FN Thomson Reuters Web of Science™
VR 1.0
PT J
AU Guo, L
Liu, F
Chen, S
Yang, X
Huang, J
He, J
Jaquish, CE
Zhao, Q
Gu, CC
Hixson, JE
Gu, D
AF Guo, L.
Liu, F.
Chen, S.
Yang, X.
Huang, J.
He, J.
Jaquish, C. E.
Zhao, Q.
Gu, C. C.
Hixson, J. E.
Gu, D.
TI Common variants in the Na+-coupled bicarbonate transporter genes and
salt sensitivity of blood pressure: the GenSalt study
SO JOURNAL OF HUMAN HYPERTENSION
LA English
DT Article
ID DIETARY-SODIUM; CARDIOVASCULAR-DISEASE; METABOLIC-ACIDOSIS; BASE-LINE;
HYPERTENSION; COTRANSPORTER; SYSTEM; POLYMORPHISMS; ASSOCIATION;
POTASSIUM
AB The current study comprehensively examined the association between common variants in the Na+-coupled bicarbonate transporter (NCBT) genes and blood pressure (BP) responses to dietary sodium intervention. A 7-day low-sodium followed by a 7-day high-sodium dietary intervention was conducted among 1906 Han participants from rural areas of northern China. Nine BP measurements were obtained at baseline and each intervention using a random-zero sphygmomanometer. A mixed-effect model was used to assess the additive associations of 76 common variants in five NCBT genes, including SLC4A4, SLC4A5, SLC4A7, SLC4A8 and SLC4A10, with salt sensitivity phenotypes. The Bonferroni method was used to adjust for multiple testing. SLC4A4 marker rs4254735 was significantly associated with diastolic BP (DBP) response to low-sodium intervention (P = 5.05 x 10(-4)), with mean (95% confidence interval (CI)) response of -2.91 (-3.21, -2.61) and -0.40 (-1.84, 1.05) mmHg for genotype AA and AG, respectively. In addition, BP responses to high-sodium intervention significantly increased with the number of minor C alleles of SLC4A4 marker rs10022637. Mean systolic BP responses among those with genotypes TT, CT and CC were 4.62 (4.29, 4.99), 5.94 (5.31, 6.58) and 6.00 (3.57, 8.43) mmHg (P = 1.14 x 10(-4)); mean DBP responses were 1.72 (1.41, 2.03), 3.22 (2.52, 3.92) and 3.94 (1.88, 5.99) mmHg (P = 2.26 x 10(-5)) and mean arterial pressure responses were 2.69 (2.40, 2.97), 4.13 (3.57, 4.70) and 4.61 (2.51, 6.71) mmHg (P = 2.07 x 10(-6)), respectively. In brief, the present study indicated that common variants in the SLC4A4 gene might contribute to the variation of BP responses to dietary sodium intake in Han Chinese population.
C1 [Guo, L.; Liu, F.; Chen, S.; Yang, X.; Huang, J.; Gu, D.] Chinese Acad Med Sci, State Key Lab Cardiovasc Dis, Dept Epidemiol, Fuwai Hosp,Natl Ctr Cardiovasc Dis, Beijing, Peoples R China.
[Guo, L.; Liu, F.; Chen, S.; Yang, X.; Huang, J.; Gu, D.] Peking Union Med Coll, 167 Beilishi Rd, Beijing 100037, Peoples R China.
[He, J.; Zhao, Q.] Tulane Univ, Dept Epidemiol, Sch Publ Hlth & Trop Med, New Orleans, LA 70118 USA.
[Jaquish, C. E.] NHLBI, Div Prevent & Populat Sci, NIH, Bldg 10, Bethesda, MD 20892 USA.
[Gu, C. C.] Washington Univ, St Louis Sch Med, Div Biostat, St Louis, MO USA.
[Hixson, J. E.] Univ Texas Houston, Sch Publ Hlth, Dept Epidemiol, Houston, TX USA.
RP Gu, D (reprint author), Peking Union Med Coll, 167 Beilishi Rd, Beijing 100037, Peoples R China.; Gu, D (reprint author), Chinese Acad Med Sci, Natl Ctr Cardiovasc Dis, Fuwai Hosp, State Key Lab Cardiovasc Dis, 167 Beilishi Rd, Beijing 100037, Peoples R China.
EM gudongfeng@vip.sina.com
FU National Heart, Lung, and Blood Institute, National Institutes of
Health, Bethesda, MD, USA [U01HL072507, R01HL087263, R01HL090682];
High-Tech Research and Development Program of China (863 Plan) from the
Ministry of Science and Technology of China [2012AA02A516]
FX The Genetic Epidemiology Network of Salt Sensitivity (GenSalt) is
supported by research grants (U01HL072507, R01HL087263 and R01HL090682)
from the National Heart, Lung, and Blood Institute, National Institutes
of Health, Bethesda, MD, USA. This study is also funded by a research
grant (2012AA02A516) from the High-Tech Research and Development Program
of China (863 Plan) from the Ministry of Science and Technology of
China.
NR 33
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U1 2
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PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0950-9240
EI 1476-5527
J9 J HUM HYPERTENS
JI J. Hum. Hypertens.
PD SEP
PY 2016
VL 30
IS 9
BP 543
EP 548
DI 10.1038/jhh.2015.113
PG 6
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA DT2OA
UT WOS:000381318500005
PM 26582410
ER
PT J
AU Perera, AP
Mehta, GU
Pratt, D
Quezado, MM
Gilbert, MR
Heiss, JD
AF Perera, Andrea P.
Mehta, Gautam U.
Pratt, Drew
Quezado, Martha M.
Gilbert, Mark R.
Heiss, John D.
TI Diagnosis of a growing radiation-induced skull lesion in a patient: an
unusual scar
SO JOURNAL OF NEUROSURGERY
LA English
DT Article
DE fibroblast; lesion; skull; radiotherapy; oncology
ID INDUCED FIBROSIS; CRANIAL FASCIITIS; DIFFERENTIATION; RADIOTHERAPY
AB New lesions arising from within an area of previous irradiation often present a diagnostic dilemma, with new malignancy or metastasis of particular concern. The authors report a case of reactive fibroblast proliferation emerging from a previous radiation field and presenting as a growing lesion of the frontal and parietal skull. Following complete gross resection of the skull lesion and histopathological analysis, it was discovered that this lesion consisted of dense fibroblast proliferation with areas of osteonecrosis. This unusual reactive phenomenon offers a novel differential diagnosis for a new contrast-enhancing lesion in a region of previous radiation.
C1 [Perera, Andrea P.] Queen Mary Univ London, Barts & London SMD, London, England.
[Perera, Andrea P.; Mehta, Gautam U.; Heiss, John D.] NINDS, Surg Neurol Branch, 10 Ctr Dr,Rm 3D20,MSC 1414, Bethesda, MD 20892 USA.
[Pratt, Drew; Quezado, Martha M.] NCI, Pathol Lab, NIH, Bldg 10, Bethesda, MD 20892 USA.
[Gilbert, Mark R.] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Heiss, JD (reprint author), NINDS, NIH, Surg Neurol Branch, 10 Ctr Dr,Rm 3D20,MSC 1414, Bethesda, MD 20892 USA.
EM heissj@ninds.nih.gov
OI Heiss, John/0000-0002-3890-0165
FU Intramural Research Program at the National Institute of Neurological
Disorders; Stroke (NINDS) at the National Institutes of Health (NIH)
FX This work was supported by the Intramural Research Program at the
National Institute of Neurological Disorders and Stroke (NINDS) at the
National Institutes of Health (NIH).
NR 14
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Z9 0
U1 1
U2 1
PU AMER ASSOC NEUROLOGICAL SURGEONS
PI ROLLING MEADOWS
PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA
SN 0022-3085
EI 1933-0693
J9 J NEUROSURG
JI J. Neurosurg.
PD SEP
PY 2016
VL 125
IS 3
BP 561
EP 564
DI 10.3171/2015.7.JNS15989
PG 4
WC Clinical Neurology; Surgery
SC Neurosciences & Neurology; Surgery
GA DT8YS
UT WOS:000381782300005
PM 26684773
ER
PT J
AU Mertan, FV
Greer, MD
Shih, JH
George, AK
Kongnyuy, M
Muthigi, A
Merino, MJ
Wood, BJ
Pinto, PA
Choyke, PL
Turkbey, B
AF Mertan, Francesca V.
Greer, Matthew D.
Shih, Joanna H.
George, Arvin K.
Kongnyuy, Michael
Muthigi, Akhil
Merino, Maria J.
Wood, Bradford J.
Pinto, Peter A.
Choyke, Peter L.
Turkbey, Baris
TI Prospective Evaluation of the Prostate Imaging Reporting and Data System
Version 2 for Prostate Cancer Detection
SO JOURNAL OF UROLOGY
LA English
DT Article
DE prostate; magnetic resonance imaging; diffusion magnetic resonance
imaging
ID PI-RADS; BIOPSY; GUIDELINES; DIAGNOSIS; FUSION
AB Purpose: Prostate Imaging Reporting and Data System version 2 (PI-RADSv2) was developed to standardize the interpretation and reporting of multiparametric prostate magnetic resonance imaging and provide guidelines for biopsy of multiparametric magnetic resonance imaging findings. We prospectively evaluated the cancer detection rate at each overall PI-RADSv2 score.
Materials and Methods: This prospective study included 62 consecutive patients with 116 lesions who underwent multiparametric prostate magnetic resonance imaging at 3T with PI-RADSv2 evaluation and subsequent targeted magnetic resonance imaging/transrectal ultrasound fusion guided biopsy and concurrent 12-core systematic prostate biopsy between May and September 2015. Median patient age and prostate specific antigen values were 65.5 years( range 50.3 to 76.6) and 7.10 ng/ml( range 0.47 to 863.0), respectively. Mean lesion size was 12.7 mm overall. Lesion based cancer detection rates for all tumors and for Gleason 3+4 or greater tumors at each PI-RADSv2 score were calculated. Univariate analysis was performed to assess differences in the cancer detection rate among PI-RADSv2 scores.
Results: A total of 116 lesions in 62 patients were evaluated prospectively ( 0 PI-RADS 1, 18 PI-RADS 2, 19 PI-RADS 3, 47 PI-RADS 4, 32 PI-RADS 5), and the patients underwent magnetic resonance/transrectal ultrasound fusion guided biopsy and systematic biopsy. Histopathology revealed 55 of 116( 47.4%) cancers( 17 Gleason 3+3, 16 Gleason 3+4, 6 Gleason 4+3, 12 Gleason 4+4, 3 Gleason 4+5 and 1 Gleason 5+4). Based on targeted biopsy on a per lesion basis, the overall cancer detection rates of PI-RADS 2, 3, 4 and 5 scores for all tumors was 22.2%, 15.8%, 29.8% and 78.1%, respectively. The cancer detection rate of PI-RADS 2, 3, 4 and 5 scores for Gleason 3_4 or greater tumors was 5.6%, 0%, 21.3% and 75%, respectively. Differences in the cancer detection rate between overall PI-RADS 4 and 5 scores were significant( p < 0.001 for Gleason greater than 3+3 and Gleason 3+4 or greater cancers).
Conclusions: A PI-RADS score of 5 had the highest prospective cancer detection rate (78%). A PI-RADS score of 4 had only a 30% cancer detection rate, which is lower than expected. Surprisingly, no or few significant cancers were detected at a PI-RADS score of 3 (16%). These early prospective data suggest that current criteria result in a high false-positive rate that lowers the cancer detection rate. Therefore, stricter criteria may be needed in the future to decrease false-positives and increase the cancer detection rate for PI-RADS scores of 3, 4 and 5.
C1 [Mertan, Francesca V.; Greer, Matthew D.; Choyke, Peter L.; Turkbey, Baris] NCI, Mol Imaging Program, 10 Ctr Dr,MSC 1182,Bldg 10,Room B3B85, Bethesda, MD 20892 USA.
[George, Arvin K.; Kongnyuy, Michael; Muthigi, Akhil; Pinto, Peter A.] NCI, Urol Oncol Branch, Bethesda, MD 20892 USA.
[Merino, Maria J.] NCI, Pathol Lab, Bldg 10, Bethesda, MD 20892 USA.
[Wood, Bradford J.] NCI, Ctr Intervent Oncol, Bethesda, MD 20892 USA.
[Wood, Bradford J.] NIH, Ctr Clin, Radiol & Imaging Sci, Bethesda, MD 20892 USA.
[Shih, Joanna H.] NCI, Div Canc Treatment & Diag, Biometr Res Program, NIH, Rockville, MD USA.
RP Turkbey, B (reprint author), NCI, Mol Imaging Program, 10 Ctr Dr,MSC 1182,Bldg 10,Room B3B85, Bethesda, MD 20892 USA.
EM turkbeyi@mail.nih.gov
OI Greer, Matthew/0000-0003-4409-4398
NR 14
TC 4
Z9 4
U1 0
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 SEP
PY 2016
VL 196
IS 3
BP 690
EP 696
DI 10.1016/j.juro.2016.04.057
PG 7
WC Urology & Nephrology
SC Urology & Nephrology
GA DT1WF
UT WOS:000381272100019
PM 27101772
ER
PT J
AU Turkbey, B
Pinto, PA
AF Turkbey, Baris
Pinto, Peter A.
TI Serial Anatomical Prostate Ultrasound during Prostate Cancer Active
Surveillance
SO JOURNAL OF UROLOGY
LA English
DT Editorial Material
C1 [Turkbey, Baris; Pinto, Peter A.] NCI, NIH, Bethesda, MD 20892 USA.
RP Turkbey, B (reprint author), NCI, NIH, Bethesda, MD 20892 USA.
NR 0
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 SEP
PY 2016
VL 196
IS 3
BP 733
EP 733
PG 1
WC Urology & Nephrology
SC Urology & Nephrology
GA DT1WF
UT WOS:000381272100029
PM 27264350
ER
PT J
AU Chai, TC
Moalli, PA
Richter, HE
Lake, AG
Kim, HY
Nager, CW
Sirls, LT
Brubaker, L
Kusek, JW
AF Chai, Toby C.
Moalli, Pamela A.
Richter, Holly E.
Lake, AeuMuro G.
Kim, Hae-Young
Nager, Charles W.
Sirls, Larry T.
Brubaker, Linda
Kusek, John W.
TI Preoperative Urodynamic Parameters (Valsalva Leak Point Pressure and
Maximum Urethral Closure Pressure), Urinary Collagen and Plasma Vitamin
D Levels as Predictors of Mid Urethral Sling Surgery Outcome
SO JOURNAL OF UROLOGY
LA English
DT Article
DE urethra; suburethral sling; urodynamics; biomarkers; outcome assessment
(health care)
ID NUTRITION-EXAMINATION-SURVEY; NATIONAL-HEALTH; N-TELOPEPTIDE; WOMEN;
INCONTINENCE
AB Purpose: To determine the best predictor of the mid urethral sling outcome we calculated the AUC of ROC curves of preoperative parameters, including Valsalva leak point pressure, maximum urethral closure pressure, urinary NTx (N-telopeptide of crosslinked type I collagen) and plasma vitamin D values (D2, D3 and D2 plus D3).
Materials and Methods: This was an ancillary study of TOMUS (Trial of Mid-urethral Slings) and the ValUE (Value of Urodynamics Evaluation) trial in which subjects underwent mid urethral sling surgery for stress urinary incontinence. Valsalva leak point pressure and maximum urethral closure pressure were measured in 427 subjects, whereas NTx, vitamin D2, vitamin D3 and vitamin D2 plus D3 levels were obtained from 150, 116, 115 and 116 subjects respectively. Outcome success was defined using identical outcome (subjective and objective) variables for all subjects. ROC curves with corresponding AUC values were compared.
Results: TOMUS and ValUE subjects were significantly different in age, body mass index, UDI (Urogenital Distress Inventory) scores. TOMUS subjects had a lower surgical success rate compared to ValUE subjects (66.3% vs 76.0%, p = 0.03). The AUC values of Valsalva leak point pressure, maximum urethral closure pressure, NTx, and vitamins D2, D3 and D2 plus D3 were 0.542, 0.561, 0.702, 0.627, 0.645 and 0.640, respectively. The AUC of NTx was significantly higher than the AUCs of Valsalva leak point pressure and maximum urethral closure pressure (p = 0.02 and 0.03, respectively).
Conclusions: Urinary NTx was the best predictor of the mid urethral sling outcome. This test is not only noninvasive, it is also modifiable. Finding ideal modifiable risk factors prior to mid urethral sling surgery should be subject to future investigations.
C1 [Chai, Toby C.; Lake, AeuMuro G.] Yale Univ, Sch Med, Dept Urol, 789 Howard Ave,FMP 309,POB 208058, New Haven, CT 06520 USA.
[Chai, Toby C.; Lake, AeuMuro G.] Yale Univ, Sch Med, Dept Obstet Gynecol & Reprod Sci, New Haven, CT USA.
[Moalli, Pamela A.] Univ Pittsburgh, Dept Obstet Gynecol & Reprod Sci, Pittsburgh, PA USA.
[Richter, Holly E.] Univ Alabama Birmingham, Dept Obstet & Gynecol, Birmingham, AL 35294 USA.
[Kim, Hae-Young] New England Res Inst, 9 Galen St, Watertown, MA 02172 USA.
[Nager, Charles W.] Univ Calif San Diego, Dept Reprod Med, San Diego, CA 92103 USA.
[Sirls, Larry T.] Beaumont Hosp, Dept Urol, Royal Oak, MI USA.
[Brubaker, Linda] Loyola Univ, Chicago, IL 60611 USA.
[Kusek, John W.] NIDDK, Bethesda, MD 20892 USA.
RP Chai, TC (reprint author), Yale Univ, Sch Med, Dept Urol, 789 Howard Ave,FMP 309,POB 208058, New Haven, CT 06520 USA.
EM toby.chai@yale.edu
FU National Institutes of Health/National Institute of Diabetes and
Digestive and Kidney Diseases [U01-DK058229]
FX Supported by National Institutes of Health/National Institute of
Diabetes and Digestive and Kidney Diseases U01-DK058229.
NR 13
TC 1
Z9 1
U1 2
U2 2
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 SEP
PY 2016
VL 196
IS 3
BP 819
EP 823
DI 10.1016/j.juro.2016.03.177
PG 5
WC Urology & Nephrology
SC Urology & Nephrology
GA DT1WF
UT WOS:000381272100065
PM 27113967
ER
PT J
AU Garcia-Beltran, WF
Holzemer, A
Martrus, G
Chung, AW
Pacheco, Y
Simoneau, CR
Rucevic, M
Lamothe-Molina, PA
Pertel, T
Kim, TE
Dugan, H
Alter, G
Dechanet-Merville, J
Jost, S
Carrington, M
Altfeld, M
AF Garcia-Beltran, Wilfredo F.
Hoelzemer, Angelique
Martrus, Gloria
Chung, Amy W.
Pacheco, Yovana
Simoneau, Camille R.
Rucevic, Marijana
Lamothe-Molina, Pedro A.
Pertel, Thomas
Kim, Tae-Eun
Dugan, Haley
Alter, Galit
Dechanet-Merville, Julie
Jost, Stephanie
Carrington, Mary
Altfeld, Marcus
TI Open conformers of HLA-F are high-affinity ligands of the activating
NK-cell receptor KIR3DS1
SO NATURE IMMUNOLOGY
LA English
DT Article
ID IMMUNOGLOBULIN-LIKE RECEPTOR; NATURAL-KILLER-CELL; MHC-I MOLECULES;
CUTTING EDGE; DISEASE PROGRESSION; SURFACE EXPRESSION; PROTEIN; HIV-1;
ANTIBODIES; COMPLEX
AB The activating natural killer (NK)-cell receptor KIR3DS1 has been linked to the outcome of various human diseases, including delayed progression of disease caused by human immunodeficiency virus type 1 (HIV-1), yet a ligand that would account for its biological effects has remained unknown. We screened 100 HLA class I proteins and found that KIR3DS1 bound to HLA-F, a result we confirmed biochemically and functionally. Primary human KIR3DS1(+) NK cells degranulated and produced antiviral cytokines after encountering HLA-F and inhibited HIV-1 replication in vitro. Activation of CD4(+) T cells triggered the transcription and surface expression of HLA-F mRNA and HLA-F protein, respectively, and induced binding of KIR3DS1. HIV-1 infection further increased the transcription of HLA-F mRNA but decreased the binding of KIR3DS1, indicative of a mechanism for evading recognition by KIR3DS1(+) NK cells. Thus, we have established HLA-F as a ligand of KIR3DS1 and have demonstrated cell-context-dependent expression of HLA-F that might explain the widespread influence of KIR3DS1 in human disease.
C1 [Garcia-Beltran, Wilfredo F.; Hoelzemer, Angelique; Chung, Amy W.; Pacheco, Yovana; Simoneau, Camille R.; Rucevic, Marijana; Lamothe-Molina, Pedro A.; Kim, Tae-Eun; Dugan, Haley; Alter, Galit; Jost, Stephanie; Carrington, Mary; Altfeld, Marcus] MGH MIT & Harvard, Ragon Inst, Cambridge, MA USA.
[Hoelzemer, Angelique; Martrus, Gloria; Altfeld, Marcus] Leibniz Inst Expt Virol, Heinrich Pette Inst, Hamburg, Germany.
[Hoelzemer, Angelique] Univ Med Ctr Eppendorf, Dept Internal Med 1, Hamburg, Germany.
[Pacheco, Yovana] Univ Nuestra Senora Rosario, Fac Ciencias, Dept Maternat, Bogota, Colombia.
[Pertel, Thomas] Harvard Med Sch, Brigham & Womens Hosp, Ctr Neurol Dis, Boston, MA USA.
[Dechanet-Merville, Julie] Univ Bordeaux, CNRS, UMR 5164, Bordeaux, France.
[Carrington, Mary] Frederick Natl Lab Canc Res, Canc & Inflammat Program, Expt Immunol Lab, Leidos Biomed Res, Frederick, MD USA.
RP Altfeld, M (reprint author), MGH MIT & Harvard, Ragon Inst, Cambridge, MA USA.; Altfeld, M (reprint author), Leibniz Inst Expt Virol, Heinrich Pette Inst, Hamburg, Germany.
EM marcus.altfeld@hpi.uni-hamburg.de
FU Ragon Institute Flow Cytometry Core and Virology Core; US National
Institutes of Health [R01-AI067031-08, P01-AI104715, F31AI116366]; US
National Institutes of Health (Intramural Research Program, Frederick
National Lab, Center for Cancer Research); National Institute of General
Medical Sciences [T32GM007753]; Ragon Institute of MGH; Ragon Institute
of MIT; Ragon Institute of Harvard; Frederick National Laboratory for
Cancer Research [HHSN261200800001E]; Heinrich-Pette Institute-Leibniz
Institute for Experimental Virology (Program Area Antiviral Targets and
Strategies); German Center for Infection Research
FX We thank C. Korner and A. Crespo for advice and discussions; D. Campana
(St. Jude Children's Research Hospital) for K562 cells expressing
mbIL-15 and CD137L; C. Brander (Ragon Institute of MGH, MIT, and
Harvard) for 721.221 cells transduced to express HLA; J. Strominger
(Harvard University) for 721.221-HLA-G cells; F. Zhang (Broad Institute
of MIT and Harvard) for the lentiCas9-Blast plasmid; L. Ferreira
(Harvard University) and T. Meissner (Harvard University) for
beta2m-targeting single-guide RNA plasmid; and the Ragon
Institute Flow Cytometry Core and Virology Core for support and
assistance. Supported by the US National Institutes of Health
(R01-AI067031-08 and P01-AI104715; F31AI116366 to W.F.G.-B.; the
Intramural Research Program, Frederick National Lab, Center for Cancer
Research), the National Institute of General Medical Sciences
(T32GM007753), the Ragon Institute of MGH, MIT and Harvard, the
Frederick National Laboratory for Cancer Research (HHSN261200800001E),
the Heinrich-Pette Institute-Leibniz Institute for Experimental Virology
(Program Area Antiviral Targets and Strategies) and the German Center
for Infection Research. The content is solely the responsibility of the
authors and does not necessarily represent the official views or
policies of the National Institute of General Medical Sciences, the
National Institutes of Health, or the Department of Health and Human
Services, nor does mention of trade names, commercial products, or
organizations imply endorsement by the US Government.
NR 50
TC 6
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U1 2
U2 3
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 SEP
PY 2016
VL 17
IS 9
BP 1067
EP 1074
DI 10.1038/ni.3513
PG 8
WC Immunology
SC Immunology
GA DT9OO
UT WOS:000381832000010
PM 27455421
ER
PT J
AU Heilig, M
Epstein, DH
Nader, MA
Shaham, Y
AF Heilig, Markus
Epstein, David H.
Nader, Michael A.
Shaham, Yavin
TI Time to connect: bringing social context into addiction neuroscience
SO NATURE REVIEWS NEUROSCIENCE
LA English
DT Review
ID OPIOID-RECEPTOR GENE; CORTICOTROPIN-RELEASING-FACTOR; PLACEBO-CONTROLLED
TRIAL; RANDOMIZED CONTROLLED-TRIAL; SUBSTANCE USE DISORDERS;
ALCOHOL-DEPENDENCE; DRUG-ADDICTION; ANIMAL-MODELS; DOUBLE-BLIND;
ATTACHMENT BEHAVIOR
AB Research on the neural substrates of drug reward, withdrawal and relapse has yet to be translated into significant advances in the treatment of addiction. One potential reason is that this research has not captured a common feature of human addiction: progressive social exclusion and marginalization. We propose that research aimed at understanding the neural mechanisms that link these processes to drug seeking and drug taking would help to make addiction neuroscience research more clinically relevant.
C1 [Heilig, Markus] Linkoping Univ, Ctr Social & Affect Neurosci, Dept Clin & Expt Med IKE, SE-58183 Linkoping, Sweden.
[Epstein, David H.; Shaham, Yavin] NIDA, Intramural Res Program, NIH, Baltimore, MD 21044 USA.
[Nader, Michael A.] Wake Forest Sch Med, Dept Physiol & Pharmacol, Winston Salem, NC 27157 USA.
RP Heilig, M (reprint author), Linkoping Univ, Ctr Social & Affect Neurosci, Dept Clin & Expt Med IKE, SE-58183 Linkoping, Sweden.
EM markus.heilig@liu.se
FU Swedish Research Council; Intramural Research Program of the US National
Institutes of Health; US National Institute on Drug Abuse [DA010584,
DA017763]
FX The writing of this article was supported in part by a grant from the
Swedish Research Council (M.H.), the Intramural Research Program of the
US National Institutes of Health and the US National Institute on Drug
Abuse (D.H.E. and Y.S.) and grants DA010584 and DA017763 (M.A.N.). The
authors are grateful to S. N. Haber at the University of Rochester, New
York, USA, and her co-workers for producing and providing Figure 3. The
authors apologize to their many friends and colleagues for not citing
many reviews and empirical papers relevant to the topic of their paper,
owing to format restrictions.
NR 127
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U1 11
U2 21
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1471-003X
EI 1471-0048
J9 NAT REV NEUROSCI
JI Nat. Rev. Neurosci.
PD SEP
PY 2016
VL 17
IS 9
BP 592
EP 599
DI 10.1038/nrn.2016.67
PG 8
WC Neurosciences
SC Neurosciences & Neurology
GA DU5MK
UT WOS:000382255600012
PM 27277868
ER
PT J
AU Bandres-Ciga, S
Price, TR
Barrero, FJ
Escamilla-Sevilla, F
Pelegrina, J
Arepalli, S
Hernandez, D
Gutierrez, B
Cervilla, J
Rivera, M
Rivera, A
Ding, JH
Vives, F
Nalls, M
Singleton, A
Duran, R
AF Bandres-Ciga, Sara
Price, Timothy Ryan
Barrero, Francisco Javier
Escamilla-Sevilla, Francisco
Pelegrina, Javier
Arepalli, Sampath
Hernandez, Dena
Gutierrez, Blanca
Cervilla, Jorge
Rivera, Margarita
Rivera, Alberto
Ding, Jing-hui
Vives, Francisco
Nalls, Michael
Singleton, Andrew
Duran, Raquel
TI Genome-wide assessment of Parkinson's disease in a Southern Spanish
population
SO NEUROBIOLOGY OF AGING
LA English
DT Article
DE Parkinson's disease; Genetics; GWAS; Southern Spain
ID RISK LOCI; GENETIC RISK; MUTATIONS; ASSOCIATION; ONSET; METAANALYSIS;
AGE; IDENTIFICATION; VARIANTS; COMPLEX
AB Here, we set out to study the genetic architecture of Parkinson's disease (PD) through a Genome-Wide Association Study in a Southern Spanish population. About 240 PD cases and 192 controls were geno-typed on the NeuroX array. We estimated genetic variation associated with PD risk and age at onset (AAO). Risk profile analyses for PD and AAO were performed using a weighted genetic risk score. Total heritability was estimated by genome-wide complex trait analysis. Rare variants were screened with single-variant and burden tests. We also screened for variation in known PD genes. Finally, we explored runs of homozygosity and structural genomic variations. We replicate PD association (uncorrected p-value < 0.05) at the following loci: ACMSD/TMEM163, MAPT, STK39, MIR4697, and SREBF/RAI1. Subjects in the highest genetic risk score quintile showed significantly increased risk of PD versus the lowest quintile (odds ratio - 3.6, p-value < 4e(-7)), but no significant difference in AAO. We found evidence of runs of homozygosity in 2 PD-associated regions: one intersecting the HLA-DQB1 gene in 6 patients and 1 control; and another intersecting the GBA-SYT11 gene in PD case. The GBA N370S and the LRRK2 G2019S variants were found in 8 and 7 cases, respectively, replicating previous work. A structural variant was found in 1 case in the PARK2 gene locus. This current work represents a comprehensive assessment at a genome-wide level characterizing a novel population in PD genetics. (C) 2016 Elsevier Inc. All rights reserved.
C1 [Bandres-Ciga, Sara; Vives, Francisco; Duran, Raquel] Univ Granada, Ctr Invest Biomed CIBM, Dept Physiol, Granada 18016, Spain.
[Bandres-Ciga, Sara; Gutierrez, Blanca; Cervilla, Jorge; Rivera, Margarita; Vives, Francisco; Duran, Raquel] Univ Granada, Ctr Invest Biomed CIBM, Inst Neurosci Federico Oloriz, Granada 18016, Spain.
[Price, Timothy Ryan; Arepalli, Sampath; Hernandez, Dena; Rivera, Alberto; Ding, Jing-hui; Nalls, Michael; Singleton, Andrew] NIA, Neurogenet Lab, NIH, Bethesda, MD USA.
[Barrero, Francisco Javier; Pelegrina, Javier] Univ Hosp San Cecilio, Movement Disorders Unit, Granada, Spain.
[Escamilla-Sevilla, Francisco] Univ Hosp Virgen Nieves, Inst Invest Biosanitaria IBS, Dept Neurol, Movement Disorders Unit, Granada, Spain.
[Gutierrez, Blanca; Cervilla, Jorge; Rivera, Margarita] Univ Granada, Ctr Invest Biomed CIBM, Dept Psychiat, Granada, Spain.
[Gutierrez, Blanca; Cervilla, Jorge; Rivera, Margarita] Univ Granada, CIBER Salud Mental CIBERSAM, Granada, Spain.
RP Duran, R (reprint author), Univ Granada, Ctr Invest Biomed CIBM, Dept Physiol, Granada 18016, Spain.; Duran, R (reprint author), Univ Granada, Ctr Invest Biomed CIBM, Inst Neurosci Federico Oloriz, Granada 18016, Spain.
EM rduran@ugr.es
RI Cervilla, Jorge/O-2106-2016; DURAN , RAQUEL/D-7784-2016;
OI Cervilla, Jorge/0000-0001-6891-1992; DURAN , RAQUEL/0000-0002-5749-8968;
Bandres Ciga, Sara/0000-0003-0056-1361
FU Intramural Research Program of the National Institute on Aging, National
Institutes of Health, Department of Health and Human Services [ZO1
AG000949]; Junta de Andalucia [PI0322/2009]; Andalusian Society of
Neurology; FPU fellowship [FPU12-01885]; Spanish Ministry of Education
and Science [EST14/0061]; [CVI-6476]; [PSI2014-57643]
FX The authors are grateful to the participants in this study without whom
this work would not have been possible. Sara Bandres Ciga and Timothy
Ryan Price contributed equally to this work. Andrew Singleton, Michael
Nalls, Dena Hernandez, Raquel Duran, and Francisco Vives contributed to
study concept, design, revision, and critique. Sampath Arepalli and Sara
Bandres Ciga contributed for execution of the laboratory work. Timothy
Ryan Price, Sara Bandres Ciga, Alberto Rivera, and Jing-Hui Ding
contributed for data analysis. Francisco Barrero-Hernandez, Francisco
Escamilla-Sevilla, Javier Pelegrina, Blanca Gutierrez, Jorge Cervilla,
and Margarita Rivera contributed to neurological-clinical assessment,
patient and control recruitment, and sample collection. This work was
supported in part by the Intramural Research Program of the National
Institute on Aging, National Institutes of Health, part of the
Department of Health and Human Services (project ZO1 AG000949), the
following grants from the Junta de Andalucia; PI0322/2009 to the group
CTS-6682; CVI-6476 and PSI2014-57643 to the CTS-438 group, and a
research award from the Andalusian Society of Neurology. Sara Bandres
Ciga held an FPU fellowship FPU12-01885 and a short-term stay grant
EST14/0061 from the Spanish Ministry of Education and Science.
NR 45
TC 0
Z9 0
U1 10
U2 10
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 SEP
PY 2016
VL 45
AR 213.e3
DI 10.1016/j.neurobiolaging.2016.06.001
PG 7
WC Geriatrics & Gerontology; Neurosciences
SC Geriatrics & Gerontology; Neurosciences & Neurology
GA DS9HF
UT WOS:000381092900026
PM 27393345
ER
PT J
AU Padayatty, SJ
Levine, M
AF Padayatty, S. J.
Levine, M.
TI Vitamin C: the known and the unknown and Goldilocks
SO ORAL DISEASES
LA English
DT Review
DE vitamin C; dehydroascorbic acid; vitamin C transport; scurvy;
dose-concentration relationship; recommended dietary allowance
ID L-ASCORBIC-ACID; HYPOXIA-INDUCIBLE FACTOR; RECOMMENDED DIETARY
ALLOWANCE; CHRONIC GRANULOMATOUS-DISEASE; PAROXYSMAL-NOCTURNAL
HEMOGLOBINURIA; ENDOTHELIUM-DEPENDENT VASODILATION; PERFORMANCE
LIQUID-CHROMATOGRAPHY; HUMAN ERYTHROCYTE-MEMBRANES; ACUTE
MYOCARDIAL-INFARCTION; RANDOMIZED CONTROLLED-TRIAL
AB Vitamin C (Ascorbic Acid), the antiscorbutic vitamin, cannot be synthesized by humans and other primates, and has to be obtained from diet. Ascorbic acid is an electron donor and acts as a cofactor for fifteen mammalian enzymes. Two sodium-dependent transporters are specific for ascorbic acid, and its oxidation product dehydroascorbic acid is transported by glucose transporters. Ascorbic acid is differentially accumulated by most tissues and body fluids. Plasma and tissue vitamin C concentrations are dependent on amount consumed, bioavailability, renal excretion, and utilization. To be biologically meaningful or to be clinically relevant, in vitro and in vivo studies of vitamin C actions have to take into account physiologic concentrations of the vitamin. In this paper, we review vitamin C physiology; the many phenomena involving vitamin C where new knowledge has accrued or where understanding remains limited; raise questions about the vitamin that remain to be answered; and explore lines of investigations that are likely to be fruitful.
C1 [Padayatty, S. J.; Levine, M.] NIDDK, Mol & Clin Nutr Sect, Digest Dis Branch, NIH, Bldg 10,Room 4D52,MSC 1372, Bethesda, MD 20892 USA.
RP Padayatty, SJ (reprint author), NIDDK, Mol & Clin Nutr Sect, Digest Dis Branch, NIH, Bldg 10,Room 4D52,MSC 1372, Bethesda, MD 20892 USA.
EM sebastianp@intra.niddk.nih.gov
FU Intramural Research Program, National Institute of Diabetes and
Digestive and Kidney Diseases, National Institutes of Health
[1ZIADK053211-08]
FX This work was supported by the Intramural Research Program, National
Institute of Diabetes and Digestive and Kidney Diseases, National
Institutes of Health (Project no: 1ZIADK053211-08). SJP thanks Drs.
Michael Espey, Peter Eck, and Nermi Parrow for helpful suggestions; Dr.
Eck for information on SVCT SNPs deposited in databases; and Ethan
Tyler, NIH Medical Arts, for new and modified illustrations.
NR 331
TC 1
Z9 1
U1 23
U2 25
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1354-523X
EI 1601-0825
J9 ORAL DIS
JI Oral Dis.
PD SEP
PY 2016
VL 22
IS 6
BP 463
EP 493
DI 10.1111/odi.12446
PG 31
WC Dentistry, Oral Surgery & Medicine
SC Dentistry, Oral Surgery & Medicine
GA DS8PB
UT WOS:000381044200003
PM 26808119
ER
PT J
AU Arimbasseri, AG
Iben, J
Wei, FY
Rijal, K
Tomizawa, K
Hafner, M
Maraia, RJ
AF Arimbasseri, Aneeshkumar G.
Iben, James
Wei, Fan-Yan
Rijal, Keshab
Tomizawa, Kazuhito
Hafner, Markus
Maraia, Richard J.
TI Evolving specificity of tRNA 3-methyl-cytidine-32 (m(3)C32)
modification: a subset of tRNAs(Ser) requires N-6-isopentenylation of
A37
SO RNA
LA English
DT Article
DE anticodon loop; isopentenylation; tRNA-HySeq
ID MULTIPLE SEQUENCE ALIGNMENT; TRNA(PHE) ANTICODON LOOP; BINDING PROTEIN
ABP140; SERINE TRANSFER-RNA; SACCHAROMYCES-CEREVISIAE;
THERMUS-THERMOPHILUS; NUCLEOTIDE-SEQUENCES; HIGH-THROUGHPUT; BOVINE
LIVER; LA PROTEIN
AB Post-transcriptional modifications of anticodon loop (ACL) nucleotides impact tRNA structure, affinity for the ribosome, and decoding activity, and these activities can be fine-tuned by interactions between nucleobases on either side of the anticodon. A recently discovered ACL modification circuit involving positions 32, 34, and 37 is disrupted by a human disease-associated mutation to the gene encoding a tRNA modification enzyme. We used tRNA-HydroSeq (-HySeq) to examine (3)methyl-cytidine-32 (m(3)C32), which is found in yeast only in the ACLs of tRNAs(Ser) and tRNAs(Thr). In contrast to that reported for Saccharomyces cerevisiae in which all m(3)C32 depends on a single gene, TRM140, the m(3)C32 of tRNAs(Ser) and tRNAs(Thr) of the fission yeast S. pombe, are each dependent on one of two related genes, trm140(+) and trm141(+), homologs of which are found in higher eukaryotes. Interestingly, mammals and other vertebrates contain a third homolog and also contain m(3)C at new sites, positions 32 on tRNAs(Arg) and C47:3 in the variable arm of tRNAs(Ser). More significantly, by examining S. pombe mutants deficient for other modifications, we found that m(3)C32 on the three tRNAs(Ser) that contain anticodon base A36, requires N-6-isopentenyl modification of A37 (i(6)A37). This new C32 A37 ACL circuitry indicates that i(6)A37 is a pre- or corequisite for m(3)C32 on these tRNAs. Examination of the tRNA database suggests that such circuitry may be more expansive than observed here. The results emphasize two contemporary themes, that tRNA modifications are interconnected, and that some specific modifications on tRNAs of the same anticodon identity are species-specific.
C1 [Arimbasseri, Aneeshkumar G.; Iben, James; Rijal, Keshab] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Intramural Res Program, NIH, Bethesda, MD 20892 USA.
[Wei, Fan-Yan; Tomizawa, Kazuhito] Kumamoto Univ, Dept Mol Physiol, Fac Life Sci, Kumamoto 8600862, Japan.
[Hafner, Markus] NIAMSD, Natl Inst Hlth, Bethesda, MD 20892 USA.
[Maraia, Richard J.] US PHS, Commissioned Corps, Washington, DC 20201 USA.
[Arimbasseri, Aneeshkumar G.] North Carolina State Univ, Dept Biomol & Chem Engn, Raleigh, NC 27606 USA.
RP Maraia, RJ (reprint author), US PHS, Commissioned Corps, Washington, DC 20201 USA.
EM maraiar@mail.nih.gov
OI Arimbasseri, Gopalakrishnan Aneeshkumar/0000-0001-5266-2688
FU Intramural Research Program of the Eunice Kennedy Shriver National
Institute of Child Health and Human Development; National Institute of
Arthritis and Musculoskeletal and Skin Diseases, National Institutes of
Health
FX A.G.A. thanks S. Mattijssen for cell lines and advice with tissue
culture, and M. Blum for media preparation. This work was supported by
the Intramural Research Program of the Eunice Kennedy Shriver National
Institute of Child Health and Human Development, and National Institute
of Arthritis and Musculoskeletal and Skin Diseases, National Institutes
of Health.
NR 57
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U1 0
U2 1
PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
PI COLD SPRING HARBOR
PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA
SN 1355-8382
EI 1469-9001
J9 RNA
JI RNA
PD SEP
PY 2016
VL 22
IS 9
BP 1400
EP 1410
DI 10.1261/rna.056259.116
PG 11
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA DU1GV
UT WOS:000381957100011
PM 27354703
ER
PT J
AU Koob, GF
AF Koob, George F.
TI Corticotropin-Releasing Factor From Rodents to Primates: Translational
Hope Expresses Itself, Pun Intended
SO BIOLOGICAL PSYCHIATRY
LA English
DT Editorial Material
ID STRESS; BEHAVIORS; CRF
C1 [Koob, George F.] NIAAA, NIH, Bethesda, MD USA.
RP Koob, GF (reprint author), NIAAA, 5635 Fishers Lane,Room 2001,Suite 2000, Rockville, MD 20852 USA.
EM george.koob@nih.gov
RI koob, george/P-8791-2016
NR 10
TC 0
Z9 0
U1 1
U2 4
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 SEP 1
PY 2016
VL 80
IS 5
BP 340
EP 342
DI 10.1016/j.biopsych.2016.06.015
PG 3
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA DS5RR
UT WOS:000380840500004
PM 27499011
ER
PT J
AU Grillon, C
Ernst, M
AF Grillon, Christian
Ernst, Monique
TI Gain in Translation: Is It Time for Thigmotaxis Studies in Humans?
SO BIOLOGICAL PSYCHIATRY
LA English
DT Editorial Material
ID PROGRESS; ANXIETY; MODEL
C1 [Grillon, Christian; Ernst, Monique] NIMH, Sect Neurobiol Fear & Anxiety, NIH, Bethesda, MD 20892 USA.
RP Grillon, C (reprint author), NIMH, MAP, 15K North Dr,Bldg 15K,Room 203,MSC 2670, Bethesda, MD 20892 USA.
EM christian.grillon@nih.gov
FU Intramural NIH HHS [Z01 MH002798-07]; NIMH NIH HHS [Z01 MH002798]
NR 10
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 0006-3223
EI 1873-2402
J9 BIOL PSYCHIAT
JI Biol. Psychiatry
PD SEP 1
PY 2016
VL 80
IS 5
BP 343
EP 344
DI 10.1016/j.biopsych.2016.07.003
PG 2
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA DS5RR
UT WOS:000380840500005
PM 27499012
ER
PT J
AU Lansford, JE
Bornstein, MH
Deater-Deckard, K
Dodge, KA
Al-Hassan, SM
Bacchini, D
Bombi, AS
Chang, L
Chen, BB
Di Giunta, L
Malone, PS
Oburu, P
Pastorelli, C
Skinner, AT
Sorbring, E
Steinberg, L
Tapanya, S
Alampay, LP
Tirado, LMU
Zelli, A
AF Lansford, Jennifer E.
Bornstein, Marc H.
Deater-Deckard, Kirby
Dodge, Kenneth A.
Al-Hassan, Suha M.
Bacchini, Dario
Bombi, Anna Silvia
Chang, Lei
Chen, Bin-Bin
Di Giunta, Laura
Malone, Patrick S.
Oburu, Paul
Pastorelli, Concetta
Skinner, Ann T.
Sorbring, Emma
Steinberg, Laurence
Tapanya, Sombat
Alampay, Liane P.
Uribe Tirado, Liliana M.
Zelli, Arnaldo
TI How International Research on Parenting Advances Understanding of Child
Development
SO CHILD DEVELOPMENT PERSPECTIVES
LA English
DT Article
DE child development; culture; international research; parenting
ID 9 COUNTRIES; ACCEPTANCE-REJECTION; ADJUSTMENT; DISCIPLINE;
NORMATIVENESS; ASSOCIATIONS; AMERICAN; CULTURE; CHINESE; WARMTH
AB International research on parenting and child development can advance our understanding of similarities and differences in how parenting is related to children's development across countries. Challenges to conducting international research include operationalizing culture, disentangling effects within and between countries, and balancing emic and etic perspectives. Benefits of international research include testing whether findings regarding parenting and child development replicate across diverse samples, incorporating cultural and contextual diversity to foster more inclusive and representative research samples and investigators than has typically occurred, and understanding how children develop in proximal parenting and family and distal international contexts.
C1 [Lansford, Jennifer E.; Dodge, Kenneth A.; Malone, Patrick S.; Skinner, Ann T.] Duke Univ, Durham, NC 27706 USA.
[Bornstein, Marc H.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA.
[Deater-Deckard, Kirby] Univ Massachusetts, Amherst, MA 01003 USA.
[Al-Hassan, Suha M.] Hashemite Univ, Zarqa, Jordan.
[Al-Hassan, Suha M.] Emirates Coll Adv Educ, Abu Dhabi, U Arab Emirates.
[Bacchini, Dario] Univ Naples 2, Naples, Italy.
[Bombi, Anna Silvia; Di Giunta, Laura; Pastorelli, Concetta] Univ Roma La Sapienza, Rome, Italy.
[Chang, Lei] Univ Macau, Zhuhai, Peoples R China.
[Chen, Bin-Bin] Fudan Univ, Shanghai, Peoples R China.
[Oburu, Paul] Maseno Univ, Kisumu, Kenya.
[Sorbring, Emma] Univ West, Trollhattan, Sweden.
[Steinberg, Laurence] Temple Univ, Philadelphia, PA 19122 USA.
[Steinberg, Laurence] King Abdulaziz Univ, Jeddah, Saudi Arabia.
[Tapanya, Sombat] Chiang Mai Univ, Chiang Mai, Thailand.
[Alampay, Liane P.] Ateneo Manila Univ, Quezon City, Philippines.
[Uribe Tirado, Liliana M.] Univ San Buenaventura, Cali, Colombia.
[Zelli, Arnaldo] Univ Rome Foro Italico, Rome, Italy.
RP Lansford, JE (reprint author), Duke Univ, Ctr Child & Family Policy, Box 90545, Durham, NC 27708 USA.
EM lansford@duke.edu
OI ZELLI, Arnaldo/0000-0003-4020-8159
FU Jacobs Foundation; Eunice Kennedy Shriver National Institute of Child
Health and Human Development (NICHD) [RO1-HD054805]; Fogarty
International Center [RO3-TW008141]; National Institute on Drug Abuse
[K01DA024116, 2K05 DA015226]; Intramural Research Program of the
National Institutes of Health/NICHD
FX This article was prepared, in part, during a Marbach Residence Program
funded by the Jacobs Foundation. The research featured in this article
was funded by the Eunice Kennedy Shriver National Institute of Child
Health and Human Development (NICHD; Grant RO1-HD054805) and the Fogarty
International Center (Grant RO3-TW008141). Patrick S. Malone is
supported by Grant K01DA024116 from the National Institute on Drug
Abuse. Kenneth A. Dodge is supported by Senior Scientist award 2K05
DA015226 from the National Institute on Drug Abuse. This research also
was supported by the Intramural Research Program of the National
Institutes of Health/NICHD. The content is solely the responsibility of
the authors and does not necessarily represent the official views of the
NIH or NICHD.
NR 42
TC 0
Z9 0
U1 7
U2 10
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1750-8592
EI 1750-8606
J9 CHILD DEV PERSPECT
JI Child Develop. Perspect.
PD SEP
PY 2016
VL 10
IS 3
BP 202
EP 207
DI 10.1111/cdep.12186
PG 6
WC Psychology, Developmental
SC Psychology
GA DS7GV
UT WOS:000380952100011
PM 27725843
ER
PT J
AU Vergallo, R
Xing, L
Minami, Y
Soeda, T
Ong, DS
Gao, L
Lee, H
Guagliumi, G
Biasucci, LM
Crea, F
Yu, B
Uemura, S
O'Donnell, CJ
Jang, IK
AF Vergallo, Rocco
Xing, Lei
Minami, Yoshiyasu
Soeda, Tsunenari
Ong, Daniel S.
Gao, Lei
Lee, Hang
Guagliumi, Giulio
Biasucci, Luigi M.
Crea, Filippo
Yu, Bo
Uemura, Shiro
O'Donnell, Christopher J.
Jang, Ik-Kyung
TI Associations between the Framingham Risk Score and coronary plaque
characteristics as assessed by three-vessel optical coherence tomography
SO CORONARY ARTERY DISEASE
LA English
DT Article
DE coronary artery disease; Framingham Risk Score; optical coherence
tomography
ID INTRAVASCULAR ULTRASOUND; ATHEROSCLEROTIC PLAQUE; HEART-DISEASE;
ETHNIC-GROUPS; PROGRESSION; ARTERY; CALCIFICATION; BURDEN; VALIDATION;
PREDICTION
AB Objectives This study sought to explore the association between the Framingham Risk Score (FRS) and coronary plaque characteristics assessed by optical coherence tomography (OCT) imaging.
Background Clinical prediction models are useful for identifying high-risk patients. However, coronary events often occur in individuals estimated to be at low risk.
Methods A total of 254 patients with coronary artery disease who underwent three-vessel OCT were divided into tertiles according to FRS. Nonculprit plaque characteristics were compared among the three groups.
Results A total of 663 plaques were analyzed. FRS was significantly associated with calcification [37% (low FRS) vs. 46% (intermediate FRS) vs. 70% (high FRS); P<0.001] and neovascularization [39% (low FRS) vs. 41% (intermediate FRS) vs. 56% (high FRS); P<0.001], but not with lipid-rich plaques or thin-cap fibroatheroma (TCFA). On multivariate analysis, FRS was an independent predictor of the presence of both calcification and neovascularization. There were no deaths, two acute myocardial infarctions, and 15 nontarget lesion revascularizations at the 1-year followup. The event rate increased progressively across FRS tertiles [2.4% (low FRS) vs. 7.1% (intermediate FRS) vs. 8.6% (high FRS); P=0.186]. The c-statistic for FRS to predict future clinical events was 0.628 (95% confidence interval, 0.500-0.757). The addition of both calcification and TCFA to FRS provided incremental prognostic value [c-statistics: 0.761 (95% confidence interval, 0.631-0.890)].
Conclusion The present study showed significant associations between FRS and the presence of coronary calcification and neovascularization in nonculprit plaques. The combination of FRS and OCT-detected calcifications and TCFA provides improved prognostic ability in identifying patients with known coronary artery disease who are at risk of recurrent events. Copyright (C) 2016 Wolters Kluwer Health, Inc. All rights reserved.
C1 [Vergallo, Rocco; Xing, Lei; Minami, Yoshiyasu; Soeda, Tsunenari; Ong, Daniel S.; Gao, Lei; O'Donnell, Christopher J.; Jang, Ik-Kyung] Harvard Med Sch, Massachusetts Gen Hosp, Div Cardiol, GRB 800,55 Fruit St, Boston, MA 02114 USA.
[Lee, Hang] Harvard Med Sch, Massachusetts Gen Hosp, Biostat Ctr, Boston, MA USA.
[O'Donnell, Christopher J.] NHLBI, Framingham Heart Study, Framingham, MA USA.
[Xing, Lei; Yu, Bo] Harbin Med Univ, Dept Cardiol, Affiliated Hosp 2, Harbin, Peoples R China.
[Guagliumi, Giulio] Osped Papa Giovanni XXIII, Cardiovasc Dept, Bergamo, Italy.
[Biasucci, Luigi M.; Crea, Filippo] Univ Cattolica Sacro Cuore, Dept Cardiovasc Med, Rome, Italy.
[Uemura, Shiro] Nara Med Univ, Dept Cardiol, Nara, Japan.
[Jang, Ik-Kyung] Kyung Hee Univ, Div Cardiol, Seoul, South Korea.
RP Jang, IK (reprint author), Harvard Med Sch, Massachusetts Gen Hosp, Div Cardiol, GRB 800,55 Fruit St, Boston, MA 02114 USA.
EM ijang@mgh.harvard.edu
FU Michael and Kathryn Park; Gill and Allan Gray; St Jude Medical; Italian
Society of Cardiology Award for Research Abroad and the 'Enrico ed
Enrica Sovena' Foundation, Rome, Italy
FX Dr Jang's research was supported by Michael and Kathryn Park, and by
Gill and Allan Gray. Dr Jang has received grants and consulting fees
from St Jude Medical. Dr Vergallo was supported by the 2013 Italian
Society of Cardiology Award for Research Abroad and the 'Enrico ed
Enrica Sovena' Foundation, Rome, Italy. For the remaining authors there
are no conflicts of interest.
NR 28
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U1 2
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0954-6928
EI 1473-5830
J9 CORONARY ARTERY DIS
JI Coronary Artery Dis.
PD SEP
PY 2016
VL 27
IS 6
BP 460
EP 466
DI 10.1097/MCA.0000000000000383
PG 7
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA DS5FI
UT WOS:000380806300005
PM 27218146
ER
PT J
AU Lewandowski, LB
Kaplan, MJ
AF Lewandowski, Laura B.
Kaplan, Mariana J.
TI Update on cardiovascular disease in lupus
SO CURRENT OPINION IN RHEUMATOLOGY
LA English
DT Review
DE atherosclerosis; cardiovascular disease; interferons; neutrophil
extracellular traps; systemic lupus erythematosus
ID NEUTROPHIL EXTRACELLULAR TRAPS; INTERNATIONAL INCEPTION COHORT;
LOW-DENSITY-LIPOPROTEIN; 25-HYDROXYVITAMIN D DEFICIENCY;
POPULATION-BASED COHORT; CORONARY-HEART-DISEASE; RISK-FACTORS;
SUBCLINICAL ATHEROSCLEROSIS; ENDOTHELIAL DYSFUNCTION; METABOLIC SYNDROME
AB Purpose of review
Atherosclerotic cardiovascular disease confers significant morbidity and mortality in patients with systemic lupus erythematosus (SLE) and cannot be fully explained by traditional cardiovascular risk factors. Recent immunologic discoveries have outlined putative pathways in SLE that may also accelerate the development of atherosclerosis.
Recent findings
Aberrant innate and adaptive immune responses implicated in lupus pathogenesis may also contribute to the development of accelerated atherosclerosis in these patients. Defective apoptosis, abnormal lipoprotein function, autoantibodies, aberrant neutrophil responses, and a dysregulated type I interferon pathway likely contribute to endothelial dysfunction. SLE macrophages have an inflammatory phenotype that may drive progression of plaque.
Summary
Recent discoveries have placed increased emphasis on the immunology of atherosclerotic cardiovascular disease. Understanding the factors that drive the increased risk for cardiovascular disease in SLE patients may provide selective therapeutic targets for reducing inflammation and improving outcomes in atherosclerosis.
C1 [Lewandowski, Laura B.; Kaplan, Mariana J.] NIAMSD, Syst Autoimmun Branch, NIH, Bethesda, MD 20892 USA.
RP Kaplan, MJ (reprint author), NIAMS, Syst Autoimmun Branch, NIH, 10 Ctr Dr,6D47C, Bethesda, MD 20892 USA.
EM Mariana.kaplan@nih.gov
FU NIAMS/NIH; Lupus Research Institute
FX This work was supported by the Intramural Research Program, NIAMS/NIH
and the Lupus Research Institute.
NR 114
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U1 10
U2 12
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1040-8711
EI 1531-6963
J9 CURR OPIN RHEUMATOL
JI Curr. Opin. Rheumatol.
PD SEP
PY 2016
VL 28
IS 5
BP 460
EP 468
DI 10.1097/BOR.0000000000000307
PG 9
WC Rheumatology
SC Rheumatology
GA DS5AS
UT WOS:000380793500002
ER
PT J
AU Janssen, I
Chen, CC
Millo, CM
Ling, A
Taieb, D
Lin, FI
Adams, KT
Wolf, KI
Herscovitch, P
Fojo, AT
Buchmann, I
Kebebew, E
Pacak, K
AF Janssen, Ingo
Chen, Clara C.
Millo, Corina M.
Ling, Alexander
Taieb, David
Lin, Frank I.
Adams, Karen T.
Wolf, Katherine I.
Herscovitch, Peter
Fojo, Antonio T.
Buchmann, Inga
Kebebew, Electron
Pacak, Karel
TI PET/CT comparing Ga-68-DOTATATE and other radiopharmaceuticals and in
comparison with CT/MRI for the localization of sporadic metastatic
pheochromocytoma and paraganglioma
SO EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
LA English
DT Article
DE Ga-68-DOTATATE; F-18-FDG; Pheochromocytoma; Paraganglioma; Metastatic
ID POSITRON-EMISSION-TOMOGRAPHY; I-123-MIBG SPECT; TUMORS; SDHB; DIAGNOSIS;
CANCER; HEAD; NEUROENDOCRINE; METAANALYSIS; SUPERIORITY
AB Pheochromocytomas/paragangliomas (PPGLs) and their metastases are tumors that predominantly express somatostatin receptor 2 (SSR2). Ga-68-DOTA(0)-Tyr(3)-octreotate (Ga-68-DOTATATE) is a PET radiopharmaceutical with both high and selective affinity for SSRs. The purpose of this study was to evaluate the utility of Ga-68-DOTATATE in comparison with other specific and nonspecific radiopharmaceuticals recommended in the current guidelines for the localization of metastatic sporadic PPGL by PET/CT.
This prospective study included 22 patients (15 men, 7 women; aged 50.0 +/- 13.9 years) with confirmed metastatic PPGL, a negative family history for PPGL, and negative genetic testing, who underwent Ga-68-DOTATATE, F-18-fluoro-2-deoxy-D-glucose (F-18-FDG) PET/CT, and CT/MRI. Only 12 patients underwent an additional F-18-fluorodihydroxyphenylalanine (F-18-FDOPA) PET/CT scan and only 11 patients underwent an additional F-18-fluorodopamine (F-18-FDA) PET/CT scan. The rates of detection of metastatic lesions were compared among all the imaging studies. A composite of all functional and anatomical imaging studies served as the imaging comparator.
Ga-68-DOTATATE PET/CT showed a lesion-based detection rate of 97.6 % (95 % confidence interval, CI, 95.8 - 98.7 %). F-18-FDG PET/CT, F-18-FDOPA PET/CT, F-18-FDA PET/CT, and CT/MRI showed detection rates of 49.2 % (CI 44.5 - 53.6 %; p < 0.01), 74.8 % (CI 69.0 - 79.9 %); p < 0.01), 77.7 % (CI 71.5 - 82.8 %; p < 0.01), and 81.6 % (CI 77.8 - 84.8 %; p < 0.01), respectively.
The results of this study demonstrate the superiority of Ga-68-DOTATATE PET/CT in the localization of sporadic metastatic PPGLs compared to all other functional and anatomical imaging modalities, and suggest modification of future guidelines towards this new imaging modality.
C1 [Janssen, Ingo; Adams, Karen T.; Wolf, Katherine I.; Pacak, Karel] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Adult & Reprod Endocrinol, NIH, Bldg 10,CRC,Room 1E-3140,10 Ctr Dr MSC 1109, Bethesda, MD 20892 USA.
[Janssen, Ingo; Buchmann, Inga] Univ Hosp Schleswig Holstein, Nucl Med Sect, Dept Radiol & Nucl Med, Campus Lubeck,Ratzeburger Allee 160, D-23538 Lubeck, Germany.
[Chen, Clara C.] NIH, Nucl Med Div Radiol & Imaging Sci, Ctr Clin, Bethesda, MD 20892 USA.
[Millo, Corina M.; Herscovitch, Peter] NIH, Positron Emiss Tomog Dept, Ctr Clin, Bethesda, MD 20892 USA.
[Ling, Alexander] NIH, Radiol & Imaging Sci, Ctr Clin, Bethesda, MD 20892 USA.
[Taieb, David] Aix Marseille Univ, La Timone Univ Hosp, Dept Nucl Med, CERIMED, Marseille, France.
[Lin, Frank I.] NCI, Canc Imaging Program, NIH, Bethesda, MD 20892 USA.
[Fojo, Antonio T.] NCI, Endocrine Oncol Branch, Bethesda, MD 20892 USA.
[Kebebew, Electron] NCI, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Pacak, K (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Adult & Reprod Endocrinol, NIH, Bldg 10,CRC,Room 1E-3140,10 Ctr Dr MSC 1109, Bethesda, MD 20892 USA.
EM karel@mail.nih.gov
FU Intramural Research Program of the National Institutes of Health, Eunice
Kennedy Shriver National Institute of Child Health and Human Development
FX This work was supported, in part, by the Intramural Research Program of
the National Institutes of Health, Eunice Kennedy Shriver National
Institute of Child Health and Human Development.
NR 37
TC 2
Z9 2
U1 8
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 SEP
PY 2016
VL 43
IS 10
BP 1784
EP 1791
DI 10.1007/s00259-016-3357-x
PG 8
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA DS3RJ
UT WOS:000380700100005
PM 26996779
ER
PT J
AU Melo, DR
Miller, DL
Chang, L
Moroz, B
Linet, MS
Simon, SL
AF Melo, Dunstana R.
Miller, Donald L.
Chang, Lienard
Moroz, Brian
Linet, Martha S.
Simon, Steven L.
TI ORGAN DOSES FROM DIAGNOSTIC MEDICAL RADIOGRAPHY-TRENDS OVER EIGHT
DECADES (1930 TO 2010)
SO HEALTH PHYSICS
LA English
DT Article
DE diagnostic radiology; dose; absorbed; epidemiology; radiation; medical
ID X-RAY EXAMINATIONS; ACTIVE BONE-MARROW; COMPUTED RADIOGRAPHY; CHEST
RADIOGRAPHY; NATIONWIDE EVALUATION; PATIENT DOSIMETRY; RADIATION RISKS;
UNITED-STATES; RADIOLOGY; POPULATION
AB This study provides a retrospective assessment of doses to 13 organs for the most common radiographic examinations conducted between the 1930s and 2010, taking into account typical technical parameters used for radiography during those years. This study is intended to be a resource on changes in medical diagnostic radiation exposure over time with a specific purpose of supporting retrospective epidemiological studies of radiation health risks. The authors derived organ doses to the brain, esophagus, thyroid, red bone marrow, lungs, breast, heart, stomach, liver, colon, urinary bladder, ovaries, and testes based on 14 common radiographic procedures and compared, when possible, with doses reported in the literature. These dose estimates were based on radiographic exposure parameters described in textbooks widely used by radiologic technologists in training from 1939 to 2010. The derived estimated doses presented here are believed to be representative of typical organs for an average-size adult who might be considered to be similar to the reference person. There were large variations in organ doses noted among the different types of radiographic examinations. Doses were highest in organs within the area imaged and next highest in organs in close proximity to the area imaged. Estimated organ doses have declined substantially [overall 22-fold (+/- 38)] over time as a consequence of changes in technology, imaging protocols and protective measures. For some examinations, only slight differences were observed in doses for the decades of the 1960s, 1970s, and 1980s due to minor changes in technical parameters. Substantial dose reductions were observed in the 1990s and 2000s.
C1 [Melo, Dunstana R.] NCI, DCEG, NIH, Bethesda, MD 20892 USA.
[Melo, Dunstana R.] Melohill Technol, Rockville, MD USA.
[Miller, Donald L.] US FDA, Silver Spring, MD USA.
[Chang, Lienard; Moroz, Brian; Linet, Martha S.; Simon, Steven L.] NCI, DCEG, Bethesda, MD 20892 USA.
RP Melo, DR (reprint author), 1 Res Court,Suite 450, Rockville, MD 20850 USA.
EM dunstana.melo@melohilltech.com
FU Intramural Research Program of the National Cancer Institute, National
Institutes of Health
FX This work was supported by the Intramural Research Program of the
National Cancer Institute, National Institutes of Health. We express our
appreciation to Alice Sigurdson (NCI, retired) for encouragement,
insight and support and to Charles Myers of the Division of Radiological
Health, Center for Devices and Radiological Health, Food and Drug
Administration for his assistance in defining radiography fields for
examinations conducted in past decades.
NR 75
TC 0
Z9 0
U1 2
U2 4
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 SEP
PY 2016
VL 111
IS 3
BP 235
EP 255
DI 10.1097/HP.0000000000000524
PG 21
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 DS4PX
UT WOS:000380764100001
PM 27472750
ER
PT J
AU Wiener, L
Viola, A
Kearney, J
Mullins, LL
Sherman-Bien, S
Zadeh, S
Farkas-Patenaude, A
Pao, M
AF Wiener, Lori
Viola, Adrienne
Kearney, Julia
Mullins, Larry L.
Sherman-Bien, Sandra
Zadeh, Sima
Farkas-Patenaude, Andrea
Pao, Maryland
CA Lone Parent Study Grp
TI Impact of Caregiving for a Child With Cancer on Parental Health
Behaviors, Relationship Quality, and Spiritual Faith: Do Lone Parents
Fare Worse?
SO JOURNAL OF PEDIATRIC ONCOLOGY NURSING
LA English
DT Article
DE health behavior; pediatric cancer; caregivers; psychosocial; spiritual
faith; relationships
ID PEDIATRIC CANCER; MOTHERS; STRESS; SINGLE; LIFE; FATHERS; CARE
AB Caregiving stress has been associated with changes in the psychological and physical health of parents of children with cancer, including both partnered and single parents. While parents who indicate single on a demographic checklist are typically designated as single parents, a parent can be legally single and still have considerable support caring for an ill child. Correspondingly, an individual can be married/partnered and feel alone when caring for a child with serious illness. In the current study, we report the results from our exploratory analyses of parent self-reports of behavior changes during their child's treatment. Parents (N = 263) of children diagnosed with cancer were enrolled at 10 cancer centers. Parents reported significant worsening of all their own health behaviors surveyed, including poorer diet and nutrition, decreased physical activity, and less time spent engaged in enjoyable activities 6 to 18 months following their child's diagnosis. More partnered parents found support from friends increased or stayed the same since their child's diagnosis, whereas a higher proportion of lone parents reported relationships with friends getting worse. More lone parents reported that the quality of their relationship with the ill child's siblings had gotten worse since their child's diagnosis. Spiritual faith increased for all parents.
C1 [Wiener, Lori; Viola, Adrienne; Zadeh, Sima] NCI, Pediat Oncol Branch, Bldg 10,Room 1-6466, Bethesda, MD 20892 USA.
[Viola, Adrienne] Rutgers Robert Wood Johnson Med Sch, Newark, NJ USA.
[Kearney, Julia] Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA.
[Mullins, Larry L.] Oklahoma State Univ, Coll Arts & Sci, Dept Psychol, Psychol, Stillwater, OK 74078 USA.
[Mullins, Larry L.] Oklahoma State Univ, Coll Arts & Sci, Res, Stillwater, OK 74078 USA.
[Sherman-Bien, Sandra] Miller Childrens Hosp, Jonathan Jaques Childrens Canc Ctr, Long Beach, CA USA.
[Farkas-Patenaude, Andrea] Dana Farber Canc Inst, Psychol Res Serv, Boston, MA 02115 USA.
[Farkas-Patenaude, Andrea] Dana Farber Canc Inst, Clin Serv, Boston, MA 02115 USA.
[Pao, Maryland] NIMH, Bethesda, MD 20892 USA.
RP Wiener, L (reprint author), NCI, Pediat Oncol Branch, Bldg 10,Room 1-6466, Bethesda, MD 20892 USA.
EM wienerl@nih.gov
FU National Cancer Institute; National Institute of Mental Health
intramural programs of the National Institutes of Health
FX The author(s) disclosed receipt of the following financial support for
the research, authorship, and/or publication of this article: This work
is supported [in part] by the National Cancer Institute and the National
Institute of Mental Health intramural programs of the National
Institutes of Health. This funding supported the design and conduct of
the study; the collection, management, analysis, and interpretation of
the data; preparation, review, and approval of the article; and the
decision to submit the article for publication. The Andre Sobel River of
Life Foundation contributed the gift cards for the study
participants.hD; and Sean Phipps, PhD.
NR 24
TC 0
Z9 0
U1 5
U2 5
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1043-4542
EI 1532-8457
J9 J PEDIATR ONCOL NURS
JI J. Pediatr. Oncol. Nurs.
PD SEP-OCT
PY 2016
VL 33
IS 5
BP 378
EP 386
DI 10.1177/1043454215616610
PG 9
WC Oncology; Nursing
SC Oncology; Nursing
GA DS7JV
UT WOS:000380960700007
PM 26668211
ER
PT J
AU Saposnik, G
Cohen, LG
Mamdani, M
Pooyania, S
Ploughman, M
Cheung, D
Shaw, J
Hall, J
Nord, P
Dukelow, S
Nilanont, Y
De los Rios, F
Olmos, L
Levin, M
Teasell, R
Cohen, A
Thorpe, K
Laupacis, A
Bayley, M
AF Saposnik, Gustavo
Cohen, Leonardo G.
Mamdani, Muhammad
Pooyania, Sepideth
Ploughman, Michelle
Cheung, Donna
Shaw, Jennifer
Hall, Judith
Nord, Peter
Dukelow, Sean
Nilanont, Yongchai
De los Rios, Felipe
Olmos, Lisandro
Levin, Mindy
Teasell, Robert
Cohen, Ashley
Thorpe, Kevin
Laupacis, Andreas
Bayley, Mark
CA Stroke Outcomes Res Canada
TI Efficacy and safety of non-immersive virtual reality exercising in
stroke rehabilitation (EVREST): a randomised, multicentre, single-blind,
controlled trial
SO LANCET NEUROLOGY
LA English
DT Article
ID MOTOR FUNCTION-TEST; UPPER-LIMB; REGIONAL BURDEN; CLINICAL-TRIAL; GLOBAL
BURDEN; SURVIVORS; RECOVERY; IMPAIRMENT; MOVEMENT; DISEASE
AB Background Non-immersive virtual reality is an emerging strategy to enhance motor performance for stroke rehabilitation. There has been rapid adoption of non-immersive virtual reality as a rehabilitation strategy despite the limited evidence about its safety and effectiveness. Our aim was to compare the safety and efficacy of virtual reality with recreational therapy on motor recovery in patients after an acute ischaemic stroke.
Methods In this randomised, controlled, single-blind, parallel-group trial we enrolled adults (aged 18-85 years) who had a first-ever ischaemic stroke and a motor deficit of the upper extremity score of 3 or more (measured with the Chedoke-McMaster scale) within 3 months of randomisation from 14 in-patient stroke rehabilitation units from four countries (Canada [11], Argentina [1], Peru [1], and Thailand [1]). Participants were randomly allocated (1: 1) by a computer-generated assignment at enrolment to receive a programme of structured, task-oriented, upper extremity sessions (ten sessions, 60 min each) of either non-immersive virtual reality using the Nintendo Wii gaming system (VRWii) or simple recreational activities (playing cards, bingo, Jenga, or ball game) as add-on therapies to conventional rehabilitation over a 2 week period. All investigators assessing outcomes were masked to treatment assignment. The primary outcome was upper extremity motor performance measured by total time to complete the Wolf Motor Function Test (WMFT) at the end of the 2 week intervention period, analysed in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NTC01406912.
Findings The study was done between May 12, 2012, and Oct 1, 2015. We randomly assigned 141 patients: 71 received VRWii therapy and 70 received recreational activity. 121 (86%) patients (59 in the VRWii group and 62 in the recreational activity group) completed the final assessment and were included in the primary analysis. Each group improved WMFT performance time relative to baseline (decrease in median time from 43.7 s [IQR 26.1-68.0] to 29.7 s [21.4-45.2], 32.0% reduction for VRWii vs 38.0 s [IQR 28.0-64.1] to 27.1 s [21.2-45.5], 28.7% reduction for recreational activity). Mean time of conventional rehabilitation during the trial was similar between groups (VRWii, 373 min [SD 322] vs recreational activity, 397 min [345]; p=0.70) as was the total duration of study intervention (VRWii, 528 min [SD 155] vs recreational activity, 541 min [142]; p=0.60). Multivariable analysis adjusted for baseline WMFT score, age, sex, baseline Chedoke-McMaster, and stroke severity revealed no signifi cant diff erence between groups in the primary outcome (adjusted mean estimate of diff erence in WMFT: 4.1 s, 95% CI -14.4 to 22.6). There were three serious adverse events during the trial, all deemed to be unrelated to the interventions (seizure after discharge and intracerebral haemorrhage in the recreational activity group and heart attack in the VRWii group). Overall incidences of adverse events and serious adverse events were similar between treatment groups.
Interpretation In patients who had a stroke within the 3 months before enrolment and had mild-to-moderate upper extremity motor impairment, non-immersive virtual reality as an add-on therapy to conventional rehabilitation was not superior to a recreational activity intervention in improving motor function, as measured by WMFT. Our study suggests that the type of task used in motor rehabilitation post-stroke might be less relevant, as long as it is intensive enough and task-specifi c. Simple, low-cost, and widely available recreational activities might be as eff ective as innovative non-immersive virtual reality technologies.
C1 [Saposnik, Gustavo] Univ Toronto, St Michaels Hosp, Div Neurol, Toronto, ON M5C 1R6, Canada.
[Saposnik, Gustavo; Cheung, Donna] Univ Toronto, St Michaels Hosp, Stroke Program, Toronto, ON M5C 1R6, Canada.
[Cohen, Leonardo G.] NINDS, Human Cort Physiol & Stroke Neurorehabil Sect, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
[Saposnik, Gustavo; Mamdani, Muhammad; Hall, Judith; Cohen, Ashley; Thorpe, Kevin; Laupacis, Andreas] St Michaels Hosp, Li Ka Shing Knowledge Inst, Toronto, ON, Canada.
[Pooyania, Sepideth] Riverview Hlth Ctr, Winnipeg, MB, Canada.
[Ploughman, Michelle] Mem Univ, Miller Ctr, St John, NF, Canada.
[Shaw, Jennifer; Bayley, Mark] Univ Toronto, UHN Toronto Rehabil Inst, Toronto, ON M5C 1R6, Canada.
[Nord, Peter] Providence Healthcare, Toronto, ON, Canada.
[Dukelow, Sean] Foothills Med Ctr, Calgary, AB, Canada.
[Nilanont, Yongchai] Mahidol Univ, Siriraj Hosp, Bangkok, Thailand.
[De los Rios, Felipe] Hosp Nacl Cayetano Heredia, Lima, Peru.
[Olmos, Lisandro] Escobar, FLENI Rehabil Inst, Buenos Aires, DF, Argentina.
[Levin, Mindy] McGill Univ, CRIR Res Ctr, Jewish Rehabil Hosp, Montreal, PQ, Canada.
[Teasell, Robert] Univ Western Ontario, Parkwood Inst, London, ON, Canada.
RP Saposnik, G (reprint author), Univ Toronto, Stroke Outcomes Res & Virtual Real Ctr, Stroke Outcome Res Canada Working Grp, St Michaels Hosp,Dept Med, 55 Queen St E, Toronto, ON M5C 1R6, Canada.
EM saposnikg@smh.ca
OI Dukelow, Sean/0000-0002-0609-981X
FU South East Toronto Stroke Network
FX The authors are indebted to all participants of the EVREST trial. We are
very grateful to allied health members at each site who were
instrumental for the successful implementation of EVREST. The authors
would like to thank co-operative students at Li Ka Shing Knowledge
Institute for their assistance with database development and data entry.
The authors thank Sarah Blanton and Steven Wolf for the facilitation of
the training video and suggestions regarding the analysis of the WMFT.
The authors are most grateful for the initial funding provided by South
East Toronto Stroke Network and to Jacqueline Willems for the
unconditional support with the early organisation of the study design
and coordination.
NR 34
TC 2
Z9 2
U1 20
U2 33
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1474-4422
EI 1474-4465
J9 LANCET NEUROL
JI Lancet Neurol.
PD SEP
PY 2016
VL 15
IS 10
BP 1019
EP 1027
DI 10.1016/S1474-4422(16)30121-1
PG 9
WC Clinical Neurology
SC Neurosciences & Neurology
GA DT1ZJ
UT WOS:000381280300018
PM 27365261
ER
PT J
AU Goldstein, DS
Jinsmaa, Y
Sullivan, P
Holmes, C
Kopin, IJ
Sharabi, Y
AF Goldstein, David S.
Jinsmaa, Yunden
Sullivan, Patti
Holmes, Courtney
Kopin, Irwin J.
Sharabi, Yehonatan
TI 3,4-Dihydroxyphenylethanol (Hydroxytyrosol) Mitigates the Increase in
Spontaneous Oxidation of Dopamine During Monoamine Oxidase Inhibition in
PC12 Cells
SO NEUROCHEMICAL RESEARCH
LA English
DT Article
DE Hydroxytyrosol; DOPET; DOPAL; Cysteinyl-dopamine; Monoamine oxidase;
Parkinson's disease
ID OLIVE OIL; RED WINE; DISEASES; ADDUCTS; DAMAGE
AB The catecholaldehyde hypothesis predicts that monoamine oxidase (MAO) inhibition should slow the progression of Parkinson's disease, by decreasing production of the autotoxic dopamine metabolite 3,4-dihydroxyphenylacetaldehyde (DOPAL). Inhibiting MAO, however, diverts the fate of cytoplasmic dopamine toward potentially harmful spontaneous oxidation products, indicated by increased 5-S-cysteinyl-dopamine (Cys-DA) levels. 3,4-Dihydroxyphenylethanol (hydroxytyrosol) is an abundant anti-oxidant phenol in constituents of the Mediterranean diet. Whether hydroxytyrosol alters enzymatic or spontaneous oxidation of dopamine has been unknown. Rat pheochromocytoma PC12 cells were incubated with hydroxytyrosol (10 A mu M, 180 min) alone or with the MAO-A inhibitor clorgyline (1 nM) or the MAO-B inhibitors rasagiline or selegiline (0.5 A mu M). Hydroxytyrosol decreased levels of DOPAL by 30 % and Cys-DA by 49 % (p < 0.0001 each). Co-incubation with hydroxytyrosol prevented the increases in Cys-DA seen with all 3 MAO inhibitors. Hydroxytyrosol therefore inhibits both enzymatic and spontaneous oxidation of endogenous dopamine and mitigates the increase in spontaneous oxidation during MAO inhibition.
C1 [Goldstein, David S.; Jinsmaa, Yunden; Sullivan, Patti; Holmes, Courtney; Kopin, Irwin J.; Sharabi, Yehonatan] NINDS, Clin Neurocardiol Sect, CNP, DIR,NIH, 9000 Rockville Pike,Bldg 10 Rm 5N220, Bethesda, MD 20892 USA.
[Sharabi, Yehonatan] Chaim Sheba Med Ctr, Sackler Fac Med, Tel Aviv, Israel.
[Sharabi, Yehonatan] Tel Aviv Univ, Tel Aviv, Israel.
RP Goldstein, DS (reprint author), NINDS, Clin Neurocardiol Sect, CNP, DIR,NIH, 9000 Rockville Pike,Bldg 10 Rm 5N220, Bethesda, MD 20892 USA.
EM goldsteind@ninds.nih.gov
FU Intramural NIH HHS [ZIA NS003125-06, ZIA NS003034-10, Z99 NS999999]
NR 20
TC 1
Z9 1
U1 7
U2 7
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0364-3190
EI 1573-6903
J9 NEUROCHEM RES
JI Neurochem. Res.
PD SEP
PY 2016
VL 41
IS 9
BP 2173
EP 2178
DI 10.1007/s11064-016-1959-0
PG 6
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA DS3XV
UT WOS:000380716900001
PM 27220335
ER
PT J
AU Bolanos-Guzman, CA
Zarate, CA
AF Bolanos-Guzman, Carlos A.
Zarate, Carlos A., Jr.
TI Underrepresented Minorities in Science: ACNP Strives to Increase
Minority Representation and Inclusion
SO NEUROPSYCHOPHARMACOLOGY
LA English
DT Editorial Material
ID ACADEMIC MEDICINE; DISPARITIES; FACULTY
C1 [Bolanos-Guzman, Carlos A.] Texas A&M Univ, Dept Psychol, 3245 TAMU, College Stn, TX 77843 USA.
[Zarate, Carlos A., Jr.] NIMH, Expt Therapeut & Pathophysiol Branch, Bethesda, MD USA.
[Zarate, Carlos A., Jr.] NIMH, Div Intramural Res Program, Sect Neurobiol & Treatment Mood Disorders, Bethesda, MD USA.
RP Bolanos-Guzman, CA (reprint author), Texas A&M Univ, Dept Psychol, 3245 TAMU, College Stn, TX 77843 USA.
EM bolanos-guzman@tamu.edu
NR 17
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 0893-133X
EI 1740-634X
J9 NEUROPSYCHOPHARMACOL
JI Neuropsychopharmacology
PD SEP
PY 2016
VL 41
IS 10
BP 2421
EP 2423
DI 10.1038/npp.2016.71
PG 3
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA DT7FV
UT WOS:000381653400001
PM 27510298
ER
PT J
AU Fedota, JR
Matous, AL
Salmeron, BJ
Gu, H
Ross, TJ
Stein, EA
AF Fedota, John R.
Matous, Allison L.
Salmeron, Betty Jo
Gu, Hong
Ross, Thomas J.
Stein, Elliot A.
TI Insula Demonstrates a Non-Linear Response to Varying Demand for
Cognitive Control and Weaker Resting Connectivity With the Executive
Control Network in Smokers
SO NEUROPSYCHOPHARMACOLOGY
LA English
DT Article
ID FMRI GROUP-ANALYSIS; SMOKING CUES; FUNCTIONAL CONNECTIVITY;
CIGARETTE-SMOKING; PREFRONTAL CORTEX; DEFAULT-MODE; BRAIN; ADDICTION;
NICOTINE; CONFLICT
AB Deficits in cognitive control processes are a primary characteristic of nicotine addiction. However, while network-based connectivity measures of dysfunction have frequently been observed, empirical evidence of task-based dysfunction in these processes has been inconsistent. Here, in a sample of smokers (n = 35) and non-smokers (n = 21), a previously validated parametric flanker task is employed to characterize addiction-related alterations in responses to varying (ie, high, intermediate, and low) demands for cognitive control. This approach yields a demand-response curve that aims to characterize potential non-linear responses to increased demand for control, including insensitivities or lags in fully activating the cognitive control network. We further used task-based differences in activation between groups as seeds for resting-state analysis of network dysfunction in an effort to more closely link prior inconsistencies in task-related activation with evidence of impaired network connectivity in smokers. For both smokers and non-smokers, neuroimaging results showed similar increases in activation in brain areas associated with cognitive control. However, reduced activation in right insula was seen only in smokers and only when processing intermediate demand for cognitive control. Further, in smokers, this task-modulated right insula showed weaker functional connectivity with the superior frontal gyros, a component of the task-positive executive control network These results demonstrate that the neural instantiation of salience attribution in smokers is both more effortful to fully activate and has more difficulty communicating with the exogenous, task-positive, executive control network. Together, these findings further articulate the cognitive control dysfunction associated with smoking and illustrate a specific brain circuit potentially responsible.
C1 [Fedota, John R.; Matous, Allison L.; Salmeron, Betty Jo; Gu, Hong; Ross, Thomas J.; Stein, Elliot A.] NIDA, Neuroimaging Res Branch, Intramural Res Program, NIH, 251 Bayview Blvd, Baltimore, MD 21224 USA.
RP Fedota, JR (reprint author), NIDA, Neuroimaging Res Branch, Intramural Res Program, NIH, 251 Bayview Blvd, Baltimore, MD 21224 USA.
EM john.fedota@nih.gov
RI Salmeron, Betty Jo/M-1793-2016;
OI Salmeron, Betty Jo/0000-0003-1699-9333; Ross, Thomas/0000-0002-7745-3572
FU National Institute on Drug Abuse (NIDA), Intramural Research Program;
FDA grant [NDA13001-001-00000]
FX This study was supported by the National Institute on Drug Abuse (NIDA),
Intramural Research Program and FDA grant NDA13001-001-00000 to EAS. The
authors declare no conflict of interest.
NR 53
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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 SEP
PY 2016
VL 41
IS 10
BP 2557
EP 2565
DI 10.1038/npp.2016.62
PG 9
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA DT7FV
UT WOS:000381653400014
PM 27112116
ER
PT J
AU Wiers, CE
Shokri-Kojori, E
Wong, CT
Abi-Dargham, A
Demiral, SB
Tomasi, D
Wang, GJ
Volkow, ND
AF Wiers, Corinde E.
Shokri-Kojori, Ehsan
Wong, Christopher T.
Abi-Dargham, Anissa
Demiral, Sukru B.
Tomasi, Dardo
Wang, Gene-Jack
Volkow, Nora D.
TI Cannabis Abusers Show Hypofrontality and Blunted Brain Responses to a
Stimulant Challenge in Females but not in Males
SO NEUROPSYCHOPHARMACOLOGY
LA English
DT Article
ID POSITRON-EMISSION-TOMOGRAPHY; NATIONAL EPIDEMIOLOGIC SURVEY;
GLUCOSE-METABOLISM; GENDER-DIFFERENCES; COCAINE ABUSERS; DOPAMINE
TRANSPORTER; RECEPTOR AVAILABILITY; ORBITOFRONTAL CORTEX; ORAL
METHYLPHENIDATE; PREFRONTAL CORTEX
AB The extent to which cannabis is deleterious to the human brain is not well understood. Here, we test whether cannabis abusers (CA) have impaired frontal function and reactivity to dopaminergic signaling, which are fundamental to relapse in addiction. We measured brain glucose metabolism using PET and [F-18]FDG both at baseline (placebo) and after challenge with methylphenidate (MP), a dopamine enhancing drug, in 24 active CA (50% female) and 24 controls (HC; 50% female). Results show that (i) CA had lower baseline glucose metabolism than HC in frontal cortex including anterior cingulate, which was associated with negative emotionality. (ii) MP increased whole-brain glucose metabolism in HC but not in CA; and group by challenge effects were most profound in putamen, caudate, midbrain, thalamus, and cerebellum. In CA, MP-induced metabolic increases in putamen correlated negatively with addiction severity. (id) There were significant gender effects, such that both the group differences at baseline in frontal metabolism and the attenuated regional brain metabolic responses to MP were observed in female CA but not in male CA. As for other drug addictions, reduced baseline frontal metabolism is likely to contribute to relapse in CA. The attenuated responses to MP in midbrain and striatum are consistent with decreased brain reactivity to dopamine stimulation and might contribute to addictive behaviors in CA. The gender differences suggest that females are more sensitive than males to the adverse effects of cannabis in brain.
C1 [Wiers, Corinde E.; Shokri-Kojori, Ehsan; Wong, Christopher T.; Demiral, Sukru B.; Tomasi, Dardo; Wang, Gene-Jack; Volkow, Nora D.] NIAAA, NIH, Bethesda, MD USA.
[Abi-Dargham, Anissa] Columbia Univ, Dept Psychiat, Div Translat Imaging, New York, NY USA.
[Abi-Dargham, Anissa] New York State Psychiat Inst & Hosp, New York, NY USA.
[Volkow, Nora D.] NIDA, NIH, Bethesda, MD USA.
RP Wiers, CE; Volkow, ND (reprint author), NIAAA, Lab Neuroimaging, NIH, 10 Ctr Dr,Room B2L 124, Bethesda, MD 20892 USA.
EM corinde.wiers@nih.gov; nvolkow@nida.nih.gov
FU NIH/NIAAA intramural grant [Y1AA-3009]; German Research Foundation
FX We thank Karen Torres, Barbara Hubbard, Millard Jayne, Yana Studentsova,
Payton King, Pauline Carter, Donald Warner, Joanna Fowler, and Ruben
Baler for their contributions. The work was supported by NIH/NIAAA
intramural grant Y1AA-3009 to NDV. CEW received a scholarship from the
German Research Foundation.
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U1 6
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 SEP
PY 2016
VL 41
IS 10
BP 2596
EP 2605
DI 10.1038/npp.2016.67
PG 10
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA DT7FV
UT WOS:000381653400018
PM 27156854
ER
PT J
AU Alonso, N
Nebreda, AD
Monczor, F
Gutkind, JS
Davio, C
Fernandez, N
Shayo, C
AF Alonso, Natalia
Diaz Nebreda, Antonela
Monczor, Federico
Silvio Gutkind, J.
Davio, Carlos
Fernandez, Natalia
Shayo, Carina
TI PI3K pathway is involved in ERK signaling cascade activation by
histamine H2R agonist in HEK293T cells
SO BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS
LA English
DT Article
DE Histamine H2 receptor; ERK; PI3K; Cell proliferation; Cell signaling
ID BETA-GAMMA-SUBUNITS; LEYDIG TUMOR-CELLS; STRUCTURAL INSTABILITY;
CONSTITUTIVE ACTIVITY; INTERNATIONAL UNION; KINASE ACTIVATION;
COLORECTAL-CANCER; REGULATED KINASES; BREAST-CANCER; RAP GTPASES
AB Background: Histamine, through histamine H2 receptor (H2R), modulates different biological processes, involving the modulation of PI3K/AKT/mTOR and RAS/RAF/MEK/ERK pathways. Many evidences have demonstrated the existence and importance of the crossregulation between these two signaling pathways. The aim of the present work was to determine the molecular mechanisms leading to PI3K and ERK pathways modulation induced by the H2R agonist amthamine and to evaluate the possible interplay between them.
Methods: Phosphorylation levels of ERK and Akt were examined by Western blot in HEK293T cells expressing the human H2R, in the presence of H2R agonist and dominant negative mutants or pharmacological inhibitors of different proteins/pathways. Transcriptional activity assays were assessed to determine SRE activity. Amthamine-mediated cellular proliferation was investigated in MA-10A cells in the presence of PI3K inhibitor.
Results: H2R agonist inhibits PI3K/Akt/mTOR and stimulates Ras/MEK/ERK pathways. Moreover, PI3K/Akt/mTOR signaling inhibition is necessary to achieve H2R mediated ERK activation. In the presence of a constitutive active mutant of Akt, amthamine is not able to mediate ERK activation. This crosstalk affects classical ERK downstream targets such as Elk1 phosphorylation and the transcriptional activity of the SRE, classically associated to proliferation. We further demonstrate that amthamine-induced proliferation in Leydig MA-10 tumor cells, is enhanced by LY294002, a PI3K inhibitor.
Conclusions: These results describe a crosstalk between PI3K/AKT/mTOR and Ras/MEK/ERK pathways induced by H2R stimulation with implications in cell proliferation.
General significance: This work indicates that the modulation of PI3K/AKT/mTOR pathway by H2R in turn regulates Ras/MEK/ERK activation conditioning the proliferative capacity of the cells. (C) 2016 Elsevier B.V. All rights reserved.
C1 [Alonso, Natalia; Diaz Nebreda, Antonela; Shayo, Carina] Consejo Nacl Invest Cient & Tecn, Lab Patol & Farmacol Mol, IBYME, Buenos Aires, DF, Argentina.
[Monczor, Federico; Davio, Carlos; Fernandez, Natalia] Univ Buenos Aires, Fac Farm & Bioquim, Catedra Quim Med, Buenos Aires, DF, Argentina.
[Monczor, Federico; Davio, Carlos; Fernandez, Natalia] UBA CONICET, Fac Farm & Bioquim, Inst Invest Farmacol, ININFA, Junin 956, Buenos Aires, DF, Argentina.
[Silvio Gutkind, J.] NIDR, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA.
[Alonso, Natalia] Ctr Invest Ciencias Vet & Agron, Inst Biotecnol, Inst Nacl Tecnol Agr, Buenos Aires, DF, Argentina.
[Silvio Gutkind, J.] Univ Calif San Diego, Moores Canc Ctr, La Jolla, CA 92093 USA.
RP Shayo, C (reprint author), Inst Biol & Med Expt, Vuelta Obligado 2490, RA-1428 Buenos Aires, DF, Argentina.
EM carinashayo@hotmail.com
FU Agencia Nacional de Promotion Cientifica y Tecnologica [PICT2013-0495,
PICT2013-2050]; CONICET [PIP 2013-562]; Fundacion Rene Baron [002/2016]
FX This work was supported by grants from the Agencia Nacional de Promotion
Cientifica y Tecnologica (PICT2013-0495, -2050), and from CONICET (PIP
2013-562), as well as from Fundacion Rene Baron (002/2016).
NR 53
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U1 0
U2 2
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0304-4165
EI 1872-8006
J9 BBA-GEN SUBJECTS
JI Biochim. Biophys. Acta-Gen. Subj.
PD SEP
PY 2016
VL 1860
IS 9
BP 1998
EP 2007
DI 10.1016/j.bbagen.2016.06.016
PG 10
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA DS2LQ
UT WOS:000380601400018
PM 27316323
ER
PT J
AU Schade, A
Walliser, C
Wist, M
Haas, J
Vatter, P
Kraus, JM
Filingeri, D
Havenith, G
Kestler, HA
Milner, JD
Gierschik, P
AF Schade, Anja
Walliser, Claudia
Wist, Martin
Haas, Jennifer
Vatter, Petra
Kraus, Johann M.
Filingeri, Davide
Havenith, George
Kestler, Hans A.
Milner, Joshua D.
Gierschik, Peter
TI Cool-temperature-mediated activation of phospholipase C-gamma(2) in the
human hereditary disease PLAID
SO CELLULAR SIGNALLING
LA English
DT Article
DE Phospholipase C-gamma(2); lnositol phospholipid; Rac2 GTPase; Split PH
domain; Autoinhibition; Cold temperature sensitivity
ID GAIN-OF-FUNCTION; B-CELL RECEPTOR; PHOSPHORYLATION-INDUCED ACTIVATION;
COMMON VARIABLE IMMUNODEFICIENCY; PLECKSTRIN HOMOLOGY DOMAIN; C-GAMMA
ISOZYMES; CA2+ ENTRY; SIGNALING COMPLEX; FUNCTION MUTATION; MAST-CELLS
AB Deletions in the gene encoding signal-transducing inositol phospholipid-specific phospholipase C-gamma(2) (PLC gamma(2)) are associated with the novel human hereditary disease PLAID (PLC gamma(2)-associated antibody deficiency and immune dysregulation). PLAID is characterized by a rather puzzling concurrence of augmented and diminished functions of the immune system, such as cold urticaria triggered by only minimal decreases in temperature, autoimmunity, and immunodeficiency. Understanding of the functional effects of the genomic alterations at the level of the affected enzyme, PLC gamma(2), is currently lacking. PLC gamma(2) is critically involved in coupling various cell surface receptors to regulation of important functions of immune cells such as mast cells, B cells, monocytes/macrophages, and neutrophils. PLC gamma(2) is unique by carrying three Src (SH) and one split pleckstrin homology domain (spPH) between the two catalytic subdomains (spPHn-SH2n-SH2c-SH3-spPHc). Prevailing evidence suggests that activation of PLC gamma(2) is primarily due to loss of SH-region-mediated autoinhibition and/or enhanced plasma membrane trans location. Here, we show that the two PLAID PLC gamma(2) mutants lacking portions of the SH region are strongly (>100-fold), rapidly, and reversibly activated by cooling by only a few degrees. We found that the mechanism(s) underlying PLCy gamma(2) PLAID mutant activation by cool temperatures is distinct from a mere loss of SH-region-mediated autoinhibition and dependent on both the integrity and the pliability of the spPH domain. The results suggest a new mechanism of PLC gamma activation with unique thermodynamic features and assign a novel regulatory role to its spPH domain. Involvement of this mechanism in other human disease states associated with cooling such as exertional asthma and certain acute coronary events appears an intriguing possibility. (C) 2016 Elsevier Inc. All rights reserved.
C1 [Schade, Anja; Walliser, Claudia; Wist, Martin; Haas, Jennifer; Vatter, Petra; Gierschik, Peter] Univ Ulm, Med Ctr, Inst Pharmacol & Toxicol, D-89070 Ulm, Germany.
[Kraus, Johann M.; Kestler, Hans A.] Univ Ulm, Inst Med Syst Biol, D-89081 Ulm, Germany.
[Filingeri, Davide; Havenith, George] Univ Loughborough, Environm Ergon Res Ctr, Loughborough LE11 3TU, Leics, England.
[Milner, Joshua D.] NIAID, Allerg Inflammat Unit, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA.
[Filingeri, Davide] Univ Calif Berkeley, Ctr Environm Design Res, Berkeley, CA 94720 USA.
RP Gierschik, P (reprint author), Univ Ulm, Med Ctr, Inst Pharmacol & Toxicol, Albert Einstein Allee 11, D-89081 Ulm, Germany.
EM peter.gierschik@uni-ulm.de
FU Deutsche Forschungsgemeinschaft (DFG) [SFB 1074, TP A8]; SFB [1074]; DFG
Research Training Group [GRK1041]; International Graduate School in
Molecular Medicine Ulm (IGradU) within the Excellence Initiative of the
German Federal and State Governments [GSC 279]
FX Work in P.G.'s laboratory is funded by grants from the Deutsche
Forschungsgemeinschaft (DFG) (SFB 1074, TP A8). The contribution of J.K.
and H.K. was supported by project Z1 of SFB 1074. A.S. was a fellow of
the DFG Research Training Group GRK1041 and the International Graduate
School in Molecular Medicine Ulm (IGradU) funded within the Excellence
Initiative of the German Federal and State Governments (GSC 279).
NR 66
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U1 2
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0898-6568
EI 1873-3913
J9 CELL SIGNAL
JI Cell. Signal.
PD SEP
PY 2016
VL 28
IS 9
BP 1237
EP 1251
DI 10.1016/j.cellsig.2016.05.010
PG 15
WC Cell Biology
SC Cell Biology
GA DS2JJ
UT WOS:000380595500011
PM 27196803
ER
PT J
AU Singh, N
Kumar, R
Engwerda, C
Sacks, D
Nylen, S
Sundar, S
AF Singh, Neetu
Kumar, Rajiv
Engwerda, Christian
Sacks, David
Nylen, Susanne
Sundar, Shyam
TI Tumor necrosis factor alpha neutralization has no direct effect on
parasite burden, but causes impaired IFN-gamma production by spleen
cells from human visceral leishmaniasis patients
SO CYTOKINE
LA English
DT Article
DE Visceral leishmaniasis; TNF-alpha; Enbrel; IL-10; Splenic aspirate;
Whole blood assay
ID OF-THE-LITERATURE; MICE LACKING TNF; CUTANEOUS LEISHMANIASIS; T-CELLS;
RHEUMATOID-ARTHRITIS; INFECTIOUS-DISEASES; FACTOR THERAPY; RECEPTOR P55;
NITRIC-OXIDE; IN-VIVO
AB The pro-inflammatory cytokine tumor necrosis factor (TNF)-alpha has an important role in control of experimental Leishmania donovani infection. Less is known about the role of TNF-alpha in human visceral leishmaniasis (VL). Evidence for a protective role is primarily based on case reports of VL development in individuals treated with TNF-alpha neutralizing antibody. In this study, we have evaluated how TNF-alpha neutralization affects parasite replication and cytokine production in ex vivo splenic aspirates (SA) from active VL patients. The effect of TNF-alpha neutralization on cell mediated antigen specific responses were also evaluated using whole blood cultures. Neutralization of TNF-alpha did not affect parasite numbers in SA cultures. Interferon (IFN)-gamma levels were significantly reduced, but interleukin (IL)-10 levels were unchanged in these cultures. Leishmania antigen stimulated SA produced significant TNF-alpha which suggests that TNF-alpha is actively produced in VL spleen. Further it stimulates IFN-gamma production, but no direct effect on parasite replication. (C) 2016 Elsevier Ltd. All rights reserved.
C1 [Singh, Neetu; Sundar, Shyam] Banaras Hindu Univ, Dept Med, Inst Med Sci, Varanasi 221005, Uttar Pradesh, India.
[Kumar, Rajiv] Netaji Subhas Inst Technol, Div Biotechnol, New Delhi 110078, India.
[Engwerda, Christian] QIMR Berghofer Med Res Inst, Immunol & Infect Lab, Herston, Qld 4006, Australia.
[Sacks, David] NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Nylen, Susanne] Karolinska Inst, Dept Microbiol, Stockholm, Sweden.
[Kumar, Rajiv] Banaras Hindu Univ, Dept Biochem, Varanasi 221005, Uttar Pradesh, India.
RP Sundar, S (reprint author), Banaras Hindu Univ, Dept Med, Inst Med Sci, Varanasi 221005, Uttar Pradesh, India.; Kumar, R (reprint author), Banaras Hindu Univ, Dept Biochem, Varanasi 221005, Uttar Pradesh, India.
EM rajiv082@yahoo.com; drshyamsundar@hotmail.com
FU Extramural Research Program of the National Institute of Allergy and
Infectious Diseases (NIAID), National Institutes of Health (NIH)
Tropical Medicine Research Centers [TMRC Grant] [IP50 AI074321];
UGC-CSIR, New Delhi, India
FX This work was supported by the Extramural Research Program of the
National Institute of Allergy and Infectious Diseases (NIAID), National
Institutes of Health (NIH) Tropical Medicine Research Centers [TMRC
Grant No. IP50 AI074321]. Neetu Singh is funded by UGC-CSIR, New Delhi,
India.
NR 46
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Z9 0
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 SEP
PY 2016
VL 85
BP 184
EP 190
DI 10.1016/j.cyto.2016.06.013
PG 7
WC Biochemistry & Molecular Biology; Cell Biology; Immunology
SC Biochemistry & Molecular Biology; Cell Biology; Immunology
GA DS2JO
UT WOS:000380596000029
PM 27372917
ER
PT J
AU Jackson, JP
Li, LH
Chamberlain, ED
Wang, HB
Ferguson, SS
AF Jackson, Jonathan P.
Li, Linhou
Chamberlain, Erica D.
Wang, Hongbing
Ferguson, Stephen S.
TI Contextualizing Hepatocyte Functionality of Cryopreserved HepaRG Cell
Cultures
SO DRUG METABOLISM AND DISPOSITION
LA English
DT Article
ID CONSTITUTIVE ANDROSTANE RECEPTOR; FARNESOID-X-RECEPTOR; SALT EXPORT
PUMP; IN-VITRO; CYTOCHROME-P450 ISOFORMS; HEPG2 CELLS; NUCLEAR
TRANSLOCATION; INTRINSIC CLEARANCE; DRUG-METABOLISM; RAT HEPATOCYTES
AB Over the last decade HepaRG cells have emerged as a promising alternative to primary human hepatocytes (PHH) and have been featured in over 300 research publications. Most of these reports employed freshly differentiated HepaRG cells that require time-consuming culture (similar to 28 days) for full differentiation. Recently, a cryopreserved, predifferentiated format of HepaRG cells (termed here "cryo-HepaRG") has emerged as a new model that improves global availability and experimental flexibility; however, it is largely unknown whether HepaRG cells in this format fully retain their hepatic characteristics. Therefore, we systematically investigated the hepatocyte functionality of cryo-HepaRG cultures in context with the range of interindividual variation observed with PHH in both sandwich-culture and suspension formats. These evaluations uncovered a novel adaptation period for the cryo-HepaRG format and demonstrated the impact of extracellular matrix on cryo-HepaRG functionality. Pharmacologically important drug-metabolizing alleles were genotyped in HepaRG cells and poor metabolizer alleles for CYP2D6, CYP2C9, and CYP3A5 were identified and consistent with higher frequency alleles found in individuals of Caucasian decent. We observed liver enzyme inducibility with aryl hydrocarbon receptor, constitutive androstane receptor (CAR), and pregnane X receptor activators comparable to that of sandwich-cultured PHH. Finally, we show for the first time that cryo-HepaRG supports proper CAR cytosolic sequestration and translocation to hepatocyte nuclei in response to phenobarbital treatment. Taken together, these data reveal important considerations for the use of this cell model and demonstrate that cryo-HepaRG are suitable for metabolism and toxicology screening.
C1 [Jackson, Jonathan P.; Chamberlain, Erica D.; Ferguson, Stephen S.] ADME Tox, Cell Syst Div, Life Technol, Durham, NC USA.
[Li, Linhou; Wang, Hongbing] Univ Maryland, Sch Pharm, Dept Pharmaceut Sci, Baltimore, MD 21201 USA.
[Jackson, Jonathan P.] QTS, Durham, NC USA.
[Chamberlain, Erica D.] QPS, Newark, DE USA.
[Ferguson, Stephen S.] NIEHS, Natl Toxicol Program Div, Bethesda, MD USA.
RP Ferguson, SS (reprint author), 111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA.
EM stephen.ferguson@nih.gov
FU Life Technologies (Thermo Fisher) research and development
FX The laboratory research was funded by Life Technologies (Thermo Fisher)
research and development. Resources for data analysis and manuscript
preparation were supported by the National Institutes of Health,
National Institute of Environmental Health Sciences, the National
Toxicology Program Division, and by Qualyst Transporter Solutions, Inc.
NR 43
TC 1
Z9 1
U1 7
U2 9
PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA
SN 0090-9556
EI 1521-009X
J9 DRUG METAB DISPOS
JI Drug Metab. Dispos.
PD SEP
PY 2016
VL 44
IS 9
BP 1463
EP 1479
DI 10.1124/dmd.116.069831
PG 17
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA DS4IA
UT WOS:000380743500005
PM 27338863
ER
PT J
AU Purdue, MP
Silverman, DT
AF Purdue, Mark P.
Silverman, Debra T.
TI Clearing the Air: Summarizing the Smoking-related Relative Risks of
Bladder and Kidney Cancer
SO EUROPEAN UROLOGY
LA English
DT Editorial Material
C1 [Purdue, Mark P.; Silverman, Debra T.] NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
RP Purdue, MP (reprint author), NCI, 9609 Med Ctr Dr,Room 6E602, Rockville, MD 20850 USA.
EM purduem@mail.nih.gov
NR 10
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0302-2838
EI 1873-7560
J9 EUR UROL
JI Eur. Urol.
PD SEP
PY 2016
VL 70
IS 3
BP 467
EP 468
DI 10.1016/j.eururo.2016.04.009
PG 2
WC Urology & Nephrology
SC Urology & Nephrology
GA DS4MA
UT WOS:000380754000023
PM 27130147
ER
PT J
AU Krakow, M
Rogers, B
AF Krakow, Melinda
Rogers, Brian
TI Collateral Damage and Critical Turning Points: Public Health
Implications of HPV Vaccine News Coverage for Boys and Men in 2011
SO HEALTH COMMUNICATION
LA English
DT Article
ID HUMAN-PAPILLOMAVIRUS VACCINATION; PROMISCUITY; NEWSPAPERS; CANCER;
SAMPLE
AB In 2009, the Food and Drug Administration (FDA) officially expanded approval of the Gardasil vaccine to include human papillomavirus (HPV) vaccination for boys and men, and in 2011, the Centers for Disease Control and Prevention (CDC) issued a formal recommendation for routine vaccination for this population. Despite these efforts, HPV vaccination rates for boys and men continue to fall short of public health targets. While news was breaking about the benefits of the HPV vaccine for boys and men, public attention shifted as a result of political debates concerning the vaccine. This study examines a pivotal time period for public health in which the vaccine became officially recommended for boys and men and at the same time became the center of political controversies in the lead-up to the 2012 presidential campaign. The current study extends previous research and presents a content analysis of newspaper articles (N=154) about the HPV vaccine for the year 2011. Results indicate that the lack of comprehensive coverage of HPV and the HPV vaccine found in previous studies continued in this year. Results shed light on key political events that may have functioned to overshadow the recommendation of the HPV vaccine for boys and men. The implications of this pattern of news coverage can inform public health efforts to address low rates of HPV vaccination uptake among boys and men in present day.
C1 [Krakow, Melinda] NCI, Canc Prevent Fellowship Program, 9609 Med Ctr Dr,Room 2W-136, Rockville, MD 20850 USA.
[Rogers, Brian] Univ Utah, Dept Commun, Salt Lake City, UT 84112 USA.
RP Krakow, M (reprint author), NCI, Canc Prevent Fellowship Program, 9609 Med Ctr Dr,Room 2W-136, Rockville, MD 20850 USA.
EM melinda.krakow@nih.gov
NR 21
TC 1
Z9 1
U1 17
U2 17
PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD
PI ABINGDON
PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND
SN 1041-0236
EI 1532-7027
J9 HEALTH COMMUN
JI Health Commun.
PD SEP
PY 2016
VL 31
IS 9
BP 1081
EP 1088
DI 10.1080/10410236.2015.1038773
PG 8
WC Communication; Health Policy & Services
SC Communication; Health Care Sciences & Services
GA DR8LG
UT WOS:000380148800004
PM 26799666
ER
PT J
AU Stolze, BR
Gounden, V
Gu, JH
Elliott, EA
Masika, LS
Abel, BS
Merke, DP
Skarulis, MC
Soldin, SJ
AF Stolze, Brian R.
Gounden, Verena
Gu, Jianghong
Elliott, Elizabeth A.
Masika, Likhona S.
Abel, Brent S.
Merke, Deborah P.
Skarulis, Monica C.
Soldin, Steven J.
TI An improved micro-method for the measurement of steroid profiles by
APPI-LC-MS/MS and its use in assessing diurnal effects on steroid
concentrations and optimizing the diagnosis and treatment of adrenal
insufficiency and CAH
SO JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY
LA English
DT Review
DE Micro-method atmospheric pressure; photoionization LC-MS/MS; Steroids;
Diurnal variation; Dehydroepiandrosterone
ID TANDEM MASS-SPECTROMETRY; LIQUID-CHROMATOGRAPHY; TESTOSTERONE; MEN;
HORMONES; SERUM; HYPERPLASIA; CORTISOL;
5-ALPHA-ANDROSTANE-3-ALPHA,17-BETA-DIOL; RADIOIMMUNOASSAY
AB Our goals were to (1) develop an improved micro-method usable for neonates for steroid profile measurements and a method to measure androsterone, a key steroid in the recently described androgen backdoor pathway together, with dehydroepiandrosterone and (2) to assess if dehydroepiandrosterone diurnal concentration fluctuations exist potentially necessitating strict adherence to time of blood sample draw and requirement of separate time-dependent reference intervals. Liquid chromatography tandem mass spectrometry was performed with an atmospheric pressure photoionization source [1]. For each sample 50 mu L (100 mu L for the backdoor pathway) of serum was deproteinized by adding 75 mu L (150 mu L for the backdoor pathway) of acetonitrile containing the internal standards. After centrifugation, 75 mu L (150 mu L for the backdoor pathway) of supernatant was diluted with 250 mu L of water and injected onto a Poroshell 120 EC-C8 column (SB-C8 column for the backdoor pathway). Within-run coefficients of variation ranged from 2.4 to 10.4% and between-day coefficients of variation from 2.9 to 11.2%. Comparison studies yielded correlation coefficient between 0.97 and 1.00 with recoveries of 90% or greater. Our methods analyze a 9 steroid profile and an additional 2 steroid profile (backdoor pathway) with minimal sample volume (usable in neonates optimizing early diagnosis of endocrinopathies and genetic diseases). Low limits of quantitation make these methods ideal for steroid measurement in women and prepubertal children. As diurnal variations of dehydroepiandrosterone and other steroids [2] concentrations are clinically significant we recommend that separate reference intervals be developed for 8 am, 8 pm, and midnight sample draws. The use of this approach in improving the diagnosis of patients with adrenal insufficiency and congenital adrenal hyperplasia is discussed. Published by Elsevier Ltd.
C1 [Stolze, Brian R.; Gounden, Verena; Gu, Jianghong; Elliott, Elizabeth A.; Masika, Likhona S.; Soldin, Steven J.] NIH, Dept Lab Med, 10 Ctr Dr,Bldg 10,Room 2C-306, Bethesda, MD 20814 USA.
[Abel, Brent S.; Skarulis, Monica C.] NIDDK, NIH, 10Ctr Dr,Bldg 10,Room 6-3940, Bethesda, MD 20814 USA.
[Soldin, Steven J.] Georgetown Univ, Div Endocrinol & Metab, Dept Med, 3700 O St NW, Washington, DC 20057 USA.
[Merke, Deborah P.] NIH, Ctr Clin, 10 Ctr Dr,Bldg 10,Room 1-2740, Bethesda, MD 20814 USA.
[Merke, Deborah P.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, 10 Ctr Dr,Bldg 10,Room 1-2740, Bethesda, MD 20814 USA.
RP Soldin, SJ (reprint author), NIH, Dept Lab Med, 10 Ctr Dr,Bldg 10,Room 2C-306, Bethesda, MD 20814 USA.
EM steven.soldin@nih.gov
OI Elliott, Elizabeth/0000-0001-7743-4526
FU Intramural program of the NIH
FX This research has been supported (in part) by the Intramural program of
the NIH.
NR 32
TC 1
Z9 1
U1 4
U2 6
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0960-0760
J9 J STEROID BIOCHEM
JI J. Steroid Biochem. Mol. Biol.
PD SEP
PY 2016
VL 162
SI SI
BP 110
EP 116
DI 10.1016/j.jsbmb.2015.12.024
PG 7
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA DS1XM
UT WOS:000380418500010
PM 26721696
ER
PT J
AU Tetrault, JM
Tate, JP
Edelman, EJ
Gordon, AJ
Lo Re, V
Lim, JK
Rimland, D
Goulet, J
Crystal, S
Gaither, JR
Gibert, CL
Rodriguez-Barradas, MC
Fiellin, LE
Bryant, K
Justice, AC
Fiellin, DA
AF Tetrault, Jeanette M.
Tate, Janet P.
Edelman, E. Jennifer
Gordon, Adam J.
Lo Re, Vincent, III
Lim, Joseph K.
Rimland, David
Goulet, Joseph
Crystal, Stephen
Gaither, Julie R.
Gibert, Cynthia L.
Rodriguez-Barradas, Maria C.
Fiellin, Lynn E.
Bryant, Kendall
Justice, Amy C.
Fiellin, David A.
TI Hepatic Safety of Buprenorphine in HIV-Infected and Uninfected Patients
With Opioid Use Disorder: The Role of HCV-Infection
SO JOURNAL OF SUBSTANCE ABUSE TREATMENT
LA English
DT Article
DE Buprenorphine; HIV; Hepatitis C; Drug induced liver injury
ID LIVER-ENZYME ELEVATION; DEPENDENT PATIENTS; NALOXONE TREATMENT;
INDIVIDUALS; THERAPY; HEALTH; TRIAL; RISK
AB Introduction: Individuals with HIV and hepatitis C (HCV) infection, alcohol use disorder, or who are prescribed potentially hepatotoxic medications may be at increased risk for buprenorphine (BUP) associated hepatotoxicity.
Materials and methods: We examined a cohort of HIV-infected and uninfected patients receiving an initial BUP prescription between 2003 and 2012. We compared changes in alanine and aspartate aminotransferases (ALT and AST) and total bilirubin (TB) stratified by HIV status. We identified cases of liver enzyme elevation (LEE), TB elevation (TBE), and conducted chart review to assess for cases of drug induced liver injury (DILI) and death. We examined associations between age, sex, race, HIV-infection, HCV-infection, alcohol use disorder, and prescription of other potentially heptatotoxic medications with the composite endpoint of LEE, TBE, and DILI.
Results: Of 666 patients prescribed BUP, 36% were HIV-infected, 98% were male, 60% had RNA-confirmed HCV infection, 50% had a recent diagnosis of alcohol use disorder, and 64% were prescribed other potentially hepatotoxic medications. No clinically significant changes were observed in median ALT, AST and TB and these changes did not differ between HIV-infected and uninfected patients. Compared with uninfected patients, HIV-infected (OR 73, 95% CI 2.1-26.1, p = 0.002), HCV-infected (OR 4.9 95% CI 1.6-15.2, p = 0.007) or HIV/HCV co-infected patients (OR 6.9, 95%CI 2.1-22.2, p = 0.001) were more likely to have the composite endpoint of LEE, TB elevation or DILI, in analyses that excluded 60 patients with evidence of pre-existing liver injury. 31 patients had LEE, 14/187 HIV-infected and 17/340 uninfected (p = 0.25); 11 had TBE, including 9/186 HIV-infected and 2/329 uninfected (p = 0.002); 8 experienced DILI, 4/202 HIV-infected and 4/204 uninfected (p = 0.45). There were no significant associations with alcohol use disorder or prescription of other potentially hepatotoxic medications after adjustment for HIV/HCV status.
Conclusions: Liver enzymes and TB are rarely elevated in HIV-infected and uninfected patients receiving BUP. Risk of hepatotoxicity was greater in individuals infected with HIV, HCV, or HIV/HCV co-infection, who may benefit from increased monitoring. (C) 2016 Elsevier Inc. All rights reserved.
C1 [Tetrault, Jeanette M.; Tate, Janet P.; Edelman, E. Jennifer; Lim, Joseph K.; Fiellin, Lynn E.; Justice, Amy C.; Fiellin, David A.] Yale Univ, Sch Med, Dept Internal Med, New Haven, CT 06510 USA.
[Tate, Janet P.; Lim, Joseph K.; Justice, Amy C.] VA Connecticut Hlth Care Syst, West Haven, CT USA.
[Gordon, Adam J.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA.
[Gordon, Adam J.] Univ Pittsburgh, Pittsburgh, PA USA.
[Lo Re, Vincent, III] Univ Penn, Sch Med, Philadelphia, PA 19104 USA.
[Rimland, David] VA Med Ctr, Atlanta, GA USA.
[Rimland, David] Emory Univ, Sch Med, Atlanta, GA USA.
[Goulet, Joseph] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA.
[Crystal, Stephen] Rutgers State Univ, Inst Hlth, Ctr Hlth Serv Res, New Brunswick, NJ USA.
[Gaither, Julie R.; Justice, Amy C.; Fiellin, David A.] Yale Univ, Sch Publ Hlth, Ctr Interdisciplinary Res AIDS, New Haven, CT USA.
[Gibert, Cynthia L.] VA Med Ctr, Washington, DC USA.
[Gibert, Cynthia L.] George Washington Univ, Sch Med & Hlth Sci, Washington, DC 20052 USA.
[Rodriguez-Barradas, Maria C.] Michael E DeBakey VA Med Ctr, Houston, TX USA.
[Rodriguez-Barradas, Maria C.] Baylor Coll, Sch Med, Houston, TX USA.
[Bryant, Kendall] NIAAA, Bethesda, MD USA.
RP Tetrault, JM (reprint author), 367 Cedar St,Suite 305, New Haven, CT 06510 USA.
EM jeanette.tetrault@yale.edu
OI Fiellin, David/0000-0002-4006-010X; Goulet, Joseph/0000-0002-0842-804X
FU Department of Veterans Affairs, Veterans Health Administration, and
Office of Research and Development; [U10 AA013566]; [U24 AA020794];
[U01 AA020790]; [U19 HS021112]; [R01 HS018372]
FX This material is based upon work supported by the Department of Veterans
Affairs, Veterans Health Administration, and Office of Research and
Development We must disclaim that the views expressed in this article
are those of the authors and do not necessarily reflect the position or
policy of the Department of Veterans Affairs.; Supported by. U10
AA013566, U24 AA020794, U01 AA020790, U19 HS021112, R01 HS018372
NR 25
TC 0
Z9 0
U1 0
U2 0
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0740-5472
J9 J SUBST ABUSE TREAT
JI J. Subst. Abus. Treat.
PD SEP
PY 2016
VL 68
BP 62
EP 67
DI 10.1016/j.jsat.2016.06.002
PG 6
WC Psychology, Clinical; Substance Abuse
SC Psychology; Substance Abuse
GA DS2GB
UT WOS:000380579300008
PM 27431048
ER
PT J
AU Strickland, J
Zang, QD
Kleinstreuer, N
Paris, M
Lehmann, DM
Choksi, N
Matheson, J
Jacobs, A
Lowit, A
Allen, D
Casey, W
AF Strickland, Judy
Zang, Qingda
Kleinstreuer, Nicole
Paris, Michael
Lehmann, David M.
Choksi, Neepa
Matheson, Joanna
Jacobs, Abigail
Lowit, Anna
Allen, David
Casey, Warren
TI Integrated decision strategies for skin sensitization hazard
SO JOURNAL OF APPLIED TOXICOLOGY
LA English
DT Article
DE skin sensitization; allergic contact dermatitis; integrated decision
strategy; machine learning; LLNA; DPRA; KeratinoSens; h-CLAT; support
vector machine
ID LYMPH-NODE ASSAY; LINE ACTIVATION TEST; TEST H-CLAT; SCREENING CONTACT
ALLERGENS; PEPTIDE REACTIVITY ASSAY; NONANIMAL TEST METHODS; PIG
MAXIMIZATION TEST; RISK-ASSESSMENT MODEL; IN-VITRO METHODS; PREDICTIVE
PERFORMANCE
AB One of the top priorities of the Interagency Coordinating Committee for the Validation of Alternative Methods (ICCVAM) is the identification and evaluation of non-animal alternatives for skin sensitization testing. Although skin sensitization is a complex process, the key biological events of the process have been well characterized in an adverse outcome pathway (AOP) proposed by the Organisation for Economic Co-operation and Development (OECD). Accordingly, ICCVAM is working to develop integrated decision strategies based on the AOP using in vitro, in chemico and in silico information. Data were compiled for 120 substances tested in the murine local lymph node assay (LLNA), direct peptide reactivity assay (DPRA), human cell line activation test (h-CLAT) and KeratinoSens assay. Data for six physicochemical properties, which may affect skin penetration, were also collected, and skin sensitization read-across predictions were performed using OECD QSAR Toolbox. All data were combined into a variety of potential integrated decision strategies to predict LLNA outcomes using a training set of 94 substances and an external test set of 26 substances. Fifty-four models were built using multiple combinations of machine learning approaches and predictor variables. The seven models with the highest accuracy (89-96% for the test set and 96-99% for the training set) for predicting LLNA outcomes used a support vector machine (SVM) approach with different combinations of predictor variables. The performance statistics of the SVM models were higher than any of the non-animal tests alone and higher than simple test battery approaches using these methods. These data suggest that computational approaches are promising tools to effectively integrate data sources to identify potential skin sensitizers without animal testing. Published 2016. This article has been contributed to by US Government employees and their work is in the public domain in the USA.
The Interagency Coordinating Committee for the Validation of Alternative Methods (ICCVAM) evaluated a non-animal decision strategies to predict skin sensitization. Machine learning approaches integrated in vitro, in chemico and in silico data and six physicochemical properties for 120 substances to predict murine local lymph node assay (LLNA) outcomes. The seven models with the highest accuracy used a support vector machine with different combinations of predictor variables. The models outperformed individual non-animal methods and test batteries. This suggests that computational approaches are promising tools to effectively integrate data to identify potential skin sensitizers without animal testing.
C1 [Strickland, Judy; Zang, Qingda; Kleinstreuer, Nicole; Paris, Michael; Choksi, Neepa; Allen, David] ILS, Res Triangle Pk, NC 27709 USA.
[Lehmann, David M.] US EPA, NHEERL, EPHD, CIB, Res Triangle Pk, NC 27709 USA.
[Matheson, Joanna] US Consumer Prod Safety Commiss, Bethesda, MD 20814 USA.
[Jacobs, Abigail] US FDA, CDER, Silver Spring, MD 20993 USA.
[Lowit, Anna] US EPA, OCSPP, OPP, HED, Washington, DC 20460 USA.
[Casey, Warren] NIEHS, NIH, DNTP, NICEATM, Res Triangle Pk, NC 27709 USA.
RP Casey, W (reprint author), NIEHS, NIH, DNTP, NICEATM, POB 12233, Res Triangle Pk, NC 27709 USA.
EM warren.casey@nih.gov
OI Kleinstreuer, Nicole/0000-0002-7914-3682
FU federal funds from the NIEHS, NIH of NICEATM [HHSN273201500010C]
FX The authors thank Drs D. Germolec, B.A. Merrick, R. Luebke and M. Ward
for their thoughtful critical review of this manuscript. This project
was funded in whole or in part with federal funds from the NIEHS, NIH
under contract HHSN273201500010C to ILS in support of NICEATM.
NR 77
TC 8
Z9 8
U1 3
U2 10
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0260-437X
EI 1099-1263
J9 J APPL TOXICOL
JI J. Appl. Toxicol.
PD SEP
PY 2016
VL 36
IS 9
BP 1150
EP 1162
DI 10.1002/jat.3281
PG 13
WC Toxicology
SC Toxicology
GA DR5PD
UT WOS:000379954000008
PM 26851134
ER
PT J
AU He, ZJ
Wan, XM
Schulz, A
Bludau, H
Dobrovolskaia, MA
Stern, ST
Montgomery, SA
Yuan, H
Li, ZB
Alakhova, D
Sokolsky, M
Darr, DB
Perou, CM
Jordan, R
Luxenhofer, R
Kabanov, AV
AF He, Zhijian
Wan, Xiaomeng
Schulz, Anita
Bludau, Herdis
Dobrovolskaia, Marina A.
Stern, Stephan T.
Montgomery, Stephanie A.
Yuan, Hong
Li, Zibo
Alakhova, Dania
Sokolsky, Marina
Darr, David B.
Perou, Charles M.
Jordan, Rainer
Luxenhofer, Robert
Kabanov, Alexander V.
TI A high capacity polymeric micelle of paclitaxel: Implication of high
dose drug therapy to safety and in vivo anti-cancer activity
SO BIOMATERIALS
LA English
DT Article
DE Polyoxazolines; Paclitaxel nanoformulation; In vitro; In vivo; Efficacy;
Multi-drug resistant cancer
ID BREAST-CANCER; DELIVERY-SYSTEMS; NANOPARTICLE FORMULATION;
CREMOPHOR-FREE; PHASE-II; POLY(2-OXAZOLINE); EFFICACY; TUMORS; NK105;
TAXOL
AB The poor solubility of paclitaxel (PTX), the commercially most successful anticancer drug, has long been hampering the development of suitable formulations. Here, we present translational evaluation of a nanoformulation of PTX, which is characterized by a facile preparation, extraordinary high drug loading of 50% wt. and PTX solubility of up to 45 g/L, excellent shelf stability and controllable, sub-100 nm size. We observe favorable in vitro and in vivo safety profiles and a higher maximum tolerated dose compared to clinically approved formulations. Pharmacokinetic analysis reveals that the higher dose administered leads to a higher exposure of the tumor to PTX. As a result, we observed improved therapeutic outcome in orthotopic tumor models including particularly faithful and aggressive "T11" mouse claudin-low breast cancer orthotopic, syngeneic transplants. The promising preclinical data on the presented PTX nanoformulation showcase the need to investigate new excipients and is a robust basis to translate into clinical trials. (C) 2016 Elsevier Ltd. All rights reserved.
C1 [He, Zhijian; Wan, Xiaomeng; Alakhova, Dania; Sokolsky, Marina; Kabanov, Alexander V.] Univ N Carolina, Eshelman Sch Pharm, Ctr Nanotechnol Drug Delivery, Genet Med Bldg,Room 1094,Campus Box 7362, Chapel Hill, NC 27599 USA.
[He, Zhijian; Wan, Xiaomeng; Alakhova, Dania; Sokolsky, Marina; Kabanov, Alexander V.] Univ N Carolina, Eshelman Sch Pharm, Div Mol Pharmaceut, Chapel Hill, NC 27599 USA.
[Schulz, Anita; Bludau, Herdis; Jordan, Rainer] Tech Univ Dresden, Dept Chem, Makromol Chem, Mommsenstr 4, D-01069 Dresden, Germany.
[Dobrovolskaia, Marina A.; Stern, Stephan T.] Leidos Biomed Res Inc, Nanotechnol Characterizat Lab, Frederick Natl Lab Canc Res, Frederick, MD USA.
[Montgomery, Stephanie A.] Univ N Carolina, Dept Pathol & Lab Med, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA.
[Yuan, Hong; Li, Zibo] Univ N Carolina, Sch Med, Dept Radiol, Chapel Hill, NC 27599 USA.
[Darr, David B.; Perou, Charles M.] Univ N Carolina, Anim Study Core, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA.
[Luxenhofer, Robert] Univ Wurzburg, Funct Polymer Mat, Chair Chem Technol Mat Synth, Rontgenring 11, D-97070 Wurzburg, Germany.
[Kabanov, Alexander V.] Moscow MV Lomonosov State Univ, Lab Chem Design Bionanomat, Fac Chem, Moscow, Russia.
RP Kabanov, AV (reprint author), Univ N Carolina, Eshelman Sch Pharm, Ctr Nanotechnol Drug Delivery, Genet Med Bldg,Room 1094,Campus Box 7362, Chapel Hill, NC 27599 USA.; Luxenhofer, R (reprint author), Univ Wurzburg, Funct Polymer Mat, Chair Chem Technol Mat Synth, Rontgenring 11, D-97070 Wurzburg, Germany.
EM robert.luxenhofer@uni-wuerzburg.de; kabanov@email.unc.edu
RI Jordan, Rainer/B-6542-2008; Nanotechnology Characterization Lab,
NCL/K-8454-2012; Luxenhofer, Robert/C-2825-2008
OI Jordan, Rainer/0000-0002-9414-1597; Luxenhofer,
Robert/0000-0001-5567-7404
FU Cancer Nanotechnology Platform Partnership grant of the National Cancer
Institute Alliance for Nanotechnology in Cancer [U01 CA116591]; UNC
Eshelman School of Pharmacy; University Cancer Research Fund through the
Lineberger Comprehensive Cancer Center; NCI Breast SPORE program
[P50-CA58223-09A1]; [RO1-CA148761]
FX This work was supported by a Cancer Nanotechnology Platform Partnership
grant (U01 CA116591) of the National Cancer Institute Alliance for
Nanotechnology in Cancer awarded to A.V.K. and the The Carolina
Partnership, a strategic partnership between the, UNC Eshelman School of
Pharmacy and The University Cancer Research Fund through the Lineberger
Comprehensive Cancer Center. C.M.P was supported by NCI Breast SPORE
program (P50-CA58223-09A1), and RO1-CA148761.
NR 45
TC 6
Z9 6
U1 44
U2 96
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0142-9612
EI 1878-5905
J9 BIOMATERIALS
JI Biomaterials
PD SEP
PY 2016
VL 101
BP 296
EP 309
DI 10.1016/j.biomaterials.2016.06.002
PG 14
WC Engineering, Biomedical; Materials Science, Biomaterials
SC Engineering; Materials Science
GA DR0YJ
UT WOS:000379632500027
PM 27315213
ER
PT J
AU Liu, LJ
Fissel, JA
Tasnim, A
Borzan, J
Gocke, A
Calabresi, PA
Farah, MH
AF Liu, Lijuan
Fissel, John A.
Tasnim, Aniqa
Borzan, Jasenka
Gocke, Anne
Calabresi, Peter A.
Farah, Mohamed H.
TI Increased TNFR1 expression and signaling in injured peripheral nerves of
mice with reduced BACE1 activity
SO NEUROBIOLOGY OF DISEASE
LA English
DT Article
DE Neuroinflammation; Macrophages in the PNS; Nervous system injury
ID NECROSIS-FACTOR-ALPHA; MOUSE SCIATIC-NERVE; IMMUNE-MEDIATED
DEMYELINATION; CHRONIC CONSTRICTION INJURY; AMYLOID PRECURSOR PROTEIN;
BETA-SECRETASE BACE1; WALLERIAN DEGENERATION; FUNCTIONAL RECOVERY;
CYTOKINE EXPRESSION; AXON REGENERATION
AB Hematogenous macrophages remove myelin debris from injured peripheral nerves to provide a micro environment conducive to axonal regeneration. Previously, we observed that injured peripheral nerves from Beta-site APP Cleaving Enzyme 1 (BACE1) knockout (KO) mice displayed earlier influx of and enhanced phagocytosis by macrophages when compared to wild-type (WT) mice. These observations suggest that BACE1 might regulate macrophage influx into distal stumps of injured nerves. To determine through which pathway BACE1 influences macrophage influx, we used a mouse inflammation antibody array to assay the expression of inflammation-related proteins in injured nerves of BACE1 KO and WT mice. The most significant change was in expression of tumor necrosis factor receptor 1 (TNFR1) in the distal stump of injured BACE1 KO nerves. Western blotting of protein extracts confirmed increased expression of TNFR1 and its downstream transcriptional factor NF kappa B in the BACE1 KO distal stumps. Additionally, treatment of WT mice with a BACE1 inhibitor resulted in increased TNFR1 expression and signaling in the distal stump of injured nerves. Exogenous TNF alpha increased nuclear translocation of p65 NF kappa B in BACE1 KO tissue and cultured fibroblasts compared with control WT. BACE1 regulates TNFR1 expression at the level of gene expression and not through proteolytic processing. The accelerated macrophage influx in injured nerves of BACE1 KO mice correlates with increased expression and signaling via TNFR1, indicating a link between BACE1 activity and TNFR1 expression/signaling that might contribute to repair of the injured nervous system. (C) 2016 Elsevier Inc All rights reserved.
C1 [Liu, Lijuan; Fissel, John A.; Tasnim, Aniqa; Gocke, Anne; Calabresi, Peter A.; Farah, Mohamed H.] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA.
[Borzan, Jasenka] Johns Hopkins Univ, Sch Med, Dept Anesthesiol & Crit Care Med, Baltimore, MD 21205 USA.
[Tasnim, Aniqa] Harvard Univ, Cambridge, MA 02138 USA.
[Borzan, Jasenka] NIH, Bldg 10, Bethesda, MD 20892 USA.
RP Farah, MH (reprint author), Johns Hopkins Univ, Sch Med, Dept Neurol, Neuromuscular Div, John G Rangos Sr Bldg,Room 239,855 N Wolfe St, Baltimore, MD 21205 USA.
EM mfarah2@jhmi.edu
FU Muscular Dystrophy Association [MDA 254860]; National Institutes of
Neurological Disease and Stroke of the National Institutes of Health
[R01NS079339]
FX This work was supported by the Muscular Dystrophy Association (MDA
254860) and R01NS079339 from the National Institutes of Neurological
Disease and Stroke of the National Institutes of Health. We thank Carol
Cooke, Justin Glenn, Lori Lebson, Zoe Rammelkamp, and Parisa
Moghaddam-Taaheri for technical assistance.
NR 53
TC 1
Z9 1
U1 7
U2 10
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 SEP
PY 2016
VL 93
BP 21
EP 27
DI 10.1016/j.nbd.2016.04.002
PG 7
WC Neurosciences
SC Neurosciences & Neurology
GA DQ8IE
UT WOS:000379452600003
PM 27080468
ER
PT J
AU Srivastava, S
Reid, BJ
Ghosh, S
Kramer, BS
AF Srivastava, Sudhir
Reid, Brian J.
Ghosh, Sharmistha
Kramer, Barnett S.
TI Research Needs for Understanding the Biology of Overdiagnosis in Cancer
Screening
SO JOURNAL OF CELLULAR PHYSIOLOGY
LA English
DT Review
ID PROSTATE-CANCER; BREAST-CANCER; FOLLOW-UP; BARRETTS-ESOPHAGUS;
EVOLUTION; MUTATIONS; CELLS; ADENOCARCINOMA; KERATINOCYTES; MAMMOGRAPHY
AB Many cancers offer an extended window of opportunity for early detection and therapeutic intervention that could lead to a reduction in cause-specific mortality. The pursuit of early detection in screening settings has resulted in decreased incidence and mortality for some cancers (e.g., colon and cervical cancers), and increased incidence with only modest or no effect on cause-specific mortality in others (e.g., breast and prostate). Whereas highly sensitive screening technologies are better at detecting a number of suspected "cancers" that are indolent and likely to remain clinically unimportant in the lifetime of a patient, defined as overdiagnosis, they often miss cancers that are aggressive and tend to present clinically between screenings, known as interval cancers. Unrecognized overdiagnosis leads to overtreatment with its attendant (often long-lasting) side effects, anxiety, and substantial financial harm. Existing methods often cannot differentiate indolent lesions from aggressive ones or understand the dynamics of neoplastic progression. To correctly identify the population that would benefit the most from screening and identify the lesions that would benefit most from treatment, the evolving genomic and molecular profiles of individual cancers during the clinical course of progression or indolence must be investigated, while taking into account an individual's genetic susceptibility, clinical and environmental risk factors, and the tumor microenvironment. Practical challenges lie not only in the lack of access to tissue specimens that are appropriate for the study of natural history, but also in the absence of targeted research strategies. This commentary summarizes the recommendations from a diverse group of scientists with expertise in basic biology, translational research, clinical research, statistics, and epidemiology and public health professionals convened to discuss research directions. (C) 2015 Wiley Periodicals, Inc.
C1 [Srivastava, Sudhir; Ghosh, Sharmistha; Kramer, Barnett S.] NCI, Canc Prevent Div, NIH, 9609 Med Ctr Dr, Bethesda, MD 20892 USA.
[Reid, Brian J.] Univ Washington, Fred Hutchinson Canc Res Ctr, Dept Genome Sci, Div Human Biol, Seattle, WA 98195 USA.
[Reid, Brian J.] Univ Washington, Fred Hutchinson Canc Res Ctr, Dept Genome Sci, Div Publ Hlth Sci, Seattle, WA 98195 USA.
[Reid, Brian J.] Univ Washington, Fred Hutchinson Canc Res Ctr, Dept Med, Div Human Biol, Seattle, WA 98195 USA.
Univ Washington, Fred Hutchinson Canc Res Ctr, Dept Med, Div Publ Hlth Sci, Seattle, WA 98195 USA.
RP Srivastava, S (reprint author), NCI, Canc Prevent Div, NIH, 9609 Med Ctr Dr, Bethesda, MD 20892 USA.
EM srivasts@mail.nih.gov
FU NCI NIH HHS [P01 CA091955]
NR 51
TC 3
Z9 3
U1 3
U2 26
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0021-9541
EI 1097-4652
J9 J CELL PHYSIOL
JI J. Cell. Physiol.
