FN Thomson Reuters Web of Science™
VR 1.0
PT J
AU Haddock, E
Feldmann, F
Feldmann, H
AF Haddock, Elaine
Feldmann, Friederike
Feldmann, Heinz
TI Effective Chemical Inactivation of Ebola Virus
SO EMERGING INFECTIOUS DISEASES
LA English
DT Article
ID IRRADIATION; MARBURG; LASSA
AB Reliable inactivation of specimens before removal from high-level biocontainment is crucial for safe operation. To evaluate efficacy of methods of chemical inactivation, we compared in vitro and in vivo approaches using Ebola virus as a surrogate pathogen. Consequently, we have established parameters and protocols leading to reliable and effective inactivation.
C1 [Haddock, Elaine] NIAID, Virol Lab, Div Intramural Res, NIH, Hamilton, MT USA.
[Feldmann, Friederike; Feldmann, Heinz] NIAID, NIH, Hamilton, MT USA.
RP Feldmann, H (reprint author), NIAID, Rocky Mt Labs, 903 S 4th St, Hamilton, MT 59840 USA.
EM feldmannh@niaid.nih.gov
FU NIAID at NIH
FX The study was supported by the Intramural Research Program of NIAID at
NIH.
NR 11
TC 5
Z9 5
U1 6
U2 13
PU CENTERS DISEASE CONTROL
PI ATLANTA
PA 1600 CLIFTON RD, ATLANTA, GA 30333 USA
SN 1080-6040
EI 1080-6059
J9 EMERG INFECT DIS
JI Emerg. Infect. Dis
PD JUL
PY 2016
VL 22
IS 7
BP 1292
EP 1294
DI 10.3201/eid2207.160233
PG 3
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA DP5UR
UT WOS:000378563900029
PM 27070504
ER
PT J
AU Gee, JR
Saltzstein, DR
Messing, E
Kim, K
Kolesar, J
Huang, W
Havighurst, TC
Harris, L
Wollmer, BW
Jarrard, D
House, M
Parnes, H
Bailey, HH
AF Gee, Jason R.
Saltzstein, Daniel R.
Messing, Edward
Kim, KyungMann
Kolesar, Jill
Huang, Wei
Havighurst, Thomas C.
Harris, Linda
Wollmer, Barbara W.
Jarrard, David
House, Margaret
Parnes, Howard
Bailey, Howard H.
TI Phase Ib placebo-controlled, tissue biomarker trial of diindolylmethane
(BR-DIMNG) in patients with prostate cancer who are undergoing
prostatectomy
SO EUROPEAN JOURNAL OF CANCER PREVENTION
LA English
DT Article
DE chemoprevention; diindolymethane; prostate cancer
ID AUTOMATED QUANTITATIVE-ANALYSIS; 3,3'-DIINDOLYLMETHANE; RISK;
EXPRESSION; INDOLE-3-CARBINOL; CHEMOPREVENTION; TOLERABILITY
AB Epidemiologic, preclinical, and early phase I studies of the cruciferous vegetable bioactive metabolite, 3,3-diindolylmethane (DIM), support its potential prostate cancer chemopreventive ability. We performed a multicenter, double-blind, placebo-controlled trial of DIM in patients diagnosed with prostate cancer and scheduled for radical prostatectomy. A total of 45 patients with organ-confined prostate cancer were randomized to 21-28 days of an absorption-enhanced formulation of DIM (BR-DIMNG) at doses of 100 or 200mg per os twice daily or to placebo twice daily. Prostate tissue levels of DIM were the primary endpoint, with selected secondary biomarker endpoints including blood levels of DIM, total prostate-specific antigen, testosterone, and the insulin-like growth factor-1:insulin-like growth factor binding protein-3 ratio and the urinary 2-hydroxyestrone/16-hydroxyestrone ratio, obtained at baseline, at day 15, and before surgery, as well as tissue expression of androgen receptor, prostate-specific antigen, Ki67, caspase 3 with cytochrome p450 mRNA expression and genotyping (polymorphisms). DIM was well tolerated with excellent study compliance and relatively rapid accrual of all 45 patients within 1 year. DIM levels were detected in only seven of 28 prostate tissue specimens. There was a statistically significant difference in the change in the urinary 2-hydroxyestrone/16-hydroxyestrone ratio from baseline until before surgery between the placebo and 400mg DIM groups, with otherwise statistically nonsignificant changes in plasma biomarker expression. The administration of BR-DIMNG to prostate cancer patients before prostatectomy yields detectable plasma levels but without consistent or significant tissue accumulation or biomarker modulation. This study demonstrates the feasibility of biologic evaluation of relatively nontoxic preventive agents in the preprostatectomy setting with the potential for rapid accrual.
C1 [Gee, Jason R.; Kim, KyungMann; Kolesar, Jill; Huang, Wei; Havighurst, Thomas C.; Harris, Linda; Wollmer, Barbara W.; Jarrard, David; Bailey, Howard H.] Univ Wisconsin, Carbone Canc Ctr, Madison, WI USA.
[Saltzstein, Daniel R.] Urol San Antonio Res, San Antonio, TX USA.
[Messing, Edward] Univ Rochester, Med Ctr, Rochester, NY 14642 USA.
[House, Margaret; Parnes, Howard] NCI, Div Canc Prevent, NIH, Bethesda, MD 20892 USA.
RP Gee, JR (reprint author), Lahey Clin Med Ctr, Inst Urol, 41 Mall Rd, Burlington, MA 01805 USA.
EM jason.r.gee@lahey.org
FU NCI [N01 CN35153, P30 CA014520]; NCATS [UL1TR000427]
FX This work is supported by NCI awards N01 CN35153 and P30 CA014520; and
NCATS award UL1TR000427.
NR 23
TC 1
Z9 1
U1 2
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0959-8278
EI 1473-5709
J9 EUR J CANCER PREV
JI Eur. J. Cancer Prev.
PD JUL
PY 2016
VL 25
IS 4
BP 312
EP 320
DI 10.1097/CEJ.0000000000000189
PG 9
WC Oncology
SC Oncology
GA DP6RK
UT WOS:000378625900009
PM 26313229
ER
PT J
AU Boffetta, P
Hayes, RB
Sartori, S
Lee, YCA
Muscat, J
Olshan, A
Winn, DM
Castellsague, X
Zhang, ZF
Morgenstern, H
Chen, C
Schwartz, SM
Vaughan, TL
Wunsch, V
Purdue, M
Koifman, S
Curado, MP
Vilensky, M
Gillison, M
Fernandez, L
Menezes, A
Daudt, AW
Schantz, S
Yu, GP
D'Souza, G
Haddad, RI
La Vecchia, C
Hashibe, M
AF Boffetta, Paolo
Hayes, Richard B.
Sartori, Samantha
Lee, Yuan-Chin A.
Muscat, Joshua
Olshan, Andrew
Winn, Deborah M.
Castellsague, Xavier
Zhang, Zuo-Feng
Morgenstern, Hal
Chen, Chu
Schwartz, Stephen M.
Vaughan, Thomas L.
Wunsch-Filho, Victor
Purdue, Mark
Koifman, Sergio
Curado, Maria P.
Vilensky, Marta
Gillison, Maura
Fernandez, Leticia
Menezes, Ana
Daudt, Alexander W.
Schantz, Stimson
Yu, Guopei
D'Souza, Gypsyamber
Haddad, Robert I.
La Vecchia, Carlo
Hashibe, Mia
TI Mouthwash use and cancer of the head and neck: a pooled analysis from
the International Head and Neck Cancer Epidemiology Consortium
SO EUROPEAN JOURNAL OF CANCER PREVENTION
LA English
DT Article
DE alcohol; head and neck cancer; laryngeal cancer; mouthwash; oral cancer;
pharyngeal cancer
ID UPPER AERODIGESTIVE TRACT; SQUAMOUS-CELL CARCINOMA; ORAL-CANCER;
HUMAN-PAPILLOMAVIRUS; RISK-FACTORS; OROPHARYNX; ESOPHAGUS; HEALTH
AB Most mouthwashes contain alcohol, a known cause of head and neck cancer (oral cavity, pharynx, larynx), likely through the carcinogenic activity of acetaldehyde, formed in the oral cavity from alcohol. We carried out a pooled analysis of 8981 cases of head and neck cancer and 10090 controls from 12 case-control studies with comparable information on mouthwash use in the International Head and Neck Cancer Epidemiology Consortium. Logistic regression was used to assess the association of mouthwash use with cancers of the oral cavity, oropharynx, hypopharynx, and larynx, adjusting for study, age, sex, pack-years of tobacco smoking, number of alcoholic drinks/day, and education. Compared with never users of mouthwash, the odds ratio (OR) of all head and neck cancers was 1.01 [95% confidence interval (CI): 0.94-1.08] for ever users, based on 12 studies. The corresponding ORs of cancer of the oral cavity and oropharynx were 1.11 (95% CI: 1.00-1.23) and 1.28 (95% CI: 1.06-1.56), respectively. OR for all head and neck cancer was 1.15 (95% CI: 1.01-1.30) for use for more than 35 years, based on seven studies (P for linear trend=0.01), and OR 1.31 (95% CI: 1.09-1.58) for use more than one per day, based on five studies (P for linear trend <0.001). Although limited by the retrospective nature of the study and the limited ability to assess risks of mouthwash use in nonusers of tobacco and alcohol, this large investigation shows potential risks for head and neck cancer subsites and in long-term and frequent users of mouthwash. This pooled analysis provides the most precise estimate of the association between mouthwash use and head and neck cancer.
C1 [Boffetta, Paolo; Sartori, Samantha] Icahn Sch Med Mt Sinai, Tisch Canc Inst, New York, NY 10029 USA.
[Boffetta, Paolo; Sartori, Samantha] Icahn Sch Med Mt Sinai, Inst Translat Epidemiol, New York, NY 10029 USA.
[Hayes, Richard B.] NYU, Sch Med, Div Epidemiol, Dept Populat Hlth, New York, NY USA.
[Schantz, Stimson] New York Eye & Ear Infirm, New York, NY USA.
[Lee, Yuan-Chin A.; Hashibe, Mia] Univ Utah, Sch Med, Huntsman Canc Inst, Dept Family & Prevent Med,Div Publ Hlth, Salt Lake City, UT USA.
[Muscat, Joshua] Penn State Coll Med, Hershey, PA USA.
[Olshan, Andrew] Univ N Carolina, Sch Publ Hlth, Chapel Hill, NC USA.
[Winn, Deborah M.; Purdue, Mark] NCI, Bethesda, MD 20892 USA.
[Gillison, Maura] Johns Hopkins Med Inst, Baltimore, MD USA.
[D'Souza, Gypsyamber] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA.
[Zhang, Zuo-Feng] Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA.
[Morgenstern, Hal] Univ Michigan, Sch Publ Hlth, Dept Epidemiol & Environm Hlth Sci, Ann Arbor, MI 48109 USA.
[Morgenstern, Hal] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA.
[Chen, Chu; Schwartz, Stephen M.; Vaughan, Thomas L.] Fred Hutchinson Canc Res Ctr, Seattle, WA USA.
[Haddad, Robert I.] Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA.
[Castellsague, Xavier] Hosp Llobregat, Catalan Inst Oncol ICO IDIBELL, Barcelona, Spain.
[Castellsague, Xavier] Consortium Biomed Res Epidemiol & Publ Hlth CIBER, Barcelona, Spain.
[Wunsch-Filho, Victor] Univ Sao Paulo, Sao Paulo, Brazil.
[Koifman, Sergio] Fundacao Oswaldo Cruz, Natl Sch Publ Hlth, Rio De Janeiro, Brazil.
[Menezes, Ana] Univ Fed Pelotas, Pelotas, Brazil.
[Daudt, Alexander W.] Hosp Clin Porto Alegre, Porto Alegre, RS, Brazil.
[Curado, Maria P.] Int Prevent Res Inst, Lyon, France.
[Vilensky, Marta] Univ Buenos Aires, Inst Oncol Angel H Roffo, Buenos Aires, DF, Argentina.
[Fernandez, Leticia] Inst Oncol & Radiobiol, Havana, Cuba.
[Yu, Guopei] Peking Univ, Med Informat Ctr, Beijing 100871, Peoples R China.
[La Vecchia, Carlo] Univ Milan, Dept Clin Sci & Community Hlth, Milan, Italy.
RP Boffetta, P (reprint author), Icahn Sch Med Mt Sinai, Tisch Canc Inst, New York, NY 10029 USA.
EM paolo.boffetta@mssm.edu
RI Castellsague Pique, Xavier/N-5795-2014; Kowalski, Luiz/D-1701-2012;
Menezes, Ana/G-7266-2012; Curado, Maria Paula/M-6200-2013;
OI Castellsague Pique, Xavier/0000-0002-0802-3595; Kowalski,
Luiz/0000-0001-5865-9308; Curado, Maria Paula/0000-0001-8172-2483; La
Vecchia, Carlo/0000-0003-1441-897X; Hayes, Richard/0000-0002-0918-661X
FU NIH [NCI R03CA113157, NIDCR R03DE016611, P01CA068384 K07CA104231,
R01CA048996, R01DE012609, R01CA061188, P50CA090388, R01DA011386,
R03CA077954, T32CA 009142, U01CA096134, R21ES011667, R01CA051845,
DE016631]; National Institute of Environmental Health Sciences
[P30ES010126]; Alper Research Program for Environmental Genomics of the
UCLA Jonsson Comprehensive Cancer Center; National Institutes of Health
(NCI) US; NIDCR; Fondo para la Investigacion Cientifica y Tecnologica
(FONCYT) Argentina; IMIM (Barcelona); Fundaco de Amparo a' Pesquisa no
Estado de Sao Paulo (FAPESP) [01/01768-2]; European Commission
[IC18-CT97-0222]; Fondo de Investigaciones Sanitarias (FIS) of the
Spanish Government [FIS 97/0024, FIS 97/0662, BAE 01/5013];
International Union Against Cancer (UICC); Yamagiwa-Yoshida Memorial
International Cancer Study Grant; NCI, NIH, United States; Johns Hopkins
Richard Gelb Cancer Prevention Award
FX The INHANCE Consortium was supported by NIH grants NCI R03CA113157 and
NIDCR R03DE016611. Studies participating in the pooled analysis were
supported by grants: New York multicenter: NIH [P01CA068384
K07CA104231]; Seattle (1985-1995): NIH [R01CA048996, R01DE012609]; North
Carolina (1994-1997): NIH [R01CA061188], and in part by a grant from the
National Institute of Environmental Health Sciences [P30ES010126]; Los
Angeles: NIH [P50CA090388, R01DA011386, R03CA077954, T32CA 009142,
U01CA096134, R21ES011667] and the Alper Research Program for
Environmental Genomics of the UCLA Jonsson Comprehensive Cancer Center;
Puerto Rico: jointly funded by National Institutes of Health (NCI) US
and NIDCR intramural programs; Latin America: Fondo para la
Investigacion Cientifica y Tecnologica (FONCYT) Argentina, IMIM
(Barcelona), Fundaco de Amparo a' Pesquisa no Estado de Sao Paulo
(FAPESP) [No 01/01768-2], and European Commission [IC18-CT97-0222]; IARC
Multicenter: Fondo de Investigaciones Sanitarias (FIS) of the Spanish
Government [FIS 97/0024, FIS 97/0662, BAE 01/5013], International Union
Against Cancer (UICC), and Yamagiwa-Yoshida Memorial International
Cancer Study Grant; US multicenter: The Intramural Program of the NCI,
NIH, United States; MSKCC: NIH [R01CA051845]; Baltimore: NIH [DE016631];
Hotspot: Johns Hopkins Richard Gelb Cancer Prevention Award.
NR 21
TC 0
Z9 1
U1 6
U2 9
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0959-8278
EI 1473-5709
J9 EUR J CANCER PREV
JI Eur. J. Cancer Prev.
PD JUL
PY 2016
VL 25
IS 4
BP 344
EP 348
DI 10.1097/CEJ.0000000000000179
PG 5
WC Oncology
SC Oncology
GA DP6RK
UT WOS:000378625900013
PM 26275006
ER
PT J
AU Nager, CW
Zyczynski, H
Rogers, RG
Barber, MD
Richter, HE
Visco, AG
Rardin, CR
Harvie, H
Wallace, D
Meikle, SF
AF Nager, Charles W.
Zyczynski, Halina
Rogers, Rebecca G.
Barber, Matthew D.
Richter, Holly E.
Visco, Anthony G.
Rardin, Charles R.
Harvie, Heidi
Wallace, Dennis
Meikle, Susan F.
CA Pelvic Floor Disorders Network
TI The Design of a Randomized Trial of Vaginal Surgery for Uterovaginal
Prolapse: Vaginal Hysterectomy With Native Tissue Vault Suspension
Versus Mesh Hysteropexy Suspension (The Study of Uterine Prolapse
Procedures Randomized Trial)
SO FEMALE PELVIC MEDICINE AND RECONSTRUCTIVE SURGERY
LA English
DT Article
DE vaginal surgery; hysterectomy; vaginal hysterectomy; hysteropexy; mesh;
mesh hysteropexy; randomized controlled trial; prolapse; uterovaginal
prolapse; prolapse surgery
ID PELVIC ORGAN PROLAPSE; QUALITY-OF-LIFE; UNITED-STATES; SACROSPINOUS
HYSTEROPEXY; RECONSTRUCTIVE SURGERY; URINARY-INCONTINENCE; SYNTHETIC
MESH; WOMEN; OUTCOMES; REPAIR
AB Objectives: We present the rationale for and design of a randomized controlled superiority trial comparing 2 vaginal surgical approaches for the treatment of uterovaginal prolapse. The Study of Uterine Prolapse Procedures Randomized Trial (SUPeR) trial compares the efficacy and safety of native tissue repair with vaginal hysterectomy and suture apical suspension versus uterine conservation with mesh hysteropexy through 36 to 60 months postoperatively for primary repair of uterovaginal prolapse.
Methods: The selection of the primary outcome measure, timing of randomization, patient and evaluator masking to surgical intervention, collection and adjudication of adverse events, cost effectiveness evaluations, partnering with industry, and surgeon certification of competency to perform the 2 procedures is described. A composite primary outcome of success defined as no prolapse symptoms, no objective prolapse beyond the hymen, and no retreatment of prolapse, with a minimum of 36 months postsurgery follow-up using survival analyses is planned. Secondary outcomes measured at baseline and every 6 months postsurgery include validated condition-specific and general quality of life assessments, global impression of improvement, body image, and sexual function measures. Unique challenges during the trial design include maintenance of patient masking to the intervention with routine gynecologic health maintenance and maintenance of evaluator masking.
Results: Recruitment and randomization of 180 participants is complete, and participants are currently in the follow-up phase.
Conclusions: This trial will provide information to help surgeons counsel patients and contribute evidence-based information regarding risks and benefits of 2 approaches for the treatment of uterovaginal prolapse.
C1 [Nager, Charles W.] UC San Diego Hlth Care Syst, Dept Reprod Med, San Diego, CA USA.
[Zyczynski, Halina] Univ Pittsburgh, Magee Womens Res Inst, Dept Obstet & Gynecol & Reprod Sci, Pittsburgh, PA USA.
[Rogers, Rebecca G.] Univ New Mexico, Med Ctr, Dept Obstet & Gynecol, Albuquerque, NM 87131 USA.
[Rogers, Rebecca G.] Univ New Mexico, Med Ctr, Dept Surg, Albuquerque, NM 87131 USA.
[Barber, Matthew D.] Cleveland Clin, Obstet Gynecol & Womens Hlth Inst, Cleveland, OH 44106 USA.
[Richter, Holly E.] Univ Alabama Birmingham, Dept Obstet & Gynecol, Birmingham, AL 35294 USA.
[Visco, Anthony G.] Duke Univ, Med Ctr, Dept Obstet & Gynecol, Durham, NC 27710 USA.
[Rardin, Charles R.] Brown Univ, Womens & Infants Hosp, Warren Alpert Med Sch, Dept Obstet & Gynecol, Providence, RI 02912 USA.
[Harvie, Heidi] Hosp Univ Penn, Dept Obstet & Gynecol, 3400 Spruce St, Philadelphia, PA 19104 USA.
[Wallace, Dennis] RTI Int, Res Triangle Pk, NC USA.
[Meikle, Susan F.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Gynecol Hlth & Dis Branch, NIH, Bethesda, MD USA.
RP Nager, CW (reprint author), UC San Diego Hlth Syst, 200 W Arbor Dr 8433, San Diego, CA 92103 USA.
EM cnager@ucsd.edu
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development [HD054214, HD069031, HD054215, HD069025, HD041261, HD041267,
HD069006, HD069013, HD069010]; National Institutes of Health Office of
Research on Women's Health; Boston Scientific Corporation through the
Pelvic Floor Disorders Network Data Coordinating Center
FX Supported by the Eunice Kennedy Shriver National Institute of Child
Health and Human Development grants HD054214, HD069031, HD054215,
HD069025, HD041261, HD041267, HD069006, HD069013, HD069010, and the
National Institutes of Health Office of Research on Women's Health.
Partial support for the PFDN SUPeR trial is being supplied by Boston
Scientific Corporation through an investigator initiated grant to Dr.
Wallace through the Pelvic Floor Disorders Network Data Coordinating
Center.
NR 39
TC 3
Z9 3
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 2151-8378
EI 2154-4212
J9 FEMALE PELVIC MED RE
JI Female Pelvic Med. Reconstr. Surg.
PD JUL-AUG
PY 2016
VL 22
IS 4
BP 182
EP 189
DI 10.1097/SPV.0000000000000270
PG 8
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA DP7XT
UT WOS:000378713200002
PM 27054798
ER
PT J
AU Van Dyke, ME
Drozdovitch, V
Doody, MM
Lim, H
Bolus, NE
Simon, SL
Alexander, BH
Kitahara, CM
AF Van Dyke, Miriam E.
Drozdovitch, Vladimir
Doody, Michele M.
Lim, Hyeyeun
Bolus, Norman E.
Simon, Steven L.
Alexander, Bruce H.
Kitahara, Cari M.
TI Historical Patterns in the Types of Procedures Performed and Radiation
Safety Practices Used in Nuclear Medicine From 1945-2009
SO HEALTH PHYSICS
LA English
DT Article
DE exposure; occupational; nuclear medicine; radiation protection;
radionuclide
ID RADIOLOGIC TECHNOLOGISTS; IONIZING-RADIATION; UNITED-STATES; CIRCULATORY
DISEASE; MORTALITY; CANCER; RISKS; EXPOSURE; WORKERS; COHORT
AB The authors evaluated historical patterns in the types of procedures performed in diagnostic and therapeutic nuclear medicine and the associated radiation safety practices used from 1945-2009 in a sample of U.S. radiologic technologists. In 2013-2014, 4,406 participants from the U.S. Radiologic Technologists (USRT) Study who previously reported working with medical radionuclides completed a detailed survey inquiring about the performance of 23 diagnostic and therapeutic radionuclide procedures and the use of radiation safety practices when performing radionuclide procedure-related tasks during five time periods: 1945-1964, 1965-1979, 1980-1989, 1990-1999, and 2000-2009. An overall increase in the proportion of technologists who performed specific diagnostic or therapeutic procedures was observed across the five time periods. Between 1945-1964 and 2000-2009, the median frequency of diagnostic procedures performed substantially increased (from 5 wk(-1) to 30 wk(-1)), attributable mainly to an increasing frequency of cardiac and non-brain PET scans, while the median frequency of therapeutic procedures performed modestly decreased (from 4 mo(-1) to 3 mo(-1)). Also a notable increase was observed in the use of most radiation safety practices from 1945-1964 to 2000-2009 (e.g., use of lead-shielded vials during diagnostic radiopharmaceutical preparation increased from 56 to 96%), although lead apron use dramatically decreased (e.g., during diagnostic imaging procedures, from 81 to 7%). These data describe historical practices in nuclear medicine and can be used to support studies of health risks for nuclear medicine technologists.
C1 [Van Dyke, Miriam E.; Drozdovitch, Vladimir; Doody, Michele M.; Lim, Hyeyeun; Simon, Steven L.; Kitahara, Cari M.] NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Bolus, Norman E.] Univ Alabama Birmingham, Dept Clin & Diagnost Sci, Sch Hlth Profess, Birmingham, AL USA.
[Alexander, Bruce H.] Univ Minnesota, Sch Publ Hlth, Div Environm Hlth Sci, Minneapolis, MN USA.
RP Kitahara, CM (reprint author), NCI, 9609 Med Ctr Dr, Rockville, MD 20850 USA.
EM meinholdc@mail.nih.gov
RI Kitahara, Cari/R-8267-2016
FU Division of Cancer Epidemiology and Genetics of the National Cancer
Institute
FX We thank the participants of the U.S. Radiologic Technologists Study,
Jerry Reid of the American Registry of Radiologic Technologists for
continued support, Diane Kampa and Allison Iwan of the University of
Minnesota for study management and data collection, and Jeremy Miller of
Information Management Services for data preparation. This work was
supported by the Intramural Research Program of the Division of Cancer
Epidemiology and Genetics of the National Cancer Institute.
NR 24
TC 0
Z9 0
U1 1
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0017-9078
EI 1538-5159
J9 HEALTH PHYS
JI Health Phys.
PD JUL
PY 2016
VL 111
IS 1
BP 37
EP 46
DI 10.1097/HP.0000000000000519
PG 10
WC Environmental Sciences; Public, Environmental & Occupational Health;
Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical
Imaging
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health; Nuclear Science & Technology; Radiology, Nuclear Medicine &
Medical Imaging
GA DP3XM
UT WOS:000378429300006
PM 27218293
ER
PT J
AU Canepa, M
Pozios, I
Vianello, PF
Ameri, P
Brunelli, C
Ferrucci, L
Abraham, TP
AF Canepa, Marco
Pozios, Iraklis
Vianello, Pier Filippo
Ameri, Pietro
Brunelli, Claudio
Ferrucci, Luigi
Abraham, Theodore P.
TI Distinguishing ventricular septal bulge versus hypertrophic
cardiomyopathy in the elderly
SO HEART
LA English
DT Review
ID CARDIOVASCULAR MAGNETIC-RESONANCE; OUTFLOW TRACT OBSTRUCTION; CLINICAL
PRESENTATION; FUNCTIONAL IMPACT; TASK-FORCE; PREVALENCE;
ECHOCARDIOGRAPHY; PATTERNS; AGE; HYPERTENSION
AB The burgeoning evidence of patients diagnosed with sigmoidal hypertrophic cardiomyopathy (HCM) later in life has revived the quest for distinctive features that may help discriminate it from more benign forms of isolated septal hypertrophy often labelled ventricular septal bulge (VSB). HCM is diagnosed less frequently than VSB at older ages, with a reversed female predominance. Most patients diagnosed with HCM at older ages suffer from hypertension, similar to those with VSB. A positive family history of HCM and/or sudden cardiac death and the presence of exertional symptoms usually support HCM, though they are less likely in older patients with HCM, and poorly investigated in individuals with VSB. A more severe hypertrophy and the presence of left ventricular outflow obstruction are considered diagnostic of HCM, though stress echocardiography has not been consistently used in VSB. Mitral annulus calcification is very prevalent in both conditions, whereas a restrictive filling pattern is found in a minority of older patients with HCM. Genetic testing has low applicability in this differential diagnosis at the current time, given that a causative mutation is found in less than 10% of elderly patients with suspected HCM. Emerging imaging modalities that allow non-invasive detection of myocardial fibrosis and disarray may help, but have not been fully investigated. Nonetheless, there remains a considerable morphological overlap between the two conditions. Comprehensive studies, particularly imaging based, are warranted to offer a more evidence-based approach to elderly patients with focal septal thickening.
C1 [Canepa, Marco; Pozios, Iraklis; Abraham, Theodore P.] Johns Hopkins Hypertroph Cardiomyopathy Ctr Excel, 600 North Wolfe St,Blalock 910F, Baltimore, MD USA.
[Canepa, Marco; Vianello, Pier Filippo; Ameri, Pietro; Brunelli, Claudio] Univ Genoa, IRCCS AOU San Martino IST, Dept Internal Med, Cardiovasc Dis Unit, Genoa, Italy.
[Canepa, Marco; Ferrucci, Luigi] NIA, Translat Gerontol Branch, NIH, Baltimore, MD USA.
RP Abraham, TP (reprint author), Johns Hopkins Hypertroph Cardiomyopathy Ctr Excel, 600 North Wolfe St,Blalock 910F, Baltimore, MD USA.
EM tabraha3@jhmi.edu
NR 48
TC 2
Z9 2
U1 1
U2 1
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 1355-6037
EI 1468-201X
J9 HEART
JI Heart
PD JUL
PY 2016
VL 102
IS 14
BP 1087
EP 1094
DI 10.1136/heartjnl-2015-308764
PG 8
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA DP7ZB
UT WOS:000378716600006
PM 27122487
ER
PT J
AU Hinnebusch, BJ
Chouikha, I
Sun, YC
AF Hinnebusch, B. Joseph
Chouikha, Iman
Sun, Yi-Cheng
TI Ecological Opportunity, Evolution, and the Emergence of Flea-Borne
Plague
SO INFECTION AND IMMUNITY
LA English
DT Review
ID EARLY-PHASE TRANSMISSION; YERSINIA MURINE TOXIN; CYCLIC DI-GMP; BIOFILM
FORMATION; RCS PHOSPHORELAY; PLASMINOGEN-ACTIVATOR; INFECTIOUS-DISEASES;
ADAPTIVE EVOLUTION; ESCHERICHIA-COLI; GENOME SEQUENCES
AB The plague bacillus Yersinia pestis is unique among the pathogenic Enterobacteriaceae in utilizing an arthropod-borne transmission route. Transmission by fleabite is a recent evolutionary adaptation that followed the divergence of Y. pestis from the closely related food- and waterborne enteric pathogen Yersinia pseudotuberculosis. A combination of population genetics, comparative genomics, and investigations of Yersinia-flea interactions have disclosed the important steps in the evolution and emergence of Y. pestis as a flea-borne pathogen. Only a few genetic changes, representing both gene gain by lateral transfer and gene loss by loss-of-function mutation (pseudogenization), were fundamental to this process. The emergence of Y. pestis fits evolutionary theories that emphasize ecological opportunity in adaptive diversification and rapid emergence of new species.
C1 [Hinnebusch, B. Joseph; Chouikha, Iman] NIAID, Lab Zoonot Pathogens, Rocky Mt Labs, NIH, Hamilton, MT USA.
[Sun, Yi-Cheng] Chinese Acad Med Sci, MOH Key Lab Syst Biol Pathogens, Inst Pathogen Biol, Beijing 100730, Peoples R China.
[Sun, Yi-Cheng] Peking Union Med Coll, Beijing 100021, Peoples R China.
RP Hinnebusch, BJ (reprint author), NIAID, Lab Zoonot Pathogens, Rocky Mt Labs, NIH, Hamilton, MT USA.
EM jhinnebusch@niaid.nih.gov
FU NIH, NIAID [1 ZIA AI000796-19]; National Basic Research Program of China
(973) [2015CB554200]
FX This work was funded by NIH, NIAID (1 ZIA AI000796-19; B.J.H.), and by
the National Basic Research Program of China (973 no. 2015CB554200;
Y.-C.S.).
NR 93
TC 0
Z9 0
U1 16
U2 17
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0019-9567
EI 1098-5522
J9 INFECT IMMUN
JI Infect. Immun.
PD JUL
PY 2016
VL 84
IS 7
BP 1932
EP 1940
DI 10.1128/IAI.00188-16
PG 9
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA DP5IO
UT WOS:000378529700001
PM 27160296
ER
PT J
AU Sidana, A
Walton-Diaz, A
Truong, H
Siddiqui, MM
Miao, N
Shih, J
Mannes, A
Bratslavsky, G
Linehan, WM
Metwalli, AR
AF Sidana, Abhinav
Walton-Diaz, Annerleim
Hong Truong
Siddiqui, M. Minhaj
Miao, Ning
Shih, Johanna
Mannes, Andrew
Bratslavsky, Gennady
Linehan, W. Marston
Metwalli, Adam R.
TI Postoperative elevation in creatine kinase and its impact on renal
function in patients undergoing complex partial nephrectomy
SO INTERNATIONAL UROLOGY AND NEPHROLOGY
LA English
DT Article
DE Partial nephrectomy; Creatine kinase; Rhabdomyolysis; Renal cell cancer
ID NEPHRON-SPARING SURGERY; LITHOTOMY POSITION; SURGICAL-PATIENTS; KIDNEY
INJURY; RHABDOMYOLYSIS; FAILURE; RISK; OUTCOMES; TUMORS; COMPLICATIONS
AB To identify the risk factors associated with development of postoperative elevation of creatine kinase (CK) and study its effect on renal function in patients who underwent complex multifocal partial nephrectomy (PN).
Patients who underwent PN at National Cancer Institute between January 2007 and December 2012 were included in the study. Elevated serum CK was defined as > 2000 U/L. Kidney function was assessed using serum creatinine and estimated glomerular filtration rate (eGFR). Changes were reported as percent change from preoperative values and compared using the Wilcoxon test. Regression analysis was performed to identify the predictors of elevation in CK and decline in eGFR.
From 407 total cases, 207 had adequate CK data for analysis. Median number of tumors removed was 3 (1-70). Median peak CK was 1458 (82-36,788). Forty-two percent developed CK elevation > 2000 U/L. Factors associated with postoperative elevation of CK > 2000 were young age (p = 0.009), high BMI (p = 0.003) and operating room time (p < 0.001). Although CK > 2000 was associated with significantly greater decline in eGFR (37.4 vs. 20.3 %, p < 0.001) in immediate postoperative period, this change largely resolved to a much less clinically relevant (9.2 vs 3.3 %, p = 0.040) change after 3 months. On multivariate analysis, postoperative elevation in CK was not found to be an independent factor determining renal function at 3 months.
In our cohort, a significant proportion of patients developed CK elevations > 2000 U/L. While patients with elevated CK had more decline in eGFR in immediate postoperative period, postoperative elevations of CK did not appear to impact overall long-term renal function in patients undergoing PN.
C1 [Sidana, Abhinav; Walton-Diaz, Annerleim; Hong Truong; Siddiqui, M. Minhaj; Linehan, W. Marston; Metwalli, Adam R.] NCI, Urol Oncol Branch, NIH, 10 Ctr Dr,Rm 1-5940, Bethesda, MD 20892 USA.
[Miao, Ning; Mannes, Andrew] NIH, Dept Perioperat Med, Clin Res Ctr, Bldg 10, Bethesda, MD 20892 USA.
[Shih, Johanna] NCI, Biometr Res Branch, NIH, Bethesda, MD 20892 USA.
[Bratslavsky, Gennady] SUNY Upstate Med Univ, Dept Urol, Syracuse, NY 13210 USA.
[Siddiqui, M. Minhaj] Univ Maryland, Div Urol, Dept Surg, Sch Med, Baltimore, MD 21201 USA.
RP Metwalli, AR (reprint author), NCI, Urol Oncol Branch, NIH, 10 Ctr Dr,Rm 1-5940, Bethesda, MD 20892 USA.
EM adam.metwalli@nih.gov
FU Intramural Research Program of the NIH, National Cancer Institute,
Center for Cancer Research
FX This research was supported in part by the Intramural Research Program
of the NIH, National Cancer Institute, Center for Cancer Research.
NR 31
TC 2
Z9 2
U1 1
U2 1
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0301-1623
EI 1573-2584
J9 INT UROL NEPHROL
JI Int. Urol. Nephrol.
PD JUL
PY 2016
VL 48
IS 7
BP 1047
EP 1053
DI 10.1007/s11255-016-1284-1
PG 7
WC Urology & Nephrology
SC Urology & Nephrology
GA DQ0KV
UT WOS:000378888900006
PM 27093966
ER
PT J
AU Sato, E
Muto, J
Zhang, LJ
Adase, CA
Sanford, JA
Takahashi, T
Nakatsuji, T
Usdin, TB
Gallo, RL
AF Sato, Emi
Muto, Jun
Zhang, Ling-Juan
Adase, Christopher A.
Sanford, James A.
Takahashi, Toshiya
Nakatsuji, Teruaki
Usdin, Ted B.
Gallo, Richard L.
TI The Parathyroid Hormone Second Receptor PTH2R and its Ligand
Tuberoinfundibular Peptide of 39 Residues TIP39 Regulate Intracellular
Calcium and Influence Keratinocyte Differentiation
SO JOURNAL OF INVESTIGATIVE DERMATOLOGY
LA English
DT Article
ID TYPE-2 RECEPTOR; EXPRESSION; PROTEIN; SKIN; MICE; IDENTIFICATION;
PROLIFERATION; LOCALIZATION; INFLAMMATION; HYALURONAN
AB Genes related to the parathyroid hormone (PTH) influence cutaneous immune defense and development, but the full functions of the PTH family in cutaneous biology remain incompletely understood. In this study, we examined the expression and potential functions of the PTH second receptor (PTH2R) and its ligand, the tuberoinfundibular peptide of 39 residues (TIP39), in the skin. TIP39 and PTH2R mRNA and protein were detectable in both human and mouse skin, and in cultured keratinocytes and adipocytes. TIP39 was observed in the basal layer of human skin, whereas PTH2R was detected in the spinous to granular layer. The subcellular localization of TIP39 in keratinocytes changed during calcium-induced differentiation and shifted to colocalize with PTH2R at the membrane. The addition of recombinant TIP39 to normal human keratinocytes in culture induced an increase in intercellular calcium and triggered aspects of terminal differentiation including decreased keratin-14 and increased involucrin expression. Consistent with these observations, PTH2R(-/-) ice were observed to have increased epidermal thickness. In summary, identification of TIP39 and its receptor in the epidermis reveals an additional PTH family member that is expressed in the skin and may influence keratinocyte function.
C1 [Sato, Emi; Zhang, Ling-Juan; Adase, Christopher A.; Sanford, James A.; Takahashi, Toshiya; Nakatsuji, Teruaki; Gallo, Richard L.] Univ Calif San Diego, Dept Dermatol, 9500 Gillman, La Jolla, CA 92093 USA.
[Muto, Jun] Aichi Med Univ, Dept Dermatol, Nagakute, Aichi, Japan.
[Usdin, Ted B.] NIMH, Sect Fundamental Neurosci, Bethesda, MD 20892 USA.
RP Gallo, RL (reprint author), Univ Calif San Diego, Dept Dermatol, 9500 Gillman, La Jolla, CA 92093 USA.
EM rgallo@ucsd.edu
FU NIH [R01AI116576, R01AR064781, R01AI052453, R21AR0675478, U19AI117673,
P01HL107150]; UCSD Dermatologist Investigator Training Program
[T32AR062496]
FX This work was supported in part by NIH grants R01AI116576, R01AR064781,
R01AI052453, R21AR0675478, U19AI117673, and P01HL107150 (RLG) and the
UCSD Dermatologist Investigator Training Program T32AR062496 (JAS, CA).
NR 46
TC 0
Z9 0
U1 0
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0022-202X
EI 1523-1747
J9 J INVEST DERMATOL
JI J. Invest. Dermatol.
PD JUL
PY 2016
VL 136
IS 7
BP 1449
EP 1459
DI 10.1016/j.jid.2016.02.814
PG 11
WC Dermatology
SC Dermatology
GA DQ2FA
UT WOS:000379016400022
PM 27000502
ER
PT J
AU van Leeuwen, EM
Sabo, A
Bis, JC
Huffman, JE
Manichaikul, A
Smith, AV
Feitosa, MF
Demissie, S
Joshi, PK
Duan, Q
Marten, J
van Klinken, JB
Surakka, I
Nolte, IM
Zhang, WH
Mbarek, H
Li-Gao, RF
Trompet, S
Verweij, N
Evangelou, E
Lyytikainen, LP
Tayo, BO
Deelen, J
van der Most, PJ
van der Laan, SW
Arking, DE
Morrison, A
Dehghan, A
Franco, OH
Hofman, A
Rivadeneira, F
Sijbrands, EJ
Uitterlinden, AG
Mychaleckyj, JC
Campbell, A
Hocking, LJ
Padmanabhan, S
Brody, JA
Rice, KM
White, CC
Harris, T
Isaacs, A
Campbell, H
Lange, LA
Rudan, I
Kolcic, I
Navarro, P
Zemunik, T
Salomaa, V
Kooner, AS
Kooner, JS
Lehne, B
Scott, WR
Tan, ST
de Geus, EJ
Milaneschi, Y
Penninx, BWJH
Willemsen, G
de Mutsert, R
Ford, I
Gansevoort, RT
Segura-Lepe, MP
Raitakari, OT
Viikari, JS
Nikus, K
Forrester, T
McKenzie, CA
de Craen, AJM
de Ruijter, HM
Pasterkamp, G
Snieder, H
Oldehinkel, AJ
Slagboom, PE
Cooper, RS
Kahonen, M
Lehtimaki, T
Elliott, P
van der Harst, P
Jukema, JW
Mook-Kanamori, DO
Boomsma, DI
Chambers, JC
Swertz, M
Ripatti, S
van Dijk, KW
Vitart, V
Polasek, O
Hayward, C
Wilson, JG
Wilson, JF
Gudnason, V
Rich, SS
Psaty, BM
Borecki, IB
Boerwinkle, E
Rotter, JI
Cupples, LA
van Duijn, CM
AF van Leeuwen, Elisabeth M.
Sabo, Aniko
Bis, Joshua C.
Huffman, Jennifer E.
Manichaikul, Ani
Smith, Albert V.
Feitosa, Mary F.
Demissie, Serkalem
Joshi, Peter K.
Duan, Qing
Marten, Jonathan
van Klinken, Jan B.
Surakka, Ida
Nolte, Ilja M.
Zhang, Weihua
Mbarek, Hamdi
Li-Gao, Ruifang
Trompet, Stella
Verweij, Niek
Evangelou, Evangelos
Lyytikainen, Leo-Pekka
Tayo, Bamidele O.
Deelen, Joris
van der Most, Peter J.
van der Laan, Sander W.
Arking, Dan E.
Morrison, Alanna
Dehghan, Abbas
Franco, Oscar H.
Hofman, Albert
Rivadeneira, Fernando
Sijbrands, Eric J.
Uitterlinden, Andre G.
Mychaleckyj, Josyf C.
Campbell, Archie
Hocking, Lynne J.
Padmanabhan, Sandosh
Brody, Jennifer A.
Rice, Kenneth M.
White, Charles C.
Harris, Tamara
Isaacs, Aaron
Campbell, Harry
Lange, Leslie A.
Rudan, Igor
Kolcic, Ivana
Navarro, Pau
Zemunik, Tatijana
Salomaa, Veikko
Kooner, Angad S.
Kooner, Jaspal S.
Lehne, Benjamin
Scott, William R.
Tan, Sian-Tsung
de Geus, Eco J.
Milaneschi, Yuri
Penninx, Brenda W. J. H.
Willemsen, Gonneke
de Mutsert, Renee
Ford, Ian
Gansevoort, Ron T.
Segura-Lepe, Marcelo P.
Raitakari, Olli T.
Viikari, Jorma S.
Nikus, Kjell
Forrester, Terrence
McKenzie, Colin A.
de Craen, Anton J. M.
de Ruijter, Hester M.
Pasterkamp, Gerard
Snieder, Harold
Oldehinkel, Albertine J.
Slagboom, P. Eline
Cooper, Richard S.
Kahonen, Mika
Lehtimaki, Terho
Elliott, Paul
van der Harst, Pim
Jukema, J. Wouter
Mook-Kanamori, Dennis O.
Boomsma, Dorret I.
Chambers, John C.
Swertz, Morris
Ripatti, Samuli
van Dijk, Ko Willems
Vitart, Veronique
Polasek, Ozren
Hayward, Caroline
Wilson, James G.
Wilson, James F.
Gudnason, Vilmundur
Rich, Stephen S.
Psaty, Bruce M.
Borecki, Ingrid B.
Boerwinkle, Eric
Rotter, Jerome I.
Cupples, L. Adrienne
van Duijn, Cornelia M.
CA CHARGE Lipids Working Grp
TI Meta-analysis of 49 549 individuals imputed with the 1000 Genomes
Project reveals an exonic damaging variant in ANGPTL4 determining
fasting TG levels
SO JOURNAL OF MEDICAL GENETICS
LA English
DT Article
ID ELEMENT-BINDING PROTEIN; GENE-EXPRESSION; LIPID-SYNTHESIS; GLUCOSE;
CHREBP; MUTATIONS; TRIGLYCERIDES; TRANSCRIPTION; SREBP-1C; DISEASE
AB Background So far, more than 170 loci have been associated with circulating lipid levels through genome-wide association studies (GWAS). These associations are largely driven by common variants, their function is often not known, and many are likely to be markers for the causal variants. In this study we aimed to identify more new rare and low-frequency functional variants associated with circulating lipid levels.
Methods We used the 1000 Genomes Project as a reference panel for the imputations of GWAS data from similar to 60 000 individuals in the discovery stage and similar to 90 000 samples in the replication stage.
Results Our study resulted in the identification of five new associations with circulating lipid levels at four loci. All four loci are within genes that can be linked biologically to lipid metabolism. One of the variants, rs116843064, is a damaging missense variant within the ANGPTL4 gene.
Conclusions This study illustrates that GWAS with high-scale imputation may still help us unravel the biological mechanism behind circulating lipid levels.
C1 [van Leeuwen, Elisabeth M.; Dehghan, Abbas; Franco, Oscar H.; Hofman, Albert; Uitterlinden, Andre G.; Isaacs, Aaron; van Duijn, Cornelia M.] Erasmus MC, Dept Epidemiol, NL-3000 CA Rotterdam, Netherlands.
[Sabo, Aniko; Boerwinkle, Eric] Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA.
[Bis, Joshua C.; Brody, Jennifer A.; Psaty, Bruce M.] Univ Washington, Dept Med, Seattle, WA USA.
[Huffman, Jennifer E.; Marten, Jonathan; Navarro, Pau; Vitart, Veronique; Hayward, Caroline; Wilson, James F.] Univ Edinburgh, Inst Genet & Mol Med, Med Res Council Human Genet Unit, Edinburgh, Midlothian, Scotland.
[Huffman, Jennifer E.; Cupples, L. Adrienne] NHLBI, Framingham Heart Study, Cardiovasc Epidemiol & Human Genom Branch, Framingham, MA USA.
[Manichaikul, Ani; Mychaleckyj, Josyf C.; Rich, Stephen S.] Univ Virginia, Ctr Publ Hlth Genom, Charlottesville, VA USA.
[Smith, Albert V.; Gudnason, Vilmundur] Iceland Heart Assoc, Kopavogur, Iceland.
[Smith, Albert V.; Gudnason, Vilmundur] Univ Iceland, Fac Med, Reykjavik, Iceland.
[Feitosa, Mary F.; Borecki, Ingrid B.; Cupples, L. Adrienne] Washington Univ, Sch Med, Dept Genet, St Louis, MO 63110 USA.
[Demissie, Serkalem] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA.
[Joshi, Peter K.; Campbell, Harry; Wilson, James F.] Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Edinburgh, Midlothian, Scotland.
Univ N Carolina, Dept Genet, Chapel Hill, NC USA.
[van Klinken, Jan B.; van Dijk, Ko Willems] Leiden Univ, Med Ctr, Dept Human Genet, Leiden, Netherlands.
[Surakka, Ida; Ripatti, Samuli] Univ Helsinki, Inst Mol Med, Human Genom Unit, Helsinki, Finland.
[Nolte, Ilja M.; van der Most, Peter J.; Snieder, Harold] Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, Groningen, Netherlands.
[Zhang, Weihua; Evangelou, Evangelos; Lehne, Benjamin; Scott, William R.; Segura-Lepe, Marcelo P.; Chambers, John C.] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England.
[Zhang, Weihua; Kooner, Jaspal S.; Scott, William R.; Chambers, John C.] Ealing Hosp NHS Trust, Dept Cardiol, Southall, Middx, England.
[Mbarek, Hamdi; de Geus, Eco J.; Willemsen, Gonneke; Boomsma, Dorret I.] Vrije Univ Amsterdam, Dept Biol Psychol, Amsterdam, Netherlands.
[Mbarek, Hamdi; de Geus, Eco J.; Willemsen, Gonneke; Boomsma, Dorret I.] EMGO Inst Hlth & Care Res, Amsterdam, Netherlands.
[Li-Gao, Ruifang; de Mutsert, Renee; Mook-Kanamori, Dennis O.] Leiden Univ, Med Ctr, Dept Clin Epidemiol, Leiden, Netherlands.
[Trompet, Stella; Jukema, J. Wouter] Leiden Univ, Med Ctr, Dept Cardiol, Leiden, Netherlands.
[Trompet, Stella; de Craen, Anton J. M.] Leiden Univ, Med Ctr, Dept Gerontol & Geriatr, Leiden, Netherlands.
[Verweij, Niek; van der Harst, Pim] Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, Groningen, Netherlands.
[Evangelou, Evangelos] Univ Ioannina, Sch Med, Dept Hyg & Epidemiol, GR-45110 Ioannina, Greece.
[Lyytikainen, Leo-Pekka; Lehtimaki, Terho] Fimlab Labs, Dept Clin Chem, Tampere, Finland.
[Lyytikainen, Leo-Pekka; Lehtimaki, Terho] Univ Tampere, Sch Med, Dept Clin Chem, FIN-33101 Tampere, Finland.
[Tayo, Bamidele O.; Cooper, Richard S.] Loyola Univ, Chicago Stritch Sch Med, Publ Hlth Sci, Maywood, IL 60153 USA.
[Deelen, Joris; Slagboom, P. Eline] Leiden Univ, Med Ctr, Dept Mol Epidemiol, Leiden, Netherlands.
[van der Laan, Sander W.; de Ruijter, Hester M.; Pasterkamp, Gerard] Univ Med Ctr Utrecht, Lab Expt Cardiol, Utrecht, Netherlands.
[Arking, Dan E.] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD USA.
[Morrison, Alanna; Boerwinkle, Eric] Univ Texas Houston, Sch Publ Hlth, Ctr Human Genet, Houston, TX USA.
[Rivadeneira, Fernando; Sijbrands, Eric J.; Uitterlinden, Andre G.] Erasmus MC, Dept Internal Med, Rotterdam, Netherlands.
[Campbell, Archie] Univ Edinburgh, Inst Genet & Mol Med, Ctr Genom & Expt Med, Generat Scotland, Edinburgh, Midlothian, Scotland.
[Hocking, Lynne J.] Univ Aberdeen, Div Appl Med, Musculoskeletal Res Programme, Aberdeen, Scotland.
[Padmanabhan, Sandosh] Univ Glasgow, British Heart Fdn Glasgow Cardiovasc Res Ctr, Inst Cardiovasc & Med Sci, Coll Med Vet & Life Sci, Glasgow, Lanark, Scotland.
[Rice, Kenneth M.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
[White, Charles C.] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA.
[Harris, Tamara] NIA, Lab Epidemiol & Populat Sci, NIH, Bethesda, MD 20892 USA.
[Rudan, Igor] Univ Edinburgh, Ctr Populat Hlth Sci, Edinburgh, Midlothian, Scotland.
[Kolcic, Ivana; Zemunik, Tatijana; Polasek, Ozren] Univ Split, Fac Med, Split, Croatia.
[Salomaa, Veikko] Natl Inst Hlth & Welf, Dept Hlth, Helsinki, Finland.
[Kooner, Angad S.; Kooner, Jaspal S.; Tan, Sian-Tsung] Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, Cardiovasc Sci, London, England.
[Kooner, Jaspal S.; Chambers, John C.] Univ London Imperial Coll Sci Technol & Med, Imperial Coll Healthcare NHS Trus, London, England.
[Milaneschi, Yuri; Penninx, Brenda W. J. H.] Vrije Univ Amsterdam, Med Ctr Amsterdam GGZinGeest, Dept Psychiat, Amsterdam, Netherlands.
[Milaneschi, Yuri; Penninx, Brenda W. J. H.] EMGO Inst Hlth & Care Res & Neurosci Campus Amste, Amsterdam, Netherlands.
[Ford, Ian] Univ Glasgow, Robertson Ctr Biostat, Glasgow, Lanark, Scotland.
[Gansevoort, Ron T.] Univ Groningen, Univ Med Ctr Groningen, Dept Nephrol, Groningen, Netherlands.
[Raitakari, Olli T.] Turku Univ Hosp, Dept Clin Physiol, FIN-20520 Turku, Finland.
[Raitakari, Olli T.] Univ Turku, Res Ctr Appl & Prevent Cardiovasc Med, Turku, Finland.
[Viikari, Jorma S.] Turku Univ Hosp, Div Med, FIN-20520 Turku, Finland.
[Viikari, Jorma S.] Univ Turku, Dept Med, Turku, Finland.
[Nikus, Kjell] Tampere Univ Hosp, Heart Hosp, Dept Cardiol, Tampere, Finland.
[Nikus, Kjell] Univ Tampere, Sch Med, FIN-33101 Tampere, Finland.
[Forrester, Terrence; McKenzie, Colin A.] Univ W Indies, Res Inst Trop Med, Trop Metab Res Unit, Monaco, Jamaica.
[Pasterkamp, Gerard] Univ Med Ctr Utrecht, Lab Clin Chem & Hematol, Utrecht, Netherlands.
[Oldehinkel, Albertine J.] Univ Groningen, Univ Med Ctr Groningen, Dept Psychiat, Groningen, Netherlands.
[Kahonen, Mika] Tampere Univ Hosp, Dept Clin Physiol, Tampere, Finland.
[Kahonen, Mika] Univ Tampere, Sch Med, Dept Clin Physiol, FIN-33101 Tampere, Finland.
[Elliott, Paul] Univ London Imperial Coll Sci Technol & Med, MRC PHE Ctr Environm & Hlth, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England.
[van der Harst, Pim; Swertz, Morris] Univ Groningen, Univ Med Ctr Groningen, Dept Genet, Groningen, Netherlands.
[Mook-Kanamori, Dennis O.] Leiden Univ, Med Ctr, Dept Publ Hlth & Primary Care, Leiden, Netherlands.
[Mook-Kanamori, Dennis O.] King Faisal Med Hosp & Res Ctr, Dept BESC, Epidemiol Sect, Riyadh, Saudi Arabia.
[Swertz, Morris] Univ Groningen, Univ Med Ctr Groningen, Genom Coordinat Ctr, Groningen, Netherlands.
[Ripatti, Samuli] Univ Helsinki, Publ Hlth, Helsinki, Finland.
[Ripatti, Samuli] Wellcome Trust Sanger Inst, Hinxton, England.
[van Dijk, Ko Willems] Leiden Univ, Med Ctr, Dept Gen Internal Med, Leiden, Netherlands.
[Wilson, James G.] Univ Mississippi, Med Ctr, Physiol & Biophys, Jackson, MS 39216 USA.
[Psaty, Bruce M.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
[Psaty, Bruce M.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA.
[Psaty, Bruce M.] Grp Hlth Res Inst, Grp Hlth Cooperat, Seattle, WA USA.
[Rotter, Jerome I.] Harbor UCLA Med Ctr, Inst Translat Genom & Populat Sci, Los Angeles BioMed Res Inst, Torrance, CA 90509 USA.
[Rotter, Jerome I.] Harbor UCLA Med Ctr, Dept Pediat, Div Genom Outcomes, Torrance, CA 90509 USA.
[Rotter, Jerome I.] Univ Calif Los Angeles, Dept Pediat, Los Angeles, CA 90024 USA.
[Rotter, Jerome I.] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA.
[Rotter, Jerome I.] Univ Calif Los Angeles, Dept Human Genet, Los Angeles, CA USA.
RP van Duijn, CM (reprint author), Erasmus MC, Dept Epidemiol, Genet Epidemiol Unit, Postbus 2040, NL-3000 CA Rotterdam, Netherlands.
EM c.vanduijn@erasmusmc.nl
RI Slagboom, P. Eline/R-4790-2016; Padmanabhan, Sandosh/S-3963-2016;
Verweij, Niek/A-4499-2017; Polasek, Ozren/B-6002-2011; Kolcic,
Ivana/E-2713-2017; Feitosa, Mary/K-8044-2012; Smith, Albert
Vernon/K-5150-2015
OI de Geus, Eco/0000-0001-6022-2666; Dehghan, Abbas/0000-0001-6403-016X;
Mbarek, Hamdi/0000-0002-1108-0371; Slagboom, P.
Eline/0000-0002-2875-4723; Manichaikul, Ani/0000-0002-5998-795X; van der
Laan, Sander W./0000-0001-6888-1404; Evangelou,
Evangelos/0000-0002-5488-2999; Polasek, Ozren/0000-0002-5765-1862;
Kolcic, Ivana/0000-0001-7918-6052; Feitosa, Mary/0000-0002-0933-2410;
Hocking, Lynne J/0000-0002-2414-2826; Verweij, Niek/0000-0002-4303-7685;
Smith, Albert Vernon/0000-0003-1942-5845
FU NIH [N01-AG-1-2100, HHSN271201200022C]; NIA Intramural Research Program;
Hjartavernd (the Icelandic Heart Association); Althingi (the Icelandic
Parliament); Home Office [780-TETRA]; National Institute for Health
Research (NIHR) Imperial College Healthcare NHS Trust (ICHNT); Imperial
College Biomedical Research Centre (BRC); ICHNT; Imperial College BRC;
MRC-PHE Centre for Environment and Health; NIHR Health Protection
Research Unit on Health Impact of Environmental Hazards; National Heart,
Lung, and Blood Institute (NHLBI) [HHSN268201100005C, HHSN268201100006C,
HHSN268201100007C, HHSN268201100008C, HHSN268201100009C,
HHSN268201100010C, HHSN268201100011C, HHSN268201100012C, R01HL087641,
R01HL59367, R01HL086694]; National Human Genome Research Institute
[U01HG004402]; National Institutes of Health [HHSN268200625226C]; NHLBI
[HHSN268201200036C, HHSN268200800007C, N01HC55222, N01HC85079,
N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086, U01HL080295,
R01HL087652, R01HL105756, R01HL103612, R01HL120393]; National Institute
on Aging (NIA) [R01AG023629]; National Center for Advancing
Translational Sciences; CTSI grant [UL1TR000124]; National Institute of
Diabetes and Digestive and Kidney Disease Diabetes Research Center (DRC)
[DK063491]; Medical Research Council UK; Croatian Ministry of Science,
Education and Sports [216-1080315-0302]; European Union
[LSHG-CT-2006-018947, 259679, 279143]; Croatian Science Foundation
[8875]; European Commission FP6 STRP grant [018947
(LSHG-CT-2006-01947)]; European Community [HEALTH-F4-2007-201413];
European Commission under the programme "Quality of Life and Management
of the Living Resources" of 5th Framework Programme
[QLG2-CT-2002-01254]; ENGAGE consortium; CMSB; Netherlands Organisation
for Scientific Research [NWO-RFBR 047.017.043]; Russian Foundation for
Basic Research [NWO-RFBR 047.017.043]; ZonMw grant [91111025]; National
Heart, Lung, and Blood Institute [R01-HL-087700, R01-HL-088215,
R01-HL-117078]; Chief Scientist Office of the Scottish Government Health
Directorate [CZD/16/6]; Scottish Funding Council [HR03006]; UK's Medical
Research Council; Netherlands Organization of Scientific Research NWO
[175.010.2007.006]; Economic Structure Enhancing Fund (FES) of the Dutch
government; Ministry of Economic Affairs; Ministry of Education, Culture
and Science; Ministry for Health, Welfare and Sports; Northern
Netherlands Collaboration of Provinces (SNN); Province of Groningen;
University Medical Center Groningen; University of Groningen; Dutch
Kidney Foundation; Dutch Diabetes Research Foundation;
Innovation-Oriented Research Program on Genomics (SenterNovem)
[IGE05007]; Centre for Medical Systems Biology; Netherlands Consortium
for Healthy Ageing [050-060-810]; UnileverColworth; BBMRI-NL, a Research
Infrastructure - Dutch government [NWO 184.021.007]; National Institute
for Health Research (NIHR) Comprehensive Biomedical Research Centre
Imperial College Healthcare NHS Trust; British Heart Foundation
[SP/04/002]; Medical Research Council [G0601966, G0700931]; Wellcome
Trust [084723/Z/08/Z]; NIHR [RP-PG-0407-10371]; Action on Hearing Loss
[G51]; Division and the Board of Directors of the Leiden University
Medical Center; Leiden University, Research Profile Area 'Vascular and
Regenerative Medicine'; Dutch Science Organization (ZonMW-VENI Grant)
[916.14.023]; Chief Scientist Office of the Scottish Government; Royal
Society; MRC Human Genetics Unit; Arthritis Research UK; Bristol-Myers
Squibb; Netherlands Heart Foundation [2001 D 032]; European commission
[223004]; Netherlands Genomics Initiative (Netherlands Consortium for
Healthy Aging) [050-060-810]; Netherlands Organisation of Scientific
Research NWO [175.010.2005.011, 911-03-012]; Research Institute for
Diseases in the Elderly [014-93-015, RIDE2]; Netherlands Genomics
Initiative (NGI)/Netherlands Organisation for Scientific Research (NWO)
[050-060-810]; Erasmus Medical Center; Erasmus University, Rotterdam;
Netherlands Organization for the Health Research and Development
(ZonMw); Research Institute for Diseases in the Elderly (RIDE); European
Commission (DG XII); Municipality of Rotterdam; University Medical
Center, Netherlands; Erasmus University Medical Center Rotterdam,
Netherlands; University of Utrecht, Netherlands; Radboud Medical Center
Nijmegen, Netherlands; Parnassia Bavo group, Netherlands; University of
Groningen, Netherlands; Netherlands Organization for Scientific Research
NWO (Medical Research Council program) [GB-MW 940-38-011]; Netherlands
Organization for Scientific Research NWO (ZonMW Brainpower grant)
[100-001-004]; ZonMw Risk Behavior and Dependence grants
[60-60600-97-118]; ZonMw Culture and Health grant [261-98-710]; Social
Sciences Council [GB-MaGW 480-01-006, GB-MaGW 480-07-001, GB-MaGW
452-04-314, GB-MaGW 452-06-004]; NWO large-sized investment grant
[175.010.2003.005]; NWO Longitudinal Survey and Panel Funding
[481-08-013, 481-11-001]; Dutch Ministry of Justice (WODC); European
Science Foundation [FP-006]; Biobanking and Biomolecular Resources
Research Infrastructure BBMRI-NL [CP 32]
FX The AGES Study has been funded by NIH contracts N01-AG-1-2100 and
HHSN271201200022C, the NIA Intramural Research Program, Hjartavernd (the
Icelandic Heart Association), and the Althingi (the Icelandic
Parliament).; The Airwave Study is funded by the Home Office (grant
number 780-TETRA) with additional support from the National Institute
for Health Research (NIHR) Imperial College Healthcare NHS Trust (ICHNT)
and Imperial College Biomedical Research Centre (BRC). PE is an NIHR
Senior Investigator and is supported by the ICHNT and Imperial College
BRC, the MRC-PHE Centre for Environment and Health and the NIHR Health
Protection Research Unit on Health Impact of Environmental Hazards.; The
ARIC Study is carried out as a collaborative study supported by National
Heart, Lung, and Blood Institute (NHLBI) contracts (HHSN268201100005C,
HHSN268201100006C, HHSN268201100007C, HHSN268201100008C,
HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, and
HHSN268201100012C), R01HL087641, R01HL59367 and R01HL086694; National
Human Genome Research Institute contract U01HG004402; and National
Institutes of Health contract HHSN268200625226C.; Cardiovascular Health
Study: This CHS research was supported by NHLBI contracts
HHSN268201200036C, HHSN268200800007C, N01HC55222, N01HC85079,
N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086; and NHLBI
grants U01HL080295, R01HL087652, R01HL105756, R01HL103612, and
R01HL120393 with additional contribution from the National Institute of
Neurological Disorders and Stroke (NINDS). Additional support was
provided through R01AG023629 from the National Institute on Aging (NIA).
A full list of principal CHS investigators and institutions can be found
at CHS-NHLBI.org. The provision of genotyping data was supported in part
by the National Center for Advancing Translational Sciences, CTSI grant
UL1TR000124, and the National Institute of Diabetes and Digestive and
Kidney Disease Diabetes Research Center (DRC) grant DK063491 to the
Southern California Diabetes Endocrinology Research Center. The content
is solely the responsibility of the authors and does not necessarily
represent the official views of the National Institutes of Health.;
CROATIA-Korcula, CROATIA-Split and CROATIA-Vis (CR-Korcula, CR-Split,
CR-Vis) were funded by the Medical Research Council UK, The Croatian
Ministry of Science, Education and Sports (grant 216-1080315-0302), the
European Union framework program 6 EUROSPAN project (contract no.
LSHG-CT-2006-018947) and the Croatian Science Foundation (grant 8875).;
The ERF study as a part of EUROSPAN (European Special Populations
Research Network) was supported by European Commission FP6 STRP grant
number 018947 (LSHG-CT-2006-01947) and also received funding from the
European Community's Seventh Framework Programme (FP7/2007-2013)/grant
agreement HEALTH-F4-2007-201413 by the European Commission under the
programme "Quality of Life and Management of the Living Resources" of
5th Framework Programme (no. QLG2-CT-2002-01254). The ERF study was
further supported by ENGAGE consortium and CMSB. High-throughput
analysis of the ERF data was supported by joint grant from Netherlands
Organisation for Scientific Research and the Russian Foundation for
Basic Research (NWO-RFBR 047.017.043). Exome sequencing in ERF was
supported by the ZonMw grant (project 91111025).; The Family Heart Study
was supported by the by grants R01-HL-087700, R01-HL-088215 and
R01-HL-117078 from the National Heart, Lung, and Blood Institute.;
Generation Scotland received core funding from the Chief Scientist
Office of the Scottish Government Health Directorate CZD/16/6 and the
Scottish Funding Council HR03006. Genotyping of the GS: SFHS samples was
carried out by the Genetics Core Laboratory at the Wellcome Trust
Clinical Research Facility, Edinburgh, Scotland and was funded by the
UK's Medical Research Council.; The LifeLines Cohort Study, and
generation and management of GWAS genotype data for the LifeLines Cohort
Study is supported by the Netherlands Organization of Scientific
Research NWO (grant 175.010.2007.006), the Economic Structure Enhancing
Fund (FES) of the Dutch government, the Ministry of Economic Affairs,
the Ministry of Education, Culture and Science, the Ministry for Health,
Welfare and Sports, the Northern Netherlands Collaboration of Provinces
(SNN), the Province of Groningen, University Medical Center Groningen,
the University of Groningen, Dutch Kidney Foundation and Dutch Diabetes
Research Foundation.; The Leiden Longevity Study (LLS) has received
funding from the European Union's Seventh Framework Programme
(FP7/2007-2011) under grant agreement no 259679. This study was
supported by a grant from the Innovation-Oriented Research Program on
Genomics (SenterNovem IGE05007), the Centre for Medical Systems Biology,
and the Netherlands Consortium for Healthy Ageing (grant 050-060-810),
all in the framework of the Netherlands Genomics Initiative, Netherlands
Organization for Scientific Research (NWO), UnileverColworth and by
BBMRI-NL, a Research Infrastructure financed by the Dutch government
(NWO 184.021.007).; The LOLIPOP study is supported by the National
Institute for Health Research (NIHR) Comprehensive Biomedical Research
Centre Imperial College Healthcare NHS Trust, the British Heart
Foundation (SP/04/002), the Medical Research Council
(G0601966,G0700931), the Wellcome Trust (084723/Z/08/Z) the NIHR
(RP-PG-0407-10371), European Union FP7 (EpiMigrant, 279143) and Action
on Hearing Loss (G51). The work was carried out in part at the
NIHR/Wellcome Trust Imperial Clinical Research Facility.; The NEO study
is supported by the participating Departments, the Division and the
Board of Directors of the Leiden University Medical Center, and by the
Leiden University, Research Profile Area 'Vascular and Regenerative
Medicine'. Dennis Mook-Kanamori is supported by Dutch Science
Organization (ZonMW-VENI Grant 916.14.023).; ORCADES was supported by
the Chief Scientist Office of the Scottish Government, the Royal
Society, the MRC Human Genetics Unit, Arthritis Research UK and the
European Union framework program 6 EUROSPAN project (contract no.
LSHG-CT-2006-018947). DNA extractions were performed at the Wellcome
Trust Clinical Research Facility in Edinburgh.; The PROSPER study was
supported by an investigator initiated grant obtained from Bristol-Myers
Squibb. JWJ is an Established Clinical Investigator of the Netherlands
Heart Foundation (grant 2001 D 032). Support for genotyping was provided
by the seventh framework program of the European commission (grant
223004) and by the Netherlands Genomics Initiative (Netherlands
Consortium for Healthy Aging grant 050-060-810).; The generation and
management of GWAS genotype data for the Rotterdam Study is supported by
the Netherlands Organisation of Scientific Research NWO Investments (nr.
175.010.2005.011, 911-03-012). This study is funded by the Research
Institute for Diseases in the Elderly (014-93-015; RIDE2), the
Netherlands Genomics Initiative (NGI)/Netherlands Organisation for
Scientific Research (NWO) project nr. 050-060-810. The Rotterdam Study
is funded by Erasmus Medical Center and Erasmus University, Rotterdam,
Netherlands Organization for the Health Research and Development
(ZonMw), the Research Institute for Diseases in the Elderly (RIDE), the
Ministry of Education, Culture and Science, the Ministry for Health,
Welfare and Sports, the European Commission (DG XII), and the
Municipality of Rotterdam.; Participating centres of TRAILS include the
University Medical Center and University of Groningen, the Erasmus
University Medical Center Rotterdam, the University of Utrecht, the
Radboud Medical Center Nijmegen, and the Parnassia Bavo group, all in
the Netherlands. TRAILS has been financially supported by various grants
from the Netherlands Organization for Scientific Research NWO (Medical
Research Council program grant GB-MW 940-38-011; ZonMW Brainpower grant
100-001-004; ZonMw Risk Behavior and Dependence grants 60-60600-97-118;
ZonMw Culture and Health grant 261-98-710; Social Sciences Council
medium-sized investment grants GB-MaGW 480-01-006 and GB-MaGW
480-07-001; Social Sciences Council project grants GB-MaGW 452-04-314
and GB-MaGW 452-06-004; NWO large-sized investment grant
175.010.2003.005; NWO Longitudinal Survey and Panel Funding 481-08-013
and 481-11-001), the Dutch Ministry of Justice (WODC), the European
Science Foundation (EuroSTRESS project FP-006), Biobanking and
Biomolecular Resources Research Infrastructure BBMRI-NL (CP 32), and the
participating universities.
NR 20
TC 1
Z9 1
U1 2
U2 6
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0022-2593
EI 1468-6244
J9 J MED GENET
JI J. Med. Genet.
PD JUL
PY 2016
VL 53
IS 7
BP 441
EP 449
DI 10.1136/jmedgenet-2015-103439
PG 9
WC Genetics & Heredity
SC Genetics & Heredity
GA DP5KH
UT WOS:000378534500003
PM 27036123
ER
PT J
AU Carr, W
Olivera, A
Harrell, M
Milhorn, D
Elliot, J
Rogers, N
Brodnick, R
Gill, J
AF Carr, Walter
Olivera, Anlys
Harrell, Misha
Milhorn, Denise
Elliot, Jonathan
Rogers, Nicholas
Brodnick, Robert
Gill, Jessica
TI AN EVALUATION OF ACUTE NEUROTRAUMA BIOMARKERS IN SERUM FOR CONCUSSED AND
NON-CONCUSSED COMBAT ZONE COHORTS
SO JOURNAL OF NEUROTRAUMA
LA English
DT Meeting Abstract
CT 34th Annual National Neurotrauma Symposium
CY JUN 26-29, 2016
CL Lexington, KY
DE military; acute; serum; UCH-L1
C1 [Carr, Walter] USAMRMC, Ft Detrick, MD USA.
[Olivera, Anlys; Gill, Jessica] NINR, NIH, Bethesda, MD 20892 USA.
[Harrell, Misha] 651st EAES, Camp Leatherneck, Afghanistan.
[Carr, Walter; Milhorn, Denise; Elliot, Jonathan; Rogers, Nicholas; Brodnick, Robert] 1st MLG Fwd, Camp Leatherneck, Afghanistan.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 0897-7151
EI 1557-9042
J9 J NEUROTRAUM
JI J. Neurotrauma
PD JUL 1
PY 2016
VL 33
IS 13
MA PSB-240
BP A99
EP A99
PG 1
WC Critical Care Medicine; Clinical Neurology; Neurosciences
SC General & Internal Medicine; Neurosciences & Neurology
GA DP2QY
UT WOS:000378336200269
ER
PT J
AU Cota, M
Moses, A
Diaz-Arrastia, R
Latour, L
Turtzo, LC
AF Cota, Martin
Moses, Anita
Diaz-Arrastia, Ramon
Latour, Lawrence
Turtzo, L. Christine
TI DISCORDANCE BETWEEN DOCUMENTED CRITERIA AND WRITTEN DIAGNOSIS OF TBI IN
A LEVEL 1 TRAUMA HOSPITAL EMERGENCY DEPARTMENT
SO JOURNAL OF NEUROTRAUMA
LA English
DT Meeting Abstract
CT 34th Annual National Neurotrauma Symposium
CY JUN 26-29, 2016
CL Lexington, KY
DE chart review; diagnosis
C1 [Cota, Martin; Moses, Anita] NINDS, CNRM, NIH, Stroke Branch, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
[Cota, Martin; Moses, Anita; Latour, Lawrence; Turtzo, L. Christine] NINDS, NIH, Stroke Branch, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
[Diaz-Arrastia, Ramon] CNRM, Rockville, MD USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 0897-7151
EI 1557-9042
J9 J NEUROTRAUM
JI J. Neurotrauma
PD JUL 1
PY 2016
VL 33
IS 13
MA PSB-227
BP A94
EP A94
PG 1
WC Critical Care Medicine; Clinical Neurology; Neurosciences
SC General & Internal Medicine; Neurosciences & Neurology
GA DP2QY
UT WOS:000378336200256
ER
PT J
AU Griffin, A
Tolpygo, A
Parikh, G
Turtzo, C
Moses, A
Ray-Chaudhury, A
Dardzinksi, B
Mitra, P
Latour, L
AF Griffin, Allison
Tolpygo, Alexander
Parikh, Gunjan
Turtzo, Christine
Moses, Anita
Ray-Chaudhury, Abhik
Dardzinksi, Bernard
Mitra, Partha
Latour, Lawrence
TI MRI EVALUATION OF MICROBLEEDS MAY REVEAL ONLY THE TIP OF THE ICEBERG: A
3D HISTOLOGICAL ANALYSIS
SO JOURNAL OF NEUROTRAUMA
LA English
DT Meeting Abstract
CT 34th Annual National Neurotrauma Symposium
CY JUN 26-29, 2016
CL Lexington, KY
C1 [Griffin, Allison; Turtzo, Christine; Moses, Anita; Ray-Chaudhury, Abhik; Latour, Lawrence] NINDS, CNRM, HJF, NIH,SB, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
[Tolpygo, Alexander; Mitra, Partha] Cold Spring Harbor Lab, POB 100, Cold Spring Harbor, NY 11724 USA.
[Parikh, Gunjan] Univ Maryland, Shock Trauma, Baltimore, MD 21201 USA.
[Dardzinksi, Bernard] Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 0897-7151
EI 1557-9042
J9 J NEUROTRAUM
JI J. Neurotrauma
PD JUL 1
PY 2016
VL 33
IS 13
MA PSA-132
BP A59
EP A59
PG 1
WC Critical Care Medicine; Clinical Neurology; Neurosciences
SC General & Internal Medicine; Neurosciences & Neurology
GA DP2QY
UT WOS:000378336200160
ER
PT J
AU Haber, M
Hutchinson, E
Irfanoglu, O
Cheng, T
Namjoshi, D
Cripton, P
Sadeghi, N
Wellington, C
Diaz-Arrastia, R
Pierpaoli, C
AF Haber, Margalit
Hutchinson, Elizabeth
Irfanoglu, Okan
Cheng, Tom
Namjoshi, Dhananjay
Cripton, Peter
Sadeghi, Neda
Wellington, Cheryl
Diaz-Arrastia, Ramon
Pierpaoli, Carlo
TI DTI ABNORMALITIES IN THE CLOSED HEAD INJURY MODEL OF ENGINEERED
ROTATIONAL ACCELERATION (CHIMERA) MOUSE MODEL
SO JOURNAL OF NEUROTRAUMA
LA English
DT Meeting Abstract
CT 34th Annual National Neurotrauma Symposium
CY JUN 26-29, 2016
CL Lexington, KY
DE DTI; animal model; CHIMERA; diffuse axonal injury; diffusion MRI
C1 [Haber, Margalit] Henry M Jackson Fdn Adv Mil Med, CNRM, Rockville, MD USA.
[Haber, Margalit; Hutchinson, Elizabeth; Irfanoglu, Okan; Sadeghi, Neda; Pierpaoli, Carlo] NICHD, NIH, SQITS, Bethesda, MD USA.
[Cheng, Tom; Namjoshi, Dhananjay; Wellington, Cheryl] Univ British Columbia, Pathol & Lab Med, Vancouver, BC V5Z 1M9, Canada.
[Cripton, Peter] Univ British Columbia, Biomech Engn, Vancouver, BC V5Z 1M9, Canada.
[Haber, Margalit; Diaz-Arrastia, Ramon] USUHS, Neurol, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 2
U2 2
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 0897-7151
EI 1557-9042
J9 J NEUROTRAUM
JI J. Neurotrauma
PD JUL 1
PY 2016
VL 33
IS 13
MA PSB-270
BP A109
EP A110
PG 2
WC Critical Care Medicine; Clinical Neurology; Neurosciences
SC General & Internal Medicine; Neurosciences & Neurology
GA DP2QY
UT WOS:000378336200299
ER
PT J
AU Kenney, K
Amyot, F
Turtzo, LC
Haber, M
Silverman, E
Moore, C
Shenouda, C
Wasserman, E
Diaz-Arrastia, R
AF Kenney, Kimbra
Amyot, Franck
Turtzo, L. Christine
Haber, Margalit
Silverman, Erika
Moore, Carol
Shenouda, Christian
Wasserman, Eric
Diaz-Arrastia, Ramon
TI CEREBROVASCULAR REACTIVITY IN CHRONIC TRAUMATIC BRAIN INJURY-THE
SILDENAFIL EFFECT
SO JOURNAL OF NEUROTRAUMA
LA English
DT Meeting Abstract
CT 34th Annual National Neurotrauma Symposium
CY JUN 26-29, 2016
CL Lexington, KY
DE cerebrovascular reactivity; traumatic vascular injury; biomarker;
phosphodiesterase 5 (PDE5) inhibitor; sildenafil
C1 [Kenney, Kimbra; Amyot, Franck; Haber, Margalit; Silverman, Erika; Moore, Carol; Diaz-Arrastia, Ramon] USUHS, Neurol, Bethesda, MD USA.
[Turtzo, L. Christine; Wasserman, Eric] NINDS, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
[Shenouda, Christian] NIH, Phys Med & Rehabil, Bldg 10, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 0897-7151
EI 1557-9042
J9 J NEUROTRAUM
JI J. Neurotrauma
PD JUL 1
PY 2016
VL 33
IS 13
MA PSA-022
BP A21
EP A21
PG 1
WC Critical Care Medicine; Clinical Neurology; Neurosciences
SC General & Internal Medicine; Neurosciences & Neurology
GA DP2QY
UT WOS:000378336200052
ER
PT J
AU Merchant-Borna, K
Olivera, A
Gill, J
Bazarian, J
AF Merchant-Borna, Kian
Olivera, Anlys
Gill, Jessica
Bazarian, Jeffrey
TI LONGITUDINAL TAU CONCENTRATIONS IN SWEAT FOLLOWING SPORT-RELATED
CONCUSSION: A PILOT STUDY
SO JOURNAL OF NEUROTRAUMA
LA English
DT Meeting Abstract
CT 34th Annual National Neurotrauma Symposium
CY JUN 26-29, 2016
CL Lexington, KY
DE tau; sports; sport related concussion; sweat
C1 [Merchant-Borna, Kian; Bazarian, Jeffrey] Univ Rochester, Med Ctr, Emergency Med, Rochester, NY 14627 USA.
[Olivera, Anlys; Gill, Jessica] NINR, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 0897-7151
EI 1557-9042
J9 J NEUROTRAUM
JI J. Neurotrauma
PD JUL 1
PY 2016
VL 33
IS 13
MA PSB-248
BP A101
EP A102
PG 2
WC Critical Care Medicine; Clinical Neurology; Neurosciences
SC General & Internal Medicine; Neurosciences & Neurology
GA DP2QY
UT WOS:000378336200277
ER
PT J
AU Parikh, G
Griffin, A
Moses, A
Edwards, N
Cota, M
Nair, G
Turtzo, C
Reich, D
Armstrong, R
Ray-Chaudury, A
Perl, D
Latour, L
AF Parikh, Gunjan
Griffin, Allison
Moses, Anita
Edwards, Nancy
Cota, Martin
Nair, Govind
Turtzo, Christine
Reich, Daniel
Armstrong, Regina
Ray-Chaudury, Abhik
Perl, Daniel
Latour, Lawrence
TI A WINDOW INTO THE WHITE MATTER RESPONSE TO PRIMARY MICROVASCULAR
INJURY-2D HISTOLOGICAL ANALYSIS OF ACUTE TRAUMATIC MICROBLEEDS
SO JOURNAL OF NEUROTRAUMA
LA English
DT Meeting Abstract
CT 34th Annual National Neurotrauma Symposium
CY JUN 26-29, 2016
CL Lexington, KY
DE histology; MRI; microvascular; extracellular matrix; ischemia; human
C1 [Parikh, Gunjan] Univ Maryland, Sch Med, R Adams Cowley Shock Trauma Ctr, Neurocrit Care, Baltimore, MD 21201 USA.
[Parikh, Gunjan; Edwards, Nancy; Nair, Govind; Reich, Daniel; Ray-Chaudury, Abhik; Latour, Lawrence] NINDS, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
[Griffin, Allison; Moses, Anita; Cota, Martin; Turtzo, Christine; Armstrong, Regina; Perl, Daniel; Latour, Lawrence] CNRM, Bethesda, MD USA.
[Armstrong, Regina; Perl, Daniel] USUHS, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 0897-7151
EI 1557-9042
J9 J NEUROTRAUM
JI J. Neurotrauma
PD JUL 1
PY 2016
VL 33
IS 13
MA PSA-134
BP A60
EP A60
PG 1
WC Critical Care Medicine; Clinical Neurology; Neurosciences
SC General & Internal Medicine; Neurosciences & Neurology
GA DP2QY
UT WOS:000378336200162
ER
PT J
AU Qu, BX
Bogoslovsky, T
Cota, M
Latour, L
Diaz-Arrastia, R
AF Qu, Baoxi
Bogoslovsky, Tanya
Cota, Martin
Latour, Lawrence
Diaz-Arrastia, Ramon
TI PHOSPHORYLATED NEUROFILAMENT HEAVY CHAIN (PNF-H), VON WILLEBRAND FACTOR
(VWF), AND CELLULAR FIBRONECTIN (CFN) IN PLASMA AFTER MTBI
SO JOURNAL OF NEUROTRAUMA
LA English
DT Meeting Abstract
CT 34th Annual National Neurotrauma Symposium
CY JUN 26-29, 2016
CL Lexington, KY
DE Von Willebrand factor; cellular fibronectin; phosphorylated
neurofilament H; mild TBI
C1 [Qu, Baoxi; Bogoslovsky, Tanya; Diaz-Arrastia, Ramon] Uniformed Serv Univ Hlth Sci, Neurol, Bethesda, MD 20814 USA.
[Bogoslovsky, Tanya; Cota, Martin; Latour, Lawrence; Diaz-Arrastia, Ramon] NINDS, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
[Qu, Baoxi; Bogoslovsky, Tanya; Cota, Martin; Latour, Lawrence; Diaz-Arrastia, Ramon] Ctr Neurosci & Regenerat Med, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 0897-7151
EI 1557-9042
J9 J NEUROTRAUM
JI J. Neurotrauma
PD JUL 1
PY 2016
VL 33
IS 13
MA PSA-019
BP A19
EP A20
PG 2
WC Critical Care Medicine; Clinical Neurology; Neurosciences
SC General & Internal Medicine; Neurosciences & Neurology
GA DP2QY
UT WOS:000378336200049
ER
PT J
AU Tolpygo, A
Lodato, Z
Ferrante, D
Chaudhury, AR
Dardinski, B
Griffin, A
Moses, A
Nair, G
Parikh, G
Perl, DP
Mitra, PP
Latour, L
AF Tolpygo, Alexander
Lodato, Z.
Ferrante, D.
Chaudhury, A. R.
Dardinski, B.
Griffin, A.
Moses, A.
Nair, G.
Parikh, G.
Perl, D. P.
Mitra, P. P.
Latour, L.
TI ADVANCES TOWARD 3D HISTOLOGICAL RECONSTRUCTION OF TRAUMATIC VASCULAR
INJURY
SO JOURNAL OF NEUROTRAUMA
LA English
DT Meeting Abstract
CT 34th Annual National Neurotrauma Symposium
CY JUN 26-29, 2016
CL Lexington, KY
DE histology; digital; pathology; whole-slide imaging; TBI
C1 [Tolpygo, Alexander; Lodato, Z.; Ferrante, D.; Mitra, P. P.] CSHL, Cold Spring Harbor, NY USA.
[Griffin, A.; Moses, A.; Perl, D. P.; Latour, L.] CNRM, Bethesda, MD USA.
[Dardinski, B.; Perl, D. P.] USUHS, Bethesda, MD USA.
[Chaudhury, A. R.; Nair, G.; Parikh, G.; Latour, L.] NINDS, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
[Parikh, G.] Univ Maryland, College Pk, MD 20742 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 0897-7151
EI 1557-9042
J9 J NEUROTRAUM
JI J. Neurotrauma
PD JUL 1
PY 2016
VL 33
IS 13
MA PSB-308
BP A123
EP A123
PG 1
WC Critical Care Medicine; Clinical Neurology; Neurosciences
SC General & Internal Medicine; Neurosciences & Neurology
GA DP2QY
UT WOS:000378336200337
ER
PT J
AU Tu, TW
Papadakis, G
Ibrahim, W
Jikaria, N
Reid, W
Hammoud, D
Frank, J
AF Tu, Tsang-Wei
Papadakis, Georgios
Ibrahim, Wael
Jikaria, Neekita
Reid, William
Hammoud, Dima
Frank, Joseph
TI SENSITIVITY COMPARISON BETWEEN GLUCOCEST, FDG-PET AND
2DG-AUTORADIOGRAPHY IN MEASURING GLUCOSE METABOLIC DISORDER IN MILD TBI
SO JOURNAL OF NEUROTRAUMA
LA English
DT Meeting Abstract
CT 34th Annual National Neurotrauma Symposium
CY JUN 26-29, 2016
CL Lexington, KY
DE glucoCEST; FDG-PET; 2DG Autoradiography; diffuse axonal injury;
diffusion tensor imaging
C1 [Tu, Tsang-Wei; Papadakis, Georgios; Ibrahim, Wael; Jikaria, Neekita; Reid, William; Hammoud, Dima; Frank, Joseph] NIH, Radiol & Imaging Sci, Bldg 10, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 2
U2 2
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 0897-7151
EI 1557-9042
J9 J NEUROTRAUM
JI J. Neurotrauma
PD JUL 1
PY 2016
VL 33
IS 13
MA PSB-272
BP A110
EP A110
PG 1
WC Critical Care Medicine; Clinical Neurology; Neurosciences
SC General & Internal Medicine; Neurosciences & Neurology
GA DP2QY
UT WOS:000378336200301
ER
PT J
AU Turtzo, L
Parikh, G
MacLaren, J
Williford, J
Moses, A
Cota, M
Latour, L
AF Turtzo, L.
Parikh, Gunjan
MacLaren, Judy
Williford, Josh
Moses, Anita
Cota, Martin
Latour, Larry
TI ISCHEMIA AND LATE BLOOD BRAIN BARRIER DISRUPTION DURING EVOLUTION OF
WHITE MATTER MICROVASCULAR INJURY
SO JOURNAL OF NEUROTRAUMA
LA English
DT Meeting Abstract
CT 34th Annual National Neurotrauma Symposium
CY JUN 26-29, 2016
CL Lexington, KY
DE traumatic microvascular injury
C1 [Turtzo, L.; Latour, Larry] NINDS, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
[Parikh, Gunjan] UMD, Shock Trauma, Baltimore, MD USA.
[MacLaren, Judy; Williford, Josh] Suburban Hosp, Bethesda, MD USA.
[Moses, Anita; Cota, Martin; Latour, Larry] CNRM, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 0897-7151
EI 1557-9042
J9 J NEUROTRAUM
JI J. Neurotrauma
PD JUL 1
PY 2016
VL 33
IS 13
MA PSB-273
BP A110
EP A111
PG 2
WC Critical Care Medicine; Clinical Neurology; Neurosciences
SC General & Internal Medicine; Neurosciences & Neurology
GA DP2QY
UT WOS:000378336200302
ER
PT J
AU D'Angio, CT
Ambalavanan, N
Carlo, WA
McDonald, SA
Skogstrand, K
Hougaard, DM
Shankaran, S
Goldberg, RN
Ehrenkranz, RA
Tyson, JE
Stoll, BJ
Das, A
Higgins, RD
AF D'Angio, Carl T.
Ambalavanan, Namasivayam
Carlo, Waldemar A.
McDonald, Scott A.
Skogstrand, Kristin
Hougaard, David M.
Shankaran, Seetha
Goldberg, Ronald N.
Ehrenkranz, Richard A.
Tyson, Jon E.
Stoll, Barbara J.
Das, Abhik
Higgins, Rosemary D.
CA Eunice Kennedy Shriver Natl Inst C
TI Blood Cytokine Profiles Associated with Distinct Patterns of
Bronchopulmonary Dysplasia among Extremely Low Birth Weight Infants
SO JOURNAL OF PEDIATRICS
LA English
DT Article
ID CHRONIC LUNG-DISEASE; PREMATURE-INFANTS; PRETERM INFANTS; INFLAMMATORY
MARKERS; PULMONARY; INTERLEUKIN-8; FLUID; EXPRESSION; HYPEROXIA;
ASPIRATE
AB Objective To explore differences in blood cytokine profiles among distinct bronchopulmonary dysplasia (BPD) patterns.
Study design We evaluated blood spots collected from 943 infants born at <= 1000 g and surviving to 28 days on postnatal days 1, 3, 7, 14, and 21 for 25 cytokines. Infants were assigned to the following lung disease patterns: (1) no lung disease (NLD); (2) respiratory distress syndrome without BPD; (3) classic BPD (persistent exposure to supplemental oxygen until 28 days of age); or (4) atypical BPD (period without supplemental oxygen before 28 days). Median cytokine levels for infants with BPD were compared with the IQR of results among infants with NLD.
Results The distribution of enrolled infants by group was as follows: 69 (NLD), 73 (respiratory distress syndrome), 381 (classic BPD), and 160 (atypical BPD). The remaining 260 infants could not be classified because of missing data (104) or not fitting a predefined pattern (156). Median levels of 3 cytokines (elevated interleukin [IL]-8, matrix metalloproteinase-9; decreased granulocyte macrophage colony-stimulating factor) fell outside the IQR for at least 2 time points in both infants with atypical and classic BPD. Profiles of 7 cytokines (IL-6, IL-10, IL-18, macrophage inflammatory protein-1a, C-reactive protein, brain-derived neurotrophic factor, regulated on activation, normal T cell expressed and secreted) differed between infants with classic and atypical BPD.
Conclusions Blood cytokine profiles may differ between infants developing classic and atypical BPD. These dissimilarities suggest the possibility that differing mechanisms could explain the varied patterns of pathophysiology of lung disease in extremely premature infants.
C1 [D'Angio, Carl T.] Univ Rochester, Sch Med & Dent, Strong Childrens Res Ctr, Rochester, NY 14642 USA.
[Ambalavanan, Namasivayam; Carlo, Waldemar A.] Univ Alabama Birmingham, Dept Pediat, Birmingham, AL USA.
[McDonald, Scott A.] RTI Int, Stat & Epidemiol Unit, Res Triangle Pk, NC USA.
[Skogstrand, Kristin; Hougaard, David M.] Statens Serum Inst, Dept Clin Biochem Immunol & Genet, Danish Ctr Neonatal Screening, DK-2300 Copenhagen, Denmark.
[Shankaran, Seetha] Wayne State Univ, Dept Pediat, Detroit, MI 48202 USA.
[Goldberg, Ronald N.] Duke Univ, Dept Pediat, Durham, NC 27706 USA.
[Ehrenkranz, Richard A.] Yale Univ, Sch Med, Dept Pediat, New Haven, CT 06510 USA.
[Tyson, Jon E.] Univ Texas Houston, Sch Med, Dept Pediat, Houston, TX USA.
[Stoll, Barbara J.] Emory Univ, Sch Med, Dept Pediat, Childrens Healthcare Atlanta, Atlanta, GA USA.
[Das, Abhik] RTI Int, Stat & Epidemiol Unit, Rockville, MD USA.
[Higgins, Rosemary D.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
RP D'Angio, CT (reprint author), Univ Rochester, Sch Med & Dent, Neonatol, Box 651,601 Elmwood Ave, Rochester, NY 14642 USA.
EM carl_dangio@urmc.rochester.edu
OI Ambalavanan, Namasivayam/0000-0003-0731-9092
FU National Institutes of Health (NIH) [M01 RR30, M01 RR32, M01 RR39, M01
RR70, M01 RR80, M01 RR633, M01 RR750, M01 RR997, M01 RR6022, M01 RR7122,
M01 RR8084, M01 RR16587]; NICHD [U01 HD36790, U10 HD21364, U10 HD21373,
U10 HD21385, U10 HD21397, U10 HD21415, U10 HD27851, U10 HD27853, U10
HD27856, U10 HD27871, U10 HD27880, U10 HD27881, U10 HD27904, U10
HD34216, U10 HD40461, U10 HD40492, U10 HD40498, U10 HD40689, 1 U10 HD
068263]; Centers for Disease Control and Prevention (CDC) [Y1-HD-500001]
FX The Neonatal Research Network's Cytokines Study was supported by the
National Institutes of Health (NIH; M01 RR30, M01 RR32, M01 RR39, M01
RR70, M01 RR80, M01 RR633, M01 RR750, M01 RR997, M01 RR6022, M01 RR7122,
M01 RR8084, M01 RR16587), the NICHD (U01 HD36790, U10 HD21364, U10
HD21373, U10 HD21385, U10 HD21397, U10 HD21415, U10 HD27851, U10
HD27853, U10 HD27856, U10 HD27871, U10 HD27880, U10 HD27881, U10
HD27904, U10 HD34216, U10 HD40461, U10 HD40492, U10 HD40498, U10
HD40689), and the Centers for Disease Control and Prevention (CDC;
Interagency Agreement Y1-HD-500001). C.D. is supported by NICHD (1 U10
HD 068263). Participating sites collected data and transmitted it to RTI
International, the data coordinating center for the network, which
stored, managed, and analyzed the data for this study. Although NICHD
and CDC staff did have input into the study design, conduct, analysis,
and manuscript drafting, the content is solely the responsibility of the
authors and does not necessarily represent the official views of NICHD
or CDC. The authors declare no conflicts of interest.
NR 27
TC 2
Z9 2
U1 1
U2 5
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0022-3476
EI 1097-6833
J9 J PEDIATR-US
JI J. Pediatr.
PD JUL
PY 2016
VL 174
BP 45
EP 51
DI 10.1016/j.jpeds.2016.03.058
PG 7
WC Pediatrics
SC Pediatrics
GA DP6PX
UT WOS:000378620800011
PM 27117196
ER
PT J
AU Rice, CE
Zablotsky, B
Avila, RM
Colpe, LJ
Schieve, LA
Pringle, B
Blumberg, SJ
AF Rice, Catherine E.
Zablotsky, Benjamin
Avila, Rosa M.
Colpe, Lisa J.
Schieve, Laura A.
Pringle, Beverly
Blumberg, Stephen J.
TI Reported Wandering Behavior among Children with Autism Spectrum Disorder
and/or Intellectual Disability
SO JOURNAL OF PEDIATRICS
LA English
DT Article
ID CHALLENGING BEHAVIORS; FUNCTIONAL-ANALYSIS; CARE NEEDS; ELOPEMENT;
ADULTS; HEALTH; DEATH
AB Objective To characterize wandering, or elopement, among children with autism spectrum disorder (ASD) and intellectual disability.
Study design Questions on wandering in the previous year were asked of parents of children with ASD with and without intellectual disability and children with intellectual disability without ASD as part of the 2011 Survey of Pathways to Diagnosis and Services. The Pathways study sample was drawn from the much larger National Survey of Children with Special Health Care Needs conducted in 2009-2010.
Results For children with special healthcare needs diagnosed with either ASD, intellectual disability, or both, wandering or becoming lost during the previous year was reported for more than 1 in 4 children. Wandering was highest among children with ASD with intellectual disability (37.7%) followed by children with ASD without intellectual disability (32.7%), and then children with intellectual disability without ASD (23.7%), though the differences between these groups were not statistically significant.
Conclusions This study affirms that wandering among children with ASD, regardless of intellectual disability status, is relatively common. However, wandering or becoming lost in the past year was also reported for many children with intellectual disability, indicating the need to broaden our understanding of this safety issue to other developmental disabilities.
C1 [Rice, Catherine E.; Schieve, Laura A.] Ctr Dis Control & Prevent, Natl Ctr Birth Defects & Dev Disabil, Baltimore, MD USA.
[Rice, Catherine E.] Emory Univ, Sch Med, Dept Psychiat & Behav Sci, Atlanta, GA 30322 USA.
[Zablotsky, Benjamin; Blumberg, Stephen J.] Ctr Dis Control & Prevent, Natl Ctr Hlth Stat, Hyattsville, MD 20782 USA.
[Avila, Rosa M.] Univ Washington, Sch Publ Hlth, Seattle, WA 98195 USA.
[Colpe, Lisa J.; Pringle, Beverly] NIMH, NIH, Bethesda, MD 20892 USA.
RP Rice, CE (reprint author), Emory Univ, Sch Med, Dept Psychiat & Behav Sci, Atlanta, GA 30322 USA.
EM cerice@emory.edu
FU National Institute of Mental Health; American Recovery and Reinvestment
Act (ARRA) [111-5]
FX Funded by the National Institute of Mental Health with funds available
from the American Recovery and Reinvestment Act of 2009 (ARRA) (Public
Law 111-5). The findings and conclusions in this report are those of the
authors and do not necessarily represent the official position of the
Centers for Disease and Control and Prevention, Emory University, the
University of Washington, or the National Institute of Mental Health.
The authors declare no conflicts of interest.
NR 28
TC 0
Z9 0
U1 2
U2 2
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0022-3476
EI 1097-6833
J9 J PEDIATR-US
JI J. Pediatr.
PD JUL
PY 2016
VL 174
BP 232
EP 239
DI 10.1016/j.jpeds.2016.03.047
PG 8
WC Pediatrics
SC Pediatrics
GA DP6PX
UT WOS:000378620800044
PM 27157446
ER
PT J
AU Bansal, N
Carpenter, MA
Weiner, DE
Levey, AS
Pfeffer, M
Kusek, JW
Cai, JW
Hunsicker, LG
Park, M
Bennett, M
Liu, KD
Hsu, CY
AF Bansal, Nisha
Carpenter, Myra A.
Weiner, Daniel E.
Levey, Andrew S.
Pfeffer, Marc
Kusek, John W.
Cai, Jianwen
Hunsicker, Lawrence G.
Park, Meyeon
Bennett, Michael
Liu, Kathleen D.
Hsu, Chi-yuan
TI Urine Injury Biomarkers and Risk of Adverse Outcomes in Recipients of
Prevalent Kidney Transplants: The Folic Acid for Vascular Outcome
Reduction in Transplantation Trial
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Article
ID GELATINASE-ASSOCIATED LIPOCALIN; TYPE-1 DIABETIC-PATIENTS;
GLOMERULAR-FILTRATION-RATE; DELAYED GRAFT FUNCTION; BINDING PROTEIN
GENE; STAGE RENAL-DISEASE; FATTY-ACID; CARDIOVASCULAR-DISEASE;
CARDIAC-SURGERY; PREDICTIVE BIOMARKERS
AB Recipients of kidney transplants (KTR) are at increased risk for cardiovascular events, graft failure, and death. It is unknown whether urine kidney injury biomarkers are associated with poor outcomes among KTRs. We conducted a post hoc analysis of the Folic Acid for Vascular Outcome Reduction in Transplantation (FAVORIT) Trial using a case-cohort study design, selecting participants with adjudicated cardiovascular events, graft failure, or death. Urine neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), IL-18, and liver-type fatty acid binding protein (L-FABP) were measured in spot urine samples and standardized to urine creatinine concentration. We adjusted for demographics, cardiovascular risk factors, eGFR, and urine albumin-to-creatinine ratio. Patients had 291 cardiovascular events, 257 graft failure events, and 359 deaths. Each log increase in urine NGAL/creatinine independently associated with a 24% greater risk of cardiovascular events (adjusted hazard ratio [aHR], 1.24; 95% confidence interval [95% CI], 1.06 to 1.45), a 40% greater risk of graft failure (aHR, 1.40; 95% CI, 1.16 to 1.68), and a 44% greater risk of death (aHR, 1.44; 95% Cl, 1.26 to 1.65). Urine KIM-1/creatinine and IL-18/creatinine independently associated with greater risk of death (aHR, 1.29; 95% CI, 1.03 to 1.61 and aHR, 1.25; 95% CI, 1.04 to 1.49 per log increase, respectively) but not with risk of cardiovascular events or graft failure. Urine L-FABP did not associate with any study outcomes. In conclusion, among prevalent KTRs, higher urine NGAL, KIM-1, and IL-18 levels independently and differentially associated with greater risk of adverse outcomes.
C1 [Bansal, Nisha] Univ Washington, Kidney Res Inst, Div Nephrol, Seattle, WA 98104 USA.
[Carpenter, Myra A.; Cai, Jianwen] Univ N Carolina, Dept Biostat, Chapel Hill, NC USA.
[Weiner, Daniel E.; Levey, Andrew S.] Tufts Med Ctr, Div Nephrol, Boston, MA USA.
[Pfeffer, Marc] Brigham & Womens Hosp, Div Cardiol, Boston, MA 02115 USA.
[Kusek, John W.] NIDDK, NIH, Bethesda, MD 20892 USA.
[Hunsicker, Lawrence G.] Univ Iowa, Coll Med, Dept Med, Iowa City, IA 52242 USA.
[Park, Meyeon; Liu, Kathleen D.; Hsu, Chi-yuan] Univ Calif San Francisco, Div Nephrol, San Francisco, CA 94143 USA.
[Bennett, Michael] Cincinnati Childrens Hosp, Dept Pediat, Cincinnati, OH USA.
RP Bansal, N (reprint author), Univ Washington, Kidney Res Inst, 908 Jefferson St,3rd Floor, Seattle, WA 98104 USA.
EM nbansal@nephrology.washington.edu
FU National Institutes of Health (NIH)/National Institute of Diabetes and
Digestive and Kidney Diseases (NIDDK) [K23 DK088865, K24 DK92291]; CKD
Biomarker Consortium [U01DK85649]; NIDDK [U01 DK61700-01]; Office of
Dietary Supplements, Department of Health and Human Services, the NIH
FX This work was supported by Grants K23 DK088865 (to N.B.) and K24 DK92291
(to C.-y.H.) from the National Institutes of Health (NIH)/National
Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). K.D.L.
and C.-y.H. are also supported by Grant U01DK85649 as members of the CKD
Biomarker Consortium. The Folic Acid for Vascular Outcome Reduction in
Transplantation Study was supported by Cooperative Agreement U01
DK61700-01 from the NIDDK, and additional financial support was from the
Office of Dietary Supplements, Department of Health and Human Services,
the NIH. Vitamins were provided by Pamlab, LLC.
NR 61
TC 3
Z9 3
U1 1
U2 3
PU AMER SOC NEPHROLOGY
PI WASHINGTON
PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA
SN 1046-6673
EI 1533-3450
J9 J AM SOC NEPHROL
JI J. Am. Soc. Nephrol.
PD JUL
PY 2016
VL 27
IS 7
BP 2109
EP 2121
DI 10.1681/ASN.2015030292
PG 13
WC Urology & Nephrology
SC Urology & Nephrology
GA DP9OD
UT WOS:000378824800025
PM 26538631
ER
PT J
AU Brown, P
Juarez, B
AF Brown, Patricia
Juarez, Bernadette
TI A word from USDA and OLAW
SO LAB ANIMAL
LA English
DT Editorial Material
C1 [Brown, Patricia] NIH, OLAW, OER, OD,NIH, Bldg 10, Bethesda, MD 20892 USA.
[Juarez, Bernadette] APHIS, USDA, AC, Riverdale Pk, MD USA.
RP Brown, P (reprint author), NIH, OLAW, OER, OD,NIH, Bldg 10, Bethesda, MD 20892 USA.
NR 3
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0093-7355
EI 1548-4475
J9 LAB ANIMAL
JI Lab Anim.
PD JUL
PY 2016
VL 45
IS 7
BP 250
EP 250
DI 10.1038/laban.1058
PG 1
WC Veterinary Sciences
SC Veterinary Sciences
GA DP8OQ
UT WOS:000378757900014
PM 27327010
ER
PT J
AU Nou, E
Lo, J
Hadigan, C
Grinspoon, SK
AF Nou, Eric
Lo, Janet
Hadigan, Colleen
Grinspoon, Steven K.
TI Pathophysiology and management of cardiovascular disease in patients
with HIV
SO LANCET DIABETES & ENDOCRINOLOGY
LA English
DT Review
ID HUMAN-IMMUNODEFICIENCY-VIRUS; ACUTE MYOCARDIAL-INFARCTION;
CORONARY-HEART-DISEASE; T-CELL-ACTIVATION; INTIMA-MEDIA THICKNESS;
C-REACTIVE PROTEIN; EPICARDIAL ADIPOSE-TISSUE; RANDOMIZED
CLINICAL-TRIAL; PLACEBO-CONTROLLED TRIAL; MULTICENTER AIDS COHORT
AB Results from several studies have suggested that people with HIV have an increased risk of cardiovascular disease, especially coronary heart disease, compared with people not infected with HIV. People living with HIV have an increased prevalence of traditional cardiovascular disease risk factors, and HIV-specific mechanisms such as immune activation. Although older, more metabolically harmful antiretroviral regimens probably contributed to the risk of cardiovascular disease, new data suggest that early and continuous use of modern regimens, which might have fewer metabolic effects, minimises the risk of myocardial infarction by maintaining viral suppression and decreasing immune activation. Even with antiretroviral therapy, however, immune activation persists in people with HIV and could contribute to accelerated atherosclerosis, especially of coronary lesions that are susceptible to rupture. Therefore, treatments that safely reduce inflammation in people with HIV could provide additional cardiovascular protection alongside treatment of both traditional and non-traditional risk factors.
C1 [Nou, Eric; Lo, Janet; Grinspoon, Steven K.] Massachusetts Gen Hosp, Program Nutr Metab, Boston, MA 02114 USA.
[Hadigan, Colleen] NIAID, NIH, Bethesda, MD USA.
RP Grinspoon, SK (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA.
EM sgrinspoon@mgh.harvard.edu
FU US National Institute of Allergies and Infectious Diseases Intramural
Program
FX This work was partly supported by the US National Institute of Allergies
and Infectious Diseases Intramural Program.
NR 137
TC 5
Z9 5
U1 3
U2 7
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 2213-8587
J9 LANCET DIABETES ENDO
JI Lancet Diabetes Endocrinol.
PD JUL
PY 2016
VL 4
IS 7
BP 598
EP 610
DI 10.1016/S2213-8587(15)00388-5
PG 13
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA DQ0CD
UT WOS:000378864700022
PM 26873066
ER
PT J
AU Wiestner, A
AF Wiestner, Adrian
TI Choosing frontline chemoimmunotherapy for CLL
SO LANCET ONCOLOGY
LA English
DT Editorial Material
ID CHRONIC LYMPHOCYTIC-LEUKEMIA; CYCLOPHOSPHAMIDE; FLUDARABINE; IBRUTINIB;
THERAPY; TRIAL
C1 [Wiestner, Adrian] NHLBI, NIH, Bldg 10, Bethesda, MD 20892 USA.
RP Wiestner, A (reprint author), NHLBI, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM wiestnera@mail.nih.gov
NR 10
TC 0
Z9 0
U1 6
U2 6
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1470-2045
EI 1474-5488
J9 LANCET ONCOL
JI Lancet Oncol.
PD JUL
PY 2016
VL 17
IS 7
BP 852
EP 854
DI 10.1016/S1470-2045(16)30118-8
PG 4
WC Oncology
SC Oncology
GA DQ1FO
UT WOS:000378947100035
PM 27216275
ER
PT J
AU Straub, H
Simon, C
Plunkett, BA
Endres, L
Adam, EK
Mckinney, C
Hobel, CJ
Thorp, JM
Raju, T
Shalowitz, M
AF Straub, Heather
Simon, Clarissa
Plunkett, Beth A.
Endres, Loraine
Adam, Emma K.
Mckinney, Chelsea
Hobel, Calvin J.
Thorp, John M.
Raju, Tonse
Shalowitz, Madeleine
TI Evidence for a Complex Relationship Among Weight Retention, Cortisol and
Breastfeeding in Postpartum Women
SO MATERNAL AND CHILD HEALTH JOURNAL
LA English
DT Article
DE Postpartum weight retention; Cortisol slope; Breast feeding; Stress
ID PITUITARY-ADRENAL AXIS; BODY-FAT DISTRIBUTION; SALIVARY CORTISOL;
OBESITY; SECRETION; RISK; MOTHERS; STRESS; ADULTS; GAIN
AB Objective To assess the relationship between cortisol slope, a biologic marker of stress, and postpartum weight retention. Methods We included 696 women in a secondary analysis from a multi-site study conducted using principles of community-based participatory research to study multi-level sources of stress on pregnancy outcomes. As a stress marker, we included salivary cortisol slope; the rate of cortisol decline across the day. Pre-pregnancy weight and demographic data were obtained from the medical records. At 6 months postpartum, patients were weighed and returned saliva samples. We built stepwise regression models to assess the effect of demographic variables, cortisol slope and cortisol covariates (wake time, tobacco use and breastfeeding) on postpartum weight retention. Results 45.5 % of participants were African American, 29.2 % White, and 25.3 % Hispanic. Of the Hispanic women 62.5 % were Spanish speaking and 37.5 % were English speaking. In general, participants were young, multiparous, and overweight. Postpartum, almost half (47.6 %) of women studied retained > 10 lbs. In multivariable analysis including age, pre-pregnancy BMI and public insurance, cortisol slope was significantly associated with weight retention (beta = -1.90, 95 % CI = 0.22-3.58). However, when the model was adjusted for the cortisol covariates, breastfeeding (beta = -0.63, 95 % CI = -1.01 to -0.24) and public insurance (beta = 0.62, 95 % CI = 0.20-1.04) were the two strongest correlates of weight retention. Conclusions for Practice The association between cortisol slope and postpartum weight retention appears to be influenced breastfeeding status.
C1 [Straub, Heather; Plunkett, Beth A.; Endres, Loraine] NorthShore Univ HealthSyst, Evanston Hosp, Dept Obstet & Gynecol, Evanston, IL 60201 USA.
[Straub, Heather] MultiCare Reg Maternal Fetal Med, MS 1105-2-MFM,1105 Div Ave,Suite 201, Tacoma, WA 98403 USA.
[Simon, Clarissa; Adam, Emma K.] Northwestern Univ, Inst Policy Res, Evanston, IL USA.
[Mckinney, Chelsea; Shalowitz, Madeleine] NorthShore Univ HealthSyst, Res Inst, Evanston, IL USA.
[Hobel, Calvin J.] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA USA.
[Thorp, John M.] Univ N Carolina, Dept Obstet & Gynecol, Chapel Hill, NC USA.
[Raju, Tonse] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA.
RP Straub, H (reprint author), NorthShore Univ HealthSyst, Evanston Hosp, Dept Obstet & Gynecol, Evanston, IL 60201 USA.; Straub, H (reprint author), MultiCare Reg Maternal Fetal Med, MS 1105-2-MFM,1105 Div Ave,Suite 201, Tacoma, WA 98403 USA.
EM HeatherStraubMD@gmail.com
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development [U HD44207, U HD44219, U HD44226, U HD44245, U HD44253, U
HD54791, U HD54019, U HD44226-05S1, U HD44245-06S1, R03 HD59584];
National Institute for Nursing Research [U NR008929]
FX The Community Child Health Network is supported through cooperative
agreements with the Eunice Kennedy Shriver National Institute of Child
Health and Human Development (U HD44207, U HD44219, U HD44226, U
HD44245, U HD44253, U HD54791, U HD54019, U HD44226-05S1, U
HD44245-06S1, R03 HD59584) and the National Institute for Nursing
Research (U NR008929).
NR 31
TC 0
Z9 0
U1 2
U2 7
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1092-7875
EI 1573-6628
J9 MATERN CHILD HLTH J
JI Matern. Child Health J.
PD JUL
PY 2016
VL 20
IS 7
BP 1375
EP 1383
DI 10.1007/s10995-016-1934-z
PG 9
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA DP8MK
UT WOS:000378752000008
PM 26968183
ER
PT J
AU Ochiai, E
Sa, QL
Perkins, S
Grigg, ME
Suzuki, Y
AF Ochiai, Eri
Sa, Qila
Perkins, Sara
Grigg, Michael E.
Suzuki, Yasuhiro
TI CD8(+) T cells remove cysts of Toxoplasma gondii from the brain mostly
by recognizing epitopes commonly expressed by or cross-reactive between
type II and type III strains of the parasite
SO MICROBES AND INFECTION
LA English
DT Article
DE Toxoplasma gondii; Cyst; Genotype; CD8(+) T cells; Perforin
ID CLINICAL FINDINGS; INTERFERON-GAMMA; INFECTION; GENOTYPE; RESISTANCE;
RESPONSES
AB Our previous study demonstrated that CD8(+) T cells remove cysts of Toxoplasma gondii from the brain through perforin-mediated mechanisms. We here show that a transfer of CD8(+) immune T cells primed with a type II or a type III strain of T. gondii both efficiently removed cysts of a type II strain from infected SCID mice, although the former tended to be slightly more efficient than the latter. Similarly, a transfer of type II-primed CD8(+) T cells removed cysts of a type III strain. Therefore, CD8(+) T cells are capable of removing T. gondii cysts by recognizing epitopes commonly expressed in types II and III strains or cross-reactive between these two genotypes. (C) 2016 Published by Elsevier Masson SAS on behalf of Institut Pasteur.
C1 [Ochiai, Eri; Sa, Qila; Perkins, Sara; Suzuki, Yasuhiro] Univ Kentucky, Coll Med, Dept Microbiol Immunol & Mol Genet, 800 Rose St, Lexington, KY 40536 USA.
[Grigg, Michael E.] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
[Ochiai, Eri] Tokyo Univ Agr & Technol, Dept Biotechnol & Life Sci, Tokyo, Japan.
RP Suzuki, Y (reprint author), Univ Kentucky, Coll Med, Dept Microbiol Immunol & Mol Genet, 800 Rose St, Lexington, KY 40536 USA.
EM yasu.suzuki@uky.edu
FU NIH [AI095032, AI073576, AI078756]; Intramural Research Program of the
National Institutes of Health, NIAID
FX The studies are supported in part by NIH grants (AI095032, AI073576, and
AI078756) (Y.S.). This work was also supported, in part, by the
Intramural Research Program of the National Institutes of Health, NIAID
(M.E.G.). M.E.G. is a Scholar of the Canadian Institute for Advanced
Research (CIFAR) Integrated Microbial Biodiversity program.
NR 21
TC 0
Z9 0
U1 4
U2 4
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1286-4579
EI 1769-714X
J9 MICROBES INFECT
JI Microbes Infect.
PD JUL-AUG
PY 2016
VL 18
IS 7-8
DI 10.1016/j.micinf.2016.03.013
PG 6
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA DP9WK
UT WOS:000378848400009
ER
PT J
AU Johnson, AR
Qin, YY
Cozzo, AJ
Freemerman, AJ
Huang, MJ
Zhao, LY
Sampey, BP
Milner, JJ
Beck, MA
Damania, B
Rashid, N
Galanko, JA
Lee, DP
Edin, ML
Zeldin, DC
Fueger, PT
Dietz, B
Stahl, A
Wu, Y
Mohlke, KL
Makowski, L
AF Johnson, Amy R.
Qin, Yuanyuan
Cozzo, Alyssa J.
Freemerman, Alex J.
Huang, Megan J.
Zhao, Liyang
Sampey, Brante P.
Milner, J. Justin
Beck, Melinda A.
Damania, Blossom
Rashid, Naim
Galanko, Joseph A.
Lee, Douglas P.
Edin, Matthew L.
Zeldin, Darryl C.
Fueger, Patrick T.
Dietz, Brittney
Stahl, Andreas
Wu, Ying
Mohlke, Karen L.
Makowski, Liza
TI Metabolic reprogramming through fatty acid transport protein 1 (FATP1)
regulates macrophage inflammatory potential and adipose inflammation
SO MOLECULAR METABOLISM
LA English
DT Article
DE Adipose tissue macrophage; M2 macrophage; Obesity; Glycolysis;
Crown-like structures; Mitochondria
ID TISSUE MACROPHAGES; INSULIN-RESISTANCE; BINDING PROTEINS;
GENE-EXPRESSION; PROINFLAMMATORY PHENOTYPE; RHEUMATOID-ARTHRITIS;
GLUCOSE-METABOLISM; DIABETES-MELLITUS; SKELETAL-MUSCLE; DENDRITIC CELL
AB Objective: A novel approach to regulate obesity-asociated adipose inflammation may be through metabolic reprogramming of macrophages (M Phi s). Broadly speaking, M Phi s dependent on glucose are pro-inflammatory, clasically activated M Phi s (CAM), which contribute to adipose inflammation and insulin resistance. In contrast, M Phi s that primarily metabolize fatty acids are alternatively activated M Phi s (AAM) and maintain tisue insulin sensitivity. In actuality, there is much flexibility and overlap in the CAM-AAM spectrum in vivo dependent upon various stimuli in the microenvironment. We hypothesized that specific lipid trafficking proteins, e.g. fatty acid transport protein 1 (FATP1), would direct M Phi s fatty acid transport and metabolism to limit inflammation and contribute to the maintenance of adipose tisue homeostasis.
Methods: Bone marrow derived M Phi s (BMDMs) from Fatp1(-/-) and Fatp1(+/+) mice were used to investigate FATP1-dependent substrate metabolism, bioenergetics, metabolomics, and inflammatory responses. We also generated C57BL/6J chimeric mice by bone marrow transplant specifically lacking hematopoetic FATP1 (Fatp1B(-/-)) and controls Fatp1B(+/+). Mice were challenged by high fat diet (HFD) or low fat diet (LFD) and analyses including MRI, glucose and insulin tolerance tests, flow cytometric, histologic, and protein quantification asays were conducted. Finally, an FATP1-overexpresing RAW 264.7 M Phi s cell line (FATP1-OE) and empty vector control (FATP1-EV) were developed as a gain of function model to test effects on substrate metabolism, bioenergetics, metabolomics, and inflammatory responses.
Results: Fatp1 is downregulated with pro-inflammatory stimulation of M Phi s. Fatp1(-/-) BMDMs and FATP1-OE RAW 264.7 M Phi s demonstrated that FATP1 reciprocally controled metabolic flexibility, i.e. lipid and glucose metabolism, which was asociated with inflammatory response. Supporting our previous work demonstrating the positive relationship between glucose metabolism and inflammation, los of FATP1 enhanced glucose metabolism and exaggerated the pro-inflammatory CAM phenotype. Fatp1B(-/-) chimeras fed a HFD gained more epididymal white adipose mas, which was inflamed and oxidatively stresed, compared to HFD-fed Fatp1B(+/+) controls. Adipose tisue macrophages displayed a CAM-like phenotype in the absence of Fatp1. Conversely, functional overexpresion of FATP1 decreased many aspects of glucose metabolism and diminished CAM-stimulated inflammation in vitro. FATP1 displayed acyl-CoA synthetase activity for long chain fatty acids in M Phi s and modulated lipid mediator metabolism in M Phi s.
Conclusion: Our findings provide evidence that FATP1 is a novel regulator of M Phi activation through control of substrate metabolism. Absence of FATP1 exacerbated pro-inflammatory activation in vitro and increased local and systemic components of the metabolic syndrome in HFD-fed Fatp1(B-/-) mice. In contrast, gain of FATP1 activity in M Phi s suggested that Fatp1-mediated activation of fatty acids, substrate switch to glucose, oxidative stress, and lipid mediator synthesis are potential mechanisms. We demonstrate for the first time that FATP1 provides a unique mechanism by which the inflammatory tone of adipose and systemic metabolism may be regulated. (C) 2016 The Authors. Published by Elsevier GmbH.
C1 [Johnson, Amy R.; Qin, Yuanyuan; Cozzo, Alyssa J.; Freemerman, Alex J.; Huang, Megan J.; Zhao, Liyang; Sampey, Brante P.; Milner, J. Justin; Beck, Melinda A.; Makowski, Liza] Univ N Carolina, Dept Nutr, Gillings Sch Global Publ Hlth, Chapel Hill, NC 27599 USA.
[Beck, Melinda A.; Galanko, Joseph A.; Makowski, Liza] Univ N Carolina, Sch Med, Dept Nutr, Chapel Hill, NC 27599 USA.
[Damania, Blossom] Univ N Carolina, Dept Microbiol & Immunol, Chapel Hill, NC 27599 USA.
[Rashid, Naim] Univ N Carolina, Dept Biostat, Chapel Hill, NC 27599 USA.
[Damania, Blossom; Rashid, Naim; Makowski, Liza] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA.
[Beck, Melinda A.; Galanko, Joseph A.; Makowski, Liza] Univ N Carolina, Nutr Obes Res Ctr, Chapel Hill, NC 27599 USA.
[Lee, Douglas P.] Omic Insight Inc, Durham, NC 27713 USA.
[Edin, Matthew L.; Zeldin, Darryl C.] NIEHS, Div Intramural Res, POB 12233, Res Triangle Pk, NC 27709 USA.
[Fueger, Patrick T.] Indiana Univ Sch Med, Dept Pediat, Indianapolis, IN 46202 USA.
[Fueger, Patrick T.] Indiana Univ Sch Med, Dept Cellular Physiol, Indianapolis, IN 46202 USA.
[Fueger, Patrick T.] Indiana Univ Sch Med, Dept Integrat Physiol, Indianapolis, IN 46202 USA.
[Dietz, Brittney; Stahl, Andreas] Univ Calif Berkeley, Dept Nutr Sci & Toxicol, Berkeley, CA 94720 USA.
[Wu, Ying; Mohlke, Karen L.] Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA.
[Sampey, Brante P.] Roivant Sci Inc, Roviant, NC 27701 USA.
[Milner, J. Justin] Univ Calif San Diego, Div Biol Sci, La Jolla, CA 92093 USA.
RP Makowski, L (reprint author), Univ N Carolina, Dept Nutr, CB7461, Chapel Hill, NC 27599 USA.
EM liza.makowski@unc.edu
FU NCI NIH HHS [P50 CA058223, R01 CA096500]; NHGRI NIH HHS [Z01 HG000024];
NHLBI NIH HHS [F32 HL075970]; NIAAA NIH HHS [K99 AA017376, R00
AA017376]; NIDDK NIH HHS [R01 DK089202, P30 DK034987, P30 DK056350, R01
DK093757, R01 DK099311, U01 DK062370, P30 DK026743, R01 DK062370, R01
DK072193, R01 DK101293, R56 DK062370]; NIEHS NIH HHS [P30 ES010126, Z01
ES025034]
NR 95
TC 2
Z9 2
U1 6
U2 10
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 2212-8778
J9 MOL METAB
JI Mol. Metab.
PD JUL
PY 2016
VL 5
IS 7
BP 506
EP 526
DI 10.1016/j.molmet.2016.04.005
PG 21
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA DP6UK
UT WOS:000378634300009
PM 27408776
ER
PT J
AU Lee, JG
Takahama, S
Zhang, GF
Tomarev, SI
Ye, YH
AF Lee, Jin-Gu
Takahama, Shokichi
Zhang, Guofeng
Tomarev, Stanislav I.
Ye, Yihong
TI Unconventional secretion of misfolded proteins promotes adaptation to
proteasome dysfunction in mammalian cells
SO NATURE CELL BIOLOGY
LA English
DT Article
ID ENDOPLASMIC-RETICULUM; QUALITY CONTROL; NEURODEGENERATIVE DISEASES;
UBIQUITIN LIGASE; ALPHA-SYNUCLEIN; USP19; DEGRADATION; TRANSMISSION;
MECHANISMS; EXOSOMES
AB To safeguard proteomic integrity, cells rely on the proteasome to degrade aberrant polypeptides, but it is unclear how cells remove defective proteins that have escaped degradation owing to proteasome insufficiency or dysfunction. Here we report a pathway termed misfolding-associated protein secretion, which uses the endoplasmic reticulum (ER)-associated deubiquitylase USP19 to preferentially export aberrant cytosolic proteins. Intriguingly, the catalytic domain of USP19 possesses an unprecedented chaperone activity, allowing recruitment of misfolded proteins to the ER surface for deubiquitylation. Deubiquitylated cargos are encapsulated into ER-associated late endosomes and secreted to the cell exterior. USP19-deficient cells cannot efficiently secrete unwanted proteins, and grow more slowly than wild-type cells following exposure to a proteasome inhibitor. Together, our findings delineate a protein quality control (PQC) pathway that, unlike degradation-based PQC mechanisms, promotes protein homeostasis by exporting misfolded proteins through an unconventional protein secretion process.
C1 [Lee, Jin-Gu; Ye, Yihong] NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
[Takahama, Shokichi; Tomarev, Stanislav I.] NEI, Lab Retinal Cell & Mol Biol, NIH, Bethesda, MD 20892 USA.
[Zhang, Guofeng] NIBIB, Biomed Engn & Phys Sci Shared Resource, NIH, Bethesda, MD 20892 USA.
[Takahama, Shokichi] Kumamoto Univ, Matsushita Project Lab, Ctr AIDS Res, Kumamoto 8600811, Japan.
RP Ye, YH (reprint author), NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
EM yihongy@mail.nih.gov
NR 47
TC 13
Z9 13
U1 7
U2 10
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1465-7392
EI 1476-4679
J9 NAT CELL BIOL
JI Nat. Cell Biol.
PD JUL
PY 2016
VL 18
IS 7
BP 765
EP +
DI 10.1038/ncb3372
PG 14
WC Cell Biology
SC Cell Biology
GA DP9TS
UT WOS:000378840900009
PM 27295555
ER
PT J
AU Rich, SS
Wang, ZY
Sturcke, A
Ziyabari, L
Feolo, M
O'Donnell, CJ
Rice, K
Bis, JC
Psaty, BM
AF Rich, Stephen S.
Wang, Zeng Y.
Sturcke, Anne
Ziyabari, Lora
Feolo, Mike
O'Donnell, Christopher J.
Rice, Ken
Bis, Joshua C.
Psaty, Bruce M.
TI Rapid evaluation of phenotypes, SNPs and results through the dbGaP
CHARGE Summary Results site
SO NATURE GENETICS
LA English
DT Letter
ID GENOME-WIDE ASSOCIATION; DESIGN
C1 [Rich, Stephen S.] Univ Virginia, Ctr Publ Hlth Genom, Charlottesville, VA USA.
[Wang, Zeng Y.; Sturcke, Anne; Ziyabari, Lora; Feolo, Mike] US Natl Inst Hlth, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD USA.
[O'Donnell, Christopher J.] NHLBI, Framingham Heart Study, Div Intramural Res, Framingham, MA USA.
[O'Donnell, Christopher J.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA.
[Rice, Ken] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
[Bis, Joshua C.; Psaty, Bruce M.] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA.
[Psaty, Bruce M.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
RP Rich, SS (reprint author), Univ Virginia, Ctr Publ Hlth Genom, Charlottesville, VA USA.
EM ssr4n@virginia.edu
NR 8
TC 2
Z9 2
U1 2
U2 4
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1061-4036
EI 1546-1718
J9 NAT GENET
JI Nature Genet.
PD JUL
PY 2016
VL 48
IS 7
BP 702
EP 703
DI 10.1038/ng.3582
PG 2
WC Genetics & Heredity
SC Genetics & Heredity
GA DP9TK
UT WOS:000378840100002
PM 27350599
ER
PT J
AU Platonov, FA
Tyryshkin, K
Tikhonov, DG
Neustroyeva, TS
Sivtseva, TM
Yakovleva, NV
Nikolaev, VP
Sidorova, OG
Kononova, SK
Goldfarb, LG
Renwick, NM
AF Platonov, Fedor A.
Tyryshkin, Kathrin
Tikhonov, Dmitriy G.
Neustroyeva, Tatyana S.
Sivtseva, Tatyana M.
Yakovleva, Natalya V.
Nikolaev, Valerian P.
Sidorova, Oksana G.
Kononova, Sardana K.
Goldfarb, Lev G.
Renwick, Neil M.
TI Genetic fitness and selection intensity in a population affected with
high-incidence spinocerebellar ataxia type 1
SO NEUROGENETICS
LA English
DT Article
DE Spinocerebellar ataxia type 1; ATXN1 gene; Northeast Siberia;
Sakha(Yakut)population; Genetic fitness; Crow's index
ID CAG-REPEAT; HIGH PREVALENCE; EXPANSION; SIBERIA; DISEASE; ONSET; SCA1;
AGE
AB Spinocerebellar ataxia type 1 (SCA1) is the major and likely the only type of autosomal dominant cerebellar ataxia in the Sakha (Yakut) people of Eastern Siberia. The prevalence rate of SCA1 has doubled over the past 21 years peaking at 46 cases per 100,000 rural population. The age at death correlates closely with the number of CAG triplet repeats in the mutant ATXN1 gene (r = -0.81); most patients with low-medium (39-55) repeat numbers survived until the end of reproductive age. The number of CAG repeats expands in meiosis, particularly in paternal transmissions; the average total increase in intergenerational transmissions in our cohort was estimated at 1.6 CAG repeats. The fertility rates of heterozygous carriers of 39-55 CAG repeats in women were no different from those of the general Sakha population. Overall, the survival of mutation carriers through reproductive age, unaltered fertility rates, low childhood mortality in SCA1-affected families, and intergenerational transmission of increasing numbers of CAG repeats in the ATXN1 gene indicate that SCA1 in the Sakha population will be maintained at high prevalence levels. The low (0.19) Crow's index of total selection intensity in our SCA1 cohort implies that this mutation is unlikely to be eliminated through natural selection alone.
C1 [Platonov, Fedor A.; Tikhonov, Dmitriy G.; Neustroyeva, Tatyana S.; Sivtseva, Tatyana M.; Yakovleva, Natalya V.; Nikolaev, Valerian P.] MK Ammosov North Eastern Fed Univ, Inst Hlth, Yakutsk 677010, Russia.
[Tyryshkin, Kathrin; Renwick, Neil M.] Queens Univ, Dept Pathol & Mol Med, Kingston, ON K7L 3N6, Canada.
[Sidorova, Oksana G.; Kononova, Sardana K.] Acad Med Sci, Ctr Integrated Med Res, Yakutsk 677010, Russia.
[Goldfarb, Lev G.] NINDS, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
RP Goldfarb, LG (reprint author), NINDS, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
EM GoldfarbL@ninds.nih.gov
FU Ministry of Education and Science of the Russian Federation [1742,
18.1742.2014/K, 6.656.2014/K]; Department of Pathology and Molecular
Medicine, Queen's University; Intramural Research Programs of the
National Institute of Neurological Disorders and Stroke; SEAMO New
Clinician-Scientist Investigator Award; Queen's University Principal's
Development Fund
FX The study was funded in part by the Ministry of Education and Science of
the Russian Federation through individual or group projects: PFA-project
1742, TDG, NTS, YNV, and NVP-project 18.1742.2014/K and KSK-project
6.656.2014/K. KT was supported by the Department of Pathology and
Molecular Medicine, Queen's University. GLG was funded in part by the
Intramural Research Programs of the National Institute of Neurological
Disorders and Stroke. NR was funded through a SEAMO New
Clinician-Scientist Investigator Award and the Queen's University
Principal's Development Fund. The authors wish to thank Dr. A. L.
Suhomasova for helpful advice.
NR 28
TC 0
Z9 0
U1 4
U2 4
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1364-6745
EI 1364-6753
J9 NEUROGENETICS
JI Neurogenetics
PD JUL
PY 2016
VL 17
IS 3
BP 179
EP 185
DI 10.1007/s10048-016-0481-5
PG 7
WC Genetics & Heredity; Clinical Neurology
SC Genetics & Heredity; Neurosciences & Neurology
GA DP5NI
UT WOS:000378543900005
PM 27106293
ER
PT J
AU Ghassabian, A
Sundaram, R
Bell, E
Bello, SC
Kus, C
Yeung, E
AF Ghassabian, Akhgar
Sundaram, Rajeshwari
Bell, Erin
Bello, Scott C.
Kus, Christopher
Yeung, Edwina
TI Gross Motor Milestones and Subsequent Development
SO PEDIATRICS
LA English
DT Article
ID AUTISM SPECTRUM DISORDERS; INFANT MOTOR; COGNITIVE FUNCTION; GENERATION
R; BIRTH COHORT; SCHOOL-AGE; ATTAINMENT; LANGUAGE; ABILITIES; TODDLERS
AB OBJECTIVE: We examined the longitudinal associations of age at achieving gross motor milestones and children's development in a US cohort of singletons and twins.
METHODS: In the Upstate KIDS study, a population-based study of children born between 2008 and 2010, information on age at achievement of motor milestones and developmental skills was available in 599 children (314 singletons, 259 twins, and 26 triplets). Mothers reported their children's major motor milestones at similar to 4, 8, 12, 18, and 24 months. At age 4 years, children's development was clinically assessed by using the Battelle Developmental Inventory, Second Edition (BDI-2). Primary analyses by using multivariate linear regressions were conducted in singletons. We also examined the associations in twins.
RESULTS: Later achievement of standing with assistance predicted lower BDI-2 scores in singletons in adjusted models (B per SD of age at achievement, -21.9 [95% confidence interval (CI), -41.5 to -2.2]). Post hoc analysis on age of standing with assistance showed that associations were driven by differences in adaptive skills (B = -5.3 [95% CI, -9.0 to -1.6]) and cognitive skills (B = -5.9 [95% CI, -11.5 to -0.4]). Analyses restricted to twins suggested no association between the age at achievement of milestones and total BDI- 2 score after adjustment for gestational age and birth weight.
CONCLUSIONS: This study provides evidence that the age of achieving motor milestones may be an important basis for various aspects of later child development. In twins, key predictors of later development (eg, perinatal factors) overshadow the predictive role of milestones in infancy.
C1 [Ghassabian, Akhgar; Yeung, Edwina] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Intramural Populat Hlth Res, NIH, Bethesda, MD USA.
[Sundaram, Rajeshwari] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Biostat & Bioinformat Branch, Div Intramural Populat Hlth Res, NIH, Bethesda, MD USA.
[Bell, Erin] SUNY Albany, Dept Environm Hlth Sci, Sch Publ Hlth, Albany, NY 12222 USA.
[Bell, Erin] SUNY Albany, Dept Epidemiol & Biostat, Sch Publ Hlth, Albany, NY 12222 USA.
[Bello, Scott C.] CapitalCare Pediat Troy, Troy, NY USA.
[Kus, Christopher] New York State Dept Hlth, Div Family Hlth, Albany, NY USA.
RP Yeung, E (reprint author), 6100 Execut Blvd,7B03, Bethesda, MD 20892 USA.
EM yeungedw@mail.nih.gov
OI Yeung, Edwina/0000-0002-3851-2613; Sundaram,
Rajeshwari/0000-0002-6918-5002
FU Intramural Research Program of the Eunice Kennedy Shriver National
Institute of Child Health and Human Development [HHSN275201200005C,
HHSN267200700019C]; National Institutes of Health (NIH)
FX Supported by the Intramural Research Program of the Eunice Kennedy
Shriver National Institute of Child Health and Human Development
(HHSN275201200005C and HHSN267200700019C). Funded by the National
Institutes of Health (NIH).
NR 30
TC 0
Z9 0
U1 8
U2 14
PU AMER ACAD PEDIATRICS
PI ELK GROVE VILLAGE
PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA
SN 0031-4005
EI 1098-4275
J9 PEDIATRICS
JI Pediatrics
PD JUL
PY 2016
VL 138
IS 1
AR e20154372
DI 10.1542/peds.2015-4372
PG 8
WC Pediatrics
SC Pediatrics
GA DP9YD
UT WOS:000378853100023
ER
PT J
AU Levy, SJL
Williams, JF
Ryan, SA
Gonzalez, PK
Patrick, SW
Quigley, J
Siqueira, L
Walker, LR
Faden, VB
Tau, G
Jarrett, R
AF Levy, Sharon J. L.
Williams, Janet F.
Ryan, Sheryl A.
Gonzalez, Pamela K.
Patrick, Stephen W.
Quigley, Joanna
Siqueira, Lorena
Walker, Leslie R.
Faden, Vivian B.
Tau, Gregory
Jarrett, Renee
CA Comm Subst Use & Prevention
TI Substance Use Screening, Brief Intervention, and Referral to Treatment
SO PEDIATRICS
LA English
DT Article
AB The enormous public health impact of adolescent substance use and its preventable morbidity and mortality show the need for the health care sector, including pediatricians and the medical home, to increase its capacity related to substance use prevention, detection, assessment, and intervention. The American Academy of Pediatrics published its policy statement "Substance Use Screening, Brief Intervention, and Referral to Treatment for Pediatricians" in 2011 to introduce the concepts and terminology of screening, brief intervention, and referral to treatment (SBIRT) and to offer clinical guidance about available substance use screening tools and intervention procedures. This policy statement is a revision of the 2011 SBIRT statement. An accompanying clinical report updates clinical guidance for adolescent SBIRT.
C1 [Faden, Vivian B.] NIAAA, Bethesda, MD 20892 USA.
[Tau, Gregory] Amer Acad Child & Adolescent Psychiat, Washington, DC USA.
NR 9
TC 0
Z9 0
U1 2
U2 2
PU AMER ACAD PEDIATRICS
PI ELK GROVE VILLAGE
PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA
SN 0031-4005
EI 1098-4275
J9 PEDIATRICS
JI Pediatrics
PD JUL
PY 2016
VL 138
IS 1
AR e20161210
DI 10.1542/peds.2016-1210
PG 3
WC Pediatrics
SC Pediatrics
GA DP9YD
UT WOS:000378853100059
ER
PT J
AU Lowry, JA
Ahdoot, S
Baum, CR
Bernstein, AS
Bole, A
Brumberg, HL
Campbell, CC
Lanphear, BP
Pacheco, SE
Spanier, AJ
Trasande, L
Osterhoudt, KC
Paulson, JA
Sandel, MT
Rogers, PT
Balbus, JM
Brubaker, TA
DeNicola, NG
Etzel, RA
Mortensen, ME
Ward, MH
Spire, P
AF Lowry, Jennifer A.
Ahdoot, Samantha
Baum, Carl R.
Bernstein, Aaron S.
Bole, Aparna
Brumberg, Heather Lynn
Campbell, Carla C.
Lanphear, Bruce Perrin
Pacheco, Susan E.
Spanier, Adam J.
Trasande, Leonardo
Osterhoudt, Kevin C.
Paulson, Jerome A.
Sandel, Megan T.
Rogers, Paul Thomas
Balbus, John M.
Brubaker, Todd A.
DeNicola, Nathaniel G.
Etzel, Ruth Ann
Mortensen, Mary Ellen
Ward, Mary H.
Spire, Paul
TI Prevention of Childhood Lead Toxicity
SO PEDIATRICS
LA English
DT Article
ID ELEVATED BLOOD LEAD; US CHILDREN; EARLY ADULTHOOD; INFANT FORMULA;
UNITED-STATES; EXPOSURE; LEVEL; WATER; DUST; RISK
AB Blood lead concentrations have decreased dramatically in US children over the past 4 decades, but too many children still live in housing with deteriorated lead-based paint and are at risk for lead exposure with resulting lead-associated cognitive impairment and behavioral problems. Evidence continues to accrue that commonly encountered blood lead concentrations, even those below 5 mu g/dL (50 ppb), impair cognition; there is no identified threshold or safe level of lead in blood. From 2007 to 2010, approximately 2.6% of preschool children in the United States had a blood lead concentration >= 5 mu g/dL (>= 50 ppb), which represents about 535 000 US children 1 to 5 years of age. Evidence-based guidance is available for managing increased lead exposure in children, and reducing sources of lead in the environment, including lead in housing, soil, water, and consumer products, has been shown to be cost-beneficial. Primary prevention should be the focus of policy on childhood lead toxicity.
C1 [DeNicola, Nathaniel G.] Amer Coll Obstetricians & Gynecologists, Washington, DC 20024 USA.
[Etzel, Ruth Ann] US Environm Protect Agcy, Washington, DC 20004 USA.
[Mortensen, Mary Ellen] CDC, Natl Ctr Environm Hlth, Atlanta, GA 30333 USA.
[Ward, Mary H.] NCI, Bethesda, MD 20892 USA.
NR 71
TC 0
Z9 0
U1 11
U2 15
PU AMER ACAD PEDIATRICS
PI ELK GROVE VILLAGE
PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA
SN 0031-4005
EI 1098-4275
J9 PEDIATRICS
JI Pediatrics
PD JUL
PY 2016
VL 138
IS 1
AR e20161493
DI 10.1542/peds.2016-1493
PG 15
WC Pediatrics
SC Pediatrics
GA DP9YD
UT WOS:000378853100071
ER
PT J
AU Moeller, SJ
Konova, AB
Tomasi, D
Parvaz, MA
Goldstein, RZ
AF Moeller, Scott J.
Konova, Anna B.
Tomasi, Dardo
Parvaz, Muhammad A.
Goldstein, Rita Z.
TI Abnormal response to methylphenidate across multiple fMRI procedures in
cocaine use disorder: feasibility study
SO PSYCHOPHARMACOLOGY
LA English
DT Article
DE Addiction; ADHD; Brain imaging; Cerebral cortex; Cocaine; Dopamine;
FMRI; Inhibition; Psychostimulant; Working memory
ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; DEFICIT HYPERACTIVITY
DISORDER; DORSOLATERAL PREFRONTAL CORTEX; TRAUMATIC BRAIN-INJURY;
WORKING-MEMORY; FUNCTIONAL CONNECTIVITY; INHIBITORY CONTROL; DEPENDENT
PATIENTS; INTERFERENCE TASK; ADDICTION
AB Rationale The indirect dopamine agonist methylphenidate remediates cognitive deficits in psychopathology, but the individual characteristics that determine its effects on the brain are not known.
Objectives We aimed to determine whether targeted dopaminergically modulated traits and individual differences could predict neural response to methylphenidate across multiple functional magnetic resonance imaging (fMRI) procedures.
Methods We combined neural measures from three separate procedures (two inhibitory control tasks differing in their degree of emotional salience and resting-state functional connectivity) during methylphenidate (20 mg oral, versus randomized and counterbalanced placebo) and correlated these aggregated responses with cocaine use disorder diagnosis (22 cocaine abusers, 21 controls), symptoms of attention deficit hyperactivity disorder, and working memory capacity.
Results Cocaine abusers, relative to controls, had a lower response in the dorsolateral prefrontal cortex to methylphenidate across all three procedures, driven by responses to the two inhibitory control tasks; reduced methylphenidate fMRI response in this region further correlated with more frequent cocaine use.
Conclusions Cocaine abuse (and its frequency), associated with lower tonic dopamine levels, correlated with a reduction in activation to methylphenidate (versus placebo). These initial results provide feasibility to the idea that multimodal fMRI tasks can be meaningfully aggregated, and that these aggregated procedures show a common disruption in addiction in a highly anticipated region relevant to cognitive control. Results also suggest that drug use frequency may represent an important modulatory variable in interpreting the efficacy of pharmacologically enhanced cognitive interventions in addiction.
C1 [Moeller, Scott J.; Parvaz, Muhammad A.; Goldstein, Rita Z.] Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA.
[Moeller, Scott J.; Parvaz, Muhammad A.; Goldstein, Rita Z.] Icahn Sch Med Mt Sinai, Dept Neurosci, New York, NY 10029 USA.
[Moeller, Scott J.] 1470 Madison Ave Room 9-115, New York, NY 10029 USA.
[Konova, Anna B.] NYU, Ctr Neural Sci, New York, NY 10003 USA.
[Tomasi, Dardo] NIAAA, Bethesda, MD 20892 USA.
[Goldstein, Rita Z.] One Gustave L Levy Pl,Box 1230, New York, NY 10029 USA.
RP Moeller, SJ; Goldstein, RZ (reprint author), Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA.; Moeller, SJ; Goldstein, RZ (reprint author), Icahn Sch Med Mt Sinai, Dept Neurosci, New York, NY 10029 USA.; Moeller, SJ (reprint author), 1470 Madison Ave Room 9-115, New York, NY 10029 USA.; Goldstein, RZ (reprint author), One Gustave L Levy Pl,Box 1230, New York, NY 10029 USA.
EM scott.moeller@mssm.edu; rita.goldstein@mssm.edu
RI Moeller, Scott/L-5549-2016;
OI Moeller, Scott/0000-0002-4449-0844; Parvaz, Muhammad/0000-0002-2671-2327
FU National Institute on Drug Abuse [R01DA023579, F32DA030017, K01DA037452,
F32DA039648, F32DA033088]
FX This study was supported by grants from the National Institute on Drug
Abuse (to RZG: R01DA023579; to SJM: F32DA030017, K01DA037452; to ABK:
F32DA039648; to MAP: F32DA033088). The content is solely the
responsibility of the authors and does not necessarily represent the
official views of the National Institutes of Health. We also thank Dr.
Elena Shumay, whom the scientific community has lost too prematurely,
for help with analyses in earlier versions of this manuscript.
NR 68
TC 0
Z9 0
U1 1
U2 1
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0033-3158
EI 1432-2072
J9 PSYCHOPHARMACOLOGY
JI Psychopharmacology
PD JUL
PY 2016
VL 233
IS 13
BP 2559
EP 2569
DI 10.1007/s00213-016-4307-9
PG 11
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA DP5ZE
UT WOS:000378575900014
PM 27150080
ER
PT J
AU Sampath, SC
Sampath, SC
Bredella, MA
Cypess, AM
Torriani, M
AF Sampath, Srihari C.
Sampath, Srinath C.
Bredella, Miriam A.
Cypess, Aaron M.
Torriani, Martin
TI Imaging of Brown Adipose Tissue: State of the Art
SO RADIOLOGY
LA English
DT Article
ID IN-VIVO; GLUCOSE-UPTAKE; COLD-EXPOSURE; ADULT HUMANS;
ENERGY-EXPENDITURE; BLOOD-FLOW; FDG UPTAKE; CONTRAST ULTRASOUND; BEIGE
ADIPOCYTES; FAT-CELLS
AB The rates of diabetes, obesity, and metabolic disease have reached epidemic proportions worldwide. In recent years there has been renewed interest in combating these diseases not only by modifying energy intake and lifestyle factors, but also by inducing endogenous energy expenditure. This approach has largely been stimulated by the recent recognition that brown adipose tissue (BAT)-long known to promote heat production and energy expenditure in infants and hibernating mammals-also exists in adult humans. This landmark finding relied on the use of clinical fluorine 18 fluorodeoxyglucose positron emission tomography/computed tomography, and imaging techniques continue to play a crucial and increasingly central role in understanding BAT physiology and function. Herein, the authors review the origins of BAT imaging, discuss current preclinical and clinical strategies for imaging BAT, and discuss imaging methods that will provide crucial insight into metabolic disease and how it may be treated by modulating BAT activity. (C) RSNA, 2016
C1 [Sampath, Srihari C.; Sampath, Srinath C.] Novartis Res Fdn, Genom Inst, Dept Pharmacol, Musculoskeletal Biol & Bioimaging, San Diego, CA USA.
[Bredella, Miriam A.; Torriani, Martin] Massachusetts Gen Hosp, Div Musculoskeletal Imaging & Intervent, 55 Fruit St,Yawkey 6E, Boston, MA 02114 USA.
[Bredella, Miriam A.; Torriani, Martin] Harvard Univ, Sch Med, 55 Fruit St,Yawkey 6E, Boston, MA 02114 USA.
[Cypess, Aaron M.] NIDDK, Translat Physiol Sect, Diabet Endocrinol & Obes Branch, NIH, Bethesda, MD 20892 USA.
RP Torriani, M (reprint author), Massachusetts Gen Hosp, Div Musculoskeletal Imaging & Intervent, 55 Fruit St,Yawkey 6E, Boston, MA 02114 USA.; Torriani, M (reprint author), Harvard Univ, Sch Med, 55 Fruit St,Yawkey 6E, Boston, MA 02114 USA.
EM mtor-riani@mgh.harvard.edu
FU Chugai Pharma; Molecular Metabolism; Pfizer
FX Srihari C. Sampath Activities related to the present article: disclosed
no relevant relationships. Activities not related to the present
article: is an employee of the Genomics Institute of the Novartis
Research Foundation, part of the Novartis Institutes for Biomedical
Research. Other relationships: disclosed no relevant relationships.
Srinath C. Sampath Activities related to the present article: disclosed
no relevant relationships. Activities not related to the present
article: is an employee of the Genomics Institute of the Novartis
Research Foundation, part of the Novartis Institutes for Biomedical
Research. Other relationships: disclosed no relevant relationships. M.B.
disclosed no relevant relationships. A.M.C. Activities related to the
present article: disclosed no relevant relationships. Activities not
related to the present article: received grants from Chugai Pharma and
Molecular Metabolism; received personal fees from Pfizer. Other
relationships: disclosed no relevant relationships. M.T. disclosed no
relevant relationships.
NR 100
TC 1
Z9 1
U1 11
U2 11
PU RADIOLOGICAL SOC NORTH AMERICA
PI OAK BROOK
PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA
SN 0033-8419
J9 RADIOLOGY
JI Radiology
PD JUL
PY 2016
VL 280
IS 1
BP 4
EP 19
DI 10.1148/radiol.2016150390
PG 16
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA DP8BC
UT WOS:000378721900002
PM 27322970
ER
PT J
AU Gibson, BA
Zhang, YJ
Jiang, H
Hussey, KM
Shrimp, JH
Lin, HN
Schwede, F
Yu, YH
Kraus, WL
AF Gibson, Bryan A.
Zhang, Yajie
Jiang, Hong
Hussey, Kristine M.
Shrimp, Jonathan H.
Lin, Hening
Schwede, Frank
Yu, Yonghao
Kraus, W. Lee
TI Chemical genetic discovery of PARP targets reveals a role for PARP-1 in
transcription elongation
SO SCIENCE
LA English
DT Article
ID ADP-RIBOSYLATION; RNA; POLY(ADP-RIBOSE); LOCI; PROMOTERS; BINDING
AB Poly[adenosine diphosphate (ADP)-ribose] polymerases (PARPs) are a family of enzymes that modulate diverse biological processes through covalent transfer of ADP-ribose from the oxidized form of nicotinamide adenine dinucleotide (NAD(+)) onto substrate proteins. Here we report a robust NAD(+) analog-sensitive approach for PARPs, which allows PARP-specific ADP-ribosylation of substrates that is suitable for subsequent copper-catalyzed azide-alkyne cycloaddition reactions. Using this approach, we mapped hundreds of sites of ADP-ribosylation for PARPs 1, 2, and 3 across the proteome, as well as thousands of PARP-1-mediated ADP-ribosylation sites across the genome. We found that PARP-1 ADP-ribosylates and inhibits negative elongation factor (NELF), a protein complex that regulates promoter-proximal pausing by RNA polymerase II (Pol II). Depletion or inhibition of PARP-1 or mutation of the ADP-ribosylation sites on NELF-E promotes Pol II pausing, providing a clear functional link between PARP-1, ADP-ribosylation, and NELF. This analog-sensitive approach should be broadly applicable across the PARP family and has the potential to illuminate the ADP-ribosylated proteome and the molecular mechanisms used by individual PARPs to mediate their responses to cellular signals.
C1 [Gibson, Bryan A.; Kraus, W. Lee] Univ Texas SW Med Ctr Dallas, Lab Signaling & Gene Express, Cecil H & Ida Green Ctr Reprod Biol Sci, Dallas, TX 75390 USA.
[Gibson, Bryan A.; Kraus, W. Lee] Univ Texas SW Med Ctr Dallas, Basic Res Div, Dept Obstet & Gynecol, Dallas, TX 75390 USA.
[Zhang, Yajie; Yu, Yonghao] Univ Texas SW Med Ctr Dallas, Dept Biochem, Dallas, TX 75390 USA.
[Jiang, Hong; Shrimp, Jonathan H.; Lin, Hening] Cornell Univ, Howard Hughes Med Inst, Ithaca, NY 14850 USA.
[Jiang, Hong; Shrimp, Jonathan H.; Lin, Hening] Cornell Univ, Dept Chem, Ithaca, NY 14850 USA.
[Hussey, Kristine M.] Sarepta Therapeut, Cambridge, MA 02142 USA.
[Schwede, Frank] Biolog Life Sci Inst, D-28199 Bremen, Germany.
[Jiang, Hong] Chinese Acad Sci, Shanghai Inst Organ Chem, Interdisciplinary Res Ctr Biol & Chem, Shanghai 201203, Peoples R China.
[Shrimp, Jonathan H.] NCI, Biol Chem Lab, Ctr Canc Res, Frederick, MD 21702 USA.
RP Kraus, WL (reprint author), Univ Texas SW Med Ctr Dallas, Lab Signaling & Gene Express, Cecil H & Ida Green Ctr Reprod Biol Sci, Dallas, TX 75390 USA.; Kraus, WL (reprint author), Univ Texas SW Med Ctr Dallas, Basic Res Div, Dept Obstet & Gynecol, Dallas, TX 75390 USA.
EM lee.kraus@utsouthwestern.edu
FU American Heart Association; Cancer Prevention and Research Institute of
Texas [CPRIT R1103]; Welch Foundation [I-1800]; UT Southwestern Endowed
Scholars Program; NIH National Institute of General Medical Sciences
[GM086703]; NIH National Institute of Diabetes and Digestive and Kidney
Diseases [DK069710]; Cecil H. and Ida Green Center for Reproductive
Biology Sciences Endowments
FX We thank M. Chae, Q. Liang, J. DeBrabander, U. Havemann, and D. Imren
for technical assistance and members of the Kraus laboratory for helpful
discussions about this project. The asPARP expression constructs and the
NAD+ analogs can be obtained from University of Texas (UT)
Southwestern Medical Center and Biolog Life Science Institute,
respectively, under a material transfer agreement. W.L.K., B.A.G., F.S.,
and H.L. are inventors on U.S. patent application no. 62/144,711, filed
by UT Southwestern Medical Center, related to the asPARP technology.
W.L.K. and B.A.G. are inventors on U.S. patent application nos.
62/009,955 and PCT/US2015/034852, filed by UT Southwestern Medical
Center, related to the ADP-ribose detection reagents. Y.Y. is an
inventor on U.S. patent no. 8828672 B2, filed by UT Southwestern Medical
Center, related to technology for the determination of
D/E-ADP-ribosylation sites. This work was supported by a predoctoral
fellowship from the American Heart Association to B.A.G.; grants from
the Cancer Prevention and Research Institute of Texas (CPRIT R1103), the
Welch Foundation (I-1800), and the UT Southwestern Endowed Scholars
Program to Y.Y., who is the Virginia Murchison Linthicum Scholar in
Medical Research and a CPRIT Scholar in Cancer Research; a grant from
the NIH National Institute of General Medical Sciences (GM086703) to
H.L.; and a grant from the NIH National Institute of Diabetes and
Digestive and Kidney Diseases (DK069710) and support from the Cecil H.
and Ida Green Center for Reproductive Biology Sciences Endowments to
W.L.K. W.L.K. is a founder and consultant for Ribon Therapeutics. The
genomic data sets from this study are available from the National Center
for Biotechnology Information Gene Expression Omnibus database under
accession numbers GSE74141 (ChIP-seq) and GSE74142 (GRO-seq and
RNA-seq). The proteomic data sets generated for these studies are
available in table S1. Author contributions: On the basis of (7), B.A.G.
conceived the asPARP concept, with input from W.L.K. W.L.K. conceived
the Click-ChIP-seq method, which was further developed by B.A.G. B.A.G.
performed all experiments and computational analyses, except as follows:
H. J., J. H. S., H.L., and F.S. synthesized all precursors and NAD+
analogs used in this study. B.A.G. and H. J. performed the enzyme
kinetics assays. B.A.G., Y.Z., and Y.Y. prepared the samples and ran the
LC-MS/MS analysis. K.M.H. made the PARP-1 knockdown MCF-7 cells and
prepared the GRO-seq samples. W.L.K. secured funding to support this
project and provided intellectual support for all aspects of the work.
B.A.G. and W.L.K. prepared the figures and wrote the paper.
NR 19
TC 19
Z9 19
U1 13
U2 20
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 0036-8075
EI 1095-9203
J9 SCIENCE
JI Science
PD JUL 1
PY 2016
VL 353
IS 6294
BP 45
EP 50
DI 10.1126/science.aaf7865
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DP9KX
UT WOS:000378816200031
PM 27256882
ER
PT J
AU Kim, S
Zhao, YY
Lee, JM
Kim, WR
Gorivodsky, M
Westphal, H
Geum, D
AF Kim, Soojin
Zhao, Yangu
Lee, Ja-myong
Kim, Woon Ryoung
Gorivodsky, Marat
Westphal, Heiner
Geum, Dongho
TI Ldb1 Is Essential for the Development of Isthmic Organizer and Midbrain
Dopaminergic Neurons
SO STEM CELLS AND DEVELOPMENT
LA English
DT Article
ID LIM-HOMEODOMAIN PROTEINS; EMBRYONIC STEM-CELLS; INT-1 PROTOONCOGENE;
CHOLINERGIC NEURONS; WNT1 EXPRESSION; LMX1B; MOUSE; DIFFERENTIATION;
GENE; CEREBELLUM
AB LIM domain-binding protein 1 (Ldb1) is a nuclear cofactor that interacts with LIM homeodomain proteins to form multiprotein complexes that are important for transcription regulation. Ldb1 has been shown to play essential roles in various processes during mouse embryogenesis. To determine the role of Ldb1 in mid-and hindbrain development, we have generated a conditional mutant with a specific deletion of the Ldb1 in the Engrailed-1-expressing region of the developing mid-and hindbrain. Our study showed that the deletion impaired the expression of signaling molecules, such as fibroblast growth factor 8 (FGF8) and Wnt1, in the isthmic organizer and the expression of Shh in the ventral midbrain. The midbrain and the cerebellum were severely reduced in size, and the midbrain dopaminergic (mDA) neurons were missing in the mutant. These defects are identical to the phenotype that has been observed previously in mice with a deletion of the LIM homeodomain gene Lmx1b. Our results thus provide genetic evidence supporting that Ldb1 and Lmx1b function cooperatively to regulate mid-and hindbrain development. In addition, we found that mouse embryonic stem cells lacking Ldb1 failed to generate several types of differentiated neurons, including the mDA neurons, serotonergic neurons, cholinergic neurons, and olfactory bulb neurons, indicating an essential cell-autonomous role for Ldb1 in the development of these neurons.
C1 [Kim, Soojin; Lee, Ja-myong; Kim, Woon Ryoung; Geum, Dongho] Korea Univ, Sch Med, Dept Biomed Sci, Seoul 136705, South Korea.
[Zhao, Yangu; Gorivodsky, Marat; Westphal, Heiner] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Genom Differentiat, NIH, Bethesda, MD USA.
[Zhao, Yangu] NIDDK, Lab Cellular Dev Biol, NIH, Bethesda, MD 20892 USA.
RP Geum, D (reprint author), Korea Univ, Sch Med, Dept Biomed Sci, Seoul 136705, South Korea.; Zhao, YY (reprint author), NIDDK, NIH, Bethesda, MD 20892 USA.
EM zhaoyang@mail.nih.gov; geumd@korea.ac.kr
FU Korea Health Technology R&D Project through the Korea Health Industry
Development Institute - Ministry of Health & Welfare, Republic of Korea
[HI14C3347]; National Research Foundation of Korea
[NRF-2012M3A9C7050135]; NICHD/NIH
FX The authors would like to thank Dr. Wolfgang Wurst for providing the
En1Cre mice, Dr. Andrew McMahon for providing the probes of
Shh and Wnt1 for in situ hybridization, and Dr. Paul Love for providing
the Ldb1 antibody. This work was supported by a grant of the Korea
Health Technology R&D Project through the Korea Health Industry
Development Institute, funded by the Ministry of Health & Welfare,
Republic of Korea (grant number HI14C3347), the National Research
Foundation of Korea (NRF-2012M3A9C7050135), and the Intramural Research
Program of the NICHD/NIH.
NR 40
TC 0
Z9 0
U1 1
U2 1
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1547-3287
EI 1557-8534
J9 STEM CELLS DEV
JI Stem Cells Dev.
PD JUL 1
PY 2016
VL 25
IS 13
BP 986
EP 994
DI 10.1089/scd.2015.0307
PG 9
WC Cell & Tissue Engineering; Hematology; Medicine, Research &
Experimental; Transplantation
SC Cell Biology; Hematology; Research & Experimental Medicine;
Transplantation
GA DP7BP
UT WOS:000378654300003
PM 27171818
ER
PT J
AU Kringelbach, ML
Stark, EA
Alexander, C
Bornstein, MH
Stein, A
AF Kringelbach, Morten L.
Stark, Eloise A.
Alexander, Catherine
Bornstein, Marc H.
Stein, Alan
TI On Cuteness: Unlocking the Parental Brain and Beyond
SO TRENDS IN COGNITIVE SCIENCES
LA English
DT Review
ID HUMAN ORBITOFRONTAL CORTEX; INFANT FACES; POSTNATAL DEPRESSION; BABY
SCHEMA; FUNCTIONAL NEUROANATOMY; POSTPARTUM DEPRESSION; MATERNAL
SENSITIVITY; PERCEIVED CUTENESS; ATTACHMENT; RESPONSES
AB Cuteness in offspring is a potent protective mechanism that ensures survival for otherwise completely dependent infants. Previous research has linked cuteness to early ethological ideas of a 'Kindchenschema' (infant schema) where infant facial features serve as 'innate releasing mechanisms' for instinctual caregiving behaviours. We propose extending the concept of cuteness beyond visual features to include positive infant sounds and smells. Evidence from behavioural and neuroimaging studies links this extended concept of cuteness to simple 'instinctual' behaviours and to caregiving, protection, and complex emotions. We review how cuteness supports key parental capacities by igniting fast privileged neural activity followed by slower processing in large brain networks also involved in play, empathy, and perhaps even higher-order moral emotions.
C1 [Kringelbach, Morten L.; Stark, Eloise A.; Alexander, Catherine; Stein, Alan] Univ Oxford, Dept Psychiat, Oxford OX3 7JX, England.
[Kringelbach, Morten L.; Alexander, Catherine] Aarhus Univ, Ctr Mus Brain MIB, Aarhus, Denmark.
[Bornstein, Marc H.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Suite 8030,6705 Rockledge Dr, Bethesda, MD 20892 USA.
RP Kringelbach, ML (reprint author), Univ Oxford, Dept Psychiat, Oxford OX3 7JX, England.; Kringelbach, ML (reprint author), Aarhus Univ, Ctr Mus Brain MIB, Aarhus, Denmark.
EM morten.kringelbach@psych.ox.ac.uk
OI Kringelbach, Morten/0000-0002-3908-6898
FU ERC [615539]; MRC; Wellcome Trust [090139]; Intramural Research Program
of the NIH, NICHD; Barclay Foundation; Center for Music in the Brain at
Aarhus University - Danish National Research Foundation [DNRF117]
FX The research was supported by an ERC Consolidator Grant CAREGIVING (No.
615539) to M.L.K.; an MRC Studentship awarded to E.A.S.; a Wellcome
Trust Grant (No. 090139) to A.S. M.H.B. was supported by the Intramural
Research Program of the NIH, NICHD. Furthermore the research was
supported by the Barclay Foundation to M.L.K. and A.S., as well as the
Center for Music in the Brain at Aarhus University funded by the Danish
National Research Foundation (DNRF117) to M.L.K.
NR 114
TC 2
Z9 2
U1 22
U2 35
PU ELSEVIER SCIENCE LONDON
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 1364-6613
J9 TRENDS COGN SCI
JI TRENDS COGN. SCI.
PD JUL
PY 2016
VL 20
IS 7
BP 545
EP 558
DI 10.1016/j.tics.2016.05.003
PG 14
WC Behavioral Sciences; Neurosciences; Psychology, Experimental
SC Behavioral Sciences; Neurosciences & Neurology; Psychology
GA DQ3MJ
UT WOS:000379106100009
PM 27211583
ER
PT J
AU Wu, J
Liu, Q
Tang, P
Mikkelsen, JD
Shen, JX
Whiteaker, P
Yakel, JL
AF Wu, Jie
Liu, Qiang
Tang, Pei
Mikkelsen, Jens D.
Shen, Jianxin
Whiteaker, Paul
Yakel, Jerrel L.
TI Heteromeric alpha 7 beta 2 Nicotinic Acetylcholine Receptors in the
Brain
SO TRENDS IN PHARMACOLOGICAL SCIENCES
LA English
DT Review
ID XENOPUS-LAEVIS OOCYTES; ALPHA-BUNGAROTOXIN; PHARMACOLOGICAL
CHARACTERIZATION; HIPPOCAMPAL-NEURONS; CHOLINERGIC NEURONS;
HIGH-SENSITIVITY; BETA-2 SUBUNITS; ACH RECEPTORS; BINDING-SITE;
RAT-BRAIN
AB The alpha 7 nicotinic acetylcholine receptor (alpha 7 nAChR) is highly expressed in the brain, where it maintains various neuronal functions including (but not limited to) learning and memory. In addition, the protein expression levels of alpha 7 nAChRs are altered in various brain disorders. The classic rule governing alpha 7 nAChR assembly in the mammalian brain was that it was assembled from five alpha 7 subunits to form a homomeric receptor pentamer. However, emerging evidence demonstrates the presence of heteromeric alpha 7 nAChRs in heterologously expressed systems and naturally in brain neurons, where alpha 7 subunits are co-assembled with beta 2 subunits to form a novel type of alpha 7 beta 2 nAChR. Interestingly, the alpha 7 beta 2 nAChR exhibits distinctive function and pharmacology from traditional homomeric alpha 7 nAChRs. We review recent advances in probing the distribution, function, pharmacology, pathophysiology, and stoichiometry of the heteromeric alpha 7 beta 2 nAChR, which have provided, new insights into the understanding of a novel target of cholinergic signaling.
C1 [Wu, Jie; Shen, Jianxin] Shantou Univ, Dept Physiol, Coll Med, Shantou, Guangdong, Peoples R China.
[Wu, Jie; Liu, Qiang; Whiteaker, Paul] St Josephs Hosp, Barrow Neurol Inst, Div Neurol, Phoenix, AZ 85013 USA.
[Wu, Jie; Liu, Qiang; Whiteaker, Paul] St Josephs Hosp, Barrow Neurol Inst, Div Neurobiol, Phoenix, AZ 85013 USA.
[Tang, Pei] Univ Pittsburgh, Sch Med, Dept Anesthesiol, Pittsburgh, PA 15260 USA.
[Mikkelsen, Jens D.] Rigshosp, Univ Copenhagen Hosp, Neurobiol Res Unit, Copenhagen, Denmark.
[Yakel, Jerrel L.] NIEHS, Neurobiol Lab, NIH, DHHS, POB 12233, Res Triangle Pk, NC 27709 USA.
RP Wu, J (reprint author), Shantou Univ, Dept Physiol, Coll Med, Shantou, Guangdong, Peoples R China.; Wu, J (reprint author), St Josephs Hosp, Barrow Neurol Inst, Div Neurol, Phoenix, AZ 85013 USA.; Wu, J (reprint author), St Josephs Hosp, Barrow Neurol Inst, Div Neurobiol, Phoenix, AZ 85013 USA.
EM jie.wu@dignityhealth.org
FU Barrow Neuroscience Foundation; Arizona Alzheimer Disease Consortium;
NIH [R01GM66358, R01GM56257, R21DA026627]; Intramural Research Program,
NIEHS/NIH; Innovation Fund in Denmark, COGNITO; National Natural Science
Foundation of China [31171089]
FX This work was supported by grants from the Barrow Neuroscience
Foundation to J.W. and P.W., Arizona Alzheimer Disease Consortium to
J.W. and Q.L., NIH (R01GM66358 and R01GM56257) to P.T., NIH
(R21DA026627) to P.W., the Intramural Research Program, NIEHS/NIH to
J.L.Y., the Innovation Fund in Denmark, COGNITO to J.D.M., and National
Natural Science Foundation of China (No. 31171089) to J.X.S.
NR 66
TC 6
Z9 7
U1 3
U2 10
PU ELSEVIER SCIENCE LONDON
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 0165-6147
J9 TRENDS PHARMACOL SCI
JI Trends Pharmacol. Sci.
PD JUL
PY 2016
VL 37
IS 7
BP 562
EP 574
DI 10.1016/j.tips.2016.03.005
PG 13
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA DQ1LC
UT WOS:000378961500005
PM 27179601
ER
PT J
AU Brennan, CW
Kelly, B
Skarf, LM
Tellem, R
Dunn, KM
Poswolsky, S
AF Brennan, Caitlin W.
Kelly, Brittany
Skarf, Lara Michal
Tellem, Rotem
Dunn, Kathleen M.
Poswolsky, Sheila
TI Improving Palliative Care Team Meetings: Structure, Inclusion, and "Team
Care"
SO AMERICAN JOURNAL OF HOSPICE & PALLIATIVE MEDICINE
LA English
DT Article
DE palliative care; interprofessional; team meeting; quality improvement;
model for improvement; efficiency
ID COMMUNICATION
AB Increasing demands on palliative care teams point to the need for continuous improvement to ensure teams are working collaboratively and efficiently. This quality improvement initiative focused on improving interprofessional team meeting efficiency and subsequently patient care. Meeting start and end times improved from a mean of approximately 9 and 6 minutes late in the baseline period, respectively, to a mean of 4.4 minutes late (start time) and ending early in our sustainability phase. Mean team satisfaction improved from 2.4 to 4.5 on a 5-point Likert-type scale. The improvement initiative clarified communication about patients' plans of care, thus positively impacting team members' ability to articulate goals to other professionals, patients, and families. We propose several recommendations in the form of a team meeting toolkit.
C1 [Brennan, Caitlin W.] NIH, Ctr Clin, Dept Nursing, Res & Practice Dev Sect, 10 Ctr Dr,Suite 2B,Room 08, Bethesda, MD 20892 USA.
[Brennan, Caitlin W.; Kelly, Brittany; Skarf, Lara Michal; Tellem, Rotem; Dunn, Kathleen M.; Poswolsky, Sheila] Vet Affairs Boston Healthcare Syst, Jamaica Plain, MA USA.
RP Brennan, CW (reprint author), NIH, Ctr Clin, Dept Nursing, Res & Practice Dev Sect, 10 Ctr Dr,Suite 2B,Room 08, Bethesda, MD 20892 USA.
EM caitlin.brennan@nih.gov
NR 11
TC 0
Z9 0
U1 0
U2 2
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1049-9091
EI 1938-2715
J9 AM J HOSP PALLIAT ME
JI Am. J. Hosp. Palliat. Med.
PD JUL
PY 2016
VL 33
IS 6
BP 585
EP 593
DI 10.1177/1049909115577049
PG 9
WC Health Care Sciences & Services
SC Health Care Sciences & Services
GA DP3NJ
UT WOS:000378401100010
PM 25794871
ER
PT J
AU Goldberg, RB
Bittner, VA
Dunbar, RL
Fleg, JL
Grunberger, G
Guyton, JR
Leiter, LA
McBride, R
Robinson, JG
Simmons, DL
Wysham, C
Xu, P
Boden, WE
AF Goldberg, Ronald B.
Bittner, Vera A.
Dunbar, Richard L.
Fleg, Jerome L.
Grunberger, George
Guyton, John R.
Leiter, Lawrence A.
McBride, Ruth
Robinson, Jennifer G.
Simmons, Debra L.
Wysham, Carol
Xu, Ping
Boden, William E.
TI Effects of Extended-Release Niacin Added to Simvastatin/Ezetimibe on
Glucose and Insulin Values in AIM-HIGH
SO AMERICAN JOURNAL OF MEDICINE
LA English
DT Article
DE Clinical trial; Diabetes; Extended release niacin; Glucose and insulin;
Heart disease; Impaired fasting glucoses
ID IMPAIRED FASTING GLUCOSE; CORONARY-ARTERY-DISEASE; CARDIOVASCULAR
EVENTS; METABOLIC SYNDROME; NICOTINIC-ACID; THERAPY; TRIAL; CHOLESTEROL;
TOLERANCE; HEALTH
AB BACKGROUND: Niacin is an antidyslipidemic agent that may cause blood sugar elevation in patients with diabetes, but its effects on glucose and insulin values in nondiabetic statin-treated subjects with cardiovascular disease and at high risk for diabetes are less well known.
METHODS: This was a prespecified, intent-to-treat analysis of the Atherothrombosis Intervention in Metabolic syndrome with low high-density lipoprotein/high triglycerides: Impact on Global Health outcomes trial which randomized 3,414 participants at 92 centers in the US and Canada to extended-release niacin (ERN) plus simvastatin/ezetimibe (ERN) or simvastatin/ezetimibe plus placebo (Placebo). Baseline and annual fasting glucose and insulin values were measured. Those experiencing an adverse event indicative of diabetes or starting medications for diabetes were considered to have confirmed diabetes. In addition, nondiabetic subjects with 2 annual follow-up glucose measurements were categorized into normal, impaired fasting glucose or newly diagnosed diabetes (presumed or confirmed) states.
RESULTS: Compared with placebo, ERN increased annual fasting glucose from baseline to 1 year in both those with normal (7.9 +/- 15.8 vs 4.3 +/- 10.3 mg/dL; P < .001) and impaired fasting glucose (4.1 +/- 18.7 vs 1.4 +/- 14.9; P < .02) and increased insulin levels. Both effectswaned over the next 2 years. There were less consistent effects in those with baseline diabetes. There was an increased risk of progressing from normal to presumed or confirmed impaired fasting glucose (ERN 197/336) cases (58.6%) vs placebo 135/325 cases (41.5%; P < .001) over time, but no difference in diabetes development in the 2 treatment groups except in those with normal fasting glucose at baseline.
CONCLUSIONS: The addition of ERN to simvastatin/ezetimibe had marginal effects on glycemia in those with diabetes at baseline, and there was a trend toward increased development of new-onset diabetes. In addition, ERN increased the risk of developing impaired fasting glucose, which may have deleterious consequences over time and warrants further study. (C) 2016 Elsevier Inc. All rights reserved.
C1 [Goldberg, Ronald B.] Univ Miami, Miller Sch Med, Div Endocrinol Metab & Diabet, Coral Gables, FL 33124 USA.
[Bittner, Vera A.] Univ Alabama, Birmingham Sch Med, Dept Med, Div Cardiovasc Dis, Tuscaloosa, AL 35487 USA.
[Dunbar, Richard L.] Univ Penn, Perelman Sch Med, Dept Med, Div Translat Med & Human Genet, Philadelphia, PA 19104 USA.
[Fleg, Jerome L.] NHLBI, Div Cardiovasc Sci, Bldg 10, Bethesda, MD 20892 USA.
[Grunberger, George] Grunberger Diabet Inst, Bloomfield Hills, MI USA.
[Guyton, John R.] Duke Univ, Med Ctr, Durham, NC USA.
[Leiter, Lawrence A.] St Michaels Hosp, Keenan Res Ctr, Li Ka Shing Knowledge Inst, Div Endocrinol & Metab, 30 Bond St, Toronto, ON M5B 1W8, Canada.
[McBride, Ruth] Axio Res LLC, 2601 Fourth Ave,Suite 200, Seattle, WA 98121 USA.
[Robinson, Jennifer G.] Univ Iowa, Coll Publ Hlth, Iowa City, IA USA.
[Robinson, Jennifer G.] Univ Iowa, Carver Coll Med, Iowa City, IA USA.
[Simmons, Debra L.] Univ Utah, Dept Internal Med, Div Endocrinol, Salt Lake City, UT 84112 USA.
[Wysham, Carol] Rockwood Diabet & Endocrinol, Spokane, WA USA.
[Xu, Ping] PPD, Wilmington, NC USA.
[Boden, William E.] Albany VA Med Ctr, Dept Med, Albany, NY 12208 USA.
RP McBride, R (reprint author), Axio Res LLC, 2601 Fourth Ave,Suite 200, Seattle, WA 98121 USA.
EM ruthm@axioresearch.com
FU National Heart, Lung, and Blood Institute [U01 HL081616, U01 HL081649];
AbbVie, Inc.
FX The Atherothrombosis Intervention in Metabolic syndrome with low
high-density lipoprotein/high triglycerides: Impact on Global Health
(AIM-HIGH) study was supported by the National Heart, Lung, and Blood
Institute (U01 HL081616 and U01 HL081649) and by an unrestricted grant
from AbbVie, Inc. AbbVie donated the extended-release niacin, the
matching placebo, and the ezetimibe; Merck donated the simvastatin.
Neither of these companies had any role in the oversight or design of
the study or in the analysis or interpretation of the data.
NR 21
TC 0
Z9 0
U1 5
U2 8
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9343
EI 1555-7162
J9 AM J MED
JI Am. J. Med.
PD JUL
PY 2016
VL 129
IS 7
AR 753.e13
DI 10.1016/j.amjmed.2016.02.039
PG 10
WC Medicine, General & Internal
SC General & Internal Medicine
GA DO8WJ
UT WOS:000378065800049
PM 27036394
ER
PT J
AU Lichtveld, M
Kennedy, S
Krouse, RZ
Grimsley, F
El-Dahr, J
Bordelon, K
Sterling, Y
White, L
Barlow, N
DeGruy, S
Paul, D
Denham, S
Hayes, C
Sanders, M
Mvula, MM
Thornton, E
Chulada, P
Mitchell, H
Martin, WJ
Stephens, KU
Cohn, RD
AF Lichtveld, Maureen
Kennedy, Suzanne
Krouse, Rebecca Z.
Grimsley, Faye
El-Dahr, Jane
Bordelon, Keith
Sterling, Yvonne
White, LuAnn
Barlow, Natasha
DeGruy, Shannon
Paul, Dorothy
Denham, Stacey
Hayes, Claire
Sanders, Margaret
Mvula, Mosanda M.
Thornton, Eleanor
Chulada, Patricia
Mitchell, Herman
Martin, William J., II
Stephens, Kevin U.
Cohn, Richard D.
TI From Design to Dissemination: Implementing Community-Based Participatory
Research in Postdisaster Communities
SO AMERICAN JOURNAL OF PUBLIC HEALTH
LA English
DT Article
ID OFF ENVIRONMENTAL ASTHMA; KATRINA NEW-ORLEANS; LOUISIANA HEAL; CHILDREN;
EXPOSURES
AB Objectives. To review how disasters introduce unique challenges to conducting population-based research and community-based participatory research (CBPR).
Methods. From 2007-2009, we conducted the Head-off Environmental Asthma in Louisiana (HEAL) Study in the aftermath of Hurricane Katrina in a Gulf Coast community facing an unprecedented triple burden: Katrina's and other disasters' impact on the environment and health, historic health disparities, and persistent environmental health threats.
Results. The unique triple burden influenced every research component; still, most existing CBPR principles were applicable, even though full adherence was not always feasible and additional tailored principles govern postdisaster settings.
Conclusions. Even in the most challenging postdisaster conditions, CBPR can be successfully designed, implemented, and disseminated while adhering to scientific rigor.
C1 [Lichtveld, Maureen; Grimsley, Faye; White, LuAnn; Barlow, Natasha; DeGruy, Shannon; Paul, Dorothy] Tulane Univ, Sch Publ Hlth & Trop Med, New Orleans, LA USA.
[Kennedy, Suzanne; Krouse, Rebecca Z.; Mitchell, Herman] Rho Fed Syst Div Inc, Chapel Hill, NC USA.
[El-Dahr, Jane] Tulane Univ, Sch Med, Dept Pediat, New Orleans, LA 70112 USA.
[Bordelon, Keith; Cohn, Richard D.] Constella Grp LLC, Durham, NC USA.
[Sterling, Yvonne] Louisiana State Univ, Hlth Sci Ctr, Sch Nursing, New Orleans, LA USA.
[Denham, Stacey; Hayes, Claire; Sanders, Margaret; Mvula, Mosanda M.; Stephens, Kevin U.] New Orleans Hlth Dept, New Orleans, LA USA.
[Thornton, Eleanor] Visionary Consulting Partners LLC, Fairfax, VA USA.
[Chulada, Patricia; Martin, William J., II] NIEHS, NIH, Dept Hlth & Human Serv, POB 12233, Res Triangle Pk, NC 27709 USA.
RP Lichtveld, M (reprint author), 1440 Canal St,Suite 2100, New Orleans, LA 70112 USA.
EM mlichtve@tulane.edu
FU National Center of Minority Health and Health Disparities (NCMHD);
National Institute of Environmental Health Sciences (NIEHS), National
Institutes of Health (NIH) [NO1-ES-55553]; Merck Childhood Asthma
Network, Inc (MCAN); NIH; Foundation for the National Institutes of
Health; Louisiana Board of Regents RC/EEP
FX This project was funded by the National Center of Minority Health and
Health Disparities (NCMHD, now the NIMHD); the National Institute of
Environmental Health Sciences (NIEHS), National Institutes of Health
(NIH; contract NO1-ES-55553); and the Merck Childhood Asthma Network,
Inc (MCAN). Public-private funding provided by the NIH and MCAN was
managed under the auspices of the Foundation for the National Institutes
of Health. Other organizations that contributed include the National
Toxicology Program (NIEHS), the US Environmental Protection Agency
(Cincinnati, OH), and the de Laski Family Foundation. The Clinical and
Translational Research Center of Tulane and Louisiana State Universities
Schools of Medicine was supported in whole or in part by funds provided
through the Louisiana Board of Regents RC/EEP.
NR 22
TC 0
Z9 0
U1 2
U2 7
PU AMER PUBLIC HEALTH ASSOC INC
PI WASHINGTON
PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA
SN 0090-0036
EI 1541-0048
J9 AM J PUBLIC HEALTH
JI Am. J. Public Health
PD JUL
PY 2016
VL 106
IS 7
BP 1235
EP 1242
DI 10.2105/AJPH.2016.303169
PG 8
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA DO7CL
UT WOS:000377939700044
PM 27196662
ER
PT J
AU Assadipour, Y
Azoury, SC
Schaub, NN
Hong, Y
Eil, R
Inchauste, SM
Steinberg, SM
Venkatesan, AM
Libutti, SK
Hughes, MS
AF Assadipour, Yasmine
Azoury, Said C.
Schaub, Nicholas N.
Hong, Young
Eil, Robert
Inchauste, Suzanne M.
Steinberg, Seth M.
Venkatesan, Aradhana M.
Libutti, Steven K.
Hughes, Marybeth S.
TI Significance of preoperative radiographic pancreatic density in
predicting pancreatic fistula after surgery for pancreatic
neuroendocrine tumors
SO AMERICAN JOURNAL OF SURGERY
LA English
DT Article
DE Pancreatic fistula; Neuroendocrine tumors; Pancreaticoduo denectomy;
Pancreatic resection; Pancreatic enucleation
ID INTERNATIONAL STUDY-GROUP; RISK-FACTORS; PROPHYLACTIC OCTREOTIDE;
PANCREATICODUODENECTOMY; COMPLICATIONS; RESECTION; OUTCOMES
AB BACKGROUND: Postoperative pancreatic fistula remains the most severe and worrisome complication after surgery. Predictive preoperative assessment remains challenging. The authors examine the role of pancreatic computed tomography density in predicting postoperative pancreatic fistula after surgery for pancreatic neuroendocrine tumors.
METHODS: A single institutional retrospective review of pancreatic surgery for neuroendocrine tumors between 1998 and 2010 was conducted. Preoperative contrast-enhanced computed tomography scans were reviewed, with mean region of interest measurements of pancreatic parenchymal density obtained from 10-mm thick axial computed tomography images.
RESULTS: A total of 119 patients were identified: 59 with enucleations and 60 with resections. Decreased preoperative pancreatic density was significantly associated with an increased grade of postoperative pancreatic fistula (P < .01). Subgroup analyses revealed that decreased gland density was associated with increased grade of postoperative pancreatic fistula in the resection (P < .01) but not in the enucleation group (P = .34).
CONCLUSIONS: A significant association between postoperative pancreatic fistula grade and preoperative pancreatic computed tomography density is observed in patients undergoing resection for pancreatic neuroendocrine tumors. Published by Elsevier Inc.
C1 [Assadipour, Yasmine; Azoury, Said C.; Schaub, Nicholas N.; Hong, Young; Eil, Robert; Inchauste, Suzanne M.; Hughes, Marybeth S.] NCI, Surg Branch, Ctr Canc Res, Bldg 10, Bethesda, MD 20892 USA.
[Azoury, Said C.; Hughes, Marybeth S.] NCI, Thorac & Gastrointestinal Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Steinberg, Seth M.] NCI, Biostat & Data Management Sect, Ctr Canc Res, Bethesda, MD 20892 USA.
[Venkatesan, Aradhana M.] NIH, Radiol & Imaging Sci NIH Clin Ctr, Bldg 10, Bethesda, MD 20892 USA.
[Libutti, Steven K.] Montefiore Med Ctr, Albert Einstein Coll Med, Dept Surg, Bronx, NY 10467 USA.
RP Hughes, MS (reprint author), NCI, Surg Branch, Ctr Canc Res, Bldg 10, Bethesda, MD 20892 USA.; Hughes, MS (reprint author), NCI, Thorac & Gastrointestinal Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
EM hughesm@mail.nih.gov
FU Intramural Program of the National Cancer Institute
FX All funding is provided by the Intramural Program of the National Cancer
Institute; this did not create a conflict of interest.
NR 23
TC 0
Z9 0
U1 0
U2 1
PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC
PI BRIDGEWATER
PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA
SN 0002-9610
EI 1879-1883
J9 AM J SURG
JI Am. J. Surg.
PD JUL
PY 2016
VL 212
IS 1
BP 40
EP 46
DI 10.1016/j.amjsurg.2015.07.031
PG 7
WC Surgery
SC Surgery
GA DO8VM
UT WOS:000378063100006
PM 26782807
ER
PT J
AU Wilson, CJ
Mitchelson, AJ
Tzeng, TH
El-Othmani, MM
Saleh, J
Vasdev, S
LaMontagne, HJ
Saleh, KJ
AF Wilson, Craig J.
Mitchelson, Andrew J.
Tzeng, Tony H.
El-Othmani, Mouhanad M.
Saleh, Jasmine
Vasdev, Sonia
LaMontagne, Hillary J.
Saleh, Khaled J.
TI Caring for the surgically anxious patient: a review of the interventions
and a guide to optimizing surgical outcomes
SO AMERICAN JOURNAL OF SURGERY
LA English
DT Review
DE Preoperative anxiety; Perioperative anxiety; Psychiatric anxiety survey;
Patient education; Surgical anxiety intervention; Preoperative
anxiolytics
ID AMSTERDAM PREOPERATIVE ANXIETY; RANDOMIZED CONTROLLED-TRIAL; TOTAL
HIP-REPLACEMENT; ARTERY-BYPASS GRAFT; SURGERY PATIENTS; REDUCE ANXIETY;
CLINICAL-TRIAL; CARDIAC-CATHETERIZATION; PERIOPERATIVE ANXIETY;
POSTOPERATIVE ANXIETY
AB BACKGROUND: Preoperative surgical anxiety is an unpleasant and common reaction exhibited by patients who are scheduled for surgical procedures. Beyond emotional effects on the patient, it can also have negative repercussions on the surgery including longer hospital stays and poorer outcomes. Given the widespread impacts of preoperative anxiety, it is critical for surgeons to gain a better understanding of how to identify and reduce surgical anxiety in their patients.
DATA SOURCES: This study used the PubMed database to review the current literature to evaluate screening tools and interventions for surgically anxious patients.
CONCLUSIONS: Psychiatric anxiety surveys are currently the most appropriate form of assessment for surgical anxiety. Patient education is important for preventing and reducing anxiety levels in patients. Both nonpharmacological and pharmacological interventions have been shown to be effective in reducing patient anxiety and treatment should be based on patient preference, resources available, and the surgeon's experience. (C) 2015 Elsevier Inc. All rights reserved.
C1 [Wilson, Craig J.; Mitchelson, Andrew J.; Tzeng, Tony H.; El-Othmani, Mouhanad M.; Vasdev, Sonia; Saleh, Khaled J.] So Illinois Univ, Sch Med, Dept Surg, Div Orthopaed & Rehabil, Springfield, IL 62794 USA.
[Saleh, Jasmine] Natl Inst Deafness & Other Communicable Disorders, NIH, Bethesda, MD USA.
[LaMontagne, Hillary J.] So Illinois Univ, Sch Med, Dept Psychiat, Springfield, IL USA.
RP El-Othmani, MM (reprint author), So Illinois Univ, Sch Med, Dept Surg, Div Orthopaed & Rehabil, Springfield, IL 62794 USA.
EM mohannad.othmani@gmail.com
OI Mitchelson, Andrew/0000-0001-5348-6495; El-Othmani,
Mouhanad/0000-0001-7211-4072
NR 110
TC 0
Z9 0
U1 1
U2 4
PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC
PI BRIDGEWATER
PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA
SN 0002-9610
EI 1879-1883
J9 AM J SURG
JI Am. J. Surg.
PD JUL
PY 2016
VL 212
IS 1
BP 151
EP 159
DI 10.1016/j.amjsurg.2015.03.023
PG 9
WC Surgery
SC Surgery
GA DO8VM
UT WOS:000378063100021
PM 26138522
ER
PT J
AU Gaskell, J
Blanchette, RA
Stewart, PE
BonDurant, SS
Adams, M
Sabat, G
Kersten, P
Cullen, D
AF Gaskell, Jill
Blanchette, Robert A.
Stewart, Philip E.
BonDurant, Sandra Splinter
Adams, Marie
Sabat, Grzegorz
Kersten, Phil
Cullen, Dan
TI Transcriptome and Secretome Analyses of the Wood Decay Fungus Wolfiporia
cocos Support Alternative Mechanisms of Lignocellulose Conversion
SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY
LA English
DT Article
ID BASIDIOMYCETE PHANEROCHAETE-CHRYSOSPORIUM; BROWN-ROT; POSTIA-PLACENTA;
GLOEOPHYLLUM-TRABEUM; DEGRADATION; CELLULOSE; DATABASE; GENOMES;
OXIDASE; IRON
AB Certain wood decay basidiomycetes, collectively referred to as brown rot fungi, rapidly depolymerize cellulose while leaving behind the bulk of cell wall lignin as a modified residue. The mechanism(s) employed is unclear, but considerable evidence implicates the involvement of diffusible oxidants generated via Fenton-like chemistry. Toward a better understanding of this process, we have examined the transcriptome and secretome of Wolfiporia cocos when cultivated on media containing glucose, purified crystalline cellulose, aspen (Populus grandidentata), or lodgepole pine (Pinus contorta) as the sole carbon source. Compared to the results obtained with glucose, 30, 183, and 207 genes exhibited 4-fold increases in transcript levels in cellulose, aspen, and lodgepole pine, respectively. Mass spectrometry identified peptides corresponding to 64 glycoside hydrolase (GH) proteins, and of these, 17 corresponded to transcripts upregulated on one or both woody substrates. Most of these genes were broadly categorized as hemicellulases or chitinases. Consistent with an important role for hydroxyl radical in cellulose depolymerization, high transcript levels and upregulation were observed for genes involved in iron homeostasis, iron reduction, and extracellular peroxide generation. These patterns of regulation differ markedly from those of the closely related brown rot fungus Postia placenta and expand the number of enzymes potentially involved in the oxidative depolymerization of cellulose.
C1 [Gaskell, Jill; Kersten, Phil; Cullen, Dan] USDA, Forest Prod Lab, Madison, WI 53705 USA.
[Blanchette, Robert A.] Univ Minnesota, Dept Plant Pathol, St Paul, MN USA.
[Stewart, Philip E.] NIAID, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA.
[BonDurant, Sandra Splinter; Adams, Marie; Sabat, Grzegorz] Univ Wisconsin, Madison Biotechnol Ctr, Madison, WI USA.
RP Cullen, D (reprint author), USDA, Forest Prod Lab, Madison, WI 53705 USA.
EM dcullen@wisc.edu
FU National Research Initiative of the U.S. Department of Agriculture
Cooperative State, Research Education and Extension Service grant [2007
35504 18257]
FX This work was supported in part by the National Research Initiative of
the U.S. Department of Agriculture Cooperative State, Research Education
and Extension Service grant 2007 35504 18257, to D.C. and R.A.B.
NR 47
TC 1
Z9 1
U1 8
U2 17
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0099-2240
EI 1098-5336
J9 APPL ENVIRON MICROB
JI Appl. Environ. Microbiol.
PD JUL
PY 2016
VL 82
IS 13
BP 3979
EP 3987
DI 10.1128/AEM.00639-16
PG 9
WC Biotechnology & Applied Microbiology; Microbiology
SC Biotechnology & Applied Microbiology; Microbiology
GA DO8QP
UT WOS:000378048800030
PM 27107121
ER
PT J
AU Schiller, CE
Johnson, SL
Abate, AC
Schmidt, PJ
Rubinow, DR
AF Schiller, Crystal Edler
Johnson, Sarah L.
Abate, Anna C.
Schmidt, Peter J.
Rubinow, David R.
TI Reproductive Steroid Regulation of Mood and Behavior
SO COMPREHENSIVE PHYSIOLOGY
LA English
DT Article
ID PREMENSTRUAL DYSPHORIC DISORDER; MAJOR DEPRESSIVE DISORDER; DEFAULT-MODE
NETWORK; STRESS-INDUCED ANHEDONIA; ESTROGEN-RECEPTOR-ALPHA; FRONTAL EEG
ASYMMETRY; MENSTRUAL-CYCLE PHASE; DORSOLATERAL PREFRONTAL CORTEX;
POSTMENOPAUSAL HORMONE-THERAPY; STATE FUNCTIONAL CONNECTIVITY
AB In this article, we examine evidence supporting the role of reproductive steroids in the regulation of mood and behavior in women and the nature of that role. In the first half of the article, we review evidence for the following: (i) the reproductive system is designed to regulate behavior; (ii) from the subcellular to cellular to circuit to behavior, reproductive steroids are powerful neuroregulators; (iii) affective disorders are disorders of behavioral state; and (iv) reproductive steroids affect virtually every system implicated in the pathophysiology of depression. In the second half of the article, we discuss the diagnosis of the three reproductive endocrine-related mood disorders (premenstrual dysphoric disorder, postpartum depression, and perimenopausal depression) and present evidence supporting the relevance of reproductive steroids to these conditions. Existing evidence suggests that changes in reproductive steroid levels during specific reproductive states (i.e., the premenstrual phase of the menstrual cycle, pregnancy, parturition, and the menopause transition) trigger affective dysregulation in susceptible women, thus suggesting the etiopathogenic relevance of these hormonal changes in reproductive mood disorders. Understanding the source of individual susceptibility is critical to both preventing the onset of illness and developing novel, individualized treatments for reproductive-related affective dysregulation. (C) 2016 American Physiological Society.
C1 [Schiller, Crystal Edler; Johnson, Sarah L.; Abate, Anna C.; Rubinow, David R.] Univ N Carolina, Dept Psychiat, Chapel Hill, NC 27514 USA.
[Schmidt, Peter J.] NIMH, Sect Behav Endocrinol, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
RP Rubinow, DR (reprint author), Univ N Carolina, Dept Psychiat, Chapel Hill, NC 27514 USA.
EM david_rubinow@med.unc.edu
NR 366
TC 1
Z9 1
U1 16
U2 21
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 2040-4603
J9 COMPR PHYSIOL
JI Compr. Physiol.
PD JUL
PY 2016
VL 6
IS 3
BP 1135
EP 1160
DI 10.1002/cphy.c150014
PG 26
WC Physiology
SC Physiology
GA DP1EB
UT WOS:000378232200001
PM 27347888
ER
PT J
AU Eriksson, O
Laughlin, M
Brom, M
Nuutila, P
Roden, M
Hwa, A
Bonadonna, R
Gotthardt, M
AF Eriksson, Olof
Laughlin, Maren
Brom, Maarten
Nuutila, Pirjo
Roden, Michael
Hwa, Albert
Bonadonna, Riccardo
Gotthardt, Martin
TI In vivo imaging of beta cells with radiotracers: state of the art,
prospects and recommendations for development and use
SO DIABETOLOGIA
LA English
DT Review
DE Beta cell; Beta cell imaging; Diabetes; Exendin; Islet imaging; Islets
of Langerhans; PET; Review; SPECT
ID POSITRON-EMISSION-TOMOGRAPHY; HUMAN PANCREAS; RECEPTOR EXPRESSION;
PEPTIDE-1 RECEPTOR; ENDOCRINE PANCREAS; EUROPEAN SUBJECTS; VMAT2
EXPRESSION; GLP-1 RECEPTOR; ADULT PATIENTS; RAT PANCREAS
AB Radiotracer imaging is characterised by high in vivo sensitivity, with a detection limit in the lower picomolar range. Therefore, radiotracers represent a valuable tool for imaging pancreatic beta cells. High demands are made of radiotracers for in vivo imaging of beta cells. Beta cells represent only a small fraction of the volume of the pancreas (usually 1-3%) and are scattered in the tiny islets of Langerhans throughout the organ. In order to be able to measure a beta cell-specific signal, one has to rely on highly specific tracer molecules because current in vivo imaging technologies do not allow the resolution of single islets in humans non-invasively. Currently, a considerable amount of preclinical data are available for several radiotracers and three are under clinical evaluation. We summarise the current status of the evaluation of these tracer molecules and put forward recommendations for their further evaluation.
C1 [Eriksson, Olof] Uppsala Univ, Dept Med Chem, Preclin PET Platform, Dag Hammarskjolds Vag 14C,3tr, SE-75183 Uppsala, Sweden.
[Eriksson, Olof; Nuutila, Pirjo] Univ Turku, Turku PET Ctr, Turku, Finland.
[Eriksson, Olof] Abo Akad Univ, Dept Biosci, Turku, Finland.
[Laughlin, Maren] NIDDK, NIH, Bethesda, MD 20892 USA.
[Brom, Maarten; Gotthardt, Martin] Radboud Univ Nijmegen, Dept Radiol & Nucl Med, Med Ctr, POB 9101, NL-6500 HB Nijmegen, Netherlands.
[Roden, Michael] Univ Dusseldorf, Fac Med, Dept Endocrinol & Diabetol, Dusseldorf, Germany.
[Roden, Michael] Univ Dusseldorf, Leibniz Ctr Diabet Res, German Diabet Ctr, Inst Clin Diabetol, Dusseldorf, Germany.
[Hwa, Albert] JDRF, Discovery Res, New York, NY USA.
[Bonadonna, Riccardo] Univ Parma, Dept Clin & Expt Med, Div Endocrinol, I-43100 Parma, Italy.
[Bonadonna, Riccardo] AOU Parma, Parma, Italy.
RP Eriksson, O (reprint author), Uppsala Univ, Dept Med Chem, Preclin PET Platform, Dag Hammarskjolds Vag 14C,3tr, SE-75183 Uppsala, Sweden.; Eriksson, O (reprint author), Univ Turku, Turku PET Ctr, Turku, Finland.; Eriksson, O (reprint author), Abo Akad Univ, Dept Biosci, Turku, Finland.; Gotthardt, M (reprint author), Radboud Univ Nijmegen, Dept Radiol & Nucl Med, Med Ctr, POB 9101, NL-6500 HB Nijmegen, Netherlands.
EM olof.eriksson@pet.medchem.uu.se; martin.gotthardt@radboudumc.nl
RI Brom, Maarten/J-1953-2014;
OI Brom, Maarten/0000-0001-5755-1477; Bonadonna,
Riccardo/0000-0002-9809-1005
NR 57
TC 2
Z9 2
U1 3
U2 10
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0012-186X
EI 1432-0428
J9 DIABETOLOGIA
JI Diabetologia
PD JUL
PY 2016
VL 59
IS 7
BP 1340
EP 1349
DI 10.1007/s00125-016-3959-7
PG 10
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA DO8QH
UT WOS:000378047800002
PM 27094935
ER
PT J
AU Zhang, CL
Rawal, S
Chong, YS
AF Zhang, Cuilin
Rawal, Shristi
Chong, Yap Seng
TI Risk factors for gestational diabetes: is prevention possible?
SO DIABETOLOGIA
LA English
DT Review
DE Diet; Gestational diabetes; Intervention; Lifestyle; Prevention; Review;
Risk factors
ID RANDOMIZED CONTROLLED-TRIAL; OBESE PREGNANT-WOMEN; PHYSICAL-ACTIVITY
INTERVENTIONS; MELLITUS PROSPECTIVE COHORT; HEALTHY LIFE-STYLE;
WEIGHT-GAIN; DIETARY PATTERNS; EXERCISE; METAANALYSIS; ASSOCIATION
AB Gestational diabetes mellitus (GDM), a common pregnancy complication, continues to be a significant public health and clinical problem. It carries significant short-term and long-term adverse health outcomes for both mother and offspring, which reinforces the significance of understanding risk factors, in particular modifiable factors, for GDM and of preventing the condition. Research in the past decade from observational studies has identified a few diet and lifestyle factors that are associated with GDM risk and demonstrated that time frames both before and during pregnancy may be relevant to the development of GDM. Findings from intervention studies on the effect of diet and lifestyle on the prevention of GDM have been largely controversial and inconsistent. Variations in study population, types of intervention, timing and duration of intervention and diagnostic criteria for GDM may all at least partly account for the large heterogeneity in the findings from these intervention studies. This review provides an overview of emerging diet, lifestyle, and other factors that may help to prevent GDM, and the challenges associated with prevention. It also discusses major methodological concerns about the available epidemiological studies on GDM risk factors. Findings from both observational and intervention studies are discussed. This review summarises a presentation given at the 'Gestational diabetes: what's up?' symposium at the 2015 annual meeting of the EASD. It is accompanied by two other reviews on topics from this symposium (by Peter Damm and Colleagues, DOI: 10.1007/s00125-016-3985-5, and by Marja Vaarasmaki, DOI: 10.1007/s00125-016-3976-6<) and an overview by the Session Chair, Kerstin Berntorp (DOI: 10.1007/s00125-016-3975-7).
C1 [Zhang, Cuilin; Rawal, Shristi] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Intramural Populat Hlth Res, NIH, 6100 Execut Blvd, Rockville, MD 20852 USA.
[Chong, Yap Seng] Agcy Sci Technol & Res, Singapore Inst Clin Sci, Singapore, Singapore.
[Chong, Yap Seng] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Obstet & Gynaecol, Singapore 117595, Singapore.
RP Zhang, CL (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Intramural Populat Hlth Res, NIH, 6100 Execut Blvd, Rockville, MD 20852 USA.
EM zhangcu@mail.nih.gov
FU Intramural Research Program of the Eunice Kennedy Shriver National
Institute of Child Health & Human Development, National Institutes of
Health
FX CZ and SR are supported by the Intramural Research Program of the Eunice
Kennedy Shriver National Institute of Child Health & Human Development,
National Institutes of Health.
NR 49
TC 1
Z9 1
U1 18
U2 23
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0012-186X
EI 1432-0428
J9 DIABETOLOGIA
JI Diabetologia
PD JUL
PY 2016
VL 59
IS 7
BP 1385
EP 1390
DI 10.1007/s00125-016-3979-3
PG 6
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA DO8QH
UT WOS:000378047800010
PM 27165093
ER
PT J
AU Xing, CH
Huang, J
Hsu, YH
DeStefano, AL
Heard-Costa, NL
Wolf, PA
Seshadri, S
Kiel, DP
Cupples, LA
Dupuis, J
AF Xing, Chuanhua
Huang, Jie
Hsu, Yi-Hsiang
DeStefano, Anita L.
Heard-Costa, Nancy L.
Wolf, Philip A.
Seshadri, Sudha
Kiel, Douglas P.
Cupples, L. Adrienne
Dupuis, Josee
TI Evaluation of power of the Illumina HumanOmni5M-4v1 BeadChip to detect
risk variants for human complex diseases
SO EUROPEAN JOURNAL OF HUMAN GENETICS
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; LINKAGE DISEQUILIBRIUM; GENOTYPE IMPUTATION;
COVERAGE; EXTENT
AB Although emerging sequencing technologies can characterize all genetic variants, the cost is still high. Illumina released the HumanOmni5M-4v1 (Omni5) genotype array with similar to 4.3M assayed SNPs, a much denser array compared with other available arrays. The Omni5 balances both cost and array density. In this article, we illustrate the power of Omni5 to detect genetic associations. The Omni5 includes variants with a wide range of minor allele frequencies down to <1%. The theoretical power calculation examples indicate the increased power of the Omni5 array compared with other arrays with lower density when evaluating associations with some known loci, although there are exceptions. We further evaluate the genetic associations between known loci and several quantitative traits in the Framingham Heart Study: femoral neck bone mineral density, lumbar spine bone mineral density and hippocampal volume. Finally, we search genome wide for novel associations using the Omni5 genotypes. We compare our association results from Affymetrix 500K+MIPS 50K arrays and two imputed data sets: (1) HapMap Phase II and (2) 1000 Genomes reference panel. We observed increased evidence for genotype-phenotype associations with smaller P-values for selected known loci using the Omni5 genotypes. With limited sample sizes, we identify novel variants with genome-wide significant P-values. Our observations support the notion that dense genotyping using the Omni5 can be powerful in detecting novel associated variants. Comparison with imputed data with higher density also suggests that imputation helps but cannot replace genotyping, especially when imputation quality is low.
C1 [Xing, Chuanhua; DeStefano, Anita L.; Cupples, L. Adrienne; Dupuis, Josee] Boston Univ, Dept Biostat, Sch Publ Hlth, Third Floor,801 Massachusetts Ave, Boston, MA 02118 USA.
[Huang, Jie] Wellcome Trust Sanger Inst, Dept Human Genet, Hinxton, England.
[Hsu, Yi-Hsiang; Kiel, Douglas P.] Hebrew SeniorLife, Inst Aging Res, Boston, MA USA.
[Hsu, Yi-Hsiang; Kiel, Douglas P.] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA.
[Hsu, Yi-Hsiang; Kiel, Douglas P.] Harvard Univ, Sch Med, Boston, MA USA.
[Hsu, Yi-Hsiang] Harvard Univ, Sch Publ Hlth, Mol & Integrat Physiol Sci Program, 665 Huntington Ave, Boston, MA 02115 USA.
[DeStefano, Anita L.; Heard-Costa, Nancy L.; Wolf, Philip A.; Seshadri, Sudha] Boston Univ, Sch Med, Dept Neurol, Third Floor,801 Massachusetts Ave, Boston, MA 02118 USA.
[DeStefano, Anita L.; Heard-Costa, Nancy L.; Wolf, Philip A.; Seshadri, Sudha; Cupples, L. Adrienne; Dupuis, Josee] NHLBI, Framingham Heart Study, Framingham, MA USA.
RP Dupuis, J (reprint author), Boston Univ, Dept Biostat, Sch Publ Hlth, Third Floor,801 Massachusetts Ave, Boston, MA 02118 USA.; Xing, CH (reprint author), Boston Univ, Dept Biostat, POB 152, Gaithersburg, MD 20884 USA.
EM chuanhua.xing@gmail.com; dupuis@bu.edu
OI Kiel, Douglas/0000-0001-8474-0310
FU National Heart, Lung and Blood Institute's Framingham Heart Study
[N01-HC-25195]; Affymetrix, Inc [N02-HL-6-4278]; Robert Dawson Evans
Endowment of the Department of Medicine at Boston University School of
Medicine and Boston Medical Center; NINDS [NS17950]; NHLBI [HL102419,
HL096917]; NIA [AG08122, AG16495, AG033193]; NIAMS [R01 AR/AG 41398]
FX We would like to acknowledge the work of Larry Atwood for his early
efforts in connecting Illumina and Boston University. Genotyping of
similar to 4.3M SNPs was conducted in subset of 2500 Framingham
Offspring Cohort participants using the Illumina HumanOmni5M-4v1 array
designed to target variation down to 1% minor allele frequency. This
genotyping was produced at no charge by Illumina under an agreement
between Illumina and Boston University. This work was supported by the
National Heart, Lung and Blood Institute's Framingham Heart Study
(Contract no. N01-HC-25195) and its contract with Affymetrix, Inc for
genotyping services (Contract no. N02-HL-6-4278). A portion of this
research utilized the Linux Cluster for Genetic Analysis (LinGA-II)
funded by the Robert Dawson Evans Endowment of the Department of
Medicine at Boston University School of Medicine and Boston Medical
Center. This study was also supported by grants from the NINDS
(NS17950), the NHLBI (HL102419, HL096917) and the NIA (AG08122, AG16495,
AG033193). Additional support for the skeletal phenotypes was obtained
from NIAMS (R01 AR/AG 41398).
NR 16
TC 0
Z9 0
U1 1
U2 1
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1018-4813
EI 1476-5438
J9 EUR J HUM GENET
JI Eur. J. Hum. Genet.
PD JUL
PY 2016
VL 24
IS 7
BP 1029
EP 1034
DI 10.1038/ejhg.2015.244
PG 6
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA DO9IA
UT WOS:000378098000014
PM 26577045
ER
PT J
AU Paredes, A
Saenz, P
Marzal, MW
Orrego, MA
Castillo, Y
Rivera, A
Mahanty, S
Guerra-Giraldez, C
Garcia, HH
Nash, TE
AF Paredes, Adriana
Saenz, Patricia
Marzal, Miguel W.
Orrego, Miguel A.
Castillo, Yesenia
Rivera, Andrea
Mahanty, Siddhartha
Guerra-Giraldez, Cristina
Garcia, Hector H.
Nash, Theodore E.
CA Cysticercosis Working Grp Peru
TI Anti-Taenia solium monoclonal antibodies for the detection of parasite
antigens in body fluids from patients with neurocysticercosis
SO EXPERIMENTAL PARASITOLOGY
LA English
DT Article
DE Taenia solium; Monoclonal antibodies; Capture ELISA; Neurocysticercosis;
Diagnosis
ID HP10 ANTIGEN; FOLLOW-UP; DIAGNOSIS; CYSTICERCOSIS; SERUM; ELISA
AB Neurocysticercosis (NCC), an infection of the brain by Taenia solium (Ts) cysts, is the most common cause of adult-onset epilepsy in developing countries. Serological testing consists primarily of varying methods to detect antibodies in body fluids and more recently antigen (Ag) detection assays to identify individuals or animals with viable parasites. Antigen assays currently in use employ monoclonal antibodies (mAbs) raised against T. saginata, which have known cross reactivity to animal cestodes but are highly specific in human samples. We produced, characterized and tested 21 mAbs raised against T. solium whole cyst antigens, vesicular fluid or excretory secretory products. Reactivity of the TsmAbs against specific cyst structures was determined using immunofluorescence and immunohistochemistry on histological sections of Ts muscle cysts. Four TsmAbs reacted to vesicular space alone, 9 to the neck and cyst wall, one to the neck and vesicular space and 7 to the neck, cyst wall and vesicular space. An in-house ELISA assay to detect circulating Ts antigen, using the TsmAbs as capture antibodies and a rabbit polyclonal anti-Ts whole cyst antibody as a detector antibody demonstrated that eight of the 21 TsmAbs detected antigens in known NCC-positive human sera and three of these also in urine samples. Reactivity was expressed as normalized ratios of optical densities (OD positive control/OD negative control). Three TsmAbs had ratios >10 and five between 2 and 10. The TsmAbs have potential utility for the diagnosis and post-treatment monitoring of patients with viable NCC infections. (C) 2016 Elsevier Inc. All rights reserved.
C1 [Paredes, Adriana; Saenz, Patricia; Marzal, Miguel W.; Orrego, Miguel A.; Rivera, Andrea; Mahanty, Siddhartha; Guerra-Giraldez, Cristina; Nash, Theodore E.] Univ Peruana Cayetano Heredia, Fac Ciencias & Filosofia, Lab Inmunopatol Neurocisticercosis, Lima, Peru.
[Castillo, Yesenia; Garcia, Hector H.] Univ Peruana Cayetano Heredia, Fac Ciencias & Filosofia, Lab Inmunol Parasitaria, Lima, Peru.
[Mahanty, Siddhartha; Nash, Theodore E.] NIAID, Parasit Dis Lab, NIH, Bethesda, MD USA.
[Guerra-Giraldez, Cristina; Garcia, Hector H.] Univ Peruana Cayetano Heredia, Fac Ciencias & Filosofia, Dept Ciencias Celulares & Mol, Lima, Peru.
[Garcia, Hector H.] Inst Nacl Ciencias Neurol, Unidad Cisticercosis, Lima, Peru.
RP Guerra-Giraldez, C (reprint author), Univ Peruana Cayetano Heredia, Fac Ciencias & Filosofia, Dept Ciencias Celulares & Mol, Lima, Peru.
EM cristina.guerra@upch.pe
OI Guerra-Giraldez, Cristina/0000-0002-9287-9838; Mahanty,
Siddhartha/0000-0003-1068-0524
FU Innovate Peru [FINCyT-IA-231-2013]; NIH/FIC Training grant [TW001140];
National Institutes of Allergy and Infectious Diseases
FX This work was supported partially by Innovate Peru, project
FINCyT-IA-231-2013, by NIH/FIC Training grant TW001140, and by an
intramural research program of the National Institutes of Allergy and
Infectious Diseases.
NR 20
TC 1
Z9 1
U1 3
U2 7
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0014-4894
EI 1090-2449
J9 EXP PARASITOL
JI Exp. Parasitol.
PD JUL
PY 2016
VL 166
BP 37
EP 43
DI 10.1016/j.exppara.2016.03.025
PG 7
WC Parasitology
SC Parasitology
GA DP4JK
UT WOS:000378462000006
PM 27018063
ER
PT J
AU Verma, M
AF Verma, Mukesh
TI Genome-wide association studies and epigenome-wide association studies
go together in cancer control
SO FUTURE ONCOLOGY
LA English
DT Review
DE biomarkers; cancer; epidemiology; epigenetics; genomics; omics
technologies; outcome; personalized medicine; pharmacogenomics
ID SQUAMOUS-CELL CARCINOMA; DNA METHYLATION ANALYSIS; HUMAN-PAPILLOMAVIRUS
16; COPY NUMBER VARIATION; COLORECTAL-CANCER; BREAST-CANCER;
PROSTATE-CANCER; LUNG-CANCER; PANCREATIC-CANCER; SUSCEPTIBILITY LOCI
AB Completion of the human genome a decade ago laid the foundation for: using genetic information in assessing risk to identify individuals and populations that are likely to develop cancer, and designing treatments based on a person's genetic profiling ( precision medicine). Genome-wide association studies (GWAS) completed during the past few years have identified risk-associated single nucleotide polymorphisms that can be used as screening tools in epidemiologic studies of a variety of tumor types. This led to the conduct of epigenome-wide association studies (EWAS). This article discusses the current status, challenges and research opportunities in GWAS and EWAS. Information gained from GWAS and EWAS has potential applications in cancer control and treatment.
C1 [Verma, Mukesh] NCI, Methods & Technol Branch, Epidemiol & Genom Res Program, Div Canc Control & Populat Sci,NIH, 9609 Med Ctr Dr,Suite 4E102, Rockville, MD 20850 USA.
RP Verma, M (reprint author), NCI, Methods & Technol Branch, Epidemiol & Genom Res Program, Div Canc Control & Populat Sci,NIH, 9609 Med Ctr Dr,Suite 4E102, Rockville, MD 20850 USA.
EM vermam@mail.nih.gov
NR 149
TC 0
Z9 0
U1 11
U2 19
PU FUTURE MEDICINE LTD
PI LONDON
PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3
1QB, ENGLAND
SN 1479-6694
EI 1744-8301
J9 FUTURE ONCOL
JI Future Oncol.
PD JUL
PY 2016
VL 12
IS 13
BP 1645
EP 1664
DI 10.2217/fon-2015-0035
PG 20
WC Oncology
SC Oncology
GA DP3RS
UT WOS:000378413200011
PM 27079684
ER
PT J
AU Sei, Y
Feng, JY
Zhao, XL
Forbes, J
Tang, D
Nagashima, K
Hanson, J
Quezado, MM
Hughes, MS
Wank, SA
AF Sei, Yoshitatsu
Feng, Jianying
Zhao, Xilin
Forbes, Joanne
Tang, Derek
Nagashima, Kunio
Hanson, Jeffrey
Quezado, Martha M.
Hughes, Marybeth S.
Wank, Stephen A.
TI Polyclonal Crypt Genesis and Development of Familial Small Intestinal
Neuroendocrine Tumors
SO GASTROENTEROLOGY
LA English
DT Article
DE Small Intestine; Cancer; Malignancy; Gene Expression
ID MITOCHONDRIAL-DNA MUTATIONS; STEM-CELL POPULATIONS; ILEAL CARCINOIDS;
PROGENITOR CELLS; IN-VIVO; LGR5; MARKER; TUMORIGENESIS; ORIGIN; CANCER
AB BACKGROUND & AIMS: Small intestinal neuroendocrine tumors (SI-NETs) are serotonin-secreting well-differentiated neuroendocrine tumors believed to originate from entero-chromaffin (EC) cells. Intestinal stem cell (ISC) are believed to contribute to the formation of SI-NETs, although little is known about tumor formation or development. We investigated the relationship between EC cells, ISCs, and SI-NETs. METHODS: We analyzed jejuno-ileal tissue specimens from 14 patients with familial SI-NETs enrolled in the Natural History of Familial Carcinoid Tumor study at the National Institutes of Health from January 2009 to December 2014. Frozen and paraffin-embedded tumor tissues of different stages and isolated crypts were analyzed by in situ hybridization and immunohistochemistry. Tumor clonality was assessed by analyses of mitochondrial DNA. RESULTS: We identified multifocal aberrant crypt-containing endocrine cell clusters (ACECs) that contain crypt EC cell microtumors in patients with familial SI-NETs. RNA in situ hybridization revealed expression of the EC cell and reserve stem cell genes TPH1, BMI1, HOPX, and LGR5(low), in the ACECs and more advanced extraepithelial tumor nests. This expression pattern resembled that of reserve EC cells that express reserve ISC genes; most reside at the +4 position in normal crypts. The presence of multifocal ACECs from separate tumors and in the macroscopic tumor-free mucosa indicated widespread, independent, multifocal tumorigenesis. Analyses of mitochondrial DNA confirmed the independent origin of the ACECs. CONCLUSIONS: Familial SI-NETs originate from a subset of EC cells (reserve EC cells that express reserve ISC genes) via multifocal and polyclonal processes. Increasing our understanding of the role of these reserve EC cells in the genesis of multifocal SI-NETs could improve diagnostic and therapeutic strategies for this otherwise intractable disease.
C1 [Sei, Yoshitatsu; Feng, Jianying; Zhao, Xilin; Forbes, Joanne; Tang, Derek; Wank, Stephen A.] NIDDKD, Digest Dis Branch, NIH, 10 Ctr Dr,Bldg 10,Room 9C-101,MSC1804, Bethesda, MD 20892 USA.
[Nagashima, Kunio] Frederick Natl Lab Canc Res, Electron Microscopy Lab, Frederick, MD USA.
[Hanson, Jeffrey; Quezado, Martha M.] NCI, Pathol Lab, NIH, Bldg 10, Bethesda, MD 20892 USA.
[Hughes, Marybeth S.] NCI, Surg Branch, NIH, Bldg 10, Bethesda, MD 20892 USA.
RP Wank, SA (reprint author), NIDDKD, Digest Dis Branch, 10 Ctr Dr,Bldg 10,Room 9C-101,MSC1804, Bethesda, MD 20892 USA.
EM stevew@mail.nih.gov
OI Tang, Derek/0000-0002-9419-1869
FU National Institute of Diabetes, Digestive and Kidney Diseases; Clinical
Research Center; Frederick National Laboratory for Cancer Research;
National Cancer Institute, National Institutes of Health
FX This work was supported by the Intramural Research Programs of the
National Institute of Diabetes, Digestive and Kidney Diseases, Clinical
Research Center, Frederick National Laboratory for Cancer Research and
National Cancer Institute, National Institutes of Health.
NR 35
TC 2
Z9 2
U1 6
U2 6
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0016-5085
EI 1528-0012
J9 GASTROENTEROLOGY
JI Gastroenterology
PD JUL
PY 2016
VL 151
IS 1
BP 140
EP 151
DI 10.1053/j.gastro.2016.03.007
PG 12
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA DP5QD
UT WOS:000378551400030
PM 27003604
ER
PT J
AU Wong, RP
Tinsley, EA
Waclawiw, MA
Krull, HK
Lathrop, DA
AF Wong, Renee P.
Tinsley, Emily A.
Waclawiw, Myron A.
Krull, Holly K.
Lathrop, David A.
TI National, Heart, Lung, and Blood Institute support of cardiac arrhythmia
research
SO HEART RHYTHM
LA English
DT Editorial Material
C1 [Wong, Renee P.; Tinsley, Emily A.; Waclawiw, Myron A.; Krull, Holly K.; Lathrop, David A.] NHLBI, Heart Failure & Arrhythmias Branch, Adult & Pediat Cardiac Res Program, Div Cardiovasc Sci,NIH, Bldg 10, Bethesda, MD 20892 USA.
RP Lathrop, DA (reprint author), NHLBI, Div Cardiovasc Sci, 6701 Rockledge Dr,Room 8170, Bethesda, MD 20892 USA.
EM lathropd@nhlbi.nih.gov
NR 4
TC 0
Z9 0
U1 1
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1547-5271
EI 1556-3871
J9 HEART RHYTHM
JI Heart Rhythm
PD JUL
PY 2016
VL 13
IS 7
BP 1570
EP 1572
DI 10.1016/j.hrthm.2016.03.001
PG 3
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA DO9FK
UT WOS:000378090000030
PM 26945850
ER
PT J
AU Choi, H
Chung, H
Muntaner, C
Lee, M
Kim, Y
Barry, CE
Cho, SN
AF Choi, H.
Chung, H.
Muntaner, C.
Lee, M.
Kim, Y.
Barry, C. E., III
Cho, S-N.
TI The impact of social conditions on patient adherence to pulmonary
tuberculosis treatment
SO INTERNATIONAL JOURNAL OF TUBERCULOSIS AND LUNG DISEASE
LA English
DT Article
DE TB; socio-economic position; adherence; loss to follow-up; infectious
epidemiology
ID SOUTH-AFRICA; ANTITUBERCULOSIS TREATMENT; DEFAULT; INTERVENTIONS;
NONADHERENCE; PREDICTORS; MORTALITY; EDUCATION; BARRIERS; RISK
AB SETTING: Tuberculosis (TB) remains one of the main concerns in global health. One of the main threats to treatment success is patient non-adherence to anti-tuberculosis treatment.
OBJECTIVE: To identify the relation between social conditions and treatment adherence in a prospective cohort setting in an intermediate TB burden country.
DESIGN: To identify associations between poor adherence and social conditions, including educational level, type of residence and occupation, we constructed hierarchical logistic regression models.
RESULTS: A total of 551 participants were included in the study. Low educational levels, poor housing and occupations in the construction and manufacturing industries and service sectors were associated with poor adherence; this association was likely to be differentiated by previous history of anti-tuberculosis treatment.
CONCLUSION: Policy making should focus on improving the social conditions of patients by working towards better housing conditions and providing health promoting working conditions to enable treatment adherence.
C1 [Choi, H.; Lee, M.; Kim, Y.; Cho, S-N.] Int TB Res Ctr, Clin Res Sect, Chang Won, South Korea.
[Choi, H.] Korean Inst TB, Dept Res & Dev, Cheongju, South Korea.
[Chung, H.] Korea Univ, Grad Sch, Dept Publ Hlth Sci, Program Embodiment Hlth Soc Interact BK21PLUS, Seoul, South Korea.
[Chung, H.] Korea Univ, Coll Hlth Sci, Sch Hlth Policy & Management, Seoul, South Korea.
[Muntaner, C.] Univ Toronto, DaIla Lana Sch Publ Hlth, Bloomberg Fac Nursing, Toronto, ON, Canada.
[Barry, C. E., III] NIAID, TB Res Sect, Lab Clin Infect Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Cho, S-N.] Yonsei Univ, Coll Med, Project Med Sci BK21PLUS, Dept Microbiol, Seoul, South Korea.
[Cho, S-N.] Yonsei Univ, Coll Med, Project Med Sci BK21PLUS, Inst Immunol & Immunol Dis, Seoul, South Korea.
RP Chung, H (reprint author), B-365,Hana Sci Hall,145 Anam Ro, Seoul, South Korea.
EM hpolicy@korea.ac.kr
FU Intramural Research Program of the National Institute of Allergy and
Infectious Diseases (NIAID), US National Institutes of Health (NIH),
Bethesda, MD, USA; Korean Centers for Disease Control of the Korean
Ministry of Health and Welfare, Seoul; Social Science Korea Program
through the National Research Foundation of Korea, Daejeon; Ministry of
Education, Seoul, South Korea [NRF-2012S1A5A8022889]
FX This study was supported in part by the Intramural Research Program of
the National Institute of Allergy and Infectious Diseases (NIAID), US
National Institutes of Health (NIH), Bethesda, MD, USA, in part by
continuous support from the Korean Centers for Disease Control of the
Korean Ministry of Health and Welfare, Seoul, to the International
Tuberculosis Research Center, Masan, and in part by the Social Science
Korea Program through the National Research Foundation of Korea,
Daejeon, funded by the Ministry of Education, Seoul, South Korea,
(NRF-2012S1A5A8022889). The authors would like to thank the patients who
enrolled in this research study and the clinical staff who supported the
trial.
NR 33
TC 1
Z9 1
U1 4
U2 5
PU INT UNION AGAINST TUBERCULOSIS LUNG DISEASE (I U A T L D)
PI PARIS
PA 68 BOULEVARD SAINT-MICHEL,, 75006 PARIS, FRANCE
SN 1027-3719
EI 1815-7920
J9 INT J TUBERC LUNG D
JI Int. J. Tuberc. Lung Dis.
PD JUL
PY 2016
VL 20
IS 7
BP 948
EP 954
DI 10.5588/ijtld.15.0759
PG 7
WC Infectious Diseases; Respiratory System
SC Infectious Diseases; Respiratory System
GA DP0ON
UT WOS:000378189200019
PM 27287649
ER
PT J
AU Kacanek, D
Malee, K
Mellins, CA
Tassiopoulos, K
Smith, R
Grant, M
Lee, S
Siddiqui, DQ
Puga, A
AF Kacanek, Deborah
Malee, Kathleen
Mellins, Claude A.
Tassiopoulos, Katherine
Smith, Renee
Grant, Mitzie
Lee, Sonia
Siddiqui, Danish Q.
Puga, Ana
TI Exposure to Violence and Virologic and Immunological Outcomes Among
Youth With Perinatal HIV in the Pediatric HIV/AIDS Cohort Study
SO JOURNAL OF ADOLESCENT HEALTH
LA English
DT Article
DE Violence; Adolescents; Gender; Virologic suppression; Adherence
ID INTIMATE PARTNER VIOLENCE; HUMAN-IMMUNODEFICIENCY-VIRUS; NEGATIVE LIFE
EVENTS; OF-THE-LITERATURE; CHILDHOOD ADVERSITIES; DOMESTIC VIOLENCE;
INFECTION; CHILDREN; ADOLESCENTS; ABUSE
AB Purpose: Exposure to violence in childhood has been linked to adverse health outcomes. Little is known about the prevalence and relationship of youth and caregiver violence exposure to clinical outcomes among youth with perinatal human immunodeficiency virus (HIV) infection (PHIV). We evaluated associations of youth and caregiver violence exposure with unsuppressed viral load (VL) (HIV RNA > 400 copies/mL) and CD4% < 25% among 8- to 15-year-old participants with PHIV in the Pediatric HIV/AIDS Cohort Study Adolescent Master Protocol.
Methods: Annual clinical examination, record abstraction, and interview data were collected, including youth report of recent exposure to violence and caregivers' self-report of being assaulted/abused in adulthood. Multivariable logistic regression methods were used to calculate adjusted odds ratios for unsuppressed VL and CD4% < 25%, controlling for sociodemographic characteristics.
Results: Among 268 youth with PHIV (53% girls, mean age 12.8 years, 21% white, 42% with household income <$ 20,000/year), 34% reported past year violence exposure; 30% had a caregiver who reported being assaulted in adulthood. One quarter of youth (24%) had unsuppressed VL and 22% had CD4% < 25%. Youth who were exposed to violence in the past year versus those who were not had elevated odds of unsuppressed VL. Youth with indirect exposure to violence in the past year versus those without had elevated odds of unsuppressed VL and CD4% < 25% in adjusted models.
Conclusions: Youth with PHIV report a high prevalence of recent violence exposure, which was associated with poor virologic and immunologic outcomes. Reducing violence and providing support to youth with violence exposure and PHIV may improve health outcomes. (C) 2016 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.
C1 [Kacanek, Deborah] Harvard Univ, TH Chan Sch Publ Hlth, Dept Biostat, Ctr Biostat AIDS Res, Boston, MA 02115 USA.
[Malee, Kathleen] Northwestern Univ, Feinberg Sch Med, Dept Psychiat & Behav Sci, Chicago, IL 60611 USA.
[Mellins, Claude A.] Columbia Univ, Dept Psychiat, Med Ctr, HIV Ctr Clin & Behav Studies, New York, NY USA.
[Tassiopoulos, Katherine] Harvard Univ, TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Smith, Renee] Univ Illinois, Dept Pediat, Chicago, IL USA.
[Grant, Mitzie] Drexel Univ, Coll Med, Dept Psychiat, Philadelphia, PA 19104 USA.
[Grant, Mitzie] St Christophers Hosp Children, Philadelphia, PA 19133 USA.
[Lee, Sonia] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Maternal & Pediat Infect Dis Branch, Bethesda, MD USA.
[Siddiqui, Danish Q.] Tulane Sch Med, Dept Pediat Infect Dis, New Orleans, LA USA.
[Puga, Ana] Childrens Diagnost & Treatment Ctr, Ft Lauderdale, FL USA.
RP Kacanek, D (reprint author), Harvard Univ, TH Chan Sch Publ Hlth, Ctr Biostat AIDS Res, 665 Huntington Ave,FXB 505, Boston, MA 02115 USA.
EM dkacanek@sdac.harvard.edu
FU NICHD NIH HHS [U01 HD052102, U01 HD052104]
NR 39
TC 2
Z9 2
U1 1
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1054-139X
EI 1879-1972
J9 J ADOLESCENT HEALTH
JI J. Adolesc. Health
PD JUL
PY 2016
VL 59
IS 1
BP 30
EP 37
DI 10.1016/j.jadohealth.2016.03.004
PG 8
WC Psychology, Developmental; Public, Environmental & Occupational Health;
Pediatrics
SC Psychology; Public, Environmental & Occupational Health; Pediatrics
GA DP0TL
UT WOS:000378202300007
PM 27089837
ER
PT J
AU Hinkle, SN
Albert, PS
Sjaarda, LA
Grewal, J
Grantz, KL
AF Hinkle, Stefanie N.
Albert, Paul S.
Sjaarda, Lindsey A.
Grewal, Jagteshwar
Grantz, Katherine L.
TI Trajectories of maternal gestational weight gain and child cognition
assessed at 5 years of age in a prospective cohort study
SO JOURNAL OF EPIDEMIOLOGY AND COMMUNITY HEALTH
LA English
DT Article
ID BRAIN-DEVELOPMENT; PREGNANCY; ASSOCIATIONS; ADOLESCENCE; OUTCOMES;
MOTHERS; GROWTH; MODELS; BIRTH; WOMEN
AB Background There has been concern that low gestational weight gain may cause poor fetal neurodevelopment.
Methods The association between maternal weight gain and child IQ was examined using serial antenatal weight measurements (median 12) from a prospective cohort of non-obese Scandinavian women (1986-1988). Linear mixed models with piecewise regression were used to estimate participants' (n = 552) trimester-specific average rate of weight gain. Linear regression was used to assess the association between weight gain and children's (n= 344) full-scale, performance and verbal IQ measured at age 5 using the Wechsler Preschool and Primary Scales of Intelligence-Revised.
Results Children born to mothers who gained below versus within the 2nd trimester 2009 recommendations tended to have lower IQ scores (Full-scale: 106.6 (SD 15.1) vs 110.2 (15.2), p = 0.04; verbal: 102.5 (14.3) vs 105.0 (14.9), p = 0.10; performance: 109.5 (15.4) vs 113.4 (14.5), p = 0.03). After adjustment there were no differences in child IQ by weight gain adequacy (full-scale: beta(below)=-1.1 (95% CI -5.1 to 2.9), beta(above) = 1.5 (-3.8 to 6.8); verbal: beta(below) =-0.2 (-3.1 to 2.6), beta(above) = 1.8 (-3.6 to 7.3); performance beta(below) =-1.2 (-4.6 to 2.2), beta(above) = 1.0 (-4.6 to 6.7)). No differences were observed based on 3rd trimester adequacy. No differences were observed in IQ scores by quintile of weight gain for any trimester, particularly after adjustment for maternal IQ.
Conclusions Our findings are reassuring that among normal weight women, pregnancy weight gain is not associated with child cognitive development. Further investigation should be conducted in contemporary cohorts that also include obese mothers, who are at the greatest risk for low weight gain.
C1 [Hinkle, Stefanie N.; Sjaarda, Lindsey A.; Grantz, Katherine L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Intramural Populat Hlth Res, NIH, 6100 Execut Blvd Room 7B03, Bethesda, MD 20892 USA.
[Albert, Paul S.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Biostat & Bioinformat Branch, Div Intramural Populat Hlth Res, NIH, 6100 Execut Blvd Room 7B03, Bethesda, MD 20892 USA.
[Grewal, Jagteshwar] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Off Director, Div Intramural Populat Hlth Res, NIH, 6100 Execut Blvd Room 7B03, Bethesda, MD 20892 USA.
RP Hinkle, SN (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Intramural Populat Hlth Res, NIH, 6100 Execut Blvd Room 7B03, Bethesda, MD 20892 USA.
EM hinklesn@mail.nih.gov
OI Hinkle, Stefanie/0000-0003-4312-708X; Sjaarda,
Lindsey/0000-0003-0539-8110; Grewal, Jagteshwar/0000-0002-0141-4876;
Grantz, Katherine/0000-0003-0276-8534
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development, National Institutes of Health
FX This research was supported by the intramural research program of the
Eunice Kennedy Shriver National Institute of Child Health and Human
Development, National Institutes of Health.
NR 32
TC 1
Z9 1
U1 2
U2 3
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0143-005X
EI 1470-2738
J9 J EPIDEMIOL COMMUN H
JI J. Epidemiol. Community Health
PD JUL
PY 2016
VL 70
IS 7
BP 696
EP 703
DI 10.1136/jech-2014-205108
PG 8
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA DO8UY
UT WOS:000378061200010
PM 26759126
ER
PT J
AU Roche, J
Ying, JF
Shen, Y
Torchia, DA
Bax, A
AF Roche, Julien
Ying, Jinfa
Shen, Yang
Torchia, Dennis A.
Bax, Ad
TI ARTSY-J: Convenient and precise measurement of (3)J(HNH alpha) couplings
in medium-size proteins from TROSY-HSQC spectra
SO JOURNAL OF MAGNETIC RESONANCE
LA English
DT Article
DE Backbone torsion angle; Gly; Karplus equation; TROSY; GB3; HIV-1
Protease; Protein NMR
ID RESIDUAL DIPOLAR COUPLINGS; CHEMICAL-SHIFT PREDICTION; RESOLVED
NMR-SPECTROSCOPY; HIV-1 PROTEASE; PERDEUTERATED PROTEINS; ACCURATE
MEASUREMENTS; KARPLUS EQUATIONS; CONSTANTS; RELAXATION; DYNAMICS
AB A new and convenient method, named ARTSY-j, is introduced that permits extraction of the (3)J(HNH alpha) couplings in proteins from the relative intensities in a pair of N-15-H-1 TROSY-HSQC spectra. The pulse scheme includes (3)J(HNH alpha) dephasing of the narrower TROSY H-1(N)-{N-15) doublet component during a delay, integrated into the regular two-dimensional TROSY-HSQC pulse scheme, and compares the obtained intensity with a reference spectrum where (3)J(HNH alpha) dephasing is suppressed. The effect of passive H-1(alpha) spin flips downscales the apparent (3)J(HNH alpha) coupling by a uniform factor that depends approximately linea(r)ly on both the duration of the (3)J(HNH alpha) dephasing delay and the H-1-H-1 cross relaxation rate. Using such a correction factor, which accounts for the effects of both inhomogeneity of the radiofrequency field and H-1(alpha) spin flips, agreement between prior and newly measured values for the small model protein GB3 is better than 0.3 Hz. Measurement for the HIV-1 protease homodimer (22 kDa) yields (3)J(HNH alpha) values that agree to better than 0.7 Hz with predictions made on the basis of a previously parameterized Karplus equation. Although for Gly residues the two individual (3)J(HNH alpha) couplings cannot be extracted from a single set of ARTSY-J spectra, the measurement provides valuable phi angle information. Published by Elsevier Inc.
C1 [Roche, Julien; Ying, Jinfa; Shen, Yang; Torchia, Dennis A.; Bax, Ad] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
RP Bax, A (reprint author), NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
EM bax@nih.gov
RI Shen, Yang/C-3064-2008
OI Shen, Yang/0000-0003-1408-8034
FU Intramural Research Program of the National Institute of Diabetes and
Digestive and Kidney Diseases; Intramural Antiviral Target Program of
the Office of the Director, NIH
FX We thank John Louis for preparing the protease sample, and Fang Li for
the GB3 sample. This work was supported by the Intramural Research
Program of the National Institute of Diabetes and Digestive and Kidney
Diseases and the Intramural Antiviral Target Program of the Office of
the Director, NIH.
NR 47
TC 0
Z9 0
U1 4
U2 8
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1090-7807
EI 1096-0856
J9 J MAGN RESON
JI J. Magn. Reson.
PD JUL
PY 2016
VL 268
BP 73
EP 81
DI 10.1016/j.jmr.2016.05.001
PG 9
WC Biochemical Research Methods; Physics, Atomic, Molecular & Chemical;
Spectroscopy
SC Biochemistry & Molecular Biology; Physics; Spectroscopy
GA DP0NG
UT WOS:000378185900009
PM 27179455
ER
PT J
AU Therkelsen, KE
Preis, SR
Beiser, A
DeCarli, C
Seshadri, S
Wolf, P
Au, R
Fox, CS
AF Therkelsen, Kate E.
Preis, Sarah R.
Beiser, Alexa
DeCarli, Charles
Seshadri, Sudha
Wolf, Philip
Au, Rhoda
Fox, Caroline S.
TI Neck Circumference, Brain Imaging Measures, and Neuropsychological
Testing Measures
SO JOURNAL OF STROKE & CEREBROVASCULAR DISEASES
LA English
DT Article
DE Epidemiology; population studies; cognition; adiposity
ID OBSTRUCTIVE SLEEP-APNEA; BODY-MASS INDEX; INTIMA-MEDIA THICKNESS;
COGNITIVE PERFORMANCE; CENTRAL OBESITY; FRAMINGHAM; RISK; DEMENTIA;
VOLUME; IMPAIRMENT
AB Background: Perivascular fat may have direct effects on local vascularity. Neck fat is associated with carotid intimal thickness, a predictor of brain aging outcomes. This study investigated whether neck circumference, an estimation of neck fat, has unique associations with brain aging outcomes. Methods: The study sample (n = 2082, 53.5% women, mean age 60.9 years) was derived from Framingham Heart Study participants with brain magnetic resonance imaging (MRI) and neuropsychological (NP) test measures. Multivariable-adjusted regressions examined crosssectional associations of neck circumference with brain MRI and NP test measures. Models were also constructed with waist circumference and body mass index (BMI) as exposures. Results: A 1 standard deviation (2.8 cm [women]; 2.9 cm [men]) increment in neck circumference was associated with lower total cerebral brain volume (beta = -.22, P = .0006) and lower frontal brain volume (beta = -.55, P < .0001). However, a similar association was observed for both waist circumference and BMI. There were no associations between neck circumference and NP test measures after full covariate adjustment. Conclusions: There were no unique associations between neck circumference and brain MRI or NP measures. Consistent with prior observations, all adiposity measures showed associations with more adverse brain MRI and NP measures, suggesting a global association of generalized adiposity.
C1 [Therkelsen, Kate E.; Fox, Caroline S.] NHLBI, Framingham Heart Study, 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA.
[Therkelsen, Kate E.] Boston Univ, Sch Med, Boston, MA 02118 USA.
[Preis, Sarah R.; Beiser, Alexa] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Beiser, Alexa; Seshadri, Sudha; Wolf, Philip; Au, Rhoda] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA.
[Fox, Caroline S.] Univ Calif Davis, Dept Neurol, Sacramento, CA 95817 USA.
[Fox, Caroline S.] Univ Calif Davis, Ctr Neurosci, Sacramento, CA 95817 USA.
[Fox, Caroline S.] Brigham & Womens Hosp, Div Endocrinol & Metab, 75 Francis St, Boston, MA 02115 USA.
[Fox, Caroline S.] Harvard Univ, Sch Med, Boston, MA USA.
RP Fox, CS (reprint author), NHLBI, Framingham Heart Study, 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA.
EM foxca@nhlbi.nih.gov
OI Beiser, Alexa/0000-0001-8551-7778
FU Framingham Heart Study of the National Heart, Lungand Blood Institute
[N01-HC-25195]
FX The Framingham Heart Study of the National Heart, Lungand Blood
Institute is supported by contract N01-HC-25195.
NR 33
TC 0
Z9 0
U1 1
U2 1
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1052-3057
EI 1532-8511
J9 J STROKE CEREBROVASC
JI J. Stroke Cerebrovasc. Dis.
PD JUL
PY 2016
VL 25
IS 7
BP 1570
EP 1581
DI 10.1016/j.jstrokecerebrovasdis.2016.02.016
PG 12
WC Neurosciences; Peripheral Vascular Disease
SC Neurosciences & Neurology; Cardiovascular System & Cardiology
GA DO7ZW
UT WOS:000378002800003
PM 27056441
ER
PT J
AU Kwon, YD
Georgiev, IS
Ofek, G
Zhang, BS
Asokan, M
Bailer, RT
Bao, A
Caruso, W
Chen, XJ
Choe, M
Druz, A
Ko, SY
Louder, MK
McKee, K
O'Dell, S
Pegu, A
Rudicell, RS
Shi, W
Wang, KY
Yang, YP
Alger, M
Bender, MF
Carlton, K
Cooper, JW
Blinn, J
Eudailey, J
Lloyd, K
Parks, R
Alam, SM
Haynes, BF
Padte, NN
Yu, J
Ho, DD
Huang, JH
Connors, M
Schwartz, RM
Mascola, JR
Kwong, PD
AF Kwon, Young D.
Georgiev, Ivelin S.
Ofek, Gilad
Zhang, Baoshan
Asokan, Mangaiarkarasi
Bailer, Robert T.
Bao, Amy
Caruso, William
Chen, Xuejun
Choe, Misook
Druz, Aliaksandr
Ko, Sung-Youl
Louder, Mark K.
McKee, Krisha
O'Dell, Sijy
Pegu, Amarendra
Rudicell, Rebecca S.
Shi, Wei
Wang, Keyun
Yang, Yongping
Alger, Mandy
Bender, Michael F.
Carlton, Kevin
Cooper, Jonathan W.
Blinn, Julie
Eudailey, Joshua
Lloyd, Krissey
Parks, Robert
Alam, S. Munir
Haynes, Barton F.
Padte, Neal N.
Yu, Jian
Ho, David D.
Huang, Jinghe
Connors, Mark
Schwartz, Richard M.
Mascola, John R.
Kwong, Peter D.
TI Optimization of the Solubility of HIV-1-Neutralizing Antibody 10E8
through Somatic Variation and Structure-Based Design
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID PROXIMAL EXTERNAL REGION; MONOCLONAL-ANTIBODIES; HIV-1 NEUTRALIZATION;
POTENT NEUTRALIZATION; IMPROVES PROTECTION; GLYCOPROTEIN GP41; ENVELOPE
TRIMER; IN-VIVO; MEMBRANE; BROAD
AB Extraordinary antibodies capable of near pan-neutralization of HIV-1 have been identified. One of the broadest is antibody 10E8, which recognizes the membrane-proximal external region (MPER) of the HIV-1 envelope and neutralizes > 95% of circulating HIV-1 strains. If delivered passively, 10E8 might serve to prevent or treat HIV-1 infection. Antibody 10E8, however, is markedly less soluble than other antibodies. Here, we describe the use of both structural biology and somatic variation to develop optimizedversions of 10E8 with increased solubility. From the structure of 10E8, we identified a prominent hydrophobic patch; reversion of four hydrophobic residues in this patch to their hydrophilic germ line counterparts resulted in an similar to 10-fold decrease in turbidity. We also used somatic variants of 10E8, identified previously by next-generation sequencing, to optimize heavy and light chains; this process yielded several improved variants. Of these, variant 10E8v4 with 26 changes versus the parent 10E8 was the most soluble, with a paratope we showed crystallographically to be virtually identical to that of 10E8, a potency on a panel of 200 HIV-1 isolates also similar to that of 10E8, and a half-life in rhesus macaques of similar to 10 days. An anomaly in 10E8v4 size exclusion chromatography that appeared to be related to conformational isomerization was resolved by engineering an interchain disulfide. Thus, by combining a structure-based approach with natural variation in potency and solubility from the 10E8 lineage, we successfully created variants of 10E8 which retained the potency and extraordinary neutralization breadth of the parent 10E8 but with substantially increased solubility.
IMPORTANCE
Antibody 10E8 could be used to prevent HIV-1 infection, if manufactured and delivered economically. It suffers, however, from issues of solubility, which impede manufacturing. We hypothesized that the physical characteristic of 10E8 could be improved through rational design, without compromising breadth and potency. We used structural biology to identify hydrophobic patches on 10E8, which did not appear to be involved in 10E8 function. Reversion of hydrophobic residues in these patches to their hydrophilic germ line counterparts increased solubility. Next, clues from somatic variants of 10E8, identified by next-generation sequencing, were incorporated. A combination of structure-based design and somatic variant optimization led to 10E8v4, with substantially improved solubility and similar potency compared to the parent 10E8. The cocrystal structure of antibody 10E8v4 with its HIV-1 epitope was highly similar to that with the parent 10E8, despite 26 alterations in sequence and substantially improved solubility. Antibody 10E8v4 may be suitable for manufacturing.
C1 [Kwon, Young D.; Georgiev, Ivelin S.; Ofek, Gilad; Zhang, Baoshan; Asokan, Mangaiarkarasi; Bailer, Robert T.; Bao, Amy; Caruso, William; Chen, Xuejun; Choe, Misook; Druz, Aliaksandr; Ko, Sung-Youl; Louder, Mark K.; McKee, Krisha; O'Dell, Sijy; Pegu, Amarendra; Rudicell, Rebecca S.; Shi, Wei; Wang, Keyun; Yang, Yongping; Alger, Mandy; Bender, Michael F.; Carlton, Kevin; Cooper, Jonathan W.; Schwartz, Richard M.; Mascola, John R.; Kwong, Peter D.] NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Blinn, Julie; Eudailey, Joshua; Lloyd, Krissey; Parks, Robert; Alam, S. Munir; Haynes, Barton F.] Duke Univ, Sch Med, Dept Med, Duke Human Vaccine Inst, Durham, NC 27706 USA.
[Blinn, Julie; Eudailey, Joshua; Lloyd, Krissey; Parks, Robert; Alam, S. Munir; Haynes, Barton F.] Duke Univ, Sch Med, Dept Surg, Duke Human Vaccine Inst, Durham, NC USA.
[Blinn, Julie; Eudailey, Joshua; Lloyd, Krissey; Parks, Robert; Alam, S. Munir; Haynes, Barton F.] Duke Univ, Dept Pediat, Sch Med, Duke Human Vaccine Inst, Durham, NC 27706 USA.
[Blinn, Julie; Eudailey, Joshua; Lloyd, Krissey; Parks, Robert; Alam, S. Munir; Haynes, Barton F.] Duke Univ, Sch Med, Dept Immunol, Duke Human Vaccine Inst, Durham, NC USA.
[Blinn, Julie; Eudailey, Joshua; Lloyd, Krissey; Parks, Robert; Alam, S. Munir; Haynes, Barton F.] Duke Univ, Ctr HIV AIDS Vaccine Immunol Immunogen Discovery, Durham, NC USA.
[Padte, Neal N.; Yu, Jian; Ho, David D.] Rockefeller Univ, Aaron Diamond AIDS Res Ctr, 1230 York Ave, New York, NY 10021 USA.
[Huang, Jinghe; Connors, Mark] NIAID, HIV Specif Immun Sect, Immunoregulat Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
RP Mascola, JR; Kwong, PD (reprint author), NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM jmascola@mail.nih.gov; pdkwong@nih.gov
RI Kwon, Young Do/A-6957-2010
FU Bill and Melinda Gates Foundation [OPP1039775]; Intramural Research
Program, Vaccine Research Center, National Institute of Allergy and
Infectious Diseases (VRC, NIAID) [ZIA AI005022-15]
FX This work, including the efforts of John R. Mascola and Peter D. Kwong,
was funded by Bill and Melinda Gates Foundation (OPP1039775). This work,
including the efforts of Peter D. Kwong, was funded by Intramural
Research Program, Vaccine Research Center, National Institute of Allergy
and Infectious Diseases (VRC, NIAID) (ZIA AI005022-15).
NR 44
TC 7
Z9 7
U1 2
U2 6
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
EI 1098-5514
J9 J VIROL
JI J. Virol.
PD JUL
PY 2016
VL 90
IS 13
BP 5899
EP 5914
DI 10.1128/JVI.03246-15
PG 16
WC Virology
SC Virology
GA DP2SA
UT WOS:000378340300006
PM 27053554
ER
PT J
AU Lavender, KJ
Gibbert, K
Peterson, KE
Van Dis, E
Francois, S
Woods, T
Messer, RJ
Gawanbacht, A
Muller, JA
Munch, J
Phillips, K
Race, B
Harper, MS
Guo, KJ
Lee, EJ
Trilling, M
Hengel, H
Piehler, J
Verheyen, J
Wilson, CC
Santiago, ML
Hasenkrug, KJ
Dittmer, U
AF Lavender, Kerry J.
Gibbert, Kathrin
Peterson, Karin E.
Van Dis, Erik
Francois, Sandra
Woods, Tyson
Messer, Ronald J.
Gawanbacht, Ali
Mueller, Janis A.
Muench, Jan
Phillips, Katie
Race, Brent
Harper, Michael S.
Guo, Kejun
Lee, Eric J.
Trilling, Mirko
Hengel, Hartmut
Piehler, Jacob
Verheyen, Jens
Wilson, Cara C.
Santiago, Mario L.
Hasenkrug, Kim J.
Dittmer, Ulf
TI Interferon Alpha Subtype-Specific Suppression of HIV-1 Infection In Vivo
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID IMMUNODEFICIENCY-VIRUS TYPE-1; HIGH-DOSE INTERFERON; T-CELL-ACTIVATION;
HEPATITIS-C VIRUS; PEGYLATED INTERFERON; PHASE-II; ANTIRETROVIRAL
THERAPY; MEDIATED SUPPRESSION; DISEASE PROGRESSION; DNA DEAMINATION
AB Although all 12 subtypes of human interferon alpha (IFN-alpha) bind the same receptor, recent results have demonstrated that they elicit unique host responses and display distinct efficacies in the control of different viral infections. The IFN-alpha 2 subtype is currently in HIV-1 clinical trials, but it has not consistently reduced viral loads in HIV-1 patients and is not the most effective subtype against HIV-1 in vitro. We now demonstrate in humanized mice that, when delivered at the same high clinical dose, the human IFN-alpha 14 subtype has very potent anti-HIV-1 activity whereas IFN-alpha 2 does not. In both postexposure prophylaxis and treatment of acute infections, IFN-alpha 14, but not IFN-alpha 2, significantly suppressed HIV-1 replication and proviral loads. Furthermore, HIV-1- induced immune hyperactivation, which is a prognosticator of disease progression, was reduced by IFN-alpha 14 but not IFN-alpha 2. Whereas ineffective IFN-alpha 2 therapy was associated with CD8(+) T cell activation, successful IFN-alpha 14 therapy was associated with increased intrinsic and innate immunity, including significantly higher induction of tetherin and MX2, increased APOBEC3G signature mutations in HIV-1 proviral DNA, and higher frequencies of TRAIL(+) NK cells. These results identify IFN-alpha 14 as a potent new therapeutic that operates via mechanisms distinct from those of antiretroviral drugs. The ability of IFN-alpha 14 to reduce both viremia and proviral loads in vivo suggests that it has strong potential as a component of a cure strategy for HIV-1 infections. The broad implication of these results is that the antiviral efficacy of each individual IFN-alpha subtype should be evaluated against the specific virus being treated.
IMPORTANCE
The naturally occurring antiviral protein IFN-alpha 2 is used to treat hepatitis viruses but has proven rather ineffective against HIV in comparison to triple therapy with the antiretroviral (ARV) drugs. Although ARVs suppress the replication of HIV, they fail to completely clear infections. Since IFN-alpha acts by different mechanism than ARVs and has been shown to reduce HIV proviral loads, clinical trials are under way to test whether IFN-alpha 2 combined with ARVs might eradicate HIV-1 infections. IFN-alpha is actually a family of 12 distinct proteins, and each IFN-alpha subtype has different efficacies toward different viruses. Here, we use mice that contain a human immune system, so they can be infected with HIV. With this model, we demonstrate that while IFN-alpha 2 is only weakly effective against HIV, IFN-alpha 14 is extremely potent. This discovery identifies IFN-alpha 14 as a more powerful IFN-alpha subtype for use in combination therapy trials aimed toward an HIV cure.
C1 [Lavender, Kerry J.; Peterson, Karin E.; Van Dis, Erik; Woods, Tyson; Messer, Ronald J.; Phillips, Katie; Race, Brent; Hasenkrug, Kim J.] NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, NIH, Hamilton, MT USA.
[Gibbert, Kathrin; Francois, Sandra; Trilling, Mirko; Verheyen, Jens; Dittmer, Ulf] Univ Duisburg Essen, Univ Hosp Essen, Inst Virol, Essen, Germany.
[Gawanbacht, Ali; Mueller, Janis A.; Muench, Jan] Univ Ulm, Inst Mol Virol, D-89069 Ulm, Germany.
[Hengel, Hartmut] Univ Freiburg, Inst Virol, Univ Med Ctr, Hugstetter Str 55, D-79106 Freiburg, Germany.
[Piehler, Jacob] Univ Osnabruck, Dept Biol, Osnabruck, Germany.
[Harper, Michael S.; Guo, Kejun; Lee, Eric J.; Wilson, Cara C.; Santiago, Mario L.] Univ Colorado Denver, Dept Med, Aurora, CO USA.
RP Hasenkrug, KJ (reprint author), NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, NIH, Hamilton, MT USA.; Dittmer, U (reprint author), Univ Duisburg Essen, Univ Hosp Essen, Inst Virol, Essen, Germany.
EM khasenkrug@nih.gov; ulf.dittmer@uni-due.de
OI Trilling, Mirko/0000-0003-3659-3541
FU HHS \ NIH \ National Institute of Allergy and Infectious Diseases
(NIAID) [ZIA A1001141, R56 AI116271]; Deutsche Forschungsgemeinschaft
(DFG) [DFG TRR60, GRK 1949/1]; International Graduate School in
Molecular Medicine Ulm (fellowship)
FX This work, including the efforts of Kim J. Hasenkrug, was funded by HHS
vertical bar NIH vertical bar National Institute of Allergy and
Infectious Diseases (NIAID) (ZIA A1001141). This work, including the
efforts of Ulf Dittmer, Kathrin Gibbert, and Mirko Trilling, was funded
by Deutsche Forschungsgemeinschaft (DFG) (DFG TRR60 and GRK 1949/1).
This work, including the efforts of Mario L. Santiago, was funded by HHS
vertical bar NIH vertical bar National Institute of Allergy and
Infectious Diseases (NIAID) (R56 AI116271). This work, including the
efforts of Janis A. Mueller, was funded by International Graduate School
in Molecular Medicine Ulm (fellowship).
NR 86
TC 7
Z9 7
U1 2
U2 7
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
EI 1098-5514
J9 J VIROL
JI J. Virol.
PD JUL
PY 2016
VL 90
IS 13
BP 6001
EP 6013
DI 10.1128/JVI.00451-16
PG 13
WC Virology
SC Virology
GA DP2SA
UT WOS:000378340300014
PM 27099312
ER
PT J
AU Rhein, BA
Brouillette, RB
Schaack, GA
Chiorini, JA
Maury, W
AF Rhein, Bethany A.
Brouillette, Rachel B.
Schaack, Grace A.
Chiorini, John A.
Maury, Wendy
TI Characterization of Human and Murine T-Cell Immunoglobulin Mucin Domain
4 (TIM-4) IgV Domain Residues Critical for Ebola Virus Entry
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID APOPTOTIC CELLS; PHOSPHATIDYLSERINE RECEPTOR; ZAIRE-EBOLAVIRUS; MEMBRANE
PHOSPHATIDYLSERINE; MARBURG VIRUSES; LIPID RAFTS; GLYCOPROTEIN;
ACTIVATION; IDENTIFICATION; BINDING
AB Phosphatidylserine (PtdSer) receptors that are responsible for the clearance of dying cells have recently been found to mediate enveloped virus entry. Ebola virus (EBOV), a member of the Filoviridae family of viruses, utilizes PtdSer receptors for entry into target cells. The PtdSer receptors human and murine T-cell immunoglobulin mucin (TIM) domain proteins TIM-1 and TIM-4 mediate filovirus entry by binding to PtdSer on the virion surface via a conserved PtdSer binding pocket within the amino-terminal IgV domain. While the residues within the TIM-1 IgV domain that are important for EBOV entry are characterized, the molecular details of virion-TIM-4 interactions have yet to be investigated. As sequences and structural alignments of the TIM proteins suggest distinct differences in the TIM-1 and TIM-4 IgV domain structures, we sought to characterize TIM-4 IgV domain residues required for EBOV entry. Using vesicular stomatitis virus pseudovirions bearing EBOV glycoprotein (EBOV GP/VSV Delta G), we evaluated virus binding and entry into cells expressing TIM-4 molecules mutated within the IgV domain, allowing us to identify residues important for entry. Similar to TIM-1, residues in the PtdSer binding pocket of murine and human TIM-4 (mTIM-4 and hTIM-4) were found to be important for EBOV entry. However, additional TIM-4-specific residues were also found to impact EBOV entry, with a total of 8 mTIM-4 and 14 hTIM-4 IgV domain residues being critical for virion binding and internalization. Together, these findings provide a greater understanding of the interaction of TIM-4 with EBOV virions.
C1 [Rhein, Bethany A.; Brouillette, Rachel B.; Schaack, Grace A.; Maury, Wendy] Univ Iowa, Dept Microbiol, Iowa City, IA 52242 USA.
[Chiorini, John A.] Natl Inst Dent & Craniofacial Res, Mol Physiol & Therapeut Branch, NIH, Bethesda, MD USA.
RP Maury, W (reprint author), Univ Iowa, Dept Microbiol, Iowa City, IA 52242 USA.
EM wendy-maury@uiowa.edu
FU HHS \ National Institutes of Health (NIH); HHS \ NIH \ National
Institute of Allergy and Infectious Diseases (NIAID) [R01AI077519, U54
AI057160]
FX This work, including the efforts of John A. Chiorini, was funded by HHS
vertical bar National Institutes of Health (NIH) (intramural funds).
This work, including the efforts of Wendy Maury, was funded by HHS
vertical bar NIH vertical bar National Institute of Allergy and
Infectious Diseases (NIAID) (R01AI077519 and U54 AI057160).
NR 59
TC 1
Z9 1
U1 6
U2 9
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
EI 1098-5514
J9 J VIROL
JI J. Virol.
PD JUL
PY 2016
VL 90
IS 13
BP 6097
EP 6111
DI 10.1128/JVI.00100-16
PG 15
WC Virology
SC Virology
GA DP2SA
UT WOS:000378340300022
PM 27122575
ER
PT J
AU Belsher, BE
Jaycox, LH
Freed, MC
Evatt, DP
Liu, X
Novak, LA
Zatzick, D
Bray, RM
Engel, CC
AF Belsher, Bradley E.
Jaycox, Lisa H.
Freed, Michael C.
Evatt, Daniel P.
Liu, Xian
Novak, Laura A.
Zatzick, Douglas
Bray, Robert M.
Engel, Charles C.
TI Mental Health Utilization Patterns During a Stepped, Collaborative Care
Effectiveness Trial for PTSD and Depression in the Military Health
System
SO MEDICAL CARE
LA English
DT Article
DE service utilization; collaborative care; stepped-care; mental health
ID POSTTRAUMATIC-STRESS-DISORDER; INTERVENTION; METAANALYSIS; DEPLOYMENT;
VALIDITY; MODELS; SAMPLE
AB Background: Integrated health care models aim to improve access and continuity of mental health services in general medical settings. STEPS-UP is a stepped, centrally assisted collaborative care model designed to improve posttraumatic stress disorder (PTSD) and depression care by providing the appropriate intensity and type of care based on patient characteristics and clinical complexity. STEPS-UP demonstrated improved PTSD and depression outcomes in a large effectiveness trial conducted in the Military Health System. The objective of this study was to examine differences in mental health utilization patterns between patients in the stepped, centrally assisted collaborative care model relative to patients in the collaborative care as usual-treatment arm.
Methods: Patients with probable PTSD and/or depression were recruited at 6 large military treatment facilities, and 666 patients were enrolled and randomized to STEPS-UP or usual collaborative care. Utilization data acquired from Military Health System administrative datasets were analyzed to determine mental health service use and patterns. Clinical complexity and patient characteristics were based on self-report questionnaires collected at baseline.
Results: Compared with the treatment as usual arm, STEPS-UP participants received significantly more mental health services and psychiatric medications across primary and specialty care settings during the year of their participation. Patterns of service use indicated that greater clinical complexity was associated with increased service use in the STEPS-UP group, but not in the usual care group.
Conclusions: Results suggest that stepped, centrally assisted collaborative care models may increase the quantity of mental health services patients receive, while efficiently matching care on the basis of the clinical complexity of patients.
C1 [Belsher, Bradley E.; Evatt, Daniel P.; Liu, Xian; Novak, Laura A.] Def Ctr Excellence Psychol Hlth & Traumat Brain I, Deployment Hlth Clin Ctr, 1335 East West Highway,3rd Floor,Suite 3-100, Silver Spring, MD 20910 USA.
[Belsher, Bradley E.; Liu, Xian; Engel, Charles C.] Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA.
[Jaycox, Lisa H.; Engel, Charles C.] RAND Corp, Arlington, VA USA.
[Freed, Michael C.] NIMH, Div Serv & Intervent Res, Bethesda, MD 20892 USA.
[Zatzick, Douglas] Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA.
[Bray, Robert M.] RTI Int, Res Triangle Pk, NC USA.
RP Belsher, BE (reprint author), Def Ctr Excellence Psychol Hlth & Traumat Brain I, Deployment Hlth Clin Ctr, 1335 East West Highway,3rd Floor,Suite 3-100, Silver Spring, MD 20910 USA.
EM bradley.e.belsher.civ@mail.mil
FU US Department of Defense Deployment Related Medical Research Program
award [DR080409]; [W81XWH-09-2-0077]; [W81XWH-09-2-0078];
[W81XWH-09-2-0079]
FX Supported by a US Department of Defense Deployment Related Medical
Research Program award (Grant DR080409). The award was a joint award to
the Henry M. Jackson Foundation for the Advancement of Military Medicine
Inc. (award W81XWH-09-2-0077), Research Triangle Institute (award
W81XWH-09-2-0078), and RAND Corporation (award W81XWH-09-2-0079). The
sponsor had no role in study design; in the collection, analysis and
interpretation of data; in the writing of the report; or in the decision
to submit the article for publication. The views expressed in this
article are those of the authors and do not necessarily represent the
views of the Department of Defense, the US Government, or any other
organization or agency, public or private.
NR 37
TC 1
Z9 1
U1 1
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0025-7079
EI 1537-1948
J9 MED CARE
JI Med. Care
PD JUL
PY 2016
VL 54
IS 7
BP 706
EP 713
PG 8
WC Health Care Sciences & Services; Health Policy & Services; Public,
Environmental & Occupational Health
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health
GA DO8UW
UT WOS:000378061000010
PM 27111751
ER
PT J
AU Demidowich, AP
Davis, AI
Dedhia, N
Yanovski, JA
AF Demidowich, Andrew P.
Davis, Angela I.
Dedhia, Nicket
Yanovski, Jack A.
TI Colchicine to decrease NLRP3-activated inflammation and improve
obesity-related metabolic dysregulation
SO MEDICAL HYPOTHESES
LA English
DT Article
ID C-REACTIVE PROTEIN; FAMILIAL MEDITERRANEAN FEVER; NECROSIS-FACTOR-ALPHA;
NF-KAPPA-B; ISLET AMYLOID POLYPEPTIDE; LIFE-STYLE INTERVENTION;
DIET-INDUCED OBESITY; ASPIRIN-LIKE DRUGS; INSULIN-RESISTANCE;
ADIPOSE-TISSUE
AB Obesity is a major risk-factor for the development of insulin resistance, type 2 diabetes, and cardiovascular disease. Circulating molecules associated with obesity, such as saturated fatty acids and cholesterol crystals, stimulate the innate immune system to incite a chronic inflammatory state. Studies in mouse models suggest that suppressing the obesity-induced chronic inflammatory state may prevent or reverse obesity-associated metabolic dysregulation. Human studies, however, have been far less positive, possibly because targeted interventions were too far downstream of the inciting inflammatory events. Recently, it has been shown that, within adipose tissue macrophages, assembly of a multi-protein member of the innate immune system, the NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome, is essential for the induction of this inflammatory state. Microtubules enable the necessary spatial arrangement of the components of the NLRP3 inflammasome in the cell, leading to its activation and propagation of the inflammatory cascade. Colchicine, a medication classically used for gout, mediates its anti-inflammatory effect by inhibiting tubulin polymerization, and has been shown to attenuate macrophage NLRP3 inflammasome arrangement and activation in vitro and in vivo. Given these findings, we hypothesize that, in at-risk individuals (those with obesity-induced inflammation and metabolic dysregulation), long-term colchicine use will lead to suppression of inflammation and thus cause improvements in insulin sensitivity and other obesity-related metabolic impairments. Published by Elsevier Ltd.
C1 [Demidowich, Andrew P.; Davis, Angela I.; Dedhia, Nicket; Yanovski, Jack A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Growth & Obes, Div Translat Med, NIH,DHHS, Bethesda, MD 20892 USA.
RP Demidowich, AP (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Growth & Obes, NIH, Hatfield Clin Res Ctr CRC, 10 Ctr Dr,Room 1-3330,MSC 1103, Bethesda, MD 20892 USA.
EM andrew.demidowich@nih.gov
FU Division of Intramural Research of the Eunice Kennedy Shriver National
Institute of Child Health and Human Development (NICHD), NIH
[ZIAHD00641]; NICHD Director's Investigator Award; Zafgen Inc.
FX This research was supported by the Division of Intramural Research of
the Eunice Kennedy Shriver National Institute of Child Health and Human
Development (NICHD), NIH ZIAHD00641 (to JAY) with supplemental funding
from an NICHD Director's Investigator Award (to JAY and APD). Dr.
Yanovski reports receiving grant funding from Zafgen Inc. for a clinical
trial of pharmacotherapy to treat obesity and hyperphagia in patients
with the Prader-Willi syndrome. No sponsors were involved in the
collection, analysis, or interpretation of data; writing of the
manuscript; or decision to submit the manuscript for publication.
NR 100
TC 2
Z9 2
U1 1
U2 4
PU CHURCHILL LIVINGSTONE
PI EDINBURGH
PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE,
LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND
SN 0306-9877
EI 1532-2777
J9 MED HYPOTHESES
JI Med. Hypotheses
PD JUL
PY 2016
VL 92
BP 67
EP 73
DI 10.1016/j.mehy.2016.04.039
PG 7
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA DP0LZ
UT WOS:000378182600018
PM 27241260
ER
PT J
AU Fishman, EI
Steeves, JA
Zipunnikov, V
Koster, A
Berrigan, D
Harris, TA
Murphy, R
AF Fishman, Ezra I.
Steeves, Jeremy A.
Zipunnikov, Vadim
Koster, Annemarie
Berrigan, David
Harris, Tamara A.
Murphy, Rachel
TI Association between Objectively Measured Physical Activity and Mortality
in NHANES
SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE
LA English
DT Article
DE ACCELEROMETER; LIGHT ACTIVITY; MODERATETO-VIGOROUS PHYSICAL ACTIVITY;
PROSPECTIVE COHORT STUDY; SEDENTARY
ID ALL-CAUSE MORTALITY; SEDENTARY BEHAVIOR; US ADULTS; OLDER-ADULTS; TIME;
ACCELEROMETER; INTENSITY; METAANALYSIS; HEALTH; RISK
AB Purpose: We examined total activity, light activity, and moderate-to-vigorous physical activity (MVPA) as predictors of mortality in a nationally representative sample of older adults. Then we explored the theoretical consequences of replacing sedentary time with the same duration of light activity or MVPA. Methods: Using accelerometer-measured activity, the associations between total activity, light activity (100-2019 counts per minute), and MVPA (92019 counts per minute) counts and mortality were examined in adults age 50 to 79 yr in the National Health and Nutrition Examination Survey, 2003-2006 (n = 3029), with mortality follow-up through December 2011. Cox proportional hazard models were fitted to estimate mortality risks. An isotemporal substitution model was used to examine the theoretical consequences of replacing sedentary time with light activity or MVPA on mortality. Results: After adjusting for potential confounders, including age, sex, race/ethnicity, education, BMI, and the presence of comorbid conditions, those in the highest tertile of total activity counts had one fifth the risk of death of those in the lowest tertile (hazard ratio [HR] = 0.21, 95% confidence interval [CI] = 0.12-0.38), and those in the middle tertile had one third the risk of death (HR = 0.36, 95% CI = 0.30-0.44). In addition, replacing 30 min of sedentary time with light activity was associated with significant reduction in mortality risk (after 5 yr of follow-up: HR = 0.80, 95% CI = 0.75-0.85). Replacing 30 min of sedentary time with MVPA was also associated with reduction in mortality risk (HR = 0.49, 95% CI = 0.25-0.97). Conclusions: Greater total activity is associated with lower all-cause mortality risk. Replacing sedentary time with light activity or MVPA may reduce mortality risk for older adults.
C1 [Fishman, Ezra I.] Univ Penn, Ctr Populat Studies, 239 McNeil Bldg,3718 Locust Walk, Philadelphia, PA 19104 USA.
[Steeves, Jeremy A.] Maryville Coll, Div Educ, Maryville, TN USA.
[Zipunnikov, Vadim] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD USA.
[Koster, Annemarie] Maastricht Univ, Dept Social Med, NL-6200 MD Maastricht, Netherlands.
[Berrigan, David] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Harris, Tamara A.] NIA, Lab Epidemiol & Populat Sci, Bethesda, MD 20892 USA.
[Murphy, Rachel] Univ British Columbia, Fac Med, Vancouver, BC, Canada.
RP Fishman, EI (reprint author), Univ Penn, Ctr Populat Studies, 239 McNeil Bldg,3718 Locust Walk, Philadelphia, PA 19104 USA.
EM fishmane@sas.upenn.edu
RI Koster, Annemarie/E-7438-2010
FU National Institute on Aging, National Institutes of Health; National
Institute on Aging [R01AG040212]
FX This work was supported by the Intramural Research Program at the
National Institute on Aging, National Institutes of Health, and by the
National Institute on Aging (grant no. R01AG040212).
NR 40
TC 5
Z9 5
U1 1
U2 6
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0195-9131
EI 1530-0315
J9 MED SCI SPORT EXER
JI Med. Sci. Sports Exerc.
PD JUL
PY 2016
VL 48
IS 7
BP 1303
EP 1311
DI 10.1249/MSS.0000000000000885
PG 9
WC Sport Sciences
SC Sport Sciences
GA DO9CQ
UT WOS:000378082300011
PM 26848889
ER
PT J
AU Kumar, A
Leinisch, F
Kadiiska, MB
Corbett, J
Mason, RP
AF Kumar, Ashutosh
Leinisch, Fabian
Kadiiska, Maria B.
Corbett, Jean
Mason, Ronald P.
TI Formation and Implications of Alpha-Synuclein Radical in Maneb- and
Paraquat-Induced Models of Parkinson's Disease
SO MOLECULAR NEUROBIOLOGY
LA English
DT Article
DE Protein radicals; Peroxynitrite; Parkinson's disease; Immuno-spin
trapping; DMPO
ID NITRIC-OXIDE; DOPAMINERGIC NEUROTOXICITY; SUPEROXIDE-DISMUTASE; PROTEIN
RADICALS; NADPH OXIDASE; IN-VIVO; 2 PARTS; PEROXYNITRITE; NITRATION;
INACTIVATION
AB Parkinson's disease (PD) is a debilitating, progressive, neurodegenerative disorder characterized by progressive loss of dopaminergic neurons and motor deficits. Alpha-synuclein-containing aggregates represent a feature of a variety of neurodegenerative disorders, including PD; however, the mechanism that initiates and promotes intraneuronal alpha-synuclein aggregation remains unknown. We hypothesized protein radical formation as an initiating mechanism for alpha-synuclein aggregation. Therefore, we used the highly sensitive immuno-spin trapping technique to investigate protein radical formation as a possible mechanism of alpha-synuclein aggregation as well as to investigate the source of protein radical formation in the midbrains of Maneb- and paraquat-coexposed mice. Coexposure to Maneb and paraquat for 6 weeks resulted in active microgliosis, NADPH oxidase activation, and inducible nitric oxide synthase (iNOS) induction, which culminated in protein radical formation in the midbrains of mice. Results obtained with immuno-spin trapping and immunoprecipitation experiments confirmed formation of alpha-synuclein radicals in dopaminergic neurons of exposed mice. Free radical formation requires NADPH oxidase and iNOS, as indicated by decreased protein radical formation in knockout mice (P47phox(-/-) and iNOS(-/-)) and in mice treated with inhibitors such as FeTPPS (a peroxynitrite decomposition catalyst), 1400 W (an iNOS inhibitor), or apocynin (a NADPH oxidase inhibitor). Concurrence of protein radical formation with dopaminergic neuronal death indicated a link between protein radicals and disease progression. Taken together, these results show for the first time the formation and detection of the alpha-synuclein radical and suggest that NADPH oxidase and iNOS play roles in peroxynitrite-mediated protein radical formation and subsequent neuronal death in the midbrains of Maneb- and paraquat-coexposed mice.
C1 [Kumar, Ashutosh; Leinisch, Fabian; Kadiiska, Maria B.; Corbett, Jean; Mason, Ronald P.] NIEHS, Free Radical Metab Grp, Immun Inflammat & Dis Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.
RP Kumar, A (reprint author), NIEHS, Free Radical Metab Grp, Immun Inflammat & Dis Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.
EM kumara10@niehs.nih.gov
FU National Institutes of Health; National Institute of Environmental
Health Sciences
FX The authors gratefully acknowledge Dr. Ann Motten and Mary Mason for
their valuable help in the preparation of the manuscript. We are very
thankful to Dr. Thomas van't Erve and Dr. Birandra Sinha for reviewing
the manuscript. This work has been supported by the Intramural Research
Program of the National Institutes of Health and the National Institute
of Environmental Health Sciences.
NR 45
TC 2
Z9 2
U1 6
U2 12
PU HUMANA PRESS INC
PI TOTOWA
PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA
SN 0893-7648
EI 1559-1182
J9 MOL NEUROBIOL
JI Mol. Neurobiol.
PD JUL
PY 2016
VL 53
IS 5
BP 2983
EP 2994
DI 10.1007/s12035-015-9179-1
PG 12
WC Neurosciences
SC Neurosciences & Neurology
GA DO7AU
UT WOS:000377935400024
PM 25952542
ER
PT J
AU Murase, S
Lantz, CL
Kim, E
Gupta, N
Higgins, R
Stopfer, M
Hoffman, DA
Quinlan, EM
AF Murase, Sachiko
Lantz, Crystal L.
Kim, Eunyoung
Gupta, Nitin
Higgins, Richard
Stopfer, Mark
Hoffman, Dax A.
Quinlan, Elizabeth M.
TI Matrix Metalloproteinase-9 Regulates Neuronal Circuit Development and
Excitability
SO MOLECULAR NEUROBIOLOGY
LA English
DT Article
DE Extracellular matrix; Cell death; Dendritic morphology; Spontaneous
activity; Kainate-induced seizure
ID TEMPORAL-LOBE EPILEPSY; LONG-TERM POTENTIATION; CA1 PYRAMIDAL NEURONS;
OCCURRING CELL-DEATH; FRAGILE-X-SYNDROME; MATRIX METALLOPROTEINASES;
HIPPOCAMPAL-NEURONS; EXTRACELLULAR-MATRIX; NEWBORN HIPPOCAMPUS; SYNAPTIC
PLASTICITY
AB In early postnatal development, naturally occurring cell death, dendritic outgrowth, and synaptogenesis sculpt neuronal ensembles into functional neuronal circuits. Here, we demonstrate that deletion of the extracellular proteinase matrix metalloproteinase-9 (MMP-9) affects each of these processes, resulting in maladapted neuronal circuitry. MMP-9 deletion increases the number of CA1 pyramidal neurons but decreases dendritic length and complexity. Parallel changes in neuronal morphology are observed in primary visual cortex and persist into adulthood. Individual CA1 neurons in MMP-9(-/-) mice have enhanced input resistance and a significant increase in the frequency, but not amplitude, of miniature excitatory postsynaptic currents (mEPSCs). Additionally, deletion of MMP-9 significantly increases spontaneous neuronal activity in awake MMP-9(-/-) mice and enhances response to acute challenge by the excitotoxin kainate. Our data document a novel role for MMP-9-dependent proteolysis: the regulation of several aspects of circuit maturation to constrain excitability throughout life.
C1 [Murase, Sachiko] NINDS, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
[Murase, Sachiko; Lantz, Crystal L.; Higgins, Richard; Quinlan, Elizabeth M.] Univ Maryland, Dept Biol, College Pk, MD 20742 USA.
[Murase, Sachiko; Lantz, Crystal L.; Higgins, Richard; Quinlan, Elizabeth M.] Univ Maryland, Neurosci & Cognit Sci Program, College Pk, MD 20742 USA.
[Kim, Eunyoung; Hoffman, Dax A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Mol Neurophysiol & Biophys Sect, Program Dev Neurosci, NIH, Bethesda, MD 20892 USA.
[Gupta, Nitin; Stopfer, Mark] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Lab Cellular & Synapt Neurophysiol, NIH, Bethesda, MD 20892 USA.
RP Murase, S (reprint author), NINDS, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.; Murase, S (reprint author), Univ Maryland, Dept Biol, College Pk, MD 20742 USA.; Murase, S (reprint author), Univ Maryland, Neurosci & Cognit Sci Program, College Pk, MD 20742 USA.
EM smurase@umd.edu
OI Gupta, Nitin/0000-0002-8408-3848; Hoffman, Dax/0000-0001-6999-2157
FU NIH; NICHD; NINDS; [R01EY016431]
FX This work was supported by the Intramural Research Program of the NIH,
NICHD and NINDS, and R01EY016431 to EMQ.
NR 75
TC 3
Z9 3
U1 2
U2 7
PU HUMANA PRESS INC
PI TOTOWA
PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA
SN 0893-7648
EI 1559-1182
J9 MOL NEUROBIOL
JI Mol. Neurobiol.
PD JUL
PY 2016
VL 53
IS 5
BP 3477
EP 3493
DI 10.1007/s12035-015-9295-y
PG 17
WC Neurosciences
SC Neurosciences & Neurology
GA DO7AU
UT WOS:000377935400065
PM 26093382
ER
PT J
AU Filardy, AA
He, J
Bennink, J
Yewdell, J
Kelsall, BL
AF Filardy, A. A.
He, J.
Bennink, J.
Yewdell, J.
Kelsall, B. L.
TI Posttranscriptional control of NLRP3 inflammasome activation in colonic
macrophages
SO MUCOSAL IMMUNOLOGY
LA English
DT Article
ID CHRONIC INTESTINAL INFLAMMATION; REGULATORY T-CELLS; INTERLEUKIN-10
RECEPTOR; BOWEL-DISEASE; PROTEASOME INHIBITORS; DENDRITIC CELLS;
LY6C(HI) MONOCYTES; CROHNS-DISEASE; IN-VIVO; EXPRESSION
AB Colonic macrophages (cMPs) are important for intestinal homeostasis as they kill microbes and yet produce regulatory cytokines. Activity of the NLRP3 (nucleotide-binding leucine-rich repeat-containing pyrin receptor 3) inflammasome, a major sensor of stress and microorganisms that results in pro-inflammatory cytokine production and cell death, must be tightly controlled in the intestine. We demonstrate that resident cMPs are hyporesponsive to NLRP3 inflammasome activation owing to a remarkable level of posttranscriptional control of NLRP3 and pro-interleukin-1 beta (proIL-1 beta) protein expression, which was also seen for tumor necrosis factor-alpha and IL-6, but lost during experimental colitis. Resident cMPs rapidly degraded NLRP3 and proIL-1 beta proteins by the ubiquitin/proteasome system. Finally, blocking IL-10R-signaling in vivo enhanced NLRP3 and proIL-1 beta protein but not mRNA levels in resident cMPs, implicating a role for IL-10 in environmental conditioning of cMPs. These data are the first to show dramatic posttranscriptional control of inflammatory cytokine production by a relevant tissue-derived macrophage population and proteasomal degradation of proIL-1 beta and NLRP3 as a mechanism to control inflammasome activation, findings which have broad implications for our understanding of intestinal and systemic inflammatory diseases.
C1 [Filardy, A. A.; He, J.; Kelsall, B. L.] NIAID, Mucosal Immunobiol Sect, Lab Mol Immunol, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Bennink, J.; Yewdell, J.] NIAID, Cellular Biol Sect, Viral Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Bennink, J.; Yewdell, J.] NIAID, Viral Immunol Sect, Viral Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
RP Kelsall, BL (reprint author), NIAID, Mucosal Immunobiol Sect, Lab Mol Immunol, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM bkelsall@niaid.nih.gov
FU Division of Intramural Research, NIAID, NIH; Brazilian National Council
for Scientific and Technological Development/Science Without Borders
Program (CNPq/CsF) postdoctoral fellowship
FX This work was supported by the Division of Intramural Research, NIAID,
NIH. A.A.F. was a recipient of the Brazilian National Council for
Scientific and Technological Development/Science Without Borders Program
(CNPq/CsF) postdoctoral fellowship. We thank Alan Sher, Dan Barber,
Dragana Jankovic, and Katrin Meyer-Barber for their helpful discussion,
Elina Stregevsky from NIAID FACS sorting facility, and the members of
the NIAID Comparative Medicine Branch animal facilities for technical
assistance.
NR 42
TC 4
Z9 4
U1 2
U2 4
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1933-0219
EI 1935-3456
J9 MUCOSAL IMMUNOL
JI Mucosal Immunol.
PD JUL
PY 2016
VL 9
IS 4
BP 850
EP 858
DI 10.1038/mi.2015.109
PG 9
WC Immunology
SC Immunology
GA DP2TW
UT WOS:000378346800002
PM 26627461
ER
PT J
AU Veenbergen, S
van Berkel, LA
du Pre, MF
He, J
Karrich, JJ
Costes, LMM
Luk, F
Simons-Oosterhuis, Y
Raatgeep, HC
Cerovic, V
Cupedo, T
Mowat, AM
Kelsall, BL
Samsom, JN
AF Veenbergen, S.
van Berkel, L. A.
du Pre, M. F.
He, J.
Karrich, J. J.
Costes, L. M. M.
Luk, F.
Simons-Oosterhuis, Y.
Raatgeep, H. C.
Cerovic, V.
Cupedo, T.
Mowat, A. M.
Kelsall, B. L.
Samsom, J. N.
TI Colonic tolerance develops in the iliac lymph nodes and can be
established independent of CD103(+) dendritic cells
SO MUCOSAL IMMUNOLOGY
LA English
DT Article
ID REGULATORY T-CELLS; INTESTINAL IMMUNE-SYSTEM; RETINOIC-ACID; INTEGRIN
ALPHA-V-BETA-8; ORAL TOLERANCE; IN-VIVO; ANTIGEN; GENERATION;
DIFFERENTIATION; HOMEOSTASIS
AB Tolerance to harmless exogenous antigens is the default immune response in the gastrointestinal tract. Although extensive studies have demonstrated the importance of the mesenteric lymph nodes (MLNs) and intestinal CD103(+) dendritic cells (DCs) in driving small intestinal tolerance to protein antigen, the structural and immunological basis of colonic tolerance remain poorly understood. We show here that the caudal and iliac lymph nodes (ILNs) are inductive sites for distal colonic immune responses and that colonic T cell-mediated tolerance induction to protein antigen is initiated in these draining lymph nodes and not in MLNs. In agreement, colonic tolerance induction was not altered by mesenteric lymphadenectomy. Despite tolerance development, CD103(-)CD11b(+) DCs, which are the major migratory DC population in the MLNs, and the tolerance-related retinoic acid-generating enzyme RALDH2 were virtually absent from the ILNs. Administration of ovalbumin (OVA) to the distal colon did increase the number of CD11c(+)MHCII(hi) migratory CD103(-)CD11b(+) DCs and CD103(-)CD11b(+) DCs in the ILNs. Strikingly, colonic tolerance was intact in Batf3-deficient mice specifically lacking CD103(-)CD11b(+) DCs, suggesting that CD103(-) DCs in the ILNs are sufficient to drive tolerance induction after protein antigen encounter in the distal colon. Altogether, we identify different inductive sites for small intestinal and colonic T-cell responses and reveal that distinct cellular mechanisms are operative to maintain tolerance at these sites.
C1 [Veenbergen, S.; van Berkel, L. A.; du Pre, M. F.; Costes, L. M. M.; Luk, F.; Simons-Oosterhuis, Y.; Raatgeep, H. C.; Samsom, J. N.] Erasmus Univ, Med Ctr, Div Gastroenterol & Nutr, Pediat Lab, Rotterdam, Netherlands.
[He, J.; Kelsall, B. L.] NIAID, Mucosal Immunobiol Sect, Lab Mol Immunol, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Karrich, J. J.; Cupedo, T.] Erasmus Univ, Med Ctr, Dept Hematol, Rotterdam, Netherlands.
[Cerovic, V.] Rhein Westfal TH Aachen, Inst Mol Med, D-52062 Aachen, Germany.
[Mowat, A. M.] Univ Glasgow, Inst Infect Immun & Inflammat, Ctr Immunobiol, Glasgow, Lanark, Scotland.
RP Samsom, JN (reprint author), Erasmus Univ, Med Ctr, Div Gastroenterol & Nutr, Pediat Lab, Rotterdam, Netherlands.
EM j.samsom@erasmusmc.nl
FU Dutch Digestive Foundation [WO 10-37]; Sophia Foundation [470]
FX We gratefully acknowledge E. Stregevsky from the National Institute of
Allergy and Infectious Diseases (NIAID) sorting facility, I. Hekking, M.
Muijtjens, E. Fijneman from the ErasmusMC SkillsLab, and the animal
caretakers at the Erasmus University Medical Center Rotterdam. This work
was supported by the Dutch Digestive Foundation grant (WO 10-37) and
Sophia Foundation grant 470.
NR 46
TC 0
Z9 0
U1 3
U2 4
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1933-0219
EI 1935-3456
J9 MUCOSAL IMMUNOL
JI Mucosal Immunol.
