FN Thomson Reuters Web of Science™
VR 1.0
PT J
AU Hanson, ML
Hixon, JA
Li, W
Felber, BK
Anver, MR
Stewart, CA
Shen, W
Steidler, L
Durum, SK
AF Hanson, M. L.
Hixon, J. A.
Li, W.
Felber, B. K.
Anver, M. R.
Stewart, C. A.
Shen, W.
Steidler, L.
Durum, S. K.
TI LACTOCOCCUS LACTIS EXPRESSING IL-27: A POTENTIAL THERAPEUTIC FOR
INFLAMMATORY BOWEL DISEASE
SO INFLAMMATION RESEARCH
LA English
DT Meeting Abstract
CT 17th International Conference of the Inflammation-Research-Association
CY SEP 09-13, 2012
CL Bolton Landing, NY
SP Inflammat Res Assoc
C1 [Hanson, M. L.; Hixon, J. A.; Li, W.; Felber, B. K.; Anver, M. R.; Stewart, C. A.; Shen, W.; Durum, S. K.] NCI, Ctr Canc Res, Frederick, MD 21701 USA.
[Steidler, L.] ActoGenix NV, Zwijnaarde, Belgium.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU SPRINGER BASEL AG
PI BASEL
PA PICASSOPLATZ 4, BASEL, 4052, SWITZERLAND
SN 1023-3830
J9 INFLAMM RES
JI Inflamm. Res.
PD SEP
PY 2012
VL 61
SU 1
BP S15
EP S16
PG 2
WC Cell Biology; Immunology
SC Cell Biology; Immunology
GA 998FT
UT WOS:000308223600022
ER
PT J
AU Khatami, M
AF Khatami, Mahin
TI UNRESOLVED INFLAMMATION: 'IMMUNE TSUNAMI' AND CANCER CACHEXIA INDUCED BY
"TARGETED" THERAPIES
SO INFLAMMATION RESEARCH
LA English
DT Meeting Abstract
CT 17th International Conference of the Inflammation-Research-Association
CY SEP 09-13, 2012
CL Bolton Landing, NY
SP Inflammat Res Assoc
C1 [Khatami, Mahin] NCI, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER BASEL AG
PI BASEL
PA PICASSOPLATZ 4, BASEL, 4052, SWITZERLAND
SN 1023-3830
J9 INFLAMM RES
JI Inflamm. Res.
PD SEP
PY 2012
VL 61
SU 1
BP S17
EP S18
PG 2
WC Cell Biology; Immunology
SC Cell Biology; Immunology
GA 998FT
UT WOS:000308223600026
ER
PT J
AU Yan, HH
Pang, YL
Yang, L
AF Yan, Hannah H.
Pang, Yanli
Yang, Li
TI CCL9 MEDIATES TGF-beta REGULATION OF TUMOR CELL SURVIVAL AND LUNG
METASTASIS
SO INFLAMMATION RESEARCH
LA English
DT Meeting Abstract
CT 17th International Conference of the Inflammation-Research-Association
CY SEP 09-13, 2012
CL Bolton Landing, NY
SP Inflammat Res Assoc
C1 [Yan, Hannah H.; Pang, Yanli; Yang, Li] NCI, Lab Canc Biol & Genet, NIH, Bethesda, MD 21892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER BASEL AG
PI BASEL
PA PICASSOPLATZ 4, BASEL, 4052, SWITZERLAND
SN 1023-3830
J9 INFLAMM RES
JI Inflamm. Res.
PD SEP
PY 2012
VL 61
SU 1
BP S28
EP S28
PG 1
WC Cell Biology; Immunology
SC Cell Biology; Immunology
GA 998FT
UT WOS:000308223600054
ER
PT J
AU Tolea, MI
Terracciano, A
Milaneschi, Y
Metter, EJ
Ferrucci, L
AF Tolea, Magdalena I.
Terracciano, Antonio
Milaneschi, Yuri
Metter, E. Jeffrey
Ferrucci, Luigi
TI Personality Typology in Relation to Muscle Strength
SO INTERNATIONAL JOURNAL OF BEHAVIORAL MEDICINE
LA English
DT Article
DE Personality; Muscle strength; Physical activity; Cross-sectional studies
ID OLDER-ADULTS; PRIMARY-CARE; PHYSICAL-ACTIVITY; PERCEIVED HEALTH;
5-FACTOR MODEL; AGE; TRAITS; MEN; DISABILITY; WOMEN
AB Physical inactivity plays a central role in the age-related decline in muscle strength, an important component in the process leading to disability. Personality, a significant determinant of health behaviors including physical activity, could therefore impact muscle strength throughout adulthood and affect the rate of muscle strength decline with aging. Personality typologies combining "high neuroticism" (N a parts per thousand yenaEuro parts per thousand 55), "low extraversion" (E < 45), and "low conscientiousness" (C < 45) have been associated with multiple risky health behaviors but have not been investigated with regards to muscle strength.
The purpose of this study is to investigate associations between individual and combined typologies consisting of high N, low E, and low C and muscle strength, and whether physical activity and body mass index act as mediators.
This cross-sectional study includes 1,220 participants from the Baltimore Longitudinal Study of Aging.
High N was found among 18%, low E among 31%, and low C among 26% of the sample. High levels of N, particularly when combined with either low E or low C, were associated with lower muscle strength compared with having only one or none of these personality types. Facet analyses suggest an important role for the N components of depression and hostility. Physical activity level appears to partly explain some of these associations.
Findings provide support for the notion that the typological approach to personality may be useful in identifying specific personality types at risk of low muscle strength and offer the possibility for more targeted prevention and intervention programs.
C1 [Tolea, Magdalena I.; Milaneschi, Yuri; Metter, E. Jeffrey; Ferrucci, Luigi] Natl Inst Aging, Clin Res Branch, Longitudinal Studies Sect, Baltimore, MD 21225 USA.
[Terracciano, Antonio] Natl Inst Aging, Intramural Res Program, Lab Personal & Cognit, Baltimore, MD USA.
RP Tolea, MI (reprint author), Natl Inst Aging, Clin Res Branch, Longitudinal Studies Sect, 3001 S Hanover St,5th Floor, Baltimore, MD 21225 USA.
EM toleam@mail.nih.gov
RI terracciano, antonio/B-1884-2008
FU Intramural NIH HHS [ZIA AG000197-04, Z99 AG999999, ZIA AG000183-22, ZIA
AG000183-23, ZIA AG000197-03]; NIA NIH HHS [Z01 AG000015-50]
NR 47
TC 4
Z9 4
U1 2
U2 7
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1070-5503
J9 INT J BEHAV MED
JI Int. J. Behav. Med.
PD SEP
PY 2012
VL 19
IS 3
BP 382
EP 390
DI 10.1007/s12529-011-9166-5
PG 9
WC Psychology, Clinical
SC Psychology
GA 992CT
UT WOS:000307753800016
PM 21614452
ER
PT J
AU Teresi, JA
Stewart, AL
Stahl, SM
AF Teresi, Jeanne A.
Stewart, Anita L.
Stahl, Sidney M.
TI Fifteen Years of Progress in Measurement and Methods at the Resource
Centers for Minority Aging Research
SO JOURNAL OF AGING AND HEALTH
LA English
DT Article
C1 [Teresi, Jeanne A.] Columbia Univ, Stroud Ctr, Hebrew Home, NY USA.
[Teresi, Jeanne A.] Columbia Univ, Div Res, Hebrew Home, NY USA.
[Stewart, Anita L.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Stahl, Sidney M.] NIA, Individual Behav Proc Branch, Div Behav & Social Res, NIH, Bethesda, MD 20892 USA.
RP Teresi, JA (reprint author), Columbia Univ, Stroud Ctr, Fac Med, 5901 Palisade Ave, Riverdale, NY USA.
EM jat61@columbia.edu
FU NIA NIH HHS [P30 AG 15292, P30 AG 31054, P30 AG015294, P30 AG 21677, P30
AG 31043, P30 AG 15272, P30 AG 21684, P30 AG 15272-12S2, P30 AG 15294,
P30 AG 15281]; NIMHD NIH HHS [P60 MD00206, P60 MD000206]
NR 9
TC 2
Z9 2
U1 2
U2 5
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0898-2643
J9 J AGING HEALTH
JI J. Aging Health
PD SEP
PY 2012
VL 24
IS 6
BP 985
EP 991
DI 10.1177/0898264312457750
PG 7
WC Gerontology; Health Policy & Services
SC Geriatrics & Gerontology; Health Care Sciences & Services
GA 990NY
UT WOS:000307638900004
PM 22904184
ER
PT J
AU Bornstein, MH
Hendricks, C
AF Bornstein, Marc H.
Hendricks, Charlene
TI Basic language comprehension and production in > 100,000 young children
from sixteen developing nations
SO JOURNAL OF CHILD LANGUAGE
LA English
DT Article
ID VOCABULARY COMPETENCE; LEXICAL DEVELOPMENT; ACQUISITION; SUPPORT; INPUT;
RISK
AB Using the Multiple Indicator Cluster Survey, language comprehension and production were compared in a sample of 101,250 children aged 2; 00 to 9; 11 and a focus subsample of 38,845 children aged 2; 00 to 4; 11 from sixteen under-researched developing nations. In the whole sample, comprehension slightly exceeded production; correlations between comprehension and production by country were positive and significant, but varied in size, and the average correlation was positive, significant, and small to medium. Mean comprehension and production varied with child age, reaching an asymptote at 5; 00, and correlations between comprehension and production by age were positive, significant, and similar at each age. In the focus subsample, comprehension exceeded production; correlations between comprehension and production by country were positive and significant, but varied in size, and the average correlation was positive, significant, and medium in size. Children in countries with lower standards of living were less likely to demonstrate basic language comprehension or production.
C1 [Bornstein, Marc H.; Hendricks, Charlene] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD 20892 USA.
RP Bornstein, MH (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Suite 8030,6705 Rockledge Dr, Bethesda, MD 20892 USA.
EM Marc_H_Bornstein@nih.gov
FU Intramural NIH HHS [Z99 HD999999]
NR 40
TC 7
Z9 8
U1 1
U2 9
PU CAMBRIDGE UNIV PRESS
PI NEW YORK
PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA
SN 0305-0009
J9 J CHILD LANG
JI J. Child Lang.
PD SEP
PY 2012
VL 39
IS 4
BP 899
EP 918
DI 10.1017/S0305000911000407
PG 20
WC Psychology, Developmental; Linguistics; Psychology, Experimental
SC Psychology; Linguistics
GA 984IT
UT WOS:000307184000009
PM 22129486
ER
PT J
AU Cousins, MM
Ou, SS
Wawer, MJ
Munshaw, S
Swan, D
Magaret, CA
Mullis, CE
Serwadda, D
Porcella, SF
Gray, RH
Quinn, TC
Donnell, D
Eshleman, SH
Redd, AD
AF Cousins, Matthew M.
Ou, San-San
Wawer, Maria J.
Munshaw, Supriya
Swan, David
Magaret, Craig A.
Mullis, Caroline E.
Serwadda, David
Porcella, Stephen F.
Gray, Ronald H.
Quinn, Thomas C.
Donnell, Deborah
Eshleman, Susan H.
Redd, Andrew D.
TI Comparison of a High-Resolution Melting Assay to Next-Generation
Sequencing for Analysis of HIV Diversity
SO JOURNAL OF CLINICAL MICROBIOLOGY
LA English
DT Article
ID EVOLUTION; INFECTION; POPULATION; UGANDA; RAKAI; ENV; SUPERINFECTION;
SENSITIVITY; PROGRESSION; PREVENTION
AB Next-generation sequencing (NGS) has recently been used for analysis of HIV diversity, but this method is labor-intensive, costly, and requires complex protocols for data analysis. We compared diversity measures obtained using NGS data to those obtained using a diversity assay based on high-resolution melting (HRM) of DNA duplexes. The HRM diversity assay provides a single numeric score that reflects the level of diversity in the region analyzed. HIV gag and env from individuals in Rakai, Uganda, were analyzed in a previous study using NGS (n = 220 samples from 110 individuals). Three sequence-based diversity measures were calculated from the NGS sequence data (percent diversity, percent complexity, and Shannon entropy). The amplicon pools used for NGS were analyzed with the HRM diversity assay. HRM scores were significantly associated with sequence-based measures of HIV diversity for both gag and env (P < 0.001 for all measures). The level of diversity measured by the HRM diversity assay and NGS increased over time in both regions analyzed (P < 0.001 for all measures except for percent complexity in gag), and similar amounts of diversification were observed with both methods (P < 0.001 for all measures except for percent complexity in gag). Diversity measures obtained using the HRM diversity assay were significantly associated with those from NGS, and similar increases in diversity over time were detected by both methods. The HRM diversity assay is faster and less expensive than NGS, facilitating rapid analysis of large studies of HIV diversity and evolution.
C1 [Quinn, Thomas C.; Redd, Andrew D.] NIAID, Immunoregulat Lab, Div Intramural Res, NIH, Baltimore, MD USA.
[Cousins, Matthew M.; Eshleman, Susan H.] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA.
[Ou, San-San; Swan, David; Magaret, Craig A.; Donnell, Deborah] Fred Hutchinson Canc Res Ctr, Vaccine & Infect Dis Div, Seattle, WA 98104 USA.
[Wawer, Maria J.; Gray, Ronald H.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
[Munshaw, Supriya; Mullis, Caroline E.; Quinn, Thomas C.] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA.
[Serwadda, David] Makerere Univ, Sch Publ Hlth, Kampala, Uganda.
[Serwadda, David] Rakai Hlth Sci Program, Kalisizo, Uganda.
[Porcella, Stephen F.] NIAID, Genom Unit, Res Technol Sect, Rocky Mt Labs,Div Intramural Res,NIH, Hamilton, MT USA.
RP Redd, AD (reprint author), NIAID, Immunoregulat Lab, Div Intramural Res, NIH, Baltimore, MD USA.
EM aredd2@jhmi.edu
OI Donnell, Deborah/0000-0002-0587-7480
FU Bill and Melinda Gates Foundation [22006.03]; National Institutes of
Health (NIH), Division of Allergy and Infectious Diseases [U1AI51171,
1UO1AI075115-O1A1]; Department of the Army, U.S. Army Medical Research
and Materiel Command [DAMD17-98-2-8007]; Henry M. Jackson Foundation
[5D43TW00010]; HIV Prevention Trials Network (HPTN); NIAID, the National
Institute on Drug Abuse (NIDA), the National Institute of Mental Health;
Office of AIDS Research of the NIH and DHHS [U01AI068613, UM1AI068613];
NIAID [1R01-AI095068, UM1-AI068617]; Division of Intramural Research,
NIAID, NIH; Office of AIDS Research, NIH; Idaho Technology
FX We thank the participants and the study team of the Rakai Community
Cohort Study, which was supported by (i) the Bill and Melinda Gates
Foundation (22006.03), (ii) the National Institutes of Health (NIH),
Division of Allergy and Infectious Diseases (U1AI51171 and
1UO1AI075115-O1A1), (iii) the Department of the Army, U.S. Army Medical
Research and Materiel Command Cooperative Agreement (DAMD17-98-2-8007),
and (v) the Henry M. Jackson Foundation (5D43TW00010). This study was
supported by (i) the HIV Prevention Trials Network (HPTN) sponsored by
the NIAID, the National Institute on Drug Abuse (NIDA), the National
Institute of Mental Health, and the Office of AIDS Research of the NIH
and DHHS (U01AI068613 and UM1AI068613 to S. H. E.), (ii) NIAID
(1R01-AI095068 to S. H. E.), and (iii) NIAID (UM1-AI068617 to D. D.).
This study was supported in part by funding from the Division of
Intramural Research, NIAID, NIH, and the Office of AIDS Research, NIH.;
M.M.C. has given presentations at meetings sponsored by Idaho Technology
(marketer of the LightScanner platform and reagents designed
specifically for HRM analysis).
NR 33
TC 25
Z9 25
U1 1
U2 5
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0095-1137
J9 J CLIN MICROBIOL
JI J. Clin. Microbiol.
PD SEP
PY 2012
VL 50
IS 9
BP 3054
EP 3059
DI 10.1128/JCM.01460-12
PG 6
WC Microbiology
SC Microbiology
GA 994OZ
UT WOS:000307941900031
PM 22785188
ER
PT J
AU Winstona, J
Wolf, R
AF Winstona, Jason
Wolf, Ronald
TI Psoriasin (S100A7) promotes migration of a squamous carcinoma cell line
SO JOURNAL OF DERMATOLOGICAL SCIENCE
LA English
DT Letter
ID GLYCATION END-PRODUCTS; RAGE; RECEPTOR; INFLAMMATION
C1 [Winstona, Jason; Wolf, Ronald] NCI, Lab Canc Biol & Genet, Ctr Canc Res, Bethesda, MD 20892 USA.
[Wolf, Ronald] Univ Munich, Dept Dermatol, D-8000 Munich, Germany.
RP Wolf, R (reprint author), Dept Dermatol & Allergol, Frauenlobstr 9-11, D-80337 Munich, Germany.
EM ronald.wolf@med.uni-muenchen.de
FU Intramural NIH HHS
NR 12
TC 7
Z9 7
U1 0
U2 2
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0923-1811
J9 J DERMATOL SCI
JI J. Dermatol. Sci.
PD SEP
PY 2012
VL 67
IS 3
BP 205
EP 207
DI 10.1016/j.jdermsci.2012.06.009
PG 3
WC Dermatology
SC Dermatology
GA 990FK
UT WOS:000307616200011
PM 22795619
ER
PT J
AU Odgerel, Z
Lee, HS
Erdenebileg, N
Gandbold, S
Luvsanjamba, M
Sambuughin, N
Sonomtseren, S
Sharavdorj, P
Jodov, E
Altaisaikhan, K
Goldfarb, LG
AF Odgerel, Zagaa
Lee, Hee S.
Erdenebileg, Narnygerel
Gandbold, Suren
Luvsanjamba, Munkhjargal
Sambuughin, Nyamkhishig
Sonomtseren, Sainbileg
Sharavdorj, Purevdulam
Jodov, Erdenezul
Altaisaikhan, Khasag
Goldfarb, Lev G.
TI Genetic variants in potassium channels are associated with type 2
diabetes in a Mongolian population
SO JOURNAL OF DIABETES
LA English
DT Article
DE ABCC8; genetic association; KCNQ1; Mongolia; potassium channels; type 2
diabetes
ID SUBUNITS KIR6.2 KCNJ11; SULFONYLUREA RECEPTOR; SUSCEPTIBILITY LOCI;
MELLITUS; KCNQ1; MUTATIONS; DISEASES; ABCC8
AB Background: Recent genome-wide association studies (GWAS) have identified more than 40 common sequence variants associated with type 2 diabetes (T2D). However, the results are not always the same in populations with differing genetic backgrounds. In the present study, we evaluated a hypothesis that a North Asian population living in a geographic area with unusually harsh environmental conditions would develop unique genetic risks. Methods: A population-based association study was performed with 21 single-nucleotide polymorphisms (SNPs) in nine genes selected according to the results of GWAS conducted in other populations. The study participants included 393 full-heritage Mongolian individuals (177 diagnosed with T2D and 216 matched controls). Genotyping was performed by TaqMan methodology. Results: The strongest association was detected with SNPs located within the potassium channel-coding genes KCNQ1 (highest odds ratio [OR] = 1.92; P = 3.4 x 10-5) and ABCC8 (OR = 1.79; P = 5 x 10-4). Genetic variants identified as strongly influencing the risk of T2D in other populations (e.g. KCNJ11 or TCF7L2) did not show significant association in Mongolia. Conclusions: The strongest T2D risk-associated SNPs in Mongolians are located within two of three tested potassium channel-coding genes. Accumulated variations in these genes may be related to the exposure to harsh environmental conditions.
C1 [Odgerel, Zagaa; Lee, Hee S.; Goldfarb, Lev G.] NINDS, NIH, Bethesda, MD 20892 USA.
[Erdenebileg, Narnygerel] NIH, Infect Dis & Immunogenet Sect, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA.
[Gandbold, Suren] Natl Inst Forens Sci, Ulaanbaatar, Mongol Peo Rep.
[Luvsanjamba, Munkhjargal; Sharavdorj, Purevdulam] Minist Hlth, Ulaanbaatar, Mongol Peo Rep.
[Sambuughin, Nyamkhishig] Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA.
[Sonomtseren, Sainbileg; Jodov, Erdenezul; Altaisaikhan, Khasag] Hlth Sci Univ Mongolia, Ulaanbaatar, Mongol Peo Rep.
RP Goldfarb, LG (reprint author), NINDS, NIH, Room 4S06,5625 Fishers Lane, Bethesda, MD 20892 USA.
EM goldfarbl@ninds.nih.gov
FU National Institute of Neurological Disorders and Stroke, National
Institutes of Health
FX The authors thank the patients, their family members, and healthy
volunteers for participating in the study. This work was supported, in
part, by the Intramural Research Program of the National Institute of
Neurological Disorders and Stroke, National Institutes of Health.
NR 25
TC 8
Z9 9
U1 0
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1753-0393
J9 J DIABETES
JI J. Diabetes
PD SEP
PY 2012
VL 4
IS 3
BP 238
EP 242
DI 10.1111/j.1753-0407.2011.00177.x
PG 5
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 994LO
UT WOS:000307932500010
PM 22151254
ER
PT J
AU Zapka, J
Klabunde, CN
Taplin, S
Yuan, GG
Ransohoff, D
Kobrin, S
AF Zapka, Jane
Klabunde, Carrie N.
Taplin, Stephen
Yuan, Gigi
Ransohoff, David
Kobrin, Sarah
TI Screening Colonoscopy in the US: Attitudes and Practices of Primary Care
Physicians
SO JOURNAL OF GENERAL INTERNAL MEDICINE
LA English
DT Article
DE colorectal cancer screening; primary care physicians; colonoscopy
screening practices
ID SERVICES TASK-FORCE; COLORECTAL-CANCER; NATIONAL-SURVEY;
RECOMMENDATIONS; POPULATION; PREVENTION; BELIEFS; TRENDS
AB Rising colorectal cancer (CRC) screening rates in the last decade are attributable almost entirely to increased colonoscopy use. Little is known about factors driving the increase, but primary care physicians (PCPs) play a central role in CRC screening delivery.
Explore PCP attitudes toward screening colonoscopy and their associations with CRC screening practice patterns.
Cross-sectional analysis of data from a nationally representative survey conducted in 2006-2007.
1,266 family physicians, general practitioners, general internists, and obstetrician-gynecologists.
Physician-reported changes in the volume of screening tests ordered, performed or supervised in the past 3 years, attitudes toward colonoscopy, the influence of evidence and perceived norms on their recommendations, challenges to screening, and practice characteristics.
The cooperation rate (excludes physicians without valid contact information) was 75%; 28% reported their volume of FOBT ordering had increased substantially or somewhat, and the majority (53%) reported their sigmoidoscopy volume decreased either substantially or somewhat. A majority (73%) reported that colonoscopy volume increased somewhat or substantially. The majority (86%) strongly agreed that colonoscopy was the best of the available CRC screening tests; 69% thought it was readily available for their patients; 59% strongly or somewhat agreed that they might be sued if they did not offer colonoscopy to their patients. All three attitudes were significantly related to substantial increases in colonoscopy ordering.
PCPs report greatly increased colonoscopy recommendation relative to other screening tests, and highly favorable attitudes about colonoscopy. Greater emphasis is needed on informed decision-making with patients about preferences for test options.
C1 [Zapka, Jane] Med Univ S Carolina, Dept Med, Dept Biostat & Epidemiol, Charleston, SC 29425 USA.
[Klabunde, Carrie N.; Taplin, Stephen; Kobrin, Sarah] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Yuan, Gigi] Informat Management Serv Inc, Silver Spring, MD USA.
[Ransohoff, David] Univ N Carolina, Chapel Hill, NC USA.
RP Zapka, J (reprint author), Med Univ S Carolina, Dept Med, Dept Biostat & Epidemiol, 135 Cannon St, Charleston, SC 29425 USA.
EM zapka@musc.edu
FU National Cancer Institute [N02-PC-51308]; Agency for Healthcare Research
and Quality [Y3-PC-5019-01, Y3-PC-5019-02]; Centers for Disease Control
and Prevention [Y3-PC-6017-01]
FX Funding support for this study was provided by the National Cancer
Institute (contract no. N02-PC-51308); the Agency for Healthcare
Research and Quality (inter-agency agreement nos. Y3-PC-5019-01 and
Y3-PC-5019-02); and the Centers for Disease Control and Prevention
(inter-agency agreement no. Y3-PC-6017-01). The findings and conclusions
in this report are those of the authors and do not necessarily represent
the views or official position of the National Cancer Institute, the
Agency for Healthcare Research and Quality, or the Centers for Disease
Control and Prevention.
NR 40
TC 20
Z9 20
U1 0
U2 3
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0884-8734
J9 J GEN INTERN MED
JI J. Gen. Intern. Med.
PD SEP
PY 2012
VL 27
IS 9
BP 1150
EP 1158
DI 10.1007/s11606-012-2051-3
PG 9
WC Health Care Sciences & Services; Medicine, General & Internal
SC Health Care Sciences & Services; General & Internal Medicine
GA 988SP
UT WOS:000307511300014
PM 22539065
ER
PT J
AU Hernandez-Andrade, E
Romero, R
Ahn, H
Hussein, Y
Yeo, L
Korzeniewski, SJ
Chaiworapongsa, T
Hassan, SS
AF Hernandez-Andrade, Edgar
Romero, Roberto
Ahn, Hyunyoung
Hussein, Youssef
Yeo, Lami
Korzeniewski, Steven J.
Chaiworapongsa, Tinnakorn
Hassan, Sonia S.
TI Transabdominal evaluation of uterine cervical length during pregnancy
fails to identify a substantial number of women with a short cervix
SO JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE
LA English
DT Article
DE ultrasound; agreement; preterm labor; screening; progesterone;
progestins
ID SPONTANEOUS PRETERM DELIVERY; SONOGRAPHIC SHORT CERVIX; TRANSVAGINAL
ULTRASONOGRAPHIC MEASUREMENT; PREVIOUS OBSTETRIC HISTORY;
PLACEBO-CONTROLLED TRIAL; BORN EXTREMELY PRETERM; AMNIOTIC-FLUID SLUDGE;
CLINICAL-SIGNIFICANCE; VAGINAL PROGESTERONE; WEEKS GESTATION
AB Objective: To assess the diagnostic performance of transabdominal sonographic measurement of cervical length in identifying patients with a short cervix. Methods: Cervical length was measured in 220 pregnant women using transabdominal and transvaginal ultrasound (US). Reproducibility and agreement between and within both methods were assessed. The diagnostic accuracy of transabdominal US for identifying cases with a cervical length <25 mm was evaluated. Results: Twenty-one out of 220 cases (9.5%) had a cervical length <25 mm by transvaginal US. Only 43% (n = 9) of patients with a short cervix were correctly identified by transabdominal US. In patients with a cervical length of <25 mm by transvaginal US, transabdominal measurement of the cervix overestimated this parameter by an average of 8 mm (95% LOAs, -26.4 to 10.5 mm). Among women without a short cervix, transabdominal US underestimated cervical length on average (LOA) by 1.1 mm (95% LOAs, -11.0 to 13.2 mm). Transvaginal US was also more reproducible (intra-class correlation coefficient: (ICC) (0.96; 95% CI, 0.94 to 0.97) based on comparisons between 2D images and immediately acquired 3D volume datasets relative to transabdominal US (ICC: 0.71; 95% CI, 0.57 to 0.84). Transvaginal US detected 13 cases with funneling and six cases with sludge whereas only three cases of funneling and one of sludge were detected by transabdominal US. Conclusion: Transabdominal measurement overestimated cervical LOA by 8 mm among women with a short cervix and resulted in the underdiagnosis of 57% of cases.
C1 [Hernandez-Andrade, Edgar; Romero, Roberto; Ahn, Hyunyoung; Hussein, Youssef; Yeo, Lami; Korzeniewski, Steven J.; Chaiworapongsa, Tinnakorn; Hassan, Sonia S.] NICHD, Perinatol Res Branch, NIH, DHHS, Detroit, MI USA.
[Hernandez-Andrade, Edgar; Yeo, Lami; Korzeniewski, Steven J.; Chaiworapongsa, Tinnakorn; Hassan, Sonia S.] Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI USA.
RP Romero, R (reprint author), Wayne State Univ, Perinatol Res Branch, NICHD, NIH,DHHS,Hutzel Womens Hosp, 3990 John R,Box 4, Detroit, MI 48201 USA.
EM ehernand@med.wayne.edu; prbchiefstaff@med.wayne.edu
FU Perinatology Research Branch, Division of Intramural Research, Eunice
Kennedy Shriver National Institute of Child Health and Human
Development, NIH, DHHS
FX This research was supported, in part, by Perinatology Research Branch,
Division of Intramural Research, Eunice Kennedy Shriver National
Institute of Child Health and Human Development, NIH, DHHS.
NR 122
TC 29
Z9 32
U1 0
U2 2
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 1476-7058
J9 J MATERN-FETAL NEO M
JI J. Matern.-Fetal Neonatal Med.
PD SEP
PY 2012
VL 25
IS 9
BP 1682
EP 1689
DI 10.3109/14767058.2012.657278
PG 8
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 995HU
UT WOS:000307999600031
PM 22273078
ER
PT J
AU Lee, SM
Romero, R
Park, JW
Kim, SM
Park, CW
Korzeniewski, SJ
Chaiworapongsa, T
Yoon, BH
AF Lee, Seung Mi
Romero, Roberto
Park, Jeong Woo
Kim, Sun Min
Park, Chan-Wook
Korzeniewski, Steven J.
Chaiworapongsa, Tinnakorn
Yoon, Bo Hyun
TI The clinical significance of a positive Amnisure test in women with
preterm labor and intact membranes
SO JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE
LA English
DT Article
DE Adverse pregnancy outcome; infection; intact membranes; intra-amniotic
inflammation; prematurity; preterm birth
ID FLUID MATRIX METALLOPROTEINASE-8; FETAL INFLAMMATORY RESPONSE;
RANDOMIZED CONTROLLED-TRIAL; FACTOR BINDING PROTEIN-1; C-REACTIVE
PROTEIN; MMP-8 BEDSIDE TEST; PREMATURE RUPTURE; AMNIOTIC-FLUID;
INTRAAMNIOTIC INFECTION; ANTENATAL CORTICOSTEROIDS
AB Objective: This study was conducted to examine the frequency and clinical significance of a positive Amnisure test in patients with preterm labor and intact membranes by sterile speculum exam. Study design: A retrospective cohort study was performed including 90 patients with preterm labor and intact membranes who underwent Amnisure tests prior to amniocentesis (72 h); most patients (n = 64) also underwent fetal fibronectin (fFN) tests. Amniotic fluid (AF) was cultured for aerobic/anaerobic bacteria and genital mycoplasmas and assayed for matrix metalloproteinase-8. Results: (1) the prevalence of a positive Amnisure test was 19% (17/90); (2) patients with a positive Amnisure test had significantly higher rates of adverse pregnancy and neonatal outcomes (e.g., impending preterm delivery, intra-amniotic infection/inflammation, and neonatal morbidity) than those with a negative Amnisure test; (3) a positive test was associated with significantly increased risk of intra-amniotic infection and/or inflammation, delivery within 7, 14, or 28 days and spontaneous preterm birth (< 35 weeks) among patients with a negative fFN test. Conclusions: A positive Amnisure test in patients with preterm labor and intact membranes is a risk factor for adverse pregnancy outcome, particularly in patients with a negative fFN test. A positive Amnisure test in patients without symptoms or signs of ROM should not be taken as an indicator that membranes have ruptured.
C1 [Lee, Seung Mi; Park, Jeong Woo; Kim, Sun Min; Park, Chan-Wook; Yoon, Bo Hyun] Seoul Natl Univ, Coll Med, Dept Obstet & Gynecol, Seoul 110744, South Korea.
[Lee, Seung Mi] Seoul Natl Univ, Seoul Metropolitan Govt, Boramae Med Ctr, Dept Obstet & Gynecol, Seoul 110744, South Korea.
[Romero, Roberto; Korzeniewski, Steven J.; Chaiworapongsa, Tinnakorn] NICHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD USA.
[Romero, Roberto; Korzeniewski, Steven J.; Chaiworapongsa, Tinnakorn] NICHD, Perinatol Res Branch, NIH, DHHS, Detroit, MI USA.
[Korzeniewski, Steven J.; Chaiworapongsa, Tinnakorn] Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA.
RP Yoon, BH (reprint author), Seoul Natl Univ, Coll Med, Dept Obstet & Gynecol, Seoul 110744, South Korea.
EM yoonbh@snu.ac.kr
RI Yoon, Bo Hyun/H-6344-2011; Park, Chan-Wook/J-5498-2012;
OI Park, Jeong Woo/0000-0001-6499-0814
FU National Research Foundation of Korea (NRF); Korea government (MEST)
[2011-0000195]; Eunice Kennedy Shriver National Institute of Child
Health and Human Development, NIH/DHHS
FX This work was supported by the National Research Foundation of Korea
(NRF) grant funded by the Korea government (MEST) (No. 2011-0000195),
and, in part, by the Eunice Kennedy Shriver National Institute of Child
Health and Human Development, NIH/DHHS.
NR 147
TC 13
Z9 16
U1 0
U2 8
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 1476-7058
J9 J MATERN-FETAL NEO M
JI J. Matern.-Fetal Neonatal Med.
PD SEP
PY 2012
VL 25
IS 9
BP 1690
EP 1698
DI 10.3109/14767058.2012.657279
PG 9
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 995HU
UT WOS:000307999600032
PM 22280400
ER
PT J
AU Shen, JX
Yakel, JL
AF Shen, Jian-xin
Yakel, Jerrel L.
TI Functional alpha 7 Nicotinic ACh Receptors on Astrocytes in Rat
Hippocampal CA1 Slices
SO JOURNAL OF MOLECULAR NEUROSCIENCE
LA English
DT Article
DE Nicotinic receptor; Calcium signaling; Patch-clamp
ID LONG-TERM POTENTIATION; ACETYLCHOLINE-RECEPTOR; ALZHEIMERS-DISEASE;
SYNAPTIC PLASTICITY; CHOLINERGIC MODULATION; COGNITIVE FUNCTION; AMYLOID
PLAQUES; GLIAL-CELLS; MOUSE MODEL; CALCIUM
AB Although much is known about the functional expression of the neuronal nicotinic acetylcholine receptors (nAChRs) in various neuronal populations in the brain and elsewhere, much less is known about their expression and functional relevance in glial cells. The expression of functional nAChRs has been reported for cultured astrocytes; however, previous work has failed to detect nAChR-mediated responses in astrocytes in acute slices. In the current study, functional alpha 7 nAChRs on astrocytes in the CA1 region of the rat hippocampus were studied in situ using whole-cell patch-clamp recording and two-photon calcium imaging techniques in acute slices. We found that astrocytes and the chondroitin sulfate proteoglycan NG2-expressing (i.e., NG2) cells did express functional alpha 7 nAChRs. Although the amplitudes of the responses were small, they could be enhanced by the alpha 7-selective positive allosteric modulator PNU-120596. Under these conditions, we found that in comparing the properties of these responses between astrocytes, NG2, and interneurons, there were differences in the kinetics and increases in intracellular calcium levels. This is the first demonstration of functional alpha 7 nAChR-mediated current responses in astrocytes in acute hippocampal slices, data which may shed light on the role of alpha 7 nAChRs in neuroprotection.
C1 [Yakel, Jerrel L.] NIEHS, Neurobiol Lab, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA.
RP Yakel, JL (reprint author), NIEHS, Neurobiol Lab, NIH, Dept Hlth & Human Serv, POB 12233,111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA.
EM jxshen@stu.edu.cn; yakel@niehs.nih.gov
FU NIH, National Institute of Environmental Health Sciences; National
Natural Science Foundation of China [31171089]
FX We would like to thank C. Erxleben for the advice in preparing the
manuscript. Research was supported by the Intramural Research Program of
the NIH, National Institute of Environmental Health Sciences. Further
support was provided to Jian-xin Shen by the National Natural Science
Foundation of China (No. 31171089).
NR 50
TC 37
Z9 38
U1 1
U2 11
PU HUMANA PRESS INC
PI TOTOWA
PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA
SN 0895-8696
J9 J MOL NEUROSCI
JI J. Mol. Neurosci.
PD SEP
PY 2012
VL 48
IS 1
BP 14
EP 21
DI 10.1007/s12031-012-9719-3
PG 8
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA 986HZ
UT WOS:000307334000002
PM 22351110
ER
PT J
AU Purohit, V
Rapaka, RS
Rutter, J
Shurtleff, D
AF Purohit, Vishnudutt
Rapaka, Rao S.
Rutter, Joni
Shurtleff, David
TI Do Opioids Activate Latent HIV-1 by Down-Regulating Anti-HIV microRNAs?
SO JOURNAL OF NEUROIMMUNE PHARMACOLOGY
LA English
DT Review
DE Anti-HIV-1 microRNAs; Morphine; CD4+T cells; Monocytes/macrophages; HIV
latency
ID BLOOD MONONUCLEAR PHAGOCYTES; INTERFERON-ALPHA EXPRESSION;
ANTIRETROVIRAL THERAPY; MEDIATED-ENHANCEMENT; CELLULAR MICRORNAS;
MORPHINE TREATMENT; VIRUS-REPLICATION; GENE-EXPRESSION; MESSENGER-RNA;
INFECTION
AB Researchers have recently demonstrated the presence of anti-HIV-1 microRNAs (miR-28, miR-125b, miR-150, miR-223, and miR-382) in monocytes, macrophages, and CD4+ T cells, which are the primary targets of HIV infection. These miRNAs appear to regulate the level of infectivity of HIV-1 in the target cells, and thus have an impact on HIV-1 latency. The levels of these miRNAs are significantly higher in resting CD4+ T cells than those in active CD4+ T cells, whereas HIV-1 infectivity is greater in active than in resting CD4+ T cells. Similarly, the levels of these miRNAs are significantly higher in monocytes than in macrophages, whereas HIV-1 infectivity is greater in macrophages than in monocytes. Down-regulation or inhibition of the activity of these miRNAs can promote replication of latent HIV-1 in resting CD4+ T cells and in monocytes. Recently, morphine was shown to down regulate the expression of anti-HIV miRNAs (miRNA-28, 125b, 150, and 382) in cultured human monocytes and this effect of morphine was mediated via activation of mu opioid receptors (MOR). In addition, levels of these anti-HIV miRNAs were significantly lower in the peripheral blood mononuclear cells (PBMCs) isolated from heroin-dependent subjects than those from control subjects. These findings raise an important question: Does morphine have potential to activate latent HIV-1 in resting CD4+ T cells and macrophages, including microglia of human subjects maintained on highly active antiretroviral therapy (HAART)? Further research is required to answer this question.
C1 [Purohit, Vishnudutt; Rapaka, Rao S.; Rutter, Joni; Shurtleff, David] NIDA, Chem & Physiol Syst Res Branch, Div Basic Neurosci & Behav Res, NIH, Bethesda, MD 20892 USA.
RP Purohit, V (reprint author), NIDA, Chem & Physiol Syst Res Branch, Div Basic Neurosci & Behav Res, NIH, 6001 Execut Blvd Room 4275,MSC 9555, Bethesda, MD 20892 USA.
EM vpurohit@nida.nih.gov
OI Rutter, Joni/0000-0002-6502-2361
NR 34
TC 8
Z9 9
U1 1
U2 8
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1557-1890
J9 J NEUROIMMUNE PHARM
JI J. Neuroimmune Pharm.
PD SEP
PY 2012
VL 7
IS 3
BP 519
EP 523
DI 10.1007/s11481-012-9356-1
PG 5
WC Neurosciences; Pharmacology & Pharmacy
SC Neurosciences & Neurology; Pharmacology & Pharmacy
GA 989JL
UT WOS:000307556000002
PM 22527633
ER
PT J
AU Ramadan, E
Basselin, M
Chang, L
Chen, M
Ma, KZ
Rapoport, SI
AF Ramadan, Epolia
Basselin, Mireille
Chang, Lisa
Chen, Mei
Ma, Kaizong
Rapoport, Stanley I.
TI Chronic Lithium Feeding Reduces Upregulated Brain Arachidonic Acid
Metabolism in HIV-1 Transgenic Rat
SO JOURNAL OF NEUROIMMUNE PHARMACOLOGY
LA English
DT Article
DE HIV-1; Lithium; Arachidonic acid; Brain imaging; Phospholipase A(2);
Metabolism
ID CENTRAL-NERVOUS-SYSTEM; GLYCOGEN-SYNTHASE KINASE-3; CYCLIN-DEPENDENT
KINASE-5; DOCOSAHEXAENOIC ACID; UNANESTHETIZED RATS; MOOD STABILIZERS;
NEUROCOGNITIVE IMPAIRMENT; ALZHEIMERS-DISEASE; PROTEIN EXPRESSION;
LIPID-METABOLISM
AB HIV-1 transgenic (Tg) rats, a model for human HIV-1 associated neurocognitive disorder (HAND), show upregulated markers of brain arachidonic acid (AA) metabolism with neuroinflammation after 7 months of age. Since lithium decreases AA metabolism in a rat lipopolysaccharide model of neuroinflammation, and may be useful in HAND, we hypothesized that lithium would dampen upregulated brain AA metabolism in HIV-1 Tg rats. Regional brain AA incorporation coefficients k* and rates J (in) , markers of AA signaling and metabolism, were measured in 81 brain regions using quantitative autoradiography, after intravenous [1-(14) C]AA infusion in unanesthetized 10-month-old HIV-1 Tg and age-matched wildtype rats that had been fed a control or LiCl diet for 6 weeks. k* and J (in) for AA were significantly higher in HIV-1 Tg than wildtype rats fed the control diet. Lithium feeding reduced plasma unesterified AA concentration in both groups and J (in) in wildtype rats, and blocked increments in k* (19 of 54 regions) and J (in) (77 of 81 regions) in HIV-1 Tg rats. These in vivo neuroimaging data indicate that lithium treatment dampened upregulated brain AA metabolism in HIV-1 Tg rats. Lithium may improve cognitive dysfunction and be neuroprotective in HIV-1 patients with HAND through a comparable effect.
C1 [Ramadan, Epolia; Basselin, Mireille; Chang, Lisa; Chen, Mei; Ma, Kaizong; Rapoport, Stanley I.] NIA, Brain Physiol & Metab Sect, NIH, Bethesda, MD 20892 USA.
RP Basselin, M (reprint author), NIA, Brain Physiol & Metab Sect, NIH, 9000 Rockville Pike,Bldg 9,Rm 1S126 MSC 0947, Bethesda, MD 20892 USA.
EM mirvasln@mail.nih.gov
FU National Institute on Aging, NIH
FX The research was supported entirely by the Intramural Research Program
of the National Institute on Aging, NIH. No author has a financial or
other conflict of interest related to this work.
NR 91
TC 2
Z9 2
U1 0
U2 2
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1557-1890
J9 J NEUROIMMUNE PHARM
JI J. Neuroimmune Pharm.
PD SEP
PY 2012
VL 7
IS 3
BP 701
EP 713
DI 10.1007/s11481-012-9381-0
PG 13
WC Neurosciences; Pharmacology & Pharmacy
SC Neurosciences & Neurology; Pharmacology & Pharmacy
GA 989JL
UT WOS:000307556000021
PM 22760927
ER
PT J
AU Zadeh, S
Gamba, N
Hudson, C
Wiener, L
AF Zadeh, Sima
Gamba, Nicole
Hudson, Caroline
Wiener, Lori
TI Taking Care of Care Providers: A Wellness Program for Pediatric Nurses
SO JOURNAL OF PEDIATRIC ONCOLOGY NURSING
LA English
DT Article
DE staff wellness; oncology nursing; compassion fatigue; education; burnout
ID COMPASSION FATIGUE; BURNOUT; STAFF
AB The cumulative effect of professional stress and compassion fatigue within the health care profession has been receiving increasing attention. The impact can be especially worrisome for nurses who work with chronic illness populations, such as oncology. While interventions targeted at reducing nurses stress and promoting wellness are cited as necessary, they are often lacking in busy medical environments. In this article, the authors describe a newly developed 10-session wellness program that was offered on 2 occasions to both inpatient and outpatient nursing staff. The nursing staff chose the content areas, and each session used a combined approach of hands on and didactic learning. A description of the activity offered during each session along with the core competency and objectives measured are provided. Overall, staff found the wellness series very helpful to themselves and to their ability to positively change their job performance.
C1 [Zadeh, Sima] NCI, NIH, Pediat Clin, Pediat Oncol Branch, Bethesda, MD 20892 USA.
[Gamba, Nicole] NIH, Ctr Clin, Pediat Inpatient Unit, Bethesda, MD 20892 USA.
[Gamba, Nicole] NIH, Ctr Clin, Day Hosp, Bethesda, MD 20892 USA.
[Hudson, Caroline] NIH, Ctr Clin, Pediat Unit, Bethesda, MD 20892 USA.
RP Zadeh, S (reprint author), NCI, NIH, Pediat Clin, Pediat Oncol Branch, 10 Ctr Dr,1-5460, Bethesda, MD 20892 USA.
EM zadehsl@mail.nih.gov
FU Intramural NIH HHS [Z99 CA999999]
NR 16
TC 7
Z9 9
U1 6
U2 26
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1043-4542
J9 J PEDIATR ONCOL NURS
JI J. Pediatr. Oncol. Nurs.
PD SEP-OCT
PY 2012
VL 29
IS 5
BP 294
EP 299
DI 10.1177/1043454212451793
PG 6
WC Oncology; Nursing
SC Oncology; Nursing
GA 990OD
UT WOS:000307639400007
PM 22907685
ER
PT J
AU Rotinen, M
Villar, J
Encio, I
AF Rotinen, Mirja
Villar, Joaquin
Encio, Ignacio
TI Regulation of 17 beta-hydroxysteroid dehydrogenases in cancer:
regulating steroid receptor at pre-receptor stage
SO JOURNAL OF PHYSIOLOGY AND BIOCHEMISTRY
LA English
DT Review
DE Endocrine-related cancer; Androgens; Estrogens; Steroid receptor;
HSD17Bs; Inhibitor
ID NUCLEAR HORMONE-RECEPTORS; SURFACE EPITHELIAL-CELLS; HUMAN
PROSTATE-CANCER; BREAST-CANCER; ENDOMETRIAL CANCER; ESTROGEN-RECEPTOR;
IN-SITU; ANDROGEN RECEPTOR; 3-ALPHA-HYDROXYSTEROID DEHYDROGENASE;
METABOLIZING ENZYMES
AB Increased intracelullar hormone concentration levels have been shown to be the cause of several endocrine-related cancers including breast, prostate, endometrial, ovarian, cervix, testicular, thyroid, and osteosarcoma. Deregulated expression of steroidogenic enzymes in these tumors seems to be the source of a positive balance in active steroids that bind to the corresponding nuclear receptor, thus ultimately stimulating cell proliferation. Among these enzymes, 17 beta-hydroxysteroid dehydrogenases catalyze the interconversion between 17-ketosteroids and 17-hydroxysteroids on the last steps of sex hormones biosynthesis and metabolism. To date, 14 isoforms have been identified in vertebrates although only 13 are present in humans. Development and clinical evaluation of specific inhibitors to block their activity is currently under progress especially against the best characterized members 1 to 5. Selectivity and potency of these drugs constitute the main challenge in this new approach to cancer and steroid-dependent diseases treatment at the "pre-receptor level". Here we review the current state of knowledge regarding the deregulation of the expression of some of these enzymes in endocrine-related tumors.
C1 [Rotinen, Mirja; Villar, Joaquin; Encio, Ignacio] Univ Publ Navarra, Dept Hlth Sci, Pamplona 31008, Spain.
[Villar, Joaquin] NICHD, Sect Mol Endocrinol, PDEGEN, NIH, Bethesda, MD 20892 USA.
RP Encio, I (reprint author), Univ Publ Navarra, Dept Hlth Sci, Avda Baranain, Pamplona 31008, Spain.
EM ignacio.encio@unavarra.es
NR 129
TC 4
Z9 4
U1 1
U2 18
PU SERVICIO PUBLICACIONES UNIVERSIDAD NAVARRA
PI PAMPLONA
PA CAMPUS UNIV, CARRETERA DEL SADAR S-N, APARTADO 177, 31080 PAMPLONA,
SPAIN
SN 1138-7548
EI 1877-8755
J9 J PHYSIOL BIOCHEM
JI J. Physiol. Biochem.
PD SEP
PY 2012
VL 68
IS 3
BP 461
EP 473
DI 10.1007/s13105-012-0155-1
PG 13
WC Biochemistry & Molecular Biology; Physiology
SC Biochemistry & Molecular Biology; Physiology
GA 988TL
UT WOS:000307513500016
PM 22374586
ER
PT J
AU Orlov, NV
Eckley, DM
Shamir, L
Goldberg, IG
AF Orlov, Nikita V.
Eckley, D. Mark
Shamir, Lior
Goldberg, Ilya G.
TI Improving class separability using extended pixel planes: a comparative
study
SO MACHINE VISION AND APPLICATIONS
LA English
DT Article
DE Multi-scale representations; Transforms; Spectral features
ID IMAGE-ANALYSIS; SUBCELLULAR STRUCTURES; PATTERN-RECOGNITION; MICROSCOPIC
IMAGES; GLOBAL FEATURES; CLASSIFICATION; SCALE
AB In this work we explored class separability in feature spaces built on extended representations of pixel planes (EPP) produced using scale pyramid, subband pyramid, and image transforms. The image transforms included Chebyshev, Fourier, wavelets, gradient, and Laplacian; we also utilized transform combinations, including Fourier, Chebyshev, and wavelets of the gradient transform, as well as Fourier of the Laplacian transform. We demonstrate that all three types of EPP promote class separation. We also explored the effect of EPP on suboptimal feature libraries, using only textural features in one case and only Haralick features in another. The effect of EPP was especially clear for these suboptimal libraries, where the transform-based representations were found to increase separability to a greater extent than scale or subband pyramids. EPP can be particularly useful in new applications where optimal features have not yet been developed.
C1 [Orlov, Nikita V.; Eckley, D. Mark; Shamir, Lior; Goldberg, Ilya G.] NIA, NIH, Baltimore, MD 21224 USA.
[Shamir, Lior] Lawrence Technol Univ, Dept Math & Comp Sci, Southfield, MI 48075 USA.
RP Orlov, NV (reprint author), NIA, NIH, 251 Bayview Blvd,Bayview Res Ctr Bld,Suite 100, Baltimore, MD 21224 USA.
EM norlov@nih.gov; dme@nih.gov; Ishamir@ltu.edu; igg@nih.gov
RI Eckley, Mark/M-3526-2014
OI Eckley, Mark/0000-0003-2296-5164
FU NIH, National Institute on Aging
FX This research was supported by the Intramural Research Program of the
NIH, National Institute on Aging.
NR 42
TC 1
Z9 1
U1 0
U2 1
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0932-8092
J9 MACH VISION APPL
JI Mach. Vis. Appl.
PD SEP
PY 2012
VL 23
IS 5
BP 1047
EP 1058
DI 10.1007/s00138-011-0349-5
PG 12
WC Computer Science, Artificial Intelligence; Computer Science,
Cybernetics; Engineering, Electrical & Electronic
SC Computer Science; Engineering
GA 989DB
UT WOS:000307539300015
PM 23074356
ER
PT J
AU Sandler, NG
Douek, DC
AF Sandler, Netanya G.
Douek, Daniel C.
TI Microbial translocation in HIV infection: causes, consequences and
treatment opportunities
SO NATURE REVIEWS MICROBIOLOGY
LA English
DT Review
ID HUMAN-IMMUNODEFICIENCY-VIRUS; ACTIVE ANTIRETROVIRAL THERAPY;
INFLAMMATORY-BOWEL-DISEASE; T-CELL-ACTIVATION; INTESTINAL
EPITHELIAL-CELLS; TOLL-LIKE RECEPTORS; NONCIRRHOTIC PORTAL-HYPERTENSION;
MUCOSAL IMMUNE RECONSTITUTION; TISSUE FACTOR EXPRESSION;
TUMOR-NECROSIS-FACTOR
AB Systemic immune activation is increased in HIV-infected individuals, even in the setting of virus suppression with antiretroviral therapy. Although numerous factors may contribute, microbial products have recently emerged as potential drivers of this immune activation. In this Review, we describe the intestinal damage that occurs in HIV infection, the evidence for translocation of microbial products into the systemic circulation and the pathways by which these products activate the immune system. We also discuss novel therapies that disrupt the translocation of microbial products and the downstream effects of microbial translocation.
C1 [Sandler, Netanya G.; Douek, Daniel C.] NIAID, Human Immunol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
RP Douek, DC (reprint author), NIAID, Human Immunol Sect, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM ddouek@mail.nih.gov
OI Utay, Netanya/0000-0002-6407-8670
FU NIAID NIH HHS [AI-76174]
NR 167
TC 151
Z9 151
U1 0
U2 26
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1740-1526
J9 NAT REV MICROBIOL
JI Nat. Rev. Microbiol.
PD SEP
PY 2012
VL 10
IS 9
BP 655
EP 666
DI 10.1038/nrmicro2848
PG 12
WC Microbiology
SC Microbiology
GA 993PE
UT WOS:000307871000016
PM 22886237
ER
PT J
AU Banerjee, A
Tognoli, E
Kelso, JAS
Jirsa, VK
AF Banerjee, Arpan
Tognoli, Emmanuelle
Kelso, J. A. Scott
Jirsa, Viktor K.
TI Spatiotemporal re-organization of large-scale neural assemblies
underlies bimanual coordination
SO NEUROIMAGE
LA English
DT Article
DE Unimanual; Bimanual; Coordination; Recruitment; Temporal modulation;
EEG; MEG; Mode level cognitive subtraction; Event related potentials
ID SUPPLEMENTARY MOTOR AREA; TRANSCRANIAL MAGNETIC STIMULATION; IN-PHASE
MOVEMENTS; HUMAN BRAIN; FINGER MOVEMENTS; INTERHEMISPHERIC INHIBITION;
SENSORIMOTOR CORTEX; HAND MOVEMENTS; FUNCTIONAL MRI; ACTIVATION
AB Bimanual coordination engages a distributed network of brain areas, the spatiotemporal organization of which has given rise to intense debates. Do bimanual movements require information processing in the same set of brain areas that are engaged by movements of the individual components (left and right hands)? Or is it necessary that other brain areas are recruited to help in the act of coordination? These two possibilities are often considered as mutually exclusive, with studies yielding support for one or the other depending on techniques and hypotheses. However, as yet there is no account of how the two views may work together dynamically. Using the method of Mode-Level Cognitive Subtraction (MLCS) on high density EEG recorded during unimanual and bimanual movements, we expose spatiotemporal reorganization of large-scale cortical networks during stable inphase and antiphase coordination and transitions between them. During execution of stable bimanual coordination patterns, neural dynamics were dominated by temporal modulation of unimanual networks. At instability and transition, there was evidence for recruitment of additional areas. Our study provides a framework to quantify large-scale network mechanisms underlying complex cognitive tasks often studied with macroscopic neurophysiological recordings. (c) 2012 Elsevier Inc. All rights
C1 [Banerjee, Arpan; Tognoli, Emmanuelle; Kelso, J. A. Scott] Florida Atlantic Univ, Ctr Complex Syst & Brain Sci, Boca Raton, FL 33431 USA.
[Kelso, J. A. Scott] Univ Ulster, Intelligent Syst Res Ctr, Coleraine BT52 1SA, Londonderry, North Ireland.
[Jirsa, Viktor K.] Aix Marseille Univ, UMR Inserm 1106, Fac Med, Inst Neurosci Syst, F-13005 Marseille, France.
RP Banerjee, A (reprint author), Natl Inst Deafness & Other Commun Disorders, NIH, 10 Ctr Dr,5D39,Bldg 10, Bethesda, MD 20892 USA.
EM banerjeea2@mail.nih.gov
RI Jirsa, Viktor/M-4630-2016;
OI Jirsa, Viktor/0000-0002-8251-8860; Tognoli,
Emmanuelle/0000-0003-3674-504X
FU Brain Network Recovery Group through the James S. McDonnell Foundation;
FP7-ICT Brain Scales; NIMH [MH080838]; NSF [BCS0826897]; US Office of
Naval Research [N000140510117]; Chaire d'Excellence Pierre de Fermat;
Davimos Family Endowment for Excellence in Science
FX This work was supported by the grants Brain Network Recovery Group
through the James S. McDonnell Foundation and the FP7-ICT Brain Scales
to VKJ. ET and JASK were supported by NIMH grant MH080838, NSF grant
BCS0826897, US Office of Naval Research Contract N000140510117, the
Chaire d'Excellence Pierre de Fermat (JASK) and the Davimos Family
Endowment for Excellence in Science (ET). We thank Allison De Larosiere
for her contribution to data collection. AB acknowledges Dr. Bijan
Pesaran for helpful discussions and Dr. Ajay Pillai for useful comments.
NR 76
TC 12
Z9 12
U1 5
U2 29
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 2012
VL 62
IS 3
BP 1582
EP 1592
DI 10.1016/j.neuroimage.2012.05.046
PG 11
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 986TR
UT WOS:000307369000026
PM 22634864
ER
PT J
AU Banerjee, A
Pillai, AS
Sperling, JR
Smith, JF
Horwitz, B
AF Banerjee, Arpan
Pillai, Ajay S.
Sperling, Justin R.
Smith, Jason F.
Horwitz, Barry
TI Temporal microstructure of cortical networks (TMCN) underlying
task-related differences
SO NEUROIMAGE
LA English
DT Article
DE EEG; MEG; Network timing; Decoding; Event related potential; Event
related field; Multivariate; SAM; Source analysis; Forward solution
ID POSITRON-EMISSION-TOMOGRAPHY; REALISTIC VOLUME CONDUCTORS; PARTIAL
LEAST-SQUARES; SHORT-TERM-MEMORY; PREFRONTAL CORTEX; WORKING-MEMORY;
HUMAN BRAIN; SPATIOTEMPORAL ANALYSIS; STRUCTURAL DESCRIPTIONS; FIELD
POTENTIALS
AB Neuro-electromagnetic recording techniques (EEG. MEG, iEEG) provide high temporal resolution data to study the dynamics of neurocognitive networks: large scale neural assemblies involved in task-specific information processing. How does a neurocognitive network reorganize spatiotemporally on the order of a few milliseconds to process specific aspects of the task? At what times do networks segregate for task processing, and at what time scales does integration of information occur via changes in functional connectivity? Here, we propose a data analysis framework-Temporal microstructure of cortical networks (TMCN)-that answers these questions for EEG/MEG recordings in the signal space. Method validation is established on simulated MEG data from a delayed-match to-sample (DMS) task. We then provide an example application on MEG recordings during a paired associate task (modified from the simpler DMS paradigm) designed to study modality specific long term memory recall. Our analysis identified the times at which network segregation occurs for processing the memory recall of an auditory object paired to a visual stimulus (visual-auditory) in comparison to an analogous visual-visual pair. Across all subjects, onset times for first network divergence appeared within a range of 0.08-0.47 s after initial visual stimulus onset. This indicates that visual-visual and visual auditory memory recollection involves equivalent network components without any additional recruitment during an initial period of the sensory processing stage which is then followed by recruitment of additional network components for modality specific memory recollection. Therefore, we propose TMCN as a viable computational tool for extracting network timing in various cognitive tasks. Published by Elsevier Inc.
C1 [Banerjee, Arpan; Pillai, Ajay S.; Sperling, Justin R.; Smith, Jason F.; Horwitz, Barry] Natl Inst Deafness & Other Commun Disorders, Brain Imaging & Modeling Sect, NIH, Bethesda, MD 20892 USA.
RP Banerjee, A (reprint author), Natl Inst Deafness & Other Commun Disorders, Brain Imaging & Modeling Sect, NIH, 10 Ctr Dr,Room 5D39, Bethesda, MD 20892 USA.
EM Arpan.Banerjee@nih.gov
FU NIDCD intramural research program
FX This research was supported by the NIDCD intramural research program.
NR 80
TC 4
Z9 4
U1 2
U2 3
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 2012
VL 62
IS 3
BP 1643
EP 1657
DI 10.1016/j.neuroimage.2012.06.014
PG 15
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 986TR
UT WOS:000307369000032
PM 22728151
ER
PT J
AU Yang, X
Lauzon, CB
Crainiceanu, C
Caffo, B
Resnick, SM
Landman, BA
AF Yang, Xue
Lauzon, Carolyn B.
Crainiceanu, Ciprian
Caffo, Brian
Resnick, Susan M.
Landman, Bennett A.
TI Biological parametric mapping accounting for random regressors with
regression calibration and model II regression
SO NEUROIMAGE
LA English
DT Article
DE Structure-function relationships; Random regressors; Regression
calibration; Model II regression; General linear model
ID BAYESIAN-INFERENCE
AB Massively univariate regression and inference in the form of statistical parametric mapping have transformed the way in which multi-dimensional imaging data are studied. In functional and structural neuroimaging, the de facto standard "design matrix"-based general linear regression model and its multi-level cousins have enabled investigation of the biological basis of the human brain. With modem study designs, it is possible to acquire multi-modal three-dimensional assessments of the same individuals-e.g., structural, functional and quantitative magnetic resonance imaging, alongside functional and ligand binding maps with positron emission tomography. Largely, current statistical methods in the imaging community assume that the regressors are non-random. For more realistic multi-parametric assessment (e.g., voxel-wise modeling), distributional consideration of all observations is appropriate. Herein, we discuss two unified regression and inference approaches, model II regression and regression calibration, for use in massively univariate inference with imaging data. These methods use the design matrix paradigm and account for both random and non-random imaging regressors. We characterize these methods in simulation and illustrate their use on an empirical dataset. Both methods have been made readily available as a toolbox plug-in for the SPM software. (c) 2012 Elsevier Inc. All rights reserved.
C1 [Yang, Xue; Lauzon, Carolyn B.; Landman, Bennett A.] Vanderbilt Univ, Nashville, TN 37235 USA.
[Resnick, Susan M.] NIA, NIH, Baltimore, MD 21224 USA.
[Crainiceanu, Ciprian; Caffo, Brian] Johns Hopkins Univ, Sch Publ Hlth, Baltimore, MD 21218 USA.
[Landman, Bennett A.] Johns Hopkins Univ, Baltimore, MD 21205 USA.
RP Landman, BA (reprint author), Vanderbilt Univ EECS, 2301 Vanderbilt Pl,POB 351679 Stn B, Nashville, TN 37235 USA.
EM bennett.landman@vanderbilt.edu
FU NIH [N01-AG-4-0012, T32EB003817, R01EB012547, R01NS060910, P41 EB015909]
FX This project was supported in part by grants NIH N01-AG-4-0012, NIH
T32EB003817, NIH R01EB012547, NIH R01NS060910, and NIH P41 EB015909.
This work represents the opinions of the researchers and not necessarily
that of the granting organizations. We are especially grateful for the
valuable contributions of the anonymous reviewers.
NR 20
TC 2
Z9 2
U1 0
U2 1
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1053-8119
J9 NEUROIMAGE
JI Neuroimage
PD SEP
PY 2012
VL 62
IS 3
BP 1761
EP 1768
DI 10.1016/j.neuroimage.2012.05.020
PG 8
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 986TR
UT WOS:000307369000043
PM 22609453
ER
PT J
AU Lu, HB
Chefer, S
Kurup, PK
Guillem, K
Vaupel, DB
Ross, TJ
Moore, A
Yang, YH
Peoples, LL
Stein, EA
AF Lu, Hanbing
Chefer, Svetlana
Kurup, Pradeep K.
Guillem, Karine
Vaupel, D. Bruce
Ross, Thomas J.
Moore, Anna
Yang, Yihong
Peoples, Laura L.
Stein, Elliot A.
TI fMRI response in the medial prefrontal cortex predicts cocaine but not
sucrose self-administration history
SO NEUROIMAGE
LA English
DT Article
DE Neuroadaptation; Self-administration; Abstinence; Pharmacological MRI
ID CEREBRAL BLOOD-VOLUME; NUCLEUS-ACCUMBENS; DRUG-SEEKING; FUNCTIONAL
CONNECTIVITY; GLUTAMATE TRANSMISSION; INDUCED REINSTATEMENT; MEDIODORSAL
NUCLEUS; REWARD REGIONS; IN-VIVO; ADDICTION
AB Repeated cocaine exposure induces long-lasting neuroadaptations that alter subsequent responsiveness to the drug. However, systems-level investigation of these neuroplastic consequences is limited. We employed a rodent model of drug addiction to investigate neuroadaptations associated with prolonged forced abstinence after long-term cocaine self-administration (SA). Since natural rewards also activate the mesolimbic reward system in a partially overlapping fashion as cocaine, our design also included a sucrose SA group. Rats were trained to self-administer cocaine or sucrose using a fixed-ratio one, long-access schedule (6 h/day for 20 days). A third group of naive, sedentary rats served as a negative control. After 30 days of abstinence, the reactivity of the reward system was assessed with functional magnetic resonance imaging (fMRI) following an intravenous cocaine injection challenge. A strong positive fMRI response, as measured by fractional cerebral blood volume changes relative to baseline (CBV%), was seen in the sedentary control group in such cortico-limbic regions as medial prefrontal cortex and anterior cingulate cortex. In contrast, both the cocaine and sucrose SA groups demonstrated a very similar initial negative fMRI response followed by an attenuated positive response. The magnitude of the mPFC response was significantly correlated with the total amount of reinforcer intake during the training sessions for the cocaine SA but not for the sucrose SA group. Given that the two SA groups had identical histories of operant training and handling, this region-specific group difference revealed by regression analysis may reflect the development of neuroadaptive mechanisms specifically related to the emergence of addiction-like behavior that occurs only in cocaine SA animals. Published by Elsevier Inc.
C1 [Lu, Hanbing; Chefer, Svetlana; Kurup, Pradeep K.; Vaupel, D. Bruce; Ross, Thomas J.; Yang, Yihong; Stein, Elliot A.] NIDA, Neuroimaging Res Branch, NIH, Baltimore, MD 21224 USA.
[Guillem, Karine; Peoples, Laura L.] Univ Penn, Dept Psychiat, TRL, Philadelphia, PA 19104 USA.
[Moore, Anna] Massachusetts Gen Hosp, MGH MIT HMS Athinoula A Martinos Ctr Biomed Imagi, Dept Radiol, Mol Imaging Lab, Boston, MA 02129 USA.
[Peoples, Laura L.] Univ Penn, Neurosci Grad Grp, Philadelphia, PA 19104 USA.
[Guillem, Karine] Univ Bordeaux, Inst Malad Neurodegenerat, UMR 5293, F-33000 Bordeaux, France.
[Peoples, Laura L.] Drexel Univ, Dept Physiol & Pharmacol, Coll Med, Philadelphia, PA 19102 USA.
[Guillem, Karine] CNRS, Inst Malad Neurodegenerat, UMR 5293, F-33000 Bordeaux, France.
RP Stein, EA (reprint author), NIDA, Neuroimaging Res Branch, NIH, 251 Bayview Blvd,Suite 200,RM7A711, Baltimore, MD 21224 USA.
EM estein@mail.nih.gov
RI Ross, Thomas/B-7469-2008
OI Ross, Thomas/0000-0002-7745-3572
FU Intramural Research Program of the National Institute on Drug Abuse
(NIDA); NIH Director's Bench-to-Bedside grant; Institute for
Translational Medicine and Therapeutics of the University of
Pennsylvania; National Center for Research Resources [UL1RR024134];
[P50DA012756]; [R01 552981]
FX We thank William Rea for his excellent technical assistance. This work
was supported by the Intramural Research Program of the National
Institute on Drug Abuse (NIDA) and by an NIH Director's Bench-to-Bedside
grant to L. L. Peoples and E. A Stein. It was also partially supported
by P50DA012756, and R01 552981 (L.L.P.), Institute for Translational
Medicine and Therapeutics of the University of Pennsylvania, and grant
UL1RR024134 from the National Center for Research Resources. The content
is solely the responsibility of the authors and does not necessarily
represent the official views of the National Center for Research
Resources or the National Institutes of Health.
NR 70
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Z9 10
U1 2
U2 7
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1053-8119
J9 NEUROIMAGE
JI Neuroimage
PD SEP
PY 2012
VL 62
IS 3
BP 1857
EP 1866
DI 10.1016/j.neuroimage.2012.05.076
PG 10
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 986TR
UT WOS:000307369000054
PM 22664568
ER
PT J
AU Podell, JE
Sambataro, F
Murty, VP
Emery, MR
Tong, YX
Das, S
Goldberg, TE
Weinberger, DR
Mattay, VS
AF Podell, Jamie E.
Sambataro, Fabio
Murty, Vishnu P.
Emery, Matthew R.
Tong, Yunxia
Das, Saumitra
Goldberg, Terry E.
Weinberger, Daniel R.
Mattay, Venkata S.
TI Neurophysiological correlates of age-related changes in working memory
updating
SO NEUROIMAGE
LA English
DT Article
DE Working memory; Aging; fMRI; Functional connectivity; Caudate;
Prefrontal cortex
ID BASAL-GANGLIA; CONVERGING EVIDENCE; BRAIN ACTIVATION; OLDER-ADULTS;
COGNITION; DOPAMINE; CONNECTIVITY; INHIBITION; CEREBELLUM; MODULATION
AB Normal aging is associated with a gradual decline in executive functions such as set-shifting, inhibition, and updating, along with a progressive decline of neurotransmitter systems including the dopamine system. Modulation from the dopamine system is thought to be critical for the gating of information during working memory. Given the known relationships between executive aging, cognition, and dopamine, this study aims to explore the neurobiology underlying age-related changes in working memory updating using fMRI with healthy subjects from across the adult age spectrum. Our results indicate that older age is associated with poorer performance, reduced meso-cortico-striatal activation, and reduced functional coupling between the caudate and the VLPFC during the updating task. Additionally, caudate activation is associated with improved accuracy and VLPFC activation with faster reaction times in the full sample. Thus, older subjects' under-recruitment of and reduced functional coupling between these regions may specifically underlie age-related changes in working memory updating. These results are consistent with computational models of executive cognition and dopamine-mediated age-related cognitive decline. (c) 2012 Elsevier Inc. All rights reserved.
C1 [Weinberger, Daniel R.; Mattay, Venkata S.] Lieber Inst Brain Dev, Baltimore, MD 21205 USA.
[Sambataro, Fabio] Ist Italiano Tecnol UNIPr, Brain Ctr Motor & Social Cognit, Parma, Italy.
[Podell, Jamie E.; Sambataro, Fabio; Murty, Vishnu P.; Emery, Matthew R.; Tong, Yunxia; Das, Saumitra; Goldberg, Terry E.; Weinberger, Daniel R.; Mattay, Venkata S.] NIMH, Clin Brain Disorders Branch, Genes Cognit & Psychosis Program, Intramural Res Program,NIH, Bethesda, MD 20892 USA.
RP Mattay, VS (reprint author), Lieber Inst Brain Dev, Johns Hopkins Med Campus,855 N Wolfe St, Baltimore, MD 21205 USA.
EM anand.mattay@libd.org
RI Sambataro, Fabio/E-3426-2010
OI Sambataro, Fabio/0000-0003-2102-416X
FU National Institute of Mental Health Intramural Research Program
FX We would like to thank Martin Safrin and Kristina Thurin for their
assistance with fMRI data collection and Bradley Zoltick for his help
with performance data parsing. This work was supported by the National
Institute of Mental Health Intramural Research Program, and the study
protocol was approved by the Intramural Review Board of the National
Institute of Mental Health.
NR 54
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U1 2
U2 18
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1053-8119
J9 NEUROIMAGE
JI Neuroimage
PD SEP
PY 2012
VL 62
IS 3
BP 2151
EP 2160
DI 10.1016/j.neuroimage.2012.05.066
PG 10
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 986TR
UT WOS:000307369000079
PM 22659476
ER
PT J
AU Yao, B
Li, TQ
van Gelderen, P
Shmueli, K
de Zwart, JA
Duyn, JH
AF Yao, Bing
Li, Tie-Qiang
van Gelderen, Peter
Shmueli, Karin
de Zwart, Jacco A.
Duyn, Jeff H.
TI Susceptibility contrast in high field MRI of human brain as a function
of tissue iron content (vol 44, pg 1259, 2009)
SO NEUROIMAGE
LA English
DT Correction
C1 [Yao, Bing; Li, Tie-Qiang; van Gelderen, Peter; Shmueli, Karin; de Zwart, Jacco A.; Duyn, Jeff H.] NINDS, Adv MRI Sect, Lab Funct Mol Imaging, NIH, Bethesda, MD 20892 USA.
RP Yao, B (reprint author), NINDS, Adv MRI Sect, Lab Funct Mol Imaging, NIH, 10 Ctr Dr,Bldg 10,Room B1D728, Bethesda, MD 20892 USA.
EM yaob@mail.nih.gov
RI Shmueli, Karin/B-9432-2017
NR 1
TC 0
Z9 0
U1 0
U2 7
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1053-8119
J9 NEUROIMAGE
JI Neuroimage
PD SEP
PY 2012
VL 62
IS 3
BP 2173
EP 2173
DI 10.1016/j.nueroimage.2012.03.055
PG 1
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 986TR
UT WOS:000307369000083
ER
PT J
AU Rothman, SM
Mattson, MP
AF Rothman, Sarah M.
Mattson, Mark P.
TI Sleep Disturbances in Alzheimer's and Parkinson's Diseases
SO NEUROMOLECULAR MEDICINE
LA English
DT Review
DE Alzheimer's disease; Parkinson's disease; Sleep; Circadian
ID EYE-MOVEMENT SLEEP; TRANSGENIC MOUSE MODEL; SLOW-WAVE SLEEP; BEHAVIOR
DISORDER; REM-SLEEP; DOPAMINERGIC-NEURONS; PARADOXICAL SLEEP; BASAL
FOREBRAIN; LEWY BODIES; VOLUNTARY EXERCISE
AB Alzheimer's disease (AD) and Parkinson's disease (PD) are the two most common neurodegenerative disorders and exact a burden on our society greater than cardiovascular disease and cancer combined. While cognitive and motor symptoms are used to define AD and PD, respectively, patients with both disorders exhibit sleep disturbances including insomnia, hypersomnia and excessive daytime napping. The molecular basis of perturbed sleep in AD and PD may involve damage to hypothalamic and brainstem nuclei that control sleep-wake cycles. Perturbations in neurotransmitter and hormone signaling (e.g., serotonin, norepinephrine and melatonin) and the neurotrophic factor BDNF likely contribute to the disease process. Abnormal accumulations of neurotoxic forms of amyloid beta-peptide, tau and alpha-synuclein occur in brain regions involved in the regulation of sleep in AD and PD patients, and are sufficient to cause sleep disturbances in animal models of these neurodegenerative disorders. Disturbed regulation of sleep often occurs early in the course of AD and PD, and may contribute to the cognitive and motor symptoms. Treatments that target signaling pathways that control sleep have been shown to retard the disease process in animal models of AD and PD, suggesting a potential for such interventions in humans at risk for or in the early stages of these disorders.
C1 [Rothman, Sarah M.; Mattson, Mark P.] NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA.
RP Rothman, SM (reprint author), NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA.
EM rothmansm@mail.nih.gov
FU NIH, National Institute on Aging
FX This research was supported entirely by the Intramural Research Program
of the NIH, National Institute on Aging.
NR 134
TC 30
Z9 34
U1 4
U2 54
PU HUMANA PRESS INC
PI TOTOWA
PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA
SN 1535-1084
EI 1559-1174
J9 NEUROMOL MED
JI Neuromol. Med.
PD SEP
PY 2012
VL 14
IS 3
BP 194
EP 204
DI 10.1007/s12017-012-8181-2
PG 11
WC Neurosciences
SC Neurosciences & Neurology
GA 988WJ
UT WOS:000307521200005
PM 22552887
ER
PT J
AU Rianon, NJ
Lang, TF
Sigurdsson, G
Eiriksdottir, G
Sigurdsson, S
Garcia, M
Pajala, S
Koster, A
Yu, B
Selwyn, BJ
Taylor, WC
Kapadia, AS
Gudnason, V
Launer, LJ
Harris, TB
AF Rianon, N. J.
Lang, T. F.
Sigurdsson, G.
Eiriksdottir, G.
Sigurdsson, S.
Garcia, M.
Pajala, S.
Koster, A.
Yu, B.
Selwyn, B. J.
Taylor, W. C.
Kapadia, A. S.
Gudnason, V.
Launer, L. J.
Harris, T. B.
TI Lifelong physical activity in maintaining bone strength in older men and
women of the Age, Gene/Environment Susceptibility-Reykjavik Study
SO OSTEOPOROSIS INTERNATIONAL
LA English
DT Article
DE AGES-Reykjavik Study; Bone mineral density; Older men and women;
Osteoporosis; Physical activity; QCT bone measures
ID MINERAL DENSITY; POSTMENOPAUSAL WOMEN; VOLUMETRIC BMD; EXERCISE;
PARTICIPATION; HIP; PREDICTION; FRACTURE; SPORT; SPINE
AB We examined if lifelong physical activity is important for maintaining bone strength in the elderly. Associations of quantitative computerized tomography-acquired bone measures (vertebral and femoral) and self-reported physical activity in mid-life (mean age, 50 years), in old age (a parts per thousand yen65 years), and throughout life (recalled during old age) were investigated in 2,110 men and 2,682 women in the AGES-Reykjavik Study. Results conclude lifelong physical activity with continuation into old age (a parts per thousand yen65 years) best maintains better bone health later in life.
Skeletal loading is thought to modulate the loss of bone in later life, and physical activity is a chief means of affecting bone strength by skeletal loading. Despite much discussion regarding lifelong versus early adulthood physical activity for preventing bone loss later in life, inconsistency still exists regarding how to maintain bone mass later in life (a parts per thousand yen65 years).
We examined if lifelong physical activity is important for maintaining bone strength in the elderly.
The associations of quantitative computerized tomography-acquired vertebral and femoral bone measures and self-reported physical activity in mid-life (mean age, 50 years), in old age (a parts per thousand yen65 years), and throughout life (recalled during old age) were investigated in 2,110 men and 2,682 women in the AGES-Reykjavik Study.
Our findings conclude that lifelong physical activity with continuation into old age (a parts per thousand yen65 years) best maintains better bone health in the elderly.
C1 [Rianon, N. J.] UTHSC Med Sch, Houston, TX 77030 USA.
[Lang, T. F.] UCSF Sch Med, San Francisco, CA USA.
[Sigurdsson, G.] Landspitali Univ Hosp, Dept Internal Med, Div Endocrinol & Metab, Reykjavik, Iceland.
[Eiriksdottir, G.; Sigurdsson, S.; Gudnason, V.] Iceland Heart Assoc, Kopavogur, Iceland.
[Garcia, M.; Koster, A.; Yu, B.; Harris, T. B.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA.
[Pajala, S.] Natl Inst Hlth & Welf, Helsinki, Finland.
[Selwyn, B. J.; Taylor, W. C.; Kapadia, A. S.] UTHSC Sch Publ Hlth, Houston, TX USA.
[Gudnason, V.] Univ Iceland, Reykjavik, Iceland.
[Launer, L. J.] NIA, Neuroepidemiol Sect, Bethesda, MD 20892 USA.
RP Rianon, NJ (reprint author), UTHSC Med Sch, 6431 Fannin JJL324, Houston, TX 77030 USA.
EM Nahid.J.Rianon@uth.tmc.edu
RI Koster, Annemarie/E-7438-2010; Lang, Thomas/B-2685-2012; Gudnason,
Vilmundur/K-6885-2015
OI Lang, Thomas/0000-0002-3720-8038; Gudnason,
Vilmundur/0000-0001-5696-0084
FU NIH [N01-AG-12100]; NIA Intramural Research Program, Hjartavernd (the
Icelandic Heart Association); Althingi (the Icelandic Parliament)
FX The Age, Gene/Environment Susceptibility-Reykjavik Study is funded by
NIH contract N01-AG-12100, the NIA Intramural Research Program,
Hjartavernd (the Icelandic Heart Association), and the Althingi (the
Icelandic Parliament). Genotyping was conducted at the NIA IRP
Laboratory of Neurogenetics.
NR 27
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Z9 4
U1 0
U2 13
PU SPRINGER LONDON LTD
PI LONDON
PA 236 GRAYS INN RD, 6TH FLOOR, LONDON WC1X 8HL, ENGLAND
SN 0937-941X
J9 OSTEOPOROSIS INT
JI Osteoporosis Int.
PD SEP
PY 2012
VL 23
IS 9
BP 2303
EP 2312
DI 10.1007/s00198-011-1874-9
PG 10
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 991RA
UT WOS:000307717700006
PM 22234811
ER
PT J
AU Sarangi, PP
Hyun, YM
Lerman, YV
Pietropaoli, AP
Kim, M
AF Sarangi, Pranita P.
Hyun, Young-Min
Lerman, Yelena V.
Pietropaoli, Anthony P.
Kim, Minsoo
TI ROLE OF beta(1) INTEGRIN IN TISSUE HOMING OF NEUTROPHILS DURING SEPSIS
SO SHOCK
LA English
DT Article
DE Neutrophils; integrin beta(1); sepsis; infiltration
ID PULMONARY INFLAMMATION; ACTIVATION; EXPRESSION; MICE; INTERLEUKIN-8;
RECRUITMENT; INHIBITION; MIGRATION; PATHWAYS; ELASTASE
AB Aberrant activation of neutrophils during sepsis results in the widespread release of proinflammatory mediators, leading to multiorgan system failure and death. However, aberrant activation of neutrophils during sepsis results in the widespread release of harmful inflammatory mediators causing host tissue injuries that can lead to multiorgan system failure and death. One of the pivotal components of neutrophil migration during inflammation is the expression of surface integrins. In this study, we show that administration of a cyclic analog of RGD peptide (Arg-Gly-Asp) significantly reduced the number of tissue-invading neutrophils and the degree of sepsis-induced lethality in mice as compared with control peptide. Second, beta(1) integrin (CD29) was highly upregulated on the neutrophils isolated from both septic patients and animals. Finally, conditional genetic ablation of beta(1) integrin from granulocytes also improved survival and bacterial clearance in septic animals Thus, our results indicate that expression of beta(1) integrin is important for modulating neutrophil trafficking during sepsis and that therapeutics designed against beta(1) integrins may be beneficial.
C1 [Kim, Minsoo] Univ Rochester, Dept Microbiol & Immunol, David H Smith Ctr Vaccine Biol & Immunol, Med Ctr, Rochester, NY 14642 USA.
[Lerman, Yelena V.] Univ Rochester, Dept Physiol & Pharmacol, Rochester, NY 14642 USA.
[Pietropaoli, Anthony P.] Univ Rochester, Pulm & Crit Care Med Div, Rochester, NY 14642 USA.
RP Sarangi, PP (reprint author), NIDCR, Lab Cell & Dev Biol, NIH, 30 Convent Dr,Room 432, Bethesda, MD 20892 USA.
EM sarangipp@mail.nih.gov; Minsoo_Kim@urmc.rochester.edu
FU NIH [HL087088, HL018208, HL094797, DA007232]
FX This project was supported by NIH HL087088 (M.K.), NIH HL018208 (M.K.),
NIH HL094797 (M.K.), and NIH DA007232 (Y.V.L.).
NR 34
TC 5
Z9 6
U1 0
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1073-2322
EI 1540-0514
J9 SHOCK
JI Shock
PD SEP
PY 2012
VL 38
IS 3
BP 281
EP 287
DI 10.1097/SHK.0b013e31826136f8
PG 7
WC Critical Care Medicine; Hematology; Surgery; Peripheral Vascular Disease
SC General & Internal Medicine; Hematology; Surgery; Cardiovascular System
& Cardiology
GA 990KC
UT WOS:000307628400008
PM 22683734
ER
PT J
AU Lampl, M
Lee, W
Koo, W
Frongillo, EA
Barker, DJP
Romero, R
AF Lampl, Michelle
Lee, Wesley
Koo, Winston
Frongillo, Edward A.
Barker, David J. P.
Romero, Roberto
TI Ethnic differences in the accumulation of fat and lean mass in late
gestation
SO AMERICAN JOURNAL OF HUMAN BIOLOGY
LA English
DT Article
ID RESTING ENERGY-EXPENDITURE; CORONARY-HEART-DISEASE; AIR-DISPLACEMENT
PLETHYSMOGRAPHY; SOUTHEASTERN UNITED-STATES; STAGE RENAL-DISEASE;
BODY-COMPOSITION; AFRICAN-AMERICANS; PRETERM BIRTH; IN-UTERO;
METABOLIC-RATE
AB Objectives: Lower birth weight within the normal range predicts adult chronic diseases, but the same birth weight in different ethnic groups may reflect different patterns of tissue development. Neonatal body composition was investigated among non-Hispanic Caucasians and African Americans, taking advantage of variability in gestational duration to understand growth during late gestation. Methods: Air displacement plethysmography assessed fat and lean body mass among 220 non-Hispanic Caucasian and 93 non-Hispanic African American neonates. The two ethnic groups were compared using linear regression. Results: At 36 weeks of gestation, the average lean mass of Caucasian neonates was 2,515 g vs. that of 2,319 g of African American neonates (difference, P = 0.02). The corresponding figures for fat mass were 231 and 278 g, respectively (difference, P = 0.24). At 41 weeks, the Caucasians were 319 g heavier in lean body mass (P < 0.001) but were also 123 g heavier in fat mass (P = 0.001). The slopes for lean mass vs. gestational week were similar, but the slope of fat mass was 5.8 times greater (P = 0.009) for Caucasian (41.0 g/week) than for African American neonates (7.0 g/week). Conclusions: By 36 weeks of gestation, the African American fetus developed similar fat mass and less lean mass compared with the Caucasian fetus. Thereafter, changes in lean mass among the African American fetus with increasing gestational age at birth were similar to the Caucasian fetus, but fat accumulated more slowly. We hypothesize that different ethnic fetal growth strategies involving body composition may contribute to ethnic health disparities in later life. Am. J. Hum. Biol. 2012. (c) 2012 Wiley Periodicals, Inc.
C1 [Lampl, Michelle] Emory Univ, Dept Anthropol, Ctr Study Human Hlth, Atlanta, GA 30322 USA.
[Lee, Wesley] Oakland Univ, William Beaumont Sch Med, Dept Obstet & Gynecol, Rochester, MI USA.
[Lee, Wesley; Romero, Roberto] Eunice Kennedy Shriver Natl Inst Child Hlth & Dev, Perinatol Res Branch, NIH, DHHS Bethesda, Bethesda, MD USA.
[Koo, Winston] Wayne State Univ, Sch Med, Carman & Ann Adams Dept Pediat, Detroit, MI USA.
[Frongillo, Edward A.] Univ S Carolna, Dept Hlth Promot Educ & Behav, Columbia, SC USA.
[Barker, David J. P.] Univ Southampton, Southampton Gen Hosp, MRC Lifecourse Epidemiol Unit, Southampton, Hants, England.
[Romero, Roberto] Wayne State Univ, Sch Med, Ctr Mol Med & Genet, Detroit, MI USA.
RP Lampl, M (reprint author), Emory Univ, Dept Anthropol, Ctr Study Human Hlth, 107 Candler Lib, Atlanta, GA 30322 USA.
EM mlampl@emory.edu
RI Lampl, Michelle/B-1619-2013
FU Perinatology Research Branch, Division of Intramural Research, Eunice
Kennedy Shriver National Institute of Child Health and Human
Development, NIH, DHHS
FX Contract grant sponsor: Perinatology Research Branch, Division of
Intramural Research, Eunice Kennedy Shriver National Institute of Child
Health and Human Development, NIH, DHHS.
NR 69
TC 8
Z9 8
U1 0
U2 6
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1042-0533
J9 AM J HUM BIOL
JI Am. J. Hum. Biol.
PD SEP-OCT
PY 2012
VL 24
IS 5
BP 640
EP 647
DI 10.1002/ajhb.22285
PG 8
WC Anthropology; Biology
SC Anthropology; Life Sciences & Biomedicine - Other Topics
GA 986WV
UT WOS:000307377800009
PM 22565933
ER
PT J
AU Collin, N
Assumpcao, TCF
Mizurini, DM
Gilmore, DC
Dutra-Oliveira, A
Kotsyfakis, M
Sa-Nunes, A
Teixeira, C
Ribeiro, JMC
Monteiro, RQ
Valenzuela, JG
Francischetti, IMB
AF Collin, Nicolas
Assumpcao, Teresa C. F.
Mizurini, Daniella M.
Gilmore, Dana C.
Dutra-Oliveira, Angelica
Kotsyfakis, Michalis
Sa-Nunes, Anderson
Teixeira, Clarissa
Ribeiro, Jose M. C.
Monteiro, Robson Q.
Valenzuela, Jesus G.
Francischetti, Ivo M. B.
TI Lufaxin, a Novel Factor Xa Inhibitor From the Salivary Gland of the Sand
Fly Lutzomyia longipalpis Blocks Protease-Activated Receptor 2
Activation and Inhibits Inflammation and Thrombosis In Vivo
SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
LA English
DT Article
DE hematophagy; leishmaniasis; microcirculation; thrombosis; vector biology
ID COAGULATION-FACTOR-XA; ANTICOAGULANT PEPTIDE; PLATELET-AGGREGATION;
BLOOD-COAGULATION; TISSUE FACTOR; HEMATOPHAGOUS ANIMALS;
ANCYLOSTOMA-CANINUM; IXODES-SCAPULARIS; ARTHROPOD SALIVA; BREAST-CANCER
AB Objective-Blood-sucking arthropods' salivary glands contain a remarkable diversity of antihemostatics. The aim of the present study was to identify the unique salivary anticoagulant of the sand fly Lutzomyia longipalpis, which remained elusive for decades.