PD SEP
PY 2016
VL 231
IS 9
BP 1870
EP 1875
DI 10.1002/jcp.25227
PG 6
WC Cell Biology; Physiology
SC Cell Biology; Physiology
GA DQ4FJ
UT WOS:000379159100004
PM 26505642
ER
PT J
AU Salinas, AG
Davis, MI
Lovinger, DM
Mateo, Y
AF Salinas, Armando G.
Davis, Margaret I.
Lovinger, David M.
Mateo, Yolanda
TI Dopamine dynamics and cocaine sensitivity differ between striosome and
matrix compartments of the striatum
SO NEUROPHARMACOLOGY
LA English
DT Article
DE Patch; Voltammetry; Nucleus accumbens; Dopamine transporter; Dopamine D2
receptor
ID SIZED SPINY NEURONS; CAT CAUDATE-NUCLEUS; RAT STRIATUM; DORSAL STRIATUM;
CHOLINERGIC INTERNEURONS; PROJECTION SYSTEMS; SINGLE-AXON; RELEASE;
ACCUMBENS; HETEROGENEITY
AB The striatum is typically classified according to its major output pathways, which consist of dopamine D1 and D2 receptor-expressing neurons. The striatum is also divided into striosome and matrix compartments, based on the differential expression of a number of proteins, including the mu opioid receptor, dopamine transporter (DAT), and Nr4a1 (nuclear receptor subfamily 4, group A, member 1). Numerous functional differences between the striosome and matrix compartments are implicated in dopamine related neurological disorders including Parkinson's disease and addiction. Using Nr4a1-eGFP mice, we provide evidence that electrically evoked dopamine release differs between the striosome and matrix compartments in a regionally-distinct manner. We further demonstrate that this difference is not due to differences in inhibition of dopamine release by dopamine autoreceptors or nicotinic acetylcholine receptors. Furthermore, cocaine enhanced extracellular dopamine in striosomes to a greater degree than in the matrix and concomitantly inhibited dopamine uptake in the matrix to a greater degree than in striosomes. Importantly, these compartment differences in cocaine sensitivity were limited to the dorsal striatum. These findings demonstrate a level of exquisite microanatomical regulation of dopamine by the DAT in striosomes relative to the matrix. Published by Elsevier Ltd.
C1 [Salinas, Armando G.] George Mason Univ, Krasnow Inst Adv Study, Fairfax, VA 22030 USA.
[Salinas, Armando G.; Davis, Margaret I.; Lovinger, David M.; Mateo, Yolanda] NIAAA, Lab Integrat Neurosci, Sect Synapt Pharmacol, Rockville, MD 20852 USA.
RP Mateo, Y (reprint author), NIAAA, Lab Integrat Neurosci, Sect Synapt Pharmacol, NIH, 5625 Fishers Lane, Rockville, MD 20852 USA.
EM mateoy@mail.nih.gov
FU NIAAA [R01 AA016022]; National Institutes of Health, National Institute
on Alcohol Abuse and Alcoholism, Division of Intramural Clinical and
Biomedical Research [ZIA AA000407]
FX This work was supported by NIAAA R01 AA016022 (AGS) and the National
Institutes of Health, National Institute on Alcohol Abuse and
Alcoholism, Division of Intramural Clinical and Biomedical Research
(MID, YM, and DML) (Grant Number: ZIA AA000407).
NR 59
TC 4
Z9 4
U1 4
U2 14
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0028-3908
EI 1873-7064
J9 NEUROPHARMACOLOGY
JI Neuropharmacology
PD SEP
PY 2016
VL 108
BP 275
EP 283
DI 10.1016/j.neuropharm.2016.03.049
PG 9
WC Neurosciences; Pharmacology & Pharmacy
SC Neurosciences & Neurology; Pharmacology & Pharmacy
GA DQ1IA
UT WOS:000378953500027
PM 27036891
ER
PT J
AU Kocarnik, JM
Chan, AT
Slattery, ML
Potter, JD
Meyerhardt, J
Phipps, A
Nan, HM
Harrison, T
Rohan, TE
Qi, LH
Hou, LF
Caan, B
Kroenke, CH
Strickler, H
Hayes, RB
Schoen, RE
Chong, DQ
White, E
Berndt, SI
Peters, U
Newcomb, PA
AF Kocarnik, Jonathan M.
Chan, Andrew T.
Slattery, Martha L.
Potter, John D.
Meyerhardt, Jeffrey
Phipps, Amanda
Nan, Hongmei
Harrison, Tabitha
Rohan, Thomas E.
Qi, Lihong
Hou, Lifang
Caan, Bette
Kroenke, Candyce H.
Strickler, Howard
Hayes, Richard B.
Schoen, Robert E.
Chong, Dawn Q.
White, Emily
Berndt, Sonja I.
Peters, Ulrike
Newcomb, Polly A.
TI Relationship of prediagnostic body mass index with survival after
colorectal cancer: Stage-specific associations
SO INTERNATIONAL JOURNAL OF CANCER
LA English
DT Article
DE body mass index (BMI); cancer stage; colorectal cancer (CRC); mortality;
survival
ID OBESITY PARADOX; WOMENS HEALTH; COLON-CANCER; SUSCEPTIBILITY LOCI;
PROSPECTIVE COHORT; PHYSICAL-ACTIVITY; MORTALITY; DIAGNOSIS; OVERWEIGHT;
DEATH
AB Higher body mass index (BMI) is a well-established risk factor for colorectal cancer (CRC), but is inconsistently associated with CRC survival. In 6 prospective studies participating in the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO), 2,249 non-Hispanic white CRC cases were followed for a median 4.5 years after diagnosis, during which 777 died, 554 from CRC-related causes. Associations between prediagnosis BMI and survival (overall and CRC-specific) were evaluated using Cox regression models adjusted for age at diagnosis, sex, study and smoking status (current/former/never). The association between BMI category and CRC survival varied by cancer stage at diagnosis (I-IV) for both all-cause (p-interaction=0.03) and CRC-specific mortality (p-interaction=0.04). Compared to normal BMI (18.5-24.9 kg/m(2)), overweight (BMI 25.0-29.9) was associated with increased mortality among those with Stage I disease, and decreased mortality among those with Stages II-IV disease. Similarly, obesity (BMI >= 30) was associated with increased mortality among those with Stages I-II disease, and decreased mortality among those with Stages III-IV disease. These results suggest the relationship between BMI and survival after CRC diagnosis differs by stage at diagnosis, and may emphasize the importance of adequate metabolic reserves for colorectal cancer survival in patients with late-stage disease.
C1 [Kocarnik, Jonathan M.; Phipps, Amanda; White, Emily; Peters, Ulrike; Newcomb, Polly A.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
[Kocarnik, Jonathan M.; Potter, John D.; Phipps, Amanda; Harrison, Tabitha; White, Emily; Peters, Ulrike; Newcomb, Polly A.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, 1124 Columbia St, Seattle, WA 98104 USA.
[Chan, Andrew T.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA.
[Chan, Andrew T.; Chong, Dawn Q.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA.
[Slattery, Martha L.] Univ Utah, Dept Internal Med, Hlth Sci Ctr, Salt Lake City, UT 84112 USA.
[Meyerhardt, Jeffrey] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Meyerhardt, Jeffrey] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA.
[Nan, Hongmei] Indiana Univ, Richard M Fairbanks Sch Publ Hlth, Dept Epidemiol, Indianapolis, IN 46204 USA.
[Nan, Hongmei] Indiana Univ, Melvin & Bren Simon Canc Ctr, Indianapolis, IN 46204 USA.
[Rohan, Thomas E.] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA.
[Qi, Lihong] Univ Calif Davis, Sch Med, Dept Publ Hlth Sci, Davis, CA 95616 USA.
[Hou, Lifang] Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, Chicago, IL 60611 USA.
[Hou, Lifang] Northwestern Univ, Feinberg Sch Med, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA.
[Caan, Bette; Kroenke, Candyce H.] Kaiser Permanente No Calif, Div Res, Oakland, CA USA.
[Hayes, Richard B.] NYU, Div Epidemiol, Sch Med, New York, NY USA.
[Schoen, Robert E.] Univ Pittsburgh, Med Ctr, Dept Med & Epidemiol, Pittsburgh, PA USA.
[Chong, Dawn Q.] Natl Canc Ctr Singapore, Div Med Oncol, Singapore, Singapore.
[Berndt, Sonja I.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
RP Kocarnik, JM (reprint author), Kocarnik 1100 Fairview Ave N Mailstop M4-B402, Seattle, WA 98199 USA.
EM jkocarni@fredhutch.org
OI Hayes, Richard/0000-0002-0918-661X; Kocarnik,
Jonathan/0000-0001-8084-1608
FU National Center for Advancing Translational Sciences (National
Institutes of Health) [KL2 TR000421]; National Cancer Institute [K05
CA152715, T32 CA 09168, U01 CA137088, R01 CA059045, P01 CA055075, UM1
CA167552, R01 CA137178, R01 CA151993, P50 CA127003, UM1 CA186107, P01
CA87969, R01 CA042182, K05 CA154337]; Division of Cancer Epidemiology;
Division of Cancer Prevention (PLCO); National Heart, Lung, and Blood
Institute, National Institutes of Health [HHSN268201100046C,
HHSN268201100001C, HHSN268201100002C, HHSN268201100003C,
HHSN268201100004C, HHSN271201100004C]
FX Grant sponsor: National Center for Advancing Translational Sciences
(National Institutes of Health); Grant number: KL2 TR000421; Grant
sponsor: National Cancer Institute; Grant numbers: K05 CA152715, T32 CA
09168; U01 CA137088 and R01 CA059045 (GECCO); P01 CA055075, UM1
CA167552, R01 CA137178, R01 CA151993 and P50 CA127003 (HPFS); UM1
CA186107, R01 CA137178, P01 CA87969, R01 CA151993 and P50 CA127003
(NHS); R01 CA042182 (PHS); K05 CA154337 (VITAL); Intramural Research
Program of the Division of Cancer Epidemiology and contracts from the
Division of Cancer Prevention (PLCO); Grant sponsor: National Heart,
Lung, and Blood Institute, National Institutes of Health; Grant numbers:
HHSN268201100046C, HHSN268201100001C, HHSN268201100002C,
HHSN268201100003C, HHSN268201100004C and HHSN271201100004C (WHI)
NR 47
TC 2
Z9 2
U1 2
U2 13
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 SEP 1
PY 2016
VL 139
IS 5
BP 1065
EP 1072
DI 10.1002/ijc.30163
PG 8
WC Oncology
SC Oncology
GA DP3TR
UT WOS:000378418800011
PM 27121247
ER
PT J
AU Xi, LF
Schiffman, M
Koutsky, LA
Hughes, JP
Hulbert, A
Shen, ZP
Galloway, DA
Kiviat, NB
AF Xi, Long Fu
Schiffman, Mark
Koutsky, Laura A.
Hughes, James P.
Hulbert, Ayaka
Shen, Zhenping
Galloway, Denise A.
Kiviat, Nancy B.
TI Variant-specific persistence of infections with human papillomavirus
Types 31, 33, 45, 56 and 58 and risk of cervical intraepithelial
neoplasia
SO INTERNATIONAL JOURNAL OF CANCER
LA English
DT Article
DE human papillomavirus; variants; persistence; cervical intraepithelial
neoplasia
ID NATURAL-HISTORY; YOUNG-WOMEN; LESIONS; HPV; POLYMORPHISM; POPULATION;
CANCER; COHORT; CLASSIFICATION
AB In our previous study of the etiologic role of oncogenic human papillomavirus (HPV) types other than HPV16 and 18, we observed a significantly higher risk of cervical intraepithelial neoplasia Grades 2-3 (CIN2/3) associated with certain lineages of HPV types 31/33/45/56/58 [called high-risk (HR) variants] compared with non-HR variants. This study was to examine whether these intra-type variants differ in persistence of the infection and persistence-associated risk of CIN2/3. Study subjects were women who had any of HPV types 31/33/45/56/58 newly detected during a 2-year follow-up with 6-month intervals. For each type, the first positive sample was used for variant characterization. The association of reverting-to-negativity with group of the variants and CIN2/3 with length of positivity was assessed using discrete Cox regression and logistic regression, respectively. Of the 598 newly detected, type-specific HPV infections, 312 became undetectable during follow-up. Infections with HR, compared with non-HR, variants were marginally more likely to become negative [adjusted hazard ratio=1.3; 95% confidence interval (CI), 0.9-1.8]. The adjusted odds ratio associating with the development of CIN2/3 was 3.0 (95% CI, 1.2-7.4) for persistent infections with HR variants for 6 months and 10.0 (95% CI, 3.8-38.0) for persistent infections with HR variants for 12-18 months as compared with the first positive detection of HR variants. Among women with non-HR variants, there were no appreciable differences in risk of CIN2/3 by length of positivity. Findings suggest that the lineage-associated risk of CIN2/3 was not mediated through a prolonged persistent infection, but oncogenic heterogeneity of the variants.
C1 [Xi, Long Fu; Hulbert, Ayaka; Shen, Zhenping; Kiviat, Nancy B.] Univ Washington, Sch Med, Dept Pathol, NJB Ste 1187,325 9th Ave, Seattle, WA 98104 USA.
[Xi, Long Fu; Koutsky, Laura A.] Univ Washington, Sch Publ Hlth & Community Med, Dept Epidemiol, NJB Ste 1187,325 9th Ave, Seattle, WA 98104 USA.
[Schiffman, Mark] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Hughes, James P.] Univ Washington, Sch Publ Hlth & Community Med, Dept Biostat, NJB Ste 1187,325 9th Ave, Seattle, WA 98104 USA.
[Galloway, Denise A.] Fred Hutchinson Canc Res Ctr, Div Human Biol, 1124 Columbia St, Seattle, WA 98104 USA.
RP Xi, LF (reprint author), Univ Washington, Harborview Med Ctr, Dept Pathol, NJB Ste 1187,325 9th Ave, Seattle, WA 98104 USA.
EM longfu@u.washington.edu
FU National Cancer Institute of the National Institutes of Health
[CA133569]
FX This study was part of the project ancillary to the ALTS clinical trial
but does not represent the views of the ALTS Group. The authors would
like to thank the ALTS Group Investigators for their planning and
conducting the trial and for providing the biological specimens and data
to the present study. We also thank Information Management Services,
Calverton, MD for data management and programming support. The research
reported in this publication was supported by National Cancer Institute
of the National Institutes of Health under award number CA133569. The
content is solely the responsibility of the authors and does not
necessarily represent the official views of the National Institutes of
Health. All authors have no commercial or other associations that might
pose a conflict of interest.
NR 38
TC 0
Z9 0
U1 7
U2 11
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 SEP 1
PY 2016
VL 139
IS 5
BP 1098
EP 1105
DI 10.1002/ijc.30164
PG 8
WC Oncology
SC Oncology
GA DP3TR
UT WOS:000378418800015
PM 27121353
ER
PT J
AU Liow, JS
Zoghbi, SS
Hu, S
Hall, MD
Hines, CS
Shetty, HU
Araneta, MD
Page, EM
Pike, VW
Kreisl, WC
Herscovitch, P
Gottesman, MM
Theodore, WH
Innis, RB
AF Liow, Jeih-San
Zoghbi, Sami S.
Hu, Shuo
Hall, Matthew D.
Hines, Christina S.
Shetty, H. Umesha
Araneta, Maria D.
Page, Emily M.
Pike, Victor W.
Kreisl, William C.
Herscovitch, Peter
Gottesman, Michael M.
Theodore, William H.
Innis, Robert B.
TI F-18-FCWAY, a serotonin 1A receptor radioligand, is a substrate for
efflux transport at the human blood-brain barrier
SO NEUROIMAGE
LA English
DT Article
DE PET; Efflux transporter; P-gp; Blood brain barrier; 5-HT1A
ID TEMPORAL-LOBE EPILEPSY; P-GLYCOPROTEIN; 5-HT1A RECEPTORS; RODENT BRAIN;
PET; DEFLUORINATION; METABOLITES; INHIBITION; WAY-100635; EXPRESSION
AB Efflux transporters at the blood-brain barrier can decrease the entry of drugs and increase the removal of those molecules able to bypass the transporter. We previously hypothesized that F-18-FCWAY, a radioligand for the serotonin 5-HT1A receptor, is a weak substrate for permeability glycoprotein (P-gp) based on its very early peak and rapid washout from human brain. To determine whether F-18-FCWAY is a substrate for P-gp, breast cancer resistance protein (BCRP), and multidrug resistance protein (MRP1) - the three most prevalent efflux transporters at the blood-brain barrier - we performed three sets of experiments. In vitro, we conducted fluorescence-activated cell sorting (FACS) flow cytometry studies in cells over-expressing P-gp, BCRP, and MRP1 treated with inhibitors specific to each transporter and with FCWAY. Ex vivo, we measured F-18-FCWAY concentration in plasma and brain homogenate of transporter knockout mice using gamma-counter and radio-HPLC. In vivo, we conducted positron emission tomography (PET) studies to assess changes in humans who received F-18-FCWAY during an infusion of tariquidar (2-4mg/kg iv), a potent and selective P-gp inhibitor. In vitro studies showed that FCWAY allowed fluorescent substrates to get into the cell by competitive inhibition of all three transporters at the cell membrane. Ex vivo measurements in knockout mice indicate that F-18-FCWAY is a substrate only for P-gp and not BCRP. In vivo, tariquidar increased F-18-FCWAY brain uptake in seven of eight subjects by 60-100% compared to each person's baseline. Tariquidar did not increase brain uptake via some peripheral mechanism, given that it did not significantly alter concentrations in plasma of the parent radioligand F-18-FCWAY or its brain-penetrant radiometabolite F-18-FC. These results show that F-18-FCWAY is a weak substrate for efflux transport at the blood-brain barrier; some radioligand can enter brain, but its removal is hastened by P-gp. Although F-18-FCWAY is not ideal for measuring 5-HT1A receptors, it demonstrates that weak substrate radioligands can be useful for measuring both increased and decreased function of efflux transporters, which is not possible with currently available radioligands such as C-11-loperamide and C-11-verapamil that are avid substrates for transporters. Published by Elsevier Inc.
C1 [Liow, Jeih-San; Zoghbi, Sami S.; Shetty, H. Umesha; Araneta, Maria D.; Page, Emily M.; Pike, Victor W.; Innis, Robert B.] NIMH, Mol Imaging Branch, NIH, 10 Ctr Dr, Bethesda, MD 20892 USA.
[Hu, Shuo] Cent S Univ, Xiang Ya Hosp, PET Ctr, Changsha, Hunan, Peoples R China.
[Hall, Matthew D.] NCATS Chem Genom Ctr, Rockville, MD USA.
[Hines, Christina S.] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX 78229 USA.
[Kreisl, William C.] Columbia Univ, Taub Inst Res Alzheimers Dis & Aging Brain, New York, NY USA.
[Herscovitch, Peter] NIH, PET Dept, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA.
[Gottesman, Michael M.] NCI, Multidrug Resistance Sect, NIH, Bethesda, MD 20892 USA.
[Theodore, William H.] NINDS, Clin Epilepsy Sect, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
RP Liow, JS (reprint author), NIMH, Mol Imaging Branch, NIH, 10 Ctr Dr, Bethesda, MD 20892 USA.
EM liowj@mail.nih.gov
FU Intramural Research Program of the National Institute Mental Health, NIH
[ZIAMH002852, ZIAMH002793, NCT01386476]
FX This study was funded by the Intramural Research Program of the National
Institute Mental Health, NIH: projects ZIAMH002852 and ZIAMH002793,
under clinical protocol NCT01386476. All authors have no conflicts of
interest to disclose.
NR 25
TC 0
Z9 0
U1 6
U2 10
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 SEP
PY 2016
VL 138
BP 134
EP 140
DI 10.1016/j.neuroimage.2016.05.045
PG 7
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA DP5ET
UT WOS:000378519500011
PM 27211474
ER
PT J
AU Huo, Y
Plassard, AJ
Carass, A
Resnick, SM
Pham, DL
Prince, JL
Landman, BA
AF Huo, Yuankai
Plassard, Andrew J.
Carass, Aaron
Resnick, Susan M.
Pham, Dzung L.
Prince, Jerry L.
Landman, Bennett A.
TI Consistent cortical reconstruction and multi-atlas brain segmentation
SO NEUROIMAGE
LA English
DT Article
DE Multi-atlas segmentation; Magnetic resonance imaging; Cerebral cortex;
Cortical reconstruction
ID HUMAN CEREBRAL-CORTEX; MAGNETIC-RESONANCE IMAGES; AUTOMATED 3-D
EXTRACTION; SURFACE-BASED ANALYSIS; TISSUE CLASSIFICATION; COORDINATE
SYSTEM; OLDER-ADULTS; LABEL FUSION; MR-IMAGES; THICKNESS
AB Whole brain segmentation and cortical surface reconstruction are two essential techniques for investigating the human brain. Spatial inconsistences, which can hinder further integrated analyses of brain structure, can result due to these two tasks typically being conducted independently of each other. FreeSurfer obtains selfconsistent whole brain segmentations and cortical surfaces. It starts with subcortical segmentation, then carries out cortical surface reconstruction, and ends with cortical segmentation and labeling. However, this "segmentation to surface to parcellation" strategy has shown limitations in various cohorts such as older populations with large ventricles. In this work, we propose a novel "multi-atlas segmentation to surface" method calledMulti-atlas CRUISE (MaCRUISE), which achieves self-consistent whole brain segmentations and cortical surfaces by combining multi-atlas segmentation with the cortical reconstruction method CRUISE. A modification called MaCRUISE(+) is designed to perform well when white matter lesions are present. Comparing to the benchmarks CRUISE and FreeSurfer, the surface accuracy of MaCRUISE and MaCRUISE+ is validated using two independent datasets with expertly placed cortical landmarks. A third independent dataset with expertly delineated volumetric labels is employed to compare segmentation performance. Finally, 200MR volumetric images from an older adult sample are used to assess the robustness of MaCRUISE and FreeSurfer. The advantages of MaCRUISE are: (1) MaCRUISE constructs self-consistent voxelwise segmentations and cortical surfaces, while MaCRUISE(+) is robust to white matter pathology. (2) MaCRUISE achieves more accurate whole brain segmentations than independently conducting the multi-atlas segmentation. (3) MaCRUISE is comparable in accuracy to FreeSurfer (when FreeSurfer does not exhibit global failures) while achieving greater robustness across an older adult population. MaCRUISE has been made freely available in open source. (C) 2016 Elsevier Inc. All rights reserved.
C1 [Huo, Yuankai; Landman, Bennett A.] Vanderbilt Univ, Elect Engn, EECS 2301,Vanderbilt Pl,POB 351679 Stn B, Nashville, TN 37235 USA.
[Plassard, Andrew J.; Landman, Bennett A.] Vanderbilt Univ, Comp Sci, EECS 2301,Vanderbilt Pl,POB 351679 Stn B, Nashville, TN 37235 USA.
[Carass, Aaron; Prince, Jerry L.] Johns Hopkins Univ, Image Anal & Commun Lab, Baltimore, MD USA.
[Resnick, Susan M.] Natl Inst Aging, Lab Behav Neurosci, Baltimore, MD USA.
[Pham, Dzung L.] Henry Jackson Fdn, Ctr Neurosci & Regenerat Med, Bethesda, MD USA.
[Landman, Bennett A.] Vanderbilt Univ, Inst Imaging Sci, EECS 2301,Vanderbilt Pl,POB 351679 Stn B, Nashville, TN 37235 USA.
[Landman, Bennett A.] Vanderbilt Univ, Radiol & Radiol Sci, EECS 2301,Vanderbilt Pl,POB 351679 Stn B, Nashville, TN 37235 USA.
RP Huo, Y (reprint author), Vanderbilt Univ, EECS 2301,Vanderbilt Pl,POB 351679 Stn B, Nashville, TN 37235 USA.
EM yuankai.huo@vanderbilt.edu
OI Huo, Yuankai/0000-0002-2096-8065; Carass, Aaron/0000-0003-4939-5085
FU NSF CAREER [1452485]; NIH [5R21EY024036, 1R21NS064534, 1R01NS070906,
5R01NS056307, 1R21NS096497, 2R01EB006136, 1R03EB012461, R01EB006193,
5R21NS082891]; Intramural Research Program, National Institute on Aging,
NIH; National MS Society [RG-1507-05243]; Advanced Computing Center for
Research and Education (ACCRE) at Vanderbilt University, Nashville, TN;
ViSE/VICTR [VR3029]; National Center for Research Resources [UL1
RR024975-01]; National Center for Advancing Translational Sciences [2
UL1 TR000445-06]; Department of Defense in the Center for Neuroscience
and Regenerative Medicine
FX This research was supported by NSF CAREER 1452485 (Landman), NIH grants
5R21EY024036 (Landman), 1R21NS064534 (Prince/Landman), 1R01NS070906
(Pham), 5R01NS056307 (Prince), 1R21NS096497 (Prince), 2R01EB006136
(Dawant), 1R03EB012461 (Landman) and R01EB006193 (Dawant). This research
was conducted with the support from Intramural Research Program,
National Institute on Aging, NIH. This research was supported by
National MS Society RG-1507-05243 (Pham). This study was also supported
by NIH 5R01NS056307, 5R21NS082891 and in part using the resources of the
Advanced Computing Center for Research and Education (ACCRE) at
Vanderbilt University, Nashville, TN. This project was supported in part
by ViSE/VICTR VR3029 and the National Center for Research Resources,
Grant UL1 RR024975-01, and is now at the National Center for Advancing
Translational Sciences, Grant 2 UL1 TR000445-06. Support for this work
included funding from the Department of Defense in the Center for
Neuroscience and Regenerative Medicine. The authors are responsible for
the content. The content does not necessarily represent the official
views of the NIH. We are grateful for the assistance of Naresh
Nandakumar in helping prepare this manuscript.
NR 92
TC 1
Z9 1
U1 6
U2 10
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 SEP
PY 2016
VL 138
BP 197
EP 210
DI 10.1016/j.neuroimage.2016.05.030
PG 14
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA DP5ET
UT WOS:000378519500017
PM 27184203
ER
PT J
AU Guo, AL
Xu, YF
Mowery, J
Nagy, A
Bauchan, G
Nou, XW
AF Guo, Ailing
Xu, Yunfeng
Mowery, Joseph
Nagy, Attila
Bauchan, Gary
Nou, Xiangwu
TI Ralstonia insidiosa induces cell aggregation of Listeria monocytogenes
SO FOOD CONTROL
LA English
DT Article
DE Listeria monocytogenes; Ralstonia insidiosa; Cell aggregation; Biofilms;
TEM
ID ESCHERICHIA-COLI O157H7; BIOFILM FORMATION; STRAINS; COAGGREGATION;
PREVALENCE; CANTALOUPE; PICKETTII; OUTBREAK; GROWTH; LEVEL
AB Biofilm formation is an important strategy for foodborne bacterial pathogens to survive in stressful environments such as fresh produce processing facilities. Bacterial cell aggregation strongly promotes the initiation of microcolonies and the formation of biofilms on abiological surfaces. We previously showed that Ralstonia insidiosa, an environmental bacterial species frequently isolated from fresh produce facilities, may serve as a "bridge bacterium" that strongly enhanced the incorporation of several foodborne bacterial pathogens into dual species biofilms. While the R. insidiosa strain exhibited moderate cell aggregation in liquid culture, co-culturing Listeria monocytogenes with R. insidiosa resulted in significant augmentation of cell aggregation. Electron microscopy indicated that L. monocytogenes cells were initially attracted to the R. insidiosa aggregates and formed large dual species aggregates that were predominately composed of L. monocytogenes cells. The predominant presence of L. monocytogenes in the dual species aggregates was also confirmed by differential plating. These findings suggest that bridge bacteria such as R. insidiosa play critical roles in the survival of foodborne bacterial pathogens, such as L. monocytogenes and Escherichia coli, by promoting multispecies biofilm formation. The implications of such bridge bacteria on food safety need to be further evaluated. Published by Elsevier Ltd.
C1 [Guo, Ailing] Huazhong Agr Univ, Natl Res & Dev Ctr Egg Proc, Wuhan 430070, Peoples R China.
[Xu, Yunfeng; Nagy, Attila; Nou, Xiangwu] ARS, Environm Microbial & Food Safety Lab, Beltsville Agr Res Ctr, USDA, Beltsville, MD 20705 USA.
[Mowery, Joseph; Bauchan, Gary] ARS, Electron & Confocal Microscopy Unit, Beltsville Agr Res Ctr, USDA, Beltsville, MD 20705 USA.
[Nagy, Attila] NIAID, NIH, Vaccine Res Ctr, Gaithersburg, MD 20878 USA.
RP Nou, XW (reprint author), ARS, Environm Microbial & Food Safety Lab, Beltsville Agr Res Ctr, USDA, Beltsville, MD 20705 USA.
EM Xiangwu.nou@ars.usda.gov
FU Huazhong Agricultural University; China Scholarship Council
FX Authors wish to thank Dr. T. Ward for providing L.monocytogenes strains
used in this study. Ailing Guo was a visiting scientist to USDA ARS
EMFSL from and supported by Huazhong Agricultural University, and
Yunfeng Xu is predoctoral student from Northwest A&F University, China,
and is supported by China Scholarship Council.
NR 37
TC 0
Z9 0
U1 6
U2 16
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0956-7135
EI 1873-7129
J9 FOOD CONTROL
JI Food Control
PD SEP
PY 2016
VL 67
BP 303
EP 309
DI 10.1016/j.foodcont.2016.03.006
PG 7
WC Food Science & Technology
SC Food Science & Technology
GA DK8FY
UT WOS:000375163800039
ER
PT J
AU Wang, YC
Chin, KH
Tu, ZL
He, J
Jones, CJ
Sanchez, DZ
Yildiz, FH
Galperin, MY
Chou, SH
AF Wang, Yu-Chuan
Chin, Ko-Hsin
Tu, Zhi-Le
He, Jin
Jones, Christopher J.
Sanchez, David Zamorano
Yildiz, Fitnat H.
Galperin, Michael Y.
Chou, Shan-Ho
TI Nucleotide binding by the widespread high-affinity cyclic di-GMP
receptor MshEN domain
SO NATURE COMMUNICATIONS
LA English
DT Article
ID II SECRETION SYSTEM; MOLECULAR DISCRIMINATION; MECHANISTIC INSIGHTS;
STRUCTURAL BASIS; YDAO RIBOSWITCH; PILZ-DOMAIN; PROTEIN; DATABASE; AMP;
2ND-MESSENGER
AB C-di-GMP is a bacterial second messenger regulating various cellular functions. Many bacteria contain c-di-GMP-metabolizing enzymes but lack known c-di-GMP receptors. Recently, two MshE-type ATPases associated with bacterial type II secretion system and type IV pilus formation were shown to specifically bind c-di-GMP. Here we report crystal structure of the MshE N-terminal domain (MshEN(1-145)) from Vibrio cholerae in complex with c-di-GMP at a 1.37 resolution. This structure reveals a unique c-di-GMP-binding mode, featuring a tandem array of two highly conserved binding motifs, each comprising a 24-residue sequence RLGxx(L/V/I)(L/V/I)xxG(L/V/I)(L/V/I)xxxxLxxxLxxQ that binds half of the c-di-GMP molecule, primarily through hydrophobic interactions. Mutating these highly conserved residues markedly reduces c-di-GMP binding and biofilm formation by V. cholerae. This c-di-GMP-binding motif is present in diverse bacterial proteins exhibiting binding affinities ranging from 0.5 mu M to as low as 14 nM. The MshEN domain contains the longest nucleotide-binding motif reported to date.
C1 [Wang, Yu-Chuan; Tu, Zhi-Le; Chou, Shan-Ho] Natl Chung Hsing Univ, Inst Biochem, Taichung 40227, Taiwan.
[Chin, Ko-Hsin; Chou, Shan-Ho] Natl Chung Hsing Univ, Agr Biotechnol Ctr, Taichung 40227, Taiwan.
[He, Jin] Huazhong Agr Univ, Coll Life Sci & Technol, State Key Lab Agr Microbiol, Wuhan 430070, Hubei, Peoples R China.
[Jones, Christopher J.; Sanchez, David Zamorano; Yildiz, Fitnat H.] Univ Calif Santa Cruz, Dept Microbiol & Environm Toxicol, Santa Cruz, CA 95064 USA.
[Galperin, Michael Y.] Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA.
RP Chou, SH (reprint author), Natl Chung Hsing Univ, Inst Biochem, Taichung 40227, Taiwan.; Chou, SH (reprint author), Natl Chung Hsing Univ, Agr Biotechnol Ctr, Taichung 40227, Taiwan.
EM shchou@nchu.edu.tw
OI Galperin, Michael/0000-0002-2265-5572
FU Ministry of Education, Taiwan, ROC under the ATU plan; Ministry of
Science and Technology, Taiwan, ROC [102-2113-M-005 -006 -MY3]; NIH [RO1
AI102584]; NIH Intramural Research Program at the US National Library of
Medicine
FX This work was supported in part by the Ministry of Education, Taiwan,
ROC under the ATU plan, and by the Ministry of Science and Technology,
Taiwan, ROC (102-2113-M-005 -006 -MY3) to S.-H.C. and NIH award RO1
AI102584 to F.H.Y. M.Y.G. was supported by the NIH Intramural Research
Program at the US National Library of Medicine. We would also like to
thank the National Synchrotron Radiation Research Center (NSRRC) in
Taiwan, and the SPring-8 Synchrotron facility in Japan for assistance of
the X-ray data collections.
NR 51
TC 2
Z9 2
U1 4
U2 4
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 AUG 31
PY 2016
VL 7
AR 12481
DI 10.1038/ncomms12481
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EH6FY
UT WOS:000391869500001
PM 27578558
ER
PT J
AU Wen, PJ
Grenklo, S
Arpino, G
Tan, XY
Liao, HS
Heureaux, J
Peng, SY
Chiang, HC
Hamid, E
Zhao, WD
Shin, W
Nareoja, T
Evergren, E
Jin, YH
Karlsson, R
Ebert, SN
Jin, A
Liu, AP
Shupliakov, O
Wu, LG
AF Wen, Peter J.
Grenklo, Staffan
Arpino, Gianvito
Tan, Xinyu
Liao, Hsien-Shun
Heureaux, Johanna
Peng, Shi-Yong
Chiang, Hsueh-Cheng
Hamid, Edaeni
Zhao, Wei-Dong
Shin, Wonchul
Naereoja, Tuomas
Evergren, Emma
Jin, Yinghui
Karlsson, Roger
Ebert, Steven N.
Jin, Albert
Liu, Allen P.
Shupliakov, Oleg
Wu, Ling-Gang
TI Actin dynamics provides membrane tension to merge fusing vesicles into
the plasma membrane
SO NATURE COMMUNICATIONS
LA English
DT Article
ID ADRENAL CHROMAFFIN CELLS; KISS-AND-RUN; CROSS-LINKED PROFILIN;
DENSE-CORE VESICLES; REGULATED EXOCYTOSIS; F-ACTIN; COMPENSATORY
ENDOCYTOSIS; NEUROENDOCRINE CELLS; STRUCTURAL-CHANGES; SYNAPTIC VESICLES
AB Vesicle fusion is executed via formation of an Omega-shaped structure (Omega-profile), followed by closure (kiss-and-run) or merging of the Omega-profile into the plasma membrane (full fusion). Although Omega-profile closure limits release but recycles vesicles economically, Omega-profile merging facilitates release but couples to classical endocytosis for recycling. Despite its crucial role in determining exocytosis/endocytosis modes, how Omega-profile merging is mediated is poorly understood in endocrine cells and neurons containing small similar to 30-300 nm vesicles. Here, using confocal and super-resolution STED imaging, force measurements, pharmacology and gene knockout, we show that dynamic assembly of filamentous actin, involving ATP hydrolysis, N-WASP and formin, mediates Omega-profile merging by providing sufficient plasma membrane tension to shrink the Omega-profile in neuroendocrine chromaffin cells containing similar to 300 nm vesicles. Actin-directed compounds also induce Omega-profile accumulation at lamprey synaptic active zones, suggesting that actin may mediate Omega-profile merging at synapses. These results uncover molecular and biophysical mechanisms underlying Omega-profile merging.
C1 [Wen, Peter J.; Arpino, Gianvito; Peng, Shi-Yong; Chiang, Hsueh-Cheng; Hamid, Edaeni; Zhao, Wei-Dong; Shin, Wonchul; Jin, Yinghui; Wu, Ling-Gang] Natl Inst Neurol Disorders & Stroke, 35 Convent Dr,Bldg 35,Room 2B 1012, Bethesda, MD 20892 USA.
[Grenklo, Staffan; Arpino, Gianvito; Naereoja, Tuomas; Evergren, Emma; Shupliakov, Oleg] Karolinska Inst, Ctr Excellence Dev Biol, Dept Neurosci, S-17177 Stockholm, Sweden.
[Grenklo, Staffan; Karlsson, Roger] Stockholm Univ, WGI, Dept Cell Biol, S-10691 Stockholm, Sweden.
[Tan, Xinyu; Heureaux, Johanna; Liu, Allen P.] Univ Michigan, Dept Mech Engn, Ann Arbor, MI 48109 USA.
[Liao, Hsien-Shun; Jin, Albert] NIBIB, Bethesda, MD 20892 USA.
[Ebert, Steven N.] Univ Cent Florida, Burnett Sch Biomed Sci, Coll Med, 6900 Lake Nona Blvd, Orlando, FL 32827 USA.
[Shupliakov, Oleg] St Petersburg State Univ, Inst Translat Biomed, St Petersburg 199034, Russia.
[Chiang, Hsueh-Cheng] Natl Cheng Kung Univ, Coll Med, Dept Pharmacol, 1 Univ Rd, Tainan 701, Taiwan.
[Evergren, Emma] Queens Univ Belfast, Ctr Canc Res & Cell Biol, Belfast BT9 7AE, Antrim, North Ireland.
RP Wu, LG (reprint author), Natl Inst Neurol Disorders & Stroke, 35 Convent Dr,Bldg 35,Room 2B 1012, Bethesda, MD 20892 USA.; Shupliakov, O (reprint author), Karolinska Inst, Ctr Excellence Dev Biol, Dept Neurosci, S-17177 Stockholm, Sweden.; Shupliakov, O (reprint author), St Petersburg State Univ, Inst Translat Biomed, St Petersburg 199034, Russia.
EM oleg.shupliakov@ki.se; wul@ninds.nih.gov
RI Nareoja, Tuomas/K-3800-2014
OI Nareoja, Tuomas/0000-0002-2174-4434
FU National Institute of Neurological Disorders and Stroke Intramural
Research Program [ZIA NS003009-13, ZIA NS003105-08]; Swedish Research
Council [13473]; Parkinsonfonden; Hjarnfonden; Russian Science
Foundation [16-15-10273]
FX We thank Dr James Ervasti for providing Actbloxp mice. This work was
supported by the National Institute of Neurological Disorders and Stroke
Intramural Research Program (ZIA NS003009-13 and ZIA NS003105-08) to
L.G.W. and by grants from the Swedish Research Council (project 13473),
Parkinsonfonden, Hjarnfonden and the Russian Science Foundation (project
number 16-15-10273) to O.S.
NR 67
TC 2
Z9 2
U1 6
U2 6
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 AUG 31
PY 2016
VL 7
AR 12604
DI 10.1038/ncomms12604
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EH6GO
UT WOS:000391871100001
PM 27576662
ER
PT J
AU Zaslavsky, L
Ciufo, S
Fedorov, B
Tatusova, T
AF Zaslavsky, Leonid
Ciufo, Stacy
Fedorov, Boris
Tatusova, Tatiana
TI Clustering analysis of proteins from microbial genomes at multiple
levels of resolution
SO BMC BIOINFORMATICS
LA English
DT Article; Proceedings Paper
CT 11th International Symposium on Bioinformatics Research and Applications
(ISBRA)
CY JUN 07-10, 2015
CL Old Domin Univ, Norfolk, VA
HO Old Domin Univ
DE Protein; Cluster; Clustering; Microbial; Procaryotic; Core-periphery;
Multiscale; Multiresolution; Knowledge discovery; Data mining; Parallel
processing; Parallel computing
ID BACTERIAL PAN-GENOME; PARALLEL ALGORITHMS; SEARCH; ORTHOLOGS; ALIGNMENT;
BLAST
AB Background: Microbial genomes at the National Center for Biotechnology Information (NCBI) represent a large collection of more than 35,000 assemblies. There are several complexities associated with the data: a great variation in sampling density since human pathogens are densely sampled while other bacteria are less represented; different protein families occur in annotations with different frequencies; and the quality of genome annotation varies greatly. In order to extract useful information from these sophisticated data, the analysis needs to be performed at multiple levels of phylogenomic resolution and protein similarity, with an adequate sampling strategy.
Results: Protein clustering is used to construct meaningful and stable groups of similar proteins to be used for analysis and functional annotation. Our approach is to create protein clusters at three levels. First, tight clusters in groups of closely-related genomes (species-level clades) are constructed using a combined approach that takes into account both sequence similarity and genome context. Second, clustroids of conservative in-clade clusters are organized into seed global clusters. Finally, global protein clusters are built around the the seed clusters. We propose filtering strategies that allow limiting the protein set included in global clustering. The in-clade clustering procedure, subsequent selection of clustroids and organization into seed global clusters provides a robust representation and high rate of compression. Seed protein clusters are further extended by adding related proteins. Extended seed clusters include a significant part of the data and represent all major known cell machinery. The remaining part, coming from either non-conservative (unique) or rapidly evolving proteins, from rare genomes, or resulting from low-quality annotation, does not group together well. Processing these proteins requires significant computational resources and results in a large number of questionable clusters.
Conclusion: The developed filtering strategies allow to identify and exclude such peripheral proteins limiting the protein dataset in global clustering. Overall, the proposed methodology allows the relevant data at different levels of details to be obtained and data redundancy eliminated while keeping biologically interesting variations.
C1 [Zaslavsky, Leonid; Ciufo, Stacy; Fedorov, Boris; Tatusova, Tatiana] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
RP Zaslavsky, L (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
EM zaslavsk@ncbi.nlm.nih.gov
NR 43
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 1471-2105
J9 BMC BIOINFORMATICS
JI BMC Bioinformatics
PD AUG 31
PY 2016
VL 17
SU 8
AR 276
DI 10.1186/s12859-016-1112-8
PG 8
WC Biochemical Research Methods; Biotechnology & Applied Microbiology;
Mathematical & Computational Biology
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Mathematical & Computational Biology
GA DW5AV
UT WOS:000383655300001
PM 27586436
ER
PT J
AU Kim, DA
Benjamin, EJ
Fowler, JH
Christakis, NA
AF Kim, David A.
Benjamin, Emelia J.
Fowler, James H.
Christakis, Nicholas A.
TI Social connectedness is associated with fibrinogen level in a human
social network
SO PROCEEDINGS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES
LA English
DT Article
DE social networks; social epidemiology; fibrinogen; social hierarchy;
stress response
ID CORONARY-HEART-DISEASE; MORTALITY; HEALTH; DETERMINANTS; SPREAD;
LONELINESS; INEQUALITY; FRIENDSHIP; DYNAMICS; WOMEN
AB Socially isolated individuals face elevated rates of illness and death. Conventional measures of social connectedness reflect an individual's perceived network and can be subject to bias and variation in reporting. In this study of a large human social network, we find that greater indegree, a sociocentric measure of friendship and familial ties identified by a subject's social connections rather than by the subject, predicts significantly lower concentrations of fibrinogen (a biomarker of inflammation and cardiac risk), after adjusting for demographics, education, medical history and known predictors of cardiac risk. The association between fibrinogen and social isolation, as measured by low indegree, is comparable to the effect of smoking, and greater than that of low education, a conventional measure of socioeconomic disadvantage. By contrast, outdegree, which reflects an individual's perceived connectedness, displays a significantly weaker association with fibrinogen concentrations.
C1 [Kim, David A.] Stanford Univ, Dept Emergency Med, 300 Pasteur Dr MC 5119, Stanford, CA 94305 USA.
[Benjamin, Emelia J.] Natl Heart Lung & Blood Inst, 73 Mt Wayte Ave, Framingham, MA 01702 USA.
[Benjamin, Emelia J.] Boston Univ, Framingham Heart Study, 73 Mt Wayte Ave, Framingham, MA 01702 USA.
[Fowler, James H.] Univ Calif San Diego, Dept Med, 9500 Gilman Dr 0521, La Jolla, CA 92093 USA.
[Fowler, James H.] Univ Calif San Diego, Dept Polit Sci, 9500 Gilman Dr 0521, La Jolla, CA 92093 USA.
[Christakis, Nicholas A.] Yale Univ, Dept Med, POB 208263, New Haven, CT 06520 USA.
[Christakis, Nicholas A.] Yale Univ, Dept Ecol & Evolutionary Biol, POB 208263, New Haven, CT 06520 USA.
[Christakis, Nicholas A.] Yale Univ, Dept Sociol, POB 208263, New Haven, CT 06520 USA.
RP Christakis, NA (reprint author), Yale Univ, Dept Med, POB 208263, New Haven, CT 06520 USA.; Christakis, NA (reprint author), Yale Univ, Dept Ecol & Evolutionary Biol, POB 208263, New Haven, CT 06520 USA.; Christakis, NA (reprint author), Yale Univ, Dept Sociol, POB 208263, New Haven, CT 06520 USA.
EM nicholas.christakis@yale.edu
OI Kim, David/0000-0003-0151-5121
FU NIH [P01AG31093]; National Institute on Aging; Canadian Institutes of
Health Research; [HHSN268201500001I]; [N01-HC 25195]
FX This work was supported by NIH grant no. P01AG31093 and by the National
Institute on Aging. D.A.K. was supported by the Canadian Institutes of
Health Research. The FHS is supported by HHSN268201500001I and N01-HC
25195.
NR 48
TC 0
Z9 0
U1 5
U2 5
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 AUG 31
PY 2016
VL 283
IS 1837
AR 20160958
DI 10.1098/rspb.2016.0958
PG 7
WC Biology; Ecology; Evolutionary Biology
SC Life Sciences & Biomedicine - Other Topics; Environmental Sciences &
Ecology; Evolutionary Biology
GA DY4FY
UT WOS:000385055600018
ER
PT J
AU Pugacheva, EM
Teplyakov, E
Wu, QF
Li, JJ
Chen, C
Meng, CC
Liu, J
Robinson, S
Loukinov, D
Boukaba, A
Hutchins, AP
Lobanenkov, V
Strunnikov, A
AF Pugacheva, Elena M.
Teplyakov, Evgeny
Wu, Qiongfang
Li, Jingjing
Chen, Cheng
Meng, Chengcheng
Liu, Jian
Robinson, Susan
Loukinov, Dmitry
Boukaba, Abdelhalim
Hutchins, Andrew Paul
Lobanenkov, Victor
Strunnikov, Alexander
TI The cancer-associated CTCFL/BORIS protein targets multiple classes of
genomic repeats, with a distinct binding and functional preference for
humanoid-specific SVA transposable elements
SO EPIGENETICS & CHROMATIN
LA English
DT Article
ID DNA METHYLATION; CTCF BINDING; SOMATIC RETROTRANSPOSITION; ENDOGENOUS
RETROVIRUSES; EXPANSION DISORDERS; PLURIPOTENT CELLS; GENE PROMOTERS;
FACTOR BORIS; STEM-CELLS; EXPRESSION
AB Background: A common aberration in cancer is the activation of germline-specific proteins. The DNA-binding proteins among them could generate novel chromatin states, not found in normal cells. The germline-specific transcription factor BORIS/CTCFL, a paralog of chromatin architecture protein CTCF, is often erroneously activated in cancers and rewires the epigenome for the germline-like transcription program. Another common feature of malignancies is the changed expression and epigenetic states of genomic repeats, which could alter the transcription of neighboring genes and cause somatic mutations upon transposition. The role of BORIS in transposable elements and other repeats has never been assessed.
Results: The investigation of BORIS and CTCF binding to DNA repeats in the K562 cancer cells dependent on BORIS for self-renewal by ChIP-chip and ChIP-seq revealed three classes of occupancy by these proteins: elements cohabited by BORIS and CTCF, CTCF-only bound, or BORIS-only bound. The CTCF-only enrichment is characteristic for evolutionary old and inactive repeat classes, while BORIS and CTCF co-binding predominately occurs at uncharacterized tandem repeats. These repeats form staggered cluster binding sites, which are a prerequisite for CTCF and BORIS co-binding. At the same time, BORIS preferentially occupies a specific subset of the evolutionary young, transcribed, and mobile genomic repeat family, SVA. Unlike CTCF, BORIS prominently binds to the VNTR region of the SVA repeats in vivo. This suggests a role of BORIS in SVA expression regulation. RNA-seq analysis indicates that BORIS largely serves as a repressor of SVA expression, alongside DNA and histone methylation, with the exception of promoter capture by SVA.
Conclusions: Thus, BORIS directly binds to, and regulates SVA repeats, which are essentially movable CpG islands, via clusters of BORIS binding sites. This finding uncovers a new function of the global germline-specific transcriptional regulator BORIS in regulating and repressing the newest class of transposable elements that are actively transposed in human genome when activated. This function of BORIS in cancer cells is likely a reflection of its roles in the germline.
C1 [Teplyakov, Evgeny; Wu, Qiongfang; Li, Jingjing; Chen, Cheng; Meng, Chengcheng; Liu, Jian; Boukaba, Abdelhalim; Strunnikov, Alexander] Guangzhou Inst Biomed & Hlth, Mol Epigenet Lab, Guangzhou 510530, Guangdong, Peoples R China.
[Pugacheva, Elena M.; Robinson, Susan; Loukinov, Dmitry; Lobanenkov, Victor] NIAID, Lab Immunogenet, NIH, Rockville, MD 20852 USA.
[Hutchins, Andrew Paul] Southern Univ Sci & Technol China, Dept Biol, Shenzhen 518055, Guangdong, Peoples R China.
RP Strunnikov, A (reprint author), Guangzhou Inst Biomed & Hlth, Mol Epigenet Lab, Guangzhou 510530, Guangdong, Peoples R China.
EM alex@gibh.org
FU PRC government's "1000 Talents Program" grant; Guangdong provincial
government's "Guangdong High Talent" award; Intramural Program of the
National Institute of Allergy and Infectious Diseases
FX This work was supported by the PRC government's "1000 Talents Program"
grant to AS, the Guangdong provincial government's "Guangdong High
Talent" award to AS, and the Intramural Program of the National
Institute of Allergy and Infectious Diseases for VL.
NR 117
TC 1
Z9 1
U1 10
U2 10
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1756-8935
J9 EPIGENET CHROMATIN
JI Epigenetics Chromatin
PD AUG 31
PY 2016
VL 9
AR 35
DI 10.1186/s13072-016-0084-2
PG 20
WC Genetics & Heredity
SC Genetics & Heredity
GA DV8CR
UT WOS:000383165600001
PM 27588042
ER
PT J
AU Yu, LD
Ham, K
Gao, XH
Castro, L
Yan, YT
Kissling, GE
Tucker, CJ
Flagler, N
Dong, R
Archer, TK
Dixon, D
AF Yu, Linda
Ham, Kyle
Gao, Xiaohua
Castro, Lysandra
Yan, Yitang
Kissling, Grace E.
Tucker, Charles J.
Flagler, Norris
Dong, Ray
Archer, Trevor K.
Dixon, Darlene
TI Epigenetic regulation of transcription factor promoter regions by
low-dose genistein through mitogen-activated protein kinase and
mitogen-and-stress activated kinase 1 nongenomic signaling
SO CELL COMMUNICATION AND SIGNALING
LA English
DT Article
DE Epigenetic; Histone H3; Leiomyoma; MAPK(p44/42); MSK1
ID HISTONE H3 PHOSPHORYLATION; ESTROGEN-RECEPTOR-ALPHA; BREAST-CANCER
CELLS; HUMAN UTERINE LEIOMYOMAS; MATCHED MYOMETRIUM; GROWTH-FACTORS;
ER-ALPHA; PATHWAY; CHROMATIN; TRANSDUCTION
AB Background: The phytoestrogen, genistein at low doses nongenomically activates mitogen-activated protein kinase p44/42 (MAPK(p44/42)) via estrogen receptor alpha (ER alpha) leading to proliferation of human uterine leiomyoma cells. In this study, we evaluated if MAPK(p44/42) could activate downstream effectors such as mitogen-and stress-activated protein kinase 1 (MSK1), which could then epigenetically modify histone H3 by phosphorylation following a low dose (1 mu g/ml) of genistein.
Results: Using hormone-responsive immortalized human uterine leiomyoma (ht-UtLM) cells, we found that genistein activated MAPK(p44/42) and MSK1, and also increased phosphorylation of histone H3 at serine10 (H3S10ph) in ht-UtLM cells. Colocalization of phosphorylated MSK1 and H3S10ph was evident by confocal microscopy in ht-UtLM cells (r = 0.8533). Phosphorylation of both MSK1 and H3S10ph was abrogated by PD98059 (PD), a MEK1 kinase inhibitor, thereby supporting genistein's activation of MSK1 and Histone H3 was downstream of MAPK(p44/42). In proliferative (estrogenic) phase human uterine fibroid tissues, phosphorylated MSK1 and H3S10ph showed increased immunoexpression compared to normal myometrial tissues, similar to results observed in in vitro studies following low-dose genistein administration. Real-time RT-PCR arrays showed induction of growth-related transcription factor genes, EGR1, Elk1, ID1, and MYB (cMyb) with confirmation by western blot, downstream of MAPK in response to low-dose genistein in ht-UtLM cells. Additionally, genistein induced associations of promoter regions of the above transcription factors with H3S10ph as evidenced by Chromatin Immunoprecipitation (ChIP) assays, which were inhibited by PD. Therefore, genistein epigenetically modified histone H3 by phosphorylation of serine 10, which was regulated by MSK1 and MAPK activation.
Conclusion: Histone H3 phosphorylation possibly represents a mechanism whereby increased transcriptional activation occurs following low-dose genistein exposure.
C1 [Yu, Linda; Ham, Kyle; Gao, Xiaohua; Castro, Lysandra; Yan, Yitang; Dong, Ray; Dixon, Darlene] NIEHS, Mol Pathogenesis Grp, Toxicol Program NTP Lab, Div NTP DNTP,NIH,US Dept Hlth & Human Serv HHS, POB 12233, Res Triangle Pk, NC 27709 USA.
[Kissling, Grace E.] NIEHS, Biostat & Computat Biol Branch, DIR, NIH,HHS, POB 12233, Res Triangle Pk, NC 27709 USA.
[Tucker, Charles J.] NIEHS, Signal Transduct Lab, DIR, NIH,HHS, POB 12233, Res Triangle Pk, NC 27709 USA.
[Flagler, Norris] NIEHS, Cellular & Mol Pathol Branch, DNTP, NIH,HHS, POB 12233, Res Triangle Pk, NC 27709 USA.
[Archer, Trevor K.] NIEHS, Chromatin & Gene Express Grp, Epigenet & Stem Cell Biol Lab, DIR,NIH,HHS, POB 12233, Res Triangle Pk, NC 27709 USA.
RP Dixon, D (reprint author), NIEHS, Mol Pathogenesis Grp, Toxicol Program NTP Lab, Div NTP DNTP,NIH,US Dept Hlth & Human Serv HHS, POB 12233, Res Triangle Pk, NC 27709 USA.
EM dixon@niehs.nih.gov
FU Intramural Research Program of the NIH; NIEHS; DNTP
FX The authors kindly thank Drs. Wei Qu and Kyathanahalli Janardhan for
their critical review of this manuscript. The authors would also like to
thank Alicia B. Moore for her excellent assistance with formatting the
manuscript. This research was supported by the Intramural Research
Program of the NIH, NIEHS and DNTP.
NR 44
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 1478-811X
J9 CELL COMMUN SIGNAL
JI Cell Commun. Signal.
PD AUG 31
PY 2016
VL 14
AR 18
DI 10.1186/s12964-016-0141-2
PG 13
WC Cell Biology
SC Cell Biology
GA DV3IV
UT WOS:000382815400001
PM 27582276
ER
PT J
AU Segade, F
Cota, C
Famiglietti, A
Cha, A
Davidson, B
AF Segade, Fernando
Cota, Christina
Famiglietti, Amber
Cha, Anna
Davidson, Brad
TI Fibronectin contributes to notochord intercalation in the invertebrate
chordate, Ciona intestinalis
SO EVODEVO
LA English
DT Article
DE Chordate evolution; Tunicates; Extracellular matrix; Fibronectin;
Notochord; Convergent extension
ID GENE REGULATORY NETWORK; CONVERGENT EXTENSION; TRANSCRIPTION FACTORS;
EXTRACELLULAR-MATRIX; FUNCTIONAL GENOMICS; ASCIDIAN NOTOCHORD; TISSUE
MECHANICS; CELL MOTILITY; EVOLUTION; HEART
AB Background: Genomic analysis has upended chordate phylogeny, placing the tunicates as the sister group to the vertebrates. This taxonomic rearrangement raises questions about the emergence of a tunicate/vertebrate ancestor.
Results: Characterization of developmental genes uniquely shared by tunicates and vertebrates is one promising approach for deciphering developmental shifts underlying acquisition of novel, ancestral traits. The matrix glycoprotein Fibronectin (FN) has long been considered a vertebrate-specific gene, playing a major instructive role in vertebrate embryonic development. However, the recent computational prediction of an orthologous "vertebrate-like" Fn gene in the genome of a tunicate, Ciona savignyi, challenges this viewpoint suggesting that Fn may have arisen in the shared tunicate/vertebrate ancestor. Here we verify the presence of a tunicate Fn ortholog. Transgenic reporter analysis was used to characterize a Ciona Fn enhancer driving expression in the notochord. Targeted knockdown in the notochord lineage indicates that FN is required for proper convergent extension.
Conclusions: These findings suggest that acquisition of Fn was associated with altered notochord morphogenesis in the vertebrate/tunicate ancestor.
C1 [Segade, Fernando] Univ Penn, Sch Dent Med, Dept Anat & Cell Biol, Philadelphia, PA 19104 USA.
[Cota, Christina; Davidson, Brad] Swarthmore Coll, Dept Biol, 500 Coll Ave, Swarthmore, PA 19081 USA.
[Famiglietti, Amber] Natl Inst Dent & Craniofacial Res, Sect Biol Chem, NIH, Bethesda, MD 20892 USA.
[Cha, Anna] Harvard Med Sch, Dept Syst Biol, Boston, MA USA.
RP Davidson, B (reprint author), Swarthmore Coll, Dept Biol, 500 Coll Ave, Swarthmore, PA 19081 USA.
EM bdavids1@swarthmore.edu
OI Cota, Christina/0000-0003-1307-903X
FU Swarthmore College; NIH [1R01HL091027, R15 HD080525-01]; American Heart
Association Postdoctoral Award [16POST27250075]
FX Funding was also provided by Swarthmore College and the NIH
(1R01HL091027, R15 HD080525-01). CC was supported by an American Heart
Association Postdoctoral Award (16POST27250075).
NR 83
TC 0
Z9 0
U1 5
U2 5
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 2041-9139
J9 EVODEVO
JI EvoDevo
PD AUG 31
PY 2016
VL 7
AR 21
DI 10.1186/s13227-016-0056-4
PG 16
WC Evolutionary Biology; Developmental Biology
SC Evolutionary Biology; Developmental Biology
GA DU7ZX
UT WOS:000382434200001
PM 27583126
ER
PT J
AU Vargas-Inchaustegui, DA
Ying, O
Demberg, T
Robert-Guroff, M
AF Vargas-Inchaustegui, Diego A.
Ying, Olivia
Demberg, Thorsten
Robert-Guroff, Marjorie
TI Evaluation of Functional NK Cell Responses in Vaccinated and
SIV-Infected Rhesus Macaques
SO FRONTIERS IN IMMUNOLOGY
LA English
DT Article
DE NK cell; SIV; rhesus macaque; cytokine; cytotoxicity
ID NATURAL-KILLER-CELLS; IMMUNODEFICIENCY-VIRUS-INFECTION; VIREMIC HIV-1
INFECTION; EXPRESSION; INNATE; INTERLEUKIN-15; MEMORY; CYTOTOXICITY;
INDIVIDUALS; ACTIVATION
AB NK cells are crucial components of the innate immune system due to their capacity to exert rapid cytotoxic and immunomodulatory function in the absence of prior sensitization. NK cells can become activated by exposure to target cells and/or by cytokines produced by antigen-presenting cells. In this study, we examined the effects of a simian immunodeficiency virus (SIV) vaccine regimen and subsequent SIV infection on the cytotoxic and immunomodulatory functions of circulatory NK cells. While vaccination did not significantly impact the capacity of NK cells to kill MHC-devoid 721.221 target cells, Sly-infection led to a significant decrease in target cell killing. NK cells from uninfected macaques were responsive to a low dose (5 ng/ml) of IL-15 pre-activation, leading to significant increases in their cytotoxic potential, however, NK cells from SIV-infected macaques required a higher dose (50 ng/ml) of IL-15 pre-activation in order to significantly increase their cytotoxic potential. By contrast, no differences were observed in the capacity of NK cells from vaccinated and SIV-infected macaques to respond to IL-12 and IL-18. Similarly, NK cells both before and after infection exhibited equivalent responses to Fc-mediated activation. Collectively, our results show that early SIV-infection impairs the natural cytotoxic capacity of circulatory NK cells without affecting Fc-mediated or cytokine-producing function.
C1 [Vargas-Inchaustegui, Diego A.; Ying, Olivia; Demberg, Thorsten; Robert-Guroff, Marjorie] NCI, Vaccine Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Vargas-Inchaustegui, Diego A.] NIAID, Mol Struct Sect, Viral Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
RP Vargas-Inchaustegui, DA; Robert-Guroff, M (reprint author), NCI, Vaccine Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM vargasinchausda@mail.nih.gov; guroffm@mail.nih.gov
FU Intramural Research Program of the NIH, National Cancer Institute
FX We gratefully acknowledge the animal caretakers at Advanced BioScience
Laboratories, Inc. We thank Katherine McKinnon and Sophia Brown (Vaccine
Branch Flow Core, NCI) for expert advice in Flow Cytometry; the
NIIA/NCRR Resource for Non-human Primate Immune Reagents (Emory
University, Atlanta, GA, USA) for the macaque recombinant proteins; and
Dr. Bernard A. P. Lafont (Laboratory of Molecular Microbiology, MAID)
for providing 721.221 cells. The following reagent was obtained through
the NIH Non-human Primate Reagent Resource: QD0t605 anti-CD4. This
research was supported by the Intramural Research Program of the NIH,
National Cancer Institute.
NR 41
TC 0
Z9 0
U1 0
U2 0
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 AUG 31
PY 2016
VL 7
AR 340
DI 10.3389/fimmu.2016.00340
PG 10
WC Immunology
SC Immunology
GA DU5DO
UT WOS:000382232600001
PM 27630641
ER
PT J
AU Lehmann, ML
Cooper, HA
Maric, D
Herkenham, M
AF Lehmann, Michael L.
Cooper, Hannah A.
Maric, Dragan
Herkenham, Miles
TI Social defeat induces depressive-like states and microglial activation
without involvement of peripheral macrophages
SO JOURNAL OF NEUROINFLAMMATION
LA English
DT Article
DE Stress; Microglia; Depression; Neuroimmune; Macrophage; Microglial
proliferation
ID ANXIETY-LIKE BEHAVIOR; BLOOD-BRAIN-BARRIER; MEDIAL PREFRONTAL CORTEX;
MARROW-DERIVED MICROGLIA; CENTRAL-NERVOUS-SYSTEM; ENVIRONMENTAL
ENRICHMENT; NEUROTROPHIC FACTOR; IMMUNE INTERACTIONS; ADULT
NEUROGENESIS; RAT-BRAIN
AB Background: We are interested in the causal interactions between psychological stress and activity within different compartments of the immune system. Psychosocial stress has been reported to not only alter microglia morphology but also produce anxiety-like and depressive-like effects by triggering CNS infiltration of macrophages from the periphery. We sought to test these phenomena in a somewhat different but standardized model of chronic social defeat (SD) stress.
Methods: We used a paradigm of dyadic home pairing of dominant and subordinate mice that has been validated to induce powerful anxiety-like and depressive-like effects manifested by behavior assessed in social tasks. We administered the SD stress for 3 days (acute SD) or 14 days (chronic SD) and looked for monocyte entry into the brain by three independent means, including CD45 activation states assessed by flow cytometry and tracking fluorescently tagged peripheral cells from Ccr2(wt/rfp) and Ubc(gfp/gfp) reporter mice. We further characterized the effects of SD stress on microglia using quantitative morphometric analysis, ex vivo phagocytosis assays, flow cytometry, and immunochemistry.
Results: We saw no evidence of stress-induced macrophage entry after acute or chronic defeat stress. In comparison, brain infiltration of peripheral cells did occur after endotoxin administration. Furthermore, mutant mice lacking infiltrating macrophages due to CCR2 knockout developed the same degree of chronic SD-induced depressive behavior as wildtype mice. We therefore focused more closely on the intrinsic immune cells, the microglia. Using Cx3cr1(wt/gpf) microglial reporter mice, we saw by quantitative methods that microglial morphology was not altered by stress at either time point. However, chronic SD mice had elevated numbers of CD68(hi) microglia examined by flow cytometry. CD68 is a marker for phagocytic activity. Indeed, these cells ex vivo showed elevated phagocytosis, confirming the increased activation status of chronic SD microglia. Finally, acute SD but not chronic SD increased microglial proliferation, which occurred selectively in telencephalic stress-related brain areas.
Conclusions: In the SD paradigm, changes in CNS-resident microglia numbers and activation states might represent the main immunological component of the psychosocial stress-induced depressive state.
C1 [Lehmann, Michael L.; Cooper, Hannah A.; Herkenham, Miles] NIMH, Funct Neuroanat Sect, Intramural Res Program, NIH, Bldg 35,Rm 1C911, Bethesda, MD 20892 USA.
[Maric, Dragan] NINDS, Flow Cytometry Core Facil, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
RP Lehmann, ML (reprint author), NIMH, Funct Neuroanat Sect, Intramural Res Program, NIH, Bldg 35,Rm 1C911, Bethesda, MD 20892 USA.
EM michael.lehmann@nih.gov
FU NIMH Intramural Research Program [ZIA MH001090]
FX The work was supported by the NIMH Intramural Research Program, ZIA
MH001090.
NR 89
TC 0
Z9 0
U1 9
U2 9
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 AUG 31
PY 2016
VL 13
AR 224
DI 10.1186/s12974-016-0672-x
PG 19
WC Immunology; Neurosciences
SC Immunology; Neurosciences & Neurology
GA DV4EX
UT WOS:000382879300001
PM 27581371
ER
PT J
AU Puppala, AK
French, RL
Matthies, D
Baxa, U
Subramaniam, S
Simonovic, M
AF Puppala, Anupama K.
French, Rachel L.
Matthies, Doreen
Baxa, Ulrich
Subramaniam, Sriram
Simonovic, Miljan
TI Structural basis for early-onset neurological disorders caused by
mutations in human selenocysteine synthase
SO SCIENTIFIC REPORTS
LA English
DT Article
ID PROGRESSIVE CEREBELLOCEREBRAL ATROPHY; CAUSE PONTOCEREBELLAR HYPOPLASIA;
SCATTERING DATA-ANALYSIS; SELENOPROTEIN BIOSYNTHESIS; RNA; SYSTEM; GENE;
DIFFRACTION; CLEARANCE; MECHANISM
AB Selenocysteine synthase (SepSecS) catalyzes the terminal reaction of selenocysteine, and is vital for human selenoproteome integrity. Autosomal recessive inheritance of mutations in SepSecS-Ala239Thr, Thr325Ser, Tyr334Cys and Tyr429*-induced severe, early-onset, neurological disorders in distinct human populations. Although harboring different mutant alleles, patients presented remarkably similar phenotypes typified by cerebellar and cerebral atrophy, seizures, irritability, ataxia, and extreme spasticity. However, it has remained unclear how these genetic alterations affected the structure of SepSecS and subsequently elicited the development of a neurological pathology. Herein, our biophysical and structural characterization demonstrates that, with the exception of Tyr429*, pathogenic mutations decrease protein stability and trigger protein misfolding. We propose that the reduced stability and increased propensity towards misfolding are the main causes for the loss of SepSecS activity in afflicted patients, and that these factors contribute to disease progression. We also suggest that misfolding of enzymes regulating protein synthesis should be considered in the diagnosis and study of childhood neurological disorders.
C1 [Puppala, Anupama K.; French, Rachel L.; Simonovic, Miljan] Univ Illinois, Dept Biochem & Mol Genet, Chicago, IL 60607 USA.
[Matthies, Doreen; Baxa, Ulrich; Subramaniam, Sriram] NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bldg 37, Bethesda, MD 20892 USA.
[French, Rachel L.] St Louis Univ, Dept Biochem & Mol Biol, St Louis, MO 63104 USA.
RP Simonovic, M (reprint author), Univ Illinois, Dept Biochem & Mol Genet, Chicago, IL 60607 USA.
EM msimon5@uic.edu
RI ID, BioCAT/D-2459-2012
FU National Institute of General Medical Sciences of the National
Institutes of Health [R01 GM097042, P41 GM103622]; National Cancer
Institute, NIH; DOE Office of Science [DE-AC02-06CH11357]; Michigan
Economic Development Corporation; Michigan Technology Tri-Corridor
[085P1000817]
FX We are grateful to the staff of LS-CAT beam line at APS-ANL for their
help during X-ray data collection and processing, and Dr. Srinivas
Chakravarthy for help during SAXS data collection and processing. We
thank Kaitlyn Holman for help with protein purification. This work was
supported by a grant from the National Institute of General Medical
Sciences of the National Institutes of Health R01 GM097042 (to MS) and
from the intramural program of the National Cancer Institute, NIH (to
SS). This research used resources of the Advanced Photon Source, a U.S.
Department of Energy (DOE) Office of Science User Facility operated for
the DOE Office of Science by Argonne National Laboratory under Contract
No. DE-AC02-06CH11357. BioCAT is supported by grant from the National
Institute of General Medical Sciences of the National Institutes of
Health (P41 GM103622). Use of the LS-CAT Sector 21 is supported by the
Michigan Economic Development Corporation and the Michigan Technology
Tri-Corridor (Grant 085P1000817).
NR 42
TC 0
Z9 0
U1 3
U2 4
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 AUG 31
PY 2016
VL 6
AR 32563
DI 10.1038/srep32563
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DU5JD
UT WOS:000382247100001
PM 27576344
ER
PT J
AU Pavlatou, MG
Remaley, AT
Gold, PW
AF Pavlatou, M. G.
Remaley, A. T.
Gold, P. W.
TI Klotho: a humeral mediator in CSF and plasma that influences longevity
and susceptibility to multiple complex disorders, including depression
SO TRANSLATIONAL PSYCHIATRY
LA English
DT Review
ID VITAMIN-D METABOLISM; CORONARY-ARTERY-DISEASE; CHRONIC KIDNEY-DISEASE;
CHRONIC-RENAL-FAILURE; ENDOTHELIAL DYSFUNCTION; ALPHA-KLOTHO;
PARATHYROID-HORMONE; FUNCTIONAL VARIANT; BLOOD-PRESSURE; MUTANT MICE
AB Klotho is a hormone secreted into human cerebrospinal fluid (CSF), plasma and urine that promotes longevity and influences the onset of several premature senescent phenotypes in mice and humans, including atherosclerosis, cardiovascular disease, stroke and osteoporosis. Preliminary studies also suggest that Klotho possesses tumor suppressor properties. Klotho's roles in these phenomena were first suggested by studies demonstrating that a defect in the Klotho gene in mice results in a significant decrease in lifespan. The Klotho-deficient mouse dies prematurely at 8-9 weeks of age. At 4-5 weeks of age, a syndrome resembling human ageing emerges consisting of atherosclerosis, osteoporosis, cognitive disturbances and alterations of hippocampal architecture. Several deficits in Klotho-deficient mice are likely to contribute to these phenomena. These include an inability to defend against oxidative stress in the central nervous system and periphery, decreased capacity to generate nitric oxide to sustain normal endothelial reactivity, defective Klotho-related mediation of glycosylation and ion channel regulation, increased insulin/insulin-like growth factor signaling and a disturbed calcium and phosphate homeostasis accompanied by altered vitamin D levels and ectopic calcification. Identifying the mechanisms by which Klotho influences multiple important pathways is an emerging field in human biology that will contribute significantly to understanding basic physiologic processes and targets for the treatment of complex diseases. Because many of the phenomena seen in Klotho-deficient mice occur in depressive illness, major depression and bipolar disorder represent illnesses potentially associated with Klotho dysregulation. Klotho's presence in CSF, blood and urine should facilitate its study in clinical populations.
C1 [Pavlatou, M. G.; Gold, P. W.] NIMH, Clin Neuroendocrinol Branch, NIH, Bethesda, MD 20892 USA.
[Remaley, A. T.] Natl Inst Heart Lung & Blood Inst, Lipoprotein Metab Sect, Cardiovasc & Pulm Branch, Bethesda, MD USA.
RP Gold, PW (reprint author), NIMH, Intramural NIH Res Program, NIH, Ctr Clin, Bldg 10,Room 2D-46,10 Ctr Dr MSC 1284, Bethesda, MD 20892 USA.
EM philipgold@mail.nih.gov
NR 110
TC 0
Z9 1
U1 0
U2 0
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 AUG 30
PY 2016
VL 6
AR e876
DI 10.1038/tp.2016.135
PG 9
WC Psychiatry
SC Psychiatry
GA DW1SR
UT WOS:000383423400002
PM 27576165
ER
PT J
AU Ha, HL
Kwon, T
Bak, IS
Erikson, RL
Kim, BY
Yu, DY
AF Ha, Hye-Lin
Kwon, Taeho
Bak, In Seon
Erikson, Raymond L.
Kim, Bo Yeon
Yu, Dae-Yeul
TI IGF-II induced by hepatitis B virus X protein regulates EMT via SUMO
mediated loss of E- cadherin in mice
SO ONCOTARGET
LA English
DT Article
DE hepatocellular carcinoma; hepatitis B virus X protein; IGF-II;
epithelial-mesenchymal transition; SUMOylation
ID GROWTH-FACTOR-II; EPITHELIAL-MESENCHYMAL TRANSITION;
HEPATOCELLULAR-CARCINOMA; CANCER CELLS; GENE-EXPRESSION; BREAST-CANCER;
IN-VITRO; EXTRACELLULAR CLEAVAGE; MOLECULAR-MECHANISMS; TUMOR
PROGRESSION
AB Hepatocellular carcinoma (HCC) is one of the most common cancers and a leading cause of cancer mortality. Prognosis of this disease largely depends on its stage. An Enlarged liver, due to dysplasia, may be a critical point in the multi-step progression to HCC. The mechanism underlying hepatomegaly in human and mouse models are poorly understood. We previously reported we observed enlarged liver in hepatitis B virus X protein (HBx) expressing mice (HBx mice). Here we identify the critical role of HBx induced IGF-II in hepatomegaly in mice and abnormal cell growth in human hepatoma cells. We found that HBx induced IGF-II is essential to induce epithelial-mesenchymal transition (EMT) through loss of E-cadherin. In mouse liver, loss of E-cadherin was mediated by post-translational regulation, at least in part, by protease and SUMOylation not by transcriptional regulation. In contrast, in hepatoma cell line (HepG2 cells) Akt signal pathway controls the mRNA expression level of EMT-related transcription factors, especially Twist, in addition to post-translational modification through SUMOylation. Thus, IGF-II-mediated loss of E-cadherin is central in developing hepatomegaly in mice and abnormal cell growth in the hepatoma cell line. HBx induced IGF-II represents a potential biomarker, which is also a therapeutic target in HCC.
C1 [Ha, Hye-Lin; Kwon, Taeho; Bak, In Seon; Yu, Dae-Yeul] Korea Res Inst Biosci & Biotechnol, Genome Editing Res Ctr, Dis Model Res Lab, Daejeon, South Korea.
[Ha, Hye-Lin; Yu, Dae-Yeul] Univ Sci & Technol, Dept Funct Genom, Daejeon, South Korea.
[Erikson, Raymond L.] Harvard Univ, Dept Mol & Cellular Biol, 16 Divin Ave, Cambridge, MA 02138 USA.
[Kim, Bo Yeon] Korea Res Inst Biosci & Biotechnol, Anticanc Agents Res Ctr, Ochang, Cheongwon, South Korea.
[Ha, Hye-Lin] NIAID, Immune Activat Sect, Lab Mol Immunol, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
RP Yu, DY (reprint author), Korea Res Inst Biosci & Biotechnol, Genome Editing Res Ctr, Dis Model Res Lab, Daejeon, South Korea.; Yu, DY (reprint author), Univ Sci & Technol, Dept Funct Genom, Daejeon, South Korea.; Kim, BY (reprint author), Korea Res Inst Biosci & Biotechnol, Anticanc Agents Res Ctr, Ochang, Cheongwon, South Korea.
EM bykim@kribb.re.kr; dyyu10@kribb.re.kr
FU R&D Convergence Program of the National Research Council of Science &
Technology (NST) of the Republic of Korea [CAP-15-03-KRIBB,
CAP-16-03-KRIBB]; Bio and Medical Technology Development Program of the
Ministry of Science, ICT and Future Planning (MSIP) of Korea
[NRF-2014M3A9B5073938]
FX The authors thank Dr. SM Kim for meaningful discussion. This work was
supported by the R&D Convergence Program (CAP-15-03-KRIBB and
CAP-16-03-KRIBB) of the National Research Council of Science &
Technology (NST) of the Republic of Korea and by the Bio and Medical
Technology Development Program (NRF-2014M3A9B5073938) of the Ministry of
Science, ICT and Future Planning (MSIP) of Korea.
NR 55
TC 0
Z9 0
U1 2
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 AUG 30
PY 2016
VL 7
IS 35
BP 56944
EP 56957
DI 10.18632/oncotarget.10922
PG 14
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA EA8TL
UT WOS:000386911600080
PM 27486970
ER
PT J
AU Hannah-Shmouni, F
Faucz, FR
Stratakis, CA
AF Hannah-Shmouni, Fady
Faucz, Fabio R.
Stratakis, Constantine A.
TI Alterations of Phosphodiesterases in Adrenocortical Tumors
SO FRONTIERS IN ENDOCRINOLOGY
LA English
DT Review
DE phosphodiesterases; adrenocortical tumors; adrenal hyperplasia; Cushing
syndrome; genetics; Carney complex; cAMP
ID MACRONODULAR ADRENAL-HYPERPLASIA; CYCLIC-NUCLEOTIDE PHOSPHODIESTERASES;
MCCUNE-ALBRIGHT-SYNDROME; CUSHINGS-SYNDROME; CARNEY COMPLEX;
GENETIC-HETEROGENEITY; ACTIVATING MUTATIONS; MOLECULAR-GENETICS;
SEQUENCE VARIANTS; 11A4 PDE11A
AB Alterations in the cyclic (c) AMP-dependent signaling pathway have been implicated in the majority of benign adrenocortical tumors (ACTs) causing Cushing syndrome (CS). Phosphodiesterases (PDEs) are enzymes that regulate cyclic nucleotide levels, including cyclic adenosine monophosphate (cAMP). Inactivating mutations and other functional variants in PDE11A and PDE8B, two cAMP-binding PDEs, predispose to ACTs. The involvement of these two genes in ACTs was initially revealed by a genome-wide association study in patients with micronodular bilateral adrenocortical hyperplasia. Thereafter, PDE11A or PDE8B genetic variants have been found in other ACTs, including macronodular adrenocortical hyperplasias and cortisol-producing adenomas. In addition, downregulation of PDE11A expression and inactivating variants of the gene have been found in hereditary and sporadic testicular germ cell tumors, as well as in prostatic cancer. PDEs confer an increased risk of ACT formation probably through, primarily, their action on cAMP levels, but other actions might be possible. In this report, we review what is known to date about PDE11A and PDE8B and their involvement in the predisposition to ACTs.
C1 [Hannah-Shmouni, Fady; Faucz, Fabio R.; Stratakis, Constantine A.] NICHD, Program Dev Endocrinol & Genet PDEGEN, Sect Endocrinol & Genet SEGEN, NIH, Bethesda, MD 20817 USA.
RP Stratakis, CA (reprint author), NICHD, Program Dev Endocrinol & Genet PDEGEN, Sect Endocrinol & Genet SEGEN, NIH, Bethesda, MD 20817 USA.
EM fady.hannah-shmouni@nih.gov; stratakc@mail.nih.gov
FU intramural program of the Eunice Kennedy Shriver National Institute of
Child Health and Human Development, National Institutes of Health (NIH)
[HD008920]
FX This work was supported by the intramural program of the Eunice Kennedy
Shriver National Institute of Child Health and Human Development,
National Institutes of Health (NIH), protocol HD008920.
NR 58
TC 0
Z9 0
U1 1
U2 1
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 AUG 30
PY 2016
VL 7
AR 111
DI 10.3389/fendo.2016.00111
PG 9
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA DY7ML
UT WOS:000385313300001
PM 27625633
ER
PT J
AU Smith, A
Calley, J
Mathur, S
Qian, HR
Wu, H
Farmen, M
Caiment, F
Bushel, PR
Li, JY
Fisher, C
Kirby, P
Koenig, E
Hall, DG
Watson, DE
AF Smith, Aaron
Calley, John
Mathur, Sachin
Qian, Hui-Rong
Wu, Han
Farmen, Mark
Caiment, Florian
Bushel, Pierre R.
Li, Jianying
Fisher, Craig
Kirby, Patrick
Koenig, Erik
Hall, David G.
Watson, David E.
TI The Rat microRNA body atlas; Evaluation of the microRNA content of rat
organs through deep sequencing and characterization of pancreas enriched
miRNAs as biomarkers of pancreatic toxicity in the rat and dog
SO BMC GENOMICS
LA English
DT Article
DE microRNA; Biomarkers; Deep sequencing; Tissue specific; Tissue enriched;
Pancreatic toxicity
AB Background: MicroRNAs (miRNA) are similar to 19-25 nucleotide long RNA molecules that fine tune gene expression through the inhibition of translation or degradation of the mRNA through incorporation into the RNA induced silencing complex (RISC). MicroRNAs are stable in the serum and plasma, are detectable in a wide variety of body fluids, are conserved across veterinary species and humans and are expressed in a tissue specific manner. They can be detected at low concentrations in circulation in animals and humans, generating interest in the utilization of miRNAs as serum and/or plasma based biomarkers of tissue injury. MicroRNA tissue profiling in rodents has been published, but sample an insufficient number of organs of toxicologic interest using microarray or qPCR technologies for miRNA detection. Here we impart an improved rat microRNA body atlas consisting of 21 and 23 tissues of toxicologic interest from male and female Sprague Dawley rats respectively, using Illumina miRNA sequencing. Several of the authors created a dog miRNA body atlas and we collaborated to test miRNAs conserved in rat and dog pancreas in caerulein toxicity studies utilizing both species.
Results: A rich data set is presented that more robustly defines the tissue specificity and enrichment profiles of previously published and undiscovered rat miRNAs. We generated 1,927 sequences that mapped to mature miRNAs in rat, mouse and human from miRBase and discovered an additional 1,162 rat miRNAs as compared to the current number of rat miRNAs in miRBase version 21. Tissue specific and enriched miRNAs were identified and a subset of these miRNAs were validated by qPCR for tissue specificity or enrichment. As an example of the power of this approach, we have conducted rat and dog pancreas toxicity studies and examined the levels of some tissue specific and enriched miRNAs conserved between rat and dog in the serum of each species. The studies demonstrate that conserved tissue specific/ enriched miRs-216a-5p, 375-3p, 148a-3p, 216b-5p and 141-3p are candidate biomarkers of pancreatic injury in the rat and dog.
Conclusions: A microRNA body atlas for rat and dog was useful in identifying new candidate miRNA biomarkers of organ toxicity in 2 toxicologically relevant species.
C1 [Smith, Aaron; Watson, David E.] Lilly Corp Ctr, Dept Investigat Toxicol Non Clin Safety Assessmen, Lilly Res Labs, Indianapolis, IN 46285 USA.
[Calley, John; Mathur, Sachin] Lilly Corp Ctr, Dept TTX Bioinformat, Lilly Res Labs, Indianapolis, IN 46285 USA.
[Qian, Hui-Rong; Wu, Han; Farmen, Mark] Lilly Corp Ctr, Dept Discovery & Dev Stat, Lilly Res Labs, Indianapolis, IN 46285 USA.
[Caiment, Florian] Maastricht Univ, Univ Single, Dept Toxicogen, Maastricht, Netherlands.
[Bushel, Pierre R.] NIEHS, Biostat Branch, Durham, NC USA.
[Li, Jianying] Kelly Govt Solut, Durham, NC 27709 USA.
[Fisher, Craig; Kirby, Patrick] Takeda Pharmaceut Int Co, Drug Safety Evaluat, Deerfield, IL USA.
[Koenig, Erik] Takeda Pharmaceut Int Co, Mol Pathol, Deerfield, IL USA.
[Hall, David G.] Lilly Corp Ctr, Dept Investigat Pathol, Lilly Res Labs, Indianapolis, IN 46285 USA.
RP Smith, A (reprint author), Lilly Corp Ctr, Dept Investigat Toxicol Non Clin Safety Assessmen, Lilly Res Labs, Indianapolis, IN 46285 USA.
EM smithat@lilly.com
FU Intramural Research Program of the National Institutes of Health (NIH),
National Institute of Environmental Health Sciences (NIEHS); HESI
FX This research was supported, in part, by the Intramural Research Program
of the National Institutes of Health (NIH), National Institute of
Environmental Health Sciences (NIEHS).; This HESI scientific initiative
is primarily supported by in-kind contributions (from public and private
sector participants) of time, expertise, and experimental effort. These
contributions are supplemented by direct funding (that largely supports
program infrastructure and management) that was provided by HESI's
corporate sponsors. A list of supporting organizations (public and
private) is available at
http://www.hesiglobal.org/i4a/pages/index.cfm?pageid=3311.
NR 45
TC 1
Z9 1
U1 1
U2 1
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2164
J9 BMC GENOMICS
JI BMC Genomics
PD AUG 30
PY 2016
VL 17
AR 694
DI 10.1186/s12864-016-2956-z
PG 19
WC Biotechnology & Applied Microbiology; Genetics & Heredity
SC Biotechnology & Applied Microbiology; Genetics & Heredity
GA DY3HG
UT WOS:000384980800008
PM 27576563
ER
PT J
AU Woo, HJ
Yu, CG
Kumar, K
Gold, B
Reifman, J
AF Woo, Hyung Jun
Yu, Chenggang
Kumar, Kamal
Gold, Bert
Reifman, Jaques
TI Genotype distribution-based inference of collective effects in
genome-wide association studies: insights to age-related macular
degeneration disease mechanism
SO BMC GENOMICS
LA English
DT Article
DE Genome-wide association; Machine learning; Epistasis; Single-nucleotide
polymorphism; Age-related macular degeneration
ID COMPLEMENT FACTOR-H; PENALIZED LOGISTIC-REGRESSION;
DISCRIMINANT-ANALYSIS; VARIABLE SELECTION; GENE INTERACTIONS; CANDIDATE
GENE; BREAST-CANCER; SUSCEPTIBILITY; EPISTASIS; APOPTOSIS
AB Background: Genome-wide association studies provide important insights to the genetic component of disease risks. However, an existing challenge is how to incorporate collective effects of interactions beyond the level of independent single nucleotide polymorphism (SNP) tests. While methods considering each SNP pair separately have provided insights, a large portion of expected heritability may reside in higher-order interaction effects.
Results: We describe an inference approach (discrete discriminant analysis; DDA) designed to probe collective interactions while treating both genotypes and phenotypes as random variables. The genotype distributions in case and control groups are modeled separately based on empirical allele frequency and covariance data, whose differences yield disease risk parameters. We compared pairwise tests and collective inference methods, the latter based both on DDA and logistic regression. Analyses using simulated data demonstrated that significantly higher sensitivity and specificity can be achieved with collective inference in comparison to pairwise tests, and with DDA in comparison to logistic regression. Using age-related macular degeneration (AMD) data, we demonstrated two possible applications of DDA. In the first application, a genome-wide SNP set is reduced into a small number (similar to 100) of variants via filtering and SNP pairs with significant interactions are identified. We found that interactions between SNPs with highest AMD association were epigenetically active in the liver, adipocytes, and mesenchymal stem cells. In the other application, multiple groups of SNPs were formed from the genome-wide data and their relative strengths of association were compared using cross-validation. This analysis allowed us to discover novel collections of loci for which interactions between SNPs play significant roles in their disease association. In particular, we considered pathway-based groups of SNPs containing up to similar to 10,000 variants in each group. In addition to pathways related to complement activation, our collective inference pointed to pathway groups involved in phospholipid synthesis, oxidative stress, and apoptosis, consistent with the AMD pathogenesis mechanism where the dysfunction of retinal pigment epithelium cells plays central roles.
Conclusions: The simultaneous inference of collective interaction effects within a set of SNPs has the potential to reveal novel aspects of disease association.
C1 [Woo, Hyung Jun; Yu, Chenggang; Kumar, Kamal; Reifman, Jaques] US Army Med Res & Mat Command, Biotechnol High Performance Comp Software Applica, Telemed & Adv Technol Res Ctr, Ft Detrick, MD 21702 USA.
[Gold, Bert] NCI, Lab Genom Div, Frederick, MD 21701 USA.
RP Reifman, J (reprint author), US Army Med Res & Mat Command, Biotechnol High Performance Comp Software Applica, Telemed & Adv Technol Res Ctr, Ft Detrick, MD 21702 USA.
EM jaques.reifman.civ@mail.mil
OI Kumar, Kamal/0000-0002-9470-6682
FU U.S. Army Medical Research and Materiel Command (Ft. Detrick, Maryland)
FX This work was supported by the U.S. Army Medical Research and Materiel
Command (Ft. Detrick, Maryland). The opinions and assertions contained
herein are the private views of the authors and are not to be construed
as official or as reflecting the views of the U.S. Army or of the U.S.
Department of Defense. This paper has been approved for public release
with unlimited distribution.
NR 71
TC 1
Z9 1
U1 3
U2 3
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2164
J9 BMC GENOMICS
JI BMC Genomics
PD AUG 30
PY 2016
VL 17
AR 695
DI 10.1186/s12864-016-2871-3
PG 20
WC Biotechnology & Applied Microbiology; Genetics & Heredity
SC Biotechnology & Applied Microbiology; Genetics & Heredity
GA DY3HG
UT WOS:000384980800009
PM 27576376
ER
PT J
AU Vaid, R
Dev, K
Lichten, M
Sourirajan, A
AF Vaid, Rajni
Dev, Kamal
Lichten, Michael
Sourirajan, Anuradha
TI Generation of an inducible system to express polo-like kinase, Cdc5 as
TAP fusion protein during meiosis in Saccharomyces cerevisiae
SO 3 BIOTECH
LA English
DT Article
DE Tandem affinity purification; Fusion protein; Saccharomyces cerevisiae;
Meiosis; Polo-like kinase; Cdc5; Kinase dead; Estrogen inducible;
Pachytene; Meiotic recombination; Joint molecules (JM); Substrates
ID BUDDING YEAST; SEGREGATION; DIVISION; GENE; RECOMBINATION; PURIFICATION;
CHROMOSOMES; MECHANISMS; REGULATORS; PACHYTENE
AB Tandem affinity purification (TAP) is a highly efficient method for isolation of protein complexes from endogenous biological macromolecules. TAP system consists of dual affinity tags that facilitates the sequential purification of the desired proteins expressed at their low levels in vivo. Polo-like kinases (PLK) are serine/threonine protein kinases that are the crucial regulators of cell cycle. Cdc5, the solitary PLK in budding yeast Saccharomyces cerevisiae, has diverse array of targets in cell cycle. The present study was undertaken to construct an estrogen-inducible system for expression of Cdc5-TAP to isolate the substrates of Cdc5 during meiosis, particularly, pachytene stage of meiosis I. Two yeast strains were constructed CDC5-IN (ndt80 Delta pGAL1-CDC5-TAP) and Cdc5-kinase inactive mutant (ndt80 Delta pGAL1-cdc5-N209A-TAP). The estrogen-inducible expression of Cdc5-TAP and cdc5-N209A-TAP was validated by Western analysis. The systems would serve as a valuable tool for purification of substrates binding to Cdc5-TAP by TAP affinity chromatography.
C1 [Vaid, Rajni; Dev, Kamal; Sourirajan, Anuradha] Shoolini Univ, Fac Appl Sci & Biotechnol, Solan 173212, Himachal Prades, India.
[Lichten, Michael] NCI, Lab Biochem & Mol Biol, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Sourirajan, A (reprint author), Shoolini Univ, Fac Appl Sci & Biotechnol, Solan 173212, Himachal Prades, India.
EM mlichten@helix.nih.gov; asourirajan@gmail.com
FU Department of Biotechnology (DBT), Government of India
[BT/Bio-CARe/01/616]
FX We thank Dr. Wolfgang Zachariae, Max Planck Institute of Molecular Cell
Biology and Genetics, Germany for providing genomic-tagged CDC5-TAP
yeast strains. We acknowledge the research funding to Dr. Sourirajan and
research fellowship to Ms. Vaid provided by the Department of
Biotechnology (DBT), Government of India under the project
BT/Bio-CARe/01/616. The authors would like to acknowledge Shoolini
University for infrastructural support in the research work.
NR 29
TC 0
Z9 0
U1 1
U2 1
PU SPRINGER HEIDELBERG
PI HEIDELBERG
PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY
SN 2190-5738
EI 2190-572X
J9 3 BIOTECH
JI 3 Biotech
PD AUG 30
PY 2016
VL 6
AR 185
DI 10.1007/s13205-016-0503-x
PG 6
WC Biotechnology & Applied Microbiology
SC Biotechnology & Applied Microbiology
GA DV0YR
UT WOS:000382647200001
PM 28330257
ER
PT J
AU St Laurent, B
Oy, K
Miller, B
Gasteiger, EB
Lee, E
Sovannaroth, S
Gwadz, RW
Anderson, JM
Fairhurst, RM
AF St Laurent, Brandyce
Oy, Kolthida
Miller, Becky
Gasteiger, Elizabeth B.
Lee, Eunjae
Sovannaroth, Siv
Gwadz, Robert W.
Anderson, Jennifer M.
Fairhurst, Rick M.
TI Cow-baited tents are highly effective in sampling diverse Anopheles
malaria vectors in Cambodia
SO MALARIA JOURNAL
LA English
DT Article
DE Anopheles; Cambodia; Trap; Outdoor transmission; Malaria; Vector
ID PLASMODIUM-FALCIPARUM MALARIA; HUMAN LANDING CATCHES; MOSQUITOS DIPTERA;
WESTERN THAILAND; SOUTHEAST-ASIA; ENDEMIC AREA; IDENTIFICATION;
TRANSMISSION; POPULATIONS; RESISTANCE
AB Background: The accurate monitoring and evaluation of malaria vectors requires efficient sampling. The objective of this study was to compare methods for sampling outdoor-biting Anopheles mosquitoes in Cambodia.
Methods: In the Cambodian provinces of Pursat, Preah Vihear, and Ratanakiri, six different mosquito trapping methods were evaluated: human landing collection (HLC), human-baited tent (HBT), cow-baited tent (CBT), CDC miniature light trap (LT), CDC miniature light trap baited with molasses and yeast (LT-M), and barrier fence (F) in a Latin square design during four or six consecutive nights at the height of the malaria transmission season.
Results: Using all traps, a total of 507, 1175, and 615 anophelines were collected in Pursat, Preah Vihear, and Ratanakiri, respectively. CBTs captured 10- to 20-fold more anophelines per night than the other five sampling methods. All 2297 Anopheles mosquitoes were morphologically identified and molecularly typed using standard morphological keys and sequencing the rDNA ITS2 region to distinguish cryptic species, respectively. Overall, an extremely diverse set of 27 known Anopheles species was sampled. CBTs captured the same molecular species that HLCs and the other four traps did, as well as additional species. Nine specimens representing five Anopheles species (Anopheles hyrcanus, Anopheles barbirostris sensu stricto, Anopheles barbirostris clade III, Anopheles nivipes, and Anopheles peditaeniatus) were infected with Plasmodium falciparum and were exclusively captured in CBTs.
Conclusions: These data indicate that cow-baited tents are highly effective in sampling diverse Anopheles malaria vectors in Cambodia. This sampling method captured high numbers of anophelines with limited sampling effort and greatly reduced human exposure to mosquito bites compared to the gold-standard human landing collection.
C1 [St Laurent, Brandyce; Miller, Becky; Gasteiger, Elizabeth B.; Lee, Eunjae; Gwadz, Robert W.; Anderson, Jennifer M.; Fairhurst, Rick M.] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA.
[Oy, Kolthida; Sovannaroth, Siv] Natl Ctr Parasitol Entomol & Malaria Control, Phnom Penh 12101, Cambodia.
RP St Laurent, B; Fairhurst, RM (reprint author), NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA.
EM brandyce.stlaurent@nih.gov; rfairhurst@niaid.nih.gov
OI St. Laurent, Brandyce/0000-0002-2957-5364
FU Intramural Research Program, National Institute of Allergy and
Infectious Diseases, US National Institutes of Health
FX This study was funded by the Intramural Research Program, National
Institute of Allergy and Infectious Diseases, US National Institutes of
Health.
NR 34
TC 0
Z9 0
U1 3
U2 4
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1475-2875
J9 MALARIA J
JI Malar. J.
PD AUG 30
PY 2016
VL 15
AR 440
DI 10.1186/s12936-016-1488-y
PG 11
WC Infectious Diseases; Parasitology; Tropical Medicine
SC Infectious Diseases; Parasitology; Tropical Medicine
GA DU9KM
UT WOS:000382535900001
PM 27577697
ER
PT J
AU Langenfurth, A
Gu, S
Bautze, V
Zhang, CY
Neumann, JE
Schuller, U
Stock, K
Wolf, SA
Maier, AM
Mastrella, G
Pak, A
Cheng, HW
Kalin, RE
Holmbeck, K
Strotmann, J
Kettenmann, H
Glass, R
AF Langenfurth, Anika
Gu, Song
Bautze, Verena
Zhang, Caiyi
Neumann, Julia E.
Schueller, Ulrich
Stock, Kristin
Wolf, Susanne A.
Maier, Anna-Maria
Mastrella, Giorgia
Pak, Andrew
Cheng, Hongwei
Kaelin, Roland E.
Holmbeck, Kenn
Strotmann, Joerg
Kettenmann, Helmut
Glass, Rainer
TI Decreased demand for olfactory periglomerular cells impacts on neural
precursor cell viability in the rostral migratory stream
SO SCIENTIFIC REPORTS
LA English
DT Article
ID ADULT MAMMALIAN BRAIN; SUBVENTRICULAR ZONE; BULB NEUROGENESIS;
STEM-CELLS; MICE; RAT; HIPPOCAMPAL; DEATH; PLASTICITY; NEURONS
AB The subventricular zone (SVZ) provides a constant supply of new neurons to the olfactory bulb (OB). Different studies have investigated the role of olfactory sensory input to neural precursor cell (NPC) turnover in the SVZ but it was not addressed if a reduced demand specifically for periglomerular neurons impacts on NPC-traits in the rostral migratory stream (RMS). We here report that membrane type-1 matrix metalloproteinase (MT1-MMP) deficient mice have reduced complexity of the nasal turbinates, decreased sensory innervation of the OB, reduced numbers of olfactory glomeruli and reduced OB-size without alterations in SVZ neurogenesis. Large parts of the RMS were fully preserved in MT1-MMP-deficient mice, but we detected an increase in cell death-levels and a decrease in SVZ-derived neuroblasts in the distal RMS, as compared to controls. BrdU-tracking experiments showed that homing of NPCs specifically to the glomerular layer was reduced in MT1-MMP-deficient mice in contrast to controls while numbers of tracked cells remained equal in other OB-layers throughout all experimental groups. Altogether, our data show the demand for olfactory interneurons in the glomerular layer modulates cell turnover in the RMS, but has no impact on subventricular neurogenesis.
C1 [Langenfurth, Anika; Stock, Kristin; Wolf, Susanne A.; Kettenmann, Helmut] Helmholtz Assoc, Max Delbruck Ctr Mol Med, Cellular Neurosci, Robert Rossle Str 10, Berlin, Germany.
[Langenfurth, Anika] Charite, Dept Psychiat & Psychotherapy Neuropsychiat, Charitepl 1, Berlin, Germany.
[Gu, Song; Zhang, Caiyi; Mastrella, Giorgia; Kaelin, Roland E.; Glass, Rainer] Univ Munich, Neurosurg Res, Marchioninistr 15, Munich, Germany.
[Gu, Song; Cheng, Hongwei] Anhui Med Univ, Affiliated Hosp 1, Dept Neurosurg, Hefei 230022, Anhui, Peoples R China.
[Bautze, Verena; Maier, Anna-Maria; Strotmann, Joerg] Univ Hohenheim, Inst Physiol, Garbenstr 30, Hohenheim, Germany.
[Neumann, Julia E.; Schueller, Ulrich] Univ Munich, Ctr Neuropathol, Feodor Lynen Str 23, Munich, Germany.
[Neumann, Julia E.; Schueller, Ulrich] Univ Med Ctr, Inst Neuropathol, Hamburg, Germany.
[Neumann, Julia E.; Schueller, Ulrich] Res Inst Childrens Canc Ctr, Hamburg, Germany.
[Schueller, Ulrich] Univ Med Ctr Hamburg Eppendorf, Dept Pediat Hematol & Oncol, D-20264 Hamburg, Germany.
[Pak, Andrew; Holmbeck, Kenn] NIDCR, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD 20892 USA.
RP Glass, R (reprint author), Univ Munich, Neurosurg Res, Marchioninistr 15, Munich, Germany.
EM rainer.glass@med.uni-muenchen.de
FU Klinisches Ausbildungsprogramm (KAP); Neurocure; DFG [Str 619/5-1,
SPP1392, GL691/2, SFB824]; Wilhelm Sander Stiftung; Anni-Hofmann
Stiftung; Verein zur Forderung von Wissenschaft und Forschung an der
Medizinischen Fakultat (WiFoMed) der LMU Munchen; Curt Bohnewandt Fonds;
Friedrich-Baur-Stiftung; Familie Mehdorn Stiftung
FX We are thankful to Kazuaki Yoshikawa (Osaka University, Osaka, Japan)
for providing us with the guinea pig anti-Dlx2 antibody. A.L. was
supported by a scholarship from the "Klinisches Ausbildungsprogramm
(KAP)". This research was supported by Neurocure. J.S. R.G. and R.E.K.
gratefully acknowledge funding by the DFG (Str 619/5-1; SPP1392;
GL691/2; SFB824), the Wilhelm Sander Stiftung, the Anni-Hofmann
Stiftung, Verein zur Forderung von Wissenschaft und Forschung an der
Medizinischen Fakultat (WiFoMed) der LMU Munchen, the Curt Bohnewandt
Fonds, the Friedrich-Baur-Stiftung and the Familie Mehdorn Stiftung.
NR 45
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 2045-2322
J9 SCI REP-UK
JI Sci Rep
PD AUG 30
PY 2016
VL 6
AR 32203
DI 10.1038/srep32203
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DU5PH
UT WOS:000382263300001
PM 27573347
ER
PT J
AU van der Laan, SW
Fall, T
Soumare, A
Teumer, A
Sedaghat, S
Baumert, J
Zabaneh, D
van Setten, J
Isgum, I
Galesloot, TE
Arpegard, J
Amouyel, P
Trompet, S
Waldenberger, M
Dorr, M
Magnusson, PK
Giedraitis, V
Larsson, A
Morris, AP
Felix, JF
Morrison, AC
Franceschini, N
Bis, JC
Kavousi, M
O'Donnell, C
Drenos, F
Tragante, V
Munroe, PB
Malik, R
Dichgans, M
Worrall, BB
Erdmann, J
Nelson, CP
Samani, NJ
Schunkert, H
Marchini, J
Patel, RS
Hingorani, AD
Lind, L
Pedersen, NL
de Graaf, J
Kiemeney, LALM
Baumeister, SE
Franco, OH
Hofman, A
Uitterlinden, AG
Koenig, W
Meisinger, C
Peters, A
Thorand, B
Jukema, JW
Eriksen, BO
Toft, I
Wilsgaard, T
Onland-Moret, NC
van der Schouw, YT
Debette, S
Kumari, M
Svensson, P
van der Harst, P
Kivimaki, M
Keating, BJ
Sattar, N
Dehghan, A
Reiner, AP
Ingelsson, E
den Ruijter, HM
de Bakker, PIW
Pasterkamp, G
Arnlov, J
Holmes, MV
Asselbergs, FW
AF van der Laan, Sander W.
Fall, Tove
Soumare, Aicha
Teumer, Alexander
Sedaghat, Sanaz
Baumert, Jens
Zabaneh, Delilah
van Setten, Jessica
Isgum, Ivana
Galesloot, Tessel E.
Arpegard, Johannes
Amouyel, Philippe
Trompet, Stella
Waldenberger, Melanie
Doerr, Marcus
Magnusson, Patrik K.
Giedraitis, Vilmantas
Larsson, Anders
Morris, Andrew P.
Felix, Janine F.
Morrison, Alanna C.
Franceschini, Nora
Bis, Joshua C.
Kavousi, Maryam
O'Donnell, Christopher
Drenos, Fotios
Tragante, Vinicius
Munroe, Patricia B.
Malik, Rainer
Dichgans, Martin
Worrall, Bradford B.
Erdmann, Jeanette
Nelson, Christopher P.
Samani, Nilesh J.
Schunkert, Heribert
Marchini, Jonathan
Patel, Riyaz S.
Hingorani, Aroon D.
Lind, Lars
Pedersen, Nancy L.
de Graaf, Jacqueline
Kiemeney, Lambertus A. L. M.
Baumeister, Sebastian E.
Franco, Oscar H.
Hofman, Albert
Uitterlinden, Andre G.
Koenig, Wolfgang
Meisinger, Christa
Peters, Annette
Thorand, Barbara
Jukema, J. Wouter
Eriksen, Bjorn Odvar
Toft, Ingrid
Wilsgaard, Tom
Onland-Moret, N. Charlotte
van der Schouw, Yvonne T.
Debette, Stephanie
Kumari, Meena
Svensson, Per
van der Harst, Pim
Kivimaki, Mika
Keating, Brendan J.
Sattar, Naveed
Dehghan, Abbas
Reiner, Alex P.
Ingelsson, Erik
den Ruijter, Hester M.
de Bakker, Paul I. W.
Pasterkamp, Gerard
Arnlov, Johan
Holmes, Michael V.
Asselbergs, Folkert W.
TI Cystatin C and Cardiovascular Disease A Mendelian Randomization Study
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Article
DE coronary heart disease; genetics; heart failure; ischemic stroke
ID CHRONIC KIDNEY-DISEASE; GENOME-WIDE ASSOCIATION;
CORONARY-ARTERY-DISEASE; INCIDENT HEART-FAILURE; BODY-MASS INDEX;
SUSCEPTIBILITY LOCI; CHARGE CONSORTIUM; COMMON VARIANTS;
ISCHEMIC-STROKE; RISK
AB BACKGROUND Epidemiological studies show that high circulating cystatin C is associated with risk of cardiovascular disease (CVD), independent of creatinine-based renal function measurements. It is unclear whether this relationship is causal, arises from residual confounding, and/or is a consequence of reverse causation.
OBJECTIVES The aim of this study was to use Mendelian randomization to investigate whether cystatin C is causally related to CVD in the general population.
METHODS We incorporated participant data from 16 prospective cohorts (n = 76,481) with 37,126 measures of cystatin C and added genetic data from 43 studies (n = 252,216) with 63,292 CVD events. We used the common variant rs911119 in CST3 as an instrumental variable to investigate the causal role of cystatin C in CVD, including coronary heart disease, ischemic stroke, and heart failure.
RESULTS Cystatin C concentrations were associated with CVD risk after adjusting for age, sex, and traditional risk factors (relative risk: 1.82 per doubling of cystatin C; 95% confidence interval [CI]: 1.56 to 2.13; p = 2.12 x 10(-14)). The minor allele of rs911119 was associated with decreased serum cystatin C (6.13% per allele; 95% CI: 5.75 to 6.50; p = 5.95 x 10(-211)), explaining 2.8% of the observed variation in cystatin C. Mendelian randomization analysis did not provide evidence fora causal role of cystatin C, with a causal relative risk for CVD of 1.00 per doubling cystatin C (95% CI: 0.82 to 1.22; p = 0,994), which was statistically different from the observational estimate (p = 1.6 x 10(-5)). A causal effect of cystatin C was not detected for any individual component of CVD.
CONCLUSIONS Mendelian randomization analyses did not support a causal role of cystatin C in the etiology of CVD. As such, therapeutics targeted at lowering circulating cystatin C are unlikely to be effective in preventing CVD. (C) 2016 The Authors. Published by Elsevier Inc. on behalf of the American College of Cardiology Foundation. This is an open access article under the CC BY-NC-ND license.
C1 [van der Laan, Sander W.; van Setten, Jessica; den Ruijter, Hester M.; Pasterkamp, Gerard] Univ Med Ctr Utrecht, Div Heart & Lungs, Lab Expt Cardiol, Heidelberglaan 100, NL-3584 CX Utrecht, Netherlands.
[Fall, Tove; Arnlov, Johan] Uppsala Univ, Dept Med Sci, Cardiovasc Epidemiol, Uppsala, Sweden.
[Soumare, Aicha; Debette, Stephanie] Univ Bordeaux, INSERM, U1219, Team Vintage, Bordeaux, France.
[Teumer, Alexander; Baumeister, Sebastian E.] Univ Med Greifswald, Inst Community Med, Dept SHIP KEF, Greifswald, Germany.
[Teumer, Alexander; Doerr, Marcus; Koenig, Wolfgang; Peters, Annette] German Ctr Cardiovasc Res, DZHK, Partner Site, Greifswald, Germany.
[Sedaghat, Sanaz; Felix, Janine F.; Kavousi, Maryam; Franco, Oscar H.; Hofman, Albert; Dehghan, Abbas] Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands.
[Baumert, Jens; Waldenberger, Melanie; Meisinger, Christa; Peters, Annette; Thorand, Barbara] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol 2, Neuherberg, Germany.
[Zabaneh, Delilah] UCL, Dept Genet Environm & Evolut, London, England.
[Zabaneh, Delilah] UCL, Genet Inst, London, England.
[Isgum, Ivana] Univ Med Ctr Utrecht, Image Sci Inst, Utrecht, Netherlands.
[Galesloot, Tessel E.; de Graaf, Jacqueline; Kiemeney, Lambertus A. L. M.] Radboud Univ Nijmegen, Med Ctr, Radboud Inst Hlth Sci, Nijmegen, Netherlands.
[Arpegard, Johannes; Svensson, Per] Karolinska Univ Hosp Solna, Dept Emergency Med, Stockholm, Sweden.
[Arpegard, Johannes; Svensson, Per] Karolinska Inst, Dept Med Solna, Stockholm, Sweden.
[Amouyel, Philippe] Univ Lille, INSERM, Lille, France.
[Amouyel, Philippe] Inst Pasteur, Lille, France.
[Trompet, Stella; Jukema, J. Wouter] Leiden Univ, Med Ctr, Dept Cardiol P C5, Leiden, Netherlands.
[Trompet, Stella] Leiden Univ, Med Ctr, Dept Gerontol & Geriatr, Leiden, Netherlands.
[Waldenberger, Melanie] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Res Unit Mol Epidemiol, Neuherberg, Germany.
[Doerr, Marcus] Univ Med Greifswald, Dept Internal Med B, Greifswald, Germany.
[Magnusson, Patrik K.; Pedersen, Nancy L.] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
[Giedraitis, Vilmantas] Uppsala Univ, Dept Publ Health Geriatr, Uppsala, Sweden.
[Larsson, Anders; Lind, Lars] Uppsala Univ, Dept Med Sci, Uppsala, Sweden.
[Morris, Andrew P.] Univ Liverpool, Dept Biostat, Liverpool, Merseyside, England.
[Morris, Andrew P.] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.
[Morrison, Alanna C.] Univ Texas Hlth Sci Ctr Houston, Dept Epidemiol Human Genet & Environm Sci, Houston, TX 77030 USA.
[Franceschini, Nora] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA.
[Bis, Joshua C.] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA.
[O'Donnell, Christopher] Boston Vet Adm Healthcare, Dept Cardiol, West Roxbury, MA USA.
[O'Donnell, Christopher] NHLBI, Framingham Heart Study, Framingham, MA USA.
[Drenos, Fotios] UCL, Inst Cardiovasc Sci, Ctr Cardiovasc Genet, London, England.
[Drenos, Fotios] Univ Bristol, Sch Social & Community Med, MRC Integrat Epidemiol Unit, Bristol, Avon, England.
[Tragante, Vinicius; Asselbergs, Folkert W.] Univ Med Ctr Utrecht, Dept Cardiol, Div Heart & Lungs, Heidelberglaan 100, NL-3584 CX Utrecht, Netherlands.
[Munroe, Patricia B.] Queen Mary Univ London, William Harvey Res Inst, Natl Inst Hlth Res, Cardiovasc Biomed Res Unit, London, England.
[Malik, Rainer; Dichgans, Martin] Univ Munich, Klinikum Univ Munchen, Inst Stroke & Dementia Res, Munich, Germany.
[Dichgans, Martin] Munich Cluster Syst Neurol SyNergy, Munich, Germany.
[Worrall, Bradford B.] Univ Virginia, Dept Neurol, Charlottesville, VA USA.
[Worrall, Bradford B.] Univ Virginia, Dept Hlth Evaluat Sci, Charlottesville, VA USA.
[Erdmann, Jeanette] Univ Lubeck, Inst Integrat & Expt Genom, Lubeck, Germany.
[Nelson, Christopher P.; Samani, Nilesh J.] Univ Leicester, Glenfield Hosp, British Heart Fdn Cardiovasc, Res Ctr,Dept Cardiovasc Sci, Leicester, Leics, England.
[Nelson, Christopher P.; Samani, Nilesh J.] Glenfield Hosp, Natl Inst Hlth Res Leicester, Cardiovasc Biomed Res Unit, Leicester, Leics, England.
[Schunkert, Heribert; Koenig, Wolfgang] Tech Univ Munich, Deutsch Herzzentrum Munchen, Munich, Germany.
[Schunkert, Heribert] German Ctr Cardiovasc Res, DZHK, Munich Heart Alliance, Partner Site, Munich, Germany.
[Marchini, Jonathan] Univ Oxford, Dept Stat, Oxford, England.
[Patel, Riyaz S.; Hingorani, Aroon D.] UCL, Inst Cardiovasc Sci, Genet Epidemiol Res Grp, London, England.
[Patel, Riyaz S.] Barts Heart Ctr, London, England.
[Patel, Riyaz S.] UCL, Farr Inst Hlth Informat, London, England.
[de Graaf, Jacqueline] Radboud Univ Nijmegen, Med Ctr, Dept Internal Med, Nijmegen, Netherlands.
[Baumeister, Sebastian E.] Univ Regensburg, Inst Epidemiol & Prevent Med, Regensburg, Germany.
[Uitterlinden, Andre G.] Erasmus Univ, Med Ctr, Dept Internal Med, Rotterdam, Netherlands.
[Koenig, Wolfgang] Univ Ulm, Med Ctr, Dept Internal Med Cardiol 2, Ulm, Germany.
[Jukema, J. Wouter; van der Harst, Pim; Asselbergs, Folkert W.] ICIN Netherlands Heart Inst, Durrer Ctr Cardiogenet Res, Utrecht, Netherlands.
[Eriksen, Bjorn Odvar] UiT Arctic Univ Norway, Metab & Renal Res Grp, Tromso, Norway.
[Eriksen, Bjorn Odvar; Toft, Ingrid] Univ Hosp North Norway, Nephrol Sect, Tromso, Norway.
[Wilsgaard, Tom] UiT Arctic Univ Norway, Dept Community Med, Tromso, Norway.
[Onland-Moret, N. Charlotte; van der Schouw, Yvonne T.; de Bakker, Paul I. W.] Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands.
[Kumari, Meena] Univ Essex, Biol & Social Epidemiol, Inst Social & Econ Res, Colchester CO4 3SQ, Essex, England.
[van der Harst, Pim] Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, Groningen, Netherlands.
[van der Harst, Pim] Univ Groningen, Univ Med Ctr Groningen, Dept Genet, Groningen, Netherlands.
[Kivimaki, Mika] UCL, Dept Epidemiol & Publ Hlth, London, England.
[Keating, Brendan J.] Univ Penn, Dept Surg, Div Transplantat, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Sattar, Naveed] Univ Glasgow, Glasgow, Lanark, Scotland.
[Reiner, Alex P.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
[Ingelsson, Erik] Uppsala Univ, Mol Epidemiol & Sci Life Lab, Dept Med Sci, Uppsala, Sweden.
[Ingelsson, Erik] Stanford Univ, Dept Med, Sch Med, Div Cardiovasc Med, Stanford, CA 94305 USA.
[de Bakker, Paul I. W.] Univ Med Ctr Utrecht, Ctr Mol Med, Dept Med Genet, Utrecht, Netherlands.
[Pasterkamp, Gerard] Univ Med Ctr Utrecht, Div Labs & Pharm, Lab Clin Chem & Hematol, Utrecht, Netherlands.
[Holmes, Michael V.] Univ Oxford, Nuffield Dept Populat Hlth, Clin Trial Serv Unit, Richard Doll Bldg,Old Rd Campus,Roosevelt Dr, Oxford OX3 7LF, England.
[Holmes, Michael V.] Univ Oxford, Nuffield Dept Populat Hlth, Epidemiol Studies Unit CTSU, Richard Doll Bldg,Old Rd Campus,Roosevelt Dr, Oxford OX3 7LF, England.
[Asselbergs, Folkert W.] UCL, Fac Populat Hlth Sci, Inst Cardiovasc Sci, London, England.
RP van der Laan, SW (reprint author), Univ Med Ctr Utrecht, Div Heart & Lungs, Lab Expt Cardiol, Heidelberglaan 100, NL-3584 CX Utrecht, Netherlands.; Asselbergs, FW (reprint author), Univ Med Ctr Utrecht, Dept Cardiol, Div Heart & Lungs, Heidelberglaan 100, NL-3584 CX Utrecht, Netherlands.; Holmes, MV (reprint author), Univ Oxford, Nuffield Dept Populat Hlth, Clin Trial Serv Unit, Richard Doll Bldg,Old Rd Campus,Roosevelt Dr, Oxford OX3 7LF, England.; Holmes, MV (reprint author), Univ Oxford, Nuffield Dept Populat Hlth, Epidemiol Studies Unit CTSU, Richard Doll Bldg,Old Rd Campus,Roosevelt Dr, Oxford OX3 7LF, England.
EM s.w.vanderlaan-2@umcutrecht.nl; michael.holmes@ndph.ox.ac.uk;
f.w.asselbergs@umcutrecht.nl
RI Waldenberger, Melanie/B-5355-2014; Peters, Annette/A-6117-2011;
Onland-Moret, N. Charlotte/G-9185-2011; Magnusson, Patrik/C-4458-2017;
OI Waldenberger, Melanie/0000-0003-0583-5093; van der Laan, Sander
W./0000-0001-6888-1404; Kumari, Meena/0000-0001-9716-1035; Svensson,
Per/0000-0003-0372-6272; Peters, Annette/0000-0001-6645-0985
FU Pie Medical Imaging; 3Mensio Medical Imaging B.V.; NWO and Foundation
for Technological Sciences [12726]; Stockholm County Council (combined
clinical residency and PhD training program); Servier; Hoffman Laroche;
Total; Genoscreen; Alzprotect; Fondation Plan Alzheimer; Takeda;
Wellcome Trust Senior Fellow in Basic Biomedical Science [WT098017];
National Institute of Neurological Disorders and Stroke [U-01 N5069208];
National Human Genome Research Institute [U-01 HG005160]; British Heart
Foundation (BHF); National Institute for Health Research Senior
Investigator; BHF; Nestle Nutrition (Nestec Ltd.); Metagenics Inc.; AXA;
BHF Intermediate Fellowship; NGFNplus [01GS0834]; Abbott; Roche
Diagnostics; Beckmann; Singulex; Netherlands Heart Foundation [2001 D
032]; Swedish Society of Medicine [SLS-412071]; Medical Research Council
[K013351]; Economic and Social Research Council; National Institutes of
Health [HL36310]; Netherlands Organization for Scientific Research (NWO)
[916.12.154]; EUR Fellowship; Goran Gustafsson Foundation; Swedish
Heart-Lung Foundation [20140422]; Knut and Alice Wallenberg Foundation;
European Research Council [ERC-StG-335395]; Swedish Diabetes Foundation
(Diabetesfonden) [2013-024]; Swedish Research Council [2012-1397,
2012-1727, 2012-2215]; Swedish Heart-Lung Foundation; Thureus
Foundation; Marianne and Marcus Wallenberg Foundation; Dalarna
University; Uppsala University; Dekker scholarship-Junior Staff Member
[2014T001]; European Union Seventh Framework Programme FP7
[HEALTH-F2-2013-601456]; Netherlands Heart Foundation; UCL Hospitals
National Institute for Health Research Biomedical Research Centre
FX The individual study sponsor(s) had no role in the study design; in the
collection, analysis, and interpretation of data; in the writing of the
report; and in the decision to submit the paper for publication. Dr.
Isgum is supported by research grants from Pie Medical Imaging, 3Mensio
Medical Imaging B.V., the NWO and Foundation for Technological Sciences
under Project 12726, The Netherlands Organization for Health Research
and Development, and the Dutch Cancer Society. Dr. Arpegard has received
funding through the Stockholm County Council (combined clinical
residency and PhD training program). Dr. Amouyel has received personal
fees from Servier, Hoffman Laroche, Total, Genoscreen, Alzprotect,
Fondation Plan Alzheimer, and Takeda outside of the submitted work; and
has shares in Genoscreen. Dr. Morris is a Wellcome Trust Senior Fellow
in Basic Biomedical Science under grant number WT098017. Dr. Worrall has
received compensation for his role as deputy editor of the Journal of
Neurology; and has received National Institutes of Health funding
through the National Institute of Neurological Disorders and Stroke
(U-01 N5069208) and National Human Genome Research Institute (U-01
HG005160). Dr. Samani is supported by the British Heart Foundation
(BHF); and is a National Institute for Health Research Senior
Investigator. Dr. Nelson is supported by the BHF. Dr. Franco works in
ErasmusAGE, a center for aging research across the life course funded by
Nestle Nutrition (Nestec Ltd.), Metagenics Inc., and AXA; Nestle
Nutrition (Nestec Ltd.), Metagenics Inc., and AXA had no role in design
and conduct of the study; collection, management, analysis, and
interpretation of the data; and preparation, review, or approval of the
manuscript. Dr. Patel is supported by a BHF Intermediate Fellowship. Dr.
Koenig has received funds through NGFNplus, project number 01GS0834; has
received research grants from Abbott, Roche Diagnostics, Beckmann, and
Singulex; has received honorarium for lectures from AstraZeneca,
Novartis, Merck Sharp & Dohme, Amgen, and Actavis; and has served as a
consultant for Novartis, Pfizer, The Medicines Company, Amgen,
AstraZeneca, Merck Sharp & Dohme, and GlaxoSmithKline. Dr. Jukema is an
Established Clinical Investigator of the Netherlands Heart Foundation
(grant 2001 D 032). Dr. Svensson has received a grant from the Swedish
Society of Medicine (SLS-412071). Dr. Kivimaki has received funding
through the Medical Research Council (K013351), Economic and Social
Research Council, and National Institutes of Health (HL36310). Dr.
Dehghan is supported by a Netherlands Organization for Scientific
Research (NWO) grant (VENI, 916.12.154) and the EUR Fellowship; and has
received consultancy and research support from Metagenics Inc. (outside
the scope of this work). Dr. Ingelsson is supported by grants from Goran
Gustafsson Foundation, Swedish Heart-Lung Foundation (20140422), Knut
and Alice Wallenberg Foundation (Knut och Alice Wallenbergs Stiftelse),
European Research Council (ERC-StG-335395), Swedish Diabetes Foundation
(Diabetesfonden; grant no. 2013-024), and the Swedish Research Council
(VR; grant no. 2012-1397). Dr. de Bakker is an employee of Vertex
Pharmaceuticals. Dr. Arnlov was funded by the Swedish Research Council
(2012-1727, 2012-2215), Swedish Heart-Lung Foundation, Thureus
Foundation, the Marianne and Marcus Wallenberg Foundation, Dalarna
University, and Uppsala University. Dr.; Asselbergs is supported by a
Dekker scholarship-Junior Staff Member 2014T001-Netherlands Heart
Foundation and UCL Hospitals National Institute for Health Research
Biomedical Research Centre. The research leading to these results has
received funding from the European Union Seventh Framework Programme
FP7/2007-2013 under grant agreement no HEALTH-F2-2013-601456
(CVgenes-at-target). All other authors have reported that they have no
relationships relevant to the contents of this paper to disclose.
NR 46
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U1 10
U2 11
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 AUG 30
PY 2016
VL 68
IS 9
BP 934
EP 945
DI 10.1016/j.jacc.2016.05.092
PG 12
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA DU6GS
UT WOS:000382312900009
PM 27561768
ER
PT J
AU Nugent, AC
Robinson, SE
Coppola, R
Zarate, CA
AF Nugent, Allison C.
Robinson, Stephen E.
Coppola, Richard
Zarate, Carlos A., Jr.
TI Preliminary differences in resting state MEG functional connectivity
pre- and post-ketamine in major depressive disorder
SO PSYCHIATRY RESEARCH-NEUROIMAGING
LA English
DT Article
DE Magnetoencephalography (MEG); Depression; Ketamine; Resting state;
Connectivity; Independent components analysis (ICA)
ID RAPID ANTIDEPRESSANT RESPONSE; TREATMENT-RESISTANT DEPRESSION; DEFAULT
MODE NETWORK; ACTING ANTIDEPRESSANTS; HEALTHY-VOLUNTEERS; NEURAL
ACTIVITY; CINGULATE; GLUTAMATE; CORTEX; FMRI
AB Functional neuroimaging techniques including magnetoencephalography (MEG) have demonstrated that the brain is organized into networks displaying correlated activity. Group connectivity differences between healthy controls and participants with major depressive disorder (MDD) can be detected using temporal independent components analysis (ICA) on beta-bandpass filtered Hilbert envelope MEG data. However, the response of these networks to treatment is unknown. Ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, exerts rapid antidepressant effects. We obtained MEG recordings before and after open-label infusion of 0.5mg/kg ketamine in MDD subjects (N=13) and examined networks previously shown to differ between healthy individuals and those with MDD. Connectivity between the amygdala and an insulo-temporal component decreased post-ketamine in MDD subjects towards that observed in control subjects at baseline. Decreased baseline connectivity of the subgenual anterior cingulate cortex (sgACC) with a bilateral precentral network had previously been observed in MDD compared to healthy controls, and the change in connectivity post-ketamine was proportional to the change in sgACC glucose metabolism in a subset (N=8) of subjects receiving [11F]FDG-PET imaging. Ketamine appeared to reduce connectivity, regardless of whether connectivity was abnormally high or low compared to controls at baseline. These preliminary findings suggest that sgACC connectivity may be directly related to glutamate levels. Published by Elsevier Ireland Ltd.
C1 [Nugent, Allison C.; Zarate, Carlos A., Jr.] NIMH, Expt Therapeut & Pathophysiol Branch, NIH, 9000 Rockville Pike,MSC 1030, Bethesda, MD 20892 USA.
[Robinson, Stephen E.; Coppola, Richard] NIMH, NIMH Magnetoencephalog Core Facil, NIH, Bethesda, MD 20892 USA.
RP Nugent, AC (reprint author), NIMH, Expt Therapeut & Pathophysiol Branch, NIH, 9000 Rockville Pike,MSC 1030, Bethesda, MD 20892 USA.
EM nugenta@mail.nih.gov
FU Intramural Research Program at the National Institute of Mental Health;
National Institutes of Health (IRP-NIMH-NIH) [ZIA-MH002927-04]; Brain &
Behavior Mood Disorders Research Award
FX Funding for this work was supported by the Intramural Research Program
at the National Institute of Mental Health, National Institutes of
Health (IRP-NIMH-NIH; Clinical Trials Identifier: NCT00024635
(ZIA-MH002927-04)), by a NARSAD Independent Investigator to Dr. Zarate,
and by a Brain & Behavior Mood Disorders Research Award to Dr. Zarate.
The authors thank the 7SE research unit and staff for their support.
loline Henter, MA (NIMH) provided invaluable editorial assistance.
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PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0925-4927
EI 1872-7506
J9 PSYCHIAT RES-NEUROIM
JI Psychiatry Res. Neuroimaging
PD AUG 30
PY 2016
VL 254
BP 56
EP 66
DI 10.1016/j.pscychresns.2016.06.006
PG 11
WC Clinical Neurology; Neuroimaging; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA DU6HU
UT WOS:000382316000009
PM 27362845
ER
PT J
AU Szczepanik, J
Nugent, AC
Drevets, WC
Khanna, A
Zarate, CA
Furey, ML
AF Szczepanik, Joanna
Nugent, Allison C.
Drevets, Wayne C.
Khanna, Ashish
Zarate, Carlos A., Jr.
Furey, Maura L.
TI Amygdala response to explicit sad face stimuliat baseline predicts
antidepressant treatment response to scopolamine in major depressive
disorder
SO PSYCHIATRY RESEARCH-NEUROIMAGING
LA English
DT Article
DE Major depressive disorder; Amygdala; Rapid-acting antidepressants;
Scopolamine; Stimulus processing; Functional magnetic resonance imaging
(fMRI)
ID EMOTIONAL FACES; MOOD-STATE; PERSONALIZED MEDICINE; SELECTIVE ATTENTION;
FEARFUL FACES; BIOMARKERS; FMRI; SUPERSENSITIVITY; PATHOPHYSIOLOGY;
ACETYLCHOLINE
AB The muscarinic antagonist scopolamine produces rapid antidepressant effects in individuals with major depressive disorder (MDD). In healthy subjects, manipulation of acetyl-cholinergic transmission modulates attention in a stimulus-dependent manner. This study tested the hypothesis that baseline amygdalar activity in response to emotional stimuli correlates with antidepressant treatment response to scopolamine and could thus potentially predict treatment outcome. MDD patients and healthy controls performed an attention shifting task involving emotional faces while undergoing functional magnetic resonance imaging (fMRI). We found that blood oxygenation level dependent (BOLD) signal in the amygdala acquired while MDD patients processed sad face stimuli correlated positively with antidepressant response to scopolamine. Amygdalar response to sad faces in MDD patients who did not respond to scopolamine did not differ from that of healthy controls. This suggests that the pre-treatment task elicited amygdalar activity that may constitute a biomarker of antidepressant treatment response to scopolamine. Furthermore, in MDD patients who responded to scopolamine, we observed a post-scopolamine stimulus processing shift towards a pattern demonstrated by healthy controls, indicating a change in stimulus-dependent neural response potentially driven by attenuated cholinergic activity in the amygdala. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
C1 [Szczepanik, Joanna; Nugent, Allison C.; Zarate, Carlos A., Jr.; Furey, Maura L.] NIMH, Expt Therapeut & Pathophysiol Branch, NIH, Bldg 10 CRC,Rm 7-5565, Bethesda, MD 20892 USA.
[Drevets, Wayne C.] Johnson & Johnson Inc, Janssen Pharmaceut LLC, Titusville, NJ USA.
[Khanna, Ashish] Brooklyn Hosp Ctr, Jewish Med Ctr, Phys Med & Rehabil, Brooklyn, NY USA.
[Furey, Maura L.] Janssen Res & Dev, Neurosci Biomarkers Div, San Diego, CA USA.
RP Szczepanik, J (reprint author), NIMH, Expt Therapeut & Pathophysiol Branch, NIH, Bldg 10 CRC,Rm 7-5565, Bethesda, MD 20892 USA.
EM szczepaj@mail.nih.gov
FU Intramural Research Program at the National Institute of Mental Health;
National Institutes of Health (IRP-NIMH-NIH) [NCT00369915, ZIA
MH002927]; NARSAD Independent Investigator; Brain & Behavior Mood
Disorders Research Award
FX Funding for this work was supported in part by the Intramural Research
Program at the National Institute of Mental Health, National Institutes
of Health (IRP-NIMH-NIH; NCT00369915, ZIA MH002927), by a NARSAD
Independent Investigator to Dr. Zarate, and by a Brain & Behavior Mood
Disorders Research Award to Dr. Zarate. These funding sources had no
further role in study design; in the collection, analysis, or
interpretation of data; in the writing of the report; or in the decision
to submit the paper for publication. Dr. Zarate is listed as a
co-inventor on a patent application for the use of ketamine and its
metabolites in major depression, and Dr. Furey is identified as a
co-inventor on a patent application for the use of scopolamine in mood
disorders. Drs. Zarate and Furey have assigned their rights in these
patents to the U.S. government but will share a percentage of any
royalties that may be received by the government. Dr. Furey was a
full-time employee of the NIMH at the time this study was conducted. All
other authors have no conflict of interest to disclose, financial or
otherwise.
NR 53
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PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0925-4927
EI 1872-7506
J9 PSYCHIAT RES-NEUROIM
JI Psychiatry Res. Neuroimaging
PD AUG 30
PY 2016
VL 254
BP 67
EP 73
DI 10.1016/j.pscychresns.2016.06.005
PG 7
WC Clinical Neurology; Neuroimaging; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA DU6HU
UT WOS:000382316000010
PM 27366831
ER
PT J
AU Cai, XY
Li, HY
Liu, AY
AF Cai, Xiaoyu
Li, Huiyun
Liu, Aiyi
TI A marginal rank-based inverse normal transformation approach to
comparing multiple clinical trial endpoints
SO STATISTICS IN MEDICINE
LA English
DT Article
DE clinical trials; multiple endpoints; power of test; rank-based
transformation; ratio of dependent variables; type I error
ID FUNCTIONAL LINEAR-MODELS; QUANTITATIVE TRAITS; FAMILY; ASSOCIATION;
QUALITY; INDEX
AB The increase in incidence of obesity and chronic diseases and their health care costs have raised the importance of quality diet on the health policy agendas. The healthy eating index is an important measure for diet quality which consists of 12 components derived from ratios of dependent variables with distributions hard to specify, measurement errors and excessive zero observations difficult to model parametrically. Hypothesis testing involving data of such nature poses challenges because the widely used multiple comparison procedures such as Hotelling's T-2 test and Bonferroni correction may suffer from substantial loss of efficiency. We propose a marginal rank-based inverse normal transformation approach to normalizing the marginal distribution of the data before employing a multivariate test procedure. Extensive simulation was conducted to demonstrate the ability of the proposed approach to adequately control the type I error rate as well as increase the power of the test, with data particularly from non-symmetric or heavy-tailed distributions. The methods are exemplified with data from a dietary intervention study for type I diabetic children. Published 2016. This article is a U.S. Government work and is in the public domain in the USA
C1 [Cai, Xiaoyu] George Washington Univ, Dept Stat, Washington, DC 20052 USA.
[Li, Huiyun] Beijing Inst Technol, Sch Management & Econ, Beijing 100081, Peoples R China.
[Liu, Aiyi] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Biostat & Bioinformat Branch, Rockville, MD 20852 USA.
RP Liu, AY (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Biostat & Bioinformat Branch, Rockville, MD 20852 USA.
EM liua@mail.nih.gov
OI Liu, Aiyi/0000-0002-6618-5082
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development Intramural Research Program [HHSN267200703434C,
HHSN2752008000031/HHSN275002]
FX Research of A. Liu was supported by the Eunice Kennedy Shriver National
Institute of Child Health and Human Development Intramural Research
Program (contract #HHSN267200703434C and #HHSN2752008000031/HHSN275002).
The authors thank Drs. Ruzong Fan for helpful discussions and Tonja
Nansel for providing the dietary quality data from the CHEF study. The
authors thank two anonymous referees for their constructive comments
that helped improve the manuscript.
NR 15
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U1 5
U2 7
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 AUG 30
PY 2016
VL 35
IS 19
BP 3259
EP 3271
DI 10.1002/sim.6928
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 DS0YS
UT WOS:000380323400002
PM 26990442
ER
PT J
AU Wu, MX
Shu, Y
Li, ZH
Liu, AY
AF Wu, Mixia
Shu, Yu
Li, Zhaohai
Liu, Aiyi
TI Repeated significance tests of linear combinations of sensitivity and
specificity of a diagnostic biomarker
SO STATISTICS IN MEDICINE
LA English
DT Article
DE expected sample size; inference upon early stopping; sensitivity;
sequential testing; specificity; two-stage designs; type I error;
Youden's index
ID II CLINICAL-TRIALS; SEQUENTIAL EVALUATION; 2-STAGE DESIGNS; ACCURACY;
PREVALENCE; EFFICIENT; BIAS
AB A sequential design is proposed to test whether the accuracy of a binary diagnostic biomarker meets the minimal level of acceptance. The accuracy of a binary diagnostic biomarker is a linear combination of the marker's sensitivity and specificity. The objective of the sequential method is to minimize the maximum expected sample size under the null hypothesis that the marker's accuracy is below the minimal level of acceptance. The exact results of two-stage designs based on Youden's index and efficiency indicate that the maximum expected sample sizes are smaller than the sample sizes of the fixed designs. Exact methods are also developed for estimation, confidence interval and p-value concerning the proposed accuracy index upon termination of the sequential testing. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.
C1 [Wu, Mixia] Beijing Univ Technol, Coll Appl Sci, Beijing 100124, Peoples R China.
[Shu, Yu] Abbott Labs Vasc Div, 3200 Lakeside Dr, Santa Clara, CA 95054 USA.
[Li, Zhaohai] George Washington Univ, Dept Stat, 801 22nd St NW, Washington, DC 20052 USA.
[Liu, Aiyi] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Biostat & Bioinformat Branch, 6100 Execut Blvd, Rockville, MD 20852 USA.
RP Liu, AY (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Biostat & Bioinformat Branch, 6100 Execut Blvd, Rockville, MD 20852 USA.
EM liua@mail.nih.gov
OI Liu, Aiyi/0000-0002-6618-5082
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development (NICHD), National Institutes of Health (NIH)
FX Research of A. Liu is supported by the Intramural Research Program of
the Eunice Kennedy Shriver National Institute of Child Health and Human
Development (NICHD), the National Institutes of Health (NIH). The
authors thank two anonymous referees and an associate editor for their
constructive comments that resulted in an improved manuscript.