PD JUL
PY 2016
VL 9
IS 4
BP 894
EP 906
DI 10.1038/mi.2015.118
PG 13
WC Immunology
SC Immunology
GA DP2TW
UT WOS:000378346800006
PM 26577569
ER
PT J
AU Jung, Y
Hsieh, LS
Lee, AM
Zhou, ZF
Coman, D
Heath, CJ
Hyder, F
Mineur, YS
Yuan, QP
Goldman, D
Bordey, A
Picciotto, MR
AF Jung, Yonwoo
Hsieh, Lawrence S.
Lee, Angela M.
Zhou, Zhifeng
Coman, Daniel
Heath, Christopher J.
Hyder, Fahmeed
Mineur, Yann S.
Yuan, Qiaoping
Goldman, David
Bordey, Angelique
Picciotto, Marina R.
TI An epigenetic mechanism mediates developmental nicotine effects on
neuronal structure and behavior
SO NATURE NEUROSCIENCE
LA English
DT Article
ID TRITHORAX GROUP PROTEIN; FETAL AUDITORY-CORTEX; ACETYLCHOLINE-RECEPTORS;
TRANSCRIPTION FACTOR; PRENATAL NICOTINE; EXPOSURE; MEF2; DROSOPHILA;
GENES; DIFFERENTIATION
AB Developmental nicotine exposure causes persistent changes in cortical neuron morphology and in behavior. We used microarray screening to identify master transcriptional or epigenetic regulators mediating these effects of nicotine and discovered increases in Ash2I mRNA, encoding a component of a histone methyltransferase complex. We therefore examined genome-wide changes in trimethylation of histone H3 on Lys4 (H3K4me3), a mark induced by the Ash2I complex associated with increased gene transcription. A large proportion of regulated promoter sites were involved in synapse maintenance. We found that Mef2c interacts with Ash2I and mediates changes in H3K4me3. Knockdown of Ash2I or Mef2c abolished nicotine-mediated alterations of dendritic complexity in vitro and in vivo, and attenuated nicotine-dependent changes in passive avoidance behavior. In contrast, overexpression mimicked nicotine-mediated alterations of neuronal structure and passive avoidance behavior. These studies identify Ash2I as a target induced by nicotinic stimulation that couples developmental nicotine exposure to changes in brain epigenetic marks, neuronal structure and behavior.
C1 [Jung, Yonwoo; Lee, Angela M.; Heath, Christopher J.; Mineur, Yann S.; Picciotto, Marina R.] Yale Univ, Sch Med, Div Mol Psychiat, New Haven, CT USA.
[Jung, Yonwoo; Lee, Angela M.; Heath, Christopher J.; Picciotto, Marina R.] Yale Univ, Sch Med, Interdept Neurosci Program, New Haven, CT USA.
[Hsieh, Lawrence S.; Bordey, Angelique] Yale Univ, Sch Med, Dept Neurosurg, New Haven, CT USA.
[Hsieh, Lawrence S.; Bordey, Angelique] Yale Univ, Sch Med, Dept Cellular & Mol Physiol, New Haven, CT 06510 USA.
[Zhou, Zhifeng; Yuan, Qiaoping; Goldman, David] NIAAA, Neurogenet Lab, NIH, Rockville, MD 20852 USA.
[Coman, Daniel; Hyder, Fahmeed] Yale Univ, Sch Med, Dept Radiol, New Haven, CT 06510 USA.
[Coman, Daniel; Hyder, Fahmeed] Yale Univ, Sch Med, Biomed Imaging Magnet Resonance Res Ctr, New Haven, CT USA.
[Coman, Daniel; Hyder, Fahmeed] Yale Univ, Sch Med, Magnet Resonance Res Ctr, New Haven, CT USA.
[Heath, Christopher J.] Open Univ, Dept Life Hlth & Chem Sci, Milton Keynes MK7 6AA, Bucks, England.
[Hyder, Fahmeed] Yale Univ, Sch Appl Sci & Engn, Dept Biomed Engn, New Haven, CT USA.
RP Picciotto, MR (reprint author), Yale Univ, Sch Med, Div Mol Psychiat, New Haven, CT USA.; Picciotto, MR (reprint author), Yale Univ, Sch Med, Interdept Neurosci Program, New Haven, CT USA.
EM marina.picciotto@yale.edu
RI Goldman, David/F-9772-2010
OI Goldman, David/0000-0002-1724-5405
FU National Institutes of Health [DA14241, DA10455, NS052519, NS086329];
State of Connecticut; Department of Mental Health and Addiction
Services; Kavli Institute for Neuroscience at Yale
FX This work was supported by grants DA14241 (M.R.P.), DA10455 (M.R.P.),
NS052519 (RH.) and NS086329 (EH.) from the National Institutes of
Health, the State of Connecticut, Department of Mental Health and
Addiction Services and the Kavli Institute for Neuroscience at Yale.
NR 43
TC 4
Z9 4
U1 5
U2 6
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1097-6256
EI 1546-1726
J9 NAT NEUROSCI
JI Nat. Neurosci.
PD JUL
PY 2016
VL 19
IS 7
BP 905
EP 914
DI 10.1038/nn.4315
PG 10
WC Neurosciences
SC Neurosciences & Neurology
GA DP8PH
UT WOS:000378759600009
PM 27239938
ER
PT J
AU Gupta, S
Kaplan, MJ
AF Gupta, Sarthak
Kaplan, Mariana J.
TI The role of neutrophils and NETosis in autoimmune and renal diseases
SO NATURE REVIEWS NEPHROLOGY
LA English
DT Review
ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; PEPTIDYLARGININE DEIMINASE INHIBITION;
ANCA-ASSOCIATED VASCULITIS; CYTOPLASMIC ANTIBODY VASCULITIS;
EXTRACELLULAR TRAP FORMATION; ARTHRITIS SYNOVIAL-FLUID; SMALL-VESSEL
VASCULITIS; T-CELL RESPONSES; RHEUMATOID-ARTHRITIS; ANTIPHOSPHOLIPID
SYNDROME
AB Systemic autoimmune diseases are a group of disorders characterized by a failure in self-tolerance to a wide variety of autoantigens. In genetically predisposed individuals, these diseases occur as a multistep process in which environmental factors have key roles in the development of abnormal innate and adaptive immune responses. Experimental evidence collected in the past decade suggests that neutrophils-the most abundant type of white blood cell-might have an important role in the pathogenesis of these diseases by contributing to the initiation and perpetuation of immune dysregulation through the formation of neutrophil extracellular traps (NETs), synthesis of proinflammatory cytokines and direct tissue damage. Many of the molecules externalized through NET formation are considered to be key autoantigens and might be involved in the generation of autoimmune responses in predisposed individuals. In several systemic autoimmune diseases, the imbalance between NET formation and degradation might increase the half-life of these lattices, which could enhance the exposure of the immune system to modified autoantigens and increase the capacity for NET-induced organ damage. This Review details the role of neutrophils and NETs in the pathophysiology of systemic autoimmune diseases, including their effect on renal damage, and discusses neutrophil targets as potential novel therapies for these diseases.
C1 [Gupta, Sarthak; Kaplan, Mariana J.] NIAMSD, System Autoimmun Branch, Intramural Res Program, NIH, Room 6D 47C,10 Ctr Dr, Bethesda, MD 20892 USA.
RP Kaplan, MJ (reprint author), NIAMSD, System Autoimmun Branch, Intramural Res Program, NIH, Room 6D 47C,10 Ctr Dr, Bethesda, MD 20892 USA.
EM mariana.kaplan@nih.gov
NR 163
TC 3
Z9 3
U1 3
U2 9
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1759-5061
EI 1759-507X
J9 NAT REV NEPHROL
JI Nat. Rev. Nephrol.
PD JUL
PY 2016
VL 12
IS 7
BP 402
EP 413
DI 10.1038/nrneph.2016.71
PG 12
WC Urology & Nephrology
SC Urology & Nephrology
GA DO9EU
UT WOS:000378088100004
PM 27241241
ER
PT J
AU Bilgel, M
Prince, JL
Wong, DF
Resnick, SM
Jedynak, BM
AF Bilgel, Murat
Prince, Jerry L.
Wong, Dean F.
Resnick, Susan M.
Jedynak, Bruno M.
TI A multivariate nonlinear mixed effects model for longitudinal image
analysis: Application to amyloid imaging
SO NEUROIMAGE
LA English
DT Article
DE Longitudinal image analysis; Progression score; Amyloid imaging
ID PRECLINICAL ALZHEIMERS-DISEASE; MILD COGNITIVE IMPAIRMENT; BIOMARKER
CHANGES; BETA DEPOSITION; PROGRESSION; BRAIN; REGISTRATION;
TRAJECTORIES; ROBUST; COHORT
AB It is important to characterize the temporal trajectories of disease-related biomarkers in order to monitor progression and identify potential points of intervention. These are especially important for neurodegenerative diseases, as therapeutic intervention is most likely to be effective in the preclinical disease stages prior to significant neuronal damage. Neuroimaging allows for the measurement of structural, functional, and metabolic integrity of the brain at the level of voxels, whose volumes are on the order of mm(3). These voxelwise measurements provide a rich collection of disease indicators. Longitudinal neuroimaging studies enable the analysis of changes in these voxelwise measures. However, commonly used longitudinal analysis approaches, such as linear mixed effects models, do not account for the fact that individuals enter a study at various disease stages and progress at different rates, and generally consider each voxelwise measure independently. We propose a multivariate nonlinear mixed effects model for estimating the trajectories of voxelwise neuroimaging biomarkers from longitudinal data that accounts for such differences across individuals. The method involves the prediction of a progression score for each visit based on a collective analysis of voxelwise biomarker data within an expectation-maximization framework that efficiently handles large amounts of measurements and variable number of visits per individual, and accounts for spatial correlations among voxels. This score allows individuals with similar progressions to be aligned and analyzed together, which enables the construction of a trajectory of brain changes as a function of an underlying progression or disease stage. We apply our method to studying cortical beta-amyloid deposition, a hallmark of preclinical Alzheimer's disease, as measured using positron emission tomography. Results on 104 individuals with a total of 300 visits suggest that precuneus is the earliest cortical region to accumulate amyloid, closely followed by the cingulate and frontal cortices, then by the lateral parietal cortex. The extracted progression scores reveal a pattern similar to mean cortical distribution volume ratio (DVR), an index of global brain amyloid levels. The proposed method can be applied to other types of longitudinal imaging data, including metabolism, blood flow, tau, and structural imaging-derived measures, to extract individualized summary scores indicating disease progression and to provide voxelwise trajectories that can be compared between brain regions. Published by Elsevier Inc.
C1 [Bilgel, Murat; Prince, Jerry L.] Johns Hopkins Univ, Sch Engn, Image Anal & Commun Lab, Baltimore, MD USA.
[Bilgel, Murat; Prince, Jerry L.] Johns Hopkins Univ, Sch Med, Dept Biomed Engn, Baltimore, MD 21205 USA.
[Bilgel, Murat; Resnick, Susan M.] NIA, Lab Behav Neurosci, NIH, Baltimore, MD 21224 USA.
[Prince, Jerry L.] Johns Hopkins Univ, Dept Elect & Comp Engn, Sch Engn, Baltimore, MD 21218 USA.
[Prince, Jerry L.; Wong, Dean F.] Johns Hopkins Univ, Sch Med, Dept Radiol, Baltimore, MD 21205 USA.
[Jedynak, Bruno M.] Portland State Univ, Dept Math & Stat, Portland, OR 97207 USA.
RP Bilgel, M (reprint author), NIA, Lab Behav Neurosci, 251 Bayview Blvd,Suite 100,Rm 04B316, Baltimore, MD 21224 USA.
EM murat.bilgel@nih.gov
OI Bilgel, Murat/0000-0001-5042-7422
FU Intramural Research Program of National Institutes of Health; Michael J.
Fox Foundation for Parkinson's Research [9310]
FX We thank Kalyani Kansal for her thorough review of the mathematical
derivations and assistance with code testing. This research was
supported in part by the Intramural Research Program of the National
Institutes of Health and by the Michael J. Fox Foundation for
Parkinson's Research, MJFF Research Grant ID: 9310.
NR 45
TC 0
Z9 0
U1 2
U2 6
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1053-8119
EI 1095-9572
J9 NEUROIMAGE
JI Neuroimage
PD JUL 1
PY 2016
VL 134
BP 658
EP 670
DI 10.1016/j.neuroimage.2016.04.001
PG 13
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA DO8PP
UT WOS:000378045900061
PM 27095307
ER
PT J
AU Fisher, DE
Jonasson, F
Klein, R
Jonsson, PV
Eiriksdottir, G
Launer, LJ
Gudnason, V
Cotch, MF
AF Fisher, Diana E.
Jonasson, Fridbert
Klein, Ronald
Jonsson, Palmi V.
Eiriksdottir, Gudny
Launer, Lenore J.
Gudnason, Vilmundur
Cotch, Mary Frances
TI Mortality in Older Persons with Retinopathy and Concomitant Health
Conditions The Age, Gene/Environment Susceptibility-Reykjavik Study
SO OPHTHALMOLOGY
LA English
DT Article
ID CORONARY-HEART-DISEASE; CHRONIC KIDNEY-DISEASE; ALL-CAUSE MORTALITY;
RETINAL MICROVASCULAR ABNORMALITIES; CARDIOVASCULAR-DISEASE;
DIABETIC-RETINOPATHY; HYPERTENSIVE RETINOPATHY; RISK-FACTORS;
POPULATION; COHORT
AB Purpose: To assess the impact of retinopathy on mortality in older persons with concomitant health conditions.
Design: Population-based prospective cohort study.
Participants: A total of 4966 individuals aged 67 to 96 years (43.2% were male) from the Age, Gene/Environment Susceptibility-Reykjavik Study (AGES-RS).
Methods: Retinopathy was evaluated from digital fundus images (2002-2006) using the modified Airlie House adaptation of the Early Treatment Diabetic Retinopathy Study protocol. Mortality was assessed through September 2013 (cause of death assigned through 2009). Cox proportional hazards regression models, with age as the time scale, estimated the association between retinopathy and death while controlling for risk factors and the presence of concomitant health conditions.
Main Outcome Measures: Mortality from all causes and cardiovascular disease (CVD).
Results: Among the 4966 participants, 503 (10.1%) had diabetes and 614 (12.4%) had retinopathy at baseline. A subset of these (136 [2.7%]) had both diabetes and retinopathy. After a median follow-up of 8.6 years, 1763 persons died, 276 (45.0%) with retinopathy and 1487 (34.2%) without retinopathy, of whom 76 and 162 persons, respectively, also had diabetes. There were 366 deaths from CVD through 2009, 72 (11.7%) in persons with retinopathy and 294 (6.8%) in those without retinopathy. In multivariable analyses, retinopathy was significantly associated with all-cause mortality (hazard ratio [HR], 1.26; 95% confidence interval [CI], 1.10-1.43; P < 0.01) and CVD-related mortality (HR, 1.57; 95% CI, 1.20-2.06; P < 0.01). Findings were more striking in men: all-cause HR, 1.33 (95% CI, 1.11-1.60) and CVD HR, 1.81 (95% CI, 1.25-2.63). Risk of mortality was further increased among those with retinopathy concomitant with microalbuminuria (all-cause HR, 1.70; 95% CI, 1.03-2.23, and CVD HR, 2.04; 95% CI, 1.27-3.28) and those with retinopathy, microalbuminuria, and diabetes (all-cause HR, 2.01; 95% CI, 1.22-3.31, and CVD HR, 5.24; 95% CI, 1.91-14.42). History of clinical stroke increased the risk of CVD-related mortality among persons with retinopathy (HR, 3.30; 95% CI, 2.05-5.32), particularly those with retinopathy and diabetes (HR, 5.38; 95% CI, 1.80-16.06).
Conclusions: Even minimal retinopathy was a significant predictor of increased mortality in older persons, particularly men, irrespective of diabetes status. Persons with retinopathy may warrant closer clinical management of general health. (C) 2016 Published by Elsevier on behalf of the American Academy of Ophthalmology.
C1 [Fisher, Diana E.; Cotch, Mary Frances] NEI, Div Epidemiol & Clin Applicat, Intramural Res Program, NIH, Bldg 10-CRC,Room 3-2521, Bethesda, MD 20892 USA.
[Jonasson, Fridbert; Jonsson, Palmi V.; Gudnason, Vilmundur] Univ Iceland, Fac Med, Reykjavik, Iceland.
[Jonasson, Fridbert] Landspitali Univ Hosp, Dept Ophthalmol, Reykjavik, Iceland.
[Klein, Ronald] Univ Wisconsin, Ophthalmol & Visual Sci, Madison, WI USA.
[Jonsson, Palmi V.] Landspitali Univ Hosp, Dept Geriatr, Reykjavik, Iceland.
[Eiriksdottir, Gudny; Gudnason, Vilmundur] Iceland Heart Assoc, Kopavogur, Iceland.
[Launer, Lenore J.] NIA, Lab Epidemiol & Populat Sci, Intramural Res Program, NIH, Bethesda, MD 20892 USA.
RP Fisher, DE (reprint author), NEI, Div Epidemiol & Clin Applicat, Intramural Res Program, NIH, Bldg 10-CRC,Room 3-2521, Bethesda, MD 20892 USA.
EM diana.fisher@nih.gov
FU National Institutes of Health (Intramural Research Programs of the
National Institute of Aging and the National Eye Institute)
[ZIAEY00401]; National Institutes of Health [N01-AG-1-2100]; IHA;
Icelandic Parliament; Helga Jonsdottir and Sigurlidi Kristjansson
Research Fund; University of Iceland Research Fund
FX Supported by the National Institutes of Health (Intramural Research
Programs of the National Institute of Aging and the National Eye
Institute, ZIAEY00401), National Institutes of Health Contract Number
N01-AG-1-2100, the IHA, the Icelandic Parliament, the University of
Iceland Research Fund, and the Helga Jonsdottir and Sigurlidi
Kristjansson Research Fund. The funders had no role in data collection,
management, analysis, and interpretation of the data, preparation,
writing, and approval of the manuscript, and decision to submit the
manuscript for publication.
NR 38
TC 0
Z9 0
U1 2
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0161-6420
EI 1549-4713
J9 OPHTHALMOLOGY
JI Ophthalmology
PD JUL
PY 2016
VL 123
IS 7
BP 1570
EP 1580
DI 10.1016/j.ophtha.2016.02.045
PG 11
WC Ophthalmology
SC Ophthalmology
GA DP3KC
UT WOS:000378391100029
PM 27067925
ER
PT J
AU Gibbins, KJ
Silver, RM
Pinar, H
Reddy, UM
Parker, CB
Thorsten, V
Willinger, M
Dudley, DJ
Bukowski, R
Saade, GR
Koch, MA
Conway, D
Hogue, CJ
Stoll, BJ
Goldenberg, RL
AF Gibbins, Karen J.
Silver, Robert M.
Pinar, Halit
Reddy, Uma M.
Parker, Corette B.
Thorsten, Vanessa
Willinger, Marian
Dudley, Donald J.
Bukowski, Radek
Saade, George R.
Koch, Matthew A.
Conway, Deborah
Hogue, Carol J.
Stoll, Barbara J.
Goldenberg, Robert L.
TI Stillbirth, hypertensive disorders of pregnancy, and placental pathology
SO PLACENTA
LA English
DT Article
DE Placental pathology; Preeclampsia; Stillbirth
ID LATE-ONSET PREECLAMPSIA; FETAL-GROWTH RESTRICTION; RISK-FACTORS;
MATERNAL UNDERPERFUSION; GESTATIONAL-AGE; UNITED-STATES; LESIONS; DEATH;
SEVERITY; TRENDS
AB Introduction: Stillbirth, preeclampsia, and gestational hypertension (PE/GH) have similar clinical risk factors and redundant placental pathology. We aim to discern if stillbirth with PE/GH has a particular phenotype by comparing stillbirths with and without PE/GH.
Methods: Secondary analysis of the Stillbirth Collaborative Research Network, a population-based cohort study of all stillbirths and a sample of live births from 2006 to 2008 in five catchment areas. We compared placental pathology between stillbirths and with and without PE/GH, stratified by term or preterm. We also compared placental pathology between stillbirths and live births with PE/GH.
Results: 79/518 stillbirths and 140/1200 live births had PE/GH. Amongst preterm stillbirths, there was higher feto-placental ratio in PE/GH pregnancies (OR 1.24 [1.11, 1.37] per unit increase), and there were more parenchymal infarctions (OR 5.77 [3.18, 10.47]). Among PE/GH pregnancies, stillbirths had increased maternal and fetal vascular lesions, including retroplacental hematoma, parenchymal infarction, fibrin deposition, fetal vascular thrombi, and avascular villi.
Discussion: Stillbirth pregnancies are overwhelmingly associated with placental lesions. Parenchymal infarctions are more common in PE/GH preterm stillbirths, but there is significant overlap in lesions found in stillbirths and PE/GH. (C) 2016 Elsevier Ltd. All rights reserved.
C1 [Gibbins, Karen J.; Silver, Robert M.] Univ Utah, Sch Med, Salt Lake City, UT USA.
[Pinar, Halit] Brown Univ, Warren Alpert Med Sch, Providence, RI 02912 USA.
[Reddy, Uma M.; Willinger, Marian; Koch, Matthew A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA.
[Parker, Corette B.; Thorsten, Vanessa] RTI Int, Durham, NC USA.
[Dudley, Donald J.] Univ Virginia, Charlottesville, VA 22903 USA.
[Bukowski, Radek] Yale New Haven Med Ctr, 20 York St, New Haven, CT 06504 USA.
[Saade, George R.] Univ Texas Med Branch, Galveston, TX 77555 USA.
[Conway, Deborah] Univ Texas San Antonio, San Antonio, TX USA.
[Hogue, Carol J.; Stoll, Barbara J.] Emory Univ, Atlanta, GA 30322 USA.
[Goldenberg, Robert L.] Columbia Univ, Sch Med, New York, NY USA.
RP Gibbins, KJ (reprint author), Univ Utah, Hlth Sci Ctr, Dept OB GYN, Div Maternal Fetal Med, Suite 2B200,30 North Med Dr, Salt Lake City, UT 84132 USA.
EM Karen.gibbins@hsc.utah.edu
OI Gibbins, Karen/0000-0002-7431-3451
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development [HD45925, HD45944, HD45952, HD45953, HD45954]
FX Supported by grants (HD45925, HD45944, HD45952, HD45953, HD45954, and
HD45925) from the Eunice Kennedy Shriver National Institute of Child
Health and Human Development.
NR 34
TC 0
Z9 0
U1 2
U2 9
PU W B SAUNDERS CO LTD
PI LONDON
PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND
SN 0143-4004
EI 1532-3102
J9 PLACENTA
JI Placenta
PD JUL
PY 2016
VL 43
BP 61
EP 68
DI 10.1016/j.placenta.2016.04.020
PG 8
WC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology
SC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology
GA DP1VY
UT WOS:000378278700010
PM 27324101
ER
PT J
AU Yadav, BK
Neelavalli, J
Krishnamurthy, U
Szalai, G
Shen, YM
Nayak, NR
Chaiworapongsa, T
Hernandez-Andrade, E
Than, NG
Haacke, EM
Romero, R
AF Yadav, Brijesh Kumar
Neelavalli, Jaladhar
Krishnamurthy, Uday
Szalai, Gabor
Shen, Yimin
Nayak, Nihar R.
Chaiworapongsa, Tinnakorn
Hernandez-Andrade, Edgar
Than, Nandor Gabor
Haacke, E. Mark
Romero, Roberto
TI A longitudinal study of placental perfusion using dynamic contrast
enhanced magnetic resonance imaging in murine pregnancy
SO PLACENTA
LA English
DT Article
DE Labyrinth zone; Junctional zone; Contrast enhanced; Central canal; Mice
ID DCE-MRI DATA; ARTERIAL INPUT FUNCTION; REFERENCE REGION MODEL; MOUSE
PLACENTA; BLOOD-FLOW; FETOPLACENTAL VASCULATURE; JUNCTIONAL ZONE; MICE;
GESTATION; QUANTIFICATION
AB Introduction: To evaluate changes in placental perfusion with advancing gestation in normal murine pregnancy using dynamic contrast enhanced magnetic resonance imaging (DCE-MRI).
Methods: Seven timed-pregnant CD-1 mice underwent DCE-MRI scanning longitudinally on gestational days (GD) 13, 15 and 17. Placentas were segmented into high (HPZ) and low perfusion zones (LPZ) using tissue similarity mapping. Blood perfusion of the respective regions and the whole placenta was quantified using the steepest slope method. The diameter of the maternal central canal (CC) was also measured.
Results: An increase in perfusion was observed between GD13 and GD17 in the overall placenta (p = 0.04) and in the HPZ (p = 0.02). Although perfusion in the LPZ showed a slight increasing trend, it was not significant (p = 0.07). Perfusion, in units of ml/min/100 ml, in the overall placenta and the HPZ was respectively 61.2 +/- 31.2 and 106.2 +/- 56.3 at GD13 (n = 19 placentas); 90.3 +/- 43.7 and 139 +/- 55.4 at GD15 (n = 20); and 104.9 +/- 76.1 and 172.2 +/- 85.6 at GD17 (n = 14). The size of the CC increased with advancing gestation (p < 0.05).
Discussion: Using longitudinal DCE-MRI, the gestational age-dependent perfusion change in the normal murine placenta and in its regional compartments was quantified. In mid and late gestations, placental constituent regions differ significantly in their perfusion rates. The CC diameter also showed increase with advancing gestation, which may be playing an important role toward the gestational age-dependent increase in placental perfusion. (C) 2016 Published by Elsevier Ltd.
C1 [Yadav, Brijesh Kumar; Neelavalli, Jaladhar; Krishnamurthy, Uday; Shen, Yimin; Haacke, E. Mark] Wayne State Univ, Sch Med, Dept Radiol, 4201 St Antoine, Detroit, MI 48201 USA.
[Yadav, Brijesh Kumar; Neelavalli, Jaladhar; Krishnamurthy, Uday; Haacke, E. Mark] Wayne State Univ, Coll Engn, Dept Biomed Engn, Detroit, MI USA.
[Szalai, Gabor; Chaiworapongsa, Tinnakorn; Hernandez-Andrade, Edgar; Than, Nandor Gabor; Romero, Roberto] NICHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD USA.
[Szalai, Gabor; Chaiworapongsa, Tinnakorn; Hernandez-Andrade, Edgar; Than, Nandor Gabor; Romero, Roberto] NICHD, Perinatol Res Branch, NIH, DHHS, Detroit, MI USA.
[Nayak, Nihar R.; Chaiworapongsa, Tinnakorn; Hernandez-Andrade, Edgar; Than, Nandor Gabor] Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA.
[Than, Nandor Gabor] Hungarian Acad Sci, Res Ctr Nat Sci, Inst Enzymol, Lendulet Reprod Res Grp, Budapest, Hungary.
[Romero, Roberto] Univ Michigan, Dept Obstet & Gynecol, Ann Arbor, MI 48109 USA.
[Romero, Roberto] Michigan State Univ, Dept Epidemiol & Biostat, E Lansing, MI 48824 USA.
[Romero, Roberto] Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI USA.
RP Neelavalli, J (reprint author), Wayne State Univ, Sch Med, Dept Radiol, 4201 St Antoine, Detroit, MI 48201 USA.
EM jneelava@med.wayne.edu
FU Perinatology Research Branch, Division of Intramural Research, Eunice
Kennedy Shriver National Institute of Child Health and Human Development
(NICHD), National Institutes of Health (NIH), Department of Health and
Human Services (DHHS); NICHD (NIH, DHHS) [HHSN275201300006C]; Small
Business Technology Transfer (STTR) grant from the National Heart, Lung,
and Blood Institute (NHLBI, NIH, DHHS) [1R42HL112580-01A1]; Wayne State
University's Perinatal Research Initiative; Perinatology Virtual
Discovery Grant (by the W.K. Kellogg Foundation award) [P3018205]
FX This research was supported, in part, by the Perinatology Research
Branch, Division of Intramural Research, Eunice Kennedy Shriver National
Institute of Child Health and Human Development (NICHD), National
Institutes of Health (NIH), Department of Health and Human Services
(DHHS); and, in part, with Federal funds from NICHD (NIH, DHHS) under
Contract No. HHSN275201300006C. The authors are grateful to Dr. Theodore
Price (Perinatology Research Branch), Dr. Lisa J. Brossia-Root, Laura
Lee McIntyre, and all personnel involved in the Division of Laboratory
Animal Resources (Wayne State University). This work was also supported,
in part, by a Small Business Technology Transfer (STTR) grant from the
National Heart, Lung, and Blood Institute (NHLBI, NIH, DHHS;
1R42HL112580-01A1), by Wayne State University's Perinatal Research
Initiative and by the Perinatology Virtual Discovery Grant to J.N. (made
possible by the W.K. Kellogg Foundation award P3018205).
NR 58
TC 0
Z9 0
U1 3
U2 3
PU W B SAUNDERS CO LTD
PI LONDON
PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND
SN 0143-4004
EI 1532-3102
J9 PLACENTA
JI Placenta
PD JUL
PY 2016
VL 43
BP 90
EP 97
DI 10.1016/j.placenta.2015.12.019
PG 8
WC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology
SC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology
GA DP1VY
UT WOS:000378278700015
PM 26947613
ER
PT J
AU Marceau, LD
Welch, LC
Pemberton, VL
Pearson, GD
AF Marceau, Lisa D.
Welch, Lisa C.
Pemberton, Victoria L.
Pearson, Gail D.
TI Educating Parents About Pediatric Research: Children and Clinical
Studies Website Qualitative Evaluation
SO QUALITATIVE HEALTH RESEARCH
LA English
DT Article
DE children; education, patient; health information seeking; qualitative
analysis; research, qualitative methods; technology, use in research;
New England region
ID RANDOMIZED CONTROLLED-TRIALS; INFORMED-CONSENT; ATTITUDES; DECISIONS;
LEUKEMIA; PARTICIPATE; DISTRUST; MEDICINE; MOTHERS; ENROLL
AB A gap in information about pediatric clinical trials exists, and parents remain uncertain about what is involved in research studies involving children. We aimed to understand parent perspectives about pediatric clinical research after viewing the online Children and Clinical Studies (CaCS) program. Using a qualitative descriptive study design, we conducted focus groups with parents and phone interviews with physicians. Three themes emerged providing approaches to improve parent's understanding of clinical research by including strategies where parents (a) hear from parents like themselves to learn about pediatric research, (b) receive general clinical research information to complement study-specific details, and (c) are provided more information about the role of healthy child volunteers. Parents found the website a valuable tool that would help them make a decision about what it means to participate in research. This tool can assist parents, providers, and researchers by connecting general information with study-specific information.
C1 [Marceau, Lisa D.] New England Res Inst, 480 Pleasant St,Suite A100, Watertown, MA 02472 USA.
[Welch, Lisa C.] Tufts Univ, Boston, MA 02111 USA.
[Pemberton, Victoria L.] NHLBI, NIH, Bldg 10, Bethesda, MD 20892 USA.
[Pearson, Gail D.] NHLBI, Div Cardiovasc Sci, NIH, Bldg 10, Bethesda, MD 20892 USA.
[Pearson, Gail D.] NHLBI, Adult & Pediat Cardiac Res Program, NIH, Bldg 10, Bethesda, MD 20892 USA.
RP Marceau, LD (reprint author), New England Res Inst, 480 Pleasant St,Suite A100, Watertown, MA 02472 USA.
EM LMarceau@neriscience.com
FU National Heart, Lung, and Blood Institute (NHLBI) of the National
Institutes of Health (NIH) [U01 HL68270]; Eunice Kennedy Shriver
National Institute of Child Health and Human Development (NICHD); Best
Pharmaceuticals for Children Act (BPCA); National Marfan Foundation
(NMF); National Center for Research Resources (NCRR); Gerber Foundation;
Booz Allen Hamilton; Foundation for the National Institutes of Health;
NIH
FX The authors disclosed receipt of the following financial support for the
research, authorship, and/or publication of this article: This article
was primarily supported by Award Number U01 HL68270 from the National
Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of
Health (NIH). Other support for the Children and Clinical Studies Web
program was provided by the Eunice Kennedy Shriver National Institute of
Child Health and Human Development (NICHD), the Best Pharmaceuticals for
Children Act (BPCA), the National Marfan Foundation (NMF), the National
Center for Research Resources (NCRR), the Gerber Foundation, Booz Allen
Hamilton, and the Foundation for the National Institutes of Health. The
role of the funding sources was financial support for the project and
ensuring study compliance with NIH regulations.
NR 33
TC 0
Z9 0
U1 5
U2 7
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1049-7323
EI 1552-7557
J9 QUAL HEALTH RES
JI Qual. Health Res.
PD JUL
PY 2016
VL 26
IS 8
SI SI
BP 1114
EP 1122
DI 10.1177/1049732315616620
PG 9
WC Information Science & Library Science; Social Sciences,
Interdisciplinary; Social Sciences, Biomedical
SC Information Science & Library Science; Social Sciences - Other Topics;
Biomedical Social Sciences
GA DP3WU
UT WOS:000378427400009
PM 26711142
ER
PT J
AU Markmann, JF
Bartlett, ST
Johnson, P
Korsgren, O
Hering, BJ
Scharp, D
Kay, TWH
Bromberg, J
Odorico, JS
Weir, GC
Bridges, N
Kandaswamy, R
Stock, P
Friend, P
Gotoh, M
Cooper, DKC
Park, CG
O'Connell, PJ
Stabler, C
Matsumoto, S
Ludwig, B
Choudhary, P
Khovatchev, B
Rickels, MR
Sykes, M
Wood, K
Kraemer, K
Hwa, A
Stanley, E
Ricordi, C
Zimmerman, M
Greenstein, J
Montanya, E
Otonkoski, T
AF Markmann, James F.
Bartlett, Stephen T.
Johnson, Paul
Korsgren, Olle
Hering, Bernhard J.
Scharp, David
Kay, Thomas W. H.
Bromberg, Jonathan
Odorico, Jon S.
Weir, Gordon C.
Bridges, Nancy
Kandaswamy, Raja
Stock, Peter
Friend, Peter
Gotoh, Mitsukazu
Cooper, David K. C.
Park, Chung-Gyu
O'Connell, Philip J.
Stabler, Cherie
Matsumoto, Shinichi
Ludwig, Barbara
Choudhary, Pratik
Khovatchev, Boris
Rickels, Michael R.
Sykes, Megan
Wood, Kathryn
Kraemer, Kristy
Hwa, Albert
Stanley, Edward
Ricordi, Camillo
Zimmerman, Mark
Greenstein, Julia
Montanya, Eduard
Otonkoski, Timo
TI Executive Summary of IPITA-TTS Opinion Leaders Report on the Future of
beta-Cell Replacement
SO TRANSPLANTATION
LA English
DT Review
ID PORCINE ISLET XENOTRANSPLANTATION; MEDIATED INFLAMMATORY REACTION;
NONHUMAN-PRIMATES; CYNOMOLOGUS MONKEYS; PIG ISLETS; REVERSAL;
TRANSPLANTATION; SURVIVAL; IMMUNOSUPPRESSION; AUTOIMMUNITY
AB The International Pancreas and Islet Transplant Association (IPITA), in conjunction with the Transplantation Society (TTS), convened a workshop to consider the future of pancreas and islet transplantation in the context of potential competing technologies that are under development, including the artificial pancreas, transplantation tolerance, xenotransplantation, encapsulation, stem cell derived beta cells, beta cell proliferation, and endogenous regeneration. Separate workgroups for each topic and then the collective group reviewed the state of the art, hurdles to application, and proposed research agenda for each therapy that would allow widespread application. Herein we present the executive summary of this workshop that focuses on obstacles to application and the research agenda to overcome them; the full length article with detailed background for each topic is published as an online supplement to Transplantation.
C1 [Markmann, James F.] Massachusetts Gen Hosp, Div Transplantat, Boston, MA 02114 USA.
[Bartlett, Stephen T.; Bromberg, Jonathan] Univ Maryland, Sch Med, Dept Surg, Baltimore, MD 21201 USA.
[Johnson, Paul; Friend, Peter; Wood, Kathryn] Univ Oxford, Nuffield Dept Surg Sci, Oxford, England.
[Johnson, Paul; Friend, Peter; Wood, Kathryn] Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England.
[Korsgren, Olle] Uppsala Univ, Dept Immunol Genet & Pathol, Uppsala, Sweden.
[Hering, Bernhard J.; Kandaswamy, Raja] Univ Minnesota, Dept Surg, Schulze Diabet Inst, Box 242 UMHC, Minneapolis, MN 55455 USA.
[Scharp, David] Prodo Labs LLC, Irvine, CA USA.
[Scharp, David] Scharp Lacy Res Inst, Irvine, CA USA.
[Kay, Thomas W. H.] St Vincents Inst Med Res, 41 Victoria Parade, Fitzroy, Vic 3065, Australia.
[Kay, Thomas W. H.] Univ Melbourne, St Vincents Hosp, Dept Med, Melbourne, Vic 3010, Australia.
[Odorico, Jon S.] Univ Wisconsin, Dept Surg, Sch Med & Publ Hlth, Div Transplantat, Madison, WI USA.
[Weir, Gordon C.] Joslin Diabet Ctr, Boston, MA 02215 USA.
[Weir, Gordon C.] Harvard Univ, Sch Med, Boston, MA USA.
[Bridges, Nancy; Kraemer, Kristy] NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Stock, Peter] Univ San Francisco, Med Ctr, Div Transplantat, San Francisco, CA 94117 USA.
[Gotoh, Mitsukazu] Fukushima Med Univ, Dept Surg, Fukushima, Japan.
[Cooper, David K. C.] Univ Pittsburgh, Thomas E Starzl Transplantat Inst, Pittsburgh, PA USA.
[Park, Chung-Gyu] Seoul Natl Univ, Coll Med, Dept Biomed Sci, Xenotransplantat Res Ctr,Dept Microbiol & Immunol, Seoul, South Korea.
[O'Connell, Philip J.] Univ Sydney, Westmead Hosp, Ctr Transplant & Renal Res, Westmead Millennium Inst, Westmead, NSW 2145, Australia.
[Stabler, Cherie] Univ Florida, Dept Biomed Engn, Gainesville, FL USA.
[Matsumoto, Shinichi] Otsuka Pharmaceut Factory Inc, Naruto, Japan.
[Matsumoto, Shinichi] Natl Ctr Global Hlth & Med, Tokyo, Japan.
[Ludwig, Barbara] Tech Univ Dresden, Dept Med 3, D-01062 Dresden, Germany.
[Ludwig, Barbara] Tech Univ Dresden, Univ Clin Carl Gustav Carus, Helmholtz Ctr Munich, Paul Langerhans Inst Dresden, Dresden, Germany.
[Ludwig, Barbara] DZD German Ctr Diabet Res, Dresden, Germany.
[Choudhary, Pratik] Kings Coll London, Weston Educ Ctr, Diabet Res Grp, London WC2R 2LS, England.
[Khovatchev, Boris] Univ Virginia, Ctr Diabet Technol, Charlottesville, VA USA.
[Rickels, Michael R.] Univ Penn, Dept Med, Perelman Sch Med, Div Endocrinol Diabet & Metab, Philadelphia, PA 19104 USA.
[Sykes, Megan] Columbia Univ, Med Ctr, Columbia Ctr Translat Immunol, New York, NY USA.
[Hwa, Albert] Juvenile Diabet Res Fdn, New York, NY USA.
[Stanley, Edward] Murdoch Childrens Res Inst, Melbourne, Vic, Australia.
[Stanley, Edward] Monash Univ, Melbourne, Vic 3004, Australia.
[Ricordi, Camillo] Univ Miami, Diabet Res Inst, Coral Gables, FL 33124 USA.
[Zimmerman, Mark] BetaLogics, Raritan, NJ USA.
[Greenstein, Julia] Juvenile Diabet Res Fdn, Discovery Res, New York, NY USA.
[Montanya, Eduard] Univ Barcelona, Hosp Univ Bellvitge, CIBERDEM, Bellvitge Biomed Res Inst IDIBELL, Barcelona, Spain.
[Otonkoski, Timo] Univ Helsinki, Childrens Hosp, Helsinki, Finland.
[Otonkoski, Timo] Univ Helsinki, Biomedicum Stem Cell Ctr, Helsinki, Finland.
RP Markmann, JF (reprint author), Massachusetts Gen Hosp, 55 Fruit St,WHT 517, Boston, MA 02114 USA.
EM jmarkmann@partners.org
RI Stabler, Cherie/E-8227-2011
NR 32
TC 3
Z9 3
U1 1
U2 6
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0041-1337
EI 1534-6080
J9 TRANSPLANTATION
JI Transplantation
PD JUL
PY 2016
VL 100
IS 7
BP E25
EP E31
DI 10.1097/TP.0000000000001054
PG 7
WC Immunology; Surgery; Transplantation
SC Immunology; Surgery; Transplantation
GA DP0AG
UT WOS:000378149300001
PM 27082827
ER
PT J
AU Ferreira, M
Firmino, MJ
Marques, EA
Santos, PC
Duarte, JA
AF Ferreira, Margarida
Firmino, Machado J.
Marques, Elisa A.
Santos, Paula C.
Duarte, Jose A.
TI Are corticosteroids useful in all degrees of severity and rapid recovery
of Bell's palsy?
SO ACTA OTO-LARYNGOLOGICA
LA English
DT Article
DE Facial palsy; medical therapy; muscular training; Sunnybrook Facial
Grading System; House-Brackmann Facial Grading System
ID NEUROMUSCULAR REEDUCATION; GRADING SYSTEM; REHABILITATION; TRIAL
AB Conclusions The results provide preliminary evidence that corticosteroids were not effective in all grades of dysfunction and for achieving a rapid remission in the early phase of BP, highlighting the need to define standard and rigorous criteria to prescribe corticosteroids in these patients. Objectives The main aim of this study was to investigate whether the use of corticosteroids better associated than paralleled with neuromuscular training (C+FNT) is more effective than facial neuromuscular training (FNT) applied alone, in terms of recovery degree and facial symmetry during the early phase of Bell's palsy (BP). Patients and methods A prospective single-blinded study involved 73 patients: the C+FNT group (n=42; median age = 37.5 years) and FNT group (n=31; median age = 49.0 years). Patients were assessed before and 6 weeks after treatment by House-Brackmann (HB-FGS) and Sunnybrook Facial Grading System (SB-FGS). Results Recovery degree and facial symmetry improved significantly in both groups (p<0.001), without differences between groups (p>0.05). However, the C+FNT group displayed better outcomes for cheek (p=0.004) and mouth (p=0.022) resting symmetry at SB-FGS, instead of compared to the FNT group. The corticosteroids had no significant effect on all recovery degrees (p=0.992) and rapid remission (p=0.952). Multiple linear regression analysis showed that the type of intervention was not a significant predictor for recovery degree (p=0.917).
C1 [Ferreira, Margarida; Santos, Paula C.; Duarte, Jose A.] Univ Porto, Fac Sport, Res Ctr Phys Act Hlth & Leisure, P-914200 Oporto, Portugal.
[Ferreira, Margarida] CESPU, North Polytech Inst Hlth, Dept Physiotherapy Paredes & Vila Nova De Famalic, Gandra, Portugal.
[Firmino, Machado J.] Dept Publ Hlth Occidental, Oporto, Portugal.
[Marques, Elisa A.] Univ Inst Maia ISMAI, Res Ctr Sports Sci Hlth & Human Dev CIDESD, Maia, Portugal.
[Marques, Elisa A.] NIA, NIH, Bethesda, MD 20892 USA.
[Santos, Paula C.] Polytech Inst Porto, Sch Hlth Technol, Dept Phys Therapy, Vila Nova De Gaia, Portugal.
RP Ferreira, M (reprint author), Univ Porto, Fac Sport, Res Ctr Phys Act Hlth & Leisure, P-914200 Oporto, Portugal.
EM margasufer@gmail.com
NR 20
TC 0
Z9 0
U1 1
U2 2
PU TAYLOR & FRANCIS LTD
PI ABINGDON
PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND
SN 0001-6489
EI 1651-2251
J9 ACTA OTO-LARYNGOL
JI Acta Oto-Laryngol.
PD JUL
PY 2016
VL 136
IS 7
BP 736
EP 741
DI 10.3109/00016489.2016.1154604
PG 6
WC Otorhinolaryngology
SC Otorhinolaryngology
GA DO6ZQ
UT WOS:000377932400017
PM 27003272
ER
PT J
AU Zhang, YS
McNerny, EG
Terajima, M
Raghavan, M
Romanowicz, G
Zhang, ZP
Zhang, HH
Kamiya, N
Tantillo, M
Zhu, PZ
Scott, GJ
Ray, MK
Lynch, M
Ma, PX
Morris, MD
Yamauchi, M
Kohn, DH
Mishina, Y
AF Zhang, Yanshuai
McNerny, Erin Gatenby
Terajima, Masahiko
Raghavan, Mekhala
Romanowicz, Genevieve
Zhang, Zhanpeng
Zhang, Honghao
Kamiya, Nobuhiro
Tantillo, Margaret
Zhu, Peizhi
Scott, Gregory J.
Ray, Manas K.
Lynch, Michelle
Ma, Peter X.
Morris, Michael D.
Yamauchi, Mitsuo
Kohn, David H.
Mishina, Yuji
TI Loss of BMP signaling through BMPR1A in osteoblasts leads to greater
collagen cross-link maturation and material-level mechanical properties
in mouse femoral trabecular compartments
SO BONE
LA English
DT Article
DE BMP receptor type 1A; Collagen cross-links; Cortical geometry; Bone
quality; Biomechanical properties
ID INCREASES BONE MASS; IA RECEPTOR BMPRIA; MINERAL-TO-MATRIX; CORTICAL
BONE; FRAGILITY; MICE; FRACTURE; STRENGTH; TISSUE; NANOINDENTATION
AB Bone morphogenetic protein (BMP) signaling pathways play critical roles in skeletal development and new bone formation. Our previous study, however, showed a negative impact of BMP signaling on bone mass because of the osteoblast-specific loss of a BMP receptor (i.e. BMPR1A) showing increased trabecular bone volume and mineral density in mice. Here, we investigated the bone quality and biomechanical properties of the higher bone mass associated with BMPR1A deficiency using the osteoblast-specific Bmpr 1a conditional knockout (cKO) mouse model. Collagen biochemical analysis revealed greater levels of the mature cross-link pyridinoline in the cKO bones, in parallel with upregulation of collagen modifying enzymes. Raman spectroscopy distinguished increases in the mature to immature cross-link ratio and mineral to matrix ratio in the trabecular compartments of cKO femora, but not in the cortical compartments. The mineral crystallinity was unchanged in the cKO in either the trabecular or cortical compartments. Further, we tested the intrinsic material properties by nanoindentation and found significantly higher hardness and elastic modulus in the cKO trabecular compartments, but not in the cortical compartments. Four point bending tests of cortical compartments showed lower structural biomechanical properties (i.e. strength and stiffness) in the cKO bones due to the smaller cortical areas. However, there were no significant differences in biomechanical performance at the material level, which was consistent with the nanoindentation test results on the cortical compartment These studies emphasize the pivotal role of BMPR1A in the determination of bone quality and mechanical integrity under physiological conditions, with different impact on femoral cortical and trabecular compartments. (C) 2016 Elsevier Inc. All rights reserved.
C1 [Zhang, Yanshuai; Romanowicz, Genevieve; Zhang, Zhanpeng; Zhang, Honghao; Kamiya, Nobuhiro; Tantillo, Margaret; Ma, Peter X.; Kohn, David H.; Mishina, Yuji] Univ Michigan, Sch Dent, Dept Biol & Mat Sci, 1011 N Univ Ave, Ann Arbor, MI 48109 USA.
[McNerny, Erin Gatenby; Kohn, David H.] Univ Michigan, Coll Engn, Biomed Engn, Ann Arbor, MI 48109 USA.
[Raghavan, Mekhala; Zhu, Peizhi; Morris, Michael D.] Univ Michigan, Coll Literature Sci & Arts, Dept Chem, Ann Arbor, MI 48109 USA.
[Terajima, Masahiko; Yamauchi, Mitsuo] Univ N Carolina, Sch Dent, Chapel Hill, NC USA.
[Kamiya, Nobuhiro; Mishina, Yuji] NIEHS, Reprod & Dev Biol Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.
[Scott, Gregory J.; Ray, Manas K.; Mishina, Yuji] NIEHS, Knock Out Core, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.
[Kamiya, Nobuhiro] Texas Scottish Rite Hosp Children, Ctr Excellence Hip Disorders, Dallas, TX 75219 USA.
[Kamiya, Nobuhiro] Tenri Univ, Fac Budo & Sport Studies, Nara, Japan.
[Lynch, Michelle] Univ Michigan, Sch Dent, Res Off, Ann Arbor, MI 48109 USA.
RP Mishina, Y (reprint author), Univ Michigan, Sch Dent, Dept Biol & Mat Sci, 1011 N Univ Ave, Ann Arbor, MI 48109 USA.
EM mishina@umich.edu
FU National Institutes of Health [R01DE020843, E5071003-11, R01ARAR047969];
Department of Defense [DOD W81XWH-12-2-0008]; NIH/NCRR [S10RR026475-01]
FX We thank Drs. Hank Kronenberg and Tatsuya Kobayashi for providing
Col1CreERTM mice; Dr. Gurjit Mandair for advice on Raman analyses, Drs.
Kenneth Kozloff and Joseph Perosky for advice on nano indentation; Ms.
Toni Ward, Ms. Kelly McCann and Ms. Xixi Wang for maintaining mouse
colonies; Ms. Caitlyn Molloy for excellent technical assistance; and Dr.
Judith Connett for critical reading and editing of this manuscript. This
study is supported by the National Institutes of Health (R01DE020843 and
E5071003-11 to YM, R01ARAR047969 to MDM) and Department of Defense (DOD
W81XWH-12-2-0008 to MXP). The mu CT core at the School of Dentistry,
University of Michigan is funded in part by NIH/NCRR S10RR026475-01.
NR 61
TC 1
Z9 1
U1 3
U2 8
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 8756-3282
EI 1873-2763
J9 BONE
JI Bone
PD JUL
PY 2016
VL 88
BP 74
EP 84
DI 10.1016/j.bone.2016.04.022
PG 11
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA DO6WV
UT WOS:000377925100010
PM 27113526
ER
PT J
AU Chu, CH
Wang, SJ
Li, CL
Chen, SH
Hu, CF
Chung, YL
Chen, SL
Wang, QS
Lu, RB
Gao, HM
Hong, JS
AF Chu, Chun-Hsien
Wang, Shijun
Li, Chia-Ling
Chen, Shih-Heng
Hu, Chih-Fen
Chung, Yi-Lun
Chen, Shiou-Lan
Wang, Qingshan
Lu, Ru-Band
Gao, Hui-Ming
Hong, Jau-Shyong
TI Neurons and astroglia govern microglial endotoxin tolerance through
macrophage colony-stimulating factor receptor-mediated ERK1/2 signals
SO BRAIN BEHAVIOR AND IMMUNITY
LA English
DT Article
DE Microglia; Endotoxin tolerance; Neurons; Astroglia; M-CSF; CSF1R;
ERK1/2; M2-like microglia; Neuroprotection
ID LANGERHANS CELLS; IN-VITRO; PROGENITOR-CELL; GENE-EXPRESSION;
NERVOUS-SYSTEM; LIPOPOLYSACCHARIDE; BRAIN; CSF-1; BETA;
NEURODEGENERATION
AB Endotoxin tolerance (ET) is a reduced responsiveness of innate immune cells like macrophages/monocytes to an endotoxin challenge following a previous encounter with the endotoxin. Although ET in peripheral systems has been well studied, little is known about ET in the brain. The present study showed that brain immune cells, microglia, being different from peripheral macrophages, displayed non-cell autonomous mechanisms in ET formation. Specifically, neurons and astroglia were indispensable for microglial ET. Macrophage colony-stimulating factor (M-CSF) secreted from these non-immune cells was essential for governing microglial ET. Neutralization of M-CSF deprived the neuron-glia conditioned medium of its ability to enable microglia to form ET when microglia encountered two lipopolysaccharide (LPS) treatments. Recombinant M-CSF protein rendered enriched microglia refractory to the second LPS challenge leading to microglial ET. Activation of microglial M-CSF receptor (M-CSFR; also known as CSF1R) and the downstream ERK1/2 signals was responsible for M-CSF-mediated microglial ET. Endotoxin-tolerant microglia in neuron-glia cultures displayed M2-like polarized phenotypes, as shown by upregulation of M2 marker Arg-1, elevated production of anti-inflammatory cytokine interleukin 10, and decreased secretion of pro-inflammatory mediators (tumor necrosis factor a, nitric oxide, prostaglandin E2 and interleukin 1(3). Endotoxin-tolerant microglia protected neurons against LPS-elicited inflammatory insults, as shown by reduced neuronal damages in LPS pre-treatment group compared with the group without LPS pre-treatment. Moreover, while neurons and astroglia became injured during chronic neuroinflammation, microglia failed to form ET. Thus, this study identified a distinct non-cell autonomous mechanism of microglial ET. Interactions of M-CSF secreted by neurons and astroglia with microglial M-CSFR programed microglial ET. Loss of microglial ET could be an important pathogenetic mechanism of inflammation-associated neuronal damages. (C) 2016 Elsevier Inc. All rights reserved.
C1 [Chu, Chun-Hsien; Wang, Shijun; Chen, Shih-Heng; Hu, Chih-Fen; Wang, Qingshan; Hong, Jau-Shyong] NIEHS, Neurobiol Lab, Div Intramural Res, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.
[Chu, Chun-Hsien] Natl Cheng Kung Univ, Natl Cheng Kung Univ Hosp, Inst Mol Med, Coll Med, Tainan 70101, Taiwan.
[Li, Chia-Ling; Lu, Ru-Band] Natl Cheng Kung Univ, Natl Cheng Kung Univ Hosp, Dept Psychiat, Coll Med, Tainan 70101, Taiwan.
[Hu, Chih-Fen] Triserv Gen Hosp, Grad Inst Med Sci, Dept Pediat, Natl Def Med Ctr, Taipei 11401, Taiwan.
[Chung, Yi-Lun] Natl Cheng Kung Univ, Inst Basic Med Sci, Tainan 70101, Taiwan.
[Chen, Shiou-Lan] Kaohsiung Med Univ, Sch Med, Dept Neurol, Kaohsiung 80780, Taiwan.
[Lu, Ru-Band] Natl Cheng Kung Univ, Inst Behav Med, Tainan 70101, Taiwan.
[Lu, Ru-Band] Natl Cheng Kung Univ, Inst Allied Hlth Sci, Tainan 70101, Taiwan.
[Lu, Ru-Band] Natl Cheng Kung Univ, Addict Res Ctr, Tainan 70101, Taiwan.
[Gao, Hui-Ming] Nanjing Univ, Model Anim Res Ctr, 12 Xuefu Rd, Nanjing 210061, Jiangsu, Peoples R China.
[Gao, Hui-Ming] Nanjing Univ, MOE Key Lab Model Anim Dis Study, 12 Xuefu Rd, Nanjing 210061, Jiangsu, Peoples R China.
[Gao, Hui-Ming] Nanjing Univ, Nanjing Biomed Res Inst, Nanjing 210061, Jiangsu, Peoples R China.
RP Gao, HM (reprint author), Nanjing Univ, Model Anim Res Ctr, 12 Xuefu Rd, Nanjing 210061, Jiangsu, Peoples R China.; Gao, HM (reprint author), Nanjing Univ, MOE Key Lab Model Anim Dis Study, 12 Xuefu Rd, Nanjing 210061, Jiangsu, Peoples R China.
EM gaohm@nju.edu.cn
FU Intramural Research Program of the NIH/NIEHS in the United States
[ES090082]; National Natural Science Foundation of China [31471006,
21577004]; national high technology research and development program of
China (863 program) [2014 AA021601]; award to high-level innovative and
entrepreneurial talents of Jiangsu Province of China
FX This work was supported by the Intramural Research Program of the
NIH/NIEHS in the United States (ES090082) to J.-S.H., the National
Natural Science Foundation of China (Nos. 31471006 and 21577004), the
national high technology research and development program of China (863
program; No. 2014 AA021601), and the award to high-level innovative and
entrepreneurial talents of Jiangsu Province of China to H.-M.G. We thank
Anthony Lockhart for the assistance with animal colony management and
maintenance of the timed pregnant mice.
NR 56
TC 2
Z9 2
U1 3
U2 7
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0889-1591
EI 1090-2139
J9 BRAIN BEHAV IMMUN
JI Brain Behav. Immun.
PD JUL
PY 2016
VL 55
SI SI
BP 260
EP 272
DI 10.1016/j.bbi.2016.04.015
PG 13
WC Immunology; Neurosciences
SC Immunology; Neurosciences & Neurology
GA DO8FT
UT WOS:000378019100024
PM 27132056
ER
PT J
AU Chen, Q
Shou, P
Zheng, C
Jiang, M
Cao, G
Yang, Q
Cao, J
Xie, N
Velletri, T
Zhang, X
Xu, C
Zhang, L
Yang, H
Hou, J
Wang, Y
Shi, Y
AF Chen, Q.
Shou, P.
Zheng, C.
Jiang, M.
Cao, G.
Yang, Q.
Cao, J.
Xie, N.
Velletri, T.
Zhang, X.
Xu, C.
Zhang, L.
Yang, H.
Hou, J.
Wang, Y.
Shi, Y.
TI Fate decision of mesenchymal stem cells: adipocytes or osteoblasts?
SO CELL DEATH AND DIFFERENTIATION
LA English
DT Review
ID FIBROBLAST-GROWTH-FACTOR; HUMAN ADIPOSE-TISSUE; THERAPY POSITION
STATEMENT; MARROW STROMAL CELLS; OSTEOGENIC DIFFERENTIATION;
BONE-MARROW; ADIPOGENIC DIFFERENTIATION; PROGENITOR CELLS; TGF-BETA;
IN-VITRO
AB Mesenchymal stem cells (MSCs), a non-hematopoietic stem cell population first discovered in bone marrow, are multipotent cells capable of differentiating into mature cells of several mesenchymal tissues, such as fat and bone. As common progenitor cells of adipocytes and osteoblasts, MSCs are delicately balanced for their differentiation commitment. Numerous in vitro investigations have demonstrated that fat-induction factors inhibit osteogenesis, and, conversely, bone-induction factors hinder adipogenesis. In fact, a variety of external cues contribute to the delicate balance of adipo-osteogenic differentiation of MSCs, including chemical, physical, and biological factors. These factors trigger different signaling pathways and activate various transcription factors that guide MSCs to commit to either lineage. The dysregulation of the adipo-osteogenic balance has been linked to several pathophysiologic processes, such as aging, obesity, osteopenia, osteopetrosis, and osteoporosis. Thus, the regulation of MSC differentiation has increasingly attracted great attention in recent years. Here, we review external factors and their signaling processes dictating the reciprocal regulation between adipocytes and osteoblasts during MSC differentiation and the ultimate control of the adipo-osteogenic balance.
C1 [Chen, Q.; Zhang, L.; Yang, H.; Hou, J.; Shi, Y.] Soochow Univ, Inst Translat Med, Affiliated Hosp 1, Suzhou 215006, Peoples R China.
[Chen, Q.; Shou, P.; Zheng, C.; Jiang, M.; Cao, G.; Yang, Q.; Cao, J.; Xie, N.; Velletri, T.; Zhang, X.; Xu, C.; Wang, Y.; Shi, Y.] Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Hlth Sci, Key Lab Stem Cell Biol, Shanghai 200031, Peoples R China.
[Zhang, L.; Shi, Y.] Rutgers Robert Wood Johnson Med Sch, Child Hlth Inst New Jersey, New Brunswick, NJ 08901 USA.
[Chen, Q.] NIEHS, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.
RP Shi, Y (reprint author), Soochow Univ, Inst Translat Med, Affiliated Hosp 1, Suzhou 215006, Peoples R China.; Wang, Y (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Hlth Sci, Shanghai 200025, Peoples R China.
EM yingwang@sibs.ac.cn; yfshi@suda.edu.cn
OI Shou, Peishun/0000-0001-7685-7471
FU Scientific Innovation Project of the Chinese Academy of Sciences
[XDA01040107]; Ministry of Science and Technology of China
[2015CB964500]; National Natural Science Foundation of China [81330046,
81530043, 81273316, 81571612]; Shanghai Rising-Star Program
[14QA1404200]
FX We are indebted to those whose work is not discussed due to space
limitations. This work is supported by grants from Scientific Innovation
Project of the Chinese Academy of Sciences (XDA01040107), the Ministry
of Science and Technology of China (2015CB964500), National Natural
Science Foundation of China (81330046, 81530043, 81273316, 81571612),
and Shanghai Rising-Star Program (14QA1404200).
NR 154
TC 21
Z9 21
U1 19
U2 38
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1350-9047
EI 1476-5403
J9 CELL DEATH DIFFER
JI Cell Death Differ.
PD JUL
PY 2016
VL 23
IS 7
BP 1128
EP 1139
DI 10.1038/cdd.2015.168
PG 12
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA DO6YN
UT WOS:000377929500005
PM 26868907
ER
PT J
AU Balkus, JE
Brown, ER
Hillier, SL
Coletti, A
Ramjee, G
Mgodi, N
Makanani, B
Reid, C
Martinson, F
Soto-Torres, L
Karim, SSA
Chirenje, ZM
AF Balkus, Jennifer E.
Brown, Elizabeth R.
Hillier, Sharon L.
Coletti, Anne
Ramjee, Gita
Mgodi, Nyaradzo
Makanani, Bonus
Reid, Cheri
Martinson, Francis
Soto-Torres, Lydia
Karim, Salim S. Abdool
Chirenje, Zvavahera M.
TI oral and injectable contraceptive use and HIV acquisition risk among
women in four African countries: a secondary analysis of data from a
microbicide trial (vol 93, pg 25, 2016)
SO CONTRACEPTION
LA English
DT Correction
C1 [Balkus, Jennifer E.; Brown, Elizabeth R.] Fred Hutchinson Canc Res Ctr, Vaccine & Infect Dis Div, 1124 Columbia St, Seattle, WA 98104 USA.
[Hillier, Sharon L.] Univ Pittsburgh, Sch Med, Dept Obstet Gynecol & Reprod Sci, Pittsburgh, PA USA.
[Hillier, Sharon L.] Univ Pittsburgh, Magee Womens Res Inst, Sch Med, Pittsburgh, PA USA.
[Coletti, Anne] FHI360, Durham, NC USA.
[Ramjee, Gita] South Africa Med Res Council, HIV Prevent Res Unit, Durban, South Africa.
[Mgodi, Nyaradzo; Chirenje, Zvavahera M.] Univ Zimbabwe Univ Calif San Francisco Res Progra, Harare, Zimbabwe.
[Makanani, Bonus] Univ Malawi, Coll Med, Blantyre, Malawi.
[Reid, Cheri] Ctr Infect Dis Res Zambia, Lusaka, Zambia.
[Martinson, Francis] Univ North Carolina Project, Kamuzu Cent Hosp, Lilongwe, Malawi.
[Soto-Torres, Lydia] NIH, Bldg 10, Bethesda, MD 20892 USA.
[Karim, Salim S. Abdool] Univ KwaZulu Natal, Nelson R Mandela Sch Med, Doris Duke Med Res Inst, Ctr AIDS Program Res South Africa, Congella, South Africa.
[Karim, Salim S. Abdool] Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY USA.
RP Balkus, JE (reprint author), Fred Hutchinson Canc Res Ctr, Vaccine & Infect Dis Div, 1124 Columbia St, Seattle, WA 98104 USA.
EM jbalkus@fhcrc.org
NR 1
TC 0
Z9 0
U1 2
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0010-7824
EI 1879-0518
J9 CONTRACEPTION
JI Contraception
PD JUL
PY 2016
VL 94
IS 1
BP 95
EP 95
DI 10.1016/j.contraception.2016.03.018
PG 1
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA DO2TG
UT WOS:000377632400018
ER
PT J
AU Graham, AL
Nussey, DH
Lloyd-Smith, JO
Longbottom, D
Maley, M
Pemberton, JM
Pilkington, JG
Prager, KC
Smith, L
Watt, KA
Wilson, K
McNeilly, TN
Brulisauer, F
AF Graham, A. L.
Nussey, D. H.
Lloyd-Smith, J. O.
Longbottom, D.
Maley, M.
Pemberton, J. M.
Pilkington, J. G.
Prager, K. C.
Smith, L.
Watt, K. A.
Wilson, K.
McNeilly, T. N.
Brulisauer, F.
TI Exposure to viral and bacterial pathogens among Soay sheep (Ovis aries)
of the St Kilda archipelago
SO EPIDEMIOLOGY AND INFECTION
LA English
DT Article
DE Epidemiology; parasites
ID INTERROGANS SEROVAR HARDJO; LINKED-IMMUNOSORBENT-ASSAY; ENZOOTIC
ABORTION; MAINTENANCE HOST; POPULATION; ANTIBODIES; DISEASE; DIAGNOSIS;
VIRUSES; ISLAND
AB We assessed evidence of exposure to viruses and bacteria in an unmanaged and long-isolated population of Soay sheep (Ovis aries) inhabiting Hirta, in the St Kilda archipelago, 65 km west of Benbecula in the Outer Hebrides of Scotland. The sheep harbour many metazoan and protozoan parasites but their exposure to viral and bacterial pathogens is unknown. We tested for herpes viral DNA in leucocytes and found that 21 of 42 tested sheep were infected with ovine herpesvirus 2 (OHV-2). We also tested 750 plasma samples collected between 1997 and 2010 for evidence of exposure to seven other viral and bacterial agents common in domestic Scottish sheep. We found evidence of exposure to Leptospira spp., with overall seroprevalence of 6.5%. However, serological evidence indicated that the population had not been exposed to border disease, parainfluenza, maedi-visna, or orf viruses, nor to Chlamydia abortus. Some sheep tested positive for antibodies against Mycobacterium avium subsp. paratuberculosis (MAP) but, in the absence of retrospective faecal samples, the presence of this infection could not be confirmed. The roles of importation, the pathogen-host interaction, nematode co-infection and local transmission warrant future investigation, to elucidate the transmission ecology and fitness effects of the few viral and bacterial pathogens on Hirta.
C1 [Graham, A. L.] Princeton Univ, Dept Ecol & Evolutionary Biol, 106a Guyot Hall, Princeton, NJ 08544 USA.
[Graham, A. L.; Lloyd-Smith, J. O.; Prager, K. C.] NIH, Fogarty Int Ctr, Bldg 10, Bethesda, MD 20892 USA.
[Nussey, D. H.; Pemberton, J. M.; Pilkington, J. G.; Watt, K. A.] Univ Edinburgh, Sch Biol Sci, Inst Evolutionary Biol, Edinburgh, Midlothian, Scotland.
[Lloyd-Smith, J. O.; Prager, K. C.] Univ Calif Los Angeles, Dept Ecol & Evolutionary Biol, Los Angeles, CA USA.
[Longbottom, D.; Maley, M.; McNeilly, T. N.] Moredun Res Inst, Pentlands Sci Pk, Penicuik, Midlothian, Scotland.
[Smith, L.] Anim & Plant Hlth Agcy, Addlestone, Surrey, England.
[Wilson, K.] Univ Lancaster, Lancaster Environm Ctr, Lancaster, England.
[Brulisauer, F.] Scotlands Rural Coll, SAC Consulting Vet Serv, Inverness, Scotland.
RP Graham, AL (reprint author), Princeton Univ, Dept Ecol & Evolutionary Biol, 106a Guyot Hall, Princeton, NJ 08544 USA.; Brulisauer, F (reprint author), Scotlands Rural Coll, SAC Consulting Vet Serv, Inverness, Scotland.
EM algraham@princeton.edu; Franz.Brulisauer@sruc.ac.uk
RI APHA, Staff publications/E-6082-2010; Pemberton, Josephine/F-3100-2010;
Graham, Andrea/A-8808-2010; Nussey, Daniel/F-4155-2010; Lloyd-Smith,
James/K-4080-2012
OI Graham, Andrea/0000-0002-6580-2755; Lloyd-Smith,
James/0000-0001-7941-502X
FU U.K. Natural Environment and Biotechnology & Biological Sciences
Research Councils (including BBSRC Fellowships); Wellcome Trust;
Research and Policy for Infectious Disease Dynamics (RAPIDD) program of
the Science and Technology Directorate, U.S. Department of Homeland
Security; Fogarty International Center of the National Institutes of
Health
FX This work was supported by the U.K. Natural Environment and
Biotechnology & Biological Sciences Research Councils (including BBSRC
Fellowships to A.L.G. and D.H.N.), the Wellcome Trust, and the Research
and Policy for Infectious Disease Dynamics (RAPIDD) program of the
Science and Technology Directorate, U.S. Department of Homeland
Security, and the Fogarty International Center of the National
Institutes of Health.
NR 40
TC 0
Z9 0
U1 3
U2 10
PU CAMBRIDGE UNIV PRESS
PI NEW YORK
PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA
SN 0950-2688
EI 1469-4409
J9 EPIDEMIOL INFECT
JI Epidemiol. Infect.
PD JUL
PY 2016
VL 144
IS 9
BP 1879
EP 1888
DI 10.1017/S0950268816000017
PG 10
WC Public, Environmental & Occupational Health; Infectious Diseases
SC Public, Environmental & Occupational Health; Infectious Diseases
GA DO5JV
UT WOS:000377820300010
PM 26829883
ER
PT J
AU Kwon, J
Wang, AB
Burke, DJ
Boudreau, HE
Lekstrom, KJ
Korzeniowska, A
Sugamata, R
Kim, YS
Yi, L
Ersoy, I
Jaeger, S
Palaniappan, K
Ambruso, DR
Jackson, SH
Leto, TL
AF Kwon, Jaeyul
Wang, Aibing
Burke, Devin J.
Boudreau, Howard E.
Lekstrom, Kristen J.
Korzeniowska, Agnieszka
Sugamata, Ryuichi
Kim, Yong-Soo
Yi, Liang
Ersoy, Ilker
Jaeger, Stefan
Palaniappan, Kannappan
Ambruso, Daniel R.
Jackson, Sharon H.
Leto, Thomas L.
TI Peroxiredoxin 6 (Prdx6) supports NADPH oxidase1 (Nox1)-based superoxide
generation and cell migration
SO FREE RADICAL BIOLOGY AND MEDICINE
LA English
DT Article
DE Nox1; NADPH oxidase; Peroxiredoxin 6; Prdx 6; Phospholipase A(2);
Peroxidase; Cell migration
ID PHOSPHOLIPASE A(2) ACTIVITY; COLON EPITHELIAL-CELLS; OXYGEN SPECIES
GENERATION; FORMYL PEPTIDE RECEPTOR; INNATE IMMUNE-RESPONSE;
SMOOTH-MUSCLE-CELLS; GLUTATHIONE-PEROXIDASE; NAD(P)H OXIDASE-1;
ARACHIDONIC-ACID; KINASE-C
AB Nox1 is an abundant source of reactive oxygen species (ROS) in colon epithelium recently shown to function in wound healing and epithelial homeostasis. We identified Peroxiredoxin 6 (Prdx6) as a novel binding partner of Nox activator 1 (Noxa1) in yeast two-hybrid screening experiments using the Noxa1 SH3 domain as bait. Prdx6 is a unique member of the Prdx antioxidant enzyme family exhibiting both glutathione peroxidase and phospholipase A(2) activities. We confirmed this interaction in cells over expressing both proteins, showing Prdx6 binds to and stabilizes wild type Noxal, but not the SH3 domain mutant form, Noxa1 W436R. We demonstrated in several cell models that Prdx6 knockdown suppresses Nox1 activity, whereas enhanced Prdx6 expression supports higher Nox1-derived superoxide production. Both peroxidase- and lipase-deficient mutant forms of Prdx6 (Prdx6 C47S and S32A, respectively) failed to bind to or stabilize Nox1 components or support Nox1-mediated superoxide generation. Furthermore, the transition-state substrate analogue inhibitor of Prdx6 phospholipase A(2) activity (MJ-33) was shown to suppress Nox1 activity, suggesting Nox1 activity is regulated by the phospholipase activity of Prdx6. Finally, wild type Prdx6, but not lipase or peroxidase mutant forms, supports Nox1-mediated cell migration in the HCT-116 colon epithelial cell model of wound closure. These findings highlight a novel pathway in which this antioxidant enzyme positively regulates an oxidant-generating system to support cell migration and wound healing. Published by Elsevier Inc.
C1 [Kwon, Jaeyul; Burke, Devin J.; Boudreau, Howard E.; Lekstrom, Kristen J.; Korzeniowska, Agnieszka; Sugamata, Ryuichi; Leto, Thomas L.] NIAID, Host Def Lab, NIH, Rockville, MD USA.
[Kwon, Jaeyul] Chungnam Natl Univ, Sch Med, Dept Med Educ, Daejeon 301747, South Korea.
[Wang, Aibing; Yi, Liang; Jackson, Sharon H.] Natl Inst Minor Hlth & Hlth Disparities, Diabet Cluster, NIH, Bethesda, MD USA.
[Kim, Yong-Soo] NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA.
[Ersoy, Ilker] Univ Missouri, Sch Med, Dept Pathol & Anant Sci, Columbia, MO USA.
[Jaeger, Stefan] NIH, Lister Hill Natl Ctr Biomed Commun, Natl Lib Med, Bldg 10, Bethesda, MD 20892 USA.
[Palaniappan, Kannappan] Univ Missouri, Dept Comp Sci, Columbia, MO USA.
[Ambruso, Daniel R.] Univ Colorado, Sch Med, Dept Pediat, Denver, CO 80202 USA.
RP Leto, TL (reprint author), NIAID, Host Def Lab, NIH, Rockville, MD USA.
EM tleto@nih.gov
RI Ersoy, Ilker/N-2116-2016
OI Ersoy, Ilker/0000-0003-2650-4496
FU Intramural Research Program of NIH, USA; National Institute of Allergy
and Infectious Diseases [ZO1-AI-000614]; Chungnam National University,
South Korea
FX This work was supported by funds from the Intramural Research Program of
the NIH, USA, National Institute of Allergy and Infectious Diseases
(ZO1-AI-000614) and, in part, by research funds from Chungnam National
University, South Korea. The authors are grateful to Dr. Miklos Geiszt
(Semmelweis University) for providing antibodies against Noxal and Dr.
Gary M. Bokoch (deceased, Scripps Research Institute) for providing the
Myc-tagged Noxal cDNA.
NR 67
TC 2
Z9 2
U1 2
U2 8
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0891-5849
EI 1873-4596
J9 FREE RADICAL BIO MED
JI Free Radic. Biol. Med.
PD JUL
PY 2016
VL 96
BP 99
EP 115
DI 10.1016/j.freeradbiomed.2016.04.009
PG 17
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA DO2OO
UT WOS:000377619600010
PM 27094494
ER
PT J
AU Mattson, MP
AF Mattson, Mark P.
TI Intermittent bioenergetic and oxidative challenges promote optimal brain
function
SO FREE RADICAL BIOLOGY AND MEDICINE
LA English
DT Meeting Abstract
CT Conference of the Society-for-Free-Radical-Research-Europe (SFRR-E)
CY JUN 08-11, 2016
CL Budapest, HUNGARY
SP Soc Free Rad Res Europe
C1 [Mattson, Mark P.] NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA.
NR 0
TC 0
Z9 0
U1 4
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0891-5849
EI 1873-4596
J9 FREE RADICAL BIO MED
JI Free Radic. Biol. Med.
PD JUL
PY 2016
VL 96
SU 1
MA A-03
BP S1
EP S2
DI 10.1016/j.freeradbiomed.2016.04.164
PG 2
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA DO2NY
UT WOS:000377617900004
ER
PT J
AU Tran, AH
Best, BM
Stek, A
Wang, JJ
Capparelli, EV
Burchett, SK
Kreitchmann, R
Rungruengthanakit, K
George, K
Cressey, TR
Chakhtoura, N
Smith, E
Shapiro, DE
Mirochnick, M
AF Tran, Anna H.
Best, Brookie M.
Stek, Alice
Wang, Jiajia
Capparelli, Edmund V.
Burchett, Sandra K.
Kreitchmann, Regis
Rungruengthanakit, Kittipong
George, Kathleen
Cressey, Tim R.
Chakhtoura, Nahida
Smith, Elizabeth
Shapiro, David E.
Mirochnick, Mark
CA IMPAACT P1026s Protocol Team
TI Pharmacokinetics of Rilpivirine in HIV-Infected Pregnant Women
SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
LA English
DT Article
DE rilpivirine; pregnancy; HIV; pharmacokinetics
ID STEADY-STATE PHARMACOKINETICS; DRUG-METABOLISM; EFAVIRENZ; EXPOSURE;
PHARMACOGENETICS; ANTIRETROVIRALS; POSTPARTUM; INHIBITOR; SAFETY; TWICE
AB Background: Rilpivirine pharmacokinetics is defined by its absorption, distribution, metabolism, and excretion. Pregnancy can affect these factors by changes in cardiac output, protein binding, volume of distribution, and cytochrome P450 (CYP) 3A4 activity. Rilpivirine is metabolized by CYP3A4. The impact of pregnancy on rilpivirine pharmacokinetics is largely unknown.
Methods: International Maternal Pediatric Adolescent AIDS Clinical Trials P1026s is a multicenter, nonblinded, prospective study evaluating antiretroviral pharmacokinetics in HIV-infected pregnant women that included a cohort receiving rilpivirine 25 mg once daily as part of their combination antiretrovirals for clinical care. Thirty-two women were enrolled in this study. Intensive pharmacokinetic sampling was performed at steady state during the second trimester, the third trimester, and postpartum. Maternal and umbilical cord blood samples were obtained at delivery. Plasma rilpivirine concentration was measured using liquid chromatography-mass spectrometry; lower limit of quantitation was 10 ng/mL.
Results: Median (range) AUC(0-24) were 1969 (867-4987, n = 15), 1669 (556-4312, n = 28), and 2387 (188-6736, n = 28) ng.h/mL in the second trimester, the third trimester, and postpartum, respectively (P < 0.05 for either trimester vs postpartum). Median (range) C-24 were 63 (37-225, n = 17), 56 (<10-181, n = 30), and 81 (<10-299, n = 28) ng/mL (P < 0.05 for either trimester vs postpartum). High variability in pharmacokinetic parameters was observed between subjects. Median (range) cord blood/maternal concentration ratio was 0.55 (0.3-0.8, n = 21). Delivery HIV-1 RNA was <= 50 copies per milliliter in 70% and <= 400 copies per milliliter in 90% of women. C-min were significantly lower at 15 visits with detectable HIV-1 RNA compared with 61 visits with undetectable HIV-1 RNA, 29 (<10-93) vs 63 (15-200) ng/mL (P = 0.0001). C-min was below the protein binding-adjusted EC90 concentration (12.2 ng/mL) at 4 visits in 3 of 31 women (10%).
Conclusions: Rilpivirine exposure is lower during pregnancy compared with postpartum and highly variable. Ninety percent of women had minimum concentrations above the protein binding-adjusted EC90 for rilpivirine.
C1 [Tran, Anna H.] Univ Calif San Diego, Skaggs Sch Pharm & Pharmaceut Sci, San Diego, CA 92103 USA.
[Best, Brookie M.; Capparelli, Edmund V.] Univ Calif San Diego, Dept Pediat, Skaggs Sch Pharm & Pharmaceut Sci, Rady Childrens Hosp, San Diego, CA 92103 USA.
[Stek, Alice] Univ So Calif, Dept Obstet & Gynecol, Los Angeles, CA 90089 USA.
[Wang, Jiajia; Shapiro, David E.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
[Burchett, Sandra K.] Childrens Hosp Boston, Dept Med, Boston, MA USA.
[Kreitchmann, Regis] Irmandade Santa Casa de Misericordia Porto Alegre, HIV AIDS Res Dept, Porto Alegre, RS, Brazil.
[Rungruengthanakit, Kittipong] Chiang Mai Univ, Res Inst Hlth Sci, Chiang Mai 50000, Thailand.
[George, Kathleen] FHI 360, IMPAACT Operat Off, Durham, NC USA.
[Cressey, Tim R.] Chiang Mai Univ, Program HIV Prevent & Treatment, Dept Med Technol, Fac Associated Med Sci, Chiang Mai 50000, Thailand.
[Chakhtoura, Nahida] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, DHHS, Bethesda, MD USA.
[Smith, Elizabeth] NIAID, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Mirochnick, Mark] Boston Univ, Sch Med, Dept Pediat, Boston, MA 02118 USA.
RP Best, BM (reprint author), Univ Calif San Diego, Skaggs Sch Pharm & Pharmaceut Sci, Dept Pediat, Rady Childrens Hosp San Diego, 9500 Gilman Dr,MC 0657, La Jolla, CA 92093 USA.
EM brookie@ucsd.edu
FU National Institute of Allergy and Infectious Diseases (NIAID) of the
National Institutes of Health (NIH) [UM1AI068632, UM1AI068616,
UM1AI106716]; Eunice Kennedy Shriver National Institute of Child Health
and Human Development (NICHD); National Institute of Mental Health
(NIMH); Eunice Kennedy Shriver National Institute of Child Health and
Human Development [T35HD064385]; ViiV; Merck
FX Overall support for the International Maternal Pediatric Adolescent AIDS
Clinical Trials Group (IMPAACT) was provided by the National Institute
of Allergy and Infectious Diseases (NIAID) of the National Institutes of
Health (NIH) under Award numbers UM1AI068632 (IMPAACT LOC), UM1AI068616
(IMPAACT SDMC), and UM1AI106716 (IMPAACT LC), with cofunding from the
Eunice Kennedy Shriver National Institute of Child Health and Human
Development (NICHD) and the National Institute of Mental Health (NIMH).
A.T. was supported by the Eunice Kennedy Shriver National Institute of
Child Health and Human Development award number T35HD064385. The content
is solely the responsibility of the authors and does not necessarily
represent the official views of the NIH.; M.M. is a member of a DSMB for
studies funded by ViiV and Merck and is a member of an advisory board
for Merck. The authors have no funding or conflicts of interest to
disclose.
NR 27
TC 2
Z9 2
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1525-4135
EI 1077-9450
J9 JAIDS-J ACQ IMM DEF
JI JAIDS
PD JUL 1
PY 2016
VL 72
IS 3
BP 289
EP 296
PG 8
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA DO8UM
UT WOS:000378059800015
PM 26918544
ER
PT J
AU Gross, C
Akoth, E
Price, A
Kattakuzhy, S
Silk, R
Rosenthal, E
AF Gross, Chloe
Akoth, Elizabeth
Price, Angie
Kattakuzhy, Sarah
Silk, Rachel
Rosenthal, Elana
TI HIV/HCV Co-infection: Overcoming Barriers to Treatment
SO JANAC-JOURNAL OF THE ASSOCIATION OF NURSES IN AIDS CARE
LA English
DT Article
DE direct-acting antivirals; HCV; HIV; managed care organizations;
sustained virologic response; underserved population
ID HEPATITIS-C
AB A critical step in the eradication of hepatitis C virus (HCV) infection is access to effective therapy. With the advent of interferon-free regimens, HCV providers and patients gained hope that the success seen in clinical trials could be translated to the real world. However, the exorbitant cost of the new direct-acting antivirals limits access to these medications to the general HCV population, especially underserved patients with public insurance. We used a descriptive qualitative approach to detail the measures necessary and challenges faced by an inner-city nursing team in Washington, DC to obtain the new direct-acting antivirals. Significant time and dedication on the part of providers and staff was required to assist patients with the process of obtaining direct-acting antivirals. Copyright (C) 2016 Association of Nurses in AIDS Care
C1 [Gross, Chloe; Akoth, Elizabeth; Price, Angie; Silk, Rachel] Univ Maryland, Sch Med, Inst Human Virol, Baltimore, MD 21201 USA.
[Gross, Chloe; Akoth, Elizabeth; Price, Angie; Kattakuzhy, Sarah; Silk, Rachel] NIH, Bldg 10, Bethesda, MD 20892 USA.
[Kattakuzhy, Sarah] Univ Maryland, Sch Med, Div Infect Dis, Inst Human Virol, Baltimore, MD 21201 USA.
[Rosenthal, Elana] Leidos Biomed Res Inc, Clin Monitoring Res Program, Bethesda, MD USA.
RP Gross, C (reprint author), Univ Maryland, Sch Med, Inst Human Virol, Baltimore, MD 21201 USA.; Gross, C (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA.
EM chloe.gross@nih.gov
OI Rosenthal, Elana/0000-0001-7234-4871
NR 13
TC 0
Z9 0
U1 1
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1055-3290
EI 1552-6917
J9 J ASSOC NURSE AIDS C
JI J. Assoc. Nurses Aids Care
PD JUL-AUG
PY 2016
VL 27
IS 4
BP 524
EP 529
DI 10.1016/j.jana.2016.02.009
PG 6
WC Nursing
SC Nursing
GA DO4WK
UT WOS:000377785400017
PM 26996983
ER
PT J
AU Scheidweiler, KB
Newmeyer, MN
Barnes, AJ
Huestis, MA
AF Scheidweiler, Karl B.
Newmeyer, Matthew N.
Barnes, Allan J.
Huestis, Marilyn A.
TI Quantification of cannabinoids and their free and glucuronide
metabolites in whole blood by disposable pipette extraction and liquid
chromatography-tandem mass spectrometry
SO JOURNAL OF CHROMATOGRAPHY A
LA English
DT Article
DE Cannabinoids; Whole blood; Recent use markers; Disposable pipette
extraction
ID SOLID-PHASE EXTRACTION; CONTROLLED SMOKED CANNABIS; GAS-CHROMATOGRAPHY;
DELTA-9-TETRAHYDROCANNABINOLIC ACID; ORAL FLUID; LC-MS/MS; HUMAN URINE;
GC-MS; DELTA(9)-TETRAHYDROCANNABINOL; TETRAHYDROCANNABINOL
AB Identifying recent cannabis intake is confounded by prolonged cannabinoid excretion in chronic frequent cannabis users. We previously observed detection times <= 2.1 h for cannabidiol (CBD) and cannabinol (CBN) and Delta(9)-tetrahydrocannabinol (THC)-glucuronide in whole blood after smoking, suggesting their applicability for identifying recent intake. However, whole blood collection may not occur for up to 4h during driving under the influence of drugs investigations, making a recent-use marker with a 6-8 h detection window helpful for improving whole blood cannabinoid interpretation. Other minor cannabinoids cannabigerol (CBG), Delta 9-tetrahydrocannabivarin (THCV), and its metabolite 11-nor-9-carboxy-THCV (THCVCOOH) might also be useful. We developed and validated a sensitive and specific liquid chromatography-tandem mass spectrometry method for quantification of THC, its phase I and glucuronide phase II metabolites, and 5 five minor cannabinoids. Cannabinoids were extracted from 200 mu L whole blood via disposable pipette extraction, separated on a C-18 column, and detected via electrospray ionization in negative mode with scheduled multiple reaction mass spectrometric monitoring. Linear ranges were 0.5-100 mu g/L for THC and 11-nor-9-carboxy-THC (THCCOOH); 0.5-50 mu g/L for 11-hydroxy-THC (11-OH-THC), CBD, CBN, and THC-glucuronide; 1-50 mu g/L for CBG, THCV, and THCVCOOH; and 5-500 mu g/L for THCCOOH-glucuronide. Inter-day accuracy and precision at low, mid and high quality control (QC) concentrations were 95.1-113% and 2.4-8.5%, respectively (n =25). Extraction recoveries and matrix effects at low and high QC concentrations were 54.0-84.4% and -25.8-30.6%, respectively. By simultaneously monitoring multiple cannabinoids and metabolites, identification of recent cannabis administration or discrimination between licit medicinal and illicit recreational cannabis use can be improved. Published by Elsevier B.V.
C1 [Scheidweiler, Karl B.; Newmeyer, Matthew N.; Barnes, Allan J.; Huestis, Marilyn A.] NIDA, Chem & Drug Metab Sect, IRP, NIH, Baltimore, MD 21224 USA.
[Newmeyer, Matthew N.] Univ Maryland, Toxicol Program, Baltimore, MD 21201 USA.
RP Scheidweiler, KB (reprint author), NIDA, Chem & Drug Metab, Intramural Res Program, NIH, 251 Bayview Blvd,Suite 200 Room 05A-721, Baltimore, MD 21224 USA.
EM KScheidweiler@intra.nida.nih.gov
OI Newmeyer, Matthew/0000-0002-0653-1553
FU Intramural Research Program of the National Institute on Drug Abuse,
National Institutes of Health
FX This research was supported by the Intramural Research Program of the
National Institute on Drug Abuse, National Institutes of Health. MNN
acknowledges the Graduate Partnership Program, NIH. The authors thank
William E. Brewer (DPX Laboratories) for his technical assistance.
NR 32
TC 2
Z9 2
U1 13
U2 31
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0021-9673
EI 1873-3778
J9 J CHROMATOGR A
JI J. Chromatogr. A
PD JUL 1
PY 2016
VL 1453
BP 34
EP 42
DI 10.1016/j.chroma.2016.05.024
PG 9
WC Biochemical Research Methods; Chemistry, Analytical
SC Biochemistry & Molecular Biology; Chemistry
GA DP0MB
UT WOS:000378182800004
PM 27236483
ER
PT J
AU Kitson, AP
Metherel, AH
Chen, CT
Domenichiello, AF
Trepanier, MO
Berger, A
Bazinet, RP
AF Kitson, Alex P.
Metherel, Adam H.
Chen, Chuck T.
Domenichiello, Anthony F.
Trepanier, Marc-Olivier
Berger, Alvin
Bazinet, Richard P.
TI Effect of dietary docosahexaenoic acid (DHA) in phospholipids or
triglycerides on brain DHA uptake and accretion
SO JOURNAL OF NUTRITIONAL BIOCHEMISTRY
LA English
DT Article
DE Docosahexaenoic acid; Brain; Triacylglycerol; Phospholipid; Serum;
Uptake
ID POLYUNSATURATED FATTY-ACIDS; POSTMORTEM ORBITOFRONTAL CORTEX; MAJOR
DEPRESSIVE DISORDER; ALPHA-LINOLENIC ACID; DENSITY-LIPOPROTEIN RECEPTOR;
CAPILLARY ENDOTHELIAL-CELLS; COMPARING KRILL OIL; FISH-OIL; RAT-BRAIN;
ALZHEIMERS-DISEASE
AB Tracer studies suggest that phospholipid DHA (PL-DHA) more effectively targets the brain than triglyceride DHA (TAG-DHA), although the mechanism and whether this translates into higher brain DHA concentrations are not clear. Rats were gavaged with [U-H-3]PL-DHA and [U-H-3]TAG-DHA and blood sampled over 6 h prior to collection of brain regions and other tissues. In another experiment, rats were supplemented for 4 weeks with TAG-DHA (fish oil), PL-DHA (roe PL) or a mixture of both for comparison to a low-omega-3 diet. Brain regions and other tissues were collected, and blood was sampled weekly. DHA accretion rates were estimated using the balance method. [U-H-3]PL-DHA rats had higher radioactivity in cerebellum, hippocampus and remainder of brain, with no differences in other tissues despite higher serum lipid radioactivity in [U-H-3]TAG-DHA rats. TAG-DHA, PL-DHA or a mixture were equally effective at increasing brain DHA. There were no differences between DHA-supplemented groups in brain region, whole-body, or tissue DHA accretion rates except heart and serum TAG where the PL-DHA/TAG-DHA blend was higher than TAG-DHA. Apparent DHA beta-oxidation was not different between DHA-supplemented groups. This indicates that more labeled DHA enters the brain when consumed as PL; however, this may not translate into higher brain DHA concentrations. (C) 2016 The Authors. Published by Elsevier Inc.
C1 [Kitson, Alex P.; Metherel, Adam H.; Chen, Chuck T.; Domenichiello, Anthony F.; Trepanier, Marc-Olivier; Bazinet, Richard P.] Univ Toronto, Dept Nutr Sci, Fitzgerald Bldg,150 Coll St Room 306, Toronto, ON M5S 3E2, Canada.
[Berger, Alvin] Arctic Nutr AS, NO-6155 Orsta, Norway.
[Berger, Alvin] Univ Minnesota, Dept Food Sci & Nutr, St Paul, MN 55108 USA.
[Chen, Chuck T.] NIAAA, NIH, Bethesda, MD 20892 USA.
RP Bazinet, RP (reprint author), Univ Toronto, Dept Nutr Sci, Fitzgerald Bldg,150 Coll St Room 306, Toronto, ON M5S 3E2, Canada.
EM richard.bazinet@utoronto.ca
FU Arctic Nutrition AS, Orsta, Norway [NO-6155]; Canadian Institutes of
Health Research
FX This work was funded by Arctic Nutrition AS, NO-6155 Orsta, Norway.
Funding source was involved in study design, but not in analysis, data
handling or manuscript preparation. Alex P. Kitson received a fellowship
from the Canadian Institutes of Health Research. Richard P. Bazinet
holds a Canada Research Chair in Brain Lipid Metabolism.
NR 95
TC 2
Z9 2
U1 8
U2 16
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0955-2863
EI 1873-4847
J9 J NUTR BIOCHEM
JI J. Nutr. Biochem.
PD JUL
PY 2016
VL 33
BP 91
EP 102
DI 10.1016/j.jnutbio.2016.02.009
PG 12
WC Biochemistry & Molecular Biology; Nutrition & Dietetics
SC Biochemistry & Molecular Biology; Nutrition & Dietetics
GA DO8CY
UT WOS:000378011400011
PM 27135386
ER
PT J
AU Katz, JL
Hiranita, T
Kopajtic, TA
Rice, KC
Mesangeau, C
Narayanan, S
Abdelazeem, AH
McCurdy, CR
AF Katz, Jonathan L.
Hiranita, Takato
Kopajtic, Theresa A.
Rice, Kenner C.
Mesangeau, Christophe
Narayanan, Sanju
Abdelazeem, Ahmed H.
McCurdy, Christopher R.
TI Blockade of Cocaine or sigma Receptor Agonist Self Administration by
Subtype-Selective sigma Receptor Antagonists
SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
LA English
DT Article
ID ANTIPSYCHOTIC-DRUGS; PGRMC1 PROTEIN; HIGH-AFFINITY; DOPAMINE; RATS;
BINDING; LIGANDS; INHIBITION; ANALOGS
AB The identification of sigma receptor (sigma R) subtypes has been based on radioligand binding and, despite progress with sigma R-1 cellular function, less is known about sigma R subtype functions in vivo. Recent findings that cocaine self administration experience will trigger sigma R agonist self administration was used in this study to assess the in vivo receptor subtype specificity of the agonists (+)-pentazocine, PRE-084 [2-(4-morpholinethyl) 1-phenylcyclohexanecarboxylate hydrochloride], and 1,3-di-o-tolylguanidine (DTG) and several novel putative sigma R antagonists. Radioligand binding studies determined in vitro sigma R selectivity of the novel compounds, which were subsequently studied for self administration and antagonism of cocaine, (+)-pentazocine, PRE-084, or DTG self administration. Across the dose ranges studied, none of the novel compounds were self administered, nor did they alter cocaine self administration. All compounds blocked DTG self administration, with a subset also blocking (+)-pentazocine and PRE-084 self administration. The most selective of the compounds in binding sigma 1Rs blocked cocaine self administration when combined with a dopamine transport inhibitor, either methylphenidate or nomifensine. These drug combinations did not decrease rates of responding maintained by food reinforcement. In contrast, the most selective of the compounds in binding sigma 2Rs had no effect on cocaine self administration in combination with either dopamine transport inhibitor. Thus, these results identify subtype-specific in vivo antagonists, and the utility of sigma R agonist substitution for cocaine self administration as an assay capable of distinguishing sigma R subtype selectivity in vivo. These results further suggest that effectiveness of dual sigma R antagonism and dopamine transport inhibition in blocking cocaine self administration is specific for sigma 1Rs and further support this dual targeting approach to development of cocaine antagonists.
C1 [Katz, Jonathan L.; Hiranita, Takato; Kopajtic, Theresa A.] NIDA, Psychobiol Sect, Intramural Res Program, NIH, 251 Bayview Blvd,Suite 200, Baltimore, MD 21224 USA.
[Rice, Kenner C.] NIDA, Drug Design & Synth Sect, Intramural Res Program, NIH, Baltimore, MD USA.
[Rice, Kenner C.] NIAAA, Baltimore, MD USA.
[Mesangeau, Christophe; Narayanan, Sanju; Abdelazeem, Ahmed H.; McCurdy, Christopher R.] Univ Mississippi, Sch Pharm, Dept Biomol Sci, University, MS 38677 USA.
RP Katz, JL (reprint author), NIDA, Psychobiol Sect, Intramural Res Program, NIH, 251 Bayview Blvd,Suite 200, Baltimore, MD 21224 USA.
EM jkatz@intra.nida.nih.gov
FU National Institutes of Health National Institute on Drug Abuse
[R01-DA023205]; National Institutes of Health National Institute of
General Medical Sciences [P20-GM104932]; Intramural Research Program of
the National Institutes of Health National Institute on Drug Abuse;
National Institute on Alcohol Abuse and Alcoholism
FX This research was supported by the National Institutes of Health
National Institute on Drug Abuse [Grant R01-DA023205 (to C.R.M.)] and
the National Institutes of Health National Institute of General Medical
Sciences [Grant P20-GM104932 (to C.R.M.)]. This research was supported
[in part] by the Intramural Research Program of the National Institutes
of Health National Institute on Drug Abuse and the National Institute on
Alcohol Abuse and Alcoholism.
NR 37
TC 1
Z9 1
U1 2
U2 3
PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA
SN 0022-3565
EI 1521-0103
J9 J PHARMACOL EXP THER
JI J. Pharmacol. Exp. Ther.
PD JUL
PY 2016
VL 358
IS 1
BP 109
EP 124
DI 10.1124/jpet.116.232728
PG 16
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA DO3OQ
UT WOS:000377691300013
PM 27189970
ER
PT J
AU Chelluri, R
Kilchevsky, A
George, AK
Sidana, A
Frye, TP
Su, D
Fascelli, M
Ho, R
Abboud, SF
Turkbey, B
Merino, MJ
Choyke, PL
Wood, BJ
Pinto, PA
AF Chelluri, Raju
Kilchevsky, Amichai
George, Arvin K.
Sidana, Abhinav
Frye, Thomas P.
Su, Daniel
Fascelli, Michele
Ho, Richard
Abboud, Steven F.
Turkbey, Baris
Merino, Maria J.
Choyke, Peter L.
Wood, Bradford J.
Pinto, Peter A.
TI Prostate Cancer Diagnosis on Repeat Magnetic Resonance
Imaging-Transrectal Ultrasound Fusion Biopsy of Benign Lesions:
Recommendations for Repeat Sampling
SO JOURNAL OF UROLOGY
LA English
DT Article
DE prostatic neoplasms; magnetic resonance imaging; ultrasound,
high-intensity focused, transrectal; image-guided biopsy; watchful
waiting
ID GUIDED BIOPSY; MULTIPARAMETRIC MRI; ACTIVE SURVEILLANCE;
NATURAL-HISTORY; NEGATIVE BIOPSY; FOLLOW-UP; PATHOLOGY; RISK
AB Purpose: Urologists face a dilemma when a lesion identified on multiparametric magnetic resonance imaging is benign on image guided fusion biopsy. We investigated the detection rate of prostate cancer on repeat fusion biopsy in multiparametric magnetic resonance imaging lesions initially found to be pathologically benign on fusion biopsy.
Materials and Methods: We reviewed the records of all patients from 2007 to 2014 who underwent multiparametric magnetic resonance imaging and image guided fusion biopsy. We identified men who underwent rebiopsy of the same discrete lesion after initial fusion biopsy results were benign. Data were documented on a per lesion basis. We manually reviewed UroNav system (Invivo, Gainesville, Florida) needle tracking to verify accurate image registration. Multivariate analysis was used to identify clinical and imaging factors predictive of prostate cancer detection at repeat fusion biopsy.
Results: A total of 131 unique lesions were rebiopsied in 90 patients. Of these 131 resampled lesions 21 (16%) showed prostate cancer, which in 13 (61.9%) was Gleason 3 + 3. On multivariate analysis only lesion growth on repeat multiparametric magnetic resonance imaging was significantly associated with prostate cancer detection at repeat biopsy (HR 3.274, 95% CI 1.205-8.896, p = 0.02).
Conclusions: Pathologically benign multiparametric magnetic resonance imaging lesions on initial image guided fusion biopsy are rarely found to harbor clinically significant prostate cancer on repeat biopsy. When prostate cancer was identified, most disease was low risk. An increase in lesion diameter was an independent predictor of prostate cancer detection. While these data are retrospective, they may provide some confidence in the reliability of negative initial image guided fusion biopsies despite a positive multiparametric magnetic resonance imaging finding.
C1 [Chelluri, Raju; Kilchevsky, Amichai; George, Arvin K.; Sidana, Abhinav; Frye, Thomas P.; Su, Daniel; Fascelli, Michele; Ho, Richard; Abboud, Steven F.; Pinto, Peter A.] NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA.
[Turkbey, Baris; Choyke, Peter L.] NCI, Mol Imaging Program, NIH, Bethesda, MD 20892 USA.
[Merino, Maria J.] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA.
[Wood, Bradford J.] NCI, Ctr Intervent Oncol, NIH, Bethesda, MD 20892 USA.
RP Pinto, PA (reprint author), NCI, Urol Oncol Branch, Ctr Canc Res, 9000 Rockville Pike,Bldg 10,Room 1-5940, Bethesda, MD 20892 USA.
EM pintop@mail.nih.gov
NR 24
TC 3
Z9 3
U1 1
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0022-5347
EI 1527-3792
J9 J UROLOGY
JI J. Urol.
PD JUL
PY 2016
VL 196
IS 1
BP 62
EP 67
DI 10.1016/j.juro.2016.02.066
PG 6
WC Urology & Nephrology
SC Urology & Nephrology
GA DO7HY
UT WOS:000377954400023
PM 26880408
ER
PT J
AU Yang, CC
Weinfurt, KP
Merion, RM
Kirkali, Z
AF Yang, Claire C.
Weinfurt, Kevin P.
Merion, Robert M.
Kirkali, Ziya
CA LURN Study Grp
TI Symptoms of Lower Urinary Tract Dysfunction Research Network
SO JOURNAL OF UROLOGY
LA English
DT Article
DE lower urinary tract symptoms; research; government agencies
ID OVERACTIVE BLADDER; INCONTINENCE; WOMEN; MEN
AB Purpose: To address gaps in understanding and treating lower urinary tract symptoms, the NIDDK created the Symptoms of Lower Urinary Tract Dysfunction Research Network (LURN). The goals of LURN are to work collaboratively to 1) identify and explain the important subtypes of lower urinary tract symptoms; 2) improve the measurement of patient experiences of lower urinary tract symptoms; 3) disseminate novel findings to researchers, clinicians and patients; and 4) generate data, research tools and biological samples for future studies.
Materials and Methods: As a first step in understanding subtypes of lower urinary tract symptoms, LURN will focus on disorders of urinary sensation (eg urgency) and their causes. These are being examined with respect to patient experience, organism or systemic factors, genitourinary organs and tissues, and cellular/molecular factors. This is being achieved via an observational cohort study that is currently enrolling patients with lower urinary tract symptoms (target number 1,000) and that will extensively characterize patients with lower urinary tract symptoms. Future studies embedded within the observational cohort study will focus on neuroimaging and sensory testing, biomarkers and organ based factors. To advance the science of measurement of lower urinary tract symptoms, LURN is also developing and evaluating a comprehensive set of self-report questions to provide more granular assessments of lower urinary tract symptoms.
Results: LURN has taken its first steps by developing a framework for studying lower urinary tract symptom subtypes.
Conclusions: In developing this framework, LURN is choosing an initial domain on which to focus (sensory experiences), and creating and executing protocols designed to improve measurement of self-reported symptoms and identify patient subtypes.
C1 [Yang, Claire C.] Univ Washington, Dept Urol, Seattle, WA 98195 USA.
[Weinfurt, Kevin P.] Duke Univ, Dept Psychiat & Behav Sci, Durham, NC USA.
[Merion, Robert M.] Univ Michigan, Arbor Res Collaborat Hlth, Ann Arbor, MI 48109 USA.
[Merion, Robert M.] Univ Michigan, Dept Surg, Ann Arbor, MI 48109 USA.
[Kirkali, Ziya] NIDDK, NIH, Bethesda, MD 20892 USA.
RP Kirkali, Z (reprint author), Div Kidney Urol & Hematol, Two Democracy Plaza,Room 627,6707 Democracy Blvd, Bethesda, MD 20892 USA.
EM ziya.kirkali@nih.gov
OI Flynn, Kathryn/0000-0002-4427-3583
FU Intramural NIH HHS [Z99 DK999999]; NIDDK NIH HHS [U01 DK097776, K12
DK100024, U01 DK097772, U01 DK097779, U01 DK097780, U01 DK099879, U01
DK099932, U01 DK100011, U01 DK100017]
NR 12
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0022-5347
EI 1527-3792
J9 J UROLOGY
JI J. Urol.
PD JUL
PY 2016
VL 196
IS 1
BP 146
EP 152
DI 10.1016/j.juro.2016.01.007
PG 7
WC Urology & Nephrology
SC Urology & Nephrology
GA DO7HY
UT WOS:000377954400063
PM 26784646
ER
PT J
AU Osafo, C
Raji, YR
Olanrewaju, T
Mamven, M
Arogundade, F
Ajayi, S
Ulasi, I
Salako, B
Plange-Rhule, J
Mengistu, Y
Mc'Ligeyo, SO
Moturi, G
Winkler, CA
Moxey-Mims, MM
Rasooly, RS
Kimmel, P
Adu, D
Ojo, A
Parekh, RS
AF Osafo, Charlotte
Raji, Yemi R.
Olanrewaju, Timothy
Mamven, Manmak
Arogundade, Fatiu
Ajayi, Samuel
Ulasi, Ifeoma
Salako, Babatunde
Plange-Rhule, Jacob
Mengistu, Yewondwossen
Mc'Ligeyo, S. O.
Moturi, George
Winkler, Cheryl A.
Moxey-Mims, Marva M.
Rasooly, Rebekah S.
Kimmel, Paul
Adu, Dwomoa
Ojo, Akinlolu
Parekh, Rulan S.
CA H3Africa Kidney Disease Res
TI Genomic approaches to the burden of kidney disease in Sub-Saharan
Africa: the Human Heredity and Health in Africa (H3Africa) Kidney
Disease Research Network
SO KIDNEY INTERNATIONAL
LA English
DT News Item
DE Africa; APOL 1; chronic kidney disease; genomics
ID APOL1 RISK VARIANTS
C1 [Osafo, Charlotte; Adu, Dwomoa] Univ Ghana, Sch Med & Dent, Accra, Ghana.
[Raji, Yemi R.; Salako, Babatunde] Univ Ibadan, Dept Med, Ibadan, Nigeria.
[Olanrewaju, Timothy] Univ Ilorin, Dept Med, Ilorin, Nigeria.
[Mamven, Manmak; Ajayi, Samuel] Univ Abuja, Dept Med, Teaching Hosp, Abuja, Nigeria.
[Arogundade, Fatiu] Obafemi Awolowo Univ, Dept Med, Ife, Nigeria.
[Ulasi, Ifeoma] Univ Nigeria, Dept Med, Enugu, Nigeria.
[Plange-Rhule, Jacob] Kwame Nkrumah Univ Sci & Technol, Dept Med, Kumasi, Ghana.
[Mengistu, Yewondwossen] Univ Addis Ababa, Dept Med, Addis Ababa, Ethiopia.
[Mc'Ligeyo, S. O.; Moturi, George] Univ Nairobi, Dept Med, Nairobi, Kenya.
[Winkler, Cheryl A.] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Moxey-Mims, Marva M.; Rasooly, Rebekah S.; Kimmel, Paul] NIDDK, NIH, Bethesda, MD 20892 USA.
[Ojo, Akinlolu] Univ Michigan, Sch Med, Dept Med, Ann Arbor, MI 48104 USA.
[Parekh, Rulan S.] Univ Toronto, Hosp Sick Children, Dept Pediat, Univ Hlth Network, Toronto, ON M5G 1X8, Canada.
[Parekh, Rulan S.] Univ Toronto, Hosp Sick Children, Dept Med, Univ Hlth Network, Toronto, ON M5G 1X8, Canada.
RP Osafo, C (reprint author), Univ Ghana, POB 4236, Accra, Ghana.
EM ceyosafo@gmail.com
FU NHGRI NIH HHS [U54 HG006939]
NR 9
TC 3
Z9 3
U1 3
U2 6
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0085-2538
EI 1523-1755
J9 KIDNEY INT
JI Kidney Int.
PD JUL
PY 2016
VL 90
IS 1
BP 2
EP 5
DI 10.1016/j.kint.2015.12.059
PG 4
WC Urology & Nephrology
SC Urology & Nephrology
GA DO6YM
UT WOS:000377929400001
PM 27312436
ER
PT J
AU Acuna-Villaorduna, C
White, LF
Fennelly, KP
Jones-Lopez, EC
AF Acuna-Villaorduna, Carlos
White, Laura F.
Fennelly, Kevin P.
Jones-Lopez, Edward C.
TI Tuberculosis transmission: sputum vs aerosols
SO LANCET INFECTIOUS DISEASES
LA English
DT Letter
ID MYCOBACTERIUM-TUBERCULOSIS
C1 [Acuna-Villaorduna, Carlos; Jones-Lopez, Edward C.] Boston Med Ctr, Dept Med, Infect Dis Sect, Boston, MA USA.
[Acuna-Villaorduna, Carlos; Jones-Lopez, Edward C.] Boston Univ, Sch Med, Boston, MA 02118 USA.
[White, Laura F.] Boston Univ, Dept Biostat, Sch Publ Hlth, Boston, MA USA.
[Fennelly, Kevin P.] NHLBI, Pulm Clin Med Sect, Cardiovasc & Pulm Branch, Div Intramural Res, Bldg 10, Bethesda, MD 20892 USA.
[Fennelly, Kevin P.] NIH, Bldg 10, Bethesda, MD 20892 USA.
RP Jones-Lopez, EC (reprint author), Boston Med Ctr, Dept Med, Infect Dis Sect, Boston, MA USA.; Jones-Lopez, EC (reprint author), Boston Univ, Sch Med, Boston, MA 02118 USA.
EM edward.jones-lopez@bmc.org
NR 5
TC 0
Z9 0
U1 5
U2 5
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1473-3099
EI 1474-4457
J9 LANCET INFECT DIS
JI Lancet Infect. Dis.
PD JUL
PY 2016
VL 16
IS 7
BP 770
EP 771
PG 4
WC Infectious Diseases
SC Infectious Diseases
GA DP2LH
UT WOS:000378319600019
PM 27352747
ER
PT J
AU Cnops, L
van Griensven, J
Honko, AN
Bausch, DG
Sprecher, A
Hill, CE
Colebunders, R
Johnson, JC
Griffiths, A
Palacios, GF
Kraft, CS
Kobinger, G
Hewlett, A
Norwood, DA
Sabeti, P
Jahrling, PB
Formenty, P
Kuhn, JH
Arien, KK
AF Cnops, Lieselotte
van Griensven, Johan
Honko, Anna N.
Bausch, Daniel G.
Sprecher, Armand
Hill, Charles E.
Colebunders, Robert
Johnson, Joshua C.
Griffiths, Anthony
Palacios, Gustavo F.
Kraft, Colleen S.
Kobinger, Gary
Hewlett, Angela
Norwood, David A.
Sabeti, Pardis
Jahrling, Peter B.
Formenty, Pierre
Kuhn, Jens H.
Arien, Kevin K.
TI Essentials of filoviral load quantification
SO LANCET INFECTIOUS DISEASES
LA English
DT Article
ID EBOLA-VIRUS DISEASE; REVERSE TRANSCRIPTION-PCR; POINT-OF-CARE; VIRAL
LOAD; INFECTIOUS-DISEASES; HEMORRHAGIC-FEVER; MARBURG VIRUS;
SIERRA-LEONE; INTERNATIONAL STANDARD; SEXUAL TRANSMISSION
AB Quantitative measurement of viral load is an important parameter in the management of filovirus disease outbreaks because viral load correlates with severity of disease, survival, and infectivity. During the ongoing Ebola virus disease outbreak in parts of Western Africa, most assays used in the detection of Ebola virus disease by more than 44 diagnostic laboratories yielded qualitative results. Regulatory hurdles involved in validating quantitative assays and the urgent need for a rapid Ebola virus disease diagnosis precluded development of validated quantitative assays during the outbreak. Because of sparse quantitative data obtained from these outbreaks, opportunities for study of correlations between patient outcome, changes in viral load during the course of an outbreak, disease course in asymptomatic individuals, and the potential for virus transmission between infected patients and contacts have been limited. We strongly urge the continued development of quantitative viral load assays to carefully evaluate these parameters in future outbreaks of filovirus disease.
C1 [Cnops, Lieselotte; van Griensven, Johan] Inst Trop Med, Dept Clin Sci, B-2000 Antwerp, Belgium.
[Honko, Anna N.; Johnson, Joshua C.; Kuhn, Jens H.] NIAID, Integrated Res Facil Ft Detrick, Div Clin Res, NIH, Frederick, MD USA.
[Bausch, Daniel G.; Formenty, Pierre] WHO, CH-1211 Geneva, Switzerland.
[Sprecher, Armand] Medecins Sans Frontieres Operat Ctr Brussels, Brussels, Belgium.
[Hill, Charles E.] Emory Univ Hosp, Mol Diagnost Lab, 1364 Clifton Rd NE, Atlanta, GA 30322 USA.
[Colebunders, Robert] Univ Antwerp, Fac Med & Hlth Sci, Global Hlth Inst, Int Hlth Unit, B-2020 Antwerp, Belgium.
[Griffiths, Anthony] Texas Biomed Res Inst, Dept Virol & Immunol, San Antonio, TX USA.
[Palacios, Gustavo F.; Norwood, David A.] US Army, Med Res Inst Infect Dis, Frederick, MD USA.
[Kraft, Colleen S.] Emory Univ, Sch Med, Pathol & Lab Med, Atlanta, GA USA.
[Kobinger, Gary] Univ Manitoba, Publ Hlth Agcy Canada, Natl Microbiol Lab, Winnipeg, MB, Canada.
[Hewlett, Angela] Univ Nebraska Med Ctr, Omaha, NE USA.
[Sabeti, Pardis] Harvard Univ, Dept Organism & Evolutionary Biol, FAS Ctr Syst Biol, Cambridge, MA 02138 USA.
[Arien, Kevin K.] Inst Trop Med, Dept Biomed Sci, B-2000 Antwerp, Belgium.
RP Arien, KK (reprint author), Inst Trop Med, Dept Biomed Sci, B-2000 Antwerp, Belgium.
EM karien@itg.be
RI Palacios, Gustavo/I-7773-2015;
OI Palacios, Gustavo/0000-0001-5062-1938; Honko, Anna/0000-0001-9165-148X
FU Battelle Memorial Institute; US National Institute of Allergy and
Infectious Diseases (NIAID) [HHSN272200700016I]; European Union's
Horizon research and innovation programme [666094]
FX We thank Laura Bollinger (Battelle Memorial Institute, USA) for editing
this paper. The content of this publication does not necessarily reflect
the views or policies of the US Department of Health and Human Services,
the US Department of Defense, the US Department of the Army, WHO, or the
institutions and companies affiliated with the authors. This work was
funded in part through Battelle Memorial Institute's prime contract with
the US National Institute of Allergy and Infectious Diseases (NIAID)
under Contract No. HHSN272200700016I. JCJ is an employee of Battelle
Memorial Institute. A subcontractor to Battelle Memorial Institute who
performed this work is: JHK, an employee of Tunnell Government Services
Inc. LC holds an innovation mandate from the Agency for Innovation by
Science and Technology (IWT) from the Flemish Government. JVG is
supported by the European Union's Horizon 2020 research and innovation
programme (grant agreement number 666094).
NR 56
TC 2
Z9 2
U1 1
U2 6
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1473-3099
EI 1474-4457
J9 LANCET INFECT DIS
JI Lancet Infect. Dis.
PD JUL
PY 2016
VL 16
IS 7
BP E134
EP E138
DI 10.1016/S1473-3099(16)30063-9
PG 5
WC Infectious Diseases
SC Infectious Diseases
GA DP2LH
UT WOS:000378319600004
PM 27296694
ER
PT J
AU Lai, SJ
Qin, Y
Cowling, BJ
Ren, X
Wardrop, NA
Gilbert, M
Tsang, TK
Wu, P
Feng, LZ
Jiang, H
Peng, ZB
Zheng, JD
Liao, QH
Li, S
Horby, PW
Farrar, JJ
Gao, GF
Tatem, AJ
Yu, HJ
AF Lai, Shengjie
Qin, Ying
Cowling, Benjamin J.
Ren, Xiang
Wardrop, Nicola A.
Gilbert, Marius
Tsang, Tim K.
Wu, Peng
Feng, Luzhao
Jiang, Hui
Peng, Zhibin
Zheng, Jiandong
Liao, Qiaohong
Li, Sa
Horby, Peter W.
Farrar, Jeremy J.
Gao, George F.
Tatem, Andrew J.
Yu, Hongjie
TI Global epidemiology of avian influenza A H5N1 virus infection in humans,
1997-2015: a systematic review of individual case data
SO LANCET INFECTIOUS DISEASES
LA English
DT Review
ID TO-PERSON TRANSMISSION; RISK-FACTORS; A(H5N1) VIRUS; SUBTYPE H5N1;
HONG-KONG; MAINLAND CHINA; H7N9 VIRUS; EGYPT; VACCINES; VIETNAM
AB Avian influenza A H5N1 viruses have caused many, typically severe, human infections since the first human case was reported in 1997. However, no comprehensive epidemiological analysis of global human cases of H5N1 from 1997 to 2015 exists. Moreover, few studies have examined in detail the changing epidemiology of human H5N1 cases in Egypt, especially given the outbreaks since November, 2014, which have the highest number of cases ever reported worldwide in a similar period. Data on individual patients were collated from different sources using a systematic approach to describe the global epidemiology of 907 human H5N1 cases between May, 1997, and April, 2015. The number of affected countries rose between 2003 and 2008, with expansion from east and southeast Asia, then to west Asia and Africa. Most cases (67.2%) occurred from December to March, and the overall case-fatality risk was 483 (53.5%) of 903 cases which varied across geographical regions. Although the incidence in Egypt has increased dramatically since November, 2014, compared with the cases beforehand, there were no significant differences in the fatality risk, history of exposure to poultry, history of patient contact, and time from onset to hospital admission in the recent cases.
C1 [Lai, Shengjie; Qin, Ying; Ren, Xiang; Feng, Luzhao; Jiang, Hui; Peng, Zhibin; Zheng, Jiandong; Liao, Qiaohong; Li, Sa; Yu, Hongjie] Chinese Ctr Dis Control & Prevent, Div Infect Dis, Key Lab Surveillance & Early Warning Infect Dis, Beijing, Peoples R China.
[Lai, Shengjie; Wardrop, Nicola A.; Tatem, Andrew J.] Univ Southampton, Dept Geog & Environm, Southampton, Hants, England.
[Lai, Shengjie; Wardrop, Nicola A.] Flowminder Fdn, Stockholm, Sweden.
[Cowling, Benjamin J.; Tsang, Tim K.; Wu, Peng] Univ Hong Kong, Li Ka Shing Fac Med, Sch Publ Hlth, WHO Collaborating Ctr Infect Dis Epidemiol & Cont, Hong Kong, Hong Kong, Peoples R China.
[Gilbert, Marius] Univ Libre Bruxelles, Biol Control & Spatial Ecol, Brussels, Belgium.
[Gilbert, Marius] Fonds Natl Rech Sci, Brussels, Belgium.
[Horby, Peter W.; Farrar, Jeremy J.] Univ Oxford, Clin Res Unit, Wellcome Trust Major Overseas Programme, Ho Chi Minh City, Vietnam.
[Horby, Peter W.; Farrar, Jeremy J.] Univ Oxford, Dept Clin Med, Ctr Trop Med Nuffield, Oxford, England.
[Horby, Peter W.; Farrar, Jeremy J.] Singapore Infect Dis Initiat, Singapore, Singapore.
[Farrar, Jeremy J.] Univ Oxford, Churchill Hosp, Int Severe Acute Resp & Emerging Infect Consortiu, Ctr Trop Med, Oxford, England.
[Gao, George F.] Chinese Acad Sci, Inst Microbiol, Key Lab Pathogen Microbiol & Immunol, Beijing, Peoples R China.
[Gao, George F.] Chinese Ctr Dis Control & Prevent, Beijing, Peoples R China.
[Tatem, Andrew J.] NIH, Fogarty Int Ctr, Bldg 10, Bethesda, MD 20892 USA.
[Yu, Hongjie] Fudan Univ, Sch Publ Hlth, Minist Educ, Key Lab Publ Hlth Safety, Shanghai 200032, Peoples R China.
RP Yu, HJ (reprint author), Fudan Univ, Sch Publ Hlth, Minist Educ, Key Lab Publ Hlth Safety, Shanghai 200032, Peoples R China.
EM cfetpyhj@vip.sina.com
OI ren, xiang/0000-0001-5020-5838; Wu, Peng/0000-0003-1157-9401
FU National Science Fund for Distinguished Young Scholars [81525023]; US
National Institutes of Health (Comprehensive International Program for
Research on AIDS) [U19 AI51915]; Ministry of Science and Technology of
China [2012 ZX10004-201, 2014BAI13B05]; Ministry of Health of China
[201202006]; China CDCs Key Laboratory of Surveillance and Early-warning
on Infectious Disease; Harvard Center for Communicable Disease Dynamics
from the National Institute of General Medical Sciences [U54 GM088558];
Health and Medical Research Fund of the Health, Welfare and Food Bureau
of the Hong Kong Government; University Grants Committee of Hong Kong,
China [T11-705/14N]; Flowminder Foundation; University of Hong Kong; UK
Medical Research Council [MR/J012343/1]; Wellcome Trust [089276/Z/09/Z,
089276/B/09/Z]; EU FP7 project PREPARE [602525]; National Institutes of
Health National Institute of Allergy and Infectious Diseases
[U19AI089674]; Bill & Melinda Gates Foundation [OPP1106427, 1032350];
RAPIDD program of the Science and Technology Directorate, Department of
Homeland Security; Fogarty International Center, National Institutes of
Health
FX We thank staff members at county-level, district-level,
prefecture-level, and provincial-level Centers for Disease Control and
Prevention at the provinces with human H5N1 cases for providing
assistance with field investigation, administration, and data collection
in China; and staff members from WHO, the Ministry of Health of
Azerbaijan, and the Vietnam National Institute of Hygiene and
Epidemiology for assistance in coordination of data collection. This
study was supported by grants from the National Science Fund for
Distinguished Young Scholars (81525023); the US National Institutes of
Health (Comprehensive International Program for Research on AIDS grant
U19 AI51915); the Ministry of Science and Technology of China (2012
ZX10004-201, 2014BAI13B05); the Ministry of Health of China (201202006);
China CDCs Key Laboratory of Surveillance and Early-warning on
Infectious Disease; the Harvard Center for Communicable Disease Dynamics
from the National Institute of General Medical Sciences (U54 GM088558);
a commissioned grant from the Health and Medical Research Fund of the
Health, Welfare and Food Bureau of the Hong Kong Government; and the
University Grants Committee of Hong Kong, China (project number
T11-705/14N). SLa is supported by the Flowminder Foundation and the
University of Hong Kong for his postgraduate research on population
movement and infectious disease dynamics at the University of
Southampton. NAW is supported by the UK Medical Research Council
(MR/J012343/1). PWH is funded by the Wellcome Trust (grants
089276/Z/09/Z and 089276/B/09/Z) and the EU FP7 project PREPARE
(602525). AJT is supported by funding from National Institutes of Health
National Institute of Allergy and Infectious Diseases (U19AI089674); the
Bill & Melinda Gates Foundation (OPP1106427, 1032350); the RAPIDD
program of the Science and Technology Directorate, Department of
Homeland Security; and the Fogarty International Center, National
Institutes of Health. The funder of the study had no role in the study
design, data collection, data analysis, data interpretation, writing of
the report, or the decision to publish. The corresponding author had
full access to all the data in the study and had final responsibility
for the decision to submit for publication. The views expressed are
those of the authors and do not necessarily represent the policy of the
China CDC or the institutions with which the authors are affiliated.
NR 97
TC 6
Z9 7
U1 15
U2 27
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1473-3099
EI 1474-4457
J9 LANCET INFECT DIS
JI Lancet Infect. Dis.
PD JUL
PY 2016
VL 16
IS 7
BP E108
EP E118
DI 10.1016/S1473-3099(16)00153-5
PG 11
WC Infectious Diseases
SC Infectious Diseases
GA DP2LH
UT WOS:000378319600001
PM 27211899
ER
PT J
AU Baltos, JA
Paoletta, S
Nguyen, ATN
Gregory, KJ
Tosh, DK
Christopoulos, A
Jacobson, KA
May, LT
AF Baltos, Jo-Anne
Paoletta, Silvia
Nguyen, Anh T. N.
Gregory, Karen J.
Tosh, Dilip K.
Christopoulos, Arthur
Jacobson, Kenneth A.
May, Lauren T.
TI Structure-Activity Analysis of Biased Agonism at the Human Adenosine
A(3) Receptor
SO MOLECULAR PHARMACOLOGY
LA English
DT Article
ID FUNCTIONAL SELECTIVITY; INTERNATIONAL UNION; DRUG DISCOVERY; LIGANDS;
EFFICACY; SUBSTITUTIONS; NUCLEOSIDES; MODULATION; ACTIVATION;
QUANTIFICATION
AB Biased agonism at G protein-coupled receptors (GPCRs) has significant implications for current drug discovery, but molecular determinants that govern ligand bias remain largely unknown. The adenosine A3 GPCR (A(3)AR) is a potential therapeutic target for various conditions, including cancer, inflammation, and ischemia, but for which biased agonism remains largely unexplored. We now report the generation of bias "fingerprints" for prototypical ribose containing A(3)AR agonists and rigidified (N)-methanocarba 5'-N-methyluronamide nucleoside derivatives with regard to their ability to mediate different signaling pathways. Relative to the reference prototypical agonist IB-MECA, (N)-methanocarba 5'-N-methyluronamide nucleoside derivatives with significant N-6 or C2 modifications, including elongated aryl-ethynyl groups, exhibited biased agonism. Significant positive correlation was observed between the C2 substituent length (in angstrom) and bias toward cell survival. Molecular modeling suggests that extended C2 substituents on (N)-methanocarba 5'-N-methyluronamide nucleosides promote a progressive outward shift of the A(3)AR transmembrane domain 2, which may contribute to the subset of A(3)AR conformations stabilized on biased agonist binding.
C1 [Baltos, Jo-Anne; Nguyen, Anh T. N.; Gregory, Karen J.; Christopoulos, Arthur; May, Lauren T.] Monash Univ, Drug Discovery Biol, Monash Inst Pharmaceut Sci, Parkville, Vic 3052, Australia.
[Baltos, Jo-Anne; Nguyen, Anh T. N.; Gregory, Karen J.; Christopoulos, Arthur; May, Lauren T.] Monash Univ, Dept Pharmacol, Parkville, Vic 3052, Australia.
[Paoletta, Silvia; Tosh, Dilip K.; Jacobson, Kenneth A.] Natl Inst Diabet & Digest & Kidney Dis, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bethesda, MD USA.
RP May, LT (reprint author), Monash Univ, Drug Discovery Biol, 399 Royal Parade, Parkville, Vic 3052, Australia.; May, LT (reprint author), Monash Univ, Monash Inst Pharmaceut Sci, Dept Pharmacol, 399 Royal Parade, Parkville, Vic 3052, Australia.
EM lauren.may@monash.edu
RI Jacobson, Kenneth/A-1530-2009;
OI Jacobson, Kenneth/0000-0001-8104-1493; Christopoulos,
Arthur/0000-0003-4442-3294
FU National Institute of Diabetes and Digestive and Kidney Intramural
Research Program
FX The authors thank Drs. Michael Crouch and Ron Osmond for providing the
ERK 1/2 phosphorylation assay kit. K.A.J., D.K.T., and S.P. thank the
National Institute of Diabetes and Digestive and Kidney Intramural
Research Program for support.
NR 53
TC 1
Z9 1
U1 1
U2 9
PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA
SN 0026-895X
EI 1521-0111
J9 MOL PHARMACOL
JI Mol. Pharmacol.
PD JUL
PY 2016
VL 90
IS 1
BP 12
EP 22
DI 10.1124/mol.116.103283
PG 11
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA DO9EQ
UT WOS:000378087600002
PM 27136943
ER
PT J
AU Frank, GA
Shukla, S
Rao, P
Borgnia, MJ
Bartesaghi, A
Merk, A
Mobin, A
Esser, L
Earl, LA
Gottesman, MM
Xia, D
Ambudkar, SV
Subramaniam, S
AF Frank, Gabriel A.
Shukla, Suneet
Rao, Prashant
Borgnia, Mario J.
Bartesaghi, Alberto
Merk, Alan
Mobin, Aerfa
Esser, Lothar
Earl, Lesley A.
Gottesman, Michael M.
Xia, Di
Ambudkar, Suresh V.
Subramaniam, Sriram
TI Cryo-EM Analysis of the Conformational Landscape of Human P-glycoprotein
(ABCB1) During its Catalytic Cycle
SO MOLECULAR PHARMACOLOGY
LA English
DT Article
ID BINDING CASSETTE TRANSPORTER; ATP HYDROLYSIS; MULTIDRUG TRANSPORTER;
ELECTRON-MICROSCOPY; NUCLEOTIDE; EXPRESSION; TURNOVER; SYSTEM; CELLS;
STATE
AB The multidrug transporter P-glycoprotein (P-gp, ABCB1) is an ATP-dependent pump that mediates the efflux of structurally diverse drugs and xenobiotics across cell membranes, affecting drug pharmacokinetics and contributing to the development of multidrug resistance. Structural information about the conformational changes in human P-gp during the ATP hydrolysis cycle has not been directly demonstrated, although mechanistic information has been inferred from biochemical and biophysical studies conducted with P-gp and its orthologs, or from structures of other ATP-binding cassette transporters. Using single-particle cryo-electron microscopy, we report the surprising discovery that, in the absence of the transport substrate and nucleotides, human P-gp can exist in both open [nucleotide binding domains (NBDs) apart; inwardfacing] and closed (NBDs close; outward-facing) conformations. We also probe conformational states of human P-gp during the catalytic cycle, and demonstrate that, following ATP hydrolysis, P-gp transitions through a complete closed conformation to a complete open conformation in the presence of ADP.
C1 [Frank, Gabriel A.; Shukla, Suneet; Rao, Prashant; Borgnia, Mario J.; Bartesaghi, Alberto; Merk, Alan; Mobin, Aerfa; Esser, Lothar; Earl, Lesley A.; Gottesman, Michael M.; Xia, Di; Ambudkar, Suresh V.; Subramaniam, Sriram] NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bldg 37, Bethesda, MD 20892 USA.
RP Ambudkar, SV (reprint author), 37 Convent Dr,Rm 2120,MSC 4256, Bethesda, MD 20892 USA.; Subramaniam, S (reprint author), 50 South Dr,Rm 4306,MSC 8008, Bethesda, MD 20892 USA.
EM ambudkar@helix.nih.gov; ss1@nih.gov
FU Intramural Research Program of the National Institutes of Health,
National Cancer Institute, Center for Cancer Research; NIH-FEI Living
Laboratory for Structural Biology; Center for Cancer Research Center for
Molecular Microscopy
FX This work was supported by funds from the Intramural Research Program of
the National Institutes of Health, National Cancer Institute, Center for
Cancer Research, the NIH-FEI Living Laboratory for Structural Biology,
and the Center for Cancer Research Center for Molecular Microscopy.
NR 37
TC 4
Z9 4
U1 2
U2 8
PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA
SN 0026-895X
EI 1521-0111
J9 MOL PHARMACOL
JI Mol. Pharmacol.
PD JUL
PY 2016
VL 90
IS 1
BP 35
EP 41
DI 10.1124/mol.116.104190
PG 7
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA DO9EQ
UT WOS:000378087600004
PM 27190212
ER
PT J
AU Chuang, YF
An, Y
Bilgel, M
Wong, DF
Troncoso, JC
O'Brien, RJ
Breitner, JC
Ferruci, L
Resnick, SM
Thambisetty, M
AF Chuang, Y-F
An, Y.
Bilgel, M.
Wong, D. F.
Troncoso, J. C.
O'Brien, R. J.
Breitner, J. C.
Ferruci, L.
Resnick, S. M.
Thambisetty, M.
TI Midlife adiposity predicts earlier onset of Alzheimer's dementia,
neuropathology and presymptomatic cerebral amyloid accumulation
SO MOLECULAR PSYCHIATRY
LA English
DT Article
ID BODY-MASS INDEX; MILD COGNITIVE IMPAIRMENT; OLDER-ADULTS; LATE-LIFE;
MEDITERRANEAN DIET; GLOBAL BURDEN; RISK-FACTOR; AGING BLSA; DISEASE;
OBESITY
AB Understanding how midlife risk factors influence age at onset (AAO) of Alzheimer's disease (AD) may provide clues to delay disease expression. Although midlife adiposity predicts increased incidence of AD, it is unclear whether it affects AAO and severity of Alzheimer's neuropathology. Using a prospective population-based cohort, Baltimore Longitudinal Study of Aging (BLSA), this study aims to examine the relationships between midlife body mass index (BMI) and (1) AAO of AD (2) severity of Alzheimer's neuropathology and (3) fibrillar brain amyloid deposition during aging. We analyzed data on 1394 cognitively normal individuals at baseline (8643 visits; average follow-up interval 13.9 years), among whom 142 participants developed incident AD. In two subsamples of BLSA, 191 participants underwent autopsy and neuropathological assessment, and 75 non-demented individuals underwent brain amyloid imaging. Midlife adiposity was derived from BMI data at 50 years of age. We find that each unit increase in midlife BMI predicts earlier onset of AD by 6.7 months (P = 0.013). Higher midlife BMI was associated with greater Braak neurofibrillary but not CERAD (Consortium to Establish a Registry for Alzheimer's Disease) neuritic plaque scores at autopsy overall. Associations between midlife BMI and brain amyloid burden approached statistical significance. Thus, higher midlife BMI was also associated with greater fibrillar amyloid measured by global mean cortical distribution volume ratio (P = 0.075) and within the precuneus (left, P = 0.061; right, P = 0.079). In conclusion, midlife overweight predicts earlier onset of AD and greater burden of Alzheimer's neuropathology. A healthy BMI at midlife may delay the onset of AD.
C1 [Chuang, Y-F; Thambisetty, M.] NIA, Clin & Translat Neurosci Unit, Lab Behav Neurosci, NIH, Room 4B-311,251 Bayview Blvd, Baltimore, MD 21224 USA.
[Chuang, Y-F] Natl Yang Ming Univ, Inst Publ Hlth, Taipei 112, Taiwan.
[Chuang, Y-F] Far Eastern Mem Hosp, Dept Psychiat, New Taipei, Taiwan.
[An, Y.; Bilgel, M.; Ferruci, L.; Resnick, S. M.] NIA, Intramural Res Program, Baltimore, MD 21224 USA.
[Bilgel, M.] Johns Hopkins Univ, Sch Med, Dept Biomed Engn, Baltimore, MD 21205 USA.
[Wong, D. F.] Johns Hopkins Univ, Sch Med, Russell H Morgan Dept Radiol & Radiol Sci, Baltimore, MD USA.
[Wong, D. F.] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci & Neurosci, Baltimore, MD USA.
[Troncoso, J. C.] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA.
[O'Brien, R. J.] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA.
[Breitner, J. C.] Douglas Mental Hlth Univ Inst, Res Ctr, Ctr Studies Prevent Alzheimers Dis, Montreal, PQ, Canada.
RP Thambisetty, M (reprint author), NIA, Clin & Translat Neurosci Unit, Lab Behav Neurosci, NIH, Room 4B-311,251 Bayview Blvd, Baltimore, MD 21224 USA.
EM thambisettym@mail.nih.gov
FU Intramural Research Program, National Institute on Aging, National
Institutes of Health; [HHSN-260-2004-00012C]
FX We are grateful to the Baltimore Longitudinal Study of Aging
participants and neuroimaging staff for their dedication to these
studies and the staff of the Johns Hopkins University PET facility for
their assistance. This work was supported in part by research and
development contract HHSN-260-2004-00012C and the Intramural Research
Program, National Institute on Aging, National Institutes of Health.
NR 48
TC 4
Z9 4
U1 4
U2 8
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1359-4184
EI 1476-5578
J9 MOL PSYCHIATR
JI Mol. Psychiatr.
PD JUL
PY 2016
VL 21
IS 7
BP 910
EP 915
DI 10.1038/mp.2015.129
PG 6
WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry
SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry
GA DO9DX
UT WOS:000378085600007
PM 26324099
ER
PT J
AU Rennekamp, AJ
Huang, XP
Wang, Y
Patel, S
Lorello, PJ
Cade, L
Gonzales, APW
Yeh, JRJ
Caldarone, BJ
Roth, BL
Kokel, D
Peterson, RT
AF Rennekamp, Andrew J.
Huang, Xi-Ping
Wang, You
Patel, Samir
Lorello, Paul J.
Cade, Lindsay
Gonzales, Andrew P. W.
Yeh, Jing-Ruey Joanna
Caldarone, Barbara J.
Roth, Bryan L.
Kokel, David
Peterson, Randall T.
TI sigma(1) receptor ligands control a switch between passive and active
threat responses
SO NATURE CHEMICAL BIOLOGY
LA English
DT Article
ID ZEBRAFISH DANIO-RERIO; FORCED SWIMMING TEST; DEPRESSIVE-LIKE; KNOCKOUT
MICE; SCHIZOPHRENIA; FEAR; MODULATION; AGONISTS; AMYGDALA; BIOLOGY
AB Humans and many animals show 'freezing' behavior in response to threatening stimuli. In humans, inappropriate threat responses are fundamental characteristics of several mental illnesses. To identify small molecules that modulate threat responses, we developed a high-throughput behavioral assay in zebrafish (Danio rerio) and evaluated 10,000 compounds for their effects on freezing behavior. We found three classes of compounds that switch the threat response from freezing to escape-like behavior. We then screened these for binding activity across 45 candidate targets. Using target profile clustering, we identified the sigma-1 (sigma(1)) receptor as having a role in the mechanism of behavioral switching and confirmed that known ligands also disrupt freezing behavior. Furthermore, mutation of the gene encoding sigma(1) prevented the behavioral effect of escape-inducing compounds. One compound, which we call finazine, potently bound mammalian sigma(1) and altered threat-response behavior in mice. Thus, pharmacological and genetic interrogation of the freezing response revealed sigma(1) as a mediator of threat responses in vertebrates.
C1 [Rennekamp, Andrew J.; Wang, You; Patel, Samir; Cade, Lindsay; Gonzales, Andrew P. W.; Yeh, Jing-Ruey Joanna; Peterson, Randall T.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA.
[Rennekamp, Andrew J.; Wang, You; Patel, Samir; Cade, Lindsay; Gonzales, Andrew P. W.; Yeh, Jing-Ruey Joanna; Peterson, Randall T.] Massachusetts Gen Hosp, Dept Med, Charlestown, MA USA.
[Rennekamp, Andrew J.; Wang, You; Patel, Samir; Cade, Lindsay; Gonzales, Andrew P. W.; Yeh, Jing-Ruey Joanna; Peterson, Randall T.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Rennekamp, Andrew J.; Wang, You; Patel, Samir; Cade, Lindsay; Gonzales, Andrew P. W.; Peterson, Randall T.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA USA.
[Rennekamp, Andrew J.; Wang, You; Patel, Samir; Cade, Lindsay; Gonzales, Andrew P. W.; Peterson, Randall T.] Broad Inst, Cambridge, MA USA.
[Huang, Xi-Ping; Roth, Bryan L.] Univ N Carolina, NIMH, Psychoact Drug Screening Program, Chapel Hill, NC USA.
[Huang, Xi-Ping; Roth, Bryan L.] Univ N Carolina, Dept Pharmacol, Chapel Hill, NC USA.
[Lorello, Paul J.; Caldarone, Barbara J.] Brigham & Womens Hosp, Neurobehav Lab, Harvard NeuroDiscovery Ctr, 75 Francis St, Boston, MA 02115 USA.
[Lorello, Paul J.; Caldarone, Barbara J.] Brigham & Womens Hosp, Dept Neurol, 75 Francis St, Boston, MA 02115 USA.
[Roth, Bryan L.] Univ N Carolina, Eshelman Sch Pharm, Div Chem Biol & Med Chem, Chapel Hill, NC USA.
[Kokel, David] Univ Calif San Francisco, Dept Physiol, Box 0444, San Francisco, CA USA.
RP Peterson, RT (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA.; Peterson, RT (reprint author), Massachusetts Gen Hosp, Dept Med, Charlestown, MA USA.; Peterson, RT (reprint author), Harvard Univ, Sch Med, Dept Med, Boston, MA USA.; Peterson, RT (reprint author), Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA USA.; Peterson, RT (reprint author), Broad Inst, Cambridge, MA USA.
EM peterson@cvrc.mgh.harvard.edu
OI Rennekamp , Andrew /0000-0001-6174-7253
FU US National Institutes of Health (NIH) Psychoactive Drug Screening
Program [HHSN-271-2008-025C]; NIH [T32 HL 007208, R01 MH 086867, R01 GM
088040, U01 MH 105027]; Charles and Ann Sanders MGH Research Scholar
Award; Harvard NeuroDiscovery Center
FX We thank C. Brady, J.J. Colund, I.T. Helenius, Y.N. Jin and A. Nath for
helpful comments. Receptor binding profiles and Ki data were
provided by the US National Institutes of Health (NIH) Psychoactive Drug
Screening Program, contract HHSN-271-2008-025C. This work was supported
by NIH grants T32 HL 007208 (A.J.R.), R01 MH 086867 (R.T.P.), R01 GM
088040 (R.T.P.) and U01 MH 105027 (D.K. and J.-R.J.Y.); the Charles and
Ann Sanders MGH Research Scholar Award (R.T.P.); and the Harvard
NeuroDiscovery Center.
NR 37
TC 3
Z9 3
U1 5
U2 7
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1552-4450
EI 1552-4469
J9 NAT CHEM BIOL
JI Nat. Chem. Biol.
PD JUL
PY 2016
VL 12
IS 7
BP 552
EP +
DI 10.1038/NCHEMBIO.2089
PG 9
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA DO9EP
UT WOS:000378087500016
PM 27239788
ER
PT J
AU Bruni, G
Rennekamp, AJ
Velenich, A
McCarroll, M
Gendelev, L
Fertsch, E
Taylor, J
Lakhani, P
Lensen, D
Evron, T
Lorello, PJ
Huang, XP
Kolczewski, S
Carey, G
Caldarone, BJ
Prinssen, E
Roth, BL
Keiser, MJ
Peterson, RT
Kokel, D
AF Bruni, Giancarlo
Rennekamp, Andrew J.
Velenich, Andrea
McCarroll, Matthew
Gendelev, Leo
Fertsch, Ethan
Taylor, Jack
Lakhani, Parth
Lensen, Dennis
Evron, Tama
Lorello, Paul J.
Huang, Xi-Ping
Kolczewski, Sabine
Carey, Galen
Caldarone, Barbara J.
Prinssen, Eric
Roth, Bryan L.
Keiser, Michael J.
Peterson, Randall T.
Kokel, David
TI Zebrafish behavioral profiling identifies multitarget antipsychotic-like
compounds
SO NATURE CHEMICAL BIOLOGY
LA English
DT Article
ID PSYCHIATRIC DRUG DISCOVERY; LARVAL ZEBRAFISH; SMALL MOLECULES; CNS
DISORDERS; IN-VIVO; CLOZAPINE; PHENCYCLIDINE; SCHIZOPHRENIA; SEROTONIN;
DOPAMINE
AB Many psychiatric drugs act on multiple targets and therefore require screening assays that encompass a wide target space. With sufficiently rich phenotyping and a large sampling of compounds, it should be possible to identify compounds with desired mechanisms of action on the basis of behavioral profiles alone. Although zebrafish (Danio rerio) behavior has been used to rapidly identify neuroactive compounds, it is not clear what types of behavioral assays would be necessary to identify multitarget compounds such as antipsychotics. Here we developed a battery of behavioral assays in larval zebrafish to determine whether behavioral profiles can provide sufficient phenotypic resolution to identify and classify psychiatric drugs. Using the antipsychotic drug haloperidol as a test case, we found that behavioral profiles of haloperidol-treated zebrafish could be used to identify previously uncharacterized compounds with desired antipsychotic-like activities and multitarget mechanisms of action.
C1 [Bruni, Giancarlo; Rennekamp, Andrew J.; Peterson, Randall T.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA.
[Bruni, Giancarlo; Velenich, Andrea; Lensen, Dennis; Evron, Tama; Carey, Galen] Teleos Therapeut, Medford, MA USA.
[Rennekamp, Andrew J.; Peterson, Randall T.] Massachusetts Gen Hosp, Div Cardiol, Dept Med, Charlestown, MA USA.
[Rennekamp, Andrew J.; Peterson, Randall T.] Harvard Univ, Sch Med, Dept Syst Biol, Charlestown, MA USA.
[Rennekamp, Andrew J.; Peterson, Randall T.] Broad Inst, Cambridge, MA USA.
[McCarroll, Matthew; Fertsch, Ethan; Taylor, Jack; Lakhani, Parth; Kokel, David] Univ Calif San Francisco, Dept Physiol, Box 0444, San Francisco, CA USA.
[McCarroll, Matthew; Gendelev, Leo; Fertsch, Ethan; Taylor, Jack; Lakhani, Parth; Keiser, Michael J.; Kokel, David] Univ Calif San Francisco, Inst Neurodegenerat Dis, San Francisco, CA 94143 USA.
[Gendelev, Leo; Keiser, Michael J.] Univ Calif San Francisco, Dept Pharmaceut Chem, San Francisco, CA USA.
[Gendelev, Leo; Keiser, Michael J.] Univ Calif San Francisco, Dept Bioengn & Therapeut Sci, San Francisco, CA 94143 USA.
[Lorello, Paul J.; Caldarone, Barbara J.] Brigham & Womens Hosp, Neurobehav Lab, Harvard NeuroDiscovery Ctr, 75 Francis St, Boston, MA 02115 USA.
[Lorello, Paul J.; Caldarone, Barbara J.] Brigham & Womens Hosp, Dept Neurol, 75 Francis St, Boston, MA 02115 USA.
[Huang, Xi-Ping; Roth, Bryan L.] Univ N Carolina, Sch Med, Dept Pharmacol, Chapel Hill, NC USA.
[Huang, Xi-Ping; Roth, Bryan L.] Univ N Carolina, Sch Med, NIMH Psychoact Drug Screening Program, Chapel Hill, NC USA.
[Kolczewski, Sabine; Prinssen, Eric] Roche Innovat Ctr Basel, Roche Pharmaceut Res & Early Dev, Basel, Switzerland.
RP Kokel, D (reprint author), Univ Calif San Francisco, Dept Physiol, Box 0444, San Francisco, CA USA.; Kokel, D (reprint author), Univ Calif San Francisco, Inst Neurodegenerat Dis, San Francisco, CA 94143 USA.
EM david.kokel@ucsf.edu
OI Keiser, Michael/0000-0002-1240-2192; Bruni,
Giancarlo/0000-0003-2850-4633; Rennekamp , Andrew /0000-0001-6174-7253
FU US National Institutes of Health (NIH) [K01MH091449, U01MH105027,
R01AA022583, R44GM093456, T32EB009383, T32GM008284, R01MH086867,
R21MH085205]; Charles and Ann Sanders MGH Research Scholar Award; Glenn
Foundation Award for Research in Biological Mechanisms of Aging
FX We thank members of our research groups for helpful advice. This work
was supported by US National Institutes of Health (NIH) grants
K01MH091449, U01MH105027 and R01AA022583 (D.K.); R44GM093456 (M.J.K.),
T32EB009383 and T32GM008284 (L.G.) and R01MH086867 and R21MH085205
(R.T.P.); the Charles and Ann Sanders MGH Research Scholar Award
(R.T.P.); and the Glenn Foundation Award for Research in Biological
Mechanisms of Aging (D.K. and M.J.K.).
NR 52
TC 3
Z9 3
U1 6
U2 8
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1552-4450
EI 1552-4469
J9 NAT CHEM BIOL
JI Nat. Chem. Biol.
PD JUL
PY 2016
VL 12
IS 7
BP 559
EP +
DI 10.1038/NCHEMBIO.2097
PG 10
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA DO9EP
UT WOS:000378087500017
PM 27239787
ER
PT J
AU Roychoudhuri, R
Clever, D
Li, P
Wakabayashi, Y
Quinn, KM
Klebanoff, CA
Ji, Y
Sukumar, M
Eil, RL
Yu, ZY
Spolski, R
Palmer, DC
Pan, JH
Patel, SJ
Macallan, DC
Fabozzi, G
Shih, HY
Kanno, Y
Muto, A
Zhu, J
Gattinoni, L
O'Shea, JJ
Okkenhaug, K
Igarashi, K
Leonard, WJ
Restifo, NP
AF Roychoudhuri, Rahul
Clever, David
Li, Peng
Wakabayashi, Yoshiyuki
Quinn, Kylie M.
Klebanoff, Christopher A.
Ji, Yun
Sukumar, Madhusudhanan
Eil, Robert L.
Yu, Zhiya
Spolski, Rosanne
Palmer, Douglas C.
Pan, Jenny H.
Patel, Shashank J.
Macallan, Derek C.
Fabozzi, Giulia
Shih, Han-Yu
Kanno, Yuka
Muto, Akihiko
Zhu, Jun
Gattinoni, Luca
O'Shea, John J.
Okkenhaug, Klaus
Igarashi, Kazuhiko
Leonard, Warren J.
Restifo, Nicholas P.
TI BACH2 regulates CD8(+) T cell differentiation by controlling access of
AP-1 factors to enhancers
SO NATURE IMMUNOLOGY
LA English
DT Article
ID TRANSCRIPTION FACTORS; EXPRESSION ANALYSIS; MEMORY PHENOTYPE; REPRESSOR
BACH2; C-JUN; EFFECTOR; LYMPHOCYTES; GENE; DNA; ACTIVATION
AB T cell antigen receptor (TCR) signaling drives distinct responses depending on the differentiation state and context of CD8(+) T cells. We hypothesized that access of signal-dependent transcription factors (TFs) to enhancers is dynamically regulated to shape transcriptional responses to TCR signaling. We found that the TF BACH2 restrains terminal differentiation to enable generation of long-lived memory cells and protective immunity after viral infection. BACH2 was recruited to enhancers, where it limited expression of TCR-driven genes by attenuating the availability of activator protein-1 (AP-1) sites to Jun family signal-dependent TFs. In naive cells, this prevented TCR-driven induction of genes associated with terminal differentiation. Upon effector differentiation, reduced expression of BACH2 and its phosphorylation enabled unrestrained induction of TCR-driven effector programs.
C1 [Roychoudhuri, Rahul; Clever, David; Klebanoff, Christopher A.; Ji, Yun; Sukumar, Madhusudhanan; Eil, Robert L.; Yu, Zhiya; Palmer, Douglas C.; Pan, Jenny H.; Patel, Shashank J.; Fabozzi, Giulia; Gattinoni, Luca; Restifo, Nicholas P.] NCI, NIH, Bethesda, MD 20892 USA.
[Roychoudhuri, Rahul; Okkenhaug, Klaus] Babraham Inst, Lab Lymphocyte Signalling & Dev, Cambridge, England.
[Clever, David] Ohio State Univ, Coll Med, Med Scientist Training Program, Columbus, OH 43210 USA.
[Li, Peng; Spolski, Rosanne; Leonard, Warren J.] NHLBI, Lab Mol Immunol, NIH, Bldg 10, Bethesda, MD 20892 USA.
[Li, Peng; Spolski, Rosanne; Leonard, Warren J.] NHLBI, Ctr Immunol, NIH, Bldg 10, Bethesda, MD 20892 USA.
[Wakabayashi, Yoshiyuki; Zhu, Jun] NHLBI, Syst Biol Ctr, NIH, Bldg 10, Bethesda, MD 20892 USA.
[Quinn, Kylie M.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD USA.
[Macallan, Derek C.] St Georges Univ London, Inst Infect & Immun, London, England.
[Shih, Han-Yu; Kanno, Yuka; O'Shea, John J.] NIAMSD, Mol Immunol & Inflammat Branch, NIH, Bethesda, MD 20892 USA.
[Muto, Akihiko; Igarashi, Kazuhiko] Tohoku Univ, Dept Biochem, Grad Sch Med, Sendai, Miyagi 980, Japan.
[Muto, Akihiko; Igarashi, Kazuhiko] Japan Agcy Med Res & Dev, AMED CREST, Tokyo, Japan.
[Restifo, Nicholas P.] Georgetown Univ, Med Ctr, Grad Program Microbiol & Immunol, Washington, DC 20007 USA.
RP Roychoudhuri, R; Restifo, NP (reprint author), NCI, NIH, Bethesda, MD 20892 USA.; Roychoudhuri, R (reprint author), Babraham Inst, Lab Lymphocyte Signalling & Dev, Cambridge, England.; Restifo, NP (reprint author), Georgetown Univ, Med Ctr, Grad Program Microbiol & Immunol, Washington, DC 20007 USA.
EM rahul.roychoudhuri@babraham.ac.uk; restifo@nih.gov
RI Gattinoni, Luca/A-2281-2008; Roychoudhuri, Rahul/A-7442-2010; Ji,
Yun/B-7245-2009;
OI Gattinoni, Luca/0000-0003-2239-3282; Roychoudhuri,
Rahul/0000-0002-5392-1853; Ji, Yun/0000-0001-6340-7009; Igarashi,
Kazuhiko/0000-0002-2470-2475; Okkenhaug, Klaus/0000-0002-9432-4051
FU Intramural Research Program of the NCI; Intramural Research Program of
the NHLBI; Wellcome Trust/Royal Society grant [105663/Z/14/Z]; UK
Biotechnology and Biological Sciences Research Council [BB/N007794/1]
FX We thank S.A. Rosenberg, K. Hanada, K. Hirahara, K. Mousavi, H. Zare, V.
Sartorelli, N. Van Panhuys, S. Kerkar and A. Restifo for ideas and
discussion, A. Mixon and S. Farid for expertise with cell sorting,
members of the NHLBI sequencing core facility for help with sequencing,
L. Samsel for help with ImageStream imaging flow cytometry and G.
McMullen for expertise with mouse handling. Supported by the Intramural
Research Programs of the NCI and NHLBI, Wellcome Trust/Royal Society
grant 105663/Z/14/Z (R.R.) and UK Biotechnology and Biological Sciences
Research Council grant BB/N007794/1 (R.R. and K.O.).
NR 57
TC 12
Z9 12
U1 1
U2 2
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1529-2908
EI 1529-2916
J9 NAT IMMUNOL
JI Nat. Immunol.
PD JUL
PY 2016
VL 17
IS 7
BP 851
EP +
DI 10.1038/ni.3441
PG 12
WC Immunology
SC Immunology
GA DP1XR
UT WOS:000378283200018
PM 27158840
ER
PT J
AU Chatterjee, N
Shi, JX
Garcia-Closas, M
AF Chatterjee, Nilanjan
Shi, Jianxin
Garcia-Closas, Montserrat
TI Developing and evaluating polygenic risk prediction models for
stratified disease prevention
SO NATURE REVIEWS GENETICS
LA English
DT Review
ID GENOME-WIDE ASSOCIATION; BREAST-CANCER RISK; SINGLE-NUCLEOTIDE
POLYMORPHISMS; GENE-ENVIRONMENT INTERACTIONS; FAMILY-HISTORY; COMMON
SNPS; SUSCEPTIBILITY LOCI; MYOCARDIAL-INFARCTION; LEVERAGING PLEIOTROPY;
MULTIPLE-SCLEROSIS
AB Knowledge of genetics and its implications for human health is rapidly evolving in accordance with recent events, such as discoveries of large numbers of disease susceptibility loci from genome-wide association studies, the US Supreme Court ruling of the non-patentability of human genes, and the development of a regulatory framework for commercial genetic tests. In anticipation of the increasing relevance of genetic testing for the assessment of disease risks, this Review provides a summary of the methodologies used for building, evaluating and applying risk prediction models that include information from genetic testing and environmental risk factors. Potential applications of models for primary and secondary disease prevention are illustrated through several case studies, and future challenges and opportunities are discussed.
C1 [Chatterjee, Nilanjan] Johns Hopkins Univ, Dept Biostat, Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA.
[Chatterjee, Nilanjan] Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21205 USA.
[Chatterjee, Nilanjan; Shi, Jianxin; Garcia-Closas, Montserrat] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
RP Chatterjee, N (reprint author), Johns Hopkins Univ, Dept Biostat, Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA.; Chatterjee, N (reprint author), Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21205 USA.; Chatterjee, N (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
EM nilanjan@jhu.edu
FU National Cancer Institute, part of the US National Institutes of Health;
Bloomberg Distinguished Professorship endowment from Johns Hopkins
University
FX The research was supported by intramural funding from the National
Cancer Institute, which is part of the US National Institutes of Health,
and a Bloomberg Distinguished Professorship endowment from Johns Hopkins
University.
NR 113
TC 8
Z9 9
U1 13
U2 29
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1471-0056
EI 1471-0064
J9 NAT REV GENET
JI Nat. Rev. Genet.
PD JUL
PY 2016
VL 17
IS 7
BP 392
EP 406
DI 10.1038/nrg.2016.27
PG 15
WC Genetics & Heredity
SC Genetics & Heredity
GA DO9EZ
UT WOS:000378088700011
PM 27140283
ER
PT J
AU McDonald, SM
Nelson, MI
Turner, PE
Patton, JT
AF McDonald, Sarah M.
Nelson, Martha I.
Turner, Paul E.
Patton, John T.
TI Reassortment in segmented RNA viruses: mechanisms and outcomes
SO NATURE REVIEWS MICROBIOLOGY
LA English
DT Review
ID INFLUENZA-A VIRUS; GROUP C ROTAVIRUS; GENOMIC SEGMENTS; PHYLOGENETIC
ANALYSIS; BACTERIOPHAGE PHI-6; REVERSE GENETICS; RIBONUCLEOPROTEIN
COMPLEXES; POLYMERASE SUBUNITS; PACKAGING SIGNALS; BLUETONGUE VIRUS
AB Segmented RNA viruses are widespread in nature and include important human, animal and plant pathogens, such as influenza viruses and rotaviruses. Although the origin of RNA virus genome segmentation remains elusive, a major consequence of this genome structure is the capacity for reassortment to occur during co-infection, whereby segments are exchanged among different viral strains. Therefore, reassortment can create viral progeny that contain genes that are derived from more than one parent, potentially conferring important fitness advantages or disadvantages to the progeny virus. However, for segmented RNA viruses that package their multiple genome segments into a single virion particle, reassortment also requires genetic compatibility between parental strains, which occurs in the form of conserved packaging signals, and the maintenance of RNA and protein interactions. In this Review, we discuss recent studies that examined the mechanisms and outcomes of reassortment for three well-studied viral families - Cystoviridae, Orthomyxoviridae and Reoviridae - and discuss how these findings provide new perspectives on the replication and evolution of segmented RNA viruses.
C1 [McDonald, Sarah M.] Virginia Tech, Carilion Sch Med & Res Inst, 2 Riverside Circle, Roanoke, VA 24016 USA.
[McDonald, Sarah M.] Virginia Maryland Coll Vet Med, Dept Biomed Sci & Pathobiol, 205 Duck Pond Dr, Blacksburg, VA 24061 USA.
[Nelson, Martha I.] NIH, Fogarty Int Ctr, 31 Ctr Dr,MSC 2220, Bethesda, MD 20892 USA.
[Turner, Paul E.] Yale Univ, Osborn Mem Labs, Dept Ecol & Evolutionary Biol, 165 Prospect St,POB 208106, New Haven, CT 06520 USA.
[Patton, John T.] Univ Maryland, Virginia Maryland Coll Vet Med, 8075 Greenmead Dr, College Pk, MD 20742 USA.
RP McDonald, SM (reprint author), Virginia Tech, Carilion Sch Med & Res Inst, 2 Riverside Circle, Roanoke, VA 24016 USA.; McDonald, SM (reprint author), Virginia Maryland Coll Vet Med, Dept Biomed Sci & Pathobiol, 205 Duck Pond Dr, Blacksburg, VA 24061 USA.
EM mcdonaldsa@vtc.vt.edu
FU Virginia Tech Carilion School of Medicine and Research Institute; US
National Institutes of Health (NIH) [R01AI116815, R21AI113402,
R21AI119588]; US National Science Foundation BEACON Center for Study of
Evolution in Action; NIH [R01AI09164601]; University of Maryland,
College Park, USA
FX S.M.M. receives financial support from the Virginia Tech Carilion School
of Medicine and Research Institute and the US National Institutes of
Health (NIH; grants R01AI116815, R21AI113402 and R21AI119588). P.E.T.
receives financial support from the US National Science Foundation
BEACON Center for Study of Evolution in Action and the NIH (grant
R01AI09164601). J.T.P. is supported by funding from the University of
Maryland, College Park, USA.
NR 135
TC 5
Z9 5
U1 10
U2 26
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1740-1526
EI 1740-1534
J9 NAT REV MICROBIOL
JI Nat. Rev. Microbiol.
PD JUL
PY 2016
VL 14
IS 7
BP 448
EP 460
DI 10.1038/nrmicro.2016.46
PG 13
WC Microbiology
SC Microbiology
GA DO8ZD
UT WOS:000378073200010
PM 27211789
ER
PT J
AU Maynard, KR
Hill, JL
Calcaterra, NE
Palko, ME
Kardian, A
Paredes, D
Sukumar, M
Adler, BD
Jimenez, DV
Schloesser, RJ
Tessarollo, L
Lu, B
Martinowich, K
AF Maynard, Kristen R.
Hill, Julia L.
Calcaterra, Nicholas E.
Palko, Mary E.
Kardian, Alisha
Paredes, Daniel
Sukumar, Mahima
Adler, Benjamin D.
Jimenez, Dennisse V.
Schloesser, Robert J.
Tessarollo, Lino
Lu, Bai
Martinowich, Keri
TI Functional Role of BDNF Production from Unique Promoters in Aggression
and Serotonin Signaling
SO NEUROPSYCHOPHARMACOLOGY
LA English
DT Article
ID NEUROTROPHIC FACTOR TRANSCRIPTS; DEPRESSION-RELATED BEHAVIORS; ADULT-RAT
HIPPOCAMPUS; MESSENGER-RNA; DIFFERENTIAL REGULATION; SYNAPTIC
PLASTICITY; MULTIPLE PROMOTERS; SPLICE VARIANTS; VISUAL-CORTEX; BRAIN
AB Brain-derived neurotrophic factor (BDNF) regulates diverse biological functions ranging from neuronal survival and differentiation during development to synaptic plasticity and cognitive behavior in the adult. BDNF disruption in both rodents and humans is associated with neurobehavioral alterations and psychiatric disorders. A unique feature of Bdnf transcription is regulation by nine individual promoters, which drive expression of variants that encode an identical protein. It is hypothesized that this unique genomic structure may provide flexibility that allows different factors to regulate BDNF signaling in distinct cell types and circuits:This has led to the suggestion that isoforms may regulate specific BDNF-dependent functions; however, little scientific support for this idea exists. We generated four novel mutant mouse lines in which BDNF production from one of the four major promoters (I, II, IV, or VI) is selectively disrupted (Bdnf-e I, -e2,-e4, and -e6 mice) and used a comprehensive comparator approach to determine whether different Bdnf transcnpts are associated with specific BDNF-dependent molecular, cellular, and behavioral phenotypes. Bdnf-e I and -e2 mutant males displayed heightened aggression accompanied by convergent expression changes in specific genes associated with serotonin signaling. In contrast, BDNF-e4 and -e6 mutants were not aggressive but displayed impairments associated with GABAergic gene expression. Moreover, quantifications of BDNF protein in the hypothalamus, prefrontal cortex, and hippocampus revealed that individual Bdnf transcripts make differential, region specific contributions to total BDNF levels. The results highlight the biological significance of alternative Bdnf transcripts and provide evidence that individual isoforms serve distinct molecular and behavioral functions.
C1 [Maynard, Kristen R.; Hill, Julia L.; Calcaterra, Nicholas E.; Kardian, Alisha; Paredes, Daniel; Sukumar, Mahima; Adler, Benjamin D.; Jimenez, Dennisse V.; Schloesser, Robert J.; Martinowich, Keri] Lieber Inst Brain Dev, Johns Hopkins Med Campus,855 North Wolfe St, Baltimore, MD 21205 USA.
[Palko, Mary E.; Tessarollo, Lino] NCI, Frederick, MD 21701 USA.
[Schloesser, Robert J.] Sheppard Pratt Lieber Res Inst, Baltimore, MD USA.
[Lu, Bai] Tsinghua Univ, Sch Med, Beijing 100084, Peoples R China.
[Martinowich, Keri] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA.
[Martinowich, Keri] Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA.
RP Martinowich, K (reprint author), Lieber Inst Brain Dev, Johns Hopkins Med Campus,855 North Wolfe St, Baltimore, MD 21205 USA.
EM kerimartinowich@libd.org
RI Martinowich, Keri/F-9841-2012;
OI Hill, Julia/0000-0003-4744-0532
FU Lieber Institute for Brain Development; Intramural Program of the
National Institute of Mental Health; Intramural Program for the National
Cancer Institute; National Institute of Mental Health [MH105592]; Brain
and Behavior Research Foundation
FX We thank Ragini Ganjoo and Nicholas Hardy for technical assistance, and
Dr Daniel Weinberger for critical reading of the manuscript. Funding for
these studies was provided by the Lieber Institute for Brain
Development, the Intramural Program of the National Institute of Mental
Health, and the Intramural Program for the National Cancer Institute.
Additional funding awards from the National Institute of Mental Health
(PI: KM, MH105592) and the Brain and Behavior Research Foundation (PI:
KM, Young Investigator Award) partially supported these studies.
NR 59
TC 3
Z9 3
U1 9
U2 9
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0893-133X
EI 1740-634X
J9 NEUROPSYCHOPHARMACOL
JI Neuropsychopharmacology
PD JUL
PY 2016
VL 41
IS 8
BP 1943
EP 1955
DI 10.1038/npp.2015.349
PG 13
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA DO5SJ
UT WOS:000377842800002
PM 26585288
ER
PT J
AU McLaughlin, KA
Sheridan, MA
Gold, AL
Duys, A
Lambert, HK
Peverill, M
Heleniak, C
Shechner, T
Wojcieszak, Z
Pine, DS
AF McLaughlin, Katie A.
Sheridan, Margaret A.
Gold, Andrea L.
Duys, Andrea
Lambert, Hilary K.
Peverill, Matthew
Heleniak, Charlotte
Shechner, Tomer
Wojcieszak, Zuzanna
Pine, Daniel S.
TI Maltreatment Exposure, Brain Structure, and Fear Conditioning in
Children and Adolescents
SO NEUROPSYCHOPHARMACOLOGY
LA English
DT Article
ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; NEURAL DEVELOPMENT
DEPRIVATION; ANXIETY DISORDERS; STRESS REACTIVITY; CONDUCT DISORDER;
EARLY EXPERIENCE; THREAT; CORTEX; PTSD; AMYGDALA
AB Alterations in leaming processes and the neural circuitry that supports fear conditioning and extinction represent mechanisms through which trauma exposure might influence risk for psychopathology. Few studies examine how trauma or neural structure relates to fear conditioning in children. Children (n = 94) aged 6-18 years, 40.4% (n = 38) with exposure to maltreatment (physical abuse, sexual abuse, or domestic violence), completed a fear conditioning paradigm utilizing blue and yellow bells-as conditioned stimuli (CS+/CS -) and an aversive alarm noise as the unconditioned stimulus. Skin conductance responses (SCR) and self-reported fear were acquired. Magnetic resonance imaging data were acquired from 60 children. children without maltreatment exposure exhibited strong differential conditioning to the CS+ vs CS -, based on SCR and self-reported fear. In contrast, maltreated children exhibited blunted SCR to the CS+ and failed to exhibit differential SCR to the CS+ vs CS - during early conditioning. Amygdala and hippocampal volume were reduced among children with maltreatment exposure and were negatively associated with SCR to the CS+ during early conditioning in the total sample, although thdse associations were negative only among non-maltreated children and were positive among maltreated children. The association of maltreatment with externalizing psychopathology was mediated by this perturbed pattern of fear conditioning. Child maltreatment is associated with failure to discriminate between threat and safety cues during fear conditioning in children. Poor threat safety discrimination might reflect either enhanced fear generalization or a deficit in associative leaming, which may in turn represent a central mechanism underlying the development of maltreatment-related externalizing psychopathology in children.
C1 [McLaughlin, Katie A.; Duys, Andrea; Lambert, Hilary K.; Peverill, Matthew; Heleniak, Charlotte] Univ Washington, Dept Psychol, Box 351525, Seattle, WA 98195 USA.
[Sheridan, Margaret A.] Univ N Carolina, Dept Psychol, Chapel Hill, NC USA.
[Gold, Andrea L.; Pine, Daniel S.] NIMH, Sect Dev & Affect Neurosci, Bethesda, MD 20892 USA.
[Shechner, Tomer] Univ Haifa, Dept Psychol, IL-31999 Haifa, Israel.
[Wojcieszak, Zuzanna] Temple Univ, Dept Psychol, Philadelphia, PA 19122 USA.
RP McLaughlin, KA (reprint author), Univ Washington, Dept Psychol, Box 351525, Seattle, WA 98195 USA.
EM mclaughk@uw.edu
OI Gold, Andrea/0000-0003-4447-776X; McLaughlin, Katie/0000-0002-1362-2410
FU NARSAD Young Investigator Award from the Brain and Behavior Foundation;
National Institute of Mental Health [K01-MH092526, R01-MH103291,
K01-MH092555]; National Institute of Child Health and Human Development
[U54 HD083091]; Bezos Family Foundation; Intramural Research Program of
the National Institutes of Health
FX This research was supported by a NARSAD Young Investigator Award from
the Brain and Behavior Foundation to McLaughlin and grants from the
National Institute of Mental Health (K01-MH092526 and R01-MH103291 to KA
McLaughlin and K01-MH092555 to MA Sheridan), the National Institute of
Child Health and Human Development (U54 HD083091 to the University of
Washington's Center on Human Development and Disability), and the Bezos
Family Foundation to KA McLaughlin and MA Sheridan. These funders
provided support for data collection and analysis. In addition, this
research was supported in part by the Intramural Research Program of the
National Institutes of Health. Drs. McLaughlin, Sheridan, and Pine have
received compensation for activities related to teaching, editing, and
clinical care that pose no conflicts of interest. The authors declare no
conflict of interest.
NR 51
TC 4
Z9 4
U1 10
U2 19
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0893-133X
EI 1740-634X
J9 NEUROPSYCHOPHARMACOL
JI Neuropsychopharmacology
PD JUL
PY 2016
VL 41
IS 8
BP 1956
EP 1964
DI 10.1038/npp.2015.365
PG 9
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA DO5SJ
UT WOS:000377842800003
PM 26677946
ER
PT J
AU Haney, M
Malcolm, RJ
Babalonis, S
Nuzzo, PA
Cooper, ZD
Bedi, G
Gray, KM
McRae-Clarke, A
Lofwall, MR
Sparenborg, S
Walsh, SL
AF Haney, Margaret
Malcolm, Robert J.
Babalonis, Sharma
Nuzzo, Paul A.
Cooper, Ziva D.
Bedi, Gillinder
Gray, Kevin M.
McRae-Clarke, Aimee
Lofwall, Michelle R.
Sparenborg, Steven
Walsh, Sharon L.
TI Oral Cannabidiol does not Alter the Subjective, Reinforcing or
Cardiovascular Effects of Smoked Cannabis
SO NEUROPSYCHOPHARMACOLOGY
LA English
DT Article
ID NEURAL-BASIS; OROMUCOSAL SPRAY; DOUBLE-BLIND;
DELTA-9-TETRAHYDROCANNABINOL; MARIJUANA; THC; ANXIETY; PHARMACOKINETICS;
DELTA(9)-TETRAHYDROCANNABINOL; TETRAHYDROCANNABINOL
AB Cannabidiol (CBD), a constituent of cannabis with few psychoactive effects, has been reported in some studies to attenuate certain aspects of Delta(9)-tetrahydrocannabinol (THC) intoxication. However, most studies have tested only one dose of CBD in combination with one dose of oral THC, making it difficult to assess the nature of this interaction. Further, the effect of oral CBD on smoked cannabis administration is unknown. The objective of this multi-site, randomized, double-blind, within-subject laboratory study was to assess the influence of CBD (0, 200, 400, 800 mg, p.o.) pretreatment on the reinforcing, subjective, cognitive, and physiological effects of smoked cannabis (0.01 (inactive), 5.30-5.80% THC). Nbn-treatment-seeking, healthy cannabis smokers (n = 3I; 17M, 14 F) completed eight outpatient sessions. CBD was administered 90 min prior to cannabis administration. The behavioral and cardiovascular effects of cannabis were measured at baseline and repeatedly throughout the session. A subset of participants (n = 8) completed an additional session to measure' plasma CBD concentrations after administration of the highest CBD dose (800 mg). Under placebo CBD conditions, active cannabis (I) was self-administered by significantly more participants than placebo cannabis and (2) produced significant, time-dependent increases in ratings of 'High', 'Good Effect', ratings of the cannabis cigarette (eg, strength, liking), and heart rate relative to inactive cannabis. CBD, which alone produced no significant psychoactive or cardiovascular effects, did not significantly alter any of these outcomes. Cannabis self-administration, subjective effects, and cannabis ratings did not vary as a function of CBD dose relative to placebo capsules. These findings suggest that oral CBD does not reduce the reinforcing, physiological, or positive subjective effects of smoked cannabis.
C1 [Haney, Margaret; Cooper, Ziva D.; Bedi, Gillinder] New York State Psychiat Inst & Hosp, Div Subst Abuse, 1051 Riverside Dr,Unit 120, New York, NY 10032 USA.
[Haney, Margaret; Cooper, Ziva D.; Bedi, Gillinder] Columbia Univ, Med Ctr, Dept Psychiat, 1051 Riverside Dr,Unit 120, New York, NY 10032 USA.
[Malcolm, Robert J.; Gray, Kevin M.; McRae-Clarke, Aimee] Med Univ S Carolina, Charleston, SC 29425 USA.
[Babalonis, Sharma; Nuzzo, Paul A.; Lofwall, Michelle R.; Walsh, Sharon L.] Univ Kentucky, Lexington, KY USA.
[Sparenborg, Steven] NIDA, Bethesda, MD 20892 USA.
RP Haney, M (reprint author), New York State Psychiat Inst & Hosp, Div Subst Abuse, 1051 Riverside Dr,Unit 120, New York, NY 10032 USA.; Haney, M (reprint author), Columbia Univ, Med Ctr, Dept Psychiat, 1051 Riverside Dr,Unit 120, New York, NY 10032 USA.
EM mh235@columbia.edu
FU US National Institute on Drug Abuse [DA009236, U10DA013727, U10DA13732];
Insys Therapeutics; Aelis Farma; Lifeloc Technologies; Forest
Pharmaceuticals; Supernus Pharmaceuticals and Merck
FX This research was supported by the US National Institute on Drug Abuse
(DA009236, U10DA013727, U10DA13732). We also thank NIDA for supplying
the cannabis to conduct this study, and Dr Hari Singh, PhD at NIDA for
facilitating the analysis of plasma CBD concentrations by Dr David
Moody, PhD at University of Utah (NIDA contract #NO1DA-14-7788). Many
thanks to Dr Richard W Foltin (CUMC) and Dr Thomas H Kelly (UK) for
their support in conducting this study, and to the expert contributions
of Dr Adam Bisaga, Olivia Derella (CUMC), Dr Samy Claude Elayi, Tori
Votaw, and Cleeve Emurian (UK). This research was funded by NIDA. Dr
Haney has received research support from Aelis Farma and Lifeloc
Technologies, and along with Dr Cooper, has received research support
from investigator-initiated studies from Insys Therapeutics. Dr Cooper
serves as a consultant to KannaLife Sciences and PharmaCann, LLC. Dr
McRae-Clark has received research support from Forest Pharmaceuticals
(medication only). Dr Gray has received research funding from Supernus
Pharmaceuticals and Merck, for unrelated research.
NR 52
TC 1
Z9 1
U1 8
U2 14
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0893-133X
EI 1740-634X
J9 NEUROPSYCHOPHARMACOL
JI Neuropsychopharmacology
PD JUL
PY 2016
VL 41
IS 8
BP 1974
EP 1982
DI 10.1038/npp.2015.367
PG 9
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA DO5SJ
UT WOS:000377842800005
PM 26708108
ER
PT J
AU Davis, RJ
Van Waes, C
Allen, CT
AF Davis, Ruth J.
Van Waes, Carter
Allen, Clint T.
TI Overcoming barriers to effective immunotherapy: MDSCs, TAMs, and Tregs
as mediators of the immunosuppressive microenvironment in head and neck
cancer
SO ORAL ONCOLOGY
LA English
DT Article
DE Immunity; Antigenicity; Immunogenicity; Immunotherapy
ID REGULATORY T-CELLS; TUMOR-ASSOCIATED MACROPHAGES; MYELOID
SUPPRESSOR-CELLS; ANTITUMOR IMMUNE-RESPONSES; HOST ENVIRONMENT PROMOTES;
ORAL SQUAMOUS CARCINOMA; HEPATOCELLULAR-CARCINOMA; CYTOKINES IL-1-ALPHA;
DEPENDENT MECHANISM; INTERFERON-GAMMA
AB A significant subset of head and neck cancers display a T-cell inflamed phenotype, suggesting that patients with these tumors should respond to therapeutic approaches aimed at strengthening antitumor immune responses. A major barrier to the development of an effective anti-tumor immune response, at baseline or in response to immunotherapy, is the development of an immunosuppressive tumor microenvironment. Several well described mechanisms of effector immune cell suppression in the head and neck cancer microenvironment are discussed here, along with updates on current trials designed to translate what we have learned from pre-clinical and correlative clinical studies into improved responses in patients with head and neck cancer following immune activating therapies. Published by Elsevier Ltd.
C1 [Davis, Ruth J.; Van Waes, Carter; Allen, Clint T.] Natl Inst Deafness & Other Commun Disorders, Tumor Biol Sect, Head & Neck Surg Branch, NIH, Bethesda, MD USA.
[Allen, Clint T.] Johns Hopkins Sch Med, Dept Otolaryngol Head & Neck Surg, Baltimore, MD USA.
RP Allen, CT (reprint author), 10 Ctr Dr,CRC 4-2740, Bethesda, MD 20892 USA.
EM clint.allen@nih.gov
OI Davis, Ruth/0000-0001-9592-932X
FU Intramural NIH HHS [ZIA DC000087-01]; NIDCD NIH HHS [R01 DC000087]
NR 130
TC 0
Z9 0
U1 4
U2 8
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1368-8375
EI 1879-0593
J9 ORAL ONCOL
JI Oral Oncol.
PD JUL
PY 2016
VL 58
BP 59
EP 70
DI 10.1016/j.oraloncology.2016.05.002
PG 12
WC Oncology; Dentistry, Oral Surgery & Medicine
SC Oncology; Dentistry, Oral Surgery & Medicine
GA DO7AV
UT WOS:000377935500015
PM 27215705
ER
PT J
AU El-Maouche, D
Dumitrescu, CE
Andreopoulou, P
Gafni, RI
Brillante, BA
Bhattacharyya, N
Fedarko, NS
Collins, MT
AF El-Maouche, D.
Dumitrescu, C. E.
Andreopoulou, P.
Gafni, R. I.
Brillante, B. A.
Bhattacharyya, N.
Fedarko, N. S.
Collins, M. T.
TI Stability and degradation of fibroblast growth factor 23 (FGF23): the
effect of time and temperature and assay type
SO OSTEOPOROSIS INTERNATIONAL
LA English
DT Article
DE Assay; FGF23; Immutopics; Kainos; Stability
ID FAMILIAL TUMORAL CALCINOSIS; O-GLYCOSYLATION;
FIBROBLAST-GROWTH-FACTOR-23; HYPERPHOSPHATEMIA; HYPOPHOSPHATEMIA;
OSTEOMALACIA; MUTATIONS; INTACT; SERUM
AB There is growing need for a reliable assay for measuring fibroblast growth factor 23 (FGF23), a regulator of phosphorus and vitamin D. In this work, we analyze and compare the performance of three available assays, including the effect of temperature and time. This knowledge will allow for better understanding of FGF23 in the future.
Intact and C-terminal FGF23 (iFGF23 and cFGF23) concentrations are important in the diagnosis of hypo- and hyperphosphatemic diseases. The effects of temperature, storage, and specimen handling on FGF23 levels are not well known. We investigated the effects of various factors on plasma and serum measurement of FGF23 using three different assays.
Serum and plasma FGF23 were measured using three commercially available ELISA assays-two measuring iFGF23 and one measuring cFGF23. Samples from subjects with known FGF23 disorders were stored at 4, 22, and 37 A degrees C and analyzed at different intervals up to 48 hours (h). A subset of samples underwent repeated freeze-thaw cycles, and samples frozen at -80 A degrees C for up to 60 months were reanalyzed. The effect of adding a furin convertase inhibitor on FGF23 degradation was investigated using samples stored at 37 A degrees C for 48 h. Intact FGF23 levels were measured from plasma samples of four different groups to test the correlation of the two assays.
Plasma FGF23 levels were stable when stored at 4 and 22 A degrees C for 48 h. Both plasma and serum FGF23 levels demonstrated relative stability after five freeze-thaw cycles. Long-term storage at -80 A degrees C for 40 months induced some variability in FGF23 levels. The addition of a furin inhibitor did not affect FGF23 degradation. Intact FGF23 levels showed good correlation only at the upper limit of the assay range when comparing the two assays.
Sample type, handling, and choice of assay are factors that affect FGF23 levels and should be considered when measuring this hormone.
C1 [El-Maouche, D.] Univ Miami, Miller Sch Med, Dept Med, Div Endocrinol Diabet & Metab, Miami, FL 33136 USA.
[El-Maouche, D.; Gafni, R. I.; Brillante, B. A.; Collins, M. T.] Natl Inst Dent & Craniofacial Res, Skeletal Clin Studies Unit, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD USA.
[Dumitrescu, C. E.] Alice Hyde Med Ctr, Div Endocrinol, Malone, NY USA.
[Andreopoulou, P.] Hosp Special Surg, Endocrine Serv, Dept Med, 535 E 70th St, New York, NY 10021 USA.
[Bhattacharyya, N.] NCI, Thorac & GI Oncol Branch, NIH, Bethesda, MD 20892 USA.
[Fedarko, N. S.] Johns Hopkins Univ, Dept Med, Div Geriatr Med & Gerontol, Baltimore, MD USA.
RP Collins, MT (reprint author), Natl Inst Dent & Craniofacial Res, Skeletal Clin Studies Unit, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD USA.
EM mcollins@dir.nidcr.nih.gov
OI Fedarko, Neal/0000-0001-6055-6279
FU Division of Intramural Research, National Institute of Dental and
Craniofacial Research; National Center for Advancing Translational
Sciences, National Institutes of Health, Bethesda, MD
FX This study was supported by the Division of Intramural Research,
National Institute of Dental and Craniofacial Research, and the National
Center for Advancing Translational Sciences, National Institutes of
Health, Bethesda, MD.
NR 23
TC 0
Z9 0
U1 1
U2 1
PU SPRINGER LONDON LTD
PI LONDON
PA 236 GRAYS INN RD, 6TH FLOOR, LONDON WC1X 8HL, ENGLAND
SN 0937-941X
EI 1433-2965
J9 OSTEOPOROSIS INT
JI Osteoporosis Int.
PD JUL
PY 2016
VL 27
IS 7
BP 2345
EP 2353
DI 10.1007/s00198-016-3543-5
PG 9
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA DO8AQ
UT WOS:000378004800021
PM 26928188
ER
PT J
AU Filipski, KK
Pacanowski, MA
Ramamoorthy, A
Feero, WG
Freedman, AN
AF Filipski, Kelly K.
Pacanowski, Michael A.
Ramamoorthy, Anuradha
Feero, William Gregory
Freedman, Andrew N.
TI Dosing recommendations for pharmacogenetic interactions related to drug
metabolism
SO PHARMACOGENETICS AND GENOMICS
LA English
DT Article
DE biomarkers; drug labeling; drug-metabolizing enzymes; pharmacogenomics
ID EGAPP-WORKING-GROUP; IMPLEMENTATION CONSORTIUM; GUIDELINE
AB Objective Pharmacogenomic studies have established the important contribution of drug-metabolizing enzyme genotype toward drug toxicity and treatment failure; however, clinical implementation of pharmacogenomics has been slow. The aim of this study was to systematically review the information on drug-metabolizing enzyme pharmacogenomics available in the US drug labeling, practice guidelines, and recommendations.
Methods Drug-metabolizing enzyme genotype and phenotype information was assessed in US FDA drug labeling, clinical practice guidelines, and independent technology assessors to evaluate the consistency in information sources for healthcare providers.
Results Eighty four gene-drug pairs were identified as having drug-metabolizing enzyme genotype or phenotype information within the label. The manner in which pharmacogenomic information was presented was heterogeneous both within the label and between clinical practice recommendations.
Conclusion For proper implementation of pharmacogenomics in clinical practice, information sources for healthcare providers should relay consistent and clear information for the appropriate use of biomarkers. Copyright (C) 2016 Wolters Kluwer Health, Inc. All rights reserved.
C1 [Filipski, Kelly K.; Freedman, Andrew N.] NCI, Epidemiol & Genom Res Program, Div Canc Control & Populat Sci, Rockville, MD USA.
[Pacanowski, Michael A.; Ramamoorthy, Anuradha] US FDA, Off Clin Pharmacol, Ctr Drug Evaluat & Res, Silver Spring, MD USA.
[Feero, William Gregory] Maine Dartmouth Family Med Residency Program, Augusta, ME USA.
RP Filipski, KK (reprint author), 9609 Med Ctr Dr Room 4E228, Rockville, MD 20850 USA.
EM kelly.filipski@nih.gov
FU US Department of Energy; CDER
FX A.R. was supported by an appointment to the Oak Ridge Institute for
Science and Education (ORISE) Research Participation Program at the
Center for Drug Evaluation and Research administered by the ORISE
through an agreement between the US Department of Energy and CDER.
NR 22
TC 0
Z9 0
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1744-6872
EI 1744-6880
J9 PHARMACOGENET GENOM
JI Pharmacogenet. Genomics
PD JUL
PY 2016
VL 26
IS 7
BP 334
EP 339
DI 10.1097/FPC.0000000000000220
PG 6
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology
& Pharmacy
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology
& Pharmacy
GA DO3MA
UT WOS:000377684500003
PM 27058883
ER
PT J
AU Gebreab, SY
Riestra, P
Gaye, A
Khan, RJ
Xu, RH
Davis, AR
Quarells, RC
Davis, SK
Gibbons, GH
AF Gebreab, Samson Y.
Riestra, Pia
Gaye, Amadou
Khan, Rumana J.
Xu, Ruihua
Davis, Adam R.
Quarells, Rakale C.
Davis, Sharon K.
Gibbons, Gary H.
TI Perceived neighborhood problems are associated with shorter telomere
length in African American women
SO PSYCHONEUROENDOCRINOLOGY
LA English
DT Article
DE African Americans; Cellular aging; Telomere length; Psychosocial stress;
Perceived neighborhood environments
ID SOCIOECONOMIC-STATUS; OXIDATIVE STRESS; HEALTH BEHAVIORS; MENTAL-HEALTH;
LIFE STRESS; ATHEROSCLEROSIS; DISORDER; DISEASE; DISADVANTAGE;
DISPARITIES
AB Objectives: African Americans (AA) experience higher levels of stress related to living in racially segregated and poor neighborhoods. However, little is known about the associations between perceived neighborhood environments and cellular aging among adult AA. This study examined whether perceived neighborhood environments were associated with telomere length (TL) in AA after adjustment for individual-level risk factors.
Methods: The analysis included 158 women and 75 men AA aged 30-55 years from the Morehouse School of Medicine Study. Relative TL (T/S ratio) was measured from peripheral blood leukocytes using quantitative real-time polymerase chain reaction. Multivariable linear regression models were used to examine the associations of perceived neighborhood social cohesion, problems, and overall unfavorable perceptions with log-TL.
Results: Women had significantly longer TL than men (0.59 vs. 0.54, p = 0.012). After controlling for sociodemographic, and biomedical and psychosocial factors, a 1-SD increase in perceived neighborhood problems was associated with 7.3% shorter TL in women (Mean Difference [MD] = -0.073 (Standard Error = 0.03), p = 0.012). Overall unfavorable perception of neighborhood was also associated with 5.9% shorter TL among women (MD = 0.059(0.03),p = 0.023). Better perceived social cohesion were associated with 2.4% longer TL, but did not reach statistical significance (MD = 0.024(0.02), p = 0.218). No association was observed between perceived neighborhood environments and TL in men.
Conclusions: Our findings suggest that perceived neighborhood environments may be predictive of cellular aging in AA women even after accounting for individual-level risk factors. Additional research with a larger sample is needed to determine whether perceived neighborhood environments are causally related to TL. Published by Elsevier Ltd. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.orgilicensesiby-nc-nd/4.0/).
C1 [Gebreab, Samson Y.; Riestra, Pia; Gaye, Amadou; Khan, Rumana J.; Xu, Ruihua; Davis, Adam R.; Davis, Sharon K.; Gibbons, Gary H.] NHGRI, Metab Cardiovasc & Inflammatory Dis Genom Branch, Cardiovasc Sect, NIH, Bethesda, MD 20892 USA.
[Quarells, Rakale C.] Morehouse Sch Med, Community Hlth & Prevent Med, Cardiovasc Res Inst, Atlanta, GA 30310 USA.
RP Gebreab, SY (reprint author), NHGRI, NIH, Metab Cardiovasc & Inflammatory Dis Genom Branch, Cardiovasc Dis Sect,Social Epidemiol Res Unit, 10 Ctr Dr,Room 7N316,MSC 1644, Bethesda, MD 20892 USA.
EM samson.gebreab@nih.gov
OI Gaye, Amadou/0000-0002-1180-2792
FU Intramural Program of National Human Genomics Institute, National
Institutes of Health; National Institute on Minority Health and Health
Disparities [1RC4MD005964-01]
FX This research is supported by Intramural Program of National Human
Genomics Institute, National Institutes of Health. The MH-GRID study was
supported by the National Institute on Minority Health and Health
Disparities (1RC4MD005964-01). We also thank Cancer Genomics Research
laboratory (CGR) for performing telomere assay for our study and we also
wish to thank Casey Dagnall for her helpful comments on telomere length
measurements.
NR 54
TC 1
Z9 1
U1 1
U2 1
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0306-4530
J9 PSYCHONEUROENDOCRINO
JI Psychoneuroendocrinology
PD JUL
PY 2016
VL 69
BP 90
EP 97
DI 10.1016/j.psyneuen.2016.03.018
PG 8
WC Endocrinology & Metabolism; Neurosciences; Psychiatry
SC Endocrinology & Metabolism; Neurosciences & Neurology; Psychiatry
GA DO4CH
UT WOS:000377728900011
PM 27070760
ER
PT J
AU Kim, EJ
Yin, XY
Fontes, JD
Magnani, JW
Lubitz, SA
McManus, DD
Seshadri, S
Vasan, RS
Ellinor, PT
Larson, MG
Benjamin, EJ
Rienstra, M
AF Kim, Eun-Jeong
Yin, Xiaoyan
Fontes, Joao D.
Magnani, Jared W.
Lubitz, Steve A.
McManus, David D.
Seshadri, Sudha
Vasan, Ramachandran S.
Ellinor, Patrick T.
Larson, Martin G.
Benjamin, Emelia J.
Rienstra, Michiel
TI Atrial fibrillation without comorbidities: Prevalence, incidence and
prognosis (from the Framingham Heart Study)
SO AMERICAN HEART JOURNAL
LA English
DT Article
ID 30-YEAR FOLLOW-UP; RISK-FACTOR; PROGRESSION; SURVIVAL; DISEASE; CURVES
AB Background The epidemiology of atrial fibrillation (AF) without comorbidities, known as 'lone AF', is uncertain. Although it has been considered a benign condition, we hypothesized that it confers a worse prognosis compared with a matched sample without AF.
Methods We described the proportion of AF without comorbidities (clinical, subclinical cardiovascular disease and triggers) among the entire AF sample in Framingham Heart Study (FHS). We compared AF without comorbidities with typical AF, and age-, sex-and cohort-matched individuals without AF, using Cox proportional hazards analysis in relation to combined cardiovascular events (stroke, heart failure, myocardial infarction), and mortality.
Results Of 10,311 FHS participants, 1,961 were diagnosed with incident AF, among which 173 individuals had AF without comorbidities (47% women, mean age 71 +/- 12 years). AF without comorbidities had a prevalence of 1.7% of the entire cohort, and an annual incidence of 0.5 per 1000 person-years. During a median follow-up of 9.7 years after initial AF, 137 individuals with AF without comorbidities (79.2%) died and 141 individuals developed cardiovascular events (81.5%). AF without comorbidities had significantly lower mortality (HR 0.67, 95% CI 0.55-0.81, P < .001) and total cardiovascular events (HR 0.66, 95% CI 0.55-0.80, P < .001) compared with typical AF. However, mortality (HR1.43, 95% CI 1.18-1.75, P < .001) and risk of total cardiovascular events (HR 1.73, 95% CI 1.39-2.16, P < .001) were higher than age-, sex-, and cohort-matched individuals without AF.
Conclusions The risk of cardiovascular outcomes and mortality among individuals with AF without comorbidities is lower than typical AF, but is significantly elevated compared with matched individuals without AF.
C1 [Kim, Eun-Jeong] Massachusetts Gen Hosp, Dept Med, Gen Internal Med Sect, Boston, MA 02114 USA.
[Yin, Xiaoyan; Fontes, Joao D.; Magnani, Jared W.; Seshadri, Sudha; Vasan, Ramachandran S.; Larson, Martin G.; Benjamin, Emelia J.] NHLBI, Framingham, MA USA.
[Yin, Xiaoyan; Fontes, Joao D.; Magnani, Jared W.; Seshadri, Sudha; Vasan, Ramachandran S.; Larson, Martin G.; Benjamin, Emelia J.] Boston Univ Framingham Heart Study, Framingham, MA USA.
[Magnani, Jared W.; Vasan, Ramachandran S.; Benjamin, Emelia J.] Boston Univ, Sch Med, Dept Med, Sect Cardiovasc Med, Boston, MA 02215 USA.
[Lubitz, Steve A.; Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.
[Lubitz, Steve A.; Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA.
[Lubitz, Steve A.; Ellinor, Patrick T.] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA USA.
[McManus, David D.] Univ Massachusetts, Sch Med, Dept Med, Worcester, MA USA.
[McManus, David D.] Univ Massachusetts, Sch Med, Dept Quantitat Hlth Sci, Worcester, MA USA.
[Seshadri, Sudha] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA.
[Vasan, Ramachandran S.; Benjamin, Emelia J.] Boston Univ, Sch Med, Dept Med, Sect Prevent Med, Boston, MA 02118 USA.
[Larson, Martin G.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA.
[Larson, Martin G.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA.
[Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.
[Rienstra, Michiel] Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, NL-9700 RB Groningen, Netherlands.
RP Rienstra, M (reprint author), Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, NL-9700 RB Groningen, Netherlands.
EM m.rienstra@umcg.nl
OI Ramachandran, Vasan/0000-0001-7357-5970; Rienstra,
Michiel/0000-0002-2581-070X
FU Doris Duke Charitable Foundation [2014105]; NCATS NIH HHS [UL1
TR001453]; NCRR NIH HHS [KL2 RR031981]; NHLBI NIH HHS [N01 HC025195,
HHSN268201500001C, HHSN268201500001I, K23 HL114724, N01HC25195, R01
HL092577, R01 HL102214, R15 HL121761, RC1 HL101056]; NINDS NIH HHS [R01
NS017950]
NR 24
TC 1
Z9 1
U1 5
U2 10
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-8703
EI 1097-5330
J9 AM HEART J
JI Am. Heart J.
PD JUL
PY 2016
VL 177
BP 138
EP 144
DI 10.1016/j.ahj.2016.03.023
PG 7
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA DO0MN
UT WOS:000377473100018
PM 27297859
ER
PT J
AU Stolzenberg, S
Michino, M
LeVine, MV
Weinstein, H
Shi, L
AF Stolzenberg, Sebastian
Michino, Mayako
LeVine, Michael V.
Weinstein, Harel
Shi, Lei
TI Computational approaches to detect allosteric pathways in transmembrane
molecular machines
SO BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
LA English
DT Article
DE Molecular dynamics; Allosteric interaction network; Transmembrane
protein
ID PROTEIN-COUPLED RECEPTOR; GLUTAMATE TRANSPORTER HOMOLOG;
NEUROTRANSMITTER SODIUM SYMPORTERS; AMINO-ACID TRANSPORTERS;
CRYSTAL-STRUCTURE; NETWORK ANALYSIS; ION-BINDING; BIOMOLECULAR
SIMULATIONS; CONFORMATIONAL DYNAMICS; FUNCTIONAL SELECTIVITY
AB Many of the functions of transmembrane proteins involved in signal processing and transduction across the cell membrane are determined by allosteric couplings that propagate the functional effects well beyond the original site of activation. Data gathered from breakthroughs in biochemistry, crystallography, and single molecule fluorescence have established a rich basis of information for the study of molecular mechanisms in the allosteric couplings of such transmembrane proteins. The mechanistic details of these couplings, many of which have therapeutic implications, however, have only become accessible in synergy with molecular modeling and simulations. Here, we review some recent computational approaches that analyze allosteric coupling networks (ACNs) in transmembrane proteins, and in particular the recently developed Protein Interaction Analyzer (PIA) designed to study ACNs in the structural ensembles sampled by molecular dynamics simulations. The power of these computational approaches in interrogating the functional mechanisms of transmembrane proteins is illustrated with selected examples of recent experimental and computational studies pursued synergistically in the investigation of secondary active transporters and GPCRs. This article is part of a Special Issue entitled: Membrane Proteins edited by J.C. Gumbart and Sergei Noskov. Published by Elsevier B.V.
C1 [Stolzenberg, Sebastian] Computat Mol Biol Grp, Inst Math, Arnimallee 6, D-14195 Berlin, Germany.
[Stolzenberg, Sebastian; LeVine, Michael V.; Weinstein, Harel; Shi, Lei] Cornell Univ, Dept Physiol & Biophys, Weill Med Coll, New York, NY 10065 USA.
[Stolzenberg, Sebastian] Cornell Univ, Dept Phys, Ithaca, NY 14850 USA.
[Michino, Mayako; Shi, Lei] NIDA, Computat Chem & Mol Biophys Unit, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
[Weinstein, Harel] Cornell Univ, Inst Computat Biomed, Weill Med Coll, New York, NY 10065 USA.
RP Shi, L (reprint author), 333 Cassell Dr,Room 1121, Baltimore, MD 21224 USA.
EM lei.shi2@nih.gov
FU Intramural Research Program of the NIH, NIDA [ZIA DA000606-01];
DRS/Marie Curie Post-Doctoral POINT Fellowship [608829]; Ruth L.
Kirschstein National Research Service Award [F31DA035533]; NIH [P01
DA012408, U54 GM087519, R01 MH054137, R01 DA035263]; XSEDE (Stampede
supercomputer) [TG-MCB090132, TG-MCB120008]; Office of Science of the
U.S. Department of Energy [DE-AC05-00OR22725, DE-AC02-05CH11231];
[PSCA14026P]
FX This research was supported in part by Intramural Research Program of
the NIH, NIDA (LS and MM) (ZIA DA000606-01). SS is supported by a
DRS/Marie Curie Post-Doctoral POINT Fellowship (608829). MVL is
supported by Ruth L. Kirschstein National Research Service Award
F31DA035533. HW gratefully acknowledges support of research described
herein from NIH grants P01 DA012408, U54 GM087519, R01 MH054137, and R01
DA035263, and the computational resources used at XSEDE (Stampede
supercomputer, projects TG-MCB090132, TG-MCB120008); at the Oak Ridge
Leadership Computing Facility (ALCC allocation BIP109) supported by the
Office of Science of the U.S. Department of Energy under Contract No.
DE-AC05-00OR22725; an allocation at the National Energy Research
Scientific Computing Center (NERSC, repository m1710) supported by the
Office of Science of the U.S. Department of Energy under Contract No.
DE-AC02-05CH11231; an allocation on the Anton supercomputer (grant
number PSCA14026P); and the computational resources of the David A.
Cofrin Center for Biomedical Information in the HRH Prince Alwaleed Bin
Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine at
Weill Cornell Medical College.
NR 110
TC 7
Z9 7
U1 2
U2 10
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0005-2736
EI 0006-3002
J9 BBA-BIOMEMBRANES
JI Biochim. Biophys. Acta-Biomembr.
PD JUL
PY 2016
VL 1858
IS 7
SI SI
BP 1652
EP 1662
DI 10.1016/j.bbamem.2016.01.010
PN B
PG 11
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA DN7CP
UT WOS:000377233200010
PM 26806157
ER
PT J
AU Noskov, SY
Rostovtseva, TK
Chamberlin, AC
Teijido, O
Jiang, W
Bezrukov, SM
AF Noskov, Sergei Yu.
Rostovtseva, Tatiana K.
Chamberlin, Adam C.
Teijido, Oscar
Jiang, Wei
Bezrukov, Sergey M.
TI Current state of theoretical and experimental studies of the
voltage-dependent anion channel (VDAC)
SO BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
LA English
DT Article
DE VDAC; Molecular Dynamics simulations; Brownian Dynamics simulations;
Mitochondrial transport; Beta-barrel channel reconstitution; pH
regulation
ID FACILITATED MEMBRANE-TRANSPORT; MITOCHONDRIAL OUTER-MEMBRANE;
MOLECULAR-DYNAMICS METHOD; FREE-ENERGY CALCULATIONS; REPLICA EXCHANGE
METHOD; ISCHEMIA-REPERFUSION INJURY; PROTEIN-FOLDING SIMULATION;
HISTOGRAM ANALYSIS METHOD; BROWNIAN DYNAMICS; ION PERMEATION
AB Voltage-dependent anion channel (VDAC), the major channel of the mitochondrial outer membrane provides a controlled pathway for respiratory metabolites in and out of the mitochondria. In spite of the wealth of experimental data from structural, biochemical, and biophysical investigations, the exact mechanisms governing selective ion and metabolite transport, especially the role of titratable charged residues and interactions with soluble cytosolic proteins, remain hotly debated in the field. The computational advances hold a promise to provide a much sought-after solution to many of the scientific disputes around solute and ion transport through VDAC and hence, across the mitochondrial outer membrane. In this review, we examine how Molecular Dynamics, Free Energy, and Brownian Dynamics simulations of the large beta-barrel channel, VDAC, advanced our understanding. We will provide a short overview of non-conventional techniques and also discuss examples of how the modeling excursions into VDAC biophysics prospectively aid experimental efforts. This article is part of a Special Issue entitled: Membrane Proteins edited by J.C. Gumbart and Sergei Noskov. (C) 2016 Elsevier B.V. All rights reserved.
C1 [Noskov, Sergei Yu.] Univ Calgary, Dept Biol Sci, 2500 Univ Dr N-W, Calgary, AB T2N 1N4, Canada.
[Noskov, Sergei Yu.] Univ Calgary, Ctr Mol Simulat, 2500 Univ Dr N-W, Calgary, AB T2N 1N4, Canada.
[Rostovtseva, Tatiana K.; Teijido, Oscar; Bezrukov, Sergey M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Mol Transport, NIH, Bethesda, MD 20892 USA.
[Chamberlin, Adam C.] Ambry Genet, 15 Argonaut, Aliso Viejo, CA 92656 USA.
[Teijido, Oscar] Inst Med Sci & Genom Med, Dept Med Epigenet, EuroEspes Sta Marta de Babio S-N, Bergondo 15165, A Coruna, Spain.
[Jiang, Wei] Argonne Natl Lab, Leadership Comp Facil, 9700S Cass Ave, Lemont, IL 60439 USA.
RP Noskov, SY (reprint author), Univ Calgary, Dept Biol Sci, 2500 Univ Dr N-W, Calgary, AB T2N 1N4, Canada.; Noskov, SY (reprint author), Univ Calgary, Ctr Mol Simulat, 2500 Univ Dr N-W, Calgary, AB T2N 1N4, Canada.; Rostovtseva, TK; Bezrukov, SM (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Mol Transport, NIH, Bethesda, MD 20892 USA.
EM snoskov@ucalgary.ca; rostovtt@mail.nih.gov; bezrukos@mail.nih.gov
FU NICHD/NIH; National Sciences and Engineering Research Council
[RGPIN-315019]; Alberta Innovates Technical Futures Strategic Chair in
BioMolecular Simulations; Canadian Foundation for Innovation; Intramural
Research Program of the National Institutes of Health (NIH), Eunice
Kennedy Shriver National Institute of Child Health and Human Development
FX We would like to thank cordially Drs. Michael Grabe, Joshua Adelman and
Om Choudray for sharing their structural data on the VDAC-ATP
simulations. Drs. Wonpil Im, Benoit Roux and Pablo De Biase were
instrumental in implementing, developing and extending GCMC-BD
algorithms to a variety of systems providing excellent tools and advice
for modeling data shown in this submission. The work in S.Y.N. lab was
supported with intramural funding from NICHD/NIH and the National
Sciences and Engineering Research Council (discovery grant RGPIN-315019
to S.Y.N.). S.Y.N. was supported by the Alberta Innovates Technical
Futures Strategic Chair in BioMolecular Simulations. Computations were
performed on the West-Grid/Compute Canada facilities and the University
of Calgary TNK cluster supported by the Canadian Foundation for
Innovation. The simulations of ATP transport in VDAC channel with 2D
H-REMD were performed on MIRA Blue-Gene Cluster located in the Argonne
National Laboratory under Discretional Director's award. T.K.R. and
S.M.B. were supported by the Intramural Research Program of the National
Institutes of Health (NIH), Eunice Kennedy Shriver National Institute of
Child Health and Human Development.
NR 141
TC 4
Z9 4
U1 5
U2 12
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0005-2736
EI 0006-3002
J9 BBA-BIOMEMBRANES
JI Biochim. Biophys. Acta-Biomembr.
PD JUL
PY 2016
VL 1858
IS 7
SI SI
BP 1778
EP 1790
DI 10.1016/j.bbamem.2016.02.026
PN B
PG 13
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA DN7CP
UT WOS:000377233200021
PM 26940625
ER
PT J
AU Mukhija, K
Singhal, K
Angmo, S
Yadav, K
Yadav, H
Sandhir, R
Singhal, NK
AF Mukhija, Kimmi
Singhal, Kirti
Angmo, Stanzin
Yadav, Kamalendra
Yadav, Hariom
Sandhir, Rajat
Singhal, Nitin Kumar
TI Potential of Alginate Encapsulated Ferric Saccharate Microemulsions to
Ameliorate Iron Deficiency in Mice
SO BIOLOGICAL TRACE ELEMENT RESEARCH
LA English
DT Article
DE Microemulsions; Iron saccharate complex; Bioavailability;
Emulsification; Sodium alginate; Anemia
ID LIPID-PEROXIDATION; FERROUS SULFATE; ANTIOXIDANT STATUS;
BINDING-CAPACITY; OXIDATIVE STRESS; FREE-RADICALS; IN-VITRO;
MICROENCAPSULATION; SALTS; ANEMIA
AB Iron deficiency is one of the most prominent mineral deficiencies around the world, which especially affects large population of women and children. Development of new technologies to combat iron deficiency is on high demand. Therefore, we developed alginate microcapsule with encapsulated iron that had better oral iron bioavailability. Microcapsules containing iron with varying ratios of sodium alginate ferric(III)-saccharide were prepared using emulsification method. In vitro studies with Caco-2 cells suggested that newly synthesized microemulsions had better iron bioavailability as compared to commercially available iron dextran formulations. Ferrozine in vitro assay showed that alginate-encapsulated ferric galactose microemulsion (AFGM) had highest iron bioavailability in comparison to other four ferric saccharate microemulsions, namely AFGlM, AFMM, AFSM, and AFFM synthesized in our laboratory. Mice studies also suggested that AFGM showed higher iron absorption as indicated by increased serum iron, hemoglobin, and other hematopoietic measures with almost no toxicity at tested doses. Development of iron-loaded microemulsions leads to higher bioavailability of iron and can provide alternative strategies to treat iron deficiency.
C1 [Angmo, Stanzin; Yadav, Kamalendra; Yadav, Hariom; Singhal, Nitin Kumar] Natl Agri Food Biotechnol Inst, Mohali, Punjab, India.
[Mukhija, Kimmi; Singhal, Kirti; Sandhir, Rajat] Panjab Univ, Dept Biochem, Chandigarh 160014, Punjab, India.
[Yadav, Hariom] NIDDK, NIH, Bethesda, MD 20892 USA.
RP Singhal, NK (reprint author), Natl Agri Food Biotechnol Inst, Mohali, Punjab, India.
EM nitin@nabi.res.in
OI Yadav, Hariom/0000-0003-4504-1597
FU Department of Biotechnology; National Agri-Food Biotechnology Institute
FX Research was supported by the Department of Biotechnology and National
Agri-Food Biotechnology Institute grants.
NR 51
TC 0
Z9 0
U1 5
U2 9
PU HUMANA PRESS INC
PI TOTOWA
PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA
SN 0163-4984
EI 1559-0720
J9 BIOL TRACE ELEM RES
JI Biol. Trace Elem. Res.
PD JUL
PY 2016
VL 172
IS 1
BP 179
EP 192
DI 10.1007/s12011-015-0564-4
PG 14
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA DO0JT
UT WOS:000377465900020
PM 26637994
ER
PT J
AU Collins, PY
Kondos, L
Pillai, A
Joestl, SS
Frohlich, J
AF Collins, Pamela Y.
Kondos, Leeza
Pillai, Aravind
Joestl, Sarah S.
Frohlich, Janet
TI Passive Suicidal Ideation and Community Mental Health Resources in South
Africa
SO COMMUNITY MENTAL HEALTH JOURNAL
LA English
DT Article
DE Passive suicidal ideation; Community resources; Community mental health;
Africa; HIV/AIDS
ID AIDS-RELATED MORTALITY; SYSTEMATIC ANALYSIS; COPING STRATEGIES; GLOBAL
BURDEN; HIV; DEPRESSION; VALIDITY; QUESTIONNAIRE-9; BEHAVIOR; DISEASE
AB South African communities continue to experience elevated incidence and prevalence of HIV infection. Passive suicidal ideation (PSI) may be one expression of distress in high prevalence communities. We report the prevalence of PSI and examine the relationship between PSI and participation in community organizations in a semi-rural sample of South African adults (N = 594). The prevalence of PSI in the 2 weeks prior to the interview was 9.1 %. Members of burial societies (I (2) = 7.34; p = 0.01) and stokvels (I (2) = 4.1; p = 0.04) (community-based savings groups) reported significantly less PSI compared to other respondents. Using a multivariate model adjusted for demographic characteristics, psychological distress, and socioeconomic status, we found lower odds of reporting PSI for members of burial societies (OR 0.48, CI 0.25 -0.91). Participation in community organizations that provide contextually salient resources in settings with high levels of distress may be a resource for mental health.
C1 [Collins, Pamela Y.] NIMH, NIH, Bethesda, MD 20892 USA.
[Kondos, Leeza] US Agcy Int Dev, Inst Publ Hlth, Global Hlth Bur, Washington, DC 20523 USA.
[Pillai, Aravind] Columbia Univ, Mailman Sch Publ Hlth, New York, NY USA.
[Joestl, Sarah S.] CDC, Natl Ctr Hlth Stat, Hyattsville, MD USA.
[Frohlich, Janet] Univ KwaZulu Natal, Ctr AIDS Programme Res South Africa, Durban, South Africa.
RP Collins, PY (reprint author), NIMH, NIH, Bethesda, MD 20892 USA.
EM pamela.collins@nih.gov; lmkondos@gmail.com; ap2664@cumc.columbia.edu;
sjoestl@cdc.gov; Janet.Frohlich@caprisa.org
FU NIAID Center for AIDS Research [NIAID P30AI42848]
FX The majority of this work was conducted while Dr. Collins was at
Columbia University and supported by a pilot award through the NIAID
Center for AIDS Research grant (PI: Scott Hammer, NIAID P30AI42848). Dr.
Sarah Joestl contributed to this work while she was a doctoral candidate
at the Mailman School of Public Health at Columbia University. Ms. Leeza
Kondos contributed to this work while employed at the National Institute
of Mental Health. We gratefully acknowledge the contributions of Lise
Werner, Henri Carrara, Robert Sember, Beverly Haddad, Ezra Susser, Dana
March, Quarraisha Abdool-Karim and the CAPRISA research team. The views
expressed in this manuscript do not necessarily reflect those of the
National Institute of Mental Health or the US government.
NR 44
TC 0
Z9 0
U1 5
U2 5
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0010-3853
EI 1573-2789
J9 COMMUNITY MENT HLT J
JI Community Ment. Health J.
PD JUL
PY 2016
VL 52
IS 5
BP 541
EP 550
DI 10.1007/s10597-016-0003-9
PG 10
WC Health Policy & Services; Public, Environmental & Occupational Health;
Psychiatry
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health; Psychiatry
GA DN8ZJ
UT WOS:000377368300006
PM 27100867
ER
PT J
AU Schwartz, LH
Litiere, S
de Vries, E
Ford, R
Gwyther, S
Mandrekar, S
Shankar, L
Bogaerts, J
Chen, A
Dancey, J
Hayes, W
Hodi, FS
Hoekstra, OS
Huang, EP
Lin, N
Liu, Y
Therasse, P
Wolchok, JD
Seymour, L
AF Schwartz, Lawrence H.
Litiere, Saskia
de Vries, Elisabeth
Ford, Robert
Gwyther, Stephen
Mandrekar, Sumithra
Shankar, Lalitha
Bogaerts, Jan
Chen, Alice
Dancey, Janet
Hayes, Wendy
Hodi, F. Stephen
Hoekstra, Otto S.
Huang, Erich P.
Lin, Nancy
Liu, Yan
Therasse, Patrick
Wolchok, Jedd D.
Seymour, Lesley
TI RECIST 1.1-Update and clarification: From the RECIST committee
SO EUROPEAN JOURNAL OF CANCER
LA English
DT Article
DE RECIST; Clarifications; Tumour response
ID SOLID TUMORS
AB The Response Evaluation Criteria in Solid Tumours (RECIST) were developed and published in 2000, based on the original World Health Organisation guidelines first published in 1981. In 2009, revisions were made (RECIST 1.1) incorporating major changes, including a reduction in the number of lesions to be assessed, a new measurement method to classify lymph nodes as pathologic or normal, the clarification of the requirement to confirm a complete response or partial response and new methodologies for more appropriate measurement of disease progression. The purpose of this paper was to summarise the questions posed and the clarifications provided as an update to the 2009 publication. (C) 2016 Published by Elsevier Ltd.
C1 [Schwartz, Lawrence H.] Columbia Univ, Med Ctr, Dept Radiol, New York, NY USA.
[Schwartz, Lawrence H.] New York Presbyterian Hosp, New York, NY USA.
[Litiere, Saskia; Bogaerts, Jan; Liu, Yan] EORTC HQ, Brussels, Belgium.
[de Vries, Elisabeth] Univ Groningen, Univ Med Ctr Groningen, Dept Internal Med, NL-9713 AV Groningen, Netherlands.
[Ford, Robert] Clin Trials Imaging Consulting, Belle Mead, NJ USA.
[Gwyther, Stephen] East Surrey Hosp, Dept Med Imaging, Redhill, Surrey, England.
[Mandrekar, Sumithra] Mayo Clin, Div Biomed Stat & Informat, Rochester, MN USA.
[Shankar, Lalitha] NCI, Clin Trials Branch, Canc Imaging Program, Div Canc Treatment & Diag, Bethesda, MD 20892 USA.
[Chen, Alice] NCI, Early Clin Trials Dev Program, Div Canc Treatment & Diag, Bethesda, MD 20892 USA.
[Hayes, Wendy] Bristol Myers Squibb Co, Exploratory Clin & Translat Res, Princeton, NJ USA.
[Hodi, F. Stephen; Lin, Nancy] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA.
[Hoekstra, Otto S.] Vrije Univ Amsterdam, Med Ctr, Dept Radiol & Nucl Med, Amsterdam, Netherlands.
[Huang, Erich P.] NCI, NIH, Rockville, MD USA.
[Therasse, Patrick] Labs Servier, Paris, France.
[Wolchok, Jedd D.] Mem Sloan Kettering Canc Ctr, Dept Med, 1275 York Ave, New York, NY 10021 USA.
[Wolchok, Jedd D.] Weill Cornell Med Coll, New York, NY USA.
[Wolchok, Jedd D.] Grad Coll, New York, NY USA.
[Wolchok, Jedd D.] Ludwig Inst Canc Res, New York, NY USA.
[Dancey, Janet; Seymour, Lesley] Queens Univ, Canadian Canc Trials Grp, Kingston, ON, Canada.
RP Schwartz, LH (reprint author), CUMC, 180 Ft Washington Ave, New York, NY 10032 USA.
EM LSchwartz@columbia.edu
FU Canadian Cancer Society Research Institute [021039]; EORTC Cancer
Research Fund; National Cancer Institute (NCI) [5U10-CA11488-45]
FX Canadian Cancer Trials Group participation was supported by the Canadian
Cancer Society Research Institute (grant #021039). This publication was
supported by the EORTC Cancer Research Fund and by the National Cancer
Institute (NCI) grant number 5U10-CA11488-45.
NR 6
TC 2
Z9 2
U1 2
U2 4
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0959-8049
EI 1879-0852
J9 EUR J CANCER
JI Eur. J. Cancer
PD JUL
PY 2016
VL 62
BP 132
EP 137
DI 10.1016/j.ejca.2016.03.081
PG 6
WC Oncology
SC Oncology
GA DN9FO
UT WOS:000377385100015
PM 27189322
ER
PT J
AU Schwartz, LH
Seymour, L
Litiere, S
Ford, R
Gwyther, S
Mandrekar, S
Shankar, L
Bogaerts, J
Chen, A
Dancey, J
Hayes, W
Hodi, FS
Hoekstra, OS
Huang, EP
Lin, N
Liu, Y
Therasse, P
Wolchok, JD
de Vries, E
AF Schwartz, Lawrence H.
Seymour, Lesley
Litiere, Saskia
Ford, Robert
Gwyther, Stephen
Mandrekar, Sumithra
Shankar, Lalitha
Bogaerts, Jan
Chen, Alice
Dancey, Janet
Hayes, Wendy
Hodi, F. Stephen
Hoekstra, Otto S.
Huang, Erich P.
Lin, Nancy
Liu, Yan
Therasse, Patrick
Wolchok, Jedd D.
de Vries, Elisabeth
TI RECIST 1.1-Standardisation and disease-specific adaptations:
Perspectives from the RECIST Working Group
SO EUROPEAN JOURNAL OF CANCER
LA English
DT Article
DE RECIST; Modifications; Tumour response
ID METASTATIC PROSTATE-CANCER; RESPONSE ASSESSMENT CRITERIA; INTERNATIONAL
WORKSHOP; END-POINTS; LYMPHOMA; CHEMOTHERAPY; MANAGEMENT; CARCINOMA;
SURVIVAL; TRIALS
AB Radiologic imaging of disease sites plays a pivotal role in the management of patients with cancer. Response Evaluation Criteria in Solid Tumours (RECIST), introduced in 2000, and modified in 2009, has become the de facto standard for assessment of response in solid tumours in patients on clinical trials.
The RECIST Working Group considers the ability of the global oncology community to implement and adopt updates to RECIST in a timely manner to be critical. Updates to RECIST must be tested, validated and implemented in a standardised, methodical manner in response to therapeutic and imaging technology advances as well as experience gained by users. This was the case with the development of RECIST 1.1, where an expanded data warehouse was developed to test and validate modifications. Similar initiatives are ongoing, testing RECIST in the evaluation of response to non-cytotoxic agents, immunotherapies, as well as in specific diseases.
The RECIST Working Group has previously outlined the level of evidence considered necessary to formally and fully validate new imaging markers as an appropriate end-point for clinical trials. Achieving the optimal level of evidence desired is a difficult feat for phase III trials; this involves a meta -analysis of multiple prospective, randomised multicentre clinical trials. The rationale for modifications should also be considered; the modifications may be proposed to improve surrogacy, to provide a more mechanistic imaging technique, or be designed to improve reproducibility of the imaging biomarker.
Here, we present the commonly described modifications of RECIST, each of which is associated with different levels of evidence and validation. (C) 2016 Published by Elsevier Ltd.
C1 [Schwartz, Lawrence H.] Columbia Univ, Med Ctr, Dept Radiol, New York, NY USA.
[Schwartz, Lawrence H.] New York Presbyterian Hosp, New York, NY USA.
[Seymour, Lesley; Dancey, Janet] Queens Univ, Canadian Canc Trials Grp, Kingston, ON, Canada.
[Litiere, Saskia; Bogaerts, Jan; Liu, Yan] EORTC HQ, Brussels, Belgium.
[Ford, Robert] Clin Trials Imaging Consulting, Belle Mead, NJ USA.
[Gwyther, Stephen] East Surrey Hosp, Dept Med Imaging, Redhill, Surrey, England.
[Mandrekar, Sumithra] Mayo Clin, Div Biomed Stat & Informat, Rochester, MN USA.
[Shankar, Lalitha] NCI, Clin Trials Branch, Canc Imaging Program, Div Canc Treatment & Diag, Bethesda, MD 20892 USA.
[Chen, Alice] NCI, Early Clin Trials Dev Program, Div Canc Treatment & Diag, Bethesda, MD 20892 USA.
[Hayes, Wendy] Bristol Myers Squibb Co, Exploratory Clin & Translat Res, Princeton, NJ USA.
[Hodi, F. Stephen; Lin, Nancy] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA.
[Hoekstra, Otto S.] Vrije Univ Amsterdam, Med Ctr, Dept Radiol & Nucl Med, Amsterdam, Netherlands.
[Huang, Erich P.] NCI, NIH, Rockville, MD USA.
[Therasse, Patrick] Labs Servier, Paris, France.
[Wolchok, Jedd D.] Mem Sloan Kettering Canc Ctr, Dept Med, 1275 York Ave, New York, NY 10021 USA.
[Wolchok, Jedd D.] Weill Cornell Med Coll, New York, NY USA.
[Wolchok, Jedd D.] Grad Coll, New York, NY USA.
[Wolchok, Jedd D.] Ludwig Inst Canc Res, New York, NY USA.
[de Vries, Elisabeth] Univ Groningen, Univ Med Ctr Groningen, Dept Internal Med, NL-9713 AV Groningen, Netherlands.
RP Schwartz, LH (reprint author), Columbia Univ, Coll Phys & Surg, New York Presbyterian Hosp, Dept Radiol, 180 Ft Washington Ave, New York, NY 10032 USA.
EM LSchwartz@columbia.edu
FU Canadian Cancer Society Research Institute [021039]; EORTC Cancer
Research Fund; National Cancer Institute [5U10-CA11488-45]
FX Canadian Cancer Trials Group participation was supported by the Canadian
Cancer Society Research Institute (grant #021039). This publication was
supported by the EORTC Cancer Research Fund and by the National Cancer
Institute grant number 5U10-CA11488-45.
NR 22
TC 3
Z9 4
U1 0
U2 1
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0959-8049
EI 1879-0852
J9 EUR J CANCER
JI Eur. J. Cancer
PD JUL
PY 2016
VL 62
BP 138
EP 145
DI 10.1016/j.ejca.2016.03.082
PG 8
WC Oncology
SC Oncology
GA DN9FO
UT WOS:000377385100016
PM 27237360
ER
PT J
AU Cuellar-Partida, G
Lu, Y
Dixon, SC
Fasching, PA
Hein, A
Burghaus, S
Beckmann, MW
Lambrechts, D
Van Nieuwenhuysen, E
Vergote, I
Vanderstichele, A
Doherty, JA
Rossing, MA
Chang-Claude, J
Rudolph, A
Wang-Gohrke, S
Goodman, MT
Bogdanova, N
Dork, T
Durst, M
Hillemanns, P
Runnebaum, IB
Antonenkova, N
Butzow, R
Leminen, A
Nevanlinna, H
Pelttari, LM
Edwards, RP
Kelley, JL
Modugno, F
Moysich, KB
Ness, RB
Cannioto, R
Hogdall, E
Hogdall, C
Jensen, A
Giles, GG
Bruinsma, F
Kjaer, SK
Hildebrandt, MAT
Liang, D
Lu, KH
Wu, XF
Bisogna, M
Dao, F
Levine, DA
Cramer, DW
Terry, KL
Tworoger, SS
Stampfer, M
Missmer, S
Bjorge, L
Salvesen, HB
Kopperud, RK
Bischof, K
Aben, KKH
Kiemeney, LA
Massuger, LFAG
Brooks-Wilson, A
Olson, SH
McGuire, V
Rothstein, JH
Sieh, W
Whittemore, AS
Cook, LS
Le, ND
Gilks, CB
Gronwald, J
Jakubowska, A
Lubinski, J
Kluz, T
Song, HL
Tyrer, JP
Wentzensen, N
Brinton, L
Trabert, B
Lissowska, J
McLaughlin, JR
Narod, SA
Phelan, C
Anton-Culver, H
Ziogas, A
Eccles, D
Campbell, I
Gayther, SA
Gentry-Maharaj, A
Menon, U
Ramus, SJ
Wu, AH
Dansonka-Mieszkowska, A
Kupryjanczyk, J
Timorek, A
Szafron, L
Cunningham, JM
Fridley, BL
Winham, SJ
Bandera, EV
Poole, EM
Morgan, TK
Goode, EL
Schildkraut, JM
Pearce, CL
Berchuck, A
Pharoah, PDP
Webb, PM
Chenevix-Trench, G
Risch, HA
MacGregor, S
AF Cuellar-Partida, Gabriel
Lu, Yi
Dixon, Suzanne C.
Fasching, Peter A.
Hein, Alexander
Burghaus, Stefanie
Beckmann, Matthias W.
Lambrechts, Diether
Van Nieuwenhuysen, Els
Vergote, Ignace
Vanderstichele, Adriaan
Doherty, Jennifer Anne
Rossing, Mary Anne
Chang-Claude, Jenny
Rudolph, Anja
Wang-Gohrke, Shan
Goodman, Marc T.
Bogdanova, Natalia
Doerk, Thilo
Duerst, Matthias
Hillemanns, Peter
Runnebaum, Ingo B.
Antonenkova, Natalia
Butzow, Ralf
Leminen, Arto
Nevanlinna, Heli
Pelttari, Liisa M.
Edwards, Robert P.
Kelley, Joseph L.
Modugno, Francesmary
Moysich, Kirsten B.
Ness, Roberta B.
Cannioto, Rikki
Hogdall, Estrid
Hogdall, Claus
Jensen, Allan
Giles, Graham G.
Bruinsma, Fiona
Kjaer, Susanne K.
Hildebrandt, Michelle A. T.
Liang, Dong
Lu, Karen H.
Wu, Xifeng
Bisogna, Maria
Dao, Fanny
Levine, Douglas A.
Cramer, Daniel W.
Terry, Kathryn L.
Tworoger, Shelley S.
Stampfer, Meir
Missmer, Stacey
Bjorge, Line
Salvesen, Helga B.
Kopperud, Reidun K.
Bischof, Katharina
Aben, Katja K. H.
Kiemeney, Lambertus A.
Massuger, Leon F. A. G.
Brooks-Wilson, Angela
Olson, Sara H.
McGuire, Valerie
Rothstein, Joseph H.
Sieh, Weiva
Whittemore, Alice S.
Cook, Linda S.
Le, Nhu D.
Gilks, C. Blake
Gronwald, Jacek
Jakubowska, Anna
Lubinski, Jan
Kluz, Tomasz
Song, Honglin
Tyrer, Jonathan P.
Wentzensen, Nicolas
Brinton, Louise
Trabert, Britton
Lissowska, Jolanta
McLaughlin, John R.
Narod, Steven A.
Phelan, Catherine
Anton-Culver, Hoda
Ziogas, Argyrios
Eccles, Diana
Campbell, Ian
Gayther, Simon A.
Gentry-Maharaj, Aleksandra
Menon, Usha
Ramus, Susan J.
Wu, Anna H.
Dansonka-Mieszkowska, Agnieszka
Kupryjanczyk, Jolanta
Timorek, Agnieszka
Szafron, Lukasz
Cunningham, Julie M.
Fridley, Brooke L.
Winham, Stacey J.
Bandera, Elisa V.
Poole, Elizabeth M.
Morgan, Terry K.
Goode, Ellen L.
Schildkraut, Joellen M.
Pearce, Celeste L.
Berchuck, Andrew
Pharoah, Paul D. P.
Webb, Penelope M.
Chenevix-Trench, Georgia
Risch, Harvey A.
MacGregor, Stuart
CA Australian Ovarian Canc Study
TI Assessing the genetic architecture of epithelial ovarian cancer
histological subtypes
SO HUMAN GENETICS
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; MOLECULAR CHARACTERIZATION; SUSCEPTIBILITY
LOCUS; DIABETES-MELLITUS; PROVIDES INSIGHTS; HUMAN HEIGHT; COMMON SNPS;
RISK; METAANALYSIS; MUTATIONS
AB Epithelial ovarian cancer (EOC) is one of the deadliest common cancers. The five most common types of disease are high-grade and low-grade serous, endometrioid, mucinous and clear cell carcinoma. Each of these subtypes present distinct molecular pathogeneses and sensitivities to treatments. Recent studies show that certain genetic variants confer susceptibility to all subtypes while other variants are subtype-specific. Here, we perform an extensive analysis of the genetic architecture of EOC subtypes. To this end, we used data of 10,014 invasive EOC patients and 21,233 controls from the Ovarian Cancer Association Consortium genotyped in the iCOGS array (211,155 SNPs). We estimate the array heritability (attributable to variants tagged on arrays) of each subtype and their genetic correlations. We also look for genetic overlaps with factors such as obesity, smoking behaviors, diabetes, age at menarche and height. We estimated the array heritabilities of high-grade serous disease ( = 8.8 +/- 1.1 %), endometrioid ( = 3.2 +/- 1.6 %), clear cell ( = 6.7 +/- 3.3 %) and all EOC ( = 5.6 +/- 0.6 %). Known associated loci contributed approximately 40 % of the total array heritability for each subtype. The contribution of each chromosome to the total heritability was not proportional to chromosome size. Through bivariate and cross-trait LD score regression, we found evidence of shared genetic backgrounds between the three high-grade subtypes: serous, endometrioid and undifferentiated. Finally, we found significant genetic correlations of all EOC with diabetes and obesity using a polygenic prediction approach.
C1 [Cuellar-Partida, Gabriel; Lu, Yi; MacGregor, Stuart] Queensland Inst Med Res, Berghofer Med Res Inst, Stat Genet, 300 Herston Rd, Herston, Qld 4006, Australia.
[Cuellar-Partida, Gabriel] Univ Queensland, Sch Med, St Lucia, Qld 4072, Australia.
[Dixon, Suzanne C.; Webb, Penelope M.] Queensland Inst Med Res, Berghofer Med Res Inst, Gynaecol Canc Grp, 300 Herston Rd, Herston, Qld 4006, Australia.
[Chenevix-Trench, Georgia] Queensland Inst Med Res, Berghofer Med Res Inst, Canc Genet, 300 Herston Rd, Herston, Qld 4006, Australia.
[Campbell, Ian; Australian Ovarian Canc Study] Peter MacCallum Canc Ctr, Div Res, St Andrews Pl, East Melbourne, Vic, Australia.
[Pharoah, Paul D. P.] Univ Cambridge, Ctr Canc Genet Epidemiol, Dept Publ Hlth & Primary Care, Cambridge, England.
[Fasching, Peter A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Hematol & Oncol, Los Angeles, CA 90095 USA.
[Fasching, Peter A.; Hein, Alexander; Burghaus, Stefanie; Beckmann, Matthias W.] Univ Erlangen Nurnberg, Univ Hosp Erlangen, Dept Gynecol & Obstet, Comprehens Canc Ctr Erlangen EMN, Univ Str 21-23, D-91054 Erlangen, Germany.
[Lambrechts, Diether] Univ Leuven, Dept Oncol, Lab Translat Genet, Leuven, Belgium.
[Lambrechts, Diether] VIB, Vesalius Res Ctr, Louvain, Belgium.
[Van Nieuwenhuysen, Els; Vanderstichele, Adriaan] Univ Hosp Leuven, Dept Obstet & Gynaecol, Div Gynecol Oncol, Louvain, Belgium.
[Van Nieuwenhuysen, Els; Vergote, Ignace; Vanderstichele, Adriaan] Univ Hosp Leuven, Leuven Canc Inst, Louvain, Belgium.
[Doherty, Jennifer Anne] Dartmouth Coll, Geisel Sch Med, Dept Community & Family Med, Epidemiol & Biostat Sect, Hanover, NH 03755 USA.
[Rossing, Mary Anne] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
[Rossing, Mary Anne] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Program Epidemiol, 1124 Columbia St, Seattle, WA 98104 USA.
[Chang-Claude, Jenny; Rudolph, Anja] German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany.
[Wang-Gohrke, Shan] Univ Ulm, Dept Obstet & Gynecol, D-89069 Ulm, Germany.
[Goodman, Marc T.] Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Inst, Canc Prevent & Control, Los Angeles, CA 90048 USA.
[Goodman, Marc T.] Cedars Sinai Med Ctr, Community & Populat Hlth Res Inst, Dept Biomed Sci, Los Angeles, CA 90048 USA.
[Bogdanova, Natalia] Hannover Med Sch, Radiat Oncol Res Unit, Hannover, Germany.
[Doerk, Thilo] Hannover Med Sch, Gynaecol Res Unit, Hannover, Germany.
[Duerst, Matthias; Runnebaum, Ingo B.] Univ Jena, Hospital Friedrich Schiller Univ, Dept Gynecol, Jena, Germany.
[Hillemanns, Peter] Hannover Med Sch, Clin Obstet, Hannover, Germany.
[Hillemanns, Peter] Hannover Med Sch, Clin Gynaecol, Hannover, Germany.
[Antonenkova, Natalia] NN Alexandrov Natl Canc Ctr Belarus, Minsk, Byelarus.
[Butzow, Ralf] Univ Helsinki, Dept Pathol, Helsinki, Finland.
[Butzow, Ralf; Leminen, Arto; Nevanlinna, Heli; Pelttari, Liisa M.] Helsinki Univ Hosp, Helsinki, Finland.
[Leminen, Arto; Nevanlinna, Heli; Pelttari, Liisa M.] Univ Helsinki, Dept Obstet & Gynecol, Helsinki, Finland.
[Edwards, Robert P.; Kelley, Joseph L.; Modugno, Francesmary] Univ Pittsburgh, Sch Med, Div Gynecol Oncol, Dept Obstet Gynecol & Reprod Sci, Pittsburgh, PA USA.
[Edwards, Robert P.; Modugno, Francesmary] Magee Womens Res Inst, Womens Canc Res Program, Pittsburgh, PA USA.
[Edwards, Robert P.; Modugno, Francesmary] Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA.
[Modugno, Francesmary] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA.
[Moysich, Kirsten B.; Cannioto, Rikki] Roswell Pk Canc Inst, Dept Canc Prevent & Control, Buffalo, NY 14263 USA.
[Ness, Roberta B.] Univ Texas Houston, Sch Publ Hlth, Houston, TX USA.
[Hogdall, Estrid; Jensen, Allan; Kjaer, Susanne K.] Danish Canc Soc Res Ctr, Dept Virus Lifestyle & Genes, Copenhagen, Denmark.
[Hogdall, Estrid] Univ Copenhagen, Herlev Hosp, Dept Pathol, Mol Unit, Copenhagen, Denmark.
[Giles, Graham G.] Monash Univ, Dept Epidemiol & Prevent Med, Melbourne, Vic 3004, Australia.
[Giles, Graham G.] Univ Melbourne, Melbourne Sch Populat & Global Hlth, Ctr Biostat & Epidemiol, Melbourne, Vic, Australia.
[Giles, Graham G.; Bruinsma, Fiona] Canc Council Victoria, Canc Epidemiol Ctr, Melbourne, Vic, Australia.
[Hogdall, Claus; Kjaer, Susanne K.] Univ Copenhagen, Rigshosp, Dept Gynaecol, DK-2100 Copenhagen, Denmark.
[Hildebrandt, Michelle A. T.; Wu, Xifeng] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA.
[Liang, Dong] Texas So Univ, Coll Pharm & Hlth Sci, Houston, TX 77004 USA.
[Lu, Karen H.] Univ Texas MD Anderson Canc Ctr, Dept Gynecol Oncol, Houston, TX 77030 USA.
[Bisogna, Maria; Dao, Fanny; Levine, Douglas A.] Mem Sloan Kettering Canc Ctr, Dept Surg, Gynecol Serv, New York, NY 10021 USA.
[Cramer, Daniel W.; Terry, Kathryn L.; Missmer, Stacey] Brigham & Womens Hosp, Obstet & Gynecol Epidemiol Ctr, 75 Francis St, Boston, MA 02115 USA.
[Terry, Kathryn L.; Tworoger, Shelley S.; Stampfer, Meir; Missmer, Stacey] Harvard Univ, TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Tworoger, Shelley S.; Stampfer, Meir; Missmer, Stacey; Poole, Elizabeth M.] Brigham & Womens Hosp, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA.
[Tworoger, Shelley S.; Stampfer, Meir; Missmer, Stacey; Poole, Elizabeth M.] Harvard Univ, Sch Med, Boston, MA USA.
[Dixon, Suzanne C.; Webb, Penelope M.] Univ Queensland, Sch Publ Hlth, Herston, Qld 4006, Australia.
[Bjorge, Line; Salvesen, Helga B.; Kopperud, Reidun K.; Bischof, Katharina] Haukeland Hosp, Dept Gynecol & Obstet, N-5021 Bergen, Norway.
[Bjorge, Line; Salvesen, Helga B.; Kopperud, Reidun K.; Bischof, Katharina] Univ Bergen, Ctr Canc Biomarkers, Dept Clin Sci, Bergen, Norway.
[Aben, Katja K. H.; Kiemeney, Lambertus A.] Radboud Univ Nijmegen, Med Ctr, RADBOUD Inst Hlth Sci, NL-6525 ED Nijmegen, Netherlands.
[Aben, Katja K. H.] Netherlands Comprehens Canc Org, Utrecht, Netherlands.
[Massuger, Leon F. A. G.] Radboud Univ Nijmegen, Med Ctr, Radboud Inst Mol Life Sci, Dept Obstet & Gynaecol, NL-6525 ED Nijmegen, Netherlands.
[Brooks-Wilson, Angela] BC Canc Agcy, Canadas Michael Smith Genome Sci Ctr, Vancouver, BC, Canada.
[Brooks-Wilson, Angela] Simon Fraser Univ, Dept Biomed Physiol & Kinesiol, Burnaby, BC V5A 1S6, Canada.
[Olson, Sara H.] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA.
[McGuire, Valerie; Rothstein, Joseph H.; Sieh, Weiva; Whittemore, Alice S.] Stanford Univ, Sch Med, Dept Hlth Res & Policy Epidemiol, Stanford, CA 94305 USA.
[Cook, Linda S.] Univ New Mexico, Dept Internal Med, Div Epidemiol & Biostat, Albuquerque, NM 87131 USA.
[Le, Nhu D.] BC Canc Agcy, Canc Control Res, Vancouver, BC, Canada.
[Gilks, C. Blake] Univ British Columbia, Pathol & Lab Med, Vancouver, BC V5Z 1M9, Canada.
[Gronwald, Jacek; Jakubowska, Anna; Lubinski, Jan] Pomeranian Med Univ, Int Hereditary Canc Ctr, Dept Genet & Pathol, Szczecin, Poland.
[Kluz, Tomasz] Univ Rzeszow, Frederick Chopin Clin Prov Hosp 1, Clin Obstet & Gynecol, Fac Med,Inst Midwifery & Emergency Med, Rzeszow, Poland.
[Song, Honglin; Tyrer, Jonathan P.; Pharoah, Paul D. P.] Univ Cambridge, Ctr Canc Genet Epidemiol, Dept Oncol, Cambridge, England.
[Wentzensen, Nicolas; Brinton, Louise; Trabert, Britton] Natl Canc Inst, Div Canc Epidemiol & Genet, Bethesda, MD USA.
[Lissowska, Jolanta] Maria Sklodowska Curie Mem Canc Ctr, Dept Canc Epidemiol & Prevent, Warsaw, Poland.
[Lissowska, Jolanta] Inst Oncol, Warsaw, Poland.
[McLaughlin, John R.] Publ Hlth Ontario, Toronto, ON, Canada.
[Narod, Steven A.] Univ Toronto, Womens Coll Res Inst, Toronto, ON, Canada.
[Phelan, Catherine] H Lee Moffitt Canc Ctr & Res Inst, Dept Canc Epidemiol, Tampa, FL USA.
[Anton-Culver, Hoda; Ziogas, Argyrios] Univ Calif Irvine, Dept Epidemiol, Irvine, CA USA.
[Anton-Culver, Hoda] Univ Calif Irvine, Sch Med, Ctr Canc Genet Res & Prevent, Irvine, CA USA.
[Eccles, Diana] Univ Southampton, Fac Med, Southampton SO9 5NH, Hants, England.
[Gayther, Simon A.; Ramus, Susan J.; Wu, Anna H.; Pearce, Celeste L.] Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA.
[Gentry-Maharaj, Aleksandra] UCL, Inst Womens Hlth, Womens Canc, London, England.
[Dansonka-Mieszkowska, Agnieszka; Kupryjanczyk, Jolanta; Szafron, Lukasz] Maria Sklodowska Curie Mem Canc Ctr, Dept Pathol & Lab Diagnost, Warsaw, Poland.
[Dansonka-Mieszkowska, Agnieszka; Kupryjanczyk, Jolanta; Szafron, Lukasz] Inst Oncol, Warsaw, Poland.
[Timorek, Agnieszka] Med Univ Warsaw, Fac Med 2, Dept Obstet Gynaecol & Oncol, Warsaw, Poland.
[Timorek, Agnieszka] Brodnowski Hosp, Warsaw, Poland.
[Cunningham, Julie M.] Mayo Clin, Dept Lab Med & Pathol, Div Expt Pathol, Rochester, MN USA.
[Fridley, Brooke L.] Univ Kansas, Dept Biostat, Kansas City, KS USA.
[Winham, Stacey J.] Mayo Clin, Dept Hlth Sci Res, Div Biomed Stat & Informat, Rochester, MN USA.
[Bandera, Elisa V.] Rutgers Canc Inst New Jersey, New Brunswick, NJ USA.
[Morgan, Terry K.] OHSU, Dept Pathol & Obstet, Portland, OR USA.
[Morgan, Terry K.] OHSU, Dept Gynaecol, Portland, OR USA.
[Goode, Ellen L.] Mayo Clin, Dept Hlth Sci Res, Div Epidemiol, Rochester, MN USA.
[Schildkraut, Joellen M.] Univ Virginia, Dept Publ Hlth Sci, Charlottesville, VA 22903 USA.
[Pearce, Celeste L.] Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA.
[Berchuck, Andrew] Duke Univ, Med Ctr, Duke Canc Inst, Durham, NC USA.
RP Cuellar-Partida, G; MacGregor, S (reprint author), Queensland Inst Med Res, Berghofer Med Res Inst, Stat Genet, 300 Herston Rd, Herston, Qld 4006, Australia.; Cuellar-Partida, G (reprint author), Univ Queensland, Sch Med, St Lucia, Qld 4072, Australia.
EM gabriel.cuellar@qimrberghofer.edu.au;
Stuart.MacGregor@qimrberghofer.edu.au
RI Trabert, Britton/F-8051-2015; Hein, Alexander/F-6999-2010; Dork,
Thilo/J-8620-2012; Gronwald, Jacek/A-4576-2017; Bjorge,
Line/C-1307-2017; salvesen, Helga/C-1187-2017; Cuellar Partida,
Gabriel/C-6686-2017; Brooks-Wilson, Angela/E-9399-2012;
OI Hein, Alexander/0000-0003-2601-3398; Gronwald,
Jacek/0000-0002-3643-2871; Bjorge, Line/0000-0002-0240-2770; salvesen,
Helga/0000-0002-4438-8831; Cuellar Partida, Gabriel/0000-0001-7648-4097;
Brooks-Wilson, Angela/0000-0003-1009-6408; Ramus,
Susan/0000-0003-0005-7798; Winham, Stacey/0000-0002-8492-9102
FU Ovarian Cancer Research Fund; California Cancer Research Program
[00-01389V-20170, N01-CN25403, 2II0200]; Canadian Institutes of Health
Research [MOP-86727]; Cancer Australia; Cancer Council Victoria; Cancer
Council Queensland; Cancer Council New South Wales; Cancer Council South
Australia; Cancer Council Tasmania; Cancer Foundation of Western
Australia; Cancer Institute of New Jersey; Cancer Research UK
[C490/A6187, C490/A10119, C490/A10124]; Danish Cancer Society
[94-222-52]; ELAN Program of the University of Erlangen-Nuremberg; Eve
Appeal; Helsinki University Central Hospital Research Fund; Helse Vest;
Norwegian Cancer Society; Norwegian Research Council; National
Kankerplan of Belgium; L & S Milken Foundation; Polish Ministry of
Science and Higher Education [4 PO5C 028 14, 2 PO5A 068 27]; Roswell
Park Cancer Institute Alliance Foundation; US National Cancer Institute
[K07-CA095666, K07-CA80668, K07-CA143047, K22-CA138563, N01-CN55424,
N01-PC67001, N01-PC067010, N01-PC035137, P01-CA017054, P01-CA087696,
P30-CA072720, P30-CA15083, P30-CA008748, P50-CA159981, P50-CA105009,
P50-CA136393, U01-CA069417, U01-CA071966]; NIH/National Center for
Research Resources/General Clinical Research Center [MO1-RR000056]; US
Army Medical Research and Material Command [DAMD17-01-1-0729,
DAMD17-02-1-0666, DAMD17-02-1-0669, W81XWH-07-0449, W81XWH-10-1-02802];
US Public Health Service [PSA-042205]; National Health and Medical
Research Council of Australia [199600, 400281]; German Federal Ministry
of Education and Research of Germany Programme of Clinical Biomedical
Research [01 GB 9401]; State of Baden-Wurttemberg through Medical
Faculty of the University of Ulm [P.685]; German Cancer Research Center;
Minnesota Ovarian Cancer Alliance; Mayo Foundation; Fred C. and
Katherine B. Andersen Foundation; Lon V. Smith Foundation [LVS-39420];
Oak Foundation; OHSU Foundation; Mermaid I project; Rudolf-Bartling
Foundation; UK National Institute for Health Research Biomedical
Research Centres at the University of Cambridge; Imperial College
London; University College Hospital 'Womens Health Theme'; Royal Marsden
Hospital; WorkSafeBC [14]; University of Queensland; QIMR Berghofer;
NHMRC Early Career Fellowship; National Health and Medical Research
Council; ARC Future Fellowship; The US National Cancer Institute
[R01-CA058860, R01-CA061107, R01-CA061132, R01-CA063678, R01-CA063682,
R01-CA067262, R01-CA071766, R01-CA074850, R01-CA080978, R01-CA083918,
R01-CA087538, R01-CA092044, R01-CA095023, R01-CA122443, R01-CA112523,
R01-CA149429, R01-CA014089, R01-CA016056]; A US National Cancer
Institute [UM1-CA186107, UM1-CA176726, R01-CA050385, R01-CA054419,
R01-CA058598, R01-CA114343, R01-CA126841, R01-CA136924, R03-CA113148,
R03-CA115195, R01-CA017054, R01-CA049449]
FX The Ovarian Cancer Association Consortium is supported by a grant from
the Ovarian Cancer Research Fund, thanks to donations by the family and
friends of Kathryn Sladek Smith (PPD/RPCI.07). The Nurses' Health
Studies would like to thank the participants and staff of the Nurses'
Health Study and Nurses' Health Study II for their valuable
contributions as well as the following state cancer registries for their
help: AL, AZ, AR, CA, CO, CT, DE, FL, GA, ID, IL, IN, IA, KY, LA, ME,
MD, MA, MI, NE, NH, NJ, NY, NC, ND, OH, OK, OR, PA, RI, SC, TN, TX, VA,
WA, WY. The authors assume full responsibility for analyses and
interpretation of these data. Funding of the constituent studies was
provided by the California Cancer Research Program (00-01389V-20170,
N01-CN25403, 2II0200); the Canadian Institutes of Health Research
(MOP-86727); Cancer Australia; Cancer Council Victoria; Cancer Council
Queensland; Cancer Council New South Wales; Cancer Council South
Australia; Cancer Council Tasmania; Cancer Foundation of Western
Australia; the Cancer Institute of New Jersey; Cancer Research UK
(C490/A6187, C490/A10119, C490/A10124); the Danish Cancer Society
(94-222-52); the ELAN Program of the University of Erlangen-Nuremberg;
the Eve Appeal; the Helsinki University Central Hospital Research Fund;
Helse Vest; the Norwegian Cancer Society; the Norwegian Research
Council; the Ovarian Cancer Research Fund; National Kankerplan of
Belgium; the L & S Milken Foundation; the Polish Ministry of Science and
Higher Education (4 PO5C 028 14, 2 PO5A 068 27); the Roswell Park Cancer
Institute Alliance Foundation; the US National Cancer Institute
(K07-CA095666, K07-CA80668, K07-CA143047, K22-CA138563, N01-CN55424,
N01-PC67001, N01-PC067010, N01-PC035137, P01-CA017054, P01-CA087696,
P30-CA072720, P30-CA15083, P30-CA008748, P50-CA159981, P50-CA105009,
P50-CA136393, R01-CA149429, R01-CA014089, R01-CA016056, R01-CA017054,
R01-CA049449, R01-CA050385, R01-CA054419, R01-CA058598, R01-CA058860,
R01-CA061107, R01-CA061132, R01-CA063678, R01-CA063682, R01-CA067262,
R01-CA071766, R01-CA074850, R01-CA080978, R01-CA083918, R01-CA087538,
R01-CA092044, R01-CA095023, R01-CA122443, R01-CA112523, R01-CA114343,
R01-CA126841, R01-CA136924, R03-CA113148, R03-CA115195, U01-CA069417,
U01-CA071966, UM1-CA186107, UM1-CA176726 and Intramural research funds);
the NIH/National Center for Research Resources/General Clinical Research
Center (MO1-RR000056); the US Army Medical Research and Material Command
(DAMD17-01-1-0729, DAMD17-02-1-0666, DAMD17-02-1-0669, W81XWH-07-0449,
W81XWH-10-1-02802); the US Public Health Service (PSA-042205); the
National Health and Medical Research Council of Australia (199600 and
400281); the German Federal Ministry of Education and Research of
Germany Programme of Clinical Biomedical Research (01 GB 9401); the
State of Baden-Wurttemberg through Medical Faculty of the University of
Ulm (P.685); the German Cancer Research Center; the Minnesota Ovarian
Cancer Alliance; the Mayo Foundation; the Fred C. and Katherine B.
Andersen Foundation; the Lon V. Smith Foundation (LVS-39420); the Oak
Foundation; Eve Appeal; the OHSU Foundation; the Mermaid I project; the
Rudolf-Bartling Foundation; the UK National Institute for Health
Research Biomedical Research Centres at the University of Cambridge,
Imperial College London, University College Hospital 'Womens Health
Theme' and the Royal Marsden Hospital; and WorkSafeBC 14.
Investigator-specific funding: G.C.P receives scholarship support from
the University of Queensland and QIMR Berghofer. Y. L.; was supported by
the NHMRC Early Career Fellowship. G. C. T. is supported by the National
Health and Medical Research Council. S. M. was supported by an ARC
Future Fellowship.
NR 60
TC 0
Z9 0
U1 4
U2 15
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0340-6717
EI 1432-1203
J9 HUM GENET
JI Hum. Genet.
PD JUL
PY 2016
VL 135
IS 7
BP 741
EP 756
DI 10.1007/s00439-016-1663-9
PG 16
WC Genetics & Heredity
SC Genetics & Heredity
GA DN8XX
UT WOS:000377364300007
PM 27075448
ER
PT J
AU Benedict, SH
Hoffman, K
Martel, MK
Abernethy, AP
Asher, AL
Capala, J
Chen, RC
Chera, B
Couch, J
Deye, J
Efstathiou, JA
Ford, E
Fraass, BA
Gabriel, PE
Huser, V
Kavanagh, BD
Khuntia, D
Marks, LB
Mayo, C
McNutt, T
Miller, RS
Moore, KL
Prior, F
Roelofs, E
Rosenstein, BS
Sloan, J
Theriault, A
Vikram, B
AF Benedict, Stanley H.
Hoffman, Karen
Martel, Mary K.
Abernethy, Amy P.
Asher, Anthony L.
Capala, Jacek
Chen, Ronald C.
Chera, Bhisham
Couch, Jennifer
Deye, James
Efstathiou, Jason A.
Ford, Eric
Fraass, Benedick A.
Gabriel, Peter E.
Huser, Vojtech
Kavanagh, Brian D.
Khuntia, Deepak
Marks, Lawrence B.
Mayo, Charles
McNutt, Todd
Miller, Robert S.
Moore, Kevin L.
Prior, Fred
Roelofs, Erik
Rosenstein, Barry S.
Sloan, Jeff
Theriault, Anna
Vikram, Bhadrasain
TI Overview of the American Society for Radiation Oncology-National
Institutes of Health-American Association of Physicists in Medicine
Workshop 2015: Exploring Opportunities for Radiation Oncology in the Era
of Big Data
SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
LA English
DT Editorial Material
ID SECONDARY USE; RADIOTHERAPY; FRAMEWORK; CARE
C1 [Benedict, Stanley H.] Univ Calif Davis, Sacramento, CA 95817 USA.
[Hoffman, Karen; Martel, Mary K.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Benedict, Stanley H.] Univ Calif Davis, Sacramento, CA 95817 USA.
[Hoffman, Karen; Martel, Mary K.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Abernethy, Amy P.] Duke Univ, Durham, NC USA.
[Asher, Anthony L.] Amer Assoc Neurol Surg, Rolling Meadows, IL USA.
[Capala, Jacek] NCI, Clin Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA.
[Chen, Ronald C.; Chera, Bhisham; Marks, Lawrence B.] Univ N Carolina, Sch Med, Chapel Hill, NC USA.
[Couch, Jennifer; Deye, James; Vikram, Bhadrasain] NCI, NIH, Bethesda, MD 20892 USA.
[Efstathiou, Jason A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA.
[Ford, Eric] Univ Washington, Seattle, WA 98195 USA.
[Fraass, Benedick A.] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA.
[Gabriel, Peter E.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Huser, Vojtech] Natl Lib Med, Lister Hill Natl Ctr Biomed Commun, NIH, Bethesda, MD USA.
[Kavanagh, Brian D.] Univ Colorado, Denver, CO 80202 USA.
[Khuntia, Deepak] Varian Med Syst, Palo Alto, CA USA.
[Mayo, Charles] Univ Michigan, Ann Arbor, MI 48109 USA.
[McNutt, Todd] Johns Hopkins Univ, Sch Med, Baltimore, MD USA.
[Miller, Robert S.] Amer Soc Clin Oncol, Alexandria, VA USA.
[Moore, Kevin L.] Univ Calif San Diego, La Jolla, CA 92093 USA.
[Prior, Fred] Univ Arkansas Med Sci, Little Rock, AR 72205 USA.
[Roelofs, Erik] Maastricht Univ, Med Ctr, Dept Radiat Oncol MAASTRO, GROW Sch Oncol & Dev Biol, NL-6200 MD Maastricht, Netherlands.
[Rosenstein, Barry S.] Icahn Sch Med Mt Sinai, New York, NY 10029 USA.
[Sloan, Jeff] Mayo Clin, Rochester, MN USA.
[Theriault, Anna] Elekta, Sunnyvale, CA USA.
RP Benedict, SH (reprint author), Univ Calif Davis, Sacramento, CA 95817 USA.
EM shbenedict@ucdavis.edu
FU NCI NIH HHS [U01 CA187013]
NR 18
TC 1
Z9 1
U1 2
U2 5
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0360-3016
EI 1879-355X
J9 INT J RADIAT ONCOL
JI Int. J. Radiat. Oncol. Biol. Phys.
PD JUL 1
PY 2016
VL 95
IS 3
BP 873
EP 879
DI 10.1016/j.ijrobp.2016.03.006
PG 7
WC Oncology; Radiology, Nuclear Medicine & Medical Imaging
SC Oncology; Radiology, Nuclear Medicine & Medical Imaging
GA DN9AE
UT WOS:000377370600003
PM 27302503
ER
PT J
AU Huser, V
Cimino, JJ
AF Huser, Vojtech
Cimino, James J.
TI Impending Challenges for the Use of Big Data
SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
LA English
DT Editorial Material
ID ONCOLOGY; RISK
C1 [Huser, Vojtech] NIH, Lister Hill Natl Ctr Biomed Commun, Natl Lib Med, 8600 Rockville Pike,Bld 38a,Rm 9N919, Bethesda, MD 20894 USA.
[Cimino, James J.] Univ Alabama Birmingham, Inst Informat, Birmingham, AL USA.
RP Huser, V (reprint author), NIH, Lister Hill Natl Ctr Biomed Commun, Natl Lib Med, 8600 Rockville Pike,Bld 38a,Rm 9N919, Bethesda, MD 20894 USA.
EM vojtech.huser@nih.gov
FU Intramural NIH HHS [ZIH CL000907-02, Z99 LM999999]
NR 16
TC 1
Z9 1
U1 3
U2 7
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0360-3016
EI 1879-355X
J9 INT J RADIAT ONCOL
JI Int. J. Radiat. Oncol. Biol. Phys.
PD JUL 1
PY 2016
VL 95
IS 3
BP 890
EP 894
DI 10.1016/j.ijrobp.2015.10.060
PG 5
WC Oncology; Radiology, Nuclear Medicine & Medical Imaging
SC Oncology; Radiology, Nuclear Medicine & Medical Imaging
GA DN9AE
UT WOS:000377370600006
PM 26797535
ER
PT J
AU Rosenstein, BS
Capala, J
Efstathiou, JA
Hammerbacher, J
Kerns, SL
Kong, FM
Ostrer, H
Prior, FW
Vikram, B
Wong, J
Xiao, Y
AF Rosenstein, Barry S.
Capala, Jacek
Efstathiou, Jason A.
Hammerbacher, Jeff
Kerns, Sarah L.
Kong, Feng-Ming (Spring)
Ostrer, Harry
Prior, Fred W.
Vikram, Bhadrasain
Wong, John
Xiao, Ying
TI How Will Big Data Improve Clinical and Basic Research in Radiation
Therapy?
SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
LA English
DT Editorial Material
ID GENOME-WIDE ASSOCIATION; CANCER IMAGING ARCHIVE; SINGLE-NUCLEOTIDE
POLYMORPHISMS; RADIOTHERAPY TOXICITY; PROSTATE-CANCER; RADIOGENOMICS;
MEDICINE; NETWORK; HEALTH; ONCOLOGY
C1 [Rosenstein, Barry S.] Icahn Sch Med Mt Sinai, Dept Radiat Oncol, One Gustave L Levy Pl,Box 1236, New York, NY 10029 USA.
[Rosenstein, Barry S.; Hammerbacher, Jeff] Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, New York, NY 10029 USA.
[Rosenstein, Barry S.] Icahn Sch Med Mt Sinai, Dept Dermatol, New York, NY 10029 USA.
[Rosenstein, Barry S.] Icahn Sch Med Mt Sinai, Dept Prevent Med, New York, NY 10029 USA.
[Rosenstein, Barry S.] NYU, Sch Med, Dept Radiat Oncol, New York, NY USA.
[Capala, Jacek; Vikram, Bhadrasain] NCI, Clin Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA.
[Efstathiou, Jason A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA USA.
[Kerns, Sarah L.] Univ Rochester, Med Ctr, Dept Radiat Oncol, Rochester, NY 14642 USA.
[Kong, Feng-Ming (Spring)] Georgia Regents Univ, GRU Canc Ctr, Dept Radiat Oncol, Augusta, GA USA.
[Kong, Feng-Ming (Spring)] Georgia Regents Univ, Med Coll Georgia, Augusta, GA USA.
[Ostrer, Harry] Albert Einstein Coll Med, Dept Pathol, Bronx, NY 10467 USA.
[Ostrer, Harry] Albert Einstein Coll Med, Dept Pediat, Bronx, NY 10467 USA.
[Prior, Fred W.] Univ Arkansas Med Sci, Dept Biomed Informat, Little Rock, AR 72205 USA.
[Wong, John] Johns Hopkins Univ, Sch Med, Dept Radiat Oncol, Baltimore, MD USA.
[Xiao, Ying] Univ Penn, Dept Radiat Oncol, Philadelphia, PA 19104 USA.
RP Rosenstein, BS (reprint author), Icahn Sch Med Mt Sinai, Dept Radiat Oncol, One Gustave L Levy Pl,Box 1236, New York, NY 10029 USA.
EM barry.rosenstein@mssm.edu
OI Hammerbacher, Jeffrey/0000-0001-6596-8563
FU CCR NIH HHS [HHSN261200800001C]; NCI NIH HHS [HHSN261200800001E, K07
CA187546, R01 CA134444, R01 CA142840, U01 CA187013, U10 CA180822, U10
CA180868, U24 CA180803, UG1 CA189867]
NR 34
TC 3
Z9 3
U1 1
U2 5
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0360-3016
EI 1879-355X
J9 INT J RADIAT ONCOL
JI Int. J. Radiat. Oncol. Biol. Phys.
PD JUL 1
PY 2016
VL 95
IS 3
BP 895
EP 904
DI 10.1016/j.ijrobp.2015.11.009
PG 10
WC Oncology; Radiology, Nuclear Medicine & Medical Imaging
SC Oncology; Radiology, Nuclear Medicine & Medical Imaging
GA DN9AE
UT WOS:000377370600007
PM 26797542
ER
PT J
AU Mayo, CS
Deasy, JO
Chera, BS
Freymann, J
Kirby, JS
Hardenberg, PH
AF Mayo, Charles S.
Deasy, Joseph O.
Chera, Bhishamjit S.
Freymann, John
Kirby, Justin S.
Hardenberg, Patricia H.
TI How Can We Effect Culture Change Toward Data-Driven Medicine?
SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
LA English
DT Editorial Material
ID CLINICIAN; TRIALS; PATTERNS; PATIENT; DRUG; CARE
C1 [Mayo, Charles S.] Univ Michigan, Dept Radiat Oncol, 1500 E Med Ctr Dr, Ann Arbor, MI 48109 USA.
[Deasy, Joseph O.] Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA.
[Chera, Bhishamjit S.] Univ North Carolina Hosp, Dept Radiat Oncol, Chapel Hill, NC USA.
[Freymann, John; Kirby, Justin S.] Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Frederick, MD USA.
[Hardenberg, Patricia H.] Shaw Reg Canc Ctr, Edwards, CO USA.
RP Mayo, CS (reprint author), Univ Michigan, Dept Radiat Oncol, 1500 E Med Ctr Dr, Ann Arbor, MI 48109 USA.
EM cmayo@med.umich.edu
NR 26
TC 1
Z9 1
U1 1
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0360-3016
EI 1879-355X
J9 INT J RADIAT ONCOL
JI Int. J. Radiat. Oncol. Biol. Phys.
PD JUL 1
PY 2016
VL 95
IS 3
BP 916
EP 921
DI 10.1016/j.ijrobp.2015.12.355
PG 6
WC Oncology; Radiology, Nuclear Medicine & Medical Imaging
SC Oncology; Radiology, Nuclear Medicine & Medical Imaging
GA DN9AE
UT WOS:000377370600010
PM 27302507
ER
PT J
AU Zhang, Q
Jing, H
Su, HC
AF Zhang, Qian
Jing, Huie
Su, Helen C.
TI Recent Advances in DOCK8 Immunodeficiency Syndrome
SO JOURNAL OF CLINICAL IMMUNOLOGY
LA English
DT Review
DE DOCK8; combined immunodeficiency; hyperimmunoglobulinemia E syndrome;
tissue residen memory T cells (T-RM); cytothripsis; cutaneous virus
infection; somatic reversion; genetics; eczema; food allergy;
hematopoietic stem cell transplantation
ID STEM-CELL TRANSPLANTATION; CYTOKINESIS 8 DEFICIENCY; HYPER-IGE SYNDROME;
BONE-MARROW-TRANSPLANTATION; WISKOTT-ALDRICH SYNDROME; T-CELLS;
DOCK8-DEFICIENT PATIENTS; PROTECTIVE IMMUNITY; DEDICATOR; PHENOTYPE
AB Since the discovery of the genetic basis of DOCK8 immunodeficiency syndrome (DIDS) in 2009, several hundred patients worldwide have been reported, validating and extending the initial clinical descriptions. Importantly, the beneficial role of hematopoietic stem cell transplantation for this disease has emerged, providing impetus for improved diagnosis. Additionally, several groups have further elucidated the biological functions of DOCK8 in the immune system that help explain disease pathogenesis. Here, we summarize these recent developments.
C1 [Zhang, Qian; Jing, Huie; Su, Helen C.] NIAID, Host Def Lab, NIH, Bldg 10CRC,Room 5-3940,10 Ctr Dr,MSC 1456, Bethesda, MD 20892 USA.
[Zhang, Qian] Sidra Med & Res Ctr, Div Translat Med, Doha, Qatar.
RP Su, HC (reprint author), NIAID, Host Def Lab, NIH, Bldg 10CRC,Room 5-3940,10 Ctr Dr,MSC 1456, Bethesda, MD 20892 USA.
EM hsu@niaid.nih.gov
RI Su, Helen/H-9541-2015
OI Su, Helen/0000-0002-5582-9110
FU Intramural Research Program, NIH, National Institute of Allergy and
Infectious Diseases
FX This work was supported by the Intramural Research Program, NIH,
National Institute of Allergy and Infectious Diseases. Data in Fig. 2
were generated after obtaining written informed consent from the patient
on an NIAID IRB-approved research protocol.
NR 58
TC 1
Z9 1
U1 3
U2 6
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0271-9142
EI 1573-2592
J9 J CLIN IMMUNOL
JI J. Clin. Immunol.
PD JUL
PY 2016
VL 36
IS 5
BP 441
EP 449
DI 10.1007/s10875-016-0296-z
PG 9
WC Immunology
SC Immunology
GA DN8ZZ
UT WOS:000377370100008
PM 27207373
ER
PT J
AU Patel, EU
Laeyendecker, O
Hsieh, YH
Rothman, RE
Kelen, GD
Quinn, TC
AF Patel, Eshan U.
Laeyendecker, Oliver
Hsieh, Yu-Hsiang
Rothman, Richard E.
Kelen, Gabor D.
Quinn, Thomas C.
TI Parallel declines in HIV and hepatitis C virus prevalence, but not in
herpes simplex virus type 2 infection: A 10-year, serial cross-sectional
study in an inner-city emergency department
SO JOURNAL OF CLINICAL VIROLOGY
LA English
DT Article
DE HIV; Hepatitis C; HCV; Herpes; HSV-2; Emergency department
ID HUMAN-IMMUNODEFICIENCY-VIRUS; INJECTION-DRUG USERS; NUTRITION
EXAMINATION SURVEY; STATES-NATIONAL-HEALTH; UNITED-STATES;
VIRAL-HEPATITIS; TESTING PROGRAM; RISK; CARE; SEROPREVALENCE
AB Background: The Johns Hopkins Hospital Emergency Department (JHHED) has served as an observational window on the HIV epidemic in a socioeconomically depressed, urban population. We previously reported that HIV incidence among JHHED patients is decreasing and that prevalence has declined from 11.4% in 2003-5.6% in 2013.
Objectives: This study sought to observe temporal trends in hepatitis C virus (HCV) and herpes simplex virus type 2 (HSV-2) seroprevalence, which are surrogate markers for parenteral and sexual risk behavior, respectively.
Study design: Identity unlinked-serosurveys were conducted over 6-8 weeks in the adult JHHED in 2003, 2007, and 2013. Excess sera from 10,274 patients, previously tested for HIV, were assayed for HSV-2 and HCV antibodies.
Results: Overall HCV seroprevalence declined steadily from 22.0% in 2003-13.8% in 2013 (Ptrend < 0.01), and was significant by all gender and race strata. Overall HSV-2 prevalence declined from 55.3% in 2003-50.0% in 2013 (P-trend < 0.01), but was non-significant after adjustment for demographics. Among HIV+ individuals <45 years of age, there was a significant decrease in the proportion of individuals with HCV co-infection [without HSV-2] (P-trend = 0.02) from 2003 to 2013, however, there was an increase in individuals with HSV-2 co-infection [without HCV] (P-trend < 0.01).
Discussion: Little change in age-specific HSV-2 prevalence suggests the decrease in HIV prevalence was likely not associated with changes in sexual risk behavior. In addition to clinical interventions, strategies to address sexual health disparities and continued parenteral harm-reduction efforts are needed to further drive the decline in HIV. Published by Elsevier B.V.
C1 [Patel, Eshan U.; Laeyendecker, Oliver; Quinn, Thomas C.] NIAID, Div Intramural Res, NIH, 855 North Wolfe St, Baltimore, MD 21205 USA.
[Hsieh, Yu-Hsiang; Rothman, Richard E.; Kelen, Gabor D.] Johns Hopkins Sch Med, Dept Emergency Med, Baltimore, MD USA.
RP Quinn, TC (reprint author), NIAID, Div Intramural Res, NIH, 855 North Wolfe St, Baltimore, MD 21205 USA.
EM tquinn2@jhmi.edu
OI Rothman, Richard/0000-0002-1017-9505; Kelen, Gabor/0000-0002-3236-8286;
Patel, Eshan/0000-0003-2174-5004
FU Division of Intramural Research; National Institute of Allergy and
Infectious Diseases [K01AI100681]
FX This work was supported by the Division of Intramural Research and
extramural support [K01AI100681] from the National Institute of Allergy
and Infectious Diseases.
NR 38
TC 0
Z9 0
U1 1
U2 2
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1386-6532
EI 1873-5967
J9 J CLIN VIROL
JI J. Clin. Virol.
PD JUL
PY 2016
VL 80
BP 93
EP 97
DI 10.1016/j.jcv.2016.05.003
PG 5
WC Virology
SC Virology
GA DN9HW
UT WOS:000377391100019
PM 27232485
ER
PT J
AU Wu, J
Armstrong, TS
Gilbert, MR
AF Wu, Jing
Armstrong, Terri S.
Gilbert, Mark R.
TI Biology and management of ependymomas
SO NEURO-ONCOLOGY
LA English
DT Article
DE Collaborative Ependymoma Research Network; ependymoma; management;
molecular classification; rare disease
ID CENTRAL-NERVOUS-SYSTEM; SPINAL MYXOPAPILLARY EPENDYMOMAS; MALIGNANT
BRAIN-TUMORS; INTRACRANIAL EPENDYMOMA; ADULT PATIENTS;
IMMUNOHISTOCHEMICAL MARKERS; POSTOPERATIVE CHEMOTHERAPY; INFRATENTORIAL
EPENDYMOMA; REFRACTORY EPENDYMOMA; PROGNOSTIC-FACTORS
AB Ependymomas are rare primary tumors of the central nervous system in children and adults that comprise histologically similar but genetically distinct subgroups. The tumor biology is typically more associated with the site of origin rather than being age-specific. Genetically distinct subgroups have been identified by genomic studies based on locations in classic grade II and III ependymomas. They are supratentorial ependymomas with C11orf95-RELA fusion or YAP1 fusion, infratentorial ependymomas with or without a hypermethylated phenotype (CIMP), and spinal cord ependymomas. Myxopapillary ependymomas and subependymomas have different biology than ependymomas with typical WHO grade II or III histology. Surgery and radiotherapy are the mainstays of treatment, while the role of chemotherapy has not yet been established. An in-depth understanding of tumor biology, developing reliable animal models that accurately reflect tumor molecule features, and high throughput drug screening are essential for developing new therapies. Collaborative efforts between scientists, physicians, and advocacy groups will enhance the translation of laboratory findings into clinical trials. Improvements in disease control underscore the need to incorporate assessment and management of patients' symptoms to ensure that treatment advances translate into improvement in quality of life.
C1 [Wu, Jing; Gilbert, Mark R.] NCI, Neurooncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Armstrong, Terri S.] Univ Texas Hlth Sci Ctr Houston, Dept Family Hlth, Houston, TX 77030 USA.
RP Gilbert, MR (reprint author), NCI, Neurooncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM mark.gilbert@nih.gov
RI Gilbert, Mark/J-7494-2016
OI Gilbert, Mark/0000-0003-2556-9722
NR 79
TC 4
Z9 4
U1 3
U2 6
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1522-8517
EI 1523-5866
J9 NEURO-ONCOLOGY
JI Neuro-Oncology
PD JUL
PY 2016
VL 18
IS 7
BP 902
EP 913
DI 10.1093/neuonc/now016
PG 12
WC Oncology; Clinical Neurology
SC Oncology; Neurosciences & Neurology
GA DN7QZ
UT WOS:000377273700003
PM 27022130
ER
PT J
AU Gonzalez, CE
Venkatraman, VK
An, Y
Landman, BA
Davatzikos, C
Bandaru, VVR
Haughey, NJ
Ferrucci, L
Mielke, MM
Resnick, SM
AF Gonzalez, Christopher E.
Venkatraman, Vijay K.
An, Yang
Landman, Bennett A.
Davatzikos, Christos
Bandaru, Veera Venkata Ratnam
Haughey, Norman J.
Ferrucci, Luigi
Mielke, Michelle M.
Resnick, Susan M.
TI Peripheral sphingolipids are associated with variation in white matter
microstructure in older adults
SO NEUROBIOLOGY OF AGING
LA English
DT Article
DE DTI; Ceramides; Sphingomyelin; White matter; Fractional anisotropy;
Sphingolipids
ID MILD COGNITIVE IMPAIRMENT; ALZHEIMERS-DISEASE; PLASMA SPHINGOMYELINS;
CERAMIDE PRODUCTION; HUMAN BRAIN; CHOLESTEROL; INTEGRITY; DEMENTIA;
DECLINE; METABOLISM
AB Sphingolipids serve important structural and functional roles in cellular membranes and myelin sheaths. Plasma sphingolipids have been shown to predict cognitive decline and Alzheimer's disease. However, the association between plasma sphingolipid levels and brain white matter (WM) microstructure has not been examined. We investigated whether plasma sphingolipids (ceramides and sphingomyelins) were associated with magnetic resonance imaging-based diffusion measures, fractional anisotropy (FA), and mean diffusivity, 10.5 years later in 17 WM regions of 150 cognitively normal adults (mean age 67.2). Elevated ceramide species (C20:0, C22:0, C22:1, and C24:1) were associated with lower FA in multiple WM regions, including total cerebral WM, anterior corona radiata, and the cingulum of the cingulate gyrus. Higher sphingomyelins (C18:1 and C20:1) were associated with lower FA in regions such as the anterior corona radiata and body of the corpus callosum. Furthermore, lower sphingomyelin to ceramide ratios (C22:0, C24:0, and C24:1) were associated with lower FA or higher mean diffusivity in regions including the superior and posterior corona radiata. However, although these associations were significant at the a priori p < 0.05, only associations with some regional diffusion measures for ceramide C22:0 and sphingomyelin C18:1 survived correction for multiple comparisons. These findings suggest plasma sphingolipids are associated with variation in WM microstructure in cognitively normal aging. (C) 2016 Elsevier Inc. All rights reserved.
C1 [Gonzalez, Christopher E.; Venkatraman, Vijay K.; An, Yang; Ferrucci, Luigi; Resnick, Susan M.] NIA, Lab Behav Neurosci, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
[Landman, Bennett A.] Vanderbilt Univ, Inst Imaging Sci, 221 Kirkland Hall, Nashville, TN 37235 USA.
[Landman, Bennett A.] Vanderbilt Univ, Dept Elect Engn, Nashville, TN 37235 USA.
[Davatzikos, Christos] Univ Penn, Dept Radiol, Philadelphia, PA 19104 USA.
[Bandaru, Veera Venkata Ratnam; Haughey, Norman J.] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA.
[Mielke, Michelle M.] Mayo Clin, Dept Hlth Sci Res, Rochester, MN USA.
[Mielke, Michelle M.] Mayo Clin, Dept Neurol, Rochester, MN USA.
RP Mielke, MM (reprint author), Mayo Clin, Div Epidemiol, Dept Hlth Sci Res, 200 First St South West, Rochester, MN 55905 USA.
EM mielke.michelle@mayo.edu
FU National Institutes of Health/National Institute on Aging [U01 AG37526];
Intramural Research Program of the National Institute on Aging, NIH
FX This research was supported by a grant from the National Institutes of
Health/National Institute on Aging (U01 AG37526) and by the Intramural
Research Program of the National Institute on Aging, NIH.
NR 47
TC 0
Z9 0
U1 2
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0197-4580
EI 1558-1497
J9 NEUROBIOL AGING
JI Neurobiol. Aging
PD JUL
PY 2016
VL 43
BP 156
EP 163
DI 10.1016/j.neurobiolaging.2016.04.008
PG 8
WC Geriatrics & Gerontology; Neurosciences
SC Geriatrics & Gerontology; Neurosciences & Neurology
GA DN7XI
UT WOS:000377293100016
PM 27255825
ER
PT J
AU Ramos, VFML
Esquenazi, A
Villegas, MAF
Wu, TX
Hallett, M
AF Ramos, Vesper Fe Marie Llaneza
Esquenazi, Alina
Villegas, Monica Anne Faye
Wu, Tianxia
Hallett, Mark
TI Temporal discrimination threshold with healthy aging
SO NEUROBIOLOGY OF AGING
LA English
DT Article
DE Temporal discrimination threshold; Aging; Age effects; Timing; Time
perception
ID PAIRED ASSOCIATIVE STIMULATION; PRIMARY TORSION DYSTONIA; FOCAL HAND
DYSTONIA; HUMAN MOTOR CORTEX; PARKINSONS-DISEASE; INTRACORTICAL
INHIBITION; CORTICAL EXCITABILITY; SOMATOSENSORY CORTEX; PSYCHOGENIC
DYSTONIA; ABNORMAL PLASTICITY
AB The temporal discrimination threshold (TDT) is the shortest interstimulus interval at which a subject can perceive successive stimuli as separate. To investigate the effects of aging on TDT, we studied tactile TDT using the method of limits with 120% of sensory threshold in each hand for each of 100 healthy volunteers, equally divided among men and women, across 10 age groups, from 18 to 79 years. Linear regression analysis showed that age was significantly related to left-hand mean, right-hand mean, and mean of 2 hands with R-square equal to 0.08, 0.164, and 0.132, respectively. Reliability analysis indicated that the 3 measures had fair-to-good reliability (intraclass correlation coefficient: 0.4-0.8). We conclude that TDT is affected by age and has fair-to-good reproducibility using our technique. Published by Elsevier Inc.
C1 [Ramos, Vesper Fe Marie Llaneza; Esquenazi, Alina; Villegas, Monica Anne Faye; Wu, Tianxia; Hallett, Mark] NIH, Human Motor Control Sect, Bldg 10,Room 7D42,10 Ctr Dr, Bethesda, MD 20892 USA.
RP Ramos, VFML (reprint author), NIH, Human Motor Control Sect, Bldg 10,Room 7D42,10 Ctr Dr, Bethesda, MD 20892 USA.
EM vesper.ramos@yahoo.com
OI Ramos, Vesper Fe Marie/0000-0001-8513-7476
FU BCN Peptides; Dystonia Medical Research Foundation
FX Dr. Ramos received research support from BCN Peptides and was supported
by a fellowship grant from the Dystonia Medical Research Foundation.
NR 56
TC 2
Z9 2
U1 3
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0197-4580
EI 1558-1497
J9 NEUROBIOL AGING
JI Neurobiol. Aging
PD JUL
PY 2016
VL 43
BP 174
EP 179
DI 10.1016/j.neurobiolaging.2016.04.009
PG 6
WC Geriatrics & Gerontology; Neurosciences
SC Geriatrics & Gerontology; Neurosciences & Neurology
GA DN7XI
UT WOS:000377293100018
PM 27255827
ER
PT J
AU Borghero, G
Pugliatti, M
Marrosu, F
Marrosu, MG
Murru, MR
Floris, G
Cannas, A
Occhineri, P
Cau, TB
Loi, D
Ticca, A
Traccis, S
Manera, U
Canosa, A
Moglia, C
Calvo, A
Barberis, M
Brunetti, M
Gibbs, JR
Renton, AE
Errichiello, E
Zoledziewska, M
Mulas, A
Qian, Y
Din, J
Pliner, HA
Traynor, BJ
Chio, A
Logullo, FO
Simone, I
Logroscino, G
Salvi, F
Bartolomei, I
Capasso, M
Caponnetto, C
Mandich, P
Mancardi, G
Origone, P
Conforti, FL
Vita, G
Messina, S
Russo, M
Mora, G
Marinou, K
Sideri, R
Lunetta, C
Penco, S
Mosca, L
Pinter, GL
Corbo, M
Riva, N
Carrera, P
Volanti, P
Tremolizzo, L
Ferrarese, C
Fini, N
Fasano, A
Monsurro, MR
Tedeschi, G
Trojsi, F
Piccirillo, G
Cristillo, V
Mazzini, L
D'Alfonso, S
Bersano, A
Corrado, L
Bagarotti, A
La Bella, V
Spataro, R
Colletti, T
Sabatelli, M
Zollino, M
Conte, A
Luigetti, M
Lattante, S
Marangi, G
Santarelli, M
Petrucci, A
Giannini, F
Battistini, S
Ricci, C
Benigni, M
Restagno, G
Casale, F
Marrali, G
Fuda, G
Ossola, I
Cammarosano, S
Ilardi, A
Bertuzzo, D
Tanel, R
Pisano, F
Costantino, E
Pani, C
Puddu, R
Caredda, C
Piras, V
Tranquilli, S
Cuccu, S
Corongiu, D
Melis, M
Milia, A
Pirisi, A
Parish, LD
Ortu, E
AF Borghero, Giuseppe
Pugliatti, Maura
Marrosu, Francesco
Marrosu, Maria Giovanna
Murru, Maria Rita
Floris, Gianluca
Cannas, Antonino
Occhineri, Patrizia
Cau, Tea B.
Loi, Daniela
Ticca, Anna
Traccis, Sebastiano
Manera, Umberto
Canosa, Antonio
Moglia, Cristina
Calvo, Andrea
Barberis, Marco
Brunetti, Maura
Gibbs, J. Raphael
Renton, Alan E.
Errichiello, Edoardo
Zoledziewska, Magdalena
Mulas, Antonella
Qian, Yong
Din, Jun
Pliner, Hannah A.
Traynor, Bryan J.
Chio, Adriano
Logullo, Francesco O.
Simone, Isabella
Logroscino, Giancarlo
Salvi, Fabrizio
Bartolomei, Ilaria
Capasso, Margherita
Caponnetto, Claudia
Mandich, Paolo
Mancardi, Gianluigi
Origone, Paola
Conforti, Francesca L.
Vita, Giuseppe
Messina, Sonia
Russo, Massimo
Mora, Gabriele
Marinou, Kalliopi
Sideri, Riccardo
Lunetta, Christian
Penco, Silvana
Mosca, Lorena
Pinter, Giuseppe Lauria
Corbo, Massimo
Riva, Nilo
Carrera, Paola
Volanti, Paolo
Tremolizzo, Lucio
Ferrarese, Carlo
Fini, Nicola
Fasano, Antonio
Monsurro, Maria Rosaria
Tedeschi, Gioacchino
Trojsi, Francesca
Piccirillo, Giovanni
Cristillo, Viviana
Mazzini, Letizia
D'Alfonso, Sandra
Bersano, Anna
Corrado, Lucia
Bagarotti, Alessandra
La Bella, Vincenzo
Spataro, Rossella
Colletti, Tiziana
Sabatelli, Mario
Zollino, Marcella
Conte, Amelia
Luigetti, Marco
Lattante, Serena
Marangi, Giuseppe
Santarelli, Marialuisa
Petrucci, Antonio
Giannini, Fabio
Battistini, Stefania
Ricci, Claudia
Benigni, Michele
Restagno, Gabriella
Casale, Federico
Marrali, Giuseppe
Fuda, Giuseppe
Ossola, Irene
Cammarosano, Stefania
Ilardi, Antonio
Bertuzzo, Davide
Tanel, Raffaella
Pisano, Fabrizio
Costantino, Emanuela
Pani, Carla
Puddu, Roberta
Caredda, Carla
Piras, Valeria
Tranquilli, Stefania
Cuccu, Stefania
Corongiu, Daniela
Melis, Maurizio
Milia, Antonio
Pirisi, Angelo
Parish, Leslie D.
Ortu, Enzo
CA ITALSGEN
SARDINALS Consortia
TI TBK1 is associated with ALS and ALS-FTD in Sardinian patients
SO NEUROBIOLOGY OF AGING
LA English
DT Article
DE Amyotrophic lateral sclerosis; Genetics; Sporadic; TBK1
ID AMYOTROPHIC-LATERAL-SCLEROSIS; SEQUENCING DATA
AB Recently, mutations in the TANK-binding kinase 1 (TBK1) gene were identified as a cause for amyotrophic lateral sclerosis (ALS) with or without comorbid frontotemporal dementia. We have assessed the frequency and clinical characteristics of TBK1 mutations in a cohort of ALS patients of Sardinian ancestry. Whole-exome sequencing was performed on Hiseq2000 platform (Illumina). Genome analysis Toolkit was used to align and to code variants according to Human Genome (UCSC hg19). Mutation was confirmed with Sanger sequence. In our screening of 186 Sardinian ALS cases, we found 3 (1.6%) patients carrying 3 distinct novel genetic variants: a nonsynonymous SNV c.1150C>T leading to a p.Arg384Thr change in exon 9; a nonsynonymous SNV c.1331G>A causes a p.Arg444Gln change in exon 11; and a frameshift deletion c.2070delG (p.Met690fs) at the exon 20 of the gene leading to a stop at 693 codon. The latter patients also carried missense mutation c.98C>T of the SQSTM1 gene causing a substitution of an arginine with a valine at the position 33 (p.Arg33Val). All variants were found to be deleterious according to in silico predictions. All cases were apparently sporadic and one of them showed frontotemporal dementia associated to ALS. These mutations were not found in 2 cohorts of 6780 ethnic-matched controls. We have found that TBK1 mutations account for 1.6% of Sardinian ALS cases. Our data support the notion that TBK1 is a novel ALS gene, providing important evidence complementary to the first descriptions. (C) 2016 Elsevier Inc. All rights reserved.
C1 [Borghero, Giuseppe; Marrosu, Francesco; Floris, Gianluca; Cannas, Antonino] Azienda Univ Osped Cagliari, Dept Neurol, Cagliari, Italy.
[Borghero, Giuseppe; Marrosu, Francesco; Floris, Gianluca; Cannas, Antonino] Univ Cagliari, Cagliari, Italy.
[Pugliatti, Maura; Occhineri, Patrizia] Univ Ferrara, Dept Biomed & Surg Sci, Sect Neurol Psychiat & Psychol Sci, I-44100 Ferrara, Italy.
[Marrosu, Maria Giovanna; Murru, Maria Rita] Univ Cagliari, Dept Med Sci, Multiple Sclerosis Ctr, Cagliari, Italy.
[Cau, Tea B.; Loi, Daniela] Azienda Sanit Locale 2, Olbia Tempio, Olbia, Italy.
[Ticca, Anna] Azienda Osped San Francesco, Dept Neurol, Nuoro, Italy.
[Traccis, Sebastiano] Osped Antonio Segni, Dept Neurol, Ozieri, Italy.
[Manera, Umberto; Canosa, Antonio; Moglia, Cristina; Calvo, Andrea; Barberis, Marco; Brunetti, Maura; Errichiello, Edoardo; Chio, Adriano] Univ Turin, Amyotroph Lateral Sclerosis Ctr, Rita Levi Montalcini Dept Neurosci, Turin, Italy.
[Canosa, Antonio] Univ Genoa, Dept Neurosci Ophthalmol Genet Rehabil & Child Hl, Genoa, Italy.