Methods and Results-Several L. longipalpis salivary proteins were expressed in human embryonic kidney 293 cells and screened for inhibition of blood coagulation. A novel 32.4-kDa molecule, named Lufaxin, was identified as a slow, tight, noncompetitive, and reversible inhibitor of factor Xa (FXa). Notably, Lufaxin's primary sequence does not share similarity to any physiological or salivary inhibitors of coagulation reported to date. Lufaxin is specific for FXa and does not interact with FX, Dansyl-Glu-Gly-Arg-FXa, or 15 other enzymes. In addition, Lufaxin blocks prothrombinase and increases both prothrombin time and activated partial thromboplastin time. Surface plasmon resonance experiments revealed that FXa binds Lufaxin with an equilibrium constant approximate to 3 nM, and isothermal titration calorimetry determined a stoichiometry of 1:1. Lufaxin also prevents protease-activated receptor 2 activation by FXa in the MDA-MB-231 cell line and abrogates edema formation triggered by injection of FXa in the paw of mice. Moreover, Lufaxin prevents FeCl3-induced carotid artery thrombus formation and prolongs activated partial thromboplastin time ex vivo, implying that it works as an anticoagulant in vivo. Finally, salivary gland of sand flies was found to inhibit FXa and to interact with the enzyme.
Conclusion-Lufaxin belongs to a novel family of slow-tight FXa inhibitors, which display antithrombotic and anti-inflammatory activities. It is a useful tool to understand FXa structural features and its role in prohemostatic and proinflammatory events. (Arterioscler Thromb Vasc Biol. 2012;32:2185-2196.)
C1 [Collin, Nicolas; Gilmore, Dana C.; Teixeira, Clarissa; Valenzuela, Jesus G.] NIAID, Vector Mol Biol Sect, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA.
[Collin, Nicolas] Univ Lausanne, Dept Biochem, Vaccine Formulat Lab, CH-1066 Epalinges, Switzerland.
[Assumpcao, Teresa C. F.; Ribeiro, Jose M. C.; Francischetti, Ivo M. B.] NIAID, Vector Biol Sect, LMVR, NIH, Bethesda, MD 20892 USA.
[Mizurini, Daniella M.; Dutra-Oliveira, Angelica; Monteiro, Robson Q.] Univ Fed Rio de Janeiro, Inst Bioquim Med, Rio De Janeiro, Brazil.
[Kotsyfakis, Michalis] Acad Sci Czech Republic, Inst Parasitol, Ctr Biol, CR-37005 Ceske Budejovice, Czech Republic.
[Sa-Nunes, Anderson] Univ Sao Paulo, Inst Ciencias Biomed, Dept Imunol, BR-05508 Sao Paulo, Brazil.
RP Francischetti, IMB (reprint author), NIAID, Vector Mol Biol Sect, Lab Malaria & Vector Res, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM jvalenzuela@niaid.nih.gov; ifrancischetti@niaid.nih.gov
RI Sa-Nunes, Anderson/D-8667-2012; Inbeb, Inct/K-2317-2013; Monteiro,
Robson/B-8007-2014; Kotsyfakis, Michail/G-9525-2014; Ribeiro,
Jose/J-7011-2015;
OI Sa-Nunes, Anderson/0000-0002-1859-4973; Kotsyfakis,
Michail/0000-0002-7526-1876; Ribeiro, Jose/0000-0002-9107-0818
FU Intramural Research Program of the Division of Intramural Research,
National Institute of Allergy and Infectious Diseases, National
Institutes of Health (NIH; Bethesda, MD); Conselho Nacional de
Desenvolvimento Cientifico e Tecnologico (CNPq); Fundacao de Amparo a
Pesquisa do Estado do Rio de Janeiro Carlos Chagas Filho (FAPERJ);
Fundacao do Cancer and Coordenacao de Aperfeicoamento de Pessoal de
Nivel Superior (CAPES); Grant Agency of the Czech Republic
[P502/12/2409]; National Academy of Sciences of the Czech Republic;
Marie Curie Reintegration grant of the EU-FP7 [PIRG07-GA-2010-268177]
FX This work was supported by the Intramural Research Program of the
Division of Intramural Research, National Institute of Allergy and
Infectious Diseases, National Institutes of Health (NIH; Bethesda, MD).
R.Q. Monteiro received a grant from Conselho Nacional de Desenvolvimento
Cientifico e Tecnologico (CNPq), Fundacao de Amparo a Pesquisa do Estado
do Rio de Janeiro Carlos Chagas Filho (FAPERJ), Fundacao do Cancer and
Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES). M.
Kotsyfakis received support from grant number P502/12/2409 of the Grant
Agency of the Czech Republic, from a Jan Evangelista Purkyne fellowship
of the National Academy of Sciences of the Czech Republic, and from a
Marie Curie Reintegration grant of the EU-FP7 (PIRG07-GA-2010-268177).
Because Drs Francischetti, Valenzuela, and Ribeiro are government
employees, and this is a government work, the work is in the public
domain in the United States. Notwithstanding any other agreements, the
NIH reserves the right to provide the work to PubMedCentral for display
and use by the public, and PubMedCentral may tag or modify the work
consistent with its customary practices. You can establish rights
outside of the United States subject to a government use license.
NR 50
TC 28
Z9 28
U1 0
U2 8
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1079-5642
J9 ARTERIOSCL THROM VAS
JI Arterioscler. Thromb. Vasc. Biol.
PD SEP
PY 2012
VL 32
IS 9
BP 2185
EP +
DI 10.1161/ATVBAHA.112.253906
PG 28
WC Hematology; Peripheral Vascular Disease
SC Hematology; Cardiovascular System & Cardiology
GA 992JZ
UT WOS:000307773100021
PM 22796577
ER
PT J
AU Little, AC
Paukner, A
Woodward, RA
Suomi, SJ
AF Little, Anthony C.
Paukner, Annika
Woodward, Ruth A.
Suomi, Stephen J.
TI Facial asymmetry is negatively related to condition in female macaque
monkeys
SO BEHAVIORAL ECOLOGY AND SOCIOBIOLOGY
LA English
DT Article
DE Health; Asymmetry; Sexual selection; Quality; Measurements
ID CONDITION SCORING SYSTEM; FLUCTUATING ASYMMETRY; DEVELOPMENTAL
STABILITY; SEXUAL-DIMORPHISM; MACACA-MULATTA; RHESUS MACAQUES; HUMAN
FACES; GOOD GENES; SYMMETRY; ATTRACTIVENESS
AB The face is an important visual trait in social communication across many species. In evolutionary terms, there are large and obvious selective advantages in detecting healthy partners, both in terms of avoiding individuals with poor health to minimise contagion and in mating with individuals with high health to help ensure healthy offspring. Many models of sexual selection suggest that an individual's phenotype provides cues to their quality. Fluctuating asymmetry is a trait that is proposed to be an honest indicator of quality, and previous studies have demonstrated that rhesus monkeys gaze longer at symmetric faces, suggesting preferences for such faces. The current study examined the relationship between measured facial symmetry and measures of health in a captive population of female rhesus macaque monkeys. We measured asymmetry from landmarks marked on front-on facial photographs and computed measures of health based on veterinary health and condition ratings, number of minor and major wounds sustained and gain in weight over the first 4 years of life. Analysis revealed that facial asymmetry was negatively related to condition-related health measures, with symmetric individuals being healthier than more asymmetric individuals. Facial asymmetry appears to be an honest indicator of health in rhesus macaques, and asymmetry may then be used by conspecifics in mate-choice situations. More broadly, our data support the notion that faces are valuable sources of information in non-human primates and that sexual selection based on facial information is potentially important across the primate lineage.
C1 [Little, Anthony C.] Univ Stirling, Sch Nat Sci, Stirling FK9 4LA, Scotland.
[Paukner, Annika; Suomi, Stephen J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Comparat Ethol Lab, US Dept HHS, NIH, Poolesville, MD USA.
[Woodward, Ruth A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, US Dept HHS, Res Anim Management Branch, NIH, Poolesville, MD USA.
RP Little, AC (reprint author), Univ Stirling, Sch Nat Sci, Stirling FK9 4LA, Scotland.
EM anthony.little@stir.ac.uk
RI Little, Anthony/B-8497-2009
OI Little, Anthony/0000-0001-9100-1903
FU Royal Society University Research Fellowship; Division of Intramural
Research, NICHD
FX Anthony Little is supported by a Royal Society University Research
Fellowship. This research was supported by the Division of Intramural
Research, NICHD.
NR 38
TC 4
Z9 4
U1 1
U2 42
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0340-5443
J9 BEHAV ECOL SOCIOBIOL
JI Behav. Ecol. Sociobiol.
PD SEP
PY 2012
VL 66
IS 9
BP 1311
EP 1318
DI 10.1007/s00265-012-1386-4
PG 8
WC Behavioral Sciences; Ecology; Zoology
SC Behavioral Sciences; Environmental Sciences & Ecology; Zoology
GA 988SI
UT WOS:000307510600013
PM 23667290
ER
PT J
AU Saporito, RA
Donnelly, MA
Spande, TF
Garraffo, HM
AF Saporito, Ralph A.
Donnelly, Maureen A.
Spande, Thomas F.
Garraffo, H. Martin
TI A review of chemical ecology in poison frogs
SO CHEMOECOLOGY
LA English
DT Review
DE Ants; Bufonids; Chemical defense; Dendrobatids; Mantellids;
Melanophryniscus; Oribatid mites; Pseudophryne; Sequestration
ID BUFONID TOADS MELANOPHRYNISCUS; DENDROBATES-PUMILIO;
GEOGRAPHIC-VARIATION; SKIN ALKALOIDS; DART FROGS; PYRROLIZIDINE
ALKALOIDS; CONVERGENT EVOLUTION; DIET SPECIALIZATION; ARTHROPOD SOURCE;
OOPHAGA-PUMILIO
AB Herein we review what is known about the chemical ecology of poison frogs with a focus on dendrobatid poison frogs. While five anuran families are known to have an alkaloid-derived chemical defense, the dendrobatids have been studied in greatest detail and provides chemical ecologists with a complex model system for understanding how chemical defenses operate in real time and may have evolved through evolutionary time. We describe the diversity of alkaloid defenses known from frogs, alkaloid sequestration, biosynthesis and modification, and we review what is known concerning arthropod sources for alkaloids. There is variation in nearly every attribute of the system and we try to describe some of the challenges associated with unraveling the complexities of this model system.
C1 [Saporito, Ralph A.] John Carroll Univ, Dept Biol, University Hts, OH 44118 USA.
[Donnelly, Maureen A.] Florida Int Univ, Coll Arts & Sci, Miami, FL 33199 USA.
[Spande, Thomas F.; Garraffo, H. Martin] NIDDK, Bioorgan Chem Lab, DHHS, NIH, Bethesda, MD 20892 USA.
RP Saporito, RA (reprint author), John Carroll Univ, Dept Biol, University Hts, OH 44118 USA.
EM ralph.saporito@gmail.com
FU Environmental Protection Agency; Florida International University;
National Geographic Society; National Institute of Diabetes and
Digestive and Kidney Diseases; National Institutes of Health;
Organization for Tropical Studies; Smithsonian Tropical Research
Institute; National Science Foundation [IOS-0813842]
FX This paper is dedicated to the memory of our friend and colleague John
W. Daly, whose pioneering research founded and continues to inspire the
study of poison frog chemical ecology. We would also like to acknowledge
his life-long colleague, C. W. Myers (Curator Emeritus, Department of
Herpetology, American Museum of Natural History), who collaborated
extensively with John over the past 40 years on the study of poison
frogs. We thank Tappey H. Jones (Virginia Military Institute), who
collaborated with John in the identification and synthesis of ant
alkaloids. We also thank Richard L. Hoffman (Virginia Museum of Natural
History), John T. Longino (Evergreen State College), and Roy A. Norton
(State University of New York, Syracuse) for their assistance in
identifying many of the alkaloid-containing arthropods. We are grateful
to Alan H. Savitzky and Jenise M. Snyder for providing valuable comments
that improved the quality of this manuscript. We would like to thank the
Environmental Protection Agency, Florida International University,
National Geographic Society, National Institute of Diabetes and
Digestive and Kidney Diseases, National Institutes of Health,
Organization for Tropical Studies, and Smithsonian Tropical Research
Institute for their generous funding. A National Science Foundation
Postdoctoral Research Fellowship partially supported R. A. S. This work
is derived from a presentation in the symposium "Sequestered Defensive
Compounds in Tetrapod Vertebrates: A Symposium in Memory of John W.
Daly," held at the Sixth World Congress of Herpetology in Manaus,
Brazil, on 21 August 2008 and supported by NSF IOS-0813842.
NR 84
TC 48
Z9 49
U1 13
U2 128
PU SPRINGER BASEL AG
PI BASEL
PA PICASSOPLATZ 4, BASEL, 4052, SWITZERLAND
SN 0937-7409
EI 1423-0445
J9 CHEMOECOLOGY
JI Chemoecology
PD SEP
PY 2012
VL 22
IS 3
BP 159
EP 168
DI 10.1007/s00049-011-0088-0
PG 10
WC Biochemistry & Molecular Biology; Ecology
SC Biochemistry & Molecular Biology; Environmental Sciences & Ecology
GA 988TB
UT WOS:000307512500003
ER
PT J
AU Abnet, C
AF Abnet, C.
TI Linxian China: A Population with High Incidence of Esophageal Cancer and
Multiple Adverse Exposures
SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS
LA English
DT Meeting Abstract
CT 43rd Annual Meeting of the Environmental-Mutagen-Society (EMS)
CY SEP 08-12, 2012
CL Bellevue, WA
SP Environm Mutagen Soc (EMS)
C1 [Abnet, C.] NCI, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0893-6692
J9 ENVIRON MOL MUTAGEN
JI Environ. Mol. Mutagen.
PD SEP
PY 2012
VL 53
SU 1
BP S23
EP S23
PG 1
WC Environmental Sciences; Genetics & Heredity; Toxicology
SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology
GA 993YM
UT WOS:000307896300045
ER
PT J
AU Attene-Ramos, M
Huang, R
Sakamuru, S
Witt, K
Tice, R
Austin, C
Xia, M
AF Attene-Ramos, M.
Huang, R.
Sakamuru, S.
Witt, K.
Tice, R.
Austin, C.
Xia, M.
TI Toxicity Assessment of Environmental Chemicals Using a Quantitative
High-Throughput Screening Approach
SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS
LA English
DT Meeting Abstract
CT 43rd Annual Meeting of the Environmental-Mutagen-Society (EMS)
CY SEP 08-12, 2012
CL Bellevue, WA
SP Environm Mutagen Soc (EMS)
C1 [Attene-Ramos, M.; Huang, R.; Sakamuru, S.; Austin, C.; Xia, M.] NIH, Chem Genom Ctr, NCATS, Bethesda, MD 20892 USA.
[Witt, K.; Tice, R.] NIEHS, DNTP, Res Triangle Pk, NC 27709 USA.
NR 0
TC 0
Z9 0
U1 1
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0893-6692
J9 ENVIRON MOL MUTAGEN
JI Environ. Mol. Mutagen.
PD SEP
PY 2012
VL 53
SU 1
BP S29
EP S29
PG 1
WC Environmental Sciences; Genetics & Heredity; Toxicology
SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology
GA 993YM
UT WOS:000307896300069
ER
PT J
AU Butler, K
Rajani, A
Elespuru, R
AF Butler, K.
Rajani, A.
Elespuru, R.
TI Genotoxicity and Uptake of Titanium Dioxide Nanoparticles in Salmonella
typhimurium
SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS
LA English
DT Meeting Abstract
CT 43rd Annual Meeting of the Environmental-Mutagen-Society (EMS)
CY SEP 08-12, 2012
CL Bellevue, WA
SP Environm Mutagen Soc (EMS)
C1 [Butler, K.] NCI, Bethesda, MD 20892 USA.
[Butler, K.; Rajani, A.; Elespuru, R.] US FDA, Silver Spring, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0893-6692
J9 ENVIRON MOL MUTAGEN
JI Environ. Mol. Mutagen.
PD SEP
PY 2012
VL 53
SU 1
BP S58
EP S58
PG 1
WC Environmental Sciences; Genetics & Heredity; Toxicology
SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology
GA 993YM
UT WOS:000307896300184
ER
PT J
AU Gorospe, M
AF Gorospe, M.
TI Regulation of HuR Function by Stress-Response Kinases
SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS
LA English
DT Meeting Abstract
CT 43rd Annual Meeting of the Environmental-Mutagen-Society (EMS)
CY SEP 08-12, 2012
CL Bellevue, WA
SP Environm Mutagen Soc (EMS)
C1 [Gorospe, M.] NIH, NIA IRP, Baltimore, MD USA.
NR 0
TC 1
Z9 1
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0893-6692
J9 ENVIRON MOL MUTAGEN
JI Environ. Mol. Mutagen.
PD SEP
PY 2012
VL 53
SU 1
BP S19
EP S19
PG 1
WC Environmental Sciences; Genetics & Heredity; Toxicology
SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology
GA 993YM
UT WOS:000307896300029
ER
PT J
AU Hobbs, CA
Morgan, DL
Shepard, K
Price, HC
Kissling, GE
Shockley, KR
Recio, L
Witt, KL
French, JE
AF Hobbs, C. A.
Morgan, D. L.
Shepard, K.
Price, H. C.
Kissling, G. E.
Shockley, K. R.
Recio, L.
Witt, K. L.
French, J. E.
TI Population Variation in Micronucleus Response to Inhaled Benzene in
Diversity Outbred (J:DO) Mice
SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS
LA English
DT Meeting Abstract
CT 43rd Annual Meeting of the Environmental-Mutagen-Society (EMS)
CY SEP 08-12, 2012
CL Bellevue, WA
SP Environm Mutagen Soc (EMS)
C1 [Hobbs, C. A.; Shepard, K.; Recio, L.] Integrated Lab Syst Inc, Genet & Mol Toxicol Div, Res Triangle Pk, NC USA.
[Price, H. C.] Alion Sci & Technol, Life Sci & Inhalat Toxicol Lab, Res Triangle Pk, NC USA.
[Morgan, D. L.; Kissling, G. E.; Shockley, K. R.; Witt, K. L.; French, J. E.] NIEHS, Div Natl Toxicol Program, Res Triangle Pk, NC 27709 USA.
NR 0
TC 0
Z9 0
U1 0
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0893-6692
J9 ENVIRON MOL MUTAGEN
JI Environ. Mol. Mutagen.
PD SEP
PY 2012
VL 53
SU 1
BP S26
EP S26
PG 1
WC Environmental Sciences; Genetics & Heredity; Toxicology
SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology
GA 993YM
UT WOS:000307896300057
ER
PT J
AU Martin, WJ
AF Martin, W. J., II
TI Household Air Pollution: A Preventable Cause of Two Million Deaths
Annually
SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS
LA English
DT Meeting Abstract
CT 43rd Annual Meeting of the Environmental-Mutagen-Society (EMS)
CY SEP 08-12, 2012
CL Bellevue, WA
SP Environm Mutagen Soc (EMS)
C1 [Martin, W. J., II] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0893-6692
J9 ENVIRON MOL MUTAGEN
JI Environ. Mol. Mutagen.
PD SEP
PY 2012
VL 53
SU 1
BP S14
EP S14
PG 1
WC Environmental Sciences; Genetics & Heredity; Toxicology
SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology
GA 993YM
UT WOS:000307896300006
ER
PT J
AU Morita, T
Uno, Y
Kojima, H
Hayashi, M
Tice, R
Corvi, R
Schectman, L
AF Morita, T.
Uno, Y.
Kojima, H.
Hayashi, M.
Tice, R.
Corvi, R.
Schectman, L.
TI The JaCVAM Validation Study of the In Vivo Comet Assay: Selection of
Test Chemicals
SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS
LA English
DT Meeting Abstract
CT 43rd Annual Meeting of the Environmental-Mutagen-Society (EMS)
CY SEP 08-12, 2012
CL Bellevue, WA
SP Environm Mutagen Soc (EMS)
C1 [Morita, T.; Kojima, H.] Natl Inst Hlth Sci, Tokyo, Japan.
[Uno, Y.] Mitsubishi Tanabe Pharma, Chiba, Japan.
[Kojima, H.] Japanese Ctr Validat Alternat Methods, Tokyo, Japan.
[Hayashi, M.] Biosafety Res Ctr, Shizuoka, Japan.
[Tice, R.] NIEHS, Div Natl Toxicol Program, Hillsborough, NC USA.
[Corvi, R.] European Union Reference Lab Alternat Methods Ani, Ispra, Italy.
[Schectman, L.] Innovat Toxicol Consulting LLC, Lake Worth, FL USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0893-6692
J9 ENVIRON MOL MUTAGEN
JI Environ. Mol. Mutagen.
PD SEP
PY 2012
VL 53
SU 1
BP S50
EP S50
PG 1
WC Environmental Sciences; Genetics & Heredity; Toxicology
SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology
GA 993YM
UT WOS:000307896300152
ER
PT J
AU Olanbiwonnu, T
Brooks, P
Tamblyn, L
Laposa, R
AF Olanbiwonnu, T.
Brooks, P.
Tamblyn, L.
Laposa, R.
TI Transcriptional Mutagenesis from 8-oxoguanine or 8,5 '-cyclo-2
'-deoxyadenosine in Adult Neural Stem Cells
SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS
LA English
DT Meeting Abstract
CT 43rd Annual Meeting of the Environmental-Mutagen-Society (EMS)
CY SEP 08-12, 2012
CL Bellevue, WA
SP Environm Mutagen Soc (EMS)
C1 [Olanbiwonnu, T.; Tamblyn, L.; Laposa, R.] Univ Toronto, Toronto, ON, Canada.
[Brooks, P.] NIAAA, Lab Neurogenet, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0893-6692
J9 ENVIRON MOL MUTAGEN
JI Environ. Mol. Mutagen.
PD SEP
PY 2012
VL 53
SU 1
BP S64
EP S64
PG 1
WC Environmental Sciences; Genetics & Heredity; Toxicology
SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology
GA 993YM
UT WOS:000307896300209
ER
PT J
AU Olivero, O
AF Olivero, O.
TI Chromosomal Instability and Aneuploidy Induced by Nucleoside Analogs
SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS
LA English
DT Meeting Abstract
CT 43rd Annual Meeting of the Environmental-Mutagen-Society (EMS)
CY SEP 08-12, 2012
CL Bellevue, WA
SP Environm Mutagen Soc (EMS)
C1 [Olivero, O.] NCI, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0893-6692
J9 ENVIRON MOL MUTAGEN
JI Environ. Mol. Mutagen.
PD SEP
PY 2012
VL 53
SU 1
BP S33
EP S33
PG 1
WC Environmental Sciences; Genetics & Heredity; Toxicology
SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology
GA 993YM
UT WOS:000307896300082
ER
PT J
AU Schaaper, RM
Ahluwalia, D
Bienstock, RJ
AF Schaaper, R. M.
Ahluwalia, D.
Bienstock, R. J.
TI Mutational Consequences of Altered DNA Precursor Pools
SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS
LA English
DT Meeting Abstract
CT 43rd Annual Meeting of the Environmental-Mutagen-Society (EMS)
CY SEP 08-12, 2012
CL Bellevue, WA
SP Environm Mutagen Soc (EMS)
C1 [Schaaper, R. M.; Ahluwalia, D.; Bienstock, R. J.] NIEHS, Res Triangle Pk, NC 27709 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0893-6692
J9 ENVIRON MOL MUTAGEN
JI Environ. Mol. Mutagen.
PD SEP
PY 2012
VL 53
SU 1
BP S31
EP S31
PG 1
WC Environmental Sciences; Genetics & Heredity; Toxicology
SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology
GA 993YM
UT WOS:000307896300077
ER
PT J
AU Swartz, CD
Hobbs, CA
Lentz, C
Garibaldi, P
Green, A
Recio, L
Witt, KL
AF Swartz, C. D.
Hobbs, C. A.
Lentz, C.
Garibaldi, P.
Green, A.
Recio, L.
Witt, K. L.
TI 2-Nitroethanol, but Not Related Nitroalcohols, Is Weakly Mutagenic in
Bacteria and Negative for Chromosomal and DNA Damage
SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS
LA English
DT Meeting Abstract
CT 43rd Annual Meeting of the Environmental-Mutagen-Society (EMS)
CY SEP 08-12, 2012
CL Bellevue, WA
SP Environm Mutagen Soc (EMS)
C1 [Swartz, C. D.; Hobbs, C. A.; Lentz, C.; Garibaldi, P.; Green, A.; Recio, L.] Integrated Syst Lab, Res Triangle Pk, NC USA.
[Witt, K. L.] NIEHS, Res Triangle Pk, NC 27709 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0893-6692
J9 ENVIRON MOL MUTAGEN
JI Environ. Mol. Mutagen.
PD SEP
PY 2012
VL 53
SU 1
BP S57
EP S57
PG 1
WC Environmental Sciences; Genetics & Heredity; Toxicology
SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology
GA 993YM
UT WOS:000307896300178
ER
PT J
AU Simonsen, L
Viboud, C
AF Simonsen, Lone
Viboud, Cecile
TI The Art of Modeling the Mortality Impact of Winter-Seasonal Pathogens
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Editorial Material
ID RESPIRATORY SYNCYTIAL VIRUS; UNITED-STATES; INFLUENZA; HOSPITALIZATIONS;
BURDEN; INFECTIONS; ENGLAND; DEATHS; WALES
C1 [Simonsen, Lone] George Washington Univ, Dept Global Hlth, Washington, DC 20037 USA.
[Simonsen, Lone; Viboud, Cecile] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
RP Simonsen, L (reprint author), George Washington Univ, Dept Publ Hlth, 2175 K St, Washington, DC 20037 USA.
EM lone@gwu.edu
OI Simonsen, Lone/0000-0003-1535-8526
NR 22
TC 5
Z9 5
U1 0
U2 5
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0022-1899
J9 J INFECT DIS
JI J. Infect. Dis.
PD SEP 1
PY 2012
VL 206
IS 5
BP 625
EP 627
DI 10.1093/infdis/jis419
PG 3
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 988PA
UT WOS:000307501800001
PM 22723644
ER
PT J
AU Allison, RD
Conry-Cantilena, C
Koziol, D
Schechterly, C
Ness, P
Gibble, J
Kleiner, DE
Ghany, MG
Alter, HJ
AF Allison, Robert D.
Conry-Cantilena, Cathy
Koziol, Deloris
Schechterly, Cathy
Ness, Paul
Gibble, Joan
Kleiner, David E.
Ghany, Marc G.
Alter, Harvey J.
TI A 25-Year Study of the Clinical and Histologic Outcomes of Hepatitis C
Virus Infection and Its Modes of Transmission in a Cohort of Initially
Asymptomatic Blood Donors
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
ID NON-A; NON-B; TRANSFUSION; ROUTES
AB Background. A total of 738 volunteer blood donors who were positive for anti-hepatitis C virus (HCV) were assessed for risk factors and outcomes for up to 15 years within the study and up to 54 years from the estimated onset of infection.
Methods.A third-generation recombinant immunoblot assay (RIBA) was performed to distinguish true from false anti-HCV reactivity. Findings of HCV polymerase chain reaction classified subjects as having chronic HCV infection or as having recovered. Liver biopsy specimens were staged by Ishak fibrosis score and graded by histologic activity index.
Results.Of 738 anti-HCV-positive subjects, 469 (64%) had positive RIBA results, 217 (29%) had negative results, and 52 (7%) had indeterminate results. Primary independent risk factors were injection drug use (odds ratio [OR], 35.0; P < .0001), blood transfusion (OR, 9.9; P < .0001), and intranasal cocaine use, including 79 "snorters" who repeatedly denied injection drug use or blood transfusion (OR, 8.5; P < .0001). Classification and regression tree and random forest analyses confirmed these risk factors. A total of 384 RIBA-positive donors (82%) were HCV RNA positive; of these, liver biopsy specimens from 185 (48%) showed no fibrosis in 33%, mild fibrosis in 52%, bridging fibrosis in 12%, and cirrhosis in 2% a mean duration of 25 years after infection. Analysis of 63 repeat biopsy specimens showed that 8% progressed >= 2 Ishak stages over 5 years (mean progression, 0.06 Ishak stages/year).
Conclusions.Injection drug use and blood transfusion before 1990 are dominant risk factors for HCV acquisition; intranasal cocaine use may be a surreptitious route of parenteral spread. After a mean of 25 years of HCV infection, histologic outcomes were relatively mild: 85% had no or mild fibrosis, and only 2% had cirrhosis. Nearly one-fifth spontaneously recovered.
C1 [Allison, Robert D.; Conry-Cantilena, Cathy; Schechterly, Cathy; Alter, Harvey J.] NCI, Dept Transfus Med, Bethesda, MD 20892 USA.
[Koziol, Deloris] NCI, Biostat & Clin Epidemiol Serv, Ctr Clin, Bethesda, MD 20892 USA.
[Kleiner, David E.] NCI, Pathol Lab, Bethesda, MD 20892 USA.
[Ghany, Marc G.] NIDDKD, Liver Dis Branch, NIH, Bethesda, MD 20892 USA.
[Ness, Paul] Johns Hopkins Med Inst, Dept Pathol, Baltimore, MD 21205 USA.
[Ness, Paul] Johns Hopkins Med Inst, Dept Oncol, Baltimore, MD 21205 USA.
[Gibble, Joan] Amer Red Cross, Greater Chesapeake & Potomac Reg, Baltimore, MD USA.
RP Alter, HJ (reprint author), NIH, Clin Studies Sect, 10 Ctr Dr,Bldg 10,Rm 1C711, Bethesda, MD 20892 USA.
EM halter@cc.nih.gov
OI Allison, Robert/0000-0001-8458-5250; Kleiner, David/0000-0003-3442-4453
FU Clinical Center, National Institute of Diabetes and Digestive and Kidney
Diseases; National Cancer Institute, National Institutes of Health
FX This work was supported by the Intramural Research Program of the
Clinical Center, National Institute of Diabetes and Digestive and Kidney
Diseases and the National Cancer Institute, National Institutes of
Health.
NR 22
TC 12
Z9 15
U1 0
U2 5
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0022-1899
J9 J INFECT DIS
JI J. Infect. Dis.
PD SEP 1
PY 2012
VL 206
IS 5
BP 654
EP 661
DI 10.1093/infdis/jis410
PG 8
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 988PA
UT WOS:000307501800005
PM 22740714
ER
PT J
AU Blazkova, J
Chun, TW
Belay, BW
Murray, D
Justement, JS
Funk, EK
Nelson, A
Hallahan, CW
Moir, S
Wender, PA
Fauci, AS
AF Blazkova, Jana
Chun, Tae-Wook
Belay, Bietel W.
Murray, Danielle
Justement, J. Shawn
Funk, Emily K.
Nelson, Amy
Hallahan, Claire W.
Moir, Susan
Wender, Paul A.
Fauci, Anthony S.
TI Effect of Histone Deacetylase Inhibitors on HIV Production in Latently
Infected, Resting CD4(+) T Cells From Infected Individuals Receiving
Effective Antiretroviral Therapy
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
ID VALPROIC ACID; RESERVOIR; PROSTRATIN; EXPRESSION; AIDS
AB Persistence of the latent viral reservoir has been recognized as a major obstacle to eradicating human immunodeficiency virus (HIV) in infected individuals receiving antiretroviral therapy. It has been suggested that histone deacetylase inhibitors (HDACis) may purge HIV in the latent viral reservoir. However, the effect of HDACis on the degree and extent of HIV expression in the latent viral reservoir has not been fully delineated. Here we demonstrate that HDACis do not induce HIV production in the latent viral reservoir of aviremic individuals. Therefore, alternative therapeutic strategies may be necessary to eliminate HIV in the latent viral reservoir.
C1 [Chun, Tae-Wook] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA.
[Wender, Paul A.] Stanford Univ, Dept Chem, Stanford, CA 94305 USA.
RP Chun, TW (reprint author), NIAID, Immunoregulat Lab, NIH, Bldg 10,Rm 6A32,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM twchun@nih.gov
FU 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 15
TC 52
Z9 53
U1 3
U2 8
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0022-1899
J9 J INFECT DIS
JI J. Infect. Dis.
PD SEP 1
PY 2012
VL 206
IS 5
BP 765
EP 769
DI 10.1093/infdis/jis412
PG 5
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 988PA
UT WOS:000307501800018
PM 22732922
ER
PT J
AU Caterino, M
Chandler, RJ
Venditti, CP
Ruoppolo, M
AF Caterino, M.
Chandler, R. J.
Venditti, C. P.
Ruoppolo, M.
TI IDENTIFICATION OF DEREGULATED PROTEINS IN METHYLMALONIC ACIDEMIA (MMA)
SO JOURNAL OF INHERITED METABOLIC DISEASE
LA English
DT Meeting Abstract
C1 [Caterino, M.] Fdn SDN, Naples, Italy.
[Chandler, R. J.; Venditti, C. P.] NHGRI, NIH, Bethesda, MD 20892 USA.
[Ruoppolo, M.] Univ Naples Federico II, DBBM, Naples, Italy.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0141-8955
J9 J INHERIT METAB DIS
JI J. Inherit. Metab. Dis.
PD SEP
PY 2012
VL 35
SU 1
BP S60
EP S60
PG 1
WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research &
Experimental
SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental
Medicine
GA 988TH
UT WOS:000307513100202
ER
PT J
AU Huppke, P
Brendel, C
Kalscheuer, V
Korenke, GC
Freisinger, P
Pitelet, G
Wilson, C
Moller, LB
Kaler, SG
Gartner, J
AF Huppke, P.
Brendel, C.
Kalscheuer, V
Korenke, G. C.
Freisinger, P.
Pitelet, G.
Wilson, C.
Moller, L. B.
Kaler, S. G.
Gaertner, J.
TI MUTATIONS IN SLC33A1 CAUSE AN AUTOSOMAL RECESSIVE LETHAL DISORDER WITH
CONGENITAL CATARACTS, BILATERAL HEARING LOSS, DEVELOPMENTAL DELAY AND
REDUCED COPPER AND CERULOPLASMIN IN SERUM
SO JOURNAL OF INHERITED METABOLIC DISEASE
LA English
DT Meeting Abstract
C1 [Huppke, P.; Brendel, C.] Univ Med Gottingen, Gottingen, Germany.
[Kalscheuer, V] Max Planck Inst Mol Genet, D-14195 Berlin, Germany.
[Korenke, G. C.] Childrens Hosp, Dep Neuroped, Oldenburg, Germany.
[Freisinger, P.] Klinikum Steinenberg, Reutlingen, Germany.
[Pitelet, G.] CHU Nice, Serv Neuropediat, Nice, France.
[Wilson, C.] Starship Childrens Hosp, Auckland, New Zealand.
[Moller, L. B.] Kennedy Ctr, Glostrup, Denmark.
[Kaler, S. G.; Gaertner, J.] NIH, Bethesda, MD 20892 USA.
RI Freisinger, Peter/F-2325-2015
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0141-8955
J9 J INHERIT METAB DIS
JI J. Inherit. Metab. Dis.
PD SEP
PY 2012
VL 35
SU 1
BP S17
EP S17
PG 1
WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research &
Experimental
SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental
Medicine
GA 988TH
UT WOS:000307513100052
ER
PT J
AU Pandraud, A
Clayton, P
Foley, AR
Muntoni, F
Johnson, JO
Singleton, AB
Reilly, MM
Houlden, H
AF Pandraud, A.
Clayton, P.
Foley, A. R.
Muntoni, F.
Johnson, J. O.
Singleton, A. B.
Reilly, M. M.
Houlden, H.
TI INVESTIGATION OF RIBOFLAVIN TRANSPORTER MUTATIONS IN BROWN-VIALETTO-VAN
LAERE SYNDROME, A POTENTIALLY TREATABLE METABOLIC DISEASE
SO JOURNAL OF INHERITED METABOLIC DISEASE
LA English
DT Meeting Abstract
C1 [Pandraud, A.; Reilly, M. M.; Houlden, H.] UCL, MRC Ctr Neuromusc Dis, NHNN, ION, London, England.
[Clayton, P.] UCL, Dpt Clin Molec Genet, ICH, London, England.
[Foley, A. R.; Muntoni, F.] UCL, Dubowitz Neuromusc Ctr, ICH, GOSH, London, England.
[Johnson, J. O.; Singleton, A. B.] NIA, Lab Neurogen, NIH, Bethesda, MD 20892 USA.
RI Reilly, Mary/C-8482-2013; Houlden, Henry/C-1532-2008; Singleton,
Andrew/C-3010-2009
OI Houlden, Henry/0000-0002-2866-7777;
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0141-8955
J9 J INHERIT METAB DIS
JI J. Inherit. Metab. Dis.
PD SEP
PY 2012
VL 35
SU 1
BP S18
EP S18
PG 1
WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research &
Experimental
SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental
Medicine
GA 988TH
UT WOS:000307513100053
ER
PT J
AU Schreiber, J
Theodore, WH
Pearl, PL
Gibson, KM
AF Schreiber, J.
Theodore, W. H.
Pearl, P. L.
Gibson, K. M.
TI PHYSIOLOGICAL MARKERS OF TAURINE THERAPY IN SUCCINIC SEMIALDEHYDE
DEHYDROGENASE (SSADH) DEFICIENCY
SO JOURNAL OF INHERITED METABOLIC DISEASE
LA English
DT Meeting Abstract
C1 [Schreiber, J.; Theodore, W. H.] NINDS, Clin Epilepsy Sect, NIH, Bethesda, MD 20892 USA.
[Pearl, P. L.] Childrens Natl Med Ctr, Washington, DC 20010 USA.
[Gibson, K. M.] Wash State Univ, Spokane, WA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0141-8955
J9 J INHERIT METAB DIS
JI J. Inherit. Metab. Dis.
PD SEP
PY 2012
VL 35
SU 1
BP S140
EP S140
PG 1
WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research &
Experimental
SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental
Medicine
GA 988TH
UT WOS:000307513100489
ER
PT J
AU DeKlotz, CC
Cardin, E
Maglione, J
Ried, T
DeWitt, CA
AF DeKlotz, C. C.
Cardin, E.
Maglione, J.
Ried, T.
DeWitt, C. A.
TI All-Trans-Retinoic Acid and Cetuximab: Effects on Colon Adenocarcinoma
Cell Viability
SO JOURNAL OF INVESTIGATIVE DERMATOLOGY
LA English
DT Meeting Abstract
CT 42nd Annual Meeting of the European-Society-for-Dermatological-Research
(ESDR)
CY SEP 07-10, 2012
CL Venice, ITALY
SP European Soc Dermatol Res (ESDR)
C1 [DeKlotz, C. C.; DeWitt, C. A.] Georgetown Univ Hosp, Washington Hosp Ctr, Washington, DC 20007 USA.
[Cardin, E.; Ried, T.] NCI, NIH, Bethesda, MD 20892 USA.
[Maglione, J.] Georgetown Univ, Sch Med, Washington, DC USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0022-202X
J9 J INVEST DERMATOL
JI J. Invest. Dermatol.
PD SEP
PY 2012
VL 132
SU 2
MA 239
BP S42
EP S42
PG 1
WC Dermatology
SC Dermatology
GA 992XM
UT WOS:000307814000239
ER
PT J
AU Elentner, A
Schmuth, M
Hermann, M
Gonzalez, F
Dubrac, S
AF Elentner, A.
Schmuth, M.
Hermann, M.
Gonzalez, F.
Dubrac, S.
TI Pregnane X Receptor (PXR) modulates CCR7 and Langerhans cell migration
via TGF-beta1
SO JOURNAL OF INVESTIGATIVE DERMATOLOGY
LA English
DT Meeting Abstract
CT 42nd Annual Meeting of the European-Society-for-Dermatological-Research
(ESDR)
CY SEP 07-10, 2012
CL Venice, ITALY
SP European Soc Dermatol Res (ESDR)
C1 [Elentner, A.; Schmuth, M.; Dubrac, S.] Innsbruck Med Univ, Dept Dermatol, Innsbruck, Austria.
[Hermann, M.] Dept Gen & Transplant Surg, KTM ZIT Lab, Innsbruck, Austria.
[Gonzalez, F.] NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0022-202X
J9 J INVEST DERMATOL
JI J. Invest. Dermatol.
PD SEP
PY 2012
VL 132
SU 2
MA 010
BP S2
EP S2
PG 1
WC Dermatology
SC Dermatology
GA 992XM
UT WOS:000307814000011
ER
PT J
AU Mascia, F
Keith, C
Lam, G
Yuspa, SH
AF Mascia, F.
Keith, C.
Lam, G.
Yuspa, S. H.
TI Epidermal ablation of EGFR impairs skin immuno-homeostasis and
epithelial differentiation: implication in the pathogenesis of the rash
in patients treated with anti EGFR drugs
SO JOURNAL OF INVESTIGATIVE DERMATOLOGY
LA English
DT Meeting Abstract
CT 42nd Annual Meeting of the European-Society-for-Dermatological-Research
(ESDR)
CY SEP 07-10, 2012
CL Venice, ITALY
SP European Soc Dermatol Res (ESDR)
C1 [Mascia, F.; Keith, C.; Lam, G.; Yuspa, S. H.] NCI, Lab Canc Biol & Genet, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0022-202X
J9 J INVEST DERMATOL
JI J. Invest. Dermatol.
PD SEP
PY 2012
VL 132
SU 2
MA 279
BP S50
EP S50
PG 1
WC Dermatology
SC Dermatology
GA 992XM
UT WOS:000307814000279
ER
PT J
AU Motegi, S
Uchiyama, A
Yamada, K
Ogino, S
Takeuchi, Y
Udey, MC
Ishikawa, O
AF Motegi, S.
Uchiyama, A.
Yamada, K.
Ogino, S.
Takeuchi, Y.
Udey, M. C.
Ishikawa, O.
TI MFG-E8 promotes wound healing in murine skin
SO JOURNAL OF INVESTIGATIVE DERMATOLOGY
LA English
DT Meeting Abstract
CT 42nd Annual Meeting of the European-Society-for-Dermatological-Research
(ESDR)
CY SEP 07-10, 2012
CL Venice, ITALY
SP European Soc Dermatol Res (ESDR)
C1 [Motegi, S.; Uchiyama, A.; Yamada, K.; Ogino, S.; Takeuchi, Y.; Ishikawa, O.] Gunma Univ, Dept Dermatol, Grad Sch Med, Maebashi, Gumma 371, Japan.
[Udey, M. C.] NCI, Dermatol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 1
U2 2
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0022-202X
J9 J INVEST DERMATOL
JI J. Invest. Dermatol.
PD SEP
PY 2012
VL 132
SU 2
MA 040
BP S8
EP S8
PG 1
WC Dermatology
SC Dermatology
GA 992XM
UT WOS:000307814000041
ER
PT J
AU Nagao, K
Kobayashi, T
Kabashima, K
Ohyama, M
Clausen, BE
Udey, MC
Amagai, M
AF Nagao, K.
Kobayashi, T.
Kabashima, K.
Ohyama, M.
Clausen, B. E.
Udey, M. C.
Amagai, M.
TI Stress-induced chemokine production by hair follicles recruit Langerhans
cell precursors to skin
SO JOURNAL OF INVESTIGATIVE DERMATOLOGY
LA English
DT Meeting Abstract
CT 42nd Annual Meeting of the European-Society-for-Dermatological-Research
(ESDR)
CY SEP 07-10, 2012
CL Venice, ITALY
SP European Soc Dermatol Res (ESDR)
C1 [Nagao, K.; Kobayashi, T.; Ohyama, M.; Amagai, M.] Keio Univ, Sch Med, Tokyo, Japan.
[Kabashima, K.] Kyoto Univ, Kyoto, Japan.
[Clausen, B. E.] Erasmus Univ, Med Ctr, Rotterdam, Netherlands.
[Udey, M. C.] NIH, Bethesda, MD 20892 USA.
RI Kabashima, Kenji/G-2521-2014; Nagao, Keisuke/J-5116-2013
OI Kabashima, Kenji/0000-0002-0773-0554; Nagao, Keisuke/0000-0002-7005-3138
NR 0
TC 1
Z9 1
U1 0
U2 2
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0022-202X
J9 J INVEST DERMATOL
JI J. Invest. Dermatol.
PD SEP
PY 2012
VL 132
SU 2
MA 639
BP S112
EP S112
PG 1
WC Dermatology
SC Dermatology
GA 992XM
UT WOS:000307814000636
ER
PT J
AU Nakamura, Y
Franchi, L
Kambe, N
Meng, G
Strober, W
Nunez, G
AF Nakamura, Y.
Franchi, L.
Kambe, N.
Meng, G.
Strober, W.
Nunez, G.
TI Critical Role for Mast Cells in IL-1 beta-Driven Skin Inflammation
Accompanying a Disease-Associated Nlrp3 Mutation
SO JOURNAL OF INVESTIGATIVE DERMATOLOGY
LA English
DT Meeting Abstract
CT 42nd Annual Meeting of the European-Society-for-Dermatological-Research
(ESDR)
CY SEP 07-10, 2012
CL Venice, ITALY
SP European Soc Dermatol Res (ESDR)
C1 [Nakamura, Y.; Franchi, L.; Nunez, G.] Univ Michigan, Sch Med, Dept Pathol, Ann Arbor, MI USA.
[Nakamura, Y.; Franchi, L.; Nunez, G.] Univ Michigan, Sch Med, Ctr Comprehens Canc, Ann Arbor, MI USA.
[Kambe, N.] Chiba Univ, Grad Sch Med, Dept Dermatol, Chiba, Japan.
[Meng, G.] Shanghai Inst Biol Sci, Inst Pasteur Shanghai, Key Lab Mol Virol & Immunol, Unit Innate Immun, Shanghai, Peoples R China.
[Strober, W.] NIAID, Mucosal Immun Sect, Host Def Lab, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 4
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0022-202X
J9 J INVEST DERMATOL
JI J. Invest. Dermatol.
PD SEP
PY 2012
VL 132
SU 2
MA 632
BP S111
EP S111
PG 1
WC Dermatology
SC Dermatology
GA 992XM
UT WOS:000307814000629
ER
PT J
AU Wu, C
Udey, MC
AF Wu, C.
Udey, M. C.
TI Regulation of Tight Junction Composition and Function by the
Claudin-associating Protein EpCAM (CD326)
SO JOURNAL OF INVESTIGATIVE DERMATOLOGY
LA English
DT Meeting Abstract
CT 42nd Annual Meeting of the European-Society-for-Dermatological-Research
(ESDR)
CY SEP 07-10, 2012
CL Venice, ITALY
SP European Soc Dermatol Res (ESDR)
C1 [Wu, C.; Udey, M. C.] NCI, Dermatol Branch, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0022-202X
J9 J INVEST DERMATOL
JI J. Invest. Dermatol.
PD SEP
PY 2012
VL 132
SU 2
MA 252
BP S45
EP S45
PG 1
WC Dermatology
SC Dermatology
GA 992XM
UT WOS:000307814000252
ER
PT J
AU Zhang, XZ
Daucher, M
Baeza, J
Kim, CW
Russell, R
Kottilil, S
AF Zhang, Xiaozhen
Daucher, Marybeth
Baeza, Josue
Kim, Cheol-Woo
Russell, Rodney
Kottilil, Shyamasundaran
TI Human immunodeficiency virus enhances hepatitis C virus replication by
differential regulation of IFN and TGF family genes
SO JOURNAL OF MEDICAL VIROLOGY
LA English
DT Article
DE CD4; HIV; HCV; co-infection; pathogenesis
ID HCV/HIV COINFECTION; CELL-CULTURE; CYTOKINE EXPRESSION; INDUCED
APOPTOSIS; INFECTION; LIVER; HIV-1; BETA; HEPATOCYTES; TIME
AB HIV co-infection significantly impacts the natural history of hepatitis C virus (HCV) by increasing plasma HCV viral load, accelerating liver disease progression, and reducing rates of HCV clearance. Cytokines play an important role in regulating hepatic inflammation and fibrogenesis during chronic HCV infection, yet the impact of HIV on cytokine expression is unknown. In this study, an HCV continuous infection cell culture system was modified to permit co-infection with HIV to test the hypothesis that virus-induced disregulation of immune-response genes, particularly interferons and TGF-beta, may create a permissive environment for the initial establishment of HIV/HCV co-infection in the host. CCR5-expressing Huh-7.5 hepatoma cells were transduced with human CD4 antigen to allow HIV infection in vitro. Co-infection of CD4+ Huh-7.5 cells with HIV and HCV or co-culture of HIV-infected CD4+ Huh-7.5 cells and HCV-infected Huh-7.5 cells increased the level of HCV RNA compared to HCV mono-infection. Quantitative gene expression analysis revealed HIV-induced up regulation of most tested IFN family genes when compared to HCV or co-infection. HCV infection induced up regulation of many TGF family genes that were subsequently down-regulated in the presence of HIV or HIV/HCV. Interestingly, co-infection resulted in down regulation of several IFN genes and significant up regulation of TGF-beta genes leading to an overall enhancement of HCV replication. These data suggest that HIV infection may influence HCV replication in vitro by increasing levels of HCV RNA, possibly through the differential regulation of endogenous IFN and TGF family genes. J. Med. Virol. 84:1344-1352, 2012. (c) 2012 Wiley Periodicals, Inc.
C1 [Zhang, Xiaozhen; Daucher, Marybeth; Baeza, Josue; Kim, Cheol-Woo; Kottilil, Shyamasundaran] NIAID, Immunoregulat Lab, Immunopathogenesis Sect, NIH, Bethesda, MD 20892 USA.
[Russell, Rodney] Mem Univ Newfoundland, Fac Med, Hlth Sci Ctr, St John, NF, Canada.
RP Kottilil, S (reprint author), Magnuson Clin Ctr, Bldg 10,Room 11N204,10 Ctr Dr, Bethesda, MD 20892 USA.
EM skottilil@niaid.nih.gov
FU NIH; National Institute of Allergy and Infectious Diseases
FX Grant sponsor: NIH; Grant sponsor: National Institute of Allergy and
Infectious Diseases.
NR 42
TC 6
Z9 6
U1 1
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0146-6615
J9 J MED VIROL
JI J. Med. Virol.
PD SEP
PY 2012
VL 84
IS 9
BP 1344
EP 1352
DI 10.1002/jmv.23315
PG 9
WC Virology
SC Virology
GA 977IA
UT WOS:000306648800004
PM 22825812
ER
PT J
AU Stojilkovic, SS
Kretschmannova, K
Tomic, M
Stratakis, CA
AF Stojilkovic, S. S.
Kretschmannova, K.
Tomic, M.
Stratakis, C. A.
TI Dependence of the Excitability of Pituitary Cells on Cyclic Nucleotides
SO JOURNAL OF NEUROENDOCRINOLOGY
LA English
DT Review
DE cAMP; cGMP; protein kinase A; protein kinase G; voltage-gated channels
ID CYCLASE-ACTIVATING POLYPEPTIDE; RAT ANTERIOR-PITUITARY;
CORTICOTROPIN-RELEASING HORMONE; PROTEIN-KINASE-A; INTRACELLULAR CA2+
CONCENTRATION; SECRETING ADENOMA CELLS; GATED SODIUM-CHANNELS;
RECTIFYING K+ CURRENT; RECTIFIER POTASSIUM CURRENT; SOLUBLE
ADENYLYL-CYCLASE
AB Cyclic 3',5'-adenosine monophosphate and cyclic 3',5'-guanosine monophosphate are intracellular (second) messengers that are produced from the nucleotide triphosphates by a family of enzymes consisting of adenylyl and guanylyl cyclases. These enzymes are involved in a broad array of signal transduction pathways mediated by the cyclic nucleotide monophosphates and their kinases, which control multiple aspects of cell function through the phosphorylation of protein substrates. We review the findings and working hypotheses on the role of the cyclic nucleotides and their kinases in the control of electrical activity of the endocrine pituitary cells and the plasma membrane channels involved in this process.
C1 Eunice Kennedy Shiver Natl Inst Child Hlth & Huma, Sect Cellular Signalling, NIH, Bethesda, MD USA.
Eunice Kennedy Shiver Natl Inst Child Hlth & Huma, Sect Endocrinol & Genet, NIH, Bethesda, MD USA.
RP Stojilkovic, SS (reprint author), NICHD, Bldg 49,Room 6A-36,49 Convent Dr, Bethesda, MD 20892 USA.
EM stankos@helix.nih.gov
RI Tomic, Melanija/C-3371-2016
FU National Institute of Health, Eunice Kennedy Shriver National Institute
of Child Health and Human Development
FX The authors are thankful to all past and present members of their
laboratories who have contributed to the understanding of the role of
cyclic nucleotides and pituitary cells. This work is supported by the
National Institute of Health, Eunice Kennedy Shriver National Institute
of Child Health and Human Development intramural grants.
NR 207
TC 1
Z9 1
U1 0
U2 7
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0953-8194
J9 J NEUROENDOCRINOL
JI J. Neuroendocrinol.
PD SEP
PY 2012
VL 24
IS 9
BP 1183
EP 1200
DI 10.1111/j.1365-2826.2012.02335.x
PG 18
WC Endocrinology & Metabolism; Neurosciences
SC Endocrinology & Metabolism; Neurosciences & Neurology
GA 989FE
UT WOS:000307544900001
PM 22564128
ER
PT J
AU Abramzon, Y
Johnson, JO
Scholz, SW
Taylor, JP
Brunetti, M
Calvo, A
Mandrioli, J
Benatar, M
Mora, G
Restagno, G
Chio, A
Traynor, BJ
AF Abramzon, Yevgeniya
Johnson, Janel O.
Scholz, Sonja W.
Taylor, J. P.
Brunetti, Maura
Calvo, Andrea
Mandrioli, Jessica
Benatar, Michael
Mora, Gabriele
Restagno, Gabriella
Chio, Adriano
Traynor, Bryan J.
TI Valosin-containing protein (VCP) mutations in sporadic amyotrophic
lateral sclerosis
SO NEUROBIOLOGY OF AGING
LA English
DT Article
DE Amyotrophic lateral sclerosis; Valosin-containing protein; Mutations;
Sporadic disease
ID INCLUSION-BODY MYOPATHY; FRONTOTEMPORAL DEMENTIA; PAGET-DISEASE; ALS;
BONE; FUS; POPULATION; TDP-43
AB We recently reported that mutations in the valosin-containing protein (VCP) gene are a cause of 1%-2% of familial amyotrophic lateral sclerosis (ALS) cases, but their role in the pathogenesis of sporadic ALS is unclear. We undertook mutational screening of VCP in 701 sporadic ALS cases. Three pathogenic variants (p.Arg159Cys, p.Asn387Thr, and p.R662C) were found in three U. S. cases, each of whom presented with progressive upper and lower motor neuron signs consistent with definite ALS by El Escorial diagnostic criteria. Our data indicate that VCP mutations may underlie apparently sporadic ALS but account for <1% of this form of disease. (C) 2012 Elsevier Inc. All rights reserved.
C1 [Abramzon, Yevgeniya; Johnson, Janel O.; Traynor, Bryan J.] NIA, Neuromuscular Dis Res Unit, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
[Scholz, Sonja W.] NIA, Mol Genet Unit, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
[Scholz, Sonja W.] Georgetown Univ, Dept Neurosci, Washington, DC USA.
[Taylor, J. P.] St Jude Childrens Res Hosp, Dept Dev Neurobiol, Memphis, TN 38105 USA.
[Brunetti, Maura; Restagno, Gabriella] ASO OIRM S, Dept Clin Pathol, Mol Genet Unit, Turin, Italy.
[Calvo, Andrea; Chio, Adriano] Univ Turin, Dept Neurosci, Turin, Italy.
[Mandrioli, Jessica] S Agostino Estense Hosp, Dept Neurosci, Modena, Italy.
[Mandrioli, Jessica] Univ Modena, I-41100 Modena, Italy.
[Benatar, Michael] Univ Miami, Dept Neurol, Miami, FL USA.
[Mora, Gabriele] ALS Ctr, Salvatore Maugeri Fdn, Milan, Italy.
[Traynor, Bryan J.] Johns Hopkins Univ, Dept Neurol, Brain Sci Inst, Baltimore, MD 21218 USA.
RP Traynor, BJ (reprint author), NIA, Neuromuscular Dis Res Unit, Neurogenet Lab, NIH, 35 Convent Dr,Room 1A-1000, Bethesda, MD 20892 USA.
EM traynorb@mail.nih.gov
RI Traynor, Bryan/G-5690-2010; Calvo, Andrea/K-4141-2016; MANDRIOLI,
JESSICA/K-7235-2016;
OI Calvo, Andrea/0000-0002-5122-7243; MANDRIOLI,
JESSICA/0000-0002-9244-9782; Chio, Adriano/0000-0001-9579-5341; Scholz,
Sonja/0000-0002-6623-0429
FU National Institutes of Health, National Institute on Aging
[Z01-AG000949-02]; Packard Center for ALS Research at Hopkins; ALS
Association; Fondazione Vialli e Mauro for ALS Research Onlus;
Federazione Italiana Giuoco Calcio (FICG); Ministero della Salute
(Ricerca Sanitaria Finalizzata)
FX This work was supported in part by the Intramural Research Programs of
the National Institutes of Health, National Institute on Aging
(Z01-AG000949-02). The work was also funded by the Packard Center for
ALS Research at Hopkins, the ALS Association, the Fondazione Vialli e
Mauro for ALS Research Onlus, Federazione Italiana Giuoco Calcio (FICG),
and the Ministero della Salute (Ricerca Sanitaria Finalizzata 2007). DNA
samples for this study were obtained in part from the NINDS Human
Genetics DNA and Cell Line Repository at Coriell (www.coriell.org).
NR 22
TC 1
Z9 1
U1 0
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0197-4580
J9 NEUROBIOL AGING
JI Neurobiol. Aging
PD SEP
PY 2012
VL 33
IS 9
AR 2231.e1
DI 10.1016/j.neurobiolaging.2012.04.005
PG 6
WC Geriatrics & Gerontology; Neurosciences
SC Geriatrics & Gerontology; Neurosciences & Neurology
GA 981TW
UT WOS:000306994600041
PM 22572540
ER
PT J
AU Zanotti-Fregonara, P
Liow, JS
Comtat, C
Zoghbi, SS
Zhang, Y
Pike, VW
Fujita, M
Innis, RB
AF Zanotti-Fregonara, Paolo
Liow, Jeih-San
Comtat, Claude
Zoghbi, Sami S.
Zhang, Yi
Pike, Victor W.
Fujita, Masahiro
Innis, Robert B.
TI Image-derived input function in PET brain studies: blood-based methods
are resistant to motion artifacts
SO NUCLEAR MEDICINE COMMUNICATIONS
LA English
DT Article
DE image-derived input function; neuroreceptor tracers; PET
ID POSITRON-EMISSION-TOMOGRAPHY; QUANTIFICATION; PHOSPHODIESTERASE-4;
RECONSTRUCTION; RADIOLIGAND
AB Background Image-derived input function (IDIF) from carotid arteries is an elegant alternative to full arterial blood sampling for brain PET studies. However, a recent study using blood-free IDIFs found that this method is particularly vulnerable to patient motion. The present study used both simulated and clinical [C-11](R)-rolipram data to assess the robustness of a blood-based IDIF method (a method that is ultimately normalized with blood samples) with regard to motion artifacts.
Methods The impact of motion on the accuracy of IDIF was first assessed with an analytical simulation of a high-resolution research tomograph using a numerical phantom of the human brain, equipped with internal carotids. Different degrees of translational (from 1 to 20 mm) and rotational (from 1 to 15 degrees) motions were tested. The impact of motion was then tested on the high-resolution research tomograph dynamic scans of three healthy volunteers, reconstructed with and without an online motion correction system. IDIFs and Logan-distribution volume (V-T) values derived from simulated and clinical scans with motion were compared with those obtained from the scans with motion correction.
Results In the phantom scans, the difference in the area under the curve (AUC) for the carotid time-activity curves was up to 19% for rotations and up to 66% for translations compared with the motionless simulation. However, for the final IDIFs, which were fitted to blood samples, the AUC difference was 11% for rotations and 8% for translations. Logan-V-T errors were always less than 10%, except for the maximum translation of 20 mm, in which the error was 18%. Errors in the clinical scans without motion correction appeared to be minor, with differences in AUC and Logan-V-T always less than 10% compared with scans with motion correction.
Conclusion When a blood-based IDIF method is used for neurological PET studies, the motion of the patient affects IDIF estimation and kinetic modeling only minimally. Nucl Med Commun 33:982-989 (C) 2012 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.
C1 [Zanotti-Fregonara, Paolo; Liow, Jeih-San; Zoghbi, Sami S.; Zhang, Yi; Pike, Victor W.; Fujita, Masahiro; Innis, Robert B.] NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA.
[Comtat, Claude] CEA SHFJ, Orsay, France.
RP Innis, RB (reprint author), NIMH, Mol Imaging Branch, NIH, Bldg 10,Room B1 D43,Ctr Dr,MSC 1026, Bethesda, MD 20892 USA.
EM innisr@mail.nih.gov
FU Intramural Research Program of the National Institute of Mental Health,
National Institutes of Health (IRP-NIMH-NIH)
FX The authors gratefully acknowledge the support of the Intramural
Research Program of the National Institute of Mental Health, National
Institutes of Health (IRP-NIMH-NIH). The authors thank Thada Shantalaxmi
for help with the HRRT scan reconstructions. Ioline Henter provided
invaluable editorial assistance.
NR 23
TC 3
Z9 3
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0143-3636
J9 NUCL MED COMMUN
JI Nucl. Med. Commun.
PD SEP
PY 2012
VL 33
IS 9
BP 982
EP 989
DI 10.1097/MNM.0b013e328356185c
PG 8
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 988ZX
UT WOS:000307531100012
PM 22760300
ER
PT J
AU Kessler, RC
Avenevoli, S
McLaughlin, KA
Green, JG
Lakoma, MD
Petukhova, M
Pine, DS
Sampson, NA
Zaslavsky, AM
Merikangas, KR
AF Kessler, R. C.
Avenevoli, S.
McLaughlin, K. A.
Green, J. Greif
Lakoma, M. D.
Petukhova, M.
Pine, D. S.
Sampson, N. A.
Zaslavsky, A. M.
Merikangas, K. Ries
TI Lifetime co-morbidity of DSM-IV disorders in the US National Comorbidity
Survey Replication Adolescent Supplement (NCS-A)
SO PSYCHOLOGICAL MEDICINE
LA English
DT Article
DE Adolescence; epidemiology; lifetime co-morbidity; lifetime prevalence;
mental disorders; NCS-A
ID COMMON MENTAL-DISORDERS; EARLY DEVELOPMENTAL-STAGES;
SOCIAL-ANXIETY-DISORDER; AGE-OF-ONSET; DEPRESSIVE-DISORDERS; SUBSTANCE
USE; PSYCHIATRIC-DISORDERS; HEALTH SURVEYS; YOUNG-ADULTS; BIRTH COHORT
AB Background. Research on the structure of co-morbidity among common mental disorders has largely focused on current prevalence rather than on the development of co-morbidity. This report presents preliminary results of the latter type of analysis based on the US National Comorbidity Survey Replication Adolescent Supplement (NCS-A).
Method. A national survey was carried out of adolescent mental disorders. DSM-IV diagnoses were based on the Composite International Diagnostic Interview (CIDI) administered to adolescents and questionnaires self-administered to parents. Factor analysis examined co-morbidity among 15 lifetime DSM-IV disorders. Discrete-time survival analysis was used to predict first onset of each disorder from information about prior history of the other 14 disorders.
Results. Factor analysis found four factors representing fear, distress, behavior and substance disorders. Associations of temporally primary disorders with the subsequent onset of other disorders, dated using retrospective age-of-onset (AOO) reports, were almost entirely positive. Within-class associations (e. g. distress disorders predicting subsequent onset of other distress disorders) were more consistently significant (63.2%) than between-class associations (33.0%). Strength of associations decreased as co-morbidity among disorders increased. The percentage of lifetime disorders explained (in a predictive rather than a causal sense) by temporally prior disorders was in the range 3.7-6.9% for earliest-onset disorders [specific phobia and attention deficit hyperactivity disorder (ADHD)] and much higher (23.1-64.3%) for later-onset disorders. Fear disorders were the strongest predictors of most other subsequent disorders.
Conclusions. Adolescent mental disorders are highly co-morbid. The strong associations of temporally primary fear disorders with many other later-onset disorders suggest that fear disorders might be promising targets for early interventions.
C1 [Kessler, R. C.; Petukhova, M.; Sampson, N. A.; Zaslavsky, A. M.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA.
[Avenevoli, S.] NIMH, Div Dev Translat Res, Bethesda, MD 20892 USA.
[McLaughlin, K. A.] Harvard Univ, Sch Med, Childrens Hosp Boston, Div Gen Pediat, Boston, MA 02115 USA.
[Green, J. Greif] Boston Univ, Sch Educ, Boston, MA 02215 USA.
[Lakoma, M. D.] Harvard Univ, Sch Med, Dept Populat Med, Boston, MA 02115 USA.
[Pine, D. S.] NIMH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA.
[Merikangas, K. Ries] NIMH, Div Intramural Res Programs, Bethesda, MD 20892 USA.
RP Kessler, RC (reprint author), Harvard Univ, Sch Med, Dept Hlth Care Policy, 180 Longwood Ave, Boston, MA 02115 USA.
EM ncs@hcp.med.harvard.edu
OI McLaughlin, Katie/0000-0002-1362-2410
FU National Institute of Mental Health (NIMH) [U01-MH60220, R01-MH66627,
U01MH060220-09S1, R01-MH070884, R13-MH066849, R01-MH069864,
R01-MH077883]; National Institute on Drug Abuse (NIDA) [R01-DA016558];
Substance Abuse and Mental Health Services Administration (SAMHSA);
Robert Wood Johnson Foundation (RWJF) [044780]; John W. Alden Trust;
NIMH Intramural Research Program; NIMH [R01-MH66627]; Fogarty
International Center of the National Institutes of Health [FIRCA
R03-TW006481]; John D. and Catherine T. MacArthur Foundation; Pfizer
Foundation; Pan American Health Organization; AstraZeneca; Bristol-Myers
Squibb; Eli Lilly Company; GlaxoSmithKline; Ortho-McNeil; Pfizer;
Sanofi-Aventis; Wyeth; Analysis Group Inc.; EPI-Q; Johnson & Johnson
Pharmaceuticals; Ortho-McNeil Janssen Scientific Affairs; Pfizer Inc.;
Sanofi-Aventis Groupe; Shire US, Inc.
FX The NCS-A is supported by the National Institute of Mental Health (NIMH;
U01-MH60220, R01-MH66627 and U01MH060220-09S1) with supplemental support
from the National Institute on Drug Abuse (NIDA), the Substance Abuse
and Mental Health Services Administration (SAMHSA), the Robert Wood
Johnson Foundation (RWJF; Grant 044780), and the John W. Alden Trust.
The work of Dr Merikangas is supported by the NIMH Intramural Research
Program. The work of Dr Zaslavsky is supported by NIMH Grant
R01-MH66627. A complete list of NCS-A publications can be found at
www.hcp.med.harvard.edu/ncs. A public use version of the NCS-A dataset
is available for secondary analysis. Instructions for accessing the
dataset can be found at www.hcp.med.harvard.edu/ncs/index.php. The NCS-A
is carried out in conjunction with the World Health Organization World
Mental Health (WMH) Survey Initiative. We thank the staff of the WMH
Data Collection and Data Analysis Coordination Centres for assistance
with instrumentation, fieldwork and consultation on data analysis. The
WMH Data Coordination Centres have received support from NIMH
(R01-MH070884, R13-MH066849, R01-MH069864, R01-MH077883), NIDA
(R01-DA016558), the Fogarty International Center of the National
Institutes of Health (FIRCA R03-TW006481), the John D. and Catherine T.
MacArthur Foundation, the Pfizer Foundation, and the Pan American Health
Organization. The WMH Data Coordination Centres have also received
unrestricted educational grants from AstraZeneca, Bristol-Myers Squibb,
Eli Lilly & Company, GlaxoSmithKline, Ortho-McNeil, Pfizer,
Sanofi-Aventis, and Wyeth. A complete list of WMH publications can be
found at www.hcp.med.harvard.edu/wmh/. The views and opinions expressed
in this report are those of the authors and should not be construed to
represent the views of any of the sponsoring organizations, agencies, or
the US Government. All authors had full access to the survey data. Dr
Kessler takes responsibility for the integrity of the data and the
accuracy of the data analysis.; R. C. Kessler has been a consultant for
AstraZeneca, Analysis Group, Bristol-Myers Squibb, Cerner-Galt
Associates, Eli Lilly & Company, GlaxoSmithKline Inc., HealthCore Inc.,
Health Dialog, Integrated Benefits Institute, John Snow Inc., Kaiser
Permanente, Matria Inc., Mensante, Merck & Co., Inc., Ortho-McNeil
Janssen Scientific Affairs, Pfizer Inc., Primary Care Network, Research
Triangle Institute, Sanofi-Aventis Groupe, Shire US Inc., SRA
International, Inc., Takeda Global Research & Development, Transcept
Pharmaceuticals Inc., and Wyeth-Ayerst; has served on advisory boards
for Appliance Computing II, Eli Lilly & Company, Mindsite, Ortho-McNeil
Janssen Scientific Affairs, and Wyeth-Ayerst; and has had research
support for his epidemiological studies from Analysis Group Inc.,
Bristol-Myers Squibb, Eli Lilly & Company, EPI-Q, GlaxoSmithKline,
Johnson & Johnson Pharmaceuticals, Ortho-McNeil Janssen Scientific
Affairs., Pfizer Inc., Sanofi-Aventis Groupe, and Shire US, Inc.
NR 58
TC 71
Z9 72
U1 4
U2 48
PU CAMBRIDGE UNIV PRESS
PI NEW YORK
PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA
SN 0033-2917
J9 PSYCHOL MED
JI Psychol. Med.
PD SEP
PY 2012
VL 42
IS 9
BP 1997
EP 2010
DI 10.1017/S0033291712000025
PG 14
WC Psychology, Clinical; Psychiatry; Psychology
SC Psychology; Psychiatry
GA 984LE
UT WOS:000307190400021
PM 22273480
ER
PT J
AU Jiang, CC
Zhao, ML
Waters, KM
Diaz, M
AF Jiang, Chuancang
Zhao, Ming-Lang
Waters, Katherine M.
Diaz, Marilyn
TI Activation-induced deaminase contributes to the antibody-independent
role of B cells in the development of autoimmunity
SO AUTOIMMUNITY
LA English
DT Article
DE Somatic hypermutation; AID; B cells; T cells; lupus
ID SOMATIC MUTATION; IMMUNE-RESPONSE; STRANDED-DNA; SYSTEMIC AUTOIMMUNITY;
GERMINAL-CENTERS; LUPUS NEPHRITIS; DEFICIENT MICE; MRL/LPR MICE;
AUTOANTIBODIES; HYPERMUTATION
AB B cells contribute to autoimmunity both as secretors of pathogenic antibodies and through the activation of autoreactive T cells. B cells and antibodies acquire higher affinity to self-antigen through a process known as immunoglobulin hypermutation or SHM. The contribution of SHM to pathogenic antibody development in lupus has been established in various autoimmune mouse models and by examining antibodies from patients. However, its role in the antibody-independent contribution of B cells to autoimmunity has not been examined. Herein, we generate lupus-prone MRL/lpr mice with a limited IgM-only B cell repertoire, no secreted antibodies and no SHM. This enabled us to isolate the role of somatic hypermutation in B cell-mediated autoimmunity. We found that SHM-deficiency correlated with a reduction in autoreactive B cells, a decrease in T cell activation and a decrease in kidney lymphocytic infiltration. These data establish AID as an important contributor to the antibody-independent role of B cells in autoimmunity.
C1 [Jiang, Chuancang; Zhao, Ming-Lang; Waters, Katherine M.; Diaz, Marilyn] NIEHS, Somat Hypermutat Grp, Mol Genet Lab, NIH, Res Triangle Pk, NC 27709 USA.
RP Diaz, M (reprint author), NIEHS, Somat Hypermutat Grp, Mol Genet Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.
EM diaz@niehs.nih.gov
FU NIH, National Institute of Environmental Health Sciences [Z01 ES101603]
FX The authors declare no conflict of interest. This research was supported
by the Intramural Research Program of the NIH, National Institute of
Environmental Health Sciences. Project Z01 ES101603.
NR 38
TC 6
Z9 6
U1 0
U2 3
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 0891-6934
J9 AUTOIMMUNITY
JI Autoimmunity
PD SEP
PY 2012
VL 45
IS 6
BP 440
EP 448
DI 10.3109/08916934.2012.682668
PG 9
WC Immunology
SC Immunology
GA 985VT
UT WOS:000307299300002
PM 22559231
ER
PT J
AU Igarashi, M
Kim, HW
Gao, F
Chang, L
Ma, KZ
Rapoport, SI
AF Igarashi, Miki
Kim, Hyung-Wook
Gao, Fei
Chang, Lisa
Ma, Kaizong
Rapoport, Stanley I.
TI Fifteen weeks of dietary n-3 polyunsaturated fatty acid deprivation
increase turnover of n-6 docosapentaenoic acid in rat-brain
phospholipids
SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS
LA English
DT Article
DE Docosapentaenoic; Docosahexaenoic; Turnover; Brain; Diet; PUFA
ID ALPHA-LINOLENIC ACID; THIN-LAYER CHROMATOGRAPHY; AIN-93 PURIFIED DIETS;
DOCOSAHEXAENOIC ACID; ARACHIDONIC-ACID; PUFA DEPRIVATION; NUTRITIONAL
DEPRIVATION; ADULT-RATS; LIVER CONVERSION; BIPOLAR DISORDER
AB Docosapentaenoic acid (DPAn-6, 22:5n-6) is an n-6 polyunsaturated fatty acid (PUFA) whose brain concentration can be increased in rodents by dietary n-3 PUPA deficiency, which may contribute to their behavioral dysfunction. We used our in vivo intravenous infusion method to see if brain DPAn-6 turnover and metabolism also were altered with deprivation. We studied male rats that had been fed for 15 weeks post-weaning an n-3 PUFA adequate diet containing 4.6% alpha-linolenic acid (alpha-LNA, 18:3n-3) or a deficient diet (0.2% alpha-LNA), each lacking docosahexaenoic acid (22:6n-3) and arachidonic acid (AA, 20:4n-6). [1-C-14]DPAn-6 was infused intravenously for 5 min in unanesthetized rats, after which the brain underwent high-energy micro-waving, and then was analyzed. The n-3 PUFA deficient compared with adequate diet increased DPAn-6 and decreased DHA concentrations in plasma and brain, while minimally changing brain AA concentration. Incorporation rates of unesterified DPAn-6 from plasma into individual brain phospholipids were increased 5.2-7.7 fold, while turnover rates were increased 2.1-4.7 fold. The observations suggest that increased metabolism and brain concentrations of DPAn-6 and its metabolites, together with a reduced brain DHA concentration, contribute to behavioral and functional abnormalities reported with dietary n-3 PUFA deprivation in rodents. (196 words) Published by Elsevier B.V.
C1 [Igarashi, Miki; Kim, Hyung-Wook; Gao, Fei; Chang, Lisa; Ma, Kaizong; Rapoport, Stanley I.] NIA, Brain Physiol & Metab Sect, NIH, Bethesda, MD 20892 USA.
RP Igarashi, M (reprint author), NIA, Brain Physiol & Metab Sect, NIH, Bldg 9,Room 1S126, Bethesda, MD 20892 USA.
EM miki.i@uci.edu
FU National Institute on Aging
FX This research was supported entirely by the Intramural Research Program
of the National Institute on Aging. The authors thank the NIH Fellows'
Editorial Board for editorial assistance.
NR 80
TC 7
Z9 8
U1 0
U2 8
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1388-1981
EI 0006-3002
J9 BBA-MOL CELL BIOL L
JI Biochim. Biophys. Acta Mol. Cell Biol. Lipids
PD SEP
PY 2012
VL 1821
IS 9
BP 1235
EP 1243
DI 10.1016/j.bbalip.2011.11.002
PG 9
WC Biochemistry & Molecular Biology; Biophysics; Cell Biology
SC Biochemistry & Molecular Biology; Biophysics; Cell Biology
GA 984NX
UT WOS:000307198800007
PM 22142872
ER
PT J
AU Cheon, Y
Kim, HW
Igarashi, M
Modi, HR
Chang, L
Ma, KZ
Greenstein, D
Wohltmann, M
Turk, J
Rapoport, SI
Taha, AY
AF Cheon, Yewon
Kim, Hyung-Wook
Igarashi, Miki
Modi, Hiren R.
Chang, Lisa
Ma, Kaizong
Greenstein, Deanna
Wohltmann, Mary
Turk, John
Rapoport, Stanley I.
Taha, Ameer Y.
TI Disturbed brain phospholipid and docosahexaenoic acid metabolism in
calcium-independent phospholipase A(2)-VIA (iPLA(2)beta)-knockout mice
SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS
LA English
DT Article
DE Mouse; DHA; Turnover; Incorporation; Lipid; PLA2G6
ID POLYUNSATURATED FATTY-ACIDS; INFANTILE NEUROAXONAL DYSTROPHY;
CYCLOOXYGENASE-2 KNOCKOUT MOUSE; GROUP-SPECIFIC ASSAYS; N-3 PUFA
DEPRIVATION; ALPHA-LINOLENIC ACID; RAT-BRAIN; ARACHIDONIC-ACID;
NUTRITIONAL DEPRIVATION; DENDRITIC PATHOLOGY
AB Calcium-independent phospholipase A(2) group VIA (iPLA(2)beta) releases docosahexaenoic acid (DNA) from phospholipids in vitro. Mutations in the iPLA(2)beta gene, PLA2G6, are associated with dystonia-parkinsonism and infantile neuroaxonal dystrophy. To understand the role of iPLA(2)beta in brain, we applied our in vivo kinetic method using radiolabeled DHA in 4 to 5-month-old wild type (iPLA(2)beta(+/+)) and knockout (iPLA(2)beta(-/-)) mice, and measured brain DHA kinetics, lipid concentrations, and expression of PLA(2), cyclooxygenase (COX), and lipoxygenase (LOX) enzymes. Compared to iPLA(2)beta(+/+) mice, iPLA(2)beta(-/-) mice showed decreased rates of incorporation of unesterified DHA from plasma into brain phospholipids, reduced concentrations of several fatty acids (including DHA) esterified in ethanolamine- and serine-glycerophospholipids, and increased lysophospholipid fatty acid concentrations. DHA turnover in brain phospholipids did not differ between genotypes. In iPLA(2)beta(-/-) mice, brain levels of iPLA(2)beta mRNA, protein, and activity were decreased, as was the iPLA(2)gamma (Group VIB PLA(2)) mRNA level, while levels of secretory sPLA(2)-V mRNA, protein, and activity and cytosolic cPLA(2)-IVA mRNA were increased. Levels of COX-1 protein were decreased in brain, while COX-2 protein and mRNA were increased. Levels of 5-, 12-, and 15-LOX proteins did not differ significantly between genotypes. Thus, a genetic iPLA(2)beta deficiency in mice is associated with reduced DHA metabolism, profound changes in lipid-metabolizing enzyme expression (demonstrating lack of redundancy) and of phospholipid fatty acid content of brain (particularly of DHA), which may be relevant to neurologic abnormalities in humans with PLA2G6 mutations. Published by Elsevier B.V.
C1 [Cheon, Yewon; Kim, Hyung-Wook; Igarashi, Miki; Modi, Hiren R.; Chang, Lisa; Ma, Kaizong; Rapoport, Stanley I.; Taha, Ameer Y.] NIA, Brain Physiol & Metab Sect, NIH, Bethesda, MD 20892 USA.
[Greenstein, Deanna] NIMH, Child Psychiat Branch, NIH, Bethesda, MD 20892 USA.
[Wohltmann, Mary; Turk, John] Washington Univ, Sch Med, Dept Med, Mass Spectrometry Facil, St Louis, MO 63110 USA.
[Wohltmann, Mary; Turk, John] Washington Univ, Sch Med, Div Endocrinol Metab & Lipid Res, St Louis, MO 63110 USA.
RP Cheon, Y (reprint author), NIA, Brain Physiol & Metab Sect, NIH, 9000 Rockville Pike,Bldg 9,1S126, Bethesda, MD 20892 USA.
EM cheony@mail.nih.gov
FU National Institute on Aging; National Institute of Mental Health,
National Institutes of Health; NIH [R37-DK34388, P41-RR00954,
P60-DK20579, P30-DK56341]
FX The work conducted by Y. Cheon, H-W. Kim, M. Igarashi, H. R. Modi, L.
Chang, K. Ma, S. I. Rapoport and A. Y. Taha was supported by the
Intramural Research Program of the National Institute on Aging and that
by D. Greenstein by the Intramural Research Program of the National
Institute of Mental Health, National Institutes of Health. The work
conducted by M. Wohltmann and J. Turk was supported by NIH grants
R37-DK34388, P41-RR00954, P60-DK20579, and P30-DK56341. We appreciate
the editorial assistance of the NIH Fellows Editorial Board.
NR 68
TC 17
Z9 18
U1 0
U2 7
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1388-1981
J9 BBA-MOL CELL BIOL L
JI Biochim. Biophys. Acta Mol. Cell Biol. Lipids
PD SEP
PY 2012
VL 1821
IS 9
BP 1278
EP 1286
DI 10.1016/j.bbalip.2012.02.003
PG 9
WC Biochemistry & Molecular Biology; Biophysics; Cell Biology
SC Biochemistry & Molecular Biology; Biophysics; Cell Biology
GA 984NX
UT WOS:000307198800011
PM 22349267
ER
PT J
AU Agochukwu, NB
Solomon, BD
Muenke, M
AF Agochukwu, Nneamaka B.
Solomon, Benjamin D.
Muenke, Maximilian
TI Impact of genetics on the diagnosis and clinical management of syndromic
craniosynostoses
SO CHILDS NERVOUS SYSTEM
LA English
DT Article
DE Syndromic craniosynostoses; Craniosynostosis syndromes; Management
craniosynostosis; Craniosynostosis; Diagnosis craniosynostosis; FGFR
craniosynostosis
ID SAETHRE-CHOTZEN-SYNDROME; JACKSON-WEISS-SYNDROME; AUTOSOMAL-DOMINANT
CRANIOSYNOSTOSIS; FRONTO-ORBITAL ADVANCEMENT; GROWTH-FACTOR RECEPTOR-2;
FGFR1 P252R MUTATION; APERT-SYNDROME; PFEIFFER-SYNDROME;
CROUZON-SYNDROME; MUENKE-SYNDROME
AB More than 60 different mutations have been identified to be causal in syndromic forms of craniosynostosis. The majority of these mutations occur in the fibroblast growth factor receptor 2 gene (FGFR2). The clinical management of syndromic craniosynostosis varies based on the particular causal mutation. Additionally, the diagnosis of a patient with syndromic craniosynostosis is based on the clinical presentation, signs, and symptoms. The understanding of the hallmark features of particular syndromic forms of craniosynostosis leads to efficient diagnosis, management, and long-term prognosis of patients with syndromic craniosynostoses.
A comprehensive literature review was done with respect to the major forms of syndromic craniosynostosis and additional less common FGFR-related forms of syndromic craniosynostosis. Additionally, information and data gathered from studies performed in our own investigative lab (lab of Dr. Muenke) were further analyzed and reviewed. A literature review was also performed with regard to the genetic workup and diagnosis of patients with craniosynostosis.
Patients with Apert syndrome (craniosynostosis syndrome due to mutations in FGFR2) are most severely affected in terms of intellectual disability, developmental delay, central nervous system anomalies, and limb anomalies. All patients with FGFR-related syndromic craniosynostosis have some degree of hearing loss that requires thorough initial evaluations and subsequent follow-up.
Patients with syndromic craniosynostosis require management and treatment of issues involving multiple organ systems which span beyond craniosynostosis. Thus, effective care of these patients requires a multidisciplinary approach.
C1 [Agochukwu, Nneamaka B.; Muenke, Maximilian] NIH, Clin Res Training Program, Bethesda, MD 20892 USA.
[Agochukwu, Nneamaka B.; Solomon, Benjamin D.; Muenke, Maximilian] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA.
RP Muenke, M (reprint author), NIH, Clin Res Training Program, MSC 3717,Bldg 35,Room 1B-203, Bethesda, MD 20892 USA.
EM mamuenke@mail.nih.gov
FU Intramural NIH HHS [Z99 HG999999]
NR 109
TC 14
Z9 14
U1 1
U2 11
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0256-7040
EI 1433-0350
J9 CHILD NERV SYST
JI Childs Nerv. Syst.
PD SEP
PY 2012
VL 28
IS 9
BP 1447
EP 1463
DI 10.1007/s00381-012-1756-2
PG 17
WC Clinical Neurology; Pediatrics; Surgery
SC Neurosciences & Neurology; Pediatrics; Surgery
GA 987IS
UT WOS:000307411000026
PM 22872262
ER
PT J
AU Nah, HD
Koyama, E
Agochukwu, NB
Bartlett, SP
Muenke, M
AF Nah, Hyun-Duck
Koyama, Eiki
Agochukwu, Nneamaka B.
Bartlett, Scott P.
Muenke, Maximilian
TI Phenotype profile of a genetic mouse model for Muenke syndrome
SO CHILDS NERVOUS SYSTEM
LA English
DT Article
DE Muenke syndrome; Genetic mouse model; FGFR3
ID GROWTH-FACTOR RECEPTOR-3; CORONAL CRANIOSYNOSTOSIS; PRO250ARG MUTATION;
CRANIAL BASE; HEARING-LOSS; INNER-EAR; CELL FATE; FIBROBLAST; FGFR3;
ACHONDROPLASIA
AB The Muenke syndrome mutation (FGFR3 (P250R) ), which was discovered 15 years ago, represents the single most common craniosynostosis mutation. Muenke syndrome is characterized by coronal suture synostosis, midface hypoplasia, subtle limb anomalies, and hearing loss. However, the spectrum of clinical presentation continues to expand. To better understand the pathophysiology of the Muenke syndrome, we present collective findings from several recent studies that have characterized a genetically equivalent mouse model for Muenke syndrome (FgfR3 (P244R) ) and compare them with human phenotypes.
FgfR3 (P244R) mutant mice show premature fusion of facial sutures, premaxillary and/or zygomatic sutures, but rarely the coronal suture. The mice also lack the typical limb phenotype. On the other hand, the mutant mice display maxillary retrusion in association with a shortening of the anterior cranial base and a premature closure of intersphenoidal and spheno-occipital synchondroses, resembling human midface hypoplasia. In addition, sensorineural hearing loss is detected in all FgfR3 (P244R) mutant mice as in the majority of Muenke syndrome patients. It is caused by a defect in the mechanism of cell fate determination in the organ of Corti. The mice also express phenotypes that have not been previously described in humans, such as reduced cortical bone thickness, hypoplastic trabecular bone, and defective temporomandibular joint structure. Therefore, the FgfR3 (P244R) mouse provides an excellent opportunity to study disease mechanisms of some classical phenotypes of Muenke syndrome and to test novel therapeutic strategies. The mouse model can also be further explored to discover previously unreported yet potentially significant phenotypes of Muenke syndrome.
C1 [Nah, Hyun-Duck; Koyama, Eiki] Univ Penn, Childrens Hosp Philadelphia, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Nah, Hyun-Duck; Bartlett, Scott P.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Agochukwu, Nneamaka B.; Muenke, Maximilian] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA.
[Agochukwu, Nneamaka B.] NIH, Clin Res Training Program, Bethesda, MD 20892 USA.
RP Nah, HD (reprint author), Univ Penn, Childrens Hosp Philadelphia, Perelman Sch Med, 1116G ARC,3615 Civ Ctr Blvd, Philadelphia, PA 19104 USA.
EM nah@email.chop.edu
FU NIH/NIAMS; Mary Downs Endowment Chair Fund; Division of Intramural
Research at the National Human Genome Research Institute (National
Institutes of Health, Department of Health and Human Services, United
States of America)
FX We thank Drs. Steven R. Twigg and Andrew O. Wilkie (Oxford University,
Cambridge, UK) for sharing the FgfR3P244R mice with us. The
studies on the basicranial synchondrosis and the temporomandibular joint
were supported by a grant from NIH/NIAMS to H-D.N. and Mary Downs
Endowment Chair Fund to S. P. B. We would like to express our gratitude
to our patients for their willingness to take part in ongoing studies at
the NIH on Muenke syndrome. These studies were supported in part by the
Division of Intramural Research at the National Human Genome Research
Institute (National Institutes of Health, Department of Health and Human
Services, United States of America).
NR 57
TC 5
Z9 5
U1 1
U2 3
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0256-7040
J9 CHILD NERV SYST
JI Childs Nerv. Syst.
PD SEP
PY 2012
VL 28
IS 9
BP 1483
EP 1493
DI 10.1007/s00381-012-1778-9
PG 11
WC Clinical Neurology; Pediatrics; Surgery
SC Neurosciences & Neurology; Pediatrics; Surgery
GA 987IS
UT WOS:000307411000029
PM 22872265
ER
PT J
AU Shen, YN
Cooper, GF
AF Shen, Yanna
Cooper, Gregory F.
TI Multivariate Bayesian modeling of known and unknown causes of events-An
application to biosurveillance
SO COMPUTER METHODS AND PROGRAMS IN BIOMEDICINE
LA English
DT Article
DE Bayesian modeling; Unknown causes of events; Disease outbreak detection
ID OUTBREAKS; ALGORITHM
AB This paper investigates Bayesian modeling of known and unknown causes of events in the context of disease-outbreak detection. We introduce a multivariate Bayesian approach that models multiple evidential features of every person in the population. This approach models and detects (1) known diseases (e.g., influenza and anthrax) by using informative prior probabilities and (2) unknown diseases (e.g., a new, highly contagious respiratory virus that has never been seen before) by using relatively non-informative prior probabilities. We report the results of simulation experiments which support that this modeling method can improve the detection of new disease outbreaks in a population. A contribution of this paper is that it introduces a multivariate Bayesian approach for jointly modeling both known and unknown causes of events. Such modeling has general applicability in domains where the space of known causes is incomplete. (C) 2010 Elsevier Ireland Ltd. All rights reserved.