NR 31
TC 0
Z9 0
U1 0
U2 1
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 AUG 30
PY 2016
VL 35
IS 19
BP 3397
EP 3412
DI 10.1002/sim.6932
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 DS0YS
UT WOS:000380323400011
PM 26947768
ER
PT J
AU Shaw, PA
Fay, MP
AF Shaw, Pamela A.
Fay, Michael P.
TI A rank test for bivariate time-to-event outcomes when one event is a
surrogate
SO STATISTICS IN MEDICINE
LA English
DT Article
DE bivariate survival; composite outcome; interval censoring;
semi-competing risks; surrogate endpoints; survival analysis
ID INTERVAL-CENSORED-DATA; MULTIPLE END-POINTS; CLINICAL-TRIALS; SURVIVAL;
FAILURE; NPMLE
AB In many clinical settings, improving patient survival is of interest but a practical surrogate, such as time to disease progression, is instead used as a clinical trial's primary endpoint. A time-to-first endpoint (e.g., death or disease progression) is commonly analyzed but may not be adequate to summarize patient outcomes if a subsequent event contains important additional information. We consider a surrogate outcome very generally as one correlated with the true endpoint of interest. Settings of interest include those where the surrogate indicates a beneficial outcome so that the usual time-to-first endpoint of death or surrogate event is nonsensical. We present a new two-sample test for bivariate, interval-censored time-to-event data, where one endpoint is a surrogate for the second, less frequently observed endpoint of true interest. This test examines whether patient groups have equal clinical severity. If the true endpoint rarely occurs, the proposed test acts like a weighted logrank test on the surrogate; if it occurs for most individuals, then our test acts like a weighted logrank test on the true endpoint. If the surrogate is a useful statistical surrogate, our test can have better power than tests based on the surrogate that naively handles the true endpoint. In settings where the surrogate is not valid (treatment affects the surrogate but not the true endpoint), our test incorporates the information regarding the lack of treatment effect from the observed true endpoints and hence is expected to have a dampened treatment effect compared with tests based on the surrogate alone. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.
C1 [Shaw, Pamela A.] Univ Penn, Perelman Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA.
[Fay, Michael P.] NIAID, Biostat Res Branch, Rockville, MD USA.
RP Shaw, PA (reprint author), Univ Penn, Perelman Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA.
EM shawp@upenn.edu
OI Fay, Michael P./0000-0002-8643-9625
FU Intramural NIH HHS [Z99 AI999999]
NR 24
TC 0
Z9 0
U1 1
U2 1
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 AUG 30
PY 2016
VL 35
IS 19
BP 3413
EP 3423
DI 10.1002/sim.6950
PG 11
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 DS0YS
UT WOS:000380323400012
PM 27059817
ER
PT J
AU Brooks, AT
Krumlauf, M
Fryer, CS
Beck, KH
Yang, L
Ramchandani, VA
Wallen, GR
AF Brooks, Alyssa Todaro
Krumlauf, Michael
Fryer, Craig S.
Beck, Kenneth H.
Yang, Li
Ramchandani, Vijay A.
Wallen, Gwenyth R.
TI Critical Transitions: A Mixed Methods Examination of Sleep from
Inpatient Alcohol Rehabilitation Treatment to the Community
SO PLOS ONE
LA English
DT Article
ID QUALITY INDEX; DAYTIME SLEEPINESS; DEPENDENT PATIENTS; INSOMNIA; SCALE;
ABSTINENCE; DRINKING; DURATION; RELAPSE; DEPRESSION
AB Aims
This prospective, repeated measures study utilized a convergent parallel mixed methods approach to assess sleep experiences among individuals who were alcohol-dependent undergoing inpatient detoxification and treatment at a clinical research facility across the transition periods associated with the rehabilitation process: the initial adjustment to becoming an inpatient and the transition from inpatient to outpatient status.
Methods
This study included individual semi-structured interviews and quantitative measures relating to psychological distress, sleep quality, daytime sleepiness, and sleep-related beliefs and behavior (n = 33; 66.7% male). Interviews were conducted and questionnaires were administered within one week of participants' scheduled discharge date and again four to six weeks post-discharge when they returned for a follow-up visit (or via phone).
Results
Participants self-reported significant sleep disturbances at both study time points. Of those participants with valid data at both time points (n = 28), there were no significant changes in mean scores from pre- to post-discharge with the exception of self-efficacy for sleep (SE-S) being significantly higher post-discharge. Preliminary qualitative findings suggested differences between those with ongoing sleep disturbances, those whose sleep disturbances had resolved, and those with no sleep disturbances at either time point.
Conclusions
This analysis highlights individual variation in sleep throughout the process of inpatient treatment and transition to outpatient aftercare in individuals with alcohol dependence. Collecting quantitative and qualitative data concurrently and combining emerging themes from qualitative data with quantitative analyses allowed for a more thorough examination of this relatively novel area of research and provided information that can be utilized to inform future behavioral sleep interventions.
C1 [Brooks, Alyssa Todaro; Krumlauf, Michael; Yang, Li; Wallen, Gwenyth R.] NIH, Ctr Clin, Bethesda, MD 20892 USA.
[Brooks, Alyssa Todaro; Ramchandani, Vijay A.] NIAAA, Bethesda, MD 20892 USA.
[Fryer, Craig S.; Beck, Kenneth H.] Univ Maryland, Sch Publ Hlth, Dept Behav & Community Hlth, College Pk, MD 20742 USA.
RP Brooks, AT (reprint author), NIH, Ctr Clin, Bethesda, MD 20892 USA.; Brooks, AT (reprint author), NIAAA, Bethesda, MD 20892 USA.
EM todaroad@mail.nih.gov; gwallen@cc.nih.gov
FU National Institutes of Health, Clinical Center intramural research
program
FX This project has been funded in whole or in part with federal funds from
the National Institutes of Health, Clinical Center intramural research
program. 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.
NR 49
TC 0
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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 AUG 29
PY 2016
VL 11
IS 8
AR e0161725
DI 10.1371/journal.pone.0161725
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DV4DZ
UT WOS:000382876700030
PM 27571353
ER
PT J
AU Martinez, NJ
Rai, G
Yasgar, A
Lea, WA
Sun, HM
Wang, YH
Luci, DK
Yang, SM
Nishihara, K
Takeda, S
Sagor, M
Earnshaw, I
Okada, T
Mori, K
Wilson, K
Riggins, GJ
Xia, MH
Grimaldi, M
Jadhav, A
Maloney, DJ
Simeonov, A
AF Martinez, Natalia J.
Rai, Ganesha
Yasgar, Adam
Lea, Wendy A.
Sun, Hongmao
Wang, Yuhong
Luci, Diane K.
Yang, Shyh-Ming
Nishihara, Kana
Takeda, Shunichi
Sagor, Mohiuddin
Earnshaw, Irina
Okada, Tetsuya
Mori, Kazutoshi
Wilson, Kelli
Riggins, Gregory J.
Xia, Menghang
Grimaldi, Maurizio
Jadhav, Ajit
Maloney, David J.
Simeonov, Anton
TI A High-Throughput Screen Identifies 2,9-Diazaspiro[5.5]Undecanes as
Inducers of the Endoplasmic Reticulum Stress Response with Cytotoxic
Activity in 3D Glioma Cell Models
SO PLOS ONE
LA English
DT Article
ID UNFOLDED-PROTEIN RESPONSE; ER STRESS; MALIGNANT GLIOMA; DEATH; CA2+;
CANCER; ACTIVATION; GRP78/BIP; AUTOPHAGY; XBP1
AB The endoplasmic reticulum (ER) is involved in Ca2+ signaling and protein folding. ER Ca2+ depletion and accumulation of unfolded proteins activate the molecular chaperone GRP78 (glucose-regulated protein 78) which in turn triggers the ER stress response (ERSR) pathway aimed to restore ER homeostasis. Failure to adapt to stress, however, results in apoptosis. We and others have shown that malignant cells are more susceptible to ERSR-induced apoptosis than their normal counterparts, implicating the ERSR as a potential target for cancer therapeutics. Predicated on these findings, we developed an assay that uses a GRP78 biosensor to identify small molecule activators of ERSR in glioma cells. We performed a quantitative high-throughput screen (qHTS) against a collection of similar to 425,000 compounds and a comprehensive panel of orthogonal secondary assays was formulated for stringent compound validation. We identified novel activators of ERSR, including a compound with a 2,9-diazaspiro[5.5]undecane core, which depletes intracellular Ca2+ stores and induces apoptosis-mediated cell death in several cancer cell lines, including patient-derived and 3D cultures of glioma cells. This study demonstrates that our screening platform enables the identification and profiling of ERSR inducers with cytotoxic activity and advocates for characterization of these compound in in vivo models.
C1 [Martinez, Natalia J.; Rai, Ganesha; Yasgar, Adam; Lea, Wendy A.; Sun, Hongmao; Wang, Yuhong; Luci, Diane K.; Yang, Shyh-Ming; Nishihara, Kana; Wilson, Kelli; Xia, Menghang; Jadhav, Ajit; Maloney, David J.; Simeonov, Anton] NIH, Natl Ctr Adv Translat Sci, Rockville, MD 20850 USA.
[Nishihara, Kana; Sagor, Mohiuddin; Earnshaw, Irina] Kyoto Univ, Grad Sch Med, Dept Radiat Genet, Sakyo Ku, Kyoto 6068501, Japan.
[Okada, Tetsuya; Mori, Kazutoshi] Kyoto Univ, Grad Sch Sci, Dept Biophys, Sakyo Ku, Kyoto 6068502, Japan.
[Takeda, Shunichi; Wilson, Kelli; Riggins, Gregory J.] Johns Hopkins Univ, Dept Neurosurg, Baltimore, MD 21231 USA.
[Grimaldi, Maurizio] Southern Res Inst, Dept Biochem & Mol Biol, Neuropharmacol Lab, Birmingham, AL 35205 USA.
RP Maloney, DJ; Simeonov, A (reprint author), NIH, Natl Ctr Adv Translat Sci, Rockville, MD 20850 USA.
EM maloneyd@mail.nih.gov; asimeono@mail.nih.gov
OI Earnshaw, Irina/0000-0002-9546-6641
FU National Center for Advancing Translational Sciences; Molecular
Libraries Initiative of the National Institutes of Health Roadmap for
Medical Research [U54MH084681, DA031669]
FX NJM, GR, AY, WAL, HS, YW, DKL, SMY, MX, AJ, DJM and AS were supported by
the intramural research program of the National Center for Advancing
Translational Sciences and the Molecular Libraries Initiative of the
National Institutes of Health Roadmap for Medical Research (U54MH084681
and DA031669).
NR 45
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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 AUG 29
PY 2016
VL 11
IS 8
AR e0161486
DI 10.1371/journal.pone.0161486
PG 19
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DV4DZ
UT WOS:000382876700021
PM 27570969
ER
PT J
AU Zhao, WT
Pang, Q
Xu, RX
Liu, JW
Liu, SF
Li, J
Su, XZ
AF Zhao, Wenting
Pang, Qin
Xu, Ruixue
Liu, Jianwen
Liu, Shengfa
Li, Jian
Su, Xin-zhuan
TI Monitoring the Prevalence of Leucocytozoon sabrazesi in Southern China
and Testing Tricyclic Compounds against Gametocytes
SO PLOS ONE
LA English
DT Article
ID AVIAN BLOOD PARASITES; PCR-BASED DETECTION; HAEMOPROTEUS; PLASMODIUM;
INFECTION; CHICKENS; SIMONDI; MALARIA; BIRDS; OWLS
AB Leucocytozoon parasites infect many species of avian hosts, including domestic chicken, and can inflict heavy economic loss on the poultry industry. Two major species of Leucocytozoon parasites have been reported in China, L. sabrazesi and L. caulleryi, although L. sabrazesi appears to be more widespread than L. caulleryi in southern China. The traditional method for detecting Leucocytozoon infection is microscopic examination of blood smears for the presence of mature gametocytes in circulation, which may miss infections with low parasitemia (gametocytemia) or immature gametocytes. Here we developed a PCR-based method to monitor L. sabrazesi infections at seven sites in four provinces of China after testing two PCR primer pairs based on parasite mitochondrial cytochrome b (cytb) and cytochrome c oxidase III (coxIII) genes. We compared the results of PCR detection with those of microscopic observation. As expected, the PCR assays were more sensitive than microscope examination in detecting L. sabrazesi infection and were able to detect parasite DNA after gametocytes disappeared in the blood stream. Using these methods, we investigated monthly dynamics of L. sabrazesi in chickens from a free-range farm in Xiamen, Fujian province of China, over one year. Our results showed that chickens were infected with L. sabrazesi year-round in southern China. Finally, we tested several compounds for potential treatment of Leucocytozoon infections, including primaquine, ketotifen, clomipramine hydrochloride, desipramine hydrochloride, sulfaquinoxaline, and pyrimethamine. Only primaquine had activity against L. sabrazesi gametocytes. Our results provide important information for controlling parasite transmission in southern China and disease management.
C1 [Zhao, Wenting; Pang, Qin; Xu, Ruixue; Liu, Jianwen; Liu, Shengfa; Li, Jian; Su, Xin-zhuan] Xiamen Univ, Sch Life Sci, Innovat Ctr Cell Signaling Network, State Key Lab Cellular Stress Biol, Xiamen 361005, Fujian, Peoples R China.
[Su, Xin-zhuan] NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA.
RP Li, J; Su, XZ (reprint author), Xiamen Univ, Sch Life Sci, Innovat Ctr Cell Signaling Network, State Key Lab Cellular Stress Biol, Xiamen 361005, Fujian, Peoples R China.; Su, XZ (reprint author), NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA.
EM jianli_204@xmu.edu.cn; xsu@niaid.nih.gov
OI Su, Xinzhuan/0000-0003-3246-3248
FU National Natural Science Foundation of China [81220108019, 81271858,
81572017]; Fundamental Research Funds for the Central Universities
[20720160057]; Project 111 of the State Bureau of Foreign Experts and
Ministry of Education of China [B06016]; Division of Intramural
Research, National Institute of Allergy and Infectious Diseases,
National Institutes of Health
FX This work was supported by the National Natural Science Foundation of
China #81220108019, #81271858, and #81572017, by Fundamental Research
Funds for the Central Universities (20720160057), by Project 111 of the
State Bureau of Foreign Experts and Ministry of Education of China
(B06016), and by the Division of Intramural Research, National Institute
of Allergy and Infectious Diseases, National Institutes of Health. The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 42
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U1 4
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 AUG 29
PY 2016
VL 11
IS 8
AR e0161869
DI 10.1371/journal.pone.0161869
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DV4DZ
UT WOS:000382876700038
PM 27571513
ER
PT J
AU Banadyga, L
Dolan, MA
Ebihara, H
AF Banadyga, Logan
Dolan, Michael A.
Ebihara, Hideki
TI Rodent-Adapted Filoviruses and the Molecular Basis of Pathogenesis
SO JOURNAL OF MOLECULAR BIOLOGY
LA English
DT Review
DE Filovirus; Ebola virus; Marburg virus; rodent adaptation; pathogenesis
ID EBOLA-VIRUS VP24; MARBURG HEMORRHAGIC-FEVER; REVERSE GENETICS SYSTEM;
SYRIAN GOLDEN-HAMSTER; VERVET MONKEY DISEASE; MATRIX PROTEIN VP40;
DOUBLE-STRANDED-RNA; OUTBRED GUINEA-PIG; MOUSE MODEL; INTERFERON
ANTAGONISM
AB Ebola, Marburg, and Ravn viruses, all filoviruses, are the causative agents of severe hemorrhagic fever. Much of what we understand about the pathogenesis of filovirus disease is derived from work with animal models, including nonhuman primates, which are considered the "gold standard" filovirus model since they faithfully recapitulate the clinical hallmarks of filovirus disease. However, rodent models, including the mouse, guinea pig, and hamster, also exist for Ebola, Marburg, and Ravn viruses, and although they may not reproduce all the clinical signs of filovirus disease, thanks to their relative ease of use and low cost, they are often the first choice for initial descriptions of virus pathogenesis and evaluation of antiviral prophylactics and therapeutics. Since filoviruses do not cause significant disease in adult, immunocompetent rodents, these models rely on "rodent-adapted" viruses that have been passaged several times through their host until virulence and lethality are achieved. In the process of adaptation, the viruses acquire numerous nucleotide/amino acid mutations that contribute to virulence in their rodent host. Interestingly, virus protein 24 (VP24) and nucleoprotein (NP) appear to be major virulence factors for ebolaviruses in rodents, whereas VP40 appears to be the major virulence factor for marburgviruses. By characterizing these mutations and understanding the molecular mechanisms that lead to the acquisition of virulence, we can gain better insight into the pathogenic processes that underlie filovirus disease in humans. These processes, and the viral and/or cellular proteins that contribute to them, will make attractive targets for the development of novel therapeutics and counter-measures. Published by Elsevier Ltd.
C1 [Banadyga, Logan; Ebihara, Hideki] NIAID, Virol Lab, Div Intramural Res, NIH, Hamilton, MT 59840 USA.
[Dolan, Michael A.] NIAID, Bioinformat & Computat Biosci Branch, NIH, Bethesda, MD 20892 USA.
RP Ebihara, H (reprint author), 903 South 4th St, Hamilton, MT 59840 USA.
EM ebiharah@niaid.nih.gov
FU Division of Intramural Research, NIAID, NIH
FX The authors are grateful to Ryan Kissinger and Austin Athman (Visual
Medical Arts, Rocky Mountain Laboratories) for their technical
assistance in preparing Fig. 2. We thank Heinz Feldmann for his critical
review of this manuscript. The authors are supported by the Division of
Intramural Research, NIAID, NIH. Opinions, interpretations, conclusions,
and recommendations are those of the authors and are not necessarily
endorsed by the NIH.
NR 136
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Z9 3
U1 6
U2 7
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 AUG 28
PY 2016
VL 428
IS 17
SI SI
BP 3449
EP 3466
DI 10.1016/j.jmb.2016.05.008
PG 18
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA DW0FD
UT WOS:000383315400008
PM 27189922
ER
PT J
AU Du, C
Pusey, BN
Adams, CJ
Lau, CC
Bone, WP
Gahl, WA
Markello, TC
Adams, DR
AF Du, Chen
Pusey, Barbara N.
Adams, Christopher J.
Lau, C. Christopher
Bone, William P.
Gahl, William A.
Markello, Thomas C.
Adams, David R.
TI Explorations to improve the completeness of exome sequencing
SO BMC MEDICAL GENOMICS
LA English
DT Article
DE Clinical exome sequencing; Analytical quality; Performance enhancement;
Clinical genomics; Rare diseases; Completeness problem; False negative
results
ID HUMAN PHENOTYPE ONTOLOGY; UNDIAGNOSED DISEASES; HUMAN GENOME; INTRONIC
MUTATION; CLINICAL EXOME; FRAMEWORK; VARIANTS; PROGRAM; POPULATION;
DISCOVERY
AB Background: Exome sequencing has advanced to clinical practice and proven useful for obtaining molecular diagnoses in rare diseases. In approximately 75 % of cases, however, a clinical exome study does not produce a definitive molecular diagnosis. These residual cases comprise a new diagnostic challenge for the genetics community. The Undiagnosed Diseases Program of the National Institutes of Health routinely utilizes exome sequencing for refractory clinical cases. Our preliminary data suggest that disease-causing variants may be missed by current standard-of-care clinical exome analysis. Such false negatives reflect limitations in experimental design, technical performance, and data analysis.
Results: We present examples from our datasets to quantify the analytical performance associated with current practices, and explore strategies to improve the completeness of data analysis. In particular, we focus on patient ascertainment, exome capture, inclusion of intronic variants, and evaluation of medium-sized structural variants.
Conclusions: The strategies we present may recover previously-missed, disease causing variants in second-pass exome analysis. Understanding the limitations of the current clinical exome search space provides a rational basis to improve methods for disease variant detection using genome-scale sequencing techniques.
C1 [Du, Chen; Pusey, Barbara N.; Adams, Christopher J.; Lau, C. Christopher; Bone, William P.; Gahl, William A.; Markello, Thomas C.; Adams, David R.] NHGRI, Undiagnosed Dis Program, Common Fund, NIH, Bethesda, MD 20892 USA.
RP Adams, DR (reprint author), NHGRI, Undiagnosed Dis Program, Common Fund, NIH, Bethesda, MD 20892 USA.
EM dadams1@mail.nih.gov
FU Intramural Research Program of the National Human Genome Research
Institute; Common Fund of the National Institutes of Health
FX This research is supported by the Intramural Research Program of the
National Human Genome Research Institute and the Common Fund of the
National Institutes of Health.
NR 64
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U1 5
U2 5
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1755-8794
J9 BMC MED GENOMICS
JI BMC Med. Genomics
PD AUG 27
PY 2016
VL 9
AR 56
DI 10.1186/s12920-016-0216-3
PG 11
WC Genetics & Heredity
SC Genetics & Heredity
GA DU4XE
UT WOS:000382215400001
PM 27568008
ER
PT J
AU Freedhoff, Y
Hall, KD
AF Freedhoff, Yoni
Hall, Kevin D.
TI Weight loss diet studies: we need help not hype
SO LANCET
LA English
DT Editorial Material
ID RANDOMIZED CONTROLLED-TRIAL; LOW-FAT DIET; METAANALYSIS; ADHERENCE;
OUTCOMES; ADULTS
C1 [Freedhoff, Yoni] Bariatr Med Inst, Ottawa, ON, Canada.
[Hall, Kevin D.] NIDDK, Integrat Physiol Sect, Lab Biol Modeling, Bethesda, MD 20892 USA.
RP Hall, KD (reprint author), NIDDK, Integrat Physiol Sect, Lab Biol Modeling, Bethesda, MD 20892 USA.
EM kevinh@niddk.nih.gov
NR 13
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Z9 2
U1 7
U2 7
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0140-6736
EI 1474-547X
J9 LANCET
JI Lancet
PD AUG 27
PY 2016
VL 388
IS 10047
BP 849
EP 851
PG 3
WC Medicine, General & Internal
SC General & Internal Medicine
GA DU0RI
UT WOS:000381911800008
PM 27597452
ER
PT J
AU Zhao, YP
Zhang, T
Huo, HH
Ye, YH
Liu, YF
AF Zhao, Yupeng
Zhang, Ting
Huo, Huanhuan
Ye, Yihong
Liu, Yanfen
TI Lunapark Is a Component of a Ubiquitin Ligase Complex Localized to the
Endoplasmic Reticulum Three-way Junctions
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
DE endoplasmic-reticulum-associated protein degradation (ERAD); protein
misfolding; ubiquitin; ubiquitin ligase; ubiquitin-conjugating enzyme
(E2 enzyme); Atlastin; ER three-way junction; Lunapark; Lnp; gp78;
misfolded
ID ER-ASSOCIATED DEGRADATION; MEMBRANE-PROTEINS; POLYUBIQUITIN CHAINS;
GP78; REQUIRES; CYTOSOL; GENERATION; MORPHOLOGY; NETWORK; ENZYMES
AB The endoplasmic reticulum (ER) network comprises sheets and tubules that are connected by dynamic three-way junctions. Lunapark (Lnp) localizes to and stabilizes ER three-way junctions by antagonizing the small GTPase Atlastin, but how Lnp shapes the ER network is unclear. Here, we used an affinity purification approach and mass spectrometry to identify Lnp as an interacting partner of the ER protein quality control ubiquitin ligase gp78. Accordingly, Lnp purified from mammalian cells has a ubiquitin ligase activity in vitro. Intriguingly, biochemical analyses show that this activity can be attributed not only to associated ubiquitin ligase, but also to an intrinsic ubiquitin ligase activity borne by Lnp itself. This activity is contained in the N-terminal 45 amino acids of Lnp although this segment does not share homology to any known ubiquitin ligase motifs. Despite its interaction with gp78, Lnp does not seem to have a broad function in degradation of misfolded ER proteins. On the other hand, the N-terminal ubiquitin ligase-bearing motif is required for the ER three-way junction localization of Lnp. Our study identifies a new type of ubiquitin ligase and reveals a potential link between ubiquitin and ER morphology regulation.
C1 [Zhao, Yupeng; Huo, Huanhuan; Liu, Yanfen] ShanghaiTech Univ, Sch Life Sci & Technol, 100 Haike Rd, Shanghai 201210, Peoples R China.
[Zhang, Ting; Ye, Yihong] NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Liu, YF (reprint author), ShanghaiTech Univ, Sch Life Sci & Technol, 100 Haike Rd, Shanghai 201210, Peoples R China.; Ye, YH (reprint author), NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
EM yihongy@mail.nih.gov; liuyf@shanghaitech.edu.cn
FU National Institutes of Health Intramural Research Program NIDDK Grant
[1ZIADK033008-06]; National Natural Science Foundation of China
[31570781]
FX This work was supported, in whole or in part, by National Institutes of
Health Intramural Research Program NIDDK Grant 1ZIADK033008-06 and
National Natural Science Foundation of China Grant 31570781. The authors
declare no conflict 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 48
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U1 3
U2 3
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 AUG 26
PY 2016
VL 291
IS 35
BP 18252
EP 18262
DI 10.1074/jbc.M116.737783
PG 11
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA DV9EC
UT WOS:000383241800018
PM 27387505
ER
PT J
AU Rosas-Hernandez, H
Cuevas, E
Lantz, SM
Rice, KC
Gannon, BM
Fantegrossi, WE
Gonzalez, C
Paule, MG
Ali, SF
AF Rosas-Hernandez, Hector
Cuevas, Elvis
Lantz, Susan M.
Rice, Kenner C.
Gannon, Brenda M.
Fantegrossi, William E.
Gonzalez, Carmen
Paule, Merle G.
Ali, Syed F.
TI Methamphetamine, 3,4-methylenedioxymethamphetamine (MDMA) and
3,4-methylenedioxypyrovalerone (MDPV) induce differential cytotoxic
effects in bovine brain microvessel endothelial cells
SO NEUROSCIENCE LETTERS
LA English
DT Article
DE Methamphetamine; MDMA; MDPV; Blood-brain barrier; Cytotoxicity
ID BARRIER DISRUPTION; OXIDATIVE STRESS; DOPAMINE TRANSPORTER; IN-VITRO;
HYPERTHERMIA; ECSTASY; COCAINE; METHYLENEDIOXYPYROVALERONE;
NEUROINFLAMMATION; VASOCONSTRICTION
AB Designer drugs such as synthetic psychostimulants are indicative of a worldwide problem of drug abuse and addiction. In addition to methamphetamine (METH), these drugs include 3,4-methylenedioxy-methamphetamine (MDMA) and commercial preparations of synthetic cathinones including 3,4-methylenedioxypyrovalerone (MDPV), typically referred to as "bath salts." These psychostimulants exert neurotoxic effects by altering monoamine systems in the brain. Additionally, METH and MDMA adversely affect the integrity of the blood-brain barrier (BBB): there are no current reports on the effects of MDPV on the BBB. The aim of this study was to compare the effects of METH, MDMA and MDPV on bovine brain microvessel endothelial cells (bBMVECs), an accepted in vitro model of the BBB. Confluent bBMVEC monolayers were treated with METH, MDMA and MDPV (0.5 mM-2.5 mM) for 24 h. METH and MDMA increased lactate dehydrogenase release only at the highest concentration (2.5 mM), whereas MDPV induced cytotoxicity at all concentrations. MDMA and METH decreased cellular proliferation only at 2.5 mM, with similar effects observed after MDPV exposures starting at 1 mM. Only MDPV increased reactive oxygen species production at all concentrations tested whereas all 3 drugs increased nitric oxide production. Morphological analysis revealed different patterns of compound-induced cell damage. METH induced vacuole formation at 1 mM and disruption of the monolayer at 2.5 mM. MDMA induced disruption of the endothelial monolayer from 1 mM without vacuolization. On the other hand, MDPV induced monolayer disruption at doses >= 0.5 mM without vacuole formation; at 2.5 mM, the few remaining cells lacked endothelial morphology. These data suggest that even though these synthetic psychostimulants altermonoaminergic systems, they each induce BBB toxicity by different mechanisms with MDPV being the most toxic. Published by Elsevier Ireland Ltd.
C1 [Rosas-Hernandez, Hector; Cuevas, Elvis; Lantz, Susan M.; Paule, Merle G.; Ali, Syed F.] US FDA, Neurochem Lab, Div Neurotoxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA.
[Rice, Kenner C.] NIAAA, Drug Design & Synth Sect, Mol Targets & Medicat Discovery Branch, NIDA, Bethesda, MD USA.
[Gannon, Brenda M.; Fantegrossi, William E.] UAMS, Dept Pharmacol & Toxicol, Little Rock, AR USA.
[Gonzalez, Carmen] UASLP, Fac Ciencias Quim, Slp, Mexico.
RP Ali, SF (reprint author), US FDA, Neurochem Lab, Div Neurotoxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA.
EM Syed.Ali@fda.hhs.gov
FU U.S. Department of Energy; U.S. Food and Drug Administration; Intramural
Research Programs of the National Institute on Drug Abuse; National
Institute on Alcoholism and Alcohol Abuse
FX This research was supported in part by an appointment (H. R-H.) to the
Research Participation Program at the National Center for Toxicological
Research administered by the Oak Ridge Institute for Science and
Education through an interagency agreement between the U.S. Department
of Energy and the U.S. Food and Drug Administration. A portion of this
work was supported by the Intramural Research Programs of the National
Institute on Drug Abuse and the National Institute on Alcoholism and
Alcohol Abuse. The content is solely the responsibility of the authors
and does not necessarily represent the official views of the US. Food
and Drug Administration, the National Institute on Drug Abuse, the
National Institute of Alcohol Abuse and Alcoholism, or the National
Institutes of Health.
NR 45
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PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0304-3940
EI 1872-7972
J9 NEUROSCI LETT
JI Neurosci. Lett.
PD AUG 26
PY 2016
VL 629
BP 125
EP 130
DI 10.1016/j.neulet.2016.06.029
PG 6
WC Neurosciences
SC Neurosciences & Neurology
GA DU7QF
UT WOS:000382409000023
PM 27320055
ER
PT J
AU Dellibovi-Ragheb, TA
AF Dellibovi-Ragheb, Teegan A.
TI Next Gen PhD A Guide to Career Paths in Science
SO SCIENCE
LA English
DT Book Review
C1 [Dellibovi-Ragheb, Teegan A.] NHLBI, NIH, Bldg 10, Bethesda, MD 20892 USA.
RP Dellibovi-Ragheb, TA (reprint author), NHLBI, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM teegan.dellibovi-ragheb@nih.gov
NR 1
TC 0
Z9 0
U1 4
U2 4
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 AUG 26
PY 2016
VL 353
IS 6302
BP 877
EP 877
DI 10.1126/science.aah3463
PG 1
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DU0CA
UT WOS:000381867700023
ER
PT J
AU Sherman, ME
Ichikawa, L
Pfeiffer, RM
Miglioretti, DL
Kerlikowske, K
Tice, J
Vacek, PM
Gierach, GL
AF Sherman, Mark E.
Ichikawa, Laura
Pfeiffer, Ruth M.
Miglioretti, Diana L.
Kerlikowske, Karla
Tice, Jeffery
Vacek, Pamela M.
Gierach, Gretchen L.
TI Relationship of Predicted Risk of Developing Invasive Breast Cancer, as
Assessed with Three Models, and Breast Cancer Mortality among Breast
Cancer Patients
SO PLOS ONE
LA English
DT Article
ID HORMONE-RECEPTOR STATUS; POSTMENOPAUSAL WOMEN; SCREENING-PROGRAM;
MAMMOGRAPHY; VALIDATION; CONSORTIUM; PREVENTION; REDUCTION; PROGNOSIS;
ONCOLOGY
AB Purpose
Breast cancer risk prediction models are used to plan clinical trials and counsel women; however, relationships of predicted risks of breast cancer incidence and prognosis after breast cancer diagnosis are unknown.
Methods
Using largely pre-diagnostic information from the Breast Cancer Surveillance Consortium (BCSC) for 37,939 invasive breast cancers (1996-2007), we estimated 5-year breast cancer risk (< 1%; 1-1.66%; >= 1.67%) with three models: BCSC 1-year risk model (BCSC-1; adapted to 5-year predictions); Breast Cancer Risk Assessment Tool (BCRAT); and BCSC 5-year risk model (BCSC-5). Breast cancer-specific mortality post-diagnosis (range: 1-13 years; median: 5.4-5.6 years) was related to predicted risk of developing breast cancer using unadjusted Cox proportional hazards models, and in age-stratified (35-44; 45-54; 55-69; 70-89 years) models adjusted for continuous age, BCSC registry, calendar period, income, mode of presentation, stage and treatment. Mean age at diagnosis was 60 years.
Results
Of 6,021 deaths, 2,993 (49.7%) were ascribed to breast cancer. In unadjusted case-only analyses, predicted breast cancer risk >= 1.67% versus < 1.0% was associated with lower risk of breast cancer death; BCSC-1: hazard ratio (HR) = 0.82 (95% CI = 0.75-0.90); BCRAT: HR = 0.72 (95% CI = 0.65-0.81) and BCSC-5: HR = 0.84 (95% CI = 0.75-0.94). Age-stratified, adjusted models showed similar, although mostly non-significant HRs. Among women ages 55-69 years, HRs approximated 1.0. Generally, higher predicted risk was inversely related to percentages of cancers with unfavorable prognostic characteristics, especially among women 35-44 years.
Conclusions
Among cases assessed with three models, higher predicted risk of developing breast cancer was not associated with greater risk of breast cancer death; thus, these models would have limited utility in planning studies to evaluate breast cancer mortality reduction strategies. Further, when offering women counseling, it may be useful to note that high predicted risk of developing breast cancer does not imply that if cancer develops it will behave aggressively.
C1 [Sherman, Mark E.] NCI, Canc Prevent Div, Bethesda, MD 20892 USA.
[Sherman, Mark E.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Ichikawa, Laura; Miglioretti, Diana L.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA USA.
[Pfeiffer, Ruth M.; Gierach, Gretchen L.] Div Canc Epidemiol & Genet, Bethesda, MD USA.
[Miglioretti, Diana L.] Univ Calif Davis, Dept Publ Hlth, Davis, CA 95616 USA.
[Kerlikowske, Karla; Tice, Jeffery] Univ Calif San Francisco, Dept Med, San Francisco, CA USA.
[Kerlikowske, Karla] Univ Calif San Francisco, Dept Epidemiol Biostat, San Francisco, CA 94143 USA.
[Vacek, Pamela M.] Univ Vermont, Sch Med, Dept Med Biostat, Burlington, VT 05405 USA.
RP Sherman, ME (reprint author), NCI, Canc Prevent Div, Bethesda, MD 20892 USA.; Sherman, ME (reprint author), NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
EM ShermanM@mail.nih.gov
RI Gierach, Gretchen/E-1817-2016
OI Gierach, Gretchen/0000-0002-0165-5522
FU Intramural Research Program of the National Cancer Institute
[HHSN261201100031C]; several state public health departments and cancer
registries throughout the US
FX This was funded in part by the Intramural Research Program of the
National Cancer Institute (HHSN261201100031C). The collection of cancer
and vital status data used in this study was supported in part by
several state public health departments and cancer registries throughout
the US. For a full description of these sources, please see:
http://breastscreening.cancer.gov/work/acknowledgement.html. The funders
had no role in study design, data collection and analysis, decision to
publish, or preparation of the manuscript.
NR 39
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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 AUG 25
PY 2016
VL 11
IS 8
AR e0160966
DI 10.1371/journal.pone.0160966
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DU5NN
UT WOS:000382258600021
PM 27560501
ER
PT J
AU Lo, B
Fritz, JM
Su, HC
Uzel, G
Jordan, MB
Lenardo, MJ
AF Lo, Bernice
Fritz, Jill M.
Su, Helen C.
Uzel, Gulbu
Jordan, Michael B.
Lenardo, Michael J.
TI CHAI and LATAIE: new genetic diseases of CTLA-4 checkpoint insufficiency
SO BLOOD
LA English
DT Article
ID REGULATORY T-CELLS; IMMUNE DYSREGULATION; LRBA MUTATION;
RHEUMATOID-ARTHRITIS; FOLLICULAR HELPER; DEFICIENCY; RESPONSES; PATIENT;
HYDROXYCHLOROQUINE; TRANSPLANTATION
AB CTLA-4 is a critical inhibitory "checkpoint" molecule of immune activation. Several recent reports have described patients with immune dysregulation and lymphoproliferative disease resulting from 2 different genetic diseases that directly or indirectly cause CTLA-4 deficiency. Numerous articles have also been published describing CTLA-4 blockade in cancer immunotherapy and its side effects, which are ultimately the consequence of treatment-induced CTLA-4 deficiency. Here, we review these 2 diseases and CTLA-4 blockade therapy, emphasizing the crucial role of CTLA-4 in immune checkpoint regulation.
C1 [Lo, Bernice] Sidra Med & Res Ctr, Div Translat Med, POB 26999, Doha, Qatar.
[Lo, Bernice; Fritz, Jill M.; Lenardo, Michael J.] NIAID, Mol Dev, Immune Syst Sect, Immunol Lab,NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Lo, Bernice; Fritz, Jill M.; Su, Helen C.; Lenardo, Michael J.] NIAID, Clin Genom Program, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Su, Helen C.] NIAID, Human Immunol Dis Sect, Lab Host Defenses, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Uzel, Gulbu] NIAID, Lab Clin Infect Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Jordan, Michael B.] Univ Cincinnati, Dept Pediat, Div Bone Marrow Transplantat & Immune Deficiency, Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH USA.
[Jordan, Michael B.] Univ Cincinnati, Div Immunobiol, Dept Pediat, Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH USA.
RP Lo, B (reprint author), Sidra Med & Res Ctr, Div Translat Med, POB 26999, Doha, Qatar.; Lenardo, MJ (reprint author), Immunol Lab, 10 Ctr Dr,Bldg 10,Room 11D14, Bethesda, MD 20892 USA.
EM blo@sidra.org; lenardo@nih.gov
OI Lo, Bernice/0000-0002-1087-6845
FU Intramural Research Program of the National Institute of Allergy and
Infectious Diseases, National Institutes of Health
FX This work was supported by the Intramural Research Program of the
National Institute of Allergy and Infectious Diseases, National
Institutes of Health.
NR 48
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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 AUG 25
PY 2016
VL 128
IS 8
BP 1037
EP 1042
DI 10.1182/blood-2016-04-712612
PG 6
WC Hematology
SC Hematology
GA DW7LT
UT WOS:000383832900010
PM 27418640
ER
PT J
AU Alvarnas, JC
Le Rademacher, J
Wang, YL
Little, RF
Akpek, G
Ayala, E
Devine, S
Baiocchi, R
Lozanski, G
Kaplan, L
Noy, A
Popat, U
Hsu, J
Morris, LE
Thompson, J
Horowitz, MM
Mendizabal, A
Levine, A
Krishnan, A
Forman, SJ
Navarro, WH
Ambinder, R
AF Alvarnas, Joseph C.
Le Rademacher, Jennifer
Wang, Yanli
Little, Richard F.
Akpek, Gorgun
Ayala, Ernesto
Devine, Steven
Baiocchi, Robert
Lozanski, Gerard
Kaplan, Lawrence
Noy, Ariela
Popat, Uday
Hsu, Jack
Morris, Lawrence E., Jr.
Thompson, Jason
Horowitz, Mary M.
Mendizabal, Adam
Levine, Alexandra
Krishnan, Amrita
Forman, Stephen J.
Navarro, Willis H.
Ambinder, Richard
TI Autologous hematopoietic cell transplantation for HIV-related lymphoma:
results of the BMT CTN 0803/AMC 071 trial
SO BLOOD
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; HIGH-DOSE THERAPY; ACTIVE ANTIRETROVIRAL
THERAPY; AIDS-RELATED LYMPHOMA; NON-HODGKINS-LYMPHOMA;
PROGNOSTIC-FACTORS; SALVAGE TREATMENT; INFECTION; DISEASE; CHEMOTHERAPY
AB Autologous hematopoietic cell transplant (AHCT) for HIV-infected patients is largely limited to centers with HIV-specific expertise. The Blood and Marrow Transplant Clinical Trials Network 0803/AIDS Malignancy Consortium 071 trial is a multicenter phase 2 study of AHCT for patients with HIV-related lymphoma (HRL). Eligible patients had chemotherapy-sensitive relapsed/persistent HRL, were >15 years of age, and had treatable HIV infection. Patients were prepared using carmustine, etoposide, cytarabine, and melphalan and received consistent management of peritransplant antiretroviral treatment. The primary endpoint was 1-year overall survival. Forty-three patients were enrolled; 40 underwent AHCT. Pretransplant HIV viral load was undetectable (<50 copies/mL) in 32 patients (80%); the median CD4 count was 249/mu L (range, 39-797). At a median follow-up of 24.8 months, 1-year and 2-year overall survival probabilities were 87.3% (95% confidence interval [CI], 72.1-94.5) and82%(95% CI, 65.9-91), respectively. The probability of 2-year progression-free survival was 79.8% (95% CI, 63.7-89.4). One-year transplant-related mortality was 5.2%. Median time to neutrophil and platelet recovery was 11 days and 18 days, respectively. Nine patients experienced a total of 13 unexpected grade 3-5 adverse events posttransplant (10 grade 3 and 3 grade 4 events). Twenty-two patients had at least 1 infectious episode posttransplant. At 1 year post-AHCT, median CD4(+) T-cell count was 280.3 (range, 28.8-1148.0); 82.6% had an undetectable HIV viral load. Trial patients were compared with 151 matched Center for International Bone Marrow Transplant Research controls. Outcomes between HIV-infected patients and controls were not statistically significantly different. HRL patients should be considered candidates for AHCT if they meet standard transplant criteria. The trial was registered at www.clinicaltrials.gov as #NCT01141712.
C1 [Alvarnas, Joseph C.; Krishnan, Amrita; Forman, Stephen J.] City Hope Natl Med Ctr, Dept Hematol Hematopoiet Cell Transplantat, 1500 E Duarte Rd, Duarte, CA 91010 USA.
[Le Rademacher, Jennifer; Horowitz, Mary M.] Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA.
[Wang, Yanli; Thompson, Jason; Mendizabal, Adam] Emmes Corp, Rockville, MD USA.
[Little, Richard F.] NCI, Canc Therapy Evaluat Program, Rockville, MD USA.
[Akpek, Gorgun] Univ Maryland Med Syst, Greenebaum Canc Ctr, Baltimore, MD USA.
[Ayala, Ernesto] H Lee Moffitt Canc Ctr & Res Inst, Dept Blood & Marrow Transplantat, Tampa, FL USA.
[Devine, Steven; Baiocchi, Robert; Lozanski, Gerard] Ohio State Univ, Arthur G James Canc Ctr Hosp, Dept Hematol, Columbus, OH 43210 USA.
[Kaplan, Lawrence] Univ Calif San Francisco, Div Hematol Oncol, San Francisco, CA 94143 USA.
[Noy, Ariela] Mem Sloan Kettering Canc Ctr, Div Hematol Oncol, 1275 York Ave, New York, NY 10021 USA.
[Popat, Uday] Univ Texas MD Anderson Canc Ctr, Dept Stem Cell Transplantat & Cellular Therapy, Houston, TX 77030 USA.
[Hsu, Jack] Univ Florida, Hlth Canc Ctr, Bone Marrow Transplant Program, Gainesville, FL USA.
[Morris, Lawrence E., Jr.] Northside Hosp Canc Inst, Blood & Marrow Transplant Grp Georgia, Atlanta, GA USA.
[Levine, Alexandra] City Hope Natl Med Ctr, 1500 E Duarte Rd,MOB3001, Duarte, CA 91010 USA.
[Navarro, Willis H.] Natl Marrow Donor Program, Minneapolis, MN USA.
[Ambinder, Richard] Johns Hopkins Sch Med, Dept Oncol, Baltimore, MD USA.
RP Alvarnas, JC (reprint author), City Hope Natl Med Ctr, 1500 E Duarte Rd,MOB3001, Duarte, CA 91010 USA.
EM jalvarnas@coh.org
FU National Institutes of Health National Cancer Institute (NCI)
[HHSN21200622012C-009]; AMC through NCI [U01CA121947]; National Heart,
Lung, and Blood Institute; NCI [U10HL069294]
FX This work is supported by grants from the National Institutes of Health
National Cancer Institute (NCI; grant HHSN21200622012C-009) and the AMC
through NCI (grant U01CA121947). The Blood and Marrow Transplant
Clinical Trials Network infrastructure is supported in part by the
National Heart, Lung, and Blood Institute and NCI (grant U10HL069294).
NR 41
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PI WASHINGTON
PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA
SN 0006-4971
EI 1528-0020
J9 BLOOD
JI Blood
PD AUG 25
PY 2016
VL 128
IS 8
BP 1050
EP 1058
DI 10.1182/blood-2015-08-664706
PG 9
WC Hematology
SC Hematology
GA DW7LT
UT WOS:000383832900012
PM 27297790
ER
PT J
AU Schmidt, J
Gong, SY
Marafioti, T
Mankel, B
Gonzalez-Farre, B
Balague, O
Mozos, A
Cabecadas, J
van der Walt, J
Hoehn, D
Rosenwald, A
Ott, G
Dojcinov, S
Egan, C
Nadeu, F
Ramis-Zaldivar, JE
Clot, G
Barcena, C
Perez-Alonso, V
Endris, V
Penzel, R
Lome-Maldonado, C
Bonzheim, I
Fend, F
Campo, E
Jaffe, ES
Salaverria, I
Quintanilla-Martinez, L
AF Schmidt, Janine
Gong, Shunyou
Marafioti, Teresa
Mankel, Barbara
Gonzalez-Farre, Blanca
Balague, Olga
Mozos, Ana
Cabecadas, Jose
van der Walt, Jon
Hoehn, Daniela
Rosenwald, Andreas
Ott, German
Dojcinov, Stefan
Egan, Caoimhe
Nadeu, Ferran
Ramis-Zaldivar, Joan Enric
Clot, Guillem
Barcena, Carmen
Perez-Alonso, Vanesa
Endris, Volker
Penzel, Roland
Lome-Maldonado, Carmen
Bonzheim, Irina
Fend, Falko
Campo, Elias
Jaffe, Elaine S.
Salaverria, Itziar
Quintanilla-Martinez, Leticia
TI Genome-wide analysis of pediatric-type follicular lymphoma reveals low
genetic complexity and recurrent alterations of TNFRSF14 gene
SO BLOOD
LA English
DT Article
ID LYMPHOCYTIC-LEUKEMIA; CLINICAL-FEATURES; NODULAR LYMPHOMA; YOUNG-ADULTS;
MUTATIONS; EXPRESSION; CHILDREN; RECEPTOR; BTLA; TRANSLOCATION
AB Pediatric-type follicular lymphoma (PTFL) is a variant of follicular lymphoma (FL) with distinctive clinicopathological features. Patients are predominantly young males presenting with localized lymphadenopathy; the tumor shows high-grade cytology and lacks both BCL2 expression and t(14; 18) translocation. The genetic alterations involved in the pathogenesis of PTFL are unknown. Therefore, 42 PTFL (40 males and 2 females; mean age, 16 years; range, 5-31) were genetically characterized. For comparison, 11 cases of conventional t(14: 18)(-) FL in adults were investigated. Morphologically, PTFL cases had follicular growth pattern without diffuse areas and characteristic immunophenotype. All cases showed monoclonal immunoglobulin (IG) rearrangement. PTFL displays low genomic complexity when compared with t(14; 18)(-) FL (mean, 0.77 vs 9 copy number alterations per case; P <.001). Both groups presented 1p36 alterations including TNFRSF14, but copy-number neutral loss of heterozygosity (CNN-LOH) of this locus was more frequently observed in PTFL (40% vs 9%; P =.075). TNFRSF14 was the most frequently affected gene in PTFL (21 mutations and 2 deletions), identified in 54% of cases, followed by KMT2D mutations in 16%. Other histone-modifying genes were rarely affected. In contrast, t(14; 18)(-) FL displayed a mutational profile similar to t(14; 18)(+) FL. In 8 PTFL cases (19%), no genetic alterations were identified beyond IG monoclonal rearrangement. The genetic landscape of PTFL suggests that TNFRSF14 mutations accompanied by CNN-LOH of the 1p36 locus in over 70% of mutated cases, as additional selection mechanism, might play a key role in the pathogenesis of this disease. The genetic profiles of PTFL and t(14; 18)(-) FL in adults indicate that these are two different disorders.
C1 [Schmidt, Janine; Mankel, Barbara; Bonzheim, Irina; Fend, Falko; Quintanilla-Martinez, Leticia] Univ Tubingen, Inst Pathol & Neuropathol, Tubingen, Germany.
[Schmidt, Janine; Mankel, Barbara; Bonzheim, Irina; Fend, Falko; Quintanilla-Martinez, Leticia] Univ Hosp Tubingen, Ctr Comprehens Canc, Tubingen, Germany.
[Gong, Shunyou; Egan, Caoimhe; Jaffe, Elaine S.] NCI, Hematopathol Sect, Pathol Lab, Bethesda, MD 20892 USA.
[Marafioti, Teresa] Barts & London NHS Trust, Dept Cellular Pathol, London, England.
[Gonzalez-Farre, Blanca; Balague, Olga; Nadeu, Ferran; Ramis-Zaldivar, Joan Enric; Clot, Guillem; Campo, Elias; Salaverria, Itziar] Hosp Clin Barcelona, Hematopathol Unit, Inst Invest Biomed August Pi & Sunyer, Barcelona, Spain.
[Mozos, Ana] Hosp Santa Creu & Sant Pau, Dept Pathol, Barcelona, Spain.
[Cabecadas, Jose] Inst Portugues Oncol Francisco Gentil, Dept Pathol, Lisbon, Portugal.
[van der Walt, Jon] Guys & St Thomas Hosp, Dept Histopathol, London, England.
[Hoehn, Daniela] Columbia Univ, Dept Pathol & Cell Biol, Med Ctr, New York, NY USA.
[Rosenwald, Andreas] Univ Wurzburg, Inst Pathol, Wurzburg, Germany.
[Rosenwald, Andreas] Comprehens Canc Ctr Mainfranken, Wurzburg, Germany.
[Ott, German] Robert Bosch Krankenhaus, Dept Clin Pathol, Stuttgart, Germany.
[Ott, German] Dr Margarete Fischer Bosch Inst Clin Pharmacol, Stuttgart, Germany.
[Dojcinov, Stefan] Univ Wales Hosp, Dept Pathol, All Wales Lymphoma Panel, Cardiff, S Glam, Wales.
[Barcena, Carmen; Perez-Alonso, Vanesa] Hosp Univ 12 Octubre, Madrid, Spain.
[Endris, Volker; Penzel, Roland] Univ Heidelberg Hosp, Inst Pathol, Heidelberg, Germany.
[Lome-Maldonado, Carmen] Inst Nacl Cancerol, Dept Pathol, Mexico City, DF, Mexico.
RP Quintanilla-Martinez, L (reprint author), Univ Tubingen, Inst Pathol, Univ Hosp Tubingen, Liebermeisterstr 8, D-72076 Tubingen, Germany.; Quintanilla-Martinez, L (reprint author), Ctr Comprehens Canc, Liebermeisterstr 8, D-72076 Tubingen, Germany.; Salaverria, I (reprint author), IDIBAPS, Rossello 153, Barcelona 08036, Spain.
EM isalaver@clinic.ub.es; leticia.quintanilla-fend@med.uni-tuebingen.de
RI Campo, elias/O-7192-2016;
OI Campo, elias/0000-0001-9850-9793; Cabecadas, Jose/0000-0001-6232-1596
FU Fondo de Investigaciones Sanitarias; Instituto de Salud Carlos III
(Miguel Servet) [CP13/00159, PI15/00580]; Generalitat de Catalunya
Suport Grups de Recerca [2013-SGR-378]; European Regional Development
Fund "Una manera de fer Europa"; Wilhelm-Sander-Stiftung [2015.058.1]
FX This work was supported by Fondo de Investigaciones Sanitarias,
Instituto de Salud Carlos III (Miguel Servet contract CP13/00159 and
PI15/00580), Generalitat de Catalunya Suport Grups de Recerca
(2013-SGR-378), the European Regional Development Fund "Una manera de
fer Europa" and the Wilhelm-Sander-Stiftung (2015.058.1; L.Q.-M. and
F.F.). This work was partially developed at the Centro Esther Koplowitz,
Barcelona, Spain.
NR 41
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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 AUG 25
PY 2016
VL 128
IS 8
BP 1101
EP 1111
DI 10.1182/blood-2016-03-703819
PG 11
WC Hematology
SC Hematology
GA DW7LT
UT WOS:000383832900018
PM 27257180
ER
PT J
AU Gopich, IV
Szabo, A
AF Gopich, Irina V.
Szabo, Attila
TI Reversible Stochastically Gated Diffusion-Influenced Reactions
SO JOURNAL OF PHYSICAL CHEMISTRY B
LA English
DT Article
ID ASSOCIATION-DISSOCIATION REACTION; DEPENDENT RATE COEFFICIENTS;
MICHAELIS-MENTEN KINETICS; INTEGRAL ENCOUNTER THEORY; MANY-PARTICLE
TREATMENT; LONG-TIME ASYMPTOTICS; BIMOLECULAR REACTIONS; MULTISTAGE
REACTIONS; LIQUID SOLUTIONS; REACTION-RATES
AB An approximate but accurate theory is developed for the kinetics of reversible binding of a ligand to a macromolecule when either can stochastically fluctuate between reactive and unreactive conformations. The theory is based on a set of reaction-diffusion equations for the deviations of the pair distributions from their bulk values. The concentrations are shown to satisfy non-Markovian rate equations with memory kernels that are obtained by solving an irreversible geminate (i.e., two-particle) problem. The relaxation to equilibrium is not exponential but rather a power law. In the Markovian limit, the theory reduces to a set of ordinary rate equations with renormalized rate constants.
C1 [Gopich, Irina V.; Szabo, Attila] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
RP Szabo, A (reprint author), NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
EM attilas@niddk.nih.gov
RI Szabo, Attila/H-3867-2012
FU Intramural Research Program of the National Institute of Diabetes and
Digestive and Kidney Diseases (NIDDK), National Institutes of Health
FX This work was supported by the Intramural Research Program of the
National Institute of Diabetes and Digestive and Kidney Diseases
(NIDDK), National Institutes of Health.
NR 53
TC 1
Z9 1
U1 4
U2 4
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1520-6106
J9 J PHYS CHEM B
JI J. Phys. Chem. B
PD AUG 25
PY 2016
VL 120
IS 33
BP 8080
EP 8089
DI 10.1021/acs.jpcb.6b00152
PG 10
WC Chemistry, Physical
SC Chemistry
GA DU4JZ
UT WOS:000382180200004
PM 26956646
ER
PT J
AU Zhang, X
Xiao, WX
Acencio, ML
Lemke, N
Wang, XJ
AF Zhang, Xue
Xiao, Wangxin
Acencio, Marcio Luis
Lemke, Ney
Wang, Xujing
TI An ensemble framework for identifying essential proteins
SO BMC BIOINFORMATICS
LA English
DT Article
DE Essential protein; Protein-protein interaction networks; Centrality
measure; Ensemble learning; Gene expression
ID SACCHAROMYCES-CEREVISIAE GENOME; ESSENTIAL GENE IDENTIFICATION;
INTERACTION NETWORKS; PPI NETWORK; CENTRALITY; YEAST; DATABASE;
INTEGRATION; EXPRESSION; DISCOVERY
AB Background: Many centrality measures have been proposed to mine and characterize the correlations between network topological properties and protein essentiality. However, most of them show limited prediction accuracy, and the number of common predicted essential proteins by different methods is very small.
Results: In this paper, an ensemble framework is proposed which integrates gene expression data and protein-protein interaction networks (PINs). It aims to improve the prediction accuracy of basic centrality measures. The idea behind this ensemble framework is that different protein-protein interactions (PPIs) may show different contributions to protein essentiality. Five standard centrality measures (degree centrality, betweenness centrality, closeness centrality, eigenvector centrality, and subgraph centrality) are integrated into the ensemble framework respectively. We evaluated the performance of the proposed ensemble framework using yeast PINs and gene expression data. The results show that it can considerably improve the prediction accuracy of the five centrality measures individually. It can also remarkably increase the number of common predicted essential proteins among those predicted by each centrality measure individually and enable each centrality measure to find more low-degree essential proteins.
Conclusions: This paper demonstrates that it is valuable to differentiate the contributions of different PPIs for identifying essential proteins based on network topological characteristics. The proposed ensemble framework is a successful paradigm to this end.
C1 [Zhang, Xue; Wang, Xujing] NHLBI, Syst Biol Core, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Xiao, Wangxin] XiangNan Univ, Dept Comp Sci, Eastern Wangxian Pk, Chenzhou 423000, Hunan, Peoples R China.
[Acencio, Marcio Luis; Lemke, Ney] UNESP Sao Paulo State Univ, Dept Phys & Biophys, Inst Biosci Botucatu, BR-18618970 Botucatu, SP, Brazil.
[Acencio, Marcio Luis] Norwegian Univ Sci & Technol NTNU, Dept Canc Res & Mol Med, PB 8905, N-7491 Trondheim, Norway.
RP Wang, XJ (reprint author), NHLBI, Syst Biol Core, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.; Xiao, WX (reprint author), XiangNan Univ, Dept Comp Sci, Eastern Wangxian Pk, Chenzhou 423000, Hunan, Peoples R China.
EM xiaozhangdoctor@126.com; xujing.wang@nih.gov
RI Acencio, Marcio/D-9264-2012
OI Acencio, Marcio/0000-0002-8278-240X
FU Intramural Research Program of the NIH, NHLBI; National Natural Science
Foundation of China [61402423, 51378243, 61502343]
FX This work was partially supported by the Intramural Research Program of
the NIH, NHLBI; the National Natural Science Foundation of China under
Grants No.61402423, No.51378243, and No. 61502343.
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 1471-2105
J9 BMC BIOINFORMATICS
JI BMC Bioinformatics
PD AUG 25
PY 2016
VL 17
AR 322
DI 10.1186/s12859-016-1166-7
PG 17
WC Biochemical Research Methods; Biotechnology & Applied Microbiology;
Mathematical & Computational Biology
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Mathematical & Computational Biology
GA DV3OJ
UT WOS:000382831900001
ER
PT J
AU Freed, EO
AF Freed, Eric O.
TI Getting IN on Viral RNA Condensation and Virion Maturation
SO CELL
LA English
DT Editorial Material
ID HIV-1 INTEGRASE
AB The retroviral enzyme integrase plays an essential role in the virus replication cycle by catalyzing the covalent insertion of newly synthesized viral DNA into the host cell chromosome early after infection. Now, Kessl et al. report a second function of integrase: binding to the viral RNA genome in virion particles late in the virus replication cycle to promote particle maturation.
C1 [Freed, Eric O.] NCI, Virus Cell Interact Sect, HIV Dynam & Replicat Program, Ctr Canc Res, Frederick, MD 21702 USA.
RP Freed, EO (reprint author), NCI, Virus Cell Interact Sect, HIV Dynam & Replicat Program, Ctr Canc Res, Frederick, MD 21702 USA.
EM efreed@nih.gov
NR 10
TC 0
Z9 0
U1 10
U2 14
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 AUG 25
PY 2016
VL 166
IS 5
BP 1082
EP 1083
DI 10.1016/j.cell.2016.08.013
PG 2
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA DU5NW
UT WOS:000382259500008
PM 27565339
ER
PT J
AU Clever, D
Roychoudhuri, R
Constantinides, MG
Askenase, MH
Sukumar, M
Klebanoff, CA
Eil, RL
Hickman, HD
Yu, ZY
Pan, JH
Palmer, DC
Phan, AT
Goulding, J
Gattinoni, L
Goldrath, AW
Belkaid, Y
Restifo, NP
AF Clever, David
Roychoudhuri, Rahul
Constantinides, Michael G.
Askenase, Michael H.
Sukumar, Madhusudhanan
Klebanoff, Christopher A.
Eil, Robert L.
Hickman, Heather D.
Yu, Zhiya
Pan, Jenny H.
Palmer, Douglas C.
Phan, Anthony T.
Goulding, John
Gattinoni, Luca
Goldrath, Ananda W.
Belkaid, Yasmine
Restifo, Nicholas P.
TI Oxygen Sensing by T Cells Establishes an Immunologically Tolerant
Metastatic Niche
SO CELL
LA English
DT Article
ID HYPOXIA-INDUCIBLE FACTOR-1-ALPHA; TRANSCRIPTION FACTOR;
RESPIRATORY-TRACT; DENDRITIC CELLS; REG-CELLS; PROLYL HYDROXYLATION;
METABOLIC CHECKPOINT; EXPRESSION; DIFFERENTIATION; INFLAMMATION
AB Cancer cells must evade immune responses at distant sites to establish metastases. The lung is a frequent site for metastasis. We hypothesized that lung-specific immunoregulatory mechanisms create an immunologically permissive environment for tumor colonization. We found that T-cell-intrinsic expression of the oxygen-sensing prolyl-hydroxylase (PHD) proteins is required to maintain local tolerance against innocuous antigens in the lung but powerfully licenses colonization by circulating tumor cells. PHD proteins limit pulmonary type helper (Th)-1 responses, promote CD4(+)-regulatory T (Treg) cell induction, and restrain CD8(+) T cell effector function. Tumor colonization is accompanied by PHD-protein-dependent induction of pulmonary Treg cells and suppression of IFN-g-dependent tumor clearance. T-cell-intrinsic deletion or pharmacological inhibition of PHD proteins limits tumor colonization of the lung and improves the efficacy of adoptive cell transfer immunotherapy. Collectively, PHD proteins function in T cells to coordinate distinct immunoregulatory programs within the lung that are permissive to cancer metastasis.
C1 [Clever, David; Roychoudhuri, Rahul; Sukumar, Madhusudhanan; Klebanoff, Christopher A.; Eil, Robert L.; Yu, Zhiya; Pan, Jenny H.; Palmer, Douglas C.; Restifo, Nicholas P.] NCI, Surg Branch, NIH, Bethesda, MD 20892 USA.
[Clever, David] Ohio State Univ, Coll Med, Med Scientist Training Program, Columbus, OH 43210 USA.
[Roychoudhuri, Rahul] Babraham Inst, Lab Lymphocyte Signaling & Dev, Cambridge CB22 3AT, England.
[Constantinides, Michael G.; Askenase, Michael H.; Belkaid, Yasmine] NIAID, Mucosal Immunol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
[Belkaid, Yasmine] NIAID, NIAID Microbiome Program Initiat, NIH, Bethesda, MD 20892 USA.
[Klebanoff, Christopher A.] Mem Sloan Kettering Canc Ctr, Ctr Cell Engn, New York, NY 10065 USA.
[Klebanoff, Christopher A.] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10065 USA.
[Hickman, Heather D.] NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA.
[Phan, Anthony T.; Goulding, John; Goldrath, Ananda W.] Univ Calif San Diego, Div Biol Sci, La Jolla, CA 92093 USA.
[Gattinoni, Luca] NCI, Expt Transplantat Immunol Branch, NIH, Bethesda, MD 20892 USA.
[Restifo, Nicholas P.] NCI, Ctr Cell Based Therapy, NIH, Bethesda, MD 20892 USA.
RP Clever, D; Restifo, NP (reprint author), NCI, Surg Branch, NIH, Bethesda, MD 20892 USA.; Clever, D (reprint author), Ohio State Univ, Coll Med, Med Scientist Training Program, Columbus, OH 43210 USA.; Restifo, NP (reprint author), NCI, Ctr Cell Based Therapy, NIH, Bethesda, MD 20892 USA.
EM david.clever@osumc.edu; restifo@nih.gov
RI Gattinoni, Luca/A-2281-2008; Roychoudhuri, Rahul/A-7442-2010
OI Gattinoni, Luca/0000-0003-2239-3282; Roychoudhuri,
Rahul/0000-0002-5392-1853
FU NCI; NIAID; Wellcome Trust/Royal Society [105663/Z/14/Z]; UK
Biotechnology and Biological Sciences Research Council [BB/N007794/1];
Cancer Research Institute
FX This research was supported by the Intramural Research Programs of the
NCI and NIAID and by charitable gifts from Li Jinyuan and the Tiens
Charitable Foundation and the Milstein Family Foundation. R.R. was
supported by the Wellcome Trust/Royal Society (grant 105663/Z/14/Z) and
the UK Biotechnology and Biological Sciences Research Council (grant
BB/N007794/1). M.G.C. is a Cancer Research Institute Irvington Fellow
supported by the Cancer Research Institute. We thank G.H. Fong for
providing Egln1-3fl/fl mice, D. Haines for pathologic
analysis of H&E-stained tissues, R. Johnson, A. Palazon, and P. Tyrakis
for technical advice.
NR 50
TC 9
Z9 9
U1 27
U2 28
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 AUG 25
PY 2016
VL 166
IS 5
BP 1117
EP +
DI 10.1016/j.cell.2016.07.032
PG 29
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA DU5NW
UT WOS:000382259500011
PM 27565342
ER
PT J
AU Ryan, JF
Schnitzler, CE
Tamm, SL
AF Ryan, Joseph F.
Schnitzler, Christine E.
Tamm, Sidney L.
TI Meeting report of Ctenopalooza: the first international meeting of
ctenophorologists
SO EVODEVO
LA English
DT Article
DE Ctenophora; Ctenophore; Ctenopalooza
ID MNEMIOPSIS-LEIDYI; CTENOPHORES; FERTILIZATION; INVASION; ANIMALS;
SYSTEMS; SUCCESS; ORIGIN
AB Here we present a report on Ctenopalooza: A meeting of ctenophorologists held at the Whitney Laboratory for Marine Bioscience in St. Augustine, FL, USA, on March 14-15, 2016. In this report, we provide a summary of each of the sessions that occurred during this two-day meeting, which touched on most of the relevant areas of ctenophore biology. The report includes some major themes regarding the future of ctenophore research that emerged during Ctenopalooza. More information can be found at the meeting Web site: http://ctenopalooza.whitney.ufl.edu.
C1 [Ryan, Joseph F.; Schnitzler, Christine E.] Univ Florida, Whitney Lab Marine Biosci, St Augustine, FL 32080 USA.
[Ryan, Joseph F.; Schnitzler, Christine E.] Univ Florida, Dept Biol, Gainesville, FL 32611 USA.
[Schnitzler, Christine E.] NHGRI, NIH, Bethesda, MD 20892 USA.
[Tamm, Sidney L.] Marine Biol Lab, Bell Ctr, Woods Hole, MA 02543 USA.
RP Ryan, JF (reprint author), Univ Florida, Whitney Lab Marine Biosci, St Augustine, FL 32080 USA.
EM joseph.ryan@whitney.ufl.edu
FU National Science Foundation's Division of Integrative Organismal Systems
[1619712]; University of Florida's Office of Research to Joseph Ryan
[00075235]; Whitney Laboratory for Marine Bioscience
FX Ctenopalooza was sponsored by a grant from the National Science
Foundation's Division of Integrative Organismal Systems to Joseph Ryan
(#1619712). We also acknowledge funding was provided by a grant from the
University of Florida's Office of Research to Joseph Ryan (Project
#00075235). Additional funding was provided by The Whitney Laboratory
for Marine Bioscience. Student and Postdoc prizes were provided by
Harvard University Press. EvoDevo generously waived open-access fees for
this report.
NR 41
TC 0
Z9 0
U1 5
U2 5
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 2041-9139
J9 EVODEVO
JI EvoDevo
PD AUG 25
PY 2016
VL 7
AR 19
DI 10.1186/s13227-016-0057-3
PG 6
WC Evolutionary Biology; Developmental Biology
SC Evolutionary Biology; Developmental Biology
GA DU7ZV
UT WOS:000382434000001
ER
PT J
AU Kumar, V
Bonifazi, A
Ellenberger, MP
Keck, TM
Pommier, E
Rais, R
Slusher, BS
Gardner, E
You, ZB
Xi, ZX
Newman, AH
AF Kumar, Vivek
Bonifazi, Alessandro
Ellenberger, Michael P.
Keck, Thomas M.
Pommier, Elie
Rais, Rana
Slusher, Barbara S.
Gardner, Eliot
You, Zhi-Bing
Xi, Zheng-Xiong
Newman, Amy Hauck
TI Highly Selective Dopamine D-3 Receptor (D3R) Antagonists and Partial
Agonists Based on Eticlopride and the D3R Crystal Structure: New Leads
for Opioid Dependence Treatment
SO JOURNAL OF MEDICINAL CHEMISTRY
LA English
DT Article
ID CONDITIONED PLACE PREFERENCE; FUNCTIONALIZED LINKING CHAINS; KNOCKOUT
MICE; BEHAVIORAL SENSITIZATION; HIGH-AFFINITY; ADDICTION; COCAINE; RATS;
DISCOVERY; POTENT
AB The recent and precipitous increase in opioid analgesic abuse and overdose has inspired investigation of the dopamine D-3 receptor (D3R) as a target for therapeutic intervention. Metabolic instability or predicted toxicity has precluded successful translation of previously reported D3R-selective antagonists to clinical use for cocaine abuse. Herein, we report a series of novel and D3R crystal structure-guided 4-phenylpiperazines with exceptionally high D3R affinities and/or selectivities with varying efficacies. Lead compound 19 was selected based on its in vitro profile: D3R K-i= 6.84 nM, 1700-fold D3R versus D2R binding selectivity, and its metabolic stability in mouse microsomes. Compound 19 inhibited oxycodone-induced hyperlocomotion in mice and reduced oxycodone-induced locomotor sensitization. In addition, pretreatment with 19 also dose-dependently inhibited the acquisition of oxycodone-induced conditioned place preference (CPP) in rats. These findings support the D3R as a target for opioid dependence treatment and compound 19 as a new lead molecule for development.
C1 [Kumar, Vivek; Bonifazi, Alessandro; Ellenberger, Michael P.; Keck, Thomas M.; Pommier, Elie; Gardner, Eliot; You, Zhi-Bing; Xi, Zheng-Xiong; Newman, Amy Hauck] NIDA, Mol Targets & Medicat Discovery Branch, Intramural Res Program, NIH, 333 Cassell Dr, Baltimore, MD 21224 USA.
[Keck, Thomas M.] Rowan Univ, Coll Sci & Math, Dept Biomed & Translat Sci, Dept Chem & Biochem, 201 Mullica Hill Rd, Glassboro, NJ 08028 USA.
[Pommier, Elie; Rais, Rana; Slusher, Barbara S.] Johns Hopkins Univ, Sch Med, Johns Hopkins Drug Discovery, Dept Neurol, 855 North Wolfe St, Baltimore, MD 21205 USA.
RP Newman, AH (reprint author), NIDA, Mol Targets & Medicat Discovery Branch, Intramural Res Program, NIH, 333 Cassell Dr, Baltimore, MD 21224 USA.
EM anewman@intra.nida.nih.gov
FU National Institute on Drug Abuse - Intramural Research Program; NIDA
Addiction Treatment Discovery Program [ADA151001]; Oregon Health &
Science University; Johns Hopkins Drug Discovery [P30MH075673]
FX Support for this research was provided by the National Institute on Drug
Abuse - Intramural Research Program, NIDA Addiction Treatment Discovery
Program contract (ADA151001) with Oregon Health & Science University and
Johns Hopkins Drug Discovery (P30MH075673 to BSS). We thank Dr.
Anerbasha Shaik for help with the TOC Graphic.
NR 56
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Z9 2
U1 3
U2 3
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 AUG 25
PY 2016
VL 59
IS 16
BP 7634
EP 7650
DI 10.1021/acs.jmedchem.6b00860
PG 17
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA DU4JP
UT WOS:000382179200020
PM 27508895
ER
PT J
AU Huynh, L
Kusnadi, A
Park, SH
Murata, K
Park-Min, KH
Ivashkiv, LB
AF Huynh, Linda
Kusnadi, Anthony
Park, Sung Ho
Murata, Koichi
Park-Min, Kyung-Hyun
Ivashkiv, Lionel B.
TI Opposing regulation of the late phase TNF response by mTORC1-IL-10
signaling and hypoxia in human macrophages
SO SCIENTIFIC REPORTS
LA English
DT Article
ID TUMOR-NECROSIS-FACTOR; INNATE IMMUNE-RESPONSES; RHEUMATOID-ARTHRITIS;
GENE-EXPRESSION; LISTERIA-MONOCYTOGENES; METABOLIC CHECKPOINT; IL-10
PRODUCTION; CUTTING EDGE; I INTERFERON; MICE LACKING
AB Tumor necrosis factor (TNF) is best known for inducing a rapid but transient NF-kappa B-mediated inflammatory response. We investigated later phases of TNF signaling, after the initial transient induction of inflammatory genes has subsided, in primary human macrophages. TNF signaling induced expression of late response genes, including inhibitors of NF-kappa B and TLR signaling, with delayed and sustained kinetics 6-24 hr after TNF stimulation. A subset of late phase genes was expressed in rheumatoid arthritis synovial macrophages, confirming their expression under chronic inflammatory conditions in vivo. Expression of a subset of late phase genes was mediated by autocrine IL-10, which activated STAT3 with delayed kinetics. Hypoxia, which occurs at sites of infection or inflammation where TNF is expressed, suppressed this IL-10-STAT3 autocrine loop and expression of late phase genes. TNF-induced expression of IL-10 and downstream genes was also dependent on signaling by mTORC1, which senses the metabolic state of cells and is modulated by hypoxia. These results reveal an mTORC1-dependent IL-10- mediated late phase response to TNF by primary human macrophages, and identify suppression of IL-10 responses as a new mechanism by which hypoxia can promote inflammation. Thus, hypoxic and metabolic pathways may modulate TNF responses during chronic inflammation.
C1 [Huynh, Linda; Kusnadi, Anthony; Ivashkiv, Lionel B.] Weill Cornell Grad Sch Med Sci, Grad Program Immunol & Microbial Pathogenesis, 1300 York Ave, New York, NY 10021 USA.
[Huynh, Linda; Kusnadi, Anthony; Park, Sung Ho; Murata, Koichi; Park-Min, Kyung-Hyun; Ivashkiv, Lionel B.] Hosp Special Surg, Arthrit & Tissue Degenerat Program, 535 East 70th St, New York, NY 10021 USA.
[Huynh, Linda; Kusnadi, Anthony; Park, Sung Ho; Murata, Koichi; Park-Min, Kyung-Hyun; Ivashkiv, Lionel B.] Hosp Special Surg, David Z Rosensweig Genom Res Ctr, 535 East 70th St, New York, NY 10021 USA.
[Huynh, Linda] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, 31 Ctr Dr,Bldg 31, Bethesda, MD 20892 USA.
RP Ivashkiv, LB (reprint author), Weill Cornell Grad Sch Med Sci, Grad Program Immunol & Microbial Pathogenesis, 1300 York Ave, New York, NY 10021 USA.; Ivashkiv, LB (reprint author), Hosp Special Surg, Arthrit & Tissue Degenerat Program, 535 East 70th St, New York, NY 10021 USA.; Ivashkiv, LB (reprint author), Hosp Special Surg, David Z Rosensweig Genom Res Ctr, 535 East 70th St, New York, NY 10021 USA.
EM ivashkivl@hss.edu
FU NIH [T32 AI007621]
FX We thank Carl Nathan and Amy Cunningham Bussel for access to tissue
culture incubators in which oxygen tension can be regulated. We also
thank Rachael Gordon for pilot experiments showing IL-10 production
downstream of TNF signaling, and Galina Grigoriev and Angela Lee for
processing samples from RA synovial fluids. We thank Laura Donlin for
helpful discussions and critical reading of the manuscript. This work
was supported by grants from the NIH (to L.B.I.). L.H. was supported by
the NIH Grant T32 AI007621 (to the Graduate Program in Immunology and
Microbial Pathogenesis, Weill Cornell Graduate School of Medical
Sciences).
NR 68
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Z9 1
U1 1
U2 1
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 AUG 25
PY 2016
VL 6
AR 31959
DI 10.1038/srep31959
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DU0KI
UT WOS:000381891900001
PM 27558590
ER
PT J
AU Kim, MK
Caplen, N
Chakka, S
Hernandez, L
House, C
Pongas, G
Jordan, E
Annunziata, CM
AF Kim, Marianne K.
Caplen, Natasha
Chakka, Sirisha
Hernandez, Lidia
House, Carrie
Pongas, Georgios
Jordan, Elizabeth
Annunziata, Christina M.
TI Identification of therapeutic targets applicable to clinical strategies
in ovarian cancer
SO BMC CANCER
LA English
DT Article
DE Ovarian cancer; PLK1; MAP3K7/TAK1; WEE1
ID GYNECOLOGIC-ONCOLOGY-GROUP; CARCINOMA; CELLS; ACTIVATION; INHIBITOR;
SURVIVAL; CD133
AB Background: shRNA-mediated lethality screening is a useful tool to identify essential targets in cancer biology. Ovarian cancer (OC) is extremely heterogeneous and most cases are advanced stages at diagnosis. OC has a high response rate initially, but becomes resistant to standard chemotherapy. We previously employed high throughput global shRNA sensitization screens to identify NF-kB related pathways. Here, we re-analyzed our previous shRNA screens in an unbiased manner to identify clinically applicable molecular targets.
Methods: We proceeded with siRNA lethality screening using the top 55 genes in an expanded set of 6 OC cell lines. We investigated clinical relevance of candidate targets in The Cancer Genome Atlas OC dataset. To move these findings towards the clinic, we chose four pharmacological inhibitors to recapitulate the top siRNA effects: Oxozeaenol (for MAP3K7/TAK1), BI6727 (PLK1), MK1775 (WEE1), and Lapatinib (ERBB2). Cytotoxic effects were measured by cellular viability assay, as single agents and in 2-way combinations. Co-treatments were evaluated in either sequential or simultaneous exposure to drug for short term and extended periods to simulate different treatment strategies.
Results: Loss-of-function shRNA screens followed by short-term siRNA validation screens identified therapeutic targets in OC cells. Candidate genes were dysregulated in a subset of TCGA OCs although the alterations of these genes showed no statistical significance to overall survival. Pharmacological inhibitors such as Oxozeaenol, BI6727, and MK1775 showed cytotoxic effects in OC cells regardless of cisplatin responsiveness, while all OC cells tested were cytostatic to Lapatinib. Co-treatment with BI6727 and MK1775 at sub-lethal concentrations was equally potent to BI6727 alone at lethal concentrations without cellular re-growth after the drugs were washed off, suggesting the co-inhibition at reduced dosages may be more efficacious than maximal single-agent cytotoxic concentrations.
Conclusions: Loss-of-function screen followed by in vitro target validation using chemical inhibitors identified clinically relevant targets. This approach has the potential to systematically refine therapeutic strategies in OC. These molecular target-driven strategies may provide additional therapeutic options for women whose tumors have become refractory to standard chemotherapy.
C1 [Kim, Marianne K.; Hernandez, Lidia; House, Carrie; Pongas, Georgios; Jordan, Elizabeth; Annunziata, Christina M.] NCI, Womens Malignancies Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Caplen, Natasha; Chakka, Sirisha] NCI, Gene Silencing Sect, Genet Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Annunziata, Christina M.] Natl Canc Inst, Womens Malignancies Branch, Ctr Canc Res, 10 Ctr Dr,Room 4B54, Bethesda, MD 20892 USA.
RP Annunziata, CM (reprint author), NCI, Womens Malignancies Branch, Ctr Canc Res, Bethesda, MD 20892 USA.; Annunziata, CM (reprint author), Natl Canc Inst, Womens Malignancies Branch, Ctr Canc Res, 10 Ctr Dr,Room 4B54, Bethesda, MD 20892 USA.
EM annunzic@mail.nih.gov
OI Annunziata, Christina/0000-0003-2033-6532
FU Foundation of Women's cancer-Amgen Ovarian Cancer Research Grant;
Intramural Research Program of the National Cancer Institute
FX This work was supported by the Foundation of Women's cancer-Amgen
Ovarian Cancer Research Grant (MK) and the Intramural Research Program
of the National Cancer Institute (CMA).
NR 21
TC 0
Z9 0
U1 2
U2 2
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 AUG 24
PY 2016
VL 16
AR 678
DI 10.1186/s12885-016-2675-5
PG 13
WC Oncology
SC Oncology
GA DX2JR
UT WOS:000384195500001
PM 27558154
ER
PT J
AU Antignani, A
Griner, LM
Guha, R
Simon, N
Pasetto, M
Keller, J
Huang, M
Angelus, E
Pastan, I
Ferrer, M
FitzGerald, DJ
Thomas, CJ
AF Antignani, Antonella
Griner, Lesley Mathews
Guha, Rajarshi
Simon, Nathan
Pasetto, Matteo
Keller, Jonathan
Huang, Manjie
Angelus, Evan
Pastan, Ira
Ferrer, Marc
FitzGerald, David J.
Thomas, Craig J.
TI Chemical Screens Identify Drugs that Enhance or Mitigate Cellular
Responses to Antibody-Toxin Fusion Proteins
SO PLOS ONE
LA English
DT Article
ID PHASE-I TRIAL; IMMUNOTOXIN RFB4(DSFV)-PE38 BL22; ADP-RIBOSYLATING
TOXINS; ANTIMESOTHELIN IMMUNOTOXIN; PSEUDOMONAS EXOTOXIN; CANCER-CELLS;
CLINICAL-EXPERIENCE; BREAST-CANCER; SS1P; COMBINATION
AB The intersection of small molecular weight drugs and antibody-based therapeutics is rarely studied in large scale. Both types of agents are currently part of the cancer armamentarium. However, very little is known about how to combine them in optimal ways. Immunotoxins are antibody-toxin gene fusion proteins engineered to target cancer cells via antibody binding to surface antigens. For fusion proteins derived from Pseudomonas exotoxin (PE), potency relies on the enzymatic domain of the toxin which catalyzes the ADP-ribosylation of EF2 causing inhibition of protein synthesis leading to cell death. Candidate immunotoxins have demonstrated clear value in clinical trials but generally have not been curative as single agents. Therefore we undertook three screens to discover effective combinations that could act synergistically. From the MIPE-3 library of compounds we identified various enhancers of immunotoxin action and at least one major class of inhibitor. Follow-up experiments confirmed the screening data and suggested that immunotoxins when administered with everolimus or nilotinib exhibit favorable combinatory activity and would be candidates for preclinical development. Mechanistic studies revealed that everolimus-immunotoxin combinations acted synergistically on elements of the protein synthetic machinery, including S61 kinase and 4E-BP1 of the mTORC1 pathway. Conversely, PARP inhibitors antagonized immunotoxins and also blocked the toxicity due to native ADP-ribosylating toxins. Thus, our goal of investigating a chemical library was justified based on the identification of several approved compounds that could be developed preclinically as 'enhancers' and at least one class of mitigator to be avoided.
C1 [Antignani, Antonella; Simon, Nathan; Pasetto, Matteo; Huang, Manjie; Angelus, Evan; Pastan, Ira; FitzGerald, David J.] NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bldg 37, Bethesda, MD 20892 USA.
[Griner, Lesley Mathews; Guha, Rajarshi; Keller, Jonathan; Ferrer, Marc; Thomas, Craig J.] NIH, Div Preclin Innovat, Natl Ctr Adv Translat Sci, Rockville, MD 20850 USA.
[Pasetto, Matteo] Univ Verona, Dept Pathol, Verona, Italy.
RP FitzGerald, DJ (reprint author), NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bldg 37, Bethesda, MD 20892 USA.; Thomas, CJ (reprint author), NIH, Div Preclin Innovat, Natl Ctr Adv Translat Sci, Rockville, MD 20850 USA.
EM fitzgerd@helix.nih.gov; craigt@mail.nih.gov
FU National Cancer Institute; National Center for Advancing Translational
Sciences
FX This work was funded by the intramural programs of the National Cancer
Institute and the National Center for Advancing Translational Sciences.
There are no grant or award numbers as the funding is "in-house".
NR 38
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 AUG 24
PY 2016
VL 11
IS 8
AR e0161415
DI 10.1371/journal.pone.0161415
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DU5NI
UT WOS:000382258100040
PM 27556570
ER
PT J
AU Horne, HN
Chung, CC
Zhang, H
Yu, K
Prokunina-Olsson, L
Michailidou, K
Bolla, MK
Wang, Q
Dennis, J
Hopper, JL
Southey, MC
Schmidt, MK
Broeks, A
Muir, K
Lophatananon, A
Fasching, PA
Beckmann, MW
Fletcher, O
Johnson, N
Sawyer, EJ
Tomlinson, I
Burwinkel, B
Marme, F
Guenel, P
Truong, T
Bojesen, SE
Flyger, H
Benitez, J
Gonzalez-Neira, A
Anton-Culver, H
Neuhausen, SL
Brenner, H
Arndt, V
Meindl, A
Schmutzler, RK
Brauch, H
Hamann, U
Nevanlinna, H
Khan, S
Matsuo, K
Iwata, H
Dork, T
Bogdanova, NV
Lindblom, A
Margolin, S
Mannermaa, A
Kosma, VM
Chenevix-Trench, G
Wu, AH
den Berg, DV
Smeets, A
Zhao, H
Chang-Claude, J
Rudolph, A
Radice, P
Barile, M
Couch, FJ
Vachon, C
Giles, GG
Milne, RL
Haiman, CA
Le Marchand, L
Goldberg, MS
Teo, SH
Taib, NAM
Kristensen, V
Borresen-Dale, AL
Zheng, W
Shrubsole, M
Winqvist, R
Jukkola-Vuorinen, A
Andrulis, IL
Knight, JA
Devilee, P
Seynaeve, C
Garcia-Closas, M
Czene, K
Darabi, H
Hollestelle, A
Martens, JWM
Li, JM
Lu, W
Shu, XO
Cox, A
Cross, SS
Blot, W
Cai, QY
Shah, M
Luccarini, C
Baynes, C
Harrington, P
Kang, D
Choi, JY
Hartman, M
Chia, KS
Kabisch, M
Torres, D
Jakubowska, A
Lubinski, J
Sangrajrang, S
Brennan, P
Slager, S
Yannoukakos, D
Shen, CY
Hou, MF
Swerdlow, A
Orr, N
Simard, J
Hall, P
Pharoah, PDP
Easton, DF
Chanock, SJ
Dunning, AM
Figueroa, JD
AF Horne, Hisani N.
Chung, Charles C.
Zhang, Han
Yu, Kai
Prokunina-Olsson, Ludmila
Michailidou, Kyriaki
Bolla, Manjeet K.
Wang, Qin
Dennis, Joe
Hopper, John L.
Southey, Melissa C.
Schmidt, Marjanka K.
Broeks, Annegien
Muir, Kenneth
Lophatananon, Artitaya
Fasching, Peter A.
Beckmann, Matthias W.
Fletcher, Olivia
Johnson, Nichola
Sawyer, Elinor J.
Tomlinson, Ian
Burwinkel, Barbara
Marme, Frederik
Guenel, Pascal
Truong, Therese
Bojesen, Stig E.
Flyger, Henrik
Benitez, Javier
Gonzalez-Neira, Anna
Anton-Culver, Hoda
Neuhausen, Susan L.
Brenner, Hermann
Arndt, Volker
Meindl, Alfons
Schmutzler, Rita K.
Brauch, Hiltrud
Hamann, Ute
Nevanlinna, Heli
Khan, Sofia
Matsuo, Keitaro
Iwata, Hiroji
Dork, Thilo
Bogdanova, Natalia V.
Lindblom, Annika
Margolin, Sara
Mannermaa, Arto
Kosma, Veli-Matti
Chenevix-Trench, Georgia
Wu, Anna H.
den Berg, David Ven
Smeets, Ann
Zhao, Hui
Chang-Claude, Jenny
Rudolph, Anja
Radice, Paolo
Barile, Monica
Couch, Fergus J.
Vachon, Celine
Giles, Graham G.
Milne, Roger L.
Haiman, Christopher A.
Le Marchand, Loic
Goldberg, Mark S.
Teo, Soo H.
Taib, Nur A. M.
Kristensen, Vessela
Borresen-Dale, Anne-Lise
Zheng, Wei
Shrubsole, Martha
Winqvist, Robert
Jukkola-Vuorinen, Arja
Andrulis, Irene L.
Knight, Julia A.
Devilee, Peter
Seynaeve, Caroline
Garcia-Closas, Montserrat
Czene, Kamila
Darabi, Hatef
Hollestelle, Antoinette
Martens, John W. M.
Li, Jingmei
Lu, Wei
Shu, Xiao-Ou
Cox, Angela
Cross, Simon S.
Blot, William
Cai, Qiuyin
Shah, Mitul
Luccarini, Craig
Baynes, Caroline
Harrington, Patricia
Kang, Daehee
Choi, Ji-Yeob
Hartman, Mikael
Chia, Kee Seng
Kabisch, Maria
Torres, Diana
Jakubowska, Anna
Lubinski, Jan
Sangrajrang, Suleeporn
Brennan, Paul
Slager, Susan
Yannoukakos, Drakoulis
Shen, Chen-Yang
Hou, Ming-Feng
Swerdlow, Anthony
Orr, Nick
Simard, Jacques
Hall, Per
Pharoah, Paul D. P.
Easton, Douglas F.
Chanock, Stephen J.
Dunning, Alison M.
Figueroa, Jonine D.
CA kConFab AOCS Investigators
TI Fine-Mapping of the 1p11.2 Breast Cancer Susceptibility Locus
SO PLOS ONE
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; COMMON VARIANTS; CONFER SUSCEPTIBILITY;
GENETIC-VARIATION; 14Q24.1 RAD51L1; RISK; HETEROGENEITY; ALLELES;
DISEASE
AB The Cancer Genetic Markers of Susceptibility genome-wide association study (GWAS) originally identified a single nucleotide polymorphism (SNP) rs11249433 at 1p11.2 associated with breast cancer risk. To fine-map this locus, we genotyped 92 SNPs in a 900kb region (120,505,799-121,481,132) flanking rs11249433 in 45,276 breast cancer cases and 48,998 controls of European, Asian and African ancestry from 50 studies in the Breast Cancer Association Consortium. Genotyping was done using iCOGS, a custom-built array. Due to the complicated nature of the region on chr1p11.2: 120,300,000-120,505,798, that lies near the centromere and contains seven duplicated genomic segments, we restricted analyses to 429 SNPs excluding the duplicated regions (42 genotyped and 387 imputed). Perallelic associations with breast cancer risk were estimated using logistic regression models adjusting for study and ancestry-specific principal components. The strongest association observed was with the original identified index SNP rs11249433 (minor allele frequency (MAF) 0.402; per-allele odds ratio (OR) = 1.10, 95% confidence interval (CI) 1.08-1.13, P = 1.49 x 10(-21)). The association for rs11249433 was limited to ER-positive breast cancers (test for heterogeneity P <= 8.41 x 10(-5)). Additional analyses by other tumor characteristics showed stronger associations with moderately/well differentiated tumors and tumors of lobular histology. Although no significant eQTL associations were observed, in silico analyses showed that rs11249433 was located in a region that is likely a weak enhancer/promoter. Fine-mapping analysis of the 1p11.2 breast cancer susceptibility locus confirms this region to be limited to risk to cancers that are ER-positive.
C1 [Horne, Hisani N.; Chung, Charles C.; Zhang, Han; Yu, Kai; Prokunina-Olsson, Ludmila; Garcia-Closas, Montserrat; Chanock, Stephen J.; Figueroa, Jonine D.] NCI, Div Canc Epidemiol & Genet, Rockville, MD USA.
[Horne, Hisani N.] US FDA, Silver Spring, MD USA.
[Michailidou, Kyriaki; Bolla, Manjeet K.; Wang, Qin; Dennis, Joe; Pharoah, Paul D. P.; Easton, Douglas F.] Univ Cambridge, Ctr Canc Genet Epidemiol, Dept Publ Hlth & Primary Care, Cambridge, England.
[Hopper, John L.; Giles, Graham G.; Milne, Roger L.] Univ Melbourne, Ctr Epidemiol & Biostat, Sch Populat & Global Hlth, Melbourne, Vic, Australia.
[Southey, Melissa C.] Univ Melbourne, Dept Pathol, Melbourne, Vic, Australia.
[Schmidt, Marjanka K.; Broeks, Annegien] Antoni van Leeuwenhoek Hosp, Netherlands Canc Inst, Amsterdam, Netherlands.
[Muir, Kenneth; Lophatananon, Artitaya] Univ Warwick, Div Hlth Sci, Warwick Med Sch, Coventry, W Midlands, England.
[Muir, Kenneth] Univ Manchester, Inst Populat Hlth, Manchester, Lancs, England.
[Fasching, Peter A.; Beckmann, Matthias W.] Univ Erlangen Nurnberg, Dept Obstet & Gynaecol, Univ Hosp Erlangen, Comprehens Canc Ctr Erlangen EMN, Erlangen, Germany.
[Fasching, Peter A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Hematol & Oncol, Los Angeles, CA 90095 USA.
[Fletcher, Olivia; Johnson, Nichola; Orr, Nick] Inst Canc Res, Breakthrough Breast Canc Res Ctr, London, England.
[Fletcher, Olivia; Johnson, Nichola; Swerdlow, Anthony] Inst Canc Res, Div Breast Canc Res, London, England.
[Sawyer, Elinor J.] Kings Coll London, Res Oncol, Guys Hosp, London, England.
[Tomlinson, Ian] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.
[Tomlinson, Ian] Univ Oxford, Oxford Biomed Res Ctr, Oxford, England.
[Burwinkel, Barbara; Marme, Frederik] Heidelberg Univ, Dept Obstet & Gynecol, Heidelberg, Germany.
[Burwinkel, Barbara] German Canc Res Ctr, Mol Epidemiol Grp, Heidelberg, Germany.
[Marme, Frederik] Heidelberg Univ, Natl Ctr Tumor Dis, Heidelberg, Germany.
[Guenel, Pascal; Truong, Therese] INSERM, Environm Epidemiol Canc, Ctr Res Epidemiol & Populat Hlth, Villejuif, France.
[Guenel, Pascal; Truong, Therese] Univ Paris 11, Villejuif, France.
[Bojesen, Stig E.] Copenhagen Univ Hosp, Copenhagen Gen Populat Study, Herlev Hosp, Herlev, Denmark.
[Bojesen, Stig E.] Copenhagen Univ Hosp, Dept Clin Biochem, Herlev Hosp, Herlev, Denmark.
[Bojesen, Stig E.] Univ Copenhagen, Fac Hlth & Med Sci, Copenhagen, Denmark.
[Flyger, Henrik] Copenhagen Univ Hosp, Dept Breast Surg, Herlev Hosp, Herlev, Denmark.
[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.
[Anton-Culver, Hoda] Univ Calif Irvine, Dept Epidemiol, Irvine, CA USA.
[Neuhausen, Susan L.] Beckman Res Inst City Hope, Duarte, CA USA.
[Brenner, Hermann; Arndt, Volker] German Canc Res Ctr, Div Clin Epidemiol & Aging Res, Heidelberg, Germany.
[Brenner, Hermann] German Canc Res Ctr, Div Prevent Oncol, Heidelberg, Germany.
[Brenner, Hermann; Brauch, Hiltrud] German Canc Res Ctr, German Canc Consortium DKTK, Heidelberg, Germany.
[Meindl, Alfons] Tech Univ Munich, Div Gynaecol & Obstet, Munich, Germany.
[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.
[Brauch, Hiltrud] Dr Margarete Fischer Bosch Institute Clin Pharmac, Stuttgart, Germany.
[Brauch, Hiltrud] Univ Tubingen, Tubingen, Germany.
[Hamann, Ute; Kabisch, Maria; Torres, Diana] German Canc Res Ctr, Mol Genet Breast Canc, Heidelberg, Germany.
[Nevanlinna, Heli; Khan, Sofia] Univ Helsinki, Helsinki Univ Hosp, Dept Obstet & Gynecol, Helsinki, Finland.
[Matsuo, Keitaro] Kyushu Univ, Dept Prevent Med, Fac Med Sci, Fukuoka, Japan.
[Iwata, Hiroji] Aichi Canc Ctr Hosp, Dept Breast Oncol, Nagoya, Aichi, Japan.
[Dork, Thilo] Hannover Med Sch, Gynaecol Res Unit, Hannover, Germany.
[Bogdanova, Natalia V.] Hannover Med Sch, Dept Radiat Oncol, Hannover, Germany.
[Lindblom, Annika] Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden.
[Margolin, Sara] Karolinska Inst, Dept Oncol Pathol, Stockholm, Sweden.
[Mannermaa, Arto; Kosma, Veli-Matti] Kuopio Univ Hosp, Ctr Canc, Kuopio, Finland.
[Mannermaa, Arto; Kosma, Veli-Matti] Univ Eastern Finland, Inst Clin Med Pathol & Forens Med, Kuopio, Finland.
[Mannermaa, Arto; Kosma, Veli-Matti] Kuopio Univ Hosp, Imaging Ctr, Dept Clin Pathol, Kuopio, Finland.
[Chenevix-Trench, Georgia] QIMR Berghofer Med Res Inst, Dept Genet, Brisbane, Qld, Australia.
[kConFab AOCS Investigators] Univ Melbourne, Peter MacCallum Canc Ctr, Melbourne, Vic, Australia.
[Wu, Anna H.; den Berg, David Ven; Haiman, Christopher A.] Univ Southern Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA USA.
[Smeets, Ann] Univ Hosp Gashuisberg, Leuven, Belgium.
[Zhao, Hui] Vesalius Res Ctr, Leuven, Belgium.
[Zhao, Hui] Univ Leuven, Lab Translat Genet, Dept Oncol, Leuven, Belgium.
[Chang-Claude, Jenny; Rudolph, Anja] German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany.
[Chang-Claude, Jenny] Univ Med Ctr Hamburg Eppendorf, UCCH, Hamburg, Germany.
[Radice, Paolo] Ist Nazl Tumori, Unit Mol Bases Genet Risk & Genet Testing, Dept Prevent & Predict Med, Fdn IRCCS Ist Ricovero & Cura Carattere Sci, Milan, Italy.
[Barile, Monica] Ist Europeo Oncol, Div Canc Prevent & Genet, Milan, Italy.
[Couch, Fergus J.] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA.
[Vachon, Celine; Slager, Susan] Mayo Clin, Dept Hlth Sci Res, Rochester, MN USA.
[Giles, Graham G.; Milne, Roger L.] Canc Council Victoria, Canc Epidemiol Ctr, Melbourne, Vic, Australia.
[Le Marchand, Loic] Univ Hawaii, Ctr Canc, Honolulu, HI 96822 USA.
[Goldberg, Mark S.] McGill Univ, Dept Med, Montreal, PQ, Canada.
[Goldberg, Mark S.] McGill Univ, Div Clin Epidemiol, Royal Victoria Hosp, Montreal, PQ, Canada.
[Teo, Soo H.] Canc Res Initiat Fdn, Subang Jaya, Selangor, Malaysia.
[Teo, Soo H.; Taib, Nur A. M.] Univ Malaya, Med Ctr, Breast Canc Res Unit, Canc Res Inst, Kuala Lumpur, Malaysia.
[Kristensen, Vessela; Borresen-Dale, Anne-Lise] Oslo Univ Hosp, Dept Genet, Inst Canc Res, Radiumhosp, Oslo, Norway.
[Kristensen, Vessela; Borresen-Dale, Anne-Lise] Univ Oslo, Inst Clin Med, Fac Med, Oslo, Norway.
[Kristensen, Vessela] Univ Oslo, Oslo Univ Hosp, Dept Clin Mol Biol, Oslo, Norway.
[Zheng, Wei; Shrubsole, Martha; Shu, Xiao-Ou; Blot, William; Cai, Qiuyin] Vanderbilt Univ, Sch Med, Vanderbilt Ingram Canc Ctr, Div Epidemiol,Dept Med, Nashville, TN 37212 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] Northern Finland Lab Ctr NordLab, Lab Canc Genet & Tumor Biol, Oulu, Finland.
[Jukkola-Vuorinen, Arja] Univ Oulu, Dept Oncol, Oulu Univ Hosp, Oulu, 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.
[Knight, Julia A.] Mt Sinai Hosp, Prosserman Ctr Hlth Res, Lunenfeld Tanenbaum Res Inst, Toronto, ON, Canada.
[Knight, Julia A.] Univ Toronto, Div Epidemiol, Dalla Lana Sch Publ Hlth, Toronto, ON, Canada.
[Devilee, Peter] Leiden Univ, Med Ctr, Dept Pathol, Leiden, Netherlands.
[Devilee, Peter] Leiden Univ, Med Ctr, Dept Human Genet, Leiden, Netherlands.
[Seynaeve, Caroline; Hollestelle, Antoinette; Martens, John W. M.] Erasmus MC Canc Inst, Dept Med Oncol, Family Canc Clin, Rotterdam, Netherlands.
[Garcia-Closas, Montserrat; Swerdlow, Anthony] Inst Canc Res, Div Genet & Epidemiol, London, England.
[Czene, Kamila; Darabi, Hatef; Li, Jingmei; Hall, Per] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
[Lu, Wei] Shanghai Ctr Dis Control & Prevent, Shanghai, Peoples R China.
[Cox, Angela] Univ Sheffield, Sheffield Canc Res, Dept Oncol, Sheffield, S Yorkshire, England.
[Cross, Simon S.] Univ Sheffield, Acad Unit Pathol, Dept Neurosci, Sheffield, S Yorkshire, England.
[Blot, William] Int Epidemiol Inst, Rockville, MD USA.
[Shah, Mitul; Luccarini, Craig; Baynes, Caroline; Harrington, Patricia; Pharoah, Paul D. P.; Easton, Douglas F.; Dunning, Alison M.] Univ Cambridge, Ctr Canc Genet Epidemiol, Dept Oncol, Cambridge, England.
[Kang, Daehee] Seoul Natl Univ, Coll Med, Dept Prevent Med, Seoul, South Korea.
[Kang, Daehee; Choi, Ji-Yeob] Seoul Natl Univ, Coll Med, Dept Biomed Sci, Seoul, South Korea.
[Kang, Daehee; Choi, Ji-Yeob] Seoul Natl Univ, Canc Res Inst, Seoul, South Korea.
[Hartman, Mikael; Chia, Kee Seng] Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore.
[Hartman, Mikael] Natl Univ Hlth Syst, Dept Surg, Singapore, Singapore.
[Torres, Diana] Pontificia Univ Javeriana, Inst Human Genet, Bogota, Colombia.
[Jakubowska, Anna; Lubinski, Jan] Pomeranian Med Univ, Dept Genet & Pathol, Szczecin, Poland.
[Sangrajrang, Suleeporn] Natl Canc Inst, Bangkok, Thailand.
[Brennan, Paul] Int Agcy Res Canc, Lyon, France.
[Yannoukakos, Drakoulis] Natl Ctr Sci Res Demokritos, Mol Diagnost Lab, IRRP, Athens, Greece.
[Shen, Chen-Yang] China Med Univ, Sch Publ Hlth, Taichung, Taiwan.
[Shen, Chen-Yang] Acad Sinica, Taiwan Biobank, Inst Biomed Sci, Taipei, Taiwan.
[Hou, Ming-Feng] Kaohsiung Med Univ, Ctr Canc, Chung Ho Mem Hosp, Kaohsiung, Taiwan.
[Hou, Ming-Feng] Kaohsiung Med Univ, Dept Surg, Chung Ho Mem Hosp, Kaohsiung, Taiwan.
[Simard, Jacques] Univ Laval, Ctr Hosp Univ Quebec, Res Ctr, Quebec City, PQ, Canada.
[Figueroa, Jonine D.] Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Edinburgh, Midlothian, Scotland.
[Figueroa, Jonine D.] Univ Edinburgh, Edinburgh Canc Res UK Ctr, Edinburgh, Midlothian, Scotland.
RP Figueroa, JD (reprint author), NCI, Div Canc Epidemiol & Genet, Rockville, MD USA.; Figueroa, JD (reprint author), Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Edinburgh, Midlothian, Scotland.; Figueroa, JD (reprint author), Univ Edinburgh, Edinburgh Canc Res UK Ctr, Edinburgh, Midlothian, Scotland.
EM jonine.figueroa@ed.ac.uk
RI Knight, Julia/A-6843-2012; Zheng, Wei/O-3351-2013; Dork,
Thilo/J-8620-2012; Zhang, Han/K-2118-2016; Li, Jingmei/I-2904-2012;
Brenner, Hermann/B-4627-2017;
OI Zheng, Wei/0000-0003-1226-070X; Zhang, Han/0000-0001-7977-9616; Li,
Jingmei/0000-0001-8587-7511; Brenner, Hermann/0000-0002-6129-1572; Khan,
Sofia/0000-0003-4185-8882; Matsuo, Keitaro/0000-0003-1761-6314;
Yannoukakos, Drakoulis/0000-0001-7509-3510; Dunning, Alison
Margaret/0000-0001-6651-7166
FU Cancer Research UK [10124]; NCI NIH HHS [R01 CA176785]
NR 43
TC 1
Z9 1
U1 6
U2 6
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 AUG 24
PY 2016
VL 11
IS 8
AR e0160316
DI 10.1371/journal.pone.0160316
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DU5NI
UT WOS:000382258100011
PM 27556229
ER
PT J
AU Tunstall, BJ
Carmack, SA
AF Tunstall, Brendan J.
Carmack, Stephanie A.
TI Social Stress-Induced Alterations in CRF Signaling in the VTA Facilitate
the Emergence of Addiction-like Behavior
SO JOURNAL OF NEUROSCIENCE
LA English
DT Editorial Material
ID CORTICOTROPIN-RELEASING-FACTOR; VENTRAL TEGMENTAL AREA; COCAINE SEEKING;
BINDING-PROTEIN; INDUCED RELAPSE; FACTOR NEURONS; DOPAMINE; RATS;
VASOPRESSIN; RECEPTORS
C1 [Tunstall, Brendan J.; Carmack, Stephanie A.] NIDA, NIH, Baltimore, MD 21224 USA.
RP Tunstall, BJ (reprint author), NIDA, Intramural Res Program, 251 Bayview Blvd,BRC 08A406-17, Baltimore, MD 21224 USA.
EM brendan.tunstall@nih.gov
NR 29
TC 0
Z9 0
U1 3
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 AUG 24
PY 2016
VL 36
IS 34
BP 8780
EP 8782
DI 10.1523/JNEUROSCI.1815-16.2016
PG 3
WC Neurosciences
SC Neurosciences & Neurology
GA DW9SW
UT WOS:000384004000002
PM 27559161
ER
PT J
AU Henriksen, S
Read, JCA
Cumming, BG
AF Henriksen, Sid
Read, Jenny C. A.
Cumming, Bruce G.
TI Neurons in Striate Cortex Signal Disparity in Half-Matched Random-Dot
Stereograms
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
DE binocular; correspondence problem; disparity; half-matched; random dot
stereogram; stereopsis
ID STEREOSCOPIC DEPTH-PERCEPTION; SINGLE-NEURON; V1 NEURONS;
HORIZONTAL-DISPARITY; BINOCULAR DISPARITY; VISUAL-CORTEX; AWAKE MONKEYS;
ENERGY-MODEL; RESPONSES; MACAQUE
AB Human stereopsis can operate in dense "cyclopean" images containing no monocular objects. This is believed to depend on the computation of binocular correlation by neurons in primary visual cortex (V1). The observation that humans perceive depth in half-matched random-dot stereograms, although these stimuli have no net correlation, has led to the proposition that human depth perception in these stimuli depends on a distinct "matching" computation possibly performed in extrastriate cortex. However, recording from disparity-selective neurons in V1 of fixating monkeys, we found that they are in fact able to signal disparity in half-matched stimuli. We present a simple model that explains these results. This reinstates the view that disparity-selective neurons in V1 provide the initial substrate for perception in dense cyclopean stimuli, and strongly suggests that separate correlation and matching computations are not necessary to explain existing data on mixed correlation stereograms.
C1 [Henriksen, Sid; Read, Jenny C. A.] Newcastle Univ, Inst Neurosci, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England.
[Henriksen, Sid; Cumming, Bruce G.] NEI, Lab Sensorimotor Res, NIH, Bethesda, MD 20892 USA.
RP Henriksen, S (reprint author), NIH, 49 Convent Dr, Bethesda, MD 20892 USA.
EM sid.henriksen@gmail.com
OI Read, Jenny/0000-0002-9029-5185
FU Wellcome Trust/National Institutes of Health joint PhD Studentship
[100931/Z/13/Z]; Intramural Research Program at the National Eye
Institute/National Institutes of Health
FX This work was supported by a Wellcome Trust/National Institutes of
Health joint PhD Studentship (100931/Z/13/Z) to S.H., and by the
Intramural Research Program at the National Eye Institute/National
Institutes of Health to B.G.C.
NR 37
TC 0
Z9 0
U1 1
U2 1
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 AUG 24
PY 2016
VL 36
IS 34
BP 8967
EP 8976
DI 10.1523/JNEUROSCI.0642-16.2016
PG 10
WC Neurosciences
SC Neurosciences & Neurology
GA DW9SW
UT WOS:000384004000018
PM 27559177
ER
PT J
AU Serra-Musach, J
Mateo, F
Capdevila-Busquets, E
de Garibay, GR
Zhang, XH
Guha, R
Thomas, CJ
Grueso, J
Villanueva, A
Jaeger, S
Heyn, H
Vizoso, M
Perez, H
Cordero, A
Gonzalez-Suarez, E
Esteller, M
Moreno-Bueno, G
Tjarnberg, A
Lazaro, C
Serra, V
Arribas, J
Benson, M
Gustafsson, M
Ferrer, M
Aloy, P
Pujana, MA
AF Serra-Musach, Jordi
Mateo, Francesca
Capdevila-Busquets, Eva
de Garibay, Gorka Ruiz
Zhang, Xiaohu
Guha, Raj
Thomas, Craig J.
Grueso, Judit
Villanueva, Alberto
Jaeger, Samira
Heyn, Holger
Vizoso, Miguel
Perez, Hector
Cordero, Alex
Gonzalez-Suarez, Eva
Esteller, Manel
Moreno-Bueno, Gema
Tjaernberg, Andreas
Lazaro, Conxi
Serra, Violeta
Arribas, Joaquin
Benson, Mikael
Gustafsson, Mika
Ferrer, Marc
Aloy, Patrick
Pujana, Miquel Angel
TI Cancer network activity associated with therapeutic response and
synergism
SO GENOME MEDICINE
LA English
DT Article
DE Cancer; Network; Therapy; Synergy
ID PROTEIN-INTERACTION NETWORKS; BREAST-CANCER; DRUG-RESISTANCE; SIGNALING
ENTROPY; SYSTEMS BIOLOGY; CELLS; COMBINATION; SENSITIVITY; ROBUSTNESS;
EXPRESSION
AB Background: Cancer patients often show no or only modest benefit from a given therapy. This major problem in oncology is generally attributed to the lack of specific predictive biomarkers, yet a global measure of cancer cell activity may support a comprehensive mechanistic understanding of therapy efficacy. We reasoned that network analysis of omic data could help to achieve this goal.
Methods: A measure of "cancer network activity" (CNA) was implemented based on a previously defined network feature of communicability. The network nodes and edges corresponded to human proteins and experimentally identified interactions, respectively. The edges were weighted proportionally to the expression of the genes encoding for the corresponding proteins and relative to the number of direct interactors. The gene expression data corresponded to the basal conditions of 595 human cancer cell lines. Therapeutic responses corresponded to the impairment of cell viability measured by the half maximal inhibitory concentration (IC50) of 130 drugs approved or under clinical development. Gene ontology, signaling pathway, and transcription factor-binding annotations were taken from public repositories. Predicted synergies were assessed by determining the viability of four breast cancer cell lines and by applying two different analytical methods.
Results: The effects of drug classes were associated with CNAs formed by different cell lines. CNAs also differentiate target families and effector pathways. Proteins that occupy a central position in the network largely contribute to CNA. Known key cancer-associated biological processes, signaling pathways, and master regulators also contribute to CNA. Moreover, the major cancer drivers frequently mediate CNA and therapeutic differences. Cell-based assays centered on these differences and using uncorrelated drug effects reveals novel synergistic combinations for the treatment of breast cancer dependent on PI3K-mTOR signaling.
Conclusions: Cancer therapeutic responses can be predicted on the basis of a systems-level analysis of molecular interactions and gene expression. Fundamental cancer processes, pathways, and drivers contribute to this feature, which can also be exploited to predict precise synergistic drug combinations.
C1 [Zhang, Xiaohu; Guha, Raj; Thomas, Craig J.; Ferrer, Marc] NIH, NCATS, Div Preclin Innovat, 9800 Med Ctr Dr Rockville, Bethesda, MD 20850 USA.
[Capdevila-Busquets, Eva; Jaeger, Samira; Aloy, Patrick] Barcelona Inst Sci & Technol, IRB Barcelona, Joint IRB BSC CRG Program Computat Biol, Baldiri Reixac 10, Barcelona 08028, Catalonia, Spain.
[Serra-Musach, Jordi; Mateo, Francesca; de Garibay, Gorka Ruiz; Villanueva, Alberto; Pujana, Miquel Angel] Bellvitge Inst Biomed Res IDIBELL, Catalan Inst Oncol ICO, Program Canc Therapeut Resistance ProCURE, Breast Canc & Syst Biol Lab, Gran Via 199,Lhosp Llobregat, Barcelona 08908, Catalonia, Spain.
[Grueso, Judit; Serra, Violeta] VHIO, Cellex Ctr, Expt Therapeut Grp, Natzaret 115-117, Barcelona 08035, Catalonia, Spain.
[Heyn, Holger; Vizoso, Miguel; Perez, Hector; Cordero, Alex; Gonzalez-Suarez, Eva; Esteller, Manel] IDIBELL, Cancer Epigenet & Biol Program PEBC, Gran Via 199, Barcelona 08908, Catalonia, Spain.
[Esteller, Manel] Univ Barcelona, Sch Med, Dept Physiol Sci 2, Feixa Llarga S-N, Barcelona 08908, Catalonia, Spain.
[Esteller, Manel] Univ Barcelona, Sch Med, Dept Physiol Sci 2, Feixa Llarga S-N, Barcelona 08010, Catalonia, Spain.
[Esteller, Manel; Arribas, Joaquin; Aloy, Patrick] ICREA, Passeig Lluis Companys 23, Barcelona 08010, Catalonia, Spain.
[Moreno-Bueno, Gema] Autonomous Univ Madrid, Biomed Res Inst Alberto Sols, Spanish Natl Res Council CSIC, Hosp La Paz Inst Hlth Res IdiPAZ,Dept Biochem, Arzobispo Morcillo 4, E-28029 Madrid, Spain.
[Moreno-Bueno, Gema] MD Anderson Int Fdn, Arturo Soria 270, Madrid 28033, Spain.
[Tjaernberg, Andreas; Benson, Mikael; Gustafsson, Mika] Linkoping Univ, Ctr Individualized Med, Dept Clin & Expt Med, S-58183 Linkoping, Sweden.
[Lazaro, Conxi] IDIBELL, ICO, Hereditary Canc Program, Gran Via 199, Barcelona 08908, Catalonia, Spain.
[Arribas, Joaquin] VHIO, Cellex Ctr, Preclin Res Program, Natzaret 115-117, Barcelona 08035, Catalonia, Spain.
[Arribas, Joaquin] Autonomous Univ Barcelona, Med Sch Bldg M, Dept Biochem & Mol Biol, Bellaterra 08193, Catalonia, Spain.
RP Ferrer, M (reprint author), NIH, NCATS, Div Preclin Innovat, 9800 Med Ctr Dr Rockville, Bethesda, MD 20850 USA.; Aloy, P (reprint author), Barcelona Inst Sci & Technol, IRB Barcelona, Joint IRB BSC CRG Program Computat Biol, Baldiri Reixac 10, Barcelona 08028, Catalonia, Spain.; Pujana, MA (reprint author), Bellvitge Inst Biomed Res IDIBELL, Catalan Inst Oncol ICO, Program Canc Therapeut Resistance ProCURE, Breast Canc & Syst Biol Lab, Gran Via 199,Lhosp Llobregat, Barcelona 08908, Catalonia, Spain.; Aloy, P (reprint author), ICREA, Passeig Lluis Companys 23, Barcelona 08010, Catalonia, Spain.
EM marc.ferrer@nih.gov; paloy@irbbarcelona.org; mapujana@iconcologia.net
RI Moreno-Bueno, Gema/K-9354-2016; Mateo, Francesca/K-7746-2015;
OI Moreno-Bueno, Gema/0000-0002-5030-6687; Mateo,
Francesca/0000-0002-2342-7010; Heyn, Holger/0000-0002-3276-1889
FU Generalitat de Catalunya AGAUR SGR [364]; Spanish Ministry of Health
ISCIII [PI12/01528, PI15/00854, RTICC RD12/0036/0007, 0008]; Spanish
Ministry of Science and Innovation "Fondo Europeo de Desarrollo Regional
(FEDER), una manera de hacer Europa" [PIE13/00022-ONCOPROFILE];
Telemaraton "Todos Somos Raros, Todos Somos Unicos" [P35]
FX This study was supported by Generalitat de Catalunya AGAUR SGR 2014
grant 364, Spanish Ministry of Health ISCIII grants PI12/01528,
PI15/00854, RTICC RD12/0036/0007 and 0008, and PIE13/00022-ONCOPROFILE,
Spanish Ministry of Science and Innovation "Fondo Europeo de Desarrollo
Regional (FEDER), una manera de hacer Europa", and the Telemaraton 2014
"Todos Somos Raros, Todos Somos Unicos" grant P35.
NR 59
TC 1
Z9 1
U1 7
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 AUG 24
PY 2016
VL 8
AR 88
DI 10.1186/s13073-016-0340-x
PG 12
WC Genetics & Heredity
SC Genetics & Heredity
GA DU8HR
UT WOS:000382454400002
PM 27553366
ER
PT J
AU Francis, WR
Christianson, LM
Powers, ML
Schnitzler, CE
Haddock, SHD
AF Francis, Warren R.
Christianson, Lynne M.
Powers, Meghan L.
Schnitzler, Christine E.
Haddock, Steven H. D.
TI Non-excitable fluorescent protein orthologs found in ctenophores
SO BMC EVOLUTIONARY BIOLOGY
LA English
DT Article
DE Fluorescent protein; Ctenophore; Siphonophore; Transcriptome;
Fluorescence; Haeckelia
ID GFP-LIKE PROTEINS; GENOMIC ORGANIZATION; EVOLUTION; AEQUOREA; CORAL;
SEA; BIOLUMINESCENCE; EXPRESSION; VERSION; FAMILY
AB Background: Fluorescent proteins are optically active proteins found across many clades in metazoans. A fluorescent protein was recently identified in a ctenophore, but this has been suggested to derive from a cnidarian, raising again the question of origins of this group of proteins.
Results: Through analysis of transcriptome data from 30 ctenophores, we identified a member of an orthologous group of proteins similar to fluorescent proteins in each of them, as well as in the genome of Mnemiopsis leidyi. These orthologs lack canonical residues involved in chromophore formation, suggesting another function.
Conclusions: The phylogenetic position of the ctenophore protein family among fluorescent proteins suggests that this gene was present in the common ancestor of all ctenophores and that the fluorescent protein previously found in a ctenophore actually derives from a siphonophore.
C1 [Francis, Warren R.; Christianson, Lynne M.; Powers, Meghan L.; Haddock, Steven H. D.] Monterey Bay Aquarium Res Inst, 7700 Sandholdt Rd, Moss Landing, CA 95039 USA.
[Schnitzler, Christine E.] NHGRI, NIH, 50 South Dr, Bethesda, MD 20892 USA.
[Francis, Warren R.] Univ Munich, Munich, Germany.
[Schnitzler, Christine E.] Univ Florida, Whitney Lab Marine Biosci, St Augustine, FL 32080 USA.
RP Haddock, SHD (reprint author), Monterey Bay Aquarium Res Inst, 7700 Sandholdt Rd, Moss Landing, CA 95039 USA.
EM haddock@mbari.org
FU David and Lucile Packard Foundation; National Institute of General
Medical Sciences at the National Institutes of Health
[NIGMS:5-R01-GM087198]; Intramural Research Program of the National
Human Genome Research Institute, National Institutes of Health
FX This work was supported by the David and Lucile Packard Foundation and
funded by the National Institute of General Medical Sciences at the
National Institutes of Health (NIGMS:5-R01-GM087198) to SHDH. This work
was also supported in part by the Intramural Research Program of the
National Human Genome Research Institute, National Institutes of Health
to CES.
NR 49
TC 0
Z9 0
U1 14
U2 14
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2148
J9 BMC EVOL BIOL
JI BMC Evol. Biol.
PD AUG 24
PY 2016
VL 16
AR 167
DI 10.1186/s12862-016-0738-5
PG 8
WC Evolutionary Biology; Genetics & Heredity
SC Evolutionary Biology; Genetics & Heredity
GA DT9JG
UT WOS:000381814600002
PM 27557948
ER
PT J
AU Liu, JF
Huang, SG
Su, XZ
Song, JP
Lu, FL
AF Liu, Jinfeng
Huang, Shiguang
Su, Xin-zhuan
Song, Jianping
Lu, Fangli
TI Blockage of Galectin-receptor Interactions by alpha-lactose Exacerbates
Plasmodium berghei-induced Pulmonary Immunopathology
SO SCIENTIFIC REPORTS
LA English
DT Article
ID PROTEIN DISULFIDE-ISOMERASE; ENTERICA SEROVAR TYPHIMURIUM; REGULATORY
T-CELLS; ACUTE LUNG INJURY; MALARIA INFECTIONS; CEREBRAL MALARIA;
MACROPHAGES; INFLAMMATION; TIM-3; INTERFERONS
AB Malaria-associated acute lung injury (ALI) is a frequent complication of severe malaria that is often caused by "excessive" immune responses. To better understand the mechanism of ALI in malaria infection, here we investigated the roles of galectin (Gal)-1, 3, 8, 9 and the receptors of Gal-9 (Tim-3, CD44, CD137, and PDI) in malaria-induced ALI. We injected alpha (alpha)-lactose into mice-infected with Plasmodium berghei ANKA (PbANKA) to block galectins and found significantly elevated total proteins in bronchoalveolar lavage fluid, higher parasitemia and tissue parasite burden, and increased numbers of CD68(+) alveolar macrophages as well as apoptotic cells in the lungs after blockage. Additionally, mRNA levels of Gal-9, Tim-3, CD44, CD137, and PDI were significantly increased in the lungs at day 5 after infection, and the levels of CD137, IFN-alpha, IFN-beta, IFN-gamma, IL-4, and IL-10 in the lungs were also increased after alpha-lactose treatment. Similarly, the levels of Gal-9, Tim-3, IFN-alpha, IFN-beta, IFN-gamma, and IL-10 were all significantly increased in murine peritoneal macrophages co-cultured with PbANKA-infected red blood cells in vitro; but only IFN-alpha and IFN-beta were significantly increased after alpha-lactose treatment. Our data indicate that Gal-9 interaction with its multiple receptors play an important role in murine malaria-associated ALI.
C1 [Liu, Jinfeng; Lu, Fangli] Sun Yat Sen Univ, Zhongshan Sch Med, Dept Parasitol, Guangzhou 510080, Guangdong, Peoples R China.
[Liu, Jinfeng; Lu, Fangli] Sun Yat Sen Univ, Minist Educ, Key Lab Trop Dis Control, Guangzhou 510080, Guangdong, Peoples R China.
[Huang, Shiguang] Jinan Univ, Sch Med, Guangzhou 510632, Guangdong, Peoples R China.
[Su, Xin-zhuan] NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA.
[Su, Xin-zhuan] Xiamen Univ, Sch Life Sci, Innovat Ctr Cell Signaling Network, State Key Lab Cellular Stress Biol, Xiamen 361005, Fujian, Peoples R China.
[Song, Jianping] Guangzhou Univ Chinese Med, Inst Sci & Technol, 436 Chentai Rd, Guangzhou 510445, Guangdong, Peoples R China.
RP Lu, FL (reprint author), Sun Yat Sen Univ, Zhongshan Sch Med, Dept Parasitol, Guangzhou 510080, Guangdong, Peoples R China.; Lu, FL (reprint author), Sun Yat Sen Univ, Minist Educ, Key Lab Trop Dis Control, Guangzhou 510080, Guangdong, Peoples R China.; Su, XZ (reprint author), NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA.; Su, XZ (reprint author), Xiamen Univ, Sch Life Sci, Innovat Ctr Cell Signaling Network, State Key Lab Cellular Stress Biol, Xiamen 361005, Fujian, Peoples R China.
EM xsu@niaid.nih.gov; fanglilu@yahoo.com
FU Natural Science Foundation of China [81271854, 81471973, 81273643];
Science and Technology Planning Project of Guangdong Province, China
[2014A020212108, 2013B021800043, 2014A020212212, 2014B050502013];
Project 111 of the State Bureau of Foreign Experts and Ministry of
Education of China [B06016]; Division of Intramural Research at the
National Institute of Allergy and Infectious Diseases, National
Institutes of Health; Natural Science Foundation of Guangdong Province,
China [S2013010016736]
FX Research reported in this publication was supported in part by the
Natural Science Foundation of China (Nos 81271854 and 81471973), the
Science and Technology Planning Project of Guangdong Province, China
(No. 2014A020212108), and the Project 111 of the State Bureau of Foreign
Experts and Ministry of Education of China (B06016) (F. Lu); by the
Division of Intramural Research at the National Institute of Allergy and
Infectious Diseases, National Institutes of Health (X.-z. Su); by the
Science and Technology Planning Project of Guangdong Province, China
(Nos 2013B021800043 and 2014A020212212) (S. Huang); by the Natural
Science Foundation of China (No. 81273643); the Natural Science
Foundation of Guangdong Province, China (No. S2013010016736), and the
Science and Technology Planning Project of Guangdong Province, China
(No. 2014B050502013) (J. Song). The authors thank Cindy Clark, NIH
Library Writing Center, for manuscript editing assistance.
NR 59
TC 0
Z9 0
U1 5
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 AUG 24
PY 2016
VL 6
AR 32024
DI 10.1038/srep32024
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DT9WM
UT WOS:000381853000002
PM 27554340
ER
PT J
AU Hsu, DC
Ma, YF
Hur, S
Li, D
Rupert, A
Scherzer, R
Kalapus, SC
Deeks, S
Sereti, I
Hsue, PY
AF Hsu, Denise C.
Ma, Yi Fei
Hur, Sophia
Li, Danny
Rupert, Adam
Scherzer, Rebecca
Kalapus, S. C.
Deeks, Steven
Sereti, Irini
Hsue, Priscilla Y.
TI Plasma IL-6 levels are independently associated with atherosclerosis and
mortality in HIV-infected individuals on suppressive antiretroviral
therapy
SO AIDS
LA English
DT Article
DE atherosclerosis; CCR5; HIV; IL-6; immune activation
ID INTIMA-MEDIA THICKNESS; CORONARY-HEART-DISEASE; T-CELL-ACTIVATION;
SUBCLINICAL VASCULAR-DISEASE; CARDIOVASCULAR RISK-FACTORS; CAROTID
ATHEROSCLEROSIS; MYOCARDIAL-INFARCTION; RHEUMATOID-ARTHRITIS;
INFLAMMATORY MARKERS; MONOCYTE-ACTIVATION
AB Objective: To determine the associations of markers of immune activation with atherosclerosis and mortality, in participants with treated and suppressed HIV infection.
Design: Observational study of 149 HIV-infected participants with virologic suppression on antiretroviral therapy.
Methods: Cryopreserved mononuclear cells and plasma were used to evaluate markers of T cell and monocyte activation, inflammation and coagulopathy. Carotid artery intima-media thickness (CIMT) was measured by high-resolution ultrasound at the common, bifurcation and internal carotid regions. Associations of immunologic markers with CIMT and all-cause mortality were assessed using multivariable linear regression and Cox proportional hazards regression.
Results: The majority of participants were men (93%) and white (67%), median age of 48.5 years and median CD4(+) T-cell count of 522 cells/mu l. The median baseline IMT was 1.0 mm. Over a median of 8.3-year follow-up, 12 deaths occurred. In multivariate analysis, adjusted for traditional cardiovascular risk factors, higher monocyte C-C motif chemokine receptor 5 (CCR5) expression [5.4%, P = 0.001] was associated with greater common CIMT. Higher plasma IL-6 was associated with greater bifurcation [8.0%, P = 0.007] and overall mean IMT [5.2%, P = 0.026]. Finally, higher plasma IL-6 [hazard ratio 1.9, P = 0.030], internal carotid [hazard ratio 4.1, P = 0.022] and mean IMT [hazard ratio 5.2, P = 0.026] were individually associated with all-cause mortality.
Conclusion: Higher monocyte CCR5 expression and plasma IL-6 were associated with atherosclerosis, independent of traditional cardiovascular risk factors. IL-6 and CIMT were individually associated with all-cause mortality. The impact of therapies targeting immune activation in cardiovascular disease in treated HIV infection merits additional investigation. Copyright (C) 2016 Wolters Kluwer Health, Inc. All rights reserved.
C1 [Hsu, Denise C.; Sereti, Irini] NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Ma, Yi Fei; Hur, Sophia; Li, Danny; Kalapus, S. C.; Deeks, Steven; Hsue, Priscilla Y.] Univ Calif San Francisco, Room 5G1 Cardiol SFGH,1001 Potrero Ave, San Francisco, CA 94110 USA.
[Rupert, Adam] Leidos Biomed Res Inc, Frederick, MD USA.
[Scherzer, Rebecca] Vet Affairs Med Ctr, San Francisco, CA 94121 USA.
RP Hsue, PY (reprint author), Univ Calif San Francisco, Room 5G1 Cardiol SFGH,1001 Potrero Ave, San Francisco, CA 94110 USA.
EM Priscilla.Hsue@ucsf.edu
FU National Cancer Institute, National Institutes of Health
[HHSN261200800001E]; National Institute of Allergy and Infectious
Diseases [K24AI112393]; NIAID/NIH; NIAID [K24AI069994]; UCSF/Gladstone
Institute of Virology & Immunology CFAR [P30 AI027763]; UCSF Clinical
and Translational Research Institute Clinical Research Center [UL1
RR024131]; CFAR Network of Integrated Systems [R24 AI067039]
FX The project has been funded in part with Federal funds from the National
Cancer Institute, National Institutes of Health, under contract no.
HHSN261200800001E (A.R.) and by the National Institute of Allergy and
Infectious Diseases K24AI112393 (P.Y.H.). This project has also been
funded in part by the intramural program of NIAID/NIH. The SCOPE cohort
was supported in part by the NIAID (K24AI069994), the UCSF/Gladstone
Institute of Virology & Immunology CFAR (P30 AI027763), the UCSF
Clinical and Translational Research Institute Clinical Research Center
(UL1 RR024131) and the CFAR Network of Integrated Systems (R24
AI067039). 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.
NR 76
TC 2
Z9 2
U1 1
U2 5
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 AUG 24
PY 2016
VL 30
IS 13
BP 2065
EP 2074
DI 10.1097/QAD.0000000000001149
PG 10
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA DS5HN
UT WOS:000380812400007
PM 27177313
ER
PT J
AU Chan, ES
Landay, AL
Brown, TT
Ribaudo, HJ
Mirmonsef, P
Ofotokun, I
Weitzmann, MN
Martinson, J
Klingman, KL
Eron, JJ
Fichtenbaum, CJ
Plants, J
Taiwo, BO
AF Chan, Ellen S.
Landay, Alan L.
Brown, Todd T.
Ribaudo, Heather J.
Mirmonsef, Paria
Ofotokun, Igho
Weitzmann, M. Neale
Martinson, Jeffrey
Klingman, Karin L.
Eron, Joseph J.
Fichtenbaum, Carl J.
Plants, Jill
Taiwo, Babafemi O.
TI Differential CD4(+) cell count increase and CD4(+): CD8(+) ratio
normalization with maraviroc compared with tenofovir
SO AIDS
LA English
DT Article
DE CD4 lymphocyte count; CD4: CD8 ratio; HIV; inflammation; maraviroc;
tenofovir
ID ANTIRETROVIRAL THERAPY; IMMUNE ACTIVATION; CLINICAL-TRIALS; HIV;
INFLAMMATION; SUPPRESSION; INDIVIDUALS; RECOVERY; MARKERS; EVENTS
AB Objective: Studies exploring the immunologic effects of maraviroc (MVC) have produced mixed results; hence, it remains unclear whether MVC has unique immunologic effects in comparison with other antiretroviral drugs. We sought to determine whether MVC has differential effects compared with tenofovir disoproxil fumarate (TDF) during initial antiretroviral therapy.
Design: Prospective study in AIDS Clinical Trials Group A5303, a double-blind, placebo-controlled trial (N = 262) of MVC vs. TDF, each combined with boosted darunavir and emtricitabine.
Methods: A total of 31 cellular and soluble biomarkers were assayed at weeks 0 and 48. Polychromatic flow cytometry was performed on cryopreserved peripheral blood mononuclear cells. Soluble markers were assayed in plasma using ELISA kits. Analyses were as treated.
Results: Analyses included 230 participants (119 in MVC arm and 111 in TDF arm). Over 48 weeks of treatment, no significant differences were detected in declines in markers of inflammation and activation with MVC vs. TDF. A greater CD4(+) T-cell count increase (median +234 vs. +188 cells/mu l, P = 0.036), a smaller CD8(+) T-cell count decrease (-6 vs. -109 cells/mu l, P = 0.008), and a smaller CD4(+) : CD8(+) ratio increase (0.26 vs. 0.39, P = 0.003) occurred with MVC. Among participants with a baseline CD4(+) : CD8(+) ratio less than 1, a smaller proportion of MVC group normalized to a ratio greater than 1 at week 48 (15 and 36%, P < 0.001).
Conclusion: MVC resulted in less improvement in the CD4(+) : CD8(+) ratio driven by greater increase in CD4(+) cell count but smaller decline in CD8(+) cell count. Changes in soluble or cellular biomarkers of inflammation and immune activation were not different between MVC and TDF. Copyright (C) 2016 Wolters Kluwer Health, Inc. All rights reserved.
C1 [Chan, Ellen S.; Ribaudo, Heather J.] Harvard Chan Sch Publ Hlth, Stat & Data Anal Ctr, 651 Huntington Ave,FXB 539, Boston, MA 02115 USA.
[Landay, Alan L.; Mirmonsef, Paria; Martinson, Jeffrey; Plants, Jill] Rush Univ, Med Ctr, Dept Immunol & Microbiol, Chicago, IL 60612 USA.
[Brown, Todd T.] Johns Hopkins Univ, Div Endocrinol Diabet & Metab, Baltimore, MD USA.
[Ofotokun, Igho] Emory Univ, Div Infect Dis, Atlanta, GA 30322 USA.
[Weitzmann, M. Neale] Emory Univ, Div Endocrinol & Metab & Lipids, Atlanta, GA 30322 USA.
[Weitzmann, M. Neale] Atlanta VA Med Ctr, Decatur, GA USA.
[Klingman, Karin L.] NIAID, HIV Res Branch, Div Aids, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Eron, Joseph J.] Univ N Carolina, Div Infect Dis, Chapel Hill, NC USA.
[Fichtenbaum, Carl J.] Univ Cincinnati, Div Infect Dis, Cincinnati, OH USA.
[Taiwo, Babafemi O.] Northwestern Univ, Div Infect Dis, Chicago, IL 60611 USA.
RP Chan, ES (reprint author), Harvard Chan Sch Publ Hlth, Stat & Data Anal Ctr, 651 Huntington Ave,FXB 539, Boston, MA 02115 USA.
EM echan@sdac.harvard.edu; echan@sdac.harvard.edu; echan@sdac.harvard.edu
FU National Institute of Allergy and Infectious Diseases [U01AI068636];
National Institute of Mental Health (NIMH), National Institute of Dental
and Craniofacial Research (NIDCR); NIH [AI068634, AI068636, AI69439, UM1
AI069496, 5UM1AI069412, UM1 AI069423, 1UL1TR001111, P30 AI50410,
2UMIA1069423-08, 2UM1AI069418-08, 2P30 AI 50409-10, UL1TR000454]; NIH
(National Center for Advancing Translational Sciences/NIH) [UMAI069494,
UMAI069432, UM1AI 069471, UM1AI069452, UM1 AI069501, 2UM1AI069432, UL1
TR001082, 1U01AI069477-01, P30AI073961, 5UM1 AI068636, 2UM1AI069503, UM1
AI069471, 2UM1AI06943908, UL1 TR000445]; National Institute of Health
[AI069501, 5UM1AI069415-10, 2UM1AI069412-08, AI069424, UL1 RR025780,
2UM1-AI069470-08, UM1AI069472, 2UMAI069432, AI 69501, UM1AI069471, UM1A
068636-09, 5 P30 AI-045008-15, U01AI069447, NO1-HD-3-3345, UMI AI069511,
UM1 AI069465, UL1TR001079, UL1 RR024160, UL1 TR000042]
FX This work was supported by (Award Number U01AI068636) 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. This work was also supported by grants
from the NIH [(grant numbers AI068634 and AI068636) to the ACTG
Statistical Data Analysis Center (to E.S.C. and H.J.R.), (grant number
AI068636) to the Rush University Medical Center (to A.L.L., P.M,J.M, and
J.P.), and to the research sites that participated in the study (grant
numbers UMAI069494, UMAI069432, UM1AI 069471, UM1AI069452, UM1 AI069501,
2UM1AI069432, UL1 TR001082, 1U01AI069477-01, P30AI073961, 5UM1 AI068636,
2UM1AI069503, UM1 AI069471, 2UM1AI06943908, and UL1 TR000445 from the
National Center for Advancing Translational Sciences/NIH, AI69439, UM1
AI069496, 5UM1AI069412, UM1 AI069423, 1UL1TR001111, P30 AI50410,
2UMIA1069423-08, 2UM1AI069418-08, 2P30 AI 50409-10, UL1TR000454,
AI069501, 5UM1AI069415-10, 2UM1AI069412-08, AI069424, UL1 RR025780,
2UM1-AI069470-08, UM1AI069472, 2UMAI069432, AI 69501, UM1AI069471, UM1A
068636-09, 5 P30 AI-045008-15, U01AI069447, NO1-HD-3-3345, UMI AI069511,
UM1 AI069465, UL1TR001079, UL1 RR024160, and UL1 TR000042)]. ViiV,
Gilead, and AbbVie provided study drugs. The funders had no role in
study design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 14
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 0269-9370
EI 1473-5571
J9 AIDS
JI Aids
PD AUG 24
PY 2016
VL 30
IS 13
BP 2091
EP 2097
DI 10.1097/QAD.0000000000001181
PG 7
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA DS5HN
UT WOS:000380812400010
PM 27281061
ER
PT J
AU Khatami, M
AF Khatami, Mahin
TI Is cancer a severe delayed hypersensitivity reaction and histamine a
blueprint?