[Calvo, Andrea; Gibbs, J. Raphael; Chio, Adriano] Azienda Osped Univ Citta Salute & Sci, Turin, Italy.
[Renton, Alan E.; Errichiello, Edoardo; Pliner, Hannah A.; Traynor, Bryan J.] NIA, Neuromuscular Dis Res Sect, Neurogenet Lab, Bethesda, MD 20892 USA.
[Zoledziewska, Magdalena] NIA, Mol Genet Sect, Neurogenet Lab, Bethesda, MD 20892 USA.
[Zoledziewska, Magdalena] NIA, Computat Biol Core, Neurogenet Lab, Bethesda, MD 20892 USA.
[Zoledziewska, Magdalena; Mulas, Antonella] CNR, Ist Ric Genet & Biomed, Cagliari, Italy.
[Qian, Yong; Din, Jun] NIA, Genet Lab, NIH, Baltimore, MD 21224 USA.
[Traynor, Bryan J.] Johns Hopkins Univ, Dept Neurol, Brain Sci Inst, Baltimore, MD 21218 USA.
[Chio, Adriano] Neurosci Inst Torino NIT, Turin, Italy.
[Chio, Adriano] CNR, Inst Cognit Sci & Technol, Rome, Italy.
RP Chio, A (reprint author), Univ Turin, Rita Levi Montalcini Dept Neurosci, Turin, Italy.
EM achio@usa.net
RI Mosca, Lorena/K-4015-2016; Lunetta, Christian/K-9214-2016; La Bella,
Vincenzo/H-4532-2012; Battistini, Stefania/N-2596-2015; MANDRIOLI,
JESSICA/K-7235-2016; Moglia, Cristina/K-4142-2016;
OI Marrosu, Maria Giovanna/0000-0003-2334-2081; Mosca,
Lorena/0000-0002-6767-2368; Lunetta, Christian/0000-0002-4788-1875;
Battistini, Stefania/0000-0003-2887-7624; MANDRIOLI,
JESSICA/0000-0002-9244-9782; Moglia, Cristina/0000-0001-7377-7222; Riva,
Nilo/0000-0002-0513-9517; Pliner, Hannah/0000-0003-1484-6501
FU Intramural Research Programs of the US National Institutes of Health
(NIH), National Institute on Aging [Z01-AG000949-02]; Agenzia Italiana
per la Ricerca sulla SLA (ARISLA) (SARDINIALS); Packard Centre for ALS
Research at Johns Hopkins; Fondazione Vialli e Mauro Onlus; European
Community [259867]; Joint Programme-Neurodegenerative Disease Research
(Sophia Project) - Italian Health Ministry; Strength Project - Italian
Ministry of University and Research); Fondazione Mario e Anna Magnetto;
Associazione Piemontese per l'Assistenza alla Sclerosi Laterale
Amiotrfica (APASLA)
FX This work was supported in part by the Intramural Research Programs of
the US National Institutes of Health (NIH), National Institute on Aging
(Z01-AG000949-02). The work was also supported by the Agenzia Italiana
per la Ricerca sulla SLA (ARISLA) (SARDINIALS grant), Packard Centre for
ALS Research at Johns Hopkins, Fondazione Vialli e Mauro Onlus, European
Community's Health Seventh Framework Programme (FP7/2007-2013) under
grant agreement #259867, the Joint Programme-Neurodegenerative Disease
Research (Sophia Project, granted by the Italian Health Ministry, and
Strength Project, granted by the Italian Ministry of University and
Research), the Fondazione Mario e Anna Magnetto, and the Associazione
Piemontese per l'Assistenza alla Sclerosi Laterale Amiotrfica (APASLA).
NR 13
TC 4
Z9 4
U1 12
U2 22
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0197-4580
EI 1558-1497
J9 NEUROBIOL AGING
JI Neurobiol. Aging
PD JUL
PY 2016
VL 43
DI 10.1016/j.neurobiolaging.2016.03.028
PG 5
WC Geriatrics & Gerontology; Neurosciences
SC Geriatrics & Gerontology; Neurosciences & Neurology
GA DN7XI
UT WOS:000377293100019
ER
PT J
AU Nie, XJ
Lowe, DW
Rollins, LG
Bentzley, J
Fraser, JL
Martin, R
Singh, I
Jenkins, D
AF Nie, Xingju
Lowe, Danielle W.
Rollins, Laura Grace
Bentzley, Jessica
Fraser, Jamie L.
Martin, Renee
Singh, Inderjit
Jenkins, Dorothea
TI Sex-specific effects of N-acetylcysteine in neonatal rats treated with
hypothermia after severe hypoxia-ischemia
SO NEUROSCIENCE RESEARCH
LA English
DT Article
DE Neonatal hypoxia ischemia; N-acetylcysteine; Sex; Neuroprotection; Redox
regulation
ID FOCAL CEREBRAL-ISCHEMIA; UNFOLDED PROTEIN RESPONSE; EXPERIMENTAL STROKE;
NITRIC-OXIDE; BRAIN-INJURY; OXIDATIVE STRESS; MODERATE HYPOTHERMIA;
CELL-DEATH; INTRACELLULAR GLUTATHIONE; MATRIX METALLOPROTEINASES
AB Approximately half of moderate to severely hypoxic-ischemic (HI) newborns do not respond to hypothermia, the only proven neuroprotective treatment. N-acetylcysteine (NAC), an antioxidant and glutathione precursor, shows promise for neuroprotection in combination with hypothermia, mitigating post-HI neuroinflammation due to oxidative stress. As mechanisms of HI injury and cell death differ in males and females, sex differences must be considered in translational research of neuroprotection. We assessed the potential toxicity and efficacy of NAC in combination with hypothermia, in male and female neonatal rats after severe HI injury. NAC 50 mg/kg/d administered 1 h after initiation of hypothermia significantly decreased iNOS expression and caspase 3 activation in the injured hemisphere versus hypothermia alone. However, only females treated with hypothermia +NAC 50 mg/kg showed improvement in short-term infarct volumes compared with saline treated animals. Hypothermia alone had no effect in this severe model. When NAC was continued for 6 weeks, significant improvement in long-term neuromotor outcomes over hypothermia treatment alone was observed, controlling for sex. Antioxidants may provide insufficient neuroprotection after HI for neonatal males in the short term, while long-term therapy may benefit both sexes. (C) 2016 The Authors. Published by Elsevier Ireland Ltd.
C1 [Nie, Xingju] Med Univ S Carolina, Ctr Biomed Imaging, 165 Ashley Ave, Charleston, SC 29425 USA.
[Lowe, Danielle W.; Bentzley, Jessica; Singh, Inderjit; Jenkins, Dorothea] Med Univ S Carolina, Dept Pediat, MSC 917,165 Ashley Ave, Charleston, SC 29425 USA.
[Rollins, Laura Grace] Univ Massachusetts, Dept Psychol, 100 Morrissey Blvd, Boston, MA 02125 USA.
[Fraser, Jamie L.] NIH, Med Genet Training Program, Natl Human Genome Res Inst, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Martin, Renee] Med Univ S Carolina, Dept Biostat & Epidemiol, 165 Ashley Ave, Charleston, SC 29425 USA.
RP Jenkins, D (reprint author), Med Univ S Carolina, Dept Pediat, MSC 917,165 Ashley Ave, Charleston, SC 29425 USA.
EM niexi@musc.edu; clarkdw@musc.edu; lgrollins@gmail.com; perkel@musc.edu;
jamie.fraser@nih.gov; hebertrl@musc.edu; singhi@musc.edu; jenkd@musc.edu
FU NIH [NS 054428, NS 022576, NS 037766]
FX This work was supported by NIH grants NS 054428, NS 022576 and NS
037766.
NR 77
TC 1
Z9 1
U1 0
U2 5
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0168-0102
EI 1872-8111
J9 NEUROSCI RES
JI Neurosci. Res.
PD JUL
PY 2016
VL 108
BP 24
EP 33
DI 10.1016/j.neures.2016.01.008
PG 10
WC Neurosciences
SC Neurosciences & Neurology
GA DN7ZK
UT WOS:000377298500004
PM 26851769
ER
PT J
AU Julnes, PS
Auh, S
Krakora, R
Withers, K
Nora, D
Matthews, L
Steinbach, S
Snow, J
Smith, B
Nath, A
Morse, C
Kapetanovic, S
AF Julnes, Peter Siyahhan
Auh, Sungyoung
Krakora, Rebecca
Withers, Keenan
Nora, Diana
Matthews, Lindsay
Steinbach, Sally
Snow, Joseph
Smith, Bryan
Nath, Avindra
Morse, Caryn
Kapetanovic, Suad
TI The Association Between Post-traumatic Stress Disorder and Markers of
Inflammation and Immune Activation in HIV-Infected Individuals With
Controlled Viremia
SO PSYCHOSOMATICS
LA English
DT Article
DE client diagnostic questionnaire; PLWH; immunophenotyping; antiretroviral
therapy; post-traumatic stress; mental health
ID COMORBIDITY SURVEY REPLICATION; DSM-IV DISORDERS; CHILDHOOD
MALTREATMENT; HEALTH OUTCOMES; SUBSTANCE USE; TRAUMA; PREVALENCE;
LEUKOCYTE; SEVERITY; CARE
AB Background: Post-traumatic stress disorder (PTSD) may be associated with chronic immune dysregulation and a proinflammatory state. Among HIV-infected individuals, PTSD is associated with greater morbidity and mortality, but the association with immune dysfunction has not been evaluated. This study explores the association between PTSD and selected markers of inflammation and immune activation in a cohort of HIV-infected, virally-suppressed individuals. Methods: HIV-infected adults who were virologically controlled on antiretroviral medications were recruited through a screening protocol for studies of HIV-related neurocognitive disorders. Each participant underwent blood draws, urine toxicology screen, and completed the Client Diagnostic Questionnaire, a semistructured psychiatric interview. Results: Of 114 eligible volunteers, 72 (63%) were male, 77 (68%) African American, and 34 (30%) participants met criteria for PTSD. Participants with PTSD were more likely to be current smokers (79%) than those without (60%) (p = 0.05). The PTSD cohort had significantly higher total white blood cell counts (5318 and 6404 cellsluL, p = 0.03), absolute neutrophil count (2767 and 3577 cellsluL, p = 0.02), CD8% (43 and 48, p = 0.05), and memory CD8% (70 and 78%, p = 0.04); lower naive CD8% (30 and22%, p = 0.04) and higher rate of high-sensitivity C-reactive protein > 3 mgIL (29 and 20, p = 0.03). Discussion: A high prevalence of PTSD was identified in this cohort of HIV-infected adults who were virally suppressed These results suggest that PTSD may be associated with immune dysregulation even among antiretroviral therapy-adherent HIV-infected individuals.
C1 [Julnes, Peter Siyahhan; Steinbach, Sally; Smith, Bryan; Nath, Avindra] NINDS, Sect Infect Nervous Syst, NIH, Bldg 10,Rm 7C103,MSC 1430, Bethesda, MD 20892 USA.
[Auh, Sungyoung] NIDDK, NIH, Bethesda, MD 20892 USA.
[Krakora, Rebecca; Matthews, Lindsay; Morse, Caryn] NIH, Dept Crit Care Med, Bldg 10, Bethesda, MD 20892 USA.
[Withers, Keenan; Nora, Diana; Snow, Joseph; Kapetanovic, Suad] NIMH, NIH, Bethesda, MD 20892 USA.
[Steinbach, Sally] Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Frederick, MD USA.
[Kapetanovic, Suad] Univ So Calif, Keck Sch Med, Dept Psychiat & Behav Sci, Los Angeles, CA 90033 USA.
RP Julnes, PS (reprint author), NINDS, Sect Infect Nervous Syst, NIH, Bldg 10,Rm 7C103,MSC 1430, Bethesda, MD 20892 USA.
EM peterselim.siyahhanjulnes@nih.gov
OI Morse, Caryn/0000-0002-1177-4365
NR 18
TC 0
Z9 0
U1 0
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0033-3182
J9 PSYCHOSOMATICS
JI Psychosomatics
PD JUL-AUG
PY 2016
VL 57
IS 4
BP 423
EP 430
PG 8
WC Psychiatry; Psychology
SC Psychiatry; Psychology
GA DN7XX
UT WOS:000377294600010
ER
PT J
AU Chesnokova, LS
Valencia, SM
Hutt-Fletcher, LM
AF Chesnokova, Liudmila S.
Valencia, Sarah M.
Hutt-Fletcher, Lindsey M.
TI The BDLF3 gene product of Epstein-Barr virus, gp150, mediates
non-productive binding to heparan sulfate on epithelial cells and only
the binding domain of CD21 is required for infection
SO VIROLOGY
LA English
DT Article
DE Epstein-Barr virus; Glycoprotein 150; Heparan-binding; CD21; Epithelial
cell infection
ID B-CELLS; CONFORMATIONAL-CHANGE; GLYCOPROTEINS GHGL; RECEPTOR CR-2;
LYMPHOCYTE-B; ENTRY; REPLICATION; ATTACHMENT; ALPHA-V-BETA-8;
HERPESVIRUS
AB The cell surface molecules used by Epstein-Barr virus (EBV) to attach to epithelial cells are not well-defined, although when CD21, the B cell receptor for EBV is expressed epithelial cell infection increases disproportionately to the increase in virus bound. Many herpesviruses use low affinity charge interactions with molecules such as heparan sulfate to attach to cells. We report here that the EBV glycoprotein gp150 binds to heparan sulfate proteoglycans, but that attachment via this glycoprotein is not productive of infection. We also report that only the aminoterminal two short consensus repeats of CD21 are required for efficient infection, This supports the hypothesis that, when expressed on an epithelial cell CD21 serves primarily to cluster the major attachment protein gp350 in the virus membrane and enhance access of other important glycoproteins to the epithelial cell surface. (C) 2016 Elsevier Inc. All rights reserved.
C1 Louisiana State Univ, Hlth Sci Ctr, Dept Microbiol & Immunol, Ctr Mol & Tumor Virol, 1501 Kings Highway, Shreveport, LA 71130 USA.
Louisiana State Univ, Hlth Sci Ctr, Feist Weiller Canc Ctr, 1501 Kings Highway, Shreveport, LA 71130 USA.
[Valencia, Sarah M.] NIH, Infect Dis Lab, Bldg 50,Room 6134,50 South Dr,MSC8007, Bethesda, MD 20892 USA.
RP Hutt-Fletcher, LM (reprint author), Louisiana State Univ, Hlth Sci Ctr, Dept Microbiol & Immunol, 1501 Kings Highway, Shreveport, LA 71130 USA.
EM lchesn@lsuhsc.edu; sarah.valencia@nih.gov; lhuttf@lsuhsc.edu
FU Public Health Service grants from the National Institute of Dental and
Craniofacial Research [DE016669, DE019599]
FX This work was supported by Public Health Service grants DE016669 (to
LMH-F) and DE019599 (to SMV) from the National Institute of Dental and
Craniofacial Research. We thank Karl Munger for the gift of the NOK
cells.
NR 54
TC 0
Z9 0
U1 3
U2 3
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0042-6822
J9 VIROLOGY
JI Virology
PD JUL
PY 2016
VL 494
BP 23
EP 28
DI 10.1016/j.virol.2016.04.002
PG 6
WC Virology
SC Virology
GA DN8IA
UT WOS:000377321200003
PM 27061054
ER
PT J
AU Raran-Kurussi, S
Waugh, DS
AF Raran-Kurussi, Sreejith
Waugh, David S.
TI A dual protease approach for expression and affinity purification of
recombinant proteins
SO ANALYTICAL BIOCHEMISTRY
LA English
DT Article
DE Maltose-binding protein; Tobacco etch virus protease; Rhinovirus 3C
protease; His-tag; Affinity chromatography
ID MALTOSE-BINDING PROTEIN; TOBACCO ETCH VIRUS; ESCHERICHIA-COLI; FUSION
PROTEINS; SOLUBILITY; TAGS; SPECIFICITY; INSIGHTS
AB We describe a new method for affinity purification of recombinant proteins using a dual protease protocol. Escherichia coli maltose binding protein (MBP) is employed as an N-terminal tag to increase the yield and solubility of its fusion partners. The MBP moiety is then removed by rhinovirus 3C protease, prior to purification, to yield an N-terminally His(6)-tagged protein. Proteins that are only temporarily rendered soluble by fusing them to MBP are readily identified at this stage because they will precipitate after the MBP tag is removed by 3C protease. The remaining soluble His(6)-tagged protein, if any, is subsequently purified by immobilized metal affinity chromatography (IMAC). Finally, the N-terminal His(6) tag is removed by His(6)-tagged tobacco etch virus (TEV) protease to yield the native recombinant protein, and the His(6)-tagged contaminants are removed by adsorption during a second round of IMAC, leaving only the untagged recombinant protein in the column effluent. The generic strategy described here saves time and effort by removing insoluble aggregates at an early stage in the process while also reducing the tendency of MBP to "stick" to its fusion partners during affinity purification. Published by Elsevier Inc.
C1 [Raran-Kurussi, Sreejith; Waugh, David S.] NCI, Prot Engn Sect, Macromol Crystallog Lab, Ctr Canc Res, Ft Detrick, MD 21702 USA.
RP Waugh, DS (reprint author), NCI, Prot Engn Sect, Macromol Crystallog Lab, Ctr Canc Res, Ft Detrick, MD 21702 USA.
EM waughd@mail.nih.gov
FU Intramural Research Program of the National Institutes of Health (NIH),
National Cancer Institute, Center for Cancer Research
FX We thank Karina Keefe and Danielle Needle for constructing the ChikV
protease and the Ubc9 entry clones, respectively. This project was
funded by the Intramural Research Program of the National Institutes of
Health (NIH), National Cancer Institute, Center for Cancer Research. The
content of this publication does not necessarily reflect the views or
policies of the Department of Health and Human Services, nor does the
mention of trade names, commercial products, or organizations imply
endorsement by the U.S. government. We thank the Biophysics Resource in
the Structural Biophysics Laboratory, Frederick National Laboratory, for
assistance with electrospray ionization mass spectroscopy. The authors
declare that they have no conflicts of interest.
NR 28
TC 0
Z9 0
U1 7
U2 17
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0003-2697
EI 1096-0309
J9 ANAL BIOCHEM
JI Anal. Biochem.
PD JUL 1
PY 2016
VL 504
BP 30
EP 37
DI 10.1016/j.ab.2016.04.006
PG 8
WC Biochemical Research Methods; Biochemistry & Molecular Biology;
Chemistry, Analytical
SC Biochemistry & Molecular Biology; Chemistry
GA DN4RN
UT WOS:000377055000007
PM 27105777
ER
PT J
AU Marcum, ZA
Perera, S
Thorpe, JM
Switzer, GE
Castle, NG
Strotmeyer, ES
Simonsick, EM
Ayonayon, HN
Phillips, CL
Rubin, S
Zucker-Levin, AR
Bauer, DC
Shorr, RI
Kang, YH
Gray, SL
Hanlon, JT
AF Marcum, Zachary A.
Perera, Subashan
Thorpe, Joshua M.
Switzer, Galen E.
Castle, Nicholas G.
Strotmeyer, Elsa S.
Simonsick, Eleanor M.
Ayonayon, Hilsa N.
Phillips, Caroline L.
Rubin, Susan
Zucker-Levin, Audrey R.
Bauer, Douglas C.
Shorr, Ronald I.
Kang, Yihuang
Gray, Shelly L.
Hanlon, Joseph T.
CA Hlth ABC Study
TI Antidepressant Use and Recurrent Falls in Community-Dwelling Older
Adults: Findings From the Health ABC Study
SO ANNALS OF PHARMACOTHERAPY
LA English
DT Article
DE antidepressants; aging; drug-related problems; epidemiology; geriatrics;
outcomes research/analysis; pharmacoepidemiology
ID BODY-COMPOSITION; RISK-FACTOR; PEOPLE; MEDICATION; ASSOCIATIONS;
PERFORMANCE; DEPRESSION; ELDERS; WOMEN
AB Background: Few studies have compared the risk of recurrent falls across various antidepressant agents-using detailed dosage and duration data-among community-dwelling older adults, including those who have a history of a fall/fracture. Objective: To examine the association of antidepressant use with recurrent falls, including among those with a history of falls/fractures, in community-dwelling elders. Methods: This was a longitudinal analysis of 2948 participants with data collected via interview at year 1 from the Health, Aging and Body Composition study and followed through year 7 (19972004). Any antidepressant medication use was self-reported at years 1, 2, 3, 5, and 6 and further categorized as (1) selective serotonin reuptake inhibitors (SSRIs), (2) tricyclic antidepressants, and (3) others. Dosage and duration were examined. The outcome was recurrent falls (>= 2) in the ensuing 12-month period following each medication data collection. Results: Using multivariable generalized estimating equations models, we observed a 48% greater likelihood of recurrent falls in antidepressant users compared with nonusers (adjusted odds ratio [AOR] = 1.48; 95% CI = 1.12-1.96). Increased likelihood was also found among those taking SSRIs (AOR = 1.62; 95% CI = 1.15-2.28), with short duration of use (AOR = 1.47; 95% CI = 1.04-2.00), and taking moderate dosages (AOR = 1.59; 95% CI = 1.15-2.18), all compared with no antidepressant use. Stratified analysis revealed an increased likelihood among users with a baseline history of falls/fractures compared with nonusers (AOR = 1.83; 95% CI = 1.28-2.63). Conclusion: Antidepressant use overall, SSRI use, short duration of use, and moderate dosage were associated with recurrent falls. Those with a history of falls/fractures also had an increased likelihood of recurrent falls.
C1 [Marcum, Zachary A.; Gray, Shelly L.] Univ Washington, Seattle, WA 98102 USA.
[Perera, Subashan; Thorpe, Joshua M.; Switzer, Galen E.; Castle, Nicholas G.; Strotmeyer, Elsa S.; Kang, Yihuang; Hanlon, Joseph T.] Univ Pittsburgh, Pittsburgh, PA USA.
[Thorpe, Joshua M.; Switzer, Galen E.; Hanlon, Joseph T.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA.
[Simonsick, Eleanor M.; Phillips, Caroline L.] NIA, Baltimore, MD 21224 USA.
[Ayonayon, Hilsa N.; Rubin, Susan; Bauer, Douglas C.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Zucker-Levin, Audrey R.] Univ Tennessee, Hlth Sci Ctr, Memphis, TN USA.
[Shorr, Ronald I.] Vet Affairs Med Ctr, Gainesville, FL 32608 USA.
RP Marcum, ZA (reprint author), Univ Washington, Sch Pharm, Dept Pharm, 1959 NE Pacific St,H375G,Box 357630, Seattle, WA 98102 USA.
EM zmarcum@uw.edu
FU National Institute on Aging (NIA) [P30AG024827, T32 AG021885,
K07AG033174, R01AG028050]; National Institutes of Health; NIA
[N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106]; National Institute of
Nursing Research [R01NR012459]
FX The authors disclosed receipt of the following financial support for the
research, authorship, and/or publication of this article: This research
was primarily supported by National Institute on Aging (NIA) grants and
contracts (P30AG024827, T32 AG021885, K07AG033174, R01AG028050). This
research was also supported in part by the Intramural Research program
of the National Institutes of Health and NIA (N01-AG-6-2101,
N01-AG-6-2103, and N01-AG-6-2106) and a National Institute of Nursing
Research grant (R01NR012459).
NR 27
TC 2
Z9 2
U1 5
U2 5
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1060-0280
EI 1542-6270
J9 ANN PHARMACOTHER
JI Ann. Pharmacother.
PD JUL
PY 2016
VL 50
IS 7
BP 525
EP 533
DI 10.1177/1060028016644466
PG 9
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA DN5JO
UT WOS:000377102900001
PM 27066988
ER
PT J
AU Rezgui, R
Blumer, K
Yeoh-Tan, G
Trexler, AJ
Magzoub, M
AF Rezgui, Rachid
Blumer, Katy
Yeoh-Tan, Gilbert
Trexler, Adam J.
Magzoub, Mazin
TI Precise quantification of cellular uptake of cell-penetrating peptides
using fluorescence-activated cell sorting and fluorescence correlation
spectroscopy
SO BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
LA English
DT Article
DE Drug delivery; Cellular uptake; Internalization pathways; Intracellular
distribution; Intracellular degradation; Toxicity threshold
ID HUMAN-IMMUNODEFICIENCY-VIRUS; ARGININE-RICH PEPTIDES; INTRACELLULAR
DELIVERY; CARGO MOLECULES; MEMBRANE; INTERNALIZATION; PROTEINS; PLASMA;
MACROPINOCYTOSIS; TRANSLOCATION
AB Cell-penetrating peptides (CPPs) have emerged as a potentially powerful tool for drug delivery due to their ability to efficiently transport a whole host of biologically active cargoes into cells. Although concerted efforts have shed some light on the cellular internalization pathways of CPPs, quantification of CPP uptake has proved problematic. Here we describe an experimental approach that combines two powerful biophysical techniques, fluorescence activated cell sorting (FACS) and fluorescence correlation spectroscopy (FCS), to directly, accurately and precisely measure the cellular uptake of fluorescently-labeled molecules. This rapid and technically simple approach is highly versatile and can readily be applied to characterize all major CPP properties that normally require multiple assays, including amount taken up by cells (in moles/cell), uptake efficiency, internalization pathways, intracellular distribution, intracellular degradation and toxicity threshold. The FACS-FCS approach provides a means for quantifying any intracellular biochemical entity, whether expressed in the cell or introduced exogenously and transported across the plasma membrane. (C) 2016 The Authors. Published by Elsevier B.V.
C1 [Rezgui, Rachid; Magzoub, Mazin] New York Univ, Biol Program, POB 129188,Saadiyat Isl Campus, Abu Dhabi, U Arab Emirates.
[Blumer, Katy] New York Univ, Phys Program, Abu Dhabi, U Arab Emirates.
[Yeoh-Tan, Gilbert] New York Univ, CGSB, Abu Dhabi, U Arab Emirates.
[Trexler, Adam J.] NHLBI, Lab Mol Biophys, NIH, Bldg 10, Bethesda, MD 20892 USA.
RP Magzoub, M (reprint author), New York Univ, Biol Program, POB 129188,Saadiyat Isl Campus, Abu Dhabi, U Arab Emirates.
EM mazin.magzoub@nyu.edu
FU NYU Abu Dhabi; NYU Abu Dhabi Institute [G1205]; National Institutes of
Health [F31 AG038110]
FX The authors thank Justin Blau (NYU), Andrew Miranker (Yale University)
and Elizabeth Rhoades (Yale University) for comments on the manuscript.
Confocal imaging experiments were carried out using the Core Technology
Platform resources at NYU Abu Dhabi. This work was supported by a
start-up fund for M.M. from NYU Abu Dhabi. Additional support was
provided by NYU Abu Dhabi Institute Grant G1205. A.J.T. received support
from the National Institutes of Health (F31 AG038110).
NR 47
TC 3
Z9 3
U1 9
U2 37
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0005-2736
EI 0006-3002
J9 BBA-BIOMEMBRANES
JI Biochim. Biophys. Acta-Biomembr.
PD JUL
PY 2016
VL 1858
IS 7
BP 1499
EP 1506
DI 10.1016/j.bbamem.2016.03.023
PN A
PG 8
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA DN7CN
UT WOS:000377233000011
PM 27033412
ER
PT J
AU Koshiol, J
Castro, F
Kemp, TJ
Gao, YT
Roa, JC
Wang, BS
Nogueira, L
Araya, JC
Shen, MC
Rashid, A
Hsing, AW
Hildesheim, A
Ferreccio, C
Pfeiffer, RM
Pinto, LA
AF Koshiol, Jill
Castro, Felipe
Kemp, Troy J.
Gao, Yu-Tang
Carlos Roa, Juan
Wang, Bingsheng
Nogueira, Leticia
Carlos Araya, Juan
Shen, Ming-Chang
Rashid, Asif
Hsing, Ann W.
Hildesheim, Allan
Ferreccio, Catterina
Pfeiffer, Ruth M.
Pinto, Ligia A.
TI Association of inflammatory and other immune markers with gallbladder
cancer: Results from two independent case-control studies
SO CYTOKINE
LA English
DT Article
DE Local inflammation; Systemic inflammation; Gallbladder cancer
ID BILIARY-TRACT CANCER; CLINICAL-SIGNIFICANCE; METABOLIC SYNDROME;
SERUM-LEVELS; RISK; CHINA; SHANGHAI; STONES; INFILTRATION; METAANALYSIS
AB Most gallbladder cancer (GBC) cases arise in the context of gallstones, which cause inflammation, but few gallstone patients develop GBC. We explored inflammation/immune-related markers measured in bile and serum in GBC cases compared to gallstone patients to better understand how inflammatory patterns in these two conditions differ. We measured 65 immune-related markers in serum and bile from 41 GBC cases and 127 gallstone patients from Shanghai, China, and calculated age- and sex-adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs) for GBC versus gallstones. We then focused on the markers that were significantly elevated in bile and serum to replicate the findings in serum from 35 GBC cases and 31 gallstone controls from Chile. Comparing the highest versus lowest quantile, 15 markers (23%) were elevated in both serum and bile from GBC versus gallstone patients in the Shanghai study (p <0.05). The strongest OR was for CXCL8 (interleukin-8) in serum (96.8, 95% CI: 11.9-790.2). Of these 15 markers, 6 were also significantly elevated in serum from Chile (CCL20, C -reactive protein, CXCL8, CXCL10, resistin, serum amyloid A). Pooled ORs from Shanghai and Chile for these 6 markers ranged from 7.2 (95% CI: 2.8-18.4) for CXCL10 to 58.2 (95% CI: 12.4-273.0) for CXCL8. GBC is associated with inflammation above and beyond that generated by gallstones alone. This local inflammatory process is reflected systemically. Future longitudinal studies are needed to identify the key players in cancer development, which may guide translational efforts to identify individuals at high risk of developing GBC. Published by Elsevier Ltd.
C1 [Koshiol, Jill; Castro, Felipe; Nogueira, Leticia; Hildesheim, Allan] NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Castro, Felipe] Roche, Real World Data Sci RWD S Oncol, Basel, Switzerland.
[Kemp, Troy J.; Pinto, Ligia A.] Biomed Res Inc, Leidos, Frederick Natl Lab Canc Res, HPV Immunol Lab, Frederick, MD USA.
[Gao, Yu-Tang] Shanghai Canc Inst, Dept Epidemiol, Shanghai, Peoples R China.
[Carlos Roa, Juan; Ferreccio, Catterina] Pontificia Univ Catolica Chile, Sch Med, Alameda 340, Santiago, Chile.
[Carlos Roa, Juan; Ferreccio, Catterina] FONDAP, Adv Ctr Chron Dis ACCDiS, Santiago, Chile.
[Wang, Bingsheng] Fudan Univ, Sch Med, Zhongshan Hosp, Dept Gen Surg, Shanghai 200433, Peoples R China.
[Nogueira, Leticia] Texas Dept State Hlth Serv, Austin, TX USA.
[Carlos Araya, Juan] Hosp Dr Hernan Henriquez Aravena, Temuco, Chile.
[Carlos Araya, Juan] Univ La Frontera, Fac Med, Dept Anat Pathol, Temuco, Chile.
[Shen, Ming-Chang] Fudan Univ, Shanghai Canc Ctr, Dept Pathol, Shanghai 200433, Peoples R China.
[Rashid, Asif] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA.
[Hsing, Ann W.] Stanford Canc Inst, Palo Alto, CA USA.
[Hsing, Ann W.] Stanford Sch Med, Dept Hlth Res & Policy, Palo Alto, CA USA.
[Pfeiffer, Ruth M.] NCI, Div Canc Epidemiol & Genet, Biostat Branch, Bethesda, MD 20892 USA.
RP Koshiol, J (reprint author), 9609 Med Ctr Dr,Rm 6-E212,MSC 9767, Bethesda, MD 20892 USA.
EM koshiolj@mail.nih.gov
FU Intramural Research Program of the National Institutes of Health,
National Cancer Institute, Division of Cancer Epidemiology and Genetics
(DCEG); Office of Research on Women's Health (ORWH)
[CONICYT/FONDAP/15130011]; Fondo Nacional de Investigacion y Desarrollo
en Salud (FONIS) [SA11I2205]
FX We thank the collaborating surgeons and pathologists in Shanghai and the
Gallbladder Cancer Chile Working Group (GBCChWG) in Chile for assistance
with field work, including patient recruitment and pathology review;
Chia-Rong Cheng, Lu Sun, and Kai Wu of the Shanghai Cancer Institute and
Johanna Acevedo and Paz Cook of the Pontificia Universidad Catolica the
for coordinating data and specimen collection; and Shelley Niwa of
Westat and Michael Curry of IMS for support with study and data
management. This work was supported by general funds from the Intramural
Research Program of the National Institutes of Health, National Cancer
Institute, Division of Cancer Epidemiology and Genetics (DCEG) and the
Office of Research on Women's Health (ORWH), CONICYT/FONDAP/15130011,
and Fondo Nacional de Investigacion y Desarrollo en Salud (FONIS)
#SA11I2205. These funding sources had no role in the design and conduct
of the study; collection, management, analysis, and interpretation of
the data; preparation of the manuscript; and decision to submit the
manuscript for publication. DCEG did participate in the review and
approval of the manuscript; however, the study authors functioned as
investigators without direction or interference by DCEG.
NR 35
TC 3
Z9 3
U1 3
U2 5
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 1043-4666
EI 1096-0023
J9 CYTOKINE
JI Cytokine
PD JUL
PY 2016
VL 83
BP 217
EP 225
DI 10.1016/j.cyto.2016.05.003
PG 9
WC Biochemistry & Molecular Biology; Cell Biology; Immunology
SC Biochemistry & Molecular Biology; Cell Biology; Immunology
GA DN7AS
UT WOS:000377228300029
PM 27173614
ER
PT J
AU Stroncek, DF
Ren, JQ
Lee, DW
Tran, M
Frodigh, SE
Sabatino, M
Khuu, H
Merchant, MS
Mackall, CL
AF Stroncek, David F.
Ren, Jiaqiang
Lee, Daniel W.
Minh Tran
Frodigh, Sue Ellen
Sabatino, Marianna
Khuu, Hanh
Merchant, Melinda S.
Mackall, Crystal L.
TI Myeloid cells in peripheral blood mononuclear cell concentrates inhibit
the expansion of chimeric antigen receptor T cells
SO CYTOTHERAPY
LA English
DT Article
DE acute lymphocytic leukemia; adoptive cellular therapy; chimeric antigen
receptor T cells; CD19; GD2; osteosarcoma
ID SUPPRESSOR-CELLS; MALIGNANCY; LEUKEMIA; CANCER
AB Background aims. Autologous chimeric antigen receptor (CAR) T-cell therapies have shown promising clinical outcomes, but T-cell yields have been variable. CD19- and GD2-CART-cell manufacturing records were reviewed to identify sources of variability. Methods. CD19-CAR T cells were used to treat 43 patients with acute lymphocytic leukemia or lymphoma and GD2-CAR T cells to treat eight patients with osteosarcoma and three with neuroblastoma. Both types of CART cells were manufactured using autologous peripheral blood mononuclear cells (PBMC) concentrates and anti-CD3/CD28 beads for T-cell enrichment and simulation. Results. A comparison of the first 6 GD2- and the first 22 CD19-CAR T-cell products manufactured revealed that GD2-CART-cell products contained fewer transduced cells than CD19-CART-cell products (147 +/- 102 x 10(6) vs 1502 +/- 1066 x 10(6); P = 0.0059), and their PBMC concentrates contained more monocytes (31.4 +/- 12.4% vs 18.5 +/- 13.7%; P = 0.019). Among the first 28 CD19-CART-cell products manufactured, four had poor expansion yielding less than 1 x 10(6) transduced T cells per kilogram. When PBMC concentrates from these four patients were compared with the 24 others, PBMC concentrates of poorly expanding products contained greater quantities of monocytes (39.8 +/- 12.9% vs. 15.3 +/- 10.8%, P = 0.0014). Among the patients whose CD19-CART cells expanded poorly, manufacturing for two patients was repeated using cryopreserved PBMC concentrates but incorporating a monocyte depleting plastic adherence step, and an adequate dose of CAR T cells was produced for both patients. Conclusions. Variability in CAR T-cell expansion is due, at least in part, to the contamination of the starting PBMC concentrates with monocytes.
C1 [Stroncek, David F.; Ren, Jiaqiang; Minh Tran; Frodigh, Sue Ellen; Sabatino, Marianna; Khuu, Hanh] NIH, Cell Proc Sect, Dept Transfus Med, Ctr Clin, 10 Ctr Dr MSC 1184,Bldg 10,Room 3C720, Bethesda, MD 20892 USA.
[Lee, Daniel W.; Merchant, Melinda S.; Mackall, Crystal L.] NCI, Pediat Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Stroncek, DF (reprint author), NIH, Cell Proc Sect, Dept Transfus Med, Ctr Clin, 10 Ctr Dr MSC 1184,Bldg 10,Room 3C720, Bethesda, MD 20892 USA.
EM dstroncek@cc.nih.gov
FU NIH, Clinical Center; St. Baldrick's Foundation; Hope from Harper Fund;
NIH, National Cancer Institute
FX We thank the staff of the Cell Processing Section, Department of
Transfusion Medicine, Clinical Center, National Institutes of Health
(NIH) for manufacturing the CART cells. This research was supported by
the Intramural Research Program of the NIH, Clinical Center and National
Cancer Institute. DWL is supported by the St. Baldrick's Foundation with
generous support from the Hope from Harper Fund.
NR 21
TC 3
Z9 3
U1 3
U2 7
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1465-3249
EI 1477-2566
J9 CYTOTHERAPY
JI Cytotherapy
PD JUL
PY 2016
VL 18
IS 7
BP 893
EP 901
DI 10.1016/j.jcyt.2016.04.003
PG 9
WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell
Biology; Hematology; Medicine, Research & Experimental
SC Cell Biology; Biotechnology & Applied Microbiology; Hematology; Research
& Experimental Medicine
GA DN2II
UT WOS:000376886900009
PM 27210719
ER
PT J
AU Mendola, P
Wallace, M
Liu, DP
Robledo, C
Mannisto, T
Grantz, KL
AF Mendola, Pauline
Wallace, Maeve
Liu, Danping
Robledo, Candace
Mannisto, Tuija
Grantz, Katherine L.
TI Air pollution exposure and preeclampsia among US women with and without
asthma
SO ENVIRONMENTAL RESEARCH
LA English
DT Article
DE Preeclampsia; Pregnancy; Hypertension; Asthma; Air pollution
ID HYPERTENSIVE DISORDERS; PREGNANCY; OUTCOMES; TOLUENE; METAANALYSIS;
ASSOCIATION; COHORT
AB Maternal asthma and air pollutants have been independently associated with preeclampsia but rarely studied together. Our objective was to comprehensively evaluate preeclampsia risk based on the interaction of maternal asthma and air pollutants. Preeclampsia and asthma diagnoses, demographic and clinical data came from electronic medical records for 210,508 singleton deliveries. Modified Community Multiscale Air Quality models estimated preconception, first and second trimester and whole pregnancy exposure to: particulate matter (PM) < 2.5 and < 10 mu m, ozone, nitrogen oxides (NOx), sulfur dioxide (SO2) and carbon monoxide (CO); PM2.5 constituents; volatile organic compounds (VOCs) and polycyclic aromatic hydrocarbons (PAHs). Asthma-pollutant interaction adjusted relative risks (RR) and 95% confidence intervals (CI) for preeclampsia were calculated by interquartile range for criteria pollutants and high exposure (>= 75th percentile) for PAHs and VOCs. Asthmatics had higher risk associated with first trimester NO and SO2 and whole pregnancy elemental carbon (EC) exposure than non-asthmatics, but only EC significantly increased risk (RR=1.11, CI:1.03-1.21). Asthmatics also had a 10% increased risk associated with second trimester CO. Significant interactions were observed for nearly all V005 and asthmatics had higher risk during all time windows for benzene, ethylbenzene, m-xylene, o-xylene, p-xylene and toluene while most PAHs did not increase risk. Published by Elsevier Inc.
C1 [Mendola, Pauline; Wallace, Maeve; Robledo, Candace; Mannisto, Tuija; Grantz, Katherine L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Intramural Populat Hlth Res, Epidemiol Branch, Rockville, MD 20852 USA.
[Liu, Danping] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Intramural Populat Hlth Res, Biostat & Bioinformat Branch, Rockville, MD 20852 USA.
[Mannisto, Tuija] Northern Finland Lab Ctr NordLab, Oulu, Finland.
[Mannisto, Tuija] Univ Oulu, Dept Clin Chem, Oulu, Finland.
[Mannisto, Tuija] Oulu Univ Hosp, Med Res Ctr Oulu, POB 500, Oys 90029, Finland.
[Mannisto, Tuija] Univ Oulu, POB 500, Oys 90029, Finland.
[Mannisto, Tuija] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, POB 310, Oulu 90101, Finland.
RP Mendola, P (reprint author), NICHD, NIH, 6100 Executive Blvd,Room 7B03F, Rockville, MD 20852 USA.
EM pauline.mendola@nih.gov
OI Mendola, Pauline/0000-0001-5330-2844; Grantz,
Katherine/0000-0003-0276-8534
FU Intramural Research Program of the National Institutes of Health, Eunice
Kennedy Shriver National Institute of Child Health and Human Development
(NICHD) [HHSN267200603425C, HHSN275200800002I, HHSN27500008]
FX This research was supported by the Intramural Research Program of the
National Institutes of Health, Eunice Kennedy Shriver National Institute
of Child Health and Human Development (NICHD), including funding for the
Consortium on Safe Labor (Contract No. HHSN267200603425C) and the Air
Quality and Reproductive Health Study (Contract No. HHSN275200800002I,
Task Order No. HHSN27500008). This paper has been cleared for
publication by the NICHD but the funding source had no role in the
design, analysis, interpretation or writing of the manuscript.
NR 29
TC 0
Z9 0
U1 5
U2 15
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0013-9351
EI 1096-0953
J9 ENVIRON RES
JI Environ. Res.
PD JUL
PY 2016
VL 148
BP 248
EP 255
DI 10.1016/j.envres.2016.04.004
PG 8
WC Environmental Sciences; Public, Environmental & Occupational Health
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health
GA DM9VC
UT WOS:000376712800025
PM 27085496
ER
PT J
AU Linares, GR
Chiu, CT
Scheuing, L
Leng, Y
Liao, HM
Maric, D
Chuang, DM
AF Linares, Gabriel R.
Chiu, Chi-Tso
Scheuing, Lisa
Leng, Yan
Liao, Hsiao-Mei
Maric, Dragan
Chuang, De-Maw
TI Preconditioning mesenchymal stem cells with the mood stabilizers lithium
and valproic acid enhances therapeutic efficacy in a mouse model of
Huntington's disease
SO EXPERIMENTAL NEUROLOGY
LA English
DT Article
DE Huntington's disease; Intranasal delivery; Lithium; Mesenchymal stem
cells; Mood stabilizers; Preconditioning; Stem cell therapy; Valproic
acid
ID CENTRAL-NERVOUS-SYSTEM; TRAUMATIC BRAIN-INJURY; INTRANASAL DELIVERY;
TRANSGENIC MICE; EXTENDS SURVIVAL; ISCHEMIC-STROKE; MUTANT;
NEUROGENESIS; ANGIOGENESIS; MECHANISMS
AB Huntington's disease (HD) is a fatal neurodegenerative disorder caused by CAG repeat expansions in the huntingtin gene. Although, stem cell-based therapy has emerged as a potential treatment for neurodegenerative diseases, limitations remain, including optimizing delivery to the brain and donor cell loss after transplantation. One strategy to boost cell survival and efficacy is to precondition cells before transplantation. Because the neuroprotective actions of the mood stabilizers lithium and valproic acid (VPA) induce multiple pro-survival signaling pathways, we hypothesized that preconditioning bone marrow-derived mesenchymal stem cells (MSCs) with lithium and VPA prior to intranasal delivery to the brain would enhance their therapeutic efficacy, and thereby facilitate functional recovery in N171-82Q HD transgenic mice. MSCs were treated in the presence or absence of combined lithium and VPA, and were then delivered by brain-targeted single intranasal administration to eight-week old HD mice. Histological analysis confirmed the presence of MSCs in the brain. Open-field test revealed that ambulatory distance and mean velocity were significantly improved in HD mice that received preconditioned MSCs, compared to HD vehicle-control and HD mice transplanted with non-preconditioned MSCs. Greater benefits on motor function were observed in HD mice given preconditioned MSCs, while HD mice treated with non-preconditioned MSCs showed no functional benefits. Moreover, preconditioned MSCs reduced striatal neuronal loss and huntingtin aggregates in HD mice. Gene expression profiling of preconditioned MSCs revealed a robust increase in expression of genes involved in trophic effects, antioxidant, anti-apoptosis, cytokine/chemokine receptor, migration, mitochondrial energy metabolism, and stress response signaling pathways. Consistent with this finding, preconditioned MSCs demonstrated increased survival after transplantation into the brain compared to non-preconditioned cells. Our results suggest that preconditioning stem cells with the mood stabilizers lithium and VPA before transplantation may serve as an effective strategy for enhancing the therapeutic efficacy of stem cell-based therapies. (C) 2016 Published by Elsevier Inc.
C1 [Linares, Gabriel R.; Chiu, Chi-Tso; Scheuing, Lisa; Leng, Yan; Liao, Hsiao-Mei; Chuang, De-Maw] NIMH, Mol Neurobiol Sect, NIH, Bldg 10,Room 3D41,10 Ctr Dr MSC 1363, Bethesda, MD 20892 USA.
[Maric, Dragan] NINDS, Flow Cytometry Core Facil, NIH, Bethesda, MD 20892 USA.
RP Linares, GR; Chuang, DM (reprint author), NIMH, Mol Neurobiol Sect, NIH, Bldg 10,Room 3D41,10 Ctr Dr MSC 1363, Bethesda, MD 20892 USA.
EM gabriel.linares@med.usc.edu; chiuc@csr.nih.gov; lscheui@udel.edu;
lengy@mail.nih.gov; hsiao-mei.liao@fda.hhs.gov; maricD@ninds.nih.gov;
chuang@mail.nih.gov
FU National Institute of Mental Health [ZIAMH002468-25]
FX The authors thank Dr. Li-Kai Tsai of National Taiwan University Hospital
for assistance with the preconditioning strategy and Drs. Francis
McMahon and Carolyn Smith of the NIMH for their input in the course of
the study. The authors also thank Peter Leeds of the Molecular
Neurobiology Section/NIMH for editorial assistance. Microscopy imaging
was performed at the Microscopy and Imaging Core (National Institute of
Child Health and Human Development, NIH) with the assistance of Lynne
Holtzclaw and Dr. Vincent Schram. Fluorescence-activated cell sorting
was performed at the Flow Cytometry core facility (National Institute of
Neurological Disorders and Stroke). All other work was performed at the
facilities provided by the National Institutes of Health. We are
grateful for the support of the intramural research program of the
National Institute of Mental Health (ZIAMH002468-25). This work was
written as part of the authors' official duties as Government employees
(affiliated with Annual Report ZIAMH002468). The views expressed in this
article do not necessarily represent the views of the NIMH, NIH, HHS, or
the United States Government.
NR 55
TC 1
Z9 2
U1 5
U2 10
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0014-4886
EI 1090-2430
J9 EXP NEUROL
JI Exp. Neurol.
PD JUL
PY 2016
VL 281
BP 81
EP 92
DI 10.1016/j.expneurol.2016.04.003
PG 12
WC Neurosciences
SC Neurosciences & Neurology
GA DN4RO
UT WOS:000377055100007
PM 27085395
ER
PT J
AU Yang, YC
Lin, XM
Lu, XY
Luo, GJ
Zeng, T
Tang, J
Jiang, F
Li, L
Cui, XL
Huang, WT
Hou, GJ
Chen, X
Ouyang, Q
Tang, SH
Sun, HL
Chen, LN
Gonzalez, FJ
Wu, MC
Cong, WM
Chen, L
Wang, HY
AF Yang, Yingcheng
Lin, Ximeng
Lu, Xinyuan
Luo, Guijuan
Zeng, Tao
Tang, Jing
Jiang, Feng
Li, Liang
Cui, Xiuliang
Huang, Wentao
Hou, Guojun
Chen, Xin
Ouyang, Qing
Tang, Shanhua
Sun, Huanlin
Chen, Luonan
Gonzalez, Frank J.
Wu, Mengchao
Cong, Wenming
Chen, Lei
Wang, Hongyang
TI Interferon-microRNA signalling drives liver precancerous lesion
formation and hepatocarcinogenesis
SO GUT
LA English
DT Article
ID PERSISTENT LCMV INFECTION; HEPATOCELLULAR-CARCINOMA; DYSPLASTIC NODULES;
I INTERFERON; MALIGNANT PROGRESSION; CANCER DEVELOPMENT; KAPPA-B;
INFLAMMATION; ACTIVATION; INTERNALIZATION
AB Objective Precancerous lesion, a well-established histopathologically premalignant tissue with the highest risk for tumourigenesis, develops preferentially from activation of DNA damage checkpoint and persistent inflammation. However, little is known about the mechanisms by which precancerous lesions are initiated and their physiological significance.
Design Laser capture microdissection was used to acquire matched normal liver, precancerous lesion and tumour tissues. miR-484(-/-), Ifnar1(-/-) and Tgfbr2(Delta hep) mice were employed to determine the critical role of the interferon (IFN)-microRNA pathway in precancerous lesion formation and tumourigenesis. RNA immunoprecipitation (RIP), pull-down and chromatin immunoprecipitation (ChIP) assays were applied to explore the underlying mechanisms.
Results miR-484 is highly expressed in over 88% liver samples clinically. DEN-induced precancerous lesions and hepatocellular carcinoma were dramatically impaired in miR-484(-/-) mice. Mechanistically, ectopic expression of miR-484 initiates tumourigenesis and cell malignant transformation through synergistic activation of the transforming growth factor-beta/Gli and nuclear factor-kappa B/type I IFN pathways. Specific acetylation of H3K27 is indispensable for basal IFN-induced continuous transcription of miR-484 and cell transformation. Convincingly, formation of precancerous lesions were significantly attenuated in both Tgfbr2(Delta hep) and Ifnar1(-/-) mice.
Conclusions These findings demonstrate a new protumourigenic axis involving type I IFN-microRNA signalling, providing a potential therapeutic strategy to manipulate or reverse liver precancerous lesions and tumourigenesis.
C1 [Yang, Yingcheng; Lin, Ximeng; Luo, Guijuan; Tang, Jing; Jiang, Feng; Li, Liang; Cui, Xiuliang; Huang, Wentao; Hou, Guojun; Chen, Xin; Ouyang, Qing; Tang, Shanhua; Sun, Huanlin; Chen, Lei; Wang, Hongyang] Second Mil Med Univ, Eastern Hepatobiliary Surg Inst, Int Cooperat Lab Signal Transduct, 225 Changhai Rd, Shanghai 200438, Peoples R China.
[Yang, Yingcheng; Lin, Ximeng; Wu, Mengchao] Eastern Hepatobiliary Surg Hosp, Dept Hepat Surg, Shanghai, Peoples R China.
[Lu, Xinyuan; Cong, Wenming] Second Mil Med Univ, Eastern Hepatobiliary Surg Hosp, Dept Pathol, Shanghai, Peoples R China.
[Luo, Guijuan; Tang, Jing; Li, Liang; Cui, Xiuliang; Chen, Lei; Wang, Hongyang] Natl Ctr Liver Canc, Shanghai, Peoples R China.
[Zeng, Tao; Chen, Luonan] Chinese Acad Sci, Shanghai Inst Biol Sci, Key Lab Syst Biol, Shanghai, Peoples R China.
[Gonzalez, Frank J.; Chen, Lei] NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Wang, Hongyang] Shanghai Jiao Tong Univ, RenJi Hosp, Inst Canc, State Key Lab Oncogenes & Related Genes, Shanghai, Peoples R China.
RP Chen, L; Wang, HY (reprint author), Second Mil Med Univ, Eastern Hepatobiliary Surg Inst, Int Cooperat Lab Signal Transduct, 225 Changhai Rd, Shanghai 200438, Peoples R China.
EM Chenlei@smmu.edu.cn; hywangk@vip.sina.com
FU state Key project for liver cancer [2012ZX10002-009]; National Research
Program of China [2012CB316503, 2012AA02A201]; National Natural Science
Foundation of China [81221061, 81422032, 81272212, 81300306, 81372674,
91529303]; Science Foundation of Shanghai [134119a3700]
FX This work was supported by the state Key project for liver cancer
(2012ZX10002-009), the National Research Program of China (2012CB316503,
2012AA02A201), National Natural Science Foundation of China (81221061,
81422032, 81272212, 81300306, 81372674 and 91529303) and Science
Foundation of Shanghai (134119a3700).
NR 49
TC 2
Z9 2
U1 1
U2 3
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0017-5749
EI 1468-3288
J9 GUT
JI Gut
PD JUL
PY 2016
VL 65
IS 7
BP 1186
EP 1201
DI 10.1136/gutjnl-2015-310318
PG 16
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA DN6GE
UT WOS:000377170200017
PM 26860770
ER
PT J
AU Rutter, CM
Knudsen, AB
Marsh, TL
Doria-Rose, VP
Johnson, E
Pabiniak, C
Kuntz, KM
van Ballegooijen, M
Zauber, AG
Lansdorp-Vogelaar, I
AF Rutter, Carolyn M.
Knudsen, Amy B.
Marsh, Tracey L.
Doria-Rose, V. Paul
Johnson, Eric
Pabiniak, Chester
Kuntz, Karen M.
van Ballegooijen, Marjolein
Zauber, Ann G.
Lansdorp-Vogelaar, Iris
TI Validation of Models Used to Inform Colorectal Cancer Screening
Guidelines: Accuracy and Implications
SO MEDICAL DECISION MAKING
LA English
DT Article
DE colorectal cancer; preventive medicine; gastroenterology; discrete event
simulation; simulation methods
ID SERVICES TASK-FORCE; COST-EFFECTIVENESS; FLEXIBLE SIGMOIDOSCOPY;
MEDICARE POPULATION; BOWEL PREPARATION; COLONOSCOPY; COLON; PREVALENCE;
CALIBRATION; STRATEGIES
AB Background. Microsimulation models synthesize evidence about disease processes and interventions, providing a method for predicting long-term benefits and harms of prevention, screening, and treatment strategies. Because models often require assumptions about unobservable processes, assessing a model's predictive accuracy is important. Methods. We validated 3 colorectal cancer (CRC) microsimulation models against outcomes from the United Kingdom Flexible Sigmoidoscopy Screening (UKFSS) Trial, a randomized controlled trial that examined the effectiveness of one-time flexible sigmoidoscopy screening to reduce CRC mortality. The models incorporate different assumptions about the time from adenoma initiation to development of preclinical and symptomatic CRC. Analyses compare model predictions to study estimates across a range of outcomes to provide insight into the accuracy of model assumptions. Results. All 3 models accurately predicted the relative reduction in CRC mortality 10 years after screening (predicted hazard ratios, with 95% percentile intervals: 0.56 [0.44, 0.71], 0.63 [0.51, 0.75], 0.68 [0.53, 0.83]; estimated with 95% confidence interval: 0.56 [0.45, 0.69]). Two models with longer average preclinical duration accurately predicted the relative reduction in 10-year CRC incidence. Two models with longer mean sojourn time accurately predicted the number of screen-detected cancers. All 3 models predicted too many proximal adenomas among patients referred to colonoscopy. Conclusion. Model accuracy can only be established through external validation. Analyses such as these are therefore essential for any decision model. Results supported the assumptions that the average time from adenoma initiation to development of preclinical cancer is long (up to 25 years), and mean sojourn time is close to 4 years, suggesting the window for early detection and intervention by screening is relatively long. Variation in dwell time remains uncertain and could have important clinical and policy implications.
C1 [Rutter, Carolyn M.] RAND Corp, 1776 Main St, Santa Monica, CA 90401 USA.
[Knudsen, Amy B.] Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA.
[Marsh, Tracey L.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
[Doria-Rose, V. Paul] NCI, Hlth Syst & Intervent Res Branch, Bethesda, MD 20892 USA.
[Johnson, Eric; Pabiniak, Chester] Grp Hlth Res Inst, Seattle, WA USA.
[Kuntz, Karen M.] Univ Minnesota, Sch Publ Hlth, Dept Hlth Policy & Management, Minneapolis, MN USA.
[van Ballegooijen, Marjolein; Lansdorp-Vogelaar, Iris] Erasmus MC, Dept Publ Hlth, Rotterdam, Netherlands.
[Zauber, Ann G.] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA.
RP Rutter, CM (reprint author), RAND Corp, 1776 Main St, Santa Monica, CA 90401 USA.
EM crutter@rand.org
OI Doria-Rose, Vincent/0000-0002-8802-5143
FU National Cancer Institute as part of the Cancer Intervention and
Surveillance Modeling Network (CISNET) [U01-CA-52959]; Center Core Grant
[P30-CA-008748]
FX This publication was made possible by financial support for this study
by a grant from the National Cancer Institute (U01-CA-52959) as part of
the Cancer Intervention and Surveillance Modeling Network (CISNET). The
funding agreement ensured the authors' independence in designing the
study, interpreting the data, writing, and publishing the report. The
contents of this article are solely the responsibility of the authors
and do not necessarily represent the official views of the National
Cancer Institute. For all authors other than Zauber, the entirety of
this work was supported by U01-CA-52959. Zauber was also supported by a
Center Core Grant (P30-CA-008748). Revision accepted for publication 20
October 2015.
NR 46
TC 1
Z9 1
U1 1
U2 1
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0272-989X
EI 1552-681X
J9 MED DECIS MAKING
JI Med. Decis. Mak.
PD JUL
PY 2016
VL 36
IS 5
BP 604
EP 614
DI 10.1177/0272989X15622642
PG 11
WC Health Care Sciences & Services; Medical Informatics
SC Health Care Sciences & Services; Medical Informatics
GA DN5XL
UT WOS:000377144900005
PM 26746432
ER
PT J
AU Ayestaran, FW
Schneider, MF
Kaskel, FJ
Srivaths, PR
Seo-Mayer, PW
Moxey-Mims, M
Furth, SL
Warady, BA
Greenbaum, LA
AF Ayestaran, Frank W.
Schneider, Michael F.
Kaskel, Frederick J.
Srivaths, Poyyapakkam R.
Seo-Mayer, Patricia W.
Moxey-Mims, Marva
Furth, Susan L.
Warady, Bradley A.
Greenbaum, Larry A.
TI Perceived appetite and clinical outcomes in children with chronic kidney
disease
SO PEDIATRIC NEPHROLOGY
LA English
DT Article
DE Nutrition; Pediatric; ER visits; Quality of life; Hospitalization; Renal
function
ID STAGE RENAL-DISEASE; QUALITY-OF-LIFE; HEMODIALYSIS-PATIENTS;
PEDIATRIC-PATIENTS; RISK-FACTORS; GROWTH; NUTRITION; DEATH; DIALYSIS;
INFANTS
AB Children with chronic kidney disease (CKD) may have impaired caloric intake through a variety of mechanisms, with decreased appetite as a putative contributor. In adult CKD, decreased appetite has been associated with poor clinical outcomes. There is limited information about this relationship in pediatric CKD.
A total of 879 participants of the Chronic Kidney Disease in Children (CKiD) study were studied. Self-reported appetite was assessed annually and categorized as very good, good, fair, or poor/very poor. The relationship between appetite and iohexol or estimated glomerular filtration rate (ieGFR), annual changes in anthropometrics z-scores, hospitalizations, emergency room visits, and quality of life were assessed.
An ieGFR < 30 ml/min per 1.73 m(2) was associated with a 4.46 greater odds (95 % confidence interval: 2.80, 7.09) of having a worse appetite than those with ieGFR > 90. Appetite did not predict changes in height, weight, or BMI z-scores. Patients not reporting a very good appetite had more hospitalizations over the next year than those with a very good appetite. Worse appetite was significantly associated with lower parental and patient reported quality of life.
Self-reported appetite in children with CKD worsens with lower ieGFR and is correlated with clinical outcomes, including hospitalizations and quality of life.
C1 [Ayestaran, Frank W.] Emory Univ, Div Pediat Nephrol, 2015 Uppergate Dr NE, Atlanta, GA 30322 USA.
[Ayestaran, Frank W.; Greenbaum, Larry A.] Emory Univ, Atlanta, GA 30322 USA.
[Ayestaran, Frank W.; Greenbaum, Larry A.] Childrens Healthcare Atlanta, Atlanta, GA USA.
[Schneider, Michael F.] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA.
[Kaskel, Frederick J.] Albert Einstein Coll Med, New York, NY USA.
[Srivaths, Poyyapakkam R.] Baylor Coll Med, Houston, TX 77030 USA.
[Srivaths, Poyyapakkam R.] Texas Childrens Hosp, Houston, TX 77030 USA.
[Seo-Mayer, Patricia W.] Pediat Specialists Virginia, Fairfax, VA USA.
[Seo-Mayer, Patricia W.] Georgetown Univ Hosp, Fairfax, VA USA.
[Moxey-Mims, Marva] NIDDK, NIH, Bethesda, MD 20892 USA.
[Furth, Susan L.] Childrens Hosp Penn, Philadelphia, PA USA.
[Furth, Susan L.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Warady, Bradley A.] Childrens Mercy Hosp, Kansas City, MO 64108 USA.
RP Ayestaran, FW (reprint author), Emory Univ, Div Pediat Nephrol, 2015 Uppergate Dr NE, Atlanta, GA 30322 USA.; Ayestaran, FW (reprint author), Emory Univ, Atlanta, GA 30322 USA.; Ayestaran, FW (reprint author), Childrens Healthcare Atlanta, Atlanta, GA USA.
EM frankayestar@health.usf.edu
FU National Institute of Diabetes and Digestive and Kidney Diseases; Eunice
Kennedy Shriver National Institute of Child Health and Human
Development; National Heart, Lung, and Blood Institute [U01-DK-66143,
U01-DK-66174, U01DK-082194, U01-DK-66116]; National Center for Advancing
Translational Sciences of the National Institutes of Health
[UL1TR000454]
FX Data in this manuscript were collected by the Chronic Kidney Disease in
Children prospective cohort study (CKiD) with clinical coordinating
centers (Principal Investigators) at Children's Mercy Hospital and the
University of Missouri - Kansas City (Bradley Warady, MD) and Children's
Hospital of Philadelphia (Susan Furth, MD, PhD), Central Biochemistry
Laboratory (George Schwartz, MD) at the University of Rochester Medical
Center, and data coordinating center (Alvaro Munoz, PhD) at the Johns
Hopkins Bloomberg School of Public Health. The CKiD Study is supported
by grants from the National Institute of Diabetes and Digestive and
Kidney Diseases, with additional funding from the Eunice Kennedy Shriver
National Institute of Child Health and Human Development, and the
National Heart, Lung, and Blood Institute (U01-DK-66143, U01-DK-66174,
U01DK-082194, U01-DK-66116). The CKiD website is located at
http://www.statepi.jhsph.edu/ckid. Research at Emory University
supported by the National Center for Advancing Translational Sciences of
the National Institutes of Health under Award Number UL1TR000454. The
content is solely the responsibility of the authors and does not
necessarily represent the official views of the National Institutes of
Health.
NR 25
TC 1
Z9 1
U1 1
U2 2
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0931-041X
EI 1432-198X
J9 PEDIATR NEPHROL
JI Pediatr. Nephrol.
PD JUL
PY 2016
VL 31
IS 7
BP 1121
EP 1127
DI 10.1007/s00467-016-3321-9
PG 7
WC Pediatrics; Urology & Nephrology
SC Pediatrics; Urology & Nephrology
GA DN2XI
UT WOS:000376925900012
PM 26857711
ER
PT J
AU Arnold, B
Mitchell, SA
Lent, L
Mendoza, TR
Rogak, LJ
Barragan, NM
Willis, G
Medina, M
Lechner, S
Penedo, FJ
Harness, JK
Basch, EM
AF Arnold, Benjamin
Mitchell, Sandra A.
Lent, Lauren
Mendoza, Tito R.
Rogak, Lauren J.
Barragan, Natalie M.
Willis, Gordon
Medina, Mauricio
Lechner, Suzanne
Penedo, Frank J.
Harness, Jay K.
Basch, Ethan M.
CA PRO-CTCAE Spanish Translation Ling
TI Linguistic validation of the Spanish version of the National Cancer
Institute's Patient-Reported Outcomes version of the Common Terminology
Criteria for Adverse Events (PRO-CTCAE)
SO SUPPORTIVE CARE IN CANCER
LA English
DT Article
DE Translation; Spanish; PRO-CTCAE; Cancer; Adverse events; Toxicity;
Patient-Reported outcomes
ID TASK-FORCE; TRANSLATION; INSTRUMENTS
AB Purpose The U.S. NCI's PRO-CTCAE is a library of self-report items for assessing symptomatic adverse events in cancer clinical trials from the patient perspective. The aim of this study was to translate and linguistically validate a Spanish version.
Methods PRO-CTCAE's 124 items were translated from English into Spanish using multiple forward and back translations. Native Spanish speakers undergoing cancer treatment were enrolled at six cancer treatment sites. Participants each completed approximately 50 items and were then interviewed using cognitive probes. The interviews were analyzed at the item level by linguistic themes, and responses were examined for evidence of equivalence to English. Items for which >= 20 % of participants experienced difficulties were reviewed, and phrasing was revised and then retested in subsequent interviews. Items where <20 % of respondents experienced difficulties were also reviewed and were considered for rephrasing and retesting.
Results One hundred nine participants from diverse Spanish-speaking countries were enrolled ( 77 in Round 1 and 32 in Round 2). A majority of items were well comprehended in Round 1. Two items presented difficulties in >= 20 % of participants and were revised/retested without further difficulties. Two items presented difficulties in <20 %, and when retested exhibited no further difficulties. Two items presented difficulties in < 20 %, but were not revised due to lack of alternatives. Sixteen items presented difficulties in <= 12 % and were not revised because difficulties were minor.
Conclusions The Spanish PRO-CTCAE has been developed and refined for use in Spanish-speaking populations, with high levels of comprehension and equivalence to the English PRO-CTCAE.
C1 [Arnold, Benjamin; Lent, Lauren] FACITtrans LLC, 381 S Cottage Hill Ave, Elmhurst, IL 60126 USA.
[Mitchell, Sandra A.] NCI, Div Canc Control & Populat Sci, Outcomes Res Branch, 9609 Med Ctr Dr,East Tower,Room 3-448, Rockville, MD 20850 USA.
[Mendoza, Tito R.] Univ Texas MD Anderson Canc Ctr, Dept Symptom Res, 1400 Pressler St,Unit 1450, Houston, TX 77030 USA.
[Rogak, Lauren J.; Barragan, Natalie M.; Basch, Ethan M.] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, 48 Lexington Ave,2nd Floor, New York, NY 10017 USA.
[Willis, Gordon] NCI, Div Canc Control & Populat Sci, Behav Res Program, 9609 Med Ctr Dr, Rockville, MD 20850 USA.
[Medina, Mauricio] NHLBI, Hlth Educ & Digital Informat Disseminat Branch, OSPEEC, NIH, Bldg 10, Bethesda, MD 20892 USA.
[Lechner, Suzanne] Univ Miami, Miller Sch Med, Sylvester Comprehens Canc Ctr, 1120 NW 14 St,C202, Miami, FL 33136 USA.
[Penedo, Frank J.] Northwestern Univ, Feinberg Sch Med, Dept Med Social Sci, 633 N, St Clair, MO USA.
[Harness, Jay K.] St Joseph Hosp, Ctr Canc Prevent & Treatment, 1010 West La Veta Ave,Suite 470, Orange, CA 92868 USA.
[Basch, Ethan M.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Dept Med, Campus Box 7305, Chapel Hill, NC 27599 USA.
RP Mitchell, SA (reprint author), NCI, Div Canc Control & Populat Sci, Outcomes Res Branch, 9609 Med Ctr Dr,East Tower,Room 3-448, Rockville, MD 20850 USA.
EM barnold@facit.org; mitchlls@mail.nih.gov; llent@facit.org;
tmendoza@mdanderson.org; rogakl@mskcc.org; barragan@mskcc.org;
Willisg@mail.nih.gov; mauricio.medina@nih.gov; SLechner@med.miami.edu;
fpenedo@northwestern.edu; jkharness@gmail.com; ebasch@med.unc.edu
FU U.S. National Cancer Institute [HHSN261201000063C]
FX This work was supported by the U.S. National Cancer Institute contract
HHSN261201000063C.
NR 19
TC 1
Z9 1
U1 1
U2 4
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0941-4355
EI 1433-7339
J9 SUPPORT CARE CANCER
JI Support. Care Cancer
PD JUL
PY 2016
VL 24
IS 7
BP 2843
EP 2851
DI 10.1007/s00520-015-3062-5
PG 9
WC Oncology; Health Care Sciences & Services; Rehabilitation
SC Oncology; Health Care Sciences & Services; Rehabilitation
GA DM9II
UT WOS:000376678400005
PM 26838022
ER
PT J
AU Slater, ME
Castle, IJP
Logan, BK
Hingson, RW
AF Slater, Megan E.
Castle, I-Jen P.
Logan, Barry K.
Hingson, Ralph W.
TI Differences in state drug testing and reporting by driver type in US
fatal traffic crashes
SO ACCIDENT ANALYSIS AND PREVENTION
LA English
DT Article
DE Drugged driving; FARS data; Drug testing rates; Marijuana; State
variation
ID INJURED DRIVERS; UNITED-STATES; ALCOHOL; IMPACT; RECOMMENDATIONS;
RESPONSIBILITY; PREVALENCE; CANNABIS; TRENDS; BLOOD
AB Introduction: Driving under the influence of drugs, including marijuana, has become more prevalent in recent years despite local, state, and federal efforts to prevent such increases. The Fatality Analysis Reporting System (FARS) is the primary source of drugged driving data for fatal crashes in the United States but lacks the completeness required to calculate unbiased estimates of drug use among drivers involved in fatal crashes.
Methods: This article uses the 2013 FARS dataset to present differences in state drug testing rates by driver type, driver fault type, and state-level factors; discusses limitations related to analysis and interpretation of drugged driving data; and offers suggestions for improvements that may enable appropriate use of FARS drug testing data in the future.
Results: Results showed that state drug testing rates were highest among drivers who died at the scene of the crash (median = 70.8%) and drivers who died and were at fault in the crash (median = 64.4%). The lowest testing rates were seen among surviving drivers who were not transported to a hospital (median = 14.0%) and surviving drivers who were not at fault in the crash (median = 10.0%). Drug testing rates differed by state blood alcohol content (BAC) testing rate across all driver types and driver fault types, and in general, states that tested a higher percentage of drivers for BAC had higher drug testing rates.
Discussion: Testing rates might be increased through standardization and mandatory testing policies. FARS data users should continue to be cautious about the limitations of using currently available data to quantify drugged driving. More efforts are needed to improve drug testing and reporting practices, and more research is warranted to establish drug concentration levels at which driving skills become impaired. (C) 2016 Elsevier Ltd. All rights reserved.
C1 [Slater, Megan E.; Castle, I-Jen P.] CSR Inc, 4250 Fairfax Dr,Suite 500, Arlington, VA 22203 USA.
[Logan, Barry K.] NMS Labs, 3701 Welsh Rd, Willow Grove, PA 19090 USA.
[Hingson, Ralph W.] NIAAA, 5635 Fishers LN, Rockville, MD 20852 USA.
RP Slater, ME (reprint author), CSR Inc, 4250 Fairfax Dr,Suite 500, Arlington, VA 22203 USA.
EM mslater@csrincorporated.com
FU National Institute on Alcohol Abuse and Alcoholism [HHSN275201300016C]
FX This article is based on a study conducted for the Alcohol Epidemiologic
Data System project funded by the National Institute on Alcohol Abuse
and Alcoholism through contract No. HHSN275201300016C to CSR,
Incorporated. The authors wish to thank Chiung M. Chen (CSR,
Incorporated) for, providing insights and Hunter Barrat (CSR,
Incorporated) for editorial assistance in the preparation of the
manuscript.
NR 33
TC 0
Z9 0
U1 3
U2 6
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0001-4575
EI 1879-2057
J9 ACCIDENT ANAL PREV
JI Accid. Anal. Prev.
PD JUL
PY 2016
VL 92
BP 122
EP 129
DI 10.1016/j.aap.2016.03.015
PG 8
WC Ergonomics; Public, Environmental & Occupational Health; Social
Sciences, Interdisciplinary; Transportation
SC Engineering; Public, Environmental & Occupational Health; Social
Sciences - Other Topics; Transportation
GA DM9NW
UT WOS:000376694000014
PM 27060753
ER
PT J
AU Hartman, RL
Richman, JE
Hayes, CE
Huestis, MA
AF Hartman, Rebecca L.
Richman, Jack E.
Hayes, Charles E.
Huestis, Marilyn A.
TI Drug Recognition Expert (DRE) examination characteristics of cannabis
impairment
SO ACCIDENT ANALYSIS AND PREVENTION
LA English
DT Article
DE Drug Recognition Expert; Drug Evaluation and Classification Program;
Cannabis; Driving; Impairment; THC
ID FIELD SOBRIETY TESTS; MOTOR-VEHICLE CRASHES; CLASSIFICATION PROGRAM;
DRIVING PERFORMANCE; THC INTOXICATION; FREQUENT SMOKERS; MARIJUANA;
ALCOHOL; BLOOD; DRIVERS
AB Background: The Drug Evaluation and Classification Program (DECP) is commonly utilized in driving under the influence (DUI) cases to help determine category(ies) of impairing drug(s) present in drivers. Cannabis, one of the categories, is associated with approximately doubled crash risk. Our objective was to determine the most reliable DECP metrics for identifying cannabis-driving impairment.
Methods: We evaluated 302 toxicologically-confirmed (blood Delta(9)-tetrahydrocannabinol [THC] >= 1 mu g/L) cannabis-only DECP cases, wherein examiners successfully identified cannabis, compared to normative data (302 non-impaired individuals). Physiological measures, pupil size/light reaction, and performance on psychophysical tests (one leg stand [OLS], walk and turn [WAT], finger to nose [FIN], Modified Romberg Balance [MRB]) were included.
Results: Cases significantly differed from controls (p < 0.05) in pulse (increased), systolic blood pressure (elevated), and pupil size (dilated). Blood collection time after arrest significantly decreased THC concentrations; no significant differences were detected between cases with blood THC <5 mu g/Lversus >= 5 mu g/L. The FTN best predicted cannabis impairment (sensitivity, specificity, positive/negative predictive value, and efficiency >= 87.1%) utilizing >= 3 misses as the deciding criterion; MRB eyelid tremors produced >= 86.1% for all diagnostic characteristics. Other strong indicators included OLS sway, >= 2 WAT clues, and pupil rebound dilation. Requiring >= 2/4 of: >= 3 FTN misses, MRB eyelid tremors, >= 2 OLS clues, and/or >= 2 WAT clues produced the best results (all characteristics >= 96.7%).
Conclusions: Blood specimens should be collected as early as possible. The frequently-debated 5 mu g/L blood THC per se cutoff showed limited relevance. Combined observations on psychophysical and eye exams produced the best cannabis-impairment indicators. Published by Elsevier Ltd.
C1 [Hartman, Rebecca L.; Huestis, Marilyn A.] NIDA, Chem & Drug Metab, Intramural Res Program, NIH, 251 Bayview Blvd Ste 200 Rm 05A721, Baltimore, MD 21224 USA.
[Richman, Jack E.] Hingham Police Dept, 212 Cent St, Hingham, MA 02043 USA.
[Hayes, Charles E.] Int Assoc Chiefs Police, 44 Canal Ctr Plaza,Suite 200, Alexandria, VA 22314 USA.
RP Huestis, MA (reprint author), Huestis & Smith Toxicol LLC, 683 Shore Rd, Severna Pk, MD 21146 USA.
EM rebecca.hartman@umaryland.edu; jack.richman@comcast.net;
hayes@theiacp.org; marilyn.huestis@gmail.com
FU Intramural Research Program, National Institute on Drug Abuse, National
Institutes of Health
FX Research was funded [in part] by the Intramural Research Program,
National Institute on Drug Abuse, National Institutes of Health. The
authors would like to recognize the Drug Recognition Expert (DRE) state
coordinators and DREs who provided the cases and controls for this
research, and the International Association of Chiefs of Police for
assisting with the collection and reporting of the data for this
research.
NR 60
TC 2
Z9 2
U1 10
U2 15
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0001-4575
EI 1879-2057
J9 ACCIDENT ANAL PREV
JI Accid. Anal. Prev.
PD JUL
PY 2016
VL 92
BP 219
EP 229
DI 10.1016/j.aap.2016.04.012
PG 11
WC Ergonomics; Public, Environmental & Occupational Health; Social
Sciences, Interdisciplinary; Transportation
SC Engineering; Public, Environmental & Occupational Health; Social
Sciences - Other Topics; Transportation
GA DM9NW
UT WOS:000376694000024
PM 27107471
ER
PT J
AU Briassoulis, G
Keil, MF
Naved, B
Liu, S
Starost, MF
Nesterova, M
Gokarn, N
Batistatos, A
Wu, TJ
Stratakis, CA
AF Briassoulis, George
Keil, Margaret F.
Naved, Bilal
Liu, Sophie
Starost, Matthew F.
Nesterova, Maria
Gokarn, Nirmal
Batistatos, Anna
Wu, T. John
Stratakis, Constantine A.
TI Studies of mice with cyclic AMP-dependent protein kinase (PKA) defects
reveal the critical role of PKA's catalytic subunits in anxiety
SO BEHAVIOURAL BRAIN RESEARCH
LA English
DT Article
DE Anxiety; Amygdala; Protein kinase a; Knockout mice
ID ELEVATED PLUS-MAZE; G-ALPHA-S; CARNEY COMPLEX; REGULATORY SUBUNIT;
BURYING BEHAVIOR; MOUSE-BRAIN; THREAT BIAS; STRESS; EXPRESSION; RATS
AB Cyclic adenosine mono-phosphate-dependent protein kinase (PICA) is critically involved in the regulation of behavioral responses. Previous studies showed that PKA's main regulatory subunit, R1 alpha, is involved in anxiety-like behaviors. The purpose of this study was to determine how the catalytic subunit, C alpha, might affect R1 alpha's function and determine its effects on anxiety-related behaviors.
The marble bury (MB) and elevated plus maze (EPM) tests were used to assess anxiety-like behavior and the hotplate test to assess nociception in wild type (WT) mouse, a Prkar1a heterozygote (Prkar1a(+/-)) mouse with haploinsufficiency for the regulatory subunit (R1 alpha), a Prkaca heterozygote (Prkar1a(+/-)) mouse with haploinsufficiency for the catalytic subunit (C alpha), and a double heterozygote mouse (Prkar1a(+/-)/Prkaca(+/-)) with haploinsufficiency for both R1 alpha and C alpha. We then examined specific brain nuclei involved in anxiety.
Results of MB test showed a genotype effect, with increased anxiety-like behavior in Prkar1a(+/-) and Prkar1a(+/-)/Prkaca(+/-) compared to WT mice. In the EPM, Prkar1a(+/-) spent significantly less time in the open arms, while Prkaca(+/-) and Prkar1a(+/-)/Prkaca(+/-) mice displayed less exploratory behavior compared to WT mice. The loss of one Prkar1a allele was associated with a significant increase in PKA activity in the basolateral (BLA) and central (CeA) amygdala and ventromedial hypothalamus (VMH) in both Prkar1a(+/-) and Prkar1a(+/-)/Prkaca(+/-) mice.
Alterations of PICA activity induced by haploinsufficiency of its main regulatory or most important catalytic subunits result in anxiety-like behaviors. The BLA, CeA, and VMH are implicated in mediating these PICA effects in brain. Published by Elsevier B.V.
C1 [Briassoulis, George; Keil, Margaret F.; Naved, Bilal; Liu, Sophie; Nesterova, Maria; Gokarn, Nirmal; Batistatos, Anna; Stratakis, Constantine A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Endocrinol & Genet, Program Dev Endocrinol & Genet, NIH, Bethesda, MD 20892 USA.
[Briassoulis, George] Univ Crete, Dept Pediat Intens Care, Iraklion, Greece.
[Starost, Matthew F.] ORS, Div Vet Resources, OD, NIH, Bethesda, MD 20892 USA.
[Wu, T. John] Uniformed Serv Univ Hlth Sci, Dept Obstet & Gynecol, Bethesda, MD 20814 USA.
[Wu, T. John] Uniformed Serv Univ Hlth Sci, Ctr Neurosci & Regenerat Med, Bethesda, MD 20814 USA.
RP Keil, MF (reprint author), NICHD, NIH, PDEGEN, 10 Ctr Dr,Bldg 10 CRC,Room 1 E3330, Bethesda, MD 20892 USA.
EM keilm@mail.nih.gov
RI Briassoulis, George/F-6035-2013
FU NICHD, NIH [Z01-HD008920-01]; Uniformed Services University of the
Health Sciences; Office of Naval Research; Department of Pediatrics,
Faculty of Medicine, University of Crete, Heraklion, Crete, Greece
FX We thank Dr. Kitman Tsang, Ms. Florencia Vasta, Ms. Emily Sun, and Ms.
Melissa Tang for their assistance with this project. This work was
supported by NICHD, NIH intramural project Z01-HD008920-01 to Dr. C.A.
Stratakis. This study was supported in part by intramural graduate
student grant from the Uniformed Services University of the Health
Sciences (MFK) and Office of Naval Research (TJW) and, in part, by the
Department of Pediatrics, Faculty of Medicine, University of Crete,
Heraklion, Crete, Greece (GB).
NR 79
TC 1
Z9 1
U1 7
U2 9
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0166-4328
EI 1872-7549
J9 BEHAV BRAIN RES
JI Behav. Brain Res.
PD JUL 1
PY 2016
VL 307
BP 1
EP 10
DI 10.1016/j.bbr.2016.03.001
PG 10
WC Behavioral Sciences; Neurosciences
SC Behavioral Sciences; Neurosciences & Neurology
GA DM7OD
UT WOS:000376549000001
PM 26992826
ER
PT J
AU Renner, M
Feng, R
Springer, D
Chen, MK
Ntamack, A
Espina, A
Saligan, LN
AF Renner, Michael
Feng, Rebekah
Springer, Danielle
Chen, Mei-Kuang
Ntamack, Andre
Espina, Alexandra
Saligan, Leorey N.
TI A murine model of peripheral irradiation-induced fatigue
SO BEHAVIOURAL BRAIN RESEARCH
LA English
DT Article
DE Cancer; Fatigue; Radiation therapy; Murine model; Radiation-induced
fatigue
ID CANCER-RELATED FATIGUE; DEPRESSIVE-LIKE BEHAVIOR; TUMOR-BEARING MICE;
RUNNING-WHEEL; RADIATION-THERAPY; BREAST-CANCER; C57BL/6J MICE; MOUSE
MODEL; CHEMOTHERAPY; LIPOPOLYSACCHARIDE
AB Purpose: Fatigue is the most ubiquitous side effect of cancer treatment, but its etiology remains elusive. Further investigations into cancer-related fatigue pathobiology necessitate the expanded use of animal models. This study describes the development of a murine model of radiation-induced fatigue.
Methods: Voluntary wheel running activity measured fatigue in 5-8 week-old, male C57BL/6 mice before and after gamma irradiation totaling 2400 cGy (3 consecutive days x 800 cGy daily fractionated doses) to the lower abdominal areas. Three trials confirmed fatigue behavior at this dose. Anhedonia, body weight, and hemoglobin were also measured. Gastrointestinal, skeletal muscle, and bone marrow tissue samples were evaluated for signs of damage.
Results: In two validation trials, irradiated mice (trial 1, n = 8; trial 2, n = 8) covered less cumulative distance in kilometers post-irradiation (trial 1, mean = 115.3 +/- 12.3; trial 2, mean = 113.6 +/- 21.8) than sham controls (trial 1, n = 5, mean = 126.3 +/- 5.7, p = 0.05; trial 2, n = 8, mean = 140.9 +/- 25.4, p = 0.02). Decreased mean daily running distance and speed were observed during the last four hours of the dark cycle in irradiated mice compared to controls for two weeks post-irradiation. There were no differences in saccharin preference or hemoglobin levels between groups, no effect of changes in body weight or hemoglobin on wheel running distance, additionally, histology showed no damage to muscle, bone marrow, or gastrointestinal integrity, with the latter confirmed by ELISA.
Conclusion: We characterized a novel mouse model of fatigue caused by peripheral radiation and not associated with anemia, weight changes, or anhedonia. This model provides opportunities for detailed study of the mechanisms of radiation-induced fatigue. Published by Elsevier B.V.
C1 [Renner, Michael; Feng, Rebekah; Ntamack, Andre; Espina, Alexandra; Saligan, Leorey N.] NIH, Natl Inst Nursing Res, Bethesda, MD 20892 USA.
[Springer, Danielle] NHLBI, Murine Phenotyping Core, NIH, Bldg 10, Bethesda, MD 20892 USA.
[Chen, Mei-Kuang] Univ Arizona, Dept Psychol, Tucson, AZ 85721 USA.
RP Saligan, LN (reprint author), NIH, Div Intramural Res, Natl Inst Nursing Res, Bldg 3,Room 5E14, Bethesda, MD 20892 USA.
EM saliganl@mail.nih.gov
OI Chen, Mei-kuang/0000-0002-0407-6788
FU Division of Intramural Research, National Institute of Nursing Research,
National Institutes of Health
FX This research was supported by the Division of Intramural Research,
National Institute of Nursing Research, National Institutes of Health.
NR 46
TC 1
Z9 1
U1 2
U2 5
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0166-4328
EI 1872-7549
J9 BEHAV BRAIN RES
JI Behav. Brain Res.
PD JUL 1
PY 2016
VL 307
BP 218
EP 226
DI 10.1016/j.bbr.2016.03.035
PG 9
WC Behavioral Sciences; Neurosciences
SC Behavioral Sciences; Neurosciences & Neurology
GA DM7OD
UT WOS:000376549000026
PM 27012391
ER
PT J
AU Archier, A
Varoquaux, A
Garrigue, P
Montava, M
Guerin, C
Gabriel, S
Beschmout, E
Morange, I
Fakhry, N
Castinetti, F
Sebag, F
Barlier, A
Loundou, A
Guillet, B
Pacak, K
Taieb, D
AF Archier, Aurelien
Varoquaux, Arthur
Garrigue, Philippe
Montava, Marion
Guerin, Carole
Gabriel, Sophie
Beschmout, Eva
Morange, Isabelle
Fakhry, Nicolas
Castinetti, Frederic
Sebag, Frederic
Barlier, Anne
Loundou, Anderson
Guillet, Benjamin
Pacak, Karel
Taieb, David
TI Prospective comparison of Ga-68-DOTATATE and F-18-FDOPA PET/CT in
patients with various pheochromocytomas and paragangliomas with emphasis
on sporadic cases
SO EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
LA English
DT Article
DE Positron emission tomography; Gallium radioisotopes; Somatostatin;
Paragangliomas; Neuroendocrine
ID GA-68 DOTATATE PET/CT; NECK PARAGANGLIOMAS; EXTRAADRENAL PARAGANGLIOMA;
IMAGING MODALITIES; MR-ANGIOGRAPHY; HEAD; LOCALIZATION; SCINTIGRAPHY;
OSTEOMALACIA; SPECT/CT
AB Purpose Pheochromocytomas/paragangliomas (PHEOs/PGLs) overexpress somatostatin receptors and recent studies have already shown excellent results in the localization of these tumors using Ga-68-labeled somatostatin analogs (Ga-68-DOTA-SSA), especially in patients with germline succinate dehydrogenase subunit B gene (SDHB) mutations and head and neck PGLs (HNPGLs). The value of Ga-68-DOTA-SSA has to be established in sporadic cases, including PHEOs. Thus, the aim of this study was to compare Ga-68-DOTATATE PET/CT, F-18-FDOPA PET/CT, and conventional imaging in patients with various PHEOs/PGLs with a special emphasis on sporadic cases, including those located in the adrenal gland.
Design Ga-68-DOTATATE, F-18-FDOPA PET/CT, and conventional imaging (contrast-enhanced CT and MRI with MR angiography sequences) were prospectively performed in 30 patients (8 with SDHD mutations, 1 with a MAX mutation and 21 sporadic cases) with PHEO/PGL at initial diagnosis or relapse.
Results The patient-based sensitivities were 93 % (28/30), 97 % (29/30), and 93 % (28/30) for Ga-68-DOTATATE PET/CT, F-18-FDOPA PET/CT, and conventional imaging, respectively. The lesion-based sensitivities were 93 % (43/46), 89 % (41/46), and 76 % (35/46) for Ga-68-DOTATATE PET/CT, F-18-FDOPA PET/CT, and conventional imaging respectively (p = 0.042). Ga-68-DOTATATE PET/CT detected a higher number of HNPGLs (30/30) than F-18-FDOPA PET/CT (26/30; p = 0.112) and conventional imaging (24/30; p = 0.024). Ga-68-DOTATATE PET/CT missed two PHEOs of a few millimeters in size and a large recurrent PHEO. One lesion was considered false-positive on Ga-68-DOTATATE PET/CT and corresponded to a typical focal lesion of fibrous dysplasia on MRI. Among the 11 lesions missed by conventional imaging, 7 were detected by conventional imaging with knowledge of the PET results (4 HNPGLs, 2 LNs, and 1 recurrent PHEO).
Conclusion Ga-68-DOTATATE PET/CT is the most sensitive tool in the detection of HNPGLs, especially SDHD-related tumors, which may be very small and fail to concentrate sufficient F-18-FDOPA. The present study further expands the use of Ga-68-DOTATATE for all patients with HNPGLs, regardless of their genotype. Ga-68-DOTATATE PET/CT may be inferior to F-18-FDOPA PET/CT in the detection PHEOs.
C1 [Archier, Aurelien; Garrigue, Philippe; Gabriel, Sophie; Guillet, Benjamin; Taieb, David] Aix Marseille Univ, La Timone & North Univ Hosp, Dept Nucl Med, Marseille, France.
[Archier, Aurelien; Gabriel, Sophie; Taieb, David] Aix Marseille Univ, European Ctr Res Med Imaging, Marseille, France.
[Archier, Aurelien; Taieb, David] INSERM, Inst J Paoli I Calmettes, UMR1068, Marseille Cancerol Res Ctr, Marseille, France.
[Varoquaux, Arthur; Beschmout, Eva] Aix Marseille Univ, Concept Hosp, Dept Med Imaging, Marseille, France.
[Garrigue, Philippe; Guillet, Benjamin] Aix Marseille Univ, La Timone & North Univ Hosp, Dept Radiopharm, Marseille, France.
[Montava, Marion; Fakhry, Nicolas] Aix Marseille Univ, Concept Hosp, Dept Otorhinolaryngol Head & Neck Surg, Marseille, France.
[Guerin, Carole; Sebag, Frederic] Aix Marseille Univ, Concept Hosp, Dept Endocrine Surg, Marseille, France.
[Morange, Isabelle; Castinetti, Frederic] Aix Marseille Univ, Concept Hosp, Dept Endocrinol, Marseille, France.
[Barlier, Anne] Aix Marseille Univ, Concept Hosp, Lab Biochem & Mol Biol, Marseille, France.
[Loundou, Anderson] Aix Marseille Univ, Dept Publ Hlth, Marseille, France.
[Pacak, Karel] Eunice Kennedy Shriver Natl Inst Child Hlth Human, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD 20892 USA.
RP Taieb, D (reprint author), Aix Marseille Univ, La Timone & North Univ Hosp, Dept Nucl Med, Marseille, France.; Taieb, D (reprint author), Aix Marseille Univ, European Ctr Res Med Imaging, Marseille, France.; Taieb, D (reprint author), INSERM, Inst J Paoli I Calmettes, UMR1068, Marseille Cancerol Res Ctr, Marseille, France.
EM david.taieb@ap-hm.fr
OI Barlier, Anne/0000-0002-3740-6173; Castinetti,
Frederic/0000-0002-1808-8800
FU Intramural Research Program of the Assistance Publique-Hopitaux de
Marseille (AP-HM, France)
FX This research was supported by the Intramural Research Program of the
Assistance Publique-Hopitaux de Marseille (AP-HM, France).
NR 30
TC 6
Z9 6
U1 4
U2 8
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1619-7070
EI 1619-7089
J9 EUR J NUCL MED MOL I
JI Eur. J. Nucl. Med. Mol. Imaging
PD JUL
PY 2016
VL 43
IS 7
BP 1248
EP 1257
DI 10.1007/s00259-015-3268-2
PG 10
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA DM3KV
UT WOS:000376246200007
PM 26637204
ER
PT J
AU Smith, S
Rossignol, P
Willis, S
Zannad, F
Mentz, R
Pocock, S
Bisognano, J
Nadim, Y
Geller, N
Ruble, S
Linde, C
AF Smith, S.
Rossignol, P.
Willis, S.
Zannad, F.
Mentz, R.
Pocock, S.
Bisognano, J.
Nadim, Y.
Geller, N.
Ruble, S.
Linde, C.
TI Neural modulation for hypertension and heart failure
SO INTERNATIONAL JOURNAL OF CARDIOLOGY
LA English
DT Review
DE Hypertension; Heart failure; Neural modulation; Renal denervation;
Baroreceptor
ID BAROREFLEX ACTIVATION THERAPY; CARDIAC RESYNCHRONIZATION THERAPY; RENAL
SYMPATHETIC DENERVATION; VAGUS NERVE-STIMULATION; CAROTID BARORECEPTOR
STIMULATION; AUTONOMIC REGULATION THERAPY; DRUG-RESISTANT HYPERTENSION;
LEFT-VENTRICULAR FUNCTION; LOWERS BLOOD-PRESSURE; RHEOS PIVOTAL TRIAL
AB Hypertension (HTN) and heart failure (HF) have a significant global impact on health, and lead to increased morbidity and mortality. Despite recent advances in pharmacologic and device therapy for these conditions, there is a need for additional treatment modalities. Patients with sub-optimally treated HTN have increased risk for stroke, renal failure and heart failure. The outcome of HF patients remains poor despite modern pharmacological therapy and with established device therapies such as CRT and ICDs. Therefore, the potential role of neuromodulation via renal denervation, baro-reflex modulation and vagal stimulation for the treatment of resistant HTN and HF is being explored. In this manuscript, we review current evidence for neuromodulation in relation to established drug and device therapies and how these therapies may be synergistic in achieving therapy goals in patients with treatment resistant HTN and heart failure. We describe lessons learned from recent neuromodulation trials and outline strategies to improve the potential for success in future trials. This review is based on discussions between scientists, clinical trialists, and regulatory representatives at the 11th annual CardioVascular Clinical Trialist Forum in Washington, DC on December 5-7, 2014. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
C1 [Smith, S.; Willis, S.] Ohio State Univ, Wexner Med Ctr, Dept Internal Med, Columbus, OH 43210 USA.
[Smith, S.; Willis, S.] Ohio State Univ, Div Cardiol, Columbus, OH 43210 USA.
[Rossignol, P.; Zannad, F.] Univ Lorraine, CHU, F CRIN INI CRCT, Inserm,CIC 1433, Nancy, France.
[Mentz, R.] Duke Univ, Med Ctr, Dept Med, Div Cardiol, Durham, NC 27710 USA.
[Pocock, S.] Med Stat Unit LSHTM, London, England.
[Bisognano, J.] Univ Rochester, Med Ctr, Dept Med, Cardiol, 601 Elmwood Ave, Rochester, NY 14642 USA.
[Nadim, Y.] CVRx Inc, Minneapolis, MN USA.
[Geller, N.] NHLBI, Off Biostat Res, Div Cardiovasc Sci, NIH, Bldg 10, Bethesda, MD 20892 USA.
[Ruble, S.] Boston Sci CRV, St Paul, MN USA.
[Linde, C.] Karolinska Inst, Inst Internal Med, Stockholm, Sweden.
[Linde, C.] Karolinska Univ Hosp, Dept Cardiol, N205, S-11776 Stockholm, Sweden.
RP Linde, C (reprint author), Karolinska Univ Hosp, Dept Cardiol, N205, S-11776 Stockholm, Sweden.; Smith, S (reprint author), Ohio State Univ, Div Cardiol, 473 West 12th Ave Suite 200, Columbus, OH 43210 USA.
EM sakima.smith@osumc.edu; cecilia.linde@ki.se
FU Robert Wood Johnson Harold Amos Faculty Development Grant; National
Center for Advancing Translational Sciences [TL1TR001069]; Medtonic;
Swedish Heart Lung Foundation [20080498, 20110406]; Stockholm County
Council [20090376, 20110610]; National Institutes of Health
[U10HL110312]; Amgen; AstraZeneca; Bristol-Myers Squibb;
GlaxoSmithKline; Gilead; Novartis; Otsuka; ResMed; Relypsa; Boston
Scientific; Takeda; Boehringer Ingelheim; GE Healthcare; Servier; Bayer;
Johnson and Johnson; Pfizer; CVRx
FX Dr. Smith receives research support from the Robert Wood Johnson Harold
Amos Faculty Development Grant and the National Center for Advancing
Translational Sciences [TL1TR001069] and serves as a consultant to
CareDx. Dr. Linde has received research grants from Medtonic, Consultant
to Vifor, Novartis. Cardio3, St Jude and Biotronik, and Financial
support CL Swedish Heart Lung Foundation [grants 20080498 and 20110406]
and the Stockholm County Council [grants 20090376 and 20110610]. Dr.
Mentz receives research support from the National Institutes of Health
(U10HL110312), Amgen, AstraZeneca, Bristol-Myers Squibb,
GlaxoSmithKline, Gilead, Novartis, Otsuka, and ResMed; honoraria from
HeartWare, Janssen, Luitpold Pharmaceuticals, Novartis, ResMed, and
Thoratec; and has served on an advisory board for Luitpold
Pharmaceuticals, Inc. Dr. Rossignol received fees from Relypsa. Dr.
Zannad has received fees for serving on the board of Boston Scientific;
consulting fees from Novartis, Takeda, AstraZeneca, Boehringer
Ingelheim, GE Healthcare, Relypsa, Servier, Boston Scientific, Bayer,
Johnson and Johnson, and Resmed; and speakers' fees from Pfizer and
AstraZeneca. Dr. Bisognano has received research support and consulting
fees from CVRx. Nadim Yared is an employee of CVRx. Stephen Ruble is an
employee of Boston Scientific. The other authors report no conflicts.
NR 110
TC 2
Z9 2
U1 5
U2 10
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0167-5273
EI 1874-1754
J9 INT J CARDIOL
JI Int. J. Cardiol.
PD JUL 1
PY 2016
VL 214
BP 321
EP 331
DI 10.1016/j.ijcard.2016.03.078
PG 11
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA DL9BG
UT WOS:000375935700091
PM 27085120
ER
PT J
AU Kannan, G
Crawford, JA
Yang, CX
Gressitt, KL
Ihenatu, C
Krasnova, IN
Cadet, JL
Yolken, RH
Severance, EG
Pletnikov, MV
AF Kannan, Geetha
Crawford, Joshua A.
Yang, ChunXia
Gressitt, Kristin L.
Ihenatu, Chinezimuzo
Krasnova, Irina N.
Cadet, Jean Lud
Yolken, Robert H.
Severance, Emily G.
Pletnikov, Mikhail V.
TI Anti-NMDA receptor autoantibodies and associated neurobehavioral
pathology in mice are dependent on age of first exposure to Toxoplasma
gondii
SO NEUROBIOLOGY OF DISEASE
LA English
DT Article
DE NMDAR; Toxoplasma; C1q; Schizophrenia; Autoantibody; Neurodevelopment
ID PREPULSE INHIBITION; COMPLEMENT CASCADE; IMMUNE ACTIVATION; ADOLESCENT
BRAIN; HUMAN-BEHAVIOR; SCHIZOPHRENIA; ENCEPHALITIS; ANTIBODIES;
AMPHETAMINE; MOUSE
AB Background: Toxoplasma gondii is a pathogen implicated in psychiatric disorders. As elevated antibodies to T. gondii are also present in non-symptomatic individuals, we hypothesized that the age during first exposure to the pathogen may affect symptom manifestation. We tested this hypothesis by evaluating neurobehavioral abnormalities and the immune response in mice following adolescent or adult T. gondii infection.
Methods: Mice were infected with T. gondii at postnatal day 33 (adolescent/juvenile) or 61 (adult). At 8 weeks post-infection (wpi), pre-pulse inhibition of the acoustic startle (PPI) in mice administered MK-801 (0.1 and 0.3 mg/kg) and amphetamine (5 and 10 mg/kg) was assessed. Peripheral (anti-T. gondii, C1q-associated IgG and anti-GLUN2 antibodies) and central (C1q and Iba1) markers of the immune response were also evaluated. In addition, regional brain expression of N-methyl-D-aspartate receptor (NMDAR) subunits (GLUN1 and GLUN2A), glutamatergic (vGLUT1, PSD95) and GABAergic (GAD67) markers, and monoamines (DA, NE, 5-HT) and their metabolites were measured.
Results: Juvenile and adult infected mice exhibited opposite effects of MK-801 on PPI, with decreased PPI in juveniles and increased PPI in adults. There was a significantly greater elevation of GLUN2 autoantibodies in juvenile compared to adult-infected mice. In addition, age-dependent differences were found in regional expression of NMDAR subunits and markers of glutamatergic, GABAergic, and monoaminergic systems. Activated microglia and C1q elevations were found in both juvenile- and adult-T. gondii infected mice.
Conclusions: Our study demonstrates that the age at first exposure to T. gondii is an important factor in shaping distinct behavioral and neurobiological abnormalities. Elevation in GLUN2 autoantibodies or complement protein C1q may be a potential underlying mechanism. A better understanding of these age-related differences may lead to more efficient treatments of behavioral disorders associated with T. gondii infection. (C) 2016 Published by Elsevier Inc.
C1 [Kannan, Geetha; Crawford, Joshua A.; Yang, ChunXia; Pletnikov, Mikhail V.] Johns Hopkins Univ, Dept Psychiat & Behav Sci, Sch Med, 600 North Wolfe St, Baltimore, MD 21287 USA.
[Gressitt, Kristin L.; Ihenatu, Chinezimuzo; Yolken, Robert H.; Severance, Emily G.] Johns Hopkins Univ, Dept Pediat, Sch Med, Stanley Div Dev Neurovirol, Baltimore, MD 21287 USA.
[Krasnova, Irina N.; Cadet, Jean Lud] NIDA, Mol Neuropsychiat Res Branch, NIH, 251 Bayview Blvd, Baltimore, MD 21224 USA.
[Pletnikov, Mikhail V.] Johns Hopkins Univ, Sch Med, Mol & Comparat Pathobiol, Baltimore, MD 21287 USA.
[Pletnikov, Mikhail V.] Johns Hopkins Univ, Sch Med, Solomon H Snyder Dept Neurosci, Baltimore, MD 21287 USA.
[Pletnikov, Mikhail V.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Mol Microbiol & Immunol, Baltimore, MD USA.
[Kannan, Geetha] Univ Michigan, Sch Med, Dept Microbiol & Immunol, Med Sci 2 5641, 1150 West Med Ctr Dr, Ann Arbor, MI 48109 USA.
RP Kannan, G (reprint author), Johns Hopkins Univ, Dept Psychiat & Behav Sci, Sch Med, 600 North Wolfe St, Baltimore, MD 21287 USA.; Kannan, G (reprint author), Univ Michigan, Sch Med, Dept Microbiol & Immunol, Med Sci 2 5641, 1150 West Med Ctr Dr, Ann Arbor, MI 48109 USA.
EM KannanG17@gmail.com
OI Ihenatu, Chinezimuzo/0000-0001-9865-646X
FU Stanley Medical Research Institute (SMRI), Chevy Chase, MD, USA; Silvio
O. Conte Grant [MH-094268]
FX The authors would like to thank Dr. Lorraine Jones-Brando for critical
reading of the manuscript. Funding for this work was provided by the
Stanley Medical Research Institute (SMRI), Chevy Chase, MD, USA and the
Silvio O. Conte Grant MH-094268.
NR 50
TC 2
Z9 2
U1 5
U2 8
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0969-9961
EI 1095-953X
J9 NEUROBIOL DIS
JI Neurobiol. Dis.
PD JUL
PY 2016
VL 91
BP 307
EP 314
DI 10.1016/j.nbd.2016.03.005
PG 8
WC Neurosciences
SC Neurosciences & Neurology
GA DL8IL
UT WOS:000375885600026
PM 26969530
ER
PT J
AU Stapleton, LRT
Schetter, CD
Dooley, LN
Guardino, CM
Huynh, J
Paek, C
Clark-Kauffman, E
Schafer, P
Woolard, R
Lanzi, RG
AF Stapleton, Lynlee R. Tanner
Schetter, Christine Dunkel
Dooley, Larissa N.
Guardino, Christine M.
Huynh, Jan
Paek, Cynthia
Clark-Kauffman, Elizabeth
Schafer, Peter
Woolard, Richard
Lanzi, Robin Gaines
CA Community Child Hlth Network
TI The Community Child Health Network Life Stress Interview: a brief
chronic stress measure for community health research
SO ANXIETY STRESS AND COPING
LA English
DT Article
DE Chronic stress; stress measures; Life Stress Interview; community
research; CBPR; parenting stress
ID DEPRESSION; WOMEN; ADVERSITY; VULNERABILITY; RELIABILITY; DISPARITIES;
DISORDERS; MEDIATORS; SYMPTOMS; EVENTS
AB Background and Objectives: Chronic stress is implicated in many theories as a contributor to a wide range of physical and mental health problems. The current study describes the development of a chronic stress measure that was based on the UCLA Life Stress Interview (LSI) and adapted in collaboration with community partners for use in a large community health study of low-income, ethnically diverse parents of infants in the USA (Community Child Health Network [CCHN]). We describe the instrument, its purpose and adaptations, implementation, and results of a reliability study in a subsample of the larger study cohort. Design and Methods: Interviews with 272 mothers were included in the present study. Chronic stress was assessed using the CCHN LSI, an instrument designed for administration by trained community interviewers to assess four domains of chronic stress, each rated by interviewers. Results: Significant correlations ranging from small to moderate in size between chronic stress scores on this measure, other measures of stress, biomarkers of allostatic load, and mental health provide initial evidence of construct and concurrent validity. Reliability data for interviewer ratings are also provided. Conclusions: This relatively brief interview (15 minutes) is available for use and may be a valuable tool for researchers seeking to measure chronic stress reliably and validly in future studies with time constraints.
C1 [Stapleton, Lynlee R. Tanner; Schetter, Christine Dunkel; Dooley, Larissa N.; Guardino, Christine M.; Huynh, Jan; Paek, Cynthia] Univ Calif Los Angeles, Dept Psychol, 1285A Franz Hall, Los Angeles, CA 90095 USA.
[Clark-Kauffman, Elizabeth] NorthShore Univ HealthSyst, 2650 Ridge Ave, Evanston, IL 60201 USA.
[Schafer, Peter] New York Acad Sci, 1216 5th Ave, New York, NY 10029 USA.
[Woolard, Richard] Baby Love Plus Consortium, Mail Serv Ctr Raleigh 1929, Raleigh, NC 27699 USA.
[Lanzi, Robin Gaines] Univ Alabama Birmingham, Sch Publ Hlth, 1665 Univ Blvd,227 RPHB, Birmingham, AL 35294 USA.
[Community Child Hlth Network] Eunice Kennedy Shriver Natl Inst Child Hlth & Hu, NIH, 6100 Execut Blvd, Bethesda, MD 20892 USA.
RP Schetter, CD (reprint author), Univ Calif Los Angeles, Dept Psychol, 1285A Franz Hall, Los Angeles, CA 90095 USA.
EM dunkel@psych.ucla.edu
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development [U HD44207, U HD44219, U HD44226, U HD44245, U HD44253, U
HD54791, U HD54019, U HD44226-05S1, U HD44245-06S1, R03 HD59584];
National Institute for Nursing Research [U NR008929]
FX The Community Child Health Network (CCHN) is a community-based
participatory research network supported through cooperative agreements
with the Eunice Kennedy Shriver National Institute of Child Health and
Human Development [U HD44207, U HD44219, U HD44226, U HD44245, U
HD44253, U HD54791, U HD54019, U HD44226-05S1, U HD44245-06S1, R03
HD59584] and the National Institute for Nursing Research [U NR008929].
NR 44
TC 0
Z9 0
U1 4
U2 5
PU TAYLOR & FRANCIS LTD
PI ABINGDON
PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND
SN 1061-5806
EI 1477-2205
J9 ANXIETY STRESS COPIN
JI Anxiety Stress Coping
PD JUL
PY 2016
VL 29
IS 4
BP 352
EP 366
DI 10.1080/10615806.2015.1058368
PG 15
WC Neurosciences; Psychiatry; Psychology, Multidisciplinary
SC Neurosciences & Neurology; Psychiatry; Psychology
GA DK5KW
UT WOS:000374959800002
ER
PT J
AU Sampson, JN
Matthews, CE
Freedman, LS
Carroll, RJ
Kipnis, V
AF Sampson, Joshua N.
Matthews, Charles E.
Freedman, Laurence S.
Carroll, Raymond J.
Kipnis, Victor
TI Methods to assess measurement error in questionnaires of sedentary
behavior
SO JOURNAL OF APPLIED STATISTICS
LA English
DT Article
DE Measurement error; PDR; questionnaire; sedentary
ID COVARIATE MEASUREMENT ERROR; DIETARY MEASUREMENT ERROR;
PHYSICAL-ACTIVITY; SELF-REPORT; NUTRITIONAL EPIDEMIOLOGY; STRUCTURE
MODELS; VALIDATION; VALIDITY; TIME; RELIABILITY
AB Sedentary behavior has already been associated with mortality, cardiovascular disease, and cancer. Questionnaires are an affordable tool for measuring sedentary behavior in large epidemiological studies. Here, we introduce and evaluate two statistical methods for quantifying measurement error in questionnaires. Accurate estimates are needed for assessing questionnaire quality. The two methods would be applied to validation studies that measure a sedentary behavior by both questionnaire and accelerometer on multiple days. The first method fits a reduced model by assuming the accelerometer is without error, while the second method fits a more complete model that allows both measures to have error. Because accelerometers tend to be highly accurate, we show that ignoring the accelerometer's measurement error, can result in more accurate estimates of measurement error in some scenarios. In this article, we derive asymptotic approximations for the mean-squared error of the estimated parameters from both methods, evaluate their dependence on study design and behavior characteristics, and offer an R package so investigators can make an informed choice between the two methods. We demonstrate the difference between the two methods in a recent validation study comparing previous day recalls to an accelerometer-based ActivPal.
C1 [Sampson, Joshua N.] NCI, DCEG, Biostat Branch, Rockville, MD USA.
[Matthews, Charles E.] NCI, Nutr Epidemiol Branch, DCEG, Rockville, MD USA.
[Freedman, Laurence S.] Gertner Inst, Biostat Unit, Tel Hashomer, Israel.
[Carroll, Raymond J.] Texas A&M Univ, Dept Stat, College Stn, TX 77843 USA.
[Kipnis, Victor] NCI, Biometry Res Grp, DCP, Rockville, MD USA.
RP Sampson, JN (reprint author), NCI, DCEG, Biostat Branch, Rockville, MD USA.
EM joshua.sampson@nih.gov
FU intramural research program at the NIH; National Cancer Institute
[R37-CA057030]
FX This research was supported by the intramural research program at the
NIH (JNS, CEM) and by a grant from the National Cancer Institute,
R37-CA057030 (RJC).
NR 39
TC 0
Z9 0
U1 4
U2 7
PU TAYLOR & FRANCIS LTD
PI ABINGDON
PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND
SN 0266-4763
EI 1360-0532
J9 J APPL STAT
JI J. Appl. Stat.
PD JUL
PY 2016
VL 43
IS 9
BP 1706
EP 1721
DI 10.1080/02664763.2015.1117593
PG 16
WC Statistics & Probability
SC Mathematics
GA DK6AJ
UT WOS:000375002600009
PM 27340315
ER
PT J
AU Nagore, E
Heidenreich, B
Rachakonda, S
Garcia-Casado, Z
Requena, C
Soriano, V
Frank, C
Traves, V
Quecedo, E
Sanjuan-Gimenez, J
Hemminki, K
Landi, MT
Kumar, R
AF Nagore, Eduardo
Heidenreich, Barbara
Rachakonda, Sivaramakrishna
Garcia-Casado, Zaida
Requena, Celia
Soriano, Virtudes
Frank, Christoph
Traves, Victor
Quecedo, Esther
Sanjuan-Gimenez, Josefa
Hemminki, Kari
Landi, Maria Teresa
Kumar, Rajiv
TI TERT promoter mutations in melanoma survival
SO INTERNATIONAL JOURNAL OF CANCER
LA English
DT Article
DE melanoma; TERT promoter mutations; BRAF mutations; disease-free
survival; melanoma-specific survival
ID CUTANEOUS MELANOMA; PROSTATE-CANCER; TELOMERE LENGTH; BLADDER-CANCER;
LUNG-CANCER; POLYMORPHISM; EXPRESSION; RS2853669; RISK; REACTIVATION
AB Despite advances in targeted therapies, the treatment of advanced melanoma remains an exercise in disease management, hence a need for biomarkers for identification of at-risk primary melanoma patients. In this study, we aimed to assess the prognostic value of TERT promoter mutations in primary melanomas. Tumors from 300 patients with stage I/II melanoma were sequenced for TERT promoter and BRAF/NRAS mutations. Cumulative curves were drawn for patients with and without mutations with progression-free and melanoma-specific survival as outcomes. Cox proportional hazard regression models were used to determine the effect of the mutations on survivals. Individually, presence of TERT promoter and BRAF/NRAS mutations associated with poor disease-free and melanoma-specific survival with modification of the effect by the rs2853669 polymorphism within the TERT promoter. Hazard ratio (HR) for simultaneous occurrence of TERT promoter and BRAF/NRAS mutations for disease-free survival was 2.3 (95% CI 1.2-4.4) and for melanoma-specific survival 5.8 (95% CI 1.9-18.3). The effect of the mutations on melanoma-specific survival in noncarriers of variant allele of the polymorphism was significant (HR 4.5, 95% CI 1.4-15.2) but could not be calculated for the carriers due to low number of events. The variant allele per se showed association with increased survival (HR 0.3, 95% CI 0.1-0.9). The data in this study provide preliminary evidence that TERT promoter mutations in combination with BRAF/NRAS mutations can be used to identify patients at risk of aggressive disease and the possibility of refinement of the classification with inclusion of the rs2853669 polymorphism within TERT promoter.
What's new? Mutations in the promoter of the TERT gene lead to increases in telomerase activity, prolonged telomere maintenance, and cell immortality. Such mutations are associated with parameters of adverse outcome in different cancer types, including melanoma. Data from this study shows that in primary melanoma, mutations in the TERT promoter together with mutations in BRAF/NRAS are associated with very poor survival and can be used to identify patients at risk of disease relapse and death. The prognostic value of the mutations is potentially improved through inclusion of a common polymorphism harbored within the TERT promoter.
C1 [Nagore, Eduardo; Requena, Celia] Inst Valenciano Oncol, Dept Dermatol, C Prof Beltran Baguena 8, Valencia 46009, Spain.
[Heidenreich, Barbara; Rachakonda, Sivaramakrishna; Frank, Christoph; Hemminki, Kari; Kumar, Rajiv] German Canc Res Ctr, Div Mol Genet Epidemiol, Heidelberg, Germany.
[Garcia-Casado, Zaida] Inst Valenciano Oncol, Mol Biol Lab, C Prof Beltran Baguena 8, Valencia 46009, Spain.
[Soriano, Virtudes] Inst Valenciano Oncol, Dept Med Oncol, C Prof Beltran Baguena 8, Valencia 46009, Spain.
[Traves, Victor] Inst Valenciano Oncol, Dept Pathol, C Prof Beltran Baguena 8, Valencia 46009, Spain.
[Quecedo, Esther] Hosp Arnau Vilanova Valencia, Dept Dermatol, Valencia, Spain.
[Sanjuan-Gimenez, Josefa] Hosp Arnau Vilanova Valencia, Dept Pathol, Valencia, Spain.
[Hemminki, Kari] Lund Univ, Ctr Primary Hlth Care Res, Malmo, Sweden.
[Landi, Maria Teresa] NCI, US Natl Inst Hlth, Div Epidemiol & Genet, Bethesda, MD 20892 USA.
RP Nagore, E (reprint author), Inst Valenciano Oncol, Dept Dermatol, C Prof Beltran Baguena 8, Valencia 46009, Spain.
EM eduardo_nagore@ono.com
FU TRANSCAN (German Ministry of Education and Science) [01KT1511]
FX Grant sponsor: TRANSCAN (German Ministry of Education and Science);
Grant number: 01KT1511
NR 44
TC 10
Z9 10
U1 1
U2 7
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0020-7136
EI 1097-0215
J9 INT J CANCER
JI Int. J. Cancer
PD JUL 1
PY 2016
VL 139
IS 1
BP 75
EP 84
DI 10.1002/ijc.30042
PG 10
WC Oncology
SC Oncology
GA DJ7HB
UT WOS:000374381400011
PM 26875008
ER
PT J
AU Halec, G
Schmitt, M
Egger, S
Abnet, CC
Babb, C
Dawsey, SM
Flechtenmacher, C
Gheit, T
Hale, M
Holzinger, D
Malekzadeh, R
Taylor, PR
Tommasino, M
Urban, MI
Waterboer, T
Pawlita, M
Sitas, F
AF Halec, Gordana
Schmitt, Markus
Egger, Sam
Abnet, Christian C.
Babb, Chantal
Dawsey, Sanford M.
Flechtenmacher, Christa
Gheit, Tarik
Hale, Martin
Holzinger, Dana
Malekzadeh, Reza
Taylor, Philip R.
Tommasino, Massimo
Urban, Margaret I.
Waterboer, Tim
Pawlita, Michael
Sitas, Freddy
CA InterSCOPE Collaboration
TI Mucosal alpha-papillomaviruses are not associated with esophageal
squamous cell carcinomas: Lack of mechanistic evidence from South
Africa, China and Iran and from a world-wide meta-analysis
SO INTERNATIONAL JOURNAL OF CANCER
LA English
DT Article
DE esophageal cancer; human papillomavirus; HPV RNA; serology;
HPV-transformed phenotype; p16(INK4); meta-analysis
ID RISK HUMAN-PAPILLOMAVIRUS; ACTIVE HPV16 INVOLVEMENT; CERVICAL-CANCER;
VIRAL LOAD; P16(INK4A) EXPRESSION; OROPHARYNGEAL CANCER; P16 EXPRESSION;
DNA MICROARRAY; MULTIPLEX PCR; TRACT TUMORS
AB Epidemiological and mechanistic evidence on the causative role of human papillomaviruses (HPV) in esophageal squamous cell carcinoma (ESCC) is unclear. We retrieved alcohol- and formalin-fixed paraffin-embedded ESCC tissues from 133 patients seropositive for antibodies against HPV early proteins, from high-incidence ESCC regions: South Africa, China and Iran. With rigorous care to prevent nucleic acid contamination, we analyzed these tissues for the presence of 51 mucosotropic human alpha-papillomaviruses by two sensitive, broad-spectrum genotyping methods, and for the markers of HPV-transformed phenotype: (i) HPV16/18 viral loads by quantitative real-time PCR, (ii) type-specific viral mRNA by E6*I/E6 full-length RT-PCR assays and (iii) expression of cellular protein p16(INK4a). Of 118 analyzable ESCC tissues, 10 (8%) were positive for DNA of HPV types: 16 (4 tumors); 33, 35, 45 (1 tumor each); 11 (2 tumors) and 16, 70 double infection (1 tumor). Inconsistent HPV DNA+ findings by two genotyping methods and negativity in qPCR indicated very low viral loads. A single HPV16 DNA+ tumor additionally harbored HPV16 E6*I mRNA but was p16(INK4a) negative (HPV16 E1 seropositive patient). Another HPV16 DNA+ tumor from an HPV16 E6 seropositive patient showed p16(INK4a) upregulation but no HPV16 mRNA. In the tumor tissues of these serologically preselected ESCC patients, we did not find consistent presence of HPV DNA, HPV mRNA or p16(INK4a) upregulation. These results were supported by a meta-analysis of 14 other similar studies regarding HPV-transformation of ESCC. Our study does not support the etiological role of the 51 analyzed mucosotropic HPV types in the ESCC carcinogenesis.
What's new? South Africa, China and Iran are countries with the highest incidences and mortalities of esophageal squamous cell carcinoma (ESCC). Epidemiological studies suggested a causative role for mucosal high-risk human papillomavirus (HPV) types in ESCC, but consistent evidence of viral transformation is missing. Here the authors examined ESCC samples from high-incidence regions and could not detect biological activity of 51 mucosotropic HPV types. This result is surprising as patients were preselected as being seropositive for papillomavirus infection and points to alternative causes of ESCC carcinogenesis.
C1 [Halec, Gordana; Schmitt, Markus; Holzinger, Dana; Waterboer, Tim; Pawlita, Michael] German Canc Res Ctr, Div Mol Diagnost Oncogen Infect, Res Program Infect Inflammat & Canc, Heidelberg, Germany.
[Halec, Gordana] Univ Calif Los Angeles, David Geffen Sch Med, Obstet & Gynecol, Los Angeles, CA 90095 USA.
[Egger, Sam; Sitas, Freddy] NSW Canc Council, Canc Res Div, Sydney, NSW, Australia.
[Abnet, Christian C.; Dawsey, Sanford M.; Taylor, Philip R.] US Natl Canc Inst, Div Canc Epidemiol & Genet, Bethesda, MD USA.
[Babb, Chantal; Urban, Margaret I.] NHLS MRC Canc Epidemiol Res Grp, Natl Hlth Lab Serv, Johannesburg, South Africa.
[Flechtenmacher, Christa] Heidelberg Univ, Inst Pathol, Neuenheimer Feld 220, Heidelberg, Germany.
[Gheit, Tarik; Tommasino, Massimo] Int Agcy Res Canc, Infect & Canc Biol Grp, 150 Cours Albert Thomas, F-69372 Lyon, France.
[Hale, Martin] Natl Hlth Lab Serv, Dept Anat Pathol, Johannesburg, South Africa.
[Hale, Martin; Urban, Margaret I.] Univ Witwatersrand, Fac Hlth Sci, Johannesburg, South Africa.
[Malekzadeh, Reza] Univ Tehran Med Sci, Shariati Hosp, Digest Dis Res Ctr, Tehran, Iran.
[Sitas, Freddy] Univ Sydney, Sch Publ Hlth, Sydney, NSW 2006, Australia.
[Sitas, Freddy] Univ New S Wales, Sch Publ Hlth & Community Med, Sydney, NSW, Australia.
RP Pawlita, M (reprint author), German Canc Res Ctr, Div Mol Diagnost Oncogen Infect, Res Program Infect Inflammat & Canc, Heidelberg, Germany.
EM m.pawlita@dkfz-heidelberg.de
RI Abnet, Christian/C-4111-2015; Waterboer, Tim/G-1252-2010;
OI Abnet, Christian/0000-0002-3008-7843; Babb de Villiers,
Chantal/0000-0003-1334-1819; Pawlita, Michael/0000-0002-4720-8306
FU DKFZ; Roche; Qiagen
FX MP and MS have received research support through co-operation contracts
of DKFZ with Roche and Qiagen in the field of development of HPV
diagnostics. They are inventors on patents owned by DKFZ in the field of
HPV diagnostics. Authors GH, SE, CCA, CB, SMD, CF, TG, MH, DH, RM, PRT,
MT, MIU, TW and FS have no conflict.
NR 98
TC 3
Z9 3
U1 1
U2 21
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0020-7136
EI 1097-0215
J9 INT J CANCER
JI Int. J. Cancer
PD JUL 1
PY 2016
VL 139
IS 1
BP 85
EP 98
DI 10.1002/ijc.29911
PG 14
WC Oncology
SC Oncology
GA DJ7HB
UT WOS:000374381400012
PM 26529033
ER
PT J
AU Chen, W
Park, K
Volkow, ND
Pan, YT
Du, CW
AF Chen, Wei
Park, Kicheon
Volkow, Nora D.
Pan, Yingtian
Du, Congwu
TI Cocaine-Induced Abnormal Cerebral Hemodynamic Responses to Forepaw
Stimulation Assessed by Integrated Multi-Wavelength Spectroimaging and
Laser Speckle Contrast Imaging
SO IEEE JOURNAL OF SELECTED TOPICS IN QUANTUM ELECTRONICS
LA English
DT Article
DE Biomedical optical imaging; blood flow measurement; brain stimulation;
drug delivery
ID RAT SOMATOSENSORY CORTEX; BLOOD-FLOW; FUNCTIONAL ACTIVATION;
QUANTIFICATION; TOMOGRAPHY
AB Simultaneous imaging of cerebral hemodynamic changes in response to functional activation during drug intoxication provides a valuable strategy to assess cocaine-induced neurovascular dysfunction. However, this requires tools with sufficient spatiotemporal resolution and an adequate signal to noise ratio (SNR). Though several technologies have been developed to address this demand during functional brain activation, their spatiotemporal resolution has been compromised to preserve SNR. In this study, we combine spatiotemporal-domain laser speckle contrast analysis and image correlation techniques to integrate the multi-wavelength spectroimaging and laser speckle contrast imaging (MW-LSCI). Experimental results show that optimized spatiotemporal resolution with enhanced SNR were achieved that enabled simultaneous measurement of multiple hemodynamic responses (i.e., Delta HbO(2), Delta HbR, Delta HbT, and Delta CBF) during cocaine administration. Specifically, cocaine-induced functional cerebral hemodynamic changes were accessed by measuring the activation responses to forepaw electrical stimulation at different times after cocaine administration. With an improved spatiotemporal resolution and SNR, the system was able to differentiate the heterogeneity of cocaine's effects on the cerebral vasculature and on tissue metabolism, demonstrating the unique capability of MW-LSCI for various brain functional and pharmacological studies.
C1 [Chen, Wei; Park, Kicheon; Pan, Yingtian; Du, Congwu] SUNY Stony Brook, Dept Biomed Engn, Stony Brook, NY 11794 USA.
[Volkow, Nora D.] Natl Inst Drug Abuse, NIH, Bethesda, MD 20892 USA.
RP Pan, YT; Du, CW (reprint author), SUNY Stony Brook, Dept Biomed Engn, Stony Brook, NY 11794 USA.
EM yingtian.pan@stonybrook.edu; congwu.du@stonybrook.edu
FU National Institutes of Health [R21DA032228, 1R01DA029718, R01NS084817];
NIH's Intramural Program
FX This work was supported in part by the National Institutes of Health
under Grants R21DA032228 (YP/CD), 1R01DA029718 (CD/YP), R01NS084817
(CD/XH), and NIH's Intramural Program (NDV). (Corresponding authors:
Yingtian Pan and Congwu Du.)
NR 22
TC 0
Z9 0
U1 4
U2 21
PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC
PI PISCATAWAY
PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA
SN 1077-260X
EI 1558-4542
J9 IEEE J SEL TOP QUANT
JI IEEE J. Sel. Top. Quantum Electron.
PD JUL-AUG
PY 2016
VL 22
IS 4
AR 6802608
DI 10.1109/JSTQE.2015.2503319
PG 8
WC Engineering, Electrical & Electronic; Optics; Physics, Applied
SC Engineering; Optics; Physics
GA DH8SG
UT WOS:000373066000001
ER
PT J
AU Lee, MS
Lee, B
Park, KE
Utsuki, T
Shin, T
Oh, CW
Kim, HR
AF Lee, Min-Sup
Lee, Bonggi
Park, Kyoung-Eun
Utsuki, Tadanobu
Shin, Taisun
Oh, Chul Woong
Kim, Hyeung-Rak
TI Dieckol enhances the expression of antioxidant and detoxifying enzymes
by the activation of Nrf2-MAPK signaling pathway in HepG2 cells (vol
174, pg 538, 2015)
SO FOOD CHEMISTRY
LA English
DT Correction
C1 [Lee, Min-Sup; Lee, Bonggi; Park, Kyoung-Eun; Kim, Hyeung-Rak] Pukyong Natl Univ, Dept Food Sci & Nutr, Busan 608737, South Korea.
[Lee, Bonggi] NICHHD, NIH, Bethesda, MD 20892 USA.
[Utsuki, Tadanobu] Louisiana State Univ, Sch Vet Med, Dept Pathobiol Sci, Skip Bertman Dr, Baton Rouge, LA 70803 USA.
[Shin, Taisun] Chonnam Natl Univ, Dept Food Sci & Nutr, Yeosu 550749, South Korea.
[Oh, Chul Woong] Pukyong Natl Univ, Dept Marine Biol, Busan 608737, South Korea.
[Lee, Bonggi] Pusan Natl Univ, Coll Pharm, Busan, South Korea.
RP Kim, HR (reprint author), Pukyong Natl Univ, Dept Food Sci & Nutr, Busan 608737, South Korea.
EM hrkim@pknu.ac.kr
NR 1
TC 0
Z9 0
U1 16
U2 26
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0308-8146
EI 1873-7072
J9 FOOD CHEM
JI Food Chem.
PD JUL 1
PY 2016
VL 202
BP 521
EP 521
DI 10.1016/j.foodchem.2016.02.084
PG 1
WC Chemistry, Applied; Food Science & Technology; Nutrition & Dietetics
SC Chemistry; Food Science & Technology; Nutrition & Dietetics
GA DE7IS
UT WOS:000370810000070
ER
PT J
AU Revell, A
Khabo, P
Ledwaba, L
Emery, S
Wang, D
Wood, R
Morrow, C
Tempelman, H
Hamers, RL
Reiss, P
van Sighem, A
Pozniak, A
Montaner, J
Lane, HC
Larder, B
AF Revell, Andrew
Khabo, Paul
Ledwaba, Lotty
Emery, Sean
Wang, Dechao
Wood, Robin
Morrow, Carl
Tempelman, Hugo
Hamers, Raph L.
Reiss, Peter
van Sighem, Ard
Pozniak, Anton
Montaner, Julio
Lane, H. Clifford
Larder, Brendan
TI Computational models as predictors of HIV treatment outcomes for the
Phidisa cohort in South Africa
SO SOUTHERN AFRICAN JOURNAL OF HIV MEDICINE
LA English
DT Article
ID RESOURCE-LIMITED SETTINGS; THERAPY; GENOTYPE
AB Background: Selecting the optimal combination of HIV drugs for an individual in resourcelimited settings is challenging because of the limited availability of drugs and genotyping.
Objective: The evaluation as a potential treatment support tool of computational models that predict response to therapy without a genotype, using cases from the Phidisa cohort in South Africa.
Methods: Cases from Phidisa of treatment change following failure were identified that had the following data available: baseline CD4 count and viral load, details of failing and previous antiretroviral drugs, drugs in new regimen and time to follow-up. The HIV Resistance Response Database Initiative's (RDI's) models used these data to predict the probability of a viral load < 50 copies/mL at follow-up. The models were also used to identify effective alternative combinations of three locally available drugs.
Results: The models achieved accuracy (area under the receiver-operator characteristic curve) of 0.72 when predicting response to therapy, which is less accurate than for an independent global test set (0.80) but at least comparable to that of genotyping with rules-based interpretation. The models were able to identify alternative locally available three-drug regimens that were predicted to be effective in 69% of all cases and 62% of those whose new treatment failed in the clinic.
Conclusion: The predictive accuracy of the models for these South African patients together with the results of previous studies suggest that the RDI's models have the potential to optimise treatment selection and reduce virological failure in different patient populations, without the use of a genotype.
C1 [Revell, Andrew; Wang, Dechao] HIV Resistance Response Database Initiat RDI, London, England.
[Khabo, Paul] SAMHS, Project PHIDISA, Lyttelton, South Africa.
[Ledwaba, Lotty; Reiss, Peter] SANDF, Project PHIDISA, Lyttelton, South Africa.
[Emery, Sean] Univ New South Wales, Kirby Inst, Sydney, NSW, Australia.
[Wood, Robin; Reiss, Peter] Univ Cape Town, Desmond Tutu HIV Ctr, Cape Town, South Africa.
[Tempelman, Hugo] Ndlovu Care Grp, Elandsdoorn, South Africa.
[Hamers, Raph L.] Univ Amsterdam, Acad Med Ctr, Amsterdam, Netherlands.
[Reiss, Peter] Stichting HIV Monitoring, Amsterdam, Netherlands.
[Pozniak, Anton] Chelsea & Westminster Hosp, London, England.
[Montaner, Julio] BC Ctr Excellence HIV AIDS, Vancouver, WA USA.
[Lane, H. Clifford] Nat Inst Allergy & Infect Dis, Bethesda, MD USA.
RP Revell, A (reprint author), HIV Resistance Response Database Initiat RDI, London, England.
EM andrewrevell@hivrdi.org
RI Emery, Sean/H-4920-2013
OI Emery, Sean/0000-0001-6072-8309
FU federal funds from the National Cancer Institute, National Institutes of
Health [HHSN261200800001E]; National Institute of Allergy and Infectious
Diseases
FX This project has been funded in whole or in part with federal funds from
the National Cancer Institute, National Institutes of Health, under
Contract No. HHSN261200800001E. This research was supported by the
National Institute of Allergy and Infectious Diseases. The content of
this publication does not necessarily reflect the views or policies of
the Department of Health and Human Services, nor does mention of trade
names, commercial products, or organisations imply endorsement by the
U.S. Government.
NR 16
TC 0
Z9 0
U1 0
U2 0
PU AOSIS
PI CAPE TOWN
PA POSTNET SUITE 55, PRIVATE BAG X22, TYGERVALLEY, CAPE TOWN, 00000, SOUTH
AFRICA
SN 1608-9693
EI 2078-6751
J9 S AFR J HIV MED
JI South. Afr. J. HIV Med.
PD JUN 30
PY 2016
VL 17
IS 1
AR UNSP 450
DI 10.4102/sajhivmed.v17i1.450
PG 7
WC Infectious Diseases; Virology
SC Infectious Diseases; Virology
GA EK0IW
UT WOS:000393611100001
ER
PT J
AU Sannerud, R
Esselens, C
Ejsmont, P
Mattera, R
Rochin, L
Tharkeshwar, AK
De Baets, G
De Wever, V
Habets, R
Baert, V
Vermeire, W
Michiels, C
Groot, AJ
Wouters, R
Dillen, K
Vints, K
Baatsen, P
Munck, S
Derua, R
Waelkens, E
Basi, GS
Mercken, M
Vooijs, M
Bollen, M
Schymkowitz, J
Rousseau, F
Bonifacino, JS
Van Niel, G
De Strooper, B
Annaert, W
AF Sannerud, Ragna
Esselens, Cary
Ejsmont, Paulina
Mattera, Rafael
Rochin, Leila
Tharkeshwar, Arun Kumar
De Baets, Greet
De Wever, Veerle
Habets, Roger
Baert, Veerle
Vermeire, Wendy
Michiels, Christine
Groot, Arjan J.
Wouters, Rosanne
Dillen, Katleen
Vints, Katlijn
Baatsen, Pieter
Munck, Sebastian
Derua, Rita
Waelkens, Etienne
Basi, Guriqbal S.
Mercken, Mark
Vooijs, Marc
Bollen, Mathieu
Schymkowitz, Joost
Rousseau, Frederic
Bonifacino, Juan S.
Van Niel, Guillaume
De Strooper, Bart
Annaert, Wim
TI Restricted Location of PSEN2/gamma-Secretase Determines Substrate
Specificity and Generates an Intracellular A beta Pool
SO CELL
LA English
DT Article
ID GAMMA-SECRETASE ACTIVITY; LYSOSOMAL MEMBRANE-PROTEINS;
ALZHEIMERS-DISEASE; ENDOSOMAL DYSFUNCTION; AMYLOID ACCUMULATION;
FORCE-FIELD; LOCALIZATION; PRESENILINS; MUTATIONS; MECHANISM
AB gamma-Secretases are a family of intramembrane-cleaving proteases involved in various signaling pathways and diseases, including Alzheimer's disease (AD). Cells co-express differing gamma-secretase complexes, including two homologous presenilins (PSENs). We examined the significance of this heterogeneity and identified a unique motif in PSEN2 that directs this gamma-secretase to late endosomes/lysosomes via a phosphorylation-dependent interaction with the AP-1 adaptor complex. Accordingly, PSEN2 selectively cleaves late endosomal/lysosomal localized substrates and generates the prominent pool of intracellular A beta that contains longer A beta; familial AD (FAD)-associated mutations in PSEN2 increased the levels of longer A beta further. Moreover, a subset of FAD mutants in PSEN1, normally more broadly distributed in the cell, phenocopies PSEN2 and shifts its localization to late endosomes/lysosomes. Thus, localization of gamma-secretases determines substrate specificity, while FAD-causing mutations strongly enhance accumulation of aggregation-prone A beta 42 in intracellular acidic compartments. The findings reveal potentially important roles for specific intracellular, localized reactions contributing to AD pathogenesis.
C1 [Sannerud, Ragna; Esselens, Cary; Ejsmont, Paulina; Tharkeshwar, Arun Kumar; Baert, Veerle; Vermeire, Wendy; Michiels, Christine; Wouters, Rosanne; Dillen, Katleen; De Strooper, Bart; Annaert, Wim] Katholieke Univ Leuven, VIB Ctr Biol Dis, B-3000 Leuven, Belgium.
[Sannerud, Ragna; Esselens, Cary; Ejsmont, Paulina; Tharkeshwar, Arun Kumar; Baert, Veerle; Vermeire, Wendy; Michiels, Christine; Wouters, Rosanne; Dillen, Katleen; De Strooper, Bart; Annaert, Wim] Katholieke Univ Leuven, Dept Human Genet, B-3000 Leuven, Belgium.
[Mattera, Rafael; Bonifacino, Juan S.] NICHD, Cell Biol & Neurobiol Branch, NIH, Bethesda, MD 20892 USA.
[Rochin, Leila; Van Niel, Guillaume] PSL Res Univ, CNRS, Inst Curie, UMR 144, F-75005 Paris, France.
[Rochin, Leila; Van Niel, Guillaume] CNRS, UMR 144, F-75005 Paris, France.
[De Baets, Greet; Schymkowitz, Joost; Rousseau, Frederic] Katholieke Univ Leuven, VIB Switch Lab, B-3000 Louvain, Belgium.
[De Baets, Greet; De Wever, Veerle; Derua, Rita; Waelkens, Etienne; Bollen, Mathieu; Schymkowitz, Joost; Rousseau, Frederic] Katholieke Univ Leuven, Dept Cellular & Mol Med, B-3000 Louvain, Belgium.
[Groot, Arjan J.; Vooijs, Marc] Maastricht Univ, Dept Radiotherapy MAASTRO GROW, NL-6211 Maastricht, Netherlands.
[Vints, Katlijn; Baatsen, Pieter; Munck, Sebastian] VIB BioImaging Core, B-3000 Louvain, Belgium.
[Basi, Guriqbal S.] Avalanche Biotechnol, Menlo Pk, CA 94025 USA.
[Mercken, Mark] Janssen Pharmaceut, B-2340 Beerse, Belgium.
[De Strooper, Bart] UCL Inst Neurol, Dept Mol Neurosci, London WC1E 6BT, England.
RP Annaert, W (reprint author), Katholieke Univ Leuven, VIB Ctr Biol Dis, B-3000 Leuven, Belgium.; Annaert, W (reprint author), Katholieke Univ Leuven, Dept Human Genet, B-3000 Leuven, Belgium.
EM wim.annaert@cme.vib-kuleuven.be
RI Rousseau, Frederic/J-9044-2016;
OI Rousseau, Frederic/0000-0002-9189-7399; Esselens,
Cary/0000-0001-8876-634X
FU VIB; KU Leuven [C16/15/073, IDO/12/020]; federal government [IAP P7/16];
Hercules [AKUL/09/037, 11/30, 13/39]; SAO [14017]; Alzheimer's
Association [IIRG-08-91535]; NICHD Intramural Program [ZIA HD001607];
IWT; EU-ERC [208259]; "Fondation ARC" [DOC20130606986, PJA20131200286]
FX Financial support was from VIB (W.A., B.D.S., F.R., and J.S.), KU Leuven
(C16/15/073 and IDO/12/020 to W.A.), the federal government (IAP P7/16:
W.A., B.D.S., F.R., and J.S.), Hercules (AKUL/09/037, 11/30, 13/39 to
W.A.), SAO (S#14017 to W.A.), the Alzheimer's Association (IIRG-08-91535
to W.A.), and the NICHD Intramural Program (ZIA HD001607 to J.S.B.).
A.K.T. and G.D.B. held PhD fellowships from VIB and IWT. We thank K.
Ivanova for initial FP-PSEN rescue. P.E. was a Marie-Curie postdoc, and
R.W. is an FWO fellow. A.G., R.H., and M.V. are supported by EU-ERC
(208259); L.R. and G.V.N. are supported by "Fondation ARC" (no.
DOC20130606986 and # PJA20131200286). We thank PICT-IBiSA (Institut
Curie) and France-Bio-Imaging (ANR-10-INSB-04).
NR 51
TC 10
Z9 10
U1 11
U2 13
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0092-8674
EI 1097-4172
J9 CELL
JI Cell
PD JUN 30
PY 2016
VL 166
IS 1
BP 193
EP 208
DI 10.1016/j.cell.2016.05.020
PG 16
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA DR9ZH
UT WOS:000380254400021
PM 27293189
ER
PT J
AU Khundakar, AA
Hanson, PS
Erskine, D
Lax, NZ
Roscamp, J
Karyka, E
Tsefou, E
Singh, P
Cockell, SJ
Gribben, A
Ramsay, L
Blain, PG
Mosimann, UP
Lett, DJ
Elstner, M
Turnbull, DM
Xiang, CC
Brownstein, MJ
O'Brien, JT
Taylor, JP
Attems, J
Thomas, AJ
McKeith, IG
Morris, CM
AF Khundakar, Ahmad A.
Hanson, Peter S.
Erskine, Daniel
Lax, Nichola Z.
Roscamp, Joseph
Karyka, Evangelia
Tsefou, Eliona
Singh, Preeti
Cockell, Simon J.
Gribben, Andrew
Ramsay, Lynne
Blain, Peter G.
Mosimann, Urs P.
Lett, Deborah J.
Elstner, Matthias
Turnbull, Douglass M.
Xiang, Charles C.
Brownstein, Michael J.
O'Brien, John T.
Taylor, John-Paul
Attems, Johannes
Thomas, Alan J.
McKeith, Ian G.
Morris, Christopher M.
TI Analysis of primary visual cortex in dementia with Lewy bodies indicates
GABAergic involvement associated with recurrent complex visual
hallucinations
SO ACTA NEUROPATHOLOGICA COMMUNICATIONS
LA English
DT Article
DE Dementia with Lewy bodies; alpha-synuclein; Primary visual cortex;
Hallucinations; Alzheimer's disease
ID TEMPORAL AREAS TE; PARKINSON-DISEASE DEMENTIA; ALZHEIMERS-DISEASE;
MACAQUE MONKEYS; SUBCORTICAL CONNECTIONS; DEPENDENT PLASTICITY; ILLUMINA
MICROARRAY; BODY DEMENTIAS; BRAIN; PATHOLOGY
AB Dementia with Lewy bodies (DLB) patients frequently experience well formed recurrent complex visual hallucinations (RCVH). This is associated with reduced blood flow or hypometabolism on imaging of the primary visual cortex. To understand these associations in DLB we used pathological and biochemical analysis of the primary visual cortex to identify changes that could underpin RCVH. Alpha-synuclein or neurofibrillary tangle pathology in primary visual cortex was essentially absent. Neurone density or volume within the primary visual cortex in DLB was also unchanged using unbiased stereology. Microarray analysis, however, demonstrated changes in neuropeptide gene expression and other markers, indicating altered GABAergic neuronal function. Calcium binding protein and GAD65/67 immunohistochemistry showed preserved interneurone populations indicating possible interneurone dysfunction. This was demonstrated by loss of post synaptic GABA receptor markers including gephyrin, GABARAP, and Kif5A, indicating reduced GABAergic synaptic activity. Glutamatergic neuronal signalling was also altered with vesicular glutamate transporter protein and PSD-95 expression being reduced. Changes to the primary visual cortex in DLB indicate that reduced GABAergic transmission may contribute to RCVH in DLB and treatment using targeted GABAergic modulation or similar approaches using glutamatergic modification may be beneficial.
C1 [Khundakar, Ahmad A.; Erskine, Daniel; Lax, Nichola Z.; Ramsay, Lynne; Lett, Deborah J.; Turnbull, Douglass M.; Attems, Johannes; Morris, Christopher M.] Newcastle Univ, Inst Neurosci, Edwardson Bldg,Campus Ageing & Vital,Westgate Rd, Newcastle Upon Tyne NE4 5PL, Tyne & Wear, England.
[Hanson, Peter S.; Erskine, Daniel; Roscamp, Joseph; Karyka, Evangelia; Tsefou, Eliona; Singh, Preeti; Gribben, Andrew; Blain, Peter G.; Morris, Christopher M.] Newcastle Univ, Med Toxicol Ctr, Wolfson Bldg,Claremont Pl, Newcastle Upon Tyne NE2 4AA, Tyne & Wear, England.
[Lax, Nichola Z.; Turnbull, Douglass M.] Newcastle Univ, Sch Med, Inst Neurosci, Wellcome Trust Ctr Mitochondrial Res, Framlington Pl, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England.
[Cockell, Simon J.] Newcastle Univ, Bioinformat Support Unit, Leech Bldg,Frarnlington Pl, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England.
[Mosimann, Urs P.] Univ Bern, Univ Hosp Old Age Psychiat, CH-3010 Bern, Switzerland.
[Elstner, Matthias] Tech Univ Munich, Acad Hosp Bogenhausen, Dept Neurol & Clin Neurophysiol, Munich, Germany.
[Xiang, Charles C.; Brownstein, Michael J.; Morris, Christopher M.] NHGRI, Genet Lab, NIMH, NIH, Bethesda, MD 20892 USA.
[O'Brien, John T.; Taylor, John-Paul; Thomas, Alan J.; McKeith, Ian G.] Newcastle Univ, Inst Neurosci, Biomed Res Bldg,Westgate Rd, Newcastle Upon Tyne NE4 5PL, Tyne & Wear, England.
[O'Brien, John T.] Univ Cambridge, Sch Clin Med, Dept Psychiat, Box 189 Level E4 Cambridge Biomed Campus, Cambridge CB2 0SP, England.
RP Morris, CM (reprint author), Newcastle Univ, Inst Neurosci, Edwardson Bldg,Campus Ageing & Vital,Westgate Rd, Newcastle Upon Tyne NE4 5PL, Tyne & Wear, England.; Morris, CM (reprint author), Newcastle Univ, Med Toxicol Ctr, Wolfson Bldg,Claremont Pl, Newcastle Upon Tyne NE2 4AA, Tyne & Wear, England.; Morris, CM (reprint author), NHGRI, Genet Lab, NIMH, NIH, Bethesda, MD 20892 USA.
EM c.m.morris@ncl.ac.uk
OI Cockell, Simon/0000-0002-6831-9806
FU Medical Research Council [G0400074, G0502157, G0900652, G1100540,
MR/L016354/1]; Wellcome Trust [096919]
NR 102
TC 2
Z9 2
U1 2
U2 3
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 2051-5960
J9 ACTA NEUROPATHOL COM
JI Acta Neuropathol. Commun.
PD JUN 30
PY 2016
VL 4
AR UNSP 66
DI 10.1186/s40478-016-0334-3
PG 18
WC Neurosciences
SC Neurosciences & Neurology
GA DQ9IL
UT WOS:000379523500001
PM 27357212
ER
PT J
AU Brudno, JN
Kochenderfer, JN
AF Brudno, Jennifer N.
Kochenderfer, James N.
TI Toxicities of chimeric antigen receptor T cells: recognition and
management
SO BLOOD
LA English
DT Review
ID CYTOKINE RELEASE SYNDROME; ANTITUMOR-ACTIVITY; PHASE-I;
RHEUMATOID-ARTHRITIS; ENGAGING THERAPIES; RETROVIRAL VECTOR;
RANDOMIZED-TRIAL; CLINICAL-TRIAL; ADVERSE EVENT; TUMOR-GROWTH
AB Chimeric antigen receptor (CAR) T cells can produce durable remissions in hematologic malignancies that are not responsive to standard therapies. Yet the use of CAR T cells is limited by potentially severe toxicities. Early case reports of unexpected organ damage and deaths following CAR T-cell therapy first highlighted the possible dangers of this new treatment. CAR T cells can potentially damage normal tissues by specifically targeting a tumor-associated antigen that is also expressed on those tissues. Cytokine release syndrome (CRS), a systemic inflammatory response caused by cytokines released by infused CAR T cells can lead to widespread reversible organ dysfunction. CRS is the most common type of toxicity caused by CAR T cells. Neurologic toxicity due to CAR T cells might in some cases have a different pathophysiology than CRS and requires different management. Aggressive supportive care is necessary for all patients experiencing CAR T-cell toxicities, with early intervention for hypotension and treatment of concurrent infections being essential. Interleukin-6 receptor blockade with tocilizumab remains the mainstay pharmacologic therapy for CRS, though indications for administration vary among centers. Corticosteroids should be reserved for neurologic toxicities and CRS not responsive to tocilizumab. Pharmacologic management is complicated by the risk of immunosuppressive therapy abrogating the antimalignancy activity of the CAR T cells. This review describes the toxicities caused by CAR T cells and reviews the published approaches used to manage toxicities. We present guidelines for treating patients experiencing CRS and other adverse events following CAR T-cell therapy.
C1 [Brudno, Jennifer N.] NCI, Off Clin Director, Ctr Canc Res, Bethesda, MD 20892 USA.
[Kochenderfer, James N.] NCI, Expt Transplantat & Immunol Branch, Bethesda, MD 20892 USA.
RP Kochenderfer, JN (reprint author), NIH Bldg 10,10 Ctr Dr,CRC Room 3-3888, Bethesda, MD 20892 USA.
EM kochendj@mail.nih.gov
FU NCI
FX Funding for preparation of this review was provided by the NCI
intramural funds.
NR 71
TC 22
Z9 23
U1 5
U2 9
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA
SN 0006-4971
EI 1528-0020
J9 BLOOD
JI Blood
PD JUN 30
PY 2016
VL 127
IS 26
BP 3321
EP 3330
DI 10.1182/blood-2016-04-703751
PG 10
WC Hematology
SC Hematology
GA DQ5MC
UT WOS:000379248500008
PM 27207799
ER
PT J
AU Gertz, EM
Chowdhury, SA
Lee, WJ
Wangsa, D
Heselmeyer-Haddad, K
Ried, T
Schwartz, R
Schaffer, AA
AF Gertz, E. Michael
Chowdhury, Salim Akhter
Lee, Woei-Jyh
Wangsa, Darawalee
Heselmeyer-Haddad, Kerstin
Ried, Thomas
Schwartz, Russell
Schaffer, Alejandro A.
TI FISHtrees 3.0: Tumor Phylogenetics Using a Ploidy Probe
SO PLOS ONE
LA English
DT Article
ID COPY NUMBER CHANGES; IN-SITU HYBRIDIZATION; CELL GENETIC-ANALYSIS;
CROSS-SECTIONAL DATA; CLONAL EVOLUTION; BREAST-CANCER; SEQUENCING DATA;
MAXIMUM-LIKELIHOOD; PROGRESSION MODELS; ONCOGENETIC TREE
AB Advances in fluorescence in situ hybridization (FISH) make it feasible to detectmultiple copy-number changes in hundreds of cells of solid tumors. Studies using FISH, sequencing, and other technologies have revealed substantial intra-tumor heterogeneity. The evolution of subclones in tumors may bemodeled by phylogenies. Tumors often harbor aneuploid or polyploid cell populations. Using a FISH probe to estimate changes in ploidy can guide the creation of trees that model changes in ploidy and individual gene copy-number variations. We present FISHtrees 3.0, which implements a ploidy-based tree building method based on mixed integer linear programming (MILP). The ploidy-based modeling in FISHtrees includes a new formulation of the problem of merging trees for changes of a single gene into trees modeling changes in multiple genes and the ploidy. When multiple samples are collected from each patient, varying over time or tumor regions, it is useful to evaluate similarities in tumor progression among the samples. Therefore, we further implemented in FISHtrees 3.0 a new method to build consensus graphs for multiple samples. We validate FISHtrees 3.0 on a simulated data and on FISH data from paired cases of cervical primary and metastatic tumors and on paired breast ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC). Tests on simulated data show improved accuracy of the ploidy-based approach relative to prior ploidyless methods. Tests on real data further demonstrate novel insights these methods offer into tumor progression processes. Trees for DCIS samples are significantly less complex than trees for paired IDC samples. Consensus graphs show substantial divergence among most paired samples from both sets. Low consensus between DCIS and IDC trees may help explain the difficulty in finding biomarkers that predict which DCIS cases are at most risk to progress to IDC. The FISHtrees software is available at ftp://ftp.ncbi.nih.gov/pub/FISHtrees.
C1 [Gertz, E. Michael] US Natl Inst Hlth, Natl Ctr Biotechnol Informat, Computat Biol Branch, 31 Ctr Dr, Bethesda, MD 20892 USA.
[Chowdhury, Salim Akhter; Schwartz, Russell] Carnegie Mellon Univ, Computat Biol Dept, Pittsburgh, PA USA.
[Chowdhury, Salim Akhter] Carnegie Mellon Univ Pittsburgh, Joint PhD Program Computat Biol, Pittsburgh, PA USA.
[Wangsa, Darawalee; Heselmeyer-Haddad, Kerstin; Ried, Thomas] US Natl Inst Hlth, Sect Canc Genom, Genet Branch, Ctr Canc Res,Natl Canc Inst, Bethesda, MD USA.
[Schwartz, Russell] Carnegie Mellon Univ, Dept Biol Sci, Pittsburgh, PA USA.
[Chowdhury, Salim Akhter] Simons Fdn, Simons Ctr Data Anal, New York, NY USA.
[Chowdhury, Salim Akhter] Princeton Univ, Lewis Sigler Inst Integrat Genom, Princeton, NJ USA.
[Lee, Woei-Jyh] Univ Maryland, Robert H Smith Sch Business, Dept Decis Operat & Informat Technol, College Pk, MD USA.
RP Gertz, EM (reprint author), US Natl Inst Hlth, Natl Ctr Biotechnol Informat, Computat Biol Branch, 31 Ctr Dr, Bethesda, MD 20892 USA.
EM gertz@ncbi.nlm.nih.gov
RI Schwartz, Russell/A-1998-2016
OI Schwartz, Russell/0000-0002-4970-2252
FU Intramural Research Program of the National Institutes of Health, NLM
and NCI; U.S. National Institutes of Health [1R01CA140214]
FX This work was supported in part by the Intramural Research Program of
the National Institutes of Health, NLM and NCI, and by U.S. National
Institutes of Health award 1R01CA140214. The funders had no role in
study design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 74
TC 1
Z9 1
U1 0
U2 2
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUN 30
PY 2016
VL 11
IS 6
AR e0158569
DI 10.1371/journal.pone.0158569
PG 27
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DQ0CH
UT WOS:000378865200093
PM 27362268
ER
PT J
AU Mitra, A
Herren, CD
Patel, IR
Coleman, A
Mukhopadhyay, S
AF Mitra, Arindam
Herren, Christopher D.
Patel, Isha R.
Coleman, Adam
Mukhopadhyay, Suman
TI Integration of AI-2 Based Cell-Cell Signaling with Metabolic Cues in
Escherichia coli
SO PLOS ONE
LA English
DT Article
ID VIRULENCE GENE-EXPRESSION; SALMONELLA-TYPHIMURIUM; RESPONSE REGULATOR;
BIOFILM FORMATION; VIBRIO-CHOLERAE; GLOBAL CONTROL; QUORUM; LUXS;
PSEUDOMONAS; SYSTEM
AB The quorum sensing molecule Autoinducer-2 (AI-2) is generated as a byproduct of activated methyl cycle by the action of LuxS in Escherichia coli. AI-2 is synthesized, released and later internalized in a cell-density dependent manner. Here, by mutational analysis of the genes, uvrY and csrA, we describe a regulatory circuit of accumulation and uptake of AI-2. We constructed a single-copy chromosomal luxS-lacZ fusion in a luxS (+) merodiploid strain and evaluated its relative expression in uvrY and csrA mutants. At the entry of stationary phase, the expression of the fusion and AI-2 accumulation was positively regulated by uvrY and negatively regulated by csrA respectively. A deletion of csrA altered message stability of the luxS transcript and CsrA protein exhibited weak binding to 5' luxS regulatory region. DNA protein interaction and chromatin immunoprecipitation analysis confirmed direct interaction of UvrY with the luxS promoter. Additionally, reduced expression of the fusion in hfq deletion mutant suggested involvement of small RNA interactions in luxS regulation. In contrast, the expression of lsrA operon involved in AI-2 uptake, is negatively regulated by uvrY and positively by csrA in a cell-density dependent manner. The dual role of csrA in AI-2 synthesis and uptake suggested a regulatory crosstalk of cell signaling with carbon regulation in Escherichia coli. We found that the cAMP-CRP mediated catabolite repression of luxS expression was uvrY dependent. This study suggests that luxS expression is complex and regulated at the level of transcription and translation. The multifactorial regulation supports the notion that cell-cell communication requires interaction and integration of multiple metabolic signals.
C1 [Mitra, Arindam; Herren, Christopher D.; Patel, Isha R.; Coleman, Adam; Mukhopadhyay, Suman] Univ Maryland, Virginia Maryland Reg Coll Vet Med, College Pk, MD 20742 USA.
[Mitra, Arindam] Adamas Univ, Dept Microbiol, Kolkata, W Bengal, India.
[Herren, Christopher D.] Kansas State Univ, Div Biol, Manhattan, KS USA.
[Patel, Isha R.] US FDA, Div Mol Biol, Off Appl Res & Safety Assessment HFS 025, Ctr Food Safety & Appl Nutr, Laurel, MD USA.
[Coleman, Adam] Maryland Dept Hlth & Mental Hyg, Div Newborn & Childhood Screening, Baltimore, MD USA.
[Mukhopadhyay, Suman] NIAID, Div Microbiol & Infect Dis, NIH, Bethesda, MD USA.
RP Mukhopadhyay, S (reprint author), Univ Maryland, Virginia Maryland Reg Coll Vet Med, College Pk, MD 20742 USA.; Mukhopadhyay, S (reprint author), NIAID, Div Microbiol & Infect Dis, NIH, Bethesda, MD USA.
EM mukhopadhyays@mail.nih.gov
FU USDA-NRI-CSREES Competitive Grant [2004-35204-14749]; USDA-Animal Health
[2002-1106-0195318]; Maryland Agriculture Experimental Station grant
from the University of Maryland
FX This work was in part supported by USDA-NRI-CSREES Competitive Grant
2004-35204-14749, USDA-Animal Health 2002-1106-0195318 and Maryland
Agriculture Experimental Station grant from the University of Maryland.
The funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 63
TC 0
Z9 0
U1 7
U2 10
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUN 30
PY 2016
VL 11
IS 6
AR e0157532
DI 10.1371/journal.pone.0157532
PG 19
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DQ0CH
UT WOS:000378865200019
PM 27362507
ER
PT J
AU Xu, ZZ
Proschan, M
Lee, S
AF Xu, Zhenzhen
Proschan, Michael
Lee, Shiowjen
TI Validity and power considerations on hypothesis testing under
minimization
SO STATISTICS IN MEDICINE
LA English
DT Article
DE covariate adaptive randomization; minimization; dynamic allocation;
randomization; analyze as you randomize; re-randomization test;
permutation test; temporal trend; validity; power
ID COVARIATE-ADAPTIVE RANDOMIZATION; TREATMENT ALLOCATION PROCEDURES;
BIASED COIN DESIGN; CLINICAL-TRIALS; PROGNOSTIC-FACTORS; BALANCE
AB Minimization, a dynamic allocation method, is gaining popularity especially in cancer clinical trials. Aiming to achieve balance on all important prognostic factors simultaneously, this procedure can lead to a substantial reduction in covariate imbalance compared with conventional randomization in small clinical trials. While minimization has generated enthusiasm, some controversy exists over the proper analysis of such a trial. Critics argue that standard testing methods that do not account for the dynamic allocation algorithm can lead to invalid statistical inference. Acknowledging this limitation, the International Conference on Harmonization E9 guideline suggests that 'the complexity of the logistics and potential impact on analyses be carefully evaluated when considering dynamic allocation'. In this article, we investigate the proper analysis approaches to inference in a minimization design for both continuous and time-to-event endpoints and evaluate the validity and power of these approaches under a variety of scenarios both theoretically and empirically. Published 2016. This article is a U.S. Government work and is in the public domain in the USA
C1 [Xu, Zhenzhen; Lee, Shiowjen] US FDA, CBER, Silver Spring, MD 20993 USA.
[Proschan, Michael] NIAID, Biostat Res Branch, 9000 Rockville Pike, Bethesda, MD 20892 USA.
RP Xu, ZZ (reprint author), US FDA, CBER, Silver Spring, MD 20993 USA.
EM Zhenzhen.Xu@fda.hhs.gov
NR 32
TC 2
Z9 2
U1 4
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0277-6715
EI 1097-0258
J9 STAT MED
JI Stat. Med.
PD JUN 30
PY 2016
VL 35
IS 14
BP 2315
EP 2327
DI 10.1002/sim.6874
PG 13
WC Mathematical & Computational Biology; Public, Environmental &
Occupational Health; Medical Informatics; Medicine, Research &
Experimental; Statistics & Probability
SC Mathematical & Computational Biology; Public, Environmental &
Occupational Health; Medical Informatics; Research & Experimental
Medicine; Mathematics
GA DP5LB
UT WOS:000378537100002
PM 26787557
ER
PT J
AU von der Ecken, J
Heissler, SM
Pathan-Chhatbar, S
Manstein, DJ
Raunser, S
AF von der Ecken, Julian
Heissler, Sarah M.
Pathan-Chhatbar, Salma
Manstein, Dietmar J.
Raunser, Stefan
TI Cryo-EM structure of a human cytoplasmic actomyosin complex at
near-atomic resolution
SO NATURE
LA English
DT Article
ID HEAVY-CHAIN GENE; FAMILIAL HYPERTROPHIC CARDIOMYOPATHY; DICTYOSTELIUM
MYOSIN-II; ACTIN-BINDING SITE; BETA-MYOSIN; FUNCTIONAL-CHARACTERIZATION;
DILATED CARDIOMYOPATHY; MUSCLE-CONTRACTION; MISSENSE MUTATION; ATPASE
ACTIVITY
AB The interaction of myosin with actin filaments is the central feature of muscle contraction(1) and cargo movement along actin filaments of the cytoskeleton(2). The energy for these movements is generated during a complex mechanochemical reaction cycle(3,4). Crystal structures of myosin in different states have provided important structural insights into the myosin motor cycle when myosin is detached from F-actin(5-7). The difficulty of obtaining diffracting crystals, however, has prevented structure determination by crystallography of actomyosin complexes. Thus, although structural models exist of F-actin in complex with various myosins(8-11), a high-resolution structure of the F-actin-myosin complex is missing. Here, using electron cryomicroscopy, we present the structure of a human rigor actomyosin complex at an average resolution of 3.9 angstrom. The structure reveals details of the actomyosin interface, which is mainly stabilized by hydrophobic interactions. The negatively charged amino (N) terminus of actin interacts with a conserved basic motif in loop 2 of myosin, promoting cleft closure in myosin. Surprisingly, the overall structure of myosin is similar to rigor-like myosin structures in the absence of F-actin, indicating that F-actin binding induces only minimal conformational changes in myosin. A comparison with pre-powerstroke and intermediate (P-i-release)(7) states of myosin allows us to discuss the general mechanism of myosin binding to F-actin. Our results serve as a strong foundation for the molecular understanding of cytoskeletal diseases, such as autosomal dominant hearing loss and diseases affecting skeletal and cardiac muscles, in particular nemaline myopathy and hypertrophic cardiomyopathy.
C1 [von der Ecken, Julian; Raunser, Stefan] Max Planck Inst Mol Physiol, Dept Struct Biochem, D-44227 Dortmund, Germany.
[Heissler, Sarah M.; Pathan-Chhatbar, Salma; Manstein, Dietmar J.] Hannover Med Sch, Inst Biophys Chem, D-30625 Hannover, Germany.
[Manstein, Dietmar J.] Hannover Med Sch, Div Struct Anal, D-30625 Hannover, Germany.
[Heissler, Sarah M.] NHLBI, Lab Mol Physiol, NIH, Bldg 10, Bethesda, MD 20892 USA.
RP Raunser, S (reprint author), Max Planck Inst Mol Physiol, Dept Struct Biochem, D-44227 Dortmund, Germany.
EM stefan.raunser@mpi-dortmund.mpg.de
OI Raunser, Stefan/0000-0001-9373-3016
FU Max Planck Society; European Research Council under the European Union
[615984]; Behrens-Weise foundation; German Research Foundation (DFG) [MA
1081/21-1]
FX We thank O. Hofnagel for assistance in cryo sample preparation. We
acknowledge R. Matadeen and S. de Carlo for image acquisition at the
Netherlands Centre for Nanoscopy in Leiden. We thank R. S. Goody for
reading the manuscript. This work was supported by the Max Planck
Society, the European Research Council under the European Union's
Seventh Framework Program (FP7/2007-2013) (grant number 615984) (to
S.R.), the Behrens-Weise foundation (to S. R.) and German Research
Foundation (DFG) grant MA 1081/21-1 (to D.J.M.). J.v.d.E. is a fellow of
Studienstiftung des deutschen Volkes.
NR 78
TC 8
Z9 8
U1 11
U2 24
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 30
PY 2016
VL 534
IS 7609
BP 724
EP +
DI 10.1038/nature18295
PG 19
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DP7JV
UT WOS:000378676000045
PM 27324845
ER
PT J
AU Nghiem, PT
Bhatia, S
Lipson, EJ
Kudchadkar, RR
Miller, NJ
Annamalai, L
Berry, S
Chartash, EK
Daud, A
Fling, SP
Friedlander, PA
Kluger, HM
Kohrt, HE
Lundgren, L
Margolin, K
Mitchell, A
Olencki, T
Pardoll, DM
Reddy, SA
Shantha, EM
Sharfman, WH
Sharon, E
Shemanski, LR
Shinohara, MM
Sunshine, JC
Taube, JM
Thompson, JA
Townson, SM
Yearley, JH
Topalian, SL
Cheever, MA
AF Nghiem, Paul T.
Bhatia, Shailender
Lipson, Evan J.
Kudchadkar, Ragini R.
Miller, Natalie J.
Annamalai, Lakshmanan
Berry, Sneha
Chartash, Elliot K.
Daud, Adil
Fling, Steven P.
Friedlander, Philip A.
Kluger, Harriet M.
Kohrt, Holbrook E.
Lundgren, Lisa
Margolin, Kim
Mitchell, Alan
Olencki, Thomas
Pardoll, Drew M.
Reddy, Sunil A.
Shantha, Erica M.
Sharfman, William H.
Sharon, Elad
Shemanski, Lynn R.
Shinohara, Michi M.
Sunshine, Joel C.
Taube, Janis M.
Thompson, John A.
Townson, Steven M.
Yearley, Jennifer H.
Topalian, Suzanne L.
Cheever, Martin A.
TI PD-1 Blockade with Pembrolizumab in Advanced Merkel-Cell Carcinoma
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID LUNG-CANCER; IMMUNE RESISTANCE; POLYOMAVIRUS; RESPONSES; NIVOLUMAB;
EXPRESSION; SURVIVAL; TUMORS; CHEMOTHERAPY; ANTI-PD-1
AB BACKGROUND
Merkel-cell carcinoma is an aggressive skin cancer that is linked to exposure to ultraviolet light and the Merkel-cell polyomavirus (MCPyV). Advanced Merkel-cell carcinoma often responds to chemotherapy, but responses are transient. Blocking the programmed death 1 (PD-1) immune inhibitory pathway is of interest, because these tumors often express PD-L1, and MCPyV-specific T cells express PD-1.
METHODS
In this multicenter, phase 2, noncontrolled study, we assigned adults with advanced Merkel-cell carcinoma who had received no previous systemic therapy to receive pembrolizumab (anti-PD-1) at a dose of 2 mg per kilogram of body weight every 3 weeks. The primary end point was the objective response rate according to Response Evaluation Criteria in Solid Tumors, version 1.1. Efficacy was correlated with tumor viral status, as assessed by serologic and immunohistochemical testing.
RESULTS
A total of 26 patients received at least one dose of pembrolizumab. The objective response rate among the 25 patients with at least one evaluation during treatment was 56% (95% confidence interval [CI], 35 to 76); 4 patients had a complete response, and 10 had a partial response. With a median follow-up of 33 weeks (range, 7 to 53), relapses occurred in 2 of the 14 patients who had had a response (14%). The response duration ranged from at least 2.2 months to at least 9.7 months. The rate of progression-free survival at 6 months was 67% (95% CI, 49 to 86). A total of 17 of the 26 patients (65%) had virus-positive tumors. The response rate was 62% among patients with MCPyV-positive tumors (10 of 16 patients) and 44% among those with virus-negative tumors (4 of 9 patients). Drug-related grade 3 or 4 adverse events occurred in 15% of the patients.
CONCLUSIONS
In this study, first-line therapy with pembrolizumab in patients with advanced Merkel-cell carcinoma was associated with an objective response rate of 56%. Responses were observed in patients with virus-positive tumors and those with virus-negative tumors.
C1 [Nghiem, Paul T.; Bhatia, Shailender; Miller, Natalie J.; Shantha, Erica M.; Shinohara, Michi M.; Thompson, John A.; Cheever, Martin A.] Univ Washington, Med Ctr, 850 Republican St,Brotman Rm 240, Seattle, WA 98109 USA.
[Nghiem, Paul T.; Bhatia, Shailender; Fling, Steven P.; Lundgren, Lisa; Thompson, John A.; Cheever, Martin A.] Univ Washington, Fred Hutchinson Canc Res Ctr, 850 Republican St,Brotman Rm 240, Seattle, WA 98109 USA.
[Fling, Steven P.; Lundgren, Lisa; Cheever, Martin A.] Univ Washington, Canc Immunotherapy Trials Network, 850 Republican St,Brotman Rm 240, Seattle, WA 98109 USA.
[Mitchell, Alan; Shemanski, Lynn R.] Univ Washington, Canc Res & BioStat, 850 Republican St,Brotman Rm 240, Seattle, WA 98109 USA.
[Lipson, Evan J.; Berry, Sneha; Pardoll, Drew M.; Sharfman, William H.; Sunshine, Joel C.; Taube, Janis M.; Topalian, Suzanne L.] Johns Hopkins Univ, Sch Med, 1550 Orleans St,CBR2,Rm 508, Baltimore, MD 21287 USA.
[Lipson, Evan J.; Berry, Sneha; Pardoll, Drew M.; Sharfman, William H.; Sunshine, Joel C.; Taube, Janis M.; Topalian, Suzanne L.] Johns Hopkins Univ, Kimmel Canc Ctr, 1550 Orleans St,CBR2,Rm 508, Baltimore, MD 21287 USA.
[Sharon, Elad] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA.
[Kudchadkar, Ragini R.] Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA.
[Annamalai, Lakshmanan; Chartash, Elliot K.; Townson, Steven M.; Yearley, Jennifer H.] Merck Res Labs, Kenilworth, NJ USA.
[Daud, Adil] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Kohrt, Holbrook E.; Margolin, Kim; Reddy, Sunil A.] Stanford Univ, Stanford, CA 94305 USA.
[Friedlander, Philip A.] Mt Sinai Med Ctr, New York, NY 10029 USA.
[Kluger, Harriet M.] Yale Univ, New Haven, CT USA.
[Olencki, Thomas] Ohio State Univ, Columbus, OH 43210 USA.
RP Topalian, SL (reprint author), Johns Hopkins Univ, Sch Med, 1550 Orleans St,CBR2,Rm 508, Baltimore, MD 21287 USA.; Nghiem, PT (reprint author), Univ Washington, Dermatol Med, 850 Republican St,Brotman Rm 240, Seattle, WA 98109 USA.
EM pnghiem@uw.edu; stopali1@jhmi.edu
RI Nghiem, Paul/A-9210-2011
OI Nghiem, Paul/0000-0003-2784-963X
FU National Cancer Institute; Merck
FX Funded by the National Cancer Institute and Merck; ClinicalTrials.gov
number, NCT02267603.
NR 40
TC 50
Z9 50
U1 7
U2 16
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
EI 1533-4406
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD JUN 30
PY 2016
VL 374
IS 26
BP 2542
EP 2552
DI 10.1056/NEJMoa1603702
PG 11
WC Medicine, General & Internal
SC General & Internal Medicine
GA DP8DD
UT WOS:000378727200006
PM 27093365
ER
PT J
AU Taurog, JD
Chhabra, A
Colbert, RA
AF Taurog, Joel D.
Chhabra, Avneesh
Colbert, Robert A.
TI Ankylosing Spondylitis and Axial Spondyloarthritis
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Review
ID SOCIETY CLASSIFICATION CRITERIA; ENTHESITIS-RELATED ARTHRITIS;
INFLAMMATORY BACK-PAIN; PERIPHERAL SPONDYLOARTHRITIS; JUVENILE
SPONDYLOARTHRITIS; SACROILIAC JOINTS; AMERICAN-COLLEGE; T-CELLS;
DISEASE; HLA-B27
C1 [Taurog, Joel D.] Univ Texas SW Med Ctr Dallas, Dept Internal Med, Div Rheumat Dis, 5323 Harry Hines Blvd, Dallas, TX 75390 USA.
[Chhabra, Avneesh] Univ Texas SW Med Ctr Dallas, Dept Radiol, Musculoskeletal Imaging Div, 5323 Harry Hines Blvd, Dallas, TX 75390 USA.
[Colbert, Robert A.] NIAMSD, Pediat Translat Res Branch, NIH, Bethesda, MD 20892 USA.
RP Taurog, JD (reprint author), Univ Texas SW Med Ctr Dallas, Dept Internal Med, Div Rheumat Dis, 5323 Harry Hines Blvd, Dallas, TX 75390 USA.
EM joel.taurog@utsouthwestern.edu
FU UT Southwestern; AbbVie Pharmaceuticals; Siemens; General
Electric-Association of University Radiologists
FX Dr. Taurog reports receiving laboratory funding and discretionary
funding through a license agreement between UT Southwestern and AbbVie
Pharmaceuticals, through which AbbVie has acquired access to HLA-B27
transgenic rats from Dr. Taurog's laboratory; Dr. Chhabra, receiving
fees for the development of computer-aided detection technology from
Siemens and grant support from the General Electric-Association of
University Radiologists; and Dr. Colbert, being principal investigator
in a cooperative research and development agreement between his
institution and Eli Lilly. No other potential conflict of interest
relevant to this article was reported.
NR 76
TC 16
Z9 16
U1 7
U2 12
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
EI 1533-4406
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD JUN 30
PY 2016
VL 374
IS 26
BP 2563
EP 2574
DI 10.1056/NEJMra1406182
PG 12
WC Medicine, General & Internal
SC General & Internal Medicine
GA DP8DD
UT WOS:000378727200008
PM 27355535
ER
PT J
AU Alam, MA
Arora, K
Gurrapu, S
Jonnalagadda, SK
Nelson, GL
Kiprof, P
Jonnalagadda, SC
Mereddy, VR
AF Alam, Mohammad A.
Arora, Kriti
Gurrapu, Shirisha
Jonnalagadda, Sravan K.
Nelson, Grady L.
Kiprof, Paul
Jonnalagadda, Subash C.
Mereddy, Venkatram R.
TI Synthesis and evaluation of functionalized benzoboroxoles as potential
anti-tuberculosis agents
SO TETRAHEDRON
LA English
DT Article
DE Benzoboroxoles; Nitrobenzoboroxole; Aminobenzoboroxole;
Bromoaminobenzoboroxole; anti-Tuberculosis agents
ID ALPHA-AMINO-ACIDS; MYCOBACTERIUM-TUBERCULOSIS; BENZOXABOROLES;
DISCOVERY; METHODOLOGIES; INHIBITORS; CHEMISTRY; SMEGMATIS; STRATEGY;
ANALOGS
AB Several derivatives of aminobenzoboroxole have been prepared starting from 2-boronobenzaldehyde. All of these derivatives have been evaluated for their anti-mycobacterial activity on Mycobacterium smegmatis and cytotoxicity on breast cancer cell line MCF7. Based on these studies, all the tested molecules have been found to be generally non-toxic and benzoboroxoles with unsubstituted (primary) amines have been found to exhibit good anti-mycobacterial activity. Some of the key compounds have been evaluated for their anti-tubercular activity on Mycobacterium tuberculosis H37Rv using 7H9 and GAST media. 7-Bromo-6-aminobenzoboroxole 4 has been identified as the lead candidate compound for further development. (C) 2016 Elsevier Ltd. All rights reserved.
C1 [Alam, Mohammad A.; Jonnalagadda, Subash C.] Rowan Univ, Dept Chem & Biochem, Glassboro, NJ 08028 USA.
[Arora, Kriti] NIAID, TB Res Sect, Lab Clin Infect Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Gurrapu, Shirisha; Jonnalagadda, Sravan K.; Nelson, Grady L.; Mereddy, Venkatram R.] Univ Minnesota, Integrated Biosci Grad Program, Duluth, MN 55812 USA.
[Kiprof, Paul; Mereddy, Venkatram R.] Univ Minnesota, Dept Chem & Biochem, Duluth, MN 55812 USA.
[Jonnalagadda, Subash C.] Rowan Univ, Dept Biomed & Translat Sci, Glassboro, NJ 08028 USA.
[Mereddy, Venkatram R.] Univ Minnesota, Dept Pharm Practice & Pharmaceut Sci, Duluth, MN 55812 USA.
RP Jonnalagadda, SC (reprint author), Rowan Univ, Dept Chem & Biochem, Glassboro, NJ 08028 USA.; Mereddy, VR (reprint author), Univ Minnesota, Integrated Biosci Grad Program, Duluth, MN 55812 USA.; Mereddy, VR (reprint author), Univ Minnesota, Dept Chem & Biochem, Duluth, MN 55812 USA.; Jonnalagadda, SC (reprint author), Rowan Univ, Dept Biomed & Translat Sci, Glassboro, NJ 08028 USA.; Mereddy, VR (reprint author), Univ Minnesota, Dept Pharm Practice & Pharmaceut Sci, Duluth, MN 55812 USA.
EM jonnalagadda@rowan.edu; vmereddy@d.umn.edu
OI Jonnalagadda, Subash/0000-0001-5234-1235
FU Intramural Research Program at NIAID, National Institutes of Health
FX The work was funded, in part by the Intramural Research Program at
NIAID, National Institutes of Health. We thank Dr. Clifton E. Barry and
Dr. Helena Boshoff (NIAID, NIH) for their guidance with the study. We
thank Dr. John Dahl, Department of Biology, University of Minnesota
Duluth for kindly providing Mycobacterium smegmatis culture. We thank
the Departments of Chemistry and Biochemistry at Rowan University and
University of Minnesota Duluth as well as the Integrated Biosciences
Program.
NR 66
TC 1
Z9 1
U1 7
U2 9
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0040-4020
J9 TETRAHEDRON
JI Tetrahedron
PD JUN 30
PY 2016
VL 72
IS 26
BP 3795
EP 3801
DI 10.1016/j.tet.2016.03.038
PG 7
WC Chemistry, Organic
SC Chemistry
GA DO4BB
UT WOS:000377725700024
PM 27642196
ER
PT J
AU Keil, MF
Briassoulis, G
Stratakis, CA
Wu, TJ
AF Keil, Margaret F.
Briassoulis, George
Stratakis, Constantine A.
Wu, T. John
TI Protein Kinase A and Anxiety-Related Behaviors: A Mini-Review
SO FRONTIERS IN ENDOCRINOLOGY
LA English
DT Review
DE protein kinase A; anxiety; knockout mice; regulatory subunit; catalytic
subunit
ID LONG-TERM POTENTIATION; OBSESSIVE-COMPULSIVE DISORDER; BASOLATERAL
AMYGDALA; PREFRONTAL CORTEX; MEMORY CONSOLIDATION; ANATOMICAL LOCATION;
KINDLING ELECTRODE; UNTREATED PATIENTS; MAJOR DEPRESSION; BIPOLAR
DISORDER
AB This review focuses on the anxiety related to cyclic AMP/protein kinase A (PKA) signaling pathway that regulates stress responses. PKA regulates an array of diverse signals that interact with various neurotransmitter systems associated with alertness, mood, and acute and social anxiety-like states. Recent mouse studies support the involvement of the PKA pathway in common neuropsychiatric disorders characterized by heightened activation of the amygdala. The amygdala is critical for adaptive responses leading to fear learning and aberrant fear memory and its heightened activation is widely thought to underpin various anxiety disorders. Stress-induced plasticity within the amygdala is involved in the transition from normal vigilance responses to emotional reactivity, fear over-generalization, and deficits in fear inhibition resulting in pathological anxiety and conditions, such as panic and depression. Human studies of PKA signaling defects also report an increased incidence of psychiatric disorders, including anxiety, depression, bipolar disorder, learning disorders, and attention deficit hyperactivity disorder. We speculate that the PKA system is uniquely suited for selective, molecularly targeted intervention that may be proven effective in anxiolytic therapy.
C1 [Keil, Margaret F.; Briassoulis, George; Stratakis, Constantine A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Endocrinol & Genet, NIH, Bethesda, MD 20892 USA.
[Briassoulis, George] Univ Crete, Dept Pediat Intens Care, Iraklion, Greece.
[Wu, T. John] Uniformed Serv Univ Hlth Sci, Dept Obstet & Gynecol, Ctr Neurosci & Regenerat Med, Bethesda, MD 20814 USA.
RP Keil, MF (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Endocrinol & Genet, NIH, Bethesda, MD 20892 USA.; Wu, TJ (reprint author), Uniformed Serv Univ Hlth Sci, Dept Obstet & Gynecol, Ctr Neurosci & Regenerat Med, Bethesda, MD 20814 USA.
EM keilm@mail.nih.gov; twu@usuhs.edu
FU NICHD, NIH [Z01-HD-000642-04]; Uniformed Services University of the
Health Sciences; Office of Naval Research; Department of Pediatrics,
Faculty of Medicine, University of Crete, Heraklion, Crete, Greece
FX The authors thank Dr. D. Omar Larco for critically reading this review.
This work was supported by NICHD, NIH intramural project
Z01-HD-000642-04 (CS). This study was supported in part by intramural
graduate student grant from the Uniformed Services University of the
Health Sciences (MK) and Office of Naval Research (TW) and, in part, by
the Department of Pediatrics, Faculty of Medicine, University of Crete,
Heraklion, Crete, Greece (GB).
NR 98
TC 2
Z9 2
U1 4
U2 4
PU FRONTIERS MEDIA SA
PI LAUSANNE
PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015,
SWITZERLAND
SN 1664-2392
J9 FRONT ENDOCRINOL
JI Front. Endocrinol.
PD JUN 29
PY 2016
VL 7
AR 83
DI 10.3389/fendo.2016.00083
PG 8
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA DY7DT
UT WOS:000385290500003
PM 27445986
ER
PT J
AU Panasevich, S
Haberg, SE
Aamodt, G
London, SJ
Stigum, H
Nystad, W
Nafstad, P
AF Panasevich, Sviatlana
Haberg, Siri Eldevik
Aamodt, Geir
London, Stephanie J.
Stigum, Hein
Nystad, Wenche
Nafstad, Per
TI Association between pregnancy exposure to air pollution and birth weight
in selected areas of Norway
SO ARCHIVES OF PUBLIC HEALTH
LA English
DT Article
DE Air pollution; Birth weight; MoBa; The Norwegian Mother and Child Cohort
Study
ID EPIDEMIOLOGIC EVIDENCE; PRETERM BIRTH; OUTCOMES; COHORT; HEALTH; RISK
AB Background: Exposure to air pollution has adverse effects on cardiopulmonary health of adults. Exposure to air pollution in pregnancy may affect foetal development. However, the evidence of such effect remains inconsistent. We investigated the effects of exposure to air pollution during pregnancy on birth outcomes.
Methods: This study, based within the Norwegian Mother and Child Cohort Study (MoBa), includes 17,533 participants living in the two largest cities in Norway: Oslo and Bergen, and their two surrounding counties: Akershus and Hordaland. Air pollution levels at residential addresses were estimated using land use regression models and back-extrapolated to the period of each pregnancy using continuous monitoring station data. Birth outcomes were birth weight, low birth weight, gestational age, and preterm delivery obtained from the Medical Birth Registry of Norway. Information on lifestyle factors was collected from MoBa questionnaires completed by mothers during pregnancy. Linear and logistic regression models were used to analyse the associations between pregnancy NO2 exposure and birth outcomes.
Results: We found a statistically significant negative association between pregnancy exposure to NO2 and birth weight -43.6 (95% CI -55.8 to -31.5) g per 10 mu g/m(3) NO2. However, after adjusting for either area or the combination of parity and maternal weight, no substantive effects of air pollution exposure were evident.
Conclusions: Exposure to air pollution during pregnancy was associated with decrease in birth weight, but area-related and lifestyle factors attenuated this association. We found no statistically significant associations of air pollution exposure with gestational age, low birth weight or preterm delivery.
C1 [Panasevich, Sviatlana; Haberg, Siri Eldevik; Stigum, Hein; Nystad, Wenche; Nafstad, Per] Norwegian Inst Publ Hlth, Domain Mental & Phys Hlth, Oslo, Norway.
[Aamodt, Geir] Norwegian Univ Life Sci, Dept Landscape Architecture & Spatial Plan, As, Norway.
[London, Stephanie J.] NIEHS, NIH, US Dept HHS, POB 12233, Res Triangle Pk, NC 27709 USA.
[Stigum, Hein; Nafstad, Per] Univ Oslo, Fac Med, Dept Gen Practice & Community Med, Oslo, Norway.
RP Panasevich, S (reprint author), Norwegian Inst Publ Hlth, Domain Mental & Phys Hlth, Oslo, Norway.
EM Sviatlana.Panasevich@fhi.no
OI London, Stephanie/0000-0003-4911-5290
FU NIEHS NIH HHS [N01ES75558, Z01 ES049019]; NINDS NIH HHS [U01 NS047537]
NR 22
TC 1
Z9 2
U1 2
U2 2
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 0778-7367
EI 2049-3258
J9 ARCH PUBLIC HEALTH
JI Arch. Public Health
PD JUN 29
PY 2016
VL 74
AR 26
DI 10.1186/s13690-016-0138-8
PG 9
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA DS0ZC
UT WOS:000380324400001
PM 27358731
ER
PT J
AU Opendak, M
Offit, L
Monari, P
Schoenfeld, TJ
Sonti, AN
Cameron, HA
Gould, E
AF Opendak, Maya
Offit, Lily
Monari, Patrick
Schoenfeld, Timothy J.
Sonti, Anup N.
Cameron, Heather A.
Gould, Elizabeth
TI Lasting Adaptations in Social Behavior Produced by Social Disruption and
Inhibition of Adult Neurogenesis
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
DE dominance hierarchy; GFAP-TK transgenic rats; hippocampus; neurogenesis;
oxytocin; social behavior
ID ELEVATED PLUS-MAZE; POSTTRAUMATIC-STRESS-DISORDER; BORN
HIPPOCAMPAL-NEURONS; NEURAL STEM-CELLS; DENTATE GYRUS; VICARIOUS TRIAL;
MALE-RATS; INSTABILITY STRESS; DECISION-MAKING; ERROR BEHAVIOR
AB Research on social instability has focused on its detrimental consequences, but most people are resilient and respond by invoking various coping strategies. To investigate cellular processes underlying such strategies, a dominance hierarchy of rats was formed and then destabilized. Regardless of social position, rats from disrupted hierarchies had fewer new neurons in the hippocampus compared with rats from control cages and those from stable hierarchies. Social disruption produced a preference for familiar over novel conspecifics, a change that did not involve global memory impairments or increased anxiety. Using the neuropeptide oxytocin as a tool to increase neurogenesis in the hippocampus of disrupted rats restored preference for novel conspecifics to predisruption levels. Conversely, reducing the number of new neurons by limited inhibition of adult neurogenesis in naive transgenic GFAP-thymidine kinase rats resulted in social behavior similar to disrupted rats. Together, these results provide novel mechanistic evidence that social disruption shapes behavior in a potentially adaptive way, possibly by reducing adult neurogenesis in the hippocampus.
C1 [Opendak, Maya; Offit, Lily; Monari, Patrick; Gould, Elizabeth] Princeton Univ, Princeton Neurosci Inst, Princeton, NJ 08540 USA.
[Offit, Lily; Monari, Patrick; Gould, Elizabeth] Princeton Univ, Dept Psychol, Princeton, NJ 08540 USA.
[Schoenfeld, Timothy J.; Sonti, Anup N.; Cameron, Heather A.] NIMH, NIH, Bethesda, MD 20892 USA.
[Opendak, Maya] Nathan S Kline Inst Psychiat Res, Emot Brain Inst, Orangeburg, NY USA.
[Opendak, Maya] NYU, Sch Med, Ctr Child Study, Child & Adolescent Psychiat, New York, NY USA.
RP Gould, E (reprint author), Princeton Univ, Princeton Neurosci Inst, Dept Psychol, Princeton, NJ 08540 USA.
EM goulde@princeton.edu
RI Cameron, Heather/E-6221-2011;
OI Cameron, Heather/0000-0002-3245-5777; Opendak, Maya/0000-0003-4334-3188
FU Intramural Program of the National Institutes of Health/National
Institute of Mental Health [ZIAMH002784]
FX This work was supported in part by the Intramural Program of the
National Institutes of Health/National Institute of Mental Health (Grant
ZIAMH002784 to H.A.C.).
NR 96
TC 2
Z9 2
U1 0
U2 2
PU SOC NEUROSCIENCE
PI WASHINGTON
PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA
SN 0270-6474
J9 J NEUROSCI
JI J. Neurosci.
PD JUN 29
PY 2016
VL 36
IS 26
BP 7027
EP 7038
DI 10.1523/JNEUROSCI.4435-15.2016
PG 12
WC Neurosciences
SC Neurosciences & Neurology
GA DQ2GJ
UT WOS:000379020200017
PM 27358459
ER
PT J
AU Kunimatsu, J
Suzuki, TW
Tanaka, M
AF Kunimatsu, Jun
Suzuki, Tomoki W.
Tanaka, Masaki
TI Implications of Lateral Cerebellum in Proactive Control of Saccades
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
DE anti-saccade; cerebellum; dentate nucleus; inactivation; primate; single
neurons
ID SUPPLEMENTARY EYE FIELD; PRIMATE GLOBUS-PALLIDUS; NEURONAL-ACTIVITY;
DENTATE NUCLEUS; BASAL GANGLIA; TRANSNEURONAL TRANSPORT; SUPERIOR
COLLICULUS; COGNITIVE CONTROL; MOTOR; MOVEMENTS
AB Although several lines of evidence establish the involvement of the medial and vestibular parts of the cerebellum in the adaptive control of eye movements, the role of the lateral hemisphere of the cerebellum in eye movements remains unclear. Ascending projections from the lateral cerebellum to the frontal and parietal association cortices via the thalamus are consistent with a role of these pathways in higher-order oculomotor control. In support of this, previous functional imaging studies and recent analyses in subjects with cerebellar lesions have indicated a role for the lateral cerebellum in volitional eye movements such as anti-saccades. To elucidate the underlying mechanisms, we recorded from single neurons in the dentate nucleus of the cerebellum in monkeys performing anti-saccade/pro-saccade tasks. We found that neurons in the posterior part of the dentate nucleus showed higher firing rates during the preparation of anti-saccades compared with pro-saccades. When the animals made erroneous saccades to the visual stimuli in the anti-saccade trials, the firing rate during the preparatory period decreased. Furthermore, local inactivation of the recording sites with muscimol moderately increased the proportion of error trials, while successful anti-saccades were more variable and often had shorter latency during inactivation. Thus, our results show that neuronal activity in the cerebellar dentate nucleus causally regulates anti-saccade performance. Neuronal signals from the lateral cerebellum to the frontal cortex might modulate the proactive control signals in the corticobasal ganglia circuitry that inhibit early reactive responses and possibly optimize the speed and accuracy of anti-saccades.
C1 [Kunimatsu, Jun; Suzuki, Tomoki W.; Tanaka, Masaki] Hokkaido Univ, Sch Med, Dept Physiol, North 15,West 7, Sapporo, Hokkaido 0608638, Japan.
[Kunimatsu, Jun] NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA.
RP Kunimatsu, J; Tanaka, M (reprint author), Hokkaido Univ, Sch Med, Dept Physiol, North 15,West 7, Sapporo, Hokkaido 0608638, Japan.
EM kunimatsu.jun@gmail.com; masaki@med.hokudai.ac.jp
RI Tanaka, Masaki/D-9199-2011
FU Ministry of Education, Culture, Sports, Science and Technology of Japan;
Ministry of Health, Labour and Welfare of Japan; Takeda Science
Foundation
FX This work was supported by grants from the Ministry of Education,
Culture, Sports, Science and Technology of Japan; the Ministry of
Health, Labour and Welfare of Japan; and the Takeda Science Foundation.
We thank R. Takeya for participating in some recording experiments; T.
Mori and A. Hironaka for their assistance with animal care, surgery, and
histological work; and M. Suzuki for her administrative help. We also
thank M. Takei and Y. Hirata in the Equipment Developing Group, Research
Institute for Electronic Science, for manufacturing equipment.
NR 65
TC 0
Z9 0
U1 4
U2 6
PU SOC NEUROSCIENCE
PI WASHINGTON
PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA
SN 0270-6474
J9 J NEUROSCI
JI J. Neurosci.
PD JUN 29
PY 2016
VL 36
IS 26
BP 7066
EP 7074
DI 10.1523/JNEUROSCI.0733-16.2016
PG 9
WC Neurosciences
SC Neurosciences & Neurology
GA DQ2GJ
UT WOS:000379020200020
PM 27358462
ER
PT J
AU Mikita, N
Simonoff, E
Pine, DS
Goodman, R
Artiges, E
Banaschewski, T
Bokde, AL
Bromberg, U
Buchel, C
Cattrell, A
Conrod, PJ
Desrivieres, S
Flor, H
Frouin, V
Gallinat, J
Garavan, H
Heinz, A
Ittermann, B
Jurk, S
Martinot, JL
Martinot, MLP
Nees, F
Orfanos, DP
Paus, T
Poustka, L
Smolka, MN
Walter, H
Whelan, R
Schumann, G
Stringaris, A
AF Mikita, N.
Simonoff, E.
Pine, D. S.
Goodman, R.
Artiges, E.
Banaschewski, T.
Bokde, A. L.
Bromberg, U.
Buechel, C.
Cattrell, A.
Conrod, P. J.
Desrivieres, S.
Flor, H.
Frouin, V.
Gallinat, J.
Garavan, H.
Heinz, A.
Ittermann, B.
Jurk, S.
Martinot, J. L.
Martinot, M. L. Paillere
Nees, F.
Orfanos, D. Papadopoulos
Paus, T.
Poustka, L.
Smolka, M. N.
Walter, H.
Whelan, R.
Schumann, G.
Stringaris, A.
TI Disentangling the autism - anxiety overlap: fMRI of reward processing in
a community-based longitudinal study
SO TRANSLATIONAL PSYCHIATRY
LA English
DT Article
ID EVENT-RELATED FMRI; WELL-BEING ASSESSMENT; SPECTRUM DISORDERS;
PREFRONTAL CORTEX; PSYCHIATRIC-DISORDERS; RESPONSE-INHIBITION; NEURAL
MECHANISMS; COGNITIVE CONTROL; DECISION-MAKING; TWIN SAMPLE
AB Up to 40% of youth with autism spectrum disorder (ASD) also suffer from anxiety, and this comorbidity is linked with significant functional impairment. However, the mechanisms of this overlap are poorly understood. We investigated the interplay between ASD traits and anxiety during reward processing, known to be affected in ASD, in a community sample of 1472 adolescents (mean age = 14.4 years) who performed a modified monetary incentive delay task as part of the Imagen project. Blood-oxygen-level dependent (BOLD) responses to reward anticipation and feedback were compared using a 2x2 analysis of variance test (ASD traits: low/high; anxiety symptoms: low/high), controlling for plausible covariates. In addition, we used a longitudinal design to assess whether neural responses during reward processing predicted anxiety at 2-year follow-up. High ASD traits were associated with reduced BOLD responses in dorsal prefrontal regions during reward anticipation and negative feedback. Participants with high anxiety symptoms showed increased lateral prefrontal responses during anticipation, but decreased responses following feedback. Interaction effects revealed that youth with combined ASD traits and anxiety, relative to other youth, showed high right insula activation when anticipating reward, and low right-sided caudate, putamen, medial and lateral prefrontal activations during negative feedback (all clusters P-FWE < 0.05). BOLD activation patterns in the right dorsal cingulate and right medial frontal gyrus predicted new-onset anxiety in participants with high but not low ASD traits. Our results reveal both quantitatively enhanced and qualitatively distinct neural correlates underlying the comorbidity between ASD traits and anxiety. Specific neural responses during reward processing may represent a risk factor for developing anxiety in ASD youth.
C1 [Mikita, N.; Simonoff, E.; Goodman, R.; Stringaris, A.] Kings Coll London, Dept Child & Adolescent Psychiat, Inst Psychiat Psychol & Neurosci, London, England.
[Simonoff, E.] Kings Coll London, NIHR Biomed Res Ctr, London, England.
[Simonoff, E.] Kings Coll London, Dementia Unit South London, London, England.
[Simonoff, E.] Kings Coll London, Maudsley NHS Fdn Trust, London, England.
[Simonoff, E.] Kings Coll London, Inst Psychiat Psychol & Neurosci, London, England.
[Pine, D. S.] NIMH, Sect Dev & Affect Neurosci, Bethesda, MD 20892 USA.
[Artiges, E.; Martinot, J. L.; Martinot, M. L. Paillere] Serv Hosp Freder Joliot, INSERM, Unit Neuroimaging & Psychiat 1000, Orsay, France.
[Artiges, E.; Martinot, J. L.; Martinot, M. L. Paillere] Univ Paris 11, Orsay, France.
[Artiges, E.; Martinot, J. L.; Martinot, M. L. Paillere] Univ Paris 05, Sorbonne Paris Cite, Paris, France.
[Artiges, E.] Orsay Hosp, Dept Psychiat, Orsay, France.
[Banaschewski, T.] Heidelberg Univ, Med Fac Mannheim, Cent Inst Mental Hlth, Dept Child & Adolescent Psychiat & Psychot, Mannheim, Germany.
[Bokde, A. L.] Trinity Coll Dublin, Discipline Psychiat, Sch Med, Dublin, Ireland.
[Bokde, A. L.] Trinity Coll Dublin, Trinity Coll Inst Neurosci, Dublin, Ireland.
[Bromberg, U.; Buechel, C.] Univ Med Ctr Hamburg Eppendorf, Hamburg, Germany.
[Cattrell, A.; Desrivieres, S.; Schumann, G.] Kings Coll London, Inst Psychiat Psychol & Neurosci, MRC, Social Genet & Dev Psychiat Ctr, London, England.
[Conrod, P. J.] Univ Montreal, CHU Ste Justine Hosp, Dept Psychiat, Montreal, PQ, Canada.
[Conrod, P. J.] Kings Coll London, Inst Psychiat Psychol & Neurosci, Dept Psychol Med & Psychiat, London, England.
[Flor, H.; Nees, F.] Heidelberg Univ, Med Fac Mannheim, Cent Inst Mental Hlth, Dept Cognit & Clin Neurosci, Mannheim, Germany.
[Frouin, V.; Orfanos, D. Papadopoulos] CEA Saclay, Commissariat Energie Atom, Neurospin, Saclay Ctr, Paris, France.
[Gallinat, J.] Univ Med Ctr Hamburg Eppendorf, Dept Psychiat & Psychotherapy, Hamburg, Germany.
[Garavan, H.] Univ Vermont, Dept Psychiat, Burlington, VT USA.
[Garavan, H.] Univ Vermont, Dept Psychol, Burlington, VT 05405 USA.
[Heinz, A.; Walter, H.] Charite, Dept Psychiat & Psychotherapy, Campus Charite Mitte, Berlin, Germany.
[Ittermann, B.] Phys Tech Bundesanstalt, Braunschweig, Germany.
[Jurk, S.; Smolka, M. N.] Tech Univ Dresden, Dept Psychiat & Neuroimaging Ctr, Dresden, Germany.
[Martinot, J. L.; Martinot, M. L. Paillere] Cochin Hosp, AP HP, Dept Adolescent Psychopathol & Med, Maison Solenn, Paris, France.
[Paus, T.] Baycrest, Rotman Res Inst, Toronto, ON, Canada.
[Paus, T.] Child Mind Inst, New York, NY USA.
[Paus, T.] Univ Toronto, Dept Psychol, Toronto, ON, Canada.
[Paus, T.] Univ Toronto, Dept Psychiat, Toronto, ON, Canada.
[Poustka, L.] Med Univ Vienna, Dept Child & Adolescent Psychiat & Psychotherapy, Vienna, Austria.
[Whelan, R.] Univ Coll Dublin, Dept Psychol, Dublin, Ireland.
RP Mikita, N (reprint author), Kings Coll London, Dept Child & Adolescent Psychiat, Inst Psychiat Psychol & Neurosci, PO85, Crespigny Pk, London SE5 8AF, England.
EM nina.mikita@kcl.ac.uk
RI Poustka, Luise/D-9299-2017;
OI Flor, Herta/0000-0003-4809-5398
FU European Union-funded FP6 Integrated Project IMAGEN
(reinforcement-related behaviour in normal brain function and
psychopathology) [LSHM-CT- 2007-037286]; FP7 project IMAGE-MEND (IMAging
GEnetics for MENtal Disorders) [602450]; FP7 project AGGRESSOTYPE
[602805]; FP7 project MATRICS [603016]; Innovative Medicine Initiative
Project EU-AIMS [115300-2]; Medical Research Council Grants
'Developmental pathways into adolescent substance abuse' [93558];
Consortium on Vulnerability to Externalizing Disorders and Addictions
(c-VEDA) [MR/N000390/1]; Swedish funding agency VR; Swedish funding
agency FORTE; Swedish funding agency FORMAS; Medical Research Council;
Wellcome Trust (Behavioural and Clinical Neuroscience Institute,
University of Cambridge, Cambridge, UK); National Institute for Health
Research (NIHR) Biomedical Research Centre at South London; Maudsley NHS
Foundation Trust and King's College London; Bundesministeriumfur Bildung
und Forschung (BMBF Forschungsnetz AERIAL) [01GS08152, 01EV0711, eMED
SysAlc01ZX1311A]; Deutsche Forschungsgemeinschaft (DFG) [SM 80/7-1, SM
80/7-2, SFB 940/1]; ANR [AF12-NEUR0008-01-WM2NA, ANR-12-SAMA-0004];
Fondation de France; Fondation pour la Recherche Medicale; Mission
Interministerielle de
Lutte-contre-les-Drogues-et-les-Conduites-Addictives (MILDECA);
Assistance-Publique-Hopitaux-de-Paris; INSERM (interface grant); Paris
Sud University IDEX; National Institutes of Health, USA (Axon,
Testosterone and Mental Health during Adolescence) [RO1 MH085772-01A1];
NIH Consortium grant [U54 EB020403]; cross-NIH alliance; Wellcome Trust
FX This work received support from the following sources: the European
Union-funded FP6 Integrated Project IMAGEN (reinforcement-related
behaviour in normal brain function and psychopathology) (LSHM-CT-
2007-037286), the FP7 projects IMAGE-MEND (602450; IMAging GEnetics for
MENtal Disorders), AGGRESSOTYPE (602805) and MATRICS (603016), the
Innovative Medicine Initiative Project EU-AIMS (115300-2), the Medical
Research Council Grants 'Developmental pathways into adolescent
substance abuse' (93558) and Consortium on Vulnerability to
Externalizing Disorders and Addictions (c-VEDA) (MR/N000390/1), the
Swedish funding agencies VR, FORTE and FORMAS, the Medical Research
Council and the Wellcome Trust (Behavioural and Clinical Neuroscience
Institute, University of Cambridge, Cambridge, UK), the National
Institute for Health Research (NIHR) Biomedical Research Centre at South
London and Maudsley NHS Foundation Trust and King's College London, the
Bundesministeriumfur Bildung und Forschung (BMBF grants 01GS08152;
01EV0711; eMED SysAlc01ZX1311A; Forschungsnetz AERIAL) and the Deutsche
Forschungsgemeinschaft (DFG grants SM 80/7-1, SM 80/7-2, SFB 940/1).
Further support was provided by grants from ANR (project
AF12-NEUR0008-01-WM2NA, and ANR-12-SAMA-0004), the Fondation de France,
the Fondation pour la Recherche Medicale, the Mission Interministerielle
de Lutte-contre-les-Drogues-et-les-Conduites-Addictives (MILDECA), the
Assistance-Publique-Hopitaux-de-Paris and INSERM (interface grant),
Paris Sud University IDEX 2012, the National Institutes of Health, USA
(Axon, Testosterone and Mental Health during Adolescence; RO1
MH085772-01A1), and by NIH Consortium grant U54 EB020403, supported by a
cross-NIH alliance that funds Big Data to Knowledge Centres of
Excellence. Dr Stringaris gratefully acknowledges funding from the
Wellcome Trust.
NR 88
TC 0
Z9 0
U1 20
U2 20
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 2158-3188
J9 TRANSL PSYCHIAT
JI Transl. Psychiatr.
PD JUN 28
PY 2016
VL 6
AR e845
DI 10.1038/tp.2016.107
PG 10
WC Psychiatry
SC Psychiatry
GA DW1QW
UT WOS:000383418700002
PM 27351599
ER
PT J
AU Mena, I
Nelson, MI
Quezada-Monroy, F
Dutta, J
Cortes-Fernandez, R
Lara-Puente, JH
Castro-Peralta, F
Cunha, LF
Trovao, NS
Lozano-Dubernard, B
Rambaut, A
van Bakel, H
Garcia-Sastre, A
AF Mena, Ignacio
Nelson, Martha I.
Quezada-Monroy, Francisco
Dutta, Jayeeta
Cortes-Fernandez, Refugio
Horacio Lara-Puente, J.
Castro-Peralta, Felipa
Cunha, Luis F.
Trovao, Nidia S.
Lozano-Dubernard, Bernardo
Rambaut, Andrew
van Bakel, Harm
Garcia-Sastre, Adolfo
TI Origins of the 2009 H1N1 influenza pandemic in swine in Mexico
SO ELIFE
LA English
DT Article
ID A VIRUSES; TRANSMISSION DYNAMICS; UNITED-STATES; EVOLUTION; ALIGNMENT;
FERRETS; PIGS; HEMAGGLUTININ; ESTABLISHMENT; REASSORTMENT
AB Asia is considered an important source of influenza A virus (IAV) pandemics, owing to large, diverse viral reservoirs in poultry and swine. However, the zoonotic origins of the 2009 A/H1N1 influenza pandemic virus (pdmH1N1) remain unclear, due to conflicting evidence from swine and humans. There is strong evidence that the first human outbreak of pdmH1N1 occurred in Mexico in early 2009. However, no related swine viruses have been detected in Mexico or any part of the Americas, and to date the most closely related ancestor viruses were identified in Asian swine. Here, we use 58 new whole-genome sequences from IAVs collected in Mexican swine to establish that the swine virus responsible for the 2009 pandemic evolved in central Mexico. This finding highlights how the 2009 pandemic arose from a region not considered a pandemic risk, owing to an expansion of IAV diversity in swine resulting from long-distance live swine trade.
C1 [Mena, Ignacio; Cunha, Luis F.; Garcia-Sastre, Adolfo] Icahn Sch Med Mt Sinai, Dept Microbiol, New York, NY 10029 USA.
[Mena, Ignacio; Trovao, Nidia S.; Garcia-Sastre, Adolfo] Icahn Sch Med Mt Sinai, Global Hlth & Emerging Pathogens Inst, New York, NY 10029 USA.
[Nelson, Martha I.; Trovao, Nidia S.; Rambaut, Andrew] NIH, Div Int Epidemiol & Populat Studies, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Quezada-Monroy, Francisco; Cortes-Fernandez, Refugio; Horacio Lara-Puente, J.; Castro-Peralta, Felipa; Lozano-Dubernard, Bernardo] Lab Avi Mex, Mexico City, DF, Mexico.
[Dutta, Jayeeta; Cunha, Luis F.; van Bakel, Harm] Icahn Sch Med Mt Sinai, Genet & Genom Sci, New York, NY 10029 USA.
[Trovao, Nidia S.] Univ Leuven, Rega Inst, Dept Microbiol & Immunol, Leuven, Belgium.
[Rambaut, Andrew] Univ Edinburgh, Inst Evolutionary Biol, Edinburgh, Midlothian, Scotland.
[Rambaut, Andrew] Univ Edinburgh, Ctr Immunol Infect & Evolut, Edinburgh, Midlothian, Scotland.
[Garcia-Sastre, Adolfo] Icahn Sch Med Mt Sinai, Div Infect Dis, Dept Med, New York, NY 10029 USA.
RP Garcia-Sastre, A (reprint author), Icahn Sch Med Mt Sinai, Dept Microbiol, New York, NY 10029 USA.; Garcia-Sastre, A (reprint author), Icahn Sch Med Mt Sinai, Global Hlth & Emerging Pathogens Inst, New York, NY 10029 USA.; Garcia-Sastre, A (reprint author), Icahn Sch Med Mt Sinai, Div Infect Dis, Dept Med, New York, NY 10029 USA.
EM adolfo.garcia-sastre@mssm.edu
OI Mena, Ignacio/0000-0001-5464-7086; Garcia-Sastre,
Adolfo/0000-0002-6551-1827; Sequeira Trovao, Nidia/0000-0002-2106-1166
FU National Institutes of Health Centers of Excellence for Influenza
Research and Surveillance [HHSN272201400008C]; Fogarty International
Center Multinational Influenza Seasonal Mortality Study
FX National Institutes of Health Centers of Excellence for Influenza
Research and Surveillance, Contract No. HHSN272201400008C Adolfo
Garcia-Sastre; Fogarty International Center Multinational Influenza
Seasonal Mortality Study Martha I Nelson; The funders had no role in
study design, data collection and interpretation, or the decision to
submit the work for publication.
NR 55
TC 0
Z9 0
U1 5
U2 10
PU ELIFE SCIENCES PUBLICATIONS LTD
PI CAMBRIDGE
PA SHERATON HOUSE, CASTLE PARK, CAMBRIDGE, CB3 0AX, ENGLAND
SN 2050-084X
J9 ELIFE
JI eLife
PD JUN 28
PY 2016
VL 5
AR e16777
DI 10.7554/eLife.16777
PG 21
WC Biology
SC Life Sciences & Biomedicine - Other Topics
GA DS6VI
UT WOS:000380920700001
ER
PT J
AU Kim, G
Levine, RL
AF Kim, Geumsoo
Levine, Rodney L.
TI A Methionine Residue Promotes Hyperoxidation of the Catalytic Cysteine
of Mouse Methionine Sulfoxide Reductase A
SO BIOCHEMISTRY
LA English
DT Article
ID ESCHERICHIA-COLI; OXIDATIVE DAMAGE; ACTIVE-SITE; PROTEIN; MECHANISM;
INTERMEDIATE; BIOCHEMISTRY; ENZYMES; SULFUR; ROLES
AB Methionine sulfoxide reductase A (msrA) reduces methionine sulfoxide in proteins back to methionine. Its, catalytic cysteine (Cys72-SH) has a low pK(a) that facilitates oxidation by methionine sulfoxide to cysteine sulfenic acid. If the catalytic cycle proceeds efficiently, the sulfenic acid is reduced back to cysteine at the expense of thioredoxin. However, the sulfenic acid is vulnerable to "irreversible" oxidation to cysteine sulfinic acid that inactivates msrA (hyperoxidation). We observed that human msrA is resistant to hyperoxidation while mouse msrA is readily hyperoxidized by micromolar concentrations of hydrogen peroxide. We investigated the basis of this difference in susceptibility to hyperoxidation and established that it is controlled by the presence or absence of a Met residue in the carboxyl-terminal domain of the enzyme, Met229. This residue is Val in human msrA, and when it was mutated to Met, human msrA became sensitive to hyperoxidation. Conversely, mouse msrA was rendered insensitive to hyperoxidation when Met229 was mutated to Val or one of five other residues. Positioning of the methionine at residue 229 is not critical, as hyperoxidation occurred as long as the methionine was located within the group of 14 carboxyl-terminal residues. The carboxyl domain of msrA is known to be flexible and to have access to the active site, and Met residues are known to form stable, noncovalent bonds with aromatic residues through interaction of the sulfur atom with the aromatic ring. We propose that Met229 forms-such a bond with Trp74 at the active site, preventing formation of a protective sulfenylamide with Cys72 sulfenic acid. As a consequence, the sulfenic acid is available for facile, irreversible oxidation to cysteine sulfinic acid.
C1 [Kim, Geumsoo; Levine, Rodney L.] NHLBI, Biochem Lab, Bldg 3, Bethesda, MD 20892 USA.
RP Levine, RL (reprint author), NIH, Bldg 50,Room 2351, Bethesda, MD 20892 USA.
EM rlevine@nih.gov
RI Levine, Rodney/D-9885-2011
FU Intramural Research Division of the National Heart, Lung, and Blood
Institute [ZIA HL000225]
FX This research was supported by the Intramural Research Division of the
National Heart, Lung, and Blood Institute (ZIA HL000225).
NR 32
TC 0
Z9 0
U1 1
U2 2
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0006-2960
J9 BIOCHEMISTRY-US
JI Biochemistry
PD JUN 28
PY 2016
VL 55
IS 25
BP 3586
EP 3593
DI 10.1021/acs.biochem.6b00180
PG 8
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA DQ1PS
UT WOS:000378973500010
PM 27259041
ER
PT J
AU Wang, YB
Hersheson, J
Lopez, D
Hammer, M
Liu, Y
Lee, KH
Pinto, V
Seinfeld, J
Wiethoff, S
Sun, JD
Amouri, R
Hentati, F
Baudry, N
Tran, J
Singleton, AB
Coutelier, M
Brice, A
Stevanin, G
Durr, A
Bi, XN
Houlden, H
Baudry, M
AF Wang, Yubin
Hersheson, Joshua
Lopez, Dulce
Hammer, Monia
Liu, Yan
Lee, Ka-Hung
Pinto, Vanessa
Seinfeld, Jeff
Wiethoff, Sarah
Sun, Jiandong
Amouri, Rim
Hentati, Faycal
Baudry, Neema
Tran, Jennifer
Singleton, Andrew B.
Coutelier, Marie
Brice, Alexis
Stevanin, Giovanni
Durr, Alexandra
Bi, Xiaoning
Houlden, Henry
Baudry, Michel
TI Defects in the CAPN1 Gene Result in Alterations in Cerebellar
Development and Cerebellar Ataxia in Mice and Humans
SO CELL REPORTS
LA English
DT Article
ID D-ASPARTATE RECEPTORS; GRANULE CELLS; SYNAPTIC PLASTICITY; RAT-BRAIN;
TUMOR-SUPPRESSOR; DEFICIENT MICE; MUTANT MOUSE; MU-CALPAIN; ACTIVATION;
SURVIVAL
AB A CAPN1 missense mutation in Parson Russell Terrier dogs is associated with spinocerebellar ataxia. We now report that homozygous or heterozygous CAPN1-null mutations in humans result in cerebellar ataxia and limb spasticity in four independent pedigrees. Calpain-1 knockout (KO) mice also exhibit a mild form of ataxia due to abnormal cerebellar development, including enhanced neuronal apoptosis, decreased number of cerebellar granule cells, and altered synaptic transmission. Enhanced apoptosis is due to absence of calpain-1-mediated cleavage of PH domain and leucine-rich repeat protein phosphatase 1 (PHLPP1), which results in inhibition of the Akt pro-survival pathway in developing granule cells. Injection of neonatal mice with the indirect Akt activator, bisperoxovanadium, or crossing calpain-1 KO mice with PHLPP1 KO mice prevented increased postnatal cerebellar granule cell apoptosis and restored granule cell density and motor coordination in adult mice. Thus, mutations in CAPN1 are an additional cause of ataxia in mammals, including humans.
C1 [Wang, Yubin; Lopez, Dulce; Liu, Yan; Lee, Ka-Hung; Seinfeld, Jeff; Baudry, Neema; Tran, Jennifer; Baudry, Michel] Western Univ Hlth Sci, Grad Coll Biomed Sci, Pomona, CA 91766 USA.
[Pinto, Vanessa; Sun, Jiandong; Bi, Xiaoning] Western Univ Hlth Sci, Coll Osteopath Med Pacific, Pomona, CA 91766 USA.
[Hersheson, Joshua; Wiethoff, Sarah; Houlden, Henry] Natl Hosp Neurol & Neurosurg, Queen Sq, London WC1N 3BG, England.
[Hersheson, Joshua; Wiethoff, Sarah; Houlden, Henry] UCL Inst Neurol, Queen Sq, London WC1N 3BG, England.
[Wiethoff, Sarah] Univ Tubingen, Ctr Neurol, D-72076 Tubingen, Germany.
[Wiethoff, Sarah] Univ Tubingen, Hertie Inst Clin Brain Res, D-72076 Tubingen, Germany.
[Hammer, Monia; Amouri, Rim; Hentati, Faycal] Natl Inst Neurol, Dept Mol Neurobiol & Neuropathol, Tunis 1007, Tunisia.
[Hammer, Monia; Singleton, Andrew B.] NIH, Neurogenet Lab, Bldg 10, Bethesda, MD 20892 USA.
[Coutelier, Marie; Brice, Alexis; Stevanin, Giovanni; Durr, Alexandra] Univ Paris 06, INSERM U1127, CNRS UMR 7225, Sorbonne Univ,Inst Cerveau & Moelle Epiniere,UMRS, F-75013 Paris, France.
[Coutelier, Marie] Catholic Univ Louvain, Lab Human Mol Genet, de Duve Inst, B-1200 Brussels, Belgium.
[Coutelier, Marie; Stevanin, Giovanni] Paris Sci & Lettres PSL Res Univ, EPHE, F-75013 Paris, France.
[Brice, Alexis; Stevanin, Giovanni; Durr, Alexandra] Hop La Pitie Salpetriere, AP HP, Ctr Reference Neurogenet, F-75013 Paris, France.
RP Baudry, M (reprint author), Western Univ Hlth Sci, Grad Coll Biomed Sci, Pomona, CA 91766 USA.; Houlden, H (reprint author), Natl Hosp Neurol & Neurosurg, Queen Sq, London WC1N 3BG, England.
EM h.houlden@ucl.ac.uk; mbaudry@westernu.edu
RI Houlden, Henry/C-1532-2008;
OI Houlden, Henry/0000-0002-2866-7777; Coutelier, Marie/0000-0002-0261-7210
FU NINDS [P01NS045260-01]; Medical Research Council UK; Brain Research
Trust; Wellcome Trust; NIHR UCL/UCLH BRC; Agence Nationale de la
Recherche (ANR); Verum Foundation; patient association Connaitre les
Syndromes Cerebelleux; Roger de Spoelberg Foundation; European Union;
program Investissements d'avenir [ANR-10-IAIHU-06]; Western University
of Health Sciences; Daljit and Elaine Sarkaria Chair; Fond National de
la Recherche Scientifique (aspirant FNRS)
FX This work was supported by grant P01NS045260-01 from NINDS (PI: Dr. C.M.
Gall), the Medical Research Council UK, Brain Research Trust, Wellcome
Trust, NIHR UCL/UCLH BRC, the Agence Nationale de la Recherche (ANR; to
G.S.), the Verum Foundation (to G.S. and A.B.), the patient association
Connaitre les Syndromes Cerebelleux (CSC; to G.S.), the Roger de
Spoelberg Foundation (to A.B.), and the European Union (Omics call:
NEUROMICS, to A.B. and A.D.) and benefited from the program
Investissements d'avenir ANR-10-IAIHU-06 (to the ICM Institute). The
authors want to thank Western University of Health Sciences for the
financial support to M.B. X.B. is also supported by funds from the
Daljit and Elaine Sarkaria Chair. M.C. was the recipient of a fellowship
from the Fond National de la Recherche Scientifique (aspirant FNRS). The
authors are grateful to Claire Sophie Davoine and to the DNA and cell
biobank of the ICM institute for their technical assistance.
NR 45
TC 5
Z9 5
U1 1
U2 3
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 2211-1247
J9 CELL REP
JI Cell Reports
PD JUN 28
PY 2016
VL 16
IS 1
BP 79
EP 91
DI 10.1016/j.celrep.2016.05.044
PG 13
WC Cell Biology
SC Cell Biology
GA DQ1GY
UT WOS:000378950700009
PM 27320912
ER
PT J
AU Zaaijer, S
Shaikh, N
Nageshan, RK
Cooper, JP
AF Zaaijer, Sophie
Shaikh, Nadeem
Nageshan, Rishi Kumar
Cooper, Julia Promisel
TI Rif1 Regulates the Fate of DNA Entanglements during Mitosis
SO CELL REPORTS
LA English
DT Article
ID ULTRAFINE ANAPHASE BRIDGES; PROTEIN PHOSPHATASE 1; FISSION YEAST;
DYSFUNCTIONAL TELOMERES; CHROMOSOME SEGREGATION; REPLICATION STRESS;
GLOBAL REGULATOR; TAZ1; CHECKPOINT; 53BP1
AB Clearance of entangled DNA from the anaphase mid-region must accurately proceed in order for chromosomes to segregate with high fidelity. Loss of Taz1 (fission yeast ortholog of human TRF1/TRF2) leads to stalled telomeric replication forks that trigger telomeric entanglements; the resolution of these entanglements fails at <= 20 degrees C. Here, we investigate these entanglements and their promotion by the conserved replication/repair protein Rif1. Rif1 plays no role in taz1 Delta fork stalling. Rather, Rif1 localizes to the anaphase mid-region and regulates the resolution of persisting DNA structures. This anaphase role for Rif1 is genetically separate from the role of Rif1 in S/G2, though both roles require binding to PP1 phosphatase, implying spatially and temporally distinct Rif1-regulated phosphatase substrates. Rif1 thus acts as a double-edged sword. Although it inhibits the resolution of taz1 Delta telomere entanglements, it promotes the resolution of non-telomeric ultrafine anaphase bridges at <= 20 degrees C We suggest a unifying model for Rif1's seemingly diverse roles in chromosome segregation in eukaryotes.
C1 [Zaaijer, Sophie; Shaikh, Nadeem; Nageshan, Rishi Kumar; Cooper, Julia Promisel] NCI, Biochem & Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Zaaijer, Sophie] New York Genome Ctr, 101 Ave Amer, New York, NY 10013 USA.
RP Cooper, JP (reprint author), NCI, Biochem & Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM julie.cooper@nih.gov
FU Cancer Research UK; National Cancer Institute
FX We thank all members of the J.P.C. lab for useful discussion and
experimental help, and special thanks for advice go to our former lab
members Jessica Greenwood and Ofer Rog. We thank Alexander Kelly for
valuable discussion and Alessandro Bianchi and Miguel Godinho Ferreira
for kind gifts of reagents and advice. This work was supported by Cancer
Research UK and the National Cancer Institute.
NR 45
TC 2
Z9 2
U1 3
U2 5
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 2211-1247
J9 CELL REP
JI Cell Reports
PD JUN 28
PY 2016
VL 16
IS 1
BP 148
EP 160
DI 10.1016/j.celrep.2016.05.077
PG 13
WC Cell Biology
SC Cell Biology
GA DQ1GY
UT WOS:000378950700014
PM 27320927
ER
PT J
AU Lu, HM
Shamanna, RA
Keijzers, G
Anand, R
Rasmussen, LJ
Cejka, P
Croteau, DL
Bohr, VA
AF Lu, Huiming
Shamanna, Raghavendra A.
Keijzers, Guido
Anand, Roopesh
Rasmussen, Lene Juel
Cejka, Petr
Croteau, Deborah L.
Bohr, Vilhelm A.
TI RECQL4 Promotes DNA End Resection in Repair of DNA Double-Strand Breaks
SO CELL REPORTS
LA English
DT Article
ID ROTHMUND-THOMSON-SYNDROME; HOMOLOGOUS RECOMBINATION; PATHWAY CHOICE;
MRE11-RAD50-NBS1 COMPLEX; SYNDROME PROTEIN; MAMMALIAN-CELLS; MRE11
NUCLEASE; EXONUCLEASE 1; HELICASE; REPLICATION
AB The RecQ helicase RECQL4, mutated in Rothmund-Thomson syndrome, regulates genome stability, aging, and cancer. Here, we identify a crucial role for RECQL4 in DNA end resection, which is the initial and an essential step of homologous recombination (HR)-dependent DNA double-strand break repair (DSBR). Depletion of RECQL4 severely reduces HR-mediated repair and 50 end resection in vivo. RECQL4 physically interacts with MRE11-RAD50-NBS1 (MRN), which senses DSBs and initiates DNA end resection with CtIP. The MRE11 exonuclease regulates the retention of RECQL4 at laser-induced DSBs. RECQL4 also directly interacts with CtIP via its N-terminal domain and promotes CtIP recruitment to the MRN complex at DSBs. Moreover, inactivation of RECQL4's helicase activity impairs DNA end processing and HR-dependent DSBR without affecting its interaction with MRE11 and CtIP, suggesting an important role for RECQL4's unwinding activity in the process. Thus, we report that RECQL4 is an important participant in HR-dependent DSBR.
C1 [Lu, Huiming; Shamanna, Raghavendra A.; Croteau, Deborah L.; Bohr, Vilhelm A.] NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA.
[Keijzers, Guido; Rasmussen, Lene Juel; Bohr, Vilhelm A.] Univ Copenhagen, Ctr Hlth Aging, DK-2200 Copenhagen, Denmark.
[Keijzers, Guido; Rasmussen, Lene Juel; Bohr, Vilhelm A.] Univ Copenhagen, Dept Cellular & Mol Med, DK-2200 Copenhagen, Denmark.
[Anand, Roopesh; Cejka, Petr] Univ Zurich, Inst Mol Canc Res, Winterthurerstr 190, CH-8057 Zurich, Switzerland.
RP Bohr, VA (reprint author), NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA.; Bohr, VA (reprint author), Univ Copenhagen, Ctr Hlth Aging, DK-2200 Copenhagen, Denmark.; Bohr, VA (reprint author), Univ Copenhagen, Dept Cellular & Mol Med, DK-2200 Copenhagen, Denmark.
EM vbohr@nih.gov
FU Intramural Research Program of the NIH, National Institute on Aging
FX AID-DIVA U2OS is under MTA between Dr. Gaelle Legube and NIA. We thank
Dr. Xiaofan Wang for DR-GFP U2OS, Drs. Dik van Gent and Roland Kanaar
for YFP-MRE11 plasmid, Dr. Marc Wold for the GFP-RPA plasmids, Dr.
Binghui Shen for FLAG-DNA2 plasmid, Dr. Tomasz Kulikowicz and
Christopher Dunn for RECQL4 protein, Tomasz Kulikowicz and Alfred May
for IR operation, and Drs. Morten Scheibye-Knudsen and Jaya Sarkar for
their critical comments. This research was supported entirely by the
Intramural Research Program of the NIH, National Institute on Aging.
NR 56
TC 3
Z9 3
U1 4
U2 7
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 2211-1247
J9 CELL REP
JI Cell Reports
PD JUN 28
PY 2016
VL 16
IS 1
BP 161
EP 173
DI 10.1016/j.celrep.2016.05.079
PG 13
WC Cell Biology
SC Cell Biology
GA DQ1GY
UT WOS:000378950700015
PM 27320928
ER
PT J
AU Savidis, G
McDougall, WM
Meraner, P
Perreira, JM
Portmann, JM
Trincucci, G
John, SP
Aker, AM
Renzette, N
Robbins, DR
Guo, ZR
Green, S
Kowalik, TF
Brass, AL
AF Savidis, George
McDougall, William M.
Meraner, Paul
Perreira, Jill M.
Portmann, Jocelyn M.
Trincucci, Gaia
John, Sinu P.
Aker, Aaron M.
Renzette, Nicholas
Robbins, Douglas R.
Guo, Zhiru
Green, Sharone
Kowalik, Timothy F.
Brass, Abraham L.
TI Identification of Zika Virus and Dengue Virus Dependency Factors using
Functional Genomics
SO CELL REPORTS
LA English
DT Article
ID PHOSPHATIDYLSERINE RECEPTORS; ENDOPLASMIC-RETICULUM; GENES; CELLS;
REPLICATION; INFECTION; CRISPR-CAS9; SCREEN; ENTRY; RNAI
AB The flaviviruses dengue virus (DENV) and Zika virus (ZIKV) are severe health threats with rapidly expanding ranges. To identify the host cell dependencies of DENV and ZIKV, we completed orthologous functional genomic screens using RNAi and CRISPR/Cas9 approaches. The screens recovered the ZIKV entry factor AXL as well as multiple host factors involved in endocytosis (RAB5C and RABGEF), heparin sulfation (NDST1 and EXT1), and transmembrane protein processing and maturation, including the endoplasmic reticulum membrane complex (EMC). We find that both flaviviruses require the EMC for their early stages of infection. Together, these studies generate a high-confidence, systems-wide view of human-flavivirus interactions and provide insights into the role of the EMC in flavivirus replication.
C1 [Savidis, George; McDougall, William M.; Meraner, Paul; Perreira, Jill M.; Portmann, Jocelyn M.; Trincucci, Gaia; Aker, Aaron M.; Renzette, Nicholas; Robbins, Douglas R.; Kowalik, Timothy F.; Brass, Abraham L.] Univ Massachusetts Med, Dept Microbiol & Physiol Syst MaPS, Worcester, MA 01655 USA.
[John, Sinu P.] NIAID, Signaling Syst Unit, Lab Syst Biol, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Guo, Zhiru; Green, Sharone] Univ Massachusetts, Sch Med, Dept Med, Div Infect Dis & Immunol, Worcester, MA 01655 USA.
[Brass, Abraham L.] Univ Massachusetts, Sch Med, Dept Med, Div Gastroenterol, Worcester, MA 01655 USA.
RP Brass, AL (reprint author), Univ Massachusetts Med, Dept Microbiol & Physiol Syst MaPS, Worcester, MA 01655 USA.; Brass, AL (reprint author), Univ Massachusetts, Sch Med, Dept Med, Div Gastroenterol, Worcester, MA 01655 USA.
EM abraham.brass@umassmed.edu
FU Burroughs Wellcome Foundation; NIAID, NIH [HHSN272200900041C]; UMMS
Center for Clinical and Translational Science; Bill and Melinda Gates
Foundation
FX We thank R.H. Scheuermann and B. Pickett (J. Craig Venter Institute),
the University of Maryland Medical System (UMMS; R. Fish, L. Benson, and
J. Barrett), ICCB-L (C. Shamu, J. Smith, S. Rudnicki, S. Johnston, K.
Rudnicki, and D. Wrobel), and T. Soellner of Heidelberg University for
help and inspiration. This work was supported by an Investigators in the
Pathogenesis of Infectious Disease award from the Burroughs Wellcome
Foundation to A. L. B. and a subcontract to A. L. B. from contract
HHSN272200900041C to Northrup Grumman Corporation from NIAID, NIH.
A.L.B. is grateful to the UMMS Center for Clinical and Translational
Science and to the Bill and Melinda Gates Foundation for their support.
NR 48
TC 23
Z9 23
U1 14
U2 26
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 2211-1247
J9 CELL REP
JI Cell Reports
PD JUN 28
PY 2016
VL 16
IS 1
BP 232
EP 246
DI 10.1016/j.celrep.2016.06.028
PG 15
WC Cell Biology
SC Cell Biology
GA DQ1GY
UT WOS:000378950700021
PM 27342126
ER
PT J
AU Allott, EH
Geradts, J
Sun, XZ
Cohen, SM
Zirpoli, GR
Khoury, T
Bshara, W
Chen, MJ
Sherman, ME
Palmer, JR
Ambrosone, CB
Olshan, AF
Troester, MA
AF Allott, Emma H.
Geradts, Joseph
Sun, Xuezheng
Cohen, Stephanie M.
Zirpoli, Gary R.
Khoury, Thaer
Bshara, Wiam
Chen, Mengjie
Sherman, Mark E.
Palmer, Julie R.
Ambrosone, Christine B.
Olshan, Andrew F.
Troester, Melissa A.
TI Intratumoral heterogeneity as a source of discordance in breast cancer
biomarker classification
SO BREAST CANCER RESEARCH
LA English
DT Article
DE Automated algorithm; Digital pathology; Discordance; Estrogen receptor;
HER2; Immunohistochemistry; Intratumoral heterogeneity; Progesterone
receptor; Tissue microarray
ID IN-SITU HYBRIDIZATION; ESTROGEN-RECEPTOR; PROGESTERONE-RECEPTORS;
FORMALIN FIXATION; AMBER CONSORTIUM; IMMUNOHISTOCHEMISTRY; HER2;
CARCINOMAS; SPECIMENS; TUMOR
AB Background: Spatial heterogeneity in biomarker expression may impact breast cancer classification. The aims of this study were to estimate the frequency of spatial heterogeneity in biomarker expression within tumors, to identify technical and biological factors contributing to spatial heterogeneity, and to examine the impact of discordant biomarker status within tumors on clinical record agreement.
Methods: Tissue microarrays (TMAs) were constructed using two to four cores (1.0 mm) for each of 1085 invasive breast cancers from the Carolina Breast Cancer Study, which is part of the AMBER Consortium. Immunohistochemical staining for estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) was quantified using automated digital imaging analysis. The biomarker status for each core and for each case was assigned using clinical thresholds. Cases with core-to-core biomarker discordance were manually reviewed to distinguish intratumoral biomarker heterogeneity from misclassification of biomarker status by the automated algorithm. The impact of core-to-core biomarker discordance on case-level agreement between TMAs and the clinical record was evaluated.
Results: On the basis of automated analysis, discordant biomarker status between TMA cores occurred in 9 %, 16 %, and 18 % of cases for ER, PR, and HER2, respectively. Misclassification of benign epithelium and/or ductal carcinoma in situ as invasive carcinoma by the automated algorithm was implicated in discordance among cores. However, manual review of discordant cases confirmed spatial heterogeneity as a source of discordant biomarker status between cores in 2 %, 7 %, and 8 % of cases for ER, PR, and HER2, respectively. Overall, agreement between TMA and clinical record was high for ER (94 %), PR (89 %), and HER2 (88 %), but it was reduced in cases with core-to-core discordance (agreement 70 % for ER, 61 % for PR, and 57 % for HER2).
Conclusions: Intratumoral biomarker heterogeneity may impact breast cancer classification accuracy, with implications for clinical management. Both manually confirmed biomarker heterogeneity and misclassification of biomarker status by automated image analysis contribute to discordant biomarker status between TMA cores. Given that manually confirmed heterogeneity is uncommon (<10 % of cases), large studies are needed to study the impact of heterogeneous biomarker expression on breast cancer classification and outcomes.
C1 [Allott, Emma H.; Cohen, Stephanie M.; Olshan, Andrew F.; Troester, Melissa A.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA.
[Allott, Emma H.; Sun, Xuezheng; Olshan, Andrew F.; Troester, Melissa A.] Univ N Carolina, Dept Epidemiol, 135 Dauer Dr,CB 7435, Chapel Hill, NC 27599 USA.
[Geradts, Joseph] Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA.
[Zirpoli, Gary R.; Ambrosone, Christine B.] Roswell Pk Canc Inst, Dept Canc Prevent & Control, Buffalo, NY 14263 USA.
[Khoury, Thaer; Bshara, Wiam] Roswell Pk Canc Inst, Dept Pathol, Buffalo, NY 14263 USA.
[Chen, Mengjie] Univ N Carolina, Dept Biostat, Chapel Hill, NC 27599 USA.
[Chen, Mengjie] Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA.
[Sherman, Mark E.] NCI, Canc Prevent Div, Bethesda, MD 20892 USA.
[Palmer, Julie R.] Boston Univ, Slone Epidemiol Ctr, Boston, MA 02215 USA.
RP Troester, MA (reprint author), Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA.; Troester, MA (reprint author), Univ N Carolina, Dept Epidemiol, 135 Dauer Dr,CB 7435, Chapel Hill, NC 27599 USA.
EM troester@unc.edu
FU National Cancer Institute [5P01CA151135-04, P50-CA058223, U01 CA179715,
3P30CA016086]; University Cancer Research Fund at the University of
North Carolina at Chapel Hill; Breast Cancer Research Foundation;
American Institute for Cancer Research; University of North Carolina at
Chapel Hill University Cancer Research Fund
FX This work was supported by the National Cancer Institute (grant
5P01CA151135-04 to the AMBER Consortium: JG, TK, WB, GRZ, JRP, CBA, AFO,
and MAT; grant P50-CA058223 to SPORE in Breast Cancer: MAT and AFO;
grant U01 CA179715 to MAT), by the University Cancer Research Fund at
the University of North Carolina at Chapel Hill (EHA, AFO, and MAT), by
the Breast Cancer Research Foundation (CBA), and by the American
Institute for Cancer Research (EHA). The Translational Pathology
Laboratory (SMC) is supported in part by grants from the National Cancer
Institute (3P30CA016086) and the University of North Carolina at Chapel
Hill University Cancer Research Fund.
NR 33
TC 2
Z9 2
U1 2
U2 5
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1465-542X
EI 1465-5411
J9 BREAST CANCER RES
JI Breast Cancer Res.
PD JUN 28
PY 2016
VL 18
AR 68
DI 10.1186/s13058-016-0725-1
PG 11
WC Oncology
SC Oncology
GA DQ0OH
UT WOS:000378898600002
PM 27349894
ER
PT J
AU Yang, BY
Hagberg, KW
Chen, J
Sahasrabuddhe, VV
Graubard, BI
Jick, S
McGlynn, KA
AF Yang, Baiyu
Hagberg, Katrina Wilcox
Chen, Jie
Sahasrabuddhe, Vikrant V.
Graubard, Barry I.
Jick, Susan
McGlynn, Katherine A.
TI Associations of antibiotic use with risk of primary liver cancer in the
Clinical Practice Research Datalink
SO BRITISH JOURNAL OF CANCER
LA English
DT Article
DE antibiotics; liver cancer; medical records database; case-control study
ID PRACTICE RESEARCH DATABASE; INFECTIONS; MICROBIOTA
AB Background: Use of antibiotics could alter human microbiota composition and decrease bacterial diversity. Such microbial dysbiosis may have implications in hepatocarcinogenesis; however, the association between antibiotic use and liver cancer risk has been minimally examined in humans.
Methods: We performed a nested case-control study (1195 primary liver cancer cases and 4640 matched controls) within the United Kingdom's Clinical Practice Research Datalink. Antibiotic use was obtained from prescription records. Multivariableadjusted odds ratio (OR) and 95% confidence interval (CI) were estimated using conditional logistic regression.
Results: Ever-use of prescription antibiotics was associated with a slightly increased risk of liver cancer, compared to non-use (OR = 1.22, 95% CI = 1.03 = 1.45). However, there was no clear dose-response relationship by the number of prescriptions or cumulative dose of antibiotic use, suggesting a non-causal association.
Conclusions: Our results do not support a role of antibiotic use in liver cancer development.
C1 [Yang, Baiyu; Chen, Jie; Sahasrabuddhe, Vikrant V.; Graubard, Barry I.; McGlynn, Katherine A.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Hagberg, Katrina Wilcox; Jick, Susan] Boston Collaborat Drug Surveillance Program, Lexington, MA 02421 USA.
[Hagberg, Katrina Wilcox; Jick, Susan] Boston Univ, Sch Publ Hlth, Lexington, MA 02421 USA.
[Sahasrabuddhe, Vikrant V.] NCI, Div Canc Prevent, Bethesda, MD 20892 USA.
RP Yang, BY (reprint author), NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
EM baiyu.yang@nih.gov
RI CPRD, CPRD/B-9594-2017
FU Intramural Research Program of the National Institutes of Health,
National Cancer Institute
FX This research was supported in part by the Intramural Research Program
of the National Institutes of Health, National Cancer Institute. We
thank Ms. Megan Braunlin for her help with the analyses.
NR 9
TC 0
Z9 0
U1 0
U2 2
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0007-0920
EI 1532-1827
J9 BRIT J CANCER
JI Br. J. Cancer
PD JUN 28
PY 2016
VL 115
IS 1
BP 85
EP 89
DI 10.1038/bjc.2016.148
PG 5
WC Oncology
SC Oncology
GA DQ0HR
UT WOS:000378880400013
PM 27219020
ER
PT J
AU Cannioto, RA
LaMonte, MJ
Kelemen, LE
Risch, HA
Eng, KH
Minlikeeva, AN
Hong, CC
Szender, JB
Sucheston-Campbell, L
Joseph, JM
Berchuck, A
Chang-Claude, J
Cramer, DW
DeFazio, A
Diergaarde, B
Dork, T
Doherty, JA
Edwards, RP
Fridley, BL
Friel, G
Goode, EL
Goodman, MT
Hillemanns, P
Hogdall, E
Hosono, S
Kelley, JL
Kjaer, SK
Klapdor, R
Matsuo, K
Odunsi, K
Nagle, CM
Olsen, CM
Paddock, LE
Pearce, CL
Pike, MC
Rossing, MA
Schmalfeldt, B
Segal, BH
Szamreta, EA
Thompson, PJ
Tseng, CC
Vierkant, R
Schildkraut, JM
Wentzensen, N
Wicklund, KG
Winham, SJ
Wu, AH
Modugno, F
Ness, RB
Jensen, A
Webb, PM
Terry, K
Bandera, EV
Moysich, KB
AF Cannioto, Rikki A.
LaMonte, Michael J.
Kelemen, Linda E.
Risch, Harvey A.
Eng, Kevin H.
Minlikeeva, Albina N.
Hong, Chi-Chen
Szender, J. Brian
Sucheston-Campbell, Lara
Joseph, Janine M.
Berchuck, Andrew
Chang-Claude, Jenny
Cramer, Daniel W.
DeFazio, Anna
Diergaarde, Brenda
Doerk, Thilo
Doherty, Jennifer A.
Edwards, Robert P.
Fridley, Brooke L.
Friel, Grace
Goode, Ellen L.
Goodman, Marc T.
Hillemanns, Peter
Hogdall, Estrid
Hosono, Satoyo
Kelley, Joseph L.
Kjaer, Susanne K.
Klapdor, Ruediger
Matsuo, Keitaro
Odunsi, Kunle
Nagle, Christina M.
Olsen, Catherine M.
Paddock, Lisa E.
Pearce, Celeste L.
Pike, Malcolm C.
Rossing, Mary A.
Schmalfeldt, Barbara
Segal, Brahm H.
Szamreta, Elizabeth A.
Thompson, Pamela J.
Tseng, Chiu-Chen
Vierkant, Robert
Schildkraut, Joellen M.
Wentzensen, Nicolas
Wicklund, Kristine G.
Winham, Stacey J.
Wu, Anna H.
Modugno, Francesmary
Ness, Roberta B.
Jensen, Allan
Webb, Penelope M.
Terry, Kathryn
Bandera, Elisa V.
Moysich, Kirsten B.
CA Australian Ovarian Canc Study Grp
TI Recreational physical inactivity and mortality in women with invasive
epithelial ovarian cancer: evidence from the Ovarian Cancer Association
Consortium
SO BRITISH JOURNAL OF CANCER
LA English
DT Article
DE recreational physical activity; inactivity; epithelial ovarian cancer;
mortality risk; survival
ID PROGNOSTIC-FACTORS; HORMONE-THERAPY; RISK; SURVIVAL; COHORT;
POLYMORPHISMS
AB Background: Little is known about modifiable behaviours that may be associated with epithelial ovarian cancer (EOC) survival. We conducted a pooled analysis of 12 studies from the Ovarian Cancer Association Consortium to investigate the association between pre-diagnostic physical inactivity and mortality.
Methods: Participants included 6806 women with a primary diagnosis of invasive EOC. In accordance with the Physical Activity Guidelines for Americans, women reporting no regular, weekly recreational physical activity were classified as inactive. We utilised Cox proportional hazard models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) representing the associations of inactivity with mortality censored at 5 years.
Results: In multivariate analysis, inactive women had significantly higher mortality risks, with (HR = 1.34, 95% CI: 1.18-1.52) and without (HR = 1.22, 95% CI: 1.12-1.33) further adjustment for residual disease, respectively.
Conclusion: In this large pooled analysis, lack of recreational physical activity was associated with increased mortality among women with invasive EOC.
C1 [Cannioto, Rikki A.; Minlikeeva, Albina N.; Hong, Chi-Chen; Sucheston-Campbell, Lara; Joseph, Janine M.; Moysich, Kirsten B.] Roswell Pk Canc Inst, Dept Canc Prevent & Control, Buffalo, NY 14263 USA.
[LaMonte, Michael J.; Minlikeeva, Albina N.] Univ Buffalo, Dept Epidemiol & Environm Hlth, Buffalo, NY USA.
[Kelemen, Linda E.] Med Univ S Carolina, Dept Publ Hlth Sci, Charleston, SC USA.
[Risch, Harvey A.] Yale Sch Publ Hlth, Dept Chron Dis Epidemiol, New Haven, CT USA.
[Eng, Kevin H.] Roswell Pk Canc Inst, Dept Biostat & Bioinformat, Buffalo, NY 14263 USA.
[Szender, J. Brian; Odunsi, Kunle] Roswell Pk Canc Inst, Dept Gynecol Oncol, Buffalo, NY 14263 USA.
[Berchuck, Andrew] Duke Univ, Med Ctr, Dept Obstet & Gynecol, Durham, NC 27710 USA.
[Chang-Claude, Jenny] German Canc Res Ctr, Div Canc Epidemiol, Unit Genet Epidemiol, Heidelberg, Germany.
[Chang-Claude, Jenny] Univ Med Ctr Hamburg Eppendorf, UCCH, Hamburg, Germany.
[Cramer, Daniel W.; Terry, Kathryn] Brigham & Womens Hosp, Obstet & Gynecol Epidemiol Ctr, 75 Francis St, Boston, MA 02115 USA.
[Cramer, Daniel W.; Terry, Kathryn] Harvard Med Sch, Boston, MA USA.
[DeFazio, Anna] Univ Sydney, Westmead Hosp, Dept Gynecol Oncol, Sydney, NSW, Australia.
[DeFazio, Anna] Univ Sydney, Westmead Inst Med Res, Sydney, NSW, Australia.
[Diergaarde, Brenda; Modugno, Francesmary] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA.
[Doerk, Thilo] Hannover Med Sch, Gynecol Res Unit, Hannover, Germany.
[Doherty, Jennifer A.] Dartmouth Med, Geisel Sch Med, Dept Epidemiol, Hanover, NH USA.
[Edwards, Robert P.; Kelley, Joseph L.; Modugno, Francesmary] Univ Pittsburgh, Sch Med, Dept Obstet Gynecol & Reprod Sci, Pittsburgh, PA USA.
[Edwards, Robert P.; Modugno, Francesmary] Magee Womens Res Inst, Ovarian Canc Ctr Excellence, Womens Canc Res Program, Pittsburgh, PA USA.
[Edwards, Robert P.; Modugno, Francesmary] Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA.
[Fridley, Brooke L.] Univ Kansas, Med Ctr, Biostat & Informat Shared Resource, Kansas City, KS 66103 USA.
[Friel, Grace] Independent Hlth, Buffalo, NY USA.
[Goode, Ellen L.] Mayo Clin, Div Epidemiol, Dept Hlth Sci Res, Rochester, MN USA.
[Goodman, Marc T.; Thompson, Pamela J.] Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Inst, Canc Prevent & Control, Los Angeles, CA 90048 USA.
[Hillemanns, Peter; Klapdor, Ruediger] Hannover Med Sch, Clin Gynaecol, Hannover, Germany.
[Hillemanns, Peter; Klapdor, Ruediger] Hannover Med Sch, Clin Obstet, Hannover, Germany.
[Hogdall, Estrid; Kjaer, Susanne K.; Jensen, Allan] Danish Canc Soc Res Ctr, Dept Virus Lifestyle & Genes, Copenhagen, Denmark.
[Hogdall, Estrid] Univ Copenhagen, Herlev Hosp, Dept Pathol, Mol Unit, Copenhagen, Denmark.
[Hosono, Satoyo] Aichi Canc Ctr Res Inst, Div Epidemiol & Prevent, Nagoya, Aichi, Japan.
[Kjaer, Susanne K.] Univ Copenhagen, Rigshosp, Dept Gynaecol, Copenhagen, Denmark.
[Matsuo, Keitaro] Aichi Canc Ctr Res Inst, Div Mol Med, Nagoya, Aichi, Japan.
[Nagle, Christina M.; Olsen, Catherine M.; Webb, Penelope M.] QIMR Berghofer Med Res Inst, Populat Hlth Dept, Brisbane, Qld, Australia.
[Paddock, Lisa E.] Rutgers Canc Inst New Jersey, New Jersey State Canc Registry, New Brunswick, NJ USA.
[Pearce, Celeste L.] Univ Michigan, Dept Epidemiol, Ann Arbor, MI 48109 USA.
[Pike, Malcolm C.] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA.
[Rossing, Mary A.; Wicklund, Kristine G.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Program Epidemiol, 1124 Columbia St, Seattle, WA 98104 USA.
[Schmalfeldt, Barbara] Univ Med Ctr Hamburg Eppendorf UKE, Dept Gynecol, Hamburg, Germany.
[Segal, Brahm H.] Roswell Pk Canc Inst, Dept Immunol, Buffalo, NY 14263 USA.
[Segal, Brahm H.] Roswell Pk Canc Inst, Dept Med, Buffalo, NY 14263 USA.
[Szamreta, Elizabeth A.; Bandera, Elisa V.] Rutgers Canc Inst New Jersey, Canc Prevent & Control, New Brunswick, NJ USA.
[Tseng, Chiu-Chen; Wu, Anna H.] Univ Southern Calif, Norris Comprehens Canc Ctr, Keck Sch Med, Dept Prevent Med, Los Angeles, CA USA.
[Vierkant, Robert; Winham, Stacey J.] Mayo Clin, Div Biomed Stat & Informat, Dept Hlth Sci Res, Rochester, MN USA.
[Schildkraut, Joellen M.] Univ Virginia, Sch Med, Dept Publ Hlth Sci, Charlottesville, VA 22908 USA.
[Wentzensen, Nicolas] NCI, Div Canc Epidemiol & Genet, Clin Genet Branch, Bethesda, MD 20892 USA.
[Ness, Roberta B.] Univ Texas Sch Publ Hlth, Houston, TX USA.
RP Moysich, KB (reprint author), Roswell Pk Canc Inst, Dept Canc Prevent & Control, Buffalo, NY 14263 USA.
EM Kirsten.moysich@roswellpark.org
RI Olsen, Catherine/C-8785-2009; Dork, Thilo/J-8620-2012;
OI Olsen, Catherine/0000-0003-4483-1888; Matsuo,
Keitaro/0000-0003-1761-6314; Winham, Stacey/0000-0002-8492-9102
FU NIH/NCI [R01CA095023, R01CA126841]; Roswell Park Alliance Foundation;
Interdisciplinary Training Grant in Cancer Epidemiology [R25CA113951];
U.S. Army Medical Research and Materiel Command [DAMD17-01-1-0729];
National Health & Medical Research Council of Australia; Cancer Councils
of New South Wales, Victoria, Queensland, South Australia and Tasmania;
Cancer Foundation of Western Australia; National Health and Medical
Research Council of Australia [199600, 400281]; National Institutes of
Health [R01-CA074850, R01-CA080742, R01-CA112523, R01-CA87538,
R01-CA122443, P30-CA15083, P50-CA136393, R01-CA54419, P50-CA105009];
U.S. National Institutes of Health [R01-CA58598, N01-CN-55424,
N01-PC-67001]; Ministry of Health, Labour and Welfare; National Cancer
Institute, Bethesda, MD [R01-CA61107]; Danish Cancer Society,
Copenhagen, Denmark [94 222 52]; Mermaid I project; Mayo Foundation;
Minnesota Ovarian Cancer Alliance; Fred C. and Katherine B. Andersen
Foundation; Department of Defense [W81XWH-10-1-02802]; National Cancer
Institute [NIH-K07 CA095666, R01-CA83918, NIH-K22-CA138563,
P30-CA072720]; Cancer Institute of New Jersey; NCI CCSG award
[P30-CA008748]; California Cancer Research Program [00-01389V-20170,
2II0200]; [5T32CA108456]; [R01 CA188900]; [DOD: DAMD17-02-1-0669];
[NCI: K07-CA080668]; [R01-CA95023]; [P50-CA159981]; [R01-CA126841];
[P01CA17054]; [P30CA14089]; [R01CA61132]; [N01PC67010];
[R03CA113148]; [R03CA115195]; [N01CN025403]
FX KBM is supported by NIH/NCI R01CA095023 and NIH/NCI R01CA126841; KHE and
KBM were supported by the Roswell Park Alliance Foundation; JBS was
supported by 5T32CA108456; ANM was supported by Interdisciplinary
Training Grant in Cancer Epidemiology R25CA113951; BHS was supported by
R01 CA188900; AUS was supported by the U.S. Army Medical Research and
Materiel Command (DAMD17-01-1-0729), National Health & Medical Research
Council of Australia, Cancer Councils of New South Wales, Victoria,
Queensland, South Australia and Tasmania, Cancer Foundation of Western
Australia; National Health and Medical Research Council of Australia
(199600 and 400281); CON was supported by National Institutes of Health
(R01-CA074850; R01-CA080742); DOV was supported by National Institutes
of Health R01-CA112523 and R01-CA87538; HAW was supported by U.S.
National Institutes of Health (R01-CA58598, N01-CN-55424 and
N01-PC-67001); HOP was supported by DOD: DAMD17-02-1-0669 and NCI:
K07-CA080668, R01-CA95023, P50-CA159981, R01-CA126841; JPN was supported
by Grant-in-Aid for the Third Term Comprehensive 10-Year Strategy for
Cancer Control from the Ministry of Health, Labour and Welfare; MAC was
supported by National Institutes of Health (R01-CA122443, P30-CA15083,
P50-CA136393); MAL was supported by research grant R01-CA61107 from the
National Cancer Institute, Bethesda, MD; research grant 94 222 52 from
the Danish Cancer Society, Copenhagen, Denmark; and the Mermaid I
project; MAY was supported by National Institutes of Health
(R01-CA122443, P30-CA15083, P50-CA136393); Mayo Foundation; Minnesota
Ovarian Cancer Alliance; Fred C. and Katherine B. Andersen Foundation;
NEC was supported by National Institutes of Health R01-CA54419 and
P50-CA105009 and Department of Defense W81XWH-10-1-02802; NJO was
supported by National Cancer Institute (NIH-K07 CA095666, R01-CA83918,
NIH-K22-CA138563, and P30-CA072720) and the Cancer Institute of New
Jersey and NCI CCSG award (P30-CA008748); USC was supported by
P01CA17054, P30CA14089, R01CA61132, N01PC67010, R03CA113148,
R03CA115195, N01CN025403, and California Cancer Research Program
(00-01389V-20170, 2II0200).
NR 34
TC 0
Z9 0
U1 1
U2 2
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0007-0920
EI 1532-1827
J9 BRIT J CANCER
JI Br. J. Cancer
PD JUN 28
PY 2016
VL 115
IS 1
BP 95
EP 101
DI 10.1038/bjc.2016.153
PG 7
WC Oncology
SC Oncology
GA DQ0HR
UT WOS:000378880400015
PM 27299959
ER
PT J
AU Malachowa, N
Kobayashi, SD
Quinn, MT
DeLeo, FR
AF Malachowa, Natalia
Kobayashi, Scott D.
Quinn, Mark T.
DeLeo, Frank R.
TI NET Confusion
SO FRONTIERS IN IMMUNOLOGY
LA English
DT Article
DE host defense; extracellular trap; inflammation; inflammatory disorder;
neutrophil
ID NEUTROPHIL EXTRACELLULAR TRAPS; RECOMBINANT HUMAN DEOXYRIBONUCLEASE;
MONOCYTE-DERIVED MACROPHAGES; PANTON-VALENTINE LEUKOCIDIN; PROGRAMMED
CELL-DEATH; STAPHYLOCOCCUS-AUREUS; CYSTIC-FIBROSIS; DNA TRAPS; IN-VIVO;
POLYMORPHONUCLEAR LEUKOCYTES
AB Neutrophils are arguably the most important white blood cell for defense against bacterial and fungal infections. These leukocytes are produced in high numbers on a daily basis in humans and are recruited rapidly to injured/infected tissues. Phagocytosis and subsequent intraphagosomal killing and digestion of microbes have historically been the accepted means by which neutrophils carry out their role in innate host defense. Indeed, neutrophils contain and produce numerous cytotoxic molecules, including antimicrobial peptides, proteases, and reactive oxygen species, that are highly effective at killing the vast majority of ingested microbes. On the other hand, it is these characteristics - high numbers and toxicity - that endow neutrophils with the potential to injure and destroy host tissues. This potential is borne out by many inflammatory processes and diseases. Therefore, it is not surprising that host mechanisms exist to control virtually all steps in the neutrophil activation process and to prevent unintended neutrophil activation and/or lysis during the resolution of inflammatory responses or during steady-state turnover. The notion that neutrophil extracellular traps (NETs) form by cytolysis as a standard host defense mechanism seems inconsistent with these aforementioned neutrophil "containment" processes. It is with this caveat in mind that we provide perspective on the role of NETs in human host defense and disease.
C1 [Malachowa, Natalia; Kobayashi, Scott D.; DeLeo, Frank R.] NIAID, Rocky Mt Lab, Bacteriol Lab, NIH, Hamilton, MT 59840 USA.
[Quinn, Mark T.] Montana State Univ, Dept Microbiol & Immunol, Bozeman, MT 59717 USA.
RP DeLeo, FR (reprint author), NIAID, Rocky Mt Lab, Bacteriol Lab, NIH, Hamilton, MT 59840 USA.
EM fdeleo@niaid.nih.gov
FU National Institute of Allergy and Infectious Diseases, National
Institutes of Health; National Institutes of Health IDeA Program COBRE
grant [GM110732]; USDA National Institute of Food and Agriculture Hatch
project [1009546]; Montana State University Agricultural Experiment
Station
FX NM, SK, and FD are supported by the Intramural Research Program of the
National Institute of Allergy and Infectious Diseases, National
Institutes of Health. MQ is supported by National Institutes of Health
IDeA Program COBRE grant GM110732; USDA National Institute of Food and
Agriculture Hatch project 1009546; and the Montana State University
Agricultural Experiment Station.
NR 132
TC 2
Z9 2
U1 3
U2 7
PU FRONTIERS MEDIA SA
PI LAUSANNE
PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015,
SWITZERLAND
SN 1664-3224
J9 FRONT IMMUNOL
JI Front. Immunol.
PD JUN 28
PY 2016
VL 7
AR 259
DI 10.3389/fimmu.2015.00259
PG 10
WC Immunology
SC Immunology
GA DP6DH
UT WOS:000378586600001
PM 27446089
ER
PT J
AU Wang, JY
Huang, YN
Chiu, CC
Tweedie, D
Luo, WM
Pick, CG
Chou, SY
Luo, Y
Hoffer, BJ
Greig, NH
Wang, JY
AF Wang, Jin-Ya
Huang, Ya-Ni
Chiu, Chong-Chi
Tweedie, David
Luo, Weiming
Pick, Chaim G.
Chou, Szu-Yi
Luo, Yu
Hoffer, Barry J.
Greig, Nigel H.
Wang, Jia-Yi
TI Pomalidomide mitigates neuronal loss, neuroinflammation, and behavioral
impairments induced by traumatic brain injury in rat
SO JOURNAL OF NEUROINFLAMMATION
LA English
DT Article
DE Pomalidomide; Thalidomide; Traumatic brain injury; Controlled cortical
impact; Tumor necrosis factor-alpha; Interleukin-1 beta; Interleukin-6;
Glutamate excitotoxicity; Neuronal apoptosis; Neuroinflammation
ID TUMOR-NECROSIS-FACTOR; CENTRAL-NERVOUS-SYSTEM; CLOSED-HEAD INJURY;
CONTROLLED CORTICAL IMPACT; ALPHA SYNTHESIS INHIBITOR; TNF-ALPHA;
IN-VITRO; INFLAMMATORY CYTOKINES; FUNCTIONAL OUTCOMES; COGNITIVE
DEFICITS
AB Background: Traumatic brain injury (TBI) is a global health concern that typically causes emotional disturbances and cognitive dysfunction. Secondary pathologies following TBI may be associated with chronic neurodegenerative disorders and an enhanced likelihood of developing dementia-like disease in later life. There are currently no approved drugs for mitigating the acute or chronic effects of TBI.
Methods: The effects of the drug pomalidomide (Pom), an FDA-approved immunomodulatory agent, were evaluated in a rat model of moderate to severe TBI induced by controlled cortical impact. Post-TBI intravenous administration of Pom (0.5 mg/kg at 5 or 7 h and 0.1 mg/kg at 5 h) was evaluated on functional and histological measures that included motor function, fine more coordination, somatosensory function, lesion volume, cortical neurodegeneration, neuronal apoptosis, and the induction of pro-inflammatory cytokines (TNF-alpha, IL-1 beta, IL-6).
Results: Pom 0.5 mg/kg administration at 5 h, but not at 7 h post-TBI, significantly mitigated the TBI-induced injury volume and functional impairments, neurodegeneration, neuronal apoptosis, and cytokine mRNA and protein induction. To evaluate underlying mechanisms, the actions of Pom on neuronal survival, microglial activation, and the induction of TNF-alpha were assessed in mixed cortical cultures following a glutamate challenge. Pom dose-dependently ameliorated glutamate-mediated cytotoxic effects on cell viability and reduced microglial cell activation, significantly attenuating the induction of TNF-alpha.
Conclusions: Post-injury treatment with a single Pom dose within 5 h significantly reduced functional impairments in a well-characterized animal model of TBI. Pom decreased the injury lesion volume, augmented neuronal survival, and provided anti-inflammatory properties. These findings strongly support the further evaluation and optimization of Pom for potential use in clinical TBI.
C1 [Tweedie, David; Luo, Weiming; Greig, Nigel H.] NIA, Drug Design & Dev Sect, Translat Gerontol Branch, Intramural Res Program,NIH, Baltimore, MD 21224 USA.
[Wang, Jin-Ya; Huang, Ya-Ni; Wang, Jia-Yi] Taipei Med Univ, Coll Med, Grad Inst Med Sci, 250 Wu Hsing St, Taipei 110, Taiwan.
[Huang, Ya-Ni] Hsin Sheng Jr Coll Med Care & Management, Dept Nursing, Taoyuan, Taiwan.
[Chiu, Chong-Chi] Chi Mei Med Ctr, Dept Gen Surg, Tainan, Taiwan.
[Chiu, Chong-Chi] Chi Mei Med Ctr, Dept Gen Surg, Liouying, Taiwan.
[Pick, Chaim G.] Tel Aviv Univ, Dept Anat & Anthropol, Sackler Sch Med, Tel Aviv, Israel.
[Pick, Chaim G.] Tel Aviv Univ, Sagol Sch Neurosci, Tel Aviv, Israel.
[Chou, Szu-Yi] Taipei Med Univ, Coll Med Sci & Technol, Grad Program Neuroregenerat, Taipei, Taiwan.
[Luo, Yu; Hoffer, Barry J.] Case Western Reserve Univ, Sch Med, Dept Neurosurg, Cleveland, OH 44106 USA.
[Wang, Jia-Yi] Taipei Med Univ, Coll Med, Dept Physiol, 250 Wu Hsing St, Taipei 110, Taiwan.
RP Greig, NH (reprint author), NIA, Drug Design & Dev Sect, Translat Gerontol Branch, Intramural Res Program,NIH, Baltimore, MD 21224 USA.; Wang, JY (reprint author), Taipei Med Univ, Coll Med, Grad Inst Med Sci, 250 Wu Hsing St, Taipei 110, Taiwan.; Wang, JY (reprint author), Taipei Med Univ, Coll Med, Dept Physiol, 250 Wu Hsing St, Taipei 110, Taiwan.
EM greign@mail.NIH.gov; jywang2010@tmu.edu.tw
FU Ministry of Science and Technology, Taiwan [MOST104-2923-B-038-001-MY3];
Ari and Regine Aprijaskis Fund at Tel-Aviv University, Tel-Aviv, Israel;
National Institute of Neurological Disorders and Stroke, NIH
[RO1NS094152]; Intramural Research Program of the National Institute on
Aging, NIH [AG 000311-16]
FX This study was supported in part by (i) a grant from the Ministry of
Science and Technology, Taiwan (MOST104-2923-B-038-001-MY3); (ii) the
Ari and Regine Aprijaskis Fund at Tel-Aviv University, Tel-Aviv, Israel;
(iii) the National Institute of Neurological Disorders and Stroke, NIH
(grant RO1NS094152); and (iv) the Intramural Research Program of the
National Institute on Aging, NIH (AG 000311-16). These funding
organizations had no role in the design of the study or the collection,
analysis, and interpretation of data and in writing the manuscript.
NR 89
TC 1
Z9 1
U1 2
U2 3
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1742-2094
J9 J NEUROINFLAMM
JI J. Neuroinflamm.
PD JUN 28
PY 2016
VL 13
AR 168
DI 10.1186/s12974-016-0631-6
PG 17
WC Immunology; Neurosciences
SC Immunology; Neurosciences & Neurology
GA DQ0BZ
UT WOS:000378864100002
PM 27353053
ER
PT J
AU Lustig, A
Shterev, I
Geyer, S
Shi, A
Hu, YQ
Morishita, Y
Nagamura, H
Sasaki, K
Maki, M
Hayashi, I
Furukawa, K
Yoshida, K
Kajimura, J
Kyoizumi, S
Kusunoki, Y
Ohishi, W
Nakachi, K
Weng, NP
Hayashi, T
AF Lustig, Ana
Shterev, Ivo
Geyer, Susan
Shi, Alvin
Hu, Yiqun
Morishita, Yukari
Nagamura, Hiroko
Sasaki, Keiko
Maki, Mayumi
Hayashi, Ikue
Furukawa, Kyoji
Yoshida, Kengo
Kajimura, Junko
Kyoizumi, Seishi
Kusunoki, Yoichiro
Ohishi, Waka
Nakachi, Kei
Weng, Nan-ping
Hayashi, Tomonori
TI Long term effects of radiation exposure on telomere lengths of
leukocytes and its associated biomarkers among atomic-bomb survivors
SO ONCOTARGET
LA English
DT Article
DE Ionizing radiation; telomeres; leukocytes; aging; Hiroshima; Gerotarget
ID FALSE DISCOVERY RATE; IONIZING-RADIATION; BLOOD-LYMPHOCYTES; DNA-DAMAGE;
IN-VIVO; AGE; SENESCENCE; CELL; SENSITIVITY; MARKERS
AB Ionizing radiation (IR) is a major source of cellular damage and the immediate cellular response to IR has been well characterized. But the long-term impact of IR on cell function and its relationship with aging are not known. Here, we examined the IR effects on telomere length and other biomarkers 50 to 68 years post-exposure (two time points per person) in survivors of the atomic bombing at Hiroshima during WWII. We found that telomere length of leukocytes was inversely correlated with the dose of IR (p=0.008), and this effect was primarily found in survivors who were exposed at younger ages; specifically those <12 years old (p=0.0004). Although a dose-related retardation of telomere shortening with age was observed in the cross-sectional data, longitudinal follow-up after 11 years did not show IR exposure-related alteration of the rate of telomere shortening with age. In addition, IR diminished the associations between telomere length and selected aging biomarkers that were observed in survivors with no dose. These included uric acid metabolism, cytokines, and blood T cell counts. These findings showed long-lasting detrimental effects of IR on telomere length of leukocytes in both dose- and age-at-exposure dependent manner, and on alterations of biomarkers with aging.
C1 [Lustig, Ana; Shi, Alvin; Weng, Nan-ping] NIA, Lab Mol Biol & Immunol, NIH, Baltimore, MD 21224 USA.
[Shterev, Ivo] Duke Univ, Durham, NC USA.
[Geyer, Susan] Univ S Florida, Hlth Informat Inst, Tampa, FL USA.
[Hu, Yiqun; Morishita, Yukari; Nagamura, Hiroko; Sasaki, Keiko; Maki, Mayumi; Yoshida, Kengo; Kajimura, Junko; Kyoizumi, Seishi; Kusunoki, Yoichiro; Nakachi, Kei; Hayashi, Tomonori] Radiat Effects Res Fdn RERF, Dept Radiobiol Mol Epidemiol, Hiroshima, Japan.
[Hayashi, Ikue] Hiroshima Univ, Fac Dent, Cent Res Lab, Hiroshima, Japan.
[Furukawa, Kyoji] RERF, Dept Stat, Hiroshima, Japan.
[Ohishi, Waka] RERF, Dept Clin Studies, Hiroshima, Japan.
RP Weng, NP (reprint author), NIA, Lab Mol Biol & Immunol, NIH, Baltimore, MD 21224 USA.; Hayashi, T (reprint author), Radiat Effects Res Fdn RERF, Dept Radiobiol Mol Epidemiol, Hiroshima, Japan.
EM wengn@mail.nih.gov; tomo@rerf.or.jp
FU Radiation and Nuclear Countermeasures Program of the National Institute
of Allergy and Infectious Diseases (NIAID); National Institute on Aging,
National Institutes of Health (NIH)
FX We thank Richard Hatchett for his comments and suggestions. This study
is supported by the Radiation and Nuclear Countermeasures Program of the
National Institute of Allergy and Infectious Diseases (NIAID), and the
Intramural Research Program of the National Institute on Aging, National
Institutes of Health (NIH).
NR 33
TC 1
Z9 1
U1 3
U2 3
PU IMPACT JOURNALS LLC
PI ALBANY
PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA
SN 1949-2553
J9 ONCOTARGET
JI Oncotarget
PD JUN 28
PY 2016
VL 7
IS 26
BP 38988
EP 38998
DI 10.18632/oncotarget.8801
PG 11
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA DP6NV
UT WOS:000378614700002
PM 27102155
ER
PT J
AU Di Germanio, C
Bernier, M
Petr, M
Mattioli, M
Barboni, B
de Cabo, R
AF Di Germanio, Clara
Bernier, Michel
Petr, Michael
Mattioli, Mauro
Barboni, Barbara
de Cabo, Rafael
TI Conditioned medium derived from rat amniotic epithelial cells confers
protection against inflammation, cancer, and senescence
SO ONCOTARGET
LA English
DT Article
DE amniotic epithelial cells; inflammation; tumorigenesis; senescence;
SASP; Gerotarget
ID STEM-CELLS; SECRETORY PHENOTYPE; CELLULAR SENESCENCE; HUMAN FIBROBLASTS;
IN-VITRO; MEMBRANE; DIFFERENTIATION; POLARIZATION; PLACENTA;
TRANSPLANTATION
AB Amniotic epithelial cells (AECs) are a class of fetal stem cells that derives from the epiblast and resides in the amnion until birth. AECs are suitable candidates for regenerative medicine because of the ease of collection, their low immunogenicity and inability to form tumors after transplantation. Even though human AECs have been widely investigated, the fact remains that very little is known about AECs isolated from rat, one of the most common animal models in medical testing. In this study, we showed that rat AECs retained stemness properties and plasticity, expressed the pluripotency markers Sox2, Nanog, and Oct4 and were able to differentiate toward the osteogenic lineage. The addition of conditioned medium collected from rat AECs to lipopolysaccharide-activated macrophages elicited anti-inflammatory properties through a decrease of Tnfa expression and slowed tumor cell proliferation in vitro and in vivo. The senescence-associated secretory phenotype was also significantly lower upon incubation of senescent human IMR-90 fibroblast cells with conditioned medium from rat AECs. These results confirm the potential of AECs in the modulation of inflammatory mechanisms and open new therapeutic possibilities for regenerative medicine and anti-aging therapies as well.
C1 [Di Germanio, Clara; Mattioli, Mauro; Barboni, Barbara] Univ Teramo, Fac Vet Med, Teramo, Italy.
[Di Germanio, Clara; Bernier, Michel; Petr, Michael; de Cabo, Rafael] NIA, Translat Gerontol Branch, NIH, Baltimore, MD 21224 USA.
[Mattioli, Mauro] Ist Zooprofilatt Sperimentale Abruzzo & Molise G, Teramo, Italy.
RP Barboni, B (reprint author), Univ Teramo, Fac Vet Med, Teramo, Italy.; de Cabo, R (reprint author), NIA, Translat Gerontol Branch, NIH, Baltimore, MD 21224 USA.
EM bbarboni@unite.it; decabora@grc.nia.nih.gov
FU National Institute on Aging, National Institutes of Health; Fatro
S.p.A.; PRIN
FX This work was supported by the Intramural Research Program of the
National Institute on Aging, National Institutes of Health (MB and RdC)
and funding from Fatro S.p.A. 2014 (MM). This work had also the
financial support of PRIN 2010-11 "Cellule staminali e scaffold 3D: un
biocomplesso innovativo nella rigenerazione ossea" (BB).
NR 67
TC 0
Z9 0
U1 5
U2 6
PU IMPACT JOURNALS LLC
PI ALBANY
PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA
SN 1949-2553
J9 ONCOTARGET
JI Oncotarget
PD JUN 28
PY 2016
VL 7
IS 26
BP 39051
EP 39064
DI 10.18632/oncotarget.9694
PG 14
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA DP6NV
UT WOS:000378614700007
PM 27259996
ER
PT J
AU Wang, DR
Narula, N
Azzopardi, S
Smith, RS
Nasar, A
Altorki, NK
Mittal, V
Somwar, R
Stiles, BM
Du, YCN
AF Wang, Dunrui
Narula, Navneet
Azzopardi, Stephanie
Smith, Roger S.
Nasar, Abu
Altorki, Nasser K.
Mittal, Vivek
Somwar, Romel
Stiles, Brendon M.
Du, Yi-Chieh Nancy
TI Expression of the receptor for hyaluronic acid mediated motility (RHAMM)
is associated with poor prognosis and metastasis in non-small cell lung
carcinoma
SO ONCOTARGET
LA English
DT Article
DE lung cancer; receptor for hyaluronic acid-mediated motility; metastasis;
prognosis
ID BREAST-CANCER; TUMOR PROGRESSION; MUTATIONS; PROTEIN; GEFITINIB;
PROLIFERATION; SURVIVAL; THERAPY; DISEASE; CD168
AB The receptor for hyaluronic acid-mediated motility (RHAMM) is upregulated in various cancers, but its role in primary and metastatic non-small cell lung carcinoma (NSCLC) remains to be determined. Here, we investigate the clinical relevance of RHAMM expression in NSCLC. RHAMM protein expression correlates with histological differentiation stages and extent of the primary tumor (T stages) in 156 patients with primary NSCLC. Importantly, while focal RHAMM staining pattern is present in 57% of primary NSCLC, intense RHAMM protein expression is present in 96% of metastatic NSCLC cases. In a publicly available database, The Cancer Genome Atlas (TCGA), RHAMM mRNA expression is 12- and 10-fold higher in lung adenocarcinoma and squamous lung carcinoma than in matched normal lung tissues, respectively. RHAMM mRNA expression correlates with stages of differentiation and inferior survival in more than 400 cases of lung adenocarcinoma in the Director's Challenge cohort. Of 4 RHAMM splice variants, RHAMMv3 (also known as RHAMM(B)) is the dominant variant in NSCLC. Moreover, shRNA-mediated knockdown of RHAMM reduced the migratory ability of two lung adenocarcinoma cell lines, H1975 and H3255. Taken together, RHAMM, most likely RHAMMv3 (RHAMM(B)), can serve as a prognostic factor for lung adenocarcinomas and a potential therapeutic target in NSCLC to inhibit tumor migration.
C1 [Wang, Dunrui] NCI, Cellular Oncol Lab, NIH, Bethesda, MD 20892 USA.
[Narula, Navneet; Azzopardi, Stephanie; Du, Yi-Chieh Nancy] Weill Cornell Med, Dept Pathol & Lab Med, New York, NY 10065 USA.
[Smith, Roger S.; Somwar, Romel] Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, New York, NY 10065 USA.
[Nasar, Abu; Altorki, Nasser K.; Mittal, Vivek; Stiles, Brendon M.] Weill Cornell Med, Dept Cardiothorac Surg, New York, NY 10065 USA.
RP Du, YCN (reprint author), Weill Cornell Med, Dept Pathol & Lab Med, New York, NY 10065 USA.
EM nad2012@med.cornell.edu
FU DOD [W81XWH-13-1-0331]; NIH [1R21CA173348-01A1]
FX This work is partially supported by DOD grant W81XWH-13-1-0331 and NIH
grant 1R21CA173348-01A1 (to Y.-C.N.D.).
NR 42
TC 0
Z9 0
U1 1
U2 1
PU IMPACT JOURNALS LLC
PI ALBANY
PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA
SN 1949-2553
J9 ONCOTARGET
JI Oncotarget
PD JUN 28
PY 2016
VL 7
IS 26
BP 39957
EP 39969
DI 10.18632/oncotarget.9554
PG 13
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA DP6NV
UT WOS:000378614700078
PM 27220886
ER
PT J
AU Bullova, P
Cougnoux, A
Abunimer, L
Kopacek, J
Pastorekova, S
Pacak, K
AF Bullova, Petra
Cougnoux, Antony
Abunimer, Luma
Kopacek, Juraj
Pastorekova, Silvia
Pacak, Karel
TI Hypoxia potentiates the cytotoxic effect of piperlongumine in
pheochromocytoma models
SO ONCOTARGET
LA English
DT Article
DE pheochromocytoma; piperlongumine; hypoxia; reactive-oxygen species;
apoptosis
ID PROTEASOME INHIBITOR BORTEZOMIB; CANCER-CELL-DEATH;
HEPATOCELLULAR-CARCINOMA; MESENCHYMAL TRANSITION; DEPENDENT APOPTOSIS;
AUTOPHAGY; ACTIVATION; ROS; PARAGANGLIOMAS; NECROPTOSIS
AB Hypoxia is a common feature of solid tumors that activates a plethora of pathways, resulting in proliferation and resistance of cancer cells to radio-and chemotherapy. Pheochromocytomas/paragangliomas (PHEOs/PGLs) with mutations in the gene coding for the subunit B of succinate dehydrogenase (SDHB) are the most aggressive forms of the disease, which is partially due to their pseudohypoxic character, metabolic abnormalities, and elevated reactive oxygen species (ROS) levels. We investigated the effect of piperlongumine (PL), a natural product with cytotoxic properties restricted to cancer cells by significantly increasing intracellular ROS levels, on PHEO cells. Here we report for the first time that PL mediates PHEO cell death by activating both apoptosis and necroptosis in vitro and in vivo. This effect is magnified in hypoxic conditions, making PL a promising potential candidate for use as a therapeutic option for patients with PHEO/PGL, including those with SDHB mutations.
C1 [Bullova, Petra; Abunimer, Luma; Pacak, Karel] Eunice Kennedy Shriver NICHD, Sect Med Neuroendocrinol, NIH, Bethesda, MD 20892 USA.
[Bullova, Petra; Kopacek, Juraj; Pastorekova, Silvia] Slovak Acad Sci, Dept Mol Med, Inst Virol, Biomed Res Ctr, Bratislava 84505, Slovakia.
[Cougnoux, Antony] Eunice Kennedy Shriver NICHD, Sect Mol Dysmorphol, NIH, Bethesda, MD 20892 USA.
RP Pacak, K (reprint author), Eunice Kennedy Shriver NICHD, Sect Med Neuroendocrinol, NIH, Bethesda, MD 20892 USA.
EM karel@mail.nih.gov
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development, NIH
FX This work was supported by the Intramural Research Program of the Eunice
Kennedy Shriver National Institute of Child Health and Human
Development, NIH.
NR 59
TC 0
Z9 0
U1 4
U2 6
PU IMPACT JOURNALS LLC
PI ALBANY
PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA
SN 1949-2553
J9 ONCOTARGET
JI Oncotarget
PD JUN 28
PY 2016
VL 7
IS 26
BP 40531
EP 40545
DI 10.18632/oncotarget.9643
PG 15
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA DP6NV
UT WOS:000378614700120
PM 27244895
ER
PT J
AU Williamson, JD
Supiano, MA
Applegate, WB
Berlowitz, DR
Campbell, RC
Chertow, GM
Fine, LJ
Haley, WE
Hawfield, AT
Ix, JH
Kitzman, D
Kostis, JB
Krousel-Wood, MA
Launer, LJ
Oparil, S
Rodriguez, CJ
Roumie, CL
Shorr, RI
Sink, KM
Wadley, VG
Whelton, PK
Whittle, J
Woolard, NF
Wright, JT
Pajewski, NM
AF Williamson, Jeff D.
Supiano, Mark A.
Applegate, William B.
Berlowitz, Dan R.
Campbell, Ruth C.
Chertow, Glenn M.
Fine, Larry J.
Haley, William E.
Hawfield, Amret T.
Ix, Joachim H.
Kitzman, DalaneW.
Kostis, John B.
Krousel-Wood, Marie A.
Launer, Lenore J.
Oparil, Suzanne
Rodriguez, Carlos J.
Roumie, Christianne L.
Shorr, Ronald I.
Sink, Kaycee M.
Wadley, Virginia G.
Whelton, Paul K.
Whittle, Jeffrey
Woolard, Nancy F.
Wright, Jackson T., Jr.
Pajewski, Nicholas M.
CA SPRINT Res Grp
TI Intensive vs Standard Blood Pressure Control and Cardiovascular Disease
Outcomes in Adults Aged >= 75 Years A Randomized Clinical Trial
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Article
ID ANTIHYPERTENSIVE TREATMENT; INTERVENTION TRIAL; ELDERLY POPULATION;
OLDER-PEOPLE; HYPERTENSION; FRAILTY; STROKE; RISK; DISABILITY;
GUIDELINES
AB IMPORTANCE The appropriate treatment target for systolic blood pressure (SBP) in older patients with hypertension remains uncertain.
OBJECTIVE To evaluate the effects of intensive (<120mmHg) compared with standard (<140mmHg) SBP targets in persons aged 75 years or older with hypertension but without diabetes.
DESIGN, SETTING, AND PARTICIPANTS A multicenter, randomized clinical trial of patients aged 75 years or older who participated in the Systolic Blood Pressure Intervention Trial (SPRINT). Recruitment began on October 20, 2010, and follow-up ended on August 20, 2015.
INTERVENTIONS Participants were randomized to an SBP target of less than 120mmHg (intensive treatment group, n = 1317) or an SBP target of less than 140mmHg (standard treatment group, n = 1319).
MAIN OUTCOMES AND MEASURES The primary cardiovascular disease outcomewas a composite of nonfatalmyocardial infarction, acute coronary syndrome not resulting in a myocardial infarction, nonfatal stroke, nonfatal acute decompensated heart failure, and death from cardiovascular causes. All-cause mortality was a secondary outcome.
RESULTS Among 2636 participants (mean age, 79.9 years; 37.9% women), 2510 (95.2%) provided complete follow-up data. At a median follow-up of 3.14 years, there was a significantly lower rate of the primary composite outcome (102 events in the intensive treatment group vs 148 events in the standard treatment group; hazard ratio [HR], 0.66 [95% CI, 0.51-0.85]) and all-cause mortality (73 deaths vs 107 deaths, respectively; HR, 0.67 [95% CI, 0.49-0.91]). The overall rate of serious adverse events was not different between treatment groups (48.4% in the intensive treatment group vs 48.3% in the standard treatment group; HR, 0.99 [95% CI, 0.89-1.11]). Absolute rates of hypotension were 2.4% in the intensive treatment group vs 1.4% in the standard treatment group (HR, 1.71 [95% CI, 0.97-3.09]), 3.0% vs 2.4%, respectively, for syncope (HR, 1.23 [95% CI, 0.76-2.00]), 4.0% vs 2.7% for electrolyte abnormalities (HR, 1.51 [95% CI, 0.99-2.33]), 5.5% vs 4.0% for acute kidney injury (HR, 1.41 [95% CI, 0.98-2.04]), and 4.9% vs 5.5% for injurious falls (HR, 0.91 [95% CI, 0.65-1.29]).
CONCLUSIONS AND RELEVANCE Among ambulatory adults aged 75 years or older, treating to an SBP target of less than 120mmHg compared with an SBP target of less than 140mmHg resulted in significantly lower rates of fatal and nonfatal major cardiovascular events and death from any cause.
C1 [Williamson, Jeff D.; Applegate, William B.; Sink, Kaycee M.; Woolard, Nancy F.] Wake Forest Sch Med, Med Ctr Blvd, Sect Gerontol & Geriatr Med, Winston Salem, NC 27157 USA.
[Supiano, Mark A.] Univ Utah, Sch Med, Div Geriatr, Salt Lake City, UT USA.
[Supiano, Mark A.] Vet Affairs Salt Lake City, Geriatr Res Educ & Clin Ctr, Salt Lake City, UT USA.
[Berlowitz, Dan R.] Bedford Vet Affairs Hosp, Bedford, MA USA.
[Berlowitz, Dan R.] Boston Univ, Sch Publ Hlth, Boston, MA USA.
[Campbell, Ruth C.] Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA.
[Chertow, Glenn M.] Stanford Univ, Sch Med, Dept Med, Palo Alto, CA 94304 USA.
[Fine, Larry J.] NHLBI, Div Cardiovasc Sci, Clin Applicat & Prevent Branch, Bldg 10, Bethesda, MD 20892 USA.
[Haley, William E.] Mayo Clin, Dept Hypertens & Nephrol, Jacksonville, FL 32224 USA.
[Hawfield, Amret T.] Wake Forest Sch Med, Nephrol Sect, Winston Salem, NC USA.
[Ix, Joachim H.] Univ Calif San Diego, Dept Med, Div Nephrol & Hypertens, San Diego, CA 92103 USA.
[Ix, Joachim H.] Univ Calif San Diego, Dept Family Med & Publ Hlth, Div Prevent Med, San Diego, CA 92103 USA.
[Ix, Joachim H.] Vet Affairs San Diego Healthcare Syst, Dept Med, Nephrol Sect, San Diego, CA USA.
[Kitzman, DalaneW.] Wake Forest Sch Med, Sect Cardiovasc Med, Winston Salem, NC USA.
[Kostis, John B.] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Cardiovasc Inst Rutgers, New Brunswick, NJ USA.
[Krousel-Wood, Marie A.] Tulane Univ, Sch Med, Dept Med, New Orleans, LA 70112 USA.
[Krousel-Wood, Marie A.] Tulane Univ, Dept Epidemiol, Sch Publ Hlth & Trop Med, New Orleans, LA 70118 USA.
[Krousel-Wood, Marie A.] Ochsner Clin Fdn, Ctr Appl Hlth Res, New Orleans, LA USA.
[Launer, Lenore J.] NIA, Intramural Res Program, Bethesda, MD 20892 USA.
[Oparil, Suzanne] Univ Alabama Birmingham, Dept Med, Div Cardiovasc Dis, Birmingham, AL 35294 USA.
[Rodriguez, Carlos J.] Wake Forest Sch Med, Dept Epidemiol & Prevent, Div Publ Hlth Sci, Winston Salem, NC USA.
[Roumie, Christianne L.] HSR&D Ctr, Vet Hlth Adm Tennessee Valley Healthcare Syst Ger, Nashville, TN USA.
[Roumie, Christianne L.] Vanderbilt Univ, Dept Med, Nashville, TN USA.
[Shorr, Ronald I.] Univ Florida, Dept Epidemiol, Gainesville, FL USA.
[Shorr, Ronald I.] Malcom Randall Vet Adm Med Ctr, Geriatr Res Educ & Clin Ctr, Gainesville, FL USA.
[Wadley, Virginia G.] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA.
[Whelton, Paul K.] Tulane Univ, Sch Publ Hlth & Trop Med, Dept Epidemiol, New Orleans, LA USA.
[Whittle, Jeffrey] Med Coll Wisconsin, Dept Med, Milwaukee, WI 53226 USA.
[Whittle, Jeffrey] Clement J Zablocki Vet Affairs Med Ctr, Primary Care Div, Milwaukee, WI USA.
[Wright, Jackson T., Jr.] Case Western Reserve Univ, Dept Med, Div Nephrol & Hypertens, Cleveland, OH 44106 USA.
Wake Forest Sch Med, Dept Biostat Sci, Div Publ Hlth Sci, Winston Salem, NC USA.