C1 [Cooper, Gregory F.] Univ Pittsburgh, Dept Biomed Informat, Pittsburgh, PA USA.
[Shen, Yanna] Lister Hill Natl Ctr Biomed Commun, Bethesda, MD USA.
[Shen, Yanna] Univ Pittsburgh, Intelligent Syst Program, Pittsburgh, PA USA.
RP Shen, YN (reprint author), US Natl Lib Med, Lister Hill Natl Ctr Biomed Commun 38A 9N912A, 8600 Rockville Pike, Bethesda, MD 20894 USA.
EM yanna.shen@nih.gov
FU National Science Foundation [IIS-0325581, IIS-0911032]; Centers for
Disease Control and Prevention [P01-HK000086]
FX This research was funded by grants IIS-0325581 and IIS-0911032 from the
National Science Foundation and by grant P01-HK000086 from the Centers
for Disease Control and Prevention.
NR 33
TC 1
Z9 1
U1 0
U2 6
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0169-2607
J9 COMPUT METH PROG BIO
JI Comput. Meth. Programs Biomed.
PD SEP
PY 2012
VL 107
IS 3
BP 436
EP 446
DI 10.1016/j.cmpb.2010.11.015
PG 11
WC Computer Science, Interdisciplinary Applications; Computer Science,
Theory & Methods; Engineering, Biomedical; Medical Informatics
SC Computer Science; Engineering; Medical Informatics
GA 983CI
UT WOS:000307093400008
PM 21195503
ER
PT J
AU He, L
Long, LR
Antani, S
Thoma, GR
AF He, Lei
Long, L. Rodney
Antani, Sameer
Thoma, George R.
TI Histology image analysis for carcinoma detection and grading
SO COMPUTER METHODS AND PROGRAMS IN BIOMEDICINE
LA English
DT Article
DE Histopathology; Carcinoma; Histology image analysis; Image segmentation;
Feature extraction; Computed assisted diagnosis
ID NONLINEAR DIMENSIONALITY REDUCTION; ACTIVE CONTOUR MODELS;
BREAST-CANCER; LUNG-CANCER; FLUORESCENCE MICROSCOPY; THRESHOLDING
TECHNIQUES; ANISOTROPIC DIFFUSION; TEXTURE FEATURES; TISSUE-SECTIONS;
SEGMENTATION
AB This paper presents an overview of the image analysis techniques in the domain of histopathology, specifically, for the objective of automated carcinoma detection and classification. As in other biomedical imaging areas such as radiology, many computer assisted diagnosis (CAD) systems have been implemented to aid histopathologists and clinicians in cancer diagnosis and research, which have been attempted to significantly reduce the labor and subjectivity of traditional manual intervention with histology images. The task of automated histology image analysis is usually not simple due to the unique characteristics of histology imaging, including the variability in image preparation techniques, clinical interpretation protocols, and the complex structures and very large size of the images themselves. In this paper we discuss those characteristics, provide relevant background information about slide preparation and interpretation, and review the application of digital image processing techniques to the field of histology image analysis. In particular, emphasis is given to state-of-the-art image segmentation methods for feature extraction and disease classification. Four major carcinomas of cervix, prostate, breast, and lung are selected to illustrate the functions and capabilities of existing CAD systems. Published by Elsevier Ireland Ltd.
C1 [He, Lei; Long, L. Rodney; Antani, Sameer; Thoma, George R.] NIH, Natl Lib Med, Bethesda, MD USA.
RP He, L (reprint author), NIH, Natl Lib Med, 8600 Rockville Pike, Bethesda, MD USA.
EM leihe2005@gmail.com
OI Antani, Sameer/0000-0002-0040-1387
FU Intramural Research Program of the National Institutes of Health (NIH);
National Library of Medicine (NLM); Lister Hill National Center for
Biomedical Communications (LHNCBC)
FX This research was supported by the Intramural Research Program of the
National Institutes of Health (NIH), National Library of Medicine (NLM),
and Lister Hill National Center for Biomedical Communications (LHNCBC).
NR 161
TC 47
Z9 48
U1 1
U2 34
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0169-2607
EI 1872-7565
J9 COMPUT METH PROG BIO
JI Comput. Meth. Programs Biomed.
PD SEP
PY 2012
VL 107
IS 3
BP 538
EP 556
DI 10.1016/j.cmpb.2011.12.007
PG 19
WC Computer Science, Interdisciplinary Applications; Computer Science,
Theory & Methods; Engineering, Biomedical; Medical Informatics
SC Computer Science; Engineering; Medical Informatics
GA 983CI
UT WOS:000307093400017
PM 22436890
ER
PT J
AU Li, H
Spencer, SD
Lian, L
Zhang, Z
Lu, P
AF Li, H.
Spencer, S. D.
Lian, L.
Zhang, Z.
Lu, P.
TI Phylogenetic analysis of the nucleoprotein gene of measles viruses
prevalent in Nantong, Jiangsu Province, China, during 2010
SO EPIDEMIOLOGY AND INFECTION
LA English
DT Article
DE Measles (rubeola)
ID MOLECULAR EPIDEMIOLOGY
AB Measles control in China is monitored in part by surveillance of circulating wild-type viruses. The objective of this study was genetic characterization and phylogenetic analysis of measles strains in the Nantong City region of Jiangsu province, China, during 2010. Sera from suspected cases were tested for IgM antibodies and measles virus isolated by inoculation of transport medium onto Vero/SLAM cells. Isolated strains were phylogenetically analysed according to the nucleotide sequence of the C-terminal region of the nucleoprotein gene amplified by RT-PCR. The results revealed 34 cases confirmed by positive IgM, for an incidence of 0.45/100 000. Six isolates identified were all clustered within genotype H1. The findings reported here support continued endemic transmission of measles virus in China.
C1 [Li, H.] Nantong Ctr Dis Control & Prevent, Dept Microbiol, Nantong 226007, Jiangsu, Peoples R China.
[Spencer, S. D.] NCI, SAIC Frederick Inc, Bethesda, MD 20892 USA.
[Lian, L.; Zhang, Z.] Nantong Ctr Dis Control & Prevent, Dept Immunizat Program, Nantong 226007, Jiangsu, Peoples R China.
[Lu, P.] Jiangsu Ctr Dis Control & Prevent, Dept Immunizat Program, Nanjing, Jiangsu, Peoples R China.
RP Li, H (reprint author), Nantong Ctr Dis Control & Prevent, Dept Microbiol, 99 Hongxing Rd, Nantong 226007, Jiangsu, Peoples R China.
EM ntlihaibo@gmail.com
FU Jiangsu Prevention Medicine Foundation [YZ201014]
FX This study was supported by the financial grants from Jiangsu Prevention
Medicine Foundation (YZ201014).
NR 8
TC 0
Z9 1
U1 0
U2 2
PU CAMBRIDGE UNIV PRESS
PI NEW YORK
PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA
SN 0950-2688
J9 EPIDEMIOL INFECT
JI Epidemiol. Infect.
PD SEP
PY 2012
VL 140
IS 9
BP 1607
EP 1611
DI 10.1017/S0950268811002433
PG 5
WC Public, Environmental & Occupational Health; Infectious Diseases
SC Public, Environmental & Occupational Health; Infectious Diseases
GA 985QR
UT WOS:000307283700009
PM 22117136
ER
PT J
AU Salvadore, G
van der Veen, JW
Zhang, Y
Marenco, S
Machado-Vieira, R
Baumann, J
Ibrahim, LA
Luckenbaugh, DA
Shen, J
Drevets, WC
Zarate, CA
AF Salvadore, Giacomo
van der Veen, Jan Willem
Zhang, Yan
Marenco, Stefano
Machado-Vieira, Rodrigo
Baumann, Jacqueline
Ibrahim, Lobna A.
Luckenbaugh, David A.
Shen, Jun
Drevets, Wayne C.
Zarate, Carlos A., Jr.
TI An investigation of amino-acid neurotransmitters as potential predictors
of clinical improvement to ketamine in depression
SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY
LA English
DT Article
DE biomarkers; glutamate; glutamine; magnetic resonance spectroscopy (MRS);
major depressive disorder (MDD)
ID MAGNETIC-RESONANCE-SPECTROSCOPY; D-ASPARTATE ANTAGONIST; RAPID
ANTIDEPRESSANT RESPONSE; RESISTANT MAJOR DEPRESSION; ANTERIOR CINGULATE;
GLUTAMATERGIC SYSTEM; GABA CONCENTRATIONS; PREFRONTAL CORTEX; OCCIPITAL
CORTEX; MOOD DISORDERS
AB Amino-acid neurotransmitter system dysfunction plays a major role in the pathophysiology of major depressive disorder (MDD). We used proton magnetic resonance spectroscopy (H-1-MRS) to investigate whether prefrontal levels of amino-acid neurotransmitters predict antidepressant response to a single intravenous infusion of the N-methyl-D-aspartate (NMDA) antagonist ketamine in MDD patients. Fourteen drug-free patients with MDD were scanned 1-3 d before receiving a single intravenous infusion of ketamine (0.5 mg/kg). We measured gamma aminobutyric acid (GABA), glutamate, and Glx/glutamate ratio (a surrogate marker of glutamine) in the ventromedial prefrontal cortex (VM-PFC) and the dorsomedial/dorsal anterolateral prefrontal cortex (DM/DA-PFC). Correlation analyses were conducted to determine whether pretreatment GABA, glutamate, or Glx/glutamate ratio predicted change in depressive and anxiety symptoms 230 min after ketamine administration. Pretreatment GABA or glutamate did not correlate with improved depressive symptoms in either of the two regions of interest (p > 0.1); pretreatment Glx/glutamate ratio in the DM/DA-PFC was negatively correlated with improvement in depressive symptoms [r(s)(11) = -0.57, p < 0.05]. Pretreatment glutamate levels in the VM-PFC were positively correlated with improvement in anxiety symptoms [r(s)(11) = 0.57, p < 0.05]. The findings suggest an association between lower Glx/glutamate ratio and greater improvement in response to ketamine treatment. Because glutamine is mainly contained in glia, the decreased Glx/glutamate ratio observed in this study may reflect the reduction in glial cells found in the same regions in post-mortem studies of individuals with MDD, and suggests that the presence of this neuropathological construct may be associated with antidepressant responsiveness to ketamine.
C1 [Salvadore, Giacomo; Machado-Vieira, Rodrigo; Baumann, Jacqueline; Ibrahim, Lobna A.; Luckenbaugh, David A.; Zarate, Carlos A., Jr.] NIMH, Dept Hlth & Human Serv, Expt Therapeut & Pathophysiol Branch, Div Intramural Res Program,NIH, Bethesda, MD 20892 USA.
[van der Veen, Jan Willem; Zhang, Yan; Shen, Jun] NIMH, Magnet Resonance Spect Core, NIH, Bethesda, MD 20892 USA.
[Marenco, Stefano] NIMH, Gene Cognit & Psychosis Program, NIH, Bethesda, MD 20892 USA.
[Drevets, Wayne C.] NIMH, Sect Neuroimaging Mood & Anxiety Disorders, NIH, Bethesda, MD 20892 USA.
[Drevets, Wayne C.] Univ Oklahoma, Coll Med, Laureate Inst Brain Res, Dept Psychiat, Tulsa, OK USA.
[Machado-Vieira, Rodrigo] Inst & Dept Sao Paulo, LIM27, Sao Paulo, Brazil.
RP Salvadore, G (reprint author), Johnson & Johnson PRD, 1125 Trenton Harbourton Rd, Titusville, NJ 08560 USA.
EM gsalvado@its.jnj.com
RI Marenco, Stefano/A-2409-2008; MACHADO-VIEIRA, RODRIGO/D-8293-2012
OI Marenco, Stefano/0000-0002-2488-2365; MACHADO-VIEIRA,
RODRIGO/0000-0002-4830-1190
FU Intramural Research Program of the National Institute of Mental Health,
National Institutes of Health (IRP-NIMH-NIH)
FX This research was supported by the Intramural Research Program of the
National Institute of Mental Health, National Institutes of Health
(IRP-NIMH-NIH). Ioline Henter (NIMH) provided invaluable editorial
assistance.
NR 44
TC 27
Z9 27
U1 2
U2 20
PU CAMBRIDGE UNIV PRESS
PI NEW YORK
PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA
SN 1461-1457
EI 1469-5111
J9 INT J NEUROPSYCHOPH
JI Int. J. Neuropsychopharmacol.
PD SEP
PY 2012
VL 15
IS 8
BP 1063
EP 1072
DI 10.1017/S1461145711001593
PG 10
WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA 984KH
UT WOS:000307188000005
PM 22040773
ER
PT J
AU Malkesman, O
Austin, DR
Tragon, T
Wang, G
Rompala, G
Hamidi, AB
Cui, ZZ
Young, WS
Nakazawa, K
Zarate, CA
Manji, HK
Chen, G
AF Malkesman, Oz
Austin, Daniel R.
Tragon, Tyson
Wang, Gang
Rompala, Gregory
Hamidi, Anahita B.
Cui, Zhenzhong
Young, W. Scott
Nakazawa, Kazu
Zarate, Carlos A., Jr.
Manji, Husseini K.
Chen, Guang
TI Acute D-serine treatment produces antidepressant-like effects in rodents
SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY
LA English
DT Article
DE Antidepressant; D-serine; glutamate; N-methyl-D-aspartate receptor
(NMDAR); NR1 knockout
ID MAJOR DEPRESSIVE DISORDER; D-ASPARTATE ANTAGONIST; STAR-ASTERISK-D;
MOOD-DISORDERS; MESSENGER-RNA; ANIMAL-MODELS; RAT-BRAIN; SYNAPTIC
PLASTICITY; PREFRONTAL CORTEX; BIPOLAR DISORDER
AB Research suggests that dysfunctional glutamatergic signalling may contribute to depression, a debilitating mood disorder affecting millions of individuals worldwide. Ketamine, a N-methyl-D-aspartate (NMDA) receptor antagonist, exerts rapid antidepressant effects in approximately 70% of patients. Glutamate evokes the release of D-serine from astrocytes and neurons, which then acts as a co-agonist and binds at the glycine site on the NR1 subunit of NMDA receptors. Several studies have implicated glial deficits as one of the underlying facets of the neurobiology of depression. The present study tested the hypothesis that D-serine modulates behaviours related to depression. The behavioural effects of a single, acute D-serine administration were examined in several rodent tests of antidepressant-like effects, including the forced swim test (FST), the female urine sniffing test (FUST) following serotonin depletion, and the learned helplessness (LH) paradigm. D-serine significantly reduced immobility in the FST without affecting general motor function. Both D-serine and ketamine significantly rescued sexual reward-seeking deficits caused by serotonin depletion in the FUST. Finally, D-serine reversed LH behaviour, as measured by escape latency, number of escapes, and percentage of mice developing LH. Mice lacking NR1 expression in forebrain excitatory neurons exhibited a depression-like phenotype in the same behavioural tests, and did not respond to D-serine treatment. These findings suggest that D-serine produces antidepressant-like effects and support the notion of complex glutamatergic dysfunction in depression. It is unclear whether D-serine has a convergent influence on downstream synaptic plasticity cascades that may yield a similar therapeutic profile to NMDA antagonists like ketamine.
C1 [Malkesman, Oz; Austin, Daniel R.; Tragon, Tyson; Wang, Gang; Rompala, Gregory; Hamidi, Anahita B.; Manji, Husseini K.; Chen, Guang] NIMH, Mol Pathophysiol Lab, NIH, Bethesda, MD 20892 USA.
[Cui, Zhenzhong; Young, W. Scott] NIMH, Sect Neural Gene Express, NIH, Bethesda, MD 20892 USA.
[Nakazawa, Kazu] NIMH, Unit Genet Cognit & Behav, NIH, Bethesda, MD 20892 USA.
[Zarate, Carlos A., Jr.] NIMH, Expt Therapeut & Pathophysiol Branch, Intramural Res Program, NIH, Bethesda, MD 20892 USA.
[Manji, Husseini K.; Chen, Guang] Johnson & Johnson Pharmaceut Res & Dev, Titusville, NJ USA.
RP Chen, G (reprint author), J&J Pharmaceut Res & Dev LLC, 3210 Merryfield Row, San Diego, CA 92121 USA.
EM GChen13@its.jnj.com
RI Young, W Scott/A-9333-2009; Nakazawa, Kazutoshi/J-6195-2015; Chen,
Guang/A-2570-2017
OI Young, W Scott/0000-0001-6614-5112; Nakazawa,
Kazutoshi/0000-0001-5699-9093;
FU Intramural Research Program of the National Institute of Mental Health,
National Institutes of Health (IRP-NIMH-NIH)
FX All authors gratefully acknowledge the support of the Intramural
Research Program of the National Institute of Mental Health, National
Institutes of Health (IRP-NIMH-NIH). H. K. M. and G. C. are currently
full-time employees of Johnson and Johnson Pharmaceutical Research and
Development (USA); all of this work was initiated and most was conducted
while they were employees of the NIMH. A patent application for the use
of ketamine in depression has been submitted listing Dr Manji and Dr
Zarate among the inventors; they have assigned their rights on the
patent to the U.S. Government.
NR 73
TC 27
Z9 28
U1 0
U2 15
PU CAMBRIDGE UNIV PRESS
PI NEW YORK
PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA
SN 1461-1457
J9 INT J NEUROPSYCHOPH
JI Int. J. Neuropsychopharmacol.
PD SEP
PY 2012
VL 15
IS 8
BP 1135
EP 1148
DI 10.1017/S1461145711001386
PG 14
WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA 984KH
UT WOS:000307188000011
PM 21906419
ER
PT J
AU Wadiwala, MF
Kamal, AK
AF Wadiwala, Muhammad Faisal
Kamal, Ayeesha Kamran
TI What is better antiplatelet agent to prevent recurrent stroke?
SO JOURNAL OF THE PAKISTAN MEDICAL ASSOCIATION
LA English
DT Editorial Material
C1 [Kamal, Ayeesha Kamran] Aga Khan Univ Hosp, Stroke Serv, Karachi, Pakistan.
Aga Khan Univ Hosp, Vasc Fellowship Program, Int Cerebrovasc Translat Clin Res Training Progra, Fogarty Int Ctr, Karachi, Pakistan.
Aga Khan Univ Hosp, Vasc Fellowship Program, Int Cerebrovasc Translat Clin Res Training Progra, Natl Inst Neurol Disorders & Stroke, Karachi, Pakistan.
RP Kamal, AK (reprint author), Aga Khan Univ Hosp, Stroke Serv, Karachi, Pakistan.
EM ayeesha.kamal@aku.edu
FU FIC NIH HHS [D43TW008660, D43 TW008660]
NR 1
TC 0
Z9 0
U1 0
U2 0
PU PAKISTAN MEDICAL ASSOC
PI KARACHI
PA PMA HOUSE, AGA KHAN III RD, KARACHI, 00000, PAKISTAN
SN 0030-9982
J9 J PAK MED ASSOC
JI J. Pak. Med. Assoc.
PD SEP
PY 2012
VL 62
IS 9
BP 976
EP 977
PG 2
WC Medicine, General & Internal; Medicine, Research & Experimental
SC General & Internal Medicine; Research & Experimental Medicine
GA 983UJ
UT WOS:000307143900028
PM 23139991
ER
PT J
AU Kron, MA
Wang, C
Vodanovic-Jankovic, S
Howard, OMZ
Kuhn, LA
AF Kron, Michael A.
Wang, Cheng
Vodanovic-Jankovic, Sanja
Howard, O. M. Zack
Kuhn, Leslie A.
TI Interleukin-8-like activity in a filarial asparaginyl-tRNA synthetase
SO MOLECULAR AND BIOCHEMICAL PARASITOLOGY
LA English
DT Article
DE Aminoacyl-tRNA synthetase; Chemokine; Interleukin-8 (IL-8); Filaria;
Immunoregulation; Receptors
ID N-TERMINAL DOMAIN; BRUGIA-MALAYI; CHEMOKINE RECEPTORS; PROTEIN; CXCR1
AB A wide range of secondary biological functions have been documented for eukaryotic aminoacyl-tRNA synthetases including roles in transcriptional regulation, mitochondrial RNA splicing, cell growth, and chemokine-like activities. The asparaginyl-tRNA synthetase (AsnRS) of the filarial nematode, Brugia malayi, is a highly expressed excretory-secretory molecule which activates interleukin 8 (IL-8) receptors via extracellular domains that are different from those used by IL-8. Recent success in determining the complete atomic structure of the B. malayi AsnRS provided the opportunity to map its chemokine-like activity. Chemotaxis assays demonstrated that IL-8-like activity is localized in a novel 80 amino acid amino terminal substructure. Structural homology searches revealed similarities between that domain in B. malayi AsnRS and substructures involved in receptor binding by human IL-8. These observations provide important new insights into how parasite-derived molecules may play a role in the modulation of immune cell function. (C) 2012 Published by Elsevier B.V.
C1 [Kron, Michael A.; Wang, Cheng; Vodanovic-Jankovic, Sanja] Med Coll Wisconsin, Dept Med, Biotechnol & Bioengn Ctr, Milwaukee, WI 53092 USA.
[Howard, O. M. Zack] NCI, Mol Immunoregulat Lab, Frederick, MD 21701 USA.
[Kuhn, Leslie A.] Michigan State Univ, Dept Biochem & Mol Biol, E Lansing, MI 48824 USA.
[Kuhn, Leslie A.] Michigan State Univ, Dept Comp Sci & Engn, E Lansing, MI 48824 USA.
RP Kron, MA (reprint author), Med Coll Wisconsin, Dept Med, Biotechnol & Bioengn Ctr, C2805 Clin Translat Sci Bldg,8701 Watertown Pk Rd, Milwaukee, WI 53092 USA.
EM mkron@mcw.edu
RI Howard, O M Zack/B-6117-2012
OI Howard, O M Zack/0000-0002-0505-7052
FU U.S. National Institutes of Health [NIAID UO1 A153877]
FX This work was supported in part by a grant from the U.S. National
Institutes of Health (NIAID UO1 A153877) to M.K. and LK. We thank Sai
Chetan Sukuru for his early analysis of the AsnRS catalytic and
anticodon binding domains for IL-8-like sequence and structural motifs.
NR 20
TC 7
Z9 7
U1 0
U2 0
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0166-6851
J9 MOL BIOCHEM PARASIT
JI Mol. Biochem. Parasitol.
PD SEP
PY 2012
VL 185
IS 1
BP 66
EP 69
DI 10.1016/j.molbiopara.2012.06.003
PG 4
WC Biochemistry & Molecular Biology; Parasitology
SC Biochemistry & Molecular Biology; Parasitology
GA 987MH
UT WOS:000307420700009
PM 22710390
ER
PT J
AU Lerman, BJ
Hoffman, EP
Sutherland, ML
Bouri, K
Hsu, DK
Liu, FT
Rothstein, JD
Knoblach, SM
AF Lerman, Bruce J.
Hoffman, Eric P.
Sutherland, Margaret L.
Bouri, Khaled
Hsu, Daniel K.
Liu, Fu-Tong
Rothstein, Jeffrey D.
Knoblach, Susan M.
TI Deletion of galectin-3 exacerbates microglial activation and accelerates
disease progression and demise in a SOD1(G93A) mouse model of
amyotrophic lateral sclerosis
SO BRAIN AND BEHAVIOR
LA English
DT Article
DE Alternative activation; amyotrophic lateral sclerosis; microglia; motor
neuron disease; SOD1
AB Galectins are pleiotropic carbohydrate-binding lectins involved in inflammation, growth/differentiation, and tissue remodeling. The functional role of galectins in amyotrophic lateral sclerosis (ALS) is unknown. Expression studies revealed increases in galectin-1 mRNA and protein in spinal cords from SOD1(G93A) mice, and in galectin-3 and -9 mRNAs and proteins in spinal cords of both SOD1(G93A) mice and sporadic ALS patients. As the increase in galectin-3 appeared in early presymptomatic stages and increased progressively through to end stage of disease in the mouse, it was selected for additional study, where it was found to be mainly expressed by microglia. Galectin-3 antagonists are not selective and do not readily cross the blood-brain barrier; therefore, we generated SOD1(G93A)/Gal-3(-/-) transgenic mice to evaluate galectin-3 deletion in a widely used mouse model of ALS. Disease progression, neurological symptoms, survival, and inflammation were assessed to determine the effect of galectin-3 deletion on the SOD1(G93A) disease phenotype. Galectin-3 deletion did not change disease onset, but resulted in more rapid progression through functionally defined disease stages, more severely impaired neurological symptoms at all stages of disease, and expiration, on average, 25 days earlier than SOD1(G93A)/Gal-3(+/+) cohorts. In addition, microglial staining, as well as TNF-alpha, and oxidative injury were increased in SOD1(G93A)/Gal-3(-/-) mice compared with SOD1(G93A)/Gal-3(+/+) cohorts. These data support an important functional role for microglial galectin-3 in neuroinflammation during chronic neurodegenerative disease. We suggest that elevations in galectin-3 by microglia as disease progresses may represent a protective, anti-inflammatory innate immune response to chronic motor neuron degeneration.
C1 [Lerman, Bruce J.] George Washington Univ, Sch Med & Hlth Sci, Dept Pharmacol, Washington, DC 20052 USA.
[Hoffman, Eric P.; Knoblach, Susan M.] George Washington Univ, Sch Med & Hlth Sci, Dept Integrat Syst Biol, Washington, DC 20052 USA.
[Hoffman, Eric P.; Bouri, Khaled; Knoblach, Susan M.] Childrens Natl Med Ctr, Dept Pediat, Washington, DC 20010 USA.
[Hoffman, Eric P.; Bouri, Khaled; Knoblach, Susan M.] Childrens Natl Med Ctr, Ctr Genet Med, Washington, DC 20010 USA.
[Sutherland, Margaret L.] NINDS, Neurodegenerat Cluster, NIH, Rockville, MD USA.
[Hsu, Daniel K.; Liu, Fu-Tong] Univ Calif Davis, Sch Med, Dept Dermatol, Sacramento, CA 95817 USA.
[Rothstein, Jeffrey D.] Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21218 USA.
RP Knoblach, SM (reprint author), Childrens Natl Med Ctr, Med Genet Res Ctr, 111 Michigan Ave NE, Washington, DC 20010 USA.
EM sknoblach@cnmcresearch.org
FU NIH/NINDS [NS041679]; NIH NCMRR/NINDS (NCMRR-DC Core Molecular and
Functional Outcome Measures in Rehabilitation Medicine)
[2R24HD050846-06]; NIH NINDS (Intellectual and Developmental
Disabilities Research Center) [5R01NS029525, 1P30HD40677-06]
FX This work was partially supported by NIH/NINDS NS041679, NIH NCMRR/NINDS
2R24HD050846-06 (NCMRR-DC Core Molecular and Functional Outcome Measures
in Rehabilitation Medicine), and by NIH NINDS 5R01NS029525 (Intellectual
and Developmental Disabilities Research Center 1P30HD40677-06).
NR 59
TC 19
Z9 19
U1 0
U2 0
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 2162-3279
J9 BRAIN BEHAV
JI Brain Behav.
PD SEP
PY 2012
VL 2
IS 5
BP 563
EP 575
DI 10.1002/brb3.75
PG 13
WC Behavioral Sciences; Neurosciences
SC Behavioral Sciences; Neurosciences & Neurology
GA V35UT
UT WOS:000209174200005
PM 23139902
ER
PT J
AU Armstrong, AY
Eltoukhi, H
Segars, JH
AF Armstrong, A. Y.
Eltoukhi, H.
Segars, J. H.
TI THE IMPACT OF HEALTH CARE REFORM ON ACCESS TO ART IN THE US
SO FERTILITY AND STERILITY
LA English
DT Meeting Abstract
C1 [Armstrong, A. Y.; Eltoukhi, H.; Segars, J. H.] NICHD, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD 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 0015-0282
EI 1556-5653
J9 FERTIL STERIL
JI Fertil. Steril.
PD SEP
PY 2012
VL 98
IS 3
SU S
MA P-481
BP S254
EP S254
PG 1
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA V45UY
UT WOS:000209842700845
ER
PT J
AU Beall, S
Moon, K
Widra, E
DeCherney, A
Chang, F
Richter, K
AF Beall, S.
Moon, K.
Widra, E.
DeCherney, A.
Chang, F.
Richter, K.
TI CHARACTERISTICS PREDICTIVE OF FAILED LEUPROLIDE ACETATE (LA) TRIGGER
AMONG PATIENTS UNDERGOING GONADOTROPIN-RELEASING HORMONE (GNRH)
ANTAGONIST SUPPRESSION FOR VITRO FERTILIZATION (IVF).
SO FERTILITY AND STERILITY
LA English
DT Meeting Abstract
C1 [Beall, S.; Moon, K.; DeCherney, A.; Richter, K.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD USA.
[Widra, E.; Chang, F.] Shady Grove Fertil Reprod Sci Ctr, Rockville, MD 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 0015-0282
EI 1556-5653
J9 FERTIL STERIL
JI Fertil. Steril.
PD SEP
PY 2012
VL 98
IS 3
SU S
MA P-207
BP S172
EP S172
PG 1
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA V45UY
UT WOS:000209842700575
ER
PT J
AU Beall, S
Moon, K
Widra, E
DeCherney, A
Chang, F
Richter, K
AF Beall, S.
Moon, K.
Widra, E.
DeCherney, A.
Chang, F.
Richter, K.
TI MATCHED SAMPLES COMPARISON OF IN VITRO FERTILIZATION (IVF) CLINICAL
OUTCOMES ASSOCIATED WITH LEUPROLIDE ACETATE ( LA) VERSUS HUMAN CHORIONIC
GONADOTROPIN (hCG) TRIGGER FOR OOCYTE MATURATION
SO FERTILITY AND STERILITY
LA English
DT Meeting Abstract
CT 68th Annual Meeting of the American-Society-for-Reproductive-Medicine
(ASRM)
CY OCT 20-24, 2012
CL San Diego, CA
SP Amer Soc Reprod Med
C1 [Beall, S.; Moon, K.; DeCherney, A.; Richter, K.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD USA.
[Widra, E.; Chang, F.] Shady Grove Fertil Reprod Sci Ctr, Rockville, MD 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 0015-0282
EI 1556-5653
J9 FERTIL STERIL
JI Fertil. Steril.
PD SEP
PY 2012
VL 98
IS 3
SU S
MA O-175
BP S53
EP S53
PG 1
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA V45UY
UT WOS:000209842700174
ER
PT J
AU Beall, S
Betz, G
Segars, J
Chang, F
Richter, K
AF Beall, S.
Betz, G.
Segars, J.
Chang, F.
Richter, K.
TI DRAMATIC PROGRAM-WIDE REDUCTION IN THE INCIDENCE OF SEVERE OVARIAN
HYPERSTIMULATION SYNDROME (OHSS) REQUIRING PARACENTESIS WITH SELECTIVE
USE OF GONADOTROPIN-RELEASING HORMONE (GNRH) AGONIST TRIGGER.
SO FERTILITY AND STERILITY
LA English
DT Meeting Abstract
C1 [Beall, S.; Segars, J.; Chang, F.; Richter, K.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD USA.
[Betz, G.] Shady Grove Fertil Reprod Sci Ctr, Rockville, MD 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 0015-0282
EI 1556-5653
J9 FERTIL STERIL
JI Fertil. Steril.
PD SEP
PY 2012
VL 98
IS 3
SU S
MA P-204
BP S171
EP S171
PG 1
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA V45UY
UT WOS:000209842700572
ER
PT J
AU Beall, S
Moon, K
Widra, E
Segars, J
Chang, F
Richter, K
AF Beall, S.
Moon, K.
Widra, E.
Segars, J.
Chang, F.
Richter, K.
TI HUMAN CHORIONIC GONADOTROPIN (hCG) RE-TRIGGER FOLLOWING A POOR RESPONSE
TO LEUPROLIDE ACETATE (LA) TRIGGER IS NOT ASSOCIATED WITH POOR IN VITRO
FERTILIZATION (IVF) TREATMENT OUTCOMES
SO FERTILITY AND STERILITY
LA English
DT Meeting Abstract
CT 68th Annual Meeting of the American-Society-for-Reproductive-Medicine
(ASRM)
CY OCT 20-24, 2012
CL San Diego, CA
SP Amer Soc Reprod Med
C1 [Beall, S.; Moon, K.; Segars, J.; Richter, K.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD USA.
[Widra, E.; Chang, F.] Shady Grove Fertil Reprod Sci Ctr, Rockville, MD USA.
NR 0
TC 1
Z9 1
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0015-0282
EI 1556-5653
J9 FERTIL STERIL
JI Fertil. Steril.
PD SEP
PY 2012
VL 98
IS 3
SU S
MA O-170
BP S52
EP S52
PG 1
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA V45UY
UT WOS:000209842700169
ER
PT J
AU Bolnick, JM
Kilburn, BA
Bajpayee, S
Reddy, N
Diamond, MP
Armant, DR
AF Bolnick, J. M.
Kilburn, B. A.
Bajpayee, S.
Reddy, N.
Diamond, M. P.
Armant, D. R.
TI ISOLATION OF TROPHOBLAST CELLS FROM TRANSCERVICAL SPECIMENS FOR PRENATAL
DETERMINATION OF FETAL SEX BY SINGLE-CELL ANALYSIS.
SO FERTILITY AND STERILITY
LA English
DT Meeting Abstract
C1 [Bolnick, J. M.; Kilburn, B. A.; Bajpayee, S.; Reddy, N.; Diamond, M. P.; Armant, D. R.] Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI USA.
[Armant, D. R.] NICHD, Program Reprod & Adult Endocrinol, NIH, DHHS, Bethesda, MD 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 0015-0282
EI 1556-5653
J9 FERTIL STERIL
JI Fertil. Steril.
PD SEP
PY 2012
VL 98
IS 3
SU S
MA P-72
BP S133
EP S133
PG 1
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA V45UY
UT WOS:000209842700442
ER
PT J
AU Broomfield, DP
Kulak, D
Plowden, TC
Mumford, S
Armstrong, AY
AF Broomfield, D. P.
Kulak, D.
Plowden, T. C.
Mumford, S.
Armstrong, A. Y.
TI SALPINGECTOMY IS COST EFFECTIVE WHEN THE POST SURGICAL PREGNANCY RATE IS
TWICE THE PREGNANCY RATE OF PATIENTS WITH HYDROSALPINGES: A DECISION
TREE MATHEMATICAL MODEL WITH SENSITIVITY ANALYSIS
SO FERTILITY AND STERILITY
LA English
DT Meeting Abstract
C1 [Broomfield, D. P.] Howard Univ Hosp, Obstet & Gynecol, Washington, DC USA.
[Kulak, D.] Montefiore Med Ctr, Obstet & Gynecol, Bronx, NY 10467 USA.
[Plowden, T. C.] Bayne Jones Army Community Hosp, Obstet & Gynecol, Ft Polk, LA USA.
[Mumford, S.] NICHD, Epidemiol & Populat Stat, NIH, Bethesda, MD USA.
[Armstrong, A. Y.] NICHD, Clin Serv Program Reprod & Adult Endocrinol, NIH, Bethesda, MD 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 0015-0282
EI 1556-5653
J9 FERTIL STERIL
JI Fertil. Steril.
PD SEP
PY 2012
VL 98
IS 3
SU S
MA P-595
BP S288
EP S288
PG 1
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA V45UY
UT WOS:000209842700951
ER
PT J
AU Brzyski, RG
Barnhart, K
Santoro, N
Eisenberg, E
AF Brzyski, R. G.
Barnhart, K.
Santoro, N.
Eisenberg, E.
TI IS PARTNER CONSENT FOR A WOMAN'S PARTICIPATION IN FERTILITY CLINICAL
TRIALS JUSTIFIED? THE REPRODUCTIVE MEDICINE NETWORK EXPERIENCE.
SO FERTILITY AND STERILITY
LA English
DT Meeting Abstract
CT 68th Annual Meeting of the American-Society-for-Reproductive-Medicine
(ASRM)
CY OCT 20-24, 2012
CL San Diego, CA
SP Amer Soc Reprod Med
C1 [Brzyski, R. G.] Univ Texas HSC San Antonio, San Antonio, TX USA.
[Barnhart, K.] Univ Penn, Med Ctr, Philadelphia, PA 19104 USA.
[Santoro, N.] Univ Colorado, Anschutz Med Campus, Aurora, CO USA.
[Eisenberg, E.] NICHHD, 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 0015-0282
EI 1556-5653
J9 FERTIL STERIL
JI Fertil. Steril.
PD SEP
PY 2012
VL 98
IS 3
SU S
MA O-250
BP S74
EP S74
PG 1
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA V45UY
UT WOS:000209842700247
ER
PT J
AU Calhoun, K
Padilla-Banks, E
VandeVoort, C
Hunt, P
Williams, CJ
AF Calhoun, K.
Padilla-Banks, E.
VandeVoort, C.
Hunt, P.
Williams, C. J.
TI IN THE FETAL RHESUS MONKEY UTERUS, IN UTERO EXPOSURE TO WHOM IT MAY
CONCERN: BISPHENOL A (BPA) IS ASSOCIATED WITH CHANGES IN GENE EXPRESSION
AND ACCELERATED ADENOGENESIS.
SO FERTILITY AND STERILITY
LA English
DT Meeting Abstract
CT 68th Annual Meeting of the American-Society-for-Reproductive-Medicine
(ASRM)
CY OCT 20-24, 2012
CL San Diego, CA
SP Amer Soc Reprod Med
C1 [Calhoun, K.] Univ N Carolina, Div Reprod Endocrinol, Ob Gyn, Chapel Hill, NC USA.
[Padilla-Banks, E.; Williams, C. J.] NIEHS, Reprod Med Grp, Res Triangle Pk, NC 27709 USA.
[Hunt, P.] Washington State Univ, Mol BioSci, Pullman, WA 99164 USA.
[VandeVoort, C.] Univ Calif Davis, Ob Gyn, Davis, CA 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 0015-0282
EI 1556-5653
J9 FERTIL STERIL
JI Fertil. Steril.
PD SEP
PY 2012
VL 98
IS 3
SU S
MA O-106
BP S32
EP S33
PG 2
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA V45UY
UT WOS:000209842700107
ER
PT J
AU Catherino, WH
Malik, M
Britten, J
Levy, G
Gilden, M
AF Catherino, W. H.
Malik, M.
Britten, J.
Levy, G.
Gilden, M.
TI MIFEPRISTONE, A CLINICALLY EFFECTIVE LEIOMYOMA THERAPY, DIRECTLY
REGULATES FIBROSIS IN HUMAN 3-DIMENSIONAL CULTURES.
SO FERTILITY AND STERILITY
LA English
DT Meeting Abstract
C1 [Catherino, W. H.; Malik, M.; Britten, J.; Levy, G.; Gilden, M.] Uniformed Serv Univ Hlth Sci, Obstet & Gynecol, Bethesda, MD 20814 USA.
[Catherino, W. H.; Levy, G.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, Bethesda, MD 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 0015-0282
EI 1556-5653
J9 FERTIL STERIL
JI Fertil. Steril.
PD SEP
PY 2012
VL 98
IS 3
SU S
MA P-408
BP S233
EP S233
PG 1
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA V45UY
UT WOS:000209842700772
ER
PT J
AU Catherino, WH
Malik, M
Britten, J
Gilden, M
AF Catherino, W. H.
Malik, M.
Britten, J.
Gilden, M.
TI RAPAMYCIN, WHICH INHIBITS ESTRADIOL-MEDIATED LEIOMYOMA CELL
PROLIERATION, HAS MINIMAL IMPACT ON FIBROSIS IN HUMAN 3-DIMENSIONAL
CULTURES.
SO FERTILITY AND STERILITY
LA English
DT Meeting Abstract
C1 [Catherino, W. H.; Malik, M.; Britten, J.; Gilden, M.] Uniformed Serv Univ Hlth Sci, Obstet & Gynecol, Bethesda, MD 20814 USA.
[Catherino, W. H.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, Bethesda, MD 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 0015-0282
EI 1556-5653
J9 FERTIL STERIL
JI Fertil. Steril.
PD SEP
PY 2012
VL 98
IS 3
SU S
MA P-407
BP S232
EP S233
PG 2
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA V45UY
UT WOS:000209842700771
ER
PT J
AU Chang, S
Driggers, PH
Malik, M
Wei, Q
Segars, JH
AF Chang, S.
Driggers, P. H.
Malik, M.
Wei, Q.
Segars, J. H.
TI EXPRESSION AND PHOSPHORYLATION OF KEY FOCAL ADHESION PROTEINS DIFFERS IN
UTERINE LEIOMYOMATA AND MYOMETRIUM, AND IS ALTERED BY TREATMENT WITH
ULIPRISTAL ACETATE
SO FERTILITY AND STERILITY
LA English
DT Meeting Abstract
C1 [Chang, S.; Driggers, P. H.; Wei, Q.; Segars, J. H.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD USA.
[Malik, M.] Uniformed Serv Univ Hlth Sci, Obstet & Gynecol, Bethesda, MD 20814 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 0015-0282
EI 1556-5653
J9 FERTIL STERIL
JI Fertil. Steril.
PD SEP
PY 2012
VL 98
IS 3
SU S
MA P-396
BP S229
EP S229
PG 1
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA V45UY
UT WOS:000209842700760
ER
PT J
AU Chason, RJ
Leung, PK
DeCherney, AH
Segars, JH
Catt, KJ
AF Chason, R. J.
Leung, P. K.
DeCherney, A. H.
Segars, J. H.
Catt, K. J.
TI GONADOTROPIN RELEASING HORMONE (GnRH) REDUCES LIGAND-INDUCED ESTROGEN
RECEPTOR (ER) DIMERIZATION IN GT1-7 CELLS
SO FERTILITY AND STERILITY
LA English
DT Meeting Abstract
C1 [Chason, R. J.; Leung, P. K.; DeCherney, A. H.; Segars, J. H.; Catt, K. J.] NICHD, NIH, Bethesda, MD 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 0015-0282
EI 1556-5653
J9 FERTIL STERIL
JI Fertil. Steril.
PD SEP
PY 2012
VL 98
IS 3
SU S
MA P-304
BP S202
EP S202
PG 1
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA V45UY
UT WOS:000209842700670
ER
PT J
AU Cox, JM
Maquire, M
DeCherney, AH
Richter, KS
Levy, M
Henne, MB
AF Cox, J. M.
Maquire, M.
DeCherney, A. H.
Richter, K. S.
Levy, M.
Henne, M. B.
TI CLOMID-GONADOTROPIN OVARIAN HYPERSTIMULATION AND INTRAUTERINE
INSEMINATION: EFFICACY WITH MULTIPLE CYCLES.
SO FERTILITY AND STERILITY
LA English
DT Meeting Abstract
CT 68th Annual Meeting of the American-Society-for-Reproductive-Medicine
(ASRM)
CY OCT 20-24, 2012
CL San Diego, CA
SP Amer Soc Reprod Med
C1 [Maquire, M.; DeCherney, A. H.] NICHD, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD USA.
[Richter, K. S.; Levy, M.] Shady Grove Fertil Reprod Sci Ctr, Rockville, MD USA.
[Cox, J. M.; Henne, M. B.] Walter Reed Natl Mil Med Ctr, Bethesda, MD 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 0015-0282
EI 1556-5653
J9 FERTIL STERIL
JI Fertil. Steril.
PD SEP
PY 2012
VL 98
IS 3
SU S
MA O-8
BP S3
EP S3
PG 1
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA V45UY
UT WOS:000209842700009
ER
PT J
AU Devine, K
Mumford, S
Segars, J
Armstrong, AY
AF Devine, K.
Mumford, S.
Segars, J.
Armstrong, A. Y.
TI IS PRE-ART HYSTEROSCOPIC MYOMECTOMY COST-EFFECTIVE IN WOMEN WITH
SUBMUCOUS (SM) FIBROIDS SEEKING ART?
SO FERTILITY AND STERILITY
LA English
DT Meeting Abstract
C1 [Devine, K.; Segars, J.; Armstrong, A. Y.] NICHD, Program Adult & Reprod Endocrinol, NIH, Bethesda, MD USA.
[Mumford, S.] NICHD, Epidemiol Branch, Div Epidemiol Stat & Prevent Res, NIH, Bethesda, MD USA.
NR 0
TC 1
Z9 1
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0015-0282
EI 1556-5653
J9 FERTIL STERIL
JI Fertil. Steril.
PD SEP
PY 2012
VL 98
IS 3
SU S
MA P-397
BP S229
EP S229
PG 1
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA V45UY
UT WOS:000209842700761
ER
PT J
AU Devine, K
Mumford, S
Hodes-Wertz, B
Druckenmiller, S
Propst, A
Noyes, NN
AF Devine, K.
Mumford, S.
Hodes-Wertz, B.
Druckenmiller, S.
Propst, A.
Noyes, N. N.
TI BABY BUDGETING: A COST-EFFECTIVENESS ANALYSIS (CEA) OF ELECTIVE OOCYTE
CRYOPRESERVATION (EOC) AS A MEANS TO INCREASE LIVE BIRTH RATES (LBR) IN
WOMEN DELAYING REPRODUCTION.
SO FERTILITY AND STERILITY
LA English
DT Meeting Abstract
CT 68th Annual Meeting of the American-Society-for-Reproductive-Medicine
(ASRM)
CY OCT 20-24, 2012
CL San Diego, CA
SP Amer Soc Reprod Med
C1 [Devine, K.] NICHD, Program Adult & Reprod Endocrinol, NIH, Bethesda, MD USA.
[Mumford, S.] NICHD, Epidemiol Branch, Div Epidemiol Stat & Prevent Res, NIH, Bethesda, MD USA.
[Hodes-Wertz, B.; Druckenmiller, S.; Noyes, N. N.] NYU Sch Med, NYU Fertil Ctr, New York, NY USA.
[Propst, A.] Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA.
NR 0
TC 2
Z9 2
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0015-0282
EI 1556-5653
J9 FERTIL STERIL
JI Fertil. Steril.
PD SEP
PY 2012
VL 98
IS 3
SU S
MA O-24
BP S7
EP S8
PG 2
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA V45UY
UT WOS:000209842700025
ER
PT J
AU Duke, CMP
Khachikyan, I
Rosenberg, AZ
Guo, XC
Segars, JH
Armstrong, AY
AF Duke, C. M. P.
Khachikyan, I.
Rosenberg, A. Z.
Guo, X. C.
Segars, J. H.
Armstrong, A. Y.
TI THE PROTECTIVE MECHANISM OF CETRORELIX ACETATE IN A CHEMOTHERAPY-INDUCED
MURINE MODEL OF OVARIAN DAMAGE.
SO FERTILITY AND STERILITY
LA English
DT Meeting Abstract
CT 68th Annual Meeting of the American-Society-for-Reproductive-Medicine
(ASRM)
CY OCT 20-24, 2012
CL San Diego, CA
SP Amer Soc Reprod Med
C1 [Duke, C. M. P.] Johns Hopkins Univ, Sch Med, Gynecol & Obstet, Baltimore, MD USA.
[Khachikyan, I.; Guo, X. C.; Segars, J. H.; Armstrong, A. Y.] NICHHD, Program Reprod & Adult Endocrinol, Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD 20892 USA.
[Rosenberg, A. Z.] NIH, Pathol Lab, Ctr Clin, 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 0015-0282
EI 1556-5653
J9 FERTIL STERIL
JI Fertil. Steril.
PD SEP
PY 2012
VL 98
IS 3
SU S
MA O-236
BP S70
EP S70
PG 1
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA V45UY
UT WOS:000209842700233
ER
PT J
AU Gemmill, JAL
Sinaii, N
Shanis, D
Chrousos, G
Khachikyan, I
Stratton, P
AF Gemmill, J. A. L.
Sinaii, N.
Shanis, D.
Chrousos, G.
Khachikyan, I.
Stratton, P.
TI ASSESSMENT OF THE RELATIONSHIP AMONG MULTIFOCAL PAIN, PAIN SEVERITY,
DISTURBED SLEEP, AND PSYCHOLOGICAL SYMPTOMS IN WOMEN WITH CHRONIC PELVIC
PAIN ASSOCIATED WITH ENDOMETRIOSIS.
SO FERTILITY AND STERILITY
LA English
DT Meeting Abstract
CT 68th Annual Meeting of the American-Society-for-Reproductive-Medicine
(ASRM)
CY OCT 20-24, 2012
CL San Diego, CA
SP Amer Soc Reprod Med
C1 [Gemmill, J. A. L.; Shanis, D.; Chrousos, G.; Khachikyan, I.; Stratton, P.] NICHD, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD USA.
[Sinaii, N.] NIH, Biostat & Clin Epidemiol Serv, CC, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0015-0282
EI 1556-5653
J9 FERTIL STERIL
JI Fertil. Steril.
PD SEP
PY 2012
VL 98
IS 3
SU S
MA O-225
BP S67
EP S67
PG 1
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA V45UY
UT WOS:000209842700222
ER
PT J
AU Green, LJ
Levy, G
Wesley, R
Nieman, L
Armstrong, A
AF Green, L. J.
Levy, G.
Wesley, R.
Nieman, L.
Armstrong, A.
TI EFFICACY OF ULIPRISTAL ACETATE FOR THE TREATMENT OF SYMPTOMATIC UTERINE
LEIOMYOMAS IN AFRICAN AMERICANS.
SO FERTILITY AND STERILITY
LA English
DT Meeting Abstract
CT 68th Annual Meeting of the American-Society-for-Reproductive-Medicine
(ASRM)
CY OCT 20-24, 2012
CL San Diego, CA
SP Amer Soc Reprod Med
C1 [Green, L. J.] Howard Univ Hosp, Obstet & Gynecol, Washington, DC USA.
[Levy, G.; Wesley, R.; Nieman, L.; Armstrong, A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD USA.
NR 0
TC 1
Z9 1
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0015-0282
EI 1556-5653
J9 FERTIL STERIL
JI Fertil. Steril.
PD SEP
PY 2012
VL 98
IS 3
SU S
MA O-323
BP S96
EP S96
PG 1
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA V45UY
UT WOS:000209842700319
ER
PT J
AU Hammoud, AO
Schliep, KC
Mumford, SL
Stanford, JB
Porucznik, CA
Schisterman, EF
AF Hammoud, A. O.
Schliep, K. C.
Mumford, S. L.
Stanford, J. B.
Porucznik, C. A.
Schisterman, E. F.
TI LUTEAL PHASE DEFICIENCY IN NORMAL CYCLING WOMEN.
SO FERTILITY AND STERILITY
LA English
DT Meeting Abstract
CT 68th Annual Meeting of the American-Society-for-Reproductive-Medicine
(ASRM)
CY OCT 20-24, 2012
CL San Diego, CA
SP Amer Soc Reprod Med
C1 [Hammoud, A. O.] Univ Utah, Obstet & Gynecol, Salt Lake City, UT USA.
[Schliep, K. C.; Stanford, J. B.; Porucznik, C. A.] Univ Utah, Family & Prevent Med, Salt Lake City, UT USA.
[Mumford, S. L.; Schisterman, E. F.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, Rockville, MD 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 0015-0282
EI 1556-5653
J9 FERTIL STERIL
JI Fertil. Steril.
PD SEP
PY 2012
VL 98
IS 3
SU S
MA O-82
BP S25
EP S26
PG 2
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA V45UY
UT WOS:000209842700083
ER
PT J
AU Hill, MJ
Heitmann, RJ
Richter, K
Graham, JR
DeCherney, AH
Levy, MJ
AF Hill, M. J.
Heitmann, R. J.
Richter, K.
Graham, J. R.
DeCherney, A. H.
Levy, M. J.
TI THE NUMBER OF SUPERNUMERARY VITRIFIED BLASTOCYSTS IS POSITIVELY
CORRELATED TO IMPLANTATION IN SINGLE BLASTOCYST TRANSFERS.
SO FERTILITY AND STERILITY
LA English
DT Meeting Abstract
CT 68th Annual Meeting of the American-Society-for-Reproductive-Medicine
(ASRM)
CY OCT 20-24, 2012
CL San Diego, CA
SP Amer Soc Reprod Med
C1 [Hill, M. J.; Heitmann, R. J.; Richter, K.; Graham, J. R.; Levy, M. J.] Shady Grove Fertil Reprod Sci Ctr, Rockville, MD USA.
[Hill, M. J.; Heitmann, R. J.; DeCherney, A. H.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD 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 0015-0282
EI 1556-5653
J9 FERTIL STERIL
JI Fertil. Steril.
PD SEP
PY 2012
VL 98
IS 3
SU S
MA O-346
BP S102
EP S103
PG 2
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA V45UY
UT WOS:000209842700341
ER
PT J
AU Hill, MJ
Heitmann, RJ
Richter, K
Graham, JR
DeCherney, AH
Widra, E
AF Hill, M. J.
Heitmann, R. J.
Richter, K.
Graham, J. R.
DeCherney, A. H.
Widra, E.
TI THE SIMPLIFIED SART EMBRYO SCORING SYSTEM IS HIGHLY CORRELATED TO
IMPLANTATION AND LIVE BIRTH IN SINGLE BLASTOCYST TRANSFERS.
SO FERTILITY AND STERILITY
LA English
DT Meeting Abstract
C1 [Hill, M. J.; Heitmann, R. J.; Richter, K.; Graham, J. R.; Widra, E.] Shady Grove Fertil Reprod Sci Ctr, Rockville, MD USA.
[Hill, M. J.; Heitmann, R. J.; DeCherney, A. H.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD 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 0015-0282
EI 1556-5653
J9 FERTIL STERIL
JI Fertil. Steril.
PD SEP
PY 2012
VL 98
IS 3
SU S
MA P-533
BP S269
EP S269
PG 1
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA V45UY
UT WOS:000209842700891
ER
PT J
AU Hill, MJ
Levens, ED
Richter, K
Graham, JR
DeCherney, AH
Browne, PE
AF Hill, M. J.
Levens, E. D.
Richter, K.
Graham, J. R.
DeCherney, A. H.
Browne, P. E.
TI TROPHECTODERM GRADE, BUT NOT INNER CELL MASS GRADE, IS PREDICTIVE OF
OUTCOMES IN SINGLE BLASTOCYST TRANSFERS.
SO FERTILITY AND STERILITY
LA English
DT Meeting Abstract
CT 68th Annual Meeting of the American-Society-for-Reproductive-Medicine
(ASRM)
CY OCT 20-24, 2012
CL San Diego, CA
SP Amer Soc Reprod Med
C1 [Hill, M. J.; Levens, E. D.; Richter, K.; Graham, J. R.; Browne, P. E.] Shady Grove Fertil Reprod Sci Ctr, Rockville, MD USA.
[Hill, M. J.; Levens, E. D.; DeCherney, A. H.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD 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 0015-0282
EI 1556-5653
J9 FERTIL STERIL
JI Fertil. Steril.
PD SEP
PY 2012
VL 98
IS 3
SU S
MA O-331
BP S98
EP S98
PG 1
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA V45UY
UT WOS:000209842700327
ER
PT J
AU Hill, MJ
Levy, G
Richter, K
DeCherney, A
Suthar, G
Levy, MJ
AF Hill, M. J.
Levy, G.
Richter, K.
DeCherney, A.
Suthar, G.
Levy, M. J.
TI ELEVATED SERUM PROGESTERONE ON THE DAY OF HUMAN CHORIONIC GONADOTROPIN
(hCG) TRIGGER NEGATIVELY IMPACTS IMPLANTATION IN BOTH CLEAVAGE AND
BLASTOCYST EMBRYO TRANSFERS.
SO FERTILITY AND STERILITY
LA English
DT Meeting Abstract
CT 68th Annual Meeting of the American-Society-for-Reproductive-Medicine
(ASRM)
CY OCT 20-24, 2012
CL San Diego, CA
SP Amer Soc Reprod Med
C1 [Hill, M. J.; Levy, G.; Richter, K.; Suthar, G.; Levy, M. J.] Shady Grove Fertil Reprod Sci Ctr, Rockville, MD USA.
[Hill, M. J.; Levy, G.; DeCherney, A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD 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 0015-0282
EI 1556-5653
J9 FERTIL STERIL
JI Fertil. Steril.
PD SEP
PY 2012
VL 98
IS 3
SU S
MA O-281
BP S83
EP S84
PG 2
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA V45UY
UT WOS:000209842700277
ER
PT J
AU Jorge, S
Driggers, PH
Malik, M
Segars, JH
AF Jorge, S.
Driggers, P. H.
Malik, M.
Segars, J. H.
TI AKAP13 AUGMENTS PROGESTERONE-DEPENDENT GENE ACTIVATION IN FIBROID CELLS
SO FERTILITY AND STERILITY
LA English
DT Meeting Abstract
CT 68th Annual Meeting of the American-Society-for-Reproductive-Medicine
(ASRM)
CY OCT 20-24, 2012
CL San Diego, CA
SP Amer Soc Reprod Med
C1 [Jorge, S.; Driggers, P. H.; Segars, J. H.] NICHD, Program Adult & Reprod Endocrinol, NIH, Bethesda, MD USA.
[Malik, M.] USUHS, Dept ObGyn, Bethesda, MD 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 0015-0282
EI 1556-5653
J9 FERTIL STERIL
JI Fertil. Steril.
PD SEP
PY 2012
VL 98
IS 3
SU S
MA O-238
BP S71
EP S71
PG 1
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA V45UY
UT WOS:000209842700235
ER
PT J
AU Levy, G
Malik, M
Britten, J
Gilden, M
Segars, JH
Catherino, WH
AF Levy, G.
Malik, M.
Britten, J.
Gilden, M.
Segars, J. H.
Catherino, W. H.
TI LIAROZOLE REDUCES TGF-beta 3 MEDIATED FIBROSIS IN 2-DIMENSIONAL AND
3-DIMENSIONAL LEIOMYOMA CULTURES.
SO FERTILITY AND STERILITY
LA English
DT Meeting Abstract
C1 [Levy, G.; Segars, J. H.; Catherino, W. H.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, Bethesda, MD USA.
[Levy, G.; Malik, M.; Britten, J.; Gilden, M.; Catherino, W. H.] Uniformed Serv Univ Hlth Sci, Dept Ob Gyn, Bethesda, MD 20814 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 0015-0282
EI 1556-5653
J9 FERTIL STERIL
JI Fertil. Steril.
PD SEP
PY 2012
VL 98
IS 3
SU S
MA P-401
BP S230
EP S231
PG 2
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA V45UY
UT WOS:000209842700765
ER
PT J
AU Levy, G
Hill, MJ
Comeaux, T
Beall, S
Segars, JH
Csokmay, J
AF Levy, G.
Hill, M. J.
Comeaux, T.
Beall, S.
Segars, J. H.
Csokmay, J.
TI SERUM HUMAN CHORIONIC GONADOTROPIN DOES NOT CORRELATE WITH OOCYTE
MATURITY
SO FERTILITY AND STERILITY
LA English
DT Meeting Abstract
C1 [Levy, G.; Hill, M. J.; Beall, S.; Segars, J. H.; Csokmay, J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD USA.
[Comeaux, T.; Csokmay, J.] Bayne Jones Army Community Hosp, Dept Ob Gyn, Ft Polk, LA 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 0015-0282
EI 1556-5653
J9 FERTIL STERIL
JI Fertil. Steril.
PD SEP
PY 2012
VL 98
IS 3
SU S
MA P-567
BP S279
EP S279
PG 1
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA V45UY
UT WOS:000209842700924
ER
PT J
AU Libfraind, LL
Richter, KS
Wolff, EF
Geddes, K
Levy, MJ
AF Libfraind, L. L.
Richter, K. S.
Wolff, E. F.
Geddes, K.
Levy, M. J.
TI A SHARED RISK (SR) REFUND PROGRAM FOR IN VITRO FERTILIZATION (IVF)
TREATMENT RECEIVES STRONG ENDORSEMENT FROM PARTICIPANTS.
SO FERTILITY AND STERILITY
LA English
DT Meeting Abstract
C1 [Libfraind, L. L.; Wolff, E. F.] NIH, Bethesda, MD 20892 USA.
[Richter, K. S.; Geddes, K.; Levy, M. J.] Shady Grove Fertil Reprod Sci Ctr, Rockville, MD 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 0015-0282
EI 1556-5653
J9 FERTIL STERIL
JI Fertil. Steril.
PD SEP
PY 2012
VL 98
IS 3
SU S
MA P-423
BP S237
EP S237
PG 1
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA V45UY
UT WOS:000209842700787
ER
PT J
AU Malik, M
Britten-Webb, J
Catherino, WH
AF Malik, M.
Britten-Webb, J.
Catherino, W. H.
TI LEIOMYOMA CELL REGULATION VIA THE PROFIBROBLASTIC PROTEIN LAMININ,
RESULTS IN SPATIAL ORGANIZATION
SO FERTILITY AND STERILITY
LA English
DT Meeting Abstract
CT 68th Annual Meeting of the American-Society-for-Reproductive-Medicine
(ASRM)
CY OCT 20-24, 2012
CL San Diego, CA
SP Amer Soc Reprod Med
C1 [Malik, M.; Britten-Webb, J.; Catherino, W. H.] USUHS, Obstet & Gynecol, Bethesda, MD USA.
[Catherino, W. H.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, Bethesda, MD 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 0015-0282
EI 1556-5653
J9 FERTIL STERIL
JI Fertil. Steril.
PD SEP
PY 2012
VL 98
IS 3
SU S
MA O-237
BP S71
EP S71
PG 1
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA V45UY
UT WOS:000209842700234
ER
PT J
AU Malik, M
Britten-Webb, J
Levy, G
Gilden, M
Catherino, WH
AF Malik, M.
Britten-Webb, J.
Levy, G.
Gilden, M.
Catherino, W. H.
TI TGFBETA MEDIATED FIBROSIS IN LEIOMYOMA CELLS WORKS THROUGH THE SMAD
DEPENDENT SIGNALING AND NOT THROUGH MAPK/ERK PATHWAY
SO FERTILITY AND STERILITY
LA English
DT Meeting Abstract
CT 68th Annual Meeting of the American-Society-for-Reproductive-Medicine
(ASRM)
CY OCT 20-24, 2012
CL San Diego, CA
SP Amer Soc Reprod Med
C1 [Malik, M.; Britten-Webb, J.; Levy, G.; Gilden, M.; Catherino, W. H.] USUHS, Obstet & Gynecol, Bethesda, MD USA.
[Levy, G.; Catherino, W. H.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, Bethesda, MD 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 0015-0282
EI 1556-5653
J9 FERTIL STERIL
JI Fertil. Steril.
PD SEP
PY 2012
VL 98
IS 3
SU S
MA O-243
BP S72
EP S72
PG 1
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA V45UY
UT WOS:000209842700240
ER
PT J
AU Muneyyirci-Delale, O
Charles, C
Sinaii, N
Anopa, J
Dalloul, M
Stratton, P
AF Muneyyirci-Delale, O.
Charles, C.
Sinaii, N.
Anopa, J.
Dalloul, M.
Stratton, P.
TI CHANGES IN SELF-REPORTED SYMPTOMS OF WOMEN WITH ENDOMETRIOSIS DURING
TREATMENT.
SO FERTILITY AND STERILITY
LA English
DT Meeting Abstract
C1 [Muneyyirci-Delale, O.; Charles, C.; Anopa, J.; Dalloul, M.] Suny Downstate Med Ctr, Obstet & Gynecol, Brooklyn, NY 11203 USA.
[Muneyyirci-Delale, O.] Kings Cty Hosp Ctr, Obstet & Gynecol, Brooklyn, NY USA.
[Sinaii, N.] NIH, Biostat & Clin Epidemiol Serv, Ctr Clin, Bethesda, MD 20892 USA.
[Stratton, P.] NICHD, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD 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 0015-0282
EI 1556-5653
J9 FERTIL STERIL
JI Fertil. Steril.
PD SEP
PY 2012
VL 98
IS 3
SU S
MA P-346
BP S215
EP S215
PG 1
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA V45UY
UT WOS:000209842700712
ER
PT J
AU Pal, L
Williams, J
AF Pal, L.
Williams, J.
CA Reprod Med Network Investigators
TI VITAMIN D (VitD) STATUS PREDICTS PCOS RELATED INFERTILITY TREATMENT
SUCCESS: RETROSPECTIVE COHORT ANALYSIS OF 25OHD LEVELS IN STORED SERA
FROM A RCT OF CLOMID (CC) VS. METFORMIN (M) VS. (CC plus M) IN PCOS
SO FERTILITY AND STERILITY
LA English
DT Meeting Abstract
CT 68th Annual Meeting of the American-Society-for-Reproductive-Medicine
(ASRM)
CY OCT 20-24, 2012
CL San Diego, CA
SP Amer Soc Reprod Med
C1 [Pal, L.; Williams, J.] Yale Univ, Obstet Gynecol & Reprod Sci, New Haven, CT USA.
[Reprod Med Network Investigators] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD 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 0015-0282
EI 1556-5653
J9 FERTIL STERIL
JI Fertil. Steril.
PD SEP
PY 2012
VL 98
IS 3
SU S
BP S62
EP S62
PG 1
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA V45UY
UT WOS:000209842700206
ER
PT J
AU Stanford, JB
Schliep, KC
Chen, Z
Xie, Y
Louis, GMB
Peterson, CM
AF Stanford, J. B.
Schliep, K. C.
Chen, Z.
Xie, Y.
Louis, G. M. Buck
Peterson, C. M.
TI COMPARABILITY OF ENDOMETRIOSIS DIAGNOSIS AND STAGING BY OPERATING
SURGEON AND EXPERT REVIEWER DURING REAL-TIME LAPAROSCOPY IN THE ENDO
STUDY.
SO FERTILITY AND STERILITY
LA English
DT Meeting Abstract
C1 [Stanford, J. B.; Schliep, K. C.] Univ Utah, Family & Prevent Med, Salt Lake City, UT USA.
[Chen, Z.; Xie, Y.; Louis, G. M. Buck] NICHHD, Div Epidemiol Stat & Prevent Res, Rockville, MD USA.
[Peterson, C. M.] Univ Utah, Obstet & Gynecol, Salt Lake City, UT 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 0015-0282
EI 1556-5653
J9 FERTIL STERIL
JI Fertil. Steril.
PD SEP
PY 2012
VL 98
IS 3
SU S
MA P-352
BP S216
EP S216
PG 1
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA V45UY
UT WOS:000209842700718
ER
PT J
AU Yu, B
DeCherney, A
Segars, J
Ignaszewski, A
Russanova, V
Howard, B
AF Yu, B.
DeCherney, A.
Segars, J., Jr.
Ignaszewski, A.
Russanova, V.
Howard, B.
TI DIMINISHED OVARIAN FUNCTION IS ASSOCIATED WITH DISTINCTIVE DNA METHYLOME
CHANGES IN HUMAN OVARIAN GRANULOSA CELLS
SO FERTILITY AND STERILITY
LA English
DT Meeting Abstract
CT 68th Annual Meeting of the American-Society-for-Reproductive-Medicine
(ASRM)
CY OCT 20-24, 2012
CL San Diego, CA
SP Amer Soc Reprod Med
C1 [Yu, B.; DeCherney, A.; Segars, J., Jr.] NICHD, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD USA.
[Ignaszewski, A.] Shady Grove Fertil Reprod Sci Ctr, Embryol Lab, Rockville, MD USA.
[Russanova, V.; Howard, B.] NICHD, Program Genom Differentiat, NIH, Bethesda, MD 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 0015-0282
EI 1556-5653
J9 FERTIL STERIL
JI Fertil. Steril.
PD SEP
PY 2012
VL 98
IS 3
SU S
MA O-197
BP S59
EP S59
PG 1
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA V45UY
UT WOS:000209842700195
ER
PT J
AU Ariza, J
Jodar, L
Mercken, EM
Carboneau, B
de Cabo, R
Villalba, JM
AF Ariza, J.
Jodar, L.
Mercken, E. M.
Carboneau, B.
de Cabo, R.
Villalba, J. M.
TI Hormetic response via Nrf2 in mice with a genetic deletion of the
antioxidant enzyme NQO1
SO FREE RADICAL BIOLOGY AND MEDICINE
LA English
DT Meeting Abstract
DE Nrf2; NQO1; Oxidative stress; Hormesis
C1 [Ariza, J.; Jodar, L.; Villalba, J. M.] Univ Cordoba, E-14071 Cordoba, Spain.
[Mercken, E. M.; Carboneau, B.; de Cabo, R.] NIA, Lab Expt Gerontol, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 2
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0891-5849
EI 1873-4596
J9 FREE RADICAL BIO MED
JI Free Radic. Biol. Med.
PD SEP
PY 2012
VL 53
SU 1
MA 0524
BP S126
EP S127
DI 10.1016/j.freeradbiomed.2012.08.264
PG 2
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA V40LT
UT WOS:000209480800261
ER
PT J
AU Finkel, T
AF Finkel, T.
TI Oxidants, DNA damage and stem cell function
SO FREE RADICAL BIOLOGY AND MEDICINE
LA English
DT Meeting Abstract
C1 [Finkel, T.] NIH, New York, NY 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 0891-5849
EI 1873-4596
J9 FREE RADICAL BIO MED
JI Free Radic. Biol. Med.
PD SEP
PY 2012
VL 53
SU 1
MA 6.4
BP S15
EP S15
DI 10.1016/j.freeradbiomed.2012.08.102
PG 1
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA V40LT
UT WOS:000209480800031
ER
PT J
AU Nagababu, E
AF Nagababu, E.
TI Glutathione-hemin complex catalyzes S-nitrosothiol formation under
hypoxia conditions
SO FREE RADICAL BIOLOGY AND MEDICINE
LA English
DT Meeting Abstract
DE S-nitrosothiols; Nitric oxide; hemin; Glutathione
C1 [Nagababu, E.] NIA, Bethesda, MD 20892 USA.
NR 0
TC 1
Z9 1
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0891-5849
EI 1873-4596
J9 FREE RADICAL BIO MED
JI Free Radic. Biol. Med.
PD SEP
PY 2012
VL 53
SU 1
MA 0650
BP S189
EP S189
DI 10.1016/j.freeradbiomed.2012.08.397
PG 1
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA V40LT
UT WOS:000209480800393
ER
PT J
AU Scott, I
Webster, BR
Sack, MN
AF Scott, I.
Webster, B. R.
Sack, M. N.
TI A conserved prokaryotic region of GCN5L1 is required for mitochondrial
acetyltransferase function
SO FREE RADICAL BIOLOGY AND MEDICINE
LA English
DT Meeting Abstract
DE Mitochondria; Acetyltransferase; GCN5L1; SIRT3
C1 [Scott, I.; Webster, B. R.; Sack, M. N.] NHLBI, Bethesda, MD 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 0891-5849
EI 1873-4596
J9 FREE RADICAL BIO MED
JI Free Radic. Biol. Med.
PD SEP
PY 2012
VL 53
SU 1
MA 6
BP S37
EP S38
DI 10.1016/j.freeradbiomed.2012.08.500
PG 2
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA V40LT
UT WOS:000209480800078
ER
PT J
AU Summers, FA
Mason, RP
Ehrenshaft, M
AF Summers, F. A.
Mason, R. P.
Ehrenshaft, M.
TI DNA radical detection using immunoblotting
SO FREE RADICAL BIOLOGY AND MEDICINE
LA English
DT Meeting Abstract
DE DNA; oxidation; immuno-spin trapping; peroxiredoxin
C1 [Summers, F. A.; Mason, R. P.; Ehrenshaft, M.] NIEHS, Res Triangle Pk, NC 27709 USA.
NR 1
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 0891-5849
EI 1873-4596
J9 FREE RADICAL BIO MED
JI Free Radic. Biol. Med.
PD SEP
PY 2012
VL 53
SU 1
MA 0223
BP S218
EP S218
DI 10.1016/j.freeradbiomed.2012.08.457
PG 1
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA V40LT
UT WOS:000209480800453
ER
PT J
AU Koonin, EV
Wolf, YI
AF Koonin, Eugene V.
Wolf, Yuri I.
TI Evolution of microbes and viruses: a paradigm shift in evolutionary
biology?
SO FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
LA English
DT Review
DE Darwin; modern synthesis; comparative genomics; tree of life; horizontal
gene transfer
ID HORIZONTAL GENE-TRANSFER; DIVERSITY-GENERATING RETROELEMENTS;
ESCHERICHIA-COLI O157-H7; TRANSFER-RNA SYNTHETASES; GENOME EVOLUTION;
TRANSPOSABLE ELEMENTS; PHYLOGENETIC TREES; MULLERS RATCHET;
NEISSERIA-GONORRHOEAE; BACTERIAL EVOLUTION
AB When Charles Darwin formulated the central principles of evolutionary biology in the Origin of Species in 1859 and the architects of the Modern Synthesis integrated these principles with population genetics almost a century later, the principal if not the sole objects of evolutionary biology were multicellular eukaryotes, primarily animals and plants. Before the advent of efficient gene sequencing, all attempts to extend evolutionary studies to bacteria have been futile. Sequencing of the r-RNA genes in thousands of microbes allowed the construction of the three- domain "ribosomal Tree of Life" that was widely thought to have resolved the evolutionary relationships between the cellular life forms. However, subsequent massive sequencing of numerous, complete microbial genomes revealed novel evolutionary phenomena, the most fundamental of these being: (1) pervasive horizontal gene transfer (HGT), in large part mediated by viruses and plasmids, that shapes the genomes of archaea and bacteria and call for a radical revision (if not abandonment) of the Tree of Life concept, (2) Lamarckian-type inheritance that appears to be critical for antivirus defense and other forms of adaptation in prokaryotes, and (3) evolution of evolvability, i.e., dedicated mechanisms for evolution such as vehicles for HGT and stress-induced mutagenesis systems. In the non-cellular part of the microbial world, phylogenomics and metagenomics of viruses and related selfish genetic elements revealed enormous genetic and molecular diversity and extremely high abundance of viruses that come across as the dominant biological entities on earth. Furthermore, the perennial arms race between viruses and their hosts is one of the defining factors of evolution. Thus, microbial phylogenomics adds new dimensions to the fundamental picture of evolution even as the principle of descent with modification discovered by Darwin and the laws of population genetics remain at the core of evolutionary biology.
C1 [Koonin, Eugene V.; Wolf, Yuri I.] Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA.
RP Koonin, EV (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, 8600 Rockville Pike,NIH Bldg 38a, Bethesda, MD 20894 USA.
EM koonin@ncbi.nlm.nih.gov
FU US Department of Health and Human Services
FX The authors research is supported by intramural funds of the US
Department of Health and Human Services (to National Library of
Medicine, NIH).
NR 202
TC 40
Z9 43
U1 4
U2 88
PU FRONTIERS RESEARCH FOUNDATION
PI LAUSANNE
PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND
SN 2235-2988
J9 FRONT CELL INFECT MI
JI Front. Cell. Infect. Microbiol.
PD SEP
PY 2012
VL 2
AR UNSP 119
DI 10.3389/fcimb.2012.00119
PG 15
WC Immunology; Microbiology
SC Immunology; Microbiology
GA 221BI
UT WOS:000324631800005
PM 22993722
ER
PT J
AU Gomez, J
AF Gomez, J.
TI MOLECULAR PROFILING OF STAGE II AND III BREAST CANCER IN LATIN AMERICAN
WOMEN RECEIVING STANDARD-OF-CARE TREATMENT
SO INTERNATIONAL JOURNAL OF BEHAVIORAL MEDICINE
LA English
DT Meeting Abstract
DE cancer genetics
C1 [Gomez, J.] NCI, Off Latin Amer Canc Program Dev US LACRN, Washington, DC USA.
EM gallion@uthscsa.edu
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1070-5503
EI 1532-7558
J9 INT J BEHAV MED
JI Int. J. Behav. Med.
PD SEP
PY 2012
VL 19
SU 1
MA S187
BP S75
EP S75
PG 1
WC Psychology, Clinical
SC Psychology
GA V45KR
UT WOS:000209816000183
ER
PT J
AU Groffen, DAI
Bosma, H
Koster, A
Von Bonsdorff, MB
Eiriksdottir, G
Aspelund, T
Penninx, BW
Kempen, GI
Kirschbaum, C
Harris, TB
Gudnason, V
AF Groffen, D. A. I.
Bosma, H.
Koster, A.
Von Bonsdorff, M. B.
Eiriksdottir, G.
Aspelund, T.
Penninx, B. W.
Kempen, G. I.
Kirschbaum, C.
Harris, T. B.
Gudnason, V.
TI EDUCATIONAL LEVEL, SALIVARY CORTISOL, AND ALL CAUSE MORTALITY IN AN
OLDER POPULATION. RESULTS FROM THE AGES-REYKJAVIK STUDY
SO INTERNATIONAL JOURNAL OF BEHAVIORAL MEDICINE
LA English
DT Meeting Abstract
C1 [Groffen, D. A. I.; Bosma, H.; Koster, A.] Maastricht Univ, Dept Social Med, CAPHRI Sch Publ Hlth & Primary Care, Maastricht, Netherlands.
[Von Bonsdorff, M. B.] Gerontol Res Ctr, Dept Hlth Sci, Jyvaskyla, Finland.
[Eiriksdottir, G.; Aspelund, T.; Gudnason, V.] Iceland Heart Assoc, Reykjavik, Iceland.
[Penninx, B. W.] Vrije Univ Amsterdam, Med Ctr, Dept Psychiat, EMGO Inst Hlth & Care Res, Amsterdam, Netherlands.
[Kempen, G. I.] Maastricht Univ, Dept Hlth Serv Res, CAPHRI Sch Publ Hlth & Primary Care, Maastricht, Netherlands.
[Kirschbaum, C.] Tech Univ Dresden, Biol Psychol, Dresden, Germany.
[Harris, T. B.] NIA, NIH, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA.
EM d.groffen@maastrichtuniversity.nl
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1070-5503
EI 1532-7558
J9 INT J BEHAV MED
JI Int. J. Behav. Med.
PD SEP
PY 2012
VL 19
SU 1
MA O785
BP S316
EP S316
PG 1
WC Psychology, Clinical
SC Psychology
GA V45KR
UT WOS:000209816000757
ER
PT J
AU Kaufmann, PG
Powell, LH
Freedland, KE
AF Kaufmann, P. G.
Powell, L. H.
Freedland, K. E.
TI DESIGN AND EXECUTION OF RANDOMIZED CLINICAL TRIALS INVOLVING BEHAVIORAL
INTERVENTIONS - Part I.
SO INTERNATIONAL JOURNAL OF BEHAVIORAL MEDICINE
LA English
DT Meeting Abstract
C1 [Kaufmann, P. G.] NHLBI, Bethesda, MD 20892 USA.
[Powell, L. H.] Rush Univ, Med Ctr, Chicago, IL 60612 USA.
[Freedland, K. E.] Washington Univ, St Louis, MO USA.
EM kaufmann@nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1070-5503
EI 1532-7558
J9 INT J BEHAV MED
JI Int. J. Behav. Med.
PD SEP
PY 2012
VL 19
SU 1
MA 1
BP S1
EP S1
PG 1
WC Psychology, Clinical
SC Psychology
GA V45KR
UT WOS:000209816000002
ER
PT J
AU Kaufmann, PG
Powell, LH
Freedland, KE
AF Kaufmann, P. G.
Powell, L. H.
Freedland, K. E.
TI DESIGN AND EXECUTION OF RANDOMIZED CLINICAL TRIALS INVOLVING BEHAVIORAL
INTERVENTIONS - PART II.
SO INTERNATIONAL JOURNAL OF BEHAVIORAL MEDICINE
LA English
DT Meeting Abstract
C1 [Kaufmann, P. G.] NHLBI, Bethesda, MD 20892 USA.
[Powell, L. H.] Rush Univ, Med Ctr, Chicago, IL 60612 USA.
[Freedland, K. E.] Washington Univ, St Louis, MO USA.
EM kaufmann@nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1070-5503
EI 1532-7558
J9 INT J BEHAV MED
JI Int. J. Behav. Med.
PD SEP
PY 2012
VL 19
SU 1
MA 6
BP S2
EP S2
PG 1
WC Psychology, Clinical
SC Psychology
GA V45KR
UT WOS:000209816000006
ER
PT J
AU McBride, M
Persky
Wagner, K
Faith, S
Ward, S
AF McBride, M.
Persky
Wagner, K.
Faith, S.
Ward, S.
TI USING A VIRTUAL REALITY BUFFET TO ASSESS MOTHERS' BEHAVIORAL RESPONSES
TO FAMILY HISTORY ASSESSMENT OF THEIR CHILDREN'S RISK FOR OBESITY
SO INTERNATIONAL JOURNAL OF BEHAVIORAL MEDICINE
LA English
DT Meeting Abstract
DE eating behaviors; children's health; genetics
C1 [McBride, M.; Persky] NIH, Social & Behav Res Branch, Bethesda, MD 20892 USA.
[Wagner, K.] Univ North Carolina Chapel Hill, Hlth Behav & Hlth Educ, Chapel Hill, NC USA.
[Faith, S.; Ward, S.] Univ North Carolina Chapel Hill, Nutr, Chapel Hill, NC USA.
EM cmcbride@mail.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1070-5503
EI 1532-7558
J9 INT J BEHAV MED
JI Int. J. Behav. Med.
PD SEP
PY 2012
VL 19
SU 1
MA O549
BP S219
EP S219
PG 1
WC Psychology, Clinical
SC Psychology
GA V45KR
UT WOS:000209816000529
ER
PT J
AU Evans, S
Almahdi, B
Sultan, P
Sohanpal, I
Brandner, B
Collier, T
Shergill, SS
Cregg, R
Averbeck, BB
AF Evans, Simon
Almahdi, Basil
Sultan, Pervez
Sohanpal, Imrat
Brandner, Brigitta
Collier, Tracey
Shergill, Sukhi S.
Cregg, Roman
Averbeck, Bruno B.
TI Performance on a probabilistic inference task in healthy subjects
receiving ketamine compared with patients with schizophrenia
SO JOURNAL OF PSYCHOPHARMACOLOGY
LA English
DT Article
DE Ketamine; decision making; schizophrenia
ID STRIATAL DOPAMINE; REASONING BIASES; THOUGHT-DISORDER; LINKING BIOLOGY;
WORKING-MEMORY; PSYCHOSIS; DELUSIONS; VOLUNTEERS; CONCLUSIONS; COGNITION
AB Evidence suggests that some aspects of schizophrenia can be induced in healthy volunteers through acute administration of the non-competitive NMDA-receptor antagonist, ketamine. In probabilistic inference tasks, patients with schizophrenia have been shown to 'jump to conclusions' (JTC) when asked to make a decision. We aimed to test whether healthy participants receiving ketamine would adopt a JTC response pattern resembling that of patients. The paradigmatic task used to investigate JTC has been the 'urn' task, where participants are shown a sequence of beads drawn from one of two 'urns', each containing coloured beads in different proportions. Participants make a decision when they think they know the urn from which beads are being drawn. We compared performance on the urn task between controls receiving acute ketamine or placebo with that of patients with schizophrenia and another group of controls matched to the patient group. Patients were shown to exhibit a JTC response pattern relative to their matched controls, whereas JTC was not evident in controls receiving ketamine relative to placebo. Ketamine does not appear to promote JTC in healthy controls, suggesting that ketamine does not affect probabilistic inferences.
C1 [Evans, Simon; Averbeck, Bruno B.] UCL, Inst Neurol, Sobell Dept Motor Neurosci & Movement Disorders, London WC1N 3BG, England.
[Almahdi, Basil; Sultan, Pervez; Sohanpal, Imrat; Brandner, Brigitta; Cregg, Roman] Univ Coll Hosp, London, England.
[Shergill, Sukhi S.] Kings Coll London, Inst Psychiat, Dept Psychiat, Cognit Schizophrenia & Imaging Lab, London, England.
[Averbeck, Bruno B.] NIMH, Neuropsychol Lab, NIH, Bethesda, MD 20892 USA.
RP Evans, S (reprint author), UCL, Inst Neurol, Sobell Dept Motor Neurosci & Movement Disorders, London WC1N 3BG, England.
EM sle27@sussex.ac.uk
FU MRC; Wellcome Trust
FX This work was supported by an MRC studentship to SE and a Wellcome Trust
grant to BA.
NR 51
TC 8
Z9 8
U1 3
U2 7
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 0269-8811
EI 1461-7285
J9 J PSYCHOPHARMACOL
JI J. Psychopharmacol.
PD SEP
PY 2012
VL 26
IS 9
BP 1211
EP 1217
DI 10.1177/0269881111435252
PG 7
WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA 982CE
UT WOS:000307018500006
PM 22389244
ER
PT J
AU Kong, A
Beresford, SAA
Alfano, CM
Schubert, KEF
Neuhouser, ML
Johnson, DB
Duggan, C
Wang, CY
Xiao, LR
Jeffery, RW
Bain, CE
McTiernan, A
AF Kong, Angela
Beresford, Shirley A. A.
Alfano, Catherine M.
Schubert, Karen E. Foster
Neuhouser, Marian L.
Johnson, Donna B.
Duggan, Catherine
Wang, Ching-Yun
Xiao, Liren
Jeffery, Robert W.
Bain, Carolyn E.
McTiernan, Anne
TI Self-Monitoring and Eating-Related Behaviors Are Associated with
12-Month Weight Loss in Postmenopausal Overweight-to-Obese Women
SO JOURNAL OF THE ACADEMY OF NUTRITION AND DIETETICS
LA English
DT Article
DE Women; Behavioral strategies; Eating behaviors; Weight loss
AB Lifestyle-based interventions, which typically promote various behavior modification strategies, can serve as a setting for evaluating specific behaviors and strategies thought to promote or hinder weight loss. The aim of our study was to test the associations of self-monitoring (ie, self-weighing and food journal completion) and eating-related (ie, dietary intake, diet-related weight-control strategies, and meal patterns) behaviors with weight loss in a sample of postmenopausal overweight-to-obese women enrolled in a 12-month dietary weight loss intervention. Changes in body weight and adoption of self-monitoring and eating-related behaviors were assessed in 123 participants. Generalized linear models tested associations of these behaviors with 12-month weight change after adjusting for potential confounders. Mean percent weight loss was 10.7%. In the final model, completing more food journals was associated with a greater percent weight loss (interquartile range 3.7% greater weight loss; P<0.0001), whereas skipping meals (4.3% lower weight loss; P<0.05) and eating out for lunch (at least once a week, 2.5% lower weight loss; P<0.01) were associated with a lower amount of weight loss. These findings suggest that a greater focus on dietary self-monitoring, home-prepared meals, and consuming meals at regular intervals may improve 12-month weight loss among postmenopausal women enrolled in a dietary weight loss intervention.
C1 [Kong, Angela] Univ Illinois, Inst Hlth Res & Policy, Canc Educ & Career Dev Program, Chicago, IL USA.
[Beresford, Shirley A. A.; Schubert, Karen E. Foster; Johnson, Donna B.] Univ Washington, Ctr Publ Hlth Nutr, Seattle, WA 98195 USA.
[Alfano, Catherine M.] NCI, Off Canc Survivorship, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Neuhouser, Marian L.] Fred Hutchinson Canc Res Ctr, Canc Prevent Program, Seattle, WA 98109 USA.
[Duggan, Catherine; McTiernan, Anne] Fred Hutchinson Canc Res Ctr, Prevent Ctr, Seattle, WA 98109 USA.
[McTiernan, Anne] Fred Hutchinson Canc Res Ctr, Program Epidemiol, Seattle, WA 98109 USA.
[Xiao, Liren; Bain, Carolyn E.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA.
[Jeffery, Robert W.] Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN USA.
RP McTiernan, A (reprint author), Fred Hutchinson Canc Res Ctr, Prevent Ctr, M4-B874,POB 19024, Seattle, WA 98109 USA.
EM amctiern@fhcrc.org
RI Duggan, Catherine/F-9414-2015
OI Duggan, Catherine/0000-0001-7369-4021
FU National Cancer Institute [R01 CA105204-01A1, U54-CA116847, R25CA094880,
2R25CA057699]; National Center for Research Resources [5KL2RR025015-03]
FX This work was supported by grant nos. R01 CA105204-01A1, U54-CA116847,
R25CA094880, and 2R25CA057699 from the National Cancer Institute and no.
5KL2RR025015-03 from the National Center for Research Resources.
NR 54
TC 14
Z9 14
U1 1
U2 15
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 2212-2672
EI 2212-2680
J9 J ACAD NUTR DIET
JI J. Acad. Nutr. Diet.
PD SEP
PY 2012
VL 112
IS 9
BP 1428
EP 1435
DI 10.1016/j.jand.2012.05.014
PG 8
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA V33ZV
UT WOS:000209057600019
PM 22795495
ER
PT J
AU Glasgow, RE
Kurz, D
Dickman, JM
Osuna, D
Strycker, L
King, DK
AF Glasgow, Russell E.
Kurz, Deanna
Dickman, Jennifer M.
Osuna, Diego
Strycker, Lisa
King, Diane K.
TI Linking internet-based diabetes self-management to primary care: lessons
learned and implications for research translation and practice
implementation
SO TRANSLATIONAL BEHAVIORAL MEDICINE
LA English
DT Article
DE Implementation; Primary care; Chronic disease self-management;
Integration; Health technology
AB There has been little discussion of or research on the key translational issue of how to integrate patient self-management programs across multiple primary care clinics within an HMO. The purpose of this study was to summarize our experiences and lessons learned in trying to integrate information from a web-based diabetes self-management program into primary care and the electronic health record (EHR). We describe plans, implementation, adaptations made, and data on patient and physician reactions to the My Path diabetes self-management program provided to 331 adult primary care patients. Mixed methods results revealed that, despite the availability of a state-of-the-art EHR, the intervention was not well integrated into primary care. Information from health-promotion and disease management programs, even within the same organization and with advanced EHR systems, is challenging to integrate into busy primary care.