SO CLINICAL AND TRANSLATIONAL MEDICINE
LA English
DT Article
DE Aging; Allergy; Angiogenesis; Branched amino acids; Bioenergetics;
Cancer; Fetal growth; Histamine; Hypersensitivity; Immune-privileged and
immune-responsive tissues; Mitochondria; Placenta; Taurine; Yin and Yang
of inflammation
ID SMALL-CELL-CARCINOMA; AGE-RELATED-CHANGES; NECROSIS-FACTOR-ALPHA; L-DOPA
DECARBOXYLASE; MAST-CELLS; OXIDATIVE STRESS; CAENORHABDITIS-ELEGANS;
AORTIC STIFFNESS; BLOOD-PRESSURE; IMMUNE-SYSTEM
AB Longevity and accumulation of multiple context-dependent signaling pathways of long-standing inflammation (antigen-load or oxidative stress) are the results of decreased/altered regulation of immunity and loss of control switch mechanisms that we defined as Yin and Yang of acute inflammation or immune surveillance. Chronic inflammation is initiated by immune disruptors-induced progressive changes in physiology and function of susceptible host tissues that lead to increased immune suppression and multistep disease processes including carcinogenesis. The interrelated multiple hypotheses that are presented for the first time in this article are extension of author's earlier series of 'accidental' discoveries on the role of inflammation in developmental stages of immune dysfunction toward tumorigenesis and angiogenesis. Detailed analyses of data on chronic diseases suggest that nearly all age-associated illnesses, generally categorized as 'mild' (e.g., increased allergies), 'moderate' (e.g., hypertension, colitis, gastritis, pancreatitis, emphysema) or 'severe' (e.g., accelerated neurodegenerative and autoimmune diseases or site-specific cancers and metastasis) are variations of hypersensitivity responses of tissues that are manifested as different diseases in immune-responsive or immune-privileged tissues. Continuous release/presence of low level histamine (subclinical) in circulation could contribute to sustained oxidative stress and induction of 'mild' or 'moderate' or 'severe' (immune tsunami) immune disorders in susceptible tissues. Site-specific cancers are proposed to be 'severe' (irreversible) forms of cumulative delayed hypersensitivity responses that would induce immunological chaos in favor of tissue growth in target tissues. Shared or special features of growth from fetus development into adulthood and aging processes and carcinogenesis are briefly compared with regard to energy requirements of highly complex function of Yin and Yang. Features of Yang (growth-promoting) arm of acute inflammation during fetus and cancer growth will be compared for consuming low energy from glycolysis (Warburg effect). Growth of fetus and cancer cells under hypoxic conditions and impaired mitochondrial energy requirements of tissues including metabolism of essential branched amino acids (e.g., val, leu, isoleu) will be compared for proposing a working model for future systematic research on cancer biology, prevention and therapy. Presentation of a working model provides insightful clues into bioenergetics that are required for fetus growth (absence of external threat and lack of high energy-demands of Yin events and parasite-like survival in host), normal growth in adulthood (balance in Yin and Yang processes) or disease processes and carcinogenesis (loss of balance in Yin-Yang). Future studies require focusing on dynamics and promotion of natural/inherent balance between Yin (tumoricidal) and Yang (tumorigenic) of effective immunity that develop after birth. Lawless growth of cancerous cells and loss of cell contact inhibition could partially be due to impaired mitochondria (mitophagy) that influence metabolism of branched chain amino acids for biosynthesis of structural proteins. The author invites interested scientists with diverse expertise to provide comments, confirm, dispute and question and/or expand and collaborate on many components of the proposed working model with the goal to better understand cancer biology for future designs of cost-effective research and clinical trials and prevention of cancer.
Initial events during oxidative stress-induced damages to DNA/RNA repair mechanisms and inappropriate expression of inflammatory mediators are potentially correctable, preventable or druggable, if future studies were to focus on systematic understanding of early altered immune response dynamics toward multistep chronic diseases and carcinogenesis.
C1 [Khatami, Mahin] NCI, NIH, Bethesda, MD 20892 USA.
RP Khatami, M (reprint author), NCI, NIH, Bethesda, MD 20892 USA.
EM mkgoodness@aol.com
FU National Eye Institute-NEI
FX The experimental studies on models of acute and chronic ocular
inflammatory diseases were established at the University of
Pennsylvania, School of Medicine, Department of Ophthalmology, Scheie
Eye Institute, laboratory of John H. Rockey, MD, Ph.D. with a supportive
team of scientists, funded by National Eye Institute-NEI. Analyses of
original data and recent hypotheses on the extension of our 'accidental'
discoveries were developed at the National Cancer Institute (NCI), the
National Institutes of Health (NIH) since 1998, despite heavy opposition
and denial of NCI decision makers to support the studies. Opinions
presented in this article are the author's views and not those of the
cancer establishment at NCI/NIH.
NR 224
TC 1
Z9 1
U1 8
U2 10
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 2001-1326
J9 CLIN TRANSL MED
JI Clin. Transl. Med.
PD AUG 23
PY 2016
VL 5
AR 35
DI 10.1186/s40169-016-0108-3
PG 23
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA EH7KH
UT WOS:000391951200001
PM 27558401
ER
PT J
AU Venugopalan, A
Lee, MJ
Niu, G
Medina-Echeverz, J
Tomita, Y
Lizak, MJ
Cultraro, CM
Simpson, RM
Chen, XY
Trepel, JB
Guha, U
AF Venugopalan, Abhilash
Lee, Min-Jung
Niu, Gang
Medina-Echeverz, Jose
Tomita, Yusuke
Lizak, Martin J.
Cultraro, Constance M.
Simpson, Robert Mark
Chen, Xiaoyuan
Trepel, Jane B.
Guha, Udayan
TI EGFR-targeted therapy results in dramatic early lung tumor regression
accompanied by imaging response and immune infiltration in EGFR mutant
transgenic mouse models
SO ONCOTARGET
LA English
DT Article
DE lung cancer; EGFR; TKI; imaging; immune-infiltration
ID GROWTH-FACTOR RECEPTOR; TYROSINE KINASE INHIBITOR; RANDOMIZED-TRIAL;
PHASE-III; CANCER; GEFITINIB; MUTATIONS; ADENOCARCINOMAS; CHEMOTHERAPY;
ERLOTINIB
AB Lung adenocarcinoma patients harboring kinase domain mutations in Epidermal growth factor receptor (EGFR) have significant clinical benefit from EGFR-targeted tyrosine kinase inhibitors (TKIs). Although a majority of patients experience clinical symptomatic benefit immediately, an objective response can only be demonstrated after 6-8 weeks of treatment. Evaluation of patient response by imaging shows that 30-40% of patients do not respond due to intrinsic resistance to these TKIs. We investigated immediate-early effects of EGFR-TKI treatment in mutant EGFR-driven transgenic mouse models by FDG-PET and MRI and correlated the effects on the tumor and the tumor microenvironment. Within 24 hours of erlotinib treatment we saw approximately 65% tumor regression in mice with TKI-sensitive EGFR(L858R) lung adenocarcinoma. However, mice with EGFR(L858R/T790M)-driven tumors did not respond to either erlotinib or afatinib monotherapy, but did show a significant tumor response to afatinib-cetuximab combination treatment. The imaging responses correlated with the inhibition of downstream EGFR signaling, increased apoptosis, and decreased proliferation in the tumor tissues. In EGFR(L858R)-driven tumors, we saw a significant increase in CD45(+) leukocytes, NK cells, dendritic cells, macrophages and lymphocytes, particularly CD8(+) T cells. In response to erlotinib, these dendritic cells and macrophages had significantly higher MHC class II expression, indicating increased antigen-presenting capabilities. Together, results of our study provide novel insight into the immediate-early therapeutic response to EGFR TKIs in vivo.
C1 [Venugopalan, Abhilash; Medina-Echeverz, Jose; Cultraro, Constance M.; Guha, Udayan] NCI, Thorac & Gastrointestinal Oncol Branch, Bethesda, MD 20892 USA.
[Lee, Min-Jung; Tomita, Yusuke; Trepel, Jane B.] NCI, Dev Therapeut Branch, Bethesda, MD 20892 USA.
[Niu, Gang; Chen, Xiaoyuan] Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed, Bethesda, MD USA.
[Lizak, Martin J.] NINDS, Mouse Imaging Facil, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
[Simpson, Robert Mark] NCI, Lab Canc Biol & Genet, Bethesda, MD 20892 USA.
RP Guha, U (reprint author), NCI, Thorac & Gastrointestinal Oncol Branch, Bethesda, MD 20892 USA.
EM udayan.guha@nih.gov
FU Intramural Research Program of the NIH / NCI / Center for Cancer
Research (CCR); Lung Cancer Research Foundation (LCRF)
FX This research was supported by the Intramural Research Program of the
NIH / NCI / Center for Cancer Research (CCR) and a Lung Cancer Research
Foundation (LCRF) grant (U. Guha).
NR 51
TC 2
Z9 2
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 AUG 23
PY 2016
VL 7
IS 34
BP 54137
EP 54156
DI 10.18632/oncotarget.11021
PG 20
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA DY9DY
UT WOS:000385435000005
PM 27494838
ER
PT J
AU Inaguma, S
Wang, ZF
Lasota, JP
Miettinen, MM
AF Inaguma, Shingo
Wang, Zengfeng
Lasota, Jerzy P.
Miettinen, Markku M.
TI Expression of neural cell adhesion molecule L1 (CD171) in
neuroectodermal and other tumors. An immunohistochemical study of 5155
tumors and critical evaluation of CD171 prognostic value in
gastrointestinal stromal tumors
SO ONCOTARGET
LA English
DT Article
DE CD171 (NCAM-L1, L1CAM); immunohistochemistry; neuroectodermal tumor;
gastrointestinal stromal tumor; mismatch repair deficiency
ID IMMUNOGLOBULIN SUPERFAMILY; ENDOMETRIAL CARCINOMAS; RECOGNITION
MOLECULES; MEDIATED RELEASE; AXON GUIDANCE; L1CAM; CANCER; L1-CAM;
NEUROBLASTOMA; RECEPTOR
AB The neural cell adhesion molecule L1 (CD171) is a multidomain type 1 membrane glycoprotein of the immunoglobulin superfamily important in the nervous system development, kidney morphogenesis, and maintenance of the immune system. Recent studies reported CD171 expression being associated with adverse clinical outcome in different types of cancer and there has been a growing interest in targeting this cell membrane molecule on neoplastic cells by chimeric antigen receptor redirected T lymphocytes or specific antibodies. Nevertheless, conflicting results regarding the prognostic value of CD171 expression in renal cell carcinomas and gastrointestinal stromal tumors were published. In this study, CD171 expression was immunohistochemically analyzed in 5155 epithelial, mesenchymal, melanocytic, and lymphohematopoietic tumors to assess its utility in diagnostic pathology and to pinpoint potential targets for CD171-targeting therapy. A newly developed anti-CD171 rabbit monoclonal antibody, clone 014, was selected from the panel of commercially available CD171 antibodies. Immunohistochemistry was performed using Leica Bond Max automation and multitumor blocks containing up to 60 tumor samples. CD171 was constitutively and strongly expressed in neuroectodermal tumors such as schwannoma, neuroblastoma, and paraganglioma, whereas other mesenchymal tumors including schwannoma mimics showed only rarely CD171 positivity. Frequent CD171-expression was also detected in ovarian serous carcinoma, malignant mesothelioma, and testicular embryonal carcinoma. CD171 immunohistochemistry may have some role in immunophenotypic differential diagnosis of neurogenic tumors and pinpointing potential candidates for anti-CD171 therapy. Though, because of its rare expression and lack of predictive value, CD171 is neither a diagnostic nor prognostic marker for gastrointestinal stromal tumors.
C1 [Inaguma, Shingo; Wang, Zengfeng; Lasota, Jerzy P.; Miettinen, Markku M.] NCI, Pathol Lab, Bldg 10, Bethesda, MD 20892 USA.
[Inaguma, Shingo] Aichi Med Univ, Dept Pathol, Sch Med, Nagakute, Aichi, Japan.
RP Inaguma, S (reprint author), NCI, Pathol Lab, Bldg 10, Bethesda, MD 20892 USA.; Inaguma, S (reprint author), Aichi Med Univ, Dept Pathol, Sch Med, Nagakute, Aichi, Japan.
EM inaguma@aichi-med-u.ac.jp
FU National Cancer Institute's intramural research program
FX This study was supported as a part of National Cancer Institute's
intramural research program. The authors have disclosed that they have
no relationships with, or financial interest in, any commercial
companies pertaining to this article.
NR 41
TC 0
Z9 0
U1 2
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 AUG 23
PY 2016
VL 7
IS 34
BP 55276
EP 55289
DI 10.18632/oncotarget.10527
PG 14
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA DY9DY
UT WOS:000385435000093
PM 27419370
ER
PT J
AU Fenerty, KE
Folio, LR
Patronas, NJ
Marte, JL
Gulley, JL
Heery, CR
AF Fenerty, Kathleen E.
Folio, Les R.
Patronas, Nicholas J.
Marte, Jennifer L.
Gulley, James L.
Heery, Christopher R.
TI Predicting clinical outcomes in chordoma patients receiving
immunotherapy: a comparison between volumetric segmentation and RECIST
SO BMC CANCER
LA English
DT Article
DE Chordoma; Volumetric; RECIST; Radiologic; Response criteria
ID RADIATION-THERAPY; RESPONSE CRITERIA; TUMOR RESPONSE; SOLID TUMORS; CT;
LESIONS; FRONTS
AB Background: The Response Evaluation Criteria in Solid Tumors (RECIST) are the current standard for evaluating disease progression or therapy response in patients with solid tumors. RECIST 1.1 calls for axial, longest-diameter (or perpendicular short axis of lymph nodes) measurements of a maximum of five tumors, which limits clinicians' ability to adequately measure disease burden, especially in patients with irregularly shaped tumors. This is especially problematic in chordoma, a disease for which RECIST does not always adequately capture disease burden because chordoma tumors are typically irregularly shaped and slow-growing. Furthermore, primary chordoma tumors tend to be adjacent to vital structures in the skull or sacrum that, when compressed, lead to significant clinical consequences.
Methods: Volumetric segmentation is a newer technology that allows tumor burden to be measured in three dimensions on either MR or CT. Here, we compared the ability of RECIST measurements and tumor volumes to predict clinical outcomes in a cohort of 21 chordoma patients receiving immunotherapy.
Results: There was a significant difference in radiologic time to progression Kaplan-Meier curves between clinical outcome groups using volumetric segmentation (P = 0.012) but not RECIST (P = 0.38). In several cases, changes in volume were earlier and more sensitive reflections of clinical status.
Conclusion: RECIST is a useful evaluation method when obvious changes are occurring in patients with chordoma. However, in many cases, RECIST does not detect small changes, and volumetric assessment was capable of detecting changes and predicting clinical outcome earlier than RECIST. Although this study was small and retrospective, we believe our results warrant further research in this area.
C1 [Fenerty, Kathleen E.; Heery, Christopher R.] NCI, Lab Tumor Immunol & Biol, Ctr Canc Res, NIH, 10 Ctr Dr,Room 13N208, Bethesda, MD 20892 USA.
[Folio, Les R.; Patronas, Nicholas J.] NCI, Canc Imaging Program, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA.
[Marte, Jennifer L.; Gulley, James L.] NCI, Genitourinary Malignancies Branch, NIH, Bethesda, MD 20892 USA.
RP Heery, CR (reprint author), NCI, Lab Tumor Immunol & Biol, Ctr Canc Res, NIH, 10 Ctr Dr,Room 13N208, Bethesda, MD 20892 USA.
EM heerycr@mail.nih.gov
FU Intramural Research Program of the Center for Cancer Research, National
Cancer Institute, National Institutes of Health
FX This research was supported by the Intramural Research Program of the
Center for Cancer Research, National Cancer Institute, National
Institutes of Health.
NR 18
TC 1
Z9 1
U1 1
U2 1
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 AUG 23
PY 2016
VL 16
AR 672
DI 10.1186/s12885-016-2699-x
PG 9
WC Oncology
SC Oncology
GA DX2JL
UT WOS:000384194700001
PM 27553491
ER
PT J
AU Felix, AS
Lenz, P
Pfeiffer, RM
Hewitt, SM
Morris, J
Patel, DA
Geller, B
Vacek, PM
Weaver, DL
Chicoine, RE
Shepherd, J
Mahmoudzadeh, AP
Wang, J
Fan, B
Malkov, S
Herschorn, SD
Johnson, JM
Cora, RL
Brinton, LA
Sherman, ME
Gierach, GL
AF Felix, Ashley S.
Lenz, Petra
Pfeiffer, Ruth M.
Hewitt, Stephen M.
Morris, Jennifer
Patel, Deesha A.
Geller, Berta
Vacek, Pamela M.
Weaver, Donald L.
Chicoine, Rachael E.
Shepherd, John
Mahmoudzadeh, Amir Pasha
Wang, Jeff
Fan, Bo
Malkov, Serghei
Herschorn, Sally D.
Johnson, Jason M.
Cora, Renata L.
Brinton, Louise A.
Sherman, Mark E.
Gierach, Gretchen L.
TI Relationships between mammographic density, tissue microvessel density,
and breast biopsy diagnosis
SO BREAST CANCER RESEARCH
LA English
DT Article
DE Mammographic density; Breast neoplasms; Angiogenesis; Pathology;
Lesional density
ID BACKGROUND PARENCHYMAL ENHANCEMENT; CANCER RISK; FIBROGLANDULAR TISSUE;
LOBULAR INVOLUTION; ADIPOSE-TISSUE; IN-SITU; ANGIOGENESIS; MRI; DISEASE;
IMPACT
AB Background: Women with high levels of mammographic density (MD) have a four-to six-fold increased risk of developing breast cancer; however, most neither have a prevalent tumor nor will they develop one. Magnetic resonance imaging (MRI) studies suggest that background parenchymal enhancement, an indicator of vascularity, is related to increased breast cancer risk. Correlations of microvessel density (MVD) in tissue, MD and biopsy diagnosis have not been defined, and we investigated these relationships among 218 women referred for biopsy.
Methods: MVD was determined by counting CD31-positive vessels in whole sections of breast biopsies in three representative areas; average MVD was transformed to approximate normality. Using digital mammograms, we quantified MD volume with single X-ray absorptiometry. We used linear regression to evaluate associations between MVD and MD adjusted for age and body mass index (BMI) overall, and stratified by biopsy diagnosis: cases (in situ or invasive cancer, n = 44) versus non-cases (non-proliferative or proliferative benign breast disease, n = 174). Logistic regression adjusted for age, BMI, and MD was used to calculate odds ratios (ORs) and 95 % confidence intervals (CIs) for associations between MVD and biopsy diagnosis. We also assessed whether the MVD-breast cancer association varied by MD.
Results: MVD and MD were not consistently associated. Higher MVD was significantly associated with higher odds of in situ/invasive disease (ORAdjusted = 1.69, 95 % CI = 1.17-2.44). MVD-breast cancer associations were strongest among women with greater non-dense volume.
Conclusions: Increased MVD in tissues is associated with breast cancer, independently of MD, consistent with MRI findings suggestive of its possible value as a radiological cancer biomarker.
C1 [Felix, Ashley S.; Pfeiffer, Ruth M.; Patel, Deesha A.; Cora, Renata L.; Brinton, Louise A.; Gierach, Gretchen L.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Felix, Ashley S.] NCI, Canc Prevent Fellowship Program, Canc Prevent Div, NIH, Bethesda, MD 20892 USA.
[Felix, Ashley S.] Ohio State Univ, Coll Publ Hlth, Div Epidemiol, 1841 Neil Ave,300C Cunz Hall, Columbus, OH 43210 USA.
[Lenz, Petra] Leidos Biomed Res Inc, Clin Res Directorate, Clin Monitoring Res Program, Frederick Natl Lab Canc Res, Frederick, MD USA.
[Hewitt, Stephen M.; Morris, Jennifer] NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Geller, Berta] Univ Vermont, Dept Family Med, Burlington, VT USA.
[Vacek, Pamela M.; Weaver, Donald L.] Univ Vermont, Dept Pathol, Burlington, VT 05405 USA.
[Chicoine, Rachael E.] Univ Vermont, Off Hlth Promot Res, Burlington, VT USA.
[Shepherd, John; Mahmoudzadeh, Amir Pasha; Wang, Jeff; Fan, Bo; Malkov, Serghei] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Wang, Jeff] Hokkaido Univ, Grad Sch Med, Sapporo, Hokkaido, Japan.
[Herschorn, Sally D.] Univ Vermont, Dept Radiol, Burlington, VT USA.
[Johnson, Jason M.] Univ Texas MD Anderson Canc Ctr, Dept Diagnost Radiol, Neuroradiol Sect, Houston, TX 77030 USA.
[Sherman, Mark E.] NCI, Div Canc Prevent, NIH, Bethesda, MD 20892 USA.
RP Felix, AS (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.; Felix, AS (reprint author), NCI, Canc Prevent Fellowship Program, Canc Prevent Div, NIH, Bethesda, MD 20892 USA.; Felix, AS (reprint author), Ohio State Univ, Coll Publ Hlth, Div Epidemiol, 1841 Neil Ave,300C Cunz Hall, Columbus, OH 43210 USA.
EM Felix.20@osu.edu
RI Gierach, Gretchen/E-1817-2016
OI Gierach, Gretchen/0000-0002-0165-5522
FU NCI NIH HHS [R01 CA166945]
NR 38
TC 0
Z9 0
U1 2
U2 3
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 AUG 23
PY 2016
VL 18
AR 88
DI 10.1186/s13058-016-0746-9
PG 12
WC Oncology
SC Oncology
GA DW1VK
UT WOS:000383430900001
PM 27552842
ER
PT J
AU Cossio, P
Hummer, G
Szabo, A
AF Cossio, Pilar
Hummer, Gerhard
Szabo, Attila
TI Kinetic Ductility and Force-Spike Resistance of Proteins from
Single-Molecule Force Spectroscopy
SO BIOPHYSICAL JOURNAL
LA English
DT Article
ID DYNAMICS SIMULATIONS; UNFOLDING PATHWAYS; ENERGY LANDSCAPES; ADHESION
BONDS; TITIN; DOMAIN; DEFORMATION; MICROSCOPY; DIFFUSION; UBIQUITIN
AB Ductile materials can absorb spikes in mechanical force, whereas brittle ones fail catastrophically. Here we develop a theory to quantify the kinetic ductility of single molecules from force spectroscopy experiments, relating force-spike resistance to the differential responses of the intact protein and the unfolding transition state to an applied mechanical force. We introduce a class of unistable one-dimensional potential surfaces that encompass previous models as special cases and continuously cover the entire range from ductile to brittle. Compact analytic expressions for force-dependent rates and rupture-force distributions allow us to analyze force-clamp and force-ramp pulling experiments. We find that the force-transmitting protein domains of filamin and titin are kinetically ductile when pulled from their two termini, making them resistant to force spikes. For the mechanostable muscle protein titin, a highly ductile model reconciles data over 10 orders of magnitude in force loading rate from experiment and simulation.
C1 [Cossio, Pilar; Hummer, Gerhard] Max Planck Inst Biophys, Dept Theoret Biophys, Frankfurt, Germany.
[Szabo, Attila] Natl Inst Diabet & Digest & Kidney Dis, Lab Chem Phys, NIH, Bethesda, MD USA.
RP Hummer, G (reprint author), Max Planck Inst Biophys, Dept Theoret Biophys, Frankfurt, Germany.
EM gerhard.hummer@biophys.mpg.de
RI Hummer, Gerhard/A-2546-2013; Szabo, Attila/H-3867-2012
OI Hummer, Gerhard/0000-0001-7768-746X;
FU Max Planck Society; Intramural Research Program of the National
Institute of Diabetes and Digestive and Kidney Diseases, National
Institutes of Health
FX P.C. and G.H. were supported by the Max Planck Society; and A.S. was
supported by the Intramural Research Program of the National Institute
of Diabetes and Digestive and Kidney Diseases, National Institutes of
Health.
NR 47
TC 0
Z9 0
U1 8
U2 8
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 AUG 23
PY 2016
VL 111
IS 4
BP 832
EP 840
DI 10.1016/j.bpj.2016.05.054
PG 9
WC Biophysics
SC Biophysics
GA DU3GR
UT WOS:000382099300016
PM 27558726
ER
PT J
AU Manago, F
Mereu, M
Mastwal, S
Mastrogiacomo, R
Scheggia, D
Emanuele, M
De Luca, MA
Weinberger, DR
Wang, KH
Papaleo, F
AF Manago, Francesca
Mereu, Maddalena
Mastwal, Surjeet
Mastrogiacomo, Rosa
Scheggia, Diego
Emanuele, Marco
De Luca, Maria A.
Weinberger, Daniel R.
Wang, Kuan Hong
Papaleo, Francesco
TI Genetic Disruption of Arc/Arg3.1 in Mice Causes Alterations in Dopamine
and Neurobehavioral Phenotypes Related to Schizophrenia
SO CELL REPORTS
LA English
DT Article
ID VENTRAL TEGMENTAL AREA; AMPHETAMINE-INDUCED ACTIVITY; MEDIAL PREFRONTAL
CORTEX; IMMEDIATE-EARLY GENE; TEMPORAL-ORDER; PREPULSE INHIBITION;
SYNAPTIC PLASTICITY; RECOGNITION MEMORY; NUCLEUS-ACCUMBENS; PYRAMIDAL
NEURONS
AB Human genetic studies have recently suggested that the postsynaptic activity-regulated cytoskeleton-associated protein (Arc) complex is a convergence signal for several genes implicated in schizophrenia. However, the functional significance of Arc in schizophrenia-related neurobehavioral phenotypes and brain circuits is unclear. Here, we find that, consistent with schizophrenia-related phenotypes, disruption of Arc in mice produces deficits in sensorimotor gating, cognitive functions, social behaviors, and amphetamine-induced psychomotor responses. Furthermore, genetic disruption of Arc leads to concomitant hypoactive mesocortical and hyperactive mesostriatal dopamine pathways. Application of a D1 agonist to the prefrontal cortex or a D2 antagonist in the ventral striatumrescues Arc-dependent cognitive or psychomotor abnormalities, respectively. Our findings demonstrate a role for Arc in the regulation of dopaminergic neurotransmission and related behaviors. The results also provide initial biological support implicating Arc in dopaminergic and behavioral abnormalities related to schizophrenia.
C1 [Manago, Francesca; Mastrogiacomo, Rosa; Scheggia, Diego; Emanuele, Marco; Papaleo, Francesco] Ist Italiano Tecnol, Dept Neurosci & Brain Technol, Via Morego 30, I-16163 Genoa, Italy.
[Mereu, Maddalena] Univ Padua, Dipartimento Sci Farmaco, Largo Meneghetti 2, I-35131 Padua, Italy.
[Mastwal, Surjeet; Wang, Kuan Hong] NIMH, Unit Neural Circuits & Adapt Behav, Clin & Translat Neurosci Branch, Bethesda, MD 20892 USA.
[De Luca, Maria A.] Univ Cagliari, Dept Biomed Sci, I-09124 Cagliari, Italy.
[Weinberger, Daniel R.] Johns Hopkins Univ, Lieber Inst Brain Dev, Med Campus, Baltimore, MD 21205 USA.
[Weinberger, Daniel R.] Johns Hopkins Sch Med, Dept Psychiat, Baltimore, MD 21205 USA.
[Weinberger, Daniel R.] Johns Hopkins Sch Med, Dept Neurol, Baltimore, MD 21205 USA.
[Weinberger, Daniel R.] Johns Hopkins Sch Med, Dept Neurosci, Baltimore, MD 21205 USA.
[Weinberger, Daniel R.] Johns Hopkins Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD 21205 USA.
RP Papaleo, F (reprint author), Ist Italiano Tecnol, Dept Neurosci & Brain Technol, Via Morego 30, I-16163 Genoa, Italy.; Wang, KH (reprint author), NIMH, Unit Neural Circuits & Adapt Behav, Clin & Translat Neurosci Branch, Bethesda, MD 20892 USA.
EM wkuan@mail.nih.gov; francesco.papaleo@iit.it
RI Wang, Kuan Hong/J-1150-2016;
OI Wang, Kuan Hong/0000-0002-2249-5417; Papaleo,
Francesco/0000-0002-6326-0657
FU Istituto Italiano di Tecnologia, Marie Curie grant [268247]; Italian
Ministry of Health [GR-2010-2315883]; NARSAD Independent Investigator
grant [23234]; Intramural Research Program of the National Institute of
Mental Health [ZIA MH002897]
FX We thank Dr. G. Tanda, Dr. R. Gainetdinov, Dr. M. Morini, D. Cantatore,
and C. Chiabrera for suggestions and technical assistance. We thank Dr.
S. Tonegawa for donating the Arc mutant breeders. This research was
supported by the Istituto Italiano di Tecnologia, Marie Curie grant
268247, Italian Ministry of Health grant GR-2010-2315883, and 2015
NARSAD Independent Investigator grant 23234 (to F.P.) and by the
Intramural Research Program of the National Institute of Mental Health
(ZIA MH002897 to D.R.W. and K.H.W.).
NR 72
TC 1
Z9 1
U1 6
U2 6
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 AUG 23
PY 2016
VL 16
IS 8
BP 2116
EP 2128
DI 10.1016/j.celrep.2016.07.044
PG 13
WC Cell Biology
SC Cell Biology
GA DU6FQ
UT WOS:000382310100009
PM 27524619
ER
PT J
AU Casagrande, SS
Menke, A
Cowie, CC
AF Casagrande, Sarah S.
Menke, Andy
Cowie, Catherine C.
TI Cardiovascular Risk Factors of Adults Age 20-49 Years in the United
States, 1971-2012: A Series of Cross-Sectional Studies
SO PLOS ONE
LA English
DT Article
ID OBESITY; HEALTH; ASSOCIATION; BALTIMORE; EPIDEMIC; MARYLAND; TRENDS; BMI
AB Background
The health of younger adults in the U.S. has important public health and economic-related implications. However, previous literature is insufficient to fully understand how the health of this group has changed over time. This study examined generational differences in cardiovascular risk factors of younger adults over the past 40 years.
Methods
Data were from 6 nationally representative cross-sectional National Health and Nutrition Examination Surveys (1971-2012; N = 44,670). Participants were adults age 20-49 years who self-reported sociodemographic characteristics and health conditions, and had examination/laboratory measures for hypertension, hyperlipidemia, diabetes, obesity, and chronic kidney disease. Prevalences of sociodemographic characteristics and health status were determined by study period. Logistic regression was used to determine the odds [odds ratio (OR), 95% confidence interval] of health conditions by study period: models adjusted only for age, sex, and race, and fully adjusted models additionally adjusted for socioeconomic characteristics, smoking, BMI, diabetes, and/or hypertension (depending on the outcome) were assessed.
Results
Participants in 2009-2012 were significantly more likely to be obese and have diabetes compared to those in 1971-1975 (OR = 4.98, 3.57-6.97; OR = 3.49, 1.59-7.65, respectively, fully adjusted). Participants in 2009-2012 vs. 1988-1994 were significantly more likely to have had hypertension but uncontrolled hypertension was significantly less likely (OR = 0.67, 0.52-0.86, fully adjusted). There was no difference over time for high cholesterol, but uncontrolled high cholesterol was significantly less likely in 2009-2012 vs. 1988-1994 (OR = 0.80, 0.68-0.94, fully adjusted). The use of hypertensive and cholesterol medications increased while chronic kidney and cardiovascular diseases were relatively stable.
Conclusions
Cardiovascular risk factors of younger U.S. adults have worsened over the past 40 years, but treatment for hypertension and high cholesterol has improved. The sub-optimal and worsening health in younger adults may have a substantial impact on health care utilization and costs, and should be considered when developing health care practices.
C1 [Casagrande, Sarah S.; Menke, Andy] Social & Sci Syst Inc, Publ Hlth Res, Silver Spring, MD 20910 USA.
[Cowie, Catherine C.] NIDDK, Div Diabet Endocrinol & Metab Dis, Bethesda, MD 20892 USA.
RP Casagrande, SS (reprint author), Social & Sci Syst Inc, Publ Hlth Res, Silver Spring, MD 20910 USA.
EM scasagrande@s-3.com
FU National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
[GS-10F-0381L]
FX The National Institute of Diabetes and Digestive and Kidney Diseases
(NIDDK) (GS-10F-0381L) funded NHANES and oversaw its conduct and
reporting with regard to diabetes-related data. As employees NIDDK (C.
Cowie) or contractors of NIDDK (Social & Scientific Systems, Inc.; S.
Casagrande, A. Menke), the authors had a direct role in the design and
interpretation of the secondary analysis and the decision to submit the
manuscript for publication.
NR 51
TC 0
Z9 0
U1 15
U2 15
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 AUG 23
PY 2016
VL 11
IS 8
AR e0161770
DI 10.1371/journal.pone.0161770
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DT8TR
UT WOS:000381768800075
PM 27552151
ER
PT J
AU Liberman, Z
Woodward, AL
Sullivan, KR
Kinzler, KD
AF Liberman, Zoe
Woodward, Amanda L.
Sullivan, Kathleen R.
Kinzler, Katherine D.
TI Early emerging system for reasoning about the social nature of food
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE food; social cognition; infancy; cognitive development; disgust
ID CHILDS CONCEPTION; CONTAMINATION SENSITIVITY; INDUCTIVE INFERENCES;
INFANTS GENERALIZE; SHAPE SIMILARITY; YOUNG-CHILDREN; SHARED LABELS;
PREFERENCES; EAT; CONSUMPTION
AB Selecting appropriate foods is a complex and evolutionarily ancient problem, yet past studies have revealed little evidence of adaptations present in infancy that support sophisticated reasoning about perceptual properties of food. We propose that humans have an early-emerging system for reasoning about the social nature of food selection. Specifically, infants' reasoning about food choice is tied to their thinking about agents' intentions and social relationships. Whereas infants do not expect people to like the same objects, infants view food preferences as meaningfully shared across individuals. Infants' reasoning about food preferences is fundamentally social: They generalize food preferences across individuals who affiliate, or who speak a common language, but not across individuals who socially disengage or who speak different languages. Importantly, infants' reasoning about food preferences is flexibly calibrated to their own experiences: Tests of bilingual babies reveal that an infant's sociolinguistic background influences whether she will constrain her generalization of food preferences to people who speak the same language. Additionally, infants' systems for reasoning about food is differentially responsive to positive and negative information. Infants generalize information about food disgust across all people, regardless of those people's social identities. Thus, whereas food preferences are seen as embedded within social groups, disgust is interpreted as socially universal, which could help infants avoid potentially dangerous foods. These studies reveal an early-emerging system for thinking about food that incorporates social reasoning about agents and their relationships, and allows infants to make abstract, flexible, adaptive inferences to interpret others' food choices.
C1 [Liberman, Zoe; Woodward, Amanda L.; Sullivan, Kathleen R.; Kinzler, Katherine D.] Univ Chicago, Dept Psychol, Chicago, IL 60642 USA.
[Sullivan, Kathleen R.] NIH, Off Res Womens Hlth, Bldg 10, Bethesda, MD 20892 USA.
[Kinzler, Katherine D.] Cornell Univ, Dept Psychol, Ithaca, NY 14853 USA.
[Kinzler, Katherine D.] Cornell Univ, Dept Human Dev, Ithaca, NY 14853 USA.
RP Liberman, Z (reprint author), Univ Chicago, Dept Psychol, Chicago, IL 60642 USA.
EM zoeliberman@uchicago.edu
FU NIH [R01 HD070890]; National Science Foundation Graduate Research
Fellowship Program
FX We thank Kristin Shutts for extremely helpful conversations about the
intellectual direction of this project, and Alex Shaw and Susan
Goldin-Meadow for comments on a previous version of this manuscript.
This research was supported by NIH Grant R01 HD070890 (to K.D.K.) and by
a National Science Foundation Graduate Research Fellowship Program (to
Z.L.).
NR 85
TC 0
Z9 0
U1 5
U2 7
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 AUG 23
PY 2016
VL 113
IS 34
BP 9480
EP 9485
DI 10.1073/pnas.1605456113
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DT9ZK
UT WOS:000381860800042
PM 27503878
ER
PT J
AU Wang, W
Nguyen, LTT
Burlak, C
Chegini, F
Guo, F
Chataway, T
Ju, SL
Fisher, OS
Miller, DW
Datta, D
Wu, F
Wu, CX
Landeru, A
Wells, JA
Cookson, MR
Boxer, MB
Thomas, CJ
Gai, WP
Ringe, D
Petsko, GA
Hoang, QQ
AF Wang, Wei
Nguyen, Linh T. T.
Burlak, Christopher
Chegini, Fariba
Guo, Feng
Chataway, Tim
Ju, Shulin
Fisher, Oriana S.
Miller, David W.
Datta, Debajyoti
Wu, Fang
Wu, Chun-Xiang
Landeru, Anuradha
Wells, James A.
Cookson, Mark R.
Boxer, Matthew B.
Thomas, Craig J.
Gai, Wei Ping
Ringe, Dagmar
Petsko, Gregory A.
Hoang, Quyen Q.
TI Caspase-1 causes truncation and aggregation of the Parkinson's
disease-associated protein alpha-synuclein
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE synuclein; Parkinson's disease; caspase; inflammasome; aggregation
ID TRAUMATIC BRAIN-INJURY; GROWTH-FACTOR-ALPHA; CEREBROSPINAL-FLUID; MOUSE
MODEL; IN-VIVO; NEURODEGENERATION; INTERLEUKIN-1-BETA;
NEUROINFLAMMATION; INFLAMMATION; PATHOGENESIS
AB The aggregation of alpha-synuclein (aSyn) leading to the formation of Lewy bodies is the defining pathological hallmark of Parkinson's disease (PD). Rare familial PD-associated mutations in aSyn render it aggregation-prone; however, PD patients carrying wild type (WT) aSyn also have aggregated aSyn in Lewy bodies. The mechanisms by which WT aSyn aggregates are unclear. Here, we report that inflammation can play a role in causing the aggregation of WT aSyn. We show that activation of the inflammasome with known stimuli results in the aggregation of aSyn in a neuronal cell model of PD. The insoluble aggregates are enriched with truncated aSyn as found in Lewy bodies of the PD brain. Inhibition of the inflammasome enzyme caspase-1 by chemical inhibition or genetic knockdown with shRNA abated aSyn truncation. In vitro characterization confirmed that caspase-1 directly cleaves aSyn, generating a highly aggregation-prone species. The truncation-induced aggregation of aSyn is toxic to neuronal culture, and inhibition of caspase-1 by shRNA or a specific chemical inhibitor improved the survival of a neuronal PD cell model. This study provides a molecular link for the role of inflammation in aSyn aggregation, and perhaps in the pathogenesis of sporadic PD as well.
C1 [Wang, Wei; Nguyen, Linh T. T.; Wu, Chun-Xiang; Landeru, Anuradha; Hoang, Quyen Q.] Indiana Univ Sch Med, Dept Biochem & Mol Biol, Indianapolis, IN 46202 USA.
[Wang, Wei; Nguyen, Linh T. T.; Wu, Chun-Xiang; Landeru, Anuradha; Hoang, Quyen Q.] Indiana Univ Sch Med, Stark Neurosci Res Inst, Indianapolis, IN 46202 USA.
[Burlak, Christopher] Univ Minnesota, Dept Surg, Schulze Diabet Inst, Box 242 UMHC, Minneapolis, MN 55455 USA.
[Chegini, Fariba; Guo, Feng; Chataway, Tim; Gai, Wei Ping] Flinders Univ S Australia, Dept Human Physiol, Ctr Neurosci, Adelaide, SA 5001, Australia.
[Ju, Shulin; Fisher, Oriana S.; Wu, Fang; Ringe, Dagmar; Petsko, Gregory A.] Brandeis Univ, Dept Chem, Rosenstiel Basic Med Sci Res Ctr, Waltham, MA 02454 USA.
[Ju, Shulin; Fisher, Oriana S.; Wu, Fang; Ringe, Dagmar; Petsko, Gregory A.] Brandeis Univ, Dept Biochem, Rosenstiel Basic Med Sci Res Ctr, Waltham, MA 02454 USA.
[Miller, David W.; Cookson, Mark R.] NIH, Neurogenet Lab, Bldg 10, Bethesda, MD 20892 USA.
[Datta, Debajyoti; Wells, James A.] Univ Calif San Francisco, Dept Pharmaceut Chem, San Francisco, CA 94143 USA.
[Wells, James A.] Univ Calif San Francisco, Dept Cellular & Mol Physiol, San Francisco, CA 94143 USA.
[Boxer, Matthew B.; Thomas, Craig J.] NIH, Natl Ctr Adv Translat Sci, Chem Genom Ctr, Bldg 10, Bethesda, MD 20892 USA.
[Ringe, Dagmar; Petsko, Gregory A.] Harvard Med Sch, Dept Neurol, Cambridge, MA 02139 USA.
[Ringe, Dagmar; Petsko, Gregory A.] Brigham & Womens Hosp, Ctr Neurol Dis, Boston, MA 02116 USA.
[Hoang, Quyen Q.] Indiana Univ Sch Med, Dept Neurol, Indianapolis, IN 46202 USA.
[Ju, Shulin] Wright State Univ, Dept Biol Sci, Dayton, OH 45435 USA.
[Fisher, Oriana S.] Northwestern Univ, Dept Mol Biosci, Evanston, IL 60208 USA.
[Wu, Fang; Petsko, Gregory A.] Univ Calif Berkeley, Dept Mol & Cell Biol, Calif Inst Quantitat Biol, 229 Stanley Hall, Berkeley, CA 94720 USA.
[Petsko, Gregory A.; Hoang, Quyen Q.] Weill Cornell Med Coll, Dept Neurol & Neurosci, New York, NY 10065 USA.
RP Hoang, QQ (reprint author), Indiana Univ Sch Med, Dept Biochem & Mol Biol, Indianapolis, IN 46202 USA.; Hoang, QQ (reprint author), Indiana Univ Sch Med, Stark Neurosci Res Inst, Indianapolis, IN 46202 USA.; Petsko, GA (reprint author), Brandeis Univ, Dept Chem, Rosenstiel Basic Med Sci Res Ctr, Waltham, MA 02454 USA.; Petsko, GA (reprint author), Brandeis Univ, Dept Biochem, Rosenstiel Basic Med Sci Res Ctr, Waltham, MA 02454 USA.; Petsko, GA (reprint author), Harvard Med Sch, Dept Neurol, Cambridge, MA 02139 USA.; Petsko, GA (reprint author), Brigham & Womens Hosp, Ctr Neurol Dis, Boston, MA 02116 USA.; Hoang, QQ (reprint author), Indiana Univ Sch Med, Dept Neurol, Indianapolis, IN 46202 USA.; Petsko, GA (reprint author), Univ Calif Berkeley, Dept Mol & Cell Biol, Calif Inst Quantitat Biol, 229 Stanley Hall, Berkeley, CA 94720 USA.; Petsko, GA; Hoang, QQ (reprint author), Weill Cornell Med Coll, Dept Neurol & Neurosci, New York, NY 10065 USA.
EM gpetsko@med.cornell.edu; qqhoang@iu.edu
RI Wells, Jim/O-9854-2016
FU Community Fast Track grant from Michael J. Fox Foundation; National
Institutes of Health Grants [1R21NS079881-01, 5R01GM111639]; Indiana
University School of Medicine Biomedical Research Grant; Indiana
University-Purdue University Indianapolis Research Support Funds Grant;
Fidelity Biosciences Research Initiative; Ellison Medical Foundation;
McKnight Endowment for Neuroscience; Molecular Libraries Initiative of
the National Institutes of Health Roadmap for Medical Research;
Intramural Research Program of the National Human Genome Research
Institute, National Institutes of Health; Intramural Research Program of
the National Institute on Aging, National Institutes of Health
FX We thank S. Lindquist for the yeast expression vectors of aSyn, and Z.
Y. Z. Zhang and L. Chen for their generous support and access to the
Chemical Genomics Core Facility at Indiana University. Q.Q.H., D.R., and
G.A.P. were supported through a Community Fast Track grant from the
Michael J. Fox Foundation. Q.Q.H. was also supported by National
Institutes of Health Grants 1R21NS079881-01 and 5R01GM111639, an Indiana
University School of Medicine Biomedical Research Grant, and an Indiana
University-Purdue University Indianapolis Research Support Funds Grant.
D.R. and G.A.P. also acknowledge support from the Fidelity Biosciences
Research Initiative (with much useful discussion from Dr. S. Weninger)
and early support from the Ellison Medical Foundation and the McKnight
Endowment for Neuroscience. M.B.B. and C.J.T. acknowledge support from
the Molecular Libraries Initiative of the National Institutes of Health
Roadmap for Medical Research and the Intramural Research Program of the
National Human Genome Research Institute, National Institutes of Health.
This research was supported in part by the Intramural Research Program
of the National Institute on Aging, National Institutes of Health.
NR 50
TC 0
Z9 0
U1 8
U2 9
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 AUG 23
PY 2016
VL 113
IS 34
BP 9587
EP 9592
DI 10.1073/pnas.1610099113
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DT9ZK
UT WOS:000381860800060
ER
PT J
AU Brinkmeyer-Langford, C
Balog-Alvarez, C
Cai, JJ
Davis, BW
Kornegay, JN
AF Brinkmeyer-Langford, Candice
Balog-Alvarez, Cynthia
Cai, James J.
Davis, Brian W.
Kornegay, Joe N.
TI Genome-wide association study to identify potential genetic modifiers in
a canine model for Duchenne muscular dystrophy
SO BMC GENOMICS
LA English
DT Article
DE Muscular dystrophy; Duchenne muscular dystrophy; DMD; Golden retriever
muscular dystrophy; GRMD; Modifier; Linear mixed-model analysis; Gene
expression
ID READING-FRAME RULE; NONSENSE MUTATION; POPULATION STRATIFICATION;
MESSENGER-RNA; DOGS; DISEASE; EXPRESSION; MUSCLE; DMD; EXON
AB Background: Duchenne muscular dystrophy (DMD) causes progressive muscle degeneration, cardiomyopathy and respiratory failure in approximately 1/5,000 boys. Golden Retriever muscular dystrophy (GRMD) resembles DMD both clinically and pathologically. Like DMD, GRMD exhibits remarkable phenotypic variation among affected dogs, suggesting the influence of modifiers. Understanding the role(s) of genetic modifiers of GRMD may identify genes and pathways that also modify phenotypes in DMD and reveal novel therapies. Therefore, our objective in this study was to identify genetic modifiers that affect discrete GRMD phenotypes.
Results: We performed a linear mixed-model (LMM) analysis using 16 variably-affected dogs from our GRMD colony (8 dystrophic, 8 non-dystrophic). All of these dogs were either full or half-siblings, and phenotyped for 19 objective, quantitative biomarkers at ages 6 and 12 months. Each biomarker was individually assessed. Gene expression profiles of 59 possible candidate genes were generated for two muscle types: the cranial tibialis and medial head of the gastrocnemius. SNPs significantly associated with GRMD biomarkers were identified on multiple chromosomes (including the X chromosome). Gene expression levels for candidate genes located near these SNPs correlated with biomarker values, suggesting possible roles as GRMD modifiers.
Conclusions: The results of this study enhance our understanding of GRMD pathology and represent a first step toward the characterization of GRMD modifiers that may be relevant to DMD pathology. Such modifiers are likely to be useful for DMD treatment development based on their relationships to GRMD phenotypes.
C1 [Brinkmeyer-Langford, Candice; Balog-Alvarez, Cynthia; Cai, James J.; Kornegay, Joe N.] Texas A&M Univ, Dept Vet Integrat Biosci, College Stn, TX USA.
[Davis, Brian W.] NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA.
RP Brinkmeyer-Langford, C (reprint author), Texas A&M Univ, Dept Vet Integrat Biosci, College Stn, TX USA.
EM cbrinkmeyer@cvm.tamu.edu
OI Cai, James/0000-0002-8081-6725
FU NINDS grant [1U24NS059696-01A1]; Co-operative Program in Translational
Research: Proposal for Establishment of the National Center for Canine
Models of Duchenne Muscular Dystrophy; Muscular Dystrophy Association
Infrastructure grant
FX NINDS grant 1U24NS059696-01A1, the Co-operative Program in Translational
Research: Proposal for Establishment of the National Center for Canine
Models of Duchenne Muscular Dystrophy, and a Muscular Dystrophy
Association Infrastructure grant to the Translational Research Advisory
Committee (J.N.K.).
NR 82
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 1471-2164
J9 BMC GENOMICS
JI BMC Genomics
PD AUG 22
PY 2016
VL 17
AR 665
DI 10.1186/s12864-016-2948-z
PG 15
WC Biotechnology & Applied Microbiology; Genetics & Heredity
SC Biotechnology & Applied Microbiology; Genetics & Heredity
GA DY3GT
UT WOS:000384979500002
PM 27549615
ER
PT J
AU Guerard, F
Lee, YS
Baidoo, K
Gestin, JF
Brechbiel, MW
AF Guerard, Francois
Lee, Yong-Sok
Baidoo, Kwamena
Gestin, Jean-Francois
Brechbiel, Martin W.
TI Unexpected Behavior of the Heaviest Halogen Astatine in the Nucleophilic
Substitution of Aryliodonium Salts
SO CHEMISTRY-A EUROPEAN JOURNAL
LA English
DT Article
DE astatine; halogenation; iodonium salts; nucleophilic substitution;
radiopharmaceuticals
ID DIARYLIODONIUM SALTS; RADIOFLUORINATION; CHEMISTRY; THERAPY; TOSYLATES;
SOLVENTS; ARENES; IODINE; ARYL
AB Aryliodonium salts have become precursors of choice for the synthesis of F-18-labeled tracers for nuclear imaging. However, little is known on the reactivity of these compounds with heavy halides, that is, radioiodide and astatide, at the radiotracer scale. In the first comparative study of radiohalogenation of aryliodonium salts with I-125(-) and At-211(-), initial experiments on a model compound highlight the higher reactivity of astatide compared to iodide, which could not be anticipated from the trends previously observed within the halogen series. Kinetic studies indicate a significant difference in activation energy (E-a=23.5 and 17.1kcalmol(-1) with I-125(-) and At-211(-), respectively). Quantum chemical calculations suggest that astatination occurs via the monomeric form of an iodonium complex whereas iodination occurs via a heterodimeric iodonium intermediate. The good to excellent regioselectivity of halogenation and high yields achieved with diversely substituted aryliodonium salts indicate that this class of compounds is a promising alternative to the stannane chemistry currently used for heavy radiohalogen labeling of tracers in nuclear medicine.
C1 [Guerard, Francois; Baidoo, Kwamena; Brechbiel, Martin W.] NCI, Radioimmune & Inorgan Chem Sect, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA.
[Guerard, Francois; Gestin, Jean-Francois] Univ Nantes, INSERM, U892, CNRS,UMR6299, Nantes, France.
[Lee, Yong-Sok] NIH, Ctr Mol Modeling, Div Computat Biosci, Ctr Informat Technol, Bldg 10, Bethesda, MD 20892 USA.
RP Guerard, F (reprint author), NCI, Radioimmune & Inorgan Chem Sect, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA.; Guerard, F (reprint author), Univ Nantes, INSERM, U892, CNRS,UMR6299, Nantes, France.
EM francois.guerard@univ-nantes.fr
OI Guerard, Francois/0000-0001-9795-2785
FU Intramural Research Program of the NIH, National Cancer Institute,
Center for Cancer Research and Center for Information Technology; French
National Agency for Research, called "Investissements d'Avenir" IRON
Labex [ANR-11-LABX-0018-01]; ArronaxPlus Equipex [ANR-11-EQPX-0004]
FX This research was supported by the Intramural Research Program of the
NIH, National Cancer Institute, Center for Cancer Research and Center
for Information Technology and in part by grants from the French
National Agency for Research, called "Investissements d'Avenir" IRON
Labex (no. ANR-11-LABX-0018-01) and ArronaxPlus Equipex (no.
ANR-11-EQPX-0004). The quantum chemical study utilized PC/linux clusters
at the center for Molecular Modeling of the National Institutes of
Health (http://cit.nih.gov). Lawrence Szajek, NIH, CC is thanked for his
cyclotron operations and irradiation of bismuth targets for the
production of 211At. Professor Vanelle is thanked for the
input on radical mechanism investigations.
NR 49
TC 0
Z9 0
U1 9
U2 9
PU WILEY-V C H VERLAG GMBH
PI WEINHEIM
PA POSTFACH 101161, 69451 WEINHEIM, GERMANY
SN 0947-6539
EI 1521-3765
J9 CHEM-EUR J
JI Chem.-Eur. J.
PD AUG 22
PY 2016
VL 22
IS 35
BP 12332
EP 12339
DI 10.1002/chem.201600922
PG 8
WC Chemistry, Multidisciplinary
SC Chemistry
GA DV4DX
UT WOS:000382876500017
PM 27305065
ER
PT J
AU Hager, A
Wu, MX
Wang, HC
Brown, NW
Shears, SB
Veiga, N
Fiedler, D
AF Hager, Anastasia
Wu, Mingxuan
Wang, Huanchen
Brown, Nathaniel W., Jr.
Shears, Stephen B.
Veiga, Nicolas
Fiedler, Dorothea
TI Cellular Cations Control Conformational Switching of Inositol
Pyrophosphate Analogues
SO CHEMISTRY-A EUROPEAN JOURNAL
LA English
DT Article
DE biological activity; conformation analysis; phosphorylation;
protonation; signal transduction
ID DIPHOSPHOINOSITOL-POLYPHOSPHATE PHOSPHOHYDROLASES; MYOINOSITOL
HEXAKISPHOSPHATE; P-31 NMR; PROTEIN PYROPHOSPHORYLATION;
SACCHAROMYCES-CEREVISIAE; PH MICRODOMAINS; TELOMERE LENGTH; KINASE;
PENTAKISPHOSPHATE; METABOLISM
AB The inositol pyrophosphate messengers (PP-InsPs) are emerging as an important class of cellular regulators. These molecules have been linked to numerous biological processes, including insulin secretion and cancer cell migration, but how they trigger such a wide range of cellular responses has remained unanswered in many cases. Here, we show that the PP-InsPs exhibit complex speciation behaviour and propose that a unique conformational switching mechanism could contribute to their multifunctional effects. We synthesised non-hydrolysable bisphosphonate analogues and crystallised the analogues in complex with mammalian PPIP5K2 kinase. Subsequently, the bisphosphonate analogues were used to investigate the protonation sequence, metal-coordination properties, and conformation in solution. Remarkably, the presence of potassium and magnesium ions enabled the analogues to adopt two different conformations near physiological pH. Understanding how the intrinsic chemical properties of the PP-InsPs can contribute to their complex signalling outputs will be essential to elucidate their regulatory functions.
C1 [Brown, Nathaniel W., Jr.; Fiedler, Dorothea] Leibniz Inst Mol Pharmacol, Robert Rossle Str 10, D-13125 Berlin, Germany.
[Hager, Anastasia; Wu, Mingxuan; Brown, Nathaniel W., Jr.; Fiedler, Dorothea] Princeton Univ, Dept Chem, Washington Rd, Princeton, NJ 08544 USA.
[Wang, Huanchen; Shears, Stephen B.] NIH, Inositol Signaling Grp, Res Triangle Pk, NC 27709 USA.
[Veiga, Nicolas] Univ Republica, Fac Quim, Catedra Quim Inorgan, Dept Estrella Campos, CC 1157, Montevideo, Uruguay.
RP Fiedler, D (reprint author), Leibniz Inst Mol Pharmacol, Robert Rossle Str 10, D-13125 Berlin, Germany.; Fiedler, D (reprint author), Princeton Univ, Dept Chem, Washington Rd, Princeton, NJ 08544 USA.; Veiga, N (reprint author), Univ Republica, Fac Quim, Catedra Quim Inorgan, Dept Estrella Campos, CC 1157, Montevideo, Uruguay.
EM nveiga@fq.edu.uy; fiedler@fmp-berlin.de
FU Deutsche Forschungsgemeinschaft (DFG); NIH [DP2 CA186753]; Sidney Kimmel
Foundation; Rita Allen Foundation; Princeton University
FX We thank Dr. Istvan Pelczer, Ken Conover, and Dr. Peter Schmieder for
guidance with the NMR experiments, and their helpful suggestions. We
also thank Laura Wilson from Lotus Separations for assistance with the
chiral SFC. Anastasia Hager gratefully acknowledges the Deutsche
Forschungsgemeinschaft (DFG) for her postdoctoral fellowship. D.F.
received funding from the NIH (DP2 CA186753), the Sidney Kimmel
Foundation, the Rita Allen Foundation, and Princeton University.
NR 63
TC 2
Z9 2
U1 4
U2 4
PU WILEY-V C H VERLAG GMBH
PI WEINHEIM
PA POSTFACH 101161, 69451 WEINHEIM, GERMANY
SN 0947-6539
EI 1521-3765
J9 CHEM-EUR J
JI Chem.-Eur. J.
PD AUG 22
PY 2016
VL 22
IS 35
BP 12406
EP 12414
DI 10.1002/chem.201601754
PG 9
WC Chemistry, Multidisciplinary
SC Chemistry
GA DV4DX
UT WOS:000382876500026
PM 27460418
ER
PT J
AU Maul, RW
MacCarthy, T
Frank, EG
Donigan, KA
McLenigan, MP
Yang, W
Saribasak, H
Huston, DE
Lange, SS
Woodgate, R
Gearhart, PJ
AF Maul, Robert W.
MacCarthy, Thomas
Frank, Ekaterina G.
Donigan, Katherine A.
McLenigan, Mary P.
Yang, William
Saribasak, Huseyin
Huston, Donald E.
Lange, Sabine S.
Woodgate, Roger
Gearhart, Patricia J.
TI DNA polymerase iota functions in the generation of tandem mutations
during somatic hypermutation of antibody genes
SO JOURNAL OF EXPERIMENTAL MEDICINE
LA English
DT Article
ID CLASS-SWITCH RECOMBINATION; IMMUNOGLOBULIN GENES; DEFICIENT MICE; ZETA;
ETA; MOUSE; CELLS; EXPRESSION; PROTEINS; FIDELITY
AB DNA polymerase iota (Pol iota) is an attractive candidate for somatic hypermutation in antibody genes because of its low fidelity. To identify a role for Pol iota, we analyzed mutations in two strains of mice with deficiencies in the enzyme: 129 mice with negligible expression of truncated Pol iota, and knock-in mice that express full-length Pol iota that is catalytically inactive. Both strains had normal frequencies and spectra of mutations in the variable region, indicating that loss of Pol iota did not change overall mutagenesis. We next examined if Pol iota affected tandem mutations generated by another error-prone polymerase, Pol zeta. The frequency of contiguous mutations was analyzed using a novel computational model to determine if they occur during a single DNA transaction or during two independent events. Analyses of 2,000 mutations from both strains indicated that Pol iota-compromised mice lost the tandem signature, whereas C57BL/6 mice accumulated significant amounts of double mutations. The results support a model where Pol iota occasionally accesses the replication fork to generate a first mutation, and Pol zeta extends the mismatch with a second mutation.
C1 [Maul, Robert W.; Yang, William; Saribasak, Huseyin; Gearhart, Patricia J.] NIA, Lab Mol Biol & Immunol, NIH, Baltimore, MD 21224 USA.
[MacCarthy, Thomas] SUNY Stony Brook, Dept Appl Math & Stat, Stony Brook, NY 11794 USA.
[Frank, Ekaterina G.; Donigan, Katherine A.; McLenigan, Mary P.; Huston, Donald E.; Woodgate, Roger] NICHHD, Lab Genom Integr, NIH, Rockville, MD 20850 USA.
[Lange, Sabine S.] Univ Texas MD Anderson Canc Ctr, Dept Mol Carcinogenesis, Sci Pk, Smithville, TX 78957 USA.
RP Gearhart, PJ (reprint author), NIA, Lab Mol Biol & Immunol, NIH, Baltimore, MD 21224 USA.
EM gearhartp@mail.nih.gov
FU National Institutes of Health (NIH) [GM111741]; Intramural Research
Programs of the National Institute of Child Health and Human
Development; National Institute on Aging
FX This work was supported in part by National Institutes of Health (NIH)
grant GM111741 to T. MacCarthy, and the Intramural Research Programs of
the National Institute of Child Health and Human Development to R.
Woodgate, and National Institute on Aging to P.J. Gearhart.
NR 36
TC 3
Z9 3
U1 5
U2 5
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 AUG 22
PY 2016
VL 213
IS 9
BP 1675
EP 1683
DI 10.1084/jem.20151227
PG 9
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA DU9FE
UT WOS:000382520900004
PM 27455952
ER
PT J
AU Liu, Y
Betts, MJ
Lei, J
Wei, GC
Bao, QY
Kehl, T
Russell, RB
Lochelt, M
AF Liu, Yang
Betts, Matthew J.
Lei, Janet
Wei, Guochao
Bao, Qiuying
Kehl, Timo
Russell, Robert B.
Loechelt, Martin
TI Mutagenesis of N-terminal residues of feline foamy virus Gag reveals
entirely distinct functions during capsid formation, particle assembly,
Gag processing and budding
SO RETROVIROLOGY
LA English
DT Article
DE Foamy virus; Feline foamy virus; Gag; Mutagenesis; Capsid formation;
Assembly; Genome packaging; Particle budding and maturation;
Transmission
ID ENV LEADER PROTEIN; TARGETING-RETENTION SIGNAL; PERICENTRIOLAR REGION;
VIRAL INFECTIVITY; POL POLYPROTEIN; RETROVIRAL GAG; HUMAN-CELLS;
C-TERMINUS; DOMAIN; IDENTIFICATION
AB Background: Foamy viruses (FVs) of the Spumaretrovirinae subfamily are distinct retroviruses, with many features of their molecular biology and replication strategy clearly different from those of the Orthoretroviruses, such as human immunodeficiency, murine leukemia, and human T cell lymphotropic viruses. The FV Gag N-terminal region is responsible for capsid formation and particle budding via interaction with Env. However, the critical residues or motifs in this region and their functional interaction are currently ill-defined, especially in non-primate FVs.
Results: Mutagenesis of N-terminal Gag residues of feline FV (FFV) reveals key residues essential for either capsid assembly and/or viral budding via interaction with the FFV Env leader protein (Elp). In an in vitro Gag-Elp interaction screen, Gag mutations abolishing particle assembly also interfered with Elp binding, indicating that Gag assembly is a prerequisite for this highly specific interaction. Gradient sedimentation analyses of cytosolic proteins indicate that wild-type Gag is mostly assembled into virus capsids. Moreover, proteolytic processing of Gag correlates with capsid assembly and is mostly, if not completely, independent from particle budding. In addition, Gag processing correlates with the presence of packaging-competent FFV genomic RNA suggesting that Pol encapsidation via genomic RNA is a prerequisite for Gag processing. Though an appended heterogeneous myristoylation signal rescues Gag particle budding of mutants unable to form capsids or defective in interacting with Elp, it fails to generate infectious particles that co-package Pol, as evidenced by a lack of Gag processing.
Conclusions: Changes in proteolytic Gag processing, intracellular capsid assembly, particle budding and infectivity of defined N-terminal Gag mutants highlight their essential, distinct and only partially overlapping roles during viral assembly and budding. Discussion of these findings will be based on a recent model developed for Gag-Elp interactions in prototype FV.
C1 [Liu, Yang; Lei, Janet; Wei, Guochao; Bao, Qiuying; Kehl, Timo; Loechelt, Martin] German Canc Res Ctr, Dept Mol Diagnost Oncogen Infect, Res Program Infect & Canc, Neuenheimer Feld 242, D-69120 Heidelberg, Germany.
[Betts, Matthew J.; Russell, Robert B.] Heidelberg Univ, CellNetworks, Bioquant, Neuenheimer Feld 267, D-69120 Heidelberg, Germany.
[Russell, Robert B.] BZH, Neuenheimer Feld 328, D-69120 Heidelberg, Germany.
[Liu, Yang] NCI, Ctr Canc Res, Frederick, MD 21701 USA.
[Lei, Janet] Univ Oxford, Dept Oncol, Oxford, England.
[Bao, Qiuying] East China Normal Univ, Dept Biol, Shanghai, Peoples R China.
RP Lochelt, M (reprint author), German Canc Res Ctr, Dept Mol Diagnost Oncogen Infect, Res Program Infect & Canc, Neuenheimer Feld 242, D-69120 Heidelberg, Germany.
EM m.loechelt@dkfz.de
FU German Cancer Research Center, Heidelberg, Germany; Chinese Scholarship
Council; Helmholtz International Graduate School for Cancer Research
FX This work was funded in part by the German Cancer Research Center,
Heidelberg, Germany. YL, GW, and QB are supported by PhD stipends from
the Chinese Scholarship Council. JL is supported by a PhD stipend from
the Helmholtz International Graduate School for Cancer Research. The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 57
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 1742-4690
J9 RETROVIROLOGY
JI Retrovirology
PD AUG 22
PY 2016
VL 13
AR 57
DI 10.1186/s12977-016-0291-8
PG 20
WC Virology
SC Virology
GA DT8OR
UT WOS:000381751000001
PM 27549192
ER
PT J
AU Thokala, R
Olivares, S
Mi, TJ
Maiti, S
Deniger, D
Huls, H
Torikai, H
Singh, H
Champlin, RE
Laskowski, T
McNamara, G
Cooper, LJN
AF Thokala, Radhika
Olivares, Simon
Mi, Tiejuan
Maiti, Sourindra
Deniger, Drew
Huls, Helen
Torikai, Hiroki
Singh, Harjeet
Champlin, Richard E.
Laskowski, Tamara
McNamara, George
Cooper, Laurence J. N.
TI Redirecting Specificity of T cells Using the Sleeping Beauty System to
Express Chimeric Antigen Receptors by Mix-and-Matching of V-L and V-H
Domains Targeting CD123(+) Tumors
SO PLOS ONE
LA English
DT Article
ID ACUTE MYELOID-LEUKEMIA; TOXIN-INTERLEUKIN-3 FUSION PROTEIN; ACUTE
MYELOGENOUS LEUKEMIA; ADOPTIVE IMMUNOTHERAPY; INTERLEUKIN-3 RECEPTOR;
CD28 COSTIMULATION; PHASE-I; VENOOCCLUSIVE DISEASE; CYTOTOXIC
LYMPHOCYTES; ANTITUMOR EFFICACY
AB Adoptive immunotherapy infusing T cells with engineered specificity for CD19 expressed on B-cell malignancies is generating enthusiasm to extend this approach to other hematological malignancies, such as acute myelogenous leukemia (AML). CD123, or interleukin 3 receptor alpha, is overexpressed on most AML and some lymphoid malignancies, such as acute lymphocytic leukemia (ALL), and has been an effective target for T cells expressing chimeric antigen receptors (CARs). The prototypical CAR encodes a V-H and V-L from one monoclonal antibody (mAb), coupled to a transmembrane domain and one or more cytoplasmic signaling domains. Previous studies showed that treatment of an experimental AML model with CD123-specific CAR T cells was therapeutic, but at the cost of impaired myelopoiesis, highlighting the need for systems to define the antigen threshold for CAR recognition. Here, we show that CARs can be engineered using V-H and V-L chains derived from different CD123-specific mAbs to generate a panel of CAR(+) T cells. While all CARs exhibited specificity to CD123, one V-H and V-L combination had reduced lysis of normal hematopoietic stem cells. This CAR's in vivo anti-tumor activity was similar whether signaling occurred via chimeric CD28 or CD137, prolonging survival in both AML and ALL models. Co-expression of inducible caspase 9 eliminated CAR(+) T cells. These data help support the use of CD123-specific CARs for treatment of CD123(+) hematologic malignancies.
C1 [Thokala, Radhika; Olivares, Simon; Mi, Tiejuan; Maiti, Sourindra; Deniger, Drew; Torikai, Hiroki; Singh, Harjeet; Laskowski, Tamara; McNamara, George; Cooper, Laurence J. N.] Univ Texas MD Anderson Canc Ctr, Div Pediat, Houston, TX 77030 USA.
[Thokala, Radhika] Univ Texas Houston, Grad Sch Biomed Sci, Houston, TX USA.
[Champlin, Richard E.] Univ Texas MD Anderson Canc Ctr, Stem Cell Transplantat & Cellular Therapy, Houston, TX 77030 USA.
[Cooper, Laurence J. N.] Ziopharm Oncol Inc, Boston, MA 02129 USA.
[Huls, Helen] Intrexon Corp, Germantown, MD USA.
[Deniger, Drew] NCI, Surg Branch, Ctr Canc Res, NIH, Bldg 10, Bethesda, MD 20892 USA.
RP Cooper, LJN (reprint author), Univ Texas MD Anderson Canc Ctr, Div Pediat, Houston, TX 77030 USA.; Cooper, LJN (reprint author), Ziopharm Oncol Inc, Boston, MA 02129 USA.
EM ljncooper@ziopharm.com
FU Cancer Center Core Grant [CA16672]; SPORES [CA100632, CA136411,
CA00632]; Albert J Ward Foundation; Alex's Lemonade Stand Foundation;
Burroughs Wellcome Fund; Cancer Prevention and Research Institute of
Texas; Charles B. Goddard Foundation of Texas; CLL Global Research
Foundation; Energy Transfer Partners; Estate of Noelan L. Bibler;
Gillson Longenbaugh Foundation; Harry T. Mangurian, Jr., Fund for
Leukemia Immunotherapy; Khalifa Bin Zayed Al Nahyan Foundation; Kleberg
Foundation; Leukemia and Lymphoma Society; Lymphoma Research Foundation;
Miller Foundation; National Foundation for Cancer Research; Pediatric
Cancer Research Foundation; Sheikh Khalifa Bin Zayed Al Nahyan Institute
for Personalized Cancer Therapy; University of Texas MD Anderson Cancer
Center Sister Institution Network Fund; University of Texas MD Anderson
Cancer Center Moon Shot Fund; William Lawrence and Blanche Hughes
Children's Foundation; [CA124782]; [CA120956]; [CA141303];
[CA148600]
FX This work was supported by: Cancer Center Core Grant (CA16672); RO1
(CA124782, CA120956, CA141303; CA141303); P01 (CA148600); SPORES
(CA100632, CA136411, CA00632); Albert J Ward Foundation; Alex's Lemonade
Stand Foundation; Burroughs Wellcome Fund; Cancer Prevention and
Research Institute of Texas; Charles B. Goddard Foundation of Texas; CLL
Global Research Foundation; Energy Transfer Partners; Estate of Noelan
L. Bibler; Gillson Longenbaugh Foundation; Harry T. Mangurian, Jr., Fund
for Leukemia Immunotherapy; Khalifa Bin Zayed Al Nahyan Foundation;
Kleberg Foundation; Leukemia and Lymphoma Society; Lymphoma Research
Foundation; Miller Foundation; Mr. Herb Simons; Mr. and Mrs. Joe H.
Scales; Mr. Thomas Scott; National Foundation for Cancer Research;
Pediatric Cancer Research Foundation; Sheikh Khalifa Bin Zayed Al Nahyan
Institute for Personalized Cancer Therapy; University of Texas MD
Anderson Cancer Center Sister Institution Network Fund and Moon Shot
Fund; William Lawrence and Blanche Hughes Children's Foundation. Dr.
Cooper receives a salary as CEO of Ziopharm. The specific roles of the
authors are articulated in the 'author contributions' section. The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 70
TC 3
Z9 3
U1 2
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 AUG 22
PY 2016
VL 11
IS 8
AR e0159477
DI 10.1371/journal.pone.0159477
PG 23
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DT8TP
UT WOS:000381768400006
PM 27548616
ER
PT J
AU Tong, X
Srivatsan, A
Jacobson, O
Wang, Y
Wang, ZT
Yang, XY
Niu, G
Kiesewetter, DO
Zheng, HR
Chen, XY
AF Tong, Xiao
Srivatsan, Avinash
Jacobson, Orit
Wang, Yu
Wang, Zhantong
Yang, Xiangyu
Niu, Gang
Kiesewetter, Dale O.
Zheng, Hairong
Chen, Xiaoyuan
TI Monitoring Tumor Hypoxia Using F-18-FMISO PET and Pharmacokinetics
Modeling after Photodynamic Therapy
SO SCIENTIFIC REPORTS
LA English
DT Article
ID IN-VITRO; F-18 FLUOROMISONIDAZOLE; F-18-FLUOROMISONIDAZOLE PET;
NECK-CANCER; MICROENVIRONMENT; RESPONSIVENESS; VASCULATURE; DETERMINES;
HEAD; PDT
AB Photodynamic therapy (PDT) is an efficacious treatment for some types of cancers. However, PDT-induced tumor hypoxia as a result of oxygen consumption and vascular damage can reduce the efficacy of this therapy. Measuring and monitoring intrinsic and PDT-induced tumor hypoxia in vivo during PDT is of high interest for prognostic and treatment evaluation. In the present study, static and dynamic F-18-FMISO PET were performed with mice bearing either U87MG or MDA-MB-435 tumor xenografts immediately before and after PDT at different time points. Significant difference in tumor hypoxia in response to PDT over time was found between the U87MG and MDA-MB-435 tumors in both static and dynamic PET. Dynamic PET with pharmacokinetics modeling further monitored the kinetics of F-18-FMISO retention to hypoxic sites after treatment. The K-i and k(3) parametric analysis provided information on tumor hypoxia by distinction of the specific tracer retention in hypoxic sites from its non-specific distribution in tumor. Dynamic F-18-FMISO PET with pharmacokinetics modeling, complementary to static PET analysis, provides a potential imaging tool for more detailed and more accurate quantification of tumor hypoxia during PDT.
C1 [Tong, Xiao; Srivatsan, Avinash; Jacobson, Orit; Wang, Yu; Wang, Zhantong; Yang, Xiangyu; Niu, Gang; Kiesewetter, Dale O.; Chen, Xiaoyuan] Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD 20892 USA.
[Tong, Xiao; Zheng, Hairong] Chinese Acad Sci, Shenzhen Inst Adv Technol, Paul C Lauterbur Res Ctr Biomed Imaging, Inst Biomed & Hlth Engn, Shenzhen 518055, Peoples R China.
RP Chen, XY (reprint author), Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD 20892 USA.; Zheng, HR (reprint author), Chinese Acad Sci, Shenzhen Inst Adv Technol, Paul C Lauterbur Res Ctr Biomed Imaging, Inst Biomed & Hlth Engn, Shenzhen 518055, Peoples R China.
EM hr.zheng@siat.ac.cn; shawn.chen@nih.gov
FU Intramural Research Program of the National Institute of Biomedical
Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH);
National High Technology Research and Development Program of China
[2014AA020503]
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 National High Technology
Research and Development Program of China (2014AA020503).
NR 38
TC 0
Z9 0
U1 13
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 AUG 22
PY 2016
VL 6
AR 31551
DI 10.1038/srep31551
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DT7WZ
UT WOS:000381700300001
PM 27546160
ER
PT J
AU Zheng, G
Zhang, W
Xu, JF
Yuan, A
Li, QZ
Gastwirth, JL
AF Zheng, Gang
Zhang, Wei
Xu, Jinfeng
Yuan, Ao
Li, Qizhai
Gastwirth, Joseph L.
TI Genetic risks and genetic model specification
SO JOURNAL OF THEORETICAL BIOLOGY
LA English
DT Article
DE Case-control design; Genetic model; Genetic risk; Hardy-Weinberg
equilibrium
ID CASE-CONTROL ASSOCIATION; HARDY-WEINBERG DISEQUILIBRIUM; SAMPLE-SIZE;
TREND TESTS; POWER; APPROXIMATIONS; SELECTION; GENOTYPES; MARKERS; MAX
AB Genetic risks and genetic models are often used in design and analysis of genetic epidemiology studies. A genetic model is defined in terms of two genetic risk measures: genotype relative risk and odds ratio. The impacts of choosing a risk measure on the resulting genetic models are studied in the power to detect association and deviation from Hardy Weinberg equilibrium in cases using genetic relative risk. Extensive simulations demonstrate that the power of a study to detect associations using odds ratio is lower than that using relative risk with the same value when other parameters are fixed. When the Hardy Weinberg equilibrium holds in the general population, the genetic model can be inferred by the deviation from Hardy Weinberg equilibrium in only cases. Furthermore, it is more efficient than that based on the deviation from Hardy-Weinberg equilibrium in all cases and controls. (C) 2016 Elsevier Ltd. All rights reserved.
C1 [Zheng, Gang] NHLBI, Bldg 10, Bethesda, MD 20892 USA.
[Zhang, Wei; Li, Qizhai] Chinese Acad Sci, Acad Math & Syst Sci, Key Lab Syst & Control, Beijing, Peoples R China.
[Xu, Jinfeng] Univ Hong Kong, Hong Kong, Hong Kong, Peoples R China.
[Yuan, Ao] Georgetown Univ, Washington, DC 20057 USA.
[Gastwirth, Joseph L.] George Washington Univ, Washington, DC USA.
RP Yuan, A (reprint author), Georgetown Univ, Washington, DC 20057 USA.
EM yuanao@hotmail.com
FU National Science Foundation of China [11371353, 61134013]; Chinese
Academy of Sciences [XDB13040600]
FX We would like to thank three anonymous reviewers for their careful
reading and thoughtful comments, which greatly improved our manuscript.
The authors would like to thank Ryo Yamada for some helpful discussions.
Q. Li was supported in part by the National Science Foundation of China,
(Grant nos. 11371353 and 61134013) and the Breakthrough Project of
Strategic Priority Program of the Chinese Academy of Sciences, Grant no.
XDB13040600.
NR 19
TC 1
Z9 1
U1 5
U2 8
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0022-5193
EI 1095-8541
J9 J THEOR BIOL
JI J. Theor. Biol.
PD AUG 21
PY 2016
VL 403
BP 68
EP 74
DI 10.1016/j.jtbi.2016.05.016
PG 7
WC Biology; Mathematical & Computational Biology
SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational
Biology
GA DQ1UY
UT WOS:000378987100008
PM 27181372
ER
PT J
AU Lazarus, HM
Pavletic, SZ
AF Lazarus, Hillard M.
Pavletic, Steven Z.
TI Umbilical Cord Blood-Derived Mesenchymal Stromal Cells for Reducing
Chronic Graft-Versus-Host Disease After Haploidentical Transplantation:
Just Another Labor-Intensive Strategy, or Showing the Way?
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Editorial Material
ID HEMATOLOGIC MALIGNANCY PATIENTS; ACUTE MYELOID-LEUKEMIA;
NATURAL-KILLER-CELLS; STEM-CELLS; COTRANSPLANTATION
C1 [Lazarus, Hillard M.] Case Western Reserve Univ, Cleveland, OH 44106 USA.
[Pavletic, Steven Z.] Natl Inst Hlth, Bethesda, MD USA.
RP Lazarus, HM (reprint author), Case Western Reserve Univ, Cleveland, OH 44106 USA.
NR 18
TC 0
Z9 1
U1 2
U2 2
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 AUG 20
PY 2016
VL 34
IS 24
BP 2812
EP +
DI 10.1200/JCO.2016.67.7344
PG 4
WC Oncology
SC Oncology
GA DU8MZ
UT WOS:000382469100003
PM 27400943
ER
PT J
AU Lengacher, CA
Reich, RR
Paterson, CL
Ramesar, S
Park, JY
Alinat, C
Johnson-Mallard, V
Moscoso, M
Budhrani-Shani, P
Miladinovic, B
Jacobsen, PB
Cox, CE
Goodman, M
Kip, KE
AF Lengacher, Cecile A.
Reich, Richard R.
Paterson, Carly L.
Ramesar, Sophia
Park, Jong Y.
Alinat, Carissa
Johnson-Mallard, Versie
Moscoso, Manolete
Budhrani-Shani, Pinky
Miladinovic, Branko
Jacobsen, Paul B.
Cox, Charles E.
Goodman, Matthew
Kip, Kevin E.
TI Examination of Broad Symptom Improvement Resulting From
Mindfulness-Based Stress Reduction in Breast Cancer Survivors: A
Randomized Controlled Trial
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID QUALITY-OF-LIFE; OLDER WOMEN; LONG-TERM; FOLLOW-UP; MEDITATION;
RECURRENCE; FATIGUE; SLEEP; PREVALENCE; THERAPY
AB Purpose
The purpose of this randomized trial was to evaluate the efficacy of the Mindfulness-Based Stress Reduction for Breast Cancer (MBSR[BC]) program in improving psychological and physical symptoms and quality of life among breast cancer survivors (BCSs) who completed treatment. Outcomes were assessed immediately after 6 weeks of MBSR(BC) training and 6 weeks later to test efficacy over an extended timeframe.
Patients and Methods
A total of 322 BCSs were randomly assigned to either a 6-week MBSR(BC) program (n = 155) or a usual care group (n = 167). Psychological (depression, anxiety, stress, and fear of recurrence) and physical symptoms (fatigue and pain) and quality of life (as related to health) were assessed at baseline and at 6 and 12 weeks. Linear mixed models were used to assess MBSR(BC) effects over time, and participant characteristics at baseline were also tested as moderators of MBSR(BC) effects.
Results
Results demonstrated extended improvement for the MBSR(BC) group compared with usual care in both psychological symptoms of anxiety, fear of recurrence overall, and fear of recurrence problems and physical symptoms of fatigue severity and fatigue interference (P < .01). Overall effect sizes were largest for fear of recurrence problems (d = 0.35) and fatigue severity (d = 0.27). Moderation effects showed BCSs with the highest levels of stress at baseline experienced the greatest benefit from MBSR(BC).
Conclusion
The MBSR(BC) program significantly improved a broad range of symptoms among BCSs up to 6 weeks after MBSR(BC) training, with generally small to moderate overall effect sizes.
C1 [Lengacher, Cecile A.; Ramesar, Sophia; Alinat, Carissa; Moscoso, Manolete; Kip, Kevin E.] Univ S Florida, Coll Nursing, MDC 22,12901 Bruce B Downs Blvd, Tampa, FL 33620 USA.
[Park, Jong Y.; Jacobsen, Paul B.] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA.
[Miladinovic, Branko; Cox, Charles E.] Univ S Florida, Morsani Coll Med, Tampa, FL USA.
[Reich, Richard R.] Univ S Florida, Sarasota, FL USA.
[Johnson-Mallard, Versie] Univ Florida, Coll Nursing, Gainesville, FL 32611 USA.
[Paterson, Carly L.] NCI, Rockville, MD USA.
[Budhrani-Shani, Pinky] Texas Womans Univ, Nelda C Stark Coll Nursing, Houston, TX USA.
[Goodman, Matthew] Univ Virginia, Charlottesville, VA USA.
RP Lengacher, CA (reprint author), Univ S Florida, Coll Nursing, MDC 22,12901 Bruce B Downs Blvd, Tampa, FL 33620 USA.
EM clengach@health.usf.edu
FU National Cancer Institute [1R01CA131080-01A2]; Survey Methods Core
Facility at the H. Lee Moffitt Cancer Center and Research Institute
FX Supported by Award No. 1R01CA131080-01A2 from the National Cancer
Institute and in part by the Survey Methods Core Facility at the H. Lee
Moffitt Cancer Center and Research Institute.
NR 43
TC 3
Z9 3
U1 10
U2 10
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 AUG 20
PY 2016
VL 34
IS 24
BP 2827
EP +
DI 10.1200/JCO.2015.65.7874
PG 9
WC Oncology
SC Oncology
GA DU8MZ
UT WOS:000382469100006
PM 27247219
ER
PT J
AU Wentzensen, N
Poole, EM
Trabert, B
White, E
Arslan, AA
Patel, AV
Setiawan, VW
Visvanathan, K
Weiderpass, E
Adami, HO
Black, A
Bernstein, L
Brinton, LA
Buring, J
Butler, LM
Chamosa, S
Clendenen, TV
Dossus, L
Fortner, R
Gapstur, SM
Gaudet, MM
Gram, IT
Hartge, P
Hoffman-Bolton, J
Idahl, A
Jones, M
Kaaks, R
Kirsh, V
Koh, WP
Lacey, JV
Lee, IM
Lundin, E
Merritt, MA
Onland-Moret, NC
Peters, U
Poynter, JN
Rinaldi, S
Robien, K
Rohan, T
Sandler, DP
Schairer, C
Schouten, LJ
Sjoholm, LK
Sieri, S
Swerdlow, A
Tjonneland, A
Travis, R
Trichopoulou, A
van den Brandt, PA
Wilkens, L
Wolk, A
Yang, HP
Zeleniuch-Jacquotte, A
Tworoger, SS
AF Wentzensen, Nicolas
Poole, Elizabeth M.
Trabert, Britton
White, Emily
Arslan, Alan A.
Patel, Alpa V.
Setiawan, V. Wendy
Visvanathan, Kala
Weiderpass, Elisabete
Adami, Hans-Olov
Black, Amanda
Bernstein, Leslie
Brinton, Louise A.
Buring, Julie
Butler, Lesley M.
Chamosa, Saioa
Clendenen, Tess V.
Dossus, Laure
Fortner, Renee
Gapstur, Susan M.
Gaudet, Mia M.
Gram, Inger T.
Hartge, Patricia
Hoffman-Bolton, Judith
Idahl, Annika
Jones, Michael
Kaaks, Rudolf
Kirsh, Victoria
Koh, Woon-Puay
Lacey, James V., Jr.
Lee, I-Min
Lundin, Eva
Merritt, Melissa A.
Onland-Moret, N. Charlotte
Peters, Ulrike
Poynter, Jenny N.
Rinaldi, Sabina
Robien, Kim
Rohan, Thomas
Sandler, Dale P.
Schairer, Catherine
Schouten, Leo J.
Sjoholm, Louise K.
Sieri, Sabina
Swerdlow, Anthony
Tjonneland, Anna
Travis, Ruth
Trichopoulou, Antonia
van den Brandt, Piet A.
Wilkens, Lynne
Wolk, Alicja
Yang, Hannah P.
Zeleniuch-Jacquotte, Anne
Tworoger, Shelley S.
TI Ovarian Cancer Risk Factors by Histologic Subtype: An Analysis From the
Ovarian Cancer Cohort Consortium
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID INDIVIDUAL PARTICIPANT METAANALYSIS; RANDOMIZED CONTROLLED-TRIAL;
ASSOCIATION CONSORTIUM; POOLED ANALYSIS; WOMEN; PATHOGENESIS;
INFLAMMATION; MORTALITY; PROSTATE; SMOKING
AB Purpose
An understanding of the etiologic heterogeneity of ovarian cancer is important for improving prevention, early detection, and therapeutic approaches. We evaluated 14 hormonal, reproductive, and lifestyle factors by histologic subtype in the Ovarian Cancer Cohort Consortium (OC3).
Patients and Methods
Among 1.3 million women from 21 studies, 5,584 invasive epithelial ovarian cancers were identified (3,378 serous, 606 endometrioid, 331 mucinous, 269 clear cell, 1,000 other). By using competing risks Cox proportional hazards regression stratified by study and birth year and adjusted for age, parity, and oral contraceptive use, we assessed associations for all invasive cancers by histology. Heterogeneity was evaluated by likelihood ratio test.
Results
Most risk factors exhibited significant heterogeneity by histology. Higher parity was most strongly associated with endometrioid (relative risk [RR] per birth, 0.78; 95% CI, 0.74 to 0.83) and clear cell (RR, 0.68; 95% CI, 0.61 to 0.76) carcinomas (P value for heterogeneity [P-het] < .001). Similarly, age at menopause, endometriosis, and tubal ligation were only associated with endometrioid and clear cell tumors (P-het <= .01). Family history of breast cancer (P-het = .008) had modest heterogeneity. Smoking was associated with an increased risk of mucinous (RR per 20 pack-years, 1.26; 95% CI, 1.08 to 1.46) but a decreased risk of clear cell (RR, 0.72; 95% CI, 0.55 to 0.94) tumors (P-het = .004). Unsupervised clustering by risk factors separated endometrioid, clear cell, and low-grade serous carcinomas from high-grade serous and mucinous carcinomas.
Conclusion
The heterogeneous associations of risk factors with ovarian cancer subtypes emphasize the importance of conducting etiologic studies by ovarian cancer subtypes. Most established risk factors were more strongly associated with nonserous carcinomas, which demonstrate challenges for risk prediction of serous cancers, the most fatal subtype. (C) 2016 by American Society of Clinical Oncology
C1 [Wentzensen, Nicolas; Poole, Elizabeth M.; Trabert, Britton; Black, Amanda; Brinton, Louise A.; Hartge, Patricia; Schairer, Catherine; Yang, Hannah P.] NCI, Bethesda, MD 20892 USA.
[Sandler, Dale P.] NIEHS, Bethesda, MD USA.
[Poole, Elizabeth M.; Buring, Julie; Lee, I-Min; Tworoger, Shelley S.] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Poole, Elizabeth M.; Adami, Hans-Olov; Buring, Julie; Lee, I-Min; Tworoger, Shelley S.] Harvard Univ, Boston, MA 02115 USA.
[White, Emily; Peters, Ulrike] Fred Hutchinson Canc Res Ctr, 1124 Columbia St, Seattle, WA 98104 USA.
[Arslan, Alan A.; Clendenen, Tess V.; Zeleniuch-Jacquotte, Anne] NYU, Sch Med, New York, NY 10003 USA.
[Rohan, Thomas] Albert Einstein Coll Med, New York, NY USA.
[Patel, Alpa V.; Gapstur, Susan M.; Gaudet, Mia M.] Amer Canc Soc, Atlanta, GA 30329 USA.
[Setiawan, V. Wendy] Univ Southern Calif, Los Angeles, CA USA.
[Bernstein, Leslie; Lacey, James V., Jr.] City Hope Natl Med Ctr, Duarte, CA USA.
[Visvanathan, Kala; Hoffman-Bolton, Judith] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA.
[Weiderpass, Elisabete; Gram, Inger T.] Univ Tromso Arctic Univ Norway, Tromso, Norway.
[Weiderpass, Elisabete] Canc Registry Norway, Oslo, Norway.
[Weiderpass, Elisabete; Adami, Hans-Olov; Sjoholm, Louise K.; Wolk, Alicja] Karolinska Inst, Stockholm, Sweden.
[Idahl, Annika; Lundin, Eva] Umea Univ, Umea, Sweden.
[Weiderpass, Elisabete] Folkhalsan Res Ctr, Helsinki, Finland.
[Butler, Lesley M.] Univ Pittsburgh, Pittsburgh, PA USA.
[Chamosa, Saioa] BioDonostia Res Inst, San Sebastian, Spain.
[Dossus, Laure] French Inst Hlth & Med Res, Paris, France.
[Rinaldi, Sabina] Int Agcy Res Canc, Lyon, France.
[Fortner, Renee; Kaaks, Rudolf] German Canc Res Ctr, Heidelberg, Germany.
[Jones, Michael; Swerdlow, Anthony] Inst Canc Res, Sutton, Surrey, England.
[Merritt, Melissa A.] Imperial Coll London, London, England.
[Travis, Ruth] Univ Oxford, Oxford, England.
[Kirsh, Victoria] Univ Toronto, Toronto, ON, Canada.
[Koh, Woon-Puay] Duke Univ, Singapore, Singapore.
[Onland-Moret, N. Charlotte] Univ Med Ctr Utrecht, Utrecht, Netherlands.
[Schouten, Leo J.; van den Brandt, Piet A.] Maastricht Univ, Maastricht, Netherlands.
[Poynter, Jenny N.] Univ Minnesota, Minneapolis, MN USA.
[Robien, Kim] George Washington Univ, Washington, DC USA.
[Sieri, Sabina] Natl Canc Inst, Rome, Italy.
[Tjonneland, Anna] Danish Canc Soc, Copenhagen, Denmark.
[Trichopoulou, Antonia] Hellenic Hlth Fdn, Athens, Greece.
[Wilkens, Lynne] Univ Hawaii, Ctr Canc, Honolulu, HI 96822 USA.
RP Wentzensen, N (reprint author), NCI, Div Canc Epidemiol & Genet, Room 7-E114,9609 Med Ctr Dr, Bethesda, MD 20892 USA.
EM wentzenn@mail.nih.gov
RI Weiderpass, Elisabete/M-4029-2016; Trabert, Britton/F-8051-2015;
Onland-Moret, N. Charlotte/G-9185-2011;
OI Weiderpass, Elisabete/0000-0003-2237-0128; Fortner,
Renee/0000-0002-1426-8505; Robien, Kim/0000-0002-2120-2280; Sandler,
Dale/0000-0002-6776-0018; Zeleniuch-Jacquotte, Anne/0000-0001-9350-1303
FU Department of Defense Ovarian Cancer Research Program
[W81XWH-12-1-0561]; Breakthrough Breast Cancer; Institute of Cancer
Research; National Health Service; National Cancer Institute (NCI) [K05
CA154337]; Office of Dietary Supplements (VITAL [Vitamins and Lifestyle
study cohort]); Iowa Women's Health Study [R01 CA39742]; National
Institutes of Health/NCI grant [UM1 CA182876, CA047988, HL043851,
HL080467, HL099355, CA164973, R01 CA77398, UM1 CA169417, UM1 CA186107,
P01 CA87969, UM1 CA176726, R01 CA67262]; Swedish Cancer Society; Swedish
Research Council; Intramural Research Program of the American Cancer
Society; NCI Intramural Research Program; Intramural Research Program of
the National Institutes of Health; National Institute of Environmental
Health Sciences [Z01ES044005]; European Commission (DG-SANCO);
International Agency for Research on Cancer; Danish Cancer Society
(Denmark); Ligue Contre le Cancer (France); Institut Gustave Roussy
(France); Mutuelle Generale de l'Education Nationale (France); Institut
National de la Sante et de la Recherche Medicale (France); German Cancer
Aid (Germany); German Cancer Research Center (Germany); Federal Ministry
of Education and Research (Germany); Hellenic Health Foundation
(Greece); Associazione Italiana per la Ricerca sul Cancro-Italy;
National Research Council (Italy); Dutch Ministry of Public Health,
Welfare and Sports (the Netherlands); Netherlands Cancer Registry (the
Netherlands); LK Research Funds (the Netherlands); Dutch Prevention
Funds (the Netherlands); Dutch Zorg Onderzoek Nederland (the
Netherlands); World Cancer Research Fund (the Netherlands); Statistics
Netherlands (the Netherlands); Nordic Centre of Excellence Programme on
Food, Nutrition and Health (Norway); Health Research Fund (Spain)
[PI13/00061]; Instituto San Carlos III Las Redes Tematicas de
Investigacion Cooperativa en Salud (Spain) [RD06/0020]; regional
government of Spain (Andalucia); regional government of Spain
(Asturias); regional government of Spain (Basque Country); regional
government of Spain (Murcia) [6236]; regional government of Spain
(Navarra); Swedish Cancer Society (Sweden); Swedish Scientific Council
(Sweden); County Council of Skane (Sweden); County Council of
Vasterbotten (Sweden); Cancer Research UK (United Kingdom) [14136,
C570/A16491]; Medical Research Council (United Kingdom) [1000143]
FX Supported by Department of Defense Ovarian Cancer Research Program Grant
No. W81XWH-12-1-0561. The UK Breakthrough Generations Study is supported
by Breakthrough Breast Cancer and the Institute of Cancer Research. The
Institute for Cancer Research is supported by National Health Service
funding to the National Institute for Health Research Biomedical
Research Centre. Also supported by K05 CA154337 from the National Cancer
Institute (NCI) and Office of Dietary Supplements (VITAL [Vitamins and
Lifestyle study cohort]); R01 CA39742 (Iowa Women's Health Study);
National Institutes of Health/NCI grant UM1 CA182876 (Singapore Chinese
Health Study); CA047988, HL043851, HL080467, and HL099355 (Women's
Health Study); CA164973 (Multiethnic Cohort); R01 CA77398 and UM1
CA169417 (California Teachers Study); UM1 CA186107, P01 CA87969, UM1
CA176726, and R01 CA67262 (Nurses' Health Study, Nurses' Health Study
II); grants from the Swedish Cancer Society and Swedish Research Council
(Swedish Women's Lifestyle and Health cohort study); and the Swedish
Research Council (Swedish Mammography Cohort). All aspects of the Cancer
Prevention Study II were funded by the Intramural Research Program of
the American Cancer Society and by the NCI Intramural Research Program,
Intramural Research Program of the National Institutes of Health, and
National Institute of Environmental Health Sciences (Z01ES044005; Sister
Study). The coordination of European Prospective Investigation Into
Cancer (EPIC) is supported by the European Commission (DG-SANCO) and the
International Agency for Research on Cancer. The national cohorts are
supported by the Danish Cancer Society (Denmark); Ligue Contre le
Cancer, Institut Gustave Roussy, Mutuelle Generale de l'Education
Nationale, and Institut National de la Sante et de la Recherche Medicale
(France); German Cancer Aid, German Cancer Research Center, and Federal
Ministry of Education and Research (Germany); Hellenic Health Foundation
(Greece); Associazione Italiana per la Ricerca sul Cancro-Italy and
National Research Council (Italy); Dutch Ministry of Public Health,
Welfare and Sports, Netherlands Cancer Registry, LK Research Funds,
Dutch Prevention Funds, Dutch Zorg Onderzoek Nederland, World Cancer
Research Fund, and Statistics Netherlands (the Netherlands); Nordic
Centre of Excellence Programme on Food, Nutrition and Health (Norway);
Health Research Fund, PI13/00061 to Granada, regional governments of
Spain (Andalucia, Asturias, Basque Country, Murcia [No. 6236], and
Navarra), and Instituto San Carlos III Las Redes Tematicas de
Investigacion Cooperativa en Salud (RD06/0020; Spain); Swedish Cancer
Society, Swedish Scientific Council, and County Councils of Skane and
Vasterbotten (Sweden); and Cancer Research UK (14136 to EPIC-Norfolk,
C570/A16491 to EPIC-Oxford) and Medical Research Council (1000143 to
EPIC-Norfolk; United Kingdom).
NR 38
TC 4
Z9 4
U1 13
U2 14
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 AUG 20
PY 2016
VL 34
IS 24
BP 2888
EP +
DI 10.1200/JCO.2016.66.8178
PG 19
WC Oncology
SC Oncology
GA DU8MZ
UT WOS:000382469100014
PM 27325851
ER
PT J
AU Wu, YC
Chandris, P
Winter, PW
Kim, EY
Jaumouille, V
Kumar, A
Guo, M
Leung, JM
Smith, C
Rey-Suarez, I
Liu, HF
Waterman, CM
Ramamurthi, KS
La Riviere, PJ
Shroff, H
AF Wu, Yicong
Chandris, Panagiotis
Winter, Peter W.
Kim, Edward Y.
Jaumouille, Valentin
Kumar, Abhishek
Guo, Min
Leung, Jacqueline M.
Smith, Corey
Rey-Suarez, Ivan
Liu, Huafeng
Waterman, Clare M.
Ramamurthi, Kumaran S.
La Riviere, Patrick J.
Shroff, Hari
TI Simultaneous multiview capture and fusion improves spatial resolution in
wide-field and light-sheet microscopy
SO OPTICA
LA English
DT Article
ID PLANE ILLUMINATION MICROSCOPY; TOXOPLASMA-GONDII; BACILLUS-SUBTILIS;
FLUORESCENCE MICROSCOPY; DECONVOLUTION; LOCALIZATION; SPORULATION;
PROTEIN; 3D
AB Most fluorescence microscopes are inefficient, collecting only a small fraction of the emitted light at any instant. Besides wasting valuable signal, this inefficiency also reduces spatial resolution and causes imaging volumes to exhibit significant resolution anisotropy. We describe microscopic and computational techniques that address these problems by simultaneously capturing and subsequently fusing and deconvolving multiple specimen views. Unlike previous methods that serially capture multiple views, our approach improves spatial resolution without introducing any additional illumination dose or compromising temporal resolution relative to conventional imaging. When applying our methods to single-view wide-field or dual-view light-sheet microscopy, we achieve a twofold improvement in volumetric resolution (similar to 235 nm x 235 nm x 340 nm) as demonstrated on a variety of samples including microtubules in Toxoplasma gondii, SpoVM in sporulating Bacillus subtilis, and multiple protein distributions and organelles in eukaryotic cells. In every case, spatial resolution is improved with no drawback by harnessing previously unused fluorescence. (C) 2016 Optical Society of America
C1 [Wu, Yicong; Chandris, Panagiotis; Winter, Peter W.; Kumar, Abhishek; Guo, Min; Rey-Suarez, Ivan; Shroff, Hari] Natl Inst Biomed Imaging & Bioengn, Sect High Resolut Opt Imaging, NIH, Bethesda, MD 20892 USA.
[Kim, Edward Y.; Ramamurthi, Kumaran S.] NCI, Mol Biol Lab, NIH, Bldg 37, Bethesda, MD 20892 USA.
[Jaumouille, Valentin; Waterman, Clare M.] NHLBI, Cell Biol & Physiol Ctr, NIH, Bldg 10, Bethesda, MD 20892 USA.
[Guo, Min; Liu, Huafeng] Zhejiang Univ, State Key Lab Modern Opt Instrumentat, Coll Opt Sci & Engn, Hangzhou 310027, Peoples R China.
[Leung, Jacqueline M.] Indiana Univ, Dept Biol, Bloomington, IN 47405 USA.
[Smith, Corey; La Riviere, Patrick J.] Univ Chicago, Dept Radiol, Chicago, IL 60637 USA.
[La Riviere, Patrick J.; Shroff, Hari] Marine Biol Lab, Whitman Ctr, Woods Hole, MA 02543 USA.
RP Wu, YC (reprint author), Natl Inst Biomed Imaging & Bioengn, Sect High Resolut Opt Imaging, NIH, Bethesda, MD 20892 USA.
EM yicong.wu@nih.gov
FU National Institute of Biomedical Imaging and Bioengineering (NIBIB);
National Cancer Institute (NCI); National Heart, Lung, and Blood
Institute (NHLBI); Marine Biological Laboratory (MBL) MBL-UChicago
Exploratory Research Fund Research Award; National Institute of General
Medical Sciences (NIGMS) [R25GM109439]; National Natural Science
Foundation of China (NSFC) [61427807, 61271083, 61525106];
Colciencias-Fulbright Scholarship; March of Dimes Foundation (MODF)
[6-FY15-198]
FX National Institute of Biomedical Imaging and Bioengineering (NIBIB);
National Cancer Institute (NCI); National Heart, Lung, and Blood
Institute (NHLBI); Marine Biological Laboratory (MBL) MBL-UChicago
Exploratory Research Fund Research Award; National Institute of General
Medical Sciences (NIGMS) (R25GM109439); National Natural Science
Foundation of China (NSFC) (61427807, 61271083, 61525106);
Colciencias-Fulbright Scholarship; March of Dimes Foundation (MODF)
(6-FY15-198).
NR 40
TC 2
Z9 2
U1 17
U2 17
PU OPTICAL SOC AMER
PI WASHINGTON
PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA
SN 2334-2536
J9 OPTICA
JI Optica
PD AUG 20
PY 2016
VL 3
IS 8
BP 897
EP 910
DI 10.1364/OPTICA.3.000897
PG 14
WC Optics
SC Optics
GA DU1YU
UT WOS:000382007700019
PM 27761486
ER
PT J
AU Dacks, PA
Armstrong, JJ
Brannan, SK
Carman, AJ
Green, AM
Kirkman, MS
Krakoff, LR
Kuller, LH
Launer, LJ
Lovestone, S
Merikle, E
Neumann, PJ
Rockwood, K
Shineman, DW
Stefanacci, RG
Velentgas, P
Viswanathan, A
Whitmer, RA
Williamson, JD
Fillit, HM
AF Dacks, Penny A.
Armstrong, Joshua J.
Brannan, Stephen K.
Carman, Aaron J.
Green, Allan M.
Kirkman, M. Sue
Krakoff, Lawrence R.
Kuller, Lewis H.
Launer, Lenore J.
Lovestone, Simon
Merikle, Elizabeth
Neumann, Peter J.
Rockwood, Kenneth
Shineman, Diana W.
Stefanacci, Richard G.
Velentgas, Priscilla
Viswanathan, Anand
Whitmer, Rachel A.
Williamson, Jeff D.
Fillit, Howard M.
TI A call for comparative effectiveness research to learn whether routine
clinical care decisions can protect from dementia and cognitive decline
SO ALZHEIMERS RESEARCH & THERAPY
LA English
DT Review
DE Comparative effectiveness; Dementia; Alzheimer's; Prevention; Cognitive
decline; Cognitive aging; Comorbidity; Repurposing; Hypertension;
Diabetes
ID CALCIUM-CHANNEL BLOCKERS; ALZHEIMERS-DISEASE; ANTIHYPERTENSIVE DRUGS;
HYPERTENSIVE PATIENTS; PROSPECTIVE COHORT; BLOOD-PRESSURE;
HEART-FAILURE; OLDER-ADULTS; IMPAIRMENT; PREVENTION
AB Common diseases like diabetes, hypertension, and atrial fibrillation are probable risk factors for dementia, suggesting that their treatments may influence the risk and rate of cognitive and functional decline. Moreover, specific therapies and medications may affect long-term brain health through mechanisms that are independent of their primary indication. While surgery, benzodiazepines, and anti-cholinergic drugs may accelerate decline or even raise the risk of dementia, other medications act directly on the brain to potentially slow the pathology that underlies Alzheimer's and other dementia. In other words, the functional and cognitive decline in vulnerable patients may be influenced by the choice of treatments for other medical conditions. Despite the importance of these questions, very little research is available. The Alzheimer's Drug Discovery Foundation convened an advisory panel to discuss the existing evidence and to recommend strategies to accelerate the development of comparative effectiveness research on how choices in the clinical care of common chronic diseases may protect from cognitive decline and dementia.
C1 [Dacks, Penny A.; Carman, Aaron J.; Shineman, Diana W.; Fillit, Howard M.] Alzheimers Drug Discovery Fdn, 57 West 57th St Suite 901, New York, NY 10019 USA.
[Armstrong, Joshua J.; Rockwood, Kenneth] Dalhousie Univ, Dept Med, Geriatr Med Res Unit, Halifax, NS, Canada.
[Brannan, Stephen K.; Merikle, Elizabeth] Takeda Pharmaceut, Deerfield, IL USA.
[Green, Allan M.] Attorney Law, Cambridge, MA USA.
[Kirkman, M. Sue] Univ N Carolina, Div Endocrinol & Metab, Dept Med, Sch Med, Chapel Hill, NC USA.
[Krakoff, Lawrence R.] Icahn Sch Med Mt Sinai, New York, NY 10029 USA.
[Kuller, Lewis H.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA.
[Launer, Lenore J.] NIA, Intramural Res Program, NIH, Bethesda, MD 20892 USA.
[Lovestone, Simon] Univ Oxford, Dept Psychiat, Oxford, England.
[Neumann, Peter J.] Tufts Med Ctr, Inst Clin Res & Hlth Policy Studies, Ctr Evaluat Value & Risk Hlth, Boston, MA USA.
[Rockwood, Kenneth] DGI Clin, Halifax, NS, Canada.
[Rockwood, Kenneth] Nova Scotia Hlth Author, Halifax, NS, Canada.
[Stefanacci, Richard G.] Thomas Jefferson Coll Populat Hlth, Access Grp, Philadelphia, PA USA.
[Velentgas, Priscilla] Quintiles Real World Late Phase Res, Sci Affairs, Cambridge, MA USA.
[Viswanathan, Anand] Amer Heart Assoc, Boston, MA USA.
[Viswanathan, Anand] Harvard Med Sch, Massachusetts Gen Hosp, Ctr Stroke Res, Dept Neurol,Hemorrhag Stroke Res Program, Boston, MA USA.
[Whitmer, Rachel A.] Kaiser Permanente Div Res Populat Sci & Brain Agi, Oakland, CA USA.
[Williamson, Jeff D.] Wake Forest Univ, Sch Med, Winston Salem, NC 27109 USA.
RP Dacks, PA (reprint author), Alzheimers Drug Discovery Fdn, 57 West 57th St Suite 901, New York, NY 10019 USA.
EM pdacks@alzdiscovery.org
FU Alzheimer's Drug Discovery Foundation; Canadian Consortium on
Neurodegeneration in Aging; Intramural Research Program, National
Institute on Aging, NIH; NIH-NIA grants [K23 AG028726, R01AG047975]
FX This position paper and the corresponding advisory panel were funded by
the Alzheimer's Drug Discovery Foundation. Support for authors' time was
provided by the Canadian Consortium on Neurodegeneration in Aging (JJA);
the Intramural Research Program, National Institute on Aging, NIH (LJL);
NIH-NIA grants K23 AG028726 and R01AG047975 (AV). Takeda Pharmaceuticals
provided some support for the advisory panel; the American Heart
Association supported the cost of travel for their representative (AV).
NR 68
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 1758-9193
J9 ALZHEIMERS RES THER
JI Alzheimers Res. Ther.
PD AUG 20
PY 2016
VL 8
AR 33
DI 10.1186/s13195-016-0200-3
PG 9
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA DU9FR
UT WOS:000382522300001
PM 27543171
ER
PT J
AU Berrigan, D
Troiano, RP
Graubard, BI
AF Berrigan, David
Troiano, Richard P.
Graubard, Barry I.
TI BMI and mortality: the limits of epidemiological evidence
SO LANCET
LA English
DT Editorial Material
ID BODY-MASS INDEX; ADULTS; INTERVENTIONS; DISEASE; LIFE
C1 [Berrigan, David; Troiano, Richard P.] NCI, Div Canc Control & Populat Sci, NIH, Bethesda, MD 20892 USA.
[Graubard, Barry I.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
RP Berrigan, D (reprint author), NCI, Div Canc Control & Populat Sci, NIH, Bethesda, MD 20892 USA.
EM berrigad@mail.nih.gov
NR 15
TC 1
Z9 1
U1 2
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0140-6736
EI 1474-547X
J9 LANCET
JI Lancet
PD AUG 20
PY 2016
VL 388
IS 10046
BP 734
EP 736
DI 10.1016/S0140-6736(16)30949-7
PG 3
WC Medicine, General & Internal
SC General & Internal Medicine
GA DT6UH
UT WOS:000381619200005
PM 27423263
ER
PT J
AU Di Angelantonio, E
Bhupathiraju, SN
Wormser, D
Gao, P
Kaptoge, S
de Gonzalez, AB
Cairns, BJ
Huxley, R
Jackson, CL
Joshy, G
Lewington, S
Manson, JE
Murphy, N
Patel, AV
Samet, JM
Woodward, M
Zheng, W
Zhou, M
Bansal, N
Barricarte, A
Carter, B
Cerhan, JR
Collins, R
Smith, GD
Fang, X
Franco, OH
Green, J
Halsey, J
Hildebrand, JS
Jung, KJ
Korda, RJ
McLerran, DF
Moore, SC
O'Keeff, LM
Paige, E
Ramond, A
Reeves, GK
Rolland, B
Sacerdote, C
Sattar, N
Sofianopoulou, E
Stevens, J
Thun, M
Ueshima, H
Yang, L
Yun, YD
Willeit, P
Banks, E
Beral, V
Chen, Z
Gapstur, SM
Gunter, MJ
Hartge, P
Jee, SH
Lam, TH
Peto, R
Potter, JD
Willett, WC
Thompson, SG
Danesh, J
Hu, FB
AF Di Angelantonio, Emanuele
Bhupathiraju, Shilpa N.
Wormser, David
Gao, Pei
Kaptoge, Stephen
de Gonzalez, Amy Berrington
Cairns, Benjamin J.
Huxley, Rachel
Jackson, Chandra L.
Joshy, Grace
Lewington, Sarah
Manson, JoAnn E.
Murphy, Neil
Patel, Alpa V.
Samet, Jonathan M.
Woodward, Mark
Zheng, Wei
Zhou, Maigen
Bansal, Narinder
Barricarte, Aurelio
Carter, Brian
Cerhan, James R.
Collins, Rory
Smith, George Davey
Fang, Xianghua
Franco, Oscar H.
Green, Jane
Halsey, Jim
Hildebrand, Janet S.
Jung, Keum Ji
Korda, Rosemary J.
McLerran, Dale F.
Moore, Steven C.
O'Keeff, Linda M.
Paige, Ellie
Ramond, Anna
Reeves, Gillian K.
Rolland, Betsy
Sacerdote, Carlotta
Sattar, Naveed
Sofianopoulou, Eleni
Stevens, June
Thun, Michael
Ueshima, Hirotsugu
Yang, Ling
Yun, Young Duk
Willeit, Peter
Banks, Emily
Beral, Valerie
Chen, Zhengming
Gapstur, Susan M.
Gunter, Marc J.
Hartge, Patricia
Jee, Sun Ha
Lam, Tai-Hing
Peto, Richard
Potter, John D.
Willett, Walter C.
Thompson, Simon G.
Danesh, John
Hu, Frank B.
CA Global BMI Mortality Collaboration
TI Body-mass index and all-cause mortality: individual-participant-data
meta-analysis of 239 prospective studies in four continents
SO LANCET
LA English
DT Article
ID CARDIOVASCULAR-DISEASE; ABDOMINAL ADIPOSITY; RISK-FACTORS; OBESITY;
ASSOCIATION; POPULATION; OVERWEIGHT; METHODOLOGY; TRENDS; COHORT
AB Background Overweight and obesity are increasing worldwide. To help assess their relevance to mortality in different populations we conducted individual-participant data meta-analyses of prospective studies of body-mass index (BMI), limiting confounding and reverse causality by restricting analyses to never-smokers and excluding pre-existing disease and the first 5 years of follow-up.
Methods Of 10 625 411 participants in Asia, Australia and New Zealand, Europe, and North America from 239 prospective studies (median follow-up 13.7 years, IQR 11.4-14.7), 3 951 455 people in 189 studies were never-smokers without chronic diseases at recruitment who survived 5 years, of whom 385 879 died. The primary analyses are of these deaths, and study, age, and sex adjusted hazard ratios (HRs), relative to BMI 22.5-<25.0 kg/m(2).
Findings All-cause mortality was minimal at 20.0-25.0 kg/m(2) (HR 1.00, 95% CI 0.98-1.02 for BMI 20.0-<22.5 kg/m(2); 1.00, 0.99-1.01 for BMI 22.5-<25.0 kg/m(2)), and increased significantly both just below this range (1.13, 1.09-1.17 for BMI 18.5-<20.0 kg/m(2); 1.51, 1.43-1.59 for BMI 15.0-<18.5) and throughout the overweight range (1.07, 1.07-1.08 for BMI 25.0-<27.5 kg/m(2); 1.20, 1.18-1.22 for BMI 27.5-<30.0 kg/m(2)). The HR for obesity grade 1 (BMI 30.0-<35.0 kg/m(2)) was 1.45, 95% CI 1.41-1.48; the HR for obesity grade 2 (35.0-<40.0 kg/m(2)) was 1.94, 1.87-2.01; and the HR for obesity grade 3 (40.0-<60.0 kg/m(2)) was 2.76, 2.60-2.92. For BMI over 25.0 kg/m(2), mortality increased approximately log-linearly with BMI; the HR per 5 kg/m(2) units higher BMI was 1.39 (1.34-1.43) in Europe, 1.29 (1.26-1.32) in North America, 1.39 (1.34-1.44) in east Asia, and 1.31 (1.27-1.35) in Australia and New Zealand. This HR per 5 kg/m(2) units higher BMI (for BMI over 25 kg/m(2)) was greater in younger than older people (1.52, 95% CI 1.47-1.56, for BMI measured at 35-49 years vs 1.21, 1.17-1.25, for BMI measured at 70-89 years; p(heterogeneity) < 0.0001), greater in men than women (1.51, 1.46-1.56, vs 1.30, 1.26-1.33; p(heterogeneity) < 0.0001), but similar in studies with self-reported and measured BMI.
Interpretation The associations of both overweight and obesity with higher all-cause mortality were broadly consistent in four continents. This finding supports strategies to combat the entire spectrum of excess adiposity in many populations.
C1 [Di Angelantonio, Emanuele; Wormser, David; Gao, Pei; Kaptoge, Stephen; Bansal, Narinder; O'Keeff, Linda M.; Paige, Ellie; Ramond, Anna; Sofianopoulou, Eleni; Willeit, Peter; Thompson, Simon G.; Danesh, John] Univ Cambridge, Cambridge, England.
[Bhupathiraju, Shilpa N.] Harvard Univ, Harvard TH Chan Sch Publ Hlth, Boston, MA 02115 USA.
[Gao, Pei] Peking Univ, Beijing 100871, Peoples R China.
[de Gonzalez, Amy Berrington; Hartge, Patricia] Natl Canc Inst, Bethesda, MD USA.
[Cairns, Benjamin J.; Lewington, Sarah; Woodward, Mark; Collins, Rory; Green, Jane; Halsey, Jim; Reeves, Gillian K.; Yang, Ling; Beral, Valerie; Chen, Zhengming; Peto, Richard] Univ Oxford, S Parks Rd, Oxford, England.
[Huxley, Rachel] Curtin Univ, Perth, WA 6845, Australia.
[Jackson, Chandra L.] Harvard Univ, Sch Med, Boston, MA USA.
[Joshy, Grace] Australian Natl Univ, GPO Box 4, Canberra, ACT, Australia.
[Manson, JoAnn E.] Harvard Univ, Sch Med, Harvard TH Chan Sch Publ Hlth, Boston, MA USA.
[Murphy, Neil] Imperial Coll London, London, England.
[Patel, Alpa V.; Carter, Brian; Hildebrand, Janet S.; Thun, Michael; Gapstur, Susan M.] Amer Canc Soc, Atlanta, GA 30329 USA.
[Samet, Jonathan M.] Univ So Calif, Los Angeles, CA USA.
[Woodward, Mark] Univ Sydney, Sydney, NSW, Australia.
[Woodward, Mark] Johns Hopkins Univ, Baltimore, MD USA.
[Zheng, Wei] Vanderbilt Univ Sch Med, Nashville, TN USA.
[Zhou, Maigen] Chinese Ctr Dis Control & Prevent, Beijing, Peoples R China.
[Barricarte, Aurelio] Consortium Biomed Res Epidemiol & Publ Hlth, Navarre Publ Hlth Inst, Pamplona, Spain.
[Cerhan, James R.] Mayo Clin, Rochester, MN USA.
[Smith, George Davey] Univ Bristol, Bristol, Avon, England.
[Fang, Xianghua] Capital Med Univ, Beijing, Peoples R China.
[Franco, Oscar H.] Univ Med Ctr Rotterdam, Rotterdam, Netherlands.
[Jung, Keum Ji; Jee, Sun Ha] Yonsei Univ, Seoul 120749, South Korea.
[Korda, Rosemary J.] Australian Natl Univ, GPO Box 4, Canberra, ACT, Australia.
[McLerran, Dale F.] Fred Hutchinson Canc Res Ctr, 1124 Columbia St, Seattle, WA 98104 USA.
[Moore, Steven C.; Rolland, Betsy] Natl Canc Inst, Bethesda, MD USA.
[Sacerdote, Carlotta] Univ Turin, Ctr Canc Prevent, Turin, Italy.
[Sattar, Naveed] Univ Glasgow, Glasgow, Lanark, Scotland.
[Stevens, June] Univ N Carolina, Chapel Hill, NC USA.
[Ueshima, Hirotsugu] Shiga Univ, Med Sci, Shiga, Japan.
[Yun, Young Duk] Hlth Insurance Policy Res Inst, Seoul, South Korea.
[Willeit, Peter] Med Univ Innsbruck, A-6020 Innsbruck, Austria.
[Banks, Emily] Australian Natl Univ Canberra, Canberra, ACT, Australia.
[Gunter, Marc J.] Int Agcy Res Canc, 150 Cours Albert Thomas, F-69372 Lyon, France.
[Lam, Tai-Hing] Univ Hong Kong, Hong Kong, Peoples R China.
[Potter, John D.] Massey Univ, Wellington, New Zealand.
[Willett, Walter C.; Hu, Frank B.] Harvard Univ, Sch Med, Harvard TH Chan Sch Publ Hlth, Boston, MA USA.
RP Di Angelantonio, E (reprint author), Univ Cambridge, Cambridge, England.
RI Huxley, Rachel/C-7032-2013; Zheng, Wei/O-3351-2013; Woodward,
Mark/D-8492-2015; Moore, Steven/D-8760-2016; Jackson,
Chandra/A-6291-2017; Murphy, Neil/E-1189-2017; Ulmer, Hanno/C-3488-2011;
OI Huxley, Rachel/0000-0002-2705-6616; Zheng, Wei/0000-0003-1226-070X;
Davey Smith, George/0000-0002-1407-8314; Moore,
Steven/0000-0002-8169-1661; Jackson, Chandra/0000-0002-0915-8272;
Murphy, Neil/0000-0003-3347-8249; Ulmer, Hanno/0000-0001-5911-1002;
Ramond, Anna/0000-0002-9958-3693
FU UK Medical Research Council; British Heart Foundation; National
Institute for Health Research; US National Institutes of Health
FX UK Medical Research Council, British Heart Foundation, National
Institute for Health Research, US National Institutes of Health.
NR 43
TC 3
Z9 3
U1 11
U2 20
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0140-6736
EI 1474-547X
J9 LANCET
JI Lancet
PD AUG 20
PY 2016
VL 388
IS 10046
BP 776
EP 786
DI 10.1016/S0140-6736(16)30175-1
PG 11
WC Medicine, General & Internal
SC General & Internal Medicine
GA DT6UH
UT WOS:000381619200026
ER
PT J
AU Koonin, EV
AF Koonin, Eugene V.
TI Viruses and mobile elements as drivers of evolutionary transitions
SO PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES
LA English
DT Review
DE evolutionary transitions; mobile genetic elements; parasites; viruses;
antivirus defence; host-parasite coevolution
ID RESTRICTION-MODIFICATION SYSTEMS; TOXIN-ANTITOXIN SYSTEMS; PROGRAMMED
CELL-DEATH; CRISPR-CAS SYSTEMS; TRANSPOSABLE ELEMENTS; GENE-TRANSFER;
AGGREGATIVE MULTICELLULARITY; REVERSE-TRANSCRIPTASE; DELETERIOUS
MUTATIONS; COMPARATIVE GENOMICS
AB The history of life is punctuated by evolutionary transitions which engender emergence of new levels of biological organization that involves selection acting at increasingly complex ensembles of biological entities. Major evolutionary transitions include the origin of prokaryotic and then eukaryotic cells, multicellular organisms and eusocial animals. All or nearly all cellular life forms are hosts to diverse selfish genetic elements with various levels of autonomy including plasmids, transposons and viruses. I present evidence that, at least up to and including the origin of multicellularity, evolutionary transitions are driven by the coevolution of hosts with these genetic parasites along with sharing of 'public goods'. Selfish elements drive evolutionary transitions at two distinct levels. First, mathematical modelling of evolutionary processes, such as evolution of primitive replicator populations or unicellular organisms, indicates that only increasing organizational complexity, e.g. emergence ofmulticellular aggregates, can prevent the collapse of the host-parasite system under the pressure of parasites. Second, comparative genomic analysis reveals numerous cases of recruitment of genes with essential functions in cellular life forms, including those that enable evolutionary transitions.
This article is part of the themed issue 'The major synthetic evolutionary transitions'.
C1 [Koonin, Eugene V.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
RP Koonin, EV (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
EM koonin@ncbi.nlm.nih.gov
FU US Department of Health and Human Services
FX This research is supported by intramural funds of the US Department of
Health and Human Services (to the National Library of Medicine).
NR 189
TC 2
Z9 2
U1 20
U2 20
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 AUG 19
PY 2016
VL 371
IS 1701
AR 20150442
DI 10.1098/rstb.2015.0442
PG 13
WC Biology
SC Life Sciences & Biomedicine - Other Topics
GA DX5ZF
UT WOS:000384460600005
ER
PT J
AU Corona, A
Desantis, J
Massari, S
Distinto, S
Masaoka, T
Sabatini, S
Esposito, F
Manfroni, G
Maccioni, E
Cecchetti, V
Pannecouque, C
Le Grice, SFJ
Tramontano, E
Tabarrini, O
AF Corona, Angela
Desantis, Jenny
Massari, Serena
Distinto, Simona
Masaoka, Takashi
Sabatini, Stefano
Esposito, Francesca
Manfroni, Giuseppe
Maccioni, Elias
Cecchetti, Violetta
Pannecouque, Christophe
Le Grice, Stuart F. J.
Tramontano, Enzo
Tabarrini, Oriana
TI Studies on Cycloheptathiophene-3-carboxamide Derivatives as Allosteric
HIV-1 RibonucleaseH Inhibitors
SO CHEMMEDCHEM
LA English
DT Article; Proceedings Paper
CT 23rd National Meeting of the Medicinal-Chemistry-Division of the
Italian-Chemical-Society (DCF-SCI)
CY 2015
CL Salerno, ITALY
SP Italian Chem Soc, Med Chem Div
DE allosterism antiviral agents inhibitors medicinal chemistry
ribonucleases
ID DIKETO ACID-DERIVATIVES; RNASE-H FUNCTION; IMMUNODEFICIENCY-VIRUS
TYPE-1; REVERSE-TRANSCRIPTASE; DUAL INHIBITORS; COLORIMETRIC ASSAY;
DNA-POLYMERASE; ACTIVE-SITE; IDENTIFICATION; RESIDUES
AB Despite the significant progress achieved with combination antiretroviral therapy in the fight against human immunodeficiency virus (HIV) infection, the difficulty to eradicate the virus together with the rapid emergence of multidrug-resistant strains clearly underline a pressing need for innovative agents, possibly endowed with novel mechanisms of action. In this context, owing to its essential role in HIV genome replication, the reverse transcriptase associated ribonucleaseH (RNaseH) has proven to be an appealing target. To identify new RNaseH inhibitors, an in-house cycloheptathiophene-3-carboxamide library was screened; this led to compounds endowed with inhibitory activity, the structural optimization of which led to the catechol derivative 2-(3,4-dihydroxybenzamido)-N-(pyridin-2-yl)-5,6,7,8-tetrahydro-4H-cyclohepta[b]thiophene-3-carboxamide (compound 33) with an IC50 value on the RNaseH activity in the nanomolar range. Mechanistic studies suggested selective inhibition of the RNaseH through binding to an innovative allosteric site, which could be further exploited to enrich this class of inhibitors.
C1 [Corona, Angela; Distinto, Simona; Esposito, Francesca; Maccioni, Elias; Tramontano, Enzo] Cittadella Univ Monserrato, Dipartimento Sci Vita & Ambiente, SS554, I-09042 Monserrato, Italy.
[Desantis, Jenny; Massari, Serena; Sabatini, Stefano; Manfroni, Giuseppe; Cecchetti, Violetta; Tabarrini, Oriana] Univ Perugia, Dipartimento Sci Farmaceut, Via Liceo 1, I-06123 Perugia, Italy.
[Masaoka, Takashi; Le Grice, Stuart F. J.] NCI, Basic Res Lab, Frederick, MD 21702 USA.
[Pannecouque, Christophe] Katholieke Univ Leuven, Lab Virol & Chemotherapy, Dept Microbiol & Immunol, Rega Inst Med Res, Minderbroedersstr 10, B-3000 Leuven, Belgium.
RP Tramontano, E (reprint author), Cittadella Univ Monserrato, Dipartimento Sci Vita & Ambiente, SS554, I-09042 Monserrato, Italy.; Tabarrini, O (reprint author), Univ Perugia, Dipartimento Sci Farmaceut, Via Liceo 1, I-06123 Perugia, Italy.
EM tramon@unica.it; oriana.tabarrini@unipg.it
RI Esposito, Francesca/I-8879-2012;
OI Esposito, Francesca/0000-0001-9725-7977; Corona,
Angela/0000-0002-6630-8636
NR 52
TC 0
Z9 0
U1 3
U2 3
PU WILEY-V C H VERLAG GMBH
PI WEINHEIM
PA POSTFACH 101161, 69451 WEINHEIM, GERMANY
SN 1860-7179
EI 1860-7187
J9 CHEMMEDCHEM
JI ChemMedChem
PD AUG 19
PY 2016
VL 11
IS 16
SI SI
BP 1709
EP 1720
DI 10.1002/cmdc.201600015
PG 12
WC Chemistry, Medicinal; Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA DW3YT
UT WOS:000383579700007
PM 26990134
ER
PT J
AU Mammoli, V
Bonifazi, A
Dal Ben, D
Giannella, M
Giorgioni, G
Piergentili, A
Pigini, M
Quaglia, W
Thomas, A
Newman, AH
Ferre, S
Sanchez-Soto, M
Keck, TM
Del Bello, F
AF Mammoli, Valerio
Bonifazi, Alessandro
Dal Ben, Diego
Giannella, Mario
Giorgioni, Gianfabio
Piergentili, Alessandro
Pigini, Maria
Quaglia, Wilma
Thomas, Ajiroghene
Newman, Amy H.
Ferre, Sergi
Sanchez-Soto, Marta
Keck, Thomas M.
Del Bello, Fabio
TI A Novel Class of Dopamine D-4 Receptor Ligands Bearing an Imidazoline
Nucleus
SO CHEMMEDCHEM
LA English
DT Article; Proceedings Paper
CT 23rd National Meeting of the Medicinal-Chemistry-Division of the
Italian-Chemical-Society (DCF-SCI)
CY 2015
CL Salerno, ITALY
SP Italian Chem Soc, Med Chem Div
DE D4 receptor antagonists; dopamine; drug design; imidazolines; privileged
structures
ID D3 RECEPTOR; PSYCHIATRIC-DISORDERS; PRIVILEGED STRUCTURES; ERECTILE
DYSFUNCTION; CURRENT PERSPECTIVES; MORPHINE-DEPENDENCE; FORCE-FIELD;
RATS; AGONIST; ANTAGONIST
AB Over the years, the 2-substituted imidazoline nucleus has been demonstrated to be a bioversatile structural motif. In this study, novel imidazoline derivatives bearing a 3- and/or 4-hydroxy- or methoxy-substituted phenyl ring, linked by an ethylene bridge to position2 of an N-benzyl- or N-phenethyl-substituted imidazoline nucleus, were prepared and studied against D-2-like receptor subtypes. Binding studies highlighted that a set of N-phenethylimidazoline compounds are selective for D-4 over D-2 and D-3 receptors. In functional assays, the 3-methoxy-substituted derivative, endowed with the highest D-4 affinity value, and its 3-hydroxy analogue behaved as partial agonists with low intrinsic efficacy and as competitive D-4 antagonists when tested in the presence of the D-2-like receptor agonist quinpirole. Molecular docking analysis, performed using a homology model of the human D-4 receptor developed using the X-ray crystal structure of the antagonist-bound human D-3 receptor as a template, was in accordance with the binding results and provided useful information for the design of novel imidazoline D-4 receptor ligands based on this new scaffold.
C1 [Mammoli, Valerio; Bonifazi, Alessandro; Dal Ben, Diego; Giannella, Mario; Giorgioni, Gianfabio; Piergentili, Alessandro; Pigini, Maria; Quaglia, Wilma; Thomas, Ajiroghene; Del Bello, Fabio] Univ Camerino, Sch Pharm, Med Chem Unit, Via S Agostino 1, I-62032 Camerino, Italy.
[Bonifazi, Alessandro; Newman, Amy H.; Keck, Thomas M.] NIDA, Med Chem Sect, Mol Targets & Medicat Discovery Branch, Intramural Res Program, 333 Cassell Dr, Baltimore, MD 21224 USA.
[Ferre, Sergi; Sanchez-Soto, Marta] NIDA, Integrat Neurobiol Sect, Mol Targets & Medicat Discovery Branch, Intramural Res Program, 333 Cassell Dr, Baltimore, MD 21224 USA.
[Keck, Thomas M.] Rowan Univ, Dept Chem & Biochem, Dept Biomed & Translat Sci, Coll Sci & Math, 201 Mullica Hill Rd, Glassboro, NJ 08028 USA.
RP Del Bello, F (reprint author), Univ Camerino, Sch Pharm, Med Chem Unit, Via S Agostino 1, I-62032 Camerino, Italy.
EM fabio.delbello@unicam.it
RI Ferre, Sergi/K-6115-2014;
OI Ferre, Sergi/0000-0002-1747-1779; Thomas, Ajiroghene/0000-0003-1852-6716
FU Intramural NIH HHS [ZIA DA000424-17]
NR 54
TC 0
Z9 0
U1 3
U2 3
PU WILEY-V C H VERLAG GMBH
PI WEINHEIM
PA POSTFACH 101161, 69451 WEINHEIM, GERMANY
SN 1860-7179
EI 1860-7187
J9 CHEMMEDCHEM
JI ChemMedChem
PD AUG 19
PY 2016
VL 11
IS 16
SI SI
BP 1819
EP 1828
DI 10.1002/cmdc.201600022
PG 10
WC Chemistry, Medicinal; Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA DW3YT
UT WOS:000383579700018
PM 26990230
ER
PT J
AU Lauer, MS
AF Lauer, Michael S.
TI Heart Rate Recovery: Coming Back Full-Circle to the Baroreceptor Reflex
SO CIRCULATION RESEARCH
LA English
DT Editorial Material
DE Editorials; blood pressure; cohort studies; dogs; heart rate; myocardial
infarction
ID TREADMILL EXERCISE; SUDDEN-DEATH; MORTALITY; PREDICTOR; DISEASE
C1 [Lauer, Michael S.] NIH, Off Extramural Res, One Ctr Dr,Bldg 1,Room 144, Bethesda, MD 20892 USA.
RP Lauer, MS (reprint author), NIH, Off Extramural Res, One Ctr Dr,Bldg 1,Room 144, Bethesda, MD 20892 USA.
EM michael.lauer@nih.gov
FU Intramural NIH HHS [Z99 OD999999]
NR 13
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 AUG 19
PY 2016
VL 119
IS 5
BP 582
EP 583
DI 10.1161/CIRCRESAHA.116.309392
PG 2
WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular
Disease
SC Cardiovascular System & Cardiology; Hematology
GA DV9RN
UT WOS:000383279000005
PM 27539969
ER
PT J
AU Maric-Bilkan, C
Galis, ZS
AF Maric-Bilkan, Christine
Galis, Zorina S.
TI Trends in NHLBI-Funded Research on Sex Differences in Hypertension
SO CIRCULATION RESEARCH
LA English
DT Article
DE blood pressure; cardiovascular disease; hypertension; research; sex
hormones
ID AMERICAN-HEART-ASSOCIATION; II-INDUCED HYPERTENSION; T-CELL; DISEASE;
UPDATE
AB Although sex differences in blood pressure levels and the prevalence of hypertension are well recognized, the mechanisms responsible for this sexual dimorphism remain poorly understood. To gain a better understanding of the research funding trends in the field of sex differences related to hypertension and the main research topics funded by the National Heart, Lung, and Blood Institute (NHLBI), we analyzed the entire NHLBI award portfolio between fiscal years (FYs) 1991 to 2014. Using specific search terms to define "sex differences," we interrogated the publicly available list of NHLBI-funded awards active in FY1991 to FY2014 in the National Institutes of Health (NIH) Research Portfolio Online Reporting (RePORTER) database. We further analyzed and categorized awards according to a disease focus and whether each award was directly focused on comparing males versus females, or examining the effects of sex hormones in either sex. The number of NHLBI awards related to " sex differences in hypertension" progressively increased from FY1991 to FY2014, for a cumulative total of 486 awards during the entire period analyzed. The overall dollar investment has also progressively increased from $0.5 million (FY1991) to $18.3 million (FY2014), for a cumulative total of $187 million during FY1991 to FY2014. When compared with global funding trends, NHLBI seems to be the largest funder of research on " sex differences in hypertension" in the world. Importantly, the increased NHLBI investment in sex differences in hypertension research has enabled the investigation of an increased diversity of scientific topics. Although NHLBI is funding an increasing number of awards related to " sex differences in hypertension," there are still many unanswered questions related to the mechanisms underlying this disparity.
C1 [Maric-Bilkan, Christine; Galis, Zorina S.] NHLBI, NIH, Div Cardiovasc Sci, Vasc Biol & Hypertens Branch, 6701 Rockledge Dr,Room 8110, Bethesda, MD 20892 USA.
RP Maric-Bilkan, C (reprint author), NHLBI, NIH, Div Cardiovasc Sci, Vasc Biol & Hypertens Branch, 6701 Rockledge Dr,Room 8110, Bethesda, MD 20892 USA.
EM christine.maric-bilkan@nih.gov
NR 12
TC 0
Z9 0
U1 3
U2 3
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 AUG 19
PY 2016
VL 119
IS 5
BP 591
EP 595
DI 10.1161/CIRCRESAHA.116.308963
PG 5
WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular
Disease
SC Cardiovascular System & Cardiology; Hematology
GA DV9RN
UT WOS:000383279000008
PM 27539972
ER
PT J
AU Schmidt, T
Ye, F
Situ, AJ
An, W
Ginsberg, MH
Ulmer, TS
AF Schmidt, Thomas
Ye, Feng
Situ, Alan J.
An, Woojin
Ginsberg, Mark H.
Ulmer, Tobias S.
TI A Conserved Ectodomain-Transmembrane Domain Linker Motif Tunes the
Allosteric Regulation of Cell Surface Receptors
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
DE allosteric regulation; cytokine; integrin; isothermal titration
calorimetry (ITC); nuclear magnetic resonance (NMR); protein dynamics;
receptor signaling; transmembrane cell surface receptors
ID GROWTH-FACTOR RECEPTOR; INTEGRIN ACTIVATION; DIPOLAR COUPLINGS; PROTEIN
STRUCTURES; MEMBRANE-PROTEINS; CRYSTAL-STRUCTURE; NMR-SPECTROSCOPY;
CHEMICAL-SHIFTS; ALPHA-SUBUNIT; COMPLEX
AB In many families of cell surface receptors, a single transmembrane (TM) -helix separates ecto- and cytosolic domains. A defined coupling of ecto- and TM domains must be essential to allosteric receptor regulation but remains little understood. Here, we characterize the linker structure, dynamics, and resulting ecto-TM domain coupling of integrin IIb in model constructs and relate it to other integrin subunits by mutagenesis. Cellular integrin activation assays subsequently validate the findings in intact receptors. Our results indicate a flexible yet carefully tuned ecto-TM coupling that modulates the signaling threshold of integrin receptors. Interestingly, a proline at the N-terminal TM helix border, termed NBP, is critical to linker flexibility in integrins. NBP is further predicted in 21% of human single-pass TM proteins and validated in cytokine receptors by the TM domain structure of the cytokine receptor common subunit and its P441A-substituted variant. Thus, NBP is a conserved uncoupling motif of the ecto-TM domain transition and the degree of ecto-TM domain coupling represents an important parameter in the allosteric regulation of diverse cell surface receptors.