RP Williamson, JD (reprint author), Wake Forest Sch Med, Med Ctr Blvd, Dept Internal Med, Sect Gerontol & Geriatr Med,Sticht Ctr Aging, Winston Salem, NC 27157 USA.; Williamson, JD (reprint author), Wake Forest Sch Med, Med Ctr Blvd, Sect Gerontol & Geriatr Med, Winston Salem, NC 27157 USA.
EM jwilliam@wakehealth.edu
FU National Institutes of Health (National Heart, Lung, and Blood
Institute) [HHSN268200900040C, HHSN268200900046C, HHSN268200900047C,
HHSN268200900048C, HHSN268200900049C, A-HL-13-002-001]; National
Institutes of Health (National Institute of Diabetes and Digestive and
Kidney Diseases) [HHSN268200900040C, HHSN268200900046C,
HHSN268200900047C, HHSN268200900048C, HHSN268200900049C,
A-HL-13-002-001]; National Institutes of Health (National Institute on
Aging) [HHSN268200900040C, HHSN268200900046C, HHSN268200900047C,
HHSN268200900048C, HHSN268200900049C, A-HL-13-002-001]; National
Institutes of Health (National Institute of Neurological Disorders and
Stroke) [HHSN268200900040C, HHSN268200900046C, HHSN268200900047C,
HHSN268200900048C, HHSN268200900049C, A-HL-13-002-001]; Department of
Veterans Affairs; Wake Forest Claude Pepper Older Americans Independence
Center [P30-AG21332, R01-HL10741]; National Center for Advancing
Translational Sciences [UL1TR000439, UL1RR025755, UL1RR024134,
UL1TR000003, UL1RR025771, UL1TR000093, UL1RR025752, UL1TR000073,
UL1TR001064, UL1TR000050, UL1TR000005, 9U54TR000017-06, UL1TR000105-05,
UL1 TR000064, UL1TR000433]; National Institute of General Medical
Sciences, Centers of Biomedical Research Excellence [NIGMS P30GM103337]
FX The SPRINT study was funded by the National Institutes of Health
(including the National Heart, Lung, and Blood Institute, the National
Institute of Diabetes and Digestive and Kidney Diseases, the National
Institute on Aging, and the National Institute of Neurological Disorders
and Stroke) under contracts HHSN268200900040C, HHSN268200900046C,
HHSN268200900047C, HHSN268200900048C, and HHSN268200900049C and
interagency agreement A-HL-13-002-001. It was also supported in part
with resources and use of facilities through the Department of Veterans
Affairs. Azilsartan and chlorthalidone (combined with azilsartan) were
provided by Takeda Pharmaceuticals International Inc. Additional support
was provided by grants P30-AG21332 and R01-HL10741 from the Wake Forest
Claude Pepper Older Americans Independence Center; through the following
National Center for Advancing Translational Sciences clinical and
translational science awards: UL1TR000439 (awarded to Case Western
Reserve University); UL1RR025755 (Ohio State University); UL1RR024134
and UL1TR000003 (University of Pennsylvania); UL1RR025771 (Boston
University); UL1TR000093 (Stanford University); UL1RR025752,
UL1TR000073, and UL1TR001064 (Tufts University); UL1TR000050 (University
of Illinois); UL1TR000005 (University of Pittsburgh); 9U54TR000017-06
(University of Texas Southwestern Medical Center); UL1TR000105-05
(University of Utah); UL1 TR000445 (Vanderbilt University); UL1TR000075
(George Washington University); UL1 TR000002 (University of California,
Davis); UL1 TR000064 (University of Florida); and UL1TR000433
(University of Michigan); and by National Institute of General Medical
Sciences, Centers of Biomedical Research Excellence award NIGMS
P30GM103337 (awarded to Tulane University).
NR 34
TC 52
Z9 52
U1 4
U2 11
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 0098-7484
EI 1538-3598
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD JUN 28
PY 2016
VL 315
IS 24
BP 2673
EP 2682
DI 10.1001/jama.2016.7050
PG 10
WC Medicine, General & Internal
SC General & Internal Medicine
GA DP7WG
UT WOS:000378709300018
PM 27195814
ER
PT J
AU Vermeulen, E
Stronks, K
Visser, M
Brouwer, IA
Schene, AH
Mocking, RJT
Colpo, M
Bandinelli, S
Ferrucci, L
Nicolaou, M
AF Vermeulen, Esther
Stronks, Karien
Visser, Marjolein
Brouwer, Ingeborg A.
Schene, Aart H.
Mocking, Roel J. T.
Colpo, Marco
Bandinelli, Stefania
Ferrucci, Luigi
Nicolaou, Mary
TI The association between dietary patterns derived by reduced rank
regression and depressive symptoms over time: the Invecchiare in Chianti
(InCHIANTI) study
SO BRITISH JOURNAL OF NUTRITION
LA English
DT Article
DE Depressive symptoms; Diet; Dietary patterns; Reduced rank regression;
Invecchiare in Chianti study
ID SCALE CES-D; MEDITERRANEAN DIET; FURUKAWA NUTRITION; CRITERION VALIDITY;
JAPANESE EMPLOYEES; MAGNESIUM INTAKE; SUN COHORT; ADULTS; COMMUNITY;
WOMEN
AB This study aimed to identify dietary patterns using reduced rank regression (RRR) and to explore their associations with depressive symptoms over 9 years in the Invecchiare in Chianti study. At baseline, 1362 participants (55.4% women) aged 18-102 years (mean age 68 (SD 15.5) years) were included in the study. Baseline data collection started in 1998 and was repeated after 3, 6 and 9 years. Dietary intake information was obtained using a country-specific, validated FFQ with 188 food items. For baseline diet, dietary pattern scores in quartiles (Q) were derived using RRR with the nutrients EPA+DHA, folate, Mg and Zn as response variables. Continuous depression scores from the Centre for Epidemiologic Studies Depression (CES-D) scale were used for assessing depressive symptoms. The derived dietary pattern was rich in vegetables, olive oil, grains, fruit, fish and moderate in wine and red and processed meat, and was labelled as 'typical Tuscan dietary pattern'. After full adjustment, an inverse association was observed between this dietary pattern and depressive symptoms at baseline (Q1 v. Q4, B -2.77; 95% CI -4.55, -0.98). When examining the relationship between the above-mentioned dietary pattern at baseline and depressive symptoms over 9 years, a similar association was found after full adjustment for confounding factors (Q1 v. Q4, B -1.78; 95% CI -3.17, -0.38). A diet rich in vegetables, olive oil, grains, fruits, fish and moderate in wine and red and processed meat was consistently associated with lower CES-D scores over a 9-year period in the Tuscan population.
C1 [Vermeulen, Esther; Stronks, Karien; Nicolaou, Mary] Univ Amsterdam, Acad Med Ctr, Dept Publ Hlth, Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands.
[Visser, Marjolein; Brouwer, Ingeborg A.] Vrije Univ Amsterdam, EMGO Inst, Dept Hlth Sci, NL-1081 HV Amsterdam, Netherlands.
[Visser, Marjolein] Vrije Univ Amsterdam, Med Ctr, Internal Med, Dept Nutr & Dietet, NL-1081 HV Amsterdam, Netherlands.
[Schene, Aart H.; Mocking, Roel J. T.] Univ Amsterdam, Acad Med Ctr, Dept Psychiat, Program Mood Disorders, Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands.
[Schene, Aart H.] Radboud Univ Nijmegen, Med Ctr, Dept Psychiat, NL-6525 GA Nijmegen, Netherlands.
[Schene, Aart H.] Radboud Univ Nijmegen, Donders Inst Brain Cognit & Behav, NL-6525 HP Nijmegen, Netherlands.
[Bandinelli, Stefania] Azienda Sanit Firenze, InCHIANTI Study Grp, I-50125 Florence, Italy.
[Ferrucci, Luigi] NIA, Longitudinal Studies Sect, Baltimore, MD 21224 USA.
RP Vermeulen, E (reprint author), Univ Amsterdam, Acad Med Ctr, Dept Publ Hlth, Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands.
EM e.vermeulen@amc.uva.nl
FU EU [613598]; Italian Ministry of Health [ICS110.1/RF97.71]; US National
Institute on Aging, Bethesda, MD [236 MD 916413, 236 MD 821336]; US
National Institute on Aging [N.1-AG-1-1, N.1-AG-1-2111]; US National
Institute on Aging - National Institute on Aging, National Institutes of
Health [N01-AG-5-0002]
FX Funding for this research was provided by EU FP7 MooD-FOOD Project
'Multi-country cOllaborative project on the rOle of Diet, FOod-related
behaviour, and Obesity in the prevention of Depression', grant agreement
no. 613598. The InCHIANTI study baseline (1998-2000) was funded by the
Italian Ministry of Health (ICS110.1/RF97.71) and in part by the US
National Institute on Aging, Bethesda, MD (contracts: 236 MD 916413 and
236 MD 821336). The InCHIANTI follow-up 1 (2001-2003) was funded by the
US National Institute on Aging (contracts: N.1-AG-1-1 and
N.1-AG-1-2111); the InCHIANTI follow-ups two and three (2004-2010) were
financed by the US National Institute on Aging (contract:
N01-AG-5-0002), supported in part by the Intramural Research Program of
the National Institute on Aging, National Institutes of Health.
NR 46
TC 0
Z9 0
U1 5
U2 9
PU CAMBRIDGE UNIV PRESS
PI CAMBRIDGE
PA EDINBURGH BLDG, SHAFTESBURY RD, CB2 8RU CAMBRIDGE, ENGLAND
SN 0007-1145
EI 1475-2662
J9 BRIT J NUTR
JI Br. J. Nutr.
PD JUN 28
PY 2016
VL 115
IS 12
BP 2145
EP 2153
DI 10.1017/S0007114516001318
PG 9
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA DO7PB
UT WOS:000377973400008
PM 27080555
ER
PT J
AU Nagaya, T
Nakamura, Y
Sato, K
Harada, T
Choyke, PL
Kobayashi, H
AF Nagaya, Tadanobu
Nakamura, Yuko
Sato, Kazuhide
Harada, Toshiko
Choyke, Peter L.
Kobayashi, Hisataka
TI Improved micro-distribution of antibody-photon absorber conjugates after
initial near infrared photoimmunotherapy (NIR-PIT)
SO JOURNAL OF CONTROLLED RELEASE
LA English
DT Article
DE Photoimmunotherapy; Enhanced permeability and retention effect; Drug
delivery; Micro distribution; Near infrared light
ID PHOTODYNAMIC THERAPY; CANCER-CELLS; IN-VIVO; ENHANCED PERMEABILITY;
TUMOR; MOUSE; CHEMOSENSITIVITY; METASTASIS; DELIVERY; CYCLE
AB Near infrared photoimmunotherapy (NIR-PIT), a targeted cancer therapy which uses an antibody-photo absorber conjugate (APC) and near infrared light exposure, dramatically improves nano-drug delivery into treated tumor beds due to enhanced vascular permeability. We investigated the micro-distribution of APCs in a variety of NIR-PIT treated tumors. Either cetuximab (cet) or trastuzumab (tra) conjugated with IR700 (cet-tra-IR700) was administered, as appropriate, to each mouse model of tumor. Tumor-bearing mice implanted with A431-GFP, MDAMB468-GFP, 3T3Her2-GFP or N87-GFP were separated into 5 groups: group 1 = no treatment; group 2 = cet-tra-IR700 i.v., no light exposure; group 3 = cet-tra-IR700 i.v., NIR light exposure; group 4 = cet-tra-IR700 i.v. and additional cet-tra-IR700 i.v. at 24 h but no light exposure; group 5 = cet-tra-IR700 i.v., NIR light exposure and additional cet-tra-IR700 i.v. immediately after NIR but no additional NIR light exposure. In vivo, ex vivo and microscopic fluorescence imaging was performed. Fluorescence from the surface of the tumor (s-tumor) was compared to fluorescence from deeper areas of the tumor (d-tumor). In general, therewas no significant difference in the fluorescence intensity of GFP in the tumors among all groups, however the highest IR700 fluorescence intensity was consistently shown in group 5 tumors due to added APC after NIR-PIT. Fluorescence microscopy in all tumor types demonstrated that GFP relative fluorescence intensity (RFI) in s-tumor was significantly lower in group 3 and 5 (NIR-PIT groups) than in group 1, 2, and 4 (no NIR-PIT) yet there was no significant difference in d-tumor RFI among all groups. IR700 fluorescent RFI in the d-tumor was highest in group 5 (NIR-PIT + additional APC) compared to the other groups. Cell killing after NIR-PIT was primarily on the surface, however, APCs administered immediately after NIR-PIT penetrated deeper into tissue resulting in improved cell killing after a 2nd NIR-PIT session. This phenomenon is explained by increased vascular permeability immediately after NIR-PIT. Published by Elsevier B.V.
C1 [Nagaya, Tadanobu; Nakamura, Yuko; Sato, Kazuhide; Harada, Toshiko; Choyke, Peter L.; Kobayashi, Hisataka] NCI, Mol Imaging Program, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Kobayashi, H (reprint author), NCI, Mol Imaging Program, Ctr Canc Res, Bethesda, MD 20892 USA.
EM kobayash@mail.nih.gov
FU Intramural Research Program of the National Institutes of Health,
National Cancer Institute, Center for Cancer Research [ZIA BC 011513];
JSPS
FX This research was supported by the Intramural Research Program of the
National Institutes of Health, National Cancer Institute, Center for
Cancer Research (ZIA BC 011513). Kazuhide Sato is supported with JSPS
Research Fellowship for Japanese Biomedical and Behavioral Researchers
at NIH.
NR 25
TC 3
Z9 3
U1 12
U2 23
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0168-3659
EI 1873-4995
J9 J CONTROL RELEASE
JI J. Control. Release
PD JUN 28
PY 2016
VL 232
BP 1
EP 8
DI 10.1016/j.jconrel.2016.04.003
PG 8
WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy
SC Chemistry; Pharmacology & Pharmacy
GA DN9LL
UT WOS:000377401000001
PM 27059723
ER
PT J
AU Liu, JJ
Liu, JY
Chen, J
Wu, YX
Yan, P
Ji, CD
Wang, YX
Xiang, DF
Zhang, X
Zhang, P
Cui, YH
Wang, JM
Bian, XW
Qian, F
AF Liu, Jia-jia
Liu, Jun-yan
Chen, Jun
Wu, Yi-xi
Yan, Peng
Ji, Cheng-dong
Wang, Yan-xia
Xiang, Dong-fang
Zhang, Xia
Zhang, Peng
Cui, You-hong
Wang, Ji Ming
Bian, Xiu-wu
Qian, Feng
TI Scinderin promotes the invasion and metastasis of gastric cancer cells
and predicts the outcome of patients
SO CANCER LETTERS
LA English
DT Article
DE Scinderin; Gastric cancer; Invasion; Metastasis; Filopodia; Cdc42
ID EPITHELIAL-MESENCHYMAL TRANSITION; SEVERING PROTEIN ADSEVERIN; HUMAN
BLADDER-CANCER; MOLECULAR ARCHITECTURE; INHIBITS PROLIFERATION; ACTIN
CYTOSKELETON; DIFFERENTIATION; FILOPODIA; MOTILITY; MIGRATION
AB Invasion and metastasis are major malignant characteristics of human gastric cancer (GC), but the underlying molecular mechanisms are poorly understood. Recent studies have shown that scinderin (SCIN), an actin severing and capping protein that regulates the actin cytoskeleton, is involved in the proliferation and migration of certain cancer cells. Accordingly, this study aimed to investigate the potential role of SCIN in the invasion and metastasis of human GC cells and to evaluate its prognostic value for GC patients. We found that high levels of SCIN expression in GC tumors were correlated with poor overall survival of patients. Silencing of SCIN effectively suppressed the migratory and invasive capabilities of human GC cells in vitro and tumorigenicity and metastasis in vivo. Furthermore, knockdown of SCIN markedly inhibited the formation of filopodia, decreasing GC cell migration and the expression of Cdc42, an important regulator of filopodia by GC cells. These findings suggest that SCIN may be a novel prognostic marker and a potential therapeutic target in human GC. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
C1 [Liu, Jia-jia; Liu, Jun-yan; Chen, Jun; Wu, Yi-xi; Yan, Peng; Qian, Feng] Third Mil Med Univ, Southwest Hosp, Dept Gen Surg, Chongqing 400038, Peoples R China.
[Liu, Jia-jia; Liu, Jun-yan; Chen, Jun; Wu, Yi-xi; Yan, Peng; Qian, Feng] Third Mil Med Univ, Southwest Hosp, Ctr Minimal Invas Gastrointestinal Surg, Chongqing 400038, Peoples R China.
[Ji, Cheng-dong; Wang, Yan-xia; Xiang, Dong-fang; Zhang, Xia; Zhang, Peng; Cui, You-hong; Wang, Ji Ming; Bian, Xiu-wu] Third Mil Med Univ, Southwest Hosp, Inst Pathol, Key Lab Tumor Immunopathol,Minist Educ China, Chongqing 400038, Peoples R China.
[Ji, Cheng-dong; Wang, Yan-xia; Xiang, Dong-fang; Zhang, Xia; Zhang, Peng; Cui, You-hong; Wang, Ji Ming; Bian, Xiu-wu] Third Mil Med Univ, Southwest Hosp, Southwest Canc Ctr, Key Lab Tumor Immunopathol,Minist Educ China, Chongqing 400038, Peoples R China.
[Wang, Ji Ming] NCI, Canc & Inflammat Program, Ctr Canc Res, Frederick, MD 21702 USA.
RP Qian, F (reprint author), Third Mil Med Univ, Southwest Hosp, Dept Gen Surg, Chongqing 400038, Peoples R China.; Qian, F (reprint author), Third Mil Med Univ, Southwest Hosp, Ctr Minimal Invas Gastrointestinal Surg, Chongqing 400038, Peoples R China.; Bian, XW (reprint author), Third Mil Med Univ, Southwest Hosp, Inst Pathol, Key Lab Tumor Immunopathol,Minist Educ China, Chongqing 400038, Peoples R China.; Bian, XW (reprint author), Third Mil Med Univ, Southwest Hosp, Southwest Canc Ctr, Key Lab Tumor Immunopathol,Minist Educ China, Chongqing 400038, Peoples R China.
EM bianxiuwu@263.net; qianfengpuwaia@163.com
RI Bian, Xiu-wu/D-4736-2017; Zhang, Xia/B-8152-2008
OI Bian, Xiu-wu/0000-0003-4383-0197; Zhang, Xia/0000-0002-9040-1486
FU National Science Foundation of China [81272365, 81372555]
FX This project was supported by grants from the National Science
Foundation of China (Nos. 81272365 and 81372555). We thank Prof. Pei-wu
Yu (Institute of Pathology and Southwest Cancer Center, Southwest
Hospital, Third Military Medical University, Chongqing, China) for
supporting this work. We thank Mrs. Ze-xuan Yan (Institute of Pathology
and Southwest Cancer Center, Southwest Hospital, Third Military Medical
University, Chongqing, China) for technical assistance in cell culture.
NR 42
TC 0
Z9 0
U1 3
U2 10
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0304-3835
EI 1872-7980
J9 CANCER LETT
JI Cancer Lett.
PD JUN 28
PY 2016
VL 376
IS 1
BP 110
EP 117
DI 10.1016/j.canlet.2016.03.035
PG 8
WC Oncology
SC Oncology
GA DL8IP
UT WOS:000375886000012
PM 27033455
ER
PT J
AU Surewaard, BGJ
Deniset, JF
Zemp, FJ
Amrein, M
Otto, M
Conly, J
Omri, A
Yates, RM
Kubes, P
AF Surewaard, Bas G. J.
Deniset, Justin F.
Zemp, Franz J.
Amrein, Matthias
Otto, Michael
Conly, John
Omri, Abdelwahab
Yates, Robin M.
Kubes, Paul
TI Identification and treatment of the Staphylococcus aureus reservoir in
vivo
SO JOURNAL OF EXPERIMENTAL MEDICINE
LA English
DT Article
ID S. AUREUS; INFECTIONS; BACTEREMIA; VANCOMYCIN; MANAGEMENT; EPIDEMIOLOGY;
PHAGOCYTOSIS; MACROPHAGES; NEUTROPHILS; ACTIVATION
AB Methicillin-resistant Staphylococcus aureus (MRSA) bacteremia is reaching epidemic proportions causing morbidity, mortality, and chronic disease due to relapses, suggesting an intracellular reservoir. Using spinning-disk confocal intravital microscopy to track MRSA-GFP in vivo, we identified that within minutes after intravenous infection MRSA is primarily sequestered and killed by intravascular Kupffer cells (KCs) in the liver. However, a minority of the Staphylococci overcome the KC's antimicrobial defenses. These bacteria survive and proliferate for many days within this intracellular niche, where they remain undetected by recruited neutrophils. Over time, the KCs lyse, releasing bacteria into the circulation, enabling dissemination to other organs such as the kidneys. Vancomycin, the antibiotic of choice to treat MRSA bacteremia, could not penetrate the KCs to eradicate intracellular MRSA. However, based on the intravascular location of these specific macrophages, we designed a liposomal formulation of vancomycin that is efficiently taken up by KCs and diminished the intracellular MRSA. Targeting the source of the reservoir dramatically protected the liver but also dissemination to other organs, and prevented mortality. This vancomycin formulation strategy could help treat patients with Staphylococcal bacteremia without a need for novel antibiotics by targeting the previously inaccessible intracellular reservoir in KCs.
C1 [Surewaard, Bas G. J.; Deniset, Justin F.; Zemp, Franz J.; Conly, John; Yates, Robin M.; Kubes, Paul] Univ Calgary, Snyder Inst Chron Dis, Calgary, AB T2N 1N4, Canada.
[Amrein, Matthias] Univ Calgary, Dept Cell Biol & Anat, Calgary, AB T2N 1N4, Canada.
[Conly, John] Univ Calgary, Dept Med, Cumming Sch Med, Calgary, AB T2N 1N4, Canada.
[Conly, John] Univ Calgary, Dept Pathol & Lab Med, Calgary, AB T2N 1N4, Canada.
[Conly, John] Univ Calgary, Dept Microbiol Infect Dis & Immunol, Calgary, AB T2N 1N4, Canada.
[Yates, Robin M.] Univ Calgary, Dept Comparat Biol & Expt Med, Fac Vet Med, Calgary, AB T2N 1N4, Canada.
[Kubes, Paul] Univ Calgary, Dept Physiol & Pharmacol, Calgary, AB T2N 1N4, Canada.
[Surewaard, Bas G. J.] Univ Med Ctr, Dept Med Microbiol, NL-3584 CX Utrecht, Netherlands.
[Otto, Michael] NIAID, Pathogen Mol Genet Sect, Bacteriol Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Omri, Abdelwahab] Laurentian Univ, Dept Chem & Biochem, Sudbury, ON P3E 2C6, Canada.
RP Kubes, P (reprint author), Univ Calgary, Snyder Inst Chron Dis, Calgary, AB T2N 1N4, Canada.; Kubes, P (reprint author), Univ Calgary, Dept Physiol & Pharmacol, Calgary, AB T2N 1N4, Canada.
EM pkubes@ucalgary.ca
RI Yates, Robin/K-5032-2015
OI Yates, Robin/0000-0003-3122-1845
FU Alberta Innovates Health Solutions (AIHS); Canadian Institutes of Health
Research; Canada Research Chairs Program; Marie Currie actions
FP7-PEOPLE-IOF [627575]; AIHS
FX P. Kubes is supported by Alberta Innovates Health Solutions (AIHS), the
Canadian Institutes of Health Research, and the Canada Research Chairs
Program. B.G.J. Surewaard is partially funded by Marie Currie actions
FP7-PEOPLE-2013-IOF (grant no. 627575) and AIHS. J.F. Deniset and F.J.
Zemp are financially supported by AIHS.
NR 33
TC 2
Z9 2
U1 7
U2 10
PU ROCKEFELLER UNIV PRESS
PI NEW YORK
PA 950 THIRD AVE, 2ND FLR, NEW YORK, NY 10022 USA
SN 0022-1007
EI 1540-9538
J9 J EXP MED
JI J. Exp. Med.
PD JUN 27
PY 2016
VL 213
IS 7
BP 1141
EP 1151
DI 10.1084/jem.20160334
PG 11
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA DS5VA
UT WOS:000380849800005
PM 27325887
ER
PT J
AU Avery, CL
Holliday, KM
Chakladar, S
Engeda, JC
Hardy, ST
Reis, JP
Schreiner, PJ
Shay, CM
Daviglus, ML
Heiss, G
Lin, DY
Zeng, DL
AF Avery, Christy L.
Holliday, Katelyn M.
Chakladar, Sujatro
Engeda, Joseph C.
Hardy, Shakia T.
Reis, Jared P.
Schreiner, Pamela J.
Shay, Christina M.
Daviglus, Martha L.
Heiss, Gerardo
Lin, Dan Yu
Zeng, Donglin
TI Disparities in Early Transitions to Obesity in Contemporary Multi-Ethnic
US Populations
SO PLOS ONE
LA English
DT Article
ID BODY-MASS INDEX; UNITED-STATES; CARDIOVASCULAR-DISEASE;
AMERICAN-INDIANS; YOUNG ADULTHOOD; WEIGHT-GAIN; MIDDLE-AGE; OVERWEIGHT;
RISK; METAANALYSIS
AB Background
Few studies have examined weight transitions in contemporary multi-ethnic populations spanning early childhood through adulthood despite the ability of such research to inform obesity prevention, control, and disparities reduction.
Methods and Results
We characterized the ages at which African American, Caucasian, and Mexican American populations transitioned to overweight and obesity using contemporary and nationally representative cross-sectional National Health and Nutrition Examination Survey data (n = 21,220; aged 2-80 years). Age-, sex-, and race/ethnic-specific one-year net transition probabilities between body mass index-classified normal weight, overweight, and obesity were estimated using calibrated and validated Markov-type models that accommodated complex sampling. At age two, the obesity prevalence ranged from 7.3% in Caucasian males to 16.1% in Mexican American males. For all populations, estimated one-year overweight to obesity net transition probabilities peaked at age two and were highest for Mexican American males and African American females, for whom a net 12.3%(95% CI: 7.6%-17.0%) and 11.9% (95% CI: 8.5%-15.3%) of the overweight populations transitioned to obesity by age three, respectively. However, extrapolation to the 2010 U.S. population demonstrated that Mexican American males were the only population for whom net increases in obesity peaked during early childhood; age-specific net increases in obesity were approximately constant through the second decade of life for African Americans and Mexican American females and peaked at age 20 for Caucasians.
Conclusions
African American and Mexican American populations shoulder elevated rates of many obesity-associated chronic diseases and disparities in early transitions to obesity could further increase these inequalities if left unaddressed.
C1 [Avery, Christy L.; Holliday, Katelyn M.; Engeda, Joseph C.; Hardy, Shakia T.; Heiss, Gerardo] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA.
[Chakladar, Sujatro; Lin, Dan Yu; Zeng, Donglin] Univ N Carolina, Dept Biostat, Chapel Hill, NC USA.
[Reis, Jared P.] NHLBI, Epidemiol Branch, Populat & Prevent Sci Program, Div Cardiovasc Sci, Bldg 10, Bethesda, MD 20892 USA.
[Schreiner, Pamela J.] Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN USA.
[Shay, Christina M.] Univ N Carolina, Dept Nutr, Chapel Hill, NC USA.
[Daviglus, Martha L.] Univ Illinois, Dept Med, Inst Minor Hlth Res, Chicago, IL USA.
RP Avery, CL (reprint author), Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA.
EM Christy_avery@unc.edu
FU National Heart, Lung, and Blood Institute (NHLBI) [AG0005]; University
of Alabama at Birmingham [HHSN268201300025C, HHSN268201300026C];
Northwestern University [HHSN268201300027C]; University of Minnesota
[HHSN268201300028C]; Kaiser Foundation Research Institute
[HHSN268201300029C]; Johns Hopkins University School of Medicine
[HHSN268200900041C]; Intramural Research Program of the National
Institute on Aging (NIA); NIA [AG0005]
FX This publication was made possible in part by R21HL121580, R00HL098458,
and T32HL007055. The Coronary Artery Risk Development in Young Adults
Study (CARDIA) is conducted and supported by the National Heart, Lung,
and Blood Institute (NHLBI) in collaboration with the University of
Alabama at Birmingham HHSN268201300025C & HHSN268201300026C),
Northwestern University (HHSN268201300027C), University of Minnesota
(HHSN268201300028C), Kaiser Foundation Research Institute
(HHSN268201300029C), and Johns Hopkins University School of Medicine
(HHSN268200900041C). CARDIA is also partially supported by the
Intramural Research Program of the National Institute on Aging (NIA) and
an intra-agency agreement between NIA and NHLBI (AG0005). This
manuscript has been reviewed by CARDIA for scientific content.
NR 38
TC 0
Z9 0
U1 1
U2 3
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUN 27
PY 2016
VL 11
IS 6
AR e0158025
DI 10.1371/journal.pone.0158025
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DP9FD
UT WOS:000378801200028
PM 27348868
ER
PT J
AU Pierce, JV
Bernstein, HD
AF Pierce, Jessica V.
Bernstein, Harris D.
TI Genomic Diversity of Enterotoxigenic Strains of Bacteroides fragilis
SO PLOS ONE
LA English
DT Article
ID SECRETION SYSTEM EFFECTORS; HUMAN GUT; ANTIMICROBIAL RESISTANCE;
PATHOGENICITY ISLAND; COLON CARCINOGENESIS; BACTERIAL BIOFILMS; TOXIN
GENE; MICROBIOTA; SYMBIONT; METALLOPROTEASE
AB Enterotoxigenic (ETBF) strains of Bacteroides fragilis are the subset of strains that secrete a toxin called fragilysin (Bft). Although ETBF strains are known to cause diarrheal disease and have recently been associated with colorectal cancer, they have not been well characterized. By sequencing the complete genome of four ETBF strains, we found that these strains exhibit considerable variation at the genomic level. Only a small number of genes that are located primarily in the Bft pathogenicity island (BFT PAI) and the flanking CTn86 conjugative transposon are conserved in all four strains and a fifth strain whose genome was previously sequenced. Interestingly, phylogenetic analysis strongly suggests that the BFT PAI was acquired by non-toxigenic (NTBF) strains multiple times during the course of evolution. At the phenotypic level, we found that the ETBF strains were less fit than the NTBF strain NCTC 9343 and were susceptible to a growth-inhibitory protein that it produces. The ETBF strains also showed a greater tendency to form biofilms, which may promote tumor formation, than NTBF strains. Although the genomic diversity of ETBF strains raises the possibility that they vary in their pathogenicity, our experimental results also suggest that they share common properties that are conferred by different combinations of non-universal genetic elements.
C1 [Pierce, Jessica V.; Bernstein, Harris D.] NIDDK, Genet & Biochem Branch, NIH, Bethesda, MD 20892 USA.
RP Bernstein, HD (reprint author), NIDDK, Genet & Biochem Branch, NIH, Bethesda, MD 20892 USA.
EM harris_bernstein@nih.gov
FU Intramural Research Program of the National Institute of Diabetes and
Digestive and Kidney Diseases
FX This work was supported by the Intramural Research Program of the
National Institute of Diabetes and Digestive and Kidney Diseases. The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.; We would like to
thank Cynthia Sears and Andy Goodman for the gift of B. fragilis strains
and Harold Smith (NIDDK Genomics Core) for sequencing the genome of ETBF
strain 2-078382-3 and providing bioinformatics support. We would also
like to thank Marlena Wilson for the anti-TssD antiserum and for helpful
discussions. This work was supported by the Intramural Research Program
of the National Institute of Diabetes and Digestive and Kidney Diseases.
NR 52
TC 0
Z9 0
U1 3
U2 3
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUN 27
PY 2016
VL 11
IS 6
AR e0158171
DI 10.1371/journal.pone.0158171
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DP9FD
UT WOS:000378801200043
PM 27348220
ER
PT J
AU Wang, RH
Zhao, TR
Cui, KR
Hu, GQ
Chen, Q
Chen, WP
Wang, XW
Soto-Gutierrez, A
Zhao, KJ
Deng, CX
AF Wang, Rui-Hong
Zhao, Tingrui
Cui, Kairong
Hu, Gangqing
Chen, Qiang
Chen, Weiping
Wang, Xin-Wei
Soto-Gutierrez, Alejandro
Zhao, Keji
Deng, Chu-Xia
TI Negative reciprocal regulation between Sirt1 and Per2 modulates the
circadian clock and aging
SO SCIENTIFIC REPORTS
LA English
DT Article
ID LIFE-SPAN; TUMOR-SUPPRESSOR; CALORIE RESTRICTION; DEACETYLASE SIRT1;
MUTANT MICE; DNA-DAMAGE; P53; METABOLISM; RHYTHMS; PROTEIN
AB Sirtuin 1 (SIRT1) is involved in both aging and circadian-clock regulation, yet the link between the two processes in relation to SIRT1 function is not clear. Using Sirt1-deficient mice, we found that Sirt1 and Period 2 (Per2) constitute a reciprocal negative regulation loop that plays important roles in modulating hepatic circadian rhythmicity and aging. Sirt1-deficient mice exhibited profound premature aging and enhanced acetylation of histone H4 on lysine16 (H4K16) in the promoter of Per2, the latter of which leads to its overexpression; in turn, Per2 suppresses Sirt1 transcription through binding to the Sirt1 promoter at the Clock/Bmal1 site. This negative reciprocal relationship between SIRT1 and PER2 was also observed in human hepatocytes. We further demonstrated that the absence of Sirt1 or the ectopic overexpression of Per2 in the liver resulted in a dysregulated pace of the circadian rhythm. The similar circadian rhythm was also observed in aged wild type mice. The interplay between Sirt1 and Per2 modulates aging gene expression and circadian-clock maintenance.
C1 [Wang, Rui-Hong; Chen, Qiang; Deng, Chu-Xia] Univ Macau, Fac Hlth Sci, Macau, Peoples R China.
[Wang, Rui-Hong; Zhao, Tingrui; Deng, Chu-Xia] NIDDK, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA.
[Cui, Kairong; Hu, Gangqing; Zhao, Keji] NHLBI, Syst Biol Ctr, Bethesda, MD 20892 USA.
[Chen, Weiping] NIDDK, Genom Core Lab, Bethesda, MD 20892 USA.
[Wang, Xin-Wei] NCI, Lab Human Carcinogenesis, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Soto-Gutierrez, Alejandro] Univ Pittsburgh, Dept Pathol, Pittsburgh, PA 15213 USA.
RP Deng, CX (reprint author), Univ Macau, Fac Hlth Sci, Macau, Peoples R China.; Deng, CX (reprint author), NIDDK, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA.
EM cxdeng@umac.mo
RI deng, chuxia/N-6713-2016; Wang, Xin/B-6162-2009
FU Intramural Research Program of the National Institute of DIDDK, National
Institutes of Health, Bethesda, MD, USA; Intramural Research Program of
the National Institute of NHLBI, National Institutes of Health,
Bethesda, MD, USA; Intramural Research Program of the National Institute
of NCI, National Institutes of Health, Bethesda, MD, USA; Faculty of
Health Sciences, University of Macau, Macau SAR, China
FX We gratefully acknowledge members of the Deng laboratory for helpful
discussions. The ChIP-Seq libraries were sequenced by the DNA Sequencing
and Computation Core facility of the National Heart, Lung, and Blood
Institute (NHLBI). Freshly isolated human hepatocytes were obtained from
the Liver Tissue Cell Distribution System at the University of
Pittsburgh (Pittsburgh, PA). This work was supported, in part, by the
Intramural Research Programs of the National Institute of DIDDK, NHLBI,
and NCI, National Institutes of Health, Bethesda, MD, USA, as well as
the Faculty of Health Sciences, University of Macau, Macau SAR, China.
NR 57
TC 1
Z9 2
U1 3
U2 7
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2045-2322
J9 SCI REP-UK
JI Sci Rep
PD JUN 27
PY 2016
VL 6
AR 28633
DI 10.1038/srep28633
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DP5DD
UT WOS:000378515300001
PM 27346580
ER
PT J
AU White, CL
Kessler, PM
Dickerman, BK
Ozato, K
Sen, GC
AF White, Christine L.
Kessler, Patricia M.
Dickerman, Benjamin K.
Ozato, Keiko
Sen, Ganes C.
TI Interferon Regulatory Factor 8 (IRF8) Impairs Induction of Interferon
Induced with Tetratricopeptide Repeat Motif (IFIT) Gene Family Members
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
DE gene regulation; interferon; interferon regulatory factor (IRF);
promoter; transcription regulation
ID SEQUENCE-BINDING-PROTEIN; INDUCIBLE HUMAN GENES; RIG-I; TRANSCRIPTION
FACTOR; ALPHA; MOUSE; ACTIVATION; EXPRESSION; COMPLEX; RNA
AB The chromosomally clustered interferon-induced with tetratricopeptide repeat motif (IFIT) gene family members share structural features at the gene and protein levels. Despite these similarities, different IFIT genes have distinct inducer- and cell type-specific induction patterns. Here, we investigated the mechanism for the observed differential induction of the mouse Ifit1, Ifit2, and Ifit3 genes in B cells and demonstrated that the repressive effect of the transcription factor interferon regulatory factor 8 (IRF8), which is highly expressed in B cells, played an essential role in this regulation. Although IRF8 could impair induction of all three IFIT genes following stimulation of retinoic acid-inducible gene I (RIG-I), it could selectively impair the induction of the Ifit1 gene following IFN stimulation. The above properties could be imparted to IRF8-non-expressing cells by ectopic expression of the protein. Induction of reporter genes, driven by truncated Ifit1 promoters, identified the regions that mediate the repression, and a chromatin immunoprecipitation assay revealed that more IRF8 bound to the IFN-stimulated response element of the Ifit1 gene than to those of the Ifit2 and the Ifit3 genes. Mutational analyses of IRF8 showed that its ability to bind DNA, interact with other proteins, and undergo sumoylation were all necessary to selectively repress Ifit1 gene induction in response to IFN. Our study revealed a new role for IRFs in differentially regulating the induction patterns of closely related IFN-stimulated genes that are located adjacent to one another in the mouse genome.
C1 [White, Christine L.; Kessler, Patricia M.; Dickerman, Benjamin K.; Sen, Ganes C.] Cleveland Clin, Lerner Res Inst, Dept Mol Genet, Cleveland, OH 44195 USA.
[Dickerman, Benjamin K.; Sen, Ganes C.] Case Western Reserve Univ, Grad Program Mol Virol, Cleveland, OH 44106 USA.
[Ozato, Keiko] NICHD, Program Genom Differentiat, NIH, Bethesda, MD 20892 USA.
[Dickerman, Benjamin K.] Burnet Inst Med Res, Melbourne, Vic 3004, Australia.
RP White, CL (reprint author), Hudson Inst Med Res, Ctr Canc Res, 27-31 Wright St, Clayton, Vic 3168, Australia.; Sen, GC (reprint author), Cleveland Clin, Dept Immunol NE20, 9500 Euclid Ave, Cleveland, OH 44195 USA.
EM christine.white@hudson.org.au; seng@ccf.org
OI White, Christine/0000-0002-5920-0029
FU National Institutes of Health [CA068782, CA062220, AI073303]
FX This work was supported by National Institutes of Health Grants
CA068782, CA062220, and AI073303 (to G. C. S.). The authors declare that
they have no conflicts of interest with the contents of this article.
The content is solely the responsibility of the authors and does not
necessarily represent the official views of the National Institutes of
Health.
NR 40
TC 0
Z9 0
U1 1
U2 2
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
EI 1083-351X
J9 J BIOL CHEM
JI J. Biol. Chem.
PD JUN 24
PY 2016
VL 291
IS 26
BP 13535
EP 13545
DI 10.1074/jbc.M115.705467
PG 11
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA DR2YZ
UT WOS:000379771100012
PM 27137933
ER
PT J
AU Graham, BS
AF Graham, Barney S.
TI Vaccines against respiratory syncytial virus: The time has finally come
SO VACCINE
LA English
DT Article
DE RSV; Immunization; Vaccination; Structure-based vaccine design; Fusion;
Neutralization; Vaccine-enhanced illness; Bronchiolitis; Pneumonia;
Infants; Elderly; Th2; Eosinophilia; Subunit vaccine; Vaccine vector;
Wheezing; Asthma; Protein conformation; Epitope
ID FUSION GLYCOPROTEIN; NEUTRALIZING ANTIBODY; RSV INFECTION; COTTON RATS;
STRUCTURAL-ANALYSIS; ANTIGENIC STRUCTURE; DISEASE SEVERITY; ATYPICAL
MEASLES; PRETERM INFANTS; FIELD TRIAL
AB Respiratory syncytial virus causes a significant public health burden, particularly in very young infants and the frail elderly. The legacy of enhanced RSV disease (ERD) from a whole formalin-inactivated RSV vaccine, and the complex biology of the virus and the neonate have delayed the development of effective vaccines. However, new insights into factors associated with ERD and breakthroughs in understanding the antigenic structure of the fusion (F) glycoprotein have increased optimism that vaccine development is possible. This has led to investment of time and resources by industry, regulatory authorities, governments, and nonprofit organizations to develop the infrastructure needed to make the advanced clinical development of RSV vaccine candidates a reality. Published by Elsevier Ltd.
C1 [Graham, Barney S.] NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
RP Graham, BS (reprint author), NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM bgraham@nih.gov
FU Vaccine Research Center, National Institute of Allergy and Infectious
Diseases, NIH
FX This work was supported by intramural funding from the Vaccine Research
Center, National Institute of Allergy and Infectious Diseases, NIH. The
author is a named inventor on patents for RSV vaccines involving subunit
F proteins and gene-based vector delivery of F. I thank Jason Gall and
Kaitlyn Morabito for thoughtful editorial comments on the manuscript.
NR 93
TC 9
Z9 9
U1 7
U2 10
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0264-410X
EI 1873-2518
J9 VACCINE
JI Vaccine
PD JUN 24
PY 2016
VL 34
IS 30
BP 3535
EP 3541
DI 10.1016/j.vaccine.2016.04.083
PG 7
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA DQ1IT
UT WOS:000378955400015
PM 27182820
ER
PT J
AU Pine, PS
Munro, SA
Parsons, JR
McDaniel, J
Lucas, AB
Lozach, J
Myers, TG
Su, Q
Jacobs-Helber, SM
Salit, M
AF Pine, P. Scott
Munro, Sarah A.
Parsons, Jerod R.
McDaniel, Jennifer
Lucas, Anne Bergstrom
Lozach, Jean
Myers, Timothy G.
Su, Qin
Jacobs-Helber, Sarah M.
Salit, Marc
TI Evaluation of the External RNA Controls Consortium (ERCC) reference
material using a modified Latin square design
SO BMC BIOTECHNOLOGY
LA English
DT Article
DE ERCC; Gene expression; Microarray; RNA controls; RNA sequencing;
RNA-Seq; Spike-in controls
ID GENE-EXPRESSION; SEQ EXPERIMENTS; DIFFERENTIAL GENE; DNA MICROARRAYS;
TRANSCRIPTOME; AMPLIFICATION; PERFORMANCE; MODELS; NOISE; CELLS
AB Background: Highly multiplexed assays for quantitation of RNA transcripts are being used in many areas of biology and medicine. Using data generated by these transcriptomic assays requires measurement assurance with appropriate controls. Methods to prototype and evaluate multiple RNA controls were developed as part of the External RNA Controls Consortium (ERCC) assessment process. These approaches included a modified Latin square design to provide a broad dynamic range of relative abundance with known differences between four complex pools of ERCC RNA transcripts spiked into a human liver total RNA background.
Results: ERCC pools were analyzed on four different microarray platforms: Agilent 1- and 2-color, Illumina bead, and NIAID lab-made spotted microarrays; and two different second-generation sequencing platforms: the Life Technologies 5500xl and the Illumina HiSeq 2500. Individual ERCC controls were assessed for reproducible performance in signal response to concentration among the platforms. Most demonstrated linear behavior if they were not located near one of the extremes of the dynamic range. Performance issues with any individual ERCC transcript could be attributed to detection limitations, platform-specific target probe issues, or potential mixing errors. Collectively, these pools of spike-in RNA controls were evaluated for suitability as surrogates for endogenous transcripts to interrogate the performance of the RNA measurement process of each platform. The controls were useful for establishing the dynamic range of the assay, as well as delineating the useable region of that range where differential expression measurements, expressed as ratios, would be expected to be accurate.
Conclusions: The modified Latin square design presented here uses a composite testing scheme for the evaluation of multiple performance characteristics: linear performance of individual controls, signal response within dynamic range pools of controls, and ratio detection between pairs of dynamic range pools. This compact design provides an economical sample format for the evaluation of multiple external RNA controls within a single experiment per platform. These results indicate that well-designed pools of RNA controls, spiked into samples, provide measurement assurance for endogenous gene expression studies.
C1 [Pine, P. Scott; Munro, Sarah A.; Parsons, Jerod R.; McDaniel, Jennifer; Salit, Marc] NIST, Joint Initiat Metrol Biol, 443 Via Ortega, Stanford, CA 94305 USA.
[Lucas, Anne Bergstrom] Agilent Technol, Genom Res & Dev, Santa Clara, CA 95051 USA.
[Lozach, Jean] Illumina Inc, San Diego, CA 92122 USA.
[Myers, Timothy G.; Su, Qin] NIAID, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Jacobs-Helber, Sarah M.] AIBioTech Inc, Richmond, VA 23235 USA.
[Jacobs-Helber, Sarah M.] GENETWORx LLC, Glen Allen, VA USA.
RP Pine, PS (reprint author), NIST, Joint Initiat Metrol Biol, 443 Via Ortega, Stanford, CA 94305 USA.
EM p.scott.pine@nist.gov
FU Intramural Research Program of the NIH, NIAID
FX This research was supported in part by the Intramural Research Program
of the NIH, NIAID.
NR 42
TC 1
Z9 1
U1 2
U2 2
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1472-6750
J9 BMC BIOTECHNOL
JI BMC Biotechnol.
PD JUN 24
PY 2016
VL 16
AR 54
DI 10.1186/s12896-016-0281-x
PG 15
WC Biotechnology & Applied Microbiology
SC Biotechnology & Applied Microbiology
GA DP6FB
UT WOS:000378591200003
PM 27342544
ER
PT J
AU Krushkal, J
Zhao, YD
Hose, C
Monks, A
Doroshow, JH
Simon, R
AF Krushkal, Julia
Zhao, Yingdong
Hose, Curtis
Monks, Anne
Doroshow, James H.
Simon, Richard
TI Concerted changes in transcriptional regulation of genes involved in DNA
methylation, demethylation, and folate-mediated one-carbon metabolism
pathways in the NCI-60 cancer cell line panel in response to cancer drug
treatment
SO CLINICAL EPIGENETICS
LA English
DT Article
DE Gene expression; DNA methylation; Folate metabolism; Cancer drug
treatment; Epigenetic analysis; NCI-60 cell lines
ID LUNG-CANCER; COLORECTAL-CANCER; PROSTATE-CANCER; OVARIAN-CANCER;
CISPLATIN RESISTANCE; BREAST-CANCER; HEPATOCELLULAR-CARCINOMA;
EXPRESSION SIGNATURES; 1-CARBON METABOLISM; METHYLTRANSFERASE
AB Background: Aberrant patterns of DNA methylation are abundant in cancer, and epigenetic pathways are increasingly being targeted in cancer drug treatment. Genetic components of the folate-mediated one-carbon metabolism pathway can affect DNA methylation and other vital cell functions, including DNA synthesis, amino acid biosynthesis, and cell growth.
Results: We used a bioinformatics tool, the Transcriptional Pharmacology Workbench, to analyze temporal changes in gene expression among epigenetic regulators of DNA methylation and demethylation, and one-carbon metabolism genes in response to cancer drug treatment. We analyzed gene expression information from the NCI-60 cancer cell line panel after treatment with five antitumor agents, 5-azacytidine, doxorubicin, vorinostat, paclitaxel, and cisplatin. Each antitumor agent elicited concerted changes in gene expression of multiple pathway components across the cell lines. Expression changes of FOLR2, SMUG1, GART, GADD45A, MBD1, MTR, MTHFD1, and CTH were significantly correlated with chemosensitivity to some of the agents. Among many genes with concerted expression response to individual antitumor agents were genes encoding DNA methyltransferases DNMT1, DNMT3A, and DNMT3B, epigenetic and DNA repair factors MGMT, GADD45A, and MBD1, and one-carbon metabolism pathway members MTHFD1, TYMS, DHFR, MTR, MAT2A, SLC19A1, ATIC, and GART.
Conclusions: These transcriptional changes are likely to influence vital cellular functions of DNA methylation and demethylation, cellular growth, DNA biosynthesis, and DNA repair, and some of them may contribute to cytotoxic and apoptotic action of the drugs. This concerted molecular response was observed in a time-dependent manner, which may provide future guidelines for temporal selection of genetic drug targets for combination drug therapy treatment regimens.
C1 [Krushkal, Julia; Zhao, Yingdong; Simon, Richard] NCI, Biometr Res Program, Div Canc Treatment & Diag, 9609 Med Ctr Dr, Rockville, MD 20850 USA.
[Hose, Curtis; Monks, Anne] Leidos Biomed Res Inc, Mol Pharmacol Grp, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
[Doroshow, James H.] NCI, Div Canc Treatment & Diag, Bethesda, MD 20892 USA.
RP Simon, R (reprint author), NCI, Biometr Res Program, Div Canc Treatment & Diag, 9609 Med Ctr Dr, Rockville, MD 20850 USA.
EM richard.simon@nih.gov
FU National Cancer Institute, National Institutes of Health
[HHSN261200800001E]; Developmental Therapeutics Program in the Division
of Cancer Treatment and Diagnosis of the National Cancer Institute
FX This project has been funded in part with federal funds from the
National Cancer Institute, National Institutes of Health, under Contract
No. HHSN261200800001E. The content of this publication does not
necessarily reflect the views or policies of the Department of Health
and Human Services, nor does mention of trade names, commercial
products, or organizations imply endorsement by the U.S. Government.
This research was supported [in part] by the Developmental Therapeutics
Program in the Division of Cancer Treatment and Diagnosis of the
National Cancer Institute.
NR 131
TC 0
Z9 0
U1 3
U2 3
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1868-7083
J9 CLIN EPIGENETICS
JI Clin. Epigenetics
PD JUN 24
PY 2016
VL 8
AR 73
DI 10.1186/s13148-016-0240-3
PG 24
WC Oncology
SC Oncology
GA DP6GN
UT WOS:000378595400001
PM 27347216
ER
PT J
AU Anson, ER
Bigelow, RT
Carey, JP
Xue, QL
Studenski, S
Schubert, MC
Agrawal, Y
AF Anson, Eric R.
Bigelow, Robin T.
Carey, John P.
Xue, Qian-Li
Studenski, Stephanie
Schubert, Michael C.
Agrawal, Yuri
TI VOR Gain Is Related to Compensatory Saccades in Healthy Older Adults
SO FRONTIERS IN AGING NEUROSCIENCE
LA English
DT Article
DE VOR; compensatory saccades; healthy aging; head impulse test; vestibular
ID HEAD IMPULSE TEST; CATCH-UP SACCADES; VESTIBULOOCULAR REFLEX;
VIDEO-OCULOGRAPHY; EYE-MOVEMENTS; DISORDERS; NYSTAGMUS; RESPONSES;
ACCURACY; SIGN
AB Objective: Vestibulo-ocular reflex (VOR) gain is well-suited for identifying rotational vestibular dysfunction, but may miss partial progressive decline in age-related vestibular function. Since compensatory saccades might provide an alternative method for identifying subtle vestibular decline, we describe the relationship between VOR gain and compensatory saccades in healthy older adults.
Methods: Horizontal VOR gain was measured in 243 subjects age 60 and older from the Baltimore Longitudinal Study of Aging using video head impulse testing (HIT). Saccades in each HIT were identified as either "compensatory" or "compensatory backup," i.e., same or opposite direction as the VOR response respectively. Saccades were also classified as "covert" (occurring during head movement) and "overt" (occurring after head movement). The relationship between VOR gain and percentage of HITs with saccades, as well as the relationship between VOR gain and saccade latency and amplitude, were evaluated using regression analyses adjusting for age, gender, and race.
Results: In adjusted analyses, the percentage of HITs with compensatory saccades increased 4.5% for every 0.1 decrease in VOR gain (p < 0.0001). Overt compensatory saccade amplitude decreased 0.6 (p 0.005) and latency increased 90 ms (p < 0.001) for every 0.1 increase in VOR gain. Covert back-up compensatory saccade amplitude increased 0.4 for every 0.1 increase in VOR gain.
Conclusion: We observed significant relationships between VOR gain and compensatory saccades in healthy older adults. Lower VOR gain was associated with larger amplitude, shorter latency compensatory saccades. Compensatory saccades reflect underlying rotational vestibular hypofunction, and may be particularly useful at identifying partial vestibular deficits as occur in aging adults.
C1 [Anson, Eric R.; Bigelow, Robin T.; Carey, John P.; Schubert, Michael C.; Agrawal, Yuri] Johns Hopkins Univ, Sch Med, Dept Otolaryngol Head & Neck Surg, Baltimore, MD 21205 USA.
[Xue, Qian-Li] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA.
[Xue, Qian-Li] Johns Hopkins Med Inst, Ctr Aging & Hlth, Baltimore, MD 21205 USA.
[Studenski, Stephanie] NIA, Longitudinal Studies Sect, Baltimore, MD 21224 USA.
RP Anson, ER (reprint author), Johns Hopkins Univ, Sch Med, Dept Otolaryngol Head & Neck Surg, Baltimore, MD 21205 USA.
EM eanson1@jhmi.edu
FU NIDCD [K23 DC013056, T32 DC000023]
FX Supported in part by NIDCD K23 DC013056 and NIDCD T32 DC000023.
NR 30
TC 1
Z9 1
U1 1
U2 3
PU FRONTIERS MEDIA SA
PI LAUSANNE
PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015,
SWITZERLAND
SN 1663-4365
J9 FRONT AGING NEUROSCI
JI Front. Aging Neurosci.
PD JUN 24
PY 2016
VL 8
AR 150
DI 10.3389/fnagi.2016.00150
PG 10
WC Geriatrics & Gerontology; Neurosciences
SC Geriatrics & Gerontology; Neurosciences & Neurology
GA DP5KJ
UT WOS:000378534800001
PM 27445793
ER
PT J
AU Zou, SM
Caler, L
Colombini-Hatch, S
Glynn, S
Srinivas, P
AF Zou, Shimian
Caler, Lis
Colombini-Hatch, Sandra
Glynn, Simone
Srinivas, Pothur
TI Research on the human virome: where are we and what is next
SO MICROBIOME
LA English
DT Article
DE Microbiome; Virome; Heart; Lung; Blood; HIV
ID PARVOVIRUS B19 INFECTION; BLOOD SAFETY; NATIONAL HEART; ENTERIC VIROME;
DISEASE; TRANSFUSION; VIRUSES; PROGRESS; DONOR; LUNG
AB The National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health convened a Working Group on the Microbiome in Cardiovascular, Pulmonary and Hematologic Health and Diseases from June 25, 2014, to June 26, 2014. The Working Group's central goal was to define what major microbiome research areas warranted additional study in the context of heart, lung, and blood (HLB) diseases. The Working Group identified studies of the human virome a key priority.
C1 [Zou, Shimian; Caler, Lis; Colombini-Hatch, Sandra; Glynn, Simone; Srinivas, Pothur] NHLBI, NIH, 6701,Rockledge Dr,Room 9144, Bethesda, MD 20892 USA.
RP Zou, SM (reprint author), NHLBI, NIH, 6701,Rockledge Dr,Room 9144, Bethesda, MD 20892 USA.
EM shimian.zou@nih.gov
NR 41
TC 1
Z9 1
U1 10
U2 16
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 2049-2618
J9 MICROBIOME
JI Microbiome
PD JUN 24
PY 2016
VL 4
AR 32
DI 10.1186/s40168-016-0177-y
PG 4
WC Microbiology
SC Microbiology
GA DP6QG
UT WOS:000378622000002
PM 27341799
ER
PT J
AU Hosseini-Vasoukolaei, N
Idali, F
Khamesipour, A
Yaghoobi-Ershadi, MR
Kamhawi, S
Valenzuela, JG
Edalatkhah, H
Arandian, MH
Mirhendi, H
Emami, S
Jafari, R
Saeidi, Z
Jeddi-Tehrani, M
Akhavan, AA
AF Hosseini-Vasoukolaei, Nasibeh
Idali, Farah
Khamesipour, Ali
Yaghoobi-Ershadi, Mohammad Reza
Kamhawi, Shaden
Valenzuela, Jesus G.
Edalatkhah, Haleh
Arandian, Mohammad Hossein
Mirhendi, Hossein
Emami, Shaghayegh
Jafari, Reza
Saeidi, Zahra
Jeddi-Tehrani, Mahmood
Akhavan, Amir Ahmad
TI Differential expression profiles of the salivary proteins SP15 and SP44
from Phlebotomus papatasi
SO PARASITES & VECTORS
LA English
DT Article
DE Salivary gene expression; Phlebotomus papatasi; PpSP15; PpSP44; Iran
ID ZOONOTIC CUTANEOUS LEISHMANIASIS; LUTZOMYIA-LONGIPALPIS COMPLEX;
SAND-FLY SALIVA; JORDAN VALLEY; VISCERAL LEISHMANIASIS; IMMUNE-RESPONSE;
GLAND PROTEINS; ENDEMIC AREA; CENTRAL IRAN; PSYCHODIDAE
AB Background: Sand fly saliva has been shown to help parasite establishment and to induce immune responses in vertebrate hosts. In the current study, we investigated the pattern of expression of two Phlebotomus papatasi salivary transcripts in specific physiological and seasonal conditions at a hyperendemic area of zoonotic cutaneous leishmaniasis (ZCL) in Iran.
Methods: Sand flies were collected during 2012-2013, and grouped according to physiological stages such as unfed, fed, semi-gravid, gravid, parous, nulliparous, infected or non-infected with Leishmania major and also based on the season in which they were collected. Quantitative Real-Time PCR was applied for assessment of the expression of two relevant salivary transcripts, PpSP15 and PpSP44, associated to protection from and exacerbation of ZCL, respectively.
Results: The expression of PpSP15 and PpSP44 transcripts was significantly up-regulated (1.74 and 1.4 folds, respectively) in blood fed compared to unfed flies. Among four groups of fed, unfed, semi-gravid and gravid flies, the lowest levels of PpSP15 and PpSP44 expression were observed in gravid flies. Additionally, the expression levels of both PpSP15 and PpSP44 transcripts in P. papatasi collected during summer were significantly up-regulated (3.7 and 4.4 folds, respectively) compared to spring collections. In addition, the PpSP15 transcript exhibited a significant up-regulation (P < 0.05) in non-infected flies compared to those infected with L. major.
Conclusions: This study contributes to our knowledge of the differential expression of salivary genes among different groups within a P. papatasi population under natural field conditions. Cutaneous and visceral leishmaniasis are of public health importance in many parts of Iran and neighbouring countries where P. papatasi is the proven and dominant sand fly vector for ZCL, the most prevalent and endemic form of the disease in Iran. Therefore, the current study could be helpful in understanding the influence of salivary genes on Leishmania transmission by phlebotomine sand flies. Our findings demonstrate the differential expression of salivary transcripts under various physiological conditions potentially influencing the sand fly capacity for parasite transmission as well as the outcome of disease.
C1 [Hosseini-Vasoukolaei, Nasibeh; Yaghoobi-Ershadi, Mohammad Reza; Saeidi, Zahra; Akhavan, Amir Ahmad] Univ Tehran Med Sci, Sch Publ Hlth, Dept Med Entomol & Vector Control, Tehran, Iran.
[Hosseini-Vasoukolaei, Nasibeh] Mazandaran Univ Med Sci, Fac Hlth, Dept Med Entomol & Vector Control, Hlth Sci Res Ctr, Sari, Iran.
[Idali, Farah] ACECR, Avicenna Res Inst, Reprod Immunol Res Ctr, Tehran, Iran.
[Khamesipour, Ali] Univ Tehran Med Sci, Ctr Res & Training Skin Dis & Leprosy, Tehran, Iran.
[Kamhawi, Shaden; Valenzuela, Jesus G.] NIAID, Vector Mol Biol Sect, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA.
[Edalatkhah, Haleh] ACECR, Avicenna Res Inst, Reprod Biotechnol Res Ctr, Tehran, Iran.
[Arandian, Mohammad Hossein; Jafari, Reza] Univ Tehran Med Sci, Natl Inst Hlth Res, Esfahan Hlth Res Stn, Esfahan, Iran.
[Mirhendi, Hossein] Isfahan Univ Med Sci, Sch Med, Dept Med Mycol & Parasitol, Esfahan, Iran.
[Emami, Shaghayegh; Jeddi-Tehrani, Mahmood] ACECR, Avicenna Res Inst, Monoclonal Antibody Res Ctr, Tehran, Iran.
RP Akhavan, AA (reprint author), Univ Tehran Med Sci, Sch Publ Hlth, Dept Med Entomol & Vector Control, Tehran, Iran.; Jeddi-Tehrani, M (reprint author), ACECR, Avicenna Res Inst, Monoclonal Antibody Res Ctr, Tehran, Iran.
EM mahjed@avicenna.ac.ir; aaakhavan@tums.ac.ir
FU Tehran University of Medical Sciences (TUMS) [18511/16.5.2012]; Avicenna
Research Institute; ACECR [910206-018]
FX This work was supported by Research deputy of Tehran University of
Medical Sciences (TUMS), Project No. 18511/16.5.2012 and Avicenna
Research Institute, ACECR, Project No. 910206-018. We thank Dr. Shabani
for his helpful comments, Ms. Babaei, Ms. Balaei and Mr. Hadavi for
their technical support, from Avicenna Research Institute, ACECR. We are
very grateful to Ms. Shareghi, Esfahan Health Research Station, National
Institute of Health Research, TUMS, for her assistance in the project.
We are grateful to Ms. Ahmadi and Ms. Bolandian, School of Public
Health, TUMS, for their assistance in sand fly rearing.
NR 46
TC 0
Z9 0
U1 1
U2 1
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1756-3305
J9 PARASITE VECTOR
JI Parasites Vectors
PD JUN 24
PY 2016
VL 9
AR 357
DI 10.1186/s13071-016-1633-z
PG 10
WC Parasitology
SC Parasitology
GA DP9RC
UT WOS:000378833500001
PM 27342811
ER
PT J
AU Long, MT
Pedley, A
Massaro, JM
Hoffmann, U
Fox, CS
AF Long, Michelle T.
Pedley, Alison
Massaro, Joseph M.
Hoffmann, Udo
Fox, Caroline S.
TI The Association between Non-Invasive Hepatic Fibrosis Markers and
Cardiometabolic Risk Factors in the Framingham Heart Study
SO PLOS ONE
LA English
DT Article
ID FATTY LIVER-DISEASE; INCREASED ARTERIAL STIFFNESS; PULSE PRESSURE;
NONALCOHOLIC STEATOHEPATITIS; DIAGNOSIS; BIOPSY; ADULTS
AB Background & Aims
Non-alcoholic fatty liver disease (NAFLD) is associated with an increased risk of cardiovascular related death, particularly in those with hepatic fibrosis. We determined the prevalence of predicted fibrosis based on non-invasive fibrosis markers and the association of hepatic fibrosis with cardiovascular risk factors.
Methods
Cross-sectional study of 575 Framingham Heart Study participants with NAFLD based on computed tomography. We determined the prevalence of predicted fibrosis based on the aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio, AST to platelet ratio index (APRI), the Fibrosis-4 score (FIB4), and the NAFLD Fibrosis Score (NFS). Using multivariable logistic regression models, we examined the association between low, indeterminate, or high risk for fibrosis according to the NFS and various cardiometabolic risk factors.
Results
The predicted risk of fibrosis was 12%, 4%, 5%, and 32% for the NFS, FIB4, APRI, and AST/ALT ratio, respectively. In multivariable models, participants with a high risk for advanced fibrosis by the NFS had a wider pulse pressure (adjusted mean difference = 6.87 mm Hg; p = 0.0002) and an increased odds of hypertension (OR 2.92; p = 0.007) compared to those with low risk of fibrosis. There were no statistically significant differences between other cardiovascular risk factors for those with a high versus low risk of fibrosis.
Conclusions
The AST/ALT ratio, APRI, and NFS give widely disparate predictions of liver fibrosis. Participants with a high risk for fibrosis based on NFS had wider pulse pressure and increased odds of hypertension. Whether modifying these risk factors impacts cardiovascular endpoints in NAFLD patients remains unknown.
C1 [Long, Michelle T.] Boston Univ, Sch Med, Div Gastroenterol, Boston Med Ctr, Boston, MA 02118 USA.
[Long, Michelle T.; Pedley, Alison; Massaro, Joseph M.; Fox, Caroline S.] NHLBI, Framingham Heart Study, Framingham, MA USA.
[Pedley, Alison] Merck Res Labs, Kenilworth, NJ USA.
[Massaro, Joseph M.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA.
[Hoffmann, Udo] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA.
[Fox, Caroline S.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Endocrinol Hypertens & Metab, Boston, MA 02115 USA.
RP Long, MT (reprint author), Boston Univ, Sch Med, Div Gastroenterol, Boston Med Ctr, Boston, MA 02118 USA.; Long, MT (reprint author), NHLBI, Framingham Heart Study, Framingham, MA USA.
EM mtlong@bu.edu
OI Long, Michelle/0000-0001-6131-3981
FU Boston University School of Medicine; National Heart, Lung, and Blood
Institute's Framingham Heart Study [N01-HC-25195, HHSN268201500001I];
Division of Intramural Research of the National Heart, Lung, and Blood
Institute
FX This work was supported by the Boston University School of Medicine and
the National Heart, Lung, and Blood Institute's Framingham Heart Study
(contract N01-HC-25195 and HHSN268201500001I), and the Division of
Intramural Research of the National Heart, Lung, and Blood Institute.
The funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript. Alison Pedley is
an employee of Merck. The funder provided support in the form of
salaries for authors [AP], but did not have any additional role in the
study design, data collection and analysis, decision to publish, or
preparation of the manuscript. The specific roles of these authors are
articulated in the 'author contributions' section.
NR 31
TC 2
Z9 2
U1 2
U2 3
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUN 24
PY 2016
VL 11
IS 6
AR e0157517
DI 10.1371/journal.pone.0157517
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DP3KZ
UT WOS:000378393600008
PM 27341207
ER
PT J
AU Heman-Ackah, SM
Bassett, AR
Wood, MJA
AF Heman-Ackah, Sabrina Mahalia
Bassett, Andrew Roger
Wood, Matthew John Andrew
TI Precision Modulation of Neurodegenerative Disease-Related Gene
Expression in Human iPSC-Derived Neurons
SO SCIENTIFIC REPORTS
LA English
DT Article
ID PLURIPOTENT STEM-CELLS; ALPHA-SYNUCLEIN LOCUS; FAMILIAL
PARKINSONS-DISEASE; ALZHEIMERS-DISEASE; LEWY BODIES; CAS9; CRISPR;
SPECIFICITY; ACTIVATION; DEMENTIA
AB The ability to reprogram adult somatic cells into induced pluripotent stem cells (iPSCs) and the subsequent development of protocols for their differentiation into disease-relevant cell types have enabled in-depth molecular analyses of multiple disease states as hitherto impossible. Neurons differentiated from patient-specific iPSCs provide a means to recapitulate molecular phenotypes of neurodegenerative diseases in vitro. However, it remains challenging to conduct precise manipulations of gene expression in iPSC-derived neurons towards modeling complex human neurological diseases. The application of CRISPR/Cas9 to mammalian systems is revolutionizing the utilization of genome editing technologies in the study of molecular contributors to the pathogenesis of numerous diseases. Here, we demonstrate that CRISPRa and CRISPRi can be used to exert precise modulations of endogenous gene expression in fate-committed iPSC-derived neurons. This highlights CRISPRa/i as a major technical advancement in accessible tools for evaluating the specific contributions of critical neurodegenerative disease-related genes to neuropathogenesis.
C1 [Heman-Ackah, Sabrina Mahalia; Wood, Matthew John Andrew] Univ Oxford, Dept Physiol Anat & Genet, Oxford OX1 3QX, England.
[Heman-Ackah, Sabrina Mahalia] NIH, NIH Oxford Cambridge Scholars Program, Bldg 10, Bethesda, MD 20892 USA.
[Heman-Ackah, Sabrina Mahalia] Univ N Carolina, UNC MD PhD Program, Chapel Hill, NC 27599 USA.
[Bassett, Andrew Roger] Univ Oxford, Sir William Dunn Sch Pathol, Genome Engn Oxford, S Parks Rd, Oxford OX1 3RE, England.
[Bassett, Andrew Roger] Wellcome Trust Sanger Inst, Wellcome Genome Campus, Cambridge CB10 1SA, England.
RP Heman-Ackah, SM (reprint author), Univ Oxford, Dept Physiol Anat & Genet, Oxford OX1 3QX, England.; Heman-Ackah, SM (reprint author), NIH, NIH Oxford Cambridge Scholars Program, Bldg 10, Bethesda, MD 20892 USA.; Heman-Ackah, SM (reprint author), Univ N Carolina, UNC MD PhD Program, Chapel Hill, NC 27599 USA.
EM hemanackah.sabrina@gmail.com
FU NIH Oxford-Cambridge Scholars Program; University of North Carolina at
Chapel Hill MD-PhD Program; Oxford University John Fell Fund; Cure
Parkinson's Trust; Wellcome Trust Institutional Strategic Support Fund
(ISSF)
FX The authors would like to thank Wilfried Haerty for help with analysis
of CAGE data and Natasha Gromak and Nick Proudfoot for helpful
discussions. We would also like to acknowledge the NIH Center for
Regenerative Medicine (NIH CRM) for providing valuable study materials,
including NCRM-1 (NIH CRM), NCRM-5 (NIH CRM), ND34391G (Coriell) and
ND38477C (Coriell) iPSCs and NCRM-5 iPSC-derived NSCs. NHDF-1 iPSCs were
a kind gift from Sally Cowley of the James Martin Stem Cell Facility.
The pAC154-dual-dCas9VP160-sgExpression vector was a gift from Rudolf
Jaenisch (Addgene #48240), and the SP-dCas9-VPR vector was a gift from
George Church (Addgene #63798). S.M.H.-A. is supported by the NIH
Oxford-Cambridge Scholars Program and the University of North Carolina
at Chapel Hill MD-PhD Program. Awards to S.M.H.-A. and M.J.A.W. from the
Oxford University John Fell Fund and Cure Parkinson's Trust provided
core support for this project. Awards to A.R.B. from the Oxford
University John Fell Fund and Wellcome Trust Institutional Strategic
Support Fund (ISSF) further supported the work presented in this
manuscript.
NR 58
TC 2
Z9 2
U1 4
U2 5
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2045-2322
J9 SCI REP-UK
JI Sci Rep
PD JUN 24
PY 2016
VL 6
AR 28420
DI 10.1038/srep28420
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DP4QF
UT WOS:000378479900001
PM 27341390
ER
PT J
AU Devambatla, RKV
Namjoshi, OA
Choudhary, S
Hamel, E
Shaffer, CV
Rohena, CC
Mooberry, SL
Gangjee, A
AF Devambatla, Ravi Kumar Vyas
Namjoshi, Ojas A.
Choudhary, Shruti
Hamel, Ernest
Shaffer, Corena V.
Rohena, Cristina C.
Mooberry, Susan L.
Gangjee, Aleem
TI Design, Synthesis, and Preclinical Evaluation of
4-Substituted-5-methyl-furo[2,3-d]pyrimidines as Microtubule Targeting
Agents That Are Effective against Multidrug Resistant Cancer Cells
SO JOURNAL OF MEDICINAL CHEMISTRY
LA English
DT Article
ID III BETA-TUBULIN; COMBRETASTATIN A4 PHOSPHATE; I CLINICAL-TRIAL;
BREAST-CANCER; LUNG-CANCER; COLCHICINE SITE; OVARIAN-CANCER;
BINDING-SITE; ANTICANCER DRUGS; ANTITUMOR AGENTS
AB The design, synthesis, and biological evaluations of eight 4-substituted 5-methyl-furo[2,3-d]pyrimidines are reported. Synthesis involved N-4-alkylation of N-aryl-5-methylfuro[2,3-d]pyrimidin-4-amines, obtained from Ullmann coupling of 4-amino-5-methylfuro[2,3-d]pyrimidine and appropriate aryl iodides. Compounds 3, 4, and 9 showed potent microtubule depolymerizing activities, while compounds 6-8 had slightly lower potency. Compounds 4, 6, 7, and 9 inhibited tubulin assembly with IC50 values comparable to that of combretastatin A-4 (CA-4). Compounds 3, 4, and 6-9 circumvented Pgp and beta III-tubulin mediated drug resistance, mechanisms that can limit the efficacy of paclitaxel, docetaxel, and the vinca alkaloids. In the NCI 60-cell line panel, compound 3 exhibited GI(50) values less than 10 nM in 47 of the cell lines. In an MDA-MB-435 xenograft model, compound 3 had statistically significant antitumor effects. The biological effects of 3 identify it as a novel, potent microtubule depolymerizing agent with antitumor activity.
C1 [Devambatla, Ravi Kumar Vyas; Namjoshi, Ojas A.; Choudhary, Shruti; Gangjee, Aleem] Duquesne Univ, Grad Sch Pharmaceut Sci, Div Med Chem, 600 Forbes Ave, Pittsburgh, PA 15282 USA.
[Shaffer, Corena V.; Rohena, Cristina C.; Mooberry, Susan L.] Univ Texas Hlth Sci Ctr San Antonio, Canc Therapy & Res Ctr, Dept Pharmacol, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA.
[Hamel, Ernest] NCI, Screening Technol Branch,Dev Therapeut Program, Div Canc Treatment & Diag,Frederick Natl Lab Canc, NIH, Frederick, MD 21702 USA.
[Namjoshi, Ojas A.] RTI Int, Ctr Drug Discovery, 3040 E Cornwallis Rd, Res Triangle Pk, NC 27709 USA.
RP Gangjee, A (reprint author), Duquesne Univ, Grad Sch Pharmaceut Sci, Div Med Chem, 600 Forbes Ave, Pittsburgh, PA 15282 USA.
EM mooberry@uthscsa.edu; gangjee@duq.edu
FU National Institutes of Health, National Cancer Institute [CA142868];
President's Council Research Excellence Award; Duquesne University
Adrian Van Kaam Chair in Scholarly Excellence; CTRC Cancer Center
Support Grant [P30 CA054174]; Flow Cytometry Shared Resource; NSF [NMR:
CHE 0614785]
FX We acknowledge the National Cancer Institute Developmental Therapeutics
Program for performing the in vitro evaluation in the NCI 60-cell line
panel. This work was supported, in part, by a grant from the National
Institutes of Health, National Cancer Institute (CA142868 (to A.G.,
S.L.M.)); by the President's Council Research Excellence Award (to
S.L.M.), Duquesne University Adrian Van Kaam Chair in Scholarly
Excellence (to A.G.); the CTRC Cancer Center Support Grant P30 CA054174
and the Flow Cytometry Shared Resource; and by an NSF equipment grant
for NMR instrumentation (NMR: CHE 0614785). We thank Mr. Arpit Doshi,
Duquesne University, for the NMR analysis of compound 2.
NR 51
TC 2
Z9 2
U1 14
U2 19
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0022-2623
EI 1520-4804
J9 J MED CHEM
JI J. Med. Chem.
PD JUN 23
PY 2016
VL 59
IS 12
BP 5752
EP 5765
DI 10.1021/acs.jmedchem.6b00237
PG 14
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA DP7EV
UT WOS:000378662900012
PM 27213719
ER
PT J
AU Domanova, W
Krycer, J
Chaudhuri, R
Yang, PY
Vafaee, F
Fazakerley, D
Humphrey, S
James, D
Kuncic, Z
AF Domanova, Westa
Krycer, James
Chaudhuri, Rima
Yang, Pengyi
Vafaee, Fatemeh
Fazakerley, Daniel
Humphrey, Sean
James, David
Kuncic, Zdenka
TI Unraveling Kinase Activation Dynamics Using Kinase-Substrate
Relationships from Temporal Large-Scale Phosphoproteomics Studies
SO PLOS ONE
LA English
DT Article
ID INSULIN-RESISTANCE; ELONGATION-FACTOR-2 KINASE; PHOSPHORYLATION
NETWORKS; PROTEIN; REVEALS; PATTERNS; SURVIVAL; DATABASE; COMPLEX; SITES
AB In response to stimuli, biological processes are tightly controlled by dynamic cellular signaling mechanisms. Reversible protein phosphorylation occurs on rapid time-scales (milliseconds to seconds), making it an ideal carrier of these signals. Advances in mass spectrometry-based proteomics have led to the identification of many tens of thousands of phosphorylation sites, yet for the majority of these the kinase is unknown and the underlying network topology of signaling networks therefore remains obscured. Identifying kinase substrate relationships (KSRs) is therefore an important goal in cell signaling research. Existing consensus sequence motif based prediction algorithms do not consider the biological context of KSRs, and are therefore insensitive to many other mechanisms guiding kinase-substrate recognition in cellular contexts. Here, we use temporal information to identify biologically relevant KSRs from Large-scale In Vivo Experiments (KSR-LIVE) in a data-dependent and automated fashion. First, we used available phosphorylation databases to construct a repository of existing experimentally-predicted KSRs. For each kinase in this database, we used time-resolved phosphoproteomics data to examine how its substrates changed in phosphorylation over time. Although substrates for a particular kinase clustered together, they often exhibited a different temporal pattern to the phosphorylation of the kinase. Therefore, although phosphorylation regulates kinase activity, our findings imply that substrate phosphorylation likely serve as a better proxy for kinase activity than kinase phosphorylation. KSR-LIVE can thereby infer which kinases are regulated within a biological context. Moreover, KSR-LIVE can also be used to automatically generate positive training sets for the subsequent prediction of novel KSRs using machine learning approaches. We demonstrate that this approach can distinguish between Akt and Rps6kb1, two kinases that share the same linear consensus motif, and provide evidence suggesting IRS-1 S265 as a novel Akt site. KSR-LIVE is an open-access algorithm that allows users to dissect phosphorylation signaling within a specific biological context, with the potential to be included in the standard analysis workflow for studying temporal high-throughput signal transduction data.
C1 [Domanova, Westa; Krycer, James; Chaudhuri, Rima; Vafaee, Fatemeh; Fazakerley, Daniel; James, David; Kuncic, Zdenka] Univ Sydney, Charles Perkins Ctr, Sydney, NSW 2006, Australia.
[Domanova, Westa; Kuncic, Zdenka] Univ Sydney, Sch Phys, Sydney, NSW 2006, Australia.
[Krycer, James; Chaudhuri, Rima; Fazakerley, Daniel; James, David] Univ Sydney, Sch Life & Environm Sci, Sydney, NSW 2006, Australia.
[Yang, Pengyi] NIEHS, NIH, Durham, NC 27709 USA.
[Vafaee, Fatemeh] Univ Sydney, Sch Math & Stat, Sydney, NSW 2006, Australia.
[Humphrey, Sean] Max Planck Inst Biochem, Dept Prote & Signal Transduct, Klopferspitz 18A, D-82152 Martinsried, Germany.
[James, David] Univ Sydney, Sydney Med Sch, Sydney, NSW 2006, Australia.
RP James, D; Kuncic, Z (reprint author), Univ Sydney, Charles Perkins Ctr, Sydney, NSW 2006, Australia.; Kuncic, Z (reprint author), Univ Sydney, Sch Phys, Sydney, NSW 2006, Australia.; James, D (reprint author), Univ Sydney, Sch Life & Environm Sci, Sydney, NSW 2006, Australia.; James, D (reprint author), Univ Sydney, Sydney Med Sch, Sydney, NSW 2006, Australia.
EM david.james@sydney.edu.au; zdenka.kuncic@sydney.edu.au
OI Yang, Pengyi/0000-0003-1098-3138
FU NHMRC [GNT1061122]; Australian Postgraduate Award scholarship
FX This work is supported by the NHMRC (project grant GNT1061122). DJ is an
NHMRC Senior Principal Research Fellow. JK is an NHMRC Early Career
Fellow. WD is supported by an Australian Postgraduate Award scholarship.
NR 42
TC 1
Z9 1
U1 8
U2 12
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUN 23
PY 2016
VL 11
IS 6
AR e0157763
DI 10.1371/journal.pone.0157763
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DP3JL
UT WOS:000378389200041
PM 27336693
ER
PT J
AU Ho, R
Siddiqui, MM
George, AK
Frye, T
Kilchevsky, A
Fascelli, M
Shakir, NA
Chelluri, R
Abboud, SF
Walton-Diaz, A
Sankineni, S
Merino, MJ
Turkbey, B
Choyke, PL
Wood, BJ
Pinto, PA
AF Ho, Richard
Siddiqui, Mohummad M.
George, Arvin K.
Frye, Thomas
Kilchevsky, Amichai
Fascelli, Michele
Shakir, Nabeel A.
Chelluri, Raju
Abboud, Steven F.
Walton-Diaz, Annerleim
Sankineni, Sandeep
Merino, Maria J.
Turkbey, Baris
Choyke, Peter L.
Wood, Bradford J.
Pinto, Peter A.
TI Preoperative Multiparametric Magnetic Resonance Imaging Predicts
Biochemical Recurrence in Prostate Cancer after Radical Prostatectomy
SO PLOS ONE
LA English
DT Article
ID ANTIGEN RECURRENCE; OUTCOMES; RISK; GUIDELINES; MORTALITY; FAILURE;
UTILITY; BIOPSY; MRI
AB Objectives
To evaluate the utility of preoperative multiparametric magnetic resonance imaging (MP-MRI) in predicting biochemical recurrence (BCR) following radical prostatectomy (RP).
Materials/Methods
From March 2007 to January 2015, 421 consecutive patients with prostate cancer (PCa) underwent preoperative MP-MRI and RP. BCR-free survival rates were estimated using the Kaplan-Meier method. Cox proportional hazards models were used to identify clinical and imaging variables predictive of BCR. Logistic regression was performed to generate a nomogram to predict three-year BCR probability.
Results
Of the total cohort, 370 patients met inclusion criteria with 39 (10.5%) patients experiencing BCR. On multivariate analysis, preoperative prostate-specific antigen (PSA) (p = 0.01), biopsy Gleason score (p = 0.0008), MP-MRI suspicion score (p = 0.03), and extracapsular extension on MP-MRI (p = 0.03) were significantly associated with time to BCR. A nomogram integrating these factors to predict BCR at three years after RP demonstrated a c-index of 0.84, outperforming the predictive value of Gleason score and PSA alone (c-index 0.74, p = 0.02).
Conclusion
The addition of MP-MRI to standard clinical factors significantly improves prediction of BCR in a post-prostatectomy PCa cohort. This could serve as a valuable tool to support clinical decision-making in patients with moderate and high-risk cancers.
C1 [Ho, Richard; Siddiqui, Mohummad M.; George, Arvin K.; Frye, Thomas; Kilchevsky, Amichai; Fascelli, Michele; Shakir, Nabeel A.; Chelluri, Raju; Abboud, Steven F.; Walton-Diaz, Annerleim; Pinto, Peter A.] NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA.
[Sankineni, Sandeep; Turkbey, Baris; Choyke, Peter L.] NCI, Mol Imaging Program, NIH, Bethesda, MD 20892 USA.
[Merino, Maria J.] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA.
[Wood, Bradford J.] NCI, Ctr Intervent Oncol, NIH, Bethesda, MD 20892 USA.
[Siddiqui, Mohummad M.] Univ Maryland, Dept Surg, Div Urol, Baltimore, MD 21201 USA.
RP Pinto, PA (reprint author), NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA.
EM pintop@mail.nih.gov
OI Ho, Richard/0000-0002-6792-3411
FU Center for Cancer Research; Center for Interventional Oncology; NIH;
Intramural Research Program of the National Institutes of Health,
National Cancer Institute; Pfizer Inc.; Doris Duke Charitable
Foundation; Alexandria Real Estate Equities, Inc.; Howard Hughes Medical
Institute
FX This research was supported by the Intramural Research Program of the
National Institutes of Health, National Cancer Institute, the Center for
Cancer Research, and the Center for Interventional Oncology. NIH and
Philips Healthcare/Invivo Corp. have a cooperative research and
development agreement. NIH and Philips share intellectual property in
the field. This research was also made possible through the National
Institutes of Health Medical Research Scholars Program, a public-private
partnership supported jointly by the NIH and generous contributions to
the Foundation for the NIH from Pfizer Inc., The Doris Duke Charitable
Foundation, The Alexandria Real Estate Equities, Inc. and Mr. and Mrs.
Joel S. Marcus, and the Howard Hughes Medical Institute, as well as
other private donors. For a complete list, please visit the Foundation
website at:
http://fnih.org/what-we-do/current-education-and-training-programs/mrsp.
The funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 31
TC 1
Z9 1
U1 2
U2 2
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUN 23
PY 2016
VL 11
IS 6
AR e0157313
DI 10.1371/journal.pone.0157313
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DP3JL
UT WOS:000378389200015
PM 27336392
ER
PT J
AU Malachowa, N
Kobayashi, SD
Porter, AR
Braughton, KR
Scott, DP
Gardner, DJ
Missiakas, DM
Schneewind, O
Deleo, FR
AF Malachowa, Natalia
Kobayashi, Scott D.
Porter, Adeline R.
Braughton, Kevin R.
Scott, Dana P.
Gardner, Donald J.
Missiakas, Dominique M.
Schneewind, Olaf
Deleo, Frank R.
TI Contribution of Staphylococcus aureus Coagulases and Clumping Factor A
to Abscess Formation in a Rabbit Model of Skin and Soft Tissue Infection
SO PLOS ONE
LA English
DT Article
ID FACTOR-BINDING-PROTEIN; INTRAVENOUS INJECTION; VASCULAR-PERMEABILITY;
CUTANEOUS INFECTIONS; IMMUNE-RESPONSES; MOUSE MODEL; FACTOR-I;
VIRULENCE; SURFACE; ROLES
AB Staphylococcus aureus produces numerous factors that facilitate survival in the human host. S. aureus coagulase (Coa) and von Willebrand factor-binding protein (vWbp) are known to clot plasma through activation of prothrombin and conversion of fibrinogen to fibrin. In addition, S. aureus clumping factor A (ClfA) binds fibrinogen and contributes to platelet aggregation via a fibrinogen-or complement-dependent mechanism. Here, we evaluated the contribution of Coa, vWbp and ClfA to S. aureus pathogenesis in a rabbit model of skin and soft tissue infection. Compared to skin abscesses caused by the Newman wild-type strain, those caused by isogenic coa, vwb, or clfA deletion strains, or a strain deficient in coa and vwb, were significantly smaller following subcutaneous inoculation in rabbits. Unexpectedly, we found that fibrin deposition and abscess capsule formation appear to be independent of S. aureus coagulase activity in the rabbit infection model. Similarities notwithstanding, S. aureus strains deficient in coa and vwb elicited reduced levels of several proinflammatory molecules in human blood in vitro. Although a specific mechanism remains to be determined, we conclude that S. aureus Coa, vWbp and ClfA contribute to abscess formation in rabbits.
C1 [Malachowa, Natalia; Kobayashi, Scott D.; Porter, Adeline R.; Braughton, Kevin R.; Deleo, Frank R.] NIAID, Bacteriol Lab, Rocky Mt Labs, NIH, Hamilton, MT USA.
[Scott, Dana P.; Gardner, Donald J.] NIAID, Rocky Mt Vet Branch, Rocky Mt Labs, NIH, Hamilton, MT USA.
[Missiakas, Dominique M.; Schneewind, Olaf] Univ Chicago, Dept Microbiol, Chicago, IL 60637 USA.
RP Deleo, FR (reprint author), NIAID, Bacteriol Lab, Rocky Mt Labs, NIH, Hamilton, MT USA.
EM fdeleo@niaid.nih.gov
OI DeLeo, Frank/0000-0003-3150-2516
FU Intramural Research Program of the National Institute of Allergy and
Infectious Diseases, National Institutes of Health
FX Support was provided by Intramural Research Program of the National
Institute of Allergy and Infectious Diseases, National Institutes of
Health.
NR 53
TC 1
Z9 1
U1 2
U2 4
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUN 23
PY 2016
VL 11
IS 6
AR e0158293
DI 10.1371/journal.pone.0158293
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DP3JL
UT WOS:000378389200129
PM 27336691
ER
PT J
AU Spensieri, F
Siena, E
Borgogni, E
Zedda, L
Cantisani, R
Chiappini, N
Schiavetti, F
Rosa, D
Castellino, F
Montomoli, E
Bodinham, CL
Lewis, DJ
Medini, D
Bertholet, S
Del Giudice, G
AF Spensieri, Fabiana
Siena, Emilio
Borgogni, Erica
Zedda, Luisanna
Cantisani, Rocco
Chiappini, Nico
Schiavetti, Francesca
Rosa, Domenico
Castellino, Flora
Montomoli, Emanuele
Bodinham, Caroline L.
Lewis, David J.
Medini, Duccio
Bertholet, Sylvie
Del Giudice, Giuseppe
TI Early Rise of Blood T Follicular Helper Cell Subsets and Baseline
Immunity as Predictors of Persisting Late Functional Antibody Responses
to Vaccination in Humans
SO PLOS ONE
LA English
DT Article
ID CXC CHEMOKINE RECEPTOR-5; MEMORY TFH CELLS; GERMINAL-CENTERS; H1N1
VACCINE; B-CELLS; INFLUENZA; EXPRESSION; NONRESPONDERS; CORRELATE; TRIAL
AB CD4(+) T follicular helper cells (T-FH) have been identified as the T-cell subset specialized in providing help to B cells for optimal activation and production of high affinity antibody. We recently demonstrated that the expansion of peripheral blood influenza-specific CD4(+) IL-21(+) ICOS1(+) T helper (T-H) cells, three weeks after vaccination, associated with and predicted the rise of protective neutralizing antibodies to avian H5N1. In this study, healthy adults were vaccinated with plain seasonal trivalent inactivated influenza vaccine (TIIV), MF59 (R)-adjuvanted TIIV (ATIIV), or saline placebo. Frequencies of circulating CD4(+) T(FH)1 ICOS+ T-FH cells and H1N1-specific CD4(+-) IL-21(+) ICOS+ CXCR5(+) T-FH and CXCR5-T-H cell subsets were determined at various time points after vaccination and were then correlated with hemagglutination inhibition (HI) titers. All three CD4(+) T cell subsets expanded in response to TIIV and ATIIV, and peaked 7 days after vaccination. To demonstrate that these T-FH cell subsets correlated with functional antibody titers, we defined an alternative endpoint metric, decorrelated HI (DHI), which removed any correlation between day 28/day 168 and day 0 HI titers, to control for the effect of preexisting immunity to influenza vaccine strains. The numbers of total circulating CD4(+) T(FH)1 ICOS+ cells and of H1N1-specific CD4(+)IL-21(+)ICOS(+)CXCR5(+), measured at day 7, were significantly associated with day 28, and day 28 and 168 DHI titers, respectively. Altogether, our results show that CD4(+) T-FH subsets may represent valuable biomarkers of vaccine-induced long-term functional immunity.
C1 [Spensieri, Fabiana; Siena, Emilio; Borgogni, Erica; Zedda, Luisanna; Cantisani, Rocco; Chiappini, Nico; Schiavetti, Francesca; Rosa, Domenico; Castellino, Flora; Medini, Duccio; Bertholet, Sylvie; Del Giudice, Giuseppe] Novartis Vaccines & Diagnost Srl, Siena, Italy.
[Montomoli, Emanuele] Univ Siena, Dept Mol & Dev Med, Siena, Italy.
[Montomoli, Emanuele] VisMederi Srl, Siena, Italy.
[Bodinham, Caroline L.; Lewis, David J.] Univ Surrey, Surrey Clin Res Ctr, Guildford GU2 5XH, Surrey, England.
[Spensieri, Fabiana; Siena, Emilio; Borgogni, Erica; Zedda, Luisanna; Chiappini, Nico; Schiavetti, Francesca; Rosa, Domenico; Medini, Duccio; Bertholet, Sylvie; Del Giudice, Giuseppe] GSK Vaccines Srl, Siena, Italy.
[Cantisani, Rocco] Univ Hosp, Lab Immunohematol, Pisa, Italy.
[Castellino, Flora] NHLBI, Ctr Human Immunol, NIH, Bldg 10, Bethesda, MD 20892 USA.
RP Bertholet, S (reprint author), Novartis Vaccines & Diagnost Srl, Siena, Italy.; Bertholet, S (reprint author), GSK Vaccines Srl, Siena, Italy.
EM sylvie.c.bertholet-girardin@gsk.com
RI Medini, Duccio/Q-9556-2016
OI Medini, Duccio/0000-0001-6041-2603
FU Innovative Medicines Initiative Joint Undertaking [115308]; European
Union's Seventh Framework Programme; EFPIA companies'
FX These studies were funded by the Innovative Medicines Initiative Joint
Undertaking under grant agreement no. 115308, resources of which are
composed of financial contribution from the European Union's Seventh
Framework Programme (FP7/2007-2013) and EFPIA companies' in kind
contribution. The funders had no role in study design, data collection
and analysis, decision to publish, or preparation of the manuscript.
NR 33
TC 1
Z9 1
U1 1
U2 1
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUN 23
PY 2016
VL 11
IS 6
AR e0157066
DI 10.1371/journal.pone.0157066
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DP3JL
UT WOS:000378389200009
PM 27336786
ER
PT J
AU Roschewski, M
Roschewski, M
Staudt, LM
Wilson, WH
AF Roschewski, Mark
Roschewski, Mark
Staudt, Louis M.
Wilson, Wyndham H.
TI Dynamic monitoring of circulating tumor DNA in non-Hodgkin lymphoma
SO BLOOD
LA English
DT Article
ID B-CELL LYMPHOMA; MINIMAL RESIDUAL DISEASE; CANCER-PATIENTS; FOLLICULAR
LYMPHOMA; PROGNOSTIC VALUE; FDG-PET; THERAPY; REMISSION; BLOOD; CT
AB Response assessment in lymphoma relies on imaging scans that do not capture biologic processes at the molecular level. Monitoring circulating tumor DNA(ctDNA) with next-generation sequencing-based assays can detect recurrent disease prior to scans and "liquid biopsies" for somatic mutations address tumor heterogeneity, clonal evolution, and mechanisms of resistance to guide precision treatment. Preanalytic collection and processing procedures should be validated and standardized. We describe emerging applications of ctDNA monitoring including real-time analysis of tumor dynamics, preclinical disease detection, and precision-directed treatment paradigms.
C1 [Roschewski, Mark; Roschewski, Mark; Staudt, Louis M.; Wilson, Wyndham H.] NCI, Lymphoid Malignancies Branch, Ctr Canc Res, NIH, 9000 Rockville Pike,Bldg 10,Room 4N-115, Bethesda, MD 20892 USA.
RP Roschewski, M (reprint author), NCI, Lymphoid Malignancies Branch, Ctr Canc Res, NIH, 9000 Rockville Pike,Bldg 10,Room 4N-115, Bethesda, MD 20892 USA.
EM mark.roschewski@nih.gov
FU National Institutes of Health
FX We acknowledge support from the intramural research program of the
National Institutes of Health, especially Kieron Dunleavy and the
research team. Alan Hoofring and S. Peter Wu are acknowledged for
illustration support.
NR 44
TC 5
Z9 5
U1 7
U2 15
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA
SN 0006-4971
EI 1528-0020
J9 BLOOD
JI Blood
PD JUN 23
PY 2016
VL 127
IS 25
BP 3127
EP 3132
DI 10.1182/blood-2016-03-635219
PG 6
WC Hematology
SC Hematology
GA DP2RK
UT WOS:000378337700006
PM 27081097
ER
PT J
AU Toubiana, J
Okada, S
Hiller, J
Oleastro, M
Gomez, ML
Becerra, JCA
Ouachee-Chardin, M
Fouyssac, F
Girisha, KM
Etzioni, A
Van Montfrans, J
Camcioglu, Y
Kerns, LA
Belohradsky, B
Blanche, S
Bousfiha, A
Rodriguez-Gallego, C
Meyts, I
Kisand, K
Reichenbach, J
Renner, ED
Rosenzweig, S
Grimbacher, B
van de Veerdonk, FL
Traidl-Hoffmann, C
Picard, C
Marodi, L
Morio, T
Kobayashi, M
Lilic, D
Milner, JD
Holland, S
Casanova, JL
Puel, A
AF Toubiana, Julie
Okada, Satoshi
Hiller, Julia
Oleastro, Matias
Lagos Gomez, Macarena
Aldave Becerra, Juan Carlos
Ouachee-Chardin, Marie
Fouyssac, Fanny
Girisha, Katta Mohan
Etzioni, Amos
Van Montfrans, Joris
Camcioglu, Yildiz
Kerns, Leigh Ann
Belohradsky, Bernd
Blanche, Stephane
Bousfiha, Aziz
Rodriguez-Gallego, Carlos
Meyts, Isabelle
Kisand, Kai
Reichenbach, Janine
Renner, Ellen D.
Rosenzweig, Sergio
Grimbacher, Bodo
van de Veerdonk, Frank L.
Traidl-Hoffmann, Claudia
Picard, Capucine
Marodi, Laszlo
Morio, Tomohiro
Kobayashi, Masao
Lilic, Desa
Milner, Joshua D.
Holland, Steven
Casanova, Jean-Laurent
Puel, Anne
CA STAT1 Gain Function Study Grp
TI Heterozygous STAT1 gain-of-function mutations underlie an unexpectedly
broad clinical phenotype
SO BLOOD
LA English
DT Article
ID CHRONIC MUCOCUTANEOUS CANDIDIASIS; HYPER-IGE SYNDROME; PROGRESSIVE
MULTIFOCAL LEUKOENCEPHALOPATHY; AICARDI-GOUTIERES-SYNDROME; FUNCTION
SIGNAL TRANSDUCER; HOMOZYGOUS CARD9 MUTATION; AUTOSOMAL-DOMINANT GAIN;
CYTOKINE GM-CSF; SYNDROME TYPE-I; INBORN-ERRORS
AB Since their discovery in patients with autosomal dominant (AD) chronic mucocutaneous candidiasis (CMC) in 2011, heterozygous STAT1 gain-of-function (GOF) mutations have increasingly been identified worldwide. The clinical spectrum associated with them needed to be delineated. We enrolled 274 patients from 167 kindreds originating from 40 countries from 5 continents. Demographic data, clinical features, immunological parameters, treatment, and outcome were recorded. The median age of the 274 patients was 22 years (range, 1-71 years); 98% of them had CMC, with a median age at onset of 1 year (range, 0-24 years). Patients often displayed bacterial (74%) infections, mostly because of Staphylococcus aureus (36%), including the respiratory tract and the skin in 47% and 28% of patients, respectively, and viral (38%) infections, mostly because of Herpesviridae (83%) and affecting the skin in 32% of patients. Invasive fungal infections (10%), mostly caused by Candida spp. (29%), and mycobacterial disease (6%) caused by Mycobacterium tuberculosis, environmental mycobacteria, or Bacille Calmette-Guerin vaccines were less common. Many patients had autoimmune manifestations (37%), including hypothyroidism(22%), type 1 diabetes (4%), blood cytopenia (4%), and systemic lupus erythematosus (2%). Invasive infections (25%), cerebral aneurysms(6%), and cancers (6%) were the strongest predictors of poor outcome. CMC persisted in 39% of the 202 patients receiving prolonged antifungal treatment. Circulating interleukin-17A-producing T-cell count was low for most (82%) but not all of the patients tested. STAT1 GOF mutations underlie AD CMC, as well as an unexpectedly wide range of other clinical features, including not only a variety of infectious and autoimmune diseases, but also cerebral aneurysms and carcinomas that confer a poor prognosis.
C1 [Toubiana, Julie] Necker Enfants Malades Hosp, AP HP, Dept Gen Pediat & Pediat Infect Dis, Paris, France.
[Toubiana, Julie; Blanche, Stephane; Casanova, Jean-Laurent; Puel, Anne] Paris Descartes Univ, Sorbonne Paris Cite, Inst Imagine, Paris, France.
[Toubiana, Julie; Picard, Capucine; Casanova, Jean-Laurent; Puel, Anne] Necker Med Sch, Lab Human Genet Infect Dis, Necker Branch, INSERM,UMR1163, Paris, France.
[Toubiana, Julie; Blanche, Stephane; Picard, Capucine] Necker Enfants Malades Hosp, AP HP, Pediat Hematol Immunol Rheumatol Unit, Paris, France.
[Okada, Satoshi; Casanova, Jean-Laurent; Puel, Anne] Rockefeller Univ, Rockefeller Branch, St Giles Lab Human Genet Infect Dis, 1230 York Ave, New York, NY 10021 USA.
[Okada, Satoshi; Kobayashi, Masao] Hiroshima Univ, Grad Sch Biomed & Hlth Sci, Dept Pediat, Hiroshima, Japan.
[Hiller, Julia; Traidl-Hoffmann, Claudia] Tech Univ, UNIKA T, Inst Environm Med, Augsburg, Germany.
[Hiller, Julia; Traidl-Hoffmann, Claudia] Helmholtz Ctr Munich, Augsburg, Germany.
[Hiller, Julia; Traidl-Hoffmann, Claudia] CK CARE, Davos, Switzerland.
[Oleastro, Matias] Juan Pedro Garrahan Natl Hosp Pediat, Immunol & Reumatholoy Dept, Buenos Aires, DF, Argentina.
[Lagos Gomez, Macarena] Univ Valparaiso, Sch Med, Dept Preclin, Valparaiso, Chile.
[Lagos Gomez, Macarena] Padre Hurtado Clin Alemana Santiago Hosp, Valparaiso, Chile.
[Aldave Becerra, Juan Carlos] Edgardo Rebagliati Martins Natl Hosp, Allergy & Immunol Div, Lima, Peru.
[Ouachee-Chardin, Marie] Robert Debre Hosp, AP HP, Pediat Hematol Oncol Unit, Paris, France.
[Fouyssac, Fanny] Children Hosp, Pediat Oncol & Hematol Unit, Vandoeuvre Les Nancy, France.
[Girisha, Katta Mohan] Manipal Univ, Kasturba Med Coll, Dept Med Genet, Manipal, India.
[Etzioni, Amos] Meyer Childrens Hosp, Haifa, Israel.
[Van Montfrans, Joris] Univ Utrecht, Med Ctr, Dept Pediat Immunol Hematol & Infect Dis, Utrecht, Netherlands.
[Camcioglu, Yildiz] Istanbul Univ, Cerrahpasa Med Sch, Infect Dis Clin Immunol & Allergy Div, Dept Pediat, Istanbul, Turkey.
[Kerns, Leigh Ann] Rainbow Babies & Childrens Hosp, Case Med Ctr, Div Pediat Pulmonol Allergy Immunol & Sleep Med, 2101 Adelbert Rd, Cleveland, OH 44106 USA.
[Belohradsky, Bernd; Renner, Ellen D.] Univ Munich, Dr von Hauner Childrens Hosp, Munich, Germany.
[Bousfiha, Aziz] King Hassan II Univ, Ibn Rochd Hosp, Dept Pediat Infect Dis, Clin Immunol Unit, Casablanca, Morocco.
[Rodriguez-Gallego, Carlos] Son Espases Univ Hosp, Dept Immunol, Palma de Mallorca, Spain.
[Meyts, Isabelle] Leuven Univ Hosp, Dept Pediat, Leuven, Belgium.
[Kisand, Kai] Univ Tartu, Inst Biomed & Translat Med, Ulikooli 18, EE-50090 Tartu, Estonia.
[Reichenbach, Janine] Univ Zurich, Univ Childrens Hosp, Div Immunol, Zurich, Switzerland.
[Reichenbach, Janine] Univ Zurich, Childrens Res Ctr, Zurich, Switzerland.
[Rosenzweig, Sergio; Holland, Steven] NIAID, Lab Clin Infect Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Grimbacher, Bodo] Univ Freiburg, Med Ctr, Ctr Chron Immunodeficiency, Hugstetter Str 55, D-79106 Freiburg, Germany.
[Grimbacher, Bodo] Univ Freiburg, Hugstetter Str 55, D-79106 Freiburg, Germany.
[van de Veerdonk, Frank L.] Radboud Univ Nijmegen, Med Ctr, Radboud Ctr Infect Dis, Dept Internal Med, NL-6525 ED Nijmegen, Netherlands.
[Picard, Capucine] Necker Enfants Malades Hosp, AP HP, Study Ctr Immunodeficiencies, Paris, France.
[Marodi, Laszlo] Univ Debrecen, Fac Med, Dept Infect Dis & Pediat Immunol, Debrecen, Hungary.
[Morio, Tomohiro] Tokyo Med & Dent Univ, Dept Pediat & Dev Biol, Tokyo, Japan.
[Lilic, Desa] Newcastle Univ, Inst Cellular Med, Primary Immunodeficiency Grp, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England.
[Milner, Joshua D.] NIAID, Lab Allerg Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Casanova, Jean-Laurent] Howard Hughes Med Inst, New York, NY USA.
[Puel, Anne] Necker Enfants Malades Hosp, AP HP, Dept Infect & Trop Dis, Paris, France.
RP Puel, A (reprint author), Necker Enfants Malades Hosp, AP HP, Dept Infect & Trop Dis, Paris, France.; Puel, A (reprint author), Necker Enfants Malades Hosp, Lab Human Genet Infect Dis, Necker Branch, INSERM,UMR1163,Imagine Inst, 24 Blvd Montparnasse, F-75015 Paris, France.
EM anne.puel@inserm.fr
RI Okada, Satoshi/B-8901-2011; Kisand, Kai/J-3483-2015;
OI Okada, Satoshi/0000-0002-4622-5657; Kisand, Kai/0000-0002-5426-4648;
Traidl-Hoffmann, Claudia/0000-0001-5085-5179
FU French National Research Agency (ANR) under the "Investments for the
future" program [ANR-10-IAHU-01]; French National Research Agency (ANR)
under GENCMCD grant [ANR-11-BSV3-005-01]; French National Research
Agency (ANR) under HGDIFD [ANR-14-CE15-0006]; French National Research
Agency (ANR) under Laboratoire d'Excellence Integrative Biology of
Emerging Infectious Diseases [ANR-10-LABX-62-IBEID]; INSERM; University
Paris Descartes; Jeffrey Modell Foundation-Translational Research
Program; Jeffrey Modell Centers Network; Rockefeller University; St.
Giles Foundation; National Institute of Allergy and Infectious Diseases,
National Institutes of Health [U01AI109697]; ERA-Net for Research
Programmes on Rare Diseases "E-RARE EURO CMC" [ANR-14-RARE-0005-02];
Helmholtz Center grant DZIF [8000805-3_TTU_IICH 07.801]; Gebert Ruf
Stiftung-programme Rare Diseases-New Approaches, EUFP7 CELL-PID, EUFP7
NET4CGD, ZIHP; Ministerio de Sanidad, Spain from the Regional
Development Fund-European Social Fund (FEDER-FSE) [PI13/1456]
FX The Laboratory of Human Genetics of Infectious Diseases was supported by
the French National Research Agency (ANR) under the "Investments for the
future" program (ANR-10-IAHU-01), GENCMCD grant (ANR-11-BSV3-005-01),
HGDIFD (ANR-14-CE15-0006), and Laboratoire d'Excellence Integrative
Biology of Emerging Infectious Diseases (#ANR-10-LABX-62-IBEID); INSERM;
University Paris Descartes; the Jeffrey Modell Foundation-Translational
Research Program; the Jeffrey Modell Centers Network; the Rockefeller
University; the St. Giles Foundation; and the National Institute of
Allergy and Infectious Diseases, National Institutes of Health (grant
U01AI109697). This work was also supported by the ERA-Net for Research
Programmes on Rare Diseases "E-RARE EURO CMC" (ANR-14-RARE-0005-02).
B.G. was supported by the Helmholtz Center grant DZIF
(8000805-3_TTU_IICH 07.801). J.R. was supported by Gebert Ruf
Stiftung-programme Rare Diseases-New Approaches, EUFP7 CELL-PID, EUFP7
NET4CGD, ZIHP. C.R.-G. was supported by the Ministerio de Sanidad, Spain
(grant PI13/1456), from the Regional Development Fund-European Social
Fund (FEDER-FSE).
NR 88
TC 13
Z9 13
U1 3
U2 6
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA
SN 0006-4971
EI 1528-0020
J9 BLOOD
JI Blood
PD JUN 23
PY 2016
VL 127
IS 25
BP 3154
EP 3164
DI 10.1182/blood-2015-11-679902
PG 11
WC Hematology
SC Hematology
GA DP2RK
UT WOS:000378337700009
PM 27114460
ER
PT J
AU Le Gall, SM
Szabo, R
Lee, M
Kirchhofer, D
Craik, CS
Bugge, TH
Camerer, E
AF Le Gall, Sylvain M.
Szabo, Roman
Lee, Melody
Kirchhofer, Daniel
Craik, Charles S.
Bugge, Thomas H.
Camerer, Eric
TI Matriptase activation connects tissue factor-dependent coagulation
initiation to epithelial proteolysis and signaling
SO BLOOD
LA English
DT Article
ID SERINE-PROTEASE MATRIPTASE; HEPATOCYTE GROWTH-FACTOR; EPIDERMAL BARRIER
FUNCTION; FACTOR CYTOPLASMIC DOMAIN; NEURAL-TUBE CLOSURE; CANINE
KIDNEY-CELLS; ENDOTHELIAL-CELLS; FACTOR VIIA; RECEPTOR 2;
BLOOD-COAGULATION
AB The coagulation cascade is designed to sense tissue injury by physical separation of the membrane-anchored cofactor tissue factor (TF) from inactive precursors of coagulation proteases circulating in plasma. Once TF on epithelial and other extravascular cells is exposed to plasma, sequential activation of coagulation proteases coordinates hemostasis and contributes to host defense and tissue repair. Membrane-anchored serine proteases (MASPs) play critical roles in the development and homeostasis of epithelial barrier tissues; how MASPs are activated in mature epithelia is unknown. We here report that proteases of the extrinsic pathway of blood coagulation transactivate the MASP matriptase, thus connecting coagulation initiation to epithelial proteolysis and signaling. Exposure of TF-expressing cells to factors (F) VIIa and Xa triggered the conversion of latent pro-matriptase to an active protease, which in turn cleaved the pericellular substrates protease-activated receptor-2 (PAR2) and pro-urokinase. An activation pathway-selective PAR2 mutant resistant to direct cleavage by TF: FVIIa and FXa was activated by these proteases when cells co-expressed pro-matriptase, and matriptase transactivation was necessary for efficient cleavage and activation of wild-type PAR2 by physiological concentrations of TF: FVIIa and FXa. The coagulation initiation complex induced rapid and prolonged enhancement of the barrier function of epithelial monolayers that was dependent on matriptase transactivation andPAR2signaling. These observations suggest that the coagulation cascade engages matriptase to help coordinate epithelial defense and repair programs after injury or infection, and that matriptase may contribute to TF-driven pathogenesis in cancer and inflammation.
C1 [Le Gall, Sylvain M.; Camerer, Eric] Paris Cardiovasc Res Ctr, INSERM, U970, 56 Rue Leblanc, F-75015 Paris, France.
[Le Gall, Sylvain M.; Camerer, Eric] Univ Paris 05, Paris, France.
[Szabo, Roman; Bugge, Thomas H.] Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD USA.
[Lee, Melody; Craik, Charles S.] Univ Calif San Francisco, Dept Pharmaceut Chem, San Francisco, CA USA.
[Kirchhofer, Daniel] Genentech Inc, Dept Early Discovery Biochem, San Francisco, CA 94080 USA.
RP Camerer, E (reprint author), Paris Cardiovasc Res Ctr, INSERM, U970, 56 Rue Leblanc, F-75015 Paris, France.
EM eric.camerer@inserm.fr
FU INSERM Avenir; Marie Curie Actions [IRG-249193]; French National
Research Agency [ANR-10-MIDI-0003, ANR-15-CE14-0009]; Ile-de-France
Region; US Department of Defense [PC 11318]; National Institute of
Dental and Craniofacial Research Intramural Research Program
FX This work was funded by INSERM Avenir, Marie Curie Actions (IRG-249193),
the French National Research Agency (ANR-10-MIDI-0003,
ANR-15-CE14-0009), the Ile-de-France Region (E.C.), the US Department of
Defense PC 11318 (C.S.C.) and by the National Institute of Dental and
Craniofacial Research Intramural Research Program (T.H.B.).
NR 81
TC 2
Z9 2
U1 4
U2 4
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA
SN 0006-4971
EI 1528-0020
J9 BLOOD
JI Blood
PD JUN 23
PY 2016
VL 127
IS 25
BP 3260
EP 3269
DI 10.1182/blood-2015-11-683110
PG 10
WC Hematology
SC Hematology
GA DP2RK
UT WOS:000378337700019
PM 27114461
ER
PT J
AU Zhao, WD
Hamid, E
Shin, W
Wen, PJ
Krystofiak, ES
Villarreal, SA
Chiang, HC
Kachar, B
Wu, LG
AF Zhao, Wei-Dong
Hamid, Edaeni
Shin, Wonchul
Wen, Peter J.
Krystofiak, Evan S.
Villarreal, Seth A.
Chiang, Hsueh-Cheng
Kachar, Bechara
Wu, Ling-Gang
TI Hemi-fused structure mediates and controls fusion and fission in live
cells
SO NATURE
LA English
DT Article
ID MEMBRANE FISSION; CHROMAFFIN CELLS; CA2+-TRIGGERED EXOCYTOSIS; SNARE
COMPLEX; PORES; VESICLES; ENDOCYTOSIS; TOMOGRAPHY; PROTEINS;
INTERMEDIATE
AB Membrane fusion and fission are vital for eukaryotic life(1-5). For three decades, it has been proposed that fusion is mediated by fusion between the proximal leaflets of two bilayers (hemi-fusion) to produce a hemi-fused structure, followed by fusion between the distal leaflets, whereas fission is via hemi-fission, which also produces a hemi-fused structure, followed by full fission(1,4,6-10). This hypothesis remained unsupported owing to the lack of observation of hemi-fusion or hemi-fission in live cells. A competing fusion hypothesis involving protein-lined pore formation has also been proposed(2,11-15). Here we report the observation of a hemi-fused Omega-shaped structure in live neuroendocrine chromaffin cells and pancreatic beta-cells, visualized using confocal and super-resolution stimulated emission depletion microscopy. This structure is generated from fusion pore opening or closure (fission) at the plasma membrane. Unexpectedly, the transition to full fusion or fission is determined by competition between fusion and calcium/dynamin-dependent fission mechanisms, and is notably slow (seconds to tens of seconds) in a substantial fraction of the events. These results provide key missing evidence in support of the hemi-fusion and hemi-fission hypothesis in live cells, and reveal the hemi-fused intermediate as a key structure controlling fusion and fission, as fusion and fission mechanisms compete to determine the transition to fusion or fission.
C1 [Zhao, Wei-Dong; Hamid, Edaeni; Shin, Wonchul; Wen, Peter J.; Villarreal, Seth A.; Chiang, Hsueh-Cheng; Wu, Ling-Gang] NINDS, 35 Convent Dr,Room 2B-1012, Bethesda, MD 20892 USA.
[Krystofiak, Evan S.; Kachar, Bechara] NIDCD, 35A Convent Dr,Room 3D-824, Bethesda, MD 20892 USA.
[Chiang, Hsueh-Cheng] Natl Cheng Kung Univ, Dept Pharmacol, Coll Med, 1 Univ Rd, Tainan 701, Taiwan.
RP Wu, LG (reprint author), NINDS, 35 Convent Dr,Room 2B-1012, Bethesda, MD 20892 USA.
EM wul@ninds.nih.gov
FU National Institute of Neurological Disorders and Stroke Intramural
Research Program [ZIA NS003009-13, ZIA NS003105-08]; National Institute
on Deafness and Other Communication Disorders (NIDCD) Intramural
Research Program [Z01-DC000002]; National Institute on Deafness and
Other Communication Disorders (NIDCD) Intramural Research Program (NIDCD
Advanced Imaging Core ZIC) [DC000081]
FX We thank T. Balla, G. Miesenbock, and D.-S. Wang for providing the
construct containing the GFP-fused PH domain of PLC delta 1, the
VAMP2-pHluorin construct, and dynamin siRNA, respectively; C. Smith for
technical support with STED microscopy; and S. Cheng and V. Crocker for
their electron microscopy technical support. This work was supported by
the National Institute of Neurological Disorders and Stroke Intramural
Research Program (ZIA NS003009-13 and ZIA NS003105-08) and National
Institute on Deafness and Other Communication Disorders (NIDCD)
Intramural Research Program (Z01-DC000002 and NIDCD Advanced Imaging
Core ZIC DC000081).
NR 34
TC 9
Z9 9
U1 13
U2 22
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 23
PY 2016
VL 534
IS 7608
BP 548
EP +
DI 10.1038/nature18598
PG 21
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DP1SS
UT WOS:000378270300053
PM 27309816
ER
PT J
AU Gottschalk, RA
Martins, AJ
Angermann, BR
Dutta, B
Ng, CE
Uderhardt, S
Tsang, JS
Fraser, IDC
Meier-Schellersheim, M
Germain, RN
AF Gottschalk, Rachel A.
Martins, Andrew J.
Angermann, Bastian R.
Dutta, Bhaskar
Ng, Caleb E.
Uderhardt, Stefan
Tsang, John S.
Fraser, Iain D. C.
Meier-Schellersheim, Martin
Germain, Ronald N.
TI Distinct NF-kappa B and MAPK Activation Thresholds Uncouple Steady-
State Microbe Sensing from Anti-pathogen Inflammatory Responses
SO CELL SYSTEMS
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; BOWEL-DISEASE; SUSCEPTIBILITY LOCI;
COLORECTAL-CANCER; IMMUNE ACTIVATION; INNATE IMMUNITY; TNF; RECOGNITION;
PATHWAYS; LIPOPOLYSACCHARIDE
AB The innate immune system distinguishes low-level homeostatic microbial stimuli from those of invasive pathogens, yet we lack understanding of how qualitatively similar microbial products yield context-specific macrophage functional responses. Using quantitative approaches, we found that NF-kappa B and MAPK signaling was activated at different concentrations of a stimulatory TLR4 ligand in both mouse and human macrophages. Above a threshold of ligand, MAPK were activated in a switch-like manner, facilitating production of inflammatory mediators. At ligand concentrations below this threshold, NF-kappa B signaling occurred, promoting expression of a restricted set of genes and macrophage priming. Among TLR-induced genes, we observed an inverse correlation between MAPK dependence and ligand sensitivity, highlighting the role of this signaling dichotomy in partitioning innate responses downstream of a single receptor. Our study reveals an evolutionarily conserved innate immune response system in which danger discrimination is enforced by distinct thresholds for NF-kappa B and MAPK activation, which provide sequential barriers to inflammatory mediator production.
C1 [Gottschalk, Rachel A.; Dutta, Bhaskar; Ng, Caleb E.; Uderhardt, Stefan; Germain, Ronald N.] NIAID, Lymphocyte Biol Sect, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Martins, Andrew J.; Tsang, John S.] NIAID, Syst Genom & Bioinformat Unit, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Angermann, Bastian R.; Meier-Schellersheim, Martin] NIAID, Computat Biol Sect, Lab Syst Biol, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Ng, Caleb E.] Univ Penn, Immunol Grad Grp, Philadelphia, PA 19104 USA.
[Fraser, Iain D. C.] NIAID, Signaling Syst Unit, Lab Syst Biol, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Dutta, Bhaskar] AstraZeneca, Adv Analyt Ctr, Gaithersburg, MD 20878 USA.
RP Gottschalk, RA; Germain, RN (reprint author), NIAID, Lymphocyte Biol Sect, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM gottschalkra@niaid.nih.gov; rgermain@niaid.nih.gov
FU Intramural Research Program of National Institute of Allergy and
Infectious Diseases, NIH
FX We thank M. Narayanan, A. Nita-Lazar, V. Sjoelund, S.J. Vayttaden, and
members of the R.N.G. laboratory and the Laboratory of Systems Biology
for helpful discussions. This work was supported by the Intramural
Research Program of National Institute of Allergy and Infectious
Diseases, NIH.
NR 52
TC 2
Z9 2
U1 1
U2 1
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 2405-4712
EI 2405-4720
J9 CELL SYST
JI Cell Syst.
PD JUN 22
PY 2016
VL 2
IS 6
BP 378
EP 390
DI 10.1016/j.cels.2016.04.016
PG 13
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA EL1DN
UT WOS:000394360800006
PM 27237739
ER
PT J
AU Pettit, SD
Lipshultz, SE
Cleeland, CS
Roberts, S
Davis, M
Berridge, BR
Kirch, RA
AF Pettit, Syril D.
Lipshultz, Steven E.
Cleeland, Charles S.
Roberts, Samantha
Davis, Myrtle
Berridge, Brian R.
Kirch, Rebecca A.
TI Enhancing quality of life as a goal for anticancer therapeutics
SO SCIENCE TRANSLATIONAL MEDICINE
LA English
DT Editorial Material
ID CLINICAL ONCOLOGY; AMERICAN SOCIETY; CANCER
C1 [Pettit, Syril D.] HESI, ILSI, Washington, DC 20005 USA.
[Lipshultz, Steven E.] Childrens Hosp Michigan, Detroit, MI 48201 USA.
[Lipshultz, Steven E.] Wayne State Univ, Sch Med, Pediat, Detroit, MI 48202 USA.
[Lipshultz, Steven E.] Univ Pediatricians, Detroit, MI USA.
[Lipshultz, Steven E.] Childrens Res Ctr Michigan, Detroit, MI 48201 USA.
[Cleeland, Charles S.] Univ Texas MD Anderson Canc Ctr, Canc Res, Dept Symptom Res, Div Internal Med, Houston, TX 77030 USA.
[Roberts, Samantha] Friends Canc Res, Sci Affairs, Washington, DC 20036 USA.
[Davis, Myrtle] US NCI, Toxicol & Pharmacol Branch, Dev Therapeut Program, Div Canc Treatment & Diag, Bethesda, MD 20892 USA.
[Berridge, Brian R.] GlaxoSmithKline, Worldwide Anim Res Strategy, King Of Prussia, PA 19406 USA.
[Kirch, Rebecca A.] Natl Patient Advocate Fdn, Healthcare Qual & Value, Washington, DC 20005 USA.
RP Pettit, SD (reprint author), HESI, ILSI, Washington, DC 20005 USA.
EM spettit@hesiglobal.org
FU NCI NIH HHS [P30 CA016672]
NR 7
TC 1
Z9 1
U1 0
U2 0
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 1946-6234
EI 1946-6242
J9 SCI TRANSL MED
JI Sci. Transl. Med.
PD JUN 22
PY 2016
VL 8
IS 344
AR 344ed9
DI 10.1126/scitranslmed.aag0382
PG 2
WC Cell Biology; Medicine, Research & Experimental
SC Cell Biology; Research & Experimental Medicine
GA DP8HJ
UT WOS:000378738500001
PM 27334258
ER
PT J
AU Warren, BL
Mendoza, MP
Cruz, FC
Leao, RM
Caprioli, D
Rubio, FJ
Whitaker, LR
McPherson, KB
Bossert, JM
Shaham, Y
Hope, BT
AF Warren, Brandon L.
Mendoza, Michael P.
Cruz, Fabio C.
Leao, Rodrigo M.
Caprioli, Daniele
Rubio, F. Javier
Whitaker, Leslie R.
McPherson, Kylie B.
Bossert, Jennifer M.
Shaham, Yavin
Hope, Bruce T.
TI Distinct Fos-Expressing Neuronal Ensembles in the Ventromedial
Prefrontal Cortex Mediate Food Reward and Extinction Memories
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
DE Daun02 inactivation; food reward; operant conditioning; RNAscope; vmPFC
ID COCAINE-SEEKING BEHAVIOR; CONTEXT-INDUCED REINSTATEMENT; STRESS-INDUCED
REINSTATEMENT; INFRALIMBIC CORTEX; NUCLEUS-ACCUMBENS; METHAMPHETAMINE
SEEKING; OPTOGENETIC INHIBITION; ALCOHOL-SEEKING; FEMALE RATS;
INCUBATION
AB In operant learning, initial reward-associated memories are thought to be distinct from subsequent extinction-associated memories. Memories formed during operant learning are thought to be stored in "neuronal ensembles." Thus, we hypothesize that different neuronal ensembles encode reward-and extinction-associated memories. Here, we examined prefrontal cortex neuronal ensembles involved in the recall of reward and extinction memories of food self-administration. We first trained rats to lever press for palatable food pellets for 7 d (1 h/d) and then exposed them to 0, 2, or 7 daily extinction sessions in which lever presses were not reinforced. Twenty-four hours after the last training or extinction session, we exposed the rats to either a short 15 min extinction test session or left them in their homecage (a control condition). We found maximal Fos (a neuronal activity marker) immunoreactivity in the ventral medial prefrontal cortex of rats that previously received 2 extinction sessions, suggesting that neuronal ensembles in this area encode extinction memories. We then used the Daun02 inactivation procedure to selectively disrupt ventral medial prefrontal cortex neuronal ensembles that were activated during the 15 min extinction session following 0 (no extinction) or 2 prior extinction sessions to determine the effects of inactivating the putative food reward and extinction ensembles, respectively, on subsequent nonreinforced food seeking 2 d later. Inactivation of the food reward ensembles decreased food seeking, whereas inactivation of the extinction ensembles increased food seeking. Our results indicate that distinct neuronal ensembles encoding operant reward and extinction memories intermingle within the same cortical area.
C1 [Warren, Brandon L.; Mendoza, Michael P.; Cruz, Fabio C.; Leao, Rodrigo M.; Caprioli, Daniele; Rubio, F. Javier; Whitaker, Leslie R.; McPherson, Kylie B.; Bossert, Jennifer M.; Shaham, Yavin; Hope, Bruce T.] NIDA, Behav Neurosci Branch, Intramural Res Program, NIH,Dept Hlth & Human Serv, 251 Bayview Blvd,Suite 200, Baltimore, MD 21224 USA.
RP Hope, BT (reprint author), NIDA, Behav Neurosci Branch, Intramural Res Program, NIH,Dept Hlth & Human Serv, 251 Bayview Blvd,Suite 200, Baltimore, MD 21224 USA.
EM bhope@intra.nida.nih.gov
RI Hope, Bruce/A-9223-2010;
OI Hope, Bruce/0000-0001-5804-7061; McPherson, Kylie/0000-0002-5196-098X
FU Intramural Research Program/National Institute on Drug Abuse/National
Institutes of Health
FX This work was supported by the Intramural Research Program/National
Institute on Drug Abuse/National Institutes of Health.
NR 57
TC 5
Z9 5
U1 2
U2 8
PU SOC NEUROSCIENCE
PI WASHINGTON
PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA
SN 0270-6474
J9 J NEUROSCI
JI J. Neurosci.
PD JUN 22
PY 2016
VL 36
IS 25
BP 6691
EP 6703
DI 10.1523/JNEUROSCI.0140-16.2016
PG 13
WC Neurosciences
SC Neurosciences & Neurology
GA DQ2FQ
UT WOS:000379018100009
PM 27335401
ER
PT J
AU Tada, N
Jansen, DJ
Mower, MP
Blewett, MM
Umotoy, JC
Cravatt, BF
Wolan, DW
Shenvi, RA
AF Tada, Norihiro
Jansen, Daniel J.
Mower, Matthew P.
Blewett, Megan M.
Umotoy, Jeffrey C.
Cravatt, Benjamin F.
Wolan, Dennis W.
Shenvi, Ryan A.
TI Synthesis and Sulfur Electrophilicity of the Nuphar Thiaspirane
Pharmacophore
SO ACS CENTRAL SCIENCE
LA English
DT Article
ID DIMERIC SESQUITERPENE THIOALKALOIDS; STRUCTURAL REQUIREMENTS;
HYDROGEN-SULFIDE; ALKALOIDS; LUTEUM; NEOTHIOBINUPHARIDINE; APOPTOSIS;
PUMILUM; THIOBINUPHARIDINE; SULFOXIDES
AB We describe a general method to synthesize the iminium tetrahydrothiophene embedded in the dimeric Nuphar alkaloids. In contrast to prior studies, the sulfur atom of the thiaspirane pharmacophore is shown to be electrophilic. This a-thioether reacts with thiophenol or glutathione at ambient temperature to cleave the C-S bond and form a disulfide. Rates of conversion are proportional to the corresponding ammonium ion pK(a) and exhibit half-lives less than 5 h at a 5 mM concentration of thiol. A simple thiophane analogue of the Nuphar dimers causes apoptosis at single-digit micromolar concentration and labels reactive cysteines at similar levels as the unsaturated iminium "warhead". Our experiments combined with prior observations suggest the sulfur of the Nuphar dimers can react as an electrophile in cellular environments and that sulfur-triggered retrodimerization can occur in the cell.
C1 [Tada, Norihiro; Jansen, Daniel J.; Mower, Matthew P.; Blewett, Megan M.; Umotoy, Jeffrey C.; Cravatt, Benjamin F.; Wolan, Dennis W.; Shenvi, Ryan A.] Scripps Res Inst, Dept Chem, 10550 North Torrey Pines Rd, La Jolla, CA 92037 USA.
[Jansen, Daniel J.] NIH, Natl Ctr Adv Translat Sci, 9800 Med Ctr Dr, Rockville, MD 20850 USA.
RP Shenvi, RA (reprint author), Scripps Res Inst, Dept Chem, 10550 North Torrey Pines Rd, La Jolla, CA 92037 USA.
EM rshenvi@scripps.edu
OI Shenvi, Ryan/0000-0001-8353-6449; Wolan, Dennis/0000-0001-9879-8353
FU NIGMS NIH HHS [R01 GM105766]
NR 64
TC 2
Z9 2
U1 7
U2 9
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 2374-7943
EI 2374-7951
J9 ACS CENTRAL SCI
JI ACS Central Sci.
PD JUN 22
PY 2016
VL 2
IS 6
BP 401
EP 408
DI 10.1021/acscentsci.6b00113
PG 8
WC Chemistry, Multidisciplinary
SC Chemistry
GA DP7OZ
UT WOS:000378690000009
PM 27413784
ER
PT J
AU Wheeler, AR
Fulton, KA
Gaudette, JE
Simmons, RA
Matsuo, I
Simmons, JA
AF Wheeler, Alyssa R.
Fulton, Kara A.
Gaudette, Jason E.
Simmons, Ryan A.
Matsuo, Ikuo
Simmons, James A.
TI Echolocating Big Brown Bats, Eptesicus fuscus, Modulate Pulse Intervals
to Overcome Range Ambiguity in Cluttered Surroundings
SO FRONTIERS IN BEHAVIORAL NEUROSCIENCE
LA English
DT Article
DE echolocation; sonar; clutter; bat; range ambiguity
ID ADAPTIVE ECHOLOCATION; AUDITORY SCENE; SONAR IMAGES; BEHAVIOR; BIOSONAR;
SIGNALS; TARGET; AVOIDANCE; DESIGN; CALLS
AB Big brown bats (Eptesicus fuscus) emit trains of brief, wideband frequency-modulated (FM) echolocation sounds and use echoes of these sounds to orient, find insects, and guide flight through vegetation. They are observed to emit sounds that alternate between short and long inter-pulse intervals (IPIs), forming sonar sound groups. The occurrence of these strobe groups has been linked to flight in cluttered acoustic environments, but how exactly bats use sonar sound groups to orient and navigate is still a mystery. Here, the production of sound groups during clutter navigation was examined. Controlled flight experiments were conducted where the proximity of the nearest obstacles was systematically decreased while the extended scene was kept constant. Four bats flew along a corridor of varying widths (100, 70, and 40 cm) bounded by rows of vertically hanging plastic chains while in-flight echolocation calls were recorded. Bats shortened their IPIs for more rapid spatial sampling and also grouped their sounds more tightly when flying in narrower corridors. Bats emitted echolocation calls with progressively shorter IPIs over the course of a flight, and began their flights by emitting shorter starting IPI calls when clutter was denser. The percentage of sound groups containing 3 or more calls increased with increasing clutter proximity. Moreover, IPI sequences having internal structure become more pronounced when corridor width narrows. A novel metric for analyzing the temporal organization of sound sequences was developed, and the results indicate that the time interval between echolocation calls depends heavily on the preceding time interval. The occurrence of specific IPI patterns were dependent upon clutter, which suggests that sonar sound grouping may be an adaptive strategy for coping with pulse-echo ambiguity in cluttered surroundings.
C1 [Wheeler, Alyssa R.; Fulton, Kara A.; Gaudette, Jason E.; Simmons, James A.] Brown Univ, Dept Neurosci, Providence, RI 02912 USA.
[Fulton, Kara A.] NINDS, Circuit Dynam & Connect Unit, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
[Gaudette, Jason E.] US Navy, Undersea Warfare Ctr, Sensors & Sonar Syst Dept, Newport, RI USA.
[Simmons, Ryan A.] Duke Univ, Sch Med, Dept Biostat & Bioinformat, Durham, NC USA.
[Matsuo, Ikuo] Tohoku Gakuin Univ, Dept Informat Sci, Sendai, Miyagi 980, Japan.
RP Wheeler, AR (reprint author), Brown Univ, Dept Neurosci, Providence, RI 02912 USA.
EM alyssa_wheeler@alumni.brown.edu
FU ONR Grant [N00014-14-1-05880]
FX The authors thank Aidan Leonard and Uday Shriram for work in the control
room, Laura Kloepper for help in the flight room, and Andrea Simmons for
suggestions that improved the manuscript. This work was supported by ONR
Grant N00014-14-1-05880 to JS and internal investments by NUWC Division
Newport to JG.
NR 43
TC 1
Z9 1
U1 8
U2 18
PU FRONTIERS MEDIA SA
PI LAUSANNE
PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015,
SWITZERLAND
SN 1662-5153
J9 FRONT BEHAV NEUROSCI
JI Front. Behav. Neurosci.
PD JUN 22
PY 2016
VL 10
AR 125
DI 10.3389/fnbeh.2016.00125
PG 13
WC Behavioral Sciences; Neurosciences
SC Behavioral Sciences; Neurosciences & Neurology
GA DP4ZA
UT WOS:000378504600001
PM 27445723
ER
PT J
AU Gichohi-Wainaina, WN
Tanaka, T
Towers, GW
Verhoef, H
Veenemans, J
Talsma, EF
Harryvan, J
Boekschoten, MV
Feskens, EJ
Melse-Boonstra, A
AF Gichohi-Wainaina, Wanjiku N.
Tanaka, Toshiko
Towers, G. Wayne
Verhoef, Hans
Veenemans, Jacobien
Talsma, Elise F.
Harryvan, Jan
Boekschoten, Mark V.
Feskens, Edith J.
Melse-Boonstra, Alida
TI Associations between Common Variants in Iron-Related Genes with
Haematological Traits in Populations of African Ancestry
SO PLOS ONE
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; BLOOD-CELL TRAITS; DEFICIENCY ANEMIA; SERUM
IRON; TRANSFERRIN SATURATION; HEMOGLOBIN LEVELS; TMPRSS6; AMERICANS;
CHILDREN; FERRITIN
AB Background
Large genome-wide association (GWA) studies of European ancestry individuals have identified multiple genetic variants influencing iron status. Studies on the generalizability of these associations to African ancestry populations have been limited. These studies are important given interethnic differences in iron status and the disproportionate burden of iron deficiency among African ancestry populations.
Methods
We tested the associations of 20 previously identified iron status-associated single nucleotide polymorphisms (SNPs) in 628 Kenyans, 609 Tanzanians, 608 South Africans and 228 African Americans. In each study, we examined the associations present between 20 SNPs with ferritin and haemoglobin, adjusting for age, sex and CRP levels.
Results
In the meta analysis including all 4 African ancestry cohorts, we replicated previously reported associations with lowered haemoglobin concentrations for rs2413450 (beta = -0.19, P = 0.02) and rs4820268 (beta = -0.16, P = 0.04) in TMPRSS6. An association with increased ferritin concentrations was also confirmed for rs1867504 in TF (beta = 1.04, P = <0.0001) in the meta analysis including the African cohorts only.
Conclusions
In all meta analyses, we only replicated 4 of the 20 single nucleotide polymorphisms reported to be associated with iron status in large GWA studies of European ancestry individuals. While there is now evidence for the associations of a number of genetic variants with iron status in both European and African ancestry populations, the considerable lack of concordance highlights the importance of continued ancestry-specific studies to elucidate the genetic underpinnings of iron status in ethnically diverse populations.
C1 [Gichohi-Wainaina, Wanjiku N.; Harryvan, Jan; Feskens, Edith J.; Melse-Boonstra, Alida] Wageningen Univ, Div Human Nutr, NL-6700 AP Wageningen, Netherlands.
[Gichohi-Wainaina, Wanjiku N.] IITA, Dar Es Salaam, Tanzania.
[Tanaka, Toshiko] NIA, Translat Gerontol Branch, Baltimore, MD 21224 USA.
[Towers, G. Wayne] North West Univ, Ctr Excellence Nutr, Potchefstroom Campus, Potchefstroom, South Africa.
[Verhoef, Hans] Wageningen Univ, Cell Biol & Immunol Grp, NL-6700 AP Wageningen, Netherlands.
[Verhoef, Hans] London Sch Hyg & Trop Med, MRC, Int Nutr Grp, London WC1, England.
[Verhoef, Hans] Med Res Council Banjul, Banjul, Gambia.
[Veenemans, Jacobien] Amphia Hosp, Lab Microbiol & Infect Control, Breda, Netherlands.
[Veenemans, Jacobien] Admiraal De Ruyter Hosp, Dept Med Microbiol & Immunol, Goes, Netherlands.
[Talsma, Elise F.] CIAT, HarvestPlus, Cali, Colombia.
[Boekschoten, Mark V.] Wageningen Univ, Div Human Nutr, Nutr Metab & Genom Grp, NL-6700 AP Wageningen, Netherlands.
RP Gichohi-Wainaina, WN (reprint author), Wageningen Univ, Div Human Nutr, NL-6700 AP Wageningen, Netherlands.; Gichohi-Wainaina, WN (reprint author), IITA, Dar Es Salaam, Tanzania.
EM wngichohi@gmail.com
FU European Union's Seventh Framework Programme [FP7] [211484]; Netherlands
Organisation for Scientific Research (NWO)/WOTRO [W93-413, WAO93-441,
WIZ93-465]; UNICEF; Cornelis Visser Foundation; Wageningen University
(Interdisciplinary Research and Education Fund); South African Medical
Research Council (Self-Initiated Research Grants), Cape Town, South
Africa; Unilever R&D, Vlaardingen, The Netherlands; European Union (EU)
[MC-IRSES-2008-230786]; Intramural Research Program of the NIH; National
Institute on Aging
FX The Kenyan cohort research was conducted within the framework of INSTAPA
Project, funded by the European Union's Seventh Framework Programme
[FP7/2007-2013] under grant agreement nr 211484. The Tanzanian cohort
research was supported through funding from the Netherlands Organisation
for Scientific Research (NWO)/WOTRO [W93-413, WAO93-441, as well as
WIZ93-465, UNICEF, Cornelis Visser Foundation and Wageningen University
(Interdisciplinary Research and Education Fund). The PURE study was
supported through grants provided by the South African Medical Research
Council (Self-Initiated Research Grants), Cape Town, South Africa, with
further support from a fellowship provided by Unilever R&D, Vlaardingen,
The Netherlands, and from the European Union (EU) funded staff exchange
European-South African Partnership in Nutrition Research program (grant
MC-IRSES-2008-230786). The BLSA was supported through funding by the
Intramural Research Program of the NIH, National Institute on Aging. The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 59
TC 0
Z9 0
U1 1
U2 3
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUN 22
PY 2016
VL 11
IS 6
AR e0157996
DI 10.1371/journal.pone.0157996
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DP0WX
UT WOS:000378212800065
PM 27332551
ER
PT J
AU Gorgolewski, KJ
Auer, T
Calhoun, VD
Craddock, RC
Das, S
Duff, EP
Flandin, G
Ghosh, SS
Glatard, T
Halchenko, YO
Handwerker, DA
Hanke, M
Keator, D
Li, XR
Michael, Z
Maumet, C
Nichols, BN
Nichols, TE
Pellman, J
Poline, JB
Rokem, A
Schaefer, G
Sochat, V
Triplett, W
Tumer, JA
Varoquaux, G
Poldrack, RA
AF Gorgolewski, Krzysztof J.
Auer, Tibor
Calhoun, Vince D.
Craddock, R. Cameron
Das, Samir
Duff, Eugene P.
Flandin, Guillaume
Ghosh, Satrajit S.
Glatard, Tristan
Halchenko, Yaroslav O.
Handwerker, Daniel A.
Hanke, Michael
Keator, David
Li, Xiangrui
Michael, Zachary
Maumet, Camille
Nichols, B. Nolan
Nichols, Thomas E.
Pellman, John
Poline, Jean-Baptiste
Rokem, Ariel
Schaefer, Gunnar
Sochat, Vanessa
Triplett, William
Tumer, Jessica A.
Varoquaux, Gael
Poldrack, Russell A.
TI The brain imaging data structure, a format for organizing and describing
outputs of neuroimaging experiments
SO SCIENTIFIC DATA
LA English
DT Article
ID MANAGEMENT; PROVENANCE; STORAGE
AB The development of magnetic resonance imaging (MRI) techniques has defined modern neuroimaging. Since its inception, tens of thousands of studies using techniques such as functional MRI and diffusion weighted imaging have allowed for the non-invasive study of the brain. Despite the fact that MRI is routinely used to obtain data for neuroscience research, there has been no widely adopted standard for organizing and describing the data collected in an imaging experiment. This renders sharing and reusing data (within or between labs) difficult if not impossible and unnecessarily complicates the application of automatic pipelines and quality assurance protocols. To solve this problem, we have developed the Brain Imaging Data Structure (BIDS), a standard for organizing and describing MRI datasets. The BIDS standard uses file formats compatible with existing software, unifies the majority of practices already common in the field, and captures the metadata necessary for most common data processing operations.
C1 [Gorgolewski, Krzysztof J.; Schaefer, Gunnar; Triplett, William; Poldrack, Russell A.] Stanford Univ, Dept Psychol, Stanford, CA 94305 USA.
[Auer, Tibor] MRC, Cognit & Brain Sci Unit, Cambridge CB2 7EF, England.
[Calhoun, Vince D.; Tumer, Jessica A.] Mind Res Network, Albuquerque, NM 87131 USA.
[Calhoun, Vince D.] Univ New Mexico, Dept Elect & Comp Engn, Albuquerque, NM 87106 USA.
[Craddock, R. Cameron] Nathan S Kline Inst Psychiat Res, Computat Neuroimaging Lab, Ctr Biomed Imaging & Neuromodulat, Orangeburg, NY 10962 USA.
[Craddock, R. Cameron; Pellman, John] Child Mind Inst, Ctr Developing Brain, New York, NY 10022 USA.
[Das, Samir; Glatard, Tristan] Montreal Neurol Inst, McGill Ctr Integrat Neurosci, Ludmer Ctr, Montreal, PQ H3A 2B4, Canada.
[Duff, Eugene P.] Univ Oxford, FMRIB Ctr, Oxford OX3 9DU, England.
[Flandin, Guillaume] UCL, Wellcome Trust Ctr Neuroimaging, London WC1N 3BG, England.
[Ghosh, Satrajit S.] MIT, McGovern Inst Brain Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA.
[Ghosh, Satrajit S.] Harvard Med Sch, Dept Otol & Laryngol, Boston, MA 02114 USA.
[Glatard, Tristan] Univ Claude Bernard Lyon 1, Univ Lyon, CNRS UMR5220, CREATIS,Inserm U1044,INSA Lyon, F-69100 Villeurbanne, France.
[Halchenko, Yaroslav O.] Dartmouth Coll, Dept Psychol & Brain Sci, Hanover, NH 03755 USA.
[Handwerker, Daniel A.] NIH, Intramural Res Program, Bethesda, MD 20814 USA.
[Hanke, Michael] Otto Von Guericke Univ, Dept Psychol, D-39016 Magdeburg, Germany.
[Hanke, Michael] Ctr Behav Brain Sci, D-39118 Magdeburg, Germany.
[Keator, David] Univ Calif Irvine, Dept Psychiat & Human Behav, Irvine, CA 92697 USA.
[Li, Xiangrui] Ohio State Univ, Ctr Cognit & Behav Brain Imaging, Columbus, OH 43210 USA.
[Michael, Zachary] Squishymedia, Portland, OR 97232 USA.
[Maumet, Camille; Nichols, Thomas E.] Univ Warwick, WMG, Coventry CV4 7AL, W Midlands, England.
[Nichols, B. Nolan] SRI Int, Ctr Hlth Sci, Menlo Pk, CA 94025 USA.
[Nichols, B. Nolan] Stanford Univ, Dept Psychiat & Behav Sci, Stanford, CA 94304 USA.
[Nichols, Thomas E.] Univ Warwick, Dept Stat, Coventry CV4 7AL, W Midlands, England.
[Poline, Jean-Baptiste] Univ Calif Berkeley, Helen Wills Neurosci Inst, Henry Wheeler Jr Brain Imaging Ctr, Berkeley, CA 94720 USA.
[Rokem, Ariel] Univ Washington, eSci Inst, Seattle, WA 98195 USA.
[Schaefer, Gunnar] Flywheel Exchange LLC, Minneapolis, MN 55405 USA.
[Sochat, Vanessa] Stanford Univ, Program Biomed Informat, Stanford, CA 94305 USA.
[Tumer, Jessica A.] Georgia State Univ, Dept Psychol, Atlanta, GA 30302 USA.
[Tumer, Jessica A.] Georgia State Univ, Neurosci Inst, Atlanta, GA 30302 USA.
[Varoquaux, Gael] INRIA Saclay, Parietal Team, F-91120 Palaiseau, France.
RP Gorgolewski, KJ (reprint author), Stanford Univ, Dept Psychol, Stanford, CA 94305 USA.
EM krzysztof.gorgolewski@gmail.com
RI Glatard, Tristan/H-3656-2014;
OI Duff, Eugene/0000-0001-8795-5472; Ghosh, Satrajit/0000-0002-5312-6729;
Hanke, Michael/0000-0001-6398-6370; Craddock,
Cameron/0000-0002-4950-1303; Nichols, Nolan/0000-0003-1099-3328
FU International Neuroinformatics Coordinating Facility (INCF); Laura and
John Arnold Foundation; NIH [P20GM103472]; Wellcome Trust; NIH NIAAA [1
U01 AA021697]; NIH NIAAA OD [1 U01 AA021697-04S1]; Intramural Research
Program of the NIMH; German federal state of Sachsen-Anhalt; European
Regional Development Fund (ERDF); Medical Research Council (United
Kingdom) [MC-A060-53144]; NSF [1429999]
FX This work has been supported by the International Neuroinformatics
Coordinating Facility (INCF) and by the Laura and John Arnold
Foundation. V.D.C. has been supported by in part by NIH P20GM103472.
T.E.N. and C.M. have been supported by the Wellcome Trust. N.N. has been
supported by NIH NIAAA [1 U01 AA021697]. J.-B.P., B.N.N., and R.A.P.
have been supported by NIH NIAAA OD [1 U01 AA021697-04S1]. D.A.H. was
supported by the Intramural Research Program of the NIMH. M.H. was
supported by the German federal state of Sachsen-Anhalt and the European
Regional Development Fund (ERDF), project: Center for Behavioral Brain
Sciences (CBBS). T.A. was supported by the Medical Research Council
(United Kingdom) [MC-A060-53144]. Y.O.H. has been supported by in part
by NSF [1429999].
NR 29
TC 15
Z9 15
U1 1
U2 1
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2052-4463
J9 SCI DATA
JI Sci. Data
PD JUN 21
PY 2016
VL 3
AR UNSP 160044
DI 10.1038/sdata.2016.44
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EF3JI
UT WOS:000390220200004
PM 27326542
ER
PT J
AU Zeng, C
Guo, XY
Long, JR
Kuchenbaecker, KB
Droit, A
Michailidou, K
Ghoussaini, M
Kar, S
Freeman, A
Hopper, JL
Milne, RL
Bolla, MK
Wang, Q
Dennis, J
Agata, S
Ahmed, S
Aittomaki, K
Andrulis, IL
Anton-Culver, H
Antonenkova, NN
Arason, A
Arndt, V
Arun, BK
Arver, B
Bacot, F
Barrowdale, D
Baynes, C
Beeghly-Fadiel, A
Benitez, J
Bermisheva, M
Blomqvist, C
Blot, WJ
Bogdanova, NV
Bojesen, SE
Bonanni, B
Borresen-Dale, AL
Brand, JS
Brauch, H
Brennan, P
Brenner, H
Broeks, A
Bruning, T
Burwinkel, B
Buys, SS
Cai, QY
Caldes, T
Campbell, I
Carpenter, J
Chang-Claude, J
Choi, JY
Claes, KBM
Clarke, C
Cox, A
Cross, SS
Czene, K
Daly, MB
de la Hoya, M
De Leeneer, K
Devilee, P
Diez, O
Domchek, SM
Doody, M
Dorfling, CM
Dork, T
dos-Santos-Silva, I
Dumont, M
Dwek, M
Dworniczak, B
Egan, K
Eilber, U
Einbeigi, Z
Ejlertsen, B
Ellis, S
Frost, D
Lalloo, F
Fasching, PA
Figueroa, J
Flyger, H
Friedlander, M
Friedman, E
Gambino, G
Gao, YT
Garber, J
Garcia-Closas, M
Gehrig, A
Damiola, F
Lesueur, F
Mazoyer, S
Stoppa-Lyonnet, D
Giles, GG
Godwin, AK
Goldgar, DE
Gonzalez-Neira, A
Greene, MH
Guenel, P
Haeberle, L
Haiman, CA
Hallberg, E
Hamann, U
Hansen, TVO
Hart, S
Hartikainen, JM
Hartman, M
Hassan, N
Healey, S
Hogervorst, FBL
Verhoef, S
Hendricks, CB
Hillemanns, P
Hollestelle, A
Hulick, PJ
Hunter, DJ
Imyanitov, EN
Isaacs, C
Ito, H
Jakubowska, A
Janavicius, R
Jaworska-Bieniek, K
Jensen, UB
John, EM
Beauparlant, CJ
Jones, M
Kabisch, M
Kang, D
Karlan, BY
Kauppila, S
Kerin, MJ
Khan, S
Khusnutdinova, E
Knight, JA
Konstantopoulou, I
Kraft, P
Kwong, A
Laitman, Y
Lambrechts, D
Lazaro, C
Le Marchand, L
Lee, CN
Lee, MH
Lester, J
Li, JM
Liljegren, A
Lindblom, A
Lophatananon, A
Lubinski, J
Mai, PL
Mannermaa, A
Manoukian, S
Margolin, S
Marme, F
Matsuo, K
McGuffog, L
Meindl, A
Menegaux, F
Montagna, M
Muir, K
Mulligan, AM
Nathanson, KL
Neuhausen, SL
Nevanlinna, H
Newcomb, PA
Nord, S
Nussbaum, RL
Offit, K
Olah, E
Olopade, OI
Olswold, C
Osorio, A
Papi, L
Park-Simon, TW
Paulsson-Karlsson, Y
Peeters, S
Peissel, B
Peterlongo, P
Peto, J
Pfeiler, G
Phelan, CM
Presneau, N
Radice, P
Rahman, N
Ramus, SJ
Rashid, MU
Rennert, G
Rhiem, K
Rudolph, A
Salani, R
Sangrajrang, S
Sawyer, EJ
Schmidt, MK
Schmutzler, RK
Schoemaker, MJ
Schurmann, P
Seynaeve, C
Shen, CY
Shrubsole, MJ
Shu, XO
Sigurdson, A
Singer, CF
Slager, S
Soucy, P
Southey, M
Steinemann, D
Swerdlow, A
Szabo, CI
Tchatchou, S
Teixeira, MR
Teo, SH
Terry, MB
Tessier, DC
Teule, A
Thomassen, M
Tihomirova, L
Tischkowitz, M
Toland, AE
Tung, N
Turnbull, C
van den Ouweland, AMW
van Rensburg, EJ
ven den Berg, D
Vijai, J
Wang-Gohrke, S
Weitzel, JN
Whittemore, AS
Winqvist, R
Wong, TY
Wu, AH
Yannoukakos, D
Yu, JC
Pharoah, PDP
Hall, P
Chenevix-Trench, G
Dunning, AM
Simard, J
Couch, FJ
Antoniou, AC
Easton, DF
Zheng, W
AF Zeng, Chenjie
Guo, Xingyi
Long, Jirong
Kuchenbaecker, Karoline B.
Droit, Arnaud
Michailidou, Kyriaki
Ghoussaini, Maya
Kar, Siddhartha
Freeman, Adam
Hopper, John L.
Milne, Roger L.
Bolla, Manjeet K.
Wang, Qin
Dennis, Joe
Agata, Simona
Ahmed, Shahana
Aittomaki, Kristiina
Andrulis, Irene L.
Anton-Culver, Hoda
Antonenkova, Natalia N.
Arason, Adalgeir
Arndt, Volker
Arun, Banu K.
Arver, Brita
Bacot, Francois
Barrowdale, Daniel
Baynes, Caroline
Beeghly-Fadiel, Alicia
Benitez, Javier
Bermisheva, Marina
Blomqvist, Carl
Blot, William J.
Bogdanova, Natalia V.
Bojesen, Stig E.
Bonanni, Bernardo
Borresen-Dale, Anne-Lise
Brand, Judith S.
Brauch, Hiltrud
Brennan, Paul
Brenner, Hermann
Broeks, Annegien
Bruening, Thomas
Burwinkel, Barbara
Buys, Saundra S.
Cai, Qiuyin
Caldes, Trinidad
Campbell, Ian
Carpenter, Jane
Chang-Claude, Jenny
Choi, Ji-Yeob
Claes, Kathleen B. M.
Clarke, Christine
Cox, Angela
Cross, Simon S.
Czene, Kamila
Daly, Mary B.
de la Hoya, Miguel
De Leeneer, Kim
Devilee, Peter
Diez, Orland
Domchek, Susan M.
Doody, Michele
Dorfling, Cecilia M.
Doerk, Thilo
dos-Santos-Silva, Isabel
Dumont, Martine
Dwek, Miriam
Dworniczak, Bernd
Egan, Kathleen
Eilber, Ursula
Einbeigi, Zakaria
Ejlertsen, Bent
Ellis, Steve
Frost, Debra
Lalloo, Fiona
Fasching, Peter A.
Figueroa, Jonine
Flyger, Henrik
Friedlander, Michael
Friedman, Eitan
Gambino, Gaetana
Gao, Yu-Tang
Garber, Judy
Garcia-Closas, Montserrat
Gehrig, Andrea
Damiola, Francesca
Lesueur, Fabienne
Mazoyer, Sylvie
Stoppa-Lyonnet, Dominique
Giles, Graham G.
Godwin, Andrew K.
Goldgar, David E.
Gonzalez-Neira, Anna
Greene, Mark H.
Guenel, Pascal
Haeberle, Lothar
Haiman, Christopher A.
Hallberg, Emily
Hamann, Ute
Hansen, Thomas V. O.
Hart, Steven
Hartikainen, Jaana M.
Hartman, Mikael
Hassan, Norhashimah
Healey, Sue
Hogervorst, Frans B. L.
Verhoef, Senno
Hendricks, Carolyn B.
Hillemanns, Peter
Hollestelle, Antoinette
Hulick, Peter J.
Hunter, David J.
Imyanitov, Evgeny N.
Isaacs, Claudine
Ito, Hidemi
Jakubowska, Anna
Janavicius, Ramunas
Jaworska-Bieniek, Katarzyna
Jensen, Uffe Birk
John, Esther M.
Beauparlant, Charles Joly
Jones, Michael
Kabisch, Maria
Kang, Daehee
Karlan, Beth Y.
Kauppila, Saila
Kerin, Michael J.
Khan, Sofia
Khusnutdinova, Elza
Knight, Julia A.
Konstantopoulou, Irene
Kraft, Peter
Kwong, Ava
Laitman, Yael
Lambrechts, Diether
Lazaro, Conxi
Le Marchand, Loic
Lee, Chuen Neng
Lee, Min Hyuk
Lester, Jenny
Li, Jingmei
Liljegren, Annelie
Lindblom, Annika
Lophatananon, Artitaya
Lubinski, Jan
Mai, Phuong L.
Mannermaa, Arto
Manoukian, Siranoush
Margolin, Sara
Marme, Frederik
Matsuo, Keitaro
McGuffog, Lesley
Meindl, Alfons
Menegaux, Florence
Montagna, Marco
Muir, Kenneth
Mulligan, Anna Marie
Nathanson, Katherine L.
Neuhausen, Susan L.
Nevanlinna, Heli
Newcomb, Polly A.
Nord, Silje
Nussbaum, Robert L.
Offit, Kenneth
Olah, Edith
Olopade, Olufunmilayo I.
Olswold, Curtis
Osorio, Ana
Papi, Laura
Park-Simon, Tjoung-Won
Paulsson-Karlsson, Ylva
Peeters, Stephanie
Peissel, Bernard
Peterlongo, Paolo
Peto, Julian
Pfeiler, Georg
Phelan, Catherine M.
Presneau, Nadege
Radice, Paolo
Rahman, Nazneen
Ramus, Susan J.
Rashid, Muhammad Usman
Rennert, Gad
Rhiem, Kerstin
Rudolph, Anja
Salani, Ritu
Sangrajrang, Suleeporn
Sawyer, Elinor J.
Schmidt, Marjanka K.
Schmutzler, Rita K.
Schoemaker, Minouk J.
Schuermann, Peter
Seynaeve, Caroline
Shen, Chen-Yang
Shrubsole, Martha J.
Shu, Xiao-Ou
Sigurdson, Alice
Singer, Christian F.
Slager, Susan
Soucy, Penny
Southey, Melissa
Steinemann, Doris
Swerdlow, Anthony
Szabo, Csilla I.
Tchatchou, Sandrine
Teixeira, Manuel R.
Teo, Soo H.
Terry, Mary Beth
Tessier, Daniel C.
Teule, Alex
Thomassen, Mads
Tihomirova, Laima
Tischkowitz, Marc
Toland, Amanda E.
Tung, Nadine
Turnbull, Clare
van den Ouweland, Ans M. W.
van Rensburg, Elizabeth J.
ven den Berg, David
Vijai, Joseph
Wang-Gohrke, Shan
Weitzel, Jeffrey N.
Whittemore, Alice S.
Winqvist, Robert
Wong, Tien Y.
Wu, Anna H.
Yannoukakos, Drakoulis
Yu, Jyh-Cherng
Pharoah, Paul D. P.
Hall, Per
Chenevix-Trench, Georgia
Dunning, Alison M.
Simard, Jacques
Couch, Fergus J.
Antoniou, Antonis C.
Easton, Douglas F.
Zheng, Wei
CA EMBRACE
GEMO Study Collaborators
HEBON
KConFab
AOCS Investigators
TI Identification of independent association signals and putative
functional variants for breast cancer risk through fine-scale mapping of
the 12p11 locus
SO BREAST CANCER RESEARCH
LA English
DT Article
DE Fine-scale mapping; Genetic risk factor; PTHLH; CCDC91; Breast cancer;
BRAC1 mutation carriers
ID HORMONE-RELATED PROTEIN; GENOME-WIDE ASSOCIATION; BRCA2 MUTATION
CARRIERS; SUSCEPTIBILITY LOCI; GENETIC MODIFIERS; OVARIAN-CANCER;
LOCALIZATION; METASTASIS; EXPRESSION; ENHANCERS
AB Background: Multiple recent genome-wide association studies (GWAS) have identified a single nucleotide polymorphism (SNP), rs10771399, at 12p11 that is associated with breast cancer risk.
Method: We performed a fine-scale mapping study of a 700 kb region including 441 genotyped and more than 1300 imputed genetic variants in 48,155 cases and 43,612 controls of European descent, 6269 cases and 6624 controls of East Asian descent and 1116 cases and 932 controls of African descent in the Breast Cancer Association Consortium (BCAC; http://bcac.ccge.medschl.cam.ac.uk/), and in 15,252 BRCA1 mutation carriers in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Stepwise regression analyses were performed to identify independent association signals. Data from the Encyclopedia of DNA Elements project (ENCODE) and the Cancer Genome Atlas (TCGA) were used for functional annotation.
Results: Analysis of data from European descendants found evidence for four independent association signals at 12p11, represented by rs7297051 (odds ratio (OR) = 1.09, 95 % confidence interval (CI) = 1.06-1.12; P = 3 x 10(-9)), rs805510 (OR = 1.08, 95 % CI = 1.04-1.12, P = 2 x 10(-5)), and rs1871152 (OR = 1.04, 95 % CI = 1.02-1.06; P = 2 x 10(-4)) identified in the general populations, and rs113824616 (P = 7 x 10(-5)) identified in the meta-analysis of BCAC ER-negative cases and BRCA1 mutation carriers. SNPs rs7297051, rs805510 and rs113824616 were also associated with breast cancer risk at P < 0.05 in East Asians, but none of the associations were statistically significant in African descendants. Multiple candidate functional variants are located in putative enhancer sequences. Chromatin interaction data suggested that PTHLH was the likely target gene of these enhancers. Of the six variants with the strongest evidence of potential functionality, rs11049453 was statistically significantly associated with the expression of PTHLH and its nearby gene CCDC91 at P < 0.05.
Conclusion: This study identified four independent association signals at 12p11 and revealed potentially functional variants, providing additional insights into the underlying biological mechanism(s) for the association observed between variants at 12p11 and breast cancer risk.
C1 [Zeng, Chenjie; Guo, Xingyi; Long, Jirong; Beeghly-Fadiel, Alicia; Blot, William J.; Cai, Qiuyin; Shrubsole, Martha J.; Shu, Xiao-Ou; Zheng, Wei] Vanderbilt Univ, Sch Med, Vanderbilt Ingram Canc Ctr, Div Epidemiol,Dept Med, 2525 West End Ave,8th Floor, Nashville, TN 37203 USA.
[Kuchenbaecker, Karoline B.; Michailidou, Kyriaki; Bolla, Manjeet K.; Wang, Qin; Dennis, Joe; Barrowdale, Daniel; Ellis, Steve; Frost, Debra; McGuffog, Lesley; Pharoah, Paul D. P.; Antoniou, Antonis C.; Easton, Douglas F.; EMBRACE] Univ Cambridge, Dept Publ Hlth & Primary Care, Ctr Canc Genet Epidemiol, Cambridge, England.
[Droit, Arnaud; Hall, Per] Univ Laval, Prote Ctr, CHU Quebec Res Ctr, Quebec City, PQ G1K 7P4, Canada.
[Droit, Arnaud; Hall, Per] Univ Laval, Dept Mol Med, Quebec City, PQ G1K 7P4, Canada.
[Ghoussaini, Maya; Kar, Siddhartha] Univ Cambridge, Dept Oncol, Ctr Canc Genet Epidemiol, Cambridge CB1 8RN, England.
[Freeman, Adam] St Vincent Hosp, Dept Surg, Melbourne, Vic, Australia.
[Hopper, John L.; Milne, Roger L.; Giles, Graham G.] Univ Melbourne, Melbourne Sch Populat & Global Hlth, Ctr Epidemiol & Biostat, Melbourne, Vic, Australia.
[Milne, Roger L.; Giles, Graham G.] Canc Council Victoria, Canc Epidemiol Ctr, Melbourne, Vic, Australia.
[Godwin, Andrew K.; Couch, Fergus J.] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA.
[Agata, Simona; Montagna, Marco] IRCCS, IOV, Immunol & Mol Oncol Unit, Padua, Italy.
[Ahmed, Shahana; Baynes, Caroline; Pharoah, Paul D. P.; Dunning, Alison M.; Easton, Douglas F.] Univ Cambridge, Dept Oncol, Ctr Canc Genet Epidemiol, Cambridge, England.
[Aittomaki, Kristiina] Univ Helsinki, Helsinki Univ Hosp, Dept Clin Genet, Helsinki, Finland.
[Andrulis, Irene L.] Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, Toronto, ON, Canada.
[Andrulis, Irene L.] Univ Toronto, Dept Mol Genet, Toronto, ON, Canada.
[Anton-Culver, Hoda] Univ Calif Irvine, Dept Epidemiol, Irvine, CA USA.
[Antonenkova, Natalia N.] NN Alexandrov Res Inst Oncol & Med Radiol, Minsk, Byelarus.
[Arason, Adalgeir] Landspitali Univ Hosp, Dept Pathol, Reykjavik, Iceland.
[Arason, Adalgeir] Univ Iceland, Fac Med, BMC Biomed Ctr, Reykjavik, Iceland.
[Arndt, Volker; Brenner, Hermann] German Canc Res Ctr, Div Clin Epidemiol & Aging Res, Heidelberg, Germany.
[Arun, Banu K.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Arver, Brita; Liljegren, Annelie] Karolinska Univ Hosp, Dept Oncol, Stockholm, Sweden.
[Bacot, Francois; Tessier, Daniel C.] McGill Univ, Montreal, PQ, Canada.
[Bacot, Francois; Tessier, Daniel C.] Genome Quebec Innovat Ctr, Montreal, PQ, Canada.
[Benitez, Javier; Gonzalez-Neira, Anna] Spanish Natl Canc Res Ctr, Human Canc Genet Program, Madrid, Spain.
[Benitez, Javier] Ctr Invest Red Enfermedades Raras, Valencia, Spain.
[Bermisheva, Marina; Khusnutdinova, Elza] Russian Acad Sci, Ufa Sci Ctr, Inst Biochem & Genet, Ufa, Russia.
[Blomqvist, Carl] Univ Helsinki, Helsinki Univ Hosp, Dept Oncol, Helsinki, Finland.
[Blot, William J.] Int Epidemiol Inst, Rockville, MD USA.
[Bogdanova, Natalia V.] Hannover Med Sch, Dept Radiat Oncol, Hannover, Germany.
[Bojesen, Stig E.] Copenhagen Univ Hosp, Herlev Hosp, Copenhagen Gen Populat Study, Herlev, Denmark.
[Bojesen, Stig E.] Copenhagen Univ Hosp, Herlev Hosp, Dept Clin Biochem, Herlev, Denmark.
[Bojesen, Stig E.] Univ Copenhagen, Fac Hlth & Med Sci, Copenhagen, Denmark.
[Bonanni, Bernardo] Ist Europeo Oncol, Div Canc Prevent & Genet, Milan, Italy.
[Borresen-Dale, Anne-Lise; Broeks, Annegien; Nord, Silje] Radiumhosp, Oslo Univ Hosp, Inst Canc Res, Dept Genet, Oslo, Norway.
[Borresen-Dale, Anne-Lise] Univ Oslo, Fac Med, Inst Clin Med, KG Jebsen Ctr Breast Canc Res, Oslo, Norway.
[Brand, Judith S.; Czene, Kamila; Li, Jingmei] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
[Brauch, Hiltrud] Dr Margarete Fischer Bosch Inst Clin Pharmacol, Stuttgart, Germany.
[Brauch, Hiltrud] Univ Tubingen, Tubingen, Germany.
[Brauch, Hiltrud; Brenner, Hermann] German Canc Res Ctr, German Canc Consortium DKTK, Heidelberg, Germany.
[Brennan, Paul] Int Agcy Res Canc, Lyon, France.
[Brenner, Hermann] German Canc Res Ctr, Div Prevent Oncol, Heidelberg, Germany.
[Broeks, Annegien; Schmidt, Marjanka K.] Antoni van Leeuwenhoek Hosp, Netherlands Canc Inst, Amsterdam, Netherlands.
[Bruening, Thomas] Inst Ruhr Univ Bochum, Inst Prevent & Occupat Med German Social Accident, Bochum, Germany.
[Burwinkel, Barbara; Marme, Frederik] Heidelberg Univ, Dept Obstet & Gynecol, Heidelberg, Germany.
[Burwinkel, Barbara] German Canc Res Ctr, Mol Epidemiol Grp, Heidelberg, Germany.
[Buys, Saundra S.] Univ Utah, Sch Med, Dept Med, Huntsman Canc Inst, Salt Lake City, UT USA.
[Caldes, Trinidad; de la Hoya, Miguel] Hosp Clin San Carlos, IdISSC Inst Invest Sanitaria Hosp Clin San Carlos, Mol Oncol Lab, Madrid, Spain.
[Campbell, Ian] Peter MacCallum Canc Ctr, Canc Gene Lab, Melbourne, Vic, Australia.
[Carpenter, Jane] Univ Sydney, Westmead Millennium Inst, Australian Breast Canc Tissue Bank, Sydney, NSW, Australia.
[Chang-Claude, Jenny; Eilber, Ursula; Rudolph, Anja] German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany.
[Chang-Claude, Jenny] Univ Med Ctr Hamburg Eppendorf, UCCH, Hamburg, Germany.
[Choi, Ji-Yeob; Kang, Daehee] Seoul Natl Univ, Coll Med, Dept Prevent Med, Seoul, South Korea.
[Choi, Ji-Yeob; Kang, Daehee] Seoul Natl Univ, Coll Med, Dept Biomed Sci, Seoul, South Korea.
[Choi, Ji-Yeob; Kang, Daehee] Seoul Natl Univ, Canc Res Inst, Seoul, South Korea.
[Claes, Kathleen B. M.; De Leeneer, Kim] Univ Ghent, Ctr Med Genet, Ghent, Belgium.
[Clarke, Christine] Univ Sydney, Westmead Millenium Inst Med Res, Sydney, NSW, Australia.
[Cox, Angela] Univ Sheffield, Dept Oncol, Sheffield Canc Res, Sheffield, S Yorkshire, England.
[Cross, Simon S.] Univ Sheffield, Dept Neurosci, Acad Unit Pathol, Sheffield, S Yorkshire, England.
[Daly, Mary B.] Fox Chase Canc Ctr, Dept Clin Genet, 7701 Burholme Ave, Philadelphia, PA 19111 USA.
[Devilee, Peter] Leiden Univ, Med Ctr, Dept Pathol, Leiden, Netherlands.
[Devilee, Peter] Leiden Univ, Med Ctr, Dept Human Genet, Leiden, Netherlands.
[Diez, Orland] Univ Hosp Vall dHebron, VHIO, Oncogenet Grp, Barcelona, Spain.
[Diez, Orland] Univ Autonoma Barcelona, Barcelona, Spain.
[Domchek, Susan M.; Nathanson, Katherine L.] Univ Penn, Dept Med, Abramson Canc Ctr, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Doody, Michele; Figueroa, Jonine; Garcia-Closas, Montserrat; Sigurdson, Alice] NCI, Div Canc Epidemiol & Genet, Rockville, MD USA.
[Dorfling, Cecilia M.; van Rensburg, Elizabeth J.] Univ Pretoria, Dept Genet, Pretoria, South Africa.
[Doerk, Thilo; Hillemanns, Peter; Park-Simon, Tjoung-Won; Schuermann, Peter] Hannover Med Sch, Clin Obstet & Gynaecol, Hannover, Germany.
[dos-Santos-Silva, Isabel; Peto, Julian] London Sch Hyg & Trop Med, Dept Noncommunicable Dis Epidemiol, London, England.
[Dumont, Martine; Simard, Jacques] Univ Laval, Ctr Hosp Univ Quebec Res Ctr, Genom Ctr, Quebec City, PQ, Canada.
[Dwek, Miriam; Presneau, Nadege] Univ Westminster, Fac Sci & Technol, Dept Biomed Sci, London, England.
[Dworniczak, Bernd] Inst Human Genet, Munster, Germany.
[Egan, Kathleen] H Lee Moffitt Canc Ctr & Res Inst, Div Populat Sci, Tampa, FL USA.
[Einbeigi, Zakaria] Sahlgrens Univ Hosp, Dept Oncol, Gothenburg, Sweden.
[Ejlertsen, Bent] Copenhagen Univ Hosp, Rigshosp, Dept Oncol, Copenhagen, Denmark.
[Lalloo, Fiona] Cent Manchester Univ Hosp NHS Fdn Trust, Manchester Acad Hlth Sci Ctr, Genet Med, Manchester, Lancs, England.
[Fasching, Peter A.; Haeberle, Lothar] Univ Erlangen Nurnberg, Comprehens Canc Ctr Erlangen EMN, Univ Hosp Erlangen, Dept Gynecol & Obstet, Erlangen, Germany.
[Fasching, Peter A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Hematol & Oncol, Los Angeles, CA 90095 USA.
[Flyger, Henrik] Copenhagen Univ Hosp, Herlev Hosp, Dept Breast Surg, Herlev, Denmark.
[Friedlander, Michael] Australia New Zealand GOG, ANZ GOTG Coordinating Ctr, Camperdown, NSW, Australia.
[Friedman, Eitan; Laitman, Yael] Sheba Med Ctr, Susanne Levy Gertner Oncogenet Unit, Tel Hashomer, Israel.
[Gambino, Gaetana] Univ Pisa, Deparment Lab Med, Sect Genet Oncol, Pisa, Italy.
[Gambino, Gaetana] Univ Hosp Pisa, Pisa, Italy.
[Gao, Yu-Tang] Shanghai Canc Inst, Dept Epidemiol, Shanghai, Peoples R China.
[Garber, Judy] Dana Farber Canc Inst, Canc Risk & Prevent Clin, Boston, MA 02115 USA.
[Garcia-Closas, Montserrat; Jones, Michael; Schoemaker, Minouk J.; Swerdlow, Anthony] Inst Canc Res, Div Genet & Epidemiol, London, England.
[Gehrig, Andrea] Univ Wurzburg, Inst Human Genet, Wurzburg, Germany.
[Damiola, Francesca; Mazoyer, Sylvie; Steinemann, Doris] Univ Lyon, CNRS, INSERM, Ctr Rech Cancerol Lyon,U1052,UMR5286, Lyon, France.
[Lesueur, Fabienne] Mines ParisTech, Inst Curie, INSERM, Genet Epidemiol Canc Team,U900, F-75248 Paris, France.
[Stoppa-Lyonnet, Dominique] Inst Curie, Dept Tumor Biol, Paris, France.
[Stoppa-Lyonnet, Dominique] INSERM, Inst Curie, U830, Paris, France.
[Stoppa-Lyonnet, Dominique] Univ Paris 05, Sorbonne Paris Cite, Paris, France.
[GEMO Study Collaborators] UNICANC Genet Grp, Natl Canc Genet Network, GEMO Study, Paris, France.
[Godwin, Andrew K.] Univ Kansas, Med Ctr, Dept Pathol & Lab Med, Kansas City, KS 66103 USA.
[Goldgar, David E.] Univ Utah, Sch Med, Huntsman Canc Inst, Dept Dermatol, Salt Lake City, UT USA.
[Greene, Mark H.; Mai, Phuong L.] NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD USA.
[Guenel, Pascal; Menegaux, Florence] INSERM, Ctr Res Epidemiol & Populat Hlth, Environm Epidemiol Canc, Villejuif, France.
[Guenel, Pascal; Menegaux, Florence] Univ Paris 11, Villejuif, France.
[Haiman, Christopher A.; ven den Berg, David; Wu, Anna H.] Univ Southern Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA.
[Hallberg, Emily; Hart, Steven; Olswold, Curtis; Slager, Susan] Mayo Clin, Dept Hlth Sci Res, Rochester, MN USA.
[Hamann, Ute; Kabisch, Maria; Rashid, Muhammad Usman] German Canc Res Ctr, Mol Genet Breast Canc, Heidelberg, Germany.
[Hansen, Thomas V. O.] Copenhagen Univ Hosp, Rigshosp, Ctr Genom Med, Copenhagen, Denmark.
[Hartikainen, Jaana M.; Mannermaa, Arto] Kuopio Univ Hosp, Ctr Canc, Kuopio, Finland.
[Hartikainen, Jaana M.; Mannermaa, Arto] Univ Eastern Finland, Inst Clin Med Pathol & Forens Med, Kuopio, Finland.
[Hartikainen, Jaana M.; Mannermaa, Arto] Kuopio Univ Hosp, Dept Clin Pathol, Imaging Ctr, Kuopio, Finland.
[Hartman, Mikael; Lee, Chuen Neng] Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore.
[Hartman, Mikael] Natl Univ Hlth Syst, Dept Surg, Singapore, Singapore.
[Hassan, Norhashimah; Teo, Soo H.] Canc Res Initiat Fdn, Subang Jaya, Selangor, Malaysia.
[Hassan, Norhashimah; Teo, Soo H.] Univ Malaya, Med Ctr, Canc Res Inst, Breast Canc Res Unit, Kuala Lumpur, Malaysia.
[Healey, Sue] QIMR Berghofer Med Res Inst, Canc Div, Brisbane, Qld, Australia.
[Hogervorst, Frans B. L.; Verhoef, Senno] Netherlands Canc Inst, Family Canc Clin, Amsterdam, Netherlands.
[HEBON] Netherlands Canc Inst, Coordinating Ctr, Hereditary Breast & Ovarian Canc Res Grp Netherla, Amsterdam, Netherlands.
[Hendricks, Carolyn B.] Suburban Hosp, Bethesda, MD USA.
[Hendricks, Carolyn B.] City Hope Natl Med Ctr, Clin Canc Genet Community Res Network, Duarte, CA USA.
[Hollestelle, Antoinette; Seynaeve, Caroline] Erasmus MC Canc Inst, Family Canc Clin, Dept Med Oncol, Rotterdam, Netherlands.
[Hulick, Peter J.] NorthShore Univ HealthSyst, Ctr Med Genet, Evanston, IL USA.
[Hunter, David J.; Kraft, Peter] Harvard Sch Publ Hlth, Program Genet Epidemiol & Stat Genet, Boston, MA USA.
[Hunter, David J.; Kraft, Peter] Harvard Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.
[Imyanitov, Evgeny N.] NN Petrov Inst Oncol, St Petersburg, Russia.
[Isaacs, Claudine] Georgetown Univ, Lombardi Comprehens Canc Ctr, Washington, DC USA.
[Ito, Hidemi] Aichi Canc Ctr Res Inst, Div Epidemiol & Prevent, Nagoya, Aichi, Japan.
[Jakubowska, Anna; Jaworska-Bieniek, Katarzyna; Lubinski, Jan] Pomeranian Med Univ, Dept Genet & Pathol, Szczecin, Poland.
[Janavicius, Ramunas] State Res Inst, Ctr Innovat Med, Vilnius, Lithuania.
[Jensen, Uffe Birk] Aarhus Univ Hosp, Dept Clin Genet, Aarhus N, Denmark.
[John, Esther M.] Canc Prevent Inst Calif, Dept Epidemiol, Fremont, CA USA.
[John, Esther M.; Whittemore, Alice S.] Stanford Univ, Sch Med, Dept Hlth Res & Policy Epidemiol, Stanford, CA 94305 USA.
[John, Esther M.; Whittemore, Alice S.] Stanford Univ, Sch Med, Stanford Canc Inst, Stanford, CA 94305 USA.
[Beauparlant, Charles Joly] Ctr Hosp Univ Quebec Res Ctr, Genom Ctr, Quebec City, PQ, Canada.
[Beauparlant, Charles Joly] Univ Laval, Quebec City, PQ, Canada.
[Karlan, Beth Y.; Lester, Jenny] Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Inst, Womens Canc Program, Los Angeles, CA 90048 USA.
[Kauppila, Saila] Univ Oulu, Oulu Univ Hosp, Dept Pathol, Oulu, Finland.
[Kerin, Michael J.] Natl Univ Ireland, Sch Med, Galway, Ireland.
[Khan, Sofia; Nevanlinna, Heli] Univ Helsinki, Helsinki Univ Hosp, Dept Obstet & Gynecol, Helsinki, Finland.
[Khusnutdinova, Elza] Bashkir State Univ, Dept Genet & Fundamental Med, Ufa, Russia.
[Knight, Julia A.] Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, Prosserman Ctr Hlth Res, Toronto, ON, Canada.
[Knight, Julia A.] Univ Toronto, Dalla Lana Sch Publ Hlth, Div Epidemiol, Toronto, ON, Canada.
[Konstantopoulou, Irene] Natl Ctr Sci Res Demokritos, IRRP, Mol Diagnost Lab, Athens, Greece.
[Kwong, Ava] Hong Kong Sanat & Hosp, Canc Genet Ctr, Hong Kong Hereditary Breast Canc Family Registry, Hong Kong, Hong Kong, Peoples R China.
[Kwong, Ava] Univ Hong Kong, Dept Surg, Hong Kong, Hong Kong, Peoples R China.
[Lambrechts, Diether] Vesalius Res Ctr, Leuven, Belgium.
[Lambrechts, Diether] Univ Leuven, Dept Oncol, Lab Translat Genet, Leuven, Belgium.
[Lazaro, Conxi] Catalan Inst Oncol, IDIBELL Bellvitge Biomed Res Inst, Hereditary Canc Program, Mol Diagnost Unit, Barcelona, Spain.
[Le Marchand, Loic] Univ Hawaii, Ctr Canc, Honolulu, HI USA.
[Lee, Min Hyuk] Soonchunhyang Univ & Hosp, Dept Surg, Seoul, South Korea.
[Lindblom, Annika] Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden.
[Lophatananon, Artitaya; Muir, Kenneth] Univ Warwick, Warwick Med Sch, Div Hlth Sci, Coventry, W Midlands, England.
[Manoukian, Siranoush; Peissel, Bernard] INT, Fdn IRCCS Ist Ricovero Cura Carattere Sci, Dept Prevent & Predict Med, Unit Med Genet, Milan, Italy.
[Margolin, Sara] Karolinska Inst, Dept Oncol Pathol, Stockholm, Sweden.
[Marme, Frederik] Heidelberg Univ, Natl Ctr Tumor Dis, Heidelberg, Germany.
[Matsuo, Keitaro] Kyushu Univ, Fac Med Sci, Dept Prevent Med, Fukuoka, Japan.
[Meindl, Alfons] Tech Univ Munich, Div Gynaecol & Obstet, Munich, Germany.
[Muir, Kenneth] Univ Manchester, Inst Populat Hlth, Manchester, Lancs, England.
[Mulligan, Anna Marie] Univ Hlth Network, Lab Med Program, Toronto, ON, Canada.
[Mulligan, Anna Marie] Univ Toronto, Dept Lab Med & Pathol, Toronto, ON, Canada.
[Neuhausen, Susan L.] City Hope Natl Med Ctr, Beckman Res Inst, Duarte, CA USA.
[Newcomb, Polly A.] Univ Wisconsin, Carbone Canc Ctr, Madison, WI USA.
[Newcomb, Polly A.] Fred Hutchinson Canc Res Ctr, Canc Prevent Program, Seattle, WA USA.
[Nussbaum, Robert L.] Univ Calif San Francisco, Dept Med Genet, San Francisco, CA 94143 USA.
[Offit, Kenneth; Vijai, Joseph] Mem Sloan Kettering Canc Ctr, Dept Canc Biol & Genet, Clin Genet Res Lab, 1275 York Ave, New York, NY 10021 USA.
[Olah, Edith] Natl Inst Oncol, Dept Mol Genet, Budapest, Hungary.
[Olopade, Olufunmilayo I.] Univ Chicago, Med Ctr, Ctr Clin Canc Genet & Global Hlth, Chicago, IL 60637 USA.
[Osorio, Ana] Spanish Natl Canc Ctr CNIO, Human Canc Genet Program, Human Genet Grp, Madrid, Spain.
[Osorio, Ana] Biomed Network Rare Dis CIBERER, Madrid, Spain.
[Papi, Laura] Univ Florence, Dept Biomed Expt & Clin Sci, Unit Med Genet, Florence, Italy.
[Paulsson-Karlsson, Ylva] Uppsala Univ, Dept Immunol Genet & Pathol, Uppsala, Sweden.
[Peeters, Stephanie] Univ Hosp Gasthuisberg, Leuven, Belgium.
[Peterlongo, Paolo] Fdn Ist FIRC Italian Fdn Canc Res Oncol Mol, IFOM, Milan, Italy.
[Pfeiler, Georg] Med Univ Vienna, Dept Obstet & Gynecol, Vienna, Austria.
[Pfeiler, Georg] Med Univ Vienna, Ctr Comprehens Canc, Vienna, Austria.
[Phelan, Catherine M.] H Lee Moffitt Canc Ctr & Res Inst, Dept Canc Epidemiol, Tampa, FL USA.
[Radice, Paolo] INT, Fdn IRCCS Ist Ricovero & Cura Carattere Sci, Dept Prevent & Predict Med, Unit Mol Bases Genet Risk & Genet Testing, Milan, Italy.
[Rahman, Nazneen; Turnbull, Clare] Inst Canc Res, Sect Canc Genet, London, England.
[Ramus, Susan J.] Univ Southern Calif, Keck Sch Med, Norris Comprehens Canc Ctr, Dept Prevent Med, Los Angeles, CA 90033 USA.
[Rashid, Muhammad Usman] SKMCH & RC, Dept Basic Sci, Lahore, Pakistan.
[Rennert, Gad] Clalit Natl Israeli Canc Control Ctr, Haifa, Israel.
[Rennert, Gad] Carmel Hosp, Dept Community Med & Epidemiol, Haifa, Israel.
[Rennert, Gad] B Rappaport Fac Med, Haifa, Israel.
[Rhiem, Kerstin] Univ Hosp Cologne, Ctr Familial Breast & Ovarian Canc, Dept Obstet & Gynaecol, Cologne, Germany.
[Rhiem, Kerstin] Univ Hosp Cologne, CIO, CMMC, Cologne, Germany.
[Salani, Ritu] Ohio State Univ, Coll Med, Obstet & Gynecol, Columbus, OH 43210 USA.
[Sangrajrang, Suleeporn] Natl Canc Inst, Bangkok, Thailand.
[Sawyer, Elinor J.] Kings Coll London, Guys Hosp, Res Oncol, London, England.
[Schmutzler, Rita K.] Univ Hosp Cologne, Dept Obstet & Gynaecol, Div Mol Gynecooncol, Cologne, Germany.
[Schmutzler, Rita K.] Univ Hosp Cologne, Ctr Familial Breast & Ovarian Canc, Cologne, Germany.
[Schmutzler, Rita K.] Univ Hosp Cologne, Ctr Integrated Oncol, Cologne, Germany.
[Schmutzler, Rita K.] Univ Hosp Cologne, Ctr Mol Med, Cologne, Germany.
[Shen, Chen-Yang] China Med Univ, Sch Publ Hlth, Taichung, Taiwan.
[Shen, Chen-Yang] Acad Sinica, Inst Biomed Sci, Taiwan Biobank, Taipei, Taiwan.
[Singer, Christian F.] Med Univ Vienna, Ctr Comprehens Canc, Dept Obstet & Gynecol, Vienna, Austria.
[Soucy, Penny] Ctr Hosp Univ Quebec Res Ctr, Quebec City, PQ, Canada.
[Soucy, Penny] Univ Laval, Quebec City, PQ, Canada.
[Southey, Melissa] Univ Melbourne, Dept Pathol, Genet Epidemiol Lab, Parkville, Vic, Australia.
[Steinemann, Doris] Hannover Med Sch, Hannover, Germany.
[Swerdlow, Anthony] Inst Canc Res, Div Breast Canc Res, London, England.
[Szabo, Csilla I.] NHGRI, NIH, Bethesda, MD 20892 USA.
[Tchatchou, Sandrine] Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, Toronto, ON, Canada.
[Teixeira, Manuel R.] Portuguese Oncol Inst, Dept Genet, Oporto, Portugal.
[Teixeira, Manuel R.] Univ Porto, Biomed Sci Inst ICBAS, Oporto, Portugal.
[Terry, Mary Beth] Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY USA.
[Teule, Alex] Catalan Inst Oncol, IDIBELL Bellvitge Biomed Res Inst, Hereditary Canc Program, Genet Counseling Unit, Barcelona, Spain.
[Thomassen, Mads] Odense Univ Hosp, Dept Clin Genet, Odense C, Denmark.
[Tihomirova, Laima] Latvian Biomed Res & Study Ctr, Riga, Latvia.
[Tischkowitz, Marc] McGill Univ, Program Canc Genet, Dept Human Genet, Montreal, PQ, Canada.
[Tischkowitz, Marc] McGill Univ, Dept Oncol, Montreal, PQ, Canada.
[Tischkowitz, Marc] Univ Cambridge, Sch Med, Cambridge, England.
[Toland, Amanda E.] Ohio State Univ, Ctr Comprehens Canc, Dept Mol Virol Immunol & Med Genet, Columbus, OH USA.
[Tung, Nadine] Beth Israel Deaconess Med Ctr, Dept Med Oncol, Boston, MA 02215 USA.
[van den Ouweland, Ans M. W.] Erasmus Univ, Med Ctr, Dept Clin Genet, Rotterdam, Netherlands.
[Offit, Kenneth; Vijai, Joseph] Mem Sloan Kettering Canc Ctr, Dept Med, Clin Genet Serv, 1275 York Ave, New York, NY 10021 USA.
[Wang-Gohrke, Shan] Univ Ulm, Dept Obstet & Gynecol, Ulm, Germany.
[Weitzel, Jeffrey N.] City Hope Natl Med Ctr, Clin Canc Genet Community Res Network, Clin Canc Genet, Duarte, CA USA.
[Winqvist, Robert] Univ Oulu, Lab Canc Genet & Tumor Biol, Dept Clin Chem, Oulu, Finland.
[Winqvist, Robert] Univ Oulu, Bioctr Oulu, Oulu, Finland.
[Winqvist, Robert] Ctr NordLab Oulu, Northern Finland Lab, Lab Canc Genet & Tumor Biol, Oulu, Finland.
[Wong, Tien Y.] Natl Univ Singapore, Singapore Eye Res Inst, Singapore, Singapore.
[Yannoukakos, Drakoulis] Aristotle Univ Thessaloniki, Sch Med, Papageorgiou Hosp, Dept Med Oncol, Thessaloniki, Greece.
[Yu, Jyh-Cherng] Natl Taiwan Univ Hosp, Dept Surg, Taipei, Taiwan.
[Chenevix-Trench, Georgia; KConFab] QIMR Berghofer Med Res Inst, Dept Genet, Brisbane, Qld, Australia.
[Chenevix-Trench, Georgia; AOCS Investigators] Univ Melbourne, Peter MacCallum Canc Inst, Melbourne, Vic, Australia.
RP Zheng, W (reprint author), Vanderbilt Univ, Sch Med, Vanderbilt Ingram Canc Ctr, Div Epidemiol,Dept Med, 2525 West End Ave,8th Floor, Nashville, TN 37203 USA.
EM wei.zheng@vanderbilt.edu
RI Peissel, Bernard/E-8187-2017; manoukian, siranoush/E-7132-2017; Bruning,
Thomas/G-8120-2015; Hartikainen, Jaana/E-6256-2015; Osorio,
Ana/I-4324-2014; Li, Jingmei/I-2904-2012; Teo, Soo-hwang/H-2353-2014;
Dork, Thilo/J-8620-2012; Knight, Julia/A-6843-2012; Zheng,
Wei/O-3351-2013; Nord, Silje/R-5212-2016; Khusnutdinova,
Elza/A-4810-2013; Brenner, Hermann/B-4627-2017; Jansen van Rensburg,
Elizabeth (Lizette)/B-9104-2011
OI Peissel, Bernard/0000-0001-9233-3571; Khan, Sofia/0000-0003-4185-8882;
Yannoukakos, Drakoulis/0000-0001-7509-3510; Dunning, Alison
Margaret/0000-0001-6651-7166; Evans, Gareth/0000-0002-8482-5784;
manoukian, siranoush/0000-0002-6034-7562; Bruning,
Thomas/0000-0001-9560-5464; Osorio, Ana/0000-0001-8124-3984; Li,
Jingmei/0000-0001-8587-7511; Zheng, Wei/0000-0003-1226-070X; Nord,
Silje/0000-0002-3271-5356; Brenner, Hermann/0000-0002-6129-1572;
FU charity Against Breast Cancer [1121258]; Deutsche Krebshilfe; NHMRC;
National Breast Cancer Foundation, Cancer Australia; National Institute
of Health (USA); Breakthrough Breast Cancer; Institute of Cancer
Research; NHS; National Cancer Institute grants [CA 27469]; GOG
Statistical and Data Center [CA 37517]; GOG Cancer Prevention and
Control Committee [CA 101165]; Intramural Research Program; NCI; ISCIII
(Spain) [RD12/00369/0006, 12/00539]; European Regional Development FEDER
funds; Dutch Cancer Society [NKI1998-1854, NKI2004-3088, NKI2007-3756,
NKI 2007-3839, 2009 4363]; Netherlands Organization of Scientific
Research [NWO 91109024]; Pink Ribbon [110005, 2014-187.WO76]; BBMRI [NWO
184.021.007/CP46]; Transcan [JTC 2012]; Singapore Breast Cancer Study;
HUKM-HKL; Malaysian Ministry of Science, Technology and Innovation,
Ministry of Higher Education [UM.C/HIR/MOHE/06]; Cancer Research
Initiatives Foundation; NIH [R37CA070867]; Cancer Research UK
[C1287/A10118, C1287/A12014, C1287/A 10710, C12292/A11174, C1281/A12014,
C5047/A8384, C5047/A15007, C5047/A10692, C8197/A16565, C8620/A8372,
C8620/A8857]; European Community Seventh Framework Programme [223175,
HEALTH-F2-2009-223175]; National Institutes of Health [CA128978, R01
CA77398]; Post-Cancer GWAS initiative [1U19 CA148537, 1U19 CA148065,
1U19 CA148112]; Department of Defence [W81XWH-10-1-0341]; Canadian
Institutes of Health Research (CIHR); Komen Foundation; Breast Cancer
Research Foundation; Ovarian Cancer Research Fund; National Cancer
Institute (USA) [UM1 CA164920]; National Health and Medical Research
Council of Australia; New South Wales Cancer Council; Victorian Health
Promotion Foundation (Australia); Victorian Breast Cancer Research
Consortium; BBMRI-NL; Dutch government [NWO 184.021.007]; Dutch National
Genomics Initiative; Cancer Institute NSW; National Breast Cancer
Foundation; Breast Cancer Research Trust, UK; ELAN-Fond of the
University Hospital of Erlangen; Cancer Research UK; National Cancer
Research Network (NCRN); NIHR Comprehensive Biomedical Research Centre;
Guy's & St. Thomas' NHS Foundation Trust in partnership with King's
College London, UK; Oxford Biomedical Research Centre; US Military
Acquisition (ACQ) Activity, Era of Hope Award [W81XWH-05-1-0204];
Institute of Cancer Research (UK); Medical Research Council (UK)
Clinical Research Fellowship; Dietmar-Hopp Foundation; Helmholtz
Society; German Cancer Research Center (DKFZ); Fondation de France;
Institut National du Cancer (INCa); Ligue Nationale contre le Cancer;
Ligue contre le Cancer Grand Ouest; Agence Nationale de Securit,
Sanitaire (ANSES); Agence Nationale de la Recherche (ANR); Chief
Physician Johan Boserup and Lise Boserup Fund; Danish Medical Research
Council and Herlev Hospital; Instituto de Salud Carlos III; Red Tematica
de Investigacion Cooperativa en Cancer; Asociacion Espanola Contra el
Cancer; Fondo de Investigacion Sanitario [PI11/ 00923, PI12/00070];
California Breast Cancer Act; California Breast Cancer Research Fund
[97-10500]; California Department of Public Health as part of the
statewide cancer reporting program mandated by California Health and
Safety Code Section [103885]; Lon V Smith Foundation [LVS39420]; Against
Breast Cancer Registered Charity [1121258]; Baden Wrettemberg Minister
of Sciences, Research and Arts; German Cancer Aid (Deutsche Krebshilfe);
Deutsche Krebshilfe [107 352]; Federal Ministry of Education and
Research (BMBF) Germany grants [01KW9975/5, 01KW9976/8, 01KW9977/0,
01KW0114]; Robert Bosch Foundation; Stuttgart; Deutsches
Krebsforschungszentrum (DKFZ), Heidelberg; Institute for Prevention and
Occupational Medicine of the German Social Accident Insurance; Institute
of the Ruhr University Bochum (IPA), Bochum; Department of Internal
Medicine; Evangelische Kliniken Bonn gGmbH; Johanniter Krankenhaus,
Bonn, Germany; Deutsche Krebshilfe e. V. [70492]; Hannover Medical
School; Helsinki University Central Hospital Research Fund; Academy of
Finland [266528]; Finnish Cancer Society; Nordic Cancer Union; Sigrid
Juselius Foundation; Ministry of Education, Science, Sports, Culture and
Technology of Japan; Ministry of Health, Labor and Welfare of Japan;
Health and Labor Sciences Research Grants for Research on Applying
Health Technology from the Ministry Health, Labor and Welfare of Japan;
National Cancer Center Research and Development Fund; Takeda Health
Foundation; Friends of Hannover Medical School; Rudolf Bartling
Foundation; German Federal Ministry of Research and Education
[RUS08/017]; Stockholm County Council; Karolinska Institutet; Swedish
Cancer Society; Gustav V Jubilee foundation; Bert von Kantzows
foundation; special Government Funding (EVO) of Kuopio University
Hospital grants; Cancer Fund of North Savo; Finnish Cancer Organizations
and strategic funding of the University of Eastern Finland; National
Health and Medical Research Council (NHMRC); Queensland Cancer Fund;
Cancer Councils of New South Wales, Victoria, Tasmania and South
Australia; Cancer Foundation of Western Australia; United States Army
Medical Research and Materiel Command [DAMD17-01-1-0729]; Cancer Council
Victoria; Cancer Council New South Wales; Cancer Council South
Australia; Cancer Council Tasmania; National Health and Medical Research
Council of Australia (NHMRC) [400413, 400281, 199600]; California Breast
Cancer Research Program [1RB-0287, 3 PB-0102, 5 PB-0018, 10 PB-0098];
California Department of Health; National Cancer Institute Division of
Cancer Prevention and Control Surveillance, Epidemiology, and End
Results Program [N01CN25403]; Stichting tegen Kanker [232-2008,
196-2010]; FWO; Deutsche Krebshilfe e.V. [70-2892-BR I, 106332, 108253,
108419]; Hamburg Cancer Society; Federal Ministry of Education and
Research (BMBF) Germany [01KH0402]; Italian Association for Cancer
Research (AIRC); Italian citizens [5/1000]; NIH grants [CA128978,
CA116167, CA176785, CA116201, CA63464, CA54281, CA098758, CA132839];
Ting Tsung and Wei Fong Chao Foundation; VicHealth and Cancer Council
Victoria; Australian NHMRC grants [209057, 251553, 504711]; Robert and
Kate Niehaus Clinical Cancer Genetics Initiative; Quebec Breast Cancer
Foundation; Canadian Institutes of Health Research for the CIHR Team in
Familial Risks of Breast Cancer program [CRN-87521]; Ministry of
Economic Development, Innovation and Export Trade [PSR-SIIRI-701];
Malaysian Ministry of Science, Technology and Innovation (MOSTI);
Malaysian Ministry of Higher Education [UM.C/HlR/MOHE/06]; Cancer
Research Initiatives Foundation (CARIF); Biomedical Research Council,
Singapore [BMRC08/1/35/19/550]; National medical Research Council,
Singapore [NMRC/CG/SERI/2010]; K.G. Jebsen Centre for Breast Cancer
Research; Research Council of Norway grant [193387/V50, 193387/H10];
South Eastern Norway Health Authority [39346]; Norwegian Cancer Society;
NIH grant [R01CA100374, CA87969, R01CA64277, R01CA148667, R37CA70867];
Finnish Cancer Foundation; Center of Excellence grant [251314];
University of Oulu; University of Oulu Support Foundation; special
Governmental EVO funds; Biobanking and Biomolecular Resources Research
Infrastructure [BBMRI-NL CP16]; Intramural Research Funds of the
National Cancer Institute, Department of Health and Human Services, USA;
Marit and Hans Rausings Initiative Against Breast Cancer; Agency for
Science, Technology and Research of Singapore (A*STAR); US National
Institute of Health (NIH); Susan G. Komen Breast Cancer Foundation;
Genetic Associations and Mechanisms in Oncology (GAME-ON) Network [U19
CA148065]; Yorkshire Cancer Research [S295, S299, S305PA]; Sheffield
Experimental Cancer Medicine Centre; National Program of Cancer
Registries, Centers for Disease Control and Prevention (CDC); UK
National Institute for Health Research Biomedical Research Centre at the
University of Cambridge; BRL (Basic Research Laboratory) programme
through the National Research Foundation of Korea - Ministry of
Education, Science and Technology [2012-0000347]; NUS start-up Grant;
National University Cancer Institute Singapore (NCIS) Centre Grant; NMRC
Clinician Scientist Award; Biomedical Research Council [05/1/21/19/425];
DKFZ; National Cancer Institute Thailand; Specialized Program of
Research Excellence (SPORE) in Breast Cancer [CA116201]; Stefanie
Spielman Breast Cancer fund; OSU Comprehensive Cancer Center; Hellenic
Cooperative Oncology Group research grant [HR R_BG/04]; Greek General
Secretary for Research and Technology (GSRT) Program; Research
Excellence II; European Union (European Social Fund - ESF); Greek
national funds through the Operational Program "Education and Lifelong
Learning" of the National Strategic Reference Framework (NSRF) -
ARISTEIA; Taiwan Biobank project of the Institute of Biomedical
Sciences, Academia Sinica, Taiwan; Institute of Cancer Research (ICR),
London; Massachusetts [R01CA47305]; Wisconsin [R01 CA47147]; New
Hampshire centres [R01CA69664]; Intramural Research Program of the
Division of Cancer Epidemiology and Genetics; National Cancer Institute;
National Institutes of Health; U.S. Department of Health and Human
Services; National Cancer Institute [CA164920]; Lithuania (BFBOCC-LT),
Research Council of Lithuania grant [LIG-07/2012]; Cancer Association of
South Africa (CANSA); Morris and Horowitz Families Endowed
Professorship; NEYE Foundation; Spanish Association against Cancer
[AECC08]; RTICC [06/0020/1060, FISPI08/1120]; Mutua Madrilena Foundation
(FMMA) [SAF2010-20493]; Office of the Director, National Institutes of
Health; Fondazione IRCCS Istituto Nazionale Tumori [5x1000]; FiorGen
Foundation for Pharmacogenomics; Cancer Research UK grants
[C1287/A10118, C12292/A11174]; NHMRC Program Grant; Greek national funds
through the Operational Program "Education and Lifelong Learning" of the
National Strategic Reference Framework (NSRF) - Research Funding Program
of the General Secretariat for Research Technology [SYN11_10_19 NBCA];
NIHR grant; NIHR support; Royal Marsden NHS Foundation Trust; University
of Kansas Cancer Center [P30 CA168524]; Kansas Bioscience Authority
Eminent Scholar Program; Chancellors Distinguished Chair in Biomedical
Sciences Professorship; German Consortium of Hereditary Breast and
Ovarian Cancer (GC-HBOC); German Cancer Aid [109076]; Center for
Molecular Medicine Cologne (CMMC); Association "Le cancer du sein,
parlons-en!" Award; Canadian Institutes of Health Research for the "CIHR
Team in Familial Risks of Breast Cancer" program; French National
Institute of Cancer (INCa); Non-Therapeutic Subject Registry Shared
Resource at Georgetown University (NIH/NCI) [P30-CA051008]; Fisher
Center for Familial Cancer Research; Swing For the Cure; GOA grant
[BOF10/GOA/019]; Ghent University Hospital; Helsinki University Hospital
Research Fund; Dutch Cancer Society grants [NKI1998-1854, NKI2004-3088,
NKI2007-3756]; Netherlands Organization of Scientific Research grant
[NWO 91109024]; Pink Ribbon grant [110005]; BBMRI grant NWO
[184.021.007/CP46]; Hong Kong Hereditary Breast Cancer Family Registry;
Dr. Ellen Li Charitable Foundation, Hong Kong; Hungarian Research Grants
[KTIA-OTKA CK-80745, OTKA K-112228]; Norwegian EEA Financial Mechanism
[Hu0115/NA/2008-3/OP-9]; ICO: contract grant sponsor; ISCIIIRETIC
[RD06/0020/1051, RD12/0036/008, PI10/01422, PI10/00748, PI13/00285,
PIE13/00022, 2009SGR290, 2014SGR364]; Icelandic Association "Walking for
Breast Cancer Research"; Landspitali University Hospital Research Fund;
Canadian Institutes of Health Research for the "CIHR Team in Familial
Risks of Breast Cancer" programme; Canadian Breast Cancer Research
Alliance-grant [019511]; Ministry of Economic Development, Innovation
and Export Trade - grant [PSR-SIIRI-701]; Ministero della Salute and
Istituto Oncologico Veneto grant [5x1000]; Liga Portuguesa Contra o
Cancro; National R&D Program for Cancer Control, Ministry for Health,
Welfare and Family Affairs, Republic of Korea [1020350]; NCI Specialized
Program of Research Excellence (SPORE) in Breast Cancer [CA116201]; U.S.
Department of Defence Ovarian Cancer Idea award [W81XWH-10-1-0341]; MH
CZ - DRO (MMCI) [00209805]; European Regional Development Fund; State
Budget of the Czech Republic (RECAMO) [CZ.1.05/2.1.00/03.0101]; Charles
University in Prague project [UNCE204024]; Andrew Sabin Research Fund;
Intramural Research Program of the US National Cancer Institute, NIH;
Westat Inc, Rockville [NO2-CP-11019-50, N02-CP-65504]; Clalit Health
Services in Israel; Israel Cancer Association; Breast Cancer Research
Foundation (BCRF), NY; Russian Federation for Basic Research
[13-04-92613, 14-04-93959, 15-04-01744]; National Cancer Institute
grants; Tissue Bank [CA 27469]; NRG Oncology Statistical and Data Center
[CA 37517]; NRG Oncology's Cancer Prevention and Control Committee [CA
101165]; Intramural Research Program, NCI; Ohio State University
Comprehensive Cancer Center; ITT (Istituto Toscano Tumori) grants;
Ministry of Science, Technology and Innovation, Ministry of Higher
Education [UM.C/HlR/MOHE/06]; Ralph and Marion Falk Medical Research
Trust; Entertainment Industry Fund National Women's Cancer Research
Alliance; Jonsson Comprehensive Cancer Center Foundation; UCSF Cancer
Risk Program and Helen Diller Family Comprehensive Cancer Center; CRUK;
National Institutes of Health (NIH) [R01-CA102776, R01-CA083855]; Susan
G. Komen Foundation for the cure, Basser Research Center for BRCA;
Frieda G. and Saul F. Shapira BRCA-Associated Cancer Research Program;
Ovarian Cancer Research Fund (OCRF) grant [258807]; Ann Schreiber
Program of Excellence award from the Ovarian Cancer Research Fund
[POE/USC/01.12]; National Institute of Health [5 U19 CA148112-02];
Cancer Center Support Grant from the National Cancer Institute [P30
CA014089]; Victorian Cancer Agency, Cancer Australia, National Breast
Cancer Foundation; American Cancer Society Early Detection Professorship
[SIOP-06-258-01-COUN]; National Center for Advancing Translational
Sciences (NCATS) [UL1TR000124]; [KULPFV/10/016-SymBioSysII]; [P30
CA68485]; [PBZ_KBN_122/P05/2004]; [5U01CA113916]; [R01CA140323]
FX We thank all the individuals who took part in these studies and all the
researchers, study staff, clinicians and other healthcare providers,
technicians and administrative staff who have enabled this work to be
carried out. In particular, we would like to thank Terence Jack Martin
(St Vincents Institute, Melbourne, Australia) for carefully reviewing
this manuscript. COGS would not have been possible without the
contributions of the following: Andrew Berchuck (OCAC), Rosalind A.
Eeles, Ali Amin Al Olama, Zsofia Kote-Jarai, Sara Benlloch (PRACTICAL),
Lesley McGuffog, Andrew Lee, and Ed Dicks, Craig Luccarini and the staff
of the Centre for Genetic Epidemiology Laboratory, Javier Benitez, Anna
Gonzalez-Neira and the staff of the CNIO genotyping unit, and Daniel C.
Tessier, Francois Bacot, Daniel Vincent, Sylvie LaBoissiere and Frederic
Robidoux and the staff of the McGill University and Genome Quebec
Innovation Centre, Sune F. Nielsen, Borge G. Nordestgaard, and the staff
of the Copenhagen DNA laboratory, and Julie M. Cunningham, Sharon A.
Windebank, Christopher A. Hilker, Jeffrey Meyer and the staff of Mayo
Clinic Genotyping Core Facility. ABCFS wishes to thank Maggie Angelakos,
Judi Maskiell and Gillian Dite. ABCS wishes to thank Sten Cornelissen,
Richard van Hien, Linde Braaf, Frans Hogervorst, Senno Verhoef, Laura
van t Veer, Emiel Rutgers, C Ellen van der Schoot and Femke Atsma. ABCTB
wishes to thank Christine Clarke, Rosemary Balleine, Robert Baxter,
Stephen Braye, Jane Carpenter, Jane Dahlstrom, John Forbes, Soon Lee,
Debbie Marsh, Adrienne Morey, Nirmala Pathmanathan, Rodney Scott, Allan
Spigelman, Nicholas Wilcken and Desmond Yip. Samples are made available
to researchers on a non-exclusive basis. The ACP study wishes to thank
the participants in the Thai Breast Cancer study. Special thanks also go
to the Thai Ministry of Public Health (MOPH), doctors and nurses who
helped with the data collection process. Finally, the ACP study would
like to thank Dr. Prat Boonyawongviroj, the former Permanent Secretary
of MOPH and Dr. Pornthep Siriwanarungsan, the Department
Director-General of Disease Control who have supported the study
throughout. BBCS wishes to thank Eileen Williams, Elaine Ryder-Mills and
Kara Sargus. BIGGS wishes to thank Niall McInerney, Gabrielle Colleran,
Andrew Rowan and Angela Jones. BOCS wishes to thank The Wellcome Trust
Case Control Consortium (see the WTCCC website for a full list of
contributing investigators). BSUCH wishes to thank Peter Bugert and
Medical Faculty Mannheim. CGPS wishes to thank staff and participants of
the Copenhagen General Population Study, and Dorthe Uldall Andersen,
Maria Birna Arnadottir, Anne Bank and Dorthe Kjeldgard Hansenor for the
excellent technical assistance. CNIO-BCS thanks Guillermo Pita, Charo
Alonso, Daniel Herrero, Nuria Alvarez, Pilar Zamora, Primitiva Menendez
and the Human Genotyping-CEGEN Unit (CNIO). The CTS Steering Committee
includes Leslie Bernstein, Susan Neuhausen, James Lacey, Sophia Wang,
Huiyan Ma, Yani Lu and Jessica Clague DeHart at the Beckman Research
Institute of City of Hope, Dennis Deapen, Rich Pinder, Eunjung Lee, and
Fred Schumacher at the University of Southern California, Pam Horn-Ross,
Peggy Reynolds, Christina Clarke Dur and David Nelson at the Cancer
Prevention Institute of California, and Hoda Anton-Culver, Argyrios
Ziogas and Hannah Park at the University of California Irvine.
DIETCOMPLY thanks the patients, nurses and clinical staff involved in
the study.; The University of Westminster Against Breast Cancer Research
Unit acknowledges funding from the charity Against Breast Cancer
(Registered Charity Number 1121258). ESTHER thanks Hartwig Ziegler,
Sonja Wolf and Volker Hermann. GC-HBOC thanks Heide Hellebrand, Stefanie
Engert and GC-HBOC (Supported by Deutsche Krebshilfe). GENICA thanks Dr.
Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart,
and University of Tubingen, Germany (HB, Wing-Yee Lo, Christina
Justenhoven), German Cancer Consortium (DKTK) and German Cancer Research
Center (DKFZ) (HB), Department of Internal Medicine, Evangelische
Kliniken Bonn gGmbH, Johanniter Krankenhaus, Bonn, Germany (Yon-Dschun
Ko, Christian Baisch), Institute of Pathology, University of Bonn,
Germany (Hans-Peter Fischer), Molecular Genetics of Breast Cancer,
Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, Germany (Ute
Hamann), Institute for Prevention and Occupational Medicine of the
German Social Accident Insurance, Institute of the Ruhr University
Bochum (IPA), Bochum, Germany (TB, Beate Pesch, Sylvia Rabstein, Anne
Lotz) and Institute of Occupational Medicine and Maritime Medicine,
University Medical Center Hamburg-Eppendorf, Germany (Volker Harth).
GESBC thanks Ursula Eilber. HABCS wishes to thank Michael Bremer. HEBCS
wishes to thank Kirsimari Aaltonen, Karl von Smitten, Sofia Khan, Tuomas
Heikkinen and Irja Erkkila. HMBCS wishes to thank Peter Hillemanns, Hans
Christiansen and Johann H. Karstens. KBCP wishes to thank Eija Myohanen
and Helena Kemilainen. kConFab/AOCS wishes to thank Heather Thorne,
Eveline Niedermayr, all the kConFab research nurses and staff, the heads
and staff of the Family Cancer Clinics and the clinical follow up study
(which has received funding from the NHMRC, the National Breast Cancer
Foundation, Cancer Australia and the National Institute of Health (USA))
for their contributions to this resource, and the many families who
contribute to kConFab. LAABC thanks all the study participants and the
entire data collection team, especially Annie Fung and June Yashiki.
LMBC wishes to thank Gilian Peuteman, Dominiek Smeets, Thomas Van
Brussel and Kathleen Corthouts. MARIE wishes to thank Petra Seibold,
Dieter Flesch-Janys, Judith Heinz, Nadia Obi, Alina Vrieling, Sabine
Behrens, Ursula Eilber, Muhabbet Celik, Til Olchers and Stefan Nickels.
MBCSG wishes to thank Daniela Zaffaroni of the Fondazione IRCCS Istituto
Nazionale dei Tumori (INT), Monica Barile and Irene Feroce of the
Istituto Europeo di Oncologia (IEO) and the personnel of the Cogentech
Cancer Genetic Test Laboratory. MSKCC thanks Marina Corines and Lauren
Jacobs. MTLGEBCS would like to thank Martine Tranchant (CHU de Quebec
Research Center), Marie-France Valois, Annie Turgeon and Lea Heguy
(McGill University Health Center, Royal Victoria Hospital, McGill
University) for DNA extraction, sample management and skillful technical
assistance. J.S. is Chairholder of the Canada Research Chair in
Oncogenetics. MYBRCA wishes to thank Phuah Sze Yee, Peter Kang, Kang In
Nee, Kavitta Sivanandan, Shivaani Mariapun, Yoon Sook-Yee, Daphne Lee,
Teh Yew Ching and Nur Aishah Mohd Taib for DNA extraction and patient
recruitment. NBCS wishes to thank Dr. Kristine Kleivi, PhD (K.G. Jebsen
Centre for Breast Cancer Research, Institute of Clinical Medicine,
University of Oslo, Oslo, Norway and Department of Research, Vestre
Viken, Drammen, Norway), Dr. Lars Ottestad, MD (Department of Genetics,
Institute for Cancer Research, Oslo University Hospital
Radiumhospitalet, Oslo, Norway), Prof. Em.; Rolf Karesen, MD (Department
of Oncology, Oslo University Hospital and Faculty of Medicine,
University of Oslo, Oslo, Norway), Dr. Anita Langerod, PhD (Department
of Genetics, Institute for Cancer Research, Oslo University Hospital
Radiumhospitalet, Oslo, Norway), Dr. Ellen Schlichting, MD (Department
for Breast and Endocrine Surgery, Oslo University Hospital Ullevaal,
Oslo, Norway), Dr. Marit Muri Holmen, MD (Department of Radiology and
Nuclear Medicine, Oslo University Hospital, Oslo, Norway), Prof. Toril
Sauer, MD (Department of Pathology at Akershus University hospital,
Lorenskog, Norway), Dr. Vilde Haakensen, MD (Department of Genetics,
Institute for Cancer Research, Oslo University Hospital
Radiumhospitalet, Oslo, Norway), Dr. Olav Engebraten, MD (Institute for
Clinical Medicine, Faculty of Medicine, University of Oslo and
Department of Oncology, Oslo University Hospital, Oslo, Norway), Prof.
Bjorn Naume, MD (Division of Cancer Medicine and Radiotherapy,
Department of Oncology, Oslo University Hospital Radiumhospitalet, Oslo,
Norway), Dr. Cecile E. Kiserud, MD (National Advisory Unit on Late
Effects after Cancer Treatment, Department of Oncology, Oslo University
Hospital, Oslo, Norway and Department of Oncology, Oslo University
Hospital, Oslo, Norway), Dr. Kristin V. Reinertsen, MD (National
Advisory Unit on Late Effects after Cancer Treatment, Department of
Oncology, Oslo University Hospital, Oslo, Norway and Department of
Oncology, Oslo University Hospital, Oslo, Norway), Assoc. Prof. Aslaug
Helland, MD (Department of Genetics, Institute for Cancer Research and
Department of Oncology, Oslo University Hospital Radiumhospitalet, Oslo,
Norway), Dr. Margit Riis, MD (Dept of Breast- and Endocrine Surgery,
Oslo University Hospital, Ulleval, Oslo, Norway), Dr. Ida Bukholm, MD
(Department of Breast-Endocrine Surgery, Akershus University Hospital,
Oslo, Norway and Department of Oncology, Division of Cancer Medicine,
Surgery and Transplantation, Oslo University Hospital, Oslo, Norway),
Prof. Per Eystein Lonning, MD (Section of Oncology, Institute of
Medicine, University of Bergen and Department of Oncology, Haukeland
University Hospital, Bergen, Norway), and Grethe I. Grenaker Alnaes,
M.Sc. (Department of Genetics, Institute for Cancer Research, Oslo
University Hospital Radiumhospitalet, Oslo, Norway). NBHS wishes to
thank study participants and research staff for their contributions and
commitment to this study. OBCS thanks Meeri Otsukka and Kari Mononen.
OFBCR wishes to thank Teresa Selander and Nayana Weerasooriya. ORIGO
wishes to thank E. Krol-Warmerdam and J. Blom for patient accrual,
administering questionnaires and managing clinical information. The LUMC
survival data were retrieved from the Leiden hospital-based cancer
registry system (ONCDOC) with the help of Dr. J. Molenaar. PBCS wishes
to thank Louise Brinton, Mark Sherman, Neonila Szeszenia-Dabrowska,
Beata Peplonska, Witold Zatonski, Pei Chao and Michael Stagner. pKARMA
wishes to thank the Swedish Medical Research Counsel. RBCS wishes to
thank Petra Bos, Jannet Blom, Ellen Crepin, Elisabeth Huijskens, Annette
Heemskerk and the Erasmus MC Family Cancer Clinic. SASBAC thanks the
Swedish Medical Research Counsel. SBCGS wishes to thank the study
participants and research staff for their contributions and commitment
to this study. SBCS wishes to thank Sue Higham, Helen Cramp, Ian Brock,
Sabapathy Balasubramanian and Dan Connley. SEARCH wishes to thank the
SEARCH and EPIC teams. SGBCC wishes to thank the participants and
research coordinator Kimberley Chua.; SKKDKFZS wishes to thank all study
participants, clinicians, family doctors, researchers and technicians
for their contributions and commitment to this study. TNBCC wishes to
thank Robert Pilarski and Charles Shapiro who were instrumental in the
formation of the OSU Breast Cancer Tissue Bank. We thank the Human
Genetics Sample Bank for processing of samples and providing OSU
Columbus area control samples. UCIBCS wishes to thank Irene Masunaka.
UKBGS wishes to thank Breakthrough Breast Cancer and the Institute of
Cancer Research for support and funding of the Breakthrough Generations
Study, and the study participants, study staff, and the doctors, nurses
and other health care providers and health information sources who have
contributed to the study. We acknowledge NHS funding to the Royal
Marsden/ICR NIHR Biomedical Research Centre.; CIMBA studies acknowledge
the following. BCFR-AU wishes to thank Maggie Angelakos, Judi Maskiell,
Gillian Dite and Helen Tsimiklis. BCFR-NY wishes to thank members and
participants in the New York site of the Breast Cancer Family Registry
for their contributions to the study. BCFR-ON wishes to thank members
and participants in the Ontario Familial Breast Cancer Registry for
their contributions to the study. BFBOCC-LT acknowledges Vilius
Rudaitis, Laimonas Griskevicius, Ramunas Janavicius. BFBOCC-LV
acknowledges Drs. Janis Eglitis, Anna Krilova and Aivars Stengrevics.
BMBSA wishes to thank the families who contribute to the BMBSA study.
BRICOH wishes to thank Yuan Chun Ding and Linda Steele for their work in
participant enrollment and biospecimen and data management. CNIO wishes
to thank Alicia Barroso, Rosario Alonso and Guillermo Pita for their
assistance. The CONSIT TEAM wishes to thank Maria Grazia Tibiletti of
the Ospedale di Circolo-Universitu dellInsubria,Varese, Italy, Giulietta
Scuvera of the Fondazione IRCCS Istituto Nazionale Tumori (INT), Milan,
Gabriele Capone of the University of Florence, Florence, Italy,
Alessandra Viel and Riccardo Dolcetti of the CRO Aviano National Cancer
Institute, Aviano, Italy, Aline Martayan of the Istituto Nazionale
Tumori Regina Elena, Rome, Italy, Stefania Tommasi e Brunella Pilato of
the Istituto Nazionale Tumori "Giovanni Paolo II", Bari, Italy, Liliana
Varesco of the IRCCS, AOU San Martino - IST Istituto Nazionale per la
Ricerca sul Cancro, Genoa, Italy, Laura Cortesi of the University of
Modena and Reggio Emilia, Modena, Italy and Laura Ottini of the
University La Sapienza, Rome, Italy. FCCC thanks Ms. JoEllen Weaver and
Dr. Betsy Bove for their technical support. Genetic Modifiers of Cancer
Risk in BRCA1/2 Mutation Carriers (GEMO) study: National Cancer Genetics
Network (UNICANCER Genetic Group), France. We wish to thank all the GEMO
collaborating groups for their contribution to this study. GEMO
Collaborating Centers are: Coordinating Centres, Unite Mixte de
Genetique Constitutionnelle des Cancers Frequents, Hospices Civils de
Lyon - Centre Leon Berard & Equipe, Genetique du cancer du sein, Centre
de Recherche en Cancerologie de Lyon: Olga Sinilnikova dagger, Sylvie
Mazoyer, Francesca Damiola, Laure Barjhoux, Carole Verny-Pierre, Melanie
Leone, Nadia Boutry-Kryza, Alain Calender, Sophie Giraud; and Service de
Genetique Oncologique, Institut Curie, Paris: Dominique Stoppa-Lyonnet,
Marion Gauthier-Villars, Bruno Buecher, Claude Houdayer, Etienne
Rouleau, Lisa Golmard, Agnes Collet, Virginie Moncoutier, Cedrick Lefol,
Muriel Belotti, Antoine de Pauw, Camille Elan, Catherine Nogues,
Emmanuelle Fourme, Anne-Marie Birot. Institut Gustave Roussy, Villejuif:
Brigitte Bressac-de-Paillerets, Olivier Caron, Marine Guillaud-Bataille.
Centre Jean Perrin, Clermont-Ferrand: Yves-Jean Bignon, Nancy Uhrhammer.
Centre Leon Berard, Lyon: Christine Lasset, Valerie Bonadona, Sandrine
Handallou. Centre Francois Baclesse, Caen: Agnes Hardouin, Pascaline
Berthet, Dominique Vaur, Laurent Castera. Institut Paoli Calmettes,
Marseille: Hagay Sobol, Violaine Bourdon, Tetsuro Noguchi, Audrey
Remenieras, Francois Eisinger. CHU Arnaud-de-Villeneuve, Montpellier:
Isabelle Coupier, Pascal Pujol. Centre Oscar Lambret, Lille:
Jean-Philippe Peyrat, Joelle Fournier, Francoise Revillion, Philippe
Vennin dagger, Claude Adenis. Centre Paul Strauss, Strasbourg: Daniele
Muller, Jean-Pierre Fricker. Institut Bergonie, Bordeaux: Emmanuelle
Barouk-Simonet, Francoise Bonnet, Virginie Bubien, Nicolas Sevenet,
Michel Longy.; Institut Claudius Regaud, Toulouse: Christine Toulas,
Rosine Guimbaud, Laurence Gladieff, Viviane Feillel. CHU Grenoble:
Dominique Leroux, Helene Dreyfus, Christine Rebischung, Magalie
Peysselon. CHU Dijon: Fanny Coron, Laurence Faivre. CHU St-Etienne:
Fabienne Prieur, Marine Lebrun, Caroline Kientz. Hotel Dieu Centre
Hospitalier, Chambery: Sandra Fert Ferrer. Centre Antoine Lacassagne,
Nice: Marc Frenay. CHU Limoges: Laurence Venat-Bouvet. CHU Nantes:
Capucine Delnatte. CHU Bretonneau, Tours: Isabelle Mortemousque. Groupe
Hospitalier Pitie-Salpetriere, Paris: Florence Coulet, Chrystelle Colas,
Florent Soubrier, Mathilde Warcoin. CHU Vandoeuvre-les-Nancy: Johanna
Sokolowska, Myriam Bronner. CHU Besancon: Marie-Agnes Collonge-Rame,
Alexandre Damette. Creighton University, Omaha, USA: Henry T. Lynch,
Carrie L. Snyder. G-FAST wishes to thank the technical support of Ilse
Coene en Brecht Crombez. GOG: this study was supported by National
Cancer Institute grants to the Gynecologic Oncology Group (GOG)
Administrative Office and Tissue Bank (CA 27469), the GOG Statistical
and Data Center (CA 37517), and the GOG Cancer Prevention and Control
Committee (CA 101165). Drs. Greene, Mai and Savage were supported by
funding from the Intramural Research Program, NCI. HCSC was supported by
a grant RD12/00369/0006 and 12/00539 from ISCIII (Spain), partially
supported by European Regional Development FEDER funds. We acknowledge
Alicia Tosar for her technical assistance. HCSC wishes to thank the
technical support of Ilse Coene en Brecht Crombez. HEBCS would like to
thank Dr. Kristiina Aittomaki, Taru A. Muranen, Drs. Carl Blomqvist and
Kirsimari Aaltonen and RNs Irja Erkkila and Virpi Palola for their help
with the HEBCS data and samples. The Hereditary Breast and Ovarian
Cancer Research Group Netherlands (HEBON) consists of the following
Collaborating Centers: Coordinating center: Netherlands Cancer
Institute, Amsterdam, NL: M.A. Rookus, F.B.L. Hogervorst, F.E. van
Leeuwen, S. Verhoef, M.K. Schmidt, N.S. Russell, J.L. de Lange, R.
Wijnands; Erasmus Medical Center, Rotterdam, NL: J.M. Collee, A.M.W. van
den Ouweland, M.J. Hooning, C. Seynaeve, C.H.M. van Deurzen, I.M.
Obdeijn; Leiden University Medical Center, NL: C.J. van Asperen, J.T.
Wijnen, R.A.E.M. Tollenaar, P. Devilee, T.C.T.E.F. van Cronenburg;
Radboud University Nijmegen Medical Center, NL: C.M. Kets, A.R.
Mensenkamp; University Medical Center Utrecht, NL: M.G.E.M. Ausems, R.B.
van der Luijt, C.C. van der Pol; Amsterdam Medical Center, NL: C.M.
Aalfs, T.A.M. van Os; VU University Medical Center, Amsterdam, NL:
J.J.P. Gille, Q. Waisfisz, H.E.J. Meijers-Heijboer; University Hospital
Maastricht, NL: E.B. Gomez-Garcia, M.J. Blok; University Medical Center
Groningen, NL: J.C. Oosterwijk, A.H. van der Hout, M.J. Mourits, G.H. de
Bock; The Netherlands Foundation for the detection of hereditary
tumours, Leiden, NL: H.F. Vasen; The Netherlands Comprehensive Cancer
Organization (IKNL): S. Siesling, J.Verloop; The Dutch Pathology
Registry (PALGA): L.I.H. Overbeek. The HEBON study is supported by the
Dutch Cancer Society grants NKI1998-1854, NKI2004-3088, NKI2007-3756,
the Netherlands Organization of Scientific Research grant NWO 91109024,
the Pink Ribbon grants 110005 and 2014-187.WO76, the BBMRI grant NWO
184.021.007/CP46 and the Transcan grant JTC 2012 Cancer 12-054. HEBON
thanks the registration teams of IKNL and PALGA for part of the data
collection. HRBCP wishes to thank Hong Kong Sanatoriuma and Hospital for
their continual support.; HUNBOCS wishes to thank the Hungarian Breast
and Ovarian Cancer Study Group members (Janos Papp, Tibor Vaszko, Aniko
Bozsik, Timea Pocza, Judit Franko, Maria Balogh, Gabriella Domokos and
Judit Ferenczi, Department of Molecular Genetics, National Institute of
Oncology, Budapest, Hungary) and the clinicians and patients for their
contributions to this study. HVH wishes to thank the Oncogenetics Group
(VHIO), and the High Risk and Cancer Prevention Unit of the University
Hospital Vall dHebron. ICO wishes to thank the ICO Hereditary Cancer
Program team led by Dr. Gabriel Capella. INHERIT would like to thank Dr.
Martine Dumont, Martine Tranchant for sample management and skillful
technical assistance. J.S. is Chairholder of the Canada Research Chair
in Oncogenetics. J.S. and P.S. were part of the QC and Genotyping
coordinating group of iCOGS
(http://ccge.medschl.cam.ac.uk/research/consortia/icogs/) (BCAC and
CIMBA). IPOBCS wishes to thank Drs. Ana Peixoto, Catarina Santos,
Patricia Rocha and Pedro Pinto for their skillful contribution to the
study. KCONFAB wishes to thank Heather Thorne, Eveline Niedermayr, all
the kConFab research nurses and staff, the heads and staff of the Family
Cancer Clinics, and the clinical follow up study (which has received
funding from the NHMRC, the National Breast Cancer Foundation, Cancer
Australia, and the National Institute of Health (USA)) for their
contributions to this resource, and the many families who contribute to
kConFab. The Modifier Study of Quantitative Effects on Disease
(MODSQUAD) acknowledges ModSQuaD members Csilla Szabo (National Human
Genome Research Institute, National Institutes of Health, Bethesda, MD,
USA); Lenka Foretova and Eva Machackova (Department of Cancer
Epidemiology and Genetics, Masaryk Memorial Cancer Institute and MF MU,
Brno, Czech Republic) and Michal Zikan, Petr Pohlreich and Zdenek Kleibl
(Oncogynecologic Center and Department of Biochemistry and Experimental
Oncology, First Faculty of Medicine, Charles University, Prague, Czech
Republic). MSKCC wishes to thank Anne Lincoln and Lauren Jacobs. NICCC
wishes to thank the NICCC National Familial Cancer Consultation Service
team led by Sara Dishon, the laboratory team led by Dr. Flavio
Lejbkowicz, and the research field operations team led by Dr. Mila
Pinchev. NRG Oncology thanks the investigators of the Australia New
Zealand NRG Oncology group. OCGN wishes to thank members and
participants in the Ontario Cancer Genetics Network for their
contributions to the study. SEABASS would like to thank Yip Cheng Har,
Nur Aishah Mohd Taib, Phuah Sze Yee, Norhashimah Hassan and all the
research nurses, research assistants and doctors involved in the MyBrCa
Study for assistance in patient recruitment, data collection and sample
preparation. In addition, we thank Philip Iau, Sng Jen-Hwei and Sharifah
Nor Akmal for contributing samples from the Singapore Breast Cancer
Study and the HUKM-HKL study respectively. The Malaysian Breast Cancer
Genetic Study is funded by research grants from the Malaysian Ministry
of Science, Technology and Innovation, Ministry of Higher Education
(UM.C/HIR/MOHE/06) and charitable funding from the Cancer Research
Initiatives Foundation. The SMC team wishes to acknowledge the
assistance of the Meirav Comprehensive breast cancer center team at the
Sheba Medical Center for assistance in this study.; Swedish scientists
participating as SWE-BRCA collaborators are: Ake Borg, Hakan Olsson,
Helena Jernstrom, Karin Henriksson, Katja Harbst, Maria Soller and Ulf
Kristoffersson from Lund University and University Hospital; Anna
Ofverholm, Margareta Nordling, Per Karlsson and Zakaria Einbeigi from
Gothenburg Sahlgrenska University Hospital; Anna von Wachenfeldt,
Annelie Liljegren, Annika Lindblom, Brita Arver, Gisela Barbany Bustinza
and Johanna Rantala from Stockholm and Karolinska University Hospital;
Beatrice Melin, Christina Edwinsdotter Ardnor and Monica Emanuelsson
from Umea University Hospital; Hans Ehrencrona, Maritta Hellstrom Pigg
and Richard Rosenquist from Uppsala University; and Marie
Stenmark-Askmalm and Sigrun Liedgren from Linkoping University Hospital.
UCHICAGO wishes to thank Cecilia Zvocec, Qun Niu, the physicians,
genetic counselors, research nurses and staff of the Cancer Risk Clinic
for their contributions to this resource and the many families who
contribute to our program. UCLA thanks Joyce Seldon, MSGC and Lorna
Kwan, MPH, for assembling the data for this study. UCSF would like to
thank Dr. Robert Nussbaum and the following genetic counselors for
participant recruitment: Beth Crawford, Kate Loranger, Julie Mak, Nicola
Stewart, Robin Lee, Amie Blanco and Peggy Conrad, and Ms. Salina Chan
for data management. UKFOCR thanks Paul Pharoah, Simon Gayther, Susan
Ramus, Carole Pye, Patricia Harrington and Eva Wozniak for their
contributions towards the UKFOCR. UPENN wishes to thank the Breast
Cancer Research Foundation, Susan G. Komen Foundation for the cure and
Basser Research Center for BRCA. VFCTG wishes to thank Geoffrey
Lindeman, Marion Harris and Martin Delatycki of the Victorian Familial
Cancer Trials Group. VFCTG also thanks Sarah Sawyer and Rebecca Driessen
for assembling these data and Ella Thompson for performing all DNA
amplification. Funding was as follows: the work conducted for this
project at Vanderbilt Epidemiology Center is supported in part by NIH
grant R37CA070867 and endowment funds for the Ingram Professorship and
Anne Potter Wilson Chair. BCAC is funded by Cancer Research UK
(C1287/A10118, C1287/A12014) and by the European Community Seventh
Framework Programme under grant agreement number 223175
(HEALTH-F2-2009-223175) (COGS). Funding for the iCOGS infrastructure
came from the European Community Seventh Framework Programme under grant
agreement number 223175 (HEALTH-F2-2009-223175) (COGS), Cancer Research
UK (C1287/A10118, C1287/A 10710, C12292/A11174, C1281/A12014,
C5047/A8384, C5047/A15007, C5047/A10692, C8197/A16565), the National
Institutes of Health (CA128978) and Post-Cancer GWAS initiative (1U19
CA148537, 1U19 CA148065 and 1U19 CA14811he GAME-ON initiative), the
Department of Defence (W81XWH-10-1-0341), the Canadian Institutes of
Health Research (CIHR) for the CIHR Team in Familial Risks of Breast
Cancer, Komen Foundation for the Cure, the Breast Cancer Research
Foundation, and the Ovarian Cancer Research Fund. The Australian Breast
Cancer Family Study (ABCFS) was supported by grant UM1 CA164920 from the
National Cancer Institute (USA). The content of this manuscript does not
necessarily reflect the views or policies of the National Cancer
Institute or any of the collaborating centers in the Breast Cancer
Family Registry (BCFR), nor does mention of trade names, commercial
products, or organizations imply endorsement by the USA Government or
the BCFR.; The ABCFS was also supported by the National Health and
Medical Research Council of Australia, the New South Wales Cancer
Council, the Victorian Health Promotion Foundation (Australia) and the
Victorian Breast Cancer Research Consortium. J.L.H. is a National Health
and Medical Research Council (NHMRC) Australia Fellow and a Victorian
Breast Cancer Research Consortium Group Leader. M.C.S. is a NHMRC Senior
Research Fellow and a Victorian Breast Cancer Research Consortium Group
Leader. The ABCS study was supported by the Dutch Cancer Society (grants
NKI 2007-3839; 2009 4363); BBMRI-NL, which is a research infrastructure
financed by the Dutch government (NWO 184.021.007); and the Dutch
National Genomics Initiative. The Australian Breast Cancer Tissue Bank
is generously supported by the National Health and Medical Research
Council of Australia, The Cancer Institute NSW and the National Breast
Cancer Foundation. The ACP study is funded by the Breast Cancer Research
Trust, UK. The work of the BBCC was partly funded by ELAN-Fond of the
University Hospital of Erlangen. The BBCS is funded by Cancer Research
UK and Breakthrough Breast Cancer and acknowledges NHS funding to the
NIHR Biomedical Research Centre, and the National Cancer Research
Network (NCRN). ES is supported by NIHR Comprehensive Biomedical
Research Centre, Guys & St. Thomas NHS Foundation Trust in partnership
with Kings College London, UK. IT is supported by the Oxford Biomedical
Research Centre. BOCS is supported by funds from Cancer Research UK
(C8620/A8372 and C8620/A8857), a US Military Acquisition (ACQ) Activity,
Era of Hope Award (W81XWH-05-1-0204) and the Institute of Cancer
Research (UK). C.T. is funded by a Medical Research Council (UK)
Clinical Research Fellowship. BOCS acknowledges NHS funding to the Royal
Marsden/Institute of Cancer Research NIHR Specialist Cancer Biomedical
Research Centre. The BSUCH study was supported by the Dietmar-Hopp
Foundation, the Helmholtz Society and the German Cancer Research Center
(DKFZ). The CECILE study was funded by Fondation de France, Institut
National du Cancer (INCa), Ligue Nationale contre le Cancer, Ligue
contre le Cancer Grand Ouest, Agence Nationale de Securite Sanitaire
(ANSES) and Agence Nationale de la Recherche (ANR). The CGPS was
supported by the Chief Physician Johan Boserup and Lise Boserup Fund,
the Danish Medical Research Council and Herlev Hospital. The CNIO-BCS
was supported by the Instituto de Salud Carlos III, the Red Tematica de
Investigacion Cooperativa en Cancer and grants from the Asociacion
Espanola Contra el Cancer and the Fondo de Investigacion Sanitario
(PI11/00923 and PI12/00070). The CTS was initially supported by the
California Breast Cancer Act of 1993 and the California Breast Cancer
Research Fund (contract 97-10500) and is currently funded through the
National Institutes of Health (R01 CA77398). Collection of cancer
incidence data was supported by the California Department of Public
Health as part of the statewide cancer reporting program mandated by
California Health and Safety Code Section 103885. HAC receives support
from the Lon V Smith Foundation (LVS39420). The University of
Westminster curates the DietCompLyf database created by and funded by
Against Breast Cancer Registered Charity No. 1121258. The ESTHER study
was supported by a grant from the Baden Wurttemberg Ministry of Science,
Research and Arts. Additional cases were recruited in the context of the
VERDI study, which was supported by a grant from the German Cancer Aid
(Deutsche Krebshilfe).; The GC-HBOC was supported by Deutsche Krebshilfe
(107 352). The GENICA was funded by the Federal Ministry of Education
and Research (BMBF) Germany grants 01KW9975/5, 01KW9976/8, 01KW9977/0
and 01KW0114, the Robert Bosch Foundation, Stuttgart, Deutsches
Krebsforschungszentrum (DKFZ), Heidelberg, the Institute for Prevention
and Occupational Medicine of the German Social Accident Insurance,
Institute of the Ruhr University Bochum (IPA), Bochum, and the
Department of Internal Medicine, Evangelische Kliniken Bonn gGmbH, and
Johanniter Krankenhaus, Bonn, Germany. The GESBC was supported by the
Deutsche Krebshilfe e. V. [70492] and the German Cancer Research Center
(DKFZ). The HABCS study was supported by an intramural grant from
Hannover Medical School. The HEBCS was financially supported by the
Helsinki University Central Hospital Research Fund, Academy of Finland
(266528), the Finnish Cancer Society, The Nordic Cancer Union and the
Sigrid Juselius Foundation. The HERPACC was supported by a Grant-in-Aid
for Scientific Research on Priority Areas from the Ministry of
Education, Science, Sports, Culture and Technology of Japan, by a
Grant-in-Aid for the Third Term Comprehensive 10-Year Strategy for
Cancer Control from Ministry of Health, Labor and Welfare of Japan, by
Health and Labor Sciences Research Grants for Research on Applying
Health Technology from the Ministry Health, Labor and Welfare of Japan,
National Cancer Center Research and Development Fund and Grant form
Takeda Health Foundation. The HMBCS was supported by a grant from the
Friends of Hannover Medical School and by the Rudolf Bartling
Foundation. The HUBCS was supported by a grant from the German Federal
Ministry of Research and Education (RUS08/017). Financial support for
KARBAC was provided through the regional agreement on medical training
and clinical research (ALF) between Stockholm County Council and
Karolinska Institutet, the Swedish Cancer Society, The Gustav V Jubilee
foundation and and Bert von Kantzows foundation. The KBCP was
financially supported by the special Government Funding (EVO) of Kuopio
University Hospital grants, Cancer Fund of North Savo, the Finnish
Cancer Organizations and strategic funding of the University of Eastern
Finland. kConFab is supported by a grant from the National Breast Cancer
Foundation, and previously by the National Health and Medical Research
Council (NHMRC), the Queensland Cancer Fund, the Cancer Councils of New
South Wales, Victoria, Tasmania and South Australia, and the Cancer
Foundation of Western Australia. Financial support for the AOCS was
provided by the United States Army Medical Research and Materiel Command
(DAMD17-01-1-0729), Cancer Council Victoria, Queensland Cancer Fund,
Cancer Council New South Wales, Cancer Council South Australia, The
Cancer Foundation of Western Australia, Cancer Council Tasmania and the
National Health and Medical Research Council of Australia (NHMRC;
400413, 400281, 199600). G.C.T. and P.W. are supported by the NHMRC. RB
was a Cancer Institute NSW Clinical Research Fellow. LAABC is supported
by grants (1RB-0287, 3 PB-0102, 5 PB-0018, 10 PB-0098) from the
California Breast Cancer Research Program. Incident breast cancer cases
were collected by the USC Cancer Surveillance Program (CSP) which is
supported under subcontract by the California Department of Health. The
CSP is also part of the National Cancer Institute Division of Cancer
Prevention and Control Surveillance, Epidemiology, and End Results
Program, under contract number N01CN25403.; LMBC is supported by the
Stichting tegen Kanker (232-2008 and 196-2010). Diether Lambrechts is
supported by the FWO and the KULPFV/10/016-SymBioSysII. The MARIE study
was supported by the Deutsche Krebshilfe e.V. (70-2892-BR I, 106332,
108253, 108419), the Hamburg Cancer Society, the German Cancer Research
Center (DKFZ) and the Federal Ministry of Education and Research (BMBF)
Germany (01KH0402). MBCSG is supported by grants from the Italian
Association for Cancer Research (AIRC) and by funds from the Italian
citizens who allocated the 5/1000 share of their tax payment in support
of the Fondazione IRCCS Istituto Nazionale Tumori, according to Italian
laws (INT-Institutional strategic projects "5x1000"). The MCBCS was
supported by the NIH grants CA128978, CA116167, CA176785 an NIH
Specialized Program of Research Excellence (SPORE) in Breast Cancer
[CA116201], and the Breast Cancer Research Foundation and a generous
gift from the David F. and Margaret T. Grohne Family Foundation and the
Ting Tsung and Wei Fong Chao Foundation. MCCS cohort recruitment was
funded by VicHealth and Cancer Council Victoria. The MCCS was further
supported by Australian NHMRC grants 209057, 251553 and 504711 and by
infrastructure provided by Cancer Council Victoria. Cases and their
vital status were ascertained through the Victorian Cancer Registry
(VCR). The MEC was supported by NIH grants CA63464, CA54281, CA098758
and CA132839. MSKCC is supported by grants from the Breast Cancer
Research Foundation and Robert and Kate Niehaus Clinical Cancer Genetics
Initiative. The work of MTLGEBCS was supported by the Quebec Breast
Cancer Foundation, the Canadian Institutes of Health Research for the
CIHR Team in Familial Risks of Breast Cancer program, grant number
CRN-87521 and the Ministry of Economic Development, Innovation and
Export Trade, grant number PSR-SIIRI-701. MYBRCA is funded by research
grants from the Malaysian Ministry of Science, Technology and Innovation
(MOSTI), Malaysian Ministry of Higher Education (UM.C/HlR/MOHE/06) and
Cancer Research Initiatives Foundation (CARIF). Additional controls were
recruited by the Singapore Eye Research Institute, which was supported
by a grant from the Biomedical Research Council (BMRC08/1/35/19/550),
Singapore and the National medical Research Council, Singapore
(NMRC/CG/SERI/2010). The NBCS has received funding from the K.G. Jebsen
Centre for Breast Cancer Research, the Research Council of Norway grant
193387/V50 (to A-L Borresen-Dale and V.N. Kristensen) and grant
193387/H10 (to A-L Borresen-Dale and V.N. Kristensen), South Eastern
Norway Health Authority (grant 39346 to A-L Borresen-Dale) and the
Norwegian Cancer Society (to A-L Borresen-Dale and V.N. Kristensen). The
NBHS was supported by NIH grant R01CA100374. Biological sample
preparation was conducted using the Survey and Biospecimen Shared
Resource, which is supported by P30 CA68485. The Northern California
Breast Cancer Family Registry (NC-BCFR) was supported by grant UM1
CA164920 from the National Cancer Institute (USA). The content of this
manuscript does not necessarily reflect the views or policies of the
National Cancer Institute or any of the collaborating centres in the
Breast Cancer Family Registry (BCFR), nor does mention of trade names,
commercial products, or organizations imply endorsement by the USA
Government or the BCFR. The NHS was funded by NIH grant CA87969.; The
OBCS was supported by research grants from the Finnish Cancer
Foundation, the Academy of Finland (grant number 250083, 122715 and
Center of Excellence grant number 251314), the Finnish Cancer
Foundation, the Sigrid Juselius Foundation, the University of Oulu, the
University of Oulu Support Foundation and the special Governmental EVO
funds for Oulu University Hospital-based research activities. The
Ontario Familial Breast Cancer Registry (OFBCR) was supported by grant
UM1 CA164920 from the National Cancer Institute (USA). The content of
this manuscript does not necessarily reflect the views or policies of
the National Cancer Institute or any of the collaborating centres in the
Breast Cancer Family Registry (BCFR), nor does mention of trade names,
commercial products, or organizations imply endorsement by the USA
Government or the BCFR. The ORIGO study was supported by the Dutch
Cancer Society (RUL 1997-1505) and the Biobanking and Biomolecular
Resources Research Infrastructure (BBMRI-NL CP16). The PBCS was funded
by Intramural Research Funds of the National Cancer Institute,
Department of Health and Human Services, USA. The pKARMA study was
supported by Marit and Hans Rausings Initiative Against Breast Cancer.
The RBCS was funded by the Dutch Cancer Society (DDHK 2004-3124, DDHK
2009-4318). The SASBAC study was supported by funding from the Agency
for Science, Technology and Research of Singapore (A*STAR), the US
National Institute of Health (NIH) and the Susan G. Komen Breast Cancer
Foundation. The SBCGS was supported primarily by NIH grants R01CA64277,
R01CA148667 and R37CA70867. Biological sample preparation was conducted
using the Survey and Biospecimen Shared Resource, which is supported by
P30 CA68485. The scientific development and funding of this project
were, in part, supported by the Genetic Associations and Mechanisms in
Oncology (GAME-ON) Network U19 CA148065. The SBCS was supported by
Yorkshire Cancer Research S295, S299, S305PA and Sheffield Experimental
Cancer Medicine Centre. The SCCS is supported by a grant from the
National Institutes of Health (R01 CA092447). Data on SCCS cancer cases
used in this publication were provided by the Alabama Statewide Cancer
Registry; Kentucky Cancer Registry, Lexington, KY; Tennessee Department
of Health, Office of Cancer Surveillance; Florida Cancer Data System;
North Carolina Central Cancer Registry, North Carolina Division of
Public Health; Georgia Comprehensive Cancer Registry; Louisiana Tumor
Registry; Mississippi Cancer Registry; South Carolina Central Cancer
Registry; Virginia Department of Health, Virginia Cancer Registry;
Arkansas Department of Health, Cancer Registry, 4815 W. Markham, Little
Rock, AR 72205. The Arkansas Central Cancer Registry is fully funded by
a grant from National Program of Cancer Registries, Centers for Disease
Control and Prevention (CDC). Data on SCCS cancer cases from Mississippi
were collected by the Mississippi Cancer Registry which participates in
the National Program of Cancer Registries (NPCR) of the Centers for
Disease Control and Prevention (CDC). The contents of this publication
are solely the responsibility of the authors and do not necessarily
represent the official views of the CDC or the Mississippi Cancer
Registry. SEARCH is funded by a programme grant from Cancer Research UK
(C490/A10124) and supported by the UK National Institute for Health
Research Biomedical Research Centre at the University of Cambridge.;
SEBCS was supported by the BRL (Basic Research Laboratory) programme
through the National Research Foundation of Korea funded by the Ministry
of Education, Science and Technology (2012-0000347). SGBCC is funded by
the NUS start-up Grant, National University Cancer Institute Singapore
(NCIS) Centre Grant and the NMRC Clinician Scientist Award. Additional
controls were recruited by the Singapore Consortium of Cohort
Studies-Multi-ethnic cohort (SCCS-MEC), which was funded by the
Biomedical Research Council, grant number 05/1/21/19/425. SKKDKFZS is
supported by the DKFZ. The SZBCS was supported by grant
PBZ_KBN_122/P05/2004. The TBCS was funded by The National Cancer
Institute Thailand. The TNBCC was supported by a Specialized Program of
Research Excellence (SPORE) in Breast Cancer (CA116201), a grant from
the Breast Cancer Research Foundation, a generous gift from the David F.
and Margaret T. Grohne Family Foundation, the Stefanie Spielman Breast
Cancer fund and the OSU Comprehensive Cancer Center, the Hellenic
Cooperative Oncology Group research grant (HR R_BG/04) and the Greek
General Secretary for Research and Technology (GSRT) Program, Research
Excellence II, the European Union (European Social Fund - ESF), and
Greek national funds through the Operational Program "Education and
Lifelong Learning" of the National Strategic Reference Framework (NSRF)
- ARISTEIA. The TWBCS is supported by the Taiwan Biobank project of the
Institute of Biomedical Sciences, Academia Sinica, Taiwan. The UCIBCS
component of this research was supported by the NIH (CA58860, CA92044)
and the Lon V Smith Foundation (LVS39420). The UKBGS is funded by
Breakthrough Breast Cancer and the Institute of Cancer Research (ICR),
London. ICR acknowledges NHS funding to the NIHR Biomedical Research
Centre. The US3SS study was supported by Massachusetts (K.M.E.,
R01CA47305), Wisconsin (P.A.N., R01 CA47147) and New Hampshire (L.T.-E.,
R01CA69664) centres, and Intramural Research Funds of the National
Cancer Institute, Department of Health and Human Services, USA. The USRT
study was funded by the Intramural Research Program of the Division of
Cancer Epidemiology and Genetics, National Cancer Institute, National
Institutes of Health, U.S. Department of Health and Human Services.
Support for CIMBA studies: BCFR was supported by grant UM1 CA164920 from
the National Cancer Institute. The content of this manuscript does not
necessarily reflect the views or policies of the National Cancer
Institute or any of the collaborating centers in the Breast Cancer
Family Registry (BCFR), nor does mention of trade names and commercial
products, or organizations imply endorsement by the US Government or the
BCFR. BFBOCC is partly supported by Lithuania (BFBOCC-LT), Research
Council of Lithuania grant LIG-07/2012; BIDMC is supported by the Breast
Cancer Research Foundation. BRCA-gene mutations and breast cancer in
South African women (BMBSA) was supported by grants from the Cancer
Association of South Africa (CANSA) to Elizabeth J. van Rensburg; SLN
was partially supported by the Morris and Horowitz Families Endowed
Professorship. The CBCS was supported by the NEYE Foundation. CNIO was
partially supported by Spanish Association against Cancer (AECC08),
RTICC 06/0020/1060, FISPI08/1120, Mutua Madrilena Foundation (FMMA) and
SAF2010-20493. City of Hope Clinical Cancer Genetics Community Network
and the Hereditary Cancer Research Registry, supported in part by Award
Number RC4CA153828 (PI: J.; Weitzel) from the National Cancer Institute
and the Office of the Director, National Institutes of Health. The
content is solely the responsibility of the authors and does not
necessarily represent the official views of the National Institutes of
Health. Funds for CONSIT TEAM were from Italian citizens who allocated
the 5x1000 share of their tax payment in support of the Fondazione IRCCS
Istituto Nazionale Tumori, according to Italian laws (INT-Institutional
strategic projects 5x1000) to SM and from FiorGen Foundation for
Pharmacogenomics to LP. The CIMBA data management and data analysis were
supported by Cancer Research UK grants C12292/A11174 and C1287/A10118.
SH is supported by an NHMRC Program Grant to GCT. ACA is a Cancer
Research UK Senior Cancer Research Fellow. GCT is an NHMRC Senior
Principal Research Fellow. The DEMOKRITOS has been co-financed by the
European Union (European Social Fund - ESF) and Greek national funds
through the Operational Program "Education and Lifelong Learning" of the
National Strategic Reference Framework (NSRF) - Research Funding Program
of the General Secretariat for Research & Technology: SYN11_10_19 NBCA.
Investing in knowledge society through the European Social Fund. The
DKFZ study was supported by the DKFZ. EMBRACE is supported by Cancer
Research UK Grants C1287/A10118 and C1287/A11990. D. Gareth Evans and
Fiona Lalloo are supported by an NIHR grant to the Biomedical Research
Centre, Manchester. The Investigators at The Institute of Cancer
Research and The Royal Marsden NHS Foundation Trust are supported by an
NIHR grant to the Biomedical Research Centre at The Institute of Cancer
Research and The Royal Marsden NHS Foundation Trust. Ros Eeles and
Elizabeth Bancroft are supported by Cancer Research UK Grant
C5047/A8385. Ros Eelses is also supported by NIHR support to the
Biomedical Research Centre at The Institute of Cancer Research and The
Royal Marsden NHS Foundation Trust. FCCC was supported by The University
of Kansas Cancer Center (P30 CA168524) and the Kansas Bioscience
Authority Eminent Scholar Program. A.K.G. was funded by 5U01CA113916,
R01CA140323, and by the Chancellors Distinguished Chair in Biomedical
Sciences Professorship. The German Consortium of Hereditary Breast and
Ovarian Cancer (GC-HBOC) is supported by the German Cancer Aid (grant no
109076, Rita K. Schmutzler) and by the Center for Molecular Medicine
Cologne (CMMC). The GEMO study was supported by the Ligue Nationale
Contre le Cancer; the Association "Le cancer du sein, parlons-en!"
Award; the Canadian Institutes of Health Research for the "CIHR Team in
Familial Risks of Breast Cancer" program and the French National
Institute of Cancer (INCa). GEORGETOWN (CI) received support from the
Non-Therapeutic Subject Registry Shared Resource at Georgetown
University (NIH/NCI grant P30-CA051008), the Fisher Center for Familial
Cancer Research, and Swing For the Cure. Kim De Leeneer (the G-FAST
study) is supported by GOA grant BOF10/GOA/019 (Ghent University) and
spearhead financing of Ghent University Hospital. The HCSC was supported
by a grant RD12/00369/0006 and 12/00539 from ISCIII (Spain), partially
supported by European Regional Development FEDER funds. HEBCS was
financially supported by the Helsinki University Hospital Research Fund,
Academy of Finland (266528), the Finnish Cancer Society and the Sigrid
Juselius Foundation.; The HEBON study is supported by the Dutch Cancer
Society grants NKI1998-1854, NKI2004-3088, NKI2007-3756, the Netherlands
Organization of Scientific Research grant NWO 91109024, the Pink Ribbon
grant 110005 and the BBMRI grant NWO 184.021.007/CP46. HEBON thanks the
registration teams of the Comprehensive Cancer Centre Netherlands and
Comprehensive Centre South (together the Netherlands Cancer Registry)
and PALGA (Dutch Pathology Registry) for part of the data collection.
HRBCP is supported by The Hong Kong Hereditary Breast Cancer Family
Registry and the Dr. Ellen Li Charitable Foundation, Hong Kong. The
Hungarian Breast and Ovarian Cancer Study was supported by Hungarian
Research Grants KTIA-OTKA CK-80745, OTKA K-112228 and the Norwegian EEA
Financial Mechanism Hu0115/NA/2008-3/OP-9. ICO: contract grant sponsor,
Asociacion Espanola Contra el Cancer, Spanish Health Research Fund;
Carlos III Health Institute; Catalan Health Institute and Autonomous
Government of Catalonia. Contract grant numbers: ISCIIIRETIC
RD06/0020/1051, RD12/0036/008, PI10/01422, PI10/00748, PI13/00285,
PIE13/00022, 2009SGR290 and 2014SGR364. The IHCC was supported by Grant
PBZ_KBN_122/P05/2004. The ILUH group was supported by the Icelandic
Association "Walking for Breast Cancer Research" and by the Landspitali
University Hospital Research Fund. INHERIT was supported by the Canadian
Institutes of Health Research for the "CIHR Team in Familial Risks of
Breast Cancer" programme, the Canadian Breast Cancer Research
Alliance-grant 019511 and the Ministry of Economic Development,
Innovation and Export Trade - grant PSR-SIIRI-701. IOVHBOCS is supported
by Ministero della Salute and "5x1000" Istituto Oncologico Veneto grant.
The IPOBCS study was in part supported by Liga Portuguesa Contra o
Cancro. kConFab is supported by a grant from the National Breast Cancer
Foundation, and previously by the National Health and Medical Research
Council (NHMRC), the Queensland Cancer Fund, the Cancer Councils of New
South Wales, Victoria, Tasmania and South Australia, and the Cancer
Foundation of Western Australia. KOHBRA is supported by a grant from the
National R&D Program for Cancer Control, Ministry for Health, Welfare
and Family Affairs, Republic of Korea (1020350). MAYO is supported by
NIH grants CA116167, CA128978 and CA176785, an NCI Specialized Program
of Research Excellence (SPORE) in Breast Cancer (CA116201), a U.S.
Department of Defence Ovarian Cancer Idea award (W81XWH-10-1-0341), a
grant from the Breast Cancer Research Foundation, a generous gift from
the David F. and Margaret T. Grohne Family Foundation. Jewish General
Hospital Weekend to End Breast Cancer, Quebec Ministry of Economic
Development, Innovation and Export Trade. MODSQUAD was supported by MH
CZ - DRO (MMCI, 00209805) and by the European Regional Development Fund
and the State Budget of the Czech Republic (RECAMO,
CZ.1.05/2.1.00/03.0101) to LF, and by Charles University in Prague
project UNCE204024 (MZ). MSKCC is supported by grants from the Breast
Cancer Research Foundation, the Robert and Kate Niehaus Clinical Cancer
Genetics Initiative, and the Andrew Sabin Research Fund. NAROD was
supported by NIH grant:1R01 CA149429-01. The research of Drs. MH Greene
and PL Mai was supported by the Intramural Research Program of the US
National Cancer Institute, NIH, and by support services contracts
NO2-CP-11019-50 and N02-CP-65504 with Westat Inc, Rockville, MD. NICCC
is supported by Clalit Health Services in Israel.; Some of its
activities are supported by the Israel Cancer Association and the Breast
Cancer Research Foundation (BCRF), NY. NNPIO has been supported by the
Russian Federation for Basic Research (grants 13-04-92613, 14-04-93959
and 15-04-01744). NRG Oncology was supported by National Cancer
Institute grants to the NRG Oncology Administrative Office and Tissue
Bank (CA 27469), the NRG Oncology Statistical and Data Center (CA
37517), and NRG Oncologys Cancer Prevention and Control Committee (CA
101165). Drs. Greene, Mai and Savage were supported by funding from the
Intramural Research Program, NCI. OSUCCG is supported by the Ohio State
University Comprehensive Cancer Center. PBCS was supported by the ITT
(Istituto Toscano Tumori) grants 2011-2013. SEABASS was supported by the
Ministry of Science, Technology and Innovation, Ministry of Higher
Education (UM.C/HlR/MOHE/06) and Cancer Research Initiatives Foundation.
SMC was partially funded through a grant by the Israel cancer
association and the funding for the Israeli Inherited Breast Cancer
Consortium. SWE-BRCA collaborators are supported by the Swedish Cancer
Society. UCHICAGO is supported by NCI Specialized Program of Research
Excellence (SPORE) in Breast Cancer (CA125183), R01 CA142996,
1U01CA161032 and by the Ralph and Marion Falk Medical Research Trust,
the Entertainment Industry Fund National Womens Cancer Research Alliance
and the Breast Cancer research Foundation. OIO is an ACS Clinical
Research Professor. UCLA was supported by the Jonsson Comprehensive
Cancer Center Foundation, Breast Cancer Research Foundation. UCSF was
supported by the UCSF Cancer Risk Program and Helen Diller Family
Comprehensive Cancer Center. UKFOCR was supported by a project grant
from CRUK to Paul Pharoah. UPENN was supported by National Institutes of
Health (NIH) (R01-CA102776 and R01-CA083855; Breast Cancer Research
Foundation; Susan G. Komen Foundation for the cure, Basser Research
Center for BRCA. UPITT/MWH was supported by the Frieda G. and Saul F.
Shapira BRCA-Associated Cancer Research Program, Hackers for Hope
Pittsburgh. Kate Lawrenson is funded by Ovarian Cancer Research Fund
(OCRF) grant number 258807 and an Ann Schreiber Program of Excellence
award from the Ovarian Cancer Research Fund (POE/USC/01.12). Janet Lee
and Howard Shen are funded by National Institute of Health grant number
5 U19 CA148112-02. Tassja Spindler is funded by National Institute of
Health grant number CA173531-01. Work was performed within the USC
Norris Comprehensive Cancer Center which is supported by a Cancer Center
Support Grant (award number P30 CA014089) from the National Cancer
Institute. VFCTG was supported by the Victorian Cancer Agency, Cancer
Australia, National Breast Cancer Foundation. Dr. Karlan is funded by
the American Cancer Society Early Detection Professorship
(SIOP-06-258-01-COUN) and the National Center for Advancing
Translational Sciences (NCATS), Grant UL1TR000124.
NR 45
TC 1
Z9 1
U1 22
U2 32
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1465-542X
EI 1465-5411
J9 BREAST CANCER RES
JI Breast Cancer Res.
PD JUN 21
PY 2016
VL 18
AR 64
DI 10.1186/s13058-016-0718-0
PG 21
WC Oncology
SC Oncology
GA DR9CE
UT WOS:000380193900001
PM 27459855
ER
PT J
AU Wang, SJ
Chu, CH
Guo, MR
Jiang, LL
Nie, H
Zhang, W
Wilson, B
Yang, L
Stewart, T
Hong, JS
Zhang, J
AF Wang, Shijun
Chu, Chun-Hsien
Guo, Mingri
Jiang, Lulu
Nie, Hui
Zhang, Wei
Wilson, Belinda
Yang, Li
Stewart, Tessandra
Hong, Jau-Shyong
Zhang, Jing
TI Identification of a specific alpha-synuclein peptide (alpha-Syn 29-40)
capable of eliciting microglial superoxide production to damage
dopaminergic neurons
SO JOURNAL OF NEUROINFLAMMATION
LA English
DT Article
DE alpha-Synuclein; gp91(phox); Superoxide; Neuronal damage; Microglia
ID POINT MUTATIONS A30P; PARKINSONS-DISEASE; NADPH OXIDASE; IN-VIVO;
ACTIVATION; NEURODEGENERATION; AGGREGATION; PHOSPHORYLATION;
NEUROTOXICITY; A53T
AB Background: Misfolded alpha-synuclein (alpha-Syn) aggregates participate in the pathogenesis of synucleinopathies, such as Parkinson's disease. Whereas much is known about how the various domains within full-length alpha-Syn (FL-alpha-Syn) contribute to the formation of alpha-Syn aggregates and therefore to their neurotoxicity, little is known about whether the individual peptides that can be generated from alpha-syn, possibly as intermediate metabolites during degradation of misfolded alpha-Syn aggregates, are neurotoxic themselves.
Methods: A series of synthesized alpha-Syn peptides, corresponding to the locus in FL-alpha-Syn containing alanine 30, substitution of which with a proline causes a familial form of Parkinson's disease, were examined for their capacity of inducing release of microglial superoxide. The neurotoxicity of these peptides was measured according to their influence on the ability of neuroglial cultures deficient in gp91(phox), the catalytic unit of NADPH oxidase (Nox2), or wild-type cultures to take up 3H-labeled dopamine and on the number of tyrosine hydroxylase-staining-positive neurons. Western blots and confocal images were utilized to analyze membrane translocation of p47(phox) and p67(phox), phosphorylation of p47phox and Erk1/2 kinase, and binding of alpha-Syn peptides to gp91(phox). Activation of brain microglia in mice injected with alpha-Syn peptides was demonstrated by immunostaining for major histocompatibility complex (MHC)-II along with qPCR for Ib alpha-1 and MHC-II.
Results: We report alpha-Syn (29-40) as a specific peptide capable of activating microglial Nox2 to produce superoxide and cause dopaminergic neuronal damage. Administered to mice, this peptide also activated brain microglia to increase expression of MHC-II and Ib alpha-1 and stimulated oxidation reaction. Exploring the underlying mechanisms showed that alpha-Syn (29-40) peptide triggered Nox2 to generate extracellular superoxide and its metabolite H2O2 by binding to the catalytic unit gp91(phox) of Nox2; diffusing into cytosol, H2O2 activated Erk1/2 kinase to phosphorylate p47(phox) and p67(phox) and further activated Nox2, establishing a positive feedback loop to amplify the Nox2-mediated response.
Conclusions: Collectively, our study suggests novel information regarding how alpha-Syn causes neuronal injury, possibly including mechanisms involving abnormal metabolites of alpha -Syn aggregates.
C1 [Wang, Shijun; Chu, Chun-Hsien; Guo, Mingri; Jiang, Lulu; Nie, Hui; Wilson, Belinda; Hong, Jau-Shyong] NIEHS, Neuropharmacol Sect, Neurobiol Lab, NIH, Res Triangle Pk, NC 27709 USA.
[Wang, Shijun; Yang, Li; Stewart, Tessandra; Zhang, Jing] Univ Washington, Sch Med, Dept Pathol, Seattle, WA 98104 USA.
[Chu, Chun-Hsien] Natl Cheng Kung Univ, Inst Mol Med, Tainan 70101, Taiwan.
[Guo, Mingri] Tianjin Med Univ, Tianjin Haihe Hosp, Tianjin Inst Resp Dis, Dept Lab Med, Tianjin 300350, Peoples R China.
[Jiang, Lulu] Shandong Univ, Sch Publ Hlth, Inst Toxicol, Jinan 250012, Shandong, Peoples R China.
[Zhang, Wei] Capital Med Univ, Beijing Tiantan Hosp, Dept Geriatr, Beijing 100050, Peoples R China.
[Zhang, Jing] Peking Univ, Hlth Sci Ctr, Dept Pathol, Beijing 100083, Peoples R China.
RP Hong, JS (reprint author), NIEHS, Neuropharmacol Sect, Neurobiol Lab, NIH, Res Triangle Pk, NC 27709 USA.; Zhang, J (reprint author), Univ Washington, Sch Med, Dept Pathol, Seattle, WA 98104 USA.; Zhang, J (reprint author), Peking Univ, Hlth Sci Ctr, Dept Pathol, Beijing 100083, Peoples R China.
EM hong3@niehs.nih.gov; zhangj@uw.edu
FU NIEHS; National Institutes of Health [R01 ES019277, R01 ES016873]
FX This study was supported by the intramural funding from the NIEHS (to
JSH) and the National Institutes of Health Grants R01 ES019277 and R01
ES016873 (to JZ).
NR 46
TC 0
Z9 0
U1 4
U2 4
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1742-2094
J9 J NEUROINFLAMM
JI J. Neuroinflamm.
PD JUN 21
PY 2016
VL 13
AR 158
DI 10.1186/s12974-016-0606-7
PG 19
WC Immunology; Neurosciences
SC Immunology; Neurosciences & Neurology
GA DQ0BS
UT WOS:000378863300002
PM 27329107
ER
PT J
AU Burg, AR
Quigley, L
Jones, AV
O'Connor, GM
Boelte, K
McVicar, DW
Orr, SJ
AF Burg, Ashley R.
Quigley, Laura
Jones, Adam V.
O'Connor, Geraldine M.
Boelte, Kimberly
McVicar, Daniel W.
Orr, Selinda J.
TI Orally administered beta-glucan attenuates the Th2 response in a model
of airway hypersensitivity
SO SPRINGERPLUS
LA English
DT Article
DE beta-Glucan; Th2; Airway inflammation; Eosinophils
ID TUMOR-BEARING MICE; T-CELL RESPONSES; DENDRITIC CELLS;
MONOCLONAL-ANTIBODIES; MOUSE MODELS; ASTHMA; DECTIN-1; RECEPTOR;
DISEASE; MACROPHAGES
AB beta-Glucan is a polysaccharide that can be extracted from fungal cell walls. Wellmune WGP (R), a preparation of beta-1,3/1,6-glucans, is a dietary supplement that has immunomodulating properties. Here we investigated the effect WGP had on a mouse model of asthma. OVA-induced asthma in mice is characterized by infiltration of eosinophils into the lung, production of Th2 cytokines and IgE. Daily oral administration of WGP (400 mu g) significantly reduced the influx of eosinophils into the lungs of OVA-challenged mice compared to control mice. In addition, WGP inhibited pulmonary production of Th2 cytokines (IL-4, IL-5, IL-13), however serum IgE levels were unaffected by WGP treatment. These data indicate that WGP could potentially be useful as an oral supplement for some asthma patients, however, it would need to be combined with therapies that target other aspects of the disease such as IgE levels. As such, further studies that examine the potential of WGP in combination with other therapies should be explored.
C1 [Orr, Selinda J.] Cardiff Univ, Sch Med, Div Infect & Immun, Tenovus Bldg,Heath Pk, Cardiff CF14 4XN, S Glam, Wales.
[Burg, Ashley R.; Quigley, Laura; O'Connor, Geraldine M.; Boelte, Kimberly; McVicar, Daniel W.; Orr, Selinda J.] NCI, Canc & Inflammat Program, Frederick, MD 21702 USA.
[Burg, Ashley R.] Univ Alabama Birmingham, Dept Microbiol, Birmingham, AL 35205 USA.
[Jones, Adam V.] Cardiff & Vale Univ Hlth Board, Univ Dent Hosp, Cardiff CF14 4XY, S Glam, Wales.
[O'Connor, Geraldine M.] Univ Chester, Dept Biol Sci, Chester CH1 4BJ, Cheshire, England.
RP Orr, SJ (reprint author), Cardiff Univ, Sch Med, Div Infect & Immun, Tenovus Bldg,Heath Pk, Cardiff CF14 4XN, S Glam, Wales.; Orr, SJ (reprint author), NCI, Canc & Inflammat Program, Frederick, MD 21702 USA.
EM OrrS@cardiff.ac.uk
FU NIH Office of Dietary Supplements; Intramural Research Program of the
NIH, National Cancer Institute; Royal Society [099953/Z/12/Z]; Wellcome
Trust
FX This research was supported in part by the NIH Office of Dietary
Supplements and in part by the Intramural Research Program of the NIH,
National Cancer Institute. SJO is supported by a Sir Henry Dale
Fellowship jointly funded by the Wellcome Trust and the Royal Society
(Grant Number 099953/Z/12/Z). We would like to thank Megan Karwan, Kelli
Czarra and Grace Williams for animal care for this project.
NR 31
TC 1
Z9 1
U1 1
U2 2
PU SPRINGER INTERNATIONAL PUBLISHING AG
PI CHAM
PA GEWERBESTRASSE 11, CHAM, CH-6330, SWITZERLAND
SN 2193-1801
J9 SPRINGERPLUS
JI SpringerPlus
PD JUN 21
PY 2016
VL 5
AR 815
DI 10.1186/s40064-016-2501-1
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DP4OE
UT WOS:000378474400029
PM 27390655
ER
PT J
AU Jochems, C
Fantini, M
Fernando, RI
Kwilas, AR
Donahue, RN
Lepone, LM
Grenga, I
Kim, YS
Brechbiel, MW
Gulley, JL
Madan, RA
Heery, CR
Hodge, JW
Newton, R
Schlom, J
Tsang, KY
AF Jochems, Caroline
Fantini, Massimo
Fernando, Romaine I.
Kwilas, Anna R.
Donahue, Renee N.
Lepone, Lauren M.
Grenga, Italia
Kim, Young-Seung
Brechbiel, Martin W.
Gulley, James L.
Madan, Ravi A.
Heery, Christopher R.
Hodge, James W.
Newton, Robert
Schlom, Jeffrey
Tsang, Kwong Y.
TI The IDO1 selective inhibitor epacadostat enhances dendritic cell
immunogenicity and lytic ability of tumor antigen-specific T cells
SO ONCOTARGET
LA English
DT Article
DE IDO inhibitor; dendritic cells; T cells; indoleamine-2,3-dioxygenase
(IDO); Tregs
ID INDOLEAMINE 2,3-DIOXYGENASE EXPRESSION; HUMAN CARCINOEMBRYONIC ANTIGEN;
ARYL-HYDROCARBON RECEPTOR; DRAINING LYMPH-NODES; TRYPTOPHAN CATABOLISM;
RESISTANCE MECHANISM; NK CELLS; CANCER; IMMUNOTHERAPY; CONVERSION
AB Epacadostat is a novel inhibitor of indoleamine-2,3-dioxygenase-1 (IDO1) that suppresses systemic tryptophan catabolism and is currently being evaluated in ongoing clinical trials. We investigated the effects of epacadostat on (a) human dendritic cells (DCs) with respect to maturation and ability to activate human tumor antigen-specific cytotoxic T-cell (CTL) lines, and subsequent T-cell lysis of tumor cells, (b) human regulatory T cells (Tregs), and (c) human peripheral blood mononuclear cells (PBMCs) in vitro. Simultaneous treatment with epacadostat and IFN-gamma plus lipopolysaccharide (LPS) did not change the phenotype of matured human DCs, and as expected decreased the tryptophan breakdown and kynurenine production. Peptide-specific T-cell lines stimulated with DCs pulsed with peptide produced significantly more IFN-gamma, TNF alpha, GM-CSF and IL-8 if the DCs were treated with epacadostat. These T cells also displayed higher levels of tumor cell lysis on a per cell basis. Epacadostat also significantly decreased Treg proliferation induced by IDO production from IFN-gamma plus LPS matured human DCs, although the Treg phenotype did not change. Multicolor flow cytometry was performed on human PBMCs treated with epacadostat; analysis of 123 discrete immune cell subsets revealed no changes in major immune cell types, an increase in activated CD83(+) conventional DCs, and a decrease in immature activated Tim3(+) NK cells. These studies show for the first time several effects of epacadostat on human DCs, and subsequent effects on CTL and Tregs, and provide a rationale as to how epacadostat could potentially increase the efficacy of immunotherapeutics, including cancer vaccines.
C1 [Jochems, Caroline; Fantini, Massimo; Fernando, Romaine I.; Kwilas, Anna R.; Donahue, Renee N.; Lepone, Lauren M.; Grenga, Italia; Heery, Christopher R.; Hodge, James W.; Schlom, Jeffrey; Tsang, Kwong Y.] NCI, Lab Tumor Immunol & Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Kim, Young-Seung; Brechbiel, Martin W.] NCI, Radioimmune Inorgan Chem Sect, Radiat Oncol Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA.
[Gulley, James L.; Madan, Ravi A.] NCI, Genitourinary Malignancies Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Newton, Robert] Incyte Corp, Wilmington, DE USA.
RP Schlom, J (reprint author), NCI, Lab Tumor Immunol & Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM js141c@nih.gov
RI Gulley, James/K-4139-2016; Hodge, James/D-5518-2015;
OI Gulley, James/0000-0002-6569-2912; Hodge, James/0000-0001-5282-3154;
Fantini, Massimo/0000-0002-8164-2587
FU Intramural Research Program of the Center for Cancer Research, National
Cancer Institute, National Institutes of Health; National Cancer
Institute; Incyte Corporation
FX This research was supported by the Intramural Research Program of the
Center for Cancer Research, National Cancer Institute, National
Institutes of Health, as well as through a Cooperative Research and
Development Agreement (CRADA) between the National Cancer Institute and
Incyte Corporation.
NR 46
TC 4
Z9 4
U1 13
U2 17
PU IMPACT JOURNALS LLC
PI ALBANY
PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA
SN 1949-2553
J9 ONCOTARGET
JI Oncotarget
PD JUN 21
PY 2016
VL 7
IS 25
BP 37762
EP 37772
DI 10.18632/oncotarget.9326
PG 11
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA DP1CW
UT WOS:000378229100027
PM 27192116
ER
PT J
AU Flanders, KC
Yang, YA
Herrmann, M
Chen, JQ
Mendoza, N
Mirza, AM
Wakefield, LM
AF Flanders, Kathleen C.
Yang, Yu-an
Herrmann, Michelle
Chen, JinQiu
Mendoza, Nerissa
Mirza, Amer M.
Wakefield, Lalage M.
TI Quantitation of TGF-beta proteins in mouse tissues shows reciprocal
changes in TGF-beta 1 and TGF-beta 3 in normal vs neoplastic mammary
epithelium
SO ONCOTARGET
LA English
DT Article
DE TGF-beta isoforms; protein; quantitation; mouse tissues; mammary gland
ID TRANSFORMING-GROWTH-FACTOR; INDUCED PULMONARY-FIBROSIS; BREAST-CANCER;
IMMUNOHISTOCHEMICAL LOCALIZATION; GROWTH-FACTOR-BETA-1 GENE; EXPRESSION
PATTERNS; TRANSGENIC MICE; MESSENGER-RNA; TUMOR; DISEASE
AB Transforming growth factor-beta s (TGF-beta s) regulate tissue homeostasis, and their expression is perturbed in many diseases. The three isoforms (TGF-beta 1, -beta 2, and -beta 3) have similar bioactivities in vitro but show distinct activities in vivo. Little quantitative information exists for expression of TGF-beta isoform proteins in physiology or disease. We developed an optimized method to quantitate protein levels of the three isoforms, using a Luminex (R) xMAP (R)-based multianalyte assay following acid-ethanol extraction of tissues. Analysis of multiple tissues and plasma from four strains of adult mice showed that TGF-beta 1 is the predominant isoform with TGF-beta 2 being similar to 10-fold lower. There were no sex-specific differences in isoform expression, but some tissues showed inter-strain variation, particularly for TGF-beta 2. The only adult tissue expressing appreciable TGF-beta 3 was the mammary gland, where its levels were comparable to TGF-beta 1. In situ hybridization showed the luminal epithelium as the major source of all TGF-beta isoforms in the normal mammary gland. TGF-beta 1 protein was 3-8-fold higher in three murine mammary tumor models than in normal mammary gland, while TGF-beta 3 protein was 2-3-fold lower in tumors than normal tissue, suggesting reciprocal regulation of these isoforms in mammary tumorigenesis.
C1 [Flanders, Kathleen C.; Yang, Yu-an; Herrmann, Michelle; Chen, JinQiu; Wakefield, Lalage M.] NCI, Lab Canc Biol & Genet, Bethesda, MD 20892 USA.
[Mendoza, Nerissa; Mirza, Amer M.] Xoma Corp, Berkeley, CA 94710 USA.
RP Flanders, KC (reprint author), NCI, Lab Canc Biol & Genet, Bethesda, MD 20892 USA.
EM flanderk@mail.nih.gov
FU Intramural Research Program of the NCI, NIH [ZIA BC 010881]
FX Funding came from the Intramural Research Program of the NCI, NIH,
project ZIA BC 010881.
NR 65
TC 0
Z9 0
U1 0
U2 1
PU IMPACT JOURNALS LLC
PI ALBANY
PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA
SN 1949-2553
J9 ONCOTARGET
JI Oncotarget
PD JUN 21
PY 2016
VL 7
IS 25
BP 38164
EP 38179
DI 10.18632/oncotarget.9416
PG 16
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA DP1CW
UT WOS:000378229100060
PM 27203217
ER
PT J
AU Jiao, XD
Kabir, F
Irum, B
Khan, AO
Wang, QW
Li, D
Khan, AA
Husnain, T
Akram, J
Riazuddin, S
Hejtmancik, JF
Riazuddin, SA
AF Jiao, Xiaodong
Kabir, Firoz
Irum, Bushra
Khan, Arif O.
Wang, Qiwei
Li, David
Khan, Asma A.
Husnain, Tayyab
Akram, Javed
Riazuddin, Sheikh
Hejtmancik, J. Fielding
Riazuddin, S. Amer
TI A Common Ancestral Mutation in CRYBB3 Identified in Multiple
Consanguineous Families with Congenital Cataracts
SO PLOS ONE
LA English
DT Article
ID AUTOSOMAL RECESSIVE CATARACT; PAKISTANI FAMILIES; NONSENSE MUTATION;
LOCUS; GENE; LENS; BLINDNESS; PROTEINS; MAPS
AB Purpose
This study was performed to investigate the genetic determinants of autosomal recessive congenital cataracts in large consanguineous families.
Methods
Affected individuals underwent a detailed ophthalmological examination and slit-lamp photographs of the cataractous lenses were obtained. An aliquot of blood was collected from all participating family members and genomic DNA was extracted from white blood cells. Initially, a genome-wide scan was performed with genomic DNAs of family PKCC025 followed by exclusion analysis of our familial cohort of congenital cataracts. Protein-coding exons of CRYBB1, CRYBB2, CRYBB3, and CRYBA4 were sequenced bidirectionally. A haplotype was constructed with SNPs flanking the causal mutation for affected individuals in all four families, while the probability that the four familial cases have a common founder was estimated using EM and CHM-based algorithms. The expression of Crybb3 in the developing murine lens was investigated using TaqMan assays.
Results
The clinical and ophthalmological examinations suggested that all affected individuals had nuclear cataracts. Genome-wide linkage analysis localized the causal phenotype in family PKCC025 to chromosome 22q with statistically significant two-point logarithm of odds (LOD) scores. Subsequently, we localized three additional families, PKCC063, PKCC131, and PKCC168 to chromosome 22q. Bidirectional Sanger sequencing identified a missense variation: c.493G>C (p.Gly165Arg) in CRYBB3 that segregated with the disease phenotype in all four familial cases. This variation was not found in ethnically matched control chromosomes, the NHLBI exome variant server, or the 1000 Genomes or dbSNP databases. Interestingly, all four families harbor a unique disease haplotype that strongly suggests a common founder of the causal mutation (p<1.64E-10). We observed expression of Crybb3 in the mouse lens as early as embryonic day 15 (E15), and expression remained relatively steady throughout development.
Conclusion
Here, we report a common ancestral mutation in CRYBB3 associated with autosomal recessive congenital cataracts identified in four familial cases of Pakistani origin.
C1 [Jiao, Xiaodong; Wang, Qiwei; Li, David; Hejtmancik, J. Fielding] NEI, Ophthalm Genet & Visual Funct Branch, NIH, Bethesda, MD 20892 USA.
[Kabir, Firoz; Irum, Bushra; Riazuddin, S. Amer] Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Baltimore, MD 21287 USA.
[Irum, Bushra; Khan, Asma A.; Husnain, Tayyab; Riazuddin, Sheikh] Univ Punjab, Natl Ctr Excellence Mol Biol, Lahore 53700, Pakistan.
[Khan, Arif O.] King Khalid Eye Specialist Hosp, Riyadh 12329, Saudi Arabia.
[Akram, Javed; Riazuddin, Sheikh] Univ Hlth Sci, Allama Iqbal Med Coll, Lahore 54550, Pakistan.
[Akram, Javed; Riazuddin, Sheikh] Shaheed Zulfiqar Ali Bhutto Med Univ, Natl Ctr Genet Dis, Islamabad, Pakistan.
RP Riazuddin, SA (reprint author), Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Baltimore, MD 21287 USA.
EM riazuddin@jhmi.edu
FU National Eye Institute grant [1R01EY022714]; Knights Templar Eye
Foundation grant; King Khaled Eye Specialist Hospital-Johns Hopkins
University collaboration grant; National Academy of Sciences, Washington
DC USA; Higher Education Commission, Islamabad Pakistan
FX This study was supported in part by the National Eye Institute grant
1R01EY022714 (SAR), the Knights Templar Eye Foundation grant (SAR), King
Khaled Eye Specialist Hospital-Johns Hopkins University collaboration
grant (SAR), the National Academy of Sciences, Washington DC USA, and
the Higher Education Commission, Islamabad Pakistan.; The authors are
grateful to all members for their participation in this study. This
study was supported in part by the National Eye Institute grant
1R01EY022714 (SAR), the Knights Templar Eye Foundation grant (SAR), King
Khaled Eye Specialist Hospital-Johns Hopkins University collaboration
grant (SAR), the National Academy of Sciences, Washington DC USA, and
the Higher Education Commission, Islamabad Pakistan.
NR 36
TC 2
Z9 2
U1 1
U2 1
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUN 21
PY 2016
VL 11
IS 6
AR e0157005
DI 10.1371/journal.pone.0157005
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DP0WU
UT WOS:000378212400012
PM 27326458
ER
PT J
AU Cataisson, C
Michalowski, AM
Shibuya, K
Ryscavage, A
Klosterman, M
Wright, L
Dubois, W
Liu, F
Zhuang, A
Rodrigues, KB
Hoover, S
Dwyer, J
Simpson, MR
Merlino, G
Yuspa, SH
AF Cataisson, Christophe
Michalowski, Aleksandra M.
Shibuya, Kelly
Ryscavage, Andrew
Klosterman, Mary
Wright, Lisa
Dubois, Wendy
Liu, Fan
Zhuang, Anne
Rodrigues, Kameron B.
Hoover, Shelley
Dwyer, Jennifer
Simpson, Mark R.
Merlino, Glenn
Yuspa, Stuart H.
TI MET signaling in keratinocytes activates EGFR and initiates squamous
carcinogenesis
SO SCIENCE SIGNALING
LA English
DT Article
ID GROWTH-FACTOR RECEPTOR; KINASE-C-ALPHA; FACTOR-TRANSGENIC MICE;
HEPATOCYTE GROWTH; CELL CARCINOMA; FACTOR/SCATTER FACTOR;
SERINE-PROTEASE; SKIN TUMORS; LUNG-CANCER; INTRAEPIDERMAL INFLAMMATION
AB The receptor tyrosine kinase MET is abundant in many human squamous cell carcinomas (SCCs), but its functional significance in tumorigenesis is not clear. We found that the incidence of carcinogen-induced skin squamous tumors was substantially increased in transgenic MT-HGF (mouse metallothionein-hepatocyte growth factor) mice, which have increased abundance of the MET ligand HGF. Squamous tumors also erupted spontaneously on the skin of MT-HGF mice that were promoted by wounding or the application of 12-O-tetradecanoylphorbol 13-acetate, an activator of protein kinase C. Carcinogen-initiated tumors had Ras mutations, but spontaneous tumors did not. Cultured keratinocytes from MT-HGF mice and oncogenic RAS-transduced keratinocytes shared phenotypic and biochemical features of initiation that were dependent on autocrine activation of epidermal growth factor receptor (EGFR) through increased synthesis and release of EGFR ligands, which was mediated by the kinase SRC, the pseudoproteases iRhom1 and iRhom2, and the metallopeptidase ADAM17. Pharmacological inhibition of EGFR caused the regression of MT-HGF squamous tumors that developed spontaneously in orthografts of MT-HGF keratinocytes combined with dermal fibroblasts and implanted onto syngeneic mice. The global gene expression profile in MET-transformed keratinocytes was highly concordant with that in RAS-transformed keratinocytes, and a core RAS/MET coexpression network was activated in precancerous and cancerous human skin lesions. Tissue arrays revealed that many human skin SCCs have abundant HGF at both the transcript and protein levels. Thus, through the activation of EGFR, MET activation parallels a RAS pathway to contribute to human and mouse cutaneous cancers.
C1 [Cataisson, Christophe; Michalowski, Aleksandra M.; Shibuya, Kelly; Ryscavage, Andrew; Klosterman, Mary; Wright, Lisa; Dubois, Wendy; Liu, Fan; Zhuang, Anne; Rodrigues, Kameron B.; Hoover, Shelley; Dwyer, Jennifer; Simpson, Mark R.; Merlino, Glenn; Yuspa, Stuart H.] NCI, Lab Canc Biol & Genet, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Yuspa, SH (reprint author), NCI, Lab Canc Biol & Genet, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM yuspas@mail.nih.gov
OI Rodrigues, Kameron/0000-0002-0270-3688
FU intramural program of the Center for Cancer Research of the NCI
FX This work was funded by the intramural program of the Center for Cancer
Research of the NCI.