C1 [Glasgow, Russell E.] NCI, Div Canc Control & Populat Sci, Rockville, MD 20852 USA.
[Kurz, Deanna; Dickman, Jennifer M.; Osuna, Diego] Kaiser Permanente Colorado, Denver, CO USA.
[Strycker, Lisa] Oregon Res Inst, Eugene, OR 97403 USA.
[King, Diane K.] Univ Alaska, Fairbanks, AK 99701 USA.
RP Glasgow, RE (reprint author), NCI, Div Canc Control & Populat Sci, 6130 Execut Blvd,Room 6144, Rockville, MD 20852 USA.
EM glasgowre@mail.nih.gov
FU National Institute of Diabetes and Digestive and Kidney Diseases
[DK35524]
FX This paper is dedicated to the memory of Dr. Osuna, whose commitment to
reducing health disparities and to integrating research and practice was
an inspiration to us. This study was supported by grant DK35524 from the
National Institute of Diabetes and Digestive and Kidney Diseases. All
authors declare no conflicts of interest. Dr. Glasgow is now Deputy
Director for Implementation Science, Division of Cancer Control and
Population Sciences, National Cancer Institute. The opinions in this
article do not necessarily represent those of the National Cancer
Institute or any other body.
NR 33
TC 1
Z9 1
U1 2
U2 4
PU SPRINGER INTERNATIONAL PUBLISHING AG
PI CHAM
PA GEWERBESTRASSE 11, CHAM, CH-6330, SWITZERLAND
SN 1869-6716
EI 1613-9860
J9 TRANSL BEHAV MED
JI Transl. Behav. Med.
PD SEP
PY 2012
VL 2
IS 3
BP 313
EP 321
DI 10.1007/s13142-012-0109-8
PG 9
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA V39LM
UT WOS:000209412500013
PM 24073131
ER
PT J
AU Nagpal, R
Kumar, A
Kumar, M
Behare, PV
Jain, S
Yadav, H
AF Nagpal, Ravinder
Kumar, Ashwani
Kumar, Manoj
Behare, Pradip V.
Jain, Shalini
Yadav, Hariom
TI Probiotics, their health benefits and applications for developing
healthier foods: a review
SO FEMS MICROBIOLOGY LETTERS
LA English
DT Review
DE dairy foods; functional foods; gut microbial communities; lactic acid
bacteria; lactobacillus; probiotics
ID LACTIC-ACID-BACTERIA; LACTOBACILLUS-ACIDOPHILUS NCFM; RHAMNOSUS STRAIN
GG; COLON CARCINOGENESIS; HUMAN GUT; IN-VITRO; BIFIDOBACTERIUM-LONGUM;
GASTROINTESTINAL-TRACT; GROWTH-CHARACTERISTICS; INTESTINAL MICROFLORA
AB In the industrialized world, functional foods have become a part of an everyday diet and are demonstrated to offer potential health benefits beyond the widely accepted nutritional effects. Currently, the most important and frequently used functional food compounds are probiotics and prebiotics, or they are collectively known as synbiotics. Moreover, with an already healthy image, dairy products appear to be an excellent mean for inventing nutritious foods. Such probiotic dairy foods beneficially affect the host by improving survival and implantation of live microbial dietary supplements in the gastrointestinal flora, by selectively stimulating the growth or activating the catabolism of one or a limited number of health-promoting bacteria in the intestinal tract, and by improving the gastrointestinal tract's microbial balance. Hence, the paper reviews the current scenario of probiotics and their prospective potential applications for functional foods for better health and nutrition of the society.
C1 [Nagpal, Ravinder] Shaheed Udham Singh Coll Res & Technol, Dept Microbiol & Biotechnol, Mohali, Punjab, India.
[Kumar, Ashwani] Seth Jai Parkash Mukand Lal Inst Engn & Technol, Dept Biotechnol, Radaur, Haryana, India.
[Kumar, Manoj] Natl Inst Nutr, Dept Microbiol & Immunol, Hyderabad 500007, Andhra Pradesh, India.
[Behare, Pradip V.] Natl Dairy Res Inst, Dairy Microbiol Div, Karnal 132001, Haryana, India.
[Jain, Shalini; Yadav, Hariom] NIDDKD, NIH, Bethesda, MD 20892 USA.
RP Kumar, A (reprint author), JMIT, Dept Biotechnol, Radaur 135133, Haryana, India.
EM ashwanindri@rediffmail.com
OI Yadav, Hariom/0000-0003-4504-1597
NR 119
TC 53
Z9 61
U1 12
U2 133
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0378-1097
EI 1574-6968
J9 FEMS MICROBIOL LETT
JI FEMS Microbiol. Lett.
PD SEP
PY 2012
VL 334
IS 1
BP 1
EP 15
DI 10.1111/j.1574-6968.2012.02593.x
PG 15
WC Microbiology
SC Microbiology
GA 981XX
UT WOS:000307007200001
PM 22568660
ER
PT J
AU Beydoun, HA
Beydoun, MA
Kaufman, JS
Lo, B
Zonderman, AB
AF Beydoun, Hind A.
Beydoun, May A.
Kaufman, Jay S.
Lo, Bruce
Zonderman, Alan B.
TI Intimate partner violence against adult women and its association with
major depressive disorder, depressive symptoms and postpartum
depression: A systematic review and meta-analysis
SO SOCIAL SCIENCE & MEDICINE
LA English
DT Review
DE USA; Women; Intimate partner violence; Major depressive disorder;
Elevated depressive symptoms; Postpartum depression; Meta-analysis
ID ATTENDING GENERAL-PRACTICE; AFRICAN-AMERICAN WOMEN; MENTAL-HEALTH;
SUBSTANCE-ABUSE; SOCIAL SUPPORT; CARE SETTINGS; LATINA WOMEN;
RISK-FACTOR; LOW-INCOME; PREVALENCE
AB To date, few systematic reviews of observational studies have been conducted to comprehensively evaluate the co-morbidity of intimate partner violence (IPV) and specific depression outcomes in women. In this systematic review and meta-analysis, we summarize the extant literature and estimate the magnitude of the association between IPV and key depressive outcomes (elevated depressive symptoms, diagnosed major depressive disorder and postpartum depression). PubMed (January 1, 1980-December 31, 2010) searches of English-language observational studies were conducted. Most of the selected 37 studies had cross-sectional population-based designs, focused on elevated depressive symptoms and were conducted in the United States. Most studies suggested moderate or strong positive associations between IPV and depression. Our meta-analysis suggested two to three-fold increased risk of major depressive disorder and 1.5-2-fold increased risk of elevated depressive symptoms and postpartum depression among women exposed to intimate partner violence relative to non-exposed women. A sizable proportion (9%-28%) of major depressive disorder, elevated depressive symptoms, and postpartum depression can be attributed to lifetime exposure to IPV. In an effort to reduce the burden of depression, continued research is recommended for evaluating IPV preventive strategies. (c) 2012 Elsevier Ltd. All rights reserved.
C1 [Beydoun, Hind A.] Eastern Virginia Med Sch, Grad Program Publ Hlth, Norfolk, VA 23501 USA.
[Beydoun, May A.; Zonderman, Alan B.] NIA, Lab Behav Neurosci, NIH, IRP, Baltimore, MD 21224 USA.
[Kaufman, Jay S.] McGill Univ, Dept Epidemiol Biostat & Occupat Hlth, Montreal, PQ, Canada.
[Lo, Bruce] Eastern Virginia Med Sch, Dept Emergency Med, Norfolk, VA 23501 USA.
RP Beydoun, HA (reprint author), Eastern Virginia Med Sch, Grad Program Publ Hlth, POB 1980, Norfolk, VA 23501 USA.
EM baydouha@evms.edu
OI Kaufman, Jay/0000-0003-1606-401X; Zonderman, Alan B/0000-0002-6523-4778
FU Intramural NIH HHS [Z01 AG000513-08]
NR 100
TC 75
Z9 77
U1 12
U2 65
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0277-9536
J9 SOC SCI MED
JI Soc. Sci. Med.
PD SEP
PY 2012
VL 75
IS 6
BP 959
EP 975
DI 10.1016/j.socscimed.2012.04.025
PG 17
WC Public, Environmental & Occupational Health; Social Sciences, Biomedical
SC Public, Environmental & Occupational Health; Biomedical Social Sciences
GA 979LQ
UT WOS:000306821900002
PM 22694991
ER
PT J
AU Choi, KY
Jeon, EJ
Yoon, HY
Lee, BS
Na, JH
Min, KH
Kim, SY
Myung, SJ
Lee, S
Chen, XY
Kwon, IC
Choi, K
Jeong, SY
Kim, K
Park, JH
AF Choi, Ki Young
Jeon, Eun Jung
Yoon, Hong Yeol
Lee, Beom Suk
Na, Jin Hee
Min, Kyung Hyun
Kim, Sang Yoon
Myung, Seung-Jae
Lee, Seulki
Chen, Xiaoyuan
Kwon, Ick Chan
Choi, Kuiwon
Jeong, Seo Young
Kim, Kwangmeyung
Park, Jae Hyung
TI Theranostic nanoparticles based on PEGylated hyaluronic acid for the
diagnosis, therapy and monitoring of colon cancer
SO BIOMATERIALS
LA English
DT Article
DE Hyaluronic acid; Nanoparticle; Theranostics; Irinotecan; Colon cancer;
Tumor targeting
ID METASTATIC COLORECTAL-CANCER; 1ST-LINE TREATMENT; FLUOROURACIL;
LEUCOVORIN; CARCINOMA; COLONOSCOPIES; NEOPLASIA; TUMORS; AGENT; TRIAL
AB Colon cancer is the second leading cause of cancer-related death in the United States. The considerable mortality from colon cancer is due to metastasis to other organs, mainly the liver. In the management of colon cancer, early detection and targeted therapy are crucial. In this study, we aimed to establish a versatile theranostic system for early tumor detection and targeted tumor therapy by using poly(ethylene glycol)-conjugated hyaluronic acid nanoparticles (P-HA-NPs) which can selectively accumulate in tumor tissue. For the diagnostic application, a near-infrared fluorescence (NIRF) imaging dye (Cy 5.5) was chemically conjugated onto the HA backbone of P-HA-NPs. After intravenous injection of Cy5.5-P-HA-NPs into the tumor-bearing mice, small-sized colon tumors as well as liver-implanted colon tumors were effectively visualized using the NIRF imaging technique. For targeted therapy, we physically encapsulated the anticancer drug, irinotecan (IRT), into the hydrophobic cores of P-HA-NPs. Owing to their notable tumor targeting capability, IRT-P-HA-NPs exhibited an excellent antitumor activity while showing a reduction in undesirable systemic toxicity. Importantly, we demonstrated the theranostic application using Cy5.5-P-HA-NPs and IRT-P-HA-NPs in orthotopic colon cancer models. Following the systemic administration of Cy5.5-P-HA-NPs, neoplasia was clearly visualized, and the tumor growth was effectively suppressed by intravenous injection of IRT-P-HA-NPs. It should be emphasized that the therapeutic responses could be simultaneously monitored by Cy5.5-P-HA-NPs. Our results suggest that P-HA-NPs can be used as a versatile theranostic system for the early detection, targeted therapy, and therapeutic monitoring of colon cancer. (C) 2012 Elsevier Ltd. All rights reserved.
C1 [Park, Jae Hyung] Sungkyunkwan Univ, Dept Polymer Sci & Engn, Theranost Macromol Res Ctr, Suwon 440746, South Korea.
[Choi, Ki Young; Yoon, Hong Yeol; Lee, Beom Suk; Na, Jin Hee; Min, Kyung Hyun; Kim, Sang Yoon; Kwon, Ick Chan; Choi, Kuiwon; Kim, Kwangmeyung] Korea Inst Sci & Technol, Biomed Res Inst, Seoul 136791, South Korea.
[Choi, Ki Young; Lee, Seulki; Chen, Xiaoyuan] NIBIB, Lab Mol Imaging & Nanomed LOMIN, NIH, Bethesda, MD 20892 USA.
[Jeon, Eun Jung] Catholic Univ Korea, Sch Med, Dept Internal Med, Seoul, South Korea.
[Lee, Beom Suk; Kim, Sang Yoon] Univ Ulsan, Coll Med, Asan Med Ctr, Dept Otolaryngol, Seoul 138736, South Korea.
[Na, Jin Hee; Min, Kyung Hyun; Jeong, Seo Young] Kyung Hee Univ, Dept Life & Nanopharmaceut Sci, Seoul 130701, South Korea.
[Myung, Seung-Jae] Univ Ulsan, Coll Med, Asan Med Ctr, Dept Internal Med, Seoul 138736, South Korea.
[Myung, Seung-Jae] Univ Ulsan, Coll Med, Asan Med Ctr, Asan Digest Dis Res Inst, Seoul 138736, South Korea.
RP Park, JH (reprint author), Sungkyunkwan Univ, Dept Polymer Sci & Engn, Theranost Macromol Res Ctr, 300 Sheoncheon Dong, Suwon 440746, South Korea.
EM kim@kist.re.kr; jhpark1@skku.edu
RI byun, jaehyun/G-5584-2014; Yoon, Hong Yeol/A-2413-2016; CHOI, KI
YOUNG/Q-7177-2016; Yoon, Hong Yeol/D-4005-2017;
OI Yoon, Hong Yeol/0000-0003-3242-3633; Myung,
Seung-Jae/0000-0003-0585-4016
FU Korea Healthcare Technology RD Project [A101706-1001-0000200]; Global
Research Laboratory (GRL) Project; Converging Research Program
[20090081876]; Basic Science Research Programs of MEST [20100027955,
2012012827]
FX This work was financially supported by the Korea Healthcare Technology
R&D Project (A101706-1001-0000200) of MW, the Global Research Laboratory
(GRL) Project, the Converging Research Program (20090081876), and the
Basic Science Research Programs (20100027955 & 2012012827) of MEST.
NR 35
TC 61
Z9 64
U1 19
U2 105
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0142-9612
J9 BIOMATERIALS
JI Biomaterials
PD SEP
PY 2012
VL 33
IS 26
BP 6186
EP 6193
DI 10.1016/j.biomaterials.2012.05.029
PG 8
WC Engineering, Biomedical; Materials Science, Biomaterials
SC Engineering; Materials Science
GA 978DI
UT WOS:000306720400022
PM 22687759
ER
PT J
AU Chauvet, C
Goldberg, SR
Jaber, M
Solinas, M
AF Chauvet, Claudia
Goldberg, Steven R.
Jaber, Mohamed
Solinas, Marcello
TI Effects of environmental enrichment on the incubation of cocaine craving
SO NEUROPHARMACOLOGY
LA English
DT Article
DE Addiction; Treatment; Relapse; Neuroadaptation; Stress; Withdrawal
ID DRUG-ABUSE; RATS; REINSTATEMENT; EXPRESSION; WITHDRAWAL; SEEKING;
STRESS; SENSITIZATION; ADDICTION; RELAPSE
AB Recent studies have demonstrated that exposure to environmental enrichment (EE) during withdrawal periods reduces the risks of relapse to drug-seeking behavior. In this study, we investigated whether EE could prevent the development of time-dependent increases in cocaine-seeking behavior (incubation of craving). In addition, we investigated whether EE could eliminate already developed incubation and whether the effects of EE would last when enrichment is discontinued. For this, we allowed rats to self-administer cocaine for 10 daily 6 h sessions and measured cocaine-seeking 1,30 and 60 days after the last self-administration session. In between these tests, rats were kept in forced abstinence and housed either in EE or standard environments (SE). Between day 30 and 60 of withdrawal, half of the rats in each group were maintained in their original environmental condition and the other half was switched to the other environmental condition. We found that exposure to EE prevents development of incubation of cocaine craving and eliminates already developed incubation. In addition, contrary to our expectations, when EE was discontinued, its positive effects on incubation of craving disappeared. These results indicate that EE can reduce cocaine seeking but only temporarily and questions the hypothesis that EE can permanently eliminate the neural consequences of exposure to drugs of abuse. Therefore, stimulating environments could have positive effects on the treatment of cocaine addiction only if they are maintained for long periods of abstinence that encompass the time-frame during which addicts are most vulnerable to relapse. (C) 2012 Elsevier Ltd. All rights reserved.
C1 [Solinas, Marcello] Univ Poitiers, Neurobiol & Neuropharmacol Addict Grp, Expt & Clin Neurosci Lab, INSERM,U1084, F-86022 Poitiers, France.
[Goldberg, Steven R.] NIDA, Preclin Pharmacol Sect, Behav Neurosci Res Branch, Intramural Res Program,NIH,Dept Hlth & Human Serv, Baltimore, MD 21224 USA.
RP Solinas, M (reprint author), Univ Poitiers, Neurobiol & Neuropharmacol Addict Grp, Expt & Clin Neurosci Lab, INSERM,U1084, 1 Rue George Bonnet, F-86022 Poitiers, France.
EM marcello.solinas@univ-poitiers.fr
RI Solinas, Marcello/M-3500-2016
OI Solinas, Marcello/0000-0002-0664-5964
FU Centre National pour la Recherche Scientifique; University of Poitiers;
Mission Interministerielle de la Lutte contre les Drogues et la
Toxicomanie; Region Poitou Charentes; CPER 5 (Contrat de Projet
Etat-Region); Intramural Research Program of the National Institute on
Drug Abuse, National Institutes of Health, Department of Health and
Human Services; French Ministry of Research
FX We thank N Thiriet and J Nader for their helpful discussion and C
Nicolas and J. Vejoux for help with the experiments. This work was
supported by Centre National pour la Recherche Scientifique, University
of Poitiers, Mission Interministerielle de la Lutte contre les Drogues
et la Toxicomanie (MILDT-INSERM, 2006-2007 and MILDT-INSERM-INCA
2007-2009), Region Poitou Charentes, CPER 5 (Contrat de Projet
Etat-Region) and the Intramural Research Program of the National
Institute on Drug Abuse, National Institutes of Health, Department of
Health and Human Services. C Chauvet was a recipient of a PhD fellowship
from the French Ministry of Research.
NR 37
TC 23
Z9 23
U1 2
U2 7
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0028-3908
J9 NEUROPHARMACOLOGY
JI Neuropharmacology
PD SEP
PY 2012
VL 63
IS 4
BP 635
EP 641
DI 10.1016/j.neuropharm.2012.05.014
PG 7
WC Neurosciences; Pharmacology & Pharmacy
SC Neurosciences & Neurology; Pharmacology & Pharmacy
GA 977DX
UT WOS:000306637700015
PM 22634364
ER
PT J
AU Tranah, GJ
Lam, ET
Katzman, SM
Nalls, MA
Zhao, YQ
Evans, DS
Yokoyama, JS
Pawlikowska, L
Kwok, PY
Mooney, S
Kritchevsky, S
Goodpaster, BH
Newman, AB
Harris, TB
Manini, TM
Cummings, SR
AF Tranah, Gregory J.
Lam, Ernest T.
Katzman, Shana M.
Nalls, Michael A.
Zhao, Yiqiang
Evans, Daniel S.
Yokoyama, Jennifer S.
Pawlikowska, Ludmila
Kwok, Pui-Yan
Mooney, Sean
Kritchevsky, Stephen
Goodpaster, Bret H.
Newman, Anne B.
Harris, Tamara B.
Manini, Todd M.
Cummings, Steven R.
CA Hlth Aging Body Composition Study
TI Mitochondrial DNA sequence variation is associated with free-living
activity energy expenditure in the elderly
SO BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS
LA English
DT Article
DE Metabolic rate; Energy expenditure; Mitochondria; mtDNA; Oxidative
phosphorylation; DNA sequencing
ID HEREDITARY OPTIC NEUROPATHY; HUMAN SKELETAL-MUSCLE;
CYTOCHROME-C-OXIDASE; GENOME-WIDE ASSOCIATION; RESPIRATORY-CHAIN
FUNCTION; AMINO-ACID SUBSTITUTIONS; AGE-DEPENDENT INCREASE; RESTING
METABOLIC-RATE; AGING HUMAN TISSUES; PHYSICAL-ACTIVITY
AB The decline in activity energy expenditure underlies a range of age-associated pathological conditions, neuromuscular and neurological impairments, disability, and mortality. The majority (90%) of the energy needs of the human body are met by mitochondrial oxidative phosphorylation (OXPHOS). OXPHOS is dependent on the coordinated expression and interaction of genes encoded in the nuclear and mitochondria! genomes. We examined the role of mitochondrial genomic variation in free-living activity energy expenditure (AEE) and physical activity levels (PAL) by sequencing the entire (similar to 16.5 kilobases) mtDNA from 138 Health. Aging, and Body Composition Study participants. Among the common mtDNA variants, the hypervariable region 2 m.185G>A variant was significantly associated with AEE (p = 0.001) and PAL (p = 0.0005) after adjustment for multiple comparisons. Several unique nonsynonymous variants were identified in the extremes of AEE with some occurring at highly conserved sites predicted to affect protein structure and function. Of interest is the p.T194M, CytB substitution in the lower extreme of AEE occurring at a residue in the Qi site of complex III. Among participants with low activity levels, the burden of singleton variants was 30% higher across the entire mtDNA and OXPHOS complex I when compared to those having moderate to high activity levels. A significant pooled variant association across the hypervariable 2 region was observed for AEE and PAL These results suggest that mtDNA variation is associated with free-living AEE in older persons and may generate new hypotheses by which specific mtDNA complexes, genes, and variants may contribute to the maintenance of activity levels in late life. Published by Elsevier B.V.
C1 [Tranah, Gregory J.] UCSF, San Francisco Coordinating Ctr, Calif Pacific Med Ctr Res Inst, San Francisco, CA 94107 USA.
[Lam, Ernest T.; Kwok, Pui-Yan] Univ Calif San Francisco, Inst Human Genet, San Francisco, CA 94143 USA.
[Katzman, Shana M.; Zhao, Yiqiang; Mooney, Sean] Buck Inst Res Aging, Novato, CA 94945 USA.
[Nalls, Michael A.] NIA, Neurogenet Lab, Intramural Res Program, Bethesda, MD 20892 USA.
[Yokoyama, Jennifer S.] Univ Calif San Francisco, Dept Neurol, Memory & Aging Ctr, San Francisco, CA 94143 USA.
[Pawlikowska, Ludmila] Univ Calif San Francisco, Dept Anesthesia & Perioperat Care, San Francisco, CA 94143 USA.
[Kritchevsky, Stephen] Wake Forest Sch Med, Sticht Ctr Aging, Winston Salem, NC 27157 USA.
[Goodpaster, Bret H.] Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA 15213 USA.
[Newman, Anne B.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15213 USA.
[Harris, Tamara B.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD USA.
[Manini, Todd M.] Univ Florida, Dept Aging & Geriatr Res, Gainesville, FL 32601 USA.
RP Tranah, GJ (reprint author), UCSF, San Francisco Coordinating Ctr, Calif Pacific Med Ctr Res Inst, 185 Berry St,Lobby 5,Suite 5700, San Francisco, CA 94107 USA.
EM gtranah@sfcc-cpmc.edu
RI Kwok, Pui-Yan/F-7725-2014; Newman, Anne/C-6408-2013;
OI Kwok, Pui-Yan/0000-0002-5087-3059; Newman, Anne/0000-0002-0106-1150;
Kritchevsky, Stephen/0000-0003-3336-6781
FU National Institute on Aging (NIA) [N01-AG-6-2101, N01-AG-6-2103,
N01-AG-6-2106, R01-AG028050, R03-AG032498]; NINR [R01-NR012459]; NIH
[T32 GM007175]; NLM [LM009722]; [Z01A6000932]
FX This research was supported by National Institute on Aging (NIA)
Contracts N01-AG-6-2101; N01-AG-6-2103; and N01-AG-6-2106; NIA grants
R01-AG028050 and R03-AG032498, NINR grant R01-NR012459; and Z01A6000932.
E.T.L. was supported in part by NIH Training Grant T32 GM007175 and Y.Z.
by NLM grant LM009722. Data analyses for this study utilized the
high-performance computational capabilities of the Biowulf Linux cluster
at the National Institutes of Health, Bethesda, Maryland
(http://biowulf.nih.gov).
NR 151
TC 6
Z9 6
U1 0
U2 8
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0005-2728
J9 BBA-BIOENERGETICS
JI Biochim. Biophys. Acta-Bioenerg.
PD SEP
PY 2012
VL 1817
IS 9
BP 1691
EP 1700
DI 10.1016/j.bbabio.2012.05.012
PG 10
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 975UG
UT WOS:000306536400017
PM 22659402
ER
PT J
AU Shiba, Y
Randazzo, PA
AF Shiba, Yoko
Randazzo, Paul A.
TI ArfGAP1 function in COPI mediated membrane traffic: Currently debated
models and comparison to other coat-binding ArfGAPs
SO HISTOLOGY AND HISTOPATHOLOGY
LA English
DT Review
DE ArfGAP1; Arf1; Golgi apparatus; Retrograde traffic; Coatomer; COPI
ID ADP-RIBOSYLATION FACTOR; GTPASE-ACTIVATING PROTEIN; NUCLEOTIDE-EXCHANGE
FACTORS; TRANS-GOLGI NETWORK; CELL-FREE SYSTEM;
SACCHAROMYCES-CEREVISIAE; ARF GAPS; FACTOR-I; SORTING SIGNALS;
SUCCESSIVE COMPARTMENTS
AB The ArfGAPs are a family of proteins containing an ArfGAP catalytic domain that induces the hydrolysis of GTP bound to the small guanine nucleotide binding-protein ADP-ribosylation factor (Arf). Functional models for Arfs, which are regulators of membrane traffic, are based on the idea that guanine nucleotide-binding proteins function as switches: Arf with GTP bound is active and binds to effector proteins; the conversion of GTP to GDP inactivates Arf. The cellular activities of ArfGAPs have been examined primarily as regulatory proteins that inactivate Arf; however, Arf function in membrane traffic does not strictly adhere to the concept of a simple switch, adding complexity to models explaining the role of ArfGAPs. Here, we review the literature addressing the function Arf and ArfGAP1 in COPI mediated transport, focusing on two critical and integrated functions of membrane traffic, cargo sorting and vesicle coat polymerization. We briefly discuss other ArfGAPs that may have similar function in Arf-dependent membrane traffic outside the ER-Golgi.
C1 [Shiba, Yoko; Randazzo, Paul A.] NCI, Lab Cellular & Mol Biol, Bethesda, MD 20892 USA.
RP Randazzo, PA (reprint author), NCI, Lab Cellular & Mol Biol, Bldg 37,Room 2042, Bethesda, MD 20892 USA.
EM randazzp@mail.nih.gov
FU National Cancer Institute, National Institutes of Health
FX The authors thank Julie Donaldson for critically reading the manuscript.
The work was supported by the Intramural Program of the National Cancer
Institute, National Institutes of Health.
NR 100
TC 4
Z9 4
U1 2
U2 15
PU F HERNANDEZ
PI MURCIA
PA PLAZA FUENSANTA 2-7 C, 30008 MURCIA, SPAIN
SN 0213-3911
EI 1699-5848
J9 HISTOL HISTOPATHOL
JI Histol. Histopath.
PD SEP
PY 2012
VL 27
IS 9
BP 1143
EP 1153
PG 11
WC Cell Biology; Pathology
SC Cell Biology; Pathology
GA 975OU
UT WOS:000306521400003
PM 22806901
ER
PT J
AU Walters, AD
Bommakanti, A
Cohen-Fix, O
AF Walters, Alison D.
Bommakanti, Ananth
Cohen-Fix, Orna
TI Shaping the nucleus: Factors and forces
SO JOURNAL OF CELLULAR BIOCHEMISTRY
LA English
DT Article
DE NUCLEAR SHAPE; ENDOPLASMIC RETICULUM; MITOSIS; NUCLEAR ENVELOPE;
LAMINOPATHIES
ID SPINDLE POLE BODY; ENDOPLASMIC-RETICULUM; MEMBRANE-PROTEINS;
SACCHAROMYCES-CEREVISIAE; PORE COMPLEXES; ENVELOPE ENVIRONMENT;
MAMMALIAN-CELLS; FISSION YEAST; GENOME; SIZE
AB Take a look at a textbook illustration of a cell and you will immediately be able to locate the nucleus, which is often drawn as a spherical or ovoid shaped structure. But not all cells have such nuclei. In fact, some disease states are diagnosed by the presence of nuclei that have an abnormal shape or size. What defines nuclear shape and nuclear size, and how does nuclear geometry affect nuclear function? While the answer to the latter question remains largely unknown, significant progress has been made towards understanding the former. In this review, we provide an overview of the factors and forces that affect nuclear shape and size, discuss the relationship between ER structure and nuclear morphology, and speculate on the possible connection between nuclear size and its shape. We also note the many interesting questions that remain to be explored. J. Cell. Biochem. 113: 28132821, 2012. (C) 2012 Wiley Periodicals, Inc.
C1 [Walters, Alison D.; Bommakanti, Ananth; Cohen-Fix, Orna] NIDDK, Lab Cell & Mol Biol, NIH, Bethesda, MD 20892 USA.
RP Cohen-Fix, O (reprint author), 8 Ctr Dr,Bldg 8,Room 319, Bethesda, MD 20892 USA.
EM ornacf@helix.nih.gov
FU National Institutes of Diabetes and Digestive and Kidney Diseases
FX Grant sponsor: National Institutes of Diabetes and Digestive and Kidney
Diseases.
NR 90
TC 28
Z9 29
U1 3
U2 26
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0730-2312
J9 J CELL BIOCHEM
JI J. Cell. Biochem.
PD SEP
PY 2012
VL 113
IS 9
BP 2813
EP 2821
DI 10.1002/jcb.24178
PG 9
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 972QQ
UT WOS:000306292700003
PM 22566057
ER
PT J
AU Light, AC
Zhu, YL
Shi, J
Saszik, S
Lindstrom, S
Davidson, L
Li, XY
Chiodo, VA
Hauswirth, WW
Li, W
DeVries, SH
AF Light, Adam C.
Zhu, Yongling
Shi, Jun
Saszik, Shannon
Lindstrom, Sarah
Davidson, Laura
Li, Xiaoyu
Chiodo, Vince A.
Hauswirth, William W.
Li, Wei
DeVries, Steven H.
TI Organizational motifs for ground squirrel cone bipolar cells
SO JOURNAL OF COMPARATIVE NEUROLOGY
LA English
DT Article
DE ground squirrel; adeno-associated virus; inner plexiform layer; retina
ID RETINAL GANGLION-CELLS; MACAQUE MONKEY RETINA; INNER PLEXIFORM LAYER;
AII AMACRINE CELLS; MAMMALIAN RETINA; MOUSE RETINA; RABBIT RETINA;
PRIMATE RETINA; IMMUNOCYTOCHEMICAL ANALYSIS; CHOLINE-ACETYLTRANSFERASE
AB In daylight vision, parallel processing starts at the cone synapse. Cone signals flow to On and Off bipolar cells, which are further divided into types according to morphology, immunocytochemistry, and function. The axons of the bipolar cell types stratify at different levels in the inner plexiform layer (IPL) and can interact with costratifying amacrine and ganglion cells. These interactions endow the ganglion cell types with unique functional properties. The wiring that underlies the interactions among bipolar, amacrine, and ganglion cells is poorly understood. It may be easier to elucidate this wiring if organizational rules can be established. We identify 13 types of cone bipolar cells in the ground squirrel, 11 of which contact contiguous cones, with the possible exception of short-wavelength-sensitive cones. Cells were identified by antibody labeling, tracer filling, and Golgi-like filling following transduction with an adeno-associated virus encoding for green fluorescent protein. The 11 bipolar cell types displayed two organizational patterns. In the first pattern, eight to 10 of the 11 types came in pairs with partially overlapping axonal stratification. Pairs shared morphological, immunocytochemical, and functional properties. The existence of similar pairs is a new motif that might have implications for how signals first diverge from a cone to bipolar cells and then reconverge onto a costratifying ganglion cell. The second pattern is a mirror symmetric organization about the middle of the IPL involving at least seven bipolar cell types. This anatomical symmetry may be associated with a functional symmetry in On and Off ganglion cell responses. J. Comp. Neurol. 520:28642887, 2012. (c) 2012 Wiley Periodicals Inc.
C1 [Light, Adam C.; Zhu, Yongling; Shi, Jun; Saszik, Shannon; Lindstrom, Sarah; Davidson, Laura; Li, Xiaoyu; DeVries, Steven H.] Northwestern Univ, Dept Ophthalmol, Feinberg Sch Med, Chicago, IL 60611 USA.
[Chiodo, Vince A.; Hauswirth, William W.] Univ Florida, Dept Ophthalmol, Gainesville, FL 32610 USA.
[Li, Wei] NEI, Unit Retinal Neurophysiol, NIH, Bethesda, MD 20892 USA.
RP DeVries, SH (reprint author), Northwestern Univ, Dept Ophthalmol, Feinberg Sch Med, Tarry 5-715,300 E Super St, Chicago, IL 60611 USA.
EM s-devries@northwestern.edu
RI shi, jun/C-2389-2011;
OI Lindstrom, Sarah H./0000-0001-7952-8120
FU National Institutes of Health [R01EY018204, R01EY012141, R01EY11123,
P30EY021721]; Research to Prevent Blindness; Macular Vision Research
Foundation; Foundation Fighting Blindness; Eldon Family Foundation;
Vision for Children
FX Grant sponsor: National Institutes of Health; Grant numbers:
R01EY018204, R01EY012141 (to S. H. D.), R01EY11123 (to W. W. H.),
P30EY021721 (to W. W. H.); Grant sponsors: Research to Prevent Blindness
(to S. H. D., W. W. H.), Macular Vision Research Foundation (to W. W.
H.), Foundation Fighting Blindness (to W. W. H.), Eldon Family
Foundation (to W. W. H.), Vision for Children (to W.W.H.).
NR 82
TC 17
Z9 17
U1 0
U2 6
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0021-9967
J9 J COMP NEUROL
JI J. Comp. Neurol.
PD SEP 1
PY 2012
VL 520
IS 13
BP 2864
EP 2887
DI 10.1002/cne.23068
PG 24
WC Neurosciences; Zoology
SC Neurosciences & Neurology; Zoology
GA 970LF
UT WOS:000306129500004
PM 22778006
ER
PT J
AU Gorlick, R
Maris, JM
Houghton, PJ
Lock, R
Carol, H
Kurmasheva, RT
Kolb, EA
Keir, ST
Reynolds, CP
Kang, MH
Billups, CA
Smith, MA
AF Gorlick, Richard
Maris, John M.
Houghton, Peter J.
Lock, Richard
Carol, Hernan
Kurmasheva, Raushan T.
Kolb, E. Anders
Keir, Stephen T.
Reynolds, C. Patrick
Kang, Min H.
Billups, Catherine A.
Smith, Malcolm A.
TI Testing of the Akt/PKB inhibitor MK-2206 by the pediatric preclinical
testing program
SO PEDIATRIC BLOOD & CANCER
LA English
DT Article
DE developmental therapeutics; MK-2206; preclinical testing
ID ACUTE LYMPHOBLASTIC-LEUKEMIA; HUMAN NEUROBLASTOMA-CELLS; GROWTH-FACTOR;
3-KINASE PATHWAY; AKT INHIBITOR; IN-VITRO; CANCER; CHEMOTHERAPY;
ACTIVATION; SURVIVAL
AB Background MK-2206 is a small molecule allosteric inhibitor of Akt/PKB that is undergoing clinical trials for treatment of cancer. Procedures MK-2206 was tested against the PPTP in vitro panel using a 96-hour exposure (1.0?nM10?mu M), and in vivo using thrice weekly dosing for a planned 4 weeks at its maximum tolerated dose (MTD) of 180?mg/kg. Results In vitro, the median relative IC50 value for MK-2206 was 2.2?mu M. Four cell lines with IC50 values?200?nM included two ALL cell lines (COG-LL-317 and RS4;11), an AML cell line with an activating KIT mutation (Kasumi-1), and a Ewing sarcoma cell line (CHLA-10). In vivo, MK-2206 induced significant differences in EFS distribution compared to control in 12 of 29 (41%) of the evaluable solid tumor xenografts and in 2 of 8 (25%) of the evaluable ALL xenografts. Significant differences in EFS distribution were most frequently noted in the osteosarcoma panel (6 of 6). A single solid tumor xenograft (OS-31) had a greater than twofold increase in time to event compared to control animals, with all other solid tumor xenografts showing lesser degrees of tumor growth inhibition. Objective responses were not observed for either the solid tumor or ALL xenografts. Conclusions MK-2206 showed its most consistent activity in vitro against ALL cell lines and in vivo against osteosarcoma xenografts. However, no objective responses were observed in solid tumor or ALL xenografts. Further preclinical work evaluating MK-2206 in pediatric models in the combination therapy setting may contribute to its pediatric development. Pediatr Blood Cancer 2012;59:518524. (c) 2011 Wiley Periodicals, Inc.
C1 [Gorlick, Richard] Childrens Hosp Montefiore, Bronx, NY USA.
[Maris, John M.] Univ Penn, Childrens Hosp Philadelphia, Sch Med, Abramson Family Canc Res Inst, Philadelphia, PA 19104 USA.
[Houghton, Peter J.; Kurmasheva, Raushan T.] Nationwide Childrens Hosp, Columbus, OH USA.
[Lock, Richard; Carol, Hernan] Childrens Canc Inst Australia Med Res, Randwick, NSW, Australia.
[Kolb, E. Anders] Alfred I DuPont Hosp Children, Wilmington, DE USA.
[Keir, Stephen T.] Duke Univ, Med Ctr, Durham, NC USA.
[Reynolds, C. Patrick; Kang, Min H.] Texas Tech Univ, Hlth Sci Ctr, Lubbock, TX 79430 USA.
[Billups, Catherine A.] St Jude Childrens Hosp, Memphis, TN 38105 USA.
[Smith, Malcolm A.] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA.
RP Gorlick, R (reprint author), Montefiore Med Ctr, Dept Pediat, 3415 Bainbridge Ave, Bronx, NY 10467 USA.
EM rgorlick@montefiore.org
RI Houghton, Peter/E-3265-2011; Carol, Hernan/F-5750-2013; Lock,
Richard/G-4253-2013;
OI Carol, Hernan/0000-0002-9443-8032; Reynolds, C.
Patrick/0000-0002-2827-8536
FU National Cancer Institute [NO1-CM-42216, CA21765, CA108786]
FX Grant sponsor: National Cancer Institute; Grant numbers: NO1-CM-42216,
CA21765, CA108786.
NR 39
TC 13
Z9 14
U1 2
U2 9
PU WILEY PERIODICALS, INC
PI SAN FRANCISCO
PA ONE MONTGOMERY ST, SUITE 1200, SAN FRANCISCO, CA 94104 USA
SN 1545-5009
J9 PEDIATR BLOOD CANCER
JI Pediatr. Blood Cancer
PD SEP
PY 2012
VL 59
IS 3
BP 518
EP 524
DI 10.1002/pbc.23412
PG 7
WC Oncology; Hematology; Pediatrics
SC Oncology; Hematology; Pediatrics
GA 972XJ
UT WOS:000306314400018
PM 22102563
ER
PT J
AU Keir, ST
Morton, CL
Wu, JR
Kurmasheva, RT
Houghton, PJ
Smith, MA
AF Keir, Stephen T.
Morton, Christopher L.
Wu, Jianrong
Kurmasheva, Raushan T.
Houghton, Peter J.
Smith, Malcolm A.
TI Initial testing of the multitargeted kinase inhibitor pazopanib by the
pediatric preclinical testing program
SO PEDIATRIC BLOOD & CANCER
LA English
DT Article
DE developmental therapeutics; pazopanib; preclinical testing
ID MULTIKINASE ANGIOGENESIS INHIBITOR; ENDOTHELIAL GROWTH-FACTOR;
RENAL-CELL CARCINOMA; PHASE-II; RECURRENT; THERAPY; CANCER; TRIAL
AB Pazopanib is an oral angiogenesis inhibitor targeting vascular growth factor receptor-1, -2, and -3, platelet derived growth factor receptor-a, platelet derived growth factor receptor-beta, and KIT that has demonstrated activity against a variety of adult cancer xenografts. Pazopanib was tested against a panel of pediatric rhabdomyosarcoma and Ewing sarcoma xenografts at a dose of 108?mg/kg/day or 100?mg/kg twice daily, administered orally for 28 days. While no objective responses were observed, pazopanib induced statistically significant differences in event-free survival compared to controls in approximately one-half of the sarcoma xenograft models tested. Though well tolerated, pazopanib showed limited activity against the sarcoma models evaluated, with the best tumor responses being growth delay. Pediatr Blood Cancer 2012;59:586588. (c) 2011 Wiley Periodicals, Inc.
C1 [Keir, Stephen T.] Duke Univ, Med Ctr, Durham, NC USA.
[Morton, Christopher L.; Wu, Jianrong] St Jude Childrens Hosp, Memphis, TN 38105 USA.
[Kurmasheva, Raushan T.; Houghton, Peter J.] Nationwide Childrens Hosp, Columbus, OH USA.
[Smith, Malcolm A.] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA.
RP Keir, ST (reprint author), Preston Robert Tisch Brain Tumor Ctr Duke, Dept Surg, Durham, NC USA.
EM keir0001@mc.duke.edu
RI Houghton, Peter/E-3265-2011
FU National Cancer Institute [NO1-CM-42216, CA21765, CA108786]
FX Grant sponsor: National Cancer Institute; Grant numbers: NO1-CM-42216,
CA21765, CA108786.
NR 18
TC 14
Z9 14
U1 0
U2 2
PU WILEY PERIODICALS, INC
PI SAN FRANCISCO
PA ONE MONTGOMERY ST, SUITE 1200, SAN FRANCISCO, CA 94104 USA
SN 1545-5009
J9 PEDIATR BLOOD CANCER
JI Pediatr. Blood Cancer
PD SEP
PY 2012
VL 59
IS 3
BP 586
EP 588
DI 10.1002/pbc.24016
PG 3
WC Oncology; Hematology; Pediatrics
SC Oncology; Hematology; Pediatrics
GA 972XJ
UT WOS:000306314400034
PM 22190407
ER
PT J
AU Umehara, D
Kawamura, M
Odahara, Y
Watanabe, S
Hanson, C
Ruscetti, S
Nishigaki, K
AF Umehara, Daigo
Kawamura, Maki
Odahara, Yuka
Watanabe, Shinya
Hanson, Charlotte
Ruscetti, Sandra
Nishigaki, Kazuo
TI Role of N-terminal sequences of the tyrosine kinase sf-Stk in
transformation of rodent fibroblasts by variants of Friend spleen
focus-forming virus
SO INTERNATIONAL JOURNAL OF CANCER
LA English
DT Article
DE retrovirus; sf-Stk; transformation; env; pathogenesis; erythroleukemia;
tyrosine kinase
ID COMPLETE NUCLEOTIDE-SEQUENCE; TRUNCATED FORM; PHOSPHATIDYLINOSITOL
3-KINASE; CONSTITUTIVE ACTIVATION; ERYTHROPOIETIN RECEPTOR; ENVELOPE
GLYCOPROTEIN; INDEPENDENT GROWTH; LEUKEMIA VIRUS; DNA-BINDING; CELLS
AB Infection of erythroid cells by Friend spleen focus-forming virus (SFFV) leads to acute erythroid hyperplasia in mice, due to expression of its unique envelope glycoprotein, gp55. Erythroid cells expressing SFFV gp55 proliferate in the absence of their normal regulator, erythropoietin, because of the interaction among the viral envelope protein, the erythropoietin receptor, and a short form of the receptor tyrosine kinase Stk (sf-Stk). This leads to constitutive activation of several signal transduction pathways. Our previous studies showed that sf-Stk interacts with SFFV gp55, forming disulfide-linked complexes. This covalent interaction, along with other noncovalent interactions with SFFV-gp55, results in constitutive tyrosine phosphorylation of sf-Stk and rodent fibroblast transformation. Here, we determined the precise amino acid region within sf-Stk that contributes to fibroblast transformation by the polycythemia-inducing (SFFV-P) and the anemia-inducing (SFFV-A) strains of SFFV. Sf-Stk deletion mutants showed different transforming abilities in fibroblasts infected with SFFV-P and SFFV-A, although the N-terminal extracellular domain of sf-Stk was essential for fibroblast transformation by both viruses. Point mutations of sf-Stk indicated that cysteine 19 was critical for fibroblast transformation by SFFV-P, although all four cysteines (8, 19, 37 and 42) appeared to be important for fibroblast transformation by both SFFV-P and SFFV-A. Mutation of sf-Stk cysteine 19 abolished its ability to form dimers with SFFV-P and SFFV-A gp55. These results suggest that the interaction between sf-Stk and the envelope proteins of the polycythemia- and anemia-inducing variants of SFFV is architecturally different.
C1 [Umehara, Daigo; Kawamura, Maki; Odahara, Yuka; Watanabe, Shinya; Nishigaki, Kazuo] Yamaguchi Univ, Dept Vet Med, Lab Mol Immunol & Infect Dis, Yamaguchi 7538515, Japan.
[Hanson, Charlotte; Ruscetti, Sandra] Natl Canc Inst Frederick, Lab Canc Prevent, Frederick, MD USA.
RP Nishigaki, K (reprint author), Yamaguchi Univ, Dept Vet Med, Lab Mol Immunol & Infect Dis, 1677-1 Yoshida, Yamaguchi 7538515, Japan.
EM kaz@yamaguchi-u.ac.jp
FU Ministry of Education, Science, Sports, and Culture of Japan
FX Grant sponsor: Ministry of Education, Science, Sports, and Culture of
Japan
NR 36
TC 0
Z9 0
U1 0
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0020-7136
J9 INT J CANCER
JI Int. J. Cancer
PD SEP 1
PY 2012
VL 131
IS 5
BP 1083
EP 1094
DI 10.1002/ijc.27330
PG 12
WC Oncology
SC Oncology
GA 965GZ
UT WOS:000305756900035
PM 22034044
ER
PT J
AU Pesch, B
Kendzia, B
Gustavsson, P
Jockel, KH
Johnen, G
Pohlabeln, H
Olsson, A
Ahrens, W
Gross, IM
Brunske, I
Wichmann, HE
Merletti, F
Richiardi, L
Simonato, L
Fortes, C
Siemiatycki, J
Parent, ME
Consonni, D
Landi, MT
Caporaso, N
Zaridze, D
Cassidy, A
Szeszenia-Dabrowska, N
Rudnai, P
Lissowska, J
Stucker, I
Fabianova, E
Dumitru, RS
Bencko, V
Foretova, L
Janout, V
Rudin, CM
Brennan, P
Boffetta, P
Straif, K
Bruning, T
AF Pesch, Beate
Kendzia, Benjamin
Gustavsson, Per
Joeckel, Karl-Heinz
Johnen, Georg
Pohlabeln, Hermann
Olsson, Ann
Ahrens, Wolfgang
Gross, Isabelle Mercedes
Brueske, Irene
Wichmann, Heinz-Erich
Merletti, Franco
Richiardi, Lorenzo
Simonato, Lorenzo
Fortes, Cristina
Siemiatycki, Jack
Parent, Marie-Elise
Consonni, Dario
Landi, Maria Teresa
Caporaso, Neil
Zaridze, David
Cassidy, Adrian
Szeszenia-Dabrowska, Neonila
Rudnai, Peter
Lissowska, Jolanta
Stuecker, Isabelle
Fabianova, Eleonora
Dumitru, Rodica Stanescu
Bencko, Vladimir
Foretova, Lenka
Janout, Vladimir
Rudin, Charles M.
Brennan, Paul
Boffetta, Paolo
Straif, Kurt
Bruening, Thomas
TI Cigarette smoking and lung cancerurelative risk estimates for the major
histological types from a pooled analysis of case-control studies
SO INTERNATIONAL JOURNAL OF CANCER
LA English
DT Article
DE cigarette smoking; lung cancer; relative risk characterization; tobacco
smoke; stem cells
ID STEM-CELLS; BRONCHIOLOALVEOLAR CARCINOMA; PROSPECTIVE COHORT; CANCER
MORTALITY; PROGENITOR CELLS; BLADDER-CANCER; NEVER-SMOKERS;
UNITED-STATES; ADENOCARCINOMA; EPIDEMIOLOGY
AB Lung cancer is mainly caused by smoking, but the quantitative relations between smoking and histologic subtypes of lung cancer remain inconclusive. By using one of the largest lung cancer datasets ever assembled, we explored the impact of smoking on risks of the major cell types of lung cancer. This pooled analysis included 13,169 cases and 16,010 controls from Europe and Canada. Studies with population controls comprised 66.5% of the subjects. Adenocarcinoma (AdCa) was the most prevalent subtype in never smokers and in women. Squamous cell carcinoma (SqCC) predominated in male smokers. Age-adjusted odds ratios (ORs) were estimated with logistic regression. ORs were elevated for all metrics of exposure to cigarette smoke and were higher for SqCC and small cell lung cancer (SCLC) than for AdCa. Current male smokers with an average daily dose of >30 cigarettes had ORs of 103.5 (95% confidence interval (CI): 74.8143.2) for SqCC, 111.3 (95% CI: 69.8177.5) for SCLC and 21.9 (95% CI: 16.629.0) for AdCa. In women, the corresponding ORs were 62.7 (95% CI: 31.5124.6), 108.6 (95% CI: 50.7232.8) and 16.8 (95% CI: 9.230.6), respectively. Although ORs started to decline soon after quitting, they did not fully return to the baseline risk of never smokers even 35 years after cessation. The major result that smoking exerted a steeper risk gradient on SqCC and SCLC than on AdCa is in line with previous population data and biological understanding of lung cancer development.
C1 [Pesch, Beate; Kendzia, Benjamin; Johnen, Georg; Gross, Isabelle Mercedes; Bruening, Thomas] Inst Ruhr Univ Bochum IPA, Inst Prevent & Occupat Med, German Social Accid Insurance, Bochum, Germany.
[Gustavsson, Per; Olsson, Ann] Karolinska Inst, Inst Environm Med, S-10401 Stockholm, Sweden.
[Joeckel, Karl-Heinz] Univ Hosp Essen, Inst Med Informat Biometry & Epidemiol, Essen, Germany.
[Pohlabeln, Hermann; Ahrens, Wolfgang] Univ Bremen, Bremen Inst Prevent Res & Social Med, D-28359 Bremen, Germany.
[Olsson, Ann; Brennan, Paul; Straif, Kurt] Int Agcy Res Canc, F-69372 Lyon, France.
[Brueske, Irene; Wichmann, Heinz-Erich] HelmholtzZentrum Munchen, Inst Epidemiol, Munich, Germany.
[Merletti, Franco; Richiardi, Lorenzo] Univ Turin, Canc Epidemiol Unit, Turin, Italy.
[Merletti, Franco; Richiardi, Lorenzo] Univ Turin, CPO Piemonte, Turin, Italy.
[Richiardi, Lorenzo] Univ Padua, Dept Environm Med & Publ Hlth, Padua, Italy.
[Fortes, Cristina] IDI IRCCS, Clin Epidemiol Unit, Rome, Italy.
[Siemiatycki, Jack; Parent, Marie-Elise] Univ Montreal Hosp Res Ctr CRCHUM, Montreal, PQ, Canada.
[Siemiatycki, Jack; Parent, Marie-Elise] Sch Publ Hlth, Montreal, PQ, Canada.
[Parent, Marie-Elise] Univ Quebec, Inst Armand Frappier, INRS, Laval, PQ, Canada.
[Consonni, Dario] Osped Maggiore Policlin, Fdn IRCCS Ca Granda, Epidemiol Unit, Milan, Italy.
[Landi, Maria Teresa; Caporaso, Neil] Natl Canc Inst, Div Canc Epidemiol & Genet, Bethesda, MD USA.
[Zaridze, David] Russian Canc Res Ctr, Inst Carcinogenesis, Moscow, Russia.
[Cassidy, Adrian] Univ Liverpool, Canc Res Ctr, Roy Castle Lung Canc Res Programme, Liverpool L69 3BX, Merseyside, England.
[Szeszenia-Dabrowska, Neonila] Nofer Inst Occupat Med, Lodz, Poland.
[Rudnai, Peter] Natl Inst Environm Hlth, Budapest, Hungary.
[Lissowska, Jolanta] Inst Oncol, Warsaw, Poland.
[Lissowska, Jolanta] M Sklodowska Curie Canc Ctr, Warsaw, Poland.
[Stuecker, Isabelle] INSERM, U 754 IFR69, Villejuif, France.
[Fabianova, Eleonora] Reg Author Publ Hlth, Specialized State Hlth Inst, Dept Occupat Hlth, Banska Bystrica, Slovakia.
[Dumitru, Rodica Stanescu] Natl Inst Publ Hlth, Bucharest, Romania.
[Bencko, Vladimir] Charles Univ Prague, Fac Med 1, Inst Hyg & Epidemiol, Prague, Czech Republic.
[Foretova, Lenka] Masaryk Mem Canc Inst, Brno, Czech Republic.
[Janout, Vladimir] Palacky Univ, Dept Prevent Med, Fac Med, CR-77147 Olomouc, Czech Republic.
[Rudin, Charles M.] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD USA.
[Boffetta, Paolo] Mt Sinai Hosp, Mt Sinai Sch Med, Tisch Canc Inst, New York, NY 10029 USA.
[Boffetta, Paolo] Int Prevent Res Inst, Lyon, France.
RP Pesch, B (reprint author), Inst Ruhr Univ Bochum IPA, Inst Prevent & Occupat Med, German Social Accid Insurance, Burkle de la Camp Pl 1, Bochum, Germany.
EM pesch@ipa-dguv.de
RI Zaridze, David/K-5605-2013; Bruske, Irene/N-3125-2013; Janout,
Vladimir/M-5133-2014; Szeszenia-Dabrowska, Neonila/F-7190-2010; Bruning,
Thomas/G-8120-2015; Consonni, Dario/K-7943-2016
OI Bruning, Thomas/0000-0001-9560-5464; Consonni, Dario/0000-0002-8935-3843
FU German Social Accident Insurance [FP 271]; Canadian Institutes of Health
Research; Guzzo-SRC Chair in Environment and Cancer; Fondation de
France; German Federal Ministry of Education, Science, Research, and
Technology; Ministry of Labour and Social Affairs; EC's INCO-COPERNICUS
Program; Polish State Committee for Science Research; Roy Castle
Foundation; NIH/NCI/DCEG; Lombardy Region; INAIL; European Union;
Italian Association for Cancer Research; Region Piedmont; Compagnia di
San Paolo; Europe Against Cancer Program; Swedish Council for Work Life
Research; Swedish EPA
FX Grant sponsor: German Social Accident Insurance; Grant number: FP 271;
Grant sponsors: Canadian Institutes of Health Research and Guzzo-SRC
Chair in Environment and Cancer, the Fondation de France, the German
Federal Ministry of Education, Science, Research, and Technology and the
Ministry of Labour and Social Affairs, EC's INCO-COPERNICUS Program,
Polish State Committee for Science Research, Roy Castle Foundation,
NIH/NCI/DCEG Intramural Research Program, Lombardy Region, INAIL and the
European Union Nuclear Fission Safety Program, Italian Association for
Cancer Research, Region Piedmont, Compagnia di San Paolo, Europe Against
Cancer Program, the Swedish Council for Work Life Research and the
Swedish EPA
NR 46
TC 91
Z9 92
U1 1
U2 11
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0020-7136
J9 INT J CANCER
JI Int. J. Cancer
PD SEP 1
PY 2012
VL 131
IS 5
BP 1210
EP 1219
DI 10.1002/ijc.27339
PG 10
WC Oncology
SC Oncology
GA 965GZ
UT WOS:000305756900049
PM 22052329
ER
PT J
AU Cardwell, CR
Abnet, CC
Veal, P
Hughes, CM
Cantwell, MM
Murray, LJ
AF Cardwell, Chris R.
Abnet, Christian C.
Veal, Philip
Hughes, Carmel M.
Cantwell, Marie M.
Murray, Liam J.
TI Exposure to oral bisphosphonates and risk of cancer
SO INTERNATIONAL JOURNAL OF CANCER
LA English
DT Article
DE cancer; risk; bisphosphonates; cohort; epidemiology
ID ADJUVANT CLODRONATE TREATMENT; VITAMIN-D SUPPLEMENTATION; BONE-MINERAL
DENSITY; BREAST-CANCER; POSTMENOPAUSAL WOMEN; ZOLEDRONIC ACID;
FOLLOW-UP; COLORECTAL-CANCER; SUBSEQUENT RISK; COLON-CANCER
AB Recently, oral bisphosphonate use has increased markedly in the United States and elsewhere. Little is known about cancer risks associated with these drugs. A few studies have observed associations between bisphosphonates and the risk of breast, colorectal and esophageal cancer. However, the risk of all cancer and the risk of other cancers have not been investigated. In our study, we examined the risk of all cancer and site specific cancers in individuals taking bisphosphonates. Data were extracted from the UK General Practice Research Database to compare site-specific cancer incidence in a cohort of oral bisphosphonate users and a control cohort. Hazard ratios (HRs) were calculated using Cox regression modeling. The bisphosphonate and control cohort contained 41,826 participants (mean age 70, 81% female). Overall, the bisphosphonate cohort compared with the control cohort had a reduced risk of all cancer after any bisphosphonate usage [HR = 0.87, 95% confidence interval (CI) 0.82, 0.92]. In the bisphosphonate cohort, compared with the control cohort, there was no evidence of a difference in the risk of lung (HR = 1.03, 95% CI 0.88, 1.20) or prostate cancer (HR = 0.86, 95% CI 0.67, 1.09) but breast (HR = 0.71, 95% CI 0.62, 0.81) and colorectal cancer (HR = 0.74, 95% CI, 0.600.91) were both reduced. Our findings indicate that bisphosphonates do not appear to increase cancer risk. Although reductions in breast and colorectal cancer incidence were observed in bisphosphonate users it is unclear, particularly for breast cancer, to what extent confounding by low bone density may explain the association.
C1 [Cardwell, Chris R.; Veal, Philip; Cantwell, Marie M.; Murray, Liam J.] Queens Univ Belfast, Ctr Publ Hlth, Sch Med Dent & Biomed Sci, Belfast BT12 6BJ, Antrim, North Ireland.
[Abnet, Christian C.] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD USA.
[Hughes, Carmel M.] Queens Univ Belfast, Sch Pharm, Belfast BT12 6BJ, Antrim, North Ireland.
RP Cardwell, CR (reprint author), Queens Univ Belfast, Ctr Publ Hlth, Sch Med Dent & Biomed Sci, Grosvenor Rd, Belfast BT12 6BJ, Antrim, North Ireland.
EM c.cardwell@qub.ac.uk
RI Research Datalink, Clinical Practice/H-2477-2013; Abnet,
Christian/C-4111-2015; CPRD, CPRD/B-9594-2017;
OI Abnet, Christian/0000-0002-3008-7843; Cardwell,
Chris/0000-0002-2689-4335
FU Medical Research Council; MHRA; UK Medicines and Healthcare Products
Regulatory Agency
FX Grant sponsor: Medical Research Council's License Agreement with MHRA;
We thank Maciej Domanski, MSc (Centre for Public Health, Queen's
University Belfast, Belfast, United Kingdom) for data management. This
study is based in part on data from the Full Feature General Practice
Research Database obtained under license from the UK Medicines and
Healthcare Products Regulatory Agency. Access to the GPRD database was
funded through the Medical Research Council's license agreement with the
UK Medicines and Healthcare Products Regulatory Agency. However, the
interpretation and conclusions contained in this study are those of the
authors alone.
NR 35
TC 26
Z9 26
U1 0
U2 5
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0020-7136
J9 INT J CANCER
JI Int. J. Cancer
PD SEP 1
PY 2012
VL 131
IS 5
BP E717
EP E725
DI 10.1002/ijc.27389
PG 9
WC Oncology
SC Oncology
GA 965GZ
UT WOS:000305756900013
PM 22161552
ER
PT J
AU Sun, HM
Xia, MH
Austin, CP
Huang, RL
AF Sun, Hongmao
Xia, Menghang
Austin, Christopher P.
Huang, Ruili
TI Paradigm Shift in Toxicity Testing and Modeling
SO AAPS JOURNAL
LA English
DT Review
DE computational toxicology; qHTS; risk assessment; Tox21
ID NATIONAL-TOXICOLOGY-PROGRAM; RODENT CARCINOGENICITY BIOASSAYS;
THROUGHPUT SCREENING DATA; SUPPORT VECTOR MACHINE; COMPUTATIONAL
TOXICOLOGY; PREDICTIVE-TOXICOLOGY; DRUG DISCOVERY; ANIMAL-MODELS;
IMMUNOTOXICITY ASSESSMENT; ENVIRONMENTAL CHEMICALS
AB The limitations of traditional toxicity testing characterized by high-cost animal models with low-throughput readouts, inconsistent responses, ethical issues, and extrapolability to humans call for alternative strategies for chemical risk assessment. A new strategy using in vitro human cell-based assays has been designed to identify key toxicity pathways and molecular mechanisms leading to the prediction of an in vivo response. The emergence of quantitative high-throughput screening (qHTS) technology has proved to be an efficient way to decompose complex toxicological end points to specific pathways of targeted organs. In addition, qHTS has made a significant impact on computational toxicology in two aspects. First, the ease of mechanism of action identification brought about by in vitro assays has enhanced the simplicity and effectiveness of machine learning, and second, the high-throughput nature and high reproducibility of qHTS have greatly improved the data quality and increased the quantity of training datasets available for predictive model construction. In this review, the benefits of qHTS routinely used in the US Tox21 program will be highlighted. Quantitative structure-activity relationships models built on traditional in vivo data and new qHTS data will be compared and analyzed. In conjunction with the transition from the pilot phase to the production phase of the Tox21 program, more qHTS data will be made available that will enrich the data pool for predictive toxicology. It is perceivable that new in silico toxicity models based on high-quality qHTS data will achieve unprecedented reliability and robustness, thus becoming a valuable tool for risk assessment and drug discovery.
C1 [Sun, Hongmao; Xia, Menghang; Austin, Christopher P.; Huang, Ruili] NIH, Dept Hlth & Human Serv, Chem Genom Ctr, Bethesda, MD 20892 USA.
RP Sun, HM (reprint author), NIH, Dept Hlth & Human Serv, Chem Genom Ctr, 9800 Med Ctr Dr, Bethesda, MD 20892 USA.
EM hongmao.sun@nih.gov; huangru@mail.nih.gov
FU Intramural Research Programs of the National Toxicology Program
[Y2-ES-7020-01]; National Institute of Environmental Health Sciences
(NIEHS); National Center for Advancing Translational Sciences (NCATS),
National Institutes of Health (NIH)
FX This work was supported by the Intramural Research Programs (Interagency
agreement #Y2-ES-7020-01) of the National Toxicology Program, National
Institute of Environmental Health Sciences (NIEHS), and the National
Center for Advancing Translational Sciences (NCATS), National Institutes
of Health (NIH). The statements, opinions, or conclusions contained
therein do not necessarily represent the statements, opinions, or
conclusions of NIEHS, or NCATS, NIH, or the US government. We thank in
particular Anna Rossoshek for helpful comments and suggestions during
the preparation of this manuscript.
NR 97
TC 26
Z9 26
U1 1
U2 31
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1550-7416
J9 AAPS J
JI AAPS J.
PD SEP
PY 2012
VL 14
IS 3
BP 473
EP 480
DI 10.1208/s12248-012-9358-1
PG 8
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 962DO
UT WOS:000305519900012
PM 22528508
ER
PT J
AU Fleg, JL
Strait, J
AF Fleg, Jerome L.
Strait, James
TI Age-associated changes in cardiovascular structure and function: a
fertile milieu for future disease
SO HEART FAILURE REVIEWS
LA English
DT Article
DE Cardiovascular; Aging; Arterial; Ventricular function; Exercise; beta
adrenergic
ID SUBCLINICAL ARTERIAL-DISEASE; HEALTHY-MEN; HUMAN HEART;
ECHOCARDIOGRAPHIC-ASSESSMENT; DIASTOLIC DYSFUNCTION; CONTRACTION
DURATION; MYOCARDIAL-ISCHEMIA; AEROBIC CAPACITY; DYNAMIC EXERCISE; CYCLE
EXERCISE
AB Important changes occur in the cardiovascular system with advancing age, even in apparently healthy individuals. Thickening and stiffening of the large arteries develop due to collagen and calcium deposition and loss of elastic fibers in the medial layer. These arterial changes cause systolic blood pressure to rise with age, while diastolic blood pressure generally declines after the sixth decade. In the left ventricle, modest concentric wall thickening occurs due to cellular hypertrophy, but cavity size does not change. Although left ventricular systolic function is preserved across the age span, early diastolic filling rate declines 30-50% between the third and ninth decades. Conversely, an age-associated increase in late diastolic filling due to atrial contraction preserves end-diastolic volume. Aerobic exercise capacity declines approximately 10% per decade in cross-sectional studies; in longitudinal studies, however, this decline is accelerated in the elderly. Reductions in peak heart rate and peripheral oxygen utilization but not stroke volume appear to mediate the age-associated decline in aerobic capacity. Deficits in both cardiac beta-adrenergic receptor density and in the efficiency of postsynaptic beta-adrenergic signaling contribute significantly to the reduced cardiovascular performance during exercise in older adults. Although these cardiovascular aging changes are considered "normative", they lower the threshold for the development of cardiovascular disease, which affects the majority of older adults.
C1 [Fleg, Jerome L.] NHLBI, Div Cardiovasc Sci, Bethesda, MD 20892 USA.
[Strait, James] NIA, Cardiovasc Sci Lab, Baltimore, MD 21224 USA.
RP Fleg, JL (reprint author), NHLBI, Div Cardiovasc Sci, 6701 Rockledge Dr,Room 8150, Bethesda, MD 20892 USA.
EM flegj@nhlbi.nih.gov; strait.j@nia.nih.gov
FU Intramural NIH HHS [Z99 HL999999]
NR 51
TC 31
Z9 34
U1 0
U2 7
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 1382-4147
J9 HEART FAIL REV
JI Heart Fail. Rev.
PD SEP
PY 2012
VL 17
IS 4-5
SI SI
BP 545
EP 554
DI 10.1007/s10741-011-9270-2
PG 10
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 957AC
UT WOS:000305129800003
PM 21809160
ER
PT J
AU Jacobson, KA
Balasubramanian, R
Deflorian, F
Gao, ZG
AF Jacobson, Kenneth A.
Balasubramanian, Ramachandran
Deflorian, Francesca
Gao, Zhan-Guo
TI G protein-coupled adenosine (P1) and P2Y receptors: ligand design and
receptor interactions
SO PURINERGIC SIGNALLING
LA English
DT Article
DE GPCR structure; Adenosine receptors; P2Y receptors; Agonists;
Antagonists; Clinical trials, nucleosides; Nucleotides
ID SITE-DIRECTED MUTAGENESIS; AMINO-ACID-RESIDUES; HUMAN MAST-CELLS; A(2B)
ADENOSINE; NUCLEOTIDE RECEPTORS; MUTATIONAL ANALYSIS; THERAPEUTIC
APPLICATIONS; ANTAGONIST RECOGNITION; MOLECULAR RECOGNITION;
PHYLOGENETIC ANALYSIS
AB The medicinal chemistry and pharmacology of the four subtypes of adenosine receptors (ARs) and the eight subtypes of P2Y receptors (P2YRs, activated by a range of purine and pyrimidine mono- and dinucleotides) has recently advanced significantly leading to selective ligands. X-ray crystallographic structures of both agonist- and antagonist-bound forms of the A(2A)AR have provided unprecedented three-dimensional detail concerning molecular recognition in the binding site and the conformational changes in receptor activation. It is apparent that this ubiquitous cell signaling system has implications for understanding and treating many diseases. ATP and other nucleotides are readily released from intracellular sources under conditions of injury and organ stress, such as hypoxia, ischemia, or mechanical stress, and through channels and vesicular release. Adenosine may be generated extracellularly or by cellular release. Therefore, depending on pathophysiological factors, in a given tissue, there is often a tonic activation of one or more of the ARs or P2YRs that can be modulated by exogenous agents for a beneficial effect. Thus, this field has provided fertile ground for pharmaceutical development, leading to clinical trials of selective receptor ligands as imaging agents or for conditions including cardiac arrhythmias, ischemia/reperfusion injury, diabetes, pain, thrombosis, Parkinson's disease, rheumatoid arthritis, psoriasis, dry eye disease, pulmonary diseases such as cystic fibrosis, glaucoma, cancer, chronic hepatitis C, and other diseases.
C1 [Jacobson, Kenneth A.] NIDDKD, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA.
RP Jacobson, KA (reprint author), NIDDKD, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bldg 8A,Rm B1A-19, Bethesda, MD 20892 USA.
EM kajacobs@helix.nih.gov
RI Jacobson, Kenneth/A-1530-2009
OI Jacobson, Kenneth/0000-0001-8104-1493
FU NIDDK, National Institutes of Health
FX Supported by the NIDDK Intramural Research Program, National Institutes
of Health.
NR 119
TC 33
Z9 34
U1 1
U2 21
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 1573-9538
EI 1573-9546
J9 PURINERG SIGNAL
JI Purinergic Signal.
PD SEP
PY 2012
VL 8
IS 3
SI SI
BP 419
EP 436
DI 10.1007/s11302-012-9294-7
PG 18
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA 949QO
UT WOS:000304591000005
PM 22371149
ER
PT J
AU Goldberg, RN
Lang, BE
Coxon, B
Decker, SR
AF Goldberg, Robert N.
Lang, Brian E.
Coxon, Bruce
Decker, Stephen R.
TI Saturation molalities and standard molar enthalpies of solution of
alpha-D-xylose(cr) in H2O(l); standard molar enthalpies of solution of
1,4-beta-D-xylobiose(am), and 1,4-beta-D-xylotriose(am) in H2O(l)
SO JOURNAL OF CHEMICAL THERMODYNAMICS
LA English
DT Article
DE Enthalpy of solution; Saturation molality; Solubility; Standard
formation properties; 1,4-beta-D-Xylobiose; 1,4-beta-D-Xylotriose;
alpha-D-Xylose
ID AQUEOUS-SOLUTION; WATER; THERMODYNAMICS; HYDROLYSIS; SOLUBILITY;
PENTOSES; HEXOSES; POLYOLS; MALTOSE; XYLOSE
AB The saturation molality of alpha-D-xylose(cr) in water was measured by using HPLC and is m(sat) = (8.43 +/- 0.42) mol . kg(-1) at T = 298.15 K. It was also established that the anhydrous form of alpha-D-xylose(cr) is the crystalline form that is in equilibrium with the aqueous solution at T = 298.15 K. Solution calorimetry was used to measure the following standard molar enthalpies of solution at T = 298.15 K: Delta H-sol(m)degrees = (12.10 +/- 0.12) kJ . mol(-1) for alpha-D-xylose(cr); Delta H-sol(m)degrees = -(8.1 +/- 2.7) kJ . mol(-1) for 1,4-beta-D-xylobiose(am); and Delta H-sol(m)degrees = -(24.1 +/- 6.4) kJ . mol(-1) for 1,4-beta-D-xylotriose(am). It was observed that both 1,4-beta-D-xylobiose(am) and 1,4-beta-D-xylotriose(am) were amorphous substances and that they form thick gels in water in which no solid phase is present. Consequently, it is not possible to measure m(sat) for these two substances. All substances were carefully characterized by using both HPLC and Karl Fischer analysis. NMR was used to measure the anomeric purity of the alpha-D-xylose(cr). Thermodynamic network calculations were used to calculate standard molar formation properties for the aforementioned substances. (C) 2011 Elsevier Ltd. All rights reserved.
C1 [Goldberg, Robert N.; Lang, Brian E.] Natl Inst Stand & Technol, Div Biochem Sci, Gaithersburg, MD 20876 USA.
[Goldberg, Robert N.] Univ Maryland Baltimore Cty, Dept Chem & Biochem, Baltimore, MD 21250 USA.
[Coxon, Bruce] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD 20892 USA.
[Decker, Stephen R.] Natl Renewable Energy Lab, Biosci Ctr, Golden, CO 80401 USA.
RP Goldberg, RN (reprint author), Natl Inst Stand & Technol, Div Biochem Sci, Gaithersburg, MD 20876 USA.
EM robert.goldberg@nist.gov; brian.lang@nist.gov; coxonb@mail.nih.gov;
steve.decker@nrel.gov
FU Department of Energy Office of the Biomass Program; US Department of
Energy [DE-AC36-08-GO28308]; National Renewable Energy Laboratory
FX We thank Dr. Alan Mighell for his literature search on possible
crystalline forms of 1,4-beta-D-xylobiose and 1,4-beta-D-xylotriose.
This work was funded, in part, by the Department of Energy Office of the
Biomass Program and by the US Department of Energy under Contract No.
DE-AC36-08-GO28308 with the National Renewable Energy Laboratory.
NR 32
TC 6
Z9 6
U1 1
U2 7
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0021-9614
J9 J CHEM THERMODYN
JI J. Chem. Thermodyn.
PD SEP
PY 2012
VL 52
BP 2
EP 10
DI 10.1016/j.jct.2011.07.004
PG 9
WC Thermodynamics; Chemistry, Physical
SC Thermodynamics; Chemistry
GA 942OZ
UT WOS:000304056300002
ER
PT J
AU Coussens, NP
Schuck, P
Zhao, HY
AF Coussens, Nathan P.
Schuck, Peter
Zhao, Huaying
TI Strategies for assessing proton linkage to bimolecular interactions by
global analysis of isothermal titration calorimetry data
SO JOURNAL OF CHEMICAL THERMODYNAMICS
LA English
DT Article
DE Protein interactions; Thermodynamics; Proton linkage; Isothermal
titration calorimetry; Global analysis; SEDPHAT
ID ASPARTIC PROTEASE; DRUG DISCOVERY; LEAST-SQUARES; BINDING; ENERGETICS;
COMPLEXES; DOMAIN; SITE; THERMODYNAMICS; COOPERATIVITY
AB Isothermal titration calorimetry (ITC) is a traditional and powerful method for studying the linkage of ligand binding to proton uptake or release. The theoretical framework has been developed for more than two decades and numerous applications have appeared. In the current work, we explored strategic aspects of experimental design. To this end, we simulated families of ITC data sets that embed different strategies with regard to the number of experiments, range of experimental pH, buffer ionization enthalpy, and temperature. We then re-analyzed the families of data sets in the context of global analysis, employing a proton linkage binding model implemented in the global data analysis platform SEDPHAT, and examined the information content of all data sets by a detailed statistical error analysis of the parameter estimates. In particular, we studied the impact of different assumptions about the knowledge of the exact concentrations of the components, which in practice presents an experimental limitation for many systems. For example, the uncertainty in concentration may reflect imperfectly known extinction coefficients and stock concentrations or may account for different extents of partial inactivation when working with proteins at different pH values. Our results show that the global analysis can yield reliable estimates of the thermodynamic parameters for intrinsic binding and protonation, and that in the context of the global analysis the exact molecular component concentrations may not be required. Additionally, a comparison of data from different experimental strategies illustrates the benefit of conducting experiments at a range of temperatures. Published by Elsevier Ltd.
C1 [Schuck, Peter; Zhao, Huaying] Natl Inst Biomed Imaging & Bioengn, Dynam Macromol Assembly Sect, Lab Cellular Imaging & Macromol Biophys, NIH, Bethesda, MD 20892 USA.
[Coussens, Nathan P.] NCI, Lab Cellular & Mol Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Zhao, HY (reprint author), Natl Inst Biomed Imaging & Bioengn, Dynam Macromol Assembly Sect, Lab Cellular Imaging & Macromol Biophys, NIH, Bldg 13,Rm 3N17,13 S Dr, Bethesda, MD 20892 USA.
EM zhaoh3@mail.nih.gov
RI Zhao, Huaying/F-5716-2012;
OI Schuck, Peter/0000-0002-8859-6966
FU NCI; NIBIB, National Institutes of Health
FX We thank Dr. Lawrence E. Samelson for his encouragement and critical
reading of the manuscript. This work was supported by the Intramural
Research Programs of NCI and NIBIB, National Institutes of Health.
NR 43
TC 9
Z9 9
U1 1
U2 14
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0021-9614
J9 J CHEM THERMODYN
JI J. Chem. Thermodyn.
PD SEP
PY 2012
VL 52
BP 95
EP 107
DI 10.1016/j.jct.2012.02.008
PG 13
WC Thermodynamics; Chemistry, Physical
SC Thermodynamics; Chemistry
GA 942OZ
UT WOS:000304056300014
PM 22773848
ER
PT J
AU Kirschenbaum, LJ
Riesz, P
AF Kirschenbaum, Louis J.
Riesz, Peter
TI Sonochemical degradation of cyclic nitroxides in aqueous solution
SO ULTRASONICS SONOCHEMISTRY
LA English
DT Article
DE Nitroxides; Sonochemical decomposition; Hydrophobicity; EPR; Ultrasonics
ID SONOLYTIC DESTRUCTION; ORGANIC-COMPOUNDS; KINETICS MODEL; OH RADICALS;
REDUCTION; ANTIOXIDANTS; CAVITATION; ULTRASOUND; MECHANISM;
DECOMPOSITION
AB The sonochemical degradation of eight five- and six-membered nitroxides has been studied by EPR spectroscopy after exposure to ultrasound at a frequency of 354 kHz in argon-saturated aqueous solution. Concentration vs. time profiles do not follow a simple rate law. Octanol/water partition functions have been determined for all eight nitroxides, and an excellent linear correlation has been found between initial decomposition rates and hydrophobicity (log K-octanol/water). Variation of initial rate with concentration was investigated for one compound (TEMPONE) and is largely consistent with an equilibrium distribution of substrate between bulk solution and the gas/liquid interface. (C) 2012 Elsevier B.V. All rights reserved.
C1 [Kirschenbaum, Louis J.] Univ Rhode Isl, Dept Chem, Kingston, RI 02881 USA.
[Kirschenbaum, Louis J.; Riesz, Peter] NCI, Radiat Biol Branch, NIH, Bethesda, MD 20892 USA.
RP Kirschenbaum, LJ (reprint author), Univ Rhode Isl, Dept Chem, Kingston, RI 02881 USA.
EM Kirschenbaum@chm.uri.edu
NR 40
TC 5
Z9 5
U1 0
U2 11
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1350-4177
J9 ULTRASON SONOCHEM
JI Ultrason. Sonochem.
PD SEP
PY 2012
VL 19
IS 5
BP 1114
EP 1119
DI 10.1016/j.ultsonch.2012.01.014
PG 6
WC Acoustics; Chemistry, Multidisciplinary
SC Acoustics; Chemistry
GA 942VA
UT WOS:000304076900021
PM 22361491
ER
PT J
AU Liu, MM
Chan, CC
Tuo, JS
AF Liu, Melissa M.
Chan, Chi-Chao
Tuo, Jingsheng
TI Genetic mechanisms and age-related macular degeneration: common
variants, rare variants, copy number variations, epigenetics, and
mitochondrial genetics
SO HUMAN GENOMICS
LA English
DT Review
DE Age-related macular degeneration; Copy number variation; Genetics;
Epigenetics; Mitochondria
ID COMPLEMENT FACTOR-H; GENOME-WIDE ASSOCIATION; S-TRANSFERASE M1; PIGMENT
EPITHELIAL-CELLS; REAL-TIME PCR; DNA-DAMAGE; OXIDATIVE STRESS;
HUMAN-DISEASE; POLYMORPHISM; RISK
AB Age-related macular degeneration (AMD) is a complex and multifaceted disease involving contributions from both genetic and environmental influences. Previous work exploring the genetic contributions of AMD has implicated numerous genomic regions and a variety of candidate genes as modulators of AMD susceptibility. Nevertheless, much of this work has revolved around single-nucleotide polymorphisms (SNPs), and it is apparent that a significant portion of the heritability of AMD cannot be explained through these mechanisms. In this review, we consider the role of common variants, rare variants, copy number variations, epigenetics, microRNAs, and mitochondrial genetics in AMD. Copy number variations in regulators of complement activation genes (CFHR1 and CFHR3) and glutathione S transferase genes (GSTM1 and GSTT1) have been associated with AMD, and several additional loci have been identified as regions of potential interest but require further evaluation. MicroRNA dysregulation has been linked to the retinal pigment epithelium degeneration in geographic atrophy, ocular neovascularization, and oxidative stress, all of which are hallmarks in the pathogenesis of AMD. Certain mitochondrial DNA haplogroups and SNPs in mitochondrially encoded NADH dehydrogenase genes have also been associated with AMD. The role of these additional mechanisms remains only partly understood, but the importance of their further investigation is clear to elucidate more completely the genetic basis of AMD.
C1 [Liu, Melissa M.; Chan, Chi-Chao; Tuo, Jingsheng] NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA.
[Liu, Melissa M.] Johns Hopkins Univ, Sch Med, Baltimore, MD 21205 USA.
RP Tuo, JS (reprint author), NEI, Immunol Lab, NIH, 10-10 N103,10 Ctr Dr, Bethesda, MD 20892 USA.
EM tuoj@nei.nih.gov
OI Tuo, Jingsheng/0000-0002-1372-7810
FU NEI NIH HHS [T32 EY007143]
NR 92
TC 32
Z9 32
U1 1
U2 21
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1473-9542
J9 HUM GENOMICS
JI Hum. Genomics
PD AUG 31
PY 2012
VL 6
AR 13
DI 10.1186/1479-7364-6-13
PG 8
WC Genetics & Heredity
SC Genetics & Heredity
GA 121DK
UT WOS:000317222800001
PM 23244519
ER
PT J
AU Kelly, D
Burt, K
Missaghi, B
Barrett, L
Keynan, Y
Fowke, K
Grant, M
AF Kelly, Deborah
Burt, Kimberley
Missaghi, Bayan
Barrett, Lisa
Keynan, Yoav
Fowke, Keith
Grant, Michael
TI Responses to pandemic ASO3-adjuvanted A/California/07/09 H1N1 influenza
vaccine in human immunodeficiency virus-infected individuals
SO BMC IMMUNOLOGY
LA English
DT Article
DE HIV; influenza; pandemic; A/California/07/2009 H1N1 HA antigen; AS03 oil
in water adjuvant; inflammation; CD4(+) T cells; age
ID IMMUNE-RESPONSE; HIV; IMMUNOGENICITY; ADULTS; TRIAL; INFLAMMATION;
ACTIVATION; SAFETY
AB Background: Influenza infection may be more serious in human immunodeficiency virus (HIV)-infected individuals, therefore, vaccination against seasonal and pandemic strains is highly advised. Seasonal influenza vaccines have had no significant negative effects in well controlled HIV infection, but the impact of adjuvanted pandemic A/California/07/2009 H1N1 influenza hemaglutinin (HA) vaccine, which was used for the first time in the Canadian population as an authorized vaccine in autumn 2009, has not been extensively studied.
Objective: Assess vaccine-related effects on CD4(+) T cell counts and humoral responses to the vaccine in individuals attending the Newfoundland and Labrador Provincial HIV clinic.
Methods: A single dose of Arepanrix (TM) split vaccine including 3.75 mu g A/California/07/2009 H1N1 HA antigen and ASO3 adjuvant was administered to 81 HIV-infected individuals by intramuscular injection. Plasma samples from shortly before, and 1-5 months after vaccination were collected from 80/81 individuals to assess humoral anti-H1N1 HA responses using a sensitive microbead-based array assay. Data on CD4(+) T cell counts, plasma viral load, antiretroviral therapy and patient age were collected from clinical records of 81 individuals.
Results: Overall, 36/80 responded to vaccination either by seroconversion to H1N1 HA or with a clear increase in anti-H1N1 HA antibody levels. Approximately 1/3 (28/80) had pre-existing anti-H1N1 HA antibodies and were more likely to respond to vaccination (22/28). Responders had higher baseline CD4(+) T cell counts and responders without pre-existing antibodies against H1N1 HA were younger than either non-responders or responders with pre-existing antibodies. Compared to changes in their CD4(+) T cell counts observed over a similar time period one year later, vaccine recipients displayed a minor, transient fall in CD4(+) T cell numbers, which was greater amongst responders.
Conclusions: We observed low response rates to the 2009 pandemic influenza vaccine among HIV-infected individuals without pre-existing antibodies against H1N1 HA and a minor transient fall in CD4(+) T cell numbers, which was accentuated in responders. A single injection of the Arepanrix (TM) pandemic A/California/07/2009 H1N1 HA split vaccine may be insufficient to induce protective immunity in HIV-infected individuals without pre-existing anti-H1N1 HA responses.
C1 [Grant, Michael] Mem Univ Newfoundland & Labrador, Div BioMed Sci, St John, NF, Canada.
[Grant, Michael] Mem Univ Newfoundland, Fac Med, St John, NF, Canada.
[Kelly, Deborah] Mem Univ Newfoundland & Labrador, Sch Pharm, St John, NF, Canada.
[Kelly, Deborah; Burt, Kimberley; Missaghi, Bayan] Eastern Hlth Corp Newfoundland & Labrador, St John, NF, Canada.
[Missaghi, Bayan] Mem Univ Newfoundland & Labrador, Div Infect Dis, St John, NF, Canada.
[Barrett, Lisa] NIH, Inst Allergy & Infect Dis, Bethesda, MD 20892 USA.
[Keynan, Yoav; Fowke, Keith] Univ Manitoba, Dept Med Microbiol, Winnipeg, MB, Canada.
[Keynan, Yoav; Fowke, Keith] Univ Manitoba, Dept Community Hlth Sci, Winnipeg, MB R3T 2N2, Canada.
[Keynan, Yoav; Fowke, Keith] Univ Nairobi, Dept Med Microbiol, Nairobi, Kenya.
RP Grant, M (reprint author), Mem Univ Newfoundland & Labrador, Div BioMed Sci, St John, NF, Canada.
EM mgrant@mun.ca
OI Fowke, Keith/0000-0001-8227-6649
FU Canadian Institutes of Health Research grant [HC1-112568]
FX We would like to thank all the subjects participating in this study.
Maureen Gallant and Katrin Zipperlen sorted, coded and dispensed the
plasma samples shipped to Winnipeg for anti-H1N1 HA measurement. This
study was supported in part by Canadian Institutes of Health Research
grant #HC1-112568 awarded to MG.
NR 22
TC 6
Z9 6
U1 0
U2 4
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2172
J9 BMC IMMUNOL
JI BMC Immunol.
PD AUG 31
PY 2012
VL 13
AR 49
DI 10.1186/1471-2172-13-49
PG 9
WC Immunology
SC Immunology
GA 027JR
UT WOS:000310348900001
PM 22937824
ER
PT J
AU Hernandez-Rocamora, VM
Reija, B
Garcia, C
Natale, P
Alfonso, C
Minton, AP
Zorrilla, S
Rivas, G
Vicente, M
AF Hernandez-Rocamora, Victor M.
Reija, Belen
Garcia, Concepcion
Natale, Paolo
Alfonso, Carlos
Minton, Allen P.
Zorrilla, Silvia
Rivas, German
Vicente, Miguel
TI Dynamic Interaction of the Escherichia coli Cell Division ZipA and FtsZ
Proteins Evidenced in Nanodiscs
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID PHOSPHOLIPID-BILAYER NANODISCS; MEMBRANE-PROTEINS; IN-VITRO; RING;
RECONSTITUTION; ASSOCIATION; MONOMER; BIOLOGY
AB The full-length ZipA protein from Escherichia coli, one of the essential components of the division proto-ring that provides membrane tethering to the septation FtsZ protein, has been incorporated in single copy into nanodiscs formed by a membrane scaffold protein encircling an E. coli phospholipid mixture. This is an acellular system that reproduces the assembly of part of the cell division components. ZipA contained in nanodiscs (Nd-ZipA) retains the ability to interact with FtsZ oligomers and with FtsZ polymers. Interactions with FtsZ occur at similar strengths as those involved in the binding of the soluble form of ZipA, lacking the transmembrane region, suggesting that the transmembrane region of ZipA has little influence on the formation of the ZipA.FtsZ complex. Peptides containing partial sequences of the C terminus of FtsZ compete with FtsZ polymers for binding to Nd-ZipA. The affinity of Nd-ZipA for the FtsZ polymer formed with GTP or GMPCPP (a slowly hydrolyzable analog of GTP) is moderate (micromolar range) and of similar magnitude as for FtsZ-GDP oligomers. Polymerization does not stabilize the binding of FtsZ to ZipA. This supports the role of ZipA as a passive anchoring device for the proto-ring with little implication, if any, in the regulation of its assembly. Furthermore, it indicates that the tethering of FtsZ to the membrane shows sufficient plasticity to allow for its release from noncentral regions of the cytoplasmic membrane and its subsequent relocation to midcell when demanded by the assembly of a division ring.
C1 [Hernandez-Rocamora, Victor M.; Garcia, Concepcion; Alfonso, Carlos; Rivas, German] CSIC, Ctr Invest Biol, E-28006 Madrid, Spain.
[Reija, Belen; Zorrilla, Silvia] CSIC, Inst Quim Fis Rocasolano, E-28006 Madrid, Spain.
[Natale, Paolo; Vicente, Miguel] CSIC, Ctr Nacl Biotecnol, E-28006 Madrid, Spain.
[Minton, Allen P.] NIDDK, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA.
RP Rivas, G (reprint author), CSIC, Ctr Invest Biol, Velazquez 144, E-28006 Madrid, Spain.