C1 [Schmidt, Thomas; Situ, Alan J.; Ulmer, Tobias S.] Univ Southern Calif, Keck Sch Med, Dept Biochem & Mol Biol, Los Angeles, CA 90033 USA.
[Schmidt, Thomas; Situ, Alan J.; Ulmer, Tobias S.] Univ Southern Calif, Keck Sch Med, Zilkha Neurogenet Inst, Los Angeles, CA 90033 USA.
[Ye, Feng; Ginsberg, Mark H.] Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA.
[An, Woojin] Univ Southern Calif, Dept Biochem & Mol Biol, Los Angeles, CA 90033 USA.
[An, Woojin] Univ Southern Calif, Norris Comprehens Canc Ctr, Los Angeles, CA 90033 USA.
[Schmidt, Thomas] NIDDK, Chem Phys Lab, NIH, Bldg 2, Bethesda, MD 20892 USA.
RP Ulmer, TS (reprint author), 1501 San Pablo St,ZNI 111, Los Angeles, CA 90033 USA.
EM tulmer@usc.edu
FU American Heart Association [15GRNT23200010]; National Institutes of
Health [HL31950, HL078784, HL117807]
FX This work was supported by American Heart Association Grant
15GRNT23200010 (to T. S. U.) and National Institutes of Health Grants
HL31950, HL078784, and HL117807 (to M. H. G.). 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 60
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U1 3
U2 3
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 AUG 19
PY 2016
VL 291
IS 34
BP 17536
EP 17546
DI 10.1074/jbc.M116.733683
PG 11
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA DV9DX
UT WOS:000383241300006
PM 27365391
ER
PT J
AU Zhou, BY
Ritt, DA
Morrison, DK
Der, CJ
Cox, AD
AF Zhou, Bingying
Ritt, Daniel A.
Morrison, Deborah K.
Der, Channing J.
Cox, Adrienne D.
TI Protein Kinase CK2 Maintains Extracellular Signal-regulated Kinase (ERK)
Activity in a CK2 Kinase-independent Manner to Promote Resistance to
Inhibitors of RAF and MEK but Not ERK in BRAF Mutant Melanoma
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
DE drug resistance; dual specificity phosphoprotein phosphatase;
extracellular signal-regulated kinase (ERK); melanoma; Ras protein; CK2;
kinase suppressor of RAS 1 (KSR1)
ID PANCREATIC-CANCER; ACTIVATION; CK2-ALPHA; CELLS; PHOSPHORYLATES;
CARCINOMA; SURVIVAL; LEUKEMIA; COMPLEX
AB The protein kinase casein kinase 2 (CK2) is a pleiotropic and constitutively active kinase that plays crucial roles in cellular proliferation and survival. Overexpression of CK2, particularly the catalytic subunit (CK2, CSNK2A1), has been implicated in a wide variety of cancers and is associated with poorer survival and resistance to both conventional and targeted anticancer therapies. Here, we found that CK2 protein is elevated in melanoma cell lines compared with normal human melanocytes. We then tested the involvement of CK2 in drug resistance to Food and Drug Administration-approved single agent targeted therapies for melanoma. In BRAF mutant melanoma cells, ectopic CK2 decreased sensitivity to vemurafenib (BRAF inhibitor), dabrafenib (BRAF inhibitor), and trametinib (MEK inhibitor) by a mechanism distinct from that of mutant NRAS. Conversely, knockdown of CK2 sensitized cells to inhibitor treatment. CK2-mediated RAF-MEK kinase inhibitor resistance was tightly linked to its maintenance of ERK phosphorylation. We found that CK2 post-translationally regulates the ERK-specific phosphatase dual specificity phosphatase 6 (DUSP6) in a kinase dependent-manner, decreasing its abundance. However, we unexpectedly showed, by using a kinase-inactive mutant of CK2, that RAF-MEK inhibitor resistance did not rely on CK2 kinase catalytic function, and both wild-type and kinase-inactive CK2 maintained ERK phosphorylation upon inhibition of BRAF or MEK. That both wild-type and kinase-inactive CK2 bound equally well to the RAF-MEK-ERK scaffold kinase suppressor of Ras 1 (KSR1) suggested that CK2 increases KSR facilitation of ERK phosphorylation. Accordingly, CK2 did not cause resistance to direct inhibition of ERK by the ERK1/2-selective inhibitor SCH772984. Our findings support a kinase-independent scaffolding function of CK2 that promotes resistance to RAF- and MEK-targeted therapies.
C1 [Zhou, Bingying; Der, Channing J.; Cox, Adrienne D.] Univ N Carolina, Dept Pharmacol, Chapel Hill, NC 27599 USA.
[Der, Channing J.; Cox, Adrienne D.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA.
[Cox, Adrienne D.] Univ N Carolina, Dept Radiat Oncol, Chapel Hill, NC 27599 USA.
[Ritt, Daniel A.; Morrison, Deborah K.] NCI, Lab Cell & Dev Signaling, Ctr Canc Res, NIH, Frederick, MD 21702 USA.
RP Cox, AD (reprint author), Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA.
EM adrienne_cox@med.unc.edu
FU National Institutes of Health [CA042978, CA179193, CA199235]; NCI [ZIA
BC 010329]; Pancreatic Cancer Action Network-American Association for
Cancer Research
FX This work was supported by National Institutes of Health Grants
CA042978, CA179193, and CA199235 (to A. D. C. and C. J. D.) and ZIA BC
010329 from the NCI (to D. K. M. and D. A. R.) and by the Pancreatic
Cancer Action Network-American Association for Cancer Research (to A. D.
C. and C. J. D.). 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 7
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 AUG 19
PY 2016
VL 291
IS 34
BP 17804
EP 17815
DI 10.1074/jbc.M115.712885
PG 12
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA DV9DX
UT WOS:000383241300027
PM 27226552
ER
PT J
AU Atwood, BL
Woolnough, JL
Lefevre, GM
Ribeiro, MS
Felsenfeld, G
Giles, KE
AF Atwood, Blake L.
Woolnough, Jessica L.
Lefevre, Gaelle M.
Ribeiro, Mariana Saint Just
Felsenfeld, Gary
Giles, Keith E.
TI Human Argonaute 2 Is Tethered to Ribosomal RNA through MicroRNA
Interactions
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
DE Argonaute; ChIP-sequencing (ChIP-seq); Dicer; microRNA (miRNA);
ribosomal ribonucleic acid (rRNA) (ribosomal RNA); miRNA; par-clip; rRNA
ID HUMAN-CELLS; GENE-EXPRESSION; BINDING-SITES; POLYMERASE I; PAR-CLIP;
TARGET; NUCLEOLUS; PROTEIN; HETEROCHROMATIN; DICER
AB The primary role of the RNAi machinery is to promote mRNA degradation within the cytoplasm in a microRNA-dependent manner. However, both Dicer and the Argonaute protein family have expanded roles in gene regulation within the nucleus. To further our understanding of this role, we have identified chromatin binding sites for AGO2 throughout the 45S region of the human rRNA gene. The location of these sites was mirrored by the positions of AGO2 cross-linking sites identified via PAR-CLIP-seq. AGO2 binding to the rRNA within the nucleus was confirmed by RNA immunoprecipitation and quantitative-PCR. To explore a possible mechanism by which AGO2 could be recruited to the rRNA, we identified 1174 regions within the 45S rRNA transcript that have the ability to form a perfect duplex with position 2-6 (seed sequence) of each microRNA expressed in HEK293T cells. Of these potential AGO2 binding sites, 479 occurred within experimentally verified AGO2-rRNA cross-linking sites. The ability of AGO2 to cross-link to rRNA was almost completely lost in a DICER knock-out cell line. The transfection of miR-92a-2-3p into the noDICE cell line facilitated AGO2 cross-linking at a region of the rRNA that has a perfect seed match at positions 3-8, including a single G-U base pair. Knockdown of AGO2 within HEK293T cells causes a slight, but statistically significant increase in the overall rRNA synthesis rate but did not impact the ratio of processing intermediates or the recruitment of the Pol I transcription factor UBTF.
C1 [Atwood, Blake L.; Woolnough, Jessica L.; Ribeiro, Mariana Saint Just; Giles, Keith E.] Univ Alabama Birmingham, UAB Stem Cell Inst, Dept Biochem & Mol Genet, Birmingham, AL 35209 USA.
[Lefevre, Gaelle M.; Felsenfeld, Gary] NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Giles, KE (reprint author), Univ Alabama Birmingham, UAB Stem Cell Inst, Dept Biochem & Mol Genet, Birmingham, AL 35209 USA.
EM kegiles@uab.edu
FU National Institutes of Health, NIDDK Intramural Research Program
FX This work was supported in part by the National Institutes of Health,
NIDDK Intramural Research Program. 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 60
TC 0
Z9 0
U1 6
U2 6
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 AUG 19
PY 2016
VL 291
IS 34
BP 17919
EP 17928
DI 10.1074/jbc.M116.725051
PG 10
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA DV9DX
UT WOS:000383241300035
PM 27288410
ER
PT J
AU Tatusova, T
DiCuccio, M
Badretdin, A
Chetvernin, V
Nawrocki, EP
Zaslavsky, L
Lomsadze, A
Pruitt, K
Borodovsky, M
Ostell, J
AF Tatusova, Tatiana
DiCuccio, Michael
Badretdin, Azat
Chetvernin, Vyacheslav
Nawrocki, Eric P.
Zaslavsky, Leonid
Lomsadze, Alexandre
Pruitt, Kimd.
Borodovsky, Mark
Ostell, James
TI NCBI prokaryotic genome annotation pipeline
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID MICROBIAL GENOMES; PAN-GENOME; DATABASE; PREDICTION; CLASSIFICATION;
RESOURCES
AB Recent technological advances have opened unprecedented opportunities for large-scale sequencing and analysis of populations of pathogenic species in disease outbreaks, as well as for large-scale diversity studies aimed at expanding our knowledge across the whole domain of prokaryotes. To meet the challenge of timely interpretation of structure, function and meaning of this vast genetic information, a comprehensive approach to automatic genome annotation is critically needed. In collaboration with Georgia Tech, NCBI has developed a new approach to genome annotation that combines alignment based methods with methods of predicting protein-coding and RNA genes and other functional elements directly from sequence. A new gene finding tool, GeneMarkS+, uses the combined evidence of protein and RNA placement by homology as an initial map of annotation to generate and modify ab initio gene predictions across the whole genome. Thus, the new NCBI's Prokaryotic Genome Annotation Pipeline (PGAP) relies more on sequence similarity when confident comparative data are available, while it relies more on statistical predictions in the absence of external evidence. The pipeline provides a framework for generation and analysis of annotation on the full breadth of prokaryotic taxonomy. For additional information on PGAP see https://www.ncbi.nlm.nih.gov/genome/annotation prok/ and the NCBI Handbook, https://www.ncbi.nlm.nih.gov/books/NBK174280/.
C1 [Tatusova, Tatiana; DiCuccio, Michael; Badretdin, Azat; Chetvernin, Vyacheslav; Nawrocki, Eric P.; Zaslavsky, Leonid; Pruitt, Kimd.; Ostell, James] US Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA.
[Lomsadze, Alexandre; Borodovsky, Mark] Georgia Tech, Wallace H Coulter Dept Biomed Engn, Atlanta, GA 30332 USA.
[Borodovsky, Mark] Georgia Tech, Sch Computat Sci & Engn, Atlanta, GA 30332 USA.
RP Borodovsky, M (reprint author), Georgia Tech, Wallace H Coulter Dept Biomed Engn, Atlanta, GA 30332 USA.; Borodovsky, M (reprint author), Georgia Tech, Sch Computat Sci & Engn, Atlanta, GA 30332 USA.
EM borodovsky@gatech.edu
FU Intramural Research Program of the NIH National Library of Medicine; NIH
[HG000783]
FX Intramural Research Program of the NIH National Library of Medicine (in
part); the work of M.B. and A.L. was supported in part by NIH grant
HG000783 to M.B. Funding for open access charge: Intramural Research
Program of the NIH National Library of Medicine.
NR 36
TC 15
Z9 15
U1 6
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 AUG 19
PY 2016
VL 44
IS 14
BP 6614
EP 6624
DI 10.1093/nar/gkw569
PG 11
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA DV5VX
UT WOS:000382999900013
PM 27342282
ER
PT J
AU Arbel-Goren, R
Tal, A
Parasar, B
Dym, A
Costantino, N
Munoz-Garcia, J
Court, DL
Stavans, J
AF Arbel-Goren, Rinat
Tal, Asaf
Parasar, Bibudha
Dym, Alvah
Costantino, Nina
Munoz-Garcia, Javier
Court, Donald L.
Stavans, Joel
TI Transcript degradation and noise of small RNA-controlled genes in a
switch activated network in Escherichia coli
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID BACTERIAL SMALL RNAS; RYHB SMALL RNA; SMALL REGULATORY RNAS;
MESSENGER-RNA; NONCODING RNA; PHENOTYPIC NOISE; IRON HOMEOSTASIS;
HFQ-BINDING; EXPRESSION; TARGETS
AB Post-transcriptional regulatory processes may change transcript levels and affect cell-to-cell variability or noise. We study small-RNA downregulation to elucidate its effects on noise in the iron homeostasis network of Escherichia coli. In this network, the small-RNA RyhB undergoes stoichiometric degradation with the transcripts of target genes in response to iron stress. Using single-molecule fluorescence in situ hybridization, we measured transcript numbers of the RyhB-regulated genes sodB and fumA in individual cells as a function of iron deprivation. We observed a monotonic increase of noise with iron stress but no evidence of theoretically predicted, enhanced stoichiometric fluctuations in transcript numbers, nor of bistable behavior in transcript distributions. Direct detection of RyhB in individual cells shows that its noise is much smaller than that of these two targets, when RyhB production is significant. A generalized two-state model of bursty transcription that neglects RyhB fluctuations describes quantitatively the dependence of noise and transcript distributions on iron deprivation, enabling extraction of in vivo RyhB-mediated transcript degradation rates. The transcripts' threshold-linear behavior indicates that the effective in vivo interaction strength between RyhB and its two target transcripts is comparable. Strikingly, the bacterial cell response exhibits Furdependent, switch-like activation instead of a graded response to iron deprivation.
C1 [Arbel-Goren, Rinat; Tal, Asaf; Parasar, Bibudha; Dym, Alvah; Munoz-Garcia, Javier; Stavans, Joel] Weizmann Inst Sci, Dept Phys Complex Syst, IL-76100 Rehovot, Israel.
[Costantino, Nina; Court, Donald L.] NCI, Gene Regulat & Chromosome Biol Lab, Frederick, MD 21702 USA.
[Munoz-Garcia, Javier] Univ Carlos III Madrid, Dept Matemat, Ave Univ 30, Madrid 28911, Spain.
[Munoz-Garcia, Javier] Univ Carlos III Madrid, GISC, Ave Univ 30, Madrid 28911, Spain.
RP Stavans, J (reprint author), Weizmann Inst Sci, Dept Phys Complex Syst, IL-76100 Rehovot, Israel.; Court, DL (reprint author), NCI, Gene Regulat & Chromosome Biol Lab, Frederick, MD 21702 USA.
EM courtd@mail.nih.gov; joel.stavans@weizmann.ac.il
RI Munoz-Garcia, Javier/C-1135-2011
OI Munoz-Garcia, Javier/0000-0002-7594-9507
FU Israel Science Foundation [514415]; Feinberg Foundation Visiting Faculty
Program; MICINN (Spain) [FIS2012-32349]; Intramural Research Program of
the National Institutes of Health; National Cancer Institute; Center for
Cancer Research; Siegfried and Irma Ullman Professorial Chair
FX Israel Science Foundation [514415 to J.S.]; Feinberg Foundation Visiting
Faculty Program (to J.M.-G.); MICINN (Spain) [FIS2012-32349 to J.M.-G.];
Intramural Research Program of the National Institutes of Health (to
D.L.C.); National Cancer Institute (to D.L.C.); Center for Cancer
Research (to D.L.C.); Siegfried and Irma Ullman Professorial Chair (to
J.S.). Funding for open access charge: Israel Science Foundation.
NR 73
TC 1
Z9 1
U1 5
U2 6
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 AUG 19
PY 2016
VL 44
IS 14
BP 6707
EP 6720
DI 10.1093/nar/gkw273
PG 14
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA DV5VX
UT WOS:000382999900020
PM 27085802
ER
PT J
AU Ni, T
Yang, WJ
Han, M
Zhang, YB
Shen, T
Nie, HB
Zhou, ZH
Dai, YL
Yang, YQ
Liu, PC
Cui, KR
Zeng, ZH
Tian, Y
Zhou, B
Wei, G
Zhao, KJ
Peng, WQ
Zhu, J
AF Ni, Ting
Yang, Wenjing
Han, Miao
Zhang, Yubo
Shen, Ting
Nie, Hongbo
Zhou, Zhihui
Dai, Yalei
Yang, Yanqin
Liu, Poching
Cui, Kairong
Zeng, Zhouhao
Tian, Yi
Zhou, Bin
Wei, Gang
Zhao, Keji
Peng, Weiqun
Zhu, Jun
TI Global intron retention mediated gene regulation during CD4(+) T cell
activation
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID CO-TRANSCRIPTIONAL REGULATION; HUMAN GENOME; DNA METHYLATION;
COORDINATED REGULATION; HISTONE MODIFICATION; CHROMATIN-STATE; RNA;
DIFFERENTIATION; EXPRESSION; PATHWAYS
AB T cell activation is a well-established model for studying cellular responses to exogenous stimulation. Using strand-specific RNA-seq, we observed that intron retention is prevalent in polyadenylated transcripts in resting CD4(+) T cells and is significantly reduced upon T cell activation. Several lines of evidence suggest that intron-retained transcripts are less stable than fully spliced transcripts. Strikingly, the decrease in intron retention (IR) levels correlate with the increase in steady-state mRNA levels. Further, the majority of the genes upregulated in activated T cells are accompanied by a significant reduction in IR. Of these 1583 genes, 185 genes are predominantly regulated at the IR level, and highly enriched in the proteasome pathway, which is essential for proper T cell proliferation and cytokine release. These observations were corroborated in both human and mouse CD4(+) T cells. Our study revealed a novel post-transcriptional regulatory mechanism that may potentially contribute to coordinated and/or quick cellular responses to extracellular stimuli such as an acute infection.
C1 [Ni, Ting; Han, Miao; Shen, Ting; Nie, Hongbo; Zhou, Bin; Wei, Gang] Fudan Univ, Sch Life Sci, Collaborat Innovat Ctr Genet & Dev, State Key Lab Genet Engn, Shanghai 200438, Peoples R China.
[Ni, Ting; Han, Miao; Shen, Ting; Nie, Hongbo; Zhou, Bin; Wei, Gang] Fudan Univ, Sch Life Sci, Collaborat Innovat Ctr Genet & Dev, MOE Key Lab Contemporary Anthropol, Shanghai 200438, Peoples R China.
[Yang, Wenjing; Zhang, Yubo; Yang, Yanqin; Liu, Poching; Cui, Kairong; Zhao, Keji; Zhu, Jun] NHLBI, Syst Biol Ctr, NIH, Bldg 10, Bethesda, MD 20892 USA.
[Zhou, Zhihui; Dai, Yalei] Tongji Univ, Sch Med, Dept Immunol, Shanghai 200092, Peoples R China.
[Zeng, Zhouhao; Tian, Yi; Peng, Weiqun] George Washington Univ, Dept Phys, Washington, DC 20052 USA.
[Tian, Yi] Third Mil Med Univ, PLA, Inst Immunol, Chongqing 400038, Peoples R China.
RP Ni, T (reprint author), Fudan Univ, Sch Life Sci, Collaborat Innovat Ctr Genet & Dev, State Key Lab Genet Engn, Shanghai 200438, Peoples R China.; Ni, T (reprint author), Fudan Univ, Sch Life Sci, Collaborat Innovat Ctr Genet & Dev, MOE Key Lab Contemporary Anthropol, Shanghai 200438, Peoples R China.; Zhu, J (reprint author), NHLBI, Syst Biol Ctr, NIH, Bldg 10, Bethesda, MD 20892 USA.; Peng, WQ (reprint author), George Washington Univ, Dept Phys, Washington, DC 20052 USA.
EM tingni@fudan.edu.cn; wpeng@gwu.edu; jun.zhu@nih.gov
FU National Institute of Health (NIH) [Division of Intramural Research of
National Heart Lung and Blood Institute] [1R21AI113806]; National Key
Basic Research Program of China [973 programs] [2013CB530700,
2015CB943000, 2012CB518700]; National Science Foundation of China
[31271348, 31471192]; Innovation Project of Shanghai Municipal Education
Commission [14ZZ007]; Thousand Talents Plan of China; 111 Project of
China [B13016]
FX National Institute of Health (NIH) [Division of Intramural Research of
National Heart Lung and Blood Institute to K. Z. and J. Z.; 1R21AI113806
to W. P.]; National Key Basic Research Program of China [973 programs:
2013CB530700 and 2015CB943000 to T. N., 2012CB518700 to Y. D.]; National
Science Foundation of China [31271348 and 31471192 to T. N.]; Innovation
Project of Shanghai Municipal Education Commission [14ZZ007 to T. N.];
Thousand Talents Plan of China and the 111 Project of China (B13016).
NR 61
TC 2
Z9 2
U1 8
U2 9
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 AUG 19
PY 2016
VL 44
IS 14
BP 6817
EP 6829
DI 10.1093/nar/gkw591
PG 13
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA DV5VX
UT WOS:000382999900029
PM 27369383
ER
PT J
AU Metifiot, M
Johnson, BC
Kiselev, E
Marler, L
Zhao, XZ
Burke, TR
Marchand, C
Hughes, SH
Pommier, Y
AF Metifiot, Mathieu
Johnson, Barry C.
Kiselev, Evgeny
Marler, Laura
Zhao, Xue Zhi
Burke, Terrence R., Jr.
Marchand, Christophe
Hughes, Stephen H.
Pommier, Yves
TI Selectivity for strand-transfer over 3 '-processing and susceptibility
to clinical resistance of HIV-1 integrase inhibitors are driven by key
enzyme-DNA interactions in the active site
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID VIRAL-DNA; MOLECULAR-DYNAMICS; CROSS-RESISTANCE; FLEXIBLE LOOP;
IN-VITRO; RALTEGRAVIR; ELVITEGRAVIR; BINDING; MUTANTS; DOLUTEGRAVIR
AB Integrase strand transfer inhibitors (INSTIs) are highly effective against HIV infections. Co-crystal structures of the prototype foamy virus intasome have shown that all three FDA-approved drugs, raltegravir (RAL), elvitegravir and dolutegravir (DTG), act as interfacial inhibitors during the strand transfer (ST) integration step. However, these structures give only a partial sense for the limited inhibition of the 3'-processing reaction by INSTIs and how INSTIs can be modified to overcome drug resistance, notably against the G140S-Q148H double mutation. Based on biochemical experiments with modified oligonucleotides, we demonstrate that both the viral DNA + 1 and -1 bases, which flank the 3'-processing site, play a critical role for 3'-processing efficiency and inhibition by RAL and DTG. In addition, the G140S-Q148H (SH) mutant integrase, which has a reduced 3'-processing activity, becomes more active and more resistant to inhibition of 3'-processing by RAL and DTG in the absence of the -1 and + 1 bases. Molecular modeling of HIV-1 integrase, together with biochemical data, indicate that the conserved residue Q146 in the flexible loop of HIV-1 integrase is critical for productive viral DNA binding through specific contacts with the virus DNA ends in the 3'-processing and ST reactions. The potency of integrase inhibitors against 3'-processing and their ability to overcome resistance is discussed.
C1 [Metifiot, Mathieu; Kiselev, Evgeny; Marler, Laura; Marchand, Christophe; Pommier, Yves] NCI, Dev Therapeut Branch, Ctr Canc Res, NIH, 37 Convent Dr, Bethesda, MD 20892 USA.
[Metifiot, Mathieu; Kiselev, Evgeny; Marler, Laura; Marchand, Christophe; Pommier, Yves] NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, 37 Convent Dr, Bethesda, MD 20892 USA.
[Johnson, Barry C.; Hughes, Stephen H.] NCI, HIV Dynam & Replicat Program, Ctr Canc Res, NIH, Frederick, MD 21702 USA.
[Zhao, Xue Zhi; Burke, Terrence R., Jr.] NCI, Biol Chem Lab, Ctr Canc Res, NIH, Frederick, MD 21702 USA.
[Metifiot, Mathieu] Univ Bordeaux, Lab Microbiol Fondamentale & Pathogen, CNRS UMR 5234, 146 Rue Leo Saignat, F-33076 Bordeaux, France.
RP Metifiot, M; Pommier, Y (reprint author), NCI, Dev Therapeut Branch, Ctr Canc Res, NIH, 37 Convent Dr, Bethesda, MD 20892 USA.; Metifiot, M; Pommier, Y (reprint author), NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, 37 Convent Dr, Bethesda, MD 20892 USA.; Metifiot, M (reprint author), Univ Bordeaux, Lab Microbiol Fondamentale & Pathogen, CNRS UMR 5234, 146 Rue Leo Saignat, F-33076 Bordeaux, France.
EM mathieu.metifiot@u-bordeaux.fr; pommier@nih.gov
FU Intramural Program of the National Cancer Institute; Center for Cancer
Research [Z01 BC 007333, ZIA BC 007363]; Intramural AIDS Targeted
Antiviral Program (IATAP); National Institutes of Health; Developmental
Therapeutics Branch; Laboratory of Molecular Pharmacology; CCR/NCI/NIH
FX Intramural Program of the National Cancer Institute; Center for Cancer
Research [Z01 BC 007333, ZIA BC 007363]; Intramural AIDS Targeted
Antiviral Program (IATAP); National Institutes of Health. Funding for
open access charge: Developmental Therapeutics Branch; Laboratory of
Molecular Pharmacology; CCR/NCI/NIH.
NR 47
TC 0
Z9 0
U1 5
U2 5
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 AUG 19
PY 2016
VL 44
IS 14
BP 6896
EP 6906
DI 10.1093/nar/gkw592
PG 11
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA DV5VX
UT WOS:000382999900035
PM 27369381
ER
PT J
AU Lee, HJ
Gottesman, S
AF Lee, Hyun-Jung
Gottesman, Susan
TI sRNA roles in regulating transcriptional regulators: Lrp and SoxS
regulation by sRNAs
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID TRANSPORTER MESSENGER-RNAS; OXIDATIVE STRESS REGULON; BINDING SMALL
RNAS; GCVB SMALL RNA; COLI CRP GENE; ESCHERICHIA-COLI; H-NS; GLOBAL
REGULATOR; LIPOPOLYSACCHARIDE MODIFICATION; POSTTRANSCRIPTIONAL
REGULATION
AB Post-transcriptional regulation of transcription factors contributes to regulatory circuits. We created translational reporter fusions for multiple central regulators in Escherichia coli and examined the effect of Hfq-dependent non-coding RNAs on these fusions. This approach yields an 'RNA landscape,' identifying Hfq-dependent sRNAs that regulate a given fusion. No significant sRNA regulation of crp or fnr was detected. hns was regulated only by DsrA, as previously reported. Lrp and SoxS were both found to be regulated post-transcriptionally. Lrp, 'leucineresponsive regulatory protein,' regulates genes involved in amino acid biosynthesis and catabolism and other cellular functions. sRNAs DsrA, MicF and GcvB each independently downregulate thelrp translational fusion, confirming previous reports for MicF and GcvB. MicF and DsrA interact with an overlapping site early in the lrp ORF, while GcvB acts upstream at two independent sites in the long lrp leader. Surprisingly, GcvB was found to be responsible for significant downregulation of lrp after oxidative stress; MicF also contributed. SoxS, an activator of genes used to combat oxidative stress, is negatively regulated by sRNA MgrR. This study demonstrates that while not all global regulators are subject to sRNA regulation, post-transcriptional control by sRNAs allows multiple environmental signals to affect synthesis of the transcriptional regulator.
C1 [Lee, Hyun-Jung; Gottesman, Susan] NCI, Mol Biol Lab, NIH, Bldg 37, Bethesda, MD 20892 USA.
[Lee, Hyun-Jung] Ajou Univ, Sch Med, Dept Biomed Sci, Suwon 443380, South Korea.
RP Gottesman, S (reprint author), NCI, Mol Biol Lab, NIH, Bldg 37, Bethesda, MD 20892 USA.
EM Gottesms@helix.nih.gov
FU Intramural Research Program of the National Institutes of Health,
National Cancer Institute, Center for Cancer Research
FX Intramural Research Program of the National Institutes of Health,
National Cancer Institute, Center for Cancer Research. Funding for open
access charge: Center for Cancer Research intramural funding.
NR 83
TC 4
Z9 4
U1 5
U2 5
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 AUG 19
PY 2016
VL 44
IS 14
BP 6907
EP 6923
DI 10.1093/nar/gkw358
PG 17
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA DV5VX
UT WOS:000382999900036
PM 27137887
ER
PT J
AU Hao, Y
Updegrove, TB
Livingston, NN
Storz, G
AF Hao, Yue
Updegrove, Taylor B.
Livingston, Natasha N.
Storz, Gisela
TI Protection against deleterious nitrogen compounds: role of
sigma(S)-dependent small RNAs encoded adjacent to sdiA
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID SMALL NONCODING RNA; ESCHERICHIA-COLI; MESSENGER-RNA; SOLUBLE-RNA;
OUTER-MEMBRANE; REGULATORY RNAS; GENE-EXPRESSION; E. COLI; HFQ; RPOS
AB Here, we report the characterization of a set of small, regulatory RNAs (sRNAs) expressed from an Escherichia coli locus we have denoted sdsN located adjacent to the LuxR-homolog gene sdiA. Two longer sRNAs, SdsN(137) and SdsN(178) are transcribed from two sigma(S)-dependent promoters but share the same terminator. Low temperature, rich nitrogen sources and the Crl and NarP transcription factors differentially affect the levels of the SdsN transcripts. Whole genome expression analysis after pulse overexpression of SdsN(137) and assays of lacZ fusions revealed that the SdsN(137) directly represses the synthesis of the nitroreductase NfsA, which catalyzes the reduction of the nitrogroup (NO2) in nitroaromatic compounds and the flavohemoglobin HmpA, which has aerobic nitric oxide (NO) dioxygenase activity. Consistent with this regulation, SdsN(137) confers resistance to nitrofurans. In addition, SdsN(137) negatively regulates synthesis of NarP. Interestingly, SdsN(178) is defective at regulating the above targets due to unusual binding to the Hfq protein, but cleavage leads to a shorter form, SdsN(124), able to repress nfsA and hmpA.
C1 [Hao, Yue; Updegrove, Taylor B.; Livingston, Natasha N.; Storz, Gisela] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Mol & Cellular Biol, Bethesda, MD 20892 USA.
[Hao, Yue] Chinese Acad Agr Sci, Inst Apicultural Res, Beijing 100093, Peoples R China.
[Updegrove, Taylor B.] NCI, Mol Biol Lab, Bldg 37, Bethesda, MD 20892 USA.
[Livingston, Natasha N.] US FDA, Ctr Tobacco Prod, Silver Spring, MD 20993 USA.
RP Storz, G (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Mol & Cellular Biol, Bethesda, MD 20892 USA.
EM storz@helix.nih.gov
FU Intramural Research Program of the Eunice Kennedy Shriver National
Institute of Child Health and Human Development; ZIA [HD001608]
FX Intramural Research Program of the Eunice Kennedy Shriver National
Institute of Child Health and Human Development. Funding for open access
charge: ZIA [HD001608].
NR 51
TC 2
Z9 2
U1 1
U2 1
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 AUG 19
PY 2016
VL 44
IS 14
BP 6935
EP 6948
DI 10.1093/nar/gkw404
PG 14
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA DV5VX
UT WOS:000382999900038
PM 27166377
ER
PT J
AU Agrawal, AS
Ying, TL
Tao, XR
Garron, T
Algaissi, A
Wang, YP
Wang, LL
Peng, BH
Jiang, SB
Dimitrov, DS
Tseng, CTK
AF Agrawal, Anurodh Shankar
Ying, Tianlei
Tao, Xinrong
Garron, Tania
Algaissi, Abdullah
Wang, Yanping
Wang, Lili
Peng, Bi-Hung
Jiang, Shibo
Dimitrov, Dimiter S.
Tseng, Chien-Te K.
TI Passive Transfer of A Germline-like Neutralizing Human Monoclonal
Antibody Protects Transgenic Mice Against Lethal Middle East Respiratory
Syndrome Coronavirus Infection
SO SCIENTIFIC REPORTS
LA English
DT Article
ID RECEPTOR-BINDING DOMAIN; PIPISTRELLUS BAT CORONAVIRUS; MERS-COV
INFECTION; SPIKE PROTEIN; MOUSE MODEL; POSTEXPOSURE EFFICACY; DROMEDARY
CAMELS; SAUDI-ARABIA; BETACORONAVIRUS; TRANSMISSION
AB Middle East Respiratory Syndrome coronavirus (MERS-CoV) has repeatedly caused outbreaks in the Arabian Peninsula. To date, no approved medical countermeasures (MCM) are available to combat MERS-CoV infections. Several neutralizing human monoclonal antibodies (mAbs), including m336, a germline-like human mAb, have been chosen as promising MCM for MERS-CoV. However, their clinical development has been hindered by the lack of a robust animal model that recapitulate the morbidity and mortality of human infections. We assessed the prophylactic and therapeutic efficacy of m336 by using well-characterized transgenic mice shown to be highly sensitive to MERS-CoV infection and disease. We found that mice treated with m336 prior to or post lethal MERS-CoV challenging were fully protected, compared to control mice which sufferered from profound weight loss and uniform death within days after infection. Taken together, these results support further development of m336 and other human monoclonal antibodies as potential therapeutics for MERS-CoV infection.
C1 [Agrawal, Anurodh Shankar; Tao, Xinrong; Garron, Tania; Algaissi, Abdullah; Tseng, Chien-Te K.] Univ Texas Med Branch, Dept Microbiol & Immunol, Galveston, TX 77555 USA.
[Ying, Tianlei] Fudan Univ, Sch Basic Med Sci, Key Lab Med Mol Virol, Minist Educ, Shanghai 200032, Peoples R China.
[Ying, Tianlei] Fudan Univ, Sch Basic Med Sci, Key Lab Med Mol Virol, Minist Hlth, Shanghai 200032, Peoples R China.
[Algaissi, Abdullah; Jiang, Shibo] Jazan Univ, Dept Med Labs Technol, Coll Appl Med Sci, Jazan, Saudi Arabia.
[Wang, Yanping; Wang, Lili; Dimitrov, Dimiter S.] NCI, Prot Interact Sect, Canc & Inflammat Program, Ctr Canc Res,NIH, Frederick, MD 21702 USA.
[Peng, Bi-Hung] Univ Texas Med Branch, Neurosci & Cell Biol, Galveston, TX 77555 USA.
RP Tseng, CTK (reprint author), Univ Texas Med Branch, Dept Microbiol & Immunol, Galveston, TX 77555 USA.
EM sktseng@utmb.edu
FU National Institutes of Health Grant [R21AI113206-01]; Center for
Biodefense and Emerging Infectious Diseases and from the Galveston
National Laboratory [5UC7AI094660-05]; University of Texas Medical
Branch, Galveston, TX; NCI; National Natural Science Foundation of China
[31570936]; T32 Biodefense Training Program by NIH [5 T32 AI 60549-12]
FX We thank Dr. Heinz Feldmann, National Institute of Health at Hamilton,
Montana, and Dr. Ron A. Fouchier, Erasmus Medical Center at Rotterdam,
The Netherlands for the MERS-CoV. This research was supported in part by
a National Institutes of Health Grant, R21AI113206-01 (to C-T.K.T), and
pilot grants from the Center for Biodefense and Emerging Infectious
Diseases and from the Galveston National Laboratory (Grant Number:
5UC7AI094660-05. Project Title: National Biocontainment Laboratories
(NBLs) Operations Support), University of Texas Medical Branch,
Galveston, TX (to C-T.K.T.), intramural funding of NCI (to DSD), and the
National Natural Science Foundation of China (#31570936 to SJ, #31570936
to TY). T.G was supported in part by a T32 Biodefense Training Program
(5 T32 AI 60549-12) awarded to UTMB by NIH.
NR 46
TC 3
Z9 3
U1 0
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 AUG 19
PY 2016
VL 6
AR 31629
DI 10.1038/srep31629
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DT7KX
UT WOS:000381666600001
PM 27538452
ER
PT J
AU Ghazizadeh, A
Griggs, W
Hikosaka, O
AF Ghazizadeh, Ali
Griggs, Whitney
Hikosaka, Okihide
TI Ecological Origins of Object Salience: Reward, Uncertainty,
Aversiveness, and Novelty
SO FRONTIERS IN NEUROSCIENCE
LA English
DT Article
DE object salience; reward; uncertainty; aversiveness; novelty
ID BASAL GANGLIA CIRCUITS; LONG-TERM-MEMORY; RECOGNITION MEMORY; DOPAMINE
NEURONS; ORBITOFRONTAL CORTEX; ATTENTIONAL CAPTURE; SIGNALS;
INFORMATION; MONKEYS; STIMULI
AB Among many objects around us, some are more salient than others (i.e., attract our attention automatically). Some objects may be inherently salient (e.g., brighter), while others may become salient by virtue of their ecological relevance through experience. However, the role of ecological experience in automatic attention has not been studied systematically. To address this question, we let subjects (macaque monkeys) view a large number of complex objects (>300), each experienced repeatedly (>5 days) with rewarding, aversive or no outcome association (mere-perceptual exposure). Test of salience was done on separate days using free viewing with no outcome. We found that gaze was biased among the objects from the outset, affecting saccades to objects or fixations within objects. When the outcome was rewarding, gaze preference was stronger (i.e., positive) for objects with larger or equal but uncertain rewards. The effects of aversive outcomes were variable. Gaze preference was positive for some outcome associations airpuff), but negative for others (e.g., time-out), possibly due to differences in threat levels. Finally, novel objects attracted gaze, but mere perceptual exposure of objects reduced their salience (learned negative salience). Our results show that, in primates, object salience is strongly influenced by previous ecological experience and is supported by a large memory capacity. Owing to such high capacity for learned salience, the ability to rapidly choose important objects can grow during the entire life to promote biological fitness.
C1 [Ghazizadeh, Ali; Griggs, Whitney; Hikosaka, Okihide] NEI, Sensorimotor Res Lab, Natl Inst Hlth Bethesda, Bldg 10, Bethesda, MD 20892 USA.
[Hikosaka, Okihide] NIDA, NIH, Baltimore, MD USA.
RP Ghazizadeh, A (reprint author), NEI, Sensorimotor Res Lab, Natl Inst Hlth Bethesda, Bldg 10, Bethesda, MD 20892 USA.
EM alieghazizadeh@gmail.com
FU Intramural Research Program at the National Institutes of Health,
National Eye Institute
FX This research was supported by the Intramural Research Program at the
National Institutes of Health, National Eye Institute. We thank H. Kim,
H. Amita, D. McMahon for valuable discussions and S. Hong for providing
technical assistance. We thank O. Dal Monte for providing the monkey
face library.
NR 69
TC 1
Z9 1
U1 9
U2 9
PU FRONTIERS MEDIA SA
PI LAUSANNE
PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015,
SWITZERLAND
SN 1662-453X
J9 FRONT NEUROSCI-SWITZ
JI Front. Neurosci.
PD AUG 19
PY 2016
VL 10
AR 378
DI 10.3389/fnins.2016.00378
PG 16
WC Neurosciences
SC Neurosciences & Neurology
GA DT9FO
UT WOS:000381801500002
PM 27594825
ER
PT J
AU Speer, SD
Pierson, TC
AF Speer, Scott D.
Pierson, Theodore C.
TI Diagnostics for Zika virus on the horizon
SO SCIENCE
LA English
DT Editorial Material
ID WEST-NILE-VIRUS; INFECTION; ANTIBODY
C1 [Speer, Scott D.; Pierson, Theodore C.] NIAID, Viral Pathogenesis Sect, Bethesda, MD 20892 USA.
RP Pierson, TC (reprint author), NIAID, Viral Pathogenesis Sect, Bethesda, MD 20892 USA.
EM piersontc@niaid.nih.gov
FU Intramural NIH HHS
NR 15
TC 2
Z9 3
U1 71
U2 84
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 AUG 19
PY 2016
VL 353
IS 6301
BP 750
EP 751
DI 10.1126/science.aah6187
PG 2
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DT5ZE
UT WOS:000381561400020
PM 27540152
ER
PT J
AU Russo, MV
McGavern, DB
AF Russo, Matthew V.
McGavern, Dorian B.
TI Inflammatory neuroprotection following traumatic brain injury
SO SCIENCE
LA English
DT Editorial Material
ID SPINAL-CORD; T-CELLS
AB Traumatic brain injury (TBI) elicits an inflammatory response in the central nervous system (CNS) that involves both resident and peripheral immune cells. Neuroinflammation can persist for years following a single TBI and may contribute to neurodegeneration. However, administration of anti-inflammatory drugs shortly after injury was not effective in the treatment of TBI patients. Some components of the neuroinflammatory response seem to play a beneficial role in the acute phase of TBI. Indeed, following CNS injury, early inflammation can set the stage for proper tissue regeneration and recovery, which can, perhaps, explain why general immunosuppression in TBI patients is disadvantageous. Here, we discuss some positive attributes of neuroinflammation and propose that inflammation be therapeutically guided in TBI patients rather than globally suppressed.
C1 [Russo, Matthew V.; McGavern, Dorian B.] NINDS, Viral Immunol & Intravital Imaging Sect, NIH, Bethesda, MD 20852 USA.
RP McGavern, DB (reprint author), NINDS, Viral Immunol & Intravital Imaging Sect, NIH, Bethesda, MD 20852 USA.
EM mcgavernd@mail.nih.gov
FU Intramural NIH HHS [, ZIA NS003112-07]
NR 15
TC 3
Z9 4
U1 14
U2 14
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 AUG 19
PY 2016
VL 353
IS 6301
BP 783
EP 785
DI 10.1126/science.aaf6260
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DT5ZE
UT WOS:000381561400036
PM 27540166
ER
PT J
AU Malecki, M
Sabo, C
Foorohar, A
Tombokan, X
AF Malecki, Marek
Sabo, Chelsea
Foorohar, Afsoon
Tombokan, Xenia
TI Novel paradigm for immunotherapy of breast cancer by engaging
prophylactic immunity against hepatitis B
SO CLINICAL AND TRANSLATIONAL MEDICINE
LA English
DT Article
DE Breast cancer; Immunotherapy; Trastuzumab; Cancer; Vaccine; HER-2;
Erb-B2; Mimotope; Hepatitis B
ID VIRUS SURFACE-ANTIGEN; MECHANISM; CELLS; IMMUNOASSAY; ANTIBODIES;
HERCEPTIN; SURVIVAL; SINGLE; YEAST
AB Background: Immunotherapy of patients suffering from the human epidermal growth factor receptor 2 overexpressing (HER-2(+)) breast cancers with the anti-HER-2 antibodies results in increase of the patients' overall survival. However, no prophylactic vaccine is available against HER-2+ breast cancers. Although, prophylactic vaccine for human hepatitis B virus (HBV) is very effective.
Specific aim: The specific aim of this work was to design, synthesize, and test bio-molecules which would engage prophylactic immunity against hepatitis B virus towards killing breast cancers cells.
Methods and Results: By biomolecular engineering, we have created a novel family of biomolecules: antibody (anti-HER-2) x vaccine (HBsAg) engineered constructs (AVEC: anti-HER-2 x HBsAg). These biomolecules were utilized for redirecting, accelerating, and amplifying of the vaccination-induced, prophylactic immunity originally targeted against HBV as therapeutic immunity, newly targeted against HER-2+ breast cancers. Treatment of the HER-2+ breast cancer cells with AVEC: anti-HER-2 x HBsAg in blood of the patients, vaccinated with HBsAg, rapidly increased efficacy of killing of HER-2+ breast cancer cells over that attained with the naked anti-HER-2 antibodies.
Conclusion: Novel antibody-vaccine engineered constructs (AVEC) facilitate redirecting, accelerating, and amplifying of prophylactic, HBV vaccination-induced immunity as immunotherapy (RAAVIIT) of HER-2+ breast cancer. We currently streamline this novel therapeutic paradigm into clinical trials of breast and other cancers.
C1 [Malecki, Marek] Phoenix Biomol Engn Fdn, San Francisco, CA 94119 USA.
[Malecki, Marek] Univ Wisconsin, Madison, WI 53706 USA.
[Malecki, Marek] NIH, Madison, WI 20892 USA.
[Sabo, Chelsea] Sutter Hlth Ctr, San Francisco, CA USA.
[Foorohar, Afsoon] Univ Sheffield, Sheffield, S Yorkshire, England.
[Tombokan, Xenia] Bruker Corp, The Woodlands, TX USA.
RP Malecki, M (reprint author), Phoenix Biomol Engn Fdn, San Francisco, CA 94119 USA.; Malecki, M (reprint author), Univ Wisconsin, Madison, WI 53706 USA.; Malecki, M (reprint author), NIH, Madison, WI 20892 USA.
EM mm@pbmef.org
FU PBMEF [2006070101]; NSF [9420056, 9522771, 9902020, 0094016]; NIH [P41
RR000570, P41 RR002301]
FX Parts of this work were supported by the funds from the PBMEF
(2006070101), the NSF (9420056, 9522771, 9902020, and 0094016), the NIH
(P41 RR000570 and P41 RR002301); to Marek Malecki MD Ph.D.-the principal
investigator. Administrators of the funding institutions had no
influence on the data acquisition and the IP.
NR 22
TC 0
Z9 0
U1 6
U2 9
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 2001-1326
J9 CLIN TRANSL MED
JI Clin. Transl. Med.
PD AUG 18
PY 2016
VL 5
AR 32
DI 10.1186/s40169-016-0111-8
PG 12
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA EH7KG
UT WOS:000391951100001
PM 27539579
ER
PT J
AU Ferre, EMN
Rose, SR
Rosenzweig, SD
Burbelo, PD
Romito, KR
Niemela, JE
Rosen, LB
Break, TJ
Gu, WJ
Hunsberger, S
Browne, SK
Hsu, AP
Rampertaap, S
Swamydas, M
Collar, AL
Kong, HH
Lee, CCR
Chascsa, D
Simcox, T
Pham, A
Bondici, A
Natarajan, M
Monsale, J
Kleiner, DE
Quezado, M
Alevizos, I
Moutsopoulos, NM
Yockey, L
Frein, C
Soldatos, A
Calvo, KR
Adjemian, J
Similuk, MN
Lang, DM
Stone, KD
Uzel, G
Kopp, JB
Bishop, RJ
Holland, SM
Olivier, KN
Fleisher, TA
Heller, T
Winer, KK
Lionakis, MS
AF Ferre, Elise M. N.
Rose, Stacey R.
Rosenzweig, Sergio D.
Burbelo, Peter D.
Romito, Kimberly R.
Niemela, Julie E.
Rosen, Lindsey B.
Break, Timothy J.
Gu, Wenjuan
Hunsberger, Sally
Browne, Sarah K.
Hsu, Amy P.
Rampertaap, Shakuntala
Swamydas, Muthulekha
Collar, Amanda L.
Kong, Heidi H.
Lee, Chyi-Chia Richard
Chascsa, David
Simcox, Thomas
Pham, Angela
Bondici, Anamaria
Natarajan, Mukil
Monsale, Joseph
Kleiner, David E.
Quezado, Martha
Alevizos, Ilias
Moutsopoulos, Niki M.
Yockey, Lynne
Frein, Cathleen
Soldatos, Ariane
Calvo, Katherine R.
Adjemian, Jennifer
Similuk, Morgan N.
Lang, David M.
Stone, Kelly D.
Uzel, Gulbu
Kopp, Jeffrey B.
Bishop, Rachel J.
Holland, Steven M.
Olivier, Kenneth N.
Fleisher, Thomas A.
Heller, Theo
Winer, Karen K.
Lionakis, Michail S.
TI Redefined clinical features and diagnostic criteria in autoimmune
polyendocrinopathy-candidiasis-ectodermal dystrophy
SO JCI INSIGHT
LA English
DT Article
ID SYNDROME TYPE-I; CHRONIC MUCOCUTANEOUS CANDIDIASIS; COMMON VARIABLE
IMMUNODEFICIENCY; POLYGLANDULAR SYNDROME TYPE-1; B-CELL POPULATION;
ADDISONS-DISEASE; REGULATOR GENE; PERIPHERAL-BLOOD; APS-I;
AUTOANTIBODIES
AB Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a rare primary immunodeficiency disorder typically caused by homozygous AIRE mutations. It classically presents with chronic mucocutaneous candidiasis and autoimmunity that primarily targets endocrine tissues; hypoparathyroidism and adrenal insufficiency are most common. Developing any two of these classic triad manifestations establishes the diagnosis. Although widely recognized in Europe, where nonendocrine autoimmune manifestations are uncommon, APECED is less defined in patients from the Western Hemisphere. We enrolled 35 consecutive American APECED patients (33 from the US) in a prospective observational natural history study and systematically examined their genetic, clinical, autoantibody, and immunological characteristics. Most patients were compound heterozygous; the most common AIRE mutation was c.967_979del13. All but one patient had anti-IFN-omega autoantibodies, including 4 of 5 patients without biallelic AIRE mutations. Urticarial eruption, hepatitis, gastritis, intestinal dysfunction, pneumonitis, and Sjogren's-like syndrome, uncommon entities in European APECED cohorts, affected 40%-80% of American cases. Development of a classic diagnostic dyad was delayed at mean 7.38 years. Eighty percent of patients developed a median of 3 non-triad manifestations before a diagnostic dyad. Only 20% of patients had their first two manifestations among the classic triad. Urticarial eruption, intestinal dysfunction, and enamel hypoplasia were prominent among early manifestations. Patients exhibited expanded peripheral CD4(+) T cells and CD21(lo)CD38(lo) B lymphocytes. In summary, American APECED patients develop a diverse syndrome, with dramatic enrichment in organ-specific nonendocrine manifestations starting early in life, compared with European patients. Incorporation of these new manifestations into American diagnostic criteria would accelerate diagnosis by approximately 4 years and potentially prevent life-threatening endocrine complications.
C1 [Ferre, Elise M. N.; Rose, Stacey R.; Break, Timothy J.; Swamydas, Muthulekha; Collar, Amanda L.; Pham, Angela; Bondici, Anamaria; Natarajan, Mukil; Yockey, Lynne; Lionakis, Michail S.] NIAID, Fungal Pathogenesis Unit, Lab Clin Infect Dis, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Rosenzweig, Sergio D.; Romito, Kimberly R.; Niemela, Julie E.; Rampertaap, Shakuntala; Monsale, Joseph; Fleisher, Thomas A.] NIH, Serv Immunol, Dept Lab Med, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA.
[Burbelo, Peter D.] Natl Inst Dent & Craniofacial Res, Dent Clin Res Core, Bethesda, MD USA.
[Rosen, Lindsey B.; Browne, Sarah K.; Hsu, Amy P.; Yockey, Lynne; Uzel, Gulbu; Holland, Steven M.] NIAID, Immunopathogenesis Sect, Lab Clin Infect Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Gu, Wenjuan; Frein, Cathleen] Natl Canc Inst NCI Campus Frederick, Clin Res Directorate, Clin Monitoring Res Program, Leidos Biomed Res Inc, Frederick, MD USA.
[Hunsberger, Sally] NIAID, Biostat Res Branch, Div Clin Res, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Kong, Heidi H.; Kleiner, David E.; Quezado, Martha] NCI, Dermatol Branch, Ctr Canc Res, Bldg 10, Bethesda, MD 20892 USA.
[Lee, Chyi-Chia Richard] NCI, Pathol Lab, Ctr Canc Res, Bldg 10, Bethesda, MD 20892 USA.
[Chascsa, David; Simcox, Thomas; Heller, Theo] NIDDK, Translat Hepatol Unit, Liver Dis Branch, Bethesda, MD 20892 USA.
[Alevizos, Ilias] Natl Inst Dent & Craniofacial Res, Sjogrens Syndrome & Salivary Gland Dysfunct Unit, NIH, Bethesda, MD USA.
[Moutsopoulos, Niki M.] Natl Inst Dent & Craniofacial Res, Oral Immun & Inflammat Unit, NIH, Bethesda, MD USA.
[Soldatos, Ariane] NIH, Undiag Dis Program, Common Fund, Off Director, Bldg 10, Bethesda, MD 20892 USA.
[Soldatos, Ariane] NHGRI, Bethesda, MD 20892 USA.
[Calvo, Katherine R.] NIH, Hematol Sect, Dept Lab Med, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA.
[Adjemian, Jennifer] NIAID, Epidemiol Unit, Lab Clin Infect Dis, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Similuk, Morgan N.] NIAID, Immunol Lab, Bldg 10, Bethesda, MD 20892 USA.
[Lang, David M.] NIH, Pediat Consult Serv, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA.
[Stone, Kelly D.] NIAID, Lab Allerg Dis, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Kopp, Jeffrey B.] NIDDK, Kidney Dis Branch, Bethesda, MD 20892 USA.
[Bishop, Rachel J.] NEI, Consult Serv Sect, Bethesda, MD 20892 USA.
[Olivier, Kenneth N.] NHLBI, Cardiovasc & Pulm Branch, Bldg 10, Bethesda, MD 20892 USA.
[Winer, Karen K.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pediat Growth & Nutr Branch, NIH, Bethesda, MD USA.
[Rose, Stacey R.] Baylor Coll Med, Div Infect Dis, Houston, TX 77030 USA.
[Browne, Sarah K.] US FDA, Div Vaccines & Related Prod Applicat, Ctr Biol Evaluat & Res, Silver Spring, MD USA.
RP Lionakis, MS (reprint author), NIAID, Fungal Pathogenesis Unit, LCID, NIH, 9000 Rockville Pike,Bldg 10,Room 11C102, Bethesda, MD 20892 USA.
EM lionakism@mail.nih.gov
NR 63
TC 0
Z9 0
U1 1
U2 1
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 AUG 18
PY 2016
VL 1
IS 13
DI 10.1172/jci.insight.88782
PG 18
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA EB1NO
UT WOS:000387119700010
ER
PT J
AU Johnson, AD
AF Johnson, Andrew D.
TI Pairing megakaryopoiesis methylation with PEAR1
SO BLOOD
LA English
DT Editorial Material
ID PLATELET AGGREGABILITY; AGGREGATION; ACTIVATION; VARIANT; GENE
C1 [Johnson, Andrew D.] NHLBI, Bldg 10, Bethesda, MD 20892 USA.
RP Johnson, AD (reprint author), NHLBI, Bldg 10, Bethesda, MD 20892 USA.
NR 10
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 AUG 18
PY 2016
VL 128
IS 7
BP 890
EP 892
DI 10.1182/blood-2016-06-723940
PG 5
WC Hematology
SC Hematology
GA DW7ML
UT WOS:000383834800006
PM 27539998
ER
PT J
AU Lama, JR
Karuna, ST
Grant, SP
Swann, EM
Ganoza, C
Segura, P
Montano, SM
Lacherre, M
De Rosa, SC
Buchbinder, S
Sanchez, J
McElrath, MJ
Lemos, MP
AF Lama, Javier R.
Karuna, Shelly T.
Grant, Shannon P.
Swann, Edith M.
Ganoza, Carmela
Segura, Patricia
Montano, Silvia M.
Lacherre, Martin
De Rosa, Stephen C.
Buchbinder, Susan
Sanchez, Jorge
McElrath, M. Juliana
Lemos, Maria P.
CA HVTN 914 Study Team
TI Transient Peripheral Immune Activation follows Elective Sigmoidoscopy or
Circumcision in a Cohort Study of MSM at Risk of HIV Infection
SO PLOS ONE
LA English
DT Article
ID T-CELL RESPONSES; VIRUS-INFECTION; MEN; SEX; VACCINE; TRIAL;
ACQUISITION; PREVENTION; SAFETY; PERU
AB Background
Rectal and genital sampling in HIV prevention trials permits assessments at the site of HIV entry. Yet the safety and acceptability of circumcision and sigmoidoscopy (and associated abstinence recommendations) are unknown in uncircumcised men who have sex with men (MSM) at high risk of HIV infection.
Methods
Twenty-nine HIV-seronegative high-risk Peruvian MSM agreed to elective sigmoidoscopy biopsy collections (weeks 2 and 27) and circumcision (week 4) in a 28-week cohort study designed to mimic an HIV vaccine study mucosal collection protocol. We monitored adherence to abstinence recommendations, procedure-related complications, HIV infections, peripheral immune activation, and retention.
Results
Twenty-three (79.3%) underwent a first sigmoidoscopy, 21 (72.4%) were circumcised, and 16 (55.2%) completed a second sigmoidoscopy during the study period. All who underwent procedures completed the associated follow-up safety visits. Those completing the procedures reported they were well tolerated, and complication rates were similar to those reported in the literature. Immune activation was detected during the healing period (1 week post-sigmoidoscopy, 6 weeks post-circumcision), including increases in CCR5(+)CD4(+)T cells and alpha 4 beta 7(+)CD4(+)T cells. Most participants adhered to post-circumcision abstinence recommendations whereas reduced adherence occurred post-sigmoidoscopy.
Conclusion
Rectosigmoid mucosal and genital tissue collections were safe in high-risk MSM. Although the clinical implications of the post-procedure increase in peripheral immune activation markers are unknown, they reinforce the need to provide ongoing risk reduction counseling and support for post-procedure abstinence recommendations. Future HIV vaccine studies should also consider the effects of mucosal and tissue collections on peripheral blood endpoints in trial design and analysis.
C1 [Lama, Javier R.; Ganoza, Carmela; Segura, Patricia; Lacherre, Martin; Sanchez, Jorge] Asociac Civil Impacta Salud & Educ, Lima, Peru.
[Karuna, Shelly T.; Grant, Shannon P.; De Rosa, Stephen C.; McElrath, M. Juliana; Lemos, Maria P.] Fred Hutchinson Canc Res Ctr, Vaccine & Infect Dis Div, 1124 Columbia St, Seattle, WA 98104 USA.
[Swann, Edith M.] NIAID, Vaccine Clin Res Branch, Div AIDS, US NIH, Bethesda, MD USA.
[Montano, Silvia M.] US Naval Med Res Unit 6, Callao, Peru.
[De Rosa, Stephen C.; Sanchez, Jorge] Univ Washington, Dept Global Hlth, Seattle, WA 98195 USA.
[McElrath, M. Juliana] Univ Washington, Dept Lab Med, Seattle, WA 98195 USA.
[McElrath, M. Juliana] Univ Washington, Dept Med, Seattle, WA USA.
[Buchbinder, Susan] San Francisco Dept Hlth, San Francisco, CA USA.
RP Lemos, MP (reprint author), Fred Hutchinson Canc Res Ctr, Vaccine & Infect Dis Div, 1124 Columbia St, Seattle, WA 98104 USA.
EM mlemos@fredhutch.org
FU National Institute of Allergy and Infectious Diseases of the National
Institutes of Health [UM1AI068614, UM1AI068618, UM1AI068635,
UM1AI069438]; National Institute of Allergy and Infectious Diseases of
the U.S. National Institutes of Health
FX Research reported in this publication was supported by the National
Institute of Allergy and Infectious Diseases of the National Institutes
of Health under award numbers UM1AI068614, UM1AI068618, UM1AI068635, and
UM1AI069438. The content is the responsibility of the authors and does
not necessarily represent the official views, policy or position of the
U.S. National Institutes of Health, Department of the Navy, Department
of Defense, or U.S. Government. Silvia Montano and Edith Swann are
employees of the U.S. Government, who contributed to this work as part
of their official duties. No copyright protection is available for their
work as defined by Title 17 U.S.C. 105 and 101.; Research reported in
this publication was supported by the National Institute of Allergy and
Infectious Diseases of the U.S. National Institutes of Health. The
content is the responsibility of the authors and does not necessarily
represent the official views, policy or position of the U.S. National
Institutes of Health, the Department of the Navy, the Department of
Defense, or the U.S. Government. Silvia Montano and Edith Swann are
employees of the U.S. Government who contributed to this work as part of
her official duties. No copyright protection is available for their work
as defined by Titles 17 U.S.C. 105 and 101.
NR 47
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 AUG 18
PY 2016
VL 11
IS 8
AR e0160487
DI 10.1371/journal.pone.0160487
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DT6ES
UT WOS:000381577000022
PM 27536938
ER
PT J
AU Sathyanarayana, BK
Li, P
Lin, JX
Leonard, WJ
Lee, B
AF Sathyanarayana, Bangalore K.
Li, Peng
Lin, Jian-Xin
Leonard, Warren J.
Lee, Byungkook
TI Molecular Models of STAT5A Tetramers Complexed to DNA Predict Relative
GenomeWide Frequencies of the Spacing between the Two Dimer Binding
Motifs of the Tetramer Binding Sites
SO PLOS ONE
LA English
DT Article
ID TRANSACTIVATION DOMAINS; GENE; TRANSCRIPTION; RECRUITMENT; ACTIVATION;
INDUCTION; GROWTH; CELLS
AB STAT proteins bind DNA as dimers and tetramers to control cellular development, differentiation, survival, and expansion. The tetramer binding sites are comprised of two dimer-binding sites repeated in tandem. The genome-wide distribution of the spacings between the dimer binding sites shows a distinctive, non-random pattern. Here, we report on estimating the feasibility of building possible molecular models of STAT5A tetramers bound to a DNA double helix with all possible spacings between the dimer binding sites. We found that the calculated feasibility estimates correlated well with the experimentally measured frequency of tetramer-binding sites. This suggests that the feasibility of forming the tetramer complex was a major factor in the evolution of this DNA sequence variation.
C1 [Sathyanarayana, Bangalore K.; Lee, Byungkook] NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Li, Peng; Lin, Jian-Xin; Leonard, Warren J.] NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA.
[Li, Peng; Lin, Jian-Xin; Leonard, Warren J.] NHLBI, Ctr Immunol, NIH, Bethesda, MD 20892 USA.
RP Lee, B (reprint author), NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.; Leonard, WJ (reprint author), NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA.; Leonard, WJ (reprint author), NHLBI, Ctr Immunol, NIH, Bethesda, MD 20892 USA.
EM leonardw@nhlbi.nih.gov; BKLee@mail.nih.gov
OI Lee, Byungkook/0000-0002-3339-4582
FU Intramural Research Program of the NIH; National Cancer Institute;
Center for Cancer Research; Division of Intramural Research, National
Heart, Lung, and Blood Institute; National Institutes of Health
(National Center for Research Resources) [2P41RR001081]; National
Institutes of Health (National Institute of General Medical Sciences)
[9P41GM103311]
FX This research was supported by the Intramural Research Program of the
NIH, National Cancer Institute, Center for Cancer Research and the
Division of Intramural Research, National Heart, Lung, and Blood
Institute. The Chimera software we used was developed by the Resource
for Biocomputing, Visualization, and Informatics at the University of
California, San Francisco, with support from the National Institutes of
Health (National Center for Research Resources grant 2P41RR001081,
National Institute of General Medical Sciences grant 9P41GM103311). The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 24
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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 AUG 18
PY 2016
VL 11
IS 8
AR e0160339
DI 10.1371/journal.pone.0160339
PG 21
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DT6ES
UT WOS:000381577000017
PM 27537504
ER
PT J
AU Shukla, A
Yang, YH
Madanikia, S
Ho, Y
Li, MM
Sanchez, V
Cataisson, C
Huang, J
Yuspa, SH
AF Shukla, Anjali
Yang, Yihan
Madanikia, Sara
Ho, Yan
Li, Mangmang
Sanchez, Vanesa
Cataisson, Christophe
Huang, Jing
Yuspa, Stuart H.
TI Elevating CLIC4 in Multiple Cell Types Reveals a TGF-Dependent Induction
of a Dominant Negative Smad7 Splice Variant
SO PLOS ONE
LA English
DT Article
ID BETA SUPERFAMILY; SKIN CARCINOGENESIS; TUMOR-SUPPRESSOR; GROWTH;
INHIBITION; PROLIFERATION; KERATINOCYTES; NUCLEUS; DISEASE; CANCER
AB CLIC4 (Chloride intracellular channel 4) belongs to a family of putative intracellular chloride channel proteins expressed ubiquitously in multiple tissues. CLIC4 is predominantly soluble and traffics between the cytoplasm and nucleus and participates in cell cycle control and differentiation. Transforming growth factor beta (TGF-beta) elevates CLIC4, which enhances TGF-beta signaling through CLIC4 mediated stabilization of phospho-Smad2/3. CLIC4 is essential for TGF-beta induced conversion of fibroblasts to myofibroblasts and expression of matrix proteins, signaling via the p38MAPK pathway. Therefore, regulation of TGF-beta signaling is a major mechanism by which CLIC4 modifies normal growth and differentiation. We now report that elevated CLIC4 alters Smad7 function, a feedback inhibitor of the TGF-beta pathway. Overexpression of CLIC4 in keratinocytes, mouse embryonic fibroblasts and other mouse and human cell types increases the expression of Smad7 Delta, a novel truncated form of Smad7. The alternatively spliced Smad7 Delta variant is missing 94bp in exon 4 of Smad 7 and is conserved between mouse and human cells. The deletion is predicted to lack the TGF-beta signaling inhibitory MH2 domain of Smad7. Treatment with exogenous TGF-beta 1 also enhances expression of Smad7 Delta that is amplified in the presence of CLIC4. While Smad7 expression inhibits TGF-beta signaling, exogenously expressed Smad7 Delta does not inhibit TGF-beta signaling as determined by TGF-beta dependent proliferation, reporter assays and phosphorylation of Smad proteins. Instead, exogenous Smad7 Delta acts as a dominant negative inhibitor of Smad7, thus increasing TGF-beta signaling. This discovery adds another dimension to the myriad ways by which CLIC4 modifies TGF-beta signaling.
C1 [Shukla, Anjali; Yang, Yihan; Madanikia, Sara; Ho, Yan; Li, Mangmang; Sanchez, Vanesa; Cataisson, Christophe; Huang, Jing; Yuspa, Stuart H.] NCI, Lab Canc Biol & Genet, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Yuspa, SH (reprint author), NCI, Lab Canc Biol & Genet, Ctr Canc Res, Bethesda, MD 20892 USA.
EM yuspas@mail.nih.gov
FU NCI, CCR intramural program [BC005445-30]
FX This work was conducted with funding to SHY from the NCI, CCR intramural
program under project BC005445-30.
NR 36
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 AUG 18
PY 2016
VL 11
IS 8
AR e0161410
DI 10.1371/journal.pone.0161410
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DT6ES
UT WOS:000381577000102
PM 27536941
ER
PT J
AU Silson, EH
Steel, AD
Baker, CI
AF Silson, Edward H.
Steel, Adam D.
Baker, Chris I.
TI Scene-Selectivity and Retinotopy in Medial Parietal Cortex
SO FRONTIERS IN HUMAN NEUROSCIENCE
LA English
DT Article
DE retinotopy; population receptive fields; scene-selectivity;
resting-state functional connectivity; memory
ID HUMAN RETROSPLENIAL CORTEX; BOLD-CONTRAST SENSITIVITY; LATERAL OCCIPITAL
CORTEX; HUMAN VISUAL-CORTEX; OCCIPITOTEMPORAL CORTEX; PLACE AREA; FMRI;
PARAHIPPOCAMPAL; CONNECTIVITY; REGIONS
AB Functional imaging studies in human reliably identify a trio of scene-selective regions, one on each of the lateral [occipital place area (OPA)], ventral [parahippocampal place area (PPA)], and medial [retrosplenial complex (RSC)] cortical surfaces. Recently, we demonstrated differential retinotopic biases for the contralateral lower and upper visual fields within OPA and PPA, respectively. Here, using functional magnetic resonance imaging, we combine detailed mapping of both population receptive fields (pRF) and category-selectivity, with independently acquired resting-state functional connectivity analyses, to examine scene and retinotopic processing within medial parietal cortex. We identified a medial scene-selective region, which was contained largely within the posterior and ventral bank of the parieto-occipital sulcus (POS). While this region is typically referred to as RSC, the spatial extent of our scene-selective region typically did not extend into retrosplenial cortex, and thus we adopt the term medial place area (MPA) to refer to this visually defined scene-selective region. Intriguingly MPA co-localized with a region identified solely on the basis of retinotopic sensitivity using pRF analyses. We found that MPA demonstrates a significant contralateral visual field bias, coupled with large pRF sizes. Unlike OPA and PPA. MPA did not show a consistent bias to a single visual quadrant. MPA also co-localized with a region identified by strong differential functional connectivity with PPA and the human face-selective fusiform face area (FFA), commensurate with its functional selectivity. Functional connectivity with OPA was much weaker than with PPA, and similar to that with face-selective occipital face area (OFA), suggesting a closer link with ventral than lateral cortex. Consistent with prior research, we also observed differential functional connectivity in medial parietal cortex for anterior over posterior PPA, as well as a region on the lateral surface, the caudal inferior parietal lobule (cIPL). However, the differential connectivity in medial parietal cortex was found principally anterior of MPA. We suggest that there is posterior anterior gradient within medial parietal cortex, with posterior regions in the POS showing retinotopically based scene-selectivity and more anterior regions showing connectivity that may be more reflective of abstract, navigationally pertinent and possibly mnemonic representations.
C1 [Silson, Edward H.; Steel, Adam D.; Baker, Chris I.] NIMH, Lab Brain & Cognit, Bethesda, MD 20892 USA.
[Steel, Adam D.] Univ Oxford, John Radcliffe Hosp, Physiol Neuroimaging Grp, FMRIB Ctr, Oxford, England.
RP Silson, EH (reprint author), NIMH, Lab Brain & Cognit, Bethesda, MD 20892 USA.
EM ed.silson@nih.gov
OI Steel, Adam/0000-0001-8876-933X
FU Intramural Research Program of the National Institutes of Health -
National Institute of Mental Health Clinical Study Protocol
[ZIAMH002909, 93-M-0170, NCT00001360]
FX This work was supported by the Intramural Research Program (ZIAMH002909)
of the National Institutes of Health - National Institute of Mental
Health Clinical Study Protocol 93-M-0170, NCT00001360.
NR 54
TC 3
Z9 3
U1 5
U2 5
PU FRONTIERS MEDIA SA
PI LAUSANNE
PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015,
SWITZERLAND
SN 1662-5161
J9 FRONT HUM NEUROSCI
JI Front. Hum. Neurosci.
PD AUG 18
PY 2016
VL 10
AR 412
DI 10.3389/fnhum.2016.00412
PG 17
WC Neurosciences; Psychology
SC Neurosciences & Neurology; Psychology
GA DT6LR
UT WOS:000381596200001
PM 27588001
ER
PT J
AU Reichert, MC
Brown, HE
Evans, TA
AF Reichert, Marie C.
Brown, Haley E.
Evans, Timothy A.
TI In vivo functional analysis of Drosophila Robo1 immunoglobulin-like
domains
SO NEURAL DEVELOPMENT
LA English
DT Article
DE Drosophila; Slit; Robo; Axon guidance; Midline crossing;
Immunoglobulin-like domain
ID COMMISSURAL AXON GUIDANCE; GROWTH CONE GUIDANCE; CNS MIDLINE; ROUNDABOUT
RECEPTOR; DISTINCT ROLES; SLIT BINDING; REPULSION; EXPRESSION; NEURONS;
SYSTEM
AB Background: In animals with bilateral symmetry, midline crossing of axons in the developing central nervous system is regulated by Slit ligands and their neuronal Roundabout (Robo) receptors. Multiple structural domains are present in an evolutionarily conserved arrangement in Robo family proteins, but our understanding of the functional importance of individual domains for midline repulsive signaling is limited.
Methods: We have examined the functional importance of each of the five conserved immunoglobulin-like (Ig) domains within the Drosophila Robo1 receptor. We generated a series of Robo1 variants, each lacking one of the five Ig domains (Ig1-5), and tested each for their ability to bind Slit when expressed in cultured Drosophila cells. We used a transgenic approach to express each variant in robo1's normal expression pattern in wild-type and robo1 mutant embryos, and examined the effects of deleting each domain on receptor expression, axonal localization, regulation, and midline repulsive signaling in vivo.
Results: We show that individual deletion of Ig domains 2-5 does not interfere with Robo1's ability to bind Slit, while deletion of Ig1 strongly disrupts Slit binding. None of the five Ig domains (Ig1-5) are individually required for proper expression of Robo1 in embryonic neurons, for exclusion from commissural axon segments in wild-type embryos, or for downregulation by Commissureless (Comm), a negative regulator of Slit-Robo repulsion in Drosophila. Each of the Robo1 Ig deletion variants (with the exception of Robo1 Delta Ig1) were able to restore midline crossing in robo1 mutant embryos to nearly the same extent as full-length Robo1, indicating that Ig domains 2-5 are individually dispensable for midline repulsive signaling in vivo.
Conclusions: Our findings indicate that four of the five Ig domains within Drosophila Robo1 are dispensable for its role in midline repulsion, despite their strong evolutionary conservation, and highlight a unique requirement for the Slit-binding Ig1 domain in the regulation of midline crossing.
C1 [Reichert, Marie C.; Brown, Haley E.; Evans, Timothy A.] Univ Arkansas, Dept Biol Sci, Fayetteville, AR 72701 USA.
[Reichert, Marie C.] NHGRI, Intramural Res Training Program, Bethesda, MD 20892 USA.
RP Evans, TA (reprint author), Univ Arkansas, Dept Biol Sci, Fayetteville, AR 72701 USA.
EM evanst@uark.edu
OI Evans, Timothy/0000-0002-2756-8064
FU University of Arkansas
FX This work was supported by funds from the University of Arkansas. The
funders had no role in the design of the study, collection, analysis,
and interpretation of data, decision to publish, or preparation of the
manuscript.
NR 57
TC 0
Z9 0
U1 5
U2 5
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1749-8104
J9 NEURAL DEV
JI Neural Dev.
PD AUG 18
PY 2016
VL 11
AR 15
DI 10.1186/s13064-016-0071-0
PG 11
WC Developmental Biology; Neurosciences
SC Developmental Biology; Neurosciences & Neurology
GA DU9EV
UT WOS:000382520000001
PM 27539083
ER
PT J
AU Sato, K
Sato, N
Xu, BY
Nakamura, Y
Nagaya, T
Choyke, PL
Hasegawa, Y
Kobayashi, H
AF Sato, Kazuhide
Sato, Noriko
Xu, Biying
Nakamura, Yuko
Nagaya, Tadanobu
Choyke, Peter L.
Hasegawa, Yoshinori
Kobayashi, Hisataka
TI Spatially selective depletion of tumor-associated regulatory T cells
with near-infrared photoimmunotherapy
SO SCIENCE TRANSLATIONAL MEDICINE
LA English
DT Article
ID IMMUNE CHECKPOINT BLOCKADE; CANCER-IMMUNOTHERAPY; IN-VIVO; REJECTION;
IMMUNOLOGY; METASTASES; MECHANISM; RECEPTOR; THERAPY; GROWTH
AB Current immunotherapies for cancer seek to modulate the balance among different immune cell populations, thereby promoting antitumor immune responses. However, because these are systemic therapies, they often cause treatment-limiting autoimmune adverse effects. It would be ideal to manipulate the balance between suppressor and effector cells within the tumor without disturbing homeostasis elsewhere in the body. CD4(+)CD25(+)Foxp3(+) regulatory T cells (T-regs) are well-known immunosuppressor cells that play a key role in tumor immunoevasion and have been the target of systemic immunotherapies. We used CD25-targeted near-infrared photoimmunotherapy (NIR-PIT) to selectively deplete T-regs, thus activating CD8 T and natural killer cells and restoring local antitumor immunity. This not only resulted in regression of the treated tumor but also induced responses in separate untreated tumors of the same cell line derivation. We conclude that CD25-targeted NIR-PIT causes spatially selective depletion of T-regs, thereby providing an alternative approach to cancer immunotherapy.
C1 [Sato, Kazuhide; Sato, Noriko; Nakamura, Yuko; Nagaya, Tadanobu; Choyke, Peter L.; Kobayashi, Hisataka] NCI, Mol Imaging Program, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Sato, Kazuhide; Hasegawa, Yoshinori] Nagoya Univ, Grad Sch Med, Dept Resp Med, Nagoya, Aichi 4668550, Japan.
[Xu, Biying] NHLBI, Image Probe Dev Ctr, NIH, Bldg 10, Bethesda, MD 20892 USA.
RP Kobayashi, H (reprint author), NCI, Mol Imaging Program, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM kobayash@mail.nih.gov
FU Intramural Research Program of the NIH, National Cancer Institute,
Center for Cancer Research
FX This research was supported by the Intramural Research Program of the
NIH, National Cancer Institute, Center for Cancer Research.
NR 43
TC 1
Z9 1
U1 6
U2 6
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 AUG 17
PY 2016
VL 8
IS 352
AR 352ra110
DI 10.1126/scitranslmed.aaf6843
PG 12
WC Cell Biology; Medicine, Research & Experimental
SC Cell Biology; Research & Experimental Medicine
GA DW9WP
UT WOS:000384013700004
ER
PT J
AU Saethang, T
Payne, DM
Avihingsanon, Y
Pisitkun, T
AF Saethang, Thammakorn
Payne, D. Michael
Avihingsanon, Yingyos
Pisitkun, Trairak
TI A machine learning strategy for predicting localization of
post-translational modification sites in protein-protein interacting
regions
SO BMC BIOINFORMATICS
LA English
DT Article
DE Post-translational modification; Protein-protein interacting region;
Machine learning; AAindex
ID PAIRWISE CONTACT POTENTIALS; DATA SETS; PHOSPHORYLATION; BINDING;
CLASSIFICATION; RESOURCE; GLYCOSYLATION; DATABASE
AB Background: One very important functional domain of proteins is the protein-protein interacting region (PPIR), which forms the binding interface between interacting polypeptide chains. Post-translational modifications (PTMs) that occur in the PPIR can either interfere with or facilitate the interaction between proteins. The ability to predict whether sites of protein modifications are inside or outside of PPIRs would be useful in further elucidating the regulatory mechanisms by which modifications of specific proteins regulate their cellular functions.
Results: Using two of the comprehensive databases for protein-protein interaction and protein modification site data (PDB and PhosphoSitePlus, respectively), we created new databases that map PTMs to their locations inside or outside of PPIRs. The mapped PTMs represented only 5 % of all known PTMs. Thus, in order to predict localization within or outside of PPIRs for the vast majority of PTMs, a machine learning strategy was used to generate predictive models from these mapped databases. For the three mapped PTM databases which had sufficient numbers of modification sites for generating models (acetylation, phosphorylation, and ubiquitylation), the resulting models yielded high overall predictive performance as judged by a combined performance score (CPS). Among the multiple properties of amino acids that were used in the classification tasks, hydrophobicity was found to contribute substantially to the performance of the final predictive models. Compared to the other classifiers we also evaluated, the SVM provided the best performance overall.
Conclusions: These models are the first to predict whether PTMs are located inside or outside of PPIRs, as demonstrated by their high predictive performance. The models and data presented here should be useful in prioritizing both known and newly identified PTMs for further studies to determine the functional relationship between specific PTMs and protein-protein interactions. The implemented R package is available online (http://sysbio.chula.ac.th/PtmPPIR).
C1 [Saethang, Thammakorn; Payne, D. Michael; Pisitkun, Trairak] Chulalongkorn Univ, Syst Biol Ctr, Res Affairs, Fac Med, 1873 Rama 4 Rd, Bangkok 10330, Thailand.
[Avihingsanon, Yingyos] Chulalongkorn Univ, Div Nephrol, Dept Med, Fac Med, 1873 Rama 4 Rd, Bangkok 10330, Thailand.
[Pisitkun, Trairak] NHLBI, Epithelial Syst Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Pisitkun, T (reprint author), Chulalongkorn Univ, Syst Biol Ctr, Res Affairs, Fac Med, 1873 Rama 4 Rd, Bangkok 10330, Thailand.; Avihingsanon, Y (reprint author), Chulalongkorn Univ, Div Nephrol, Dept Med, Fac Med, 1873 Rama 4 Rd, Bangkok 10330, Thailand.; Pisitkun, T (reprint author), NHLBI, Epithelial Syst Biol Lab, NIH, Bethesda, MD 20892 USA.
EM fmedyah@md.chula.ac.th; pisitkut@nhlbi.nih.gov
OI Pisitkun, Trairak/0000-0001-6677-2271
FU Chulalongkorn Academic Advancement into Its 2nd Century Project
(CUAASC); Grants for Development of New Faculty Staff
Ratchadaphiseksomphot Endowment Fund; Post-Doctoral Scholarship,
Chulalongkorn University Ratchadaphiseksomphot Fund
FX This work was supported by the Chulalongkorn Academic Advancement into
Its 2nd Century Project (CUAASC) (TP), and the Grants for Development of
New Faculty Staff Ratchadaphiseksomphot Endowment Fund (TS). TS was also
supported by Post-Doctoral Scholarship, Chulalongkorn University
Ratchadaphiseksomphot Fund.
NR 54
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 1471-2105
J9 BMC BIOINFORMATICS
JI BMC Bioinformatics
PD AUG 17
PY 2016
VL 17
AR 307
DI 10.1186/s12859-016-1165-8
PG 15
WC Biochemical Research Methods; Biotechnology & Applied Microbiology;
Mathematical & Computational Biology
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Mathematical & Computational Biology
GA DV3NR
UT WOS:000382829900002
PM 27534850
ER
PT J
AU Funk, D
Coen, K
Tamadon, S
Hope, BT
Shaham, Y
Le, AD
AF Funk, Douglas
Coen, Kathleen
Tamadon, Sahar
Hope, Bruce T.
Shaham, Yavin
Le, A. D.
TI Role of Central Amygdala Neuronal Ensembles in Incubation of Nicotine
Craving
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
DE central amygdala; Daun02; Fos; incubation of craving; nicotine;
orbitofrontal cortex
ID ADULT MALE RATS; MEDIAL PREFRONTAL CORTEX; TIME-DEPENDENT CHANGES;
PROTEIN-KINASE-A; NUCLEUS-ACCUMBENS; DRUG RELAPSE; COCAINE-SEEKING;
INDUCED REINSTATEMENT; SMOKING-CESSATION; SIGNALING PATHWAY
AB The craving response to smoking-associated cues in humans or to intravenous nicotine-associated cues in adult rats progressively increases or incubates after withdrawal. Here, we further characterized incubation of nicotine craving in the rat model by determining whether this incubation is observed after adolescent-onset nicotine self-administration. We also used the neuronal activity marker Fos and the Daun02 chemogenetic inactivation procedure to identify cue-activated neuronal ensembles that mediate incubation of nicotine craving. Wetrained adolescent and adult male rats to self-administer nicotine (2 h/d for 12 d) and assessed cue-induced nicotine seeking in extinction tests (1 h) after 1, 7, 14, or 28 withdrawal days. In both adult and adolescent rats, nicotine seeking in the relapse tests followed an inverted U-shaped curve, with maximal responding on withdrawal day 14. Independent of the withdrawal day, nicotine seeking in the relapse tests was higher in adult than in adolescent rats. Analysis of Fos expression in different brain areas of adolescent and adult rats on withdrawal days 1 and 14 showed time-dependent increases in the number of Fos-positive neurons in central and basolateral amygdala, orbitofrontal cortex, ventral and dorsal medial prefrontal cortex, and nucleus accumbens core and shell. In adult Fos-lacZ transgenic rats, selective inactivation of nicotine-cue-activated Fos neurons in central amygdala, but not orbitofrontal cortex, decreased "incubated" nicotine seeking on withdrawal day 14. Our results demonstrate that incubation of nicotine craving occurs after adolescent-onset nicotine self-administration and that neuronal ensembles in central amygdala play a critical role in this incubation.
C1 [Funk, Douglas; Coen, Kathleen; Tamadon, Sahar; Le, A. D.] Ctr Addict & Mental Hlth, Campbell Family Mental Hlth Res Inst, Neurobiol Alcohol Lab, 33 Russell St, Toronto, ON M5S 2S1, Canada.
[Le, A. D.] Univ Toronto, Dept Pharmacol & Toxicol, Toronto, ON M5S 1A8, Canada.
[Le, A. D.] Univ Toronto, Dept Psychiat, Toronto, ON M5S 1A8, Canada.
[Hope, Bruce T.; Shaham, Yavin] NIDA, Behav Neurosci Branch, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
RP Funk, D (reprint author), Ctr Addict & Mental Hlth, Campbell Family Mental Hlth Res Inst, Neurobiol Alcohol Lab, 33 Russell St, Toronto, ON M5S 2S1, Canada.
EM Douglas.Funk@camh.ca
RI Hope, Bruce/A-9223-2010
OI Hope, Bruce/0000-0001-5804-7061
FU National Institute on Drug Abuse-National Institutes of Health
[R21DA034394]; National Institute on Drug Abuse-National Institutes of
Health (Intramural Research Program grant)
FX This work was supported by the National Institute on Drug Abuse-National
Institutes of Health (Grant R21DA034394 to A.D.L. and Intramural
Research Program grant to Y.S. and B.T.H.).
NR 76
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 AUG 17
PY 2016
VL 36
IS 33
BP 8612
EP 8623
DI 10.1523/JNEUROSCI.1505-16.2016
PG 12
WC Neurosciences
SC Neurosciences & Neurology
GA DU6GW
UT WOS:000382313400009
PM 27535909
ER
PT J
AU Kaufman, DJ
Baker, R
Milner, LC
Devaney, S
Hudson, KL
AF Kaufman, David J.
Baker, Rebecca
Milner, Lauren C.
Devaney, Stephanie
Hudson, Kathy L.
TI A Survey of U.S Adults' Opinions about Conduct of a Nationwide Precision
Medicine Initiative (R) Cohort Study of Genes and Environment
SO PLOS ONE
LA English
DT Article
ID DATABASE; BIOBANK; HEART
AB Objectives
A survey of a population-based sample of U.S adults was conducted to measure their attitudes about, and inform the design of the Precision Medicine Initiative's planned national cohort study.
Methods
An online survey was conducted by GfK between May and June of 2015. The influence of different consent models on willingness to share data was examined by randomizing participants to one of eight consent scenarios.
Results
Of 4,777 people invited to take the survey, 2,706 responded and 2,601 (54% response rate) provided valid responses. Most respondents (79%) supported the proposed study, and 54% said they would definitely or probably participate if asked. Support for and willingness to participate in the study varied little among demographic groups; younger respondents, LGBT respondents, and those with more years of education were significantly more likely to take part if asked. The most important study incentive that the survey asked about was learning about one's own health information. Willingness to share data and samples under broad, study-by-study, menu and dynamic consent models was similar when a statement about transparency was included in the consent scenarios. Respondents were generally interested in taking part in several governance functions of the cohort study.
Conclusions
A large majority of the U.S. adults who responded to the survey supported a large national cohort study. Levels of support for the study and willingness to participate were both consistent across most demographic groups. The opportunity to learn health information about one's self from the study appears to be a strong motivation to participate.
C1 [Kaufman, David J.] NHGRI, Div Genom & Soc, NIH, Rockville, MD 20852 USA.
[Baker, Rebecca; Milner, Lauren C.; Devaney, Stephanie; Hudson, Kathy L.] NIH, Off Director, Bldg 10, Bethesda, MD 20892 USA.
RP Kaufman, DJ (reprint author), NHGRI, Div Genom & Soc, NIH, Rockville, MD 20852 USA.
EM dave.kaufman@nih.gov
FU Foundation for the National Institutes of Health
FX The authors wish to thank the Foundation for the National Institutes of
Health, which funded this survey. The authors would also like to thank
Vence Bonham, Laura Rodriguez, Alex Lee and the members of the Consent,
Education, Regulation and Consultation Working Group of the eMERGE
research consortium for their contributions to the survey and manuscript
development.; The Foundation for National Institutes of Health directly
paid for GfK to field the survey. The authors themselves received no
specific funding for the work. FNIH did not participate in data
collection, analysis, decisions to publish or preparation of the
manuscript. They were involved in discussions about the logistics of
study design but did not influence survey content.
NR 25
TC 3
Z9 3
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 AUG 17
PY 2016
VL 11
IS 8
AR e0160461
DI 10.1371/journal.pone.0160461
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DT4YN
UT WOS:000381487600031
ER
PT J
AU Frew, PM
Parker, K
Vo, L
Haley, D
O'Leary, A
Diallo, DD
Golin, CE
Kuo, I
Soto-Torres, L
Wang, J
Adimora, AA
Randall, LA
del Rio, C
Hodder, S
AF Frew, Paula M.
Parker, Kimberly
Vo, Linda
Haley, Danielle
O'Leary, Ann
Diallo, Dazon Dixon
Golin, Carol E.
Kuo, Irene
Soto-Torres, Lydia
Wang, Jing
Adimora, Adaora A.
Randall, Laura A.
del Rio, Carlos
Hodder, Sally
CA HIV Prevention Trials Network 064
TI Socioecological factors influencing women's HIV risk in the United
States: qualitative findings from the women's HIV SeroIncidence study
(HPTN 064)
SO BMC PUBLIC HEALTH
LA English
DT Article
DE HIV/AIDS; Sexual health; Socioecological model; Women; Minorities; HIV
risk reduction
ID SEXUALLY-TRANSMITTED INFECTIONS; INTIMATE PARTNER VIOLENCE;
AFRICAN-AMERICAN WOMEN; PREVENTION TRIALS NETWORK; NEIGHBORHOOD
DISADVANTAGE; DRUG-USERS; PERCEIVED DISCRIMINATION; DEPRESSIVE SYMPTOMS;
PHYSICAL HEALTH; SUBSTANCE-ABUSE
AB Background: We sought to understand the multilevel syndemic factors that are concurrently contributing to the HIV epidemic among women living in the US. We specifically examined community, network, dyadic, and individual factors to explain HIV vulnerability within a socioecological framework.
Methods: We gathered qualitative data (120 interviews and 31 focus groups) from a subset of women ages 18-44 years (N = 2,099) enrolled in the HPTN 064 HIV seroincidence estimation study across 10 US communities. We analyzed data from 4 diverse locations: Atlanta, New York City (the Bronx), Raleigh, and Washington, DC. Data were thematically coded using grounded theory methodology. Intercoder reliability was assessed to evaluate consistency of team-based coding practices.
Results: The following themes were identified at 4 levels including 1) exosystem (community): poverty prevalence, discrimination, gender imbalances, community violence, and housing challenges; 2) mesosystem (network): organizational social support and sexual concurrency; 3) microsystem (dyadic): sex exchange, interpersonal social support, intimate partner violence; and 4) individual: HIV/STI awareness, risk taking, and substance use. A strong theme emerged with over 80 % of responses linked to the fundamental role of financial insecurity underlying risktaking behavioral pathways.
Conclusions: Multilevel syndemic factors contribute to women's vulnerability to HIV in the US. Financial insecurity is a predominant theme, suggesting the need for tailored programming for women to reduce HIV risk.
C1 [Frew, Paula M.; Vo, Linda; Randall, Laura A.; del Rio, Carlos] Emory Univ, Div Infect Dis, Dept Med, Sch Med, 1760 Haygood Rd,Suite 300, Atlanta, GA 30322 USA.
[Frew, Paula M.; Haley, Danielle] Emory Rollins Sch Publ Hlth, Dept Behav Sci & Hlth Educ, 1518 Clifton Rd NE, Atlanta, GA 30322 USA.
[Frew, Paula M.; del Rio, Carlos] Emory Rollins Sch Publ Hlth, Hubert Dept Global Hlth, 1518 Clifton Rd NE, Atlanta, GA 30329 USA.
[Frew, Paula M.; del Rio, Carlos] Emory Univ, Emory Ctr AIDS Res, 1518 Clifton Rd NE,Suite 8050, Atlanta, GA 30322 USA.
[Parker, Kimberly] Texas Womans Univ, Dept Hlth Studies, CFO Bldg 1007,POB 425499, Denton, TX 76204 USA.
[O'Leary, Ann] Ctr Dis Control & Prevent, Div HIV AIDS Prevent, 1600 Clifton Rd, Atlanta, GA 30333 USA.
[Diallo, Dazon Dixon] SisterLove Inc, 3709 Bakers Ferry Rd SW, Atlanta, GA 30331 USA.
[Golin, Carol E.; Adimora, Adaora A.] Univ N Carolina, Sch Med, Dept Med, 130 Mason Farm Rd, Chapel Hill, NC 27599 USA.
[Kuo, Irene] George Washington Univ, Milken Inst, Sch Publ Hlth, 950 New Hampshire Ave NW,Suite 500, Washington, DC 20052 USA.
[Soto-Torres, Lydia] NIAID, Washington, DC USA.
[Wang, Jing] Fred Hutchinson Canc Res Ctr, SCHARP, 1124 Columbia St, Seattle, WA 98104 USA.
[Hodder, Sally] West Virginia Univ, Sch Med, One Med Ctr Dr,HSC South 2244, Morgantown, WV 26506 USA.
RP Frew, PM (reprint author), Emory Univ, Div Infect Dis, Dept Med, Sch Med, 1760 Haygood Rd,Suite 300, Atlanta, GA 30322 USA.; Frew, PM (reprint author), Emory Rollins Sch Publ Hlth, Dept Behav Sci & Hlth Educ, 1518 Clifton Rd NE, Atlanta, GA 30322 USA.; Frew, PM (reprint author), Emory Rollins Sch Publ Hlth, Hubert Dept Global Hlth, 1518 Clifton Rd NE, Atlanta, GA 30329 USA.; Frew, PM (reprint author), Emory Univ, Emory Ctr AIDS Res, 1518 Clifton Rd NE,Suite 8050, Atlanta, GA 30322 USA.
EM pfrew@emory.edu
RI del Rio, Carlos/B-3763-2012;
OI del Rio, Carlos/0000-0002-0153-3517; Frew, Paula/0000-0002-3078-9124
FU National Institute of Allergy and Infectious Diseases, National
Institute on Drug Abuse, and National Institute of Mental Health [UM1
AI068619, U01-AI068613, UM1-AI068613]; Centers for Innovative Research
to Control AIDS, Mailman School of Public Health, Columbia University
[5U1Al069466]; University of North Carolina Clinical Trials Unit
[AI069423]; University of North Carolina Clinical Trials Research Center
of the Clinical and Translational Science Award [RR 025747]; University
of North Carolina Center for AIDS Research [AI050410]; Emory University
HIV/AIDS Clinical Trials Unit [5UO1AI069418]; Center for AIDS Research
[P30 AI050409]; Clinical and Translational Science Award [UL1 RR025008];
Terry Beirn Community Programs for Clinical Research on AIDS Clinical
Trials Unit [5 UM1 AI069503-07]; Johns Hopkins Adult AIDS Clinical Trial
Unit [AI069465]; Johns Hopkins Clinical and Translational Science Award
[UL1 RR 25005]
FX Grant support provided by the National Institute of Allergy and
Infectious Diseases, National Institute on Drug Abuse, and National
Institute of Mental Health [UM1 AI068619, U01-AI068613, and
UM1-AI068613]; Centers for Innovative Research to Control AIDS, Mailman
School of Public Health, Columbia University [5U1Al069466]; University
of North Carolina Clinical Trials Unit [AI069423]; University of North
Carolina Clinical Trials Research Center of the Clinical and
Translational Science Award [RR 025747]; University of North Carolina
Center for AIDS Research [AI050410]; Emory University HIV/AIDS Clinical
Trials Unit [5UO1AI069418], Center for AIDS Research [P30 AI050409], and
Clinical and Translational Science Award [UL1 RR025008]; The Terry Beirn
Community Programs for Clinical Research on AIDS Clinical Trials Unit [5
UM1 AI069503-07], and; The Johns Hopkins Adult AIDS Clinical Trial Unit
[AI069465] and The Johns Hopkins Clinical and Translational Science
Award [UL1 RR 25005].
NR 95
TC 1
Z9 1
U1 9
U2 9
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 AUG 17
PY 2016
VL 16
AR 803
DI 10.1186/s12889-016-3364-7
PG 18
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA DT5UV
UT WOS:000381549400004
PM 27530401
ER
PT J
AU Maachani, UB
Tandle, A
Shankavaram, U
Kramp, T
Camphausen, K
AF Maachani, Uday B.
Tandle, Anita
Shankavaram, Uma
Kramp, Tamalee
Camphausen, Kevin
TI Modulation of miR-21 signaling by MPS1 in human glioblastoma
SO ONCOTARGET
LA English
DT Article
DE glioblastoma multiforme; MPS1; MiR21; PDCD4; MSH2; TGF-beta/SMAD
signaling
ID TUMOR-SUPPRESSOR GENE; BREAST-CANCER CELLS; MITOTIC CHECKPOINT;
COLORECTAL-CANCER; MICRORNA MATURATION; DIFFERENTIAL ROLES; PDCD4
EXPRESSION; RENAL FIBROSIS; PROTEIN; KINASE
AB Monopolar spindle 1 (MPS1) is an essential spindle assembly checkpoint (SAC) kinase involved in determining spindle integrity. Beyond its mitotic functions, it has been implicated in several other signaling pathways. Our earlier studies have elaborated on role of MPS1 in glioblastoma (GBM) radiosensitization. In this study using reverse phase protein arrays (RPPAs), we assessed MPS1 mediated cell signaling pathways and demonstrated that inhibiting MPS1 could upregulate the expression of the tumor suppressor PDCD4 and MSH2 genes, by down regulating micro RNA-21 (miR-21). In GBMs miR-21 expression is significantly elevated and is associated with chemo and radioresistance. Both MPS1 and miR-21 depletion suppressed GBM cell proliferation, whereas, ectopic expression of miR-21 rescued GBM cell growth from MPS1 inhibition. Further, we demonstrate that MPS1 mediates phosphorylation of SMAD3 but not SMAD2 in GBM cells; A possible mechanism behind miR-21 modulation by MPS1. Collectively, our results shed light onto an important role of MPS1 in TGF-beta/SMAD signaling via miR-21 regulation. We also, show the prognostic effect of miR-21, PDCD4 and MSH2 levels to patient survival across different GBM molecular subtypes. This scenario in which miR-21 is modulated by MPS1 inhibition may be exploited as a potential target for effective GBM therapy.
C1 [Maachani, Uday B.; Tandle, Anita; Shankavaram, Uma; Kramp, Tamalee; Camphausen, Kevin] NCI, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA.
RP Camphausen, K (reprint author), NCI, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA.
EM camphauk@mail.nih.gov
FU Intramural Research Program of the National Institutes of Health,
National Cancer Institute
FX This research was supported by the Intramural Research Program of the
National Institutes of Health, National Cancer Institute.
NR 54
TC 0
Z9 0
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 AUG 16
PY 2016
VL 7
IS 33
BP 52912
EP 52927
DI 10.18632/oncotarget.4143
PG 16
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA DY9DG
UT WOS:000385433000024
PM 25991676
ER
PT J
AU Wang, J
He, PJ
Gaida, M
Yang, SH
Schetter, AJ
Gaedcke, J
Ghadimi, BM
Ried, T
Yfantis, H
Lee, D
Weiss, JM
Stauffer, J
Hanna, N
Alexander, HR
Hussain, SP
AF Wang, Jian
He, Peijun
Gaida, Matthias
Yang, Shouhui
Schetter, Aaron J.
Gaedcke, Jochen
Ghadimi, B. Michael
Ried, Thomas
Yfantis, Harris
Lee, Dong
Weiss, Jonathan M.
Stauffer, Jimmy
Hanna, Nader
Alexander, H. Richard
Hussain, S. Perwez
TI Inducible nitric oxide synthase enhances disease aggressiveness in
pancreatic cancer
SO ONCOTARGET
LA English
DT Article
DE NOS2; NO; PDAC; KPC mouse model
ID FORKHEAD TRANSCRIPTION FACTOR; DUCTAL ADENOCARCINOMA; BREAST-CANCER;
INFLAMMATION; SURVIVAL; TUMORIGENESIS; INVASION; GROWTH; FOXOS; CELLS
AB Pancreatic cancer is one of the most lethal malignancies and is refractory to the available treatments. Pancreatic ductal adenocarcinoma (PDAC) expresses high level of inducible nitric oxide synthase (NOS2), which causes sustained production of nitric oxide (NO). We tested the hypothesis that an aberrantly increased NO-release enhances the development and progression of PDAC. Enhanced NOS2 expression in tumors significantly associated with poor survival in PDAC patients (N = 107) with validation in independent cohorts. We then genetically targeted NOS2 in an autochthonous mouse model of PDAC to examine the effect of NOS2-deficiency on disease progression and survival. Genetic ablation of NOS2 significantly prolonged survival and reduced tumor severity in LSL-Kras(G12D/+); LSL-Trp53(R172H/+); Pdx-1-Cre (KPC) mice. Primary tumor cells isolated from NOS2-deficient KPC (NKPC) mice showed decreased proliferation and invasiveness as compared to those from KPC mice. Furthermore, NKPC tumors showed reduced expression of pERK, a diminished inactivation of Forkhead box transcription factor O (FOXO3), a tumor suppressor, and a decrease in the expression of oncomir-21, when compared with tumors in KPC mice. Taken together, these findings showed that NOS2 is a predictor of prognosis in early stage, resected PDAC patients, and provide proof-of-principle that targeting NOS2 may have potential therapeutic value in this lethal malignancy.
C1 [Wang, Jian; He, Peijun; Yang, Shouhui; Hussain, S. Perwez] NCI, Pancreat Canc Unit, Human Carcinogenesis Lab, CCR, Bethesda, MD 20892 USA.
[Gaida, Matthias] Univ Heidelberg Hosp, Inst Pathol, Heidelberg, Germany.
[Schetter, Aaron J.] US FDA, Silver Spring, MD USA.
[Gaedcke, Jochen; Ghadimi, B. Michael] Univ Med, Dept Gen Visceral & Pediat Surg, Gottingen, Germany.
[Ried, Thomas] NCI, Genet Branch, CCR, Baltimore Vet Affairs Med Ctr, Baltimore, MD USA.
[Yfantis, Harris; Lee, Dong] Baltimore Vet Affairs Med Ctr, Pathol & Lab Med, Baltimore, MD USA.
[Weiss, Jonathan M.] NCI, Canc & Inflammat Program, CCR, Frederick, MD 21701 USA.
[Stauffer, Jimmy] NCI, Lab Cell & Dev Signaling, Frederick, MD 21701 USA.
[Hanna, Nader; Alexander, H. Richard] Univ Maryland, Sch Med, Div Surg Oncol, Baltimore, MD 21201 USA.
RP Hussain, SP (reprint author), NCI, Pancreat Canc Unit, Human Carcinogenesis Lab, CCR, Bethesda, MD 20892 USA.
EM hussainp@mail.nih.gov
FU Intramural Research Program of Center for Cancer Research, National
Cancer Institute, NIH
FX Intramural Research Program of the Center for Cancer Research, National
Cancer Institute, NIH.
NR 45
TC 0
Z9 0
U1 2
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 AUG 16
PY 2016
VL 7
IS 33
BP 52993
EP 53004
DI 10.18632/oncotarget.10323
PG 12
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA DY9DG
UT WOS:000385433000029
PM 27367029
ER
PT J
AU Fu, SW
Kirolikar, SP
Ginsburg, E
Tan, XH
Schwartz, A
Simmens, SJ
Man, YG
Pinzone, JJ
Teal, C
Awate, S
Vonderhaar, BK
Berg, PE
AF Fu, Sidney W.
Kirolikar, Saurabh P.
Ginsburg, Erika
Tan, Xiaohui
Schwartz, Arnold
Simmens, Samuel J.
Man, Yan-gao
Pinzone, Joseph J.
Teal, Christine
Awate, Sanket
Vonderhaar, Barbara K.
Berg, Patricia E.
TI Beta protein 1 homeoprotein induces cell growth and estrogen-independent
tumorigenesis by binding to the estrogen receptor in breast cancer
SO ONCOTARGET
LA English
DT Article
DE homeobox gene; BP1; estrogen receptor; tamoxifen resistance;
tumorigenesis
ID GENOME-WIDE ANALYSIS; HOMEOBOX GENE; ER-ALPHA; TAMOXIFEN RESISTANCE;
BRCA1 INHIBITION; EXPRESSION; BP1; TUMORS; CARCINOMA; SURVIVAL
AB Expression of Beta Protein 1 (BP1), a homeotic transcription factor, increases during breast cancer progression and may be associated with tumor aggressiveness. In our present work, we investigate the influence of BP1 on breast tumor formation and size in vitro and in vivo. Cells overexpressing BP1 showed higher viability when grown in the absence of serum (p < 0.05), greater invasive potential (p < 0.05) and formed larger colonies (p < 0.004) compared with the controls. To determine the influence of BP1 overexpression on tumor characteristics, MCF-7 cells transfected with either empty vector (V1) or overexpressor plasmids (O2 and O4) were injected into the fat pads of athymic nude mice. Tumors grew larger in mice receiving O2 or O4 cells than in mice receiving V1 cells. Moreover, BP1 mRNA expression levels were positively correlated with tumor size in patients (p = 0.01). Interestingly, 20% of mice injected with O2 or O4 cells developed tumors in the absence of estrogen, while no mice receiving V1 cells developed tumors. Several mechanisms of estrogen independent tumor formation related to BP1 were established. These data are consistent with the fact that expression of breast cancer anti-estrogen resistance 1 (BCAR1) was increased in O2 compared to V1 cells (p < 0.01). Importantly, O2 cells exhibited increased proliferation when treated with tamoxifen, while V1 cells showed growth inhibition. Overall, BP1 overexpresssion in MCF-7 breast cancer cells leads to increased cell growth, estrogen-independent tumor formation, and increased proliferation. These findings suggest that BP1 may be an important biomarker and therapeutic target in ER positive breast cancer.
C1 [Fu, Sidney W.; Tan, Xiaohui] George Washington Univ, Dept Med, Div Genom Med, Washington, DC 20037 USA.
[Kirolikar, Saurabh P.; Awate, Sanket; Berg, Patricia E.] George Washington Univ, Dept Biochem & Mol Med, Washington, DC 20037 USA.
[Ginsburg, Erika; Vonderhaar, Barbara K.] NCI, Mammary Biol & Tumorigenesis Lab, NIH, Bethesda, MD 20892 USA.
[Schwartz, Arnold] George Washington Univ, Med Ctr, Dept Pathol, Washington, DC 20037 USA.
[Simmens, Samuel J.] George Washington Univ, Sch Publ Hlth & Hlth Serv, Dept Epidemiol & Biostat, Washington, DC 20037 USA.
[Man, Yan-gao] Armed Forces Inst Pathol, Dept Gynecol & Breast Pathol, Washington, DC 20306 USA.
[Pinzone, Joseph J.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA.
[Teal, Christine] George Washington Univ, Dept Surg, Washington, DC 20037 USA.
RP Berg, PE (reprint author), George Washington Univ, Dept Biochem & Mol Med, Washington, DC 20037 USA.
EM peb@gwu.edu
FU Intramural Research Program of the NIH; Center for Cancer Research; NCI;
Elaine H. Snyder Cancer Research Award (SWF); Katherine Birch McCormick
Foundation (PEB); [K08 CA102875]
FX Portions of this research were supported by grant K08 CA102875 (JJP), by
the Intramural Research Program of the NIH, Center for Cancer Research,
NCI (E.G. and B.K.V.), the Elaine H. Snyder Cancer Research Award (SWF)
and by the Katherine Birch McCormick Foundation (PEB).
NR 53
TC 0
Z9 0
U1 0
U2 0
PU IMPACT JOURNALS LLC
PI ALBANY
PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA
SN 1949-2553
J9 ONCOTARGET
JI Oncotarget
PD AUG 16
PY 2016
VL 7
IS 33
BP 53204
EP 53216
DI 10.18632/oncotarget.10633
PG 13
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA DY9DG
UT WOS:000385433000045
PM 27449292
ER
PT J
AU Cousin, SF
Kaderavek, P
Haddou, B
Charlier, C
Marquardsen, T
Tyburn, JM
Bovier, PA
Engelke, F
Maas, W
Bodenhausen, G
Pelupessy, P
Ferrage, F
AF Cousin, Samuel F.
Kaderavek, Pavel
Haddou, Baptiste
Charlier, Cyril
Marquardsen, Thorsten
Tyburn, Jean-Max
Bovier, Pierre-Alain
Engelke, Frank
Maas, Werner
Bodenhausen, Geoffrey
Pelupessy, Philippe
Ferrage, Fabien
TI Recovering Invisible Signals by Two-Field NMR Spectroscopy
SO ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
LA English
DT Article
DE chemical exchange; high-field NMR spectroscopy; kinetics; nuclear
magnetic resonance; low-field NMR spectroscopy
ID MAGNETIC-RELAXATION DISPERSION; MOLECULAR-WEIGHT PROTEINS; FIELD-CYCLING
DEVICE; CONTRAST AGENTS; MOLTEN GLOBULE; RESOLUTION; DYNAMICS;
RELAXOMETRY; RESONANCE; NANOSECOND
AB Nuclear magnetic resonance (NMR) studies have benefited tremendously from the steady increase in the strength of magnetic fields. Spectacular improvements in both sensitivity and resolution have enabled the investigation of molecular systems of rising complexity. At very high fields, this progress may be jeopardized by line broadening, which is due to chemical exchange or relaxation by chemical shift anisotropy. In this work, we introduce a two-field NMR spectrometer designed for both excitation and observation of nuclear spins in two distinct magnetic fields in a single experiment. NMR spectra of several small molecules as well as a protein were obtained, with two dimensions acquired at vastly different magnetic fields. Resonances of exchanging groups that are broadened beyond recognition at high field can be sharpened to narrow peaks in the low-field dimension. Two-field NMR spectroscopy enables the measurement of chemical shifts at optimal fields and the study of molecular systems that suffer from internal dynamics, and opens new avenues for NMR spectroscopy at very high magnetic fields.
C1 [Cousin, Samuel F.; Kaderavek, Pavel; Haddou, Baptiste; Charlier, Cyril; Bodenhausen, Geoffrey; Pelupessy, Philippe; Ferrage, Fabien] PSL Res Univ, Ecole Normale Super, Dept Chem, 24 Rue Lhomond, F-75005 Paris, France.
[Cousin, Samuel F.; Kaderavek, Pavel; Haddou, Baptiste; Charlier, Cyril; Bodenhausen, Geoffrey; Pelupessy, Philippe; Ferrage, Fabien] Univ Paris 06, Sorbonne Univ, LBM 4 Pl Jussieu, F-75005 Paris, France.
[Cousin, Samuel F.; Kaderavek, Pavel; Charlier, Cyril; Bodenhausen, Geoffrey; Pelupessy, Philippe; Ferrage, Fabien] CNRS, UMR LBM 7203, F-75005 Paris, France.
[Haddou, Baptiste] CNRS, UMR Pasteur 8640, F-75005 Paris, France.
[Marquardsen, Thorsten; Engelke, Frank] Bruker BioSpin GmbH, Silberstreifen 4, D-76287 Rheinstetten, Germany.
[Tyburn, Jean-Max] Bruker BioSpin, 34 Rue Ind BP 10002, F-67166 Wissembourg, France.
[Bovier, Pierre-Alain] Bruker BioSpin AG, Ind Str 26, CH-8117 Fallanden, Switzerland.
[Maas, Werner] Bruker BioSpin, Billerica, MA 01821 USA.
[Charlier, Cyril] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
RP Ferrage, F (reprint author), PSL Res Univ, Ecole Normale Super, Dept Chem, 24 Rue Lhomond, F-75005 Paris, France.; Ferrage, F (reprint author), Univ Paris 06, Sorbonne Univ, LBM 4 Pl Jussieu, F-75005 Paris, France.; Ferrage, F (reprint author), CNRS, UMR LBM 7203, F-75005 Paris, France.
EM Fabien.Ferrage@ens.fr
RI Kaderavek, Pavel/D-7670-2012
FU European Research Council (ERC) under the European Community Seventh
Framework Program [279519 (2F4BIODYN)]
FX We thank Kaushik Dutta (New York Structural Biology Center) for the
ubiquitin plasmid as well as Lei Bruschweiler-Li and Rafael Bruschweiler
(the Ohio State University) for the method for ubiquitin purification.
This work was funded by the European Research Council (ERC) under the
European Community Seventh Framework Program (FP7/2007-2013), ERC Grant
Agreement 279519 (2F4BIODYN).
NR 48
TC 1
Z9 1
U1 22
U2 22
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 AUG 16
PY 2016
VL 55
IS 34
BP 9886
EP 9889
DI 10.1002/anie.201602978
PG 4
WC Chemistry, Multidisciplinary
SC Chemistry
GA DW0ZT
UT WOS:000383373000009
PM 27417269
ER
PT J
AU Ahlawat, S
Fayad, LM
Khan, MS
Bredella, MA
Harris, GJ
Evans, DG
Farschtschi, S
Jacobs, MA
Chhabra, A
Salamon, JM
Wenzel, R
Mautner, VF
Dombi, E
Cai, WL
Plotkin, SR
Blakeley, JO
AF Ahlawat, Shivani
Fayad, Laura M.
Khan, Muhammad Shayan
Bredella, Miriam A.
Harris, Gordon J.
Evans, D. Gareth
Farschtschi, Said
Jacobs, Michael A.
Chhabra, Avneesh
Salamon, Johannes M.
Wenzel, Ralph
Mautner, Victor F.
Dombi, Eva
Cai, Wenli
Plotkin, Scott R.
Blakeley, Jaishri O.
CA Whole Body MRI Comm REiNS
TI Current whole-body MRI applications in the neurofibromatoses NF1, NF2,
and schwannomatosis
SO NEUROLOGY
LA English
DT Article
ID NERVE SHEATH TUMORS; PLEXIFORM NEUROFIBROMAS; INTRAOBSERVER VARIABILITY;
DIAGNOSTIC-CRITERIA; METASTATIC-DISEASE; BURDEN; TYPE-1; GROWTH;
INTEROBSERVER; FEASIBILITY
AB Objectives: The Response Evaluation in Neurofibromatosis and Schwannomatosis (REiNS) International Collaboration Whole-Body MRI (WB-MRI) Working Group reviewed the existing literature on WB-MRI, an emerging technology for assessing disease in patients with neurofibromatosis type 1 (NF1), neurofibromatosis type 2 (NF2), and schwannomatosis (SWN), to recommend optimal image acquisition and analysis methods to enable WB-MRI as an endpoint in NF clinical trials.
Methods: A systematic process was used to review all published data about WB-MRI in NF syndromes to assess diagnostic accuracy, feasibility and reproducibility, and data about specific techniques for assessment of tumor burden, characterization of neoplasms, and response to therapy.
Results: WB-MRI at 1.5T or 3.0T is feasible for image acquisition. Short tau inversion recovery (STIR) sequence is used in all investigations to date, suggesting consensus about the utility of this sequence for detection of WB tumor burden in people with NF. There are insufficient data to support a consensus statement about the optimal imaging planes (axial vs coronal) or 2D vs 3D approaches. Functional imaging, although used in some NF studies, has not been systematically applied or evaluated. There are no comparative studies between regional vs WB-MRI or evaluations of WB-MRI reproducibility.
Conclusions: WB-MRI is feasible for identifying tumors using both 1.5T and 3.0T systems. The STIR sequence is a core sequence. Additional investigation is needed to define the optimal approach for volumetric analysis, the reproducibility of WB-MRI in NF, and the diagnostic performance of WB-MRI vs regional MRI.
C1 [Ahlawat, Shivani; Fayad, Laura M.; Jacobs, Michael A.] Johns Hopkins Univ, Russell H Morgan Dept Radiol & Radiol Sci, Baltimore, MD USA.
[Jacobs, Michael A.] Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA.
[Blakeley, Jaishri O.] Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21218 USA.
[Khan, Muhammad Shayan] Khyber Med Coll, Peshawar, Pakistan.
[Bredella, Miriam A.; Harris, Gordon J.; Cai, Wenli] Massachusetts Gen Hosp, Dept Radiol, Boston, MA USA.
Harvard Med Sch, Boston, MA USA.
[Evans, D. Gareth] Univ Manchester, Manchester Acad Hlth Sci Ctr, Genom Med, Manchester M13 9PL, Lancs, England.
[Farschtschi, Said; Mautner, Victor F.] Univ Med Ctr Hamburg Eppendorf, Dept Neurol, Hamburg, Germany.
[Chhabra, Avneesh] Univ Texas Southwestern Med Ctr Dallas, Radiol & Orthoped Surg, Dallas, TX 75390 USA.
[Salamon, Johannes M.] Univ Hosp Hamburg Eppendorf, Dept Diagnost & Intervent Radiol, Hamburg, Germany.
[Wenzel, Ralph] Radiol Practice Altona, Hamburg, Germany.
[Dombi, Eva] NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA.
[Plotkin, Scott R.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
[Plotkin, Scott R.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA.
RP Ahlawat, S (reprint author), Johns Hopkins Univ, Russell H Morgan Dept Radiol & Radiol Sci, Baltimore, MD USA.
EM sahlawa1@jhmi.edu
RI North, Kathryn/K-6476-2012;
OI North, Kathryn/0000-0003-0841-8009; Evans, Gareth/0000-0002-8482-5784
FU NICHD NIH HHS [U54 HD090255]
NR 37
TC 1
Z9 1
U1 1
U2 1
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 AUG 16
PY 2016
VL 87
SU 1
BP S31
EP S39
DI 10.1212/WNL.0000000000002929
PG 9
WC Clinical Neurology
SC Neurosciences & Neurology
GA DU6MD
UT WOS:000382328100006
PM 27527647
ER
PT J
AU Hanemann, CO
Blakeley, JO
Nunes, FP
Robertson, K
Stemmer-Rachamimov, A
Mautner, V
Kurtz, A
Ferguson, M
Widemann, BC
Evans, DG
Ferner, R
Carroll, SL
Korf, B
Wolkenstein, P
Knight, P
Plotkin, SR
AF Hanemann, C. Oliver
Blakeley, Jaishri O.
Nunes, Fabio P.
Robertson, Kent
Stemmer-Rachamimov, Anat
Mautner, Victor
Kurtz, Andreas
Ferguson, Michael
Widemann, Brigitte C.
Evans, D. Gareth
Ferner, Rosalie
Carroll, Steven L.
Korf, Bruce
Wolkenstein, Pierre
Knight, Pamela
Plotkin, Scott R.
CA REiNS Int Collaboration
TI Current status and recommendations for biomarkers and biobanking in
neurofibromatosis
SO NEUROLOGY
LA English
DT Article
ID NERVE-SHEATH TUMORS; CLINICAL-TRIALS; TYPE-1; SERUM; MANAGEMENT;
EXPRESSION; DIAGNOSIS; CONSENSUS
AB Objective: Clinically validated biomarkers for neurofibromatosis 1 (NF1), neurofibromatosis 2 (NF2), and schwannomatosis (SWN) have not been identified to date. The biomarker working group's goals are to (1) define biomarker needs in NF1, NF2, and SWN; (2) summarize existing data on biomarkers in NF1, NF2, and SWN; (3) outline recommendations for sample collection and biomarker development; and (4) standardize sample collection and methodology protocols where possible to promote comparison between studies by publishing standard operating procedures (SOPs).
Methods: The biomarker group reviewed published data on biomarkers in NF1, NF2, and SWN and on biobanking efforts outside these diseases via literature search, defined the need for biomarkers in NF, and developed recommendations in a series of consensus meetings.
Results: We describe existing biomarkers in NF and report consensus recommendations for SOP and a minimal clinical dataset to accompany samples derived from patients with NF1, NF2, and SWN in decentralized biobanks.
Conclusions: These recommendations are intended to provide clinicians and researchers with a common set of guidelines to collect and store biospecimens and for establishment of biobanks for NF1, NF2, and SWN.
C1 [Hanemann, C. Oliver] Univ Plymouth, Peninsula Sch Med & Dent, Inst Translat & Stratified Med, Plymouth, Devon, England.
[Blakeley, Jaishri O.] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA.
[Nunes, Fabio P.] Indiana Univ, Dept Pediat, Bloomington, IN 47405 USA.
[Robertson, Kent; Ferguson, Michael] Indiana Univ, Dept Pediat, Sch Med, Bloomington, IN 47405 USA.
[Nunes, Fabio P.] Eli Lilly & Co, Tailored Therapeut, Indianapolis, IN 46285 USA.
[Stemmer-Rachamimov, Anat] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Plotkin, Scott R.] Massachusetts Gen Hosp, Neurooncol, Boston, MA 02114 USA.
[Mautner, Victor] Uniklin Eppendorf, Neurol Klin, Hamburg, Germany.
[Kurtz, Andreas] Charite, Berlin Brandenburg Ctr Regenerat Therapies, Berlin, Germany.
[Kurtz, Andreas] Seoul Natl Univ, Coll Vet Med, Seoul, South Korea.
[Kurtz, Andreas] Seoul Natl Univ, Res Inst Vet Sci, Seoul, South Korea.
[Widemann, Brigitte C.] NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA.
[Evans, D. Gareth] Univ Manchester, Genom Med, Manchester M13 9PL, Lancs, England.
[Ferner, Rosalie] Guys & St Thomas NHS Fdn Trust, Dept Neurol, Natl Neurofibromatosis Serv, London, England.
[Carroll, Steven L.] Med Univ S Carolina, Dept Pathol & Lab Med, Charleston, SC 29425 USA.
[Korf, Bruce] Univ Alabama Birmingham, Heflin Ctr Genom Sci, Birmingham, AL USA.
GHU Henri Mondor, Paris, France.
[Knight, Pamela] Childrens Tumor Fdn, New York, NY USA.
RP Hanemann, CO (reprint author), Univ Plymouth, Peninsula Sch Med & Dent, Inst Translat & Stratified Med, Plymouth, Devon, England.
EM Oliver.Hanemann@plymouth.ac.uk
RI North, Kathryn/K-6476-2012;
OI North, Kathryn/0000-0003-0841-8009; Hanemann, Clemens
Oliver/0000-0002-1951-1025; Evans, Gareth/0000-0002-8482-5784
FU NICHD NIH HHS [U54 HD090255]
NR 22
TC 1
Z9 1
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 AUG 16
PY 2016
VL 87
SU 1
BP S40
EP S48
DI 10.1212/WNL.0000000000002932
PG 9
WC Clinical Neurology
SC Neurosciences & Neurology
GA DU6MD
UT WOS:000382328100007
PM 27527649
ER
PT J
AU Plotkin, SR
Davis, SD
Robertson, KA
Akshintala, S
Allen, J
Fisher, MJ
Blakeley, JO
Widemann, BC
Ferner, RE
Marcus, CL
AF Plotkin, Scott R.
Davis, Stephanie D.
Robertson, Kent A.
Akshintala, Srivandana
Allen, Julian
Fisher, Michael J.
Blakeley, Jaishri O.
Widemann, Brigitte C.
Ferner, Rosalie E.
Marcus, Carole L.
CA REiNS Int Collaboration
TI Sleep and pulmonary outcomes for clinical trials of airway plexiform
neurofibromas in NF1
SO NEUROLOGY
LA English
DT Article
ID PHASE-I TRIAL; APNEA SYNDROME; REFERENCE VALUES; RESPIRATORY
INDICATIONS; PRACTICE PARAMETERS; CYSTIC-FIBROSIS; CPAP TREATMENT;
CHILDREN; POLYSOMNOGRAPHY; SPIROMETRY
AB Objective: Plexiform neurofibromas (PNs) are complex, benign nerve sheath tumors that occur in approximately 25%-50% of individuals with neurofibromatosis type 1 (NF1). PNs that cause airway compromise or pulmonary dysfunction are uncommon but clinically important. Because improvement in sleep quality or airway function represents direct clinical benefit, measures of sleep and pulmonary function may be more meaningful than tumor size as endpoints in therapeutic clinical trials targeting airway PN.
Methods: The Response Evaluation in Neurofibromatosis and Schwannomatosis functional outcomes group reviewed currently available endpoints for sleep and pulmonary outcomes and developed consensus recommendations for response evaluation in NF clinical trials.
Results: For patients with airway PNs, polysomnography, impulse oscillometry, and spirometry should be performed to identify abnormal function that will be targeted by the agent under clinical investigation. The functional group endorsed the use of the apnea hypopnea index (AHI) as the primary sleep endpoint, and pulmonary resistance at 10 Hz (R-10) or forced expiratory volume in 1 or 0.75 seconds (FEV1 or FEV0.75) as primary pulmonary endpoints. The group defined minimum changes in AHI, R-10, and FEV1 or FEV0.75 for response criteria. Secondary sleep outcomes include desaturation and hypercapnia during sleep and arousal index. Secondary pulmonary outcomes include pulmonary resistance and reactance measurements at 5, 10, and 20 Hz; forced vital capacity; peak expiratory flow; and forced expiratory flows.
Conclusions: These recommended sleep and pulmonary evaluations are intended to provide researchers with a standardized set of clinically meaningful endpoints for response evaluation in trials of NF1-related airway PNs.
C1 [Plotkin, Scott R.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
[Plotkin, Scott R.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA.
[Davis, Stephanie D.] Indiana Univ Sch Med, Riley Childrens Hosp, Sect Pediat Pulmonol Allergy & Sleep Med, Indianapolis, IN 46202 USA.
[Robertson, Kent A.] Indiana Univ Sch Med, Riley Childrens Hosp, Stem Cell Transplantat Program, Indianapolis, IN 46202 USA.
[Akshintala, Srivandana; Widemann, Brigitte C.] NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA.
[Allen, Julian] Childrens Hosp Philadelphia, Div Pulm Med, Philadelphia, PA 19104 USA.
[Fisher, Michael J.] Childrens Hosp Philadelphia, Div Oncol, Philadelphia, PA 19104 USA.
[Marcus, Carole L.] Childrens Hosp Philadelphia, Sleep Ctr, Philadelphia, PA 19104 USA.
[Fisher, Michael J.] Univ Penn, Dept Pediat, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Marcus, Carole L.] Univ Penn, Sleep Ctr, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Allen, Julian] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Blakeley, Jaishri O.] Johns Hopkins Med Inst, Dept Neurol, Baltimore, MD 21205 USA.
[Ferner, Rosalie E.] Guys & St Thomas NHS Fdn Trust, Dept Neurol, London, England.
Kings Coll London, Inst Psychiat, London WC2R 2LS, England.
RP Plotkin, SR (reprint author), Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.; Plotkin, SR (reprint author), Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA.
EM splotkin@partners.org
RI North, Kathryn/K-6476-2012;
OI North, Kathryn/0000-0003-0841-8009; Evans, Gareth/0000-0002-8482-5784
FU NICHD NIH HHS [U54 HD090255]
NR 42
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 0028-3878
EI 1526-632X
J9 NEUROLOGY
JI Neurology
PD AUG 16
PY 2016
VL 87
SU 1
BP S13
EP S20
DI 10.1212/WNL.0000000000002933
PG 8
WC Clinical Neurology
SC Neurosciences & Neurology
GA DU6MD
UT WOS:000382328100004
PM 27527645
ER
PT J
AU Walsh, KS
Janusz, J
Wolters, PL
Martin, S
Klein-Tasman, BP
Toledo-Tamula, MA
Thompson, HL
Payne, JM
Hardy, KK
de Blank, P
Semerjian, C
Gray, LS
Solomon, SE
Ullrich, N
AF Walsh, Karin S.
Janusz, Jennifer
Wolters, Pamela L.
Martin, Staci
Klein-Tasman, Bonita P.
Toledo-Tamula, Mary Anne
Thompson, Heather L.
Payne, Jonathan M.
Hardy, Kristina K.
de Blank, Peter
Semerjian, Claire
Gray, Laura Schaffner
Solomon, Sondra E.
Ullrich, Nicole
CA REiNS Int Collaboration
TI Neurocognitive outcomes in neurofibromatosis clinical trials
Recommendations for the domain of attention
SO NEUROLOGY
LA English
DT Article
ID CONSENSUS COGNITIVE BATTERY; DEFICIT/HYPERACTIVITY DISORDER; TYPE-1;
CHILDREN; ADHD; DEFICITS; NF1; SPAN; METHYLPHENIDATE; COMPLICATION
AB Neurofibromatosis type 1 (NF1) is associated with neurocognitive deficits that can impact everyday functioning of children, adolescents, and adults with this disease. However, there is little agreement regarding measures to use as cognitive endpoints in clinical trials. This article describes the work of the Neurocognitive Committee of the Response Evaluation in Neurofibromatosis and Schwannomatosis (REiNS) International Collaboration. The goal of this committee is to identify standardized and specific cognitive assessment tools for use in NF clinical trials. The committee first identified cognitive domains relevant to NF1 and prioritized attention as the first domain of focus given prior and current trends in NF1 cognitive clinical trials. Performance measures and behavioral rating questionnaires of attention were reviewed by the group using established criteria to assess patient characteristics, psychometric properties, and feasibility. The highest rated tests underwent side-by-side comparison. The Digit Span subtest from the Wechsler scales was given the highest ratings of the performance measures due to its good psychometrics, feasibility, utility across a wide age range, and extensive use in previous research. The Conners scales achieved the highest ratings of the behavioral questionnaires for similar reasons. Future articles will focus on other cognitive domains, with the ultimate goal of achieving agreement for cognitive endpoints that can be used across NF clinical trials.
C1 [Walsh, Karin S.; Hardy, Kristina K.] George Washington Sch Med, Childrens Natl Hlth Syst, Washington, DC 20052 USA.
[Janusz, Jennifer] Univ Colorado, Sch Med, Childrens Hosp Colorado, Aurora, CO USA.
[Wolters, Pamela L.; Martin, Staci] NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA.
[Klein-Tasman, Bonita P.] Univ Wisconsin, Milwaukee, WI 53201 USA.
[Toledo-Tamula, Mary Anne] NCI, Clin Res Directorate, Clin Monitoring Res Program, Leidos Biomed Res Inc, Frederick, MD 21701 USA.
[Thompson, Heather L.] Calif State Univ Sacramento, Sacramento, CA 95819 USA.
[Payne, Jonathan M.] Murdoch Childrens Res Inst, Parkville, Vic, Australia.
[de Blank, Peter] Rainbow Babies & Childrens Hosp, 2101 Adelbert Rd, Cleveland, OH 44106 USA.
[Semerjian, Claire] Roosevelt Univ, Chicago, IL 60605 USA.
[Gray, Laura Schaffner; Ullrich, Nicole] Boston Childrens Hosp, Boston, MA USA.
[Solomon, Sondra E.] Univ Vermont, Burlington, VT 05405 USA.
RP Walsh, KS (reprint author), George Washington Sch Med, Childrens Natl Hlth Syst, Washington, DC 20052 USA.
EM kwalsh@childrensnational.org
RI North, Kathryn/K-6476-2012;
OI North, Kathryn/0000-0003-0841-8009; Payne, Jonathan/0000-0001-9565-3845;
Evans, Gareth/0000-0002-8482-5784
FU NICHD NIH HHS [U54 HD090255]
NR 50
TC 0
Z9 0
U1 1
U2 1
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 AUG 16
PY 2016
VL 87
SU 1
BP S21
EP S30
DI 10.1212/WNL.0000000000002928
PG 10
WC Clinical Neurology
SC Neurosciences & Neurology
GA DU6MD
UT WOS:000382328100005
PM 27527646
ER
PT J
AU Widemann, BC
Plotkin, SR
AF Widemann, Brigitte C.
Plotkin, Scott R.
TI Consensus for NF clinical trials Recommendations of the REiNS
collaboration (Supplement II) INTRODUCTION
SO NEUROLOGY
LA English
DT Editorial Material
ID PROGRESSIVE VESTIBULAR SCHWANNOMAS; INTERNATIONAL COLLABORATION;
NEUROFIBROMATOSIS TYPE-2; PHASE-II; OUTCOMES
AB The neurofibromatoses (NFs) can result in substantial morbidity in affected patients. In order to accelerate the development of effective therapies for NF-related tumor and nontumor manifestations, the development of standardized meaningful outcome measures for clinical trials is critical. The Response Evaluation in Neurofibromatosis and Schwannomatosis (REiNS) International Collaboration was established with the goal to develop consensus recommendations for outcome measures and endpoints in future NF trials and provided the first set of recommendations in a Neurology (R) supplement in 2013. This second supplement updates on clinical trials that have incorporated the recommended measures and provides new recommendations for (1) standardized and specific cognitive assessment tools for use in NF clinical trials, (2) patient-reported outcome measures including pain and physical functioning, (3) functional outcome measures for airway plexiform neurofibromas, (4) the use of whole-body MRI in NF, and (5) the development of biomarkers in NF and guidelines for collection of biospecimens and establishment of biobanks for neurofibromatosis 1 (NF1), neurofibromatosis 2 (NF2), and schwannomatosis. Through engagement of the NF research community, regulatory agencies, NF advocacy groups, industry, and patients with NF, REiNS will provide a framework for comprehensive review of these recommendations, continue development of outcome measures relevant to patients, and compare results of trials, which use identical outcome measures.
C1 [Widemann, Brigitte C.] NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA.
[Plotkin, Scott R.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA.
RP Widemann, BC (reprint author), NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA.
EM widemanb@mail.nih.gov
NR 14
TC 0
Z9 0
U1 1
U2 1
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 AUG 16
PY 2016
VL 87
SU 1
BP S1
EP S3
DI 10.1212/WNL.0000000000002930
PG 3
WC Clinical Neurology
SC Neurosciences & Neurology
GA DU6MD
UT WOS:000382328100001
ER
PT J
AU Wolters, PL
Martin, S
Merker, VL
Tonsgard, JH
Solomon, SE
Baldwin, A
Bergner, AL
Walsh, K
Thompson, HL
Gardner, KL
Hingtgen, CM
Schorry, E
Dudley, WN
Franklin, B
AF Wolters, Pamela L.
Martin, Staci
Merker, Vanessa L.
Tonsgard, James H.
Solomon, Sondra E.
Baldwin, Andrea
Bergner, Amanda L.
Walsh, Karin
Thompson, Heather L.
Gardner, Kathy L.
Hingtgen, Cynthia M.
Schorry, Elizabeth
Dudley, William N.
Franklin, Barbara
CA REiNS Int Collaboration
TI Patient-reported outcomes of pain and physical functioning in
neurofibromatosis clinical trials
SO NEUROLOGY
LA English
DT Article
ID QUALITY-OF-LIFE; PROMISA(R) PEDIATRIC SCALES; INFORMATION-SYSTEM PROMIS;
ITEM RESPONSE THEORY; PLEXIFORM NEUROFIBROMAS; INTERFERENCE INDEX;
CHILDREN; TYPE-1; HEALTH; VALIDATION
AB Objective: Tumors and other disease complications of neurofibromatosis (NF) can cause pain and negatively affect physical functioning. To document the clinical benefit of treatment in NF trials targeting these manifestations, patient-reported outcomes (PROs) assessing pain and physical functioning should be included as study endpoints. Currently, there is no consensus on the selection and use of such measures in the NF population. This article presents the recommendations of the PRO group of the Response Evaluation in Neurofibromatosis and Schwannomatosis (REiNS) International Collaboration for assessing the domains of pain and physical functioning for NF clinical trials.
Methods: The REiNS PRO group reviewed and rated existing PRO measures assessing pain intensity, pain interference, and physical functioning using their systematic method. Final recommendations are based primarily on 4 main criteria: patient characteristics, item content, psychometric properties, and feasibility for clinical trials.
Results: The REiNS PRO group chose the Numeric Rating Scale-11 (>= 8 years) to assess pain intensity, the Pain Interference Index (6-24 years) and the Patient-Reported Outcome Measurement Information System (PROMIS) Pain Interference Scale (>= 18 years) to evaluate pain interference, and the PROMIS Physical Functioning Scale to measure upper extremity function and mobility (>= 5 years) for NF clinical trials.
Conclusions: The REiNS Collaboration currently recommends these PRO measures to assess the domains of pain and physical functioning for NF clinical trials; however, further research is needed to evaluate their use in individuals with NF. A final consensus recommendation for the pain interference measure will be disseminated in a future publication based on findings from additional published research.
C1 [Wolters, Pamela L.; Martin, Staci; Baldwin, Andrea] NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA.
[Merker, Vanessa L.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
[Merker, Vanessa L.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA.
[Tonsgard, James H.] Univ Chicago, Pritzker Sch Med, Chicago, IL 60637 USA.
[Solomon, Sondra E.] Univ Vermont, Dept Psychol Sci, Burlington, VT 05405 USA.
[Bergner, Amanda L.] Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21218 USA.
[Bergner, Amanda L.] Johns Hopkins Univ, Dept Genet, Baltimore, MD USA.
[Walsh, Karin] Childrens Natl Hlth Syst, Washington, DC USA.
[Walsh, Karin] George Washington Sch Med, Washington, DC USA.
[Thompson, Heather L.] Calif State Univ Sacramento, Dept Speech Pathol & Audiol, Sacramento, CA 95819 USA.
[Gardner, Kathy L.] Vet Adm Pittsburgh Healthcare Syst, Pittsburgh, PA USA.
[Gardner, Kathy L.] Univ Pittsburgh, Pittsburgh, PA 15260 USA.
[Hingtgen, Cynthia M.] Michigan State Univ, Dept Clin Neurosci, Spectrum Hlth Med Grp, E Lansing, MI 48824 USA.
[Hingtgen, Cynthia M.] Michigan State Univ, Coll Human Med, E Lansing, MI 48824 USA.
[Schorry, Elizabeth] Cincinnati Childrens Hosp, Div Human Genet, Cincinnati, OH USA.
[Dudley, William N.] Univ N Carolina, Sch Hlth & Human Sci, Dept Publ Hlth Educ, Greensboro, NC USA.
[Franklin, Barbara] Advocure NF2 Inc, Los Angeles, CA USA.
RP Wolters, PL (reprint author), NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA.