NR 96
TC 1
Z9 1
U1 0
U2 0
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 1945-0877
EI 1937-9145
J9 SCI SIGNAL
JI Sci. Signal.
PD JUN 21
PY 2016
VL 9
IS 433
AR ra62
DI 10.1126/scisignal.aaf5106
PG 15
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA DP2RU
UT WOS:000378339500002
PM 27330189
ER
PT J
AU Vasan, RS
Benjamin, EJ
AF Vasan, Ramachandran S.
Benjamin, Emelia J.
TI The Future of Cardiovascular Epidemiology
SO CIRCULATION
LA English
DT Article
DE cardiovascular diseases; epidemiology
ID AMERICAN-HEART-ASSOCIATION; LARGE SOCIAL NETWORK; UNITED-STATES;
PUBLIC-HEALTH; PHYSICAL-ACTIVITY; NATIONAL HEART; WORKING GROUP; HUMAN
GENOME; DISEASE; POPULATION
C1 [Vasan, Ramachandran S.; Benjamin, Emelia J.] NHLBI, Framingham, MA USA.
[Vasan, Ramachandran S.; Benjamin, Emelia J.] Boston Univ, Framingham Heart Study, Framingham, MA USA.
[Vasan, Ramachandran S.; Benjamin, Emelia J.] Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Evans Dept Med, Boston, MA 02215 USA.
[Vasan, Ramachandran S.; Benjamin, Emelia J.] Boston Univ, Sch Med, Dept Med, Prevent Med Sect, Boston, MA 02215 USA.
[Vasan, Ramachandran S.; Benjamin, Emelia J.] Boston Univ, Sch Med, Dept Med, Cardiol Sect, Boston, MA 02215 USA.
[Vasan, Ramachandran S.; Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02215 USA.
RP Vasan, RS (reprint author), Framingham Heart Dis Epidemiol Study, 73 Mt Wayte Ave,Ste 2, Framingham, MA 01702 USA.
EM vasan@bu.edu
OI Ramachandran, Vasan/0000-0001-7357-5970
FU National Heart, Lung, and Blood Institute, Framingham Heart Study
(National Heart, Lung, and Blood Institute/NIH) [N01-HC-25195,
HHSN268201500001I]; Boston University School of Medicine Evan's Scholar
Award; [1P50HL120163]
FX This work was supported by the National Heart, Lung, and Blood
Institute, Framingham Heart Study (National Heart, Lung, and Blood
Institute/NIH contracts N01-HC-25195 and HHSN268201500001I),
1P50HL120163, and the Boston University School of Medicine Evan's
Scholar Award (Dr Vasan).
NR 65
TC 0
Z9 0
U1 6
U2 11
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0009-7322
EI 1524-4539
J9 CIRCULATION
JI Circulation
PD JUN 21
PY 2016
VL 133
IS 25
BP 2626
EP 2633
DI 10.1161/CIRCULATIONAHA.116.023528
PG 8
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA DO9LT
UT WOS:000378108800006
PM 27324358
ER
PT J
AU MacRae, CA
Vasan, RS
AF MacRae, Calum A.
Vasan, Ramachandran S.
TI The Future of Genetics and Genomics Closing the Phenotype Gap in
Precision Medicine
SO CIRCULATION
LA English
DT Article
DE genetics; genomics; phenotyping
ID CONGENITAL HEART-DISEASE; MISSING HERITABILITY; HIRSCHSPRUNG-DISEASE;
ATRIAL-FIBRILLATION; WIDE ASSOCIATION; EXOME DATA; VARIANTS; RISK; LOCI;
CARDIOMYOPATHY
C1 [MacRae, Calum A.] Brigham & Womens Hosp, Div Cardiovasc, 75 Francis St, Boston, MA 02115 USA.
[MacRae, Calum A.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[MacRae, Calum A.] Broad Inst Harvard & MIT, Boston, MA USA.
[Vasan, Ramachandran S.] NHLBI, Framingham, MA USA.
[Vasan, Ramachandran S.] Boston Univ, Framingham Heart Study, Framingham, MA USA.
[Vasan, Ramachandran S.] Boston Univ, Sch Med, Evans Dept Med, Boston, MA 02215 USA.
[Vasan, Ramachandran S.] Boston Univ, Sch Med, Evans Dept Epidemiol, Boston, MA 02215 USA.
[Vasan, Ramachandran S.] Boston Univ, Sch Publ Hlth, Evans Dept Med, Boston, MA 02215 USA.
[Vasan, Ramachandran S.] Boston Univ, Sch Publ Hlth, Evans Dept Epidemiol, Boston, MA 02215 USA.
[Vasan, Ramachandran S.] Boston Univ, Sch Med, Prevent Med Sect, Boston, MA 02215 USA.
[Vasan, Ramachandran S.] Boston Univ, Sch Med, Cardiol Sect, Boston, MA 02215 USA.
RP MacRae, CA (reprint author), Brigham & Womens Hosp, Div Cardiovasc, 75 Francis St, Boston, MA 02115 USA.
EM camacrae@bics.bwh.harvard.edu
FU National Health, Lung, and Blood Institute, Framingham Heart Study
(National Health, Lung, and Blood Institute/National Institutes of
Health) [N01-HC-25195, HHSN268201500001I]; National Human Genome
Research Institute [U01 HG007690, U01 HG006500]
FX This work was supported by the National Health, Lung, and Blood
Institute, Framingham Heart Study (National Health, Lung, and Blood
Institute/National Institutes of Health contracts N01-HC-25195 and
HHSN268201500001I), and National Human Genome Research Institute (U01
HG007690, U01 HG006500).
NR 42
TC 0
Z9 0
U1 3
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0009-7322
EI 1524-4539
J9 CIRCULATION
JI Circulation
PD JUN 21
PY 2016
VL 133
IS 25
BP 2634
EP 2639
DI 10.1161/CIRCULATIONAHA.116.022547
PG 6
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA DO9LT
UT WOS:000378108800007
PM 27324359
ER
PT J
AU Kanellopoulou, C
Muljo, SA
AF Kanellopoulou, Chrysi
Muljo, Stefan A.
TI Fine-Tuning Th17 Cells: To Be or Not To Be Pathogenic?
SO IMMUNITY
LA English
DT Editorial Material
ID PROGRESSIVE HEARING-LOSS; T(H)17 CELLS; DIFFERENTIATION; INDUCTION;
MIR-96; SGK1
AB Like the story of Jekyll and Hyde, Th17 cells have two guises. One helps with host immunity, but the other can cause immunopathology. In this issue of Immunity, Dong and colleagues report that three microRNAs, miR183, miR-96, and miR-182, can enhance the pathogenicity of Th17 cells (Ichiyama et al., 2016).
C1 [Kanellopoulou, Chrysi; Muljo, Stefan A.] NIAID, Immunol Lab, NIH, Bldg 10, Bethesda, MD 20892 USA.
RP Muljo, SA (reprint author), NIAID, Immunol Lab, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM stefan.muljo@nih.gov
NR 10
TC 1
Z9 1
U1 3
U2 3
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1074-7613
EI 1097-4180
J9 IMMUNITY
JI Immunity
PD JUN 21
PY 2016
VL 44
IS 6
BP 1241
EP 1243
DI 10.1016/j.immuni.2016.06.003
PG 3
WC Immunology
SC Immunology
GA DP2SE
UT WOS:000378341200001
PM 27332724
ER
PT J
AU Voss, OH
Murakami, Y
Pena, MY
Lee, HN
Tian, LJ
Margulies, DH
Street, JM
Yuen, PST
Qi, CF
Krzewski, K
Coligan, JE
AF Voss, Oliver H.
Murakami, Yousuke
Pena, Mirna Y.
Lee, Ha-Na
Tian, Linjie
Margulies, David H.
Street, Jonathan M.
Yuen, Peter S. T.
Qi, Chen-Feng
Krzewski, Konrad
Coligan, John E.
TI Lipopolysaccharide-Induced CD300b Receptor Binding to Toll-like Receptor
4 Alters Signaling to Drive Cytokine Responses that Enhance Septic Shock
SO IMMUNITY
LA English
DT Article
ID APOPTOTIC CELLS; AMPLIFIES INFLAMMATION; ACTIVATING RECEPTOR; IL-10
PRODUCTION; IMMUNE-SYSTEM; PROTECTS MICE; CD14; LPS; SEPSIS; MACROPHAGES
AB Receptor CD300b is implicated in regulating the immune response to bacterial infection by an unknown mechanism. Here, we identified CD300b as a lipopolysaccharide (LPS)-binding receptor and determined the mechanism underlying CD300b augmentation of septic shock. In vivo depletion and adoptive transfer studies identified CD300b-expressing macrophages as the key cell type augmenting sepsis. We showed that CD300b, and its adaptor DAP12, associated with Toll-like receptor 4 (TLR4) upon LPS binding, thereby enhancing TLR4-adaptor MyD88- and TRIF-dependent signaling that resulted in an elevated pro-inflammatory cytokine storm. LPS engagement of the CD300b-TLR4 complex led to the recruitment and activation of spleen tyrosine kinase (Syk) and phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K). This resulted in an inhibition of the ERK1/2 protein kinase-and NF-kappa B transcription factor-mediated signaling pathways, which subsequently led to a reduced interleukin-10 (IL-10) production. Collectively, our data describe a mechanism of TLR4 signaling regulated by CD300b in myeloid cells in response to LPS.
C1 [Voss, Oliver H.; Murakami, Yousuke; Pena, Mirna Y.; Lee, Ha-Na; Tian, Linjie; Krzewski, Konrad; Coligan, John E.] NIAID, Receptor Cell Biol Sect, Immunogenet Lab, NIH, Rockville, MD 20852 USA.
[Margulies, David H.] NIAID, Mol Biol Sect, Immunol Lab, NIH, Bethesda, MD 20814 USA.
[Street, Jonathan M.; Yuen, Peter S. T.] NIDDK, Renal Diagnost & Therapeut Unit, NIH, Bethesda, MD 20814 USA.
[Qi, Chen-Feng] NIAID, Pathol Core, Immunogenet Lab, NIH, Rockville, MD 20852 USA.
RP Coligan, JE (reprint author), NIAID, Receptor Cell Biol Sect, Immunogenet Lab, NIH, Rockville, MD 20852 USA.
EM jcoligan@niaid.nih.gov
RI Yuen, Peter/B-1954-2008
OI Yuen, Peter/0000-0001-9557-3909
FU intramural programs of the National Institute of Allergy and Infectious
Diseases (NIAID)
FX We thank Robert Star (NIAID/NIH) for providing us with the CLP
methodology. We further thank Kannan Natarajan and Lisa Boyd for
assistance with the SPR analyses. We also thank Herbert Morse III, Susan
Pierce, and Louis Thomas for their critical comments and advice. This
study was supported by the intramural programs of the National Institute
of Allergy and Infectious Diseases (NIAID).
NR 40
TC 3
Z9 3
U1 6
U2 8
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1074-7613
EI 1097-4180
J9 IMMUNITY
JI Immunity
PD JUN 21
PY 2016
VL 44
IS 6
BP 1365
EP 1378
DI 10.1016/j.immuni.2016.05.005
PG 14
WC Immunology
SC Immunology
GA DP2SE
UT WOS:000378341200015
PM 27261276
ER
PT J
AU Knudsen, AB
Zauber, AG
Rutter, CM
Naber, SK
Doria-Rose, VP
Pabiniak, C
Johanson, C
Fischer, SE
Lansdorp-Vogelaar, I
Kuntz, KM
AF Knudsen, Amy B.
Zauber, Ann G.
Rutter, Carolyn M.
Naber, Steffie K.
Doria-Rose, V. Paul
Pabiniak, Chester
Johanson, Colden
Fischer, Sara E.
Lansdorp-Vogelaar, Iris
Kuntz, Karen M.
TI Estimation of Benefits, Burden, and Harms of Colorectal Cancer Screening
Strategies Modeling Study for the US Preventive Services Task Force
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Review
ID FECAL-OCCULT-BLOOD; RANDOMIZED CONTROLLED-TRIAL; COST-EFFECTIVENESS
ANALYSIS; FLEXIBLE SIGMOIDOSCOPY; CT COLONOGRAPHY; LARGE-INTESTINE;
LARGE-BOWEL; NEGATIVE COLONOSCOPY; POPULATION; MORTALITY
AB IMPORTANCE The US Preventive Services Task Force (USPSTF) is updating its 2008 colorectal cancer (CRC) screening recommendations.
OBJECTIVE To inform the USPSTF by modeling the benefits, burden, and harms of CRC screening strategies; estimating the optimal ages to begin and end screening; and identifying a set of model-recommendable strategies that provide similar life-years gained (LYG) and a comparable balance between LYG and screening burden.
DESIGN, SETTING, AND PARTICIPANTS Comparative modeling with 3 microsimulation models of a hypothetical cohort of previously unscreened US 40-year-olds with no prior CRC diagnosis.
EXPOSURES Screening with sensitive guaiac-based fecal occult blood testing, fecal immunochemical testing (FIT), multitarget stool DNA testing, flexible sigmoidoscopy with or without stool testing, computed tomographic colonography (CTC), or colonoscopy starting at age 45, 50, or 55 years and ending at age 75, 80, or 85 years. Screening intervals varied by modality. Full adherence for all strategies was assumed.
MAIN OUTCOMES AND MEASURES Life-years gained compared with no screening (benefit), lifetime number of colonoscopies required (burden), lifetime number of colonoscopy complications (harms), and ratios of incremental burden and benefit (efficiency ratios) per 1000 40-year-olds.
RESULTS The screening strategies provided LYG in the range of 152 to 313 per 1000 40-year-olds. Lifetime colonoscopy burden per 1000 persons ranged from fewer than 900 (FIT every 3 years from ages 55-75 years) to more than 7500 (colonoscopy screening every 5 years from ages 45-85 years). Harm from screening was at most 23 complications per 1000 persons screened. Strategies with screening beginning at age 50 years generally provided more LYG as well as more additional LYG per additional colonoscopy than strategies with screening beginning at age 55 years. There were limited empirical data to support a start age of 45 years. For persons adequately screened up to age 75 years, additional screening yielded small increases in LYG relative to the increase in colonoscopy burden. With screening from ages 50 to 75 years, 4 strategies yielded a comparable balance of screening burden and similar LYG (median LYG per 1000 across the models): colonoscopy every 10 years (270 LYG); sigmoidoscopy every 10 years with annual FIT (256 LYG); CTC every 5 years (248 LYG); and annual FIT (244 LYG).
CONCLUSIONS AND RELEVANCE In this microsimulation modeling study of a previously unscreened population undergoing CRC screening that assumed 100% adherence, the strategies of colonoscopy every 10 years, annual FIT, sigmoidoscopy every 10 years with annual FIT, and CTC every 5 years performed from ages 50 through 75 years provided similar LYG and a comparable balance of benefit and screening burden.
C1 [Zauber, Ann G.; Fischer, Sara E.] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, 485 Lexington Ave,Second Floor, New York, NY 10017 USA.
[Knudsen, Amy B.; Johanson, Colden] Massachusetts Gen Hosp, Dept Radiol, Inst Technol Assessment, Boston, MA USA.
[Rutter, Carolyn M.] RAND Corp, Santa Monica, CA USA.
[Naber, Steffie K.; Lansdorp-Vogelaar, Iris] Erasmus MC, Dept Publ Hlth, Rotterdam, Netherlands.
[Doria-Rose, V. Paul] NCI, Div Canc Control & Populat Sci, Rockville, MD USA.
[Pabiniak, Chester] Grp Hlth Res Inst, Seattle, WA USA.
[Kuntz, Karen M.] Univ Minnesota, Sch Publ Hlth, Dept Hlth Policy & Management, Minneapolis, MN USA.
[Johanson, Colden] Optum, Boston, MA USA.
RP Zauber, AG (reprint author), Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, 485 Lexington Ave,Second Floor, New York, NY 10017 USA.
EM zaubera@mskcc.org
OI Doria-Rose, Vincent/0000-0002-8802-5143
FU National Cancer Institute (NCI) of the National Institutes of Health
(NIH) [U01CA152959]; NCI Cancer Center Support Grant [P30CA008748]
FX This analysis was supported by the National Cancer Institute (NCI) of
the National Institutes of Health (NIH) (through a supplement from the
Agency for Healthcare Research and Quality [AHRQ]) under award
U01CA152959. Dr Zauber was also supported in part by a NCI Cancer Center
Support Grant under award P30CA008748.
NR 69
TC 15
Z9 15
U1 2
U2 4
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 0098-7484
EI 1538-3598
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD JUN 21
PY 2016
VL 315
IS 23
BP 2595
EP 2609
DI 10.1001/jama.2016.6828
PG 15
WC Medicine, General & Internal
SC General & Internal Medicine
GA DP2GQ
UT WOS:000378306700022
PM 27305518
ER
PT J
AU Kamhawi, S
Coutinho-Abreu, IV
AF Kamhawi, Shaden
Coutinho-Abreu, Iliano V.
TI VSG overcomes an early barrier to survival of African trypanosomes in
tsetse flies
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Editorial Material
ID SAND FLY VECTORS; PHLEBOTOMUS-PAPATASI; PERITROPHIC MATRIX; PARASITE
CHITINASE; NATURAL VECTOR; AEDES-AEGYPTI; MIDGUT; TRANSMISSION
C1 [Kamhawi, Shaden; Coutinho-Abreu, Iliano V.] NIAID, Vector Mol Biol Sect, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA.
RP Kamhawi, S (reprint author), NIAID, Vector Mol Biol Sect, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA.
EM skamhawi@niaid.nih.gov
NR 20
TC 0
Z9 0
U1 6
U2 6
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD JUN 21
PY 2016
VL 113
IS 25
BP 6821
EP 6823
DI 10.1073/pnas.1607008113
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DP1TN
UT WOS:000378272400026
PM 27286826
ER
PT J
AU Werner-Allen, JW
DuMond, JF
Levine, RL
Bax, A
AF Werner-Allen, Jon W.
DuMond, Jenna F.
Levine, Rodney L.
Bax, Ad
TI Toxic Dopamine Metabolite DOPAL Forms an Unexpected Dicatechol Pyrrole
Adduct with Lysines of alpha-Synuclein
SO ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
LA English
DT Article
DE amyloid disease; covalent modification; oxidative stress; Paal-Knorr
synthesis; Parkinson's disease
ID PARKINSONS-DISEASE; IN-VIVO; AGGREGATION;
3,4-DIHYDROXYPHENYLACETALDEHYDE; PRODUCTS; PROTEINS
AB Parkinson's disease has long been known to involve the loss of dopaminergic neurons in the substantia nigra and the coincidental appearance of Lewy bodies containing oligomerized forms of alpha-synuclein. The "catecholaldehyde hypothesis" posits a causal link between these two central pathologies mediated by 3,4-dihydroxyphenylacetaldehyde (DOPAL), the most toxic dopamine metabolite. Here we determine the structure of the dominant product in reactions between DOPAL and alpha-synuclein, a dicatechol pyrrole lysine adduct. This novel modification results from the addition of two DOPAL molecules to the Lys sidechain amine through their aldehyde moieties and the formation of a new carbon-carbon bond between their alkyl chains to generate a pyrrole ring. The product is detectable at low concentrations of DOPAL and its discovery should provide a valuable chemical basis for future studies of DOPAL-induced crosslinking of alpha-synuclein.
C1 [Werner-Allen, Jon W.; Bax, Ad] NIDDK, Chem Phys Lab, Bethesda, MD 20892 USA.
[DuMond, Jenna F.; Levine, Rodney L.] NHLBI, Biochem Lab, NIH, Bldg 3, Bethesda, MD 20892 USA.
RP Bax, A (reprint author), NIDDK, Chem Phys Lab, Bethesda, MD 20892 USA.; Levine, RL (reprint author), NHLBI, Biochem Lab, NIH, Bldg 3, Bethesda, MD 20892 USA.
EM rlevine@nih.gov; bax@nih.gov
RI Levine, Rodney/D-9885-2011
FU National Institute of Diabetes and Digestive and Kidney Diseases;
National Heart, Lung, National Institutes of Health
FX We thank Jinfa Ying for technical help, Daniel Mulvihill (University of
Kent) for the NatB acetyltransferase construct, the NIDDK Advanced
Spectrometry Core for preliminary data collection, and Richard Glass
(University of Arizona), S. Bruce King (Wake Forest University), Kenneth
Kirk, Vincent Cole, and Rolf Swenson (National Institutes of Health),
and Sanford Markey, W. Gary Mallard, and Edward White (National
Institutes of Standards and Technology) for their advice. This work was
supported by the Intramural Research Programs of the National Institute
of Diabetes and Digestive and Kidney Diseases and the National Heart,
Lung, National Institutes of Health.
NR 22
TC 1
Z9 1
U1 4
U2 5
PU WILEY-V C H VERLAG GMBH
PI WEINHEIM
PA POSTFACH 101161, 69451 WEINHEIM, GERMANY
SN 1433-7851
EI 1521-3773
J9 ANGEW CHEM INT EDIT
JI Angew. Chem.-Int. Edit.
PD JUN 20
PY 2016
VL 55
IS 26
BP 7374
EP 7378
DI 10.1002/anie.201600277
PG 5
WC Chemistry, Multidisciplinary
SC Chemistry
GA DV6WI
UT WOS:000383077400007
PM 27158766
ER
PT J
AU Cilli, P
Ventura, I
Minoprio, A
Meccia, E
Martire, A
Wilson, SH
Bignami, M
Mazzei, F
AF Cilli, Piera
Ventura, Ilenia
Minoprio, Anna
Meccia, Ettore
Martire, Alberto
Wilson, Samuel H.
Bignami, Margherita
Mazzei, Filomena
TI Oxidized dNTPs and the OGG1 and MUTYH DNA glycosylases combine to induce
CAG/CTG repeat instability
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID BASE EXCISION-REPAIR; PURINE NUCLEOSIDE TRIPHOSPHATASE; KNOCK-IN MICE;
HUNTINGTONS-DISEASE; OXIDATIVE DAMAGE; POLYMERASE-BETA; CAG REPEAT;
MISMATCH RECOGNITION; REPLICATION FIDELITY; SECONDARY STRUCTURE
AB DNA trinucleotide repeat (TNR) expansion underlies several neurodegenerative disorders including Huntington's disease (HD). Accumulation of oxidized DNA bases and their inefficient processing by base excision repair (BER) are among the factors suggested to contribute to TNR expansion. In this study, we have examined whether oxidation of the purine dNTPs in the dNTP pool provides a source of DNA damage that promotes TNR expansion. We demonstrate that during BER of 8-oxoguanine (8-oxodG) in TNR sequences, DNA polymerase beta (POL beta) can incorporate 8-oxodGMP with the formation of 8-oxodG:C and 8-oxodG:A mispairs. Their processing by the OGG1 and MUTYH DNA glycosylases generates closely spaced incisions on opposite DNA strands that are permissive for TNR expansion. Evidence in HD model R6/2 mice indicates that these DNA glycosylases are present in brain areas affected by neurodegeneration. Consistent with prevailing oxidative stress, the same brain areas contained increased DNA 8-oxodG levels and expression of the p53-inducible ribonucleotide reductase. Our in vitro and in vivo data support a model where an oxidized dNTPs pool together with aberrant BER processing contribute to TNR expansion in non-replicating cells.
C1 [Cilli, Piera; Ventura, Ilenia; Minoprio, Anna; Meccia, Ettore; Bignami, Margherita; Mazzei, Filomena] Ist Super Sanita, Dept Environm & Primary Prevent, I-00161 Rome, Italy.
[Cilli, Piera] Univ Rome Tre, Dept Sci, I-00154 Rome, Italy.
[Martire, Alberto] Ist Super Sanita, Dept Drug Safety & Evaluat, I-00161 Rome, Italy.
[Wilson, Samuel H.] NIEHS, Genome Integr & Struct Biol Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.
RP Bignami, M; Mazzei, F (reprint author), Ist Super Sanita, Dept Environm & Primary Prevent, I-00161 Rome, Italy.
EM Margherita.bignami@gmail.com; filomena.mazzei@iss.it
FU Associazione Italiana Ricerca sul Cancro [11755]; Ministry of Health,
Project 'Malattie Rare'; Intramural Research Program of the US National
Institutes of Health, NIEHS [Z01 ES050158, ES050159]; Istituto Superiore
di Sanita
FX Associazione Italiana Ricerca sul Cancro [11755]; Ministry of Health,
Project 'Malattie Rare' (to M.B. and F.M.); Intramural Research Program
of the US National Institutes of Health, NIEHS [Z01 ES050158, ES050159
to S.H.W.]. Funding for open access charge: Istituto Superiore di Sanita
NR 58
TC 2
Z9 2
U1 1
U2 3
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
EI 1362-4962
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD JUN 20
PY 2016
VL 44
IS 11
BP 5190
EP 5203
DI 10.1093/nar/gkw170
PG 14
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA DR2SB
UT WOS:000379753100028
PM 26980281
ER
PT J
AU Henriksen, S
Read, JCA
AF Henriksen, Sid
Read, Jenny C. A.
TI Visual Perception: A Novel Difference Channel in Binocular Vision
SO CURRENT BIOLOGY
LA English
DT Editorial Material
ID ADAPTATION
AB A recent study provides compelling evidence that binocular vision uses two separate channels; one channel adds the images from the two eyes, and the other subtracts them.
C1 [Henriksen, Sid; Read, Jenny C. A.] Newcastle Univ, Inst Neurosci, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England.
[Henriksen, Sid] NEI, Sensorimotor Res Lab, NIH, Bldg 10, Bethesda, MD 20892 USA.
RP Henriksen, S; Read, JCA (reprint author), Newcastle Univ, Inst Neurosci, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England.; Henriksen, S (reprint author), NEI, Sensorimotor Res Lab, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM sid.henriksen@gmail.com; jenny.read@ncl.ac.uk
OI Read, Jenny/0000-0002-9029-5185
NR 14
TC 0
Z9 0
U1 1
U2 2
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0960-9822
EI 1879-0445
J9 CURR BIOL
JI Curr. Biol.
PD JUN 20
PY 2016
VL 26
IS 12
BP R500
EP R503
DI 10.1016/j.cub.2016.04.049
PG 4
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA DP7EK
UT WOS:000378661800009
PM 27326711
ER
PT J
AU Ondov, BD
Treangen, TJ
Melsted, P
Mallonee, AB
Bergman, NH
Koren, S
Phillippy, AM
AF Ondov, Brian D.
Treangen, Todd J.
Melsted, Pall
Mallonee, Adam B.
Bergman, Nicholas H.
Koren, Sergey
Phillippy, Adam M.
TI Mash: fast genome and metagenome distance estimation using MinHash
SO GENOME BIOLOGY
LA English
DT Article
DE Comparative genomics; Genomic distance; Alignment; Sequencing; Nanopore;
Metagenomics
ID SEQUENCING DATA; ALIGNMENT; RECONSTRUCTION; SIMILARITY; ALGORITHM;
MATCHES; SEARCH
AB Mash extends the MinHash dimensionality-reduction technique to include a pairwise mutation distance and P value significance test, enabling the efficient clustering and search of massive sequence collections. Mash reduces large sequences and sequence sets to small, representative sketches, from which global mutation distances can be rapidly estimated. We demonstrate several use cases, including the clustering of all 54,118 NCBI RefSeq genomes in 33 CPU h; real-time database search using assembled or unassembled Illumina, Pacific Biosciences, and Oxford Nanopore data; and the scalable clustering of hundreds of metagenomic samples by composition. Mash is freely released under a BSD license (https://github.com/marbl/mash).
C1 [Ondov, Brian D.; Treangen, Todd J.; Mallonee, Adam B.; Bergman, Nicholas H.] Natl Biodef Anal & Countermeasures Ctr, Frederick, MD USA.
[Melsted, Pall] Univ Iceland, Fac Ind Engn, Mech Engn & Comp Sci, Reykjavik, Iceland.
[Koren, Sergey; Phillippy, Adam M.] NHGRI, Genome Informat Sect, Computat & Stat Genom Branch, NIH, Bethesda, MD 20892 USA.
RP Phillippy, AM (reprint author), NHGRI, Genome Informat Sect, Computat & Stat Genom Branch, NIH, Bethesda, MD 20892 USA.
EM adam.phillippy@nih.gov
FU Intramural Research Program of the National Human Genome Research
Institute, National Institutes of Health; Department of Homeland
Security (DHS) Science and Technology Directorate (S&T) for the
management and operation of the National Biodefense Analysis and
Countermeasures Center (NBACC) [HSHQDC-07-C-00020]
FX This research was supported in part by the Intramural Research Program
of the National Human Genome Research Institute, National Institutes of
Health, and under Contract No. HSHQDC-07-C-00020 awarded by the
Department of Homeland Security (DHS) Science and Technology Directorate
(S&T) for the management and operation of the National Biodefense
Analysis and Countermeasures Center (NBACC), a Federally Funded Research
and Development Center. The views and conclusions contained in this
document are those of the authors and should not be interpreted as
necessarily representing the official policies, either expressed or
implied, of the DHS or S&T. In no event shall the DHS, NBACC, S&T, or
Battelle National Biodefense Institute (BNBI) have any responsibility or
liability for any use, misuse, inability to use, or reliance upon the
information contained herein. DHS does not endorse any products or
commercial services mentioned in this publication.
NR 55
TC 6
Z9 6
U1 6
U2 9
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1474-760X
J9 GENOME BIOL
JI Genome Biol.
PD JUN 20
PY 2016
VL 17
AR 132
DI 10.1186/s13059-016-0997-x
PG 14
WC Biotechnology & Applied Microbiology; Genetics & Heredity
SC Biotechnology & Applied Microbiology; Genetics & Heredity
GA DQ0OZ
UT WOS:000378900700001
PM 27323842
ER
PT J
AU Levin, L
Srour, S
Gartner, J
Kapitansky, O
Qutob, N
Dror, S
Golan, T
Dayan, R
Brener, R
Ziv, T
Khaled, M
Schueler-Furman, O
Samuels, Y
Levy, C
AF Levin, Lotan
Srour, Shani
Gartner, Jared
Kapitansky, Oxana
Qutob, Nouar
Dror, Shani
Golan, Tamar
Dayan, Roy
Brener, Ronen
Ziv, Tamar
Khaled, Mehdi
Schueler-Furman, Ora
Samuels, Yardena
Levy, Carmit
TI Parkin Somatic Mutations Link Melanoma and Parkinson's Disease
SO JOURNAL OF GENETICS AND GENOMICS
LA English
DT Article
DE Melanoma; Parkinson's disease; Parkin; Mutation
ID UBIQUITIN-PROTEIN LIGASE; INDEPENDENT UBIQUITINATION;
MALIGNANT-MELANOMA; BREAST-CANCER; GENES; DEGRADATION; ACTIVATION;
LANDSCAPE; DELETIONS; DOPAMINE
AB Epidemiological studies suggest a direct link between melanoma and Parkinson's disease (PD); however, the underlying molecular basis is unknown. Since mutations in Parkin are the major driver of early-onset PD and Parkin was recently reported to play a role in cancer development, we hypothesized that Parkin links melanoma and PD. By analyzing whole exome/genome sequencing of Parkin from 246 melanoma patients, we identified five non-synonymous mutations, three synonymous mutations, and one splice region variant in Parkin in 3.6% of the samples. In vitro analysis showed that wild-type Parkin plays a tumor suppressive role in melanoma development resulting in cell-cycle arrest, reduction of metabolic activity, and apoptosis. Using a mass spectrometry-based analysis, we identified potential Parkin substrates in melanoma and generated a functional protein association network. The activity of mutated Parkin was assessed by protein structure modeling and examination of Parkin E3 ligase activity. The Parkin-E28K mutation impairs Parkin ubiquitination activity and abolishes its tumor suppressive effect. Taken together, our analysis of genomic sequence and in vitro data indicate that Parkin is a potential link between melanoma and Parkinson's disease. Our findings suggest new approaches for early diagnosis and treatment against both diseases.
C1 [Levin, Lotan; Srour, Shani; Kapitansky, Oxana; Dror, Shani; Golan, Tamar; Dayan, Roy; Levy, Carmit] Tel Aviv Univ, Sackler Fac Med, Dept Human Genet & Biochem, IL-69978 Tel Aviv, Israel.
[Gartner, Jared] NCI, Surg Branch, NIH, Bldg 10, Bethesda, MD 20892 USA.
[Qutob, Nouar; Samuels, Yardena] Weizmann Inst Sci, Dept Mol Cell Biol, IL-76100 Rehovot, Israel.
[Brener, Ronen] Edith Wolfson Med Ctr, Inst Oncol, IL-5822012 Holon, Israel.
[Ziv, Tamar] Technion Israel Inst Technol, Fac Biol, Technion Smoler Prote Ctr, IL-32000 Haifa, Israel.
[Khaled, Mehdi] Inst Gustave Roussy, INSERM, U753, F-94805 Villejuif, France.
[Schueler-Furman, Ora] Hebrew Univ Jerusalem, Fac Med, Dept Microbiol & Mol Genet, Inst Med Res Israel Canada, IL-91120 Jerusalem, Israel.
RP Levy, C (reprint author), Tel Aviv Univ, Sackler Fac Med, Dept Human Genet & Biochem, IL-69978 Tel Aviv, Israel.
EM carmitlevy@post.tau.ac.il
RI khaled, mehdi/C-4854-2012
FU I-CORE [41/11]; Israel Cancer Association (ICA) [20150101]; Israel
Cancer Research Fund (ICRF) [RCBA-11706]; Fritz Thyssen Stiftung
[AZ.10.12.1.188]; Marie Curie Career Integration Grants (CIG) [293594];
Dalya Gridinger Fund; Fingerhot Carol and Lionara Fund; Shtacher Family
award
FX We would like to thank Drs. Meenhard Herlyn, Levi Garraway, and Carl
Novina for supplying melanoma cultures and the Smoler Proteomics Center
at the Technion for mass spectroscopy analyses. C.L. gratefully
acknowledges grant support from I-CORE (grant number 41/11), Mr. David
Brown through the Israel Cancer Association (ICA) (grant number
20150101), Israel Cancer Research Fund (ICRF) (grant number RCBA-11706),
Fritz Thyssen Stiftung (grant number AZ.10.12.1.188), Marie Curie Career
Integration Grants (CIG) (grant number 293594), Dalya Gridinger Fund,
Fingerhot Carol and Lionara Fund, and the Shtacher Family award.
NR 49
TC 1
Z9 1
U1 4
U2 11
PU SCIENCE PRESS
PI BEIJING
PA 16 DONGHUANGCHENGGEN NORTH ST, BEIJING 100717, PEOPLES R CHINA
SN 1673-8527
EI 1873-5533
J9 J GENET GENOMICS
JI J. Genet. Genomics
PD JUN 20
PY 2016
VL 43
IS 6
BP 369
EP 379
DI 10.1016/j.jgg.2016.05.005
PG 11
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA DP5MT
UT WOS:000378542400002
PM 27297116
ER
PT J
AU Jiang, JS
Promchan, K
Jiang, H
Awasthi, P
Marshall, H
Harned, A
Natarajan, V
AF Jiang, Jiangsong
Promchan, Kanyarat
Jiang, Hong
Awasthi, Parirokh
Marshall, Heather
Harned, Adam
Natarajan, Ven
TI Depletion of BBS Protein LZTFL1 Affects Growth and Causes Retinal
Degeneration in Mice
SO JOURNAL OF GENETICS AND GENOMICS
LA English
DT Article
DE LZTFL1; Cilium; BBSome; BBS17; Retina; AP-1
ID BARDET-BIEDL-SYNDROME; INTRAFLAGELLAR TRANSPORT; CILIA FUNCTION;
SYNDROME GENES; CORE COMPLEX; MOUSE MODEL; T-CELLS; IFT; TRAFFICKING;
PHENOTYPES
AB Bardet-Biedl syndrome (BBS) is a heterogeneous disease characterized by deficiencies in various organs that are caused by defects in genes involved in the genesis, structural maintenance, and protein trafficking of cilia. Leucine zipper transcription factor-like 1 (LZTFL1) has been identified as a BBS protein (BBS17), because patients with mutations in this gene exhibit the common BBS phenotypes. In this study, we generated a knockout mouse model to investigate the effects of LZTFL1 depletion. Lztfl1 knockout mice were born with low birth weight, reached similar weight to those of wild-type mice at 10 weeks of age, and later gained more weight than their wild-type counterparts. LZTFL1 was localized to the primary cilium of kidney cells, and the absence of LZTFL1 increased the ciliary localization of BBS9. Moreover, in the retinas of Lztfl1 knockout mice, the photoreceptor outer segment was shortened, the distal axoneme of photoreceptor connecting cilium was significantly enlarged, and rhodopsin was targeted to the outer nuclear layer. TUNEL assay showed that many of these abnormal photoreceptor cells in Lztfl1 knockout mice underwent apoptosis. Interestingly, the absence of LZTFL1 caused an abnormal increase of the adaptor protein complex 1 (AP1) in some photoreceptor cells. Based on these data, we conclude that LZTFL1 is a cilium protein and regulates animal weight and photoreceptor connecting cilium function probably by controlling microtubule assembly and protein trafficking in cilia.
C1 [Jiang, Jiangsong; Promchan, Kanyarat; Jiang, Hong; Marshall, Heather; Natarajan, Ven] Leidos Biomed Res Inc, Mol Cell Biol Lab, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
[Awasthi, Parirokh] Leidos Biomed Res Inc, Transgen Mouse Model Lab, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
[Harned, Adam] Leidos Biomed Res Inc, Electron Microscopy Lab, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
[Jiang, Hong] Univ Kentucky, Grad Ctr Toxicol, Lucille P Markey Canc Ctr, Lexington, KY 40536 USA.
RP Jiang, JS; Natarajan, V (reprint author), Leidos Biomed Res Inc, Mol Cell Biol Lab, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
EM jiangj2@mail.nih.gov; Vnatarajan@mail.nih.gov
FU National Cancer Institute, National Institutes of Health
[HHSN261200800001E]; National Institute of Allergy and Infectious
Diseases
FX This work has been funded in whole or in part with federal funds from
the National Cancer Institute, National Institutes of Health, under
contract (HHSN261200800001E), and also supported by the National
Institute of Allergy and Infectious Diseases. The content of this
publication does not necessarily reflect the views or policies of the
Department of Health and Human Services, nor does mention of trade
names, commercial products, or organizations imply endorsement by the
U.S. Government. We would like to thank Kunio Nagashima for help with
electron microscope analysis, as well as Mohammad Ishaq and other
members of the Laboratory of Molecular Cell Biology for valuable
suggestions.
NR 48
TC 1
Z9 1
U1 2
U2 3
PU SCIENCE PRESS
PI BEIJING
PA 16 DONGHUANGCHENGGEN NORTH ST, BEIJING 100717, PEOPLES R CHINA
SN 1673-8527
EI 1873-5533
J9 J GENET GENOMICS
JI J. Genet. Genomics
PD JUN 20
PY 2016
VL 43
IS 6
BP 381
EP 391
DI 10.1016/j.jgg.2015.11.006
PG 11
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA DP5MT
UT WOS:000378542400003
PM 27312011
ER
PT J
AU Halilovic, A
Schmedt, T
Benischke, AS
Hamill, C
Chen, YM
Santos, JH
Jurkunas, UV
AF Halilovic, Adna
Schmedt, Thore
Benischke, Anne-Sophie
Hamill, Cecily
Chen, Yuming
Santos, Janine Hertzog
Jurkunas, Ula V.
TI Menadione-Induced DNA Damage Leads to Mitochondrial Dysfunction and
Fragmentation During Rosette Formation in Fuchs Endothelial Corneal
Dystrophy
SO ANTIOXIDANTS & REDOX SIGNALING
LA English
DT Article
ID INDUCED OXIDATIVE STRESS; CELL-DEATH; INDUCED APOPTOSIS; MORPHOLOGY;
EXPRESSION; PROTECTS; FUSION; CLUSTERIN; DIVISION; DYNAMICS
AB Aims: Fuchs endothelial corneal dystrophy (FECD), a leading cause of age-related corneal edema requiring transplantation, is characterized by rosette formation of corneal endothelium with ensuing apoptosis. We sought to determine whether excess of mitochondrial reactive oxygen species leads to chronic accumulation of oxidative DNA damage and mitochondrial dysfunction, instigating cell death. Results: We modeled the pathognomonic rosette formation of postmitotic corneal cells by increasing endogenous cellular oxidative stress with menadione (MN) and performed a temporal analysis of its effect in normal (HCEnC, HCECi) and FECD (FECDi) cells and ex vivo specimens. FECDi and FECD ex vivo specimens exhibited extensive mtDNA and nDNA damage as detected by quantitative PCR. Exposure to MN triggered an increase in mitochondrial superoxide levels and led to mtDNA and nDNA damage, while DNA amplification was restored with NAC pretreatment. Furthermore, MN exposure led to a decrease in Delta Psi m and adenosine triphosphate levels in normal cells, while FECDi exhibited mitochondrial dysfunction at baseline. Mitochondrial fragmentation and cytochrome c release were detected in FECD tissue and after MN treatment of HCEnCs. Furthermore, cleavage of caspase-9 and caspase-3 followed MN-induced cytochrome c release in HCEnCs. Innovation: This study provides the first line of evidence that accumulation of oxidative DNA damage leads to rosette formation, loss of functionally intact mitochondria via fragmentation, and subsequent cell death during postmitotic cell degeneration of ocular tissue. Conclusion: MN induced rosette formation, along with mtDNA and nDNA damage, mitochondrial dysfunction, and fragmentation, leading to activation of the intrinsic apoptosis via caspase cleavage and cytochrome c release.
C1 [Halilovic, Adna; Schmedt, Thore; Benischke, Anne-Sophie; Hamill, Cecily; Chen, Yuming; Jurkunas, Ula V.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Schepens Eye Res Inst, 20 Staniford St, Boston, MA 02114 USA.
[Santos, Janine Hertzog] Rutgers State Univ, New Jersey Med Sch Rutgers, Dept Physiol & Pharmacol, Piscataway, NJ 08855 USA.
[Santos, Janine Hertzog] NIEHS, Epigenet & Stem Cell Biol Lab, POB 12233, Res Triangle Pk, NC 27709 USA.
RP Jurkunas, UV (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Schepens Eye Res Inst, 20 Staniford St, Boston, MA 02114 USA.
EM ula_jurkunas@meei.harvard.edu
FU NEI/NIH [R01 EY020581]
FX This work was supported by NEI/NIH R01 EY020581.
NR 47
TC 2
Z9 2
U1 4
U2 7
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1523-0864
EI 1557-7716
J9 ANTIOXID REDOX SIGN
JI Antioxid. Redox Signal.
PD JUN 20
PY 2016
VL 24
IS 18
BP 1072
EP 1083
DI 10.1089/ars.2015.6532
PG 12
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA DP2RE
UT WOS:000378336900004
PM 26935406
ER
PT J
AU Kim, JW
Yang, HJ
Oel, AP
Brooks, MJ
Jia, L
Plachetzki, DC
Li, W
Allison, WT
Swaroop, A
AF Kim, Jung-Woong
Yang, Hyun-Jin
Oel, Adam Phillip
Brooks, Matthew John
Jia, Li
Plachetzki, David Charles
Li, Wei
Allison, William Ted
Swaroop, Anand
TI Recruitment of Rod Photoreceptors from Short-Wavelength-Sensitive Cones
during the Evolution of Nocturnal Vision in Mammals
SO DEVELOPMENTAL CELL
LA English
DT Article
ID MOUSE RETINA; VERTEBRATE PHOTORECEPTORS; TRANSCRIPTION FACTORS; TEMPORAL
EXPRESSION; VISUAL PIGMENTS; COLOR-VISION; CELLS; NRL; PRECURSORS;
ZEBRAFISH
AB Vertebrate ancestors had only cone-like photoreceptors. The duplex retina evolved in jawless vertebrates with the advent of highly photosensitive rod-like photoreceptors. Despite cones being the arbiters of high-resolution color vision, rods emerged as the dominant photoreceptor in mammals during a nocturnal phase early in their evolution. We investigated the evolutionary and developmental origins of rods in two divergent vertebrate retinas. In mice, we discovered genetic and epigenetic vestiges of short-wavelength cones in developing rods, and cell-lineage tracing validated the genesis of rods from S cones. Curiously, rods did not derive from S cones in zebrafish. Our study illuminates several questions regarding the evolution of duplex retina and supports the hypothesis that, in mammals, the S-cone lineage was recruited via the Maf-family transcription factor NRL to augment rod photoreceptors. We propose that this developmental mechanism allowed the adaptive exploitation of scotopic niches during the nocturnal bottleneck early in mammalian evolution.
C1 [Kim, Jung-Woong; Yang, Hyun-Jin; Brooks, Matthew John; Swaroop, Anand] NEI, Neurobiol Neurodegenerat & Repair Lab, NIH, Bethesda, MD 20892 USA.
[Kim, Jung-Woong] Chung Ang Univ, Coll Nat Sci, Dept Life Sci, Seoul 156756, South Korea.
[Oel, Adam Phillip; Allison, William Ted] Univ Alberta, Dept Biol Sci, Edmonton, AB T6G 2E9, Canada.
[Jia, Li; Li, Wei] NEI, Retinal Neurophysiol Sect, NIH, Bethesda, MD 20892 USA.
[Plachetzki, David Charles] Univ New Hampshire, Dept Mol Cellular & Biomed Sci, Durham, NH 03824 USA.
RP Swaroop, A (reprint author), NEI, Neurobiol Neurodegenerat & Repair Lab, NIH, Bethesda, MD 20892 USA.; Allison, WT (reprint author), Univ Alberta, Dept Biol Sci, Edmonton, AB T6G 2E9, Canada.
EM ted.allison@ualberta.ca; swaroopa@nei.nih.gov
OI Allison, Ted/0000-0002-8461-4864
FU Intramural Research Program of the National Eye Institute [EY000450,
EY000474]; Natural Sciences & Engineering Research Council of Canada;
National Research Foundation of Korea [NRF-2015 R1C1A1A01055466]
FX We are grateful to Douglas Forrest for advice and discussions, Tudor
Badea for Rosa26-iAP mouse, Rafael Vilasmil for flow cytometry, and
Robert Farris for imaging support. We thank Alexis Boleda, Sam Perez,
and Genomatix (Claudia Gugenmus, Tanja Druke, Martin Seifert) for
assistance in some of the next-generation sequencing data analysis. We
acknowledge Hao Wang and Michele DuVal for generating transgenic
zebrafish. This research was supported by the Intramural Research
Program of the National Eye Institute (EY000450, EY000474), a Discovery
Accelerator Grant from the Natural Sciences & Engineering Research
Council of Canada, and the National Research Foundation of Korea
(NRF-2015 R1C1A1A01055466). This work utilized the high-performance
computational resources of the HPC Biowulf cluster at NIH
(http://hpc.nih.gov).
NR 74
TC 8
Z9 8
U1 7
U2 19
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1534-5807
EI 1878-1551
J9 DEV CELL
JI Dev. Cell
PD JUN 20
PY 2016
VL 37
IS 6
BP 520
EP 532
DI 10.1016/j.devcel.2016.05.023
PG 13
WC Cell Biology; Developmental Biology
SC Cell Biology; Developmental Biology
GA DP0UB
UT WOS:000378204200007
PM 27326930
ER
PT J
AU Ahmad, F
Chung, YW
Tang, Y
Hockman, SC
Liu, SW
Khan, Y
Huo, K
Billings, E
Amar, MJ
Remaley, AT
Manganiello, VC
AF Ahmad, Faiyaz
Chung, Youn Wook
Tang, Yan
Hockman, Steven C.
Liu, Shiwei
Khan, Yusuf
Huo, Kevin
Billings, Eric
Amar, Marcelo J.
Remaley, Alan T.
Manganiello, Vincent C.
TI Phosphodiesterase 3B (PDE3B) regulates NLRP3 inflammasome in adipose
tissue
SO SCIENTIFIC REPORTS
LA English
DT Article
ID ACTIVATED PROTEIN-KINASE; GAMMA-INDUCING FACTOR; SMOOTH-MUSCLE-CELLS;
NF-KAPPA-B; INSULIN-RESISTANCE; ENERGY HOMEOSTASIS; OBESE MICE; BETA;
MACROPHAGES; SENSITIVITY
AB Activation of inflammation in white adipose tissue (WAT), includes infiltration/expansion of WAT macrophages, contributes pathogenesis of obesity, insulin resistance, and metabolic syndrome. The inflammasome comprises an intracellular sensor (NLR), caspase-1 and the adaptor ASC. Inflammasome activation leads to maturation of caspase-1 and processing of IL1 beta, contributing to many metabolic disorders and directing adipocytes to a more insulin-resistant phenotype. Ablation of PDE3B in WAT prevents inflammasome activation by reducing expression of NLRP3, caspase-1, ASC, AIM2, TNF alpha, IL1 beta and proinflammatory genes. Following IP injection of lipopolysaccharide (LPS), serum levels of IL1 beta and TNF alpha were reduced in PDE3B(-/-)mice compared to WT. Activation of signaling cascades, which mediate inflammasome responses, were modulated in PDE3B(-/-)mice WAT, including smad, NFAT, NFkB, and MAP kinases. Moreover, expression of chemokine CCL2, MCP-1 and its receptor CCR2, which play an important role in macrophage chemotaxis, were reduced in WAT of PDE3B(-/-)mice. In addition, atherosclerotic plaque formation was significantly reduced in the aorta of apoE(-/-)/PDE3B(-/-) and LDL-R-/-/PDE3B(-/-)mice compared to apoE(-/-) and LDL-R(-/-)mice, respectively. Obesity-induced changes in serum-cholesterol were blocked in PDE3B(-/-)mice. Collectively, these data establish a role for PDE3B in modulating inflammatory response, which may contribute to a reduced inflammatory state in adipose tissue.
C1 [Ahmad, Faiyaz; Chung, Youn Wook; Tang, Yan; Hockman, Steven C.; Liu, Shiwei; Khan, Yusuf; Huo, Kevin; Amar, Marcelo J.; Remaley, Alan T.; Manganiello, Vincent C.] NHLBI, Cardiovasc & Pulm Branch, NIH, Bldg 10, Bethesda, MD 20892 USA.
[Billings, Eric] NHLBI, Lab Computat Biol, NIH, Bldg 10, Bethesda, MD 20892 USA.
RP Ahmad, F (reprint author), NHLBI, Cardiovasc & Pulm Branch, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM AhmadF@NHLBI.NIH.gov
FU Intramural Research Program, National Heart, Lung and Blood Institute,
National Institutes of Health, Bethesda, MD, USA
FX These studies were supported by the Intramural Research Program,
National Heart, Lung and Blood Institute, National Institutes of Health,
Bethesda, MD, USA. The manuscript was completed following Dr.
Manganiello's death. Dr. Joel Moss (NHLBI, NIH) assumed responsibility
for its content. We also thank Dr. Matthew Movsesian for his careful
reading of the manuscript and providing constructive comments.
NR 53
TC 0
Z9 0
U1 4
U2 5
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2045-2322
J9 SCI REP-UK
JI Sci Rep
PD JUN 20
PY 2016
VL 6
AR 28056
DI 10.1038/srep28056
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DP1CD
UT WOS:000378227100001
PM 27321128
ER
PT J
AU Mullooly, M
Pfeiffer, RM
Nyante, SJ
Heckman-Stoddard, BM
Perloff, M
Jatoi, I
Brinton, LA
Bowles, EJA
Hoover, RN
Glass, A
de Gonzalez, AB
Sherman, ME
Gierach, GL
AF Mullooly, Maeve
Pfeiffer, Ruth M.
Nyante, Sarah J.
Heckman-Stoddard, Brandy M.
Perloff, Marjorie
Jatoi, Ismail
Brinton, Louise A.
Bowles, Erin J. Aiello
Hoover, Robert N.
Glass, Andrew
de Gonzalez, Amy Berrington
Sherman, Mark E.
Gierach, Gretchen L.
TI Mammographic Density as a Biosensor of Tamoxifen Effectiveness in
Adjuvant Endocrine Treatment of Breast Cancer: Opportunities and
Implications
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Editorial Material
ID WOMEN; RISK; TRIAL; CYP2D6; REDUCTION; THERAPY
C1 [Mullooly, Maeve; Pfeiffer, Ruth M.; Heckman-Stoddard, Brandy M.; Perloff, Marjorie; Brinton, Louise A.; Hoover, Robert N.; de Gonzalez, Amy Berrington; Sherman, Mark E.; Gierach, Gretchen L.] NCI, Bethesda, MD 20892 USA.
[Nyante, Sarah J.] Univ N Carolina, Sch Med, Chapel Hill, NC USA.
[Jatoi, Ismail] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA.
[Bowles, Erin J. Aiello] Grp Hlth Res Inst, Seattle, WA USA.
[Glass, Andrew] Kaiser Permanente Northwest Ctr Hlth Res, Portland, OR USA.
RP Mullooly, M (reprint author), NCI, Bethesda, MD 20892 USA.
RI Gierach, Gretchen/E-1817-2016
OI Gierach, Gretchen/0000-0002-0165-5522
NR 30
TC 1
Z9 1
U1 2
U2 3
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD JUN 20
PY 2016
VL 34
IS 18
BP 2093
EP +
DI 10.1200/JCO.2015.64.4492
PG 7
WC Oncology
SC Oncology
GA DN9DU
UT WOS:000377380300006
PM 27022110
ER
PT J
AU Henriksen, S
Tanabe, S
Cumming, B
AF Henriksen, Sid
Tanabe, Seiji
Cumming, Bruce
TI Disparity processing in primary visual cortex
SO PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES
LA English
DT Review
DE binocular disparity; striate cortex; depth perception
ID CAT STRIATE CORTEX; STEREOSCOPIC DEPTH-PERCEPTION; LATERAL
GENICULATE-NUCLEUS; BINOCULAR DISPARITY; COMPLEX CELLS; V1 NEURONS;
HORIZONTAL DISPARITY; RECEPTIVE-FIELDS; ENERGY-MODEL; MACAQUE V1
AB The first step in binocular stereopsis is to match features on the left retina with the correct features on the right retina, discarding 'false' matches. The physiological processing of these signals starts in the primary visual cortex, where the binocular energy model has been a powerful framework for understanding the underlying computation. For this reason, it is often used when thinking about how binocular matching might be performed beyond striate cortex. But this step depends critically on the accuracy of the model, and real V1 neurons show several properties that suggest they may be less sensitive to false matches than the energy model predicts. Several recent studies provide empirical support for an extended version of the energy model, in which the same principles are used, but the responses of single neurons are described as the sum of several subunits, each of which follows the principles of the energy model. These studies have significantly improved our understanding of the role played by striate cortex in the stereo correspondence problem.
This article is part of the themed issue 'Vision in our three-dimensional world'.
C1 [Henriksen, Sid; Cumming, Bruce] NEI, Lab Sensorimotor Res, NIH, Bethesda, MD 20892 USA.
[Tanabe, Seiji] Univ Virginia, EEG Lab, Hlth Syst, Charlottesville, VA USA.
RP Cumming, B (reprint author), NEI, Lab Sensorimotor Res, NIH, Bethesda, MD 20892 USA.
EM bgc@lsr.nei.nih.gov
FU National Institutes of Health, National Eye Institute
FX This work was supported by the Intramural Research Program of the
National Institutes of Health, National Eye Institute.
NR 49
TC 3
Z9 3
U1 4
U2 5
PU ROYAL SOC
PI LONDON
PA 6-9 CARLTON HOUSE TERRACE, LONDON SW1Y 5AG, ENGLAND
SN 0962-8436
EI 1471-2970
J9 PHILOS T R SOC B
JI Philos. Trans. R. Soc. B-Biol. Sci.
PD JUN 19
PY 2016
VL 371
IS 1697
AR 20150255
DI 10.1098/rstb.2015.0255
PG 12
WC Biology
SC Life Sciences & Biomedicine - Other Topics
GA DO3TQ
UT WOS:000377704900004
ER
PT J
AU Murphy, AP
Leopold, DA
Humphreys, GW
Welchman, AE
AF Murphy, Aidan P.
Leopold, David A.
Humphreys, Glyn W.
Welchman, Andrew E.
TI Lesions to right posterior parietal cortex impair visual depth
perception from disparity but not motion cues
SO PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES
LA English
DT Article
DE depth perception; binocular vision; structure from motion; bistable;
parietal cortex
ID STRUCTURE-FROM-MOTION; COST FUNCTION MASKING; BINOCULAR-RIVALRY;
BISTABLE PERCEPTION; STEREOSCOPIC VISION; PREFRONTAL CORTEX; HUMAN
BRAIN; SPATIAL NORMALIZATION; PSYCHOMETRIC FUNCTION; DOMINANCE DURATIONS
AB The posterior parietal cortex (PPC) is understood to be active when observers perceive three-dimensional (3D) structure. However, it is not clear howcentral this activity is in the construction of 3D spatial representations. Here, we examine whether PPC is essential for two aspects of visual depth perception by testing patients with lesions affecting this region. First, we measured subjects' ability to discriminate depth structure in various 3D surfaces and objects using binocular disparity. Patients with lesions to right PPC (N = 3) exhibited marked perceptual deficits on these tasks, whereas those with left hemisphere lesions (N = 2) were able to reliably discriminate depth as accurately as control subjects. Second, we presented an ambiguous 3D stimulus defined by structure from motion to determine whether PPC lesions influence the rate of bistable perceptual alternations. Patients' percept durations for the 3D stimulus were generally within a normal range, although the two patients with bilateral PPC lesions showed the fastest perceptual alternation rates in our sample. Intermittent stimulus presentation reduced the reversal rate similarly across subjects. Together, the results suggest that PPC plays a causal role in both inferring and maintaining the perception of 3D structure with stereopsis supported primarily by the right hemisphere, but do not lend support to the view that PPC is a critical contributor to bistable perceptual alternations.
This article is part of the themed issue 'Vision in our three-dimensional world'.
C1 [Murphy, Aidan P.; Leopold, David A.] NIMH, Sect Cognit Neurophysiol & Imaging, Neuropsychol Lab, Bethesda, MD 20838 USA.
[Murphy, Aidan P.; Humphreys, Glyn W.; Welchman, Andrew E.] Univ Birmingham, Sch Psychol, Birmingham B15 2TT, W Midlands, England.
[Humphreys, Glyn W.] Univ Oxford, Dept Expt Psychol, S Parks Rd, Oxford OX1 3UD, England.
[Welchman, Andrew E.] Univ Cambridge, Dept Psychol, Downing St, Cambridge CB2 3EB, England.
RP Murphy, AP (reprint author), NIMH, Sect Cognit Neurophysiol & Imaging, Neuropsychol Lab, Bethesda, MD 20838 USA.; Murphy, AP (reprint author), Univ Birmingham, Sch Psychol, Birmingham B15 2TT, W Midlands, England.
EM murphyap@mail.nih.gov
OI Leopold, David/0000-0002-1345-6360
FU Wellcome Trust-NIH [WT091467MA]; Wellcome Trust [095183/Z/10/Z]; MRC;
Stroke Association; National Institutes of Health
FX This research was supported by a Wellcome Trust-NIH PhD studentship
(WT091467MA) to A.P.M., a Wellcome Trust Fellowship (095183/Z/10/Z) to
A.E.W., and grants from the MRC and the Stroke Association to G.W.H.
D.A.L. and A.P.M. are supported by the Intramural program of the
National Institutes of Health.
NR 116
TC 2
Z9 2
U1 3
U2 4
PU ROYAL SOC
PI LONDON
PA 6-9 CARLTON HOUSE TERRACE, LONDON SW1Y 5AG, ENGLAND
SN 0962-8436
EI 1471-2970
J9 PHILOS T R SOC B
JI Philos. Trans. R. Soc. B-Biol. Sci.
PD JUN 19
PY 2016
VL 371
IS 1697
AR 20150263
DI 10.1098/rstb.2015.0263
PG 17
WC Biology
SC Life Sciences & Biomedicine - Other Topics
GA DO3TQ
UT WOS:000377704900012
ER
PT J
AU Krebs, SJ
Slike, BM
Sithinamsuwan, P
Allen, IE
Chalermchai, T
Tipsuk, S
Phanuphak, N
Jagodzinski, L
Kim, JH
Ananworanich, J
Marovich, MA
Valcour, VG
AF Krebs, Shelly J.
Slike, Bonnie M.
Sithinamsuwan, Pasiri
Allen, Isabel E.
Chalermchai, Thep
Tipsuk, Somporn
Phanuphak, Nittaya
Jagodzinski, Linda
Kim, Jerome H.
Ananworanich, Jintanat
Marovich, Mary A.
Valcour, Victor G.
CA SEARCH 011 Study Team
TI Sex differences in soluble markers vary before and after the initiation
of antiretroviral therapy in chronically HIV-infected individuals
SO AIDS
LA English
DT Article
DE cognition; cytokines; HIV; neopterin; sCD14; sex; soluble factors
ID IMMUNODEFICIENCY-VIRUS-INFECTION; CENTRAL-NERVOUS-SYSTEM;
CEREBROSPINAL-FLUID; IMMUNE ACTIVATION; PREDICT MORTALITY; T-CELLS; C
VIRUS; AIDS; NEOPTERIN; INFLAMMATION
AB Objective: To evaluate differences in soluble inflammatory markers between chronically HIV-infected men and women, with or without cognitive impairment, and in response to treatment.
Design: Soluble biomarkers were measured in cryopreserved plasma and cerebrospinal fluid (CSF) of 60 treatment-nave individuals (25 men and 35 women) with chronic HIV infection and 18 HIV-uninfected controls (9 men and 9 women) from Thailand. Following enrollment, participants began combination antiretroviral therapy and were evaluated for expression of these markers after 48 weeks.
Methods: Plasma and CSF levels of 19 soluble biomarkers (IFN-gamma TNF alpha, TN F-RII, IL-1 alpha, IL-1 beta, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-15, MCP-1, t-Tau, IP-10, neopterin, IFN alpha, I-FABP, and sCD14) were measured using either a multiparameter or standard ELISA assay.
Results: Prior to combination antiretroviral therapy, women with impaired cognition had elevated levels of neopterin and TNF-RII compared with women with normal cognition in both the plasma and CSF; however, levels did not differ between cognitively impaired or normal men. In a secondary outcome-hypothesis generating analysis, sex differences were also pronounced in plasma levels of MCP-1, IL-10, I-FABP, and sCD14 in response to treatment. Neopterin, IP-10, TNF alpha, IFN alpha, MCP-1, IL-8, I-FABP, and sCD14 plasma levels remained elevated following 48 weeks of therapy in both sexes compared with uninfected controls.
Conclusion: We provide evidence of sustained immune activation after 48 weeks of treatment and identify possible sex differences in biomarkers previously linked to cognitive impairment, chronic inflammation, and gut integrity that may contribute to immunological differences between sexes in relationship to disease progression and response to therapy. Copyright (C) 2016 Wolters Kluwer Health, Inc. All rights reserved.
C1 [Krebs, Shelly J.; Slike, Bonnie M.; Jagodzinski, Linda; Ananworanich, Jintanat; Marovich, Mary A.] US Mil HIV Res Program, 503 Robert Grant Ave, Silver Spring, MD 20910 USA.
[Krebs, Shelly J.; Slike, Bonnie M.; Ananworanich, Jintanat] Henry M Jackson Fdn Adv Mil Med, Bethesda, MD USA.
[Sithinamsuwan, Pasiri] Phramongkutklao Hosp, Bangkok, Thailand.
[Allen, Isabel E.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA.
[Chalermchai, Thep; Tipsuk, Somporn; Phanuphak, Nittaya; Ananworanich, Jintanat] SEARCH, Thai Red Cross AIDS Res Ctr, Bangkok, Thailand.
[Kim, Jerome H.] Int Vaccine Inst, Seoul, South Korea.
[Ananworanich, Jintanat] Chulalongkorn Univ, Bangkok, Thailand.
[Marovich, Mary A.] NIH, Vaccine Res & Dev Sect, Div Aids, Bldg 10, Bethesda, MD 20892 USA.
[Valcour, Victor G.] Univ Calif San Francisco, Dept Neurol, Memory & Aging Ctr, San Francisco, CA USA.
RP Krebs, SJ (reprint author), US Mil HIV Res Program, 503 Robert Grant Ave, Silver Spring, MD 20910 USA.
EM skrebs@hivresearch.org
FU NIH [R01NS061696]; Henry M. Jackson Foundation for the Advancement of
Military Medicine, Inc. [W81XWH-11-2-0174]; US Department of Defense
[W81XWH-11-2-0174]
FX The authors thank the SEARCH 011 Study Group volunteers for their
participation, and the physicians who cared for the volunteers. The
SEARCH 011 Study group includes Nitiya Chomchey, Somprartthana
Rattanamanee, James L. K. Fletcher, Duanghathai Sutthichom, and Pairoa
Praihirunkit from SEARCH/TRCARC; Nijasri Charnnarong and Sukalaya
Lerdlum from Chulalongkorn University; Yotin Chinvarun from
Phramongkutklao Medical Center; Mark de Souza, Alexandra Schuetz, and
Rapee Trichavaroj from the Armed Forces Research Institute of Medical
Sciences; Supunee Jirajariyavej from Taksin Hospital; Elijah Mun,
Stephanie Chiao, Akash Desai, Edgar Busovaca, Nicholas Hutchings, Collin
Adams, Katherine Clifford, and Lauren Wendelken from UCSF. The authors
also thank Matthew Creegan and Roger Faubel for technical support and
Michael Eller for critical review of this manuscript. The views
expressed are those of the authors and should not be construed to
represent the positions of the US Army or the Department of Defense.
This work was supported by R01NS061696 (NIH) and a cooperative agreement
(W81XWH-11-2-0174) between the Henry M. Jackson Foundation for the
Advancement of Military Medicine, Inc. and the US Department of Defense.
NR 41
TC 1
Z9 1
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0269-9370
EI 1473-5571
J9 AIDS
JI Aids
PD JUN 19
PY 2016
VL 30
IS 10
BP 1533
EP 1542
DI 10.1097/QAD.0000000000001096
PG 10
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA DN9SD
UT WOS:000377419500004
PM 26990631
ER
PT J
AU Yanik, EL
Katki, HA
Engels, EA
AF Yanik, Elizabeth L.
Katki, Hormuzd A.
Engels, Eric A.
TI Cancer risk among the HIV-infected elderly in the United States
SO AIDS
LA English
DT Article
DE aging; cancer; epidemiology; HIV
ID ANTIRETROVIRAL THERAPY; LUNG-CANCER; INDIVIDUALS; PEOPLE; AIDS;
IMMUNODEFICIENCY; METAANALYSIS; SMOKING; COHORT
AB Objective: HIV-infected people and elderly people have higher cancer risk, but the combined effects of aging and HIV are not well described. We aimed to evaluate the magnitude of cancer risk in the HIV-infected elderly population.
Design: We conducted a case-cohort study including a 5% sample of U.S. Medicare enrollees and all cancer cases aged at least 65 in linked cancer registries.
Methods: HIV was identified through Medicare claims. Among the HIV-infected, absolute cancer risk was calculated accounting for the competing risk of death. Associations between HIV and cancer were estimated with weighted Cox regression adjusting for demographic characteristics.
Results: Among 469 954 people in the 5% sample, 0.08% had an HIV diagnosis. Overall, 825 776 cancer cases were identified in cancer registries. Over 5 years, 10.1% of the HIV-infected elderly developed cancer, the most common diagnoses comprising lung (5-year cumulative incidence=2.2%), prostate (2.7%, among men), and colorectal cancer (0.9%), and non-Hodgkin lymphoma (0.8%). HIV was strongly associated with incidence of Kaposi sarcoma [adjusted hazard ratio (aHR)=94.4, 95% confidence interval (95%CI)=54.6-1631, anal cancer (aHR=34.2, 95%CI=23.9-49.0) and Hodgkin lymphoma (aH R=6.3, 95%CI=2.8-14.3). HIV was also associated with incidence of liver cancer, non-Hodgkin lymphoma and lung cancer (aHR=3.4, 2.6, and 1.6, respectively).
Conclusion: In the elderly, HIV infection is associated with higher risk for many cancers, although some associations were weaker than expected, perhaps reflecting effects of non-HIV pathways on cancer development. Due to the effects of HIV and aging, the HIV-infected elderly have a sizeable absolute risk, highlighting a need for cancer prevention. Copyright (C) 2016 Wolters Kluwer Health, Inc. All rights reserved.
C1 [Yanik, Elizabeth L.; Katki, Hormuzd A.; Engels, Eric A.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
RP Yanik, EL (reprint author), NCI, 9609 Med Ctr Dr,Rm 6E-216, Bethesda, MD 20892 USA.
EM elizabeth.yanik@nih.gov
OI Yanik, Elizabeth/0000-0002-5835-0201
FU National Cancer Institute at the National Institutes of Health; Office
of AIDS Research at the National Institutes of Health
FX E.L.Y., H.A.K., and E.A.E. were supported by the Intramural Research
Program of the National Cancer Institute at the National Institutes of
Health. E.L.Y. was also supported by an Intramural AIDS Research
Fellowship Award from the Office of AIDS Research at the National
Institutes of Health
NR 23
TC 7
Z9 7
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0269-9370
EI 1473-5571
J9 AIDS
JI Aids
PD JUN 19
PY 2016
VL 30
IS 10
BP 1663
EP 1668
DI 10.1097/QAD.0000000000001077
PG 6
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA DN9SD
UT WOS:000377419500016
PM 26950314
ER
PT J
AU Arbore, G
West, EE
Spolski, R
Robertson, AAB
Klos, A
Rheinheimer, C
Dutow, P
Woodruff, TM
Yu, ZX
O'Neill, LA
Coll, RC
Sher, A
Leonard, WJ
Kohl, J
Monk, P
Cooper, MA
Arno, M
Afzali, B
Lachmann, HJ
Cope, AP
Mayer-Barber, KD
Kemper, C
AF Arbore, Giuseppina
West, Erin E.
Spolski, Rosanne
Robertson, Avril A. B.
Klos, Andreas
Rheinheimer, Claudia
Dutow, Pavel
Woodruff, Trent M.
Yu, Zu Xi
O'Neill, Luke A.
Coll, Rebecca C.
Sher, Alan
Leonard, Warren J.
Koehl, Jorg
Monk, Pete
Cooper, Matthew A.
Arno, Matthew
Afzali, Behdad
Lachmann, Helen J.
Cope, Andrew P.
Mayer-Barber, Katrin D.
Kemper, Claudia
TI T helper 1 immunity requires complement-driven NLRP3 inflammasome
activity in CD4(+) T cells
SO SCIENCE
LA English
DT Article
ID INNATE LYMPHOID-CELLS; C5A RECEPTOR CD88; INTESTINAL INFLAMMATION;
IFN-GAMMA; DIFFERENTIATION; ACTIVATION; C5L2; CYTOKINE; DISEASE;
ANTAGONISTS
C1 [Arbore, Giuseppina; Afzali, Behdad; Kemper, Claudia] Kings Coll London, Div Transplant Immunol & Mucosal Biol, MRC Ctr Transplantat, London SE1 9RT, England.
[West, Erin E.; Spolski, Rosanne; Leonard, Warren J.; Kemper, Claudia] NHLBI, Lab Mol Immunol, Bldg 10, Bethesda, MD 20892 USA.
[Robertson, Avril A. B.; Woodruff, Trent M.; Coll, Rebecca C.; Cooper, Matthew A.] Univ Queensland, Inst Mol Biosci, Brisbane, Qld 4072, Australia.
[Klos, Andreas; Rheinheimer, Claudia; Dutow, Pavel] Hannover Med Sch, Inst Med Microbiol & Hosp Epidemiol, D-30625 Hannover, Germany.
[Yu, Zu Xi] NHLBI, Pathol Core, Bldg 10, Bethesda, MD 20892 USA.
[O'Neill, Luke A.] Univ Dublin Trinity Coll, Sch Biochem & Immunol, Dublin 2, Ireland.
[Sher, Alan] NIAID, Parasit Dis Lab, Bethesda, MD 20892 USA.
[Koehl, Jorg] Med Univ Lubeck, Inst Syst Inflammat Res, D-23538 Lubeck, Germany.
[Koehl, Jorg] Cincinnati Childrens Hosp Med Ctr, Div Immunobiol, Cincinnati, OH 45229 USA.
[Koehl, Jorg] Univ Cincinnati, Coll Med, Cincinnati, OH USA.
[Monk, Pete] Univ Sheffield, Dept Infect & Immun, Sheffield S10 2RX, S Yorkshire, England.
[Arno, Matthew] Kings Coll London, Fac Life Sci & Med, Genom Ctr, London SE1 9NH, England.
[Afzali, Behdad] NIAMSD, Lymphocyte Cell Biol Sect, Mol Immunol & Inflammat Branch, Bethesda, MD 20892 USA.
[Lachmann, Helen J.] UCL, Div Med, UK Natl Amyloidosis Ctr, Royal Free Campus, London NW3 2PF, England.
[Cope, Andrew P.] Kings Coll London, Div Immunol Infect & Inflammatory Dis, Acad Dept Rheumatol, London SE1 1UL, England.
[Mayer-Barber, Katrin D.] NIAID, Lab Clin Infect Dis, Inflammat & Innate Immun Unit, 9000 Rockville Pike, Bethesda, MD 20892 USA.
RP Kemper, C (reprint author), Kings Coll London, Div Transplant Immunol & Mucosal Biol, MRC Ctr Transplantat, London SE1 9RT, England.; Kemper, C (reprint author), NHLBI, Lab Mol Immunol, Bldg 10, Bethesda, MD 20892 USA.
EM claudia.kemper@kcl.ac.uk
RI Monk, Peter/C-6155-2008; Woodruff, Trent/B-4861-2009; Coll,
Rebecca/J-2124-2014; Robertson, Avril/A-4043-2012; Koehl,
Joerg/C-8531-2011;
OI Monk, Peter/0000-0003-4637-3059; Woodruff, Trent/0000-0003-1382-911X;
Coll, Rebecca/0000-0002-7359-6023; Robertson, Avril/0000-0002-9652-8357;
Koehl, Joerg/0000-0003-1121-3178; Cooper, Matthew/0000-0003-3147-3460
FU British Heart Foundation [PG/09/018/25279]; Intramural NIH HHS [Z99
AI999999, ZIA AI001207-01]; Medical Research Council [MR/J006742/1];
Wellcome Trust
NR 59
TC 20
Z9 20
U1 0
U2 3
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 0036-8075
EI 1095-9203
J9 SCIENCE
JI Science
PD JUN 17
PY 2016
VL 352
IS 6292
AR aad1210
DI 10.1126/science.aad1210
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DO7PV
UT WOS:000377975400040
PM 27313051
ER
PT J
AU Vemu, A
Atherton, J
Spector, JO
Szyk, A
Moores, CA
Roll-Mecak, A
AF Vemu, Annapurna
Atherton, Joseph
Spector, Jeffrey O.
Szyk, Agnieszka
Moores, Carolyn A.
Roll-Mecak, Antonina
TI Structure and Dynamics of Single-isoform Recombinant Neuronal Human
Tubulin
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID MICROTUBULE PLUS-END; ALPHA-BETA-TUBULIN; IN-VITRO; ELECTRON
CRYOMICROSCOPY; GTP HYDROLYSIS; RESOLUTION; INSTABILITY; MICROSCOPY;
RECONSTRUCTIONS; ISOTYPES
AB Microtubules are polymers that cycle stochastically between polymerization and depolymerization, i.e. they exhibit "dynamic instability." This behavior is crucial for cell division, motility, and differentiation. Although studies in the last decade have made fundamental breakthroughs in our understanding of how cellular effectors modulate microtubule dynamics, analysis of the relationship between tubulin sequence, structure, and dynamics has been held back by a lack of dynamics measurements with and structural characterization of homogeneous isotypically pure engineered tubulin. Here, we report for the first time the cryo-EM structure and in vitro dynamics parameters of recombinant isotypically pure human tubulin. alpha 1A/beta III is a purely neuronal tubulin isoform. The 4.2-angstrom structure of post-translationally unmodified human alpha 1A/beta III microtubules shows overall similarity to that of heterogeneous brain microtubules, but it is distinguished by subtle differences at polymerization interfaces, which are hot spots for sequence divergence between tubulin isoforms. In vitro dynamics assays show that, like mosaic brain microtubules, recombinant homogeneous microtubules undergo dynamic instability, but they polymerize slower and have fewer catastrophes. Interestingly, we find that epitaxial growth of alpha 1A/beta III microtubules from heterogeneous brain seeds is inefficient but can be fully rescued by incorporating as little as 5% of brain tubulin into the homogeneous alpha 1A/beta III lattice. Our study establishes a system to examine the structure and dynamics of mammalian microtubules with well defined tubulin species and is a first and necessary step toward uncovering how tubulin genetic and chemical diversity is exploited to modulate intrinsic microtubule dynamics.
C1 [Vemu, Annapurna; Spector, Jeffrey O.; Szyk, Agnieszka; Roll-Mecak, Antonina] NINDS, Cell Biol & Biophys Unit, Bethesda, MD 20892 USA.
[Roll-Mecak, Antonina] NHLBI, Ctr Biophys, NIH, Bethesda, MD 20892 USA.
[Atherton, Joseph; Moores, Carolyn A.] Univ London, Inst Struct & Mol Biol, Dept Biol Sci, Birkbeck Coll, London WC1E, England.
RP Moores, CA (reprint author), Birkbeck Coll, Inst Struct & Mol Biol, London WC1E 7HX, England.; Roll-Mecak, A (reprint author), NIH, Cell Biol & Biophys Unit, Porter Neurosci Res Ctr, Bldg 35,Rm 3B-203,35 Convent Dr,MSC 3700, Bethesda, MD 20892 USA.
EM c.moores@mail.cryst.bbk.ac.uk; Antonina@mail.nih.gov
FU Medical Research Council, United Kingdom; NINDS; NHLBI, National
Institutes of Health
FX This work was supported by grants from the Medical Research Council,
United Kingdom (to J. A. and C. A. M.), and by the Intramural Programs
of the NINDS and the NHLBI, National Institutes of Health (to A. V., J.
O. S., A. S. and A. R.-M.). The content is solely the responsibility of
the authors and does not necessarily represent the official views of the
National Institutes of Health.
NR 51
TC 1
Z9 1
U1 1
U2 2
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
EI 1083-351X
J9 J BIOL CHEM
JI J. Biol. Chem.
PD JUN 17
PY 2016
VL 291
IS 25
BP 12907
EP +
DI 10.1074/jbc.C116.731133
PG 12
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA DR2YT
UT WOS:000379770500002
PM 27129203
ER
PT J
AU Navarro, G
Aguinaga, D
Angelats, E
Medrano, M
Moreno, E
Mallol, J
Cortes, A
Canela, EI
Casado, V
McCormick, PJ
Lluis, C
Ferre, S
AF Navarro, Gemma
Aguinaga, David
Angelats, Edgar
Medrano, Mireia
Moreno, Estefania
Mallol, Josefa
Cortes, Antonio
Canela, Enric I.
Casado, Vicent
McCormick, Peter J.
Lluis, Carme
Ferre, Sergi
TI A Significant Role of the Truncated Ghrelin Receptor GHS-R1b in
Ghrelin-induced Signaling in Neurons
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID PROTEIN-COUPLED RECEPTORS; CELL-SURFACE EXPRESSION; ALLOSTERIC
INTERACTIONS; POLYPEPTIDE GHS-R1B; INSULIN-RELEASE; HETEROTETRAMER;
HETERODIMERS; ACTIVATION; ATTENUATE; PATHWAYS
AB The truncated non-signaling ghrelin receptor growth hormone secretagogue R1b (GHS-R1b) has been suggested to simply exert a dominant negative role in the trafficking and signaling of the full and functional ghrelin receptor GHS-R1a. Here we reveal a more complex modulatory role of GHS-R1b. Differential co-expression of GHS-R1a and GHS-R1b, both in HEK-293T cells and in striatal and hippocampal neurons in culture, demonstrates that GHS-R1b acts as a dual modulator of GHS-R1a function: low relative GHS-R1b expression potentiates and high relative GHS-R1b expression inhibits GHS-R1a function by facilitating GHS-R1a trafficking to the plasma membrane and by exerting a negative allosteric effect on GHS-R1a signaling, respectively. We found a preferential G(i/o) coupling of the GHS-R1a-GHS-R1b complex in HEK-293T cells and, unexpectedly, a preferential G(s/olf) coupling in both striatal and hippocampal neurons in culture. A dopamine D-1 receptor (D1R) antagonist blocked ghrelin-induced cAMP accumulation in striatal but not hippocampal neurons, indicating the involvement of D1R in the striatal GHS-R1a-G(s/olf) coupling. Experiments in HEK-293T cells demonstrated that D1R co-expression promotes a switch in GHS-R1a-G protein coupling from G(i/o) to G(s/olf), but only upon co-expression of GHS-R1b. Furthermore, resonance energy transfer experiments showed that D1R interacts with GHS-R1a, but only in the presence of GHS-R1b. Therefore, GHS-R1b not only determines the efficacy of ghrelin-induced GHS-R1a-mediated signaling but also determines the ability of GHS-R1a to form oligomeric complexes with other receptors, promoting profound qualitative changes in ghrelin-induced signaling.
C1 [Navarro, Gemma; Aguinaga, David; Angelats, Edgar; Medrano, Mireia; Moreno, Estefania; Mallol, Josefa; Cortes, Antonio; Canela, Enric I.; Casado, Vicent; Lluis, Carme] Univ Barcelona, Fac Biol, Dept Biochem & Mol Biol, Diagonal 645, E-08028 Barcelona, Spain.
[Navarro, Gemma; Aguinaga, David; Angelats, Edgar; Medrano, Mireia; Moreno, Estefania; Mallol, Josefa; Cortes, Antonio; Canela, Enric I.; Casado, Vicent; Lluis, Carme] Ctr Invest Biomed Red Enfermedades Neurodegenerat, Barcelona 08028, Spain.
[McCormick, Peter J.] Univ East Anglia, Sch Pharm, Norwich Res Pk, Norwich NR4 7TJ, Norfolk, England.
[Ferre, Sergi] NIDA, Integrat Neurobiol Sect, Intramural Res Program, Baltimore, MD 21224 USA.
RP Navarro, G (reprint author), Univ Barcelona, Fac Biol, Dept Biochem & Mol Biol, Diagonal 645, E-08028 Barcelona, Spain.; Ferre, S (reprint author), NIDA, Integrat Neurobiol Sect, Intramural Res Program, NIH, Triad Technol Bldg,333 Cassell Dr, Baltimore, MD 21224 USA.
EM dimartts@hotmail.com; sferre@intra.nida.nih.gov
RI Ferre, Sergi/K-6115-2014; Canela, Enric I./M-8726-2013
OI Ferre, Sergi/0000-0002-1747-1779; Canela, Enric I./0000-0003-4992-7440
FU Spanish Ministerio de Ciencia y Tecnologia [SAF2011-23813]; government
of Catalonia [2014-SGR-1236]; Centro de Investigacion Biomedica en Red
sobre Enfermedades Neurodegenerativas Grant [CB06/05/0064]; National
Institute on Drug Abuse; Ramon y Cajal fellowship
FX This work was supported by Spanish Ministerio de Ciencia y Tecnologia
Grant SAF2011-23813, government of Catalonia Grant 2014-SGR-1236, Centro
de Investigacion Biomedica en Red sobre Enfermedades Neurodegenerativas
Grant CB06/05/0064, and intramural funds of the National Institute on
Drug Abuse. The authors declare that they have no conflicts of interest
with the contents of this article.; Supported by a Ramon y Cajal
fellowship.
NR 29
TC 1
Z9 1
U1 2
U2 5
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
EI 1083-351X
J9 J BIOL CHEM
JI J. Biol. Chem.
PD JUN 17
PY 2016
VL 291
IS 25
BP 13048
EP 13062
DI 10.1074/jbc.M116.715144
PG 15
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA DR2YT
UT WOS:000379770500014
PM 27129257
ER
PT J
AU Lu, JX
Bayro, MJ
Tycko, R
AF Lu, Jun-Xia
Bayro, Marvin J.
Tycko, Robert
TI Major Variations in HIV-1 Capsid Assembly Morphologies Involve Minor
Variations in Molecular Structures of Structurally Ordered Protein
Segments
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; SOLID-STATE NMR;
NUCLEAR-MAGNETIC-RESONANCE; ANGLE-SPINNING NMR; CHEMICAL-SHIFTS; GAG
POLYPROTEIN; TERMINAL DOMAIN; DIMERIZATION DOMAIN; CRYSTAL-STRUCTURE;
LATTICE FORMATION
AB We present the results of solid state nuclear magnetic resonance (NMR) experiments on HIV-1 capsid protein (CA) assemblies with three different morphologies, namely wild-type CA (WT-CA) tubes with 35-60 nm diameters, planar sheets formed by the Arg(18)-Leu mutant (R18L-CA), and R18L-CA spheres with 20-100 nm diameters. The experiments are intended to elucidate molecular structural variations that underlie these variations in CA assembly morphology. We find that multidimensional solid state NMR spectra of N-15, C-13-labeled CA assemblies are remarkably similar for the three morphologies, with only small differences in N-15 and C-13 chemical shifts, no significant differences in NMR line widths, and few differences in the number of detectable NMR cross-peaks. Thus, the pronounced differences in morphology do not involve major differences in the conformations and identities of structurally ordered protein segments. Instead, morphological variations are attributable to variations in conformational distributions within disordered segments, which do not contribute to the solid state NMR spectra. Variations in solid state NMR signals from certain amino acid side chains are also observed, suggesting differences in the intermolecular dimerization interface between curved and planar CA lattices, as well as possible differences in intramolecular helix-helix packing.
C1 [Lu, Jun-Xia; Bayro, Marvin J.; Tycko, Robert] NIDKK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
[Lu, Jun-Xia] ShanghaiTech Univ, Sch Life Sci & Technol, 100 Haike Rd, Shanghai 201210, Peoples R China.
RP Tycko, R (reprint author), Bldg 5,Rm 112, Bethesda, MD 20892 USA.
EM robertty@mail.nih.gov
RI Bayro, Marvin/Q-4643-2016
OI Bayro, Marvin/0000-0003-1482-9381
FU NIDDK, National Institutes of Health [DK075032]; National Institutes of
Health
FX This work was supported by the Intramural Research Program of the NIDDK,
National Institutes of Health, under project DK075032, and by the
Intramural AIDS Targeted Antiviral Program of the National Institutes of
Health. The content is solely the responsibility of the authors and does
not necessarily represent the official views of the National Institutes
of Health. The authors declare that they have no conflicts of interest
with the contents of this article.
NR 58
TC 3
Z9 3
U1 1
U2 7
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
EI 1083-351X
J9 J BIOL CHEM
JI J. Biol. Chem.
PD JUN 17
PY 2016
VL 291
IS 25
BP 13098
EP +
DI 10.1074/jbc.M116.720557
PG 30
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA DR2YT
UT WOS:000379770500018
PM 27129282
ER
PT J
AU Celik, H
Bulut, G
Han, J
Graham, GT
Minas, TZ
Conn, EJ
Hong, SH
Pauly, GT
Hayran, M
Li, X
Ozdemirli, M
Ayhan, A
Rudek, MA
Toretsky, JA
Uren, A
AF Celik, Haydar
Bulut, Gulay
Han, Jenny
Graham, Garrett T.
Minas, Tsion Z.
Conn, Erin J.
Hong, Sung-Hyeok
Pauly, Gary T.
Hayran, Mutlu
Li, Xin
Ozdemirli, Metin
Ayhan, Ayse
Rudek, Michelle A.
Toretsky, Jeffrey A.
Uren, Aykut
TI Ezrin Inhibition Up-regulates Stress Response Gene Expression
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID METASTATIC PHENOTYPE; ERM PROTEINS; OSTEOSARCOMA METASTASIS;
ENDOPLASMIC-RETICULUM; CARCINOMA-CELLS; MURINE MODEL; LINKER EZRIN;
CANCER; METABOLISM; PATHWAY
AB Ezrin is a member of the ERM (ezrin/radixin/moesin) family of proteins that links cortical cytoskeleton to the plasma membrane. High expression of ezrin correlates with poor prognosis and metastasis in osteosarcoma. In this study, to uncover specific cellular responses evoked by ezrin inhibition that can be used as a specific pharmacodynamic marker(s), we profiled global gene expression in osteosarcoma cells after treatment with small molecule ezrin inhibitors, NSC305787 and NSC668394. We identified and validated several up-regulated integrated stress response genes including PTGS2, ATF3, DDIT3, DDIT4, TRIB3, and ATF4 as novel ezrin-regulated transcripts. Analysis of transcriptional response in skin and peripheral blood mononuclear cells from NSC305787-treated mice compared with a control group revealed that, among those genes, the stress gene DDIT4/REDD1 may be used as a surrogate pharmacodynamic marker of ezrin inhibitor compound activity. In addition, we validated the anti-metastatic effects of NSC305787 in reducing the incidence of lung metastasis in a genetically engineered mouse model of osteosarcoma and evaluated the pharmacokinetics of NSC305787 and NSC668394 in mice. In conclusion, our findings suggest that cytoplasmic ezrin, previously considered a dormant and inactive protein, has important functions in regulating gene expression that may result in down-regulation of stress response genes.
C1 [Celik, Haydar; Bulut, Gulay; Han, Jenny; Graham, Garrett T.; Minas, Tsion Z.; Conn, Erin J.; Hong, Sung-Hyeok; Toretsky, Jeffrey A.; Uren, Aykut] Georgetown Univ, Med Ctr, Dept Oncol, Washington, DC 20007 USA.
[Ozdemirli, Metin] Georgetown Univ, Med Ctr, Dept Pathol, Washington, DC 20007 USA.
[Bulut, Gulay] Bahcesehir Univ, Fac Engn & Nat Sci, Dept Mol Biol & Genet, TR-34349 Istanbul, Turkey.
[Pauly, Gary T.] NCI, Biol Chem Lab, Ctr Canc Res, NIH, Frederick, MD 21702 USA.
[Hayran, Mutlu] Hacettepe Univ, Inst Canc, Dept Prevent Oncol, TR-06800 Ankara, Turkey.
[Li, Xin] Georgetown Univ, Dept Biostat Bioinformat & Biomath, Washington, DC 20057 USA.
[Ayhan, Ayse] Seirei Mikatahara Hosp, Dept Pathol, Hamamatsu, Shizuoka, Japan.
[Ayhan, Ayse] Hamamatsu Univ Sch Med, Hamamatsu, Shizuoka, Japan.
[Ayhan, Ayse] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21218 USA.
[Rudek, Michelle A.] Johns Hopkins Univ, Sch Med, Div Clin Pharmacol, Dept Oncol, Baltimore, MD 21218 USA.
[Rudek, Michelle A.] Johns Hopkins Univ, Sch Med, Div Clin Pharmacol, Dept Med, Baltimore, MD 21218 USA.
Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21218 USA.
RP Uren, A (reprint author), Georgetown Univ, Med Ctr, Dept Oncol, Dept Biochem & Mol & Cellular Biol,NRB, 3970 Reservoir Rd NW,Rm E312, Washington, DC 20057 USA.
EM au26@georgetown.edu
OI Graham, Garrett/0000-0002-1097-0962
FU National Cancer Institute [P30CA51008]
FX We thank the Animal Models Shared Resource, Histopathology & Tissue
Shared Resource and the Genomics & Epigenomics Shared Resource at the
Lombardi Comprehensive Cancer Center (Georgetown University), which are
supported by a grant P30CA51008 from the National Cancer Institute. We
thank Dr. Chand Khanna from National Cancer Institute (NCI/NIH,
Bethesda, MD) for providing human MG63.3 osteosarcoma and mouse K7M2
osteosarcoma cell lines. We thank Dr. Douglas H. Thamm (Colorado State
University, Fort Collins, CO) for providing MCKOS, SKKOS and CSKOS
canine osteosarcoma cell lines. We thank Dr. Stuart H. Orkin and Dr.
Katherine A. Janeway (Harvard Medical School, Boston, MA) for providing
mice to generate the Osx-Cre +
p53fl/flpRBfl/fl transgenic mouse model of
osteosarcoma and helpful discussion. We thank the Brandon Carrington Lee
Foundation and Children's Cancer Foundation for continuous support of
our research program.
NR 48
TC 0
Z9 0
U1 2
U2 5
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
EI 1083-351X
J9 J BIOL CHEM
JI J. Biol. Chem.
PD JUN 17
PY 2016
VL 291
IS 25
BP 13257
EP 13270
DI 10.1074/jbc.M116.718189
PG 14
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA DR2YT
UT WOS:000379770500030
PM 27137931
ER
PT J
AU Castelnuovo, B
Kiragga, A
Mubiru, F
Kambugu, A
Kamya, M
Reynolds, SJ
AF Castelnuovo, Barbara
Kiragga, Agnes
Mubiru, Frank
Kambugu, Andrew
Kamya, Moses
Reynolds, Steven J.
TI First-line antiretroviral therapy durability in a 10-year cohort of
naive adults started on treatment in Uganda
SO JOURNAL OF THE INTERNATIONAL AIDS SOCIETY
LA English
DT Article
DE antiretroviral treatment; treatments failure; long term outcomes
ID RESOURCE-LIMITED SETTINGS; PRESIDENTS EMERGENCY PLAN; HIV
DRUG-RESISTANCE; TREATMENT FAILURE; VIRAL FAILURE; SOUTH-AFRICA; AIDS
RELIEF; PREDICTORS; INFECTION; ADHERENCE
AB Introduction: The majority of studies from resource-limited settings only report short-term virological outcomes of patients on antiretroviral treatment (ART). We aim to describe the long-term durability of first-line ART and identify factors associated with long-term virological outcomes.
Methods: At the Infectious Diseases Institute in Kampala, Uganda, 559 adult patients starting ART in 2004 were enrolled into a research cohort and monitored with viral load (VL) testing every six months for 10 years. We report the proportion and cumulative probability of 1) achieving virologic suppression (at least one VL <400 copies/ml); 2) experiencing virologic failure in patients who achieved suppression (two consecutive VLs >1000 copies/ml or one VL >5000, for those without a subsequent one); 3) treatment failure (not attaining virologic suppression or experiencing virologic failure). We used Cox regression methods to determine the characteristics associated with treatment failure. We included gender, baseline age, WHO stage, body mass index, CD4 count, propensity score for initial ART regimen, VL, time-dependent CD4 count and adherence.
Results: Of the 559 patients enrolled, 472 (84.8%) had at least one VL (67 died, 13 were lost to follow-up, 4 transferred, 2 had no VL available); 73.6% started on d4T/3TC/nevirapine and 26.4% on AZT/3TC/efavirenz. Patients in the two groups had similar characteristics, except for the higher proportion of patients in WHO Stage 3/4 and higher VL in the efavirenz-based group. Four hundred thirty-nine (93%) patients achieved virologic suppression with a cumulative probability of 0.94 (confidence interval (CI): 0.92-0.96); 74/439 (16.9%) experienced virologic failure with a cumulative probability of 0.18 (CI: 0.15-0.22). In the multivariate analysis, initial d4T/3TC/ nevirapine regimen (hazard ratio (HR): 3.02; CI: 3.02 (1.66-5.44, p < 0.001)) and baseline VL >= 5 log10 copies/ml (HR: 2.29; CI: 1.29-4.04) were associated with treatment failures; patients of older age (HR: 0.87 per five-year increase; CI: 0.77-0.99), with adherence >95% (HR: 0.04; CI: 0.02-0.11) and with higher time-dependent CD4 count (HR: 0.94 per 50 cells/mu l increase; CI: 0.92-0.99, p < 0.001) were less likely to experience treatment failure.
Conclusions: The long-term virological outcomes from this cohort are promising and comparable to those from research-rich settings. Our results provide further evidence that efavirenz is associated with better virological outcomes.
C1 [Castelnuovo, Barbara; Kiragga, Agnes; Mubiru, Frank; Kambugu, Andrew] Makerere Univ, Infect Dis Inst, Kampala, Uganda.
[Kamya, Moses] Makerere Univ, Sch Med, Kampala, Uganda.
[Reynolds, Steven J.] NIAID, Div Intramural Res, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Reynolds, Steven J.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA.
RP Castelnuovo, B (reprint author), Mulago Hosp, Infect Dis Inst, Kampala, Uganda.
EM bcastelnuovo@idi.co.ug
FU Division of Intramural Research, National Institute of Allergy and
Infectious Disease, National Institutes of Health
FX This study was supported in part (SJR) by the Division of Intramural
Research, National Institute of Allergy and Infectious Disease, National
Institutes of Health.
NR 37
TC 0
Z9 0
U1 1
U2 1
PU INT AIDS SOCIETY
PI GENEVA
PA AVENUE DE FRANCE 23, GENEVA, 1202, SWITZERLAND
SN 1758-2652
J9 J INT AIDS SOC
JI J. Int. AIDS Soc.
PD JUN 17
PY 2016
VL 19
AR 20773
DI 10.7448/IAS.19.1.20773
PG 6
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA DP1AW
UT WOS:000378223600001
PM 27319742
ER
PT J
AU Carlier, J
Scheidweiler, KB
Wohlfarth, A
Salmeron, BD
Baumann, MH
Huestis, MA
AF Carlier, Jeremy
Scheidweiler, Karl B.
Wohlfarth, Ariane
Salmeron, Bonita D.
Baumann, Michael H.
Huestis, Marilyn A.
TI Quantification of
[1-(5-fluoropentyl)-1H-indol-3-yl](naphthalene-1-yl)methanone (AM-2201)
and 13 metabolites in human and rat plasma by liquid
chromatography-tandem mass spectrometry
SO JOURNAL OF CHROMATOGRAPHY A
LA English
DT Article
DE AM-2201; Synthetic cannabinoid; Metabolites; Plasma; Liquid
chromatography-tandem mass spectrometry
ID SYNTHETIC CANNABINOIDS; HUMAN URINE; DRUGS; ABUSE; MS/MS
AB AM-2201 is a popular synthetic cannabinoid first synthesized in 2000. AM-2201 pharmacokinetic and pharmacodynamic data are scarce, requiring further investigation. We developed a sensitive method for quantifying AM-2201 and 13 metabolites in plasma to provide a tool to further metabolic, pharmacolcinetic and pharmacodynamic studies. Analysis was performed by liquid chromatography-tandem mass spectrometry. Chromatographic separation was performed by gradient elution on a biphenyl column with 0.1% formic acid in water/0.1% formic acid in acetonitrile:methanol 50:50 (v/v) mobile phase. Sample preparation (75 mu L) consisted of an enzymatic hydrolysis and a supported liquid extraction. The method was validated with human plasma with a 0.025 or 0.050-50 mu g/L, working range, and cross validated for rat plasma. Analytical recovery was 88.8-110.1% of target concentration, and intra- (n = 30) and inter-day (n = 30) imprecision <11.9% coefficient of variation. Method recoveries and matrix effects ranged from 58.4-84.4% and -62.1 to -15.6%, respectively. AM-2201 and metabolites were stable (+/- 20%) at room temperature for 24 h, at 4 degrees C for 72 h, and after three freeze-thaw cycles, and for 72 h in the autosampler after extraction. The method was developed for pharmacodynamic and pharmacokinetic studies with controlled administration in rats but is applicable for pre-clinical and clinical research and forensic investigations. Rat plasma specimen analysis following subcutaneous AM-2201 administration demonstrated the suitability of the method. AM-2201, JWH-018 N-(5-hydroxypentyl), and JWH-018 N-pentanoic acid concentrations were 4.8 +/- 1.0, 0.15 +/- 0.03, and 0.34 +/- 0.07 mu g/L, respectively, 8h after AM-2201 administration at 0.3 mg/kg (n = 5). Published by Elsevier B.V.
C1 [Carlier, Jeremy; Scheidweiler, Karl B.; Wohlfarth, Ariane; Huestis, Marilyn A.] NIDA, Clin Pharmacol & Therapeut Res Branch, Chem & Drug Metab Sect, Intramural Res Program,NIH, 251 Bayview Blvd Suite 200, Baltimore, MD 21224 USA.
[Salmeron, Bonita D.; Baumann, Michael H.] NIDA, Designer Drug Res Unit, Intramural Res Program, NIH, 333 Cassell Dr Suite 4400, Baltimore, MD 21224 USA.
[Wohlfarth, Ariane] Natl Board Forens Med, Dept Forens Genet & Forens Toxicol, Artillerigatan 12, SE-58758 Linkoping, Sweden.
[Wohlfarth, Ariane] Linkoping Univ, Dept Med & Hlth Sci, Div Drug Res, SE-58158 Linkoping, Sweden.
[Huestis, Marilyn A.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA.
RP Scheidweiler, KB (reprint author), NIDA, Clin Pharmacol & Therapeut Res Branch, Intramural Res Program, NIH, 251 Bayview Blvd Suite 200,Room BRC 05A729, Baltimore, MD 21224 USA.
EM KScheidweiler@intra.nida.nih.gov
FU Intramural Research Program of the National Institute on Drug Abuse
(NIDA), National Institutes of Health (NIH)
FX This study was supported by the Intramural Research Program of the
National Institute on Drug Abuse (NIDA), National Institutes of Health
(NIH).
NR 35
TC 0
Z9 0
U1 7
U2 17
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0021-9673
EI 1873-3778
J9 J CHROMATOGR A
JI J. Chromatogr. A
PD JUN 17
PY 2016
VL 1451
BP 97
EP 106
DI 10.1016/j.chroma.2016.05.020
PG 10
WC Biochemical Research Methods; Chemistry, Analytical
SC Biochemistry & Molecular Biology; Chemistry
GA DO4BD
UT WOS:000377725900012
PM 27208987
ER
PT J
AU Hinnebusch, AG
Ivanov, IP
Sonenberg, N
AF Hinnebusch, Alan G.
Ivanov, Ivaylo P.
Sonenberg, Nahum
TI Translational control by 5 '-untranslated regions of eukaryotic mRNAs
SO SCIENCE
LA English
DT Review
ID OPEN READING FRAMES; START CODON SELECTION; CAP-INDEPENDENT TRANSLATION;
INTEGRATED STRESS-RESPONSE; GENOME-WIDE ANALYSIS; SECONDARY STRUCTURE;
5' UTR; MODULATES AUTOREGULATION; NUCLEOTIDE RESOLUTION;
INITIATION-FACTORS
AB The eukaryotic 5' untranslated region (UTR) is critical for ribosome recruitment to the messenger RNA (mRNA) and start codon choice and plays a major role in the control of translation efficiency and shaping the cellular proteome. The ribosomal initiation complex is assembled on the mRNA via a cap-dependent or cap-independent mechanism. We describe various mechanisms controlling ribosome scanning and initiation codon selection by 5' upstream open reading frames, translation initiation factors, and primary and secondary structures of the 5' UTR, including particular sequence motifs. We also discuss translational control via phosphorylation of eukaryotic initiation factor 2, which is implicated in learning and memory, neurodegenerative diseases, and cancer.
C1 [Hinnebusch, Alan G.; Ivanov, Ivaylo P.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Grp Cell Regulat & Dev, NIH, Bethesda, MD USA.
[Sonenberg, Nahum] McGill Univ, Dept Biochem, Montreal, PQ H3A 1A3, Canada.
[Sonenberg, Nahum] McGill Univ, Goodman Canc Ctr, Montreal, PQ H3A 1A3, Canada.
RP Sonenberg, N (reprint author), McGill Univ, Dept Biochem, Montreal, PQ H3A 1A3, Canada.; Sonenberg, N (reprint author), McGill Univ, Goodman Canc Ctr, Montreal, PQ H3A 1A3, Canada.
EM nahum.sonenberg@mcgill.ca
NR 60
TC 18
Z9 18
U1 13
U2 35
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 0036-8075
EI 1095-9203
J9 SCIENCE
JI Science
PD JUN 17
PY 2016
VL 352
IS 6292
BP 1413
EP 1416
DI 10.1126/science.aad9868
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DO7PV
UT WOS:000377975400038
PM 27313038
ER
PT J
AU Bott, LC
Salomons, FA
Maric, D
Liu, YH
Merry, D
Fischbeck, KH
Dantuma, NP
AF Bott, Laura C.
Salomons, Florian A.
Maric, Dragan
Liu, Yuhong
Merry, Diane
Fischbeck, Kenneth H.
Dantuma, Nico P.
TI The polyglutamine-expanded androgen receptor responsible for spinal and
bulbar muscular atrophy inhibits the APC/C-Cdh1 ubiquitin ligase complex
SO SCIENTIFIC REPORTS
LA English
DT Article
ID ANAPHASE-PROMOTING COMPLEX/CYCLOSOME; TRANSGENIC MOUSE MODEL; PROTEASOME
SYSTEM; NEURODEGENERATIVE DISEASES; MOTOR-NEURONS; AXONAL GROWTH; CELLS;
MUSCLE; IMPAIRMENT; 5-ALPHA-DIHYDROTESTOSTERONE
AB Polyglutamine expansion in the androgen receptor (AR) causes spinal and bulbar muscular atrophy (SBMA), an X-linked neuromuscular disease that is fully manifest only in males. It has been suggested that proteins with expanded polyglutamine tracts impair ubiquitin-dependent proteolysis due to their propensity to aggregate, but recent studies indicate that the overall activity of the ubiquitin-proteasome system is preserved in SBMA models. Here we report that AR selectively interferes with the function of the ubiquitin ligase anaphase-promoting complex/cyclosome (APC/C), which, together with its substrate adaptor Cdh1, is critical for cell cycle arrest and neuronal architecture. We show that both wild-type and mutant AR physically interact with the APC/C-Cdh1 complex in a ligand-dependent fashion without being targeted for proteasomal degradation. Inhibition of APC/C-Cdh1 by mutant but not wild-type AR in PC12 cells results in enhanced neurite outgrowth which is typically followed by rapid neurite retraction and mitotic entry. Our data indicate a role of AR in neuronal differentiation through regulation of APC/C-Cdh1 and suggest abnormal cell cycle reactivation as a pathogenic mechanism in SBMA.
C1 [Bott, Laura C.; Salomons, Florian A.; Dantuma, Nico P.] Karolinska Inst, Dept Cell & Mol Biol, S-17177 Stockholm, Sweden.
[Bott, Laura C.; Fischbeck, Kenneth H.] Natl Inst Neurol Disorders & Stroke, Neurogenet Branch, Bethesda, MD 20892 USA.
[Maric, Dragan] Natl Inst Neurol Disorders & Stroke, Flow Cytometry Core Facil, Bethesda, MD 20892 USA.
[Liu, Yuhong; Merry, Diane] Thomas Jefferson Univ, Dept Biochem & Mol Biol, Philadelphia, PA 19107 USA.
[Bott, Laura C.] Northwestern Univ, Dept Mol Biosci, Rice Inst Biomed Res, Evanston, IL 60208 USA.
RP Dantuma, NP (reprint author), Karolinska Inst, Dept Cell & Mol Biol, S-17177 Stockholm, Sweden.
EM nico.dantuma@ki.se
FU Swedish Cancer Society; Swedish Research Council; intramural NINDS
research funds [1ZIA NS003037]; KI-NIH Graduate Partnership Program in
Neuroscience
FX We would like to thank Dr. Jacques Neefjes and Amilcar Flores-Morales
for providing reagents. This work was supported by the Swedish Cancer
Society (N.P.D.), the Swedish Research Council (N.P.D.), and intramural
NINDS research funds (1ZIA NS003037; K.H.F.). L.C.B. was supported by
the KI-NIH Graduate Partnership Program in Neuroscience.
NR 65
TC 0
Z9 0
U1 4
U2 5
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2045-2322
J9 SCI REP-UK
JI Sci Rep
PD JUN 17
PY 2016
VL 6
AR 27703
DI 10.1038/srep27703
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DO8NF
UT WOS:000378039600001
PM 27312068
ER
PT J
AU Myers, JM
Cooper, LT
Kem, DC
Stavrakis, S
Kosanke, SD
Shevach, EM
Fairweather, D
Stoner, JA
Cox, CJ
Cunningham, MW
AF Myers, Jennifer M.
Cooper, Leslie T.
Kem, David C.
Stavrakis, Stavros
Kosanke, Stanley D.
Shevach, Ethan M.
Fairweather, DeLisa
Stoner, Julie A.
Cox, Carol J.
Cunningham, Madeleine W.
TI Cardiac myosin-Th17 responses promote heart failure in human myocarditis
SO JCI INSIGHT
LA English
DT Article
ID REGULATORY T-CELLS; EXPERIMENTAL AUTOIMMUNE MYOCARDITIS;
GROWTH-FACTOR-BETA; COXSACKIEVIRUS B3-INDUCED MYOCARDITIS; ROR-GAMMA-T;
CYTOKINE GM-CSF; TH17 CELLS; DILATED CARDIOMYOPATHY; VIRAL MYOCARDITIS;
T(H)17 CELLS
AB In human myocarditis and its sequela dilated cardiomyopathy (DCM), the mechanisms and immune phenotype governing disease and subsequent heart failure are not known. Here, we identified a Th17 cell immunophenotype of human myocarditis/DCM with elevated CD4(+) IL17(+) T cells and Th17-promoting cytokines IL-6, TGF-beta, and IL-23 as well as GM-CSF-secreting CD4(+) T cells. The Th17 phenotype was linked with the effects of cardiac myosin on CD14(+) monocytes, TLR2, and heart failure. Persistent heart failure was associated with high percentages of IL-17-producing T cells and IL-17-promoting cytokines, and the myocarditis/DCM phenotype included significantly low percentages of FOXP3(+) Tregs, which may contribute to disease severity. We demonstrate a potentially novel mechanism in human myocarditis/DCM in which TLR2 peptide ligands from human cardiac myosin stimulated exaggerated Th17-related cytokines including TGF-beta, IL-6, and IL-23 from myocarditic CD14(+) monocytes in vitro, and an anti-TLR2 antibody abrogated the cytokine response. Our translational study explains how an immune phenotype may be initiated by cardiac myosin TLR ligand stimulation of monocytes to generate Th17-promoting cytokines and development of pathogenic Th17 cells in human myocarditis and heart failure, and provides a rationale for targeting IL-17A as a therapeutic option.
C1 [Myers, Jennifer M.; Cox, Carol J.; Cunningham, Madeleine W.] Univ Oklahoma, Hlth Sci Ctr, Dept Microbiol & Immunol, Oklahoma City, OK 73190 USA.
[Cooper, Leslie T.; Fairweather, DeLisa] Mayo Clin, Dept Cardiovasc Dis, Jacksonville, FL 32224 USA.
[Kem, David C.] Univ Oklahoma, Hlth Sci Ctr, Dept Med Endocrinol, Oklahoma City, OK USA.
[Stavrakis, Stavros] Univ Oklahoma, Hlth Sci Ctr, Med Cardiol, Oklahoma City, OK USA.
[Kosanke, Stanley D.] Univ Oklahoma, Hlth Sci Ctr, Pathol, Oklahoma City, OK USA.
[Shevach, Ethan M.] NIAID, Immunol Lab, NIH, Bldg 10, Bethesda, MD 20892 USA.
[Fairweather, DeLisa] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA.
[Stoner, Julie A.] Univ Oklahoma, Hlth Sci Ctr, Dept Biostat & Epidemiol, Oklahoma City, OK USA.
RP Cunningham, MW (reprint author), Univ Oklahoma, Hlth Sci Ctr, 975 NE 10th St, Oklahoma City, OK 73104 USA.
EM madeleine-cunningham@ouhsc.edu
NR 87
TC 1
Z9 1
U1 0
U2 0
PU AMER SOC CLINICAL INVESTIGATION INC
PI ANN ARBOR
PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA
SN 2379-3708
J9 JCI INSIGHT
JI JCI Insight
PD JUN 16
PY 2016
VL 1
IS 9
AR e85851
DI 10.1172/jci.insight.85851
PG 19
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA EB1LG
UT WOS:000387112700001
ER
PT J
AU Heuston, EF
AF Heuston, Elisabeth F.
TI The potential of a single enhancer
SO BLOOD
LA English
DT Editorial Material
ID C/EBP-ALPHA; MICE; AML
C1 [Heuston, Elisabeth F.] NIH, Bldg 10, Bethesda, MD 20892 USA.
RP Heuston, EF (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA.
NR 9
TC 0
Z9 0
U1 1
U2 1
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA
SN 0006-4971
EI 1528-0020
J9 BLOOD
JI Blood
PD JUN 16
PY 2016
VL 127
IS 24
BP 2943
EP 2944
DI 10.1182/blood-2016-03-706218
PG 2
WC Hematology
SC Hematology
GA DP2RG
UT WOS:000378337100002
PM 27313321
ER
PT J
AU Maxson, JE
Ries, RE
Wang, YC
Gerbing, RB
Kolb, EA
Thompson, SL
Auvil, JMG
Marra, MA
Ma, Y
Zong, ZS
Mungall, AJ
Moore, R
Long, W
Gesuwan, P
Davidsen, TM
Hermida, LC
Hughes, SB
Farrar, JE
Radich, JP
Smith, MA
Gerhard, DS
Gamis, AS
Alonzo, TA
Meshinchi, S
AF Maxson, Julia E.
Ries, Rhonda E.
Wang, Yi-Cheng
Gerbing, Robert B.
Kolb, E. Anders
Thompson, Sarah L.
Auvil, Jaime M. Guidry
Marra, Marco A.
Ma, Yussanne
Zong, Zusheng
Mungall, Andrew J.
Moore, Richard
Long, William
Gesuwan, Patee
Davidsen, Tanja M.
Hermida, Leandro C.
Hughes, Seamus B.
Farrar, Jason E.
Radich, Jerald P.
Smith, Malcolm A.
Gerhard, Daniela S.
Gamis, Alan S.
Alonzo, Todd A.
Meshinchi, Soheil
TI CSF3R mutations have a high degree of overlap with CEBPA mutations in
pediatric AML
SO BLOOD
LA English
DT Letter
ID COLONY-STIMULATING FACTOR; ACUTE MYELOID-LEUKEMIA; CHRONIC NEUTROPHILIC
LEUKEMIA; SEVERE CONGENITAL NEUTROPENIA; BINDING-PROTEIN-ALPHA; SRC
KINASE LYN; FACTOR-RECEPTOR; TRANSCRIPTION FACTOR; T618I MUTATION;
ATYPICAL CML
C1 [Maxson, Julia E.; Ries, Rhonda E.; Thompson, Sarah L.; Hughes, Seamus B.; Radich, Jerald P.; Meshinchi, Soheil] Fred Hutchinson Canc Res Ctr, Div Clin Res, 1124 Columbia St, Seattle, WA 98104 USA.
[Wang, Yi-Cheng; Gerbing, Robert B.; Gamis, Alan S.; Alonzo, Todd A.; Meshinchi, Soheil] Childrens Oncol Grp, Monrovia, CA USA.
[Kolb, E. Anders] Alfred I duPont Hosp Children, Nemours Ctr Canc & Blood Disorders, Wilmington, DE USA.
[Auvil, Jaime M. Guidry; Gesuwan, Patee; Davidsen, Tanja M.; Hermida, Leandro C.; Gerhard, Daniela S.] NCI, Off Canc Genom, Bethesda, MD 20892 USA.
[Marra, Marco A.; Ma, Yussanne; Zong, Zusheng; Mungall, Andrew J.; Moore, Richard; Long, William] British Columbia Canc Agcy, Canadas Michael Smith Genome Sci Ctr, Vancouver, BC V5Z 4E6, Canada.
[Farrar, Jason E.] Univ Arkansas Med Sci, Arkansas Childrens Hosp, Res Inst, Little Rock, AR 72205 USA.
[Farrar, Jason E.] Univ Arkansas Med Sci, Dept Pediat, Little Rock, AR 72205 USA.
[Smith, Malcolm A.] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA.
[Gamis, Alan S.] Childrens Mercy Hosp & Clin, Div Hematol Oncol Bone Marrow Transplantat, Kansas City, MO USA.
[Alonzo, Todd A.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA.
RP Meshinchi, S (reprint author), Fred Hutchinson Canc Res Ctr, 1100 Fairview Ave N,D5-380, Seattle, WA 98109 USA.
EM smeshinc@fredhutch.org
RI Marra, Marco/B-5987-2008
FU NCI NIH HHS [R01 CA114563, U10 CA180899]; NIH HHS [S10 OD020069]
NR 23
TC 6
Z9 6
U1 2
U2 3
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA
SN 0006-4971
EI 1528-0020
J9 BLOOD
JI Blood
PD JUN 16
PY 2016
VL 127
IS 24
BP 3094
EP +
DI 10.1182/blood-2016-04-709899
PG 5
WC Hematology
SC Hematology
GA DP2RG
UT WOS:000378337100024
PM 27143256
ER
PT J
AU Lin, BR
Le, DJ
Chen, YB
Wang, QW
Chung, DD
Frausto, RF
Croasdale, C
Yee, RW
Hejtmancik, FJ
Aldave, AJ
AF Lin, Benjamin R.
Le, Derek J.
Chen, Yabin
Wang, Qiwei
Chung, D. Doug
Frausto, Ricardo F.
Croasdale, Christopher
Yee, Richard W.
Hejtmancik, Fielding J.
Aldave, Anthony J.
TI Whole Exome Sequencing and Segregation Analysis Confirms That a Mutation
in COL17A1 Is the Cause of Epithelial Recurrent Erosion Dystrophy in a
Large Dominant Pedigree Previously Mapped to Chromosome 10q23-q24
SO PLOS ONE
LA English
DT Article
ID BEHNKE CORNEAL-DYSTROPHY; INDIVIDUAL PHENOTYPIC VARIANCES; GENE;
PREDICTION; EXCLUSION; COLLAGEN; FAMILY; CDB2; XVII
AB Purpose
To report identification of a COL17A1 mutation in a family with a corneal dystrophy previously mapped to chromosome 10q23-q24.
Methods
Whole-exome sequencing was performed on DNA samples from five affected family members and two unrelated, unaffected individuals. Identified variants were filtered for those that were: located in the linked interval on chromosome 10q23-q24; novel or rare (minor allele frequency <= 0.01); heterozygous; present in all affected individuals and not in controls; and present in genes that encode proteins expressed in human corneal epithelial cells (reads per kilobase per million >= 1). Sanger sequencing of identified variants (SNVs) was performed in additional family members. In silico analysis was used to predict the functional impact of non-synonymous variants.
Results
Three SNVs located in two genes were identified that met the filtering criteria: one rare synonymous c.3156C>T variant in the collagen, type XVII, alpha I (COL17A1) gene; and two rare variants, one synonymous and one missense, in the dynamin binding protein (DNMBP) gene. Sanger sequencing of additional family members determined that only the COL17A1 variant segregates with the affected phenotype. In silico analysis predicts that the missense variant in DNMBP would be tolerated.
Conclusions
The corneal dystrophy mapped to chromosome 10q23-q24 is associated with the c.3156C>T variant in COL17A1. As this variant has recently been identified in five other families with early onset recurrent corneal erosions, and has been shown in vitro to introduce a cryptic splice donor site, this dystrophy is likely caused by aberrant splicing of COL17A1 and should be classified as epithelial recurrent erosion dystrophy.
C1 [Lin, Benjamin R.; Le, Derek J.; Chung, D. Doug; Frausto, Ricardo F.; Aldave, Anthony J.] Univ Calif Los Angeles, David Geffen Sch Med, Stein Eye Inst, Los Angeles, CA 90095 USA.
[Chen, Yabin; Wang, Qiwei; Hejtmancik, Fielding J.] NEI, Ophthalm Genet & Visual Funct Branch, NIH, Bethesda, MD 20892 USA.
[Croasdale, Christopher] Davis Duehr Dean Clin, Madison, WI USA.
[Yee, Richard W.] Cross Ophthalmol Associates, Houston, TX USA.
RP Aldave, AJ (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Stein Eye Inst, Los Angeles, CA 90095 USA.
EM aldave@jsei.ucla.edu
FU National Eye Institute [R01EY022082, Z01EY000272]; National Institute of
Health [P30 EY000331]; Research to Prevent Blindness (Stein Eye
Institute)
FX The work was supported by the following: National Eye Institute Grants
R01EY022082 (A.J.A.) and Z01EY000272 (F.J.H.), https://nei.nih.gov/;
National Institute of Health grant P30 EY000331 (core grant to Stein Eye
Institute), http://www.nih.gov/; unrestricted grant from Research to
Prevent Blindness (Stein Eye Institute), no grant #,
https://www.rpbusa.org/rpb/?. The funders had no role in study design,
data collection and analysis, decision to publish, or preparation of the
manuscript.
NR 24
TC 0
Z9 0
U1 0
U2 0
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUN 16
PY 2016
VL 11
IS 6
AR e0157418
DI 10.1371/journal.pone.0157418
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DO8JO
UT WOS:000378029800069
PM 27309958
ER
PT J
AU Rosenberg, AZ
Palmer, M
Merlino, L
Troost, JP
Gasim, A
Bagnasco, S
Avila-Casado, C
Johnstone, D
Hodgin, JB
Conway, C
Gillespie, BW
Nast, CC
Barisoni, L
Hewitt, SM
AF Rosenberg, Avi Z.
Palmer, Matthew
Merlino, Lino
Troost, Jonathan P.
Gasim, Adil
Bagnasco, Serena
Avila-Casado, Carmen
Johnstone, Duncan
Hodgin, Jeffrey B.
Conway, Catherine
Gillespie, Brenda W.
Nast, Cynthia C.
Barisoni, Laura
Hewitt, Stephen M.
TI The Application of Digital Pathology to Improve Accuracy in Glomerular
Enumeration in Renal Biopsies
SO PLOS ONE
LA English
DT Article
ID VIRTUAL MICROSCOPY; NEPHROTIC SYNDROME; NETWORK NEPTUNE; IGA
NEPHROPATHY; CLASSIFICATION; DENSITY; REPRODUCIBILITY; MULTICENTER;
NEPHRITIS; DISEASE
AB Background
In renal biopsy reporting, quantitative measurements, such as glomerular number and percentage of globally sclerotic glomeruli, is central to diagnostic accuracy and prognosis. The aim of this study is to determine the number of glomeruli and percent globally sclerotic in renal biopsies by means of registration of serial tissue sections and manual enumeration, compared to the numbers in pathology reports from routine light microscopic assessment.
Design
We reviewed 277 biopsies from the Nephrotic Syndrome Study Network (NEPTUNE) digital pathology repository, enumerating 9,379 glomeruli by means of whole slide imaging. Glomerular number and the percentage of globally sclerotic glomeruli are values routinely recorded in the official renal biopsy pathology report from the 25 participating centers. Two general trends in reporting were noted: total number per biopsy or average number per level/section. Both of these approaches were assessed for their accuracy in comparison to the analogous numbers of annotated glomeruli on WSI.
Results
The number of glomeruli annotated was consistently higher than those reported (p<0.001); this difference was proportional to the number of glomeruli. In contrast, percent globally sclerotic were similar when calculated on total glomeruli, but greater in FSGS when calculated on average number of glomeruli (p<0.01). The difference in percent globally sclerotic between annotated and those recorded in pathology reports was significant when global sclerosis is greater than 40%.
Conclusions
Although glass slides were not available for direct comparison to whole slide image annotation, this study indicates that routine manual light microscopy assessment of number of glomeruli is inaccurate, and the magnitude of this error is proportional to the total number of glomeruli.
C1 [Rosenberg, Avi Z.] Childrens Natl Med Ctr, Dept Pathol, Washington, DC 20010 USA.
[Rosenberg, Avi Z.] NIDDK, NIH, Bethesda, MD 20892 USA.
[Palmer, Matthew] Univ Penn, Dept Pathol, Philadelphia, PA 19104 USA.
[Merlino, Lino; Barisoni, Laura] Univ Miami, Dept Pathol, Miami, FL USA.
[Troost, Jonathan P.] Univ Michigan, Dept Pediat, Div Pediat Nephrol, Ann Arbor, MI 48109 USA.
[Gasim, Adil] Univ N Carolina, Dept Pathol, Chapel Hill, NC USA.
[Bagnasco, Serena] Johns Hopkins Sch Med, Dept Pathol, Baltimore, MD USA.
[Avila-Casado, Carmen] Toronto Gen Hosp, Dept Pathol, Toronto, ON, Canada.
[Johnstone, Duncan] Temple Univ, Dept Med, Sect Nephrol Hypertens & Kidney Transplantat, Philadelphia, PA 19122 USA.
[Hodgin, Jeffrey B.] Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA.
[Conway, Catherine; Hewitt, Stephen M.] NCI, Pathol Lab, Ctr Canc Res, NIH, Bldg 10, Bethesda, MD 20892 USA.
[Gillespie, Brenda W.] Univ Michigan, Sch Publ Hlth, Dept Biostat, Ann Arbor, MI 48109 USA.
[Nast, Cynthia C.] Cedars Sinai Med Ctr, Dept Pathol, Los Angeles, CA 90048 USA.
RP Hewitt, SM (reprint author), NCI, Pathol Lab, Ctr Canc Res, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM genejock@helix.nih.gov
FU Office of Rare Diseases Research, NCATS [U54-DK-083912]; National
Institute of Diabetes, Digestive, and Kidney Diseases [U54-DK-083912];
University of Michigan; NephCure Kidney International; Halpin
Foundation; NephCure-ASN Foundation; Intramural Research Program of the
NIH, National Cancer Institute, Center for Cancer Research;
[K08-DK088944]
FX The Nephrotic Syndrome Study Network Consortium (U54-DK-083912) is a
part of the National Center for Advancing Translational Sciences, Rare
Disease Clinical Research Network, supported through a collaboration
between the Office of Rare Diseases Research, NCATS, and the National
Institute of Diabetes, Digestive, and Kidney Diseases. Additional
funding and/or programmatic support for this project has also been
provided by the University of Michigan, NephCure Kidney International,
and the Halpin Foundation. Dr. Jeffrey Hodgin is supported by
K08-DK088944 and the NephCure-ASN Foundation. Additional support in part
was provided by the Intramural Research Program of the NIH, National
Cancer Institute, Center for Cancer Research.
NR 22
TC 0
Z9 0
U1 2
U2 2
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUN 16
PY 2016
VL 11
IS 6
AR e0156441
DI 10.1371/journal.pone.0156441
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DO8JO
UT WOS:000378029800005
PM 27310011
ER
PT J
AU Wenger, DS
Kawut, SM
Ding, JZ
Bluemke, DA
Hough, CL
Kronmal, RA
Lima, JA
Leary, PJ
AF Wenger, David S.
Kawut, Steven M.
Ding, Jingzhong
Bluemke, David A.
Hough, Catherine L.
Kronmal, Richard A.
Lima, Joao A.
Leary, Peter J.
TI Pericardial Fat and Right Ventricular Morphology: The Multi-Ethnic Study
of Atherosclerosis-Right Ventricle Study (MESA-RV)
SO PLOS ONE
LA English
DT Article
ID EPICARDIAL ADIPOSE-TISSUE; RIGHT-HEART-FAILURE; METABOLIC SYNDROME;
CARDIOVASCULAR-DISEASE; MOLECULAR-MECHANISMS; RISK-FACTORS; ADULTS;
ASSOCIATION; VOLUME; PLAQUE
AB Background
Pericardial fat has been implicated in the pathogenesis of obesity-related cardiovascular disease. Proposed mechanisms may be relevant in right heart failure, but relationships between pericardial fat and right ventricular (RV) morphology have not been explored.
Methods
The Multi-Ethnic Study of Atherosclerosis is a prospective cohort that enrolled participants without clinical cardiovascular disease. Pericardial fat was measured using computed tomography and RV parameters using cardiac MRI. Linear regression estimated associations of pericardial fat with RV mass, RV end diastolic volume (RV-EDV), RV end systolic volume (RV-ESV), RV stroke volume (RV-SV), and RV ejection fraction (RV-EF). Limited models adjusted for age, gender, race, height, and study site with and without weight. Fully adjusted models also accounted for socioeconomic parameters and health behaviors. Adjustment for left ventricular morphology, metabolic syndrome, and systemic inflammation was also performed.
Results
The study sample included 3988 participants with complete assessment of RV morphology, pericardial fat and all covariates. Greater pericardial fat volume was associated with reduced RV mass (-0.3g per 40 cm(3) increase in pericardial fat, p<0.001), smaller RV-EDV (-3.7ml per 40 cm(3) increase in pericardial fat, p<0.001), smaller RV-ESV (-1.0ml per 40cm(3) increase in pericardial fat, p<0.001), and smaller RV-SV (-2.7mL per 40 cm(3) increase in pericardial fat, p<0.001) in participants after adjustment for weight. Associations were unchanged when accounting for health behaviors, markers of systemic inflammation, and the metabolic syndrome.
Conclusions
Greater pericardial fat was associated with reduced RV mass, smaller RV-EDV, smaller RV-ESV, and smaller RV-SV in participants after adjustment for weight. Relationships between pericardial fat and RV morphology could be relevant to diseases of right heart failure.
C1 [Wenger, David S.] Univ Washington, Dept Gen Internal Med, Seattle, WA 98195 USA.
[Kawut, Steven M.] Univ Penn, Perelman Sch Med, Div Pulm & Crit Care Med, Dept Med & Epidemiol, Philadelphia, PA 19104 USA.
[Ding, Jingzhong] Wake Forest Univ, Dept Gen Internal Med, Winston Salem, NC 27109 USA.
[Bluemke, David A.] NIH, Dept Radiol, Div Radiol & Imaging Sci, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA.
[Hough, Catherine L.; Leary, Peter J.] Univ Washington, Dept Gen Internal Med, Div Pulm & Crit Care, Seattle, WA 98195 USA.
[Kronmal, Richard A.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
[Lima, Joao A.] Johns Hopkins Univ, Dept Radiol, Baltimore, MD USA.
RP Leary, PJ (reprint author), Univ Washington, Dept Gen Internal Med, Div Pulm & Crit Care, Seattle, WA 98195 USA.
EM learyp@uw.edu
OI Bluemke, David/0000-0002-8323-8086; Leary, Peter/0000-0001-5716-248X
FU National Heart, Lung, and Blood Institute [N01-HC-95159, N01-HC-95160,
N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165,
N01-HC-95166, N01-HC-95167, N01-HC-95168, N01-HC-95169]; NCRR
[UL1-TR-000040, UL1-TR-001079]; National Center for Advancing
Translational Sciences [KL2TR000421]
FX This research was supported by contracts N01-HC-95159, N01-HC-95160,
N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165,
N01-HC-95166, N01-HC-95167, N01-HC-95168 and N01-HC-95169 from the
National Heart, Lung, and Blood Institute and by grants UL1-TR-000040
and UL1-TR-001079 from NCRR, and KL2TR000421 from the National Center
for Advancing Translational Sciences.
NR 30
TC 1
Z9 1
U1 0
U2 0
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUN 16
PY 2016
VL 11
IS 6
AR e0157654
DI 10.1371/journal.pone.0157654
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DO8JO
UT WOS:000378029800116
PM 27311062
ER
PT J
AU Dayan, E
Laor-Maayany, R
Censor, N
AF Dayan, Eran
Laor-Maayany, Rony
Censor, Nitzan
TI Reward disrupts reactivated human skill memory
SO SCIENTIFIC REPORTS
LA English
DT Article
ID LONG-TERM-MEMORY; PREDICTION ERROR; MOTOR CORTEX; FEAR MEMORY;
RECONSOLIDATION; BRAIN; RETRIEVAL; CONSOLIDATION; INTERFERENCE; SYSTEMS
AB Accumulating evidence across species and memory domains shows that when an existing memory is reactivated, it becomes susceptible to modifications. However, the potential role of reward signals in these mechanisms underlying human memory dynamics is unknown. Leaning on a wealth of findings on the role of reward in reinforcing memory, we tested the impact of reinforcing a skill memory trace with monetary reward following memory reactivation, on strengthening of the memory trace. Reinforcing reactivated memories did not strengthen the memory, but rather led to disruption of the memory trace, breaking down the link between memory reactivation and subsequent memory strength. Statistical modeling further revealed a strong mediating role for memory reactivation in linking between memory encoding and subsequent memory strength only when the memory was replayed without reinforcement. We suggest that, rather than reinforcing the existing memory trace, reward creates a competing memory trace, impairing expression of the original reward-free memory. This mechanism sheds light on the processes underlying skill acquisition, having wide translational implications.
C1 [Dayan, Eran] NINDS, NIH, Bethesda, MD 20892 USA.
[Laor-Maayany, Rony; Censor, Nitzan] Tel Aviv Univ, Sch Psychol Sci, IL-69978 Tel Aviv, Israel.
[Laor-Maayany, Rony; Censor, Nitzan] Tel Aviv Univ, Sagol Sch Neurosci, IL-69978 Tel Aviv, Israel.
RP Censor, N (reprint author), Tel Aviv Univ, Sch Psychol Sci, IL-69978 Tel Aviv, Israel.; Censor, N (reprint author), Tel Aviv Univ, Sagol Sch Neurosci, IL-69978 Tel Aviv, Israel.
EM censornitzan@post.tau.ac.il
FU intramural program of the National Institute of Neurological Disorders
and Stroke; I-CORE program of the Planning and Budgeting Committee; ISF
[51/11]
FX Eran Dayan was supported by the intramural program of the National
Institute of Neurological Disorders and Stroke. Nitzan Censor was
supported by the I-CORE program of the Planning and Budgeting Committee
and The ISF (grant 51/11).
NR 49
TC 1
Z9 1
U1 2
U2 5
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2045-2322
J9 SCI REP-UK
JI Sci Rep
PD JUN 16
PY 2016
VL 6
AR 28270
DI 10.1038/srep28270
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DO9LO
UT WOS:000378108100001
PM 27306380
ER
PT J
AU Torn, C
Liu, X
Hagopian, W
Lernmark, A
Simell, O
Rewers, M
Ziegler, AG
Schatz, D
Akolkar, B
Onengut-Gumuscu, S
Chen, WM
Toppari, J
Mykkanen, J
Ilonen, J
Rich, SS
She, JX
Sharma, A
Steck, A
Krischer, J
AF Torn, Carina
Liu, Xiang
Hagopian, William
Lernmark, Ake
Simell, Olli
Rewers, Marian
Ziegler, Anette-G
Schatz, Desmond
Akolkar, Beena
Onengut-Gumuscu, Suna
Chen, Wei-Min
Toppari, Jorma
Mykkanen, Juha
Ilonen, Jorma
Rich, Stephen S.
She, Jin-Xiong
Sharma, Ashok
Steck, Andrea
Krischer, Jeffrey
CA TEDDY Study Grp
TI Complement gene variants in relation to autoantibodies to beta cell
specific antigens and type 1 diabetes in the TEDDY Study
SO SCIENTIFIC REPORTS
LA English
DT Article
ID ANTIBODY STANDARDIZATION PROGRAM; SYSTEMIC-LUPUS-ERYTHEMATOSUS;
GLUTAMIC-ACID DECARBOXYLASE; GENOME-WIDE ASSOCIATION; MACULAR
DEGENERATION; EXTENDED HAPLOTYPES; ISLET ANTIGEN-2; CLASS-I; RISK; HLA
AB A total of 15 SNPs within complement genes and present on the ImmunoChip were analyzed in The Environmental Determinants of Diabetes in the Young (TEDDY) study. A total of 5474 subjects were followed from three months of age until islet autoimmunity (IA: n = 413) and the subsequent onset of type 1 diabetes (n = 115) for a median of 73 months (IQR 54-91). Three SNPs within ITGAM were nominally associated (p < 0.05) with IA: rs1143678 [Hazard ratio; HR 0.80; 95% CI 0.66-0.98; p = 0.032], rs1143683 [HR 0.80; 95% CI 0.65-0.98; p = 0.030] and rs4597342 [HR 1.16; 95% CI 1.01-1.32; p = 0.041]. When type 1 diabetes was the outcome, in DR3/4 subjects, there was nominal significance for two SNPs: rs17615 in CD21 [HR 1.52; 95% CI 1.05-2.20; p = 0.025] and rs4844573 in C4BPA [HR 0.63; 95% CI 0.43-0.92; p = 0.017]. Among DR4/4 subjects, rs2230199 in C3 was significantly associated [HR 3.20; 95% CI 1.75-5.85; p = 0.0002, uncorrected] a significance that withstood Bonferroni correction since it was less than 0.000833 (0.05/60) in the HLA-specific analyses. SNPs within the complement genes may contribute to IA, the first step to type 1 diabetes, with at least one SNP in C3 significantly associated with clinically diagnosed type 1 diabetes.
C1 [Torn, Carina; Lernmark, Ake] Lund Univ, Dept Clin Sci, CRC, Malmo, Sweden.
[Liu, Xiang; Krischer, Jeffrey] Univ S Florida, Morsani Coll Med, Hlth Informat Inst, Tampa, FL USA.
[Hagopian, William] Pacific Northwest Diabet Res Inst, Seattle, WA USA.
[Simell, Olli; Toppari, Jorma; Mykkanen, Juha] Turku Univ Hosp, Dept Pediat, FIN-20520 Turku, Finland.
[Rewers, Marian; Steck, Andrea] Univ Colorado, Barbara Davis Ctr Childhood Diabet, Aurora, CO USA.
[Ziegler, Anette-G] Helmholtz Zentrum, Diabet Res Inst, Munich, Germany.
[Ziegler, Anette-G] Tech Univ Munich, Klinikum Rechts Isar, Neuherberg, Germany.
[Ziegler, Anette-G] Forschergrp Diabet eV, Neuherberg, Germany.
[Schatz, Desmond] Univ Florida, Dept Pediat, Gainesville, FL USA.
[Akolkar, Beena] NIDDK, Bethesda, MD 20892 USA.
[Onengut-Gumuscu, Suna; Chen, Wei-Min; Rich, Stephen S.] Univ Virginia, Ctr Publ Hlth Gen, Charlottesville, VA USA.
[Toppari, Jorma; Mykkanen, Juha; Ilonen, Jorma] Univ Turku, Dept Phys, SF-20500 Turku, Finland.
[Toppari, Jorma; Mykkanen, Juha; Ilonen, Jorma] Univ Turku, Dept Pediat, Turku, Finland.
[She, Jin-Xiong; Sharma, Ashok] Augusta Univ, Med Coll Georgia, Ctr Biotechnol & Genom Med, Augusta, GA USA.
RP Torn, C (reprint author), Lund Univ, Dept Clin Sci, CRC, Malmo, Sweden.
EM Carina.Torn@med.lu.se
RI Mykkanen, Juha/Q-1663-2015;
OI Mykkanen, Juha/0000-0001-9898-2660; Chen, Wei-Min/0000-0002-2643-2333
FU National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
[U01 DK63829, U01 DK63861, U01 DK63821, U01 DK63865, U01 DK63863, U01
DK63836, U01 DK63790, UC4 DK63829, UC4 DK63861, UC4 DK63821, UC4
DK63865, UC4 DK63863, UC4 DK63836, UC4 DK95300, UC4 DK100238,
HHSN267200700014C]; National Institute of Allergy and Infectious
Diseases (NIAID); National Institute of Child Health and Human
Development (NICHD); National Institute of Environmental Health Sciences
(NIEHS); Juvenile Diabetes Research Foundation (JDRF); Centers for
Disease Control and Prevention (CDC); NIH/NCATS Clinical and
Translational Science Awards [UL1 TR000064, UL1 TR001082]
FX Funded by U01 DK63829, U01 DK63861, U01 DK63821, U01 DK63865, U01
DK63863, U01 DK63836, U01 DK63790, UC4 DK63829, UC4 DK63861, UC4
DK63821, UC4 DK63865, UC4 DK63863, UC4 DK63836, UC4 DK95300, and UC4
DK100238, and Contract No. HHSN267200700014C from the National Institute
of Diabetes and Digestive and Kidney Diseases (NIDDK), National
Institute of Allergy and Infectious Diseases (NIAID), National Institute
of Child Health and Human Development (NICHD), National Institute of
Environmental Health Sciences (NIEHS), Juvenile Diabetes Research
Foundation (JDRF), and Centers for Disease Control and Prevention (CDC).
This work supported in part by the NIH/NCATS Clinical and Translational
Science Awards to the University of Florida (UL1 TR000064) and the
University of Colorado (UL1 TR001082).
NR 42
TC 1
Z9 1
U1 3
U2 5
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2045-2322
J9 SCI REP-UK
JI Sci Rep
PD JUN 16
PY 2016
VL 6
AR 27887
DI 10.1038/srep27887
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DO8JG
UT WOS:000378028900001
PM 27306948
ER
PT J
AU Merk, A
Bartesaghi, A
Banerjee, S
Falconieri, V
Rao, P
Davis, MI
Pragani, R
Boxer, MB
Earl, LA
Milne, JLS
Subramaniam, S
AF Merk, Alan
Bartesaghi, Alberto
Banerjee, Soojay
Falconieri, Veronica
Rao, Prashant
Davis, Mindy I.
Pragani, Rajan
Boxer, Matthew B.
Earl, Lesley A.
Milne, Jacqueline L. S.
Subramaniam, Sriram
TI Breaking Cryo-EM Resolution Barriers to Facilitate Drug Discovery
SO CELL
LA English
DT Article
ID MUTANT ISOCITRATE DEHYDROGENASE; LARGE RIBOSOMAL-SUBUNIT; CRYOELECTRON
MICROSCOPY; ELECTRON CRYOMICROSCOPY; ANGSTROM RESOLUTION;
LACTATE-DEHYDROGENASE; GLUTAMATE-DEHYDROGENASE; SELECTIVE-INHIBITION;
BETA-GALACTOSIDASE; MECHANISM
AB Recent advances in single-particle cryoelecton microscopy (cryo-EM) are enabling generation of numerous near- atomic resolution structures for well-ordered protein complexes with sizes >= similar to 200 kDa. Whether cryo-EM methods are equally useful for high-resolution structural analysis of smaller, dynamic protein complexes such as those involved in cellular metabolism remains an important question. Here, we present 3.8 angstrom resolution cryo-EM structures of the cancer target isocitrate dehydrogenase (93 kDa) and identify the nature of conformational changes induced by binding of the allosteric small-molecule inhibitor ML309. We also report 2.8-angstrom- and 1.8-angstrom-resolution structures of lactate dehydrogenase (145 kDa) and glutamate dehydrogenase (334 kDa), respectively. With these results, two perceived barriers in single-particle cryo-EM are overcome: (1) crossing 2 angstrom resolution and (2) obtaining structures of proteins with sizes < 100 kDa, demonstrating that cryo-EM can be used to investigate a broad spectrum of drug-target interactions and dynamic conformational states.
C1 [Merk, Alan; Bartesaghi, Alberto; Banerjee, Soojay; Falconieri, Veronica; Rao, Prashant; Earl, Lesley A.; Milne, Jacqueline L. S.; Subramaniam, Sriram] NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Davis, Mindy I.; Pragani, Rajan; Boxer, Matthew B.] Natl Ctr Adv Translat Sci, 9800 Med Ctr Dr, Rockville, MD 20850 USA.
RP Subramaniam, S (reprint author), NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM ss1@nih.gov
FU Center for Cancer Research, National Cancer Institute, NIH in Bethesda
FX This research was supported by funds from the Center for Cancer
Research, National Cancer Institute, NIH in Bethesda. We thank Kieran
Moynihan, Robert Mueller, and Joe Cometa for technical assistance with
electron microscopy; Fred Ulmer, Paul Mooney, and Chris Booth for advice
and assistance with optimizing K2 detector performance; and Rishub Jain,
Jierui Fang, and Amy Jin for assistance with data analysis. This work
utilized the computational resources of the NIH HPC Biowulf cluster
(http://hpc.nih.gov).
NR 49
TC 26
Z9 28
U1 32
U2 50
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0092-8674
EI 1097-4172
J9 CELL
JI Cell
PD JUN 16
PY 2016
VL 165
IS 7
BP 1698
EP 1707
DI 10.1016/j.cell.2016.05.040
PG 10
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA DO8VD
UT WOS:000378062000020
PM 27238019
ER
PT J
AU Zofall, M
Smith, DR
Mizuguchi, T
Dhakshnamoorthy, J
Grewal, SIS
AF Zofall, Martin
Smith, Deborah R.
Mizuguchi, Takeshi
Dhakshnamoorthy, Jothy
Grewal, Shiv I. S.
TI Taz1-Shelterin Promotes Facultative Heterochromatin Assembly at
Chromosome-Internal Sites Containing Late Replication Origins
SO MOLECULAR CELL
LA English
DT Article
ID JMJC DOMAIN PROTEIN; CONTROLS DNA-REPLICATION; COMMON FRAGILE SITE;
FISSION YEAST; SCHIZOSACCHAROMYCES-POMBE; BINDING-PROTEIN; HISTONE
MODIFICATION; TELOMERE LENGTH; COMPLEX; RNAI
AB Facultative heterochromatin regulates gene expression, but its assembly is poorly understood. Previously, we identified facultative heterochromatin islands in the fission yeast genome and found that RNA elimination machinery promotes island assembly at meiotic genes. Here, we report that Taz1, a component of the telomere protection complex Shelterin, is required to assemble heterochromatin islands at regions corresponding to late replication origins that are sites of double-strand break formation during meiosis. The loss of Taz1 or other Shelterin subunits, including Ccq1 that interacts with Clr4/Suv39h, abolishes heterochromatin at late origins and causes derepression of associated genes. Moreover, the late-origin regulator Rif1 affects heterochromatin at Taz1-dependent islands and subtelomeric regions. We explore the connection between facultative heterochromatin and replication control and show that heterochromatin machinery affects replication timing. These analyses reveal the role of Shelterin in facultative heterochromatin assembly at late origins, which has important implications for genome stability and gene regulation.
C1 [Zofall, Martin; Smith, Deborah R.; Mizuguchi, Takeshi; Dhakshnamoorthy, Jothy; Grewal, Shiv I. S.] NCI, Lab Biochem & Mol Biol, NIH, Bethesda, MD 20892 USA.
[Smith, Deborah R.] Columbia Univ Coll Phys & Surg, 630 West 168th St, New York, NY 10032 USA.
RP Grewal, SIS (reprint author), NCI, Lab Biochem & Mol Biol, NIH, Bethesda, MD 20892 USA.
EM grewals@mail.nih.gov
FU Intramural Research Program of the National Institutes of Health,
National Cancer Institute
FX We thank Amikam Cohen, Hisao Masukata, Fuyuki Ishikawa, Gerry Smith, and
Julia Cooper for sharing strains and methods used in this study and
Julia Cooper for providing anti-Taz1 antibody. We also thank Ke Zhang
and Chanan Rubin for their help with some experiments, Jemima Barrowman
for editing the manuscript, and members of the S.I.S.G. lab for helpful
suggestions. This work was supported by the Intramural Research Program
of the National Institutes of Health, National Cancer Institute.
NR 61
TC 5
Z9 5
U1 2
U2 5
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1097-2765
EI 1097-4164
J9 MOL CELL
JI Mol. Cell
PD JUN 16
PY 2016
VL 62
IS 6
BP 862
EP 874
DI 10.1016/j.molcel.2016.04.034
PG 13
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA DP1BI
UT WOS:000378224900008
PM 27264871
ER
PT J
AU Palazzo, E
Kellett, M
Cataisson, C
Gormley, A
Bible, PW
Pietroni, V
Radoja, N
Hwang, J
Blumenberg, M
Yuspa, SH
Morasso, MI
AF Palazzo, E.
Kellett, M.
Cataisson, C.
Gormley, A.
Bible, P. W.
Pietroni, V.
Radoja, N.
Hwang, J.
Blumenberg, M.
Yuspa, S. H.
Morasso, M. I.
TI The homeoprotein DLX3 and tumor suppressor p53 co-regulate cell cycle
progression and squamous tumor growth
SO ONCOGENE
LA English
DT Article
ID ECTODERMAL DYSPLASIAS; HUMAN KERATINOCYTES; HOMEOBOX GENE; EPIDERMAL
DIFFERENTIATION; BINDING-SITES; STEM-CELLS; P63; CANCER; SKIN;
EXPRESSION
AB Epidermal homeostasis depends on the coordinated control of keratinocyte cell cycle. Differentiation and the alteration of this balance can result in neoplastic development. Here we report on a novel DLX3-dependent network that constrains epidermal hyperplasia and squamous tumorigenesis. By integrating genetic and transcriptomic approaches, we demonstrate that DLX3 operates through a p53-regulated network. DLX3 and p53 physically interact on the p21 promoter to enhance p21 expression. Elevating DLX3 in keratinocytes produces a G1-S blockade associated with p53 signature transcriptional profiles. In contrast, DLX3 loss promotes a mitogenic phenotype associated with constitutive activation of ERK. DLX3 expression is lost in human skin cancers and is extinguished during progression of experimentally induced mouse squamous cell carcinoma (SCC). Reinstatement of DLX3 function is sufficient to attenuate the migration of SCC cells, leading to decreased wound closure. Our data establish the DLX3-p53 interplay as a major regulatory axis in epidermal differentiation and suggest that DLX3 is a modulator of skin carcinogenesis.
C1 [Palazzo, E.; Kellett, M.; Gormley, A.; Bible, P. W.; Pietroni, V.; Radoja, N.; Hwang, J.; Morasso, M. I.] NIAMS, Skin Biol Lab, NIH, Bldg 50,Room 1523, Bethesda, MD 20892 USA.
[Cataisson, C.; Yuspa, S. H.] NCI, Lab Canc Biol & Genet, NIH, Bethesda, MD 20892 USA.
[Blumenberg, M.] NYU, Dept Dermatol, New York, NY 10016 USA.
RP Morasso, MI (reprint author), NIAMS, Skin Biol Lab, NIH, Bldg 50,Room 1523, Bethesda, MD 20892 USA.
EM morasso@nih.gov
RI Palazzo, Elisabetta/J-5287-2016;
OI Palazzo, Elisabetta/0000-0002-0812-5524; Blumenberg,
Miroslav/0000-0002-8672-7774
FU Intramural Research Program of the National Institute of Arthritis and
Musculoskeletal and Skin Diseases of the National Institutes of Health
[ZIA AR041124-14]
FX We thank current and past members of the Laboratory of Skin Biology and
members of the Laboratory of Cancer Biology and Genetics, and Dr Mark
Udey for helpful discussions. We also thank Andrew Ryscavage (LCBG),
Gustavo Gutierrez-Cruz (NIAMS Genome Analysis Core Facility), Dr
Hong-Wei Sun (Biodata Mining and Discovery Section, NIAMS) and Kristina
Zaal of the NIAMS Light Imaging Core Facility. This work was supported
by the Intramural Research Program of the National Institute of
Arthritis and Musculoskeletal and Skin Diseases of the National
Institutes of Health (M.I.M. ZIA AR041124-14).
NR 61
TC 2
Z9 2
U1 2
U2 2
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0950-9232
EI 1476-5594
J9 ONCOGENE
JI Oncogene
PD JUN 16
PY 2016
VL 35
IS 24
BP 3114
EP 3124
DI 10.1038/onc.2015.380
PG 11
WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
GA DO9GI
UT WOS:000378092700004
PM 26522723
ER
PT J
AU Jones, DS
Grady, C
Lederer, SE
AF Jones, David S.
Grady, Christine
Lederer, Susan E.
TI "Ethics and Clinical Research" - The 50th Anniversary of Beecher's
Bombshell
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Editorial Material
ID HUMAN-EXPERIMENTATION; INFORMED-CONSENT
C1 [Jones, David S.] Harvard Univ, Sch Med, Dept Global Hlth & Social Med, Boston, MA USA.
[Jones, David S.] Harvard Univ, Dept Hist Sci, Cambridge, MA 02138 USA.
[Grady, Christine] NIH, Dept Bioeth, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA.
[Lederer, Susan E.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Med Hist & Bioeth, Madison, WI 53706 USA.
RP Jones, DS (reprint author), Harvard Univ, Sch Med, Dept Global Hlth & Social Med, Boston, MA USA.; Jones, DS (reprint author), Harvard Univ, Dept Hist Sci, Cambridge, MA 02138 USA.
NR 49
TC 3
Z9 3
U1 1
U2 2
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
EI 1533-4406
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD JUN 16
PY 2016
VL 374
IS 24
BP 2393
EP 2398
DI 10.1056/NEJMms1603756
PG 6
WC Medicine, General & Internal
SC General & Internal Medicine
GA DO5WW
UT WOS:000377854600016
PM 27305197
ER
PT J
AU Biswas, P
Chavali, VRM
Agnello, G
Stone, E
Chakarova, C
Duncan, JL
Kannabiran, C
Homsher, M
Bhattacharya, SS
Naeem, MA
Kimchi, A
Sharon, D
Iwata, T
Riazuddin, S
Reddy, GB
Hejtmancik, JF
Georgiou, G
Riazuddin, SA
Ayyagari, R
AF Biswas, Pooja
Chavali, Venkata Ramana Murthy
Agnello, Giulia
Stone, Everett
Chakarova, Christina
Duncan, Jacque L.
Kannabiran, Chitra
Homsher, Melissa
Bhattacharya, Shomi S.
Naeem, Muhammad Asif
Kimchi, Adva
Sharon, Dror
Iwata, Takeshi
Riazuddin, Shaikh
Reddy, G. Bhanuprakash
Hejtmancik, J. Fielding
Georgiou, George
Riazuddin, S. Amer
Ayyagari, Radha
TI A missense mutation in ASRGL1 is involved in causing autosomal recessive
retinal degeneration
SO HUMAN MOLECULAR GENETICS
LA English
DT Article
ID STATIONARY NIGHT BLINDNESS; L-ISOASPARTYL METHYLTRANSFERASE; VITELLIFORM
MACULAR DYSTROPHY; LEBER CONGENITAL AMAUROSIS; RETINITIS-PIGMENTOSA;
PROTEIN DAMAGE; GENE; IDENTIFICATION; REPAIR; SUBSTRATE
AB Inherited retinal dystrophies are a group of genetically heterogeneous conditions with broad phenotypic heterogeneity. We analyzed a large five-generation pedigree with early-onset recessive retinal degeneration to identify the causative mutation. Linkage analysis and homozygosity mapping combined with exome sequencing were carried out to map the disease locus and identify the p.G178R mutation in the asparaginase like-1 gene (ASRGL1), segregating with the retinal dystrophy phenotype in the study pedigree. ASRGL1 encodes an enzyme that catalyzes the hydrolysis of L-asparagine and isoaspartyl-peptides. Studies on the ASRGL1 expressed in Escherichia coli and transiently transfected mammalian cells indicated that the p.G178R mutation impairs the autocatalytic processing of this enzyme resulting in the loss of functional ASRGL1 and leaving the inactive precursor protein as a destabilized and aggregation-prone protein. A zebrafish model overexpressing the mutant hASRGL1 developed retinal abnormalities and loss of cone photoreceptors. Our studies suggest that the p.G178R mutation in ASRGL1 leads to photoreceptor degeneration resulting in progressive vision loss.
C1 [Biswas, Pooja; Chavali, Venkata Ramana Murthy; Ayyagari, Radha] Univ Calif San Diego, Shiley Eye Inst, 9415 Campus Point Dr,JRC 206, La Jolla, CA 92093 USA.
[Chavali, Venkata Ramana Murthy; Homsher, Melissa] Univ Penn, Ophthalmol, Philadelphia, PA 19104 USA.
[Agnello, Giulia; Stone, Everett; Georgiou, George] Univ Texas Austin, Sect Mol Genet & Microbiol, Dept Biomed Engn, Mol Biosci, Austin, TX 78712 USA.
[Agnello, Giulia; Stone, Everett; Georgiou, George] Univ Texas Austin, Sect Mol Genet & Microbiol, Dept Chem Engn, Mol Biosci, Austin, TX 78712 USA.
[Agnello, Giulia; Stone, Everett; Georgiou, George] Univ Texas Austin, Inst Cell & Mol Biol, Austin, TX 78712 USA.
[Chakarova, Christina; Bhattacharya, Shomi S.] UCL Inst Ophthalmol, 11-43 Bath St, London, England.
[Duncan, Jacque L.] Univ Calif San Francisco, Ophthalmol, San Francisco, CA 94143 USA.
[Kannabiran, Chitra] LVPEI, Kallam Anji Reddy Mol Genet Lab, Kallam Anji Reddy Campus,LV Prasad Marg, Hyderabad 500034, Andhra Pradesh, India.
[Naeem, Muhammad Asif] Univ Punjab, Natl Ctr Excellence Mol Biol, Lahore, Pakistan.
[Kimchi, Adva; Sharon, Dror] Hadassah Hebrew Univ, Med Ctr, Dept Ophthalmol, Jerusalem, Israel.
[Iwata, Takeshi] Natl Hosp Org, Tokyo Med Ctr, Natl Inst Sensory Organs, Div Mol & Cellular Biol, Tokyo, Japan.
[Riazuddin, Shaikh] Univ Hlth Sci Lahore, Allama Iqbal Med Coll, Lahore, Pakistan.
[Riazuddin, Shaikh] Shaheed Zulfiqar Ali Bhutto Med Univ, Natl Ctr Genet Dis, Islamabad, Pakistan.
[Reddy, G. Bhanuprakash] Natl Inst Nutr, Hyderabad 500007, Andhra Pradesh, India.
[Hejtmancik, J. Fielding] NEI, OMGS OGVFB Branch, NIH, Bethesda, MD 20892 USA.
[Riazuddin, S. Amer] Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Baltimore, MD 21205 USA.
RP Ayyagari, R (reprint author), Univ Calif San Diego, Shiley Eye Inst, 9415 Campus Point Dr,JRC 206, La Jolla, CA 92093 USA.; Riazuddin, SA (reprint author), Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Baltimore, MD 21205 USA.
EM riazuddin@jhmi.edu; rayyagari@ucsd.edu
FU Foundation Fighting Blindness; Research to Prevent Blindness; Bright
Focus Foundation [NIH-EY21237, P30-EY22589 CPRIT RP120314]
FX This work was supported by; The Foundation Fighting Blindness, Research
to Prevent Blindness, Bright Focus Foundation grant, NIH-EY21237,
P30-EY22589 CPRIT RP120314.
NR 48
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0964-6906
EI 1460-2083
J9 HUM MOL GENET
JI Hum. Mol. Genet.
PD JUN 15
PY 2016
VL 25
IS 12
BP 2483
EP 2497
DI 10.1093/hmg/ddw113
PG 15
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA EJ2TA
UT WOS:000393062900009
PM 27106100
ER
PT J
AU Chen, MM
O'Mara, TA
Thompson, DJ
Painter, JN
Attia, J
Black, A
Brinton, L
Chanock, S
Chen, C
Cheng, THT
Cook, LS
Crous-Bou, M
Doherty, J
Friedenreich, CM
Garcia-Closas, M
Gaudet, MM
Gorman, M
Haiman, C
Hankinson, SE
Hartge, P
Henderson, BE
Hodgson, S
Holliday, EG
Horn-Ross, PL
Hunter, DJ
Le Marchand, L
Liang, XL
Lissowska, J
Long, JR
Lu, LG
Magliocco, AM
Martin, L
McEvoy, M
Olson, SH
Orlow, I
Pooler, L
Prescott, J
Rastogi, R
Rebbeck, TR
Risch, H
Sacerdote, C
Schumacher, F
Setiawan, VW
Scott, RJ
Sheng, X
Shu, XO
Turman, C
Van Den Berg, D
Wang, ZM
Weiss, NS
Wentzensen, N
Xia, L
Xiang, YB
Yang, HP
Yu, H
Zheng, W
Pharoah, PDP
Dunning, AM
Tomlinson, I
Easton, DF
Kraft, P
Spurdle, AB
De Vivo, I
AF Chen, Maxine M.
O'Mara, Tracy A.
Thompson, Deborah J.
Painter, Jodie N.
Attia, John
Black, Amanda
Brinton, Louise
Chanock, Stephen
Chen, Chu
Cheng, Timothy H. T.
Cook, Linda S.
Crous-Bou, Marta
Doherty, Jennifer
Friedenreich, Christine M.
Garcia-Closas, Montserrat
Gaudet, Mia M.
Gorman, Maggie
Haiman, Christopher
Hankinson, Susan E.
Hartge, Patricia
Henderson, Brian E.
Hodgson, Shirley
Holliday, Elizabeth G.
Horn-Ross, Pamela L.
Hunter, David J.
Le Marchand, Loic
Liang, Xiaolin
Lissowska, Jolanta
Long, Jirong
Lu, Lingeng
Magliocco, Anthony M.
Martin, Lynn
McEvoy, Mark
Olson, Sara H.
Orlow, Irene
Pooler, Loreall
Prescott, Jennifer
Rastogi, Radhai
Rebbeck, Timothy R.
Risch, Harvey
Sacerdote, Carlotta
Schumacher, Frederick
Setiawan, Veronica Wendy
Scott, Rodney J.
Sheng, Xin
Shu, Xiao-Ou
Turman, Constance
Van Den Berg, David
Wang, Zhaoming
Weiss, Noel S.
Wentzensen, Nicholas
Xia, Lucy
Xiang, Yong-Bing
Yang, Hannah P.
Yu, Herbert
Zheng, Wei
Pharoah, Paul D. P.
Dunning, Alison M.
Tomlinson, Ian
Easton, Douglas F.
Kraft, Peter
Spurdle, Amanda B.
De Vivo, Immaculata
CA ANECS
Natl Study Endometrial Canc
TI GWAS meta-analysis of 16 852 women identifies new susceptibility locus
for endometrial cancer
SO HUMAN MOLECULAR GENETICS
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; EPITHELIAL-MESENCHYMAL TRANSITION;
PROSTATE-CANCER; POOR-PROGNOSIS; COLORECTAL-CANCER; COMMON VARIANTS;
FAMILY-HISTORY; LUNG-CANCER; RISK LOCI; SOX4
AB Endometrial cancer is the most common gynecological malignancy in the developed world. Although there is evidence of genetic predisposition to the disease, most of the genetic risk remains unexplained. We present the meta-analysis results of four genome-wide association studies (4907 cases and 11 945 controls total) in women of European ancestry. We describe one new locus reaching genome-wide significance (P<5 x 10(-8)) at 6p22.3 (rs1740828; P = 2.29 x 10(-8), OR = 1.20), providing evidence of an additional region of interest for genetic susceptibility to endometrial cancer.
C1 [Chen, Maxine M.; Crous-Bou, Marta; Hunter, David J.; Turman, Constance; Kraft, Peter; De Vivo, Immaculata] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Program Genet Epidemiol & Stat Genet, Boston, MA 02115 USA.
[O'Mara, Tracy A.; Painter, Jodie N.; Spurdle, Amanda B.; ANECS] QIMR Berghofer Med Res Inst, Dept Genet & Computat Biol, Herston, Qld 4006, Australia.
[Thompson, Deborah J.; Tomlinson, Ian; Easton, Douglas F.] Univ Cambridge, Ctr Canc Genet Epidemiol, Dept Publ Hlth & Primary Care, Cambridge CB1 8RN, England.
[Attia, John; Holliday, Elizabeth G.; Scott, Rodney J.] John Hunter Hosp, Hunter Med Res Inst, Newcastle, NSW 2305, Australia.
[Attia, John; McEvoy, Mark] Univ Newcastle, Sch Med & Publ Hlth, Ctr Clin Epidemiol & Biostat, Newcastle, NSW 2308, Australia.
[Black, Amanda; Brinton, Louise; Chanock, Stephen; Garcia-Closas, Montserrat; Hartge, Patricia; Wang, Zhaoming; Wentzensen, Nicholas; Yang, Hannah P.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Chen, Chu] Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA.
[Cheng, Timothy H. T.; Gorman, Maggie; Martin, Lynn; Natl Study Endometrial Canc] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England.
[Cook, Linda S.] Univ New Mexico, Albuquerque, NM 87131 USA.
[Cook, Linda S.] Alberta Hlth Serv, Dept Populat Hlth Res, Div Canc Care, Calgary, AB, Canada.
[Crous-Bou, Marta; Hankinson, Susan E.; Prescott, Jennifer; De Vivo, Immaculata] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA.
[Crous-Bou, Marta; Hankinson, Susan E.; Prescott, Jennifer; De Vivo, Immaculata] Harvard Med Sch, Boston, MA 02115 USA.
[Doherty, Jennifer] Dartmouth Coll, Sch Med, Lebanon, NH 03755 USA.
[Friedenreich, Christine M.] Alberta Hlth Serv, Canc Control Alberta, Dept Canc Epidemiol & Prevent Res, Calgary, AB, Canada.
[Garcia-Closas, Montserrat] Inst Canc Res, Div Genet & Epidemiol, London, England.
[Gaudet, Mia M.] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA.
[Haiman, Christopher; Henderson, Brian E.; Pooler, Loreall; Schumacher, Frederick; Setiawan, Veronica Wendy; Sheng, Xin; Van Den Berg, David; Xia, Lucy] Univ Southern Calif, Los Angeles, CA 90033 USA.
[Hankinson, Susan E.] Univ Massachusetts, Dept Biostat & Epidemiol, Amherst, MA 01003 USA.
[Hodgson, Shirley] St Georges Univ London, Dept Clin Genet, London SW17 0RE, England.
[Horn-Ross, Pamela L.] Canc Prevent Inst Calif, Fremont, CA 94538 USA.
[Le Marchand, Loic; Yu, Herbert] Univ Hawaii, Ctr Canc, Honolulu, HI 96813 USA.
[Liang, Xiaolin; Olson, Sara H.; Orlow, Irene; Rastogi, Radhai] Mem Sloan Kettering Canc Ctr, New York, NY 10065 USA.
[Lissowska, Jolanta] M Sklodowska Curie Canc Ctr, Dept Canc Epidemiol & Prevent, Warsaw, Poland.
[Lissowska, Jolanta] Inst Oncol, Warsaw, Poland.
[Long, Jirong; Shu, Xiao-Ou; Zheng, Wei] Vanderbilt Univ, Med Ctr, Vanderbilt Ingram Canc Ctr, Dept Med,Vanderbilt Epidemiol Ctr, Nashville, TN 27232 USA.
[Lu, Lingeng; Risch, Harvey] Yale Univ, Sch Publ Hlth, New Haven, CT 06510 USA.
[Magliocco, Anthony M.] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA.
[Rebbeck, Timothy R.] Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA.
[Sacerdote, Carlotta] Ctr Canc Prevent CPO Piemonte, Turin, Italy.
[Sacerdote, Carlotta] Human Genet Fdn HuGeF, Turin, Italy.
[Scott, Rodney J.] John Hunter Hosp, Hunter Area Pathol Serv, Newcastle, NSW 2305, Australia.
[Scott, Rodney J.] Univ Newcastle, Sch Biomed Sci & Pharm, Newcastle, NSW 2308, Australia.
[Weiss, Noel S.] Univ Washington, Seattle, WA 19024 USA.
[Xiang, Yong-Bing] Shanghai Canc Inst, Dept Epidemiol, Shanghai, Peoples R China.
[Pharoah, Paul D. P.; Dunning, Alison M.; Easton, Douglas F.] Univ Cambridge, Ctr Canc Genet Epidemiol, Dept Oncol, Cambridge CB1 8RN, England.
RP De Vivo, I (reprint author), Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Program Genet Epidemiol & Stat Genet, Boston, MA 02115 USA.; De Vivo, I (reprint author), Brigham & Womens Hosp, Dept Med, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA.; De Vivo, I (reprint author), Harvard Med Sch, Boston, MA 02115 USA.
EM nhidv@channing.harvard.edu
FU National Health and Medical Research Council of Australia [339435];
Cancer Council Queensland [4196615]; Cancer Council Tasmania [403031,
457636]; Cancer Research UK [C490/A10124]; National Health and Medical
Research Council [552402]; Medical Research Council [G0000934]; Wellcome
Trust [068545/Z/02, 085475]; EU FP7 CHIBCHA grant; CORGI by Cancer
Research UK; National Health and Medical Research Council of Australia
(NHMRC); NHMRC [APP1031333]; National Health and Medical Research
Council (NHMRC); Joseph Mitchell Trust; Cancer Research UK; Oxford
Comprehensive Biomedical Research Centre; NCI [5T32CA009001-38]; NCI,
NIH [UM1 CA186107, P01 CA087969, R01 CA49449, 1R01 CA134958, 2R01
CA082838, CA54281, CA128008, R01 CA91019, R01 CA77398]; NIH [RO1
CA105212, RO1 CA 87538, RO1 CA75977, RO3 CA80636, NO1 HD23166, R35
CA39779, KO5 CA92002]; Fred Hutchinson Cancer Research Center;
California Breast Cancer Research Fund [97-10500]; Intramural Research
Program of the NCI; Extramural and the Intramural Research Programs of
the NCI
FX ANECS recruitment was supported by project grants from the National
Health and Medical Research Council of Australia (ID 339435), The Cancer
Council Queensland (ID 4196615) and Cancer Council Tasmania (ID 403031
and ID 457636). SEARCH recruitment was funded by a programme grant from
Cancer Research UK [C490/A10124]. Case genotyping was supported by the
National Health and Medical Research Council (ID 552402). Control data
were generated by the Wellcome Trust Case Control Consortium (WTCCC),
and a full list of the investigators who contributed to the generation
of the data is available from the WTCCC website. We acknowledge use of
DNA from the British 1958 Birth Cohort collection, funded by the Medical
Research Council grant G0000934 and the Wellcome Trust grant
068545/Z/02-funding for this project was provided by the Wellcome Trust
under award 085475. NSECG was supported by the EU FP7 CHIBCHA grant and
CORGI by Cancer Research UK. Recruitment of the QIMR controls was
supported by the National Health and Medical Research Council of
Australia (NHMRC). The University of Newcastle, the Gladys M Brawn
Senior Research Fellowship scheme, The Vincent Fairfax Family
Foundation, the Hunter Medical Research Institute and the Hunter Area
Pathology Service all contributed towards the costs of establishing the
Hunter Community Study. T.O'M and J.N.P. are supported by NHMRC project
grant (ID APP1031333). A.B.S. is supported by the National Health and
Medical Research Council (NHMRC) Fellowship Scheme. D.F.E. is a
Principal Research Fellow of Cancer Research UK. A.M.D. was supported by
the Joseph Mitchell Trust. I.T. is supported by Cancer Research UK and
the Oxford Comprehensive Biomedical Research Centre. M.M.C. is supported
by training grant 5T32CA009001-38 from the NCI. The Nurses' Health Study
(NHS) is supported by the NCI, NIH Grants Number UM1 CA186107, P01
CA087969, R01 CA49449, 1R01 CA134958 and 2R01 CA082838. The Connecticut
Endometrial Cancer Study was supported by NCI, NIH Grant Number 2R01
CA082838. The Fred Hutchinson Cancer Research Center (FHCRC) is
supported by NCI, NIH Grant Number 2R01 CA082838, NIH RO1 CA105212, RO1
CA 87538, RO1 CA75977, RO3 CA80636, NO1 HD23166, R35 CA39779, KO5
CA92002 and funds from the Fred Hutchinson Cancer Research Center. The
Multiethnic Cohort Study (MEC) is supported by the NCI, NHI Grants
Number CA54281, CA128008 and 2R01 CA082838. The California Teachers
Study (CTS) is supported by NCI, NIH Grant Number 2R01 CA082838, R01
CA91019 and R01 CA77398, and contract 97-10500 from the California
Breast Cancer Research Fund. The Polish Endometrial Cancer Study (PECS)
is supported by the Intramural Research Program of the NCI. The
Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO) is
supported by the Extramural and the Intramural Research Programs of the
NCI.
NR 64
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0964-6906
EI 1460-2083
J9 HUM MOL GENET
JI Hum. Mol. Genet.
PD JUN 15
PY 2016
VL 25
IS 12
BP 2612
EP 2620
DI 10.1093/hmg/ddw092
PG 9
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA EJ2TA
UT WOS:000393062900019
PM 27008869
ER
PT J
AU Jin, JF
Krishnamachary, B
Mironchik, Y
Kobayashi, H
Bhujwalla, ZM
AF Jin, Jiefu
Krishnamachary, Balaji
Mironchik, Yelena
Kobayashi, Hisataka
Bhujwalla, Zaver M.
TI Phototheranostics of CD44-positive cell populations in triple negative
breast cancer
SO SCIENTIFIC REPORTS
LA English
DT Article
ID NEAR-INFRARED PHOTOIMMUNOTHERAPY; GROWTH-FACTOR RECEPTOR; PHASE-I
THERAPY; STEM-CELLS; BIVATUZUMAB MERTANSINE; TUMOR-MODEL; CARCINOMA;
HEAD; NECK; THERAPEUTICS
AB Triple-negative breast cancer (TNBC) is one of the most lethal subtypes of breast cancer that has limited treatment options. Its high rates of recurrence and metastasis have been associated, in part, with a subpopulation of breast cancer stem-like cells that are resistant to conventional therapies. A compendium of markers such as CD44(high)/CD24(low), and increased expression of the ABCG2 transporter and increased aldehyde dehydrogenase (ALDH1), have been associated with these cells. We developed a CD44-targeted monoclonal antibody photosensitizer conjugate for combined fluorescent detection and photoimmunotherapy (PIT) of CD44 expressing cells in TNBC. The CD44-targeted conjugate demonstrated acute cell killing of breast cancer cells with high CD44 expression. This cell death process was dependent upon CD44-specific cell membrane binding combined with near-infrared irradiation. The conjugate selectively accumulated in CD44-positive tumors and caused dramatic tumor shrinkage and efficient elimination of CD44-positive cell populations following irradiation. This novel phototheranostic strategy provides a promising opportunity for the destruction of CD44-positive populations that include cancer stem-like cells, in locally advanced primary and metastatic TNBC.
C1 [Jin, Jiefu; Krishnamachary, Balaji; Mironchik, Yelena; Bhujwalla, Zaver M.] Johns Hopkins Univ, Russell H Morgan Dept Radiol & Radiol Sci, Div Canc Imaging Res, Sch Med, Baltimore, MD 21218 USA.
[Kobayashi, Hisataka] NCI, Mol Imaging Program, Ctr Canc Res, US Natl Inst Hlth, Bethesda, MD 20892 USA.
[Bhujwalla, Zaver M.] Johns Hopkins Univ, Sch Med, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21218 USA.
RP Bhujwalla, ZM (reprint author), Johns Hopkins Univ, Russell H Morgan Dept Radiol & Radiol Sci, Div Canc Imaging Res, Sch Med, Baltimore, MD 21218 USA.; Bhujwalla, ZM (reprint author), Johns Hopkins Univ, Sch Med, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21218 USA.
EM zaver@mri.jhu.edu
OI Jin, Jiefu/0000-0002-5318-1111
FU NIH [R01CA136576, R01CA138515, R01CA73850, R01CA82337, P50CA103175];
Commonwealth Foundation
FX This work was supported by NIH R01CA136576, R01CA138515, R01CA73850,
R01CA82337, and P50CA103175, and the Commonwealth Foundation. We thank
Mr. G. Cromwell for maintaining the cell lines and inoculating tumors.
We thank Dr. Marie-France Penet for assistance with the in vivo studies.
We thank Drs. J.S. Lewin and K.M. Horton for their support.
NR 49
TC 1
Z9 1
U1 6
U2 7
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2045-2322
J9 SCI REP-UK
JI Sci Rep
PD JUN 15
PY 2016
VL 6
AR 27871
DI 10.1038/srep27871
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DX8DI
UT WOS:000384617900001
PM 27302409
ER
PT J
AU Shockley, KR
AF Shockley, Keith R.
TI Estimating Potency in High-Throughput Screening Experiments by
Maximizing the Rate of Change in Weighted Shannon Entropy
SO SCIENTIFIC REPORTS
LA English
DT Article
ID ESTROGEN-RECEPTOR-ALPHA; STATISTICAL-ANALYSIS; CHEMICALS; TOXICITY;
AGONISTS; IMPACT; CANCER; ASSAYS
AB High-throughput in vitro screening experiments can be used to generate concentration-response data for large chemical libraries. It is often desirable to estimate the concentration needed to achieve a particular effect, or potency, for each chemical tested in an assay. Potency estimates can be used to directly compare chemical profiles and prioritize compounds for confirmation studies, or employed as input data for prediction modeling and association mapping. The concentration for half-maximal activity derived from the Hill equation model (i.e., AC(50)) is the most common potency measure applied in pharmacological research and toxicity testing. However, the AC(50) parameter is subject to large uncertainty for many concentration-response relationships. In this study we introduce a new measure of potency based on a weighted Shannon entropy measure termed the weighted entropy score (WES). Our potency estimator (Point of Departure, PODWES) is defined as the concentration producing the maximum rate of change in weighted entropy along a concentration-response profile. This approach provides a new tool for potency estimation that does not depend on the assumption of monotonicity or any other pre-specified concentration-response relationship. PODWES estimates potency with greater precision and less bias compared to the conventional AC(50) assessed across a range of simulated conditions.
C1 [Shockley, Keith R.] NIEHS, Biostat & Computat Biol Branch, NIH, 111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA.
RP Shockley, KR (reprint author), NIEHS, Biostat & Computat Biol Branch, NIH, 111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA.
EM shockleykr@niehs.nih.gov
FU Intramural Research Program of the NIH, National Institute of
Environmental Health Sciences [ZIA ES102865]
FX I thank Dr. Raymond Tice (Biomolecular Screening Branch, NIEHS) and Dr.
Grace Kissling (Biostatistics and Computational Biology Branch, NIEHS)
for reviewing the manuscript and providing helpful suggestions. This
work was supported [in part] by the Intramural Research Program of the
NIH, National Institute of Environmental Health Sciences (ZIA ES102865).
NR 34
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2045-2322
J9 SCI REP-UK
JI Sci Rep
PD JUN 15
PY 2016
VL 6
AR 27897
DI 10.1038/srep27897
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DX7IH
UT WOS:000384559800001
PM 27302286
ER
PT J
AU Gomez-Quiroz, LE
Seo, D
Lee, YH
Kitade, M
Gaiser, T
Gillen, M
Lee, SB
Gutierrez-Ruiz, MC
Conner, EA
Factor, VM
Thorgeirsson, SS
Marquardt, JU
AF Gomez-Quiroz, Luis E.
Seo, Daekwan
Lee, Yun-Han
Kitade, Mitsuteru
Gaiser, Timo
Gillen, Matthew
Lee, Seung-Bum
Concepcion Gutierrez-Ruiz, Ma
Conner, Elizabeth A.
Factor, Valentina M.
Thorgeirsson, Snorri S.
Marquardt, Jens U.
TI Loss of c-Met signaling sensitizes hepatocytes to lipotoxicity and
induces cholestatic liver damage by aggravating oxidative stress
SO TOXICOLOGY
LA English
DT Article
DE c-Met; Oxidative stress; Cholestasis; Cholesterol
ID INDUCED FATTY LIVER; GROWTH-FACTOR; ACID-METABOLISM; BILE; PATHWAY;
RECEPTOR; REGENERATION; FAS; TRANSPORTERS; PROTECTION
AB Recent studies confirmed a critical importance of c-Met signaling for liver regeneration by modulating redox balance. Here we used liver-specific conditional knockout mice (MetKO) and a nutritional model of hepatic steatosis to address the role of c-Met in cholesterol-mediated liver toxicity.
Liver injury was assessed by histopathology and plasma enzymes levels. Global transcriptomic changes were examined by gene expression microarray, and key molecules involved in liver damage and lipid homeostasis were evaluated by Western blotting.
Loss of c-Met signaling amplified the extent of liver injury in MetKO mice fed with high-cholesterol diet for 30 days as evidenced by upregulation of liver enzymes and increased synthesis of total bile acids, aggravated inflammatory response and enhanced intrahepatic lipid deposition. Global transcriptomic changes confirmed the enrichment of networks involved in steatosis and cholestasis. In addition, signaling pathways related to glutathione and lipid metabolism, oxidative stress and mitochondria dysfunction were significantly affected by the loss of c-Met function. Mechanistically, exacerbation of oxidative stress in MetKO livers was corroborated by increased lipid and protein oxidation. Western blot analysis further revealed suppression of Erk, NF-kappa B and Nrf2 survival pathways and downstream target genes (e.g. cyclin D1, SOD1, gamma-GCS), as well as up-regulation of proapoptotic signaling (e.g. p53, caspase 3). Consistent with the observed steatotic and cholestatic phenotype, nuclear receptors RAR, RXR showed increased activation while expression levels of CAR, FXR and PPAR-alpha were decreased in MetKO. Collectively, our data provide evidence for the critical involvement of c-Met signaling in cholesterol and bile acids toxicity. (C) 2016 Published by Elsevier Ireland Ltd.
C1 [Gomez-Quiroz, Luis E.; Seo, Daekwan; Lee, Yun-Han; Kitade, Mitsuteru; Gillen, Matthew; Lee, Seung-Bum; Conner, Elizabeth A.; Factor, Valentina M.; Thorgeirsson, Snorri S.] NCI, Expt Carcinogenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Gomez-Quiroz, Luis E.; Concepcion Gutierrez-Ruiz, Ma] Univ Autonoma Metropolitana Iztapalapa, Dept Ciencias Salud, Mexico City, DF, Mexico.
[Lee, Yun-Han] Yonsei Univ, Coll Med, Dept Radiat Oncol, Seoul, South Korea.
[Gaiser, Timo] Univ Med Ctr Mannheim, Inst Pathol, Mannheim, Germany.
[Marquardt, Jens U.] Johannes Gutenberg Univ Mainz, Univ Med Ctr, Dept Med 1, Langenbeckstr 1, D-55131 Mainz, Germany.
RP Marquardt, JU (reprint author), Johannes Gutenberg Univ Mainz, Univ Med Ctr, Dept Med 1, Langenbeckstr 1, D-55131 Mainz, Germany.
EM marquarj@uni-mainz.de
FU National Science Council of Mexico (CONACYT) [252942, 166042, 144805];
German Cancer Aid [DKH 110989]; Volkswagen Foundation (Lichtenberg
program)
FX This work was supported by National Science Council of Mexico (CONACYT)
#252942, 166042 and 144805 for sabbatical support to L.E.G-Q. PRODEP
913026-1461211. The Intramural Research Program of the NIH, National
Cancer Institute, Center for Cancer Research, and J.U.M. is supported by
grants from the German Cancer Aid (DKH 110989) and the Volkswagen
Foundation (Lichtenberg program). We thank Tanya Hoang and Anita Ton for
technical assistance.
NR 41
TC 0
Z9 0
U1 1
U2 1
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0300-483X
J9 TOXICOLOGY
JI Toxicology
PD JUN 15
PY 2016
VL 361
BP 39
EP 48
DI 10.1016/j.tox.2016.07.004
PG 10
WC Pharmacology & Pharmacy; Toxicology
SC Pharmacology & Pharmacy; Toxicology
GA DT5SI
UT WOS:000381542500004
PM 27394961
ER
PT J
AU Wallace, ME
Grantz, KL
Liu, DP
Zhu, YY
Kim, SS
Mendola, P
AF Wallace, Maeve E.
Grantz, Katherine L.
Liu, Danping
Zhu, Yeyi
Kim, Sung Soo
Mendola, Pauline
TI Exposure to Ambient Air Pollution and Premature Rupture of Membranes
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Article
DE ambient air pollution; premature rupture of membranes; preterm birth
ID FINE PARTICULATE MATTER; TIME-SERIES-ANALYSIS; PRETERM BIRTH; OUTCOMES;
RISK; OZONE; WOMEN; COMPLICATIONS; PENNSYLVANIA; INFLAMMATION
AB Premature rupture of membranes (PROM) is a major factor that predisposes women to preterm delivery. Results from previous studies have suggested that there are associations between exposure to air pollution and preterm birth, but evidence of a relationship with PROM is sparse. Modified Community Multiscale Air Quality models were used to estimate mean exposures to particulate matter less than 10 A mu m or less than 2.5 A mu m in aerodynamic diameter, nitrogen oxides, carbon monoxide, sulfur dioxide, and ozone among 223,375 singleton deliveries in the Air Quality and Reproductive Health Study (2002-2008). We used log-linear models with generalized estimating equations to estimate adjusted relative risks and 95% confidence intervals for PROM per each interquartile-range increase in pollutants across the whole pregnancy, on the day of delivery, and 5 hours before delivery. Whole-pregnancy exposures to carbon monoxide and sulfur dioxide were associated with an increased risk of PROM (for carbon monoxide, relative risk (RR) = 1.09, 95% confidence interval (CI): 1.04, 1.14; for sulfur dioxide, RR = 1.15, 95% CI: 1.06, 1.25) but not preterm PROM. Ozone exposure increased the risk of PROM on the day of delivery (RR = 1.06, 95% CI: 1.02, 1.09) and 1 day prior (RR = 1.04, 95% CI: 1.01, 1.07). In the 5 hours preceding delivery, there were 3%-7% increases in risk associated with exposure to ozone and particulate matter less than 2.5 A mu m in aerodynamic diameter and inverse associations with exposure to carbon monoxide and nitrogen oxides. Acute and long-term air pollutant exposures merit further study in relation to PROM.
C1 [Wallace, Maeve E.; Grantz, Katherine L.; Zhu, Yeyi; Kim, Sung Soo; Mendola, Pauline] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Intramural Populat Hlth Res, Rockville, MD USA.
[Liu, Danping] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Biostat & Bioinformat Branch, Div Intramural Populat Hlth Res, Rockville, MD USA.
RP Mendola, P (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Populat Hlth Res, 6100 Execut Blvd, Rockville, MD 20852 USA.
EM Pauline.mendola@nih.gov
OI Mendola, Pauline/0000-0001-5330-2844; Grantz,
Katherine/0000-0003-0276-8534
FU National Institutes of Health, Eunice Kennedy Shriver National Institute
of Child Health and Human Development [HHSN267200603425C]; Air Quality
and Reproductive Health Study [HHSN275200800002I, HHSN27500008]
FX This research was supported by the Intramural Research Program of the
National Institutes of Health, Eunice Kennedy Shriver National Institute
of Child Health and Human Development, including funding for the
Consortium on Safe Labor (contract HHSN267200603425C) and the Air
Quality and Reproductive Health Study (contract HHSN275200800002I, task
order HHSN27500008).
NR 34
TC 0
Z9 0
U1 4
U2 7
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0002-9262
EI 1476-6256
J9 AM J EPIDEMIOL
JI Am. J. Epidemiol.
PD JUN 15
PY 2016
VL 183
IS 12
BP 1114
EP 1121
DI 10.1093/aje/kwv284
PG 8
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA DR2IQ
UT WOS:000379728600007
PM 27188941
ER
PT J
AU Arendt, LH
Ramlau-Hansen, CH
Wilcox, AJ
Henriksen, TB
Olsen, J
Lindhard, MS
AF Arendt, Linn Hakonsen
Ramlau-Hansen, Cecilia Host
Wilcox, Allen J.
Henriksen, Tine Brink
Olsen, Jorn
Lindhard, Morten Sondergaard
TI Placental Weight and Male Genital Anomalies: A Nationwide Danish Cohort
Study
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Article
DE congenital abnormalities; cryptorchidism; hypospadias; placenta;
pregnancy; risk factors
ID GESTATIONAL-AGE; BIRTH-WEIGHT; FETAL-GROWTH; RISK-FACTORS; PROGRAMMING
WINDOW; ALPHA-FETOPROTEIN; CRYPTORCHIDISM; HYPOSPADIAS; EPIDEMIOLOGY;
SERUM
AB The most consistently reported risk indicators for the male genital anomalies cryptorchidism and hypospadias are prematurity and low birth weight. Placental dysfunction has been hypothesized as a possible underlying cause, and an association between placental weight at birth and hypospadias has been indicated. In a population-based cohort of 388,422 Danish singleton boys born alive (1997-2008), we studied the association between placental weight and cryptorchidism and hypospadias. Missing data were handled with multiple imputation, and we estimated hazard ratios by means of Cox regression models. During follow-up, 1,713 boys were diagnosed with hypospadias and 6,878 with cryptorchidism (3,624 underwent corrective surgery). We observed an association between low placental weight and risk of both genital anomalies. Boys with a placental weight in the lowest decile (< 10%) had higher risks of both cryptorchidism (hazard ratio = 1.52, 95% confidence interval: 1.31, 1.76) and hypospadias (hazard ratio = 1.97, 95% confidence interval: 1.59, 2.45) than boys in the reference decile (50.0-59.9%). In conclusion, we found higher risks of both genital malformations in boys born with a low placental weight. The relationship seemed stronger for hypospadias than for cryptorchidism. Taken together, our data support a role for placental dysfunction in the etiology of these anomalies.
C1 [Arendt, Linn Hakonsen; Ramlau-Hansen, Cecilia Host; Olsen, Jorn] Aarhus Univ, Fac Hlth, Dept Publ Hlth, Epidemiol Sect, Bartholins Alle 2, DK-8000 Aarhus C, Denmark.
[Arendt, Linn Hakonsen; Henriksen, Tine Brink; Lindhard, Morten Sondergaard] Aarhus Univ Hosp, Dept Pediat, Perinatal Epidemiol Res Unit, Aarhus, Denmark.
[Wilcox, Allen J.] NIEHS, Epidemiol Branch, Durham, NC USA.
[Olsen, Jorn] Aarhus Univ Hosp, Dept Clin Epidemiol, Aarhus, Denmark.
RP Arendt, LH (reprint author), Aarhus Univ, Fac Hlth, Dept Publ Hlth, Epidemiol Sect, Bartholins Alle 2, DK-8000 Aarhus C, Denmark.
EM lha@ph.au.dk
RI Lindhard, Morten/B-1963-2008;
OI Lindhard, Morten/0000-0002-5685-8845; Wilcox, Allen/0000-0002-3376-1311
FU Faculty of Health, Aarhus University (Aarhus, Denmark)
FX This work was supported by a grant from the Faculty of Health, Aarhus
University (Aarhus, Denmark).
NR 41
TC 2
Z9 2
U1 0
U2 2
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0002-9262
EI 1476-6256
J9 AM J EPIDEMIOL
JI Am. J. Epidemiol.
PD JUN 15
PY 2016
VL 183
IS 12
BP 1122
EP 1128
DI 10.1093/aje/kwv336
PG 7
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA DR2IQ
UT WOS:000379728600008
PM 27257113
ER
PT J
AU Baldi, P
Przytycka, T
AF Baldi, Pierre
Przytycka, Teresa
TI ISMB 2016 Proceedings
SO BIOINFORMATICS
LA English
DT Editorial Material
C1 [Baldi, Pierre] Univ Calif Irvine, Dept Comp Sci, Irvine, CA 92697 USA.
[Przytycka, Teresa] NIH, Natl Ctr Biotechnol Informat, Bldg 10, Bethesda, MD 20892 USA.
RP Baldi, P (reprint author), Univ Calif Irvine, Dept Comp Sci, Irvine, CA 92697 USA.
OI Lopez, Rodrigo/0000-0003-1256-7306
NR 0
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1367-4803
EI 1460-2059
J9 BIOINFORMATICS
JI Bioinformatics
PD JUN 15
PY 2016
VL 32
IS 12
BP 1
EP 2
DI 10.1093/bioinformatics/btw326
PG 2
WC Biochemical Research Methods; Biotechnology & Applied Microbiology;
Computer Science, Interdisciplinary Applications; Mathematical &
Computational Biology; Statistics & Probability
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Computer Science; Mathematical & Computational Biology; Mathematics
GA DR2KV
UT WOS:000379734300001
ER
PT J
AU Wei, CH
Leaman, R
Lu, ZY
AF Wei, Chih-Hsuan
Leaman, Robert
Lu, Zhiyong
TI Beyond accuracy: creating interoperable and scalable text-mining web
services
SO BIOINFORMATICS
LA English
DT Article
ID NAMED ENTITY RECOGNITION; BIOMEDICAL LITERATURE; NORMALIZATION; SYSTEM
AB A Summary: The biomedical literature is a knowledge-rich resource and an important foundation for future research. With over 24 million articles in PubMed and an increasing growth rate, research in automated text processing is becoming increasingly important. We report here our recently developed web-based text mining services for biomedical concept recognition and normalization. Unlike most text-mining software tools, our web services integrate several state-of-the-art entity tagging systems (DNorm, GNormPlus, SR4GN, tmChem and tmVar) and offer a batch-processing mode able to process arbitrary text input (e.g. scholarly publications, patents and medical records) in multiple formats (e.g. BioC). We support multiple standards to make our service interoperable and allow simpler integration with other text-processing pipelines. To maximize scalability, we have preprocessed all PubMed articles, and use a computer cluster for processing large requests of arbitrary text.
C1 [Wei, Chih-Hsuan; Leaman, Robert; Lu, Zhiyong] Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA.
RP Lu, ZY (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA.
EM Zhiyong.Lu@nih.gov
FU NIH Intramural Research Program, National Library of Medicine
FX This research was supported by the NIH Intramural Research Program,
National Library of Medicine.
NR 27
TC 4
Z9 4
U1 2
U2 7
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1367-4803
EI 1460-2059
J9 BIOINFORMATICS
JI Bioinformatics
PD JUN 15
PY 2016
VL 32
IS 12
BP 1907
EP 1910
DI 10.1093/bioinformatics/btv760
PG 4
WC Biochemical Research Methods; Biotechnology & Applied Microbiology;
Computer Science, Interdisciplinary Applications; Mathematical &
Computational Biology; Statistics & Probability
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Computer Science; Mathematical & Computational Biology; Mathematics
GA DR2KV
UT WOS:000379734300069
PM 26883486
ER
PT J
AU Kamran, SC
de Gonzalez, AB
Ng, A
Haas-Kogan, D
Viswanathan, AN
AF Kamran, Sophia C.
de Gonzalez, Amy Berrington
Ng, Andrea
Haas-Kogan, Daphne
Viswanathan, Akila N.
TI Therapeutic radiation and the potential risk of second malignancies
SO CANCER
LA English
DT Review
DE carcinogenesis; neoplasm; radiotherapy; risk; second primary; survivors
ID CHILDHOOD-CANCER SURVIVOR; BRCA2 MUTATION CARRIERS; PRIMARY
BREAST-CANCER; HODGKINS-LYMPHOMA; IONIZING-RADIATION; ENDOMETRIAL
CANCER; NERVOUS-SYSTEM; LUNG-CANCER; SUBSEQUENT NEOPLASMS; CONTRALATERAL
BREAST
AB Radiation has long been associated with carcinogenesis. Nevertheless, it is an important part of multimodality therapy for many malignancies. It is critical to assess the risk of secondary malignant neoplasms (SMNs) after radiation treatment. The authors reviewed the literature with a focus on radiation and associated SMNs for primary hematologic, breast, gynecologic, and pediatric tumors. Radiation appeared to increase the risk of SMN in all of these; however, this risk was found to be associated with age, hormonal influences, chemotherapy use, environmental influences, genetic predisposition, infection, and immunosuppression. The risk also appears to be altered with modern radiotherapy techniques. Practitioners of all specialties who treat cancer survivors in follow-up should be aware of this potential risk. Cancer 2016;122:1809-21. (c) 2016 American Cancer Society.
Radiation appears to increase the risk of developing secondary neoplasms. This risk appears to be altered by multiple factors.
C1 [Kamran, Sophia C.] Harvard Univ, Sch Med, Harvard Radiat Oncol Program, Boston, MA USA.
[de Gonzalez, Amy Berrington] NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Ng, Andrea; Haas-Kogan, Daphne; Viswanathan, Akila N.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02115 USA.
RP Viswanathan, AN (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, 75 Francis St,ASB 1,L2, Boston, MA 02115 USA.
EM aviswanathan@lroc.harvard.edu
FU National Institutes of Health [R21 167800]
FX Akila N. Viswanathan is supported by National Institutes of Health grant
R21 167800.
NR 54
TC 1
Z9 1
U1 3
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0008-543X
EI 1097-0142
J9 CANCER-AM CANCER SOC
JI Cancer
PD JUN 15
PY 2016
VL 122
IS 12
BP 1809
EP 1821
DI 10.1002/cncr.29841
PG 13
WC Oncology
SC Oncology
GA DP3NR
UT WOS:000378402100007
PM 26950597
ER
PT J
AU Wills, AB
Spaulding, AB
Adjemian, J
Prevots, DR
Turk, SP
Williams, C
Marques, A
AF Wills, Aprielle B.
Spaulding, Alicen B.
Adjemian, Jennifer
Prevots, D. Rebecca
Turk, Siu-Ping
Williams, Carla
Marques, Adriana
TI Long-term Follow-up of Patients With Lyme Disease: Longitudinal Analysis
of Clinical and Quality-of-life Measures
SO CLINICAL INFECTIOUS DISEASES
LA English
DT Article
DE Borrelia burgdorferi; Lyme disease; epidemiology; quality of life;
longitudinal analysis
ID CONFIRMED ERYTHEMA MIGRANS; ACRODERMATITIS CHRONICA ATROPHICANS;
PERIPHERAL NEUROPATHY; ANTIBIOTIC-TREATMENT; DOUBLE-BLIND;
NEUROBORRELIOSIS; CEFTRIAXONE; BORRELIOSIS; OUTCOMES; MANIFESTATIONS
AB Background. Lyme disease is the most common vector-borne disease in the United States. Some patients report persistent or intermittent subjective symptoms of mild to moderate intensity after antibiotic treatment for Lyme disease. We sought to evaluate trends in clinical and quality-of-life (QOL) measures in a cohort of patients with Lyme disease enrolled in a natural history study at the National Institutes of Health from 2001-2014.
Methods. QOL was measured using the self-administered 36-item Short Form Health Survey (SF-36) during study follow-up. Primary outcomes included mean physical (PCS) and mental (MCS) health QOL composite scores and reporting long-term (>= 2 years) symptoms, adjusted for Lyme disease stage and severity at diagnosis.
Results. Overall, 101 patients with an average follow-up time of 3.9 years (range, 0.5-11.3 years) were included. At first visit, overall mean QOL scores were below the US population mean for both PCS (45.6 +/- 10.4) andMCS (47.3 +/- 11.5) but increased to just above the national average after 3 years of follow-up for both PCS (50.7 +/- 9.6) and MCS (50.1 +/- 10.0). Baseline QOL scores were lowest in those with late disease (P < 0.01) but also increased by the end of follow-up to national averages. In multivariate analysis, the only factors significantly associated with long-term symptoms or lower QOL scores were other comorbidities unrelated to Lyme disease.
Conclusions. Comorbid conditions can play a role in the reporting of long-term symptoms and overall QOL of Lyme disease patients and should be considered in the evaluation of these patients.
C1 [Wills, Aprielle B.; Spaulding, Alicen B.; Adjemian, Jennifer; Prevots, D. Rebecca] NIAID, Epidemiol Unit, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Wills, Aprielle B.; Spaulding, Alicen B.; Adjemian, Jennifer; Prevots, D. Rebecca; Turk, Siu-Ping; Marques, Adriana] NIAID, Lab Clin Infect Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Adjemian, Jennifer] US PHS, Commissioned Corps, Rockville, MD USA.
[Williams, Carla] NCI, Clin Monitoring Res Program, Leidos Biomed Res Inc, Frederick, MD 21701 USA.
RP Wills, AB (reprint author), NIAID, Epidemiol Unit, Lab Clin Infect Dis, NIH, 8 W Dr,Quarters 15B-1, Bethesda, MD 20892 USA.
EM aprielle.wills@nih.gov
FU Intramural Research Program of the National Institute of Allergy and
Infectious Diseases at the NIH; National Cancer Institute, Center for
Cancer Research, NIH [HHSN261200800001E]
FX This work was supported, in part, by the Intramural Research Program of
the National Institute of Allergy and Infectious Diseases at the NIH.
This project was funded, in part, with federal funds from the National
Cancer Institute, Center for Cancer Research, NIH (contract number
HHSN261200800001E).
NR 37
TC 5
Z9 6
U1 10
U2 16
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1058-4838
EI 1537-6591
J9 CLIN INFECT DIS
JI Clin. Infect. Dis.
PD JUN 15
PY 2016
VL 62
IS 12
BP 1546
EP 1551
DI 10.1093/cid/ciw189
PG 6
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA DP3ZL
UT WOS:000378434900012
PM 27025825
ER
PT J
AU Dropulic, LK
Ali, MA
Ombrello, AK
Cohen, JI
AF Dropulic, Lesia K.
Ali, Mir A.
Ombrello, Amanda K.
Cohen, Jeffrey I.
TI Periodic Illness Associated With Epstein-Barr Virus: A New Diagnosis
After a 22-Year Follow-up
SO CLINICAL INFECTIOUS DISEASES
LA English
DT Letter
ID ENCODING MEVALONATE KINASE; HYPERIMMUNOGLOBULINEMIA-D; FEVER SYNDROME;
PRIMARY IMMUNODEFICIENCIES; MUTATIONS; CHILD; IGD
C1 [Dropulic, Lesia K.; Ali, Mir A.; Cohen, Jeffrey I.] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
[Ombrello, Amanda K.] NHGRI, NIH, Bethesda, MD 20892 USA.
RP Cohen, JI (reprint author), NIH, Med Virol Sect, Infect Dis Lab, Bldg 50,Rm 6134, Bethesda, MD 20892 USA.
EM jcohen@niaid.nih.gov
NR 7
TC 0
Z9 0
U1 4
U2 4
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1058-4838
EI 1537-6591
J9 CLIN INFECT DIS
JI Clin. Infect. Dis.
PD JUN 15
PY 2016
VL 62
IS 12
BP 1613
EP U164
DI 10.1093/cid/ciw197
PG 2
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA DP3ZL
UT WOS:000378434900024
PM 27025823
ER
PT J
AU Pepper, DJ
Sun, JF
Welsh, J
Cui, XZ
Suffredini, AF
Eichacker, PQ
AF Pepper, Dominique J.
Sun, Junfeng
Welsh, Judith
Cui, Xizhong
Suffredini, Anthony F.
Eichacker, Peter Q.
TI Increased body mass index and adjusted mortality in ICU patients with
sepsis or septic shock: a systematic review and meta-analysis
SO CRITICAL CARE
LA English
DT Review
DE Sepsis; Obesity; Overweight; Body mass index; Mortality; Meta-analysis
ID INTENSIVE-CARE-UNIT; INTERNATIONAL MULTICENTER COHORT;
HIGH-DENSITY-LIPOPROTEINS; OBESITY PARADOX; CRITICALLY-ILL; DIFFICULT
INTUBATION; RETROSPECTIVE COHORT; HEIGHT ESTIMATION; ADIPOSE-TISSUE;
DEFINITIONS
AB Background: At least 25 % of adults admitted to intensive care units (ICU) in the United States have an overweight, obese or morbidly obese body mass index (BMI). The effect of BMI on adjusted mortality in adults requiring ICU treatment for sepsis is unclear. We performed a systematic review of adjusted all-cause mortality for underweight, overweight, obese and morbidly obese BMIs relative to normal BMI for adults admitted to the ICU with sepsis, severe sepsis, and septic shock.
Method: PubMed, the Cochrane Library, and EMBASE electronic databases were searched through November 18, 2015, without language restrictions. We included studies that reported multivariate regression analyses for all-cause mortality using standard BMI categories for adults admitted to the ICU for sepsis, severe sepsis, and septic shock. Articles were selected by consensus among multiple reviewers. Electronic database searches yielded 10,312 articles, of which six were eligible. Data were extracted by one reviewer and then reviewed by three independent reviewers. For the meta-analyses performed, the adjusted odds ratios (aOR) of mortality were combined using a random-effects model. Risk of bias was assessed using the Newcastle Ottawa quality assessment scale for cohort studies.
Results: Four retrospective (n = 6609 patients) and two prospective (n = 556) studies met inclusion criteria. Compared to normal BMI, across five studies each, overweight or obese BMIs reduced the adjusted odds ratio (95 % CI) of mortality [aOR] [0.83 (0.75, 0.91) p < 0.001 and 0.82 (0.67, 0.99) p = 0.04, respectively] with low or moderate heterogeneity (I-2 = 15.7 %, p = 0.31 and I-2 = 53.0 %, p = 0.07, respectively). Across three studies each, morbidly obese BMI and underweight BMI did not alter aOR [0.90 (0.59, 1.39), p = 0.64; I-2 = 43.3 %, p = 0.17; and 1.24 (0.79, 1.95), p = 0.35; I-2 = 15.6 %, p = 0.31 respectively]. Only one study clearly defined how and when height and weight measurements were calculated. Site of underlying infection and illness severity may have favored overweight and obese BMIs.
Conclusions: This is the first meta-analysis to show that overweight or obese BMIs reduce adjusted mortality in adults admitted to the ICU with sepsis, severe sepsis, or septic shock. More rigorous studies that address these limitations are needed to clarify the impact of BMI on sepsis ICU outcomes.
C1 [Pepper, Dominique J.; Sun, Junfeng; Cui, Xizhong; Suffredini, Anthony F.; Eichacker, Peter Q.] NIH, Dept Crit Care Med, Ctr Clin, Clin Ctr Bldg 10,Room 2C145,10 Ctr Dr, Bethesda, MD 20892 USA.
[Welsh, Judith] NIH, Natl Inst Hlth Lib, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA.
RP Pepper, DJ (reprint author), NIH, Dept Crit Care Med, Ctr Clin, Clin Ctr Bldg 10,Room 2C145,10 Ctr Dr, Bethesda, MD 20892 USA.
EM dominique.pepper@nih.gov
FU National Institutes of Health Clinical Center
FX The National Institutes of Health Clinical Center supported this work.
NR 62
TC 2
Z9 2
U1 5
U2 5
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1466-609X
EI 1364-8535
J9 CRIT CARE
JI Crit. Care
PD JUN 15
PY 2016
VL 20
AR 181
DI 10.1186/s13054-016-1360-z
PG 10
WC Critical Care Medicine
SC General & Internal Medicine
GA DP5VX
UT WOS:000378567400001
PM 27306751
ER
PT J
AU Marzahn, MR
Marada, S
Lee, J
Nourse, A
Kenrick, S
Zhao, HY
Ben-Nissan, G
Kolaitis, RM
Peters, JL
Pounds, S
Errington, WJ
Prive, GG
Taylor, JP
Sharon, M
Schuck, P
Ogden, SK
Mittag, T
AF Marzahn, Melissa R.
Marada, Suresh
Lee, Jihun
Nourse, Amanda
Kenrick, Sophia
Zhao, Huaying
Ben-Nissan, Gili
Kolaitis, Regina-Maria
Peters, Jennifer L.
Pounds, Stanley
Errington, Wesley J.
Prive, Gilbert G.
Taylor, J. Paul
Sharon, Michal
Schuck, Peter
Ogden, Stacey K.
Mittag, Tanja
TI Higher-order oligomerization promotes localization of SPOP to liquid
nuclear speckles
SO EMBO JOURNAL
LA English
DT Article
DE isodesmic self-association; membrane-less organelle; prostate cancer;
speckle-type POZ protein; ubiquitin ligase
ID STATIC LIGHT-SCATTERING; UBIQUITIN LIGASE COMPLEX; PROTEIN
SELF-ASSOCIATION; PROSTATE-CANCER; QUANTITATIVE CHARACTERIZATION;
SEDIMENTATION-VELOCITY; ENDOPLASMIC-RETICULUM; PHASE-TRANSITIONS;
UNFOLDED PROTEIN; EQUILIBRIUM
AB Membrane-less organelles in cells are large, dynamic protein/protein or protein/RNA assemblies that have been reported in some cases to have liquid droplet properties. However, the molecular interactions underlying the recruitment of components are not well understood. Herein, we study how the ability to form higher-order assemblies influences the recruitment of the speckle-type POZ protein (SPOP) to nuclear speckles. SPOP, a cullin-3-RING ubiquitin ligase (CRL3) substrate adaptor, self-associates into higher-order oligomers; that is, the number of monomers in an oligomer is broadly distributed and can be large. While wild-type SPOP localizes to liquid nuclear speckles, self-association-deficient SPOP mutants have a diffuse distribution in the nucleus. SPOP oligomerizes through its BTB and BACK domains. We show that BTB-mediated SPOP dimers form linear oligomers via BACK domain dimerization, and we determine the concentration-dependent populations of the resulting oligomeric species. Higher-order oligomerization of SPOP stimulates CRL3(SPOP) ubiquitination efficiency for its physiological substrate Gli3, suggesting that nuclear speckles are hotspots of ubiquitination. Dynamic, higher-order protein self-association may be a general mechanism to concentrate functional components in membrane-less cellular bodies.
C1 [Marzahn, Melissa R.; Lee, Jihun; Mittag, Tanja] St Jude Childrens Res Hosp, Dept Biol Struct, 332 N Lauderdale St, Memphis, TN 38105 USA.
[Marada, Suresh; Kolaitis, Regina-Maria; Ogden, Stacey K.] St Jude Childrens Res Hosp, Dept Cell & Mol Biol, 332 N Lauderdale St, Memphis, TN 38105 USA.
[Nourse, Amanda] St Jude Childrens Res Hosp, Mol Interact Anal Shared Resource, 332 N Lauderdale St, Memphis, TN 38105 USA.
[Kenrick, Sophia] Wyatt Technol Corp, Santa Barbara, CA USA.
[Zhao, Huaying; Schuck, Peter] Natl Inst Biomed Imaging & Bioengn, Dynam Macromol Assembly Sect, Lab Cellular Imaging & Macromol Biophys, NIH, Bethesda, MD USA.
[Ben-Nissan, Gili; Sharon, Michal] Weizmann Inst Sci, Dept Biol Chem, IL-76100 Rehovot, Israel.
[Peters, Jennifer L.] St Jude Childrens Res Hosp, Dept Cellular Imaging Shared Resource, 332 N Lauderdale St, Memphis, TN 38105 USA.
[Pounds, Stanley] St Jude Childrens Res Hosp, Dept Biostat, 332 N Lauderdale St, Memphis, TN 38105 USA.
[Errington, Wesley J.; Prive, Gilbert G.] Univ Toronto, Dept Biochem, Toronto, ON, Canada.
[Prive, Gilbert G.] Princess Margaret Canc Ctr, Toronto, ON, Canada.
[Taylor, J. Paul] St Jude Childrens Res Hosp, Howard Hughes Med Inst, Dept Cell & Mol Biol, 332 N Lauderdale St, Memphis, TN 38105 USA.
[Errington, Wesley J.] Univ Minnesota, Dept Biomed Engn, Minneapolis, MN USA.
RP Mittag, T (reprint author), St Jude Childrens Res Hosp, Dept Biol Struct, 332 N Lauderdale St, Memphis, TN 38105 USA.; Ogden, SK (reprint author), St Jude Childrens Res Hosp, Dept Cell & Mol Biol, 332 N Lauderdale St, Memphis, TN 38105 USA.
EM stacey.ogden@stjude.org; tanja.mittag@stjude.org
OI Sharon, Michal/0000-0003-3933-0595
FU V Foundation Scholar Grant [R01GM112846, R01GM101087]; National Cancer
Institute Cancer Center Support Grant (St. Jude Children's Research
Hospital) [P30CA21765]; American Lebanese Syrian Associated Charities;
Intramural Program of the National Institute of Biomedical Imaging and
Bioengineering
FX We thank BA Schulman, WK Pierce, EW Martin, and CR Grace for valuable
discussions and N Clark for preliminary data collection. We also thank H
Haecker (St. Jude Children's Research Hospital). This work was funded by
a V Foundation Scholar Grant (T.M.), R01GM112846 (T.M.), R01GM101087
(S.K.O.), the National Cancer Institute Cancer Center Support Grant
P30CA21765 (at St. Jude Children's Research Hospital), the American
Lebanese Syrian Associated Charities (to J.P.T., S.K.O., and T.M.), and
the Intramural Program of the National Institute of Biomedical Imaging
and Bioengineering (P.S.). Microscopy images were acquired at the Cell &
Tissue Imaging Center at St. Jude Children's Research Hospital.
NR 73
TC 1
Z9 1
U1 8
U2 12
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0261-4189
EI 1460-2075
J9 EMBO J
JI Embo J.
PD JUN 15
PY 2016
VL 35
IS 12
BP 1254
EP 1275
DI 10.15252/embj.201593169
PG 22
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA DQ0ZC
UT WOS:000378929300002
PM 27220849
ER
PT J
AU Espana, RA
Schmeichel, BE
Berridge, CW
AF Espana, Rodrigo A.
Schmeichel, Brooke E.
Berridge, Craig W.
TI Norepinephrine at the nexus of arousal, motivation and relapse
SO BRAIN RESEARCH
LA English
DT Review
DE Stimulants; Addiction; Amphetamine; Catecholamines; Noradrenergic; Locus
coeruleus
ID DOPAMINE-BETA-HYDROXYLASE; COCAINE-INDUCED REINSTATEMENT; STRESS-INDUCED
REINSTATEMENT; MEDIAL PREOPTIC AREA; CORTICOTROPIN-RELEASING-FACTOR;
CONDITIONED PLACE PREFERENCE; LOCUS-COERULEUS NEURONS; WAKE-PROMOTING
ACTIONS; POSITIVE REINFORCING PROPERTIES; HALOTHANE-ANESTHETIZED RAT
AB Arousal plays a critical role in cognitive, affective and motivational processes. Consistent with this, the dysregulation of arousal-related neural systems is implicated in a variety of psychiatric disorders, including addiction. Noradrenergic systems exert potent arousal enhancing actions that involve signaling at alpha(1)- and (beta-noradrenergic receptors within a distributed network of subcortical regions. The majority of research into noradrenergic modulation of arousal has focused on the nucleus locus coeruleus. Nevertheless, anatomical studies demonstrate that multiple noradrenergic nuclei innervate subcortical arousal-related regions, providing a substrate for differential regulation of arousal across these distinct noradrenergic nuclei. The arousal-promoting actions of psychostimulants and other drugs of abuse contribute to their widespread abuse. Moreover, relapse can be triggered by a variety of arousal-promoting events, including stress and re-exposure to drugs of abuse. Evidence has long-indicated that norepinephrine plays an important role in relapse. Recent observations suggest that noradrenergic signaling elicits affectively-neutral arousal that is sufficient to reinstate drug seeking. Collectively, these observations indicate that norepinephrine plays a key role in the interaction between arousal, motivation, and relapse. This article is part of a Special Issue entitled SI: Noradrenergic System. (C) 2016 Elsevier B.V. All rights reserved.
C1 [Espana, Rodrigo A.] Drexel Univ, Coll Med, Dept Neurobiol & Anat, Philadelphia, PA 19104 USA.
[Schmeichel, Brooke E.] NIDA, Intramural Res Program, Baltimore, MD USA.
[Berridge, Craig W.] Univ Wisconsin, Dept Psychol, 1202 W Johnson St, Madison, WI 53706 USA.
RP Espana, RA (reprint author), Drexel Univ, Coll Med, Dept Neurobiol & Anat, Philadelphia, PA 19104 USA.
EM respana@drexelmed.edu; brooke.schmeichel@nih.gov; berridge@wisc.edu
FU PHS [DA10681, DA00389, MH081843, DA031900]; University of Wisconsin
Graduate School; National Institute on Drug Abuse
FX This work was supported by PHS grants DA10681, DA00389, MH081843,
DA031900, the University of Wisconsin Graduate School, and the National
Institute on Drug Abuse, Intramural Research Program. The authors
declare no conflict of interest.
NR 106
TC 2
Z9 2
U1 1
U2 3
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0006-8993
EI 1872-6240
J9 BRAIN RES
JI Brain Res.
PD JUN 15
PY 2016
VL 1641
SI SI
BP 207
EP 216
DI 10.1016/j.brainres.2016.01.002
PN B
PG 10
WC Neurosciences
SC Neurosciences & Neurology
GA DP4ED
UT WOS:000378448100006
PM 26773688
ER
PT J
AU Robertson, SD
Plummer, NW
Jensen, P
AF Robertson, Sabrina D.
Plummer, Nicholas W.
Jensen, Patricia
TI Uncovering diversity in the development of central noradrenergic neurons
and their efferents
SO BRAIN RESEARCH
LA English
DT Article
DE Norepinephrine; Hoxb1; Fate map; Recombinase-based intersectional;
genetic fate mapping; Efferents; Rhombomere
ID ACID RESPONSE ELEMENT; HOXA2 MUTANT MICE; HINDBRAIN; SYSTEM;
PROJECTIONS; EXPRESSION; HOXB-1; NOREPINEPHRINE; ORGANIZATION;
CEREBELLUM
AB Uncovering the mechanisms that underlie central noradrenergic neuron heterogeneity is essential to understanding selective subtype vulnerability to disease and environmental insult. Using recombinase-based intersectional genetic fate mapping we have previously demonstrated that molecularly distinct progenitor populations give rise to mature noradrenergic neurons differing in their anatomical location, axon morphology and efferent projection pattern. Here we review the findings from our previous study and extend our analysis of the noradrenergic subpopulation defined by transient developmental expression of Hoxb1. Using a combination of intersectional genetic fate mapping and analysis of a targeted loss of function mutation in Hoxb1, we have now uncovered additional heterogeneity based on the requirement of some noradrenergic neurons for Hoxb1 expression. By comparing the distribution of noradrenergic neurons derived from the Hoxb1 expression domain in wild-type and mutant mice, we demonstrate that Hoxb1 expression is required by a subset of neurons in the pons. Additional fate mapping, using a Hoxb1 enhancer element that drives Cre recombinase expression exclusively in rhombomere 4 of the hindbrain, reveals the existence of a subpopulation of noradrenergic neurons in the pons with more restricted axonal targets than the full Hoxb1-derived subpopulation. The unique projection profile of this newly defined subpopulation suggests that it may be functionally distinct. These analyses shed new light on the molecular determinants of noradrenergic identity in the pons and the overall complexity of the central noradrenergic system. This article is part of a Special Issue entitled SI: Noradrenergic System. Published by Elsevier B.V.
C1 [Plummer, Nicholas W.; Jensen, Patricia] NIEHS, Neurobiol Lab, NIH, US Dept HHS, POB 12233, Res Triangle Pk, NC 27709 USA.
[Robertson, Sabrina D.] N Carolina State Univ, Biotechnol Program, Dept Mol & Biomed Sci, Raleigh, NC 27695 USA.
RP Jensen, P (reprint author), NIEHS, Neurobiol Lab, NIH, US Dept HHS, POB 12233, Res Triangle Pk, NC 27709 USA.
EM Patricia.jensen@nih.gov
OI Robertson, Sabrina/0000-0003-4598-6929
FU NIH, National Institute of Environmental Health Sciences [ZIA-ES-102805]
FX We thank Dr. S. Dymecki for RC::FrePe mice. We thank T. Wolfgang, G.
Keeley and NIEHS Fluorescence Microscopy, Vivarium, Knockout Mice, and
Statistics services for assistance. This research was supported by the
Intramural Research Program of the NIH, National Institute of
Environmental Health Sciences (ZIA-ES-102805).
NR 29
TC 0
Z9 0
U1 1
U2 1
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0006-8993
EI 1872-6240
J9 BRAIN RES
JI Brain Res.
PD JUN 15
PY 2016
VL 1641
SI SI
BP 234
EP 244
DI 10.1016/j.brainres.2015.11.023
PN B
PG 11
WC Neurosciences
SC Neurosciences & Neurology
GA DP4ED
UT WOS:000378448100008
PM 26612521
ER
PT J
AU Mejias-Aponte, CA
AF Mejias-Aponte, Carlos A.
TI Specificity and impact of adrenergic projections to the midbrain
dopamine system
SO BRAIN RESEARCH
LA English
DT Review
DE Norepinephrine; Dopamine; Anatomy; Physiology; Addiction; Prefrontal
cortex
ID VENTRAL TEGMENTAL AREA; FREELY MOVING RATS; RECEPTOR MESSENGER-RNA;
CURRENT I-H; PREFRONTAL CORTEX; NUCLEUS-ACCUMBENS; EXTRACELLULAR
DOPAMINE; LOCUS-COERULEUS; BETA-HYDROXYLASE; SUBSTANTIA-NIGRA
AB Dopamine (DA) is a neuromodulator that regulates different brain circuits involved in cognitive functions, motor coordination, and emotions. Dysregulation of DA is associated with many neurological and psychiatric disorders such as Parkinson's disease and substance abuse. Several lines of research have shown that the midbrain DA system is regulated by the central adrenergic system. This review focuses on adrenergic interactions with midbrain DA neurons. It discusses the current neuroanatomy including source of adrenergic innervation, type of synapses, and adrenoceptors expression. It also discusses adrenergic regulation of DA cell activity and neurotransmitter release. Finally, it reviews several neurological and psychiatric disorders where changes in adrenergic system are associated with dysregulation of the midbrain DA system. This article is part of a Special Issue entitled SI: Noradrenergic System. (C) 2016 Elsevier B.V. All rights reserved.
C1 [Mejias-Aponte, Carlos A.] NIDA, Histol Core, Neuronal Networks Sect, Integrat Neurosci Res Branch,Biomed Res Ctr, 251 Bayview Blvd,Suite 200, Baltimore, MD 21224 USA.
RP Mejias-Aponte, CA (reprint author), NIDA, Histol Core, Neuronal Networks Sect, Integrat Neurosci Res Branch,Biomed Res Ctr, 251 Bayview Blvd,Suite 200, Baltimore, MD 21224 USA.
EM mejiasca@mail.nih.gov
FU National Institute on Drug Abuse
FX Research is supported by the National Institute on Drug Abuse Intramural
Research Program. My gratitude goes to Vadim Kashtelyan, Gustavo
Mejias-Torres and David Barker for proofreading the manuscript and
providing edits to improve its readability.
NR 152
TC 1
Z9 1
U1 10
U2 13
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0006-8993
EI 1872-6240
J9 BRAIN RES
JI Brain Res.
PD JUN 15
PY 2016
VL 1641
SI SI
BP 258
EP 273
DI 10.1016/j.brainres.2016.01.036
PN B
PG 16
WC Neurosciences
SC Neurosciences & Neurology
GA DP4ED
UT WOS:000378448100010
PM 26820641
ER
PT J
AU Citrin, DE
AF Citrin, Deborah E.
TI Short-Term Screening Assays for the Identification of Therapeutics for
Cancer
SO CANCER RESEARCH
LA English
DT Editorial Material
ID HELA CELLS; INHIBITOR; INVITRO
C1 [Citrin, Deborah E.] NIH, Radiat Oncol Branch, Ctr Canc Res, Bldg 10, Bethesda, MD 20892 USA.
RP Citrin, DE (reprint author), NCI, Bldg 10,Hatfield CRC,B2-3500, Bethesda, MD 20892 USA.
EM citrind@mail.nih.gov
NR 13
TC 1
Z9 1
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD JUN 15
PY 2016
VL 76
IS 12
BP 3443
EP 3445
DI 10.1158/0008-5472.CAN-16-1299
PG 3
WC Oncology
SC Oncology
GA DO8VN
UT WOS:000378063200002
PM 27306870
ER
PT J
AU Basiorka, AA
McGraw, KL
De Ceuninck, L
Griner, LN
Zhang, L
Clark, JA
Caceres, G
Sokol, L
Komrokji, RS
Reuther, GW
Wei, S
Tavernier, J
List, AF
AF Basiorka, Ashley A.
McGraw, Kathy L.
De Ceuninck, Leentje
Griner, Lori N.
Zhang, Ling
Clark, Justine A.
Caceres, Gisela
Sokol, Lubomir
Komrokji, Rami S.
Reuther, Gary W.
Wei, Sheng
Tavernier, Jan
List, Alan F.
TI Lenalidomide Stabilizes the Erythropoietin Receptor by Inhibiting the E3
Ubiquitin Ligase RNF41
SO CANCER RESEARCH
LA English
DT Article
ID MYELODYSPLASTIC SYNDROMES; THALIDOMIDE TERATOGENICITY; CELLS;
DEGRADATION; CYTOKINE; DIFFERENTIATION
AB In a subset of patients with non-del(5q) myelodysplastic syndrome (MDS), lenalidomide promotes erythroid lineage competence and effective erythropoiesis. To determine the mechanism by which lenalidomide promotes erythropoiesis, we investigated its action on erythropoietin receptor (EpoR) cellular dynamics. Lenalidomide upregulated expression and stability of JAK2-associated EpoR in UT7 erythroid cells and primary CD71+ erythroid progenitors. The effects of lenalidomide on receptor turnover were Type I cytokine receptor specific, as evidenced by coregulation of the IL3-R alpha receptor but not c-Kit. To elucidate this mechanism, we investigated the effects of lenalidomide on the E3 ubiquitin ligase RNF41. Lenalidomide promoted EpoR/RNF41 association and inhibited RNF41 auto-ubiquitination, accompanied by a reduction in EpoR ubiquitination. To confirm that RNF41 is the principal target responsible for EpoR stabilization, HEK293T cells were transfected with EpoR and/or RNF41 gene expression vectors. Steady-state EpoR expression was reduced in EpoR/RNF41 cells, whereas EpoR upregulation by lenalidomide was abrogated, indicating that cellular RNF41 is a critical determinant of drug-induced receptor modulation. Notably, shRNA suppression of CRBN gene expression failed to alter EpoR upregulation, indicating that drug-induced receptor modulation is independent of cereblon. Immunohistochemical staining showed that RNF41 expression decreased in primary erythroid cells of lenalidomide-responding patients, suggesting that cellular RNF41 expression merits investigation as a biomarker for lenalidomide response. Our findings indicate that lenalidomide has E3 ubiquitin ligase inhibitory effects that extend to RNF41 and that inhibition of RNF41 auto-ubiquitination promotes membrane accumulation of signaling competent JAK2/EpoR complexes that augment Epo responsiveness. (C) 2016 AACR.
C1 [Basiorka, Ashley A.; McGraw, Kathy L.; Clark, Justine A.; Sokol, Lubomir; Komrokji, Rami S.; List, Alan F.] Univ S Florida, H Lee Moffitt Canc Ctr, Dept Malignant Hematol, Tampa, FL 33682 USA.
[Basiorka, Ashley A.] Univ S Florida, Canc Biol PhD Program, Tampa, FL USA.
[De Ceuninck, Leentje; Tavernier, Jan] Univ Ghent, VIB Dept Med Prot Res, Ghent, Belgium.
[Griner, Lori N.] NICHHD, NIH, Bethesda, MD 20892 USA.
[Zhang, Ling] Univ S Florida, H Lee Moffitt Canc Ctr, Dept Hematopathol, Tampa, FL 33682 USA.
[Caceres, Gisela] Univ S Florida, H Lee Moffitt Canc Ctr, Morsani Mol Diagnost Lab, Tampa, FL 33682 USA.
[Reuther, Gary W.] Univ S Florida, H Lee Moffitt Canc Ctr, Dept Mol Oncol, Tampa, FL 33682 USA.
[Wei, Sheng] Univ S Florida, H Lee Moffitt Canc Ctr, Dept Immunol, Tampa, FL 33682 USA.
RP List, AF (reprint author), SRB CEO, 12902 Magnolia Dr, Tampa, FL 33612 USA.
EM Alan.List@Moffitt.org
FU National Cancer Institute/NIH [5 R01 CA131076-04]; Belgian government
[IUAP P6/36]; Group-ID Multidisciplinary Research Partnership of Ghent
University; ERC Advanced Grant [340941]
FX Support for this work was provided by the National Cancer Institute/NIH
(5 R01 CA131076-04) and by grants from the Belgian government (IUAP
P6/36) and the Group-ID Multidisciplinary Research Partnership of Ghent
University. J. Tavernier holds an ERC Advanced Grant (No 340941).
NR 30
TC 2
Z9 2
U1 5
U2 6
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD JUN 15
PY 2016
VL 76
IS 12
BP 3531
EP 3540
DI 10.1158/0008-5472.CAN-15-1756
PG 10
WC Oncology
SC Oncology
GA DO8VN
UT WOS:000378063200011
PM 27197154
ER
PT J
AU Zhou, BY
Wang, L
Zhang, S
Bennett, BD
He, F
Zhang, Y
Xiong, CL
Han, L
Diao, LX
Li, PS
Fargo, DC
Cox, AD
Hu, G
AF Zhou, Bingying
Wang, Li
Zhang, Shu
Bennett, Brian D.
He, Fan
Zhang, Yan
Xiong, Chengliang
Han, Leng
Diao, Lixia
Li, Pishun
Fargo, David C.
Cox, Adrienne D.
Hu, Guang
TI INO80 governs superenhancer-mediated oncogenic transcription and tumor
growth in melanoma
SO GENES & DEVELOPMENT
LA English
DT Article
DE INO80; chromatin remodeler; oncogenic transcription; superenhancer
ID SUPER-ENHANCERS; REGULATORY REGIONS; CELL IDENTITY; CHROMATIN; CANCER;
MUTATIONS; LANDSCAPE; DIFFERENTIATION; EPIGENETICS; INHIBITION
AB Superenhancers (SEs) are large genomic regions with a high density of enhancer marks. In cancer, SEs are found near oncogenes and dictate cancer gene expression. However, how oncogenic SEs are regulated remains poorly understood. Here, we show that INO80, achromatin remodeling complex, is required for SE-mediated oncogenic transcription and tumor growth in melanoma. The expression of Ino80, the SWI/SNFATPase, is elevated in melanoma cells and patient melanomas compared with normal melanocytes and benign nevi. Furthermore, Ino80 silencing selectively inhibits melanoma cell proliferation, anchorage-independent growth, tumorigenesis, and tumor maintenance in mouse xenografts. Mechanistically, Ino80 occupies >90% of SEs, and its occupancy is dependent on transcription factors such as MITF and Sox9. Ino80 binding reduces nucleosome occupancy and facilitates Mediator recruitment, thus promoting oncogenic transcription. Consistently, genes co-occupied by Ino80 and Med1 are selectively expressed in melanomas compared with melanocytes. Together, our results reveal an essential role of INO80-dependent chromatin remodeling in SE function and suggest a novel strategy for disrupting SEs in cancer treatment.
C1 [Zhou, Bingying; Wang, Li] Chinese Acad Med Sci, Natl Ctr Cardiovasc Dis, Fuwai Hosp, State Key Lab Cardiovasc Dis, Beijing 100037, Peoples R China.
[Zhou, Bingying; Wang, Li] Peking Union Med Coll, Beijing 100037, Peoples R China.
[Zhou, Bingying; Cox, Adrienne D.] Univ N Carolina, Dept Pharmacol, Chapel Hill, NC 27599 USA.
[Zhou, Bingying; Cox, Adrienne D.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA.
[Wang, Li; Li, Pishun; Hu, Guang] NIEHS, Epigenet & Stem Cell Biol Lab, POB 12233, Res Triangle Pk, NC 27709 USA.
[Zhang, Shu] Chinese Peoples Liberat Army Gen Hosp, Dept Pulm & Crit Care Med, Beijing 100853, Peoples R China.
[Bennett, Brian D.; Fargo, David C.] NIEHS, Integrat Bioinformat, POB 12233, Res Triangle Pk, NC 27709 USA.
[He, Fan] Huazhong Univ Sci & Technol, Tongji Med Coll, Tongji Hosp, Dept Nephrol, Wuhan 430030, Hubei, Peoples R China.
[Zhang, Yan; Xiong, Chengliang] Huazhong Univ Sci & Technol, Tongji Med Coll, Ctr Reprod Med, Family Planning Res Inst, Wuhan 430030, Hubei, Peoples R China.
[Han, Leng] Univ Texas Hlth Sci Ctr Houston, Dept Biochem & Mol Biol, McGovern Med Sch, Houston, TX 77030 USA.
[Diao, Lixia] Univ Texas MD Anderson Canc Ctr, Dept Bioinformat & Computat Biol, Houston, TX 77030 USA.
[Cox, Adrienne D.] Univ N Carolina, Dept Radiat Oncol, Chapel Hill, NC 27599 USA.
RP Wang, L (reprint author), Chinese Acad Med Sci, Natl Ctr Cardiovasc Dis, Fuwai Hosp, State Key Lab Cardiovasc Dis, Beijing 100037, Peoples R China.; Wang, L (reprint author), Peking Union Med Coll, Beijing 100037, Peoples R China.; Cox, AD (reprint author), Univ N Carolina, Dept Pharmacol, Chapel Hill, NC 27599 USA.; Cox, AD (reprint author), Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA.; Wang, L; Hu, G (reprint author), NIEHS, Epigenet & Stem Cell Biol Lab, POB 12233, Res Triangle Pk, NC 27709 USA.; Cox, AD (reprint author), Univ N Carolina, Dept Radiat Oncol, Chapel Hill, NC 27599 USA.
EM wangl@pumc.edu.cn; adrienne_cox@med.unc.edu; hug4@niehs.nih.gov
FU Intramural Research Program of the National Institutes of Health, the
National Institute of Environmental Health Sciences [Z01ES102745];
National Institutes of Health [CA042978, CA161494]
FX We thank the Epigenomics core facility at National Institute of
Environmental Health Sciences for providing the Illumina sequencing
services. This study was supported in part by the Intramural Research
Program of the National Institutes of Health, the National Institute of
Environmental Health Sciences (Z01ES102745 to G.H.) and National
Institutes of Health grants CA042978 and CA161494 (to A.D.C.). B.Z.,
L.W., A.D.C., and G.H. designed the experiments. B.Z. and L.W. carried
out the experiments in melanoma cell lines. L.W. and S.Z. carried out
animal experiments. F.H., Y.Z., and C.X. carried out experiments in
patient samples. L.W. and P.L. carried out genomic experiments. B.B.,
D.F., L.H., and L.D. carried out bioinformatics analysis. B.Z., L.W.,
A.D.C., and G.H. interpreted the data and wrote the manuscript.
NR 41
TC 1
Z9 1
U1 6
U2 11
PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
PI COLD SPRING HARBOR
PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA
SN 0890-9369
EI 1549-5477
J9 GENE DEV
JI Genes Dev.
PD JUN 15
PY 2016
VL 30
IS 12
BP 1440
EP 1453
DI 10.1101/gad.277178.115
PG 14
WC Cell Biology; Developmental Biology; Genetics & Heredity
SC Cell Biology; Developmental Biology; Genetics & Heredity
GA DP5JV
UT WOS:000378533000007
PM 27340176
ER
PT J
AU Chao, FA
Byrd, RA
AF Chao, Fa-An
Byrd, R. Andrew
TI Geometric Approximation: A New Computational Approach To Characterize
Protein Dynamics from NMR Adiabatic Relaxation Dispersion Experiments
SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Article
ID NUCLEAR-MAGNETIC-RESONANCE; CONFORMATIONAL DYNAMICS; R-1-RHO RELAXATION;
FAST-EXCHANGE; UBIQUITINATION; ACTIVATION; RECOGNITION; CATALYSIS;
MOTIONS; PULSES
AB A new computational strategy is reported that provides a fast approximation of numerical solutions of differential equations in general. The method is demonstrated with the analysis of NMR adiabatic relaxation dispersion experiments to reveal biomolecular dynamics. When an analytical solution to the theoretical equations describing a physical process is not available, the new approach can significantly accelerate the computational speed of the conventional numerical integration up to 10(5) times. NMR adiabatic relaxation dispersion experiments enhanced with optimized proton-decoupled pulse sequences, although extremely powerful, have previously been refractory to quantitative analysis. Both simulations and experimental validation demonstrate detectable "slow" (microsecond to millisecond) conformational exchange rates from 10(2) to 10(5) s(-1). This greatly expanded time-scale range enables the characterization of a wide array of conformational fluctuations for individual residues, which correlate with biomolecular function and were previously inaccessible. Moreover, the new computational method can be potentially generalized for analysis of new types of relaxation dispersion experiments to characterize the various dynamics of biomolecular systems.
C1 [Chao, Fa-An; Byrd, R. Andrew] NCI, Struct Biophys Lab, Ctr Canc Res, Frederick, MD 21702 USA.
RP Chao, FA; Byrd, RA (reprint author), NCI, Struct Biophys Lab, Ctr Canc Res, Frederick, MD 21702 USA.
EM fa-an.chao@nih.gov; byrdra@mail.nih.gov
OI Byrd, R. Andrew/0000-0003-3625-4232
FU Intramural Research Program of the National Cancer Institute
FX This work was supported by the Intramural Research Program of the
National Cancer Institute. We thank Prof. Gianluigi Veglia and Dr.
Youlin Xia (University of Minnesota) for providing the original
sequences of the adiabatic spin-lock experiments, Prof. Nathaniel J.
Traaseth (New York University) for inspirational discussions, and Dr.
Michelle L. Gill for technical support and discussions. The biological
samples were provided by Ms. Jess Li.
NR 34
TC 2
Z9 2
U1 5
U2 7
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0002-7863
J9 J AM CHEM SOC
JI J. Am. Chem. Soc.
PD JUN 15
PY 2016
VL 138
IS 23
BP 7337
EP 7345
DI 10.1021/jacs.6b02786
PG 9
WC Chemistry, Multidisciplinary
SC Chemistry
GA DP0QC
UT WOS:000378193300025
PM 27225523
ER
PT J
AU Singleton, A
Hardy, J
AF Singleton, Andrew
Hardy, John
TI The Evolution of Genetics: Alzheimer's and Parkinson's Diseases
SO NEURON
LA English
DT Review
ID GENOME-WIDE ASSOCIATION; COMMON VARIANTS; RISK LOCI; IDENTIFIES
VARIANTS; MISSENSE MUTATIONS; SEQUENCE VARIANTS; SUSCEPTIBILITY;
METAANALYSIS; PATHWAY; COMPLEX
AB Genetic discoveries underlie the majority of the current thinking in neurodegenerative disease. This work has been driven by the significant gains made in identifying causal mutations; however, the translation of genetic causes of disease into pathobiological understanding remains a challenge. The application of a second generation of genetics methods allows the dissection of moderate and mild genetic risk factors for disease. This requires new thinking in two key areas: what constitutes proof of pathogenicity, and how do we translate these findings to biological understanding. Here we describe the progress and ongoing evolution in genetics. We describe a view that rejects the tradition that genetic proof has to be absolute before functional characterization and centers on a multi-dimensional approach integrating genetics, reference data, and functional work. We also argue that these challenges cannot be efficiently met by traditional hypothesis-driven methods but that high content system-wide efforts are required.
C1 [Singleton, Andrew; Hardy, John] NIA, Lab Neurogenet, Bethesda, MD 20892 USA.
RP Singleton, A (reprint author), NIA, Lab Neurogenet, Bethesda, MD 20892 USA.
EM singleta@mail.nih.gov
RI Singleton, Andrew/C-3010-2009; Hardy, John/C-2451-2009
FU Intramural Research Program of the National Institute on Aging, National
Institutes of Health, Department of Health and Human Services [ZO1
AG000949]
FX This work was supported in part by the Intramural Research Program of
the National Institute on Aging, National Institutes of Health,
Department of Health and Human Services; project ZO1 AG000949.
NR 62
TC 5
Z9 5
U1 22
U2 40
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0896-6273
EI 1097-4199
J9 NEURON
JI Neuron
PD JUN 15
PY 2016
VL 90
IS 6
BP 1154
EP 1163
DI 10.1016/j.neuron.2016.05.040
PG 10
WC Neurosciences
SC Neurosciences & Neurology
GA DP5HT
UT WOS:000378527600006
PM 27311081
ER
PT J
AU Gremel, CM
Chancey, JH
Atwood, BK
Luo, GX
Neve, R
Ramakrishnan, C
Deisseroth, K
Lovinger, DM
Costa, RM
AF Gremel, Christina M.
Chancey, Jessica H.
Atwood, Brady K.
Luo, Guoxiang
Neve, Rachael
Ramakrishnan, Charu
Deisseroth, Karl
Lovinger, David M.
Costa, Rui M.
TI Endocannabinoid Modulation of Orbitostriatal Circuits Gates Habit
Formation
SO NEURON
LA English
DT Article
ID OBSESSIVE-COMPULSIVE DISORDER; GOAL-DIRECTED BEHAVIOR; ORBITOFRONTAL
CORTEX; DORSAL STRIATUM; DORSOLATERAL STRIATUM; PREFRONTAL CORTEX;
REINFORCER DEVALUATION; CANNABINOID RECEPTORS; DORSOMEDIAL STRIATUM;
SYNAPTIC MODULATION
AB Everyday function demands efficient and flexible decision-making that allows for habitual and goal-directed action control. An inability to shift has been implicated in disorders with impaired decision-making, including obsessive-compulsive disorder and addiction. Despite this, our understanding of the specific molecular mechanisms and circuitry involved in shifting action control remains limited. Here we identify an endogenous molecular mechanism in a specific cortical-striatal pathway that mediates the transition between goal-directed and habitual action strategies. Deletion of cannabinoid type 1 (CB1) receptors from cortical projections originating in the orbital frontal cortex (OFC) prevents mice from shifting from goal-directed to habitual instrumental lever pressing. Activity of OFC neurons projecting to dorsal striatum (OFC-DS) and, specifically, activity of OFC-DS terminals is necessary for goal-directed action control. Lastly, CB1 deletion from OFC-DS neurons prevents the shift from goal-directed to habitual action control. These data suggest that the emergence of habits depends on endocannabinoid-mediated attenuation of a competing circuit controlling goal-directed behaviors.
C1 [Gremel, Christina M.; Chancey, Jessica H.; Atwood, Brady K.; Luo, Guoxiang; Lovinger, David M.] NIAAA, Lab Integrat Neurosci, NIH, Bethesda, MD 20892 USA.
[Gremel, Christina M.] Univ Calif San Diego, Dept Psychol, Neurosci Grad Program, La Jolla, CA 92093 USA.
[Neve, Rachael] MIT, Dept Brain & Cognit Sci, E25-618, Cambridge, MA 02139 USA.
[Ramakrishnan, Charu; Deisseroth, Karl] Stanford Univ, Dept Bioengn, Stanford, CA 94305 USA.
[Costa, Rui M.] Champalimaud Inst Unknown, Champalimaud Neurosci Programme, P-1400038 Lisbon, Portugal.
RP Lovinger, DM (reprint author), NIAAA, Lab Integrat Neurosci, NIH, Bethesda, MD 20892 USA.; Costa, RM (reprint author), Champalimaud Inst Unknown, Champalimaud Neurosci Programme, P-1400038 Lisbon, Portugal.
EM lovindav@mail.nih.gov; rui.costa@neuro.fchampalimaud.org
FU NIAAA Division of Intramural Clinical and Biological Research, ERA-NET;
European Research Council [COG 617142]; HHMI [IEC 55007415]; Pathway to
Independence Award [R00 AA021780]; NARSAD Young Investigator Grant from
the Brain & Behavior Research Foundation
FX We thank Matthew Pava for assistance in the electrophysiological
experiments and Emily Baltz for assistance with intracranial surgeries.
We thank Drs. Beat Lutz and Giovanni Marsicano for providing the
Cnr1loxP/loxP mice. The DREADD virus was provided by the Gene
Therapy and Vector Core at the University of North Carolina. This
research was supported by the NIAAA Division of Intramural Clinical and
Biological Research, ERA-NET; European Research Council (COG 617142) and
HHMI (IEC 55007415) grants to R.M.C.; and Pathway to Independence Award
R00 AA021780 and a NARSAD Young Investigator Grant from the Brain &
Behavior Research Foundation to C.M.G.
NR 56
TC 4
Z9 4
U1 5
U2 8
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0896-6273
EI 1097-4199
J9 NEURON
JI Neuron
PD JUN 15
PY 2016
VL 90
IS 6
BP 1312
EP 1324
DI 10.1016/j.neuron.2016.04.043
PG 13
WC Neurosciences
SC Neurosciences & Neurology
GA DP5HT
UT WOS:000378527600018
PM 27238866
ER
PT J
AU Grimaldi, P
Saleem, KS
Tsao, D
AF Grimaldi, Piercesare
Saleem, Kadharbatcha S.
Tsao, Doris
TI Anatomical Connections of the Functionally Defined "Face Patches'' in
the Macaque Monkey
SO NEURON
LA English
DT Article
ID INFERIOR TEMPORAL CORTEX; PRIMATE CEREBRAL-CORTEX; INFEROTEMPORAL AREA
TE; CORTICAL CONNECTIONS; PREFRONTAL CORTEX; PROCESSING AREAS; LOBE;
NEURONS; REPRESENTATIONS; ORGANIZATION
AB The neural circuits underlying face recognition provide a model for understanding visual object representation, social cognition, and hierarchical information processing. A fundamental piece of information lacking to date is the detailed anatomical connections of the face patches. Here, we injected retrograde tracers into four different face patches (PL, ML, AL, AM) to characterize their anatomical connectivity. We found that the patches are strongly and specifically connected to each other, and individual patches receive inputs from extrastriate cortex, the medial temporal lobe, and three subcortical structures (the pulvinar, claustrum, and amygdala). Inputs from prefrontal cortex were surprisingly weak. Patches were densely interconnected to one another in both feedforward and feedback directions, inconsistent with a serial hierarchy. These results provide the first direct anatomical evidence that the face patches constitute a highly specialized system and suggest that subcortical regions may play a vital role in routing face-related information to subsequent processing stages.
C1 [Grimaldi, Piercesare; Tsao, Doris] CALTECH, Howard Hughes Med Inst, Div Biol & Biol Engn, Pasadena, CA 91125 USA.
[Saleem, Kadharbatcha S.] NIMH, Neuropsychol Lab, Bldg 9, Bethesda, MD 20892 USA.
[Saleem, Kadharbatcha S.] NIMH, NIH, Bethesda, MD 20892 USA.
[Grimaldi, Piercesare] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Fuster Lab Cognit Neurosci, Los Angeles, CA 90095 USA.
RP Grimaldi, P; Tsao, D (reprint author), CALTECH, Howard Hughes Med Inst, Div Biol & Biol Engn, Pasadena, CA 91125 USA.; Grimaldi, P (reprint author), Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Fuster Lab Cognit Neurosci, Los Angeles, CA 90095 USA.
EM pcgrimaldi@gmail.com; dortsao@caltech.edu
FU Howard Hughes Medical Institute; NIH [1R01EY019702, P50 MH942581A]
FX We thank members of the Tsao lab and the three anonymous reviewers for
comments on the manuscript; N. Schweers for technical assistance; and S.
Ohayon, P. Bao, and S. Moeller for assistance with data analysis. The
work was supported by the Howard Hughes Medical Institute and by the NIH
(1R01EY019702, P50 MH942581A).
NR 64
TC 4
Z9 4
U1 4
U2 5
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0896-6273
EI 1097-4199
J9 NEURON
JI Neuron
PD JUN 15
PY 2016
VL 90
IS 6
BP 1325
EP 1342
DI 10.1016/j.neuron.2016.05.009
PG 18
WC Neurosciences
SC Neurosciences & Neurology
GA DP5HT
UT WOS:000378527600019
PM 27263973
ER
PT J
AU Walter, KS
Pepin, KM
Webb, CT
Gaff, HD
Krause, PJ
Pitzer, VE
Diuk-Wasser, MA
AF Walter, Katharine S.
Pepin, Kim M.
Webb, Colleen T.
Gaff, Holly D.
Krause, Peter J.
Pitzer, Virginia E.
Diuk-Wasser, Maria A.
TI Invasion of two tick-borne diseases across New England: harnessing human
surveillance data to capture underlying ecological invasion processes
SO PROCEEDINGS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES
LA English
DT Article
DE invasion; Lyme disease; babesiosis; tick-borne disease; occupancy model
ID VECTOR IXODES-SCAPULARIS; EASTERN UNITED-STATES; HUMAN LYME-DISEASE;
BORRELIA-BURGDORFERI; HUMAN BABESIOSIS; RANGE EXPANSION; METAPOPULATION
DYNAMICS; INFECTIOUS-DISEASE; NANTUCKET-ISLAND; DAMMINI
AB Modelling the spatial spread of vector-borne zoonotic pathogens maintained in enzootic transmission cycles remains a major challenge. The best available spatio-temporal data on pathogen spread often take the form of human disease surveillance data. By applying a classic ecological approach-occupancy modelling-to an epidemiological question of disease spread, we used surveillance data to examine the latent ecological invasion of tick-borne pathogens. Over the last half-century, previously undescribed tick-borne pathogens including the agents of Lyme disease and human babesiosis have rapidly spread across the northeast United States. Despite their epidemiological importance, the mechanisms of tick-borne pathogen invasion and drivers underlying the distinct invasion trajectories of the co-vectored pathogens remain unresolved. Our approach allowed us to estimate the unobserved ecological processes underlying pathogen spread while accounting for imperfect detection of human cases. Our model predicts that tick-borne diseases spread in a diffusion-like manner with occasional long-distance dispersal and that babesiosis spread exhibits strong dependence on Lyme disease.
C1 [Walter, Katharine S.; Krause, Peter J.; Pitzer, Virginia E.; Diuk-Wasser, Maria A.] Yale Univ, Sch Publ Hlth, Dept Epidemiol Microbial Dis, 60 Coll St, New Haven, CT 06520 USA.
[Pepin, Kim M.] US Anim & Plant Hlth Inspect Serv, USDA, Natl Wildlife Res Ctr, 4101 LaPorte Ave, Ft Collins, CO 80521 USA.
[Pepin, Kim M.; Webb, Colleen T.; Pitzer, Virginia E.] NIH, Fogarty Int Ctr, Bldg 10, Bethesda, MD 20892 USA.
[Webb, Colleen T.] Colorado State Univ, Dept Biol, Ft Collins, CO 80523 USA.
[Gaff, Holly D.] Old Dominion Univ, Dept Biol Sci, 302a Mills Godwin Bldg, Norfolk, VA 23529 USA.
[Diuk-Wasser, Maria A.] Columbia Univ, Dept Ecol Evolut & Environm Biol, 1200 Amsterdam Ave, New York, NY 10027 USA.
RP Walter, KS (reprint author), Yale Univ, Sch Publ Hlth, Dept Epidemiol Microbial Dis, 60 Coll St, New Haven, CT 06520 USA.
EM katharine.walter@yale.edu
OI Pitzer, Virginia/0000-0003-1015-2289
FU NIH pre-doctoral training grant [5T32AI007404-23]; NIH Ruth L.
Kirschstein National Research Service Award [F31 AI118233-01A1];
Research and Policy in Disease Dynamics (RAPIDD) programme, Fogarty
International Center, NIH; Department of Homeland Security;
USDA-APHIS-WS; RAPIDD; Gordon and Laura Gund Foundation; National
Institutes of Health, Ecology and Evolution of Infectious Disease
Programme [R01 GM105246]
FX K.S.W. was supported by the NIH pre-doctoral training grant
5T32AI007404-23 and the NIH Ruth L. Kirschstein National Research
Service Award F31 AI118233-01A1. K.M.P. was partly supported by the
Research and Policy in Disease Dynamics (RAPIDD) programme, Fogarty
International Center, NIH and Department of Homeland Security and partly
by USDA-APHIS-WS. C.T.W. and V.E.P. were funded by RAPIDD. P.J.K. was
supported by the Gordon and Laura Gund Foundation. M.D.W. was supported
by the National Institutes of Health, Ecology and Evolution of
Infectious Disease Programme (R01 GM105246).
NR 62
TC 0
Z9 0
U1 10
U2 21
PU ROYAL SOC
PI LONDON
PA 6-9 CARLTON HOUSE TERRACE, LONDON SW1Y 5AG, ENGLAND
SN 0962-8452
EI 1471-2954
J9 P ROY SOC B-BIOL SCI
JI Proc. R. Soc. B-Biol. Sci.
PD JUN 15
PY 2016
VL 283
IS 1832
AR 20160834
DI 10.1098/rspb.2016.0834
PG 10
WC Biology; Ecology; Evolutionary Biology
SC Life Sciences & Biomedicine - Other Topics; Environmental Sciences &
Ecology; Evolutionary Biology
GA DP2KZ
UT WOS:000378318700023
ER
PT J
AU Kon, AA
Davidson, JE
Morrison, W
Danis, M
White, DB
AF Kon, Alexander A.
Davidson, Judy E.
Morrison, Wynne
Danis, Marion
White, Douglas B.
TI Shared Decision-Making in Intensive Care Units Executive Summary of the
American College of Critical Care Medicine and American Thoracic Society
Policy Statement
SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
LA English
DT Editorial Material
ID INTERNATIONAL CONSENSUS CONFERENCE; INFORMED NON-DISSENT; OF-LIFE CARE;
APRIL 2003; ICU; CHALLENGES; DEPRESSION; BRUSSELS; BELGIUM; SUPPORT
C1 [Kon, Alexander A.] Naval Med Ctr San Diego, San Diego, CA USA.
[Kon, Alexander A.] Univ Calif San Diego, San Diego, CA 92103 USA.
[Davidson, Judy E.] Univ Calif Hlth Syst, San Diego, CA USA.
[Morrison, Wynne] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA.
[Danis, Marion] NIH, Bldg 10, Bethesda, MD 20892 USA.
[White, Douglas B.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA.
RP Kon, AA (reprint author), Naval Med Ctr San Diego, San Diego, CA USA.; Kon, AA (reprint author), Univ Calif San Diego, San Diego, CA 92103 USA.
NR 24
TC 2
Z9 2
U1 0
U2 2
PU AMER THORACIC SOC
PI NEW YORK
PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA
SN 1073-449X
EI 1535-4970
J9 AM J RESP CRIT CARE
JI Am. J. Respir. Crit. Care Med.
PD JUN 15
PY 2016
VL 193
IS 12
BP 1334
EP 1336
PG 3
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA DO8FF
UT WOS:000378017300008
PM 27097019
ER
PT J
AU Jang, H
Muratcioglu, S
Gursoy, A
Keskin, O
Nussinov, R
AF Jang, Hyunbum
Muratcioglu, Serena
Gursoy, Attila
Keskin, Ozlem
Nussinov, Ruth
TI Membrane-associated Ras dimers are isoform-specific: K-Ras dimers differ
from H-Ras dimers
SO BIOCHEMICAL JOURNAL
LA English
DT Article
DE HVR; K-Ras4B; nanoclusters; Raf activation; Raf dimerization; Ras
interfaces; plasma membrane; signalling
ID CONTINUUM ELECTROSTATICS CALCULATIONS; FREE-ENERGY DECOMPOSITION;
AMYLOID ION CHANNELS; SMALL GTPASE K-RAS4B; MOLECULAR-DYNAMICS;
PLASMA-MEMBRANE; HYPERVARIABLE REGION; PROTEIN INTERACTIONS; FORMS
DIMERS; ATOMIC RADII
AB Are the dimer structures of active Ras isoforms similar? This question is significant since Ras can activate its effectors as a monomer; however, as a dimer, it promotes Raf's activation and MAPK (mitogen-activated protein kinase) cell signalling. In the present study, we model possible catalytic domain dimer interfaces of membrane-anchored GTP-bound K-Ras4B and H-Ras, and compare their conformations. The active helical dimers formed by the allosteric lobe are isoform-specific: K-Ras4B-GTP favours the alpha 3 and alpha 4 interface; H-Ras-GTP favours alpha 4 and alpha 5. Both isoforms also populate a stable beta-sheet dimer interface formed by the effector lobe; a less stable beta-sandwich interface is sustained by salt bridges of the beta-sheet side chains. Raf's high-affinity beta-sheet interaction is promoted by the active helical interface. Collectively, Ras isoforms' dimer conformations are not uniform; instead, the isoform-specific dimers reflect the favoured interactions of the HVRs (hypervariable regions) with cell membrane microdomains, biasing the effector-binding site orientations, thus isoform binding selectivity.
C1 [Jang, Hyunbum; Nussinov, Ruth] NCI, Canc & Inflammat Program, Basic Sci Program, Leidos Biomed Res Inc,Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
[Muratcioglu, Serena; Keskin, Ozlem] Koc Univ, Dept Chem & Biol Engn, Istanbul, Turkey.
[Gursoy, Attila] Koc Univ, Dept Comp Engn, Istanbul, Turkey.
[Nussinov, Ruth] Tel Aviv Univ, Sackler Sch Med, Dept Human Mol Genet & Biochem, IL-69978 Tel Aviv, Israel.
RP Nussinov, R (reprint author), NCI, Canc & Inflammat Program, Basic Sci Program, Leidos Biomed Res Inc,Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.; Nussinov, R (reprint author), Tel Aviv Univ, Sackler Sch Med, Dept Human Mol Genet & Biochem, IL-69978 Tel Aviv, Israel.
EM NussinoR@helix.nih.gov
RI Gursoy, Attila/E-9565-2015
OI Gursoy, Attila/0000-0002-2297-2113
FU Federal funds from the Frederick National Laboratory for Cancer
Research, National Institutes of Health [HHSN261200800001E]; Intramural
Research Program of the National Institutes of Health, Frederick
National Laboratory, Center for Cancer Research; Turkiye Bilimsel ve
Teknolojik Arastirma Kurumu (TUBITAK) (Scientific and Technological
Research Council of Turkey) [114M196]
FX This project has been funded in whole or in part with Federal funds from
the Frederick National Laboratory for Cancer Research, National
Institutes of Health [grant number HHSN261200800001E]. This research was
supported in part by the Intramural Research Program of the National
Institutes of Health, Frederick National Laboratory, Center for Cancer
Research. The content of this publication does not necessarily reflect
the views or policies of the Department of Health and Human Services,
nor does mention of trade names, commercial products or organizations
imply endorsement by the U.S. Government. This work has been partially
supported by the Turkiye Bilimsel ve Teknolojik Arastirma Kurumu
(TUBITAK) (Scientific and Technological Research Council of Turkey)
[grant number 114M196].
NR 69
TC 5
Z9 5
U1 5
U2 12
PU PORTLAND PRESS LTD
PI LONDON
PA CHARLES DARWIN HOUSE, 12 ROGER STREET, LONDON WC1N 2JU, ENGLAND
SN 0264-6021
EI 1470-8728
J9 BIOCHEM J
JI Biochem. J.
PD JUN 15
PY 2016
VL 473
BP 1719
EP 1732
DI 10.1042/BCJ20160031
PN 12
PG 14
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA DO7WC
UT WOS:000377992700006
PM 27057007
ER
PT J
AU Carlson, KSB
Nguyen, L
Schwartz, K
Lawrence, DA
Schwartz, BS
AF Carlson, Karen-Sue B.
Lan Nguyen
Schwartz, Kat
Lawrence, Daniel A.
Schwartz, Bradford S.
TI Neuroserpin Differentiates Between Forms of Tissue Type Plasminogen
Activator via pH Dependent Deacylation
SO FRONTIERS IN CELLULAR NEUROSCIENCE
LA English
DT Article
DE neuroserpin; tissue plasminogen activator; serpin; serine protease;
decacylation
ID SERPIN-PROTEINASE COMPLEX; SERINE-PROTEASE INHIBITOR; RECEPTOR-RELATED
PROTEIN; RAT HIPPOCAMPAL-NEURONS; LONG-TERM POTENTIATION; D-ASPARTATE
RECEPTORS; REACTIVE CENTER LOOP; BLOOD-BRAIN-BARRIER; SINGLE-CHAIN FORM;
FOREBRAIN ISCHEMIA
AB Tissue-type plasminogen activator (t-PA), initially characterized for its critical role in fibrinolysis, also has key functions in both physiologic and pathologic processes in the CNS. Neuroserpin (NSF) is a t-PA specific serine protease inhibitor (serpin) found almost exclusively in the CNS that regulates t-PA's proteolytic activity and protects against t-PA mediated seizure propagation and blood brain barrier disruption. This report demonstrates that NSP inhibition of t-PA varies profoundly as a function of pH within the biologically relevant pH range for the CNS, and reflects the stability, rather than the formation of NSP: t-PA acyl-enzyme complexes. Moreover, NSP differentiates between the zymogen-like single chain form (single chain t-PA, sct-PA) and the mature protease form (two chain t-PA, tct-PA) of t-PA, demonstrating different pH profiles for protease inhibition, different pH ranges over which catalytic deacylation occurs, and different pH dependent profiles of deacylation rates for each form of t-PA. NSP's pH dependent inhibition of t-PA is not accounted for by differential acylation, and is specific for the NSP-t-PA serpin-protease pair. These results demonstrate a novel mechanism for the differential regulation of the two forms of t-PA in the CNS, and suggest a potential specific regulatory role for CNS pH in controlling t-PA proteolytic activity.
C1 [Carlson, Karen-Sue B.; Schwartz, Bradford S.] Univ Wisconsin, Dept Biomol Chem, Madison, WI USA.
[Carlson, Karen-Sue B.] Univ Wisconsin, Med Scientist Training Program, Madison, WI USA.
[Lan Nguyen; Schwartz, Kat; Schwartz, Bradford S.] Univ Illinois, Dept Biochem, Urbana, IL 61801 USA.
[Lan Nguyen; Schwartz, Kat; Schwartz, Bradford S.] Univ Illinois, Dept Med, Urbana, IL 61801 USA.
[Lawrence, Daniel A.] Univ Michigan, Dept Med, Ann Arbor, MI 48109 USA.
[Lawrence, Daniel A.] Univ Michigan, Dept Mol & Integrat Physiol, Ann Arbor, MI 48109 USA.
[Carlson, Karen-Sue B.] Med Coll Wisconsin, Dept Internal Med, Milwaukee, WI 53226 USA.
[Lan Nguyen] Indiana Univ, Dept Med & Pediat, Indianapolis, IN 46204 USA.
[Schwartz, Kat] NIH, Natl Ctr Advancing Translat Sci, Bldg 10, Bethesda, MD 20892 USA.
RP Schwartz, BS (reprint author), Univ Wisconsin, Dept Biomol Chem, Madison, WI USA.; Schwartz, BS (reprint author), Univ Illinois, Dept Biochem, Urbana, IL 61801 USA.; Schwartz, BS (reprint author), Univ Illinois, Dept Med, Urbana, IL 61801 USA.
EM bschwartz@morgridge.org
FU National Institutes of Health [PHS HL-43506, PHS HL055374, NS079639]
FX This publication was made possible by National Institutes of Health
grants to BS [PHS HL-43506; PHS HL055374] and to DL [PHS HL055374 and
NS079639]; and also from the Carle Foundation, Urbana, IL to BS.
NR 78
TC 1
Z9 1
U1 1
U2 3
PU FRONTIERS MEDIA SA
PI LAUSANNE
PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015,
SWITZERLAND
SN 1662-5102
J9 FRONT CELL NEUROSCI
JI Front. Cell. Neurosci.
PD JUN 15
PY 2016
VL 10
AR 154
DI 10.3389/fncel/2016.00154
PG 11
WC Neurosciences
SC Neurosciences & Neurology
GA DO7LH
UT WOS:000377963600001
PM 27378851
ER
PT J
AU Vacchio, MS
Bosselut, R
AF Vacchio, Melanie S.
Bosselut, Remy
TI What Happens in the Thymus Does Not Stay in the Thymus: How T Cells
Recycle the CD4(+)-CD8(+) Lineage Commitment Transcriptional Circuitry
To Control Their Function
SO JOURNAL OF IMMUNOLOGY
LA English
DT Review
ID INNATE LYMPHOID-CELLS; HELPER TYPE-1 CELLS; FINGER PROTEIN MAZR; CD4
EXPRESSION; NEGATIVE SELECTION; POSITIVE SELECTION; GENE-EXPRESSION;
RUNX PROTEINS; THYMOCYTE DIFFERENTIATION; IMMUNODEFICIENCY-VIRUS
AB MHC-restricted CD4(+) and CD8(+) T cells are at the core of most adaptive immune responses. Although these cells carry distinct functions, they arise from a common precursor during thymic differentiation, in a developmental sequence that matches CD4 and CD8 expression and functional potential with MHC restriction. Although the transcriptional control of CD4(+)-CD8(+) lineage choice in the thymus is now better understood, less was known about what maintains the CD4(+) and CD8(+) lineage integrity of mature T cells. In this review, we discuss the mechanisms that establish in the thymus, and maintain in postthymic cells, the separation of these lineages. We focus on recent studies that address the mechanisms of epigenetic control of Cd4 expression and emphasize how maintaining a transcriptional circuitry nucleated around Thpok and Runx proteins, the key architects of CD4(+)-CD8(+) lineage commitment in the thymus, is critical for CD4(+) T cell helper functions.
C1 [Vacchio, Melanie S.; Bosselut, Remy] NCI, Lab Immune Cell Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Bosselut, R (reprint author), NCI, Lab Immune Cell Biol, NIH, Bldg 37,Room 3032,37 Convent Dr, Bethesda, MD 20892 USA.
EM remy@helix.nih.gov
FU Intramural Research Program of the National Cancer Institute, Center for
Cancer Research
FX We thank P. Love and T. Ciucci for useful discussions and J.D. Ashwell,
P. Love, and T. Ciucci for reading the manuscript. We apologize to
colleagues whose work could not be discussed because of space
limitations. Research work in the authors' laboratory is supported by
the Intramural Research Program of the National Cancer Institute, Center
for Cancer Research.
NR 110
TC 2
Z9 2
U1 5
U2 7
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
EI 1550-6606
J9 J IMMUNOL
JI J. Immunol.
PD JUN 15
PY 2016
VL 196
IS 12
BP 4848
EP 4856
DI 10.4049/jimmunol.1600415
PG 9
WC Immunology
SC Immunology
GA DO7BP
UT WOS:000377937500002
PM 27260768
ER
PT J
AU Martin-Avila, A
Medina-Tamayo, J
Ibarra-Sanchez, A
Vazquez-Victorio, G
Castillo-Arellano, JI
Hernandez-Mondragon, AC
Rivera, J
Madera-Salcedo, IK
Blank, U
Macias-Silva, M
Gonzalez-Espinosa, C
AF Martin-Avila, Alejandro
Medina-Tamayo, Jaciel
Ibarra-Sanchez, Alfredo
Vazquez-Victorio, Genaro
Ivan Castillo-Arellano, Jorge
Cristal Hernandez-Mondragon, Alma
Rivera, Juan
Madera-Salcedo, Iris K.
Blank, Ulrich
Macias-Silva, Marina
Gonzalez-Espinosa, Claudia
TI Protein Tyrosine Kinase Fyn Regulates TLR4-Elicited Responses on Mast
Cells Controlling the Function of a PP2A-PKC alpha/beta Signaling Node
Leading to TNF Secretion
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID NF-KAPPA-B; PHOSPHATASE 2A; ENDOTOXIN TOLERANCE; CYTOKINE PRODUCTION;
GENE-EXPRESSION; INNATE IMMUNITY; LYN KINASE; ACTIVATION; DEGRANULATION;
PATHWAYS
AB Mast cells produce proinflammatory cytokines in response to TLR4 ligands, but the signaling pathways involved are not fully described. In this study, the participation of the Src family kinase Fyn in the production of TNF after stimulation with LPS was evaluated using bone marrow-derived mast cells from wild-type and Fyn-deficient mice. Fyn(-/-) cells showed higher LPS-induced secretion of preformed and de novo-synthesized TNF. In both cell types, TNF colocalized with vesicle-associated membrane protein (VAMP) 3-positive compartments. Addition of LPS provoked coalescence of VAMP3 and its interaction with synaptosomal-associated protein 23; those events were increased in the absence of Fyn. Higher TNF mRNA levels were also observed in Fyn-deficient cells as a result of increased transcription and greater mRNA stability after LPS treatment. Fyn(-/-) cells also showed higher LPS-induced activation of TAK-1 and ERK1/2, whereas I kappa B kinase and I kappa B were phosphorylated, even in basal conditions. Increased responsiveness in Fyn(-/-) cells was associated with a lower activity of protein phosphatase 2A (PP2A) and augmented activity of protein kinase C (PKC)alpha/beta, which was dissociated from PP2A and increased its association with the adapter protein neuroblast differentiation-associated protein (AHNAK, desmoyokin). LPS-induced PKC alpha/beta activity was associated with VAMP3 coalescence in WT and Fyn-deficient cells. Reconstitution of MC-deficient Wsh mice with Fyn(-/-) MCs produced greater LPS-dependent production of TNF in the peritoneal cavity. Our data show that Fyn kinase is activated after TLR4 triggering and exerts an important negative control on LPS-dependent TNF production in MCs controlling the inactivation of PP2Ac and activation of PKC alpha/beta necessary for the secretion of TNF by VAMP3(+) carriers.
C1 [Martin-Avila, Alejandro; Medina-Tamayo, Jaciel; Ibarra-Sanchez, Alfredo; Ivan Castillo-Arellano, Jorge; Cristal Hernandez-Mondragon, Alma; Gonzalez-Espinosa, Claudia] Inst Politecn Nacl, Ctr Invest & Estudios Avanzados, Dept Farmacobiol, Calzada Tenorios 235, Mexico City 14330, DF, Mexico.
[Vazquez-Victorio, Genaro; Macias-Silva, Marina] Univ Nacl Autonoma Mexico, Dept Biol Celular & Desarrollo, Inst Fisiol Celular, Ciudad Univ, Mexico City 04510, DF, Mexico.
[Rivera, Juan] NIAMSD, NIH, Bethesda, MD 20892 USA.
[Madera-Salcedo, Iris K.; Blank, Ulrich] Univ Paris Diderot, INSERM, Fac Med, UMRS1149, Site 10, F-75018 Paris, France.
RP Gonzalez-Espinosa, C (reprint author), Inst Politecn Nacl, Ctr Invest & Estudios Avanzados, Dept Farmacobiol, Calzada Tenorios 235, Mexico City 14330, DF, Mexico.
EM cgonzal@cinvestav.mx
FU Consejo Nacional de Ciencia y Tecnologia Mexico (Conacyt)
[Conacyt-ANR188565]; Agence Nationale de la Recherche France
[ANR-12-ISV3-0006-01]; Conacyt [404373]
FX This work was supported by an international collaboration grant between
Consejo Nacional de Ciencia y Tecnologia Mexico (Conacyt)
(Conacyt-ANR188565) and Agence Nationale de la Recherche France
(ANR-12-ISV3-0006-01) and scholarship 404373 from Conacyt (to
J.I.C.-A.).
NR 75
TC 1
Z9 1
U1 1
U2 1
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
EI 1550-6606
J9 J IMMUNOL
JI J. Immunol.
PD JUN 15
PY 2016
VL 196
IS 12
BP 5075
EP 5088
DI 10.4049/jimmunol.1501823
PG 14
WC Immunology
SC Immunology
GA DO7BP
UT WOS:000377937500025
PM 27183589
ER
PT J
AU Dodd, LE
Proschan, MA
Neuhaus, J
Koopmeiners, JS
Neaton, J
Beigel, JD
Barrett, K
Lane, HC
Davey, RT
AF Dodd, Lori E.
Proschan, Michael A.
Neuhaus, Jacqueline
Koopmeiners, Joseph S.
Neaton, James
Beigel, John D.
Barrett, Kevin
Lane, Henry Clifford
Davey, Richard T., Jr.
TI Design of a Randomized Controlled Trial for Ebola Virus Disease Medical
Countermeasures: PREVAIL II, the Ebola MCM Study
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
DE emerging infectious diseases; Ebola virus disease; clinical trials;
adaptive design; Bayesian design
ID CLINICAL-TRIALS; OUTCOMES; CANCER
AB Background. Unique challenges posed by emerging infectious diseases often expose inadequacies in the conventional phased investigational therapeutic development paradigm. The recent Ebola outbreak in West Africa presents a critical case-study highlighting barriers to faster development. During the outbreak, clinical trials were implemented with unprecedented speed. Yet, in most cases, this fast-tracked approach proved too slow for the rapidly evolving epidemic. Controversy abounded as to the most appropriate study designs to yield safety and efficacy data, potentially causing delays in pivotal studies. Preparation for research during future outbreaks may require acceptance of a paradigm that circumvents, accelerates, or reorders traditional phases, without losing sight of the traditional benchmarks by which drug candidates must be assessed for activity, safety and efficacy.
Methods. We present the design of an adaptive, parent protocol, ongoing in West Africa until January 2016. The exigent circumstances of the outbreak and limited prior clinical experience with experimental treatments, led to more direct bridging from preclinical studies to human trials than the conventional paradigm would typically have sanctioned, and required considerable design flexibility.
Results. Preliminary evaluation of the "barely Bayesian" design was provided through computer simulation studies. The understanding and public discussion of the study design will help its future implementation.
C1 [Dodd, Lori E.; Proschan, Michael A.; Barrett, Kevin; Lane, Henry Clifford; Davey, Richard T., Jr.] NIAID, 6700 B Rockledge,5601 Fishers Lane,MSC 9820, Bethesda, MD 20892 USA.
[Beigel, John D.] Frederick Natl Lab Canc Res, Leidos Biomed Res, Frederick, MD USA.
[Neuhaus, Jacqueline; Koopmeiners, Joseph S.; Neaton, James] Univ Minnesota, Sch Publ Hlth, Div Biostat, Minneapolis, MN 55455 USA.
RP Dodd, LE (reprint author), NIAID, 6700 B Rockledge,5601 Fishers Lane,MSC 9820, Bethesda, MD 20892 USA.
EM doddl@mail.nih.gov
FU Division of Clinical Research, National Institute of Allergy and
Infectious Diseases; National Cancer Institute, National Institutes of
Health [HHSN261200800001E]
FX This work was partially funded by the Division of Clinical Research,
National Institute of Allergy and Infectious Diseases. This project has
been funded in part with federal funds from the National Cancer
Institute, National Institutes of Health (contract HHSN261200800001E).
NR 14
TC 8
Z9 8
U1 0
U2 6
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0022-1899
EI 1537-6613
J9 J INFECT DIS
JI J. Infect. Dis.
PD JUN 15
PY 2016
VL 213
IS 12
BP 1906
EP 1913
DI 10.1093/infdis/jiw061
PG 8
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA DO0BL
UT WOS:000377444300009
PM 26908739
ER
PT J
AU Clark, CE
Fay, MP
Chico, ME
Sandoval, CA
Vaca, MG
Boyd, A
Cooper, PJ
Nutman, TB
AF Clark, Carolyn E.
Fay, Michael P.
Chico, Martha E.
Sandoval, Carlos A.
Vaca, Maritza G.
Boyd, Alexis
Cooper, Philip J.
Nutman, Thomas B.
TI Maternal Helminth Infection Is Associated With Higher Infant
Immunoglobulin A Titers to Antigen in Orally Administered Vaccines
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
DE maternal; helminth; vaccine; immunization; IgA
ID MYCOBACTERIAL ANTIGENS; GEOHELMINTH INFECTIONS; DEVELOPING-COUNTRIES;
ROTAVIRUS VACCINES; ANTIBODY-RESPONSE; IMMUNE-RESPONSES;
CONTROLLED-TRIAL; CHOLERA VACCINE; BIRTH COHORT; CHILDREN
AB Background. Many studies have documented lower vaccine efficacy among children in low-income countries, compared with their counterparts in high-income countries. This disparity is especially apparent with respect to oral vaccines such as rotavirus and oral polio vaccines. One potential contributing factor is the presence of maternal antenatal helminth infections, which can modulate the infant's developing immune system.
Methods. Using a multiplex immunoassay, we tested plasma immunoglobulin A (IgA) or immunoglobulin G (IgG) levels specific for antigens in 9 routinely administered childhood vaccines among 1639 children aged approximately 13 months enrolled in the ECUAVIDA (Ecuador Life) birth cohort study in Ecuador. We compared vaccine responses in 712 children of mothers who tested positive for helminth infections in the last trimester of pregnancy to responses in 927 children of mothers without helminth infection.
Results. Plasma IgA levels specific for antigens in rotavirus vaccine and oral polio vaccine containing poliovirus serotypes 1 and 3 were all significantly higher in children of helminth-infected mothers, compared with children of uninfected mothers. Plasma IgG levels specific for diphtheria, tetanus, pertussis, measles, rubella, and Haemophilus influenzae type b vaccine antigens were comparable between the 2 groups.
Conclusions. Antenatal maternal helminth infections were not associated with reduced antibody responses to infant vaccines, but rather with modestly increased IgA responses to oral vaccines.
C1 [Clark, Carolyn E.; Boyd, Alexis; Nutman, Thomas B.] NIAID, Parasit Dis Lab, NIH, Bethesda, MD USA.
[Fay, Michael P.] NIAID, Biostat Res Branch, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Chico, Martha E.; Sandoval, Carlos A.; Vaca, Maritza G.; Cooper, Philip J.] Lab Invest FEPIS, Quininde, Ecuador.
[Cooper, Philip J.] Pontificia Univ Catolica Ecuador, Fac Ciencias Exactas & Nat, Ctr Invest Enfermedades Infecciosas & Cron, Quito, Ecuador.
[Cooper, Philip J.] St Georges Univ London, Inst Infect & Immun, London, England.
[Clark, Carolyn E.] Norwegian Inst Publ Hlth, Domain Infect Control & Environm Hlth, Oslo, Norway.
[Boyd, Alexis] Bill & Melinda Gates Fdn, Seattle, WA USA.
RP Nutman, TB (reprint author), NIH, Parasit Dis Lab, Bldg 4,Rm B1-03,4 Ctr Dr, Bethesda, MD 20892 USA.
EM tnutman@niaid.nih.gov
FU Wellcome Trust [088862/Z/09/Z]; Division of Intramural Research,
National Institute of Allergy and Infectious Diseases
FX This work was supported by the Wellcome Trust (grant 088862/Z/09/Z) and
the Division of Intramural Research, National Institute of Allergy and
Infectious Diseases.
NR 32
TC 3
Z9 3
U1 0
U2 4
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0022-1899
EI 1537-6613
J9 J INFECT DIS
JI J. Infect. Dis.
PD JUN 15
PY 2016
VL 213
IS 12
BP 1996
EP 2004
DI 10.1093/infdis/jiw066
PG 9
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA DO0BL
UT WOS:000377444300021
PM 26908751
ER
PT J
AU Wennberg, AMV
Spira, AP
Pettigrew, C
Soldan, A
Zipunnikov, V
Rebok, GW
Roses, AD
Lutz, MW
Miller, MM
Thambisetty, M
Albert, MS
AF Wennberg, Alexandra M. V.
Spira, Adam P.
Pettigrew, Corinne
Soldan, Anja
Zipunnikov, Vadim
Rebok, George W.
Roses, Allen D.
Lutz, Michael W.
Miller, Michael M.
Thambisetty, Madhav
Albert, Marilyn S.
TI Blood glucose levels and cortical thinning in cognitively normal,
middle-aged adults
SO JOURNAL OF THE NEUROLOGICAL SCIENCES
LA English
DT Article
DE Cortical thinning; Alzheimer's disease; APOE; TOMM40; Blood glucose
ID WHITE-MATTER INTEGRITY; SURFACE-BASED ANALYSIS; HUMAN CEREBRAL-CORTEX;
ALZHEIMERS-DISEASE; APOLIPOPROTEIN-E; MITOCHONDRIAL DYSFUNCTION;
HIPPOCAMPAL ATROPHY; INSULIN-RESISTANCE; DIABETES-MELLITUS; COORDINATE
SYSTEM
AB Type II diabetes mellitus (DM) increases risk for cognitive decline and is associated with brain atrophy in older demented and non-demented individuals. We investigated (1) the cross-sectional association between fasting blood glucose level and cortical thickness in a sample of largely middle-aged, cognitively normal adults, and (2) whether these associations were modified by genes associated with both lipid processing and dementia. To explore possible modifications by genetic status, we investigated the interaction between blood glucose levels and the apolipoprotein E (APOE) epsilon 4 allele and the translocase of the outer mitochondrial membrane (TOMM) 40 '523 genotype on cortical thickness. Cortical thickness measures were based on mean thickness in a subset of a priori-selected brain regions hypothesized to be vulnerable to atrophy in Alzheimer's disease (AD) (i.e., 'AD vulnerable regions'). Participants included 233 cognitively normal subjects in the BIOCARD study who had a measure of fasting blood glucose and cortical thickness measures, quantified by magnetic resonance imaging (MRI) scans. After adjustment for age, sex, race, education, depression, and medical conditions, higher blood glucose was associated with thinner parahippocampal gyri (B = -0.002; 95% CI -0.004, -0.0004) and temporal pole (B = -0.002; 95% CI -0.004, -0.0001), as well as reduced average thickness over AD vulnerable regions (B = -0.001; 95% CI -0.002, -0.0001). There was no evidence for greater cortical thinning in c4 carriers of the APOE gene or in APOE epsilon 3/3 individuals carrying the TOMM40 VL/VL genotypes. When individuals with glucose levels in the diabetic range (>= 126 mg/dL), were excluded from the analysis, the associations between glucose levels and cortical thickness were no longer significant. These findings suggest that glucose levels in the diabetic range are associated with reduced cortical thickness in AD vulnerable regions as early as middle age. (C) 2016 Elsevier B.V. All rights reserved.
C1 [Wennberg, Alexandra M. V.; Spira, Adam P.; Rebok, George W.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Mental Hlth, 615 N Wolfe St, Baltimore, MD 21205 USA.
[Spira, Adam P.; Rebok, George W.] Johns Hopkins Sch Med, Dept Psychiat & Behav Sci, 733 N Broadway, Baltimore, MD 21205 USA.
[Spira, Adam P.; Zipunnikov, Vadim; Rebok, George W.] Johns Hopkins Ctr Aging & Hlth, 2024 E Monument St, Baltimore, MD 21205 USA.
[Pettigrew, Corinne; Soldan, Anja; Albert, Marilyn S.] Johns Hopkins Sch Med, Dept Neurol, 733 N Broadway, Baltimore, MD 21205 USA.
[Zipunnikov, Vadim] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Biostat, 615 N Wolfe St, Baltimore, MD 21205 USA.
[Roses, Allen D.; Lutz, Michael W.] Duke Univ, Sch Med, Dept Neurol, 8 Searle Ctr Dr, Durham, NC 27703 USA.
[Miller, Michael M.] Johns Hopkins Univ, Dept Biomed Engn, 3400 N Charles St, Baltimore, MD 21218 USA.
[Thambisetty, Madhav] NIA, Unit Clin & Translat Neurosci, 251 Bayview Blvd, Baltimore, MD 21224 USA.
RP Wennberg, AMV (reprint author), Mayo Clin, Dept Hlth Sci Res, 200 1st St SW, Rochester, MN 55905 USA.
EM wennberg.alexandra@mayo.edu; aspira@jhu.edu; cpettigrew@jhmi.edu;
asoldan1@jhmi.edu; vadim.zipunnikov@gmail.com; grebok1@jhu.edu;
allen.roses@duke.edu; michael.lutz@duke.edu; mim@cis.jhu.edu;
thambisettym@mail.nih.gov; malbert9@jhmi.edu
RI Wennberg, Alexandra/O-9563-2016;
OI Wennberg, Alexandra/0000-0003-4906-1165; Lutz,
Michael/0000-0001-8809-5574
FU National Institute on Aging; Johns Hopkins University; William and Ella
Owens Medical Research Foundation; National Institutes of Health
[U19-AG03365, P50-AG005146, T32-AG027668]
FX Drs. Wennberg, Pettigrew, Soldan, Zipunnikov, Rebok, Lutz, Miller,
Thambisetty, and Albert report no conflicts of interest. Dr. Spira has
received grants from the National Institute on Aging, Johns Hopkins
University, and the William and Ella Owens Medical Research Foundation.
Dr. Roses is the Jefferson-Pilot Professor of Neurosciences and
Neurology at Duke University. Dr. Roses is the CEO and sole shareholder
of Zinfandel Pharmaceuticals, Inc. (a NC S-Corp). Zinfandel is an
alliance with Takeda Pharmaceuticals to manage the TOMMORROW study.;
This study was supported in part by grants from the National Institutes
of Health (U19-AG03365, P50-AG005146, and T32-AG027668). The BIOCARD
Study consists of 7 Cores with the following members: (1) the
Administrative Core (Marilyn Albert, Barbara Rodzon); (2) the Clinical
Core (Ola Seines, Marilyn Albert, Anja Soldan, Rebecca Gottesman, Ned
Sacktor, Guy McKhann, Scott Turner, Leonie Farrington, Maura Grega, Gay
Rudow, Daniel D'Agostino, Scott Rudow); (3) the Imaging Core (Michael
Miller, Susumu Mori, Tilak Ratnanather, Timothy Brown, Hayan Chi,
Anthony Kolasny, Kenichi Oishi, Thomas Reigel, Laurent Younes); (4) the
Biospecimen Core (Abhay Moghekar, Richard O'Brien, Abby Spangler); (5)
the Informatics Core (Roberta Scherer, David Shade, Ann Ervin, Jennifer
Jones, Matt Toepfner, Lauren Parlett, April Patterson, Aisha Mohammed);
(6) the Biostatistics Core (Mei-Cheng Wang, Qing Cai, Daisy Lu); and (7)
the Neuropathology Core (Juan Troncoso, Barbara Crain, Olga Pletnikova,
Gay Rudow, and Karen Fisher). The authors are grateful to the members of
the BIOCARD Scientific Advisory Board who provide continued oversight
and guidance regarding the conduct of the study including: Drs John
Cemansky, David Holtzman, David Knopman, Walter Kukull, and John
McArdle, and Drs Neil Buckholtz, John Hsiao, Laurie Ryan, and Jovier
Evans, who provide oversight on behalf of the National Institute on
Aging and the National Institute of Mental Health (NIMH), respectively.
The authors thank the members of the BIOCARD Resource Allocation
Committee who provide ongoing guidance regarding the use of the
biospecimens collected as part of the study, including: Drs Constantine
Lyketsos, Carlos Pardo, Gerard Schellenberg, Leslie Shaw, Madhav
Thambisetty, and John Trojanowski.
NR 56
TC 1
Z9 1
U1 1
U2 8
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0022-510X
EI 1878-5883
J9 J NEUROL SCI
JI J. Neurol. Sci.
PD JUN 15
PY 2016
VL 365
BP 89
EP 95
DI 10.1016/j.jns.2016.04.017
PG 7
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA DN8FC
UT WOS:000377313600020
PM 27206882
ER
PT J
AU Climaco-Arvizu, S
Dominguez-Acosta, O
Cabanas-Cortes, MA
Rodriguez-Sosa, M
Gonzalez, FJ
Vega, L
Elizondo, G
AF Climaco-Arvizu, Samantha
Dominguez-Acosta, Omar
Asuncion Cabanas-Cortes, Maria
Rodriguez-Sosa, Miriam
Gonzalez, Frank J.
Vega, Libia
Elizondo, Guillermo
TI Aryl hydrocarbon receptor influences nitric oxide and arginine
production and alters M1/M2 macrophage polarization
SO LIFE SCIENCES
LA English
DT Article
DE Arginase; Aryl hydrocarbon receptor; Leishmaniasis; Macrophage; Nitric
oxide
ID AHR-NULL MICE; SYNTHASE EXPRESSION; INFECTION; ARGINASE; INFLAMMATION;
LEISHMANIA; METABOLISM; TOXICITY
AB Aims: The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that mediates the toxicity of environmental pollutants. It is also implicated in the regulation of the immune system. Ahr-null macrophages overproduce several proinflammatory cytokines following LPS-mediated stimulation, suggesting that AHR affects the balance between the inflammatory M1 and anti-inflammatory M2 phenotypes. Therefore, the present study aimed to examine whether the loss of AHR modifies macrophage polarization.
Materials and methods: Peritoneal macrophages fromwild-type and Ahr-null mice were differentiated into M1 or M2 phenotype by treatment with LPS/IFN gamma or IL-4, and several M1 and M2 markers were determined by qPCR and ELISA assays. Macrophage phagocytic capacity was determined through phagocytosis of yeast and Leishmania major infection assays. Nitric oxide (NO) and urea production, and arginase activity were also determined.
Key findings: When macrophages were polarized to the M1 phenotype, Ahr-null cells presented a mixed response; higher levels of IL-1 beta, IL-6, IL-12, and TNF alpha were observed after IFN gamma- and LPS-mediated activation. However, Ahr-null cells also exhibited decreased NO production and phagocytic capacity. When macrophage was polarized to the M2 phenotype, Ahr-null cells exhibited lower levels of Fizz1, Ym1, and IL-10. In contrast, arginase activity was increased when compared to wild-type macrophages. In addition, macrophages from Ahrnull mice were more susceptible to L. major infection.
Significance: Disruption of the Ahr gene alters macrophage polarization when compared to WT macrophage. These changes may affect the development and resolution of several diseases such as bacterial or parasitic infections. (C) 2016 Elsevier Inc. All rights reserved.
C1 [Climaco-Arvizu, Samantha; Dominguez-Acosta, Omar; Asuncion Cabanas-Cortes, Maria; Elizondo, Guillermo] CINVESTAV IPN, Dept Biol Celular, Av IPN 2508, Mexico City 07360, DF, Mexico.
[Rodriguez-Sosa, Miriam] UNAM, Fac Estudios Super Iztacala, Unidad Biomed, Tlalnepantla 54090, Estado De Mexic, Mexico.
[Gonzalez, Frank J.] NCI, Lab Metab, NIH, Bethesda, MD 20892 USA.
[Vega, Libia] CINVESTAV IPN, Dept Toxicol, Av IPN 2508, Mexico City 07360, DF, Mexico.
RP Elizondo, G (reprint author), CINVESTAV IPN, Dept Biol Celular, Av IPN 2508, Mexico City 07360, DF, Mexico.
EM gazuela@cinvestav.mx
FU CONACYT [153377]
FX We thank Dr. Leopoldo Flores for his helpful comments. This work was
supported by CONACYT grant number 153377.
NR 31
TC 0
Z9 0
U1 1
U2 5
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0024-3205
EI 1879-0631
J9 LIFE SCI
JI Life Sci.
PD JUN 15
PY 2016
VL 155
BP 76
EP 84
DI 10.1016/j.lfs.2016.05.001
PG 9
WC Medicine, Research & Experimental; Pharmacology & Pharmacy
SC Research & Experimental Medicine; Pharmacology & Pharmacy
GA DO1LW
UT WOS:000377540700011
PM 27153778
ER
PT J
AU Barch, DM
Gotlib, IH
Bilder, RM
Pine, DS
Smoller, JW
Brown, CH
Huggins, W
Hamilton, C
Haim, A
Farber, GK
AF Barch, Deanna M.