EM grivas@cib.csic.es; mvicente@cnb.csic.es
RI Zorrilla, Silvia/J-9771-2014; Alfonso, Carlos/K-1316-2014;
OI Zorrilla, Silvia/0000-0002-6309-9058; Alfonso,
Carlos/0000-0001-7165-4800; Minton, Allen/0000-0001-8459-1247; Rivas,
German/0000-0003-3450-7478
FU Human Frontier Science Program [RGP0050/2010]; European Commission
[HEALTH-F3-2009-223431]; Spanish Government [BIO2008-04478-C03,
CSIC-PIE-201020I001, BFU2010-14910, BIO2011-28941-C03]; NIDDK, National
Institutes of Health
FX This work was supported in part by the Human Frontier Science Program
through Grant RGP0050/2010, the European Commission through Contract
HEALTH-F3-2009-223431 (both to M. V. and G. R.), and the Spanish
Government through Grants BIO2008-04478-C03 (to M. V. and G. R.),
CSIC-PIE-201020I001 (to C. A.), BFU2010-14910 (to S. Z.), and
BIO2011-28941-C03 (to M. V., G. R., and S. Z.).; Supported by the
Intramural Research Program of the NIDDK, National Institutes of Health.
NR 24
TC 21
Z9 21
U1 1
U2 19
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD AUG 31
PY 2012
VL 287
IS 36
BP 30097
EP 30104
DI 10.1074/jbc.M112.388959
PG 8
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 003AF
UT WOS:000308579800005
PM 22787144
ER
PT J
AU Wang, L
Jia, Y
Rogers, H
Wu, YP
Huang, SM
Noguchi, CT
AF Wang, Li
Jia, Yi
Rogers, Heather
Wu, Yun-Ping
Huang, Suming
Noguchi, Constance Tom
TI GATA-binding Protein 4 (GATA-4) and T-cell Acute Leukemia 1 (TAL1)
Regulate Myogenic Differentiation and Erythropoietin Response via
Cross-talk with Sirtuin1 (Sirt1)
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID HEART TUBE FORMATION; SKELETAL-MUSCLE; TRANSCRIPTION FACTOR; VENTRAL
MORPHOGENESIS; HISTONE DEACETYLASES; GENE DISRUPTION; SATELLITE CELLS;
MYOD; EXPRESSION; RECEPTOR
AB Erythropoietin (EPO), the cytokine required for erythrocyte production, contributes to muscle progenitor cell proliferation and delay myogenic differentiation. However, the underlying mechanism is not yet fully understood. Here, we report that EPO changes the skeletal myogenic regulatory factor expression program and delays differentiation via induction of GATA-4 and the basic helix-loop-helix TAL1 and that knockdown of both factors promotes differentiation. EPO increases the Sirt1 level, a NAD(+)-dependent deacetylase, and also induces the NAD(+)/NADH ratio that further increases Sirt1 activity. Sirt1 knockdown reduced GATA-4 and TAL1 expression, impaired EPO effect on delayed myogenic differentiation, and the Sirt1 knockdown effect was abrogated when combined with overexpression of GATA-4 or TAL1. GATA-4 interacts with Sirt1 and targets Sirt1 to the myogenin promoter and represses myogenin expression, whereas TAL1 inhibits myogenin expression by decreasing MyoD binding to and activation of the myogenin promoter. Sirt1 was found to bind to the GATA-4 promoter to directly regulate GATA-4 expression and GATA-4 binds to the TAL1 promoter to regulate TAL1 expression positively. These data suggest that GATA-4, TAL1, and Sirt1 cross-talk each other to regulate myogenic differentiation and mediate EPO activity during myogenic differentiation with Sirt1 playing a role upstream of GATA-4 and TAL1. Taken together, our findings reveal a novel role for GATA-4 and TAL1 to affect skeletal myogenic differentiation and EPO response via cross-talk with Sirt1.
C1 [Wang, Li; Jia, Yi; Rogers, Heather; Noguchi, Constance Tom] NIDDK, Mol Med Branch, NIH, Bethesda, MD 20892 USA.
[Wu, Yun-Ping] NIDDK, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA.
[Huang, Suming] Univ Florida, Coll Med, Dept Biochem & Mol Biol, Gainesville, FL 32610 USA.
[Huang, Suming] Univ Florida, Coll Med, Shands Canc Ctr, Gainesville, FL 32610 USA.
RP Noguchi, CT (reprint author), Bldg 10,Rm 9N319,10 Ctr Dr,MSC 1822, Bethesda, MD 20892 USA.
EM connien@niddk.nih.gov
FU National Institutes of Health Intramural Research Program of the NIDDK
FX This work was supported, in whole or in part, by the National Institutes
of Health Intramural Research Program of the NIDDK.
NR 55
TC 11
Z9 11
U1 0
U2 0
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD AUG 31
PY 2012
VL 287
IS 36
BP 30157
EP 30169
DI 10.1074/jbc.M112.376640
PG 13
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 003AF
UT WOS:000308579800011
PM 22773876
ER
PT J
AU Bandyopadhyay, BC
Swaim, WD
Sarkar, A
Liu, XB
Ambudkar, IS
AF Bandyopadhyay, Bidhan C.
Swaim, William D.
Sarkar, Ankana
Liu, Xibao
Ambudkar, Indu S.
TI Extracellular Ca2+ Sensing in Salivary Ductal Cells
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID CALCIUM-TRANSPORT; EPITHELIAL-CELLS; TRPC3 CHANNELS; PLASMA-MEMBRANE;
FLUID SECRETION; CATION CHANNEL; AMINO-ACIDS; RECEPTOR; GLAND;
LOCALIZATION
AB Ca2+ is secreted from the salivary acinar cells as an ionic constituent of primary saliva. Ions such as Na+ and Cl- get reabsorbed whereas primary saliva flows through the salivary ductal system. Although earlier studies have shown that salivary [Ca2+] decreases as it flows down the ductal tree into the oral cavity, ductal reabsorption of Ca2+ remains enigmatic. Here we report a potential role for the G protein-coupled receptor, calcium-sensing receptor (CSR), in the regulation of Ca2+ reabsorption by salivary gland ducts. Our data show that CSR is present in the apical region of ductal cells where it is co-localized with transient receptor potential canonical 3 (TRPC3). CSRis activated in isolated salivary gland ducts as well as a ductal cell line (SMIE) by altering extracellular [Ca2+] or by aromatic amino acid, L-phenylalanine (L-Phe, endogenous component of saliva), as well as neomycin. CSR activation leads to Ca2+ influx that, in polarized cells grown on a filter support, is initiated in the luminal region. Weshow that TRPC3 contributes to Ca2+ entry triggered by CSR activation. Further, stimulation of CSR in SMIE cells enhances the CSR-TRPC3 association as well as surface expression of TRPC3. Together our findings suggest that CSR could serve as a Ca2+ sensor in the luminal membrane of salivary gland ducts and regulate reabsorption of [Ca2+] from the saliva via TRPC3, thus contributing to maintenance of salivary [Ca2+]. CSR could therefore be a potentially important protective mechanism against formation of salivary gland stones (sialolithiasis) and infection (sialoadenitis).
C1 [Bandyopadhyay, Bidhan C.] Vet Affairs Med Ctr, Res Serv, Calcium Signaling Lab, Washington, DC 20422 USA.
[Bandyopadhyay, Bidhan C.; Sarkar, Ankana] Georgetown Univ, Dept Physiol & Pharmacol, Washington, DC 20007 USA.
[Swaim, William D.; Liu, Xibao; Ambudkar, Indu S.] NIDCR, Mol Physiol & Therapeut Branch, NIH, Bethesda, MD 20892 USA.
RP Bandyopadhyay, BC (reprint author), DVA Med Ctr, Calcium Signaling Lab, Res Serv 151, 50 Irving St NW, Washington, DC 20422 USA.
EM bidhan.bandyopadhyay@va.gov
FU National Institutes of Health through NIDCR [DE 019524]; NIDCR
Intramural Research
FX This study was supported, in whole or in part, by National Institutes of
Health Grant DE 019524 through the NIDCR ( to B. C. B) and by NIDCR
Intramural Research ( to I. S. A.).
NR 50
TC 7
Z9 7
U1 3
U2 6
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD AUG 31
PY 2012
VL 287
IS 36
BP 30305
EP 30316
DI 10.1074/jbc.M112.394122
PG 12
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 003AF
UT WOS:000308579800023
PM 22778254
ER
PT J
AU Oh, HM
Yu, CR
Dambuza, I
Marrero, B
Egwuagu, CE
AF Oh, Hyun-Mee
Yu, Cheng-Rong
Dambuza, Ivy
Marrero, Bernadette
Egwuagu, Charles E.
TI STAT3 Protein Interacts with Class O Forkhead Transcription Factors in
the Cytoplasm and Regulates Nuclear/Cytoplasmic Localization of FoxO1
and FoxO3a Proteins in CD4(+) T Cells
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID NF-KAPPA-B; INTERLEUKIN-10; P27(KIP1); SURVIVAL; BINDING; SYSTEM; IL-2
AB An important feature of the adaptive immune response is its remarkable capacity to regulate the duration of inflammatory responses, and effector T cells have been shown to limit excessive immune responses by producing anti-inflammatory cytokines such as IL-10 and IL-27. However, how anti-inflammatory cytokines mediate their suppressive activities is not well understood. In this study, we show that STAT3 contributes to mechanisms that control the duration of T cell proliferation by regulating the subcellular location of FoxO1 and FoxO3a, two Class O Forkhead transcription factors that mediate lymphocyte quiescence and inhibit T cell activation. We show that active FoxO1 and FoxO3a reside exclusively in the nucleus of naive T cells whereas inactive pFoxO1 and pFoxO3a were most abundant in activated T cells and sequestered in their cytoplasm in association with unphosphorylated STAT3 (U-STAT3) and 14-3-3. We further show that FoxO1/FoxO3a rapidly relocalized into the nucleus in response to pSTAT3 activation by IL-6 or IL-10, and the accumulation of FoxO1/FoxO3a in their nuclei coincided with increased expression of p27(Kip1) and p21(WAF1). STAT3 inhibitors completely abrogated cytokine-induced translocation of FoxO1/FoxO3a into the nucleus. In naive or resting STAT3-deficient T cells, expression of pFoxO1/pFoxO3a was predominantly in the cytoplasm and correlated with defects in p27(Kip1) and p21(WAF1) expression, suggesting requirement of STAT3 for importation or retention of FoxO in the nucleus and attenuation of lymphocyte proliferation. Taken together, these results suggest that U-STAT3 collaborates with 14-3-3 to sequester pFoxO1/pFoxO3a in cytoplasm and thus prolong T cell activation, whereas pSTAT3 activation by anti-inflammatory cytokines would curtail the duration of TCR activation and re-establish lymphocyte quiescence by inducing nuclear localization of FoxO1/FoxO3a and FoxO-mediated expression of growth-inhibitory proteins.
C1 [Egwuagu, Charles E.] NEI, Mol Immunol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA.
[Oh, Hyun-Mee] Korea Res Inst Biosci & BioTechnol, Bioind Proc Res Ctr, Jeongeup Si 580185, Jeonbuk, South Korea.
RP Egwuagu, CE (reprint author), NEI, Mol Immunol Sect, Immunol Lab, NIH, Bldg 10,Rm 10N109A,10 Ctr Dr, Bethesda, MD 20892 USA.
EM egwuaguc@nei.nih.gov
FU National Institutes of Health NEI Research Program; National Institutes
of Health Intramural Research Program
FX This work was supported by the National Institutes of Health NEI and
Intramural Research Programs.
NR 29
TC 11
Z9 11
U1 0
U2 7
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD AUG 31
PY 2012
VL 287
IS 36
BP 30436
EP 30443
DI 10.1074/jbc.M112.359661
PG 8
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 003AF
UT WOS:000308579800036
PM 22761423
ER
PT J
AU Chander, P
Gentleman, S
Poliakov, E
Redmond, TM
AF Chander, Preethi
Gentleman, Susan
Poliakov, Eugenia
Redmond, T. Michael
TI Aromatic Residues in the Substrate Cleft of RPE65 Protein Govern Retinol
Isomerization and Modulate Its Progression
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID VISUAL CYCLE; ISOMEROHYDROLASE ACTIVITY; CAROTENOID OXYGENASE; PIGMENT
EPITHELIUM; ISOMERASE; MODEL; COMPLEXES; EFFICIENT; ENZYME; SERVER
AB Previously, we showed that mutating RPE65 residue Phe-103 preferentially produces 13-cis-retinol instead of 11-cis-retinol, supporting a carbocation/radical cation mechanism of retinol isomerization. We asked whether this modulation of specificity can occur with residues other than Phe-103 and what role it plays in substrate binding and isomerization. We modeled the substrate-binding cleft of RPE65 to identify residues lining its surface. Many are phenylalanines and tyrosines, including three Phe residues (Phe-61, Phe-312, and Phe-526) forming an arch-like arrangement astride the cleft and Tyr-338. Also, Phe-418 sits at the neck of the cleft, lending a bend to the volume enclosed by the cleft. All mutations of Phe-61, Phe-312, and Phe-418 result in severely impaired or inactive enzyme. However, mutation of Phe-526 and Tyr-338, like Phe-103, decreases 11-cis-retinol formation, whereas increasing the 13-cis isomer. Significantly, 2 of these 3 residues, Phe-103 and Tyr-338, are located on putatively mobile interstrand loops. We propose that residual densities located in the binding cleft of the RPE65 structure represents a post-cleavage snapshot consistent not only with a fatty acid product, as originally modeled, but also an 11-cis-retinol product. Substrate docking simulations permit 11-cis- or 13-cis-retinyl ester binding in this relatively closed cleft, with the latter favored in F103L, F526A, and Y338A mutant structures, but prohibit binding of all-trans-retinyl ester, suggesting that isomerization occurs early in the temporal sequence, with O-alkyl ester cleavage occurring later. These findings provide insight into the mechanism of isomerization central to the visual cycle.
C1 [Chander, Preethi; Gentleman, Susan; Poliakov, Eugenia; Redmond, T. Michael] NEI, Lab Retinal Cell & Mol Biol, NIH, Bethesda, MD 20892 USA.
RP Redmond, TM (reprint author), NEI, Lab Retinal Cell & Mol Biol, NIH, Bldg 6,Rm 117A, Bethesda, MD 20892 USA.
EM redmond@helix.nih.gov
OI Redmond, T. Michael/0000-0002-1813-5291
FU National Institutes of Health Intramural Research Program of the NEI
FX This work was supported, in whole or in part, by the National Institutes
of Health Intramural Research Program of the NEI.
NR 31
TC 12
Z9 12
U1 0
U2 2
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD AUG 31
PY 2012
VL 287
IS 36
BP 30552
EP 30559
DI 10.1074/jbc.M112.364596
PG 8
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 003AF
UT WOS:000308579800047
PM 22745121
ER
PT J
AU Gao, R
Huang, SYN
Marchand, C
Pommier, Y
AF Gao, Rui
Huang, Shar-yin N.
Marchand, Christophe
Pommier, Yves
TI Biochemical Characterization of Human Tyrosyl-DNA Phosphodiesterase 2
(TDP2/TTRAP) A Mg2+/Mn2+-DEPENDENT PHOSPHODIESTERASE SPECIFIC FOR THE
REPAIR OF TOPOISOMERASE CLEAVAGE COMPLEXES
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID HUMAN APURINIC/APYRIMIDINIC ENDONUCLEASE; RECEPTOR-ASSOCIATED FACTORS;
BODIES-ASSOCIATED PROTEIN; DIVALENT METAL-IONS; VERTEBRATE CELLS;
ACTIVE-SITE; I-TASSER; TTRAP; DAMAGE; TDP1
AB TDP2 is a multifunctional enzyme previously known for its role in signal transduction as TRAF and TNF receptor-associated protein (TTRAP) and ETS1-associated protein 2 (EAPII). The gene has recently been renamed TDP2 because it plays a critical role for the repair of topoisomerase II cleavage complexes (Top2cc) and encodes an enzyme that hydrolyzes 5'-tyrosine-DNA adducts that mimic abortive Top2cc. Here we further elucidate the DNA-processing activities of human recombinant TDP2 and its biochemical characteristics. The preferred substrate for TDP2 is single-stranded DNA or duplex DNA with a four-base pair overhang, which is consistent with the known structure of Top2cc or Top3cc. The k(cat)/K-m of TDP1 and TDP2 was determined. It was found to be 4 x 10(5) s(-1)M(-1) for TDP2 using single-stranded 5'-tyrosyl-DNA. The processing of substrates as short as five nucleotides long suggests that TDP2 can directly bind DNA ends. 5'-Phosphodiesterase activity requires a phosphotyrosyl linkage and tolerates an extended group attached to the tyrosine. TDP2 requires Mg2+ or Mn2+ for efficient catalysis but is weakly active with Ca2+ or Zn2+. Titration with Ca2+ demonstrates a two-metal binding site in TDP2. Sequence alignment suggests that TDP2 contains four conserved catalytic motifs shared by Mg2+-dependent endonucleases, such as APE1. Substitutions at each of the four catalytic motifs identified key residues Asn-120, Glu-152, Asp-262, and His-351, whose mutation to alanine significantly reduced or completely abolished enzymatic activity. Our study characterizes the substrate specificity and kinetic parameters of TDP2. In addition, a two-metal catalytic mechanism is proposed.
C1 [Gao, Rui; Huang, Shar-yin N.; Marchand, Christophe; Pommier, Yves] NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Pommier, Y (reprint author), NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM pommier@nih.gov
FU Center for Cancer Research, Intramural Program of the NCI, National
Institutes of Health
FX This work was supported, in whole or in part, by the Center for Cancer
Research, Intramural Program of the NCI, National Institutes of Health.
NR 44
TC 25
Z9 28
U1 1
U2 11
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD AUG 31
PY 2012
VL 287
IS 36
BP 30842
EP 30852
DI 10.1074/jbc.M112.393983
PG 11
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 003AF
UT WOS:000308579800072
PM 22822062
ER
PT J
AU Zheng, QX
Ren, YP
Tzekov, R
Zhang, YP
Chen, B
Hou, JP
Zhao, CH
Zhu, JL
Zhang, Y
Dai, XF
Ma, S
Li, J
Pang, JJ
Qu, J
Li, WS
AF Zheng, Qinxiang
Ren, Yueping
Tzekov, Radouil
Zhang, Yuanping
Chen, Bo
Hou, Jiangping
Zhao, Chunhui
Zhu, Jiali
Zhang, Ying
Dai, Xufeng
Ma, Shan
Li, Jia
Pang, Jijing
Qu, Jia
Li, Wensheng
TI Differential Proteomics and Functional Research following Gene Therapy
in a Mouse Model of Leber Congenital Amaurosis
SO PLOS ONE
LA English
DT Article
ID CANINE MODEL; RETINAL DEGENERATION; CHILDHOOD BLINDNESS; RPE65
MUTATIONS; RESTORES VISION; PEROXIREDOXIN 6; LIGHT DAMAGE; MURINE MODEL;
RAT RETINA; CELL-DEATH
AB Leber congenital amaurosis (LCA) is one of the most severe forms of inherited retinal degeneration and can be caused by mutations in at least 15 different genes. To clarify the proteomic differences in LCA eyes, a cohort of retinal degeneration 12 (rd12) mice, an LCA2 model caused by a mutation in the RPE65 gene, were injected subretinally with an AAV vector (scAAV5-smCBA-hRPE65) in one eye, while the contralateral eye served as a control. Proteomics were compared between untreated rd12 and normal control retinas on P14 and P21, and among treated and untreated rd12 retinas and control retinas on P42. Gene therapy in rd12 mice restored retinal function in treated eyes, which was demonstrated by electroretinography (ERG). Proteomic analysis successfully identified 39 proteins expressed differently among the 3 groups. The expression of 3 proteins involved in regulation of apoptosis and neuroptotection (alpha A crystallin, heat shock protein 70 and peroxiredoxin 6) were investigated further. Immunofluorescence, Western blot and real-time PCR confirmed the quantitative changes in their expression. Furthermore, cell culture studies suggested that peroxiredoxin 6 could act in an antioxidant role in rd12 mice. Our findings support the feasibility of gene therapy in LCA2 patients and support a role for alpha A crystallin, heat shock protein 70 and peroxiredoxin 6 in the pathogenetic mechanisms involved in LCA2 disease process.
C1 [Zheng, Qinxiang; Ren, Yueping; Hou, Jiangping; Zhao, Chunhui; Zhu, Jiali; Zhang, Ying; Dai, Xufeng; Pang, Jijing; Qu, Jia; Li, Wensheng] Wenzhou Med Coll, Hosp Eye, Wenzhou, Peoples R China.
[Tzekov, Radouil] Roskamp Inst, Sarasota, FL USA.
[Zhang, Yuanping] Kunming Med Coll, Affiliated Hosp 2, Dept Ophthalmol, Kunming, Peoples R China.
[Chen, Bo] Yale Univ, Sch Med, Dept Ophthalmol & Visual Sci, New Haven, CT 06510 USA.
[Ma, Shan; Li, Jia] Univ Massachusetts, Sch Med, Dept Ophthalmol, Worcester, MA USA.
[Pang, Jijing] Univ Florida, Coll Med, Dept Ophthalmol, Gainesville, FL 32610 USA.
[Li, Wensheng] NEI, Neurobiol Neurodegenerat & Repair Lab, Retinal Cell Biol & Degenerat Sect, NIH, Bethesda, MD 20892 USA.
RP Zheng, QX (reprint author), Wenzhou Med Coll, Hosp Eye, Wenzhou, Peoples R China.
EM jqu@wzmc.net; drlws@163.net
OI Tzekov, Radouil/0000-0002-3662-9818
FU Major Projects of the National Science and Technology of China
[2009ZX09503]; Specilized Research Fund for the Doctoral Program of
Higher Education [20103321110002]; Key Projects of National High-Tech
R&D Program (863 Program) of China [2007AA021004]; Eye Hospital, School
of Ophthalmology & Optometry, Wenzhou Medical College, Wenzhou, China
FX This research was supported by grants of Major Projects of the National
Science and Technology of China (No: 2009ZX09503), Specilized Research
Fund for the Doctoral Program of Higher Education (No: 20103321110002),
Key Projects of National High-Tech R&D Program (863 Program) of China
(No: 2007AA021004), retinal gene therapy study grants from Eye Hospital,
School of Ophthalmology & Optometry, Wenzhou Medical College, Wenzhou,
China. The funders had no role in study design, data collection and
analysis, decision to publish, or preparation of the manuscript.
NR 57
TC 7
Z9 7
U1 0
U2 10
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD AUG 31
PY 2012
VL 7
IS 8
AR e44855
DI 10.1371/journal.pone.0044855
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 998EY
UT WOS:000308221300106
PM 22953002
ER
PT J
AU Sung, MH
Hager, GL
AF Sung, Myong-Hee
Hager, Gordon L.
TI Nonlinear Dependencies of Biochemical Reactions for Context-specific
Signaling Dynamics
SO SCIENTIFIC REPORTS
LA English
DT Article
ID NF-KAPPA-B; GENE-EXPRESSION; NETWORKS; OSCILLATIONS; MODULE
AB Mathematical modeling can provide unique insights and predictions about a signaling pathway. Parameter variations allow identification of key reactions that govern signaling features such as the response time that may have a direct impact on the functional outcome. The effect of varying one parameter, however, may depend on values of another. To address the issue, we performed multi-parameter variations of an experimentally validated mathematical model of NF-kappa B regulatory network, and analyzed the inter-relationships of the parameters in shaping key dynamic features. We find that nonlinear dependencies are ubiquitous among parameters. Such phenomena may underlie the emergence of cell type-specific behaviors from essentially the same molecular network. Our results from a multivariate ensemble of models highlight the hypothesis that cell type specificity in signaling phenotype can arise from quantitatively altered strength of reactions in the pathway, in the absence of tissue-specific factors that re-wire the network for a new topology.
C1 [Sung, Myong-Hee; Hager, Gordon L.] NCI, Lab Receptor Biol & Gene Express, NIH, Bethesda, MD 20892 USA.
RP Sung, MH (reprint author), NCI, Lab Receptor Biol & Gene Express, NIH, Bethesda, MD 20892 USA.
EM sungm@mail.nih.gov
FU National Institutes of Health
FX We thank Alessandra Agresti for helpful discussions. This work was
supported in part by the Intramural Research Program of the National
Institutes of Health.
NR 21
TC 2
Z9 2
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2045-2322
J9 SCI REP-UK
JI Sci Rep
PD AUG 31
PY 2012
VL 2
AR 616
DI 10.1038/srep00616
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 000YU
UT WOS:000308427800001
PM 22943002
ER
PT J
AU Marks, MA
Eby, Y
Howard, R
Gravitt, PE
AF Marks, Morgan A.
Eby, Yolanda
Howard, Roslyn
Gravitt, Patti E.
TI Comparison of normalization methods for measuring immune markers in
cervical secretion specimens
SO JOURNAL OF IMMUNOLOGICAL METHODS
LA English
DT Article
DE Cytokines; Cervical secretions; Ophthalmic sponges; Weight adjustment;
Protein adjustment
ID FEMALE GENITAL-TRACT; VAGINAL SECRETIONS; WOMEN; COLLECTION;
IMMUNOGLOBULINS; CYTOKINE; ISSUES; HIV
AB Ophthalmic sponges are used to collect undiluted cervical secretions for assessment of markers of genital tract immunity. Heterogeneity in absorbed and extracted sample volumes requires normalization in order to make valid inter-individual comparisons. We evaluated the performance of adjustment by weight and total protein on normalizing inter-individual variability of immune marker measurement due to differences in volume collection. Normalization to total protein resulted in a minimal loss of usable specimens and a significant reduction in the correlation of immune marker concentration to specimen weight compared to weight adjustment. Total protein normalization appeared to be more effective than weight adjustment in reducing the dependence of cervical immune marker concentrations on differences in specimen volume. (C) 2012 Elsevier B.V. All rights reserved.
C1 [Eby, Yolanda; Howard, Roslyn; Gravitt, Patti E.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA.
[Marks, Morgan A.] NCI, Div Canc Epidemiol & Genet, Rockville, MD USA.
[Gravitt, Patti E.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Mol Microbiol & Immunol, Baltimore, MD 21205 USA.
RP Gravitt, PE (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, 615 N Wolfe St,Rm E6148, Baltimore, MD 21205 USA.
EM pgravitt@jhsph.edu
FU US National Cancer Institute [R01 CA123467]; Institutional Research
Cancer Epidemiology Fellowship; National Cancer Institute [T32
CA0009314]
FX This work was supported by the US National Cancer Institute R01 CA123467
and the Institutional Research Cancer Epidemiology Fellowship funded by
the National Cancer Institute T32 CA0009314.
NR 14
TC 6
Z9 6
U1 0
U2 1
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0022-1759
J9 J IMMUNOL METHODS
JI J. Immunol. Methods
PD AUG 31
PY 2012
VL 382
IS 1-2
BP 211
EP 215
DI 10.1016/j.jim.2012.05.012
PG 5
WC Biochemical Research Methods; Immunology
SC Biochemistry & Molecular Biology; Immunology
GA 983AN
UT WOS:000307088700022
PM 22677266
ER
PT J
AU Youle, RJ
van der Bliek, AM
AF Youle, Richard J.
van der Bliek, Alexander M.
TI Mitochondrial Fission, Fusion, and Stress
SO SCIENCE
LA English
DT Review
ID PARKIN-MUTANTS; AUTOPHAGY; DEGRADATION; SEGREGATION; DYSFUNCTION;
MUTATIONS; CELLS; DROSOPHILA-PINK1; COMPLEMENTATION; PHOSPHORYLATION
AB Mitochondrial fission and fusion play critical roles in maintaining functional mitochondria when cells experience metabolic or environmental stresses. Fusion helps mitigate stress by mixing the contents of partially damaged mitochondria as a form of complementation. Fission is needed to create new mitochondria, but it also contributes to quality control by enabling the removal of damaged mitochondria and can facilitate apoptosis during high levels of cellular stress. Disruptions in these processes affect normal development, and they have been implicated in neurodegenerative diseases, such as Parkinson's.
C1 [Youle, Richard J.] NINDS, Biochem Sect, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA.
[van der Bliek, Alexander M.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Biol Chem, Los Angeles, CA 90095 USA.
RP Youle, RJ (reprint author), NINDS, Biochem Sect, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA.
EM youler@ninds.nih.gov; avan@mednet.ucla.edu
FU Intramural Program of the National Institute of Neurological Disorders
and Stroke; NIH [GM051866]; NSF [0552271]
FX We thank members of the Youle lab for thoughtful comments. This work was
supported by Intramural Program of the National Institute of
Neurological Disorders and Stroke and grants from the NIH (GM051866) and
the NSF (0552271) to A.M.v.d.B.
NR 45
TC 552
Z9 567
U1 40
U2 195
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 0036-8075
J9 SCIENCE
JI Science
PD AUG 31
PY 2012
VL 337
IS 6098
BP 1062
EP 1065
DI 10.1126/science.1219855
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 996WP
UT WOS:000308125800037
PM 22936770
ER
PT J
AU Naik, S
Bouladoux, N
Wilhelm, C
Molloy, MJ
Salcedo, R
Kastenmuller, W
Deming, C
Quinones, M
Koo, L
Conlan, S
Spencer, S
Hall, JA
Dzutsev, A
Kong, H
Campbell, DJ
Trinchieri, G
Segre, JA
Belkaid, Y
AF Naik, Shruti
Bouladoux, Nicolas
Wilhelm, Christoph
Molloy, Michael J.
Salcedo, Rosalba
Kastenmuller, Wolfgang
Deming, Clayton
Quinones, Mariam
Koo, Lily
Conlan, Sean
Spencer, Sean
Hall, Jason A.
Dzutsev, Amiran
Kong, Heidi
Campbell, Daniel J.
Trinchieri, Giorgio
Segre, Julia A.
Belkaid, Yasmine
TI Compartmentalized Control of Skin Immunity by Resident Commensals
SO SCIENCE
LA English
DT Article
ID REGULATORY T-CELLS; HUMAN MICROBIOME; DENDRITIC CELLS; INNATE IMMUNITY;
SYSTEM; RECOGNITION; DIVERSITY; INTESTINE; INFECTION; RESPONSES
AB Intestinal commensal bacteria induce protective and regulatory responses that maintain host-microbial mutualism. However, the contribution of tissue-resident commensals to immunity and inflammation at other barrier sites has not been addressed. We found that in mice, the skin microbiota have an autonomous role in controlling the local inflammatory milieu and tuning resident T lymphocyte function. Protective immunity to a cutaneous pathogen was found to be critically dependent on the skin microbiota but not the gut microbiota. Furthermore, skin commensals tuned the function of local T cells in a manner dependent on signaling downstream of the interleukin-1 receptor. These findings underscore the importance of the microbiota as a distinctive feature of tissue compartmentalization, and provide insight into mechanisms of immune system regulation by resident commensal niches in health and disease.
C1 [Naik, Shruti; Bouladoux, Nicolas; Wilhelm, Christoph; Molloy, Michael J.; Spencer, Sean; Belkaid, Yasmine] NIAID, Mucosal Immun Sect, Parasit Dis Lab, Bethesda, MD 20892 USA.
[Naik, Shruti; Spencer, Sean] Univ Penn, Immunol Grad Grp, Philadelphia, PA 19104 USA.
[Salcedo, Rosalba; Dzutsev, Amiran; Trinchieri, Giorgio] NCI, Canc & Inflammat Program, Ctr Canc Res, Frederick, MD 21702 USA.
[Salcedo, Rosalba; Dzutsev, Amiran] NCI, SAIC Frederick Inc, Frederick, MD 21701 USA.
[Kastenmuller, Wolfgang] NIAID, Lymphocyte Biol Sect, Immunol Lab, Bethesda, MD 20892 USA.
[Deming, Clayton; Conlan, Sean; Segre, Julia A.] NHGRI, Genet & Mol Biol Branch, Bethesda, MD 20892 USA.
[Quinones, Mariam] NIAID, Bioinformat & Computat Biosci Branch, Bethesda, MD 20892 USA.
[Koo, Lily] NIAID, Res Technol Branch, Bethesda, MD 20892 USA.
[Hall, Jason A.] NYU, Sch Med, Skirball Inst Biomol Med, Kimmel Ctr Biol & Med,Mol Pathogenesis Program, New York, NY 10016 USA.
[Kong, Heidi] NCI, Dermatol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Campbell, Daniel J.] Benaroya Res Inst, Seattle, WA 98101 USA.
[Campbell, Daniel J.] Univ Washington, Sch Med, Dept Immunol, Seattle, WA 98195 USA.
RP Belkaid, Y (reprint author), NIAID, Mucosal Immun Sect, Parasit Dis Lab, Bethesda, MD 20892 USA.
EM ybelkaid@niaid.nih.gov
OI Kong, Heidi/0000-0003-4424-064X
FU Division of Intramural Research of the National Institute of Allergy and
Infectious Diseases (NIAID); National Human Genome Research Institute,
the National Cancer Institute, NIH [F30 DK094708]; Human Frontier
Science Program
FX Supported by the Division of Intramural Research of the National
Institute of Allergy and Infectious Diseases (NIAID) and by the National
Human Genome Research Institute, the National Cancer Institute, NIH
grant F30 DK094708 (S. S.), and the Human Frontier Science Program (C.
W.). We thank the NIAID gnotobiotic facility staff, in particular C.
Acevedo and D. Trageser-Cesler; K. Holmes and the NIAID sorting
facility; K. Beacht, B. Kelsall, T. Tamachi, C. Brown, J. Benchley, A.
MacDonald, L. Mijares, K. Shenderov, and A. Sher; and Yakult Central
Institute for Microbiological Research for sharing SFB via a material
transfer agreement. DNA sequence data are available via GenBank
(accession no. SRS345653). The data reported in this paper are tabulated
in the main paper and in the supplementary materials.
NR 33
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Z9 264
U1 16
U2 100
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 31
PY 2012
VL 337
IS 6098
BP 1115
EP 1119
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 996WP
UT WOS:000308125800053
PM 22837383
ER
PT J
AU Barone-Adesi, F
Chapman, RS
Silverman, DT
He, XZ
Hu, W
Vermeulen, R
Ning, BF
Fraumeni, JF
Rothman, N
Lan, Q
AF Barone-Adesi, Francesco
Chapman, Robert S.
Silverman, Debra T.
He, Xinghzhou
Hu, Wei
Vermeulen, Roel
Ning, Bofu
Fraumeni, Joseph F., Jr.
Rothman, Nathaniel
Lan, Qing
TI Risk of lung cancer associated with domestic use of coal in Xuanwei,
China: retrospective cohort study
SO BRITISH MEDICAL JOURNAL
LA English
DT Article
ID HOUSEHOLD STOVE IMPROVEMENT; INDOOR AIR-POLLUTION; TIN MINERS;
MORTALITY; MUTATIONS; SMOKING
AB Objective To estimate the risk of lung cancer associated with the use of different types of coal for household cooking and heating.
Setting Xuanwei County, Yunnan Province, China.
Design Retrospective cohort study (follow-up 1976-96) comparing mortality from lung cancer between lifelong users of "smoky coal" (bituminous) and "smokeless coal" (anthracite).
Participants 27 310 individuals using smoky coal and 9962 individuals using smokeless coal during their entire life.
Main outcome measures Primary outcomes were absolute and relative risk of death from lung cancer among users of different types of coal. Unadjusted survival analysis was used to estimate the absolute risk of lung cancer, while Cox regression models compared mortality hazards for lung cancer between smoky and smokeless coal users.
Results Lung cancer mortality was substantially higher among users of smoky coal than users of smokeless coal. The absolute risks of lung cancer death before 70 years of age for men and women using smoky coal were 18% and 20%, respectively, compared with less than 0.5% among smokeless coal users of both sexes. Lung cancer alone accounted for about 40% of all deaths before age 60 among individuals using smoky coal. Compared with smokeless coal, use of smoky coal was associated with an increased risk of lung cancer death (for men, hazard ratio 36 (95% confidence interval 20 to 65); for women, 99 (37 to 266)).
Conclusions In Xuanwei, the domestic use of smoky coal is associated with a substantial increase in the absolute lifetime risk of developing lung cancer and is likely to represent one of the strongest effects of environmental pollution reported for cancer risk. Use of less carcinogenic types of coal could translate to a substantial reduction of lung cancer risk.
C1 [Barone-Adesi, Francesco; Silverman, Debra T.; Hu, Wei; Fraumeni, Joseph F., Jr.; Rothman, Nathaniel; Lan, Qing] NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20892 USA.
[Chapman, Robert S.] Chulalongkorn Univ, Coll Publ Hlth Sci, Bangkok 10330, Thailand.
[He, Xinghzhou] Chinese Acad Prevent Med, Inst Environm Hlth & Engn, Beijing 100050, Peoples R China.
[Vermeulen, Roel] Univ Utrecht, Div Environm Epidemiol, Inst Risk Assessment Sci, NL-3584 CK Utrecht, Netherlands.
[Ning, Bofu] Xuanwei Ctr Dis Control, Qujing 655400, Yunnan, Peoples R China.
RP Barone-Adesi, F (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, DHHS, 6120 Executive Blv,EPS 8015, Bethesda, MD 20892 USA.
EM baroneadesif@mail.nih.gov
RI Hu, Wei/M-3524-2013; Vermeulen, Roel/F-8037-2011
OI Vermeulen, Roel/0000-0003-4082-8163
FU Chinese Academy of Preventive Medicine, Beijing, China; Yunnan Province
Antiepidemic Station, Kunming, China; US Environmental Protection Agency
[5D2290NFFX]; Intramural Research Program of the National Cancer
Institute, National Institutes of Health
FX The study was supported by the Chinese Academy of Preventive Medicine,
Beijing, China, by the Yunnan Province Antiepidemic Station, Kunming,
China, and by contract 5D2290NFFX from the US Environmental Protection
Agency. This study was also supported by the Intramural Research Program
of the National Cancer Institute, National Institutes of Health. The
Xuanwei cohort study has been reviewed by the US Environmental
Protection Agency and the National Cancer Institute. The contents do not
necessarily reflect the views or policies of these institutions, nor
does mention of trade names or commercial products constitute
endorsement or recommendation for use. The funding source had no role in
design or conduct of the study; collection, management, analysis, or
interpretation of the data; preparation, review, or approval of the
manuscript.
NR 24
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Z9 36
U1 2
U2 24
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 1756-1833
J9 BRIT MED J
JI Br. Med. J.
PD AUG 30
PY 2012
VL 345
AR e5414
DI 10.1136/bmj.e5414
PG 10
WC Medicine, General & Internal
SC General & Internal Medicine
GA 036SM
UT WOS:000311050800002
PM 22936785
ER
PT J
AU Simone, CB
Morris, JC
Stewart, DM
Urquhart, NE
Janik, JE
Kreitman, RJ
Lita, E
Conlon, K
Wharfe, G
Waldmann, TA
Kaushal, A
AF Simone, Charles B., II
Morris, John C.
Stewart, Donn M.
Urquhart, Nicole E.
Janik, John E.
Kreitman, Robert J.
Lita, Elena
Conlon, Kevin
Wharfe, Gilian
Waldmann, Thomas A.
Kaushal, Aradhana
TI Radiation therapy for the management of patients with HTLV-1-associated
adult T-cell leukemia/lymphoma
SO BLOOD
LA English
DT Article
ID LEUKEMIA-LYMPHOMA
AB Human T-cell leukemia virus type 1-associated adult T-cell leukemia/lymphoma (ATL) typically has survivals measured in months with chemotherapy. One prior published series (1983-1991) assessed local radiotherapy for ATL. Ten consecutive patients with pathologically confirmed ATL treated with radiotherapy were reviewed. Subtypes included acute (n = 7), smoldering (n = 2), and lymphomatous (n = 1). Patients received an average of 2.5 systemic therapy regimens before radiotherapy. Twenty lesions (cutaneous = 10, nodal = 8, extranodal = 2) were treated to a mean of 35.4 Gy/2-3 Gy (range, 12-60 Gy). At 9.0-month mean follow-up (range, 0.1-42.0 months), all lesions symptomatically and radiographically responded, with in-field complete responses in 40.0% (nodal 37.5% vs cutaneous 50.0%; P = .62). No patient experienced in-field progression. Nine patients developed new/progressive out-of-field disease. Median survival was 17.0 months (3-year survival, 30.0%). No Radiation Therapy Oncology Group acute grade >= 3 or any late toxicity was noted. This report is the first to use modern radiotherapy techniques and finds effective local control across ATL subtypes. Radiotherapy should be considered for symptomatic local progression of ATL. (Blood. 2012;120(9):1816-1819)
C1 [Simone, Charles B., II; Kaushal, Aradhana] NCI, NIH, Radiat Oncol Branch, Bethesda, MD 20892 USA.
[Simone, Charles B., II] Hosp Univ Penn, Dept Radiat Oncol, Philadelphia, PA 19104 USA.
[Morris, John C.] Univ Cincinnati, Div Hematol Oncol, Cincinnati, OH USA.
[Morris, John C.; Stewart, Donn M.; Janik, John E.; Waldmann, Thomas A.] NCI, Metab Branch, NIH, Bethesda, MD 20892 USA.
[Urquhart, Nicole E.; Wharfe, Gilian] Univ W Indies, Dept Pathol, Jamaica, NY USA.
[Kreitman, Robert J.] NCI, Clin Immunotherapy Sect, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
[Conlon, Kevin] NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA.
RP Kaushal, A (reprint author), NCI, NIH, Radiat Oncol Branch, Bldg 10,CRC Rm B2-3561,10 Ctr Dr,MSC 1682, Bethesda, MD 20892 USA.
EM kaushala@mail.nih.gov
FU Intramural Research Program of the National Institutes of Health,
National Cancer Institute, Center for Cancer Research
FX This study is supported, in part, by the Intramural Research Program of
the National Institutes of Health, National Cancer Institute, Center for
Cancer Research.
NR 17
TC 4
Z9 4
U1 1
U2 2
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD AUG 30
PY 2012
VL 120
IS 9
BP 1816
EP 1819
DI 10.1182/blood-2012-01-401349
PG 4
WC Hematology
SC Hematology
GA 009FM
UT WOS:000309011200015
PM 22730536
ER
PT J
AU Zhao, M
Ross, JT
Itkin, T
Perry, JM
Venkatraman, A
Haug, JS
Hembree, MJ
Deng, CX
Lapidot, T
He, XC
Li, LH
AF Zhao, Meng
Ross, Jason T.
Itkin, Tomer
Perry, John M.
Venkatraman, Aparna
Haug, Jeffrey S.
Hembree, Mark J.
Deng, Chu-Xia
Lapidot, Tsvee
He, Xi C.
Li, Linheng
TI FGF signaling facilitates postinjury recovery of mouse hematopoietic
system
SO BLOOD
LA English
DT Article
ID COLONY-STIMULATING FACTOR; BONE-MARROW NICHE; STEM-CELL NICHE;
GROWTH-FACTOR-I; NF-KAPPA-B; PROGENITOR CELLS; RAPID MOBILIZATION;
STROMAL CELLS; SELF-RENEWAL; MICE
AB Previous studies have shown that fibroblast growth factor (FGF) signaling promotes hematopoietic stem and progenitor cell (HSPC) expansion in vitro. However, it is unknown whether FGF promotes HSPC expansion in vivo. Here we examined FGF receptor 1 (FGFR1) expression and investigated its in vivo function in HSPCs. Conditional knockout (CKO) of Fgfr1 did not affect phenotypical number of HSPCs and homeostatic hematopoiesis, but led to a reduced engraftment only in the secondary transplantation. When treated with 5-fluorouracil (5FU), the Fgfr1 CKO mice showed defects in both proliferation and subsequent mobilization of HSPCs. We identified mega-karyocytes (Mks) as a major resource for FGF production, and further discovered a novel mechanism by which Mks underwent FGF-FGFR signaling dependent expansion to accelerate rapid FGF production under stress. Within HSPCs, we observed an up-regulation of nuclear factor kappa B and CXCR4, a receptor for the chemoattractant SDF-1, in response to bone marrow damage only in control but not in Fgfr1 CKO model, accounting for the corresponding defects in proliferation and migration of HSPCs. This study provides the first in vivo evidence that FGF signaling facilitates postinjury recovery of the mouse hematopoietic system by promoting proliferation and facilitating mobilization of HSPCs. (Blood. 2012; 120(9):1831-1842)
C1 [Zhao, Meng; Ross, Jason T.; Perry, John M.; Venkatraman, Aparna; Haug, Jeffrey S.; Hembree, Mark J.; He, Xi C.; Li, Linheng] Stowers Inst Med Res, Kansas City, MO 64110 USA.
[Ross, Jason T.; Li, Linheng] Univ Kansas, Med Ctr, Dept Pathol & Lab Med, Kansas City, KS 66103 USA.
[Itkin, Tomer; Lapidot, Tsvee] Weizmann Inst Sci, Dept Immunol, IL-76100 Rehovot, Israel.
[Venkatraman, Aparna] Christian Med Coll & Hosp, Ctr Stem Cell Res, Vellore, Tamil Nadu, India.
[Deng, Chu-Xia] NIDDKD, NIH, Bethesda, MD 20892 USA.
RP Li, LH (reprint author), Stowers Inst Med Res, 1000 E 50th St, Kansas City, MO 64110 USA.
EM lil@stowers.org
RI Lapidot, Tsvee/A-1812-2010; deng, chuxia/N-6713-2016
FU Stowers Institute for Medical Research; Department of Biotechnology,
Ministry of S&T, Government of India
FX This work was funded by the Stowers Institute for Medical Research.
J.M.P. is a Fellow of the Leukemia & Lymphoma Society. A.V. is a
recipient of an overseas associateship from Department of Biotechnology,
Ministry of S&T, Government of India.
NR 49
TC 27
Z9 27
U1 1
U2 4
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD AUG 30
PY 2012
VL 120
IS 9
BP 1831
EP 1842
DI 10.1182/blood-2011-11-393991
PG 12
WC Hematology
SC Hematology
GA 009FM
UT WOS:000309011200017
PM 22802336
ER
PT J
AU Bedognetti, D
Ansaldi, F
Zanardi, E
Durando, P
Sertoli, MR
Massucco, C
Balleari, E
Racchi, O
Zoppoli, G
Orsi, A
Alicino, C
Icardi, G
Marincola, FM
Zupo, S
Ferrarini, M
De Maria, A
AF Bedognetti, Davide
Ansaldi, Filippo
Zanardi, Elisa
Durando, Paolo
Sertoli, Mario Roberto
Massucco, Carlotta
Balleari, Enrico
Racchi, Omar
Zoppoli, Gabriele
Orsi, Andrea
Alicino, Cristiano
Icardi, Giancarlo
Marincola, Francesco M.
Zupo, Simonetta
Ferrarini, Manlio
De Maria, Andrea
TI Seasonal and pandemic (A/H1N1 2009) MF-59-adjuvanted influenza vaccines
in complete remission non- Hodgkin lymphoma patients previously treated
with rituximab containing regimens
SO BLOOD
LA English
DT Letter
ID MEMORY B-CELLS
C1 [Bedognetti, Davide; Marincola, Francesco M.] NIH, Infect Dis & Immunogenet Sect, Dept Transfus Med, Ctr Clin,FOCIS Ctr Excellence, Bethesda, MD 20892 USA.
[Bedognetti, Davide] NIH, Trans NIH Ctr Human Immunol CHI, Bethesda, MD 20892 USA.
[Bedognetti, Davide; Sertoli, Mario Roberto; Balleari, Enrico; Zoppoli, Gabriele; Ferrarini, Manlio] Univ Genoa, Dipartimento Med Interna, Genoa, Italy.
[Bedognetti, Davide] IST Ist Nazl Ric Cancro, IRCCS Azienda Osped Univ San Martino, Azienda Osped Univ, SC Oncol Med B,IRCCS, Genoa, Italy.
[Ansaldi, Filippo; Durando, Paolo; Orsi, Andrea; Alicino, Cristiano; Icardi, Giancarlo; De Maria, Andrea] Univ Genoa, Dipartimento Sci Salute, Genoa, Italy.
[Ansaldi, Filippo; Durando, Paolo; Orsi, Andrea; Alicino, Cristiano; Icardi, Giancarlo] IST Ist Nazl Ric Cancro, IRCCS Azienda Osped Univ San Martino, UO Igiene, Genoa, Italy.
[Massucco, Carlotta; Zupo, Simonetta] IST Ist Nazl Ric Cancro, IRCCS Azienda Osped Univ San Martino, SS Diagnost Mol, Genoa, Italy.
[Racchi, Omar] Osped Villa Scassi, SS Oncol & Ematol, Genoa, Italy.
[Marincola, Francesco M.] NIH, Trans NIH CHI, Bethesda, MD 20892 USA.
[Ferrarini, Manlio] IST Ist Nazl Ric Cancro, IRCCS Azienda Osped Univ San Martino, SC Oncol Med C, Genoa, Italy.
[De Maria, Andrea] IST Ist Nazl Ric Cancro, IRCCS Azienda Osped Univ San Martino, SS Infettivol, Genoa, Italy.
RP Bedognetti, D (reprint author), NIH, Infect Dis & Immunogenet Sect, Dept Transfus Med, Ctr Clin,FOCIS Ctr Excellence, 10 Ctr Dr,Rm 1N224, Bethesda, MD 20892 USA.
EM davide.bedognetti@nih.gov; de-maria@unige.it
RI Zoppoli, Gabriele/B-6935-2016; Alicino, Cristiano/J-5325-2016; Balleari,
Enrico/R-3119-2016;
OI Zoppoli, Gabriele/0000-0003-3890-5588; Alicino,
Cristiano/0000-0002-6473-9870; Balleari, Enrico/0000-0003-2186-8012;
Bedognetti, Davide/0000-0002-5857-773X; Ferrarini,
Manlio/0000-0002-6154-2570
NR 6
TC 2
Z9 2
U1 1
U2 2
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD AUG 30
PY 2012
VL 120
IS 9
BP 1954
EP 1957
DI 10.1182/blood-2012-06-438689
PG 6
WC Hematology
SC Hematology
GA 009FM
UT WOS:000309011200030
PM 22936740
ER
PT J
AU Bae, HT
Baldwin, CT
Sebastiani, P
Telen, MJ
Ashley-Koch, A
Garrett, M
Hooper, WC
Bean, CJ
DeBaun, MR
Arking, DE
Bhatnagar, P
Casella, JF
Keefer, JR
Barron-Casella, E
Gordeuk, V
Kato, GJ
Minniti, C
Taylor, J
Campbell, A
Luchtman-Jones, L
Hoppe, C
Gladwin, MT
Zhang, YZ
Steinberg, MH
AF Bae, Harold T.
Baldwin, Clinton T.
Sebastiani, Paola
Telen, Marilyn J.
Ashley-Koch, Allison
Garrett, Melanie
Hooper, W. Craig
Bean, Christopher J.
DeBaun, Michael R.
Arking, Dan E.
Bhatnagar, Pallav
Casella, James F.
Keefer, Jeffrey Renn
Barron-Casella, Emily
Gordeuk, Victor
Kato, Gregory J.
Minniti, Caterina
Taylor, James
Campbell, Andrew
Luchtman-Jones, Lori
Hoppe, Carolyn
Gladwin, Mark T.
Zhang, Yingze
Steinberg, Martin H.
TI Meta-analysis of 2040 sickle cell anemia patients: BCL11A and HBS1L-MYB
are the major modifiers of HbF in African Americans
SO BLOOD
LA English
DT Letter
ID GENOME-WIDE ASSOCIATION; REGULATORY REGION; FETAL-HEMOGLOBIN; DISEASE
C1 [Steinberg, Martin H.] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA.
[Bae, Harold T.; Sebastiani, Paola] Boston Univ, Sch Publ Hlth, Boston, MA 02118 USA.
[Telen, Marilyn J.; Ashley-Koch, Allison; Garrett, Melanie] Duke Univ, Sch Med, Durham, NC USA.
[Hooper, W. Craig; Bean, Christopher J.] Ctr Dis Control & Prevent, Atlanta, GA USA.
[DeBaun, Michael R.] Vanderbilt Univ, Sch Med, Nashville, TN 37212 USA.
[Arking, Dan E.; Bhatnagar, Pallav; Casella, James F.; Keefer, Jeffrey Renn; Barron-Casella, Emily] Johns Hopkins Univ, Sch Med, Baltimore, MD USA.
[Gordeuk, Victor] Univ Illinois, Chicago, IL USA.
[Kato, Gregory J.; Minniti, Caterina; Taylor, James] NHLBI, NIH, Bethesda, MD 20892 USA.
[Campbell, Andrew] Univ Michigan, Sch Med, Ann Arbor, MI USA.
[Luchtman-Jones, Lori] Childrens Natl Med Ctr, Washington, DC 20010 USA.
[Hoppe, Carolyn] Childrens Hosp, Res Ctr Oakland, Oakland, CA 94609 USA.
[Gladwin, Mark T.; Zhang, Yingze] Univ Pittsburgh, Pittsburgh, PA USA.
RP Steinberg, MH (reprint author), Boston Univ, Sch Med, Dept Med, 72 E Concord St, Boston, MA 02118 USA.
EM mhsteinb@bu.edu
RI Bhatnagar, Pallav/A-1280-2013; Kato, Gregory/I-7615-2014;
OI Kato, Gregory/0000-0003-4465-3217; Steinberg,
Martin/0000-0001-8800-8020; sebastiani, paola/0000-0001-6419-1545;
Ashley-Koch, Allison/0000-0001-5409-9155; Taylor,
James/0000-0002-4421-1809
FU Intramural NIH HHS [ZIA HL005116-06]; NCRR NIH HHS [2M01 RR10284-10];
NHLBI NIH HHS [HL68959, 2R25 HL003679-8, HL079915, R01 HL079912, R01
HL87681, RC2 HL101212, U54HL090515]; NINDS NIH HHS [5-U01-NS042804-07];
PHS HHS [HHSN268200782096C]
NR 7
TC 28
Z9 29
U1 1
U2 4
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD AUG 30
PY 2012
VL 120
IS 9
BP 1961
EP 1962
DI 10.1182/blood-2012-06-432849
PG 2
WC Hematology
SC Hematology
GA 009FM
UT WOS:000309011200033
PM 22936743
ER
PT J
AU Raafat, A
Strizzi, L
Lashin, K
Ginsburg, E
McCurdy, D
Salomon, D
Smith, GH
Medina, D
Callahan, R
AF Raafat, Ahmed
Strizzi, Luigi
Lashin, Karim
Ginsburg, Erika
McCurdy, David
Salomon, David
Smith, Gilbert H.
Medina, Daniel
Callahan, Robert
TI Effects of Age and Parity on Mammary Gland Lesions and Progenitor Cells
in the FVB/N-RC Mice
SO PLOS ONE
LA English
DT Article
ID RECEPTOR-ALPHA EXPRESSION; BREAST-CANCER RISK; EPITHELIAL-CELLS;
STEM-CELLS; MOUSE; GROWTH; HYPERPLASIA; PREGNANCY; HORMONE
AB The FVB/N mouse strain is extensively used in the development of animal models for breast cancer research. Recently it has been reported that the aging FVB/N mice develop spontaneous mammary lesions and tumors accompanied with abnormalities in the pituitary glands. These observations have a great impact on the mouse models of human breast cancer. We have developed a population of inbred FVB/N mice (designated FVB/N-RC) that have been genetically isolated for 20 years. To study the effects of age and parity on abnormalities of the mammary glands of FVB/N-RC mice, twenty-five nulliparous and multiparous (3-4 pregnancies) females were euthanized at 16-22 months of age. Examination of the mammary glands did not reveal macroscopic evidence of mammary gland tumors in either aged-nulliparous or multiparous FVB/N-RC mice (0/25). However, histological analysis of the mammary glands showed rare focal nodules of squamous changes in 2 of the aged multiparous mice. Mammary gland hyperplasia was detected in 8% and 71% of the aged-nulliparous and aged-multiparous mice, respectively. Epithelial contents and serum levels of triiodothyronine were significantly higher in the experimental groups than the 14-wk-old control mice. Immuno-histochemical staining of the pituitary gland pars distalis showed no difference in prolactin staining between the control and the aged mice. Tissue transplant and dilution studies showed no effect of age and/or parity on the ability of putative progenitor cells present among the injected mammary cells to repopulate a cleared fat pad and develop a full mammary gland outgrowth. This FVB/N-RC mouse substrain is suitable to develop mouse models for breast cancer.
C1 [Raafat, Ahmed; Lashin, Karim; McCurdy, David; Smith, Gilbert H.; Callahan, Robert] NCI, Cell & Canc Biol Branch, NIH, Bethesda, MD 20892 USA.
[Strizzi, Luigi] Northwestern Univ, Feinberg Sch Med, Childrens Mem Res Ctr, Robert H Lurie Comprehens Canc Ctr, Chicago, IL USA.
[Ginsburg, Erika] NCI, Off Director, NIH, Bethesda, MD 20892 USA.
[Salomon, David] NCI, Lab Canc Prevent, NIH, Bethesda, MD 20892 USA.
[Medina, Daniel] Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA.
RP Raafat, A (reprint author), NCI, Cell & Canc Biol Branch, NIH, Bethesda, MD 20892 USA.
EM rc54d@nih.gov
FU NCI's Center for Cancer Research Intramural Research Program
FX The NCI's Center for Cancer Research Intramural Research Program funded
this work. The funder had no role in study design, data collection and
analysis, decision to publish, or preparation of the manuscript.
NR 26
TC 12
Z9 12
U1 0
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 30
PY 2012
VL 7
IS 8
AR e43624
DI 10.1371/journal.pone.0043624
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 997ZH
UT WOS:000308206500018
PM 22952723
ER
PT J
AU Smith, DB
Okur, A
Brooks, BR
AF Smith, Daniel B.
Okur, Asim
Brooks, Bernard R.
TI MDMS: Molecular dynamics meta-simulator for evaluating exchange type
sampling methods
SO CHEMICAL PHYSICS LETTERS
LA English
DT Article
ID REPLICA-EXCHANGE; ENERGY LANDSCAPE; STRUCTURE RESERVOIR; EXPLICIT WATER;
BETA-HAIRPIN; SYSTEMS; CONVERGENCE; ALGORITHM; MODEL
AB Replica exchange methods have become popular tools to explore conformational space for small proteins. For larger biological systems, even with enhanced sampling methods, exploring the free energy landscape remains computationally challenging. This problem has led to the development of many improved replica exchange methods. Unfortunately, testing these methods remains expensive. We propose a molecular dynamics meta-simulator (MDMS) based on transition state theory to simulate a replica exchange simulation, eliminating the need to run explicit dynamics between exchange attempts. MDMS simulations allow for rapid testing of new replica exchange based methods, greatly reducing the amount of time needed for new method development. Published by Elsevier B.V.
C1 [Smith, Daniel B.] Univ Pittsburgh, Dept Math, Pittsburgh, PA 15260 USA.
[Smith, Daniel B.; Okur, Asim; Brooks, Bernard R.] NHLBI, NIH, Bethesda, MD 20892 USA.
RP Smith, DB (reprint author), Univ Pittsburgh, Dept Math, Pittsburgh, PA 15260 USA.
EM smithdb3@mail.nih.gov
FU Intramural NIH HHS [Z01 HL001051-11, Z99 HL999999]
NR 30
TC 5
Z9 5
U1 0
U2 3
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0009-2614
J9 CHEM PHYS LETT
JI Chem. Phys. Lett.
PD AUG 30
PY 2012
VL 545
BP 118
EP 124
DI 10.1016/j.cplett.2012.07.015
PG 7
WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical
SC Chemistry; Physics
GA 997WW
UT WOS:000308199600022
PM 23087450
ER
PT J
AU Diesner, SC
Olivera, A
Dillahunt, S
Schultz, C
Watzlawek, T
Forster-Waldl, E
Pollak, A
Jensen-Jarolim, E
Untersmayr, E
Rivera, J
AF Diesner, Susanne C.
Olivera, Ana
Dillahunt, Sandra
Schultz, Cornelia
Watzlawek, Thomas
Foerster-Waldl, Elisabeth
Pollak, Arnold
Jensen-Jarolim, Erika
Untersmayr, Eva
Rivera, Juan
TI Sphingosine-kinase 1 and 2 contribute to oral sensitization and effector
phase in a mouse model of food allergy (vol 141, pg 210, 2012)
SO IMMUNOLOGY LETTERS
LA English
DT Correction
C1 [Diesner, Susanne C.; Schultz, Cornelia; Watzlawek, Thomas; Jensen-Jarolim, Erika; Untersmayr, Eva] Med Univ Vienna, Dept Pathophysiol & Allergy Res, Ctr Pathophysiol Infectiol & Immunol, A-1090 Vienna, Austria.
[Diesner, Susanne C.; Foerster-Waldl, Elisabeth; Pollak, Arnold] Med Univ Vienna, Dept Pediat & Adolescent Med, A-1090 Vienna, Austria.
[Diesner, Susanne C.; Olivera, Ana; Dillahunt, Sandra; Rivera, Juan] NIAMS, Immunogenet Mol Lab, NIH, Bethesda, MD 20892 USA.
[Jensen-Jarolim, Erika] Univ Vienna, Messerli Inst, Med Univ Vienna, A-1090 Vienna, Austria.
[Jensen-Jarolim, Erika] Vet Univ Vienna, A-1090 Vienna, Austria.
RP Untersmayr, E (reprint author), Med Univ Vienna, Dept Pathophysiol & Allergy Res, Ctr Pathophysiol Infectiol & Immunol, Waehringer Guertel 18-20,E3Q, A-1090 Vienna, Austria.
EM eva.untersmayr@meduniwien.ac.at; juanrivera@nih.gov
NR 1
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0165-2478
J9 IMMUNOL LETT
JI Immunol. Lett.
PD AUG 30
PY 2012
VL 146
IS 1-2
BP 79
EP 79
DI 10.1016/j.imlet.2012.04.016
PG 1
WC Immunology
SC Immunology
GA 988ZO
UT WOS:000307530200012
ER
PT J
AU Tsai, PT
Hull, C
Chu, YX
Greene-Colozzi, E
Sadowski, AR
Leech, JM
Steinberg, J
Crawley, JN
Regehr, WG
Sahin, M
AF Tsai, Peter T.
Hull, Court
Chu, YunXiang
Greene-Colozzi, Emily
Sadowski, Abbey R.
Leech, Jarrett M.
Steinberg, Jason
Crawley, Jacqueline N.
Regehr, Wade G.
Sahin, Mustafa
TI Autistic-like behaviour and cerebellar dysfunction in Purkinje cell Tsc1
mutant mice
SO NATURE
LA English
DT Article
ID TUBEROUS SCLEROSIS COMPLEX; MOUSE MODEL; ULTRASONIC VOCALIZATIONS;
BRAIN; DISORDERS; CHILDREN; SURVIVAL; MTORC1
AB Autism spectrum disorders (ASDs) are highly prevalent neurodevelopmental disorders(1), but the underlying pathogenesis remains poorly understood. Recent studies have implicated the cerebellum in these disorders, with post-mortem studies in ASD patients showing cerebellar Purkinje cell (PC) loss(2,3), and isolated cerebellar injury has been associated with a higher incidence of ASDs(4). However, the extent of cerebellar contribution to the pathogenesis of ASDs remains unclear. Tuberous sclerosis complex (TSC) is a genetic disorder with high rates of comorbid ASDs(5) that result from mutation of either TSC1 or TSC2, whose protein products dimerize and negatively regulate mammalian target of rapamycin (mTOR) signalling. TSC is an intriguing model to investigate the cerebellar contribution to the underlying pathogenesis of ASDs, as recent studies in TSC patients demonstrate cerebellar pathology(6) and correlate cerebellar pathology with increased ASD symptomatology(7,8). Functional imaging also shows that TSC patients with ASDs display hypermetabolism in deep cerebellar structures, compared to TSC patients without ASDs(9). However, the roles of Tsc1 and the sequelae of Tsc1 dysfunction in the cerebellum have not been investigated so far. Here we show that both heterozygous and homozygous loss of Tsc1 in mouse cerebellar PCs results in autistic-like behaviours, including abnormal social interaction, repetitive behaviour and vocalizations, in addition to decreased PC excitability. Treatment of mutant mice with the mTOR inhibitor, rapamycin, prevented the pathological and behavioural deficits. These findings demonstrate new roles for Tsc1 in PC function and define a molecular basis for a cerebellar contribution to cognitive disorders such as autism.
C1 [Tsai, Peter T.; Greene-Colozzi, Emily; Sadowski, Abbey R.; Leech, Jarrett M.; Steinberg, Jason; Sahin, Mustafa] Harvard Univ, Sch Med, Boston Childrens Hosp, FM Kirby Neurobiol Ctr,Dept Neurol, Boston, MA 02115 USA.
[Hull, Court; Chu, YunXiang; Regehr, Wade G.] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA.
[Crawley, Jacqueline N.] NIMH, Lab Behav Neurosci, Intramural Res Program, Bethesda, MD 20892 USA.
RP Sahin, M (reprint author), Harvard Univ, Sch Med, Boston Childrens Hosp, FM Kirby Neurobiol Ctr,Dept Neurol, Boston, MA 02115 USA.
EM peter.tsai@childrens.harvard.edu; mustafa.sahin@childrens.harvard.edu
OI Hull, Court/0000-0002-0360-8367
FU Developmental Neurology Training grant [T32 NS007473]; American Academy
of Neurology; Nancy Lurie Marks Family Foundation; National Institutes
of Health (NIH) [R01 NS58956]; John Merck Scholars Fund; Autism Speaks;
Boston Children's Hospital Translational Research Program; Manton Center
for Orphan Disease Research; Boston Children's Hospital Intellectual and
Developmental Disabilities Research Center [P30 HD18655]; Intramural
Research Program, National Institute of Mental Health; NIH
[R01NS032405]; Simons Foundation [SFARI 232304]; Howard Hughes Medical
Institute Medical Research Fellowship
FX We thank G. Corfas, M. Fagiolini, P. Rosenberg, S. Goldman and the
Neurodevelopmental Behavioral Core of Boston Children's Hospital for
assistance with behavioural experiments. We are grateful to C. Walsh, L.
Benowitz and members of the Sahin laboratory for critical reading of the
manuscript, and to M. Gregas for advice regarding statistical analysis.
P. T. T. received support from the Developmental Neurology Training
grant (T32 NS007473), American Academy of Neurology, and the Nancy Lurie
Marks Family Foundation. This work and M. S. are supported in part by
the National Institutes of Health (NIH; grant R01 NS58956), the John
Merck Scholars Fund, Autism Speaks, the Nancy Lurie Marks Family
Foundation, Boston Children's Hospital Translational Research Program,
Manton Center for Orphan Disease Research and Boston Children's Hospital
Intellectual and Developmental Disabilities Research Center (grant P30
HD18655). J.N.C. is supported by the Intramural Research Program,
National Institute of Mental Health. W. G. R. is supported by the NIH
(grant R01NS032405) and the Simons Foundation (grant SFARI 232304).
Y.X.C. is supported by the Howard Hughes Medical Institute Medical
Research Fellowship.
NR 38
TC 215
Z9 219
U1 5
U2 51
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
J9 NATURE
JI Nature
PD AUG 30
PY 2012
VL 488
IS 7413
BP 647
EP +
DI 10.1038/nature11310
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 996NC
UT WOS:000308095100054
PM 22763451
ER
PT J
AU Westreich, D
Cole, SR
Schisterman, EF
Platt, RW
AF Westreich, Daniel
Cole, Stephen R.
Schisterman, Enrique F.
Platt, Robert W.
TI A simulation study of finite-sample properties of marginal structural
Cox proportional hazards models
SO STATISTICS IN MEDICINE
LA English
DT Article
DE bias; causal inference; marginal structural models; Monte Carlo study
ID ACTIVE ANTIRETROVIRAL THERAPY; HUMAN-IMMUNODEFICIENCY-VIRUS; INVERSE
PROBABILITY WEIGHTS; ADJUSTED SURVIVAL CURVES; CARDIOVASCULAR MORTALITY;
CAUSAL INFERENCE; CONTROLLED-TRIAL; HIV-INFECTION; TUBERCULOSIS; DISEASE
AB Motivated by a previously published study of HIV treatment, we simulated data subject to time-varying confounding affected by prior treatment to examine some finite-sample properties of marginal structural Cox proportional hazards models. We compared (a)?unadjusted, (b)?regression-adjusted, (c)?unstabilized, and (d)?stabilized marginal structural (inverse probability-of-treatment [IPT] weighted) model estimators of effect in terms of bias, standard error, root mean squared error (MSE), and 95% confidence limit coverage over a range of research scenarios, including relatively small sample sizes and 10 study assessments. In the base-case scenario resembling the motivating example, where the true hazard ratio was 0.5, both IPT-weighted analyses were unbiased, whereas crude and adjusted analyses showed substantial bias towards and across the null. Stabilized IPT-weighted analyses remained unbiased across a range of scenarios, including relatively small sample size; however, the standard error was generally smaller in crude and adjusted models. In many cases, unstabilized weighted analysis showed a substantial increase in standard error compared with other approaches. Root MSE was smallest in the IPT-weighted analyses for the base-case scenario. In situations where time-varying confounding affected by prior treatment was absent, IPT-weighted analyses were less precise and therefore had greater root MSE compared with adjusted analyses. The 95% confidence limit coverage was close to nominal for all stabilized IPT-weighted but poor in crude, adjusted, and unstabilized IPT-weighted analysis. Under realistic scenarios, marginal structural Cox proportional hazards models performed according to expectations based on?large-sample theory and provided accurate estimates of the hazard ratio. Copyright (C) 2012 John Wiley & Sons, Ltd.
C1 [Westreich, Daniel] Duke Univ, Dept Obstet & Gynecol, Durham, NC 27710 USA.
[Westreich, Daniel] Duke Univ, Duke Global Hlth Inst, Durham, NC USA.
[Cole, Stephen R.] UNC Gillings Sch Global Publ Hlth, Dept Epidemiol, Chapel Hill, NC USA.
[Schisterman, Enrique F.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Bethesda, MD USA.
[Platt, Robert W.] McGill Univ, Dept Epidemiol Biostat & Occupat Hlth, Montreal, PQ, Canada.
RP Westreich, D (reprint author), Duke Univ, Dept Obstet & Gynecol, Durham, NC 27710 USA.
EM daniel.westreich@duke.edu
RI Platt, Robert/G-5847-2012;
OI Platt, Robert/0000-0002-5981-8443; Schisterman,
Enrique/0000-0003-3757-641X
FU National Institutes of Health, National Institute of Allergy and
Infectious Disease [T32-AI-07001, R01-AA-01759]; National Institutes of
Health the Eunice Kennedy Shriver National Institute of Child Health and
Human Development [K99-HD-06-3961, 4R00-HD-06-3961-02];
Chercheur-Boursier award; Fonds de la Recherche en Sante' du Quebec;
National Institute of Allergy and Infectious Diseases [UO1-AI-35004,
UO1-AI-31834, UO1-AI-34994, UO1-AI-34989, UO1-AI-34993, UO1-AI-42590];
National Institute of Child Health and Human Development [UO1-HD32632];
National Cancer Institute; National Institute on Drug Abuse; National
Institute on Deafness and Other Communication Disorders; National Center
for Research Resources (UCSF-CTSI) [UL1 RR024131]; National Institute of
Allergy and Infectious Diseases; National Cancer Institute
[UO1-AI-35042, UL1-RR025005, UO1-AI-35043, UO1-AI-35039, UO1-AI-35040,
UO1-AI-35041]
FX This work was supported by the National Institutes of Health, National
Institute of Allergy and Infectious Disease [grant number T32-AI-07001
to D. W.; grant number R01-AA-01759 to S. R. C.]; the National
Institutes of Health the Eunice Kennedy Shriver National Institute of
Child Health and Human Development [Intramural Research Program to E. F.
S.; grant numbers K99-HD-06-3961 and 4R00-HD-06-3961-02 to D. W.]; and
the Chercheur-Boursier award and by core support to the Montreal
Children's Hospital Research Institute, from the Fonds de la Recherche
en Sante' du Quebec to [R. W. P.].; Data in this manuscript were
collected by the Women's Interagency HIV Study (WIHS) Collaborative
Study Group with centers (Principal Investigators) at New York
City/Bronx Consortium (Kathryn Anastos); Brooklyn, NY (Howard Minkoff);
Washington, DC, Metropolitan Consortium (Mary Young); The Connie Wofsy
Study Consortium of Northern California (Ruth Greenblatt); Los Angeles
County/Southern California Consortium (Alexandra Levine); Chicago
Consortium (Mardge Cohen); Data Coordinating Center (Stephen Gange). The
WIHS is funded by the National Institute of Allergy and Infectious
Diseases (UO1-AI-35004, UO1-AI-31834, UO1-AI-34994, UO1-AI-34989,
UO1-AI-34993, and UO1-AI-42590) and by the National Institute of Child
Health and Human Development (UO1-HD32632). The study is co-funded by
the National Cancer Institute, the National Institute on Drug Abuse, and
the National Institute on Deafness and Other Communication Disorders.
Funding is also provided by the National Center for Research Resources
(UCSF-CTSI Grant Number UL1 RR024131). The contents of this publication
are solely the responsibility of the authors and do not necessarily
represent the official views of the National Institutes of Health.; Data
in this manuscript were collected by the Multicenter AIDS Cohort Study
(MACS) with centers (Principal Investigators) at The Johns Hopkins
Bloomberg School of Public Health (Joseph B. Margolick, Lisa P.
Jacobson), Howard Brown Health Center, Feinberg School of Medicine,
Northwestern University, and Cook County Bureau of Health Services (John
P. Phair, Steven M. Wolinsky), University of California, Los Angeles
(Roger Detels), and University of Pittsburgh (Charles R. Rinaldo). The
MACS is funded by the National Institute of Allergy and Infectious
Diseases, with additional supplemental funding from the National Cancer
Institute (UO1-AI-35042, UL1-RR025005 (GCRC), UO1-AI-35043,
UO1-AI-35039, UO1-AI-35040, and UO1-AI-35041). Website is located at
http://www.statepi.jhsph.edu/macs/macs.html.
NR 42
TC 10
Z9 10
U1 1
U2 14
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 2012
VL 31
IS 19
BP 2098
EP 2109
DI 10.1002/sim.5317
PG 12
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 974XW
UT WOS:000306471900006
PM 22492660
ER
PT J
AU Wang, AR
Chandran, S
Shah, SA
Chiu, Y
Paria, BC
Aghamolla, T
Alvarez-Downing, MM
Lee, CCR
Singh, S
Li, T
Dudley, ME
Restifo, NP
Rosenberg, SA
Kammula, US
AF Wang, Anran
Chandran, Smita
Shah, Syed A.
Chiu, Yu
Paria, Biman C.
Aghamolla, Tamara
Alvarez-Downing, Melissa M.
Lee, Chyi-Chia Richard
Singh, Sanmeet
Li, Thomas
Dudley, Mark E.
Restifo, Nicholas P.
Rosenberg, Steven A.
Kammula, Udai S.
TI The Stoichiometric Production of IL-2 and IFN-gamma mRNA Defines Memory
T Cells That Can Self-Renew After Adoptive Transfer in Humans
SO SCIENCE TRANSLATIONAL MEDICINE
LA English
DT Article
ID METASTATIC MELANOMA; TRANSFER THERAPY; PROTECTIVE IMMUNITY; ANTITUMOR
IMMUNITY; CANCER REGRESSION; PERIPHERAL-BLOOD; SUPPRESSOR-CELLS;
TUMOR-REGRESSION; LYMPHOCYTES; IMMUNOTHERAPY
AB Adoptive immunotherapy using ex vivo-expanded tumor-reactive lymphocytes can mediate durable cancer regression in selected melanoma patients. Analyses of these trials have associated the in vivo engraftment ability of the transferred cells with their antitumor efficacy. Thus, there is intensive clinical interest in the prospective isolation of tumor-specific T cells that can reliably persist after transfer. Animal studies have suggested that central memory CD8(+) T cells (T-CM) have divergent capabilities including effector differentiation to target antigen and stem cell-like self-renewal that enable long-term survival after adoptive transfer. We sought to isolate human melanoma-specific T-CM to define their in vivo fate and function after autologous therapeutic transfer to metastatic patients. To facilitate the high-throughput identification of these rare cells from patients, we report that T-CM have a defined stoichiometric production of interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) mRNA after antigen stimulation. Melanoma-specific T cells screened for high relative IL-2 production had a TCM phenotype and superior in vitro proliferative capacity compared to cells with low IL-2 production. To investigate in vivo effector function and self-renewal capability, we allowed melanoma-specific T-CM to undergo in vitro expansion and differentiation into lytic effector clones and then adoptively transferred them back into their hosts. These clones targeted skin melanocytes in all five patients and persisted long term and reacquired parental T-CM attributes in four patients after transfer. These findings demonstrate the favorable engraftment fitness for human T-CM-derived clones, but further efforts to improve their antitumor efficacy are still necessary.
C1 [Wang, Anran; Chandran, Smita; Shah, Syed A.; Chiu, Yu; Paria, Biman C.; Aghamolla, Tamara; Alvarez-Downing, Melissa M.; Lee, Chyi-Chia Richard; Singh, Sanmeet; Li, Thomas; Dudley, Mark E.; Restifo, Nicholas P.; Rosenberg, Steven A.; Kammula, Udai S.] NCI, Ctr Canc Res, NIH, Bethesda, MD 20817 USA.
RP Kammula, US (reprint author), NCI, Ctr Canc Res, NIH, Bethesda, MD 20817 USA.
EM udai_kammula@nih.gov
RI Restifo, Nicholas/A-5713-2008; Lee, Chyi-Chia/I-1938-2013;
OI Lee, Chyi-Chia/0000-0002-5306-7781; Restifo, Nicholas
P./0000-0003-4229-4580
FU Intramural Research Program of the NIH, NCI, Center for Cancer Research
FX We thank the Surgery Branch cell production facility and the
immunotherapy clinical and support staff for their contributions.
Funding: This research was supported by the Intramural Research Program
of the NIH, NCI, Center for Cancer Research.
NR 40
TC 23
Z9 23
U1 0
U2 8
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 1946-6234
J9 SCI TRANSL MED
JI Sci. Transl. Med.
PD AUG 29
PY 2012
VL 4
IS 149
AR 149ra120
DI 10.1126/scitranslmed.3004306
PG 13
WC Cell Biology; Medicine, Research & Experimental
SC Cell Biology; Research & Experimental Medicine
GA 001WT
UT WOS:000308491600011
PM 22932225
ER
PT J
AU Marincola, FM
Sheikh, JI
AF Marincola, Francesco M.
Sheikh, Javaid I.
TI A road map to Translational Medicine in Qatar and a model for the world
SO JOURNAL OF TRANSLATIONAL MEDICINE
LA English
DT Review
ID CLINICAL-RESEARCH ENTERPRISE; VITAMIN-D INSUFFICIENCY;
CANCER-IMMUNOTHERAPY; BIOMEDICAL-RESEARCH; BASIC SCIENCE; OBSTACLES;
OPPORTUNITIES; SCIENTISTS; CHALLENGES; THERAPIES
AB Translational Medicine (TM) in Qatar is part of a concerted effort of the Qatari medical and scientific leadership supported by a strong political will by Qatari authorities to deliver world-class health care to Qatari residents while participating in the worldwide quest to bridge the gap between bench-to-bedside-to-community. TM programs should embrace the Qatar National vision for research to become an international hub of excellence in research and development, based on intellectual merit, contributing to global knowledge and adhering to international standards, to innovate by translating new and original ideas into useful applications, to be inclusive at the national and international level, to build and maintain a competitive and diversified economy and ultimately improve the health and well-being of the Qatar's population. Although this writing focuses on Qatar, we hope that the thoughts expressed here may be of broader use for the development of any TM program particularly in regions where an established academic community surrounded by a rich research infrastructure and/or a vibrant biotechnology enterprise is not already present.
C1 [Marincola, Francesco M.; Sheikh, Javaid I.] Qatar Fdn, Off Dean, Weill Cornell Med Coll Qatar, Doha, Qatar.
[Marincola, Francesco M.] NIH, Ctr Clin, Bethesda, MD 20892 USA.
RP Marincola, FM (reprint author), Qatar Fdn, Off Dean, Weill Cornell Med Coll Qatar, POB 24144, Doha, Qatar.
EM fmarincola@mail.cc.nih.gov
NR 70
TC 4
Z9 4
U1 1
U2 9
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1479-5876
J9 J TRANSL MED
JI J. Transl. Med.
PD AUG 29
PY 2012
VL 10
AR 177
DI 10.1186/1479-5876-10-177
PG 15
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 002OX
UT WOS:000308542600001
PM 22929646
ER
PT J
AU Civiero, L
Vancraenenbroeck, R
Belluzzi, E
Beilina, A
Lobbestael, E
Reyniers, L
Gao, FY
Micetic, I
De Maeyer, M
Bubacco, L
Baekelandt, V
Cookson, MR
Greggio, E
Taymans, JM
AF Civiero, Laura
Vancraenenbroeck, Renee
Belluzzi, Elisa
Beilina, Alexandra
Lobbestael, Evy
Reyniers, Lauran
Gao, Fangye
Micetic, Ivan
De Maeyer, Marc
Bubacco, Luigi
Baekelandt, Veerle
Cookson, Mark R.
Greggio, Elisa
Taymans, Jean-Marc
TI Biochemical Characterization of Highly Purified Leucine-Rich Repeat
Kinases 1 and 2 Demonstrates Formation of Homodimers
SO PLOS ONE
LA English
DT Article
ID DISEASE-ASSOCIATED MUTATIONS; FAMILIAL PARKINSONS-DISEASE; ROC DOMAIN;
GTP-BINDING; CYTOPLASMIC LOCALIZATION; DOMINANT PARKINSONISM;
PROTEIN-KINASES; LRRK2 MUTATION; GENE LRRK2;
LEUCINE-RICH-REPEAT-KINASE-2
AB Leucine-rich repeat kinase 1 and 2 (LRRK1 and LRRK2) are large multidomain proteins containing kinase, GTPase and multiple protein-protein interaction domains, but only mutations in LRRK2 are linked to familial Parkinson's disease (PD). Independent studies suggest that LRRK2 exists in the cell as a complex compatible with the size of a dimer. However, whether this complex is truly a homodimer or a heterologous complex formed by monomeric LRRK2 with other proteins has not been definitively proven due to the limitations in obtaining highly pure proteins suitable for structural characterization. Here, we used stable expression of LRRK1 and LRRK2 in HEK293T cell lines to produce recombinant LRRK1 and LRRK2 proteins of greater than 90% purity. Both purified LRRKs are folded, with a predominantly alpha-helical secondary structure and are capable of binding GTP with similar affinity. Furthermore, recombinant LRRK2 exhibits robust autophosphorylation activity, phosphorylation of model peptides in vitro and ATP binding. In contrast, LRRK1 does not display significant autophosphorylation activity and fails to phosphorylate LRRK2 model substrates, although it does bind ATP. Using these biochemically validated proteins, we show that LRRK1 and LRRK2 are capable of forming homodimers as shown by single-particle transmission electron microscopy and immunogold labeling. These LRRK dimers display an elongated conformation with a mean particle size of 145 angstrom and 175 angstrom respectively, which is disrupted by addition of 6M guanidinium chloride. Immunogold staining revealed double-labeled particles also in the pathological LRRK2 mutant G2019S and artificial mutants disrupting GTPase and kinase activities, suggesting that point mutations do not hinder the dimeric conformation. Overall, our findings indicate for the first time that purified and active LRRK1 and LRRK2 can form dimers in their full-length conformation.
C1 [Civiero, Laura; Belluzzi, Elisa; Micetic, Ivan; Bubacco, Luigi; Greggio, Elisa] Univ Padua, Dept Biol, Padua, Italy.
[Vancraenenbroeck, Renee; Lobbestael, Evy; Reyniers, Lauran; Gao, Fangye; Baekelandt, Veerle; Taymans, Jean-Marc] Katholieke Univ Leuven, Lab Neurobiol & Gene Therapy, Louvain, Belgium.
[Vancraenenbroeck, Renee; De Maeyer, Marc] Katholieke Univ Leuven, Lab Biomol Modelling, B-3001 Heverlee, Belgium.
[Beilina, Alexandra; Cookson, Mark R.] NIA, Cell Biol & Gene Express Unit, Neurogenet Lab, Bethesda, MD 20892 USA.
RP Civiero, L (reprint author), Univ Padua, Dept Biol, Padua, Italy.
EM elisa.greggio@unipd.it; jean-marc.taymans@med.kuleuven.be
RI Greggio, Elisa/H-6119-2013; Micetic, Ivan/A-7146-2015;
OI Greggio, Elisa/0000-0002-8172-3598; Micetic, Ivan/0000-0003-1691-8425;
Taymans, Jean-Marc/0000-0001-5503-5524; Belluzzi,
Elisa/0000-0003-1129-2574; Bubacco, Luigi/0000-0001-7927-9208
FU Michael J Fox Foundation; Rientro dei Cervelli Program (lncentivazione
alla mobilita di studiosi stranieri e italiani residenti all'estero)
from the Italian Ministry of Education, University and Research;
PRIN2008 [55YP79]; Intramural Research Program of the National
Institutes of Health, National Institute on Aging; Research Foundation -
Flanders Fonds Wetenschappelijk Onderzoek (FWO) [G.0666.09]; project
Neuro-TARGET [IWT SBO/80020]; KULeuven [OT/08/052A, IOF-KP/07/001]
FX Funding provided by the Michael J Fox Foundation; the Rientro dei
Cervelli Program (lncentivazione alla mobilita di studiosi stranieri e
italiani residenti all'estero) from the Italian Ministry of Education,
University and Research (EG); PRIN2008 (55YP79) (LB); the Intramural
Research Program of the National Institutes of Health, National
Institute on Aging; the Research Foundation - Flanders Fonds
Wetenschappelijk Onderzoek (FWO project G.0666.09, PhD fellowships to
RVC, EL and senior researcher fellowship to J-MT); the IWT SBO/80020
project Neuro-TARGET; the KULeuven (OT/08/052A and IOF-KP/07/001); and
the Fund Druwe-Eerdekens managed by the King Baudouin Foundation (J-MT).
The funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 63
TC 31
Z9 33
U1 1
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 29
PY 2012
VL 7
IS 8
AR e43472
DI 10.1371/journal.pone.0043472
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 997ZC
UT WOS:000308206000037
PM 22952686
ER
PT J
AU Wang, TG
Lee, MH
Choi, E
Pardo-Villamizar, CA
Bin Lee, S
Yang, IH
Calabresi, PA
Nath, A
AF Wang, Tongguang
Lee, Myoung-Hwa
Choi, Elliot
Pardo-Villamizar, Carlos A.
Bin Lee, Sung
Yang, In Hong
Calabresi, Peter A.
Nath, Avindra
TI Granzyme B-Induced Neurotoxicity Is Mediated via Activation of PAR-1
Receptor and Kv1.3 Channel
SO PLOS ONE
LA English
DT Article
ID PROTEIN-COUPLED RECEPTOR; LONG-TERM-MEMORY; POTASSIUM CHANNELS; T-CELLS;
HIPPOCAMPAL-NEURONS; NOTCH-1 ACTIVATION; MULTIPLE-SCLEROSIS; THERAPEUTIC
TARGET; SIGNALING PATHWAYS; CASPASE ACTIVATION
AB Increasing evidence supports a critical role of T cells in neurodegeneration associated with acute and subacute brain inflammatory disorders. Granzyme B (GrB), released by activated T cells, is a cytotoxic proteinase which may induce perforin-independent neurotoxicity. Here, we studied the mechanism of perforin-independent GrB toxicity by treating primary cultured human neuronal cells with recombinant GrB. GrBactivated the protease-activated receptor (PAR)-1 receptor on the neuronal cell surface leading to decreased intracellular cyclic AMP levels. This was followed by increased expression and translocation of the voltage gated potassium channel, Kv1.3 to the neuronal cell membrane. Similar expression of Kv1.3 was also seen in neurons of the cerebral cortex adjacent to active inflammatory lesions in patients with multiple sclerosis. Kv1.3 expression was followed by activation of Notch-1 resulting in neurotoxicity. Blocking PAR-1, Kv1.3 or Notch-1 activation using specific pharmacological inhibitors or siRNAs prevented GrB-induced neurotoxicity. Furthermore, clofazimine protected against GrB-induced neurotoxicity in rat hippocampus, in vivo. These observations indicate that GrB released from T cells induced neurotoxicity by interacting with the membrane bound Gi-coupled PAR-1 receptor and subsequently activated Kv1.3 and Notch-1. These pathways provide novel targets to treat T cell-mediated neuroinflammatory disorders. Kv1.3 is of particular interest since it is expressed on the cell surface, only under pathological circumstances, and early in the cascade of events making it an attractive therapeutic target.
C1 [Wang, Tongguang; Lee, Myoung-Hwa; Choi, Elliot; Nath, Avindra] NINDS, Sect Infect Nervous Syst, NIH, Bethesda, MD 20892 USA.
[Pardo-Villamizar, Carlos A.; Calabresi, Peter A.; Nath, Avindra] Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21218 USA.
[Bin Lee, Sung; Yang, In Hong] Johns Hopkins Univ, Dept Biomed Engn, Baltimore, MD 21218 USA.
[Yang, In Hong] Natl Univ Singapore, Singapore Inst Nanotechnol, Singapore 117548, Singapore.
RP Wang, TG (reprint author), NINDS, Sect Infect Nervous Syst, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
EM natha@ninds.nih.gov
RI Yang, In Hong/F-9125-2015
FU National Multiple Sclerosis Society; National Institutes of Health (NIH)
[NS41435]; NIH intramural funds; Project Restore-Bart Mclean Fund for
Neuroimmunology Research; Maryland Stem Cell Research Fund
FX The work was supported by grants from the National Multiple Sclerosis
Society, the National Institutes of Health (NIH) (NS41435, PAC), NIH
intramural funds, Project Restore-Bart Mclean Fund for Neuroimmunology
Research, and the Maryland Stem Cell Research Fund. The funders had no
role in study design, data collection and analysis, decision to publish,
or preparation of the manuscript.