EM woltersp@mail.nih.gov
RI North, Kathryn/K-6476-2012;
OI North, Kathryn/0000-0003-0841-8009; Merker, Vanessa/0000-0002-4542-5227;
Evans, Gareth/0000-0002-8482-5784
FU NICHD NIH HHS [U54 HD090255]
NR 44
TC 2
Z9 2
U1 2
U2 2
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 AUG 16
PY 2016
VL 87
SU 1
BP S4
EP S12
DI 10.1212/WNL.0000000000002927
PG 9
WC Clinical Neurology
SC Neurosciences & Neurology
GA DU6MD
UT WOS:000382328100002
PM 27527648
ER
PT J
AU Rosario, AM
Perez-Stable, EJ
AF Rosario, Adelaida M.
Perez-Stable, Eliseo J.
TI Making Neighborhoods Good for Your Health
SO CIRCULATION
LA English
DT Editorial Material
DE Editorials; atherosclerosis; cardiovascular diseases; health status
disparities; outcome assessment (health care); residence characteristics
ID UNITED-STATES; ATHEROSCLEROSIS; ENVIRONMENT; IMPACT; COUNTY
C1 [Rosario, Adelaida M.] Natl Inst Minor Hlth & Hlth Dispar, Div Sci Programs, NIH, Bethesda, MD USA.
[Perez-Stable, Eliseo J.] Natl Inst Minor Hlth & Hlth Dispar, Off Director, NIH, Bethesda, MD USA.
RP Perez-Stable, EJ (reprint author), 6707 Democracy Blvd,Suite 800, Bethesda, MD 20892 USA.
EM eliseo.perez-stable@nih.gov
NR 14
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 0009-7322
EI 1524-4539
J9 CIRCULATION
JI Circulation
PD AUG 16
PY 2016
VL 134
IS 7
BP 514
EP 516
DI 10.1161/CIRCULATIONAHA.116.024158
PG 3
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA DU5XC
UT WOS:000382286000006
PM 27528646
ER
PT J
AU Simon, R
AF Simon, Richard
TI Genomic Alteration-Driven Clinical Trial Designs in Oncology
SO ANNALS OF INTERNAL MEDICINE
LA English
DT Article
ID PHASE-II TRIALS; LUNG-CANCER; VEMURAFENIB; THERAPY; PARADIGM; MEDICINE
AB The established molecular heterogeneity of human cancers necessitates the development of new paradigms to serve as a reliable basis for precision medicine. The assumptions underlying some of the conventional approaches to clinical trial design and analysis are no longer appropriate because of the molecular heterogeneity of tumors of a given primary site. This article reviews some clinical trial designs that have been actively applied in the codevelopment of therapeutics and predictive biomarkers to inform their use in oncology. These include the enrichment design, the basket design, and the umbrella design. Oncology leads most other therapeutic areas in development of personalized or precision medicine. Personalized or precision medicine is practiced daily in oncology on the basis of tumor genomics and may evolve in other therapeutic areas as it has in oncology, rather than according to inherited polymorphisms as so often imagined. Consequently, some of the clinical trial designs described here may serve as a possible blueprint for therapeutic development in fields other than oncology.
C1 [Simon, Richard] NCI, Rockville, MD 20892 USA.
RP Simon, R (reprint author), NCI, Div Canc Treatment & Diag, Biometr Res Program, 9609 Med Ctr Dr, Rockville, MD 20892 USA.
EM rsimon@nih.gov
NR 27
TC 1
Z9 1
U1 2
U2 4
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 AUG 16
PY 2016
VL 165
IS 4
BP 270
EP U114
DI 10.7326/M15-2413
PG 10
WC Medicine, General & Internal
SC General & Internal Medicine
GA DT1UI
UT WOS:000381267200016
PM 27214515
ER
PT J
AU Chertow, DS
Nath, A
Suffredini, AF
Danner, RL
Reich, DS
Bishop, RJ
Childs, RW
Arai, AE
Palmore, TN
Lane, HC
Fauci, AS
Davey, RT
AF Chertow, Daniel S.
Nath, Avindra
Suffredini, Anthony F.
Danner, Robert L.
Reich, Daniel S.
Bishop, Rachel J.
Childs, Richard W.
Arai, Andrew E.
Palmore, Tara N.
Lane, H. Clifford
Fauci, Anthony S.
Davey, Richard T.
TI Severe Meningoencephalitis in a Case of Ebola Virus Disease: A Case
Report
SO ANNALS OF INTERNAL MEDICINE
LA English
DT Letter
C1 [Chertow, Daniel S.; Suffredini, Anthony F.; Danner, Robert L.] NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA.
[Nath, Avindra; Reich, Daniel S.] NINDS, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
[Bishop, Rachel J.] NEI, NIH, Bethesda, MD 20892 USA.
[Childs, Richard W.; Arai, Andrew E.] NHLBI, NIH, Bldg 10, Bethesda, MD 20892 USA.
[Palmore, Tara N.] NIH, Hosp Epidemiol Serv, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA.
[Lane, H. Clifford; Fauci, Anthony S.; Davey, Richard T.] NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
RP Chertow, DS (reprint author), NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA.
FU Intramural NIH HHS [Z99 CL999999]
NR 6
TC 5
Z9 5
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 AUG 16
PY 2016
VL 165
IS 4
BP 301
EP 304
DI 10.7326/M15-3066
PG 4
WC Medicine, General & Internal
SC General & Internal Medicine
GA DT1UI
UT WOS:000381267200030
PM 27043004
ER
PT J
AU Crompton, PD
Pierce, SK
AF Crompton, Peter D.
Pierce, Susan K.
TI PD-L2 Elbows out PD-L1 to Rescue T Cell Immunity to Malaria
SO IMMUNITY
LA English
DT Editorial Material
AB How early interactions between innate and adaptive immune cells influence outcomes of acute infections is incompletely understood. In this issue of Immunity, Karunarathne et al. (2016) show that dendritic cells help CD4(+) T helper 1 cell immunity against malaria through PD-L2' s competition with PD-L1.
C1 [Crompton, Peter D.] NIAID, Malaria Infect Biol & Immun Unit, Immunogenet Lab, NIH, Rockville, MD 20852 USA.
[Pierce, Susan K.] NIAID, Lymphocyte Activat Sect, Immunogenet Lab, NIH, Rockville, MD 20852 USA.
RP Pierce, SK (reprint author), NIAID, Lymphocyte Activat Sect, Immunogenet Lab, NIH, Rockville, MD 20852 USA.
EM spierce@nih.gov
RI Crompton, Peter/N-1130-2016
NR 10
TC 0
Z9 0
U1 4
U2 4
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 AUG 16
PY 2016
VL 45
IS 2
BP 231
EP 233
DI 10.1016/j.immuni.2016.08.001
PG 4
WC Immunology
SC Immunology
GA DU5QV
UT WOS:000382267300004
PM 27533008
ER
PT J
AU Hess, C
Kemper, C
AF Hess, Christoph
Kemper, Claudia
TI Complement-Mediated Regulation of Metabolism and Basic Cellular
Processes
SO IMMUNITY
LA English
DT Review
ID NLRP3 INFLAMMASOME ACTIVATION; ADIPOSE-TISSUE INFLAMMATION; TOLL-LIKE
RECEPTORS; CD4(+) T-CELLS; INSULIN-RESISTANCE; GLYCOLYTIC SWITCH;
INDUCED APOPTOSIS; HUMAN MONOCYTES; INDUCED INJURY; GLUCOSE-UPTAKE
AB Complement is well appreciated as a critical arm of innate immunity. It is required for the removal of invading pathogens and works by directly destroying them through the activation of innate and adaptive immune cells. However, complement activation and function is not confined to the extracellular space but also occurs within cells. Recent work indicates that complement activation regulates key metabolic pathways and thus can impact fundamental cellular processes, such as survival, proliferation, and autophagy. Newly identified functions of complement include a key role in shaping metabolic reprogramming, which underlies T cell effector differentiation, and a role as a nexus for interactions with other effector systems, in particular the inflammasome and Notch transcription-factor networks. This review focuses on the contributions of complement to basic processes of the cell, in particular the integration of complement with cellular metabolism and the potential implications in infection and other disease settings.
C1 [Hess, Christoph] Univ Basel, Dept Biomed, Immunobiol, 20 Hebelstr, CH-4031 Basel, Switzerland.
[Kemper, Claudia] Kings Coll London, Guys Hosp, Div Transplant Immunol & Mucosal Biol, Med Res Council,Ctr Transplantat, London SE1 9RT, England.
[Kemper, Claudia] NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA.
[Kemper, Claudia] NHLBI, Ctr Immunol, NIH, Bethesda, MD 20892 USA.
RP Hess, C (reprint author), Univ Basel, Dept Biomed, Immunobiol, 20 Hebelstr, CH-4031 Basel, Switzerland.; Kemper, C (reprint author), Kings Coll London, Guys Hosp, Div Transplant Immunol & Mucosal Biol, Med Res Council,Ctr Transplantat, London SE1 9RT, England.; Kemper, C (reprint author), NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA.; Kemper, C (reprint author), NHLBI, Ctr Immunol, NIH, Bethesda, MD 20892 USA.
EM chess@uhbs.ch; claudia.kemper@kcl.ac.uk
FU MRC Centre grant [MR/J006742/1]; EU-funded Innovative Medicines
Initiative BTCURE; Wellcome Trust Investigator Award; King's Bioscience
Institute at King's College London; National Institute for Health
Research (NIHR) Biomedical Research Centre based at Guy's and St Thomas'
NHS Foundation Trust; King's College London; Division of Intramural
Research of the National Heart, Lung, and Blood Institute at the NIH;
intramural research program of NIAID, NIH; Swiss National Science
Foundation [310030_154059, CRSII_160766]; Gebert-Ruf Foundation
[GER-058/14]; Swiss Cancer League [KFS-3773-08-2015]
FX Work in the Hess and Kemper laboratories is supported by MRC Centre
grant MR/J006742/1, an EU-funded Innovative Medicines Initiative BTCURE
(C.K.), a Wellcome Trust Investigator Award (C.K.), the King's
Bioscience Institute at King's College London (G.A.), the National
Institute for Health Research (NIHR) Biomedical Research Centre based at
Guy's and St Thomas' NHS Foundation Trust and King's College London, the
Division of Intramural Research of the National Heart, Lung, and Blood
Institute at the NIH, the intramural research program of NIAID, NIH, the
Swiss National Science Foundation (310030_154059 and CRSII_160766)
(C.H.), the Gebert-Ruf Foundation (GER-058/14), and the Swiss Cancer
League (KFS-3773-08-2015).
NR 150
TC 1
Z9 1
U1 16
U2 17
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 AUG 16
PY 2016
VL 45
IS 2
BP 240
EP 254
DI 10.1016/j.immuni.2016.08.003
PG 15
WC Immunology
SC Immunology
GA DU5QV
UT WOS:000382267300008
PM 27533012
ER
PT J
AU Krishnamurty, AT
Thouvenel, CD
Portugal, S
Keitany, GJ
Kim, KS
Holder, A
Crompton, PD
Rawlings, DJ
Pepper, M
AF Krishnamurty, Akshay T.
Thouvenel, Christopher D.
Portugal, Silvia
Keitany, Gladys J.
Kim, Karen S.
Holder, Anthony
Crompton, Peter D.
Rawlings, David J.
Pepper, Marion
TI Somatically Hypermutated Plasmodium-Specific IgM(+) Memory B Cells Are
Rapid, Plastic, Early Responders upon Malaria Rechallenge
SO IMMUNITY
LA English
DT Article
ID MEROZOITE SURFACE PROTEIN-1; CD4(+) T-CELLS; PLASMA-CELLS; IMMUNOLOGICAL
MEMORY; PARASITE DEVELOPMENT; IMMUNE-RESPONSES; ANTIBODY-LEVELS;
IN-VITRO; FALCIPARUM; ANTIGEN
AB Humoral immunity consists of pre-existing antibodies expressed by long-lived plasma cells and rapidly reactive memory B cells (MBC). Recent studies of MBC development and function after protein immunization have uncovered significant MBC heterogeneity. To clarify functional roles for distinct MBC subsets during malaria infection, we generated tetramers that identify Plasmodium-specific MBCs in both humans and mice. Long-lived murine Plasmodium-specific MBCs consisted of three populations: somatically hypermutated immunoglobulin M+ (IgM +) and IgG(+) MBC subsets and an unmutated IgD(+) MBC population. Rechallenge experiments revealed that high affinity, somatically hypermutated Plasmodium-specific IgM(+) MBCs proliferated and gave rise to antibody-secreting cells that dominated the early secondary response to parasite rechallenge. IgM (+) MBCs also gave rise to T cell-dependent IgM(+) and IgG(+) B220(+) CD138(+) plasmablasts or T cell-independent B220-CD138(+) IgM(+) plasma cells. Thus, even in competition with IgG(+) MBCs, IgM(+) MBCs are rapid, plastic, early responders to a secondary Plasmodium rechallenge and should be targeted by vaccine strategies.
C1 [Krishnamurty, Akshay T.; Keitany, Gladys J.; Kim, Karen S.; Rawlings, David J.; Pepper, Marion] Univ Washington, Dept Immunol, Sch Med, Seattle, WA 98109 USA.
[Thouvenel, Christopher D.; Rawlings, David J.] Seattle Childrens Res Inst, Ctr Immun & Immunotherapies, Seattle, WA 98101 USA.
[Portugal, Silvia; Crompton, Peter D.] NIAID, Immunogenet Lab, NIH, Rockville, MD 20892 USA.
[Holder, Anthony] Francis Crick Inst, Mill Hill Lab, Ridgeway,Mill Hill, London NW7 1AA, England.
RP Pepper, M (reprint author), Univ Washington, Dept Immunol, Sch Med, Seattle, WA 98109 USA.
EM mpepper@uw.edu
RI Holder, Anthony/A-7554-2013; Crompton, Peter/N-1130-2016
OI Holder, Anthony/0000-0002-8490-6058;
FU NIH [T32-AI10667701]; [R01AI108626-01A-A87299]
FX We thank Dr. J. Langhorne and D. Perez-Mazliah for providing recombinant
MSP1 constructs and technical assistance, Dr. J. Rayner for providing P.
falciparum AMA1 protein, and Drs. M. Bevan and B. Hondowicz for
reviewing the manuscript and providing valuable discussion. We also
thank Drs. O. Doumbo and B. Traore and the residents of Kambila, Mali,
for helping acquire human PBMC samples. This work was supported by
grants to M.P. (NIH R01AI108626-01A-A87299), A.T.K. (NIH
T32-AI10667701), D.J.R. (Seattle Children's Research Institute, Center
for Immunity and Immunotherapies [CIIT]; the CIIT, Program for Cell and
Gene Therapy; and the Benaroya Family Gift Fund) and P.D.C. (NIH,
Division of Intramural Research, National Institute of Allergy and
Infectious Diseases).
NR 57
TC 1
Z9 1
U1 3
U2 5
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 AUG 16
PY 2016
VL 45
IS 2
BP 402
EP 414
DI 10.1016/j.immuni.2016.06.014
PG 13
WC Immunology
SC Immunology
GA DU5QV
UT WOS:000382267300020
PM 27473412
ER
PT J
AU Rosenberg, HF
Druey, KM
AF Rosenberg, Helene F.
Druey, Kirk M.
TI Eosinophils, galectins, and a reason to breathe
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Editorial Material
ID GLYCAN INTERACTIONS; MURINE MODEL; ASTHMA; INFLAMMATION;
HYPERRESPONSIVENESS; MEPOLIZUMAB; PROTEIN; HEALTH; LECTIN; CELLS
C1 [Rosenberg, Helene F.] NIH, Inflammat Immunobiol Sect, Lab Allerg Dis, Bethesda, MD 20892 USA.
[Druey, Kirk M.] NIH, Mol Signal Transduct Sect, Lab Allerg Dis, Bethesda, MD 20892 USA.
RP Rosenberg, HF (reprint author), NIH, Inflammat Immunobiol Sect, Lab Allerg Dis, Bethesda, MD 20892 USA.
EM hrosenberg@niaid.nih.gov
FU NIAID NIH HHS [Z01 AI000746, Z01 AI000939, Z01 AI000941, Z01 AI000943]
NR 25
TC 0
Z9 0
U1 0
U2 0
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 AUG 16
PY 2016
VL 113
IS 33
BP 9139
EP 9141
DI 10.1073/pnas.1610644113
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DT3RS
UT WOS:000381399200030
PM 27496328
ER
PT J
AU Nolte-'t Hoen, E
Cremer, T
Gallo, RC
Margolis, LB
AF Nolte-'t Hoen, Esther
Cremer, Tom
Gallo, Robert C.
Margolis, Leonid B.
TI Extracellular vesicles and viruses: Are they close relatives?
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE extracellular vesicles; exosomes; viruses; defective viruses; infection
ID EXOSOMAL TRANSFER; DENDRITIC CELLS; RECIPIENT CELLS; INNATE IMMUNITY;
HIV-1; INFECTION; RNA; SECRETION; MICROVESICLES; MECHANISM
AB Extracellular vesicles (EVs) released by various cells are small phospholipid membrane-enclosed entities that can carry miRNA. They are now central to research in many fields of biology because they seem to constitute a new system of cell-cell communication. Physical and chemical characteristics of many EVs, as well as their biogenesis pathways, resemble those of retroviruses. Moreover, EVs generated by virus-infected cells can incorporate viral proteins and fragments of viral RNA, being thus indistinguishable from defective (noninfectious) retroviruses. EVs, depending on the proteins and genetic material incorporated in them, play a significant role in viral infection, both facilitating and suppressing it. Deciphering the mechanisms of EV-cell interactions may facilitate the design of EVs that inhibit viral infection and can be used as vehicles for targeted drug delivery.
C1 [Nolte-'t Hoen, Esther; Cremer, Tom] Univ Utrecht, Fac Vet Med, Dept Biochem & Cell Biol, NL-3584 CM Utrecht, Netherlands.
[Gallo, Robert C.] Univ Maryland, Inst Human Virol, Baltimore, MD 21201 USA.
[Margolis, Leonid B.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Intercellular Interact, NIH, Bethesda, MD 20892 USA.
RP Gallo, RC (reprint author), Univ Maryland, Inst Human Virol, Baltimore, MD 21201 USA.
EM rgallo@ihv.umaryland.edu
FU European Research Council (ERC) under the European Union's Seventh
Framework Programme (FP)/ERC grant [337581]; National Institute of Child
Health and Human Development/NIH Intramural Program; Gates Foundation;
National Institute of Allergy and Infectious Diseases; University of
Maryland School of Medicine
FX E.N.-t.H. receives funding from the European Research Council (ERC)
under the European Union's Seventh Framework Programme
(FP/2007-2013)/ERC grant agreement 337581; the work of L.B.M. is funded
by the National Institute of Child Health and Human Development/NIH
Intramural Program; the work of R.C.G. is funded by the Gates
Foundation, the National Institute of Allergy and Infectious Diseases,
and the University of Maryland School of Medicine.
NR 63
TC 2
Z9 2
U1 14
U2 17
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 AUG 16
PY 2016
VL 113
IS 33
BP 9155
EP 9161
DI 10.1073/pnas.1605146113
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DT3RS
UT WOS:000381399200034
PM 27432966
ER
PT J
AU Salie, ZL
Kirby, KA
Michailidis, E
Marchand, B
Singh, K
Rohan, LC
Kodama, EN
Mitsuya, H
Parniak, MA
Sarafianos, SG
AF Salie, Zhe Li
Kirby, Karen A.
Michailidis, Eleftherios
Marchand, Bruno
Singh, Kamalendra
Rohan, Lisa C.
Kodama, Eiichi N.
Mitsuya, Hiroaki
Parniak, Michael A.
Sarafianos, Stefan G.
TI Structural basis of HIV inhibition by translocation-defective RT
inhibitor 4 '-ethynyl-2-fluoro-2 '-deoxyadenosine (EFdA)
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE EFdA; HIV-1 reverse transcriptase; inhibitors; NRTIs; X-ray
crystallography
ID REVERSE-TRANSCRIPTASE INHIBITOR; IMMUNODEFICIENCY-VIRUS TYPE-1;
HEPATITIS-B; DRUG-RESISTANCE; NUCLEOSIDE EFDA; POTENT; DNA; SOFOSBUVIR;
ENTECAVIR; SOFTWARE
AB 4'-Ethynyl-2-fluoro-2'-deoxyadenosine (EFdA) is the most potent nucleoside analog inhibitor of HIV reverse transcriptase (RT). It retains a 3'-OH yet acts as a chain-terminating agent by diminishing translocation from the pretranslocation nucleotide-binding site (N site) to the posttranslocation primer-binding site (P site). Also, facile misincorporation of EFdA-monophosphate (MP) results in difficult-to-extend mismatched primers. To understand the high potency and unusual inhibition mechanism of EFdA, we solved RT crystal structures (resolutions from 2.4 to 2.9 angstrom) that include inhibition intermediates (i) before inhibitor incorporation (catalytic complex, RT/DNA/EFdA-triphosphate), (ii) after incorporation of EFdA-MP followed by dT-MP (RT/DNA(EFdA-MPP center dot dT-MPN)), or (iii) after incorporation of two EFdA-MPs (RT/DNA(EFdA-MPP center dot EFdA-MPN)); (iv) the latter was also solved with EFdA-MP mismatched at the N site (RT/DNA(EFdA-MPP center dot EFdA-MP*N)). We report that the inhibition mechanism and potency of EFdA stem from interactions of its 4'-ethynyl at a previously unexploited conserved hydrophobic pocket in the polymerase active site. The high resolution of the catalytic complex structure revealed a network of ordered water molecules at the polymerase active site that stabilize enzyme interactions with nucleotide and DNA substrates. Finally, decreased translocation results from favorable interactions of primer-terminating EFdA-MP at the pretranslocation site and unfavorable posttranslocation interactions that lead to observed localized primer distortions.
C1 [Salie, Zhe Li; Sarafianos, Stefan G.] Univ Missouri, Dept Biochem, CS Bond Life Sci Ctr, Columbia, MO 65211 USA.
[Kirby, Karen A.; Michailidis, Eleftherios; Marchand, Bruno; Singh, Kamalendra; Sarafianos, Stefan G.] Univ Missouri, Sch Med, Dept Mol Microbiol & Immunol, CS Bond Life Sci Ctr, Columbia, MO 65211 USA.
[Rohan, Lisa C.] Univ Pittsburgh, Dept Pharmaceut Sci, Pittsburgh, PA 15261 USA.
[Rohan, Lisa C.] Univ Pittsburgh, Magee Womens Res Inst, Pittsburgh, PA 15213 USA.
[Kodama, Eiichi N.] Tohoku Univ, Div Infect Dis, Sendai, Miyagi 9808575, Japan.
[Kodama, Eiichi N.] Tohoku Med Megabank Org, Sendai, Miyagi 9808575, Japan.
[Mitsuya, Hiroaki] NCI, Expt Retrovirol Sect, HIV & AIDS Malignancy Branch, NIH, Bethesda, MD 20892 USA.
[Mitsuya, Hiroaki] Kumamoto Univ, Grad Sch Med Sci, Dept Infect Dis, Kumamoto 8608556, Japan.
[Mitsuya, Hiroaki] Kumamoto Univ, Grad Sch Med Sci, Dept Hematol, Kumamoto 8608556, Japan.
[Mitsuya, Hiroaki] Natl Ctr Global Hlth & Med, Res Inst, Tokyo 1628655, Japan.
[Mitsuya, Hiroaki] Natl Ctr Global Hlth & Med, Ctr Clin Sci, Tokyo 1628655, Japan.
[Parniak, Michael A.] Univ Pittsburgh, Sch Med, Dept Microbiol & Mol Genet, Pittsburgh, PA 15219 USA.
RP Sarafianos, SG (reprint author), Univ Missouri, Dept Biochem, CS Bond Life Sci Ctr, Columbia, MO 65211 USA.; Sarafianos, SG (reprint author), Univ Missouri, Sch Med, Dept Mol Microbiol & Immunol, CS Bond Life Sci Ctr, Columbia, MO 65211 USA.
EM sarafianoss@missouri.edu
RI Kodama, Eiichi /C-4032-2009;
OI Kodama, Eiichi /0000-0002-6622-2752; Li, Zhe/0000-0003-2063-1013;
Sarafianos, Stefan G/0000-0002-5840-154X; Kirby, Karen
A./0000-0003-2468-4796
FU Office of Science, Office of Basic Energy Sciences, of the US Department
of Energy (DOE) [DE-AC02-05CH11231]; US DOE [DE-AC02-06CH11357];
National Institutes of Health [AI076119, AI099284, AI100890, AI120860,
GM103368, GM118012]; Mizzou Advantage; Trail to a Cure
FX We thank Jay Nix of Advanced Light Source beamline 4.2.2 for support.
The ALS is supported by the Director, Office of Science, Office of Basic
Energy Sciences, of the US Department of Energy (DOE) under Contract
DE-AC02-05CH11231. We also acknowledge the Advanced Photon Source. Use
of the Advanced Photon Source, an Office of Science User Facility
operated for the US DOE Office of Science by Argonne National
Laboratory, was supported by the US DOE under Contract
DE-AC02-06CH11357. This work was supported in part by grants from the
National Institutes of Health (AI076119, AI099284, AI100890, AI120860,
GM103368, and GM118012), Mizzou Advantage, and Trail to a Cure.
NR 26
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U1 2
U2 2
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 AUG 16
PY 2016
VL 113
IS 33
BP 9274
EP 9279
DI 10.1073/pnas.1605223113
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DT3RS
UT WOS:000381399200054
PM 27489345
ER
PT J
AU Levine, ME
Lu, AT
Chen, BH
Hernandez, DG
Singleton, AB
Ferrucci, L
Bandinelli, S
Salfati, E
Manson, JE
Quach, A
Kusters, CDJ
Kuh, D
Wong, A
Teschendorff, AE
Widschwendter, M
Ritz, BR
Absher, D
Assimes, TL
Horvath, S
AF Levine, Morgan E.
Lu, Ake T.
Chen, Brian H.
Hernandez, Dena G.
Singleton, Andrew B.
Ferrucci, Luigi
Bandinelli, Stefania
Salfati, Elias
Manson, JoAnn E.
Quach, Austin
Kusters, Cynthia D. J.
Kuh, Diana
Wong, Andrew
Teschendorff, Andrew E.
Widschwendter, Martin
Ritz, Beate R.
Absher, Devin
Assimes, Themistocles L.
Horvath, Steve
TI Menopause accelerates biological aging
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE menopause; DNA methylation; aging; WHI; epigenetic clock
ID BRITISH BIRTH COHORT; DNA METHYLATION AGE; NATURAL MENOPAUSE; EPIGENETIC
AGE; PARKINSONS-DISEASE; PREFRONTAL CORTEX; LIFE-SPAN; BLOOD; MORTALITY;
EPIDEMIOLOGY
AB Although epigenetic processes have been linked to aging and disease in other systems, it is not yet known whether they relate to reproductive aging. Recently, we developed a highly accurate epigenetic biomarker of age (known as the "epigenetic clock"), which is based on DNA methylation levels. Here we carry out an epigenetic clock analysis of blood, saliva, and buccal epithelium using data from four large studies: the Women's Health Initiative (n = 1,864); Invec-chiare nel Chianti (n = 200); Parkinson's disease, Environment, and Genes (n = 256); and the United Kingdom Medical Research Council National Survey of Health and Development (n = 790). We find that increased epigenetic age acceleration in blood is significantly associated with earlier menopause (P = 0.00091), bilateral oophorectomy (P = 0.0018), and a longer time since menopause (P = 0.017). Conversely, epigenetic age acceleration in buccal epithelium and saliva do not relate to age at menopause; however, a higher epigenetic age in saliva is exhibited in women who undergo bilateral oophorectomy (P = 0.0079), while a lower epigenetic age in buccal epithelium was found for women who underwent menopausal hormone therapy (P = 0.00078). Using genetic data, we find evidence of coheritability between age at menopause and epigenetic age acceleration in blood. Using Mendelian randomization analysis, we find that two SNPs that are highly associated with age at menopause exhibit a significant association with epigenetic age acceleration. Overall, our Mendelian randomization approach and other lines of evidence suggest that menopause accelerates epigenetic aging of blood, but mechanistic studies will be needed to dissect cause-and-effect relationships further.
C1 [Levine, Morgan E.; Lu, Ake T.; Quach, Austin; Horvath, Steve] Univ Calif Los Angeles, David Geffen Sch Med, Dept Human Genet, Los Angeles, CA 90095 USA.
[Levine, Morgan E.] Univ Calif Los Angeles, Ctr Neurobehav Genet, Los Angeles, CA 90095 USA.
[Chen, Brian H.; Ferrucci, Luigi] NIA, Longitudinal Studies Sect, Translat Gerontol Branch, Intramural Res Program,NIH, Bethesda, MD 20892 USA.
[Hernandez, Dena G.; Singleton, Andrew B.] NIA, Lab Neurogenet, Intramural Res Program, NIH, Bethesda, MD 20892 USA.
[Bandinelli, Stefania] Azienda Sanit Firenze, Geriatr Unit, I-50100 Florence, Italy.
[Salfati, Elias; Assimes, Themistocles L.] Stanford Univ, Sch Med, Dept Med, Stanford, CA 94305 USA.
[Manson, JoAnn E.] Harvard Med Sch, Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA.
[Kusters, Cynthia D. J.; Ritz, Beate R.] Univ Calif Los Angeles, Sch Publ Hlth, Dept Epidemiol, Los Angeles, CA 90095 USA.
[Kuh, Diana; Wong, Andrew] UCL, Unit Lifelong Hlth & Ageing, Med Res Council, London WC1B 5JU, England.
[Teschendorff, Andrew E.; Widschwendter, Martin] UCL, Dept Womens Canc, London WC1 6BT, England.
[Teschendorff, Andrew E.] UCL, Inst Canc, London WC1 6BT, England.
[Teschendorff, Andrew E.] UCL, Inst Canc, Stat Genom Grp, London WC1E 6DD, England.
[Teschendorff, Andrew E.] Chinese Acad Sci, Shanghai Inst Biol, Chinese Acad Sci Max Planck Soc Partner Inst Comp, Key Lab Computat Biol, Shanghai 200031, Peoples R China.
[Absher, Devin] HudsonAlpha Inst Biotechnol, Huntsville, AL 35806 USA.
[Horvath, Steve] Univ Calif Los Angeles, Fielding Sch Publ Hlth, Dept Biostat, Los Angeles, CA 90095 USA.
RP Horvath, S (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Human Genet, Los Angeles, CA 90095 USA.; Horvath, S (reprint author), Univ Calif Los Angeles, Fielding Sch Publ Hlth, Dept Biostat, Los Angeles, CA 90095 USA.
EM shorvath@mednet.ucla.edu
RI Assimes, Themistocles/D-9696-2015; Wong, Andrew/M-8899-2016
OI Assimes, Themistocles/0000-0003-2349-0009; Wong,
Andrew/0000-0003-2079-4779
FU NIH/NHLBI Grant [60442456 BAA23]; NIH/National Institute on Aging Grant
[1U34AG051425-01]; NIH/National Institute of Neurological Disorders and
Stroke Grant [T32NS048004]; NHLBI of the NIH, US Department of Health
and Human Services [HHSN268201100046C, HHSN268201100001C,
HHSN268201100002C, HHSN268201100003C, HHSN268201100004C,
HHSN271201100004C]; Eve Appeal; Department of Health National Institute
for Health Research Biomedical Research Centres funding scheme; UK
Medical Research Council Grant [MC_UU_12019/1]; NIH/National Institute
of Environmental Health Sciences Grants [R21-ES024356, R01-ES10544]
FX This study was supported by NIH/NHLBI Grant 60442456 BAA23 (to T.L.A.,
D.A., and S.H.), NIH/National Institute on Aging Grant 1U34AG051425-01
(to S.H.), and NIH/National Institute of Neurological Disorders and
Stroke Grant T32NS048004 (to M.E.L.). The WHI program is funded by the
NHLBI of the NIH, US Department of Health and Human Services through
Contracts HHSN268201100046C, HHSN268201100001C, HHSN268201100002C,
HHSN268201100003C, HHSN268201100004C, and HHSN271201100004C. Part of
this work was funded by the Eve Appeal (https://www.eveappeal.org.uk/)
and was done at University College London Hospital/University College
London, which received a proportion of its funding from the Department
of Health National Institute for Health Research Biomedical Research
Centres funding scheme (M.W.). The NSHD is funded by UK Medical Research
Council Grant MC_UU_12019/1. The PEG study was funded by NIH/National
Institute of Environmental Health Sciences Grants R21-ES024356 (to S.H.
and B.R.R.) and R01-ES10544 (to B.R.R.).
NR 47
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Z9 7
U1 11
U2 15
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 AUG 16
PY 2016
VL 113
IS 33
BP 9327
EP 9332
DI 10.1073/pnas.1604558113
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DT3RS
UT WOS:000381399200063
PM 27457926
ER
PT J
AU Yim, KH
Prince, TL
Qu, SW
Bai, F
Jennings, PA
Onuchic, JN
Theodorakis, EA
Neckers, L
AF Yim, Kendrick H.
Prince, Thomas L.
Qu, Shiwei
Bai, Fang
Jennings, Patricia A.
Onuchic, Jose N.
Theodorakis, Emmanuel A.
Neckers, Leonard
TI Gambogic acid identifies an isoform-specific druggable pocket in the
middle domain of Hsp90 beta
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE molecular chaperone; heat-shock protein 90; isoform-specific inhibitor;
molecular docking; caged xanthone
ID SHOCK-PROTEIN 90; POTENT ANTITUMOR-ACTIVITY; CAGED GARCINIA XANTHONES;
MOLECULAR CHAPERONE; BINDING-SITE; CANCER-CELLS; DOWN-REGULATION; ATOMIC
CHARGES; BREAST-CANCER; TUMOR-GROWTH
AB Because of their importance in maintaining protein homeostasis, molecular chaperones, including heat-shock protein 90 (Hsp90), represent attractive drug targets. Although a number of Hsp90 inhibitors are in preclinical/clinical development, none strongly differentiate between constitutively expressed Hsp90 beta and stress-induced Hsp90 alpha, the two cytosolic paralogs of this molecular chaperone. Thus, the importance of inhibiting one or the other paralog in different disease states remains unknown. We show that the natural product, gambogic acid (GBA), binds selectively to a site in the middle domain of Hsp90 beta, identifying GBA as an Hsp90 beta-specific Hsp90 inhibitor. Furthermore, using computational and medicinal chemistry, we identified a GBA analog, referred to as DAP-19, which binds potently and selectively to Hsp90 beta. Because of its unprecedented selectivity for Hsp90 beta among all Hsp90 paralogs, GBA thus provides a new chemical tool to study the unique biological role of this abundantly expressed molecular chaperone in health and disease.
C1 [Yim, Kendrick H.; Prince, Thomas L.; Neckers, Leonard] NCI, Urol Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Qu, Shiwei; Jennings, Patricia A.; Theodorakis, Emmanuel A.] Univ Calif San Diego, Dept Chem & Biochem, La Jolla, CA 92093 USA.
[Bai, Fang; Onuchic, Jose N.] Rice Univ, Ctr Theoret Biol Phys, Houston, TX 77005 USA.
[Onuchic, Jose N.] Rice Univ, Dept Phys & Astron, Houston, TX 77005 USA.
[Onuchic, Jose N.] Rice Univ, Dept Chem, Houston, TX 77005 USA.
[Onuchic, Jose N.] Rice Univ, Dept Biosci, Houston, TX 77005 USA.
RP Neckers, L (reprint author), NCI, Urol Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM neckersl@mail.nih.gov
FU Intramural Research Program, Center for Cancer Research, National Cancer
Institute Grant [Z01 SC010074-12]; National Institutes of Health Grants
[CA 133002, GM101467]; Cancer Research Coordinating Committee
[CRC-15-380737]; National Science Foundation [PHY-1427654, MCB-1214457];
Cancer Prevention and Research Institute of Texas; Welch Foundation
Grant [C-1792]
FX This work was supported in part by the Intramural Research Program,
Center for Cancer Research, National Cancer Institute Grant Z01
SC010074-12 (to L.N.); National Institutes of Health Grants CA 133002
(to E.A.T.) and GM101467 (to P.A.J.); and a grant from the Cancer
Research Coordinating Committee (CRC-15-380737) (to E.A.T.). Work at the
Center for Theoretical Biological Physics was sponsored by the National
Science Foundation (Grants PHY-1427654 and MCB-1214457) and the Cancer
Prevention and Research Institute of Texas. F.B. was also supported by
Welch Foundation Grant C-1792.
NR 66
TC 2
Z9 2
U1 11
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 AUG 16
PY 2016
VL 113
IS 33
BP E4801
EP E4809
DI 10.1073/pnas.1606655113
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DT3RS
UT WOS:000381399200009
PM 27466407
ER
PT J
AU Warnick, EP
Dupuis, RJ
Piro, NA
Kassel, WS
Nataro, C
AF Warnick, Eugene P.
Dupuis, Ryan J.
Piro, Nicholas A.
Kassel, W. Scott
Nataro, Chip
TI Compounds containing weak, non-covalent interactions to the metal in the
backbone of 1,1 '-bis(phosphino)metallocene ligands
SO POLYHEDRON
LA English
DT Article
DE Halide abstraction; Chloride-bridged dimer; Weak non-covalent
interaction; X-ray crystal structure; Cyclic voltammetry
ID SYMMETRICALLY DISUBSTITUTED FERROCENES; X-RAY STRUCTURES;
1,1'-BIS(DIPHENYLPHOSPHINO)FERROCENE DPPF; MOLECULAR-STRUCTURES;
CRYSTAL-STRUCTURE; ROOM-TEMPERATURE; COMPLEXES; PALLADIUM; CHEMISTRY;
PHOSPHINE
AB The reactions of Na[BArF] (BArF = tetrakis(3,5-bis(trifluoromethyl)phenyl)borate) with a series of [Pd(dpEMc)Cl-2] (dpEMc = 1,1'-bis(diphenylphosphino)ruthenocene (dppr), 1,1'-bis(diphenylphosphino)osmocene (dppo) or 1,1'-bis(diphenylarsino)ferrocene (dpaf)) compounds were examined. The reaction of Na[BArF] with [Pd(dppMc)Cl-2] (dppMc = dppr or dppo) resulted in the formation of the corresponding chloride-bridged dimers, [Pd(dppMc)(mu-Cl)](2)(2+), which were structurally characterized. However, these dimers appear to be unstable in CH2Cl2 and partially (Ru) or fully (Os) convert into the corresponding monomers, [Pd(dppMc)Cl](+), which are proposed to have a weak, non-covalent M-Pd (M = Ru or Os) interaction. Similar compounds, [Pd(dppo)PPh3](2+) and [Pt(dppMc)PPh3](2+) (M = Fe (1,1'-bis(diphenylphosphino)ferrocene (dppf)) or Os (dppo)), were also prepared and structurally characterized. These compound also exhibit weak, non-covalent M-Pd/Pt interactions. In addition, the electrochemical properties of these compounds were examined by cyclic voltammetry. (C) 2015 Elsevier Ltd. All rights reserved.
C1 [Warnick, Eugene P.; Dupuis, Ryan J.; Nataro, Chip] Dept Chem, Lafayette Coll, Easton, PA 18042 USA.
[Piro, Nicholas A.; Kassel, W. Scott] Villanova Univ, Dept Chem, Villanova, PA 19085 USA.
[Warnick, Eugene P.] NIH, Bethesda, MD 20892 USA.
RP Nataro, C (reprint author), Dept Chem, Lafayette Coll, Easton, PA 18042 USA.
EM nataroc@lafayette.edu
OI Nataro, Chip/0000-0003-0439-9218
FU Academic Research Committee at Lafayette College
FX E.P.W., R.J.D. and C.N. thank Kresge Foundation for the purchase of the
JEOL NMR, and the Academic Research Committee at Lafayette College for
funding EXCEL scholars.
NR 48
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 0277-5387
J9 POLYHEDRON
JI Polyhedron
PD AUG 16
PY 2016
VL 114
SI SI
BP 156
EP 164
DI 10.1016/j.poly.2015.11.025
PG 9
WC Chemistry, Inorganic & Nuclear; Crystallography
SC Chemistry; Crystallography
GA DQ9YE
UT WOS:000379564400023
ER
PT J
AU Ma, B
Xu, LY
Pan, XD
Sun, LX
Ding, JH
Xie, CS
Koliatsos, VE
Cai, HB
AF Ma, Bo
Xu, Leyan
Pan, Xiaodong
Sun, Lixin
Ding, Jinhui
Xie, Chengsong
Koliatsos, Vassilis E.
Cai, Huaibin
TI LRRK2 modulates microglial activity through regulation of chemokine
(C-X3-C) receptor 1-mediated signalling pathways
SO HUMAN MOLECULAR GENETICS
LA English
DT Article
ID PARKINSONS-DISEASE; FRACTALKINE RECEPTOR; CULTURED MICROGLIA;
ALPHA-SYNUCLEIN; MOUSE MODEL; KINASE; CELLS; ACTIVATION; CX3CL1;
PHOSPHORYLATION
AB Multiple missense mutations in Leucine-rich repeat kinase 2 (LRRK2) have been linked to Parkinson's disease (PD), the most common degenerative movement disorder. LRRK2 is expressed by both neurons and microglia, the residential immune cells in the brain. Increasing evidence supports a role of LRRK2 in modulating microglial activity, of which Lrrk2-null rodent microglia display less inflammatory response to endotoxin lipopolysaccharide (LPS). The underlying molecular mechanism, however, remains elusive. Chemokine (C-X3-C) receptor 1 (CX3CR1), predominantly expressed by microglia, suppresses microglial inflammation while promotes migration. Using whole-genome microarray screening, we found that Cx3cr1 mRNA levels were substantially higher in microglia derived from Lrrk2 knockout (Lrrk2(-/-)) mice. The total and cell surface levels of CX3CR1 proteins were also remarkably increased. In correlation with the enhanced CX3CR1 expression, Lrrk2-null microglia migrated faster and travelled longer distance toward the source of fractalkine (CX3CL1), an endogenous ligand of CX3CR1. To investigate the impact of CX3CR1 elevation in vivo, we compared LPS-induced inflammation in the striatum of Lrrk2(-/-) knockout mice with Cx3cr1 heterozygous and homozygous knockout background. We found that a complete loss of Cx3cr1 restored the responsiveness of Lrrk2(-/-) microglia to LPS stimulation. In conclusion, our findings reveal a previously unknown regulatory role for LRRK2 in CX3CR1 signalling and suggest that an increase of CX3CR1 activity contributes to the attenuated inflammatory responses in Lrrk2-null microglia.
C1 [Ma, Bo; Pan, Xiaodong; Sun, Lixin; Xie, Chengsong; Cai, Huaibin] NIA, Transgen Sect, Neurogenet Lab, NIH, Bldg 35,Room 1A112,MSC 3707,35 Convent Dr, Bethesda, MD 20892 USA.
[Xu, Leyan; Koliatsos, Vassilis E.] Johns Hopkins Univ, Sch Med, Dept Pathol, Div Neuropathol, Baltimore, MD 21205 USA.
[Ding, Jinhui] NIA, Bioinformat Core, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
[Ma, Bo] Univ Florida, Coll Med, Dept Anesthesiol, Ctr Translat Res Neurodegenerat Dis, 1275 Ctr Dr,Biomed Sci J448, Gainesville, FL 32610 USA.
[Pan, Xiaodong] Fujian Med Univ, Union Hosp, Dept Neurol, 29 Xinquan Rd, Fuzhou 350001, Peoples R China.
RP Cai, HB (reprint author), NIA, Transgen Sect, Neurogenet Lab, NIH, Bldg 35,Room 1A112,MSC 3707,35 Convent Dr, Bethesda, MD 20892 USA.
EM caih@mail.nih.gov
FU intramural research programs of the National Institutes of Health
(NIH)-National Institute on Aging [AG000928, AG000944]; National Natural
Science Grant of China [81571257]
FX This work was supported in part by the intramural research programs of
the National Institutes of Health (NIH)-National Institute on Aging
(Grants AG000928 and AG000944 to H.C.), and National Natural Science
Grant of China (No. 81571257 to XD P.).
NR 43
TC 1
Z9 1
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 AUG 15
PY 2016
VL 25
IS 16
BP 3515
EP 3523
DI 10.1093/hmg/ddw194
PG 9
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA EJ4IO
UT WOS:000393180400011
PM 27378696
ER
PT J
AU Permuth, JB
Pirie, A
Chen, YA
Lin, HY
Reid, BM
Chen, ZH
Monteiro, A
Dennis, J
Mendoza-Fandino, G
Anton-Culver, H
Bandera, EV
Bisogna, M
Brinton, L
Brooks-Wilson, A
Carney, ME
Chenevix-Trench, G
Cook, LS
Cramer, DW
Cunningham, JM
Cybulski, C
D'Aloisio, AA
Doherty, JA
Earp, M
Edwards, RP
Fridley, BL
Gayther, SA
Gentry-Maharaj, A
Goodman, MT
Gronwald, J
Hogdall, E
Iversen, ES
Jakubowska, A
Jensen, A
Karlan, BY
Kelemen, LE
Kjaer, SK
Kraft, P
Le, ND
Levine, DA
Lissowska, J
Lubinski, J
Matsuo, K
Menon, U
Modugno, R
Moysich, KB
Nakanishi, T
Ness, RB
Olson, S
Orlow, I
Pearce, CL
Pejovic, T
Poole, EM
Ramus, SJ
Rossing, MA
Sandler, DP
Shu, XO
Song, H
Taylor, JA
Teo, SH
Terry, KL
Thompson, PJ
Tworoger, SS
Webb, PM
Wentzensen, N
Wilkens, LR
Winham, S
Woo, YL
Wu, AH
Yang, H
Zheng, W
Ziogas, A
Phelan, CM
Schildkraut, JM
Berchuck, A
Goode, EL
Pharoah, PDP
Sellers, TA
AF Permuth, Jennifer B.
Pirie, Ailith
Chen, Y. Ann
Lin, Hui-Yi
Reid, Brett M.
Chen, Zhihua
Monteiro, Alvaro
Dennis, Joe
Mendoza-Fandino, Gustavo
Anton-Culver, Hoda
Bandera, Elisa V.
Bisogna, Maria
Brinton, Louise
Brooks-Wilson, Angela
Carney, Michael E.
Chenevix-Trench, Georgia
Cook, Linda S.
Cramer, Daniel W.
Cunningham, Julie M.
Cybulski, Cezary
D'Aloisio, Aimee A.
Doherty, Jennifer Anne
Earp, Madalene
Edwards, Robert P.
Fridley, Brooke L.
Gayther, Simon A.
Gentry-Maharaj, Aleksandra
Goodman, Marc T.
Gronwald, Jacek
Hogdall, Estrid
Iversen, Edwin S.
Jakubowska, Anna
Jensen, Allan
Karlan, Beth Y.
Kelemen, Linda E.
Kjaer, Suzanne K.
Kraft, Peter
Le, Nhu D.
Levine, Douglas A.
Lissowska, Jolanta
Lubinski, Jan
Matsuo, Keitaro
Menon, Usha
Modugno, Rosemary
Moysich, Kirsten B.
Nakanishi, Toru
Ness, Roberta B.
Olson, Sara
Orlow, Irene
Pearce, Celeste L.
Pejovic, Tanja
Poole, Elizabeth M.
Ramus, Susan J.
Rossing, Mary Anne
Sandler, Dale P.
Shu, Xiao-Ou
Song, Honglin
Taylor, Jack A.
Teo, Soo-Hwang
Terry, Kathryn L.
Thompson, Pamela J.
Tworoger, Shelley S.
Webb, Penelope M.
Wentzensen, Nicolas
Wilkens, Lynne R.
Winham, Stacey
Woo, Yin-Ling
Wu, Anna H.
Yang, Hannah
Zheng, Wei
Ziogas, Argyrios
Phelan, Catherine M.
Schildkraut, Joellen M.
Berchuck, Andrew
Goode, Ellen L.
Pharoah, Paul D. P.
Sellers, Thomas A.
CA AOCS Study Grp
Australian Canc Study Ovarian Canc
Ovarian Canc Assoc Consortium
TI Exome genotyping arrays to identify rare and low frequency variants
associated with epithelial ovarian cancer risk
SO HUMAN MOLECULAR GENETICS
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; MAXIMUM-LIKELIHOOD TEST; SUSCEPTIBILITY LOCI;
GENE-EXPRESSION; BREAST-CANCER; CUSHINGS-SYNDROME; PROSTATE-CANCER;
COMPLEX DISEASE; IDENTIFICATION; CARCINOMA
AB Rare and low frequency variants are not well covered in most germline genotyping arrays and are understudied in relation to epithelial ovarian cancer (EOC) risk. To address this gap, we used genotyping arrays targeting rarer protein-coding variation in 8,165 EOC cases and 11,619 controls from the international Ovarian Cancer Association Consortium (OCAC). Pooled association analyses were conducted at the variant and gene level for 98,543 variants directly genotyped through two exome genotyping projects. Only common variants that represent or are in strong linkage disequilibrium (LD) with previously-identified signals at established loci reached traditional thresholds for exome-wide significance (P < 5.0 x 10(-7)). One of the most significant signals (P-all histologies = 1.01 x 10(-13);P-serous = 3.54 x 10(-14)) occurred at 3q25.31 for rs62273959, a missense variant mapping to the LEKR1 gene that is in LD (r(2) = 0.90) with a previously identified 'best hit' (rs7651446) mapping to an intron of TIPARP. Suggestive associations (5.0 x 10(-5) > P >= 5.0 x10(-7)) were detected for rare and low-frequency variants at 16 novel loci. Four rare missense variants were identified (ACTBL2 rs73757391 (5q11.2), BTD rs200337373 (3p25.1), KRT13 rs150321809 (17q21.2) and MC2R rs104894658 (18p11.21)), but only MC2R rs104894668 had a large effect size (OR = 9.66). Genes most strongly associated with EOC risk included ACTBL2 (P-AML = 3.23 x 10(-5); PSKAT-o = 9.23 x 10(-4)) and KRT13 (PAML = 1.67 x 10(-4); PSKAT-o = 1.07 x 10(-5)), reaffirming variant-level analysis. In summary, this large study identified several rare and low-frequency variants and genes that may contribute to EOC susceptibility, albeit with possible small effects. Future studies that integrate epidemiology, sequencing, and functional assays are needed to further unravel the unexplained heritability and biology of this disease
C1 [Permuth, Jennifer B.; Reid, Brett M.; Monteiro, Alvaro; Mendoza-Fandino, Gustavo; Phelan, Catherine M.; Sellers, Thomas A.] H Lee Moffitt Canc Ctr & Res Inst, Dept Canc Epidemiol, Tampa, FL USA.
[Pirie, Ailith; Dennis, Joe; Pharoah, Paul D. P.] Univ Cambridge, Strangeways Res Lab, Dept Publ Hlth & Primary Care, Cambridge, England.
[Chen, Y. Ann; Lin, Hui-Yi; Chen, Zhihua] H Lee Moffitt Canc Ctr & Res Inst, Dept Biostat & Bioinformat, Tampa, FL USA.
[Chenevix-Trench, Georgia; AOCS Study Grp; Australian Canc Study Ovarian Canc] QIMR Berghofer Med Res Inst, Genet & Computat Biol Dept, Brisbane, Qld, Australia.
[Anton-Culver, Hoda] Univ Calif Irvine, UCI Sch Med, Dept Epidemiol, Genet Epidemiol Res Inst, Irvine, CA USA.
[Bandera, Elisa V.] Rutgers Canc Inst New Jersey, Canc Prevent & Control Program, New Brunswick, NJ USA.
[Bisogna, Maria; Levine, Douglas A.] Mem Sloan Kettering Canc Ctr, Dept Surg, Gynecol Serv, New York, NY 10021 USA.
[Brinton, Louise] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[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.
[Carney, Michael E.] Univ Hawaii, John A Burns Sch Med, Dept Obstet & Gynecol, Honolulu, HI 96822 USA.
[Cook, Linda S.] Univ New Mexico, Dept Internal Med, Div Epidemiol & Biostat, Albuquerque, NM 87131 USA.
[Cramer, Daniel W.; Terry, Kathryn L.] Brigham & Womens Hosp, Obstet & Gynecol Epidemiol Ctr, 75 Francis St, Boston, MA 02115 USA.
[Cunningham, Julie M.] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA.
[Cybulski, Cezary; Gronwald, Jacek; Jakubowska, Anna; Lubinski, Jan] Pomeranian Med Univ, Dept Genet & Pathol, Int Hereditary Canc Ctr, Szczecin, Poland.
[D'Aloisio, Aimee A.] Social & Sci Syst Inc, Durham, NC USA.
[Doherty, Jennifer Anne] Dartmouth Coll, Geisel Sch Med, Dept Epidemiol, Hanover, NY USA.
[Earp, Madalene; Goode, Ellen L.] Mayo Clin, Div Epidemiol, Dept Hlth Sci Res, Rochester, MN USA.
[Edwards, Robert P.; Modugno, Rosemary] Univ Pittsburgh, Sch Med, Dept Obstet Gynecol & Reprod Sci, Div Gynecol Oncol, Pittsburgh, PA USA.
[Edwards, Robert P.; Modugno, Rosemary] Magee Womens Res Inst, Womens Canc Res Program, Ovarian Canc Ctr Excellence, Pittsburgh, PA USA.
[Edwards, Robert P.; Modugno, Rosemary] Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA.
[Fridley, Brooke L.] Univ Kansas, Med Ctr, Dept Biostat, Kansas City, KS 66103 USA.
[Gayther, Simon A.; Pearce, Celeste L.; Ramus, Susan J.; Wu, Anna H.] Univ Southern Calif, Norris Comprehens Canc Ctr, Keck Sch Med, Dept Prevent Med, Los Angeles, CA USA.
[Gentry-Maharaj, Aleksandra; Menon, Usha] UCL, Womens Canc Inst Womens Hlth, London, England.
[Goodman, Marc T.] Cedars Sinai Med Ctr, Samuel Oshin Comprehens Canc Inst, Canc Prevent & Control, 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.
[Hogdall, Estrid; Jensen, Allan; Kjaer, Suzanne K.] Danish Canc Soc, Res Ctr, Dept Virus Lifestyle & Genes, Copenhagen, Denmark.
[Hogdall, Estrid] Univ Copenhagen, Herlev Hosp, Dept Pathol, Mol Unit, Copenhagen, Denmark.
[Iversen, Edwin S.] Duke Univ, Dept Stat Sci, Durham, NC USA.
[Karlan, Beth Y.; Thompson, Pamela J.] Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Inst, Womens Canc Program, Los Angeles, CA 90048 USA.
[Kelemen, Linda E.] Med Univ South Carolina, Coll Med, Dept Publ Hlth Sci, Charleston, SC USA.
[Kjaer, Suzanne K.] Univ Copenhagen, Rigshosp, Dept Gynaecol, Copenhagen, Denmark.
[Kraft, Peter] Harvard TH Chan Sch Publ Hlth, Program Genet Epidemiol & Stat Genet, Boston, MA USA.
[Le, Nhu D.] BC Canc Agcy, Canc Control Res, Vancouver, BC, Canada.
[Lissowska, Jolanta] Maria Sklodowska Curie Mem Canc Ctr, Dept Canc Epidemiol & Prevent, Warsaw, Poland.
[Matsuo, Keitaro] Aichi Canc Ctr, Res Inst, Div Mol Med, Nagoya, Aichi, Japan.
[Modugno, Rosemary] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15260 USA.
[Moysich, Kirsten B.] Roswell Pk Canc Inst, Dept Canc Prevent & Control, Buffalo, NY 14263 USA.
[Nakanishi, Toru] Aichi Canc Ctr, Cent Hosp, Dept Gynecol Oncol, Nagoya, Aichi, Japan.
[Ness, Roberta B.] Univ Texas Sch Publ Hlth, Houston, TX USA.
[Olson, Sara; Orlow, Irene] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA.
[Pearce, Celeste L.] Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA.
[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.
[Poole, Elizabeth M.; Tworoger, Shelley S.] Brigham & Womens Hosp, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA.
[Poole, Elizabeth M.; Tworoger, Shelley S.] Harvard Med Sch, Boston, MA USA.
[Poole, Elizabeth M.; Tworoger, Shelley S.] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.
[Rossing, Mary Anne] 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.
[Sandler, Dale P.; Taylor, Jack A.] NIEHS, Epidemiol Branch, Div Intramural Res, NIH, Res Triangle Pk, NC 27709 USA.
[Shu, Xiao-Ou] Vanderbilt Univ, Sch Med, Nashville, TN 37212 USA.
[Song, Honglin; Pharoah, Paul D. P.] Univ Cambridge, Strangeways Res Lab, Dept Oncol, Cambridge, England.
[Teo, Soo-Hwang] Canc Res Malaysia, Subang Jaya, Malaysia.
[Teo, Soo-Hwang] Univ Malaya, Med Ctr, Kuala Lumpur, Malaysia.
[Webb, Penelope M.] QIMR Berghofer Med Res Inst, Populat Hlth Dept, Herston, Qld, Australia.
[Wentzensen, Nicolas; Yang, Hannah] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Wilkens, Lynne R.] Univ Hawaii, Ctr Canc, Canc Epidemiol Program, Honolulu, HI 96822 USA.
[Winham, Stacey] Mayo Clin, Div Biomed Stat & Informat, Dept Hlth Sci Res, Rochester, MN USA.
[Woo, Yin-Ling] Univ Malaya, Med Ctr, Dept Obstet & Gynaecol, Kuala Lumpur, Malaysia.
[Zheng, Wei] Vanderbilt Univ, Sch Med, Vanderbilt Epidemiol Ctr, Nashville, TN 37212 USA.
[Zheng, Wei] Vanderbilt Univ, Sch Med, Vanderbilt Ingram Canc Ctr, Nashville, TN 37212 USA.
[Ziogas, Argyrios] Univ Calif Irvine, Dept Epidemiol, Irvine, CA USA.
[Schildkraut, Joellen M.] Duke Univ, Med Ctr, Dept Community & Family Med, Durham, NC 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.
RP Sellers, TA (reprint author), H Lee Moffitt Canc Ctr & Res Inst, 12902 Magnolia Dr, Tampa, FL 33612 USA.
RI Gronwald, Jacek/A-4576-2017; Brooks-Wilson, Angela/E-9399-2012;
OI Gronwald, Jacek/0000-0002-3643-2871; Brooks-Wilson,
Angela/0000-0003-1009-6408; taylor, jack/0000-0001-5303-6398; Sandler,
Dale/0000-0002-6776-0018; Matsuo, Keitaro/0000-0003-1761-6314; Winham,
Stacey/0000-0002-8492-9102
FU National Institute of Health; Genetic Associations and Mechanisms in
Oncology (GAME-ON), a NCI Cancer Post-GWAS Initiative [U19-CA148112];
NHMRC; Medical Research Council studentship; U.S. National Institutes of
Health [R01-CA112523, R01-CA87538, R01- CA58598, N01-CN-55424,
N01-PC-67001]; DOD [DAMD17-02-1-0669]; NCI [K07-CA080668, R01-CA95023,
P50-CA159981]; NIH/National Center for Research Resources/General
Clinical Research Center grant [M01-RR000056, R01-CA126841]; Ministry of
Health, Labour and Welfare; American Cancer Society Early Detection
Professorship [SIOP-06-258-01-COUN]; L & S Milken Foundation; National
Cancer Institute, Bethesda, MD [R01- CA61107]; Danish Cancer Society,
Copenhagen, Denmark [94 222 52]; Mermaid I project; National Institutes
of Health [R01-CA122443, P30-CA15083, P50-CA136393, R01-CA76016,
R01-CA54419, P50-CA105009, P01-CA87696, R01-CA49449]; Mayo Foundation;
Minnesota Ovarian Cancer Alliance; Fred C. and Katherine B. Andersen
Foundation; Malaysian Ministry of Higher Education [UM.C/HIR/MOHE/06];
Cancer Research Initiatives Foundation; Department of Defense
[DAMD17-02-1-0666, W81XWH- 10-1-02802]; OHSU Foundation; Pomeranian
Medical University; National Cancer Institute [NIH-K07 CA095666,
R01-CA83918, NIH-K22-CA138563, P30-CA072720]; Cancer Institute of New
Jersey; NCI CCSG award [P30- CA008748]; Intramural Research Program of
the NCI; Cancer Research UK [C490/A10119 C490/A10124]; UK National
Institute for Health Research Biomedical Research Centres at the
University of Cambridge, SEARCH team; National Institute of
Environmental Health Sciences [Z01ES044005]; National Institute for
Health [R37-CA070867]; Eve Appeal (The Oak Foundation); National
Institute for Health Research University College London Hospitals
Biomedical Research Centre; Lon V Smith Foundation [LVS-39420];
California Cancer Research Program [00-01389V-20170, 2II0200];
Biostatistics and Cancer Informatics Core Facilities at the H. Lee
Moffitt Cancer Center & Research Institute, an NCI designated
Comprehensive Cancer Center [P30-CA076292]; [MOP-86727]; [MSH-87734]
FX Funding for this study was supported by the National Institute of Health
and the Genetic Associations and Mechanisms in Oncology (GAME-ON), a NCI
Cancer Post-GWAS Initiative (U19-CA148112). In addition, we acknowledge
the following: AUS: 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). The Australian Ovarian Cancer Study Management Group (D.
Bowtell, G. Chenevix-Trench, A. deFazio, D. Gertig, A. Green, P. Webb)
and ACS Investigators (A. Green, P. Parsons, N. Hayward, P. Webb, D.
Whiteman) thank all the clinical and scientific collaborators (see
http://www.aocstudy.org/) and the women for their contribution. GCT & PW
are supported by Fellowships from NHMRC; AP is funded by a Medical
Research Council studentship; DOV: U.S. National Institutes of Health
R01-CA112523 and R01-CA87538; HAW: U.S. National Institutes of Health
(R01- CA58598, N01-CN-55424 and N01-PC-67001); HOP: DOD DAMD17-02-1-0669
and NCI K07-CA080668, R01-CA95023, P50-CA159981; NIH/National Center for
Research Resources/General Clinical Research Center grant M01-RR000056;
R01-CA126841; JPN: Grant-in-Aid for the Third Term Comprehensive 10-Year
Strategy for Cancer Control from the Ministry of Health, Labour and
Welfare; LAX: American Cancer Society Early Detection Professorship
(SIOP-06-258-01-COUN) and the L & S Milken Foundation; MAL: Funding for
this study was provided 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.; MAC and
MAY: National Institutes of Health (R01-CA122443, P30-CA15083,
P50-CA136393), Mayo Foundation; Minnesota Ovarian Cancer Alliance; Fred
C. and Katherine B. Andersen Foundation; MAS: Malaysian Ministry of
Higher Education (UM.C/HIR/MOHE/06) and Cancer Research Initiatives
Foundation; NCO: National Institutes of Health (R01-CA76016) and the
Department of Defense (DAMD17-02-1-0666); NEC: National Institutes of
Health R01-CA54419 and P50-CA105009 and Department of Defense W81XWH-
10-1-02802; NHS: National Institute of Health (P01-CA87696 and
R01-CA49449); ORE: OHSU Foundation; POC: Pomeranian Medical University;
NJO: National Cancer Institute (NIH-K07 CA095666, R01-CA83918,
NIH-K22-CA138563, and P30-CA072720), the Cancer Institute of New Jersey,
and NCI CCSG award (P30- CA008748). POL: Intramural Research Program of
the NCI; RMH: Cancer Research UK (no grant number is available); OVA:
(MOP-86727, MSH-87734; SEA: Cancer Research UK (C490/A10119
C490/A10124); UK National Institute for Health Research Biomedical
Research Centres at the University of Cambridge, SEARCH team, Craig
Luccarini, Caroline Baynes, Don Conroy; SIS: National Institute of
Environmental Health Sciences, (Z01ES044005); SWH: National Institute
for Health (R37-CA070867); UKO: The UKOPS study was funded by The Eve
Appeal (The Oak Foundation) and supported by the National Institute for
Health Research University College London Hospitals Biomedical Research
Centre. We particularly thank I. Jacobs, M. Widschwendter, E. Wozniak,
A. Ryan, J. Ford and N.; Balogun for their contribution to the study;
UCI: NIH R01-CA058860, NIH R01-CA092044, US Public Health Service
PSA-042205, and the Lon V Smith Foundation grant LVS-39420; USC:
P01-CA17054, P30-CA14089, R01-CA61132, N01-PC67010, R03-CA113148,
R03-CA115195, N01-CN025403, and California Cancer Research Program
(00-01389V-20170, 2II0200). This study was also supported in part by the
Biostatistics and Cancer Informatics Core Facilities at the H. Lee
Moffitt Cancer Center & Research Institute, an NCI designated
Comprehensive Cancer Center (P30-CA076292).
NR 56
TC 0
Z9 0
U1 2
U2 2
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 AUG 15
PY 2016
VL 25
IS 16
BP 3600
EP 3612
DI 10.1093/hmg/ddw196
PG 13
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA EJ4IO
UT WOS:000393180400018
PM 27378695
ER
PT J
AU Mohile, SG
Hurria, A
Cohen, HJ
Rowland, JH
Leach, CR
Arora, NK
Canin, B
Muss, HB
Magnuson, A
Flannery, M
Lowenstein, L
Allore, HG
Mustian, KM
Demark-Wahnefried, W
Extermann, M
Ferrell, B
Inouye, SK
Studenski, SA
Dale, W
AF Mohile, Supriya G.
Hurria, Arti
Cohen, Harvey J.
Rowland, Julia H.
Leach, Corinne R.
Arora, Neeraj K.
Canin, Beverly
Muss, Hyman B.
Magnuson, Allison
Flannery, Marie
Lowenstein, Lisa
Allore, Heather G.
Mustian, Karen M.
Demark-Wahnefried, Wendy
Extermann, Martine
Ferrell, Betty
Inouye, Sharon K.
Studenski, Stephanie A.
Dale, William
TI Improving the Quality of Survivorship for Older Adults With Cancer
SO CANCER
LA English
DT Review
DE aging; elderly; quality of life; research priorities; survivorship
ID COMPREHENSIVE GERIATRIC ASSESSMENT; ELDERLY-PATIENTS; AGING RESEARCH;
CHEMOTHERAPY TOXICITY; INTERNATIONAL SOCIETY; ONCOLOGY RESEARCH;
CONTROLLED-TRIAL; CLINICAL-TRIALS; CARE; MULTICENTER
AB In May 2015, the Cancer and Aging Research Group, in collaboration with the National Cancer Institute and the National Institute on Aging through a U13 grant, convened a conference to identify research priorities to help design and implement intervention studies to improve the quality of life and survivorship of older, frailer adults with cancer. Conference attendees included researchers with multidisciplinary expertise and advocates. It was concluded that future intervention trials for older adults with cancer should: 1) rigorously test interventions to prevent the decline of or improve health status, especially interventions focused on optimizing physical performance, nutritional status, and cognition while undergoing cancer treatment; 2) use standardized care plans based on geriatric assessment findings to guide targeted interventions; and 3) incorporate the principles of geriatrics into survivorship care plans. Also highlighted was the need to integrate the expertise of interdisciplinary team members into geriatric oncology research, improve funding mechanisms to support geriatric oncology research, and disseminate high-impact results to the research and clinical community. In conjunction with the 2 prior U13 meetings, this conference provided the framework for future research to improve the evidence base for the clinical care of older adults with cancer. (C) 2016 American Cancer Society.
C1 [Mohile, Supriya G.] Univ Rochester, Dept Med, Rochester, NY 14642 USA.
[Hurria, Arti] City Hope Natl Med Ctr, Med Oncol & Expt Therapeut, 1500 E Duarte Rd, Duarte, CA 91010 USA.
[Cohen, Harvey J.] Duke Univ, Ctr Study Aging & Human Dev, Durham, NC USA.
[Rowland, Julia H.; Leach, Corinne R.] NCI, Off Canc Survivorship, Bethesda, MD 20892 USA.
[Arora, Neeraj K.] Patient Ctr Outcomes Res Inst, Washington, DC USA.
[Canin, Beverly] SCOREboard Advocacy Grp, Rochester, NY USA.
[Muss, Hyman B.] Univ N Carolina, Breast Canc, Geriatr Oncol Program, Sch Med, Chapel Hill, NC USA.
[Magnuson, Allison] Univ Rochester, Div Med Oncol, 601 Elmwood Ave, Rochester, NY 14642 USA.
[Flannery, Marie; Mustian, Karen M.] Univ Rochester, Dept Surg, 601 Elmwood Ave, Rochester, NY 14642 USA.
[Lowenstein, Lisa] Univ Texas MD Anderson Canc Ctr, Dept Hlth Serv Res, Houston, TX 77030 USA.
[Allore, Heather G.] Yale Univ, Dept Med & Publ Hlth Serv, New Haven, CT USA.
[Demark-Wahnefried, Wendy] Univ Alabama Birmingham, Dept Nutr Sci, Birmingham, AL 35294 USA.
[Extermann, Martine] H Lee Moffitt Canc Ctr & Res Inst, Senior Adult Oncol Program, Tampa, FL USA.
[Ferrell, Betty] City Hope Natl Med Ctr, Dept Nursing, 1500 E Duarte Rd, Duarte, CA 91010 USA.
[Inouye, Sharon K.] Harvard Med Sch, Beth Israel Deaconess Med Ctr, Hebrew SeniorLife, Inst Aging Res, Boston, MA USA.
[Studenski, Stephanie A.] NIA, Bethesda, MD 20892 USA.
[Dale, William] Univ Chicago, Dept Med, Div Geriatr, 5841 S Maryland Ave, Chicago, IL 60637 USA.
RP Mohile, SG (reprint author), Univ Rochester, Med Ctr, Dept Med, 601 Elmwood Ave,Box 704, Rochester, NY 14642 USA.
EM Supriya_mohile@urmc.rochester.edu
OI Allore, Heather/0000-0001-7685-8175
FU National Institute on Aging [U13 AG038151]; American Cancer Society;
Patient-Centered Outcomes Research Institute [4634]; James Wilmot Cancer
Institute; Alliance for Clinical Trials in Oncology (National Cancer
Institute of the National Institutes of Health) [U10CA18082,
1UG1CA189823]; National Cancer Institute [UG1 CA189961]
FX Funded by grant U13 AG038151 from the National Institute on Aging. The
current study also was funded by the American Cancer Society and a
Patient-Centered Outcomes Research Institute Program contract (4634).
The work received support from the James Wilmot Cancer Institute, the
Alliance for Clinical Trials in Oncology (National Cancer Institute of
the National Institutes of Health under awards U10CA18082 and
1UG1CA189823), and grant UG1 CA189961 from the National Cancer
Institute. This work was made possible by the generous donors to the
James Wilmot Cancer Institute geriatric oncology philanthropy fund. All
statements in this report, including its findings and conclusions, are
solely those of the authors; do not necessarily represent the official
views of the funding agencies; and do not necessarily represent the
views of the Patient-Centered Outcomes Research Institute, its Board of
Governors, or Methodology Committee.
NR 47
TC 1
Z9 1
U1 2
U2 2
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 AUG 15
PY 2016
VL 122
IS 16
BP 2459
EP 2468
DI 10.1002/cncr.30053
PG 10
WC Oncology
SC Oncology
GA DW4MG
UT WOS:000383616600005
PM 27172129
ER
PT J
AU Siskind, RL
Andrasik, M
Karuna, ST
Broder, GB
Collins, C
Liu, A
Lucas, JP
Harper, GW
Renzullo, PO
AF Siskind, Rona L.
Andrasik, Michele
Karuna, Shelly T.
Broder, Gail B.
Collins, Clare
Liu, Albert
Lucas, Jonathan Paul
Harper, Gary W.
Renzullo, Philip O.
TI Engaging Transgender People in NIH-Funded HIV/AIDS Clinical Trials
Research
SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
LA English
DT Article
DE transgender; HIV; AIDS; clinical trials; research; NIH
ID PARTICIPANTS; HVTN
AB In 2009, the National Institutes of Health recognized the need to expand knowledge of lesbian, gay, bisexual, and transgender (LGBT) health and commissioned the Institute of Medicine to report on the health of these populations in the United States. The resulting Institute of Medicine publication called for more knowledge of the health of LGBT populations, as well as improved methodologies to reach them, more LGBT-focused research, and enhanced training programs and cultural competency of physicians and researchers. Several of the National Institutes of Health-funded HIV/AIDS clinical trials networks, including the Adolescent Medicine Trials Network for HIV/AIDS Interventions, HIV Prevention Trials Network, HIV Vaccine Trials Network, and Microbicide Trials Network, have focused attention on engaging transgender (TG) individuals in research. They have identified issues that transcend the nature of research (ie, treatment or prevention, adult or adolescent) and have adopted various approaches to effectively engage the TG community. Each network has recognized the importance of developing partner-ships to build trust with and seek input from TG individuals on research plans and policies. They have established standing advisory groups and convened consultations for this purpose. To ensure that trial data are reflective of the participants they are seeking to enroll, they have reviewed and revised data collection forms to incorporate the 2-step method of collecting sex at birth and gender identity as 2 independent variables, and some have also revised research protocol templates and policies for concept development to ensure that they are appropriate for the inclusion of TG participants. The networks have also initiated trainings to enhance cultural sensitivity and developed a range of materials and resources for network and clinical research site staff. They continue to identify TG-specific research needs in an effort to be more responsive to and improve the health of TG individuals, particularly related to HIV/AIDS.
C1 [Siskind, Rona L.; Renzullo, Philip O.] NIAID, Div Aids, NIH, 5601 Fishers Lane,Room 8D28A, Bethesda, MD 20852 USA.
[Andrasik, Michele; Karuna, Shelly T.; Broder, Gail B.] Fred Hutchinson Canc Res Ctr, HIV Vaccine Trials Network, 1124 Columbia St, Seattle, WA 98104 USA.
[Collins, Clare] Microbicide Trials Network, Pittsburgh, PA USA.
[Liu, Albert] San Francisco Dept Publ Hlth, Bridge HIV, San Francisco, CA USA.
[Lucas, Jonathan Paul] FHI360, HIV Prevent Trials Network, Durham, NC USA.
[Harper, Gary W.] Univ Michigan, Sch Publ Hlth, Ann Arbor, MI 48109 USA.
RP Siskind, RL (reprint author), NIAID, Div Aids, NIH, 5601 Fishers Lane,Room 8D28A, Bethesda, MD 20852 USA.
EM rsiskind@niaid.nih.gov
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development (NICHD); National Institute on Drug Abuse (NIDA); National
Institute of Mental Health (NIMH) [U01HD040533, U01HD040474]; National
Institute of Allergy and Infectious Diseases (NIAID); NIMH; NIDA
[UM1AI068619, UM1AI068617, UM1AI068613]; NIAID [UM1AI68614, UM1AI68618,
UM1AI68635]; NICHD; NIMH [UM1AI068633, UM1AI068615, UM1AI106707]
FX Overall support for the Adolescent Medicine Trials Network for HIV/AIDS
Interventions is funded by Eunice Kennedy Shriver National Institute of
Child Health and Human Development (NICHD) with supplemental funding
from the National Institute on Drug Abuse (NIDA) and the National
Institute of Mental Health (NIMH) (U01HD040533 and U01HD040474); support
for the HIV Prevention Trials Network is provided by the National
Institute of Allergy and Infectious Diseases (NIAID), NIMH, and NIDA
(UM1AI068619, UM1AI068617, and UM1AI068613); support for the HIV Vaccine
Trials Network is provided by NIAID (UM1AI68614, UM1AI68618, and
UM1AI68635); support for the Microbicides Trials Network (MTN) is
provided by NIAID with co-funding from NICHD and the NIMH (UM1AI068633,
UM1AI068615, and UM1AI106707). The content is solely the responsibility
of the authors and does not necessarily represent the official views of
the NIAID, NICHD, NIDA, NIMH, or the National Institutes of Health.
NR 14
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 1525-4135
EI 1077-9450
J9 JAIDS-J ACQ IMM DEF
JI JAIDS
PD AUG 15
PY 2016
VL 72
SU 3
BP S243
EP S247
PG 5
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA DY6YM
UT WOS:000385275700007
PM 27429190
ER
PT J
AU Naradikian, MS
Myles, A
Beiting, DP
Roberts, KJ
Dawson, L
Herati, RS
Bengsch, B
Linderman, SL
Stelekati, E
Spolski, R
Wherry, EJ
Hunter, C
Hensley, SE
Leonard, WJ
Cancro, MP
AF Naradikian, Martin S.
Myles, Arpita
Beiting, Daniel P.
Roberts, Kenneth J.
Dawson, Lucas
Herati, Ramin Sedaghat
Bengsch, Bertram
Linderman, Susanne L.
Stelekati, Erietta
Spolski, Rosanne
Wherry, E. John
Hunter, Christopher
Hensley, Scott E.
Leonard, Warren J.
Cancro, Michael P.
TI Cutting Edge: IL-4, IL-21, and IFN-gamma Interact To Govern T-bet and
CD11c Expression in TLR-Activated B Cells
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID FOLLICULAR HELPER-CELLS; AUTOANTIBODY PRODUCTION; TRANSCRIPTION FACTOR;
AGED MICE; MEMORY; EXPANSION; RESPONSES; RECEPTOR; INFECTION; ANTIGEN
AB T-bet and CD11c expression in B cells is linked with IgG(2c) isotype switching, virus-specific immune responses, and humoral autoimmunity. However, the activation requisites and regulatory cues governing T-bet and CD11c expression in B cells remain poorly defined. In this article, we reveal a relationship among TLR engagement, IL-4, IL-21, and IFN-gamma that regulates T-bet expression in B cells. We find that IL-21 or IFN-gamma directly promote T-bet expression in the context of TLR engagement. Further, IL-4 antagonizes T-bet induction. Finally, IL-21, but not IFN-gamma, promotes CD11c expression independent of T-bet. Using influenza virus and Heligmosomoides polygyrus infections, we show that these interactions function in vivo to determine whether T-bet(+) and CD11c(+) B cells are formed. These findings suggest that T-bet(+) B cells seen in health and disease share the common initiating features of TLR-driven activation within this circumscribed cytokine milieu.
C1 [Naradikian, Martin S.; Myles, Arpita; Roberts, Kenneth J.; Cancro, Michael P.] Univ Penn, Perelman Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA.
[Naradikian, Martin S.; Myles, Arpita; Beiting, Daniel P.; Dawson, Lucas; Herati, Ramin Sedaghat; Bengsch, Bertram; Linderman, Susanne L.; Stelekati, Erietta; Wherry, E. John; Hunter, Christopher; Hensley, Scott E.; Cancro, Michael P.] Univ Penn, Perelman Sch Med, Inst Immunol, Philadelphia, PA 19104 USA.
[Beiting, Daniel P.; Dawson, Lucas; Hunter, Christopher] Univ Penn, Sch Vet Med, Philadelphia, PA 19104 USA.
[Herati, Ramin Sedaghat] Univ Penn, Perelman Sch Med, Dept Med, Philadelphia, PA 19104 USA.
[Bengsch, Bertram; Linderman, Susanne L.; Stelekati, Erietta; Wherry, E. John; Hensley, Scott E.] Univ Penn, Perelman Sch Med, Dept Microbiol, Philadelphia, PA 19104 USA.
[Linderman, Susanne L.; Hensley, Scott E.] Wistar Inst Anat & Biol, 3601 Spruce St, Philadelphia, PA 19104 USA.
[Spolski, Rosanne; Leonard, Warren J.] NHLBI, Lab Mol Immunol, NIH, Bldg 10, Bethesda, MD 20892 USA.
[Spolski, Rosanne; Leonard, Warren J.] NHLBI, Ctr Immunol, NIH, Bldg 10, Bethesda, MD 20892 USA.
RP Cancro, MP (reprint author), Univ Penn, Perelman Sch Med, 284 John Morgan Bldg,3620 Hamilton Walk, Philadelphia, PA 19104 USA.
EM cancro@mail.med.upenn.edu
FU NCI NIH HHS [T32 CA009171]; NIA NIH HHS [R01 AG030227]; NIAID NIH HHS
[R01 AI118691, K08 AI114852, R01 AI108686, R01 AI113047, T32 AI055428]
NR 31
TC 2
Z9 2
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 AUG 15
PY 2016
VL 197
IS 4
BP 1023
EP 1028
DI 10.4049/jimmunol.1600522
PG 6
WC Immunology
SC Immunology
GA DY3NB
UT WOS:000384999100003
PM 27430719
ER
PT J
AU Su, P
Chen, S
Zheng, YH
Zhou, HY
Yan, CH
Yu, F
Zhang, YG
He, L
Zhang, Y
Wang, YM
Wu, L
Wu, XA
Yu, BK
Ma, LY
Yang, ZR
Wang, JH
Zhao, GX
Zhu, JF
Wu, ZY
Sun, B
AF Su, Pan
Chen, Sheng
Zheng, Yu Han
Zhou, Hai Yan
Yan, Cheng Hua
Yu, Fang
Zhang, Ya Guang
He, Lan
Zhang, Yuan
Wang, Yanming
Wu, Lei
Wu, Xiaoai
Yu, Bingke
Ma, Li Yan
Yang, Zhiru
Wang, Jianhua
Zhao, Guixian
Zhu, Jinfang
Wu, Zhi-Ying
Sun, Bing
TI Novel Function of Extracellular Matrix Protein 1 in Suppressing Th17
Cell Development in Experimental Autoimmune Encephalomyelitis
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID REGULATORY T-CELLS; GROWTH-FACTOR-BETA; TGF-BETA; MULTIPLE-SCLEROSIS;
DENDRITIC CELLS; HUMAN SKIN; DIFFERENTIATION; ACTIVATION; EXPRESSION;
RESPONSES
AB Multiple sclerosis (MS) is a chronic inflammatory disease of the CNS characterized by demyelination and axonal damage. Experimental autoimmune encephalomyelitis (EAE) is a well-established animal model for human MS. Although Th17 cells are important for disease induction, Th2 cells are inhibitory in this process. In this article, we report the effect of a Th2 cell product, extracellular matrix protein 1 (ECM1), on the differentiation of Th17 cells and the development of EAE. Our results demonstrated that ECM1 administration from day 1 to day 7 following the EAE induction could ameliorate the Th17 cell responses and EAE development in vivo. Further study of the mechanism revealed that ECM1 could interact with alpha v integrin on dendritic cells and block the alpha v integrin-mediated activation of latent TGF-beta, resulting in an inhibition of Th17 cell differentiation at an early stage of EAE induction. Furthermore, overexpression of ECM1 in vivo significantly inhibited the Th17 cell response and EAE induction in ECM1 transgenic mice. Overall, our work has identified a novel function of ECM1 in inhibiting Th17 cell differentiation in the EAE model, suggesting that ECM1 may have the potential to be used in clinical applications for understanding the pathogenesis of MS and its diagnosis.
C1 [Su, Pan; Zheng, Yu Han; Zhou, Hai Yan; Yan, Cheng Hua; Zhang, Ya Guang; He, Lan; Zhang, Yuan; Wang, Yanming; Ma, Li Yan; Sun, Bing] Chinese Acad Sci, State Key Lab Cell Biol, CAS Ctr Excellence Mol Cell Sci, Inst Biochem & Cell Biol,Shanghai Inst Biol Sci, Shanghai 200031, Peoples R China.
[Chen, Sheng; Wu, Lei; Wu, Zhi-Ying] Zhejiang Univ, Sch Med, Dept Neurol, Hangzhou 310058, Zhejiang, Peoples R China.
[Chen, Sheng; Wu, Lei; Wu, Zhi-Ying] Zhejiang Univ, Sch Med, Res Ctr Neurol, Affiliated Hosp 2, Hangzhou 310058, Zhejiang, Peoples R China.
[Chen, Sheng; Wu, Lei; Wu, Zhi-Ying] Zhejiang Univ, Sch Med, Collaborat Innovat Ctr Brain Sci, Hangzhou 310058, Zhejiang, Peoples R China.
[Chen, Sheng] Fujian Med Univ, Affiliated Hosp 1, Dept Neurol, Fuzhou 350004, Peoples R China.
[Chen, Sheng] Fujian Med Univ, Affiliated Hosp 1, Inst Neurol, Fuzhou 350004, Peoples R China.
[Yu, Fang] NIAID, Immunol Lab, NIH, Bldg 10, Bethesda, MD 20892 USA.
[Wu, Xiaoai; Yu, Bingke; Yang, Zhiru] Novo Nordisk Res Ctr, Beijing 100000, Peoples R China.
[Wang, Jianhua] Chinese Acad Sci, Inst Pasteur Shanghai, Key Lab Mol Virol & Immunol, Shanghai 200031, Peoples R China.
[Zhao, Guixian] Fudan Univ, Dept Neurol, Shanghai Med Coll, Huashan Hosp, Shanghai 200032, Peoples R China.
[Zhao, Guixian] Fudan Univ, Inst Neurol, Shanghai Med Coll, Huashan Hosp, Shanghai 200032, Peoples R China.
RP Sun, B (reprint author), Chinese Acad Sci, State Key Lab Cell Biol, CAS Ctr Excellence Mol Cell Sci, Inst Biochem & Cell Biol,Shanghai Inst Biol Sci, Shanghai 200031, Peoples R China.; Zhu, JF; Wu, ZY; Sun, B (reprint author), Chinese Acad Sci, Inst Biochem & Cell Biol, Shanghai Inst Biol Sci, 320 Yue Yang Rd, Shanghai 200031, Peoples R China.
EM jfZhu@niaid.nih.gov; zhiyingwu@zju.edu.cn; bsun@sibs.ac.cn
RI Zhu, Jinfang/B-7574-2012
FU Intramural NIH HHS [ZIA AI001169-04]
NR 50
TC 0
Z9 0
U1 3
U2 3
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 AUG 15
PY 2016
VL 197
IS 4
BP 1054
EP 1064
DI 10.4049/jimmunol.1502457
PG 11
WC Immunology
SC Immunology
GA DY3NB
UT WOS:000384999100007
PM 27316685
ER
PT J
AU Cao, X
Lu, Y
Zhang, XY
Kovalovsky, D
AF Cao, Xin
Lu, Ying
Zhang, Xianyu
Kovalovsky, Damian
TI Zbtb1 Safeguards Genome Integrity and Prevents p53-Mediated Apoptosis in
Proliferating Lymphoid Progenitors
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID CD8(+) T-CELLS; ZINC-FINGER; PLZF CONTROLS; CHK1; REPLICATION;
PHOSPHORYLATION; LINEAGE; REPAIR; BCL-2; ATR
AB Expression of the transcription factor Zbtb1 is required for normal lymphoid development. We report in the present study that Zbtb1 maintains genome integrity in immune progenitors, without which cells undergo increased DNA damage and p53-mediated apoptosis during replication and differentiation. Increased DNA damage in Zbtb1-mutant (ScanT) progenitors was due to increased sensitivity to replication stress, which was a consequence of inefficient activation of the S-phase checkpoint response. Increased p53-mediated apoptosis affected not only lymphoid but also myeloid development in competitive bone marrow chimeras, and prevention of apoptosis by transgenic Bcl2 expression and p53 deficiency rescued lymphoid as well as myeloid development from Zbtb1-mutant progenitors. Interestingly, however, protection from apoptosis rescued only the early stages of T cell development, and thymocytes remained arrested at the double-negative 3 developmental stage, indicating a strict requirement of Zbtb1 at later T cell developmental stages. Collectively, these results indicate that Zbtb1 prevents DNA damage in replicating immune progenitors, allowing the generation of B cells, T cells, and myeloid cells.
C1 [Cao, Xin] Northwest Univ Nationalities, Coll Life Sci & Engn, Lanzhou 730030, Peoples R China.
[Cao, Xin; Lu, Ying; Zhang, Xianyu; Kovalovsky, Damian] NCI, Expt Immunol Branch, NIH, 9000 Rockville Pike,Bldg 10-4B17, Bethesda, MD 20892 USA.
RP Kovalovsky, D (reprint author), NCI, Expt Immunol Branch, NIH, 9000 Rockville Pike,Bldg 10-4B17, Bethesda, MD 20892 USA.
EM kovalovskyd@mail.nih.gov
FU Intramural NIH HHS [ZIA BC011429-02, ZIA BC011429-01, Z99 CA999999, ZIA
BC011429-03, ZIA BC011429-04]; NCI NIH HHS [ZIA BC011429]
NR 36
TC 0
Z9 0
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 AUG 15
PY 2016
VL 197
IS 4
BP 1199
EP 1211
DI 10.4049/jimmunol.1600013
PG 13
WC Immunology
SC Immunology
GA DY3NB
UT WOS:000384999100020
PM 27402700
ER
PT J
AU Seedhom, MO
Hickman, HD
Wei, JJ
David, A
Yewdell, JW
AF Seedhom, Mina O.
Hickman, Heather D.
Wei, Jiajie
David, Alexandre
Yewdell, Jonathan W.
TI Protein Translation Activity: A New Measure of Host Immune Cell
Activation
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID CD8(+) T-CELLS; MEMORY PHENOTYPE; LYMPH-NODES; ANTIGEN; STIMULATION;
INNATE
AB We describe the in vivo ribopuromycylation (RPM) method, which uses a puromycin-specific Ab to fluorescently label ribosome-bound puromycylated nascent chains, enabling measurement of translational activity via immunohistochemistry or flow cytometry. Tissue staining provides a unique view of virus-induced activation of adaptive, innate, and stromal immune cells. RPM flow precisely quantitates virus-induced activation of lymphocytes and innate immune cells, and it provides a unique measure of immune cell deactivation and quiescence. Using RPM we find that high endothelial cells in draining lymph nodes rapidly increase translation in the first day of vaccinia virus infection. We also find a population of constitutively activated splenic T cells in naive mice and further that most bone marrow T cells activate 3 d after vaccinia virus infection. Bone marrow T cell activation is nonspecific, IL-12-dependent, and induces innate memory T cell phenotypic markers. Thus, RPM measures translational activity to uniquely identify cell populations that participate in the immune response to pathogens, other foreign substances, and autoantigens.
C1 [Seedhom, Mina O.; Hickman, Heather D.; Wei, Jiajie; David, Alexandre; Yewdell, Jonathan W.] NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA.
[David, Alexandre] Inst Genom Fonct, Montpellier, France.
RP Yewdell, JW (reprint author), NIAID, NIH, 33 North Dr,Room 2E13C-1,Bldg 33, Bethesda, MD 20892 USA.
EM jyewdell@niaid.nih.gov
FU Intramural NIH HHS [ZIA AI000814-16]
NR 22
TC 0
Z9 0
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 AUG 15
PY 2016
VL 197
IS 4
BP 1498
EP 1506
DI 10.4049/jimmunol.1600088
PG 9
WC Immunology
SC Immunology
GA DY3NB
UT WOS:000384999100048
PM 27385780
ER
PT J
AU Doritchamou, JYA
Herrera, R
Aebig, JA
Morrison, R
Nguyen, V
Reiter, K
Shimp, RL
MacDonald, NJ
Narum, DL
Fried, M
Duffy, PE
AF Doritchamou, Justin Yai Alamou
Herrera, Raul
Aebig, Joan A.
Morrison, Robert
Vu Nguyen
Reiter, Karine
Shimp, Richard L.
MacDonald, Nicholas J.
Narum, David L.
Fried, Michal
Duffy, Patrick E.
TI VAR2CSA Domain-Specific Analysis of Naturally Acquired Functional
Antibodies to Plasmodium falciparum Placental Malaria
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
DE malaria; pregnancy; multigravidae; VAR2CSA; DBL domains; functional
antibody; vaccine
ID CHONDROITIN-SULFATE-A; ADHESION-INHIBITORY ANTIBODIES; APICAL MEMBRANE
ANTIGEN-1; VARIANT SURFACE-ANTIGENS; INFECTED ERYTHROCYTES;
PREGNANT-WOMEN; BLOCKING ANTIBODIES; PARASITE ADHESION; VACCINE
CANDIDATE; MATERNAL MALARIA
AB Background. Placental malaria is caused by Plasmodium falciparum infected erythrocytes (IEs) that surface-express VAR2CSA and bind chondroitin sulfate A. The inflammatory response to placenta-sequestered parasites is associated with poor pregnancy outcomes, and protection may be mediated in part by VAR2CSA antibodies that block placental IE adhesion.
Methods. In this study, we used a new approach to assess VAR2CSA domains for functional epitopes recognized by naturally acquired antibodies. Antigen-specific immunoglobulin (Ig) G targeting Duffy binding like (DBL) domains from different alleles were sequentially purified from plasma pooled from multigravid women and then characterized using enzyme-linked immunosorbent assay, flow cytometry, and antiadhesion assays.
Results. Different DBL domain-specific IgGs could react to homologous as well as heterologous antigens and parasites, suggesting that conserved epitopes are shared between allelic variants. Homologous blocking of IE binding was observed with ID1-DBL2-ID2a-, DBL4-, and DBL5-specific IgG (range, 42%-75%), whereas partial cross-inhibition activity was observed with purified IgG specific to ID1-DBL2-ID2a and DBL4 antigens. Plasma retained broadly neutralizing activity after complete depletion of these VAR2CSA specificities.
Conclusions. Broadly neutralizing antibodies of multigravidae are not depleted on VAR2CSA recombinant antigens, and hence development of VAR2CSA vaccines based on a single construct and variant might induce antibodies with limited broadly neutralizing activity.
C1 [Doritchamou, Justin Yai Alamou; Herrera, Raul; Aebig, Joan A.; Morrison, Robert; Vu Nguyen; Reiter, Karine; Shimp, Richard L.; MacDonald, Nicholas J.; Narum, David L.; Fried, Michal; Duffy, Patrick E.] NIAID, Lab Malaria Immunol & Vaccinol, NIH, Twinbrook 1,Rm 1111,5640 Fishers Ln, Rockville, MD 20852 USA.
[Morrison, Robert] Seattle Biomed Res Inst, MOMS Project, 4 Nickerson St, Seattle, WA 98109 USA.
RP Duffy, PE (reprint author), NIAID, Lab Malaria Immunol & Vaccinol, NIH, Twinbrook 1,Rm 1111,5640 Fishers Ln, Rockville, MD 20852 USA.
EM patrick.duffy@nih.gov
FU Division of Intramural Research, National Institute of Allergy and
Infectious Diseases, National Institutes of Health
FX This work was supported by the Division of Intramural Research, National
Institute of Allergy and Infectious Diseases, National Institutes of
Health.
NR 49
TC 1
Z9 1
U1 1
U2 1
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 AUG 15
PY 2016
VL 214
IS 4
BP 577
EP 586
DI 10.1093/infdis/jiw197
PG 10
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA DY1JB
UT WOS:000384849600010
PM 27190180
ER
PT J
AU Powers, JH
Howard, K
Saretsky, T
Clifford, S
Hoffmann, S
Llorens, L
Talbot, G
AF Powers, John H., III
Howard, Kellee
Saretsky, Todd
Clifford, Sarah
Hoffmann, Steve
Llorens, Lily
Talbot, George
TI Patient-Reported Outcome Assessments as Endpoints in Studies in
Infectious Diseases
SO CLINICAL INFECTIOUS DISEASES
LA English
DT Article
DE infectious diseases; clinical trials; patient-reported outcomes;
endpoints; clinical practice
ID CONTROLLED SERIES; CYSTIC-FIBROSIS; CLINICAL-TRIALS; SYMPTOMS;
FOUNDATION; QUESTIONNAIRE; SULFANILAMIDE; RELIABILITY; ERYSIPELAS;
PNEUMONIA
AB The goal of administering medical interventions is to help patients live longer or live better. In keeping with this goal, there has been increasing interest in taking the "voice" of the patient into account during the development process, specifically in the evaluation of treatment benefits of medical interventions, and use of patient-centered outcome data to justify reimbursement. Patient-reported outcomes (PROs) are outcome assessments (OAs) used to define endpoints that can provide direct evidence of treatment benefit on how patients feel or function. When PROs are appropriately developed, they can increase the efficiency and clinical relevance of clinical trials. Several PROs have been developed for OA in specific infectious diseases indications, and more are under development. PROs also hold promise for use in evaluating adherence, adverse effects, satisfaction with care, and routine clinical practice.
C1 [Powers, John H., III] George Washington Univ, Sch Med, Washington, DC 20052 USA.
[Howard, Kellee; Saretsky, Todd; Clifford, Sarah] ICON PLC, San Francisco, CA USA.
[Hoffmann, Steve] Fdn Natl Inst Hlth, Bethesda, MD USA.
[Llorens, Lily] Llorens Consulting, Bay Village, OH USA.
[Talbot, George] Talbot Advisors LLC, Anna Maria, FL USA.
RP Powers, JH (reprint author), 15915 Emory Lane, Rockville, MD 20853 USA.
EM jpowers3@aol.com
FU Clinical Trials Transformation Initiative
FX This article appears as part of the supplement "Facilitating
Antibacterial Drug Development in a Time of Great Need," sponsored by
the Clinical Trials Transformation Initiative.
NR 44
TC 2
Z9 2
U1 3
U2 3
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 AUG 15
PY 2016
VL 63
SU 2
BP S52
EP S56
DI 10.1093/cid/ciw317
PG 5
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA DV8QX
UT WOS:000383202700007
PM 27481954
ER
PT J
AU Chen, HM
Larson, DR
AF Chen, Huimin
Larson, Daniel R.
TI What have single-molecule studies taught us about gene expression?
SO GENES & DEVELOPMENT
LA English
DT Review
DE fluorescence; single molecule; splicing; transcription
ID RNA-POLYMERASE-II; PRE-MESSENGER-RNA; TRANSCRIPTION FACTOR-BINDING;
START-SITE SELECTION; EMBRYONIC STEM-CELLS; U4/U6.U5 TRI-SNRNP;
REAL-TIME ANALYSIS; ESCHERICHIA-COLI; MAMMALIAN-CELLS; IN-VIVO
AB The production of a single mRNA is the result of many sequential steps, from docking of transcription factors to polymerase initiation, elongation, splicing, and, finally, termination. Much of our knowledge about the fundamentals of RNA synthesis and processing come from ensemble in vitro biochemical measurements. Single-molecule approaches are very much in this same reductionist tradition but offer exquisite sensitivity in space and time along with the ability to observe heterogeneous behavior and actually manipulate macromolecules. These techniques can also be applied in vivo, allowing one to address questions in living cells that were previously restricted to reconstituted systems. In this review, we examine the unique insights that single-molecule techniques have yielded on the mechanisms of gene expression.
C1 [Chen, Huimin; Larson, Daniel R.] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Larson, DR (reprint author), NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM dan.larson@nih.gov
RI Larson, Daniel/B-9829-2008
OI Larson, Daniel/0000-0001-9253-3055
FU Intramural Research Program of the National Cancer Institute
FX We acknowledge Maxime Dahan, Timothee Lionnet, Aaron Hoskins, Tineke
Lenstra, and Murali Palangat for critical comments on the manuscript. In
addition, both anonymous referees provided advice that greatly improved
the final review. This work was supported by the Intramural Research
Program of the National Cancer Institute.
NR 153
TC 1
Z9 1
U1 14
U2 14
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 AUG 15
PY 2016
VL 30
IS 16
BP 1796
EP 1810
DI 10.1101/gad.281725.116
PG 15
WC Cell Biology; Developmental Biology; Genetics & Heredity
SC Cell Biology; Developmental Biology; Genetics & Heredity
GA DW6CJ
UT WOS:000383733700003
PM 27601529
ER
PT J
AU Patterson, TF
Thompson, GR
Denning, DW
Fishman, JA
Hadley, S
Herbrecht, R
Kontoyiannis, DP
Marr, KA
Morrison, VA
Nguyen, MH
Segal, BH
Steinbach, WJ
Stevens, DA
Walsh, TJ
Wingard, JR
Young, JAH
Bennett, JE
AF Patterson, Thomas F.
Thompson, George R., III
Denning, David W.
Fishman, Jay A.
Hadley, Susan
Herbrecht, Raoul
Kontoyiannis, Dimitrios P.
Marr, Kieren A.
Morrison, Vicki A.
Nguyen, M. Hong
Segal, Brahm H.
Steinbach, William J.
Stevens, David A.
Walsh, Thomas J.
Wingard, John R.
Young, Jo-Anne H.
Bennett, John E.
TI Practice Guidelines for the Diagnosis and Management of Aspergillosis:
2016 Update by the Infectious Diseases Society of America
SO CLINICAL INFECTIOUS DISEASES
LA English
DT Article
DE aspergillosis; invasive aspergillosis; allergic aspergillosis; chronic
aspergillosis; fungal diagnostics; azoles; echniocandins; amphotericin
AB It is important to realize that guidelines cannot always account for individual variation among patients. They are not intended to supplant physician judgment with respect to particular patients or special clinical situations. IDSA considers adherence to these guidelines to be voluntary, with the ultimate determination regarding their application to be made by the physician in the light of each patient's individual circumstances.
C1 [Patterson, Thomas F.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA.
[Patterson, Thomas F.] South Texas Vet Hlth Care Syst, San Antonio, TX USA.
[Thompson, George R., III] Univ Calif Davis, Davis, CA 95616 USA.
[Denning, David W.] Univ Manchester, Univ South Manchester Hosp, Natl Aspergillosis Ctr, Manchester M13 9PL, Lancs, England.
[Fishman, Jay A.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Fishman, Jay A.] Harvard Med Sch, Boston, MA USA.
[Hadley, Susan] Tufts Med Ctr, Boston, MA USA.
[Herbrecht, Raoul] Univ Strasbourg, Strasbourg, France.
[Kontoyiannis, Dimitrios P.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Marr, Kieren A.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA.
[Marr, Kieren A.] Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA.
[Morrison, Vicki A.] Hennepin Cty Med Ctr, Minneapolis, MN 55415 USA.
[Morrison, Vicki A.; Young, Jo-Anne H.] Univ Minnesota, Minneapolis, MN USA.
[Nguyen, M. Hong] Univ Pittsburgh, Pittsburgh, PA 15260 USA.
[Segal, Brahm H.] SUNY Buffalo, Jacobs Sch Med & Biomed Sci, Buffalo, NY USA.
[Segal, Brahm H.] Roswell Pk Canc Inst, New York, NY USA.
[Steinbach, William J.] Duke Univ, Med Ctr, Durham, NC USA.
[Stevens, David A.] Calif Inst Med Res, San Jose, CA 95128 USA.
[Walsh, Thomas J.] New York Presbyterian Hosp, Weill Cornell Med Ctr, New York, NY USA.
[Wingard, John R.] Univ Florida, Gainesville, FL USA.
[Bennett, John E.] NIAID, Lab Clin Infect Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
RP Patterson, TF (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Div Infect Dis, San Antonio Ctr Med Mycol, 7703 Floyd Curl Dr,MSC 7881, San Antonio, TX 78229 USA.
EM patterson@uthscsa.edu
FU IDSA
FX Support for this guideline was provided by the IDSA.
NR 1
TC 9
Z9 9
U1 6
U2 6
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 AUG 15
PY 2016
VL 63
IS 4
BP 433
EP 442
DI 10.1093/cid/ciw444
PG 10
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA DV8QU
UT WOS:000383202400002
PM 27481947
ER
PT J
AU Xie, YDL
Chen, RY
Sereti, I
Zerbe, CS
Holland, SM
Browne, SK
AF Xie, Yingda L.
Chen, Ray Y.
Sereti, Irini
Zerbe, Christa S.
Holland, Steven M.
Browne, Sarah K.
TI Neutralizing Anti-Interferon-Gamma Autoantibody Levels May Not Correlate
With Clinical Course of Disease Reply
SO CLINICAL INFECTIOUS DISEASES
LA English
DT Letter
C1 [Xie, Yingda L.; Chen, Ray Y.; Zerbe, Christa S.; Holland, Steven M.] NIAID, Lab Clin Infect Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Sereti, Irini] NIAID, Immunoregulat Lab, NIH, Bldg 10, Bethesda, MD 20892 USA.
[Browne, Sarah K.] US FDA, Ctr Biol Evaluat & Res, Silver Spring, MD USA.
RP Holland, SM (reprint author), CRC B3-4141 MSC 1684, Bethesda, MD 20892 USA.
EM smh@nih.gov
NR 5
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 1058-4838
EI 1537-6591
J9 CLIN INFECT DIS
JI Clin. Infect. Dis.
PD AUG 15
PY 2016
VL 63
IS 4
BP 573
EP 574
DI 10.1093/cid/ciw352
PG 2
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA DV8QU
UT WOS:000383202400026
PM 27225244
ER
PT J
AU Patterson, TF
Thompson, GR
Denning, DW
Fishman, JA
Hadley, S
Herbrecht, R
Kontoyiannis, DP
Marr, KA
Morrison, VA
Nguyen, MH
Segal, BH
Steinbach, WJ
Stevens, DA
Walsh, TJ
Wingard, JR
Young, JAH
Bennett, JE
AF Patterson, Thomas F.
Thompson, George R., III
Denning, David W.
Fishman, Jay A.
Hadley, Susan
Herbrecht, Raoul
Kontoyiannis, Dimitrios P.
Marr, Kieren A.
Morrison, Vicki A.
Nguyen, M. Hong
Segal, Brahm H.
Steinbach, William J.
Stevens, David A.
Walsh, Thomas J.
Wingard, John R.
Young, Jo-Anne H.
Bennett, John E.
TI Practice Guidelines for the Diagnosis and Management of Aspergillosis:
2016 Update by the Infectious Diseases Society of America
SO CLINICAL INFECTIOUS DISEASES
LA English
DT Article
DE aspergillosis; invasive aspergillosis; allergic aspergillosis; chronic
aspergillosis; fungal diagnostics; azoles; echniocandins; amphotericin
ID INVASIVE FUNGAL-INFECTIONS; CELL TRANSPLANT RECIPIENTS; LIPOSOMAL
AMPHOTERICIN-B; CHRONIC PULMONARY ASPERGILLOSIS; ALLERGIC
BRONCHOPULMONARY ASPERGILLOSIS; CENTRAL-NERVOUS-SYSTEM; BRONCHOALVEOLAR
LAVAGE FLUID; CHRONIC GRANULOMATOUS-DISEASE; RANDOMIZED
CONTROLLED-TRIAL; SOLID-ORGAN TRANSPLANT
AB It is important to realize that guidelines cannot always account for individual variation among patients. They are not intended to supplant physician judgment with respect to particular patients or special clinical situations. IDSA considers adherence to these guidelines to be voluntary, with the ultimate determination regarding their application to be made by the physician in the light of each patient's individual circumstances.
C1 [Patterson, Thomas F.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA.
[Patterson, Thomas F.] South Texas Vet Hlth Care Syst, San Antonio, TX USA.
[Thompson, George R., III] Univ Calif Davis, Davis, CA 95616 USA.
[Denning, David W.] Univ Manchester, Univ South Manchester Hosp, Natl Aspergillosis Ctr, Manchester M13 9PL, Lancs, England.
[Fishman, Jay A.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Fishman, Jay A.] Harvard Med Sch, Boston, MA USA.
[Hadley, Susan] Tufts Med Ctr, Boston, MA USA.
[Herbrecht, Raoul] Univ Strasbourg, Strasbourg, France.
[Kontoyiannis, Dimitrios P.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Marr, Kieren A.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA.
[Marr, Kieren A.] Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA.
[Morrison, Vicki A.] Hennepin Cty Med Ctr, Minneapolis, MN 55415 USA.
[Morrison, Vicki A.; Young, Jo-Anne H.] Univ Minnesota, Minneapolis, MN USA.
[Nguyen, M. Hong] Univ Pittsburgh, Pittsburgh, PA 15260 USA.
[Segal, Brahm H.] SUNY Buffalo, Jacobs Sch Med & Biomed Sci, Buffalo, NY USA.
[Segal, Brahm H.] Roswell Pk Canc Inst, New York, NY USA.
[Steinbach, William J.] Duke Univ, Med Ctr, Durham, NC USA.
[Stevens, David A.] Calif Inst Med Res, San Jose, CA 95128 USA.
[Walsh, Thomas J.] New York Presbyterian Hosp, Weill Cornell Med Ctr, New York, NY USA.
[Wingard, John R.] Univ Florida, Gainesville, FL USA.
[Bennett, John E.] NIAID, Lab Clin Infect Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
RP Patterson, TF (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Div Infect Dis, San Antonio Ctr Med Mycol, 7703 Floyd Curl Dr,MSC 7881, San Antonio, TX 78229 USA.
EM patterson@uthscsa.edu
OI Herbrecht, Raoul/0000-0002-9381-4876
FU IDSA
FX Support for this guideline was provided by the IDSA.
NR 657
TC 27
Z9 27
U1 10
U2 11
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 AUG 15
PY 2016
VL 63
IS 4
BP E1
EP E60
DI 10.1093/cid/ciw326
PG 60
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA DV8QU
UT WOS:000383202400001
PM 27365388
ER
PT J
AU Eitan, E
Petralia, RS
Wang, YX
Indig, FE
Mattson, MP
Yao, PJ
AF Eitan, Erez
Petralia, Ronald S.
Wang, Ya-Xian
Indig, Fred E.
Mattson, Mark P.
Yao, Pamela J.
TI Probing extracellular Sonic hedgehog in neurons
SO BIOLOGY OPEN
LA English
DT Article
DE Sonic hedgehog; Hippocampal neurons; Extracellular vesicle; Filopodia
ID HIPPOCAMPAL-NEURONS; CAENORHABDITIS-ELEGANS; NMDA RECEPTORS; BRAIN;
PROLIFERATION; CYCLOPAMINE; INHIBITION; CEREBELLUM; ASTROCYTES;
EXPRESSION
AB The bioactivity of Sonic hedgehog (Shh) depends on specific lipid modifications; a palmitate at its N-terminus and a cholesterol at its C-terminus. This dual-lipid modification makes Shh molecules lipophilic, which prevents them from diffusing freely in extracellular space. Multiple lines of evidence indicate that Shh proteins are carried by various forms of extracellular vesicles (EVs). It also has been shown, for instance, that in some tissues Shh proteins are transported to neighboring cells directly via filopodia. We have previously reported that Shh proteins are expressed in hippocampal neurons. In this study we show that, in the hippocampus and cerebellum of postnatal day (P)2 rats, Shh is mostly found near or on the membrane surface of small neurites or filopodia. We also examined cultured hippocampal neurons where we observed noticeable and widespread Shh-immunolabeled vesicles located outside neurons. Through immunoelectron microscopy and biochemical analysis, we find Shh-containing EVs with a wide range of sizes. Unlike robust Shh activity in EVs isolated from cells overexpressing an N-terminal Shh fragment construct, we did not detect measurable Shh activity in EVs purified from the medium of cultured hippocampal neurons. These results suggest the complexity of the transcellular Shh signaling mechanisms in neurons.
C1 [Eitan, Erez; Mattson, Mark P.; Yao, Pamela J.] NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA.
[Petralia, Ronald S.; Wang, Ya-Xian] NIDCD, Adv Imaging Core, NIH, Bethesda, MD 20892 USA.
[Indig, Fred E.] NIA, Adv Imaging Core, Clin Invest Lab, Intramural Res Program, Baltimore, MD 21224 USA.
RP Yao, PJ (reprint author), NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA.
EM yaopa@grc.nia.nih.gov
FU Intramural Research Programs of National Institute on Aging - National
Institutes of Health; National Institute on Deafness and Other
Communication Disorders - National Institutes of Health
FX This study was supported by the Intramural Research Programs of National
Institute on Aging - National Institutes of Health and National
Institute on Deafness and Other Communication Disorders - National
Institutes of Health.
NR 50
TC 2
Z9 2
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 2046-6390
J9 BIOL OPEN
JI Biol. Open
PD AUG 15
PY 2016
VL 5
IS 8
BP 1086
EP 1092
DI 10.1242/bio.019422
PG 7
WC Biology
SC Life Sciences & Biomedicine - Other Topics
GA DU6DQ
UT WOS:000382304400009
PM 27387534
ER
PT J
AU Bellad, RM
Bang, A
Carlo, WA
McClure, EM
Meleth, S
Goco, N
Goudar, SS
Derman, RJ
Hibberd, PL
Patel, A
Esamai, F
Bucher, S
Gisore, P
Wright, LL
AF Bellad, Roopa M.
Bang, Akash
Carlo, Waldemar A.
McClure, Elizabeth M.
Meleth, Sreelatha
Goco, Norman
Goudar, Shivaprasad S.
Derman, Richard J.
Hibberd, Patricia L.
Patel, Archana
Esamai, Fabian
Bucher, Sherri
Gisore, Peter
Wright, Linda L.
CA HBB Study Grp
TI A pre-post study of a multi-country scale up of resuscitation training
of facility birth attendants: does Helping Babies Breathe training save
lives?
SO BMC PREGNANCY AND CHILDBIRTH
LA English
DT Article
ID MIDDLE-INCOME COUNTRIES; MORTALITY; ETHIOPIA; WOMEN
AB Background: Whether facility-based implementation of Helping Babies Breathe (HBB) reduces neonatal mortality at a population level in low and middle income countries (LMIC) has not been studied. Therefore, we evaluated HBB implementation in this context where our study team has ongoing prospective outcome data on all pregnancies regardless of place of delivery.
Methods: We compared outcomes of birth cohorts in three sites in India and Kenya pre-post implementation of a facility-based intervention, using a prospective, population-based registry in 52 geographic clusters. Our hypothesis was that HBB implementation would result in a 20 % decrease in the perinatal mortality rate (PMR) among births >= 1500 g.
Results: We enrolled 70,704 births during two 12-month study periods. Births within each site did not differ pre-post intervention, except for an increased proportion of <2500 g newborns and deliveries by caesarean section in the post period. There were no significant differences in PMR among all registry births; however, a post-hoc analysis stratified by birthweight documented improvement in <2500 g mortality in Belgaum in both registry and in HBB-trained facility births. No improvement in <2500 g mortality measures was noted in Nagpur or Kenya and there was no improvement in normal birth weight survival.
Conclusions: Rapid scale up of HBB training of facility birth attendants in three diverse sites in India and Kenya was not associated with consistent improvements in mortality among all neonates >= 1500 g; however, differential improvements in <2500 g survival in Belgaum suggest the need for careful implementation of HBB training with attention to the target population, data collection, and ongoing quality monitoring activities.
C1 [Bellad, Roopa M.; Goudar, Shivaprasad S.] KLE Univ Jawaharlal Nehru Med Coll, Belgaum, Karnataka, India.
[Bang, Akash] Mahatma Gandhi Inst Med Sci, Sevagram, Maharashtra, India.
[Carlo, Waldemar A.] Univ Alabama Birmingham, Birmingham, AL USA.
[McClure, Elizabeth M.; Meleth, Sreelatha; Goco, Norman] RTI Int, Durham, NC USA.
[Derman, Richard J.] Christiana Care Hlth Syst, Dept Obstet & Gynecol, Newark, DE USA.
[Hibberd, Patricia L.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Patel, Archana] Lata Med Res Fdn, Nagpur, Maharashtra, India.
[Patel, Archana] Indira Gandhi Govt Med Coll, Nagpur, Maharashtra, India.
[Esamai, Fabian; Gisore, Peter] Moi Univ Sch Med, Dept Child Hlth & Paediat, Eldoret, Kenya.
[Bucher, Sherri] Indiana Univ, Sch Med, Indianapolis, IN USA.
[Wright, Linda L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD 20892 USA.
[Wright, Linda L.] 5800 Nicholson Lane,1206, Rockville, MD 20852 USA.
RP Wright, LL (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD 20892 USA.; Wright, LL (reprint author), 5800 Nicholson Lane,1206, Rockville, MD 20852 USA.
EM lindawright.md@gmail.com
OI Somannavar, Manjunath/0000-0002-8871-5072
FU Norad; Laerdal Foundation; Eunice Kennedy Shriver National Institute of
Child Health and Human Development (NICHD)
FX The study was funded by grants from Norad, Laerdal Foundation and the
Eunice Kennedy Shriver National Institute of Child Health and Human
Development (NICHD). NICHD staff had input into the study design, data
interpretation and writing of the report. RTI staff had access to all
the study data. The corresponding author wrote the first draft of the
manuscript and had final responsibility for the decision to submit for
publication.
NR 17
TC 1
Z9 1
U1 6
U2 6
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2393
J9 BMC PREGNANCY CHILDB
JI BMC Pregnancy Childbirth
PD AUG 15
PY 2016
VL 16
AR 222
DI 10.1186/s12884-016-0997-6
PG 10
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA DT4UL
UT WOS:000381476500001
PM 27527831
ER
PT J
AU Gerfen, CR
Sawchenko, PE
AF Gerfen, Charles R.
Sawchenko, Paul E.
TI An anterograde neuroanatomical tracing method that shows the detailed
morphology of neurons, their axons and terminals: Immunohistochemical
localization of an axonally transported plant lectin, Phaseolus
vulgaris-leucoagglutinin (PHA-L)
SO BRAIN RESEARCH
LA English
DT Review
DE Neuroanatomy; Axonal tract tracing
ID CENTRAL-NERVOUS-SYSTEM; NEUROENDOCRINE STRESS-RESPONSE; SUPRAOPTIC
NUCLEI; NEURAL CIRCUITS; ORGANIZATION; HYPOTHALAMUS; INHIBITION; INPUTS;
BRAIN; RAT
AB A new neuroanatomical method for tracing connections in the central nervous system based on the anterograde axonal transport of the kidney bean lectin, Phaseolus vulgaris-leucoagglutinin (PHA-L) is described. The method, for which a detailed protocol is presented, offers several advantages over present techniques. First, when the lectin is delivered iontophoretically, PHA-L injection sites as small as 50200 mu m in diameter can be produced, and are clearly demarcated since the neurons within the labeled zone are completely filled. Second, many morphological features of such filled neurons are clearly demonstrated including their cell bodies, axons, dendritic arbors and even dendritic spines. Third, there is some evidence to suggest that only the neurons at the injection site that are filled transport demonstrable amounts of the tracer, raising the possibility that the effective injection site can be defined quite precisely. Fourth, even with the most restricted injections, the morphology of the labeled axons and axon terminals is clearly demonstrated; this includes boutons en passant, fine collateral branches, and various terminal specialization, all of which can be visualized as well as in the best rapid Golgi preparations. Fifth, when introduced iontophoretically, PHA-L appears to be transported preferentially in the anterograde direction; only rarely is it transported retrogradely. Sixth, PHA-L does not appear to be taken up and transported effectively by fibers of passage. Seventh, there is no discernible degradation of the transported PHA-L with survival times of up to 17 days. Finally, since the transported marker can be demonstrated with either peroxidase or fluorescent antibody techniques, it may be used in conjunction with other neuroanatomical methods. For example, double anterograde labeling experiments can be done using the autoradiographic method along with immunoperoxidase localization of PHA-L, and the retrogradely transported fluorescent dyes can be visualized in the same tissue sections as PHA-L localized with immunofluorescence techniques. 1984.
This article is part of a Special Issue entitled SI:50th Anniversary Issue. Published by Elsevier B.V.
C1 [Gerfen, Charles R.] NIMH, Lab Syst Neurosci, Bethesda, MD 20892 USA.
[Sawchenko, Paul E.] Salk Inst Biol Studies, Lab Neuronal Struct & Funct, La Jolla, CA USA.
RP Gerfen, CR (reprint author), NIMH, Lab Syst Neurosci, Bethesda, MD 20892 USA.
EM gerfenc@mail.nih.gov
NR 19
TC 1
Z9 1
U1 3
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 AUG 15
PY 2016
VL 1645
SI SI
BP 42
EP 45
DI 10.1016/j.brainres.2015.12.040
PG 4
WC Neurosciences
SC Neurosciences & Neurology
GA DT5QJ
UT WOS:000381537400014
PM 26790346
ER
PT J
AU Madlala, P
Singh, R
An, P
Werner, L
Mlisana, K
Karim, SSA
Winkler, CA
Ndung'u, T
AF Madlala, Paradise
Singh, Ravesh
An, Ping
Werner, Lise
Mlisana, Koleka
Karim, Salim S. Abdool
Winkler, Cheryl A.
Ndung'u, Thumbi
TI Association of Polymorphisms in the Regulatory Region of the Cyclophilin
a Gene (PPIA) with Gene Expression and HIV/AIDS Disease Progression
SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
LA English
DT Article
DE SNP; CypA; PPIA; HIV-1; mRNA expression
ID HIV-1 INFECTION; SUSCEPTIBILITY; DETERMINANTS; VIRIONS
AB Background:Human cyclophilin A (CypA) encoded by peptidyl prolyl isomerase A gene (PPIA), enhances HIV-1 replication by aiding capsid uncoating. The association of genetic variation in the PPIA regulatory region with susceptibility to HIV-1 infection, disease progression, and gene expression among black South Africans at risk for infection or infected with HIV-1 is unknown.Methods:We genotyped 539 participants from 2 longitudinal study cohorts of black South Africans at high risk for infection or infected with HIV-1 for PPIA regulatory single nucleotide polymorphisms by polymerase chain reaction-restriction fragment length polymorphism.Results:Minor allele (G) of SNP rs6850 (rs6850 G) significantly associated with higher viral loads (mean 4.85 versus 4.46 log copies/mL, P = 0.0006) and lower CD4(+) T-cell counts (mean 506 versus 557 cells/L, P = 0.0256) during the acute phase of infection in the Centre for the AIDS Programme of Research in South Africa (CAPRISA) 002 cohort. Consistently, rs6850 G significantly associated with higher viral loads (mean 4.49 versus 4.01 log copies/mL, P < 0.0001) and lower CD4(+) T-cell counts (mean 442 versus 494 cells/L, P = 0.0002) during the early chronic phase of infection in the CAPRISA 002 cohort; rs6850 G further associated significantly with rapid CD4(+) T-cell decline in the CAPRISA 002 cohort (P = 0.0481) and Sinikithemba chronic infection cohort (P = 0.0156). Interestingly, rs6850 G significantly associated with elevated CypA mRNA levels in HIV-1-positive individuals (P = 0.0061).Conclusions:These data suggest that rs6850 G enhances HIV-1 replication through upregulation of CypA expression following HIV-1 infection. The data support ongoing efforts to develop anti-HIV-1 drugs that block interaction of HIV-1 and cellular proteins.
C1 [Madlala, Paradise; Singh, Ravesh; Ndung'u, Thumbi] Univ KwaZulu Natal, Nelson R Mandela Sch Med, HIV Pathogenesis Programme, Durban, South Africa.
[Werner, Lise; Mlisana, Koleka; Karim, Salim S. Abdool] Univ KwaZulu Natal, Ctr AIDS Programme Res South Africa CAPRISA, Nelson R Mandela Sch Med, Durban, South Africa.
[An, Ping; Winkler, Cheryl A.] NCI, Basic Res Lab, Ctr Canc Res, Leidos Biomed Res Inc,Frederick Natl Lab Canc Res, Frederick, MD 21701 USA.
[Ndung'u, Thumbi] Univ KwaZulu Natal, KwaZulu Natal Res Inst TB & HIV, Nelson R Mandela Sch Med, Durban, South Africa.
RP Ndung'u, T (reprint author), Univ KwaZulu Natal, HIV Pathogenesis Programme, Doris Duke Med Res Inst, Nelson R Mandela Sch Med, Level 1,Room 117, ZA-4013 Durban, South Africa.
EM ndungu@ukzn.ac.za
OI Abdool Karim, Salim/0000-0002-4986-2133
FU seventh framework programme (FP7) of the European Commission (THINC)
[HEALTH-F3-2008-201032]; South African Department of Science and
Technology/National Research Foundation Research Chairs Initiative;
Victor Daitz Foundation; Howard Hughes Medical Institute International
Early Career Scientist award; National Cancer Institute, National
Institutes of Health [HHSN261200800001E]; Intramural Research Program of
the NIH, National Cancer Institute, Center for Cancer Research
FX Supported by the seventh framework programme (FP7) of the European
Commission (THINC, HEALTH-F3-2008-201032). Additional funding was
provided by the South African Department of Science and
Technology/National Research Foundation Research Chairs Initiative and
the Victor Daitz Foundation. Part of the work was funded by the Howard
Hughes Medical Institute International Early Career Scientist award to
TN. This project has been funded in part with federal funds from the
National Cancer Institute, National Institutes of Health, under contract
HHSN261200800001E. This Research was supported in part by the Intramural
Research Program of the 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 mention of trade names, commercial products, or
organizations imply endorsement by the US Government.
NR 22
TC 0
Z9 0
U1 1
U2 1
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 AUG 15
PY 2016
VL 72
IS 5
BP 465
EP 473
DI 10.1097/QAI.0000000000001028
PG 9
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA DT3KC
UT WOS:000381378700002
PM 27088296
ER
PT J
AU Smith, SJ
Pauly, GT
Akram, A
Melody, K
Ambrose, Z
Schneider, JP
Hughes, SH
AF Smith, Steven J.
Pauly, Gary T.
Akram, Aamir
Melody, Kevin
Ambrose, Zandrea
Schneider, Joel P.
Hughes, Stephen H.
TI Rilpivirine and Doravirine Have Complementary Efficacies Against
NNRTI-Resistant HIV-1 Mutants
SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
LA English
DT Article
DE HIV-1; antiviral activity; susceptibility; potency; resistance;
non-nucleoside reverse transcriptase inhibitor
ID REVERSE-TRANSCRIPTASE INHIBITORS; NONNUCLEOSIDE INHIBITORS; POSITIONAL
ADAPTABILITY; HIV-1-INFECTED PATIENTS; DOUBLE-BLIND; WILD-TYPE; DRUG;
MECHANISM; PHASE-3; TMC278
AB Background:Rilpivirine (RPV) is the latest non-nucleoside reverse transcriptase inhibitor (NNRTI) to be approved by Food and Drug Administration to combat HIV-1 infections. NNRTIs inhibit the chemical step in viral DNA synthesis by binding to an allosteric site located about 10 angstrom from the polymerase active site of reverse transcriptase (RT). Although NNRTIs potently inhibit the replication of wild-type HIV-1, the binding site is not conserved, and mutations arise in the binding pocket. Doravirine (DOR) is a new NNRTI in phase III clinical trials.Methods:Using a single round HIV-1 infection assay, we tested RPV and DOR against a broad panel of NNRTI-resistant mutants to determine their respective activities. We also used molecular modeling to determine if the susceptibility profile of each compound was related to how they bind RT.Results:Several mutants displayed decreased susceptibility to DOR. However, with the exception of E138K, our data suggest that the mutations that reduce the potency of DOR and RPV are non-overlapping. Thus, these 2 NNRTIs have the potential to be used together in combination therapy. We also show that the location at which DOR and RPV bind with the NNRTI binding pocket of RT correlates with the differences in their respective susceptibility to the panel of NNRTI-resistance mutations.Conclusions:This shows that (1) DOR is susceptible to a number of well-known NNRTI resistance mutations and (2) an understanding of the mutational susceptibilities and binding interactions of NNRTIs with RT could be used to develop pairs of compounds with non-overlapping mutational susceptibilities.
C1 [Smith, Steven J.; Akram, Aamir; Hughes, Stephen H.] NCI, HIV Dynam & Replicat Program, NIH, POB B 1050 Boyles St,539-130, Frederick, MD 21702 USA.
[Pauly, Gary T.; Schneider, Joel P.] NCI, Biol Chem Lab, NIH, Frederick, MD 21701 USA.
[Melody, Kevin; Ambrose, Zandrea] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Infect Dis & Microbiol, Pittsburgh, PA 15261 USA.
[Ambrose, Zandrea] Univ Pittsburgh, Sch Med, Dept Med, Div Infect Dis, Pittsburgh, PA 15213 USA.
RP Hughes, SH (reprint author), NCI, HIV Dynam & Replicat Program, NIH, POB B 1050 Boyles St,539-130, Frederick, MD 21702 USA.
EM hughesst@mail.nih.gov
FU Intramural Research Programs of the National Cancer Institute;
Intramural AIDS Targeted Antiviral Program (IATAP); NIH [R01 AI080290,
T32 AI065380]
FX Supported by the Intramural Research Programs of the National Cancer
Institute and the Intramural AIDS Targeted Antiviral Program (IATAP) and
NIH grants R01 AI080290 (Z.A.) and T32 AI065380 (K.M.).
NR 27
TC 0
Z9 0
U1 3
U2 3
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 AUG 15
PY 2016
VL 72
IS 5
BP 485
EP 491
DI 10.1097/QAI.0000000000001031
PG 7
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA DT3KC
UT WOS:000381378700004
PM 27124362
ER
PT J
AU Huang, B
Wang, Q
Deng, CS
Wang, JH
Yang, T
Huang, SG
Su, XZ
Liu, YJ
Pan, LH
Li, GM
Li, D
Zhang, HY
Bacar, A
Abdallah, KS
Attoumane, R
Mliva, AMSA
Zheng, SQ
Xu, Q
Lu, FL
Guan, YZ
Song, JP
AF Huang, Bo
Wang, Qi
Deng, Changsheng
Wang, Jianhua
Yang, Tao
Huang, Shiguang
Su, Xin-zhuan
Liu, Yajun
Pan, Longhua
Li, Guoming
Li, Di
Zhang, Hongying
Bacar, Afane
Abdallah, Kamal Said
Attoumane, Rachad
Mliva, Ahamada M. S. A.
Zheng, Shaoqin
Xu, Qin
Lu, Fangli
Guan, Yezhi
Song, Jianping
TI Prevalence of crt and mdr-1 mutations in Plasmodium falciparum isolates
from Grande Comore island after withdrawal of chloroquine
SO MALARIA JOURNAL
LA English
DT Article
DE Comoros; Plasmodium falciparum; Chloroquine resistance; pfcrt; pfmdr-1
ID GENE HAPLOTYPE SVMNT; DRUG-RESISTANCE; ARTEMETHER-LUMEFANTRINE;
MOLECULAR MARKER; TRANSPORTER GENE; TREATMENT POLICY; COPY NUMBER;
IN-VIVO; MALARIA; PFCRT
AB Background: In Comoros, the widespread of chloroquine (CQ)-resistant Plasmodium falciparum populations was a major obstacle to malaria control, which led to the official withdrawal of CQ in 2004. Continuous monitoring of CQ-resistant markers of the P. falciparum CQ resistant transporter (pfcrt) and the P. falciparum multiple drug resistance 1 (pfmdr-1) is necessary inder to obtain first-hand information on CQ susceptibility of parasite populations in the field. The objective of this study is to assess the prevalence and evolution of CQ-resistance in the P. falciparum populations on the Comoros' Grande Comore island after withdrawal of CQ.
Methods: A total of 207 P. falciparum clinical isolates were collected from the island, including 118 samples from 2006 to 2007 and 89 samples from 2013 to 2014. Nucleotide substitutions in the pfcrt and pfmdr-1 genes linked to CQ response in parasite isolates were assessed using nested PCR and DNA sequencing.
Results: From the pfcrt gene segment sequenced, we detected C72S, M74I, N75E, and K76T substitutions in the parasite isolates collected from both 2006-2007 to 2013-2014 periods. Significant decline of pfcrt resistant alleles at C72S (42.6 to 6.9 %), M74I (39.1 to 14.9 %), N75E (63.5 to 18.3 %), and K76T (72.2 to 19.5 %) from 2006-2007 to 2013-2014 were observed, and the frequency of pfcrt wild type allele was significantly increased from 19.1 % in 2006-2007 to 75.8 % in 2013-2014. Sequence analysis of pfmdr-1 also detected point mutations at codons N86Y, Y184F, and D1246Y, but not S1034C and N1042D, in the isolates collected from both examined periods. An increasing trend in the prevalence of the pfmdr-1 wild type allele (NYD, 4.3 % in 2006-2007; and 28.7 % in 2013-2014), and a decreasing trend for pfmdr-1 N86Y mutation (87.0 % in 2006-2007; and 40.2 % in 2013-2014) were observed in our samples.
Conclusions: The present data indicate that the prevalence and patterns of mutant pfcrt and pfmdr-1 dramatically decreased in the Grande Comore isolates from 2006 to 2014, suggesting that the CQ-sensitive P. falciparum strains have returned after the withdrawal of CQ. The data also suggests that the parasites with wild type pfcrt/pfdmr-1 genes may have growth and/or transmission advantages over the mutant parasites. The information obtained from this study will be useful for developing and updating anti-malarial treatment policy in Grande Comore island.
C1 [Huang, Bo; Wang, Qi; Deng, Changsheng; Wang, Jianhua; Yang, Tao; Zhang, Hongying; Zheng, Shaoqin; Guan, Yezhi; Song, Jianping] Guangzhou Univ Chinese Med, Sci & Technol Pk, Guangzhou 510006, Guangdong, Peoples R China.
[Huang, Shiguang] Jinan Univ, Sch Med, Guangzhou 510632, Guangdong, Peoples R China.
[Su, Xin-zhuan] NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA.
[Su, Xin-zhuan] Xiamen Univ, Sch Life Sci, State Key Lab Cellular Stress Biol, Xiamen 361005, Fujian, Peoples R China.
[Liu, Yajun] Guangzhou Univ Chinese Med, Affiliated Hosp 1, Guangzhou 510006, Guangdong, Peoples R China.
[Pan, Longhua; Li, Guoming; Li, Di] Guangdong Newsouth Artepharm Co Ltd, Guangzhou 510405, Guangdong, Peoples R China.
[Bacar, Afane; Abdallah, Kamal Said; Attoumane, Rachad] Natl Malaria Control Programme, BP 500 Moroni, Moroni, Comoros.
[Mliva, Ahamada M. S. A.] Minist Hlth Comoros, BP 500 Moroni, Moroni, Comoros.
[Xu, Qin] Guangzhou Univ Chinese Med, Res Inst Trop Med, Guangzhou 510006, Guangdong, Peoples R China.
[Lu, Fangli] Sun Yat Sen Univ, Zhongshan Sch Med, Dept Parasitol, Guangzhou 510080, Guangdong, Peoples R China.
RP Guan, YZ; Song, JP (reprint author), Guangzhou Univ Chinese Med, Sci & Technol Pk, Guangzhou 510006, Guangdong, Peoples R China.
EM gyz111@hotmail.com; songjpgz@sina.com
OI Su, Xinzhuan/0000-0003-3246-3248
FU Natural Science Foundation of China [81273643]; Guangdong Provincial
Science and Technology Program [2014B050502013]; China Postdoctoral
Science Foundation [2015M570699, 2016T90773]; Guangdong Provincial
Science Foundation [2015A030310107]; Guangdong Provincial Medicine
Science Foundation [A2016315]; Foundation of Traditional Chinese
Medicine Bureau of Guangdong Province [20141074]; Science and Technology
Program of Guangzhou [2014J4500037]; Division of Intramural Research,
National Institute of Allergy and Infectious Diseases, National
Institutes of Health
FX This work was supported in part by grants from Natural Science
Foundation of China [Grant Number 81273643] and Guangdong Provincial
Science and Technology Program [Grant Number 2014B050502013] to JS,
China Postdoctoral Science Foundation [Grant Number 2015M570699 and
2016T90773], Guangdong Provincial Science Foundation [Grant Number
2015A030310107], and Guangdong Provincial Medicine Science Foundation
[Grant Number A2016315] to BH, Foundation of Traditional Chinese
Medicine Bureau of Guangdong Province [Grant Number 20141074] to QW,
Science and Technology Program of Guangzhou [2014J4500037] to YG, and by
the Division of Intramural Research, National Institute of Allergy and
Infectious Diseases, National Institutes of Health (XzS). The funds had
no role in the study design, data collection and analysis, decision to
publish, or the preparation of the manuscript.
NR 52
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U2 3
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1475-2875
J9 MALARIA J
JI Malar. J.
PD AUG 15
PY 2016
VL 15
AR 414
DI 10.1186/s12936-016-1474-4
PG 9
WC Infectious Diseases; Parasitology; Tropical Medicine
SC Infectious Diseases; Parasitology; Tropical Medicine
GA DT3CQ
UT WOS:000381358500004
PM 27527604
ER
PT J
AU Wu, SP
Pfeiffer, RM
Ahn, IE
Mailankody, S
Sonneveld, P
van Duin, M
Munshi, NC
Walker, BA
Morgan, G
Landgren, O
AF Wu, S. Peter
Pfeiffer, Ruth M.
Ahn, Inhye E.
Mailankody, Sham
Sonneveld, Pieter
van Duin, Mark
Munshi, Nikhil C.
Walker, Brian A.
Morgan, Gareth
Landgren, Ola
TI Impact of Genes Highly Correlated with MMSET Myeloma on the Survival of
Non-MMSET Myeloma Patients
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID RISK MULTIPLE-MYELOMA; BREAST-CANCER RISK; T(4/14) MYELOMA; CELL-CYCLE;
C-MYC; PLASMA-CELLS; EXPRESSION; PREDICTION; TRANSLOCATION; TRANSCRIPTS
AB Purpose: The poor prognosis of multiple myeloma with t(4;14) is driven by the fusion of genes encoding multiple myeloma SET domain (MMSET) and immunoglobulin heavy chain. Specific genes affected by MMSET and their clinical implications in non-MMSET myeloma remain undetermined.
Experimental Design: We obtained gene expression profiles of 1,032 newly diagnosed myeloma patients enrolled in Total Therapy 2, Total Therapy 3, Myeloma IX, and HOVON65-GMMGHD4 trials and 156 patients from Multiple Myeloma Resource Collection. Probes that correlated most with MMSET myeloma were selected on the basis of a multivariable linear regression and Bonferroni correction and refined on the basis of the strength of association with survival in non-MMSET patients.
Results: Ten MMSET-like probes were associated with poor survival in non-MMSET myeloma. Non-MMSET myeloma patients in the highest quartile of the 10-gene signature (MMSET-like myeloma) had 5-year overall survival similar to that of MMSET myeloma [highest quartile vs. lowest quartile HR = 2.0; 95% confidence interval (CI), 1.5-2.8 in MMSET-like myeloma; HR = 2.3; 95% CI, 1.6-3.3 in MMSET myeloma]. Analyses of MMSET-like gene signature suggested the involvement of p53 and MYC pathways.
Conclusions: MMSET-like gene signature captures a subset of high-risk myeloma patients underrepresented by conventional risk stratification platforms and defines a distinct biologic subtype. (C) 2016 AACR.
C1 [Wu, S. Peter; Ahn, Inhye E.] NCI, Multiple Myeloma Sect, NIH, Bethesda, MD 20892 USA.
[Pfeiffer, Ruth M.] NCI, Dept Canc Epidemiol & Genet, Biostat Branch, NIH, Rockville, MD USA.
[Mailankody, Sham; Landgren, Ola] Mem Sloan Kettering Canc Ctr, Myeloma Serv, New York, NY 10021 USA.