Gotlib, Ian H.
Bilder, Robert M.
Pine, Daniel S.
Smoller, Jordan W.
Brown, C. Hendricks
Huggins, Wayne
Hamilton, Carol
Haim, Adam
Farber, Gregory K.
TI Common Measures for National Institute of Mental Health Funded Research
SO BIOLOGICAL PSYCHIATRY
LA English
DT Editorial Material
ID DIFFICULTIES QUESTIONNAIRE SDQ; LIFE EVENTS QUESTIONNAIRE; SELF-REPORT
VERSION; PSYCHOMETRIC PROPERTIES; HIPPOCAMPAL VOLUMES; PHENX MEASURES;
CDE PROJECT; HIGH-RISK; STRENGTHS; PSYCHOSIS
C1 [Barch, Deanna M.] Washington Univ, Dept Psychol, Box 1125,One Brookings Dr, St Louis, MO 63130 USA.
[Barch, Deanna M.] Washington Univ, Dept Psychiat, Box 1125,One Brookings Dr, St Louis, MO 63130 USA.
[Barch, Deanna M.] Washington Univ, Dept Radiol, Box 1125,One Brookings Dr, St Louis, MO 63130 USA.
[Gotlib, Ian H.] Stanford Univ, Dept Psychol, Stanford, CA USA.
[Bilder, Robert M.] Univ Calif Los Angeles, Dept Psychiat, Los Angeles, CA USA.
[Bilder, Robert M.] Univ Calif Los Angeles, Dept Biobehav Sci & Psychol, Los Angeles, CA USA.
[Pine, Daniel S.] NIMH, Intramural Res Program, Bethesda, MD 20892 USA.
[Smoller, Jordan W.] Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Ctr Human Genet Res, Boston, MA 02114 USA.
[Smoller, Jordan W.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.
[Smoller, Jordan W.] Broad Inst, Stanley Ctr Psychiat Res, Boston, MA USA.
[Brown, C. Hendricks] Northwestern Univ, Dept Psychiat, Chicago, IL 60611 USA.
[Huggins, Wayne; Hamilton, Carol] RTI Int, Durham, NC USA.
[Haim, Adam] NIMH, Off Clin Res, Bethesda, MD 20892 USA.
[Farber, Gregory K.] NIMH, Off Technol Dev & Coordinat, Bethesda, MD 20892 USA.
RP Barch, DM (reprint author), Washington Univ, Dept Psychol, Box 1125,One Brookings Dr, St Louis, MO 63130 USA.; Barch, DM (reprint author), Washington Univ, Dept Psychiat, Box 1125,One Brookings Dr, St Louis, MO 63130 USA.; Barch, DM (reprint author), Washington Univ, Dept Radiol, Box 1125,One Brookings Dr, St Louis, MO 63130 USA.
EM dbarch@wustl.edu
OI Brown, C Hendricks/0000-0002-0294-2419
FU NHGRI NIH HHS [U41 HG007050]; NICHD NIH HHS [U54 HD087011]; NIMH NIH HHS
[K24 MH094614, R01 MH040859, R01 MH066031, R01 MH074849, R01 MH084840,
R01 MH090786, R01 MH098454, R01 MH101478, R01 MH101495, U54 MH091657]
NR 41
TC 0
Z9 0
U1 2
U2 8
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0006-3223
EI 1873-2402
J9 BIOL PSYCHIAT
JI Biol. Psychiatry
PD JUN 15
PY 2016
VL 79
IS 12
BP E91
EP E96
DI 10.1016/j.biopsych.2015.07.006
PG 6
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA DN0ZV
UT WOS:000376796500001
PM 26903402
ER
PT J
AU Patel, PR
Sun, W
Kim, M
Huang, XL
Sanderson, PE
Tanaka, TQ
Mckew, JC
Simeonov, A
Williamson, KC
Zheng, W
Huang, WW
AF Patel, Paresma R.
Sun, Wei
Kim, Myunghoon
Huang, Xiuli
Sanderson, Philip E.
Tanaka, Takeshi Q.
McKew, John C.
Simeonov, Anton
Williamson, Kim C.
Zheng, Wei
Huang, Wenwei
TI In vitro evaluation of imidazo[4,5-c]quinolin-2-ones as gametocytocidal
antimalarial agents
SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
LA English
DT Article
DE Antimalarial; Plasmodium falciparum; Gametocytes; Gametocytocidal;
Imidazo[4,5-c]quinolin-2-one
ID INHIBITOR; NVP-BEZ235
AB Novel imidazo[4,5-c] quinolin-2-ones were synthesized and evaluated in asexual blood stage and late stage gametocyte assays of Plasmodium falciparum, a major causative agent of malaria. The design of these compounds is based on a recently identified lead compound from a high throughput screen. A concise synthesis was developed that allowed for generation of analogues with substitution around both the quinoline and imidazolidinone rings. Through structure-activity relationship studies, a number of potent compounds were identified that possessed excellent antimalarial activity against both the asexual and sexual stages with minimal cytotoxicity in mammalian cells. This is the first Letter describing SAR and gametocytocidal activity of imidazo[4,5-c] quinolin-2-ones, a new lead series for malaria treatment and prevention. Published by Elsevier Ltd.
C1 [Patel, Paresma R.; Sun, Wei; Kim, Myunghoon; Huang, Xiuli; Sanderson, Philip E.; McKew, John C.; Simeonov, Anton; Zheng, Wei; Huang, Wenwei] NIH, Natl Ctr Adv Translat Sci, Bldg 10, Bethesda, MD 20892 USA.
[Tanaka, Takeshi Q.; Williamson, Kim C.] Loyola Univ, Dept Biol, Chicago, IL 60660 USA.
[Patel, Paresma R.] US FDA, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA.
[Tanaka, Takeshi Q.] Obihiro Univ Agr & Vet Med, Natl Res Ctr Protozoan Dis, Obihiro, Hokkaido 0808555, Japan.
[McKew, John C.] aTyr Pharma Inc, 3545 John Hopkins Court,Suite 250, San Diego, CA 92121 USA.
[Williamson, Kim C.] Uniformed Serv Univ Hlth Sci, Dept Microbiol & Immunol, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA.
RP Huang, WW (reprint author), NIH, Natl Ctr Adv Translat Sci, Bldg 10, Bethesda, MD 20892 USA.
EM huangwe@mail.nih.gov
RI Zheng, Wei/J-8889-2014
OI Zheng, Wei/0000-0003-1034-0757
FU National Center for Advancing Translational Sciences and Public Health
Service Grant from the National Institute of Allergy and Infectious
Diseases [AI101396]
FX The authors would like to thank Paul Shinn, Danielle VanLeer, and
Jennifer Bennison for assistance with compound management. This work was
supported by the Intramural Research Programs of the National Center for
Advancing Translational Sciences and Public Health Service Grant
AI101396 from the National Institute of Allergy and Infectious Diseases.
T.Q.T. is a JSPS Research Fellow in Biomedical and Behavioral Research
at the NIH.
NR 15
TC 2
Z9 2
U1 2
U2 2
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0960-894X
EI 1464-3405
J9 BIOORG MED CHEM LETT
JI Bioorg. Med. Chem. Lett.
PD JUN 15
PY 2016
VL 26
IS 12
BP 2907
EP 2911
DI 10.1016/j.bmcl.2016.04.045
PG 5
WC Chemistry, Medicinal; Chemistry, Organic
SC Pharmacology & Pharmacy; Chemistry
GA DN0BA
UT WOS:000376728200033
PM 27156776
ER
PT J
AU Gail, MH
Wu, JC
Wang, ML
Yaun, SS
Cook, NR
Eliassen, AH
McCullough, ML
Yu, K
Zeleniuch-Jacquotte, A
Smith-Warner, SA
Ziegler, RG
Carroll, RJ
AF Gail, Mitchell H.
Wu, Jincao
Wang, Molin
Yaun, Shiaw-Shyuan
Cook, Nancy R.
Eliassen, A. Heather
McCullough, Marjorie L.
Yu, Kai
Zeleniuch-Jacquotte, Anne
Smith-Warner, Stephanie A.
Ziegler, Regina G.
Carroll, Raymond J.
TI Calibration and seasonal adjustment for matched case-control studies of
vitamin D and cancer
SO STATISTICS IN MEDICINE
LA English
DT Article
DE calibration; seasonal adjustment; measurement error; matched
case-control study; molecular epidemiology; biomarkers
ID BREAST-CANCER; 25-HYDROXYVITAMIN D; D METABOLITES; SERUM-LEVELS; RISK
AB Vitamin D measurements are influenced by seasonal variation and specific assay used. Motivated by multicenter studies of associations of vitamin D with cancer, we formulated an analytic framework for matched case-control data that accounts for seasonal variation and calibrates to a reference assay. Calibration data were obtained from controls sampled within decile strata of the uncalibrated vitamin D values. Seasonal sine-cosine series were fit to control data. Practical findings included the following: (1) failure to adjust for season and calibrate increased variance, bias, and mean square error and (2) analysis of continuous vitamin D requires a variance adjustment for variation in the calibration estimate. An advantage of the continuous linear risk model is that results are independent of the reference date for seasonal adjustment. (3) For categorical risk models, procedures based on categorizing the seasonally adjusted and calibrated vitamin D have near nominal operating characteristics; estimates of log odds ratios are not robust to choice of seasonal reference date, however. Thus, public health recommendations based on categories of vitamin D should also define the time of year to which they refer. This work supports the use of simple methods for calibration and seasonal adjustment and is informing analytic approaches for the multicenter Vitamin D Pooling Project for Breast and Colorectal Cancer. Published 2016. This article has been contributed to by US Government employees and their work is in the public domain in the USA.
C1 [Gail, Mitchell H.; Yu, Kai; Ziegler, Regina G.] NCI, Div Canc Epidemiol & Genet, NIH, Rockville, MD USA.
[Wu, Jincao] Food & Drug Adm, Div Biostat, Ctr Devices & Radiol Hlth, Silver Spring, MD USA.
[Wang, Molin] Harvard Univ, Dept Biostat, TH Chan Sch Publ Hlth, Boston, MA USA.
[Wang, Molin; Cook, Nancy R.; Eliassen, A. Heather; Smith-Warner, Stephanie A.] Harvard Univ, Dept Epidemiol, TH Chan Sch Publ Hlth, Boston, MA USA.
[Yaun, Shiaw-Shyuan; Smith-Warner, Stephanie A.] Harvard Univ, Dept Nutr, TH Chan Sch Publ Hlth, Boston, MA USA.
[Cook, Nancy R.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Prevent Med, Boston, MA 02115 USA.
[Eliassen, A. Heather] Brigham & Womens Hosp, Dept Med, Med Network, Channing Div, 75 Francis St, Boston, MA 02115 USA.
[Eliassen, A. Heather] Harvard Univ, Sch Med, Boston, MA USA.
[McCullough, Marjorie L.] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA.
[Zeleniuch-Jacquotte, Anne] NYU, Sch Med, Dept Populat Hlth, New York, NY USA.
[Zeleniuch-Jacquotte, Anne] NYU, Sch Med, Perlmutter Canc Ctr, New York, NY USA.
[Carroll, Raymond J.] Texas A&M Univ, Dept Stat, College Stn, TX 77843 USA.
[Carroll, Raymond J.] Univ Technol Sydney, Dept Math & Stat, Sydney, NSW 2007, Australia.
RP Gail, MH (reprint author), NCI, Biostat Branch, 9609 Med Ctr Dr,Rm 7E-138, Rockville, MD 20850 USA.
EM gailm@mail.nih.gov
OI Cook, Nancy/0000-0002-9705-0842; Zeleniuch-Jacquotte,
Anne/0000-0001-9350-1303
FU Intramural Research Program of the National Cancer Institute, Division
of Cancer Epidemiology and Genetics; National Cancer Institute
[U01-CA057030, R01-CA098661, UM1-CA182934, P30-CA016087]; National
Institute of Environmental Health Sciences [ES000260]; American Cancer
Society; [R01-CA152071]
FX This work was supported by the Intramural Research Program of the
National Cancer Institute, Division of Cancer Epidemiology and Genetics.
Carroll's research was supported by a grant from the National Cancer
Institute (U01-CA057030). We thank Stephanie Weinstein, Demetrius
Albanes, and Michal Freedman for the use of ATBC and PLCO data; the
American Cancer Society for use of the CPSII data; Li Cheung for help
with R programming; and Mattias Johansson and David Muller for
assistance with the sine-cosine method for seasonal adjustment. The
American Cancer Society funded the creation, maintenance, and update of
the CPSII cohort. The NYUWHS is supported by the National Cancer
Institute (grants R01-CA098661, UM1-CA182934, and P30-CA016087) and by
the National Institute of Environmental Health Sciences (center grant
ES000260). The main Vitamin D Pooling Project was supported by
R01-CA152071.
NR 10
TC 1
Z9 1
U1 2
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0277-6715
EI 1097-0258
J9 STAT MED
JI Stat. Med.
PD JUN 15
PY 2016
VL 35
IS 13
BP 2133
EP 2148
DI 10.1002/sim.6856
PG 16
WC Mathematical & Computational Biology; Public, Environmental &
Occupational Health; Medical Informatics; Medicine, Research &
Experimental; Statistics & Probability
SC Mathematical & Computational Biology; Public, Environmental &
Occupational Health; Medical Informatics; Research & Experimental
Medicine; Mathematics
GA DL4LI
UT WOS:000375607200002
PM 27133461
ER
PT J
AU Sun, ZJ
Inskip, PD
Wang, JX
Kwon, D
Zhao, YC
Zhang, LA
Wang, Q
Fan, SJ
AF Sun, Zhijuan
Inskip, Peter D.
Wang, Jixian
Kwon, Deukwoo
Zhao, Yongcheng
Zhang, Liangan
Wang, Qin
Fan, Saijun
TI Solid cancer incidence among Chinese medical diagnostic x-ray workers,
1950-1995: Estimation of radiation-related risks
SO INTERNATIONAL JOURNAL OF CANCER
LA English
DT Article
DE medical X-ray workers; solid cancer; ionizing radiation; occupational
exposure; epidemiology; China
ID OCCUPATIONAL-EXPOSURE; DOSE RECONSTRUCTION; IONIZING-RADIATION; COHORT;
MORTALITY
AB The objective of this study was to estimate solid cancer risk attributable to long-term, fractionated occupational exposure to low doses of ionizing radiation. Based on cancer incidence for the period 1950-1995 in a cohort of 27,011 Chinese medical diagnostic X-ray workers and a comparison cohort of 25,782 Chinese physicians who did not use X-ray equipment in their work, we used Poisson regression to fit excess relative risk (ERR) and excess absolute risk (EAR) dose-response models for incidence of all solid cancers combined. Radiation dose reconstruction was based on a previously published method that relied on simulating measurements for multiple X-ray machines, workplaces and working conditions, information about protective measures, including use of lead aprons, and work histories. The resulting model was used to estimate calendar year-specific badge dose calibrated as personal dose equivalent (Sv). To obtain calendar year-specific colon doses (Gy), we applied a standard organ conversion factor. A total of 1,643 cases of solid cancer were identified in 1.45 million person-years of follow-up. In both ERR and EAR models, a statistically significant radiation dose-response relationship was observed for solid cancers as a group. Averaged over both sexes, and using colon dose as the dose metric, the estimated ERR/Gy was 0.87 (95% CI: 0.48, 1.45), and the EAR was 22 per 10(4)PY-Gy (95% CI: 14, 32) at age 50. We obtained estimates of the ERR and EAR of solid cancers per unit dose that are compatible with those derived from other populations chronically exposed to low dose-rate occupational or environmental radiation.
C1 [Sun, Zhijuan; Wang, Jixian; Zhao, Yongcheng; Zhang, Liangan; Wang, Qin; Fan, Saijun] Chinese Acad Med Sci, Tianjin Key Lab Radiat Med & Mol Nucl Med, Inst Radiat Med, Tianjin 300192, Peoples R China.
[Sun, Zhijuan; Wang, Jixian; Zhao, Yongcheng; Zhang, Liangan; Wang, Qin; Fan, Saijun] Peking Union Med Coll, Tianjin 300192, Peoples R China.
[Sun, Zhijuan; Inskip, Peter D.; Kwon, Deukwoo] NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Kwon, Deukwoo] Univ Miami, Sch Med, Silvestre Comprehens Canc Ctr, Miami, FL USA.
RP Wang, JX (reprint author), Peking Union Med Coll, Tianjin 300192, Peoples R China.; Wang, JX (reprint author), Chinese Acad Med Sci, Inst Radiat Med, Tianjin 300192, Peoples R China.
EM wangjixian@irm-cams.ac.cn
FU National Natural Science Foundation of China [81502760]; Institute of
Radiation Medicine, Peking Union Medical College (PUMC) & Chinese
Academy of Medical Sciences [SF1210]; PUMC Youth Fund; Fundamental
Research Funds for the Central Universities [33320140032]; Science
Research Foundation for Doctor-Subject of High School of the National
Education Department of China [20121106120041]; Intramural Research
Program of the National Institutes of Health; National Cancer Institute,
Department of Health and Human Services, USA, China Scholarship Council
FX Grant sponsor: National Natural Science Foundation of China; Grant
number: 81502760; Grant sponsor: Institute of Radiation Medicine, Peking
Union Medical College (PUMC) & Chinese Academy of Medical Sciences;
Grant number: SF1210; Grant sponsor: PUMC Youth Fund and the Fundamental
Research Funds for the Central Universities; Grant number: 33320140032;
Grant sponsor: Science Research Foundation for Doctor-Subject of High
School of the National Education Department of China; Grant number:
20121106120041; Grant sponsors: Intramural Research Program of the
National Institutes of Health and the National Cancer Institute,
Department of Health and Human Services, USA, China Scholarship Council
NR 28
TC 0
Z9 0
U1 3
U2 7
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0020-7136
EI 1097-0215
J9 INT J CANCER
JI Int. J. Cancer
PD JUN 15
PY 2016
VL 138
IS 12
BP 2875
EP 2883
DI 10.1002/ijc.30036
PG 9
WC Oncology
SC Oncology
GA DJ3XS
UT WOS:000374140600011
PM 26860236
ER
PT J
AU Norman, AI
Ivkov, R
Forbes, JG
Greer, SC
AF Norman, Alexander I.
Ivkov, Robert
Forbes, Jeffrey G.
Greer, Sandra C.
TI The polymerization of actin: Structural changes from small-angle neutron
scattering (vol 123, 154904, 2005)
SO JOURNAL OF CHEMICAL PHYSICS
LA English
DT Correction
ID FILAMENT
C1 [Norman, Alexander I.; Greer, Sandra C.] Univ Maryland, Dept Chem & Biochem, College Pk, MD 20742 USA.
[Norman, Alexander I.; Greer, Sandra C.] Univ Maryland, Dept Chem & Biomol Engn, College Pk, MD 20742 USA.
[Ivkov, Robert] Triton BioSyst Inc, Chelmsford, MA 01824 USA.
[Forbes, Jeffrey G.] Natl Inst Arthrit & Musculoskeletal & Skin Dis NI, Prote & Nanotechnol Sect, Muscle Biol Lab, NIH,DHHS, Bldg 50, Bethesda, MD 20892 USA.
[Norman, Alexander I.] ExxonMobil Chem Co, Global Chem Res, 5200 Bayway Dr, Baytown, TX 77520 USA.
[Ivkov, Robert] Johns Hopkins Univ, Dept Radiat Oncol & Mol Radiat Sci, Sch Med, Baltimore, MD 21231 USA.
[Forbes, Jeffrey G.] TWIC Inc, 4423 Lehigh Rd,172, College Pk, MD 20740 USA.
[Greer, Sandra C.] Mills Coll, Dept Chem, Oakland, CA 94613 USA.
RP Greer, SC (reprint author), Univ Maryland, Dept Chem & Biochem, College Pk, MD 20742 USA.; Greer, SC (reprint author), Univ Maryland, Dept Chem & Biomol Engn, College Pk, MD 20742 USA.
EM sgreer@umd.edu
NR 11
TC 0
Z9 0
U1 0
U2 2
PU AMER INST PHYSICS
PI MELVILLE
PA 1305 WALT WHITMAN RD, STE 300, MELVILLE, NY 11747-4501 USA
SN 0021-9606
EI 1089-7690
J9 J CHEM PHYS
JI J. Chem. Phys.
PD JUN 14
PY 2016
VL 144
IS 22
AR 229902
DI 10.1063/1.4953362
PG 2
WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical
SC Chemistry; Physics
GA DQ0XW
UT WOS:000378926100040
PM 27306026
ER
PT J
AU Shoffner, J
Trommer, B
Thurm, A
Farmer, C
Langley, WA
Soskey, L
Rodriguez, AN
D'Souza, P
Spence, SJ
Hyland, K
Swedo, SE
AF Shoffner, John
Trommer, Barbara
Thurm, Audrey
Farmer, Cristan
Langley, William A., III
Soskey, Laura
Rodriguez, Aldeboran N.
D'Souza, Precilla
Spence, Sarah J.
Hyland, Keith
Swedo, Susan E.
TI CSF concentrations of 5-methyltetrahydrofolate in a cohort of young
children with autism
SO NEUROLOGY
LA English
DT Article
ID CEREBRAL FOLATE-DEFICIENCY; KEARNS-SAYRE SYNDROME; CEREBROSPINAL-FLUID;
AUTOANTIBODIES; POPULATION; DISORDERS; SPECTRUM; DISEASES; UTILITY; CNS
AB Objective:To examine the association between cerebral folate deficiency and autism, this study examined CSF 5-methyltetrahydrofolate (5-MTHF) concentrations in a group of young children with autism, investigated the natural variation in CSF 5-MTHF over time, and assessed the relationship between CSF 5-MTHF and symptoms.Methods:CSF was collected from 67 children with a diagnosis of DSM-IV-TR autistic disorder (age, mean SD 43 11 months), with a second CSF sample obtained 1-3 years later on 31 of these subjects (time to follow-up, 30 +/- 8 months).Results:At time 1, 7% (5/67) of participants had 5-MTHF <40 nmol/L. At follow-up, 23% (7/31) of participants had 5-MTHF <40 nmol/L (only one of whom had been low at time 1). A moderate correlation with a very wide confidence interval (CI) was observed between time 1 and time 2 CSF 5-MTHF measurements (Pearson r[p] = 0.38 [0.04]; 95% CI 0.02-0.64). Neither the CSF 5-MTHF levels nor changes over time correlated with the clinical features of autism.Conclusions:CSF 5-MTHF levels vary significantly over time in an unpredictable fashion and do not show a significant relationship to typical clinical features of autism. Reduced CSF 5-MTHF levels are a nonspecific finding in autism. Our data do not support the use of lumbar puncture for assessment of CSF 5-MTHF in autism.
C1 [Shoffner, John; Langley, William A., III; Hyland, Keith] Georgia State Univ, Med Neurogenet, Atlanta, GA 30303 USA.
[Shoffner, John] Georgia State Univ, Atlanta, GA 30303 USA.
[Trommer, Barbara; Thurm, Audrey; Farmer, Cristan; Soskey, Laura; Rodriguez, Aldeboran N.; D'Souza, Precilla; Spence, Sarah J.; Swedo, Susan E.] NIMH, Pediat & Dev Neurosci Branch, NIH, Bethesda, MD 20892 USA.
[Trommer, Barbara] Suny Downstate Med Ctr, Brooklyn, NY 11203 USA.
[Spence, Sarah J.] Boston Childrens Hosp, Dept Neurol, Boston, MA USA.
RP Swedo, SE (reprint author), NIMH, Pediat & Dev Neurosci Branch, NIH, Bethesda, MD 20892 USA.
EM swedos@mail.nih.gov
FU National Institute of Mental Health of the National Institutes of Health
[NCT00298246, 06-M-0102, ZIA MH002914]; Department of Defense
[W81XWH-09-1-0367, W81XWH-10-1-0547]
FX Supported by the Intramural Program of the National Institute of Mental
Health of the National Institutes of Health, NCT00298246, 06-M-0102, and
ZIA MH002914. John Shoffner, MD, William A. Langley, III, PhD, and Keith
Hyland, PhD, were supported by the Department of Defense under award
numbers W81XWH-09-1-0367 and W81XWH-10-1-0547. Views and opinions of and
endorsements by the author(s) do not reflect those of the US Army, the
Department of Defense, NIMH, NIH, HHS, or the United States Government.
NR 29
TC 2
Z9 2
U1 3
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0028-3878
EI 1526-632X
J9 NEUROLOGY
JI Neurology
PD JUN 14
PY 2016
VL 86
IS 24
BP 2258
EP 2263
DI 10.1212/WNL.0000000000002766
PG 6
WC Clinical Neurology
SC Neurosciences & Neurology
GA DP8AT
UT WOS:000378721000013
PM 27178705
ER
PT J
AU Sacchetti, B
Funari, A
Remoli, C
Giannicola, G
Kogler, G
Liedtke, S
Cossu, G
Serafini, M
Sampaolesi, M
Tagliafico, E
Tenedini, E
Saggio, I
Robey, PG
Riminucci, M
Bianco, P
AF Sacchetti, Benedetto
Funari, Alessia
Remoli, Cristina
Giannicola, Giuseppe
Kogler, Gesine
Liedtke, Stefanie
Cossu, Giulio
Serafini, Marta
Sampaolesi, Maurilio
Tagliafico, Enrico
Tenedini, Elena
Saggio, Isabella
Robey, Pamela G.
Riminucci, Mara
Bianco, Paolo
TI No Identical "Mesenchymal Stem Cells'' at Different Times and Sites:
Human Committed Progenitors of Distinct Origin and Differentiation
Potential Are Incorporated as Adventitial Cells in Microvessels
SO STEM CELL REPORTS
LA English
DT Article
ID SKELETAL-MUSCLE; STROMAL CELLS; CORD BLOOD; HEMATOPOIETIC NICHE;
SATELLITE CELLS; SOURCES REVEALS; SMOOTH-MUSCLE; DORSAL AORTA; PDGF-B;
PERICYTES
AB A widely shared view reads that mesenchymal stem/stromal cells (''MSCs'') are ubiquitous in human connective tissues, can be defined by a common in vitro phenotype, share a skeletogenic potential as assessed by in vitro differentiation assays, and coincide with ubiquitous pericytes. Using stringent in vivo differentiation assays and transcriptome analysis, we show that human cell populations from different anatomical sources, regarded as ''MSCs'' based on these criteria and assumptions, actually differ widely in their transcriptomic signature and in vivo differentiation potential. In contrast, they share the capacity to guide the assembly of functional microvessels in vivo, regardless of their anatomical source, or in situ identity as perivascular or circulating cells. This analysis reveals that muscle pericytes, which are not spontaneously osteochondrogenic as previously claimed, may indeed coincide with an ectopic perivascular subset of committed myogenic cells similar to satellite cells. Cord blood-derived stromal cells, on the other hand, display the unique capacity to form cartilage in vivo spontaneously, in addition to an assayable osteogenic capacity. These data suggest the need to revise current misconceptions on the origin and function of so-called ''MSCs,'' with important applicative implications. The data also support the view that rather than a uniform class of ''MSCs,'' different mesoderm derivatives include distinct classes of tissue-specific committed progenitors, possibly of different developmental origin.
C1 [Sacchetti, Benedetto; Funari, Alessia; Remoli, Cristina; Riminucci, Mara; Bianco, Paolo] Univ Roma La Sapienza, Stem Cell Lab, Dept Mol Med, I-00161 Rome, Italy.
[Giannicola, Giuseppe] Univ Roma La Sapienza, Dept Anat Histol Forens Med & Orthoped Sci, I-00158 Rome, Italy.
[Kogler, Gesine; Liedtke, Stefanie] Univ Dusseldorf, Inst Transplant Diagnost & Cellular Therapeut, Med Ctr, D-40225 Dusseldorf, Germany.
[Cossu, Giulio] Univ Manchester, Inst Inflammat & Repair, Manchester M13 9PL, Lancs, England.
[Serafini, Marta] Univ Milano Bicocca, San Gerardo Hosp, Tettamanti Res Ctr, Dept Pediat,Dulbecco Telethon Inst, I-20900 Monza, Italy.
[Sampaolesi, Maurilio] Katholieke Univ Leuven, Dept Dev & Regenerat, B-3000 Leuven, Belgium.
[Tagliafico, Enrico; Tenedini, Elena] Univ Modena & Reggio Emilia, Ctr Genome Res, I-41121 Modena, Italy.
[Saggio, Isabella] Univ Roma La Sapienza, Dept Biol & Biotechnol C Darwin, IBPM CNR, I-00185 Rome, Italy.
[Robey, Pamela G.] Natl Inst Dent & Craniofacial Res, Craniofacial & Skeletal Dis Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
RP Riminucci, M (reprint author), Univ Roma La Sapienza, Stem Cell Lab, Dept Mol Med, I-00161 Rome, Italy.; Robey, PG (reprint author), Natl Inst Dent & Craniofacial Res, Craniofacial & Skeletal Dis Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
EM probey@dir.nidcr.nih.gov; mara.riminucci@uniroma1.it
RI Robey, Pamela/H-1429-2011; Tagliafico, Enrico/C-9079-2009;
OI Robey, Pamela/0000-0002-5316-5576; Tagliafico,
Enrico/0000-0003-0981-2542; Cossu, Giulio/0000-0001-5863-9593; TENEDINI,
Elena/0000-0003-0285-765X
FU Telethon [GGP09227, TCP07004]; MIUR; Fondazione Cenci Bolognetti;
Ministry of Health of Italy; EU (PluriMes consortium)
[FP7-HEALTH-2013-INNOVATION-1-G.A. 602423]; Sapienza University of Rome;
Fondazione Roma; Bilateral grant [DFG-KO2119/8-1]; DIR; NIDCR, of the
IRP; NIH; DHHS
FX Sadly, Prof. Paolo Bianco passed away while this manuscript was in
revision. We dedicate this study to him, for all of his outstanding
contributions throughout the years, and his complete dedication to
bringing clarity to this area of research. This work was supported by
Telethon (Grant GGP09227), MIUR, Fondazione Cenci Bolognetti, Ministry
of Health of Italy, EU (PluriMes consortium,
FP7-HEALTH-2013-INNOVATION-1-G.A. 602423), Sapienza University of Rome
to P.B.; Fondazione Roma to P.B. and M.R.; Bilateral grant
DFG-KO2119/8-1 to P.B. and G.K.; by Telethon (Grant TCP07004) to M.S.;
and by DIR, NIDCR, of the IRP, NIH, DHHS to P.G.R.
NR 43
TC 8
Z9 8
U1 1
U2 5
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 2213-6711
J9 STEM CELL REP
JI Stem Cell Rep.
PD JUN 14
PY 2016
VL 6
IS 6
BP 897
EP 913
DI 10.1016/j.stemcr.2016.05.011
PG 17
WC Cell & Tissue Engineering; Cell Biology
SC Cell Biology
GA DO8KQ
UT WOS:000378032600012
PM 27304917
ER
PT J
AU Deschamps, JD
Ogunsola, AF
Jameson, JB
Yasgar, A
Flitter, BA
Freedman, CJ
Melvin, JA
Nguyen, JVMH
Maloney, DJ
Jadhav, A
Simeonov, A
Bomberger, JM
Holman, TR
AF Deschamps, Joshua D.
Ogunsola, Abiola F.
Jameson, J. Brian, II
Yasgar, Adam
Flitter, Becca A.
Freedman, Cody J.
Melvin, Jeffrey A.
Nguyen, Jason V. M. H.
Maloney, David J.
Jadhav, Ajit
Simeonov, Anton
Bomberger, Jennifer M.
Holman, Theodore R.
TI Biochemical and Cellular Characterization and Inhibitor Discovery of
Pseudomonas aeruginosa 15-Lipoxygenase
SO BIOCHEMISTRY
LA English
DT Article
ID AIRWAY EPITHELIAL-CELLS; EARLY CYSTIC-FIBROSIS; SOYBEAN LIPOXYGENASE-1;
SELECTIVE INHIBITORS; BIOFILM FORMATION; ARACHIDONATE 15-LIPOXYGENASE;
STRUCTURAL INVESTIGATIONS; BRONCHOALVEOLAR LAVAGE;
SUBSTRATE-SPECIFICITY; HUMAN RETICULOCYTE
AB Pseudomonas aeruginosa is an opportunistic pathogen that can cause nosocomial and chronic infections in immunotompromised patients. P. aeruginosa secretes a lipoxygenase, LoxA, but the biological role of this enzyme is-currently unknown. LoxA is poorly similar in sequence to both soybean LOX-1 (s15-LOX-1) and human 15-LOX-1 (37 and, 39%, respectively) yet has kinetics comparably fast versus these of s15-LOX-1 (at pH 6.5, K-cat, = 181 +/- 6 s(-1) and K-cat/K-m.716 +/- 2 mu M-1 s(-1)). LoxA is capable of efficiently catalyzing the peroxidation of a broad range of free fatty acid (FA) substrates.(e.g., AA and LA) with high positional specificity, indicating a 15-LOX. Its mechanism includes hydrogen atom abstraction [a kinetic isotope effect (KIE) of >30], yet LoxA. is a poor catalyst against phosphoester FAs, suggesting that LoxA is not involved in membrane decomposition. LoxA also does not react with 5- or 15-HETEs, indicating poor involvement in lipoxin production. A LOX high-throughput screen of the LOPAC library yielded a variety of low-micromolar inhibitors; however, none selectively targeted Loth over the human LOX isozymes. With respect to cellular activity, the level of LoxA expression is increased when P. aeruginosa undergoes the transition to a biofilin mode of growth, but LoxA is not required for biofilm growth on abiotic surfaces. However, LoxA does appear to be required for biofilm growth in association with the-host airway epithelium, suggesting, a role for LoxA in mediating bacterium-host interactions during, colonization.
C1 [Deschamps, Joshua D.; Jameson, J. Brian, II; Freedman, Cody J.; Nguyen, Jason V. M. H.; Holman, Theodore R.] Univ Calif Santa Cruz, Dept Chem & Biochem, Santa Cruz, CA 95064 USA.
[Ogunsola, Abiola F.; Flitter, Becca A.; Melvin, Jeffrey A.; Bomberger, Jennifer M.] Univ Pittsburgh, Dept Microbiol & Mol Genet, Pittsburgh, PA 15219 USA.
[Yasgar, Adam; Maloney, David J.; Jadhav, Ajit; Simeonov, Anton] NIH, Natl Ctr Adv Translat Sci, 9800 Med Ctr Dr,MSC 3370, Bethesda, MD 20892 USA.
RP Holman, TR (reprint author), Univ Calif Santa Cruz, Dept Chem & Biochem, Santa Cruz, CA 95064 USA.; Bomberger, JM (reprint author), Univ Pittsburgh, Dept Microbiol & Mol Genet, Pittsburgh, PA 15219 USA.
EM jbomb@pitt.edu; tholman@chemistry.ucsc.edu
FU National Institutes of Health [GM56062, S10-RR20939, R00HL098342,
T32AI49820]; Gilead Research Scholars in Cystic Fibrosis Grant; Cystic
Fibrosis Foundation (CFF) [MELVIN15F0]; National Center for Advancing
Translational Sciences; National Science Foundation [CHE-1427922]
FX This work was supported by the National Institutes of Health [GM56062
and S10-RR20939 (T.R.H.), R00HL098342 (J.M.B.), and T32AI49820
(J.A.M.)], a Gilead Research Scholars in Cystic Fibrosis Grant (J.M.B.),
the Cystic Fibrosis Foundation (CFF, MELVIN15F0), the intramural
research program of the National Center for Advancing Translational
Sciences (A.Y., D.J.M., A.J., and A.S.), and the National Science
Foundation (MS equipment grant CHE-1427922).
NR 61
TC 2
Z9 2
U1 3
U2 6
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0006-2960
J9 BIOCHEMISTRY-US
JI Biochemistry
PD JUN 14
PY 2016
VL 55
IS 23
BP 3329
EP 3340
DI 10.1021/acs.biochem.6b00338
PG 12
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA DO8EX
UT WOS:000378016500016
PM 27226387
ER
PT J
AU Davis, SK
Xu, RH
Riestra, P
Gebreab, SY
Khan, RJ
Gaye, A
Hickson, D
Sims, M
Bidulescu, A
AF Davis, Sharon K.
Xu, Ruihua
Riestra, Pia
Gebreab, Samson Y.
Khan, Rumana J.
Gaye, Amadou
Hickson, DeMarc
Sims, Mario
Bidulescu, Aurelian
TI Association of adiponectin and socioeconomic status in African American
men and women: the Jackson heart study
SO BMC PUBLIC HEALTH
LA English
DT Article
DE Biomarkers; Cardiovascular disease; Socioeconomic status; Adiponectin;
African Americans
ID C-REACTIVE PROTEIN; CARDIOVASCULAR-DISEASE; RISK-FACTORS; EDUCATION;
MARKERS; HYPERTENSION; INFLAMMATION; PREVALENCE; FIBRINOGEN; GLUCOSE
AB Background: Recent emphasis has been placed on elucidating the biologic mechanism linking socioeconomic status (SES) to cardiovascular disease (CVD). Positive associations of inflammatory biomarkers provide evidence suggestive of a biologic pathway by which SES may predispose to CVD. African Americans have disproportionately lower SES and have a higher prevalence of CVD risk factors compared to most ethnic/racial groups. Adiponectin (an anti-inflammatory marker) is also lower. The objective of this study was to assess the association of adiponectin with SES among African American men and women using the Jackson Heart Study.
Methods: Study sample included 4340 participants. Linear regression was performed separately by SES and stratified by sex. Annual household income and level of education was used as proxies for SES. Crude, age, health behavior and health status adjusted models were analyzed. The main outcome was log-transformed adiponectin.
Results: Men in the lowest income group had significantly higher adiponectin than those in the highest income group in the fully adjusted model (beta/standard error [se], p value = .16/.08, p = .0008. Men with < high school level of education had significantly higher adiponectin in the crude and age adjusted models than those with = college degree (.25/.05, p < .0001; .14/.05/ p = .005, respectively). Women with some college or vocational training in the crude and age adjusted models had lower adiponectin compared to women with = college degree (-.09/.03, p = .004; -.06/.03, p = .04, respectively).
Conclusion: Findings suggest a potential inverse biologic pathway between annual household income and adiponectin among African American men. There was no such finding among women. Findings suggest interventions should be targeted for higher SES African American men to improve adiponectin levels.
C1 [Davis, Sharon K.; Xu, Ruihua; Riestra, Pia; Gebreab, Samson Y.; Khan, Rumana J.; Gaye, Amadou] NHGRI, Social Epidemiol Res Unit, NIH, 10 Ctr Dr,Room 7 N320,MSC 1644, Bethesda, MD 20892 USA.
[Hickson, DeMarc; Sims, Mario] Univ Mississippi, Med Ctr, Jackson, MS 39216 USA.
[Bidulescu, Aurelian] Indiana Univ, Sch Publ Hlth, Bloomington, IN 47405 USA.
RP Davis, SK (reprint author), NHGRI, Social Epidemiol Res Unit, NIH, 10 Ctr Dr,Room 7 N320,MSC 1644, Bethesda, MD 20892 USA.
EM sharon.davis@nih.gov
OI Gaye, Amadou/0000-0002-1180-2792
FU National Heart, Lung and Blood Institute and the National Institute on
Minority Health and Health Disparities [HHSN268201200046C,
HHSN26820120047C, HHSM268201300048C, HHSN26820130049C,
HHSN268201300050C]; PHS Award from the National Center for Research
Resources [UL1RR025008]; National Heart, Lung and Blood Institute
[UH1HL073461]; intramural program of the National Human Genome Research
Institute, National Institutes of Health; National Human Genome Research
Institute
FX The authors would like to thank the staff and the participants of the
Jackson Heart Study for their valuable contributions. Funding for the
Jackson Heart Study was supported by contracts HHSN268201200046C,
HHSN26820120047C, HHSM268201300048C, HHSN26820130049C, HHSN268201300050C
from the National Heart, Lung and Blood Institute and the National
Institute on Minority Health and Health Disparities. The adiponectin
measurements were partially supported by PHS Award UL1RR025008 from the
National Center for Research Resources and by grant UH1HL073461 from the
National Heart, Lung and Blood Institute. Sharon K. Davis, Ruihua Xu,
Pia Riestra, Samson Y. Gebreab, Rumana J. Khan and Amadou Gaye are
supported by the intramural program of the National Human Genome
Research Institute, National Institutes of Health. The National Human
Genome Research Institute supported the design and conduct of the study,
management of analyses, interpretation of the data, review and approval
of the manuscript. Sharon K. Davis had full access to all the data in
the study and takes responsibility for the integrity of the data and the
accuracy of the data analysis. The authors have no disclosures to
report.
NR 31
TC 0
Z9 0
U1 0
U2 1
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2458
J9 BMC PUBLIC HEALTH
JI BMC Public Health
PD JUN 14
PY 2016
VL 16
AR 511
DI 10.1186/s12889-016-3167-x
PG 11
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA DO3WX
UT WOS:000377714300002
PM 27301295
ER
PT J
AU Mera, P
Laue, K
Ferron, M
Confavreux, C
Wei, JW
Galan-Diez, M
Lacampagne, A
Mitchell, SJ
Mattison, JA
Chen, Y
Bacchetta, J
Szulc, P
Kitsis, RN
de Cabo, R
Friedman, RA
Torsitano, C
McGraw, TE
Puchowicz, M
Kurland, I
Karsenty, G
AF Mera, Paula
Laue, Kathrin
Ferron, Mathieu
Confavreux, Cyril
Wei, Jianwen
Galan-Diez, Marta
Lacampagne, Alain
Mitchell, Sarah J.
Mattison, Julie A.
Chen, Yun
Bacchetta, Justine
Szulc, Pawel
Kitsis, Richard N.
de Cabo, Rafael
Friedman, Richard A.
Torsitano, Christopher
McGraw, Timothy E.
Puchowicz, Michelle
Kurland, Irwin
Karsenty, Gerard
TI Osteocalcin Signaling in Myofibers Is Necessary and Sufficient for
Optimum Adaptation to Exercise
SO CELL METABOLISM
LA English
DT Article
ID SKELETAL-MUSCLE CONTRACTION; AMPK PHOSPHORYLATION; ENERGY-METABOLISM;
INSULIN; GLUCOSE; INTERLEUKIN-6; DISTINCT; BONE; MECHANISMS; EXPRESSION
AB Circulating levels of undercarboxylated and bioactive osteocalcin double during aerobic exercise at the time levels of insulin decrease. In contrast, circulating levels of osteocalcin plummet early during adulthood in mice, monkeys, and humans of both genders. Exploring these observations revealed that osteocalcin signaling in myofibers is necessary for adaptation to exercise by favoring uptake and catabolism of glucose and fatty acids, the main nutrients of myofibers. Osteocalcin signaling in myofibers also accounts for most of the exercise-induced release of interleukin-6, a myokine that promotes adaptation to exercise in part by driving the generation of bioactive osteocalcin. We further show that exogenous osteocalcin is sufficient to enhance the exercise capacity of young mice and to restore to 15-month-old mice the exercise capacity of 3-month-old mice. This study uncovers a bone-tomuscle feedforward endocrine axis that favors adaptation to exercise and can reverse the age-induced decline in exercise capacity.
C1 [Mera, Paula; Laue, Kathrin; Ferron, Mathieu; Wei, Jianwen; Karsenty, Gerard] Columbia Univ, Med Ctr, Dept Genet & Dev, New York, NY 10032 USA.
[Confavreux, Cyril; Bacchetta, Justine; Szulc, Pawel] Univ Lyon, Hosp Civils Lyon, INSERM, UMR1033, F-69003 Lyon, France.
[Galan-Diez, Marta] Columbia Univ, Med Ctr, Dept Physiol & Cellular Biophys, New York, NY 10032 USA.
[Lacampagne, Alain] Univ Montpellier, CHRU Montpellier, CNRS, INSERM,UMR 9214,U1046, F-34295 Montpellier 5, France.
[Mitchell, Sarah J.; Mattison, Julie A.; de Cabo, Rafael] NIA, Translat Gerontol Branch, NIH, Baltimore, MD 21224 USA.
[Chen, Yun; Kitsis, Richard N.] Yeshiva Univ Albert Einstein Coll Med, Dept Cell Biol, Dept Med Cardiol, 1300 Morris Pk Ave, Bronx, NY 10461 USA.
[Chen, Yun; Kitsis, Richard N.] Yeshiva Univ Albert Einstein Coll Med, Wilf Family Cardiovasc Res Inst, Bronx, NY 10461 USA.
[Friedman, Richard A.] Columbia Univ, Med Ctr, Dept Biomed Informat, New York, NY 10032 USA.
[Torsitano, Christopher; McGraw, Timothy E.] Cornell Univ, Weill Med Coll, Dept Biochem, New York, NY 10065 USA.
[Puchowicz, Michelle] Case Western Reserve Univ, Sch Med, Dept Nutr, Cleveland, OH 44106 USA.
[Kurland, Irwin] Yeshiva Univ Albert Einstein Coll Med, Dept Med, 1300 Morris Pk Ave, Bronx, NY 10461 USA.
[Ferron, Mathieu] Inst Rech Clin Montreal, Integrat & Mol Physiol Res Unit, Montreal, PQ H2W 1R7, Canada.
RP Karsenty, G (reprint author), Columbia Univ, Med Ctr, Dept Genet & Dev, New York, NY 10032 USA.
EM gk2172@cumc.columbia.edu
RI de Cabo, Rafael/J-5230-2016;
OI de Cabo, Rafael/0000-0002-3354-2442; , rafael/0000-0003-2830-5693
FU NIH [5RO1AR045548, PO1AG032959, P60DK020541, RO1HL60665, U24DK76174];
Wilf Family Foundation; Ellison Senior Scholar Award; EMBO postdoctoral
fellowship; National Institute on Aging
FX We thank Drs. C. Cosentino, P. Ducy, L. Herrero, M. Hussain, R. Sellers,
D. Serra, and E. Sornay-Rendu for advice or reagents, and Dr. M. McKee
for electronic microscopy analyses. This work was supported by NIH
grants 5RO1AR045548, PO1AG032959 (G.K.), P60DK020541 (I.K.), RO1HL60665
(R.N.K.), and U24DK76174 (M.P.); the Wilf Family Foundation (R.N.K.); an
Ellison Senior Scholar Award (G.K.); an EMBO postdoctoral fellowship
(K.L.); and the Intramural Research Program of the National Institute on
Aging (R.dC., S.J.M., and J.A.M.).
NR 47
TC 10
Z9 11
U1 2
U2 10
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1550-4131
EI 1932-7420
J9 CELL METAB
JI Cell Metab.
PD JUN 14
PY 2016
VL 23
IS 6
BP 1078
EP 1092
DI 10.1016/j.cmet.2016.05.004
PG 15
WC Cell Biology; Endocrinology & Metabolism
SC Cell Biology; Endocrinology & Metabolism
GA DO7ZA
UT WOS:000378000600020
PM 27304508
ER
PT J
AU Mitchell, SJ
Madrigal-Matute, J
Scheibye-Knudsen, M
Fang, E
Aon, M
Gonzalez-Reyes, JA
Cortassa, S
Kaushik, S
Gonzalez-Freire, M
Patel, B
Wahl, D
Ali, A
Calvo-Rubio, M
Buron, MI
Guiterrez, V
Ward, TM
Palacios, HH
Cai, H
Frederick, DW
Hine, C
Broeskamp, F
Habering, L
Dawson, J
Beasley, TM
Wan, JX
Ikeno, Y
Hubbard, G
Becker, KG
Zhang, YQ
Bohr, VA
Longo, DL
Navas, P
Ferrucci, L
Sinclair, DA
Cohen, P
Egan, JM
Mitchell, JR
Baur, JA
Allison, DB
Anson, RM
Villalba, JM
Madeo, F
Cuervo, AM
Pearson, KJ
Ingram, DK
Bernier, M
de Cabo, R
AF Mitchell, Sarah J.
Madrigal-Matute, Julio
Scheibye-Knudsen, Morten
Fang, Evandro
Aon, Miguel
Gonzalez-Reyes, Jose A.
Cortassa, Sonia
Kaushik, Susmita
Gonzalez-Freire, Marta
Patel, Bindi
Wahl, Devin
Ali, Ahmed
Calvo-Rubio, Miguel
Buron, Maria I.
Guiterrez, Vincent
Ward, Theresa M.
Palacios, Hector H.
Cai, Huan
Frederick, David W.
Hine, Christopher
Broeskamp, Filomena
Habering, Lukas
Dawson, John
Beasley, T. Mark
Wan, Junxiang
Ikeno, Yuji
Hubbard, Gene
Becker, Kevin G.
Zhang, Yongqing
Bohr, Vilhelm A.
Longo, Dan L.
Navas, Placido
Ferrucci, Luigi
Sinclair, David A.
Cohen, Pinchas
Egan, Josephine M.
Mitchell, James R.
Baur, Joseph A.
Allison, David B.
Anson, R. Michael
Villalba, Jose M.
Madeo, Frank
Cuervo, Ana Maria
Pearson, Kevin J.
Ingram, Donald K.
Bernier, Michel
de Cabo, Rafael
TI Effects of Sex, Strain, and Energy Intake on Hallmarks of Aging in Mice
SO CELL METABOLISM
LA English
DT Article
ID GENETICALLY HETEROGENEOUS MICE; EXTENDS LIFE-SPAN; CHAPERONE-MEDIATED
AUTOPHAGY; DIFFERENT DIETARY FATS; SHORT-TERM CALORIE; BODY-MASS INDEX;
RHESUS-MONKEYS; NORDIHYDROGUAIARETIC ACID; MITOCHONDRIAL BIOGENESIS;
CAENORHABDITIS-ELEGANS
AB Calorie restriction (CR) is the most robust non-genetic intervention to delay aging. However, there are a number of emerging experimental variables that alter CR responses. We investigated the role of sex, strain, and level of CR on health and survival in mice. CR did not always correlate with lifespan extension, although it consistently improved health across strains and sexes. Transcriptional and metabolomics changes driven by CR in liver indicated anaplerotic filling of the Krebs cycle together with fatty acid fueling of mitochondria. CR prevented ageassociated decline in the liver proteostasis network while increasing mitochondrial number, preserving mitochondrial ultrastructure and function with age. Abrogation of mitochondrial function negated life-prolonging effects of CR in yeast and worms. Our data illustrate the complexity of CR in the context of aging, with a clear separation of outcomes related to health and survival, highlighting complexities of translation of CR into human interventions.
C1 [Mitchell, Sarah J.; Scheibye-Knudsen, Morten; Gonzalez-Freire, Marta; Wahl, Devin; Ali, Ahmed; Guiterrez, Vincent; Ward, Theresa M.; Palacios, Hector H.; Ferrucci, Luigi; Anson, R. Michael; Pearson, Kevin J.; Bernier, Michel; de Cabo, Rafael] NIA, Translat Gerontol Branch, Intramural Res Program, NIH, 251 Bayview Blvd,Suite 100, Baltimore, MD 21224 USA.
[Madrigal-Matute, Julio; Kaushik, Susmita; Patel, Bindi; Cuervo, Ana Maria] Albert Einstein Coll Med, Inst Aging Studies, Dept Dev & Mol Biol, Bronx, NY 10461 USA.
[Scheibye-Knudsen, Morten; Fang, Evandro; Bohr, Vilhelm A.] NIA, Lab Mol Gerontol, Intramural Res Program, NIH, 251 Bayview Blvd,Suite 100, Baltimore, MD 21224 USA.
[Scheibye-Knudsen, Morten] Univ Copenhagen, Dept Cellular & Mol Med, Ctr Hlth Aging, DK-2200 Copenhagen, Denmark.
[Aon, Miguel; Cortassa, Sonia] NIA, Lab Cardiovasc Sci, Intramural Res Program, NIH, 251 Bayview Blvd,Suite 100, Baltimore, MD 21224 USA.
[Gonzalez-Reyes, Jose A.; Calvo-Rubio, Miguel; Buron, Maria I.; Villalba, Jose M.] Univ Cordoba, Dept Cell Biol Physiol & Immunol, Agrifood Campus Int Excellence,CeiA3, E-14071 Cordoba, Spain.
[Cai, Huan; Egan, Josephine M.] NIA, Lab Clin Invest, Intramural Res Program, NIH, 251 Bayview Blvd,Suite 100, Baltimore, MD 21224 USA.
[Frederick, David W.; Baur, Joseph A.] Univ Penn, Dept Physiol, Inst Diabet Obes & Metab, Philadelphia, PA 19104 USA.
[Hine, Christopher; Mitchell, James R.] Harvard Univ, Dept Genet & Complex Dis, Boston, MA 02115 USA.
[Broeskamp, Filomena; Habering, Lukas; Madeo, Frank] Graz Univ, NAWI Graz, Inst Mol Biosci, A-8010 Graz, Austria.
[Broeskamp, Filomena; Habering, Lukas; Madeo, Frank] BioTechMed Graz, A-8010 Graz, Austria.
[Dawson, John; Beasley, T. Mark; Allison, David B.] Univ Alabama Birmingham, Dept Biostat, Birmingham, AL 35294 USA.
[Dawson, John; Beasley, T. Mark; Allison, David B.] Birmingham Atlanta Vet Adm Hosp, GRECC, Birmingham, AL 35294 USA.
[Wan, Junxiang; Cohen, Pinchas] Univ So Calif, Leonard Davis Sch Gerontol, Los Angeles, CA 90089 USA.
[Ikeno, Yuji; Hubbard, Gene] Univ Texas Hlth Sci Ctr San Antonio, Barshop Inst Longev & Aging Studies, San Antonio, TX 78245 USA.
[Becker, Kevin G.; Zhang, Yongqing; Longo, Dan L.] NIA, Lab Genet, Intramural Res Program, NIH, 251 Bayview Blvd,Suite 100, Baltimore, MD 21224 USA.
[Navas, Placido] Univ Pablo de Olavide, CSIC, Ctr Andaluz Biol Desarrollo, Seville 41013, Spain.
[Navas, Placido] Univ Pablo de Olavide, CIBERER, Inst Salud Carlos III, Seville 41013, Spain.
[Sinclair, David A.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
[Pearson, Kevin J.] Univ Kentucky, Grad Ctr Nutr Sci, CT Wethington Bldg,Room 591,900 South Limestone, Lexington, KY 40536 USA.
[Ingram, Donald K.] Pennington Biomed Res Ctr, Baton Rouge, LA 70809 USA.
RP de Cabo, R (reprint author), NIA, Translat Gerontol Branch, Intramural Res Program, NIH, 251 Bayview Blvd,Suite 100, Baltimore, MD 21224 USA.
EM decabora@mail.nih.gov
RI de Cabo, Rafael/J-5230-2016; Aon, Miguel/A-6564-2008;
OI de Cabo, Rafael/0000-0002-3354-2442; Aon, Miguel/0000-0002-4355-5431;
Scheibye-Knudsen, Morten/0000-0002-6637-1280; Gonzalez-Reyes, Jose
A./0000-0003-1918-5490; , rafael/0000-0003-2830-5693
FU Intramural Research Program of the National Institute on Aging, NIH; NIH
[R01 AG043483, R01 DK098656, AG031782, 1P01AG034906, 1R01GM090311,
1R01ES 020812]; Proteostasis of Aging Core [AG038072]; American Diabetes
Association [1-15-MI-03]; FWF [I1000, P27893, P29203, P24381-B20]; BMWFW
[80.109/0001-WF/V/3b/2015]; Spanish Ministerio de Economia y
Competitividad [BFU2011-23578, BFU2015-64630-R]
FX This work was supported in part by the Intramural Research Program of
the National Institute on Aging, NIH, and by NIH grants R01 AG043483 and
R01 DK098656 (J.A.B.), NIH grant AG031782 (A.M.C.), and the Proteostasis
of Aging Core AG038072 (A.M.C.). J.M.M. was supported by a postdoctoral
fellowship from the American Diabetes Association, grant 1-15-MI-03.
P.C. was supported by NIH grants (1P01AG034906, 1R01GM090311, and 1R01ES
020812). F.M. is grateful to the FWF for grants LIPOTOX, I1000, P27893,
P29203, and P24381-B20 and the BMWFW for grants "Unconventional
Research" and "Flysleep" (80.109/0001-WF/V/3b/2015). J.M.V. was
supported by the Spanish Ministerio de Economia y Competitividad (grants
BFU2011-23578 and BFU2015-64630-R). The authors thank the personnel from
the Servicio Centralizado de Apoyo a la Investigacion (SCAI; University
of Cordoba) for technical support. Special thanks to the members of the
Translational Gerontology Branch and the Comparative Medicine Section of
the National Institute on Aging. In particular we acknowledge Paul
Bastian, Elin Lehrmann, Frances Fan, Robin Minor, Dawn Nines, and Dawn
Boyer.
NR 115
TC 4
Z9 4
U1 4
U2 6
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1550-4131
EI 1932-7420
J9 CELL METAB
JI Cell Metab.
PD JUN 14
PY 2016
VL 23
IS 6
BP 1093
EP 1112
DI 10.1016/j.cmet.2016.05.027
PG 20
WC Cell Biology; Endocrinology & Metabolism
SC Cell Biology; Endocrinology & Metabolism
GA DO7ZA
UT WOS:000378000600021
PM 27304509
ER
PT J
AU Sciolino, NR
Plummer, NW
Chen, YW
Alexander, GM
Robertson, SD
Dudek, SM
McElligott, ZA
Jensen, P
AF Sciolino, Natale R.
Plummer, Nicholas W.
Chen, Yu-Wei
Alexander, Georgia M.
Robertson, Sabrina D.
Dudek, Serena M.
McElligott, Zoe A.
Jensen, Patricia
TI Recombinase-Dependent Mouse Lines for Chemogenetic Activation of
Genetically Defined Cell Types
SO CELL REPORTS
LA English
DT Article
ID LOCUS-COERULEUS NEURONS; SITE-SPECIFIC RECOMBINATION; PROTEIN-COUPLED
RECEPTORS; EMBRYONIC STEM-CELLS; MAMMALIAN-CELLS; MICE; CRE; TRANSGENES;
MODULATION; EXPRESSION
AB Chemogenetic technologies, including the mutated human Gq-coupled M3 muscarinic receptor (hM3Dq), have greatly facilitated our ability to directly link changes in cellular activity to altered physiology and behavior. Here, we extend the hM3Dq toolkit with recombinase-responsive mouse lines that permit hM3Dq expression in virtually any cell type. These alleles encode a fusion protein designed to increase effective expression levels by concentrating hM3Dq to the cell body and dendrites. To illustrate their broad utility, we targeted three different genetically defined cell populations: noradrenergic neurons of the compact, bilateral locus coeruleus and two dispersed populations, Camk2a+ neurons and GFAP+ glia. In all three populations, we observed reproducible expression and confirmed that activation of hM3Dq is sufficient to dose-dependently evoke phenotypic changes, without extreme phenotypes associated with hM3Dq overexpression. These alleles offer the ability to non-invasively control activity of diverse cell types to uncover their function and dysfunction at any developmental stage.
C1 [Sciolino, Natale R.; Plummer, Nicholas W.; Chen, Yu-Wei; Alexander, Georgia M.; Dudek, Serena M.; Jensen, Patricia] NIEHS, Neurobiol Lab, Dept Hlth & Human Serv, NIH, Res Triangle Pk, NC 27709 USA.
[Robertson, Sabrina D.] N Carolina State Univ, Biotechnol Program, Dept Mol Biomed Sci, Raleigh, NC 27695 USA.
[McElligott, Zoe A.] Univ N Carolina, Sch Med, Bowles Ctr Alcohol Studies, Chapel Hill, NC 27514 USA.
[McElligott, Zoe A.] Univ N Carolina, Sch Med, Dept Psychiat, Chapel Hill, NC 27514 USA.
RP Jensen, P (reprint author), NIEHS, Neurobiol Lab, Dept Hlth & Human Serv, NIH, Res Triangle Pk, NC 27709 USA.
EM patricia.jensen@nih.gov
FU Intramural Research Program of the NIH, NIEHS [ES102805, ES100221]
FX We thank D. D'Agostin, G. Jones, and K. Smith for technical assistance.
We thank B. Roth (University of North Carolina) for providing the
hM3Dq-mCherry-2ACT88 cDNA. We also thank J. Haam, C. Erxleben, C. Hull
(Duke University), and D. Weinshenker (Emory University) for helpful
advice. Valuable support was provided by the NIEHS Comparative Medicine
Branch, Knockout Mouse Core, Biostatistics and Computational Biology
Branch, and Fluorescence Microscopy and Imaging Core. We thank the NIDA
Drug Supply Program for providing the CNO. This research was supported
by the Intramural Research Program of the NIH, NIEHS (ES102805 to P.J.
and ES100221 to S.M.D.).
NR 30
TC 0
Z9 0
U1 1
U2 7
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 2211-1247
J9 CELL REP
JI Cell Reports
PD JUN 14
PY 2016
VL 15
IS 11
BP 2563
EP 2573
DI 10.1016/j.celrep.2016.05.034
PG 11
WC Cell Biology
SC Cell Biology
GA DO4TG
UT WOS:000377776400023
PM 27264177
ER
PT J
AU Mitter, SS
Vedanthan, R
Islami, F
Pourshams, A
Khademi, H
Kamangar, F
Abnet, CC
Dawsey, SM
Pharoah, PD
Brennan, P
Fuster, V
Boffetta, P
Malekzadeh, R
AF Mitter, Sumeet S.
Vedanthan, Rajesh
Islami, Farhad
Pourshams, Akram
Khademi, Hooman
Kamangar, Farin
Abnet, Christian C.
Dawsey, Sanford M.
Pharoah, Paul D.
Brennan, Paul
Fuster, Valentin
Boffetta, Paolo
Malekzadeh, Reza
TI Household Fuel Use and Cardiovascular Disease Mortality Golestan Cohort
Study
SO CIRCULATION
LA English
DT Article
DE air pollution; epidemiology; heart diseases; mortality; stroke
ID DIESEL-EXHAUST INHALATION; INDOOR AIR-POLLUTION; WOOD SMOKE EXPOSURE;
LONG-TERM EXPOSURE; BLOOD-PRESSURE; ESOPHAGEAL CANCER; BIOMASS FUEL;
WOMEN; INTERVENTION; COOKING
AB Background-Household air pollution is the third largest risk factor for global disease burden, but direct links with cardiovascular disease mortality are limited. This study aimed to evaluate the relationship between household fuel use and cardiovascular disease mortality.
Methods and Results-The Golestan Cohort Study in northeastern Iran enrolled 50 045 individuals 40 to 75 years of age between 2004 and 2008 and collected data on lifetime household fuel use and other baseline exposures. Participants were followed up through 2012 with a 99% successful follow-up rate. Cox proportional hazards models were fitted to calculate hazard ratios for associations between pehen (local dung), wood, kerosene/diesel, or natural gas burning for cooking and heating and all-cause and cause-specific mortality, with adjustment for lifetime exposure to each of these fuels and potential confounders. A total of 3073 participants (6%) died during follow-up; 78% of these deaths were attributable to noncommunicable diseases, including cardiovascular, oncological, and respiratory illnesses. Adjusted 10-year hazard ratios from kerosene/diesel burning were 1.06 (95% confidence interval, 1.02-1.10) and 1.11 (95% confidence interval, 1.06-1.17) for all-cause and cardiovascular mortality, respectively. Subtype-specific analyses revealed a significant increase in ischemic heart disease (10-year hazard ratio, 1.14; 95% confidence interval, 1.06-1.21) and a trend toward cerebrovascular accident (10-year hazard ratio, 1.08; 95% confidence interval, 0.99-1.17) mortality. Stratification by sex revealed a potential signal for increased risk for all-cause and cardiovascular disease mortality among women compared with men, with similar risk for ischemic heart disease mortality.
Conclusions-Household exposure to high-pollution fuels was associated with increased risk for all-cause and cardiovascular disease mortality. Replicating these results worldwide would support efforts to reduce such exposures.
C1 [Mitter, Sumeet S.] Northwestern Univ, Feinberg Sch Med, Dept Med, Div Cardiol, 676 N St Clair St,Ste 600, Chicago, IL 60611 USA.
[Vedanthan, Rajesh; Fuster, Valentin] Icahn Sch Med Mt Sinai, Zena & Michael A Wiener Cardiovasc Inst, New York, NY 10029 USA.
[Islami, Farhad; Brennan, Paul] Icahn Sch Med Mt Sinai, Tisch Canc Inst, New York, NY 10029 USA.
[Islami, Farhad; Brennan, Paul] Icahn Sch Med Mt Sinai, Inst Translat Epidemiol, New York, NY 10029 USA.
[Islami, Farhad; Pourshams, Akram; Malekzadeh, Reza] Univ Tehran Med Sci, Digest Dis Res Inst, Digest Oncol Res Ctr, Tehran, Iran.
[Islami, Farhad] Amer Canc Soc, Surveillance & Hlth Serv Res, Atlanta, GA 30329 USA.
[Khademi, Hooman; Brennan, Paul] Int Agcy Res Canc, 150 Cours Albert Thomas, F-69372 Lyon, France.
[Kamangar, Farin] Morgan State Univ, Sch Community Hlth & Policy, Dept Publ Hlth Anal, Baltimore, MD 21239 USA.
[Abnet, Christian C.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Pharoah, Paul D.] Univ Cambridge, Dept Oncol, Cambridge CB2 1TN, England.
[Pharoah, Paul D.] Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge CB2 1TN, England.
[Fuster, Valentin] Ctr Nacl Invest Cardiovasc, Madrid, Spain.
[Boffetta, Paolo] Int Prevent Res Inst, Lyon, France.
RP Mitter, SS (reprint author), Northwestern Univ, Feinberg Sch Med, Dept Med, Div Cardiol, 676 N St Clair St,Ste 600, Chicago, IL 60611 USA.
EM sumeet.mitter@northwestern.edu
RI Abnet, Christian/C-4111-2015; Fuster, Valentin/H-4319-2015
OI Abnet, Christian/0000-0002-3008-7843; Fuster,
Valentin/0000-0002-9043-9986
FU Tehran University of Medical Sciences (Tehran, Iran) [81/15]; Cancer
Research UK (London, UK) [C20/A5860]; US National Cancer Institute
(Bethesda, MD); International Agency for Research on Cancer (Lyon,
France); Fogarty International Center of the National Institutes of
Health (Bethesda, MD) [K01 TW 009218-05]
FX The Golestan Cohort Study was funded by Tehran University of Medical
Sciences (grant 81/15, Tehran, Iran), by Cancer Research UK (grant
C20/A5860, London, UK), by the Intramural Research Program of the US
National Cancer Institute (Bethesda, MD), and through various
collaborative research agreements with the International Agency for
Research on Cancer (Lyon, France). Dr Vedanthan receives grant funding
from the Fogarty International Center of the National Institutes of
Health (K01 TW 009218-05, Bethesda, MD). The content is solely the
responsibility of the authors and does not necessarily represent the
official views of the National Institutes of Health.
NR 39
TC 2
Z9 2
U1 5
U2 10
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0009-7322
EI 1524-4539
J9 CIRCULATION
JI Circulation
PD JUN 14
PY 2016
VL 133
IS 24
BP 2360
EP +
DI 10.1161/CIRCULATIONAHA.115.020288
PG 23
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA DO8PI
UT WOS:000378045100009
PM 27297340
ER
PT J
AU McCracken, ML
Gorini, G
McCracken, LM
Mayfield, RD
Harris, RA
Trudell, JR
AF McCracken, Mandy L.
Gorini, Giorgio
McCracken, Lindsay M.
Mayfield, R. Dayne
Harris, R. Adron
Trudell, James R.
TI Inter- and Intra-Subunit Butanol/Isoflurane Sites of Action in the Human
Glycine Receptor
SO FRONTIERS IN MOLECULAR NEUROSCIENCE
LA English
DT Article
DE GLRA1; alcohol; anesthetic; Xenopus oocytes; GluCl model;
massspectrometry; immunoblotting; proteomics
ID GATED ION CHANNELS; ACID TYPE-A; ANESTHETIC BINDING-SITE; GABA(A)
RECEPTOR; CROSS-LINKING; TRANSMEMBRANE DOMAIN; GENERAL-ANESTHETICS;
ACETYLCHOLINE-RECEPTOR; CHLORIDE CHANNEL; STRUCTURAL BASIS
AB Glycine receptors (GlyRs) mediate inhibitory neurotransmission and are targets for alcohols and anesthetics in brain. GlyR transmembrane (TM) domains contain critical residues for alcohol/anesthetic action: amino acid A288 in TM3 forms crosslinks with TM1 (1229) in the adjacent subunit as well as TM2 (S267) and TM4 (Y406, W407, 1409, Y410) in the same subunit. We hypothesized that these residues may participate in intra-subunit and inter-subunit sites of alcohol/anesthetic action. The following double and triple mutants of GLRA1 cDNA (encoding human glycine receptor alpha 1 subunit) were injected into)Aenopus laevis oocytes: I229C/A288C, 1229C/A288C/C290S, A288C/Y406C, A288C/W407C, A288C/1409C, and A288C/Y410C along with the corresponding single mutants and wild-type GLRA1. Butanol (22 mM) or isoflurane (0.6 mM) potentiation of GlyR-mediated currents before and after application of the cysteine crosslinking agent HgCL2 (10 mu M) was measured using two-electrode voltage clamp electrophysiology. Crosslinking nearly abolished butanol and isoflurane potentiation in the I229C/A288C and 1229C/A288C/C290S mutants but had no effect in single mutants or wild-type. Crosslinking also inhibited butanol and isoflurane potentiation in the TM3-4 mutants (A288C/Y406C, A288C/W407C, A288C/1409C, A288C/Y410C) with no effect in single mutants or wild-type. We extracted proteins from oocytes expressing I229C/288C, A288C/Y410C, or wild-type GlyRs, used mass spectrometry to verify their expression and possible inter-subunit dimerization, plus immunoblotting to investigate the biochemical features of proposed crosslinks. Wild-type GlyR subunits measured about 50 kDa; after crosslinking, the dimeric/monomeric 100:50 kDa band ratio was significantly increased in I229C/288C but not A288C/Y410C mutants or wild-type, providing support for TM1-3 inter-subunit and TM3-4 intra-subunit crosslinking. A GlyR homology model based on the GluCl template provides further evidence for a multi-site model for alcohol/anesthetic interaction with human GLRA1.
C1 [McCracken, Mandy L.; Gorini, Giorgio; McCracken, Lindsay M.; Mayfield, R. Dayne; Harris, R. Adron] Univ Texas Austin, Waggoner Ctr Alcohol & Addict Res, Austin, TX 78712 USA.
[McCracken, Mandy L.] NIDA, Integrat Neurosci Res Branch, Neurobiol Addict Sect, NIH, Baltimore, MD USA.
[Trudell, James R.] Stanford Sch Med, Dept Anesthesia, Stanford, CA USA.
[Trudell, James R.] Stanford Sch Med, Beckman Program Mol & Genet Med, Stanford, CA USA.
RP Harris, RA (reprint author), Univ Texas Austin, Waggoner Ctr Alcohol & Addict Res, Austin, TX 78712 USA.
EM harris@austin.utexas.edu
RI Gorini, Giorgio/D-7053-2014
OI Gorini, Giorgio/0000-0002-0893-5922
FU National Institutes of Health, National Institute on Alcohol Abuse and
Alcoholism [R01 AA013378, R37 AA006399, R01 AA020980, U01 AA016648, U01
AA0209260]
FX This work was supported by the National Institutes of Health, National
Institute on Alcohol Abuse and Alcoholism (grants R01 AA013378; R37
AA006399; R01 AA020980; U01 AA016648; U01 AA0209260).
NR 63
TC 0
Z9 0
U1 3
U2 7
PU FRONTIERS MEDIA SA
PI LAUSANNE
PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015,
SWITZERLAND
SN 1662-5099
J9 FRONT MOL NEUROSCI
JI Front. Molec. Neurosci.
PD JUN 14
PY 2016
VL 9
AR 45
DI 10.3389/fnmol.2016.00045
PG 13
WC Neurosciences
SC Neurosciences & Neurology
GA DO3WT
UT WOS:000377713900001
PM 27378846
ER
PT J
AU Lerner, ZF
Browning, RC
AF Lerner, Zachary F.
Browning, Raymond C.
TI Compressive and shear hip joint contact forces are affected by pediatric
obesity during walking
SO JOURNAL OF BIOMECHANICS
LA English
DT Article
DE Obesity; Gait biomechanics; Musculoskeletal modeling; Personalized;
Joint loading; OpenSim; Orthopedics
ID MUSCULOSKELETAL PAIN; PHYSICAL-ACTIVITY; LOWER-EXTREMITY; MUSCLE
FUNCTION; BONE GEOMETRY; CHILDREN; ADOLESCENTS; GAIT; OVERWEIGHT;
KINEMATICS
AB Obese children exhibit altered gait mechanics compared to healthy-weight children and have an increased prevalence of hip pain and pathology. This study sought to determine the relationships between body mass and compressive and shear hip joint contact forces during walking. Kinematic and kinetic data were collected during treadmill walking at 1 m s(-1) in 10 obese and 10 healthy-weight 8-12 year-olds. We estimated body composition, segment masses, lower-extremity alignment, and femoral neck angle via radiographic images, created personalized musculoskeletal models in OpenSim, and computed muscle forces and hip joint contact forces. Hip extension at mid-stance was 9 degrees less, on average, in the obese children (p < 0.001). Hip abduction, knee flexion, and body-weight normalized peak hip moments were similar between groups. Normalized to body-weight, peak contact forces were similar at the first peak and slightly lower at the second peak between the obese and healthy-weight participants. Total body mass explained a greater proportion of contact force variance compared to lean body mass in the compressive (r(2)=0.89) and vertical shear (perpendicular to the physic acting superior-to-inferior) (r(2)=0.84) directions; lean body mass explained a greater proportion in the posterior shear direction (r(2)=0.54). Stance-average contact forces in the compressive and vertical shear directions increased by 41 N and 48 N, respectively, for every kilogram of body mass. Age explained less than 27% of the hip loading variance. No effect of sex was found. The proportionality between hip loads and body-weight may be implicated in an obese child's increased risk of hip pain and pathology. Published by Elsevier Ltd.
C1 [Lerner, Zachary F.] NIH, Funct & Appl Biomech Sect, Dept Rehabil Med, Bethesda, MD 20892 USA.
[Lerner, Zachary F.; Browning, Raymond C.] Colorado State Univ, Sch Biomed Engn, Ft Collins, CO 80523 USA.
[Browning, Raymond C.] Colorado State Univ, Dept Hlth & Exercise Sci, Ft Collins, CO 80523 USA.
RP Lerner, ZF (reprint author), NIH, Funct & Appl Biomech Sect, Dept Rehabil Med, CRC, Bldg 10,Room 1-1469,MSC 1604, Bethesda, MD 20892 USA.
EM Zachary.Lerner@nih.gov
FU Eunice Kennedy Shriver National Institute of Child Health & Human
Development of the National Institutes of Health [F31HD080261]; ACSM
Foundation Research Grant from the American College of Sports Medicine
FX This research was supported by the Eunice Kennedy Shriver National
Institute of Child Health & Human Development of the National Institutes
of Health under Award Number F31HD080261 and by an ACSM Foundation
Research Grant from the American College of Sports Medicine. We thank
the Medical Center of the Rockies Healthy Hearts program for their
assistance in participant recruitment. We also thank all of the
researchers associated with Orthoload for making their valuable datasets
publically available.
NR 30
TC 0
Z9 0
U1 5
U2 9
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0021-9290
EI 1873-2380
J9 J BIOMECH
JI J. Biomech.
PD JUN 14
PY 2016
VL 49
IS 9
BP 1547
EP 1553
DI 10.1016/j.jbiomech.2016.03.033
PG 7
WC Biophysics; Engineering, Biomedical
SC Biophysics; Engineering
GA DO4DE
UT WOS:000377731200020
PM 27040390
ER
PT J
AU Liu, HP
Kurtoglu, M
Leon-Annicchiarico, CL
Munoz-Pinedo, C
Barredo, J
Leclerc, G
Merchan, J
Liu, XF
Lampidis, TJ
AF Liu, Huaping
Kurtoglu, Metin
Lucia Leon-Annicchiarico, Clara
Munoz-Pinedo, Cristina
Barredo, Julio
Leclerc, Guy
Merchan, Jaime
Liu, Xiongfei
Lampidis, Theodore J.
TI Combining 2-deoxy-D-glucose with fenofibrate leads to tumor cell death
mediated by simultaneous induction of energy and ER stress
SO ONCOTARGET
LA English
DT Article
DE 2-deoxy-D-glucose; fenofibrate; energy stress; mTOR; eIF2 alpha
ID GLYCOLYTIC INHIBITOR 2-DEOXY-D-GLUCOSE; ENDOPLASMIC-RETICULUM;
METABOLISM; GLYCOSYLATION; CYTOTOXICITY; INCREASES; APOPTOSIS; EFFICACY;
CANCERS
AB Unregulated growth and replication as well as an abnormal microenvironment, leads to elevated levels of stress which is a common trait of cancer. By inducing both energy and endoplasmic reticulum (ER) stress, 2-Deoxy-glucose (2-DG) is particularly well-suited to take advantage of the therapeutic window that heightened stress in tumors provides. Under hypoxia, blocking glycolysis with 2-DG leads to significant lowering of ATP resulting in energy stress and cell death in numerous carcinoma cell types. In contrast, under normoxia, 2-DG at a low-concentration is not toxic in most carcinomas tested, but induces growth inhibition, which is primarily due to ER stress. Here we find a synergistic toxic effect in several tumor cell lines in vitro combining 2-DG with fenofibrate (FF), a drug that has been safely used for over 40 years to lower cholesterol in patients. This combination induces much greater energy stress than either agent alone, as measured by ATP reduction, increased p-AMPK and downregulation of mTOR. Inhibition of mTOR results in blockage of GRP78 a critical component of the unfolded protein response which we speculate leads to greater ER stress as observed by increased p-eIF2 alpha. Moreover, to avoid an insulin response and adsorption by the liver, 2-DG is delivered by slow-release pump yielding significant anti-tumor control when combined with FF. Our results provide promise for developing this combination clinically and others that combine 2-DG with agents that act synergistically to selectively increase energy and ER stress to a level that is toxic to numerous tumor cell types.
C1 [Liu, Huaping; Liu, Xiongfei; Lampidis, Theodore J.] Univ Miami, Miller Sch Med, Dept Cell Biol, Miami, FL 33136 USA.
[Liu, Huaping; Barredo, Julio; Leclerc, Guy; Merchan, Jaime; Liu, Xiongfei; Lampidis, Theodore J.] Sylvester Comprehens Canc Ctr, Miami, FL USA.
[Kurtoglu, Metin] NIH, Bldg 10, Bethesda, MD 20892 USA.
[Lucia Leon-Annicchiarico, Clara; Munoz-Pinedo, Cristina] IDIBELL Bellvitage Biomed Res Inst, Cell Death Regulat Grp, Barcelona, Spain.
[Barredo, Julio; Leclerc, Guy] Univ Miami, Miller Sch Med, Dept Pediat, Miami, FL 33136 USA.
[Merchan, Jaime] Univ Miami, Miller Sch Med, Dept Med, Miami, FL 33136 USA.
RP Lampidis, TJ (reprint author), Univ Miami, Miller Sch Med, Dept Cell Biol, Miami, FL 33136 USA.; Lampidis, TJ (reprint author), Sylvester Comprehens Canc Ctr, Miami, FL USA.
EM tlampidi@miami.edu
RI Munoz-Pinedo, Cristina/B-6118-2008
OI Munoz-Pinedo, Cristina/0000-0002-9120-664X
NR 27
TC 1
Z9 1
U1 2
U2 3
PU IMPACT JOURNALS LLC
PI ALBANY
PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA
SN 1949-2553
J9 ONCOTARGET
JI Oncotarget
PD JUN 14
PY 2016
VL 7
IS 24
BP 36461
EP 36473
DI 10.18632/oncotarget.9263
PG 13
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA DO4MJ
UT WOS:000377756800075
PM 27183907
ER
PT J
AU Kaye, DR
Pinto, PA
Cecchi, F
Reilly, J
Semerjian, A
Rabe, DC
Gupta, G
Choyke, PL
Bottaro, DP
AF Kaye, Deborah R.
Pinto, Peter A.
Cecchi, Fabiola
Reilly, Joseph
Semerjian, Alice
Rabe, Daniel C.
Gupta, Gopal
Choyke, Peter L.
Bottaro, Donald P.
TI Tumor and Plasma Met Levels in Non-Metastatic Prostate Cancer
SO PLOS ONE
LA English
DT Article
ID HEPATOCYTE GROWTH-FACTOR; C-MET; BONE METASTASES; ANTIGEN LEVEL;
PROGRESSION; EXPRESSION; RECEPTOR; CABOZANTINIB; CARCINOMA; LOCATION
AB Objective
To measure Met protein content in prostate biopsies guided by fused magnetic resonance and ultrasound imaging, and to measure soluble Met (sMet) protein concentration in plasma samples from patients presenting evidence of prostate cancer.
Patients and Methods
345 patients had plasma samples drawn prior to image-guided biopsy of the prostate. Of these, 32% had benign biopsies. Of the 236 that were positive for prostate adenocarcinoma (PCa), 132 treated by total prostatectomy had Gleason scores of 6 (17%), 7, (55%), 8 (16%), or 9-10 (12%). 23% had evidence of local invasion. Plasma samples were also obtained from 80 healthy volunteers. Tissue Met and plasma sMet were measured by two-site immunoassay; values were compared among clinically defined groups using non-parametric statistical tests to determine significant differences or correlations.
Results
PCa tumor Met correlated significantly with plasma sMet, but median values were similar among benign and malignant groups. Median plasma sMet values were also similar among those groups, although both medians were significantly above normal. Median Met content in primary PCa tumors and sMet concentrations were independent of Gleason score, final pathologic stage and age.
Conclusion
Plasma sMet is not predictive of PCa or its severity in patients with organ-confined or locally invasive disease. Quantitative analysis of Met protein content and activation state in PCa tumor biopsy samples was highly feasible and may have value in follow-up to genomic and/or transcriptomic-based screens that show evidence of oncogenically relevant MET gene features that occur at relatively low frequency in non-metastatic PCa.
C1 [Kaye, Deborah R.; Pinto, Peter A.; Cecchi, Fabiola; Reilly, Joseph; Semerjian, Alice; Rabe, Daniel C.; Gupta, Gopal; Bottaro, Donald P.] NCI, Urol Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Choyke, Peter L.] NCI, Mol Imaging Program, Ctr Canc Res, Bethesda, MD 20892 USA.
[Kaye, Deborah R.] Johns Hopkins Univ, James Buchanan Brady Urol Inst, 600 N Wolfe St, Baltimore, MD 21287 USA.
[Cecchi, Fabiola; Reilly, Joseph] NantOmics, 9600 Med Ctr Dr,Suite 300, Rockville, MD 20850 USA.
[Semerjian, Alice] George Washington Univ Med Fac Associates, 2150 Penn Ave NW, Washington, DC 20037 USA.
[Rabe, Daniel C.] Univ Chicago, Div Biol Sci, BSLC, 924 E 57th St,Suite 104, Chicago, IL 60637 USA.
[Gupta, Gopal] Loyola Univ, Med Ctr, Dept Urol, 2160 S First Ave,Bldg 54,Room 237A, Maywood, IL 60153 USA.
RP Bottaro, DP (reprint author), NCI, Urol Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
EM dbottaro@helix.nih.gov
FU Intramural Research Program of the NIH, National Cancer Institute,
Center for Cancer Research; National Institutes of Health Intramural
Research Program, National Cancer Institute, Center for Cancer Research
[ZIA BC011124]
FX This work was funded by the National Institutes of Health Intramural
Research Program, National Cancer Institute, Center for Cancer Research,
awarded to DPB, ZIA BC011124:
http://fundedresearch.cancer.gov/nciportfolio/search/detailsaction=abstr
act&grantNum=ZIA%20BC%20011124&grantID=34045&grtSCDC=FY%202013&absID=340
45&absSCDC=PUB2013. The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.; This work was supported by the Intramural Research Program
of the NIH, National Cancer Institute, Center for Cancer Research. We
thank Alessio Giubellino for contributions to Met measurements reported
here.
NR 28
TC 1
Z9 1
U1 1
U2 1
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUN 14
PY 2016
VL 11
IS 6
AR e0157130
DI 10.1371/journal.pone.0157130
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DO5KO
UT WOS:000377822200030
PM 27300295
ER
PT J
AU Lee, ES
Vedanthan, R
Jeemon, P
Kamano, JH
Kudesia, P
Rajan, V
Engelgau, M
Moran, AE
AF Lee, Edward S.
Vedanthan, Rajesh
Jeemon, Panniyammakal
Kamano, Jemima H.
Kudesia, Preeti
Rajan, Vikram
Engelgau, Michael
Moran, Andrew E.
TI Quality Improvement for Cardiovascular Disease Care in Low- and
Middle-Income Countries: A Systematic Review
SO PLOS ONE
LA English
DT Review
ID CLUSTER-RANDOMIZED-TRIAL; ACUTE CORONARY SYNDROMES; RHEUMATIC
HEART-DISEASE; HEALTH-INSURANCE; CLINICAL-TRIAL; BLOOD-PRESSURE;
RISK-FACTORS; SECONDARY PREVENTION; POLYPILL POLYCAP; PEER SUPPORT
AB Background
The majority of global cardiovascular disease (CVD) burden falls on people living in low- and middle-income countries (LMICs). In order to reduce preventable CVD mortality and morbidity, LMIC health systems and health care providers need to improve the delivery and quality of CVD care.
Objectives
As part of the Disease Control Priorities Three (DCP3) Study efforts addressing quality improvement, we reviewed and summarized currently available evidence on interventions to improve quality of clinic-based CVD prevention and management in LMICs.
Methods
We conducted a narrative review of published comparative clinical trials that evaluated efficacy or effectiveness of clinic-based CVD prevention and management quality improvement interventions in LMICs. Conditions selected a priori included hypertension, diabetes, hyperlipidemia, coronary artery disease, stroke, rheumatic heart disease, and congestive heart failure. MEDLINE and EMBASE electronic databases were systematically searched. Studies were categorized as occurring at the system or patient/provider level and as treating the acute or chronic phase of CVD.
Results
From 847 articles identified in the electronic search, 49 met full inclusion criteria and were selected for review. Selected studies were performed in 19 different LMICs. There were 10 studies of system level quality improvement interventions, 38 studies of patient/provider interventions, and one study that fit both criteria. At the patient/provider level, regardless of the specific intervention, intensified, team-based care generally led to improved medication adherence and hypertension control. At the system level, studies provided evidence that introduction of universal health insurance coverage improved hypertension and diabetes control. Studies of system and patient/provider level acute coronary syndrome quality improvement interventions yielded inconclusive results. The duration of most studies was less than 12 months.
Conclusions
The results of this review suggest that CVD care quality improvement can be successfully implemented in LMICs. Most studies focused on chronic CVD conditions; more acute CVD care quality improvement studies are needed. Longer term interventions and follow-up will be needed in order to assess the sustainability of quality improvement efforts in LMICs.
C1 [Lee, Edward S.] Univ So Calif, Keck Sch Med, Dept Med, Palliat & Gen Internal Med,Div Geriatr, Los Angeles, CA 90033 USA.
[Vedanthan, Rajesh] Icahn Sch Med Mt Sinai, Div Cardiol, Dept Med, New York, NY 10029 USA.
[Jeemon, Panniyammakal] Publ Hlth Fdn India, Ctr Control Chron Condit, Cochin, Kerala, India.
[Kamano, Jemima H.] Moi Univ, Coll Hlth Sci, Eldoret, Kenya.
[Kamano, Jemima H.] Acad Model Providing Access Healthcare, Eldoret, Kenya.
[Kudesia, Preeti] World Bank, Hlth Nutr & Populat Global Practice, Kathmandu, Nepal.
[Rajan, Vikram] World Bank, Jakarta, Indonesia.
[Engelgau, Michael] NHLBI, Ctr Translat Res & Implementat Sci, NIH, Bldg 10, Bethesda, MD 20892 USA.
[Moran, Andrew E.] Columbia Univ, Div Gen Med, Dept Med, Med Ctr, New York, NY USA.
RP Moran, AE (reprint author), Columbia Univ, Div Gen Med, Dept Med, Med Ctr, New York, NY USA.
EM aem35@cumc.columbia.edu
FU U.S. National Heart, Lung and Blood Institute career development award
[K08 HL089675-01]; Fogarty International Center of the U.S. National
Institutes of Health [K01 TW 009218-05]; Department of Biotechnology
India Alliance clinical and public health intermediate career
fellowship; Wellcome Trust
FX AEM was supported by a grant from the U.S. National Heart, Lung and
Blood Institute career development award (K08 HL089675-01;
www.nhlbi.nih.gov). RV was supported by a grant from the Fogarty
International Center of the U.S. National Institutes of Health (K01 TW
009218-05; www.flc.nih.gov). PJ is supported by a Wellcome Trust,
Department of Biotechnology India Alliance clinical and public health
intermediate career fellowship (www.wellcome.ac.uk). The views expressed
in this article are those of the authors and do not necessarily
represent the views of the National Heart, Lung, and Blood Institute,
National Institutes of Health, or the U.S. Department of Health and
Human Services. The funders had no role in study design, data collection
and analysis, decision to publish, or preparation of the manuscript.
NR 68
TC 3
Z9 3
U1 6
U2 9
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUN 14
PY 2016
VL 11
IS 6
AR e0157036
DI 10.1371/journal.pone.0157036
PG 28
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DO5KO
UT WOS:000377822200025
PM 27299563
ER
PT J
AU Moscicki, AB
Yao, TJ
Ryder, MI
Russell, JS
Dominy, SS
Patel, K
McKenna, M
Van Dyke, RB
Seage, GR
Hazra, R
Shiboski
AF Moscicki, Anna-Barbara
Yao, Tzy-Jyun
Ryder, Mark I.
Russell, Jonathan S.
Dominy, Stephen S.
Patel, Kunjal
McKenna, Matt
Van Dyke, Russell B.
Seage, George R., III
Hazra, Rohan
Shiboski
TI The Burden of Oral Disease among Perinatally HIV-Infected and
HIV-Exposed Uninfected Youth
SO PLOS ONE
LA English
DT Article
ID EARLY ENAMEL CARIES; DENTAL-CARIES; ANTIRETROVIRAL TREATMENT; US
CHILDREN; PREVALENCE; PREDICTORS; BACTERIA; THERAPY; LESIONS; HUMANS
AB Objective
To compare oral health parameters in perinatally HIV-infected (PHIV) and perinatally HIV-exposed but uninfected youth (PHEU).
Methods
In a cross-sectional substudy within the Pediatric HIV/AIDS Cohort Study, participants were examined for number of decayed teeth (DT), Decayed, Missing, and Filled Teeth (DMFT), oral mucosal disease, and periodontal disease (PD). Covariates for oral health parameters were examined using zero-inflated negative binomial regression and ordinal logistic regression models.
Results
Eleven sites enrolled 209 PHIV and 126 PHEU. Higher DT scores were observed in participants who were PHIV [ Adjusted Mean Ratio (aMR) = 1.7 (95% CI 1.2-2.5)], female [ aMR = 1.4 (1.0-1.9)], had no source of regular dental care [aMR = 2.3 (1.5-3.4)], and had a high frequency of meals/snacks [>= 5 /day vs 0-3, aMR = 1.9 (1.1-3.1)] and juice/soda [>= 5 /day vs 0-3, aMR = 1.6 (1.1-2.4)]. Higher DMFT scores were observed in participants who were older [>= 19, aMR = 1.9 (1.2-2.9)], had biological parent as caregiver [ aMR = 1.2 (1.0-1.3)], had a high frequency of juice/soda [>= 5 /day vs 0-3, aMR = 1.4 (1.1-1.7)] and a low salivaflow rate [mL/min, aMR = 0.8 per unit higher (0.6-1.0)]. Eighty percent had PD; no differences were seen by HIV status using the patient-based classifications of health, gingivitis or mild, moderate, or severe periodontitis. No associations were observed of CD4 count and viral load with oral health outcomes after adjustment.
Conclusions
Oral health was poor in PHIV and PHEU youth. This was dismaying since most HIV infected children in the U.S. are carefully followed at medical health care clinics. This data underscore the need for regular dental care. As PHIV youth were at higher risk for cavities, it will be important to better understand this relationship in order to develop targeted interventions.
C1 [Moscicki, Anna-Barbara] Univ Calif Los Angeles, Dept Pediat, Div Adolescent Med, Los Angeles, CA 90024 USA.
[Yao, Tzy-Jyun; Russell, Jonathan S.; McKenna, Matt] Harvard Univ, TH Chan Sch Publ Hlth, Ctr Biostat AIDS Res, Boston, MA 02115 USA.
[Ryder, Mark I.; Shiboski] Univ Calif San Francisco, Sch Dent, Dept Orofacial Sci, San Francisco, CA USA.
[Dominy, Stephen S.] Univ Calif San Francisco, Sch Med, Dept Psychiat, San Francisco, CA 94143 USA.
[Patel, Kunjal] Harvard Univ, TH Chan Sch Publ Hlth, Dept Epidemiol, Ctr Biostat AIDS Res, Boston, MA 02115 USA.
[Van Dyke, Russell B.] Tulane Univ, Sch Med, Dept Pediat, New Orleans, LA 70112 USA.
[Seage, George R., III] Harvard Univ, TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.
[Hazra, Rohan] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Maternal & Pediat Infect Dis Branch, NIH, Bethesda, MD USA.
RP Moscicki, AB (reprint author), Univ Calif Los Angeles, Dept Pediat, Div Adolescent Med, Los Angeles, CA 90024 USA.
EM amoscicki@mednet.ucla.edu
FU National Institute of Dental and Craniofacial Research; Eunice Kennedy
Shriver National Institute of Child Health and Human Development;
National Institute on Drug Abuse; National Institute of Allergy and
Infectious Diseases; Office of AIDS Research; National Institute of
Mental Health; National Institute of Neurological Disorders and Stroke;
National Institute on Deafness and Other Communication Disorders;
National Heart Lung and Blood Institute; National Institute on Alcohol
Abuse and Alcoholism; Harvard T. H. Chan School of Public Health
[HD052102, 3 U01 HD052102-05S1, 3 U01 HD052102-06S3]; Tulane University
School of Medicine [HD052104, 3U01 HD052104-06S1]
FX This study was supported by the National Institute of Dental and
Craniofacial Research and Eunice Kennedy Shriver National Institute of
Child Health and Human Development with cofunding from the National
Institute on Drug Abuse, the National Institute of Allergy and
Infectious Diseases, the Office of AIDS Research, the National Institute
of Mental Health, the National Institute of Neurological Disorders and
Stroke, the National Institute on Deafness and Other Communication
Disorders, the National Heart Lung and Blood Institute, and the National
Institute on Alcohol Abuse and Alcoholism, through cooperative
agreements with the Harvard T. H. Chan School of Public Health
(HD052102, 3 U01 HD052102-05S1, and 3 U01 HD052102-06S3) (PI: George
Seage; Project Director: Julie Alperen) and the Tulane University School
of Medicine (HD052104, 3U01 HD052104-06S1) (PI: Russell Van Dyke; Co-PI:
Kenneth Rich; Project Director: Patrick Davis). Data management services
were provided by Frontier Science and Technology Research Foundation
(PI: Suzanne Siminski), and regulatory services and logistical support
were provided by Westat, Inc (PI: Julie Davidson). The funders NICHD
have a significant role in study design, data collection, decision to
publish and preparation of manuscript. This does not alter the authors'
adherence to PLOS ONE policies on sharing data and materials. Westat,
Inc. provided regulatory services, protocol development support and
logistical support but had no additional role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 38
TC 2
Z9 2
U1 1
U2 3
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUN 14
PY 2016
VL 11
IS 6
AR e0156459
DI 10.1371/journal.pone.0156459
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DO5KO
UT WOS:000377822200008
PM 27299992
ER
PT J
AU Soto, C
Ofek, G
Joyce, MG
Zhang, BS
Mckee, K
Longo, NS
Yang, YP
Huang, JH
Parks, R
Eudailey, J
Lloyd, KE
Alam, SM
Haynes, BF
Mullikin, JC
Connors, M
Mascola, JR
Shapiro, L
Kwong, PD
AF Soto, Cinque
Ofek, Gilad
Joyce, M. Gordon
Zhang, Baoshan
Mckee, Krisha
Longo, Nancy S.
Yang, Yongping
Huang, Jinghe
Parks, Robert
Eudailey, Joshua
Lloyd, Krissey E.
Alam, S. Munir
Haynes, Barton F.
Mullikin, James C.
Connors, Mark
Mascola, John R.
Shapiro, Lawrence
Kwong, Peter D.
CA NISC Comparative Sequencing
TI Developmental Pathway of the MPER-Directed HIV-1-Neutralizing Antibody
10E8
SO PLOS ONE
LA English
DT Article
ID IMMUNODEFICIENCY-VIRUS TYPE-1; BROADLY NEUTRALIZING ANTIBODIES; POTENT
NEUTRALIZATION; HIV-1 NEUTRALIZATION; 2F5-LIKE ANTIBODIES; IMMUNOGEN
DESIGN; STRUCTURAL BASIS; GP41; EPITOPE; AUTOREACTIVITY
AB Antibody 10E8 targets the membrane-proximal external region (MPER) of HIV-1 gp41, neutralizes >97% of HIV-1 isolates, and lacks the auto-reactivity often associated with MPER-directed antibodies. The developmental pathway of 10E8 might therefore serve as a promising template for vaccine design, but samples from time-of-infection-often used to infer the B cell record-are unavailable. In this study, we used crystallography, next-generation sequencing (NGS), and functional assessments to infer the 10E8 developmental pathway from a single time point. Mutational analysis indicated somatic hypermutation of the 2nd-heavy chain-complementarity determining region (CDR H2) to be critical for neutralization, and structures of 10E8 variants with V-gene regions reverted to genomic origin for heavy- nd-light chains or heavy chain-only showed structural differences > 2 angstrom relative to mature 10E8 in the CDR H2 and H3. To understand these developmental changes, we used bioinformatic sieving, maximum likelihood, and parsimony analyses of immunoglobulin transcripts to identify 10E8-lineage members, to infer the 10E8-unmutated common ancestor (UCA), and to calculate 10E8-developmental intermediates. We were assisted in this analysis by the preservation of a critical D-gene segment, which was unmutated in most 10E8-lineage sequences. UCA and early intermediates weakly bound a 26-residue-MPER peptide, whereas HIV-1 neutralization and epitope recognition in liposomes were only observed with late intermediates. Antibody 10E8 thus develops from a UCA with weak MPER affinity and substantial differences in CDR H2 and H3 from the mature 10E8; only after extensive somatic hypermutation do 10E8-lineage members gain recognition in the context of membrane and HIV-1 neutralization.
C1 [Soto, Cinque; Ofek, Gilad; Joyce, M. Gordon; Zhang, Baoshan; Mckee, Krisha; Longo, Nancy S.; Yang, Yongping; Mascola, John R.; Shapiro, Lawrence; Kwong, Peter D.] NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Huang, Jinghe; Connors, Mark] NIAID, Immunoregulat Lab, NIH, Bldg 10, Bethesda, MD 20892 USA.
[Parks, Robert; Eudailey, Joshua; Lloyd, Krissey E.; Alam, S. Munir; Haynes, Barton F.] Duke Univ, Med Ctr, Duke Human Vaccine Inst, Durham, NC USA.
[Mullikin, James C.; NISC Comparative Sequencing] NHGRI, NIH Intramural Sequencing Ctr, NIH, Bethesda, MD 20892 USA.
[Shapiro, Lawrence] Columbia Univ, Dept Biochem & Mol Biophys, New York, NY USA.
RP Mascola, JR; Shapiro, L; Kwong, PD (reprint author), NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.; Shapiro, L (reprint author), Columbia Univ, Dept Biochem & Mol Biophys, New York, NY USA.
EM jmascola@nih.gov; shapiro@convex.hhmi.columbia.edu; pdkwong@nih.gov
FU Intramural Research Program of the Vaccine Research Center, National
Institute of Allergy and Infectious Diseases, National Institutes of
Health; National Human Genome Research Institute, National Institutes of
Health; Center for HIV/AIDS Vaccine Immunology-Immunogen Design grant
from the Division of AIDS National Institutes of Infectious Disease, NIH
[UM1 AI100645]
FX Support for this work was provided by the Intramural Research Program of
the Vaccine Research Center, National Institute of Allergy and
Infectious Diseases and the National Human Genome Research Institute,
National Institutes of Health, and by the Center for HIV/AIDS Vaccine
Immunology-Immunogen Design grant UM1 AI100645 to BFH from the Division
of AIDS National Institutes of Infectious Disease, NIH. The funders had
no role in study design, data collection and analysis, decision to
publish, or preparation of the manuscript.
NR 38
TC 6
Z9 6
U1 1
U2 3
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUN 14
PY 2016
VL 11
IS 6
AR e0157409
DI 10.1371/journal.pone.0157409
PG 21
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DO5KO
UT WOS:000377822200046
PM 27299673
ER
PT J
AU Zainabadi, K
AF Zainabadi, Kayvan
TI Malaria Parasite CLAG3, a Protein Linked to Nutrient Channels,
Participates in High Molecular Weight Membrane-Associated Complexes in
the Infected Erythrocyte
SO PLOS ONE
LA English
DT Article
ID RED-BLOOD-CELLS; SURFACE ANION CHANNEL; PLASMODIUM-FALCIPARUM; HOST
ERYTHROCYTE; PERMEATION PATHWAYS; MULTIGENE FAMILY; RHOPH COMPLEX;
RESISTANCE; PERMEABILITY; COMPONENT
AB Malaria infected erythrocytes show increased permeability to a number of solutes important for parasite growth as mediated by the Plasmodial Surface Anion Channel (PSAC). The P. falciparum clag3 genes have recently been identified as key determinants of PSAC, though exactly how they contribute to channel function and whether additional host/ parasite proteins are required remain unknown. To begin to answer these questions, I have taken a biochemical approach. Here I have used an epitope-tagged CLAG3 parasite to perform coimmunoprecipitation experiments using membrane fractions of infected erythrocytes. Native PAGE and mass spectrometry studies reveal that CLAG3 participate in at least three different high molecular weight complexes: a similar to 720kDa complex consisting of CLAG3, RHOPH2 and RHOPH3; a similar to 620kDa complex consisting of CLAG3 and RHOPH2; and a similar to 480kDa complex composed solely of CLAG3. Importantly, these complexes can be found throughout the parasite lifecycle but are absent in untransfected controls. Extracellular biotin labeling and protease susceptibility studies localize the 480kDa complex to the erythrocyte membrane. This complex, likely composed of a homo-oligomer of 160kDa CLAG3, may represent a functional subunit, possibly the pore, of PSAC.
C1 [Zainabadi, Kayvan] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD USA.
[Zainabadi, Kayvan] Univ Maryland, Sch Med, Inst Global Hlth, Div Malaria Res, Baltimore, MD 21201 USA.
RP Zainabadi, K (reprint author), NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD USA.; Zainabadi, K (reprint author), Univ Maryland, Sch Med, Inst Global Hlth, Div Malaria Res, Baltimore, MD 21201 USA.
EM kzainabadi@medicine.umaryland.edu
FU Malaria Infection Biology Research Fellowship (NIAID); Intramural
Research Program of NIAID, National Institutes of Health
FX This research was supported by a Malaria Infection Biology Research
Fellowship (NIAID) and by the Intramural Research Program of NIAID,
National Institutes of Health.; I would like to thank Susan Pierce for
her encouragement, Louis Miller and Tom Wellems for their support and
critical reading of the manuscript, Sanjay Desai for helpful discussions
and feedback on experiments, and the Research Technologies Branch of the
National Institutes of Allergy and Infectious Diseases (NIAD),
particularly Renee Olano, for their help with mass spectrometry
experiments. This research was supported by a Malaria Infection Biology
Research Fellowship (NIAID) and by the Intramural Research Program of
NIAID, National Institutes of Health.
NR 35
TC 1
Z9 1
U1 0
U2 1
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUN 14
PY 2016
VL 11
IS 6
AR e0157390
DI 10.1371/journal.pone.0157390
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DO5KO
UT WOS:000377822200045
PM 27299521
ER
PT J
AU Grace, PM
Strand, KA
Galer, EL
Urban, DJ
Wang, XH
Baratta, MV
Fabisiak, TJ
Anderson, ND
Cheng, KJ
Greene, LI
Berkelhammer, D
Zhang, YN
Ellis, AL
Yin, HH
Campeau, S
Rice, KC
Roth, BL
Maier, SF
Watkins, LR
AF Grace, Peter M.
Strand, Keith A.
Galer, Erika L.
Urban, Daniel J.
Wang, Xiaohui
Baratta, Michael V.
Fabisiak, Timothy J.
Anderson, Nathan D.
Cheng, Kejun
Greene, Lisa I.
Berkelhammer, Debra
Zhang, Yingning
Ellis, Amanda L.
Yin, Hang Hubert
Campeau, Serge
Rice, Kenner C.
Roth, Bryan L.
Maier, Steven F.
Watkins, Linda R.
TI Morphine paradoxically prolongs neuropathic pain in rats by amplifying
spinal NLRP3 inflammasome activation
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE TLR4; P2X7R; danger signals; DAMP; opioid-induced hyperalgesia
ID OPIOID-INDUCED HYPERALGESIA; HIV-1 ENVELOPE GLYCOPROTEIN;
PROINFLAMMATORY CYTOKINES; PERIPHERAL INFECTION; POSTOPERATIVE PAIN;
IMMUNE ACTIVATION; P2X(7) RECEPTORS; CONTROLLED-TRIAL; UNITED-STATES;
MURINE MODEL
AB Opioid use for pain management has dramatically increased, with little assessment of potential pathophysiological consequences for the primary pain condition. Here, a short course of morphine, starting 10 d after injury in male rats, paradoxically and remarkably doubled the duration of chronic constriction injury (CCI)-allodynia, months after morphine ceased. No such effect of opioids on neuropathic pain has previously been reported. Using pharmacologic and genetic approaches, we discovered that the initiation and maintenance of this multimonth prolongation of neuropathic pain was mediated by a previously unidentified mechanism for spinal cord and pain-namely, morphine-induced spinal NOD-like receptor protein 3 (NLRP3) inflammasomes and associated release of interleukin-1 beta (IL-1 beta). As spinal dorsal horn microglia expressed this signaling platform, these cells were selectively inhibited in vivo after transfection with a novel Designer Receptor Exclusively Activated by Designer Drugs (DREADD). Multiday treatment with the DREADD-specific ligand clozapine-N-oxide prevented and enduringly reversed morphine-induced persistent sensitization for weeks to months after cessation of clozapine-N-oxide. These data demonstrate both the critical importance of microglia and that maintenance of chronic pain created by early exposure to opioids can be disrupted, resetting pain to normal. These data also provide strong support for the recent "two-hit hypothesis" of microglial priming, leading to exaggerated reactivity after the second challenge, documented here in the context of nerve injury followed by morphine. This study predicts that prolonged pain is an unrealized and clinically concerning consequence of the abundant use of opioids in chronic pain.
C1 [Grace, Peter M.; Strand, Keith A.; Galer, Erika L.; Wang, Xiaohui; Baratta, Michael V.; Fabisiak, Timothy J.; Anderson, Nathan D.; Greene, Lisa I.; Berkelhammer, Debra; Zhang, Yingning; Ellis, Amanda L.; Campeau, Serge; Maier, Steven F.; Watkins, Linda R.] Univ Colorado, Dept Psychol & Neurosci, Boulder, CO 80309 USA.
[Grace, Peter M.; Strand, Keith A.; Galer, Erika L.; Wang, Xiaohui; Baratta, Michael V.; Fabisiak, Timothy J.; Anderson, Nathan D.; Greene, Lisa I.; Berkelhammer, Debra; Zhang, Yingning; Ellis, Amanda L.; Yin, Hang Hubert; Campeau, Serge; Maier, Steven F.; Watkins, Linda R.] Univ Colorado, Ctr Neurosci, Boulder, CO 80309 USA.
[Grace, Peter M.] Univ Adelaide, Sch Med, Discipline Pharmacol, Adelaide, SA 5005, Australia.
[Urban, Daniel J.; Roth, Bryan L.] Univ N Carolina, Dept Pharmacol, Chapel Hill, NC 27599 USA.
[Wang, Xiaohui] Chinese Acad Sci, Changchun Inst Appl Chem, Chem Biol Lab, Changchun 130022, Jilin, Peoples R China.
[Wang, Xiaohui; Yin, Hang Hubert] Univ Colorado, Dept Chem & Biochem, Boulder, CO 80309 USA.
[Wang, Xiaohui; Yin, Hang Hubert] Univ Colorado, BioFrontiers Inst, Boulder, CO 80309 USA.
[Cheng, Kejun; Rice, Kenner C.] NIAAA, Chem Biol Res Branch, Bethesda, MD 20892 USA.
[Yin, Hang Hubert] Tsinghua Univ, Dept Chem, Ctr Basic Mol Sci, Beijing 100082, Peoples R China.
RP Grace, PM (reprint author), Univ Colorado, Dept Psychol & Neurosci, Boulder, CO 80309 USA.; Grace, PM (reprint author), Univ Colorado, Ctr Neurosci, Boulder, CO 80309 USA.; Grace, PM (reprint author), Univ Adelaide, Sch Med, Discipline Pharmacol, Adelaide, SA 5005, Australia.
EM peter.grace@colorado.edu
OI Grace, Peter/0000-0002-8999-1220
FU American Pain Society Future Leaders in Pain Research Grants Program;
National Health and Medical Research Council CJ Martin Fellowship
[1054091]; American Australian Association Sir Keith Murdoch Fellowship;
National Natural Science Foundation of China [21543013]; Natural Science
Foundation of Jilin Province [20160101211JC]; NIH [DE021966, DA023132,
DA017204, U01MH105892, GM101279]; NIH Intramural Research Programs of
the National Institute on Drug Abuse; National Institute of Alcohol
Abuse and Alcoholism
FX This work was supported by the American Pain Society Future Leaders in
Pain Research Grants Program (P.M.G.); National Health and Medical
Research Council CJ Martin Fellowship ID 1054091 (to P.M.G.); American
Australian Association Sir Keith Murdoch Fellowship (P.M.G.); National
Natural Science Foundation of China Grant 21543013 (to X.W.); Natural
Science Foundation of Jilin Province Grant 20160101211JC (to X.W.); and
NIH Grants DE021966, DA023132 (to L.R.W.), DA017204 (to D.J.U. and
B.L.R.), U01MH105892 (to B.L.R.), and GM101279 (to H.H.Y.). The work of
the Chemical Biology Research Branch was supported by the NIH Intramural
Research Programs of the National Institute on Drug Abuse and the
National Institute of Alcohol Abuse and Alcoholism.
NR 85
TC 11
Z9 11
U1 7
U2 13
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD JUN 14
PY 2016
VL 113
IS 24
BP E3441
EP E3450
DI 10.1073/pnas.1602070113
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DO7FW
UT WOS:000377948800018
PM 27247388
ER
PT J
AU Li, H
Wang, SY
Kong, R
Ding, WG
Lee, FH
Parker, Z
Kim, E
Learn, GH
Hahn, P
Policicchio, B
Brocca-Cofano, E
Deleage, C
Hao, XP
Chuang, GY
Gorman, J
Gardner, M
Lewis, MG
Hatziioannou, T
Santra, S
Apetrei, C
Pandrea, I
Alam, SM
Liao, HX
Shen, XY
Tomaras, GD
Farzan, M
Chertova, E
Keele, BF
Estes, JD
Lifson, JD
Doms, RW
Montefiori, DC
Haynes, BF
Sodroski, JG
Kwong, PD
Hahn, BH
Shaw, GM
AF Li, Hui
Wang, Shuyi
Kong, Rui
Ding, Wenge
Lee, Fang-Hua
Parker, Zahra
Kim, Eunlim
Learn, Gerald H.
Hahn, Paul
Policicchio, Ben
Brocca-Cofano, Egidio
Deleage, Claire
Hao, Xingpei
Chuang, Gwo-Yu
Gorman, Jason
Gardner, Matthew
Lewis, Mark G.
Hatziioannou, Theodora
Santra, Sampa
Apetrei, Cristian
Pandrea, Ivona
Alam, S. Munir
Liao, Hua-Xin
Shen, Xiaoying
Tomaras, Georgia D.
Farzan, Michael
Chertova, Elena
Keele, Brandon F.
Estes, Jacob D.
Lifson, Jeffrey D.
Doms, Robert W.
Montefiori, David C.
Haynes, Barton F.
Sodroski, Joseph G.
Kwong, Peter D.
Hahn, Beatrice H.
Shaw, George M.
TI Envelope residue 375 substitutions in simian-human immunodeficiency
viruses enhance CD4 binding and replication in rhesus macaques
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE HIV/AIDS; SHIV; CD4; HIV-1 envelope
ID BROADLY NEUTRALIZING ANTIBODIES; GP120 INNER DOMAIN; INFECTIOUS
MOLECULAR CLONES; HIV-1 ENVELOPE; IN-VIVO; CONFORMATIONAL TRANSITIONS;
QUATERNARY INTERACTIONS; CD4-BOUND CONFORMATION; SUBOPTIMAL NUCLEOTIDES;
CHALLENGE STOCKS
AB Most simian-human immunodeficiency viruses (SHIVs) bearing envelope (Env) glycoproteins from primary HIV-1 strains fail to infect rhesus macaques (RMs). We hypothesized that inefficient Env binding to rhesus CD4 (rhCD4) limits virus entry and replication and could be enhanced by substituting naturally occurring simian immunodeficiency virus Env residues at position 375, which resides at a critical location in the CD4-binding pocket and is under strong positive evolutionary pressure across the broad spectrum of primate lentiviruses. SHIVs containing primary or transmitted/founder HIV-1 subtype A, B, C, or D Envs with genotypic variants at residue 375 were constructed and analyzed in vitro and in vivo. Bulky hydrophobic or basic amino acids substituted for serine-375 enhanced Env affinity for rhCD4, virus entry into cells bearing rhCD4, and virus replication in primary rhCD4 T cells without appreciably affecting antigenicity or antibody-mediated neutralization sensitivity. Twenty-four RMs inoculated with subtype A, B, C, or D SHIVs all became productively infected with different Env375 variants-S, M, Y, H, W, or F-that were differentially selected in different Env backbones. Notably, SHIVs replicated persistently at titers comparable to HIV-1 in humans and elicited autologous neutralizing antibody responses typical of HIV-1. Seven animals succumbed to AIDS. These findings identify Env-rhCD4 binding as a critical determinant for productive SHIV infection in RMs and validate a novel and generalizable strategy for constructing SHIVs with Env glycoproteins of interest, including those that in humans elicit broadly neutralizing antibodies or bind particular Ig germ-line B-cell receptors.
C1 [Li, Hui; Wang, Shuyi; Kong, Rui; Ding, Wenge; Lee, Fang-Hua; Parker, Zahra; Kim, Eunlim; Learn, Gerald H.; Hahn, Paul; Hahn, Beatrice H.; Shaw, George M.] Univ Penn, Dept Med, Philadelphia, PA 19104 USA.
[Policicchio, Ben; Brocca-Cofano, Egidio; Apetrei, Cristian; Pandrea, Ivona] Univ Pittsburgh, Ctr Vaccine Res, Pittsburgh, PA 15261 USA.
[Deleage, Claire; Hao, Xingpei; Chertova, Elena; Keele, Brandon F.; Estes, Jacob D.; Lifson, Jeffrey D.; Kwong, Peter D.] Frederick Natl Lab, Leidos Biomed Res Inc, AIDS & Canc Virus Program, Frederick, MD 21702 USA.
[Chuang, Gwo-Yu; Gorman, Jason] NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Gardner, Matthew; Farzan, Michael] Scripps Res Inst, Dept Infect Dis, Jupiter, FL 33458 USA.
[Lewis, Mark G.] Bioqual Inc, Rockville, MD 20852 USA.
[Hatziioannou, Theodora] Rockefeller Univ, Aaron Diamond AIDS Res Ctr, New York, NY 10016 USA.
[Santra, Sampa] Beth Israel Deaconess Med Ctr, Ctr Virol & Vaccine Res, Boston, MA 02215 USA.
[Alam, S. Munir; Liao, Hua-Xin; Shen, Xiaoying; Tomaras, Georgia D.; Montefiori, David C.; Haynes, Barton F.] Duke Univ, Dept Med, Durham, NC 27710 USA.
[Doms, Robert W.] Childrens Hosp Philadelphia, Dept Pathol, Philadelphia, PA 19104 USA.
[Sodroski, Joseph G.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & Virol, Boston, MA 02215 USA.
RP Hahn, BH; Shaw, GM (reprint author), Univ Penn, Dept Med, Philadelphia, PA 19104 USA.
EM bhahn@upenn.edu; shawg@upenn.edu
FU Bill & Melinda Gates Foundation [OPP37874, OPP1145046]; NIH Grants
[AI100645, AI088564, AI094604, AI087383, AI078788, AI045008,
HHSN261200800001E]
FX We thank C. Xu, T. He, T. Dunsmore, G. H. Richter, K. Raehtz, J. Roser,
R. Fast, K. Oswald, R. Shoemaker, J. Bess, and A. Meyer for technical
assistance. This project was funded in part by Bill & Melinda Gates
Foundation Grants OPP37874 and OPP1145046; and NIH Grants AI100645,
AI088564, AI094604, AI087383, AI078788, AI045008, and HHSN261200800001E.
NR 117
TC 12
Z9 12
U1 1
U2 3
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD JUN 14
PY 2016
VL 113
IS 24
BP E3413
EP E3422
DI 10.1073/pnas.1606636113
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DO7FW
UT WOS:000377948800015
PM 27247400
ER
PT J
AU Burnham, P
Kim, MS
Agbor-Enoh, S
Luikart, H
Valantine, HA
Khush, KK
De Vlaminck, I
AF Burnham, Philip
Kim, Min Seong
Agbor-Enoh, Sean
Luikart, Helen
Valantine, Hannah A.
Khush, Kiran K.
De Vlaminck, Iwijn
TI Single-stranded DNA library preparation uncovers the origin and
diversity of ultrashort cell-free DNA in plasma
SO SCIENTIFIC REPORTS
LA English
DT Article
ID NONINVASIVE DIAGNOSIS; TRANSPLANT RECIPIENTS; READ ALIGNMENT; SEQUENCE;
REJECTION; INJURY; PCR
AB Circulating cell-free DNA (cfDNA) is emerging as a powerful monitoring tool in cancer, pregnancy and organ transplantation. Nucleosomal DNA, the predominant form of plasma cfDNA, can be adapted for sequencing via ligation of double-stranded DNA (dsDNA) adapters. dsDNA library preparations, however, are insensitive to ultrashort, degraded cfDNA. Drawing inspiration from advances in paleogenomics, we have applied a single-stranded DNA (ssDNA) library preparation method to sequencing of cfDNA in the plasma of lung transplant recipients (40 samples, six patients). We found that ssDNA library preparation yields a greater portion of sub-100 bp nuclear genomic cfDNA (p << 10(-5), Mann-Whitney U Test), and an increased relative abundance of mitochondrial (10.7x, p << 10(-5)) and microbial cfDNA (71.3x, p << 10(-5)). The higher yield of microbial sequences from this method increases the sensitivity of cfDNA-based monitoring for infections following transplantation. We detail the fragmentation pattern of mitochondrial, nuclear genomic and microbial cfDNA over a broad fragment length range. We report the observation of donor-specific mitochondrial cfDNA in the circulation of lung transplant recipients. A ssDNA library preparation method provides a more informative window into understudied forms of cfDNA, including mitochondrial and microbial derived cfDNA and short nuclear genomic cfDNA, while retaining information provided by standard dsDNA library preparation methods.
C1 [Burnham, Philip; Kim, Min Seong; De Vlaminck, Iwijn] Cornell Univ, Meinig Sch Biomed Engn, Ithaca, NY 14853 USA.
[Agbor-Enoh, Sean; Valantine, Hannah A.] NIH, Bldg 10, Bethesda, MD 20892 USA.
[Luikart, Helen; Khush, Kiran K.] Stanford Univ, Sch Med, Div Cardiovasc Med, Stanford, CA 94305 USA.
RP De Vlaminck, I (reprint author), Cornell Univ, Meinig Sch Biomed Engn, Ithaca, NY 14853 USA.
EM id93@cornell.edu
OI De Vlaminck, Iwijn/0000-0001-6085-7311
FU Noyce Foundation; National Science Foundation GRFP [DGE-1144153]
FX We thank Fanny Chen and Peter Schweitzer for assistance with library
preparation and sequencing assays. We thank Erin Berthelsen, Robert
Goggs, Elizabeth Wilcox and Rory James Todhunter (Cornell University
College of Veterinary Medicine), for providing animal blood samples for
assay testing and development. This work is supported by the Noyce
Foundation (IDV), and the National Science Foundation GRFP (PB,
DGE-1144153).
NR 41
TC 2
Z9 2
U1 4
U2 10
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2045-2322
J9 SCI REP-UK
JI Sci Rep
PD JUN 14
PY 2016
VL 6
AR 27859
DI 10.1038/srep27859
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DO5MR
UT WOS:000377827700001
PM 27297799
ER
PT J
AU Li, M
Dai, YX
Zhu, YJ
Fu, CL
Tan, VY
Wang, YA
Wang, X
Hong, XF
Liu, Q
Li, TM
Qin, JX
Ma, XW
Fang, JY
Otto, M
AF Li, Min
Dai, Yingxin
Zhu, Yuanjun
Fu, Chih-Lung
Tan, Vee Y.
Wang, Yanan
Wang, Xing
Hong, Xufen
Liu, Qian
Li, Tianming
Qin, Juanxiu
Ma, Xiaowei
Fang, Jingyuan
Otto, Michael
TI Virulence determinants associated with the Asian community-associated
methicillin-resistant Staphylococcus aureus lineage ST59
SO SCIENTIFIC REPORTS
LA English
DT Article
ID PHENOL-SOLUBLE MODULINS; MONOCLONAL-ANTIBODY; GENE-EXPRESSION;
ALPHA-TOXIN; INFECTIONS; EVOLUTION; USA300; TISSUE; AGR; STRAINS
AB Understanding virulence is vital for the development of novel therapeutics to target infections with community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA), which cause an ongoing epidemic in the United States and are on a global rise. However, what defines virulence particularly of global CA-MRSA lineages is poorly understood. Threatening a vast population, the predominant Asian CA-MRSA lineage ST59 is of major epidemiological importance. However, there have been no molecular analyses using defined virulence gene deletion mutants in that lineage as of yet. Here, we compared virulence in skin, lung, and blood infection models of ST59 CA-MRSA isolates with geographically matched hospital-associated MRSA isolates. We selected a representative ST59 CA-MRSA isolate based on toxin expression and virulence characteristics, and produced isogenic gene deletion mutants of important CA-MRSA virulence determinants (alpha-toxin, PSM alpha, Agr) in that isolate for in-vitro and in-vivo analyses. Our results demonstrate strongly enhanced virulence of ST59 CA-MRSA over hospital-associated lineages, supporting the notion that enhanced virulence is characteristic for CA-MRSA. Furthermore, they show strong and significant contribution of Agr, alpha-toxin, and PSM alpha to pathogenesis of ST59 CA-MRSA skin, lung, and blood infection, emphasizing the value of drug development efforts targeted toward those virulence determinants.
C1 [Li, Min; Dai, Yingxin; Zhu, Yuanjun; Wang, Yanan; Hong, Xufen; Liu, Qian; Li, Tianming; Qin, Juanxiu; Ma, Xiaowei] Shanghai Jiao Tong Univ, Sch Med, Renji Hosp, Dept Lab Med, Shanghai, Peoples R China.
[Zhu, Yuanjun; Fu, Chih-Lung; Tan, Vee Y.; Otto, Michael] NIAID, Pathogen Mol Genet Sect, Bacteriol Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Wang, Xing] Shanghai Jiao Tong Univ, Sch Med, Shanghai Childrens Med Ctr, Dept Lab Med, Shanghai, Peoples R China.
[Fang, Jingyuan] Shanghai Jiao Tong Univ, Shanghai Inst Digest Dis, Sch Med, Dept Gastroenterol & Hepatol,Renji Hosp, Shanghai, Peoples R China.
RP Li, M (reprint author), Shanghai Jiao Tong Univ, Sch Med, Renji Hosp, Dept Lab Med, Shanghai, Peoples R China.; Otto, M (reprint author), NIAID, Pathogen Mol Genet Sect, Bacteriol Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM ruth_limin@126.com; motto@niaid.nih.gov
FU Intramural Research Program of NIAID at NIH [ZIA AI000904]; National
Natural Science Foundation of China [81322025, 81371875]; Shanghai
Shuguang Talent Project [12SG03]; Shanghai Committee of Science and
Technology, China [14140901000, 15411960500]; Foundation for Innovative
Research Groups of the National Natural Science Foundation of China
[81421001]
FX The authors thank Binh An Diep for ST59 isolates from San Francisco.
This work was supported by the Intramural Research Program of NIAID at
NIH (grant ZIA AI000904 to M.O.), the National Natural Science
Foundation of China (grants 81322025 and 81371875, to M.L.), the
Shanghai Shuguang Talent Project (grant 12SG03, to M.L.), the Shanghai
Committee of Science and Technology, China (grants 14140901000,
15411960500, to M.L.) and the Foundation for Innovative Research Groups
of the National Natural Science Foundation of China (grant 81421001, to
M.L.).
NR 42
TC 1
Z9 1
U1 2
U2 6
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2045-2322
J9 SCI REP-UK
JI Sci Rep
PD JUN 14
PY 2016
VL 6
AR 27899
DI 10.1038/srep27899
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DO5MF
UT WOS:000377826500001
PM 27296890
ER
PT J
AU Biesecker, LG
AF Biesecker, Leslie G.
TI Long QT Syndrome and Potentially Pathogenic Genetic Variants
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Letter
ID EXOME
C1 [Biesecker, Leslie G.] NHGRI, NIH, Bldg 49 4A56, Bethesda, MD 20892 USA.
RP Biesecker, LG (reprint author), NHGRI, NIH, Bldg 49 4A56, Bethesda, MD 20892 USA.
EM lesb@mail.nih.gov
NR 3
TC 2
Z9 2
U1 1
U2 1
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 0098-7484
EI 1538-3598
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD JUN 14
PY 2016
VL 315
IS 22
BP 2467
EP 2467
DI 10.1001/jama.2016.2918
PG 1
WC Medicine, General & Internal
SC General & Internal Medicine
GA DO3CE
UT WOS:000377656900026
PM 27299623
ER
PT J
AU Weinsaft, JW
Devereux, RB
Preiss, LR
Feher, A
Roman, MJ
Basson, CT
Geevarghese, A
Ravekes, W
Dietz, HC
Holmes, K
Habashi, J
Pyeritz, RE
Bavaria, J
Milewski, K
LeMaire, SA
Morris, S
Milewicz, DM
Prakash, S
Maslen, C
Song, HK
Silberbach, GM
Shohet, RV
McDonnell, N
Hendershot, T
Eagle, KA
Asch, FM
AF Weinsaft, Jonathan W.
Devereux, Richard B.
Preiss, Liliana R.
Feher, Attila
Roman, Mary J.
Basson, Craig T.
Geevarghese, Alexi
Ravekes, William
Dietz, Harry C.
Holmes, Kathryn
Habashi, Jennifer
Pyeritz, Reed E.
Bavaria, Joseph
Milewski, Karianna
LeMaire, Scott A.
Morris, Shaine
Milewicz, Dianna M.
Prakash, Siddharth
Maslen, Cheryl
Song, Howard K.
Silberbach, G. Michael
Shohet, Ralph V.
McDonnell, Nazli
Hendershot, Tabitha
Eagle, Kim A.
Asch, Federico M.
CA GENTAC Registry Investigators
TI Aortic Dissection in Patients With Genetically Mediated Aneurysms
Incidence and Predictors in the GenTAC Registry
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Article
DE aortic aneurysm; aortic dissection; bicuspid aortic valve; Marfan
syndrome
ID MARFAN-SYNDROME; INTERNATIONAL REGISTRY; HEART-DISEASE; VALVE;
COMPLICATIONS; ELASTICITY; GUIDELINES; MANAGEMENT; DILATION; PATTERNS
AB BACKGROUND Aortic dissection (AoD) is a serious complication of thoracic aortic aneurysm (TAA). Relative risk for AoD in relation to TAA etiology, incidence, and pattern after prophylactic TAA surgery are poorly understood.
OBJECTIVES This study sought to determine the incidence, pattern, and relative risk for AoD among patients with genetically associated TAA.
METHODS The population included adult GenTAC participants without AoD at baseline. Standardized core laboratory tests classified TAA etiology and measured aortic size. Follow-up was performed for AoD.
RESULTS Bicuspid aortic valve (BAV) (39%) and Marfan syndrome (MFS) (22%) were the leading diagnoses in the studied GenTAC participants (n = 1,991). AoD occurred in 1.6% over 3.6 +/- 2.0 years; 61% of AoD occurred in patients with MFS. Cumulative AoD incidence was 6-fold higher among patients with MFS (4.5%) versus others (0.7%; p < 0.001). MFS event rates were similarly elevated versus those in patients with BAV (0.3%; p < 0.001). AoD originated in the distal arch or descending aorta in 71%; 52% of affected patients, including 68% with MFS, had previously undergone aortic grafting. In patients with proximal aortic surgery, distal aortic size (descending thoracic, abdominal aorta) was larger among patients with AoD versus those without AoD (both p < 0.05), whereas the ascending aorta size was similar. Conversely, in patients without previous surgery, aortic root size was greater in patients with subsequent AoD (p < 0.05), whereas distal aortic segments were of similar size. MFS (odds ratio: 7.42; 95% confidence interval: 3.43 to 16.82; p < 0.001) and maximal aortic size (1.86 per cm; 95% confidence interval: 1.26 to 2.67; p = 0.001) were independently associated with AoD. Only 4 of 31 (13%) patients with AoD had pre-dissection images that fulfilled size criteria for prophylactic TAA surgery at a subsequent AoD site.
CONCLUSIONS Among patients with genetically associated TAA, MFS augments risk for AoD even after TAA grafting. Although increased aortic size is a risk factor for subsequent AoD, events typically occur below established thresholds for prophylactic TAA repair. (C) 2016 by the American College of Cardiology Foundation.
C1 [Weinsaft, Jonathan W.; Devereux, Richard B.; Feher, Attila; Roman, Mary J.; Basson, Craig T.; Geevarghese, Alexi] Weill Cornell Med Coll, 525 East 68th St, New York, NY 10021 USA.
[Preiss, Liliana R.; Hendershot, Tabitha] RTI Int, Biostat & Epidemiol Div, Rockville, MD USA.
[Ravekes, William; Holmes, Kathryn; Habashi, Jennifer] Johns Hopkins Univ, Dept Pediat Cardiol, Baltimore, MD USA.
[Dietz, Harry C.] Johns Hopkins Univ, Inst Med Genet, Baltimore, MD USA.
[Pyeritz, Reed E.] Univ Penn, Div Med Genet, Philadelphia, PA 19104 USA.
[Bavaria, Joseph; Milewski, Karianna] Univ Penn, Div Cardiovasc Surg, Philadelphia, PA 19104 USA.
[LeMaire, Scott A.] Baylor Coll Med, Div Cardiothorac Surg, Houston, TX 77030 USA.
[LeMaire, Scott A.] Texas Heart Inst, Houston, TX 77025 USA.
[Morris, Shaine] Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA.
[Milewicz, Dianna M.; Prakash, Siddharth] Univ Texas Hlth Sci Ctr Houston, Div Med Genet, Houston, TX 77030 USA.
[Maslen, Cheryl] Oregon Hlth & Sci Univ, Heart Res Ctr, Portland, OR 97201 USA.
[Song, Howard K.] Oregon Hlth & Sci Univ, Div Cardiothorac Surg, Portland, OR 97201 USA.
[Silberbach, G. Michael] Oregon Hlth & Sci Univ, Dept Pediat Cardiol, Portland, OR 97201 USA.
[Shohet, Ralph V.] Queens Med Ctr, Div Cardiovasc Res, Honolulu, HI USA.
[McDonnell, Nazli] NIA, NIH, Baltimore, MD 21224 USA.
[Eagle, Kim A.] Univ Michigan Hlth Syst, Dept Cardiol, Ann Arbor, MI USA.
[Asch, Federico M.] Washington Hosp Ctr, MedStar Hlth Res Inst, Cardiovasc Core Lab, Washington, DC 20010 USA.
RP Weinsaft, JW (reprint author), Weill Cornell Med Coll, Dept Med, Greenberg Div Cardiol, 525 East 68th St, New York, NY 10021 USA.
EM jww2001@med.cornell.edu
FU National Heart, Lung, and Blood Institute; National Institute of
Arthritis, Musculoskeletal and Skin Diseases [HHSN268200648199C,
HHSN268201000048C]
FX GenTAC supported by National Heart, Lung, and Blood Institute and
National Institute of Arthritis, Musculoskeletal and Skin Diseases
(HHSN268200648199C, HHSN268201000048C). Dr. LeMaire is a member of the
Advisory Board for Baxter Healthcare; the clinical study principal
investigator for Vascutek Terumo and Baxter Healthcare; and a clinical
trial co-investigator for Medtronic, W.L. Gore & Associates, and
GlaxoSmithKline. All other authors have reported that they have no
relationships relevant to the contents of this paper to disclose.
NR 24
TC 3
Z9 3
U1 2
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
EI 1558-3597
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD JUN 14
PY 2016
VL 67
IS 23
BP 2744
EP 2754
DI 10.1016/j.jacc.2016.03.570
PG 11
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA DN7RF
UT WOS:000377274300007
PM 27282895
ER
PT J
AU Moreno, H
Morfini, G
Buitrago, L
Ujlaki, G
Choi, S
Yu, E
Moreira, JE
Avila, J
Brady, ST
Pant, H
Sugimori, M
Llinas, RR
AF Moreno, H.
Morfini, G.
Buitrago, L.
Ujlaki, G.
Choi, S.
Yu, E.
Moreira, J. E.
Avila, J.
Brady, S. T.
Pant, H.
Sugimori, M.
Llinas, R. R.
TI TAU PATHOLOGY-MEDIATED PRESYNAPTIC DYSFUNCTION
SO NEUROSCIENCE
LA English
DT Article
DE tauopathy; IP3 receptor; ryanodine receptor; phosphatase-activating
domain of tau; GSK3; Cdk5
ID INOSITOL 1,4,5-TRISPHOSPHATE RECEPTOR; DEPENDENT AXONAL-TRANSPORT;
AMYLOID PRECURSOR PROTEIN; EARLY ALZHEIMERS-DISEASE; SQUID GIANT
SYNAPSE; IN-VIVO; 2-AMINOETHOXYDIPHENYL BORATE; NEUROTRANSMITTER
RELEASE; FRONTOTEMPORAL DEMENTIA; INTRACELLULAR CA2+
AB Brain tauopathies are characterized by abnormal processing of tau protein. While somatodendritic tau mislocalization has attracted considerable attention in tauopathies, the role of tau pathology in axonal transport, connectivity and related dysfunctions remains obscure. We have previously shown using the squid giant synapse that presynaptic microinjection of recombinant human tau protein (htau42) results in failure of synaptic transmission. Here, we evaluated molecular mechanisms mediating this effect. Thus, the initial event, observed after htau42 presynaptic injection, was an increase in transmitter release. This event was mediated by calcium release from intracellular stores and was followed by a reduction in evoked transmitter release. The effect of htau42 on synaptic transmission was recapitulated by a peptide comprising the phosphatase-activating domain of tau, suggesting activation of phosphotransferases. Accordingly, findings indicated that htau42-mediated toxicity involves the activities of both GSK3 and Cdk5 kinases. (C) 2016 IBRO. Published by Elsevier Ltd. All rights reserved.
C1 [Moreno, H.; Buitrago, L.] Suny Downstate Med Ctr, Robert F Furchgott Ctr Neural & Behav Sci, Dept Neurol, Brooklyn, NY 11203 USA.
[Moreno, H.; Buitrago, L.] Suny Downstate Med Ctr, Robert F Furchgott Ctr Neural & Behav Sci, Dept Physiol Pharmacol, Brooklyn, NY 11203 USA.
[Moreno, H.; Morfini, G.; Buitrago, L.; Ujlaki, G.; Choi, S.; Yu, E.; Moreira, J. E.; Brady, S. T.; Pant, H.; Sugimori, M.; Llinas, R. R.] Marine Biol Lab, Woods Hole, MA 02543 USA.
[Morfini, G.; Brady, S. T.] Univ Illinois, Dept Anat & Cell Biol, Chicago, IL 60607 USA.
[Moreira, J. E.] Univ Sao Paulo, Riberao Preto Sch Med, Pathol & Forens Med, BR-14000000 Ribeirao Preto, SP, Brazil.
[Avila, J.] Univ Autonoma Madrid, Ctr Biol Mol Severo Ochoa, E-28049 Madrid, Spain.
[Pant, H.] NINDS, Lab Neurochem, Bethesda, MD 20824 USA.
[Choi, S.; Yu, E.; Sugimori, M.; Llinas, R. R.] NYU, Sch Med, Dept Physiol & Neurosci, New York, NY 10016 USA.
RP Moreno, H (reprint author), Marine Biol Lab, Woods Hole, MA 02543 USA.
EM Herman.Moreno@downstate.edu; Rodolfo.Llinas@nyumc.org
RI Avila, Jesus/I-2610-2015;
OI Avila, Jesus/0000-0002-6288-0571; Sugimori,
Mutsuyuki/0000-0002-2908-3167
FU NIH [AG027476, NS066942, NS23868, NS23320, NS41170, NS082730];
Alzheimer's Association; FAPESP (Science Foundation for the Sao Paulo
State, Brasil) [19011-0]
FX Supported by NIH AG027476 to H. Moreno; a donation from
ToyamaPharmaceuticals to RL and MS. NIH NS066942 (to GM), NS23868,
NS23320, NS41170, NS082730 (to STB) and a Zenith Award from the
Alzheimer's Association grants to STB and grant from FAPESP (Science
Foundation for the Sao Paulo State, Brasil; 19011-0) to JEM.
NR 42
TC 3
Z9 3
U1 2
U2 11
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0306-4522
EI 1873-7544
J9 NEUROSCIENCE
JI Neuroscience
PD JUN 14
PY 2016
VL 325
BP 30
EP 38
DI 10.1016/j.neuroscience.2016.03.044
PG 9
WC Neurosciences
SC Neurosciences & Neurology
GA DJ8ZK
UT WOS:000374503200004
PM 27012611
ER
PT J
AU Machiela, MJ
Zhou, WY
Karlins, E
Sampson, JN
Freedman, ND
Yang, Q
Hicks, B
Dagnall, C
Hautman, C
Jacobs, KB
Abnet, CC
Aldrich, MC
Amos, C
Amundadottir, LT
Arslan, AA
Beane-Freeman, LE
Berndt, SI
Black, A
Blot, WJ
Bock, CH
Bracci, PM
Brinton, LA
Bueno-De-Mesquita, HB
Burdett, L
Buring, JE
Butler, MA
Canzian, F
Carreon, T
Chaffee, KG
Chang, IS
Chatterjee, N
Chen, C
Chen, C
Chen, KX
Chung, CC
Cook, LS
Bou, MC
Cullen, M
Davis, FG
De Vivo, I
Ding, T
Doherty, J
Duell, EJ
Epstein, CG
Fan, JH
Figueroa, JD
Fraumeni, JF
Friedenreich, CM
Fuchs, CS
Gallinger, S
Gao, YT
Gapstur, SM
Garcia-Closas, M
Gaudet, MM
Gaziano, JM
Giles, GG
Gillanders, EM
Giovannucci, EL
Goldin, L
Goldstein, AM
Haiman, CA
Hallmans, G
Hankinson, SE
Harris, CC
Henriksson, R
Holly, EA
Hong, YC
Hoover, RN
Hsiung, CA
Hu, N
Hu, W
Hunter, DJ
Hutchinson, A
Jenab, M
Johansen, C
Khaw, KT
Kim, HN
Kim, YH
Kim, YT
Klein, AP
Klein, R
Koh, WP
Kolonel, LN
Kooperberg, C
Kraft, P
Krogh, V
Kurtz, RC
LaCroix, A
Lan, Q
Landi, MT
Le Marchand, L
Li, DH
Liang, XL
Liao, LM
Lin, DX
Liu, JJ
Lissowska, J
Lu, LG
Magliocco, AM
Malats, N
Matsuo, K
McNeill, LH
McWilliams, RR
Melin, BS
Mirabello, L
Moore, L
Olson, SH
Orlow, I
Park, JY
Patino-Garcia, A
Peplonska, B
Peters, U
Petersen, GM
Pooler, L
Prescott, J
Prokunina-Olsson, L
Purdue, MP
Qiao, YL
Rajaraman, P
Real, FX
Riboli, E
Risch, HA
Rodriguez-Santiago, B
Ruder, AM
Savage, SA
Schumacher, F
Schwartz, AG
Schwartz, KL
Seow, A
Setiawan, VW
Severi, G
Shen, H
Sheng, X
Shin, MH
Shu, XO
Silverman, DT
Spitz, MR
Stevens, VL
Stolzenberg-Solomon, R
Stram, D
Tang, ZZ
Taylor, PR
Teras, LR
Tobias, GS
Van den Berg, D
Visvanathan, K
Wacholder, S
Wang, JC
Wang, ZM
Wentzensen, N
Wheeler, W
White, E
Wiencke, JK
Wolpin, BM
Wong, MP
Wu, C
Wu, TC
Wu, XF
Wu, YL
Wunder, JS
Xia, L
Yang, HP
Yang, PC
Yu, K
Zanetti, KA
Zeleniuch-Jacquotte, A
Zheng, W
Zhou, B
Ziegler, RG
Perez-Jurado, LA
Caporaso, NE
Rothman, N
Tucker, M
Dean, MC
Yeager, M
Chanock, SJ
AF Machiela, Mitchell J.
Zhou, Weiyin
Karlins, Eric
Sampson, Joshua N.
Freedman, Neal D.
Yang, Qi
Hicks, Belynda
Dagnall, Casey
Hautman, Christopher
Jacobs, Kevin B.
Abnet, Christian C.
Aldrich, Melinda C.
Amos, Christopher
Amundadottir, Laufey T.
Arslan, Alan A.
Beane-Freeman, Laura E.
Berndt, Sonja I.
Black, Amanda
Blot, William J.
Bock, Cathryn H.
Bracci, Paige M.
Brinton, Louise A.
Bueno-de-Mesquita, H. Bas
Burdett, Laurie
Buring, Julie E.
Butler, Mary A.
Canzian, Federico
Carreon, Tania
Chaffee, Kari G.
Chang, I-Shou
Chatterjee, Nilanjan
Chen, Chu
Chen, Constance
Chen, Kexin
Chung, Charles C.
Cook, Linda S.
Bou, Marta Crous
Cullen, Michael
Davis, Faith G.
De Vivo, Immaculata
Ding, Ti
Doherty, Jennifer
Duell, Eric J.
Epstein, Caroline G.
Fan, Jin-Hu
Figueroa, Jonine D.
Fraumeni, Joseph F.
Friedenreich, Christine M.
Fuchs, Charles S.
Gallinger, Steven
Gao, Yu-Tang
Gapstur, Susan M.
Garcia-Closas, Montserrat
Gaudet, Mia M.
Gaziano, J. Michael
Giles, Graham G.
Gillanders, Elizabeth M.
Giovannucci, Edward L.
Goldin, Lynn
Goldstein, Alisa M.
Haiman, Christopher A.
Hallmans, Goran
Hankinson, Susan E.
Harris, Curtis C.
Henriksson, Roger
Holly, Elizabeth A.
Hong, Yun-Chul
Hoover, Robert N.
Hsiung, Chao A.
Hu, Nan
Hu, Wei
Hunter, David J.
Hutchinson, Amy
Jenab, Mazda
Johansen, Christoffer
Khaw, Kay-Tee
Kim, Hee Nam
Kim, Yeul Hong
Kim, Young Tae
Klein, Alison P.
Klein, Robert
Koh, Woon-Puay
Kolonel, Laurence N.
Kooperberg, Charles
Kraft, Peter
Krogh, Vittorio
Kurtz, Robert C.
LaCroix, Andrea
Lan, Qing
Landi, Maria Teresa
Le Marchand, Loic
Li, Donghui
Liang, Xiaolin
Liao, Linda M.
Lin, Dongxin
Liu, Jianjun
Lissowska, Jolanta
Lu, Lingeng
Magliocco, Anthony M.
Malats, Nuria
Matsuo, Keitaro
McNeill, Lorna H.
McWilliams, Robert R.
Melin, Beatrice S.
Mirabello, Lisa
Moore, Lee
Olson, Sara H.
Orlow, Irene
Park, Jae Yong
Patino-Garcia, Ana
Peplonska, Beata
Peters, Ulrike
Petersen, Gloria M.
Pooler, Loreall
Prescott, Jennifer
Prokunina-Olsson, Ludmila
Purdue, Mark P.
Qiao, You-Lin
Rajaraman, Preetha
Real, Francisco X.
Riboli, Elio
Risch, Harvey A.
Rodriguez-Santiago, Benjamin
Ruder, Avima M.
Savage, Sharon A.
Schumacher, Fredrick
Schwartz, Ann G.
Schwartz, Kendra L.
Seow, Adeline
Setiawan, Veronica Wendy
Severi, Gianluca
Shen, Hongbing
Sheng, Xin
Shin, Min-Ho
Shu, Xiao-Ou
Silverman, Debra T.
Spitz, Margaret R.
Stevens, Victoria L.
Stolzenberg-Solomon, Rachael
Stram, Daniel
Tang, Ze-Zhong
Taylor, Philip R.
Teras, Lauren R.
Tobias, Geoffrey S.
Van den Berg, David
Visvanathan, Kala
Wacholder, Sholom
Wang, Jiu-Cun
Wang, Zhaoming
Wentzensen, Nicolas
Wheeler, William
White, Emily
Wiencke, John K.
Wolpin, Brian M.
Wong, Maria Pik
Wu, Chen
Wu, Tangchun
Wu, Xifeng
Wu, Yi-Long
Wunder, Jay S.
Xia, Lucy
Yang, Hannah P.
Yang, Pan-Chyr
Yu, Kai
Zanetti, Krista A.
Zeleniuch-Jacquotte, Anne
Zheng, Wei
Zhou, Baosen
Ziegler, Regina G.
Perez-Jurado, Luis A.
Caporaso, Neil E.
Rothman, Nathaniel
Tucker, Margaret
Dean, Michael C.
Yeager, Meredith
Chanock, Stephen J.
TI Female chromosome X mosaicism is age-related and preferentially affects
the inactivated X chromosome
SO NATURE COMMUNICATIONS
LA English
DT Article
ID DETECTABLE CLONAL MOSAICISM; SOMATIC MOSAICISM; HUMAN GENOME; CANCER;
BLOOD; METHYLATION; CELLS; HEMATOPOIESIS; ANEUPLOIDIES; MUTATION
AB To investigate large structural clonal mosaicism of chromosome X, we analysed the SNP microarray intensity data of 38,303 women from cancer genome-wide association studies (20,878 cases and 17,425 controls) and detected 124 mosaic X events >2 Mb in 97 (0.25%) women. Here we show rates for X-chromosome mosaicism are four times higher than mean autosomal rates; X mosaic events more often include the entire chromosome and participants with X events more likely harbour autosomal mosaic events. X mosaicism frequency increases with age (0.11% in 50-year olds; 0.45% in 75-year olds), as reported for Y and autosomes. Methylation array analyses of 33 women with X mosaicism indicate events preferentially involve the inactive X chromosome. Our results provide further evidence that the sex chromosomes undergo mosaic events more frequently than autosomes, which could have implications for understanding the underlying mechanisms of mosaic events and their possible contribution to risk for chronic diseases.
C1 [Machiela, Mitchell J.; Zhou, Weiyin; Karlins, Eric; Sampson, Joshua N.; Freedman, Neal D.; Yang, Qi; Hicks, Belynda; Dagnall, Casey; Hautman, Christopher; Abnet, Christian C.; Amundadottir, Laufey T.; Beane-Freeman, Laura E.; Berndt, Sonja I.; Black, Amanda; Brinton, Louise A.; Burdett, Laurie; Chatterjee, Nilanjan; Chung, Charles C.; Cullen, Michael; Epstein, Caroline G.; Figueroa, Jonine D.; Fraumeni, Joseph F.; Goldin, Lynn; Goldstein, Alisa M.; Hoover, Robert N.; Hu, Nan; Hu, Wei; Hutchinson, Amy; Lan, Qing; Landi, Maria Teresa; Liao, Linda M.; Mirabello, Lisa; Moore, Lee; Prokunina-Olsson, Ludmila; Purdue, Mark P.; Rajaraman, Preetha; Savage, Sharon A.; Seow, Adeline; Silverman, Debra T.; Stolzenberg-Solomon, Rachael; Taylor, Philip R.; Tobias, Geoffrey S.; Wacholder, Sholom; Wang, Zhaoming; Wentzensen, Nicolas; Yang, Hannah P.; Yu, Kai; Ziegler, Regina G.; Caporaso, Neil E.; Rothman, Nathaniel; Tucker, Margaret; Dean, Michael C.; Yeager, Meredith; Chanock, Stephen J.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Zhou, Weiyin; Karlins, Eric; Yang, Qi; Hicks, Belynda; Dagnall, Casey; Hautman, Christopher; Jacobs, Kevin B.; Burdett, Laurie; Chung, Charles C.; Cullen, Michael; Hutchinson, Amy; Wang, Zhaoming; Yeager, Meredith] Leidos Biomed Res Inc, Div Canc Epidemiol & Genet, Natl Canc Inst, Canc Genom Res Lab, Bethesda, MD 20892 USA.
[Jacobs, Kevin B.] Bioinformed LLC, Gaithersburg, MD 20877 USA.
[Aldrich, Melinda C.] Vanderbilt Univ, Sch Med, Dept Thorac Surg, Nashville, TN 37232 USA.
[Aldrich, Melinda C.; Blot, William J.; Zheng, Wei] Vanderbilt Univ, Med Ctr, Vanderbilt Epidemiol Ctr, Dept Med,Div Epidemiol, Nashville, TN 37232 USA.
[Amos, Christopher] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Div Canc Prevent & Populat Sci, Houston, TX 77030 USA.
[Arslan, Alan A.] NYU, Sch Med, Dept Obstet & Gynecol, New York, NY 10016 USA.
[Arslan, Alan A.] NYU, Sch Med, Dept Environm Med, New York, NY 10016 USA.
[Arslan, Alan A.; Zeleniuch-Jacquotte, Anne] NYU, Inst Canc, New York, NY 10016 USA.
[Blot, William J.] Int Epidemiol Inst, Rockville, MD 20850 USA.
[Bock, Cathryn H.; Schwartz, Ann G.] Wayne State Univ, Sch Med, Karmanos Canc Inst, Detroit, MI 48201 USA.
[Bock, Cathryn H.; Schwartz, Ann G.] Wayne State Univ, Sch Med, Dept Oncol, Detroit, MI 48201 USA.
[Bracci, Paige M.; Holly, Elizabeth A.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA.
[Bueno-de-Mesquita, H. Bas] Natl Inst Publ Hlth & Environm RIVM, Dept Determinants Chron Dis DCD, Bilthoven 3721, Netherlands.
[Bueno-de-Mesquita, H. Bas] Univ Med Ctr, Dept Gastroenterol & Hepatol, NL-3584 CX Utrecht, Netherlands.
[Bueno-de-Mesquita, H. Bas] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Dept Epidemiol & Biostat, London SW7 2AZ, England.
[Bueno-de-Mesquita, H. Bas] Univ Malaya, Fac Med, Dept Social & Prevent Med, Kuala Lumpur 50603, Malaysia.
[Buring, Julie E.] Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA.
[Butler, Mary A.; Carreon, Tania; Ruder, Avima M.] NIOSH, Ctr Dis Control & Prevent, Cincinnati, OH 45226 USA.
[Canzian, Federico] German Canc Res Ctr, Div Canc Epidemiol, D-69120 Heidelberg, Germany.
[Chaffee, Kari G.; Petersen, Gloria M.] Mayo Clin, Dept Hlth Sci Res, Rochester, MN 55905 USA.
[Chang, I-Shou] Natl Hlth Res Inst, Natl Inst Canc Res, Zhunan 35053, Taiwan.
[Chen, Chu; Kooperberg, Charles; LaCroix, Andrea; Peters, Ulrike; White, Emily] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA.
[Chen, Constance; Bou, Marta Crous; De Vivo, Immaculata; Hunter, David J.; Kraft, Peter; Prescott, Jennifer] Harvard Univ, Sch Publ Hlth, Program Genet Epidemiol & Stat Genet, Boston, MA 02115 USA.
[Chen, Kexin] Tianjin Med Univ, Canc Inst & Hosp, Dept Epidemiol & Biostat, Tianjin 300040, Peoples R China.
[Cook, Linda S.] Univ New Mexico, Albuquerque, NM 87131 USA.
[Bou, Marta Crous; De Vivo, Immaculata; Fuchs, Charles S.; Giovannucci, Edward L.; Hankinson, Susan E.; Hunter, David J.; Prescott, Jennifer; Wolpin, Brian M.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA.
[Bou, Marta Crous; De Vivo, Immaculata; Fuchs, Charles S.; Giovannucci, Edward L.; Hankinson, Susan E.; Hunter, David J.; Prescott, Jennifer; Wolpin, Brian M.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Davis, Faith G.] Univ Alberta, Sch Publ Hlth, Dept Publ Hlth Sci, Edmonton, AB T6G 2R3, Canada.
[Ding, Ti; Tang, Ze-Zhong] Shanxi Canc Hosp, Taiyuan 030013, Shanxi, Peoples R China.
[Doherty, Jennifer] Dartmouth Coll, Geisel Sch Med, Lebanon, NH 03755 USA.
[Duell, Eric J.] Catalan Inst Oncol ICO IDIBELL, Bellvitge Biomed Res Inst, Canc Epidemiol Res Program, Unit Nutr & Canc, Barcelona 08908, Spain.
Shanghai Canc Inst, Shanghai 200032, Peoples R China.
[Friedenreich, Christine M.] Alberta Hlth Serv, Canc Control Alberta, Dept Populat Hlth Res, Calgary, AB T2N 2T9, Canada.
[Fuchs, Charles S.; Wolpin, Brian M.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA.
[Gallinger, Steven] Samuel Lunenfeld Res Inst, Fred A Litwin Ctr Canc Genet, Toronto, ON M5G 1X5, Canada.
[Gao, Yu-Tang] Shanghai Jiao Tong Univ, Sch Med, Renji Hosp, Shanghai Canc Inst,Dept Epidemiol, Shanghai 200032, Peoples R China.
[Gapstur, Susan M.; Gaudet, Mia M.; Stevens, Victoria L.; Teras, Lauren R.] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30303 USA.
[Garcia-Closas, Montserrat] Inst Canc Res, Div Genet & Epidemiol, Sutton SM2 5NG, Surrey, England.
[Garcia-Closas, Montserrat] Inst Canc Res, Breakthrough Breast Canc Ctr, Sutton SM2 5NG, Surrey, England.
[Gaziano, J. Michael] Brigham & Womens Hosp, Dept Med, Div Prevent Med, Boston, MA 02115 USA.
[Gaziano, J. Michael] Brigham & Womens Hosp, Dept Med, Div Aging, Boston, MA 02115 USA.
[Gaziano, J. Michael] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Gaziano, J. Michael] Vet Affairs Boston Healthcare Syst, VA Cooperat Studies Programs, Massachusetts Vet Epidemiol Res & Informat Ctr, Boston, MA 02130 USA.
[Giles, Graham G.; Severi, Gianluca] Univ Melbourne, Melbourne Sch Populat & Global Hlth, Canc Epidemiol Ctr, Canc Council Victoria, Melbourne, Vic 3010, Australia.
[Giles, Graham G.; Severi, Gianluca] Univ Melbourne, Melbourne Sch Populat & Global Hlth, Ctr Epidemiol & Biostat, Melbourne, Vic 3010, Australia.
[Gillanders, Elizabeth M.; Zanetti, Krista A.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Giovannucci, Edward L.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Haiman, Christopher A.; Schumacher, Fredrick; Setiawan, Veronica Wendy; Stram, Daniel; Van den Berg, David] Univ So Calif, Keck Sch Med, Dept Prevent Med, Div Biostat, Los Angeles, CA 90033 USA.
[Hallmans, Goran] Umea Univ, Dept Publ Hlth & Clin Med Nutr Res, S-90187 Umea, Sweden.
[Hankinson, Susan E.] Univ Massachusetts, Sch Publ Hlth & Hlth Sci, Div Biostat & Epidemiol, Amherst, MA 01003 USA.
[Harris, Curtis C.] NCI, Ctr Canc Res, Human Carcinogenesis Lab, Bethesda, MD 20892 USA.
[Henriksson, Roger; Melin, Beatrice S.] Umea Univ, Dept Radiat Sci Oncol, S-90187 Umea, Sweden.
[Hong, Yun-Chul] Seoul Natl Univ, Coll Med, Dept Prevent Med, Seoul 151742, South Korea.
[Hsiung, Chao A.] Natl Hlth Res Inst, Inst Populat Hlth Sci, Zhunan 35053, Taiwan.
[Hunter, David J.] Harvard & MIT, Broad Inst, Cambridge, MA 02142 USA.
[Jenab, Mazda] WHO, IARC, F-69372 Lyon, France.
[Johansen, Christoffer] Rigshosp, Finsen Ctr, Oncol, DK-2100 Copenhagen, Denmark.
[Johansen, Christoffer] Danish Canc Soc, Res Ctr, Unit Survivorship Res, DK-2100 Copenhagen, Denmark.
[Khaw, Kay-Tee] Univ Cambridge, Sch Clin Med, Cambridge CB2 1TN, England.
[Kim, Hee Nam] Chonnam Natl Univ, Ctr Creat Biomed Scientists, Gwangju 500757, South Korea.
[Kim, Yeul Hong] Korea Univ, Anam Hosp, Coll Med, Dept Internal Med,Div Oncol Hematol, Seoul 151742, South Korea.
[Kim, Young Tae] Seoul Natl Univ, Coll Med, Canc Res Inst, Dept Thorac & Cardiovasc Surg, Seoul 03080, South Korea.
[Klein, Alison P.] Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21287 USA.
[Klein, Robert] Mem Sloan Kettering Canc Ctr, Program Canc Biol & Genet, New York, NY 10065 USA.
[Koh, Woon-Puay] Duke NUS Grad Med Sch, Singapore 169857, Singapore.
[Koh, Woon-Puay; Seow, Adeline] Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore 119077, Singapore.
[Kolonel, Laurence N.; Le Marchand, Loic] Univ Hawaii, Ctr Canc, Program Epidemiol, Honolulu, HI 96813 USA.
[Krogh, Vittorio] Fdn IRCCS Ist Nazl Tumori, I-20133 Milan, Italy.
[Kurtz, Robert C.] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10065 USA.
[Li, Donghui] Univ Texas MD Anderson Canc Ctr, Dept Gastrointestinal Med Oncol, Houston, TX 77030 USA.
[Liang, Xiaolin; Olson, Sara H.; Orlow, Irene] Mem Sloan Kettering Canc Ctr, New York, NY 10065 USA.
[Lin, Dongxin; Wu, Chen] Chinese Acad Med Sci, Canc Inst & Hosp, Dept Etiol & Carcinogenesis, Beijing 100730, Peoples R China.
[Lin, Dongxin; Wu, Chen] Peking Union Med Coll, Beijing 100730, Peoples R China.
[Lin, Dongxin; Wu, Chen] Chinese Acad Med Sci, Canc Inst & Hosp, State Key Lab Mol Oncol, Beijing 100730, Peoples R China.
[Liu, Jianjun] Genome Inst Singapore, Dept Human Genet, Singapore 138672, Singapore.
[Liu, Jianjun] Anhui Med Univ, Sch Life Sci, Hefei 230032, Peoples R China.
[Lissowska, Jolanta] Maria Sklodowska Curie Canc Ctr & Inst Oncol, Dept Canc Epidemiol & Prevent, PL-02781 Warsaw, Poland.
[Lu, Lingeng; Risch, Harvey A.] Yale Univ, Sch Publ Hlth, New Haven, CT 06510 USA.
[Magliocco, Anthony M.] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA.
[Malats, Nuria; Real, Francisco X.] Spanish Natl Canc Res Ctr CNIO, Madrid 28029, Spain.
[Matsuo, Keitaro] Aichi Canc Ctr, Res Inst, Div Mol Med, Nagoya, Aichi 4648681, Japan.
[McNeill, Lorna H.] Univ Texas MD Anderson Canc Ctr, Duncan Family Inst, Dept Hlth Dispar Res, Div OVP Canc Prevent & Populat Sci, Houston, TX 77030 USA.
[McNeill, Lorna H.] Univ Texas MD Anderson Canc Ctr, Duncan Family Inst, Ctr Community Engaged Translat Res, Houston, TX 77030 USA.
[McWilliams, Robert R.] Mayo Clin, Dept Oncol, Rochester, MN 55905 USA.
[Park, Jae Yong] Kyungpook Natl Univ, Med Ctr, Lung Canc Ctr, Daegu 101, South Korea.
[Patino-Garcia, Ana] Univ Navarra, Univ Navarra Clin, Navarra Inst Hlth Res, IdiSNA,Dept Pediat, E-31080 Pamplona, Spain.
[Peplonska, Beata] Nofer Inst Occupat Med, PL-91348 Lodz, Poland.
[Pooler, Loreall; Sheng, Xin; Xia, Lucy] Univ So Calif, Los Angeles, CA 90007 USA.
[Qiao, You-Lin] Chinese Acad Med Sci, Canc Inst Hosp, Dept Epidemiol, Beijing 100730, Peoples R China.
[Real, Francisco X.; Rodriguez-Santiago, Benjamin; Perez-Jurado, Luis A.] Univ Pompeu Fabra, Dept Ciencies Expt & Salut, Barcelona 08002, Spain.
[Riboli, Elio] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Div Epidemiol & Biostat, London SW7 2AZ, England.
[Rodriguez-Santiago, Benjamin; Perez-Jurado, Luis A.] Ctr Invest Biomed Red Enfermedades Raras CIBERER, Barcelona 28029, Spain.
[Rodriguez-Santiago, Benjamin] QGenomics, Quantitat Genom Med Lab, Barcelona 08003, Spain.
[Schwartz, Kendra L.] Wayne State Univ, Sch Med, Karmanos Canc Inst, Detroit, MI 48201 USA.
[Schwartz, Kendra L.] Wayne State Univ, Sch Med, Dept Family Med & Publ Hlth Sci, Detroit, MI 48201 USA.
[Severi, Gianluca] Human Genet Fdn HuGeF, I-10126 Turin, Italy.
[Shen, Hongbing] Nanjing Med Univ, Jiangsu Key Lab Canc Biomarkers Prevent & Treatme, Nanjing 210029, Jiangsu, Peoples R China.
[Shen, Hongbing] Nanjing Med Univ, Sch Publ Hlth, Dept Epidemiol, Nanjing 210029, Jiangsu, Peoples R China.
[Shin, Min-Ho] Chonnam Natl Univ, Sch Med, Dept Prevent Med, Gwanju 501746, South Korea.
[Shu, Xiao-Ou] Vanderbilt Univ, Med Ctr, Vanderbilt Ingram Canc Ctr, Vanderbilt Epidemiol Ctr,Dept Med, Nashville, TN 37232 USA.
[Spitz, Margaret R.] Baylor Coll Med, Houston, TX 77030 USA.
[Visvanathan, Kala] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD 21218 USA.
[Wang, Jiu-Cun] Fudan Univ, Sch Life Sci, Key Lab Contemporary Anthropol, Minist Educ, Shanghai 200433, Peoples R China.
[Wang, Jiu-Cun] Fudan Univ, Sch Life Sci, State Key Lab Genet Engn, Shanghai 200433, Peoples R China.
[Wheeler, William] Informat Management Serv Inc, Calverton, MD 20904 USA.
[Wiencke, John K.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Wong, Maria Pik] Univ Hong Kong, Li Ka Shing Fac Med, Dept Pathol, Hong Kong, Hong Kong, Peoples R China.
[Wu, Tangchun] Huazhong Univ Sci & Technol, Sch Publ Hlth, Inst Occupat Med, Wuhan 430400, Peoples R China.
[Wu, Tangchun] Huazhong Univ Sci & Technol, Sch Publ Hlth, Key Lab Environm & Hlth, Minist Educ, Wuhan 430400, Peoples R China.
[Wu, Xifeng] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA.
[Wu, Yi-Long] Guangdong Gen Hosp, Guangdong Lung Canc Inst, Guangzhou 515200, Guangdong, Peoples R China.
[Wu, Yi-Long] Guangdong Acad Med Sci, Guangzhou 515200, Guangdong, Peoples R China.
[Wunder, Jay S.] Washington Univ, Sch Med, Div Urol Surg, St Louis, MO 63110 USA.
[Yang, Pan-Chyr] Natl Taiwan Univ, Coll Med, Dept Internal Med, Taipei 10617, Taiwan.
[Zeleniuch-Jacquotte, Anne] NYU, Sch Med, Dept Populat Hlth, New York, NY 10016 USA.
[Zhou, Baosen] China Med Univ, Sch Publ Hlth, Dept Epidemiol, Shenyang 110001, Peoples R China.
RP Chanock, SJ (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
EM chanocks@mail.nih.gov
RI Krogh, Vittorio/K-2628-2016; Abnet, Christian/C-4111-2015; Tobias,
Geoffrey/M-4135-2016; Qiao, You-Lin/B-4139-2012; Zheng, Wei/O-3351-2013;
Beane Freeman, Laura/C-4468-2015
OI Krogh, Vittorio/0000-0003-0122-8624; Abnet,
Christian/0000-0002-3008-7843; Tobias, Geoffrey/0000-0002-2878-8253;
Qiao, You-Lin/0000-0001-6380-0871; Zheng, Wei/0000-0003-1226-070X; Beane
Freeman, Laura/0000-0003-1294-4124
FU Broad Center for Genotyping and Analysis [U01HG04424]; Cancer Prevention
Study-II (American Cancer Society); Center for Inherited Disease
Research [U01HG004438, HHSN268200782096C]; Endometrial cancer [ROl CA
134958]; Fred Hutchinson Cancer Research Center (funds from the Fred
Hutchinson Cancer Research Center and National Institute of Health) [R35
CA 39779, RO1 CA 75977, R03 CA 80636, NO1 HD 2 3166, KO5 CA 92002, CA
105212, RO1 CA87538]; Fudan Lung Cancer Study Ministry of Health
[201002007]; Ministry of Science and Technology [2011BAIO9B00]; National
S&T Major Special Project [2011ZX09102-010-01]; China National High-Tech
Research and Development Program [2012AA02A517, 2012AA02A518]; National
Science Foundation of China [30890034]; National Basic Research Program
[2012CB944600]; Scientific and Technological Support Plans from Jiangsu
Province [BE2010715]; Genes and Environment in Lung Cancer, Singapore
Study (National Medical Research Council Singapore) [NMRC/0897/2004,
NMRC/1075/2006]; Agency for Science, Technology and Research (A*STAR) of
Singapore; National Research Program on Genomic Medicine in Taiwan
[DOH98-TD-G-111-015]; National Research Program for Biopharmaceuticals
in Taiwan [DOH 100-TD-PB-111TM013]; National Science Council, Taiwan
[NSC 100-2319-B-400-001]; Guangdong Study (Foundation of Guangdong
Science and Technology Department [2006B60101010, 2007A032000002,
2011A030400010]; Guangzhou Science and Information Technology Bureau
[2011Y2-00014]; Chinese Lung Cancer Research Foundation; National
Natural Science Foundation of China [81101549]; Natural Science
Foundation of Guangdong Province [S2011010000792]; Hong Kong Study
(General Research Fund of Research Grant Council, Hong Kong) [781511M];
Intramural Research Program of the Division of Cancer Epidemiology and
Genetics, National Cancer Institute, NIH; Intramural Research Program of
the NIH, National Library of Medicine; Intramural Research Program of
the National Institute for Occupational Safety and Health; Ministry of
Health, Labor, and Welfare for Research on Applying Health Technology;
National Cancer Center Research and Development Fund; NCI
[R01-CA121210]; Korea Health Technology R&D Project (Korea Health
Industry Development Institute (KHIDI); Ministry of Health & Welfare,
Republic of Korea [HI14C0066]; Ministry of Health [201002007]; Melanoma
[NCI R29CA70334, R01CA100264, P50CA093459]; National Research Foundation
of Korea (NRF); Korea government (MSIP) [NRF-2014R1A2A2A05003665]; NLCS
(China National High-Tech Research and Development Program Grant
[2009AA022705]; Priority Academic Program Development of Jiangsu Higher
Education Institution; National Key Basic Research Program Grant
[2011CB503805]; Nurses' Health Study [P01 CA87969, ROl CA49449]; Yunnan
Lung Cancer Study (Intramural program of U.S. National Institutes of
Health; National Cancer Institute; NIH/NCI [K07 CA 172294]; Women's
Health Initiative (National Heart, Lung, and Blood Institute, National
Institutes of Health, U.S. Department of Health and Human Services)
[HHSN268201100046C, HHSN268201100001C, HHSN268201100002C,
HHSN268201100003C, HHSN268201100004C, HHSN271201100004C]; Tianjin Cancer
Institute and Hospital, National Foundation for Cancer Research US;
[U01 CA164973]; [U01 CA098758]
FX Some individuals, studies, and centers received individual support as
follows: Broad Center for Genotyping and Analysis (U01HG04424); Cancer
Prevention Study-II (American Cancer Society); Center for Inherited
Disease Research (U01HG004438, HHSN268200782096C); Endometrial cancer
(ROl CA 134958); Fred Hutchinson Cancer Research Center (funds from the
Fred Hutchinson Cancer Research Center and National Institute of Health
grants (R35 CA 39779, RO1 CA 75977, R03 CA 80636, NO1 HD 2 3166, KO5 CA
92002, CA 105212 and RO1 CA87538)); Fudan Lung Cancer Study (Ministry of
Health (201002007); Ministry of Science and Technology (2011BAIO9B00);
National S&T Major Special Project (2011ZX09102-010-01); China National
High-Tech Research and Development Program (2012AA02A517, 2012AA02A518);
National Science Foundation of China (30890034); National Basic Research
Program (2012CB944600); Scientific and Technological Support Plans from
Jiangsu Province (BE2010715)); Gene-Environment Association Studies
(Coordinating Center:U01 HG004446, Manuscript preparation:
P01-GM099568); Genes and Environment in Lung Cancer, Singapore Study
(National Medical Research Council Singapore grant (NMRC/0897/2004,
NMRC/1075/2006); Agency for Science, Technology and Research (A*STAR) of
Singapore); Genetic Epidemiological Study of Lung Adenocarcinoma
(National Research Program on Genomic Medicine in Taiwan
(DOH98-TD-G-111-015); National Research Program for Biopharmaceuticals
in Taiwan (DOH 100-TD-PB-111TM013); National Science Council, Taiwan
(NSC 100-2319-B-400-001)); Guangdong Study (Foundation of Guangdong
Science and Technology Department (2006B60101010, 2007A032000002,
2011A030400010); Guangzhou Science and Information Technology Bureau
(2011Y2-00014); Chinese Lung Cancer Research Foundation; National
Natural Science Foundation of China (81101549); Natural Science
Foundation of Guangdong Province (S2011010000792)); Hong Kong Study
(General Research Fund of Research Grant Council, Hong Kong (781511M));
Intramural Research Program of the Division of Cancer Epidemiology and
Genetics, National Cancer Institute, NIH; Intramural Research Program of
the NIH, National Library of Medicine; Intramural Research Program of
the National Institute for Occupational Safety and Health; Japanese
Female Lung Cancer Collaborative Study (Grants-in-Aid from the Ministry
of Health, Labor, and Welfare for Research on Applying Health Technology
and for the 3rd-term Comprehensive 10-year Strategy for Cancer Control;
National Cancer Center Research and Development Fund; Grant-in-Aid for
Scientific Research on Priority Areas and on Innovative Area from the
Ministry of Education, Science, Sports, Culture and Technology of Japan;
NCI (R01-CA121210)); Korea Health Technology R&D Project (Korea Health
Industry Development Institute (KHIDI), funded by the Ministry of Health
& Welfare, Republic of Korea (HI14C0066)); Lung cancer (ZO1CP010200);
Lung health (U01HG004738); Ministry of Health (201002007); Ministry of
Science and Technology (2011BAIO9B00); Melanoma (NCI R29CA70334,
R01CA100264, P50CA093459); Multiethnic Cohort Study (Infrastructure
grant (U01 CA164973) and U01 CA098758); National Research Foundation of
Korea (NRF) (funded by the Korea government (MSIP)
(NRF-2014R1A2A2A05003665)); NLCS (China National High-Tech Research and
Development Program Grant (2009AA022705); Priority Academic Program
Development of Jiangsu Higher Education Institution; National Key Basic
Research Program Grant (2011CB503805)); Nurses' Health Study (P01
CA87969, ROl CA49449); Nurses' Health Study II (UM1 CA176726, ROl 6;
7262); OpPancreatic cancer (Mayo Clinic SPORE in Pancreatic Cancer:
P50CA102701); Prostate cancer (U01HG004726, NCI: CA63464, CA54281,
CA1326792, RC2 CA148085); Shanghai Women's Health Cohort Study (National
Institutes of Health (R37 CA70867); National Cancer Institute intramural
research program; NCI Intramural Research Program contract (NO2
CP1101066)); Shenyang Lung Cancer Study (National Nature Science
Foundation of China (81102194); Liaoning Provincial Department of
Education (LS2010168); China Medical Board (00726)); Singapore Chinese
Health Study (NIH grants: NCI ROl CA55069, R35 CA53890, ROl CA80205, and
ROl CA144034); South Korea Multi-Center Lung Cancer Study (National
Research Foundation of Korea (NRF) grant funded by the Korea government
(MEST) (2011-0016106); National R&D Program for Cancer Control, Ministry
of Health &Welfare, Republic of Korea (0720550-2); (A010250)); Tianjin
Lung Cancer Study (Program for Changjiang Scholars and Innovative
Research Team in University (PCSIRT); China (IRT1076), Tianjin Cancer
Institute and Hospital, National Foundation for Cancer Research US);
University of Texas MD Anderson Cancer Center (institutional support for
the Center for Translational and Public Health Genomics (NIH grant P50
CA 91846)); Women's Health Initiative (National Heart, Lung, and Blood
Institute, National Institutes of Health, U.S. Department of Health and
Human Services contracts HHSN268201100046C, HHSN268201100001C,
HHSN268201100002C, HHSN268201100003C, HHSN268201100004C, and
HHSN271201100004C); Wuhan lung cancer study (National Key Basic Research
and Development Program (2011CB503800)) and Yunnan Lung Cancer Study
(Intramural program of U.S. National Institutes of Health; National
Cancer Institute). Melinda C. Aldrich was supported by NIH/NCI grant K07
CA 172294. We would like to thank the participants and staff of the NHS
and NHSII cohorts for their valuable contributions as well as the
following state registries for their help: AL, AZ, AR, CA, CO, CT, DE,
FL, GA, ID, IL, IN, IA, KY, LA, ME, MD, MA, MI, NE, NH, NJ, NY, NC, ND,
OH, OK, OR, PA, RI, SC, TN, TX, VA, WA, WY. This study was approved by
the Connecticut Department of Public Health (DPH) Human Investigations
Committee. Certain data used in this publication were obtained from the
DPH. The authors assume full responsibility for the analyses and
interpretation of these data. The Women's Health Initiative would like
to acknowledge the following individuals for their participation:
Program Office: (National Heart, Lung, and Blood Institute, Bethesda,
Maryland) Jacques Rossouw, Shari Ludlam, Dale Burwen, Joan McGowan,
Leslie Ford, and Nancy Geller; Clinical Coordinating Center: (Fred
Hutchinson Cancer Research Center, Seattle, WA) Garnet Anderson, Ross
Prentice, Andrea LaCroix, and Charles Kooperberg; Investigators and
Academic Centers: (Brigham and Women's Hospital, Harvard Medical School,
Boston, MA) JoAnn E. Manson; (MedStar Health Research Institute/Howard
University, Washington, DC) Barbara V. Howard; (Stanford Prevention
Research Center, Stanford, CA). Marcia L. Stefanick; (The Ohio State
University, Columbus, OH) Rebecca Jackson; (University of Arizona,
Tucson/Phoenix, AZ) Cynthia A. Thomson; (University at Buffalo, Buffalo,
NY) Jean Wactawski-Wende; (University of Florida,
Gainesville/Jacksonville, FL) Marian Limacher; (University of Iowa, Iowa
City/Davenport, IA) Robert Wallace; (University of Pittsburgh,
Pittsburgh, PA) Lewis Kuller; (Wake Forest University School of
Medicine, Winston-Salem, NC) Sally Shumaker.; Women's Health Initiative
Memory Study: (Wake Forest University School of Medicine, Winston-Salem,
NC) Sally Shumaker.
NR 40
TC 0
Z9 0
U1 13
U2 19
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2041-1723
J9 NAT COMMUN
JI Nat. Commun.
PD JUN 13
PY 2016
VL 7
AR 118431
DI 10.1038/ncomms118431
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DP3IY
UT WOS:000378387800001
ER
PT J
AU Xu, WP
Neckers, L
AF Xu, Wanping
Neckers, Len
TI Gr(i)p the ER to Stress Out Melanoma
SO CANCER CELL
LA English
DT Editorial Material
ID CANCER
AB Because of their elevated steady-state stress level, cancer cells are particularly sensitive to perturbation of mechanisms regulating protein homeostasis. In this issue, Cerezo and colleagues show that pharmacologic modulation of GRP78, master regulator of the unfolded protein response in the endoplasmic reticulum, can be exploited for cancer treatment.
C1 [Xu, Wanping; Neckers, Len] NCI, Urol Oncol Branch, Ctr Canc Res, 9000 Rockville Pike, Bethesda, MD 20892 USA.
RP Neckers, L (reprint author), NCI, Urol Oncol Branch, Ctr Canc Res, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM neckers@nih.gov
NR 10
TC 1
Z9 2
U1 0
U2 2
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1535-6108
EI 1878-3686
J9 CANCER CELL
JI Cancer Cell
PD JUN 13
PY 2016
VL 29
IS 6
BP 769
EP 771
DI 10.1016/j.ccell.2016.05.006
PG 3
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA DO7AB
UT WOS:000377933500001
PM 27300428
ER
PT J
AU Enewold, L
Thomas, A
AF Enewold, Lindsey
Thomas, Anish
TI Real-World Patterns of EGFR Testing and Treatment with Erlotinib for
Non-Small Cell Lung Cancer in the United States
SO PLOS ONE
LA English
DT Article
ID GROWTH-FACTOR RECEPTOR; RANDOMIZED PHASE-3 TRIAL; HISPANIC WHITE
PATIENTS; 1ST-LINE TREATMENT; OPEN-LABEL; AMERICAN SOCIETY; MUTATIONS;
CHEMOTHERAPY; GEFITINIB; ADENOCARCINOMA
AB Despite being the basis of one of the most effective interventions in lung cancer, little is known about the patterns of epidermal growth factor receptor (EGFR) mutation testing in the general population. We assessed the frequencies and determinants of EGFR testing and erlotinib treatment among a population-based sample. A random sample (n = 1,358) of patients diagnosed in 2010 with histologically-confirmed NSCLC, as reported to the Surveillance Epidemiology and End Results (SEER) program, had their medical records abstracted and treating physicians queried. Logistic regression was used to identify factors associated with EGFR testing and erlotinib treatment. Survival was examined using Cox proportional hazards regression. The frequency of EGFR testing was 16.8% overall and 22.6% for stage IV adenocarcinoma patients. Given an EGFR mutation, 33.6% of all patients and 48.3% of stage IV patients received erlotinib. Among stage IV patients, increased age, Medicaid/no/unknown insurance status, death within 2 months of diagnosis and comorbidity were inversely associated with EGFR testing; erlotinib treatment was less likely among smokers and patients with non-adenocarcinomas. EGFR-mutation was associated with improved survival, albeit only among stage IV adenocarcinomas. Less than a quarter of NSCLC patients diagnosed in 2010 received EGFR testing and less than half of the patients with EGFR-mutant stage IV tumors received erlotinib. Significant disparities were observed in EGFR mutation testing by health insurance status, comorbidity and age. A national strategy is imperative to ensure that resources and processes are in place to efficiently implement molecular testing of cancer.
C1 [Enewold, Lindsey] NCI, Healthcare Assessment Res Branch, Healthcare Delivery Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Thomas, Anish] NCI, Thorac & Gastrointestinal Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Enewold, L (reprint author), NCI, Healthcare Assessment Res Branch, Healthcare Delivery Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
EM lindsey.enewold@nih.gov
FU National Cancer Institute [HHSN261201000024C, HHSN261201000025C,
HHSN261201000032C, HHSN261201000027C, HHSN261201000026C,
HHSN261201000140C, HHSN261201000037C, HHSN261201000033C,
HHSN261201000034C, HHSN261201000035C, HHSN261201000029C,
HHSN261201000031C, HHSN261201000028C, HHSN261201000030C]
FX This work was supported by the Intramural Research Program of the
National Cancer Institute and National Cancer Institute contracts:
HHSN261201000024C; HHSN261201000025C, HHSN261201000032C,
HHSN261201000027C, HHSN261201000026C, HHSN261201000140C,
HHSN261201000037C, HHSN261201000033C, HHSN261201000034C,
HHSN261201000035C, HHSN261201000029C, HHSN261201000031C,
HHSN261201000028C, and HHSN261201000030C.
NR 33
TC 2
Z9 2
U1 3
U2 4
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUN 13
PY 2016
VL 11
IS 6
AR e0156728
DI 10.1371/journal.pone.0156728
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DO5KF
UT WOS:000377821300011
PM 27294665
ER
PT J
AU Semba, RD
Shardell, M
Trehan, I
Moaddel, R
Maleta, KM
Ordiz, MI
Kraemer, K
Khadeer, M
Ferrucci, L
Manary, MJ
AF Semba, Richard D.
Shardell, Michelle
Trehan, Indi
Moaddel, Ruin
Maleta, Kenneth M.
Ordiz, M. Isabel
Kraemer, Klaus
Khadeer, Mohammed
Ferrucci, Luigi
Manary, Mark J.
TI Metabolic alterations in children with environmental enteric dysfunction
SO SCIENTIFIC REPORTS
LA English
DT Article
ID FALSE DISCOVERY RATES; INTESTINAL PERMEABILITY; PHOSPHATIDYLCHOLINE;
ENTEROPATHY; TRYPTOPHAN; SEROTONIN; SPHINGOMYELINS; CITRULLINE;
DISORDERS; TAURINE
AB Environmental enteric dysfunction, an asymptomatic condition characterized by inflammation of the small bowel mucosa, villous atrophy, malabsorption, and increased intestinal permeability, is a major contributor to childhood stunting in low-income countries. Here we report the relationship of increased intestinal permeability with serum metabolites in 315 children without acute malnutrition, aged 12-59 months, in rural Malawi. Increased gut permeability was associated with significant differences in circulating metabolites that included lower serum phosphatidylcholines, sphingomyelins, tryptophan, ornithine, and citrulline, and elevated serum glutamate, taurine, and serotonin. Our findings suggest that environmental enteric dysfunction is characterized by alterations in important metabolites involved in growth and differentiation and gut function and integrity.
C1 [Semba, Richard D.] Johns Hopkins Univ, Wilmer Eye Inst, Sch Med, Baltimore, MD 21287 USA.
[Shardell, Michelle; Moaddel, Ruin; Khadeer, Mohammed; Ferrucci, Luigi] NIA, NIH, Baltimore, MD 21224 USA.
[Trehan, Indi; Ordiz, M. Isabel; Manary, Mark J.] Washington Univ, Dept Pediat, St Louis, MO 63110 USA.
[Trehan, Indi; Maleta, Kenneth M.; Manary, Mark J.] Univ Malawi, Sch Publ Hlth & Family Med, Coll Med, Blantyre, Malawi.
[Kraemer, Klaus] Sight & Life, CH-4002 Basel, Switzerland.
[Kraemer, Klaus] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA.
RP Semba, RD (reprint author), Johns Hopkins Univ, Wilmer Eye Inst, Sch Med, Baltimore, MD 21287 USA.
EM rdsemba@jhmi.edu
OI Maleta, Ken/0000-0002-2536-3938
FU Children's Discovery Institute; Hickey Family Foundation; National
Institutes of Health [R01 AG27012]; Intramural Branch of the National
Institute on Aging, Baltimore, Maryland
FX This work was supported by the Children's Discovery Institute, the
Hickey Family Foundation, the National Institutes of Health R01 AG27012
and the Intramural Branch of the National Institute on Aging, Baltimore,
Maryland.
NR 44
TC 4
Z9 4
U1 0
U2 2
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2045-2322
J9 SCI REP-UK
JI Sci Rep
PD JUN 13
PY 2016
VL 6
AR 28009
DI 10.1038/srep28009
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DO8MW
UT WOS:000378038700001
PM 27294788
ER
PT J
AU Guay, MD
Czaja, W
Aronova, MA
Leapman, RD
AF Guay, Matthew D.
Czaja, Wojciech
Aronova, Maria A.
Leapman, Richard D.
TI Compressed Sensing Electron Tomography for Determining Biological
Structure
SO SCIENTIFIC REPORTS
LA English
DT Article
ID CRYOELECTRON TOMOGRAPHY; RECONSTRUCTION; REGULARIZATION; TRANSFORMS; MRI
AB There has been growing interest in applying compressed sensing (CS) theory and practice to reconstruct 3D volumes at the nanoscale from electron tomography datasets of inorganic materials, based on known sparsity in the structure of interest. Here we explore the application of CS for visualizing the 3D structure of biological specimens from tomographic tilt series acquired in the scanning transmission electron microscope (STEM). CS-ET reconstructions match or outperform commonly used alternative methods in full and undersampled tomogram recovery, but with less significant performance gains than observed for the imaging of inorganic materials. We propose that this disparity stems from the increased structural complexity of biological systems, as supported by theoretical CS sampling considerations and numerical results in simulated phantom datasets. A detailed analysis of the efficacy of CS-ET for undersampled recovery is therefore complicated by the structure of the object being imaged. The numerical nonlinear decoding process of CS shares strong connections with popular regularized least-squares methods, and the use of such numerical recovery techniques for mitigating artifacts and denoising in reconstructions of fully sampled datasets remains advantageous. This article provides a link to the software that has been developed for CS-ET reconstruction of electron tomographic data sets.
C1 [Guay, Matthew D.] Univ Maryland, Dept Appl Math & Sci Computat, College Pk, MD 20742 USA.
[Czaja, Wojciech] Univ Maryland, Dept Math, College Pk, MD 20742 USA.
[Aronova, Maria A.; Leapman, Richard D.] Natl Inst Biomed Imaging & Bioengn, NIH, Bethesda, MD 20892 USA.
RP Guay, MD (reprint author), Univ Maryland, Dept Appl Math & Sci Computat, College Pk, MD 20742 USA.; Leapman, RD (reprint author), Natl Inst Biomed Imaging & Bioengn, NIH, Bethesda, MD 20892 USA.
EM mguay@math.umd.edu; leapmanr@mail.nih.gov
FU National Institute of Biomedical Imaging and Bioengineering, National
Institutes of Health; Defense Threat Reduction Agency [HDTRA1-13-1-0015]
FX This research was partially supported by the intramural program of the
National Institute of Biomedical Imaging and Bioengineering, National
Institutes of Health, and partially supported by Defense Threat
Reduction Agency grant HDTRA1-13-1-0015 to the University of Maryland.
NR 45
TC 2
Z9 2
U1 6
U2 8
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2045-2322
J9 SCI REP-UK
JI Sci Rep
PD JUN 13
PY 2016
VL 6
AR 27614
DI 10.1038/srep27614
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DO3AP
UT WOS:000377652800001
PM 27291259
ER
PT J
AU Wu, HE
Baumgardt, SL
Fang, J
Paterson, M
Liu, YA
Du, JH
Shi, Y
Qiao, SG
Bosnjak, ZJ
Warltier, DC
Kersten, JR
Ge, ZD
AF Wu, Hsiang-En
Baumgardt, Shelley L.
Fang, Juan
Paterson, Mark
Liu, Yanan
Du, Jianhai
Shi, Yang
Qiao, Shigang
Bosnjak, Zeljko J.
Warltier, David C.
Kersten, Judy R.
Ge, Zhi-Dong
TI Cardiomyocyte GTP Cyclohydrolase 1 Protects the Heart Against Diabetic
Cardiomyopathy
SO SCIENTIFIC REPORTS
LA English
DT Article
ID NITRIC-OXIDE SYNTHASE; POPULATION-BASED COHORT; REPERFUSION INJURY;
MORTALITY TRENDS; INDUCED CARDIOPROTECTION; PERMEABILITY TRANSITION;
ISCHEMIA-REPERFUSION; CARDIAC DYSFUNCTION; MYOCARDIAL-ISCHEMIA; 26S
PROTEASOME
AB Diabetic cardiomyopathy increases the risk of heart failure and death. At present, there are no effective approaches to preventing its development in the clinic. Here we report that reduction of cardiac GTP cyclohydrolase 1 (GCH1) degradation by genetic and pharmacological approaches protects the heart against diabetic cardiomyopathy. Diabetic cardiomyopathy was induced in C57BL/6 wild-type mice and transgenic mice with cardiomyocyte-specific overexpression of GCH1 with streptozotocin, and control animals were given citrate buffer. We found that diabetes-induced degradation of cardiac GCH1 proteins contributed to adverse cardiac remodeling and dysfunction in C57BL/6 mice, concomitant with decreases in tetrahydrobiopterin, dimeric and phosphorylated neuronal nitric oxide synthase, sarcoplasmic reticulum Ca2+ handling proteins, intracellular [Ca2+] i, and sarcoplasmic reticulum Ca2+ content and increases in phosphorylated p-38 mitogen-activated protein kinase and superoxide production. Interestingly, GCH-1 overexpression abrogated these detrimental effects of diabetes. Furthermore, we found that MG 132, an inhibitor for 26S proteasome, preserved cardiac GCH1 proteins and ameliorated cardiac remodeling and dysfunction during diabetes. This study deepens our understanding of impaired cardiac function in diabetes, identifies GCH1 as a modulator of cardiac remodeling and function, and reveals a new therapeutic target for diabetic cardiomyopathy.
C1 [Wu, Hsiang-En; Baumgardt, Shelley L.; Paterson, Mark; Qiao, Shigang; Bosnjak, Zeljko J.; Warltier, David C.; Kersten, Judy R.; Ge, Zhi-Dong] Med Coll Wisconsin, Dept Anesthesiol, 8701 Watertown Plank Rd, Milwaukee, WI 53226 USA.
[Wu, Hsiang-En] NIDA, NIH, 251 Bayview Blvd, Baltimore, MD 21224 USA.
[Fang, Juan] Med Coll Wisconsin, Dept Pediat, 8701 Watertown Plank Rd, Milwaukee, WI 53226 USA.
[Liu, Yanan] Columbia Univ, Dept Med, 630 W 168th St, New York, NY 10032 USA.
[Du, Jianhai] Univ Washington, Dept Biochem, 1705 NE Pacific St, Seattle, WA 98195 USA.
[Shi, Yang] Aurora Hlth Care, Aurora Res Inst, 750 W Virginia St, Milwaukee, WI 53234 USA.
[Bosnjak, Zeljko J.] Med Coll Wisconsin, Dept Physiol, 8701 Watertown Plank Rd, Milwaukee, WI 53226 USA.
[Warltier, David C.; Kersten, Judy R.] Med Coll Wisconsin, Dept Pharmacol & Toxicol, 8701 Watertown Plank Rd, Milwaukee, WI 53226 USA.
RP Ge, ZD (reprint author), Med Coll Wisconsin, Dept Anesthesiol, 8701 Watertown Plank Rd, Milwaukee, WI 53226 USA.
EM Wilson.ge99@gmail.com
FU National Institutes of Health [GM 066730]; United States Public Health
Services, Bethesda, Maryland [HL 063705]; Pilot Grant from Research
Affairs Committee, Medical College of Wisconsin
FX We are grateful to Drs. John A. Auchampach, Ph.D. and Tina C. Wan, Ph.D.
(Department of Pharmacology and Toxicology, Medical College of
Wisconsin) for their equipment. This work was supported in part by the
National Institutes of Health research grant GM 066730 and HL 063705
from the United States Public Health Services, Bethesda, Maryland and
the Pilot Grant from Research Affairs Committee, Medical College of
Wisconsin.
NR 72
TC 1
Z9 1
U1 1
U2 5
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2045-2322
J9 SCI REP-UK
JI Sci Rep
PD JUN 13
PY 2016
VL 6
AR 27925
DI 10.1038/srep27925
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DO3DS
UT WOS:000377661200002
PM 27295516
ER
PT J
AU Baty, H
Nishikawa, H
AF Baty, Hubert
Nishikawa, Hiroaki
TI Hyperbolic method for magnetic reconnection process in steady state
magnetohydrodynamics
SO MONTHLY NOTICES OF THE ROYAL ASTRONOMICAL SOCIETY
LA English
DT Article
DE magnetic reconnection; MHD-methods: numerical; Sun: flares
ID FINITE-VOLUME; 2 DIMENSIONS; DIFFUSION; SCHEMES; ANNIHILATION; ADVECTION
AB A recent numerical approach for solving the advection-diffusion and Navier-Stokes equations is extended for the first time to a magnetohydrodynamic (MHD) model, aiming in particular consistent improvements over classical methods for investigating the magnetic reconnection process. In this study, we mainly focus on a two-dimensional incompressible set of resistive MHD equations written in flux-vorticity scalar variables. The originality of the method is based on hyperbolic reformulation of the dissipative terms, leading to the construction of an equivalent hyperbolic first-order (spatial derivatives) system. This enables the use of approximate Riemann solvers for handling dissipative and advective flux in the same way. A simple second-order finite-volume discretization on rectangular grids using an upwind flux is employed. The advantages of this method are illustrated by a comparison to two particular analytical steady state solutions of the inviscid magnetic reconnection mechanism, namely the magnetic annihilation and the reconnective diffusion problems. In particular, the numerical solution is obtained with the same order of accuracy for the solution and gradient for a wide range of magnetic Reynolds numbers, without any deterioration characteristic of more conventional schemes. The amelioration of the hyperbolic method and its extension to time-dependent MHD problems related to solar flares mechanisms is also discussed.
C1 [Baty, Hubert] Univ Strasbourg, Observ Astronom Strasbourg, CNRS, UMR 7550, F-67000 Strasbourg, France.
[Nishikawa, Hiroaki] NIA, Hampton, VA 23666 USA.
RP Baty, H (reprint author), Univ Strasbourg, Observ Astronom Strasbourg, CNRS, UMR 7550, F-67000 Strasbourg, France.
EM hubert.baty@unistra.fr
RI Nishikawa, Hiroaki/M-1247-2016
OI Nishikawa, Hiroaki/0000-0003-4472-5313
FU French National Research Agency (ANR) [ANR-13-JS05-0003-01]
FX The authors thank P. Helluy, J. Petri, and P. Ackerer for fruitful
discussions. HB acknowledges support by French National Research Agency
(ANR) through Grant ANR-13-JS05-0003-01 (Project EMPERE). We also
acknowledge computational facilities available at Equip@Meso of the
Universite de Strasbourg. We sincerely thank the anonymous referee for
useful suggestions that helped improve the content of the paper.
NR 25
TC 0
Z9 0
U1 0
U2 1
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0035-8711
EI 1365-2966
J9 MON NOT R ASTRON SOC
JI Mon. Not. Roy. Astron. Soc.
PD JUN 11
PY 2016
VL 459
IS 1
BP 624
EP 637
DI 10.1093/mnras/stw654
PG 14
WC Astronomy & Astrophysics
SC Astronomy & Astrophysics
GA DM5KB
UT WOS:000376386600049
ER
PT J
AU Blauwendraat, C
Francescatto, M
Gibbs, JR
Jansen, IE
Simon-Sanchez, J
Hernandez, DG
Dillman, AA
Singleton, AB
Cookson, MR
Rizzu, P
Heutink, P
AF Blauwendraat, Cornelis
Francescatto, Margherita
Gibbs, J. Raphael
Jansen, Iris E.
Simon-Sanchez, Javier
Hernandez, Dena G.
Dillman, Allissa A.
Singleton, Andrew B.
Cookson, Mark R.
Rizzu, Patrizia
Heutink, Peter
TI Comprehensive promoter level expression quantitative trait loci analysis
of the human frontal lobe
SO GENOME MEDICINE
LA English
DT Article
DE Expression quantitative trait loci (eQTL); frontal lobe cortex; NRGN;
Cap analysis gene expression sequencing (CAGEseq); PARK16
ID GENOME-WIDE ASSOCIATION; 17Q21.31 MICRODELETION SYNDROME; ANALYSIS
GENE-EXPRESSION; LONG NONCODING RNAS; DNA-SEQUENCING DATA;
PARKINSONS-DISEASE; CAP-ANALYSIS; TISSUE EXPRESSION; COMMON VARIANTS;
KANSL1 CAUSE
AB Background: Expression quantitative trait loci (eQTL) analysis is a powerful method to detect correlations between gene expression and genomic variants and is widely used to interpret the biological mechanism underlying identified genome wide association studies (GWAS) risk loci. Numerous eQTL studies have been performed on different cell types and tissues of which the majority has been based on microarray technology.
Methods: We present here an eQTL analysis based on cap analysis gene expression sequencing (CAGEseq) data created from human postmortem frontal lobe tissue combined with genotypes obtained through genotyping arrays, exome sequencing, and CAGEseq. Using CAGEseq as an expression profiling technique combined with these different genotyping techniques allows measurement of the molecular effect of variants on individual transcription start sites and increases the resolution of eQTL analysis by also including the non-annotated parts of the genome.
Results: We identified 2410 eQTLs and show that non-coding transcripts are more likely to contain an eQTL than coding transcripts, in particular antisense transcripts. We provide evidence for how previously identified GWAS loci for schizophrenia (NRGN), Parkinson's disease, and Alzheimer's disease (PARK16 and MAPT loci) could increase the risk for disease at a molecular level. Furthermore, we demonstrate that CAGEseq improves eQTL analysis because variants obtained from CAGEseq are highly enriched for having a functional effect and thus are an efficient method towards the identification of causal variants.
Conclusion: Our data contain both coding and non-coding transcripts and has the added value that we have identified eQTLs for variants directly adjacent to TSS. Future eQTL studies would benefit from combining CAGEseq with RNA sequencing for a more complete interpretation of the transcriptome and increased understanding of eQTL signals.
C1 [Blauwendraat, Cornelis; Rizzu, Patrizia] German Ctr Neurodegenerat Dis DZNE, Appl Genom Neurodegenerat Dis, Tubingen, Germany.
[Francescatto, Margherita; Jansen, Iris E.; Simon-Sanchez, Javier; Heutink, Peter] German Ctr Neurodegenerat Dis DZNE, Genome Biol Neurodegenerat Dis, Tubingen, Germany.
[Gibbs, J. Raphael; Hernandez, Dena G.; Dillman, Allissa A.; Singleton, Andrew B.; Cookson, Mark R.] NIA, Lab Neurogenet, Bethesda, MD 20892 USA.
[Gibbs, J. Raphael] UCL, Inst Neurol, Dept Mol Neurosci, London, England.
[Jansen, Iris E.; Heutink, Peter] Vrije Univ Amsterdam Med Ctr, Dept Clin Genet, Amsterdam, Netherlands.
[Simon-Sanchez, Javier; Heutink, Peter] Univ Tubingen, Hertie Inst Clin Brain Res, Dept Neurodegenerat Dis, Tubingen, Germany.
RP Blauwendraat, C (reprint author), German Ctr Neurodegenerat Dis DZNE, Appl Genom Neurodegenerat Dis, Tubingen, Germany.
EM cornelis.blauwendraat@gmail.com
FU European Union Seventh Framework Program [FP7-People-ITN-2008-238055];
EU Joint Program-Neurodegenerative Diseases (JPND); RiMod-FTD;
Intramural Research Program of the NIH, National Institute on Aging
[AG000932, AG000947]
FX The research leading to these results has received funding from the
European Union Seventh Framework Program under grant agreement
FP7-People-ITN-2008-238055 ("BrainTrain" project) and the EU Joint
Program-Neurodegenerative Diseases (JPND); RiMod-FTD. This research was
supported in part by the Intramural Research Program of the NIH,
National Institute on Aging (Project numbers AG000932 and AG000947).
NR 90
TC 0
Z9 0
U1 8
U2 8
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1756-994X
J9 GENOME MED
JI Genome Med.
PD JUN 10
PY 2016
VL 8
AR 65
DI 10.1186/s13073-016-0320-1
PG 15
WC Genetics & Heredity
SC Genetics & Heredity
GA DP6FM
UT WOS:000378592300002
PM 27287230
ER
PT J
AU Kim, S
Thiessen, PA
Cheng, T
Yu, B
Shoemaker, BA
Wang, JY
Bolton, EE
Wang, YL
Bryant, SH
AF Kim, Sunghwan
Thiessen, Paul A.
Cheng, Tiejun
Yu, Bo
Shoemaker, Benjamin A.
Wang, Jiyao
Bolton, Evan E.
Wang, Yanli
Bryant, Stephen H.
TI Literature information in PubChem: associations between PubChem records
and scientific articles
SO JOURNAL OF CHEMINFORMATICS
LA English
DT Article
ID SMALL MOLECULES; DATABASE; UPDATE; COLLECTION; ACCESS; SYSTEM; ENTREZ
AB Background: PubChem is an open archive consisting of a set of three primary public databases (BioAssay, Compound, and Substance). It contains information on a broad range of chemical entities, including small molecules, lipids, carbohydrates, and (chemically modified) amino acid and nucleic acid sequences (including siRNA and miRNA). Currently (as of Nov. 2015), PubChem contains more than 150 million depositor-provided chemical substance descriptions, 60 million unique chemical structures, and 225 million biological activity test results provided from over 1 million biological assay records.
Description: Many PubChem records (substances, compounds, and assays) include depositor-provided cross-references to scientific articles in PubMed. Some PubChem contributors provide bioactivity data extracted from scientific articles. Literature-derived bioactivity data complement high-throughput screening (HTS) data from the concluded NIH Molecular Libraries Program and other HTS projects. Some journals provide PubChem with information on chemicals that appear in their newly published articles, enabling concurrent publication of scientific articles in journals and associated data in public databases. In addition, PubChem links records to PubMed articles indexed with the Medical Subject Heading (MeSH) controlled vocabulary thesaurus.
Conclusion: Literature information, both provided by depositors and derived from MeSH annotations, can be accessed using PubChem's web interfaces, enabling users to explore information available in literature related to PubChem records beyond typical web search results.
C1 [Kim, Sunghwan; Thiessen, Paul A.; Cheng, Tiejun; Yu, Bo; Shoemaker, Benjamin A.; Wang, Jiyao; Bolton, Evan E.; Wang, Yanli; Bryant, Stephen H.] Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Dept Hlth & Human Serv, 8600 Rockville Pike, Bethesda, MD 20894 USA.
RP Kim, S (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Dept Hlth & Human Serv, 8600 Rockville Pike, Bethesda, MD 20894 USA.
EM kimsungh@ncbi.nlm.nih.gov
RI Kim, Sunghwan/A-6738-2008
OI Kim, Sunghwan/0000-0001-9828-2074
FU Intramural Research Program of the National Library of Medicine,
National Institutes of Health
FX This work was supported by the Intramural Research Program of the
National Library of Medicine, National Institutes of Health. Special
thanks to PubChem team members (present and past), the Entrez
infrastructure group, the MeSH group, and all PubChem data contributors
without which this work would not be possible. We also thank Nancy
Terry, NIH Library Editing Service, for reviewing the manuscript.
NR 26
TC 1
Z9 1
U1 1
U2 5
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1758-2946
J9 J CHEMINFORMATICS
JI J. Cheminformatics
PD JUN 10
PY 2016
VL 8
AR 32
DI 10.1186/s13321-016-0142-6
PG 15
WC Chemistry, Multidisciplinary; Computer Science, Information Systems;
Computer Science, Interdisciplinary Applications
SC Chemistry; Computer Science
GA DP0UH
UT WOS:000378204900001
PM 27293485
ER
PT J
AU Loell, I
Raouf, J
Chen, YW
Shi, RY
Nennesmo, I
Alexanderson, H
Dastmalchi, M
Nagaraju, K
Korotkova, M
Lundberg, IE
AF Loell, Ingela
Raouf, Joan
Chen, Yi-Wen
Shi, Rongye
Nennesmo, Inger
Alexanderson, Helene
Dastmalchi, Maryam
Nagaraju, Kanneboyina
Korotkova, Marina
Lundberg, Ingrid E.
TI Effects on muscle tissue remodeling and lipid metabolism in muscle
tissue from adult patients with polymyositis or dermatomyositis treated
with immunosuppressive agents
SO ARTHRITIS RESEARCH & THERAPY
LA English
DT Article
DE Glucocorticoids; Treatment; Muscle biopsies; Polymyositis;
Dermatomyositis; Gene expression profiling
ID IDIOPATHIC INFLAMMATORY MYOPATHIES; INDUCIBLE GENE-EXPRESSION; I
INTERFERON; MUSCULAR-DYSTROPHIES; INSULIN-RESISTANCE; DISEASE-ACTIVITY;
RECEPTOR; FIBERS; GLUCOCORTICOIDS; LIPODYSTROPHY
AB Background: Polymyositis (PM) and dermatomyositis (DM) are autoimmune muscle diseases, conventionally treated with high doses of glucocorticoids in combination with immunosuppressive drugs. Treatment is often dissatisfying, with persisting muscle impairment. We aimed to investigate molecular mechanisms that might contribute to the persisting muscle impairment despite immunosuppressive treatment in adult patients with PM or DM using gene expression profiling of repeated muscle biopsies.
Methods: Paired skeletal muscle biopsies from six newly diagnosed adult patients with DM or PM taken before and after conventional immunosuppressive treatment were examined by gene expression microarray analysis. Selected genes that displayed changes in expression were analyzed by Western blot. Muscle biopsy sections were evaluated for inflammation, T lymphocytes (CD3), macrophages (CD68), major histocompatibility complex (MHC) class I expression and fiber type composition.
Results: After treatment, genes related to immune response and inflammation, including inflammasome pathways and interferon, were downregulated. This was confirmed at the protein level for AIM-2 and caspase-1 in the inflammasome pathway. Changes in genes involved in muscle tissue remodeling suggested a negative effect on muscle regeneration and growth. Gene markers for fast type II fibers were upregulated and fiber composition was switched towards type II fibers in response to treatment. The expression of genes involved in lipid metabolism was altered, suggesting a potential lipotoxic effect on muscles of the immunosuppressive treatment.
Conclusion: The anti-inflammatory effect of immunosuppressive treatment was combined with negative effects on genes involved in muscle tissue remodeling and lipid metabolism, suggesting a negative effect on recovery of muscle performance which may contribute to persisting muscle impairment in adult patients with DM and PM.
C1 [Loell, Ingela; Raouf, Joan; Dastmalchi, Maryam; Korotkova, Marina; Lundberg, Ingrid E.] Karolinska Univ Hosp Solna, Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden.
[Chen, Yi-Wen; Nagaraju, Kanneboyina] Med Genet Res Ctr, Childrens Natl Med Ctr, Washington, DC USA.
[Shi, Rongye] NHLBI, Ctr Human Immunol Autoimmun & Inflammat, NIH, Bldg 10, Bethesda, MD 20892 USA.
[Nennesmo, Inger] Karolinska Univ Hosp Huddinge, Inst Lab Med LABMED, Stockholm, Sweden.
[Alexanderson, Helene] Karolinska Inst, Dept NVS, Div Phys Therapy, Stockholm, Sweden.
[Alexanderson, Helene] Karolinska Univ Hosp Solna, Phys Therapy Clin, Stockholm, Sweden.
RP Lundberg, IE (reprint author), Karolinska Univ Hosp Solna, Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden.
EM Ingrid.Lundberg@ki.se
FU Swedish Research Council; Swedish Rheumatism Association; King Gustaf V
80 Year Foundation; Karolinska Institutet; Stockholm County Council;
National Institutes of Health [K26OD011171, R24HD050846-02,
P50AR060836]; United States Department of Defense [W81XWH-05-1-0659,
W81XWH-11-1-0782, W81XWH-11-1-0330, W81XWH 10-1-0767]
FX This study was supported by grants from the Swedish Research Council,
the Swedish Rheumatism Association, King Gustaf V 80 Year Foundation,
Funds at the Karolinska Institutet and through the regional agreement on
medical training and clinical research (ALF) between Stockholm County
Council and Karolinska Institutet. KN was supported by National
Institutes of Health grantss K26OD011171, R24HD050846-02, and
P50AR060836, and United States Department of Defense grants
W81XWH-05-1-0659, W81XWH-11-1-0782, W81XWH-11-1-0330, and W81XWH
10-1-0767.
NR 44
TC 1
Z9 1
U1 1
U2 3
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1478-6354
EI 1478-6362
J9 ARTHRITIS RES THER
JI Arthritis Res. Ther.
PD JUN 10
PY 2016
VL 18
AR 136
DI 10.1186/s13075-016-1033-y
PG 13
WC Rheumatology
SC Rheumatology
GA DO7QK
UT WOS:000377976900002
PM 27287443
ER
PT J
AU Gillies, CE
Otto, EA
Vega-Warner, V
Robertson, CC
Sanna-Cherchi, S
Gharavi, A
Crawford, B
Bhimma, R
Winkler, C
Kang, HM
Sampson, MG
AF Gillies, Christopher E.
Otto, Edgar A.
Vega-Warner, Virginia
Robertson, Catherine C.
Sanna-Cherchi, Simone
Gharavi, Ali
Crawford, Brendan
Bhimma, Rajendra
Winkler, Cheryl
Kang, Hyun Min
Sampson, Matthew G.
CA Nephrotic Syndrome Study Network
Michigan Kidney Translational Core
TI tarSVM: Improving the accuracy of variant calls derived from
microfluidic PCR-based targeted next generation sequencing using a
support vector machine
SO BMC BIOINFORMATICS
LA English
DT Article
DE Microfluidic; PCR; Next-generation sequencing; Variant calling;
Accuracy; Support vector machine; Nephrotic
ID NEPHROTIC SYNDROME; NEPHROPATHY; CILIOPATHY; MUTATIONS; FRAMEWORK;
GENOMES
AB Background: Targeted sequencing of discrete gene sets is a cost effective strategy to screen subjects for monogenic forms of disease. One method to achieve this pairs microfluidic PCR with next generation sequencing. The PCR step of this pipeline creates challenges in accurate variant calling. This includes that most reads targeting a specific exon are duplicates that have been amplified from the PCR step. To reduce false positive variant calls from these experiments, previous studies have used threshold-based filtering of alternative allele depth ratio and manual inspection of the alignments. However even after manual inspection and filtering, many variants fail to be validated via Sanger sequencing. To improve the accuracy of variant calling from these experiments, we are challenged to design a variant filtering strategy that sufficiently models microfluidic PCR-specific issues.
Results: We developed an open source variant filtering pipeline, targeted sequencing support vector machine ("tarSVM"), that uses a Support Vector Machine (SVM) and a new score the normalized allele dosage test to identify high quality variants from microfluidic PCR data. tarSVM maximizes training knowledge by selecting variants that are likely true and likely false variants by incorporating knowledge from the 1000 Genomes and the Exome Aggregation Consortium projects. tarSVM improves on previous approaches by synthesizing variant features from the Genome Analysis Toolkit and allele dosage information. We compared the accuracy of tarSVM versus existing variant quality filtering strategies on two cohorts (n = 474 and n = 1152), and validated our method on a third cohort (n = 75). In the first cohort, our method achieved 84.5 % accuracy of predicting whether or not a variant would be validated with Sanger sequencing versus 78.8 % for the second most accurate method. In the second cohort, our method had an accuracy of 73.3 %, versus 61.5 % for the second best method. Finally, our method had a false discovery rate of 5 % for the validation cohort.
Conclusions: tarSVM increases the accuracy of variant calling when using microfluidic PCR based targeted sequencing approaches. This results in higher confidence downstream analyses, and ultimately reduces the costs Sanger validation. Our approach is less labor intensive than existing approaches, and is available as an open source pipeline for read trimming, aligning, variant calling, and variant quality filtering on GitHub at https://github.com/christopher-gillies/TargetSpecificGATKSequencingPipeline.
C1 [Gillies, Christopher E.; Vega-Warner, Virginia; Robertson, Catherine C.; Crawford, Brendan; Sampson, Matthew G.] Univ Michigan, Sch Med, Dept Pediat Nephrol, Ann Arbor, MI USA.
[Otto, Edgar A.] Univ Michigan, Sch Med, Dept Internal Med Nephrol, Ann Arbor, MI USA.
[Sanna-Cherchi, Simone; Gharavi, Ali] Columbia Univ, Dept Med, Coll Phys & Surg, New York, NY USA.
[Bhimma, Rajendra] Univ KwaZulu Natal, Dept Paediat & Child Hlth, Durban, South Africa.
[Winkler, Cheryl] NCI, Frederick Natl Lab Canc Res, Mol Genet Epidemiol Sect, Frederick, MD 21701 USA.
[Kang, Hyun Min] Univ Michigan, Sch Publ Hlth, Dept Biostat, Ann Arbor, MI 48109 USA.
[Sampson, Matthew G.] 3560B MSRB2,1150 West Med Ctr Dr, Ann Arbor, MI 48109 USA.
RP Sampson, MG (reprint author), Univ Michigan, Sch Med, Dept Pediat Nephrol, Ann Arbor, MI USA.; Sampson, MG (reprint author), 3560B MSRB2,1150 West Med Ctr Dr, Ann Arbor, MI 48109 USA.
EM mgsamps@med.umich.edu
OI Otto, Edgar/0000-0002-2387-9973
FU University of Michigan; NephCure Kidney International; Halpin
Foundation; National Cancer Institute, National Institutes of Health
[HHSN26120080001E]; Intramural Research Program of the NIH, National
Cancer Institute, Center for Cancer Research; NIDDK [1 K08-DK100662-01];
Office of Rare Diseases Research (ORDR), NCATS [U54-DK-083912]; National
Institute of Diabetes, Digestive, and Kidney Diseases [U54-DK-083912]
FX The Nephrotic Syndrome Study Network Consortium (NEPTUNE);
U54-DK-083912, is a part of the National Center for Advancing
Translational Sciences (NCATS) Rare Disease Clinical Research Network
(RDCRN), supported through a collaboration between the Office of Rare
Diseases Research (ORDR), NCATS, and the National Institute of Diabetes,
Digestive, and Kidney Diseases. RDCRN is an initiative of ORDR, NCATS.
Additional funding and/or programmatic support for this project has also
been provided by the University of Michigan, NephCure Kidney
International, and the Halpin Foundation.; This project has been funded
in part with federal funds from the National Cancer Institute, National
Institutes of Health, under contract HHSN26120080001E. The content of
this publication does not necessarily reflect the views or policies of
the Department of Health and Human Services, nor does mention of trade
names, commercial products, or organizations imply endorsement by the
U.S. Government. This Research was supported in part by the Intramural
Research Program of the NIH, National Cancer Institute, Center for
Cancer Research.; M.G.S. is a Carl Gottschalk Research Scholar of the
American Society of Nephrology and is supported by the NIDDK Grant 1
K08-DK100662-01.
NR 22
TC 0
Z9 0
U1 1
U2 3
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2105
J9 BMC BIOINFORMATICS
JI BMC Bioinformatics
PD JUN 10
PY 2016
VL 17
AR 233
DI 10.1186/s12859-016-1108-4
PG 13
WC Biochemical Research Methods; Biotechnology & Applied Microbiology;
Mathematical & Computational Biology
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Mathematical & Computational Biology
GA DO5XU
UT WOS:000377857200001
PM 27287006
ER
PT J
AU Godfrey, C
Tauscher, G
Hunsberger, S
Austin, M
Scott, L
Schouten, JT
Luetkemeyer, AF
Benson, C
Coombs, R
Swindells, S
AF Godfrey, Catherine
Tauscher, Gail
Hunsberger, Sally
Austin, Melissa
Scott, Lesley
Schouten, Jeffrey T.
Luetkemeyer, Anne F.
Benson, Constance
Coombs, Robert
Swindells, Susan
CA HIV Network Coordinating HANC TB D
Natl Inst Allergy Infect Dis
TI A survey of tuberculosis infection control practices at the
NIH/NIAID/DAIDS-supported clinical trial sites in low and middle income
countries
SO BMC INFECTIOUS DISEASES
LA English
DT Article
DE Infection prevention; HIV; AIDS; Resource limited; IC; Tuberculosis;
Tuberculosis prevention; Low and middle income countries
ID HEALTH-CARE WORKERS; DRUG-RESISTANT TUBERCULOSIS; SOUTH-AFRICA;
HOSPITALS; SETTINGS; NIGERIA; RISK
AB Background: Health care associated transmission of Mycobacterium tuberculosis (TB) is well described. A previous survey of infection control (IC) practices at clinical research sites in low and middle income countries (LMIC) funded by the National Institute of Allergy and Infectious Diseases (NIAID) conducting HIV research identified issues with respiratory IC practices. A guideline for TB IC based on international recommendations was developed and promulgated. This paper reports on adherence to the guideline at sites conducting or planning to conduct TB studies with the intention of supporting improvement.
Methods: A survey was developed that assessed IC activities in three domains: facility level measures, administrative control measures and environmental measures. An external site monitor visited each site in 2013-2014, to complete the audit. A central review committee evaluated the site-level survey and results were tabulated. Fisher's exact test was performed to determine whether there were significant differences in practices at sites that had IC officers versus sites that did not have IC officers. Significance was assessed at p=.05
Results: Seven of thirty-three sites surveyed (22 %) had all the evaluated tuberculosis IC (TB IC) elements in place. Sixty-one percent of sites had an IC officer tasked with developing and maintaining TB IC standard operating procedures. Twenty-two (71 %) sites promptly identified and segregated individuals with TB symptoms. Thirty (93 %) sites had a separate waiting area for patients, and 26 (81 %) collected sputum within a specific well-ventilated area that was separate from the general waiting area. Sites with an IC officer were more likely to have standard operating procedures covering TB IC practices (p = 0.02) and monitor those policies (p = 0.02) and perform regular surveillance of healthcare workers (p = 0.02). The presence of an IC officer had a positive impact on performance in most of the TB IC domains surveyed including having adequate ventilation (p = 0.02) and a separate area for sputum collection (p = 0.02)
Conclusions: Specific and targeted support of TB IC activities in the clinical research environment is needed and is likely to have a positive and sustained impact on preventing the transmission of TB to both health care workers and vulnerable HIV-infected research participants.
C1 [Godfrey, Catherine; Tauscher, Gail; Hunsberger, Sally] NIAID, Div Aids, 5601 Fishers Lane Room 9E49,MSC 9830, Bethesda, MD 20892 USA.
[Austin, Melissa; Schouten, Jeffrey T.] Off HIV AIDS Network Coordinat, Seattle, WA USA.
[Scott, Lesley] Univ Witwatersrand, Fac Hlth Sci, Dept Mol Med & Haematol, Sch Pathol, Johannesburg, South Africa.
[Austin, Melissa; Schouten, Jeffrey T.] Fred Hutchinson Canc Res Ctr, 1124 Columbia St, Seattle, WA 98104 USA.
[Luetkemeyer, Anne F.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Benson, Constance] Univ Calif San Diego, San Diego, CA 92103 USA.
[Coombs, Robert] Univ Washington, Dept Lab Med, Seattle, WA 98195 USA.
[Coombs, Robert] Univ Washington, Dept Med, Seattle, WA USA.
[Swindells, Susan] Univ Nebraska Med Ctr, Dept Med, Omaha, NE USA.
RP Godfrey, C (reprint author), NIAID, Div Aids, 5601 Fishers Lane Room 9E49,MSC 9830, Bethesda, MD 20892 USA.
EM cgodfrey@niaid.nih.gov
FU National Institute of Allergy and Infectious Diseases [UM1-AI-068636,
UM1-AI-106701]; National Institute of Mental Health (NIMH), National
Institute of Dental and Craniofacial Research (NIDCR)
FX The project described was supported by Award Number UM1-AI-068636;
UM1-AI-106701 from the National Institute of Allergy and Infectious
Diseases and supported by National Institute of Mental Health (NIMH),
National Institute of Dental and Craniofacial Research (NIDCR). The
content is solely the responsibility of the authors and does not
necessarily represent the official views of the National Institute of
Allergy and Infectious Diseases or the National Institutes of Health.
NR 31
TC 2
Z9 2
U1 1
U2 3
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2334
J9 BMC INFECT DIS
JI BMC Infect. Dis.
PD JUN 10
PY 2016
VL 16
AR 269
DI 10.1186/s12879-016-1579-y
PG 7
WC Infectious Diseases
SC Infectious Diseases
GA DO7ET
UT WOS:000377945900001
PM 27287374
ER
PT J
AU Ebert, RF
Danthi, NS
Charette, MF
Hanspal, M
Mondoro, TH
Noel, PJ
Olive, M
Punturieri, A
Moore, TM
AF Ebert, Ray F.
Danthi, Narasimhan S.
Charette, Marc F.
Hanspal, Manjit
Mondoro, Traci H.
Noel, Patricia J.
Olive, Michelle
Punturieri, Antonello
Moore, Timothy M.
TI The NHLBI SMARTT Program A Novel Approach to Facilitate Translational
Research for Heart, Lung and Blood Diseases
SO CIRCULATION RESEARCH
LA English
DT Article
DE blood; heart; lung; sleep wake disorders; translational research
AB The National Heart, Lung, and Blood Institute (NHLBI), one of 27 institutes/centers within the National Institutes of Health, has a strong interest in promoting translational research. This can be traced to its mission statement, which reads in part: "The National Heart, Lung, and Blood Institute stimulates basic discoveries about the causes of disease, enables the translation of basic discoveries into clinical practice, fosters training and mentoring of emerging scientists and physicians, and communicates research advances to the public" (http://www.nhlbi.gov/about/org/mission). Each year, the NHLBI invests more than $3 billion to support research, training, and education programs to promote the prevention and treatment of heart, lung, and blood diseases and sleep disorders. More than two thirds of this investment is allocated to investigator-initiated research, spanning the continuum from discovery through preclinical and clinical studies.
C1 [Ebert, Ray F.; Danthi, Narasimhan S.; Charette, Marc F.; Olive, Michelle] NHLBI, Div Cardiovasc Sci, NIH, 6701 Rockledge Dr,Suite 8030, Bethesda, MD 20892 USA.
[Hanspal, Manjit; Mondoro, Traci H.] NHLBI, Div Blood Dis & Resources, NIH, 6701 Rockledge Dr,Suite 8030, Bethesda, MD 20892 USA.
[Noel, Patricia J.; Punturieri, Antonello; Moore, Timothy M.] NHLBI, Div Lung Dis, NIH, 6701 Rockledge Dr,Suite 8030, Bethesda, MD 20892 USA.
RP Ebert, RF (reprint author), NHLBI, Div Cardiovasc Sci, NIH, 6701 Rockledge Dr,Suite 8030, Bethesda, MD 20892 USA.
EM Ray.Ebert@nih.gov
FU Intramural NIH HHS [Z99 HL999999]
NR 1
TC 0
Z9 0
U1 2
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0009-7330
EI 1524-4571
J9 CIRC RES
JI Circ.Res.
PD JUN 10
PY 2016
VL 118
IS 12
BP 1867
EP +
DI 10.1161/CIRCRESAHA.116.308550
PG 7
WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular
Disease
SC Cardiovascular System & Cardiology; Hematology
GA DO6HX
UT WOS:000377885100006
PM 27283530
ER
PT J
AU Kabir, F
Ullah, I
Ali, S
Gottsch, ADH
Naeem, MA
Assir, MZ
Khan, SN
Akram, J
Riazuddin, S
Ayyagari, R
Hejtmancik, JF
Riazuddin, SA
AF Kabir, Firoz
Ullah, Inayat
Ali, Shahbaz
Gottsch, Alexander D. H.
Naeem, Muhammad Asif
Assir, Muhammad Zaman
Khan, Shaheen N.
Akram, Javed
Riazuddin, Sheikh
Ayyagari, Radha
Hejtmancik, J. Fielding
Riazuddin, S. Amer
TI Loss of function mutations in RP1 are responsible for retinitis
pigmentosa in consanguineous familial cases
SO MOLECULAR VISION
LA English
DT Article
ID AUTOSOMAL-RECESSIVE RETINITIS; HOMOZYGOUS MISSENSE MUTATION; ROD CGMP
PHOSPHODIESTERASE; SPLICING FACTOR; RETINAL DYSTROPHY; TRUNCATION
MUTATIONS; NONSENSE MUTATION; DOMINANT MUTATION; GENETIC-ANALYSIS;
BINDING-PROTEIN
AB Purpose: This study was undertaken to identify causal mutations responsible for autosomal recessive retinitis pigmentosa (arRP) in consanguineous families.
Methods: Large consanguineous families were ascertained from the Punjab province of Pakistan. An ophthalmic examination consisting of a fundus evaluation and electroretinography (ERG) was completed, and small aliquots of blood were collected from all participating individuals. Genomic DNA was extracted from white blood cells, and a genome-wide linkage or a locus-specific exclusion analysis was completed with polymorphic short tandem repeats (STRs). Two-point logarithm of odds (LOD) scores were calculated, and all coding exons and exon-intron boundaries of RP1 were sequenced to identify the causal mutation.
Results: The ophthalmic examination showed that affected individuals in all families manifest cardinal symptoms of RP. Genome-wide scans localized the disease phenotype to chromosome 8q, a region harboring RP1, a gene previously implicated in the pathogenesis of RP. Sanger sequencing identified a homozygous single base deletion in exon 4: c.3697delT (p.S1233Pfs22*), a single base substitution in intron 3: c.787+ 1G>A (p.I263Nfs8*), a 2 bp duplication in exon 2: c.551_552dupTA (p.Q185Yfs4*) and an 11,117 bp deletion that removes all three coding exons of RP1. These variations segregated with the disease phenotype within the respective families and were not present in ethnically matched control samples.
Conclusions: These results strongly suggest that these mutations in RP1 are responsible for the retinal phenotype in affected individuals of all four consanguineous families.
C1 [Kabir, Firoz; Gottsch, Alexander D. H.; Riazuddin, S. Amer] Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Baltimore, MD 21287 USA.
[Ullah, Inayat; Ali, Shahbaz; Naeem, Muhammad Asif; Khan, Shaheen N.; Riazuddin, Sheikh] Univ Punjab, Natl Ctr Excellence Mol Biol, Lahore, Pakistan.
[Assir, Muhammad Zaman; Akram, Javed; Riazuddin, Sheikh] Univ Hlth Sci, Allama Iqbal Med Coll, Lahore, Pakistan.
[Assir, Muhammad Zaman; Akram, Javed; Riazuddin, Sheikh] Shaheed Zulfiqar Ali Bhutto Med Univ, Natl Ctr Genet Dis, Islamabad, Pakistan.
[Ayyagari, Radha] Univ Calif San Diego, Shiley Eye Inst, San Diego, CA 92103 USA.
[Hejtmancik, J. Fielding] NEI, Ophthalm Genet & Visual Funct Branch, NIH, Bethesda, MD 20892 USA.
RP Riazuddin, SA (reprint author), Johns Hopkins Univ, Sch Med, 600 N Wolfe St,Maumenee 840, Baltimore, MD 21287 USA.
EM riazuddin@jhmi.edu
FU Higher Education Commission, Islamabad, Pakistan; National Eye Institute
[R01EY021237]
FX We are thankful to all family members for their participation in this
study. This study was supported in part by Higher Education Commission,
Islamabad, Pakistan, and by the National Eye Institute Grant R01EY021237
(RA and SAR).
NR 113
TC 0
Z9 0
U1 2
U2 2
PU MOLECULAR VISION
PI ATLANTA
PA C/O JEFF BOATRIGHT, LAB B, 5500 EMORY EYE CENTER, 1327 CLIFTON RD, N E,
ATLANTA, GA 30322 USA
SN 1090-0535
J9 MOL VIS
JI Mol. Vis.
PD JUN 10
PY 2016
VL 22
BP 610
EP 625
PG 16
WC Biochemistry & Molecular Biology; Ophthalmology
SC Biochemistry & Molecular Biology; Ophthalmology
GA DO6YX
UT WOS:000377930500001
PM 27307693
ER
PT J
AU Lemley, KV
Bagnasco, SM
Nast, CC
Barisoni, L
Conway, CM
Hewitt, SM
Song, PXK
AF Lemley, Kevin V.
Bagnasco, Serena M.
Nast, Cynthia C.
Barisoni, Laura
Conway, Catherine M.
Hewitt, Stephen M.
Song, Peter X. K.
TI Morphometry Predicts Early GFR Change in Primary Proteinuric
Glomerulopathies: A Longitudinal Cohort Study Using Generalized
Estimating Equations
SO PLOS ONE
LA English
DT Article
ID CHRONIC KIDNEY-DISEASE; INTERSTITIAL FIBROSIS; GLOMERULAR DENSITY;
NEPHROTIC SYNDROME; NETWORK NEPTUNE; IGA NEPHROPATHY; PROGRESSION;
BIOPSIES; NUMBER
AB Objective
Most predictive models of kidney disease progression have not incorporated structural data. If structural variables have been used in models, they have generally been only semi-quantitative.
Methods
We examined the predictive utility of quantitative structural parameters measured on the digital images of baseline kidney biopsies from the NEPTUNE study of primary proteinuric glomerulopathies. These variables were included in longitudinal statistical models predicting the change in estimated glomerular filtration rate (eGFR) over up to 55 months of follow-up.
Results
The participants were fifty-six pediatric and adult subjects from the NEPTUNE longitudinal cohort study who had measurements made on their digital biopsy images; 25% were African-American, 70% were male and 39% were children; 25 had focal segmental glomerular sclerosis, 19 had minimal change disease, and 12 had membranous nephropathy. We considered four different sets of candidate predictors, each including four quantitative structural variables (for example, mean glomerular tuft area, cortical density of patent glomeruli and two of the principal components from the correlation matrix of six fractional cortical areas-interstitium, atrophic tubule, intact tubule, blood vessel, sclerotic glomerulus, and patent glomerulus) along with 13 potentially confounding demographic and clinical variables (such as race, age, diagnosis, and baseline eGFR, quantitative proteinuria and BMI). We used longitudinal linear models based on these 17 variables to predict the change in eGFR over up to 55 months. All 4 models had a leave-one-out cross-validated R-2 of about 62%.
Conclusions
Several combinations of quantitative structural variables were significantly and strongly associated with changes in eGFR. The structural variables were generally stronger than any of the confounding variables, other than baseline eGFR. Our findings suggest that quantitative assessment of diagnostic renal biopsies may play a role in estimating the baseline risk of succeeding loss of renal function in future clinical studies, and possibly in clinical practice.
C1 [Lemley, Kevin V.] Univ So Calif, Keck Sch Med, Div Pediat Nephrol, Dept Pediat, Los Angeles, CA 90033 USA.
[Bagnasco, Serena M.] Johns Hopkins Sch Med, Dept Pathol, Baltimore, MD USA.
[Nast, Cynthia C.] Cedars Sinai Med Ctr, Dept Pathol, Los Angeles, CA 90048 USA.
[Barisoni, Laura] Univ Miami, Dept Pathol, Miami, FL USA.
[Conway, Catherine M.; Hewitt, Stephen M.] NCI, NIH, Bethesda, MD 20892 USA.
[Song, Peter X. K.] Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA.
[Conway, Catherine M.] Leica Biosyst Ltd, Dublin, Ireland.
RP Lemley, KV (reprint author), Univ So Calif, Keck Sch Med, Div Pediat Nephrol, Dept Pediat, Los Angeles, CA 90033 USA.
EM klemley@chla.usc.edu
FU NIH/ORDR [U-54DK083912]; NephCure Kidney International; National Cancer
Institute (NIH): Intramural Research
FX This work was supported by NIH/ORDR U-54DK083912; NephCure: nephcure.org
(now NephCure Kidney International); and National Cancer Institute
(NIH): Intramural Research. None of the funders had any role in study
design, data collection or analysis, decision to publish, or preparation
of the manuscript.
NR 20
TC 0
Z9 0
U1 5
U2 5
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUN 10
PY 2016
VL 11
IS 6
AR e0157148
DI 10.1371/journal.pone.0157148
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DO1UG
UT WOS:000377564000040
PM 27285824
ER
PT J
AU Gao, Y
Yang, W
AF Gao, Yang
Yang, Wei
TI Capture of a third Mg2+ is essential for catalyzing DNA synthesis
SO SCIENCE
LA English
DT Article
ID POLYMERASE-ETA; COMPUTATIONAL DESIGN; ENZYME CATALYSIS; INDUCED-FIT;
MECHANISM; NUCLEOTIDE; FIDELITY; POLYMERIZATION; REPLICATION;
SPECIFICITY
AB It is generally assumed that an enzyme-substrate (ES) complex contains all components necessary for catalysis and that conversion to products occurs by rearrangement of atoms, protons, and electrons. However, we find that DNA synthesis does not occur in a fully assembled DNA polymerase-DNA-deoxynucleoside triphosphate complex with two canonical metal ions bound. Using time -resolved x-ray crystallography, we show that the phosphoryltransfer reaction takes place only after the ES complex captures a third divalent cation that is not coordinated by the enzyme. Binding of the third cation is incompatible with the basal ES complex and requires thermal activation of the ES for entry. It is likely that the third cation provides the ultimate boost over the energy barrier to catalysis of DNA synthesis.
C1 [Gao, Yang; Yang, Wei] NIDDK, Mol Biol Lab, Bethesda, MD 20892 USA.
RP Yang, W (reprint author), NIDDK, Mol Biol Lab, Bethesda, MD 20892 USA.
EM wei.yang@nih.gov
RI Gao, Yang/O-3445-2016
FU NIH [DK036146-08]
FX Y.G. carried out all experiments; W.Y. conceived and designed the
project, and both authors interpreted data and prepared the manuscript.
We thank D. J. Leahy and M. Gellert for critical reading and editing the
manuscript. This work is funded by NIH intramural program (DK036146-08,
W.Y.).
NR 32
TC 8
Z9 8
U1 12
U2 22
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 0036-8075
EI 1095-9203
J9 SCIENCE
JI Science
PD JUN 10
PY 2016
VL 352
IS 6291
BP 1334
EP 1337
DI 10.1126/science.aad9633
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DO7ON
UT WOS:000377972000045
PM 27284197
ER
PT J
AU Wang, JJ
Sun, LG
Chen, LQ
Xu, LB
Wang, YH
Wang, XM
AF Wang, Jianjun
Sun, Liguang
Chen, Liqi
Xu, Libin
Wang, Yuhong
Wang, Xinming
TI The abrupt climate change near 4,400 yr BP on the cultural transition in
Yuchisi, China and its global linkage
SO SCIENTIFIC REPORTS
LA English
DT Article
ID LATE HOLOCENE; FATTY-ACIDS; COLLAPSE; DROUGHT; AFRICAN; RECORD;
CIVILIZATION; VARIABILITY; AMERICA; HISTORY
AB Extreme climatic events have profound impacts on human society. Here we present the results of a study of organic biomarkers within a sedimentary section at the archaeological site of Yuchisi, eastern China, in order to reconstruct climatic variability during the Dawenkou (5,050-4,400 yr BP) and Longshan (4,400-4,000 yr BP) cultures. At similar to 4,400 yr BP, within the cultural transition horizon, abrupt changes in biomarkers, such as the fatty acid ratio C-18:2/C-18:0, 2C(31)/(C-27 + C-29), n-C-18-ol and n-C-30-ol, indicate the occurrence of local climate changes over the course of a few decades. These changes occurred during the transition from the Holocene warm period to a subsequent cold period which lasted for the following 600 years. This climatic shift has been recorded at numerous sites worldwide, and it is likely to have been the main cause of the widespread collapse of many isolated cultures at that time. The palaeoclimatic and archaeological data from the Yuchisi sediments may provide new insights into the relationship between climate change and prehistoric cultural transitions.
C1 [Wang, Jianjun; Chen, Liqi] State Ocean Adm, Inst Oceanog 3, Key Lab Global Change & Marine Atmospher Chem, Xiamen, Peoples R China.
[Wang, Jianjun; Sun, Liguang; Xu, Libin] Univ Sci & Technol China, Inst Polar Environm, Hefei 230026, Peoples R China.
[Xu, Libin] Zhangjiagang Water Supply & Drainage Co, Zhangjiagang, Peoples R China.
[Wang, Yuhong] NIH, Bldg 10, Bethesda, MD 20892 USA.
[Wang, Xinming] Chinese Acad Sci, Guangzhou Inst Geochem, Guangzhou, Guangdong, Peoples R China.
RP Wang, JJ (reprint author), State Ocean Adm, Inst Oceanog 3, Key Lab Global Change & Marine Atmospher Chem, Xiamen, Peoples R China.; Wang, JJ; Sun, LG (reprint author), Univ Sci & Technol China, Inst Polar Environm, Hefei 230026, Peoples R China.
EM wangjianjun@tio.org.cn; slg@ustc.edu.cn
FU Scientific Research Foundation of the Third Institute of Oceanography
[2014031]; Ecological Environment Protection Division; State Oceanic
Administration (SOA); Chinese Projects for Investigations and
Assessments of the Arctic and Antarctic [CHINARE 04-03-07]; China
Scholarship Council [201404180008]
FX We thank Prof. Jan Bloemendal, Mr. Iain MacRae and Ms. Mary McPherson
for their language editing of this work. This work was supported by the
Scientific Research Foundation of the Third Institute of Oceanography
(Grant No. 2014031), the Ecological Environment Protection Division, the
State Oceanic Administration (SOA), Chinese Projects for Investigations
and Assessments of the Arctic and Antarctic (CHINARE 04-03-07) and by
the China Scholarship Council (201404180008).
NR 56
TC 0
Z9 0
U1 6
U2 8
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2045-2322
J9 SCI REP-UK
JI Sci Rep
PD JUN 10
PY 2016
VL 6
AR 27723
DI 10.1038/srep27723
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DO3PN
UT WOS:000377693600001
PM 27283832
ER
PT J
AU Ma, HS
Greenblatt, SM
Shirley, CM
Duffield, AS
Bruner, JK
Li, L
Bao, NY
Jung, E
Aplan, PD
Ghiaur, G
Jones, RJ
Small, D
AF Ma, Hayley S.
Greenblatt, Sarah M.
Shirley, Courtney M.
Duffield, Amy S.
Bruner, J. Kyle
Li, Li
Bao Nguyen
Jung, Eric
Aplan, Peter D.
Ghiaur, Gabriel
Jones, Richard J.
Small, Donald
TI All-trans retinoic acid synergizes with FLT3 inhibition to eliminate
FLT3/ITD+ leukemia stem cells in vitro and in vivo
SO BLOOD
LA English
DT Article
ID ACUTE MYELOID-LEUKEMIA; INTERNAL TANDEM DUPLICATION; ACUTE PROMYELOCYTIC
LEUKEMIA; ACUTE MYELOGENOUS LEUKEMIA; PROGNOSTIC-SIGNIFICANCE; KINASE
INHIBITION; MUTATIONS; AML; ATRA; GENE
AB FMS-like tyrosine kinase 3 (FLT3)-mutant acute myeloid leukemia (AML) portends a poor prognosis, and ineffective targeting of the leukemic stem cell (LSC) population remains one of several obstacles in treating this disease. All-trans retinoic acid (ATRA) has been used in several clinical trials for the treatment of nonpromyelocytic AML with limited clinical activity observed. FLT3 tyrosine kinase inhibitors (TKIs) used as monotherapy also achieve limited clinical responses and are thus far unable to affect cure rates in AML patients. We explored the efficacy of combining ATRA and FLT3 TKIs to eliminate FLT3/internal tandem duplication (ITD) 1 LSCs. Our studies reveal highly synergistic drug activity, preferentially inducing apoptosis in FLT3/ITD+ cell lines and patient samples. Colony-forming unit assays further demonstrate decreased clonogenicity of FLT3/ITD+ cells upon treatment with ATRA and TKI. Most importantly, the drug combination depletes FLT3/ITD+ LSCs in a genetic mouse model of AML, and prolongs survival of leukemic mice. Furthermore, engraftment of primary FLT3/ITD+ patient samples is reduced in mice following treatment with FLT3 TKI and ATRA in combination, with evidence of cellular differentiation occurring in vivo. Mechanistically, we provide evidence that the synergism of ATRA and FLT3 TKIs is at least in part due to the observation that FLT3 TKI treatment upregulates the antiapoptotic protein BcI6, limiting the drug's apoptotic effect. However, cotreatment with ATRA reduces BcI6 expression to baseline levels through suppression of interleukin-6 receptor signaling. These studies provide evidence of the potential of this drug combination to eliminate FLT3/ITD+ LSCs and reduce the rate of relapse in AML patients with FLT3 mutations.
C1 [Ma, Hayley S.; Greenblatt, Sarah M.; Shirley, Courtney M.; Bruner, J. Kyle; Li, Li; Bao Nguyen; Ghiaur, Gabriel; Jones, Richard J.; Small, Donald] Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21205 USA.
[Duffield, Amy S.] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA.
[Jung, Eric] Penn State Hershey Coll Med, MD Program, Hershey, PA USA.
[Aplan, Peter D.] NCI, Lab Genet Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Small, Donald] Johns Hopkins Univ, Sch Med, Dept Pediat, Baltimore, MD 21205 USA.
RP Small, D (reprint author), Johns Hopkins, Sidney Kimmel Comprehens Canc Ctr, CRB1,1650 Orleans St, Baltimore, MD 21231 USA.
EM donsmall@jhmi.edu
RI Aplan, Peter/K-9064-2016
FU National Institutes of Health National Cancer Institute [CA90668,
CA006973]; Giant Food Pediatric Cancer Research Fund; Kyle Haydock
Professorship; Rally Foundation (The Truth 365 grant)
FX This work was supported by grants from the National Institutes of Health
National Cancer Institute (CA90668, CA006973), the Rally Foundation (The
Truth 365 grant), and the Giant Food Pediatric Cancer Research Fund.
D.S. is also supported by the Kyle Haydock Professorship.
NR 42
TC 1
Z9 1
U1 0
U2 1
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA
SN 0006-4971
EI 1528-0020
J9 BLOOD
JI Blood
PD JUN 9
PY 2016
VL 127
IS 23
BP 2867
EP 2878
DI 10.1182/blood-2015-05-646786
PG 12
WC Hematology
SC Hematology
GA EC1HV
UT WOS:000387856400001
PM 27103744
ER
PT J
AU Pratt, D
Uldrick, TS
AF Pratt, Drew
Uldrick, Thomas S.
TI Primary effusion lymphoma and concurrent progressive Kaposi sarcoma
associated with elevated interleukin-6
SO BLOOD
LA English
DT Editorial Material
C1 [Pratt, Drew; Uldrick, Thomas S.] NIH, Bldg 10, Bethesda, MD 20892 USA.
RP Pratt, D (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA
SN 0006-4971
EI 1528-0020
J9 BLOOD
JI Blood
PD JUN 9
PY 2016
VL 127
IS 23
BP 2940
EP 2940
DI 10.1182/blood-2016-02-700575
PG 1
WC Hematology
SC Hematology
GA DP2QW
UT WOS:000378335900027
PM 28092896
ER
PT J
AU Solomon, A
Fahey, JL
Malmoren, RA
AF Solomon, Alan
Fahey, John L.
Malmoren, Richard A.
TI Immunohistologic Localization of Gamma-1-Macroglobulins, Beta-2A-Myeloma
Proteins, 6.6 S Gamma-Myeloma Proteins and Bence Jones Proteins.
SO BLOOD
LA English
DT Editorial Material
C1 [Solomon, Alan] NCI, Metab Serv, NIH, Bethesda, MD 20892 USA.
NCI, Pathol Anat Branch, NIH, Bethesda, MD 20892 USA.
RP Solomon, A (reprint author), NCI, Metab Serv, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA
SN 0006-4971
EI 1528-0020
J9 BLOOD
JI Blood
PD JUN 9
PY 2016
VL 127
IS 23
DI 10.1182/blood-2016-04-709774
PG 1
WC Hematology
SC Hematology
GA DP2QW
UT WOS:000378335900002
ER
PT J
AU Sridhar, S
Steele-Mortimer, O
AF Sridhar, Sushmita
Steele-Mortimer, Olivia
TI Inherent Variability of Growth Media Impacts the Ability of Salmonella
Typhimurium to Interact with Host Cells
SO PLOS ONE
LA English
DT Article
ID ENTERICA SEROVAR TYPHIMURIUM; ORGANIC-ACID PRODUCTION; PATHOGENICITY
ISLAND 1; III SECRETION SYSTEMS; D-GLUCARIC ACID; IN-VITRO;
GASTROINTESTINAL-TRACT; EPITHELIAL-CELLS; MAMMALIAN-CELLS; HELA-CELLS
AB Efficient invasion of non-phagocytic cells, such as intestinal epithelial cells, by Salmonella Typhimurium is dependent on the Salmonella Pathogenicity Island 1 (SPI-1)-encoded Type Three Secretion System. The environmental cues involved in SPI-1 induction are not well understood. In vitro, various conditions are used to induce SPI-1 and the invasive phenotype. Although lysogeny broth (LB) is widely used, multiple formulations exist, and variation can arise due to intrinsic differences in complex components. Minimal media are also susceptible to variation. Still, the impact of these inconsistencies on Salmonella virulence gene expression has not been well studied. The goal of this project is to identify growth conditions in LB and minimal mediumthat affect SPI-1 induction in vitro using both whole population and single cell analysis. Here we show, using a fluorescent reporter of the SPI-1 gene prgH, that growth of Salmonella in LB yields variable induction. Deliberate modification of media components can influence the invasive profile. Finally, we demonstrate that changes in SPI-1 inducing conditions can affect the ability of Salmonella to replicate intracellularly. These data indicate that the specific media growth conditions impact how the bacteria interact with host cells.
C1 [Sridhar, Sushmita; Steele-Mortimer, Olivia] NIAID, Bacteriol Lab, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA.
RP Steele-Mortimer, O (reprint author), NIAID, Bacteriol Lab, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA.
EM omortimer@niaid.nih.gov
FU Intramural Research Program of the NIH, NIAID
FX This work is supported by the Intramural Research Program of the NIH,
NIAID. The funders had no role in study design, data collection and
analysis, decision to publish, or preparation of the manuscript.; This
research was supported by the Intramural Research Program of the NIH,
NIAID. We would like to thank Aaron Carmody for expert flow cytometry
support, Anita Mora for figures, and members of the lab for helpful
comments throughout the process.
NR 42
TC 0
Z9 0
U1 3
U2 3
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUN 9
PY 2016
VL 11
IS 6
AR e0157043
DI 10.1371/journal.pone.0157043
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DO1TW
UT WOS:000377563000074
PM 27280414
ER
PT J
AU Brubaker, L
Brown, MB
Weber, AM
AF Brubaker, Linda
Brown, Morton B.
Weber, Anne M.
CA NICHD Pelvic Floor Disorders
TI Corrections to Report of a Trial of Burch Colposuspension
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Letter
C1 [Brubaker, Linda] Loyola Univ, Stritch Sch Med, Chicago, IL 60611 USA.
[Brown, Morton B.] Univ Michigan, Ann Arbor, MI 48109 USA.
[Weber, Anne M.] NIH, Baltimore, MD USA.
RP Brubaker, L (reprint author), Loyola Univ, Stritch Sch Med, Chicago, IL 60611 USA.
EM lbrubaker@luc.edu
NR 1
TC 0
Z9 0
U1 0
U2 0
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
EI 1533-4406
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD JUN 9
PY 2016
VL 374
IS 23
BP 2295
EP 2295
DI 10.1056/NEJMc1605817
PG 1
WC Medicine, General & Internal
SC General & Internal Medicine
GA DO6VB
UT WOS:000377920500026
PM 27276578
ER
PT J
AU Dai, B
Chen, AY
Corkum, CP
Peroutka, RJ
Landon, A
Houng, S
Muniandy, PA
Zhang, Y
Lehrmann, E
Mazan-Mamczarz, K
Steinhardt, J
Shlyak, M
Chen, QC
Becker, KG
Livak, F
Michalak, TI
Talwani, R
Gartenhaus, RB
AF Dai, B.
Chen, A. Y.
Corkum, C. P.
Peroutka, R. J.
Landon, A.
Houng, S.
Muniandy, P. A.
Zhang, Y.
Lehrmann, E.
Mazan-Mamczarz, K.
Steinhardt, J.
Shlyak, M.
Chen, Q. C.
Becker, K. G.
Livak, F.
Michalak, T. I.
Talwani, R.
Gartenhaus, R. B.
TI Hepatitis C virus upregulates B-cell receptor signaling: a novel
mechanism for HCV-associated B-cell lymphoproliferative disorders
SO ONCOGENE
LA English
DT Article
ID BLOOD MONONUCLEAR-CELLS; IN-VIVO; DNA-REPAIR; IONIZING-RADIATION; OCCULT
INFECTION; LOW-LEVEL; EXPRESSION; LYMPHOMA; CHK2; REPLICATION
AB B-cell receptor (BCR) signaling is essential for the development of B cells and has a critical role in B-cell neoplasia. Increasing evidence indicates an association between chronic hepatitis C virus (HCV) infection and B-cell lymphoma, however, the mechanisms by which HCV causes B-cell lymphoproliferative disorder are still unclear. Herein, we demonstrate the expression of HCV viral proteins in B cells of HCV-infected patients and show that HCV upregulates BCR signaling in human primary B cells. HCV nonstructural protein NS3/4A interacts with CHK2 and downregulates its activity, modulating HuR posttranscriptional regulation of a network of target mRNAs associated with B-cell lymphoproliferative disorders. Interestingly, the BCR signaling pathway was found to have the largest number of transcripts with increased association with HuR and was upregulated by NS3/4A. Our study reveals a previously unidentified role of NS3/4A in regulation of host BCR signaling during HCV infection, contributing to a better understanding of the molecular mechanisms underlying HCV-associated B-cell lymphoproliferative disorders.
C1 [Dai, B.; Peroutka, R. J.; Landon, A.; Houng, S.; Muniandy, P. A.; Mazan-Mamczarz, K.; Steinhardt, J.; Livak, F.; Gartenhaus, R. B.] Univ Maryland, Marlene & Stewart Greenebaum Canc Ctr, Dept Med, Baltimore, MD 21201 USA.
[Chen, A. Y.; Corkum, C. P.; Michalak, T. I.] Mem Univ Newfoundland, Fac Med, Div Biomed Sci, Mol Virol & Hepatol Res Grp, St John, NF, Canada.
[Zhang, Y.; Lehrmann, E.; Becker, K. G.] NIA, Gene Express & Genom Unit, Genet Lab, NIH, Baltimore, MD 21224 USA.
[Shlyak, M.; Talwani, R.] Univ Maryland, Sch Med, Inst Human Virol, Dept Infect Dis, Baltimore, MD 21201 USA.
[Chen, Q. C.] Univ Maryland, Sch Med, Dept Pathol, Baltimore, MD 21201 USA.
[Gartenhaus, R. B.] Vet Adm Med Ctr, Baltimore, MD 21218 USA.
RP Gartenhaus, RB (reprint author), Univ Maryland, Med Ctr, Marlene & Stewart Greenebaum Canc Ctr, Dept Med, 655 West Baltimore St,BRB 9-011, Baltimore, MD 21201 USA.
EM rgartenhaus@som.umaryland.edu
FU Department of Veterans Affairs; National Institutes of Health
[R01AA017972, R01CA164311]; Canadian Institutes of Health Research
[MOP-126056]; Canada Research Chair Program in Viral
Hepatitis/Immunology; Intramural Research Program of the NIH, National
Institute on Aging
FX We are grateful to Dr El Mustapha Bahassi for the gift of CHK2 and its
truncated constructs. We thank Dr Michael MC Lai from the Institute of
Molecular Biology, Academia Sinica, Taiwan for generously sharing NS3/4A
constructs. We are thankful to Dr Michael Gale Jr (University of
Washington, WA, USA) for generously sharing a series of FLAG
epitope-tagged NS3/4A truncation and deletion mutant plasmids. We are
very grateful to Dr Eric Campeau for the use of pLenti-CMVTRE3G and
pLenti-CMV-rtTA3-Blast plasmids. We thank Dr Shyamasundaran Kottilil and
Dr Patricia M Mulrooney-Cousins for helpful discussions. Flow cytometry
analyses were performed at the University of Maryland Marlene and
Stewart Greenebaum Cancer Center Flow Cytometry Shared Service. This
work was supported in part by a Merit Review Award from the Department
of Veterans Affairs (RBG), R01AA017972 (RBG) and R01CA164311 (RBG) from
the National Institutes of Health, as well as MOP-126056 (TIM) from the
Canadian Institutes of Health Research and the Canada Research Chair
Program in Viral Hepatitis/Immunology (TIM). This research was also
supported in part by the Intramural Research Program of the NIH,
National Institute on Aging (YZ, EL and KGB).
NR 37
TC 2
Z9 3
U1 1
U2 1
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0950-9232
EI 1476-5594
J9 ONCOGENE
JI Oncogene
PD JUN 9
PY 2016
VL 35
IS 23
BP 2979
EP 2990
DI 10.1038/onc.2015.364
PG 12
WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
GA DO0NB
UT WOS:000377474500004
PM 26434584
ER
PT J
AU Hoang, DT
Venkatesh, BP
Han, S
Jo, J
Watanabe, G
Choi, MS
AF Danh-Tai Hoang
Venkatesh, B. Prasanna
Han, Seungju
Jo, Junghyo
Watanabe, Gentaro
Choi, Mahn-Soo
TI Scaling Law for Irreversible Entropy Production in Critical Systems
SO SCIENTIFIC REPORTS
LA English
DT Article
ID FREE-ENERGY DIFFERENCES; NONEQUILIBRIUM MEASUREMENTS;
EXPERIMENTAL-VERIFICATION; COSMOLOGICAL EXPERIMENTS;
STATISTICAL-MECHANICS; EQUALITY; THERMODYNAMICS; INFORMATION; PHYSICS
AB We examine the Jarzynski equality for a quenching process across the critical point of second-order phase transitions, where absolute irreversibility and the effect of finite-sampling of the initial equilibrium distribution arise in a single setup with equal significance. We consider the Ising model as a prototypical example for spontaneous symmetry breaking and take into account the finite sampling issue by introducing a tolerance parameter. The initially ordered spins become disordered by quenching the ferromagnetic coupling constant. For a sudden quench, the deviation from the Jarzynski equality evaluated from the ideal ensemble average could, in principle, depend on the reduced coupling constant epsilon(0) of the initial state and the system size L. We find that, instead of depending on epsilon(0) and L separately, this deviation exhibits a scaling behavior through a universal combination of epsilon(0) and L for a given tolerance parameter, inherited from the critical scaling laws of second-order phase transitions. A similar scaling law can be obtained for the finite-speed quench as well within the Kibble-Zurek mechanism.
C1 [Danh-Tai Hoang; Venkatesh, B. Prasanna; Jo, Junghyo; Watanabe, Gentaro] Asia Pacific Ctr Theoret Phys, Pohang 37673, Gyeongbuk, South Korea.
[Danh-Tai Hoang] NIDDK, NIH, Bethesda, MD 20892 USA.
[Danh-Tai Hoang] Quang Binh Univ, Dept Nat Sci, Dong Hoi 510000, Quang Binh, Vietnam.
[Venkatesh, B. Prasanna] Austrian Acad Sci, Inst Quantum Opt & Quantum Informat, Technikerstr 21a, A-6020 Innsbruck, Austria.
[Venkatesh, B. Prasanna] Univ Innsbruck, Inst Theoret Phys, A-6020 Innsbruck, Austria.
[Han, Seungju; Choi, Mahn-Soo] Korea Univ, Dept Phys, Seoul 02841, South Korea.
[Jo, Junghyo] Pohang Univ Sci & Technol POSTECH, Dept Phys, Pohang 37673, Gyeongbuk, South Korea.
[Watanabe, Gentaro] Inst for Basic Sci Korea, Ctr Theoret Phys Complex Syst, Daejeon 34051, South Korea.
[Watanabe, Gentaro] Univ Sci & Technol, 217 Gajeong Ro, Daejeon 34113, South Korea.
[Watanabe, Gentaro] Zhejiang Univ, Dept Phys, Hangzhou 310027, Zhejiang, Peoples R China.
RP Choi, MS (reprint author), Korea Univ, Dept Phys, Seoul 02841, South Korea.
EM choims@korea.ac.kr
RI Watanabe, Gentaro/N-9456-2014; Prasanna Venkatesh, B/D-8289-2017
FU National Research Foundation (NRF) [2015-003689]; Ministry of Education
of Korea through the BK21 Plus Initiative; Max Planck Society; MSIP of
Korea; Gyeongsangbuk-Do; Pohang City through the JRG at APCTP; NRF
[2012R1A1A2008028]; IBS [IBS-R024-D1]; Zhejiang University 100 Plan;
Junior 1000 Talents Plan of China
FX We thank Oscar Dahlsten and Carlo Danieli for helpful comments. S.H. and
M.-S.C. are supported by the National Research Foundation (NRF; Grant
No. 2015-003689) and by the Ministry of Education of Korea through the
BK21 Plus Initiative. D.-T.H., J.J., B.P.V. and G.W. are supported
jointly by the Max Planck Society, the MSIP of Korea, Gyeongsangbuk-Do
and Pohang City through the JRG at APCTP. BPV thanks Prof. Oriol
Romero-Isart for his support. GW also acknowledges support by the NRF
(Grant No. 2012R1A1A2008028), by the IBS (Grant No. IBS-R024-D1), by the
Zhejiang University 100 Plan, and by the Junior 1000 Talents Plan of
China.
NR 52
TC 0
Z9 0
U1 3
U2 7
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2045-2322
J9 SCI REP-UK
JI Sci Rep
PD JUN 9
PY 2016
VL 6
AR 27603
DI 10.1038/srep27603
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DN8RQ
UT WOS:000377347500001
PM 27277558
ER
PT J
AU Shinden, Y
Ueo, H
Tobo, T
Gamachi, A
Utou, M
Komatsu, H
Nambara, S
Saito, T
Ueda, M
Hirata, H
Sakimura, S
Takano, Y
Uchi, R
Kurashige, J
Akiyoshi, S
Iguchi, T
Eguchi, H
Sugimachi, K
Kubota, Y
Kai, Y
Shibuta, K
Kijima, Y
Yoshinaka, H
Natsugoe, S
Mori, M
Maehara, Y
Sakabe, M
Kamiya, M
Kakareka, JW
Pohida, TJ
Choyke, PL
Kobayashi, H
Ueo, H
Urano, Y
Mimori, K
AF Shinden, Yoshiaki
Ueo, Hiroki
Tobo, Taro
Gamachi, Ayako
Utou, Mitsuaki
Komatsu, Hisateru
Nambara, Sho
Saito, Tomoko
Ueda, Masami
Hirata, Hidenari
Sakimura, Shotaro
Takano, Yuki
Uchi, Ryutaro
Kurashige, Junji
Akiyoshi, Sayuri
Iguchi, Tomohiro
Eguchi, Hidetoshi
Sugimachi, Keishi
Kubota, Yoko
Kai, Yuichiro
Shibuta, Kenji
Kijima, Yuko
Yoshinaka, Heiji
Natsugoe, Shoji
Mori, Masaki
Maehara, Yoshihiko
Sakabe, Masayo
Kamiya, Mako
Kakareka, John W.
Pohida, Thomas J.
Choyke, Peter L.
Kobayashi, Hisataka
Ueo, Hiroaki
Urano, Yasuteru
Mimori, Koshi
TI Rapid diagnosis of lymph node metastasis in breast cancer using a new
fluorescent method with gamma-glutamyl hydroxymethyl rhodamine green
SO SCIENTIFIC REPORTS
LA English
DT Article
ID NUCLEIC-ACID AMPLIFICATION; RECOMMENDATIONS
AB Sentinel lymph node biopsy is performed as a standard procedure in breast cancer surgery, and the development of quick and simple methods to detect metastatic lesions is in high demand. Here, we validated a new fluorescent method using gamma-glutamyl hydroxymethyl rhodamine green to diagnose metastatic lymph nodes in breast cancer. One hundred and forty-nine lymph nodes from 38 breast cancer patients were evaluated in this study. Comparison of fluorescent and pathological images showed that this fluorescent method was successful for visualizing breast cancer cells in lymph nodes. This method had a sufficiently high sensitivity (97%), specificity (79%) and negative predictive value (99%) to render it useful for an intraoperative diagnosis of cancer. These preliminary findings suggest that this novel method is useful for distinguishing non-cancerous specimens from those in need of careful examination and could help save time and cost for surgeons and pathologists.
C1 [Shinden, Yoshiaki; Ueo, Hiroki; Komatsu, Hisateru; Nambara, Sho; Saito, Tomoko; Ueda, Masami; Hirata, Hidenari; Sakimura, Shotaro; Takano, Yuki; Uchi, Ryutaro; Kurashige, Junji; Akiyoshi, Sayuri; Iguchi, Tomohiro; Eguchi, Hidetoshi; Sugimachi, Keishi; Mimori, Koshi] Kagoshima Univ, Grad Sch Med & Dent Sci, Dept Surg Breast & Thyroid Surg, Kagoshima, Kagoshima 8908520, Japan.
[Shinden, Yoshiaki; Kijima, Yuko; Yoshinaka, Heiji; Natsugoe, Shoji] Kagoshima Univ, Grad Sch Med & Dent Sci, Dept Digest Surg Breast & Thyroid Surg, Kagoshima, Kagoshima 8908520, Japan.
[Ueo, Hiroki; Maehara, Yoshihiko] Kyushu Univ, Grad Sch Med Sci, Dept Surg & Sci, Fukuoka 8128582, Japan.
[Tobo, Taro; Utou, Mitsuaki] Kyushu Univ, Beppu Hosp, Dept Pathol, 4546 Tsurumihara, Beppu, Oita 8740838, Japan.
[Gamachi, Ayako] Oita Univ, Dept Pathol, Yufu 8795593, Japan.
[Kubota, Yoko; Kai, Yuichiro; Shibuta, Kenji; Ueo, Hiroaki] Ueo Breast Surg Hosp, Oita 8700854, Japan.
[Mori, Masaki] Osaka Univ, Dept Surg Gastroenterol, Grad Sch Med, 2-2 Yamadaoka, Suita, Osaka 5650871, Japan.
[Sakabe, Masayo; Kamiya, Mako; Urano, Yasuteru] Univ Tokyo, Grad Sch Med, Tokyo 1130033, Japan.
[Kakareka, John W.; Pohida, Thomas J.] NIH, Signal Proc & Instrumentat Sect, Div Computat Biosci, Ctr Informat Technol, Bldg 10, Bethesda, MD 20892 USA.
[Choyke, Peter L.; Kobayashi, Hisataka] NCI, Mol Imaging Program, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Urano, Yasuteru] CREST, AMED, Tokyo 1000004, Japan.
RP Mimori, K (reprint author), Kagoshima Univ, Grad Sch Med & Dent Sci, Dept Surg Breast & Thyroid Surg, Kagoshima, Kagoshima 8908520, Japan.; Urano, Y (reprint author), Univ Tokyo, Grad Sch Med, Tokyo 1130033, Japan.; Urano, Y (reprint author), CREST, AMED, Tokyo 1000004, Japan.
EM uranokun@m.u-tokyo.ac.jp; kmimori@beppu.kyushu-u.ac.jp
FU [25430111]; [25461953]; [25861199]; [25861200]; [24592005];
[21229015]
FX The following grants and foundations supported this work: Grants-in-Aid
for Scientific Research, grant numbers 25430111, 25461953, 25861199,
25861200, 24592005, and 21229015. We would like to thank Ms. M. Kasagi,
Ms. S. Kohno, Ms. K. Oda, Ms. M. Aoyagi, Ms. T. Kawano, Mr. Y. Komatsu
and Ms. Y. Abe for their assistance with the molecular biological and
pathological procedures.
NR 20
TC 1
Z9 1
U1 9
U2 15
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2045-2322
J9 SCI REP-UK
JI Sci Rep
PD JUN 9
PY 2016
VL 6
AR 27525
DI 10.1038/srep27525
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DN8PP
UT WOS:000377341800002
PM 27277343
ER
PT J
AU McFarland, JM
Cumming, BG
Butts, DA
AF McFarland, James M.
Cumming, Bruce G.
Butts, Daniel A.
TI Variability and Correlations in Primary Visual Cortical Neurons Driven
by Fixational Eye Movements
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
DE fixational eye movements; noise correlations; V1; variability
ID RESPONSE VARIABILITY; SPIKE TRAINS; CORTEX V1; RECEPTIVE-FIELDS; ONGOING
ACTIVITY; AUDITORY-CORTEX; MACAQUE V1; ATTENTION; MONKEYS; STATE
AB The ability to distinguish between elements of a sensory neuron's activity that are stimulus independent versus driven by the stimulus is critical for addressing many questions in systems neuroscience. This is typically accomplished by measuring neural responses to repeated presentations of identical stimuli and identifying the trial-variable components of the response as noise. In awake primates, however, small "fixational" eye movements (FEMs) introduce uncontrolled trial-to-trial differences in the visual stimulus itself, potentially confounding this distinction. Here, we describe novel analytical methods that directly quantify the stimulus-driven and stimulus-independent components of visual neuron responses in the presence of FEMs. We apply this approach, combined with precise model-based eye tracking, to recordings from primary visual cortex (V1), finding that standard approaches that ignore FEMs typically miss more than half of the stimulus-driven neural response variance, creating substantial biases in measures of response reliability. We show that these effects are likely not isolated to the particular experimental conditions used here, such as the choice of visual stimulus or spike measurement time window, and thus will be a more general problem for V1 recordings in awake primates. We also demonstrate that measurements of the stimulus-driven and stimulus-independent correlations among pairs of V1 neurons can be greatly biased by FEMs. These results thus illustrate the potentially dramatic impact of FEMs on measures of signal and noise in visual neuron activity and also demonstrate a novel approach for controlling for these eye-movement-induced effects.
C1 [McFarland, James M.; Butts, Daniel A.] Univ Maryland, Dept Biol, 1210 Biol Psychol Bldg 144, College Pk, MD 20815 USA.
[McFarland, James M.; Butts, Daniel A.] Univ Maryland, Program Neurosci & Cognit Sci, College Pk, MD 20815 USA.
[Cumming, Bruce G.] NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA.
RP Butts, DA (reprint author), Univ Maryland, Dept Biol, 1210 Biol Psychol Bldg 144, College Pk, MD 20815 USA.
EM dab@umd.edu
OI Butts, Daniel/0000-0002-0158-5317
FU National Science Foundation [IIS-1350990]; National Institutes of Health
[F32-EY-023921]; National Eye Institute Intramural Research Program
Grant
FX This work was supported by the National Science Foundation Grant
IIS-1350990 (D.A.B.) and the National Institutes of Health Grant
F32-EY-023921 (J.M.M) and National Eye Institute Intramural Research
Program Grant (B.G.C.). We thank D. Parker and I. Bunea for providing
excellent animal care and to M. Whiteway for helpful comments on the
manuscript.
NR 64
TC 0
Z9 0
U1 1
U2 2
PU SOC NEUROSCIENCE
PI WASHINGTON
PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA
SN 0270-6474
J9 J NEUROSCI
JI J. Neurosci.
PD JUN 8
PY 2016
VL 36
IS 23
BP 6225
EP 6241
DI 10.1523/JNEUROSCI.4660-15.2016
PG 17
WC Neurosciences
SC Neurosciences & Neurology
GA DQ2CE
UT WOS:000379007700011
PM 27277801
ER
PT J
AU Stalnaker, TA
Berg, B
Aujla, N
Schoenbaum, G
AF Stalnaker, Thomas A.
Berg, Ben
Aujla, Navkiran
Schoenbaum, Geoffrey
TI Cholinergic Interneurons Use Orbitofrontal Input to Track Beliefs about
Current State
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
DE cholinergic; orbitofrontal; rat; single unit; striatum
ID TONICALLY ACTIVE NEURONS; DORSOLATERAL STRIATUM; PREFRONTAL CORTEX;
DORSOMEDIAL STRIATUM; PRIMATE CAUDATE; INSULAR CORTEX; RAT STRIATUM;
IN-VIVO; MONKEY; ACETYLCHOLINE
AB When conditions change, organisms need to learn about the changed conditions without interfering with what they already know. To do so, they can assign the new learning to a new "state" and the old learning to a previous state. This state assignment is fundamental to behavioral flexibility. Cholinergic interneurons (CINs) in the dorsomedial striatum (DMS) are necessary for associative information to be compartmentalized in this way, but the mechanism by which they do so is unknown. Here we addressed this question by recording putative CINs from the DMS in rats performing a task consisting of a series of trial blocks, or states, that required the recall and application of contradictory associative information. We found that individual CINs in the DMS represented the current state throughout each trial. These state correlates were not observed in dorsolateral striatal CINs recorded in the same rats. Notably, DMS CIN ensembles tracked rats' beliefs about the current state such that, when states were miscoded, rats tended to make suboptimal choices reflecting the miscoding. State information held by the DMS CINs also depended completely on the orbitofrontal cortex, an area that has been proposed to signal environmental states. These results suggest that CINs set the stage for recalling associative information relevant to the current environment by maintaining a real-time representation of the current state. Such a role has novel implications for understanding the neural basis of a variety of psychiatric diseases, such as addiction or anxiety disorders, in which patients generalize inappropriately (or fail to generalize) between different environments.
C1 [Stalnaker, Thomas A.; Berg, Ben; Aujla, Navkiran; Schoenbaum, Geoffrey] NIDA, Intramural Res Program, Cellular Neurobiol Res Branch, Behav Neurophysiol Res Sect, 251 Bayview Blvd, Baltimore, MD 21224 USA.
[Schoenbaum, Geoffrey] Univ Maryland, Sch Med, Dept Anat & Neurobiol, Baltimore, MD 21201 USA.
[Schoenbaum, Geoffrey] Johns Hopkins Univ, Solomon H Snyder Dept Neurosci, Baltimore, MD 21218 USA.
RP Stalnaker, TA; Schoenbaum, G (reprint author), NIDA, Intramural Res Program, Cellular Neurobiol Res Branch, Behav Neurophysiol Res Sect, 251 Bayview Blvd, Baltimore, MD 21224 USA.
EM thomas.stalnaker@nih.gov; geoffrey.schoenbaum@nih.gov
FU Intramural Research Program at the National Institute on Drug Abuse
(NIDA-IRP)
FX This work was supported by the Intramural Research Program at the
National Institute on Drug Abuse (NIDA-IRP). We acknowledge the
assistance of Brandon Harvey, Director of the Optogenetics and
Transgenic Technology Core at the NIDA-IRP.
NR 59
TC 4
Z9 4
U1 2
U2 3
PU SOC NEUROSCIENCE
PI WASHINGTON
PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA
SN 0270-6474
J9 J NEUROSCI
JI J. Neurosci.
PD JUN 8
PY 2016
VL 36
IS 23
BP 6242
EP 6257
DI 10.1523/JNEUROSCI.0157-16.2016
PG 16
WC Neurosciences
SC Neurosciences & Neurology
GA DQ2CE
UT WOS:000379007700012
PM 27277802
ER
PT J
AU Knoll, AT
Halladay, LR
Holmes, AJ
Levitt, P
AF Knoll, Allison T.
Halladay, Lindsay R.
Holmes, Andrew J.
Levitt, Pat
TI Quantitative Trait Loci and a Novel Genetic Candidate for Fear Learning
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
DE anxiety; associative learning; HCN1; individual differences;
quantitative trait gene; threat detection
ID POSTTRAUMATIC-STRESS-DISORDER; ACTIVATED CATION CHANNELS;
NUCLEOTIDE-GATED CHANNELS; AUXILIARY SUBUNIT TRIP8B; CA1 PYRAMIDAL
NEURONS; HCN CHANNELS; BASOLATERAL AMYGDALA; ANXIETY DISORDERS; I-H;
CONDITIONED FEAR
AB Trauma- and stress-related disorders are clinically heterogeneous and associated with substantial genetic risk. Understanding the biological origins of heterogeneity of key intermediate phenotypes such as cognition and emotion can provide novel mechanistic insights into disorder pathogenesis. Performing quantitative genetics in animal models is a tractable strategy for examining both the genetic basis of intermediate phenotypes and functional testing of candidate quantitative traits genes (QTGs). Here, existing and newly collected data were used for collaborative genome-wide mapping of cued fear acquisition and expression in 65 mouse strains from the BXD genetic reference panel. For fear acquisition, we identified a significant locus on chromosome (Chr) 10 and eight suggestive loci on Chr 2, 4, 5, 11, 13, and 15. For fear expression, we identified one significant and another highly suggestive locus on Chr 13, as well as four suggestive loci on Chr 10, 11, and X. Across these loci, 60 putative QTGs were identified. The quantitative trait locus on distal Chr 13 contained a single, highly promising gene at the location of the peak likelihood ratio statistic score. The gene, hyperpolarization-activated cyclic nucleotide-gated channel 1 (Hcn1), regulates neuronal excitability. Validation experiments using behavioral pharmacology revealed that functional Hcn channels in the basolateral amygdala are necessary for conditioned fear acquisition and expression. Hcn1, together with the other candidate QTGs, thus provide new targets for neurobiological and treatment studies of fear learning and trauma-and stress-related disorders.
C1 [Knoll, Allison T.; Levitt, Pat] Childrens Hosp Los Angeles, Program Dev Neurogenet, Inst Developing Mind, Saban Res Inst, Los Angeles, CA 90027 USA.
[Levitt, Pat] Univ So Calif, Keck Sch Med, Dept Pediat, Los Angeles, CA 90089 USA.
[Halladay, Lindsay R.; Holmes, Andrew J.] NIAAA, NIH, Lab Behav & Genom Neurosci, Bethesda, MD 20814 USA.
RP Levitt, P (reprint author), Childrens Hosp Los Angeles, Mail Stop 135,4650 Sunset Blvd, Los Angeles, CA 90027 USA.
EM plevitt@med.usc.edu
FU Simms/Mann Chair in Developmental Neurogenetics and National Institute
of Mental Health, National Institutes of Health [R01 MH080759]; National
Institute on Alcohol Abuse and Alcoholism Intramural Program; Autism
Speaks (Translational Postdoctoral Fellowship) [7595]
FX This work was supported by the Simms/Mann Chair in Developmental
Neurogenetics and National Institute of Mental Health, National
Institutes of Health (Grant R01 MH080759 to P.L.), the National
Institute on Alcohol Abuse and Alcoholism Intramural Program (A.J.H.),
and Autism Speaks (Translational Postdoctoral Fellowship 7595 to
A.T.K.). We thank Dr. Megan Mulligan and Dr. Robert Williams for helpful
comments on this manuscript.
NR 77
TC 1
Z9 1
U1 2
U2 2
PU SOC NEUROSCIENCE
PI WASHINGTON
PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA
SN 0270-6474
J9 J NEUROSCI
JI J. Neurosci.
PD JUN 8
PY 2016
VL 36
IS 23
BP 6258
EP 6268
DI 10.1523/JNEUROSCI.0177-16.2016
PG 11
WC Neurosciences
SC Neurosciences & Neurology
GA DQ2CE
UT WOS:000379007700013
PM 27277803
ER
PT J
AU Carstens, KE
Phillips, ML
Pozzo-Miller, L
Weinberg, RJ
Dudek, SM
AF Carstens, Kelly E.
Phillips, Mary L.
Pozzo-Miller, Lucas
Weinberg, Richard J.
Dudek, Serena M.
TI Perineuronal Nets Suppress Plasticity of Excitatory Synapses on CA2
Pyramidal Neurons
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
DE critical period; extracellular matrix; hippocampus; long-term
potentiation
ID LATERAL GENICULATE-NUCLEUS; CHONDROITIN SULFATE PROTEOGLYCANS;
HIPPOCAMPAL AREA CA2; SYNAPTIC PLASTICITY; EXTRACELLULAR-MATRIX;
VISUAL-CORTEX; ENVIRONMENTAL ENRICHMENT; TYROSINE-PHOSPHATASE; OXIDATIVE
STRESS; HYALURONIC-ACID
AB Long-term potentiation of excitatory synapses on pyramidal neurons in the stratum radiatum rarely occurs in hippocampal area CA2. Here, we present evidence that perineuronal nets (PNNs), a specialized extracellular matrix typically localized around inhibitory neurons, also surround mouse CA2 pyramidal neurons and envelop their excitatory synapses. CA2 pyramidal neurons express mRNA transcripts for the major PNN component aggrecan, identifying these neurons as a novel source for PNNs in the hippocampus. We also found that disruption of PNNs allows synaptic potentiation of normally plasticity-resistant excitatory CA2 synapses; thus, PNNs play a role in restricting synaptic plasticity in area CA2. Finally, we found that postnatal development of PNNs on CA2 pyramidal neurons is modified by early-life enrichment, suggesting that the development of circuits containing CA2 excitatory synapses are sensitive to manipulations of the rearing environment.
C1 [Carstens, Kelly E.; Dudek, Serena M.] NIEHS, Neurobiol Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.
[Carstens, Kelly E.; Weinberg, Richard J.] Univ N Carolina, Dept Cell Biol & Physiol, Chapel Hill, NC 27599 USA.
[Phillips, Mary L.; Pozzo-Miller, Lucas] Univ Alabama Birmingham, Civitan Int Res Ctr, Dept Neurobiol, Birmingham, AL 35294 USA.
RP Dudek, SM (reprint author), NIEHS, Neurobiol Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.
EM dudek@niehs.nih.gov
OI Weinberg, Richard/0000-0001-9689-7278
FU Intramural Research Program of the National Institute of Environmental
Health Sciences, National Institutes of Health [Z01 ES100221]; National
Institute of Neurological Disorders and Stroke [R01 NS039444]; National
Institutes of Health Grant [NS-065027]
FX This work was supported by the Intramural Research Program of the
National Institute of Environmental Health Sciences, National Institutes
of Health (Z01 ES100221); by National Institute of Neurological
Disorders and Stroke Award R01 NS039444 (to R.J.W.); and by National
Institutes of Health Grant NS-065027 (to L.P.-M.). We thank Susan
Burette for technical assistance with electron microscopy, the National
Institute of Environmental Health Sciences Fluorescence Microscopy and
Imaging Center and the animal care staff for support, and David
Armstrong and Georgia Alexander for input on this manuscript.
NR 52
TC 5
Z9 5
U1 2
U2 6
PU SOC NEUROSCIENCE
PI WASHINGTON
PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA
SN 0270-6474
J9 J NEUROSCI
JI J. Neurosci.
PD JUN 8
PY 2016
VL 36
IS 23
BP 6312
EP 6320
DI 10.1523/JNEUROSCI.0245-16.2016
PG 9
WC Neurosciences
SC Neurosciences & Neurology
GA DQ2CE
UT WOS:000379007700017
PM 27277807
ER
PT J
AU Fan, J
He, QJ
Liu, Y
Zhang, FW
Yang, XY
Wang, Z
Lu, N
Fan, WP
Lin, LS
Niu, G
He, NY
Song, JB
Chen, XY
AF Fan, Jing
He, Qianjun
Liu, Yi
Zhang, Fuwu
Yang, Xiangyu
Wang, Zhe
Lu, Nan
Fan, Wenpei
Lin, Lisen
Niu, Gang
He, Nongyue
Song, Jibin
Chen, Xiaoyuan
TI Light-Responsive Biodegradable Nanomedicine Overcomes Multidrug
Resistance via NO-Enhanced Chemosensitization
SO ACS APPLIED MATERIALS & INTERFACES
LA English
DT Article
DE nitric oxide (NO); light-responsive; mPEG-PLGA; chemotherapy; multidrug
resistance (MDR)
ID NITRIC-OXIDE; TUMOR HYPOXIA; CANCER-CELLS; GENE-EXPRESSION; MDR1 GENE;
PROTEIN; DOXORUBICIN; CARCINOMA; ANGIOGENESIS; CISPLATIN
AB Multidrug resistance (MDR) is responsible for the relatively low effectiveness of chemotherapeutics. Herein, a nitric oxide (NO) gas-enhanced chemosensitization strategy is proposed to overcome MDR by construction of a biodegradable nanomedicine formula based on BNN6/DOX coloaded monomethoxy(polyethylene glycol)-poly(lactic-co-glycolic acid) (mPEG-PLGA). On one hand, the nanomedicine features high biocompatibility due to the high density of PEG and biodegradable PLGA. On the other hand, the nanoformula exhibits excellent stability under physiological conditions but exhibits stimuli-responsive decomposition of BNN6 for NO gas release upon ultraviolet-visible irradiation. More importantly, after NO release is triggered, gas molecules are generated that break the nanoparticle shell and lead to the release of doxorubicin. Furthermore, NO was demonstrated to reverse the MDR of tumor cells and enhance the chemosensitization for doxorubicin therapy.
C1 [Fan, Jing; Yang, Xiangyu; He, Nongyue] Southeast Univ, State Key Lab Bioelect, Nanjing 210096, Jiangsu, Peoples R China.
[Fan, Jing; Liu, Yi; Zhang, Fuwu; Yang, Xiangyu; Wang, Zhe; Lu, Nan; Fan, Wenpei; Lin, Lisen; Niu, Gang; Song, Jibin; Chen, Xiaoyuan] NIBIB, Lab Mol Imaging & Nanomed LOMIN, NIH, Bethesda, MD 20892 USA.
[He, Qianjun; Fan, Wenpei] Shenzhen Univ, Sch Med, Dept Biomed Engn, Guangdong Key Lab Biomed Measurements & Ultrasoun, Shenzhen 518060, Guangdong, Peoples R China.
[Fan, Jing] Guangxi Med Univ, Biol Target Diag & Treatment Ctr, Nanning 530021, Guangxi, Peoples R China.
RP He, NY (reprint author), Southeast Univ, State Key Lab Bioelect, Nanjing 210096, Jiangsu, Peoples R China.; Song, JB; Chen, XY (reprint author), NIBIB, Lab Mol Imaging & Nanomed LOMIN, NIH, Bethesda, MD 20892 USA.
EM nyhe1958@163.com; jibin.song@nih.gov; shawn.chen@nih.gov
RI HE, QIANJUN/M-2642-2013
OI HE, QIANJUN/0000-0003-0689-8838
FU National Institute of Biomedical Imaging and Bioengineering, National
Institutes of Health; National Key Program for Developing Basic Research
of China [2014CB744501]; NSFC [61271056, 61471168, 61527806]; Shenzhen
Basic Research Program [JCYJ20160226110137243]; China Scholarship
Council
FX We thank the financial support from the Intramural Research Program,
National Institute of Biomedical Imaging and Bioengineering, National
Institutes of Health, the National Key Program for Developing Basic
Research of China (Grant 2014CB744501), the NSFC (Grants 61271056,
61471168, and 61527806), the Shenzhen Basic Research Program (Grant
JCYJ20160226110137243), and the State Scholarship Fund from the China
Scholarship Council.
NR 32
TC 13
Z9 13
U1 33
U2 57
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1944-8244
J9 ACS APPL MATER INTER
JI ACS Appl. Mater. Interfaces
PD JUN 8
PY 2016
VL 8
IS 22
BP 13804
EP 13811
DI 10.1021/acsami.6b03737
PG 8
WC Nanoscience & Nanotechnology; Materials Science, Multidisciplinary
SC Science & Technology - Other Topics; Materials Science
GA DO2WQ
UT WOS:000377642100017
PM 27213922
ER
PT J
AU Zholdybayeva, EV
Talzhanov, YA
Aitkulova, AM
Tarlykov, PV
Kulmambetova, GN
Iskakova, AN
Dzholdasbekova, AU
Visternichan, OA
Taizhanova, DZ
Ramanculov, YM
AF Zholdybayeva, Elena V.
Talzhanov, Yerkebulan A.
Aitkulova, Akbota M.
Tarlykov, Pavel V.
Kulmambetova, Gulmira N.
Iskakova, Aisha N.
Dzholdasbekova, Aliya U.
Visternichan, Olga A.
Taizhanova, Dana Zh
Ramanculov, Yerlan M.
TI Genetic risk factors for restenosis after percutaneous coronary
intervention in Kazakh population
SO HUMAN GENOMICS
LA English
DT Article
DE Coronary heart disease; Restenosis; SNP; Genotyping
ID NITRIC-OXIDE SYNTHASE; IN-STENT RESTENOSIS; ARTERY-DISEASE;
MYOCARDIAL-INFARCTION; G894T POLYMORPHISM; HEART-DISEASE; ASSOCIATION;
ANGIOPLASTY; PLACEMENT; RECEPTOR
AB Background: After coronary stenting, the risk of developing restenosis is from 20 to 35 %. The aim of the present study is to investigate the association of genetic variation in candidate genes in patients diagnosed with restenosis in the Kazakh population.
Methods: Four hundred fifty-nine patients were recruited to the study; 91 patients were also diagnosed with diabetes and were excluded from the sampling. DNA was extracted with the salting-out method. The patients were genotyped for 53 single-nucleotide polymorphisms. Genotyping was performed on the QuantStudio 12K Flex (Life Technologies). Differences in distribution of BMI score among different genotype groups were compared by analysis of variance (ANOVA). Also, statistical analysis was performed using R and PLINK v.1.07. Haplotype frequencies and LD measures were estimated by using the software Haploview 4.2.
Results: A logistic regression analysis found a significant difference in restenosis rates for different genotypes. FGB (rs1800790) is significantly associated with restenosis after stenting (OR = 2.924, P = 2.3E-06, additive model) in the Kazakh population. CD14 (rs2569190) showed a significant association in the additive (OR = 0.08033, P = 2.11E-09) and dominant models (OR = 0.05359, P = 4.15E-11). NOS3 (rs1799983) was also highly associated with development of restenosis after stenting in additive (OR = 20.05, P = 2.74 E-12) and recessive models (OR = 22.24, P = 6.811E-10).
Conclusions: Our results indicate that FGB (rs1800790), CD14 (rs2569190), and NOS3 (rs1799983) SNPs could be genetic markers for development of restenosis in Kazakh population. Adjustment for potential confounder factor BMI gave almost the same results.
C1 [Zholdybayeva, Elena V.; Talzhanov, Yerkebulan A.; Aitkulova, Akbota M.; Tarlykov, Pavel V.; Kulmambetova, Gulmira N.; Iskakova, Aisha N.; Ramanculov, Yerlan M.] Natl Biotechnol Ctr, 13-5 KorgalzhinskoeHighway, Astana, Kazakhstan.
[Dzholdasbekova, Aliya U.] Natl Sci Med Res Ctr, 42 Abylai Khan Ave, Astana, Kazakhstan.
[Visternichan, Olga A.; Taizhanova, Dana Zh] Karaganda State Med Univ, 40 Gogol St, Karaganda, Kazakhstan.
[Ramanculov, Yerlan M.] Nazarbayev Univ, Sch Sci & Technol, 53 Kabanbay Batyr Ave, Astana, Kazakhstan.
[Iskakova, Aisha N.] Al Farabi Kazakh Natl Univ, Alma Ata, Kazakhstan.
RP Zholdybayeva, EV (reprint author), Natl Biotechnol Ctr, 13-5 KorgalzhinskoeHighway, Astana, Kazakhstan.
EM lenazhol@gmail.com
RI Akhmadyarova, Bota/R-4730-2016; Tarlykov, Pavel/C-2587-2012;
OI Tarlykov, Pavel/0000-0003-2075-307X; Iskakova, Aisha/0000-0002-0631-062X
FU Ministry of Education and Science of the Republic of Kazakhstan
[0112PK00361]
FX This work was supported by a grant #0112PK00361 from the Ministry of
Education and Science of the Republic of Kazakhstan.
NR 46
TC 0
Z9 0
U1 5
U2 6
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1473-9542
EI 1479-7364
J9 HUM GENOMICS
JI Hum. Genomics
PD JUN 8
PY 2016
VL 10
AR 15
DI 10.1186/s40246-016-0077-z
PG 8
WC Genetics & Heredity
SC Genetics & Heredity
GA DO4XP
UT WOS:000377788500001
PM 27277665
ER
PT J
AU Song, JB
Wang, F
Yang, XY
Ning, B
Harp, MG
Culp, SH
Hu, S
Huang, P
Nie, LM
Chen, JY
Chen, XY
AF Song, Jibin
Wang, Feng
Yang, Xiangyu
Ning, Bo
Harp, Mary G.