NR 56
TC 9
Z9 9
U1 0
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 29
PY 2012
VL 7
IS 8
AR e43950
DI 10.1371/journal.pone.0043950
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 997ZC
UT WOS:000308206000062
PM 22952817
ER
PT J
AU Cavanaugh, J
Joiner, WM
Wurtz, RH
AF Cavanaugh, James
Joiner, Wilsaan M.
Wurtz, Robert H.
TI Suppressive Surrounds of Receptive Fields In Monkey Frontal Eye Field
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
ID LATERAL INTRAPARIETAL AREA; MACAQUE V1 NEURONS; VISUAL-CORTEX;
ORGANIZATION; MODULATION; RESPONSES; SIGNALS; SELECTIVITY; ATTENTION;
SACCADES
AB A critical step in determining how a neuron contributes to visual processing is determining its visual receptive field (RF). While recording from neurons in frontal eye field (FEF) of awake monkeys (Macaca mulatta), we probed the visual field with small spots of light and found excitatory RFs that decreased in strength from RF center to periphery. However, presenting stimuli with different diameters centered on the RF revealed suppressive surrounds that overlapped the previously determined excitatory RF and reduced responses by 84%, on average. Consequently, in that overlap area, stimulation produced excitation or suppression, depending on the stimulus. Strong stimulation of the RF periphery with annular stimuli allowed us to quantify this effect. A modified difference of Gaussians model that independently varied center and surround activation accounted for the nonlinear activity in the overlap area. Our results suggest that (1) the suppressive surrounds found in FEF are fundamentally the same as those in V1 except for the size and strength of excitatory and suppressive mechanisms, (2) methodically assaying suppressive surrounds in FEF is essential for correctly interpreting responses to large and/or peripheral stimuli and therefore understanding the effects of stimulus context, and (3) regulating the relative strength of the surround clearly changes neuronal responses and may therefore play a significant part in the neuronal changes resulting from visual attention and stimulus salience.
C1 [Cavanaugh, James; Joiner, Wilsaan M.; Wurtz, Robert H.] NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20982 USA.
RP Cavanaugh, J (reprint author), NEI, Sensorimotor Res Lab, NIH, Bldg 49,Room 2A50,49 Convent Dr, Bethesda, MD 20982 USA.
EM jrc@lsr.nei.nih.gov
FU National Eye Institute Intramural Research Program at the National
Institutes of Health
FX This work was supported by the National Eye Institute Intramural
Research Program at the National Institutes of Health. We are grateful
to Altah Nichols and Tom Ruffner for machine shop support.
NR 26
TC 15
Z9 15
U1 1
U2 7
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 29
PY 2012
VL 32
IS 35
BP 12284
EP 12293
DI 10.1523/JNEUROSCI.0864-12.2012
PG 10
WC Neurosciences
SC Neurosciences & Neurology
GA 998CD
UT WOS:000308213900034
PM 22933810
ER
PT J
AU Rotimi, CN
AF Rotimi, Charles N.
TI Health disparities in the genomic era: the case for diversifying ethnic
representation
SO GENOME MEDICINE
LA English
DT Editorial Material
DE Genomics; genomic medicine; health disparity; minority health; genetic
awareness; pharmacogenomics complex diseases; community outreach;
international collaboration
AB A report on the meeting 'Why we can't wait: conference to eliminate health disparities in genomic medicine', Miami, Florida, USA, 31 May to 1 June 2012.
C1 NHGRI, Ctr Res Genom & Global Hlth, NIH, Bethesda, MD 20892 USA.
RP Rotimi, CN (reprint author), NHGRI, Ctr Res Genom & Global Hlth, NIH, Bethesda, MD 20892 USA.
EM rotimic@mail.nih.gov
NR 0
TC 4
Z9 4
U1 0
U2 1
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 28
PY 2012
VL 4
AR 65
DI 10.1186/gm366
PG 3
WC Genetics & Heredity
SC Genetics & Heredity
GA 084XZ
UT WOS:000314575300001
PM 22929582
ER
PT J
AU Yoon, J
Park, HS
Damiano, DL
AF Yoon, Jungwon
Park, Hyung-Soon
Damiano, Diane Louise
TI A novel walking speed estimation scheme and its application to treadmill
control for gait rehabilitation
SO JOURNAL OF NEUROENGINEERING AND REHABILITATION
LA English
DT Article
DE Body-weight supported treadmill training; Walking velocity estimation;
Self-selected treadmill speed control; Gait analysis; Temporal-spatial
gait parameters
ID STROKE PATIENTS; LOCOMOTION INTERFACE; LOKOMAT; SYSTEM; POSTSTROKE;
KINEMATICS; FEEDBACK; INJURY; ADULTS; TRIAL
AB Background: Virtual reality (VR) technology along with treadmill training (TT) can effectively provide goal-oriented practice and promote improved motor learning in patients with neurological disorders. Moreover, the VR + TT scheme may enhance cognitive engagement for more effective gait rehabilitation and greater transfer to over ground walking. For this purpose, we developed an individualized treadmill controller with a novel speed estimation scheme using swing foot velocity, which can enable user-driven treadmill walking (UDW) to more closely simulate over ground walking (OGW) during treadmill training. OGW involves a cyclic acceleration-deceleration profile of pelvic velocity that contrasts with typical treadmill-driven walking (TDW), which constrains a person to walk at a preset constant speed. In this study, we investigated the effects of the proposed speed adaptation controller by analyzing the gait kinematics of UDW and TDW, which were compared to those of OGW at three pre-determined velocities.
Methods: Ten healthy subjects were asked to walk in each mode (TDW, UDW, and OGW) at three pre-determined speeds (0.5 m/s, 1.0 m/s, and 1.5 m/s) with real time feedback provided through visual displays. Temporal-spatial gait data and 3D pelvic kinematics were analyzed and comparisons were made between UDW on a treadmill, TDW, and OGW.
Results: The observed step length, cadence, and walk ratio defined as the ratio of stride length to cadence were not significantly different between UDW and TDW. Additionally, the average magnitude of pelvic acceleration peak values along the anterior-posterior direction for each step and the associated standard deviations (variability) were not significantly different between the two modalities. The differences between OGW and UDW and TDW were mainly in swing time and cadence, as have been reported previously. Also, step lengths between OGW and TDW were different for 0.5 m/s and 1.5 m/s gait velocities, and walk ratio between OGS and UDW was different for 1.0 m/s gait velocities.
Conclusions: Our treadmill control scheme implements similar gait biomechanics of TDW, which has been used for repetitive gait training in a small and constrained space as well as controlled and safe environments. These results reveal that users can walk as stably during UDW as TDW and employ similar strategies to maintain walking speed in both UDW and TDW. Furthermore, since UDW can allow a user to actively participate in the virtual reality (VR) applications with variable walking velocity, it can induce more cognitive activities during the training with VR, which may enhance motor learning effects.
C1 [Yoon, Jungwon; Park, Hyung-Soon; Damiano, Diane Louise] NIH, Dept Rehabil Med, Ctr Clin, Bethesda, MD 20892 USA.
[Yoon, Jungwon] Gyeongsang Natl Univ, Sch Mech Engn, Jinju, South Korea.
[Yoon, Jungwon] Gyeongsang Natl Univ, ReCAPT, Jinju, South Korea.
RP Park, HS (reprint author), NIH, Dept Rehabil Med, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA.
EM parkhs@cc.nih.gov
RI Park, Hyung-Soon/B-3334-2010; Damiano, Diane/B-3338-2010;
OI Park, Hyung-Soon/0000-0003-4274-7420; Damiano,
Diane/0000-0002-2770-5356; Yoon, Jungwon/0000-0003-1350-5334
FU NIH [90-CC-0168]; LG Yeonam foundation [NRF 2011-0031383]
FX This research was supported by NIH protocol number 90-CC-0168 and LG
Yeonam foundation Foreigner Research Professor Program & the Priority
Research Centers Program under Grant NRF 2011-0031383.
NR 44
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Z9 10
U1 1
U2 27
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1743-0003
J9 J NEUROENG REHABIL
JI J. NeuroEng. Rehabil.
PD AUG 28
PY 2012
VL 9
AR 62
DI 10.1186/1743-0003-9-62
PG 13
WC Engineering, Biomedical; Neurosciences; Rehabilitation
SC Engineering; Neurosciences & Neurology; Rehabilitation
GA 072CU
UT WOS:000313646900001
PM 22929169
ER
PT J
AU Arora, R
del Alcazar, CM
Morrisey, EE
Naiche, LA
Papaioannou, VE
AF Arora, Ripla
del Alcazar, Chelsea M.
Morrisey, Edward E.
Naiche, L. A.
Papaioannou, Virginia E.
TI Candidate Gene Approach Identifies Multiple Genes and Signaling Pathways
Downstream of Tbx4 in the Developing Allantois
SO PLOS ONE
LA English
DT Article
ID EARLY EMBRYONIC LETHALITY; BETA-CATENIN GENE; MURINE ALLANTOIS; VASCULAR
DEVELOPMENT; MOUSE EMBRYOS; DEFECTS; VASCULOGENESIS; MICE; HYALURONAN;
MESODERM
AB Loss of Tbx4 results in absence of chorio-allantoic fusion and failure of formation of the primary vascular plexus of the allantois leading to embryonic death at E10.5. We reviewed the literature for genes implicated in chorio-allantoic fusion, cavitation and vascular plexus formation, processes affected in Tbx4 mutant allantoises. Using this candidate gene approach, we identified a number of genes downstream of Tbx4 in the allantois including extracellular matrix molecules Vcan, Has2, and Itga5, transcription factors Snai1 and Twist, and signaling molecules Bmp2, Bmp7, Notch2, Jag1 and Wnt2. In addition, we show that the canonical Wnt signaling pathway contributes to the vessel-forming potential of the allantois. Ex vivo, the Tbx4 mutant phenotype can be rescued using agonists of the Wnt signaling pathway and, in wildtype allantoises, an inhibitor of the canonical Wnt signaling pathway disrupts vascular plexus formation. In vivo, Tbx4 and Wnt2 double heterozygous placentas show decreased vasculature suggesting interactions between Tbx4 and the canonical Wnt signaling pathway in the process of allantois-derived blood vessel formation.
C1 [Arora, Ripla; del Alcazar, Chelsea M.; Papaioannou, Virginia E.] Columbia Univ, Dept Genet & Dev, Med Ctr, New York, NY 10027 USA.
[Morrisey, Edward E.] Univ Penn, Dept Med & Cell & Dev Biol, Philadelphia, PA 19104 USA.
[Naiche, L. A.] NCI, Canc & Dev Biol Lab, Frederick, MD 21701 USA.
RP Arora, R (reprint author), Columbia Univ, Dept Genet & Dev, Med Ctr, New York, NY 10027 USA.
EM vep1@columbia.edu
OI Papaioannou, Virginia/0000-0001-7558-8601
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development (NICHD) [R37HD033082]
FX The project was supported by grant number R37HD033082 (V. E. P.) from
the Eunice Kennedy Shriver National Institute of Child Health and Human
Development (NICHD). The content is solely the responsibility of the
authors and does not necessarily represent the official views of the
NICHD or the 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 46
TC 5
Z9 5
U1 0
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 28
PY 2012
VL 7
IS 8
AR e43581
DI 10.1371/journal.pone.0043581
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 998CA
UT WOS:000308213600033
PM 22952711
ER
PT J
AU Reperant, LA
Kuiken, T
Grenfell, BT
Osterhaus, ADME
Dobson, AP
AF Reperant, Leslie A.
Kuiken, Thijs
Grenfell, Bryan T.
Osterhaus, Albert D. M. E.
Dobson, Andrew P.
TI Linking Influenza Virus Tissue Tropism to Population-Level Reproductive
Fitness
SO PLOS ONE
LA English
DT Article
ID ADAPTIVE IMMUNE-RESPONSE; LOWER RESPIRATORY-TRACT; A VIRUS; PANDEMIC
INFLUENZA; WITHIN-HOST; H5N1 VIRUS; RECEPTOR SPECIFICITY; METABOLIC
PROPERTIES; INFECTIOUS-DISEASES; HUMAN-LUNG
AB Influenza virus tissue tropism defines the host cells and tissues that support viral replication and contributes to determining which regions of the respiratory tract are infected in humans. The location of influenza virus infection along the respiratory tract is a key determinant of virus pathogenicity and transmissibility, which are at the basis of influenza burdens in the human population. As the pathogenicity and transmissibility of influenza virus ultimately determine its reproductive fitness at the population level, strong selective pressures will shape influenza virus tissue tropisms that maximize fitness. At present, the relationships between influenza virus tissue tropism within hosts and reproductive fitness at the population level are poorly understood. The selective pressures and constraints that shape tissue tropism and thereby influence the location of influenza virus infection along the respiratory tract are not well characterized. We use mathematical models that link within-host infection dynamics in a spatially-structured human respiratory tract to between-host transmission dynamics, with the aim of characterizing the possible selective pressures on influenza virus tissue tropism. The results indicate that spatial heterogeneities in virus clearance, virus pathogenicity or both, resulting from the unique structure of the respiratory tract, may drive optimal receptor binding affinity-that maximizes influenza virus reproductive fitness at the population level-towards sialic acids with alpha 2,6 linkage to galactose. The expanding cell pool deeper down the respiratory tract, in association with lower clearance rates, may result in optimal infectivity rates-that likewise maximize influenza virus reproductive fitness at the population level-to exhibit a decreasing trend towards deeper regions of the respiratory tract. Lastly, pre-existing immunity may drive influenza virus tissue tropism towards upper regions of the respiratory tract. The proposed framework provides a new template for the cross-scale study of influenza virus evolutionary and epidemiological dynamics in humans.
C1 [Reperant, Leslie A.; Kuiken, Thijs; Osterhaus, Albert D. M. E.] Erasmus MC, Dept Virol, Rotterdam, Netherlands.
[Reperant, Leslie A.; Grenfell, Bryan T.; Dobson, Andrew P.] Princeton Univ, Dept Ecol & Evolutionary Biol, Princeton, NJ 08544 USA.
[Grenfell, Bryan T.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
RP Reperant, LA (reprint author), Erasmus MC, Dept Virol, Rotterdam, Netherlands.
EM l.reperant@erasmusmc.nl
RI Barley, Kamal/F-9579-2011;
OI Barley, Kamal/0000-0003-1874-9813; Osterhaus,
Albert/0000-0002-6074-1172; Reperant, Leslie/0000-0002-7212-1595
FU Dutch Ministry of Economic Affairs; VIRGO Consortium; Dutch government
[BSIK03012]; European Commission [044490, 258084]; Science & Technology
Directorate, Department of Homeland Security; Fogarty International
Center, National Institutes of Health; NSF [0742373]; NIH [R01
GM083983-01]; ERC [250136]; EU [223498]
FX LAR, ADMEO and TK were supported by the Dutch Ministry of Economic
Affairs grant "Impuls Veterinair Influenza Onderzoek Nederland". ADMEO
and TK were supported by the VIRGO Consortium, an innovative cluster
approved by the Netherlands Genomics Initiative, and partially funded by
the Dutch government (grant number BSIK03012); European Commission grant
no. 044490 "New-FluBird", and European Commission grant no. 258084
"Flupig". BTG was supported by the RAPIDD program of the Science &
Technology Directorate, Department of Homeland Security, and the Fogarty
International Center, National Institutes of Health, and by grants NSF
0742373, and NIH R01 GM083983-01. ADMEO was supported by the ERC
advanced grant no. 250136 "FluPlan", and EU FP7 grant no. 223498
"Emperie". The funders had no role in study design, data collection and
analysis, decision to publish, or preparation of the manuscript.
NR 86
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U1 3
U2 21
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 28
PY 2012
VL 7
IS 8
AR e43115
DI 10.1371/journal.pone.0043115
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 998CA
UT WOS:000308213600016
PM 22952637
ER
PT J
AU Thurber, KR
Tycko, R
AF Thurber, Kent R.
Tycko, Robert
TI Theory for cross effect dynamic nuclear polarization under magic-angle
spinning in solid state nuclear magnetic resonance: The importance of
level crossings
SO JOURNAL OF CHEMICAL PHYSICS
LA English
DT Article
ID NMR-SPECTROSCOPY; 14.1 T; SPECTROMETER; RELAXATION; TRANSITION;
DIFFUSION; PROTEINS; SYSTEM
AB We present theoretical calculations of dynamic nuclear polarization (DNP) due to the cross effect in nuclear magnetic resonance under magic-angle spinning (MAS). Using a three-spin model (two electrons and one nucleus), cross effect DNP with MAS for electron spins with a large g-anisotropy can be seen as a series of spin transitions at avoided crossings of the energy levels, with varying degrees of adiabaticity. If the electron spin-lattice relaxation time T-1e is large relative to the MAS rotation period, the cross effect can happen as two separate events: (i) partial saturation of one electron spin by the applied microwaves as one electron spin resonance (ESR) frequency crosses the microwave frequency and (ii) flip of all three spins, when the difference of the two ESR frequencies crosses the nuclear frequency, which transfers polarization to the nuclear spin if the two electron spins have different polarizations. In addition, adiabatic level crossings at which the two ESR frequencies become equal serve to maintain non-uniform saturation across the ESR line. We present analytical results based on the Landau-Zener theory of adiabatic transitions, as well as numerical quantum mechanical calculations for the evolution of the time-dependent three-spin system. These calculations provide insight into the dependence of cross effect DNP on various experimental parameters, including MAS frequency, microwave field strength, spin relaxation rates, hyperfine and electron-electron dipole coupling strengths, and the nature of the biradical dopants. [http://dx.doi.org/10.1063/1.4747449]
C1 [Thurber, Kent R.; Tycko, Robert] NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
RP Thurber, KR (reprint author), NIDDKD, Chem Phys Lab, NIH, Bldg 2, Bethesda, MD 20892 USA.
EM thurberk@niddk.nih.gov
FU National Institute of Diabetes and Digestive and Kidney Diseases of the
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 of the
National Institutes of Health. We thank Dr. Kan-Nian Hu and Dr. Alexey
Potapov for helpful discussions about DNP mechanisms, and Dr. Akiva
Feintuch for discussions regarding the solid effect. Numerical
calculations used the high-performance computational capabilities of the
Biowulf Linux cluster at the National Institutes of Health.
NR 47
TC 63
Z9 63
U1 12
U2 90
PU AMER INST PHYSICS
PI MELVILLE
PA CIRCULATION & FULFILLMENT DIV, 2 HUNTINGTON QUADRANGLE, STE 1 N O 1,
MELVILLE, NY 11747-4501 USA
SN 0021-9606
J9 J CHEM PHYS
JI J. Chem. Phys.
PD AUG 28
PY 2012
VL 137
IS 8
AR 084508
DI 10.1063/1.4747449
PG 14
WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical
SC Chemistry; Physics
GA 000VB
UT WOS:000308416800042
PM 22938251
ER
PT J
AU Battisti, AJ
Meng, G
Winkler, DC
McGinnes, LW
Plevka, P
Steven, AC
Morrison, TG
Rossmann, MG
AF Battisti, Anthony J.
Meng, Geng
Winkler, Dennis C.
McGinnes, Lori W.
Plevka, Pavel
Steven, Alasdair C.
Morrison, Trudy G.
Rossmann, Michael G.
TI Structure and assembly of a paramyxovirus matrix protein
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
ID NEWCASTLE-DISEASE VIRUS; RESPIRATORY SYNCYTIAL VIRUS; CRYSTAL-STRUCTURE;
SENDAI-VIRUS; PARTICLES; REVEALS; NUCLEOCAPSIDS; GLYCOPROTEINS;
ECTODOMAIN; EVOLUTION
AB Many pleomorphic, lipid-enveloped viruses encode matrix proteins that direct their assembly and budding, but the mechanism of this process is unclear. We have combined X-ray crystallography and cryoelectron tomography to show that the matrix protein of Newcastle disease virus, a paramyxovirus and relative of measles virus, forms dimers that assemble into pseudotetrameric arrays that generate the membrane curvature necessary for virus budding. We show that the glycoproteins are anchored in the gaps between the matrix proteins and that the helical nucleocapsids are associated in register with the matrix arrays. About 90% of virions lack matrix arrays, suggesting that, in agreement with previous biological observations, the matrix protein needs to dissociate from the viral membrane during maturation, as is required for fusion and release of the nucleocapsid into the host's cytoplasm. Structure and sequence conservation imply that other paramyxovirus matrix proteins function similarly.
C1 [Battisti, Anthony J.; Meng, Geng; Plevka, Pavel; Rossmann, Michael G.] Purdue Univ, Dept Biol Sci, W Lafayette, IN 47907 USA.
[Winkler, Dennis C.; Steven, Alasdair C.] NIAMSD, Struct Biol Res Lab, NIH, Bethesda, MD 20892 USA.
[McGinnes, Lori W.; Morrison, Trudy G.] Univ Massachusetts, Sch Med, Program Immunol & Virol, Dept Microbiol & Physiol Syst, Worcester, MA 01655 USA.
RP Rossmann, MG (reprint author), Purdue Univ, Dept Biol Sci, W Lafayette, IN 47907 USA.
EM mr@purdue.edu
RI Plevka, Pavel/H-8661-2014
OI Plevka, Pavel/0000-0003-4215-3315
FU US Department of Energy, Office of Science, Office of Basic Energy
Sciences [DE-AC02-06CH11357]; National Institutes of Health [AI11219];
National Institute of Arthritis and Musculoskeletal and Skin Diseases;
National Institutes of Health/General Medicine [T32 GM008296-20]; Purdue
University Graduate School
FX We thank Anastasia Aksyuk and Giovanni Cardone for helpful comments and
suggestions regarding image processing; Ken Hibler and Zhiheng Yu for
assistance with the FEI Titan Krios Microscope; Paul Chipman, Siyang
Sun, and Ye Xiang for helpful comments and suggestions throughout the
course of this project; Xinzheng Zhang for assistance with electron
microscopy; and Sheryl Kelly for help in the preparation of this
manuscript. Use of the Advanced Photon Source was supported by the US
Department of Energy, Office of Science, Office of Basic Energy Sciences
under Contract DE-AC02-06CH11357. We thank National Institutes of Health
for both an individual research award (AI11219 to M.G.R.) and support
via the intramural research program of National Institute of Arthritis
and Musculoskeletal and Skin Diseases (to A.C.S.). Support for A.J.B.
was provided by a Biophysics Training Grant (T32 GM008296-20) from the
National Institutes of Health/General Medicine (C.V. Stauffacher,
principal investigator) and a Bilsland Dissertation Fellowship from
Purdue University Graduate School.
NR 33
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Z9 32
U1 0
U2 20
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 28
PY 2012
VL 109
IS 35
BP 13996
EP 14000
DI 10.1073/pnas.1210275109
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 002VP
UT WOS:000308565300031
PM 22891297
ER
PT J
AU Shaked, H
Hofseth, LJ
Chumanevich, A
Chumanevich, AA
Wang, J
Wang, YS
Taniguchi, K
Guma, M
Shenouda, S
Clevers, H
Harris, CC
Karin, M
AF Shaked, Helena
Hofseth, Lorne J.
Chumanevich, Alena
Chumanevich, Alexander A.
Wang, Jin
Wang, Yinsheng
Taniguchi, Koji
Guma, Monica
Shenouda, Steve
Clevers, Hans
Harris, Curtis C.
Karin, Michael
TI Chronic epithelial NF-kappa B activation accelerates APC loss and
intestinal tumor initiation through iNOS up-regulation
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
ID NITRIC-OXIDE; COLORECTAL-CANCER; DNA-DAMAGE; TRANSCRIPTION FACTOR;
ULCERATIVE-COLITIS; COLON-CANCER; MOUSE MODEL; RAG2-DEFICIENT MICE;
MAMMALIAN-CELLS; APC(MIN/+) MICE
AB The role of NF-kappa B activation in tumor initiation has not been thoroughly investigated. We generated Ikk beta(EE)(IEC) transgenic mice expressing constitutively active I kappa B kinase beta (IKK beta) in intestinal epithelial cells (IECs). Despite absence of destructive colonic inflammation, Ikk beta(EE)(IEC) mice developed intestinal tumors after a long latency. However, when crossed to mice with IEC-specific allelic deletion of the adenomatous polyposis coli (Apc) tumor suppressor locus, Ikk beta(EE)(IEC) mice exhibited more beta-catenin(+) early lesions and visible small intestinal and colonic tumors relative to Apc(+/Delta IEC) mice, and their survival was severely compromised. IEC of Ikk beta(EE)(IEC) mice expressed high amounts of inducible nitric oxide synthase (iNOS) and elevated DNA damage markers and contained more oxidative DNA lesions. Treatment of Ikk beta(EE)(IEC)/Apc(+/Delta IEC) mice with an iNOS inhibitor decreased DNA damage markers and reduced early beta-catenin(+) lesions and tumor load. The results suggest that persistent NF-kappa B activation in IEC may accelerate loss of heterozygocity by enhancing nitrosative DNA damage.
C1 [Shaked, Helena; Taniguchi, Koji; Guma, Monica; Karin, Michael] Univ Calif San Diego, Sch Med, Dept Pharmacol, La Jolla, CA 92093 USA.
[Shenouda, Steve] Univ Calif San Diego, Lab Mucosal Immun, Sch Med, La Jolla, CA 92093 USA.
[Shenouda, Steve] Univ Calif San Diego, William K Warren Med Res Ctr Celiac Dis, Sch Med, La Jolla, CA 92093 USA.
[Hofseth, Lorne J.; Chumanevich, Alena; Chumanevich, Alexander A.] Univ S Carolina, S Carolina Coll Pharm, Dept Pharmaceut & Biomed Sci, Columbia, SC 29208 USA.
[Wang, Jin; Wang, Yinsheng] Univ Calif Riverside, Dept Chem, Riverside, CA 92521 USA.
[Taniguchi, Koji] Keio Univ, Sch Med, Dept Microbiol & Immunol, Tokyo 1608582, Japan.
[Clevers, Hans] Hubrecht Inst Dev Biol & Stem Cell Res, NL-3584 CT Utrecht, Netherlands.
[Harris, Curtis C.] NCI, Human Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA.
RP Karin, M (reprint author), Univ Calif San Diego, Sch Med, Dept Pharmacol, La Jolla, CA 92093 USA.
EM karinoffice@ucsd.edu
RI Shaked, Helena/M-9682-2014
FU National Institutes of Health [AI043477, CA101864]; William K. Warren
Foundation [DK035108]; Strategic Young Researcher Overseas Visits
Program for Accelerating Brain Circulation
FX This work was supported by National Institutes of Health Grants AI043477
(to M.K.) and CA101864 (to Y.W.), William K. Warren Foundation Grant
DK035108 (to M.K.), and the Strategic Young Researcher Overseas Visits
Program for Accelerating Brain Circulation (K.T.).
NR 55
TC 51
Z9 54
U1 0
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 28
PY 2012
VL 109
IS 35
BP 14007
EP 14012
DI 10.1073/pnas.1211509109
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 002VP
UT WOS:000308565300033
PM 22893683
ER
PT J
AU Lin, PL
Dartois, V
Johnston, PJ
Janssen, C
Via, L
Goodwin, MB
Klein, E
Barry, CE
Flynn, JL
AF Lin, Philana Ling
Dartois, Veronique
Johnston, Paul J.
Janssen, Christopher
Via, Laura
Goodwin, Michael B.
Klein, Edwin
Barry, Clifton E., III
Flynn, JoAnne L.
TI Metronidazole prevents reactivation of latent Mycobacterium tuberculosis
infection in macaques
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
ID CYNOMOLGUS MACAQUES; GUINEA-PIGS; MODEL; GRANULOMA; RESEMBLES; THERAPY;
DISEASE
AB Targeting Mycobacterium tuberculosis bacilli in low-oxygen microenvironments, such as caseous granulomas, has been hypothesized to have the potential to shorten therapy for active tuberculosis (TB) and prevent reactivation of latent infection. We previously reported that upon low-dose M. tuberculosis infection, equal proportions of cynomolgus macaques develop active disease or latent infection and that latently infected animals reactivated upon neutralization of TNF. Using this model we now show that chemoprophylaxis of latently infected cynomolgus macaques with 6 mo of isoniazid (INH) effectively prevented anti-TNF antibody-induced reactivation. Similarly, 2-mo treatment of latent animals with a combination of INH and rifampicin (RIF) was highly effective at preventing reactivation disease in this model. Metronidazole (MTZ), which has activity only against anaerobic, nonreplicating bacteria, was as effective as either of these treatments in preventing reactivation of latent infection. Because hypoxic lesions also occur during active TB, we further showed that addition of MTZ to INH/RIF effectively treated animals with active TB within 2 mo. Healing lesions were associated with distinct changes in cellular pathology, with a shift toward increasingly fibrotic and calcified lesions. Our data in the nonhuman primate model of active and latent TB supports targeting bacteria in hypoxic environments for preventing reactivation of latent infection and possibly shortening the duration of therapy in active TB.
C1 [Johnston, Paul J.; Flynn, JoAnne L.] Univ Pittsburgh, Sch Med, Dept Microbiol & Mol Genet, Pittsburgh, PA 15261 USA.
[Lin, Philana Ling] Univ Pittsburgh, Sch Med, Div Infect Dis, Dept Pediat,Childrens Hosp Pittsburgh UPMC, Pittsburgh, PA 15224 USA.
[Dartois, Veronique] Novartis Inst Trop Dis, Dept Pharmacol, Singapore, Singapore.
[Janssen, Christopher; Klein, Edwin] Univ Pittsburgh, Div Lab Anim Res, Pittsburgh, PA 15261 USA.
[Via, Laura; Goodwin, Michael B.; Barry, Clifton E., III] NIAID, TB Res Sect, NIH, Bethesda, MD 20892 USA.
RP Flynn, JL (reprint author), Univ Pittsburgh, Sch Med, Dept Microbiol & Mol Genet, Pittsburgh, PA 15261 USA.
EM joanne@pitt.edu
RI Barry, III, Clifton/H-3839-2012;
OI Via, Laura/0000-0001-6074-9521
FU National Institute of Allergy and Infectious Diseases
[HHSN266200400091C]; Bill and Melinda Gates Foundation; Otis Foundation;
National Institute of Allergy and Infectious Diseases, National
Institutes of Health
FX We thank Mark Rodgers, Lekneitah Smith, Catherine Cochran, Kang Min Low,
and Carolyn Bigbee for technical assistance; Melanie O'Malley, Jennifer
Kerr, Daniel Fillmore, and Jaime Tomko for veterinary technician
expertise; Matthew Bigbee for assistance with figures; Charles Scanga;
and the Grand Challenge 11 consortium members, particularly Douglas
Young, for invaluable advice and discussion on research design and
interpretation and for comments on the manuscript. BEI Resources,
National Institute of Allergy and Infectious Diseases Contract
HHSN266200400091C, provided Culture Filtrate Protein. This study was
funded by the Bill and Melinda Gates Foundation Grand Challenge 11
"Drugs for Latent TB"; the Otis Foundation (P.L.L.); and, in part, by
the Intramural Research Program of the National Institute of Allergy and
Infectious Diseases, National Institutes of Health.
NR 26
TC 45
Z9 45
U1 0
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 28
PY 2012
VL 109
IS 35
BP 14188
EP 14193
DI 10.1073/pnas.1121497109
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 002VP
UT WOS:000308565300064
PM 22826237
ER
PT J
AU Singh, A
Hodgson, N
Yan, M
Joo, J
Gu, L
Sang, H
Gregory-Bryson, E
Wood, WG
Ni, YS
Smith, K
Jackson, SH
Coleman, WG
AF Singh, Aparna
Hodgson, Nathaniel
Yan, Ming
Joo, Jungsoo
Gu, Lei
Sang, Hong
Gregory-Bryson, Emmalena
Wood, William G.
Ni, Yisheng
Smith, Kimberly
Jackson, Sharon H.
Coleman, William G.
TI Screening Helicobacter pylori genes induced during infection of mouse
stomachs
SO WORLD JOURNAL OF GASTROENTEROLOGY
LA English
DT Article
DE Helicobacter pylori; In vivo expression technology; Virulence genes;
Mice; Infection
ID VIVO EXPRESSION TECHNOLOGY; DNA ADENINE METHYLATION; BACTERIAL GENES;
ESCHERICHIA-COLI; VIRULENCE GENES; HOST TISSUES; CAGA PROTEIN;
SELECTION; REPLICATION; SHIGELLA
AB AIM: To investigate the effect of in vivo environment on gene expression in Helkobacter pylori (H. pylon) as it relates to its survival in the host.
METHODS: In vivo expression technology (IVET) systems are used to identify microbial virulence genes. We modified the DIET-transcriptional fusion vector, pIVET8, which uses antibiotic resistance as the basis for selection of candidate genes in host tissues to develop two unique IVET-promoter-screening vectors, pIVET11 and pIVET12. Our novel IVET systems were developed by the fusion of random Sau3A DNA fragments of H. pylori and a tandem-reporter system of chloramphenicol acetyltransferase and beta-galactosidase. Additionally, each vector contains a kanamycin resistance gene. We used a mouse macrophage cell line, RAW 264.7 and mice, as selective media to identify specific genes that H. pylori expresses in vivo. Gene expression studies were conducted by infecting RAW 264.7 cells with H. pylori. This was followed by real time polymerase chain reaction (PCR) analysis to determine the relative expression levels of in vivo induced genes.
RESULTS: In this study, we have identified 31 in vivo induced (ivi) genes in the initial screens. These 31 genes belong to several functional gene families, including several well-known virulence factors that are expressed by the bacterium in infected mouse stomachs. Virulence factors, vacA and cagA, were found in this screen and are known to play important roles in H. pylori infection, colonization and pathogenesis. Their detection validates the efficacy of these screening systems. Some of the identified ivi genes have already been implicated to play an important role in the pathogenesis of H. pylon and other bacterial pathogens such as Escherichia coli and Vibrio cholerae. Transcription profiles of all ivi genes were confirmed by real time PCR analysis of H. pylori RNA isolated from H. pylori infected RAW 264.7 macrophages. We compared the expression profile of H. pylori and RAW 264.7 coculture with that of H. pylori only. Some genes such as cagA, vacA, IpxC, murI, tlpC, trxB, sodB, tnpB, pgi, rbfA and infB showed a 2-20 fold upregulation. Statistically significant upregulation was obtained for all the above mentioned genes (P < 0.05). tlpC, cagA, vacA, sodB, rbfA, tnpB, IpxC and murl were also significantly upregulated (P < 0.01). These data suggest a strong correlation between results obtained in vitro in the macrophage cell line and in the intact animal.
CONCLUSION: The positive identification of these genes demonstrates that our IVET systems are powerful tools for studying H. pylori gene expression in the host environment. (C) 2012 Baishideng. All rights reserved.
C1 [Singh, Aparna; Hodgson, Nathaniel; Yan, Ming; Joo, Jungsoo; Gu, Lei; Sang, Hong; Gregory-Bryson, Emmalena; Ni, Yisheng; Smith, Kimberly; Coleman, William G.] NIDDK, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA.
[Wood, William G.; Jackson, Sharon H.] NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA.
RP Coleman, WG (reprint author), NIDDK, Lab Biochem & Genet, NIH, Bldg 8,Room 2A02,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM wc3z@nih.gov
FU National Institutes of Health, National Institute of Diabetes and
Digestive and Kidney Disease; Division of Intramural Research of the
National Institute of Allergy and Infectious Diseases; National
Institute on Minority Health and Health Disparities [Y3-DK-3521-07]
FX Supported by Intramural Research Program of the National Institutes of
Health, National Institute of Diabetes and Digestive and Kidney Disease;
The Division of Intramural Research of the National Institute of Allergy
and Infectious Diseases; An Inter-Agency Agreement (Y3-DK-3521-07) with
the National Institute on Minority Health and Health Disparities
NR 52
TC 7
Z9 7
U1 0
U2 12
PU BAISHIDENG PUBLISHING GROUP INC
PI PLEASANTON
PA 8226 REGENCY DR, PLEASANTON, CA 94588 USA
SN 1007-9327
EI 2219-2840
J9 WORLD J GASTROENTERO
JI World J. Gastroenterol.
PD AUG 28
PY 2012
VL 18
IS 32
BP 4323
EP 4334
DI 10.3748/wjg.v18.i32.4323
PG 12
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 005VZ
UT WOS:000308779500009
PM 22969195
ER
PT J
AU Chirenje, ZM
Masse, BR
Maslankowski, LA
Ramjee, G
Coletti, AS
Tembo, TN
Magure, TM
Soto-Torres, L
Kelly, C
Hillier, S
Karim, A
AF Chirenje, Zvavahera M.
Masse, Benoit R.
Maslankowski, Lisa A.
Ramjee, Gita
Coletti, Anne S.
Tembo, Tchangani N.
Magure, Tsitsi M.
Soto-Torres, Lydia
Kelly, Cliff
Hillier, Sharon
Karim, Abdool
TI Utility of colposcopy in a phase 2 portion of a microbicide clinical
trial of BufferGel and 0.5% PRO 2000 Gel
SO JOURNAL OF THE INTERNATIONAL AIDS SOCIETY
LA English
DT Article
DE colposcopic evaluations; topical microbicides; genital epithelium; phase
2; HIV; investigational product
ID HIV-1 INFECTION; VAGINAL GEL; PREVENTION; TRANSMISSION; SAFETY; WOMEN;
NONOXYNOL-9; HEALTHY
AB Background: The majority of new HIV infections are acquired through heterosexual transmission. There is urgent need for prevention methods to compliment behavior change and condom use. Topical microbicide represent a potential strategy for reduction of HIV transmission in women.
Methods: Monthly Colposcopy evaluations were performed during pelvic examinations among 299 women enrolled in the Phase 2 portion of HPTN 035 study at four sites (1 in USA, 3 in Southern Africa). This was a phase 2/2b, multisite, randomized, and controlled clinical trial with four arms: BufferGel, 0.5% PRO2000 Gel, placebo gel and no gel. At two of the sites, pelvic examinations were conducted by the use of naked eye without colposcopy.
Results: A colposcopy finding of any kind was detected in 48% of participants at baseline compared to 40% at 3 months (p = 0.04). The lower rates were also observed in vaginal discharge (22% at baseline, 16% at 3 months, p = 0.06), erythema (15% at baseline, 8% at 3 months, p = 0.004). The trend towards significance at p = 0.05 disappear when utilizing stringent statistical significance levels. A pelvic finding of any kind was detected in 71% of colposcopy participants compared to 41% of participants who had naked eye examination only conducted at two sites that performed both colposcopy and naked eye without colposcopy. Use of colposcopy yielded significantly higher rates of participants with deep epithelial disruption, erythema and ecchymosis. We observed no cases of incident Chlamydia, Gonorrhea, or Syphilis during the three month follow up. There were 2 cases of incident HIV during 3-month study period neither of which was associated with any abnormal colposcopy evaluation findings.
Conclusion: No safety signals were observed in the 4 study arms, allowing seamless transition from phase 2 to 2b. Colposcopy utility in microbicide clinical trials has minimal value given high rates of background noise findings of no relevant clinical significance.
C1 [Masse, Benoit R.; Kelly, Cliff] Fred Hutchinson Canc Res Ctr, SCHARP, Seattle, WA 98104 USA.
[Maslankowski, Lisa A.] Univ Penn, Dept Obstet & Gynecol, Philadelphia, PA 19104 USA.
[Ramjee, Gita] Med Res Council S Africa, Durban, South Africa.
[Coletti, Anne S.] Fhi360, Durham, NC USA.
[Tembo, Tchangani N.] Univ N Carolina Project, Lilongwe, Malawi.
[Soto-Torres, Lydia] NIAID, Bethesda, MD 20892 USA.
[Hillier, Sharon] Magee Womens Res Inst, Dept Obstet Gynecol & Reprod Sci, Pittsburgh, PA USA.
[Karim, Abdool] Doris Duke Med Res Inst, Ctr AIDS Program Res S Africa, Congella, South Africa.
[Chirenje, Zvavahera M.; Magure, Tsitsi M.] Univ Zimbabwe, Coll Hlth Sci, Dept Obstet & Gynaecol, Harare, Zimbabwe.
RP Chirenje, ZM (reprint author), Univ Zimbabwe, Coll Hlth Sci, Dept Obstet & Gynaecol, POB A178, Harare, Zimbabwe.
EM chirenje@uz-ucsf.co.zw
OI Masse, Benoit/0000-0002-4944-8098
FU US National Institutes of Health (NIH); National Institute of Allergy
and infectious Diseases (NIAID); National Institute of Child Health and
Development (NICHD); National Institute of Drug Abuse (NIDA); National
Institute of Mental Health (NIMH); NIAID of the U.S. National Institutes
of Health [5UM1AI068633]; NICHD of the U.S. National Institutes of
Health [5UM1AI068633]; NIMH U.S. National Institutes of Health
[5UM1AI068633]
FX We would like to thank all the women who participated in this study. The
study was sponsored by the US National Institutes of Health (NIH). The
study was designed and implemented by HIV Prevention trials Network
(HPTN) and the Microbicide Trials Network (MTN). The HPTN (UM1AI46749)
has been funded by the National Institute of Allergy and infectious
Diseases (NIAID), National Institute of Child Health and Development
(NICHD), National Institute of Drug Abuse (NIDA), and National Institute
of Mental Health (NIMH). MTN is funded by NIAID, NICHD and NIMH, all of
the U.S. National Institutes of Health (5UM1AI068633).
NR 21
TC 1
Z9 1
U1 1
U2 1
PU INT AIDS SOCIETY
PI GENEVA
PA AVENUE DE FRANCE 23, GENEVA, 1202, SWITZERLAND
SN 1758-2652
J9 J INT AIDS SOC
JI J. Int. AIDS Soc.
PD AUG 27
PY 2012
VL 15
AR 17376
DI 10.7448/IAS.15.2.17376
PG 8
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 025PM
UT WOS:000310203900001
PM 22944480
ER
PT J
AU Meredith, MM
Liu, K
Kamphorst, AO
Idoyaga, J
Yamane, A
Guermonprez, P
Rihn, S
Yao, KH
Silva, IT
Oliveira, TY
Skokos, D
Casellas, R
Nussenzweig, MC
AF Meredith, Matthew M.
Liu, Kang
Kamphorst, Alice O.
Idoyaga, Juliana
Yamane, Arito
Guermonprez, Pierre
Rihn, Suzannah
Yao, Kai-Hui
Silva, Israel T.
Oliveira, Thiago Y.
Skokos, Dimitris
Casellas, Rafael
Nussenzweig, Michel C.
TI Zinc finger transcription factor zDC is a negative regulator required to
prevent activation of classical dendritic cells in the steady state
SO JOURNAL OF EXPERIMENTAL MEDICINE
LA English
DT Article
ID GERMINAL-CENTER FORMATION; IN-VIVO; LYMPH-NODE; COMMITTED PROGENITORS;
LINEAGE COMMITMENT; IMMUNE-SYSTEM; EXPRESSION; INFLAMMATION; BCL-6;
HOMEOSTASIS
AB Classical dendritic cells (cDCs) process and present antigens to T cells. Under steady-state conditions, antigen presentation by cDCs induces tolerance. In contrast, during infection or inflammation, cDCs become activated, express higher levels of cell surface MHC molecules, and induce strong adaptive immune responses. We recently identified a cDC-restricted zinc finger transcription factor, zDC (also known as Zbtb46 or Btbd4), that is not expressed by other immune cell populations, including plasmacytoid DCs, monocytes, or macrophages. We define the zDC consensus DNA binding motif and the genes regulated by zDC using chromatin immunoprecipitation and deep sequencing. By deleting zDC from the mouse genome, we show that zDC is primarily a negative regulator of cDC gene expression. zDC deficiency alters the cDC subset composition in the spleen in favor of CD8(+) DCs, up-regulates activation pathways in steady-state cDCs, including elevated MHC II expression, and enhances cDC production of vascular endothelial growth factor leading to increased vascularization of skin-draining lymph nodes. Consistent with these observations, zDC protein expression is rapidly down-regulated after TLR stimulation. Thus, zDC is a TLR-responsive, cDC-specific transcriptional repressor that is in part responsible for preventing cDC maturation in the steady state.
C1 [Meredith, Matthew M.; Kamphorst, Alice O.; Guermonprez, Pierre; Yao, Kai-Hui; Silva, Israel T.; Oliveira, Thiago Y.; Nussenzweig, Michel C.] Rockefeller Univ, Lab Mol Immunol, New York, NY 10065 USA.
[Idoyaga, Juliana] Rockefeller Univ, Cellular Physiol & Immunol Lab, New York, NY 10065 USA.
[Rihn, Suzannah] Rockefeller Univ, Aaron Diamond AIDS Res Ctr, New York, NY 10065 USA.
[Liu, Kang] Columbia Univ, Dept Microbiol & Immunol, New York, NY 10032 USA.
[Kamphorst, Alice O.] Emory Univ, Sch Med, Emory Vaccine Ctr, Atlanta, GA 30322 USA.
[Yamane, Arito; Casellas, Rafael] NIAMSD, NIH, Bethesda, MD 20892 USA.
[Skokos, Dimitris] Regeneron Pharmaceut Inc, Tarrytown, NY 10591 USA.
[Nussenzweig, Michel C.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA.
RP Nussenzweig, MC (reprint author), Rockefeller Univ, Lab Mol Immunol, New York, NY 10065 USA.
EM nussen@rockefeller.edu
RI Yamane, Arito/A-2959-2013; Silva, Israel/N-3858-2014;
OI Silva, Israel/0000-0002-4687-1499; Oliveira, Thiago/0000-0002-2654-0879
FU NIH [AI051573]; NIH Immunity and Infectious Disease Training Grant; Dana
Neuroimmunology grant; Columbia University Medical Center Skin Disease
Research Center (CUMCSDRC) [P30 AR044535/AR/NIAMS/NIH]
FX This work was supported in part by NIH grant number AI051573. M.M.
Meredith was supported by an NIH Immunity and Infectious Disease
Training Grant. K. Liu was supported by Dana Neuroimmunology grant and a
Pilot Grant funded by P30 AR044535/AR/NIAMS/NIH Columbia University
Medical Center Skin Disease Research Center (CUMCSDRC). M.C. Nussenzweig
is an HHMI investigator.
NR 47
TC 47
Z9 47
U1 0
U2 7
PU ROCKEFELLER UNIV PRESS
PI NEW YORK
PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA
SN 0022-1007
J9 J EXP MED
JI J. Exp. Med.
PD AUG 27
PY 2012
VL 209
IS 9
BP 1583
EP 1593
DI 10.1084/jem.20121003
PG 11
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA 000XK
UT WOS:000308423900006
PM 22851594
ER
PT J
AU Cataisson, C
Salcedo, R
Hakim, S
Moffitt, BA
Wright, L
Yi, M
Stephens, R
Dai, RM
Lyakh, L
Schenten, D
Yuspa, HS
Trinchieri, G
AF Cataisson, Christophe
Salcedo, Rosalba
Hakim, Shakeeb
Moffitt, B. Andrea
Wright, Lisa
Yi, Ming
Stephens, Robert
Dai, Ren-Ming
Lyakh, Lyudmila
Schenten, Dominik
Yuspa, H. Stuart
Trinchieri, Giorgio
TI IL-1R-MyD88 signaling in keratinocyte transformation and carcinogenesis
SO JOURNAL OF EXPERIMENTAL MEDICINE
LA English
DT Article
ID PROTEIN-KINASE-C; NF-KAPPA-B; SQUAMOUS-CELL CARCINOMA;
DIFFERENTIATION-ASSOCIATED KERATINS; PROMOTES TUMOR-GROWTH; SKIN
CARCINOGENESIS; ONCOGENIC RAS; IN-VIVO; INTRAEPIDERMAL INFLAMMATION;
TARGETED DISRUPTION
AB Constitutively active RAS plays a central role in the development of human cancer and is sufficient to induce tumors in two-stage skin carcinogenesis. RAS-mediated tumor formation is commonly associated with up-regulation of cytokines and chemokines that mediate an inflammatory response considered relevant to oncogenesis. In this study, we report that mice lacking IL-1R or MyD88 are less sensitive to topical skin carcinogenesis than their respective wild-type (WT) controls. MyD88(-/-) or IL-1R(-/-) keratinocytes expressing oncogenic RAS are hyperproliferative and fail to up-regulate proinflammatory genes or down-regulate differentiation markers characteristic of RAS-expressing WT keratinocytes. Although RAS-expressing MyD88(-/-) keratinocytes form only a few small tumors in orthotopic grafts, IL-1R-deficient RAS-expressing keratinocytes retain the ability to form tumors in orthotopic grafts. Using both genetic and pharmacological approaches, we find that the differentiation and proinflammatory effects of oncogenic RAS in keratinocytes require the establishment of an autocrine loop through IL-1 alpha, IL-1R, and MyD88 leading to phosphorylation of I kappa B alpha and NF-kappa B activation. Blocking IL-1 alpha-mediated NF-kappa B activation in RAS-expressing WT keratinocytes reverses the differentiation defect and inhibits proinflammatory gene expression. Collectively, these results demonstrate that MyD88 exerts a cell-intrinsic function in RAS-mediated transformation of keratinocytes.
C1 [Cataisson, Christophe; Hakim, Shakeeb; Moffitt, B. Andrea; Wright, Lisa; Yuspa, H. Stuart] NCI, Lab Canc Biol & Genet, Bethesda, MD 20892 USA.
[Dai, Ren-Ming; Lyakh, Lyudmila; Trinchieri, Giorgio] NCI, Canc & Inflammat Program, Bethesda, MD 20892 USA.
[Yi, Ming; Stephens, Robert] Adv Biomed Comp Ctr, Informat Syst Program, Frederick, MD 21701 USA.
[Salcedo, Rosalba; Dai, Ren-Ming] SAIC Frederick Inc, Frederick, MD 21701 USA.
[Schenten, Dominik] Yale Univ, Sch Med, Dept Immunobiol, New Haven, CT 06510 USA.
[Schenten, Dominik] Yale Univ, Sch Med, Howard Hughes Med Inst, New Haven, CT 06510 USA.
RP Yuspa, HS (reprint author), NCI, Lab Canc Biol & Genet, Bethesda, MD 20892 USA.
EM yuspas@mail.nih.gov; trinchig@mail.nih.gov
OI Moffitt, Andrea/0000-0001-5964-7851
FU Intramural Research Program, Center for Cancer Research, National Cancer
Institute, National Institutes of Health
FX This work was supported by the Intramural Research Program, Center for
Cancer Research, National Cancer Institute, National Institutes of
Health.
NR 79
TC 40
Z9 42
U1 0
U2 6
PU ROCKEFELLER UNIV PRESS
PI NEW YORK
PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA
SN 0022-1007
J9 J EXP MED
JI J. Exp. Med.
PD AUG 27
PY 2012
VL 209
IS 9
BP 1689
EP 1702
DI 10.1084/jem.20101355
PG 14
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA 000XK
UT WOS:000308423900013
PM 22908325
ER
PT J
AU Wray, S
Self, M
Lewis, PA
Taanman, JW
Ryan, NS
Mahoney, CJ
Liang, YY
Devine, MJ
Sheerin, UM
Houlden, H
Morris, HR
Healy, D
Marti-Masso, JF
Preza, E
Barker, S
Sutherland, M
Corriveau, RA
D'Andrea, M
Schapira, AHV
Uitti, RJ
Guttman, M
Opala, G
Jasinska-Myga, B
Puschmann, A
Nilsson, C
Espay, AJ
Slawek, J
Gutmann, L
Boeve, BF
Boylan, K
Stoessl, AJ
Ross, OA
Maragakis, NJ
Van Gerpen, J
Gerstenhaber, M
Gwinn, K
Dawson, TM
Isacson, O
Marder, KS
Clark, LN
Przedborski, SE
Finkbeiner, S
Rothstein, JD
Wszolek, ZK
Rossor, MN
Hardy, J
AF Wray, Selina
Self, Matthew
Lewis, Patrick A.
Taanman, Jan-Willem
Ryan, Natalie S.
Mahoney, Colin J.
Liang, Yuying
Devine, Michael J.
Sheerin, Una-Marie
Houlden, Henry
Morris, Huw R.
Healy, Daniel
Marti-Masso, Jose-Felix
Preza, Elisavet
Barker, Suzanne
Sutherland, Margaret
Corriveau, Roderick A.
D'Andrea, Michael
Schapira, Anthony H. V.
Uitti, Ryan J.
Guttman, Mark
Opala, Grzegorz
Jasinska-Myga, Barbara
Puschmann, Andreas
Nilsson, Christer
Espay, Alberto J.
Slawek, Jaroslaw
Gutmann, Ludwig
Boeve, Bradley F.
Boylan, Kevin
Stoessl, A. Jon
Ross, Owen A.
Maragakis, Nicholas J.
Van Gerpen, Jay
Gerstenhaber, Melissa
Gwinn, Katrina
Dawson, Ted M.
Isacson, Ole
Marder, Karen S.
Clark, Lorraine N.
Przedborski, Serge E.
Finkbeiner, Steven
Rothstein, Jeffrey D.
Wszolek, Zbigniew K.
Rossor, Martin N.
Hardy, John
CA NINDS Parkinson's Dis IPSC
NINDS Huntington's Dis IPSC
NINDS ALS IPSC Consortium
TI Creation of an Open-Access, Mutation-Defined Fibroblast Resource for
Neurological Disease Research
SO PLOS ONE
LA English
DT Article
ID FAMILIAL ALZHEIMERS-DISEASE; PLURIPOTENT STEM-CELLS;
ONSET-PARKINSON-DISEASE; AUTOSOMAL-DOMINANT PARKINSONISM;
AMYOTROPHIC-LATERAL-SCLEROSIS; FRONTOTEMPORAL LOBAR DEGENERATION;
ALPHA-SYNUCLEIN LOCUS; HUMAN SOMATIC-CELLS; CLINICAL-FEATURES; MISSENSE
MUTATIONS
AB Our understanding of the molecular mechanisms of many neurological disorders has been greatly enhanced by the discovery of mutations in genes linked to familial forms of these diseases. These have facilitated the generation of cell and animal models that can be used to understand the underlying molecular pathology. Recently, there has been a surge of interest in the use of patient-derived cells, due to the development of induced pluripotent stem cells and their subsequent differentiation into neurons and glia. Access to patient cell lines carrying the relevant mutations is a limiting factor for many centres wishing to pursue this research. We have therefore generated an open-access collection of fibroblast lines from patients carrying mutations linked to neurological disease. These cell lines have been deposited in the National Institute for Neurological Disorders and Stroke (NINDS) Repository at the Coriell Institute for Medical Research and can be requested by any research group for use in in vitro disease modelling. There are currently 71 mutation-defined cell lines available for request from a wide range of neurological disorders and this collection will be continually expanded. This represents a significant resource that will advance the use of patient cells as disease models by the scientific community.
C1 [Wray, Selina; Lewis, Patrick A.; Devine, Michael J.; Sheerin, Una-Marie; Houlden, Henry; Preza, Elisavet; Hardy, John] UCL, Dept Mol Neurosci, Inst Neurol, London, England.
[Self, Matthew; D'Andrea, Michael] Coriell Inst Med Res, Camden, NJ USA.
[Ryan, Natalie S.; Mahoney, Colin J.; Liang, Yuying; Barker, Suzanne; Rossor, Martin N.] UCL, Dementia Res Ctr, Dept Neurodegenerat Dis, Inst Neurol, London, England.
[Taanman, Jan-Willem; Healy, Daniel; Schapira, Anthony H. V.] UCL, Dept Clin Neurosci, Inst Neurol, London, England.
[Morris, Huw R.] Univ Cardiff, Sch Med, Cardiff, S Glam, Wales.
[Marti-Masso, Jose-Felix] Hosp Donastia, San Sebastian, Spain.
[Sutherland, Margaret; Corriveau, Roderick A.] NINDS, NIH, Bethesda, MD 20892 USA.
[Uitti, Ryan J.; Boylan, Kevin; Ross, Owen A.; Van Gerpen, Jay; Wszolek, Zbigniew K.] Mayo Clin, Dept Neurol, Jacksonville, FL 32224 USA.
[Uitti, Ryan J.; Boylan, Kevin; Ross, Owen A.; Van Gerpen, Jay; Wszolek, Zbigniew K.] Mayo Clin, Dept Neurosci, Jacksonville, FL 32224 USA.
[Guttman, Mark] Ctr Movement Disorders, Dept Neurol, Toronto, ON, Canada.
[Opala, Grzegorz; Jasinska-Myga, Barbara] Med Univ Silesia, Dept Neurol, Katowice, Poland.
[Puschmann, Andreas; Nilsson, Christer] Lund Univ, Dept Geriatr Psychiat, Lund, Sweden.
[Espay, Alberto J.] Univ Cincinnati, Dept Neurol, Cincinnati, OH USA.
[Slawek, Jaroslaw] Med Univ Gdansk, Dept Neurol & Psychiat Nursing, Gdansk, Poland.
[Gutmann, Ludwig] W Virginia Univ, Dept Neurol, Morgantown, WV 26506 USA.
[Boeve, Bradley F.] Mayo Clin, Dept Neurol, Rochester, MN USA.
[Stoessl, A. Jon] Univ British Columbia, Div Neurol, Pacific Parkinsons Res Ctr, Vancouver, BC V5Z 1M9, Canada.
[Maragakis, Nicholas J.] Johns Hopkins Univ, Dept Neurol & Neurosci, Sch Med, Baltimore, MD USA.
[Gerstenhaber, Melissa; Rothstein, Jeffrey D.] Johns Hopkins Univ, Dept Psychiat & Behav Sci, Sch Med, Baltimore, MD USA.
[Dawson, Ted M.] Johns Hopkins Univ, Neuroregenerat Program, Inst Cell Engn, Dept Neurol, Baltimore, MD USA.
[Dawson, Ted M.] Johns Hopkins Univ, Solomon H Snyder Dept Neurosci, Baltimore, MD USA.
[Isacson, Ole] Harvard Univ, Sch Med, Ctr Neuroregenerat Res, Belmont, MA 02178 USA.
[Marder, Karen S.; Clark, Lorraine N.] Columbia Univ, Gertrude H Sergievsky Ctr, Dept Neurol, New York, NY 10027 USA.
[Marder, Karen S.; Clark, Lorraine N.] Columbia Univ, Taub Inst, Coll Phys & Surg, New York, NY USA.
[Przedborski, Serge E.] Columbia Univ, Ctr Motor Neuron Biol & Dis, Dept Neurol, Coll Phys & Surg, New York, NY USA.
[Przedborski, Serge E.] Columbia Univ, Ctr Motor Neuron Biol & Dis, Dept Pathol, Coll Phys & Surg, New York, NY USA.
[Przedborski, Serge E.] Columbia Univ, Ctr Motor Neuron Biol & Dis, Dept Cell Biol, Coll Phys & Surg, New York, NY USA.
[Gwinn, Katrina] Baylor Coll Med, Dept Genet, Houston, TX 77030 USA.
[Finkbeiner, Steven] Univ Calif San Francisco, Dept Neurol, Gladstone Inst Neurol Dis, Taube Koret Ctr Huntingtons Dis Res, San Francisco, CA USA.
[Finkbeiner, Steven] Univ Calif San Francisco, Dept Physiol, Gladstone Inst Neurol Dis, Taube Koret Ctr Huntingtons Dis Res, San Francisco, CA USA.
RP Wray, S (reprint author), UCL, Dept Mol Neurosci, Inst Neurol, London, England.
EM j.hardy@ucl.ac.uk
RI Morris, Huw/B-8527-2008; Wray, Selina/C-3682-2009; Hardy,
John/C-2451-2009; Taanman, Jan/A-5379-2011; Kemp, Paul/A-4634-2010;
Lewis , Patrick/C-3674-2009; Preza, Elisavet/C-1829-2013; rothstein,
jeffrey/C-9470-2013; Ross, Owen/D-7573-2013; Schapira,
Anthony/A-1245-2010; Houlden, Henry/C-1532-2008; Marti Masso, Jose
Felix/D-8619-2013
OI CATTANEO, ELENA/0000-0002-0755-4917; Espay, Alberto/0000-0002-3389-136X;
Puschmann, Andreas/0000-0002-3201-8198; Lewis,
Patrick/0000-0003-4537-0489; Devine, Mike/0000-0001-6076-3382; Gwinn,
Katrina/0000-0002-8277-651X; Morris, Huw/0000-0002-5473-3774; Wray,
Selina/0000-0003-3062-7050; Taanman, Jan/0000-0002-5476-9785; Kemp,
Paul/0000-0003-2773-973X; Schapira, Anthony/0000-0002-3018-3966;
Houlden, Henry/0000-0002-2866-7777; Marti Masso, Jose
Felix/0000-0001-8428-4386
FU Alzheimer's Research UK; Alzheimer's Society; Parkinson's UK; Medical
Research Council; National Institute of Neurological Disorders and
Stroke (National Institute of Neurological Disorders and Stroke/National
Institutes of Health) [NS38377, NS060113, NS036630, NS050487]; GO grants
[RC2NS069395, RC2NS069422, RC2 NS070276]; Mayo Clinic Morris K. Udall
Center [P50NS072187, P50 NS072187-01S2]; Columbia Udall grant
[P50NS38370]; MDSCF grant [2007-MSCRFI-0420-00]; Parkinson's Disease
Foundation; Swedish Parkinson Academy; Michael J. Fox Foundation;
Department of Health's National Institute for Health Research Biomedical
Research Centres funding scheme; Wellcome Trust/Medical Research Council
(MRC) [WT089698]; P2ALS
FX This work was supported by the following grants and funding agencies:
Alzheimer's Research UK (SW and JH), The Alzheimer's Society (MNR),
Parkinson's UK (PAL and JH), the Medical Research Council, the National
Institute of Neurological Disorders and Stroke (National Institute of
Neurological Disorders and Stroke/National Institutes of Health grants
NS38377 [TD], NS060113 [LNC], NS036630 [KSM], NS050487 [LNC]), GO grants
RC2NS069395, RC2NS069422, RC2 NS070276, Mayo Clinic Morris K. Udall
Center grants P50NS072187 and P50 NS072187-01S2 (ZKW, RJU, OAR),
Columbia Udall grant P50NS38370 (SP), MDSCF grant 2007-MSCRFI-0420-00
(TD), P2ALS (JDR), The Parkinson's Disease Foundation (LNC, SP, KSM),
The Swedish Parkinson Academy (AP and CN) and the Michael J. Fox
Foundation (JH, KSM, LNC). This work was partly undertaken at University
College London Hospitals/University College London (UCL), which receives
a proportion of funding from the Department of Health's National
Institute for Health Research Biomedical Research Centres funding
scheme. This work was also supported in part by the Wellcome
Trust/Medical Research Council (MRC) Joint Call in Neurodegeneration
award (WT089698) to the UK Parkinson's Disease Consortium, whose members
are from the UCL Institute of Neurology, the University of Sheffield,
and the MRC Protein Phosphorylation Unit at the University of Dundee.
The funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 64
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U1 0
U2 20
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 27
PY 2012
VL 7
IS 8
AR e43099
DI 10.1371/journal.pone.0043099
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 995WH
UT WOS:000308044800019
PM 22952635
ER
PT J
AU Laurence, A
Amarnath, S
Mariotti, J
Kim, YC
Foley, J
Eckhaus, M
O'Shea, JJ
Fowler, DH
AF Laurence, Arian
Amarnath, Shoba
Mariotti, Jacopo
Kim, Yong Chan
Foley, Jason
Eckhaus, Michael
O'Shea, John J.
Fowler, Daniel H.
TI STAT3 Transcription Factor Promotes Instability of nTreg Cells and
Limits Generation of iTreg Cells during Acute Murine Graft-versus-Host
Disease
SO IMMUNITY
LA English
DT Article
ID REGULATORY T-CELLS; BONE-MARROW-TRANSPLANTATION; TGF-BETA; IN-VIVO;
FOXP3 EXPRESSION; TH17 CELLS; HELPER-CELLS; DIFFERENTIATION; PROGRAM;
T(H)17
AB Acute graft-versus-host disease (GvHD) is a major cause of mortality in allogeneic bone marrow transplantation (BMT), for which administration of FoxP3(+) regulatory T (Treg) cells has been proposed as a therapy. However, the phenotypic stability of Treg cells is controversial, and STAT3-dependent cytokines can inhibit FoxP3 expression. We assessed whether the elimination of STAT3 in T cells could limit the severity of GvHD. We found STAT3 limited FoxP3(+) Treg cell numbers following allogeneic BMT by two pathways: instability of natural Treg (nTreg) cells and inhibition of induced Treg (iTreg) cell polarization from naive CD4(+) T cells. Deletion of STAT3 within only the nTreg cell population was not sufficient to protect against lethal GvHD. In contrast, transfer of STAT3-deficient naive CD4(+) T cells increased FoxP3(+) Treg cells post-BMT and prevented lethality, suggesting that the consequence of STAT3 signaling may be greater for iTreg rather than nTreg cells during GvHD.
C1 [Laurence, Arian; O'Shea, John J.] NIAMSD, Mol Immunol & Inflammat Branch, Bethesda, MD 20892 USA.
[Amarnath, Shoba; Mariotti, Jacopo; Foley, Jason; Fowler, Daniel H.] NCI, Expt Transplantat & Immunol Branch, Bethesda, MD 20892 USA.
[Kim, Yong Chan] NIAID, Immunol Lab, Bethesda, MD 20892 USA.
[Eckhaus, Michael] NIH, Natl Ctr Res Resources, Bethesda, MD 20892 USA.
RP Laurence, A (reprint author), NIAMSD, Mol Immunol & Inflammat Branch, Bethesda, MD 20892 USA.
EM laurencea@mail.nih.gov
RI Laurence, Arian/A-8770-2009
OI Laurence, Arian/0000-0003-0942-8292
FU National Institute of Arthritis and Musculoskeletal and Skin Diseases;
Center for Cancer Research, NCI
FX We thank J. Simone, J. Lay, and W.G. Telford for flow cytometry support;
P. Muranski and N.P. Restifo for providing mice. This work was supported
by the Intramural Research programs of the National Institute of
Arthritis and Musculoskeletal and Skin Diseases and the Center for
Cancer Research, NCI.
NR 48
TC 79
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U1 0
U2 9
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1074-7613
J9 IMMUNITY
JI Immunity
PD AUG 24
PY 2012
VL 37
IS 2
BP 209
EP 222
DI 10.1016/j.immuni.2012.05.027
PG 14
WC Immunology
SC Immunology
GA 998SX
UT WOS:000308261800007
PM 22921119
ER
PT J
AU Tsuji, Y
Watanabe, T
Kudo, M
Arai, H
Strober, W
Chiba, T
AF Tsuji, Yoshihisa
Watanabe, Tomohiro
Kudo, Masatoshi
Arai, Hidenori
Strober, Warren
Chiba, Tsutomu
TI Sensing of Commensal Organisms by the Intracellular Sensor NOD1 Mediates
Experimental Pancreatitis
SO IMMUNITY
LA English
DT Article
ID MONOCYTE CHEMOATTRACTANT PROTEIN-1; ACINAR-CELLS; BACTERIAL
PEPTIDOGLYCAN; INTESTINAL HOMEOSTASIS; SIGNAL TRANSDUCER; T-CELLS;
ACTIVATION; MICE; INFLAMMATION; RECOGNITION
AB The intracellular sensor NOD1 has important host-defense functions relating to a variety of pathogens. Here, we showed that this molecule also participates in the induction of a noninfectious pancreatitis via its response to commensal organisms. Pancreatitis induced by high-dose cerulein (a cholecystokinin receptor agonist) administration depends on NOD1 stimulation by gut microflora. To analyze this NOD1 activity, we induced pancreatitis by simultaneous administration of a low dose of cerulein (that does not itself induce pancreatitis) and FK156, an activator of NOD1 that mimics the effect of gut bacteria that have breached the mucosal barrier. The pancreatitis was dependent on acinar cell production of the chemokine MCP-1 and the intrapancreatic influx of CCR2(+) inflammatory cells. Moreover, MCP-1 production involved activation of the transcription factors NF-kappa B and STAT3, each requiring complementary NOD1 and cerulein signaling. These studies indicate that gut commensals enable noninfectious pancreatic inflammation via NOD1 signaling in pancreatic acinar cells.
C1 [Tsuji, Yoshihisa; Watanabe, Tomohiro; Chiba, Tsutomu] Kyoto Univ, Grad Sch Med, Dept Gastroenterol & Hepatol, Kyoto 6068507, Japan.
[Watanabe, Tomohiro] Kyoto Univ, Grad Sch Med, Ctr Innovat Immunoregulat Technol & Therapeut, Kyoto 6068507, Japan.
[Arai, Hidenori] Kyoto Univ, Grad Sch Med, Dept Human Hlth Sci, Kyoto 6068507, Japan.
[Watanabe, Tomohiro; Strober, Warren] NIAID, Mucosal Immun Sect, Lab Host Def, NIH, Bethesda, MD 20852 USA.
[Kudo, Masatoshi] Kinki Univ, Sch Med, Dept Gastroenterol & Hepatol, Osaka 5898511, Japan.
RP Watanabe, T (reprint author), Kyoto Univ, Grad Sch Med, Dept Gastroenterol & Hepatol, Kyoto 6068507, Japan.
EM tmhrwtnb@kuhp.kyoto-u.ac.jp
OI Kudo, Masatoshi/0000-0002-4102-3474
FU Japan Society for the Promotion of Science [21590532, 21229009,
24229005, 24659363]; Takeda Science Foundation; Astellas Foundation for
Research on Metabolic Disorders; Yakult Bioscience Foundation; Cell
Science Research Foundation; Kato Memorial Trust for Nambyo Research;
Uehara Memorial Foundation; Mochida Memorial Foundation for Medical and
Pharmaceutical Research; National Institutes of Health
FX This work was supported by Grant-in-Aid for Scientific Research
(21590532, 21229009, 24229005, and 24659363) from Japan Society for the
Promotion of Science, Takeda Science Foundation, Astellas Foundation for
Research on Metabolic Disorders, Yakult Bioscience Foundation, Cell
Science Research Foundation, Kato Memorial Trust for Nambyo Research,
Uehara Memorial Foundation, Mochida Memorial Foundation for Medical and
Pharmaceutical Research, and the Intramural Research Program of the
National Institutes of Health. We would like to thank N. Asano for
critical reading of this manuscript and S. Ueno for thoughtful support
of our experiments.
NR 35
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Z9 20
U1 0
U2 10
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1074-7613
J9 IMMUNITY
JI Immunity
PD AUG 24
PY 2012
VL 37
IS 2
BP 326
EP 338
DI 10.1016/j.immuni.2012.05.024
PG 13
WC Immunology
SC Immunology
GA 998SX
UT WOS:000308261800016
PM 22902233
ER
PT J
AU Gerner, MY
Kastenmuller, W
Ifrim, I
Kabat, J
Germain, RN
AF Gerner, Michael Y.
Kastenmuller, Wolfgang
Ifrim, Ina
Kabat, Juraj
Germain, Ronald N.
TI Histo-Cytometry: A Method for Highly Multiplex Quantitative Tissue
Imaging Analysis Applied to Dendritic Cell Subset Microanatomy in Lymph
Nodes
SO IMMUNITY
LA English
DT Article
ID IN-VIVO; IMMUNE-SYSTEM; T-CELLS; LANGERHANS CELLS; TRANSGENIC MICE;
AFFERENT LYMPH; MARGINAL ZONE; MICROSCOPY; RECEPTOR; EXPRESSION
AB Flow cytometry allows highly quantitative analysis of complex dissociated populations at the cost of neglecting their tissue localization. In contrast, conventional microscopy methods provide spatial information, but visualization and quantification of cellular subsets defined by complex phenotypic marker combinations is challenging. Here, we describe an analytical microscopy method, "histo-cytometry," for visualizing and quantifying phenotypically complex cell populations directly in tissue sections. This technology is based on multiplexed antibody staining, tiled high-resolution confocal microscopy, voxel gating, volumetric cell rendering, and quantitative analysis. We have tested this technology on various innate and adaptive immune populations in murine lymph nodes (LNs) and were able to identify complex cellular subsets and phenotypes, achieving quantitatively similar results to flow cytometry, while also gathering cellular positional information. Here, we employ histo-cytometry to describe the spatial segregation of resident and migratory dendritic cell subsets into specialized microanatomical domains, suggesting an unexpected LN demarcation into discrete functional compartments.
C1 [Gerner, Michael Y.; Kastenmuller, Wolfgang; Ifrim, Ina; Germain, Ronald N.] NIAID, Lymphocyte Biol Sect, Lab Syst Biol, NIH, Bethesda, MD 20892 USA.
[Kabat, Juraj] NIAID, Biol Imaging Sect, Res Technol Branch, NIH, Bethesda, MD 20892 USA.
RP Gerner, MY (reprint author), NIAID, Lymphocyte Biol Sect, Lab Syst Biol, NIH, Bethesda, MD 20892 USA.
EM gernermy@niaid.nih.gov; rgermain@nih.gov
FU NIAID, NIH
FX Several individuals contributed to the development of this work. O.M.
Schwartz and S. Becker provided training and expertise for confocal
imaging. M. Roederer provided essential expertise in spillover
correction and data transformation for FlowJo-based analysis. D.H.
Kaplan and B.Z. Igyarto provided the (human-promoter)Langerin-Cre x
eYFP-flox mice and advice in migratory DC visualization. J. Schenkel
provided advice with antibody clone selection. T. Laemmerman and K.A.
Casey provided critical manuscript reviews and general project advice.
This work was supported by the Intramural Research Program of NIAID,
NIH.
NR 51
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U1 0
U2 18
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1074-7613
J9 IMMUNITY
JI Immunity
PD AUG 24
PY 2012
VL 37
IS 2
BP 364
EP 376
DI 10.1016/j.immuni.2012.07.011
PG 13
WC Immunology
SC Immunology
GA 998SX
UT WOS:000308261800019
PM 22863836
ER
PT J
AU Thorne, N
Shen, M
Lea, WA
Simeonov, A
Lovell, S
Auld, DS
Inglese, J
AF Thorne, Natasha
Shen, Min
Lea, Wendy A.
Simeonov, Anton
Lovell, Scott
Auld, Douglas S.
Inglese, James
TI Firefly Luciferase in Chemical Biology: A Compendium of Inhibitors,
Mechanistic Evaluation of Chemotypes, and Suggested Use As a Reporter
SO CHEMISTRY & BIOLOGY
LA English
DT Article
ID GENE ASSAYS; IDENTIFICATION; BIOLUMINESCENCE; CHEMISTRY; LIBRARIES;
PTC124; KINASE; CELLS
AB Firefly luciferase (FLuc) is frequently used as a reporter in high-throughput screening assays, owing to the exceptional sensitivity, dynamic range, and rapid measurement that bioluminescence affords. However, interaction of small molecules with FLuc has, to some extent, confounded its use in chemical biology and drug discovery. To identify and characterize chemotypes interacting with FLuc, we determined potency values for 360,864 compounds found in the NIH Molecular Libraries Small Molecule Repository, available in PubChem. FLuc inhibitory activity was observed for 12% of this library with discernible SAR. Characterization of 151 inhibitors demonstrated a variety of inhibition modes, including FLuc-catalyzed formation of multisubstrate adduct enzyme inhibitor complexes. As in some cell-based FLuc reporter assays, compounds acting as FLuc inhibitors yield paradoxical luminescence increases, thus data on compounds acquired from FLuc-dependent assays require careful analysis as described here.
C1 [Thorne, Natasha; Shen, Min; Lea, Wendy A.; Simeonov, Anton; Auld, Douglas S.; Inglese, James] Natl Ctr Advancing Translat Sci, Bethesda, MD 20892 USA.
[Inglese, James] Natl Human Genome Res Inst, NIH, Bethesda, MD 20892 USA.
[Lovell, Scott] Univ Kansas, Struct Biol Ctr, Lawrence, KS 66047 USA.
RP Auld, DS (reprint author), Novartis Inst Biomed Res, Cambridge, MA 02139 USA.
EM douglas.auld@novartis.com; jinglese@mail.nih.gov
FU Molecular Libraries Initiative of the National Institutes of Health
Roadmap for Medical Research [1 U54 MH084681-01]; National Human Genome
Research Institute, National Institutes of Health; Hauptman-Woodward
Medical Research Institute; U.S. Department of Energy, Office of
Science, Office of Basic Energy Sciences [DE-AC02-06CH11357]; National
Center for Research Resources [5P20RR017708-10]; National Institute of
General Medical Sciences from the National Institutes of Health [8 P20
GM103420-10]
FX We thank W. Leister and J. Bougie for their expert assistance with LC/MS
analysis, D.-T. Nguyen for maximum common structure analysis, R.
MacArthur for help in data mining, P. Shinn and D. van Leer for compound
management support, K. P. Battaile for X-ray data collection, and S.
Michael for his HTS expertise. This work was supported by the Molecular
Libraries Initiative of the National Institutes of Health Roadmap for
Medical Research (1 U54 MH084681-01) and the Intramural Research Program
of the National Human Genome Research Institute, National Institutes of
Health. Use of the IMCA-CAT beamline 17-ID at the Advanced Photon Source
was supported by the companies of the Industrial Macromolecular
Crystallography Association through a contract with Hauptman-Woodward
Medical Research Institute. Use of the Advanced Photon Source was
supported by the U.S. Department of Energy, Office of Science, Office of
Basic Energy Sciences, under Contract No. DE-AC02-06CH11357. Use of the
KU COBRE Protein Structure Laboratory was supported by grants from the
National Center for Research Resources (5P20RR017708-10) and the
National Institute of General Medical Sciences (8 P20 GM103420-10) from
the National Institutes of Health.
NR 33
TC 45
Z9 45
U1 1
U2 25
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1074-5521
J9 CHEM BIOL
JI Chem. Biol.
PD AUG 24
PY 2012
VL 19
IS 8
BP 1060
EP 1072
DI 10.1016/j.chembiol.2012.07.015
PG 13
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 011GH
UT WOS:000309152500018
PM 22921073
ER
PT J
AU Leboucher, GP
Tsai, YC
Yang, M
Shaw, KC
Zhou, M
Veenstra, TD
Glickman, MH
Weissman, AM
AF Leboucher, Guillaume P.
Tsai, Yien Che
Yang, Mei
Shaw, Kristin C.
Zhou, Ming
Veenstra, Timothy D.
Glickman, Michael H.
Weissman, Allan M.
TI Stress-Induced Phosphorylation and Proteasomal Degradation of Mitofusin
2 Facilitates Mitochondrial Fragmentation and Apoptosis
SO MOLECULAR CELL
LA English
DT Article
ID RETICULUM-ASSOCIATED DEGRADATION; DYNAMIN-RELATED PROTEIN-1; E3
UBIQUITIN LIGASE; ENDOPLASMIC-RETICULUM; STRUCTURAL BASIS; FUSION; MFN2;
BAX; ACTIVATION; FISSION
AB Mitochondria play central roles in integrating pro- and antiapoptotic stimuli, and JNK is well known to have roles in activating apoptotic pathways. We establish a critical link between stress-induced JNK activation, mitofusin 2, which is an essential component of the mitochondrial outer membrane fusion apparatus, and the ubiquitin-proteasome system (UPS). JNK phosphorylation of mitofusin 2 in response to cellular stress leads to recruitment of the ubiquitin ligase (E3) Huwe1/Mule/ARF-BP1/HectH9/E3Histone/Lasu1 to mitofusin 2, with the BH3 domain of Huwe1 implicated in this interaction. This results in ubiquitin-mediated proteasomal degradation of mitofusin 2, leading to mitochondrial fragmentation and enhanced apoptotic cell death. The stability of a non-phosphorylatable mitofusin 2 mutant is unaffected by stress and protective against apoptosis. Conversely, a mitofusin 2 phosphomimic is more rapidly degraded without cellular stress. These findings demonstrate how proximal signaling events can influence both mitochondrial dynamics and apoptosis through phosphorylation-stimulated degradation of the mitochondrial fusion machinery.
C1 [Leboucher, Guillaume P.; Tsai, Yien Che; Yang, Mei; Shaw, Kristin C.; Weissman, Allan M.] NCI, Lab Prot Dynam & Signaling, Ctr Canc Res, Frederick, MD 21702 USA.
[Leboucher, Guillaume P.; Glickman, Michael H.] Technion Israel Inst Technol, Dept Biol, IL-32000 Haifa, Israel.
[Zhou, Ming; Veenstra, Timothy D.] NCI, Lab Prote & Analyt Technol, Adv Technol Program, Sci Applicat Int Corp Frederick Inc, Frederick, MD 21702 USA.
RP Tsai, YC (reprint author), NCI, Lab Prot Dynam & Signaling, Ctr Canc Res, Frederick, MD 21702 USA.
EM tsaiyien@mail.nih.gov; weissmaa@mail.nih.gov
OI Tsai, Yien Che/0000-0001-9624-1092
FU National Cancer Institute (NCI); National Institutes of Health (NIH)
Intramural Research Program [NO1-CO-12400]; NCI Director's Innovation
Award; Michael J. Fox Foundation; USA-Israel Bi-National Science
Foundation
FX We thank Mickael Cohen, Gustavo Gutierrez, Antonio Iavorone, Anna
Lasorella, Stephen Lockett, Deborah Morrison, Daniel Flitt, Ze'ev Ronai,
and Thomas Turbyville for helpful discussions; Wei Gu, Gustavo
Gutierrez, J. Silvio Gutkind, Wu Ou, Ze'ev Ronai, and Xiaodong Wang for
invaluable reagents; and Stanley Lipkowitz and Daniel Stringer for
critical review of this manuscript. This work was supported by the
National Cancer Institute (NCI), National Institutes of Health (NIH)
Intramural Research Program and Contract NO1-CO-12400 (M.Z. and T.D.V.),
a NCI Director's Innovation Award (Y.C.T.), a grant from the Michael J.
Fox Foundation (A.M.W.), and a grant from the USA-Israel Bi-National
Science Foundation (A.M.W. and M.H.G.).
NR 62
TC 83
Z9 87
U1 1
U2 13
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1097-2765
J9 MOL CELL
JI Mol. Cell
PD AUG 24
PY 2012
VL 47
IS 4
BP 547
EP 557
DI 10.1016/j.molcel.2012.05.041
PG 11
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 996CH
UT WOS:000308061100007
PM 22748923
ER
PT J
AU Yoon, JH
Abdelmohsen, K
Srikantan, S
Yang, XL
Martindale, JL
De, S
Huarte, M
Zhan, M
Becker, KG
Gorospe, M
AF Yoon, Je-Hyun
Abdelmohsen, Kotb
Srikantan, Subramanya
Yang, Xiaoling
Martindale, Jennifer L.
De, Supriyo
Huarte, Maite
Zhan, Ming
Becker, Kevin G.
Gorospe, Myriam
TI LincRNA-p21 Suppresses Target mRNA Translation
SO MOLECULAR CELL
LA English
DT Article
ID BINDING PROTEIN HUR; LONG NONCODING RNAS; EXPRESSION; REPRESSION;
DISEASE
AB Mammalian long intergenic noncoding RNAs (lincRNAs) are best known for modulating transcription. Here we report a posttranscriptional function for lincRNA-p21 as a modulator of translation. Association of the RNA-binding protein HuR with lincRNA-p21 favored the recruitment of let-7/Ago2 to lincRNA-p21, leading to lower lincRNA-p21 stability. Under reduced HuR levels, lincRNA-p21 accumulated in human cervical carcinoma He La cells, increasing its association with JUNB and CTNNB1 mRNAs and selectively lowering their translation. With elevated HuR, lincRNA-p21 levels declined, which in turn derepressed JunB and beta-catenin translation and increased the levels of these proteins. We propose that HuR controls translation of a subset of target mRNAs by influencing lincRNA-p21 levels. Our findings uncover a role for lincRNA as a posttranscriptional inhibitor of translation.
C1 [Yoon, Je-Hyun; Abdelmohsen, Kotb; Srikantan, Subramanya; Yang, Xiaoling; Martindale, Jennifer L.; Gorospe, Myriam] NIA, Lab Mol Biol & Immunol, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
[De, Supriyo; Becker, Kevin G.] NIA, Res Resources Branch, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
[Huarte, Maite] Univ Navarra, CIMA, Dept Oncol, Pamplona 31008, Spain.
[Zhan, Ming] Methodist Hosp, Dept Syst Med & Bioengn, Res Inst, Houston, TX 77030 USA.
RP Gorospe, M (reprint author), NIA, Lab Mol Biol & Immunol, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
EM myriam-gorospe@nih.gov
RI Huarte, Maite/J-6903-2014;
OI Huarte, Maite/0000-0003-3753-6493; srikantan,
subramanya/0000-0003-1810-6519; abdelmohsen, Kotb/0000-0001-6240-5810;
De, Supriyo/0000-0002-2075-7655; Becker, Kevin/0000-0002-6794-6656
FU NIA-IRP, NIH; NIH [U54CA149169]
FX We thank D.L. Kontoyiannis, G.J. Hannon, N. Mukherjee, and J.D. Keene
for providing reagents and information. J.-H.Y., K.A., S.S., X.Y.,
J.L.M., S.D., K.G.B., and M.G. were supported by the NIA-IRP, NIH. M.Z.
was supported by NIH U54CA149169.
NR 29
TC 258
Z9 284
U1 3
U2 54
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1097-2765
J9 MOL CELL
JI Mol. Cell
PD AUG 24
PY 2012
VL 47
IS 4
BP 648
EP 655
DI 10.1016/j.molcel.2012.06.027
PG 8
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 996CH
UT WOS:000308061100015
PM 22841487
ER
PT J
AU De Pisapia, N
Sandrini, M
Braver, TS
Cattaneo, L
AF De Pisapia, Nicola
Sandrini, Marco
Braver, Todd S.
Cattaneo, Luigi
TI Integration in Working Memory: A Magnetic Stimulation Study on the Role
of Left Anterior Prefrontal Cortex
SO PLOS ONE
LA English
DT Article
ID BASAL GANGLIA; BRAIN; INVOLVEMENT; RETRIEVAL; FACILITATION;
NEUROSCIENCE; INFORMATION; RETENTION; COGNITION; CAPACITY
AB Integration is a fundamental working memory operation, requiring the insertion of information from one task into the execution of another concurrent task. Previous neuroimaging studies have suggested the involvement of left anterior prefrontal cortex (L-aPFC) in relation to working memory integration demands, increasing during presentation of information to be integrated (loading), throughout its maintenance during a secondary task, up to the integration step, and then decreasing afterward (unloading). Here we used short bursts of 5 Hz repetitive Transcranic Magnetic Stimulation (rTMS) to modulate L-aPFC activity and to assess its causal role in integration. During experimental blocks, rTMS was applied (N = 10) over L-aPFC or vertex (control site) at different time-points of a task involving integration of a preloaded digit into a sequence of arithmetical steps, and contrasted with a closely matched task without integration demand (segregation). When rTMS was applied during the loading phase, reaction times during secondary task were faster, without significant changes in error rates. RTMS instead worsened performance when applied during information unloading. In contrast, no effects were observed when rTMS was applied during the other phases of integration, or during the segregation condition. These results confirm the hypothesis that L-aPFC is causally and selectively involved in the integration of information in working memory. They additionally suggest that pre-integration loading and post-integration unloading of information involving this area may be active and resource-consuming processes.
C1 [De Pisapia, Nicola; Sandrini, Marco; Cattaneo, Luigi] Univ Trent, CIMeC Ctr Mind Brain Sci, Rovereto, TN, Italy.
[De Pisapia, Nicola] Univ Trent, DiSCoF Dept Cognit Sci & Educ, Rovereto, TN, Italy.
[Sandrini, Marco] Uniformed Serv Univ Hlth Sci, Henry M Jackson Fdn, Ctr Neurosci & Regenerat Med, Bethesda, MD 20814 USA.
[Sandrini, Marco] NINDS, Human Cort Physiol & Stroke Neuro Rehabil Sect, NIH, Bethesda, MD USA.
[Braver, Todd S.] Washington Univ, Dept Psychol, Cognit Control & Psychopathol CCP Lab, St Louis, MO 63130 USA.
RP De Pisapia, N (reprint author), Univ Trent, CIMeC Ctr Mind Brain Sci, Rovereto, TN, Italy.
EM nicola.depisapia@unitn.it
RI Sandrini, Marco/J-2276-2014;
OI Sandrini, Marco/0000-0002-1664-5722; Braver, Todd/0000-0002-2631-3393;
Cattaneo, Luigi/0000-0001-8905-7529; De Pisapia,
Nicola/0000-0002-1089-8841
FU Societa Scienze Mente Cervello (SMC)/Fondazione Cassa di Risparmio di
Trento e Rovereto; Provincia Autonoma di Trento
FX Study supported by the Societa Scienze Mente Cervello (SMC)/Fondazione
Cassa di Risparmio di Trento e Rovereto and by the Provincia Autonoma di
Trento. The funders had no role in study design, data collection and
analysis, decision to publish, or preparation of the manuscript.
NR 43
TC 5
Z9 5
U1 2
U2 10
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD AUG 24
PY 2012
VL 7
IS 8
AR e43731
DI 10.1371/journal.pone.0043731
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 998GM
UT WOS:000308225500087
PM 22937085
ER
PT J
AU Ledberg, A
Montagnini, A
Coppola, R
Bressler, SL
AF Ledberg, Anders
Montagnini, Anna
Coppola, Richard
Bressler, Steven L.