[Sonneveld, Pieter; van Duin, Mark] Erasmus Univ, Med Ctr, Dept Hematol, Rotterdam, Netherlands.
[Munshi, Nikhil C.] Harvard Med Sch, Lebow Inst Myeloma Therapeut, Boston, MA USA.
[Munshi, Nikhil C.] Harvard Med Sch, Jerome Lipper Multiple Myeloma Ctr, Dana Farber Canc Inst, Boston, MA USA.
[Walker, Brian A.] Inst Canc Res, Sect Haematooncol, London, England.
[Morgan, Gareth] Univ Arkansas Med Sci, Myeloma Inst Res & Therapy, Little Rock, AR 72205 USA.
RP Landgren, O (reprint author), Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10065 USA.
EM landgrec@mskcc.org
OI Walker, Brian/0000-0002-8615-6254
FU NIH; NIH Medical Research Scholars Program
FX This work was supported by the intramural research program of the NIH.
Research support for S.P. Wu was made possible through the NIH 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 Leona M. and Harry B. Helmsley Charitable
Trust, and the Howard Hughes Medical Institute, as well as other private
donors. For a complete list, please visit the Foundation website at
http://www.fnih.org/work/programs-development/medical-research-scholars-
program.
NR 35
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U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
EI 1557-3265
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD AUG 15
PY 2016
VL 22
IS 16
BP 4039
EP 4044
DI 10.1158/1078-0432.CCR-15-2366
PG 6
WC Oncology
SC Oncology
GA DU5QH
UT WOS:000382265900009
PM 26847058
ER
PT J
AU Osgood, CL
Maloney, N
Kidd, CG
Kitchen-Goosen, S
Segars, L
Gebregiorgis, M
Woldemichael, GM
He, M
Sankar, S
Lessnick, SL
Kang, M
Smith, M
Turner, L
Madaj, ZB
Winn, ME
Nunez, LE
Gonzalez-Sabin, J
Helman, LJ
Moris, F
Grohar, PJ
AF Osgood, Christy L.
Maloney, Nichole
Kidd, Christopher G.
Kitchen-Goosen, Susan
Segars, Laura
Gebregiorgis, Meti
Woldemichael, Girma M.
He, Min
Sankar, Savita
Lessnick, Stephen L.
Kang, Min
Smith, Malcolm
Turner, Lisa
Madaj, Zachary B.
Winn, Mary E.
Nunez, Luz-Elena
Gonzalez-Sabin, Javier
Helman, Lee J.
Moris, Francisco
Grohar, Patrick J.
TI Identification of Mithramycin Analogues with Improved Targeting of the
EWS-FLI1 Transcription Factor
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID CHILDRENS ONCOLOGY GROUP; LOCALIZED EWING SARCOMA; IN-VIVO;
COMBINATORIAL BIOSYNTHESIS; ONCOGENIC TRANSCRIPTION; NEUROECTODERMAL
TUMOR; ANTITUMOR-ACTIVITY; GENE-EXPRESSION; GROWTH; EWS/FLI
AB Purpose: The goal of this study was to identify second-generation mithramycin analogues that better target the EWS-FLI1 transcription factor for Ewing sarcoma. We previously established mithramycin as an EWS-FLI1 inhibitor, but the compound's toxicity prevented its use at effective concentrations in patients.
Experimental Design: We screened a panel of mithralogs to establish their ability to inhibit EWS-FLI1 in Ewing sarcoma. We compared the IC50 with the MTD established in mice to determine the relationship between efficacy and toxicity. We confirmed the suppression of EWS-FLI1 at the promoter, mRNA, gene signature, and protein levels. We established an improved therapeutic window by using time-lapse microscopy to model the effects on cellular proliferation in Ewing sarcoma cells relative to HepG2 control cells. Finally, we established an improved therapeutic window using a xenograft model of Ewing sarcoma.
Results: EC-8105 was found to be the most potent analogue and was able to suppress EWS-FLI1 activity at concentrations nontoxic to other cell types. EC-8042 was substantially less toxic than mithramycin in multiple species but maintained suppression of EWS-FLI1 at similar concentrations. Both compounds markedly suppressed Ewing sarcoma xenograft growth and inhibited EWS-FLI1 in vivo.
Conclusions: These results provide a basis for the continued development of EC-8042 and EC-8105 as EWS-FLI1 inhibitors for the clinic. (C) 2016 AACR.
C1 [Osgood, Christy L.; Maloney, Nichole; Kidd, Christopher G.; Segars, Laura; Grohar, Patrick J.] Vanderbilt Univ, Sch Med, Div Pediat Hematol Oncol, Nashville, TN 37212 USA.
[Kitchen-Goosen, Susan; Turner, Lisa; Madaj, Zachary B.; Winn, Mary E.; Grohar, Patrick J.] Van Andel Res Inst, 333 Bostwick Ave NE, Grand Rapids, MI 49503 USA.
[Segars, Laura; Gebregiorgis, Meti; Smith, Malcolm; Helman, Lee J.] NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA.
[Woldemichael, Girma M.] Frederick Natl Lab Canc Res, Basic Sci Program, Leidos Biomed Res Lab Inc, Mol Targets Lab, Frederick, MD USA.
[He, Min; Smith, Malcolm] NCI, Dev Therapeut Program, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA.
[Sankar, Savita] Washington Univ, Sch Med, Dept Dev Biol, St Louis, MO USA.
[Lessnick, Stephen L.] Ohio State Univ, Nationwide Childrens Hosp, Div Pediat Hematol Oncol BMT, Ctr Childhood Canc & Blood Disorders, Columbus, OH 43210 USA.
[Kang, Min] Texas Tech Univ, Hlth Sci Ctr, Sch Med, Lubbock, TX 79430 USA.
[Nunez, Luz-Elena; Gonzalez-Sabin, Javier; Moris, Francisco] EntreChem SL, Oviedo, Spain.
[Grohar, Patrick J.] Helen De Vos Childrens Hosp, Grand Rapids, MI USA.
[Grohar, Patrick J.] Michigan State Univ, Sch Med, Dept Pediat, E Lansing, MI 48824 USA.
RP Grohar, PJ (reprint author), Van Andel Res Inst, 333 Bostwick Ave NE, Grand Rapids, MI 49503 USA.
EM patrick.grohar@vai.org
FU Hyundai Hope on Wheels Program; T32 training grant; Vanderbilt Clinical
Oncology Research Career Development K12; Vanderbilt University
Department of Pediatrics; Lily's Garden Foundation; Frederick National
Laboratory for Cancer Research, National Institutes of Health
[HHSN261200800001E]
FX The majority of the funding for this work was from the Hyundai Hope on
Wheels Program (to P.J. Grohar, C.G. Kidd, and N. Maloney). Funding was
also provided by the T32 training grant conducting research in pediatric
oncology (Principal Investigator, D. Friedman) as well as the Vanderbilt
Clinical Oncology Research Career Development K12 both for C.L. Osgood
(Principal Investigator, D. Friedman). Additional internal funds were
provided by the Vanderbilt University Department of Pediatrics (to P.J.
Grohar, C.L. Osgood, and N. Maloney). Immunofluorescent assay
development was supported by the Alex's Lemonade Stand Reach Award (to
P.J. Grohar). Additional funding was provided by the Lily's Garden
Foundation (to P.J. Grohar and L. Segars). EntreChem thanks Mariam
Hermosilla and Patricia Oro for superior technical assistance. This
project has also been funded in part with federal funds from the
Frederick National Laboratory for Cancer Research, National Institutes
of Health under contract HHSN261200800001E (to G.M. Woldemichael).
NR 49
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U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
EI 1557-3265
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD AUG 15
PY 2016
VL 22
IS 16
BP 4105
EP 4118
DI 10.1158/1078-0432.CCR-15-2624
PG 14
WC Oncology
SC Oncology
GA DU5QH
UT WOS:000382265900016
PM 26979396
ER
PT J
AU Dellibovi-Ragheb, T
Altan-Bonnet, N
AF Dellibovi-Ragheb, Teegan
Altan-Bonnet, Nihal
TI Cloud storage for endosomes
SO EMBO JOURNAL
LA English
DT Editorial Material
AB Coordinated regulation of vesicle trafficking is critical for the proper functioning of a cell. The bulk of cellular transport vesicles are sequestered in a "perinuclear cloud", with only a small fraction released to the cell periphery. Jongsma et al (2016) found that the ER-associated E3 ubiquitin ligase RNF26 is responsible for establishing and maintaining the architecture of the perinuclear cloud and that this spatiotemporal positioning is critical for effective regulation of the endocytic and exocytic systems.
C1 [Dellibovi-Ragheb, Teegan; Altan-Bonnet, Nihal] NHLBI, Lab Host Pathogen Dynam, Cell Biol & Physiol Ctr, NIH, Bldg 10, Bethesda, MD 20892 USA.
RP Altan-Bonnet, N (reprint author), NHLBI, Lab Host Pathogen Dynam, Cell Biol & Physiol Ctr, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM nihal.altan-bonnet@nih.gov
NR 7
TC 0
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U1 1
U2 1
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 AUG 15
PY 2016
VL 35
IS 16
BP 1724
EP 1725
DI 10.15252/embj.201695080
PG 2
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA DU6II
UT WOS:000382317500002
PM 27378788
ER
PT J
AU Kehrl, JH
AF Kehrl, John H.
TI The impact of RGS and other G-protein regulatory proteins on G
alpha(i)-mediated signaling in immunity
SO BIOCHEMICAL PHARMACOLOGY
LA English
DT Review
DE G-protein; RGS proteins; Chemokine receptors; Sphingosine 1-phosphate;
Cell trafficking
ID G-ALPHA-I; HETEROTRIMERIC G-PROTEINS; RECEPTOR-INDEPENDENT ACTIVATORS;
T-LYMPHOCYTE MIGRATION; ELEGANS NERVOUS-SYSTEM; G-BETA-GAMMA; NEUTROPHIL
CHEMOTAXIS; PERTUSSIS-TOXIN; COUPLED RECEPTORS; CELL-DIVISION
AB Leukocyte chemoattractant receptors are members of the G-protein coupled receptor (GPCR) family. Signaling downstream of these receptors directs the localization, positioning and homeostatic trafficking of leukocytes; as well as their recruitment to, and their retention at, inflammatory sites. Ligand induced changes in the molecular conformation of chemoattractant receptors results in the engagement of heterotrimeric G-proteins, which promotes alpha subunits to undergo GTP/GDP exchange. This results in the functional release of B gamma subunits from the heterotrimers, thereby activating downstream effector molecules, which initiate leukocyte polarization, gradient sensing, and directional migration. Pertussis toxin ADP ribosylates G alpha(i) subunits and prevents chemoattractant receptors from triggering G alpha(i) nucleotide exchange. The use of pertussis toxin revealed the essential importance of G alpha(i) subunit nucleotide exchange for chemoattractant receptor signaling. More recent studies have identified a range of regulatory mechanisms that target these receptors and their associated heterotrimeric G-proteins, thereby helping to control the magnitude, kinetics, and duration of signaling. A failure in these regulatory pathways can lead to impaired receptor signaling and immunopathology. The analysis of mice with targeted deletions of G alpha(i) isoforms as well as some of these G-protein regulatory proteins is providing insights into their roles in chemoattractant receptor signaling. Published by Elsevier Inc.
C1 [Kehrl, John H.] NIAID, Immunoregulat Lab, NIH, Bldg 10,Room 11B08,10 Ctr Dr MSC 1876, Bethesda, MD 20892 USA.
RP Kehrl, JH (reprint author), NIAID, Immunoregulat Lab, NIH, Bldg 10,Room 11B08,10 Ctr Dr MSC 1876, Bethesda, MD 20892 USA.
EM jkehrl@niaid.nih.gov
FU intramural program of the National Institutes of Allergy and Infectious
Diseases
FX The author would like to thank the members of his laboratory that
contributed to some of the studies described in this review and thank
Dr. Anthony Fauci for his long standing support. The intramural program
of the National Institutes of Allergy and Infectious Diseases supported
some of the research described in this review.
NR 154
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U2 8
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0006-2952
EI 1873-2968
J9 BIOCHEM PHARMACOL
JI Biochem. Pharmacol.
PD AUG 15
PY 2016
VL 114
SI SI
BP 40
EP 52
DI 10.1016/j.bcp.2016.04.005
PG 13
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA DT1KK
UT WOS:000381241000005
PM 27071343
ER
PT J
AU Kersey, RK
Brodigan, TM
Fukushige, T
Krause, MW
AF Kersey, Rossio K.
Brodigan, Thomas M.
Fukushige, Tetsunari
Krause, Michael W.
TI Regulation of UNC-130/FOXD-mediated mesodermal patterning in C-elegans
SO DEVELOPMENTAL BIOLOGY
LA English
DT Article
DE Forkhead; FOXD; UNC-130; UNC-129; Embryogenesis; Transcriptional
regulation
ID FORKHEAD TRANSCRIPTION FACTORS; CAENORHABDITIS-ELEGANS; DNA-BINDING;
GENETIC INTERFERENCE; MUSCLE DEVELOPMENT; FEEDBACK LOOP; BOX PROTEINS;
TGF-BETA; EXPRESSION; GENOME
AB Spatial polarity cues in animals are used repeatedly during development for many processes, including cell fate determination, cell migration, and axon guidance. In Caenorhabditis elegans, the body wall muscle extends the length of the animal in four distinct quadrants and generates an UNC-129/TGF-beta-related signal that is much higher in the dorsal two muscle quadrants compared to their ventral counterparts. This pattern of unc-129 expression requires the activity of the proposed transcriptional repressor UNC-130/FOXD whose body wall muscle activity is restricted to the ventral two body wall muscle quadrants. To understand how these dorsal-ventral differences in UNC-130 activity are established and maintained, we have analyzed the regulation of unc-130 expression and the distribution of UNC-130 protein. We have identified widespread, cis-acting elements in the unc-130 promoter that function to positively regulate ventral body wall muscle expression and negatively regulate dorsal body wall muscle expression. We have defined the temporal distribution of UNC-130 protein in body wall muscle cells during embryogenesis, demonstrated that this pattern is required to establish the dorsal-ventral polarity of UNC-129/TGF-beta, and shown that UNC-130 is not required post-embryonically to maintain the asymmetry of body wall muscle unc-129 expression. Finally, we have tested the impact of the depletion of a variety of transcription factors, repressors, and signaling molecules to identify additional regulators of body wall muscle UNC-130 polarity. Our results confirm and extend earlier studies to clarify the mechanisms by which UNC-130 is controlled and affects the pattern of unc-129 expression in body wall muscle. These results further our understanding of the transcriptional logic behind the generation of polarity cues involving this poorly understood subclass of Forkhead factors. Published by Elsevier Inc.
C1 [Kersey, Rossio K.; Brodigan, Thomas M.; Fukushige, Tetsunari; Krause, Michael W.] NIDDK, Mol Biol Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
RP Krause, MW (reprint author), NIDDK, Mol Biol Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM michaelkr@niddk.nih.gov
OI Krause, Michael/0000-0001-6127-3940
FU NIH Office of Research Infrastructure Programs [P40 OD010440];
Intramural Research Program of the NIH, The National Institute of
Diabetes and Digestive and Kidney Diseases (NIDDK)
FX Our thanks to Lyn Noordam for help with the text and figures, Andy
Golden, Harold Smith, and Jim McGhee for plasmids, Harald Hutter for
strains, Piali Sengupta and Michel Labouesse for antibodies, Jun "Kelly"
Liu for reagents and comments on the manuscript, Ward Odenwald for help
with EvoPrinter-based identifications of conserved promoter sequences,
and WormBase as a resource. Some strains were provided by the CGC, which
is funded by NIH Office of Research Infrastructure Programs (P40
OD010440). This work was supported by the Intramural Research Program of
the NIH, The National Institute of Diabetes and Digestive and Kidney
Diseases (NIDDK).
NR 51
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U2 4
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0012-1606
EI 1095-564X
J9 DEV BIOL
JI Dev. Biol.
PD AUG 15
PY 2016
VL 416
IS 2
BP 300
EP 311
DI 10.1016/j.ydbio.2016.06.029
PG 12
WC Developmental Biology
SC Developmental Biology
GA DT9QE
UT WOS:000381836600005
PM 27341757
ER
PT J
AU Peer, CJ
Strope, JD
Beedie, S
Ley, AM
Holly, A
Calis, K
Farkas, R
Parepally, J
Men, A
Fadiran, EO
Scott, P
Jenkins, M
Theodore, WH
Sissung, TM
AF Peer, Cody J.
Strope, Jonathan D.
Beedie, Shaunna
Ley, Ariel M.
Holly, Alesia
Calis, Karim
Farkas, Ronald
Parepally, Jagan
Men, Angela
Fadiran, Emmanuel O.
Scott, Pamela
Jenkins, Marjorie
Theodore, William H.
Sissung, Tristan M.
TI Alcohol and Aldehyde Dehydrogenases Contribute to Sex-Related
Differences in Clearance of Zolpidem in Rats
SO FRONTIERS IN PHARMACOLOGY
LA English
DT Article
DE zolpidem; drug metabolism; pharmacokinetics; testosterone
ID ETHANOL-METABOLISM; HUMAN LIVER; PHARMACOKINETICS; EXPRESSION;
MECHANISM; GENDER; BRAIN; MUCOSA; ADULTS; AGE
AB Objectives: The recommended zolpidem starting dose was lowered in females (5 mg vs. 10 mg) since side effects were more frequent and severe than those of males; the mechanism underlying sex differences in pharmacokinetics (PK) is unknown. We hypothesized that such differences were caused by known sex-related variability in alcohol dehydrogenase (ADH) expression.
Methods: Male, female, and castrated male rats were administered 2.6 mg/kg zolpidem, +/- disulfiram (ADH/ALDH pathway inhibitor) to compare PK changes induced by sex and gonadal hormones. PK analyses were conducted in rat plasma and rat brain.
Key findings: Sex differences in PK were evident: females had a higher C-MAX (112.4 vs. 68.1 ug/L) and AUG (537.8 vs. 231.8 h*ug/L) than uncastrated males. Castration induced an earlier T-MAX (0.25 vs. 1 h), greater C-MAX (109.1 vs. 68.1 ug/L), and a corresponding AUG increase (339.7 vs. 231.8 h*ug/L). Administration of disulfiram caused more drastic C-MAX and T-MAX changes in male vs. female rats that mirrored the effects of castration on first-pass metabolism, suggesting that the observed PK differences may be caused by ADH/ALDH expression. Brain concentrations paralleled plasma concentrations.
Conclusion: These findings indicate that sex differences in zolpidem PK are influenced by variation in the expression of ADH/ALDH due to gonadal androgens.
C1 [Peer, Cody J.; Sissung, Tristan M.] NCI, Clin Pharmacol Program, NIH, Bethesda, MD 20892 USA.
[Strope, Jonathan D.; Beedie, Shaunna; Ley, Ariel M.; Holly, Alesia] NCI, Mol Pharmacol Program, NIH, Bethesda, MD 20892 USA.
[Calis, Karim] Food & Drug Adm, Ctr Drug Evaluat & Res, Off Med Policy, Silver Spring, MD USA.
[Farkas, Ronald] Food & Drug Adm, Ctr Drug Evaluat & Res, Div Neurol Prod, Off New Drugs, Silver Spring, MD USA.
[Parepally, Jagan; Men, Angela] Food & Drug Adm, Ctr Drug Evaluat & Res, Off Translat Sci, Off Clin Pharmacol, Silver Spring, MD USA.
[Fadiran, Emmanuel O.; Scott, Pamela; Jenkins, Marjorie] Food & Drug Adm, Off Commissioner, Off Womens Hlth, Silver Spring, MD USA.
[Theodore, William H.] NINDS, Clin Epilepsy Sect, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
RP Sissung, TM (reprint author), NCI, Clin Pharmacol Program, NIH, Bethesda, MD 20892 USA.
EM sissungt@mail.nih.gov
FU National Cancer Institute (National Institutes of Health); Intramural
Research Program of the NIH, National Cancer Institute; Office of
Women's Health, Food, and Drug Administration; Food Drug Administration
FX This project has been funded in whole or in part with federal funds from
the National Cancer Institute (National Institutes of Health) and the
Food Drug Administration. This work was supported by the Intramural
Research Program of the NIH, National Cancer Institute, and the Office
of Women's Health, Food, and Drug Administration.
NR 44
TC 1
Z9 1
U1 3
U2 6
PU FRONTIERS MEDIA SA
PI LAUSANNE
PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015,
SWITZERLAND
SN 1663-9812
J9 FRONT PHARMACOL
JI Front. Pharmacol.
PD AUG 15
PY 2016
VL 7
AR 260
DI 10.3380/fphar.2016.00260
PG 9
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA DT2ZU
UT WOS:000381351100001
PM 27574509
ER
PT J
AU Lau, MWL
Ferre-D'Amare, AR
AF Lau, Matthew W. L.
Ferre-D'Amare, Adrian R.
TI In vitro evolution of coenzyme-independent variants from the glmS
ribozyme structural scaffold
SO METHODS
LA English
DT Article
DE SELEX; Catalytic RNA; Divalent cation; Riboswitch; Mercury-thiol
affinity chromatography
ID SMALL MOLECULES; INTERVENING SEQUENCE; GENE-EXPRESSION; RNA;
TETRAHYMENA; RIBOSWITCH; COFACTOR; BINDING; GLUCOSAMINE-6-PHOSPHATE;
TRANSCRIPTION
AB Uniquely among known natural ribozymes that cleave RNA sequence-specifically, the glmS ribozyme-riboswitch employs a small molecule, glucosamine-6-phosphate (GlcN6P) as a catalytic cofactor. In vitro selection was employed to search for coenzyme-independent variants of this ribozyme. In addition to shedding light on the catalytic mechanism of the ribozyme, such variants could resemble the evolutionary ancestors of the modern, GlcN6P-regulated ribozyme-riboswitch. A mutant pool was constructed such that the secondary structure elements, which define the triply-pseudoknotted global fold of the ribozyme, was preserved. A stringent selection scheme that relies on thiol-mercury affinity chromatography for separating active and inactive sequences ultimately yielded a triple mutant with a cleavage rate exceeding 3 min(-1) that only requires divalent cations for activity. Mutational analysis demonstrated that a point reversion of the variant toward the wild-type sequence was sufficient to partially restore GlcN6P-dependence, suggesting that coenzyme dependence can be readily be acquired by RNA5 that adopt the glmS ribozyme fold. The methods employed to perform this selection experiment are described in detail in this review. Published by Elsevier Inc.
C1 [Lau, Matthew W. L.; Ferre-D'Amare, Adrian R.] NHLBI, 50 South Dr,MSC 8012, Bethesda, MD 20892 USA.
RP Ferre-D'Amare, AR (reprint author), NHLBI, 50 South Dr,MSC 8012, Bethesda, MD 20892 USA.
EM adrian.ferre@nih.gov
FU Intramural Program of the National Heart, Lung and Blood Institute, NIH
FX We thank S. Bachas, N. Baird, M. Chen, J. Hogg, C. Jones, J. Posakony,
R. Trachman, K. Warner, and J. Zhang for discussions. M.W.L. was a
Croucher Foundation Postdoctoral Fellow. This work was supported in part
by the Intramural Program of the National Heart, Lung and Blood
Institute, NIH.
NR 41
TC 2
Z9 2
U1 5
U2 5
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1046-2023
EI 1095-9130
J9 METHODS
JI Methods
PD AUG 15
PY 2016
VL 106
BP 76
EP 81
DI 10.1016/j.ymeth.2016.04.027
PG 6
WC Biochemical Research Methods; Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA DT9PZ
UT WOS:000381836100011
PM 27130889
ER
PT J
AU Hoinka, J
Przytycka, T
AF Hoinka, Jan
Przytycka, Teresa
TI AptaPLEX - A dedicated, multithreaded demultiplexer for HT-SELEX data
SO METHODS
LA English
DT Article
DE Aptamers; HT-SELEX; Demultiplexing; Quality control
AB Aptamers, short and synthetic RNA/DNA molecules binding distinct targets with high affinity and specificity, are identified via Systematic Evolution of Ligands by Exponential Enrichment (SELEX), an in vitro procedure that, starting from a pool of random ssDNA/RNA sequences, selects sequences by amplifying target-affine species through a series of selection cycles. This versatile protocol has recently been combined with high throughput sequencing, allowing arbitrary stages of the selection to be sequenced and analyzed in silico. As a prerequisite, these data require extensive preprocessing by means of quality controls, error correction and demultiplexing, all while taking into account the specific design of aptamers. Existing solutions addressing this task are currently present only as integrated components in larger pipelines, limiting their applicability in independent software solutions.
Here we present AptaPLEX, a standalone and platform independent demultiplexer specifically designed for HT-SELEX data. Given the multiplexed data from one or multiple HT-SELEX experiments, AptaPLEX extracts and restores aptamers into the original selection cycles by identifying the barcode and primer regions in each read. AptaPLEX is capable of fuzzy matching for both the barcode and primers, and automatically corrects mismatches between forward and reverse reads for paired-end data. Our software provides a rich set of additional features and can easily be integrated into existing analysis automation pipelines on multiple platforms ranging from desktop machines to cloud based solutions. (C) 2016 Published by Elsevier Inc.
C1 [Hoinka, Jan; Przytycka, Teresa] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
RP Hoinka, J (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
EM jan.hoinka@nih.gov
FU Intramural Research Program of the NIH, National Library of Medicine
FX This work was supported by the Intramural Research Program of the NIH,
National Library of Medicine.
NR 18
TC 2
Z9 2
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 1046-2023
EI 1095-9130
J9 METHODS
JI Methods
PD AUG 15
PY 2016
VL 106
BP 82
EP 85
DI 10.1016/j.ymeth.2016.04.011
PG 4
WC Biochemical Research Methods; Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA DT9PZ
UT WOS:000381836100012
PM 27080809
ER
PT J
AU Billeskov, R
Tan, EV
Cang, M
Abalos, RM
Burgos, J
Pedersen, BV
Christensen, D
Agger, EM
Andersen, P
AF Billeskov, Rolf
Tan, Esterlina V.
Cang, Marjorie
Abalos, Rodolfo M.
Burgos, Jasmin
Pedersen, Bo Vestergaard
Christensen, Dennis
Agger, Else Marie
Andersen, Peter
TI Testing the H56 Vaccine Delivered in 4 Different Adjuvants as a
BCG-Booster in a Non-Human Primate Model of Tuberculosis
SO PLOS ONE
LA English
DT Article
ID BACILLUS-CALMETTE-GUERIN; T-CELL RESPONSES; MYCOBACTERIUM-TUBERCULOSIS;
PROTECTIVE IMMUNITY; CYNOMOLGUS MACAQUES; INTERFERON-GAMMA; RHESUS
MACAQUES; INFECTION; MEMORY; FREQUENCY
AB The search for new and improved tuberculosis (TB) vaccines has focused on IFN-gamma both for selecting antigens and for evaluating vaccine delivery strategies. The essential role of IFN-gamma in endogenous host protection is well established, but it is still uncertain whether this also holds true for vaccine protection. Here we evaluate the H56 fusion protein vaccine as a BCG booster in a non-human primate (NHP) model of TB that closely recapitulates human TB pathogenesis. To date, only a handful of novel adjuvants have been tested in the NHP model of TB, and therefore we administered H56 in 3 novel cationic liposome adjuvants of increasing immunogenicity (CAF01, CAF04, CAF05) and compared them to H56 in the IC31 (R) adjuvant previously reported to promote protection in this model. The individual clinical parameters monitored during infection (weight, ESR, X-ray) all correlated with survival, and boosting BCG with H56 in all adjuvants resulted in better survival rates compared to BCG alone. The adjuvants promoted IFN-gamma responses of increasing intensity as measured by ELISPOT in the peripheral blood, but the level of vaccine-specific IFN-gamma production did not correlate with or predict disease outcome. This study's main outcome underscores the importance of the choice of adjuvant for TB subunit vaccines, and secondly it highlights the need for better correlates of protection in preclinical models of TB.
C1 [Billeskov, Rolf; Christensen, Dennis; Agger, Else Marie; Andersen, Peter] Statens Serum Inst, Dept Infect Dis Immunol, Copenhagen, Denmark.
[Billeskov, Rolf] NCI, Vaccine Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Tan, Esterlina V.; Cang, Marjorie; Abalos, Rodolfo M.; Burgos, Jasmin] Leonard Wood Mem LWM Ctr Leprosy Res, Cebu, Philippines.
[Pedersen, Bo Vestergaard] Statens Serum Inst, Dept Epidemiol Res, Copenhagen, Denmark.
RP Billeskov, R; Andersen, P (reprint author), Statens Serum Inst, Dept Infect Dis Immunol, Copenhagen, Denmark.; Billeskov, R (reprint author), NCI, Vaccine Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM rob@ssi.dk; pa@ssi.dk
OI Christensen, Dennis/0000-0003-2382-8639; Billeskov,
Rolf/0000-0003-4533-7304
FU European Commission [FP7-HEALTH-2011.1.4-4-280873]; National Institutes
of Health [AI 105422]
FX The parts of this work that was performed at the SSI was funded by the
European Commission [contract number FP7-HEALTH-2011.1.4-4-280873
(ADITEC)], and National Institutes of Health [grant number AI 105422].
The funders had no role in design of studies or preparation of the
manuscript.
NR 43
TC 1
Z9 1
U1 5
U2 7
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 AUG 15
PY 2016
VL 11
IS 8
AR e0161217
DI 10.1371/journal.pone.0161217
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DT4SL
UT WOS:000381471100043
PM 27525651
ER
PT J
AU Desai, A
Krynitsky, J
Pohida, TJ
Zhao, HY
Schuck, P
AF Desai, Abhiksha
Krynitsky, Jonathan
Pohida, Thomas J.
Zhao, Huaying
Schuck, Peter
TI 3D-Printing for Analytical Ultracentrifugation
SO PLOS ONE
LA English
DT Article
ID VELOCITY ANALYTICAL ULTRACENTRIFUGATION; SEDIMENTATION EQUILIBRIUM;
PROTEIN INTERACTIONS; QUANTITATION; PRECISION; ACCURACY; DENSITY; SIZE
AB Analytical ultracentrifugation (AUC) is a classical technique of physical biochemistry providing information on size, shape, and interactions of macromolecules from the analysis of their migration in centrifugal fields while free in solution. A key mechanical element in AUC is the centerpiece, a component of the sample cell assembly that is mounted between the optical windows to allow imaging and to seal the sample solution column against high vacuum while exposed to gravitational forces in excess of 300,000 g. For sedimentation velocity it needs to be precisely sector-shaped to allow unimpeded radial macromolecular migration. During the history of AUC a great variety of centerpiece designs have been developed for different types of experiments. Here, we report that centerpieces can now be readily fabricated by 3D printing at low cost, from a variety of materials, and with customized designs. The new centerpieces can exhibit sufficient mechanical stability to withstand the gravitational forces at the highest rotor speeds and be sufficiently precise for sedimentation equilibrium and sedimentation velocity experiments. Sedimentation velocity experiments with bovine serum albumin as a reference molecule in 3D printed centerpieces with standard double-sector design result in sedimentation boundaries virtually indistinguishable from those in commercial double-sector epoxy centerpieces, with sedimentation coefficients well within the range of published values. The statistical error of the measurement is slightly above that obtained with commercial epoxy, but still below 1%. Facilitated by modern open-source design and fabrication paradigms, we believe 3D printed centerpieces and AUC accessories can spawn a variety of improvements in AUC experimental design, efficiency and resource allocation.
C1 [Desai, Abhiksha; Zhao, Huaying; Schuck, Peter] Natl Inst Biomed Imaging & Bioengn, Dynam Macromol Assembly Sect, Lab Cellular Imaging & Macromol Biophys, NIH, Bethesda, MD 20892 USA.
[Krynitsky, Jonathan; Pohida, Thomas J.] NIH, Div Computat Biosci, Ctr Informat Technol, Bethesda, MD 20892 USA.
RP Schuck, P (reprint author), Natl Inst Biomed Imaging & Bioengn, Dynam Macromol Assembly Sect, Lab Cellular Imaging & Macromol Biophys, NIH, Bethesda, MD 20892 USA.
EM schuckp@mail.nih.gov
FU Intramural Research Program of the National Institute of Biomedical
Imaging and Bioengineering, National Institutes of Health, United States
[ZIA EB000051-09 LCIM]
FX This work was supported by the Intramural Research Program of the
National Institute of Biomedical Imaging and Bioengineering, National
Institutes of Health, United States (ZIA EB000051-09 LCIM to PS). The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 61
TC 0
Z9 0
U1 12
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 AUG 15
PY 2016
VL 11
IS 8
AR e0155201
DI 10.1371/journal.pone.0155201
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DT4SL
UT WOS:000381471100001
PM 27525659
ER
PT J
AU Ofori, E
Zhu, XY
Etukala, JR
Peprah, K
Jordan, KR
Adkins, AA
Bricker, BA
Kang, HJ
Huang, XP
Roth, BL
Ablordeppey, SY
AF Ofori, Edward
Zhu, Xue Y.
Etukala, Jagan R.
Peprah, Kwakye
Jordan, Kamanski R.
Adkins, Adia A.
Bricker, Barbara A.
Kang, Hye J.
Huang, Xi-Ping
Roth, Bryan L.
Ablordeppey, Seth Y.
TI Design and synthesis of dual 5-HT1A and 5-HT7 receptor ligands
SO BIOORGANIC & MEDICINAL CHEMISTRY
LA English
DT Article
DE Dual receptor ligands; Multi-receptor targeting; CNS ligands; Serotonin
receptors; 5-HT1A receptor and 5-HT7 receptor ligands
ID ATYPICAL ANTIPSYCHOTIC-DRUG; SEROTONIN RECEPTORS; ROBUST PHARMACOLOGY;
NEGATIVE SYMPTOMS; PARTIAL AGONIST; DOPAMINE D-3; ARIPIPRAZOLE;
CARIPRAZINE; SCHIZOPHRENIA; ANTAGONIST
AB 5-HT1A and 5-HT7 receptors have been at the center of discussions recently due in part to their major role in the etiology of major central nervous system diseases such as depression, sleep disorders, and schizophrenia. As part of our search to identify dual targeting ligands for these receptors, we have carried out a systematic modification of a selective 5HT(7) receptor ligand culminating in the identification of several dual 5-HT1A and 5-HT7 receptor ligands. Compound 16, a butyrophenone derivative of tetrahydroisoquinoline (THIQ), was identified as the most potent agent with low nanomolar binding affinities to both receptors. Interestingly, compound 16 also displayed moderate affinity to other clinically relevant dopamine receptors. Thus, it is anticipated that compound 16 may serve as a lead for further exploitation in our quest to identify new ligands with the potential to treat diseases of CNS origin. Published by Elsevier Ltd.
C1 [Ofori, Edward; Zhu, Xue Y.; Etukala, Jagan R.; Peprah, Kwakye; Jordan, Kamanski R.; Adkins, Adia A.; Bricker, Barbara A.; Ablordeppey, Seth Y.] Florida A&M Univ, Coll Pharm & Pharmaceut Sci, Div Basic Pharmaceut Sci, Tallahassee, FL 32307 USA.
[Kang, Hye J.; Huang, Xi-Ping; Roth, Bryan L.] Univ North Carolina Chapel Hill, Sch Med, Dept Pharmacol, Chapel Hill, NC 27599 USA.
[Kang, Hye J.; Huang, Xi-Ping; Roth, Bryan L.] Univ North Carolina Chapel Hill, Sch Med, NIMH PDSP, Chapel Hill, NC 27599 USA.
[Roth, Bryan L.] Univ North Carolina Chapel Hill, Eshelman Sch Pharm, Div Chem Biol & Med Chem, Chapel Hill, NC 27599 USA.
RP Ablordeppey, SY (reprint author), Florida A&M Univ, Coll Pharm & Pharmaceut Sci, Div Basic Pharmaceut Sci, Tallahassee, FL 32307 USA.
FU NIH/NIGMS SCORE grant [2SC1GM116724]; RCMI grant from NIMHD [G12 RR
03020]; Pharmaceutical Research Center NIH/NCRR [1C06-RR12512-01];
National Institute of Mental Health's Psychoactive Drug Screening
Program [HHSN-271-2013-00017-C]; Title III Grant
FX This work would not have been possible without the continuing financial
support of the NIH/NIGMS SCORE grant number 2SC1GM116724, RCMI grant
number G12 RR 03020 from NIMHD and a Title III Grant to Florida A&M
University. The work was also supported in part by the Pharmaceutical
Research Center NIH/NCRR 1C06-RR12512-01 Grant. Ki
determinations and receptor binding profiles were generously provided by
the National Institute of Mental Health's Psychoactive Drug Screening
Program, Contract # HHSN-271-2013-00017-C (NIMH PDSP). The NIMH PDSP is
directed by Bryan L. Roth MD, PhD at the University of North Carolina at
Chapel Hill and Project Officer Jamie Driscoll at NIMH, Bethesda MD,
USA. Funding sources acknowledged had no involvement in the study
design, data collection and interpretation, or article preparation and
submission of this manuscript.
NR 42
TC 1
Z9 1
U1 5
U2 6
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0968-0896
EI 1464-3391
J9 BIOORGAN MED CHEM
JI Bioorg. Med. Chem.
PD AUG 15
PY 2016
VL 24
IS 16
BP 3464
EP 3471
DI 10.1016/j.bmc.2016.05.053
PG 8
WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry,
Organic
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry
GA DS2AF
UT WOS:000380515700015
PM 27312422
ER
PT J
AU Etukala, JR
Zhu, XY
Eyunni, SVK
Onyameh, EK
Ofori, E
Bricker, BA
Kang, HJ
Huang, P
Roth, BL
Ablordeppey, SY
AF Etukala, Jagan R.
Zhu, Xue Y.
Eyunni, Suresh V. K.
Onyameh, Edem K.
Ofori, Edward
Bricker, Barbara A.
Kang, Hye J.
Huang, Ping
Roth, Bryan L.
Ablordeppey, Seth Y.
TI Development of CNS multi-receptor ligands: Modification of known D-2
pharmacophores
SO BIOORGANIC & MEDICINAL CHEMISTRY
LA English
DT Article
DE Multi-receptor targeting; Dopamine receptor ligands; Antipsychotic;
Pharmacophore; CNS receptor
ID REVERSES MK-801-INDUCED IMPAIRMENT; INDUCED DOPAMINE RELEASE; SIGMA(2)
BINDING-SITE; ANTIPSYCHOTIC AGENT; PREFRONTAL CORTEX; BIPOLAR
DEPRESSION; WEIGHT-GAIN; HALOPERIDOL; DRUG; LURASIDONE
AB Several known D-2 pharmacophores have been explored as templates for identifying ligands with multiple binding affinities at dopamine and serotonin receptors considered as clinically relevant receptors in the treatment of neuropsychiatric diseases. This approach has resulted in the identification of ligands that target multiple CNS receptors while avoiding others associated with deleterious effects. In particular, compounds 11, 15 and 22 may have potential for further development as antipsychotic agents as they favorably interact with the clinically relevant receptors including D2R, 5-HT1AR, and 5-HT7R. We have also identified the pair of compounds 11 and 10 as high affinity D2R ligands with and without SERT binding affinities, respectively. These differential binding profiles endow the pair with the potential for evaluating SERT contributions to antipsychotic drug activity in animal behavioral models. In addition, compound 11 has no significant affinity for 5-HT2CR and binds only moderately to the H1R, suggesting it may not induce weight gain or sedation when used clinically. Taken together, compound 11 displays an interesting pharmacological profile that necessitates the evaluation of its functional and in vivo effects in animal models which are currently ongoing. Published by Elsevier Ltd.
C1 [Etukala, Jagan R.; Zhu, Xue Y.; Eyunni, Suresh V. K.; Onyameh, Edem K.; Ofori, Edward; Bricker, Barbara A.; Ablordeppey, Seth Y.] Florida A&M Univ, Coll Pharm & Pharmaceut Sci, Div Basic Pharmaceut Sci, Tallahassee, FL 32307 USA.
[Kang, Hye J.; Huang, Ping; Roth, Bryan L.] Univ North Carolina Chapel Hill, Sch Med, Dept Pharmacol, Chapel Hill, NC 27599 USA.
[Kang, Hye J.; Huang, Ping; Roth, Bryan L.] Univ North Carolina Chapel Hill, Sch Med, NIMH PDSP, Chapel Hill, NC 27599 USA.
[Roth, Bryan L.] Univ North Carolina Chapel Hill, Eshelman Sch Pharm, Div Chem Biol & Med Chem, Chapel Hill, NC 27599 USA.
RP Ablordeppey, SY (reprint author), Florida A&M Univ, Coll Pharm & Pharmaceut Sci, Div Basic Pharmaceut Sci, Tallahassee, FL 32307 USA.
EM seth.ablordeppey@famu.edu
FU NIH/NIGMS SCORE grant [2SC1GM116724]; NIMHD RCMI grant [G12 RR03020];
Title III Grant; Pharmaceutical Research Center NIH/NCRR [1C06RR12512];
National Institute of Mental Health's Psychoactive Drug Screening
Program [HHSN-271-2013-00017-C]
FX This work would not have been possible without the continuing financial
support of the NIH/NIGMS SCORE grant number 2SC1GM116724, NIMHD RCMI
grant number G12 RR03020 and a Title III Grant to Florida A&M
University. The work was also supported in part by the Pharmaceutical
Research Center NIH/NCRR grant number 1C06RR12512. Ki
determinations and receptor binding profiles were generously provided by
the National Institute of Mental Health's Psychoactive Drug Screening
Program, Contract #HHSN-271-2013-00017-C (NIMH PDSP). The NIMH PDSP is
directed by Bryan L. Roth MD, PhD at the University of North Carolina at
Chapel Hill and Project Officer Jamie Driscoll at NIMH, Bethesda MD,
USA. Funding sources acknowledged had no involvement in the study
design, data collection and interpretation, or article preparation and
submission of this manuscript.
NR 49
TC 0
Z9 0
U1 6
U2 6
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0968-0896
EI 1464-3391
J9 BIOORGAN MED CHEM
JI Bioorg. Med. Chem.
PD AUG 15
PY 2016
VL 24
IS 16
BP 3671
EP 3679
DI 10.1016/j.bmc.2016.06.011
PG 9
WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry,
Organic
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry
GA DS2AF
UT WOS:000380515700038
PM 27364609
ER
PT J
AU Kosa, P
Ghazali, D
Tanigawa, M
Barbour, C
Cortese, I
Kelley, W
Snyder, B
Ohayon, J
Fenton, K
Lehky, T
Wu, TX
Greenwood, M
Nair, G
Bielekova, B
AF Kosa, Peter
Ghazali, Danish
Tanigawa, Makoto
Barbour, Chris
Cortese, Irene
Kelley, William
Snyder, Blake
Ohayon, Joan
Fenton, Kaylan
Lehky, Tanya
Wu, Tianxia
Greenwood, Mark
Nair, Govind
Bielekova, Bibiana
TI Development of a sensitive Outcome for economical Drug screening for
Progressive Multiple sclerosis Treatment
SO FRONTIERS IN NEUROLOGY
LA English
DT Article
DE multiple sclerosis; clinical trial; outcome measure; composite scale;
progressive MS; disability scale; quantitative MRI
ID MAGNETIZATION-TRANSFER RATIO; CLINICAL-TRIALS; DIFFUSION MRI;
DOUBLE-BLIND; MATTER; BRAIN; NEUROPROTECTION; DISABILITY; ROBUST; MSFC
AB Therapeutic advance in progressive multiple sclerosis (MS) has been very slow. Based on the transformative role magnetic resonance imaging (MRI) contrast-enhancing lesions had on drug development for relapsing-remitting MS, we consider the lack of sensitive outcomes to be the greatest barrier for developing new treatments for progressive MS. The purpose of this study was to compare 58 prospectively acquired candidate outcomes in the real-world situation of progressive MS trials to select and validate the best-performing outcome. The 1-year pre-treatment period of adaptively designed IPPoMS (ClinicalTrials. gov #NCT00950248) and RIVITaLISe (ClinicalTrials. gov #NCT01212094) Phase II trials served to determine the primary outcome for the subsequent blinded treatment phase by comparing 8 clinical, 1 electrophysiological, 1 optical coherence tomography, 7 MRI volumetric, 9 quantitative T1 MRI, and 32 diffusion tensor imaging MRI outcomes. Fifteen outcomes demonstrated significant progression over 1 year (Delta) in the predetermined analysis and seven out of these were validated in two independent cohorts. Validated MRI outcomes had limited correlations with clinical scales, relatively poor signal-to-noise ratios (SNR) and recorded overlapping values between healthy subjects and MS patients with moderate-severe disability. Clinical measures correlated better, even though each reflects a somewhat different disability domain. Therefore, using machine-learning techniques, we developed a combinatorial weight-adjusted disability score (CombiWISE) that integrates four clinical scales: expanded disability status scale (EDSS), Scripps neurological rating scale, 25 foot walk and 9 hole peg test. CombiWISE outperformed all clinical scales (Delta = 9.10%; p = 0.0003) and all MRI outcomes. CombiWISE recorded no overlapping values between healthy subjects and disabled MS patients, had high SNR, and predicted changes in EDSS in a longitudinal assessment of 98 progressive MS patients and in a cross-sectional cohort of 303 untreated subjects. One point change in EDSS corresponds on average to 7.50 point change in CombiWISE with a standard error of 0.10. The novel validated clinical outcome, CombiWISE, outperforms the current broadly utilized MRI brain atrophy outcome and more than doubles sensitivity in detecting clinical deterioration in progressive MS in comparison to the scale traditionally used for regulatory approval, EDSS.
C1 [Kosa, Peter; Ghazali, Danish; Tanigawa, Makoto; Barbour, Chris; Kelley, William; Snyder, Blake; Bielekova, Bibiana] NINDS, Neuroimmunol Dis Unit, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
[Barbour, Chris; Greenwood, Mark] Montana State Univ, Dept Math Sci, Bozeman, MT 59717 USA.
[Cortese, Irene; Ohayon, Joan; Fenton, Kaylan; Nair, Govind] NINDS, Neuroimmunol Clin, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
[Lehky, Tanya] NINDS, EMG Sect, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
[Wu, Tianxia] NINDS, Clin Trials Unit, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
RP Bielekova, B (reprint author), NINDS, Neuroimmunol Dis Unit, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
EM bibi.bielekova@nih.gov
FU Intramural Research Program of National Institute of Neurological
Disorders and Stroke, National Institutes of Health [NS003055-08,
NS003056-08]
FX Intramural Research Program of National Institute of Neurological
Disorders and Stroke, National Institutes of Health (NS003055-08,
NS003056-08).
NR 40
TC 2
Z9 2
U1 6
U2 6
PU FRONTIERS MEDIA SA
PI LAUSANNE
PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015,
SWITZERLAND
SN 1664-2295
J9 FRONT NEUROL
JI Front. Neurol.
PD AUG 15
PY 2016
VL 7
AR 131
DI 10.3389/fneur.2016.00131
PG 14
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA DT3HD
UT WOS:000381370700001
PM 27574516
ER
PT J
AU Bai, RL
Hamel, E
AF Bai, Ruoli
Hamel, Ernest
TI (-)-Rhazinilam and the diphenylpyridazinone NSC 613241: Two compounds
inducing the formation of morphologically similar tubulin spirals but
binding apparently to two distinct sites on tubulin
SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
LA English
DT Article
DE Diphenylpyridazinone derivatives; NSC 613241; (-)-Rhazinilam; Tubulin
polymer of aberrant morphology; Inhibition of tubulin assembly;
Glutaraldehyde-fixed microtubules
ID MICROTUBULE-ASSOCIATED PROTEINS; AMINO-ACID-SEQUENCE; ANTIMITOTIC
AGENTS; STRUCTURAL BASIS; PORCINE BRAIN; BETA-TUBULIN; TAXOID SITE;
VINBLASTINE; LAULIMALIDE; RHAZINILAM
AB The most potent microtubule assembly inhibitor of newer diphenylpyridazinone derivatives examined was NSC 613241. Because NSC 613241 and (-)-rhazinilam also induce the formation of similar 2-filament spirals, these aberrant reactions were compared. Spiral formation with both compounds was enhanced by GTP and inhibited by GDP and by 15 other inhibitors of microtubule assembly. Similarly, microtubule assembly induced by paclitaxel or laulimalide is enhanced by GTP and inhibited by GDP and assembly inhibitors, but neither [H-3]NSC 613241 nor [H-3](-)-rhazinilam bound to microtubules or inhibited the binding of [H-3]paclitaxel or [H-3]peloruside A to microtubules. Differences in the pitch of aberrant polymers were found: NSC 613241-induced and (-)-rhazinilam-induced spirals had average repeats of 85 and 79-80 nm, respectively. We found no binding of [H-3]NSC 613241 or [H-3](-)-rhazinilam to alpha beta-tubulin dimer, but both compounds were incorporated into the polymers they induced in substoichiometric reactions, with as little as 0.1-0.2 mol compound/mal of tubulin, and no cross-inhibition by NSC 613241 or (-)-rhazinilam into spirals occurred. Under reaction conditions where neither compound induced spiral formation, both compounds together synergistically induced substantial spiral formation. We conclude that (-)-rhazinilam and NSC 613241 bind to different sites on tubulin that differ from binding sites for other antitubulin agents. Published by Elsevier Inc.
C1 [Bai, Ruoli; Hamel, Ernest] NCI, Screening Technol Branch, Dev Therapeut Program,NIH, Div Canc Treatment & Diag,Frederick Natl Lab Canc, Frederick, MD 21702 USA.
RP Hamel, E (reprint author), Frederick Natl Lab Canc Res, Bldg 322,Room 102, Frederick, MD 21702 USA.
EM hamele@mail.nih.gov
FU Intramural NIH HHS [Z99 CA999999]
NR 43
TC 1
Z9 1
U1 2
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0003-9861
EI 1096-0384
J9 ARCH BIOCHEM BIOPHYS
JI Arch. Biochem. Biophys.
PD AUG 15
PY 2016
VL 604
BP 63
EP 73
DI 10.1016/j.abb.2016.06.008
PG 11
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA DS2PY
UT WOS:000380627200008
PM 27311615
ER
PT J
AU Li, SS
Sun, YF
Huang, CY
Follmann, DA
Krause, R
AF Li, Shanshan
Sun, Yifei
Huang, Chiung-Yu
Follmann, Dean A.
Krause, Richard
TI Recurrent event data analysis with intermittently observed time-varying
covariates
SO STATISTICS IN MEDICINE
LA English
DT Article
DE estimating equations; kernel smoothing; partial likelihood; recurrent
events; survival analysis
ID SEMIPARAMETRIC ANALYSIS; SURVIVAL ANALYSIS; REGRESSION-MODEL; CASE
SERIES
AB Although recurrent event data analysis is a rapidly evolving area of research, rigorous studies on estimation of the effects of intermittently observed time-varying covariates on the risk of recurrent events have been lacking. Existing methods for analyzing recurrent event data usually require that the covariate processes are observed throughout the entire follow-up period. However, covariates are often observed periodically rather than continuously. We propose a novel semiparametric estimator for the regression parameters in the popular proportional rate model. The proposed estimator is based on an estimated score function where we kernel smooth the mean covariate process. We show that the proposed semiparametric estimator is asymptotically unbiased, normally distributed, and derives the asymptotic variance. Simulation studies are conducted to compare the performance of the proposed estimator and the simple methods carrying forward the last covariates. The different methods are applied to an observational study designed to assess the effect of group A streptococcus on pharyngitis among school children in India. Copyright (c) 2016 John Wiley & Sons, Ltd.
C1 [Li, Shanshan] Indiana Univ Fairbanks, Sch Publ Hlth, Dept Biostat, Indianapolis, IN 46202 USA.
[Sun, Yifei; Huang, Chiung-Yu] Johns Hopkins Univ, Dept Biostat, Baltimore, MD 21205 USA.
[Huang, Chiung-Yu] Johns Hopkins Univ, Div Biostat & Bioinformat, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21205 USA.
[Follmann, Dean A.; Krause, Richard] NIAID, Natl Inst Hlth, Bethesda, MD 20817 USA.
RP Huang, CY (reprint author), Johns Hopkins Univ, Div Biostat & Bioinformat, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21205 USA.
EM cyhuang@jhu.edu
FU National Cancer Institute [R01CA193888]
FX The authors are grateful to the editor, associate editor, and referees
for their comments that helped improve this paper. This research was
supported by the National Cancer Institute grant R01CA193888.
NR 30
TC 0
Z9 0
U1 2
U2 3
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 AUG 15
PY 2016
VL 35
IS 18
BP 3049
EP 3065
DI 10.1002/sim.6901
PG 17
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 DR6PZ
UT WOS:000380025100002
PM 26887664
ER
PT J
AU Begre, L
Rohner, E
Mbulaiteye, SM
Egger, M
Bohlius, J
AF Begre, Lorin
Rohner, Eliane
Mbulaiteye, Sam M.
Egger, Matthias
Bohlius, Julia
TI Is human herpesvirus 8 infection more common in men than in women?
Systematic review and meta-analysis
SO INTERNATIONAL JOURNAL OF CANCER
LA English
DT Review
DE human herpesvirus 8; Kaposi sarcoma; seroprevalence; gender;
meta-analysis
ID SARCOMA-ASSOCIATED HERPESVIRUS; SEXUALLY-TRANSMITTED-DISEASES;
MOTHER-TO-CHILD; KAPOSIS-SARCOMA; RISK-FACTORS; GENERAL-POPULATION;
ENDEMIC POPULATION; UNITED-STATES; TRANSMISSION; SEROPREVALENCE
AB All forms of Kaposi sarcoma (KS) are more common in men than in women. It is unknown if this is due to a higher prevalence of human herpesvirus 8 (HHV-8), the underlying cause of KS, in men compared to women. We did a systematic review and meta-analysis to examine the association between HHV-8 seropositivity and gender in the general population. Studies in selected populations like for example, blood donors, hospital patients and men who have sex with men were excluded. We searched Medline and Embase from January 1994 to February 2015. We included observational studies that recruited participants from the general population and reported HHV-8 seroprevalence for men and women or boys and girls. We used random-effects meta-analysis to pool odds ratios (OR) of the association between HHV-8 and gender. We used meta-regression to identify effect modifiers, including age, geographical region and type of HHV-8 antibody test. We included 22 studies, with 36,175 participants. Men from sub-Saharan Africa (SSA) [OR 1.21, 95% confidence interval (CI) 1.09-1.34], but not men from elsewhere (OR 0.94, 95% CI 0.83-1.06), were more likely to be HHV-8 seropositive than women (p value for interaction = 0.010). There was no difference in HHV-8 seroprevalence between boys and girls from SSA (OR 0.90, 95% CI 0.72-1.13). The type of HHV-8 assay did not affect the overall results. A higher HHV-8 seroprevalence in men than women in SSA may partially explain why men have a higher KS risk in this region.
C1 [Begre, Lorin; Rohner, Eliane; Egger, Matthias; Bohlius, Julia] Univ Bern, ISPM, Finkenhubelweg 11, CH-3012 Bern, Switzerland.
[Mbulaiteye, Sam M.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Egger, Matthias] Univ Cape Town, Sch Publ Hlth & Family Med, Ctr Infect Dis Epidemiol & Res, ZA-7925 Cape Town, South Africa.
RP Bohlius, J (reprint author), Univ Bern, ISPM, Finkenhubelweg 11, CH-3012 Bern, Switzerland.
EM julia.bohlius@ispm.unibe.ch
OI Rohner, Eliane/0000-0002-0554-2875
FU National Institute of Allergy and Infectious Diseases of the National
Institutes of Health [U01AI069924]; National Cancer Institute
[5U01A1069924-05]; Swiss National Science Foundation [Ambizione-PROSPER
PZ00P3_160407]
FX Grant sponsor: National Institute of Allergy and Infectious Diseases of
the National Institutes of Health; Grant number: U01AI069924 to M.E.;
Grant sponsor: National Cancer Institute; Grant number: 5U01A1069924-05
to M.E.; Grant sponsor: Swiss National Science Foundation; Grant number:
Ambizione-PROSPER PZ00P3_160407 to J.B.
NR 41
TC 1
Z9 1
U1 0
U2 2
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 AUG 15
PY 2016
VL 139
IS 4
BP 776
EP 783
DI 10.1002/ijc.30129
PG 8
WC Oncology
SC Oncology
GA DP3TM
UT WOS:000378418300013
PM 27062038
ER
PT J
AU Hare, DJ
Raven, EP
Roberts, BR
Bogeski, M
Portbury, SD
McLean, CA
Masters, CL
Connor, JR
Bush, AI
Crouch, PJ
Doble, PA
AF Hare, Dominic J.
Raven, Erika P.
Roberts, Blaine R.
Bogeski, Mirjana
Portbury, Stuart D.
McLean, Catriona A.
Masters, Colin L.
Connor, James R.
Bush, Ashley I.
Crouch, Peter J.
Doble, Philip A.
TI Laser ablation-inductively coupled plasma-mass spectrometry imaging of
white and gray matter iron distribution in Alzheimer's disease frontal
cortex
SO NEUROIMAGE
LA English
DT Article
ID NON-HAEMIN IRON; LA-ICP-MS; BRAIN IRON; IN-VIVO; SUBSTANTIA-NIGRA; MRI
CONTRAST; PARKINSONS-DISEASE; TRANSITION-METALS; CEREBRAL-CORTEX; TISSUE
AB Iron deposition in the brain is a feature of normal aging, though in several neurodegenerative disorders, including Alzheimer's disease, the rate of iron accumulation is more advanced than in age-matched controls. Using laser ablation-inductively coupled plasma-mass spectrometry imaging we present here a pilot study that quantitatively assessed the iron content of white and gray matter in paraffin-embedded sections from the frontal cortex of Alzheimer's and control subjects. Using the phosphorus image as a confirmed proxy for the white/gray matter boundary, we found that increased intrusion of iron into gray matter occurs in the Alzheimer's brain compared to controls, which may be indicative of either a loss of iron homeostasis in this vulnerable brain region, or provide evidence of increased inflammatory processes as a response to chronic neurodegeneration. We also observed a trend of increasing iron within the white matter of the frontal cortex, potentially indicative of disrupted iron metabolism preceding loss of myelin integrity. Considering the known potential toxicity of excessive iron in the brain, our results provide supporting evidence for the continuous development of novel magnetic resonance imaging approaches for assessing white and gray matter iron accumulation in Alzheimer's disease. Crown Copyright (C) 2016 Published by Elsevier Inc. All rights reserved.
C1 [Hare, Dominic J.; Doble, Philip A.] Univ Technol Sydney, Elemental Bioimaging Facil, Sydney, NSW 2007, Australia.
[Hare, Dominic J.; Roberts, Blaine R.; Bogeski, Mirjana; Portbury, Stuart D.; Masters, Colin L.; Bush, Ashley I.] Univ Melbourne, Florey Inst Neurosci & Mental Hlth, Melbourne, Vic 3010, Australia.
[Raven, Erika P.] Georgetown Univ, Ctr Funct & Mol Imaging, Med Ctr, Washington, DC 20057 USA.
[Raven, Erika P.] NINDS, Adv Magnet Resonance Imaging Sect, Lab Funct & Mol Imaging, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
[McLean, Catriona A.] Alfred Hosp, Dept Anat Pathol, Melbourne, Vic, Australia.
[McLean, Catriona A.] Monash Univ, Dept Med, Cent Clin Sch, Clayton, Vic 3800, Australia.
[Connor, James R.] Penn State Hershey Med Ctr, Dept Neural & Behav Sci, Hershey, PA USA.
[Connor, James R.] Penn State Hershey Med Ctr, Dept Neurosurg, Hershey, PA USA.
[Crouch, Peter J.] Univ Melbourne, Dept Pathol, Sch Biomed Sci, Melbourne, Vic 3010, Australia.
RP Hare, DJ; Doble, PA (reprint author), Univ Technol Sydney, POB 123, Sydney, NSW 2007, Australia.
EM dominic.hare@uts.edu.au; philip.doble@uts.edu.au
FU Australian Research Council Linkage Project [LP120200081, LP140100095];
ESI Ltd.; Agilent Technologies; National Science Foundation Graduate
Research Fellowship [DGE-1444316]; National Health and Medical Research
Council [1005651, 1061550]; Victorian Government's Operational
Infrastructure Support Program; Victorian Brain Bank Network
FX The authors would like to thank Dr. Ian Birchall and Dr. Jeff Duyn for
their helpful advice, and Ms. Fairlie Hilton of the Victorian Brain Bank
Network for her assistance with case notes. D.J.H. and P.A.D. are
supported by funds from Australian Research Council Linkage Project
(LP120200081) in conjunction with ESI Ltd. and Agilent Technologies.
D.J.H. and B.R.R. are additionally supported through Australian Research
Council Linkage Project (LP140100095) with Agilent Technologies. E.P.R.
is supported by the National Science Foundation Graduate Research
Fellowship under Grant No. DGE-1444316. P.J.C. is supported by funds
from the National Health and Medical Research Council (1005651 and
1061550). We gratefully acknowledge the support of the Victorian
Government's Operational Infrastructure Support Program and the
Victorian Brain Bank Network.
NR 74
TC 1
Z9 1
U1 20
U2 46
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 AUG 15
PY 2016
VL 137
BP 124
EP 131
DI 10.1016/j.neuroimage.2016.05.057
PG 8
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA DO8QO
UT WOS:000378048700013
PM 27233149
ER
PT J
AU Zavala, B
Tan, HL
Ashkan, K
Foltynie, T
Limousin, P
Zrinzo, L
Zaghloul, K
Brown, P
AF Zavala, Baltazar
Tan, Huiling
Ashkan, Keyoumars
Foltynie, Thomas
Limousin, Patricia
Zrinzo, Ludvic
Zaghloul, Kareem
Brown, Peter
TI Human subthalamic nucleus-medial frontal cortex theta phase coherence is
involved in conflict and error related cortical monitoring
SO NEUROIMAGE
LA English
DT Article
DE Conflict; Subthalamic nucleus; Theta; Coherence; Errors
ID ANTERIOR CINGULATE CORTEX; DEEP BRAIN-STIMULATION; PARKINSONS-DISEASE;
COGNITIVE CONTROL; DECISION-MAKING; RESPONSE CONFLICT; TASK-DIFFICULTY;
DYNAMICS; OSCILLATIONS; RESOLUTION
AB The medial prefrontal cortex (mPFC) is thought to control the shift from automatic to controlled action selection when conflict is present or when mistakes have been recently committed. Growing evidence suggests that this process involves frequency specific communication in the theta (4-8 Hz) band between the mPFC and the subthalamic nucleus (STN), which is the main target of deep brain stimulation (DBS) for Parkinson's disease. Key in this hypothesis is the finding that DBS can lead to impulsivity by disrupting the correlation between higher mPFC oscillations and slower reaction times during conflict. In order to test whether theta band coherence between the mPFC and the STN underlies adjustments to conflict and to errors, we simultaneously recorded mPFC and STN electrophysiological activity while DBS patients performed an arrowed flanker task. These recordings revealed higher theta phase coherence between the two sites during the high conflict trials relative to the low conflict trials. These differences were observed soon after conflicting arrows were displayed, but before a response was executed. Furthermore, trials that occurred after an error was committed showed higher phase coherence relative to trials that followed a correct trial, suggesting that mPFC-STN connectivity may also play a role in error related adjustments in behavior. Interestingly, the phase coherence we observed occurred before increases in theta power, implying that the theta phase and power may influence behavior at separate times during cortical monitoring. Finally, we showed that pre-stimulus differences in STN theta power were related to the reaction time on a given trial, which may help adjust behavior based on the probability of observing conflict during a task. (C) 2016 The Authors. Published by Elsevier Inc.
C1 [Zavala, Baltazar; Tan, Huiling; Brown, Peter] Univ Oxford, John Radcliffe Hosp, Nuffield Dept Clin Neurol, Oxford OX3 9DU, England.
[Zavala, Baltazar; Zaghloul, Kareem] NIH, Surg Neurol Branch, 10 Ctr Dr,3D20, Bethesda, MD 20814 USA.
[Tan, Huiling; Brown, Peter] Univ Oxford, Med Res Council, Brain Network Dynam Unit, Mansfield Rd, Oxford OX1 3TH, England.
[Ashkan, Keyoumars] Kings Coll Hosp London, Dept Neurosurg, Kings Coll, London SE5 9RS, England.
[Foltynie, Thomas; Limousin, Patricia; Zrinzo, Ludvic] UCL Inst Neurol, Sobell Dept Motor Neurosci & Movement Disorders, London WC1 3BG, England.
RP Zavala, B (reprint author), Natl Inst Neurol Dis & Stroke, Surg Neurol Branch, Bldg 10,Room 3D20,10 Ctr Dr, Bethesda, MD 20892 USA.
EM zarzavala@gmail.com
OI Zavala, Baltazar/0000-0002-7284-7994; Brown, Peter/0000-0002-5201-3044;
Tan, Huiling /0000-0001-8038-3029
FU National Institutes of Health Oxford-Cambridge fellowship; Department of
Health National Institute for Health Research UCL Biomedical Research
Center; Monument Trust; Parkinson's Appeal for Deep Brain Stimulation;
Medical Research Council; Department of Health National Institute for
Health Research Oxford Biomedical Research Centre
FX B.Z. is supported by the National Institutes of Health Oxford-Cambridge
fellowship. T.F. and L.Z. are funded by the Department of Health
National Institute for Health Research UCL Biomedical Research Center,
The Monument Trust, and Parkinson's Appeal for Deep Brain Stimulation.
P.B. and H.T. are funded by the Medical Research Council, and P.B. is
further funded by the Department of Health National Institute for Health
Research Oxford Biomedical Research Centre.
NR 50
TC 2
Z9 2
U1 10
U2 15
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 AUG 15
PY 2016
VL 137
BP 178
EP 187
DI 10.1016/j.neuroimage.2016.05.031
PG 10
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA DO8QO
UT WOS:000378048700018
PM 27181763
ER
PT J
AU Scuteri, A
Morrell, CH
Orru, M
AlGhatrif, M
Saba, PS
Terracciano, A
Ferreli, LAP
Loi, F
Marongiu, M
Pilia, MG
Delitala, A
Tarasov, KV
Schlessinger, D
Ganau, A
Cucca, F
Lakatta, EG
AF Scuteri, Angelo
Morrell, Christopher H.
Orru, Marco
AlGhatrif, Majid
Saba, Pier Sergio
Terracciano, Antonio
Ferreli, Liana Anna Pina
Loi, Francesco
Marongiu, Michele
Pilia, Maria Grazia
Delitala, Alessandro
Tarasov, Kirill V.
Schlessinger, David
Ganau, Antonello
Cucca, Francesco
Lakatta, Edward G.
TI Gender specific profiles of white coat and masked hypertension impacts
on arterial structure and function in the SardiNIA study
SO INTERNATIONAL JOURNAL OF CARDIOLOGY
LA English
DT Article
DE Arterial stiffness; Pulse wave velocity; Carotid thickness; Arterial
aging; Masked hypertension; White coat hypertension; 24 hour blood
pressure monitoring
ID PULSE-WAVE VELOCITY; AMBULATORY BLOOD-PRESSURE; LONG-TERM RISK;
SUSTAINED HYPERTENSION; COGNITIVE IMPAIRMENT; METABOLIC SYNDROME; ORGAN
DAMAGE; METAANALYSIS; STIFFNESS; STROKE
AB Background: There is no definite consensus on the CV burden associated to Masked hypertension (MH) or White Coat Hypertension (WCH) - conditions that can be detected by out-of-office blood pressure measurements (24 hour Ambulatory Blood Pressure Monitoring, 24 h ABPM).
Methods: We investigated the association of WCH and MH with arterial aging, indexed by a range of parameters of large artery structure and function in 2962 subjects, taking no antihypertensive medications, who are participating in a large community-based population of both men and women over a broad age range (14-102 years).
Results: The overall prevalence of WCH was 9.5% and was 5.0% for MH, with 54.9% of subjects classified as true normotensive and 30.6% as true hypertensive. Both WCH and MH were associated with a stiffer aorta, a less distensible and thicker common carotid artery, and greater central BP than true normotensive subjects. Notably, the profile of arterial alterations in WCH and MH did not significantly differ from what was observed in true hypertensive subjects. The arterial changes accompanying WCH and MH differed in men and women, with women showing a greater tendency towards concentric remodeling, greater parietal wall stress, and PWV than men.
Conclusion: Both WCH, and MH are associated with early arterial aging, and therefore, neither can be regarded as innocent conditions. Future studies are required to establish whether measurement of arterial aging parameters in subjects with WCH or MH will identify subjects at higher risk of CV events and cognitive impairment, who may require more clinical attention and pharmacological intervention. (C) 2016 Published by Elsevier Ireland Ltd.
C1 [Morrell, Christopher H.; AlGhatrif, Majid; Tarasov, Kirill V.; Schlessinger, David; Lakatta, Edward G.] NIA, NIH, Baltimore, MD 21224 USA.
[Orru, Marco; Ferreli, Liana Anna Pina; Loi, Francesco; Marongiu, Michele; Pilia, Maria Grazia; Delitala, Alessandro; Cucca, Francesco] Cittadella Univ Monserrato, Ist Ric Genet & Biomed, CNR, Cagliari, Italy.
[Saba, Pier Sergio; Ganau, Antonello] Univ Sassari, I-07100 Sassari, Italy.
[Terracciano, Antonio] Florida State Univ, Coll Med, Tallahassee, FL 32306 USA.
[Morrell, Christopher H.] Loyola Univ Maryland, Baltimore, MD USA.
[Orru, Marco] Presidio Osped A Businco, Unita Operat Complessa Cardiol, Cagliari, Italy.
RP Scuteri, A (reprint author), Policlin Tor Vergata, Hypertens Ctr, Hypertens & Nephrol Unit, Rome, Italy.
EM angeloelefante@interfree.it
RI Delitala, Alessandro/L-3194-2016
OI Delitala, Alessandro/0000-0003-1729-8969
FU NIA [NO1-AG-1-2109]; Intramural Research Program of the NIH, U.S.
National Institute on Aging
FX The SardiNIA team was supported by Contract NO1-AG-1-2109 from the NIA.
This research was supported in part by the Intramural Research Program
of the NIH, U.S. National Institute on Aging.
NR 31
TC 2
Z9 2
U1 1
U2 3
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 AUG 15
PY 2016
VL 217
BP 92
EP 98
DI 10.1016/j.ijcard.2016.04.172
PG 7
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA DO5OO
UT WOS:000377832700014
PM 27179214
ER
PT J
AU Metcalf, CJE
Farrar, J
Cutts, FT
Basta, NE
Graham, AL
Lessler, J
Ferguson, NM
Burke, DS
Grenfell, BT
AF Metcalf, C. Jessica E.
Farrar, Jeremy
Cutts, Felicity T.
Basta, Nicole E.
Graham, Andrea L.
Lessler, Justin
Ferguson, Neil M.
Burke, Donald S.
Grenfell, Bryan T.
TI Use of serological surveys to generate key insights into the changing
global landscape of infectious disease
SO LANCET
LA English
DT Editorial Material
ID INFLUENZA; TRANSMISSION; DYNAMICS; ANTIBODY; MODEL
C1 [Metcalf, C. Jessica E.; Graham, Andrea L.; Grenfell, Bryan T.] Princeton Univ, Dept Ecol & Evolutionary Biol, Princeton, NJ 08544 USA.
[Metcalf, C. Jessica E.; Basta, Nicole E.; Graham, Andrea L.; Grenfell, Bryan T.] NIH, Fogarty Int Ctr, Bldg 10, Bethesda, MD 20892 USA.
[Farrar, Jeremy] Wellcome Trust Res Labs, Gibbs Bldg, London, England.
[Cutts, Felicity T.] London Sch Hyg & Trop Med, London, England.
[Basta, Nicole E.] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA.
[Lessler, Justin] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
[Ferguson, Neil M.] Imperial Coll London, Dept Med, Sch Publ Hlth, London, England.
[Burke, Donald S.] Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA USA.
RP Metcalf, CJE (reprint author), Princeton Univ, Dept Ecol & Evolutionary Biol, Princeton, NJ 08544 USA.
EM cmetcalf@princeton.edu
RI Graham, Andrea/A-8808-2010;
OI Graham, Andrea/0000-0002-6580-2755; Lessler, Justin/0000-0002-9741-8109;
/0000-0002-5704-8094
FU Medical Research Council [, MR/K010174/1]; NICHD NIH HHS [P2C HD047879];
NIH HHS [DP5 OD009162]
NR 14
TC 7
Z9 7
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0140-6736
EI 1474-547X
J9 LANCET
JI Lancet
PD AUG 13
PY 2016
VL 388
IS 10045
BP 728
EP 730
DI 10.1016/S0140-6736(16)30164-7
PG 3
WC Medicine, General & Internal
SC General & Internal Medicine
GA DT1UX
UT WOS:000381268700033
PM 27059886
ER
PT J
AU Verma, A
Verma, SS
Pendergrass, SA
Crawford, DC
Crosslin, DR
Kuivaniemi, H
Bush, WS
Bradford, Y
Kullo, I
Bielinski, SJ
Li, RL
Denny, JC
Peissig, P
Hebbring, S
De Andrade, M
Ritchie, MD
Tromp, G
AF Verma, Anurag
Verma, Shefali S.
Pendergrass, Sarah A.
Crawford, Dana C.
Crosslin, David R.
Kuivaniemi, Helena
Bush, William S.
Bradford, Yuki
Kullo, Iftikhar
Bielinski, Suzette J.
Li, Rongling
Denny, Joshua C.
Peissig, Peggy
Hebbring, Scott
De Andrade, Mariza
Ritchie, Marylyn D.
Tromp, Gerard
TI eMERGE Phenome-Wide Association Study (PheWAS) identifies clinical
associations and pleiotropy for stop-gain variants
SO BMC MEDICAL GENOMICS
LA English
DT Article; Proceedings Paper
CT 5th Translational Bioinformatics Conference (TBC)
CY NOV 07-09, 2015
CL Tokyo, JAPAN
ID ELECTRONIC MEDICAL-RECORDS; GENETIC-VARIANTS; GENOME; SUSCEPTIBILITY;
POLYMORPHISMS; DISEASE; HYPOTHYROIDISM; ANNOTATION; CHALLENGES;
DISPERSION
AB Background: We explored premature stop-gain variants to test the hypothesis that variants, which are likely to have a consequence on protein structure and function, will reveal important insights with respect to the phenotypes associated with them. We performed a phenome-wide association study (PheWAS) exploring the association between a selected list of functional stop-gain genetic variants (variation resulting in truncated proteins or in nonsense-mediated decay) and an extensive group of diagnoses to identify novel associations and uncover potential pleiotropy.
Results: In this study, we selected 25 stop-gain variants: 5 stop-gain variants with previously reported phenotypic associations, and a set of 20 putative stop-gain variants identified using dbSNP. For the PheWAS, we used data from the electronic MEdical Records and GEnomics (eMERGE) Network across 9 sites with a total of 41,057 unrelated patients. We divided all these samples into two datasets by equal proportion of eMERGE site, sex, race, and genotyping platform. We calculated single effect associations between these 25 stop-gain variants and ICD-9 defined case-control diagnoses. We also performed stratified analyses for samples of European and African ancestry. Associations were adjusted for sex, site, genotyping platform and the first three principal components to account for global ancestry. We identified previously known associations, such as variants in LPL associated with hyperglyceridemia indicating that our approach was robust. We also found a total of three significant associations with p < 0.01 in both datasets, with the most significant replicating result being LPL SNP rs328 and ICD-9 code 272. 1 "Disorder of Lipoid metabolism" (p(discovery) = 2.59x10-6, p(replicating) = 2.7x10-4). The other two significant replicated associations identified by this study are: variant rs1137617 in KCNH2 gene associated with ICD-9 code category 244 "Acquired Hypothyroidism" (p(discovery) = 5.31x103, p(replicating) = 1.15x10-3) and variant rs12060879 in DPT gene associated with ICD-9 code category 996 "Complications peculiar to certain specified procedures" (p(discovery) = 8. 65x103, p(replicating) = 4.16x10-3).
Conclusion: In conclusion, this PheWAS revealed novel associations of stop-gained variants with interesting phenotypes (ICD-9 codes) along with pleiotropic effects.
C1 [Verma, Anurag; Verma, Shefali S.; Bradford, Yuki; Ritchie, Marylyn D.] Penn State Univ, Ctr Syst Genom, Dept Biochem & Mol Biol, University Pk, PA 16802 USA.
[Verma, Anurag; Verma, Shefali S.; Pendergrass, Sarah A.; Ritchie, Marylyn D.] Geisinger Hlth Syst, Biomed & Translat Informat, Danville, PA USA.
[Kuivaniemi, Helena; Tromp, Gerard] Univ Stellenbosch, Fac Med & Hlth Sci, Dept Biomed Sci, Div Mol Biol & Human Genet, ZA-7505 Tygerberg, South Africa.
[Crawford, Dana C.; Bush, William S.] Case Western Reserve Univ, Cleveland, OH 44106 USA.
[Crosslin, David R.] Univ Washington, Dept Med, Div Med Genet, Seattle, WA 98195 USA.
[Denny, Joshua C.] Vanderbilt Univ, 221 Kirkland Hall, Nashville, TN 37235 USA.
[Peissig, Peggy; Hebbring, Scott] Marshfield Clin Fdn Med Res & Educ, Marshfield, WI USA.
[De Andrade, Mariza] Mayo Clin, Rochester, MN USA.
[Li, Rongling] NHGRI, Bethesda, MD 20892 USA.
RP Verma, A; Verma, SS (reprint author), Penn State Univ, Ctr Syst Genom, Dept Biochem & Mol Biol, University Pk, PA 16802 USA.
EM anurag.verma@psu.edu; szs14@psu.edu
OI Kuivaniemi, Helena/0000-0001-5753-8766
FU NCATS NIH HHS [UL1 TR000427]; NHGRI NIH HHS [U01 HG006388, U01 HG004424,
U01 HG004438, U01 HG006375, U01 HG006378, U01 HG006379, U01 HG006380,
U01 HG006382, U01 HG006385, U01 HG006389, U01 HG006828, U01 HG006830,
U01 HG008657, U01 HG008684, U01 HG008701]
NR 52
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 1755-8794
J9 BMC MED GENOMICS
JI BMC Med. Genomics
PD AUG 12
PY 2016
VL 9
SU 1
AR 32
DI 10.1186/s12920-016-0191-8
PG 7
WC Genetics & Heredity
SC Genetics & Heredity
GA DT2OH
UT WOS:000381319300005
PM 27535653
ER
PT J
AU Goodman, PJ
Tangen, CM
Darke, AK
Arnold, KB
Hartline, J
Yee, M
Anderson, K
Caban-Holt, A
Christen, WG
Cassano, PA
Lance, P
Klein, EA
Crowley, JJ
Minasian, LM
Meyskens, FL
AF Goodman, Phyllis J.
Tangen, Catherine M.
Darke, Amy K.
Arnold, Kathryn B.
Hartline, JoAnn
Yee, Monica
Anderson, Karen
Caban-Holt, Allison
Christen, William G.
Cassano, Patricia A.
Lance, Peter
Klein, Eric A.
Crowley, John J.
Minasian, Lori M.
Meyskens, Frank L.
TI Opportunities and challenges in incorporating ancillary studies into a
cancer prevention randomized clinical trial
SO TRIALS
LA English
DT Article
DE Prostate cancer; Ancillary studies; Randomized controlled trial; Study
implementation
ID VITAMIN-E; ALZHEIMERS-DISEASE; PROSTATE-CANCER; SELENIUM; SELECT;
DEMENTIA; RISK
AB Background: The Selenium and Vitamin E Cancer Prevention Trial (SELECT) was a randomized, double-blind, placebo-controlled, prostate cancer prevention study funded by the National Cancer Institute and conducted by SWOG (Southwest Oncology Group). A total of 35,533 men were assigned randomly to one of four treatment groups (vitamin E + placebo, selenium + placebo, vitamin E + selenium, placebo + placebo). At the time of the trial's development, NIH had invested substantial resources in evaluating the potential benefits of these antioxidants. To capitalize on the knowledge gained from following a large cohort of healthy, aging males on the effects of selenium and/or vitamin E, ancillary studies with other disease endpoints were solicited.
Methods: Four ancillary studies were added. Each drew from the same population but had independent objectives and an endpoint other than prostate cancer. These studies fell into two categories: those prospectively enrolling and following participants (studies of Alzheimer's disease and respiratory function) and those requiring a retrospective medical record review after a reported event (cataracts/age-related macular degeneration and colorectal screening). An examination of the challenges and opportunities of adding ancillary studies is provided. The impact of the ancillary studies on adherence to SELECT was evaluated using a Cox proportional hazards model.
Results: While the addition of ancillary studies appears to have improved participant adherence to the primary trial, this did not come without added complexity. Activation of the ancillary studies happened after the SELECT randomizations had begun resulting in accrual problems to some of the studies. Study site participation in the ancillary trials varied greatly and depended on the interest of the study site principal investigator. Procedures for each were integrated into the primary trial and all monitoring was done by the SELECT Data and Safety Monitoring Committee. The impact of the early closure of the primary trial was different for each of the ancillary trials.
Conclusions: The ancillary studies allowed study sites to broaden the research opportunities for their participants. Their implementation was efficient because of the established infrastructure of the primary trial. Implementation of these ancillary trials took substantial planning and coordination but enriched the overall primary trial.
C1 [Goodman, Phyllis J.; Tangen, Catherine M.; Darke, Amy K.; Arnold, Kathryn B.] Fred Hutchinson Canc Res Ctr, SWOG Stat Ctr, 1100 Fairview Ave N,M3-C102, Seattle, WA 98109 USA.
[Hartline, JoAnn; Yee, Monica; Anderson, Karen; Crowley, John J.] SWOG Stat Ctr, Canc Res & Biostat, Seattle, WA USA.
[Caban-Holt, Allison] Univ Kentucky, Sanders Brown Ctr Aging, Lexington, KY 40536 USA.
[Christen, William G.] Harvard Med Sch, Brigham & Womens Hosp, Boston, MA USA.
[Cassano, Patricia A.] Cornell Univ, Div Nutr Sci, Ithaca, NY 14853 USA.
[Lance, Peter] Univ Arizona, Arizona Canc Ctr, Phoenix, AZ USA.
[Klein, Eric A.] Cleveland Clin, Glickman Urol & Kidney Inst, Cleveland, OH 44106 USA.
[Minasian, Lori M.] NCI, Canc Prevent Div, Bethesda, MD 20892 USA.
[Meyskens, Frank L.] Univ Calif Irvine, Orange, CA 92668 USA.
RP Goodman, PJ (reprint author), Fred Hutchinson Canc Res Ctr, SWOG Stat Ctr, 1100 Fairview Ave N,M3-C102, Seattle, WA 98109 USA.
EM pgoodman@fredhutch.org
FU Public Health Service - National Cancer Institute, National Institutes
of Health, Department of Health and Human Services [CA37429, UM1
CA182883]; National Center for Complementary and Alternative Medicine
(National Institutes of Health); NIA [R01 AG19241]; NEI [EY014418];
NHLBI [RO1HL071022]; NCI [R01CA124862]
FX This work was supported in part by Public Health Service Cooperative
Agreement grant CA37429 and UM1 CA182883 awarded by the National Cancer
Institute, National Institutes of Health, Department of Health and Human
Services, and in part by the National Center for Complementary and
Alternative Medicine (National Institutes of Health). It was also
supported in part by NIA R01 AG19241 (PREADVISE), NEI EY014418 (SEE),
NHLBI (RO1HL071022) (RAS) and NCI R01CA124862 (ACP). Study agents and
packaging were provided by Perrigo Company (Allegan, MI, USA), Sabinsa
Corporation (Piscataway, NJ, USA), Tishcon Corporation (Westbury, NY,
USA) and DSM Nutritional Products Inc. (Parsipanny, NJ, USA).
NR 12
TC 0
Z9 0
U1 6
U2 6
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1745-6215
J9 TRIALS
JI Trials
PD AUG 12
PY 2016
VL 17
AR 400
DI 10.1186/s13063-016-1524-9
PG 10
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA DT2ZE
UT WOS:000381349500001
PM 27519183
ER
PT J
AU Bucher, S
Konana, O
Liechty, E
Garces, A
Gisore, P
Marete, I
Tenge, C
Shipala, E
Wright, L
Esamai, F
AF Bucher, Sherri
Konana, Olive
Liechty, Edward
Garces, Ana
Gisore, Peter
Marete, Irene
Tenge, Constance
Shipala, Evelyn
Wright, Linda
Esamai, Fabian
TI Self-reported practices among traditional birth attendants surveyed in
western Kenya: a descriptive study
SO BMC PREGNANCY AND CHILDBIRTH
LA English
DT Article
DE Traditional birth attendant; Maternal-newborn health; Delivery
practices; Africa; Kenya; Health policy
ID NEWBORN HEALTH REGISTRY; HELPING BABIES BREATHE; PREVENT POSTPARTUM
HEMORRHAGE; RESOURCE-LIMITED SETTINGS; IN-HOME BIRTHS; MATERNAL HEALTH;
GLOBAL-NETWORK; NEONATAL-MORTALITY; INCOME COUNTRIES; CONTROLLED-TRIAL
AB Background: The high rate of home deliveries conducted by unskilled birth attendants in resource-limited settings is an important global health issue because it is believed to be a significant contributing factor to maternal and newborn mortality. Given the large number of deliveries that are managed by unskilled or traditional birth attendants outside of health facilities, and the fact that there is on-going discussion regarding the role of traditional birth attendants in the maternal newborn health (MNH) service continuum, we sought to ascertain the practices of traditional birth attendants in our catchment area. The findings of this descriptive study might help inform conversations regarding the roles that traditional birth attendants can play in maternal-newborn health care.
Methods: A structured questionnaire was used in a survey that included one hundred unskilled birth attendants in western Kenya. Descriptive statistics were employed.
Results: Inappropriate or outdated practices were reported in relation to some obstetric complications and newborn care. Encouraging results were reported with regard to positive relationships that traditional birth attendants have with their local health facilities. Furthermore, high rates of referral to health facilities was reported for many common obstetric emergencies and similar rates for reporting of pregnancy outcomes to village elders and chiefs.
Conclusions: Potentially harmful or outdated practices with regard to maternal and newborn care among traditional birth attendants in western Kenya were revealed by this study. There were high rates of traditional birth attendant referrals of pregnant mothers with obstetric complications to health facilities. Policy makers may consider re-educating and re-defining the roles and responsibilities of traditional birth attendants in maternal and neonatal health care based on the findings of this survey.
C1 [Bucher, Sherri; Konana, Olive; Liechty, Edward] Indiana Univ Sch Med, Sect Neonatal Perinatal Med, Dept Pediat, 699 Riley Hosp Dr,RR208, Indianapolis, IN 46202 USA.
[Garces, Ana] INSALUD, Guatemala City, Guatemala.
[Gisore, Peter; Marete, Irene; Tenge, Constance; Esamai, Fabian] Moi Univ, Sch Med, Dept Paediat & Child Hlth, Eldoret, Kenya.
[Shipala, Evelyn] Moi Teaching & Referral Hosp, Eldoret, Kenya.
[Wright, Linda] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Ctr Res Mothers & Children, Bethesda, MD USA.
RP Bucher, S (reprint author), Indiana Univ Sch Med, Sect Neonatal Perinatal Med, Dept Pediat, 699 Riley Hosp Dr,RR208, Indianapolis, IN 46202 USA.
EM shbucher@iu.edu
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development of the National Institutes of Health [U01 HD058326, U01
HD040657, U01 HD040636]; Bill & Melinda Gates Foundation
FX This study was funded by the Eunice Kennedy Shriver National Institute
of Child Health and Human Development of the National Institutes of
Health under Award Numbers U01 HD058326 (Kenya), U01 HD040657
(Guatemala), and U01 HD040636 (RTI). This study was supported in part by
a grant from the Bill & Melinda Gates Foundation. The investigators were
solely responsible for the study design, data collection, analysis,
interpretation of the data, and writing of the manuscript, without
influence from the funding agencies.
NR 55
TC 0
Z9 0
U1 6
U2 6
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2393
J9 BMC PREGNANCY CHILDB
JI BMC Pregnancy Childbirth
PD AUG 12
PY 2016
VL 16
AR 219
DI 10.1186/s12884-016-1007-8
PG 7
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA DT4UK
UT WOS:000381476400002
PM 27514379
ER
PT J
AU Toombes, GES
Swartz, KJ
AF Toombes, Gilman E. S.
Swartz, Kenton J.
TI Twists and turns in gating ion channels with voltage The EAG potassium
channel may use an alternative voltage-dependent gating mechanism
SO SCIENCE
LA English
DT Editorial Material
ID CRYSTAL-STRUCTURE; DOMAINS
C1 [Toombes, Gilman E. S.; Swartz, Kenton J.] NINDS, Mol Physiol & Biophys Sect, Porter Neurosci Res Ctr, NIH, Bethesda, MD 20892 USA.
RP Swartz, KJ (reprint author), NINDS, Mol Physiol & Biophys Sect, Porter Neurosci Res Ctr, NIH, Bethesda, MD 20892 USA.
EM kenton.swartz@nih.gov
NR 15
TC 0
Z9 0
U1 5
U2 8
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 AUG 12
PY 2016
VL 353
IS 6300
BP 646
EP 647
DI 10.1126/science.aah4194
PG 2
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DT5ZC
UT WOS:000381561200018
PM 27516583
ER
PT J
AU Hoenen, T
Groseth, A
Safronetz, D
Wollenberg, K
Feldmann, H
AF Hoenen, Thomas
Groseth, Allison
Safronetz, David
Wollenberg, Kurt
Feldmann, Heinz
TI Response to Comment on "Mutation rate and genotype variation of Ebola
virus from Mali case sequences"
SO SCIENCE
LA English
DT Editorial Material
ID SIERRA-LEONE; OUTBREAK; TRANSMISSION; MACAQUES; DISEASE; STRAIN
AB Rambaut et al. show that the erratum to our report on Ebola virus Makona evolution not only corrected sample dates modified by others in GenBank but also corrected an additional transcriptional error in our original analysis. We agree with their observation that both factors contributed to our revised evolutionary rate estimate but continue to stand by our revised estimate and conclusions.
C1 [Hoenen, Thomas; Groseth, Allison; Safronetz, David; Feldmann, Heinz] NIAID, Virol Lab, Div Intramural Res, NIH,Rocky Mt Labs, Hamilton, MT USA.
[Wollenberg, Kurt] NIAID, Bioinformat & Computat Biosci Branch, NIH, Bethesda, MD USA.
RP Feldmann, H (reprint author), NIAID, Virol Lab, Div Intramural Res, NIH,Rocky Mt Labs, Hamilton, MT USA.
EM feldmannh@niaid.nih.gov
OI Hoenen, Thomas/0000-0002-5829-6305
FU Intramural NIH HHS
NR 13
TC 0
Z9 0
U1 1
U2 1
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 AUG 12
PY 2016
VL 353
IS 6300
DI 10.1126/science.aaf4561
PG 1
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DT5ZC
UT WOS:000381561200030
PM 27516593
ER
PT J
AU Enose-Akahata, Y
Caruso, B
Haner, B
Charlip, E
Nair, G
Massoud, R
Billioux, BJ
Ohayon, J
Switzer, WM
Jacobson, S
AF Enose-Akahata, Yoshimi
Caruso, Breanna
Haner, Benjamin
Charlip, Emily
Nair, Govind
Massoud, Raya
Billioux, Bridgette J.
Ohayon, Joan
Switzer, William M.
Jacobson, Steven
TI Development of neurologic diseases in a patient with primate T
lymphotropic virus type 1 (PTLV-1)
SO RETROVIROLOGY
LA English
DT Article
DE HTLV; PTLV; STLV; HAM/TSP
ID TROPICAL SPASTIC PARAPARESIS; I-ASSOCIATED MYELOPATHY; HTLV-I;
NONHUMAN-PRIMATES; PERIPHERAL-BLOOD; MOLECULAR EPIDEMIOLOGY;
CEREBROSPINAL-FLUID; HAM/TSP PATIENTS; CENTRAL-AFRICA; COTE-DIVOIRE
AB Background: Virus transmission from various wild and domestic animals contributes to an increased risk of emerging infectious diseases in human populations. HTLV-1 is a human retrovirus associated with acute T-cell leukemia and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). HTLV-1 originated from ancient zoonotic transmission from nonhuman primates, although cases of zoonotic infections continue to occur. Similar to HTLV-1, the simian counterpart, STLV-1, causes chronic infection and leukemia and lymphoma in naturally infected monkeys, and combined are called primate T-lymphotropic viruses (PTLV-1). However, other clinical syndromes typically seen in humans such as a chronic progressive myelopathy have not been observed in nonhuman primates. Little is known about the development of neurologic and inflammatory diseases in human populations infected with STLV-1-like viruses following nonhuman primate exposure.
Results: We performed detailed laboratory analyses on an HTLV-1 seropositive patient with typical HAM/TSP who was born in Liberia and now resides in the United States. Using a novel droplet digital PCR for the detection of the HTLV-1 tax gene, the proviral load in PBMC and cerebrospinal fluid cells was 12.98 and 51.68 %, respectively; however, we observed a distinct difference in fluorescence amplitude of the positive droplet population suggesting possible mutations in proviral DNA. A complete PTLV-1 proviral genome was amplified from the patient's PBMC DNA using an overlapping PCR strategy. Phylogenetic analysis of the envelope and LTR sequences showed the virus was highly related to PTLV-1 from sooty mangabey monkeys (smm) and humans exposed via nonhuman primates in West Africa.
Conclusions: These results demonstrate the patient is infected with a simian variant of PTLV-1, suggesting for the first time that PTLV-1smm infection in humans may be associated with a chronic progressive neurologic disease.
C1 [Enose-Akahata, Yoshimi; Caruso, Breanna; Haner, Benjamin; Charlip, Emily; Massoud, Raya; Billioux, Bridgette J.; Ohayon, Joan; Jacobson, Steven] NINDS, Viral Immunol Sect, Neuroimmunol Branch, NIH, 9000 Rockville Pike,Bldg 10 Room 5C-103, Bethesda, MD 20892 USA.
[Nair, Govind] NINDS, Translat Neuroradiol Unit, Neuroimmunol Branch, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
[Switzer, William M.] Ctr Dis Control & Prevent, Branch Lab, Div HIV AIDS, Natl Ctr HIV Hepatitis STD & TB Prevent, Atlanta, GA 30329 USA.
RP Jacobson, S (reprint author), NINDS, Viral Immunol Sect, Neuroimmunol Branch, NIH, 9000 Rockville Pike,Bldg 10 Room 5C-103, Bethesda, MD 20892 USA.
EM jacobsons@ninds.nih.gov
FU Intramural Research Program of the NINDS, NIH
FX This research was supported by the Intramural Research Program of the
NINDS, NIH.
NR 45
TC 1
Z9 1
U1 1
U2 2
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1742-4690
J9 RETROVIROLOGY
JI Retrovirology
PD AUG 12
PY 2016
VL 13
AR 56
DI 10.1186/s12977-016-0290-9
PG 13
WC Virology
SC Virology
GA DT1RX
UT WOS:000381260900001
PM 27519553
ER
PT J
AU Eveland, M
Brokamp, GA
Lue, CH
Harbison, ST
Leips, J
De Luca, M
AF Eveland, Matthew
Brokamp, Gabrielle A.
Lue, Chia-Hua
Harbison, Susan T.
Leips, Jeff
De Luca, Maria
TI Knockdown expression of Syndecan in the fat body impacts nutrient
metabolism and the organismal response to environmental stresses in
Drosophila melanogaster
SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
LA English
DT Article
DE Fat body; Syndecans; Metabolism; Survival; AKT; ERK1/2
ID EXTENDS LIFE-SPAN; ENERGY-METABOLISM; GENE-EXPRESSION; CROSS-TALK;
OBESITY; LOCALIZATION; TOLERANCE; PATHWAYS; BEHAVIOR; WEIGHT
AB The heparan sulfate proteoglycan syndecans are transmembrane proteins involved in multiple physiological processes, including cell-matrix adhesion and inflammation. Recent evidence from model systems and humans suggest that syndecans have a role in energy balance and nutrient metabolism regulation. However, much remains to be learned about the mechanisms through which syndecans influence these phenotypes. Previously, we reported that Drosophila melanogaster Syndecan (Sdc) mutants had reduced metabolic activity compared to controls. Here, we knocked down endogenous Sdc expression in the fat body (the functional equivalent of mammalian adipose tissue and liver) to investigate whether the effects on metabolism originate from this tissue. We found that knocking down Sdc in the fat body leads to flies with higher levels of glycogen and fat and that survive longer during starvation, likely due to their extra energy reserves and an increase in gluconeogenesis. However, compared to control flies, they are also more sensitive to environmental stresses (e.g. bacterial infection and cold) and have reduced metabolic activity under normal feeding conditions. Under the same conditions, fat-body Sdc reduction enhances expression of genes involved in glyceroneogenesis and gluconeogenesis and induces a drastic decrease in phosphorylation levels of AI CT and extracellular signal regulated kinase 1/2 (ERK1/2). Altogether, these findings strongly suggest that Drosophila fat body Sdc is involved in a mechanism that shifts resources to different physiological functions according to nutritional status. (C) 2016 Elsevier Inc. All rights reserved.
C1 [Eveland, Matthew; Brokamp, Gabrielle A.; De Luca, Maria] Univ Alabama Birmingham, Dept Nutr Sci, Birmingham, AL 35294 USA.
[Lue, Chia-Hua; Leips, Jeff] Univ Maryland Baltimore Cty, Dept Biol Sci, Baltimore, MD 21228 USA.
[Harbison, Susan T.] NHLBI, Lab Syst Genet, Bldg 10, Bethesda, MD 20892 USA.
[Eveland, Matthew] Columbia Univ, Dept Biochem & Mol Biophys, Med Ctr, New York, NY 10032 USA.
RP De Luca, M (reprint author), Univ Alabama Birmingham, Webb 451-1530 3rd Ave S, Birmingham, AL 35294 USA.
EM mdeluca2@uab.edu
RI Harbison, Susan/P-2577-2016
OI Harbison, Susan/0000-0001-7233-0947
FU National Institutes of Health [R01 DK084219]; UAB Diabetes Research
Center Pilot & Feasibility Program [P30 DK079626]
FX We are grateful to Michael Crowley and David K. Crossman at the UAB
Heflin Center for Genomic Sciences for performing RNA sequencing
analysis. This work was supported by the National Institutes of Health
(R01 DK084219) and UAB Diabetes Research Center Pilot & Feasibility
Program (P30 DK079626) grants to MD.
NR 31
TC 1
Z9 1
U1 5
U2 7
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0006-291X
EI 1090-2104
J9 BIOCHEM BIOPH RES CO
JI Biochem. Biophys. Res. Commun.
PD AUG 12
PY 2016
VL 477
IS 1
BP 103
EP 108
DI 10.1016/j.bbrc.2016.06.027
PG 6
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA DS0OQ
UT WOS:000380297000016
PM 27289019
ER
PT J
AU Yeo, S
Hodgkinson, CA
Zhou, ZF
Jung, J
Leung, M
Yuan, QP
Goldman, D
AF Yeo, Seungeun
Hodgkinson, Colin A.
Zhou, Zhifeng
Jung, Jeesun
Leung, Ming
Yuan, Qiaoping
Goldman, David
TI The abundance of cis-acting loci leading to differential allele
expression in F1 mice and their relationship to loci harboring genes
affecting complex traits
SO BMC GENOMICS
LA English
DT Article
DE RNA-Seq; Differential allelic expression; cis-acting loci; Quantitative
trait loci
ID INBRED MOUSE STRAINS; IMPRINTED GENES; MONOALLELIC EXPRESSION; VOLUNTARY
CONSUMPTION; RNA-SEQ; MICE; IDENTIFICATION; BRAIN; PHENOTYPES; ETHANOL
AB Background: Genome-wide surveys have detected cis-acting quantitative trait loci altering levels of RNA transcripts (RNA-eQTLs) by associating SNV alleles to transcript levels. However, the sensitivity and specificity of detection of cis- expression quantitative trait loci (eQTLs) by genetic approaches, reliant as it is on measurements of transcript levels in recombinant inbred strains or offspring from arranged crosses, is unknown, as is their relationship to QTL's for complex phenotypes.
Results: We used transcriptome-wide differential allele expression (DAE) to detect cis-eQTLs in forebrain and kidney from reciprocal crosses between three mouse inbred strains, 129S1/SvlmJ, DBA/2J, and CAST/EiJ and C57BL/6 J. Two of these crosses were previously characterized for cis-eQTLs and QTLs for various complex phenotypes by genetic analysis of recombinant inbred (RI) strains. 5.4 %, 1.9 % and 1.5 % of genes assayed in forebrain of B6/129SF1, B6/DBAF1, and B6/CASTF1 mice, respectively, showed differential allelic expression, indicative of cis-acting alleles at these genes. Moreover, the majority of DAE QTLs were observed to be tissue-specific with only a small fraction showing cis-effects in both tissues. Comparing DAE QTLs in F1 mice to cis-eQTLs previously mapped in RI strains we observed that many of the cis-eQTLs were not confirmed by DAE. Additionally several novel DAE-QTLs not identified as cis-eQTLs were identified suggesting that there are differences in sensitivity and specificity for QTL detection between the two methodologies. Strain specific DAE QTLs in B6/DBAF1 mice were located in excess at candidate genes for alcohol use disorders, seizures, and angiogenesis previously implicated by genetic linkage in C57BL/6J x DBA/2JF2 mice or BXD RI strains.
Conclusions: Via a survey for differential allele expression in F1 mice, a substantial proportion of genes were found to have alleles altering expression in cis-acting fashion. Comparing forebrain and kidney, many or most of these alleles were tissue-specific in action. The identification of strain specific DAE QTLs, can assist in assessment of candidate genes located within the large intervals associated with trait QTLs.
C1 [Yeo, Seungeun; Hodgkinson, Colin A.; Zhou, Zhifeng; Leung, Ming; Yuan, Qiaoping; Goldman, David] NIAAA, Neurogenet Lab, NIH, Bethesda, MD 20852 USA.
[Jung, Jeesun] NIAAA, Lab Epidemiol & Biometry, NIH, Bethesda, MD 20852 USA.
RP Goldman, D (reprint author), NIAAA, Neurogenet Lab, NIH, Bethesda, MD 20852 USA.
EM davidgoldman@mail.nih.gov
FU National Institutes of Health [AA000301]
FX Financial support was provided by the National Institutes of Health
(AA000301)
NR 51
TC 1
Z9 1
U1 0
U2 0
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2164
J9 BMC GENOMICS
JI BMC Genomics
PD AUG 11
PY 2016
VL 17
AR 620
DI 10.1186/s12864-016-2922-9
PG 15
WC Biotechnology & Applied Microbiology; Genetics & Heredity
SC Biotechnology & Applied Microbiology; Genetics & Heredity
GA DX0JP
UT WOS:000384047900012
PM 27515598
ER
PT J
AU Wolfe, GI
Kaminski, HJ
Aban, IB
Minisman, G
Kuo, HC
Marx, A
Strobel, P
Mazia, C
Oger, J
Cea, JG
Heckmann, JM
Evoli, A
Nix, W
Ciafaloni, E
Antonini, G
Witoonpanich, R
King, JO
Beydoun, SR
Chalk, CH
Barboi, AC
Amato, AA
Shaibani, AI
Katirji, B
Lecky, BRF
Buckley, C
Vincent, A
Dias-Tosta, E
Yoshikawa, H
Waddington-Cruz, M
Pulley, MT
Rivner, MH
Kostera-Pruszczyk, A
Pascuzzi, RM
Jackson, CE
Ramos, GSG
Verschuuren, JJGM
Massey, JM
Kissel, JT
Werneck, LC
Benatar, M
Barohn, RJ
Tandan, R
Mozaffar, T
Conwit, R
Odenkirchen, J
Sonett, JR
Jaretzki, A
Newsom-Davis, J
Cutter, GR
AF Wolfe, G. I.
Kaminski, H. J.
Aban, I. B.
Minisman, G.
Kuo, H-C
Marx, A.
Strobel, P.
Mazia, C.
Oger, J.
Cea, J. G.
Heckmann, J. M.
Evoli, A.
Nix, W.
Ciafaloni, E.
Antonini, G.
Witoonpanich, R.
King, J. O.
Beydoun, S. R.
Chalk, C. H.
Barboi, A. C.
Amato, A. A.
Shaibani, A. I.
Katirji, B.
Lecky, B. R. F.
Buckley, C.
Vincent, A.
Dias-Tosta, E.
Yoshikawa, H.
Waddington-Cruz, M.
Pulley, M. T.
Rivner, M. H.
Kostera-Pruszczyk, A.
Pascuzzi, R. M.
Jackson, C. E.
Ramos, G. S. Garcia
Verschuuren, J. J. G. M.
Massey, J. M.
Kissel, J. T.
Werneck, L. C.
Benatar, M.
Barohn, R. J.
Tandan, R.
Mozaffar, T.
Conwit, R.
Odenkirchen, J.
Sonett, J. R.
Jaretzki, A., III
Newsom-Davis, J.
Cutter, G. R.
CA MGTX Study Grp
TI Randomized Trial of Thymectomy in Myasthenia Gravis
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID EXTENDED THYMECTOMY; THORACOSCOPIC THYMECTOMY; MYCOPHENOLATE-MOFETIL;
FOLLOW-UP; PREDNISONE; STANDARDS; SCORE
AB BACKGROUND
Thymectomy has been a mainstay in the treatment of myasthenia gravis, but there is no conclusive evidence of its benefit. We conducted a multicenter, randomized trial comparing thymectomy plus prednisone with prednisone alone.
METHODS
We compared extended transsternal thymectomy plus alternate-day prednisone with alternate-day prednisone alone. Patients 18 to 65 years of age who had generalized nonthymomatous myasthenia gravis with a disease duration of less than 5 years were included if they had Myasthenia Gravis Foundation of America clinical class II to IV disease (on a scale from I to V, with higher classes indicating more severe disease) and elevated circulating concentrations of acetylcholine-receptor antibody. The primary outcomes were the time-weighted average Quantitative Myasthenia Gravis score (on a scale from 0 to 39, with higher scores indicating more severe disease) over a 3-year period, as assessed by means of blinded rating, and the time-weighted average required dose of prednisone over a 3-year period.
RESULTS
A total of 126 patients underwent randomization between 2006 and 2012 at 36 sites. Patients who underwent thymectomy had a lower time-weighted average Quantitative Myasthenia Gravis score over a 3-year period than those who received prednisone alone (6.15 vs. 8.99, P < 0.001); patients in the thymectomy group also had a lower average requirement for alternate-day prednisone (44 mg vs. 60 mg, P < 0.001). Fewer patients in the thymectomy group than in the prednisone-only group required immunosuppression with azathioprine (17% vs. 48%, P < 0.001) or were hospitalized for exacerbations (9% vs. 37%, P < 0.001). The number of patients with treatment-associated complications did not differ significantly between groups (P = 0.73), but patients in the thymectomy group had fewer treatment-associated symptoms related to immunosuppressive medications (P < 0.001) and lower distress levels related to symptoms (P = 0.003).
CONCLUSIONS
Thymectomy improved clinical outcomes over a 3-year period in patients with nonthymomatous myasthenia gravis. (Funded by the National Institute of Neurological Disorders and Stroke and others; MGTX ClinicalTrials.gov number, NCT00294658.)
C1 [Wolfe, G. I.] Univ Buffalo, Jacobs Sch Med & Biomed Sci, Dept Neurol, 100 High St, Buffalo, NY 14203 USA.
[Ciafaloni, E.] Univ Rochester, Med Ctr, Dept Neurol, Rochester, NY 14627 USA.
[Sonett, J. R.; Jaretzki, A., III] Columbia Univ, Sect Gen Thorac Surg, Med Ctr, New York, NY USA.
[Kaminski, H. J.] George Washington Univ, Dept Neurol, Sch Med & Hlth Sci, Washington, DC USA.
[Aban, I. B.; Minisman, G.; Kuo, H-C; Cutter, G. R.] Univ Alabama Birmingham, Dept Biostat, Birmingham, AL 35294 USA.
[Marx, A.] Heidelberg Univ, Inst Pathol, Univ Med Ctr Mannheim, Mannheim, Germany.
[Strobel, P.] Univ Gottingen, Inst Pathol, Gottingen, Germany.
[Nix, W.] Johannes Gutenberg Univ Mainz, Dept Neurol, Mainz, Germany.
[Mazia, C.] Univ Buenos Aires, Dept Neurol, Buenos Aires, DF, Argentina.
[Oger, J.] Univ British Columbia, Div Neurol, Vancouver, BC, Canada.
[Chalk, C. H.] McGill Univ, Dept Neurol, Montreal, PQ, Canada.
[Cea, J. G.] Univ Chile, Dept Neurol, Santiago, Chile.
[Heckmann, J. M.] Univ Cape Town, Div Neurol, Dept Med, Cape Town, South Africa.
[Evoli, A.] Catholic Univ, Dept Neurol, Rome, Italy.
[Antonini, G.] Sapienza Univ Rome, Dept Neurosci Mental Hlth & Sensory Organs, Rome, Italy.
[Witoonpanich, R.] Mahidol Univ, Div Neurol, Ramathibodi Hosp, Bangkok, Thailand.
[King, J. O.] Univ Melbourne, Dept Neurol, Melbourne, Vic, Australia.
[Beydoun, S. R.] Univ Southern Calif, Dept Neurol, Los Angeles, CA USA.
[Mozaffar, T.] Univ Calif Irvine, Dept Neurol, Med Ctr, Orange, CA 92668 USA.
[Barboi, A. C.] Med Coll Wisconsin, Dept Neurol, Milwaukee, WI 53226 USA.
[Amato, A. A.] Harvard Med Sch, Dept Neurol, Boston, MA USA.
[Shaibani, A. I.] Nerve & Muscle Ctr Texas, Houston, TX USA.
[Jackson, C. E.] Univ Texas Hlth Sci Ctr San Antonio, Dept Neurol, San Antonio, TX 78229 USA.
[Katirji, B.] Case Western Reserve Univ, Dept Neurol, Cleveland, OH 44106 USA.
[Kissel, J. T.] Ohio State Univ, Dept Neurol, Wexner Med Ctr, Columbus, OH 43210 USA.
[Lecky, B. R. F.] Walton Ctr Neurol & Neurosurg, Liverpool, Merseyside, England.
[Buckley, C.; Vincent, A.; Newsom-Davis, J.] Univ Oxford, Nuffield Dept Clin Neurosci, Oxford, England.
[Dias-Tosta, E.] Univ Brasilia, Neurol Unit, Brasilia, DF, Brazil.
[Waddington-Cruz, M.] Fed Univ, Dept Neurol, Rio De Janeiro, Brazil.
[Werneck, L. C.] Univ Fed Parana, Dept Neurol, Curitiba, Parana, Brazil.
[Yoshikawa, H.] Kanazawa Univ, Dept Neurol, Kanazawa, Ishikawa, Japan.
[Pulley, M. T.] Univ Florida, Dept Neurol, Jacksonville, FL USA.
[Benatar, M.] Univ Miami, Dept Neurol, Miami, FL USA.
[Rivner, M. H.] Georgia Regents Univ, Dept Neurol, Augusta, GA USA.
[Kostera-Pruszczyk, A.] Med Univ Warsaw, Dept Neurol, Warsaw, Poland.
[Pascuzzi, R. M.] Indiana Sch Med, Dept Neurol, Indianapolis, IN USA.
[Ramos, G. S. Garcia] Inst Nacl Nutr, Dept Neurol & Psychiat, Tlalpan, Mexico.
[Verschuuren, J. J. G. M.] Leiden Univ Med Ctr, Dept Neurol, Leiden, Netherlands.
[Massey, J. M.] Duke Univ, Med Ctr, Dept Neurol, Durham, NC USA.
[Barohn, R. J.] Univ Kansas, Med Ctr, Dept Neurol, Kansas City, KS 66103 USA.
[Tandan, R.] Univ Vermont, Coll Med, Dept Neurol Sci, Burlington, VT USA.
[Conwit, R.; Odenkirchen, J.] NINDS, Div Extramural Res, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
RP Wolfe, GI (reprint author), Univ Buffalo, Jacobs Sch Med & Biomed Sci, Dept Neurol, 100 High St, Buffalo, NY 14203 USA.
EM gilwolfe@buffalo.edu
OI Heckmann, Jeannine/0000-0002-8999-718X; Venuta,
Federico/0000-0001-9296-877X
FU National Institute of Neurological Disorders and Stroke
FX Funded by the National Institute of Neurological Disorders and Stroke
and others; MGTX ClinicalTrials.gov number, NCT00294658.
NR 32
TC 19
Z9 19
U1 7
U2 7
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 AUG 11
PY 2016
VL 375
IS 6
BP 511
EP 522
DI 10.1056/NEJMoa1602489
PG 12
WC Medicine, General & Internal
SC General & Internal Medicine
GA DU4OT
UT WOS:000382193100004
PM 27509100
ER
PT J
AU Silva, NCS
Vale, VF
Franco, PF
Gontijo, NF
Valenzuela, JG
Pereira, MH
Sant'Anna, MRV
Rodrigues, DS
Lima, WS
Fux, B
Araujo, RN
AF Silva, Naylene C. S.
Vale, Vladimir F.
Franco, Paula F.
Gontijo, Nelder F.
Valenzuela, Jesus G.
Pereira, Marcos H.
Sant'Anna, Mauricio R. V.
Rodrigues, Daniel S.
Lima, Walter S.
Fux, Blima
Araujo, Ricardo N.
TI Saliva of Rhipicephalus (Boophilus) microplus (Acari: Ixodidae) inhibits
classical and alternative complement pathways
SO PARASITES & VECTORS
LA English
DT Article
DE Rhipicephalus (Boophilus) microplus; Saliva; Complement inhibition;
Classical pathway; Alternative pathway
ID MANNOSE-BINDING LECTIN; IXODES-DAMMINI; ANTICOMPLEMENT PROTEINS; C3
CONVERTASE; TICK; CALRETICULIN; SYSTEM; CATTLE; ACTIVATION; MECHANISM
AB Background: Rhipicephalus (Boophilus) microplus is the main ectoparasite affecting livestock worldwide. For a successful parasitism, ticks need to evade several immune responses of their hosts, including the activation of the complement system. In spite of the importance of R. microplus, previous work only identified one salivary molecule that blocks the complement system. The current study describes complement inhibitory activities induced by R. microplus salivary components and mechanisms elicited by putative salivary proteins on both classical and alternative complement pathways.
Results: We found that R. microplus saliva from fully-and partially engorged females was able to inhibit both pathways. Saliva acts strongly at the initial steps of both complement activation pathways. In the classical pathway, the saliva blocked C4 cleavage, and hence, deposition of C4b on the activation surface, suggesting that the inhibition occurs at some point between C1q and C4. In the alternative pathway, saliva acts by binding to initial components of the cascade (C3b and properdin) thereby preventing the C3 convertase formation and reducing C3b production and deposition as well as cleavage of factor B. Saliva has no effect on formation or decay of the C6 to C8 components of the membrane attack complex.
Conclusion: The saliva of R. microplus is able to inhibit the early steps of classical and alternative pathways of the complement system. Saliva acts by blocking C4 cleavage and deposition of C4b on the classical pathway activation surface and, in the alternative pathway, saliva bind to initial components of the cascade (C3b and properdin) thereby preventing the C3 convertase formation and the production and deposition of additional C3b.
C1 [Silva, Naylene C. S.; Vale, Vladimir F.; Franco, Paula F.; Gontijo, Nelder F.; Pereira, Marcos H.; Sant'Anna, Mauricio R. V.; Lima, Walter S.; Araujo, Ricardo N.] Univ Fed Minas Gerais, Dept Parasitol, Lab Fisiol Insetos Hematofagos, Belo Horizonte, MG, Brazil.
[Vale, Vladimir F.] Fiocruz MS, Inst Oswaldo Cruz, Lab Simulideos & Oncocercose, Rio De Janeiro, RJ, Brazil.
[Gontijo, Nelder F.; Pereira, Marcos H.] Inst Nacl Ciencia & Tecnol Entomol Mol, BR-21941591 Rio De Janeiro, Brazil.
[Valenzuela, Jesus G.] NIAID, Vector Mol Biol Sect, LMVR, NIH, Rockville, MD USA.
[Rodrigues, Daniel S.] Empresa Pesquisa Agr Minas Gerais, Rodovia MG 424 Km 64,Caixa Postal 295, BR-35701970 Prudente De Morais, MG, Brazil.
[Fux, Blima] Univ Fed Espirito Santo, Dept Patol, Vitoria, MG, Brazil.
RP Araujo, RN (reprint author), Univ Fed Minas Gerais, Dept Parasitol, Lab Fisiol Insetos Hematofagos, Belo Horizonte, MG, Brazil.
EM rnaraujo@icb.ufmg.br
FU Fundacao de Amparo a Pesquisa do Estado de Minas Gerais (FAPEMIG);
Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq);
INCT- Entomologia Molecular
FX The work was supported by Fundacao de Amparo a Pesquisa do Estado de
Minas Gerais (FAPEMIG), Conselho Nacional de Desenvolvimento Cientifico
e Tecnologico (CNPq) and INCT- Entomologia Molecular.
NR 55
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 1756-3305
J9 PARASITE VECTOR
JI Parasites Vectors
PD AUG 11
PY 2016
VL 9
AR 445
DI 10.1186/s13071-016-1726-8
PG 14
WC Parasitology
SC Parasitology
GA DW7NJ
UT WOS:000383837500001
PM 27515662
ER
PT J
AU Horvath, S
Gurven, M
Levine, ME
Trumble, BC
Kaplan, H
Allayee, H
Ritz, BR
Chen, B
Lu, AT
Rickabaugh, TM
Jamieson, BD
Sun, D
Li, SX
Chen, W
Quintana-Murci, L
Fagny, M
Kobor, MS
Tsao, PS
Reiner, AP
Edlefsen, KL
Absher, D
Assimes, TL
AF Horvath, Steve
Gurven, Michael
Levine, Morgan E.
Trumble, Benjamin C.
Kaplan, Hillard
Allayee, Hooman
Ritz, Beate R.
Chen, Brian
Lu, Ake T.
Rickabaugh, Tammy M.
Jamieson, Beth D.
Sun, Dianjianyi
Li, Shengxu
Chen, Wei
Quintana-Murci, Lluis
Fagny, Maud
Kobor, Michael S.
Tsao, Philip S.
Reiner, Alexander P.
Edlefsen, Kerstin L.
Absher, Devin
Assimes, Themistocles L.
TI An epigenetic clock analysis of race/ethnicity, sex, and coronary heart
disease
SO GENOME BIOLOGY
LA English
DT Article
DE DNA methylation; Epigenetic clock; Race; Gender; Aging; Coronary heart
disease; Hispanic paradox; Black/white mortality cross-over
ID DNA METHYLATION AGE; HUMAN BRAIN; ALZHEIMERS-DISEASE; TELOMERE LENGTH;
PARKINSONS-DISEASE; AFRICAN-AMERICANS; UNITED-STATES; HUMAN TISSUES;
ALL-CAUSE; T-CELLS
AB Background: Epigenetic biomarkers of aging (the "epigenetic clock") have the potential to address puzzling findings surrounding mortality rates and incidence of cardio-metabolic disease such as: (1) women consistently exhibiting lower mortality than men despite having higher levels of morbidity; (2) racial/ethnic groups having different mortality rates even after adjusting for socioeconomic differences; (3) the black/white mortality cross-over effect in late adulthood; and (4) Hispanics in the United States having a longer life expectancy than Caucasians despite having a higher burden of traditional cardio-metabolic risk factors.
Results: We analyzed blood, saliva, and brain samples from seven different racial/ethnic groups. We assessed the intrinsic epigenetic age acceleration of blood (independent of blood cell counts) and the extrinsic epigenetic aging rates of blood (dependent on blood cell counts and tracks the age of the immune system). In blood, Hispanics and Tsimane Amerindians have lower intrinsic but higher extrinsic epigenetic aging rates than Caucasians. African-Americans have lower extrinsic epigenetic aging rates than Caucasians and Hispanics but no differences were found for the intrinsic measure. Men have higher epigenetic aging rates than women in blood, saliva, and brain tissue.
Conclusions: Epigenetic aging rates are significantly associated with sex, race/ethnicity, and to a lesser extent with CHD risk factors, but not with incident CHD outcomes. These results may help elucidate lower than expected mortality rates observed in Hispanics, older African-Americans, and women.
C1 [Horvath, Steve; Levine, Morgan E.; Lu, Ake T.] Univ Calif Los Angeles, David Geffen Sch Med, Human Genet, Los Angeles, CA 90095 USA.
[Horvath, Steve] Univ Calif Los Angeles, Sch Publ Hlth, Biostat, Los Angeles, CA 90095 USA.
[Gurven, Michael; Trumble, Benjamin C.] Univ Calif Santa Barbara, Dept Anthropol, Santa Barbara, CA 93106 USA.
[Kaplan, Hillard] Univ New Mexico, Dept Anthropol, Albuquerque, NM 87131 USA.
[Allayee, Hooman] Univ Southern Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90089 USA.
[Allayee, Hooman] Univ Southern Calif, Keck Sch Med, Inst Med Genet, Los Angeles, CA 90089 USA.
[Ritz, Beate R.] Univ Calif Los Angeles, Fielding Sch Publ Hlth, Dept Epidemiol, Los Angeles, CA 90095 USA.
[Chen, Brian] NIA, Longitudinal Studies Sect, Translat Gerontol Branch, NIH, Baltimore, MD 21224 USA.
[Rickabaugh, Tammy M.; Jamieson, Beth D.] Univ Calif Los Angeles, AIDS Inst, Dept Med, Div Hematol Oncol, Los Angeles, CA USA.
[Sun, Dianjianyi; Li, Shengxu; Chen, Wei] Tulane Univ, Dept Epidemiol, New Orleans, LA 70112 USA.
[Quintana-Murci, Lluis] CNRS, Inst Pasteur, URA3012, URA3012,Unit Human Evolutionary Genet, F-75015 Paris, France.
[Fagny, Maud] Harvard TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
[Fagny, Maud] Dana Farber Canc Inst, Dept Computat Biol & Biostat, Boston, MA 02115 USA.
[Kobor, Michael S.] Univ British Columbia, Ctr Mol Med & Therapeut, Child & Family Res Inst, Vancouver, BC V5Z 4H4, Canada.
[Kobor, Michael S.] Univ British Columbia, Dept Med Genet, Vancouver, BC V5Z 4H4, Canada.
[Tsao, Philip S.; Assimes, Themistocles L.] Stanford Univ, Sch Med, Dept Med, Stanford, CA 94305 USA.
[Tsao, Philip S.] VA Palo Alto Hlth Care Syst, Palo Alto, CA USA.
[Reiner, Alexander P.] Univ Washington, Fred Hutchinson Canc Res Ctr, Dept Epidemiol, Seattle, WA 98109 USA.
[Edlefsen, Kerstin L.] Univ Washington, Dept Lab Med, Seattle, WA 98195 USA.
[Absher, Devin] HudsonAlpha Inst Biotechnol, Huntsville, AL 35806 USA.
RP Horvath, S (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Human Genet, Los Angeles, CA 90095 USA.; Horvath, S (reprint author), Univ Calif Los Angeles, Sch Publ Hlth, Biostat, Los Angeles, CA 90095 USA.
EM shorvath@mednet.ucla.edu
RI Assimes, Themistocles/D-9696-2015;
OI Assimes, Themistocles/0000-0003-2349-0009; Horvath,
Steve/0000-0002-4110-3589; Fagny, Maud/0000-0002-7740-2521
FU NIH/NHLBI [60442456 BAA23]; National Institutes of Health NIH/NIA
[1U34AG051425-01]; National Heart, Lung, and Blood Institute, National
Institutes of Health, U.S. Department of Health and Human Services
[HHSN268201100046C, HHSN268201100001C, HHSN268201100002C,
HHSN268201100003C, HHSN268201100004C, HHSN271201100004C]; NIEHS
[RO1ES10544, R21 ES024356]; NIH/NIA [R01AG024119, R56AG02411];
[P30AG10161]; [R01AG17917]; [RF1AG15819]; [R01AG36042]
FX This study was supported by NIH/NHLBI 60442456 BAA23 (Assimes, Absher,
Horvath), National Institutes of Health NIH/NIA 1U34AG051425-01
(Horvath). The WHI program is funded by the National Heart, Lung, and
Blood Institute, National Institutes of Health, U.S. Department of
Health and Human Services through contracts HHSN268201100046C,
HHSN268201100001C, HHSN268201100002C, HHSN268201100003C,
HHSN268201100004C, and HHSN271201100004C. The PEG data were supported by
NIEHS RO1ES10544 (Ritz) and NIEHS R21 ES024356 (Horvath, Ritz). Gurven
and Trumble were funded by NIH/NIA R01AG024119 and R56AG02411. The
Religious Order study and Rush Memory and Aging Project (brain dataset
6) were funded by P30AG10161, R01AG17917, RF1AG15819, and R01AG36042.
NR 89
TC 4
Z9 4
U1 18
U2 27
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 AUG 11
PY 2016
VL 17
AR 171
DI 10.1186/s13059-016-1030-0
PG 22
WC Biotechnology & Applied Microbiology; Genetics & Heredity
SC Biotechnology & Applied Microbiology; Genetics & Heredity
GA DT8EH
UT WOS:000381721400001
PM 27511193
ER
PT J
AU Boritz, EA
Darko, S
Swaszek, L
Wolf, G
Wells, D
Wu, XL
Henry, AR
Laboune, F
Hu, JF
Ambrozak, D
Hughes, MS
Hoh, R
Casazza, JP
Vostal, A
Bunis, D
Nganou-Makamdop, K
Lee, JS
Migueles, SA
Koup, RA
Connors, M
Moir, S
Schacker, T
Maldarelli, F
Hughes, SH
Deeks, SG
Douek, DC
AF Boritz, Eli A.
Darko, Samuel
Swaszek, Luke
Wolf, Gideon
Wells, David
Wu, Xiaolin
Henry, Amy R.
Laboune, Farida
Hu, Jianfei
Ambrozak, David
Hughes, Marybeth S.
Hoh, Rebecca
Casazza, Joseph P.
Vostal, Alexander
Bunis, Daniel
Nganou-Makamdop, Krystelle
Lee, James S.
Migueles, Stephen A.
Koup, Richard A.
Connors, Mark
Moir, Susan
Schacker, Timothy
Maldarelli, Frank
Hughes, Stephen H.
Deeks, Steven G.
Douek, Daniel C.
TI Multiple Origins of Virus Persistence during Natural Control of HIV
Infection
SO CELL
LA English
DT Article
ID ACTIVE ANTIRETROVIRAL THERAPY; CD4(+) T-CELLS; ELITE SUPPRESSORS; LATENT
RESERVOIR; IN-VIVO; REPLICATION; PROLIFERATION; TYPE-1; LYMPHOCYTES;
ACTIVATION
AB Targeted HIV cure strategies require definition of the mechanisms that maintain the virus. Here, we tracked HIV replication and the persistence of infected CD4 T cells in individuals with natural virologic control by sequencing viruses, T cell receptor genes, HIV integration sites, and cellular transcriptomes. Our results revealed three mechanisms of HIV persistence operating within distinct anatomic and functional compartments. In lymph node, we detected viruses with genetic and transcriptional attributes of active replication in both T follicular helper (T-FH) cells and non-T-FH memory cells. In blood, we detected inducible proviruses of archival origin among highly differentiated, clonally expanded cells. Linking the lymph node and blood was a small population of circulating cells harboring inducible proviruses of recent origin. Thus, HIV replication in lymphoid tissue, clonal expansion of infected cells, and recirculation of recently infected cells act together to maintain the virus in HIV controllers despite effective antiviral immunity.
C1 [Boritz, Eli A.; Darko, Samuel; Swaszek, Luke; Wolf, Gideon; Henry, Amy R.; Laboune, Farida; Hu, Jianfei; Bunis, Daniel; Nganou-Makamdop, Krystelle; Lee, James S.; Douek, Daniel C.] NIAID, Human Immunol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Wells, David; Wu, Xiaolin] Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
[Ambrozak, David; Casazza, Joseph P.; Koup, Richard A.] NIAID, Immunol Lab, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Hughes, Marybeth S.] NCI, Thorac & Gastrointestinal Oncol Branch, NIH, Bethesda, MD 20892 USA.
[Hoh, Rebecca; Deeks, Steven G.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94110 USA.
[Migueles, Stephen A.; Connors, Mark; Moir, Susan] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA.
[Maldarelli, Frank; Hughes, Stephen H.] NCI, HIV Dynam & Replicat Program, NIH, Frederick, MD 21702 USA.
[Schacker, Timothy] Univ Minnesota, Dept Med, Program HIV Med, Minneapolis, MN 55455 USA.
RP Douek, DC (reprint author), NIAID, Human Immunol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
EM ddouek@mail.nih.gov
OI Jianfei, Hu/0000-0001-8458-6683
FU NIH Intramural Research Program; NIAID Division of AIDS; NIH Office of
AIDS Research; AIDS Vaccine Discovery grant from the Bill and Melinda
Gates Foundation [OPP1032325]; Delaney AIDS Research Enterprise
[AI096109]; NIAID [AI069994]; UCSF/Gladstone Institute of Virology &
Immunology CFAR [P30 AI027763]; NCI
FX We thank the study participants for their involvement in the study. We
thank S. Kosakovsky-Pond for help with phylogenetic analysis and C.
Petrovas for helpful discussions. D.C.D. and E.A.B. are funded by the
NIH Intramural Research Program. D.C.D. is also funded by the NIAID
Division of AIDS and the NIH Office of AIDS Research. Additional funding
came from AIDS Vaccine Discovery grant OPP1032325 from the Bill and
Melinda Gates Foundation (to R.A.K.), the Delaney AIDS Research
Enterprise (AI096109 to S.G.D.), NIAID K24 (AI069994 to S.G.D.), the
UCSF/Gladstone Institute of Virology & Immunology CFAR (P30 AI027763 to
S.G.D.), and federal funds from the NCI (to F.M. and S.H.H.).
NR 40
TC 9
Z9 9
U1 11
U2 12
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 AUG 11
PY 2016
VL 166
IS 4
BP 1004
EP 1015
DI 10.1016/j.cell.2016.06.039
PG 12
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA DU5NO
UT WOS:000382258700021
PM 27453467
ER
PT J
AU Zhao, HY
Fernandez, E
Dowd, KA
Speer, SD
Platt, DJ
Gorman, MJ
Govero, J
Nelson, CA
Pierson, TC
Diamond, MS
Fremont, DH
AF Zhao, Haiyan
Fernandez, Estefania
Dowd, Kimberly A.
Speer, Scott D.
Platt, Derek J.
Gorman, Matthew J.
Govero, Jennifer
Nelson, Christopher A.
Pierson, Theodore C.
Diamond, Michael S.
Fremont, Daved H.
TI Structural Basis of Zika Virus-Specific Antibody Protection
SO CELL
LA English
DT Article
ID WEST-NILE-VIRUS; CROSS-REACTIVE ANTIBODIES; TICK-BORNE ENCEPHALITIS;
DENGUE VIRUS; MONOCLONAL-ANTIBODY; ENVELOPE PROTEIN; DOMAIN-III;
FUSION-LOOP; NEUTRALIZATION; INFECTION
AB Zika virus (ZIKV) infection during pregnancy has emerged as a global public health problem because of its ability to cause severe congenital disease. Here, we developed six mouse monoclonal antibodies (mAbs) against ZIKV including four (ZV-48, ZV-54, ZV-64, and ZV-67) that were ZIKV specific and neutralized infection of African, Asian, and American strains to varying degrees. X-ray crystallographic and competition binding analyses of Fab fragments and scFvs defined three spatially distinct epitopes in DIII of the envelope protein corresponding to the lateral ridge (ZV-54 and ZV-67), C-C' loop (ZV-48 and ZV-64), and ABDE sheet (ZV-2) regions. In vivo passive transfer studies revealed protective activity of DIII-lateral ridge specific neutralizing mAbs in a mouse model of ZIKV infection. Our results suggest that DIII is targeted by multiple type-specific antibodies with distinct neutralizing activity, which provides a path for developing prophylactic antibodies for use in pregnancy or designing epitope-specific vaccines against ZIKV.
C1 [Zhao, Haiyan; Gorman, Matthew J.; Nelson, Christopher A.; Diamond, Michael S.] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA.
[Fernandez, Estefania; Platt, Derek J.; Govero, Jennifer; Diamond, Michael S.] Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA.
[Diamond, Michael S.; Fremont, Daved H.] Washington Univ, Sch Med, Dept Mol Microbiol, St Louis, MO 63110 USA.
[Fremont, Daved H.] Washington Univ, Sch Med, Dept Biochem & Mol Biophys, St Louis, MO 63110 USA.
[Nelson, Christopher A.; Diamond, Michael S.; Fremont, Daved H.] Washington Univ, Sch Med, Ctr Human Immunol & Immunotherapy Programs, St Louis, MO 63110 USA.
[Dowd, Kimberly A.; Speer, Scott D.; Pierson, Theodore C.] NIAID, Viral Pathogenesis Sect, NIH, Bethesda, MD 20892 USA.
RP Diamond, MS (reprint author), Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA.; Diamond, MS (reprint author), Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA.; Diamond, MS; Fremont, DH (reprint author), Washington Univ, Sch Med, Dept Mol Microbiol, St Louis, MO 63110 USA.; Fremont, DH (reprint author), Washington Univ, Sch Med, Dept Biochem & Mol Biophys, St Louis, MO 63110 USA.; Diamond, MS; Fremont, DH (reprint author), Washington Univ, Sch Med, Ctr Human Immunol & Immunotherapy Programs, St Louis, MO 63110 USA.
EM diamond@borcim.wustl.edu; fremont@wustl.edu
FU NIH [R01 AI073755, R01 AI104972, T32 AI007163]; NIAID
[HHSN272201400018C, HHSN272201200026C]; NIH Research Education Program
[R25 HG006687]; NIAID
FX This work was supported by NIH grants R01 AI073755 (to M.S.D. and D.H.F)
and R01 AI104972 (to M.S.D.), and NIAID contracts HHSN272201400018C (to
D.H.F. and M.S.D) and HHSN272201200026C (CSGID; to D.H.F.). E.F. and
D.J.P. were supported by an NIH Pre-doctoral training grant award (T32
AI007163) and the NIH Research Education Program (R25 HG006687),
respectively. K.A.D., S.D.S., and T.C.P. were funded by the intramural
program of NIAID. We acknowledge Jay Nix (MBC 4.2.2 beamline at ALS
Berkeley) for aid in remote data collection. M.S.D. consults for Inbios,
Visterra, Sanofi, and Takeda Pharmaceuticals, is on the Scientific
Advisory Boards of Moderna and OraGene, and has received research grants
from Moderna, Sanofi, and Visterra.
NR 53
TC 22
Z9 24
U1 23
U2 28
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 AUG 11
PY 2016
VL 166
IS 4
BP 1016
EP 1027
DI 10.1016/j.cell.2016.07.020
PG 12
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA DU5NO
UT WOS:000382258700022
PM 27475895
ER
PT J
AU Lee, SM
Wu, CK
Plieskatt, J
McAdams, DH
Miura, K
Ockenhouse, C
King, CR
AF Lee, Shwu-Maan
Wu, Chia-Kuei
Plieskatt, Jordan
McAdams, David H.
Miura, Kazutoyo
Ockenhouse, Chris
King, C. Richter
TI Assessment of Pfs25 expressed from multiple soluble expression platforms
for use as transmission-blocking vaccine candidates
SO MALARIA JOURNAL
LA English
DT Article
DE Malaria; Pfs25; Plasmodium falciparum; Transmission blocking vaccine;
Baculovirus; Pichia; Glycosylation; Recombinant protein
ID PLASMODIUM-FALCIPARUM; PICHIA-PASTORIS; LINKED GLYCOSYLATION; MALARIA
VACCINES; SEXUAL STAGE; PROTEIN; ANTIBODIES; PEPTIDES; SEQUENCE;
CRYSTALLIZATION
AB Background: Transmission-blocking vaccines (TBVs) have become a focus of strategies to control and eventually eliminate malaria as they target the entry of sexual stage into the Anopheles stephensi mosquito thereby preventing transmission, an essential component of the parasite life cycle. Such vaccines are envisioned as complements to vaccines that target human infection, such as RTS, S as well as drug treatment, and vector control strategies. A number of conserved proteins, including Pfs25, have been identified as promising TBV targets in research or early stage development. Pfs25 is a 25 kDa protein of Plasmodium falciparum expressed on the surface of zygotes and ookinetes. Its complex tertiary structure, including numerous cysteines, has led to difficulties in the expression of a recombinant protein that is homogeneous, with proper conformation, and free of glycosylation, a phenomenon not found in native parasite machinery.
Methods: While the expression and purification of Pfs25 in various systems, has been previously independently reported, here a parallel analysis of Pfs25 is presented to inform on the biochemical features of Pfs25 and their impact on functionality. Three scalable expression systems were used to express, purify, and evaluate Pfs25 both in vitro and in vivo, including the ability of each protein to produce functional antibodies through the standard membrane feeding assay.
Results: Through numerous attempts, soluble, monomeric Pfs25 derived from Escherichia coli was not achieved, while Pichia pastoris presented Pfs25 as an inhomogeneous product with glycosylation. In comparison, baculovirus produced a pure, monomeric protein free of glycosylation. The glycosylation present for Pichia produced Pfs25, showed no notable decrease in the ability to elicit transmission reducing antibodies in functional evaluation, while a reduced and alkylated Pfs25 (derived from plant and used as a control) was found to have significantly decreased transmission reducing activity, emphasizing the importance of ensuring correct disulfide stabilized conformation during vaccine design and production.
Conclusions: In this study, the biochemical features of Pfs25, produced from different expression systems, are described along with their impact on the ability of the protein to elicit functional antibodies. Pfs25 expressed using baculovirus and Pichia showed promise as candidates for vaccine development.
C1 [Lee, Shwu-Maan; Wu, Chia-Kuei; Plieskatt, Jordan; Ockenhouse, Chris; King, C. Richter] PATH Malaria Vaccine Initiat MVI, 455 Massachusetts Ave NW,Suite 1000, Washington, DC 20001 USA.
[McAdams, David H.] PATH, 2201 Westlake Ave,Suite 200, Seattle, WA 98121 USA.