Culp, Stephen H.
Hu, Song
Huang, Peng
Nie, Liming
Chen, Jingyi
Chen, Xiaoyuan
TI Gold Nanoparticle Coated Carbon Nanotube Ring with Enhanced Raman
Scattering and Photothermal Conversion Property for Theranostic
Applications
SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Article
ID IN-VIVO; PLASMONIC VESICLES; GRAPHENE OXIDE; CANCER-THERAPY;
DRUG-DELIVERY; SERS; NANOSTRUCTURES; MOLECULES; SURFACE; PHOTODETECTION
AB We report a new type of carbon nanotube ring (CNTR) coated with gold nanoparticles (CNTR@AuNPs) using CNTR as a template and surface attached redox-active polymer as a reducing agent. This nanostructure of CNTR bundle embedded in the gap of closely attached AuNPs can play multiple roles as a Raman probe to detect cancer cells and a photoacoustic (PA) contrast agent for imaging-guided cancer therapy. The CNTR@AuNP exhibits substantially higher Raman and optical signals than CNTR coated with a complete Au shell (CNTR@AuNS) and straight CNT@AuNP. The extinction intensity of CNTR@AuNP is about 120-fold higher than that of CNTR at 808 rim, and the surface enhanced Raman scattering (SERS) signal of CNTR@AuNP is about 110 times stronger than that of CNTR, presumably due to the combined effects of enhanced coupling between the embedded CNTR and the plasmon mode of the closely attached AuNPs, and the strong electromagnetic field in the cavity of the AuNP shell originated from the intercoupling of AuNPs. The greatly enhanced PA signal and photothermal conversion property of CNTR@AuNP were successfully employed for imaging and imaging-guided cancer therapy in two tumor xenograft models. Experimental observations were further supported by numerical simulations and perturbation theory analysis.
C1 [Song, Jibin; Yang, Xiangyu; Huang, Peng; Nie, Liming; Chen, Xiaoyuan] Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed LOMIN, NIH, Bethesda, MD 20892 USA.
[Wang, Feng; Chen, Jingyi] Univ Arkansas, Dept Chem & Biochem, Fayetteville, AR 72701 USA.
[Ning, Bo; Hu, Song] Univ Virginia, Dept Biomed Engn, Charlottesville, VA 22903 USA.
[Harp, Mary G.; Culp, Stephen H.] Univ Virginia, Dept Urol, Charlottesville, VA 22903 USA.
RP Chen, XY (reprint author), Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed LOMIN, NIH, Bethesda, MD 20892 USA.
EM shawn.chen@nih.gov
RI Huang, Peng/R-2480-2016; Chen, Jingyi/E-7168-2010;
OI Huang, Peng/0000-0003-3651-7813; Chen, Jingyi/0000-0003-0012-9640; Ning,
Bo/0000-0002-6006-5696
FU Intramural Research Program of the National Institute of Biomedical
Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH);
Arkansas Breast Cancer Research Program; Arkansas Bioscience Institute
FX This work was supported by the Intramural Research Program of the
National Institute of Biomedical Imaging and Bioengineering (NIBIB),
National Institutes of Health (NIH), and the Arkansas Breast Cancer
Research Program and the Arkansas Bioscience Institute.
NR 47
TC 9
Z9 9
U1 119
U2 246
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0002-7863
J9 J AM CHEM SOC
JI J. Am. Chem. Soc.
PD JUN 8
PY 2016
VL 138
IS 22
BP 7005
EP 7015
DI 10.1021/jacs.5b13475
PG 11
WC Chemistry, Multidisciplinary
SC Chemistry
GA DO2XC
UT WOS:000377643300021
PM 27193381
ER
PT J
AU Thanos, PK
Kim, R
Delis, F
Ananth, M
Chachati, G
Rocco, MJ
Masad, I
Muniz, JA
Grant, SC
Gold, MS
Cadet, JL
Volkow, ND
AF Thanos, Panayotis K.
Kim, Ronald
Delis, Foteini
Ananth, Mala
Chachati, George
Rocco, Mark J.
Masad, Ihssan
Muniz, Jose A.
Grant, Samuel C.
Gold, Mark S.
Cadet, Jean Lud
Volkow, Nora D.
TI Chronic Methamphetamine Effects on Brain Structure and Function in Rats
SO PLOS ONE
LA English
DT Article
ID PONTINE RETICULAR-FORMATION; HIGH-DOSE METHAMPHETAMINE; DEFAULT MODE
NETWORK; CEREBRAL-BLOOD-FLOW; MICROGLIAL ACTIVATION; DOPAMINE
TRANSPORTERS; PROTRACTED ABSTINENCE; INDUCED NEUROTOXICITY; NEUROTROPHIC
FACTOR; IN-VITRO
AB Methamphetamine (MA) addiction is a growing epidemic worldwide. Chronic MA use has been shown to lead to neurotoxicity in rodents and humans. Magnetic resonance imaging (MRI) studies in MA users have shown enlarged striatal volumes and positron emission tomography (PET) studies have shown decreased brain glucose metabolism (BGluM) in the striatum of detoxified MA users. The present study examines structural changes of the brain, observes microglial activation, and assesses changes in brain function, in response to chronic MA treatment. Rats were randomly split into three distinct treatment groups and treated daily for four months, via i.p. injection, with saline (controls), or low dose (LD) MA (4 mg/kg), or high dose (HD) MA (8 mg/kg). Sixteen weeks into the treatment period, rats were injected with a glucose analog, [F-18] fluorodeoxyglucose (FDG), and their brains were scanned with micro-PET to assess regional BGluM. At the end of MA treatment, magnetic resonance imaging at 21T was performed on perfused rats to determine regional brain volume and in vitro [H-3]PK 11195 autoradiography was performed on fresh-frozen brain tissue to measure microglia activation. When compared with controls, chronic HD MA-treated rats had enlarged striatal volumes and increases in [H-3]PK 11195 binding in striatum, the nucleus accumbens, frontal cortical areas, the rhinal cortices, and the cerebellar nuclei. FDG microPET imaging showed that LD MA-treated rats had higher BGluM in insular and somatosensory cortices, face sensory nucleus of the thalamus, and brainstem reticular formation, while HD MA-treated rats had higher BGluM in primary and higher order somatosensory and the retrosplenial cortices, compared with controls. HD and LD MA-treated rats had lower BGluM in the tail of the striatum, rhinal cortex, and subiculum and HD MA also had lower BGluM in hippocampus than controls. These results corroborate clinical findings and help further examine the mechanisms behind MA-induced neurotoxicity.
C1 [Thanos, Panayotis K.; Chachati, George; Rocco, Mark J.] Univ Buffalo, Behav Neuropharmacol & Neuroimaging Lab Addict, Res Inst Addict, Buffalo, NY USA.
[Kim, Ronald] Univ N Carolina, Dept Psychol, Chapel Hill, NC USA.
[Delis, Foteini] Univ Ioannina, Sch Med, Dept Pharmacol, GR-45110 Ioannina, Greece.
[Ananth, Mala] SUNY Stony Brook, Dept Neurosci, Stony Brook, NY 11794 USA.
[Masad, Ihssan; Muniz, Jose A.; Grant, Samuel C.] Natl High Magnet Field Lab, Tallahassee, FL USA.
[Gold, Mark S.] Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA.
[Cadet, Jean Lud] NIDA, Mol Neuropsychiat Res Branch, NIH, Dept Hlth & Human Serv, Baltimore, MD USA.
[Volkow, Nora D.] NIAAA, Lab Neuroimaging, NIH, Dept Hlth & Human Serv, Bethesda, MD USA.
RP Thanos, PK (reprint author), Univ Buffalo, Behav Neuropharmacol & Neuroimaging Lab Addict, Res Inst Addict, Buffalo, NY USA.
EM pthanos@ria.buffalo.edu
OI Grant, Samuel/0000-0001-7738-168X
FU National Institutes of Health; National Institute on Alcohol and
Alcoholism [AA11034]; Research Foundation of New York [RIAQ094]
FX Funding was provided by National Institutes of Health; National
Institute on Alcohol and Alcoholism, AA11034; and Research Foundation of
New York, RIAQ094.
NR 75
TC 5
Z9 5
U1 8
U2 11
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUN 8
PY 2016
VL 11
IS 6
AR e0155457
DI 10.1371/journal.pone.0155457
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DO1TJ
UT WOS:000377561700005
PM 27275601
ER
PT J
AU Wooddell, LJ
Kaburu, SSK
Rosenberg, KL
Meyer, JS
Suomi, SJ
Dettmer, AM
AF Wooddell, Lauren J.
Kaburu, Stefano S. K.
Rosenberg, Kendra L.
Meyer, Jerrold S.
Suomi, Stephen J.
Dettmer, Amanda M.
TI Matrilineal Behavioral and Physiological Changes following the Death of
a Non-Alpha Matriarch in Rhesus Macaques (Macaca mulatta)
SO PLOS ONE
LA English
DT Article
ID PITUITARY-ADRENOCORTICAL ACTIVITY; PAPIO-HAMADRYAS-URSINUS; CORTISOL
CONCENTRATIONS; CHACMA BABOONS; HAIR CORTISOL; KILLER WHALES; WILD
BABOONS; SOCIAL RANK; MONKEYS; DOMINANCE
AB In many species, the loss of alpha matriarchs is associated with a number of negative outcomes such as troop fission, eviction, wounding, and reduced vitality. However, whether the dramatic consequences of their loss are due to their role as an old experienced figure or to their alpha status remains unclear. We tested the hypothesis that in a semi-free ranging colony of rhesus macaques (Macaca mulatta), the death of a non-alpha matriarch, who had a large set of kin, would lead to changes in behavior and physiological stress within her matriline. Following her death, her matriline increased in aggression, vigilance, and social grooming. Additionally, hierarchical stability, measured by levels of rank changes, decreased within her matriline, and levels of intense aggression by high-ranking animals were more frequent, as well as matrilineal wounding. Although ordinal rank was positively associated with higher chronic hair cortisol concentrations (HCCs) in the months before the matriarch's death, following her death, only those who experienced large increases in rank within her matriline displayed higher HCCs. Changes in matrilineal stability, aggression, behavior, and HCCs within the other two matrilines in the troop were not evident, although caution is needed due to the small sample sizes. We conclude that the death of the non-alpha matriarch led to matrilineal instability, characterized by higher levels of aggression and subsequent vigilance, rank changes, physiological stress, and grooming. We suggest that non-alpha matriarchs with a large number of kin and social support can be integral to the stability of matrilines.
C1 [Wooddell, Lauren J.; Suomi, Stephen J.; Dettmer, Amanda M.] NIH, Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Poolesville, MD USA.
[Kaburu, Stefano S. K.] Univ Calif Davis, Sch Vet Med, Dept Populat Hlth & Reprod, Davis, CA 95616 USA.
[Rosenberg, Kendra L.; Meyer, Jerrold S.] Univ Massachusetts, Dept Psychol & Brain Sci, Amherst, MA 01003 USA.
RP Wooddell, LJ (reprint author), NIH, Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Poolesville, MD USA.
EM lauren.wooddell@nih.gov
FU Division of Intramural Research, National Institute of Child Health and
Human Development [1ZIAHD001107-32]
FX This work was supported by the Division of Intramural Research, National
Institute of Child Health and Human Development, 1ZIAHD001107-32,
awarded to SJS,
https://www.nichd.nih.gov/about/org/dir/Pages/index.aspx. The funders
had no role in study design, data collection and analysis, decision to
publish, or preparation of the manuscript.
NR 72
TC 1
Z9 1
U1 7
U2 9
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUN 8
PY 2016
VL 11
IS 6
AR e0157108
DI 10.1371/journal.pone.0157108
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DO1TJ
UT WOS:000377561700069
PM 27275743
ER
PT J
AU Schoch, CL
Karsch-Mizrachi, I
Ostell, JM
AF Schoch, Conrad L.
Karsch-Mizrachi, Ilene
Ostell, James M.
TI In memoriam -Scott Federhen (October 21, 1952-May 5, 2016)
SO STANDARDS IN GENOMIC SCIENCES
LA English
DT Biographical-Item
C1 [Schoch, Conrad L.; Karsch-Mizrachi, Ilene; Ostell, James M.] Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bldg 45,8600 Rockville Pike, Bethesda, MD 20894 USA.
RP Schoch, CL (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bldg 45,8600 Rockville Pike, Bethesda, MD 20894 USA.
EM schoch2@ncbi.nlm.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1944-3277
J9 STAND GENOMIC SCI
JI Stand. Genomic Sci.
PD JUN 8
PY 2016
VL 11
AR 41
DI 10.1186/s40793-016-0160-z
PG 2
WC Genetics & Heredity; Microbiology
SC Genetics & Heredity; Microbiology
GA DO7HL
UT WOS:000377953100001
ER
PT J
AU Nussinov, R
AF Nussinov, Ruth
TI Introduction to Protein Ensembles and Allostery
SO CHEMICAL REVIEWS
LA English
DT Editorial Material
ID HEMOGLOBIN; MODEL
C1 [Nussinov, Ruth] NCI, Computat Struct Biol Sect, Bethesda, MD 20892 USA.
[Nussinov, Ruth] Tel Aviv Univ, Sch Med, Dept Human Genet, IL-69978 Tel Aviv, Israel.
RP Nussinov, R (reprint author), NCI, Computat Struct Biol Sect, Bethesda, MD 20892 USA.; Nussinov, R (reprint author), Tel Aviv Univ, Sch Med, Dept Human Genet, IL-69978 Tel Aviv, Israel.
EM NussinoR@helix.nih.gov
NR 8
TC 1
Z9 1
U1 4
U2 16
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0009-2665
EI 1520-6890
J9 CHEM REV
JI Chem. Rev.
PD JUN 8
PY 2016
VL 116
IS 11
SI SI
BP 6263
EP 6266
DI 10.1021/acs.chemrev.6b00283
PG 4
WC Chemistry, Multidisciplinary
SC Chemistry
GA DO2WK
UT WOS:000377641500001
PM 27268255
ER
PT J
AU Venditti, V
Egner, TK
Clore, GM
AF Venditti, Vincenzo
Egner, Timothy K.
Clore, G. Marius
TI Hybrid Approaches to Structural Characterization of Conformational
Ensembles of Complex Macromolecular Systems Combining NMR Residual
Dipolar Couplings and Solution X-ray Scattering
SO CHEMICAL REVIEWS
LA English
DT Review
ID PARAMAGNETIC RELAXATION ENHANCEMENT; SUGAR PHOSPHOTRANSFERASE SYSTEM;
SMALL-ANGLE SCATTERING; PROTEIN-PROTEIN COMPLEXES; MOLECULAR-WEIGHT
PROTEINS; LIQUID-CRYSTALLINE MEDIUM; RIGID-BODY MINIMIZATION; BACTERIAL
ENZYME I; TENSOR-FREE METHOD; N-TERMINAL DOMAIN
AB Solving structures or structural ensembles of large macromolecular systems in solution poses a challenging problem. While NMR provides structural information at atomic resolution, increased spectral complexity, chemical shift overlap, and short transverse relaxation times (associated with slow tumbling) render application of the usual techniques that have been so successful for medium sized systems (<50 kDa) difficult. Solution X-ray scattering, on the other hand, is not limited by molecular weight but only provides low resolution structural information related to the overall shape and size of the system under investigation. Here we review how combining atomic resolution structures of smaller domains with sparse experimental data afforded by NMR residual dipolar couplings (which yield both orientational and shape information) and solution X-ray scattering data in rigid-body simulated annealing calculations provides a powerful approach for investigating the structural aspects of conformational dynamics in large multidomain proteins. The application of this hybrid methodology is illustrated for the 128 kDa diner of bacterial Enzyme I which exists in a variety of open and closed states that are sampled at various points in the catalytic cycles, and for the capsid protein of the human immunodeficiency virus.
C1 [Venditti, Vincenzo; Egner, Timothy K.] Iowa State Univ, Dept Chem, Ames, IA 50011 USA.
[Venditti, Vincenzo] Iowa State Univ, Roy J Carver Dept Biochem Biophys & Mol Biol, Ames, IA 50011 USA.
[Clore, G. Marius] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
RP Venditti, V (reprint author), Iowa State Univ, Dept Chem, Ames, IA 50011 USA.; Venditti, V (reprint author), Iowa State Univ, Roy J Carver Dept Biochem Biophys & Mol Biol, Ames, IA 50011 USA.; Clore, GM (reprint author), NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
EM venditti@iastate.edu; mariusc@mail.nih.gov
FU Intramural Program of the National Institute of Diabetes and Digestive
and Kidney Diseases, NIH; Iowa State University
FX We thank Charles Schwieters for helpful discussions. This work was
supported by the Intramural Program of the National Institute of
Diabetes and Digestive and Kidney Diseases, NIH (G.M.C.) and by startup
funding from Iowa State University (v.v.).
NR 176
TC 3
Z9 3
U1 9
U2 25
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0009-2665
EI 1520-6890
J9 CHEM REV
JI Chem. Rev.
PD JUN 8
PY 2016
VL 116
IS 11
SI SI
BP 6305
EP 6322
DI 10.1021/acs.chemrev.5b00592
PG 18
WC Chemistry, Multidisciplinary
SC Chemistry
GA DO2WK
UT WOS:000377641500003
PM 26739383
ER
PT J
AU Papaleo, E
Saladino, G
Lambrughi, M
Lindorff-Larsen, K
Gervasio, FL
Nussinov, R
AF Papaleo, Elena
Saladino, Giorgio
Lambrughi, Matteo
Lindorff-Larsen, Kresten
Gervasio, Francesco Luigi
Nussinov, Ruth
TI The Role of Protein Loops and Linkers in Conformational Dynamics and
Allostery
SO CHEMICAL REVIEWS
LA English
DT Review
ID ELASTIC-NETWORK MODEL; FREE-ENERGY LANDSCAPE; UBIQUITIN-CONJUGATING
ENZYMES; EXCHANGE MOLECULAR-DYNAMICS; X-RAY SCATTERING;
YARROWIA-LIPOLYTICA LIPASE; CELL-REGULATORY SYSTEMS; MALTOSE-BINDING
PROTEIN; MECHANICS FORCE-FIELDS; GROWTH-FACTOR RECEPTOR
AB Proteins are dynamic entities that undergo a plethora of conformational changes that may take place on a wide range of time scales. These changes can be as small as the rotation of one or a few side-chain dihedral angles or involve concerted motions in larger portions of the three-dimensional structure; both kinds of motions can be important for biological function and allostery. It is becoming increasingly evident that "connector regions" are important components of the dynamic personality of protein structures. These regions may be either disordered loops, i.e., poorly structured regions connecting secondary structural elements, or linkers that connect entire protein domains. Experimental and computational studies have, however, revealed that these regions are not mere connectors, and their role in allostery and conformational changes has been emerging in the last few decades. Here we provide a detailed overview of the structural properties and classification of loops and linkers, as well as a discussion of the main computational methods employed to investigate their function and dynamical properties. We also describe their importance for protein dynamics and allostery using as examples key proteins in cellular biology and human diseases such as kinases, ubiquitinating enzymes, and transcription factors.
C1 [Papaleo, Elena] Danish Canc Soc Res Ctr, Unit Stat Bioinformat & Registry, Computat Biol Lab, Strandboulevarden 49, DK-2100 Copenhagen, Denmark.
[Papaleo, Elena; Lindorff-Larsen, Kresten] Univ Copenhagen, Dept Biol, Struct Biol & NMR Lab, DK-2200 Copenhagen, Denmark.
[Saladino, Giorgio; Gervasio, Francesco Luigi] UCL, Dept Chem, Mortimer St, London WC1E 6BT, England.
[Lambrughi, Matteo] Univ Milano Bicocca, Dept Biotechnol & Biosci, Piazza Sci 2, I-20126 Milan, Italy.
[Nussinov, Ruth] NCI, Canc & Inflammat Program, Biomed Res Inc, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
[Nussinov, Ruth] Tel Aviv Univ, Sackler Sch Med, Sackler Inst Mol Med, Dept Human Genet & Mol Med, IL-69978 Tel Aviv, Israel.
RP Papaleo, E (reprint author), Danish Canc Soc Res Ctr, Unit Stat Bioinformat & Registry, Computat Biol Lab, Strandboulevarden 49, DK-2100 Copenhagen, Denmark.; Papaleo, E (reprint author), Univ Copenhagen, Dept Biol, Struct Biol & NMR Lab, DK-2200 Copenhagen, Denmark.
EM elenap@cancer.dk
RI Lindorff-Larsen, Kresten/K-6469-2014;
OI Lindorff-Larsen, Kresten/0000-0002-4750-6039; Saladino,
Giorgio/0000-0002-3234-5762
FU National Cancer Institute, National Institutes of Health
[HHSN261200800001E]; Intramural Research Program of the NIH, National
Cancer Institute, Center for Cancer Research; Hallas-Moller grant from
the Novo Nordisk Foundation; PRACE; Danish Council for Independent
Research; Carlsberg Foundation; Velux Foundations; Lundbeck Foundation;
EPSRC [EP/M013898/1]; DyNet PRACE-3IP Project [DECI-11]; ISCRA CINECA
HPC Grants
FX This project has been funded in part with federal funds from the
National Cancer Institute, National Institutes of Health, under Contract
no. HHSN261200800001E to RN. The content of this publication does not
necessarily reflect the views or policies of the Department of Health
and Human Services, nor does mention of trade names, commercial
products, or organizations imply endorsement by the U.S. Government.
This research was supported (in part) by the Intramural Research Program
of the NIH, National Cancer Institute, Center for Cancer Research to RN.
K.L.-L. was supported by a Hallas-Moller grant from the Novo Nordisk
Foundation, and K.L.-L. acknowledges further support from PRACE, the
Danish Council for Independent Research, the Carlsberg Foundation, Velux
Foundations, and Lundbeck Foundation. F.L.G. and G.S. acknowledge
support from EPSRC [Grant EP/M013898/1]. E.P. has been supported by
DECI-11 DyNet PRACE-3IP Project and several ISCRA CINECA HPC Grants.
NR 377
TC 12
Z9 12
U1 24
U2 46
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0009-2665
EI 1520-6890
J9 CHEM REV
JI Chem. Rev.
PD JUN 8
PY 2016
VL 116
IS 11
SI SI
BP 6391
EP 6423
DI 10.1021/acs.chemrev.5b00623
PG 33
WC Chemistry, Multidisciplinary
SC Chemistry
GA DO2WK
UT WOS:000377641500006
PM 26889708
ER
PT J
AU Wei, GH
Xi, WH
Nussinov, R
Ma, BY
AF Wei, Guanghong
Xi, Wenhui
Nussinov, Ruth
Ma, Buyong
TI Protein Ensembles: How Does Nature Harness Thermodynamic Fluctuations
for Life? The Diverse Functional Roles of Conformational Ensembles in
the Cell
SO CHEMICAL REVIEWS
LA English
DT Review
ID INTRINSICALLY DISORDERED PROTEINS; FREE-ENERGY LANDSCAPE;
MOLECULAR-DYNAMICS SIMULATIONS; ALPHA-B-CRYSTALLIN; X-RAY-SCATTERING;
NUCLEAR-MAGNETIC-RESONANCE; ELONGATION-FACTOR G; STRUCTURALLY CONSERVED
RESIDUES; PURINE NUCLEOSIDE PHOSPHORYLASE; ENTHALPY-ENTROPY COMPENSATION
AB All soluble proteins populate conformational ensembles that together constitute the native state. Their fluctuations in water are intrinsic thermodynamic phenomena, and the distributions of the states on the energy landscape are determined by statistical thermodynamics; however, they are optimized to perform their biological functions. In this review we briefly describe advances in free energy landscape studies of protein conformational ensembles. Experimental (nuclear magnetic resonance; small angle X-ray scattering, single-molecule spectroscopy, and cryo-electron microscopy) and computational (replica-exchange molecular dynamics, metadynamics; and Markov state models) approaches have made great progress in recent years. These address the challenging characterization of the highly flexible and heterogeneous protein ensembles. We focus on structural aspects of protein conformational distributions, from collective motions of single- and multi-domain proteins, intrinsically disordered proteins, to multiprotein complexes. Importantly, we highlight recent studies that illustrate functional adjustment of protein conformational ensembles in the crowded cellular environment. We center on the role of the ensemble in recognition of small- and macro-molecules (protein and RNA/DNA) and emphasize emerging concepts of protein dynamics in enzyme catalysis. Overall, protein ensembles link fundamental physicochemical principles and protein behavior and the cellular network and its regulation.
C1 [Wei, Guanghong; Xi, Wenhui] Fudan Univ, Key Lab Computat Phys Sci MOE, State Key Lab Surface Phys, Shanghai 200433, Peoples R China.
[Wei, Guanghong; Xi, Wenhui] Fudan Univ, Dept Phys, Shanghai 200433, Peoples R China.
[Nussinov, Ruth; Ma, Buyong] NCI, Basic Sci Program, Leidos Biomed Res Inc, Canc & Inflammat Program, Frederick, MD 21702 USA.
[Nussinov, Ruth] Tel Aviv Univ, Sackler Sch Med, Sackler Inst Mol Med, Dept Human Genet & Mol Med, IL-69978 Tel Aviv, Israel.
RP Wei, GH (reprint author), Fudan Univ, Key Lab Computat Phys Sci MOE, State Key Lab Surface Phys, Shanghai 200433, Peoples R China.; Wei, GH (reprint author), Fudan Univ, Dept Phys, Shanghai 200433, Peoples R China.; Ma, BY (reprint author), NCI, Basic Sci Program, Leidos Biomed Res Inc, Canc & Inflammat Program, Frederick, MD 21702 USA.
EM ghwei@fudan.edu.cn; mabuyong@mail.nih.gov
RI Ma, Buyong/F-9491-2011
OI Ma, Buyong/0000-0002-7383-719X
FU Federal funds from the National Cancer Institute, National Institutes of
Health [HHSN261200800001E]; Intramural Research Program of the NIH,
National Cancer Institute, Center for Cancer Research; NSF of China
[91227102, 11274075]
FX This project has been funded in whole or in part with Federal funds from
the National Cancer Institute, National Institutes of Health, under
Contract No. HHSN261200800001E. This research was supported (in part) by
the Intramural Research Program of the NIH, National Cancer Institute,
Center for Cancer Research. G.W. acknowledges the financial support from
the NSF of China (Grant Nos. 91227102 and 11274075). We thank Wengjie
Chen for her help with the TOC figure.
NR 574
TC 18
Z9 18
U1 39
U2 76
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0009-2665
EI 1520-6890
J9 CHEM REV
JI Chem. Rev.
PD JUN 8
PY 2016
VL 116
IS 11
SI SI
BP 6516
EP 6551
DI 10.1021/acs.chemrev.5b00562
PG 36
WC Chemistry, Multidisciplinary
SC Chemistry
GA DO2WK
UT WOS:000377641500011
PM 26807783
ER
PT J
AU Lu, SY
Jang, H
Muratcioglu, S
Gursoy, A
Keskin, O
Nussinov, R
Zhang, J
AF Lu, Shaoyong
Jang, Hyunbum
Muratcioglu, Serena
Gursoy, Attila
Keskin, Ozlem
Nussinov, Ruth
Zhang, Jian
TI Ras Conformational Ensembles, Allostery, and Signaling
SO CHEMICAL REVIEWS
LA English
DT Review
ID PHOSPHOLIPASE-C-EPSILON; GUANINE-NUCLEOTIDE EXCHANGE; GTPASE-ACTIVATING
PROTEIN; ONCOGENIC K-RAS; QUANTUM MECHANICS/MOLECULAR MECHANICS;
PHOSPHOINOSITIDE 3-KINASE PATHWAY; GAP-CATALYZED-HYDROLYSIS; P-31
NMR-SPECTROSCOPY; FREE-ENERGY LANDSCAPE; H-RAS
AB Ras proteins are classical members of small GTPases that function as molecular switches by alternating between inactive GDP-bound and active GTP-bound states. Ras activation is regulated by guanine nucleotide exchange factors that catalyze the exchange of GDP by GTP, and inactivation is terminated by GTPase-activating proteins that accelerate the intrinsic GTP hydrolysis rate by orders of magnitude. In this review, we focus on data that have accumulated over the past few years pertaining to the conformational ensembles and the allosteric regulation of Ras proteins and their interpretation from our conformational landscape standpoint. The Ras ensemble embodies all states, including the ligand-bound conformations, the activated (or inactivated) allosteric modulated states, post-translationally modified states, mutational states, transition states, and nonfunctional states serving as a reservoir for emerging functions. The ensemble is shifted by distinct mutational events, cofactors, post-translational modifications, and different membrane compositions. A better understanding of Ras biology can contribute to therapeutic strategies.
C1 [Lu, Shaoyong; Zhang, Jian] Shanghai Jiao Tong Univ, Sch Med, Dept Pathophysiol,Chinese Minist Educ, Shanghai Univ E Inst Chem Biol,Key Lab Cell Diffe, Shanghai 200025, Peoples R China.
[Lu, Shaoyong; Jang, Hyunbum; Nussinov, Ruth] NCI, Canc & Inflammat Program, Leidos Biomed Res Inc, Frederick Natl Lab, Frederick, MD 21702 USA.
[Muratcioglu, Serena; Keskin, Ozlem] Koc Univ, Dept Chem & Biol Engn, Rumelifeneri Yolu, TR-34450 Sariyer, Turkey.
[Gursoy, Attila] Koc Univ, Dept Comp Engn, Rumelifeneri Yolu, TR-34450 Sariyer, Turkey.
[Nussinov, Ruth] Tel Aviv Univ, Sackler Sch Med, Sackler Inst Mol Med, Dept Human Genet & Mol Med, IL-69978 Tel Aviv, Israel.
RP Zhang, J (reprint author), Shanghai Jiao Tong Univ, Sch Med, Dept Pathophysiol,Chinese Minist Educ, Shanghai Univ E Inst Chem Biol,Key Lab Cell Diffe, Shanghai 200025, Peoples R China.; Nussinov, R (reprint author), NCI, Canc & Inflammat Program, Leidos Biomed Res Inc, Frederick Natl Lab, Frederick, MD 21702 USA.; Nussinov, R (reprint author), Tel Aviv Univ, Sackler Sch Med, Sackler Inst Mol Med, Dept Human Genet & Mol Med, IL-69978 Tel Aviv, Israel.
EM NussinoR@helix.nih.gov; jian.zhang@sjtu.edu.cn
RI Gursoy, Attila/E-9565-2015
OI Gursoy, Attila/0000-0002-2297-2113
FU National Basic Research Program of China (973 Program) [2015CB910403];
National Natural Science Foundation of China [81322046, 81302698,
81473137]; Shanghai Rising-Star Program [13QA1402300]; Program for New
Century Excellent Talents in University [NCET-12-0355]; Shanghai Health
and Family Planning Commission [20154Y0058]; Collaborative Innovation
Center of Systems Biomedicine; TUBITAK Research Grant [114M196];
Frederick National Laboratory for Cancer Research, National Institutes
of Health [HHSN261200800001E]; Intramural Research Program of NIH,
Frederick National Lab, Center for Cancer Research
FX We thank Dr. Chung-Jung Tsai for discussions. This work was supported by
National Basic Research Program of China (973 Program) (2015CB910403),
National Natural Science Foundation of China (81322046, 81302698,
81473137), Shanghai Rising-Star Program (13QA1402300), Program for New
Century Excellent Talents in University (NCET-12-0355), Shanghai Health
and Family Planning Commission (20154Y0058), and Collaborative
Innovation Center of Systems Biomedicine. This work has been partially
supported by TUBITAK Research Grant No: 114M196. This project has also
been funded in whole or in part with federal funds from the Frederick
National Laboratory for Cancer Research, National Institutes of Health,
under contract HHSN261200800001E. This research was supported (in part)
by the Intramural Research Program of NIH, Frederick National Lab,
Center for Cancer Research. The content of this publication does not
necessarily reflect the views or policies of the Department of Health
and Human Services, nor does mention of trade names, commercial products
or organizations imply endorsement by the US Government.
NR 456
TC 15
Z9 15
U1 11
U2 24
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0009-2665
EI 1520-6890
J9 CHEM REV
JI Chem. Rev.
PD JUN 8
PY 2016
VL 116
IS 11
SI SI
BP 6607
EP 6665
DI 10.1021/acs.chemrev.5b00542
PG 59
WC Chemistry, Multidisciplinary
SC Chemistry
GA DO2WK
UT WOS:000377641500014
PM 26815308
ER
PT J
AU Liu, W
Yang, RF
Payne, AS
Schowalter, RM
Spurgeon, ME
Lambert, PF
Xu, XW
Buck, CB
You, JX
AF Liu, Wei
Yang, Ruifeng
Payne, Aimee S.
Schowalter, Rachel M.
Spurgeon, Megan E.
Lambert, Paul F.
Xu, Xiaowei
Buck, Christopher B.
You, Jianxin
TI Identifying the Target Cells and Mechanisms of Merkel Cell Polyomavirus
Infection
SO CELL HOST & MICROBE
LA English
DT Article
ID EMBRYONIC STEM-CELLS; GROWTH-FACTOR; T-ANTIGENS; HUMAN SKIN; CARCINOMA;
EXPRESSION; CANCER; METALLOPROTEINASES; PROLIFERATION; INTEGRATION
AB Infection with Merkel cell polyomavirus (MCPyV) can lead to Merkel cell carcinoma (MCC), a lethal form of skin cancer. However, the skin cell type productively infected by MCPyV remains a central question. We combined cell culture and ex vivo approaches to identify human dermal fibroblasts as natural host cells that support productive MCPyV infection. Based on this, we established a cell culture model for MCPyV infection, which will facilitate investigation of the oncogenic mechanisms for this DNA virus. Using this model, we discovered that induction of matrix metalloproteinase (MMP) genes by the WNT/beta-catenin signaling pathway and other growth factors stimulates MCPyV infection. This suggests that MCC risk factors such as UV radiation and aging, which are known to stimulate WNT signaling and MMP expression, may promote viral infection and thus drive MCC. Our study also introduces the FDA-approved MEK antagonist trametinib as an effective inhibitor for controlling MCPyV infection.
C1 [Liu, Wei; You, Jianxin] Univ Penn, Dept Microbiol, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Yang, Ruifeng; Xu, Xiaowei] Univ Penn, Dept Pathol & Lab Med, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Payne, Aimee S.] Univ Penn, Dept Dermatol, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Schowalter, Rachel M.; Buck, Christopher B.] NCI, Tumor Virus Mol Biol Sect, Cellular Oncol Lab, Bethesda, MD 20892 USA.
[Spurgeon, Megan E.; Lambert, Paul F.] Univ Wisconsin, McArdle Lab Canc Res, Dept Oncol, Sch Med & Publ Hlth, 1400 Univ Ave, Madison, WI 53706 USA.
RP You, JX (reprint author), Univ Penn, Dept Microbiol, Perelman Sch Med, Philadelphia, PA 19104 USA.
EM jianyou@mail.med.upenn.edu
FU National Institutes of Health (NIH) [R01CA148768, R01CA142723,
R01CA187718]; NIAMS [AR064220, R01AR054593, P50CA174523]; Intramural
Research Program of the NIH, National Cancer Institute, Center for
Cancer Research
FX The authors would like to thank Dr. Meenhard Herlyn (Wistar Institute)
for skin cell marker antibodies, Dr. M. Celeste Simon (University of
Pennsylvania) for providing TOF-flash and FOP-flash plasmids, Dr. Ling
Li for technical support, and Margo MacDonald for editing the
manuscript. We also thank the members of our laboratories for helpful
discussion. This work was supported by the National Institutes of Health
(NIH) grants R01CA148768, R01CA142723, R01CA187718, NIAMS AR064220,
R01AR054593, and P50CA174523 and by the Intramural Research Program of
the NIH, National Cancer Institute, Center for Cancer Research.
NR 45
TC 5
Z9 5
U1 3
U2 4
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1931-3128
EI 1934-6069
J9 CELL HOST MICROBE
JI Cell Host Microbe
PD JUN 8
PY 2016
VL 19
IS 6
BP 775
EP 787
DI 10.1016/j.chom.2016.04.024
PG 13
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA DO0CM
UT WOS:000377447000009
PM 27212661
ER
PT J
AU Dunand, CJH
Leon, PE
Huang, M
Choi, A
Chromikova, V
Ho, IY
Tan, GS
Cruz, J
Hirsh, A
Zheng, NY
Mullarkey, CE
Ennis, FA
Terajima, M
Treanor, JJ
Topham, DJ
Subbarao, K
Palese, P
Krammer, F
Wilson, PC
AF Dunand, Carole J. Henry
Leon, Paul E.
Huang, Min
Choi, Angela
Chromikova, Veronika
Ho, Irvin Y.
Tan, Gene S.
Cruz, John
Hirsh, Ariana
Zheng, Nai-Ying
Mullarkey, Caitlin E.
Ennis, Francis A.
Terajima, Masanori
Treanor, John J.
Topham, David J.
Subbarao, Kanta
Palese, Peter
Krammer, Florian
Wilson, Patrick C.
TI Both Neutralizing and Non-Neutralizing Human H7N9 Influenza
Vaccine-Induced Monoclonal Antibodies Confer Protection
SO CELL HOST & MICROBE
LA English
DT Article
ID DEPENDENT CELLULAR CYTOTOXICITY; VIRUS-VACCINE; A VIRUSES; IN-VIVO;
HEALTHY-ADULTS; CLINICAL-TRIAL; HEMAGGLUTININ; RESPONSES; INFECTION;
DOMAIN
AB Pathogenic H7N9 avian influenza viruses continue to represent a public health concern, and several candidate vaccines are currently being developed. It is vital to assess if protective antibodies are induced following vaccination and to characterize the diversity of epitopes targeted. Here we characterized the binding and functional properties of twelve H7-reactive human antibodies induced by a candidate A/Anhui/1/2013 (H7N9) vaccine. Both neutralizing and non-neutralizing antibodies protected mice in vivo during passive transfer challenge experiments. Mapping the H7 hemagglutinin antigenic sites by generating escape mutant variants against the neutralizing antibodies identified unique epitopes on the head and stalk domains. Further, the broadly cross-reactive non-neutralizing antibodies generated in this study were protective through Fc-mediated effector cell recruitment. These findings reveal important properties of vaccine-induced antibodies and provide a better understanding of the human monoclonal antibody response to influenza in the context of vaccines.
C1 [Dunand, Carole J. Henry; Huang, Min; Ho, Irvin Y.; Zheng, Nai-Ying; Wilson, Patrick C.] Univ Chicago, Dept Med, Rheumatol Sect, Knapp Ctr Lupus & Immunol Res, 5841 S Maryland Ave, Chicago, IL 60637 USA.
[Leon, Paul E.; Choi, Angela; Chromikova, Veronika; Tan, Gene S.; Hirsh, Ariana; Mullarkey, Caitlin E.; Palese, Peter; Krammer, Florian] Icahn Sch Med Mt Sinai, Dept Microbiol, New York, NY 10029 USA.
[Leon, Paul E.; Choi, Angela] Icahn Sch Med Mt Sinai, Grad Sch Biomed Sci, New York, NY 10029 USA.
[Cruz, John] Univ Massachusetts, Sch Med, Dept Pathol, Worcester, MA 01655 USA.
[Ennis, Francis A.; Terajima, Masanori] Univ Massachusetts, Sch Med, Dept Med, Div Infect Dis & Immunol, Worcester, MA 01655 USA.
[Treanor, John J.] Univ Rochester, Sch Med & Dent, Dept Med, Div Infect Dis, Rochester, NY 14642 USA.
[Topham, David J.] Univ Rochester, Sch Med & Dent, Dept Microbiol & Immunol, Ctr Vaccine Biol & Immunol, Rochester, NY 14642 USA.
[Subbarao, Kanta] NIAID, Infect Dis Lab, NIH, Rockville, MD 20852 USA.
[Palese, Peter] Icahn Sch Med Mt Sinai, Dept Med, New York, NY 10029 USA.
RP Wilson, PC (reprint author), Univ Chicago, Dept Med, Rheumatol Sect, Knapp Ctr Lupus & Immunol Res, 5841 S Maryland Ave, Chicago, IL 60637 USA.; Krammer, F (reprint author), Icahn Sch Med Mt Sinai, Dept Microbiol, New York, NY 10029 USA.
EM florian.krammer@mssm.edu; wilsonp@uchicago.edu
OI Palese, Peter/0000-0002-0337-5823; Krammer, Florian/0000-0003-4121-776X
FU National Institute of Allergy and Infectious Diseases, NIH, Department
of Health and Human Services, under CEIRS contracts [HHSN272201400006C,
HHSN272201400008C]; NIH [U19AI109946-01, P01AI097092-03,
P01AI097092-04S1, U19AI057266-11]; Division of Intramural Research,
NIAID, NIH; Biomedical Advanced Research and Development Authority, HHS
[HHSN272200900026C]
FX This project has been funded in part with federal funds from the
National Institute of Allergy and Infectious Diseases, NIH, Department
of Health and Human Services, under CEIRS contracts No HHSN272201400006C
(P.C.W., J.J.T., and D.J.T.) and HHSN272201400008C (P.P. and F.K.); NIH
U19AI109946-01 (P.C.W., P.P., and F.K.), P01AI097092-03 (P.C.W. and
P.P.), P01AI097092-04S1 (P.E.L.), and U19AI057266-11 (P.C.W.). Clinical
trial NCT01995695 was supported by the Division of Intramural Research,
NIAID, NIH and by the Biomedical Advanced Research and Development
Authority, HHS, under contract #HHSN272200900026C. We thank Donna Neu,
Mary Dawn T. Co, the Center for Therapeutic Antibody Development, the
Flow Cytometry Center of Research Excellence, and the Microscopy Core at
the Icahn School of Medicine at Mount Sinai and the University of
Chicago Flow Cytometry Core.
NR 54
TC 12
Z9 12
U1 2
U2 3
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1931-3128
EI 1934-6069
J9 CELL HOST MICROBE
JI Cell Host Microbe
PD JUN 8
PY 2016
VL 19
IS 6
BP 800
EP 813
DI 10.1016/j.chom.2016.05.014
PG 14
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA DO0CM
UT WOS:000377447000011
ER
PT J
AU Grant, A
Ponia, SS
Tripathi, S
Balasubramaniam, V
Miorin, L
Sourisseau, M
Schwarz, MC
Sanchez-Seco, MP
Evans, MJ
Best, SM
Garcia-Sastre, A
AF Grant, Alesha
Ponia, Sanket S.
Tripathi, Shashank
Balasubramaniam, Vinod
Miorin, Lisa
Sourisseau, Marion
Schwarz, Megan C.
Paz Sanchez-Seco, Mari
Evans, Matthew J.
Best, Sonja M.
Garcia-Sastre, Adolfo
TI Zika Virus Targets Human STAT2 to Inhibit Type I Interferon Signaling
SO CELL HOST & MICROBE
LA English
DT Article
ID WEST-NILE-VIRUS; DENGUE VIRUS; NS5 PROTEIN; ANTAGONIST; FLAVIVIRUS;
IDENTIFICATION; ACTIVATION; MECHANISMS; HEMISPHERE; EMERGENCE
AB The ongoing epidemic of Zika virus (ZIKV) illustrates the importance of flaviviruses as emerging human pathogens. All vector-borne flaviviruses studied thus far have to overcome type I interferon (IFN) to replicate and cause disease in vertebrates. The mechanism(s) by which ZIKV antagonizes IFN signaling is unknown. Here, we report that the nonstructural protein NS5 of ZIKV and other flaviviruses examined could suppress IFN signaling, but through different mechanisms. ZIKV NS5 expression resulted in proteasomal degradation of the IFN-regulated transcriptional activator STAT2 from humans, but not mice, which may explain the requirement for IFN deficiency to observe ZIKV-induced disease in mice. The mechanism of ZIKV NS5 resembles dengue virus (DENV) NS5 and not its closer relative, Spondweni virus (SPOV). However, unlike DENV, ZIKV did not require the E3 ubiquitin ligase UBR4 to induce STAT2 degradation. Hence, flavivirus NS5 proteins exhibit a remarkable functional convergence in IFN antagonism, albeit by virus-specific mechanisms.
C1 [Grant, Alesha; Tripathi, Shashank; Balasubramaniam, Vinod; Miorin, Lisa; Sourisseau, Marion; Schwarz, Megan C.; Evans, Matthew J.; Garcia-Sastre, Adolfo] Icahn Sch Med Mt Sinai, Dept Microbiol, New York, NY 10029 USA.
[Grant, Alesha; Tripathi, Shashank; Balasubramaniam, Vinod; Miorin, Lisa; Garcia-Sastre, Adolfo] Icahn Sch Med Mt Sinai, Global Hlth & Emerging Pathogens Inst, New York, NY 10029 USA.
[Ponia, Sanket S.; Best, Sonja M.] NIAID, Virol Lab, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA.
[Paz Sanchez-Seco, Mari] Inst Hlth Carlos III, Natl Ctr Microbiol, Lab Arbovirus & Imported Viral Dis, Madrid 28029, Spain.
[Garcia-Sastre, Adolfo] Icahn Sch Med Mt Sinai, Dept Med, Div Infect Dis, New York, NY 10029 USA.
RP Garcia-Sastre, A (reprint author), Icahn Sch Med Mt Sinai, Dept Microbiol, New York, NY 10029 USA.; Garcia-Sastre, A (reprint author), Icahn Sch Med Mt Sinai, Global Hlth & Emerging Pathogens Inst, New York, NY 10029 USA.; Garcia-Sastre, A (reprint author), Icahn Sch Med Mt Sinai, Dept Med, Div Infect Dis, New York, NY 10029 USA.
EM adolfo.garcia-sastre@mssm.edu
RI RMT Balasubramaniam, Vinod/B-6957-2017;
OI RMT Balasubramaniam, Vinod/0000-0001-9583-307X; Evans,
Matthew/0000-0002-4991-3877; Garcia-Sastre, Adolfo/0000-0002-6551-1827
FU Intramural Research Program of the NIH, National Institute of Allergy
and Infectious Diseases; [U19AI118610]
FX We thank Barbara W. Johnson, Ana Fernandez-Sesma, and Steve Whitehead
for kindly providing the 2015 PR ZIKV, 16881 DENV2, and 2015 Fortaleza
ZIKV strains, respectively. We thank Genhong Cheng for
IFNAR1-/- MEFs. We thank the microscopy and FACS SRF at Icahn
School of Medicine for their support and Richard Cadagan for excellent
technical assistance. This work was supported in part by the Intramural
Research Program of the NIH, National Institute of Allergy and
Infectious Diseases. These studies were also partly supported by a
supplement to NIAID grant U19AI118610.
NR 44
TC 32
Z9 32
U1 21
U2 45
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1931-3128
EI 1934-6069
J9 CELL HOST MICROBE
JI Cell Host Microbe
PD JUN 8
PY 2016
VL 19
IS 6
BP 882
EP 890
DI 10.1016/j.chom.2016.05.009
PG 9
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA DO0CM
UT WOS:000377447000018
PM 27212660
ER
PT J
AU Guzman, DA
Pellegrini, S
Flesia, AG
Aon, MA
Marin, RH
Kembro, JM
AF Guzman, Diego A.
Pellegrini, Stefania
Flesia, Ana G.
Aon, Miguel A.
Marin, Raul H.
Kembro, Jackelyn M.
TI High resolution, week-long, locomotion time series from Japanese quail
in a home-box environment
SO SCIENTIFIC DATA
LA English
DT Article; Data Paper
ID BEHAVIORAL RHYTHMS; HUMAN GAIT; DYNAMICS; FLUCTUATIONS; WALKING; HENS
AB Temporal and spatial patterns of locomotion reflect both resting periods and the movement from one place to another to satisfy physiological and behavioural needs. Locomotion is studied in diverse areas of biology such as chronobiology and physiology, as well as in biomathematics. Herein, the locomotion of 24 visually-isolated Japanese quails in their home-box environment was recorded continuously over a 6.5 days at a 0.5 s sampling rate. Three time series are presented for each bird: (1) locomotor activity, (2) distance ambulated, and (3) zone of the box where the bird is located. These high resolution, week-long, time series consisting of 1.07 x 10(6) data points represent, to our knowledge, a unique data set in animal behavior, and are publically available on FigShare. The data obtained can be used for analyzing dynamic changes of daily or several day locomotion patterns, or for comparison with existing or future data sets or mathematical models across different taxa.
C1 [Guzman, Diego A.; Pellegrini, Stefania; Marin, Raul H.; Kembro, Jackelyn M.] Univ Nacl Cordoba, Fac Ciencias Exactas Fis & Nat, CONICET, IIByT, Catedra Quim Biol,1611 Velez Sarsfield,X5016GCA, Cordoba, Argentina.
[Guzman, Diego A.; Pellegrini, Stefania; Marin, Raul H.; Kembro, Jackelyn M.] Univ Nacl Cordoba, Fac Ciencias Exactas Fis & Nat, Inst Ciencia & Tecnol Alimentos, Catedra Quim Biol,1611 Velez Sarsfield,X5016GCA, Cordoba, Argentina.
[Guzman, Diego A.] Aarhus Univ, Dept Anim Sci, 20 Blichers Alle,Post Box 50, DK-8830 Tjele, Denmark.
[Flesia, Ana G.] Univ Nacl Cordoba, CONICET, CIEM, Ingn Medina Allende S-N Ciudad Univ,CP X5000HUA, Cordoba, Argentina.
[Flesia, Ana G.] Univ Nacl Cordoba, Fac Matemat Astron & Fis FAMAF, Ingn Medina Allende S-N Ciudad Univ,CP X5000HUA, Cordoba, Argentina.
[Aon, Miguel A.] Johns Hopkins Univ, Sch Med, Baltimore, MD 21205 USA.
[Aon, Miguel A.] NIA, NIH, BRC BG Rm 09B119,251 Bayview Blvd, Baltimore, MD 21224 USA.
RP Kembro, JM (reprint author), Univ Nacl Cordoba, Fac Ciencias Exactas Fis & Nat, CONICET, IIByT, Catedra Quim Biol,1611 Velez Sarsfield,X5016GCA, Cordoba, Argentina.; Kembro, JM (reprint author), Univ Nacl Cordoba, Fac Ciencias Exactas Fis & Nat, Inst Ciencia & Tecnol Alimentos, Catedra Quim Biol,1611 Velez Sarsfield,X5016GCA, Cordoba, Argentina.
EM jkembro@efn.uncor.edu
RI Aon, Miguel/A-6564-2008;
OI Aon, Miguel/0000-0002-4355-5431; Flesia, Ana
Georgina/0000-0001-6936-3764
NR 30
TC 1
Z9 1
U1 1
U2 1
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2052-4463
J9 SCI DATA
JI Sci. Data
PD JUN 7
PY 2016
VL 3
AR UNSP 160036
DI 10.1038/sdata.2016.36
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EF3IK
UT WOS:000390217800001
PM 27271772
ER
PT J
AU Zook, JM
Catoe, D
McDaniel, J
Vang, L
Spies, N
Sidow, A
Weng, ZM
Liu, YL
Mason, CE
Alexander, N
Henaff, E
McIntyre, ABR
Chandramohan, D
Chen, F
Jaeger, E
Moshrefi, A
Pham, K
Stedman, W
Liang, T
Saghbini, M
Dzakula, Z
Hastie, A
Cao, H
Deikus, G
Schadt, E
Sebra, R
Bashir, A
Truty, RM
Chang, CC
Gulbahce, N
Zhao, KY
Ghosh, S
Hyland, F
Fu, YT
Chaisson, M
Xiao, CL
Trow, J
Sherry, ST
Zaranek, AW
Ball, M
Bobe, J
Estep, P
Church, GM
Marks, P
Kyriazopoulou-Panagiotopoulou, S
Zheng, GXY
Schnall-Levin, M
Ordonez, HS
Mudivarti, PA
Giorda, K
Sheng, Y
Rypdal, KB
Salit, M
AF Zook, Justin M.
Catoe, David
McDaniel, Jennifer
Vang, Lindsay
Spies, Noah
Sidow, Arend
Weng, Ziming
Liu, Yuling
Mason, Christopher E.
Alexander, Noah
Henaff, Elizabeth
McIntyre, Alexa B. R.
Chandramohan, Dhruva
Chen, Feng
Jaeger, Erich
Moshrefi, Ali
Khoa Pham
Stedman, William
Liang, Tiffany
Saghbini, Michael
Dzakula, Zeljko
Hastie, Alex
Cao, Han
Deikus, Gintaras
Schadt, Eric
Sebra, Robert
Bashir, Ali
Truty, Rebecca M.
Chang, Christopher C.
Gulbahce, Natali
Zhao, Keyan
Ghosh, Srinka
Hyland, Fiona
Fu, Yutao
Chaisson, Mark
Xiao, Chunlin
Trow, Jonathan
Sherry, Stephen T.
Zaranek, Alexander W.
Ball, Madeleine
Bobe, Jason
Estep, Preston
Church, George M.
Marks, Patrick
Kyriazopoulou-Panagiotopoulou, Sofia
Zheng, Grace X. Y.
Schnall-Levin, Michael
Ordonez, Heather S.
Mudivarti, Patrice A.
Giorda, Kristina
Sheng, Ying
Rypdal, Karoline Bjarnesdatter
Salit, Marc
TI Extensive sequencing of seven human genomes to characterize benchmark
reference materials
SO SCIENTIFIC DATA
LA English
DT Article
ID FRAMEWORK; READS
AB The Genome in a Bottle Consortium, hosted by the National Institute of Standards and Technology (NIST) is creating reference materials and data for human genome sequencing, as well as methods for genome comparison and benchmarking. Here, we describe a large, diverse set of sequencing data for seven human genomes; five are current or candidate NIST Reference Materials. The pilot genome, NA12878, has been released as NIST RM 8398. We also describe data from two Personal Genome Project trios, one of Ashkenazim Jewish ancestry and one of Chinese ancestry. The data come from 12 technologies: BioNano Genomics, Complete Genomics paired-end and LFR, Ion Proton exome, Oxford Nanopore, Pacific Biosciences, SOLiD, 10X Genomics GemCode WGS, and Illumina exome and WGS paired-end, mate-pair, and synthetic long reads. Cell lines, DNA, and data from these individuals are publicly available. Therefore, we expect these data to be useful for revealing novel information about the human genome and improving sequencing technologies, SNP, indel, and structural variant calling, and de novo assembly.
C1 [Zook, Justin M.; Catoe, David; McDaniel, Jennifer; Vang, Lindsay; Spies, Noah; Salit, Marc] NIST, Gaithersburg, MD 20899 USA.
[Spies, Noah; Sidow, Arend; Weng, Ziming; Liu, Yuling; Salit, Marc] Stanford Univ, Stanford, CA 94305 USA.
[Mason, Christopher E.; Alexander, Noah; Henaff, Elizabeth; McIntyre, Alexa B. R.; Chandramohan, Dhruva] Cornell Univ, Weill Med Coll, Dept Physiol & Biophys, Feil Family Brain & Mind Res Inst, New York, NY 10065 USA.
[Mason, Christopher E.; Alexander, Noah; Henaff, Elizabeth; McIntyre, Alexa B. R.; Chandramohan, Dhruva] Cornell Univ, Weill Med Coll, HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsau, New York, NY 10065 USA.
[Chen, Feng; Jaeger, Erich; Moshrefi, Ali] Illumina Mission Bay, San Francisco, CA 94158 USA.
[Khoa Pham; Stedman, William; Liang, Tiffany; Saghbini, Michael; Dzakula, Zeljko; Hastie, Alex; Cao, Han] BioNano Genom, San Diego, CA 92121 USA.
[Deikus, Gintaras; Schadt, Eric; Sebra, Robert; Bashir, Ali; Bobe, Jason] Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, New York, NY 10029 USA.
[Truty, Rebecca M.; Chang, Christopher C.; Gulbahce, Natali] Complete Genom Inc, Mountain View, CA 94043 USA.
[Zhao, Keyan; Ghosh, Srinka; Hyland, Fiona; Fu, Yutao] Thermo Fisher Sci, San Francisco, CA 94080 USA.
[Chaisson, Mark] Univ Washington, Genome Sci, Seattle, WA 98105 USA.
[Xiao, Chunlin; Trow, Jonathan] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, 45 Ctr Dr, Bethesda, MD 20892 USA.
[Zaranek, Alexander W.; Ball, Madeleine; Bobe, Jason; Estep, Preston; Church, George M.] PersonalGenomes Org, Boston, MA 02115 USA.
[Estep, Preston; Church, George M.] Harvard Med Sch, Boston, MA 02115 USA.
[Marks, Patrick; Kyriazopoulou-Panagiotopoulou, Sofia; Zheng, Grace X. Y.; Schnall-Levin, Michael; Ordonez, Heather S.; Mudivarti, Patrice A.; Giorda, Kristina] 10X Genom, Pleasanton, CA 94566 USA.
[Sheng, Ying; Rypdal, Karoline Bjarnesdatter] Oslo Univ Hosp, Dept Med Genet, Kirkeveien 166,Bygg 25, N-0450 Oslo, Norway.
RP Zook, JM (reprint author), NIST, Gaithersburg, MD 20899 USA.
EM jzook@nist.gov
FU Starr Cancer Consortium [I4-A442, I7-A765, I9-A9-071]; Irma T. Hirschl
Trust; Monique Weill-Caulier Charitable Trust; Bert L and N Kuggie
Vallee Foundation; WorldQuant Foundation; Pershing Square Sohn Cancer
Research Alliance; NASA [NNX14AH50G]; National Institutes of Health
[R25EB020393, R01NS076465]
FX We thank members of the Genome in a Bottle Consortium for their feedback
before and during this study. C.E.M. acknowledges funding from the Starr
Cancer Consortium grant I4-A442, I7-A765, I9-A9-071), the Irma T.
Hirschl and Monique Weill-Caulier Charitable Trusts, Bert L and N Kuggie
Vallee Foundation and the WorldQuant Foundation (CEM), The Pershing
Square Sohn Cancer Research Alliance, NASA (NNX14AH50G), and the
National Institutes of Health (R25EB020393, R01NS076465). Certain
commercial equipment, instruments, or materials are identified in this
paper only to specify the experimental procedure adequately. Such
identification is not intended to imply recommendation or endorsement by
the NIST, nor is it intended to imply that the materials or equipment
identified are necessarily the best available for the purpose.
NR 30
TC 2
Z9 2
U1 2
U2 2
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2052-4463
J9 SCI DATA
JI Sci. Data
PD JUN 7
PY 2016
VL 3
AR UNSP 160025
DI 10.1038/sdata.2016.25
PG 26
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EF3IE
UT WOS:000390217200001
PM 27271295
ER
PT J
AU Robinson, OJ
Krimsky, M
Lieberman, L
Vytal, K
Ernst, M
Grillon, C
AF Robinson, O. J.
Krimsky, M.
Lieberman, L.
Vytal, K.
Ernst, M.
Grillon, C.
TI Anxiety-potentiated amygdala-medial frontal coupling and attentional
control
SO TRANSLATIONAL PSYCHIATRY
LA English
DT Article
ID AVERSIVE AMPLIFICATION CIRCUIT; DORSOMEDIAL PREFRONTAL CORTEX;
COGNITIVE-BEHAVIORAL THERAPY; ANTERIOR CINGULATE; EMOTION REGULATION;
THREAT; DISORDERS; MODULATION; CONTEXT; BIAS
AB Anxiety disorders can be treated both pharmacologically and psychologically, but many individuals either fail to respond to treatment or relapse. Improving outcomes is difficult, in part because we have incomplete understanding of the neurobiological mechanisms underlying current treatments. In a sequence of studies, we have identified 'affective bias-related' amygdala-medial cortical coupling as a candidate substrate underlying adaptive anxiety (that is, anxiety elicited by threat of shock in healthy individuals) and shown that it is also chronically engaged in maladaptive anxiety disorders. We have provided evidence that this circuit can be modulated pharmacologically, but whether this mechanism can be shifted by simple psychological instruction is unknown. In this functional magnetic resonance imaging study, we extend a previously used translational anxiety induction (threat of shock) in healthy subjects (N = 43) and cognitive task to include an element of instructed attentional control. Replicating our previous findings, we show that induced anxiety engages 'affective bias-related' amygdala-dorsal medial frontal coupling during the processing of emotional faces. By contrast, instructing subjects to attend to neutral shapes (and ignore faces) disengages this circuitry and increases putative 'attentional control-related' coupling between the amygdala and a more rostral prefrontal region. These neural coupling changes are accompanied by corresponding modulation of behavioural performance. Taken together, these findings serve to further highlight the potential role of amygdala-medial frontal coupling in the pathogenesis of anxiety and highlight a mechanism by which it can be modulated via psychological instructions. This, in turn, generates hypotheses for future work exploring the mechanisms underlying psychological therapeutic interventions for anxiety.
C1 [Robinson, O. J.] UCL, Inst Cognit Neurosci, Alexandra House,Queen Sq, London WC1N 3AR, England.
[Robinson, O. J.; Krimsky, M.; Lieberman, L.; Vytal, K.; Ernst, M.; Grillon, C.] NIMH, Sect Neurobiol Fear & Anxiety, NIH, Bethesda, MD 20892 USA.
RP Robinson, OJ (reprint author), UCL, Inst Cognit Neurosci, Alexandra House,Queen Sq, London WC1N 3AR, England.
EM oliver.j.robinson@gmail.com
FU National Institutes of Health; Medical Research Council [MR/K024280/1]
FX This work was funded by the intramural programme of the National
Institutes of Health and an individual Medical Research Council Career
Development Award Fellowship to OJR (MR/K024280/1).
NR 39
TC 3
Z9 3
U1 4
U2 6
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 2158-3188
J9 TRANSL PSYCHIAT
JI Transl. Psychiatr.
PD JUN 7
PY 2016
VL 6
AR e833
DI 10.1038/tp.2016.105
PG 6
WC Psychiatry
SC Psychiatry
GA DW1QE
UT WOS:000383416900005
PM 27271859
ER
PT J
AU Li, SX
Ren, LQ
Huang, PH
Yao, XL
Cuento, RA
McCoy, JP
Cameron, CE
Levine, SJ
Huang, TJ
AF Li, Sixing
Ren, Liqian
Huang, Po-Hsun
Yao, Xianglan
Cuento, Rosemarie A.
McCoy, J. Philip
Cameron, Craig E.
Levine, Stewart J.
Huang, Tony Jun
TI Acoustofluidic Transfer of Inflammatory Cells from Human Sputum Samples
SO ANALYTICAL CHEMISTRY
LA English
DT Article
ID SURFACE ACOUSTIC-WAVES; CARRIER-MEDIUM EXCHANGE; CONTINUOUS-FLOW;
STANDING-WAVE; SEPARATION; PARTICLES; STREAMS; CHIP; DITHIOTHREITOL;
MANIPULATION
AB For sputum analysis, the transfer of inflammatory cells from liquefied sputum samples to a culture medium or buffer solution is a critical step because it removes the inflammatory cells from the presence of residual dithiothreitol (DTT), a reagent that reduces cell viability and interferes with further sputum analyses. In this work, we report an acoustofluidic platform for transferring inflammatory cells using standing surface acoustic waves (SSAW). In particular, we exploit the acoustic radiation force generated from a SSAW field to actively transfer inflammatory cells from a solution containing residual DTT to a buffer solution. The viability and integrity of the inflammatory cells are maintained during the acoustofluidic-based cell transfer process. Our acoustofluidic technique removes residual DTT generated in sputum liquefaction and facilitates immunophenotyping of major inflammatory cells from sputum samples. It enables cell transfer in a continuous flow, which aids the development of an automated, integrated system for on-chip sputum processing and analysis.
C1 [Li, Sixing; Ren, Liqian; Huang, Po-Hsun; Huang, Tony Jun] Penn State Univ, Dept Engn Sci & Mech, 227 Hammond Bldg, University Pk, PA 16802 USA.
[Li, Sixing; Cameron, Craig E.; Huang, Tony Jun] Penn State Univ, Mol Cellular & Integrat Biosci MCIBS Grad Program, Huck Inst Life Sci, University Pk, PA 16802 USA.
[Cameron, Craig E.] Penn State Univ, Dept Biochem & Mol Biol, University Pk, PA 16802 USA.
[Yao, Xianglan; Cuento, Rosemarie A.; McCoy, J. Philip; Levine, Stewart J.] NHLBI, NIH, Bldg 10, Bethesda, MD 20892 USA.
RP Huang, TJ (reprint author), Penn State Univ, Dept Engn Sci & Mech, 227 Hammond Bldg, University Pk, PA 16802 USA.; Huang, TJ (reprint author), Penn State Univ, Mol Cellular & Integrat Biosci MCIBS Grad Program, Huck Inst Life Sci, University Pk, PA 16802 USA.; Levine, SJ (reprint author), NHLBI, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM levines@nhlbi.nih.gov; junhuang@psu.edu
RI Huang, Po-Hsun/A-2713-2015; Li, Sixing/F-2383-2013; Huang,
Tony/A-1546-2009; Ren, Liqiang/E-8953-2015
OI Huang, Po-Hsun/0000-0001-9600-0141; Ren, Liqiang/0000-0003-0863-4609
FU American Asthma Foundation (AAF) Scholar Award; National Institutes of
Health [1R01AI120560-01]; NHLBI Division of Intramural Research; NIAID,
NIH [AI45818]; NSF
FX We thank Dr. Zhiwei Xie from Prof. Jiang Yang's group for microplate
fluorescence measurements. This research was supported by the American
Asthma Foundation (AAF) Scholar Award, National Institutes of Health
(1R01AI120560-01), and the NHLBI Division of Intramural Research. S.L.
and C.E.C. were funded in part by Grant AI45818 from NIAID, NIH.
Components of this work were conducted at the Penn State node of the
NSF-funded National Nanotechnology Infrastructure Network (NNIN).
NR 49
TC 3
Z9 3
U1 6
U2 15
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0003-2700
EI 1520-6882
J9 ANAL CHEM
JI Anal. Chem.
PD JUN 7
PY 2016
VL 88
IS 11
BP 5655
EP 5661
DI 10.1021/acs.analchem.5b03383
PG 7
WC Chemistry, Analytical
SC Chemistry
GA DO2ST
UT WOS:000377631000018
PM 27183317
ER
PT J
AU Fujii, R
Friedman, ER
Richards, J
Tsang, KY
Heery, CR
Schlom, J
Hodge, JW
AF Fujii, Rika
Friedman, Eitan R.
Richards, Jacob
Tsang, Kwong Y.
Heery, Christopher R.
Schlom, Jeffrey
Hodge, James W.
TI Enhanced killing of chordoma cells by antibody-dependent cell-mediated
cytotoxicity employing the novel anti-PD-L1 antibody avelumab
SO ONCOTARGET
LA English
DT Article
DE chordoma; programmed death-ligand 1 (PD-L1); antibody-dependent
cell-mediated cytotoxicity (ADCC); cancer stem cells; immunotherapy
ID TRANSCRIPTION FACTOR BRACHYURY; CANCER STEM-CELLS;
EPITHELIAL-MESENCHYMAL TRANSITION; DEATH-LIGAND 1; PROGRAMMED DEATH-1;
BREAST-CANCER; TUMOR-CELLS; PD-L1 EXPRESSION; NK CELLS; PHASE-I
AB Chordoma, a rare bone tumor derived from the notochord, has been shown to be resistant to conventional therapies. Checkpoint inhibition has shown great promise in immune-mediated therapy of diverse cancers. The anti-PD-L1 mAb avelumab is unique among checkpoint inhibitors in that it is a fully human IgG1 capable of mediating antibody-dependent cell-mediated cytotoxicity (ADCC) of PD-L1-expressing tumor cells. Here, we investigated avelumab as a potential therapy for chordoma. We examined 4 chordoma cell lines, first for expression of PD-L1, and in vitro for ADCC killing using NK cells and avelumab. PD-L1 expression was markedly upregulated by IFN-gamma in all 4 chordoma cell lines, which significantly increased sensitivity to ADCC. Brachyury is a transcription factor that is uniformly expressed in chordoma. Clinical trials are ongoing in which chordoma patients are treated with brachyury-specific vaccines. Co-incubating chordoma cells with brachyury-specific CD8(+) T cells resulted in significant upregulation of PD-L1 on the tumor cells, mediated by the CD8(+) T cells' IFN-gamma production, and increased sensitivity of chordoma cells to avelumab-mediated ADCC. Residential cancer stem cell subpopulations of chordoma cells were also killed by avelumab-mediated ADCC to the same degree as non-cancer stem cell populations. These findings suggest that as a monotherapy for chordoma, avelumab may enable endogenous NK cells, while in combination with T-cell immunotherapy, such as a vaccine, avelumab may enhance NK-cell killing of chordoma cells via ADCC.
C1 [Fujii, Rika; Friedman, Eitan R.; Richards, Jacob; Tsang, Kwong Y.; Heery, Christopher R.; Schlom, Jeffrey; Hodge, James W.] NCI, Lab Tumor Immunol & Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Hodge, JW (reprint author), NCI, Lab Tumor Immunol & Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM jh241d@nih.gov
RI Hodge, James/D-5518-2015
OI Hodge, James/0000-0001-5282-3154
FU Intramural Research Program of the Center for Cancer Research; National
Cancer Institute; National Institutes of Health; Emd Sereno; NCI
FX This research was supported by the Intramural Research Program of the
Center for Cancer Research, National Cancer Institute, National
Institutes of Health, as well as through a cooperative research and
development aggrement (CRADA) betwwen Emd Sereno and the NCI.
NR 55
TC 3
Z9 3
U1 5
U2 8
PU IMPACT JOURNALS LLC
PI ALBANY
PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA
SN 1949-2553
J9 ONCOTARGET
JI Oncotarget
PD JUN 7
PY 2016
VL 7
IS 23
BP 33498
EP 33511
DI 10.18632/oncotarget.9256
PG 14
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA DO4KS
UT WOS:000377752100002
PM 27172898
ER
PT J
AU Lefebvre, JS
Lorenzo, EC
Masters, AR
Hopkins, JW
Eaton, SM
Smiley, ST
Haynes, L
AF Lefebvre, Julie S.
Lorenzo, Erica C.
Masters, April R.
Hopkins, Jacob W.
Eaton, Sheri M.
Smiley, Stephen T.
Haynes, Laura
TI Vaccine efficacy and T helper cell differentiation change with aging
SO ONCOTARGET
LA English
DT Article
DE aging; influenza; Th subsets; influenza vaccination; antibody;
Gerotarget
ID INFLUENZA-VIRUS INFECTION; PLATELET-ACTIVATING-FACTOR; AGED MICE;
STREPTOCOCCUS-PNEUMONIAE; SEASONAL INFLUENZA; IMMUNE-RESPONSES; LETHAL
INFLUENZA; INNATE IMMUNITY; PROTECTION; DEFECTS
AB Influenza and pneumonia are leading causes of death in elderly populations. With age, there is an increased inflammatory response and slower viral clearance during influenza infection which increases the risk of extended illness and mortality. Here we employ a preclinical murine model of influenza infection to examine the protective capacity of vaccination with influenza nucleoprotein (NP). While NP vaccination reduces influenza-induced lung inflammation in young mice, aged mice do not show this reduction, but are protected from influenza-induced mortality. Aged mice do make a significant amount of NP-specific IgG and adoptive transfer experiments show that NP antibody can protect from death but cannot reduce lung inflammation. Furthermore, young but not aged vaccinated mice generate significant numbers of NP-specific T cells following subsequent infection and few of these T cells are found in aged lungs early during infection. Importantly, aged CD4 T cells have a propensity to differentiate towards a T follicular helper (Tfh) phenotype rather than a T helper 1 (Th1) phenotype that predominates in the young. Since Th1 cells are important in viral clearance, reduced Th1 differentiation in the aged is critical and could account for some or all of the age-related differences in vaccine responses and infection resolution.
C1 [Lefebvre, Julie S.; Eaton, Sheri M.; Smiley, Stephen T.] Trudeau Inst, Saranac Lake, NY USA.
[Lorenzo, Erica C.; Masters, April R.; Hopkins, Jacob W.; Haynes, Laura] Univ Connecticut, Ctr Hlth, Dept Immunol, Farmington, CT USA.
[Lorenzo, Erica C.; Masters, April R.; Hopkins, Jacob W.; Haynes, Laura] Univ Connecticut, Ctr Hlth, Ctr Aging, Farmington, CT USA.
[Lefebvre, Julie S.] CHU Laval, Ctr Rech, Inst Univ Cardiol & Pneumol Quebec, Dept Pneumol, 2705 Blvd Laurier, Quebec City, PQ G1V 4G2, Canada.
[Smiley, Stephen T.] NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
RP Haynes, L (reprint author), Univ Connecticut, Ctr Hlth, Dept Immunol, Farmington, CT USA.; Haynes, L (reprint author), Univ Connecticut, Ctr Hlth, Ctr Aging, Farmington, CT USA.
EM lhaynes@uchc.edu
FU NIH/NIA grant [AG02160]; Trudeau Institute; UConn Center on Aging; Fonds
de recherche du Quebec-Sante/Reseau quebecois de recherche sur le
vieillissement/NIA
FX This study was supported by NIH/NIA grant AG02160 to L.H. and funding
from the Trudeau Institute and the UConn Center on Aging. J.S.L. is the
recipient of a postdoctoral fellowship awarded jointly by the Fonds de
recherche du Quebec-Sante/Reseau quebecois de recherche sur le
vieillissement/NIA.
NR 50
TC 0
Z9 0
U1 3
U2 4
PU IMPACT JOURNALS LLC
PI ALBANY
PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA
SN 1949-2553
J9 ONCOTARGET
JI Oncotarget
PD JUN 7
PY 2016
VL 7
IS 23
BP 33581
EP 33594
DI 10.18632/oncotarget.9254
PG 14
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA DO4KS
UT WOS:000377752100008
PM 27177221
ER
PT J
AU Park, J
Kim, WG
Zhao, L
Enomoto, K
Willingham, M
Cheng, SY
AF Park, Jeongwon
Kim, Won Gu
Zhao, Li
Enomoto, Keisuke
Willingham, Mark
Cheng, Sheue-Yann
TI Metformin blocks progression of obesity-activated thyroid cancer in a
mouse model
SO ONCOTARGET
LA English
DT Article
DE thyroid carcinogenesis; obesity; metformin; mouse models
ID HIGH-FAT DIET; INHIBITS GROWTH; DIABETIC-PATIENTS; BREAST-CANCER;
CARCINOMA; MICE; RISK; RAPAMYCIN; KINASE; CELLS
AB Compelling epidemiologic evidence indicates that obesity is associated with a high risk of human malignancies, including thyroid cancer. We previously demonstrated that a high fat diet (HFD) effectively induces the obese phenotype in a mouse model of aggressive follicular thyroid cancer (Thrb(PV/PV)Pten(+/-)mice). We showed that HFD promotes cancer progression through aberrant activation of the leptin-JAK2-STAT3 signaling pathway. HFD-promoted thyroid cancer progression allowed us to test other molecular targets for therapeutic opportunity for obesity-induced thyroid cancer. Metformin is a widely used drug to treat patients with type II diabetes. It has been shown to reduce incidences of neoplastic diseases and cancer mortality in type II diabetes patients. The present study aimed to test whether metformin could be a therapeutic for obesity-activated thyroid cancer. Thrb(PV/PV)Pten(+/-)mice were fed HFD together with metformin or vehicle-only, as controls, for 20 weeks. While HFD-Thrb(PV/PV)Pten(+/-)mice had shorter survival than LFD-treated mice, metformin had no effects on the survival of HFD-Thrb(PV/PV)Pten(+/-)mice. Remarkably, metformin markedly decreased occurrence of capsular invasion and completely blocked vascular invasion and anaplasia in HFD-ThrbPV/PVPten(+/-)mice without affecting thyroid tumor growth. The impeded cancer progression was due to the inhibitory effect of metformin on STAT3-ERK-vimentin and fibronectin-integrin signaling to decrease tumor cell invasion and de-differentiation. The present studies provide additional molecular evidence to support the link between obesity and thyroid cancer risk. Importantly, our findings suggest that metformin could be used as an adjuvant in combination with antiproliferative modalities to improve the outcome of patients with obesity-activated thyroid cancer.
C1 [Park, Jeongwon; Kim, Won Gu; Zhao, Li; Enomoto, Keisuke; Willingham, Mark; Cheng, Sheue-Yann] NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bldg 37, Bethesda, MD 20892 USA.
[Kim, Won Gu] Univ Ulsan, Coll Med, Dept Internal Med, Div Endocrinol,Asan Med Ctr, Seoul 138736, South Korea.
RP Cheng, SY (reprint author), NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bldg 37, Bethesda, MD 20892 USA.
EM chengs@mail.nih.gov
OI Kim, Won Gu/0000-0002-8404-7759
FU Intramural Research Program at the Center for Cancer Research; National
Cancer Institute,; National Institutes of Health
FX The present research was supported by the Intramural Research Program at
the Center for Cancer Research, National Cancer Institute, National
Institutes of Health.
NR 55
TC 0
Z9 0
U1 3
U2 8
PU IMPACT JOURNALS LLC
PI ALBANY
PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA
SN 1949-2553
J9 ONCOTARGET
JI Oncotarget
PD JUN 7
PY 2016
VL 7
IS 23
BP 34832
EP 34844
DI 10.18632/oncotarget.8989
PG 13
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA DO4KS
UT WOS:000377752100096
PM 27145454
ER
PT J
AU Vassilev, A
Lee, CY
Vassilev, B
Zhu, WG
Ormanoglu, P
Martin, SE
DePamphilis, ML
AF Vassilev, Alex
Lee, Chrissie Y.
Vassilev, Boris
Zhu, Wenge
Ormanoglu, Pinar
Martin, Scott E.
DePamphilis, Melvin L.
TI Identification of genes that are essential to restrict genome
duplication to once per cell division
SO ONCOTARGET
LA English
DT Article
DE DNA re-replication; endoreplication; cell cycle regulation; aneuploidy;
polyploidy
ID DNA-DAMAGE RESPONSE; SPINDLE ASSEMBLY CHECKPOINT; EARLY
EMBRYONIC-DEVELOPMENT; SCALE RNAI SCREENS; CYCLE PROGRESSION;
CANCER-CELLS; CHROMOSOMAL INSTABILITY; TUMOR SUPPRESSION;
MAMMALIAN-CELLS; RE-REPLICATION
AB Nuclear genome duplication is normally restricted to once per cell division, but aberrant events that allow excess DNA replication (EDR) promote genomic instability and aneuploidy, both of which are characteristics of cancer development. Here we provide the first comprehensive identification of genes that are essential to restrict genome duplication to once per cell division. An siRNA library of 21,584 human genes was screened for those that prevent EDR in cancer cells with undetectable chromosomal instability. Candidates were validated by testing multiple siRNAs and chemical inhibitors on both TP53+ and TP53-cells to reveal the relevance of this ubiquitous tumor suppressor to preventing EDR, and in the presence of an apoptosis inhibitor to reveal the full extent of EDR. The results revealed 42 genes that prevented either DNA re-replication or unscheduled endoreplication. All of them participate in one or more of eight cell cycle events. Seventeen of them have not been identified previously in this capacity. Remarkably, 14 of the 42 genes have been shown to prevent aneuploidy in mice. Moreover, suppressing a gene that prevents EDR increased the ability of the chemotherapeutic drug Paclitaxel to induce EDR, suggesting new opportunities for synthetic lethalities in the treatment of human cancers.
C1 [Vassilev, Alex; Lee, Chrissie Y.; Vassilev, Boris; DePamphilis, Melvin L.] NICHHD, NIH, Bethesda, MD 20892 USA.
[Lee, Chrissie Y.] NantBioscience, Culver City, CA 90232 USA.
[Zhu, Wenge] George Washington Univ, Dept Biochem & Mol Biol, Washington, DC 20037 USA.
[Ormanoglu, Pinar; Martin, Scott E.] NIH, Natl Ctr Adv Translat Sci, Rockville, MD 20850 USA.
[Martin, Scott E.] Genentech Inc, San Francisco, CA 94080 USA.
RP DePamphilis, ML (reprint author), NICHHD, NIH, Bethesda, MD 20892 USA.
EM depamphm@mail.nih.gov
FU National Institutes of Health (NIH) Roadmap for Medical Research; NIH
Molecular Libraries Program; intramural research programs of the
National Human Genome Research Institute; National Institute of Child
Health and Human Development; NIH grants [CA177898, CA184717]
FX This work was supported by the National Institutes of Health (NIH)
Roadmap for Medical Research, the NIH Molecular Libraries Program, the
intramural research programs of the National Human Genome Research
Institute and the National Institute of Child Health and Human
Development, a Director's Challenge grant awarded to M.L.D, and NIH
grants CA177898 and CA184717 awarded to W.Z.
NR 84
TC 2
Z9 2
U1 1
U2 2
PU IMPACT JOURNALS LLC
PI ALBANY
PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA
SN 1949-2553
J9 ONCOTARGET
JI Oncotarget
PD JUN 7
PY 2016
VL 7
IS 23
BP 34956
EP 34976
DI 10.18632/oncotarget.9008
PG 21
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA DO4KS
UT WOS:000377752100105
PM 27144335
ER
PT J
AU Kang, HS
Takeda, Y
Jeon, K
Jetten, AM
AF Kang, Hong Soon
Takeda, Yukimasa
Jeon, Kilsoo
Jetten, Anton M.
TI The Spatiotemporal Pattern of Glis3 Expression Indicates a Regulatory
Function in Bipotent and Endocrine Progenitors during Early Pancreatic
Development and in Beta, PP and Ductal Cells
SO PLOS ONE
LA English
DT Article
ID POLYCYSTIC KIDNEY-DISEASE; NEONATAL DIABETES-MELLITUS; ZINC-FINGER
PROTEINS; PHYSIOLOGICAL FUNCTIONS; LINEAGE DETERMINANTS; ADULT PANCREAS;
NEUROGENIN 3; TRANSCRIPTION; GENE; LOCI
AB The transcription factor Glis-similar 3 (Glis3) has been implicated in the development of neonatal, type 1 and type 2 diabetes. In this study, we examined the spatiotemporal expression of Glis3 protein during embryonic and neonatal pancreas development as well as its function in PP cells. To obtain greater insights into the functions of Glis3 in pancreas development, we examined the spatiotemporal expression of Glis3 protein in a knockin mouse strain expressing a Glis3-EGFP fusion protein. Immunohistochemistry showed that Glis3-EGFP was not detectable during early pancreatic development (E11.5 and E12.5) and at E13.5 and 15.5 was not expressed in Ptf1a(+) cells in the tip domains indicating that Glis3 is not expressed in multipotent pancreatic progenitors. Glis3 was first detectable at E13.5 in the nucleus of bipotent progenitors in the trunk domains, where it co-localized with Sox9, Hnf6, and Pdx1. It remained expressed in preductal and Ngn3(+) endocrine progenitors and at later stages becomes restricted to the nucleus of pancreatic beta and PP cells as well as ductal cells. Glis3-deficiency greatly reduced, whereas exogenous Glis3, induced Ppy expression, as reported for insulin. Collectively, our study demonstrates that Glis3 protein exhibits a temporal and cell type-specific pattern of expression during embryonic and neonatal pancreas development that is consistent with a regulatory role for Glis3 in promoting endocrine progenitor generation, regulating insulin and Ppy expression in beta and PP cells, respectively, and duct morphogenesis.
C1 [Kang, Hong Soon; Takeda, Yukimasa; Jeon, Kilsoo; Jetten, Anton M.] NIEHS, Cell Biol Grp, Immun Inflammat & Dis Lab, Div Intramural Res,NIH, POB 12233, Res Triangle Pk, NC 27709 USA.
RP Jetten, AM (reprint author), NIEHS, Cell Biol Grp, Immun Inflammat & Dis Lab, Div Intramural Res,NIH, POB 12233, Res Triangle Pk, NC 27709 USA.
EM jetten@niehs.nih.gov
OI Jetten, Anton/0000-0003-0954-4445
FU National Institute of Environmental Health Sciences, National Institutes
of Health [Z01-ES-100485]; Intramural Research Program of the National
Institute of Environmental Health Sciences, the National Institutes of
Health [Z01-ES-100485]
FX Funded by National Institute of Environmental Health Sciences, National
Institutes of Health Z01-ES-100485.; This research was supported by the
Intramural Research Program of the National Institute of Environmental
Health Sciences, the National Institutes of Health [Z01-ES-100485]. The
authors thank Laura Miller DeGraff for her excellent assistance with
managing the mouse colonies.
NR 46
TC 4
Z9 4
U1 1
U2 4
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUN 7
PY 2016
VL 11
IS 6
AR e0157138
DI 10.1371/journal.pone.0157138
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DO1TC
UT WOS:000377561000067
PM 27270601
ER
PT J
AU Botos, I
Majdalani, N
Mayclin, SJ
McCarthy, JG
Lundquist, K
Wojtowicz, D
Barnard, TJ
Gumbart, JC
Buchanan, SK
AF Botos, Istvan
Majdalani, Nadim
Mayclin, Stephen J.
McCarthy, Jennifer Gehret
Lundquist, Karl
Wojtowicz, Damian
Barnard, Travis J.
Gumbart, James C.
Buchanan, Susan K.
TI Structural and Functional Characterization of the LPS Transporter LptDE
from Gram-Negative Pathogens
SO STRUCTURE
LA English
DT Article
ID TRANSENVELOPE PROTEIN COMPLEX; OUTER-MEMBRANE BIOGENESIS;
ESCHERICHIA-COLI; LIPOPOLYSACCHARIDE TRANSPORT; PSEUDOMONAS-AERUGINOSA;
BETA-BARREL; PEPTIDOMIMETIC ANTIBIOTICS; CRYSTAL-STRUCTURE; BAM COMPLEX;
EXPORT
AB Incorporation of lipopolysaccharide (LPS) into the outer membrane of Gram-negative bacteria is essential for viability, and is accomplished by a two-protein complex called LptDE. We solved crystal structures of the core LptDE complexes from Yersinia pestis, Klebsiella pneumoniae, Pseudomonas aeruginosa, and a full-length structure of the K. pneumoniae LptDE complex. Our structures adopt the same plug and 26-strand beta-barrel architecture found recently for the Shigella flexneri and Salmonella typhimurium LptDE structures, illustrating a conserved fold across the family. A comparison of the only two full-length structures, SfLptDE and our KpLptDE, reveals a 21 degrees rotation of the LptD N-terminal domain that may impart flexibility on the trans-envelope LptCAD scaffold. Utilizingmutagenesis coupled to an in vivo functional assay and molecular dynamics simulations, we demonstrate the critical role of Pro231 and Pro246 in the function of the LptD lateral gate that allows partitioning of LPS into the outer membrane.
C1 [Botos, Istvan; Mayclin, Stephen J.; McCarthy, Jennifer Gehret; Barnard, Travis J.; Buchanan, Susan K.] NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
[Majdalani, Nadim] NCI, Mol Biol Lab, NIH, Bldg 37, Bethesda, MD 20892 USA.
[Lundquist, Karl; Gumbart, James C.] Georgia Inst Technol, Sch Phys, Atlanta, GA 30332 USA.
[Wojtowicz, Damian] NIH, Natl Ctr Biotechnol Informat, Bldg 10, Bethesda, MD 20892 USA.
RP Buchanan, SK (reprint author), NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
EM skbuchan@helix.nih.gov
FU Intramural Research Program of the NIH, National Institute of Diabetes
and Digestive and Kidney Diseases; National Cancer Institute; National
Center for Biotechnology Information; National Science Foundation
[MCB-1452464]; NSF [OCI-1053575]; US Department of Energy, Office of
Science, Office of Basic Energy Sciences
FX This work was supported by the Intramural Research Program of the NIH,
National Institute of Diabetes and Digestive and Kidney Diseases
(S.J.M., J.G.M., I.B., T.J.B., and S.K.B.), National Cancer Institute
(N.M.), and National Center for Biotechnology Information (D.W.). J.C.G.
is supported by a National Science Foundation CAREER award
(MCB-1452464). Computational resources were provided through the Extreme
Science and Engineering Discovery Environment (XSEDE), which is
supported by NSF grant number OCI-1053575. We thank the staff at GM/CA
and SER-CAT beam lines at the Advanced Photon Source, Argonne National
Laboratory, for their assistance during data collection. Use of the
Advanced Photon Source was supported by the US Department of Energy,
Office of Science, Office of Basic Energy Sciences.
NR 61
TC 2
Z9 2
U1 8
U2 12
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0969-2126
EI 1878-4186
J9 STRUCTURE
JI Structure
PD JUN 7
PY 2016
VL 24
IS 6
BP 965
EP 976
DI 10.1016/j.str.2016.03.026
PG 12
WC Biochemistry & Molecular Biology; Biophysics; Cell Biology
SC Biochemistry & Molecular Biology; Biophysics; Cell Biology
GA DO4VE
UT WOS:000377782200017
PM 27161977
ER
PT J
AU Cartagena-Rivera, AX
Logue, JS
Waterman, CM
Chadwick, RS
AF Cartagena-Rivera, Alexander X.
Logue, Jeremy S.
Waterman, Clare M.
Chadwick, Richard S.
TI Actomyosin Cortical Mechanical Properties in Nonadherent Cells
Determined by Atomic Force Microscopy
SO BIOPHYSICAL JOURNAL
LA English
DT Article
ID LIVE CELLS; ACTIN NETWORKS; SURFACE; MYOSIN; MORPHOGENESIS; FIBROBLASTS;
PRESSURE; TENSION; CORTEX; MODEL
AB The organization of filamentous actin and myosin II molecular motor contractility is known to modify the mechanical properties of the cell cortical actomyosin cytoskeleton. Here we describe a novel method, to our knowledge, for using force spectroscopy approach curves with tipless cantilevers to determine the actomyosin cortical tension, elastic modulus, and intracellular pressure of nonadherent cells. We validated the method by measuring the surface tension of water in oil microdrops deposited on a glass surface. We extracted an average tension of T similar to 20.25 nN/mu m, which agrees with macroscopic experimental methods. We then measured cortical mechanical properties in nonadherent human foreskin fibroblasts and THP-1 human monocytes before and after pharmacological perturbations of actomyosin activity. Our results show that myosin II activity and actin polymerization increase cortex tension and intracellular pressure, whereas branched actin networks decreased them. Interestingly, myosin II activity stiffens the cortex and branched actin networks soften it, but actin polymerization has no effect on cortex stiffness. Our method is capable of detecting changes in cell mechanical properties in response to perturbations of the cytoskeleton, allowing characterization with physically relevant parameters. Altogether, this simple method should be of broad application for deciphering the molecular regulation of cell cortical mechanical properties.
C1 [Cartagena-Rivera, Alexander X.; Logue, Jeremy S.; Chadwick, Richard S.] Natl Inst Deafness & Other Commun Disorders, Lab Cellular Biol, Sect Auditory Mech, NIH, Bethesda, MD USA.
[Logue, Jeremy S.; Waterman, Clare M.] NHLBI, Cell Biol & Physiol Ctr, NIH, Bldg 10, Bethesda, MD 20892 USA.
RP Chadwick, RS (reprint author), Natl Inst Deafness & Other Commun Disorders, Lab Cellular Biol, Sect Auditory Mech, NIH, Bethesda, MD USA.
EM chadwick@helix.nih.gov
FU Intramural Programs of the US National Institute of Deafness and Other
Communication Disorders; National Heart, Lung, and Blood Institute
FX We are grateful for the support of this work by the Intramural Programs
of the US National Institute of Deafness and Other Communication
Disorders and National Heart, Lung, and Blood Institute.
NR 63
TC 3
Z9 3
U1 5
U2 5
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD JUN 7
PY 2016
VL 110
IS 11
BP 2528
EP 2539
DI 10.1016/j.bpj.2016.04.034
PG 12
WC Biophysics
SC Biophysics
GA DN7VO
UT WOS:000377288500027
PM 27276270
ER
PT J
AU Dabin, J
Mencarelli, A
McMillan, D
Romanyukha, A
Struelens, L
Lee, C
AF Dabin, Jeremie
Mencarelli, Alessandra
McMillan, Dayton
Romanyukha, Anna
Struelens, Lara
Lee, Choonsik
TI Validation of calculation algorithms for organ doses in CT by
measurements on a 5 year old paediatric phantom
SO PHYSICS IN MEDICINE AND BIOLOGY
LA English
DT Article
DE CT; organ dose; anthropomorphic phantom; Monte Carlo simulation
AB Many organ dose calculation tools for computed tomography (CT) scans rely on the assumptions: (1) organ doses estimated for one CT scanner can be converted into organ doses for another CT scanner using the ratio of the Computed Tomography Dose Index (CTDI) between two CT scanners; and (2) helical scans can be approximated as the summation of axial slices covering the same scan range. The current study aims to validate experimentally these two assumptions.
We performed organ dose measurements in a 5 year-old physical anthropomorphic phantom for five different CT scanners from four manufacturers. Absorbed doses to 22 organs were measured using thermoluminescent dosimeters for head-to-torso scans. We then compared the measured organ doses with the values calculated from the National Cancer Institute dosimetry system for CT (NCICT) computer program, developed at the National Cancer Institute.
Whereas the measured organ doses showed significant variability (coefficient of variation (CoV) up to 53% at 80 kV) across different scanner models, the CoV of organ doses normalised to CTDIvol substantially decreased (12% CoV on average at 80 kV). For most organs, the difference between measured and simulated organ doses was within +/- 20% except for the bone marrow, breasts and ovaries. The discrepancies were further explained by additional Monte Carlo calculations of organ doses using a voxel phantom developed from CT images of the physical phantom.
The results demonstrate that organ doses calculated for one CT scanner can be used to assess organ doses from other CT scanners with 20% uncertainty (k = 1), for the scan settings considered in the study.
C1 [Dabin, Jeremie; Mencarelli, Alessandra; Struelens, Lara] Belgian Nucl Res Ctr, Dept Radiat Protect Dosimetry & Calibrat, B-2400 Mol, Belgium.
[McMillan, Dayton; Romanyukha, Anna; Lee, Choonsik] NCI, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20850 USA.
RP Dabin, J (reprint author), Belgian Nucl Res Ctr, Dept Radiat Protect Dosimetry & Calibrat, B-2400 Mol, Belgium.
EM jdabin@sckcen.be
FU European Community's Seventh Framework Programme (FP7) [269912]
FX These measurements were performed within the framework of the EPI-CT
study, supported by the European Community's Seventh Framework Programme
(FP7/2007-2013) under grant agreement number 269912. The authors are
thankful to the medical staff for its help during the measurements.
NR 16
TC 0
Z9 0
U1 3
U2 6
PU IOP PUBLISHING LTD
PI BRISTOL
PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND
SN 0031-9155
EI 1361-6560
J9 PHYS MED BIOL
JI Phys. Med. Biol.
PD JUN 7
PY 2016
VL 61
IS 11
BP 4168
EP 4182
DI 10.1088/0031-9155/61/11/4168
PG 15
WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging
SC Engineering; Radiology, Nuclear Medicine & Medical Imaging
GA DN9VB
UT WOS:000377427700018
PM 27192093
ER
PT J
AU Reuben, A
Tillman, H
Fontana, RJ
Davern, T
McGuire, B
Stravitz, RT
Durkalski, V
Larson, AM
Liou, I
Fix, O
Schilsky, M
McCashland, T
Hay, JE
Murray, N
Shaikh, OS
Ganger, D
Zaman, A
Han, SB
Chung, RT
Smith, A
Brown, R
Crippin, J
Harrison, ME
Koch, D
Munoz, S
Reddy, KR
Rossaro, L
Satyanarayana, R
Hassanein, T
Hanje, AJ
Olson, J
Subramanian, R
Karvellas, C
Hameed, B
Sherker, AH
Robuck, P
Lee, WM
AF Reuben, Adrian
Tillman, Holly
Fontana, Robert J.
Davern, Timothy
McGuire, Brendan
Stravitz, R. Todd
Durkalski, Valerie
Larson, Anne M.
Liou, Iris
Fix, Oren
Schilsky, Michael
McCashland, Timothy
Hay, J. Eileen
Murray, Natalie
Shaikh, Obaid S.
Ganger, Daniel
Zaman, Atif
Han, Steven B.
Chung, Raymond T.
Smith, Alastair
Brown, Robert
Crippin, Jeffrey
Harrison, M. Edwyn
Koch, David
Munoz, Santiago
Reddy, K. Rajender
Rossaro, Lorenzo
Satyanarayana, Raj
Hassanein, Tarek
Hanje, A. James
Olson, Jody
Subramanian, Ram
Karvellas, Constantine
Hameed, Bilal
Sherker, Averell H.
Robuck, Patricia
Lee, William M.
TI Outcomes in Adults With Acute Liver Failure Between 1998 and 2013 An
Observational Cohort Study
SO ANNALS OF INTERNAL MEDICINE
LA English
DT Article
ID RETROSPECTIVE COHORT; INTENSIVE-CARE; CLINICAL-TRIAL; UNITED-STATES;
ENCEPHALOPATHY; COMPLICATIONS; MULTICENTER
AB Background: Acute liver failure (ALF) is a rare syndrome of severe, rapid-onset hepatic dysfunction-without prior advanced liver disease-that is associated with high morbidity and mortality. Intensive care and liver transplantation provide support and rescue, respectively.
Objective: To determine whether changes in causes, disease severity, treatment, or 21-day outcomes have occurred in recent years among adult patients with ALF referred to U.S. tertiary care centers.
Design: Prospective observational cohort study. (ClinicalTrials.gov: NCT00518440)
Setting: 31 liver disease and transplant centers in the United States.
Patients: Consecutively enrolled patients-without prior advanced liver disease-with ALF (n = 2070).
Measurements: Clinical features, treatment, and 21-day outcomes were compared over time annually for trends and were also stratified into two 8-year periods (1998 to 2005 and 2006 to 2013).
Results: Overall clinical characteristics, disease severity, and distribution of causes remained similar throughout the study period. The 21-day survival rates increased between the two 8-year periods (overall, 67.1% vs. 75.3%; transplant-free survival [TFS], 45.1% vs. 56.2%; posttransplantation survival, 88.3% vs. 96.3% [P < 0.010 for each]). Reductions in red blood cell infusions (44.3% vs. 27.6%), plasma infusions (65.2% vs. 47.1%), mechanical ventilation (65.7% vs. 56.1%), and vasopressors (34.9% vs. 27.8%) were observed, as well as increased use of N-acetylcysteine (48.9% vs. 69.3% overall; 15.8% vs. 49.4% [P < 0.001] in patients with ALF not due to acetaminophen toxicity). When examined longitudinally, overall survival and TFS increased throughout the 16-year period.
Limitations: The duration of enrollment, the number of patients enrolled, and possibly the approaches to care varied among participating sites. The results may not be generalizable beyond such specialized centers.
Conclusion: Although characteristics and severity of ALF changed little over 16 years, overall survival and TFS improved significantly. The effects of specific changes in intensive care practice on survival warrant further study.
C1 [Lee, William M.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA.
Baylor Univ, Med Ctr, Dallas, TX USA.
Med Univ S Carolina, Charleston, SC 29425 USA.
Univ Washington, Seattle, WA 98195 USA.
Washington Univ, St Louis, MO USA.
Univ Calif San Francisco, San Francisco, CA 94143 USA.
Calif Pacific Med Ctr, San Francisco, CA USA.
Univ Nebraska, Omaha, NE 68182 USA.
Mt Sinai Med Ctr, New York, NY 10029 USA.
Columbia Univ, Med Ctr, New York, NY USA.
Mayo Clin, Rochester, MN USA.
Univ Pittsburgh, Pittsburgh, PA USA.
Northwestern Univ, Chicago, IL 60611 USA.
Oregon Hlth & Sci Univ, Portland, OR USA.
Univ Calif Los Angeles, Los Angeles, CA USA.
Univ Michigan, Ann Arbor, MI 48109 USA.
Yale Univ, New Haven, CT USA.
Univ Alabama Birmingham, Birmingham, AL USA.
Massachusetts Gen Hosp, Boston, MA 02114 USA.
Duke Univ, Durham, NC USA.
Mayo Clin, Scottsdale, AZ USA.
Albert Einstein Med Ctr, Philadelphia, PA 19141 USA.
Univ Penn, Philadelphia, PA 19104 USA.
Virginia Commonwealth Univ, Richmond, VA USA.
Univ Calif Davis, Davis, CA 95616 USA.
Mayo Clin, Jacksonville, FL 32224 USA.
Univ Calif San Diego, San Diego, CA 92103 USA.
Ohio State Univ, Columbus, OH 43210 USA.
Univ Kansas, Med Ctr, Kansas City, KS 66103 USA.
Emory Univ, Atlanta, GA 30322 USA.
Univ Alberta, Edmonton, AB, Canada.
NIDDK, Bethesda, MD 20892 USA.
RP Lee, WM (reprint author), Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA.
EM william.lee@utsouthwestern.edu
OI Karvellas, Constantine/0000-0002-1555-1089
FU National Institute of Diabetes and Digestive and Kidney Diseases of the
National Institutes of Health [DK-U-01-58369]
FX By the National Institute of Diabetes and Digestive and Kidney Diseases
of the National Institutes of Health (DK-U-01-58369).
NR 19
TC 6
Z9 6
U1 1
U2 6
PU AMER COLL PHYSICIANS
PI PHILADELPHIA
PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA
SN 0003-4819
EI 1539-3704
J9 ANN INTERN MED
JI Ann. Intern. Med.
PD JUN 7
PY 2016
VL 164
IS 11
BP 724
EP +
DI 10.7326/M15-2211
PG 10
WC Medicine, General & Internal
SC General & Internal Medicine
GA DO1AI
UT WOS:000377510100004
PM 27043883
ER
PT J
AU Ulrich, CM
Grady, C
AF Ulrich, Connie M.
Grady, Christine
TI Nurses and Industry: Conflict or Collaboration?
SO ANNALS OF INTERNAL MEDICINE
LA English
DT Editorial Material
ID EDUCATION
C1 [Ulrich, Connie M.] Univ Penn, Sch Nursing, Philadelphia, PA 19104 USA.
[Ulrich, Connie M.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Grady, Christine] NIH, Ctr Clin, Bethesda, MD 20892 USA.
[Grady, Christine] NIH, Bldg 10,Room 1C118, Bethesda, MD 20892 USA.
RP Ulrich, CM (reprint author), Univ Penn, Sch Nursing, Philadelphia, PA 19104 USA.; Ulrich, CM (reprint author), Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA.
EM culrich@nursing.upenn.edu
NR 8
TC 0
Z9 0
U1 2
U2 2
PU AMER COLL PHYSICIANS
PI PHILADELPHIA
PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA
SN 0003-4819
EI 1539-3704
J9 ANN INTERN MED
JI Ann. Intern. Med.
PD JUN 7
PY 2016
VL 164
IS 11
BP 773
EP +
DI 10.7326/M16-0707
PG 3
WC Medicine, General & Internal
SC General & Internal Medicine
GA DO1AI
UT WOS:000377510100010
PM 27042939
ER
PT J
AU Santhanakrishnan, R
Wang, N
Larson, MG
Magnani, JW
McManus, DD
Lubitz, SA
Ellinor, PT
Cheng, S
Vasan, RS
Lee, DS
Wang, TJ
Levy, D
Benjamin, EJ
Ho, JE
AF Santhanakrishnan, Rajalakshmi
Wang, Na
Larson, Martin G.
Magnani, Jared W.
McManus, David D.
Lubitz, Steven A.
Ellinor, Patrick T.
Cheng, Susan
Vasan, Ramachandran S.
Lee, Douglas S.
Wang, Thomas J.
Levy, Daniel
Benjamin, Emelia J.
Ho, Jennifer E.
TI Response to Letter Regarding Article, "Atrial Fibrillation Begets Heart
Failure and Vice Versa: Temporal Associations and Differences in
Preserved Versus Reduced Ejection Fraction"
SO CIRCULATION
LA English
DT Letter
ID COMMUNITY
C1 [Santhanakrishnan, Rajalakshmi; Magnani, Jared W.] Boston Univ, Sch Med, Dept Med, Cardiovasc Med Sect, Boston, MA 02118 USA.
[Wang, Na] Boston Univ, Data Coordinating Ctr, Boston, MA 02215 USA.
[Larson, Martin G.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA.
[McManus, David D.] Univ Massachusetts, Sch Med, Dept Med, Div Cardiol, Boston, MA 02125 USA.
[Lubitz, Steven A.; Ellinor, Patrick T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA 02115 USA.
[Cheng, Susan; Levy, Daniel] NHLBI, Framingham, MA USA.
[Cheng, Susan; Levy, Daniel] Boston Univ, Framingham Heart Study, Framingham, MA USA.
[Vasan, Ramachandran S.] Boston Univ, Sch Med, Sect Prevent Med & Epidemiol, Boston, MA 02118 USA.
[Lee, Douglas S.] Univ Toronto, Inst Clin Evaluat Sci, Toronto, ON M5S 1A1, Canada.
[Lee, Douglas S.] Univ Toronto, Toronto Gen Hosp, Toronto, ON M5S 1A1, Canada.
[Wang, Thomas J.] Vanderbilt Univ, Dept Med, Div Cardiovasc Med, 221 Kirkland Hall, Nashville, TN 37235 USA.
[Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02215 USA.
[Ho, Jennifer E.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.
RP Santhanakrishnan, R (reprint author), Boston Univ, Sch Med, Dept Med, Cardiovasc Med Sect, Boston, MA 02118 USA.
OI Ramachandran, Vasan/0000-0001-7357-5970
FU NHLBI NIH HHS [K23 HL116780]
NR 4
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0009-7322
EI 1524-4539
J9 CIRCULATION
JI Circulation
PD JUN 7
PY 2016
VL 133
IS 23
BP E692
EP E693
DI 10.1161/CIRCULATIONAHA.116.022835
PG 2
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA DN9ZT
UT WOS:000377439900003
PM 27267541
ER
PT J
AU Katki, HA
Kovalchik, SA
Berg, CD
Cheung, LC
Chaturvedi, AK
AF Katki, Hormuzd A.
Kovalchik, Stephanie A.
Berg, Christine D.
Cheung, Li C.
Chaturvedi, Anil K.
TI Development and Validation of Risk Models to Select Ever-Smokers for CT
Lung Cancer Screening
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Article
ID SERVICES TASK-FORCE; COMPUTED-TOMOGRAPHY; TRIAL; PREDICTION; PROSTATE;
GUIDELINES; MANAGEMENT; MORTALITY; BENEFITS; OUTCOMES
AB IMPORTANCE The US Preventive Services Task Force (USPSTF) recommends computed tomography (CT) lung cancer screening for ever-smokers aged 55 to 80 years who have smoked at least 30 pack-years with no more than 15 years since quitting. However, selecting ever-smokers for screening using individualized lung cancer risk calculations may be more effective and efficient than current USPSTF recommendations.
OBJECTIVE Comparison of modeled outcomes from risk-based CT lung-screening strategies vs USPSTF recommendations.
DESIGN, SETTING, AND PARTICIPANTS Empirical risk models for lung cancer incidence and death in the absence of CT screening using data on ever-smokers from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO; 1993-2009) control group. Covariates included age; education; sex; race; smoking intensity, duration, and quit-years; body mass index; family history of lung cancer; and self-reported emphysema. Model validation in the chest radiography groups of the PLCO and the National Lung Screening Trial (NLST; 2002-2009), with additional validation of the death model in the National Health Interview Survey (NHIS; 1997-2001), a representative sample of the United States. Models were applied to US ever-smokers aged 50 to 80 years (NHIS 2010-2012) to estimate outcomes of risk-based selection for CT lung screening, assuming screening for all ever-smokers, yield the percent changes in lung cancer detection and death observed in the NLST.
EXPOSURES Annual CT lung screening for 3 years beginning at age 50 years.
MAIN OUTCOMES AND MEASURES For model validity: calibration (number of model-predicted cases divided by number of observed cases [estimated/observed]) and discrimination (area under curve [AUC]). For modeled screening outcomes: estimated number of screen-avertable lung cancer deaths and estimated screening effectiveness (number needed to screen [NNS] to prevent 1 lung cancer death).
RESULTS Lung cancer incidence and death risk models were well calibrated in PLCO and NLST. The lung cancer death model calibrated and discriminated well for US ever-smokers aged 50 to 80 years (NHIS 1997-2001: estimated/observed = 0.94 [95% CI, 0.84-1.05]; AUC, 0.78 [95% CI, 0.76-0.80]). Under USPSTF recommendations, the models estimated 9.0 million US ever-smokers would qualify for lung cancer screening and 46 488 (95% CI, 43 924-49 053) lung cancer deaths were estimated as screen-avertable over 5 years (estimated NNS, 194 [95% CI, 187-201]). In contrast, risk-based selection screening of the same number of ever-smokers (9.0 million) at highest 5-year lung cancer risk (>= 1.9%) was estimated to avert 20% more deaths (55 717 [95% CI, 53 033-58 400]) and was estimated to reduce the estimated NNS by 17%(NNS, 162 [95% CI, 157-166]).
CONCLUSIONS AND RELEVANCE Among a cohort of US ever-smokers aged 50 to 80 years, application of a risk-based model for CT screening for lung cancer compared with a model based on USPSTF recommendations was estimated to be associated with a greater number of lung cancer deaths prevented over 5 years, along with a lower NNS to prevent 1 lung cancer death.
C1 [Katki, Hormuzd A.; Berg, Christine D.; Chaturvedi, Anil K.] NCI, Div Canc Epidemiol & Genet, NIH, US Dept HHS, 9609 Med Ctr Dr,Room 7E606, Bethesda, MD 20892 USA.
[Kovalchik, Stephanie A.] Victoria Univ, Inst Sport Exercise & Act Living, Melbourne, Vic 8001, Australia.
[Berg, Christine D.] Johns Hopkins Med, Dept Radiat Oncol & Mol Radiat Sci, Baltimore, MD USA.
[Cheung, Li C.] Informat Management Serv Inc, Calverton, MD USA.
RP Katki, HA (reprint author), NCI, Div Canc Epidemiol & Genet, 9609 Med Ctr Dr,Room 7E606, Bethesda, MD 20892 USA.; Chaturvedi, AK (reprint author), NCI, Div Canc Epidemiol & Genet, 9609 Med Ctr Dr,Room 6E238, Bethesda, MD 20892 USA.
EM katkih@mail.nih.gov; chaturva@mail.nih.gov
OI Cheung, Li/0000-0003-1625-4331
FU Intramural Research Program of the US National Institutes of Health
(NIH)/National Cancer Institute
FX This study was supported by the Intramural Research Program of the US
National Institutes of Health (NIH)/National Cancer Institute.
NR 40
TC 8
Z9 9
U1 2
U2 5
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 0098-7484
EI 1538-3598
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD JUN 7
PY 2016
VL 315
IS 21
BP 2300
EP 2311
DI 10.1001/jama.2016.6255
PG 12
WC Medicine, General & Internal
SC General & Internal Medicine
GA DN6KO
UT WOS:000377183100019
PM 27179989
ER
PT J
AU Gilroy, DW
Edin, ML
De Maeyer, RPH
Bystrom, J
Newson, J
Lih, FB
Stables, M
Zeldin, DC
Bishop-Bailey, D
AF Gilroy, Derek W.
Edin, Matthew L.
De Maeyer, Roel P. H.
Bystrom, Jonas
Newson, Justine
Lih, Fred B.
Stables, Melanie
Zeldin, Darryl C.
Bishop-Bailey, David
TI CYP450-derived oxylipins mediate inflammatory resolution
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE oxylipins; resolution; monocyte; phagocytosis; epoxygenase
ID SOLUBLE EPOXIDE HYDROLASE; ISCHEMIA-REPERFUSION INJURY;
ARACHIDONIC-ACID; IN-VIVO; EPOXYEICOSATRIENOIC ACIDS; ATHEROSCLEROTIC
PLAQUES; ENDOTHELIAL EXPRESSION; VASCULAR INFLAMMATION; BLOOD-PRESSURE;
FATTY-ACIDS
AB Resolution of inflammation has emerged as an active process in immunobiology, with cells of the mononuclear phagocyte system being critical in mediating efferocytosis and wound debridement and bridging the gap between innate and adaptive immunity. Here we investigated the roles of cytochrome P450 (CYP)-derived epoxy-oxylipins in a well-characterized model of sterile resolving peritonitis in the mouse. Epoxy-oxylipins were produced in a biphasic manner during the peaks of acute (4 h) and resolution phases (24-48 h) of the response. The epoxygenase inhibitor SKF525A (epoxI) given at 24 h selectively inhibited arachidonic acid-and linoleic acid-derived CYP450-epoxy-oxlipins and resulted in a dramatic influx in monocytes. The epoxI-recruited monocytes were strongly GR1(+), Ly6c(hi), CCR2(hi), CCL2(hi), and CX3CR1(lo). In addition, expression of F4/80 and the recruitment of T cells, B cells, and dendritic cells were suppressed. sEH (Ephx2)(-/-) mice, which have elevated epoxy-oxylipins, demonstrated opposing effects to epoxitreated mice: reduced Ly6c(hi) monocytes and elevated F4/80(hi) macrophages and B, T, and dendritic cells. Ly6c(hi) and Ly6c(lo) monocytes, resident macrophages, and recruited dendritic cells all showed a dramatic change in their resolution signature following in vivo epoxI treatment. Markers of macrophage differentiation CD11b, MerTK, and CD103 were reduced, and monocyte-derived macrophages and resident macrophages ex vivo showed greatly impaired phagocytosis of zymosan and efferocytosis of apoptotic thymocytes following epoxI treatment. These findings demonstrate that epoxy-oxylipins have a critical role in monocyte lineage recruitment and activity to promote inflammatory resolution and represent a previously unidentified internal regulatory system governing the establishment of adaptive immunity.
C1 [Gilroy, Derek W.; De Maeyer, Roel P. H.; Newson, Justine; Stables, Melanie] UCL, Div Med, Ctr Clin Pharmacol & Therapeut, London WC1E 6JJ, England.
[Edin, Matthew L.; Lih, Fred B.; Zeldin, Darryl C.] NIEHS, Div Intramural Res, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.
[Bystrom, Jonas] Queen Mary Univ London, William Harvey Res Inst, London EC1M 6BQ, England.
[Bishop-Bailey, David] Univ London Royal Vet Coll, Comparat Biomed Sci, 32 Belgrave Sq, London NW1 0TU, England.
RP Gilroy, DW (reprint author), UCL, Div Med, Ctr Clin Pharmacol & Therapeut, London WC1E 6JJ, England.; Bishop-Bailey, D (reprint author), Univ London Royal Vet Coll, Comparat Biomed Sci, 32 Belgrave Sq, London NW1 0TU, England.
EM d.gilroy@ucl.ac.uk; dbishopbailey@rvc.ac.uk
FU British Heart Foundation [PG/08/070/25464, PG/11/39/28890]; Intramural
Research Program of the National Institutes of Health, National
Institute of Environmental Health Sciences [Z01 ES025034]; Wellcome
Trust
FX We thank the Mass Spectrometry Core at the NIEHS for their technical
assistance and Dr. Mark Paul Clark, Imperial College London, for his
help with data analysis. This work was funded by grants from the British
Heart Foundation (PG/08/070/25464, PG/11/39/28890) and the Intramural
Research Program of the National Institutes of Health, National
Institute of Environmental Health Sciences, Grant Z01 ES025034 (to
D.C.Z.). D.W.G. holds a Wellcome Trust Senior Fellowship.
NR 59
TC 1
Z9 1
U1 2
U2 6
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD JUN 7
PY 2016
VL 113
IS 23
BP E3240
EP E3249
DI 10.1073/pnas.1521453113
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DN6BF
UT WOS:000377155400010
PM 27226306
ER
PT J
AU Wang, TY
Lee, SY
Chen, SL
Chang, YH
Wang, LJ
Chen, PS
Chen, SH
Chu, CH
Huang, SY
Tzeng, NS
Li, CL
Chung, YL
Hsieh, TH
Lee, IH
Chen, KC
Yang, YK
Hong, JS
Lu, RB
AF Wang, Tzu-Yun
Lee, Sheng-Yu
Chen, Shiou-Lan
Chang, Yun-Hsuan
Wang, Liang-Jen
Chen, Po See
Chen, Shih-Heng
Chu, Chun-Hsien
Huang, San-Yuan
Tzeng, Nian-Sheng
Li, Chia-Ling
Chung, Yi-Lun
Hsieh, Tsai-Hsin
Lee, I. Hui
Chen, Kao Chin
Yang, Yen Kuang
Hong, Jau-Shyong
Lu, Ru-Band
TI Comparing clinical responses and the biomarkers of BDNF and cytokines
between subthreshold bipolar disorder and bipolar II disorder
SO SCIENTIFIC REPORTS
LA English
DT Article
ID MAJOR DEPRESSIVE DISORDER; COMORBIDITY SURVEY REPLICATION; INDUCED
MICROGLIAL ACTIVATION; NEUROTROPHIC FACTOR; INFLAMMATORY MARKERS;
OXIDATIVE STRESS; PRIVATE-PRACTICE; RATING-SCALE; IFN-GAMMA; BRAIN
AB Patients with subthreshold hypomania (SBP; subthreshold bipolar disorder) were indistinguishable from those with bipolar disorder (BP)-II on clinical bipolar validators, but their analyses lacked biological and pharmacological treatment data. Because inflammation and neuroprogression underlies BP, we hypothesized that cytokines and brain-derived neurotrophic factor (BDNF) are biomarkers for BP. We enrolled 41 drug-naive patients with SBP and 48 with BP-II undergoing 12 weeks of pharmacological treatment (valproic acid, fluoxetine, risperidone, lorazepam). The Hamilton Depression Rating Scale (HDRS) and Young Mania Rating Scale (YMRS) were used to evaluate clinical responses at baseline and at weeks 0, 1, 2, 4, 8, and 12. Inflammatory cytokines (tumour necrosis factor [TNF]-alpha, transforming growth factor [TGF]-beta 1, interleukin [IL]-6, IL-8 and IL-1 beta) and BDNF levels were also measured. Mixed models repeated measurement was used to examine the therapeutic effect and changes in BDNF and cytokine levels between the groups. HDRS and YMRS scores significantly (P < 0.001) declined in both groups, the SBP group had significantly lower levels of BDNF (P = 0.005) and TGF-beta 1 (P = 0.02). Patients with SBP and BP-II respond similarly to treatment, but SBP patients may have different neuroinflammation marker expression.
C1 [Wang, Tzu-Yun; Lee, Sheng-Yu; Chen, Shiou-Lan; Chang, Yun-Hsuan; Chen, Po See; Li, Chia-Ling; Chung, Yi-Lun; Hsieh, Tsai-Hsin; Lee, I. Hui; Chen, Kao Chin; Yang, Yen Kuang; Lu, Ru-Band] Natl Cheng Kung Univ, Coll Med, Natl Cheng Kung Univ Hosp, Dept Psychiat, Tainan 70101, Taiwan.
[Lee, Sheng-Yu] Kaohsiung Vet Gen Hosp, Dept Psychiat, Kaohsiung, Taiwan.
[Chen, Shiou-Lan] KMU, Lipid Sci & Aging Res Ctr, Coll Med, Grad Inst Med, Kaohsiung, Taiwan.
[Chang, Yun-Hsuan; Lu, Ru-Band] Natl Cheng Kung Univ, Coll Med, Inst Allied Hlth Sci, Tainan 70101, Taiwan.
[Chang, Yun-Hsuan] Asia Univ, Dept Psychol, Taichung, Taiwan.
[Wang, Liang-Jen] Kaohsiung Chang Gung Mem Hosp, Dept Child & Adolescent Psychiat, Kaohsiung, Taiwan.
[Wang, Liang-Jen] Chang Gung Univ, Coll Med, Kaohsiung, Taiwan.
[Chen, Po See; Lee, I. Hui; Chen, Kao Chin; Yang, Yen Kuang; Lu, Ru-Band] Natl Cheng Kung Univ, Addict Res Ctr, Tainan 701, Taiwan.
[Chen, Shih-Heng; Hong, Jau-Shyong] NIEHS, Neurobiol Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.
[Chu, Chun-Hsien] Natl Cheng Kung Univ, Coll Med, Inst Mol Med, Tainan 70101, Taiwan.
[Huang, San-Yuan; Tzeng, Nian-Sheng] Triserv Gen Hosp, Natl Def Med Ctr, Dept Psychiat, Taipei, Taiwan.
[Tzeng, Nian-Sheng] Natl Def Med Ctr, Student Counseling Ctr, Taipei, Taiwan.
[Chung, Yi-Lun] Natl Cheng Kung Univ, Inst Basic Med Sci, Tainan 701, Taiwan.
[Yang, Yen Kuang; Lu, Ru-Band] Natl Cheng Kung Univ, Coll Med, Inst Behav Med, Tainan 70101, Taiwan.
[Yang, Yen Kuang] Natl Cheng Kung Univ Hosp, Dou Liou Branch, Dept Psychiat, Yunlin, Taiwan.
[Lu, Ru-Band] Natl Hlth Res Inst, Ctr Neuropsychiat Res, Miaoli, Taiwan.
RP Lu, RB (reprint author), Natl Cheng Kung Univ, Coll Med, Natl Cheng Kung Univ Hosp, Dept Psychiat, Tainan 70101, Taiwan.; Lu, RB (reprint author), Natl Cheng Kung Univ, Coll Med, Inst Allied Hlth Sci, Tainan 70101, Taiwan.; Lu, RB (reprint author), Natl Cheng Kung Univ, Addict Res Ctr, Tainan 701, Taiwan.; Lu, RB (reprint author), Natl Cheng Kung Univ, Coll Med, Inst Behav Med, Tainan 70101, Taiwan.; Lu, RB (reprint author), Natl Hlth Res Inst, Ctr Neuropsychiat Res, Miaoli, Taiwan.
EM rblu@mail.ncku.edu.tw
FU Taiwan National Science Council [NSC98-2314-B-006-022-MY3,
NSC102-2622-B-006-002-CC2, NSC100-2314-B-075B-010-MY3]; Taiwan
Department of Health [DOH 95-TD-M-113-055]; Taiwan National Health
Research Institute [NHRI-EX-97-9738NI]; National Cheng Kung University
Project for Promoting Academic Excellence and Developing World Class
Research Centers; National Cheng Kung University Hospital
[NCKUH-10505007]
FX This work was supported in part by grant NSC98-2314-B-006-022-MY3,
NSC102-2622-B-006-002-CC2(to RBL) and grant NSC100-2314-B-075B-010-MY3
(to SYL) from the Taiwan National Science Council, grant DOH
95-TD-M-113-055 (to RBL) from the Taiwan Department of Health, grant
NHRI-EX-97-9738NI (to RBL) from the Taiwan National Health Research
Institute, the National Cheng Kung University Project for Promoting
Academic Excellence and Developing World Class Research Centers, and
grant NCKUH-10505007(to TYW) from National Cheng Kung University
Hospital.
NR 59
TC 1
Z9 1
U1 3
U2 13
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2045-2322
J9 SCI REP-UK
JI Sci Rep
PD JUN 7
PY 2016
VL 6
AR 27431
DI 10.1038/srep27431
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DN6IK
UT WOS:000377177200001
PM 27270858
ER
PT J
AU Spong, CY
AF Spong, Catherine Y.
TI Understanding Zika virus pathogenesis: an interview with Catherine Spong
SO BMC MEDICINE
LA English
DT Editorial Material
DE Zika; Infants; Pregnancy; Neurology; Microcephaly; Miscarriage;
Stillbirth; Infectious disease; Cohort; Fetal anomaly
AB A recent outbreak of Zika virus has been linked to fetal abnormalities in pregnant women who have been infected. The scientific community is working toward understanding Zika virus pathogenesis to better manage affected women and children. In an interview with Dr. Catherine Spong, we discuss the aims and challenges of a forthcoming longitudinal study of a cohort of pregnant women in areas of current active Zika virus transmission.
C1 [Spong, Catherine Y.] NICHHD, Eunice Kennedy Shriver, NIH, Bethesda, MD 20892 USA.
RP Spong, CY (reprint author), NICHHD, Eunice Kennedy Shriver, NIH, Bethesda, MD 20892 USA.
EM spongc@mail.nih.gov
NR 9
TC 0
Z9 0
U1 30
U2 43
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1741-7015
J9 BMC MED
JI BMC Med.
PD JUN 6
PY 2016
VL 14
AR 84
DI 10.1186/s12916-016-0628-0
PG 4
WC Medicine, General & Internal
SC General & Internal Medicine
GA DO2DA
UT WOS:000377588700001
PM 27268016
ER
PT J
AU Ohzeki, J
Shono, N
Otake, K
Martins, NMC
Kugou, K
Kimura, H
Nagase, T
Larionov, V
Earnshaw, WC
Masumoto, H
AF Ohzeki, Jun-ichirou
Shono, Nobuaki
Otake, Koichiro
Martins, Nuno M. C.
Kugou, Kazuto
Kimura, Hiroshi
Nagase, Takahiro
Larionov, Vladimir
Earnshaw, William C.
Masumoto, Hiroshi
TI KAT7/HBO1/MYST2 Regulates CENP-A Chromatin Assembly by Antagonizing
Suv39h1-Mediated Centromere Inactivation
SO DEVELOPMENTAL CELL
LA English
DT Article
ID HBO1 HISTONE ACETYLASE; FISSION YEAST; ARTIFICIAL CHROMOSOMES;
EPIGENETIC REGULATION; ALPHOID DNA; B INTERACTS; HETEROCHROMATIN;
KINETOCHORE; NUCLEOSOMES; PROTEINS
AB Centromere chromatin containing histone H3 variant CENP-A is required for accurate chromosome segregation as a foundation for kinetochore assembly. Human centromere chromatin assembles on a part of the long a-satellite (alphoid) DNA array, where it is flanked by pericentric heterochromatin. Heterochromatin spreads into adjacent chromatin and represses gene expression, and it can antagonize centromere function or CENP-A assembly. Here, we demonstrate an interaction between CENP-A assembly factor M18BP1 and acetyltransferase KAT7/HBO1/MYST2. Knocking out KAT7 in HeLa cells reduced centromeric CENP-A assembly. Mitotic chromosome misalignment and micronuclei formation increased in the knockout cells and were enhanced when the histone H3-K9 trimethylase Suv39h1 was overproduced. Tethering KAT7 to an ectopic alphoid DNA integration site removed heterochromatic H3K9me3 modification and was sufficient to stimulate new CENP-A or histone H3.3 assembly. Thus, KAT7-containing acetyltransferases associating with the Mis18 complex provides competence for histone turnover/exchange activity on alphoid DNA and prevents Suv39h1-mediated heterochromatin invasion into centromeres.
C1 [Ohzeki, Jun-ichirou; Shono, Nobuaki; Otake, Koichiro; Kugou, Kazuto; Masumoto, Hiroshi] Kazusa DNA Res Inst, Dept Frontier Res, Lab Cell Engn, 2-6-7 Kazusa Kamatari, Kisarazu 2920818, Japan.
[Martins, Nuno M. C.; Earnshaw, William C.] Univ Edinburgh, Wellcome Trust Ctr Cell Biol, Edinburgh EH9 3BF, Midlothian, Scotland.
[Kimura, Hiroshi] Tokyo Inst Technol, Grad Sch Biosci & Biotechnol, Dept Biol Sci, Yokohama, Kanagawa 2268501, Japan.
[Nagase, Takahiro] Kazusa DNA Res Inst, Publ Relat Team, Kisarazu 2920818, Japan.
[Larionov, Vladimir] NCI, Genome Struct & Funct Grp, Dev Therapeut Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA.
RP Masumoto, H (reprint author), Kazusa DNA Res Inst, Dept Frontier Res, Lab Cell Engn, 2-6-7 Kazusa Kamatari, Kisarazu 2920818, Japan.
EM masumoto@kazusa.or.jp
RI Shono, Nobuaki/C-4130-2017;
OI Shono, Nobuaki/0000-0002-9060-1074; Martins, Nuno/0000-0003-3953-9313
FU MEXT KAKENHI grants [23247030, 23114008, 16H04747, 16H01414]; Kazusa DNA
Research Institute Foundation; Wellcome Trust [073915]; Japan Society
for the Promotion of Science; Ministry of Education, Culture, Sports,
Science and Technology of Japan; NIH, National Cancer Institute; Center
for Cancer Research
FX We would like to thank Hiroko Shinohara, Tomoe Hayashi, and Kazuko
Yamada for their technical assistance, Koei Okazaki for discussion, and
Naohito Nozaki for producing the antibodies. This work was supported by
MEXT KAKENHI grants 23247030, 23114008, 16H04747, and 16H01414, as well
as the Kazusa DNA Research Institute Foundation (H.M.). Work in the
W.C.E. laboratory is funded by the Wellcome Trust, of which W.C.E. is a
Principal Research Fellow (grant no. 073915). Additional experiments
were supported by grants-in-aid from the Japan Society for the Promotion
of Science and the Ministry of Education, Culture, Sports, Science and
Technology of Japan (to H.K.) and the intramural research program of the
NIH, National Cancer Institute, and Center for Cancer Research (to
V.L.).
NR 58
TC 6
Z9 6
U1 0
U2 2
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1534-5807
EI 1878-1551
J9 DEV CELL
JI Dev. Cell
PD JUN 6
PY 2016
VL 37
IS 5
BP 413
EP 427
DI 10.1016/j.devcel.2016.05.006
PG 15
WC Cell Biology; Developmental Biology
SC Cell Biology; Developmental Biology
GA DN9OC
UT WOS:000377408100008
PM 27270040
ER
PT J
AU Sawyer, LA
Dundr, M
AF Sawyer, Lain A.
Dundr, Miroslav
TI Nuclear bodies: Built to boost
SO JOURNAL OF CELL BIOLOGY
LA English
DT Editorial Material
ID CAJAL BODIES; ORGANIZATION; PARTICLES; GENOME
AB The classic archetypal function of nuclear bodies is to accelerate specific reactions within their crowded space. In this issue, Tatomer et al. (2016. J. Cell Biol. http://dx.doi.org/10.1083/jcb.201504043) provide the first direct evidence that the histone locus body acts to concentrate key factors required for the proper processing of histone pre-mRNAs.
C1 [Sawyer, Lain A.; Dundr, Miroslav] Rosalind Franklin Univ Med & Sci, Chicago Med Sch, Dept Cell Biol, N Chicago, IL 60064 USA.
[Sawyer, Lain A.] NCI, Lab Receptor Biol & Gene Express, NIH, Bethesda, MD 20892 USA.
RP Dundr, M (reprint author), Rosalind Franklin Univ Med & Sci, Chicago Med Sch, Dept Cell Biol, N Chicago, IL 60064 USA.
EM mirek.dundr@rosalindfranklin.edu
NR 20
TC 1
Z9 1
U1 2
U2 7
PU ROCKEFELLER UNIV PRESS
PI NEW YORK
PA 950 THIRD AVE, 2ND FLR, NEW YORK, NY 10022 USA
SN 0021-9525
EI 1540-8140
J9 J CELL BIOL
JI J. Cell Biol.
PD JUN 6
PY 2016
VL 213
IS 5
BP 509
EP 511
DI 10.1083/jcb.201605049
PG 3
WC Cell Biology
SC Cell Biology
GA DO1RA
UT WOS:000377555500005
ER
PT J
AU Timilsina, U
Ghimire, D
Timalsina, B
Nitz, TJ
Wild, CT
Freed, EO
Gaur, R
AF Timilsina, Uddhav
Ghimire, Dibya
Timalsina, Bivek
Nitz, Theodore J.
Wild, Carl T.
Freed, Eric O.
Gaur, Ritu
TI Identification of potent maturation inhibitors against HIV-1 clade C
SO SCIENTIFIC REPORTS
LA English
DT Article
ID IMMUNODEFICIENCY-VIRUS TYPE-1; BETULINIC ACID-DERIVATIVES; GAG SPACER
PEPTIDE-1; CA-SP1 CLEAVAGE SITE; BEVIRIMAT; RESISTANCE; POLYMORPHISMS;
ENVELOPE; PA-457; STEP
AB Antiretroviral therapy has led to a profound improvement in the clinical care of HIV-infected patients. However, drug tolerability and the evolution of drug resistance have limited treatment options for many patients. Maturation inhibitors are a new class of antiretroviral agents for treatment of HIV-1. They act by interfering with the maturation of the virus by blocking the last step in Gag processing: the cleavage of the capsid-spacer peptide 1 (CA-SP1) intermediate to mature CA by the viral protease (PR). The first-in-class maturation inhibitor bevirimat (BVM) failed against a subset of HIV-1 isolates in clinical trials due to polymorphisms present in the CA-SP1 region of the Gag protein. Sequence analysis indicated that these polymorphisms are more common in non-clade B strains of HIV-1 such as HIV-1 clade C. Indeed, BVM was found to be ineffective against HIV-1 clade C molecular clones tested in this study. A number of BVM analogs were synthesized by chemical modifications at the C-28 position to improve its activity. The new BVM analogs displayed potent activity against HIV-1 clade B and C and also reduced infectivity of the virus. This study identifies novel and broadly active BVM analogs that may ultimately demonstrate efficacy in the clinic.
C1 [Timilsina, Uddhav; Ghimire, Dibya; Timalsina, Bivek; Gaur, Ritu] South Asian Univ, Fac Life Sci & Biotechnol, New Delhi 110021, India.
[Nitz, Theodore J.; Wild, Carl T.] DFH Pharma, Gaithersburg, MD 20886 USA.
[Freed, Eric O.] NCI, Virus Cell Interact Sect, HIV Dynam & Replicat Program, Ctr Canc Res, Rockville, MD 21702 USA.
RP Gaur, R (reprint author), South Asian Univ, Fac Life Sci & Biotechnol, New Delhi 110021, India.
EM rgaur@sau.ac.in
OI Timalsina, Bivek/0000-0003-0734-0780
FU South Asian University Intramural Research Fund; NIH Intramural to India
(I-I) [BT/MB/Indo-US/I-I/02/ 2013]
FX This research was supported by South Asian University Intramural
Research Fund and the NIH Intramural to India (I-I) [grant
BT/MB/Indo-US/I-I/02/ 2013] to Ritu Gaur. The funders had no role in
study design, data collection, interpretation and the decision to submit
the work for publication.
NR 30
TC 2
Z9 2
U1 1
U2 3
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2045-2322
J9 SCI REP-UK
JI Sci Rep
PD JUN 6
PY 2016
VL 6
AR 27403
DI 10.1038/srep27403
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DN5TA
UT WOS:000377132300001
PM 27264714
ER
PT J
AU Kellock, J
Hopping, G
Caughey, B
Daggett, V
AF Kellock, Jackson
Hopping, Gene
Caughey, Byron
Daggett, Valerie
TI Peptides Composed of Alternating L- and D-Amino Acids Inhibit
Amyloidogenesis in Three Distinct Amyloid Systems Independent of
Sequence
SO JOURNAL OF MOLECULAR BIOLOGY
LA English
DT Article
DE beta amyloid; amyloid; toxic oligomer; inhibitor; alpha-sheet
ID A-BETA OLIGOMERS; ALZHEIMERS-DISEASE; PRION PROTEIN; CONFORMATIONAL
PROPENSITIES; AGGREGATION PATHWAYS; COMMON MECHANISM; SHEET STRUCTURE;
ALPHA-SHEET; IN-VITRO; TRANSTHYRETIN
AB There is now substantial evidence that soluble oligomers are primary toxic agents in amyloid diseases. The development of an antibody recognizing the toxic soluble oligomeric forms of different and unrelated amyloid species suggests a common conformational intermediate during amyloidogenesis. We previously observed a common occurrence of a novel secondary structure element, which we call alpha-sheet, in molecular dynamics (MD) simulations of various amyloidogenic proteins, and we hypothesized that the toxic conformer is composed of alpha-sheet structure. As such, alpha-sheet may represent a conformational signature of the misfolded intermediates of amyloidogenesis and a potential unique binding target for peptide inhibitors. Recently, we reported the design and characterization of a novel hairpin peptide (alpha 1 or AP90) that adopts stable alpha-sheet structure and inhibits the aggregation of the (beta-Amyloid Peptide A beta 42 and transthyretin. AP90 is a 23-residue hairpin peptide featuring alternating D- and L-amino acids with favorable conformational propensities for alpha-sheet formation, and a designed turn. For this study, we reverse engineered AP90 to identify which of its design features is most responsible for conferring alpha-sheet stability and inhibitory activity. We present experimental characterization (CD and FTIR) of seven peptides designed to accomplish this. In addition, we measured their ability to inhibit aggregation in three unrelated amyloid species: A beta 42, transthyretin, and human islet amylin polypeptide. We found that a hairpin peptide featuring alternating L- and D-amino acids, independent of sequence, is sufficient for conferring alpha-sheet structure and inhibition of aggregation. Additionally, we show a correlation between alpha-sheet structural stability and inhibitory activity. (C) 2016 Elsevier Ltd. All rights reserved.
C1 [Kellock, Jackson; Hopping, Gene; Daggett, Valerie] Univ Washington, Dept Bioengn, Seattle, WA 98105 USA.
[Caughey, Byron] NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA.
RP Daggett, V (reprint author), Univ Washington, Dept Bioengn, Seattle, WA 98105 USA.
EM daggett@uw.edu
FU W.H. Coulter Foundation Translational Research Partnership Program;
National Science Foundation [CBET-0966977]; National Institute of Health
[GM 95808]; Coins for Alzheimer's Research Trust; Intramural Research
Program of the NIAID, NIH
FX We thank Dr. James Bryers, Dr. David Baker, Dr. Cecilia Giachelli, Dr.
Buddy Ratner, and Dr. Pat Stayton for the generous use of equipment. We
thank Dr. Tom Schmidlin for his advice on figure design. This study was
funded by the W.H. Coulter Foundation Translational Research Partnership
Program (to V.D.), grants from the National Science Foundation
(CBET-0966977 to V.D.), the National Institute of Health (GM 95808 to
V.D.), the Coins for Alzheimer's Research Trust (to V.D.), and the
Intramural Research Program of the NIAID, NIH (to B.C.).
NR 52
TC 3
Z9 3
U1 11
U2 28
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0022-2836
EI 1089-8638
J9 J MOL BIOL
JI J. Mol. Biol.
PD JUN 5
PY 2016
VL 428
IS 11
BP 2317
EP 2328
DI 10.1016/j.jmb.2016.03.013
PG 12
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA DO4DY
UT WOS:000377733200006
PM 27012425
ER
PT J
AU Botesteanu, DA
Lee, JM
Levy, D
AF Botesteanu, Dana-Adriana
Lee, Jung-Min
Levy, Doron
TI Modeling the Dynamics of High-Grade Serous Ovarian Cancer Progression
for Transvaginal Ultrasound-Based Screening and Early Detection
SO PLOS ONE
LA English
DT Article
ID BRCA1/2 MUTATION CARRIERS; FALLOPIAN-TUBE; CLINICAL-IMPLICATIONS;
FOLLOW-UP; CARCINOMAS; EVOLUTION; SURVIVAL; HISTORY; BREAST; WOMEN
AB High-grade serous ovarian cancer (HGSOC) represents the majority of ovarian cancers and accounts for the largest proportion of deaths from the disease. A timely detection of low volume HGSOC should be the goal of any screening studies. However, numerous transvaginal ultrasound (TVU) detection-based population studies aimed at detecting low-volume disease have not yielded reduced mortality rates. A quantitative invalidation of TVU as an effective HGSOC screening strategy is a necessary next step. Herein, we propose a mathematical model for a quantitative explanation on the reported failure of TVU-based screening to improve HGSOC low-volume detectability and overall survival. We develop a novel in silico mathematical assessment of the efficacy of a unimodal TVU monitoring regimen as a strategy aimed at detecting low-volume HGSOC in cancer-positive cases, defined as cases for which the inception of the first malignant cell has already occurred. Our findings show that the median window of opportunity interval length for TVU monitoring and HGSOC detection is approximately 1.76 years. This does not translate into reduced mortality levels or improved detection accuracy in an in silico cohort across multiple TVU monitoring frequencies or detection sensitivities. We demonstrate that even a semiannual, unimodal TVU monitoring protocol is expected to miss detectable HGSOC. Lastly, we find that circa 50% of the simulated HGSOC growth curves never reach the baseline detectability threshold, and that on average, 5-7 infrequent, rate-limiting stochastic changes in the growth parameters are associated with reaching HGSOC detectability and mortality thresholds respectively. Focusing on a malignancy poorly studied in the mathematical oncology community, our model captures the dynamic, temporal evolution of HGSOC progression. Our mathematical model is consistent with recent case reports and prospective TVU screening population studies, and provides support to the empirical recommendation against frequent HGSOC screening.
C1 [Botesteanu, Dana-Adriana; Levy, Doron] Univ Maryland, Dept Math, College Pk, MD 20742 USA.
[Botesteanu, Dana-Adriana; Levy, Doron] Univ Maryland, Ctr Sci Computat & Math Modeling CSCAMM, College Pk, MD 20742 USA.
[Botesteanu, Dana-Adriana; Lee, Jung-Min] NCI, Womens Malignancies Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Levy, D (reprint author), Univ Maryland, Dept Math, College Pk, MD 20742 USA.; Levy, D (reprint author), Univ Maryland, Ctr Sci Computat & Math Modeling CSCAMM, College Pk, MD 20742 USA.
EM dlevy@math.umd.edu
FU Intramural Research Program of the National Institutes of Health; Center
for Cancer Research, National Cancer Institute as part of a seed grant
from the UMD-NCI Partnership for Cancer Technology; John Simon
Guggenheim Memorial Foundation
FX The work was supported by the Intramural Research Program of the
National Institutes of Health, Center for Cancer Research, National
Cancer Institute as part of a seed grant from the UMD-NCI Partnership
for Cancer Technology. The work of DL was supported in part by the John
Simon Guggenheim Memorial Foundation. The funders had no role in study
design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 58
TC 2
Z9 2
U1 1
U2 2
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUN 3
PY 2016
VL 11
IS 6
AR e0156661
DI 10.1371/journal.pone.0156661
PG 19
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DN8ZV
UT WOS:000377369700096
PM 27257824
ER
PT J
AU Huang, BN
Gomez-Rodriguez, J
Preite, S
Garrett, LJ
Harper, UL
Schwartzberg, PL
AF Huang, Bonnie
Gomez-Rodriguez, Julio
Preite, Silvia
Garrett, Lisa J.
Harper, Ursula L.
Schwartzberg, Pamela L.
TI CRISPR-Mediated Triple Knockout of SLAMF1, SLAMF5 and SLAMF6 Supports
Positive Signaling Roles in NKT Cell Development
SO PLOS ONE
LA English
DT Article
ID LINKED LYMPHOPROLIFERATIVE-DISEASE; CONTROLS T-CELL; HUMORAL IMMUNITY;
NEGATIVE REGULATION; FAMILY RECEPTORS; GENE-PRODUCT; ADAPTER SAP;
B-CELLS; MICE; DIFFERENTIATION
AB The SLAM family receptors contribute to diverse aspects of lymphocyte biology and signal via the small adaptor molecule SAP. Mutations affecting SAP lead to X-linked lymphoproliferative syndrome Type 1, a severe immunodysregulation characterized by fulminant mononucleosis, dysgammaglobulinemia, and lymphoproliferation/lymphomas. Patients and mice having mutations affecting SAP also lack germinal centers due to a defect in T:B cell interactions and are devoid of invariant NKT (iNKT) cells. However, which and how SLAM family members contribute to these phenotypes remains uncertain. Three SLAM family members: SLAMF1, SLAMF5 and SLAMF6, are highly expressed on T follicular helper cells and germinal center B cells. SLAMF1 and SLAMF6 are also implicated in iNKT development. Although individual receptor knockout mice have limited iNKT and germinal center phenotypes compared to SAP knockout mice, the generation of multi-receptor knockout mice has been challenging, due to the genomic linkage of the genes encoding SLAM family members. Here, we used Cas9/CRISPR-based mutagenesis to generate mutations simultaneously in Slamf1, Slamf5 and Slamf6. Genetic disruption of all three receptors in triple-knockout mice (TKO) did not grossly affect conventional T or B cell development and led to mild defects in germinal center formation post-immunization. However, the TKO worsened defects in iNKT cells development seen in SLAMF6 single gene-targeted mice, supporting data on positive signaling and potential redundancy between these receptors.
C1 [Huang, Bonnie; Gomez-Rodriguez, Julio; Preite, Silvia; Schwartzberg, Pamela L.] NHGRI, Genet Dis Res Branch, Bethesda, MD 20892 USA.
[Garrett, Lisa J.] NHGRI, Embryon Stem Cell & Transgen Mouse Core, Bethesda, MD 20892 USA.
[Harper, Ursula L.] NHGRI, Genom Core, Bethesda, MD 20892 USA.
RP Schwartzberg, PL (reprint author), NHGRI, Genet Dis Res Branch, Bethesda, MD 20892 USA.
EM pams@mail.nih.gov
FU National Human Genome Research Institute [HG000123, HG200349]
FX This work was supported by intramural funding from the National Human
Genome Research Institute (HG000123 and HG200349).
NR 52
TC 1
Z9 1
U1 0
U2 0
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUN 3
PY 2016
VL 11
IS 6
AR e0156072
DI 10.1371/journal.pone.0156072
PG 19
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DN8ZV
UT WOS:000377369700033
PM 27258160
ER
PT J
AU Deshmukh, L
Schwieters, CD
Grishaev, A
Clore, GM
AF Deshmukh, Lalit
Schwieters, Charles D.
Grishaev, Alexander
Clore, G. Marius
TI Quantitative Characterization of Configurational Space Sampled by HIV-1
Nucleocapsid Using Solution NMR, X-ray Scattering and Protein
Engineering
SO CHEMPHYSCHEM
LA English
DT Article
DE HIV-1; nuclear magnetic resonance; nucleocapsid; protein engineering;
X-ray scattering
ID IMMUNODEFICIENCY-VIRUS TYPE-1; MOLECULAR-STRUCTURE DETERMINATION;
LIQUID-CRYSTALLINE PHASE; GAG POLYPROTEIN; STRUCTURAL-CHARACTERIZATION;
REVERSE TRANSCRIPTION; XPLOR-NIH; DYNAMICS; RNA; SPECTROSCOPY
AB Nucleic-acid-related events in the HIV-1 replication cycle are mediated by nucleocapsid, a small protein comprising two zinc knuckles connected by a short flexible linker and flanked by disordered termini. Combining experimental NMR residual dipolar couplings, solution X-ray scattering and protein engineering with ensemble simulated annealing, we obtain a quantitative description of the configurational space sampled by the two zinc knuckles, the linker and disordered termini in the absence of nucleic acids. We first compute the conformational ensemble (with an optimal size of three members) of an engineered nucleocapsid construct lacking the N- and C-termini that satisfies the experimental restraints, and then validate this ensemble, as well as characterize the disordered termini, using the experimental data from the full-length nucleocapsid construct. The experimental and computational strategy is generally applicable to multidomain proteins. Differential flexibility within the linker results in asymmetric motion of the zinc knuckles which may explain their functionally distinct roles despite high sequence identity. One of the configurations (populated at a level of. 40%) closely resembles that observed in various ligand-bound forms, providing evidence for conformational selection and a mechanistic link between protein dynamics and function.
C1 [Deshmukh, Lalit; Clore, G. Marius] NIDDK, Chem Phys Lab, Bldg 2, Bethesda, MD 20892 USA.
[Schwieters, Charles D.] Ctr Informat & Technol, Imaging Sci Lab, Bethesda, MD 20892 USA.
[Grishaev, Alexander] Univ Maryland, Inst Biosci & Biotechnol Res, Rockville, MD 20850 USA.
RP Clore, GM (reprint author), NIDDK, Chem Phys Lab, Bldg 2, Bethesda, MD 20892 USA.
EM mariusc@mail.nih.gov
FU DOE [W-31-109-ENG-38, PUP-77]; NIH, NIDDK; CIT; Intramural AIDS Targeted
Antiviral Program of the Office of the Director of the NIH
FX We thank Drs. Fang (NCI), Zuo (APS) and Seifert (APS) for assistance
with SAXS data collection; Drs. Baber, Cai, Garrett, Ghirlando and
Tugarinov for discussions. We acknowledge use of the Advanced Photon
Source (DOE contract #W-31-109-ENG-38 and PUP-77 agreement between NCI,
NIH and Argonne National Laboratory). This work was supported by the
Intramural Program of the NIH, NIDDK (to G.M.C.) and CIT (to C.D.S.),
and the Intramural AIDS Targeted Antiviral Program of the Office of the
Director of the NIH (to G.M.C.).
NR 34
TC 1
Z9 1
U1 1
U2 1
PU WILEY-V C H VERLAG GMBH
PI WEINHEIM
PA POSTFACH 101161, 69451 WEINHEIM, GERMANY
SN 1439-4235
EI 1439-7641
J9 CHEMPHYSCHEM
JI ChemPhysChem
PD JUN 3
PY 2016
VL 17
IS 11
BP 1548
EP 1552
DI 10.1002/cphc.201600212
PG 5
WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical
SC Chemistry; Physics
GA DT0MM
UT WOS:000381177700001
PM 26946052
ER
PT J
AU Taguchi, Y
Allende, ML
Mizukami, H
Cook, EK
Gavrilova, O
Tuymetova, G
Clarke, BA
Chen, WP
Olivera, A
Proia, RL
AF Taguchi, Yoshimitsu
Allende, Maria L.
Mizukami, Hiroki
Cook, Emily K.
Gavrilova, Oksana
Tuymetova, Galina
Clarke, Benjamin A.
Chen, Weiping
Olivera, Ana
Proia, Richard L.
TI Sphingosine-1-phosphate Phosphatase 2 Regulates Pancreatic Islet
beta-Cell Endoplasmic Reticulum Stress and Proliferation
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID UNFOLDED PROTEIN RESPONSE; TYPE-2 DIABETIC-PATIENTS; INSULIN-RESISTANCE;
PHOSPHOHYDROLASE; SPHINGOLIPIDS; SPHINGOSINE; MASS; IDENTIFICATION;
HOMEOSTASIS; METABOLISM
AB Sphingosine-1-phosphate (S1P) is a sphingolipid metabolite that regulates basic cell functions through metabolic and signaling pathways. Intracellular metabolism of S1P is controlled, in part, by two homologous S1P phosphatases (SPPases), 1 and 2, which are encoded by the Sgpp1 and Sgpp2 genes, respectively. SPPase activity is needed for efficient recycling of sphingosine into the sphingolipid synthesis pathway. SPPase 1 is important for skin homeostasis, but little is known about the functional role of SPPase 2. To identify the functions of SPPase 2 in vivo, we studied mice with the Sgpp2 gene deleted. In contrast to Sgpp1(-/)-mice, Sgpp2(-/)-mice had normal skin and were viable into adulthood. Unexpectedly, WT mice expressed Sgpp2 mRNA at high levels in pancreatic islets when compared with other tissues. Sgpp2(-/)-mice had normal pancreatic islet size; however, they exhibited defective adaptive beta-cell proliferation that was demonstrated after treatment with either a high-fat diet or the beta-cell-specific toxin, streptozotocin. Importantly, beta-cells from untreated Sgpp2(-/)-mice showed significantly increased expression of proteins characteristic of the endoplasmic reticulum stress response compared with beta-cells from WT mice, indicating a basal islet defect. Our results show that Sgpp2 deletion causes beta-cell endoplasmic reticulum stress, which is a known cause of beta-cell dysfunction, and reveal a juncture in the sphingolipid recycling pathway that could impact the development of diabetes.
C1 [Taguchi, Yoshimitsu; Allende, Maria L.; Cook, Emily K.; Tuymetova, Galina; Clarke, Benjamin A.; Proia, Richard L.] NIDDK, Genet Dev & Dis Branch, Bldg 10,Rm 9D-06,10 Ctr Dr MSC 1821, Bethesda, MD 20892 USA.
[Gavrilova, Oksana] NIDDK, Mouse Metab Core Lab, Bethesda, MD 20892 USA.
[Chen, Weiping] NIDDK, Genom Core, Bethesda, MD 20892 USA.
[Olivera, Ana] NIAID, Lab Allerg Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Mizukami, Hiroki] Hirosaki Univ, Grad Sch Med, Dept Pathol & Mol Med, Hirosaki, Aomori 0368562, Japan.
RP Proia, RL (reprint author), NIDDK, Genet Dev & Dis Branch, Bldg 10,Rm 9D-06,10 Ctr Dr MSC 1821, Bethesda, MD 20892 USA.
EM proia@nih.gov
FU Intramural Research Program of NIDDK, National Institutes of Health;
Intramural Research Program of NIAID, National Institutes of Health;
Lipidomics Shared Resource, Hollings Cancer Center, Medical University
of South Carolina [P30 CA138313]; Lipidomics Core in the SC Lipidomics
and Pathobiology COBRE [P20 RR017677]
FX This research was supported by the Intramural Research Programs of NIDDK
and NIAID, National Institutes of Health; the Lipidomics Shared
Resource, Hollings Cancer Center, Medical University of South Carolina (
Grant P30 CA138313); and the Lipidomics Core in the SC Lipidomics and
Pathobiology COBRE ( Grant P20 RR017677). The authors declare that they
have no conflicts of interest with the contents of this article. The
content is solely the responsibility of the authors and does not
necessarily represent the official views of the National Institutes of
Health.
NR 35
TC 1
Z9 1
U1 1
U2 2
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
EI 1083-351X
J9 J BIOL CHEM
JI J. Biol. Chem.
PD JUN 3
PY 2016
VL 291
IS 23
BP 12029
EP 12038
DI 10.1074/jbc.M116.728170
PG 10
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA DO9GJ
UT WOS:000378092800007
PM 27059959
ER
PT J
AU Gottlieb, SL
Deal, CD
Giersing, B
Rees, H
Bolan, G
Johnston, C
Timms, P
Gray-Owen, SD
Jerse, AE
Cameron, CE
Moorthy, VS
Kiarie, J
Broutet, N
AF Gottlieb, Sami L.
Deal, Carolyn D.
Giersing, Birgitte
Rees, Helen
Bolan, Gail
Johnston, Christine
Timms, Peter
Gray-Owen, Scott D.
Jerse, Ann E.
Cameron, Caroline E.
Moorthy, Vasee S.
Kiarie, James
Broutet, Nathalie
TI The global roadmap for advancing development of vaccines against
sexually transmitted infections: Update and next steps
SO VACCINE
LA English
DT Article
DE Sexually transmitted infections; Vaccines; STI vaccine development;
Roadmap
ID HERPES-SIMPLEX-VIRUS; PELVIC-INFLAMMATORY-DISEASE; TREPONEMA-PALLIDUM
STRAINS; GENITAL-TRACT INFECTION; NEISSERIA-GONORRHOEAE;
CHLAMYDIA-TRACHOMATIS; CHEMICAL MUTAGENESIS; SYSTEMATIC ANALYSIS;
COST-EFFECTIVENESS; HIV ACQUISITION
AB In 2014, the World Health Organization, the US National Institutes of Health, and global technical partners published a comprehensive roadmap for development of new vaccines against sexually transmitted infections (STIs). Since its publication, progress has been made in several roadmap activities: obtaining better epidemiologic data to establish the public health rationale for STI vaccines, modeling the theoretical impact of future vaccines, advancing basic science research, defining preferred product characteristics for first-generation vaccines, and encouraging investment in STI vaccine development. This article reviews these overarching roadmap activities, provides updates on research and development of individual vaccines against herpes simplex virus, Chlamydia trachomatis, Neisseria gonorrhoeae, and Treponema pallidum, and discusses important next steps to advance the global roadmap for STI vaccine development. (C) 2016 World Health Organization; licensee Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.orgilicensesiby/3.0/).
C1 [Gottlieb, Sami L.; Giersing, Birgitte; Moorthy, Vasee S.; Kiarie, James; Broutet, Nathalie] WHO, CH-1211 Geneva 27, Switzerland.
[Deal, Carolyn D.] NIAID, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Rees, Helen] Univ Witwatersrand, Wits Reprod Hlth & HIV Inst, Johannesburg, South Africa.
[Bolan, Gail] Ctr Dis Control & Prevent, Atlanta, GA USA.
[Johnston, Christine] Univ Washington, Seattle, WA 98195 USA.
[Timms, Peter] Univ Sunshine Coast, Sunshine Coast, Qld, Australia.
[Timms, Peter] Queensland Univ Technol, Inst Hlth & Biomed Innovat, Brisbane, Qld 4001, Australia.
[Gray-Owen, Scott D.] Univ Toronto, Toronto, ON, Canada.
[Jerse, Ann E.] Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA.
[Cameron, Caroline E.] Univ Victoria, Victoria, BC, Canada.
RP Gottlieb, SL (reprint author), WHO, Dept Reprod Hlth & Res, Ave Appia 20, CH-1211 Geneva 27, Switzerland.
EM gottliebs@who.int
FU Agenus; Genocea; Vical; Gilead; AiCuris; Sanofi
FX Drs. Gottlieb, Deal, Giersing, Rees, Bolan, Timms, Gray-Owen, Jerse,
Cameron, Moorthy, Kiarie, and Broutet report no potential conflicts of
interest. Dr. Johnston has conducted research at the University of
Washington sponsored by the following companies as a principal or
co-investigator: Agenus, Genocea, Vical, Gilead, AiCuris, and Sanofi.
NR 75
TC 6
Z9 6
U1 6
U2 8
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0264-410X
EI 1873-2518
J9 VACCINE
JI Vaccine
PD JUN 3
PY 2016
VL 34
IS 26
SI SI
BP 2939
EP 2947
DI 10.1016/j.vaccine.2016.03.111
PG 9
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA DP3AQ
UT WOS:000378365200016
PM 27105564
ER
PT J
AU de Maturana, EL
Picornell, A
Masson-Lecomte, A
Kogevinas, M
Marquez, M
Carrato, A
Tardon, A
Lloreta, J
Garcia-Closas, M
Silverman, D
Rothman, N
Chanock, S
Real, FX
Goddard, ME
Malats, N
AF Lopez de Maturana, E.
Picornell, A.
Masson-Lecomte, A.
Kogevinas, M.
Marquez, M.
Carrato, A.
Tardon, A.
Lloreta, J.
Garcia-Closas, M.
Silverman, D.
Rothman, N.
Chanock, S.
Real, F. X.
Goddard, M. E.
Malats, N.
CA SBC EPICURO Study Investigators
TI Prediction of non-muscle invasive bladder cancer outcomes assessed by
innovative multimarker prognostic models
SO BMC CANCER
LA English
DT Article
DE Multimarker models; Bayesian statistical learning method; Bayesian
regression; Bayesian LASSO; AUC-ROC; Determination coefficient;
heritability; Bladder cancer outcome; Prognosis; Recurrence;
Progression; Genome-wide common SNP; Illumina Infinium HumanHap 1 M
array; Predictive ability
ID BAYESIAN LASSO; EAU GUIDELINES; DAIRY-CATTLE; RISK; SURVIVAL;
PROGRESSION; RECURRENCE; UPDATE
AB Background: We adapted Bayesian statistical learning strategies to the prognosis field to investigate if genome-wide common SNP improve the prediction ability of clinico-pathological prognosticators and applied it to non-muscle invasive bladder cancer (NMIBC) patients.
Methods: Adapted Bayesian sequential threshold models in combination with LASSO were applied to consider the time-to-event and the censoring nature of data. We studied 822 NMIBC patients followed-up > 10 years. The study outcomes were time-to-first-recurrence and time-to-progression. The predictive ability of the models including up to 171,304 SNP and/or 6 clinico-pathological prognosticators was evaluated using AUC-ROC and determination coefficient.
Results: Clinico-pathological prognosticators explained a larger proportion of the time-to-first-recurrence (3.1 %) and time-to-progression (5.4 %) phenotypic variances than SNPs (1 and 0.01 %, respectively). Adding SNPs to the clinico-pathological-parameters model slightly improved the prediction of time-to-first-recurrence (up to 4 %). The prediction of time-to-progression using both clinico-pathological prognosticators and SNP did not improve. Heritability (h(2)) of both outcomes was < 1 % in NMIBC.
Conclusions: We adapted a Bayesian statistical learning method to deal with a large number of parameters in prognostic studies. Common SNPs showed a limited role in predicting NMIBC outcomes yielding a very low heritability for both outcomes. We report for the first time a heritability estimate for a disease outcome. Our method can be extended to other disease models.
C1 [Lopez de Maturana, E.; Picornell, A.; Masson-Lecomte, A.; Marquez, M.; Malats, N.] Spanish Natl Canc Res Ctr CNIO, Genet & Mol Epidemiol Grp, C Melchor Fernandez,Almagro 3, Madrid 28029, Spain.
[Kogevinas, M.] Ctr Res Environm Epidemiol CREAL, Parc Salut Mar, Barcelona, Spain.
[Carrato, A.] Hosp Univ Ramon & Cajal, Serv Oncol, Madrid, Spain.
[Carrato, A.] Hosp Univ Elche, Serv Oncol, Elche, Spain.
[Tardon, A.] Univ Oviedo, Dept Prevent Med, Oviedo, Spain.
[Lloreta, J.] Hosp Mar IMAS, Parc Salut Mar, Barcelona, Spain.
[Lloreta, J.] Hosp Mar IMAS, Dept Pathol, Barcelona, Spain.
[Garcia-Closas, M.] Inst Canc Res, Div Genet & Epidemiol, London SW3 6JB, England.
[Silverman, D.; Rothman, N.; Chanock, S.] NCI, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Real, F. X.] Spanish Natl Canc Res Ctr CNIO, Epithelial Carcinogenesis Grp, Madrid, Spain.
[Real, F. X.] Univ Pompeu Fabra, Dept Ciencies Expt Salut, Barcelona, Spain.
[Goddard, M. E.] Univ Melbourne, Dept Environm & Primary Ind, Biosci Res Div, Agribio, Melbourne, Vic, Australia.
[Goddard, M. E.] Univ Melbourne, Dept Food & Agr Syst, Melbourne, Vic, Australia.
[Tardon, A.] CIBERESP, Madrid, Spain.
RP Malats, N (reprint author), Spanish Natl Canc Res Ctr CNIO, Genet & Mol Epidemiol Grp, C Melchor Fernandez,Almagro 3, Madrid 28029, Spain.
EM nmalats@cnio.es
RI Kogevinas, Manolis/C-3918-2017; Real, Francisco X/H-5275-2015;
OI Real, Francisco X/0000-0001-9501-498X; Malats, Nuria/0000-0003-2538-3784
FU Red Tematica de Investigacion Cooperativa en Cancer [RD12/0036/0050];
Fondo de Investigaciones Sanitarias (FIS); Instituto de Salud Carlos III
[PI00-0745, PI05-1436, PI06-1614]; Asociacion Espanola Contra el Cancer
(AECC), Spain; Intramural Research Program of the Division of Cancer
Epidemiology and Genetics, National Cancer Institute, USA [NCI
NO2-CP-11015]; EU-7FP-HEALTH-TransBioBC [60193]; Sara Borrell
fellowship; Instituto de Salud Carlos III, Spain; European Urological
Scholarship Program for Research (EUSP Scholarship) [S-01-2013];
[EU-FP7-HEALTH-F2-2008-201663-UROMOL]
FX The work was partially supported by Red Tematica de Investigacion
Cooperativa en Cancer (#RD12/0036/0050), Fondo de Investigaciones
Sanitarias (FIS), Instituto de Salud Carlos III, (Grant numbers
#PI00-0745, #PI05-1436, and #PI06-1614), and Asociacion Espanola Contra
el Cancer (AECC), Spain; the Intramural Research Program of the Division
of Cancer Epidemiology and Genetics, National Cancer Institute, USA
(Contract NCI NO2-CP-11015); and EU-FP7-HEALTH-F2-2008-201663-UROMOL and
EU-7FP-HEALTH-TransBioBC #601933. ELM was funded by a Sara Borrell
fellowship, Instituto de Salud Carlos III, Spain; and AML by a
fellowship of the European Urological Scholarship Program for Research
(EUSP Scholarship S-01-2013).
NR 30
TC 0
Z9 0
U1 3
U2 5
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2407
J9 BMC CANCER
JI BMC Cancer
PD JUN 3
PY 2016
VL 16
AR 351
DI 10.1186/s12885-016-2361-7
PG 9
WC Oncology
SC Oncology
GA DN3LY
UT WOS:000376964900001
ER
PT J
AU Robb, ML
Eller, LA
Kibuuka, H
Rono, K
Maganga, L
Nitayaphan, S
Kroon, E
Sawe, FK
Sinei, S
Sriplienchan, S
Jagodzinski, LL
Malia, J
Manak, M
de Souza, MS
Tovanabutra, S
Sanders-Buell, E
Rolland, M
Dorsey-Spitz, J
Eller, MA
Milazzo, M
Li, Q
Lewandowski, A
Wu, H
Swann, E
O'Connell, RJ
Peel, S
Dawson, P
Kim, JH
Michael, NL
AF Robb, Merlin L.
Eller, Leigh A.
Kibuuka, Hannah
Rono, Kathleen
Maganga, Lucas
Nitayaphan, Sorachai
Kroon, Eugene
Sawe, Fred K.
Sinei, Samuel
Sriplienchan, Somchai
Jagodzinski, Linda L.
Malia, Jennifer
Manak, Mark
de Souza, Mark S.
Tovanabutra, Sodsai
Sanders-Buell, Eric
Rolland, Morgane
Dorsey-Spitz, Julie
Eller, Michael A.
Milazzo, Mark
Li, Qun
Lewandowski, Andrew
Wu, Hao
Swann, Edith
O'Connell, Robert J.
Peel, Sheila
Dawson, Peter
Kim, Jerome H.
Michael, Nelson L.
CA RV 217 Study Team
TI Prospective Study of Acute HIV-1 Infection in Adults in East Africa and
Thailand
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID VIRUS TYPE-1 INFECTION; T-CELL-ACTIVATION; VIRAL LOAD; SET-POINT;
ANTIRETROVIRAL THERAPY; RNA LEVELS; 1ST YEAR; TRANSMISSION; DYNAMICS;
PROGRESSION
AB BACKGROUND
Acute human immunodeficiency virus type 1 (HIV-1) infection is a major contributor to transmission of HIV-1. An understanding of acute HIV-1 infection may be important in the development of treatment strategies to eradicate HIV-1 or achieve a functional cure.
METHODS
We performed twice-weekly qualitative plasma HIV-1 RNA nucleic acid testing in 2276 volunteers who were at high risk for HIV-1 infection. For participants in whom acute HIV-1 infection was detected, clinical observations, quantitative measurements of plasma HIV-1 RNA levels (to assess viremia) and HIV antibodies, and results of immuno-phenotyping of lymphocytes were obtained twice weekly.
RESULTS
Fifty of 112 volunteers with acute HIV-1 infection had two or more blood samples collected before HIV-1 antibodies were detected. The median peak viremia (6.7 log 10 copies per milliliter) occurred 13 days after the first sample showed reactivity on nucleic acid testing. Reactivity on an enzyme immunoassay occurred at a median of 14 days. The nadir of viremia (4.3 log 10 copies per milliliter) occurred at a median of 31 days and was nearly equivalent to the viral-load set point, the steady-state viremia that persists durably after resolution of acute viremia (median plasma HIV-1 RNA level, 4.4 log 10 copies per milliliter). The peak viremia and downslope were correlated with the viralload set point. Clinical manifestations of acute HIV-1 infection were most common just before and at the time of peak viremia. A median of one symptom of acute HIV-1 infection was recorded at a median of two study visits, and a median of one sign of acute HIV-1 infection was recorded at a median of three visits.
CONCLUSIONS
The viral-load set point occurred at a median of 31 days after the first detection of plasma viremia and correlated with peak viremia. Few symptoms and signs were observed during acute HIV-1 infection, and they were most common before peak viremia. (Funded by the Department of Defense and the National Institute of Allergy and Infectious Diseases.)
C1 [Robb, Merlin L.; Eller, Leigh A.; Jagodzinski, Linda L.; Malia, Jennifer; Manak, Mark; Tovanabutra, Sodsai; Sanders-Buell, Eric; Rolland, Morgane; Dorsey-Spitz, Julie; Eller, Michael A.; Milazzo, Mark; Li, Qun; Peel, Sheila; Kim, Jerome H.; Michael, Nelson L.] Walter Reed Army Inst Res, US Mil HIV Res Program, Silver Spring, MD USA.
[Robb, Merlin L.; Eller, Leigh A.; Manak, Mark; Tovanabutra, Sodsai; Sanders-Buell, Eric; Rolland, Morgane; Dorsey-Spitz, Julie; Eller, Michael A.; Milazzo, Mark] Henry M Jackson Fdn Adv Mil Med, Rockville, MD USA.
[Swann, Edith] NIAID, Div Aids, NIH, Rockville, MD USA.
[Lewandowski, Andrew; Wu, Hao; Dawson, Peter] Emmes, Rockville, MD USA.
[Kibuuka, Hannah] Makerere Univ, Walter Reed Project, Kampala, Uganda.
[Rono, Kathleen; Sawe, Fred K.; Sinei, Samuel] Walter Reed Project, Kericho, Kenya.
[Maganga, Lucas] Mbeya Med Res Ctr, Mbeya, Tanzania.
[Nitayaphan, Sorachai; Kroon, Eugene; Sriplienchan, Somchai; de Souza, Mark S.; O'Connell, Robert J.] Armed Forces Res Inst Med Sci, Bangkok, Thailand.
[Kroon, Eugene; de Souza, Mark S.] SEARCH, Thai Red Cross AIDS Res Ctr, Bangkok, Thailand.
[Kim, Jerome H.] Int Vaccine Inst, Seoul, South Korea.
RP Robb, ML (reprint author), US Mil HIV Res Program, 6720A Rockledge Dr, Bethesda, MD 20817 USA.
EM mrobb@hivresearch.org
OI Manak, Mark /0000-0002-9217-9129
FU Department of Defense; National Institute of Allergy and Infectious
Diseases
FX Funded by the Department of Defense and the National Institute of
Allergy and Infectious Diseases.
NR 39
TC 12
Z9 12
U1 2
U2 3
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
EI 1533-4406
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD JUN 2
PY 2016
VL 374
IS 22
BP 2120
EP 2130
DI 10.1056/NEJMoa1508952
PG 11
WC Medicine, General & Internal
SC General & Internal Medicine
GA EB2RP
UT WOS:000387209900005
PM 27192360
ER
PT J
AU Ocampo, J
Chereji, RV
Eriksson, PR
Clark, DJ
AF Ocampo, Josefina
Chereji, Razvan V.
Eriksson, Peter R.
Clark, David J.
TI The ISW1 and CHD1 ATP-dependent chromatin remodelers compete to set
nucleosome spacing in vivo
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID TRANSCRIPTION ELONGATION-FACTORS; SACCHAROMYCES-CEREVISIAE; GENOME-WIDE;
LINKER HISTONE; ELECTROSTATIC MECHANISM; CODING REGIONS; YEAST GENOME;
GENES; RSC; H1
AB Adenosine triphosphate-dependent chromatin remodeling machines play a central role in gene regulation by manipulating chromatin structure. Most genes have a nucleosome-depleted region at the promoter and an array of regularly spaced nucleosomes phased relative to the transcription start site. In vitro, the three known yeast nucleosome spacing enzymes (CHD1, ISW1 and ISW2) form arrays with different spacing. We used genome-wide nucleosome sequencing to determine whether these enzymes space nucleosomes differently in vivo. We find that CHD1 and ISW1 compete to set the spacing onmost genes, such that CHD1 dominates genes with shorter spacing and ISW1 dominates genes with longer spacing. In contrast, ISW2 plays a minor role, limited to transcriptionally inactive genes. Heavily transcribed genes show weak phasing and extreme spacing, either very short or very long, and are depleted of linker histone (H1). Genes with longer spacing are enriched in H1, which directs chromatin folding. We propose that CHD1 directs short spacing, resulting in eviction of H1 and chromatin unfolding, whereas ISW1 directs longer spacing, allowing H1 to bind and condense the chromatin. Thus, competition between the two remodelers to set the spacing on each gene may result in a highly dynamic chromatin structure.
C1 [Ocampo, Josefina; Chereji, Razvan V.; Eriksson, Peter R.; Clark, David J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Dev Biol, NIH, Bethesda, MD 20892 USA.
RP Clark, DJ (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Dev Biol, NIH, Bethesda, MD 20892 USA.
EM clarkda@mail.nih.gov
OI Chereji, Razvan/0000-0002-0572-6412
FU Intramural Research Program of the NIH (NICHD)
FX Intramural Research Program of the NIH (NICHD). Funding for open access
charge: Intramural Research Program of the NIH (NICHD).
NR 62
TC 7
Z9 7
U1 3
U2 7
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
EI 1362-4962
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD JUN 2
PY 2016
VL 44
IS 10
BP 4625
EP 4635
DI 10.1093/nar/gkw068
PG 11
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA DR2SQ
UT WOS:000379754600021
PM 26861626
ER
PT J
AU Yin, JH
Wan, BB
Sarkar, J
Horvath, K
Wu, J
Chen, Y
Cheng, GJ
Wan, K
Chin, PJ
Lei, M
Liu, Y
AF Yin, Jinhu
Wan, Bingbing
Sarkar, Jaya
Horvath, Kent
Wu, Jian
Chen, Yong
Cheng, Guangjuan
Wan, Ke
Chin, Peiju
Lei, Ming
Liu, Yie
TI Dimerization of SLX4 contributes to functioning of the SLX4-nuclease
complex
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID HOLLIDAY JUNCTION RESOLUTION; DNA-REPAIR; FANCONI-ANEMIA; TELOMERE
MAINTENANCE; MAMMALIAN TELOMERES; GENOME MAINTENANCE; ENDONUCLEASES;
REPLICATION; NUCLEASES; DOMAIN
AB The Fanconi anemia protein SLX4 assembles a genome and telomere maintenance toolkit, consisting of the nucleases SLX1, MUS81 and XPF. Although it is known that SLX4 acts as a scaffold for building this complex, the molecular basis underlying this function of SLX4 remains unclear. Here, we report that functioning of SLX4 is dependent on its dimerization via an oligomerization motif called the BTB domain. We solved the crystal structure of the SLX4(BTB) dimer, identifying key contacts (F681 and F708) that mediate dimerization. Disruption of BTB dimerization abrogates nuclear foci formation and telomeric localization of not only SLX4 but also of its associated nucleases. Furthermore, dimerization-deficient SLX4 mutants cause defective cellular response to DNA interstrand crosslinking agent and telomere maintenance, underscoring the contribution of BTB domain-mediated dimerization of SLX4 in genome and telomere maintenance.
C1 [Yin, Jinhu; Sarkar, Jaya; Horvath, Kent; Chin, Peiju; Liu, Yie] NIA, Lab Mol Gerontol, NIH, 251 Bayview Blvd, Baltimore, MD 21044 USA.
[Wan, Bingbing; Wu, Jian; Chen, Yong; Lei, Ming] Chinese Acad Sci, Shanghai Inst Biol Sci, State Key Lab Mol Biol, Natl Ctr Prot Sci Shanghai,Inst Biochem & Cell Bi, 333 Haike Rd, Shanghai 200031, Peoples R China.
[Wan, Bingbing; Cheng, Guangjuan; Wan, Ke; Lei, Ming] Univ Michigan, Sch Med, Dept Biol Chem, 1150 W Med Ctr Dr, Ann Arbor, MI 48109 USA.
[Lei, Ming] Chinese Acad Sci, Shanghai Res Ctr, Shanghai 200031, Peoples R China.
RP Liu, Y (reprint author), NIA, Lab Mol Gerontol, NIH, 251 Bayview Blvd, Baltimore, MD 21044 USA.; Lei, M (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, State Key Lab Mol Biol, Natl Ctr Prot Sci Shanghai,Inst Biochem & Cell Bi, 333 Haike Rd, Shanghai 200031, Peoples R China.; Lei, M (reprint author), Univ Michigan, Sch Med, Dept Biol Chem, 1150 W Med Ctr Dr, Ann Arbor, MI 48109 USA.; Lei, M (reprint author), Chinese Acad Sci, Shanghai Res Ctr, Shanghai 200031, Peoples R China.
EM leim@sibcb.ac.cn; liuyie@mail.nih.gov
FU Intramural Research Program of the National Institutes of Health,
National Institute on Aging; Ministry of Science and Technology of China
[2013CB910402]; National Natural Science Foundation of China [31330040];
Strategic Priority Research Program of the Chinese Academy of Sciences
[XDB08010201]; U.S. Department of Energy, Office of Science, Office of
Basic Energy Sciences [DE-AC02-06CH11357]
FX Intramural Research Program of the National Institutes of Health,
National Institute on Aging; Ministry of Science and Technology of China
[2013CB910402 to M.L.]; National Natural Science Foundation of China
[31330040 to M.L.]; Strategic Priority Research Program of the Chinese
Academy of Sciences [XDB08010201 to M.L.]; U.S. Department of Energy,
Office of Science, Office of Basic Energy Sciences [DE-AC02-06CH11357].
Funding for open access charge: Intramural Research Program of the
National Institutes of Health, National Institute on Aging; Ministry of
Science and Technology of China [2013CB910402 to M.L.]; National Natural
Science Foundation of China [31330040 to M.L.]; Strategic Priority
Research Program of the Chinese Academy of Sciences [XDB08010201 to
M.L.].
NR 31
TC 1
Z9 1
U1 2
U2 2
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
EI 1362-4962
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD JUN 2
PY 2016
VL 44
IS 10
BP 4871
EP 4880
DI 10.1093/nar/gkw354
PG 10
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA DR2SQ
UT WOS:000379754600037
PM 27131364
ER
PT J
AU Wang, R
Luo, ZP
He, KZ
Delaney, MO
Chen, D
Sheng, J
AF Wang, Rui
Luo, Zhipu
He, Kaizhang
Delaney, Michael O.
Chen, Doris
Sheng, Jia
TI Base pairing and structural insights into the 5-formylcytosine in RNA
duplex
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID MITOCHONDRIAL TRNA(MET); OXIDATIVE DEMETHYLATION; CIRCULAR-DICHROISM;
ESCHERICHIA-COLI; NONCODING RNA; DNA; 5-HYDROXYMETHYLCYTOSINE;
5-METHYLCYTOSINE; ANTICODON; SEQUENCE
AB 5-Formylcytidine (f(5)C), a previously discovered natural nucleotide in the mitochondrial tRNA of many species including human, has been recently detected as the oxidative product of 5-methylcytidine (m(5)C) through 5-hydroxymethylcytidine (hm(5)C) in total RNA of mammalian cells. The discovery indicated that these cytosine derivatives in RNA might also play important epigenetic roles similar as in DNA, which has been intensively investigated in the past few years. In this paper, we studied the base pairing specificity of f(5)C in different RNA duplex contexts. We found that the 5-formyl group could increase duplex thermal stability and enhance base pairing specificity. We present three high-resolution crystal structures of an octamer RNA duplex [5'-GUA(f(5)C)GUAC-3'](2) that have been solved under three crystallization conditions with different buffers and pH values. Our results showed that the 5-formyl group is located in the same plane as the cytosine base and forms an intra-residue hydrogen bond with the amino group in the N4 position. In addition, this modification increases the base stacking between the f(5)C and the neighboring bases while not causing significant global and local structure perturbations. This work provides insights into the effects of 5-formylcytosine on RNA duplex.
C1 [Wang, Rui; Chen, Doris; Sheng, Jia] SUNY Albany, Dept Chem, Albany, NY 12222 USA.
[Wang, Rui; Chen, Doris; Sheng, Jia] SUNY Albany, RNA Inst, Albany, NY 12222 USA.
[Luo, Zhipu] Argonne Natl Lab, Synchrotron Radiat Res Sect, MCL Natl Canc Inst, Argonne, IL 60439 USA.
[He, Kaizhang; Delaney, Michael O.] GE Healthcare, Dharmacon, Lafayette, CO 80026 USA.
RP Sheng, J (reprint author), SUNY Albany, Dept Chem, Albany, NY 12222 USA.; Sheng, J (reprint author), SUNY Albany, RNA Inst, Albany, NY 12222 USA.
EM jsheng@albany.edu
FU University at Albany, State University of New York start-up fund; Simons
Foundation Postdoctoral Fellowship [338863]; U.S. Department of Energy,
Office of Science, Office of Basic Energy Sciences [W-31-109-Eng-38]
FX University at Albany, State University of New York start-up fund; Simons
Foundation Postdoctoral Fellowship [338863 to R. W.]; U.S. Department of
Energy, Office of Science, Office of Basic Energy Sciences,
[W-31-109-Eng-38]. Funding for open access charge: University at Albany,
State University of New York start-up fund.
NR 61
TC 0
Z9 0
U1 8
U2 11
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
EI 1362-4962
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD JUN 2
PY 2016
VL 44
IS 10
BP 4968
EP 4977
DI 10.1093/nar/gkw235
PG 10
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA DR2SQ
UT WOS:000379754600045
PM 27079978
ER
PT J
AU Goldenberg, RL
Thorsten, VR
Althabe, F
Saleem, S
Garces, A
Carlo, WA
Pasha, O
Chomba, E
Goudar, S
Esamai, F
Krebs, NF
Derman, RJ
Liechty, EA
Patel, A
Hibberd, PL
Buekens, PM
Koso-Thomas, M
Miodovnik, M
Jobe, AH
Wallace, DD
Belizan, JM
McClure, EM
AF Goldenberg, Robert L.
Thorsten, Vanessa R.
Althabe, Fernando
Saleem, Sarah
Garces, Ana
Carlo, Waldemar A.
Pasha, Omrana
Chomba, Elwyn
Goudar, Shivaprasad
Esamai, Fabian
Krebs, Nancy F.
Derman, Richard J.
Liechty, Edward A.
Patel, Archana
Hibberd, Patricia L.
Buekens, Pierre M.
Koso-Thomas, Marion
Miodovnik, Menachem
Jobe, Alan H.
Wallace, Dennis D.
Belizan, Jose M.
McClure, Elizabeth M.
TI The global network antenatal corticosteroids trial: impact on stillbirth
SO REPRODUCTIVE HEALTH
LA English
DT Article
ID MIDDLE-INCOME COUNTRIES; PRETERM BIRTH; NEONATAL DEATH; RISK;
MULTICOUNTRY; PREGNANCY; WOMEN
AB Background: Antenatal corticosteroids are commonly used to reduce neonatal mortality, but most research to date has been in high-resource settings and few studies have evaluated its impact on stillbirth. In the Antenatal Corticosteroids Trial (ACT), a multi-country trial to assess impact of a multi-faceted intervention including antenatal corticosteroids to reduce neonatal mortality associated with preterm birth, we found an overall increase in 28-day neonatal mortality and stillbirth associated with the intervention.
Methods: The ACT was a cluster-randomized trial conducted in 102 clusters across 7 research sites in 6 countries (India [ 2 sites], Pakistan, Zambia, Kenya, Guatemala and Argentina), comparing an intervention to train birth attendants at all levels of the health system to identify women at risk of preterm birth, administer corticosteroids and refer women at risk. Because of inadequate gestational age dating, the <5th percentile birth weight was used as a proxy for preterm birth. A pre-specified secondary outcome of the trial was stillbirth.
Results: After adjusting for the pre-trial imbalance in stillbirth rates, the ACT intervention was associated with a non-significant increased risk of stillbirth (aRR 1.08, 95 % CI, 0.99-1.17, p-0.073). Additionally, the stillbirth rate was higher in the term births (1.20 95 % CI 1.06-1.37, 0.004) and among those with signs of maceration (RR 1.18 (1.04-1.35), p = 0.013) in the intervention vs. control clusters. Differences in obstetric care favored the control clusters and maternal infection was likely more common in the intervention clusters.
Conclusions: In this pragmatic trial, limited data were available to identify the causes of the increase in stillbirths in the intervention clusters. A higher rate of stillbirth in the intervention clusters prior to the trial, differences in obstetric care and an increase in maternal infection are potential explanations for the observed increase in stillbirths in the intervention clusters during the trial.
C1 [Goldenberg, Robert L.; Saleem, Sarah] Columbia Univ, New York, NY USA.
[Thorsten, Vanessa R.; Wallace, Dennis D.; McClure, Elizabeth M.] RTI Int, Durham, NC USA.
[Althabe, Fernando; Belizan, Jose M.] IECS, Buenos Aires, DF, Argentina.
[Saleem, Sarah; Pasha, Omrana] Aga Khan Univ, Karachi, Pakistan.
[Carlo, Waldemar A.] Univ Alabama Birmingham, Birmingham, AL USA.
[Chomba, Elwyn] Univ Teaching Hosp, Lusaka, Zambia.
[Goudar, Shivaprasad] KLE Univ JN Med Coll, Belgaum, India.
[Esamai, Fabian] Moi Univ, Eldoret, Kenya.
[Krebs, Nancy F.] Univ Colorado, Sch Med, Denver, CO USA.
[Derman, Richard J.] Christiana Care, Newark, DE USA.
[Liechty, Edward A.] Indiana Univ, Indianapolis, IN 46204 USA.
[Patel, Archana] Lata Med Res Fdn, Nagpur, Maharashtra, India.
[Hibberd, Patricia L.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Buekens, Pierre M.] Tulane Sch Publ Hlth & Trop Med, New Orleans, LA USA.
[Koso-Thomas, Marion; Miodovnik, Menachem] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA.
[Jobe, Alan H.] Cincinnati Childrens Hosp, Cincinnati, OH USA.
[Goldenberg, Robert L.] Columbia Univ, Dept Obstet & Gynecol, New York, NY USA.
RP Goldenberg, RL (reprint author), Columbia Univ, New York, NY USA.; Goldenberg, RL (reprint author), Columbia Univ, Dept Obstet & Gynecol, New York, NY USA.
EM rlg@columbia.edu
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development [U01 HD058322, U01 HD040477, U01 HD043464, U01 HD040657, U01
HD042372, U01 HD040607, U01 HD058326, U01 HD040636]; Bill and Melinda
Gates Foundation
FX This trial was funded through grants from the Eunice Kennedy Shriver
National Institute of Child Health and Human Development (U01 HD058322,
U01 HD040477, U01 HD043464, U01 HD040657, U01 HD042372, U01 HD040607,
U01 HD058326, U01 HD040636). Additional support was also provided by the
Bill and Melinda Gates Foundation (FA, KK, JMB)
NR 13
TC 0
Z9 0
U1 1
U2 1
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1742-4755
J9 REPROD HEALTH
JI Reprod. Health
PD JUN 2
PY 2016
VL 13
AR 68
DI 10.1186/s12978-016-0174-4
PG 10
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA DP6OU
UT WOS:000378617300001
PM 27255082
ER
PT J
AU Knittel, G
Liedgens, P
Korovkina, D
Seeger, JM
Al-Baldawi, Y
Al-Maarri, M
Fritz, C
Vlantis, K
Bezhanova, S
Scheel, AH
Wolz, OO
Reimann, M
Moller, P
Lopez, C
Schlesner, M
Lohneis, P
Weber, ANR
Trumper, L
Staudt, LM
Ortmann, M
Pasparakis, M
Siebert, R
Schmitt, CA
Klatt, AR
Wunderlich, FT
Schafer, SC
Persigehl, T
Montesinos-Rongen, M
Odenthal, M
Buttner, R
Frenzel, LP
Kashkar, H
Reinhardt, HC
AF Knittel, Gero
Liedgens, Paul
Korovkina, Darya
Seeger, Jens M.
Al-Baldawi, Yussor
Al-Maarri, Mona
Fritz, Christian
Vlantis, Katerina
Bezhanova, Svetlana
Scheel, Andreas H.
Wolz, Olaf-Oliver
Reimann, Maurice
Moeller, Peter
Lopez, Cristina
Schlesner, Matthias
Lohneis, Philipp
Weber, Alexander N. R.
Truemper, Lorenz
Staudt, Louis M.
Ortmann, Monika
Pasparakis, Manolis
Siebert, Reiner
Schmitt, Clemens A.
Klatt, Andreas R.
Wunderlich, F. Thomas
Schaefer, Stephan C.
Persigehl, Thorsten
Montesinos-Rongen, Manuel
Odenthal, Margarete
Buettner, Reinhard
Frenzel, Lukas P.
Kashkar, Hamid
Reinhardt, H. Christian
CA German Int Canc Genome Consortium
Mol Mech Malignant Lymphoma Sequen
TI B-cell-specific conditional expression of Myd88(p.L252P) leads to the
development of diffuse large B-cell lymphoma in mice
SO BLOOD
LA English
DT Article
ID CHRONIC LYMPHOCYTIC-LEUKEMIA; IDENTIFIES RECURRENT MUTATIONS;
WALDENSTROM MACROGLOBULINEMIA; SOMATIC MUTATION; GERMINAL CENTER; MYD88
L265P; GENE; DIFFERENTIATION; CLASSIFICATION; ACTIVATION
AB The adaptor protein MYD88 is critical for relaying activation of Toll-like receptor signaling to NF-kappa B activation. MYD88 mutations, particularly the p.L265P mutation, have been described in numerous distinct B-cell malignancies, including diffuse large B-cell lymphoma (DLBCL). Twenty-nine percent of activated B-cell-type DLBCL (ABC-DLBCL), which is characterized by constitutive activation of the NF-kappa B pathway, carry the p.L265P mutation. In addition, ABC-DLBCL frequently displays focal copy number gains affecting BCL2. Here, we generated a novel mouse model in which Cre-mediated recombination, specifically in B cells, leads to the conditional expression of Myd88(p.L252P) (the orthologous position of the human MYD88(p.L265P) mutation) from the endogenous locus. These mice develop a lymphoproliferative disease and occasional transformation into clonal lymphomas. The clonal disease displays the morphologic and immunophenotypical characteristics of ABC-DLBCL. Lymphomagenesis can be accelerated by crossing in a further novel allele, which mediates conditional overexpression of BCL2. Cross-validation experiments in human DLBCL samples revealed that both MYD88 and CD79B mutations are substantially enriched in ABC-DLBCL compared with germinal center B-cell DLBCL. Furthermore, analyses of human DLBCL genome sequencing data confirmed that BCL2 amplifications frequently co-occurred with MYD88 mutations, further validating our approach. Finally, in silico experiments revealed that MYD88-mutant ABC-DLBCL cells in particular display an actionable addiction to BCL2. Altogether, we generated a novel autochthonous mouse model of ABC-DLBCL that could be used as a preclinical platform for the development and validation of novel therapeutic approaches for the treatment of ABC-DLBCL.
C1 [Knittel, Gero; Liedgens, Paul; Korovkina, Darya; Fritz, Christian; Frenzel, Lukas P.; Reinhardt, H. Christian] Univ Hosp Cologne, Dept Internal Med 1, Weyertal 115B, D-50931 Cologne, Germany.
[Knittel, Gero; Liedgens, Paul; Korovkina, Darya; Seeger, Jens M.; Fritz, Christian; Vlantis, Katerina; Pasparakis, Manolis; Frenzel, Lukas P.; Kashkar, Hamid; Reinhardt, H. Christian] Univ Cologne, Cologne Excellence Cluster Cellular Stress Respon, D-50931 Cologne, Germany.
[Seeger, Jens M.; Kashkar, Hamid] Univ Hosp Cologne, Fac Med, Inst Microbiol & Hyg, D-50931 Cologne, Germany.
[Al-Baldawi, Yussor; Persigehl, Thorsten] Univ Hosp Cologne, Fac Med, Dept Radiol, D-50931 Cologne, Germany.
[Al-Maarri, Mona; Wunderlich, F. Thomas] Max Planck Inst Metab Res, Cologne, Germany.
[Bezhanova, Svetlana; Scheel, Andreas H.; Ortmann, Monika; Schaefer, Stephan C.; Odenthal, Margarete; Buettner, Reinhard] Univ Hosp Cologne, Inst Pathol, D-50931 Cologne, Germany.
[Bezhanova, Svetlana] NN Blokhin Russian Canc Res Ctr, Moscow, Russia.
[Wolz, Olaf-Oliver; Weber, Alexander N. R.] Univ Tubingen, Dept Immunol, Interfac Inst Cell Biol, Tubingen, Germany.
[Reimann, Maurice; Schmitt, Clemens A.] Charite Univ Med Ctr, Dept Hematol Oncol, Berlin, Germany.
[Moeller, Peter] Univ Ulm, Fac Med, Inst Pathol, D-89069 Ulm, Germany.
[Lopez, Cristina; Siebert, Reiner] Univ Kiel, Inst Human Genet, Kiel, Germany.
[Lopez, Cristina; Siebert, Reiner] Univ Hosp Schleswig Holstein, Kiel, Germany.
[Schlesner, Matthias] German Canc Res Ctr, Dept Theoret Bioinformat, Heidelberg, Germany.
[Lohneis, Philipp] Charite Univ Med Ctr, Dept Pathol, Berlin, Germany.
[Truemper, Lorenz] Univ Gottingen, Dept Hematol & Oncol, Gottingen, Germany.
[Staudt, Louis M.] NCI, Metab Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Schmitt, Clemens A.] Helmholtz Assoc, Max Delbruck Ctr Mol Med, Berlin, Germany.
[Klatt, Andreas R.] Univ Hosp Cologne, Inst Clin Chem, D-50931 Cologne, Germany.
[Montesinos-Rongen, Manuel] Univ Hosp Cologne, Inst Neuropathol, D-50931 Cologne, Germany.
[Odenthal, Margarete; Buettner, Reinhard; Frenzel, Lukas P.; Reinhardt, H. Christian] Univ Hosp Cologne, Ctr Integrated Oncol, D-50931 Cologne, Germany.
[Buettner, Reinhard; Kashkar, Hamid; Reinhardt, H. Christian] Univ Cologne, Ctr Mol Med, D-50931 Cologne, Germany.
RP Reinhardt, HC (reprint author), Univ Hosp Cologne, Dept Internal Med 1, Weyertal 115B, D-50931 Cologne, Germany.
EM christian.reinhardt@uk-koeln.de
RI Siebert, Reiner/A-8049-2010
FU Volkswagenstiftung (Lichtenberg Program); Deutsche
Forschungsgemeinschaft [KFO-286, KA 2853/4-1, SFB-685]; Deutsche Jose
Carreras Leukamie Stiftung [R12/26]; Marga und Walter Boll Stiftung
[210-05-13]; Helmholtz-Gemeinschaft (Preclinical Comprehensive Cancer
Center); Else Kroner-Fresenius Stiftung [EKFS-2014-A06]; Marlene Porsche
Foundation for Cancer Prevention; Else-Ubelmesser Stiftung
(Juniorprofessoren-Programn); Deutsche Krebshilfe [111724]; German
Ministry of Science and Education in the framework of the International
CancerGenome Consortium Molecular Mechanisms in Malignant Lymphoma by
Sequencing Project [01KU1002A-J]
FX This work was supported by the Volkswagenstiftung (Lichtenberg Program
[H.C.R.]), the Deutsche Forschungsgemeinschaft (KFO-286 [H.C.R., H.K.,
F.T.W., and L.P.F.], KA 2853/4-1 [H.K.], and SFB-685 [A.N.R.W.,
O.-O.W.]), the Deutsche Jose Carreras Leukamie Stiftung (R12/26 [H.C.R.
and L.P.F.]), the Marga und Walter Boll Stiftung (210-05-13 [L.P.F.]),
the Helmholtz-Gemeinschaft (Preclinical Comprehensive Cancer Center
[H.C.R. and C.A.S.]), the Else Kroner-Fresenius Stiftung (EKFS-2014-A06
[H.C.R.]), the Marlene Porsche Foundation for Cancer Prevention (S.B.),
the Else-Ubelmesser Stiftung (Juniorprofessoren-Programn [A.N.R.W]), the
Deutsche Krebshilfe (111724 [H.C.R.]), and the German Ministry of
Science and Education in the framework of the International CancerGenome
Consortium Molecular Mechanisms in Malignant Lymphoma by Sequencing
Project (01KU1002A-J [C.L., P.M., L.T., and R.S.]).
NR 56
TC 6
Z9 6
U1 1
U2 4
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA
SN 0006-4971
EI 1528-0020
J9 BLOOD
JI Blood
PD JUN 2
PY 2016
VL 127
IS 22
BP 2732
EP 2741
DI 10.1182/blood-2015-11684183
PG 10
WC Hematology
SC Hematology
GA DP2QS
UT WOS:000378335400015
PM 27048211
ER
PT J
AU Green, RC
Goddard, KAB
Jarvik, GP
Amendola, LM
Appelbaum, PS
Berg, JS
Bernhardt, BA
Biesecker, LG
Biswas, S
Blout, CL
Bowling, KM
Brothers, KB
Burke, W
Caga-anan, CF
Chinnaiyan, AM
Chung, WK
Clayton, EW
Cooper, GM
East, K
Evans, JP
Fullerton, SM
Garraway, LA
Garrett, JR
Gray, SW
Henderson, GE
Hindorff, LA
Holm, IA
Lewis, MH
Hutter, CM
Janne, PA
Joffe, S
Kaufman, D
Knoppers, BM
Koenig, BA
Krantz, ID
Manolio, TA
McCullough, L
McEwen, J
McGuire, A
Muzny, D
Myers, RM
Nickerson, DA
Ou, J
Parsons, DW
Petersen, GM
Plon, SE
Rehm, HL
Roberts, JS
Robinson, D
Salama, JS
Scollon, S
Sharp, RR
Shirts, B
Spinner, NB
Tabor, HK
Tarczy-Hornoch, P
Veenstra, DL
Wagle, N
Weck, K
Wilfond, BS
Wilhelmsen, K
Wolf, SM
Wynn, J
Yu, JH
AF Green, Robert C.
Goddard, Katrina A. B.
Jarvik, Gail P.
Amendola, Laura M.
Appelbaum, Paul S.
Berg, Jonathan S.
Bernhardt, Barbara A.
Biesecker, Leslie G.
Biswas, Sawona
Blout, Carrie L.
Bowling, Kevin M.
Brothers, Kyle B.
Burke, Wylie
Caga-anan, Charlisse F.
Chinnaiyan, Arul M.
Chung, Wendy K.
Clayton, Ellen W.
Cooper, Gregory M.
East, Kelly
Evans, James P.
Fullerton, Stephanie M.
Garraway, Levi A.
Garrett, Jeremy R.
Gray, Stacy W.
Henderson, Gail E.
Hindorff, Lucia A.
Holm, Ingrid A.
Lewis, Michelle Huckaby
Hutter, Carolyn M.
Janne, Pasi A.
Joffe, Steven
Kaufman, David
Knoppers, Bartha M.
Koenig, Barbara A.
Krantz, Ian D.
Manolio, Teri A.
McCullough, Laurence
McEwen, Jean
McGuire, Amy
Muzny, Donna
Myers, Richard M.
Nickerson, Deborah A.
Ou, Jeffrey
Parsons, Donald W.
Petersen, Gloria M.
Plon, Sharon E.
Rehm, Heidi L.
Roberts, J. Scott
Robinson, Dan
Salama, Joseph S.
Scollon, Sarah
Sharp, Richard R.
Shirts, Brian
Spinner, Nancy B.
Tabor, Holly K.
Tarczy-Hornoch, Peter
Veenstra, David L.
Wagle, Nikhil
Weck, Karen
Wilfond, Benjamin S.
Wilhelmsen, Kirk
Wolf, Susan M.
Wynn, Julia
Yu, Joon-Ho
CA CSER Consortium
TI Clinical Sequencing Exploratory Research Consortium: Accelerating
Evidence-Based Practice of Genomic Medicine
SO AMERICAN JOURNAL OF HUMAN GENETICS
LA English
DT Article
ID OBTAINING INFORMED-CONSENT; GENETIC RESEARCH FINDINGS; ELECTRONIC HEALTH
RECORD; INCIDENTAL-FINDINGS; WHOLE-EXOME; MEDSEQ PROJECT; RESEARCH
PARTICIPANTS; ACMG RECOMMENDATIONS; BEHAVIORAL ECONOMICS; PERCEIVED
UTILITY
AB Despite rapid technical progress and demonstrable effectiveness for some types of diagnosis and therapy, much remains to be learned about clinical genome and exome sequencing (CGES) and its role within the practice of medicine. The Clinical Sequencing Exploratory Research (CSER) consortium includes 18 extramural research projects, one National Human Genome Research Institute (NHGRI) intramural project, and a coordinating center funded by the NHGRI and National Cancer Institute. The consortium is exploring analytic and clinical validity and utility, as well as the ethical, legal, and social implications of sequencing via multidisciplinary approaches; it has thus far recruited 5,577 participants across a spectrum of symptomatic and healthy children and adults by utilizing both germline and cancer sequencing. The CSER consortium is analyzing data and creating publically available procedures and tools related to participant preferences and consent, variant classification, disclosure and management of primary and secondary findings, health outcomes, and integration with electronic health records. Future research directions will refine measures of clinical utility of CGES in both germline and somatic testing, evaluate the use of CGES for screening in healthy individuals, explore the penetrance of pathogenic variants through extensive phenotyping, reduce discordances in public databases of genes and variants, examine social and ethnic disparities in the provision of genomics services, explore regulatory issues, and estimate the value and downstreamcosts of sequencing. The CSER consortium has established a shared community of research sites by using diverse approaches to pursue the evidence-based development of best practices in genomic medicine.
C1 [Green, Robert C.; Blout, Carrie L.] Brigham & Womens Hosp, Dept Med, Div Genet, 75 Francis St, Boston, MA 02115 USA.
[Green, Robert C.; Garraway, Levi A.; Rehm, Heidi L.; Wagle, Nikhil] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.
[Green, Robert C.; Gray, Stacy W.; Holm, Ingrid A.; Janne, Pasi A.; Rehm, Heidi L.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Green, Robert C.; Rehm, Heidi L.] Partners Personalized Med, Boston, MA 02139 USA.
[Goddard, Katrina A. B.] Kaiser Permanente Northwest, Ctr Hlth Res, Portland, OR 97227 USA.
[Jarvik, Gail P.; Nickerson, Deborah A.] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA.
[Jarvik, Gail P.; Amendola, Laura M.; Burke, Wylie; Ou, Jeffrey; Salama, Joseph S.; Tarczy-Hornoch, Peter] Univ Washington, Dept Med, Div Med Genet, Seattle, WA 98195 USA.
[Jarvik, Gail P.; Amendola, Laura M.; Burke, Wylie; Ou, Jeffrey; Salama, Joseph S.] Univ Washington, Clin Sequencing Exploratory Res Coordinating Ctr, Seattle, WA 98195 USA.
[Appelbaum, Paul S.] Columbia Univ, Med Ctr, Dept Psychiat, New York, NY 10032 USA.
[Appelbaum, Paul S.] New York State Psychiat Inst & Hosp, New York, NY 10032 USA.
[Berg, Jonathan S.; Evans, James P.; Weck, Karen; Wilhelmsen, Kirk] Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA.
[Bernhardt, Barbara A.; Biswas, Sawona; Krantz, Ian D.; Spinner, Nancy B.] Univ Penn, Perelman Sch Med, Dept Med, Div Translat Med & Human Genet, Philadelphia, PA 19104 USA.
[Biesecker, Leslie G.] NHGRI, Med Genom & Metab Genet Branch, NIH, Bethesda, MD 20892 USA.
[Biswas, Sawona; Krantz, Ian D.] Childrens Hosp Philadelphia, Dept Pediat, Philadelphia, PA 19104 USA.
[Bowling, Kevin M.; Cooper, Gregory M.; East, Kelly; Myers, Richard M.] HudsonAlpha Inst Biotechnol, Huntsville, AL 35806 USA.
[Brothers, Kyle B.] Univ Louisville, Dept Pediat, Louisville, KY 40202 USA.
[Burke, Wylie; Fullerton, Stephanie M.] Univ Washington, Dept Med, Dept Bioeth & Humanities, Seattle, WA 98195 USA.
[Caga-anan, Charlisse F.] NCI, NIH, Bethesda, MD 20892 USA.
[Chinnaiyan, Arul M.; Robinson, Dan] Michigan Ctr Translat Pathol, Ann Arbor, MI 48109 USA.
[Chinnaiyan, Arul M.] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA.
[Chinnaiyan, Arul M.] Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA.
[Chinnaiyan, Arul M.] Univ Michigan, Dept Urol, Ann Arbor, MI 48109 USA.
[Chinnaiyan, Arul M.] Howard Hughes Med Inst, Ann Arbor, MI 48109 USA.
[Chung, Wendy K.; Wynn, Julia] Columbia Univ, Dept Pediat, New York, NY 10029 USA.
[Chung, Wendy K.] Columbia Univ, Med Ctr, Dept Med, New York, NY 10032 USA.
[Clayton, Ellen W.] Vanderbilt Univ, Ctr Biomed Eth & Soc, Nashville, TN 37203 USA.
[Garraway, Levi A.; Wagle, Nikhil] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Garraway, Levi A.; Wagle, Nikhil] Dana Farber Canc Inst, Ctr Canc Precis Med, Boston, MA 02115 USA.
[Garraway, Levi A.; Wagle, Nikhil] Brigham & Womens Hosp, Dept Med, 75 Francis St, Boston, MA 02115 USA.
[Garrett, Jeremy R.] Childrens Mercy Hosp, Childrens Mercy Bioeth Ctr, Kansas City, MO 64108 USA.
[Garrett, Jeremy R.] Univ Missouri, Dept Pediat, Kansas City, MO 64110 USA.
[Garrett, Jeremy R.] Univ Missouri, Dept Philosophy, Kansas City, MO 64110 USA.
[Gray, Stacy W.; Janne, Pasi A.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Henderson, Gail E.] Univ N Carolina, Sch Med, Dept Social Med, Chapel Hill, NC 27599 USA.
[Hindorff, Lucia A.; Hutter, Carolyn M.; Manolio, Teri A.] NHGRI, Div Genom Med, NIH, Bethesda, MD 20892 USA.
[Holm, Ingrid A.] Boston Childrens Hosp, Div Genet & Genom, Boston, MA 02115 USA.
[Holm, Ingrid A.] Boston Childrens Hosp, Manton Ctr Orphan Dis Res, Boston, MA 02115 USA.
[Lewis, Michelle Huckaby] Johns Hopkins, Berman Inst Bioeth, Baltimore, MD 21205 USA.
[Joffe, Steven; McGuire, Amy] Univ Penn, Sch Med, Dept Med Eth & Hlth Policy, Philadelphia, PA 19104 USA.
[Kaufman, David; McEwen, Jean] NHGRI, Div Genom & Soc, NIH, Bethesda, MD 20892 USA.
[Knoppers, Bartha M.] McGill Univ, Dept Human Genet, Fac Med, Ctr Genom & Policy, Montreal, PQ H3A 1B1, Canada.
[Koenig, Barbara A.] Univ Calif San Francisco, Inst Hlth & Aging, San Francisco, CA 94118 USA.
[McCullough, Laurence; McGuire, Amy] Baylor Coll Med, Ctr Med Eth & Hlth Policy, Houston, TX 77030 USA.
[Muzny, Donna] Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA.
[Parsons, Donald W.; Plon, Sharon E.] Baylor Coll Med, Houston, TX 77030 USA.
[Parsons, Donald W.; Plon, Sharon E.] Texas Childrens Canc Ctr, Houston, TX 77030 USA.
[Petersen, Gloria M.] Mayo Clin, Coll Med, Dept Hlth Sci Res, Rochester, MN 55905 USA.
[Rehm, Heidi L.] Partners HealthCare, Mol Med Lab, Cambridge, MA 02139 USA.
[Roberts, J. Scott] Univ Michigan, Sch Publ Hlth, Dept Hlth Behav & Hlth Educ, Ann Arbor, MI 48109 USA.
[Scollon, Sarah] Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA.
[Sharp, Richard R.] Mayo Clin, Coll Med, Biomed Eth Res Program, Rochester, MN 55905 USA.
[Shirts, Brian] Univ Washington, Dept Lab Med, Seattle, WA 98195 USA.
[Spinner, Nancy B.] Childrens Hosp Philadelphia, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA.
[Tabor, Holly K.; Wilfond, Benjamin S.; Yu, Joon-Ho] Univ Washington, Dept Pediat, Seattle, WA 98195 USA.
[Tabor, Holly K.; Wilfond, Benjamin S.] Univ Washington, Seattle Childrens Res Inst, Seattle, WA 98195 USA.
[Tarczy-Hornoch, Peter] Univ Washington, Seattle, WA 98105 USA.
[Veenstra, David L.] Univ Washington, Dept Pharm, Seattle, WA 98195 USA.
[Weck, Karen] Univ N Carolina, Dept Pathol & Lab Med, Chapel Hill, NC 27599 USA.
[Wolf, Susan M.] Univ Minnesota, Sch Med, Sch Law, Minneapolis, MN 55455 USA.
[Wolf, Susan M.] Univ Minnesota, Consortium Law & Values Hlth Environm & Life Sci, Minneapolis, MN 55455 USA.
RP Green, RC (reprint author), Brigham & Womens Hosp, Dept Med, Div Genet, 75 Francis St, Boston, MA 02115 USA.; Green, RC (reprint author), Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.; Green, RC (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA.; Green, RC (reprint author), Partners Personalized Med, Boston, MA 02139 USA.
EM rcgreen@genetics.med.harvard.edu
OI Tarczy-Hornoch, Peter/0000-0003-1047-179X; Lebo,
Matthew/0000-0002-9733-5207; Seifert, Bryce/0000-0001-7970-3611
FU NHGRI; [U01HG0006546]; [U01HG006485]; [U01HG006500]; [U01HG006492];
[UM1HG007301]; [UM1HG007292]; [UM1HG006508]; [U01HG006487];
[U01HG006507]; [U01HG007307]; [U01HG006379]; [U41HG006834];
[U54HG003273]; [R21HG006596]; [P20HG007243]; [P50HG007257];
[R01HG006600]; [R01HG004500]; [R01CA154517]; [R01HG006618];
[R21HG006594]; [R01HG006615]; [R21HG006612]; [5R21HG006613];
[R01HG007063]; [HG008685]; [UL1TR000423]; [UA01AG047109];
[K99HG007076]
FX The authors thank Julia Fekecs of the National Human Genome Research
Institute (NHGRI) for her technical assistance with Figure 1. The
authors would like to thank all of the Clinical Sequencing Exploratory
Research (CSER) participants for their involvement in this research. The
authors also thank the members of their CSER advisory panel: Katrina
Armstrong, MD; Rex L. Chisholm, PhD; Mildred K. Cho, PhD; Chanita H.
Halbert, PhD; Elaine Lyon, PhD; Kenneth Offit, MD; Dan Roden, MD; Pamela
Sankar, PhD; and Alan Williamson, PhD. The research described in this
report was funded by grants U01HG0006546, U01HG006485, U01HG006500,
U01HG006492, UM1HG007301, UM1HG007292, UM1HG006508, U01HG006487,
U01HG006507, U01HG007307, U01HG006379, U41HG006834, U54HG003273,
R21HG006596, P20HG007243, R01HG006600, P50HG007257, R01HG006600,
R01HG004500, R01CA154517, R01HG006618, R21HG006594, R01HG006615,
R21HG006612, 5R21HG006613, R01HG007063, HG008685, UL1TR000423,
UA01AG047109, and K99HG007076. ClinSeq is supported by the NHGRI
Intramural Research Program. C.F.C.-A., L.A.H., C.M.H., D.K., T.A.M.,
and J.M. are members of the NIH CSER staff team, responsible for
management of the CSER program.
NR 109
TC 12
Z9 12
U1 5
U2 11
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0002-9297
EI 1537-6605
J9 AM J HUM GENET
JI Am. J. Hum. Genet.
PD JUN 2
PY 2016
VL 98
IS 6
BP 1051
EP 1066
DI 10.1016/j.ajhg.2016.04.011
PG 16
WC Genetics & Heredity
SC Genetics & Heredity
GA DN7US
UT WOS:000377286000001
PM 27181682
ER
PT J
AU Amendola, LM
Jarvik, GP
Leo, MC
McLaughlin, HM
Akkari, Y
Amaral, MD
Berg, JS
Biswas, S
Bowling, KM
Conlin, LK
Cooper, GM
Dorschner, MO
Dulik, MC
Ghazani, AA
Ghosh, R
Green, RC
Hart, R
Horton, C
Johnston, JJ
Lebo, MS
Milosavljevic, A
Ou, J
Pak, CM
Patel, RY
Punj, S
Richards, CS
Salama, J
Strande, NT
Yang, YP
Plon, SE
Biesecker, LG
Rehm, HL
AF Amendola, Laura M.
Jarvik, Gail P.
Leo, Michael C.
McLaughlin, Heather M.
Akkari, Yassmine
Amaral, Michelle D.
Berg, Jonathan S.
Biswas, Sawona
Bowling, Kevin M.
Conlin, Laura K.
Cooper, Greg M.
Dorschner, Michael O.
Dulik, Matthew C.
Ghazani, Arezou A.
Ghosh, Rajarshi
Green, Robert C.
Hart, Ragan
Horton, Carrie
Johnston, Jennifer J.
Lebo, Matthew S.
Milosavljevic, Aleksandar
Ou, Jeffrey
Pak, Christine M.
Patel, Ronak Y.
Punj, Sumit
Richards, Carolyn Sue
Salama, Joseph
Strande, Natasha T.
Yang, Yaping
Plon, Sharon E.
Biesecker, Leslie G.
Rehm, Heidi L.
TI Performance of ACMG-AMP Variant-Interpretation Guidelines among Nine
Laboratories in the Clinical Sequencing Exploratory Research Consortium
SO AMERICAN JOURNAL OF HUMAN GENETICS
LA English
DT Article
ID SPASTIC PARAPLEGIA; GENE; MUTATION; RECOMMENDATIONS; PHENOTYPE;
STANDARDS; TESTS; SPG7
AB Evaluating the pathogenicity of a variant is challenging given the plethora of types of genetic evidence that laboratories consider. Deciding how to weigh each type of evidence is difficult, and standards have been needed. In 2015, the American College of Medical Genetics and Genomics (ACMG) and the Association for Molecular Pathology (AMP) published guidelines for the assessment of variants in genes associated with Mendelian diseases. Nine molecular diagnostic laboratories involved in the Clinical Sequencing Exploratory Research (CSER) consortium piloted these guidelines on 99 variants spanning all categories (pathogenic, likely pathogenic, uncertain significance, likely benign, and benign). Nine variants were distributed to all laboratories, and the remaining 90 were evaluated by three laboratories. The laboratories classified each variant by using both the laboratory's own method and the ACMG-AMP criteria. The agreement between the two methods used within laboratories was high (K-alpha = 0.91) with 79% concordance. However, there was only 34% concordance for either classification system across laboratories. After consensus discussions and detailed review of the ACMG=AMP criteria, concordance increased to 71%. Causes of initial discordance in ACMG-AMP classifications were identified, and recommendations on clarification and increased specification of the ACMG-AMP criteria were made. In summary, although an initial pilot of the ACMG-AMP guidelines did not lead to increased concordance in variant interpretation, comparing variant interpretations to identify differences and having a common framework to facilitate resolution of those differences were beneficial for improving agreement, allowing iterative movement toward increased reporting consistency for variants in genes associated with monogenic disease.
C1 [Amendola, Laura M.; Jarvik, Gail P.; Hart, Ragan; Ou, Jeffrey; Salama, Joseph] Univ Washington, Dept Med, Div Med Genet, Seattle, WA 98195 USA.
[Leo, Michael C.] Kaiser Permanente, Ctr Hlth Res, Portland, OR 97227 USA.
[McLaughlin, Heather M.; Green, Robert C.; Lebo, Matthew S.; Rehm, Heidi L.] Partners HealthCare Personalized Med, Mol Med Lab, Cambridge, MA 02139 USA.
[Akkari, Yassmine; Pak, Christine M.; Punj, Sumit; Richards, Carolyn Sue] Oregon Hlth & Sci Univ, Dept Mol & Med Genet, Portland, OR 97239 USA.
[Amaral, Michelle D.; Bowling, Kevin M.; Cooper, Greg M.] HudsonAlpha Inst Biotechnol, Huntsville, AL 35806 USA.
[Berg, Jonathan S.; Strande, Natasha T.] Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA.
[Biswas, Sawona; Conlin, Laura K.] Childrens Hosp Philadelphia, Dept Pediat, Div Human Genet, Philadelphia, PA 19104 USA.
[Dorschner, Michael O.] Univ Washington, Dept Pathol, Ctr Precis Diagnost, Seattle, WA 98195 USA.
[Dulik, Matthew C.] Childrens Hosp Philadelphia, Dept Pathol & LaboratoryMedicine, Philadelphia, PA 19104 USA.
[Ghazani, Arezou A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA.
[Ghosh, Rajarshi; Milosavljevic, Aleksandar; Patel, Ronak Y.; Yang, Yaping; Plon, Sharon E.] Baylor Coll Med, Houston, TX 77030 USA.
[Green, Robert C.; Lebo, Matthew S.; Rehm, Heidi L.] Brigham & Womens Hosp, Cambridge, MA 02115 USA.
[Green, Robert C.; Lebo, Matthew S.; Rehm, Heidi L.] Harvard Univ, Sch Med, Cambridge, MA 02115 USA.
[Horton, Carrie] Ambry Genet, Clin Diagnost, Aliso Viejo, CA 92656 USA.
[Johnston, Jennifer J.; Biesecker, Leslie G.] NHGRI, Intramural Res Program, NIH, Bethesda, MD 20892 USA.
[Green, Robert C.; Rehm, Heidi L.] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.
RP Jarvik, GP (reprint author), Univ Washington, Dept Med, Div Med Genet, Seattle, WA 98195 USA.; Rehm, HL (reprint author), Partners HealthCare Personalized Med, Mol Med Lab, Cambridge, MA 02139 USA.; Rehm, HL (reprint author), Brigham & Womens Hosp, Cambridge, MA 02115 USA.; Rehm, HL (reprint author), Harvard Univ, Sch Med, Cambridge, MA 02115 USA.; Rehm, HL (reprint author), Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.
EM pair@u.washington.edu; hrehm@partners.org
OI Strande, Natasha/0000-0001-5148-9772; Lebo, Matthew/0000-0002-9733-5207
FU National Human Genome Research Institute (NHGRI); National Cancer
Institute [UO1HG0006546, U01HG006485, U01HG006500, U01HG006492,
UM1HG007301, UM1HG007292, UM1HG006508, U01HG006487, U01HG006507,
U01HG007307, U41HG006834]; NIH NHGRI; The National Cancer Institute
[R21HG006596, P50HG007257, R01HG006600, R01HG004500, R01CA154517,
R01HG006618, R21HG006594-01, R01HG006615-01, R21HG006612,
5R21HG006613-02]
FX This work was funded by the National Human Genome Research Institute
(NHGRI) and National Cancer Institute (UO1HG0006546, U01HG006485,
U01HG006500, U01HG006492, UM1HG007301, UM1HG007292, UM1HG006508,
U01HG006487, U01HG006507, U01HG007307, U41HG006834, R21HG006596,
R01HG006600, P50HG007257, R01HG006600, R01HG004500, R01CA154517,
R01HG006618, R21HG006594-01, R01HG006615-01, R21HG006612, and
5R21HG006613-02) and additional support from the participating
laboratories. This research was supported in part by the Intramural
Research Program of the NIH NHGRI. We thank the following individuals
for contributing to variant assessment at the sites: Hana Zouk, PhD;
Steven M. Harrison, PhD; Jillian G. Buchan, PhD; Jessica Booker, PhD;
Jim Evans, MD, PhD, Kate Foreman, MS; Gloria Haskell, PhD; Kristy Lee,
MS; Julianne O'Daniel, MS; Bradford Powell, MD, PhD; Bryce Seifert, PhD;
and Karen Weck, MD.
NR 26
TC 26
Z9 26
U1 0
U2 2
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0002-9297
EI 1537-6605
J9 AM J HUM GENET
JI Am. J. Hum. Genet.
PD JUN 2
PY 2016
VL 98
IS 6
BP 1067
EP 1076
DI 10.1016/j.ajhg.2016.03.024
PG 10
WC Genetics & Heredity
SC Genetics & Heredity
GA DN7US
UT WOS:000377286000002
PM 27181684
ER
PT J
AU Sartorius, CA
Hanna, CT
Gril, B
Cruz, H
Serkova, NJ
Huber, KM
Kabos, P
Schedin, TB
Borges, VF
Steeg, PS
Cittelly, DM
AF Sartorius, C. A.
Hanna, C. T.
Gril, B.
Cruz, H.
Serkova, N. J.
Huber, K. M.
Kabos, P.
Schedin, T. B.
Borges, V. F.
Steeg, P. S.
Cittelly, D. M.
TI Estrogen promotes the brain metastatic colonization of triple negative
breast cancer cells via an astrocyte-mediated paracrine mechanism
SO ONCOGENE
LA English
DT Article
ID NERVOUS-SYSTEM METASTASES; RECEPTOR-ALPHA; AROMATASE EXPRESSION;
PROGNOSTIC-FACTORS; TUMOR-GROWTH; IN-VITRO; ESTRADIOL; SURVIVAL; S100A4;
BETA
AB Brain metastases (BM) are a devastating consequence of breast cancer. BM occur more frequently in patients with estrogen receptor-negative (ER-) breast cancer subtypes; HER2 overexpressing (HER2+) tumors and triple-negative (TN) (ER-, progesterone receptor-negative (PR-) and normal HER2) tumors. Young age is an independent risk factor for the development of BM, thus we speculated that higher circulating estrogens in young, pre-menopausal women could exert paracrine effects through the highly estrogen-responsive brain microenvironment. Using a TN experimental metastases model, we demonstrate that ovariectomy decreased the frequency of magnetic resonance imaging-detectable lesions by 56% as compared with estrogen supplementation, and that the combination of ovariectomy and letrozole further reduced the frequency of large lesions to 14.4% of the estrogen control. Human BM expressed 4.2-48.4% ER+ stromal area, particularly ER+ astrocytes. In vitro, E2-treated astrocytes increased proliferation, migration and invasion of 231BR-EGFP cells in an ER-dependent manner. E2 upregulated epidermal growth factor receptor (EGFR) ligands Egf, Ereg and Tgfa mRNA and protein levels in astrocytes, and activated EGFR in brain metastatic cells. Co-culture of 231BR-EGFP cells with E2-treated astrocytes led to the upregulation of the metastatic mediator S100 Calcium-binding protein A4 (S100A4) (1.78-fold, P < 0.05). Exogenous EGF increased S100A4 mRNA levels in 231BR-EGFP cells (1.40 +/- 0.02-fold, P < 0.01 compared with vehicle control) and an EGFR/HER2 inhibitor blocked this effect, suggesting that S100A4 is a downstream effector of EGFR activation. Short hairpin RNA-mediated S100A4 silencing in 231BR-EGFP cells decreased their migration and invasion in response to E2-CM, abolished their increased proliferation in co-cultures with E2-treated astrocytes and decreased brain metastatic colonization. Thus, S100A4 is one effector of the paracrine action of E2 in brain metastatic cells. These studies provide a novel mechanism by which estrogens, acting through ER+ astrocytes in the brain microenvironment, can promote BM of TN breast cancers, and suggests existing endocrine agents may provide some clinical benefit towards reducing and managing BM.
C1 [Sartorius, C. A.; Hanna, C. T.; Cruz, H.; Cittelly, D. M.] Univ Colorado Denver, Dept Pathol, Anschutz Med Campus, Aurora, CO 80045 USA.
[Gril, B.; Steeg, P. S.] NCI, Womens Malignancies Branch, Bethesda, MD 20892 USA.
[Serkova, N. J.; Huber, K. M.] Univ Colorado Denver, Dept Anesthesiol, Anschutz Med, Aurora, CO 80045 USA.
[Kabos, P.; Schedin, T. B.; Borges, V. F.] Univ Colorado Denver, Div Med Oncol, Dept Med, Anschutz Med Campus, Aurora, CO 80045 USA.
RP Cittelly, DM (reprint author), Univ Colorado Denver, Dept Pathol, Anschutz Med Campus,12801 E 17th Ave MS8104, Aurora, CO 80045 USA.
EM Diana.Cittelly@ucdenver.edu
FU NCI [P30CA046934, K22CA181250]; CTSA Center grant [UL1TR001082]; DOD
BCRP [W81XWH-11-1-0101]; ACS IRG [57-001-53]; NIH [R01 CA140985]
FX We thank the University of Colorado Cancer Center Animal Imaging Shared
Resources, Tissue Culture Core, Cytometry and Cell Sorting Shared
Resource and Functional Genomics Facility supported by NCI P30CA046934
and CTSA UL1TR001082 Center grants. Susan Edgerton provided
de-identified tissue. This work was supported by DOD BCRP
W81XWH-11-1-0101 (DMC), ACS IRG # 57-001-53 (DMC) and NCI K22CA181250
(DMC). CAS was supported by NIH R01 CA140985.
NR 54
TC 3
Z9 3
U1 4
U2 10
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0950-9232
EI 1476-5594
J9 ONCOGENE
JI Oncogene
PD JUN 2
PY 2016
VL 35
IS 22
BP 2881
EP 2892
DI 10.1038/onc.2015.353
PG 12
WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
GA DO0MT
UT WOS:000377473700008
PM 26411365
ER
PT J
AU Tweedie, D
Fukui, K
Li, YZ
Yu, QS
Barak, S
Tamargo, IA
Rubovitch, V
Holloway, HW
Lehrmann, E
Wood, WH
Zhang, YQ
Becker, KG
Perez, E
Van Praag, H
Luo, Y
Hoffer, BJ
Becker, RE
Pick, CG
Greig, NH
AF Tweedie, David
Fukui, Koji
Li, Yazhou
Yu, Qian-sheng
Barak, Shani
Tamargo, Ian A.
Rubovitch, Vardit
Holloway, Harold W.
Lehrmann, Elin
Wood, William H., III
Zhang, Yongqing
Becker, Kevin G.
Perez, Evelyn
Van Praag, Henriette
Luo, Yu
Hoffer, Barry J.
Becker, Robert E.
Pick, Chaim G.
Greig, Nigel H.
TI Cognitive Impairments Induced by Concussive Mild Traumatic Brain Injury
in Mouse Are Ameliorated by Treatment with Phenserine via Multiple
Non-Cholinergic and Cholinergic Mechanisms
SO PLOS ONE
LA English
DT Article
ID OBJECT RECOGNITION MEMORY; FLUID-PERCUSSION INJURY; CORTICAL IMPACT
INJURY; ALZHEIMERS-DISEASE; HEAD-INJURY; OXIDATIVE STRESS;
CHOLINESTERASE-INHIBITORS; ACETYLCHOLINESTERASE INHIBITION; PARKINSON
DISEASE; RECEPTOR-BINDING
AB Traumatic brain injury (TBI), often caused by a concussive impact to the head, affects an estimated 1.7 million Americans annually. With no approved drugs, its pharmacological treatment represents a significant and currently unmet medical need. In our prior development of the anti-cholinesterase compound phenserine for the treatment of neurodegenerative disorders, we recognized that it also possesses non-cholinergic actions with clinical potential. Here, we demonstrate neuroprotective actions of phenserine in neuronal cultures challenged with oxidative stress and glutamate excitotoxicity, two insults of relevance to TBI. These actions translated into amelioration of spatial and visual memory impairments in a mouse model of closed head mild TBI (mTBI) two days following cessation of clinically translatable dosing with phenserine (2.5 and 5.0 mg/kg BID x 5 days initiated post mTBI) in the absence of anti-cholinesterase activity. mTBI elevated levels of thiobarbituric acid reactive substances (TBARS), a marker of oxidative stress. Phenserine counteracted this by augmenting homeostatic mechanisms to mitigate oxidative stress, including superoxide dismutase [SOD] 1 and 2, and glutathione peroxidase [GPx], the activity and protein levels of which were measured by specific assays. Microarray analysis of hippocampal gene expression established that large numbers of genes were exclusively regulated by each individual treatment with a substantial number of them co-regulated between groups. Molecular pathways associated with lipid peroxidation were found to be regulated by mTBI, and treatment of mTBI animals with phenserine effectively reversed injury-induced regulations in the 'Blalock Alzheimer's Disease Up' pathway. Together these data suggest that multiple phenserine-associated actions underpin this compound's ability to ameliorate cognitive deficits caused by mTBI, and support the further evaluation of the compound as a therapeutic for TBI.
C1 [Tweedie, David; Fukui, Koji; Li, Yazhou; Yu, Qian-sheng; Tamargo, Ian A.; Holloway, Harold W.; Becker, Robert E.; Greig, Nigel H.] NIA, Translat Gerontol Branch, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
[Fukui, Koji] Shibaura Inst Technol, Div Biosci & Engn, Saitama 3378570, Japan.
[Barak, Shani; Rubovitch, Vardit; Pick, Chaim G.] Tel Aviv Univ, Sackler Sch Med, Dept Anat & Anthropol, IL-69978 Tel Aviv, Israel.
[Lehrmann, Elin; Wood, William H., III; Zhang, Yongqing; Becker, Kevin G.] NIA, Lab Genet & Genom, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
[Perez, Evelyn] NIA, Lab Behav Neurosci, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
[Van Praag, Henriette] NIA, Neurosci Lab, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
[Luo, Yu; Hoffer, Barry J.] Case Western Reserve Univ, Sch Med, Dept Neurosurg, Cleveland, OH USA.
[Becker, Robert E.] 7123 Pinebrook Rd, Park City, UT 84098 USA.
[Pick, Chaim G.] Tel Aviv Univ, Sagol Sch Neurosci, IL-69978 Tel Aviv, Israel.
RP Greig, NH (reprint author), NIA, Translat Gerontol Branch, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
EM greign@mail.nih.gov
RI van Praag, Henriette/F-3939-2015
OI van Praag, Henriette/0000-0002-5727-434X
FU Intramural Research Program of the National Institute on Aging, National
Institutes of Health; Ari and Regine Aprijaskis Fund, at Tel-Aviv
University; Israel Science Foundation [108/09]
FX This research was supported in part by (i) the Intramural Research
Program of the National Institute on Aging, National Institutes of
Health, (ii) the Ari and Regine Aprijaskis Fund, at Tel-Aviv University,
and (iii) a grant from the Israel Science Foundation, grant number
108/09. The funders had no role in study design, data collection and
analysis, decision to publish, or preparation of the manuscript.; This
research was supported in part by (i) the Intramural Research Program of
the National Institute on Aging, National Institutes of Health, (ii) the
Ari and Regine Aprijaskis Fund, at Tel-Aviv University, and (iii) a
grant from the Israel Science Foundation, grant number 108/09.
NR 127
TC 0
Z9 0
U1 3
U2 4
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUN 2
PY 2016
VL 11
IS 6
AR e0156493
DI 10.1371/journal.pone.0156493
PG 26
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DN6XB
UT WOS:000377218700033
PM 27254111
ER
PT J
AU Sutherland, MT
Riedel, MC
Flannery, JS
Yanes, JA
Fox, PT
Stein, EA
Laird, AR
AF Sutherland, Matthew T.
Riedel, Michael C.
Flannery, Jessica S.
Yanes, Julio A.
Fox, Peter T.
Stein, Elliot A.
Laird, Angela R.
TI Chronic cigarette smoking is linked with structural alterations in brain
regions showing acute nicotinic drug-induced functional modulations
SO BEHAVIORAL AND BRAIN FUNCTIONS
LA English
DT Article
DE Cigarettes; Nicotine; Addiction; Gray matter; Morphometry; Insula;
Mediodorsal thalamus; Ventromedial prefrontal cortex; Cerebellum
ID GRAY-MATTER VOLUME; INTRINSIC CONNECTIVITY NETWORKS; VOXEL-BASED
MORPHOMETRY; YOUNG-ADULT SMOKERS; NEUROIMAGING DATA; DECISION-MAKING;
METAANALYTIC CONNECTIVITY; ACETYLCHOLINE-RECEPTORS; COGNITIVE-PROCESSES;
CORTICAL THICKNESS
AB Background: Whereas acute nicotine administration alters brain function which may, in turn, contribute to enhanced attention and performance, chronic cigarette smoking is linked with regional brain atrophy and poorer cognition. However, results from structural magnetic resonance imaging (MRI) studies comparing smokers versus nonsmokers have been inconsistent and measures of gray matter possess limited ability to inform functional relations or behavioral implications. The purpose of this study was to address these interpretational challenges through metaanalytic techniques in the service of clarifying the impact of chronic smoking on gray matter integrity and more fully contextualizing such structural alterations.
Methods: We first conducted a coordinate-based meta-analysis of structural MRI studies to identify consistent structural alterations associated with chronic smoking. Subsequently, we conducted two additional meta-analytic assessments to enhance insight into potential functional and behavioral relations. Specifically, we performed a multimodal meta-analytic assessment to test the structural-functional hypothesis that smoking-related structural alterations overlapped those same regions showing acute nicotinic drug-induced functional modulations. Finally, we employed database driven tools to identify pairs of structurally impacted regions that were also functionally related via meta-analytic connectivity modeling, and then delineated behavioral phenomena associated with such functional interactions via behavioral decoding.
Results: Across studies, smoking was associated with convergent structural decreases in the left insula, right cerebellum, parahippocampus, multiple prefrontal cortex (PFC) regions, and the thalamus. Indicating a structural-functional relation, we observed that smoking-related gray matter decreases overlapped with the acute functional effects of nicotinic agonist administration in the left insula, ventromedial PFC, and mediodorsal thalamus. Suggesting structural-behavioral implications, we observed that the left insula's task-based, functional interactions with multiple other structurally impacted regions were linked with pain perception, the right cerebellum's interactions with other regions were associated with overt body movements, interactions between the parahippocampus and thalamus were linked with memory processes, and interactions between medial PFC regions were associated with face processing.
Conclusions: Collectively, these findings emphasize brain regions (e.g., ventromedial PFC, insula, thalamus) critically linked with cigarette smoking, suggest neuroimaging paradigms warranting additional consideration among smokers (e.g., pain processing), and highlight regions in need of further elucidation in addiction (e.g., cerebellum).
C1 [Sutherland, Matthew T.; Riedel, Michael C.; Flannery, Jessica S.] Florida Int Univ, Dept Psychol, AHC 4,RM 312,11200 SW 8th St, Miami, FL 33199 USA.
[Riedel, Michael C.; Laird, Angela R.] Florida Int Univ, Dept Phys, Miami, FL 33199 USA.
[Yanes, Julio A.] Auburn Univ, Dept Psychol, Auburn, AL 36849 USA.
[Fox, Peter T.] Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Inst, San Antonio, TX 78229 USA.
[Fox, Peter T.] South Texas Vet Hlth Care Syst, San Antonio, TX USA.
[Fox, Peter T.] Univ Hong Kong, State Key Lab Brain & Cognit Sci, Hong Kong, Hong Kong, Peoples R China.
[Stein, Elliot A.] NIDA, Neuroimaging Res Branch, Intramural Res Program, NIH DHHS, Baltimore, MD USA.
RP Sutherland, MT (reprint author), Florida Int Univ, Dept Psychol, AHC 4,RM 312,11200 SW 8th St, Miami, FL 33199 USA.
EM masuther@fiu.edu
OI Sutherland, Matthew/0000-0002-6091-4037
FU National Institute on Drug Abuse of the NIH [K01-DA037819]; National
Institute of Mental Health of the NIH [R01-MH074457, R56-MH097870];
Intramural Research Program of the National Institute on Drug Abuse
FX This work was supported by the National Institute on Drug Abuse
(K01-DA037819, MTS) and the National Institute of Mental Health
(R01-MH074457 and R56-MH097870, ARL and PTF) of the NIH. EAS is
supported by the Intramural Research Program of the National Institute
on Drug Abuse. The content is solely the responsibility of the authors
and does not necessarily represent the official views of the NIH.
NR 112
TC 1
Z9 1
U1 3
U2 8
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1744-9081
J9 BEHAV BRAIN FUNCT
JI Behav. Brain Funct.
PD JUN 2
PY 2016
VL 12
AR 16
DI 10.1186/s12993-016-0100-5
PG 15
WC Behavioral Sciences; Neurosciences
SC Behavioral Sciences; Neurosciences & Neurology
GA DN4TV
UT WOS:000377061000001
PM 27251183
ER
PT J
AU Kubben, N
Zhang, WQ
Wang, LX
Voss, TC
Yang, JP
Qu, J
Liu, GH
Misteli, T
AF Kubben, Nard
Zhang, Weiqi
Wang, Lixia
Voss, Ty C.
Yang, Jiping
Qu, Jing
Liu, Guang-Hui
Misteli, Tom
TI Repression of the Antioxidant NRF2 Pathway in Premature Aging
SO CELL
LA English
DT Article
ID GILFORD-PROGERIA-SYNDROME; MESENCHYMAL STEM-CELLS; DNA-DAMAGE RESPONSES;
OXIDATIVE STRESS; INFLAMMATORY RESPONSE; DEFECTIVE MATURATION;
TRANSCRIPTION FACTOR; ROS GENERATION; LAMIN; ACTIVATION
AB Hutchinson-Gilford progeria syndrome (HGPS) is a rare, invariably fatal premature aging disorder. The disease is caused by constitutive production of progerin, a mutant form of the nuclear architectural protein lamin A, leading, through unknown mechanisms, to diverse morphological, epigenetic, and genomic damage and to mesenchymal stem cell (MSC) attrition in vivo. Using a high-throughput siRNA screen, we identify the NRF2 antioxidant pathway as a driver mechanism in HGPS. Progerin sequesters NRF2 and thereby causes its subnuclear mislocalization, resulting in impaired NRF2 transcriptional activity and consequently increased chronic oxidative stress. Suppressed NRF2 activity or increased oxidative stress is sufficient to recapitulate HGPS aging defects, whereas reactivation of NRF2 activity in HGPS patient cells reverses progerin-associated nuclear aging defects and restores in vivo viability of MSCs in an animal model. These findings identify repression of the NRF2-mediated antioxidative response as a key contributor to the premature aging phenotype.
C1 [Kubben, Nard; Misteli, Tom] NCI, NIH, Bethesda, MD 20892 USA.
[Zhang, Weiqi; Wang, Lixia; Yang, Jiping; Liu, Guang-Hui] Chinese Acad Sci, Inst Biophys, CAS Ctr Excellence Biomacromol, Natl Lab Biomacromol, Beijing 100101, Peoples R China.
[Zhang, Weiqi; Liu, Guang-Hui] Foshan Univ, FSU CAS Innovat Inst, Foshan 528000, Guangdong, Peoples R China.
[Wang, Lixia; Qu, Jing] Chinese Acad Sci, Inst Zool, State Key Lab Stem Cell & Reprod Biol, Beijing 100101, Peoples R China.
[Voss, Ty C.] NCI, High Throughput Imaging Facil, NIH, Bethesda, MD 20892 USA.
[Liu, Guang-Hui] Beijing Inst Brain Disorders, Beijing 100069, Peoples R China.
[Wang, Lixia; Yang, Jiping; Qu, Jing; Liu, Guang-Hui] Univ Chinese Acad Sci, Beijing 100049, Peoples R China.
RP Misteli, T (reprint author), NCI, NIH, Bethesda, MD 20892 USA.; Liu, GH (reprint author), Chinese Acad Sci, Inst Biophys, CAS Ctr Excellence Biomacromol, Natl Lab Biomacromol, Beijing 100101, Peoples R China.; Liu, GH (reprint author), Foshan Univ, FSU CAS Innovat Inst, Foshan 528000, Guangdong, Peoples R China.; Liu, GH (reprint author), Beijing Inst Brain Disorders, Beijing 100069, Peoples R China.; Liu, GH (reprint author), Univ Chinese Acad Sci, Beijing 100049, Peoples R China.
EM ghliu@ibp.ac.cn; mistelit@mail.nih.gov
FU National Basic Research Program of China (973 Program) [2015CB964800,
2014CB910503]; Strategic Priority Research Program of the Chinese
Academy of Sciences [XDA01020312]; National High Technology Research and
Development Program of China [2015AA020307]; National Natural Science
Foundation of China [81330008, 31222039, 31201111, 81371342, 81300261,
81300677, 81271266, 81471414, 81422017, 81401159]; Program of Beijing
Municipal Science and Technology Commission [Z151100003915072]; Beijing
Natural Science Foundation [7141005, 5142016]; Key Research Program of
the Chinese Academy of Sciences [KJZDEW-TZ-L05]; Thousand Young Talents
program of China; Intramural Research Program of the NIH/NCI/CCR;
Progeria Research Foundation grant
FX We thank the T.M. lab members, P. Scaffidi, Y. Xiong, and J.C. Izpisua
Belmonte for sharing feedback, data, and reagents. The G.-H.L. and J.Q.
labs were supported by the National Basic Research Program of China (973
Program, 2015CB964800 and 2014CB910503), the Strategic Priority Research
Program of the Chinese Academy of Sciences (XDA01020312), the National
High Technology Research and Development Program of China
(2015AA020307), the National Natural Science Foundation of China
(81330008, 31222039, 31201111, 81371342, 81300261, 81300677, 81271266,
81471414, 81422017, and 81401159), the Program of Beijing Municipal
Science and Technology Commission (Z151100003915072), the Beijing
Natural Science Foundation (7141005 and 5142016), the Key Research
Program of the Chinese Academy of Sciences (KJZDEW-TZ-L05), and the
Thousand Young Talents program of China. The T.M. lab was supported by
the Intramural Research Program of the NIH/NCI/CCR and a Progeria
Research Foundation grant.
NR 62
TC 4
Z9 4
U1 28
U2 46
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0092-8674
EI 1097-4172
J9 CELL
JI Cell
PD JUN 2
PY 2016
VL 165
IS 6
BP 1361
EP 1374
DI 10.1016/j.cell.2016.05.017
PG 14
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA DN4NV
UT WOS:000377045400011
PM 27259148
ER
PT J
AU Lu, FL
Liu, YT
Inoue, A
Suzuki, T
Zhao, KJ
Zhang, Y
AF Lu, Falong
Liu, Yuting
Inoue, Azusa
Suzuki, Tsukasa
Zhao, Keji
Zhang, Yi
TI Establishing Chromatin Regulatory Landscape during Mouse Preimplantation
Development
SO CELL
LA English
DT Article
ID MASTER TRANSCRIPTION FACTORS; TO-ZYGOTIC TRANSITION; GENE-EXPRESSION;
HYPERSENSITIVE SITES; DNA LANDSCAPES; CELL FATE; GENOME; ACCESSIBILITY;
EMBRYO; DYNAMICS
AB How the chromatin regulatory landscape in the inner cell mass cells is established from differentially packaged sperm and egg genomes during preimplantation development is unknown. Here, we develop a low-input DNase I sequencing (liDNase-seq) method that allows us to generate maps of DNase I-hypersensitive site (DHS) of mouse preimplantation embryos from 1-cell to morula stage. The DHS landscape is progressively established with a drastic increase at the 8-cell stage. Paternal chromatin accessibility is quickly reprogrammed after fertilization to the level similar to maternal chromatin, while imprinted genes exhibit allelic accessibility bias. We demonstrate that transcription factor Nfya contributes to zygotic genome activation and DHS formation at the 2-cell stage and that Oct4 contributes to the DHSs gained at the 8-cell stage. Our study reveals the dynamic chromatin regulatory landscape during early development and identifies key transcription factors important for DHS establishment in mammalian embryos.
C1 [Lu, Falong; Liu, Yuting; Inoue, Azusa; Suzuki, Tsukasa; Zhang, Yi] Boston Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA.
[Lu, Falong; Liu, Yuting; Inoue, Azusa; Suzuki, Tsukasa; Zhang, Yi] Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA.
[Lu, Falong; Liu, Yuting; Inoue, Azusa; Suzuki, Tsukasa; Zhang, Yi] Boston Childrens Hosp, Div Hematol Oncol, Dept Pediat, Boston, MA 02115 USA.
[Zhang, Yi] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
[Zhang, Yi] Harvard Stem Cell Inst, WAB 149G,200 Longwood Ave, Boston, MA 02115 USA.
[Zhao, Keji] NHLBI, Syst Biol Ctr, Div Intramural Res, NIH, Bldg 10, Bethesda, MD 20892 USA.
RP Zhang, Y (reprint author), Boston Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA.; Zhang, Y (reprint author), Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA.; Zhang, Y (reprint author), Boston Childrens Hosp, Div Hematol Oncol, Dept Pediat, Boston, MA 02115 USA.; Zhang, Y (reprint author), Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.; Zhang, Y (reprint author), Harvard Stem Cell Inst, WAB 149G,200 Longwood Ave, Boston, MA 02115 USA.
EM yzhang@genetics.med.harvard.edu
RI Lu, Falong/Q-3013-2016
FU HHMI; Charles A. King Trust
FX We thank Dr. Shinpei Yamaguchi for helpful discussion and Dr. Luis
Tuesta for critical reading of the manuscript. This project is supported
by HHMI. F.L. is supported by a Charles A. King Trust Postdoctoral
Research Fellowship. Y.Z. is an investigator of the Howard Hughes
Medical Institute.
NR 41
TC 9
Z9 9
U1 14
U2 25
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0092-8674
EI 1097-4172
J9 CELL
JI Cell
PD JUN 2
PY 2016
VL 165
IS 6
BP 1375
EP 1388
DI 10.1016/j.cell.2016.05.050
PG 14
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA DN4NV
UT WOS:000377045400012
PM 27259149
ER
PT J
AU Haque, N
Hogg, JR
AF Haque, Nazmul
Hogg, J. Robert
TI Easier, Better, Faster, Stronger: Improved Methods for RNA-Protein
Interaction Studies
SO MOLECULAR CELL
LA English
DT Editorial Material
ID GENERATION; CLIP
AB The RNA field has been revolutionized by methods that allow genome-scale identification of RNA-protein interaction sites. Two reports now introduce more efficient approaches, opening the technology to wider adoption (Van Nostrand et al., 2016; Zarnegar et al., 2016).
C1 [Haque, Nazmul; Hogg, J. Robert] NHLBI, Biochem & Biophys Ctr, NIH, Bldg 10, Bethesda, MD 20892 USA.
RP Hogg, JR (reprint author), NHLBI, Biochem & Biophys Ctr, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM j.hogg@nih.gov
OI Hogg, J. Robert/0000-0001-5729-5135
NR 8
TC 0
Z9 0
U1 2
U2 5
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1097-2765
EI 1097-4164
J9 MOL CELL
JI Mol. Cell
PD JUN 2
PY 2016
VL 62
IS 5
BP 650
EP 651
DI 10.1016/j.molcel.2016.05.019
PG 2
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA DN4PK
UT WOS:000377049500002
PM 27259196
ER
PT J
AU Thompson, PJ
Macfarlan, TS
Lorincz, MC
AF Thompson, Peter J.
Macfarlan, Todd S.
Lorincz, Matthew C.
TI Long Terminal Repeats: From Parasitic Elements to Building Blocks of the
Transcriptional Regulatory Repertoire
SO MOLECULAR CELL
LA English
DT Review
ID EMBRYONIC STEM-CELLS; HUMAN ENDOGENOUS RETROVIRUSES; DNA METHYLATION
LANDSCAPE; MOUSE ES CELLS; TRANSPOSABLE ELEMENTS; NONCODING RNA; HUMAN
GENOME; GENE-EXPRESSION; PREIMPLANTATION EMBRYOS; CHIMERIC TRANSCRIPTS
AB The life cycle of endogenous retroviruses (ERVs), also called long terminal repeat (LTR) retrotransposons, begins with transcription by RNA polymerase II followed by reverse transcription and re-integration into the host genome. While most ERVs are relics of ancient integration events, "young'' proviruses competent for retro-transposition-found in many mammals, but not humans-represent an ongoing threat to host fitness. As a consequence, several restriction pathways have evolved to suppress their activity at both transcriptional and post-transcriptional stages of the viral life cycle. Nevertheless, accumulating evidence has revealed that LTR sequences derived from distantly related ERVs have been exapted as regulatory sequences for many host genes in a wide range of cell types throughout mammalian evolution. Here, we focus on emerging themes from recent studies cataloging the diversity of ERV LTRs acting as important transcriptional regulatory elements in mammals and explore the molecular features that likely account for LTR exaptation in developmental and tissue-specific gene regulation.
C1 [Thompson, Peter J.; Lorincz, Matthew C.] Univ British Columbia, Inst Life Sci, Dept Med Genet, Vancouver, BC V6T 1Z3, Canada.
[Macfarlan, Todd S.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD 20892 USA.
[Thompson, Peter J.] Univ Calif San Francisco, Dept Med, Ctr Diabet, San Francisco, CA 94143 USA.
RP Lorincz, MC (reprint author), Univ British Columbia, Inst Life Sci, Dept Med Genet, Vancouver, BC V6T 1Z3, Canada.; Macfarlan, TS (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD 20892 USA.
EM todd.macfarlan@nih.gov; mlorincz@mail.ubc.ca
FU Canadian Institutes of Health Research [MOP-133417]; NIH [1ZIAHD008933]
FX We wish to thank Dixie Mager and Cedric Feschotte for critical reading
of the manuscript. This work was supported by Canadian Institutes of
Health Research Grant MOP-133417 (M.C.L.) and NIH grant 1ZIAHD008933
(T.S.M.).
NR 112
TC 6
Z9 6
U1 3
U2 9
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1097-2765
EI 1097-4164
J9 MOL CELL
JI Mol. Cell
PD JUN 2
PY 2016
VL 62
IS 5
BP 766
EP 776
DI 10.1016/j.molcel.2016.03.029
PG 11
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA DN4PK
UT WOS:000377049500013
PM 27259207
ER
PT J
AU Mertins, P
Mani, DR
Ruggles, KV
Gillette, MA
Clauser, KR
Wang, P
Wang, XL
Qiao, JW
Cao, S
Petralia, F
Kawaler, E
Mundt, F
Krug, K
Tu, ZD
Lei, JT
Gatza, ML
Wilkerson, M
Perou, CM
Yellapantula, V
Huang, KL
Lin, CW
McLellan, MD
Yan, P
Davies, SR
Townsend, RR
Skates, SJ
Wang, J
Zhang, B
Kinsinger, CR
Mesri, M
Rodriguez, H
Ding, L
Paulovich, AG
Fenyo, D
Ellis, MJ
Carr, SA
AF Mertins, Philipp
Mani, D. R.
Ruggles, Kelly V.
Gillette, Michael A.
Clauser, Karl R.
Wang, Pei
Wang, Xianlong
Qiao, Jana W.
Cao, Song
Petralia, Francesca
Kawaler, Emily
Mundt, Filip
Krug, Karsten
Tu, Zhidong
Lei, Jonathan T.
Gatza, Michael L.
Wilkerson, Matthew
Perou, Charles M.
Yellapantula, Venkata
Huang, Kuan-lin
Lin, Chenwei
McLellan, Michael D.
Yan, Ping
Davies, Sherri R.
Townsend, R. Reid
Skates, Steven J.
Wang, Jing
Zhang, Bing
Kinsinger, Christopher R.
Mesri, Mehdi
Rodriguez, Henry
Ding, Li
Paulovich, Amanda G.
Fenyo, David
Ellis, Matthew J.
Carr, Steven A.
CA NCI CPTAC
TI Proteogenomics connects somatic mutations to signalling in breast cancer
SO NATURE
LA English
DT Article
ID ONCOGENIC PIK3CA MUTATIONS; GENE-EXPRESSION SIGNATURES; MOLECULAR
PORTRAITS; TUMORS; RECEPTOR; PATHWAYS; PHOSPHORYLATION; HETEROGENEITY;
SUBTYPES; REVEALS
AB Somatic mutations have been extensively characterized in breast cancer, but the effects of these genetic alterations on the proteomic landscape remain poorly understood. Here we describe quantitative mass-spectrometry-based proteomic and phosphoproteomic analyses of 105 genomically annotated breast cancers, of which 77 provided high-quality data. Integrated analyses provided insights into the somatic cancer genome including the consequences of chromosomal loss, such as the 5q deletion characteristic of basal-like breast cancer. Interrogation of the 5q trans-effects against the Library of Integrated Network-based Cellular Signatures, connected loss of CETN3 and SKP1 to elevated expression of epidermal growth factor receptor (EGFR), and SKP1 loss also to increased SRC tyrosine kinase. Global proteomic data confirmed a stromal-enriched group of proteins in addition to basal and luminal clusters, and pathway analysis of the phosphoproteome identified a G-protein-coupled receptor cluster that was not readily identified at the mRNA level. In addition to ERBB2, other amplicon-associated highly phosphorylated kinases were identified, including CDK12, PAK1, PTK2, RIPK2 and TLK2. We demonstrate that proteogenomic analysis of breast cancer elucidates the functional consequences of somatic mutations, narrows candidate nominations for driver genes within large deletions and amplified regions, and identifies therapeutic targets.
C1 [Mertins, Philipp; Mani, D. R.; Gillette, Michael A.; Clauser, Karl R.; Qiao, Jana W.; Mundt, Filip; Krug, Karsten; Carr, Steven A.] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.
[Ruggles, Kelly V.; Kawaler, Emily; Fenyo, David] NYU, Langone Med Ctr, Dept Biochem & Mol Pharmacol, New York, NY 10016 USA.
[Gillette, Michael A.] Massachusetts Gen Hosp, Div Pulm & Crit Care Med, Boston, MA 02114 USA.
[Wang, Pei; Petralia, Francesca; Tu, Zhidong] Icahn Sch Med Mt Sinai, Icahn Inst Genom & Multiscale Biol, Dept Genet & Genom Sci, New York, NY 10029 USA.
[Wang, Xianlong; Lin, Chenwei; Yan, Ping; Paulovich, Amanda G.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA.
[Cao, Song; Yellapantula, Venkata; Huang, Kuan-lin; McLellan, Michael D.; Ding, Li] Washington Univ, Sch Med, Siteman Canc Ctr, Dept Med,McDonnell Genome Inst, St Louis, MO 63108 USA.
[Mundt, Filip] Karolinska Inst, Dept Oncol Pathol, S-17176 Stockholm, Sweden.
[Lei, Jonathan T.; Ellis, Matthew J.] Baylor Coll Med, Dan L Duncan Comprehens Canc Ctr, Lester & Sue Smith Breast Ctr, Houston, TX 77030 USA.
[Lei, Jonathan T.; Ellis, Matthew J.] Baylor Coll Med, Dept Med, Houston, TX 77030 USA.
[Lei, Jonathan T.; Ellis, Matthew J.] Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA.
[Gatza, Michael L.; Wilkerson, Matthew; Perou, Charles M.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Dept Genet, Chapel Hill, NC 27599 USA.
[Davies, Sherri R.; Townsend, R. Reid] Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA.
[Skates, Steven J.] Massachusetts Gen Hosp, Ctr Canc, Biostat Ctr, Boston, MA 02114 USA.
[Wang, Jing; Zhang, Bing] Vanderbilt Univ, Sch Med, Dept Biomed Informat, Nashville, TN 37232 USA.
[Wang, Jing; Zhang, Bing] Vanderbilt Univ, Sch Med, Dept Canc Biol, Nashville, TN 37232 USA.
[Kinsinger, Christopher R.; Mesri, Mehdi; Rodriguez, Henry] NCI, NIH, Bethesda, MD 20892 USA.
RP Mertins, P; Carr, SA (reprint author), Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.; Ellis, MJ (reprint author), Baylor Coll Med, Dan L Duncan Comprehens Canc Ctr, Lester & Sue Smith Breast Ctr, Houston, TX 77030 USA.; Ellis, MJ (reprint author), Baylor Coll Med, Dept Med, Houston, TX 77030 USA.; Ellis, MJ (reprint author), Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA.
EM pmertins@broadinstitute.org; Matthew.Ellis@bcm.edu; scarr@broad.mit.edu
OI Lei, Jonathan/0000-0002-0209-8051; Yellapantula,
Venkata/0000-0001-9848-3263; Fenyo, David/0000-0001-5049-3825; Ruggles,
Kelly/0000-0002-0152-0863
FU National Cancer Institute (NCI) [U24CA160034, U24CA160036, U24CA160019,
U24CA159988, U24CA160035]; CPRIT grant [RR140033]; Leidos contract
[13XS068]; National Cancer Institute (NCI) CPTAC award [U24CA160035];
NCI Cancer Center Support Grant [P30 CA91842]; NIH/NCRR Washington
University-ICTS [UL1 RR024992]; Susan G. Komen for the Cure [KG 090422];
Swedish Research Council [Dnr 2014-323]; [SUB-R01GM108711]
FX This work was supported by National Cancer Institute (NCI) CPTAC awards
U24CA160034 (Broad Institute; Fred Hutchinson Cancer Research Center),
U24CA160036 (Johns Hopkins University), U24CA160019 (Pacific Northwest
National Laboratory), U24CA159988 (Vanderbilt University), U24CA160035
(Washington University, St. Louis; University of North Carolina, Chapel
Hill). P.W. and F.P. were also supported by SUB-R01GM108711 and MJE by
CPRIT grant RR140033. M.J.E. is also a McNair Foundation Scholar. D.F.
was supported by Leidos contract 13XS068. Primary genomics data for this
study were generated by The Cancer Genome Atlas pilot project
established by the NCI and the National Human Genome Research Institute.
Resequencing of select samples conducted in this study was supported by
National Cancer Institute (NCI) CPTAC award U24CA160035. Information
about TCGA and the investigators and institutions that constitute the
TCGA research network can be found at http://cancergenome.nih.gov/. We
also acknowledge the expert assistance of J. Snider, P. Erdmann-Gilmore
and R. Connors for the preparation of the tumour tissues for
solubilization. We thank the Alvin J. Siteman Cancer Center at
Washington University School of Medicine and Barnes-Jewish Hospital in
St. Louis, for the use of the Tissue Procurement Core, which provided
accessioning, histologic processing and review for the TCGA samples
included in this study. The Siteman Cancer Center is supported in part
by an NCI Cancer Center Support Grant #P30 CA91842 (see more at
http://www.siteman.wustl.edu/ContentPage.aspx?id=243#sthash.mEU0QuXx.dpu
f). We also thank the HAMLET Core at The Washington University in St.
Louis for providing breast cancer xenograft tumors. The HAMLET Core was
supported in part by grants from NIH/NCRR Washington University-ICTS
(UL1 RR024992) and Susan G. Komen for the Cure (KG 090422). F.M. was
also supported by The Swedish Research Council (Dnr 2014-323). We also
thank A. Subramanian, C. Flynn and J. Asiedu at the Broad Institute for
their guidance and assistance in accessing LINCS to run a large number
of enrichment queries.
NR 41
TC 45
Z9 46
U1 24
U2 46
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 2
PY 2016
VL 534
IS 7605
BP 55
EP +
DI 10.1038/nature18003
PG 19
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DN3LB
UT WOS:000376962300032
PM 27251275
ER
PT J
AU Chen, II
Caprioli, A
Ohnuki, H
Kwak, H
Porcher, C
Tosato, G
AF Chen, Inn-Inn
Caprioli, Arianna
Ohnuki, Hidetaka
Kwak, Hyeongil
Porcher, Catherine
Tosato, Giovanna
TI EphrinB2 regulates the emergence of a hemogenic endothelium from the
aorta
SO SCIENTIFIC REPORTS
LA English
DT Article
ID HEMATOPOIETIC STEM-CELLS; HAEMOGENIC ENDOTHELIUM; MOUSE EMBRYO; VASCULAR
DEVELOPMENT; YOLK-SAC; DORSAL AORTA; CARDIOVASCULAR DEVELOPMENT;
DEFINITIVE HEMATOPOIESIS; FATE ACQUISITION; MAMMALIAN EMBRYO
AB Adult-type intraembryonic hematopoiesis arises from specialized endothelial cells of the dorsal aorta (DA). Despite the critical importance of this specialized endothelium for establishment of hematopoietic stem cells and adult hematopoietic lineages, the mechanisms regulating its emergence are incompletely understood. We show that EphrinB2, a principal regulator of endothelial cell function, controls the development of endothelium producing adult-type hematopoiesis. The absence of EphrinB2 impairs DA-derived hematopoiesis. Transmembrane EphrinB2 and its EphB4 receptor interact in the emerging DA, which transiently harbors EphrinB2(+) and EphB4(+) endothelial cells, thereby providing an opportunity for bi-directional cell-to-cell signaling to control the emergence of the hemogenic endothelium. Embryonic Stem (ES) cell-derived EphrinB2(+) cells are enriched with hemogenic endothelial precursors. EphrinB2 silencing impairs ES generation of hematopoietic cells but not generation of endothelial cells. The identification of EphrinB2 as an essential regulator of adult hematopoiesis provides important insight in the regulation of early hematopoietic commitment.
C1 [Chen, Inn-Inn; Caprioli, Arianna; Ohnuki, Hidetaka; Kwak, Hyeongil; Tosato, Giovanna] NCI, Lab Cellular Oncol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Chen, Inn-Inn; Porcher, Catherine] Univ Oxford, John Radcliffe Hosp, Weatherall Inst Mol Med, MRC Mol Haematol Unit, Oxford OX3 9DS, England.
[Caprioli, Arianna] Marymount Univ, 2807 N Glebe Rd, Arlington, VA 22207 USA.
RP Tosato, G (reprint author), NCI, Lab Cellular Oncol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM tosatog@mail.nih.gov
FU NCI, CCR
FX We thank Drs. S. Raft, Y. Mukouyama, S.E. Jacobsen, D. Sanchez-Martin,
O. Salvucci and Dr. D. Lowy for mice, cells and other help. The
Intramural Research Program at NCI, CCR funded this work.
NR 72
TC 1
Z9 1
U1 1
U2 5
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2045-2322
J9 SCI REP-UK
JI Sci Rep
PD JUN 2
PY 2016
VL 6
AR 27195
DI 10.1038/srep27195
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DN2BI
UT WOS:000376868700001
PM 27250641
ER
PT J
AU Innis, R
AF Innis, R.
TI POSITRON EMISSION TOMOGRAPHY OF HUMAN BRAIN CAN MONITOR
NEUROINFLAMMATION AND CAMP SIGNALING: APPLICATIONS TO ALZHEIMER'S
DISEASE AND DEPRESSION
SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
LA English
DT Meeting Abstract
C1 [Innis, R.] NIMH, Mol Imaging Branch, NIH, Bathesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0271-678X
EI 1559-7016
J9 J CEREBR BLOOD F MET
JI J. Cereb. Blood Flow Metab.
PD JUN
PY 2016
VL 36
SU 1
MA 36
BP 8
EP 9
PG 2
WC Endocrinology & Metabolism; Hematology; Neurosciences
SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology
GA EL9QY
UT WOS:000394956300015
ER
PT J
AU Santisakultarm, T
Kersbergen, C
Bandy, D
Ide, D
Choi, S
Silva, A
AF Santisakultarm, T.
Kersbergen, C.
Bandy, D.
Ide, D.
Choi, S.
Silva, A.
TI LONGITUDINAL TWO-PHOTON IMAGING OF CORTICAL MICROVESSELS AND NEURAL
ACTIVATION IN AWAKE MARMOSET MONKEYS
SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
LA English
DT Meeting Abstract
C1 [Santisakultarm, T.; Kersbergen, C.; Choi, S.; Silva, A.] NINDS, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
[Bandy, D.; Ide, D.] NIMH, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0271-678X
EI 1559-7016
J9 J CEREBR BLOOD F MET
JI J. Cereb. Blood Flow Metab.
PD JUN
PY 2016
VL 36
SU 1
MA 72
BP 25
EP 26
PG 2
WC Endocrinology & Metabolism; Hematology; Neurosciences
SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology
GA EL9QY
UT WOS:000394956300032
ER
PT J
AU Kobayashi, M
Jenko, KJ
Zoghbi, SS
Morse, C
Rallis-Frutos, D
Page, E
Lohith, TG
Ikawa, M
Jiang, T
Hong, J
Pike, VW
Innis, RB
Fujita, M
AF Kobayashi, M.
Jenko, K. J.
Zoghbi, S. S.
Morse, C.
Rallis-Frutos, D.
Page, E.
Lohith, T. G.
Ikawa, M.
Jiang, T.
Hong, J.
Pike, V. W.
Innis, R. B.
Fujita, M.
TI BLOCKADE OF TRANSLOCATOR PROTEIN (TSPO) BY XBD173 TO MEASURE SPECIFIC
BINDING OF 11C-(R)-PK 11195 IN HUMAN BRAIN: AN ONGOING STUDY
SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
LA English
DT Meeting Abstract
C1 [Kobayashi, M.; Jenko, K. J.; Zoghbi, S. S.; Morse, C.; Rallis-Frutos, D.; Page, E.; Lohith, T. G.; Ikawa, M.; Jiang, T.; Hong, J.; Pike, V. W.; Innis, R. B.; Fujita, M.] NIMH, NIH, Bethesda, MD 20892 USA.
NR 1
TC 0
Z9 0
U1 0
U2 0
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0271-678X
EI 1559-7016
J9 J CEREBR BLOOD F MET
JI J. Cereb. Blood Flow Metab.
PD JUN
PY 2016
VL 36
SU 1
MA 174
BP 91
EP 92
PG 2
WC Endocrinology & Metabolism; Hematology; Neurosciences
SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology
GA EL9QY
UT WOS:000394956300104
ER
PT J
AU Yen, C
Papoti, D
Silva, A
AF Yen, C.
Papoti, D.
Silva, A.
TI Investigating the Spatiotemporal Characteristics of the BOLD and the
Non-BOLD Response Across Cortical Layers in Awake Marmosets
SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
LA English
DT Meeting Abstract
C1 [Yen, C.; Papoti, D.; Silva, A.] NINDS, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0271-678X
EI 1559-7016
J9 J CEREBR BLOOD F MET
JI J. Cereb. Blood Flow Metab.
PD JUN
PY 2016
VL 36
SU 1
MA 214
BP 121
EP 122
PG 2
WC Endocrinology & Metabolism; Hematology; Neurosciences
SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology
GA EL9QY
UT WOS:000394956300134
ER
PT J
AU Sarles, C
Aizenstein, H
O'Hare, C
Rosso, A
Launer, L
Kritchevsky, S
Yaffe, K
Newman, A
Rosano, C
AF Sarles, C.
Aizenstein, H.
O'Hare, C.
Rosso, A.
Launer, L.
Kritchevsky, S.
Yaffe, K.
Newman, A.
Rosano, C.
TI LONG-TERM RELATIONSHIP OF SERUM BRAIN-DERIVED NEUROTROPHIC FACTOR WITH
CEREBRAL BLOOD FLOW AND COGNITION IN COGNITIVELY NORMAL ELDERS
SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
LA English
DT Meeting Abstract
C1 [Sarles, C.; Rosso, A.; Newman, A.; Rosano, C.] Univ Pittsburgh, Grad Sch Publ Hlth, Epidemiol, Pittsburgh, PA USA.
[Aizenstein, H.] Univ Pittsburgh, Psychiat, Pittsburgh, PA USA.
[O'Hare, C.] Trinity Coll Dublin, Med Gerontol, Dublin, Ireland.
[Launer, L.] NIA, Neuroepidemiol Sect, Bethesda, MD 20892 USA.
[Kritchevsky, S.] Wake Forest Sch Med, Sticht Ctr Aging, Winston Salem, NC USA.
[Yaffe, K.] Univ Calif San Francisco, Psychiat, San Francisco, CA 94143 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0271-678X
EI 1559-7016
J9 J CEREBR BLOOD F MET
JI J. Cereb. Blood Flow Metab.
PD JUN
PY 2016
VL 36
SU 1
MA 311
BP 180
EP 181
PG 2
WC Endocrinology & Metabolism; Hematology; Neurosciences
SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology
GA EL9QY
UT WOS:000394956300198
ER
PT J
AU Morton, PD
Korotcova, L
Lewis, B
Kim, D
Kumar, V
Shaikh, F
Short, E
Frank, JA
Gallo, V
Jonas, RA
Ishibashi, N
AF Morton, P. D.
Korotcova, L.
Lewis, B.
Kim, D.
Kumar, V.
Shaikh, F.
Short, E.
Frank, J. A.
Gallo, V.
Jonas, R. A.
Ishibashi, N.
TI PROLONGED HYPOXIA DEPLETES SVZ NEURAL STEM/PROGENITOR CELL POOLS
CRITICAL FOR CORTICAL DEVELOPMENT IN PIGLETS
SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
LA English
DT Meeting Abstract
C1 [Morton, P. D.; Korotcova, L.; Kim, D.; Kumar, V.; Shaikh, F.; Short, E.; Gallo, V.; Jonas, R. A.; Ishibashi, N.] Childrens Natl Med Ctr, Ctr Res Neurosci, Washington, DC 20010 USA.
[Lewis, B.; Frank, J. A.] NIH, Radiol & Imaging Sci, Bldg 10, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0271-678X
EI 1559-7016
J9 J CEREBR BLOOD F MET
JI J. Cereb. Blood Flow Metab.
PD JUN
PY 2016
VL 36
SU 1
MA 356
BP 222
EP 223
PG 2
WC Endocrinology & Metabolism; Hematology; Neurosciences
SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology
GA EL9QY
UT WOS:000394956300243
ER
PT J
AU Ikawa, M
Lohith, TG
Jenko, KJ
Shrestha, SS
Telu, S
Zoghbi, SS
Fujita, M
Pike, VW
Innis, RB
AF Ikawa, M.
Lohith, T. G.
Jenko, K. J.
Shrestha, S. S.
Telu, S.
Zoghbi, S. S.
Fujita, M.
Pike, V. W.
Innis, R. B.
TI DIFFERENTIAL IN VITRO AND IN VIVO SENSITIVITY OF [C-11]ER176 TO A SINGLE
NUCLEOTIDE POLYMORPHISM IN THE GENE FOR TRANSLOCATOR PROTEIN
SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
LA English
DT Meeting Abstract
C1 [Ikawa, M.; Lohith, T. G.; Jenko, K. J.; Shrestha, S. S.; Telu, S.; Zoghbi, S. S.; Fujita, M.; Pike, V. W.; Innis, R. B.] NIMH, Mol Imaging Branch, Bethesda, MD 20892 USA.
NR 1
TC 0
Z9 0
U1 0
U2 0
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0271-678X
EI 1559-7016
J9 J CEREBR BLOOD F MET
JI J. Cereb. Blood Flow Metab.
PD JUN
PY 2016
VL 36
SU 1
MA 413
BP 277
EP 278
PG 2
WC Endocrinology & Metabolism; Hematology; Neurosciences
SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology
GA EL9QY
UT WOS:000394956300300
ER
PT J
AU Lyoo, CH
Ikawa, M
Liow, JS
Zoghbi, SS
Morse, C
Pike, VW
Fujita, M
Innis, RB
Kreisl, WC
AF Lyoo, C. H.
Ikawa, M.
Liow, J. S.
Zoghbi, S. S.
Morse, C.
Pike, V. W.
Fujita, M.
Innis, R. B.
Kreisl, W. C.
TI RATIO METHOD FOR 11C-PBR28 IS MORE SENSITIVE FOR DETECTING THE REGIONS
WITH INCREASED TRANSLOCATOR PROTEIN BINDING IN ALZHEIMER'S DISEASE
SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
LA English
DT Meeting Abstract
C1 [Lyoo, C. H.] Yonsei Univ, Gangnam Severance Hosp, Coll Med, Neurol, Seoul, South Korea.
[Ikawa, M.; Liow, J. S.; Zoghbi, S. S.; Morse, C.; Pike, V. W.; Fujita, M.; Innis, R. B.] NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA.
[Kreisl, W. C.] Columbia Univ, Med Ctr, Taub Inst Res Alzheimers Dis & Aging Brain, New York, NY USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0271-678X
EI 1559-7016
J9 J CEREBR BLOOD F MET
JI J. Cereb. Blood Flow Metab.
PD JUN
PY 2016
VL 36
SU 1
MA 416
BP 280
EP 281
PG 2
WC Endocrinology & Metabolism; Hematology; Neurosciences
SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology
GA EL9QY
UT WOS:000394956300303
ER
PT J
AU Fujita, M
Turtzo, C
Shenouda, C
Fennell, E
Rallis-Frutos, D
Zoghbi, S
Telu, S
Hong, J
Dsurney, J
Pike, V
Innis, R
Diaz-Arrastia, R
Latour, L
AF Fujita, M.
Turtzo, C.
Shenouda, C.
Fennell, E.
Rallis-Frutos, D.
Zoghbi, S.
Telu, S.
Hong, J.
Dsurney, J.
Pike, V.
Innis, R.
Diaz-Arrastia, R.
Latour, L.
TI CHRONIC INFLAMMATION IN BRAIN PARENCHYMA DETECTED BY PET IMAGING OF
TRANSLOCATOR PROTEIN FOLLOWING A SUBDURAL HEMATOMA, ABSENT OF MRI
FINDINGS OF BRAIN INJURY
SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
LA English
DT Meeting Abstract
C1 [Fujita, M.; Fennell, E.; Rallis-Frutos, D.; Zoghbi, S.; Telu, S.; Hong, J.; Pike, V.; Innis, R.] NIMH, Mol Imaging Branch, Bethesda, MD 20892 USA.
[Turtzo, C.] NIH, Diagnost Radiol, Bldg 10, Bethesda, MD 20892 USA.
[Shenouda, C.; Dsurney, J.] NIH, Rehabil Med, Bldg 10, Bethesda, MD 20892 USA.
[Diaz-Arrastia, R.] NIMH, Ctr Neurosci & Regenerat Med, Rockville, MD 20857 USA.
[Latour, L.] NINDS, Acute Stroke Res Sect, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0271-678X
EI 1559-7016
J9 J CEREBR BLOOD F MET
JI J. Cereb. Blood Flow Metab.
PD JUN
PY 2016
VL 36
SU 1
MA 541
BP 397
EP 398
PG 2
WC Endocrinology & Metabolism; Hematology; Neurosciences
SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology
GA EL9QY
UT WOS:000394956300428
ER
PT J
AU Choi, SH
Arai, A
Silva, AC
AF Choi, S. H.
Arai, A.
Silva, A. C.
TI MONOACYLGLYCEROL LIPASE INHIBITORS REDUCE INFARCT VOLUME AND IMPROVE
FUNCTIONAL OUTCOME IN A RAT MODEL OF FOCAL CEREBRAL ISCHEMIA
SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
LA English
DT Meeting Abstract
C1 [Choi, S. H.; Silva, A. C.] NINDS, Lab Funct & Mol Imaging, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
[Arai, A.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0271-678X
EI 1559-7016
J9 J CEREBR BLOOD F MET
JI J. Cereb. Blood Flow Metab.
PD JUN
PY 2016
VL 36
SU 1
MA 766
BP 598
EP 598
PG 1
WC Endocrinology & Metabolism; Hematology; Neurosciences
SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology
GA EL9QY
UT WOS:000394956301140
ER
PT J
AU Shrestha, S
Jenko, KJ
Liow, JS
Ikawa, M
Zoghbi, SS
Innis, RB
AF Shrestha, S.
Jenko, K. J.
Liow, J. S.
Ikawa, M.
Zoghbi, S. S.
Innis, R. B.
TI CUMI-101 BINDS TO A1 ADRENOCEPTORS IN HUMAN CEREBELLUM AND IS NOT A
SUITABLE REFERENCE REGION.
SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
LA English
DT Meeting Abstract
C1 [Shrestha, S.; Jenko, K. J.; Liow, J. S.; Ikawa, M.; Zoghbi, S. S.; Innis, R. B.] NIMH, Mol Imaging Branch, Bethesda, MD 20892 USA.
NR 1
TC 0
Z9 0
U1 0
U2 0
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0271-678X
EI 1559-7016
J9 J CEREBR BLOOD F MET
JI J. Cereb. Blood Flow Metab.
PD JUN
PY 2016
VL 36
SU 1
MA 819
BP 653
EP 653
PG 1
WC Endocrinology & Metabolism; Hematology; Neurosciences
SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology
GA EL9QY
UT WOS:000394956301193
ER
PT J
AU Liow, JS
Hu, S
Hall, MD
Hines, CS
Zoghbi, SS
Shetty, HU
Pike, VW
Kreisl, WC
Herscovitch, P
Gottesman, MM
Theodore, WH
Innis, RB
AF Liow, J. S.
Hu, S.
Hall, M. D.
Hines, C. S.
Zoghbi, S. S.
Shetty, H. U.
Pike, V. W.
Kreisl, W. C.
Herscovitch, P.
Gottesman, M. M.
Theodore, W. H.
Innis, R. B.
TI [18F]FCWAY, A SEROTONIN 1A RECEPTOR RADIOLIGAND, IS A WEAK SUBSTRATE FOR
EFFLUX TRANSPORTERS AT THE HUMAN BLOOD-BRAIN BARRIER
SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
LA English
DT Meeting Abstract
C1 [Liow, J. S.; Zoghbi, S. S.; Shetty, H. U.; Pike, V. W.; Innis, R. B.] NIMH, Mol Imaging Branch, Bethesda, MD 20892 USA.
[Hu, S.] Cent S Univ, Nucl Med, XiangYa Hosp, Changsha, Hunan, Peoples R China.
[Hall, M. D.; Gottesman, M. M.] NCI, Cell Biol Lab, Bldg 37, Bethesda, MD 20892 USA.
[Hines, C. S.] Univ Texas Hlth Sci Ctr San Antonio, Psychiat, San Antonio, TX 78229 USA.
[Kreisl, W. C.] Columbia Univ, Neurol, New York, NY USA.
[Herscovitch, P.] NIH, Clin Ctr PET, Bldg 10, Bethesda, MD 20892 USA.
[Theodore, W. H.] NINDS, Clin Epilepsy Sect, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
NR 1
TC 0
Z9 0
U1 0
U2 0
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0271-678X
EI 1559-7016
J9 J CEREBR BLOOD F MET
JI J. Cereb. Blood Flow Metab.
PD JUN
PY 2016
VL 36
SU 1
MA 864
BP 692
EP 693
PG 2
WC Endocrinology & Metabolism; Hematology; Neurosciences
SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology
GA EL9QY
UT WOS:000394956301238
ER
PT J
AU Wang, J
Wang, J
Yang, L
Greig, N
AF Wang, J.
Wang, J.
Yang, L.
Greig, N.
TI NEUROPROTECTIVE EFFECTS AND MECHANISM OF POMALIDOMIDE AGAINST TRAUMATIC
BRAIN INJURY
SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
LA English
DT Meeting Abstract
C1 [Wang, J.; Wang, J.; Yang, L.] Taipei Med Univ, Grad Inst Med Sci, Taipei, Taiwan.
[Greig, N.] NIA, Drug Design & Dev Sect, Baltimore, MD 21224 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0271-678X
EI 1559-7016
J9 J CEREBR BLOOD F MET
JI J. Cereb. Blood Flow Metab.
PD JUN
PY 2016
VL 36
SU 1
MA 1018
BP 813
EP 813
PG 1
WC Endocrinology & Metabolism; Hematology; Neurosciences
SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology
GA EL9QY
UT WOS:000394956301392
ER
PT J
AU Yoshida, S
Martines, J
Lawn, JE
Wall, S
Souza, JP
Rudan, I
Cousens, S
Aaby, P
Adam, I
Adhikari, RK
Ambalavanan, N
El Arifeen, S
Aryal, DR
Asiruddin, SK
Baqui, A
Barros, AJD
Benn, CS
Bhandari, V
Bhatnagar, S
Bhattacharya, S
Bhutta, ZA
Black, RE
Blencowe, H
Bose, C
Brown, J
Buhrer, C
Carlo, W
Cecatti, JG
Cheung, PY
Clark, R
Colbourn, T
Conde-Agudelo, A
Corbett, E
Czeizel, AE
Das, A
Day, LT
Deal, C
Deorari, A
Dilmen, U
English, M
Engmann, C
Esamai, F
Fall, C
Ferriero, DM
Gisore, P
Hazir, T
Higgins, RD
Homer, CSE
Hoque, DE
Irgens, L
Islam, MT
de Graft-Johnson, J
Joshua, MA
Keenan, W
Khatoon, S
Kieler, H
Kramer, MS
Lackritz, EM
Lavender, T
Lawintono, L
Luhanga, R
Marsh, D
McMillan, D
McNamara, PJ
Mol, BJ
Molyneux, E
Mukasa, GK
Mutabazi, M
Nacul, LC
Nakakeeto, M
Narayanan, I
Olusanya, B
Osrin, D
Paul, V
Poets, C
Reddy, UM
Santosham, M
Sayed, R
Schlabritz-Loutsevitch, NE
Singhal, N
Smith, MA
Smith, PG
Soofi, S
Spong, CY
Sultana, S
Tshefu, A
van Bel, F
Gray, LV
Waiswa, P
Wang, W
Williams, SLA
Wright, L
Zaidi, A
Zhang, YF
Zhong, N
Zuniga, I
Bahl, R
AF Yoshida, Sachiyo
Martines, Jose
Lawn, Joy E.
Wall, Stephen
Souza, Joao Paulo
Rudan, Igor
Cousens, Simon
Aaby, Peter
Adam, Ishag
Adhikari, Ramesh Kant
Ambalavanan, Namasivayam
El Arifeen, Shams
Aryal, Dhana Raj
Asiruddin, Sk
Baqui, Abdullah
Barros, Aluisio J. D.
Benn, Christine S.
Bhandari, Vineet
Bhatnagar, Shinjini
Bhattacharya, Sohinee
Bhutta, Zulfiqar A.
Black, Robert E.
Blencowe, Hannah
Bose, Carl
Brown, Justin
Buehrer, Christoph
Carlo, Wally
Cecatti, Jose Guilherme
Cheung, Po-Yin
Clark, Robert
Colbourn, Tim
Conde-Agudelo, Agustin
Corbett, Erica
Czeizel, Andrew E.
Das, Abhik
Day, Louise Tina
Deal, Carolyn
Deorari, Ashok
Dilmen, Ugur
English, Mike
Engmann, Cyril
Esamai, Fabian
Fall, Caroline
Ferriero, Donna M.
Gisore, Peter
Hazir, Tabish
Higgins, Rosemary D.
Homer, Caroline S. E.
Hoque, D. E.
Irgens, Lorentz
Islam, M. T.
de Graft-Johnson, Joseph
Joshua, Martias Alice
Keenan, William
Khatoon, Soofia
Kieler, Helle
Kramer, Michael S.
Lackritz, Eve M.
Lavender, Tina
Lawintono, Laurensia
Luhanga, Richard
Marsh, David
McMillan, Douglas
McNamara, Patrick J.
Mol, Ben Willem J.
Molyneux, Elizabeth
Mukasa, G. K.
Mutabazi, Miriam
Nacul, Luis Carlos
Nakakeeto, Margaret
Narayanan, Indira
Olusanya, Bolajoko
Osrin, David
Paul, Vinod
Poets, Christian
Reddy, Uma M.
Santosham, Mathuram
Sayed, Rubayet
Schlabritz-Loutsevitch, Natalia E.
Singhal, Nalini
Smith, Mary Alice
Smith, Peter G.
Soofi, Sajid
Spong, Catherine Y.
Sultana, Shahin
Tshefu, Antoinette
van Bel, Frank
Gray, Lauren Vestewig
Waiswa, Peter
Wang, Wei
Williams, Sarah L. A.
Wright, Linda
Zaidi, Anita
Zhang, Yanfeng
Zhong, Nanbert
Zuniga, Isabel
Bahl, Rajiv
CA Neonatal Hlth Res Priority Setting
TI Setting research priorities to improve global newborn health and prevent
stillbirths by 2025
SO JOURNAL OF GLOBAL HEALTH
LA English
DT Article
ID SYSTEMATIC ANALYSIS; CHILD HEALTH; RESEARCH INVESTMENTS; PRETERM BIRTH;
TIME TRENDS; ACTION PLAN; DIARRHEA; BURDEN; PNEUMONIA; MORTALITY
AB Background In 2013, an estimated 2.8 million newborns died and 2.7 million were stillborn. A much greater number suffer from long term impairment associated with preterm birth, intrauterine growth restriction, congenital anomalies, and perinatal or infectious causes. With the approaching deadline for the achievement of the Millennium Development Goals (MDGs) in 2015, there was a need to set the new research priorities on newborns and stillbirth with a focus not only on survival but also on health, growth and development. We therefore carried out a systematic exercise to set newborn health research priorities for 2013-2025.
Methods We used adapted Child Health and Nutrition Research Initiative (CHNRI) methods for this prioritization exercise. We identified and approached the 200 most productive researchers and 400 program experts, and 132 of them submitted research questions online. These were collated into a set of 205 research questions, sent for scoring to the 600 identified experts, and were assessed and scored by 91 experts.
Results Nine out of top ten identified priorities were in the domain of research on improving delivery of known interventions, with simplified neonatal resuscitation program and clinical algorithms and improved skills of community health workers leading the list. The top 10 priorities in the domain of development were led by ideas on improved Kangaroo Mother Care at community level, how to improve the accuracy of diagnosis by community health workers, and perinatal audits. The 10 leading priorities for discovery research focused on stable surfactant with novel modes of administration for preterm babies, ability to diagnose fetal distress and novel tocolytic agents to delay or stop preterm labour.
Conclusion These findings will assist both donors and researchers in supporting and conducting research to close the knowledge gaps for reducing neonatal mortality, morbidity and long term impairment. WHO, SNL and other partners will work to generate interest among key national stakeholders, governments, NGOs, and research institutes in these priorities, while encouraging research funders to support them. We will track research funding, relevant requests for proposals and trial registers to monitor if the priorities identified by this exercise are being addressed
C1 [Yoshida, Sachiyo; Bahl, Rajiv] World Hlth Org, Newborn Child & Adolescent Hlth, Dept Maternal, 20 Ave Appia, CH-1211 Geneva 27, Switzerland.
[Martines, Jose] Univ Bergen, Ctr Int Hlth, Ctr Intervent Sci Maternal & Child Hlth, N-5020 Bergen, Norway.
[Lawn, Joy E.; Cousens, Simon] London Sch Hyg & Trop Med, London, England.
[Lawn, Joy E.; Wall, Stephen] Save Children, Saving Newborn Lives, Washington, DC USA.
[Souza, Joao Paulo] Univ Sao Paulo, Ribeirao Preto Sch Med, Dept Social Med, Sao Paulo, Brazil.
[Rudan, Igor] Univ Edinburgh, Sch Med, Ctr Populat Hlth Sci, Edinburgh, Midlothian, Scotland.
[Rudan, Igor] Univ Edinburgh, Sch Med, Global Hlth Acad, Edinburgh, Midlothian, Scotland.
[Aaby, Peter] Bandim Hlth Project Indepth Network, Bissau, Guinea Bissau.
[Adam, Ishag] Univ Khartoum, Fac Med, Khartoum, Sudan.
[Adhikari, Ramesh Kant] Kathmandu Med Coll, Kathmandu, Nepal.
[Ambalavanan, Namasivayam] Univ Alabama Birmingham, Dept Pediat, Birmingham, AL USA.
[El Arifeen, Shams] Int Ctr Diar rhoeal Dis Res, Ctr Child & Adolescent Hlth, Dhaka, Bangladesh.
[Aryal, Dhana Raj] Paropakar Matern & womens Hosp, Dept Neonatol, Kathmandu, Nepal.
[Asiruddin, Sk] Univ Res Co LLC, TRAct Bangladesh Project, Chevy Chase, MD USA.
[Baqui, Abdullah] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA.
[Barros, Aluisio J. D.] Univ Fed Pelotas, Ctr Pesquisas Epidemiol, Pelotas, Brazil.
[Benn, Christine S.] Univ Southern Denmark, Odense Univ Hosp, Res Ctr Vitamins, Odense, Denmark.
[Benn, Christine S.] Univ Southern Denmark, Odense Univ Hosp, Statens Serum Inst, Odense, Denmark.
[Bhandari, Vineet] Yale Univ, Sch Med, Program Perinatal Res, New Haven, CT 06520 USA.
[Bhatnagar, Shinjini] Translat Hlth Sci & Technol Inst, Pediat Biol Ctr, Pali, India.
[Bhattacharya, Sohinee] Univ Aberdeen, Aberdeen, Scotland.
[Bhutta, Zulfiqar A.] Aga Khan Univ, Ctr Excellence Women & Child Hlth, Karachi, Pakistan.
[Black, Robert E.] Johns Hopkins Bloomberg Sch Publ Hlth, Inst Int Programs, Baltimore, MD USA.
[Blencowe, Hannah] London Sch Hyg & Trop Med, London, England.
[Bose, Carl] Univ N Carolina, Chapel Hill Sch Med, Chapel Hill, NC USA.
[Brown, Justin] Thrasher Res Fund, Salt Lake City, UT USA.
[Buehrer, Christoph] Charles Univ Prague, Med Ctr, Dept Neonatol, Berlin, Germany.
[Carlo, Wally] Univ Alabama Birmingham, Birmingham, AL USA.
[Cecatti, Jose Guilherme] Univ Estadual Campinas, Sch Med Sci, Dept Obstet & Gynaecol, Campinas, SP, Brazil.
[Cheung, Po-Yin] Univ Alberta, Dept Pediat, Pharmacol & Surg, Edmonton, AB, Canada.
[Clark, Robert] Charities, New Orleans, LA USA.
[Colbourn, Tim] Univ Coll London Inst Global Hlth, London, England.
[Conde-Agudelo, Agustin] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, Natl Inst Hlth, Dept Hlth & Human Serv, Bethesda, MD USA.