TI Reduced Variability of Ongoing and Evoked Cortical Activity Leads to
Improved Behavioral Performance
SO PLOS ONE
LA English
DT Article
ID VISUAL-CORTEX V1; CEREBRAL-CORTEX; PSYCHOPHYSICS TOOLBOX; RESPONSE
VARIABILITY; NEURAL ACTIVITY; STRIATE CORTEX; EYE-MOVEMENTS;
REACTION-TIME; AREA V4; ATTENTION
AB Sensory responses of the brain are known to be highly variable, but the origin and functional relevance of this variability have long remained enigmatic. Using the variable foreperiod of a visual discrimination task to assess variability in the primate cerebral cortex, we report that visual evoked response variability is not only tied to variability in ongoing cortical activity, but also predicts mean response time. We used cortical local field potentials, simultaneously recorded from widespread cortical areas, to gauge both ongoing and visually evoked activity. Trial-to-trial variability of sensory evoked responses was strongly modulated by foreperiod duration and correlated both with the cortical variability before stimulus onset as well as with response times. In a separate set of experiments we probed the relation between small saccadic eye movements, foreperiod duration and manual response times. The rate of eye movements was modulated by foreperiod duration and eye position variability was positively correlated with response times. Our results indicate that when the time of a sensory stimulus is predictable, reduction in cortical variability before the stimulus can improve normal behavioral function that depends on the stimulus.
C1 [Ledberg, Anders] Univ Pompeu Fabra, Ctr Brain & Cognit, Dept Informat & Commun Technol, Barcelona, Spain.
[Montagnini, Anna] Ctr Natl Rech Sci, Inst Neurosci Timone, Marseille, France.
[Montagnini, Anna] Aix Marseille Univ, Marseille, France.
[Coppola, Richard] NIMH, Clin Brain Disorders Branch, Bethesda, MD 20892 USA.
[Bressler, Steven L.] Florida Atlantic Univ, Ctr Complex Syst & Brain Sci, Dept Psychol, Boca Raton, FL 33431 USA.
RP Ledberg, A (reprint author), Univ Pompeu Fabra, Ctr Brain & Cognit, Dept Informat & Commun Technol, Barcelona, Spain.
EM anders.ledberg@gmail.com
OI Ledberg, Anders/0000-0003-3827-8721
FU European Union [269921]; Ramon y Cajal program from the Spanish
government
FX The research leading to these results has received funding from the
European Union Seventh Framework Programme (FP7/2007-2013) under grant
agreement no. 269921 (BrainScaleS). AL is supported by the Ramon y Cajal
program from the Spanish government. The funders had no role in study
design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 53
TC 6
Z9 6
U1 0
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 2012
VL 7
IS 8
AR e43166
DI 10.1371/journal.pone.0043166
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 998GM
UT WOS:000308225500033
PM 22937021
ER
PT J
AU Purdue, MP
Hofmann, JN
Colt, JS
Hoxha, M
Ruterbusch, JJ
Davis, FG
Rothman, N
Wacholder, S
Schwartz, KL
Baccarelli, A
Chow, WH
AF Purdue, Mark P.
Hofmann, Jonathan N.
Colt, Joanne S.
Hoxha, Mirjam
Ruterbusch, Julie J.
Davis, Faith G.
Rothman, Nathaniel
Wacholder, Sholom
Schwartz, Kendra L.
Baccarelli, Andrea
Chow, Wong-Ho
TI A Case-Control Study of Peripheral Blood Mitochondrial DNA Copy Number
and Risk of Renal Cell Carcinoma
SO PLOS ONE
LA English
DT Article
ID ACTIVATION; CANCER
AB Background: Low mitochondrial DNA (mtDNA) copy number is a common feature of renal cell carcinoma (RCC), and may influence tumor development. Results from a recent case-control study suggest that low mtDNA copy number in peripheral blood may be a marker for increased RCC risk. In an attempt to replicate that finding, we measured mtDNA copy number in peripheral blood DNA from a U. S. population-based case-control study of RCC.
Methodology/Principal Findings: Relative mtDNA copy number was measured in triplicate by a quantitative real-time PCR assay using DNA extracted from peripheral whole blood. Cases (n = 603) had significantly lower mtDNA copy number than controls (n = 603; medians 0.85, 0.91 respectively; P = 0.0001). In multiple logistic regression analyses, the lowest quartile of mtDNA copy number was associated with a 60% increase in RCC risk relative to the highest quartile (OR = 1.6, 95% CI = 1.1-2.2; P-trend = 0.009). This association remained in analyses restricted to cases treated by surgery alone (OR (Q1) = 1.4, 95% CI = 1.0-2.1) and to localized tumors (2.0, 1.3-2.8).
Conclusions/Significance: Our findings from this investigation, to our knowledge the largest of its kind, offer important confirmatory evidence that low mtDNA copy number is associated with increased RCC risk. Additional research is needed to assess whether the association is replicable in prospective studies.
C1 [Purdue, Mark P.; Hofmann, Jonathan N.; Colt, Joanne S.; Rothman, Nathaniel; Wacholder, Sholom; Chow, Wong-Ho] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Hoxha, Mirjam; Baccarelli, Andrea] Fdn IRCCS Ca Granda Osped Maggiore Policlin, Ctr Mol & Genet Epidemiol, Dept Prevent Med, Milan, Italy.
[Hoxha, Mirjam; Baccarelli, Andrea] Univ Milan, Dept Environm & Occupat Hlth, Milan, Italy.
[Ruterbusch, Julie J.] Wayne State Univ, Sch Med, Dept Family Med & Publ Hlth Sci, Detroit, MI USA.
[Ruterbusch, Julie J.] Wayne State Univ, Sch Med, Barbara Ann Karmanos Inst, Detroit, MI USA.
[Davis, Faith G.; Schwartz, Kendra L.] Univ Illinois, Sch Publ Hlth, Dept Epidemiol, Chicago, IL USA.
[Baccarelli, Andrea] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA.
RP Purdue, MP (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
EM purduem@mail.nih.gov
RI Purdue, Mark/C-9228-2016;
OI Purdue, Mark/0000-0003-1177-3108; Baccarelli, Andrea/0000-0002-3436-0640
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 and the National Cancer Institute. The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 14
TC 23
Z9 23
U1 1
U2 2
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD AUG 24
PY 2012
VL 7
IS 8
AR e43149
DI 10.1371/journal.pone.0043149
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 998GM
UT WOS:000308225500032
PM 22937019
ER
PT J
AU Zhan, M
Riordon, DR
Yan, B
Tarasova, YS
Bruweleit, S
Tarasov, KV
Li, RA
Wersto, RP
Boheler, KR
AF Zhan, Ming
Riordon, Daniel R.
Yan, Bin
Tarasova, Yelena S.
Bruweleit, Sarah
Tarasov, Kirill V.
Li, Ronald A.
Wersto, Robert P.
Boheler, Kenneth R.
TI The B-MYB Transcriptional Network Guides Cell Cycle Progression and Fate
Decisions to Sustain Self-Renewal and the Identity of Pluripotent Stem
Cells
SO PLOS ONE
LA English
DT Article
ID DEVELOPMENTAL REGULATORS; CHROMATIN STATE; MOUSE EMBRYOS; ES CELLS;
DIFFERENTIATION; POLYCOMB; GENES; PHOSPHORYLATION; METHYLATION; DNA
AB Embryonic stem cells (ESCs) are pluripotent and have unlimited self-renewal capacity. Although pluripotency and differentiation have been examined extensively, the mechanisms responsible for self-renewal are poorly understood and are believed to involve an unusual cell cycle, epigenetic regulators and pluripotency-promoting transcription factors. Here we show that B-MYB, a cell cycle regulated phosphoprotein and transcription factor critical to the formation of inner cell mass, is central to the transcriptional and co-regulatory networks that sustain normal cell cycle progression and self-renewal properties of ESCs. Phenotypically, B-MYB is robustly expressed in ESCs and induced pluripotent stem cells (iPSCs), and it is present predominantly in a hypo-phosphorylated state. Knockdown of B-MYB results in functional cell cycle abnormalities that involve S, G2 and M phases, and reduced expression of critical cell cycle regulators like ccnb1 and plk1. By conducting gene expression profiling on control and B-MYB deficient cells, ChIP-chip experiments, and integrative computational analyses, we unraveled a highly complex B-MYB-mediated transcriptional network that guides ESC self-renewal. The network encompasses critical regulators of all cell cycle phases and epigenetic regulators, pluripotency transcription factors, and differentiation determinants. B-MYB along with E2F1 and c-MYC preferentially co-regulate cell cycle target genes. B-MYB also co-targets genes regulated by OCT4, SOX2 and NANOG that are significantly associated with stem cell differentiation, embryonic development, and epigenetic control. Moreover, loss of B-MYB leads to a breakdown of the transcriptional hierarchy present in ESCs. These results coupled with functional studies demonstrate that B-MYB not only controls and accelerates cell cycle progression in ESCs it contributes to fate decisions and maintenance of pluripotent stem cell identity.
C1 [Zhan, Ming; Yan, Bin] NIA, Bioinformat Unit, NIH, Baltimore, MD 21224 USA.
[Riordon, Daniel R.; Tarasova, Yelena S.; Bruweleit, Sarah; Tarasov, Kirill V.; Boheler, Kenneth R.] NIA, Mol Cardiol & Stem Cell Unit, NIH, Baltimore, MD 21224 USA.
[Wersto, Robert P.] NIA, Flow Cytometry Unit, NIH, Baltimore, MD 21224 USA.
[Zhan, Ming] Cornell Univ, Weill Cornell Med Coll, Methodist Hosp, Res Inst, Houston, TX USA.
[Yan, Bin] Hong Kong Baptist Univ, Dept Biol, Hong Kong, Hong Kong, Peoples R China.
[Li, Ronald A.; Boheler, Kenneth R.] Univ Hong Kong, Stem Cell & Regenerat Med Consortium, LKS Fac Med, Hong Kong, Hong Kong, Peoples R China.
RP Zhan, M (reprint author), Cornell Univ, Weill Cornell Med Coll, Methodist Hosp, Res Inst, Houston, TX USA.
EM bohelerk@grc.nia.nih.gov
FU Intramural Research Program of the NIH, National Institute on Aging;
Boehringer Ingelheim Fonds, Foundation for Basic Research in Medicine
(Heidesheim, Germany)
FX This research was supported in by the Intramural Research Program of the
NIH, National Institute on Aging, and by a scholarship (SB) from
Boehringer Ingelheim Fonds, Foundation for Basic Research in Medicine
(Heidesheim, Germany). The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 77
TC 11
Z9 11
U1 1
U2 22
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 2012
VL 7
IS 8
AR e42350
DI 10.1371/journal.pone.0042350
PG 22
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 998GM
UT WOS:000308225500012
PM 22936984
ER
PT J
AU Mizuno, N
Varkey, J
Kegulian, NC
Hegde, BG
Cheng, NQ
Langen, R
Steven, AC
AF Mizuno, Naoko
Varkey, Jobin
Kegulian, Natalie C.
Hegde, Balachandra G.
Cheng, Naiqian
Langen, Ralf
Steven, Alasdair C.
TI Remodeling of Lipid Vesicles into Cylindrical Micelles by
alpha-Synuclein in an Extended alpha-Helical Conformation
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID TRANSMISSION ELECTRON-MICROSCOPY; FAMILIAL PARKINSONS-DISEASE; NEURONAL
DYSFUNCTION; INTERMEDIATE STRUCTURES; ALZHEIMERS-DISEASE; BROKEN HELIX;
IN-VITRO; BINDING; PROTEIN; CELLS
AB alpha-Synuclein (alpha S) is a protein with multiple conformations and interactions. Natively unfolded in solution, alpha S accumulates as amyloid in neurological tissue in Parkinson disease and interacts with membranes under both physiological and pathological conditions. Here, we used cryoelectron microscopy in conjunction with electron paramagnetic resonance (EPR) and other techniques to characterize the ability of alpha S to remodel vesicles. At molar ratios of 1: 5 to 1: 40 for protein/lipid (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoglycerol), large spherical vesicles are converted into cylindrical micelles similar to 50 angstrom in diameter. Other lipids of the same charge (negative) exhibit generally similar behavior, although bilayer tubes of 150-500 angstrom in width are also produced, depending on the lipid acyl chains. At higher protein/lipid ratios, discoid particles, 70-100 angstrom across, are formed. EPR data show that, on cylindrical micelles, alpha S adopts an extended amphipathic alpha-helical conformation, with its long axis aligned with the tube axis. The observed geometrical relationship between alpha S and the micelle suggests that the wedging of its long alpha-helix into the outer leaflet of a membrane may cause curvature and an anisotropic partition of lipids, leading to tube formation.
C1 [Mizuno, Naoko; Cheng, Naiqian; Steven, Alasdair C.] NIAMS, Struct Biol Lab, NIH, Bethesda, MD 20892 USA.
[Varkey, Jobin; Kegulian, Natalie C.; Hegde, Balachandra G.; Langen, Ralf] Univ So Calif, Zilkha Neurogenet Inst, Los Angeles, CA 90033 USA.
RP Mizuno, N (reprint author), Max Planck Inst Biochem, Klopferspitz 18, D-82152 Martinsried, Germany.
EM mizuno@biochem.mpg.de; langen@med.usc.edu; stevena@mail.nih.gov
FU National Institutes of Health [2 R01 GM063915]; Intramural Research
Program of NIAMS
FX This work was supported, in whole or in part, by National Institutes of
Health Grant 2 R01 GM063915 (to R. L.) and the Intramural Research
Program of NIAMS.
NR 71
TC 33
Z9 33
U1 4
U2 38
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD AUG 24
PY 2012
VL 287
IS 35
BP 29301
EP 29311
DI 10.1074/jbc.M112.365817
PG 11
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 999CO
UT WOS:000308286900010
PM 22767608
ER
PT J
AU Rostovtseva, TK
Gurnev, PA
Chen, MY
Bezrukov, SM
AF Rostovtseva, Tatiana K.
Gurnev, Philip A.
Chen, Meng-Yang
Bezrukov, Sergey M.
TI Membrane Lipid Composition Regulates Tubulin Interaction with
Mitochondrial Voltage-dependent Anion Channel
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID PHOSPHOLIPID-VESICLES; BIOLOGICAL-MEMBRANES; PROTEIN-INTERACTIONS;
PACKING STRESS; VDAC; APOPTOSIS; MICROTUBULES; CONDUCTANCE; CARDIOLIPIN;
PERSPECTIVE
AB Elucidating molecular mechanisms by which lipids regulate protein function within biological membranes is critical for understanding the many cellular processes. Recently, we have found that dimeric alpha beta-tubulin, a subunit of microtubules, regulates mitochondrial respiration by blocking the voltage-dependent anion channel (VDAC) of mitochondrial outer membrane. Here, we show that the mechanism of VDAC blockage by tubulin involves tubulin interaction with the membrane as a critical step. The on-rate of the blockage varies up to 100-fold depending on the particular lipid composition used for bilayer formation in reconstitution experiments and increases with the increasing content of dioleoylphosphatidylethanolamine (DOPE) in dioleoylphosphatidylcholine (DOPC) bilayers. At physiologically low salt concentrations, the on-rate is decreased by the charged lipid. The off-rate of VDAC blockage by tubulin does not depend on the lipid composition. Using confocal fluorescence microscopy, we compared tubulin binding to the membranes of giant unilamellar vesicles (GUVs) made from DOPC and DOPC/DOPE mixtures. We found that detectable binding of the fluorescently labeled dimeric tubulin to GUV membranes requires the presence of DOPE. We propose that prior to the characteristic blockage of VDAC, tubulin first binds to the membrane in a lipid-dependent manner. We thus reveal a new potent regulatory role of the mitochondrial lipids in control of the mitochondrial outer membrane permeability and hence mitochondrial respiration through tuning VDAC sensitivity to blockage by tubulin. More generally, our findings give an example of the lipid-controlled protein-protein interaction where the choice of lipid species is able to change the equilibrium binding constant by orders of magnitude.
C1 [Rostovtseva, Tatiana K.; Gurnev, Philip A.; Chen, Meng-Yang; Bezrukov, Sergey M.] Eunice Kennedy Shriver NICHD, Program Phys Biol, NIH, Bethesda, MD 20892 USA.
RP Rostovtseva, TK (reprint author), NICHD, NIH, 9000 Rockville Pike,Bldg 9,Rm 1E-106, Bethesda, MD 20892 USA.
EM rostovtt@mail.nih.gov
FU National Institutes of Health Intramural Research Program, Eunice
Kennedy Shriver NICHD
FX This work was supported, in whole or in part, by National Institutes of
Health Intramural Research Program, Eunice Kennedy Shriver NICHD.
NR 56
TC 20
Z9 20
U1 3
U2 16
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD AUG 24
PY 2012
VL 287
IS 35
BP 29589
EP 29598
DI 10.1074/jbc.M112.378778
PG 10
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 999CO
UT WOS:000308286900034
PM 22763701
ER
PT J
AU Laughton, B
Cornell, M
Grove, D
Kidd, M
Springer, PE
Dobbels, E
van Rensburg, AJ
Violari, A
Babiker, AG
Madhi, SA
Jean-Philippe, P
Gibb, DM
Cotton, MF
AF Laughton, Barbara
Cornell, Morna
Grove, Debbie
Kidd, Martin
Springer, Priscilla E.
Dobbels, Els
van Rensburg, Anita J.
Violari, Avy
Babiker, Abdel G.
Madhi, Shabir A.
Jean-Philippe, Patrick
Gibb, Diana M.
Cotton, Mark F.
TI Early antiretroviral therapy improves neurodevelopmental outcomes in
infants
SO AIDS
LA English
DT Article
DE early antiretroviral therapy; HIV; infants; neurodevelopment
ID PERINATAL HIV-INFECTION; CHILDREN; MANIFESTATIONS
AB Objectives: To evaluate the effect of early versus deferred antiretroviral therapy (ART) on the neurodevelopment of infants from Cape Town participating in the Children with HIV Early Antiretroviral Therapy (CHER) trial.
Design: HIV-infected infants were randomized to early (<3 months) or deferred ART. HIV-uninfected infants (HIV-exposed and HIV-unexposed) provide background data.
Methods: Neurological examination and Griffiths Mental Development Scales (GMDS) were administered between 10-16 months of age by testers blind to HIV status and randomized allocation. Mean quotients were compared using paired Student's t-tests.
Results: Sixty-four infants on early ART and 26 on deferred ART (of potential 77 and 38 respectively on CHER trial) were assessed at median age 11 months (range 10-16). On the GMDS, all scores were lower in the deferred arm and the General Griffiths and Locomotor Scores were significantly lower: mean (SD) = 100.1 (13.8) vs. 106.3 (10.6) P= 0.02; and 88.9 (16.3) vs. 97.7 (12.5), P < 0.01, respectively. Children with HIV who received early ART performed as well as children without HIV except on the Locomotor subscale. Both infected and uninfected mean GMDS scores were within the average range.
Conclusion: Infants initiated on early ART have significantly better Locomotor and general scores on the GMDS at median age 11 months compared to infants on deferred ART, despite careful monitoring and ready access to ART in the latter. (c) 2012 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins
C1 [Laughton, Barbara; Dobbels, Els; van Rensburg, Anita J.; Cotton, Mark F.] Univ Stellenbosch, Childrens Infect Dis Clin Res Unit, Dept Paediat & Child Hlth, Cape Town, South Africa.
[Laughton, Barbara; Springer, Priscilla E.; Dobbels, Els; van Rensburg, Anita J.; Cotton, Mark F.] Tygerberg Childrens Hosp, Cape Town, South Africa.
[Cornell, Morna] Univ Cape Town, Sch Publ Hlth & Family Med, Ctr Infect Dis Epidemiol & Res, ZA-7700 Rondebosch, South Africa.
[Grove, Debbie] Univ Stellenbosch, Dept Obstet & Gynaecol, Cape Town, South Africa.
[Kidd, Martin] Univ Stellenbosch, Ctr Stat Consultat, ZA-7600 Stellenbosch, South Africa.
[Violari, Avy] Univ Witwatersrand, Perinatal HIV Res Unit, Johannesburg, South Africa.
[Babiker, Abdel G.; Gibb, Diana M.] MRC, Clin Trials Unit, London, England.
[Madhi, Shabir A.] Univ Witwatersrand, Natl Res Fdn Vaccine Preventable Dis, Dept Sci & Technol, Johannesburg, South Africa.
[Jean-Philippe, Patrick] NIAID, Henry Jackson Fdn Div DAIDS HJF DAIDS, NIH, Bethesda, MD 20892 USA.
RP Laughton, B (reprint author), Univ Stellenbosch, Childrens Infect Dis Clin Res Unit, Dept Paediat & Child Hlth, Cape Town, South Africa.
EM BL2@sun.ac.za
RI Laughton, Barbara/Q-3496-2016;
OI Laughton, Barbara/0000-0001-7260-7723; Cornell,
Morna/0000-0001-7149-8799
FU MRC; US National Institute of Allergy and Infectious Diseases (NIAID)
through the CIPRA network [U19 AI53217]; Department of Health of the
Western Cape; Department of Health of the Gauteng; Departments of Health
of the South Africa; GlaxoSmithKline; Federal funds from the National
Institute of Allergy and Infectious Diseases, National Institutes of
Health, United States Department of Health and Human Services
[HHSN272200800014C]; Harry Crossley Foundation; South African Medical
Research Council (MRC)
FX Although the work was supported by the MRC, the d views and opinions
expressed are not those of the MRC but of the authors of the material
produced.; Support for this study was provided by the US National
Institute of Allergy and Infectious Diseases (NIAID) through the CIPRA
network, Grant U19 AI53217; the Departments of Health of the Western
Cape and Gauteng, South Africa; and GlaxoSmithKline. Additional support
was provided with Federal funds from the National Institute of Allergy
and Infectious Diseases, National Institutes of Health, United States
Department of Health and Human Services, under Contract No.
HHSN272200800014C.; This study was funded through grants from the Harry
Crossley Foundation and the South African Medical Research Council
(MRC).
NR 19
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PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0269-9370
J9 AIDS
JI Aids
PD AUG 24
PY 2012
VL 26
IS 13
BP 1685
EP 1690
DI 10.1097/QAD.0b013e328355d0ce
PG 6
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 989AH
UT WOS:000307532100012
PM 22614886
ER
PT J
AU Achhra, AC
Amin, J
Sabin, C
Chu, HT
Dunn, D
Kuller, LH
Kovacs, JA
Cooper, DA
Emery, S
Law, MG
AF Achhra, Amit C.
Amin, Janaki
Sabin, Caroline
Chu, Haitao
Dunn, David
Kuller, Lewis H.
Kovacs, Joseph A.
Cooper, David A.
Emery, Sean
Law, Matthew G.
CA INSIGHT ESPRIT Study Grp
SMART Study Grp
TI Reclassification of risk of death with the knowledge of D-dimer in a
cohort of treated HIV-infected individuals
SO AIDS
LA English
DT Article
DE biomarker; cohort analysis; D-dimer; HAART; HIV; net reclassification
improvement; prognosis; risk assessment
ID ROC CURVE; ANTIRETROVIRAL TREATMENT; CARDIOVASCULAR-DISEASE; MORTALITY;
PREDICTION; INFLAMMATION; BIOMARKERS; THERAPY; ADULTS; INTERLEUKIN-2
AB Objective: To evaluate the change in categories of risk of death by adding D-dimer to conventional mortality risk factors.
Design: Cohort study.
Methods: Data on HIV-infected participants receiving standard combination antiretroviral therapy in two clinical trials (Evaluation of Subcutaneous Proleukin in a Randomized International Trial and Strategic Management of antiretroviral therapy), who had baseline D-dimer measured, were randomly split into two equal training and a validation clatasets. A multivariable survival model was built using the training dataset and included only conventional mortality risk factors measured at baseline. D-dimer was added to create the comparison model. The level of reclassification of mortality risk, for those with at least 5-years of follow-up, was then assessed by tabulating mortality risk defined as low (<= 2% predicted rate), moderate (2-5%) or high (>5%). Reclassification analyses were then repeated on the validation dataset.
Results: The analysis population at baseline had a mean age of 43 years, median CD4(+) cell count of 535 cells/mu l (IQR: 420-712), and 83% had HIV RNA of at least 500 copies/ml. In the training dataset (n = 1946, 8939 person-years), there were 83 deaths at a rate of 0.93 per 100 person-years. Addition of D-dimer to the reference model resulted in 6% or fewer (P > 0.05) being correctly reassigned, either up or down, to a new risk category, in both, training and validation clatasets. The integrated discrimination improvement in training and validation datasets was 0.60% (P = 0.084) and 0.45% (P = 0.168), respectively.
Conclusion: In this relatively well population, at the given risk cutoffs, D-dimer appeared to only modestly improve the discernment of risk. Risk reclassification provides a method for assessing the clinical utility of biomarkers in HIV cohort studies. (c) 2012 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins
C1 [Achhra, Amit C.; Amin, Janaki; Cooper, David A.; Emery, Sean; Law, Matthew G.] Univ New S Wales, Kirby Inst Infect & Immun Soc, Sydney, NSW 2052, Australia.
[Sabin, Caroline] UCL, Res Dept Infect & Populat Hlth, London, England.
[Chu, Haitao] Univ Minnesota, Sch Publ Hlth, Div Biostat, Minneapolis, MN 55455 USA.
[Dunn, David] MRC, Clin Trials Unit, London, England.
[Kuller, Lewis H.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA.
[Kovacs, Joseph A.] NIH, Dept Crit Care Med, NIH Clin Ctr, Bethesda, MD 20892 USA.
RP Achhra, AC (reprint author), Univ New S Wales, Kirby Inst, Natl Ctr HIV Epidemiol & Clin Res, Sydney, NSW 2052, Australia.
EM aachhra@kirby.unsw.edu.au
RI Chu, Haitao /J-7576-2012; Emery, Sean/H-4920-2013;
OI Emery, Sean/0000-0001-6072-8309; Chu, Haitao/0000-0003-0932-598X
FU National Institute of Allergy and Infectious Diseases, National
Institutes of Health [U01AI46957, U01AI068641, U01AI042170, U01AI46362]
FX The study was funded by the National Institute of Allergy and Infectious
Diseases, National Institutes of Health [grant numbers: U01AI46957 and
U01AI068641 (ESPRIT); U01AI042170 and U01AI46362 (SMART)].
NR 42
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U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0269-9370
J9 AIDS
JI Aids
PD AUG 24
PY 2012
VL 26
IS 13
BP 1707
EP 1717
DI 10.1097/QAD.0b013e328355c1659
PG 11
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 989AH
UT WOS:000307532100014
PM 22614887
ER
PT J
AU Koonin, EV
AF Koonin, Eugene V.
TI Does the central dogma still stand?
SO BIOLOGY DIRECT
LA English
DT Article
ID DNA-SEQUENCE DIFFERENCES; MESSENGER-RNA DECAY; HUMAN TRANSCRIPTOME;
WIDESPREAD RNA; GENETIC-VARIATION; SACCHAROMYCES-CEREVISIAE;
ENVIRONMENTAL-STRESS; PRENATAL EXPOSURE; MOLECULAR-BIOLOGY; SCRAPIE
PRIONS
AB Prions are agents of analog, protein conformation-based inheritance that can confer beneficial phenotypes to cells, especially under stress. Combined with genetic variation, prion-mediated inheritance can be channeled into prion-independent genomic inheritance. Latest screening shows that prions are common, at least in fungi. Thus, there is non-negligible flow of information from proteins to the genome in modern cells, in a direct violation of the Central Dogma of molecular biology. The prion-mediated heredity that violates the Central Dogma appears to be a specific, most radical manifestation of the widespread assimilation of protein (epigenetic) variation into genetic variation. The epigenetic variation precedes and facilitates genetic adaptation through a general 'look-ahead effect' of phenotypic mutations. This direction of the information flow is likely to be one of the important routes of environment-genome interaction and could substantially contribute to the evolution of complex adaptive traits.
C1 Natl Inst Hlth, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA.
RP Koonin, EV (reprint author), Natl Inst Hlth, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA.
EM koonin@ncbi.nlm.nih.gov
FU US Department of Health and Human Services (National Library of
Medicine)
FX The author's research is supported by intramural funds of the US
Department of Health and Human Services (National Library of Medicine).
NR 93
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U1 7
U2 52
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1745-6150
J9 BIOL DIRECT
JI Biol. Direct
PD AUG 23
PY 2012
VL 7
AR 27
DI 10.1186/1745-6150-7-27
PG 7
WC Biology
SC Life Sciences & Biomedicine - Other Topics
GA 020NH
UT WOS:000309817600001
PM 22913395
ER
PT J
AU Kim, DS
Zhang, W
Millman, SE
Hwang, BJ
Kwon, SJ
Clayberger, C
Pagano, M
Krensky, AM
AF Kim, Dong Seok
Zhang, Wei
Millman, Scott E.
Hwang, Byung Joon
Kwon, Seok Joo
Clayberger, Carol
Pagano, Michele
Krensky, Alan M.
TI Fbw7 gamma-mediated degradation of KLF13 prevents RANTES expression in
resting human but not murine T lymphocytes
SO BLOOD
LA English
DT Article
ID E3 UBIQUITIN LIGASE; KRUPPEL-LIKE FACTOR; CYCLIN-E; IN-VIVO;
TRANSCRIPTION FACTOR; CHEMOKINE RANTES; CYTOKINE RANTES; ACTIVATION;
PROTEIN; CELLS
AB RANTES (CCL5) is a chemokine implicated in many human diseases. We previously showed that the transcription factor Kruppel-like factor 13 (KLF13) controls the late (3-5 days after activation) expression of RANTES in T lymphocytes and that KLF13 itself is translationally regulated through the 5'-untranslated region of its mRNA. Here, we show that KLF13 levels are further regulated by ubiquitination and degradation. KLF13 protein is undetectable in resting human T lymphocytes, but treatment with either proteosomal or lysosomal inhibitors increases KLF13 protein levels. Glycogen synthase kinase 3 beta (GSK3 beta)-mediated phosphorylation of KLF13 triggers the ubiquitination of KLF13 by the E3 ligase Fbw7 gamma, resulting in KLF13 protein degradation. Knock-down of either Fbw7 gamma or GSK3 beta by small interfering RNA increases KLF13 expression in resting human T lymphocytes. In contrast, in murine T lymphocytes, KLF13 protein is abundant because of the absence of Fbw7 gamma. Treatment of unactivated human lymphocytes with lysosomal inhibitors stabilizes KLF13 protein, resulting in an increase of RANTES mRNA and protein. Taken together, these studies found that tightly regulated control of both synthesis and degradation allows rapid changes in the level of KLF13 in human T lymphocytes. (Blood. 2012;120(8):1658-1667)
C1 [Kim, Dong Seok; Zhang, Wei; Hwang, Byung Joon; Kwon, Seok Joo; Clayberger, Carol; Krensky, Alan M.] NCI, Lab Cellular & Mol Biol, NIH, Bethesda, MD 20892 USA.
[Millman, Scott E.; Pagano, Michele] NYU, Sch Med, Inst Canc, New York, NY USA.
[Hwang, Byung Joon] Kangwon Natl Univ, Coll Biomed Sci, Dept Mol Biosci, Chunchon, South Korea.
[Pagano, Michele] NYU, Sch Med, Howard Hughes Med Inst, New York, NY USA.
RP Krensky, AM (reprint author), NCI, Lab Cellular & Mol Biol, NIH, Bethesda, MD 20892 USA.
EM krenskya@mail.nih.gov
RI zhang, wei/A-7015-2011;
OI pagano, michele/0000-0003-3210-2442
FU Intramural Research Program of the National Institutes of Health;
National Cancer Institute; Center for Cancer Research
FX This work was supported by the Intramural Research Program of the
National Institutes of Health, National Cancer Institute, and the Center
for Cancer Research.
NR 42
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U1 0
U2 3
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD AUG 23
PY 2012
VL 120
IS 8
BP 1658
EP 1667
DI 10.1182/blood-2012-03-415968
PG 10
WC Hematology
SC Hematology
GA 009DK
UT WOS:000309005600021
PM 22797700
ER
PT J
AU Chen, X
Sassano, MF
Zheng, LY
Setola, V
Chen, M
Bai, X
Frye, SV
Wetsel, WC
Roth, BL
Jin, J
AF Chen, Xin
Sassano, Maria F.
Zheng, Lianyou
Setola, Vincent
Chen, Meng
Bai, Xu
Frye, Stephen V.
Wetsel, William C.
Roth, Bryan L.
Jin, Jian
TI Structure-Functional Selectivity Relationship Studies of
beta-Arrestin-Biased Dopamine D-2 Receptor Agonists
SO JOURNAL OF MEDICINAL CHEMISTRY
LA English
DT Article
ID IN-VITRO; ANTIPSYCHOTIC EFFICACY; SIGNAL-TRANSDUCTION; SEROTONIN;
ARIPIPRAZOLE; LIGANDS; DERIVATIVES; ANTAGONISTS; ACTIVATION; BINDING
AB Functionally selective G protein-coupled receptor (GPCR) ligands, which differentially modulate canonical and noncanonical signaling, are extremely useful for elucidating key signal transduction pathways essential for both the therapeutic actions and side effects of drugs. However, few such ligands have been created, and very little purposeful attention has been devoted to studying what we term: "structure-functional selectivity relationships" (SFSR). We recently disclosed the first beta-arrestin-biased dopamine D-2 receptor (D2R) agonists UNC9975 (44) and UNC9994 (36), which have robust in vivo antipsychotic drug-like activities. Here we report the first comprehensive SFSR studies focused on exploring four regions of the aripiprazole scaffold, which resulted in the discovery of these beta-arrestin-biased D2R agonists. These studies provide a successful proof-of-concept for how functionally selective ligands can be discovered.
C1 [Chen, Xin; Zheng, Lianyou; Frye, Stephen V.; Jin, Jian] Univ N Carolina, Ctr Integrat Chem Biol & Drug Discovery, Div Chem Biol & Med Chem, UNC Eshelman Sch Pharm, Chapel Hill, NC 27599 USA.
[Sassano, Maria F.; Setola, Vincent; Roth, Bryan L.] Univ N Carolina, Sch Med, Dept Pharmacol, Chapel Hill, NC 27599 USA.
[Sassano, Maria F.; Setola, Vincent; Roth, Bryan L.] Univ N Carolina, Sch Med, Natl Inst Mental Hlth, Psychoact Drug Screening Program, Chapel Hill, NC 27599 USA.
[Zheng, Lianyou; Bai, Xu] Jilin Univ, Ctr Combinatorial Chem & Drug Discovery, Changchun 130012, Jilin, Peoples R China.
[Chen, Meng; Wetsel, William C.] Duke Univ, Dept Psychiat & Behav Sci, Med Ctr, Durham, NC 27710 USA.
[Chen, Meng; Wetsel, William C.] Duke Univ, Dept Cell Biol, Med Ctr, Durham, NC 27710 USA.
[Chen, Meng; Wetsel, William C.] Duke Univ, Dept Neurobiol, Med Ctr, Durham, NC 27710 USA.
RP Jin, J (reprint author), Univ N Carolina, Ctr Integrat Chem Biol & Drug Discovery, Div Chem Biol & Med Chem, UNC Eshelman Sch Pharm, Chapel Hill, NC 27599 USA.
EM bryan_roth@med.unc.edu; jianjin@unc.edu
RI sassano, maria/G-4941-2013; Roth, Bryan/F-3928-2010
FU NIH [U19MH082441S1, U19MH082441]
FX We thank the NIH (U19MH082441S1 and U19MH082441) for financial support
and Dr. Weihe Zhang for critical reading of synthetic procedures and
characterization data.
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PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0022-2623
J9 J MED CHEM
JI J. Med. Chem.
PD AUG 23
PY 2012
VL 55
IS 16
BP 7141
EP 7153
DI 10.1021/jm300603y
PG 13
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA 992BB
UT WOS:000307748800012
PM 22845053
ER
PT J
AU Browne, SK
Burbelo, PD
Chetchotisakd, P
Suputtamongkol, Y
Kiertiburanakul, S
Shaw, PA
Kirk, JL
Jutivorakool, K
Zaman, R
Ding, L
Hsu, AP
Patel, SY
Olivier, KN
Lulitanond, V
Mootsikapun, P
Anunnatsiri, S
Angkasekwinai, N
Sathapatayavongs, B
Hsueh, PR
Shieh, CC
Brown, MR
Thongnoppakhun, W
Claypool, R
Sampaio, EP
Thepthai, C
Waywa, D
Dacombe, C
Reizes, Y
Zelazny, AM
Saleeb, P
Rosen, LB
Mo, A
Iadarola, M
Holland, SM
AF Browne, Sarah K.
Burbelo, Peter D.
Chetchotisakd, Ploenchan
Suputtamongkol, Yupin
Kiertiburanakul, Sasisopin
Shaw, Pamela A.
Kirk, Jennifer L.
Jutivorakool, Kamonwan
Zaman, Rifat
Ding, Li
Hsu, Amy P.
Patel, Smita Y.
Olivier, Kenneth N.
Lulitanond, Viraphong
Mootsikapun, Piroon
Anunnatsiri, Siriluck
Angkasekwinai, Nasikarn
Sathapatayavongs, Boonmee
Hsueh, Po-Ren
Shieh, Chi-Chang
Brown, Margaret R.
Thongnoppakhun, Wanna
Claypool, Reginald
Sampaio, Elizabeth P.
Thepthai, Charin
Waywa, Duangdao
Dacombe, Camilla
Reizes, Yona
Zelazny, Adrian M.
Saleeb, Paul
Rosen, Lindsey B.
Mo, Allen
Iadarola, Michael
Holland, Steven M.
TI Adult-Onset Immunodeficiency in Thailand and Taiwan
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID NONTUBERCULOUS MYCOBACTERIAL INFECTION; INTERFERON-GAMMA AUTOANTIBODY;
IFN-GAMMA; AVIUM COMPLEX; PATIENT; DISEASES; SUSCEPTIBILITY; RECURRENT;
HIV
AB BACKGROUND
Autoantibodies against interferon-gamma are associated with severe disseminated opportunistic infection, but their importance and prevalence are unknown.
METHODS
We enrolled 203 persons from sites in Thailand and Taiwan in five groups: 52 patients with disseminated, rapidly or slowly growing, nontuberculous mycobacterial infection (group 1); 45 patients with another opportunistic infection, with or without nontuberculous mycobacterial infection (group 2); 9 patients with disseminated tuberculosis (group 3); 49 patients with pulmonary tuberculosis (group 4); and 48 healthy controls (group 5). Clinical histories were recorded, and blood specimens were obtained.
RESULTS
Patients in groups 1 and 2 had CD4+ T-lymphocyte counts that were similar to those in patients in groups 4 and 5, and they were not infected with the human immunodeficiency virus (HIV). Washed cells obtained from patients in groups 1 and 2 had intact cytokine production and a response to cytokine stimulation. In contrast, plasma obtained from these patients inhibited the activity of interferon-gamma in normal cells. High-titer anti-interferon-gamma autoantibodies were detected in 81% of patients in group 1, 96% of patients in group 2, 11% of patients in group 3, 2% of patients in group 4, and 2% of controls (group 5). Forty other anticytokine autoantibodies were assayed. One patient with cryptococcal meningitis had autoantibodies only against granulocyte-macrophage colony-stimulating factor. No other anticytokine autoantibodies or genetic defects correlated with infections. There was no familial clustering.
CONCLUSIONS
Neutralizing anti-interferon-gamma autoantibodies were detected in 88% of Asian adults with multiple opportunistic infections and were associated with an adult-onset immunodeficiency akin to that of advanced HIV infection. (Funded by the National Institute of Allergy and Infectious Diseases and the National Institute of Dental and Craniofacial Research; ClinicalTrials.gov number, NCT00814827.)
C1 [Browne, Sarah K.; Jutivorakool, Kamonwan; Zaman, Rifat; Ding, Li; Hsu, Amy P.; Olivier, Kenneth N.; Brown, Margaret R.; Claypool, Reginald; Sampaio, Elizabeth P.; Saleeb, Paul; Rosen, Lindsey B.; Mo, Allen; Holland, Steven M.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
[Shaw, Pamela A.; Kirk, Jennifer L.] NIAID, Biostat Res Branch, NIH, Bethesda, MD 20892 USA.
[Burbelo, Peter D.; Iadarola, Michael] Natl Inst Dent & Craniofacial Res, Lab Sensory Biol, NIH, Bethesda, MD USA.
[Zelazny, Adrian M.] NIH, Microbiol Serv, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA.
[Dacombe, Camilla; Reizes, Yona] Systex, Rockville, MD USA.
[Chetchotisakd, Ploenchan; Lulitanond, Viraphong; Mootsikapun, Piroon; Anunnatsiri, Siriluck] Khon Kaen Univ, Srinagarind Hosp, Khon Kaen, Thailand.
[Suputtamongkol, Yupin; Angkasekwinai, Nasikarn; Thongnoppakhun, Wanna; Thepthai, Charin; Waywa, Duangdao] Mahidol Univ, Siriraj Hosp, Bangkok 10700, Thailand.
[Browne, Sarah K.; Sathapatayavongs, Boonmee] Mahidol Univ, Ramathibodi Hosp, Fac Med, Bangkok 10400, Thailand.
[Jutivorakool, Kamonwan] Chulalongkorn Univ, Fac Med, Dept Med, Bangkok 10330, Thailand.
[Jutivorakool, Kamonwan] Thai Red Cross Soc, King Chulalongkorn Mem Hosp, Bangkok, Thailand.
[Patel, Smita Y.] Univ Oxford, John Radcliffe Hosp, Oxford OX3 9DU, England.
[Hsueh, Po-Ren] Natl Taiwan Univ, Taipei 10764, Taiwan.
[Shieh, Chi-Chang] Natl Cheng Kung Univ, Tainan 70101, Taiwan.
[Sampaio, Elizabeth P.] Inst Oswaldo Cruz, Leprosy Lab, BR-20001 Rio De Janeiro, Brazil.
[Mo, Allen] Colgate Univ, Hamilton, NY 13346 USA.
RP Browne, SK (reprint author), CRC B3-4141,MSC 1684,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM brownesa@niaid.nih.gov
OI HSUEH, PO-REN/0000-0002-7502-9225
FU Division of Intramural Research, National Institute of Allergy and
Infectious Diseases; Division of Intramural Research, National Institute
of Dental and Craniofacial Research, National Institutes of Health;
National Institute of Allergy and Infectious Diseases; National
Institute of Dental and Craniofacial Research
FX Supported by the Division of Intramural Research, National Institute of
Allergy and Infectious Diseases, and the Division of Intramural
Research, National Institute of Dental and Craniofacial Research,
National Institutes of Health.; Funded by the National Institute of
Allergy and Infectious Diseases and the National Institute of Dental and
Craniofacial Research
NR 30
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Z9 119
U1 2
U2 12
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD AUG 23
PY 2012
VL 367
IS 8
BP 725
EP 734
DI 10.1056/NEJMoa1111160
PG 10
WC Medicine, General & Internal
SC General & Internal Medicine
GA 992CX
UT WOS:000307754200007
PM 22913682
ER
PT J
AU Gregory, AP
Dendrou, CA
Attfield, KE
Haghikia, A
Xifara, DK
Butter, F
Poschmann, G
Kaur, G
Lambert, L
Leach, OA
Promel, S
Punwani, D
Felce, JH
Davis, SJ
Gold, R
Nielsen, FC
Siegel, RM
Mann, M
Bell, JI
McVean, G
Fugger, L
AF Gregory, Adam P.
Dendrou, Calliope A.
Attfield, Kathrine E.
Haghikia, Aiden
Xifara, Dionysia K.
Butter, Falk
Poschmann, Gereon
Kaur, Gurman
Lambert, Lydia
Leach, Oliver A.
Proemel, Simone
Punwani, Divya
Felce, James H.
Davis, Simon J.
Gold, Ralf
Nielsen, Finn C.
Siegel, Richard M.
Mann, Matthias
Bell, John I.
McVean, Gil
Fugger, Lars
TI TNF receptor 1 genetic risk mirrors outcome of anti-TNF therapy in
multiple sclerosis
SO NATURE
LA English
DT Article
ID TUMOR-NECROSIS-FACTOR; GENOME-WIDE ASSOCIATION; EXPERIMENTAL AUTOIMMUNE
ENCEPHALOMYELITIS; RESONANCE ENERGY-TRANSFER; SUSCEPTIBILITY LOCI;
DISEASE SUSCEPTIBILITY; METAANALYSIS; DEMYELINATION; INHIBITION;
MECHANISMS
AB Although there has been much success in identifying genetic variants associated with common diseases using genome-wide association studies (GWAS)(1), it has been difficult to demonstrate which variants are causal and what role they have in disease. Moreover, the modest contribution that these variants make to disease risk has raised questions regarding their medical relevance(2). Here we have investigated a single nucleotide polymorphism (SNP) in the TNFRSF1A gene, that encodes tumour necrosis factor receptor 1 (TNFR1), which was discovered through GWAS to be associated with multiple sclerosis (MS)(3,4), but not with other autoimmune conditions such as rheumatoid arthritis(5), psoriasis(6) and Crohn's disease(7). By analysing MS GWAS(3,4) data in conjunction with the 1000 Genomes Project data(8) we provide genetic evidence that strongly implicates this SNP, rs1800693, as the causal variant in the TNFRSF1A region. We further substantiate this through functional studies showing that the MS risk allele directs expression of a novel, soluble form of TNFR1 that can block TNF. Importantly, TNF-blocking drugs can promote onset or exacerbation of MS9-11, but they have proven highly efficacious in the treatment of autoimmune diseases for which there is no association with rs1800693. This indicates that the clinical experience with these drugs parallels the disease association of rs1800693, and that the MS-associated TNFR1 variant mimics the effect of TNF-blocking drugs. Hence, our study demonstrates that clinical practice can be informed by comparing GWAS across common autoimmune diseases and by investigating the functional consequences of the disease-associated genetic variation.
C1 [Gregory, Adam P.; Kaur, Gurman; Punwani, Divya; Felce, James H.; Davis, Simon J.; Fugger, Lars] Univ Oxford, Weatherall Inst Mol Med, John Radcliffe Hosp, MRC Human Immunol Unit, Oxford OX3 9DS, England.
[Dendrou, Calliope A.; Attfield, Kathrine E.; Haghikia, Aiden; Lambert, Lydia; Leach, Oliver A.; Proemel, Simone; Fugger, Lars] Univ Oxford, John Radcliffe Hosp, Div Clin Neurol, Nuffield Dept Clin Neurosci, Oxford OX3 9DS, England.
[Haghikia, Aiden; Gold, Ralf] Ruhr Univ Bochum, St Josef Hosp Bochum, Dept Neurol, D-44791 Bochum, Germany.
[Xifara, Dionysia K.; McVean, Gil] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England.
[Butter, Falk; Mann, Matthias] Max Planck Inst Biochem, Dept Prote & Signal Transduct, D-82152 Martinsried, Germany.
[Poschmann, Gereon] Univ Dusseldorf, Biol Med Forschungszentrum, Mol Prote Lab, D-40225 Dusseldorf, Germany.
[Nielsen, Finn C.] Univ Copenhagen, Rigshosp, Ctr Genom Med, DK-2100 Copenhagen O, Denmark.
[Siegel, Richard M.] NIAMSD, Immunoregulat Sect, Autoimmun Branch, NIH, Bethesda, MD 20892 USA.
[Bell, John I.] Univ Oxford, Oxford OX3 7DG, England.
[Fugger, Lars] Skejby Sygehus, Aarhus Univ Hosp, Inst Clin, DK-8200 Aarhus N, Denmark.
RP Fugger, L (reprint author), Univ Oxford, Weatherall Inst Mol Med, John Radcliffe Hosp, MRC Human Immunol Unit, Oxford OX3 9DS, England.
EM lars.fugger@imm.ox.ac.uk
RI Mann, Matthias/A-3454-2013;
OI Mann, Matthias/0000-0003-1292-4799; McVean, Gil/0000-0002-5012-4162;
Felce, James/0000-0001-5531-9244; Dendrou, Calliope/0000-0003-1179-4021;
Butter, Falk/0000-0002-7197-7279
FU UK Medical Research Council (MRC); European Union [FP7/2007-2013]; Naomi
Bramson Trust; Wellcome Trust [090532/Z/09/Z, 086084/Z/08/Z]; MRC;
Deutsche Forschungsgemeinschaft; Christopher Welch Scholarship; MS
Society; Dorothy Hodgkin Postgraduate Award
FX We thank the volunteers who donated blood samples, the IMSGC and WTCCC2
for data access, A. Auton for help with association analysis data
preparation, G. R. Screaton for providing TNFR1 constructs, and A.
Vincent and N. Willcox for critical reading of the manuscript. Work in
the authors' laboratories is supported by the UK Medical Research
Council (MRC), the European Union through grant FP7/2007-2013 (SYBILLA),
the Naomi Bramson Trust (L.F.), and the Wellcome Trust (090532/Z/09/Z
and 086084/Z/08/Z; G.M.). A.P.G., A.H., L.L., O.A.L. and D.P. are
supported by an MRC studentship, the Deutsche Forschungsgemeinschaft, a
Christopher Welch Scholarship, funding from the MRC and the MS Society,
and a Dorothy Hodgkin Postgraduate Award, respectively.
NR 30
TC 131
Z9 133
U1 2
U2 58
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
J9 NATURE
JI Nature
PD AUG 23
PY 2012
VL 488
IS 7412
BP 508
EP +
DI 10.1038/nature11307
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 992FS
UT WOS:000307761600036
PM 22801493
ER
PT J
AU Bousema, T
Dinglasan, RR
Morlais, I
Gouagna, LC
van Warmerdam, T
Awono-Ambene, PH
Bonnet, S
Diallo, M
Coulibaly, M
Tchuinkam, T
Mulder, B
Targett, G
Drakeley, C
Sutherland, C
Robert, V
Doumbo, O
Toure, Y
Graves, PM
Roeffen, W
Sauerwein, R
Birkett, A
Locke, E
Morin, M
Wu, YM
Churcher, TS
AF Bousema, Teun
Dinglasan, Rhoel R.
Morlais, Isabelle
Gouagna, Louis C.
van Warmerdam, Travis
Awono-Ambene, Parfait H.
Bonnet, Sarah
Diallo, Mouctar
Coulibaly, Mamadou
Tchuinkam, Timoleon
Mulder, Bert
Targett, Geoff
Drakeley, Chris
Sutherland, Colin
Robert, Vincent
Doumbo, Ogobara
Toure, Yeya
Graves, Patricia M.
Roeffen, Will
Sauerwein, Robert
Birkett, Ashley
Locke, Emily
Morin, Merribeth
Wu, Yimin
Churcher, Thomas S.
TI Mosquito Feeding Assays to Determine the Infectiousness of Naturally
Infected Plasmodium falciparum Gametocyte Carriers
SO PLOS ONE
LA English
DT Article
ID TRANSMISSION-BLOCKING IMMUNITY; ANOPHELES-GAMBIAE; MALARIA TRANSMISSION;
WESTERN KENYA; SEX-RATIO; INFECTIVITY; REDUCTION; CAMEROON; HOST;
PYRIMETHAMINE
AB Introduction: In the era of malaria elimination and eradication, drug-based and vaccine-based approaches to reduce malaria transmission are receiving greater attention. Such interventions require assays that reliably measure the transmission of Plasmodium from humans to Anopheles mosquitoes.
Methods: We compared two commonly used mosquito feeding assay procedures: direct skin feeding assays and membrane feeding assays. Three conditions under which membrane feeding assays are performed were examined: assays with i) whole blood, ii) blood pellets resuspended with autologous plasma of the gametocyte carrier, and iii) blood pellets resuspended with heterologous control serum.
Results: 930 transmission experiments from Cameroon, The Gambia, Mali and Senegal were included in the analyses. Direct skin feeding assays resulted in higher mosquito infection rates compared to membrane feeding assays (odds ratio 2.39, 95% confidence interval 1.94-2.95) with evident heterogeneity between studies. Mosquito infection rates in membrane feeding assays and direct skin feeding assays were strongly correlated (p < 0.0001). Replacing the plasma of the gametocyte donor with malaria naive control serum resulted in higher mosquito infection rates compared to own plasma (OR 1.92, 95% CI 1.68-2.19) while the infectiousness of gametocytes may be reduced during the replacement procedure (OR 0.60, 95% CI 0.52-0.70).
Conclusions: Despite a higher efficiency of direct skin feeding assays, membrane feeding assays appear suitable tools to compare the infectiousness between individuals and to evaluate transmission-reducing interventions. Several aspects of membrane feeding procedures currently lack standardization; this variability makes comparisons between laboratories challenging and should be addressed to facilitate future testing of transmission-reducing interventions.
C1 [Bousema, Teun; Targett, Geoff; Drakeley, Chris; Sutherland, Colin] London Sch Hyg & Trop Med, Dept Immun & Infect, London WC1, England.
[Bousema, Teun; Roeffen, Will; Sauerwein, Robert] Radboud Univ Nijmegen, Med Ctr, Dept Med Microbiol, NL-6525 ED Nijmegen, Netherlands.
[Dinglasan, Rhoel R.; van Warmerdam, Travis] Johns Hopkins Bloomberg Sch Publ Hlth, W Harry Feinstone Dept Mol Microbiol & Immunol, Baltimore, MD USA.
[Dinglasan, Rhoel R.; van Warmerdam, Travis] Malaria Res Inst, Baltimore, MD USA.
[Morlais, Isabelle; Awono-Ambene, Parfait H.; Tchuinkam, Timoleon] Inst Rech Dev, Org Coordinat Lutte Endemies Afrique Cent OCEAC, Lab Rech Paludisme, Yaounde, Cameroon.
[Morlais, Isabelle; Gouagna, Louis C.; Robert, Vincent] Inst Rech Dev, MIVEGEC, Montpellier, France.
[Bonnet, Sarah] Agence Natl Secur Sanit, USC INRA Bartonella Tiques, Maisons Alfort, France.
[Diallo, Mouctar; Coulibaly, Mamadou; Doumbo, Ogobara; Toure, Yeya] Univ Sci Tech & Technol, Malaria Res & Training Ctr, Bamako, Mali.
[Tchuinkam, Timoleon] Univ Dschang, Lab Appl Biol & Ecol, Malaria Res Unit, Dschang, Cameroon.
[Mulder, Bert] Microbiol Lab Twente, Dept Med Microbiol, Enschede, Netherlands.
[Graves, Patricia M.] James Cook Univ, Sch Publ Hlth Trop Med & Rehabil Sci, Cairns, Qld, Australia.
[Birkett, Ashley; Locke, Emily; Morin, Merribeth] PATH Malaria Vaccine Initiat, Washington, DC USA.
[Wu, Yimin] NIAID, Lab Malaria Immunol & Vaccinol, Rockville, MD USA.
[Churcher, Thomas S.] Univ London Imperial Coll Sci Technol & Med, Infect Dis Epidemiol MRC Ctr Outbreak Anal & Mode, London, England.
RP Bousema, T (reprint author), London Sch Hyg & Trop Med, Dept Immun & Infect, London WC1, England.
EM teun.bousema@lshtm.ac.uk
RI Sauerwein, Robert/C-8519-2013; Morlais, Isabelle/F-5078-2014; Graves,
Patricia/J-8691-2014; Roeffen, W.F.G./L-4607-2015; Bousema,
Teun/N-3574-2014;
OI Morlais, Isabelle/0000-0002-2962-7670; Sutherland,
Colin/0000-0003-1592-6407; Graves, Patricia/0000-0002-5215-3901;
Dinglasan, Rhoel/0000-0001-5433-8179; Dinglasan,
Rhoel/0000-0001-6563-1506; Churcher, Thomas/0000-0002-8442-0525
FU Bill & Melinda Gates Foundation; European FP7 framework (REDMAL)
[242079]; PATH Malaria Vaccine Initiative (MVI); MVI; Bloomberg Family
Foundation; Johns Hopkins Malaria Research Institute; Institut de
Recherche pour le Developpement; TMRC; NIAID/NIH; Division of Intramural
Research, National Institute of Allergy and Infectious Diseases;
Imperial College London; EC FP7 Collaborative project TransMalariaBloc
[HEALTH-F3-2008-223736]
FX The work of TB is supported by grants from the Bill & Melinda Gates
Foundation and the European FP7 framework (REDMAL project, # 242079) and
the PATH Malaria Vaccine Initiative (MVI). RRD and TW were supported by
MVI, the Bloomberg Family Foundation and the Johns Hopkins Malaria
Research Institute. IM, LCG, PHAA, SB and VR were partly supported by
the Institut de Recherche pour le Developpement. The MRTC group in Mali
is supported by extramural (TMRC) and intramural grants from NIAID/NIH.
YW is supported by Division of Intramural Research, National Institute
of Allergy and Infectious Diseases. TSC is supported by a Junior
Research Fellowship from Imperial College London and an EC FP7
Collaborative project TransMalariaBloc (HEALTH-F3-2008-223736). The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 63
TC 58
Z9 58
U1 2
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 22
PY 2012
VL 7
IS 8
AR e42821
DI 10.1371/journal.pone.0042821
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 999CI
UT WOS:000308286300026
PM 22936993
ER
PT J
AU Mancini, M
Salarian, A
Carlson-Kuhta, P
Zampieri, C
King, L
Chiari, L
Horak, FB
AF Mancini, Martina
Salarian, Arash
Carlson-Kuhta, Patricia
Zampieri, Cris
King, Laurie
Chiari, Lorenzo
Horak, Fay B.
TI ISway: a sensitive, valid and reliable measure of postural control
SO JOURNAL OF NEUROENGINEERING AND REHABILITATION
LA English
DT Article
DE Postural control; Accelerometers; Inertial sensors; Parkinson's disease
ID DEEP BRAIN-STIMULATION; PARKINSONS-DISEASE; TRUNK ACCELEROMETRY;
SPONTANEOUS-SWAY; BALANCE; INSTABILITY; GAIT; RELIABILITY; WALKING;
STANCE
AB Background: Clinicians need a practical, objective test of postural control that is sensitive to mild neurological disease, shows experimental and clinical validity, and has good test-retest reliability. We developed an instrumented test of postural sway (ISway) using a body-worn accelerometer to offer an objective and practical measure of postural control.
Methods: We conducted two separate studies with two groups of subjects. Study I: sensitivity and experimental concurrent validity. Thirteen subjects with early, untreated Parkinson's disease (PD) and 12 age-matched control subjects (CTR) were tested in the laboratory, to compare sway from force-plate COP and inertial sensors. Study II: test-retest reliability and clinical concurrent validity. A different set of 17 early-to-moderate, treated PD (tested ON medication), and 17 age-matched CTR subjects were tested in the clinic to compare clinical balance tests with sway from inertial sensors. For reliability, the sensor was removed, subjects rested for 30 min, and the protocol was repeated. Thirteen sway measures (7 time-domain, 5 frequency-domain measures, and JERK) were computed from the 2D time series acceleration (ACC) data to determine the best metrics for a clinical balance test.
Results: Both center of pressure (COP) and ACC measures differentiated sway between CTR and untreated PD. JERK and time-domain measures showed the best test-retest reliability (JERK ICC was 0.86 in PD and 0.87 in CTR; time-domain measures ICC ranged from 0.55 to 0.84 in PD and from 0.60 to 0.89 in CTR). JERK, all but one time-domain measure, and one frequency measure were significantly correlated with the clinical postural stability score (r ranged from 0.50 to 0.63, 0.01 < p < 0.05).
Conclusions: Based on these results, we recommend a subset of the most sensitive, reliable, and valid ISway measures to characterize posture control in PD: 1) JERK, 2) RMS amplitude and mean velocity from the time-domain measures, and 3) centroidal frequency as the best frequency measure, as valid and reliable measures of balance control from ISway.
C1 [Mancini, Martina; Salarian, Arash; Carlson-Kuhta, Patricia; King, Laurie; Horak, Fay B.] Oregon Hlth & Sci Univ, Dept Neurol, Sch Med, Beaverton, OR 97006 USA.
[Mancini, Martina; Chiari, Lorenzo] Alma Mater Studiorum Univ Bologna, Biomed Engn Unit, Dept Elect Comp Sci & Syst, I-40136 Bologna, Italy.
[Zampieri, Cris] NIH, Funct & Appl Biomech Lab, Dept Rehabil Med, Ctr Clin, Bethesda, MD 20892 USA.
RP Mancini, M (reprint author), Oregon Hlth & Sci Univ, Dept Neurol, Sch Med, 505 NW 185th Ave, Beaverton, OR 97006 USA.
EM mancinim@ohsu.edu
RI Salarian, Arash/E-8311-2016;
OI Salarian, Arash/0000-0001-7332-0062; Chiari, Lorenzo/0000-0002-2318-4370
FU Kinetics Foundation; NIH [RC1 NS068678, R37 AG006457]; Intramural
Research Program of the NIH, Clinical Center, Rehabilitation Medicine
Department
FX We thank Kelsey Priest and Triana Nagel for scheduling and testing
subjects. This publication was made possible with support from Kinetics
Foundation, NIH grants RC1 NS068678 and R37 AG006457, and in part by the
Intramural Research Program of the NIH, Clinical Center, Rehabilitation
Medicine Department.
NR 44
TC 68
Z9 71
U1 3
U2 34
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1743-0003
J9 J NEUROENG REHABIL
JI J. NeuroEng. Rehabil.
PD AUG 22
PY 2012
VL 9
AR 59
DI 10.1186/1743-0003-9-59
PG 8
WC Engineering, Biomedical; Neurosciences; Rehabilitation
SC Engineering; Neurosciences & Neurology; Rehabilitation
GA 026IW
UT WOS:000310270000001
PM 22913719
ER
PT J
AU Suzuki, N
Fukushi, M
Kosaki, K
Doyle, AD
de Vega, S
Yoshizaki, K
Akazawa, C
Arikawa-Hirasawa, E
Yamada, Y
AF Suzuki, Nobuharu
Fukushi, Masaya
Kosaki, Keisuke
Doyle, Andrew D.
de Vega, Susana
Yoshizaki, Keigo
Akazawa, Chihiro
Arikawa-Hirasawa, Eri
Yamada, Yoshihiko
TI Teneurin-4 Is a Novel Regulator of Oligodendrocyte Differentiation and
Myelination of Small-Diameter Axons in the CNS
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
ID FOCAL ADHESION KINASE; CENTRAL-NERVOUS-SYSTEM; BRAIN; MOUSE; GENES;
ASTROCYTES; OUTGROWTH
AB Myelination is essential for proper functioning of the CNS. In this study, we have identified a mouse mutation, designated furue, which causes tremors and hypomyelination in the CNS, particularly in the spinal cord, but not in the sciatic nerve of the PNS. In the spinal cord of the furue mice, myelination of small-diameter axons was dramatically reduced, and differentiation of oligodendrocytes, the myelin-forming cells in the CNS, was inhibited. We subsequently found that the furue mutation was associated with a transgene insertion into the teneurin-4 (Ten-4, Ten-m4/Odz4) gene, encoding a transmembrane protein of unknown function. Ten-4 was strongly expressed in the spinal cord of wild-type mice and was induced during normal oligodendrocyte differentiation. In contrast, in the furue mice, the expression of Ten-4 was absent. Differentiation and cellular process formation of oligodendrocytes were inhibited in primary cell culture from the furue mice. Cell differentiation and process formation were also inhibited in the oligodendrocyte progenitor cell line CG-4 after suppression of Ten-4 expression by shRNA. Furthermore, Ten-4 positively regulated focal adhesion kinase, an essential signaling molecule for oligodendrocyte process formation and myelination of small-diameter axons. These findings suggest that Ten-4 is a novel regulator of oligodendrocyte differentiation and that it plays a critical role in the myelination of small-diameter axons in the CNS.
C1 [Suzuki, Nobuharu; Fukushi, Masaya; Kosaki, Keisuke; Doyle, Andrew D.; de Vega, Susana; Yoshizaki, Keigo; Yamada, Yoshihiko] Natl Inst Dent & Craniofacial Res, Lab Cell & Dev Biol, NIH, Bethesda, MD 20814 USA.
[Suzuki, Nobuharu; Akazawa, Chihiro] Tokyo Med & Dent Univ, Dept Biochem & Biophys, Grad Sch Hlth Care Sci, Tokyo 1138510, Japan.
[de Vega, Susana; Arikawa-Hirasawa, Eri] Juntendo Univ, Res Inst Dis Old Age, Fac Med, Tokyo 1138421, Japan.
[de Vega, Susana; Arikawa-Hirasawa, Eri] Juntendo Univ, Dept Neurol, Fac Med, Tokyo 1138421, Japan.
RP Yamada, Y (reprint author), Natl Inst Dent & Craniofacial Res, Lab Cell & Dev Biol, NIH, 30 Convent Dr, Bethesda, MD 20814 USA.
EM yyamada@dir.nidcr.nih.gov
FU National Institute of Dental and Craniofacial Research; National
Institutes of Health; Japan Society for the Promotion of Science for
Young Scientists; [23790979]
FX This work was supported by grants from the Intramural Program of the
National Institute of Dental and Craniofacial Research and the National
Institutes of Health (Y.Y.). N.S. was supported in part by the Research
Fellowship of the Japan Society for the Promotion of Science for Young
Scientists and the Grant-in-Aid for Young Scientists 23790979. We thank
Andrew Cho and Ashok B. Kulkarni for creating the transgenic mouse
lines, Franca Cambi and Tadashi Yamamoto for providing the CG-4 cell
line, and Kenneth M. Yamada for providing the FAK constructs. We also
thank Tadahiro Numakawa, Naoki Adachi, and Makoto Horiuchi for their
help for the primary culture, Kang Feng and Reinhard Fassler for their
help during the initial stage of the work, and Hynda K. Kleinman and
Matthew P. Hoffman for their suggestions.
NR 28
TC 17
Z9 18
U1 0
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 22
PY 2012
VL 32
IS 34
BP 11586
EP 11599
DI 10.1523/JNEUROSCI.2045-11.2012
PG 14
WC Neurosciences
SC Neurosciences & Neurology
GA 997BZ
UT WOS:000308140500007
PM 22915103
ER
PT J
AU Fanous, S
Goldart, EM
Theberge, FRM
Bossert, JM
Shaham, Y
Hope, BT
AF Fanous, Sanya
Goldart, Evan M.
Theberge, Florence R. M.
Bossert, Jennifer M.
Shaham, Yavin
Hope, Bruce T.
TI Role of Orbitofrontal Cortex Neuronal Ensembles in the Expression of
Incubation of Heroin Craving
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
ID CONTEXT-INDUCED REINSTATEMENT; MEDIAL PREFRONTAL CORTEX;
GAMMA-AMINOBUTYRIC-ACID; DOPAMINE D-1-FAMILY RECEPTORS; COCAINE-SEEKING
BEHAVIOR; FOS PROTEIN EXPRESSION; NUCLEUS-ACCUMBENS CORE; TIME-DEPENDENT
CHANGES; DRUG-SEEKING; INDUCED RELAPSE
AB In humans, exposure to cues previously associated with heroin use often provokes relapse after prolonged withdrawal periods. In rats, cue-induced heroin seeking progressively increases after withdrawal (incubation of heroin craving). Here, we examined the role of orbitofrontal cortex (OFC) neuronal ensembles in the enhanced response to heroin cues after prolonged withdrawal or the expression of incubation of heroin craving. We trained rats to self-administer heroin (6 h/d for 10 d) and assessed cue-induced heroin seeking in extinction tests after 1 or 14 withdrawal days. Cue-induced heroin seeking increased from 1 to 14 d and was accompanied by increased Fos expression in similar to 12% of OFC neurons. Nonselective inactivation of OFC neurons with the GABA agonists baclofen + muscimol decreased cue-induced heroin seeking on withdrawal day 14 but not day 1. We then used the Daun02 inactivation procedure to assess a causal role of the minority of selectively activated Fos-expressing OFC neurons (that presumably form cue-encoding neuronal ensembles) in cue-induced heroin seeking after 14 withdrawal days. We trained c-fos-lacZ transgenic rats to self-administer heroin and 11 d later reexposed them to heroin-associated cues or novel cues for 15 min (induction day), followed by OFC Daun02 or vehicle injections 90 min later; we then tested the rats in extinction tests 3 d later. Daun02 selectively decreased cue-induced heroin seeking in rats previously reexposed to the heroin-associated cues on induction day but not in rats exposed previously to novel cues. Results suggest that heroin-cue-activated OFC neuronal ensembles contribute to the expression of incubation of heroin craving.
C1 [Fanous, Sanya; Goldart, Evan M.; Theberge, Florence R. M.; Bossert, Jennifer M.; Shaham, Yavin; Hope, Bruce T.] NIDA, Behav Neurosci Branch, Intramural Res Program, NIH,US Dept HHS, Baltimore, MD 21224 USA.
RP Hope, BT (reprint author), NIDA, Behav Neurosci Branch, Intramural Res Program, NIH,US Dept HHS, 251 Bayview Dr, Baltimore, MD 21224 USA.
EM bhope@intra.nida.nih.gov
RI Hope, Bruce/A-9223-2010; shaham, yavin/G-1306-2014
OI Hope, Bruce/0000-0001-5804-7061;
FU National Institutes of Health/National Institute on Drug Abuse
Intramural Research Program
FX This research was supported by the National Institutes of
Health/National Institute on Drug Abuse Intramural Research Program. We
thank Dr. Kenner Rice (National Institute on Drug Abuse/Intramural
Research Program) for synthesizing Daun02 and Dr. Geoff Schoenbaum for
helpful comments on this manuscript.
NR 72
TC 31
Z9 33
U1 1
U2 12
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 22
PY 2012
VL 32
IS 34
BP 11600
EP 11609
DI 10.1523/JNEUROSCI.1914-12.2012
PG 10
WC Neurosciences
SC Neurosciences & Neurology
GA 997BZ
UT WOS:000308140500008
PM 22915104
ER
PT J
AU Ohm, DT
Bloss, EB
Janssen, WG
Dietz, KC
Wadsworth, S
Lou, WD
Gee, NA
Lasley, BL
Rapp, PR
Morrison, JH
AF Ohm, Daniel T.
Bloss, Erik B.
Janssen, William G.
Dietz, Karen C.
Wadsworth, Shannon
Lou, Wendy
Gee, Nancy A.
Lasley, Bill L.
Rapp, Peter R.
Morrison, John H.
TI Clinically Relevant Hormone Treatments Fail to Induce Spinogenesis in
Prefrontal Cortex of Aged Female Rhesus Monkeys
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
ID SURGICALLY MENOPAUSAL WOMEN; DENDRITIC SPINE DENSITY; ESTROGEN
REPLACEMENT; COGNITIVE FUNCTION; POSTMENOPAUSAL WOMEN; PYRAMIDAL
NEURONS; WORKING-MEMORY; PROGESTERONE; THERAPY; ESTRADIOL
AB Preclinical animal models have provided strong evidence that estrogen (E) therapy (ET) enhances cognition and induces spinogenesis in neuronal circuits. However, clinical studies have been inconsistent, with some studies revealing adverse effects of ET, including an increased risk of dementia. In an effort to bridge this disconnect between the preclinical and clinical data, we have developed a nonhuman primate (NHP) model of ET combined with high-resolution dendritic spine analysis of dorsolateral prefrontal cortical (dlPFC) neurons. Previously, we reported cyclic ET in aged, ovariectomized NHPs increased spine density on dlPFC neurons. Here, we report that monkeys treated with cyclic E treatment paired with cyclic progesterone (P), continuous E combined with P (either cyclic or continuous), or unopposed continuous E failed to increase spines on dlPFC neurons. Given that the most prevalent form of ET prescribed to women is a combined and continuous E and P, these data bring into convergence the human neuropsychological findings and preclinical neurobiological evidence that standard hormone therapy in women is unlikely to yield the synaptic benefit presumed to underlie the cognitive enhancement reported in animal models.
C1 [Ohm, Daniel T.; Bloss, Erik B.; Janssen, William G.; Dietz, Karen C.; Wadsworth, Shannon; Morrison, John H.] Mt Sinai Sch Med, Fishberg Dept Neurosci, Friedman Brain Inst, Kastor Neurobiol Aging Lab, New York, NY 10029 USA.
[Morrison, John H.] Mt Sinai Sch Med, Dept Geriatr & Palliat Care, New York, NY 10029 USA.
[Morrison, John H.] Mt Sinai Sch Med, Grad Sch Biol Sci, New York, NY 10029 USA.
[Lou, Wendy] Univ Toronto, Dalla Lana Sch Publ Hlth, Toronto, ON M5T 3M7, Canada.
[Gee, Nancy A.; Lasley, Bill L.] Univ Calif Davis, Ctr Hlth & Environm, Davis, CA 95616 USA.
[Gee, Nancy A.; Lasley, Bill L.] Univ Calif Davis, Calif Natl Primate Res Ctr, Davis, CA 95616 USA.
[Rapp, Peter R.] NIA, Lab Expt Gerontol, Baltimore, MD 21224 USA.
RP Morrison, JH (reprint author), Mt Sinai Sch Med, Fishberg Dept Neurosci, Friedman Brain Inst, Kastor Neurobiol Aging Lab, Box 1065,1 Gustave L Levy Pl, New York, NY 10029 USA.
EM john.morrison@mssm.edu
FU NIA [AG034794, AG016765, AG006647, AG010606]; NIA Intramural Research
Program
FX This work was supported by NIA Grant AG034794 (to E. B. B.); NIA Grants
AG016765, AG006647, and AG010606 (to J.H.M.); and the NIA Intramural
Research Program (to P. R. R.). We thank Drs. Mark Baxter, Patrick Hof,
Dani Dumitriu, Yuko Hara, Jiandong Hao, and Rishi Puri for expert advice
and assistance.
NR 34
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U1 0
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 22
PY 2012
VL 32
IS 34
BP 11700
EP 11705
DI 10.1523/JNEUROSCI.1881-12.2012
PG 6
WC Neurosciences
SC Neurosciences & Neurology
GA 997BZ
UT WOS:000308140500016
PM 22915112
ER
PT J
AU Wu, T
Wang, J
Wang, CD
Hallett, M
Zang, YF
Wu, XL
Chan, P
AF Wu, Tao
Wang, Jue
Wang, Chaodong
Hallett, Mark
Zang, Yufeng
Wu, Xiaoli
Chan, Piu
TI Basal ganglia circuits changes in Parkinson's disease patients
SO NEUROSCIENCE LETTERS
LA English
DT Article
DE Parkinson's disease; Basal ganglia circuits; Dopaminergic deficits;
Granger causality analysis; Substantia nigra
ID SUBSTANTIA-NIGRA; DEFAULT MODE; CONNECTIVITY; CEREBELLUM
AB Functional changes in basal ganglia circuitry are responsible for the major clinical features of Parkinson's disease (PD). Current models of basal ganglia circuitry can only partially explain the cardinal symptoms in PD. We used functional MRI to investigate the causal connectivity of basal ganglia networks from the substantia nigra pars compacta (SNc) in PD in the movement and resting state. In controls, SNc activity predicted increased activity in the supplementary motor area, the default mode network, and dorsolateral prefrontal cortex, but, in patients, activity predicted decreases in the same structures. The SNc had decreased connectivity with the striatum, globus pallidus, subthalamic nucleus, thalamus, supplementary motor area, dorsolateral prefrontal cortex, insula, default mode network, temporal lobe, cerebellum, and pons in patients compared to controls. Levodopa administration partially normalized the pattern of connectivity. Our findings show how the dopaminergic system exerts influences on widespread brain networks, including motor and cognitive networks. The pattern of basal ganglia network connectivity is abnormal in PD secondary to dopamine depletion, and is more deviant in more severe disease. Use of functional MRI with network analysis appears to be a useful method to demonstrate basal ganglia pathways in vivo in human subjects. (C) 2012 Elsevier Ireland Ltd. All rights reserved.
C1 [Wu, Tao; Wang, Chaodong; Wu, Xiaoli; Chan, Piu] Capital Med Univ, Xuanwu Hosp, Beijing Inst Geriatr, Minist Educ,Dept Neurobiol,Key Lab Neurodegenerat, Beijing 100053, Peoples R China.
[Wang, Jue; Zang, Yufeng] Hangzhou Normal Univ, Affiliated Hosp, Ctr Cognit & Brain Disorders, Hangzhou, Zhejiang, Peoples R China.
[Hallett, Mark] NINDS, Human Motor Control Sect, Med Neurol Branch, NIH, Bethesda, MD 20892 USA.
RP Wu, T (reprint author), Capital Med Univ, Xuanwu Hosp, Beijing Inst Geriatr, Minist Educ,Dept Neurobiol,Key Lab Neurodegenerat, Beijing 100053, Peoples R China.
EM wutao69@gmail.com
RI ZANG, Yu-Feng/J-1558-2012
OI ZANG, Yu-Feng/0000-0003-1833-8010
FU National Science Foundation of China [30870693, 81071012]
FX This work was supported by grants from the National Science Foundation
of China (grant numbers 30870693 and 81071012).
NR 26
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U1 4
U2 39
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0304-3940
J9 NEUROSCI LETT
JI Neurosci. Lett.
PD AUG 22
PY 2012
VL 524
IS 1
BP 55
EP 59
DI 10.1016/j.neulet.2012.07.012
PG 5
WC Neurosciences
SC Neurosciences & Neurology
GA 000LA
UT WOS:000308386600012
PM 22813979
ER
PT J
AU Snitkin, ES
Zelazny, AM
Thomas, PJ
Stock, F
Henderson, DK
Palmore, TN
Segre, JA
AF Snitkin, Evan S.
Zelazny, Adrian M.
Thomas, Pamela J.
Stock, Frida
Henderson, David K.
Palmore, Tara N.
Segre, Julia A.
CA NISC Comparative Sequencing
TI Tracking a Hospital Outbreak of Carbapenem-Resistant Klebsiella
pneumoniae with Whole-Genome Sequencing
SO SCIENCE TRANSLATIONAL MEDICINE
LA English
DT Article
ID INTENSIVE-CARE-UNIT; ACINETOBACTER-BAUMANNII; EPIDEMIOLOGY; INFECTIONS;
STRAIN; ENTEROBACTERIACEAE; TRANSMISSION; SPREAD; COLONIZATION;
EVOLUTION
AB The Gram-negative bacteria Klebsiella pneumoniae is a major cause of nosocomial infections, primarily among immunocompromised patients. The emergence of strains resistant to carbapenems has left few treatment options, making infection containment critical. In 2011, the U. S. National Institutes of Health Clinical Center experienced an outbreak of carbapenem-resistant K. pneumoniae that affected 18 patients, 11 of whom died. Whole-genome sequencing was performed on K. pneumoniae isolates to gain insight into why the outbreak progressed despite early implementation of infection control procedures. Integrated genomic and epidemiological analysis traced the outbreak to three independent transmissions from a single patient who was discharged 3 weeks before the next case became clinically apparent. Additional genomic comparisons provided evidence for unexpected transmission routes, with subsequent mining of epidemiological data pointing to possible explanations for these transmissions. Our analysis demonstrates that integration of genomic and epidemiological data can yield actionable insights and facilitate the control of nosocomial transmission.
C1 [Zelazny, Adrian M.; Stock, Frida; Henderson, David K.; Palmore, Tara N.] NIH, Ctr Clin, Bethesda, MD 20892 USA.
[Snitkin, Evan S.; Thomas, Pamela J.; Segre, Julia A.] NHGRI, Bethesda, MD 20892 USA.
[NISC Comparative Sequencing] NIH, Intramural Sequencing Ctr NISC, Bethesda, MD 20892 USA.
RP Palmore, TN (reprint author), NIH, Ctr Clin, Bethesda, MD 20892 USA.
EM tpalmore@mail.nih.gov; jsegre@nhgri.nih.gov
FU National Human Genome Research Institute; NIH; Pharmacology Research
Associate Training Fellowship, National Institute of General Medical
Sciences
FX Funding: Supported by the National Human Genome Research Institute and
NIH Clinical Center Intramural Research Programs and by an NIH
Director's Challenge Award for genome sequencing. E. S. S. is supported
by a Pharmacology Research Associate Training Fellowship, National
Institute of General Medical Sciences.
NR 46
TC 250
Z9 253
U1 9
U2 51
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 1946-6234
J9 SCI TRANSL MED
JI Sci. Transl. Med.
PD AUG 22
PY 2012
VL 4
IS 148
AR 148ra116
DI 10.1126/scitranslmed.3004129
PG 9
WC Cell Biology; Medicine, Research & Experimental
SC Cell Biology; Research & Experimental Medicine
GA 997GB
UT WOS:000308151500006
PM 22914622
ER
PT J
AU Yeboah, J
McClelland, RL
Polonsky, TS
Burke, GL
Sibley, CT
O'Leary, D
Carr, JJ
Goff, DC
Greenland, P
Herrington, DM
AF Yeboah, Joseph
McClelland, Robyn L.
Polonsky, Tamar S.
Burke, Gregory L.
Sibley, Christopher T.
O'Leary, Daniel
Carr, Jeffery J.
Goff, David C., Jr.
Greenland, Philip
Herrington, David M.
TI Comparison of Novel Risk Markers for Improvement in Cardiovascular Risk
Assessment in Intermediate-Risk Individuals
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Article
ID CORONARY-HEART-DISEASE; INTIMA-MEDIA THICKNESS; ANKLE-BRACHIAL INDEX;
C-REACTIVE PROTEIN; ATHEROSCLEROSIS; PREDICTION; ADULTS; SCORE; EVENTS;
CLASSIFICATION
AB Context Risk markers including coronary artery calcium, carotid intima-media thickness, ankle-brachial index, brachial flow-mediated dilation, high-sensitivity C-reactive protein (CRP), and family history of coronary heart disease (CHD) have been reported to improve on the Framingham Risk Score (FRS) for prediction of CHD, but there are no direct comparisons of these markers for risk prediction in a single cohort.
Objective We compared improvement in prediction of incident CHD/cardiovascular disease (CVD) of these 6 risk markers within intermediate-risk participants (FRS >5%-<20%) in the Multi-Ethnic Study of Atherosclerosis (MESA).
Design, Setting, and Participants Of 6814 MESA participants from 6 US field centers, 1330 were intermediate risk, without diabetes mellitus, and had complete data on all 6 markers. Recruitment spanned July 2000 to September 2002, with follow-up through May 2011. Probability-weighted Cox proportional hazard models were used to estimate hazard ratios (HRs). Area under the receiver operator characteristic curve (AUC) and net reclassification improvement were used to compare incremental contributions of each marker when added to the FRS, plus race/ethnicity.
Main Outcome Measures Incident CHD defined as myocardial infarction, angina followed by revascularization, resuscitated cardiac arrest, or CHD death. Incident CVD additionally included stroke or CVD death.
Results After 7.6-year median follow-up (IQR, 7.3-7.8), 94 CHD and 123 CVD events occurred. Coronary artery calcium, ankle-brachial index, high-sensitivity CRP, and family history were independently associated with incident CHD in multivariable analyses (HR, 2.60 [95% CI, 1.94-3.50]; HR, 0.79 [95% CI, 0.66-0.95]; HR, 1.28 [95% CI, 1.00-1.64]; and HR, 2.18 [95% CI, 1.38-3.42], respectively). Carotid intima-media thickness and brachial flow-mediated dilation were not associated with incident CHD in multivariable analyses (HR, 1.17 [95% CI, 0.95-1.45] and HR, 0.95 [95% CI, 0.78-1.14]). Although addition of the markers individually to the FRS plus race/ethnicity improved AUC, coronary artery calcium afforded the highest increment (0.623 vs 0.784), while brachial flow-mediated dilation had the least (0.623 vs 0.639). For incident CHD, the net reclassification improvement with coronary artery calcium was 0.659, brachial flow-mediated dilation was 0.024, ankle-brachial index was 0.036, carotid intima-media thickness was 0.102, family history was 0.160 and high-sensitivity CRP was 0.079. Similar results were obtained for incident CVD.
Conclusions Coronary artery calcium, ankle-brachial index, high-sensitivity CRP, and family history were independent predictors of incident CHD/CVD in intermediate-risk individuals. Coronary artery calcium provided superior discrimination and risk reclassification compared with other risk markers. JAMA. 2012;308(8):788-795 www.jama.com
C1 [Yeboah, Joseph] Wake Forest Univ, Wake Forest Baptist Hlth, Dept Internal Med Cardiol, Sch Med, Winston Salem, NC 27157 USA.
[Carr, Jeffery J.] Wake Forest Univ, Sch Med, Dept Radiol, Winston Salem, NC 27157 USA.
[Burke, Gregory L.; Carr, Jeffery J.] Wake Forest Univ, Sch Med, Div Publ Hlth Sci, Winston Salem, NC 27157 USA.
[McClelland, Robyn L.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
[Polonsky, Tamar S.] Univ Chicago, Cardiol Sect, Dept Internal Med, Chicago, IL 60637 USA.
[Sibley, Christopher T.] NIH, Bethesda, MD 20892 USA.
[O'Leary, Daniel] Tufts Med Ctr, Brookline, MA USA.
[Goff, David C., Jr.] Univ Colorado, Sch Publ Hlth, Aurora, CO USA.
[Greenland, Philip] Northwestern Univ, Dept Prevent Med, Feinberg Sch Med, Chicago, IL 60611 USA.
RP Yeboah, J (reprint author), Wake Forest Univ, Wake Forest Baptist Hlth, Dept Internal Med Cardiol, Sch Med, Med Ctr Blvd, Winston Salem, NC 27157 USA.
EM jyeboah@wakehealth.edu
RI Sibley, Christopher/C-9900-2013; Carr, John/A-1938-2012
OI Carr, John/0000-0002-4398-8237
FU National Institutes of Health (NIH); National Heart, Lung, and Blood
Institute (NHLBI); NIH/NHLBI; Merck Co; NIH; [N01-HC-95159];
[N01-HC-95160]; [N01-HC-95161]; [N01-HC-95162]; [N01-HC-95163];
[N01-HC-95164]; [N01-HC-95165]; [N01-HC-95166]; [N01-HC-95167];
[R01HL098445]
FX Dr McClelland reports receipt of an institutional grant or pending grant
from the National Institutes of Health (NIH) for contracts that fund the
Multi-Ethnic Study of Atherosclerosis (MESA) study. Dr Burke reports
receipt of an institutional grant from the National Heart, Lung, and
Blood Institute (NHLBI). Dr O'Leary reports receipt of an institutional
grant and support (to the institution) for travel to meetings for the
study or other purposes from NIH. Dr Carr reports receiptof an
institutional grant from NIH/NHLBI and receipt of consultancy fees from
Merck & Co. Dr Goff reports receipt of an institutional grant and
support (to the institution) for travel to meetings for the study or
other purposes from NHLBI, board membership on the data and safety
monitoring committee for a clinical trial from Takeda, and receipt of
consultancy (operations committee member for a clinical trial) fees from
Merck & Co. Dr Greenland reports receipt of an institutional grant and
support (to the institution) for travel to meetings for the study or
other purposes) from NHLBI, receipt of a grant or pending grant from
NIH, and payment for lectures including service on speakers bureaus from
univeristies and NIH, Dr Herrington reports receipt of an institutional
grant from NIH. Drs Yeboah, Polonsky, and Sibley report no disclosures.
All authors have completed and submitted the ICMJE Form for Disclosure
of Potential Conflicts of Interest.; This research was supported by
contracts N01-HC-95159. 60, 61, 62, 63, 64, 65, 66, and N01-HC-95167 and
Diversity Supplement R01HL098445 (primary investigator, Dr Carr). A full
list of participating MESA investigators and institutions can be found
at http://www.mesa-nhlbi.org.
NR 27
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U1 4
U2 34
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 0098-7484
EI 1538-3598
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD AUG 22
PY 2012
VL 308
IS 8
BP 788
EP 795
DI 10.1001/jama.2012.9624
PG 8
WC Medicine, General & Internal
SC General & Internal Medicine
GA 991ML
UT WOS:000307705300022
PM 22910756
ER
PT J
AU Dent, AE
Moormann, AM
Yohn, CT
Kimmel, RJ
Sumba, PO
Vulule, J
Long, CA
Narum, DL
Crabb, BS
Kazura, JW
Tisch, DJ
AF Dent, Arlene E.
Moormann, Ann M.
Yohn, Christopher T.
Kimmel, Rhonda J.
Sumba, Peter O.
Vulule, John
Long, Carole A.
Narum, David L.
Crabb, Brendan S.
Kazura, James W.
Tisch, Daniel J.
TI Broadly reactive antibodies specific for Plasmodium falciparum MSP-1(19)
are associated with the protection of naturally exposed children against
infection
SO MALARIA JOURNAL
LA English
DT Article
DE Plasmodium falciparum; Antibodies; Merozoite surface protein; Malaria
infection; Children
ID MEROZOITE SURFACE PROTEIN-1; INVASION-INHIBITORY ANTIBODIES; MALARIA
VACCINE ANTIGEN; PAPUA-NEW-GUINEA; ARTEMETHER-LUMEFANTRINE; TERMINAL
FRAGMENT; GHANAIAN CHILDREN; SERUM ANTIBODIES; HOLOENDEMIC AREA;
CLINICAL MALARIA
AB Background: The 19 kDa C-terminal region of Plasmodium falciparum Merozoite Surface Protein-1 is a known target of naturally acquired humoral immunity and a malaria vaccine candidate. MSP-1(19) has four predominant haplotypes resulting in amino acid changes labelled EKNG, QKNG, QTSR and ETSR. IgG antibodies directed against all four variants have been detected, but it is not known if these variant specific antibodies are associated with haplotype-specific protection from infection.
Methods: Blood samples from 201 healthy Kenyan adults and children who participated in a 12-week treatment time-to-infection study were evaluated. Venous blood drawn at baseline (week 0) was examined for functional and serologic antibodies to MSP-1(19) and MSP-1(42) variants. MSP-1(19) haplotypes were detected by a multiplex PCR assay at baseline and weekly throughout the study. Generalized linear models controlling for age, baseline MSP-1(19) haplotype and parasite density were used to determine the relationship between infecting P. falciparum MSP-1(19) haplotype and variant-specific antibodies.
Results: A total of 964 infections resulting in 1,533 MSP-1(19) haplotypes detected were examined. The most common haplotypes were EKNG and QKNG, followed by ETSR and QTSR. Children had higher parasite densities, greater complexity of infection (>1 haplotype), and more frequent changes in haplotypes over time compared to adults. Infecting MSP-1(19) haplotype at baseline (week 0) had no influence on haplotypes detected over the subsequent 11 weeks among children or adults. Children but not adults with MSP-1(19) and some MSP-1(42) variant antibodies detected by serology at baseline had delayed time-to-infection. There was no significant association of variant-specific serology or functional antibodies at baseline with infecting haplotype at baseline or during 11 weeks of follow up among children or adults.