[Miura, Kazutoyo] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA.
RP Lee, SM (reprint author), PATH Malaria Vaccine Initiat MVI, 455 Massachusetts Ave NW,Suite 1000, Washington, DC 20001 USA.
EM smlee@path.org
OI Lee, Shwu-Maan/0000-0003-0819-0569
FU Bill & Melinda Gates Foundation
FX The work presented here was funded in whole or part by a grant from the
Bill & Melinda Gates Foundation. The views expressed herein are solely
those of the authors and do not necessarily reflect the views of the
Foundation.
NR 35
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 1475-2875
J9 MALARIA J
JI Malar. J.
PD AUG 11
PY 2016
VL 15
AR 405
DI 10.1186/s12936-016-1464-6
PG 12
WC Infectious Diseases; Parasitology; Tropical Medicine
SC Infectious Diseases; Parasitology; Tropical Medicine
GA DT3CI
UT WOS:000381357700004
PM 27515826
ER
PT J
AU Bennett, WD
Ivins, S
Alexis, NE
Wu, JH
Bromberg, PA
Brar, SS
Travlos, G
London, SJ
AF Bennett, William D.
Ivins, Sally
Alexis, Neil E.
Wu, Jihong
Bromberg, Philip A.
Brar, Sukhdev S.
Travlos, Gregory
London, Stephanie J.
TI Effect of Obesity on Acute Ozone-Induced Changes in Airway Function,
Reactivity, and Inflammation in Adult Females
SO PLOS ONE
LA English
DT Article
ID BRONCHIAL RESPONSIVENESS; PULMONARY-FUNCTION; HUMAN-LUNG; RESPONSES;
ASTHMA; MICE; METHACHOLINE; DECREMENTS; MECHANISMS; CHALLENGE
AB We previously observed greater ozone-induced lung function decrements in obese than non-obese women. Animal models suggest that obesity enhances ozone-induced airway reactivity and inflammation. In a controlled exposure study, we compared the acute effect of randomized 0.4ppm ozone and air exposures (2 h with intermittent light exercise) in obese (N= 20) (30 < BMI < 40Kg/m2) vs. non- obese (N= 20) (BMI < 25Kg/m2) non- smoking 18-35 year old women. We measured spirometry and bronchial reactivity to inhaled methacholine (3h post-exposure). Inflammation and obesity markers were assessed in the blood (pre, 4h post, and 20h post exposures) and induced-sputum (4h post-exposures and on 24h preexposure training day, no exercise): measures of C reactive protein (CRP) (blood only), leptin (blood only), adiponectin, interleukins IL-6, IL-1b, and IL-8, and tumor necrosis factor alpha, and sputum cell differential cell counts. The pre-topost-exposure decrease in forced vital capacity after ozone (adjusted for the change after air exposure) was significantly greater in the obese group (12.5+/-7.5vs.8.0+/-5.8%,p < 0.05). Post ozone exposure, 6 obese and 6 non-obese subjects responded to methacholine at <= 10mg/ml ( the maximum dose); the degree of hyperresponsiveness was similar for the two groups. Both BMI groups showed similar and significant ozone-induced increases in sputum neutrophils. Plasma IL-6 was increased by exercise (4 hr post air exposure vs. pre) only in the obese but returned to pre-air exposure levels at 20hr post-exposure. Plasma IL-6 was significantly increased at 4hr post ozone exposure in both groups and returned to pre-exposure levels by 20h postexposure. These results confirm our previous findings of greater post-ozone spirometric decrements in obese young women. However, acute ozone-induced airway reactivity to methacholine and airway inflammation did not differ by obesity at the exposure and exercise levels used.
C1 [Bennett, William D.; Ivins, Sally; Alexis, Neil E.; Wu, Jihong; Bromberg, Philip A.] Univ N Carolina, Ctr Environm Med Asthma & Lung Biol, Chapel Hill, NC 27599 USA.
[Brar, Sukhdev S.; Travlos, Gregory; London, Stephanie J.] NIEHS, Div Intramural Res, NIH, Dept Hlth & Human Serv, POB 12233, Res Triangle Pk, NC 27709 USA.
RP Bennett, WD (reprint author), Univ N Carolina, Ctr Environm Med Asthma & Lung Biol, Chapel Hill, NC 27599 USA.
EM William_Bennett@med.unc.edu
OI London, Stephanie/0000-0003-4911-5290
FU National Institutes of Health, National Institute of Environmental
Health Sciences, USEPA [CR 83578501, CR 83346301]
FX This study was supported by the Intramural Research Program of the
National Institutes of Health, National Institute of Environmental
Health Sciences, USEPA cooperative agreement #CR 83578501, USEPA
cooperative agreement #CR 83346301.
NR 30
TC 1
Z9 1
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 AUG 11
PY 2016
VL 11
IS 8
AR e0160030
DI 10.1371/journal.pone.0160030
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DT3KY
UT WOS:000381381100023
PM 27513854
ER
PT J
AU La Porta, J
Matus-Nicodemos, R
Valentin-Acevedo, A
Covey, LR
AF La Porta, James
Matus-Nicodemos, Rodrigo
Valentin-Acevedo, Anibal
Covey, Lori R.
TI The RNA-Binding Protein, Polypyrimidine Tract-Binding Protein 1 (PTBP1)
Is a Key Regulator of CD4 T Cell Activation
SO PLOS ONE
LA English
DT Article
ID KINASE MESSENGER-RNA; GENE-EXPRESSION; CYCLIN D1; LIGAND EXPRESSION;
POSTTRANSCRIPTIONAL REGULATION; LYMPHOCYTE DEVELOPMENT;
GLUCOSE-METABOLISM; DEPENDENT MANNER; IN-VIVO; B-CELLS
AB We have previously shown that the RNA binding protein, polypyrimidine tract-binding protein (PTBP1) plays a critical role in regulating the expression of CD40L in activated CD4 T cells. This is achieved mechanistically through message stabilization at late times of activation as well as by altered distribution of CD40L mRNA within distinct cellular compartments. PTBP1 has been implicated in many different processes, however whether PTBP1 plays a broader role in CD4 T cell activation is not known. To examine this question, experiments were designed to introduce shRNA into primary human CD4 T cells to achieve decreased, but not complete ablation of PTBP1 expression. Analyses of shPTB-expressing CD4 T cells revealed multiple processes including cell proliferation, activation-induced cell death and expression of activation markers and cytokines that were regulated in part by PTBP1 expression. Although there was an overall decrease in the steady-state level of several activation genes, only IL-2 and CD40L appeared to be regulated by PTBP1 at the level of RNA decay suggesting that PTBP1 is critical at different regulatory steps of expression that is gene-specific. Importantly, even though the IL-2 protein levels were reduced in cells with lowered PTBP1, the steady-state level of IL-2 mRNA was significantly higher in these cells suggesting a block at the translational level. Evaluation of T cell activation in shPTBexpressing T cells revealed that PTBP1 was linked primarily to the activation of the PLC.1/ ERK1/2 and the NF-.B pathways. Overall, our results reveal the importance of this critical RNA binding protein in multiple steps of T cell activation.
C1 [La Porta, James; Matus-Nicodemos, Rodrigo; Valentin-Acevedo, Anibal; Covey, Lori R.] Rutgers State Univ, Dept Cell Biol & Neurosci, New Brunswick, NJ 08903 USA.
[Matus-Nicodemos, Rodrigo] NIAID, Immunol Lab, Vaccine Res Ctr, NIH, Bethesda, MD USA.
[Valentin-Acevedo, Anibal] Univ Puerto Rico, Dept Nat Sci, Aguadilla, PR USA.
RP Covey, LR (reprint author), Rutgers State Univ, Dept Cell Biol & Neurosci, New Brunswick, NJ 08903 USA.
EM covey@biology.rutgers.edu
FU National Institutes of Health/National Institute of Allergy and
Infectious Disease [R03 AI107811-01, PO1 AI-57596]
FX This work was funded in part by R03 AI107811-01 and PO1 AI-57596
(project #2) (National Institutes of Health/National Institute of
Allergy and Infectious Disease)(https://www.niaid.nih.gov) to LRC.
NR 76
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 AUG 11
PY 2016
VL 11
IS 8
AR e0158708
DI 10.1371/journal.pone.0158708
PG 21
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DT3KY
UT WOS:000381381100011
PM 27513449
ER
PT J
AU Louis, JM
Baber, JL
Ghirlando, R
Aniana, A
Bax, A
Roche, J
AF Louis, John M.
Baber, James L.
Ghirlando, Rodolfo
Aniana, Annie
Bax, Ad
Roche, Julien
TI Insights into the Conformation of the Membrane Proximal Regions Critical
to the Trimerization of the HIV-1 gp41 Ectodomain Bound to Dodecyl
Phosphocholine Micelles
SO PLOS ONE
LA English
DT Article
ID FUSION-ACTIVE CONFORMATION; ENVELOPE GLYCOPROTEIN; NEUTRALIZING
ANTIBODY; PROTEIN GP41; SEDIMENTATION-VELOCITY; ATOMIC-STRUCTURE;
MEDIATED FUSION; EXTERNAL REGION; VIRAL MEMBRANE; INTERMEDIATE
AB The transitioning of the ectodomain of gp41 from a pre-hairpin to a six-helix bundle conformation is a crucial aspect of virus-cell fusion. To gain insight into the intermediary steps of the fusion process we have studied the pH and dodecyl phosphocholine (DPC) micelle dependent trimer association of gp41 by systematic deletion analysis of an optimized construct termed 17-172 (residues 528 to 683 of Env) that spans the fusion peptide proximal region (FPPR) to the membrane proximal external region (MPER) of gp41, by sedimentation velocity and double electron-electron resonance (DEER) EPR spectroscopy. Trimerization at pH 7 requires the presence of both the FPPR and MPER regions. However, at pH 4, the protein completely dissociates to monomers. DEER measurements reveal a partial fraying of the C-terminal MPER residues in the 17-172 trimer while the other regions, including the FPPR, remain compact. In accordance, truncating nine C-terminal MPER residues (675-683) in the 17-172 construct does not shift the trimer-monomer equilibrium significantly. Thus, in the context of the gp41 ectodomain spanning residues 17-172, trimerization is clearly dependent on FPPR and MPER regions even when the terminal residues of MPER unravel. The antibody Z13e1, which spans both the 2F5 and 4E10 epitopes in MPER, binds to 17-172 with a K-d of 1 +/- 0.12 mu M. Accordingly, individual antibodies 2F5 and 4E10 also recognize the 17-172 trimer/DPC complex. We propose that binding of the C-terminal residues of MPER to the surface of the DPC micelles models a correct positioning of the trimeric transmembrane domain anchored in the viral membrane.
C1 [Louis, John M.; Baber, James L.; Aniana, Annie; Bax, Ad; Roche, Julien] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
[Ghirlando, Rodolfo] NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
[Roche, Julien] Iowa State Univ, Roy J Carver Dept Biochem Biophys & Mol Biol, Ames, IA USA.
RP Louis, JM; Roche, J (reprint author), NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.; Roche, J (reprint author), Iowa State Univ, Roy J Carver Dept Biochem Biophys & Mol Biol, Ames, IA USA.
EM johnl@niddk.nih.gov; julien.roche@nih.gov
FU Intramural Research Program of the NIDDK; National Institutes of Health;
NIH
FX This research was supported by the Intramural Research Program of the
NIDDK, National Institutes of Health and the Intramural AIDS-Targeted
Antiviral Program of the Office of the Director, NIH.
NR 55
TC 0
Z9 0
U1 11
U2 13
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 AUG 11
PY 2016
VL 11
IS 8
AR e0160597
DI 10.1371/journal.pone.0160597
PG 21
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DT3KY
UT WOS:000381381100047
PM 27513582
ER
PT J
AU Cobos, AJ
Nelson, CG
Jehn, M
Viboud, C
Chowell, G
AF Cobos, April J.
Nelson, Clinton G.
Jehn, Megan
Viboud, Cecile
Chowell, Gerardo
TI Mortality and transmissibility patterns of the 1957 influenza pandemic
in Maricopa County, Arizona
SO BMC INFECTIOUS DISEASES
LA English
DT Article
DE 1957 influenza; H2N2 virus; Asian influenza; Mathematical epidemiology;
Mortality rates; Transmissibility; Reproduction number; Maricopa County;
Arizona
ID EXCESS MORTALITY; REPRODUCTION NUMBER; EPIDEMIC INFLUENZA; WAVE; REGIONS
AB Background: While prior studies have quantified the mortality burden of the 1957 H2N2 influenza pandemic at broad geographic regions in the United States, little is known about the pandemic impact at a local level. Here we focus on analyzing the transmissibility and mortality burden of this pandemic in Arizona, a setting where the dry climate was promoted as reducing respiratory illness transmission yet tuberculosis prevalence was high.
Methods: Using archival death certificates from 1954 to 1961, we quantified the age-specific seasonal patterns, excess-mortality rates, and transmissibility patterns of the 1957 H2N2 pandemic in Maricopa County, Arizona. By applying cyclical Serfling linear regression models to weekly mortality rates, the excess-mortality rates due to respiratory and all-causes were estimated for each age group during the pandemic period. The reproduction number was quantified from weekly data using a simple growth rate method and assumed generation intervals of 3 and 4 days. Local newspaper articles published during 1957-1958 were also examined.
Results: Excess-mortality rates varied between waves, age groups, and causes of death, but overall remained low. From October 1959-June 1960, the most severe wave of the pandemic, the absolute excess-mortality rate based on respiratory deaths per 10,000 population was 16.59 in the elderly (>= 65 years). All other age groups exhibit very low excess-mortality and the typical U-shaped age-pattern was absent. However, the standardized mortality ratio was greatest (4.06) among children and young adolescents (5-14 years) from October 1957-March 1958, based on mortality rates of respiratory deaths. Transmissibility was greatest during the same 1957-1958 period, when the mean reproduction number was estimated at 1.08-1.11, assuming 3- or 4-day generation intervals with exponential or fixed distributions.
Conclusions: Maricopa County exhibited very low mortality impact associated with the 1957 influenza pandemic. Understanding the relatively low excess-mortality rates and transmissibility in Maricopa County during this historic pandemic may help public health officials prepare for and mitigate future outbreaks of influenza.
C1 [Cobos, April J.; Nelson, Clinton G.; Jehn, Megan; Chowell, Gerardo] Arizona State Univ, Sch Human Evolut & Social Change, Tempe, AZ 85281 USA.
[Cobos, April J.; Nelson, Clinton G.] Arizona State Univ, Sch Life Sci, Tempe, AZ USA.
[Cobos, April J.] Arizona State Univ, Barrett Honors Coll, Tempe, AZ USA.
[Viboud, Cecile; Chowell, Gerardo] NIH, Div Int Epidemiol & Populat Studies, Fogarty Int Ctr, Bldg 10, Bethesda, MD 20892 USA.
[Chowell, Gerardo] Georgia State Univ, Sch Publ Hlth, Atlanta, GA 30303 USA.
RP Chowell, G (reprint author), Arizona State Univ, Sch Human Evolut & Social Change, Tempe, AZ 85281 USA.; Chowell, G (reprint author), NIH, Div Int Epidemiol & Populat Studies, Fogarty Int Ctr, Bldg 10, Bethesda, MD 20892 USA.
EM gchowell@gsu.edu
FU Multinational Influenza Seasonal Mortality Study (MISMS)
FX We would like to thank the undergraduate students who assisted in
collecting the raw data. April Cobos would like to thank Melinda Jenner
for advice on mathematical modeling tools. This work was partially
supported by the Multinational Influenza Seasonal Mortality Study
(MISMS), an on-going international collaborative effort to understand
influenza epidemiological and evolutionary patterns, led by the Fogarty
International Center, National Institutes of Health
(http://www.origem.info/misms/index.php).
NR 44
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 1471-2334
J9 BMC INFECT DIS
JI BMC Infect. Dis.
PD AUG 11
PY 2016
VL 16
AR 405
DI 10.1186/s12879-016-1716-7
PG 14
WC Infectious Diseases
SC Infectious Diseases
GA DT2YP
UT WOS:000381348000006
PM 27516082
ER
PT J
AU Stavreva, DA
Varticovski, L
Levkova, L
George, AA
Davis, L
Pegoraro, G
Blazer, V
Iwanowicz, L
Hager, GL
AF Stavreva, Diana A.
Varticovski, Lyuba
Levkova, Ludmila
George, Anuja A.
Davis, Luke
Pegoraro, Gianluca
Blazer, Vicki
Iwanowicz, Luke
Hager, Gordon L.
TI Novel cell-based assay for detection of thyroid receptor
beta-interacting environmental contaminants
SO TOXICOLOGY
LA English
DT Article
DE EDCs; TR beta; High-throughput cell assay; BPA; TBBPA
ID ENDOCRINE-DISRUPTING CHEMICALS; GREEN FLUORESCENT PROTEIN; REPORTER GENE
ASSAY; IN-VITRO; HORMONE DISRUPTION; REPRODUCTIVE HEALTH; NUCLEAR
RECEPTORS; LIVING CELLS; BISPHENOL-A; TRANSLOCATION
AB Even though the presence of endocrine disrupting chemicals (EDCs) with thyroid hormone (TH)-like activities in the environment is a major health concern, the methods for their efficient detection and monitoring are still limited. Here we describe a novel cell assay, based on the translocation of a green fluorescent protein (GFP) tagged chimeric molecule of glucocorticoid receptor (GR) and the thyroid receptor beta (TR beta) from the cytoplasm to the nucleus in the presence of TR ligands. Unlike the constitutively nuclear TR beta, this GFP-GR-TR beta chimera is cytoplasmic in the absence of hormone while translocating to the nucleus in a time- and concentration-dependent manner upon stimulation with triiodothyronine (T3) and thyroid hormone analogue, TRIAC, while the reverse triiodothyronine (3,3',5'-triiodothyronine, or rT3) was inactive. Moreover, GFP-GR-TR beta chimera does not show any cross reactivity with the GR-activating hormones, thus providing a clean system for the screening of TR beta interacting EDCs. Using this assay, we demonstrated that Bisphenol A (BPA) and 3,3',5,5'-Tetrabromobisphenol (TBBPA) induced GFP-GR-TR beta translocation at micro molar concentrations. We screened over 100 concentrated water samples from different geographic locations in the United States and detected a low, but reproducible contamination in 53% of the samples. This system provides a novel high throughput approach for screening for endocrine disrupting chemicals (EDCs) interacting with TR beta. Published by Elsevier Ireland Ltd.
C1 [Stavreva, Diana A.; Varticovski, Lyuba; George, Anuja A.; Davis, Luke; Pegoraro, Gianluca; Hager, Gordon L.] NCI, Lab Receptor Biol & Gene Express, NIH, Bldg 41,B602,41 Lib Dr, Bethesda, MD 20892 USA.
[Levkova, Ludmila] Univ Utah, Dept Phys & Astron, Phys & Astron, Salt Lake City, UT USA.
[Blazer, Vicki; Iwanowicz, Luke] US Geol Survey, Leetown Sci Ctr, Natl Fish Hlth Res Lab, 11649 Leetown Rd, Kearneysville, WV 25430 USA.
[George, Anuja A.] Rutgers Robert Wood Johnson Med Sch, Dept Pharmacol, 675 Hoes Lane, Piscataway, NJ 08854 USA.
[Davis, Luke] Tulane Univ, 6823 St Charles Ave, New Orleans, LA 70118 USA.
RP Stavreva, DA; Hager, GL (reprint author), NCI, Lab Receptor Biol & Gene Express, NIH, Bldg 41,B602,41 Lib Dr, Bethesda, MD 20892 USA.
EM stavrevd@mail.nih.gov; hagerg@exchange.nih.gov
RI George, Anuja/C-5963-2017;
OI George, Anuja/0000-0003-2643-6307; Iwanowicz, Luke/0000-0002-1197-6178
FU Intramural Research Program of the NIH, Center for Cancer Research,
National Cancer Institute, National Institutes of Health
[HHSN261200800001E]; NCI High Throughput Facility
FX This study has been funded in whole or in part with Federal funds from
the Intramural Research Program of the NIH, Center for Cancer Research,
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. The use of trade, firm, or product names is for
descriptive purposes only and does not imply endorsement by the U.S.
Government. We acknowledge the support of the NCI High Throughput
Facility. We also acknowledge the assistance of Tatiana Karpova, LRBGE
Fluorescence Imaging Facility.
NR 46
TC 0
Z9 0
U1 4
U2 4
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 AUG 10
PY 2016
VL 368
BP 69
EP 79
DI 10.1016/j.tox.2016.08.012
PG 11
WC Pharmacology & Pharmacy; Toxicology
SC Pharmacology & Pharmacy; Toxicology
GA EB2NO
UT WOS:000387199300008
PM 27528272
ER
PT J
AU Shenai, S
Ronacher, K
Malherbe, S
Stanley, K
Kriel, M
Winter, J
Peppard, T
Barry, CE
Wang, J
Dodd, LE
Via, LE
Barry, CE
Walzl, G
Alland, D
AF Shenai, Shubhada
Ronacher, Katharina
Malherbe, Stefanus
Stanley, Kim
Kriel, Magdalena
Winter, Jill
Peppard, Thomas
Barry, Charles E.
Wang, Jing
Dodd, Lori E.
Via, Laura E.
Barry, Clifton E., III
Walzl, Gerhard
Alland, David
TI Bacterial Loads Measured by the Xpert MTB/RIF Assay as Markers of
Culture Conversion and Bacteriological Cure in Pulmonary TB
SO PLOS ONE
LA English
DT Article
ID TUBERCULOSIS TREATMENT; MYCOBACTERIUM-TUBERCULOSIS; RIFAMPIN RESISTANCE;
TREATMENT RESPONSE; CLINICAL-TRIALS; TIME; BIOMARKERS; RELAPSE; LIQUID;
RISK
AB Introduction
Biomarkers are needed to monitor tuberculosis (TB) treatment and predict treatment outcomes. We evaluated the Xpert MTB/RIF (Xpert) assay as a biomarker for TB treatment during and at the end of the 24 weeks therapy.
Methods
Sputum from 108 HIV-negative, culture-positive pulmonary TB patients was analyzed using Xpert at time points before and during anti-TB therapy. Results were compared against culture. Direct Xpert cycle-threshold (Ct), a change in the Ct (delta Ct), or a novel "percent closing of baseline Ct deficit" (percent closing) were evaluated as classifiers of same-day and end-of-treatment culture and therapeutic outcomes.
Results
Xpert was positive in 29/95 (30.5%) of subjects at week 24; and positive one year after treatment in 8/64 (12.5%) successfully-treated patients who remained free of tuberculosis. We identified a relationship between initial bacterial load measured by baseline Xpert Ct and time to culture conversion (hazard ratio 1.06, p = 0.0023), and to the likelihood of being among the 8 treatment failures at week 24 (AUC = 72.8%). Xpert Ct was even more strongly associated with culture conversion on the day the test was performed with AUCs 96.7%, 99.2%, 86.0% and 90.2%, at Day 7, Week 4, 8 and 24, respectively. Compared to baseline Ct measures alone, a combined measure of baseline Ct plus either Delta Ct or percent closing improved the classification of treatment failure status to a 75% sensitivity and 88.9% specificity.
Conclusions
Genome loads measured by Xpert provide a potentially-useful biomarker for classifying same day culture status and predicting response to therapy.
C1 [Shenai, Shubhada; Alland, David] Rutgers Biomed & Hlth Sci, Rutgers New Jersey Med Sch, Div Infect Dis, 185 South Orange Ave, Newark, NJ 07103 USA.
[Ronacher, Katharina; Malherbe, Stefanus; Stanley, Kim; Kriel, Magdalena; Walzl, Gerhard] Univ Stellenbosch, Fac Med & Hlth Sci, DST NRF Ctr Excellence Biomed TB Res, Cape Town, South Africa.
[Ronacher, Katharina; Malherbe, Stefanus; Stanley, Kim; Kriel, Magdalena; Walzl, Gerhard] Univ Stellenbosch, Fac Med & Hlth Sci, MRC Ctr TB Res, Div Mol Biol & Human Genet,Dept Biomed Sci, Cape Town, South Africa.
[Winter, Jill] Catalysis Fdn Hlth, Emeryville, CA 94608 USA.
[Peppard, Thomas] Certara LP, Greater Detroit Area, Detroit, MI 48226 USA.
[Barry, Charles E.] Brown Univ, Providence, RI 02912 USA.
[Wang, Jing] Leidos Biomed Res Inc, Clin Monitoring Res Program, Clin Res Directorate, NCI Campus Frederick, Frederick, MD USA.
[Dodd, Lori E.] NIAID, Biostat Res Branch, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Via, Laura E.; Barry, Clifton E., III] NIAID, TB Res Sect, Lab Clin Infect Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Via, Laura E.; Barry, Clifton E., III] Univ Cape Town, Fac Hlth Sci, Inst Infect Dis & Mol Med, ZA-7701 Rondebosch, South Africa.
[Via, Laura E.; Barry, Clifton E., III] Univ Cape Town, Fac Hlth Sci, Dept Clin Lab Sci, ZA-7701 Rondebosch, South Africa.
RP Alland, D (reprint author), Rutgers Biomed & Hlth Sci, Rutgers New Jersey Med Sch, Div Infect Dis, 185 South Orange Ave, Newark, NJ 07103 USA.
EM allandda@njms.rutgers.edu
RI Ronacher, Katharina/N-9603-2016
OI Ronacher, Katharina/0000-0002-6371-1462
FU Catalysis Foundation for Health; Intramural Research Program of the
NIAID, National Institutes of Health; Intramural Research program of the
NIAID, NIH [OPP51919]; National Cancer Institute, National Institutes of
Health [HHSN261200800001E]
FX This work was supported the Catalysis Foundation for Health and by the
Intramural Research Program of the NIAID, National Institutes of Health
(CEB), by the Intramural Research program of the NIAID, NIH (CEB) Grant
No - OPP51919, and with federal funds from the National Cancer
Institute, National Institutes of Health, under Contract No.
HHSN261200800001E. The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.; We thank all patients for participation in this study and
the clinic and Laboratory staff from the Stellenbosch University, Cape
Town, South Africa for technical assistance. This work was supported by
the Catalysis Foundation for Health and by the Intramural Research
Program of the NIAID, National Institutes of Health (CEB), by the
Intramural Research program of the NIAID, NIH (CEB) Grant No-OPP51919,
and with federal funds from the National Cancer Institute, National
Institutes of Health, under Contract No. HHSN261200800001E. The funders
had no role in study design, data collection and analysis, decision to
publish, or preparation of the manuscript.
NR 25
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 AUG 10
PY 2016
VL 11
IS 8
AR e0160062
DI 10.1371/journal.pone.0160062
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DT3KR
UT WOS:000381380400020
PM 27508390
ER
PT J
AU Shin, SY
Kim, S
Wilbur, WJ
Kwon, D
AF Shin, Soo-Yong
Kim, Sun
Wilbur, W. John
Kwon, Dongseop
TI BioC viewer: a web-based tool for displaying and merging annotations in
BioC
SO DATABASE-THE JOURNAL OF BIOLOGICAL DATABASES AND CURATION
LA English
DT Article
AB BioC is an XML-based format designed to provide interoperability for text mining tools and manual curation results. A challenge of BioC as a standard format is to align annotations from multiple systems. Ideally, this should not be a major problem if users follow guidelines given by BioC key files. Nevertheless, the misalignment between text and annotations happens quite often because different systems tend to use different software development environments, e.g. ASCII vs. Unicode. We first implemented the BioC Viewer to assist BioGRID curators as a part of the BioCreative V BioC track (Collaborative Biocurator Assistant Task). For the BioC track, the BioC Viewer helped curate protein-protein interaction and genetic interaction pairs appearing in full-text articles. Here, we describe the BioC Viewer itself as well as improvements made to the BioC Viewer since the BioCreative V Workshop to address the misalignment issue of BioC annotations. While uploading BioC files, a BioC merge process is offered when there are files from the same full-text article. If there is a mismatch between an annotated offset and text, the BioC Viewer adjusts the offset to correctly align with the text. The BioC Viewer has a user-friendly interface, where most operations can be performed within a few mouse clicks. The feedback from BioGRID curators has been positive for the web interface, particularly for its usability and learnability.
C1 [Shin, Soo-Yong] Asan Med Ctr, Dept Biomed Informat, Seoul 05505, South Korea.
[Kim, Sun; Wilbur, W. John] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
[Kwon, Dongseop] Myongji Univ, Deptartment Comp Engn, Yongin 17058, Gyeonggi Do, South Korea.
RP Kwon, D (reprint author), Myongji Univ, Deptartment Comp Engn, Yongin 17058, Gyeonggi Do, South Korea.
EM dongseop@mju.ac.kr
FU Myongji University; Genome Program for Fostering New Post-Genome
Industry of National Research Foundation (NRF) - Korean government
(MSIP) [NRF-2014M3C9A3064706]; Asan Institute for Life Sciences
[2013-7205]; Intramural Research Program of National Institutes of
Health, National Library of Medicine
FX The 2007 Research Fund of Myongji University to D.K.; The Genome Program
for Fostering New Post-Genome Industry of the National Research
Foundation (NRF) funded by the Korean government (MSIP)
(NRF-2014M3C9A3064706) to D.K.; The grant (2013-7205) from the Asan
Institute for Life Sciences to S.Y.S.; Intramural Research Program of
the National Institutes of Health, National Library of Medicine to S.K.
and W.J.W.
NR 15
TC 1
Z9 1
U1 0
U2 0
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1758-0463
J9 DATABASE-OXFORD
JI Database
PD AUG 10
PY 2016
AR baw106
DI 10.1093/database/baw106
PG 7
WC Mathematical & Computational Biology
SC Mathematical & Computational Biology
GA DT5KI
UT WOS:000381521700001
ER
PT J
AU Schmidt, MK
Hogervorst, F
van Hien, R
Cornelissen, S
Broeks, A
Adank, MA
Meijers, H
Waisfisz, Q
Hollestelle, A
Schutte, M
van den Ouweland, A
Hooning, M
Andrulis, IL
Anton-Culver, H
Antonenkova, NN
Antoniou, AC
Arndt, V
Bermisheva, M
Bogdanova, NV
Bolla, MK
Brauch, H
Brenner, H
Bruning, T
Burwinkel, B
Chang-Claude, J
Chenevix-Trench, G
Couch, FJ
Cox, A
Cross, SS
Czene, K
Dunning, AM
Fasching, PA
Figueroa, J
Fletcher, O
Flyger, H
Galle, E
Garcia-Closas, M
Giles, GG
Haeberle, L
Hall, P
Hillemanns, P
Hopper, JL
Jakubowska, A
John, EM
Jones, M
Khusnutdinova, E
Knight, JA
Kosma, VM
Kristensen, V
Lee, A
Lindblom, A
Lubinski, J
Mannermaa, A
Margolin, S
Meindl, A
Milne, RL
Muranen, TA
Newcomb, PA
Offit, K
Park-Simon, TW
Peto, J
Pharoah, PDP
Robson, M
Rudolph, A
Sawyer, EJ
Schmutzler, RK
Seynaeve, C
Soens, J
Southey, MC
Spurdle, AB
Surowy, H
Swerdlow, A
Tollenaar, RAEM
Tomlinson, I
Trentham-Dietz, A
Vachon, C
Wang, Q
Whittemore, AS
Ziogas, A
van der Kolk, L
Nevanlinna, H
Dork, T
Bojesen, S
Easton, DF
AF Schmidt, Marjanka K.
Hogervorst, Frans
van Hien, Richard
Cornelissen, Sten
Broeks, Annegien
Adank, Muriel A.
Meijers, Hanne
Waisfisz, Quinten
Hollestelle, Antoinette
Schutte, Mieke
van den Ouweland, Ans
Hooning, Maartje
Andrulis, Irene L.
Anton-Culver, Hoda
Antonenkova, Natalia N.
Antoniou, Antonis C.
Arndt, Volker
Bermisheva, Marina
Bogdanova, Natalia V.
Bolla, Manjeet K.
Brauch, Hiltrud
Brenner, Hermann
Bruning, Thomas
Burwinkel, Barbara
Chang-Claude, Jenny
Chenevix-Trench, Georgia
Couch, Fergus J.
Cox, Angela
Cross, Simon S.
Czene, Kamila
Dunning, Alison M.
Fasching, Peter A.
Figueroa, Jonine
Fletcher, Olivia
Flyger, Henrik
Galle, Eva
Garcia-Closas, Montserrat
Giles, Graham G.
Haeberle, Lothar
Hall, Per
Hillemanns, Peter
Hopper, John L.
Jakubowska, Anna
John, Esther M.
Jones, Michael
Khusnutdinova, Elza
Knight, Julia A.
Kosma, Veli-Matti
Kristensen, Vessela
Lee, Andrew
Lindblom, Annika
Lubinski, Jan
Mannermaa, Arto
Margolin, Sara
Meindl, Alfons
Milne, Roger L.
Muranen, Taru A.
Newcomb, Polly A.
Offit, Kenneth
Park-Simon, Tjoung-Won
Peto, Julian
Pharoah, Paul D. P.
Robson, Mark
Rudolph, Anja
Sawyer, Elinor J.
Schmutzler, Rita K.
Seynaeve, Caroline
Soens, Julie
Southey, Melissa C.
Spurdle, Amanda B.
Surowy, Harald
Swerdlow, Anthony
Tollenaar, Rob A. E. M.
Tomlinson, Ian
Trentham-Dietz, Amy
Vachon, Celine
Wang, Qin
Whittemore, Alice S.
Ziogas, Argyrios
van der Kolk, Lizet
Nevanlinna, Heli
Doerk, Thilo
Bojesen, Stig
Easton, Douglas F.
TI Age- and Tumor Subtype Specific Breast Cancer Risk Estimates for
CHEK2*1100delC Carriers
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID WOMEN; MUTATION; 1100DELC; CHEK2; SUSCEPTIBILITY; PREDICTION; CHK2;
KINASES; SURGERY; BRCA1
AB Purpose
CHEK2*1100delC is a well-established breast cancer risk variant that is most prevalent in European populations; however, there are limited data on risk of breast cancer by age and tumor subtype, which limits its usefulness in breast cancer risk prediction. We aimed to generate tumor subtype and age-specific risk estimates by using data from the Breast Cancer Association Consortium, including 44,777 patients with breast cancer and 42,997 controls from 33 studies genotyped for CHEK2*1100delC.
Patients and Methods
CHEK71100delC genotyping was mostly done by a custom Taqman assay. Breast cancer odds ratios (ORs) for CHEK71100delC carriers versus noncarriers were estimated by using logistic regression and adjusted for study (categorical) and age. Main analyses included patients with invasive breast cancer from population- and hospital-based studies.
Results
Proportions of heterozygous CHEK2*1100delC carriers in controls, in patients with breast cancer from population- and hospital-based studies, and in patients with breast cancer from familial- and clinical genetics center based studies were 0.5%, 1.3%, and 3.0%, respectively. The estimated OR for invasive breast cancer was 2.26 (95%CI, 1.90 to 2.69; P = 2.3 x 10(-20)). The OR was higher for estrogen receptor (ER) positive disease (2.55 [95%CI, 2.10 to 3.10; P = 4.9 x 10(-21)]) than it was for ER-negative disease (1.32 [95%CI, 0.93 to 1.88; P = .12]; P interaction = 9.9 x 10(-4)). The OR significantly declined with attained age for breast cancer overall (P = .001) and for ER-positive tumors (P = .001). Estimated cumulative risks for development of ER-positive and ER-negative tumors by age 80 in CHEK2*1100delC carriers were 20% and 3%, respectively, compared with 9% and 2%, respectively, in the general population of the United Kingdom.
Conclusion
These CHEK2*1100delC breast cancer risk estimates provide a basis for incorporating CHEK2*1100delC into breast cancer risk prediction models and into guidelines for intensified screening and follow-up. J Clin Oncol 34:2750-2760. (C) 2016 by American Society of Clinical Oncology
C1 [Schmidt, Marjanka K.; Hogervorst, Frans; van Hien, Richard; Cornelissen, Sten; Broeks, Annegien; van der Kolk, Lizet] Antoni van Leeuwenhoek Hosp, Netherlands Canc Inst, Amsterdam, Netherlands.
[Adank, Muriel A.; Meijers, Hanne; Waisfisz, Quinten] Vrije Univ Amsterdam, Med Ctr, Amsterdam, Netherlands.
[Hollestelle, Antoinette; Schutte, Mieke; Hooning, Maartje; Seynaeve, Caroline] Erasmus MC, Inst Canc, Rotterdam, Netherlands.
[van den Ouweland, Ans] Erasmus MC, Rotterdam, Netherlands.
[Tollenaar, Rob A. E. M.] Leiden Univ, Med Ctr, Leiden, Netherlands.
[Andrulis, Irene L.; Knight, Julia A.] Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, New York, NY USA.
[Andrulis, Irene L.; Knight, Julia A.] Univ Toronto, Toronto, ON, Canada.
[Anton-Culver, Hoda; Ziogas, Argyrios] Univ Calif Irvine, Irvine, CA USA.
[Fasching, Peter A.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA.
[John, Esther M.] Canc Prevent Inst Calif, Fremont, CA USA.
[John, Esther M.; Whittemore, Alice S.] Stanford Univ, Sch Med, Stanford, CA 94305 USA.
[Antonenkova, Natalia N.] NN Alexandrov Res Inst Oncol & Med Radiol, Minsk, Byelarus.
[Antoniou, Antonis C.; Bolla, Manjeet K.; Dunning, Alison M.; Lee, Andrew; Pharoah, Paul D. P.; Wang, Qin; Easton, Douglas F.] Univ Cambridge, Cambridge CB2 1TN, England.
[Cox, Angela; Cross, Simon S.] Univ Sheffield, Sheffield, S Yorkshire, England.
[Fletcher, Olivia; Jones, Michael; Swerdlow, Anthony] Kings Coll London, Inst Canc Res, London WC2R 2LS, England.
[Peto, Julian] Kings Coll London, London Sch Hyg & Trop Med, London WC2R 2LS, England.
[Sawyer, Elinor J.] Kings Coll London, London WC2R 2LS, England.
[Figueroa, Jonine] Univ Edinburgh, Sch Med, Edinburgh, Midlothian, Scotland.
[Tomlinson, Ian] Univ Oxford, Oxford, England.
[Arndt, Volker; Brauch, Hiltrud; Brenner, Hermann; Burwinkel, Barbara; Chang-Claude, Jenny; Rudolph, Anja; Surowy, Harald] German Canc Res Ctr, Heidelberg, Germany.
[Burwinkel, Barbara; Surowy, Harald] Heidelberg Univ, Bergheimer Str 58, D-69115 Heidelberg, Germany.
[Bogdanova, Natalia V.; Hillemanns, Peter; Park-Simon, Tjoung-Won; Doerk, Thilo] Hannover Med Sch, Hannover, Germany.
[Brauch, Hiltrud] Dr Margarete Fischer Bosch Inst Clin Pharmacol, Stuttgart, Germany.
[Brauch, Hiltrud] Univ Tubingen, Tubingen, Germany.
[Bruning, Thomas] Inst Ruhr Univ Bochum, German Social Accid Insurance, Bochum, Germany.
[Chang-Claude, Jenny] Univ Med Ctr Hamburg Eppendorf, Hamburg, Germany.
Friedrich Alexander Univ Erlangen Nuremberg, Comprehens Canc Ctr Erlangen EMN, Univ Hosp Erlangen, Erlangen, Germany.
[Meindl, Alfons] Tech Univ Munich, Munich, Germany.
[Schmutzler, Rita K.] Univ Hosp Cologne, Cologne, Germany.
[Schmutzler, Rita K.] Univ Cologne, Cologne, Germany.
[Bermisheva, Marina] Russian Acad Sci, Ufa Sci Ctr, Moscow, Russia.
[Khusnutdinova, Elza] Bashkir State Univ, Ufa, Russia.
[Chenevix-Trench, Georgia; Spurdle, Amanda B.] QIMR Berghofer Med Res Inst, Brisbane, Qld, Australia.
[Giles, Graham G.; Milne, Roger L.] Canc Council Victoria, Melbourne, Vic, Australia.
[Giles, Graham G.; Hopper, John L.; Milne, Roger L.; Southey, Melissa C.] Univ Melbourne, Melbourne, Vic, Australia.
[Couch, Fergus J.; Vachon, Celine] Mayo Clin, Rochester, MN USA.
[Czene, Kamila; Hall, Per; Lindblom, Annika; Margolin, Sara] Karolinska Inst, Stockholm, Sweden.
[Figueroa, Jonine; Garcia-Closas, Montserrat] NCI, Rockville, MD USA.
[Flyger, Henrik; Bojesen, Stig] Copenhagen Univ Hosp, Herlev & Gentofte Hosp, Herlev, Denmark.
[Bojesen, Stig] Univ Copenhagen, Copenhagen, Denmark.
[Galle, Eva] Univ Leuven, Leuven, Belgium.
[Galle, Eva] Vesalius Res Ctr, Leuven, Belgium.
[Soens, Julie] Univ Hosp Gasthuisberg, Leuven, Belgium.
[Jakubowska, Anna; Lubinski, Jan] Pomeranian Med Univ, Szczecin, Poland.
[Kosma, Veli-Matti; Mannermaa, Arto] Univ Eastern Finland, Joensuu, Finland.
[Kosma, Veli-Matti; Mannermaa, Arto] Kuopio Univ Hosp, Kuopio, Finland.
[Muranen, Taru A.; Nevanlinna, Heli] Univ Helsinki, Helsinki, Finland.
[Kristensen, Vessela] Radiumhosp, Oslo Univ Hosp, Oslo, Norway.
[Kristensen, Vessela] Univ Oslo, Oslo, Norway.
[Newcomb, Polly A.; Trentham-Dietz, Amy] Univ Wisconsin, Madison, WI USA.
[Newcomb, Polly A.] Fred Hutchinson Canc Res Ctr, 1124 Columbia St, Seattle, WA 98104 USA.
[Offit, Kenneth; Robson, Mark] Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA.
RP Schmidt, MK (reprint author), Antoni van Leeuwenhoek Hosp, Netherlands Canc Inst, Div Mol Pathol, Plesmanlaan 121, NL-1066 CX Amsterdam, Netherlands.; Schmidt, MK (reprint author), Antoni van Leeuwenhoek Hosp, Netherlands Canc Inst, Div Psychosocial Res & Epidemiol, Plesmanlaan 121, NL-1066 CX Amsterdam, Netherlands.
EM mk.schmidt@nki.nl
RI Knight, Julia/A-6843-2012; Bruning, Thomas/G-8120-2015; Dork,
Thilo/J-8620-2012; Khusnutdinova, Elza/A-4810-2013; Brenner,
Hermann/B-4627-2017;
OI Bruning, Thomas/0000-0001-9560-5464; Brenner,
Hermann/0000-0002-6129-1572; Muranen, Taru/0000-0002-5895-1808; Dunning,
Alison Margaret/0000-0001-6651-7166
FU Cancer Research UK [10118, 10119, 10124, 11174]; NCI NIH HHS [P50
CA116201, K07 CA092044, R01 CA047147, R01 CA047305, R01 CA058860, R01
CA069664, R01 CA116167, R01 CA176785, R01 CA192393, U01 CA058860, U01
CA116167, UM1 CA164920]
NR 28
TC 4
Z9 4
U1 8
U2 10
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 AUG 10
PY 2016
VL 34
IS 23
BP 2750
EP +
DI 10.1200/JCO.2016.66.5844
PG 25
WC Oncology
SC Oncology
GA DU8MF
UT WOS:000382467000012
PM 27269948
ER
PT J
AU Lopatina, N
McDannald, MA
Styer, CV
Peterson, JF
Sadacca, BF
Cheer, JF
Schoenbaum, G
AF Lopatina, Nina
McDannald, Michael A.
Styer, Clay V.
Peterson, Jacob F.
Sadacca, Brian F.
Cheer, Joseph F.
Schoenbaum, Geoffrey
TI Medial Orbitofrontal Neurons Preferentially Signal Cues Predicting
Changes in Reward during Unblocking
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
DE orbitofrontal; Pavlovian; rat; single unit
ID VENTROMEDIAL PREFRONTAL CORTEX; DECISION-MAKING; ECONOMIC VALUE;
REINFORCER DEVALUATION; BASOLATERAL AMYGDALA; GOAL VALUES;
REPRESENTATION; BRAIN
AB The orbitofrontal cortex (OFC) has been broadly implicated in the ability to use the current value of expected outcomes to guide behavior. Although value correlates have been prominently reported in lateral OFC, they are more often associated with more medial areas. Further, recent studies in primates have suggested a dissociation in which the lateral OFC is involved in credit assignment and representation of reward identity and more medial areas are critical to representing value. Previously, we used unblocking to test more specifically what information about outcomes is represented by OFC neurons in rats; consistent with the proposed dichotomy between the lateral and medial OFC, we found relatively little linear value coding in the lateral OFC (Lopatina et al., 2015). Here we have repeated this experiment, recording in the medial OFC, to test whether such value signals might be found there. Neurons were recorded in an unblocking task as rats learned about cues that signaled either more, less, or the same amount of reward. We found that medial OFC neurons acquired responses to these cues; however, these responses did not signal different reward values across cues. Surprisingly, we found that cells developed responses to cues predicting a change, particularly a decrease, in reward value. This is consistent with a special role for medial OFC in representing current value to support devaluation/revaluation sensitive changes in behavior.
C1 [Lopatina, Nina; Styer, Clay V.; Peterson, Jacob F.; Sadacca, Brian F.; Schoenbaum, Geoffrey] Natl Inst Drug Abuse, Intramural Res Program, Baltimore, MD 21224 USA.
[McDannald, Michael A.] Boston Coll, Dept Psychol, Chestnut Hill, MA 02467 USA.
[Lopatina, Nina] Univ Maryland, Sch Med, Program Neurosci, Baltimore, MD 21201 USA.
[Cheer, Joseph F.; Schoenbaum, Geoffrey] Univ Maryland, Sch Med, Dept Anat & Neurobiol, Baltimore, MD 21201 USA.
[Schoenbaum, Geoffrey] Johns Hopkins Univ, Dept Neurosci, Baltimore, MD 21205 USA.
RP Schoenbaum, G (reprint author), Behav Neurophysiol Res Sect, Cellular Neurobiol Res Branch, 251 Bayview Blvd,Suite 200,Bldg BRC,Room 06A705, Baltimore, MD 21224 USA.
EM geoffrey.schoenbaum@nih.gov
OI Sadacca, Brian/0000-0003-1425-6077
FU Intramural Research Program at the National Institute on Drug Abuse
FX This work was supported by the Intramural Research Program at the
National Institute on Drug Abuse. The opinions expressed in this article
are the authors' own and do not reflect the view of the National
Institutes of Health/Department of Health and Human Services.
NR 26
TC 0
Z9 0
U1 5
U2 5
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 AUG 10
PY 2016
VL 36
IS 32
BP 8416
EP 8424
DI 10.1523/JNEUROSCI.1101-16.2016
PG 9
WC Neurosciences
SC Neurosciences & Neurology
GA DU6GQ
UT WOS:000382312700012
PM 27511013
ER
PT J
AU Tran, TM
Jones, MB
Ongoiba, A
Bijker, EM
Schats, R
Venepally, P
Skinner, J
Doumbo, S
Quinten, E
Visser, LG
Whalen, E
Presnell, S
O'Connell, EM
Kayentao, K
Doumbo, OK
Chaussabel, D
Lorenzi, H
Nutman, TB
Ottenhoff, THM
Haks, MC
Traore, B
Kirkness, EF
Sauerwein, RW
Crompton, PD
AF Tran, Tuan M.
Jones, Marcus B.
Ongoiba, Aissata
Bijker, Else M.
Schats, Remko
Venepally, Pratap
Skinner, Jeff
Doumbo, Safiatou
Quinten, Edwin
Visser, Leo G.
Whalen, Elizabeth
Presnell, Scott
O'Connell, Elise M.
Kayentao, Kassoum
Doumbo, Ogobara K.
Chaussabel, Damien
Lorenzi, Hernan
Nutman, Thomas B.
Ottenhoff, Tom H. M.
Haks, Marielle C.
Traore, Boubacar
Kirkness, Ewen F.
Sauerwein, Robert W.
Crompton, Peter D.
TI Transcriptomic evidence for modulation of host inflammatory responses
during febrile Plasmodium falciparum malaria
SO SCIENTIFIC REPORTS
LA English
DT Article
ID DIFFERENTIAL EXPRESSION ANALYSIS; ACQUIRED-IMMUNITY; GENE-EXPRESSION;
PERIPHERAL-BLOOD; PROTECTION; INFECTION; CHILDREN; COHORT
AB Identifying molecular predictors and mechanisms of malaria disease is important for understanding how Plasmodium falciparum malaria is controlled. Transcriptomic studies in humans have so far been limited to retrospective analysis of blood samples from clinical cases. In this prospective, proof-of-principle study, we compared whole-blood RNA-seq profiles at pre- and post-infection time points from Malian adults who were either asymptomatic (n = 5) or febrile (n = 3) during their first seasonal PCR-positive P. falciparum infection with those from malaria-naive Dutch adults after a single controlled human malaria infection (n = 5). Our data show a graded activation of pathways downstream of pro-inflammatory cytokines, with the highest activation in malaria-naive Dutch individuals and significantly reduced activation in malaria-experienced Malians. Newly febrile and asymptomatic infections in Malians were statistically indistinguishable except for genes activated by pro-inflammatory cytokines. The combined data provide a molecular basis for the development of a pyrogenic threshold as individuals acquire immunity to clinical malaria.
C1 [Tran, Tuan M.; Skinner, Jeff; Crompton, Peter D.] NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA.
[Tran, Tuan M.] Indiana Univ Sch Med, Dept Med, Div Infect Dis, Indianapolis, IN 46202 USA.
[Jones, Marcus B.; Venepally, Pratap; Kirkness, Ewen F.] J Craig Venter Inst, Genom Med Grp, Rockville, MD USA.
[Ongoiba, Aissata; Doumbo, Safiatou; Kayentao, Kassoum; Doumbo, Ogobara K.; Traore, Boubacar] Univ Sci Tech & Technol Bamako, Mali Int Ctr Excellence Res, Bamako, Mali.
[Bijker, Else M.; Sauerwein, Robert W.] Radboud Univ Nijmegen, Med Ctr, Dept Med Microbiol, Nijmegen, Netherlands.
[Schats, Remko; Quinten, Edwin; Visser, Leo G.; Ottenhoff, Tom H. M.; Haks, Marielle C.] Leiden Univ, Med Ctr, Dept Infect Dis, Leiden, Netherlands.
[Whalen, Elizabeth; Presnell, Scott; Chaussabel, Damien] Benaroya Res Inst, Syst Immunol Div, Seattle, WA USA.
[O'Connell, Elise M.; Nutman, Thomas B.] NIAID, Parasit Dis Lab, NIH, Bethesda, MD USA.
[Chaussabel, Damien] Sidra Med & Res Ctr, Doha, Qatar.
[Lorenzi, Hernan] J Craig Venter Inst, Infect Dis Grp, Bethesda, MD USA.
RP Tran, TM (reprint author), NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA.; Tran, TM (reprint author), Indiana Univ Sch Med, Dept Med, Div Infect Dis, Indianapolis, IN 46202 USA.
EM tuantran@iu.edu
RI Crompton, Peter/N-1130-2016;
OI Chaussabel, Damien/0000-0002-6131-7242; Skinner,
Jeff/0000-0001-5697-0442
FU National Institute of Allergy and Infectious Diseases, National
Institutes of Health, Department of Health and Human Services
[HHSN272200900007C]; Division of Intramural Research; Netherlands
Organization for Health Research and Development (ZonMw) [m95110086];
Dioraphte Foundation [12010100]
FX We thank the residents of Kalifabougou, Mali and the Dutch volunteers
for participating in this study. This project was supported with federal
funds from the National Institute of Allergy and Infectious Diseases,
National Institutes of Health, Department of Health and Human Services
under contract number HHSN272200900007C and the Division of Intramural
Research. The CHMI trial was supported by The Netherlands Organization
for Health Research and Development (ZonMw) (projectm95110086) and the
Dioraphte Foundation (project 12010100).
NR 41
TC 0
Z9 0
U1 0
U2 4
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 AUG 10
PY 2016
VL 6
AR 31291
DI 10.1038/srep31291
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DS9VP
UT WOS:000381131900002
PM 27506615
ER
PT J
AU Gill, KP
Hung, SSC
Sharov, A
Lo, CY
Needham, K
Lidgerwood, GE
Jackson, S
Crombie, DE
Nayagam, BA
Cook, AL
Hewitt, AW
Pebay, A
Wong, RCB
AF Gill, Katherine P.
Hung, Sandy S. C.
Sharov, Alexei
Lo, Camden Y.
Needham, Karina
Lidgerwood, Grace E.
Jackson, Stacey
Crombie, Duncan E.
Nayagam, Bryony A.
Cook, Anthony L.
Hewitt, Alex W.
Pebay, Alice
Wong, Raymond C. B.
TI Enriched retinal ganglion cells derived from human embryonic stem cells
SO Scientific Reports
LA English
DT Article
ID HEREDITARY OPTIC NEUROPATHY; HUMAN MULLER GLIA; IN-VITRO;
GENE-EXPRESSION; MACULAR DEGENERATION; NEURAL PROGENITORS; HUMAN
BLASTOCYSTS; BRN-3 FAMILY; HUMAN ESCS; GENERATION
AB Optic neuropathies are characterised by a loss of retinal ganglion cells (RGCs) that lead to vision impairment. Development of cell therapy requires a better understanding of the signals that direct stem cells into RGCs. Human embryonic stem cells (hESCs) represent an unlimited cellular source for generation of human RGCs in vitro. In this study, we present a 45-day protocol that utilises magnetic activated cell sorting to generate enriched population of RGCs via stepwise retinal differentiation using hESCs. We performed an extensive characterization of these stem cell-derived RGCs by examining the gene and protein expressions of a panel of neural/RGC markers. Furthermore, whole transcriptome analysis demonstrated similarity of the hESC-derived RGCs to human adult RGCs. The enriched hESC-RGCs possess long axons, functional electrophysiological profiles and axonal transport of mitochondria, suggestive of maturity. In summary, this RGC differentiation protocol can generate an enriched population of functional RGCs from hESCs, allowing future studies on disease modeling of optic neuropathies and development of cell therapies.
C1 [Gill, Katherine P.; Hung, Sandy S. C.; Lidgerwood, Grace E.; Jackson, Stacey; Crombie, Duncan E.; Hewitt, Alex W.; Pebay, Alice; Wong, Raymond C. B.] Univ Melbourne, Ctr Eye Res Australia, Royal Victorian Eye & Ear Hosp, Melbourne, Vic 3010, Australia.
[Gill, Katherine P.; Hung, Sandy S. C.; Lidgerwood, Grace E.; Jackson, Stacey; Crombie, Duncan E.; Hewitt, Alex W.; Pebay, Alice; Wong, Raymond C. B.] Univ Melbourne, Dept Surg, Ophthalmol, Melbourne, Vic 3010, Australia.
[Sharov, Alexei] NIA, NIH, Bethesda, MD 20892 USA.
[Lo, Camden Y.] Monash Univ, Monash Micro Imaging, Clayton, Vic 3800, Australia.
[Needham, Karina] Univ Melbourne, Dept Otolaryngol, Melbourne, Vic 3010, Australia.
[Needham, Karina] Univ Melbourne, Dept Surg, Melbourne, Vic 3010, Australia.
[Needham, Karina] Royal Victorian Eye & Ear Hosp, East Melbourne, Vic, Australia.
[Nayagam, Bryony A.] Univ Melbourne, Dept Audiol & Speech Pathol, Melbourne, Vic 3010, Australia.
[Nayagam, Bryony A.] Univ Melbourne, Dept Ophthalmol, Melbourne, Vic 3010, Australia.
[Cook, Anthony L.] Univ Tasmania, Wicking Dementia Res & Educ Ctr, Hobart, Tas 7001, Australia.
[Hewitt, Alex W.] Univ Tasmania, Menzies Inst Med Res, Sch Med, Hobart, Tas 7001, Australia.
RP Pebay, A; Wong, RCB (reprint author), Univ Melbourne, Ctr Eye Res Australia, Royal Victorian Eye & Ear Hosp, Melbourne, Vic 3010, Australia.; Pebay, A; Wong, RCB (reprint author), Univ Melbourne, Dept Surg, Ophthalmol, Melbourne, Vic 3010, Australia.
EM apebay@unimelb.edu.au; wongcb@unimelb.edu.au
OI Cook, Anthony/0000-0003-1770-7910
FU National Health and Medical Research Council [1084256]; Bright Focus
Foundation; University of Melbourne; Retina Australia; Ophthalmic
Research Institute of Australia; National Stem Cell Foundation of
Australia; Clifford Craig Medical Research Trust [133]; NHMRC Career
Development Fellowship [1004164]; NHMRC Early Career Fellowship;
NHMRC-CSL Gustav Nossal postgraduate research scholarship; Australian
Research Council Future Fellowship [FT140100047]; Cranbourne Foundation
Fellowship; Australian Postgraduate Award; Garnett Passe and Rodney
Williams Memorial Foundation Research Fellowship; Senior Wagstaff
Fellowship in Otolaryngology; Intramural Research Program of the
National Institute on Aging
FX This work was supported by grants from the National Health and Medical
Research Council (RCBW, 1084256), Bright Focus Foundation (AWH, AP), the
University of Melbourne (RCBW, AP), Retina Australia (RCBW, SSCH, AWH,
AP) the Ophthalmic Research Institute of Australia (RCBW, SSCH, AWH,
AP), National Stem Cell Foundation of Australia (AP), Clifford Craig
Medical Research Trust (#133, ALC, AWH, AP), a NHMRC Career Development
Fellowship (AP, 1004164), a NHMRC Early Career Fellowship (AWH), a
NHMRC-CSL Gustav Nossal postgraduate research scholarship (DEC), an
Australian Research Council Future Fellowship (AP, FT140100047), a
Cranbourne Foundation Fellowship (RCBW), an Australian Postgraduate
Award (KPG), a Garnett Passe and Rodney Williams Memorial Foundation
Research Fellowship (BAN), a Senior Wagstaff Fellowship in
Otolaryngology (KN), Intramural Research Program of the National
Institute on Aging (AS) and operational infrastructure support from the
Victorian Government.
NR 67
TC 0
Z9 0
U1 4
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 AUG 10
PY 2016
VL 6
AR 30552
DI 10.1038/srep30552
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DS9RL
UT WOS:000381120900001
PM 27506453
ER
PT J
AU Nagmetova, G
Yagofarova, A
Berdimuratova, K
Kurmanbayev, A
AF Nagmetova, Gulden
Yagofarova, Almira
Berdimuratova, Kalysh
Kurmanbayev, Askar
TI Evaluating the performance of electrogenic strains of bacteria in
microbial fuel cells
SO JOURNAL OF BIOTECHNOLOGY
LA English
DT Meeting Abstract
CT European Biotechnology Conference
CY MAY 05-07, 2016
CL LATVIA
C1 [Nagmetova, Gulden] LN Gumilyov Eurasian Natl Univ, Fac Nat Sci, Astana, Kazakhstan.
[Yagofarova, Almira; Berdimuratova, Kalysh; Kurmanbayev, Askar] Natl Biotechnol Ctr, Lab Ecol Biotechnol, Astana, Kazakhstan.
EM solnce30-04@mail.ru
NR 0
TC 0
Z9 0
U1 6
U2 6
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0168-1656
EI 1873-4863
J9 J BIOTECHNOL
JI J. Biotechnol.
PD AUG 10
PY 2016
VL 231
SU S
BP S74
EP S74
DI 10.1016/j.jbiotec.2016.05.270
PG 1
WC Biotechnology & Applied Microbiology
SC Biotechnology & Applied Microbiology
GA DR9TZ
UT WOS:000380240300231
ER
PT J
AU Duplat-Bermudez, L
Ruiz-Medrano, R
Landsman, D
Marino-Ramirez, L
Xoconostle-Cazares, B
AF Duplat-Bermudez, L.
Ruiz-Medrano, R.
Landsman, D.
Marino-Ramirez, L.
Xoconostle-Cazares, B.
TI Transcriptomic analysis of Arabidopsis overexpressing flowering locus T
driven by a meristem-specific promoter that induces early flowering
SO GENE
LA English
DT Article
DE Arabidopsis; Flowering locus T; RNA-seq analysis; Plant development;
Transgenic plants
ID LARGE GENE LISTS; RNA-SEQ; FLORAL INDUCTION; FT PROTEIN; PHYSIOLOGICAL
ANALYSIS; EXPRESSION ANALYSIS; PATHWAY INTEGRATOR; LIGHT QUALITY;
SEASONAL CUES; THALIANA
AB Here we analyzed in leaves the effect of FT overexpression driven by meristem-specific KNAT1 gene homolog of Arabidopsis thaliana (Lincoln et al., 1994; Long et al., 1996) on the transcriptomic response during plant development. Our results demonstrated that meristematic FT overexpression generates a phenotype with an early flowering independent of photoperiod when compared with wild type (WT) plants. Arabidopsis FT-overexpressor lines (AtFTOE) did not show significant differences compared with WT lines neither in leaf number nor in rosette diameter up to day 21, when AtFTOE flowered. After this period AtFTOE plants started flower production and no new rosette leaves were produced. Additionally, WT plants continued on vegetative stage up to day 40, producing 12-14 rosette leaves before flowering. Transcriptomic analysis of rosette leaves studied by sequencing lllumina RNA-seq allowed us to determine the differential expression in mature leaf rosette of 3652 genes, being 626 of them up-regulated and 3026 down-regulated. Overexpressed genes related with flowering showed up-regulated transcription factors such as MADS-box that are known as flowering markers in meristem and which overexpression has been related with meristem identity preservation and the transition from vegetative to floral stage. Genes related with sugar transport have shown a higher demand of monosaccharides derived from the hydrolysis of sucrose to glucose and probably fructose, which can also be influenced by reproductive stage of AtFTOE plants. (C) 2016 Elsevier B.V. All rights reserved.
C1 [Duplat-Bermudez, L.; Ruiz-Medrano, R.; Xoconostle-Cazares, B.] Inst Politecn Nacl, Ctr Invest & Estudios Avanzados, Dept Biotecnol & Bioingn, Av IPN 2508 San Pedro Zacatenco, Mexico City 07360, DF, Mexico.
[Landsman, D.; Marino-Ramirez, L.] NIH, Computat Biol Branch, Natl Ctr Biotechnol Informat, Natl Lib Med, Bldg 10, Bethesda, MD 20892 USA.
RP Xoconostle-Cazares, B (reprint author), Inst Politecn Nacl, Ctr Invest & Estudios Avanzados, Av IPN 2508 San Pedro Zacatenco, Mexico City 07360, DF, Mexico.
EM bxoconos@cinvestav.mx
OI Marino-Ramirez, Leonardo/0000-0002-5716-8512; Landsman,
David/0000-0002-9819-6675
FU CINVESTAV-IPN; CONACyT [156162, 105985, 388937]; SENASICA-SAGARPA grant;
Intramural Research Program of the NIH, NLM, NCBI
FX This work was supported by departmental funds from CINVESTAV-IPN, by
CONACyT grant nos. 156162 to RR-M and 105985 to BX-C, and a
SENASICA-SAGARPA grant to BX-C and RR-M. LD-B was supported by a
doctoral fellowship from CONACyT no 388937. This research was partially
supported by the Intramural Research Program of the NIH, NLM, NCBI. We
are grateful to the members of the laboratory of Plant Biotechnology for
critical comments to this manuscript.
NR 79
TC 0
Z9 0
U1 14
U2 51
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0378-1119
EI 1879-0038
J9 GENE
JI Gene
PD AUG 10
PY 2016
VL 587
IS 2
BP 120
EP 131
DI 10.1016/j.gene.2016.04.060
PG 12
WC Genetics & Heredity
SC Genetics & Heredity
GA DO5MQ
UT WOS:000377827600002
PM 27154816
ER
PT J
AU Bhattacharyya, T
Jha, S
Wang, HY
Kastner, DL
Remmers, EF
AF Bhattacharyya, Timothy
Jha, Smita
Wang, Hongying
Kastner, Daniel L.
Remmers, Elaine F.
TI Hypophosphatasia and the risk of atypical femur fractures: a
case-control study
SO BMC MUSCULOSKELETAL DISORDERS
LA English
DT Article
ID BISPHOSPHONATE USE; FEMORAL FRACTURES; DIAPHYSEAL FRACTURES; STRESS;
SHAFT
AB Background: Case reports have linked adult hypophosphatasia as a possible cause of atypical femur fractures (AFF) associated with bisphosphonate use. Adult hypophosphatasia is an asymptomatic genetic condition which results in low alkaline phosphatase and elevated pyridoxal phosphate. We conducted a case- control study to assess the role of hypophosphatasia and atypical femur fracture.
Methods: We recruited 13 control patients who took long term bisphosphonates without complication and 10 patients who sustained atypical femur fractures (mean bisphosphonate use, 9 years both cohorts). Patients underwent clinical exam and measurement of alkaline phosphatase and pyridoxal phosphate (PLP) levels. In addition, DNA was extracted and the ALPL gene was sequenced in both cohorts.
Results: Low alkaline phosphatase levels (< 55 U/L) were seen in 5/10 AFF patients and 5/13 control patients. Two control patients demonstrated low alkaline phosphatase levels and elevated PLP. The alkaline phosphatase (ALPL) gene exons and intron splice sites were sequenced in the atypical femur fracture and control cohorts and no coding mutations were identified in any subjects. Atypical femur fracture patients demonstrated more varus hip alignment (p < 0.048) with no significant difference in mechanical axis.
Conclusions: We found no evidence of hypophosphatasia as a risk factor for atypical femur fractures. Laboratory findings of mildly low alkaline phosphatase activity were equally common in atypical and control cohorts and may be due to long term bisphosphonate use.
C1 [Bhattacharyya, Timothy] NIAMSD, NIH, 10 Ctr Dr,Mail Code 1468, Bethesda, MD 20892 USA.
[Jha, Smita] Natl Inst Child Hlth & Human Dev NICHD, NIH, Bethesda, MD USA.
[Wang, Hongying; Kastner, Daniel L.; Remmers, Elaine F.] NHGRI, Inflammatory Dis Sect, Med Genet Branch, NIH, Bethesda, MD 20892 USA.
RP Bhattacharyya, T (reprint author), NIAMSD, NIH, 10 Ctr Dr,Mail Code 1468, Bethesda, MD 20892 USA.
EM timothy.bhattacharyya@nih.gov
FU Intramural Research Programs of the National Institute of Arthritis and
Musculoskeletal and Skin Diseases, National Human Genome Research
Institute
FX The study was funded by the Intramural Research Programs of the National
Institute of Arthritis and Musculoskeletal and Skin Diseases, National
Human Genome Research Institute. The funding bodies had no role in the
collection of data or review of the manuscript.
NR 18
TC 1
Z9 1
U1 0
U2 0
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2474
J9 BMC MUSCULOSKEL DIS
JI BMC Musculoskelet. Disord.
PD AUG 9
PY 2016
VL 17
AR 332
DI 10.1186/s12891-016-1191-8
PG 4
WC Orthopedics; Rheumatology
SC Orthopedics; Rheumatology
GA EM0OC
UT WOS:000395016600001
PM 27507156
ER
PT J
AU Nakamura, Y
Harada, T
Nagaya, T
Sato, K
Okuyama, S
Choyke, PL
Kobayashi, H
AF Nakamura, Yuko
Harada, Toshiko
Nagaya, Tadanobu
Sato, Kazuhide
Okuyama, Shuhei
Choyke, Peter L.
Kobayashi, Hisataka
TI Dynamic fluorescent imaging with the activatable probe, gamma-glutamyl
hydroxymethyl rhodamine green in the detection of peritoneal cancer
metastases: Overcoming the problem of dilution when using a sprayable
optical probe
SO ONCOTARGET
LA English
DT Article
DE kinetic map; green emitting probe; autofluorescence;
gamma-glutamyltranspeptidase; peritoneal cancer metastases
ID KILLER-REPORTER ADENOVIRUS; IN-VIVO; GUIDED SURGERY; MOLECULAR PROBES;
DRUG-RESISTANCE; LIVE MOUSE; TUMORS; TRANSFERASE; EXPRESSION; CELLS
AB Optical fluorescence-guided imaging is increasingly used to guide surgery and endoscopic procedures. Activatable probes are particularly useful because of high target-to-background ratios that increase sensitivity for tiny cancer foci. However, green fluorescent activatable probes suffer from interference from autofluorescence found in biological tissue. The purpose of this study was to determine if dynamic imaging can be used to differentiate specific fluorescence arising from an activated probe in a tumor from autofluorescence in background tissues especially when low concentrations of the dye are applied. Serial fluorescence imaging was performed using various concentrations of gamma-glutamyl hydroxymethyl rhodamine green (gGlu-HMRG) which was sprayed on the peritoneal surface with tiny implants of SHIN3-DsRed ovarian cancer tumors. Temporal differences in signal between specific green fluorescence in cancer foci and non-specific autofluorescence in background tissue were measured at 5, 10, 20 and 30 min after application of gGlu-HMRG and were processed into three kinetic maps reflecting maximum fluorescence signal (MF), wash-in rate (WIR), and area under the curve (AUC), respectively. Using concentrations up to 10 mu M of gGlu-HMRG, the fluorescence intensity of cancer foci was significantly higher than that of small intestine but only at 30 min. However, on kinetic maps derived from dynamic fluorescence imaging, the signal of cancer foci was significantly higher than that of small intestine after only 5 min even at concentrations as low as 2.5 mu M of gGlu-HMRG (p < 0.01). At lower concentrations, kinetic maps derived from dynamic fluorescence imaging were superior to unprocessed images for cancer detection.
C1 [Nakamura, Yuko; Harada, Toshiko; Nagaya, Tadanobu; Sato, Kazuhide; Okuyama, Shuhei; 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 Institute of Health,
National Cancer Institute, Center for Cancer Research
FX This research was supported by the Intramural Research Program of the
National Institute of Health, National Cancer Institute, Center for
Cancer Research.
NR 42
TC 0
Z9 0
U1 4
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 AUG 9
PY 2016
VL 7
IS 32
BP 51124
EP 51137
DI 10.18632/oncotarget.9898
PG 14
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA DY9CC
UT WOS:000385429100030
PM 27286461
ER
PT J
AU Earl, LA
Subramaniam, S
AF Earl, Lesley A.
Subramaniam, Sriram
TI Cryo-EM of viruses and vaccine design
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Editorial Material
ID HUMAN RHINOVIRUS C; CRYOELECTRON MICROSCOPY; ELECTRON CRYOMICROSCOPY;
CHILDREN; PROTEIN
C1 [Earl, Lesley A.; Subramaniam, Sriram] NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bldg 37, Bethesda, MD 20892 USA.
RP Subramaniam, S (reprint author), NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bldg 37, Bethesda, MD 20892 USA.
EM ss1@nih.gov
NR 20
TC 1
Z9 1
U1 2
U2 2
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 AUG 9
PY 2016
VL 113
IS 32
BP 8903
EP 8905
DI 10.1073/pnas.1609721113
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DT2EJ
UT WOS:000381293300036
PM 27482113
ER
PT J
AU Aksoyoglu, MA
Podgornik, R
Bezrukov, SM
Gurnev, PA
Muthukumar, M
Parsegian, VA
AF Aksoyoglu, M. Alphan
Podgornik, Rudolf
Bezrukov, Sergey M.
Gurnev, Philip A.
Muthukumar, Murugappan
Parsegian, V. Adrian
TI Size-dependent forced PEG partitioning into channels: VDAC, OmpC, and
alpha-hemolysin
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE beta-barrel pores; nanopore-based sensing; polymer confinement; polymer
transport; macromolecular crowding
ID MOLECULE MASS-SPECTROMETRY; ACCESS RESISTANCE; FLEXIBLE POLYMERS;
PROTEIN STABILITY; ION-CHANNEL; PORE; NANOPORE; CONDUCTIVITY;
CONDUCTANCE; MEMBRANE
AB Nonideal polymer mixtures of PEGs of different molecular weights partition differently into nanosize protein channels. Here, we assess the validity of the recently proposed theoretical approach of forced partitioning for three structurally different beta-barrel channels: voltage-dependent anion channel from outer mitochondrial membrane VDAC, bacterial porin OmpC (outer membrane protein C), and bacterial channel-forming toxin alpha-hemolysin. Our interpretation is based on the idea that relatively less-penetrating polymers push the more easily penetrating ones into nanosize channels in excess of their bath concentration. Comparison of the theory with experiments is excellent for VDAC. Polymer partitioning data for the other two channels are consistent with theory if additional assumptions regarding the energy penalty of pore penetration are included. The obtained results demonstrate that the general concept of "polymers pushing polymers" is helpful in understanding and quantification of concrete examples of size-dependent forced partitioning of polymers into protein nanopores.
C1 [Aksoyoglu, M. Alphan; Podgornik, Rudolf; Gurnev, Philip A.; Parsegian, V. Adrian] Univ Massachusetts, Dept Phys, Amherst, MA 01003 USA.
[Podgornik, Rudolf] Univ Ljubljana, Dept Phys, Fac Math & Phys, Ljubljana 1000, Slovenia.
[Podgornik, Rudolf] J Stefan Inst, Dept Theoret Phys, Ljubljana 1000, Slovenia.
[Bezrukov, Sergey M.; Gurnev, Philip A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Mol Transport, NIH, Bethesda, MD 20892 USA.
[Muthukumar, Murugappan] Univ Massachusetts, Dept Polymer Sci & Engn, Amherst, MA 01003 USA.
RP Podgornik, R (reprint author), Univ Massachusetts, Dept Phys, Amherst, MA 01003 USA.; Podgornik, R (reprint author), Univ Ljubljana, Dept Phys, Fac Math & Phys, Ljubljana 1000, Slovenia.; Podgornik, R (reprint author), J Stefan Inst, Dept Theoret Phys, Ljubljana 1000, Slovenia.; Bezrukov, SM (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Mol Transport, NIH, Bethesda, MD 20892 USA.
EM rudolf.podgornik@ijs.si; bezrukos@mail.nih.gov
FU US Department of Energy, Office of Basic Energy Sciences, Division of
Materials Sciences and Engineering Award [DE-SC0008176]; Intramural
Research Program of the NIH, Eunice Kennedy Shriver National Institute
of Child Health and Human Development; National Science Foundation EAGER
Award [1249199]; National Science Foundation [DMR-1504265]; Air Force
Office of Scientific Research Grant [FA9550-14-1-0164]; NIH
[R01HG002776-11]
FX This work was supported by US Department of Energy, Office of Basic
Energy Sciences, Division of Materials Sciences and Engineering Award
DE-SC0008176 (to M.A.A., V.A.P., and R.P.); the Intramural Research
Program of the NIH, Eunice Kennedy Shriver National Institute of Child
Health and Human Development (S.M.B. and P.A.G.); National Science
Foundation EAGER Award 1249199 (to P.A.G.); and National Science
Foundation Grant DMR-1504265, Air Force Office of Scientific Research
Grant FA9550-14-1-0164, and NIH Grant R01HG002776-11 (all to M.M.).
NR 40
TC 2
Z9 2
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 AUG 9
PY 2016
VL 113
IS 32
BP 9003
EP 9008
DI 10.1073/pnas.1602716113
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DT2EJ
UT WOS:000381293300053
PM 27466408
ER
PT J
AU Won, S
Incontro, S
Nicoll, RA
Roche, KW
AF Won, Sehoon
Incontro, Salvatore
Nicoll, Roger A.
Roche, Katherine W.
TI PSD-95 stabilizes NMDA receptors by inducing the degradation of STEP61
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE PSD-95; NMDA receptor; STEP; ubiquitination
ID PROTEIN-TYROSINE-PHOSPHATASE; D-ASPARTATE RECEPTOR; LONG-TERM
POTENTIATION; DISEASE MOUSE MODEL; ALZHEIMERS-DISEASE; MOLECULAR
CHARACTERIZATION; GLUTAMATE RECEPTORS; SYNAPTIC PLASTICITY; C-TERMINUS;
SUBUNIT
AB Phosphorylation regulates surface and synaptic expression of NMDA receptors (NMDARs). Both the tyrosine kinase Fyn and the tyrosine phosphatase striatal-enriched protein tyrosine phosphatase (STEP) are known to target the NMDA receptor subunit GluN2B on tyrosine 1472, which is a critical residue that mediates NMDAR endocytosis. STEP reduces the surface expression of NMDARs by promoting dephosphorylation of GluN2B Y1472, whereas the synaptic scaffolding protein postsynaptic density protein 95 (PSD-95) stabilizes the surface expression of NMDARs. However, nothing is known about a potential functional interaction between STEP and PSD-95. We now report that STEP61 binds to PSD-95 but not to other PSD-95 family members. We find that PSD-95 expression destabilizes STEP61 via ubiquitination and degradation by the proteasome. Using subcellular fractionation, we detect low amounts of STEP61 in the PSD fraction. However, STEP61 expression in the PSD is increased upon knockdown of PSD-95 or in vivo as detected in PSD-95-KO mice, demonstrating that PSD-95 excludes STEP61 from the PSD. Importantly, only extrasynaptic NMDAR expression and currents were increased upon STEP knockdown, as is consistent with low STEP61 localization in the PSD. Our findings support a dual role for PSD-95 in stabilizing synaptic NMDARs by binding directly to GluN2B but also by promoting synaptic exclusion and degradation of the negative regulator STEP61.
C1 [Won, Sehoon; Roche, Katherine W.] NINDS, Receptor Biol Sect, NIH, Bethesda, MD 20892 USA.
[Incontro, Salvatore; Nicoll, Roger A.] Univ Calif San Francisco, Dept Mol & Cellular Pharmacol, San Francisco, CA 94158 USA.
[Nicoll, Roger A.] Univ Calif San Francisco, Dept Physiol, San Francisco, CA 94158 USA.
RP Roche, KW (reprint author), NINDS, Receptor Biol Sect, NIH, Bethesda, MD 20892 USA.; Nicoll, RA (reprint author), Univ Calif San Francisco, Dept Mol & Cellular Pharmacol, San Francisco, CA 94158 USA.; Nicoll, RA (reprint author), Univ Calif San Francisco, Dept Physiol, San Francisco, CA 94158 USA.
EM rochek@ninds.nih.gov; nicoll@cmp.ucsf.edu
OI Roche, Katherine/0000-0001-7282-6539
FU NINDS Intramural Research Program; National Institute of Mental Health
Grant [MH-38256]
FX We thank John D. Badger II for technical assistance and the National
Institute of Neurological Disorders and Stroke (NINDS) imaging facility
for their assistance. This research was supported by the NINDS
Intramural Research Program (S.W. and K.W.R.) and by National Institute
of Mental Health Grant MH-38256 (S.I. and R.A.N.).
NR 53
TC 1
Z9 1
U1 5
U2 5
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 AUG 9
PY 2016
VL 113
IS 32
BP E4736
EP E4744
DI 10.1073/pnas.1609702113
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DT2EJ
UT WOS:000381293300022
PM 27457929
ER
PT J
AU Maurer, CW
LaFaver, K
Ameli, R
Epstein, SA
Hallett, M
Horovitz, SG
AF Maurer, Carine W.
LaFaver, Kathrin
Ameli, Rezvan
Epstein, Steven A.
Hallett, Mark
Horovitz, Silvina G.
TI Impaired self-agency in functional movement disorders A resting-state
fMRI study
SO NEUROLOGY
LA English
DT Article
ID CONVERSION DISORDER; CONNECTIVITY; EXPERIENCE; SENSE; FLUCTUATIONS;
DEPRESSION; NEUROLOGY; STRATEGY; CORTEX; TREMOR
AB Objective: To investigate the neural mechanisms underlying impaired self-agency in patients with functional movement disorders using resting-state functional MRI (fMRI).
Methods: We obtained resting-state fMRI on 35 patients with clinically definite functional movement disorders and 35 age-and sex-matched healthy controls. Between-group differences in functional connectivity from the right temporo-parietal junction (TPJ), a region previously demonstrated to play a critical role in self-agency by comparing internal predictions of movement with actual external events, were assessed using t tests. All participants were screened for psychiatric diagnoses using a structured clinical interview and completed the Beck Depression Inventory and Childhood Trauma Questionnaire.
Results: Compared to the healthy controls, patients with functional movement disorders showed decreased functional connectivity between the right TPJ and the right sensorimotor cortex, cerebellar vermis, bilateral supplementary motor area, and right insula. These findings were independent of depression, anxiety, and childhood trauma scores included in our assessment as covariates.
Conclusions: The decreased functional connectivity between the right TPJ and bilateral sensorimotor regions observed in patients with functional movement disorders supports a model whereby impaired motor feed-forward together with altered sensory feedback from sensorimotor regions and areas of sensorimotor integration to the right TPJ contributes to patients' impaired sense of self-agency.
C1 [Maurer, Carine W.; LaFaver, Kathrin; Hallett, Mark; Horovitz, Silvina G.] Natl Inst Neurol Disorders & Stroke, Human Motor Control Sect, Med Neurol Branch, Bethesda, MD 20824 USA.
[Ameli, Rezvan] NIMH, Expt Therapeut & Pathophysiol Branch, NIH, Bethesda, MD 20892 USA.
[LaFaver, Kathrin] Univ Louisville, Dept Neurol, Louisville, KY 40292 USA.
[Epstein, Steven A.] Georgetown Univ, Dept Psychiat, Washington, DC USA.
RP Maurer, CW (reprint author), Natl Inst Neurol Disorders & Stroke, Human Motor Control Sect, Med Neurol Branch, Bethesda, MD 20824 USA.
EM carine.maurer@nih.gov
FU National Institute of Neurological Disorders and Stroke Intramural
Research Program
FX Supported by the National Institute of Neurological Disorders and Stroke
Intramural Research Program.
NR 35
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U1 4
U2 4
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 AUG 9
PY 2016
VL 87
IS 6
BP 564
EP 570
DI 10.1212/WNL.0000000000002940
PG 7
WC Clinical Neurology
SC Neurosciences & Neurology
GA DU6LT
UT WOS:000382327000009
PM 27385746
ER
PT J
AU Chen, KY
Cypess, AM
Laughlin, MR
Haft, CR
Hu, HH
Bredella, MA
Enerback, S
Kinahan, PE
Lichtenbelt, WV
Lin, FI
Sunderland, JJ
Virtanen, KA
Wahl, RL
AF Chen, Kong Y.
Cypess, Aaron M.
Laughlin, Maren R.
Haft, Carol R.
Hu, Houchun Harry
Bredella, Miriam A.
Enerback, Sven
Kinahan, Paul E.
Lichtenbelt, Wouter van Marken
Lin, Frank I.
Sunderland, John J.
Virtanen, Kirsi A.
Wahl, Richard L.
TI Brown Adipose Reporting Criteria in Imaging STudies (BARCIST 1.0):
Recommendations for Standardized FDG-PET/CT Experiments in Humans
SO CELL METABOLISM
LA English
DT Review
ID POSITRON-EMISSION-TOMOGRAPHY; TYPE-2 DIABETES-MELLITUS; ADULT HUMANS;
F-18-FDG PET/CT; ENERGY-EXPENDITURE; OXIDATIVE-METABOLISM; INSULIN
SENSITIVITY; COMPUTED-TOMOGRAPHY; TISSUE ACTIVITY; COLD-EXPOSURE
AB Human brown adipose tissue (BAT) presence, metabolic activity, and estimated mass are typically measured by imaging [18F]fluorodeoxyglucose (FDG) uptake in response to cold exposure in regions of the body expected to contain BAT, using positron emission tomography combined with X-ray computed tomography (FDG-PET/CT). Efforts to describe the epidemiology and biology of human BAT are hampered by diverse experimental practices, making it difficult to directly compare results among laboratories. An expert panel was assembled by the National Institute of Diabetes and Digestive and Kidney Diseases on November 4, 2014 to discuss minimal requirements for conducting FDG-PET/CT experiments of human BAT, data analysis, and publication of results. This resulted in Brown Adipose Reporting Criteria in Imaging STudies (BARCIST 1.0). Since there are no fully validated best practices at this time, panel recommendations are meant to enhance comparability across experiments, but not to constrain experimental design or the questions that can be asked.
C1 [Chen, Kong Y.; Cypess, Aaron M.; Laughlin, Maren R.; Haft, Carol R.] NIDDK, NIH, Bethesda, MD 20892 USA.
[Hu, Houchun Harry] Phoenix Childrens Hosp, Phoenix, AZ 85016 USA.
[Bredella, Miriam A.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Bredella, Miriam A.] Harvard Med Sch, Boston, MA 02114 USA.
[Enerback, Sven] Univ Gothenburg, S-40530 Gothenburg, Sweden.
[Kinahan, Paul E.] Univ Washington, Seattle, WA 98105 USA.
[Lichtenbelt, Wouter van Marken] Maastricht Univ, NL-6211 LK Maastricht, Netherlands.
[Lin, Frank I.] NCI, NIH, Bethesda, MD 20892 USA.
[Sunderland, John J.] Univ Iowa, Iowa City, IA 52242 USA.
[Virtanen, Kirsi A.] Turku Univ Hosp, Turku 20500, Finland.
[Virtanen, Kirsi A.] Univ Turku, SF-20500 Turku, Finland.
[Wahl, Richard L.] Washington Univ, Sch Med, Mallinckrodt Inst Radiol, St Louis, MO 63110 USA.
RP Chen, KY; Cypess, AM; Laughlin, MR (reprint author), NIDDK, NIH, Bethesda, MD 20892 USA.
EM kong.chen@nih.gov; aaron.cypess@nih.gov; maren.laughlin@nih.gov
OI Chen, Kong/0000-0002-0306-1904
FU Intramural Research Program of the NIH; National Institute of Diabetes
and Digestive and Kidney Diseases (NIDDK); National Cancer Institute
(NCI)
FX This research was supported in part by the Intramural Research Program
of the NIH, The National Institute of Diabetes and Digestive and Kidney
Diseases (NIDDK), and the National Cancer Institute (NCI).
NR 74
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U1 3
U2 3
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 AUG 9
PY 2016
VL 24
IS 2
BP 210
EP 222
DI 10.1016/j.cmet.2016.07.014
PG 13
WC Cell Biology; Endocrinology & Metabolism
SC Cell Biology; Endocrinology & Metabolism
GA DT3PH
UT WOS:000381392800010
PM 27508870
ER
PT J
AU Cox, PJ
Kirk, T
Ashmore, T
Willerton, K
Evans, R
Smith, A
Murray, AJ
Stubbs, B
West, J
McLure, SW
King, MT
Dodd, MS
Holloway, C
Neubauer, S
Drawer, S
Veech, RL
Griffin, JL
Clarke, K
AF Cox, Pete J.
Kirk, Tom
Ashmore, Tom
Willerton, Kristof
Evans, Rhys
Smith, Alan
Murray, Andrew J.
Stubbs, Brianna
West, James
McLure, Stewart W.
King, M. Todd
Dodd, Michael S.
Holloway, Cameron
Neubauer, Stefan
Drawer, Scott
Veech, Richard L.
Griffin, Julian L.
Clarke, Kieran
TI Nutritional Ketosis Alters Fuel Preference and Thereby Endurance
Performance in Athletes
SO CELL METABOLISM
LA English
DT Article
ID HUMAN METABOLIC RESPONSE; HUMAN SKELETAL-MUSCLE; FATTY-ACID CYCLE;
KETONE-BODIES; PROLONGED EXERCISE; CALORIC RESTRICTION;
INSULIN-RESISTANCE; OXIDATION RATES; KETOGENIC DIET; NICOTINIC-ACID
AB Ketosis, the metabolic response to energy crisis, is a mechanism to sustain life by altering oxidative fuel selection. Often overlooked for its metabolic potential, ketosis is poorly understood outside of starvation or diabetic crisis. Thus, we studied the biochemical advantages of ketosis in humans using a ketone ester-based form of nutrition without the unwanted milieu of endogenous ketone body production by caloric or carbohydrate restriction. In five separate studies of 39 high-performance athletes, we show how this unique metabolic state improves physical endurance by altering fuel competition for oxidative respiration. Ketosis decreased muscle glycolysis and plasma lactate concentrations, while providing an alternative substrate for oxidative phosphorylation. Ketosis increased intramuscular triacylglycerol oxidation during exercise, even in the presence of normal muscle glycogen, co-ingested carbohydrate and elevated insulin. These findings may hold clues to greater human potential and a better understanding of fuel metabolism in health and disease.
C1 [Cox, Pete J.; Kirk, Tom; Willerton, Kristof; Evans, Rhys; Stubbs, Brianna; McLure, Stewart W.; Dodd, Michael S.; Holloway, Cameron; Clarke, Kieran] Univ Oxford, Dept Physiol Anat & Genet, S Parks Rd, Oxford OX1 3PT, England.
[Cox, Pete J.; Holloway, Cameron; Neubauer, Stefan] Univ Oxford, Dept Cardiovasc Med, Oxford OX3 9DU, England.
[Ashmore, Tom; West, James; Griffin, Julian L.] Univ Cambridge, Dept Biochem, Oxford CB1 9NL, England.
[Ashmore, Tom; West, James; Griffin, Julian L.] Univ Cambridge, Cambridge Syst Biol Ctr, Oxford CB1 9NL, England.
[Ashmore, Tom; West, James; Griffin, Julian L.] MRC Human Nutr Res, Oxford CB1 9NL, England.
[Smith, Alan; Drawer, Scott] UK Sport, 40 Bernard St, London WC1N 1ST, England.
[Murray, Andrew J.] Univ Cambridge, Dept Physiol Dev & Neurosci, Cambridge CB2 3EG, England.
[King, M. Todd; Veech, Richard L.] NIAAA, Lab Metab Control, NIH, Rockville, MD 20852 USA.
RP Cox, PJ (reprint author), Univ Oxford, Dept Physiol Anat & Genet, S Parks Rd, Oxford OX1 3PT, England.; Cox, PJ (reprint author), Univ Oxford, Dept Cardiovasc Med, Oxford OX3 9DU, England.
EM petejcox456@gmail.com
FU Defence Advanced Research Projects Agency (DARPA); UK Sport
FX The authors thank Dr. R. Stillion, Dr. O. Faull, E. Carter, Dr. N
Boehlke, and Y Green for their excellent assistance with these studies.
The authors thank the Defence Advanced Research Projects Agency (DARPA)
and UK Sport for funding this work.
NR 47
TC 8
Z9 8
U1 41
U2 51
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 AUG 9
PY 2016
VL 24
IS 2
BP 256
EP 268
DI 10.1016/j.cmet.2016.07.010
PG 13
WC Cell Biology; Endocrinology & Metabolism
SC Cell Biology; Endocrinology & Metabolism
GA DT3PH
UT WOS:000381392800014
PM 27475046
ER
PT J
AU Moon, HY
Becke, A
Berron, D
Becker, B
Sah, N
Benoni, G
Janke, E
Lubejko, ST
Greig, NH
Mattison, JA
Duzel, E
van Praag, H
AF Moon, Hyo Youl
Becke, Andreas
Berron, David
Becker, Benjamin
Sah, Nirnath
Benoni, Galit
Janke, Emma
Lubejko, Susan T.
Greig, Nigel H.
Mattison, Julie A.
Duzel, Emrah
van Praag, Henriette
TI Running-Induced Systemic Cathepsin B Secretion Is Associated with Memory
Function
SO CELL METABOLISM
LA English
DT Article
ID HIPPOCAMPAL NEUROGENESIS; PHYSICAL-EXERCISE; ALZHEIMER-DISEASE;
SKELETAL-MUSCLE; IMPROVE MEMORY; ANNEXIN A2; BRAIN; MICE; NEURONS; CELLS
AB Peripheral processes that mediate beneficial effects of exercise on the brain remain sparsely explored. Here, we show that a muscle secretory factor, cathepsin B (CTSB) protein, is important for the cognitive and neurogenic benefits of running. Proteomic analysis revealed elevated levels of CTSB in conditioned medium derived from skeletal muscle cell cultures treated with AMP-kinase agonist AICAR. Consistently, running increased CTSB levels in mouse gastrocnemius muscle and plasma. Furthermore, recombinant CTSB application enhanced expression of brain-derived neurotrophic factor (BDNF) and doublecortin (DCX) in adult hippocampal progenitor cells through a mechanism dependent on the multifunctional protein P11. In vivo, in CTSB knockout (KO) mice, running did not enhance adult hippocampal neurogenesis and spatial memory function. Interestingly, in Rhesus monkeys and humans, treadmill exercise elevated CTSB in plasma. In humans, changes in CTSB levels correlated with fitness and hippocampus-dependent memory function. Our findings suggest CTSB as a mediator of effects of exercise on cognition.
C1 [Moon, Hyo Youl; Becker, Benjamin; Sah, Nirnath; Benoni, Galit; Janke, Emma; Lubejko, Susan T.; van Praag, Henriette] NIA, Neuroplast & Behav Unit, Lab Neurosci, Baltimore, MD 21224 USA.
[Becke, Andreas; Berron, David; Duzel, Emrah] Univ Magdeburg, Inst Cognit Neurol & Dementia Res, Leipziger Str 44, D-39120 Magdeburg, Germany.
[Duzel, Emrah] German Ctr Neurodegenerat Dis DZNE, Leipziger Str 44, D-39120 Magdeburg, Germany.
[Greig, Nigel H.] NIA, Drug Design & Dev Sect, Translat Gerontol Branch, Baltimore, MD 21224 USA.
[Mattison, Julie A.] NIA, Nonhuman Primate Core, Translat Gerontol Branch, Baltimore, MD 21224 USA.
RP van Praag, H (reprint author), NIA, Neuroplast & Behav Unit, Lab Neurosci, Baltimore, MD 21224 USA.
EM vanpraag17@gmail.com
RI van Praag, Henriette/F-3939-2015
OI van Praag, Henriette/0000-0002-5727-434X
FU BMBF (EnergI Project); National Institute on Aging, Intramural Research
Program; Korean Visiting Scientist Training Award [HI13C1149]; Deutsche
Forschungs Gemeinschaft [SFB 779 TP A7]
FX This work was supported in part by the BMBF (EnergI Project), the
National Institute on Aging, Intramural Research Program, the Korean
Visiting Scientist Training Award (HI13C1149 to H.Y.M.), and the
Deutsche Forschungs Gemeinschaft (SFB 779 TP A7). We thank Drs. Young Ah
Goo and Hyung Won Choi for proteomic analysis, Yang An for statistical
advice, Linda R. Kitabayashi for image preparation, and Bryan Christie
Design for illustration.
NR 41
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U1 14
U2 18
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 AUG 9
PY 2016
VL 24
IS 2
BP 332
EP 340
DI 10.1016/j.cmet.2016.05.025
PG 9
WC Cell Biology; Endocrinology & Metabolism
SC Cell Biology; Endocrinology & Metabolism
GA DT3PH
UT WOS:000381392800020
PM 27345423
ER
PT J
AU Dowd, KA
DeMaso, CR
Pelc, RS
Speer, SD
Smith, ARY
Goo, L
Platt, DJ
Mascola, JR
Graham, BS
Mulligan, MJ
Diamond, MS
Ledgerwood, JE
Pierson, TC
AF Dowd, Kimberly A.
DeMaso, Christina R.
Pelc, Rebecca S.
Speer, Scott D.
Smith, Alexander R. Y.
Goo, Leslie
Platt, Derek J.
Mascola, John R.
Graham, Barney S.
Mulligan, Mark J.
Diamond, Michael S.
Ledgerwood, Julie E.
Pierson, Theodore C.
TI Broadly Neutralizing Activity of Zika Virus-Immune Sera Identifies a
Single Viral Serotype
SO CELL REPORTS
LA English
DT Article
ID ANTIBODY-MEDIATED NEUTRALIZATION; DENGUE VIRUS; CLINICAL-TRIAL;
DOUBLE-BLIND; PHASE-III; INFECTION; FLAVIVIRUSES; VACCINES;
IMMUNOGENICITY; ENHANCEMENT
AB Recent epidemics of Zika virus (ZIKV) have been associated with congenital malformation during pregnancy and Guillain-Barre syndrome. There are two ZIKV lineages (African and Asian) that share >95% amino acid identity. Little is known regarding the ability of neutralizing antibodies elicited against one lineage to protect against the other. We investigated the breadth of the neutralizing antibody response following ZIKV infection by measuring the sensitivity of six ZIKV strains to neutralization by ZIKV-confirmed convalescent human serum or plasma samples. Contemporary Asian and early African ZIKV strains were similarly sensitive to neutralization regardless of the cellular source of virus. Furthermore, mouse immune serum generated after infection with African or Asian ZIKV strains was capable of neutralizing homologous and heterologous ZIKV strains equivalently. Because our study only defines a single ZIKV serotype, vaccine candidates eliciting robust neutralizing antibody responses should inhibit infection of both ZIKV lineages, including strains circulating in the Americas.
C1 [Dowd, Kimberly A.; DeMaso, Christina R.; Pelc, Rebecca S.; Speer, Scott D.; Smith, Alexander R. Y.; Goo, Leslie; Pierson, Theodore C.] NIAID, Viral Pathogenesis Sect, NIH, Bethesda, MD 20892 USA.
[Platt, Derek J.; Diamond, Michael S.] Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA.
[Platt, Derek J.; Diamond, Michael S.] Washington Univ, Sch Med, Dept Mol Microbiol, St Louis, MO 63110 USA.
[Platt, Derek J.; Diamond, Michael S.] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA.
[Platt, Derek J.; Diamond, Michael S.] Washington Univ, Sch Med, Ctr Human Immunol, St Louis, MO 63110 USA.
[Platt, Derek J.; Diamond, Michael S.] Washington Univ, Sch Med, Immunotherapy Programs, St Louis, MO 63110 USA.
[Mascola, John R.; Graham, Barney S.; Ledgerwood, Julie E.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Mulligan, Mark J.] Emory Univ, Sch Med, Dept Med, Hope Clin,Emory Vaccine Ctr,Div Infect Dis, Decatur, GA 30030 USA.
RP Pierson, TC (reprint author), NIAID, Viral Pathogenesis Sect, NIH, Bethesda, MD 20892 USA.
EM piersontc@mail.nih.gov
FU National Institute of Allergy and Infectious Disease; Emory University
School of Medicine; Georgia Research Alliance; Moderna; Sanofi;
Visterra; [R01AI073755]
FX This work was funded by the intramural program of the National Institute
of Allergy and Infectious Disease to the Division of Intramural Research
and the Vaccine Research Center and extramural grant R01AI073755 to
M.S.D. M.J.M. was supported by funds from the Emory University School of
Medicine and the Georgia Research Alliance. We thank X. de Lamballerie
(Emergence des Pathologies Virales, Aix-Marseille Universite) and the
European Virus Archive Goes Global (EVAg) for providing the H/PF/2013
ZIKV strain and Stephen S. Whitehead (NIAID) for the Brazil Paraiba/2015
virus. We are grateful to the subjects for providing research samples
and to Ingelise Gordon (VRC), Pamela Costner (VRC), Adam Dezure (VRC),
Lilin Lai (Emory), Natalie Thornburg (Emory), Henry Wu (Emory), Srilatha
Edupuganti (Emory), Allison Beck, (Emory), Sree Aramgam (Emory), and
Pamela Lankford-Turner (Emory) for assistance with ZIKV patients and the
collection of samples. We also thank Amanda Feldpausch (Georgia
Department of Health), Jennifer Govero (Washington University), and
Estefania Fernandez (Washington University) for their help with these
studies. M.S.D. is a consultant for Inbios, Visterra, Sanofi, and Takeda
Pharmaceuticals, is on the Scientific Advisory Boards of Moderna and
OraGene, and is a recipient of research grants from Moderna, Sanofi, and
Visterra.
NR 39
TC 13
Z9 15
U1 14
U2 18
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 AUG 9
PY 2016
VL 16
IS 6
BP 1485
EP 1491
DI 10.1016/j.celrep.2016.07.049
PG 7
WC Cell Biology
SC Cell Biology
GA DT3ID
UT WOS:000381373400001
PM 27481466
ER
PT J
AU Liu, JC
Liu, J
Holmstrom, KM
Menazza, S
Parks, RJ
Fergusson, MM
Yu, ZX
Springer, DA
Halsey, C
Liu, C
Murphy, E
Finkel, T
AF Liu, Julia C.
Liu, Jie
Holmstrom, Kira M.
Menazza, Sara
Parks, Randi J.
Fergusson, Maria M.
Yu, Zu-Xi
Springer, Danielle A.
Halsey, Charles
Liu, Chengyu
Murphy, Elizabeth
Finkel, Toren
TI MICU1 Serves as a Molecular Gatekeeper to Prevent In Vivo Mitochondrial
Calcium Overload
SO CELL REPORTS
LA English
DT Article
ID RAT-KIDNEY MITOCHONDRIA; CA2+ UPTAKE; ENDOPLASMIC-RETICULUM; CELL-DEATH;
UNIPORTER; STRESS; MCU; ACTIVATION; PROTEIN; HEART
AB MICU1 is a component of the mitochondrial calcium uniporter, a multiprotein complex that also includes MICU2, MCU, and EMRE. Here, we describe a mouse model of MICU1 deficiency. MICU1(-/-) mitochondria demonstrate altered calcium uptake, and deletion of MICU1 results in significant, but not complete, perinatal mortality. Similar to afflicted patients, viable MICU1(-/-) mice manifest marked ataxia and muscle weakness. Early in life, these animals display a range of biochemical abnormalities, including increased resting mitochondrial calcium levels, altered mitochondrial morphology, and reduced ATP. Older MICU1(-/-) mice show marked, spontaneous improvement coincident with improved mitochondrial calcium handling and an age-dependent reduction in EMRE expression. Remarkably, deleting one allele of EMRE helps normalize calcium uptake while simultaneously rescuing the high perinatal mortality observed in young MICU1(-/-) mice. Together, these results demonstrate that MICU1 serves as a molecular gatekeeper preventing calcium overload and suggests that modulating the calcium uniporter could have widespread therapeutic benefits.
C1 [Liu, Julia C.; Liu, Jie; Holmstrom, Kira M.; Fergusson, Maria M.; Finkel, Toren] NHLBI, Ctr Mol Med, NIH, Bethesda, MD 20892 USA.
[Menazza, Sara; Parks, Randi J.; Murphy, Elizabeth] NHLBI, Syst Biol Ctr, NIH, Bethesda, MD 20892 USA.
[Yu, Zu-Xi] NHLBI, Pathol Core, NIH, Bethesda, MD 20892 USA.
[Springer, Danielle A.] NHLBI, Murine Phenotyping Core, NIH, Bethesda, MD 20892 USA.
[Halsey, Charles] NCI, Lab Canc Biol & Genet, NIH, Bethesda, MD 20892 USA.
[Liu, Chengyu] NHLBI, Transgen Core, NIH, Bethesda, MD 20892 USA.
RP Finkel, T (reprint author), NHLBI, Ctr Mol Med, NIH, Bethesda, MD 20892 USA.
EM finkelt@nih.gov
OI Holmstrom, Kira/0000-0001-6434-7909
FU Intramural NIH funds; Leducq Transatlantic Network grant; PRAT
postdoctoral fellowship from NIGMS
FX We are grateful to Michele Allen for help with mouse phenotyping; Erin
Stempinski, Camron Keshavarz, and Christopher Bleck for help with
electron microscopic analysis; and Jeffrey Culver at the Sanford-Burnham
Orlando Metabolomics Core for skeletal muscle lactate measurements. This
work was supported by Intramural NIH funds, a Leducq Transatlantic
Network grant (to T.F.), and a PRAT postdoctoral fellowship from NIGMS
(to J.C.L.).
NR 46
TC 5
Z9 5
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 AUG 9
PY 2016
VL 16
IS 6
BP 1561
EP 1573
DI 10.1016/j.celrep.2016.07.011
PG 13
WC Cell Biology
SC Cell Biology
GA DT3ID
UT WOS:000381373400009
PM 27477272
ER
PT J
AU Lee, SH
Le Pichon, CE
Adolfsson, O
Gafner, V
Pihlgren, M
Lin, H
Solanoy, H
Brendza, R
Ngu, H
Foreman, O
Chan, R
Ernst, JA
DiCara, D
Hotzel, I
Srinivasan, K
Hansen, DV
Atwal, J
Lu, YM
Bumbaca, D
Pfeifer, A
Watts, RJ
Muhs, A
Scearce-Levie, K
Ayalon, G
AF Lee, Seung-Hye
Le Pichon, Claire E.
Adolfsson, Oskar
Gafner, Valerie
Pihlgren, Maria
Lin, Han
Solanoy, Hilda
Brendza, Robert
Ngu, Hai
Foreman, Oded
Chan, Ruby
Ernst, James A.
DiCara, Danielle
Hotzel, Isidro
Srinivasan, Karpagam
Hansen, David V.
Atwal, Jasvinder
Lu, Yanmei
Bumbaca, Daniela
Pfeifer, Andrea
Watts, Ryan J.
Muhs, Andreas
Scearce-Levie, Kimberly
Ayalon, Gai
TI Antibody-Mediated Targeting of Tau In Vivo Does Not Require Effector
Function and Microglial Engagement
SO CELL REPORTS
LA English
DT Article
ID ALZHEIMERS-DISEASE; TRANSGENIC MICE; PASSIVE-IMMUNIZATION; MOUSE MODEL;
PROTEIN; PATHOLOGY; BRAIN; NEURONS; PHOSPHORYLATION; PROPAGATION
AB The spread of tau pathology correlates with cognitive decline in Alzheimer's disease. In vitro, tau antibodies can block cell-to-cell tau spreading. Although mechanisms of anti-tau function in vivo are unknown, effector function might promote microglia-mediated clearance. In this study, we investigated whether antibody effector function is required for targeting tau. We compared efficacy in vivo and in vitro of two versions of the same tau antibody, with and without effector function, measuring tau pathology, neuron health, and microglial function. Both antibodies reduced accumulation of tau pathology in Tau-P301L transgenic mice and protected cultured neurons against extracellular tau-induced toxicity. Only the full-effector antibody enhanced tau uptake in cultured microglia, which promoted release of proinflammatory cytokines. In neuron-microglia cocultures, only effectorless anti-tau protected neurons, suggesting full-effector tau antibodies can induce indirect toxicity via microglia. We conclude that effector function is not required for efficacy, and effectorless tau antibodies may represent a safer approach to targeting tau.
C1 [Lee, Seung-Hye; Le Pichon, Claire E.; Lin, Han; Solanoy, Hilda; Brendza, Robert; Ngu, Hai; Foreman, Oded; Chan, Ruby; Ernst, James A.; DiCara, Danielle; Hotzel, Isidro; Srinivasan, Karpagam; Hansen, David V.; Atwal, Jasvinder; Lu, Yanmei; Bumbaca, Daniela; Watts, Ryan J.; Scearce-Levie, Kimberly; Ayalon, Gai] Genentech Inc, San Francisco, CA 94080 USA.
[Adolfsson, Oskar; Gafner, Valerie; Pihlgren, Maria; Pfeifer, Andrea; Muhs, Andreas] AC Immune SA, CH-1015 Lausanne, Switzerland.
[Le Pichon, Claire E.] NINDS, NIH, Bethesda, MD 20892 USA.
[Chan, Ruby] Gilead Sci, Foster City, CA 94404 USA.
RP Scearce-Levie, K; Ayalon, G (reprint author), Genentech Inc, San Francisco, CA 94080 USA.; Muhs, A (reprint author), AC Immune SA, CH-1015 Lausanne, Switzerland.
EM andreas.muhs@acimmune.com; kscearcelevie@gmail.com; ayalon.gai@gene.com
NR 37
TC 1
Z9 1
U1 5
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 AUG 9
PY 2016
VL 16
IS 6
BP 1690
EP 1700
DI 10.1016/j.celrep.2016.06.099
PG 11
WC Cell Biology
SC Cell Biology
GA DT3ID
UT WOS:000381373400019
PM 27475227
ER
PT J
AU Jourdain, G
Ngo-Giang-Huong, N
Cressey, TR
Hua, L
Harrison, L
Tierney, C
Salvadori, N
Decker, L
Traisathit, P
Sirirungsi, W
Khamduang, W
Bowonwatanuwong, C
Puthanakit, T
Siberry, GK
Watts, DH
Murphy, TV
Achalapong, J
Hongsiriwon, S
Klinbuayaem, V
Thongsawat, S
Chung, RT
Pol, S
Chotivanich, N
AF Jourdain, Gonzague
Ngo-Giang-Huong, Nicole
Cressey, Tim R.
Hua, Lei
Harrison, Linda
Tierney, Camlin
Salvadori, Nicolas
Decker, Luc
Traisathit, Patrinee
Sirirungsi, Wasna
Khamduang, Woottichai
Bowonwatanuwong, Chureeratana
Puthanakit, Thanyawee
Siberry, George K.
Watts, Diane Heather
Murphy, Trudy V.
Achalapong, Jullapong
Hongsiriwon, Suchat
Klinbuayaem, Virat
Thongsawat, Satawat
Chung, Raymond T.
Pol, Stanislas
Chotivanich, Nantasak
TI Prevention of mother-to-child transmission of hepatitis B virus: a phase
III, placebo-controlled, double-blind, randomized clinical trial to
assess the efficacy and safety of a short course of tenofovir disoproxil
fumarate in women with hepatitis B virus e-antigen
SO BMC INFECTIOUS DISEASES
LA English
DT Article
ID PERINATAL TRANSMISSION; INFANT TRANSMISSION; SURFACE-ANTIGEN; INFECTION;
PREGNANCY; METAANALYSIS
AB Background: Chronic hepatitis B virus (HBV) infection is complicated by cirrhosis and liver cancer. In Thailand, 6-7 % of adults are chronically infected with HBV. The risk of mother-to-child transmission (MTCT) of HBV has been estimated to be about 12 % when mothers have a high hepatitis B viral load, even if infants receive passive-active prophylaxis with HBV immunoglobulin (HBIg) and initiate the hepatitis B vaccine series at birth. We designed a study to assess the efficacy and safety of a short course of maternal tenofovir disoproxil fumarate (TDF) among women with a marker of high viral load for the prevention of MTCT of HBV.
Methods: The study is a phase III, multicenter (17 sites in Thailand), placebo-controlled, double-blind, randomized 1: 1, two-arm clinical trial of TDF 300 mg once daily versus placebo among pregnant women from 28 weeks' gestation through 2-month post-partum. All infants receive HBIg at birth, and a hepatitis B (HB) vaccination series according to Thai guidelines: birth, and age 1, 2, 4 and 6 months. Participant women at study entry must be age >= 18 years, hepatitis B surface antigen (HBsAg) and e-antigen (HBeAg) positive, have alanine aminotransferase (ALT) level < 30 IU/L at screening (confirmed < 60 IU/L pre-entry), negative hepatitis C serology, creatinine clearance > 50 mL/min, and no history of anti-HBV antiviral treatment.
The target sample size of 328 mother/infant pairs assumed 156 evaluable cases per arm to detect a >= 9 % difference in MTCT transmission (3 % experimental arm versus 12 % placebo arm) with 90 % power. Mothers and infants are followed until 12 months after delivery. The primary infant endpoint is detection of HBsAg, confirmed by detection of HBV DNA at six months of age. Secondary endpoints are maternal and infant adverse events, acute exacerbations of maternal hepatitis B disease (ALT > 300 IU/ L, defined as a "flare") following discontinuation of study treatment, infant HBV infection status and growth up to 12 months of age.
Discussion: The results of this randomized trial will clarify the efficacy and safety of a short course of antiviral treatment to prevent mother-to-child transmission of HBV and inform international guidelines.
C1 [Jourdain, Gonzague; Ngo-Giang-Huong, Nicole; Cressey, Tim R.; Salvadori, Nicolas; Decker, Luc] Inst Rech Dev IRD France, PHPT, UMI 174, 187-10 Changklan Rd, Chiang Mai 50100, Thailand.
[Jourdain, Gonzague; Ngo-Giang-Huong, Nicole; Cressey, Tim R.; Salvadori, Nicolas; Decker, Luc; Sirirungsi, Wasna; Khamduang, Woottichai] Chiang Mai Univ, Fac Associated Med Sci, 110 Intawaroroj Rd, Chiang Mai 50200, Thailand.
[Jourdain, Gonzague; Ngo-Giang-Huong, Nicole; Cressey, Tim R.] Harvard TH Chan Sch Publ Hlth, Dept Immunol & Infect Dis, 677 Huntington Ave, Boston, MA 02115 USA.
[Cressey, Tim R.] Univ Liverpool, Inst Translat Med, Dept Mol & Clin Pharmacol, Liverpool, Merseyside, England.
[Hua, Lei; Harrison, Linda; Tierney, Camlin] Harvard TH Chan Sch Publ Hlth, Ctr Biostat AIDS Res CBAR, 677 Huntington Ave, Boston, MA 02115 USA.
[Bowonwatanuwong, Chureeratana; Chotivanich, Nantasak] Chonburi Hosp, 69 M-2,Sukhumvit Rd, Muang 20000, Chonburi, Thailand.
[Puthanakit, Thanyawee] Chulalongkorn Univ, Fac Med, 1873 Rama 4 Rd, Bangkok 10330, Thailand.
[Siberry, George K.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, 6100 Execut Blvd, Bethesda, MD 20892 USA.
[Watts, Diane Heather] US Dept State, Off Global AIDS Coordinator, SA-22,2201 C St NW, Washington, DC 20522 USA.
[Murphy, Trudy V.] Ctr Dis Control & Prevent, DHHS CDC NCHHSTP DVH Vaccine Unit, Bldg Corp SQ 12,Room 3111, Atlanta, GA 30329 USA.
[Achalapong, Jullapong] Chiangrai Prachanukroh Hosp, Dept Obstet & Gynecol, 1039 Sathan Phayaban Rd, Muang 57000, Chiang Rai, Thailand.
[Hongsiriwon, Suchat] Chonburi Hosp, Dept Pediat, 69 M-2,Sukhumvit Rd, Muang 20000, Chonburi, Thailand.
[Klinbuayaem, Virat] Sanpatong Hosp, Dept Med, 149 M-15 Yuhwa, Chiang Mai 50120, Thailand.
[Traisathit, Patrinee] Chiang Mai Univ, Dept Stat, Fac Sci, 239 Huaykaew Rd, Chiang Mai 50200, Thailand.
[Thongsawat, Satawat] Chiang Mai Univ, Dept Internal Med, Fac Med, Chiang Mai 50200, Thailand.
[Chung, Raymond T.] Massachusetts Gen Hosp, Gastrointestinal Unit, GI Unit, WRN 1007C,55 Fruit St, Boston, MA 02114 USA.
[Pol, Stanislas] Cochin Univ Hosp, Dept Hepatogastroenterol, 27 Rue Faubourg St Jacques, F-75679 Paris 14, France.
RP Jourdain, G (reprint author), Inst Rech Dev IRD France, PHPT, UMI 174, 187-10 Changklan Rd, Chiang Mai 50100, Thailand.; Jourdain, G (reprint author), Chiang Mai Univ, Fac Associated Med Sci, 110 Intawaroroj Rd, Chiang Mai 50200, Thailand.
EM gonzague.jourdain@ird.fr
FU Eunice Kennedy Shriver National Institute of Child Health & Human
Development (NICHD) [U01HD071889]
FX The study activities are supported by a grant from the Eunice Kennedy
Shriver National Institute of Child Health & Human Development (NICHD)
(U01HD071889) under a cooperative agreement between NICHD, the Centers
for Disease Control and Prevention, United States of America, and
Institut de recherche pour le developpement, France.
NR 12
TC 1
Z9 1
U1 8
U2 8
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 AUG 9
PY 2016
VL 16
AR 393
DI 10.1186/s12879-016-1734-5
PG 6
WC Infectious Diseases
SC Infectious Diseases
GA DT2YM
UT WOS:000381347700010
PM 27506549
ER
PT J
AU Ordonez, AE
Ranney, R
Schwartz, M
Mathews, CA
Satre, DD
AF Ordonez, Anna E.
Ranney, Rachel
Schwartz, Maxine
Mathews, Carol A.
Satre, Derek D.
TI Hazardous drinking among young adults seeking outpatient mental health
services
SO Addiction Science & Clinical Practice
LA English
DT Article
DE Alcohol; Hazardous drinking; Cannabis; Depression; Mental health; Young
adults
ID ALCOHOL-USE DISORDERS; RANDOMIZED CONTROLLED-TRIAL; SUBSTANCE USE
DISORDER; NATIONAL EPIDEMIOLOGIC SURVEY; DRUG-USE; PSYCHIATRIC-SERVICES;
BRIEF INTERVENTION; COMORBIDITY; CONSUMPTION; PREVALENCE
AB Background: Alcohol use can have a significant negative impact on young adults in mental health treatment. This cross-sectional study examined prevalence and factors associated with hazardous drinking among young adults seeking outpatient mental health services, rate of alcohol use disorders (AUDs), and the relationship between hazardous drinking and other types of substance use.
Methods: Participants were 487 young adults ages 18-25 who completed self-administered computerized screening questions for alcohol and drug use. Alcohol use patterns were assessed and predictors of hazardous drinking (>= 5 drinks on one or more occasions in the past year) were identified using logistic regression.
Results: Of the 487 participants, 79.8 % endorsed prior-year alcohol use, 52.3 % reported one or more episodes of hazardous drinking in the prior year and 8.2 % were diagnosed with an AUD. Rates of recent and lifetime alcohol, tobacco and marijuana use were significantly greater in those with prior-year hazardous drinking. In logistic regression, prior-year hazardous drinking was associated with lifetime marijuana use (OR 3.30, p < 0.001; 95 % CI 2.05, 5.28), lifetime tobacco use (OR 1.88, p = 0.004; 95 % CI 1.22, 2.90) and older age (OR 1.18 per year, p < 0.001; 95 % CI 1.08, 1.29).
Conclusions: In an outpatient mental health setting, high rates of hazardous drinking were identified, and drinking was associated with history of other substance use. Results highlight patient characteristics associated with hazardous drinking that mental health providers should be aware of in treating young adults, especially older age and greater use of tobacco and marijuana.
C1 [Ordonez, Anna E.; Ranney, Rachel; Schwartz, Maxine; Mathews, Carol A.; Satre, Derek D.] Univ Calif San Francisco, Dept Psychiat, 401 Parnassus Ave, San Francisco, CA 94143 USA.
[Ordonez, Anna E.; Ranney, Rachel; Schwartz, Maxine; Mathews, Carol A.; Satre, Derek D.] Univ Calif San Francisco, UCSF Weill Inst Neurosci, 401 Parnassus Ave, San Francisco, CA 94143 USA.
[Satre, Derek D.] Kaiser Permanente Northern Calif Reg, Div Res, 2000 Broadway,3rd Floor, Oakland, CA 94612 USA.
[Ordonez, Anna E.] NIMH, Off Clin Res, 6001 Execut Blvd MSC 9669, Bethesda, MD 20892 USA.
[Mathews, Carol A.] Univ Florida, Dept Psychiat, 100 S Newell Dr, Gainesville, FL 32610 USA.
RP Ordonez, AE (reprint author), Univ Calif San Francisco, Dept Psychiat, 401 Parnassus Ave, San Francisco, CA 94143 USA.; Ordonez, AE (reprint author), Univ Calif San Francisco, UCSF Weill Inst Neurosci, 401 Parnassus Ave, San Francisco, CA 94143 USA.; Ordonez, AE (reprint author), NIMH, Off Clin Res, 6001 Execut Blvd MSC 9669, Bethesda, MD 20892 USA.
EM anna.ordonez@nih.gov
FU NIAAA NIH HHS [R01 AA020463]; NIDA NIH HHS [T32 DA007250]; NIMH NIH HHS
[R25 MH060482]
NR 30
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 1940-0640
J9 ADDICT SCI CLIN PRAC
JI Addict. Sci. Clin. Pract.
PD AUG 9
PY 2016
VL 11
AR 12
DI 10.1186/s13722-016-0060-y
PG 7
WC Substance Abuse
SC Substance Abuse
GA DS9RR
UT WOS:000381121500001
PM 27506832
ER
PT J
AU Gach, JS
Gorlani, A
Dotsey, EY
Becerra, JC
Anderson, CTM
Berzins, B
Felgner, PL
Forthal, DN
Deeks, SG
Wilkin, TJ
Casazza, JP
Koup, RA
Katlama, C
Autran, B
Murphy, RL
Achenbach, CJ
AF Gach, Johannes S.
Gorlani, Andrea
Dotsey, Emmanuel Y.
Becerra, Juan C.
Anderson, Chase T. M.
Berzins, Baiba
Felgner, Philip L.
Forthal, Donald N.
Deeks, Steven G.
Wilkin, Timothy J.
Casazza, Joseph P.
Koup, Richard A.
Katlama, Christine
Autran, Brigitte
Murphy, Robert L.
Achenbach, Chad J.
TI HIV-1-Specific Antibody Response and Function after DNA Prime and
Recombinant Adenovirus 5 Boost HIV Vaccine in HIV-Infected Subjects
SO PLOS ONE
LA English
DT Article
ID DEPENDENT CELLULAR CYTOTOXICITY; IMMUNODEFICIENCY-VIRUS TYPE-1;
NEUTRALIZING ANTIBODIES; MONOCLONAL-ANTIBODY; EFFICACY TRIAL;
ANTIRETROVIRAL THERAPY; MEDIATED CYTOTOXICITY; LONGITUDINAL ANALYSIS;
ENVELOPE PROTEINS; EPITOPES
AB Little is known about the humoral immune response against DNA prime-recombinant adenovirus 5 (rAd5) boost HIV vaccine among HIV-infected patients on long-term suppressive antiretroviral therapy (ART). Previous studies emphasized cellular immune responses; however, current research suggests both cellular and humoral responses are likely required for a successful therapeutic vaccine. Thus, we aimed to understand antibody response and function induced by vaccination of ART-treated HIV-1-infected patients with immune recovery. All subjects participated in EraMune 02, an open-label randomized clinical trial of ART intensification followed by a six plasmid DNA prime (envA, envB, envC, gagB, polB, nefB) and rAd5 boost HIV vaccine with matching inserts. Antibody binding levels were determined with a recently developed microarray approach. We also analyzed neutralization efficiency and antibody-dependent cellular cytotoxicity (ADCC). We found that the DNA prime-rAd5 boost vaccine induced a significant cross-clade HIV-specific antibody response, which correlated with antibody neutralization efficiency. However, despite the increase in antibody binding levels, the vaccine did not significantly stimulate neutralization or ADCC responses. This finding was also reflected by a lack of change in total CD4+ cell associated HIV DNA in those who received the vaccine. Our results have important implications for further therapeutic vaccine design and administration, especially in HIV-1 infected patients, as boosting of preexisting antibody responses are unlikely to lead to clearance of latent proviruses in the HIV reservoir.
C1 [Gach, Johannes S.; Gorlani, Andrea; Dotsey, Emmanuel Y.; Becerra, Juan C.; Felgner, Philip L.; Forthal, Donald N.] Univ Calif Irvine, Dept Med, Div Infect Dis, Irvine, CA 92717 USA.
[Anderson, Chase T. M.; Berzins, Baiba; Murphy, Robert L.; Achenbach, Chad J.] Northwestern Univ, Dept Med, Feinberg Sch Med, Div Infect Dis,Ctr Global Hlth, Chicago, IL 60611 USA.
[Deeks, Steven G.] San Francisco Gen Hosp, Div HIV AIDS, San Francisco, CA 94110 USA.
[Deeks, Steven G.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Wilkin, Timothy J.] Weill Cornell Med Coll, Div Infect Dis, New York, NY USA.
[Casazza, Joseph P.; Koup, Richard A.] NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Katlama, Christine] Hop La Pitie Salpetriere, Dept Infect Dis, Paris, France.
[Autran, Brigitte] Hop La Pitie Salpetriere, Dept Immunol, Paris, France.
[Gorlani, Andrea] ModiQuest Res, Oss, Netherlands.
RP Gach, JS (reprint author), Univ Calif Irvine, Dept Med, Div Infect Dis, Irvine, CA 92717 USA.; Achenbach, CJ (reprint author), Northwestern Univ, Dept Med, Feinberg Sch Med, Div Infect Dis,Ctr Global Hlth, Chicago, IL 60611 USA.
EM jgach@uci.edu; c-achenbach@northwestern.edu
OI Gach, Johannes/0000-0002-5043-5710
FU Objectif Recherche Vaccin SIDA (ORVACS)
FX Objectif Recherche Vaccin SIDA (ORVACS) provided all funding for this
study. The funders had no role in study design, data collection and
analysis, decision to publish, or preparation of the manuscript.
NR 56
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 AUG 8
PY 2016
VL 11
IS 8
AR e0160341
DI 10.1371/journal.pone.0160341
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DT3IE
UT WOS:000381373500020
PM 27500639
ER
PT J
AU Hong, CS
Singh, LN
Mullikin, JC
Biesecker, LG
AF Hong, Celine S.
Singh, Larry N.
Mullikin, James C.
Biesecker, Leslie G.
TI Assessing the reproducibility of exome copy number variations
predictions
SO GENOME MEDICINE
LA English
DT Article
DE Copy number variations (CNV); Exomes; CNV predictions; Reproducibility
ID SEQUENCING DATA; DISCOVERY; VARIANTS; TOOLS; DEPTH
AB Background: Reproducibility is receiving increased attention across many domains of science and genomics is no exception. Efforts to identify copy number variations (CNVs) from exome sequence (ES) data have been increasing. Many algorithms have been published to discover CNVs from exomes and a major challenge is the reproducibility in other datasets. Here we test exome CNV calling reproducibility under three conditions: data generated by different sequencing centers; varying sample sizes; and varying capture methodology.
Methods: Four CNV tools were tested: eXome Hidden Markov Model (XHMM), Copy Number Inference From Exome Reads (CoNIFER), EXCAVATOR, and Copy Number Analysis for Targeted Resequencing (CONTRA). To examine the reproducibility, we ran the callers on four datasets, varying sample sizes of N = 10, 30, 75, 100, 300, and data with different capture methodology. We examined the false negative (FN) calls and false positive (FP) calls for potential limitations of the CNV callers. The positive predictive value (PPV) was measured by checking the CNV call concordance against single nucleotide polymorphism array.
Results: Using independently generated datasets, we examined the PPV for each dataset and observed wide range of PPVs. The PPV values were highly data dependent (p < 0.001). For the sample sizes and capture method analyses, we tested the callers in triplicates. Both analyses resulted in wide ranges of PPVs, even for the same test. Interestingly, negative correlations between the PPV and the sample sizes were observed for CoNIFER (rho = - 0.80). Further examination of FN calls showed that 44 % of these were missed by all callers and were attributed to the CNV size (46 % spanned = 3 exons). Overlap of the FP calls showed that FPs were unique to each caller, indicative of algorithm dependency.
Conclusions: Our results demonstrate that further improvements in CNV callers are necessary to improve reproducibility and to include wider spectrum of CNVs (including the small CNVs). These CNV callers should be evaluated on multiple independent, heterogeneously generated datasets of varying size to increase robustness and utility. These approaches to the evaluation of exome CNV are essential to support wide utility and applicability of CNV discovery in exome studies.
C1 [Hong, Celine S.; Singh, Larry N.; Biesecker, Leslie G.] NHGRI, Med Genom & Metab Genet Branch, NIH, Bethesda, MD 20892 USA.
[Mullikin, James C.; Biesecker, Leslie G.] NHGRI, NIH Intramural Sequencing Ctr, NIH, Bethesda, MD 20852 USA.
[Mullikin, James C.] NHGRI, Comparat Genom Anal Unit, Canc Genet & Comparat Genom Branch, NIH, Bethesda, MD 20852 USA.
RP Biesecker, LG (reprint author), NHGRI, Med Genom & Metab Genet Branch, NIH, Bethesda, MD 20892 USA.; Biesecker, LG (reprint author), NHGRI, NIH Intramural Sequencing Ctr, NIH, Bethesda, MD 20852 USA.
EM lesb@mail.nih.gov
FU Intramural Research Program of the National Human Genome Research
Institute, National Institutes of Health
FX This work was supported by the Intramural Research Program of the
National Human Genome Research Institute, National Institutes of Health.
NR 28
TC 1
Z9 1
U1 3
U2 3
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 AUG 8
PY 2016
VL 8
AR 82
DI 10.1186/s13073-016-0336-6
PG 11
WC Genetics & Heredity
SC Genetics & Heredity
GA DT2XL
UT WOS:000381345000001
PM 27503473
ER
PT J
AU Elwyn, G
Frosch, DL
Kobrin, S
AF Elwyn, Glyn
Frosch, Dominick L.
Kobrin, Sarah
TI Implementing shared decision-making: consider all the consequences
SO IMPLEMENTATION SCIENCE
LA English
DT Article
DE Collaborative deliberation; Shared decision making; Patient-centered
care; Implementation; Practice improvement; Quality improvement;
Multilevel; Conceptual model; Measurement
ID SUPPORT INTERVENTIONS; HEALTH-CARE; MULTILEVEL FACTORS;
CLINICAL-PRACTICE; PATIENT; AIDS; SATISFACTION; METAANALYSIS; ADHERENCE;
OUTCOMES
AB Background: The ethical argument that shared decision-making is "the right" thing to do, however laudable, is unlikely to change how healthcare is organized, just as evidence alone will be an insufficient factor: practice change is governed by factors such as cost, profit margin, quality, and efficiency. It is helpful, therefore, when evaluating new approaches such as shared decision-making to conceptualize potential consequences in a way that is broad, long-term, and as relevant as possible to multiple stakeholders. Yet, so far, evaluation metrics for shared decision-making have been mostly focused on short-term outcomes, such as cognitive or affective consequences in patients. The goal of this article is to hypothesize a wider set of consequences, that apply over an extended time horizon, and include outcomes at interactional, team, organizational and system levels, and to call for future research to study these possible consequences.
Main argument: To date, many more studies have evaluated patient decision aids rather than other approaches to shared decision-making, and the outcomes measured have typically been focused on short-term cognitive and affective outcomes, for example knowledge and decisional conflict. From a clinicians perspective, the shared decision-making process could be viewed as either intrinsically rewarding and protective, or burdensome and impractical, yet studies have not focused on the impact on professionals, either positive or negative. At interactional levels, group, team, and microsystem, the potential long-term consequences could include the development of a culture where deliberation and collaboration are regarded as guiding principles, where patients are coached to assess the value of interventions, to trade-off benefits versus harms, and assess their burdens-in short, to new social norms in the clinical workplace. At organizational levels, consistent shared decision-making might boost patient experience evaluations and lead to fewer complaints and legal challenges. In the long-term, shared decision-making might lead to changes in resource utilization, perhaps to reductions in cost, and to modification of workforce composition. Despite the gradual shift to value-based payment, some organizations, motivated by continued income derived from achieving high volumes of procedures and contacts, will see this as a negative consequence.
Conclusion: We suggest that a broader conceptualization and measurement of shared decision-making would provide a more substantive evidence base to guide implementation. We outline a framework which illustrates a hypothesized set of proximal, distal, and distant consequences that might occur if collaboration and deliberation could be achieved routinely, proposing that well-informed preference- based patient decisions might lead to safer, more cost-effective healthcare, which in turn might result in reduced utilization rates and improved health outcomes.
C1 [Elwyn, Glyn] Dartmouth Inst Hlth Policy & Clin Practice, 37 Dewey Field Rd, Hanover, NH 03755 USA.
[Frosch, Dominick L.] Palo Alto Med Fdn, Res Inst, 795 El Camino Real, Palo Alto, CA 94301 USA.
[Frosch, Dominick L.] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA.
[Kobrin, Sarah] NCI, 9609 Med Ctr Dr, Rockville, MD 20850 USA.
RP Elwyn, G (reprint author), Dartmouth Inst Hlth Policy & Clin Practice, 37 Dewey Field Rd, Hanover, NH 03755 USA.
EM glynelwyn@gmail.com
NR 45
TC 3
Z9 3
U1 12
U2 18
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1748-5908
J9 IMPLEMENT SCI
JI Implement. Sci.
PD AUG 8
PY 2016
VL 11
AR 114
DI 10.1186/s13012-016-0480-9
PG 10
WC Health Care Sciences & Services; Health Policy & Services
SC Health Care Sciences & Services
GA DT7KJ
UT WOS:000381665200002
PM 27502770
ER
PT J
AU Bissinger, R
Lang, E
Ghashghaeinia, M
Singh, Y
Zelenak, C
Fehrenbacher, B
Honisch, S
Chen, H
Fakhri, H
Umbach, AT
Liu, GL
Rexhepaj, R
Liu, GX
Schaller, M
Mack, AF
Lupescu, A
Birnbaumer, L
Lang, F
Qadri, SM
AF Bissinger, Rosi
Lang, Elisabeth
Ghashghaeinia, Mehrdad
Singh, Yogesh
Zelenak, Christine
Fehrenbacher, Birgit
Honisch, Sabina
Chen, Hong
Fakhri, Hajar
Umbach, Anja T.
Liu, Guilai
Rexhepaj, Rexhep
Liu, Guoxing
Schaller, Martin
Mack, Andreas F.
Lupescu, Adrian
Birnbaumer, Lutz
Lang, Florian
Qadri, Syed M.
TI Blunted apoptosis of erythrocytes in mice deficient in the
heterotrimeric G-protein subunit G alpha i2
SO SCIENTIFIC REPORTS
LA English
DT Article
ID IN-VITRO; SIGNAL-TRANSDUCTION; OXIDATIVE STRESS; SUICIDAL DEATH;
CELL-DEATH; RED-CELLS; ACTIVATION; ERYPTOSIS; STIMULATION; SURVIVAL
AB Putative functions of the heterotrimeric G-protein subunit G alpha i2-dependent signaling include ion channel regulation, cell differentiation, proliferation and apoptosis. Erythrocytes may, similar to apoptosis of nucleated cells, undergo eryptosis, characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine (PS) exposure. Eryptosis may be triggered by increased cytosolic Ca2+ activity and ceramide. In the present study, we show that G alpha i2 is expressed in both murine and human erythrocytes and further examined the survival of erythrocytes drawn from G alpha i2-deficient mice (G alpha i2(-/-)) and corresponding wild-type mice (G alpha i(2+/+)). Our data show that plasma erythropoietin levels, erythrocyte maturation markers, erythrocyte counts, hematocrit and hemoglobin concentration were similar in G alpha i2(-/-) and G alpha i(2+/+) mice but the mean corpuscular volume was significantly larger in G alpha i2(-/-) mice. Spontaneous PS exposure of circulating G alpha i2(-/-) erythrocytes was significantly lower than that of circulating G alpha i(2+/+) erythrocytes. PS exposure was significantly lower in G alpha i2(-/-) than in G alpha i(2+/+) erythrocytes following ex vivo exposure to hyperosmotic shock, bacterial sphingomyelinase or C6 ceramide. Erythrocyte G alpha i2 deficiency further attenuated hyperosmotic shock-induced increase of cytosolic Ca2+ activity and cell shrinkage. Moreover, G alpha i2(-/-) erythrocytes were more resistant to osmosensitive hemolysis as compared to G alpha i(2+/+) erythrocytes. In conclusion, G alpha i2 deficiency in erythrocytes confers partial protection against suicidal cell death.
C1 [Bissinger, Rosi; Ghashghaeinia, Mehrdad; Singh, Yogesh; Honisch, Sabina; Chen, Hong; Fakhri, Hajar; Umbach, Anja T.; Liu, Guilai; Rexhepaj, Rexhep; Liu, Guoxing; Lupescu, Adrian; Lang, Florian; Qadri, Syed M.] Univ Tubingen, Inst Cardiol Vasc Med & Physiol, Tubingen, Germany.
[Lang, Elisabeth] Univ Duesseldorf, Dept Gastroenterol Hepatol & Infect Dis, Dusseldorf, Germany.
[Zelenak, Christine] Charite, Dept Internal Med, Berlin, Germany.
[Fehrenbacher, Birgit; Schaller, Martin] Univ Tubingen, Dept Dermatol, Tubingen, Germany.
[Rexhepaj, Rexhep] Univ Bonn, Inst Biochem & Mol Biol, Bonn, Germany.
[Mack, Andreas F.] Univ Tubingen, Inst Anat, Tubingen, Germany.
[Birnbaumer, Lutz] NIEHS, Neurobiol Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.
[Qadri, Syed M.] Catholic Univ Argentina, Sch Med Sci, Inst Biomed Res BIOMED, Buenos Aires, DF, Argentina.
[Qadri, Syed M.] McMaster Univ, Dept Pathol & Mol Med, Hamilton, ON, Canada.
RP Lang, F (reprint author), Univ Tubingen, Inst Cardiol Vasc Med & Physiol, Tubingen, Germany.
EM florian.lang@uni-tuebingen.de
FU Deutsche Forschungsgemeinschaft [La 315/13-3]; NIH [Z01-ES-101643]
FX The authors thank Prof. Bernd Nurnberg and members of his laboratory
(Institute of Experimental and Clinical Pharmacology and Toxicology,
University of Tubingen, Germany) for their valuable suggestions and for
providing blood from G alpha i2-/- mice. The authors
acknowledge the meticulous preparation of the manuscript by Tanja Loch
and the technical assistance of Efi Faber and Annette Knoblich. This
study was supported by Deutsche Forschungsgemeinschaft (Nr. La 315/13-3)
and the Intramural Research Program of the NIH (project Z01-ES-101643 to
LB).
NR 60
TC 1
Z9 1
U1 5
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 AUG 8
PY 2016
VL 6
AR 30925
DI 10.1038/srep30925
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DT4NF
UT WOS:000381457200001
PM 27499046
ER
PT J
AU Hirschman, L
Fort, K
Boue, S
Kyrpides, N
Dogan, RI
Cohen, KB
AF Hirschman, Lynette
Fort, Karen
Boue, Stephanie
Kyrpides, Nikos
Dogan, Rezarta Islamaj
Cohen, Kevin Bretonnel
TI Crowdsourcing and curation: perspectives from biology and natural
language processing
SO DATABASE-THE JOURNAL OF BIOLOGICAL DATABASES AND CURATION
LA English
DT Article
ID ANNOTATION; RETRIEVAL; NETWORKS; IMPROVER; GENE; TEXT
AB Crowdsourcing is increasingly utilized for performing tasks in both natural language processing and biocuration. Although there have been many applications of crowdsourcing in these fields, there have been fewer high-level discussions of the methodology and its applicability to biocuration. This paper explores crowdsourcing for biocura