[Corbett, Erica] Independent consultant maternal Hlth Res, Kigali, Rwanda.
[Czeizel, Andrew E.] Fdn Commun Control Hereditary Dis, Budapest, Hungary.
[Das, Abhik] RTI Int, Biostatist & Epidemiol, Res Triangle Pk, NC USA.
[Day, Louise Tina] LAMB Integrated Rural Hlth & Dev, Dinajpur, Bangladesh.
[Deal, Carolyn] Natl Inst Allergy & Infect Dis Natl Inst Hlth, Div Microbiol & Infect Dis, Salt Lake City, UT USA.
[Deorari, Ashok] All India Inst Med Sci, New Delhi, India.
[Dilmen, Ugur] Yildirim Beyazit Univ, Fac Med, Pediat & Neonatol, Ankara, Turkey.
[English, Mike] Univ Oxford, Nuffield Dept Med, Oxford, England.
[English, Mike] Univ Oxford, Dept Paediat, Oxford, England.
[English, Mike] KEMRi Wellcome Trust Res Programme, Nairobi, Kenya.
[Engmann, Cyril] Bill Melinda Gates Fdn, Newborn Hlth Family Hlth Div, Seattle, WA USA.
[Engmann, Cyril] Univ N Carolina, Sch Med & Publ Hlth, Chapel Hill, NC 27515 USA.
[Esamai, Fabian] Moi Univ, Sch Med, Eldoret, Kenya.
[Fall, Caroline] Univ Southampton, Med Res Council, Lifecourse Epidemiol Unit, Int Paediat Epidemiol, Southampton, Hants, England.
[Ferriero, Donna M.] UCSF Benioff Childrens Hosp, Dept Pediat, San Francisco, CA USA.
[Gisore, Peter] Moi Univ, Sch Med Child Hlth & Pediat, Eldoret, Kenya.
[Hazir, Tabish] Childrens Hosp, Pakistan Inst Med Sci, Lahore, Pakistan.
[Higgins, Rosemary D.] Eunice Kennedy Shriver NICHD Neonatal Res Network, Pregnancy & Perinatol Branch, Natl Inst Hlth, Bethesda, MD USA.
[Homer, Caroline S. E.] Univ Technol, Ctr Midwifery Child & Family Hlth, Sydney, NSW, Australia.
[Hoque, D. E.] Int Ctr Diarrhoeal Dis Res, Ctr Child & Adolescent Hlth, Dhaka, Bangladesh.
[Irgens, Lorentz] Univ Bergen, Bergen, Norway.
[Irgens, Lorentz] Norwegian Inst Publ Hlth, Bergen, Norway.
[Islam, M. T.] Japan Int Cooperat Agcy JICA, Dhaka, Bangladesh.
[de Graft-Johnson, Joseph] Save Children, Fairfield, CT USA.
[Joshua, Martias Alice] Zomba Cent Hosp, Minist Hlth, Zomba, Malawi.
[Keenan, William] St Louis Univ, St Louis, MO USA.
[Khatoon, Soofia] Shaheed Suhrawardy Med Coll, Paediat & Head Dept, Dhaka, Bangladesh.
[Kieler, Helle] Karolinska Inst, Ctr Pharmacoepidemiol, Solna, Sweden.
[Kramer, Michael S.] McGill Univ, Fac Med, Biostat & Occupat Hlth, Dept Pediat & Epidemiol, Montreal, PQ, Canada.
[Lackritz, Eve M.] Global Alliance Prevent Prematur & Stillbirth GAP, Seattle, WA USA.
[Lavender, Tina] Univ Manchester, Sch Nursing Midwifery & Social Work, Manchester, Lancs, England.
[Lawintono, Laurensia] Indonesian Midw Assoc, Jakarta, Indonesia.
[Luhanga, Richard] Save Children, Lilongwe, Malawi.
[Marsh, David] Save Children, Fairfield, CT USA.
[McMillan, Douglas] Dalhousie Univ, Dept Paediat, Halifax, NS, Canada.
[McNamara, Patrick J.] Univ Toronto, Dept Paediat & Physiol, Toronto, ON, Canada.
[McNamara, Patrick J.] Hosp Sick Children, Physiol & Expt Med program, Toronto, ON, Canada.
[Mol, Ben Willem J.] Acad Med Ctr, Dept Obstet & Gynaecol, Amsterdam, Netherlands.
[Molyneux, Elizabeth] Coll Med, Paediat & Child Hlth, Lilongwe, Malawi.
[Mukasa, G. K.] Int Baby Food Act Network, Kampala, Uganda.
[Mutabazi, Miriam] STRIDES Family Hlth, Management Sci Hlth, Kampala, Uganda.
[Nacul, Luis Carlos] London Sch Hyg & Trop Med, Fac Infect & Trop Dis, London, England.
[Nakakeeto, Margaret] Kampala Childrens Hosp Ltd & Childhealth Advocacy, Kampala, Uganda.
[Narayanan, Indira] United States Agcy Int Dev, Maternal & Child Hlth Integrated Program, Washington, DC USA.
[Olusanya, Bolajoko] Ctr Healthy Start Initiat, Lagos, Nigeria.
[Osrin, David] UCL, Inst Global Hlth, Wellcome Trust Senior Res Fellow Clin Sci, London, England.
[Paul, Vinod] All India Inst Med Sci, Patna, Bihar, India.
[Poets, Christian] Univ Tubingen, Tubingen, Germany.
[Reddy, Uma M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Dev Natl Inst Hlth, Cambridge, MD USA.
[Santosham, Mathuram] Johns Hopkins Bloomberg, Sch Publ Hlth, Ctr Amer Indian Hlth, Baltimore, MD USA.
[Sayed, Rubayet] Save Children, Dhaka, Bangladesh.
[Schlabritz-Loutsevitch, Natalia E.] Univ Tennessee, Hlth Sci Ctr, Dept Obstet & Gynecol, Knoxville, TN 37996 USA.
[Singhal, Nalini] Univ Calgary, Calgary, AB, Canada.
[Smith, Mary Alice] Univ Georgia, Dept Environm Hlth Sci, Athens, GA 30602 USA.
[Smith, Peter G.] London Sch Hyg & Trop Med, Trop Epidemiol Grp, London, England.
[Soofi, Sajid] Aga Khan Univ, Women & Child Hlth Div, Dept Pediat & Child Hlth, Karachi, Pakistan.
[Spong, Catherine Y.; Zaidi, Anita] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
[Sultana, Shahin] Minist Hlth & Family Welf, Natl Inst Populat Res & Training NIPORT, Dhaka, Bangladesh.
[Tshefu, Antoinette] Univ Kinshasa, Sch Med, Kinshasa Sch Publ Hlth, Kinshasa, DEM REP CONGO.
[van Bel, Frank] Univ Utrecht, Dept Neonatol, Utrecht, Netherlands.
[Gray, Lauren Vestewig] Rice Univ, Inst Global Hlth Technol, Houston, TX 77251 USA.
[Waiswa, Peter] Karolinska Inst, Div Global Hlth, Stockholm, Sweden.
[Williams, Sarah L. A.] Edith Cowan Univ, Sch Med Sci, Churchlands, WA 6018, Australia.
[Wright, Linda] Capital Med Univ, Sch Publ Hlth, Beijing, Peoples R China.
[Wright, Linda] Save Children UK, London, England.
[Zaidi, Anita] Aga Khan Univ, Karachi, Pakistan.
[Zhang, Yanfeng] Capital Inst Paediat, Dept Integrated Early Childhood Dev, Beijing, Peoples R China.
[Zhong, Nanbert] New York State Inst Basic Res Dev Disabil, Lab Dev Genet, New York, NY USA.
[Zuniga, Isabel] Medecins Sans Frontieres, Brussels, Belgium.
RP Bahl, R (reprint author), World Hlth Org, Newborn Child & Adolescent Hlth, Dept Maternal, 20 Ave Appia, CH-1211 Geneva 27, Switzerland.
EM bahlr@who.int
RI Souza, Joao Paulo/G-1982-2010;
OI Souza, Joao Paulo/0000-0002-2288-4244; Homer,
Caroline/0000-0002-7454-3011
FU Save the Children
FX This work was supported by Save the Children.
NR 35
TC 0
Z9 0
U1 1
U2 98
PU UNIV EDINBURGH, GLOBAL HEALTH SOC
PI EDINBURGH
PA CENTRE POPULATION HEALTH SCIENCES, TEVIOT PL, EDINBURGH, EH8 9AG,
ENGLAND
SN 2047-2978
EI 2047-2986
J9 J GLOB HEALTH
JI J. Glob. Health
PD JUN
PY 2016
VL 6
IS 1
AR 010508
DI 10.7189/jogh.06.010508
PG 10
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA EO8YM
UT WOS:000396976400026
PM 26401272
ER
PT J
AU Pholphirul, P
Teimtad, S
AF Pholphirul, Piriya
Teimtad, Siwat
TI Economics of Pre-Primary Education in Thailand
SO APPLIED ECONOMICS JOURNAL
LA English
DT Article
DE Pre-Primary Education; Long-Term Impacts; Education Performance;
Thailand
ID PRIMARY-SCHOOL; OUTCOMES; LONG
AB Several research papers have assessed the long-term benefits of pre-primary education in terms of academic performance and labor market outcomes. This study analyzes data obtained from the Program for International Student Assessment (PISA) to estimate the effects of preschool enrollment of Thai students on producing long-term benefits in their academic performance. Results show that a mother's educational attainment has a significant impact on the decision to enroll her child in preschool. Regarding the long-term benefits, our findings show that pre-primary education bears a significant and positive association with cognitive skills in all three areas of literacy tested under PISA, namely, reading, mathematics, and the sciences. Regarding the economic status of students' families, results indicate that the benefits of pre-primary education in cognitive skill improvement tend to be greatest in the case of students from low-to middle-income families. Evidence supports the promotion of long-term benefits of pre-primary education and, thus, the universal early childhood education policy. In particular, support should be given to childhood education programs that specifically target children from disadvantaged groups and low-income households.
C1 [Pholphirul, Piriya; Teimtad, Siwat] NIDA, Grad Sch Dev Econ, Bangkok 10240, Thailand.
[Pholphirul, Piriya] Int Coll Natl Inst Dev Adm ICO NIDA, Bangkok 10240, Thailand.
RP Pholphirul, P (reprint author), NIDA, Grad Sch Dev Econ, Bangkok 10240, Thailand.; Pholphirul, P (reprint author), Int Coll Natl Inst Dev Adm ICO NIDA, Bangkok 10240, Thailand.
EM pholphir@hotmail.com; tae.siwat@gmail.com
FU Wisdom Society for Public Opinion Research of Thailand
FX This paper is financially support by The Wisdom Society for Public
Opinion Research of Thailand under the management of the CP All, Public,
Company.
NR 31
TC 0
Z9 0
U1 2
U2 2
PU KASERSART UNIV, FAC ECONOMICS
PI BANGKOK
PA CENTER APPLIED ECONOMICS RESEARCH, 50 PHAHON YOTHIN RD, JATUJAK,
BANGKOK, 10900, THAILAND
SN 0858-9291
J9 APPL ECON J
JI Appl. Econ. J.
PD JUN
PY 2016
VL 23
IS 1
BP 1
EP 34
PG 34
WC Economics
SC Business & Economics
GA EJ7PI
UT WOS:000393414200002
ER
PT J
AU Patmasiriwat, D
Hengpatana, S
AF Patmasiriwat, Direk
Hengpatana, Suwimon
TI Income, Saving, and Wealth of Thai Rural Households: A Case Study of
Saving Adequacies
SO APPLIED ECONOMICS JOURNAL
LA English
DT Article
DE Income; saving; wealth; saving inadequacy; socio-economic factors; rural
household; Thailand
AB This paper investigates the savings and wealth of Thai rural households with an emphasis on the issue of saving inadequacies. We use the household survey conducted by the National Statistical Office in 2009 as a database. First, we hypothesize an interrelationship between household income, saving, and assets. Further, we estimate the scope of the relationship using an econometric technique and examine savings predicted over the household's lifecycle. Our findings indicate that: (i) approximately 29% of Thai rural households overspent their income; indeed, this group failed to save and incurred negative savings, (ii) 47% of Thai rural households inadequately saved due to a "weak definition" which signifies the amount saved is inadequate or too little to cope with future risks and uncertainties. Calculations related to the probabilities of saving inadequacies compared age-cohorts, occupations, and levels of education. The last section discusses long-term implications of saving inadequacies, and limitations of the model for improving saving practices within Thai rural households.
C1 [Patmasiriwat, Direk] NIDA, Sch Dev Econ, Seri Thai Rd, Bangkok 10240, Thailand.
[Hengpatana, Suwimon] Srinakharinwirot Univ, Sch Econ & Publ Policy, Bangkok 10110, Thailand.
RP Patmasiriwat, D (reprint author), NIDA, Sch Dev Econ, Seri Thai Rd, Bangkok 10240, Thailand.
EM direk.p@nida.ac.th; suwimonh@g.swu.ac.th
NR 6
TC 0
Z9 0
U1 0
U2 0
PU KASERSART UNIV, FAC ECONOMICS
PI BANGKOK
PA CENTER APPLIED ECONOMICS RESEARCH, 50 PHAHON YOTHIN RD, JATUJAK,
BANGKOK, 10900, THAILAND
SN 0858-9291
J9 APPL ECON J
JI Appl. Econ. J.
PD JUN
PY 2016
VL 23
IS 1
BP 75
EP 91
PG 17
WC Economics
SC Business & Economics
GA EJ7PI
UT WOS:000393414200005
ER
PT J
AU Muthigi, A
George, AK
Brancato, SJ
Agarwal, PK
AF Muthigi, Akhil
George, Arvin K.
Brancato, Sam J.
Agarwal, Piyush K.
TI Novel immunotherapeutic approaches to the treatment of urothelial
carcinoma
SO THERAPEUTIC ADVANCES IN UROLOGY
LA English
DT Review
DE immunotherapy; NMIBC; urothelial carcinoma
ID BACILLUS-CALMETTE-GUERIN; SUPERFICIAL BLADDER-CANCER;
TRANSITIONAL-CELL-CARCINOMA; CHIMERIC ANTIGEN RECEPTOR; MODIFIED
T-CELLS; MYCOBACTERIUM-BOVIS; IFN-GAMMA; INTRAVESICAL TREATMENT;
ONCOLYTIC ADENOVIRUS; BCG IMMUNOTHERAPY
AB Immunotherapy has long played a role in urothelial cancers with the use of bacille Calmette Guerin (BCG) being a mainstay in the treatment of nonmuscle invasive bladder cancer. Novel therapeutic approaches have not significantly impacted mortality in this population and so a renaissance in immunotherapy has resulted. This includes recombinant BCG, oncolytic viruses, monoclonal antibodies, vaccines, and adoptive T-cell therapy. Herein, we provide a review of the current state of the art and future therapies regarding immunotherapeutic strategies for urothelial carcinoma.
C1 [Muthigi, Akhil; George, Arvin K.; Brancato, Sam J.; Agarwal, Piyush K.] NCI, Urol Oncol Branch, NIH, Bldg 10 Hatfield CRC,Room 2-5952, Bethesda, MD 20892 USA.
RP Agarwal, PK (reprint author), NCI, Urol Oncol Branch, NIH, Bldg 10 Hatfield CRC,Room 2-5952, Bethesda, MD 20892 USA.
EM piyush.agarwal@nih.gov
RI Brancato, Sam/K-3266-2014
OI Brancato, Sam/0000-0002-3760-5818
FU National Institutes of Health (NIH), National Cancer Institute; NIH
FX This research was supported by the Intramural Research Program of the
National Institutes of Health (NIH), National Cancer Institute.; This
research was made possible through the National Institutes of Health
(NIH) Medical Research Scholars Program, a public-private partnership
supported jointly by the NIH and generous contributions to the
Foundation for the NIH from the Doris Duke Charitable Foundation,
American Association for Dental Research, Howard Hughes Medical
Institute, and the Colgate-Palmolive Company, as well as alumni of
student research programs and other individual supporters.
NR 73
TC 0
Z9 0
U1 0
U2 0
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 1756-2872
EI 1756-2880
J9 THER ADV UROL
JI Ther. Adv. Urol.
PD JUN
PY 2016
VL 8
IS 3
BP 203
EP 214
DI 10.1177/1756287216628784
PG 12
WC Urology & Nephrology
SC Urology & Nephrology
GA EK2EX
UT WOS:000393741700005
PM 27247630
ER
PT J
AU Feng, S
Bucuvalas, J
Demetris, A
Spain, K
Kanaparthi, S
Magee, J
Mazariegos, G
AF Feng, S.
Bucuvalas, J.
Demetris, A.
Spain, K.
Kanaparthi, S.
Magee, J.
Mazariegos, G.
CA iWITH Investigators
TI Primary Outcome of iWITH: A Multi-Center Clinical Trial of Complete
Immunosuppression Withdrawal (ISW) in Stable Pediatric Liver Transplant
(LT) Recipients
SO AMERICAN JOURNAL OF TRANSPLANTATION
LA English
DT Meeting Abstract
CT American Transplant Congress
CY JUN 11-15, 2016
CL Boston, MA
C1 [Feng, S.] UCSF, San Francisco, CA USA.
[Bucuvalas, J.] CCHMC, Cincinnati, OH USA.
[Demetris, A.; Mazariegos, G.] Univ Pitt, Pittsburgh, PA USA.
[Spain, K.] Rho, Chapel Hill, NC USA.
[Kanaparthi, S.] ITN, Bethesda, MD USA.
[Magee, J.] Univ Mich, Ann Arbor, MI USA.
[iWITH Investigators] NIDDK, NIAID, ITN, Bethesda, MD 20892 USA.
NR 0
TC 1
Z9 1
U1 1
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1600-6135
EI 1600-6143
J9 AM J TRANSPLANT
JI Am. J. Transplant.
PD JUN
PY 2016
VL 16
SU 3
SI SI
MA 185.1
BP 269
EP 269
PG 1
WC Surgery; Transplantation
SC Surgery; Transplantation
GA DW1AB
UT WOS:000383373902186
ER
PT J
AU Zuckerman, W
Feingold, B
Zeevi, A
Bentlejewski, C
Addonizio, L
Blume, E
Canter, C
Dipchand, A
Hsu, D
Shaddy, R
Mahle, W
Much, K
Armstrong, B
Ikle, D
Diop, H
Odim, J
Webber, S
AF Zuckerman, W.
Feingold, B.
Zeevi, A.
Bentlejewski, C.
Addonizio, L.
Blume, E.
Canter, C.
Dipchand, A.
Hsu, D.
Shaddy, R.
Mahle, W.
Much, K.
Armstrong, B.
Ikle, D.
Diop, H.
Odim, J.
Webber, S.
TI Solid Phase Assay Demonstrates High Rates of Allosensitization in
Pediatric Heart Recipients.
SO AMERICAN JOURNAL OF TRANSPLANTATION
LA English
DT Meeting Abstract
CT American Transplant Congress
CY JUN 11-15, 2016
CL Boston, MA
C1 [Zuckerman, W.; Addonizio, L.] Columbia Univ, Nyc, NY USA.
[Feingold, B.; Zeevi, A.; Bentlejewski, C.] Univ Pittsburgh, Pittsburgh, PA USA.
[Blume, E.] Boston Childrens Hosp, Boston, MA USA.
[Canter, C.] Washington Univ, St Louis, MO USA.
[Dipchand, A.] Sick Kids, Toronto, ON, Canada.
[Hsu, D.] Montefiore, Childrens Hosp, Nyc, NY USA.
[Shaddy, R.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA.
[Mahle, W.] CHOA, Atlanta, GA USA.
[Much, K.; Armstrong, B.; Ikle, D.] Rho, Chapel Hill, NC USA.
[Diop, H.; Odim, J.] NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Webber, S.] Vanderbilt Univ, 221 Kirkland Hall, Nashville, TN 37235 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1600-6135
EI 1600-6143
J9 AM J TRANSPLANT
JI Am. J. Transplant.
PD JUN
PY 2016
VL 16
SU 3
SI SI
MA 15
BP 210
EP 210
PG 1
WC Surgery; Transplantation
SC Surgery; Transplantation
GA DW1AB
UT WOS:000383373902015
ER
PT J
AU Shaked, A
Feng, S
Punch, J
Reyes, J
Levitsky, J
Klintmalm, G
Kopetskie, H
DesMarais, M
Priore, A
Bridges, N
Sayre, P
AF Shaked, A.
Feng, S.
Punch, J.
Reyes, J.
Levitsky, J.
Klintmalm, G.
Kopetskie, H.
DesMarais, M.
Priore, A.
Bridges, N.
Sayre, P.
TI Early Post-Transplant Immunosuppression (IS) Withdrawal - Final Outcomes
of the ITN030ST AWISH Study
SO AMERICAN JOURNAL OF TRANSPLANTATION
LA English
DT Meeting Abstract
CT American Transplant Congress
CY JUN 11-15, 2016
CL Boston, MA
C1 [Shaked, A.] UPenn, Philadelphia, PA USA.
[Feng, S.; DesMarais, M.; Sayre, P.] UCSF, San Francisco, CA USA.
[Punch, J.] Univ Michigan, Ann Arbor, MI 48109 USA.
[Reyes, J.] Univ Washington, Seattle, WA 98195 USA.
[Levitsky, J.] Northwestern, Chicago, IL USA.
[Klintmalm, G.] Baylor, Dallas, TX USA.
[Kopetskie, H.] RhoFed, Chapel Hill, NC USA.
[Priore, A.; Bridges, N.] NIAID, 9000 Rockville Pike, Bethesda, MD 20892 USA.
NR 0
TC 1
Z9 1
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1600-6135
EI 1600-6143
J9 AM J TRANSPLANT
JI Am. J. Transplant.
PD JUN
PY 2016
VL 16
SU 3
SI SI
MA 185
BP 269
EP 269
PG 1
WC Surgery; Transplantation
SC Surgery; Transplantation
GA DW1AB
UT WOS:000383373902185
ER
PT J
AU Suarez-Fuentes, C
Broin, O
Bao, Y
Akalin, E
AF Suarez-Fuentes, C.
Broin, O.
Bao, Y.
Akalin, E.
TI Effect of Angiotensin Converting Enzyme Inhibitor (ACEI) or Angiotensin
Receptor Blockade (ARB) Exposure on Intragraft Gene Expression of Kidney
Transplant Patients
SO AMERICAN JOURNAL OF TRANSPLANTATION
LA English
DT Meeting Abstract
CT American Transplant Congress
CY JUN 11-15, 2016
CL Boston, MA
C1 [Suarez-Fuentes, C.; Bao, Y.; Akalin, E.] Montefiore Med Ctr, Kidney Transplant, 111 E 210th St, Bronx, NY 10467 USA.
[Suarez-Fuentes, C.; Akalin, E.] Albert Einstein Coll Med, Bronx, NY 10467 USA.
[Broin, O.] Natl Univ Ireland Galway Univ, Galway, Ireland.
[Suarez-Fuentes, C.] NIH, Bldg 10, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1600-6135
EI 1600-6143
J9 AM J TRANSPLANT
JI Am. J. Transplant.
PD JUN
PY 2016
VL 16
SU 3
SI SI
MA 341
BP 323
EP 324
PG 2
WC Surgery; Transplantation
SC Surgery; Transplantation
GA DW1AB
UT WOS:000383373902342
ER
PT J
AU Chan, J
Singh, A
Corcoran, P
Thomas, M
Lewis, B
Ayares, D
Horvath, K
Mohiuddin, M
AF Chan, J.
Singh, A.
Corcoran, P.
Thomas, M., III
Lewis, B.
Ayares, D.
Horvath, K.
Mohiuddin, M.
TI Inclusion of Human Tissue Factor Pathway Inhibitor or Thrombomodulin
Transgenes Attenuates Critical Consumptive Thrombocytopenia in Cardiac
Xenotransplantation.
SO AMERICAN JOURNAL OF TRANSPLANTATION
LA English
DT Meeting Abstract
CT American Transplant Congress
CY JUN 11-15, 2016
CL Boston, MA
C1 [Chan, J.; Singh, A.; Corcoran, P.; Horvath, K.; Mohiuddin, M.] NHLBI, Cardiothorac Surg Res Program, NIH, Bldg 10, Bethesda, MD 20892 USA.
[Thomas, M., III; Lewis, B.] NIH, Div Vet Resources, Bldg 10, Bethesda, MD 20892 USA.
[Ayares, D.] Revivicor Inc, Blacksburg, VA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1600-6135
EI 1600-6143
J9 AM J TRANSPLANT
JI Am. J. Transplant.
PD JUN
PY 2016
VL 16
SU 3
SI SI
MA 361
BP 329
EP 329
PG 1
WC Surgery; Transplantation
SC Surgery; Transplantation
GA DW1AB
UT WOS:000383373902361
ER
PT J
AU Horvath, K
Singh, A
Chan, J
Thomas, M
Lewis, B
Ayares, D
Corcoran, P
Mohiuddin, M
AF Horvath, K.
Singh, A.
Chan, J.
Thomas, M.
Lewis, B.
Ayares, D.
Corcoran, P.
Mohiuddin, M.
TI The Impact of Sequential Gene Modifications on Cardiac Xenograft
Survival
SO AMERICAN JOURNAL OF TRANSPLANTATION
LA English
DT Meeting Abstract
CT American Transplant Congress
CY JUN 11-15, 2016
CL Boston, MA
C1 [Horvath, K.; Singh, A.; Chan, J.; Corcoran, P.; Mohiuddin, M.] NHLBI, CSRP, NIH, Bldg 10, Bethesda, MD 20892 USA.
[Thomas, M.; Lewis, B.] NIH, DVR, ORS, Bldg 10, Bethesda, MD 20892 USA.
[Lewis, B.; Ayares, D.] Revivicor Inc, Blacksburg, VA USA.
NR 0
TC 1
Z9 1
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1600-6135
EI 1600-6143
J9 AM J TRANSPLANT
JI Am. J. Transplant.
PD JUN
PY 2016
VL 16
SU 3
SI SI
MA 360
BP 329
EP 329
PG 1
WC Surgery; Transplantation
SC Surgery; Transplantation
GA DW1AB
UT WOS:000383373902360
ER
PT J
AU Singh, A
Chan, J
Corcoran, P
Lewis, B
Thomas, M
Ayares, D
Horvath, K
Mohiuddin, M
AF Singh, A.
Chan, J.
Corcoran, P.
Lewis, B.
Thomas, M.
Ayares, D.
Horvath, K.
Mohiuddin, M.
TI Costimulation Blockade by Anti CD40 Antibody Prevents Humoral and
Cellular Rejection of Heterotopic Pig Cardiac Xenograft.
SO AMERICAN JOURNAL OF TRANSPLANTATION
LA English
DT Meeting Abstract
CT American Transplant Congress
CY JUN 11-15, 2016
CL Boston, MA
C1 [Singh, A.; Chan, J.; Corcoran, P.; Horvath, K.; Mohiuddin, M.] CSRP NHLBI, NIH, Bethesda, MD USA.
[Lewis, B.; Thomas, M.] NIH, DVR ORS, Bldg 10, Bethesda, MD 20892 USA.
[Ayares, D.] Revivicor Inc, Blacksburg, VA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1600-6135
EI 1600-6143
J9 AM J TRANSPLANT
JI Am. J. Transplant.
PD JUN
PY 2016
VL 16
SU 3
SI SI
MA 362
BP 329
EP 330
PG 2
WC Surgery; Transplantation
SC Surgery; Transplantation
GA DW1AB
UT WOS:000383373902362
ER
PT J
AU Webber, S
Addonizio, L
Blume, E
Dipchand, A
Shaddy, R
Feingold, B
Canter, C
Hsu, D
Mahle, W
Zeevi, A
Much, K
Ikle, D
Diop, H
Odim, J
AF Webber, S.
Addonizio, L.
Blume, E.
Dipchand, A.
Shaddy, R.
Feingold, B.
Canter, C.
Hsu, D.
Mahle, W.
Zeevi, A.
Much, K.
Ikle, D.
Diop, H.
Odim, J.
CA CTOTC-04 Investigators
TI Pediatric Heart Transplantation Across a Positive Cross-Match Is
Associated with High Rates of AMR but No Difference in Short Term Graft
Loss, Dysfunction and Death (CTOTC-04 study).
SO AMERICAN JOURNAL OF TRANSPLANTATION
LA English
DT Meeting Abstract
CT American Transplant Congress
CY JUN 11-15, 2016
CL Boston, MA
C1 [Webber, S.] Vanderbilt, Nashville, TN USA.
[Addonizio, L.] Columbia Univ, Nyc, NY USA.
[Blume, E.] Boston Childrens, Boston, MA USA.
[Dipchand, A.] Sick Kids, Toronto, ON, Canada.
[Shaddy, R.] CHOP, Philadelphia, PA USA.
[Feingold, B.; Zeevi, A.] CHP UPMC, Pittsburgh, PA USA.
[Canter, C.] Washington Univ, St Louis, MO USA.
[Hsu, D.] Montefiore, Childrens Hosp, Nyc, NY USA.
[Mahle, W.] CHOA, Atlanta, GA USA.
[Much, K.; Ikle, D.] Rho, Chapel Hill, NC USA.
[Diop, H.; CTOTC-04 Investigators] NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1600-6135
EI 1600-6143
J9 AM J TRANSPLANT
JI Am. J. Transplant.
PD JUN
PY 2016
VL 16
SU 3
SI SI
MA 572
BP 331
EP 331
PG 1
WC Surgery; Transplantation
SC Surgery; Transplantation
GA DW1AB
UT WOS:000383373902367
ER
PT J
AU Mannon, R
Stock, P
Mehta, A
Ikle, D
Watson, N
Bridges, N
Robien, M
Newell, K
AF Mannon, R.
Stock, P.
Mehta, A.
Ikle, D.
Watson, N.
Bridges, N.
Robien, M.
Newell, K.
TI Avoidance of CNI and Steroids Using Belatacept - A Preliminary Report of
CTOT-16.
SO AMERICAN JOURNAL OF TRANSPLANTATION
LA English
DT Meeting Abstract
CT American Transplant Congress
CY JUN 11-15, 2016
CL Boston, MA
C1 [Mannon, R.] UAB, Birmingham, AL USA.
[Stock, P.] UCSF, San Francisco, CA USA.
[Mehta, A.; Newell, K.] Emory, Atlanta, GA USA.
[Ikle, D.] Rho, Chapel Hill, NC USA.
[Watson, N.; Bridges, N.; Robien, M.] NIAID, 9000 Rockville Pike, Bethesda, MD 20892 USA.
NR 0
TC 1
Z9 1
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1600-6135
EI 1600-6143
J9 AM J TRANSPLANT
JI Am. J. Transplant.
PD JUN
PY 2016
VL 16
SU 3
SI SI
MA 566
BP 401
EP 402
PG 2
WC Surgery; Transplantation
SC Surgery; Transplantation
GA DW1AB
UT WOS:000383373902571
ER
PT J
AU Mohiuddin, M
Singh, A
Chan, J
Corcoran, P
Thomas, M
Lewis, B
Ayares, D
Horvath, K
AF Mohiuddin, M.
Singh, A.
Chan, J.
Corcoran, P.
Thomas, M., III
Lewis, B.
Ayares, D.
Horvath, K.
TI Long Term Heterotopic Cardiac Xenograft Survival from Donor Pigs with
Six Gene Modifications
SO AMERICAN JOURNAL OF TRANSPLANTATION
LA English
DT Meeting Abstract
CT American Transplant Congress
CY JUN 11-15, 2016
CL Boston, MA
C1 [Mohiuddin, M.; Singh, A.; Chan, J.; Corcoran, P.; Horvath, K.] NHLBI, CSRP, NIH, Bldg 10, Bethesda, MD 20892 USA.
[Thomas, M., III; Lewis, B.] NIH, DVR, RS, Bldg 10, Bethesda, MD 20892 USA.
[Ayares, D.] Revivicor Inc, Blacksburgh, VA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1600-6135
EI 1600-6143
J9 AM J TRANSPLANT
JI Am. J. Transplant.
PD JUN
PY 2016
VL 16
SU 3
SI SI
MA B37
BP 512
EP 512
PG 1
WC Surgery; Transplantation
SC Surgery; Transplantation
GA DW1AB
UT WOS:000383373903339
ER
PT J
AU Feng, XS
Juan, AH
Wang, HA
Ko, KD
Zare, H
Sartorelli, V
AF Feng, Xuesong
Juan, Aster H.
Wang, Hongjun A.
Ko, Kyung Dae
Zare, Hossein
Sartorelli, Vittorio
TI Polycomb Ezh2 controls the fate of GABAergic neurons in the embryonic
cerebellum
SO DEVELOPMENT
LA English
DT Article
DE Polycomb; Ezh2; PRC2; Cerebellum; Neurogenesis; Purkinje cells
ID RECEPTOR ROR ALPHA; LARGE GENE LISTS; STEM-CELLS; SONIC HEDGEHOG;
RHOMBIC-LIP; HISTONE METHYLTRANSFERASE; ISTHMIC ORGANIZER; MOUSE
DEVELOPMENT; NERVOUS-SYSTEM; PURKINJE-CELLS
AB Although the genetic interactions between signaling pathways and transcription factors have been largely decoded, much remains to be learned about the epigenetic regulation of cerebellar development. Here, we report that cerebellar deletion of Ezh2, the methyltransferase subunit of the PRC2 complex, results in reduced H3K27me3 and profound transcriptional dysregulation, including that of a set of transcription factors directly involved in cerebellar neuronal cell-type specification and differentiation. Such transcriptional changes lead to increased GABAergic interneurons and decreased Purkinje cells. Transcriptional changes also inhibit the proliferation of granule precursor cells derived from the rhombic lip. The loss of both cell types ultimately results in cerebellar hypoplasia. These findings indicate Ezh2/PRC2 plays crucial roles in regulating neurogenesis from both cerebellar germinal zones.
C1 [Feng, Xuesong; Juan, Aster H.; Wang, Hongjun A.; Ko, Kyung Dae; Zare, Hossein; Sartorelli, Vittorio] NIAMSD, Lab Muscle Stem Cells & Gene Regulat, NIH, 50 South Dr, Bethesda, MD 20892 USA.
RP Sartorelli, V (reprint author), NIAMSD, Lab Muscle Stem Cells & Gene Regulat, NIH, 50 South Dr, Bethesda, MD 20892 USA.
EM sartorev@mail.nih.gov
FU Intramural Research Program of the National Institute of Arthritis and
Musculoskeletal and Skin Diseases (NIAMS) at the National Institutes of
Health
FX This work was supported by the Intramural Research Program of the
National Institute of Arthritis and Musculoskeletal and Skin Diseases
(NIAMS) at the National Institutes of Health. Deposited in PMC for
release after 12 months.
NR 78
TC 0
Z9 0
U1 2
U2 2
PU COMPANY OF BIOLOGISTS LTD
PI CAMBRIDGE
PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL,
CAMBS, ENGLAND
SN 0950-1991
EI 1477-9129
J9 DEVELOPMENT
JI Development
PD JUN 1
PY 2016
VL 143
IS 11
BP 1971
EP 1980
DI 10.1242/dev.132902
PG 10
WC Developmental Biology
SC Developmental Biology
GA EE4QG
UT WOS:000389588800014
PM 27068104
ER
PT J
AU Hudak, ML
Park, CH
Annett, RD
Hale, DE
McGovern, PM
McLaughlin, TJ
Dole, N
Kaar, JL
Balsam, MJ
AF Hudak, Mark L.
Park, Christina H.
Annett, Robert D.
Hale, Daniel E.
McGovern, Patricia M.
McLaughlin, Thomas J.
Dole, Nancy
Kaar, Jill L.
Balsam, Marion J.
TI The National Children's Study: An Introduction and Historical Overview
SO PEDIATRICS
LA English
DT Article
ID RECRUITMENT
AB The National Children's Study (NCS) was an ambitious attempt to map children's health and development in a large representative group of children in the United States. In this introduction, we briefly review the background of the NCS and the history of the multiple strategies that were tested to recruit women and children. Subsequent articles then detail the protocols and outcomes of 4 of the recruitment strategies. It is hoped that lessons learned from these attempts to define a study protocol that could achieve the initial aims of the NCS will inform future efforts to conceptualize and execute strategies to provide generalizable insights on the longitudinal health of our nation's children.
C1 [Hudak, Mark L.] Univ Florida, Coll Med Jacksonville, Dept Pediat, 653-1 W 8th St, Jacksonville, FL 32209 USA.
[Park, Christina H.; Balsam, Marion J.] NICHHD, Bethesda, MD 20892 USA.
[Annett, Robert D.] Univ Mississippi, Med Ctr, Div Child Dev, Jackson, MS 39216 USA.
[Hale, Daniel E.] Univ Texas Hlth Sci Ctr San Antonio, Div Endocrinol & Diabet, San Antonio, TX 78229 USA.
[McGovern, Patricia M.] Univ Minnesota, Sch Publ Hlth, Div Environm Hlth Serv, Minneapolis, MN USA.
[McLaughlin, Thomas J.] Univ Massachusetts, Dept Pediat, Worcester, MA 01605 USA.
[Dole, Nancy] Univ N Carolina, Carolina Populat Ctr, Chapel Hill, NC USA.
[Kaar, Jill L.] Univ Colorado, Sch Med, Dept Pediat, Denver, CO USA.
RP Hudak, ML (reprint author), Univ Florida, Coll Med Jacksonville, Dept Pediat, 653-1 W 8th St, Jacksonville, FL 32209 USA.
EM mark.hudak@jax.ufl.edu
FU NICHD; National Institutes of Health (NIH)
FX Supported in part by NICHD contracts. Funded by the National Institutes
of Health (NIH).
NR 7
TC 0
Z9 0
U1 0
U2 0
PU AMER ACAD PEDIATRICS
PI ELK GROVE VILLAGE
PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA
SN 0031-4005
EI 1098-4275
J9 PEDIATRICS
JI Pediatrics
PD JUN
PY 2016
VL 137
SU 4
AR e20154410B
DI 10.1542/peds.2015-4410B
PG 6
WC Pediatrics
SC Pediatrics
GA EE2KQ
UT WOS:000389413300002
PM 27251867
ER
PT J
AU McLaughlin, TJ
Aupont, O
Kozinetz, CA
Hubble, D
Moore-Simas, TA
Davis, D
Park, C
Brenner, R
Sepavich, D
Felice, M
Caviness, C
Downs, T
Selwyn, BJ
Forman, MR
AF McLaughlin, Thomas J.
Aupont, Onesky
Kozinetz, Claudia A.
Hubble, David
Moore-Simas, Tiffany A.
Davis, Deborah
Park, Christina
Brenner, Ruth
Sepavich, Deidre
Felice, Marianne
Caviness, Chantal
Downs, Tim
Selwyn, Beatrice J.
Forman, Michele R.
TI Multilevel Provider-Based Sampling for Recruitment of Pregnant Women and
Mother-Newborn Dyads
SO PEDIATRICS
LA English
DT Article
ID NATIONAL PROBABILITY SAMPLES; LOW-PREVALENCE DISEASES; SERVICES
UTILIZATION; HIV COST; CHILDRENS
AB OBJECTIVE: In 2010, the National Children's Study launched 3 alternative recruitment methods to test possible improvements in efficiency compared with traditional household-based recruitment and participant enrollment. In 2012, a fourth method, provider-based sampling (PBS), tested a probability-based sampling of prenatal provider locations supplemented by a second cohort of neonates born at a convenience sample of maternity hospitals.
METHODS: From a sampling frame of 472 prenatal care provider locations and 59 maternity hospitals, 49 provider and 7 hospital locations within or just outside 3 counties participated in study recruitment. During first prenatal care visits or immediately postdelivery at these locations, face-to-face contact was used to screen and recruit eligible women.
RESULTS: Of 1450 screened women, 1270 were eligible. Consent rates at prenatal provider locations (62%-74% by county) were similar to those at birth locations (64%-77% by county). During 6 field months, 3 study centers enrolled a total prenatal cohort of 530 women (the majority in the first trimester) and during 2 months enrolled a birth cohort of an additional 320 mother-newborn dyads. As personnel became experienced in the field, the time required to enroll a woman in the prenatal cohort declined from up to 200 hours to 50 to 100 hours per woman recruited.
CONCLUSIONS: We demonstrated that PBS was feasible and operationally efficient in recruiting a representative cohort of newborns from 3 diverse US counties. Our findings suggest that PBS is a practical approach to recruit large pregnancy and birth cohorts across the United States.
C1 [McLaughlin, Thomas J.; Aupont, Onesky; Moore-Simas, Tiffany A.; Sepavich, Deidre; Felice, Marianne] Univ Massachusetts, Worcester, MA 01605 USA.
[Kozinetz, Claudia A.] East Tennessee State Univ, Johnson City, TN USA.
[Hubble, David] Westat Corp, Rockville, MD USA.
[Davis, Deborah] Univ Louisville, Louisville, KY 40292 USA.
[Park, Christina; Brenner, Ruth] NICHHD, Rockville, MD USA.
[Caviness, Chantal] Baylor Coll Med, Houston, TX 77030 USA.
[Downs, Tim] Clark Univ, Worcester, MA 01610 USA.
[Selwyn, Beatrice J.] Univ Texas Sch Publ Hlth, Houston, TX USA.
[Forman, Michele R.] Univ Texas Austin, Austin, TX 78712 USA.
RP McLaughlin, TJ (reprint author), Univ Massachusetts, Dept Pediat, Sch Med, 222 Maple Ave, Shrewsbury, MA 01545 USA.
EM thomas.mclaughlin@umassmed.edu
FU National Institute for Child Health and Human Development
[HHSN275200800020C, HHSC275200800006C, HHSN267200700024C]; National
Institutes of Health (NIH)
FX Supported in part by National Institute for Child Health and Human
Development Contracts HHSN275200800020C, HHSC275200800006C, and
HHSN267200700024C. Funded by the National Institutes of Health (NIH).
NR 9
TC 0
Z9 0
U1 1
U2 1
PU AMER ACAD PEDIATRICS
PI ELK GROVE VILLAGE
PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA
SN 0031-4005
EI 1098-4275
J9 PEDIATRICS
JI Pediatrics
PD JUN
PY 2016
VL 137
SU 4
AR e20154410F
DI 10.1542/peds.2015-4410F
PG 10
WC Pediatrics
SC Pediatrics
GA EE2KQ
UT WOS:000389413300006
PM 27251871
ER
PT J
AU Kamp, WM
Wang, PY
Hwang, PM
AF Kamp, William M.
Wang, Ping-yuan
Hwang, Paul M.
TI TP53 mutation, mitochondria and cancer
SO CURRENT OPINION IN GENETICS & DEVELOPMENT
LA English
DT Article
ID LI-FRAUMENI-SYNDROME; TUMOR-SUPPRESSOR P53; MUTANT P53; BREAST-CANCER;
METABOLIC-REGULATION; GLUCOSE-METABOLISM; RECEPTOR PROMOTER;
PANCREATIC-CANCER; FAMILIAL SYNDROME; OXIDATIVE STRESS
AB Under normal conditions, basal levels of wild-type p53 promote mitochondrial function through multiple mechanisms. Remarkably, some missense mutations of p53, in contrast to the null state, can result in the retention of its metabolic activities. These effects are particularly prominent in the mitochondria and demonstrate a functional role for mutant p53 in cancer metabolism. This review summarizes accumulating data on the mechanisms by which p53 missense mutations can regulate mitochondrial metabolism and promote the viability and survival of both normal and cancer cells, thus acting as a double edged sword for the host. Greater understanding of these mechanisms may provide insights for developing new treatment or preventive strategies against cancer.
C1 [Kamp, William M.; Wang, Ping-yuan; Hwang, Paul M.] NHLBI, Ctr Mol Med, NIH, Bldg 10, Bethesda, MD 20892 USA.
RP Hwang, PM (reprint author), NHLBI, Ctr Mol Med, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM hwangp@mail.nih.gov
FU intramural program of National Heart, Lung and Blood Institute (NHLBI),
NIH
FX We wish to thank Jie (Jerry) Li for assistance with the artwork and
other members of our laboratory Ju-Gyeong Kang, Ji-Hoon Park, and Jie
Zhuang for helpful discussions and critical review of the manuscript.
This work was supported by the intramural program of National Heart,
Lung and Blood Institute (NHLBI), NIH.
NR 85
TC 6
Z9 6
U1 0
U2 0
PU CURRENT BIOLOGY LTD
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 0959-437X
EI 1879-0380
J9 CURR OPIN GENET DEV
JI Curr. Opin. Genet. Dev.
PD JUN
PY 2016
VL 38
BP 16
EP 22
DI 10.1016/j.gde.2016.02.007
PG 7
WC Cell Biology; Genetics & Heredity
SC Cell Biology; Genetics & Heredity
GA EA6LH
UT WOS:000386740200004
PM 27003724
ER
PT J
AU Rouault, TA
AF Rouault, Tracey A.
TI Mitochondrial iron overload: causes and consequences
SO CURRENT OPINION IN GENETICS & DEVELOPMENT
LA English
DT Article
ID SIDEROBLASTIC ANEMIA-MLASA; SULFUR CLUSTER BIOGENESIS; RESPIRATORY
COMPLEX I; FE-S CLUSTERS; LACTIC-ACIDOSIS; FRIEDREICHS-ATAXIA; CAUSES
MYOPATHY; INTERACTING PROTEIN; RING SIDEROBLASTS; ASSEMBLY COMPLEX
AB Pathological overload of iron in the mitochondrial matrix has been observed in numerous diseases, including sideroblastic anemias, which have many causes, and in genetic diseases that affect iron-sulfur cluster biogenesis, heme synthesis, and mitochondrial protein translation and its products. Although high expression of the mitochondrial iron importer, mitoferrin, appears to be an underlying common feature, it is unclear what drives high mitoferrin expression and what other proteins are involved in trapping excess toxic iron in the mitochondrial matrix. Numerous examples of human diseases and model systems suggest that mitochondrial iron homeostasis is coordinated through transcriptional remodeling. A cytosolic/nuclear molecule may affect a transcriptional factor to coordinate the events that lead to iron accumulation, but no candidates for this role have yet been identified.
C1 [Rouault, Tracey A.] NICHHD, Eunice Kennedy Shriver, Bethesda, MD 20892 USA.
RP Rouault, TA (reprint author), NICHHD, Eunice Kennedy Shriver, Bethesda, MD 20892 USA.
EM Rouault@mail.nih.gov
FU intramural program of NICHD
FX The author thanks the intramural program of NICHD for support, and
members of the Rouault lab for their help with this mini-review.
NR 73
TC 2
Z9 3
U1 3
U2 3
PU CURRENT BIOLOGY LTD
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 0959-437X
EI 1879-0380
J9 CURR OPIN GENET DEV
JI Curr. Opin. Genet. Dev.
PD JUN
PY 2016
VL 38
BP 31
EP 37
DI 10.1016/j.gde.2016.02.004
PG 7
WC Cell Biology; Genetics & Heredity
SC Cell Biology; Genetics & Heredity
GA EA6LH
UT WOS:000386740200006
PM 27026139
ER
PT J
AU Young, MJ
Copeland, WC
AF Young, Matthew J.
Copeland, William C.
TI Human mitochondrial DNA replication machinery and disease
SO CURRENT OPINION IN GENETICS & DEVELOPMENT
LA English
DT Article
ID PROGRESSIVE EXTERNAL OPHTHALMOPLEGIA; STRUCTURE-FUNCTION DEFECTS;
RECESSIVE TWINKLE MUTATIONS; POLYMERASE GAMMA-SUBUNITS; IMPAIR MTDNA
REPLICATION; MULTIPLE DELETIONS; ACCESSORY SUBUNIT; HELICASE TWINKLE;
MAMMALIAN EMBRYOGENESIS; RNA-POLYMERASE
AB The human mitochondrial genome is replicated by DNA polymerase gamma in concert with key components of the mitochondrial DNA (mtDNA) replication machinery. Defects in mtDNA replication or nucleotide metabolism cause deletions, point mutations, or depletion of mtDNA. The resulting loss of cellular respiration ultimately induces mitochondrial genetic diseases, including mtDNA depletion syndromes (MDS) such as Alpers or early infantile hepatocerebral syndromes, and mtDNA deletion disorders such as progressive external ophthalmoplegia, ataxia-neuropathy, or mitochondrial neurogastrointestinal encephalomyopathy. Here we review the current literature regarding human mtDNA replication and heritable disorders caused by genetic changes of the POLG, POLG2, Twinkle, RNASEH1, DNA2, and MGME1 genes.
C1 [Young, Matthew J.; Copeland, William C.] NIEHS, Genome Integr & Struct Biol Lab, POB 12233, Res Triangle Pk, NC 27709 USA.
[Young, Matthew J.] Southern Illinois Univ, Dept Biochem & Mol Biol, Sch Med, Carbondale, IL 62901 USA.
RP Copeland, WC (reprint author), NIEHS, Genome Integr & Struct Biol Lab, POB 12233, Res Triangle Pk, NC 27709 USA.
EM copelan1@niehs.nih.gov
FU Intramural Research Program of the NIH, National Institute of
Environmental Health Sciences [ES 065078, ES 065080]; NIH Pathway to
Independence Award [1K99ES022638-01]
FX This research was supported by the Intramural Research Program of the
NIH, National Institute of Environmental Health Sciences (ES 065078 and
ES 065080 to WCC) and by a NIH Pathway to Independence Award to MJY
(1K99ES022638-01).
NR 88
TC 4
Z9 4
U1 0
U2 0
PU CURRENT BIOLOGY LTD
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 0959-437X
EI 1879-0380
J9 CURR OPIN GENET DEV
JI Curr. Opin. Genet. Dev.
PD JUN
PY 2016
VL 38
BP 52
EP 62
DI 10.1016/j.gde.2016.03.005
PG 11
WC Cell Biology; Genetics & Heredity
SC Cell Biology; Genetics & Heredity
GA EA6LH
UT WOS:000386740200009
PM 27065468
ER
PT J
AU Simonsick, EM
Glynn, NW
Jerome, GJ
Shardell, M
Schrack, JA
Ferrucci, L
AF Simonsick, Eleanor M.
Glynn, Nancy W.
Jerome, Gerald J.
Shardell, Michelle
Schrack, Jennifer A.
Ferrucci, Luigi
TI Fatigued, but Not Frail: Perceived Fatigability as a Marker of Impending
Decline in Mobility-Intact Older Adults
SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY
LA English
DT Article
DE fatigability; mobility decline; aging
ID PHYSICAL PERFORMANCE-MEASURES; GAIT SPEED; VITAL EXHAUSTION; HEALTH ABC;
DISABILITY; IMPAIRMENT; LIMITATION; INDICATOR; WALKING; RISK
AB OBJECTIVES: To evaluate perceived fatigability as a predictor of meaningful functional decline in non-mobilitylimited older adults.
DESIGN: Longitudinal analysis of data from the Baltimore Longitudinal Study of Aging (BLSA).
SETTING: National Institute on Aging, Clinical Research Unit, Baltimore, Maryland.
PARTICIPANTS: Men and women aged 60 to 89 participating in the BLSA with concurrent perceived fatigability and functional assessments and follow-up functional assessment within 1 to 3 years (N = 540).
MEASUREMENTS: Perceived fatigability was ascertained using the Borg rating of perceived exertion (RPE) after 5 minutes of treadmill walking at 1.5 miles per hour. Functional assessments included usual and fast gait speed, the Health, Aging and Body Composition physical performance battery (HABC PPB) and reported walking ability. Reported tiredness and energy level were examined as complementary predictors. Covariates included age, age squared, race, follow- up time, and baseline function. Meaningful decline was defined as 0.05 m/s per year for usual gait speed, 0.07 m/s per year for fast gait speed, 0.12 points/year for HABC PPB, and 1 point for walking ability index.
RESULTS: Over a mean 2.1 years, 20-31% of participants declined across functional assessments. Fatigability was associated with a 13-19% greater likelihood of meaningful decline in all measures (P =.002-.02) per 1-unit RPE increase. After considering tiredness and energy level separately, findings were essentially unchanged, and neither was associated with gait speed or physical performance decline. In contrast, each separately predicted decline in reported walking ability independent of fatigability (P=.03 and P<.001, respectively).
CONCLUSION: Routine assessment of fatigability may help identify older persons vulnerable to greater-than-expected functional decline.
C1 [Simonsick, Eleanor M.; Shardell, Michelle; Ferrucci, Luigi] NIA, Intramural Res Program, Baltimore, MD 21224 USA.
[Glynn, Nancy W.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA.
[Jerome, Gerald J.] Towson Univ, Coll Hlth Profess, Dept Kinesiol, Towson, MD USA.
[Schrack, Jennifer A.] Johns Hopkins Univ, Dept Epidemiol, Bloomberg Sch Publ Hlth, Baltimore, MD USA.
RP Simonsick, EM (reprint author), 3001 S Hanover St,5th Floor, Baltimore, MD 21225 USA.
EM simonsickel@mail.nih.gov
OI Glynn, Nancy/0000-0003-2265-0162
FU Intramural Research Program, National Institute on Aging, National
Institutes of Health; Intramural Research Program of the National
Institute on Aging
FX Funded by the Intramural Research Program, National Institute on Aging,
National Institutes of Health. The BLSA is supported by the Intramural
Research Program of the National Institute on Aging.
NR 31
TC 2
Z9 2
U1 5
U2 5
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0002-8614
EI 1532-5415
J9 J AM GERIATR SOC
JI J. Am. Geriatr. Soc.
PD JUN
PY 2016
VL 64
IS 6
BP 1287
EP 1292
DI 10.1111/jgs.14138
PG 6
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA DW3MY
UT WOS:000383546900017
PM 27253228
ER
PT J
AU Pitzer, VE
Aguas, R
Riley, S
Loeffen, WLA
Wood, JLN
Grenfell, BT
AF Pitzer, Virginia E.
Aguas, Ricardo
Riley, Steven
Loeffen, Willie L. A.
Wood, James L. N.
Grenfell, Bryan T.
TI High turnover drives prolonged persistence of influenza in managed pig
herds
SO JOURNAL OF THE ROYAL SOCIETY INTERFACE
LA English
DT Article
DE influenza; swine; surveillance; mathematical modelling; transmission
dynamics
ID RESPIRATORY SYNDROME VIRUS; H1N1 2009 VIRUS; A VIRUS; UNITED-STATES;
TRANSMISSION DYNAMICS; POPULATION-DYNAMICS; GLOBAL CIRCULATION; MEASLES
EPIDEMICS; COMMUNITY SIZE; FADE-OUT
AB Pigs have long been hypothesized to play a central role in the emergence of novel human influenza A virus (IAV) strains, by serving as mixing vessels for mammalian and avian variants. However, the key issue of viral persistence in swine populations at different scales is ill understood. We address this gap using epidemiological models calibrated against seroprevalence data from Dutch finishing pigs to estimate the 'critical herd size' (CHS) for IAV persistence. We then examine the viral phylogenetic evidence for persistence by comparing human and swine IAV. Models suggest a CHS of approximately 3000 pigs above which influenza was likely to persist, i.e. orders of magnitude lower than persistence thresholds for IAV and other acute viruses in humans. At national and regional scales, we found much stronger empirical signatures of prolonged persistence of IAV in swine compared with human populations. These striking levels of persistence in small populations are driven by the high recruitment rate of susceptible piglets, and have significant implications for management of swine and for overall patterns of genetic diversity of IAV.
C1 [Pitzer, Virginia E.] Yale Univ, Yale Sch Publ Hlth, Dept Epidemiol Microbial Dis, New Haven, CT 06520 USA.
[Pitzer, Virginia E.; Grenfell, Bryan T.] NIH, Fogarty Int Ctr, Rockville, MD 20850 USA.
[Aguas, Ricardo; Riley, Steven] Imperial Coll, Sch Publ Hlth, Dept Infect Dis Epidemiol, MRC Ctr Outbreak Anal & Modelling, London SW7 2AZ, England.
[Loeffen, Willie L. A.] Cent Vet Inst, Dept Virol, NL-8200 AB Lelystad, Netherlands.
[Wood, James L. N.] Univ Cambridge, Dept Vet Med, Dis Dynam Unit, Cambridge CB3 0ES, England.
[Grenfell, Bryan T.] Princeton Univ, Dept Ecol & Evolutionary Biol, Princeton, NJ 08544 USA.
RP Pitzer, VE (reprint author), Yale Univ, Yale Sch Publ Hlth, Dept Epidemiol Microbial Dis, New Haven, CT 06520 USA.; Pitzer, VE (reprint author), NIH, Fogarty Int Ctr, Rockville, MD 20850 USA.
EM virginia.pitzer@yale.edu
FU RAPIDD program of the Science and Technology Directorate; Department of
Homeland Security; Fogarty International Center, National Institutes of
Health; Bill & Melinda Gates Foundation; Alborada Trust; European Union
FP7 project ANTIGONE [278976]; BBSRC sLOLA [BB/L001330/1]
FX This work was supported by the RAPIDD program of the Science and
Technology Directorate, Department of Homeland Security, and the Fogarty
International Center, National Institutes of Health (V.E.P., S.R.,
J.L.N.W. and B.T.G.) and the Bill & Melinda Gates Foundation (V.E.P. and
B.T.G.). J.L.N.W. is also supported by the Alborada Trust, the European
Union FP7 project ANTIGONE (contract no. 278976) and by BBSRC sLOLA
BB/L001330/1.
NR 51
TC 1
Z9 1
U1 0
U2 0
PU ROYAL SOC
PI LONDON
PA 6-9 CARLTON HOUSE TERRACE, LONDON SW1Y 5AG, ENGLAND
SN 1742-5689
EI 1742-5662
J9 J R SOC INTERFACE
JI J. R. Soc. Interface
PD JUN 1
PY 2016
VL 13
IS 119
AR 20160138
DI 10.1098/rsif.2016.0138
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EA6FP
UT WOS:000386722200006
ER
PT J
AU Journy, N
Morton, LM
Kleinerman, RA
Bekelman, JE
de Gonzalez, AB
AF Journy, N.
Morton, L. -M.
Kleinerman, R. -A.
Bekelman, J. -E.
de Gonzalez, A. Berrington
TI Intensity-modulated radiation therapy in the treatment of localized
prostate cancers and risk of second cancers
SO BULLETIN DU CANCER
LA French
DT Meeting Abstract
C1 [Journy, N.; Morton, L. -M.; Kleinerman, R. -A.; de Gonzalez, A. Berrington] NCI, Rockville, MD USA.
[Bekelman, J. -E.] Univ Penn, Dept Radiat Oncol, Perelman Sch Med,Leonard Davis Inst Hlth Econ,Abr, Ctr Clin Epidemiol & Biostat,Dept Biostat & Epide, Philadelphia, PA 19104 USA.
EM njourny@netcourrier.com
NR 0
TC 0
Z9 0
U1 0
U2 0
PU JOHN LIBBEY EUROTEXT LTD
PI MONTROUGE
PA 127 AVE DE LA REPUBLIQUE, 92120 MONTROUGE, FRANCE
SN 0007-4551
EI 1769-6917
J9 B CANCER
JI Bull. Cancer
PD JUN
PY 2016
VL 103
IS 6
SU 1
MA PC- 03
BP S114
EP S114
PG 1
WC Oncology
SC Oncology
GA ED3DK
UT WOS:000388729300026
ER
PT J
AU de la Hoya, M
Soukarieh, O
Lopez-Perolio, I
Vega, A
Walker, LC
van Ierland, Y
Baralle, D
Santamarina, M
Lattimore, V
Wijnen, J
Whiley, P
Blanco, A
Raponi, M
Hauke, J
Wappenschmidt, B
Becker, A
Hansen, TVO
Behar, R
Niederacher, D
Arnold, N
Dworniczak, B
Steinemann, D
Faust, U
Rubinstein, W
Hulick, PJ
Houdayer, C
Caputo, SM
Castera, L
Pesaran, T
Chao, E
Brewer, C
Southey, MC
van Asperen, CJ
Singer, CF
Sullivan, J
Poplawski, N
Mai, P
Peto, J
Johnson, N
Burwinkel, B
Surowy, H
Bojesen, SE
Flyger, H
Lindblom, A
Margolin, S
Chang-Claude, J
Rudolph, A
Radice, P
Galastri, L
Olson, JE
Hallberg, E
Giles, G
Milne, RL
Andrulis, IL
Glendon, G
Hall, P
Czene, K
Blows, F
Shah, M
Wang, Q
Dennis, J
Michailidou, K
McGuffog, L
Bolla, MK
Antoniou, AC
Easton, DF
Couch, FJ
Tavtigian, S
Vreeswijk, MP
Parsons, M
Meeks, HD
Martins, A
Goldgar, DE
Spurdle, AB
AF de la Hoya, Miguel
Soukarieh, Omar
Lopez-Perolio, Irene
Vega, Ana
Walker, Logan C.
van Ierland, Yvette
Baralle, Diana
Santamarina, Marta
Lattimore, Vanessa
Wijnen, Juul
Whiley, Philip
Blanco, Ana
Raponi, Michela
Hauke, Jan
Wappenschmidt, Barbara
Becker, Alexandra
Hansen, Thomas V. O.
Behar, Raquel
Niederacher, Diether
Arnold, Norbert
Dworniczak, Bernd
Steinemann, Doris
Faust, Ulrike
Rubinstein, Wendy
Hulick, Peter J.
Houdayer, Claude
Caputo, Sandrine M.
Castera, Laurent
Pesaran, Tina
Chao, Elizabeth
Brewer, Carole
Southey, Melissa C.
van Asperen, Christi J.
Singer, Christian F.
Sullivan, Jan
Poplawski, Nicola
Phuong Mai
Peto, Julian
Johnson, Nichola
Burwinkel, Barbara
Surowy, Harald
Bojesen, Stig E.
Flyger, Henrik
Lindblom, Annika
Margolin, Sara
Chang-Claude, Jenny
Rudolph, Anja
Radice, Paolo
Galastri, Laura
Olson, Janet E.
Hallberg, Emily
Giles, GrahamG.
Milne, Roger L.
Andrulis, Irene L.
Glendon, Gord
Hall, Per
Czene, Kamila
Blows, Fiona
Shah, Mitul
Wang, Qin
Dennis, Joe
Michailidou, Kyriaki
McGuffog, Lesley
Bolla, Manjeet K.
Antoniou, Antonis C.
Easton, Douglas F.
Couch, Fergus J.
Tavtigian, Sean
Vreeswijk, Maaike P.
Parsons, Michael
Meeks, Huong D.
Martins, Alexandra
Goldgar, David E.
Spurdle, Amanda B.
CA KConFaB Investigators
TI Combined genetic and splicing analysis of BRCA1 c.[594-2A > C; 641A > G]
highlights the relevance of naturally occurring in-frame transcripts for
developing disease gene variant classification algorithms
SO HUMAN MOLECULAR GENETICS
LA English
DT Article
ID SEQUENCE VARIANTS; CLINICAL-SIGNIFICANCE; ASSAY; GUIDELINES; PROTEIN;
BREAST; SITE
AB We confirm that BRCA1c.[594-2A > C;641A > G] should not be considered a high-risk pathogenic variant. Importantly, results from our detailed mRNA analysis suggest that BRCA-associated cancer risk is likely not markedly increased for individuals who carry a truncating variant in BRCA1 exons 9 or 10, or any other BRCA1 allele that permits 20-30% of tumor suppressor function. More generally, our findings highlight the importance of assessing naturally occurring alternative splicing for clinical evaluation of variants in disease-causing genes.
C1 [de la Hoya, Miguel; Lopez-Perolio, Irene; Behar, Raquel] Hosp Clin San Carlos, IdISSC, Mol Oncol Lab, C Martin Lagos S-N, Madrid 28040, Spain.
[Soukarieh, Omar; Martins, Alexandra] Univ Rouen, Normandy Ctr Genom & Personalized Med, INSERM, U1079,IRIB, Rouen, France.
[Vega, Ana; Blanco, Ana] USC, Fdn Publ Galega Med Xenom SERGAS, Grp Med Xenom, IDIS,CIBERER, Santiago De Compostela 15706, Spain.
[Walker, Logan C.; Lattimore, Vanessa] Univ Otago, Dept Pathol, Christchurch 8140, New Zealand.
[van Ierland, Yvette; Wijnen, Juul; van Asperen, Christi J.; Vreeswijk, Maaike P.] Leiden Univ, Dept Clin Genet, Med Ctr, NL-2300 Leiden, Netherlands.
[Baralle, Diana; Raponi, Michela] Univ Southampton, Human Dev & Hlth, Fac Med, Southampton SO16 5YA, Hants, England.
[Santamarina, Marta] Univ Santiago de Compostela, CIBERER, Grp Med Xenom, Fdn Galega Med Xenom SERGAS, Santiago De Compostela 15706, Spain.
[Wijnen, Juul] Leiden Univ, Dept Clin Genet, Med Ctr, NL-2300 Leiden, Netherlands.
[Whiley, Philip; Parsons, Michael; Spurdle, Amanda B.] QIMR Berghofer Med Res Inst, Dept Genet & Computat Biol, Brisbane, Qld 4006, Australia.
[Hauke, Jan; Wappenschmidt, Barbara; Becker, Alexandra] Univ Hosptial Cologne, Fac Med, Ctr Integrated Oncol CIO, Ctr Hereditary Breast & Ovarian Canc, D-50931 Cologne, Germany.
[Hansen, Thomas V. O.] Copenhagen Univ Hosp, Rigshosp, Ctr Genom Med, DK-2100 Copenhagen, Denmark.
[KConFaB Investigators] Univ Melbourne, Peter MacCallum Canc Ctr, Melbourne, Vic 3002, Australia.
[Niederacher, Diether] Univ Dusseldorf, Univ Hosp Dusseldorf, Dept Gynaecol & Obstet, D-40225 Dusseldorf, Germany.
[Arnold, Norbert] Univ Kiel, Dept Gynaecol & Obstet, Univ Hosp Schleswig Holstein, Campus Kiel, D-24105 Kiel, Germany.
[Dworniczak, Bernd] Univ Munster, Inst Human Genet, D-48149 Munster, Germany.
[Steinemann, Doris] Hannover Med Sch, Inst Human Genet, D-30625 Hannover, Germany.
[Faust, Ulrike] Univ Tubingen Hosp, Inst Med Genet & Appl Genom, D-72076 Tubingen, Germany.
[Rubinstein, Wendy] NIH, Bldg 10, Bethesda, MD 20892 USA.
[Hulick, Peter J.] Univ Chicago, NorthShore Univ Hlth Syst, Pritzker Sch Med, Ctr Med Genet, Evanston, IL 60201 USA.
[Houdayer, Claude] Inst Curie, Dept Biol Tumeurs, Serv Genet, Paris, France.
[Houdayer, Claude] Inst Curie, Ctr Rech, INSERM, U830, Paris, France.
[Houdayer, Claude] Univ Paris 05, Sorbonne Paris Cite, F-75248 Paris, France.
[Caputo, Sandrine M.] Inst Curie, Dept Biol Tumeurs, Serv Genet, F-75248 Paris, France.
[Castera, Laurent] Ctr Francois Baclesse, Lab Biol & Genet Canc, F-14076 Caen, France.
[Pesaran, Tina; Chao, Elizabeth] Ambry Genet, Aliso Viejo, CA 92656 USA.
[Brewer, Carole] Royal Devon & Exeter Hosp, Dept Clin Genet, Exeter, Devon, England.
[Southey, Melissa C.] Univ Melbourne, Dept Pathol, Genet Epidemiol Lab, Melbourne, Vic 3010, Australia.
[Singer, Christian F.] Med Univ Vienna, Dept Obstet & Gynaecol, Waehringer Guertel 18-20, A-1090 Vienna, Austria.
[Sullivan, Jan] Christchurch Hosp, Genet Hlth Serv NZ, South Isl Hub, Christchurch 8140, New Zealand.
[Poplawski, Nicola] Womens & Childrens Hosp, SA Pathol, South Australian Clin Genet Serv, Adult Genet Unit, Adelaide, SA 5067, Australia.
[Poplawski, Nicola] Univ Adelaide, Univ Dept Paediat, North Terrace, Adelaide, SA 5000, Australia.
[Phuong Mai] NCI, Clin Genet Branch, DCEG, NIH, Bethesda, MD 20892 USA.
[Peto, Julian] London Sch Hyg & Trop Med, London WC1E 7HT, England.
[Johnson, Nichola] Inst Canc Res, Breakthrough Breast Canc Res Ctr, London SW3 6JB, England.
[Johnson, Nichola] Inst Canc Res, Div Breast Canc Res, London SW3 6JB, England.
[Burwinkel, Barbara; Surowy, Harald] Heidelberg Univ, Dept Gynecol & Obstet, Mol Biol Breast Canc, D-69120 Heidelberg, Germany.
[Burwinkel, Barbara; Surowy, Harald] DKFZ, Mol Epidemiol Grp, German Canc Res Ctr, D-69120 Heidelberg, Germany.
[Bojesen, Stig E.] Herlev & Gentofte Hosp, Copenhagen Gen Populat Study, DK-2730 Copenhagen, Denmark.
[Bojesen, Stig E.] Copenhagen Univ Hosp, Herlev Hosp, Dept Clin Biochem, DK-2730 Herlev, Denmark.
[Bojesen, Stig E.] Univ Copenhagen, Fac Hlth & Med Sci, DK-1165 Copenhagen, Denmark.
[Flyger, Henrik] Copenhagen Univ Hosp, Herlev & Gentofte Hosp, Dept Breast Surg, DK-2730 Herlev, Denmark.
[Lindblom, Annika] Karolinska Inst, Dept Mol Med & Surg, SE-17177 Stockholm, Sweden.
[Margolin, Sara] Karolinska Inst, Dept Oncol Pathol, SE-17177 Stockholm, Sweden.
[Chang-Claude, Jenny; Rudolph, Anja] German Canc Res Ctr, Div Canc Epidemiol, D-69120 Heidelberg, Germany.
[Chang-Claude, Jenny] Univ Med Ctr Hamburg Eppendorf, UCCH, D-20246 Hamburg, Germany.
[Radice, Paolo] Fdn IRCCS Ist Nazl Tumori, Dept Prevent & Predict Med, Unit Mol Bases Genet Risk & Genet Testing, I-20139 Milan, Italy.
[Galastri, Laura] Assoc Volontari Italiani Sangue AVIS Comunale Mil, I-20139 Milan, Italy.
[Olson, Janet E.; Hallberg, Emily; Couch, Fergus J.] Mayo Clin, Dept Hlth Sci Res, Rochester, MN 55905 USA.
[Giles, GrahamG.; Milne, Roger L.] Univ Melbourne, Ctr Epidemiol & Biostat, Melbourne Sch Populat & Global Hlth, Melbourne, Vic 3010, Australia.
[Giles, GrahamG.; Milne, Roger L.] Canc Council Victoria, Canc Epidemiol Ctr, Melbourne, Vic 3004, Australia.
[Andrulis, Irene L.; Glendon, Gord] Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, Toronto, ON M5G 1X5, Canada.
[Andrulis, Irene L.] Univ Toronto, Dept Mol Genet, Toronto, ON M5B 1W8, Canada.
[Hall, Per; Czene, Kamila] Karolinska Inst, Dept Med Epidemiol & Biostat, SE-17177 Stockholm, Sweden.
[Blows, Fiona; Shah, Mitul] Univ Cambridge, Dept Oncol, Ctr Canc Genet Epidemiol, Cambridge CB1 8RN, England.
[Wang, Qin; Dennis, Joe; Michailidou, Kyriaki; McGuffog, Lesley; Bolla, Manjeet K.; Antoniou, Antonis C.; Easton, Douglas F.] Univ Cambridge, Dept Publ Hlth & Primary Care, Ctr Canc Genet Epidemiol, Cambridge CB1 8RN, England.
[Michailidou, Kyriaki] Cyprus Inst Neurol & Genet, Dept Electron Microscopy Mol Pathol, CY-1683 Nicosia, Cyprus.
[Couch, Fergus J.] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN 55905 USA.
[Tavtigian, Sean; Meeks, Huong D.] Univ Utah, Sch Med, Huntsman Canc Inst, Dept Oncol Sci, Salt Lake City, UT 84132 USA.
[Goldgar, David E.] Univ Utah, Sch Med, Huntsman Canc Inst, Dept Dermatol, Salt Lake City, UT 84132 USA.
RP de la Hoya, M (reprint author), Hosp Clin San Carlos, IdISSC, Mol Oncol Lab, C Martin Lagos S-N, Madrid 28040, Spain.; Spurdle, AB (reprint author), QIMR Berghofer Med Res Inst, 300 Herston Rd, Brisbane, Qld 4006, Australia.
EM mhoya@hotmail.com; amanda.spurdle@qimr.edu.au
RI Arnold, Norbert/E-3012-2010
OI Arnold, Norbert/0000-0003-4523-8808
FU Spanish Instituto de Salud Carlos III - European Regional Development
FEDER Funds [PI12/00539, PI15/00059, PI13/02030]; French Ministry of
Higher Education and Research; University of Otago; Mackenzie Charitable
Foundation; Health Research Council of New Zealand; UK Higher Education
Funding Council; University of Southampton; Cancer research UK;
FamilienHede Nielsen Foundation; Cancer Research-UK; National Institute
of Health [CA128978, CA11616]; NIH [CA128978, P50 CA116201]; US Breast
Cancer Research Foundation; French National Cancer Institute; Direction
Generale de l'Offre des Soins (INCa-DGOS AAP/CFB/CI); French North-West
Canceropole (CNO); Cancer Council Queensland [APP1086286]; NHMRC
[1061779, 1010719]; National Breast Cancer Foundation; National Health
and Medical Research Council; Queensland Cancer Fund; Cancer Council of
New South Wales; Cancer Council of Victoria; Cancer Council of Tasmania;
Cancer Council of South Australia; Cancer Foundation of Western
Australia; German Cancer Aid [109076]; Center for Molecular Medicine
Cologne (CMMC); Cancer Research UK [C1287/A10118, C1287/A11990, C1287/A
10710, C12292/A11174, C1281/A12014, C5047/A8384, C5047/A15007,
C5047/A10692, C1287/A12014]; National Cancer Institute [UM1 CA164920];
Breast Cancer Campaign forming Breast Cancer Now; NHS; Dietmar-Hopp
Foundation; Helmholtz Society; German Cancer Research Center (DKFZ);
Chief Physician Johan Boserup and LiseBoserup Fund; Danish Medical
Research Council; Herlev Hospital; Stockholm City Council;
KarolinskaInstitutet; Stockholm Cancer Foundation; Swedish Cancer
Society; Deutsche Krebshilfee.V. [70-2892-BR I]; Hamburg Cancer Society;
German Cancer Research Center; Federal Ministry of Education and
Research (BMBF) Germany [01KH0402]; Italian Association for Cancer
Research (AIRC); Specialized Program of Research Excellence (SPORE) in
Breast Cancer [CA116201]; Breast Cancer Research Foundation; VicHealth;
Cancer Council Victoria; Australian NHMRC [209057, 251553, 504711];
Marit and Hans Rausings Initiative Against Breast Cancer; Swedish
Medical Research Counsel; CRUK [A490/A11021, C490/A16561]; European
Community [223175 (HEALTH-F2-2009-223175), 223175,
HEALTH-F2-2009-223175]; National Institutes of Health [CA128978];
Post-Cancer GWAS initiative [1U19 CA148537, 1U19 CA148065, 1U19
CA148112]; Department of Defence [W81XWH-10-1-0341]; Canadian Institutes
of Health Research (CIHR) for the CIHR Team in Familial Risks of Breast
Cancer; Komen Foundation for the Cure; Ovarian Cancer Research Fund;
Cancer Research-UK [C1287/A10118, C12292/A11174]
FX The research described was supported by Spanish Instituto de Salud
Carlos III funding, an initiative of the Spanish Ministry of Economy and
Innovation partially supported by European Regional Development FEDER
Funds [PI12/00539 and PI15/00059 to M.d.H., PI13/02030 to A.V.]; the
French Ministry of Higher Education and Research [to O.S.]; the
University of Otago, Mackenzie Charitable Foundation, Maria Lupton, and
.Health Research Council of New Zealand [to L.W.]; UK Higher Education
Funding Council Senior Fellowship Scheme, the University of Southampton
[to D.B.]; Cancer research UK [to D.B., M.R.]; FamilienHede Nielsen
Foundation fund [to T.V.O.H.]; Cancer Research-UK Senior Cancer Research
Fellowship [to A.C.A.]; National Institute of Health [CA128978 and
CA11616 to F.J.C.]; an NIH specialized program of research excellence in
breast cancer to the Mayo Clinic [P50 CA116201 to F.J.C.]; and the US
Breast Cancer Research Foundation [to F.J.C.]; translational grant from
the French National Cancer Institute and Direction Generale de l'Offre
des Soins (INCa-DGOS AAP/CFB/CI) and a grant from the French North-West
Canceropole (CNO) [to A.M.]; The Cancer Council Queensland [APP1086286
to A.B.S.]; the NHMRC Senior Research Fellowship Scheme [ID 1061779 to
A.B.S.]; NHMRC Project grant scheme [ID 1010719 to A.B.S.].; Additional
infrastructure support to consortium members is as follows: kConFab
infrastructure has been supported by funding from the National Breast
Cancer Foundation, National Health and Medical Research Council, the
Queensland Cancer Fund, the Cancer Councils of New South Wales,
Victoria, Tasmania and South Australia, and the Cancer Foundation of
Western Australia [to kConFab, and the kConFab Clinical Follow-up
study].; The German Consortium of Hereditary Breast and Ovarian Cancer
(GC-HBOC) is supported by the German Cancer Aid (grant no 109076, Rita
K. Schmutzler) and by the Center for Molecular Medicine Cologne (CMMC);
The French consortium is supported by the French National Cancer
Institute.; EMBRACE is supported by Cancer Research UK Grants
C1287/A10118 and C1287/A11990.; BCFR was supported by grant UM1 CA164920
from the National Cancer Institute. The content of this manuscript does
not necessarily reflect the views or policies of the National Cancer
Institute or any of the collaborating centers in the Breast Cancer
Family Registry (BCFR), nor does mention of trade names, commercial
products, or organizations imply endorsement by the US Government or the
BCFR.; The BBCS is funded by Cancer Research UK and Breakthrough Breast
Cancer (recently merged with Breast Cancer Campaign forming Breast
Cancer Now) and acknowledges NHS funding to the NIHR Biomedical Research
Centre, and the National Cancer Research Network (NCRN).; The BSUCH
study was supported by the Dietmar-Hopp Foundation, the Helmholtz
Society and the German Cancer Research Center (DKFZ).; The CGPS was
supported by the Chief Physician Johan Boserup and LiseBoserup Fund, the
Danish Medical Research Council and Herlev Hospital; KARBAC was
supported financially through the regional agreement on medical training
and clinical research (ALF) between Stockholm City Council and
KarolinskaInstitutet, and from the Stockholm Cancer Foundation and the
Swedish Cancer Society.; The MARIE study was supported by the Deutsche
Krebshilfee.V. [70-2892-BR I], the Hamburg Cancer Society, the German
Cancer Research Center and the Federal Ministry of Education and
Research (BMBF) Germany [01KH0402].; MBCSG is supported by grants from
the Italian Association for Cancer Research (AIRC) and by funds from the
Italian citizens who allocated the 5/1000 share of their tax payment
according to Italian laws in support of the Fondazione IRCCS
IstitutoNazionaleTumori.; The MCBCS was supported by the NIH grant
CA128978 and a Specialized Program of Research Excellence (SPORE) in
Breast Cancer [CA116201], the Breast Cancer Research Foundation and a
generous gift from the David F. and Margaret T. Grohne Family Foundation
and the Ting Tsung and Wei Fong Chao Foundation.; MCCS cohort
recruitment was funded by VicHealth and Cancer Council Victoria. The
MCCS was further supported by Australian NHMRC grants 209057, 251553 and
504711 and by infrastructure provided by Cancer Council Victoria.; OFBCR
was supported by grant UM1 CA164920 from the National Cancer Institute.
The content of this manuscript does not necessarily reflect the views or
policies of the National Cancer Institute or any of the collaborating
centers in the Breast Cancer Family Registry (BCFR), nor does mention of
trade names, commercial products, or organizations imply endorsement by
the US Government or the BCFR.; The pKARMA study was supported by Marit
and Hans Rausings Initiative Against Breast Cancer, and the Swedish
Medical Research Counsel.; SEARCH was supported by grants CRUK
A490/A11021, C490/A16561.; Funding for the iCOGS infrastructure came
from: the European Community's Seventh Framework Programme under grant
agreement no. 223175 (HEALTH-F2-2009-223175) (COGS), Cancer Research UK
(C1287/A10118, C1287/A 10710, C12292/A11174, C1281/A12014, C5047/A8384,
C5047/A15007, C5047/A10692), the National Institutes of Health
(CA128978) and Post-Cancer GWAS initiative (1U19 CA148537, 1U19 CA148065
and 1U19 CA148112 - the GAME-ON initiative), the Department of Defence
(W81XWH-10-1-0341), the Canadian Institutes of Health Research (CIHR)
for the CIHR Team in Familial Risks of Breast Cancer, Komen Foundation
for the Cure, the Breast Cancer Research Foundation and the Ovarian
Cancer Research Fund.; CIMBA data management was supported by Cancer
Research-UK grant C12292/A11174 and C1287/A10118.; BCAC is funded by
Cancer Research UK [C1287/A10118, C1287/A12014] and by the European
Communitys Seventh Framework Programme under grant agreement number
223175 (grant number HEALTH-F2-2009-223175) (COGS).
NR 25
TC 0
Z9 0
U1 6
U2 6
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0964-6906
EI 1460-2083
J9 HUM MOL GENET
JI Hum. Mol. Genet.
PD JUN 1
PY 2016
VL 25
IS 11
BP 2256
EP 2268
DI 10.1093/hmg/ddw094
PG 13
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA ED0TK
UT WOS:000388554700011
PM 27008870
ER
PT J
AU Hansen, MEB
Hunt, SC
Stone, RC
Horvath, K
Herbig, U
Ranciaro, A
Hirbo, J
Beggs, W
Reiner, AP
Wilson, JG
Kimura, M
De Vivo, I
Chen, MM
Kark, JD
Levy, D
Nyambo, T
Tishkoff, SA
Aviv, A
AF Hansen, Matthew E. B.
Hunt, Steven C.
Stone, Rivka C.
Horvath, Kent
Herbig, Utz
Ranciaro, Alessia
Hirbo, Jibril
Beggs, William
Reiner, Alexander P.
Wilson, James G.
Kimura, Masayuki
De Vivo, Immaculata
Chen, Maxine M.
Kark, Jeremy D.
Levy, Daniel
Nyambo, Thomas
Tishkoff, Sarah A.
Aviv, Abraham
TI Shorter telomere length in Europeans than in Africans due to polygenetic
adaptation
SO HUMAN MOLECULAR GENETICS
LA English
DT Article
ID PANCREATIC-CANCER; PRECURSOR LESIONS; PROSTATE-CANCER; BREAST-CANCER;
LUNG-CANCER; MELANOMA; RISK; ASSOCIATION; METAANALYSIS; BIOLOGY
AB Leukocyte telomere length (LTL), which reflects telomere length in other somatic tissues, is a complex genetic trait. Eleven SNPs have been shown in genome-wide association studies to be associated with LTL at a genome-wide level of significance within cohorts of European ancestry. It has been observed that LTL is longer in African Americans than in Europeans. The underlying reason for this difference is unknown. Here we show that LTL is significantly longer in sub-Saharan Africans than in both Europeans and African Americans. Based on the 11 LTL-associated alleles and genetic data in phase 3 of the 1000 Genomes Project, we show that the shifts in allele frequency within Europe and between Europe and Africa do not fit the pattern expected by neutral genetic drift. Our findings suggest that differences in LTL within Europeans and between Europeans and Africans is influenced by polygenic adaptation and that differences in LTL between Europeans and Africans might explain, in part, ethnic differences in risks for human diseases that have been linked to LTL.
C1 [Hansen, Matthew E. B.; Ranciaro, Alessia; Hirbo, Jibril; Beggs, William; Tishkoff, Sarah A.] Univ Penn, Sch Med, Dept Genet, Philadelphia, PA 19104 USA.
[Hansen, Matthew E. B.] Univ Penn, Sch Med, Ctr Excellence Environm Toxicol, Philadelphia, PA 19104 USA.
[Tishkoff, Sarah A.] Univ Penn, Dept Biol, Sch Arts & Sci, Philadelphia, PA 19104 USA.
[Hunt, Steven C.] Weill Cornell Med Coll, Dept Med Genet, Doha, Qatar.
[Hunt, Steven C.] Univ Utah, Sch Med, Cardiovasc Genet Div, Salt Lake City, UT 84108 USA.
[Stone, Rivka C.; Horvath, Kent; Herbig, Utz; Kimura, Masayuki; Aviv, Abraham] Rutgers, New Jersey Med Sch, Ctr Human Dev & Aging, Newark, NJ 07103 USA.
[Reiner, Alexander P.] Univ Washington, Dept Epidemiol, Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA.
[Wilson, James G.] Univ Mississippi, Dept Physiol & Biophys, Jackson, MS 38677 USA.
[De Vivo, Immaculata; Chen, Maxine M.] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Program Genet Epidemiol & Stat Genet, Boston, MA 02115 USA.
[Kark, Jeremy D.] Hebrew Univ Jerusalem, Epidemiol Unit, Hadassah Sch Publ Hlth & Community Med, IL-9112001 Jerusalem, Israel.
[Levy, Daniel] NHLBI, Framingham Heart Study, Framingham, MA 01702 USA.
[Nyambo, Thomas] Muhimbili Univ Hlth & Allied Sci, Dept Biochem, Dar Es Salaam 35091, Tanzania.
RP Aviv, A (reprint author), Univ Med & Dent New Jersey, Ctr Human Dev & Aging, 185 South Orange Ave, Newark, NJ 07103 USA.
EM avivab@njms.rutgers.edu
FU National Institutes of Health [T32ES019851, 5DP1ES022577, 1R01DK104339,
1R01GM113657, R01GM113657, 8DP1ES022577, R01-AG020132, R01-HL116446,
R01CA136533, R01CA184572, R01AG18734]; Center of Excellence for
Environmental Toxicology (CEET) at the University of Pennsylvania;
National Heart Lung Blood Institute [HHSN268201300046C,
HHSN268201300047C, HHSN268201300048C, HHSN268201300049C,
HHSN268201300050C]; National Institute on Minority Health and Health
Disparities
FX M.E.B.H. is supported by National Institutes of Health training grant
T32ES019851 and the Center of Excellence for Environmental Toxicology
(CEET) at the University of Pennsylvania. This research is supported by
National Institutes of Health grants 5DP1ES022577, 1R01DK104339, and
1R01GM113657 to S.A.T., and National Institutes of Health grants
R01GM113657, 8DP1ES022577, R01-AG020132, R01-HL116446, R01CA136533,
R01CA184572, R01AG18734. The Jackson Heart Study is supported by
contracts (HHSN268201300046C, HHSN268201300047C, HHSN268201300048C,
HHSN268201300049C, HHSN268201300050C) from the National Heart Lung Blood
Institute and the National Institute on Minority Health and Health
Disparities.
NR 49
TC 3
Z9 3
U1 1
U2 1
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0964-6906
EI 1460-2083
J9 HUM MOL GENET
JI Hum. Mol. Genet.
PD JUN 1
PY 2016
VL 25
IS 11
BP 2324
EP 2330
DI 10.1093/hmg/ddw070
PG 7
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA ED0TK
UT WOS:000388554700016
PM 26936823
ER
PT J
AU Serrano, KJ
Yu, M
Coa, KI
Collins, LM
Atienza, AA
AF Serrano, Katrina J.
Yu, Mandi
Coa, Kisha I.
Collins, Linda M.
Atienza, Audie A.
TI Mining Health App Data to Find More and Less Successful Weight Loss
Subgroups
SO JOURNAL OF MEDICAL INTERNET RESEARCH
LA English
DT Article
DE weight loss; mobile health; mobile app; data mining; classification
ID PHYSICAL-ACTIVITY; ECONOMIC BURDEN; LOSS TRIAL; OBESITY; CLASSIFICATION;
PROGRAM; INTERVENTIONS; MAINTENANCE; OVERWEIGHT; REGRESSION
AB Background: More than half of all smartphone app downloads involve weight, diet, and exercise. If successful, these lifestyle apps may have far-reaching effects for disease prevention and health cost-savings, but few researchers have analyzed data from these apps.
Objective: The purposes of this study were to analyze data from a commercial health app (Lose It!) in order to identify successful weight loss subgroups via exploratory analyses and to verify the stability of the results.
Methods: Cross-sectional, de-identified data from Lose It! were analyzed. This dataset (n=12,427,196) was randomly split into 24 subsamples, and this study used 3 subsamples (combined n=972,687). Classification and regression tree methods were used to explore groupings of weight loss with one subsample, with descriptive analyses to examine other group characteristics. Data mining validation methods were conducted with 2 additional subsamples.
Results: In subsample 1, 14.96% of users lost 5% or more of their starting body weight. Classification and regression tree analysis identified 3 distinct subgroups: "the occasional users" had the lowest proportion (4.87%) of individuals who successfully lost weight; "the basic users" had 37.61% weight loss success; and "the power users" achieved the highest percentage of weight loss success at 72.70%. Behavioral factors delineated the subgroups, though app-related behavioral characteristics further distinguished them. Results were replicated in further analyses with separate subsamples.
Conclusions: This study demonstrates that distinct subgroups can be identified in "messy" commercial app data and the identified subgroups can be replicated in independent samples. Behavioral factors and use of custom app features characterized the subgroups. Targeting and tailoring information to particular subgroups could enhance weight loss success. Future studies should replicate data mining analyses to increase methodology rigor.
C1 [Serrano, Katrina J.; Yu, Mandi] NCI, 9609 Med Ctr Dr, Bethesda, MD 20814 USA.
[Coa, Kisha I.; Atienza, Audie A.] ICF Int, Rockville, MD USA.
[Collins, Linda M.] Penn State Univ, State Coll, PA USA.
RP Serrano, KJ (reprint author), NCI, 9609 Med Ctr Dr, Bethesda, MD 20814 USA.
EM katrina.serrano@nih.gov
RI Emchi, Karma/Q-1952-2016;
OI Serrano, Katrina/0000-0003-4431-3589; Coa, Kisha/0000-0001-5637-259X;
Atienza, Audie/0000-0001-8745-0167
NR 40
TC 0
Z9 0
U1 5
U2 5
PU JMIR PUBLICATIONS, INC
PI TORONTO
PA 59 WINNERS CIRCLE, TORONTO, ON M4L 3Y7, CANADA
SN 1438-8871
J9 J MED INTERNET RES
JI J. Med. Internet Res.
PD JUN
PY 2016
VL 18
IS 6
AR e154
DI 10.2196/jmir.5473
PG 11
WC Health Care Sciences & Services; Medical Informatics
SC Health Care Sciences & Services; Medical Informatics
GA EC9WO
UT WOS:000388495200014
PM 27301853
ER
PT J
AU Flegel, WA
AF Flegel, Willy Albert
TI Red cell alloimmunisation: incidence and prevention
SO LANCET HAEMATOLOGY
LA English
DT Editorial Material
C1 [Flegel, Willy Albert] NIH, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA.
RP Flegel, WA (reprint author), NIH, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA.
EM waf@nih.gov
NR 10
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 2352-3026
J9 LANCET HAEMATOL
JI Lancet Haematol.
PD JUN
PY 2016
VL 3
IS 6
BP E260
EP E261
DI 10.1016/S2352-3026(16)30043-6
PG 2
WC Hematology
SC Hematology
GA ED7SB
UT WOS:000389069100004
PM 27264033
ER
PT J
AU Bok, K
Prevots, DR
Binder, AM
Parra, GI
Strollo, S
Fahle, GA
Behrle-Yardley, A
Johnson, JA
Levenson, EA
Sosnovtsev, SV
Holland, SM
Palmore, TN
Green, KY
AF Bok, Karin
Prevots, D. Rebecca
Binder, Alison M.
Parra, Gabriel I.
Strollo, Sara
Fahle, Gary A.
Behrle-Yardley, Allison
Johnson, Jordan A.
Levenson, Eric A.
Sosnovtsev, Stanislav V.
Holland, Steven M.
Palmore, Tara N.
Green, Kim Y.
TI Epidemiology of Norovirus Infection Among Immunocompromised Patients at
a Tertiary Care Research Hospital, 2010-2013
SO OPEN FORUM INFECTIOUS DISEASES
LA English
DT Article
DE epidemiology; immunocompromised; norovirus
ID NORWALK-LIKE VIRUSES; ORGAN TRANSPLANT RECIPIENTS; HEMATOPOIETIC
STEM-CELL; MONOCLONAL-ANTIBODIES; UNITED-STATES; IN-VIVO;
GASTROENTERITIS; EVOLUTION; TRANSMISSION; POPULATIONS
AB Background. Noroviruses are a major cause of infectious gastroenteritis worldwide, and viruses can establish persistent infection in immunocompromised individuals. Risk factors and transmission in this population are not fully understood.
Methods. From 2010 through 2013, we conducted a retrospective review among immunocompromised patients (n = 268) enrolled in research studies at the National Institutes of Health Clinical Center and identified a subset of norovirus-positive patients (n = 18) who provided stool specimens for norovirus genotyping analysis.
Results. Norovirus genome was identified by reverse-transcription quantitative polymerase chain reaction in stools of 35 (13%) of the 268 immunocompromised patients tested, and infection prevalence was 21% (11 of 53) in persons with primary immune deficiencies and 12% (20 of 166) among persons with solid tumors or hematologic malignancies. Among 18 patients with norovirus genotyping information, norovirus GII. 4 was the most prevalent genotype (14 of 18, 78%). Persistent norovirus infection (>= 6 months) was documented in 8 of 18 (44%) individuals. Phylogenetic analysis of the GII. 4 capsid protein sequences identified at least 5 now-displaced GII. 4 variant lineages, with no evidence of their nosocomial transmission in the Clinical Center.
Conclusions. Norovirus was a leading enteric pathogen identified in this immunocompromised population. Both acute and chronic norovirus infections were observed, and these were likely community-acquired. Continued investigation will further define the role of noroviruses in these patients and inform efforts toward prevention and treatment.
C1 [Bok, Karin; Parra, Gabriel I.; Behrle-Yardley, Allison; Johnson, Jordan A.; Levenson, Eric A.; Sosnovtsev, Stanislav V.; Green, Kim Y.] NIAID, Infect Dis Lab, Bethesda, MD 20892 USA.
[Prevots, D. Rebecca; Binder, Alison M.; Strollo, Sara; Holland, Steven M.; Palmore, Tara N.] NIAID, Lab Clin Infect Dis, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Palmore, Tara N.] NIH, Hosp Epidemiol Serv, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA.
[Fahle, Gary A.] NIH, Microbiol Serv, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA.
[Bok, Karin] US Dept HHS, Natl Vaccine Program Off, Off Assistant Secretary Hlth, Washington, DC USA.
RP Green, KY (reprint author), NIAID, Caliciviruses Sect, Infect Dis Lab, NIH, 50 South Dr,Bldg 50,Room 6318, Bethesda, MD 20892 USA.
EM kgreen@niaid.nih.gov
OI Parra, Gabriel/0000-0002-1102-4740
NR 47
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 2328-8957
J9 OPEN FORUM INFECT DI
JI Open Forum Infect. Dis.
PD SUM
PY 2016
VL 3
IS 3
DI 10.1093/ofid/ofw169
PG 8
WC Infectious Diseases
SC Infectious Diseases
GA ED0YZ
UT WOS:000388571700011
ER
PT J
AU Clancy, CJ
Meslin, C
Badrane, H
Cheng, SJ
Losada, LC
Nierman, WC
Vergidis, P
Clark, NL
Nguyen, MH
AF Clancy, Cornelius J.
Meslin, Camille
Badrane, Hassan
Cheng, Shaoji
Losada, Liliana C.
Nierman, William C.
Vergidis, Pascalis
Clark, Nathan L.
Nguyen, M. Hong
TI Candida albicans Transcriptional Profiling Within Biliary Fluid From a
Patient With Cholangitis, Before and After Antifungal Treatment and
Surgical Drainage
SO OPEN FORUM INFECTIOUS DISEASES
LA English
DT Article
DE Candida albicans; cholangitis; fluconazole; RNA-Seq; transcriptional
profiling
ID DIFFERENTIAL EXPRESSION ANALYSIS; GENE-EXPRESSION; RNA-SEQ; HOST;
INFECTION
AB We used ribonucleic acid sequencing to profile Candida albicans transcription within biliary fluid from a patient with cholangitis; samples were collected before and after treatment with fluconazole and drainage. Candida albicans transcriptomes at the infection site distinguished treated from untreated cholangitis. After treatment, 1131 C. albicans genes were differentially expressed in biliary fluid. Up-regulated genes were enriched in hyphal growth, cell wall organization, adhesion, oxidation reduction, biofilm, and fatty acid and ergosterol biosynthesis. This is the first study to define Candida global gene expression during deep-seated human infection. Successful treatment of cholangitis induced C. albicans genes involved in fluconazole responses and pathogenesis.
C1 [Clancy, Cornelius J.; Badrane, Hassan; Cheng, Shaoji; Vergidis, Pascalis; Nguyen, M. Hong] Univ Pittsburgh, Dept Med, Pittsburgh, PA 15260 USA.
[Clancy, Cornelius J.] Univ Pittsburgh, Sch Med, Div Infect Dis, VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15260 USA.
[Meslin, Camille; Clark, Nathan L.] Univ Pittsburgh, Sch Med, Dept Computat & Syst Biol, Pittsburgh, PA 15260 USA.
[Losada, Liliana C.; Nierman, William C.] J Craig Venter Inst, Rockville, MD USA.
[Losada, Liliana C.] NIAID, 9000 Rockville Pike, Bethesda, MD 20892 USA.
RP Nguyen, MH (reprint author), Univ Pittsburgh, Scaife Hall,Suite 871,3550 Terrace St, Pittsburgh, PA 15261 USA.
EM mhn5@pitt.edu
NR 15
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 2328-8957
J9 OPEN FORUM INFECT DI
JI Open Forum Infect. Dis.
PD SUM
PY 2016
VL 3
IS 3
DI 10.1093/ofid/ofw120
PG 5
WC Infectious Diseases
SC Infectious Diseases
GA ED0YZ
UT WOS:000388571700016
ER
PT J
AU Cha, SA
Yun, JS
Lim, TS
Hwang, S
Yim, EJ
Song, KH
Yoo, KD
Park, YM
Ahn, YB
Ko, SH
AF Cha, Seon-Ah
Yun, Jae-Seung
Lim, Tae-Seok
Hwang, Seawon
Yim, Eun-Jung
Song, Ki-Ho
Yoo, Ki-Dong
Park, Yong-Moon
Ahn, Yu-Bae
Ko, Seung-Hyun
TI Severe Hypoglycemia and Cardiovascular or All-Cause Mortality in
Patients with Type 2 Diabetes
SO DIABETES & METABOLISM JOURNAL
LA English
DT Article
DE Cardiovascular diseases; Diabetes mellitus; type 2; Mortality; Severe
hypoglycemia
ID ASSOCIATION; EVENTS; RISK; DEATH; COMPLICATIONS; MANAGEMENT; INCREASE;
DISEASE
AB Background: We investigated the association between severe hypoglycemia (SH) and the risk of cardiovascular (CV) or all-cause mortality in patients with type 2 diabetes.
Methods: The study included 1,260 patients aged 25 to 75 years with type 2 diabetes from the Vincent Type 2 Diabetes Resgistry (VDR), who consecutively enrolled (n= 1,260) from January 2000 to December 2010 and were followed up until May 2015 with a median follow-up time of 10.4 years. Primary outcomes were death from any cause or CV death. We investigated the association between the CV or all-cause mortality and various covariates using Cox proportional hazards regression analysis.
Results: Among the 906 participants (71.9%) who completed follow-up, 85 patients (9.4%) had at least one episode of SH, and 86 patients (9.5%) died (9.1 per 1,000 patient-years). Patients who had died were older, had a longer duration of diabetes and hypertension, received more insulin, and had more diabetic microvascular complications at baseline, as compared with surviving patients. The experience of SH was significantly associated with an increased risk of all-cause mortality (hazard ratio [HR], 2.64; 95% confidence interval [CI], 1.39 to 5.02; P= 0.003) and CV mortality (HR, 6.34; 95% CI, 2.02 to 19.87; P= 0.002) after adjusting for sex, age, diabetic duration, hypertension, mean glycosylated hemoglobin levels, diabetic nephropathy, lipid profiles, and insulin use.
Conclusion: We found a strong association between SH and increased risk of all-cause and CV mortality in patients with type 2 diabetes.
C1 [Cha, Seon-Ah; Yun, Jae-Seung; Lim, Tae-Seok; Hwang, Seawon; Yim, Eun-Jung; Song, Ki-Ho; Ahn, Yu-Bae; Ko, Seung-Hyun] Catholic Univ Korea, Coll Med, Dept Internal Med, Div Endocrinol & Metab, Seoul, South Korea.
[Yoo, Ki-Dong] Catholic Univ Korea, Coll Med, Dept Internal Med, Div Cardiol, Seoul, South Korea.
[Park, Yong-Moon] NIEHS, Epidemiol Branch, NIH, Res Triangle Pk, NC 27709 USA.
RP Ko, SH (reprint author), Catholic Univ Korea, St Vincents Hosp, Div Endocrinol & Metab, Dept Internal Med,Coll Med, 93 Jungbu Daero, Suwon 16247, South Korea.
EM kosh@catholic.ac.kr
OI Ko, Seung-Hyun/0000-0003-3703-1479
NR 30
TC 3
Z9 3
U1 1
U2 1
PU KOREAN DIABETES ASSOC
PI SEOUL
PA 1010 RENAISSANCE TOWER BLDG, 14 MANRIJAE-RO, MAPO-GUO, SEOUL, 121-706,
SOUTH KOREA
SN 2233-6079
EI 2233-6087
J9 DIABETES METAB J
JI Diabetes Metab. J.
PD JUN
PY 2016
VL 40
IS 3
BP 202
EP 210
DI 10.4093/dmj.2016.40.3.202
PG 9
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA EC4DZ
UT WOS:000388077700005
ER
PT J
AU Mensah, GA
AF Mensah, George A.
TI From Framingham and Bethesda to North Karelia and Back Turning
Prevention and Population Science Discoveries into Heart Health
SO GLOBAL HEART
LA English
DT Editorial Material
ID CARDIOVASCULAR-DISEASE PREVENTION; COMMUNITY INTERVENTION TRIALS;
STANFORD 5-CITY PROJECT; FOLLOW-UP EXPERIENCE; RISK-FACTORS; PROGRAM;
IMPLEMENTATION; FRAMEWORK
C1 [Mensah, George A.] NHLBI, Ctr Translat Res & Implementat Sci, NIH, Bldg 10, Bethesda, MD 20892 USA.
[Mensah, George A.] NHLBI, Div Cardiovasc Sci, NIH, Bldg 10, Bethesda, MD 20892 USA.
RP Mensah, GA (reprint author), NHLBI, Ctr Translat Res & Implementat Sci, NIH, Bldg 10, Bethesda, MD 20892 USA.; Mensah, GA (reprint author), NHLBI, Div Cardiovasc Sci, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM George.Mensah@nih.gov
NR 22
TC 0
Z9 0
U1 1
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 2211-8160
EI 2211-8179
J9 GLOB HEART
JI Glob. Heart
PD JUN
PY 2016
VL 11
IS 2
BP 247
EP 249
DI 10.1016/j.gheart.2016.05.002
PG 3
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA DW3OF
UT WOS:000383550200014
PM 27242095
ER
PT J
AU Thein, MS
Thein, SL
AF Thein, Mya S.
Thein, Swee L.
TI World Sickle Cell Day 2016: A time for appraisal
SO INDIAN JOURNAL OF MEDICAL RESEARCH
LA English
DT Editorial Material
ID RISK-FACTORS; BABY HUG; DISEASE; CHILDREN; ANEMIA; HYDROXYUREA;
HEMOGLOBIN; MANAGEMENT; MORTALITY; SURVIVAL
C1 [Thein, Mya S.; Thein, Swee L.] NHLBI, Sickle Cell Branch, NIH, Bldg 10, Bethesda, MD 20892 USA.
RP Thein, SL (reprint author), NHLBI, Sickle Cell Branch, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM sl.thein@nih.gov
NR 25
TC 0
Z9 0
U1 0
U2 0
PU MEDKNOW PUBLICATIONS & MEDIA PVT LTD
PI MUMBAI
PA B-9, KANARA BUSINESS CENTRE, OFF LINK RD, GHAKTOPAR-E, MUMBAI, 400075,
INDIA
SN 0971-5916
J9 INDIAN J MED RES
JI Indian J. Med. Res.
PD JUN
PY 2016
VL 143
BP 678
EP 681
DI 10.4103/0971-5916.191917
PG 4
WC Immunology; Medicine, General & Internal; Medicine, Research &
Experimental
SC Immunology; General & Internal Medicine; Research & Experimental
Medicine
GA EA4VC
UT WOS:000386612600002
PM 27748290
ER
PT J
AU Zhang, L
Moss, J
AF Zhang, Li
Moss, Joel
TI Genetic studies yield clues to the pathogenesis of Langerhans cell
histiocytosis
SO EUROPEAN RESPIRATORY JOURNAL
LA English
DT Editorial Material
ID ERDHEIM-CHESTER DISEASE; NRAS MUTATIONS; HIGH PREVALENCE;
LYMPHANGIOLEIOMYOMATOSIS; SIROLIMUS; MAP2K1; CANCER; TSC2; RARE; LCH
C1 [Zhang, Li; Moss, Joel] NHLBI, Cardiovasc & Pulm Branch, NIH, Room 6D05,Bldg 10, Bethesda, MD 20892 USA.
RP Moss, J (reprint author), NHLBI, Cardiovasc & Pulm Branch, NIH, Room 6D05,Bldg 10, Bethesda, MD 20892 USA.
EM mossj@nhlbi.nih.gov
NR 34
TC 0
Z9 0
U1 0
U2 0
PU EUROPEAN RESPIRATORY SOC JOURNALS LTD
PI SHEFFIELD
PA 442 GLOSSOP RD, SHEFFIELD S10 2PX, ENGLAND
SN 0903-1936
EI 1399-3003
J9 EUR RESPIR J
JI Eur. Resp. J.
PD JUN
PY 2016
VL 47
IS 6
BP 1629
EP 1631
DI 10.1183/13993003.00568-2016
PG 3
WC Respiratory System
SC Respiratory System
GA DZ6FE
UT WOS:000385956200009
PM 27246079
ER
PT J
AU Llanos, OL
Galiatsatos, P
Guzman-Velez, E
Patil, SP
Smith, PL
Magnuson, T
Schweitzer, M
Steele, K
Polotsky, VY
Schwartz, AR
AF Llanos, Oscar L.
Galiatsatos, Panagis
Guzman-Velez, Edmarie
Patil, Susheel P.
Smith, Philip L.
Magnuson, Thomas
Schweitzer, Michael
Steele, Kimberley
Polotsky, Vsevolod Y.
Schwartz, Alan R.
TI Pharyngeal collapsibility during sleep is elevated in insulin-resistant
females with morbid obesity
SO EUROPEAN RESPIRATORY JOURNAL
LA English
DT Article
ID UPPER AIRWAY COLLAPSIBILITY; HOMEOSTASIS MODEL ASSESSMENT; EXPIRATORY
LUNG-VOLUME; FAT DISTRIBUTION; VENTILATORY CONTROL; GLUCOSE-METABOLISM;
WEIGHT-LOSS; DIABETES-MELLITUS; APNEA SEVERITY; WOMEN
AB Insulin resistance is associated with sleep apnoea, leading us to hypothesise that it is also associated with elevations in pharyngeal collapsibility, even in the absence of sleep apnoea.
90 bariatric patients were characterised for sleep apnoea, pharyngeal collapsibility and insulin resistance. Patients with a respiratory disturbance index (RDI) > 10 events.h(-1), diabetes mellitus, tonsillar hypertrophy and pulmonary disease were excluded. The remaining 14 females underwent collapsibility measurements (passive critical pressure, Pcritp) during non-rapid eye movement sleep. The homeostasis model assessment (HOMA) index, a measure of insulin resistance, was derived from measurements of fasting glucose and insulin levels, and compared to Pcritp.
Groups with high Pcritp compared to low Pcritp did not differ in age, body mass index or RDI. HOMA and insulin were elevated in the high Pcritp group compared to the low Pcritp group (p<0.02). Pcritp correlated with HOMA (Spearman's rho=0.565, 95% CI 0.104-0.862; p=0.035) and insulin (Spearman's rho=0.609 95% CI 0.196-0.835; p=0.021).
Obese insulin-resistant subjects without frank diabetes or sleep apnoea demonstrate preclinical elevations in pharyngeal collapsibility, which may increase their susceptibility to sleep apnoea. Our findings suggest that insulin resistance could play a significant role in sleep apnoea pathogenesis by generating requisite elevations in pharyngeal collapsibility.
C1 [Llanos, Oscar L.] Univ Arkansas, Dept Med, Little Rock, AR 72204 USA.
[Galiatsatos, Panagis] NIH, Crit Care Med, Bldg 10, Bethesda, MD 20892 USA.
[Guzman-Velez, Edmarie] Univ Iowa, Dept Psychol & Brain Sci, Iowa City, IA USA.
[Patil, Susheel P.; Smith, Philip L.; Polotsky, Vsevolod Y.; Schwartz, Alan R.] Johns Hopkins Univ, Div Pulm & Crit Care Med, Dept Med, Baltimore, MD USA.
[Magnuson, Thomas; Schweitzer, Michael; Steele, Kimberley] Johns Hopkins Univ, Dept Surg, Baltimore, MD USA.
RP Schwartz, AR (reprint author), Johns Hopkins Sleep Disorders Ctr, 5501 Hopkins Bayview Circle, Baltimore, MD 21224 USA.
EM aschwar2@jhmi.edu
FU National Institutes of Health [R01 HL50381, HL128970, HL080105]
FX National Institutes of Health: R01 HL50381, HL128970 and HL080105.
Funding information for this article has been deposited with FundRef.
NR 46
TC 1
Z9 1
U1 0
U2 0
PU EUROPEAN RESPIRATORY SOC JOURNALS LTD
PI SHEFFIELD
PA 442 GLOSSOP RD, SHEFFIELD S10 2PX, ENGLAND
SN 0903-1936
EI 1399-3003
J9 EUR RESPIR J
JI Eur. Resp. J.
PD JUN
PY 2016
VL 47
IS 6
BP 1718
EP 1726
DI 10.1183/13993003.00918-2015
PG 9
WC Respiratory System
SC Respiratory System
GA DZ6FE
UT WOS:000385956200019
PM 27103392
ER
PT J
AU Eder, AF
Ryu, JH
Moss, J
AF Eder, Anne F.
Ryu, Jay H.
Moss, Joel
TI Should lymphangioleiomyomatosis patients be permitted to donate blood?
SO EUROPEAN RESPIRATORY JOURNAL
LA English
DT Letter
ID CELLS
C1 [Eder, Anne F.] NIH, Ctr Clin, Dept Transfus Med, Blood Serv Sect, Bldg 10, Bethesda, MD 20892 USA.
[Ryu, Jay H.] Mayo Clin, Coll Med, Div Pulm & Crit Care Med, Rochester, MN USA.
[Moss, Joel] NHLBI, Cardiovasc & Pulm Branch, NIH, Bldg 10, Bethesda, MD 20892 USA.
RP Moss, J (reprint author), NIH, Bldg 10,Room 6D05,MSC 1590, Bethesda, MD 20892 USA.
EM mossj@nhlbi.nih.gov
NR 9
TC 0
Z9 0
U1 2
U2 2
PU EUROPEAN RESPIRATORY SOC JOURNALS LTD
PI SHEFFIELD
PA 442 GLOSSOP RD, SHEFFIELD S10 2PX, ENGLAND
SN 0903-1936
EI 1399-3003
J9 EUR RESPIR J
JI Eur. Resp. J.
PD JUN
PY 2016
VL 47
IS 6
BP 1883
EP 1884
DI 10.1183/13993003.00410-2016
PG 2
WC Respiratory System
SC Respiratory System
GA DZ6FE
UT WOS:000385956200041
PM 27103385
ER
PT J
AU Larson, KB
Cressey, TR
Yogev, R
Wiznia, A
Hazra, R
Jean-Philippe, P
Graham, B
Gonzalez, A
Britto, P
Carey, VJ
Acosta, EP
AF Larson, Kajal B.
Cressey, Tim R.
Yogev, Ram
Wiznia, Andrew
Hazra, Rohan
Jean-Philippe, Patrick
Graham, Bobbie
Gonzalez, Amy
Britto, Paula
Carey, Vincent J.
Acosta, Edward P.
CA Int Maternal Pediat
Adolescent AIDS Clin Trial Protoco
TI Pharmacokinetics of Once-Daily Darunavir/Ritonavir With and Without
Etravirine in Human Immunodeficiency Virus-Infected Children,
Adolescents, and Young Adults
SO JOURNAL OF THE PEDIATRIC INFECTIOUS DISEASES SOCIETY
LA English
DT Article
DE antiretrovirals; darunavir; etravirine; pediatrics; pharmacokinetics;
ritonavir
ID PLASMA; HIV; PHARMACOLOGY; RALTEGRAVIR; MG
AB Background. Limited data are available for once-daily (QD) darunavir (DRV)/ritonavir (r) in the pediatric population. Coadministration of etravirine (ETR) may alter the pharmacokinetics (PK) of DRV. We evaluated the PK interactions between DRV/r (QD) and ETR QD or twice-daily (BID) in children, adolescents, and young adults.
Methods. Human immunodeficiency virus-infected subjects 9 to <24 years old on optimized background therapy including DRV/r 800/100 mg QD alone or combined with ETR 200 mg BID or ETR 400 mg QD were enrolled. Protocol-defined target drug exposure ranges based on adult data were used to assess the adequacy of each regimen. Intensive 24-hour blood sampling was performed, and PK parameters were determined using noncompartmental analysis.
Results. Thirty-one subjects (14 males) completed the study; 16 received DRV/r QD alone (group 1), 6 received DRV/r plus ETR BID (group 2A), and 9 received DRV/r plus ETR QD (group 2B). The geometric mean (90% confidence interval [CI] geometric mean) for DRV area under the curve at 24 hours (AUC(24)) was 57.9 (49.6-67.6), 74.9 (44.4-126.5), and 66.4 (50.8-86.9) mg x h/L for patients in groups 1, 2A, and 2B, respectively. The increased DRV exposure when coadministered with ETR was not statistically significant. The geometric mean (90% CI geometric mean) of ETR AUC(24) was 8.6 (4.4-16.8) and 11.9 (7.5-18.9) mg x h/L for groups 2A and 2B, respectively, with comparable C-24.
Conclusions. The results suggest that DRV/r QD with ETR 400 mg QD or 200 mg BID is appropriate and support further evaluation of the safety and efficacy of the once-daily regimen in older children, adolescents, and young adults.
C1 [Larson, Kajal B.; Acosta, Edward P.] Univ Alabama, Birmingham B15 2TT, W Midlands, England.
[Cressey, Tim R.] Chiang Mai Univ, Fac Associated Med Sci, Program HIV Prevent & Treatment, Dept Med Technol, Chiang Mai, Thailand.
[Yogev, Ram] Northwestern Univ, Feinberg Sch Med, Childrens Mem Hosp, Chicago, IL 60611 USA.
[Wiznia, Andrew] Jacobi Med Ctr, Bronx, NY USA.
[Hazra, Rohan] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Maternal & Pediat Infect Dis Branch, Bethesda, MD USA.
[Jean-Philippe, Patrick] Div Henry M Jackson Fdn Adv Mil Med Inc, HJF DAIDS, Bethesda, MD USA.
[Graham, Bobbie; Gonzalez, Amy] Frontier Sci & Technol, Amherst, NY USA.
[Britto, Paula] Harvard Sch Publ Hlth, Boston, MA USA.
RP Acosta, EP (reprint author), Univ Alabama Birmingham, Div Clin Pharmacol, Sch Med, 1670 Univ Blvd,Volker Hall,Room 258, Birmingham, AL 35294 USA.
EM eacosta@uab.edu
FU NIAID NIH HHS [UM1 AI068616]
NR 20
TC 1
Z9 1
U1 0
U2 0
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 2048-7193
EI 2048-7207
J9 J PEDIATR INFECT DIS
JI J. Pediatr. Infect. Dis. Soc.
PD JUN
PY 2016
VL 5
IS 2
BP 131
EP 137
DI 10.1093/jpids/piu142
PG 7
WC Infectious Diseases
SC Infectious Diseases
GA DZ8QB
UT WOS:000386134800008
PM 27199469
ER
PT J
AU Musci, RJ
Hart, SR
Ballard, ED
Newcomer, A
Van Eck, K
Ialongo, N
Wilcox, H
AF Musci, Rashelle J.
Hart, Shelley R.
Ballard, Elizabeth D.
Newcomer, Alison
Van Eck, Kathryn
Ialongo, Nicholas
Wilcox, Holly
TI Trajectories of Suicidal Ideation from Sixth through Tenth Grades in
Predicting Suicide Attempts in Young Adulthood in an Urban African
American Cohort
SO SUICIDE AND LIFE-THREATENING BEHAVIOR
LA English
DT Article
ID DIAGNOSTIC INTERVIEW SCHEDULE; RISK-FACTORS; PREVENTION PROGRAM;
ADOLESCENT SUICIDE; OUTCOME EVALUATION; BLACK-ADOLESCENTS; BEHAVIOR;
INTERVENTIONS; CHILDREN; LIFE
AB The trajectory of suicidal ideation across early adolescence may inform the timing of suicide prevention program implementation. This study aimed to identify developmental trajectories of suicidal ideation among an urban cohort of community-residing African Americans (AA) longitudinally followed from middle school through early adulthood (ages 11-19 years). Subtypes based on the developmental course of suicidal ideation from late childhood through midadolescence were identified using longitudinal latent class analysis (LLCA) with 581 AA adolescents (52.7% male; 71.1% free or reduced school meals). The developmental trajectories of suicidal ideation were then used to predict suicide attempts in young adulthood. Our LLCA indicated two subtypes (i.e., ideators and nonideators), with 8% of the sample in the ideator class. This trajectory class shows a peak of suicidal ideation in seventh grade and a steady decline in ideation in subsequent grades. Additionally, suicidal ideation trajectories significantly predicted suicide attempt. Results of these analyses suggest the need for suicide prevention approaches prior to high school for AA youth.
C1 [Musci, Rashelle J.] Johns Hopkins Bloomberg Sch Publ Hlth, 624 N Broadway,Rm 841, Baltimore, MD 21205 USA.
[Hart, Shelley R.] Calif State Univ Chico, Dept Child Dev, Chico, CA 95929 USA.
[Ballard, Elizabeth D.] NIMH, Baltimore, MD USA.
[Newcomer, Alison] Catholic Univ Amer, Dept Psychol, Washington, DC 20064 USA.
[Van Eck, Kathryn] Johns Hopkins Sch Med, Dept Pediat, Baltimore, MD USA.
[Ialongo, Nicholas] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Mental Hlth, Baltimore, MD USA.
[Wilcox, Holly] Johns Hopkins Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD USA.
RP Musci, RJ (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, 624 N Broadway,Rm 841, Baltimore, MD 21205 USA.
EM rmusci1@jhu.edu
NR 53
TC 2
Z9 2
U1 10
U2 10
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0363-0234
EI 1943-278X
J9 SUICIDE LIFE-THREAT
JI Suicide Life-Threat. Behav.
PD JUN
PY 2016
VL 46
IS 3
BP 255
EP 265
DI 10.1111/sltb.12191
PG 11
WC Psychiatry; Psychology, Multidisciplinary
SC Psychiatry; Psychology
GA DZ2XK
UT WOS:000385705800001
PM 26395337
ER
PT J
AU Krist, AH
Glasgow, RE
Heurtin-Roberts, S
Sabo, RT
Roby, DH
Gorin, SNS
Balasubramanian, BA
Estabrooks, PA
Ory, MG
Glenn, BA
Phillips, SM
Kessler, R
Johnson, SB
Rohweder, CL
Fernandez, ME
AF Krist, Alex H.
Glasgow, Russell E.
Heurtin-Roberts, Suzanne
Sabo, Roy T.
Roby, Dylan H.
Gorin, Sherri N. Sheinfeld
Balasubramanian, Bijal A.
Estabrooks, Paul A.
Ory, Marcia G.
Glenn, Beth A.
Phillips, Siobhan M.
Kessler, Rodger
Johnson, Sallie Beth
Rohweder, Catherine L.
Fernandez, Maria E.
CA Mohr Study Grp
TI The impact of behavioral and mental health risk assessments on goal
setting in primary care
SO TRANSLATIONAL BEHAVIORAL MEDICINE
LA English
DT Article
DE Health risk assessment; Primary care; Patient reported measures; Health
behaviors; Mental health; Pragmatic trial
ID STRATEGY; IMPLEMENTATION; INTERVENTIONS; PHYSICIANS; DELIVERY; OUTCOMES;
PROJECT; DIETARY; SYSTEMS; DEATH
AB Patient-centered health risk assessments (HRAs) that screen for unhealthy behaviors, prioritize concerns, and provide feedback may improve counseling, goal setting, and health. To evaluate the effectiveness of routinely administering a patient-centered HRA, My Own Health Report, for diet, exercise, smoking, alcohol, drug use, stress, depression, anxiety, and sleep, 18 primary care practices were randomized to ask patients to complete My Own Health Report (MOHR) before an office visit (intervention) or continue usual care (control). Intervention practice patients were more likely than control practice patients to be asked about each of eight risks (range of differences 5.3-15.8 %, p < 0.001), set goals for six risks (range of differences 3.8-16.6 %, p < 0.01), and improve five risks (range of differences 5.4-13.6 %, p < 0.01). Compared to controls, intervention patients felt clinicians cared more for them and showed more interest in their concerns. Patient-centered health risk assessments improve screening and goal setting.
C1 [Krist, Alex H.; Sabo, Roy T.] Virginia Commonwealth Univ, Dept Family Med & Populat Hlth, POB 980101, Richmond, VA 23298 USA.
[Glasgow, Russell E.] Univ Colorado, Sch Med, Dept Family Med, Denver, CO USA.
[Heurtin-Roberts, Suzanne] NCI, Implementat Sci Team, Div Canc Control & Populat Sci, Rockville, MD USA.
[Sabo, Roy T.] Virginia Commonwealth Univ, Dept Biostat, Richmond, VA USA.
[Gorin, Sherri N. Sheinfeld] NCI, Div Canc Control & Populat Sci, Leidos Biomed Res Inc, Rockville, MD USA.
[Balasubramanian, Bijal A.] Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Dept Epidemiol Human Genet & Environm Sci, Dallas, TX USA.
[Estabrooks, Paul A.; Johnson, Sallie Beth] Carilion Clin, Dept Family & Community Med, Roanoke, VA USA.
[Estabrooks, Paul A.; Johnson, Sallie Beth] Virginia Tech, Human Nutr Foods & Exercise, Blacksburg, VA USA.
[Ory, Marcia G.] Texas A&M Hlth Sci Ctr, Sch Publ Hlth, Dept Hlth Promot & Community Hlth Sci, College Stn, TX USA.
[Glenn, Beth A.] Univ Calif Los Angeles, Dept Hlth Policy & Management, Fielding Sch Publ Hlth, Los Angeles, CA USA.
[Phillips, Siobhan M.] Northwestern Univ, Dept Prevent Med, Chicago, IL 60611 USA.
[Kessler, Rodger] Univ Vermont, Dept Family Med, Burlington, VT USA.
[Rohweder, Catherine L.] Univ N Carolina, Gillings Sch Global Publ Hlth, Consortium Implementat Sci, Chapel Hill, NC USA.
[Fernandez, Maria E.] Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Houston, TX 77030 USA.
[Roby, Dylan H.] Univ Maryland, Sch Publ Hlth, College Pk, MD 20742 USA.
RP Krist, AH (reprint author), Virginia Commonwealth Univ, Dept Family Med & Populat Hlth, POB 980101, Richmond, VA 23298 USA.
EM ahkrist@vcu.edu
FU National Cancer Institute; Agency for Healthcare Research and Quality;
Office of Behavioral and Social Sciences Research; National Center for
Advancing Translational Sciences (CTSA) [ULTR00058]
FX Funding for the MOHR project was provided by the National Cancer
Institute, Agency for Healthcare Research and Quality, Office of
Behavioral and Social Sciences Research, and National Center for
Advancing Translational Sciences (CTSA Grant Number ULTR00058). The
opinions expressed in this manuscript are those of the authors and do
not necessarily reflect those of the funders.
NR 37
TC 1
Z9 1
U1 0
U2 0
PU SPRINGER INTERNATIONAL PUBLISHING AG
PI CHAM
PA GEWERBESTRASSE 11, CHAM, CH-6330, SWITZERLAND
SN 1869-6716
EI 1613-9860
J9 TRANSL BEHAV MED
JI Transl. Behav. Med.
PD JUN
PY 2016
VL 6
IS 2
BP 212
EP 219
DI 10.1007/s13142-015-0384-2
PG 8
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA DY6TL
UT WOS:000385261100007
PM 27356991
ER
PT J
AU Bangdiwala, SI
Bhargava, A
O'Connor, DP
Robinson, TN
Michie, S
Murray, DM
Stevens, J
Belle, SH
Templin, TN
Pratt, CA
AF Bangdiwala, Shrikant I.
Bhargava, Alok
O'Connor, Daniel P.
Robinson, Thomas N.
Michie, Susan
Murray, David M.
Stevens, June
Belle, Steven H.
Templin, Thomas N.
Pratt, Charlotte A.
TI Statistical methodologies to pool across multiple intervention studies
SO TRANSLATIONAL BEHAVIORAL MEDICINE
LA English
DT Article
DE Statistical pooling of studies; Random-effects metaanalysis; Study-level
meta-regression; Multilevel meta-regression; Multilevel structural
models
ID WOMENS HEALTH TRIAL; MINORITY POPULATIONS; CHILDHOOD OBESITY;
FEASIBILITY; PREDICTORS; TAXONOMY; EQUATION; TESTS
AB Combining and analyzing data from heterogeneous randomized controlled trials of complex multiple-component intervention studies, or discussing them in a systematic review, is not straightforward. The present article describes certain issues to be considered when combining data across studies, based on discussions in an NIH-sponsored workshop on pooling issues across studies in consortia (see Belle et al. in Psychol Aging, 18(3): 396-405, 2003). Several statistical methodologies are described and their advantages and limitations are explored. Whether weighting the different studies data differently, or via employing random effects, one must recognize that different pooling methodologies may yield different results. Pooling can be used for comprehensive exploratory analyses of data from RCTs and should not be viewed as replacing the standard analysis plan for each study. Pooling may help to identify intervention components that may be more effective especially for subsets of participants with certain behavioral characteristics. Pooling, when supported by statistical tests, can allow exploratory investigation of potential hypotheses and for the design of future interventions.
C1 [Bangdiwala, Shrikant I.] Univ North Carolina Chapel Hill, Dept Biostat, Chapel Hill, NC 27599 USA.
[Bangdiwala, Shrikant I.] Univ South Africa, Inst Social & Hlth Sci, Johannesburg, South Africa.
[Bhargava, Alok] Univ Maryland, Sch Publ Policy, College Pk, MD 20742 USA.
[O'Connor, Daniel P.] Univ Houston, Texas Obes Res Ctr, Dept Hlth & Human Performance, Houston, TX USA.
[Robinson, Thomas N.] Stanford Univ, Ctr Hlth Weight, Stanford, CA 94305 USA.
[Michie, Susan] UCL, Ctr Behav Change, London, England.
[Michie, Susan] UCL, Dept Clin Educ & Hlth Psychol, London, England.
[Murray, David M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Biostat & Bioinformat Branch, NIH, Rockville, MD USA.
[Stevens, June] Univ North Carolina Chapel Hill, Dept Nutr, Chapel Hill, NC USA.
[Belle, Steven H.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA.
[Templin, Thomas N.] Wayne State Univ, Coll Nursing, Off Hlth Res, Detroit, MI 48202 USA.
[Pratt, Charlotte A.] NHLBI, Div Cardiovasc Sci, Bldg 10, Bethesda, MD 20892 USA.
RP Bangdiwala, SI (reprint author), Univ North Carolina Chapel Hill, Dept Biostat, Chapel Hill, NC 27599 USA.; Bangdiwala, SI (reprint author), Univ South Africa, Inst Social & Hlth Sci, Johannesburg, South Africa.
EM kant@unc.edu
FU NIH National Heart, Lung, and Blood Institute; Eunice Kennedy Shriver
National Institute of Child Health and Development; NIH Office of
Behavioral and Social Sciences Research; NIH Office of Disease
Prevention; Centers for Disease Control and Prevention
FX This manuscript is one of three presented in this journal and was
supported the NIH National Heart, Lung, and Blood Institute, the Eunice
Kennedy Shriver National Institute of Child Health and Development, the
NIH Office of Behavioral and Social Sciences Research, the NIH Office of
Disease Prevention, and the Centers for Disease Control and Prevention.
The content is solely the responsibility of the authors and does not
necessarily represent the official views of the National Institutes of
Health.
NR 26
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER INTERNATIONAL PUBLISHING AG
PI CHAM
PA GEWERBESTRASSE 11, CHAM, CH-6330, SWITZERLAND
SN 1869-6716
EI 1613-9860
J9 TRANSL BEHAV MED
JI Transl. Behav. Med.
PD JUN
PY 2016
VL 6
IS 2
BP 228
EP 235
DI 10.1007/s13142-016-0386-8
PG 8
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA DY6TL
UT WOS:000385261100009
PM 27356993
ER
PT J
AU Tate, DF
Lytle, LA
Sherwood, NE
Haire-Joshu, D
Matheson, D
Moore, SM
Loria, CM
Pratt, C
Ward, DS
Belle, SH
Michie, S
AF Tate, Deborah F.
Lytle, Leslie A.
Sherwood, Nancy E.
Haire-Joshu, Debra
Matheson, Donna
Moore, Shirley M.
Loria, Catherine M.
Pratt, Charlotte
Ward, Dianne S.
Belle, Steven H.
Michie, Susan
TI Deconstructing interventions: approaches to studying behavior change
techniques across obesity interventions
SO TRANSLATIONAL BEHAVIORAL MEDICINE
LA English
DT Article
DE Intervention science; Taxonomy; Pooled analysis
ID EVALUATING COMPLEX INTERVENTIONS; WEIGHT-LOSS INTERVENTIONS;
PHYSICAL-ACTIVITY; IMPROVE HEALTH; TAXONOMY; FIDELITY; TRIALS; ADULTS;
LIFE; IMPLEMENTATION
AB Deconstructing interventions into the specific techniques that are used to change behavior represents a new frontier in behavioral intervention research. This paper considers opportunities and challenges in employing the Behavior Change Techniques Taxonomy (BCTTv1) developed by Michie and colleagues, to code the behavior change techniques (BCTs) across multiple interventions addressing obesity and capture dose received at the technique level. Numerous advantages were recognized for using a shared framework for intervention description. Coding interventions at levels of the social ecological framework beyond the individual level, separate coding for behavior change initiation vs. maintenance, fidelity of BCT delivery, accounting for BCTs mode of delivery, and tailoring BCTs, present both challenges and opportunities. Deconstructing interventions and identifying the dose required to positively impact health-related outcomes could enable important gains in intervention science.
C1 [Tate, Deborah F.; Lytle, Leslie A.] Univ North Carolina Chapel Hill, Gillings Sch Global Publ Hlth, Dept Hlth Behav, Chapel Hill, NC 27599 USA.
[Tate, Deborah F.; Ward, Dianne S.] Univ North Carolina Chapel Hill, Gillings Sch Global Publ Hlth, Dept Nutr, Chapel Hill, NC 27599 USA.
[Sherwood, Nancy E.] HealthPartners Inst Educ & Res, Bloomington, MN USA.
[Haire-Joshu, Debra] Washington Univ, Brown Sch, St Louis, MO USA.
[Matheson, Donna] Stanford Univ, Dept Pediat, Stanford, CA 94305 USA.
[Matheson, Donna] Stanford Univ, Stanford Prevent Res Ctr, Stanford, CA 94305 USA.
[Moore, Shirley M.] Case Western Reserve Univ, Frances Payne Bolton Sch Nursing, Cleveland, OH 44106 USA.
[Loria, Catherine M.; Pratt, Charlotte] NHLBI, NIH, Bldg 10, Bethesda, MD 20892 USA.
[Belle, Steven H.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA.
[Michie, Susan] UCL, Dept Clin Educ & Hlth Psychol, Ctr Behav Change, London, England.
RP Tate, DF (reprint author), Univ North Carolina Chapel Hill, Gillings Sch Global Publ Hlth, Dept Hlth Behav, Chapel Hill, NC 27599 USA.; Tate, DF (reprint author), Univ North Carolina Chapel Hill, Gillings Sch Global Publ Hlth, Dept Nutr, Chapel Hill, NC 27599 USA.
EM dtate@unc.edu
FU National Heart, Lung, and Blood Institute; Eunice Kennedy Shriver
National Institute of Child Health and Human Development; National
Institutes of Health (NIH) Office of Behavioral and Social Science
Research; NIH Office of Disease Prevention, National Institute of
Digestive, Diabetes, and Kidney Diseases, National Center for
Complementary and Integrative Health, National Cancer Institute, Office
of Research on Women's Health; Centers for Disease Control and
Prevention (CDC)
FX Funding for this work comes from the National Heart, Lung, and Blood
Institute, the Eunice Kennedy Shriver National Institute of Child Health
and Human Development, the National Institutes of Health (NIH) Office of
Behavioral and Social Science Research, the NIH Office of Disease
Prevention, National Institute of Digestive, Diabetes, and Kidney
Diseases, National Center for Complementary and Integrative Health,
National Cancer Institute, Office of Research on Women's Health, and the
Centers for Disease Control and Prevention (CDC).
NR 53
TC 3
Z9 3
U1 4
U2 4
PU SPRINGER INTERNATIONAL PUBLISHING AG
PI CHAM
PA GEWERBESTRASSE 11, CHAM, CH-6330, SWITZERLAND
SN 1869-6716
EI 1613-9860
J9 TRANSL BEHAV MED
JI Transl. Behav. Med.
PD JUN
PY 2016
VL 6
IS 2
BP 236
EP 243
DI 10.1007/s13142-015-0369-1
PG 8
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA DY6TL
UT WOS:000385261100010
PM 27356994
ER
PT J
AU Belle, SH
Stevens, J
Cella, D
Foltz, JL
Loria, CM
Murray, DM
Czajkowski, SM
Arteaga, SS
Thom, E
Pratt, CA
AF Belle, Steven H.
Stevens, June
Cella, David
Foltz, Jennifer L.
Loria, Catherine M.
Murray, David M.
Czajkowski, Susan M.
Arteaga, S. Sonia
Thom, Elizabeth
Pratt, Charlotte A.
TI Overview of the obesity intervention taxonomy and pooled analysis
working group
SO TRANSLATIONAL BEHAVIORAL MEDICINE
LA English
DT Review
DE Intervention science; Taxonomy; Pooled analysis
ID RESEARCH DEMONSTRATION PROJECT; HEALTH BEHAVIOR-CHANGE; CHILDHOOD
OBESITY; CORD; CONSORTIUM; OPPORTUNITIES; PREVENTION; DESIGN; TRIALS
AB The National Heart, Lung, and Blood Institute and the National Institutes of Health Office of Disease Prevention convened a meeting on August 29-30,2013 entitled "Obesity Intervention Taxonomy and Pooled Analysis." The overarching goals of the meeting were to understand how to decompose interventions targeting behavior change, and in particular, those that focus on obesity and to combine data from groups of related intervention studies to supplement what can be learned from the individual studies. This paper summarizes the workshop recommendations and provides an overview of the two other papers that originated from the workshop and that address decomposition of behavioral change interventions and pooling of data across diverse studies within a consortium.
C1 [Belle, Steven H.] Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA 15260 USA.
[Stevens, June] Univ N Carolina, Chapel Hill, NC USA.
[Cella, David] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA.
[Foltz, Jennifer L.] Ctr Dis Control & Prevent, Atlanta, GA USA.
[Foltz, Jennifer L.] US PHS, Washington, DC USA.
[Loria, Catherine M.; Czajkowski, Susan M.; Arteaga, S. Sonia; Pratt, Charlotte A.] NHLBI, NIH, Bldg 10, Bethesda, MD 20892 USA.
[Murray, David M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Rockville, MD USA.
[Thom, Elizabeth] George Washington Univ, Washington, DC USA.
RP Belle, SH (reprint author), Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA 15260 USA.
EM belle@edc.pitt.edu
FU National Heart, Lung, and Blood Institute; Eunice Kennedy Shriver
National Institute of Child Health and Human Development; NIH Office of
Behavioral and Social Science Research; NIH Office of Disease
Prevention; Centers for Disease Control and Prevention (CDC); National
Institute of Digestive, Diabetes, and Kidney Diseases; National Center
for Complementary and Integrative Health; National Cancer Institute;
Office of Research on Women's Health
FX The three manuscripts described in this journal were supported by the
National Heart, Lung, and Blood Institute, the Eunice Kennedy Shriver
National Institute of Child Health and Human Development, the NIH Office
of Behavioral and Social Science Research, the NIH Office of Disease
Prevention, National Institute of Digestive, Diabetes, and Kidney
Diseases, National Center for Complementary and Integrative Health,
National Cancer Institute, Office of Research on Women's Health, and the
Centers for Disease Control and Prevention (CDC). The findings and
conclusions are those of the authors and do not necessarily represent
the official position of the National Institutes of Health or the
Centers for Disease Control and Prevention.
NR 19
TC 0
Z9 0
U1 3
U2 3
PU SPRINGER INTERNATIONAL PUBLISHING AG
PI CHAM
PA GEWERBESTRASSE 11, CHAM, CH-6330, SWITZERLAND
SN 1869-6716
EI 1613-9860
J9 TRANSL BEHAV MED
JI Transl. Behav. Med.
PD JUN
PY 2016
VL 6
IS 2
BP 244
EP 259
DI 10.1007/s13142-015-0365-5
PG 16
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA DY6TL
UT WOS:000385261100011
PM 27356995
ER
PT J
AU Hekler, EB
Klasnja, P
Riley, WT
Buman, MP
Huberty, J
Rivera, DE
Martin, CA
AF Hekler, Eric B.
Klasnja, Predrag
Riley, William T.
Buman, Matthew P.
Huberty, Jennifer
Rivera, Daniel E.
Martin, Cesar A.
TI Agile science: creating useful products for behavior change in the real
world
SO TRANSLATIONAL BEHAVIORAL MEDICINE
LA English
DT Article
DE Behavior change; Implementation science; Research methods
ID INTERVENTIONS; HEALTH; FEASIBILITY; GUIDANCE; SYSTEMS; DESIGN; PILOT
AB Evidence-based practice is important for behavioral interventions but there is debate on how best to support real-world behavior change. The purpose of this paper is to define products and a preliminary process for efficiently and adaptively creating and curating a knowledge base for behavior change for real-world implementation. We look to evidence-based practice suggestions and draw parallels to software development. We argue to target three products: (1) the smallest, meaningful, self-contained, and repurposable behavior change modules of an intervention; (2) "computational models" that define the interaction between modules, individuals, and context; and (3) "personalization" algorithms, which are decision rules for intervention adaptation. The "agile science" process includes a generation phase whereby contender operational definitions and constructs of the three products are created and assessed for feasibility and an evaluation phase, whereby effect size estimates/casual inferences are created. The process emphasizes early-and-often sharing. If correct, agile science could enable a more robust knowledge base for behavior change.
C1 [Hekler, Eric B.; Buman, Matthew P.; Huberty, Jennifer; Rivera, Daniel E.; Martin, Cesar A.] Arizona State Univ, Sch Nutr & Hlth Promot, 500 N 3rd St, Phoenix, AZ 85003 USA.
[Klasnja, Predrag] Univ Michigan, Ann Arbor, MI 48109 USA.
[Riley, William T.] NIH, Bldg 10, Bethesda, MD 20892 USA.
RP Hekler, EB (reprint author), Arizona State Univ, Sch Nutr & Hlth Promot, 500 N 3rd St, Phoenix, AZ 85003 USA.
EM ehekler@asu.edu
OI Rivera, Daniel/0000-0002-3141-0577
FU Robert Wood Johnson Foundation [71995]; National Science Foundation
[IIS-1449751]; National Heart Lung and Blood Institute [R01HL125440]
FX This work was funded primarily by a grant from the Robert Wood Johnson
Foundation (PI: Hekler, 71995). The example work described was funded by
the National Science Foundation ( PI: Hekler, IIS-1449751) and the
National Heart Lung and Blood Institute (PI: Klasnja, R01HL125440).
NR 61
TC 3
Z9 3
U1 2
U2 2
PU SPRINGER INTERNATIONAL PUBLISHING AG
PI CHAM
PA GEWERBESTRASSE 11, CHAM, CH-6330, SWITZERLAND
SN 1869-6716
EI 1613-9860
J9 TRANSL BEHAV MED
JI Transl. Behav. Med.
PD JUN
PY 2016
VL 6
IS 2
BP 317
EP 328
DI 10.1007/s13142-016-0395-7
PG 12
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA DY6TL
UT WOS:000385261100020
PM 27357001
ER
PT J
AU Campbell-Washburn, AE
Xue, H
Lederman, RJ
Faranesh, AZ
Hansen, MS
AF Campbell-Washburn, Adrienne E.
Xue, Hui
Lederman, Robert J.
Faranesh, Anthony Z.
Hansen, Michael S.
TI Real-Time Distortion Correction of Spiral and Echo Planar Images Using
the Gradient System Impulse Response Function
SO MAGNETIC RESONANCE IN MEDICINE
LA English
DT Article
DE interventional; spiral; EPI; gradient impulse response; gradient
calibration; off-resonance correction
ID OFF-RESONANCE CORRECTION; MAGNETIC-RESONANCE; FIELD MAP; MRI
AB Purpose: MRI-guided interventions demand high frame rate imaging, making fast imaging techniques such as spiral imaging and echo planar imaging (EPI) appealing. In this study, we implemented a real-time distortion correction framework to enable the use of these fast acquisitions for interventional MRI.
Methods: Distortions caused by gradient waveform inaccuracies were corrected using the gradient impulse response function (GIRF), which was measured by standard equipment and saved as a calibration file on the host computer. This file was used at runtime to calculate the predicted k-space trajectories for image reconstruction. Additionally, the off-resonance reconstruction frequency was modified in real time to interactively deblur spiral images.
Results: Real-time distortion correction for arbitrary image orientations was achieved in phantoms and healthy human volunteers. The GIRF-predicted k-space trajectories matched measured k-space trajectories closely for spiral imaging. Spiral and EPI image distortion was visibly improved using the GIRF-predicted trajectories. The GIRF calibration file showed no systematic drift in 4 months and was demonstrated to correct distortions after 30 min of continuous scanning despite gradient heating. Interactive off-resonance reconstruction was used to sharpen anatomical boundaries during continuous imaging.
Conclusions: This real-time distortion correction framework will enable the use of these high frame rate imaging methods for MRI-guided interventions. (C) 2015 Wiley Periodicals, Inc.
C1 [Campbell-Washburn, Adrienne E.; Xue, Hui; Lederman, Robert J.; Faranesh, Anthony Z.; Hansen, Michael S.] NHLBI, Pulm & Cardiovasc Branch, Div Intramural Res, NIH, Bldg 10, Bethesda, MD 20892 USA.
RP Campbell-Washburn, AE (reprint author), NIH, 9000 Rockville Pike,Bldg 10,Room B1D416, Bethesda, MD 20892 USA.
EM adrienne.campbell@nih.gov
OI lederman, robert/0000-0003-1202-6673
FU National Heart, Lung, and Blood Institute, Division of Intramural
Research [Z01-HL006039, Z01-HL005062]
FX Grant sponsor: National Heart, Lung, and Blood Institute, Division of
Intramural Research; Grant numbers: Z01-HL006039, Z01-HL005062.
NR 21
TC 1
Z9 1
U1 4
U2 5
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0740-3194
EI 1522-2594
J9 MAGN RESON MED
JI Magn. Reson. Med.
PD JUN
PY 2016
VL 75
IS 6
BP 2278
EP 2285
DI 10.1002/mrm.25788
PG 8
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA DY3LS
UT WOS:000384994700006
PM 26114951
ER
PT J
AU Talagala, SL
Sarlls, JE
Liu, SY
Inati, SJ
AF Talagala, S. Lalith
Sarlls, Joelle E.
Liu, Siyuan
Inati, Souheil J.
TI Improvement of Temporal Signal-to-Noise Ratio of GRAPPA Accelerated Echo
Planar Imaging Using a FLASH Based Calibration Scan
SO MAGNETIC RESONANCE IN MEDICINE
LA English
DT Article
DE GRAPPA; temporal SNR; EPI; FLASH; calibration scan
ID RECONSTRUCTIONS; ACQUISITION; ARRAYS; MRI
AB Purpose: To demonstrate that the temporal signal-to-noise ratio (SNR) of generalized autocalibrating partially parallel acquisitions (GRAPPA) accelerated echo planar imaging (EPI) can be enhanced and made more spatially uniform by using a fast low angle shot (FLASH) based calibration scan.
Methods: EPI of a phantom and human brains were acquired at 3 Tesla without and with GRAPPA acceleration factor of 2. The GRAPPA accelerated data were reconstructed using calibration scans acquired with EPI and FLASH acquisition schemes. The increase in temporal signal fluctuation due to GRAPPA reconstruction was quantified and compared. Simulated g-factor maps were also created for different calibration scans.
Results: GRAPPA accelerated phantom data exhibited areas with high g values when using the EPI based calibration for reconstruction. The g-factor maps were uniform when using the FLASH calibration scan. g was greater than 1.1 in 74% of pixels in 64 x 64 data reconstructed with the EPI calibration compared with only 15% when using the FLASH calibration scan. Human data also showed abnormally high g regions when using the EPI calibration but not when using the FLASH calibration scan. Use of the FLASH calibration scan increased the whole brain temporal SNR by similar to 12% without affecting the image quality. Experimental observations were confirmed by simulations.
Conclusion: A calibration scan based on a FLASH acquisition scheme can be used to improve the temporal SNR of GRAPPA accelerated EPI time series. Published 2015. This article is a U.S. Government work and is in the public domain in the USA.
C1 [Talagala, S. Lalith; Sarlls, Joelle E.] NINDS, NIH MRI Res Facil, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
[Liu, Siyuan] Natl Inst Deafness & Other Commun Disorders, Language Sect, Voice Speech & Language Branch, NIH, Bethesda, MD USA.
[Inati, Souheil J.] NIMH, Funct MRI Facil, NIH, Bethesda, MD 20892 USA.
RP Talagala, SL (reprint author), NIH, NIH MRI Res Facil, Bldg 10 Room B1D69,10 Ctr Dr, Bethesda, MD 20892 USA.
EM talagala@nih.gov
FU National Institute of Neurological Disorders and Stroke, National
Institute of Mental Health; National Institute on Deafness and Other
Communication Disorders at NIH
FX This research was supported by the intramural research programs of the
National Institute of Neurological Disorders and Stroke, National
Institute of Mental Health and National Institute on Deafness and Other
Communication Disorders at NIH.
NR 17
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0740-3194
EI 1522-2594
J9 MAGN RESON MED
JI Magn. Reson. Med.
PD JUN
PY 2016
VL 75
IS 6
BP 2362
EP 2371
DI 10.1002/mrm.25846
PG 10
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA DY3LS
UT WOS:000384994700015
PM 26192822
ER
PT J
AU Bouhrara, M
Reiter, DA
Celik, H
Fishbein, KW
Kijowski, R
Spencer, RG
AF Bouhrara, Mustapha
Reiter, David A.
Celik, Hasan
Fishbein, Kenneth W.
Kijowski, Richard
Spencer, Richard G.
TI Analysis of mcDESPOT- and CPMG-Derived Parameter Estimates for
Two-Component Nonexchanging Systems
SO MAGNETIC RESONANCE IN MEDICINE
LA English
DT Article
DE mcDESPOT; CPMG; sloppiness; energy surface, accuracy; precision;
quantitative MRI
ID STATE FREE PRECESSION; STOCHASTIC REGION CONTRACTION; MULTICOMPONENT T2
ANALYSIS; WHITE-MATTER DEVELOPMENT; MULTIPLE-SPIN SYSTEMS; MYELIN WATER
FRACTION; ECHO NMR EXPERIMENTS; MAGNETIZATION-TRANSFER; GRADIENT-ECHO;
OFF-RESONANCE
AB Purpose: To compare the reliability and stability of the multicomponent-driven equilibrium single pulse observation of T-1 and T-2 (mcDESPOT) and Carl-Purcell-Meiboom-Gill (CPMG) approaches to parameter estimation.
Methods: The stability and reliability of mcDESPOT and CPMG-derived parameter estimates were compared through examination of energy surfaces, evaluation of model sloppiness, and Monte Carlo simulations. Comparisons were performed on an equal time basis and assuming a two-component system. Parameter estimation bias, reflecting accuracy, and dispersion, reflecting precision, were derived for a range of signal-to-noise ratios (SNRs) and relaxation parameters.
Results: The energy surfaces for parameters incorporated into the mcDESPOT signal model exhibit flatness, a complex structure of local minima, and instability to noise to a much greater extent than the corresponding surfaces for CPMG. Although both mcDESPOT and CPMG performed well at high SNR, the CPMG approach yielded parameter estimates of considerably greater accuracy and precision at lower SNR.
Conclusion: mcDESPOT and CPMG both permit high-quality parameter estimates under SNR that are clinically achievable under many circumstances, depending upon available hardware and resolution and acquisition time constraints. At moderate to high SNR, the mcDESPOT approach incorporating two-step phase increments can yield accurate parameter estimates while providing values for longitudinal relaxation times that are not available through CPMG. However, at low SNR, the CPMG approach is more stable and provides superior parameter estimates. (C) 2015 Wiley Periodicals, Inc.
C1 [Bouhrara, Mustapha; Reiter, David A.; Celik, Hasan; Fishbein, Kenneth W.; Spencer, Richard G.] NIA, Lab Clin Invest, NIH, Baltimore, MD 21224 USA.
[Kijowski, Richard] Univ Wisconsin, Dept Radiol, Madison, WI 53706 USA.
RP Spencer, RG (reprint author), NIA, Intramural Res Program, BRC 04B-116,251 Bayview Blvd, Baltimore, MD 21224 USA.
EM spencer@helix.nih.gov
OI Fishbein, Kenneth/0000-0002-6353-4603
FU National Institute on Aging, National Institutes of Health Intramural
Research Program
FX Grant sponsor: National Institute on Aging, National Institutes of
Health Intramural Research Program.
NR 89
TC 2
Z9 2
U1 2
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0740-3194
EI 1522-2594
J9 MAGN RESON MED
JI Magn. Reson. Med.
PD JUN
PY 2016
VL 75
IS 6
BP 2406
EP 2420
DI 10.1002/mrm.25801
PG 15
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA DY3LS
UT WOS:000384994700020
PM 26140371
ER
PT J
AU Campbell-Washburn, AE
Atkinson, D
Nagy, Z
Chan, RW
Josephs, O
Lythgoe, MF
Ordidge, RJ
Thomas, DL
AF Campbell-Washburn, Adrienne E.
Atkinson, David
Nagy, Zoltan
Chan, Rachel W.
Josephs, Oliver
Lythgoe, Mark F.
Ordidge, Roger J.
Thomas, David L.
TI Using the Robust Principal Component Analysis Algorithm to Remove RF
Spike Artifacts from MR Images
SO MAGNETIC RESONANCE IN MEDICINE
LA English
DT Article
DE spike noise; robust principal component analysis; stripe artifact
ID MATRIX DECOMPOSITION; DYNAMIC MRI; NOISE; REGISTRATION
AB Purpose: Brief bursts of RF noise during MR data acquisition ("k-space spikes") cause disruptive image artifacts, manifesting as stripes overlaid on the image. RF noise is often related to hardware problems, including vibrations during gradient-heavy sequences, such as diffusion-weighted imaging. In this study, we present an application of the Robust Principal Component Analysis (RPCA) algorithm to remove spike noise from k-space.
Methods: Corrupted k-space matrices were decomposed into their low-rank and sparse components using the RPCA algorithm, such that spikes were contained within the sparse component and artifact-free k-space data remained in the low-rank component. Automated center refilling was applied to keep the peaked central cluster of k-space from misclassification in the sparse component.
Results: This algorithm was demonstrated to effectively remove k-space spikes from four data types under conditions generating spikes: (i) mouse heart T-1 mapping, (ii) mouse heart cine imaging, (iii) human kidney diffusion tensor imaging (DTI) data, and (iv) human brain DTI data. Myocardial T-1 values changed by 86.1 +/- 171 ms following despiking, and fractional anisotropy values were recovered following despiking of DTI data.
Conclusion: The RPCA despiking algorithm will be a valuable postprocessing method for retrospectively removing stripe artifacts without affecting the underlying signal of interest. (C) 2015 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
C1 [Campbell-Washburn, Adrienne E.; Lythgoe, Mark F.] UCL, Ctr Adv Biomed Imaging, London, England.
[Campbell-Washburn, Adrienne E.] NHLBI, Div Intramural Res, Cardiovasc & Pulm Branch, NIH, Bldg 10, Bethesda, MD 20892 USA.
[Atkinson, David; Chan, Rachel W.] UCL, Ctr Med Imaging, London, England.
[Nagy, Zoltan; Josephs, Oliver] UCL, UCL Inst Neurol, Wellcome Trust Ctr Neuroimaging, London, England.
[Nagy, Zoltan] Univ Zurich, Dept Econ, Lab Social & Neural Syst Res SNS Lab, Zurich, Switzerland.
[Josephs, Oliver] Birkbeck Coll, Birkbeck UCL Ctr Neuroimaging, London, England.
[Ordidge, Roger J.] Univ Melbourne, Dept Anat & Neurosci, Melbourne, Vic, Australia.
[Thomas, David L.] UCL, UCL Inst Neurol, Dept Brain Repair & Rehabil, London, England.
RP Campbell-Washburn, AE (reprint author), NIH, 9000 Rockville Pike,Bldg 10,Room B1D416, Bethesda, MD 20892 USA.
EM adrienne.campbell@nih.gov
RI Atkinson, David/C-2270-2008;
OI Atkinson, David/0000-0003-1124-6666; Thomas, David/0000-0003-1491-1641;
Ordidge, Roger/0000-0002-1005-3654; Nagy, Zoltan/0000-0001-6611-6362
FU Wellcome Trust [091593/Z/10/Z]; British Heart Foundation; Engineering
and Physical Sciences Research Council [EP/I018700/1]; National
Institute for Health Research University College London Hospitals
Biomedical Research Centre
FX Grant sponsor: the Wellcome Trust; Grant number: 091593/Z/10/Z; Grant
sponsor: British Heart Foundation; Grant sponsor: Engineering and
Physical Sciences Research Council; Grant number: EP/I018700/1; and
support from the National Institute for Health Research University
College London Hospitals Biomedical Research Centre.
NR 18
TC 2
Z9 2
U1 6
U2 6
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0740-3194
EI 1522-2594
J9 MAGN RESON MED
JI Magn. Reson. Med.
PD JUN
PY 2016
VL 75
IS 6
BP 2517
EP 2525
DI 10.1002/mrm.25851
PG 9
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA DY3LS
UT WOS:000384994700031
PM 26193125
ER
PT J
AU Qian, CQ
Duan, Q
Dodd, S
Koretsky, A
Murphy-Boesch, J
AF Qian, Chunqi
Duan, Qi
Dodd, Steve
Koretsky, Alan
Murphy-Boesch, Joe
TI Sensitivity Enhancement of an Inductively Coupled Local Detector Using a
HEMT-Based Current Amplifier
SO MAGNETIC RESONANCE IN MEDICINE
LA English
DT Article
DE HEMT; negative resistance; current amplifier; MRI; inductive coupling
ID PHASED-ARRAY; FIELD; NMR; MRI; DYNAMICS; FEEDBACK
AB Purpose: To improve the signal transmission efficiency and sensitivity of a local detection coil that is weakly inductively coupled to a larger receive coil.
Methods: The resonant detection coil is connected in parallel with the gate of a high electron mobility transistor (HEMT) transistor without impedance matching. When the drain of the transistor is capacitively shunted to ground, current amplification occurs in the resonator by feedback that transforms a capacitive impedance on the transistor's source to a negative resistance on its gate.
Results: High resolution images were obtained from a mouse brain using a small, 11 mm diameter surface coil that was inductively coupled to a commercial, phased array chest coil. Although the power consumption of the amplifier was only 88 mW, 14 dB gain was obtained with excellent noise performance.
Conclusion: An integrated current amplifier based on a HEMT can enhance the sensitivity of inductively coupled local detectors when weakly coupled. This amplifier enables efficient signal transmission between customized user coils and commercial clinical coils, without the need for a specialized signal interface. Published 2015. This article is a U.S. Government work and is in the public domain in the USA.
C1 [Qian, Chunqi; Duan, Qi; Dodd, Steve; Koretsky, Alan; Murphy-Boesch, Joe] NINDS, Lab Funct & Mol Imaging, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
[Qian, Chunqi] Michigan State Univ, Dept Radiol, E Lansing, MI 48824 USA.
RP Qian, CQ (reprint author), NIH, 10 Ctr Dr Room 1D48, Bethesda, MD 20892 USA.
EM qianc2@ninds.nih.gov
RI Duan, Qi/J-7916-2016
OI Duan, Qi/0000-0002-2407-6611
FU Intramural Research Program of the NINDS at NIH [R00EB016753]
FX Grant sponsor: Intramural Research Program of the NINDS at NIH; Grant
number: R00EB016753.
NR 22
TC 0
Z9 0
U1 2
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0740-3194
EI 1522-2594
J9 MAGN RESON MED
JI Magn. Reson. Med.
PD JUN
PY 2016
VL 75
IS 6
BP 2573
EP 2578
DI 10.1002/mrm.25850
PG 6
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA DY3LS
UT WOS:000384994700037
PM 26192998
ER
PT J
AU Dogan, BA
Berker, D
Arduc, A
Tuna, MM
Nasiroglu, NI
Karakilic, E
Basaran, MN
Isik, S
Tutuncu, Y
Unal, M
Guler, S
AF Dogan, Bercem A.
Berker, Dilek
Arduc, Ayse
Tuna, Mazhar M.
Nasiroglu, Narin I.
Karakilic, Ersen
Basaran, Mehtap N.
Isik, Serhat
Tutuncu, Yasemin
Unal, Mustafa
Guler, Serdar
TI Insulin resistance and androgen levels in eugonadic and hypogonadic
women with prolactinoma
SO MINERVA ENDOCRINOLOGICA
LA English
DT Article
DE Prolactinoma; Androgens; Insulin Resistance
ID HYPERPROLACTINEMIC WOMEN; CHORIONIC-GONADOTROPIN; HORMONE;
STEROIDOGENESIS; RECEPTOR; BINDING
AB BACKGROUND: Hyperprolactinemia is the most common endocrinologic disorder in causing menstrual irregularities. Although the correlation between hyperprolactinemia and menstrual dysfunction is widely known, the etiology of menstrual cycle disorders is not profoundly understood in patients with prolactinoma. We aimed to investigate the correlation between prolactin levels and insulin resistance and hyperandrogenism in patients with prolactinoma.
METHODS: Sixty-four patients with microprolactinoma and 33 healthy women were enrolled. Thirty-six of these patients with prolactinoma (group 1) had an estradiol (E2) level under 30 pg/mL, and 28 (group 2) had an E2 level greater than 30 pg/mL. Blood samples were drawn to measure the levels of the following hormones: Follicle stimulating hormone (FSH), luteinizing hormone (LH), E2, prolactin (PRL), total testosterone (TT), androstenedione (AS) and dehydroepiandrostenedione sulphate (DHEAS). Body Mass Index (BMI of >= 30 kg/m(2)) was excluded from the study. Insulin resistance (IR) was calculated by the HOMA-IR.
RESULTS: BMI was higher in patients with prolactinoma than the control group (P=0.02, P=0.025, respectively). IR and glucose intolerance existence were higher in patients with prolactinoma (P=0.007, P=0.097, respectively) than the healthy women, but these differences did not exist between eugonadic and hypogonadic women with prolactinoma (P=0.020, P=0.032, respectively, Bonferroni correction). TT and AS were higher in eugonadic women with prolactinoma than the control group (P=0.004, P=0.003, Bonferroni correction, respectively).
CONCLUSIONS: Our study revealed that the relationship between hyperprolactinemia and IR/glucose intolerance is irrespective of gonadal status in women with prolactinoma. Also, the study concluded that hyperandrogenism may be a cause of menstrual dysfunction in eugonadic women with prolactinoma.
C1 [Dogan, Bercem A.; Berker, Dilek; Arduc, Ayse; Nasiroglu, Narin I.; Karakilic, Ersen; Basaran, Mehtap N.; Isik, Serhat; Tutuncu, Yasemin; Unal, Mustafa; Guler, Serdar] Ankara Numune Training & Res Hosp, Endocrinol & Metab Dis, Ankara, Turkey.
[Arduc, Ayse] NIDDK, Diabet Endocrine & Obes Branch, NIH, Bethesda, MD 20892 USA.
[Tuna, Mazhar M.] Dicle Univ, Endocrinol & Metab Dis Dept, Diyarbakir, Turkey.
[Guler, Serdar] Hitit Univ, Endocrinol & Metab Dis Dept, Corum, Turkey.
RP Dogan, BA (reprint author), Ankara Numune Training & Res Hosp, Dept Endocrinol & Metab, Ankara, Turkey.
EM bercemay@gmail.com
NR 22
TC 0
Z9 0
U1 0
U2 0
PU EDIZIONI MINERVA MEDICA
PI TURIN
PA CORSO BRAMANTE 83-85 INT JOURNALS DEPT., 10126 TURIN, ITALY
SN 0391-1977
EI 1827-1634
J9 MINERVA ENDOCRINOL
JI Minerva Endocrinol.
PD JUN
PY 2016
VL 41
IS 2
BP 175
EP 182
PG 8
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA DY2TM
UT WOS:000384945000004
PM 25288097
ER
PT J
AU Deshpande, N
Simonsick, E
Metter, EJ
Ko, S
Ferrucci, L
Studenski, S
AF Deshpande, Nandini
Simonsick, Eleanor
Metter, E. Jeffrey
Ko, Seunguk
Ferrucci, Luigi
Studenski, Stephanie
TI Ankle proprioceptive acuity is associated with objective as well as
self-report measures of balance, mobility, and physical function
SO AGE
LA English
DT Article
DE Ankle proprioception; Threshold for perception of passive movement;
Balance; Gait speed; Mobility; Aging
ID OLDER-ADULTS; PERFORMANCE; POPULATION; MUSCLE; YOUNG; SWAY; AGE
AB Ankle proprioceptive information is integrated by the central nervous system to generate and modulate muscle contractions for maintaining standing balance. This study evaluated the association of ankle joint proprioception with objective and self-report measures of balance, mobility, and physical function across the adult life span. Seven hundred and ninety participants (age range 24-97 years, 362 women) who completed ankle proprioception assessment between 2010 and 2014 were included in the present study from the population-based cohort of the Baltimore Longitudinal Study of Aging (BLSA), USA. Outcome measures included ankle joint proprioception measured as threshold for perception of passive movement (TPPM); single leg stance time; perceived difficulty for standing balance; usual, fastest, and narrow-path gait speed; walking index; short physical performance battery score; and self-reported activity restriction due to fear of falling. Descriptive variables included age, sex, body mass index, education, strength, and cognition. Analyses of covariance (ANCOVA) in general linear model (GLM) or multinomial logistic regression analyses were performed, as appropriate, to test the hypothesis that balance, mobility, and physical function were significantly different according to TPPM quintiles even after adjusting for relevant covariates. Those with TPPM >2.2 degrees consistently demonstrated poor balance, mobility, and physical function. However, with increase in challenge (single leg stance, fastest walking speed, and SPPB), TPPM >1.4 degrees was associated with significantly worse performance. In conclusion, ankle proprioceptive acuity has an overall graded relationship with objective and self-report measures of balance, mobility, and physical function. However, the cutoff proprioceptive acuity associated with substantial decline or inability to perform could depend on the challenge induced.
C1 [Deshpande, Nandini] Queens Univ, Fac Hlth Sci, Louise D Acton Bldg,31 George St, Kingston, ON K7L 3N6, Canada.
[Simonsick, Eleanor; Ferrucci, Luigi; Studenski, Stephanie] NIA, Clin Res Branch, Baltimore, MD 21224 USA.
[Metter, E. Jeffrey] Univ Tennessee, Med Ctr, Dept Neurol, Memphis, TN USA.
[Ko, Seunguk] Chonnam Natl Univ, Dept Mech Engn, Gwangju, Jeonnam, South Korea.
RP Deshpande, N (reprint author), Queens Univ, Fac Hlth Sci, Louise D Acton Bldg,31 George St, Kingston, ON K7L 3N6, Canada.
EM nandinijd@yahoo.com
FU National Institute on Aging's Intramural Research Funds
FX The Baltimore Longitudinal Study of Aging was conducted as a component
of the Intramural Research Program of the National Institute on Aging.
This study was funded by National Institute on Aging's Intramural
Research Funds.
NR 29
TC 1
Z9 1
U1 1
U2 2
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0161-9152
EI 1574-4647
J9 AGE
JI Age
PD JUN
PY 2016
VL 38
IS 3
AR 53
DI 10.1007/s11357-016-9918-x
PG 9
WC Geriatrics & Gerontology
SC Geriatrics & Gerontology
GA DX9RZ
UT WOS:000384734100006
PM 27146830
ER
PT J
AU Sterling, NW
Lichtenstein, M
Lee, EY
Lewis, MM
Evans, A
Eslinger, PJ
Du, GW
Gao, X
Chen, HL
Kong, L
Huang, XM
AF Sterling, Nicholas W.
Lichtenstein, Maya
Lee, Eun-Young
Lewis, Mechelle M.
Evans, Alicia
Eslinger, Paul J.
Du, Guangwei
Gao, Xiang
Chen, Honglei
Kong, Lan
Huang, Xuemei
TI Higher Plasma LDL-Cholesterol is Associated with Preserved Executive and
Fine Motor Functions in Parkinson's Disease
SO AGING AND DISEASE
LA English
DT Article
DE Parkinson's disease; cholesterol; low density lipoprotein cholesterol
(LDL-cholesterol); cognition; neuroprotection; executive function
ID MILD COGNITIVE IMPAIRMENT; GLIA-DERIVED CHOLESTEROL; SERUM-CHOLESTEROL;
RISK-FACTORS; REDUCED RISK; DEMENTIA; SYNAPTOGENESIS; MULTICENTER;
DENERVATION; ASSESSMENTS
AB Plasma low density lipoprotein (LDL) cholesterol has been associated both with risk of Parkinson's disease (PD) and with age-related changes in cognitive function. This prospective study examined the relationship between baseline plasma LDL-cholesterol and cognitive changes in PD and matched Controls. Fasting plasma LDL-cholesterol levels were obtained at baseline from 64 non-demented PD subjects (62.7 +/- 7.9 y) and 64 Controls (61.3 +/- 6.8 y). Subjects underwent comprehensive neuropsychological testing at baseline, 18-, and 36-months. Linear mixed-effects modeling was used to assess the relationships between baseline LDL-cholesterol levels and longitudinal cognitive changes. At baseline, PD patients had lower scores of fine motor (p< 0.0001), executive set shifting (p= 0.018), and mental processing speed (p= 0.049) compared to Controls. Longitudinally, Controls demonstrated improved fine motor and memory test scores (p= 0.044, and p= 0.003), whereas PD patients demonstrated significantly accelerated loss in fine motor skill (p= 0.002) compared to Controls. Within the PD group, however, higher LDL-cholesterol levels were associated with improved executive set shifting (beta= 0.003, p< 0.001) and fine motor scores (beta= 0.002, p= 0.030) over time. These associations were absent in Controls (p> 0.7). The cholesterol - executive set shifting association differed significantly between PDs and Controls (interaction p= 0.005), whereas the cholesterol fine motor association difference did not reach significance (interaction, p= 0.104). In summary, higher plasma LDL-cholesterol levels were associated with better executive function and fine motor performance over time in PD, both of which may reflect an effect on nigrostriatal mediation. Confirmation of these results and elucidation of involved mechanisms are warranted, and might lead to feasible therapeutic strategies.
C1 [Sterling, Nicholas W.; Lichtenstein, Maya; Lee, Eun-Young; Lewis, Mechelle M.; Evans, Alicia; Eslinger, Paul J.; Du, Guangwei; Huang, Xuemei] Penn State Univ, Milton S Hershey Med Ctr, Dept Neurol, Hershey, PA 17033 USA.
[Eslinger, Paul J.; Kong, Lan] Penn State Univ, Milton S Hershey Med Ctr, Dept Pharmacol, Hershey, PA 17033 USA.
[Lewis, Mechelle M.; Huang, Xuemei] Penn State Univ, Milton S Hershey Med Ctr, Dept Publ Hlth Sci, Hershey, PA 17033 USA.
[Eslinger, Paul J.; Huang, Xuemei] Penn State Univ, Milton S Hershey Med Ctr, Dept Radiol, Hershey, PA 17033 USA.
[Huang, Xuemei] Penn State Univ, Milton S Hershey Med Ctr, Dept Neurosurg, Hershey, PA 17033 USA.
[Huang, Xuemei] Penn State Univ, Milton S Hershey Med Ctr, Dept Kinesiol, Hershey, PA 17033 USA.
[Gao, Xiang] Penn State Univ, Dept Nutr Sci, University Pk, PA 16802 USA.
[Chen, Honglei] NIEHS, Epidemiol Branch, Aging & Neuroepidemiol Grp, Res Triangle Pk, NC 27709 USA.
RP Huang, XM (reprint author), Penn State Univ, Milton S Hershey Med Ctr, Dept Neurol, Hershey, PA 17033 USA.; Huang, XM (reprint author), Penn State Univ, Milton S Hershey Med Ctr, Dept Pharmacol, Hershey, PA 17033 USA.; Huang, XM (reprint author), Penn State Univ, Milton S Hershey Med Ctr, Dept Kinesiol, Hershey, PA 17033 USA.
EM xuemei@psu.edu
OI Chen, Honglei/0000-0003-3446-7779
FU National Institute Neurological Disorders and Stroke [NS060722,
NS082151]; Hershey Medical Center GCRC (National Institute of Health)
[M01RR10732]; GCRC Construction Grant [C06RR016499]; Pennsylvania
Department of Health Tobacco CURE Funds; intramural research program of
the National Institute of Environmental Health Sciences [Z01-ES-101986]
FX This work was supported by the National Institute Neurological Disorders
and Stroke (NS060722 and NS082151 to XH), the Hershey Medical Center
GCRC (National Institute of Health M01RR10732), the GCRC Construction
Grant (C06RR016499), the Pennsylvania Department of Health Tobacco CURE
Funds, and the intramural research program of the National Institute of
Environmental Health Sciences (Z01-ES-101986). All analyses,
interpretations, and conclusions are those of the authors and not the
research sponsors.
NR 50
TC 0
Z9 0
U1 2
U2 3
PU INT SOC AGING & DISEASE
PI FORT WORTH
PA EDITORIAL OFF, 3400 CAMP BOWIE BLVD, FORT WORTH, TX 76106 USA
SN 2152-5250
J9 AGING DIS
JI Aging Dis.
PD JUN
PY 2016
VL 7
IS 3
BP 237
EP 245
DI 10.14336/AD.2015.1030
PG 9
WC Geriatrics & Gerontology
SC Geriatrics & Gerontology
GA DY1FJ
UT WOS:000384840000005
PM 27330838
ER
PT J
AU Freedman, DM
Wu, JC
Chen, HL
Engels, EA
Enewold, LR
Freedman, ND
Goedert, JJ
Kuncl, RW
Gail, MH
Pfeiffer, RM
AF Freedman, D. Michal
Wu, Jincao
Chen, Honglei
Engels, Eric A.
Enewold, Lindsey R.
Freedman, Neal D.
Goedert, James J.
Kuncl, Ralph W.
Gail, Mitchell H.
Pfeiffer, Ruth M.
TI Associations between cancer and Parkinson's disease in US elderly adults
SO INTERNATIONAL JOURNAL OF EPIDEMIOLOGY
LA English
DT Article
DE Cancer; Parkinson's disease; Medicare; SEER Program
ID REPRODUCTIVE FACTORS; PROSPECTIVE COHORT; MALIGNANT-MELANOMA; MEDICARE
DATA; EPIDEMIOLOGY; RISK; DIAGNOSIS; SMOKING; AGE; SURVEILLANCE
AB Background: Several studies suggest that cancer is reduced before and after a Parkinson's disease (PD) diagnosis. However, determining relationships among diseases of ageing is challenging due to possible biases in ascertaining disease. This study evaluates the PD and cancer relationship, addressing potential biases.
Methods: Using Surveillance, Epidemiology, and End Results-Medicare linked data (1992-2005) of adults >= 65 years, we assessed PD risk after cancer comparing PD in 743 779 cancer patients with PD in a non-cancer group (n = 419 432) in prospective cohort analyses. We also conducted a case-control study of 836 947 cancer cases and 142 869 controls to assess cancer following PD. We applied Cox proportional hazards models to estimate hazards ratios (HRs) for PD after cancer and unconditional logistic regression to estimate odds ratios (ORs) for PD preceding cancer, controlling for physician visits and other factors. To explore biases in ascertaining cancer, we examined relationships between cancer and automobile accident injuries, which we expected to be null.
Results: No association was observed between cancer and subsequent PD [ HR = 0.97; 95% confidence interval (CI) = 0.92-1.01] nor between cancer and subsequent automobile injuries (HR = 1.03; 95% CI = 0.98-1.07). One site, lung cancer, was associated with subsequent reduced PD, which may reflect confounding by smoking. In the case-control analysis, PD was associated with reduced subsequent cancer, overall (OR = 0.77; 95% CI = 0.71-0.82) and for several cancer sites. However, the automobile injury/subsequent cancer association was similar (OR = 0.83; 95% CI = 0.78-0.88), suggesting a cancer detection bias after serious health outcomes.
Conclusions: In totality, our data do not support a biological relationship between PD and cancer.
C1 [Freedman, D. Michal; Wu, Jincao; Engels, Eric A.; Freedman, Neal D.; Goedert, James J.; Gail, Mitchell H.; Pfeiffer, Ruth M.] NCI, Div Canc Epidemiol & Genet, 9609 Med Ctr Dr,7E538, Rockville, MD 20850 USA.
[Wu, Jincao] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA.
[Chen, Honglei] NIEHS, Aging & Neuroepidemiol Grp, POB 12233, Res Triangle Pk, NC 27709 USA.
[Enewold, Lindsey R.] NCI, Div Canc Control & Populat Sci, 9609 Med Ctr Dr,7E538, Rockville, MD 20850 USA.
[Kuncl, Ralph W.] Univ Redlands, Dept Biol, Redlands, CA 92373 USA.
RP Freedman, DM (reprint author), NCI, Div Canc Epidemiol & Genet, 9609 Med Ctr Dr,7E538, Rockville, MD 20850 USA.
EM freedmam@mail.nih.gov
OI Chen, Honglei/0000-0003-3446-7779
FU Intramural Research Program of the National Cancer Institute; National
Institute of Environmental Health Sciences, National Institutes of
Health; US Public Health Service
FX This work was supported by the Intramural Research Program of the
National Cancer Institute and the National Institute of Environmental
Health Sciences, National Institutes of Health and the US Public Health
Service.
NR 37
TC 2
Z9 2
U1 4
U2 4
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0300-5771
EI 1464-3685
J9 INT J EPIDEMIOL
JI Int. J. Epidemiol.
PD JUN
PY 2016
VL 45
IS 3
BP 741
EP 751
DI 10.1093/ije/dyw016
PG 11
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA DX8QG
UT WOS:000384653200028
PM 26989123
ER
PT J
AU Anantharaman, D
Muller, DC
Lagiou, P
Ahrens, W
Holcatova, I
Merletti, F
Kjaerheim, K
Polesel, J
Simonato, L
Canova, C
Castellsague, X
Macfarlane, TV
Znaor, A
Thomson, P
Robinson, M
Conway, DI
Healy, CM
Tjonneland, A
Westin, U
Ekstrom, J
Chang-Claude, J
Kaaks, R
Overvad, K
Drogan, D
Hallmans, G
Laurell, G
Bueno-de-Mesquita, HB
Peeters, PH
Agudo, A
Larranaga, N
Travis, RC
Palli, D
Barricarte, A
Trichopoulou, A
George, S
Trichopoulos, D
Quiros, JR
Grioni, S
Sacerdote, C
Navarro, C
Sanchez, MJ
Tumino, R
Severi, G
Boutron-Ruault, MC
Clavel-Chapelon, F
Panico, S
Weiderpass, E
Lund, E
Gram, IT
Riboli, E
Pawlita, M
Waterboer, T
Kreimer, AR
Johansson, M
Brennan, P
AF Anantharaman, Devasena
Muller, David C.
Lagiou, Pagona
Ahrens, Wolfgang
Holcatova, Ivana
Merletti, Franco
Kjaerheim, Kristina
Polesel, Jerry
Simonato, Lorenzo
Canova, Cristina
Castellsague, Xavier
Macfarlane, Tatiana V.
Znaor, Ariana
Thomson, Peter
Robinson, Max
Conway, David I.
Healy, Claire M.
Tjonneland, Anne
Westin, Ulla
Ekstrom, Johanna
Chang-Claude, Jenny
Kaaks, Rudolf
Overvad, Kim
Drogan, Dagmar
Hallmans, Goran
Laurell, Goran
Bueno-de-Mesquita, H. B.
Peeters, Petra H.
Agudo, Antonio
Larranaga, Nerea
Travis, Ruth C.
Palli, Domenico
Barricarte, Aurelio
Trichopoulou, Antonia
George, Saitakis
Trichopoulos, Dimitrios
Ramon Quiros, J.
Grioni, Sara
Sacerdote, Carlotta
Navarro, Carmen
Sanchez, Maria-Jose
Tumino, Rosario
Severi, Gianluca
Boutron-Ruault, Marie-Christine
Clavel-Chapelon, Francoise
Panico, Salvatore
Weiderpass, Elisabete
Lund, Eiliv
Gram, Inger T.
Riboli, Elio
Pawlita, Michael
Waterboer, Tim
Kreimer, Aimee R.
Johansson, Mattias
Brennan, Paul
TI Combined effects of smoking and HPV16 in oropharyngeal cancer
SO INTERNATIONAL JOURNAL OF EPIDEMIOLOGY
LA English
DT Article
DE Human papillomavirus; tobacco smoking; interaction; head and neck cancer
risk; oropharynx cancer
ID HUMAN-PAPILLOMAVIRUS SEROLOGY; NECK-CANCER; INTERNATIONAL AGENCY;
DATA-COLLECTION; POOLED ANALYSIS; HEAD; ALCOHOL; TOBACCO; RISK;
ASSOCIATION
AB Background: Although smoking and HPV infection are recognized as important risk factors for oropharyngeal cancer, how their joint exposure impacts on oropharyngeal cancer risk is unclear. Specifically, whether smoking confers any additional risk to HPV-positive oropharyngeal cancer is not understood.
Methods: Using HPV serology as a marker of HPV-related cancer, we examined the interaction between smoking and HPV16 in 459 oropharyngeal (and 1445 oral cavity and laryngeal) cancer patients and 3024 control participants from two large European multicentre studies. Odds ratios and credible intervals [CrI], adjusted for potential confounders, were estimated using Bayesian logistic regression.
Results: Both smoking [odds ratio (OR [CrI]: 6.82 [4.52, 10.29]) and HPV seropositivity (OR [CrI]: 235.69 [99.95, 555.74]) were independently associated with oropharyngeal cancer. The joint association of smoking and HPV seropositivity was consistent with that expected on the additive scale (synergy index [CrI]: 1.32 [0.51, 3.45]), suggesting they act as independent risk factors for oropharyngeal cancer.
Conclusions: Smoking was consistently associated with increase in oropharyngeal cancer risk in models stratified by HPV16 seropositivity. In addition, we report that the prevalence of oropharyngeal cancer increases with smoking for both HPV16-positive and HPV16-negative persons. The impact of smoking on HPV16-positive oropharyngeal cancer highlights the continued need for smoking cessation programmes for primary prevention of head and neck cancer.
C1 [Anantharaman, Devasena; Muller, David C.; Johansson, Mattias; Brennan, Paul] Int Agcy Res Canc, Genet Epidemiol Grp, Lyon, France.
[Lagiou, Pagona; George, Saitakis] Univ Athens, Sch Med, Dept Hyg Epidemiol & Med Stat, Athens, Greece.
[Ahrens, Wolfgang] BIPS, Leibniz Inst Prevent Res & Epidemiol, Bremen, Germany.
[Ahrens, Wolfgang] Univ Bremen, Fac Math & Comp Sci, Bremen, Germany.
[Holcatova, Ivana] Charles Univ Prague, Fac Med 1, Inst Hyg & Epidemiol, Prague, Czech Republic.
[Merletti, Franco] Univ Turin, Dept Med Sci, Canc Epidemiol Unit, Turin, Italy.
[Kjaerheim, Kristina] Canc Registry Norway, Oslo, Norway.
[Polesel, Jerry] CRO Aviano Natl Canc Inst, Unit Epidemiol & Biostat, Aviano, Italy.
[Simonato, Lorenzo; Canova, Cristina] Univ Padua, Dept Mol Med, Lab Publ Hlth & Populat Studies, Padua, Italy.
[Castellsague, Xavier] CIBERESP, IDIBELL, ICO, Unit Infect & Canc, Barcelona, Spain.
[Macfarlane, Tatiana V.] Univ Aberdeen, Sch Med & Dent, Aberdeen, Scotland.
[Znaor, Ariana] Croatian Natl Inst Publ Hlth, Croatian Natl Canc Registry, Zagreb, Croatia.
[Znaor, Ariana] Int Agcy Res Canc, Sect Canc Surveillance, Lyon, France.
[Thomson, Peter; Robinson, Max] Newcastle Univ, Ctr Oral Hlth Res, Newcastle Upon Tyne, Tyne & Wear, England.
[Conway, David I.] Univ Glasgow, Sch Dent, Coll Med Vet & Life Sci, Glasgow, Lanark, Scotland.
[Healy, Claire M.] Trinity Coll Dublin, Sch Dent Sci, Dublin, Ireland.
[Tjonneland, Anne] Danish Canc Soc, Inst Canc Epidemiol, Copenhagen, Denmark.
[Westin, Ulla] Lund Univ, Dept Otorhinolaryngol Malmo & Lund, Lund, Sweden.
[Ekstrom, Johanna] Lund Univ, Dept Clin Sci, Lund, Sweden.
[Chang-Claude, Jenny; Kaaks, Rudolf] German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany.
[Overvad, Kim] Inst Publ Hlth, Aarhus, Denmark.
[Drogan, Dagmar] German Inst Human Nutr Potsdam Rehbruecke DIfE, Nuthetal, Germany.
[Hallmans, Goran] Umea Univ, Dept Biobank Res, Umea, Sweden.
[Laurell, Goran] Uppsala Univ, Dept Surg Sci, Uppsala, Sweden.
[Bueno-de-Mesquita, H. B.] Natl Inst Publ Hlth & Environm RIVM, Dept Determinants Chron Dis DCD, Bilthoven, Netherlands.
[Bueno-de-Mesquita, H. B.] Univ Med Ctr, Dept Gastroenterol & Hepatol, Utrecht, Netherlands.
[Bueno-de-Mesquita, H. B.] Imperial Coll London, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England.
[Bueno-de-Mesquita, H. B.] Univ Malaya, Fac Med, Dept Social & Prevent Med, Kuala Lumpur, Malaysia.
[Peeters, Petra H.] Univ Med Ctr, Julius Ctr Hlth Sci & Primary Care, Dept Epidemiol, Utrecht, Netherlands.
[Peeters, Petra H.] Imperial Coll London, Sch Publ Hlth, MRC PHE, London, England.
[Agudo, Antonio] ICO, Unit Nutr & Canc, Barcelona, Spain.
[Larranaga, Nerea] BIODonostia Res Inst, Basque Hlth Dept, Publ Hlth Div Gipuzkoa, San Sebastian, Spain.
[Larranaga, Nerea; Barricarte, Aurelio; Navarro, Carmen; Sanchez, Maria-Jose] CIBER Epidemiol & Publ Hlth CIBERESP, Madrid, Spain.
[Travis, Ruth C.] Univ Oxford, Nuffield Dept Populat Hlth, Canc Epidemiol Unit, Oxford, England.
[Palli, Domenico] Canc Res & Prevent Inst ISPO, Mol & Nutr Epidemiol Unit, Florence, Italy.
[Barricarte, Aurelio] Navarre Publ Hlth Inst, Pamplona, Spain.
[Trichopoulou, Antonia; George, Saitakis; Trichopoulos, Dimitrios] Hellen Hlth Fdn, Athens, Greece.
[Trichopoulou, Antonia; Trichopoulos, Dimitrios] Acad Athens, Bur Epidemiol Res, Athens, Greece.
[Trichopoulos, Dimitrios] Harvard Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.
[Ramon Quiros, J.] Publ Hlth Directorate Asturias, Oviedo, Spain.
[Grioni, Sara] Fdn IRCCS, Ist Nazl Tumori, Epidemiol & Prevent Unit, Milan, Italy.
[Sacerdote, Carlotta] Univ Turin, Citta Salute & Sci Hosp, Canc Epidemiol Unit, Turin, Italy.
[Sacerdote, Carlotta] Ctr Canc Prevent CPO, Turin, Italy.
[Navarro, Carmen] IMIB Arrixaca, Murcia Reg Hlth Council, Dept Epidemiol, Murcia, Spain.
[Navarro, Carmen] Univ Murcia, Dept Hlth & Social Sci, Murcia, Spain.
[Sanchez, Maria-Jose] Univ Granada, Inst Invest Biosanitaria, Granada, Spain.
[Tumino, Rosario] Civ MP Arezzo Hosp, Canc Registry, Asp Ragusa, Ragusa, Italy.
[Tumino, Rosario] Civ MP Arezzo Hosp, Histopathol Unit, Asp Ragusa, Ragusa, Italy.
[Severi, Gianluca] Human Genet Fdn HuGeF, Turin, Italy.
[Severi, Gianluca] Canc Council Victoria, Canc Epidemiol Ctr, Melbourne, Vic, Australia.
[Severi, Gianluca] Univ Melbourne, Melbourne Sch Populat & Global Hlth, Ctr Epidemiol & Biostat, Melbourne, Vic 3010, Australia.
[Boutron-Ruault, Marie-Christine; Clavel-Chapelon, Francoise] INSERM, Ctr Res Epidemiol & Populat Hlth CESP, Villejuif, France.
[Boutron-Ruault, Marie-Christine; Clavel-Chapelon, Francoise] Univ Paris 11, Villejuif, France.
[Boutron-Ruault, Marie-Christine; Clavel-Chapelon, Francoise] Inst Gustave Roussy, Villejuif, France.
[Panico, Salvatore] Univ Naples Federico II, Dipartimento Med Clin & Chirurgia, Naples, Italy.
[Weiderpass, Elisabete; Lund, Eiliv; Gram, Inger T.] Arctic Univ Norway, Univ Tromso, Fac Hlth Sci, Dept Community Med, Tromso, Norway.
[Weiderpass, Elisabete] Canc Registry Norway, Oslo, Norway.
[Weiderpass, Elisabete] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
[Weiderpass, Elisabete] Folkhalsan Res Ctr, Dept Genet Epidemiol, Helsinki, Finland.
[Riboli, Elio] Imperial Coll London, Sch Publ Hlth, London, England.
[Pawlita, Michael; Waterboer, Tim] German Canc Res Ctr, Heidelberg, Germany.
[Kreimer, Aimee R.] NCI, NIH, Bethesda, MD 20892 USA.
RP Brennan, P (reprint author), Int Agcy Res Canc, 150 Cours Albert Thomas, F-69372 Lyon 08, France.
EM gep@iarc.fr
RI Waterboer, Tim/G-1252-2010; Grioni, Sara/K-5320-2016; Weiderpass,
Elisabete/M-4029-2016; Castellsague Pique, Xavier/N-5795-2014
OI Grioni, Sara/0000-0002-5891-8426; Weiderpass,
Elisabete/0000-0003-2237-0128; Sacerdote, Carlotta/0000-0002-8008-5096;
Healy, Claire M/0000-0001-7940-4611; Pawlita,
Michael/0000-0002-4720-8306; Ahrens, Wolfgang/0000-0003-3777-570X;
Castellsague Pique, Xavier/0000-0002-0802-3595
FU European Commission's 5th Framework Program [QLK1-2001-00182]; Europe
Against Cancer Program of the European Commission (SANCO); Deutsche
Krebshilfe; Deutsches Krebsforschungszentrum; German Federal Ministry of
Education and Research; Danish Cancer Society; Health Research Fund
(FIS) of the Spanish Ministry of Health; Spanish Regional Government of
Andalucia; Spanish Regional Government of Asturias; Spanish Regional
Government of Basque Country; Spanish Regional Government of Murcia;
Spanish Regional Government of Navarra; Catalan Institute of Oncology,
Spain; ISCIII of the Spanish Ministry of Health [RETICC DR06/0020];
Cancer Research UK; Medical Research Council, UK; Greek Ministry of
Health; Stavros Niarchos Foundation; Hellenic Health Foundation; Italian
Association for Research on Cancer (AIRC); Italian National Research
Council; Fondazione-IstitutoBanco Napoli, Italy; Associazione Italiana
per la Ricerca sul Cancro-AIRC Milan; Compagnia di San Paolo; Dutch
Ministry of Public Health, Welfare and Sports; World Cancer Research
Fund; Swedish Cancer Society; Swedish Scientific Council; Regional
Government of Vasterbotten, Sweden; NordForsk (Centre of excellence
programme HELGA), Norway; French League against Cancer (LNCC), France;
National Institute for Health and Medical Research (INSERM), France;
Mutuelle Generale de l'Education Nationale (MGEN), France; 3M Co,
France; Gustave Roussy Institute (IGR), France; General Councils of
France; National Cancer Institute Intramural Research Program; European
Commission [FP7-HEALTH-2011-282562]; Health General Directorate of the
French Social Affairs and Health Ministry
FX The ARCAGE study was supported by a grant from the European Commission's
5th Framework Program (contract QLK1-2001-00182). The EPIC study has
been supported by the Europe Against Cancer Program of the European
Commission (SANCO); Deutsche Krebshilfe, Deutsches
Krebsforschungszentrum, German Federal Ministry of Education and
Research; Danish Cancer Society; Health Research Fund (FIS) of the
Spanish Ministry of Health, Spanish Regional Governments of Andalucia,
Asturias, Basque Country, Murcia and Navarra; Catalan Institute of
Oncology, Spain; the ISCIII of the Spanish Ministry of Health (RETICC
DR06/0020); Cancer Research UK; Medical Research Council, UK; Greek
Ministry of Health; Stavros Niarchos Foundation; Hellenic Health
Foundation; Italian Association for Research on Cancer (AIRC); Italian
National Research Council, Fondazione-IstitutoBanco Napoli, Italy;
Associazione Italiana per la Ricerca sul Cancro-AIRC Milan; Compagnia di
San Paolo; Dutch Ministry of Public Health, Welfare and Sports; World
Cancer Research Fund; Swedish Cancer Society; Swedish Scientific
Council; Regional Government of Vasterbotten, Sweden; NordForsk (Centre
of excellence programme HELGA), Norway; French League against Cancer
(LNCC), France; National Institute for Health and Medical Research
(INSERM), France; Mutuelle Generale de l'Education Nationale (MGEN),
France; 3M Co, France; Gustave Roussy Institute (IGR), France; and
General Councils of France. The serology testing of EPIC prospective
study was supported by the National Cancer Institute Intramural Research
Program. The work done in this study was supported in part by a grant
from the European Commission's 7th Framework Program (contract
FP7-HEALTH-2011-282562) and partly by the Health General Directorate of
the French Social Affairs and Health Ministry.
NR 30
TC 1
Z9 1
U1 4
U2 5
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0300-5771
EI 1464-3685
J9 INT J EPIDEMIOL
JI Int. J. Epidemiol.
PD JUN
PY 2016
VL 45
IS 3
BP 752
EP 761
DI 10.1093/ije/dyw069
PG 10
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA DX8QG
UT WOS:000384653200029
PM 27197530
ER
PT J
AU Cai, H
Ye, F
Michel, A
Murphy, G
Sasazuki, S
Taylor, PR
Qiao, YL
Park, SK
Yoo, KY
Jee, SH
Cho, ER
Kim, J
Chen, SC
Abnet, CC
Tsugane, S
Cai, QY
Shu, XO
Zheng, W
Pawlita, M
Epplein, M
AF Cai, Hui
Ye, Fei
Michel, Angelika
Murphy, Gwen
Sasazuki, Shizuka
Taylor, Philip R.
Qiao, You-Lin
Park, Sue K.
Yoo, Keun-Young
Jee, Sun Ha
Cho, Eo Rin
Kim, Jeongseon
Chen, Sheau-Chiann
Abnet, Christian C.
Tsugane, Shoichiro
Cai, Qiuyin
Shu, Xiao-Ou
Zheng, Wei
Pawlita, Michael
Epplein, Meira
TI Helicobacter pylori blood biomarker for gastric cancer risk in East Asia
SO INTERNATIONAL JOURNAL OF EPIDEMIOLOGY
LA English
DT Article
DE Helicobacter pylori; stomach neoplasms; gastric cancer; biomarkers; East
Asia
ID PACIFIC CONSENSUS GUIDELINES; MULTIPLEX SEROLOGY; PREVENTION;
ANTIBODIES; INFECTION; ANTIGENS; PROTEINS; COHORT; HEALTH
AB Background: Incidence and mortality rates for gastric cancer, the fifth most commonly diagnosed and third most deadly cancer worldwide, are highest in East Asia. We sought to identify gastric cancer risk biomarkers among eight prospective studies from China, Japan and Korea.
Methods: This pooled nested case-control study included 1608 incident non-cardia gastric cancer cases and 1958 matched controls. Pre-diagnostic antibody levels to 15 Helicobacter pylori proteins were assessed using multiplex serology. Conditional logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs).
Results: Sero-positivity to 10 H. pylori antigens (Omp, CagA, VacA, HcpC, HP 0305, GroEL, NapA, HyuA, Cad, HpaA) was associated with a 1.29- to 3.26-fold increase in odds of gastric cancer. Omp and HP 0305 consistently remained associated with gastric cancer risk after mutually adjusting for all other markers. Sero-positivity to both Omp and HP 0305 was associated with an over 4-fold increase in gastric cancer incidence (OR, 4.09; 95% CI 3.26-5.13). When limited to only those who are CagA + H. pylori+, Omp/HP 0305 sero-positivity remained strongly associated with an over 3-fold increase in the odds of gastric cancer (OR, 3.34; 95% CI 2.27-4.91). The results were highly consistent among the cohorts.
Conclusions: We have confirmed new H. pylori biomarkers that are strongly associated with gastric cancer risk, even among those infected with the known H. pylori virulence factor CagA. These results may help to design cost-efficient prevention strategies to reduce gastric cancer incidence in East Asia.
C1 [Cai, Hui; Cai, Qiuyin; Shu, Xiao-Ou; Zheng, Wei; Epplein, Meira] Vanderbilt Univ, Med Ctr, Vanderbilt Epidemiol Ctr, 2525 West End Ave,6th Floor, Nashville, TN 37203 USA.
[Cai, Hui; Cai, Qiuyin; Shu, Xiao-Ou; Zheng, Wei; Epplein, Meira] Vanderbilt Univ, Med Ctr, Vanderbilt Ingram Canc Ctr, 2525 West End Ave,6th Floor, Nashville, TN 37203 USA.
[Ye, Fei; Chen, Sheau-Chiann] Vanderbilt Univ, Med Ctr, Vanderbilt Ctr Quantitat Sci, 2525 West End Ave,6th Floor, Nashville, TN 37203 USA.
[Michel, Angelika; Pawlita, Michael] German Canc Res Ctr DFKZ, Div Mol Diagnost Oncogen Infect, Heidelberg, Germany.
[Murphy, Gwen; Taylor, Philip R.; Abnet, Christian C.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Sasazuki, Shizuka; Tsugane, Shoichiro] Natl Canc Ctr, Epidemiol & Prevent Grp, Tokyo, Japan.
[Qiao, You-Lin] Chinese Acad Med Sci, Dept Canc Epidemiol, Beijing, Peoples R China.
[Qiao, You-Lin] Peking Union Med Coll, Beijing, Peoples R China.
[Park, Sue K.] Seoul Natl Univ, Coll Med, Dept Biomed Sci, Canc Res Inst, Seoul, South Korea.
[Park, Sue K.; Yoo, Keun-Young] Seoul Natl Univ, Coll Med, Dept Prevent Med, Seoul, South Korea.
[Jee, Sun Ha; Cho, Eo Rin] Yonsei Univ, Inst Hlth Promot, Dept Epidemiol & Hlth Promot, Seoul, South Korea.
[Kim, Jeongseon] Natl Canc Ctr, Res Inst, Div Canc Epidemiol & Prevent, Goyang, South Korea.
RP Epplein, M (reprint author), Vanderbilt Univ, Med Ctr, Div Epidemiol, 2525 West End Ave,6th Floor, Nashville, TN 37203 USA.
EM meira.epplein@vanderbilt.edu
RI Zheng, Wei/O-3351-2013; Waterboer, Tim/G-1252-2010; Abnet,
Christian/C-4111-2015
OI Zheng, Wei/0000-0003-1226-070X; Abnet, Christian/0000-0002-3008-7843
FU National Cancer Institute at the National Institutes of Health [R01
CA174853, K07 CA151782]
FX This work was supported by the National Cancer Institute at the National
Institutes of Health (R01 CA174853 and K07 CA151782 to M.E.). The
funders of the study had no role in study design; in the collection,
analysis or interpretation of the data; or in writing the report. M.E.
had full access to all study data and had final responsibility for the
decision to submit for publication.
NR 23
TC 1
Z9 1
U1 0
U2 0
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0300-5771
EI 1464-3685
J9 INT J EPIDEMIOL
JI Int. J. Epidemiol.
PD JUN
PY 2016
VL 45
IS 3
BP 774
EP 781
DI 10.1093/ije/dyw078
PG 8
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA DX8QG
UT WOS:000384653200031
PM 27170766
ER
PT J
AU Koutros, S
Silverman, DT
Alavanja, MCR
Andreotti, G
Lerro, CC
Heltshe, S
Lynch, CF
Sandler, DP
Blair, A
Freeman, LEB
AF Koutros, Stella
Silverman, Debra T.
Alavanja, Michael C. R.
Andreotti, Gabriella
Lerro, Catherine C.
Heltshe, Sonya
Lynch, Charles F.
Sandler, Dale P.
Blair, Aaron
Freeman, Laura E. Beane
TI Occupational exposure to pesticides and bladder cancer risk
SO INTERNATIONAL JOURNAL OF EPIDEMIOLOGY
LA English
DT Article
DE Pesticides; bladder cancer; epidemiology
ID AGRICULTURAL HEALTH; URINARY-BLADDER; PHENOXY HERBICIDES; DIESEL
EXHAUST; FARMERS; WORKERS; MEN; METAANALYSIS; MORTALITY; ETIOLOGY
AB Background: In the developed world, occupational exposures are a leading cause of bladder cancer. A few studies have suggested a link between pesticide exposures among agricultural populations and bladder cancer.
Methods: We used data from the Agricultural Health Study, a prospective cohort study which includes 57 310 pesticide applicators with detailed information on pesticide use, to evaluate the association between pesticides and bladder cancer. We used Poisson regression to calculate rate ratios (RRs) and 95% confidence intervals (CIs) to estimate the association between each of 65 pesticides and 321 incident bladder cancer cases which accrued over the course of follow-up (1993-2011), adjusting for lifestyle and demographic and nonpesticide farm-related exposures, including those previously linked to bladder cancer. We conducted additional analyses stratified by smoking status (never, former, current).
Results: We observed associations with bladder cancer risk for two imidazolinone herbicides, imazethapyr and imazaquin, which are aromatic amines. Ever use of imazaquin (RR = 1.54, 95% CI: 1.05, 2.26) was associated with increased risk whereas the excess risk among users of imazethapyr was evident among never smokers (RR in highest quartile vs non-exposed = 3.03, 95% CI: 1.46, 6.29, P-interaction = 0.005). We also observed increased risks overall and among never smokers for use of several chlorinated pesticides including chlorophenoxy herbicides and organochlorine insecticides.
Conclusions: Several associations between specific pesticides and bladder cancer risk were observed, many of which were stronger among never smokers, suggesting that possible risk factors for bladder cancer may be more readily detectable in those unexposed to potent risk factors like tobacco smoke.
C1 [Koutros, Stella; Silverman, Debra T.; Alavanja, Michael C. R.; Andreotti, Gabriella; Lerro, Catherine C.; Blair, Aaron; Freeman, Laura E. Beane] NCI, Div Canc Epidemiol & Genet, NIH, 9609 Med Ctr Dr, Bethesda, MD 20892 USA.
[Heltshe, Sonya] Univ Washington, Sch Med, Dept Pediat, Seattle Childrens Hosp,Res Inst, Seattle, WA 98195 USA.
[Lynch, Charles F.] Univ Iowa, Coll Publ Hlth, Iowa City, IA USA.
[Sandler, Dale P.] NIEHS, Epidemiol Branch, NIH, Res Triangle Pk, NC 27709 USA.
RP Koutros, S (reprint author), NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, 9609 Med Ctr Dr, Bethesda, MD 20892 USA.
EM KoutrosS@mail.nih.gov
RI Beane Freeman, Laura/C-4468-2015;
OI Beane Freeman, Laura/0000-0003-1294-4124; Sandler,
Dale/0000-0002-6776-0018
FU Intramural Research Program of the National Institutes of Health, NCI,
Division of Cancer Epidemiology and Genetics [Z01CP010119]; NIEHS
[Z01ES0490300]; Iowa Cancer Registry [HHSN261201300020I]; Iowa's Holden
Comprehensive Cancer Center [P30CA086862]; NIEHS-funded Environmental
Health Sciences Research Center at the University of Iowa [P30ES005605]
FX This work was supported by the Intramural Research Program of the
National Institutes of Health, NCI, Division of Cancer Epidemiology and
Genetics (Z01CP010119), NIEHS (Z01ES0490300), the Iowa Cancer Registry
(HHSN261201300020I) and Iowa's Holden Comprehensive Cancer Center
(P30CA086862) as well as the NIEHS-funded Environmental Health Sciences
Research Center at the University of Iowa (P30ES005605).
NR 49
TC 3
Z9 3
U1 7
U2 7
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0300-5771
EI 1464-3685
J9 INT J EPIDEMIOL
JI Int. J. Epidemiol.
PD JUN
PY 2016
VL 45
IS 3
BP 792
EP 805
DI 10.1093/ije/dyv195
PG 14
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA DX8QG
UT WOS:000384653200033
PM 26411407
ER
PT J
AU Berthiller, J
Straif, K
Agudo, A
Ahrens, W
dos Santos, AB
Boccia, S
Cadoni, G
Canova, C
Castellsague, X
Chen, C
Conway, D
Curado, MP
Dal Maso, L
Daudt, AW
Fabianova, E
Fernandez, L
Franceschi, S
Fukuyama, EE
Hayes, RB
Healy, C
Herrero, R
Holcatova, I
Kelsey, K
Kjaerheim, K
Koifman, S
Lagiou, P
La Vecchia, C
Lazarus, P
Levi, F
Lissowska, J
Macfarlane, T
Mates, D
McClean, M
Menezes, A
Merletti, F
Morgenstern, H
Muscat, J
Olshan, AF
Purdue, M
Ramroth, H
Rudnai, P
Schwartz, SM
Serraino, D
Shangina, O
Smith, E
Sturgis, EM
Szeszenia-Dabrowska, N
Thomson, P
Vaughan, TL
Vilensky, M
Wei, QY
Winn, DM
Wunsch-Filho, V
Zhang, ZF
Znaor, A
Ferro, G
Brennan, P
Boffetta, P
Hashibe, M
Lee, YCA
AF Berthiller, Julien
Straif, Kurt
Agudo, Antonio
Ahrens, Wolfgang
dos Santos, Alexandre Bezerra
Boccia, Stefania
Cadoni, Gabriella
Canova, Cristina
Castellsague, Xavier
Chen, Chu
Conway, David
Curado, Maria Paula
Dal Maso, Luigino
Daudt, Alexander W.
Fabianova, Eleonora
Fernandez, Leticia
Franceschi, Silvia
Fukuyama, Erica E.
Hayes, Richard B.
Healy, Claire
Herrero, Rolando
Holcatova, Ivana
Kelsey, Karl
Kjaerheim, Kristina
Koifman, Sergio
Lagiou, Pagona
La Vecchia, Carlo
Lazarus, Philip
Levi, Fabio
Lissowska, Jolanta
Macfarlane, Tatiana
Mates, Dana
McClean, Michael
Menezes, Ana
Merletti, Franco
Morgenstern, Hal
Muscat, Joshua
Olshan, Andrew F.
Purdue, Mark
Ramroth, Heribert
Rudnai, Peter
Schwartz, Stephen M.
Serraino, Diego
Shangina, Oxana
Smith, Elaine
Sturgis, Erich M.
Szeszenia-Dabrowska, Neonila
Thomson, Peter
Vaughan, Thomas L.
Vilensky, Marta
Wei, Qingyi
Winn, Deborah M.
Wunsch-Filho, Victor
Zhang, Zuo-Feng
Znaor, Ariana
Ferro, Gilles
Brennan, Paul
Boffetta, Paolo
Hashibe, Mia
Lee, Yuan-Chin Amy
TI Low frequency of cigarette smoking and the risk of head and neck cancer
in the INHANCE consortium pooled analysis
SO INTERNATIONAL JOURNAL OF EPIDEMIOLOGY
LA English
DT Article
DE Head and neck cancer; low frequency cigarette smoking; risk factors;
pooled analysis
ID EPIDEMIOLOGY CONSORTIUM; INTERNATIONAL HEAD; TOBACCO; ALCOHOL; TRACT
AB Background: Cigarette smoking is a major risk factor for head and neck cancer (HNC). To our knowledge, low cigarette smoking (<10 cigarettes per day) has not been extensively investigated in fine categories or among never alcohol drinkers.
Methods: We conducted a pooled analysis of individual participant data from 23 independent case-control studies including 19 660 HNC cases and 25 566 controls. After exclusion of subjects using other tobacco products including cigars, pipes, snuffed or chewed tobacco and straw cigarettes (tobacco product used in Brazil), as well as subjects smoking more than 10 cigarettes per day, 4093 HNC cases and 13 416 controls were included in the analysis. The lifetime average frequency of cigarette consumption was categorized as follows: never cigarette users, >0-3, >3-5, >5-10 cigarettes per day.
Results: Smoking >0-3 cigarettes per day was associated with a 50% increased risk of HNC in the study population [ odds ratio (OR) = 1.52, 95% confidence interval (CI): (1.21, 1.90). Smoking >3-5 cigarettes per day was associated in each subgroup from OR = 2.01 (95% CI: 1.22, 3.31) among never alcohol drinkers to OR = 2.74 (95% CI: 2.01, 3.74) among women and in each cancer site, particularly laryngeal cancer (OR = 3.48, 95% CI: 2.40, 5.05). However, the observed increased risk of HNC for low smoking frequency was not found among smokers with smoking duration shorter than 20 years.
Conclusion: Our results suggest a public health message that low frequency of cigarette consumption contributes to the development of HNC. However, smoking duration seems to play at least an equal or a stronger role in the development of HNC.
C1 [Berthiller, Julien; Straif, Kurt; Franceschi, Silvia; Herrero, Rolando; Ferro, Gilles; Brennan, Paul] Int Agcy Res Canc, Lyon, France.
[Berthiller, Julien] Hosp Civils Lyon, Pole Informat Med Evaluat Rech, Lyon, France.
[Agudo, Antonio; Castellsague, Xavier] Catalan Inst Oncol ICO IDIBELL, Barcelona, Spain.
[Ahrens, Wolfgang] Bremen Inst Prevent Res & Social Med BIPS, Bremen, Germany.
[dos Santos, Alexandre Bezerra; Fukuyama, Erica E.] Inst Canc Estado Sao Paulo ICESP, Sao Paulo, Brazil.
[Boccia, Stefania] Univ Cattolica Sacro Cuore, Sect Hyg, Inst Publ Hlth, Rome, Italy.
[Boccia, Stefania] Ist Ricovero & Cura Carattere Sci IRCCS, Rome, Italy.
[Cadoni, Gabriella] Univ Cattolica Sacro Cuore, Inst Otorhinolaryngol, Head & Neck Surg Dept, Rome, Italy.
[Canova, Cristina] Univ Padua, Padua, Italy.
[Castellsague, Xavier] CIBER Epidemiol & Salud Publ CIBERESP, Barcelona, Spain.
[Chen, Chu; Schwartz, Stephen M.; Vaughan, Thomas L.] Fred Hutchinson Canc Res Ctr, 1124 Columbia St, Seattle, WA 98104 USA.
[Conway, David] Univ Glasgow, Coll Med Vet & Life Sci, Sch Dent, Glasgow, Lanark, Scotland.
[Curado, Maria Paula] Int Prevent Res Inst, Lyon, France.
[Dal Maso, Luigino] Aviano Canc Ctr, Aviano, Italy.
[Daudt, Alexander W.] Hosp Clin Porto Alegre, Porto Alegre, RS, Brazil.
[Fabianova, Eleonora] Reg Author Publ Hlth, Banska Bystrica, Slovakia.
[Fernandez, Leticia] Inst Oncol & Radiobiol, Havana, Cuba.
[Hayes, Richard B.] NYU, Sch Med, Div Epidemiol, New York, NY USA.
[Healy, Claire] Trinity Coll Dublin, Sch Dent Sci, Dublin, Ireland.
[Holcatova, Ivana] Inst Hyg & Epidemiol, Prague, Czech Republic.
[Kelsey, Karl] Brown Univ, Providence, RI 02912 USA.
[Kjaerheim, Kristina] Canc Registry Norway, Oslo, Norway.
[Koifman, Sergio] Fundacao Oswaldo Cruz, Escola Nacl Saude Publ, Rio De Janeiro, Brazil.
[Lagiou, Pagona] Univ Athens, Sch Med, Athens, Greece.
[La Vecchia, Carlo] Ist Ricovero & Cura Carattere Sci IRCCS, Milan, Italy.
[Lazarus, Philip] Washington State Univ, Coll Pharm, Spokane, WA USA.
[Levi, Fabio] Lausanne Univ Hosp CHUV, Inst Social & Prevent Med IUMSP, Lausanne, Switzerland.
[Lissowska, Jolanta] M Skasodowska Curie Mem Canc Ctr, Warsaw, Poland.
[Lissowska, Jolanta] Inst Oncol, Dept Canc Epidemiol & Prevent, Warsaw, Poland.
[Macfarlane, Tatiana] Univ Aberdeen, Sch Dent, Aberdeen, Scotland.
[Mates, Dana] Natl Inst Publ Hlth, Bucharest, Romania.
[McClean, Michael] Boston Univ, Sch Publ Hlth, Boston, MA USA.
[Menezes, Ana] Univ Fed Pelotas, Pelotas, Brazil.
[Merletti, Franco] Univ Turin, Turin, Italy.
[Morgenstern, Hal] Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA.
[Morgenstern, Hal] Univ Michigan, Sch Publ Hlth, Dept Environm Hlth Sci, Ann Arbor, MI 48109 USA.
[Morgenstern, Hal] Univ Michigan, Sch Publ Hlth, Dept Urol, Ann Arbor, MI 48109 USA.
[Morgenstern, Hal] Univ Michigan, Sch Med, Ann Arbor, MI USA.
[Morgenstern, Hal] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA.
[Muscat, Joshua] Penn State Coll Med, Hershey, PA USA.
[Olshan, Andrew F.] UNC Sch Publ Hlth, Chapel Hill, NC USA.
[Purdue, Mark; Winn, Deborah M.] NICHHD, NIH, Bethesda, MD 20892 USA.
[Ramroth, Heribert] Heidelberg Univ, Heidelberg, Germany.
[Rudnai, Peter] Natl Inst Environm Hlth, Budapest, Hungary.
[Shangina, Oxana] Canc Res Ctr, Moscow, Russia.
[Smith, Elaine] Univ Iowa, Coll Publ Hlth, Iowa City, IA USA.
[Sturgis, Erich M.; Wei, Qingyi] UT MD Anderson Canc Ctr, Houston, TX USA.
[Szeszenia-Dabrowska, Neonila] Inst Occupat Med, Lodz, Poland.
[Thomson, Peter] Newcastle Univ, Newcastle Upon Tyne, Tyne & Wear, England.
[Vilensky, Marta] Univ Buenos Aires, Inst Oncol Angel H Roffo, Buenos Aires, DF, Argentina.
[Wunsch-Filho, Victor] Univ Sao Paulo, Sao Paulo, Brazil.
[Zhang, Zuo-Feng] Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA.
[Znaor, Ariana] Croatian Natl Canc Registry, Zagreb, Croatia.
[Boffetta, Paolo] Icahn Sch Med Mt Sinai, Tisch Canc Inst, New York, NY 10029 USA.
[Boffetta, Paolo] Icahn Sch Med Mt Sinai, Inst Translat Epidemiol, New York, NY 10029 USA.
[Hashibe, Mia] Univ Utah, Sch Med, Huntsman Canc Inst, 375 Chipeta Way, Salt Lake City, UT 84108 USA.
[Hashibe, Mia; Lee, Yuan-Chin Amy] Univ Utah, Sch Med, 375 Chipeta Way, Salt Lake City, UT 84108 USA.
RP Lee, YCA (reprint author), Univ Utah, Sch Med, Div Publ Hlth, Dept Family & Prevent Med, 375 Chipeta Way, Salt Lake City, UT 84108 USA.
EM amy.lee@utah.edu
RI Castellsague Pique, Xavier/N-5795-2014; Kowalski, Luiz/D-1701-2012;
Menezes, Ana/G-7266-2012; Curado, Maria Paula/M-6200-2013;
OI Castellsague Pique, Xavier/0000-0002-0802-3595; Kowalski,
Luiz/0000-0001-5865-9308; Healy, Claire M/0000-0001-7940-4611; Ahrens,
Wolfgang/0000-0003-3777-570X; Curado, Maria Paula/0000-0001-8172-2483;
dal maso, luigino/0000-0001-6163-200X; Macfarlane,
Tatiana/0000-0002-9392-0812; Serraino, Diego/0000-0003-0565-8920; La
Vecchia, Carlo/0000-0003-1441-897X; Hayes, Richard/0000-0002-0918-661X
FU National Cancer Institute [R03CA113157]; National Institute of Dental
and Craniofacial Research [R03DE016611]; Italian Association for
Research on Cancer [10068]; Italian Association for Research on Cancer
(AIRC); Italian League Against Cancer; Italian Ministry of Research;
Swiss League against Cancer; Swiss Research against Cancer/Oncosuisse
[KFS-700, OCS-1633]; World Cancer Research Fund; European Commission
INCO-COPERNICUS Program [IC15-CT98-0332]; National Institute of Health
[P01CA068384 K07CA104231, R01CA048996, R01DE012609, NIDCR R01DE011979,
NIDCR R01DE013110, FIRCA TW001500, R01CA061188, P01CA068384,
K07CA104231, R01DE013158, P50CA090388, R01DA011386, R03CA077954];
Veterans Affairs Merit Review Funds; National Institute of Environmental
Health Sciences [P30ES010126]; Alper Research Program for Environmental
Genomics of the UCLA Jonsson Comprehensive Cancer Center; National
Institutes of Health (NCI) US; NIDCR intramural programs; Fondo para la
Investigacion Cientifica y Tecnologica (FONCYT) Argentina; IMIM
(Barcelona); Fundaco de Amparo a Pesquisa no Estado de Sao Paulo
(FAPESP) [01/01768-2]; European Commission [IC18-CT97-0222]; Fondo de
Investigaciones Sanitarias (FIS) of the Spanish Government [FIS 97/0024,
FIS 97/0662, BAE 01/5013]; International Union Against Cancer (UICC);
Yamagiwa-Yoshida Memorial International Cancer Study Grant; AIRC
(Italian Agency for Research on Cancer); Intramural Program of the
National Cancer Institute, National Institute of Health, United States;
Fundacao de Ampara a Pesquisa no Estado de Sao Paulo (FAPESP)
[10/51168-0]; European Community (5th Frame work Programme)
[QLK1-CT-2001-00182]; German Ministry of Education and Research
[01GB9702/3]; NIH [T32CA009142, U01CA096134, R21ES011667, R01ES011740,
R01CA100264, R01CA078609, R01CA100679, R01CA051845, R01CA030022]
FX The pooled data coordination team (PBoffetta, MH, Y-CAL) were supported
by National Cancer Institute grant R03CA113157 and by National Institute
of Dental and Craniofacial Research grant R03DE016611r The Milan study
(CLV) was supported by the Italian Association for Research on Cancer
(Grant no. 10068).r The Aviano study (LDM) was supported by a grant from
the Italian Association for Research on Cancer (AIRC), Italian League
Against Cancer and Italian Ministry of Researchr The Italy Multicenter
study (DS) was supported by the Italian Association for Research on
Cancer (AIRC), Italian League Against Cancer and Italian Ministry of
Research.r The Study from Switzerland (FL) was supported by the Swiss
League against Cancer and the Swiss Research against Cancer/Oncosuisse
[KFS-700, OCS-1633].r The central Europe study (PBoffetta, PBrenan, EF,
JL, DM, PR, OS, NS-D) was supported by the World Cancer Research Fund
and the European Commission INCO-COPERNICUS Program [Contract No.
IC15-CT98-0332]r The New York multicentre study (JM) was supported by a
grant from National Institute of Health [P01CA068384 K07CA104231].r The
study from the Fred Hutchison Cancer Research Center from Seattle (CC,
SMS) was supported by a National Institute of Health grant [R01CA048996,
R01DE012609].r The Iowa study (ES) was supported by National Institute
of Health [NIDCR R01DE011979, NIDCR R01DE013110, FIRCA TW001500] and
Veterans Affairs Merit Review Funds.r The North Carolina studies (AFO)
were supported by National Institute of Health [R01CA061188], and in
part by a grant from the National Institute of Environmental Health
Sciences [P30ES010126].r The Tampa study (PLazarus, JM) was supported by
National Institute of Health grants [P01CA068384, K07CA104231,
R01DE013158]r The Los Angeles study (Z-F Z, HM) was supported by grants
from National Institute of Health [P50CA090388, R01DA011386,
R03CA077954, T32CA009142, U01CA096134, R21ES011667] and the Alper
Research Program for Environmental Genomics of the UCLA Jonsson
Comprehensive Cancer Center.r The Houston study (EMS, GL) was supported
by a grant from National Institute of Health [R01ES011740,
R01CA100264].r The Puerto Rico study (RBH, MPP) was supported by a grant
from National Institutes of Health (NCI) US and NIDCR intramural
programs.r The Latin America study (PBoffetta, PBrenan, MV, LF, MPC, AM,
AWD, SK, VW-F) was supported by Fondo para la Investigacion Cientifica y
Tecnologica (FONCYT) Argentina, IMIM (Barcelona), Fundaco de Amparo a
Pesquisa no Estado de Sao Paulo (FAPESP) [No 01/01768-2], and European
Commission [IC18-CT97-0222]r The IARC multicentre study (SF, RH, XC) was
supported by Fondo de Investigaciones Sanitarias (FIS) of the Spanish
Government [FIS 97/0024, FIS 97/0662, BAE 01/5013], International Union
Against Cancer (UICC), and Yamagiwa-Yoshida Memorial International
Cancer Study Grant.r The Boston study (KKelsey, MMcC) was supported by a
grant from National Institute of Health [R01CA078609, R01CA100679].r The
Rome study (SB, GC) was supported by AIRC (Italian Agency for Research
on Cancer).r The US multicentre study (BW) was supported by The
Intramural Program of the National Cancer Institute, National Institute
of Health, United States.r The Sao Paolo study (V W-F) was supported by
Fundacao de Ampara a Pesquisa no Estado de Sao Paulo (FAPESP No
10/51168-0)r The MSKCC study (SS, G-P Y) was supported by a grant from
National Institute of Health [R01CA051845].; r The Seattle-Leo stud (FV)
was supported by a grant from National Institute of Health
[R01CA030022]r The western Europe Study (PBoffetta, IH, WA, PLagiou, DS,
LS, FM, CH, KKjaerheim, DC, TMc, PT, AA, AZ) was supported by European
Community (5th Frame work Programme) grant no QLK1-CT-2001-00182.r The
Germany Heidelberg study (HR) was supported by the grant No. 01GB9702/3
from the German Ministry of Education and Research.
NR 14
TC 3
Z9 3
U1 5
U2 5
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0300-5771
EI 1464-3685
J9 INT J EPIDEMIOL
JI Int. J. Epidemiol.
PD JUN
PY 2016
VL 45
IS 3
BP 835
EP 845
DI 10.1093/ije/dyv146
PG 11
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA DX8QG
UT WOS:000384653200037
PM 26228584
ER
PT J
AU Freedman, ND
Abnet, CC
Caporaso, NE
Fraumeni, JF
Murphy, G
Hartge, P
Hollenbeck, AR
Park, Y
Shiels, MS
Silverman, DT
AF Freedman, Neal D.
Abnet, Christian C.
Caporaso, Neil E.
Fraumeni, Joseph F., Jr.
Murphy, Gwen
Hartge, Patricia
Hollenbeck, Albert R.
Park, Yikyung
Shiels, Meredith S.
Silverman, Debra T.
TI Impact of changing US cigarette smoking patterns on incident cancer:
risks of 20 smoking-related cancers among the women and men of the
NIH-AARP cohort
SO INTERNATIONAL JOURNAL OF EPIDEMIOLOGY
LA English
DT Article
DE Cigarette smoking; cohort; cancer; men and women
ID UNITED-STATES; LUNG-CANCER; BLADDER-CANCER; MORTALITY; ASSOCIATION;
ALCOHOL; TOBACCO; SMOKERS; DESIGN; ADULTS
AB Background: Historically, US women started smoking at a later age than men and had lower relative risks for smoking-related cancers. However, more recent birth cohorts of women and men have similar smoking histories and have now reached the high-risk age for cancer. The impact of these changes on cancer incidence has not been systematically examined.
Methods: Relative risks (RR), 95% confidence intervals (CI) and attributable fractions were calculated for cigarette smoking and incidence of 20 smoking-related cancers in 186 057 women and 266 074 men of the National Institutes of Health-AARP cohort, aged 50 to 71 years in 1995 and followed for 11 years.
Results: In the cohort, which included participants born between 1924 and 1945, most women and men started smoking as teenagers. RRs for current vs never smoking were similar in women and men for the following cancers: lung squamous-cell (RR women: 121.4, 95% CI: 57.3-257.4; RR men: 114.6, 95% CI: 61.2-214.4), lung adenocarcinoma (RR women: 11.7, 95% CI: 9.8-14.0; RR men: 15.6, 95% CI: 12.5-19.6), laryngeal (RR women: 37.0, 95% CI: 14.9-92.3; RR men: 13.8, 95% CI: 9.3-20.2), oral cavity-pharyngeal (RR women: 4.4, 95% CI: 3.3-6.0; RR men: 3.8, 95% CI: 3.0-4.7), oesophageal squamous cell (RR women: 7.3, 95% CI: 3.5-15.5; RR men: 6.2, 95% CI: 2.8-13.7), bladder (RR women: 4.7, 95% CI: 3.7-5.8; RR men: 4.0, 95% CI: 3.5-4.5), colon (RR women: 1.3, 95% CI: 1.2-1.5; RR men: 1.3, 95% CI: 1.1-1.4), and at other sites, with similar attributable fractions.
Conclusions: RRs for current smoking and incidence of many smoking-related cancers are now similar in US women and men, likely reflecting converging smoking patterns.
C1 [Freedman, Neal D.; Abnet, Christian C.; Caporaso, Neil E.; Fraumeni, Joseph F., Jr.; Murphy, Gwen; Hartge, Patricia; Shiels, Meredith S.; Silverman, Debra T.] NCI, Div Canc Epidemiol & Genet, Rockville, MD USA.
[Hollenbeck, Albert R.] AARP, Washington, DC USA.
[Park, Yikyung] Washington Univ, Sch Med St Louis, Div Publ Hlth Sci, St Louis, MO USA.
RP Freedman, ND (reprint author), NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, 9609 Med Ctr Dr,MSC9768, Bethesda, MD 20892 USA.
EM freedmanne@mail.nih.gov
RI Abnet, Christian/C-4111-2015
OI Abnet, Christian/0000-0002-3008-7843
FU National Institutes of Health, National Cancer Institute, Division of
Cancer Epidemiology and Genetics
FX This work was supported by the Intramural Research Program of the
National Institutes of Health, National Cancer Institute, Division of
Cancer Epidemiology and Genetics.
NR 31
TC 2
Z9 2
U1 2
U2 2
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0300-5771
EI 1464-3685
J9 INT J EPIDEMIOL
JI Int. J. Epidemiol.
PD JUN
PY 2016
VL 45
IS 3
BP 846
EP 856
DI 10.1093/ije/dyv175
PG 11
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA DX8QG
UT WOS:000384653200038
PM 26411408
ER
PT J
AU Dixon, SC
Nagle, CM
Thrift, AP
Pharoah, PDP
Pearce, CL
Zheng, W
Painter, JN
Chenevix-Trench, G
Fasching, PA
Beckmann, MW
Lambrechts, D
Vergote, I
Lambrechts, S
Van Nieuwenhuysen, E
Rossing, MA
Doherty, JA
Wicklund, KG
Chang-Claude, J
Rudolph, A
Moysich, KB
Odunsi, K
Goodman, MT
Wilkens, LR
Thompson, PJ
Shvetsov, YB
Dork, T
Park-Simon, TW
Hillemanns, P
Bogdanova, N
Butzow, R
Nevanlinna, H
Pelttari, LM
Leminen, A
Modugno, F
Ness, RB
Edwards, RP
Kelley, JL
Heitz, F
Karlan, BY
Kjaer, SK
Hogdall, E
Jensen, A
Goode, EL
Fridley, BL
Cunningham, JM
Winham, SJ
Giles, GG
Bruinsma, F
Milne, RL
Southey, MC
Hildebrandt, MAT
Wu, XF
Lu, KH
Liang, D
Levine, DA
Bisogna, M
Schildkraut, JM
Berchuck, A
Cramer, DW
Terry, KL
Bandera, EV
Olson, SH
Salvesen, HB
Thomsen, LC
Kopperud, RK
Bjorge, L
Kiemeney, LA
Massuger, LFAG
Pejovic, T
Cook, LS
Le, ND
Swenerton, KD
Brooks-Wilson, A
Kelemen, LE
Lubinski, J
Huzarski, T
Gronwald, J
Menkiszak, J
Wentzensen, N
Brinton, L
Yang, H
Lissowska, J
Hogdall, CK
Lundvall, L
Song, HL
Tyrer, JP
Campbell, I
Eccles, D
Paul, J
Glasspool, R
Siddiqui, N
Whittemore, AS
Sieh, W
McGuire, V
Rothstein, JH
Narod, SA
Phelan, C
Risch, HA
McLaughlin, JR
Anton-Culver, H
Ziogas, A
Menon, U
Gayther, SA
Ramus, SJ
Gentry-Maharaj, A
Wu, AH
Pike, MC
Tseng, CC
Kupryjanczyk, J
Dansonka-Mieszkowska, A
Budzilowska, A
Spiewankiewicz, B
Webb, PM
AF Dixon, Suzanne C.
Nagle, Christina M.
Thrift, Aaron P.
Pharoah, Paul D. P.
Pearce, Celeste Leigh
Zheng, Wei
Painter, Jodie N.
Chenevix-Trench, Georgia
Fasching, Peter A.
Beckmann, Matthias W.
Lambrechts, Diether
Vergote, Ignace
Lambrechts, Sandrina
Van Nieuwenhuysen, Els
Rossing, Mary Anne
Doherty, Jennifer A.
Wicklund, Kristine G.
Chang-Claude, Jenny
Rudolph, Anja
Moysich, Kirsten B.
Odunsi, Kunle
Goodman, Marc T.
Wilkens, Lynne R.
Thompson, Pamela J.
Shvetsov, Yurii B.
Doerk, Thilo
Park-Simon, Tjoung-Won
Hillemanns, Peter
Bogdanova, Natalia
Butzow, Ralf
Nevanlinna, Heli
Pelttari, Liisa M.
Leminen, Arto
Modugno, Francesmary
Ness, Roberta B.
Edwards, Robert P.
Kelley, Joseph L.
Heitz, Florian
Karlan, Beth Y.
Kjaer, Susanne K.
Hogdall, Estrid
Jensen, Allan
Goode, Ellen L.
Fridley, Brooke L.
Cunningham, Julie M.
Winham, Stacey J.
Giles, Graham G.
Bruinsma, Fiona
Milne, Roger L.
Southey, Melissa C.
Hildebrandt, Michelle A. T.
Wu, Xifeng
Lu, Karen H.
Liang, Dong
Levine, Douglas A.
Bisogna, Maria
Schildkraut, Joellen M.
Berchuck, Andrew
Cramer, Daniel W.
Terry, Kathryn L.
Bandera, Elisa V.
Olson, Sara H.
Salvesen, Helga B.
Thomsen, Liv Cecilie
Kopperud, Reidun K.
Bjorge, Line
Kiemeney, Lambertus A.
Massuger, Leon F. A. G.
Pejovic, Tanja
Cook, Linda S.
Le, Nhu D.
Swenerton, Kenneth D.
Brooks-Wilson, Angela
Kelemen, Linda E.
Lubinski, Jan
Huzarski, Tomasz
Gronwald, Jacek
Menkiszak, Janusz
Wentzensen, Nicolas
Brinton, Louise
Yang, Hannah
Lissowska, Jolanta
Hogdall, Claus K.
Lundvall, Lene
Song, Honglin
Tyrer, Jonathan P.
Campbell, Ian
Eccles, Diana
Paul, James
Glasspool, Rosalind
Siddiqui, Nadeem
Whittemore, Alice S.
Sieh, Weiva
McGuire, Valerie
Rothstein, Joseph H.
Narod, Steven A.
Phelan, Catherine
Risch, Harvey A.
McLaughlin, John R.
Anton-Culver, Hoda
Ziogas, Argyrios
Menon, Usha
Gayther, Simon A.
Ramus, Susan J.
Gentry-Maharaj, Aleksandra
Wu, Anna H.
Pike, Malcolm C.
Tseng, Chiu-Chen
Kupryjanczyk, Jolanta
Dansonka-Mieszkowska, Agnieszka
Budzilowska, Agnieszka
Spiewankiewicz, Beata
Webb, Penelope M.
CA AOCS Grp
Australian Canc Study Ovarian Canc
Ovarian Canc Assoc Consortium
TI Adult body mass index and risk of ovarian cancer by subtype: a Mendelian
randomization study
SO INTERNATIONAL JOURNAL OF EPIDEMIOLOGY
LA English
DT Article
DE Body mass index; obesity; ovarian neoplasms; Mendelian randomization
analysis
ID METAANALYSIS; REGRESSION; OBESITY; SUSCEPTIBILITY; INSTRUMENTS
AB Background: Observational studies have reported a positive association between body mass index (BMI) and ovarian cancer risk. However, questions remain as to whether this represents a causal effect, or holds for all histological subtypes. The lack of association observed for serous cancers may, for instance, be due to disease-associated weight loss. Mendelian randomization (MR) uses genetic markers as proxies for risk factors to overcome limitations of observational studies. We used MR to elucidate the relationship between BMI and ovarian cancer, hypothesizing that genetically predicted BMI would be associated with increased risk of non-high grade serous ovarian cancers (non-HGSC) but not HGSC.
Methods: We pooled data from 39 studies (14 047 cases, 23 003 controls) in the Ovarian Cancer Association Consortium. We constructed a weighted genetic risk score (GRS, partial F-statistic = 172), summing alleles at 87 single nucleotide polymorphisms previously associated with BMI, weighting by their published strength of association with BMI. Applying two-stage predictor-substitution MR, we used logistic regression to estimate study-specific odds ratios (OR) and 95% confidence intervals (CI) for the association between genetically predicted BMI and risk, and pooled these using random-effects metaanalysis.
Results: Higher genetically predicted BMI was associated with increased risk of non-HGSC (pooled OR = 1.29, 95% CI 1.03-1.61 per 5 units BMI) but not HGSC (pooled OR = 1.06, 95% CI 0.88-1.27). Secondary analyses stratified by behaviour/subtype suggested that, consistent with observational data, the association was strongest for low-grade/borderline serous cancers (OR = 1.93, 95% CI 1.33-2.81).
Conclusions: Our data suggest that higher BMI increases risk of non-HGSC, but not the more common and aggressive HGSC subtype, confirming the observational evidence.
C1 [Dixon, Suzanne C.; Nagle, Christina M.; Webb, Penelope M.] QIMR Berghofer Med Res Inst, Gynaecol Canc Grp, Brisbane, Qld, Australia.
[Dixon, Suzanne C.; Nagle, Christina M.; Webb, Penelope M.] Univ Queensland, Sch Publ Hlth, Brisbane, Qld, Australia.
[Thrift, Aaron P.] Baylor Coll Med, Dept Med, Houston, TX 77030 USA.
[Thrift, Aaron P.] Baylor Coll Med, Dan L Duncan Canc Ctr, Houston, TX 77030 USA.
[Pharoah, Paul D. P.] Univ Cambridge, Ctr Canc Genet Epidemiol, Cambridge, England.
[Pearce, Celeste Leigh] Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA.
[Pearce, Celeste Leigh; Gayther, Simon A.; Ramus, Susan J.; Wu, Anna H.; Tseng, Chiu-Chen] Univ Southern Calif, Keck Sch Med, Dept Prevent Med, Norris Comprehens Canc Ctr, Los Angeles, CA USA.
[Zheng, Wei] Vanderbilt Univ, Sch Med, Vanderbilt Epidemiol Ctr, Nashville, TN 37212 USA.
[Painter, Jodie N.] QIMR Berghofer Med Res Inst, Mol Canc Epidemiol Grp, Brisbane, Qld, Australia.
[Chenevix-Trench, Georgia] QIMR Berghofer Med Res Inst, Canc Genet Grp, Brisbane, Qld, Australia.
[Fasching, Peter A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Hematol & Oncol, Los Angeles, CA 90095 USA.
[Fasching, Peter A.; Beckmann, Matthias W.] Univ Erlangen Nurnberg, Comprehens Canc Ctr Erlangen Nuremberg, Dept Gynecol & Obstet, Univ Hosp Erlangen, Erlangen, Germany.
[Lambrechts, Diether] VIB, Vesalius Res Ctr, Leuven, Belgium.
[Lambrechts, Diether] Univ Leuven, Dept Oncol, Lab Translat Genet, Leuven, Belgium.
[Vergote, Ignace; Lambrechts, Sandrina; Van Nieuwenhuysen, Els] Univ Hosp Leuven, Dept Obstet & Gynaecol, Div Gynecol Oncol, Leuven, Belgium.
[Vergote, Ignace; Lambrechts, Sandrina; Van Nieuwenhuysen, Els] Univ Hosp Leuven, Leuven Canc Inst, Leuven, Belgium.
[Rossing, Mary Anne; Wicklund, Kristine G.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Program Epidemiol, 1124 Columbia St, Seattle, WA 98104 USA.
[Rossing, Mary Anne] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
[Doherty, Jennifer A.] Geisel Sch Med Dartmouth, Dept Epidemiol, Hanover, NH USA.
[Chang-Claude, Jenny; Rudolph, Anja] German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany.
[Moysich, Kirsten B.] Roswell Pk Canc Inst, Dept Canc Prevent & Control, Buffalo, NY 14263 USA.
[Odunsi, Kunle] Roswell Pk Canc Inst, Dept Gynecol Oncol, Buffalo, NY 14263 USA.
[Goodman, Marc T.; Thompson, Pamela J.] Cedars Sinai Med Ctr, Canc Prevent & Control, Samuel Oschin Comprehens Canc Inst, Los Angeles, CA 90048 USA.
[Goodman, Marc T.] Cedars Sinai Med Ctr, Dept Biomed Sci, Community & Populat Hlth Res Inst, Los Angeles, CA 90048 USA.
[Wilkens, Lynne R.; Shvetsov, Yurii B.] Univ Hawaii, Ctr Canc, Canc Epidemiol Program, Honolulu, HI 96822 USA.
[Doerk, Thilo; Park-Simon, Tjoung-Won; Hillemanns, Peter] Hannover Med Sch, Clin Obstet, Hannover, Germany.
[Doerk, Thilo; Park-Simon, Tjoung-Won; Hillemanns, Peter] Hannover Med Sch, Clin Gynaecol, Hannover, Germany.
[Bogdanova, Natalia] Hannover Med Sch, Radiat Oncol Res Unit, Hannover, Germany.
[Butzow, Ralf] Univ Helsinki, Dept Pathol, Helsinki, Finland.
[Butzow, Ralf; Nevanlinna, Heli; Pelttari, Liisa M.; Leminen, Arto] Helsinki Univ Hosp, Helsinki, Finland.
[Nevanlinna, Heli; Pelttari, Liisa M.; Leminen, Arto] Univ Helsinki, Dept Obstet & Gynecol, Helsinki, Finland.
[Modugno, Francesmary; Edwards, Robert P.; Kelley, Joseph L.] Univ Pittsburgh, Sch Med, Dept Obstet Gynecol & Reprod Sci, Div Gynecol Oncol, Pittsburgh, PA USA.
[Modugno, Francesmary; Edwards, Robert P.] Magee Womens Res Inst, Womens Canc Res Program, Ovarian Canc Ctr Excellence, Pittsburgh, PA USA.
[Modugno, Francesmary; Edwards, Robert P.] Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA.
[Modugno, Francesmary] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA.
[Ness, Roberta B.] Univ Texas Sch Publ Hlth, Houston, TX USA.
[Heitz, Florian] Knappschaft GmbH, Evang Huyssens Stiftung, Kliniken Essen Mitte, Dept Gynecol & Gynecol Oncol, Essen, Germany.
[Heitz, Florian] Dr Horst Schmidt Kliniken Wiesbaden, Dept Gynecol & Gynecol Oncol, Wiesbaden, Germany.
[Karlan, Beth Y.] Cedars Sinai Med Ctr, Womens Canc Program, Samuel Oschin Comprehens Canc Inst, Los Angeles, CA 90048 USA.
[Kjaer, Susanne K.; Hogdall, Estrid; Jensen, Allan] Danish Canc Soc Res Ctr, Dept Virus Lifestyle & Genes, Copenhagen, Denmark.
[Kjaer, Susanne K.; Hogdall, Claus K.; Lundvall, Lene] Univ Copenhagen, Rigshosp, Dept Gynaecol, Copenhagen, Denmark.
[Hogdall, Estrid] Univ Copenhagen, Herlev Hosp, Dept Pathol, Mol Unit, Copenhagen, Denmark.
[Goode, Ellen L.] Mayo Clin, Div Epidemiol, Dept Hlth Sci Res, Rochester, MN USA.
[Fridley, Brooke L.] Univ Kansas, Med Ctr, Kansas City, KS 66103 USA.
[Cunningham, Julie M.] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA.
[Winham, Stacey J.] Mayo Clin, Div Biomed Stat & Informat, Dept Hlth Sci Res, Rochester, MN USA.
[Giles, Graham G.; Bruinsma, Fiona; Milne, Roger L.] Canc Council Victoria, Canc Epidemiol Ctr, Melbourne, Vic, Australia.
[Giles, Graham G.; Milne, Roger L.] Univ Melbourne, Melbourne Sch Populat & Global Hlth, Ctr Epidemiol & Biostat, Melbourne, Vic, Australia.
[Giles, Graham G.] Monash Univ, Dept Epidemiol & Prevent Med, Melbourne, Vic, Australia.
[Southey, Melissa C.] Univ Melbourne, Dept Pathol, Genet Epidemiol Lab, Melbourne, Vic, Australia.
[Hildebrandt, Michelle A. T.; Wu, Xifeng] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA.
[Lu, Karen H.] Univ Texas MD Anderson Canc Ctr, Dept Gynecol Oncol, Houston, TX 77030 USA.
[Liang, Dong] Texas Southern Univ, Coll Pharm & Hlth Sci, Houston, TX USA.
[Levine, Douglas A.; Bisogna, Maria] Mem Sloan Kettering Canc Ctr, Dept Surg, Gynecol Serv, New York, NY 10021 USA.
[Schildkraut, Joellen M.] Duke Univ, Med Ctr, Dept Community & Family Med, Durham, NC 27710 USA.
[Schildkraut, Joellen M.] Duke Canc Inst, Canc Control & Populat Sci, Durham, NC USA.
[Berchuck, Andrew] Duke Univ, Med Ctr, Dept Obstet & Gynecol, Durham, NC 27710 USA.
[Cramer, Daniel W.; Terry, Kathryn L.] Brigham & Womens Hosp, Obstet & Gynecol Epidemiol Ctr, 75 Francis St, Boston, MA 02115 USA.
[Bandera, Elisa V.] Rutgers Canc Inst New Jersey, Canc Prevent & Control Program, New Brunswick, NJ USA.
[Olson, Sara H.; Pike, Malcolm C.] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA.
[Salvesen, Helga B.; Thomsen, Liv Cecilie; Kopperud, Reidun K.; Bjorge, Line] Haukeland Hosp, Dept Gynecol & Obstet, Bergen, Norway.
[Salvesen, Helga B.; Thomsen, Liv Cecilie; Kopperud, Reidun K.; Bjorge, Line] Univ Bergen, Dept Clin Sci, Ctr Canc Biomarkers, Bergen, Norway.
[Kiemeney, Lambertus A.] Radboud Univ Nijmegen, Med Ctr, Radboud Inst Hlth Sci, Nijmegen, Netherlands.
[Massuger, Leon F. A. G.] Radboud Univ Nijmegen, Med Ctr, Radboud Inst Mol Life Sci, Dept Gynaecol, Nijmegen, Netherlands.
[Pejovic, Tanja] Oregon Hlth & Sci Univ, Dept Obstet & Gynecol, Portland, OR 97201 USA.
[Pejovic, Tanja] Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97201 USA.
[Cook, Linda S.] Univ New Mexico, Div Epidemiol & Biostat, Dept Internal Med, Albuquerque, NM 87131 USA.
[Le, Nhu D.] BC Canc Agcy, Canc Control Res, Vancouver, BC, Canada.
[Swenerton, Kenneth D.] Univ British Columbia, Dept Med, Vancouver, BC, Canada.
[Brooks-Wilson, Angela] BC Canc Agcy, Canadas Michael Smith Genome Sci Ctr, Vancouver, BC, Canada.
[Brooks-Wilson, Angela] Simon Fraser Univ, Dept Biomed Physiol & Kinesiol, Burnaby, BC, Canada.
[Kelemen, Linda E.] Med Univ South Carolina, Dept Publ Hlth Sci, Charleston, SC USA.
[Lubinski, Jan; Huzarski, Tomasz; Gronwald, Jacek] Pomeranian Med Univ, Dept Genet & Pathol, Int Hereditary Canc Ctr, Szczecin, Poland.
[Menkiszak, Janusz] Pomeranian Med Univ, Dept Gynecol Surg & Gynecol Oncol Adults & Adoles, Szczecin, Poland.
[Wentzensen, Nicolas; Brinton, Louise; Yang, Hannah] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Lissowska, Jolanta] Maria Sklodowska Curie Mem Canc Ctr & Inst Oncol, Dept Canc Epidemiol & Prevent, Warsaw, Poland.
[Song, Honglin; Tyrer, Jonathan P.] Univ Cambridge, Dept Oncol, Strangeways Res Lab, Cambridge, England.
[Campbell, Ian] Peter MacCallum Canc Ctr, Div Res, Canc Genet Lab, Melbourne, Vic, Australia.
[Campbell, Ian] Univ Melbourne, Dept Pathol, Parkville, Vic, Australia.
[Eccles, Diana] Univ Southampton, Fac Med, Southampton, Hants, England.
[Paul, James; Glasspool, Rosalind] Beatson West Scotland Canc Ctr, Glasgow, Lanark, Scotland.
[Siddiqui, Nadeem] Glasgow Royal Infirm, Dept Gynaecol Oncol, Glasgow, Lanark, Scotland.
[Whittemore, Alice S.; Sieh, Weiva; McGuire, Valerie; Rothstein, Joseph H.] Stanford Univ, Sch Med, Dept Hlth Res & Policy Epidemiol, Stanford, CA 94305 USA.
[Narod, Steven A.] Univ Toronto, Womens Coll, Res Inst, Toronto, ON, Canada.
[Phelan, Catherine] H Lee Moffitt Canc Ctr & Res Inst, Dept Canc Epidemiol, Tampa, FL USA.
[Risch, Harvey A.] Yale Sch Publ Hlth, Dept Chron Dis Epidemiol, New Haven, CT USA.
[McLaughlin, John R.] Publ Hlth Ontario, Toronto, ON, Canada.
[Anton-Culver, Hoda; Ziogas, Argyrios] Univ Calif Irvine, Dept Epidemiol, Irvine, CA USA.
[Anton-Culver, Hoda] Univ Calif Irvine, Sch Med, UCI Ctr Canc Genet Res & Prevent, Genet Epidemiol Res Inst, Irvine, CA 92717 USA.
[Menon, Usha; Gentry-Maharaj, Aleksandra] UCL, Inst Womens Hlth, Womens Canc, London, England.
[Kupryjanczyk, Jolanta; Dansonka-Mieszkowska, Agnieszka; Budzilowska, Agnieszka] Maria Sklodowska Curie Mem Canc Ctr & Inst Oncol, Dept Pathol & Lab Diagnost, Warsaw, Poland.
[Spiewankiewicz, Beata] Maria Sklodowska Curie Mem Canc Ctr & Inst Oncol, Dept Gynecol Oncol, Warsaw, Poland.
RP Dixon, SC (reprint author), Royal Brisbane Hosp, QIMR Berghofer Med Res Inst, Gynaecol Canc Grp, Locked Bag 2000, Herston, Qld 4029, Australia.
EM Suzanne.Dixon@qimrberghofer.edu.au
RI Menkiszak, Janusz/I-4036-2014; Zheng, Wei/O-3351-2013; Gronwald,
Jacek/A-4576-2017; Dork, Thilo/J-8620-2012; Bjorge, Line/C-1307-2017;
salvesen, Helga/C-1187-2017; Brooks-Wilson, Angela/E-9399-2012;
OI Zheng, Wei/0000-0003-1226-070X; Gronwald, Jacek/0000-0002-3643-2871;
Bjorge, Line/0000-0002-0240-2770; salvesen, Helga/0000-0002-4438-8831;
Brooks-Wilson, Angela/0000-0003-1009-6408; Winham,
Stacey/0000-0002-8492-9102
FU National Cancer Institute at the U.S. National Institutes of Health
[K07-CA095666, K07-CA80668, K07-CA143047, K22-CA138563, N01-CN025403,
N01-CN55424, N01-PC67001, N01-PC67010, P01-CA17054, P30-CA072720,
P30-CA008748, P30-CA14089, P30-CA15083, P50-CA105009, P50-CA136393,
P50-CA159981, R01-CA058860, R01 CA063678, R01 CA063682, R01-CA092044,
R01-CA095023, R01-CA16056, R01-CA54419, R01-CA58598, R01-CA61107,
R01-CA61132, R01-CA76016, R01-CA83918, R01-CA87538, R01-CA112523,
R01-CA122443, R03-CA113148, R03-CA115195, U01-CA69417, U01-CA71966];
European Commission [223175 HEALTH F2 2009-223175]; Cancer Research UK
[C490/A16561, C536/A13086, C536/A6689, C1287/A10118, C1287/A 10710,
C12292/A11174, C1281/A12014, C5047/A8384, C5047/A15007, C5047/A10692,
C8197/A16565]; National Institutes of Health [CA128978]; Cancer
Post-GWAS Initiative [1U19-CA148537, 1U19-CA148065, 1U19-CA148112]; U.S.
Department of Defense [DAMD17-02-1-0669, W81XWH-07-0449,
DAMD17-02-1-0666, W81XWH-10-1-0280, W81XWH-10-1-0341]; Canadian
Institutes of Health Research (CIHR) [MOP-86727, MSH-87734]; CIHR Team
in Familial Risks of Breast Cancer; Komen Foundation for the Cure;
Breast Cancer Research Foundation; Ovarian Cancer Research Fund; U.S.
Army Medical Research and Materiel Command [DAMD17-02-1-0669,
DAMD17-01-1-0729]; National Health and Medical Research Council of
Australia [199600, 400281, 209057, 251533, 396414, 504715, 1073898];
Cancer Australia [191, 211, 182]; Cancer Council Queensland; Cancer
Council Victoria; Cancer Council New South Wales; Cancer Council South
Australia; Cancer Council Tasmania; Cancer Foundation of Western
Australia; ELAN Program of the University of Erlangen-Nuremberg;
Nationaal Kankerplan of Belgium; German Federal Ministry of Education
and Research of Germany Programme of Clinical Biomedical Research [01GB
9401]; German Cancer Research Center; Roswell Park Cancer Institute
Alliance Foundation [P30 CA016056]; Rudolf-Bartling Foundation; Helsinki
University Central Hospital Research Fund; National Institutes of
Health/National Center for Research Resources/General Clinical Research
Center [M01-RR000056]; American Cancer Society Early Detection
Professorship [SIOP-06-258-01-COUN]; National Center for Advancing
Translational Sciences (NCATS) [UL1TR000124]; Danish Cancer Society
[94-222-52]; Mermaid I project; Mayo Foundation; Minnesota Ovarian
Cancer Alliance; Fred C. and Katherine B. Andersen Foundation; Cancer
Institute of New Jersey; Helse Vest; Norwegian Cancer Society; Research
Council of Norway; Radboud University Medical Centre; Oregon Health and
Science University (OHSU) Foundation; Pomeranian Medical University; UK
National Institute for Health Research Biomedical Research Centres at
the University of Cambridge; University College London Hospital; Royal
Marsden Hospital; Imperial Experimental Cancer Research Centre
[C1312/A15589]; U.S. Public Health Service [PSA-042205]; Lon V. Smith
Foundation [LVS-39420]; Eve Appeal; Oak Foundation; California Cancer
Research Program [00-01389V-20170, 2II0200]; Polish Ministry of Science
and Higher Education [4 PO5C 028 14, 2 PO5A 068 27]; Maria
Sklodowska-Curie Memorial Cancer Center; Institute of Oncology, Warsaw
FX This work was supported by: the National Cancer Institute at the U.S.
National Institutes of Health [K07-CA095666, K07-CA80668, K07-CA143047,
K22-CA138563, N01-CN025403, N01-CN55424, N01-PC67001, N01-PC67010,
P01-CA17054, P30-CA072720, P30-CA008748, P30-CA14089, P30-CA15083,
P50-CA105009, P50-CA136393, P50-CA159981, R01-CA058860, R01 CA063678,
R01 CA063682, R01-CA092044, R01-CA095023, R01-CA16056, R01-CA54419,
R01-CA58598, R01-CA61107, R01-CA61132, R01-CA76016, R01-CA83918,
R01-CA87538, R01-CA112523, R01-CA122443, R03-CA113148, R03-CA115195,
U01-CA69417, U01-CA71966 and Intramural Research funds]; the European
Commission's Seventh Framework Programme [agreement number 223175 HEALTH
F2 2009-223175]; Cancer Research UK [C490/A16561, C536/A13086,
C536/A6689, C1287/A10118, C1287/A 10710, C12292/A11174, C1281/A12014,
C5047/A8384, C5047/A15007, C5047/A10692, and C8197/A16565]; a National
Institutes of Health (CA128978), Cancer Post-GWAS Initiative
[1U19-CA148537, 1U19-CA148065 and 1U19-CA148112 - the Genetic
Associations and Mechanisms in Oncology (GAME-ON) initiative]; the U.S.
Department of Defense [DAMD17-02-1-0669, W81XWH-07-0449,
DAMD17-02-1-0666, W81XWH-10-1-0280 and W81XWH-10-1-0341]; the Canadian
Institutes of Health Research (CIHR) [MOP-86727 and MSH-87734 to L.E.K.]
and the CIHR Team in Familial Risks of Breast Cancer; the Komen
Foundation for the Cure; the Breast Cancer Research Foundation; the
Ovarian Cancer Research Fund (thanks to donations by the family and
friends of Kathryn Sladek Smith); the U.S. Army Medical Research and
Materiel Command [DAMD17-01-1-0729 and DAMD17-02-1-0669]; the National
Health and Medical Research Council of Australia [199600, 400281,
209057, 251533, 396414, 504715, 1073898 and fellowships to G.C-T. and
P.M.W.]; Cancer Australia [Multi-State Grant Application Numbers 191,
211 and 182]; Cancer Council Queensland; Cancer Council Victoria; Cancer
Council New South Wales; Cancer Council South Australia; Cancer Council
Tasmania; Cancer Foundation of Western Australia; the ELAN Program of
the University of Erlangen-Nuremberg; the Nationaal Kankerplan of
Belgium; the German Federal Ministry of Education and Research of
Germany Programme of Clinical Biomedical Research [01GB 9401]; the
German Cancer Research Center; the Roswell Park Cancer Institute
Alliance Foundation [P30 CA016056]; the Rudolf-Bartling Foundation; the
Helsinki University Central Hospital Research Fund; the National
Institutes of Health/National Center for Research Resources/General
Clinical Research Center [M01-RR000056]; an American Cancer Society
Early Detection Professorship [SIOP-06-258-01-COUN to B.Y.K.]; the
National Center for Advancing Translational Sciences (NCATS)
[UL1TR000124 to B.Y.K.]; the Danish Cancer Society [94-222-52]; the
Mermaid I project; the Mayo Foundation; the Minnesota Ovarian Cancer
Alliance; the Fred C. and Katherine B. Andersen Foundation; the Cancer
Institute of New Jersey; Helse Vest; the Norwegian Cancer Society; the
Research Council of Norway; Radboud University Medical Centre; the
Oregon Health and Science University (OHSU) Foundation; Pomeranian
Medical University; the UK National Institute for Health Research
Biomedical Research Centres at the University of Cambridge, University
College London Hospital and the Royal Marsden Hospital; the Imperial
Experimental Cancer Research Centre [C1312/A15589]; the U.S. Public
Health Service [PSA-042205]; the Lon V.; Smith Foundation [LVS-39420];
the Eve Appeal; the Oak Foundation; the California Cancer Research
Program [00-01389V-20170 and 2II0200]; the Polish Ministry of Science
and Higher Education [4 PO5C 028 14 and 2 PO5A 068 27]; and the Maria
Sklodowska-Curie Memorial Cancer Center and Institute of Oncology,
Warsaw. The funders had no role in study design, data collection and
analysis, decision to publish or preparation of the manuscript.
NR 29
TC 3
Z9 3
U1 1
U2 1
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0300-5771
EI 1464-3685
J9 INT J EPIDEMIOL
JI Int. J. Epidemiol.
PD JUN
PY 2016
VL 45
IS 3
BP 884
EP 895
DI 10.1093/ije/dyw158
PG 12
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA DX8QG
UT WOS:000384653200041
PM 27401727
ER
PT J
AU Jung, SY
Wang, M
Anderson, K
Baglietto, L
Bergkvist, L
Bernstein, L
van den Brandt, PA
Brinton, L
Buring, JE
Eliassen, AH
Falk, R
Gapstur, SM
Giles, GG
Goodman, G
Hoffman-Bolton, J
Horn-Ross, PL
Inoue, M
Kolonel, LN
Krogh, V
Lof, M
Maas, P
Miller, AB
Neuhouser, ML
Park, Y
Robien, K
Rohan, TE
Scarmo, S
Schouten, LJ
Sieri, S
Stevens, VL
Tsugane, S
Visvanathan, K
Wilkens, LR
Wolk, A
Weiderpass, E
Willett, WC
Zeleniuch-Jacquotte, A
Zhang, SM
Zhang, XH
Ziegler, RG
Smith-Warner, SA
AF Jung, Seungyoun
Wang, Molin
Anderson, Kristin
Baglietto, Laura
Bergkvist, Leif
Bernstein, Leslie
van den Brandt, Piet A.
Brinton, Louise
Buring, Julie E.
Eliassen, A. Heather
Falk, Roni
Gapstur, Susan M.
Giles, Graham G.
Goodman, Gary
Hoffman-Bolton, Judith
Horn-Ross, Pamela L.
Inoue, Manami
Kolonel, Laurence N.
Krogh, Vittorio
Lof, Marie
Maas, Paige
Miller, Anthony B.
Neuhouser, Marian L.
Park, Yikyung
Robien, Kim
Rohan, Thomas E.
Scarmo, Stephanie
Schouten, Leo J.
Sieri, Sabina
Stevens, Victoria L.
Tsugane, Schoichiro
Visvanathan, Kala
Wilkens, Lynne R.
Wolk, Alicja
Weiderpass, Elisabete
Willett, Walter C.
Zeleniuch-Jacquotte, Anne
Zhang, Shumin M.
Zhang, Xuehong
Ziegler, Regina G.
Smith-Warner, Stephanie A.
TI Alcohol consumption and breast cancer risk by estrogen receptor status:
in a pooled analysis of 20 studies
SO INTERNATIONAL JOURNAL OF EPIDEMIOLOGY
LA English
DT Article
DE Alcohol; folate; breast cancer; estrogen receptor; progesterone
receptor; pooled analyses; epidemiology; cohort study
ID DIETARY-FOLATE INTAKE; BASE-LINE CHARACTERISTICS; ONE-CARBON METABOLISM;
II NUTRITION COHORT; POSTMENOPAUSAL WOMEN; VITAMIN-C; PROPENSITY SCORE;
PLASMA FOLATE; HEALTH; METAANALYSIS
AB Background: Breast cancer aetiology may differ by estrogen receptor (ER) status. Associations of alcohol and folate intakes with risk of breast cancer defined by ER status were examined in pooled analyses of the primary data from 20 cohorts.
Methods: During a maximum of 6-18 years of follow-up of 1 089 273 women, 21 624 ER+ and 5113 ER- breast cancers were identified. Study-specific multivariable relative risks (RRs) were calculated using Cox proportional hazards regression models and then combined using a random-effects model.
Results: Alcohol consumption was positively associated with risk of ER+ and ER- breast cancer. The pooled multivariable RRs (95% confidence intervals) comparing >= 30 g/d with 0 g/day of alcohol consumption were 1.35 (1.23-1.48) for ER+ and 1.28 (1.10-1.49) for ER+ breast cancer (P-trend <= 0.001; Pcommon-effects by ER status: 0.57). Associations were similar for alcohol intake from beer, wine and liquor. The associations with alcohol intake did not vary significantly by total (from foods and supplements) folate intake (P-interaction >= 0.26). Dietary (from foods only) and total folate intakes were not associated with risk of overall, ER+ and ER- breast cancer; pooled multivariable RRs ranged from 0.98 to 1.02 comparing extreme quintiles. Following-up US studies through only the period before mandatory folic acid fortification did not change the results. The alcohol and folate associations did not vary by tumour subtypes defined by progesterone receptor status.
Conclusions: Alcohol consumption was positively associated with risk of both ER+ and ER- breast cancer, even among women with high folate intake. Folate intake was not associated with breast cancer risk.
C1 [Jung, Seungyoun; Willett, Walter C.; Smith-Warner, Stephanie A.] Harvard TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA USA.
[Jung, Seungyoun; Wang, Molin; Buring, Julie E.; Eliassen, A. Heather; Willett, Walter C.; Smith-Warner, Stephanie A.] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.
[Jung, Seungyoun] Univ Maryland, Sch Med, Dept Epidemiol & Publ Hlth, 660 Redwood St,Howard Hall 100A, Baltimore, MD 21201 USA.
[Wang, Molin] Harvard TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Anderson, Kristin] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA.
[Anderson, Kristin] Univ Minnesota, Masonic Canc Ctr, Minneapolis, MN USA.
[Baglietto, Laura; Giles, Graham G.] Canc Council Victoria, Canc Epidemiol Ctr, Carlton, Vic, Australia.
[Baglietto, Laura; Giles, Graham G.] Univ Melbourne, Ctr Mol Environm Genet & Analyt Epidemiol, Melbourne, Vic, Australia.
[Bergkvist, Leif] Cent Hosp Vasteras, Dept Surg, Vasteras, Sweden.
[Bergkvist, Leif] Cent Hosp Vasteras, Clin Res Ctr, Vasteras, Sweden.
[Bernstein, Leslie] Beckman Res Inst, Dept Populat Sci, Div Canc Etiol, Duarte, CA USA.
[Bernstein, Leslie] City Hope Natl Med Ctr, 1500 E Duarte Rd, Duarte, CA 91010 USA.
[van den Brandt, Piet A.; Schouten, Leo J.] Maastricht Univ, GROW Sch Oncol & Dev Biol, Dept Epidemiol, Maastricht, Netherlands.
[Brinton, Louise; Falk, Roni; Maas, Paige; Ziegler, Regina G.] NCI, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Buring, Julie E.; Zhang, Shumin M.] Harvard Med Sch, Brigham & Womens Hosp, Div Prevent Med, Dept Med, Boston, MA USA.
[Eliassen, A. Heather; Willett, Walter C.; Zhang, Xuehong] Brigham & Womens Hosp, Channing Div Network Med, Dept Med, Boston, MA USA.
[Eliassen, A. Heather; Willett, Walter C.; Zhang, Xuehong] Harvard Med Sch, Boston, MA USA.
[Gapstur, Susan M.; Stevens, Victoria L.] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA.
[Goodman, Gary; Neuhouser, Marian L.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, 1124 Columbia St, Seattle, WA 98104 USA.
[Hoffman-Bolton, Judith; Visvanathan, Kala] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
[Horn-Ross, Pamela L.] Canc Prevent Inst Calif, Fremont, CA USA.
[Inoue, Manami; Tsugane, Schoichiro] Natl Canc Ctr, Epidemiol & Prevent Grp, Res Ctr Canc Prevent & Screening, Tokyo, Japan.
[Inoue, Manami] Univ Tokyo, Grad Sch Med, AXA Dept Hlth & Human Secur, Tokyo, Japan.
[Kolonel, Laurence N.; Wilkens, Lynne R.] Univ Hawaii, Ctr Canc, Program Epidemiol, Honolulu, HI 96822 USA.
[Krogh, Vittorio; Sieri, Sabina] Fdn IRCCS Ist Nazl Tumori, Epidemiol & Prevent Unit, Milan, Italy.
[Lof, Marie] Linkoping Univ, Dept Clin & Expt Med, Linkoping, Sweden.
[Miller, Anthony B.] Univ Toronto, Dalla Lana Sch Publ Hlth, Toronto, ON, Canada.
[Park, Yikyung] Washington Univ, Sch Med, Dept Surg, Div Publ Hlth Sci, St Louis, MO 63110 USA.
[Robien, Kim] George Washington Univ, Milken Inst, Sch Publ Hlth, Dept Epidemiol & Biostat, Washington, DC USA.
[Rohan, Thomas E.] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA.
[Scarmo, Stephanie; Zeleniuch-Jacquotte, Anne] NYU, Sch Med, Dept Environm Med, Div Epidemiol, New York, NY USA.
[Wolk, Alicja] Karolinska Inst, Natl Inst Environm Med, Div Nutr Epidemiol, Stockholm, Sweden.
[Weiderpass, Elisabete] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
[Weiderpass, Elisabete] Univ Tromso, Dept Community Med, Fac Hlth Sci, Tromso, Norway.
[Weiderpass, Elisabete] Canc Registry Norway, Dept Res, Oslo, Norway.
[Weiderpass, Elisabete] Folkhalsan Res Ctr, Genet Epidemiol Grp, Helsinki, Finland.
RP Jung, SY (reprint author), Univ Maryland, Sch Med, Dept Epidemiol & Publ Hlth, 660 Redwood St,Howard Hall 100A, Baltimore, MD 21201 USA.
EM sjung@epi.umaryland.edu
RI Weiderpass, Elisabete/M-4029-2016;
OI Weiderpass, Elisabete/0000-0003-2237-0128; Zeleniuch-Jacquotte,
Anne/0000-0001-9350-1303
FU National Institute of Health [CA55075]; Breast Cancer Research
Foundation
FX This work was supported by a National Institute of Health grant CA55075
and a Breast Cancer Research Foundation grant.
NR 74
TC 2
Z9 2
U1 6
U2 6
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0300-5771
EI 1464-3685
J9 INT J EPIDEMIOL
JI Int. J. Epidemiol.
PD JUN
PY 2016
VL 45
IS 3
BP 916
EP 928
DI 10.1093/ije/dyv156
PG 13
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA DX8QG
UT WOS:000384653200044
PM 26320033
ER
PT J
AU Guertin, KA
Freedman, ND
Loftfield, E
Graubard, BI
Caporaso, NE
Sinha, R
AF Guertin, Kristin A.
Freedman, Neal D.
Loftfield, Erikka
Graubard, Barry I.
Caporaso, Neil E.
Sinha, Rashmi
TI Coffee consumption and incidence of lung cancer in the NIH-AARP Diet and
Health Study
SO INTERNATIONAL JOURNAL OF EPIDEMIOLOGY
LA English
DT Article
DE Coffee; caffeine; lung cancer; smoking; tobacco
ID HISTOLOGICAL TYPES; PROSPECTIVE COHORT; CIGARETTE-SMOKING;
NEVER-SMOKERS; RISK-FACTORS; MORTALITY; TEA; DRINKING; METAANALYSIS;
ASSOCIATION
AB Background: Coffee drinkers had a higher risk of lung cancer in some previous studies, but as heavy coffee drinkers tend to also be cigarette smokers, such findings could be confounded. Therefore, we examined this association in the nearly half a million participants of the US NIH-AARP Diet and Health Study.
Methods: Typical coffee intake and smoking history were queried at baseline. During 4 155 256 person-years of follow-up, more than 9000 incident lung cancer cases occurred. We used Cox proportional hazards regression to estimate hazard ratios (HRs) and 95% confidence intervals for coffee intake and subsequent incidence of lung cancer. We also comprehensively adjusted for tobacco smoking and examined associations by detailed strata of tobacco use.
Results: Coffee drinkers were far more likely to smoke than non-drinkers. Although coffee drinking was associated with lung cancer in age-and sex-adjusted models (HR for >= 6 cups/day compared with none: 4.56, 4.08-5.10), this association was substantially attenuated after adjusting for smoking (HR: 1.27, 1.14-1.42). Similar findings were observed for each different histological type of lung cancer, and for participants drinking predominantly caffeinated or decaffeinated coffee. Little evidence for an association was observed in our stratified analyses, either within never smokers or in most categories of tobacco use.
Conclusions: Coffee drinking was positively associated with lung cancer in our study, although the association was substantially attenuated after adjustment for tobacco smoking. As our adjustment for lifetime tobacco use was imperfect, it is likely that the remaining association is due to residual confounding by smoking, although other explanations are possible.
C1 [Guertin, Kristin A.; Freedman, Neal D.; Loftfield, Erikka; Sinha, Rashmi] NCI, Nutr Epidemiol Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Graubard, Barry I.] NCI, Biostat Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Caporaso, Neil E.] NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
RP Guertin, KA (reprint author), NCI, NIH, 9609 Med Ctr Dr RM 6E326,MSC 9760, Bethesda, MD 20892 USA.
EM kristin.guertin@nih.gov
FU Intramural Research Program of the National Institutes of Health,
Division of Cancer Epidemiology and Genetics, National Cancer Institute,
National Institutes of Health, Department of Health and Human Services
FX This work was supported by the Intramural Research Program of the
National Institutes of Health, Division of Cancer Epidemiology and
Genetics, National Cancer Institute, National Institutes of Health,
Department of Health and Human Services.
NR 50
TC 5
Z9 5
U1 3
U2 3
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0300-5771
EI 1464-3685
J9 INT J EPIDEMIOL
JI Int. J. Epidemiol.
PD JUN
PY 2016
VL 45
IS 3
BP 929
EP 939
DI 10.1093/ije/dyv104
PG 11
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA DX8QG
UT WOS:000384653200045
PM 26082405
ER
PT J
AU Major, EO
Nath, A
AF Major, Eugene O.
Nath, Avindra
TI A link between long-term natalizumab dosing in MS and PML Putting the
puzzle together
SO NEUROLOGY-NEUROIMMUNOLOGY & NEUROINFLAMMATION
LA English
DT Editorial Material
ID PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY; JC VIRUS
C1 [Major, Eugene O.; Nath, Avindra] NINDS, Div Neuroimmunol & Neurovirol, Intramural Res Program, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
RP Major, EO (reprint author), NINDS, Div Neuroimmunol & Neurovirol, Intramural Res Program, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
EM majorg@ninds.nih.gov
NR 10
TC 4
Z9 4
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 2332-7812
J9 NEUROL-NEUROIMMUNOL
JI Neurol.-Neuroimmunol. Neuroinflammation
PD JUN
PY 2016
VL 3
IS 3
AR e235
DI 10.1212/NXI.0000000000000235
PG 3
WC Neurosciences
SC Neurosciences & Neurology
GA DX7OO
UT WOS:000384577900017
PM 27213175
ER
PT J
AU Sylvetsky, AC
Blau, JE
Rother, KI
AF Sylvetsky, Allison C.
Blau, Jenny E.
Rother, Kristina I.
TI Understanding the metabolic and health effects of low-calorie
sweeteners: methodological considerations and implications for future
research
SO REVIEWS IN ENDOCRINE & METABOLIC DISORDERS
LA English
DT Article
DE Diet soda; Artificial sweeteners; Low-calorie sweeteners; Obesity;
Weight; Beverages; Metabolism; Study design
ID RANDOMIZED CLINICAL-TRIAL; DIET SODA INTAKE; FOOD-INTAKE; ARTIFICIAL
SWEETENERS; BODY-WEIGHT; GLUCOSE-HOMEOSTASIS; NONNUTRITIVE SWEETENERS;
OVERWEIGHT SUBJECTS; DIABETES-MELLITUS; BEVERAGE INTAKE
AB Consumption of foods, beverages, and packets containing low-calorie sweeteners (LCS) has increased markedly across gender, age, race/ethnicity, weight status, and socio-economic subgroups. However, well-controlled intervention studies rigorously evaluating the health effects of LCS in humans are limited. One of the key questions is whether LCS are indeed a beneficial strategy for weight management and prevention of obesity. The current review discusses several methodological considerations in the design and interpretation of these studies. Specifically, we focus on the selection of study participants, inclusion of an appropriate control, importance of considering habitual LCS exposure, selection of specific LCS, dose and route of LCS administration, choice of study outcomes, and the context and generalizability of the study findings. These critical considerations will guide the design of future studies and thus assist in understanding the health effects of LCS.
C1 [Sylvetsky, Allison C.] George Washington Univ, Dept Exercise & Nutr Sci, 950 New Hampshire Ave NW, Washington, DC 20052 USA.
[Sylvetsky, Allison C.; Blau, Jenny E.; Rother, Kristina I.] NIDDK, Sect Pediat Diabet & Metab, NIH, 9000 Rockville Pike,Bldg 10,Room 8C432A, Bethesda, MD 20892 USA.
RP Rother, KI (reprint author), NIDDK, Sect Pediat Diabet & Metab, NIH, 9000 Rockville Pike,Bldg 10,Room 8C432A, Bethesda, MD 20892 USA.
EM kristina.rother@nih.gov
FU Intramural Research Program of the National Institute of Diabetes and
Digestive and Kidney Diseases at the National Institutes of Health
FX This work was funded in part by the Intramural Research Program of the
National Institute of Diabetes and Digestive and Kidney Diseases at the
National Institutes of Health.
NR 72
TC 1
Z9 1
U1 18
U2 18
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 1389-9155
EI 1573-2606
J9 REV ENDOCR METAB DIS
JI Rev. Endocr. Metab. Disord.
PD JUN
PY 2016
VL 17
IS 2
BP 187
EP 194
DI 10.1007/s11154-016-9344-5
PG 8
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA DX7KJ
UT WOS:000384565500007
PM 26936185
ER
PT J
AU Hoffman, HJ
Rawal, S
Li, CM
Duffy, VB
AF Hoffman, Howard J.
Rawal, Shristi
Li, Chuan-Ming
Duffy, Valerie B.
TI New chemosensory component in the US National Health and Nutrition
Examination Survey (NHANES): first-year results for measured olfactory
dysfunction
SO REVIEWS IN ENDOCRINE & METABOLIC DISORDERS
LA English
DT Article
DE Olfaction disorders; Epidemiology; Taste; Risk factors; Public health
surveillance; Health status
ID SMELL IDENTIFICATION TEST; TEST-RETEST RELIABILITY; SELF-REPORTED SMELL;
QUALITY-OF-LIFE; ODOR IDENTIFICATION; OLDER-ADULTS; BITTER TASTE;
GENERAL-POPULATION; UNITED-STATES; OTITIS-MEDIA
AB The U.S. NHANES included chemosensory assessments in the 2011-2014 protocol. We provide an overview of this protocol and 2012 olfactory exam findings. Of the 1818 NHANES participants aged aeyen40 years, 1281 (70.5 %) completed the exam; non-participation mostly was due to time constraints. Health technicians administered an 8-item, forced-choice, odor identification task scored as normosmic (6-8 odors identified correctly) versus olfactory dysfunction, including hyposmic (4-5 correct) and anosmic/severe hyposmic (0-3 correct). Interviewers recorded self-reported smell alterations (during past year, since age 25, phantosmia), histories of sinonasal problems, xerostomia, dental extractions, head or facial trauma, and chemosensory-related treatment and changes in quality of life. Olfactory dysfunction was found in 12.4 % (13.3 million adults; 55 % males/45 % females) including 3.2 % anosmic/severe hyposmic (3.4 million; 74 % males/26 % females). Selected age-specific prevalences were 4.2 % (40-49 years), 12.7 % (60-69 years), and 39.4 % (80+ years). Among adults aeyen70 years, misidentification rates for warning odors were 20.3 % for smoke and 31.3 % for natural gas. The highest sensitivity (correctly identifying dysfunction) and specificity (correctly identifying normosmia) of self-reported olfactory alteration was among anosmics/severe hyposmics (54.4 % and 78.1 %, respectively). In age- and sex-adjusted logistic regression analysis, risk factors of olfactory dysfunction were racial/ethnic minority, income-to-poverty ratio aecurrency sign 1.1, education < high school, and heavy drinking. Moderate-to-vigorous physical activity reduced risk of impairment. Olfactory dysfunction is prevalent, particularly among older adults. Inexpensive, brief odor identification tests coupled with questions (smell problems past year, since age 25, phantosmia) could screen for marked dysfunction. Healthcare providers should be prepared to offer education on non-olfactory avoidance of hazardous events.
C1 [Hoffman, Howard J.; Li, Chuan-Ming] NIDCD, Epidemiol & Stat Program, Div Sci Programs, NIH, Bethesda, MD USA.
[Rawal, Shristi] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Intramural Populat Hlth Res, NIH, Rockville, MD USA.
[Rawal, Shristi; Duffy, Valerie B.] Univ Connecticut, Dept Allied Hlth Sci, 358 Mansfield Rd,Unit 1101, Storrs, CT 06269 USA.
RP Duffy, VB (reprint author), Univ Connecticut, Dept Allied Hlth Sci, 358 Mansfield Rd,Unit 1101, Storrs, CT 06269 USA.
EM valerie.duffy@uconn.edu
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development
FX The authors wish to thank the study participants and the dedicated staff
who helped organize and conduct the chemosensory (taste and smell)
interview and examination components in the National Health and
Nutrition Examination Survey (NHANES). We also wish to acknowledge the
valuable contribution of our colleagues, Dr. Richard Doty (University of
Pennsylvania), Dr. John Hayes (Pennsylvania State University), and Dr.
Charles Dillon (Project Officer for the 2011-2014 NHANES Chemosensory
Protocol, NCHS/CDC), as well as several experts in chemosensation
science who provided critical counsel and encouragement over sustained
periods, Dr. Linda Bartoshuk, Dr. Susan Coldwell, Dr. Beverly Cowart,
Dr. Karen Cruickshanks, Dr. Pamela Dalton, Dr. Barry Davis [deceased],
Dr. Claire Murphy, and multiple others. Also, Dr. Shristi Rawal was
partially supported by the intramural research program of the Eunice
Kennedy Shriver National Institute of Child Health and Human
Development.
NR 101
TC 2
Z9 2
U1 4
U2 4
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 1389-9155
EI 1573-2606
J9 REV ENDOCR METAB DIS
JI Rev. Endocr. Metab. Disord.
PD JUN
PY 2016
VL 17
IS 2
BP 221
EP 240
DI 10.1007/s11154-016-9364-1
PG 20
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA DX7KJ
UT WOS:000384565500010
PM 27287364
ER
PT J
AU Sousa, ADA
Johnson, KR
Nicholas, R
Darko, S
Price, DA
Douek, DC
Jacobson, S
Muraro, PA
AF Alves Sousa, Alessandra de Paula
Johnson, Kory R.
Nicholas, Richard
Darko, Sam
Price, David A.
Douek, Daniel C.
Jacobson, Steven
Muraro, Paolo A.
TI Intrathecal T-cell clonal expansions in patients with multiple sclerosis
SO ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY
LA English
DT Article
ID CEREBROSPINAL-FLUID; NERVOUS-SYSTEM; REPERTOIRE; LYMPHOCYTES; DIVERSITY;
LESIONS
AB Objective: Analysis of the T-cell receptor (TCR) repertoire in the cerebrospinal fluid (CSF) of patients with multiple sclerosis (MS) can reveal antigen-specific immune responses potentially implicated in the disease process. We applied a new unbiased deep-sequencing method for TCR repertoire analysis to accurately measure and compare receptor diversity and clonal expansions within the peripheral and CSF-trafficking T-cell populations of patients with MS and control individuals with idiopathic intracranial hypertension (IIH). Methods: Paired blood and CSF TCR beta-chain libraries from five MS patients and five IIH controls were sequenced, yielding a total of 80 million reads. Results: Although TCR repertoire diversity was greater in the blood and CSF compartments of MS patients when compared with IIH controls, it is notable that the frequency of clonal expansions was also significantly higher in both compartments of MS patients. Highly expanded T-cell clones were enriched in the CSF compartment of MS patients compared to peripheral blood, very few of them were detected in both compartments. Interpretation: Collectively, our data provide a proof of principle that private compartmentalized T-cell expansion exists in the intrathecal space of MS patients.
C1 [Alves Sousa, Alessandra de Paula; Jacobson, Steven] NINDS, Neuroimmunol Branch, Viral Immunol Sect, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
[Alves Sousa, Alessandra de Paula; Muraro, Paolo A.] Imperial Coll London, Div Brain Sci, Fac Med, London, England.
[Johnson, Kory R.] NINDS, Bioinformat Sect, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
[Nicholas, Richard] Imperial Coll Healthcare NHS Trust, London, England.
[Darko, Sam; Price, David A.; Douek, Daniel C.] NINDS, Human Immunol Sect, Vaccine Res Ctr, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
[Price, David A.] Cardiff Univ, Sch Med, Inst Infect & Immun, Cardiff, S Glam, Wales.
RP Muraro, PA (reprint author), Imperial Coll London, Wolfson Neurosci Labs, Burlington Danes Bldg,160 Du Cane Rd, London W12 0NN, England.; Jacobson, S (reprint author), NINDS, Neuroimmunol Branch, Viral Immunol Sect, Clin Res Ctr, 9000 Rockville Pike,Room 5C100, Bethesda, MD 20892 USA.
EM jacobsons@ninds.nih.gov; p.muraro@imperial.ac.uk
RI Price, David/C-7876-2013
OI Price, David/0000-0001-9416-2737
NR 23
TC 1
Z9 1
U1 3
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 2328-9503
J9 ANN CLIN TRANSL NEUR
JI Ann. Clin. Transl. Neurol.
PD JUN
PY 2016
VL 3
IS 6
BP 422
EP 433
DI 10.1002/acn3.310
PG 12
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA DX1JE
UT WOS:000384122200002
ER
PT J
AU Azoury, SC
Gilmore, RC
Shukla, V
AF Azoury, Said C.
Gilmore, Richard C.
Shukla, Vivek
TI Molecularly Targeted Agents and Immunotherapy for the Treatment of Head
and Neck Squamous Cell Cancer (HNSCC)
SO DISCOVERY MEDICINE
LA English
DT Article
ID PHASE-II-TRIAL; GROWTH-FACTOR RECEPTOR; PHOSPHATIDYLINOSITOL 3-KINASE
INHIBITOR; CHEMOTHERAPY PLUS CETUXIMAB; COLONY-STIMULATING FACTOR;
AND/OR METASTATIC HEAD; PLATINUM-BASED THERAPY; 1ST-LINE TREATMENT;
OPEN-LABEL; ADVANCED MELANOMA
AB Squamous cell carcinoma is one of the most frequent tumors of the head and neck and often presents at an advanced-stage. Traditionally, treatment for head and neck squamous cell carcinoma (HNSCC) has included surgery, radiation, and chemotherapy depending on both the site and stage of disease. Although the treatment approach for local disease is often standardized, the management of recurrent and advanced disease is evolving. A better understanding of the molecular mechanisms of HNSCC has led to numerous promising investigations and the push for the development of novel therapies. Similarly, over the past several decades, growing data supports the notion that an individual's immune system can be manipulated in such a way to help eradicate cancer. The success of immunotherapeutic agents such as interleukin therapy and immune checkpoint inhibitor blockade in cancer, particularly advanced-stage melanoma, has stimulated researchers to uncover similar success stories in HNSCC. Examples of immunotherapeutics that are being studied for the treatment of HNSCC include adoptive T-cell therapy, vaccines, and immune checkpoint inhibitor proteins (e.g., anti-CTLA-4, -PD-1, -PD-L1). Molecularly targeted agents of interest include inhibitors of transmembrane growth factor receptors, angiogenesis, and PI3K/AKT/mTOR and NOTCH signaling pathways. To date, cetuximab, an epidermal growth factor receptor inhibitor, is the only targeted agent for HNSCC that was approved by the Federal Food and Drug Administration (FDA) on the basis that it improves overall survival when combined with chemotherapy or radiation. Herein, the authors provide an up-to-date review of immunotherapeutic and molecularly targeted agents for the treatment of HNSCC.
C1 [Azoury, Said C.; Gilmore, Richard C.] Johns Hopkins Univ, Sch Med, Dept Surg, Baltimore, MD 21202 USA.
[Shukla, Vivek] NCI, Thorac & Gastrointestinal Oncol Branch, NIH, Bethesda, MD 20892 USA.
RP Shukla, V (reprint author), NCI, Thorac & Gastrointestinal Oncol Branch, NIH, Bethesda, MD 20892 USA.
EM vivek.shukla@nih.gov
NR 78
TC 1
Z9 1
U1 5
U2 5
PU DISCOVERY MEDICINE
PI TIMONIUM
PA 10 GERARD AVE, STE 201, TIMONIUM, MD 21093 USA
SN 1539-6509
EI 1944-7930
J9 DISCOV MED
JI Discov. Med.
PD JUN
PY 2016
VL 21
IS 118
BP 507
EP 516
PG 10
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA DX2KC
UT WOS:000384196800008
PM 27448787
ER
PT J
AU Gardner, EL
Bi, GH
Thakur, G
Makriyannis, A
Seltzman, HH
He, XH
Xi, ZX
AF Gardner, Eliot L.
Bi, Guo-Hua
Thakur, Ganesh
Makriyannis, Alexandros
Seltzman, Herbert H.
He, Xiang-Hu
Xi, Zheng-Xiong
TI Preclinical Evaluation of Neutral Cannabinoid CB1 Receptor Antagonists
and Cannabinoid CB1 Receptor Negative Allosteric Modulators for Treating
Drug Addiction
SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY
LA English
DT Meeting Abstract
CT 30th Seoul World Congress of the
International-College-of-Neuropsychopharmacology (CINP)
CY JUL 03-07, 2016
CL Seoul, SOUTH KOREA
SP Int Coll Neuropsychopharmacol
C1 [Gardner, Eliot L.; Bi, Guo-Hua; He, Xiang-Hu; Xi, Zheng-Xiong] NIDA, Baltimore, MD USA.
[Thakur, Ganesh; Makriyannis, Alexandros] Northeastern Univ, Boston, MA 02115 USA.
[Seltzman, Herbert H.] Res Triangle Inst, POB 12194, Res Triangle Pk, NC 27709 USA.
[He, Xiang-Hu] Wuhan Univ, Zhongnan Hosp, Wuhan, Hubei, Peoples R China.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1461-1457
EI 1469-5111
J9 INT J NEUROPSYCHOPH
JI Int. J. Neuropsychopharmacol.
PD JUN
PY 2016
VL 19
SU 1
MA PM288
BP 152
EP 152
PG 1
WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA DW8PI
UT WOS:000383917600404
ER
PT J
AU Smith, AH
Bolcho, U
Phokaew, C
Ovesen, PL
Yeo, S
Jensen, KP
Diazgranados, N
Zhao, H
Farrer, LA
Goldman, D
Glerup, S
Kranzler, HR
Nykjoer, A
Gelernter, J
AF Smith, Andrew H.
Bolcho, Ulrik
Phokaew, Chureerat
Ovesen, Peter L.
Yeo, Seungeun
Jensen, Kevin P.
Diazgranados, Nancy
Zhao, Hongyu
Farrer, Lindsay A.
Goldman, David
Glerup, Simon
Kranzler, Henry R.
Nykjoer, Anders
Gelernter, Joel
TI SORCS2 regulates alcohol withdrawal severity and excitatory synaptic
transmission
SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY
LA English
DT Meeting Abstract
CT 30th Seoul World Congress of the
International-College-of-Neuropsychopharmacology (CINP)
CY JUL 03-07, 2016
CL Seoul, SOUTH KOREA
SP Int Coll Neuropsychopharmacol
C1 [Smith, Andrew H.] Yale Sch Med, Interdept Neurosci Program, West Haven, CT USA.
[Smith, Andrew H.] Yale Sch Med, Med Scientist Training Program, West Haven, CT USA.
[Smith, Andrew H.; Phokaew, Chureerat; Jensen, Kevin P.; Gelernter, Joel] VA CT Healthcare Ctr, Dept Psychiat, Div Human Genet, New Haven, CT USA.
[Smith, Andrew H.; Phokaew, Chureerat; Jensen, Kevin P.; Gelernter, Joel] Yale Sch Med, West Haven, CT USA.
[Bolcho, Ulrik; Ovesen, Peter L.; Glerup, Simon; Nykjoer, Anders] Aarhus Univ, Danish Res Inst Translat Neurosci DANDRITE, Lundbeck Fdn,Res Ctr MIND, Nord EMBL Partnership Mol Med,Dept Biomed, DK-8000 Aarhus C, Denmark.
[Yeo, Seungeun; Goldman, David] NIAAA, Neurogenet Lab, Bethesda, MD 20892 USA.
[Diazgranados, Nancy; Goldman, David] NIAAA, Off Clin Director, NIH, Bethesda, MD 20892 USA.
[Zhao, Hongyu] Yale Sch Publ Hlth, Dept Biostat, New Haven, CT USA.
[Farrer, Lindsay A.] Boston Univ, Sch Med, Dept Med Biomed Genet, Boston, MA 02118 USA.
[Farrer, Lindsay A.] Boston Univ, Sch Med, Dept Ophthalmol, Boston, MA 02118 USA.
[Farrer, Lindsay A.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA.
[Farrer, Lindsay A.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02118 USA.
[Kranzler, Henry R.] Univ Penn, Perelman Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA.
[Kranzler, Henry R.] Corporal Michael J Crescenz VAMC, Philadelphia, PA 19104 USA.
[Nykjoer, Anders] Mayo Clin, Dept Neurosci, Jacksonville, FL 32224 USA.
[Gelernter, Joel] Yale Univ, Yale Sch Med, Dept Genet, New Haven, CT 06510 USA.
[Gelernter, Joel] Yale Univ, Yale Sch Med, Dept Neurobiol, New Haven, CT 06510 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1461-1457
EI 1469-5111
J9 INT J NEUROPSYCHOPH
JI Int. J. Neuropsychopharmacol.
PD JUN
PY 2016
VL 19
SU 1
MA PM296
BP 154
EP 155
PG 2
WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA DW8PI
UT WOS:000383917600412
ER
EF