Conclusions: Variant transcending IgG antibodies to MSP-1(19) are associated with protection from infection in children, but not adults. These data suggest that inclusion of more than one MSP-1(19) variant may not be required in a malaria blood stage vaccine.
C1 [Dent, Arlene E.; Yohn, Christopher T.; Kimmel, Rhonda J.; Kazura, James W.; Tisch, Daniel J.] Case Western Reserve Univ, Ctr Global Hlth & Dis, Cleveland, OH 44106 USA.
[Dent, Arlene E.] Rainbow Babies & Childrens Hosp, Dept Pediat, Cleveland, OH 44106 USA.
[Moormann, Ann M.] Univ Massachusetts, Sch Med, Dept Pediat, Worcester, MA USA.
[Sumba, Peter O.; Vulule, John] Kenya Govt Med Res Ctr, Kisumu, Kenya.
[Long, Carole A.] NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA.
[Narum, David L.] NIAID, Malaria Vaccine Dev Branch, NIH, Bethesda, MD 20892 USA.
[Crabb, Brendan S.] Burnet Inst Med Res, Melbourne, Vic, Australia.
[Tisch, Daniel J.] Case Western Reserve Univ, Dept Epidemiol & Biostat, Cleveland, OH 44106 USA.
RP Dent, AE (reprint author), Case Western Reserve Univ, Ctr Global Hlth & Dis, Cleveland, OH 44106 USA.
EM arlene.dent@case.edu
RI Crabb, Brendan/F-5287-2013
FU NIH [A143906]; Intramural Program of the National Institute of Allergy
and Infectious Diseases/NIH; BWF CAMS [1006818]; Fogarty [TW006576]
FX We are grateful to the study participants for their contribution. This
work was supported by NIH A143906 (JWK). CAL and DLN are supported by
the Intramural Program of the National Institute of Allergy and
Infectious Diseases/NIH. AED is supported by BWF CAMS 1006818. POS is
supported by Fogarty grant TW006576. This work was performed with the
permission of the Director of the Kenya Medical Research Institute.
NR 45
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U1 0
U2 7
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 21
PY 2012
VL 11
AR 287
DI 10.1186/1475-2875-11-287
PG 15
WC Infectious Diseases; Parasitology; Tropical Medicine
SC Infectious Diseases; Parasitology; Tropical Medicine
GA 046GE
UT WOS:000311752700001
PM 22909378
ER
PT J
AU Uccellini, L
De Giorgi, V
Zhao, YD
Tumaini, B
Erdenebileg, N
Dudley, ME
Tomei, S
Bedognetti, D
Ascierto, ML
Liu, QZ
Simon, R
Kottyan, L
Kaufman, KM
Harley, JB
Wang, E
Rosenberg, SA
Marincola, FM
AF Uccellini, Lorenzo
De Giorgi, Valeria
Zhao, Yingdong
Tumaini, Barbara
Erdenebileg, Narnygerel
Dudley, Mark E.
Tomei, Sara
Bedognetti, Davide
Ascierto, Maria Libera
Liu, Qiuzhen
Simon, Richard
Kottyan, Leah
Kaufman, Kenneth M.
Harley, John B.
Wang, Ena
Rosenberg, Steven A.
Marincola, Francesco M.
TI IRF5 gene polymorphisms in melanoma
SO JOURNAL OF TRANSLATIONAL MEDICINE
LA English
DT Article
ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; INTERFERON REGULATORY FACTOR; METASTATIC
MELANOMA; IMMUNOLOGICAL CONSTANT; MULTIPLE-SCLEROSIS; CELL-LINES; RISK;
INTERFERON-REGULATORY-FACTOR-5; VARIANTS; THERAPY
AB Background: Interferon regulatory factor (IRF)-5 is a transcription factor involved in type I interferon signaling whose germ line variants have been associated with autoimmune pathogenesis. Since relationships have been observed between development of autoimmunity and responsiveness of melanoma to several types of immunotherapy, we tested whether polymorphisms of IRF5 are associated with responsiveness of melanoma to adoptive therapy with tumor infiltrating lymphocytes (TILs).
Methods: 140 TILs were genotyped for four single nucleotide polymorphisms (rs10954213, rs11770589, rs6953165, rs2004640) and one insertion-deletion in the IRF5 gene by sequencing. Gene-expression profile of the TILs, 112 parental melanoma metastases (MM) and 9 cell lines derived from some metastases were assessed by Affymetrix Human Gene ST 1.0 array.
Results: Lack of A allele in rs10954213 (G > A) was associated with non-response (p < 0.005). Other polymorphisms in strong linkage disequilibrium with rs10954213 demonstrated similar trends. Genes differentially expressed in vitro between cell lines carrying or not the A allele could be applied to the transcriptional profile of 112 melanoma metastases to predict their responsiveness to therapy, suggesting that IRF5 genotype may influence immune responsiveness by affecting the intrinsic biology of melanoma.
Conclusions: This study is the first to analyze associations between melanoma immune responsiveness and IRF5 polymorphism. The results support a common genetic basis which may underline the development of autoimmunity and melanoma immune responsiveness.
C1 [Uccellini, Lorenzo; De Giorgi, Valeria; Erdenebileg, Narnygerel; Tomei, Sara; Bedognetti, Davide; Ascierto, Maria Libera; Liu, Qiuzhen; Wang, Ena; Rosenberg, Steven A.] NIH, IDIS, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA.
[Uccellini, Lorenzo; De Giorgi, Valeria; Erdenebileg, Narnygerel; Tomei, Sara; Bedognetti, Davide; Ascierto, Maria Libera; Liu, Qiuzhen; Wang, Ena; Rosenberg, Steven A.] NIH, Trans NIH Ctr Human Immunol, Bethesda, MD 20892 USA.
[Uccellini, Lorenzo] Univ Milan, Inst Infect Dis, L Sacco Hosp, Milan, Italy.
[Uccellini, Lorenzo] Univ Milan, Inst Trop Dis, L Sacco Hosp, Milan, Italy.
[Zhao, Yingdong] NCI, Biometr Res Branch, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA.
[Tumaini, Barbara] NIH, Cell Proc Sect, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA.
[Bedognetti, Davide; Ascierto, Maria Libera] Univ Genoa, Dept Internal Med DiMI, I-16132 Genoa, Italy.
[Dudley, Mark E.; Kottyan, Leah; Kaufman, Kenneth M.; Harley, John B.] Cincinnati Childrens Hosp Med Ctr, Ctr Autoimmune Genom & Etiol CAGE, Cincinnati, OH 45229 USA.
[Kaufman, Kenneth M.; Harley, John B.] US Dept Vet Affairs, Med Ctr, Cincinnati, OH 45229 USA.
[Marincola, Francesco M.] NCI, Surg Branch, NIH, Bethesda, MD 20892 USA.
RP Uccellini, L (reprint author), NIH, IDIS, Dept Transfus Med, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA.
EM uccellinilorenzo@gmail.com; fmarincola@mail.cc.nih.gov
RI De Giorgi, Valeria/D-4582-2017;
OI Bedognetti, Davide/0000-0002-5857-773X; Kottyan,
Leah/0000-0003-3979-2220
FU Conquer Cancer Foundation of the American Society of Clinical Oncology
FX DB's fellowship was supported by the Conquer Cancer Foundation of the
American Society of Clinical Oncology.
NR 33
TC 17
Z9 17
U1 0
U2 4
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1479-5876
J9 J TRANSL MED
JI J. Transl. Med.
PD AUG 21
PY 2012
VL 10
AR 170
DI 10.1186/1479-5876-10-170
PG 8
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 033LJ
UT WOS:000310797500001
PM 22909381
ER
PT J
AU Raji, OY
Duffy, SW
Agbaje, OF
Baker, SG
Christiani, DC
Cassidy, A
Field, JK
AF Raji, Olaide Y.
Duffy, Stephen W.
Agbaje, Olorunshola F.
Baker, Stuart G.
Christiani, David C.
Cassidy, Adrian
Field, John K.
TI Predictive Accuracy of the Liverpool Lung Project Risk Model for
Stratifying Patients for Computed Tomography Screening for Lung Cancer A
Case-Control and Cohort Validation Study
SO ANNALS OF INTERNAL MEDICINE
LA English
DT Article
ID DECISION CURVE ANALYSIS; BREAST-CANCER; PROGNOSTIC MODELS;
CLINICAL-PRACTICE; INDIVIDUAL RISK; IMPACT; MULTICENTER; PREVENTION;
WORKSHOP; DISEASE
AB Background: External validation of existing lung cancer risk prediction models is limited. Using such models in clinical practice to guide the referral of patients for computed tomography (CT) screening for lung cancer depends on external validation and evidence of predicted clinical benefit.
Objective: To evaluate the discrimination of the Liverpool Lung Project (LLP) risk model and demonstrate its predicted benefit for stratifying patients for CT screening by using data from 3 independent studies from Europe and North America.
Design: Case-control and prospective cohort study.
Setting: Europe and North America.
Patients: Participants in the European Early Lung Cancer (EUELC) and Harvard case-control studies and the LLP population-based prospective cohort (LLPC) study.
Measurements: 5-year absolute risks for lung cancer predicted by the LLP model.
Results: The LLP risk model had good discrimination in both the Harvard (area under the receiver-operating characteristic curve [AUC], 0.76 [95% CI, 0.75 to 0.78]) and the LLPC (AUC, 0.82 [CI, 0.80 to 0.85]) studies and modest discrimination in the EUELC (AUC, 0.67 [CI, 0.64 to 0.69]) study. The decision utility analysis, which incorporates the harms and benefit of using a risk model to make clinical decisions, indicates that the LLP risk model performed better than smoking duration or family history alone in stratifying high-risk patients for lung cancer CT screening.
Limitations: The model cannot assess whether including other risk factors, such as lung function or genetic markers, would improve accuracy. Lack of information on asbestos exposure in the LLPC limited the ability to validate the complete LLP risk model.
Conclusion: Validation of the LLP risk model in 3 independent external data sets demonstrated good discrimination and evidence of predicted benefits for stratifying patients for lung cancer CT screening. Further studies are needed to prospectively evaluate model performance and evaluate the optimal population risk thresholds for initiating lung cancer screening.
C1 [Field, John K.] Univ Liverpool, Inst Translat Med, Roy Castle Lung Canc Res Programme, Canc Res Ctr, Liverpool L3 9TA, Merseyside, England.
Queen Mary Univ London, Wolfson Inst Prevent Med, Barts & London Sch Med & Dent, Kings Coll London, London, England.
Guys Hosp, London SE1 9RT, England.
NCI, Bethesda, MD 20892 USA.
Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
RP Field, JK (reprint author), Univ Liverpool, Inst Translat Med, Roy Castle Lung Canc Res Programme, Canc Res Ctr, Liverpool L3 9TA, Merseyside, England.
EM J.K.Field@liv.ac.uk
OI Field, John/0000-0003-3951-6365
FU Roy Castle Lung Cancer Foundation; National Institute for Health;
American Cancer Society; National Cancer Institute, National Institutes
of Health [CA74386, CA092824, CA090578]
FX By the Roy Castle Lung Cancer Foundation, the National Institute for
Health Research Health Technology Assessment program, and the American
Cancer Society, as well as grants CA74386, CA092824, and CA090578 from
the National Cancer Institute, National Institutes of Health (Dr.
Christiani).
NR 43
TC 63
Z9 65
U1 1
U2 11
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 21
PY 2012
VL 157
IS 4
BP 242
EP +
DI 10.7326/0003-4819-157-4-201208210-00004
PG 12
WC Medicine, General & Internal
SC General & Internal Medicine
GA 992XG
UT WOS:000307813200015
PM 22910935
ER
PT J
AU Smyth, JT
Beg, AM
Wu, SL
Putney, JW
Rusan, NM
AF Smyth, Jeremy T.
Beg, Amber M.
Wu, Shilan
Putney, James W., Jr.
Rusan, Nasser M.
TI Phosphoregulation of STIM1 Leads to Exclusion of the Endoplasmic
Reticulum from the Mitotic Spindle
SO CURRENT BIOLOGY
LA English
DT Article
ID OPERATED CALCIUM-ENTRY; END-TRACKING PROTEINS; MAMMALIAN-CELLS;
PHOSPHORYLATION; GOLGI; DYNAMICS; BINDING; ER; APPARATUS; MEMBRANE
AB The endoplasmic reticulum (ER) undergoes significant reorganization between interphase and mitosis, but the underlying mechanisms are unknown [1]. Stromal interaction molecule 1 (STIM1) is an ER Ca2+ sensor that activates store-operated Ca2+ entry (SOCE) [2, 3] and also functions in ER morphogenesis through its interaction with the microtubule +TIP protein end binding 1 (EB1) [4]. We previously demonstrated that phosphorylation of STIM1 during mitosis suppresses SOCE [5]. We now show that STIM1 phosphorylation is a major regulatory mechanism that excludes ER from the mitotic spindle. In mitotic He La cells, the ER forms concentric sheets largely excluded from the mitotic spindle. We show that STIM1 dissociates from EB1 in mitosis and localizes to the concentric ER sheets. However, a nonphosphorylatable STIM1 mutant (STIM1(10A)) colocalized extensively with EB1 and drove ER mislocalization by pulling ER tubules into the spindle. This effect was rescued by mutating the EB1 interaction site of STIM1(10A), demonstrating that aberrant association of STIM1(10A) with EB1 is responsible for the ER mislocalization. A STIM1 phosphomimetic exhibited significantly impaired +TIP tracking in interphase but was ineffective at inhibiting SOCE, suggesting different mechanisms of regulation of these two STIM1 functions by phosphorylation. Thus, ER spindle exclusion and ER-dependent Ca2+ signaling during mitosis require multi-modal STIM1 regulation by phosphorylation.
C1 [Wu, Shilan; Putney, James W., Jr.] NIEHS, Lab Signal Transduct, NIH, Res Triangle Pk, NC 27709 USA.
[Smyth, Jeremy T.; Beg, Amber M.; Rusan, Nasser M.] NHLBI, Cell Biol & Physiol Ctr, NIH, Bethesda, MD 20892 USA.
RP Putney, JW (reprint author), NIEHS, Lab Signal Transduct, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.
EM putney@niehs.nih.gov; nasser@nih.gov
RI Rusan, Nasser/P-3511-2016
FU NIH, National Heart, Lung and Blood Institute; National Institute of
Environmental Health Sciences
FX This research was supported by the Intramural Research Program of the
NIH, National Heart, Lung and Blood Institute, and National Institute of
Environmental Health Sciences. We acknowledge Christian Combs in the
NHLBI Light Microscopy Core Facility, Jeff Tucker and Agnes Janoshazi in
the NIEHS Confocal Core Facility, and Leigh Samsel and Pradeep Dagur in
the NHLBI Flow Cytometry Core Facility for assistance with experiments.
We also thank Brian Galletta, Dorothy Lent, Stephen Shears, and Carmen
Williams for helpful comments on the manuscript.
NR 25
TC 36
Z9 37
U1 0
U2 2
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0960-9822
J9 CURR BIOL
JI Curr. Biol.
PD AUG 21
PY 2012
VL 22
IS 16
BP 1487
EP 1493
DI 10.1016/j.cub.2012.05.057
PG 7
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 992QO
UT WOS:000307795000021
PM 22748319
ER
PT J
AU Haspel, G
Schwartz, A
Streets, A
Camacho, DE
Soares, D
AF Haspel, Gal
Schwartz, Adina
Streets, Amy
Escobar Camacho, Daniel
Soares, Daphne
TI By the teeth of their skin, cavefish find their way
SO CURRENT BIOLOGY
LA English
DT Letter
ID LATERAL-LINE; ASTYANAX-FASCIATUS; FISH
C1 [Haspel, Gal] NINDS, Neural Control Lab, Sect Dev Neurobiol, NIH, Bethesda, MD 20892 USA.
[Schwartz, Adina; Streets, Amy; Soares, Daphne] Univ Maryland, Coll Comp Math & Nat Sci, Dept Biol, College Pk, MD 20742 USA.
[Escobar Camacho, Daniel] Pontificia Univ Catolica Ecuador, Fac Ciencias Exactas & Nat, EC-170109 Quito, Pichincha, Ecuador.
RP Haspel, G (reprint author), NINDS, Neural Control Lab, Sect Dev Neurobiol, NIH, Bethesda, MD 20892 USA.
EM daph@umd.edu
OI Haspel, Gal/0000-0001-6701-697X
FU Intramural NIH HHS [Z99 NS999999]
NR 10
TC 4
Z9 4
U1 0
U2 16
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0960-9822
J9 CURR BIOL
JI Curr. Biol.
PD AUG 21
PY 2012
VL 22
IS 16
BP R629
EP R630
DI 10.1016/j.cub.2012.06.035
PG 2
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 992QO
UT WOS:000307795000006
PM 22917507
ER
PT J
AU Hassan, SA
AF Hassan, Sergio A.
TI Self-consistent treatment of the local dielectric permittivity and
electrostatic potential in solution for polarizable macromolecular force
fields
SO JOURNAL OF CHEMICAL PHYSICS
LA English
DT Article
ID POISSON-BOLTZMANN EQUATION; FINITE-ELEMENT SOLUTION; LIQUID-STRUCTURE
FORCES; PROTEIN HYDRATION; POLAR LIQUIDS; AMINO-ACID; WATER; SOLVATION;
MODEL; DENSITY
AB A self-consistent method is presented for the calculation of the local dielectric permittivity and electrostatic potential generated by a solute of arbitrary shape and charge distribution in a polar and polarizable liquid. The structure and dynamics behavior of the liquid at the solute/liquid interface determine the spatial variations of the density and the dielectric response. Emphasis here is on the treatment of the interface. The method is an extension of conventional methods used in continuum protein electrostatics, and can be used to estimate changes in the static dielectric response of the liquid as it adapts to charge redistribution within the solute. This is most relevant in the context of polarizable force fields, during electron structure optimization in quantum chemical calculations, or upon charge transfer. The method is computationally efficient and well suited for code parallelization, and can be used for on-the-fly calculations of the local permittivity in dynamics simulations of systems with large and heterogeneous charge distributions, such as proteins, nucleic acids, and polyelectrolytes. Numerical calculation of the system free energy is discussed for the general case of a liquid with field-dependent dielectric response. [http://dx.doi.org/10.1063/1.4742910]
C1 NIH, Ctr Mol Modeling, DCB CIT, US DHHS, Bethesda, MD 20892 USA.
RP Hassan, SA (reprint author), NIH, Ctr Mol Modeling, DCB CIT, US DHHS, Bethesda, MD 20892 USA.
EM hassan@mail.nih.gov
FU National of Institutes of Health (NIH), Center for Information
Technology
FX This study was supported by the Intramural Research Program of the
National of Institutes of Health (NIH), Center for Information
Technology, and utilized the high-performance computational capabilities
of the Biowulf Linux cluster at the NIH, Bethesda, MD, USA.
NR 66
TC 4
Z9 4
U1 1
U2 16
PU AMER INST PHYSICS
PI MELVILLE
PA 1305 WALT WHITMAN RD, STE 300, MELVILLE, NY 11747-4501 USA
SN 0021-9606
EI 1089-7690
J9 J CHEM PHYS
JI J. Chem. Phys.
PD AUG 21
PY 2012
VL 137
IS 7
AR 074102
DI 10.1063/1.4742910
PG 9
WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical
SC Chemistry; Physics
GA 999AE
UT WOS:000308280700002
PM 22920098
ER
PT J
AU Wishart, GC
Bajdik, CD
Dicks, E
Provenzano, E
Schmidt, MK
Sherman, M
Greenberg, DC
Green, AR
Gelmon, KA
Kosma, VM
Olson, JE
Beckmann, MW
Winqvist, R
Cross, SS
Severi, G
Huntsman, D
Pylkas, K
Ellis, I
Nielsen, TO
Giles, G
Blomqvist, C
Fasching, PA
Couch, FJ
Rakha, E
Foulkes, WD
Blows, FM
Begin, LR
van't Veer, LJ
Southey, M
Nevanlinna, H
Mannermaa, A
Cox, A
Cheang, M
Baglietto, L
Caldas, C
Garcia-Closas, M
Pharoah, PDP
AF Wishart, G. C.
Bajdik, C. D.
Dicks, E.
Provenzano, E.
Schmidt, M. K.
Sherman, M.
Greenberg, D. C.
Green, A. R.
Gelmon, K. A.
Kosma, V-M
Olson, J. E.
Beckmann, M. W.
Winqvist, R.
Cross, S. S.
Severi, G.
Huntsman, D.
Pylkas, K.
Ellis, I.
Nielsen, T. O.
Giles, G.
Blomqvist, C.
Fasching, P. A.
Couch, F. J.
Rakha, E.
Foulkes, W. D.
Blows, F. M.
Begin, L. R.
van't Veer, L. J.
Southey, M.
Nevanlinna, H.
Mannermaa, A.
Cox, A.
Cheang, M.
Baglietto, L.
Caldas, C.
Garcia-Closas, M.
Pharoah, P. D. P.
TI PREDICT Plus: development and validation of a prognostic model for early
breast cancer that includes HER2
SO BRITISH JOURNAL OF CANCER
LA English
DT Article
DE breast cancer; HER2; prognostic model; HER2
ID POPULATION-BASED VALIDATION; ADJUVANT CHEMOTHERAPY; TUMOR
CHARACTERISTICS; PREMENOPAUSAL WOMEN; RANDOMIZED-TRIALS; FOLLOW-UP;
SURVIVAL; INDEX; RISK; TRASTUZUMAB
AB BACKGROUND: Predict (www.predict.nhs.uk) is an online, breast cancer prognostication and treatment benefit tool. The aim of this study was to incorporate the prognostic effect of HER2 status in a new version (Predict +), and to compare its performance with the original Predict and Adjuvantl.
METHODS: The prognostic effect of HER2 status was based on an analysis of data from 10 179 breast cancer patients from 14 studies in the Breast Cancer Association Consortium. The hazard ratio estimates were incorporated into Predict. The validation study was based on 1653 patients with early-stage invasive breast cancer identified from the British Columbia Breast Cancer Outcomes Unit. Predicted overall survival (OS) and breast cancer-specific survival (BCSS) for Predict I, Predict and Adjuvant! were compared with observed outcomes.
RESULTS: All three models performed well for both OS and BCSS. Both Predict models provided better BCSS estimates than Adjuvantl. In the subset of patients with HER2-positive tumours, Predict + performed substantially better than the other two models for both OS and BCSS.
CONCLUSION: Predict + is the first clinical breast cancer prognostication tool that includes tumour HER2 status. Use of the model might lead to more accurate absolute treatment benefit predictions for individual patients. British Journal of Cancer (2012) 107, 800-807. doi:10.1038/bjc.2012.338 www.bjcancer.com Published online 31 July 2012 (C) 2012 Cancer Research UK
C1 [Dicks, E.; Provenzano, E.; Blows, F. M.; Caldas, C.; Pharoah, P. D. P.] Univ Cambridge, Dept Oncol, Strangeways Res Lab, Cambridge CB1 8RN, England.
[Wishart, G. C.] Addenbrookes Hosp, Cambridge Breast Unit, Cambridge, England.
[Bajdik, C. D.] British Columbia Canc Agcy, Canc Control Res Program, Vancouver, BC V5Z 4E6, Canada.
[Schmidt, M. K.; van't Veer, L. J.] Netherlands Canc Inst, Div Mol Pathol, Amsterdam, Netherlands.
[Schmidt, M. K.; van't Veer, L. J.] Netherlands Canc Inst, Div Psychosocial Res & Epidemiol, Amsterdam, Netherlands.
[Sherman, M.] NCI, Div Canc Epidemiol & Genet, Rockville, MD USA.
[Greenberg, D. C.] Eastern Canc Registrat & Informat Ctr, Cambridge, England.
[Green, A. R.] Univ Nottingham, Sch Mol Med Sci, Dept Pathol, Nottingham NG7 2RD, England.
[Gelmon, K. A.] Univ British Columbia, British Columbia Canc Agcy, Dept Med Oncol, Vancouver, BC V5Z 1M9, Canada.
[Kosma, V-M; Mannermaa, A.] Univ Eastern Finland, Sch Med, Inst Clin Med Pathol & Forens Med, Kuopio, Finland.
[Kosma, V-M; Mannermaa, A.] Kuopio Univ Hosp, Dept Pathol, SF-70210 Kuopio, Finland.
[Olson, J. E.] Mayo Clin, Dept Hlth Sci Res, Rochester, MN USA.
[Beckmann, M. W.; Fasching, P. A.] Univ Erlangen Nurnberg, Univ Hosp Erlangen, Univ Breast Ctr Franconia, Dept Gynecol & Obstet, Erlangen, Germany.
[Winqvist, R.] Univ Oulu, Dept Clin Genet, Canc Genet Lab, Oulu, Finland.
[Winqvist, R.] Univ Oulu, Bioctr, Oulu, Finland.
[Winqvist, R.] Oulu Univ Hosp, Oulu, Finland.
[Cross, S. S.] Univ Sheffield, Dept Neurosci, Acad Unit Pathol, Sheffield, S Yorkshire, England.
[Severi, G.; Giles, G.; Southey, M.; Baglietto, L.] Canc Council Victoria, Canc Epidemiol Ctr, Melbourne, Vic, Australia.
[Huntsman, D.; Nielsen, T. O.; Cheang, M.] Univ British Columbia, Dept Pathol & Lab Med, Vancouver, BC V5Z 1M9, Canada.
[Pylkas, K.; Blomqvist, C.] Univ Helsinki, Dept Oncol, Helsinki, Finland.
[Pylkas, K.; Blomqvist, C.; Nevanlinna, H.] Univ Helsinki, Cent Hosp, Helsinki, Finland.
[Ellis, I.; Rakha, E.] Nottingham Univ Hosp NHS Trust, Sch Mol Med Sci, Dept Histopathol, Nottingham, England.
[Ellis, I.; Rakha, E.] Univ Nottingham, Nottingham NG7 2RD, England.
[Couch, F. J.] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA.
[Foulkes, W. D.] McGill Univ, Dept Oncol, Program Canc Genet, Montreal, PQ, Canada.
[Foulkes, W. D.] McGill Univ, Dept Human Genet, Program Canc Genet, Montreal, PQ, Canada.
[Begin, L. R.] McGill Univ, Dept Pathol, Montreal, PQ, Canada.
[Begin, L. R.] Hop Sacre, Montreal, PQ, Canada.
[Nevanlinna, H.] Univ Helsinki, Dept Obstet & Gynaecol, Helsinki, Finland.
[Cox, A.] Univ Sheffield, Inst Canc Studies, Dept Oncol, Sheffield, S Yorkshire, England.
[Garcia-Closas, M.] Inst Canc Res, Div Genet & Epidemiol, Sutton, Surrey, England.
[Garcia-Closas, M.] Inst Canc Res, Breakthrough Breast Canc Res Ctr, Sutton, Surrey, England.
RP Pharoah, PDP (reprint author), Univ Cambridge, Dept Oncol, Strangeways Res Lab, Worts Causeway, Cambridge CB1 8RN, England.
EM paul.pharoah@srl.cam.ac.uk
RI Caldas, Carlos/A-7543-2008; Garcia-Closas, Montserrat /F-3871-2015;
OI Garcia-Closas, Montserrat /0000-0003-1033-2650; Cross,
Simon/0000-0003-2044-1754; Nevanlinna, Heli/0000-0002-0916-2976;
foulkes, william/0000-0001-7427-4651; Cox, Angela/0000-0002-5138-1099;
Giles, Graham/0000-0003-4946-9099
FU Breast Cancer Campaign, Cancer Research UK [C490/A10119, C490/A10124];
US National Institutes of Health [CA122340, CA122340Z, CA116201];
special Government Funding (EVO) of Kuopio University Hospital; Cancer
Fund of North Savo; Finnish Cancer Organisation; Academy of Finland
[132473]; University of Eastern Finland; Helsinki University Central
Hospital Research Fund; Finnish Cancer Society; Sigrid Juselius
Foundation; Susan G Komen for the Cure, Yorkshire Cancer Research;
Cambridge NIHR Biomedical Research Centre; Cambridge Experimental Cancer
Medicine Centre; Michael Smith Foundation For Health Research; Dutch
Cancer Society [NKI DCS 2009-4363]
FX We thank all the patients who took part in the component BCAC studies
and the many other individuals who have made these studies possible. In
particular, we thank Hans Peterse, Rob Tollenaar, Vincent Smit, Renate
de Groot, Renate Udo, Flora van Leeuwen (ABCS); Claudia Rauh, Julia
Wessel (BBCC); the BC Cancer Registry and Breast Cancer Outcomes Unit
(BCCA); Paivi Heikkila, Kirsimari Aaltonen, Kristiina Aittomaki,Ari
Ristimaki, Laura Hautala, Mira Heinonen, RN Hanna Jantti, Irja Erkkila,
and the Finnish Cancer Registry (HEBCS); Lars A Akslen (JGH); Vicky
Cafourek, Matthew Kosel and Zachary Fredericksen (MCBCS); John Hopper,
Dallas English and Helen Kelsall (MCCS), (NOBCS); Arja Jukkola-Vuorinen,
Taina Turpeenniemi-Hujanen, Mervi Grip, Saila Kauppila, Kari Mononen and
Meeri Otsukka (OBCS); Louise Brinton, Jonine Figueroa, Kelly Bolton,
Neonila, Szeszenia-Dabrowska, Beata Peplonska, Witold Zatonski, Pei
Chao, and Michael Stagner (PBCS); Sabapathy, Balasubramanian, Malcolm WR
Reed, Helen Cramp, and Dan Connley (SBCS); Sarah-Jane Dawson and the
SEARCH team (SEARCH). The contributing studies are funded by grants from
Breast Cancer Campaign (2004Nov49), Cancer Research UK (C490/A10119,
C490/A10124); US National Institutes of Health (CA122340, CA122340Z,
CA116201); special Government Funding (EVO) of Kuopio University
Hospital; the Cancer Fund of North Savo; the Finnish Cancer
Organisation; the Academy of Finland (132473); strategic funding of the
University of Eastern Finland; the Helsinki University Central Hospital
Research Fund; the Finnish Cancer Society; the Sigrid Juselius
Foundation; Susan G Komen for the Cure, Yorkshire Cancer Research. GCW
and CC received research funding from the Cambridge NIHR Biomedical
Research Centre and the Cambridge Experimental Cancer Medicine Centre.
CDB, TN and DH are partly supported through Career Awards from the
Michael Smith Foundation For Health Research. MKS is funded by the Dutch
Cancer Society (NKI DCS 2009-4363).
NR 42
TC 32
Z9 32
U1 0
U2 5
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0007-0920
J9 BRIT J CANCER
JI Br. J. Cancer
PD AUG 21
PY 2012
VL 107
IS 5
BP 800
EP 807
DI 10.1038/bjc.2012.338
PG 8
WC Oncology
SC Oncology
GA 992JG
UT WOS:000307771100007
PM 22850554
ER
PT J
AU Nasrollahzadeh, D
Malekzadeh, R
Aghcheli, K
Sotoudeh, M
Merat, S
Islami, F
Kamangar, F
Abnet, CC
Shakeri, R
Pourshams, A
Semnani, S
Boffetta, P
Dawsey, SM
Ye, W
AF Nasrollahzadeh, D.
Malekzadeh, R.
Aghcheli, K.
Sotoudeh, M.
Merat, S.
Islami, F.
Kamangar, F.
Abnet, C. C.
Shakeri, R.
Pourshams, A.
Semnani, S.
Boffetta, P.
Dawsey, S. M.
Ye, W.
TI Gastric atrophy and oesophageal squamous cell carcinoma: possible
interaction with dental health and oral hygiene habit
SO BRITISH JOURNAL OF CANCER
LA English
DT Article
DE atrophic gastritis; oesophageal neoplasm; relative risk; dental health;
oral hygiene; pepsinogen
ID HELICOBACTER-PYLORI INFECTION; HIGH-RISK AREA; SERUM PEPSINOGENS;
GOLESTAN COHORT; TOOTH LOSS; CANCER; IRAN; STOMACH; TOBACCO
AB BACKGROUND: Gastric fundal atrophy has been hypothesised to increase the risk of oesophageal squamous cell carcinoma (OSCC), but studies have shown inconsistent results.
METHODS: We measured serum pepsinogen I (PGI) and pepsinogen II (PGII) among 293 incident cases and 524 matched neighbourhood controls in a high-risk area of Northern Iran. Conditional logistic regression model was used to estimate odds ratios (ORs) and their 95% confidence intervals (CIs).
RESULTS: After controlling for age, sex, residence area and other potential confounders, gastric atrophy (defined by a validated criterion, PGI <55 mu g dl(-1)) was associated with a two-fold increased risk (OR = 2.01, 95% CI: 1.18, 3.45) of OSCC in the absence of nonatrophic pangastritis (defined as PGII < 11.8 mu g dl(-1)). Stratification by PGII decreased the misclassification errors due to cancer-induced gastritis. Presence of both poor dental health, indicated by higher than median sum of decayed, missing, and filled teeth (DMFT score), and gastric atrophy further increased the risk of OSCC (OR = 4.15, 95% CI: 2.04, 8.42) with relative excess risk due to interaction (RERI) of 1.47 (95% CI: - 1.15, 4.1). Coexistence of poor oral hygiene habit with gastric atrophy elevated OSCC risk eight times (OR = 8.65, 95% CI: 3.65, 20.46) and the additive interaction index was marginally statistically significant (RERI = 4.34, 95% CI: - 1.07, 9.76).
CONCLUSION: Gastric atrophy is a risk factor for OSCC, and poor dental health and oral hygiene habit may act synergistically in increasing the risk. British Journal of Cancer (2012) 107, 888-894. doi: 10.1038/bjc.2012.332 www.bjcancer.com Published online 19 July 2012 (C) 2012 Cancer Research UK
C1 [Nasrollahzadeh, D.; Malekzadeh, R.; Aghcheli, K.; Sotoudeh, M.; Merat, S.; Islami, F.; Kamangar, F.; Shakeri, R.; Pourshams, A.] Univ Tehran Med Sci, Digest Dis Res Ctr, Tehran 14117, Iran.
[Nasrollahzadeh, D.; Ye, W.] Karolinska Inst, Dept Med Epidemiol & Biostat, S-17177 Stockholm, Sweden.
[Islami, F.; Boffetta, P.] Mt Sinai Sch Med, Inst Translat Epidemiol, New York, NY 10029 USA.
[Islami, F.; Boffetta, P.] Mt Sinai Sch Med, Tisch Canc Inst, New York, NY 10029 USA.
[Kamangar, F.] Morgan State Univ, Dept Publ Hlth Anal, Sch Community Hlth & Policy, Baltimore, MD 21251 USA.
[Abnet, C. C.; Dawsey, S. M.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Semnani, S.] Gorgan Univ Med Sci, Golestan Res Ctr Gastroenterol & Hepatol, Gorgan 491751141, Iran.
RP Malekzadeh, R (reprint author), Univ Tehran Med Sci, Digest Dis Res Ctr, N Karegar Ave, Tehran 14117, Iran.
EM malek@ams.ac.ir; weimin.ye@ki.se
RI Abnet, Christian/C-4111-2015; Semnani, Shahryar/N-2270-2016;
OI Abnet, Christian/0000-0002-3008-7843; Semnani,
Shahryar/0000-0002-8768-6142; , Ramin/0000-0003-0487-3629; Malekzadeh,
Reza/0000-0003-1043-3814
FU Digestive Disease Research Centre of Tehran University of Medical
Sciences [82-603]; Swedish Research Council [VR-60535801]; National
Cancer Institute at the National Institutes of Health; Martin Rinds
Foundation (Sweden); KID grant, Karolinska Institutet faculty funds for
postgraduate students
FX We thank the local health network workers (Behvarz) for their
contribution to this study. This work was supported by Digestive Disease
Research Centre of Tehran University of Medical Sciences (Grant 82-603),
Swedish Research Council (VR-60535801), intramural funds of the National
Cancer Institute at the National Institutes of Health, Martin Rinds
Foundation (Sweden), and KID grant, Karolinska Institutet faculty funds
for postgraduate students (December 2008).
NR 31
TC 8
Z9 9
U1 1
U2 6
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0007-0920
EI 1532-1827
J9 BRIT J CANCER
JI Br. J. Cancer
PD AUG 21
PY 2012
VL 107
IS 5
BP 888
EP 894
DI 10.1038/bjc.2012.332
PG 7
WC Oncology
SC Oncology
GA 992JG
UT WOS:000307771100018
PM 22814581
ER
PT J
AU Koulaouzidis, A
Karargyris, A
AF Koulaouzidis, Anastasios
Karargyris, Alexandros
TI Three-dimensional image reconstruction in capsule endoscopy
SO WORLD JOURNAL OF GASTROENTEROLOGY
LA English
DT Article
DE Capsule endoscopy; Three-dimensional; Reconstruction; Angioectasias;
Software
ID SHAPE
AB To date, limited research has been carried out in developing methods and materials that offer three-dimensional (3-D) representation of the digestive tract. In the field of capsule endoscopy (CE), hardware approaches have been developed that provide real time both 3-D information and texture using an infrared projector and a complementary metal oxide semiconductor camera. The major drawbacks of this system are its size, power consumption and packaging issues. A software approach to approximate a 3-D representation of digestive tract surface utilising current CE technology has been proposed. The algorithm utilizes the Shape from Shading technique and seem to provide promising results for polypoid structures and angioectasias. Further clinical evaluation is currently under way. (C) 2012 Baishideng. All rights reserved.
C1 [Koulaouzidis, Anastasios] Royal Infirm Edinburgh NHS Trust, Ctr Liver & Digest Disorders, Edinburgh EH16 4SA, Midlothian, Scotland.
[Karargyris, Alexandros] NIH, Natl Lib Med, Bethesda, MD 20814 USA.
RP Koulaouzidis, A (reprint author), Royal Infirm Edinburgh NHS Trust, Ctr Liver & Digest Disorders, 51 Little France Crescent, Edinburgh EH16 4SA, Midlothian, Scotland.
EM akoulaouzidis@hotmail.com
NR 17
TC 9
Z9 10
U1 1
U2 11
PU BAISHIDENG PUBLISHING GROUP INC
PI PLEASANTON
PA 8226 REGENCY DR, PLEASANTON, CA 94588 USA
SN 1007-9327
EI 2219-2840
J9 WORLD J GASTROENTERO
JI World J. Gastroenterol.
PD AUG 21
PY 2012
VL 18
IS 31
BP 4086
EP 4090
DI 10.3748/wjg.v18.i31.4086
PG 5
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 995CZ
UT WOS:000307986800003
PM 22919239
ER
PT J
AU Spehalski, E
Kovalchuk, AL
Collins, JT
Liang, GQ
Dubois, W
Morse, HC
Ferguson, DO
Casellas, R
Dunnick, WA
AF Spehalski, Elizabeth
Kovalchuk, Alexander L.
Collins, John T.
Liang, Genqing
Dubois, Wendy
Morse, Herbert. C., III
Ferguson, David O.
Casellas, Rafael
Dunnick, Wesley A.
TI Oncogenic Myc translocations are independent of chromosomal location and
orientation of the immunoglobulin heavy chain locus
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
ID INDUCED CYTIDINE DEAMINASE; CLASS-SWITCH RECOMBINATION; PLASMA-CELL
TUMORS; C-MYC; B-CELL; GENOMIC INSTABILITY; SEQUENCING REVEALS;
TRANSGENIC MICE; LYMPHOMA-CELLS; CONTROL REGION
AB Many tumors are characterized by recurrent translocations between a tissue-specific gene and a proto-oncogene. The juxtaposition of the Ig heavy chain gene and Myc in Burkitt's lymphoma and in murine plasmacytoma is a classic example. Regulatory elements within the heavy chain constant region locus are required for Myc translocation and/or deregulation. However, many genes are regulated by cis-acting elements at distances up to 1,000 kb outside the locus. Such putative distal elements have not been examined for the heavy chain locus, particularly in the context of Myc translocations. We demonstrate that a transgene containing the Ig heavy chain constant region locus, inserted into five different chromosomal locations, can undergo translocations involving Myc. Furthermore, these translocations are able to generate plasmacytomas in each transgenic line. We conclude that the heavy chain constant region locus itself includes all of the elements necessary for both the translocation and the deregulation of the proto-oncogene.
C1 [Collins, John T.; Dunnick, Wesley A.] Univ Michigan, Sch Med, Dept Microbiol & Immunol, Ann Arbor, MI 48109 USA.
[Spehalski, Elizabeth; Ferguson, David O.] Univ Michigan, Sch Med, Dept Pathol, Ann Arbor, MI 48109 USA.
[Kovalchuk, Alexander L.; Dubois, Wendy; Morse, Herbert. C., III] NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA.
[Liang, Genqing; Casellas, Rafael] NIAMSD, Immunogenet Mol Lab, Bethesda, MD 20892 USA.
[Liang, Genqing; Casellas, Rafael] NIH, Lab Canc Biol & Genet, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Dunnick, WA (reprint author), Univ Michigan, Sch Med, Dept Microbiol & Immunol, Ann Arbor, MI 48109 USA.
EM wesadunn@umich.edu
OI Morse, Herbert/0000-0002-9331-3705
FU National Institutes of Health (NIH) [AI068749, AI076057, HL079118,
T32-AI007413]; Intramural Research Program of the NIH; National
Institute of Allergy and Infectious Diseases; National Cancer Institute;
National Institute of Arthritis and Musculoskeletal and Skin Diseases
FX We thank Drs. Michael Potter, Seigfried Janz, and Konrad Huppi for
advice; Jian Shi for technical assistance; and Dr. Gary Huffnagel for
the use of his labotatory's cytospin centrifuge and reagents. This work
was supported by National Institutes of Health (NIH) Grants AI068749 and
AI076057 (to W.D.), HL079118 (to D.O.F.), and T32-AI007413 (to E.S.)
and, in part, by the Intramural Research Program of the NIH, National
Institute of Allergy and Infectious Diseases, National Cancer Institute,
and National Institute of Arthritis and Musculoskeletal and Skin
Diseases.
NR 41
TC 5
Z9 5
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 21
PY 2012
VL 109
IS 34
BP 13728
EP 13732
DI 10.1073/pnas.1202882109
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 996KJ
UT WOS:000308085200058
PM 22869734
ER
PT J
AU Liu, SH
Bachran, C
Gupta, P
Miller-Randolph, S
Wang, HL
Crown, D
Zhang, Y
Wein, AN
Singh, R
Fattah, R
Leppla, SH
AF Liu, Shihui
Bachran, Christopher
Gupta, Pradeep
Miller-Randolph, Sharmina
Wang, Hailun
Crown, Devorah
Zhang, Yi
Wein, Alexander N.
Singh, Rajat
Fattah, Rasem
Leppla, Stephen H.
TI Diphthamide modification on eukaryotic elongation factor 2 is needed to
assure fidelity of mRNA translation and mouse development
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
ID CAPILLARY MORPHOGENESIS PROTEIN-2; ADP-RIBOSYLATING TOXINS; PSEUDOMONAS
EXOTOXIN-A; DIPHTHERIA-TOXIN; SACCHAROMYCES-CEREVISIAE; ANTHRAX TOXIN;
FACTOR-II; RESISTANT MUTANTS; BIOSYNTHESIS; CELLS
AB To study the role of the diphthamide modification on eukaryotic elongation factor 2 (eEF2), we generated an eEF2 Gly(717)Arg mutant mouse, in which the first step of diphthamide biosynthesis is prevented. Interestingly, the Gly(717)-to-Arg mutation partially compensates the eEF2 functional loss resulting from diphthamide deficiency, possibly because the added + 1 charge compensates for the loss of the + 1 charge on diphthamide. Therefore, in contrast to mouse embryonic fibroblasts (MEFs) from OVCA1(-/-) mice, eEF2(G717R/G717R) MEFs retain full activity in polypeptide elongation and have normal growth rates. Furthermore, eEF2(G717R/G717R) mice showed milder phenotypes than OVCA1(-/-) mice (which are 100% embryonic lethal) and a small fraction survived to adulthood without obvious abnormalities. Moreover, eEF2(G717R/G717R/OVCA1-/-) double mutant mice displayed the milder phenotypes of the eEF2(G717R/G717R) mice, suggesting that the embryonic lethality of OVCA1(-/-) mice is due to diphthamide deficiency. We confirmed that the diphthamide modification is essential for eEF2 to prevent -1 frameshifting during translation and show that the Gly(717)-to-Arg mutation cannot rescue this defect.
C1 [Liu, Shihui; Bachran, Christopher; Gupta, Pradeep; Miller-Randolph, Sharmina; Wang, Hailun; Crown, Devorah; Zhang, Yi; Wein, Alexander N.; Singh, Rajat; Fattah, Rasem; Leppla, Stephen H.] NIAID, Microbial Pathogenesis Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Liu, SH (reprint author), NIAID, Microbial Pathogenesis Sect, Parasit Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM shliu@niaid.nih.gov; sleppla@niaid.nih.gov
OI Singh, Rajat/0000-0002-9542-1929
FU National Institute of Allergy and Infectious Diseases, National
Institutes of Health
FX We thank Dr. Richard R. Behringer for providing OVCA1-targeted mice,
Drs. Dominic Dulude and Lea Brakier-Gingras for providing pDual-HIV(-1)
plasmid, and Dr. Mahtab Moayeri for helpful discussion. This research
was supported by the intramural research program of the National
Institute of Allergy and Infectious Diseases, National Institutes of
Health.
NR 30
TC 22
Z9 22
U1 0
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 21
PY 2012
VL 109
IS 34
BP 13817
EP 13822
DI 10.1073/pnas.1206933109
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 996KJ
UT WOS:000308085200073
PM 22869748
ER
PT J
AU Giedd, JN
Raznahan, A
Mills, KL
Lenroot, RK
AF Giedd, Jay N.
Raznahan, Armin
Mills, Kathryn L.
Lenroot, Rhoshel K.
TI Review: magnetic resonance imaging of male/female differences in human
adolescent brain anatomy
SO BIOLOGY OF SEX DIFFERENCES
LA English
DT Article
ID HUMAN CORPUS-CALLOSUM; ADULT HUMAN BRAIN; WHITE-MATTER ARCHITECTURE;
NORMAL SEXUAL-DIMORPHISM; CORTICAL THICKNESS; CEREBRAL-CORTEX;
GRAY-MATTER; GENDER DIFFERENCES; MOUSE-BRAIN; AGE
AB Improvements in neuroimaging technologies, and greater access to their use, have generated a plethora of data regarding male/female differences in the developing brain. Examination of these differences may shed light on the pathophysiology of the many illnesses that differ between the sexes and ultimately lead to more effective interventions. In this review, we attempt to synthesize the anatomic magnetic resonance imaging (MRI) literature of male/female brain differences with emphasis on studies encompassing adolescence - a time of divergence in physical and behavioral characteristics. Across all ages total brain size is consistently reported to be about 10% larger in males. Structures commonly reported to be different between sexes include the caudate nucleus, amygdala, hippocampus, and cerebellum - all noted to have a relatively high density of sex steroid receptors. The direction and magnitude of reported brain differences depends on the methodology of data acquisition and analysis, whether and how the subcomponents are adjusted for the total brain volume difference, and the age of the participants in the studies. Longitudinal studies indicate regional cortical gray matter volumes follow inverted U shaped developmental trajectories with peak size occurring one to three years earlier in females. Cortical gray matter differences are modulated by androgen receptor genotyope and by circulating levels of hormones. White matter volumes increase throughout childhood and adolescence in both sexes but more rapidly in adolescent males resulting in an expanding magnitude of sex differences from childhood to adulthood.
C1 [Giedd, Jay N.; Raznahan, Armin; Mills, Kathryn L.] NIMH, Child Psychiat Branch, Brain Imaging Unit, NIH, Bethesda, MD 20892 USA.
RP Giedd, JN (reprint author), NIMH, Child Psychiat Branch, Brain Imaging Unit, NIH, 10 Ctr Dr,MSC 1367,Bldg 10,Room 4 C110, Bethesda, MD 20892 USA.
EM jg@nih.gov
RI Raznahan, Armin/F-4534-2012; Giedd, Jay/J-9644-2015
OI Giedd, Jay/0000-0003-2002-8978
NR 104
TC 69
Z9 72
U1 4
U2 28
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 2042-6410
J9 BIOL SEX DIFFER
JI Biol. Sex Differ.
PD AUG 21
PY 2012
VL 3
AR 19
DI 10.1186/2042-6410-3-19
PG 9
WC Endocrinology & Metabolism; Genetics & Heredity
SC Endocrinology & Metabolism; Genetics & Heredity
GA 110CV
UT WOS:000316420600001
PM 22908911
ER
PT J
AU Tsourkas, PK
Das, SC
Yu-Yang, P
Liu, WL
Pierce, SK
Raychaudhuri, S
AF Tsourkas, Philippos K.
Das, Somkanya C.
Yu-Yang, Paul
Liu, Wanli
Pierce, Susan K.
Raychaudhuri, Subhadip
TI Formation of BCR oligomers provides a mechanism for B cell affinity
discrimination
SO JOURNAL OF THEORETICAL BIOLOGY
LA English
DT Article
DE Antigen; B cell receptor; Lymphocyte signaling; Lyn; Monte Carlo
ID RESPONSES IN-VIVO; SYNAPSE FORMATION; ANTIGEN RECEPTOR; LYMPH-NODE;
SUBCAPSULAR SINUS; DENDRITIC CELLS; T-CELLS; ACTIVATION; INITIATION;
THRESHOLD
AB B cells encounter antigen over a wide affinity range, from K-A=10(5) M-1 to K-A=10(10) M-1. The strength of B cell antigen receptor (BCR) signaling in response to antigen increases with affinity, a process known as "affinity discrimination". In this work, we use a computational simulation of B cell surface dynamics and membrane-proximal signaling to show that affinity discrimination can arise from the formation of BCR oligomers. It is known that BCRs form oligomers upon encountering antigen, and that the size and rate of formation of these oligomers both increase with affinity. In our simulation, we have introduced a requirement that only BCR-antigen complexes that are part of an oligomer can engage cytoplasmic signaling molecules such as Src-family kinases. Our simulation shows that as affinity increases, BCR signaling activity increases in addition to the number of collected antigen. Our results are also consistent with the existence of an experimentally-observed threshold affinity of activation at K-A=10(5)-10(6) M-1 (no signaling activity below this affinity value) and affinity discrimination ceiling of K-A=10(10) M-1 (no affinity discrimination above this affinity value). Comparison with experiments shows that the time scale of BCR oligomer formation predicted by our model (less than 10 s) is well within the time scale of experimentally observed association of BCR with Src-family kinases (10-20 s). (C) 2012 Elsevier Ltd. All rights reserved.
C1 [Tsourkas, Philippos K.; Das, Somkanya C.; Yu-Yang, Paul; Raychaudhuri, Subhadip] Univ Calif Davis, Dept Biomed Engn, Davis, CA 95616 USA.
[Liu, Wanli; Pierce, Susan K.] NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA.
RP Raychaudhuri, S (reprint author), Univ Calif Davis, Dept Biomed Engn, 1 Shields Ave, Davis, CA 95616 USA.
EM raychaudhuri@ucdavis.edu
RI liu, wanli/H-5690-2011; Tsourkas, Philippos/G-4026-2014;
OI liu, wanli/0000-0003-2624-6802; Raychaudhuri,
Subhadip/0000-0002-9873-6475
FU NIAID NIH HHS [R01 AI074022]
NR 39
TC 3
Z9 3
U1 1
U2 8
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0022-5193
J9 J THEOR BIOL
JI J. Theor. Biol.
PD AUG 21
PY 2012
VL 307
BP 174
EP 182
DI 10.1016/j.jtbi.2012.05.008
PG 9
WC Biology; Mathematical & Computational Biology
SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational
Biology
GA 974PD
UT WOS:000306447700018
PM 22613800
ER
PT J
AU Chen, Y
Wang, Y
Zhang, JZ
Deng, YQ
Jiang, L
Song, E
Wu, XFS
Hammer, JA
Xu, T
Lippincott-Schwartz, J
AF Chen, Yu
Wang, Yan
Zhang, Jinzhong
Deng, Yongqiang
Jiang, Li
Song, Eli
Wu, Xufeng S.
Hammer, John A.
Xu, Tao
Lippincott-Schwartz, Jennifer
TI Rab10 and myosin-Va mediate insulin-stimulated GLUT4 storage vesicle
translocation in adipocytes
SO JOURNAL OF CELL BIOLOGY
LA English
DT Article
ID GTPASE-ACTIVATING-PROTEIN; GLUCOSE-TRANSPORTER GLUT4; REGULATED
TRANSPORT; 3T3-L1 ADIPOCYTES; MEMBRANE; TRAFFICKING; AS160;
GLUCOSE-TRANSPORTER-4; EXOCYTOSIS; REQUIRES
AB Rab proteins are important regulators of insulin-stimulated GLUT4 translocation to the plasma membrane (PM), but the precise steps in GLUT4 trafficking modulated by particular Rab proteins remain unclear. Here, we systematically investigate the involvement of Rab proteins in GLUT4 trafficking, focusing on Rab proteins directly mediating GLUT4 storage vesicle (GSV) delivery to the PM. Using dual-color total internal reflection fluorescence (TIRF) microscopy and an insulin-responsive aminopeptidase (IRAP)-pHluorin fusion assay, we demonstrated that Rab10 directly facilitated GSV translocation to and docking at the PM. Rab14 mediated GLUT4 delivery to the PM via endosomal compartments containing transferrin receptor (TfR), whereas Rab4A, Rab4B, and Rab8A recycled GLUT4 through the endosomal system. Myosin-Va associated with GSVs by interacting with Rab10, positioning peripherally recruited GSVs for ultimate fusion. Thus, multiple Rab proteins regulate the trafficking of GLUT4, with Rab10 coordinating with myosin-Va to mediate the final steps of insulin-stimulated GSV translocation to the PM.
C1 [Chen, Yu; Lippincott-Schwartz, Jennifer] Eugene Kennedy Shriver Natl Inst Child Hlth & Hum, Cell Biol & Metab Program, NIH, Bethesda, MD 20892 USA.
[Wu, Xufeng S.; Hammer, John A.] NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA.
[Wang, Yan; Zhang, Jinzhong; Deng, Yongqiang; Jiang, Li; Song, Eli; Xu, Tao] Chinese Acad Sci, Inst Biophys, Beijing 100101, Peoples R China.
RP Lippincott-Schwartz, J (reprint author), Eugene Kennedy Shriver Natl Inst Child Hlth & Hum, Cell Biol & Metab Program, NIH, Bethesda, MD 20892 USA.
EM xutao@ibp.ac.cn; lippincj@mail.nih.gov
RI Chen, Yu/G-8724-2013; Zhang, Jinzhong/E-5670-2012
OI Zhang, Jinzhong/0000-0002-2540-2749
FU Major State Basic Research Program of the People's Republic of China
[2010CB833701]; National Science Foundation of China [30900268]; Beijing
Natural Science Foundation [5092017]
FX This work was supported by grants from the Major State Basic Research
Program of the People's Republic of China (2010CB833701), the National
Science Foundation of China (30900268), and the Beijing Natural Science
Foundation (5092017).
NR 42
TC 60
Z9 69
U1 0
U2 18
PU ROCKEFELLER UNIV PRESS
PI NEW YORK
PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA
SN 0021-9525
J9 J CELL BIOL
JI J. Cell Biol.
PD AUG 20
PY 2012
VL 198
IS 4
BP 545
EP 560
DI 10.1083/jcb.201111091
PG 16
WC Cell Biology
SC Cell Biology
GA 994LL
UT WOS:000307932200009
PM 22908308
ER
PT J
AU Hultcrantz, M
Kristinsson, SY
Andersson, TML
Landgren, O
Eloranta, S
Derolf, AR
Dickman, PW
Bjorkholm, M
AF Hultcrantz, Malin
Kristinsson, Sigurdur Yngvi
Andersson, Therese M. -L.
Landgren, Ola
Eloranta, Sandra
Derolf, Asa Rangert
Dickman, Paul W.
Bjorkholm, Magnus
TI Patterns of Survival Among Patients With Myeloproliferative Neoplasms
Diagnosed in Sweden From 1973 to 2008: A Population-Based Study
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID INTERNATIONAL WORKING GROUP; TYROSINE KINASE JAK2; ESSENTIAL
THROMBOCYTHEMIA; POLYCYTHEMIA-VERA; PRIMARY MYELOFIBROSIS; LIFE
EXPECTANCY; MYELOID METAPLASIA; PROGNOSTIC-FACTORS; CONSECUTIVE
PATIENTS; OLMSTED COUNTY
AB Purpose
Reported survival in patients with myeloproliferative neoplasms (MPNs) shows great variation. Patients with primary myelofibrosis (PMF) have substantially reduced life expectancy, whereas patients with polycythemia vera (PV) and essential thrombocythemia (ET) have moderately reduced survival in most, but not all, studies. We conducted a large population-based study to establish patterns of survival in more than 9,000 patients with MPNs.
Patients and Methods
We identified 9,384 patients with MPNs (from the Swedish Cancer Register) diagnosed from 1973 to 2008 (divided into four calendar periods) with follow-up to 2009. Relative survival ratios (RSRs) and excess mortality rate ratios were computed as measures of survival.
Results
Patient survival was considerably lower in all MPN subtypes compared with expected survival in the general population, reflected in 10-year RSRs of 0.64 (95% CI, 0.62 to 0.67) in patients with PV, 0.68 (95% CI, 0.64 to 0.71) in those with ET, and 0.21 (95% CI, 0.18 to 0.25) in those with PMF. Excess mortality was observed in patients with any MPN subtype during all four calendar periods (P < .001). Survival improved significantly over time (P < .001); however, the improvement was less pronounced after the year 2000 and was confined to patients with PV and ET.
Conclusion
We found patients with any MPN subtype to have significantly reduced life expectancy compared with the general population. The improvement over time is most likely explained by better overall clinical management of patients with MPN. The decreased life expectancy even in the most recent calendar period emphasizes the need for new treatment options for these patients.
C1 [Hultcrantz, Malin; Kristinsson, Sigurdur Yngvi; Landgren, Ola; Derolf, Asa Rangert; Bjorkholm, Magnus] Karolinska Univ Hosp, Stockholm, Sweden.
[Andersson, Therese M. -L.; Eloranta, Sandra; Dickman, Paul W.] Karolinska Inst, Stockholm, Sweden.
[Landgren, Ola] NCI, NIH, Bethesda, MD 20892 USA.
RP Hultcrantz, M (reprint author), Karolinska Univ Hosp Solna, Div Hematol, Dept Med, SE-17176 Stockholm, Sweden.
EM malin.hultcrantz@karolinska.se
RI Dickman, Paul/B-4572-2013; Kristinsson, Sigurdur /M-2910-2015;
Andersson, Therese/E-7107-2016
OI Dickman, Paul/0000-0002-5788-3380; Kristinsson, Sigurdur
/0000-0002-4964-7476; Andersson, Therese/0000-0001-8644-9041
FU Swedish Cancer Society [CAN 2009/1203]; Stockholm County Council [SLL
20090201]; Karolinska Institutet [SLL 20090201]; Karolinska Institutet
Foundations [2009Fobi0072]; Shire Pharmaceuticals; Adolf H. Lundin
Charitable Foundation
FX Supported by Grant No. CAN 2009/1203 from the Swedish Cancer Society; by
Grant No. SLL 20090201 from the regional agreement on medical training
and clinical research between Stockholm County Council and Karolinska
Institutet; by Grant No. 2009Fobi0072 from the Karolinska Institutet
Foundations; by an unrestricted grant from Shire Pharmaceuticals; and by
the Adolf H. Lundin Charitable Foundation.
NR 52
TC 52
Z9 53
U1 0
U2 2
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD AUG 20
PY 2012
VL 30
IS 24
BP 2995
EP 3001
DI 10.1200/JCO.2012.42.1925
PG 7
WC Oncology
SC Oncology
GA 996JR
UT WOS:000308082300015
PM 22802311
ER
PT J
AU Basch, E
Oliver, TK
Vickers, A
Thompson, I
Kantoff, P
Parnes, H
Loblaw, DA
Roth, B
Williams, J
Nam, RK
AF Basch, Ethan
Oliver, Thomas K.
Vickers, Andrew
Thompson, Ian
Kantoff, Philip
Parnes, Howard
Loblaw, D. Andrew
Roth, Bruce
Williams, James
Nam, Robert K.
TI Screening for Prostate Cancer With Prostate-Specific Antigen Testing:
American Society of Clinical Oncology Provisional Clinical Opinion
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID RANDOMIZED CONTROLLED-TRIAL; SERVICES-TASK-FORCE; FOLLOW-UP;
CONSERVATIVE MANAGEMENT; MORTALITY; COMPLICATIONS; STATISTICS; OUTCOMES;
BIOPSY; RISK
AB Purpose
An American Society of Clinical Oncology (ASCO) provisional clinical opinion (PCO) offers timely clinical direction to the ASCO membership after publication or presentation of potentially practice-changing data from major studies. This PCO addresses the role of prostate-specific antigen (PSA) testing in the screening of men for prostate cancer.
Clinical Context
Prostate cancer is the second leading cause of cancer deaths among men in the United States. The rationale for screening men for prostate cancer is the potential to reduce the risk of death through early detection. Recent Data Evidence from a 2011 Agency for Healthcare Research and Quality systematic review primarily informs this PCO on the benefits and harms of PSA-based screening. An update search was conducted to March 16, 2012, for additional evidence related to the topic.
Results
In one randomized trial, PSA testing in men who would not otherwise have been screened resulted in reduced death rates from prostate cancer, but it is uncertain whether the size of the effect was worth the harms associated with screening and subsequent unnecessary treatment. Although there are limitations to the existing data, there is evidence to suggest that men with longer life expectancy may benefit from PSA testing. Adverse events associated with prostate biopsy are low for the majority of men; however, several population-based studies have shown increasing rates of infectious complications after prostate biopsy, which is a concern.
C1 [Oliver, Thomas K.; Nam, Robert K.] Amer Soc Clin Oncol, Alexandria, VA 22314 USA.
[Basch, Ethan; Vickers, Andrew] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
[Thompson, Ian] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA.
[Kantoff, Philip] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA.
[Parnes, Howard] NCI, Rockville, MD USA.
[Loblaw, D. Andrew; Nam, Robert K.] Univ Toronto, Sunnybrook Hlth Sci Ctr, Odette Canc Ctr, Toronto, ON, Canada.
[Roth, Bruce] Washington Univ, St Louis, MO USA.
[Williams, James] Penn Prostate Canc Coalit, Camp Hill, PA USA.
RP Nam, RK (reprint author), Amer Soc Clin Oncol, 2318 Mill Rd,Suite 800, Alexandria, VA 22314 USA.
EM guidelines@asco.org
OI Vickers, Andrew/0000-0003-1525-6503
NR 46
TC 65
Z9 69
U1 0
U2 15
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD AUG 20
PY 2012
VL 30
IS 24
BP 3020
EP 3025
DI 10.1200/JCO.2012.43.3441
PG 6
WC Oncology
SC Oncology
GA 996JR
UT WOS:000308082300018
PM 22802323
ER
PT J
AU Kleinerman, RA
Yu, CL
Little, MP
Li, Y
Abramson, DH
Seddon, JM
Tucker, MA
AF Kleinerman, Ruth A.
Yu, Chu-Ling
Little, Mark P.
Li, Yi
Abramson, David H.
Seddon, Johanna M.
Tucker, Margaret A.
TI Risk Factors for the Incidence of Second Cancers in Survivors of
Retinoblastoma With a Family History Reply
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Letter
C1 [Kleinerman, Ruth A.; Little, Mark P.; Tucker, Margaret A.] NCI, NIH, Rockville, MD USA.
[Yu, Chu-Ling] Kaiser Permanente, Midatlantic Permanente Res Inst, Rockville, MD USA.
[Li, Yi] Univ Michigan, Sch Publ Hlth, Ann Arbor, MI 48109 USA.
[Abramson, David H.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
[Seddon, Johanna M.] Tufts Univ New England Med Ctr, Boston, MA USA.
RP Kleinerman, RA (reprint author), NCI, NIH, Rockville, MD USA.
RI Tucker, Margaret/B-4297-2015;
OI Kleinerman, Ruth/0000-0001-7415-2478
NR 4
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD AUG 20
PY 2012
VL 30
IS 24
BP 3028
EP 3029
DI 10.1200/JCO.2012.44.2657
PG 3
WC Oncology
SC Oncology
GA 996JR
UT WOS:000308082300021
ER
PT J
AU Wang, S
Shin, IS
Hancock, H
Jang, BS
Kim, HS
Lee, SM
Zderic, V
Frenkel, V
Pastan, I
Paik, CH
Dreher, MR
AF Wang, Shutao
Shin, In Soo
Hancock, Hilary
Jang, Beom-su
Kim, Hyung-sub
Lee, Sang Myung
Zderic, Vesna
Frenkel, Victor
Pastan, Ira
Paik, Chang H.
Dreher, Matthew R.
TI Pulsed high intensity focused ultrasound increases penetration and
therapeutic efficacy of monoclonal antibodies in murine xenograft tumors
SO JOURNAL OF CONTROLLED RELEASE
LA English
DT Article
DE Monoclonal antibodies; Pulsed-HIFU; Radioimmunotherapy; Penetration;
Binding site barrier
ID SOLID TUMORS; INTERSTITIAL PRESSURE; BREAST-CANCER; NANOPARTICLE
PENETRATION; CARCINOMA XENOGRAFTS; DELIVERY; RADIOIMMUNOTHERAPY;
MACROMOLECULES; ENHANCEMENT; MECHANISMS
AB The success of radioimmunotherapy for solid tumors remains elusive due to poor biodistribution and insufficient tumor accumulation, in part, due to the unique tumor microenvironment resulting in heterogeneous tumor antibody distribution. Pulsed high intensity focused ultrasound (pulsed-HIFU) has previously been shown to increase the accumulation of In-111 labeled B3 antibody (recognizes Lewis(y) antigen). The objective of this study was to investigate the tumor penetration and therapeutic efficacy of pulsed-HIFU exposures combined with Y-90 labeled B3 mAb in an A431 solid tumor model. The ability of pulsed-HIFU (1MHz, spatial averaged temporal peak intensity = 2685Wcm(-2); pulse repetition frequency=1Hz; duty cycle=5%) to improve the tumor penetration and therapeutic efficacy of Y-90 labeled B3 mAb (Y-90-B3) was evaluated in Le(y)-positive A431 tumors. Antibody penetration from the tumor surface and blood vessel surface was evaluated with fluorescently labeled B3, epi-fluorescent microscopy, and custom image analysis. Tumor size was monitored to determine treatment efficacy, indicated by survival, following various treatments with pulsed-HIFU and/or Y-90-B3. The pulsed-HIFU exposures did not affect the vascular parameters including microvascular density, vascular size, and vascular architecture; although 1.6-fold more antibody was delivered to the solid tumors when combined with pulsed-HIFU. The distribution and penetration of the antibodies were significantly improved (p-valueb0.05) when combined with pulsed-HIFU, only in the tumor periphery. Pretreatment with pulsed-HIFU significantly improved (p-valueb0.05) survival over control treatments. Published by Elsevier B. V.
C1 [Shin, In Soo; Jang, Beom-su; Kim, Hyung-sub; Lee, Sang Myung; Paik, Chang H.] NIH, Div Nucl Med, Dept Radiol & Imaging Sci, Ctr Clin, Bethesda, MD 20892 USA.
[Wang, Shutao; Zderic, Vesna] George Washington Univ, Dept Elect & Comp Engn, Washington, DC USA.
[Frenkel, Victor] Catholic Univ Amer, Dept Biomed Engn, Washington, DC 20064 USA.
[Pastan, Ira] NCI, NIH, Mol Biol Lab, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Dreher, MR (reprint author), NIH, Div Nucl Med, Dept Radiol & Imaging Sci, Ctr Clin, Bldg 10,Room 2N212 MSC1182, Bethesda, MD 20892 USA.
EM dreherm@cc.nih.gov
FU Intramural Research Program of the National Institutes of Health (NIH);
Center for Interventional Oncology; National Cancer Institute; Center
for Cancer Research
FX This research was supported by in part by the Intramural Research
Program of the National Institutes of Health (NIH), Center for
Interventional Oncology, National Cancer Institute, and Center for
Cancer Research. We thank Dr. Bradford J. Wood for his useful discussion
and support of this study.
NR 48
TC 22
Z9 23
U1 3
U2 34
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0168-3659
J9 J CONTROL RELEASE
JI J. Control. Release
PD AUG 20
PY 2012
VL 162
IS 1
BP 218
EP 224
DI 10.1016/j.jconrel.2012.06.025
PG 7
WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy
SC Chemistry; Pharmacology & Pharmacy
GA 992IP
UT WOS:000307769200026
PM 22732476
ER
PT J
AU Tyagi, RK
Garg, NK
Sahu, T
AF Tyagi, Rajeev K.
Garg, Neeraj K.
Sahu, Tejram
TI Vaccination Strategies against Malaria: novel carrier(s) more than a
tour de force
SO JOURNAL OF CONTROLLED RELEASE
LA English
DT Review
DE Hemagglutinin; Immunopotentiating reconstituted influenza virosomes;
pH-sensitive liposome; Cationic lipid; TAP (Transcription activator
protein); Transfection; Immunogenicity; Subunit vaccines; Adjuvant;
Microsphere; Virosomes
ID VACCINIA VIRUS ANKARA; RECONSTITUTED INFLUENZA VIROSOMES;
TRANSMISSION-BLOCKING IMMUNITY; PLASMODIUM-FALCIPARUM MALARIA;
C-TERMINAL FRAGMENT; FOWLPOX STRAIN FP9; T-CELL; GENE-DELIVERY;
CIRCUMSPOROZOITE PROTEIN; IN-VITRO
AB The introduction of vaccine technology has facilitated an unprecedented multi-antigen approach to develop an effective vaccine against complex systemic inflammatory pathogens such as Plasmodium spp. that cause severe malaria. The capacity of multi subunit DNA vaccine encoding different stage Plasmodium antigens to induce CD8(+) cytotoxic T lymphocytes and interferon-gamma responses in mice, monkeys and humans has been observed. Moreover, genetic vaccination may be capable of eliciting both cell mediated and humoral immune responses. The cytotoxic T cell responses are categorically needed against intracellular hepatic stage and humoral response with antibodies targeted against antigens from all stages of malaria parasite life cycle. Therefore, the key to success for any DNA based vaccine is to design a vector able to serve as a safe and efficient delivery system. This has encouraged the development of non-viral DNA-mediated gene transfer techniques such as liposome, virosomes, microsphere and nanoparticles. Efficient and relatively safe DNA transfection using lipoplexes makes them an appealing alternative to be explored for gene delivery. Also, liposome-entrapped DNA has been shown to enhance the potency of DNA vaccines, possibly by facilitating uptake of the plasmid by antigen-presenting cells (APC). Another recent technology using cationic lipids has been deployed and has generated substantial interest in this approach to gene transfer. In this review we discussed various aspects that could be decisive in the formulation of efficient and stable carrier system(s) for the development of malaria vaccine. Published by Elsevier B. V.
C1 [Tyagi, Rajeev K.] Univ S Florida, Coll Publ Hlth, Dept Global Hlth, Global Hlth Infect Dis Res Program, Tampa, FL 33612 USA.
[Garg, Neeraj K.] Dr Hari Singh Gour Vishwavidyalaya, Dept Pharmaceut Sci, Sagar 470003, MP, India.
[Garg, Neeraj K.] Sanofi Co, Shantha Biotechn Ltd, Res & Dev, Hyderabad 501401, Andhra Pradesh, India.
[Sahu, Tejram] NIAID, NIH, Rockville, MD USA.
RP Tyagi, RK (reprint author), Univ S Florida, Coll Publ Hlth, Dept Global Hlth, Global Hlth Infect Dis Res Program, 3720 Spectrum Blvd, Tampa, FL 33612 USA.
EM rtyagi@health.usf.edu
OI Sahu, Tejram/0000-0002-0912-7660
FU Department of Biotechnology; Council of Scientific and Industrial
Research; University Grant Commission, New Delhi, India
FX The research work is supported by various grants from Department of
Biotechnology, Council of Scientific and Industrial Research and
University Grant Commission, New Delhi, India. We are thankful to
analytical instrument facility of All India Institute of Medical
Sciences, New Delhi, India. The authors have no other relevant
affiliations or financial involvement with any organization or entity
with a financial interest in or financial conflict with the subject
matter or material discussed in the manuscript apart from those
disclosed. No writing assistance was utilized in the production of this
manuscript.
NR 167
TC 12
Z9 12
U1 1
U2 25
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0168-3659
J9 J CONTROL RELEASE
JI J. Control. Release
PD AUG 20
PY 2012
VL 162
IS 1
BP 242
EP 254
DI 10.1016/j.jconrel.2012.04.037
PG 13
WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy
SC Chemistry; Pharmacology & Pharmacy
GA 992IP
UT WOS:000307769200029
PM 22564369
ER
PT J
AU Rivero, MR
Miras, SL
Feliziani, C
Zamponi, N
Quiroga, R
Hayes, SF
Ropolo, AS
Touz, MC
AF Rivero, Maria R.
Miras, Silvana L.
Feliziani, Constanza
Zamponi, Nahuel
Quiroga, Rodrigo
Hayes, Stanley F.
Ropolo, Andrea S.
Touz, Maria C.
TI Vacuolar Protein Sorting Receptor in Giardia lamblia
SO PLOS ONE
LA English
DT Article
ID ACID-PHOSPHATASE-ACTIVITY; CRYSTALLOID ENDOPLASMIC-RETICULUM; COMBINED
TRANSMEMBRANE TOPOLOGY; SIGNAL PEPTIDE PREDICTION; CYST WALL PROTEINS;
PRIMITIVE EUKARYOTE; LEISHMANIA-DONOVANI; MEMBRANE-PROTEIN; SURFACE
PROTEIN; QUANTITATIVE-ANALYSIS
AB In Giardia, lysosome-like peripheral vacuoles (PVs) need to specifically coordinate their endosomal and lysosomal functions to be able to successfully perform endocytosis, protein degradation and protein delivery, but how cargo, ligands and molecular components generate specific routes to the PVs remains poorly understood. Recently, we found that delivering membrane Cathepsin C and the soluble acid phosphatase (AcPh) to the PVs is adaptin (AP1)-dependent. However, the receptor that links AcPh and AP1 was never described. We have studied protein-binding to AcPh by using H6-tagged AcPh, and found that a membrane protein interacted with AcPh. This protein, named GlVps (for Giardia lamblia Vacuolar protein sorting), mainly localized to the ER-nuclear envelope and in some PVs, probably functioning as the sorting receptor for AcPh. The tyrosine-binding motif found in the C-terminal cytoplasmic tail domain of GlVps was essential for its exit from the endoplasmic reticulum and transport to the vacuoles, with this motif being necessary for the interaction with the medium subunit of AP1. Thus, the mechanism by which soluble proteins, such as AcPh, reach the peripheral vacuoles in Giardia appears to be very similar to the mechanism of lysosomal protein-sorting in more evolved eukaryotic cells.
C1 [Rivero, Maria R.; Miras, Silvana L.; Feliziani, Constanza; Zamponi, Nahuel; Ropolo, Andrea S.; Touz, Maria C.] Univ Nacl Cordoba, Inst Invest Med Mercedes & Martin Ferreyra, RA-5000 Cordoba, Argentina.
[Quiroga, Rodrigo] Univ Nacl Cordoba, Fac Ciencias Quim, Dept Quim Biol, RA-5000 Cordoba, Argentina.
[Hayes, Stanley F.] NIAID, Rocky Mt Lab, NIH, Hamilton, MT 59840 USA.
RP Rivero, MR (reprint author), Univ Nacl Cordoba, Inst Invest Med Mercedes & Martin Ferreyra, RA-5000 Cordoba, Argentina.
EM ctouz@immf.uncor.edu
OI Quiroga, Rodrigo/0000-0001-5015-0531
FU Fogarty International Center [R01TW00724]; Argentine National Agency for
the Promotion of Science and Technology (FONCyT); National Council for
Sciences and Technology (CONICET)
FX The project was supported by Grant Number R01TW00724 from the Fogarty
International Center. The content is solely the responsibility of the
authors and does not necessarily represent the official views of the
Fogarty International Center or the National Institutes of Health. This
research was also supported in part by the Argentine National Agency for
the Promotion of Science and Technology (FONCyT), and the National
Council for Sciences and Technology (CONICET). The funders had no role
in study design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 85
TC 4
Z9 4
U1 1
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 20
PY 2012
VL 7
IS 8
AR e43712
DI 10.1371/journal.pone.0043712
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 991WJ
UT WOS:000307733800097
PM 22916299
ER
PT J
AU Anfinrud, P
Schotte, F
Cho, HS
Kataoka, M
Kamikubo, H
Kyndt, J
AF Anfinrud, Philip
Schotte, Friedrich
Cho, Hyun Sun
Kataoka, Mikio
Kamikubo, Hironari
Kyndt, John
TI Picosecond time-resolved X-ray studies of photactive yellow protein
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 244th National Fall Meeting of the American-Chemical-Society (ACS)
CY AUG 19-23, 2012
CL Philadelphia, PA
SP Amer Chem Soc, Div Hist Chem, Amer Chem Soc
C1 [Anfinrud, Philip; Schotte, Friedrich; Cho, Hyun Sun] NIH, Chem Phys Lab, Bethesda, MD 20892 USA.
[Kataoka, Mikio; Kamikubo, Hironari] NAIST, Nara, Japan.
[Kyndt, John] Univ Arizona, Dept Chem & Biochem, Tucson, AZ 85721 USA.
EM anfinrud@nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 1
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 19
PY 2012
VL 244
MA 311-PHYS
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 220XX
UT WOS:000324621807463
ER
PT J
AU Appella, DH
AF Appella, Daniel H.
TI Multivalent peptide nucleic acid nanoscaffolds that are precise,
programmable, and regulate cancer metastasis
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 244th National Fall Meeting of the American-Chemical-Society (ACS)
CY AUG 19-23, 2012
CL Philadelphia, PA
SP Amer Chem Soc, Div Hist Chem, Amer Chem Soc
C1 [Appella, Daniel H.] NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA.
EM appellad@niddk.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 1
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 19
PY 2012
VL 244
MA 711-ORGN
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 220XX
UT WOS:000324621807007
ER
PT J
AU Appella, DH
Jenkins, LM
Kumar, P
Wang, DY
Ott, DE
AF Appella, Daniel H.
Jenkins, Lisa M.
Kumar, Pankaj
Wang, Deyun
Ott, David E.
TI Inactivation of HIV-1 nucleocapsid NCp7 with a small molecule scaffold:
In vitro mechanism and in vivo efficacy
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 244th National Fall Meeting of the American-Chemical-Society (ACS)
CY AUG 19-23, 2012
CL Philadelphia, PA
SP Amer Chem Soc, Div Hist Chem, Amer Chem Soc
C1 [Appella, Daniel H.; Jenkins, Lisa M.; Kumar, Pankaj; Wang, Deyun; Ott, David E.] NIH, Bioorgan Chem Lab, Bethesda, MD 20892 USA.
EM appellad@niddk.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 19
PY 2012
VL 244
MA 23-MEDI
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 220XX
UT WOS:000324621805653
ER
PT J
AU Bhattacharyya, S
Wei, L
Riffle, L
Hill, GC
Jacobs, PM
Tatum, J
Doroshow, J
Kalen, J
AF Bhattacharyya, Sibaprasad
Wei, Ling
Riffle, Lisa
Hill, Gordon C.
Jacobs, Paula M.
Tatum, James
Doroshow, James
Kalen, Joseph
TI Immuno-PET with 89Zr labeled Panitumumab for the assessment of
HER1-expression level in carcinomas
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 244th National Fall Meeting of the American-Chemical-Society (ACS)
CY AUG 19-23, 2012
CL Philadelphia, PA
SP Amer Chem Soc, Div Hist Chem, Amer Chem Soc
C1 [Bhattacharyya, Sibaprasad; Wei, Ling] SAIC Frederick Natl Lab Canc Res, ADRD, Frederick, MD 21702 USA.
[Riffle, Lisa; Kalen, Joseph] SAIC Frederick Natl Lab Canc Res, SAIP, Frederick, MD 21702 USA.
[Hill, Gordon C.] SAIC Frederick Natl Lab Canc Res, CMRP, Frederick, MD 21702 USA.
[Jacobs, Paula M.; Tatum, James; Doroshow, James] NCI, DCTD, Bethesda, MD 20892 USA.
EM bhattacharyyas2@mail.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 19
PY 2012
VL 244
MA 96-NUCL
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 220XX
UT WOS:000324621806242
ER
PT J
AU Biswas, D
Saavedra, JE
Keefer, LK
Holland, RJ
Cao, Z
Deschamps, JR
AF Biswas, Debanjan
Saavedra, Joseph E.
Keefer, Larry K.
Holland, Ryan J.
Cao, Zhao
Deschamps, Jeffrey R.
TI O-2-Functionalized methylamine diazeniumdiolates as potential nitroxyl
prodrugs
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 244th National Fall Meeting of the American-Chemical-Society (ACS)
CY AUG 19-23, 2012
CL Philadelphia, PA
SP Amer Chem Soc, Div Hist Chem, Amer Chem Soc
C1 [Biswas, Debanjan; Saavedra, Joseph E.; Keefer, Larry K.; Holland, Ryan J.; Cao, Zhao] NCI, Drug Design Sect, Biol Chem Lab, Frederick, MD 21702 USA.
[Deschamps, Jeffrey R.] Naval Res Lab, Washington, DC 20375 USA.
EM biswasd@mail.nih.gov
NR 1
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 19
PY 2012
VL 244
MA 391-MEDI
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 220XX
UT WOS:000324621806113
ER
PT J
AU Bozza, WP
Yang, K
Wang, JL
Dexheimer, TS
Ngan, CH
Vajda, S
Simeonov, A
Zhuang, ZH
AF Bozza, William P.
Yang, Kun
Wang, Jialiang
Dexheimer, Thomas S.
Ngan, Chi Ho
Vajda, Sandor
Simeonov, Anton
Zhuang, Zhihao
TI Developing peptide-based multivalent antagonists of human proliferating
cell nuclear antigen
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 244th National Fall Meeting of the American-Chemical-Society (ACS)
CY AUG 19-23, 2012
CL Philadelphia, PA
SP Amer Chem Soc, Div Hist Chem, Amer Chem Soc
C1 [Bozza, William P.; Yang, Kun; Wang, Jialiang; Zhuang, Zhihao] Univ Delaware, Dept Chem & Biochem, Newark, DE 19716 USA.
[Dexheimer, Thomas S.; Simeonov, Anton] NHGRI, NIH, Chem Genom Ctr, Bethesda, MD 20892 USA.
[Ngan, Chi Ho; Vajda, Sandor] Boston Univ, Dept Biomed Engn, Boston, MA 02215 USA.
EM wbozza1@gmail.com
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 19
PY 2012
VL 244
MA 167-BIOL
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 220XX
UT WOS:000324621800729
ER
PT J
AU Brooks, BR
AF Brooks, Bernard R.
TI Recent techniques in CHARMM for exploring potential energy surfaces in
quantum chemistry involving complex QM/MM systems
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 244th National Fall Meeting of the American-Chemical-Society (ACS)
CY AUG 19-23, 2012
CL Philadelphia, PA
SP Amer Chem Soc, Div Hist Chem, Amer Chem Soc
C1 [Brooks, Bernard R.] NHLBI, Lab Computat Biol, Rockville, MD 20892 USA.
EM brb@nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 19
PY 2012
VL 244
MA 451-COMP
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 220XX
UT WOS:000324621803366
ER
PT J
AU Chen, YH
Tarasova, N
AF Chen, Yuhong
Tarasova, Nadya
TI Fully synthetic self-assembling virus-like nanoparticles targeting
prostate cancer cells
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 244th National Fall Meeting of the American-Chemical-Society (ACS)
CY AUG 19-23, 2012
CL Philadelphia, PA
SP Amer Chem Soc, Div Hist Chem, Amer Chem Soc
C1 [Chen, Yuhong; Tarasova, Nadya] Frederick Natl Lab Canc Res, Ctr Canc Res, Canc & Inflammat Program, Frederick, MD 21702 USA.
EM cheny8@mail.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 1
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 19
PY 2012
VL 244
MA 19-ORGN
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 220XX
UT WOS:000324621806271
ER
PT J
AU Daniel, MC
Ghann, WE
Aras, O
Fleiter, T
AF Daniel, Marie-Christine
Ghann, William E.
Aras, Omer
Fleiter, Thorsten
TI Lisinopril-coated gold nanoparticles as targeted CT nanoprobes for
monitoring of cardiovascular diseases
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 244th National Fall Meeting of the American-Chemical-Society (ACS)
CY AUG 19-23, 2012
CL Philadelphia, PA
SP Amer Chem Soc, Div Hist Chem, Amer Chem Soc
C1 [Daniel, Marie-Christine; Ghann, William E.] Univ Maryland Baltimore Cty, Dept Chem & Biochem, Baltimore, MD 21250 USA.
[Aras, Omer] NIH, Dept Radiol & Imaging Sci, Bethesda, MD 20892 USA.
[Aras, Omer] NIH, Mol Imaging Program, Bethesda, MD 20892 USA.
[Fleiter, Thorsten] Univ Maryland Med Syst, Dept Radiol, Baltimore, MD 21201 USA.
EM mdaniel@umbc.edu
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 19
PY 2012
VL 244
MA 388-COLL
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 220XX
UT WOS:000324621802574
ER
PT J
AU Dix, AV
AF Dix, Andrew V.
TI Probing adenosine A2A receptor multivalency using peptide nucleic acid
based nanoscaffolds
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 244th National Fall Meeting of the American-Chemical-Society (ACS)
CY AUG 19-23, 2012
CL Philadelphia, PA
SP Amer Chem Soc, Div Hist Chem, Amer Chem Soc
C1 [Dix, Andrew V.] NIH, Biol Chem Lab, Bethesda, MD 20892 USA.
EM Andrew.Dix@NIH.GOV
NR 0
TC 0
Z9 0
U1 0
U2 1
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 19
PY 2012
VL 244
MA 710-ORGN
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 220XX
UT WOS:000324621807006
ER
PT J
AU Englund, EA
Micklitsch, CM
Onyshchenko, MI
Neumann, RD
Panyutin, IG
Appella, DH
AF Englund, Ethan A.
Micklitsch, Christopher M.
Onyshchenko, Mykola I.
Neumann, Ronald D.
Panyutin, Igor G.
Appella, Daniel H.
TI Targeting DNA G-quadruplex structures with pyrazolo[3,4-d]pyrimidine
guanine PNA oligomers
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 244th National Fall Meeting of the American-Chemical-Society (ACS)
CY AUG 19-23, 2012
CL Philadelphia, PA
SP Amer Chem Soc, Div Hist Chem, Amer Chem Soc
C1 [Englund, Ethan A.; Micklitsch, Christopher M.; Appella, Daniel H.] NIDDK, Lab Bioorgan Chemsitry, NIH, Bethesda, MD 20814 USA.
[Onyshchenko, Mykola I.; Neumann, Ronald D.; Panyutin, Igor G.] NIH, Dept Radiol & Imaging Sci, Ctr Clin, Bethesda, MD 20892 USA.
[Onyshchenko, Mykola I.] NIBIB, Imaging Sci Training Program, NIH, Bethesda, MD 20892 USA.
EM englunde@niddk.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 1
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 19
PY 2012
VL 244
MA 755-ORGN
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 220XX
UT WOS:000324621807042
ER
PT J
AU Fawzi, NL
Ying, JF
Torchia, DA
Clore, GM
AF Fawzi, Nicolas L.
Ying, Jinfa
Torchia, Dennis A.
Clore, G. Marius
TI Dyanamics on the surface of amyloid-beta protofibrils in solution:
Dark-state exchange saturation transfer NMR
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 244th National Fall Meeting of the American-Chemical-Society (ACS)
CY AUG 19-23, 2012
CL Philadelphia, PA
SP Amer Chem Soc, Div Hist Chem, Amer Chem Soc
C1 [Fawzi, Nicolas L.; Ying, Jinfa; Clore, G. Marius] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
[Torchia, Dennis A.] NIDCR, NIH, Bethesda, MD 20892 USA.
EM fawzin@helix.nih.gov
RI Clore, G. Marius/A-3511-2008
OI Clore, G. Marius/0000-0003-3809-1027
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 19
PY 2012
VL 244
MA 225-PHYS
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 220XX
UT WOS:000324621807380
ER
PT J
AU Gangjee, A
Pavana, RK
Ihnat, MA
Hamel, E
AF Gangjee, Aleem
Pavana, Roheeth Kumar
Ihnat, Michael A.
Hamel, Ernest
TI Design, synthesis, and preclinical evaluation of 7-benzyl -N-substituted
phenyl-5H-pyrrolo[3,2-d]pyrimidin-4-amines as single agents with
antitubulin and antiangiogenic activity as antitumor agents
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 244th National Fall Meeting of the American-Chemical-Society (ACS)
CY AUG 19-23, 2012
CL Philadelphia, PA
SP Amer Chem Soc, Div Hist Chem, Amer Chem Soc
C1 [Gangjee, Aleem; Pavana, Roheeth Kumar] Duquesne Univ, Grad Sch Pharmaceut Sci, Div Med Chem, Pittsburgh, PA 15282 USA.
[Ihnat, Michael A.] Univ Oklahoma, Hlth Sci Ctr, Coll Pharm, Dept Pharmaceut Sci, Oklahoma City, OK 73117 USA.
[Hamel, Ernest] NCI, Screening Technol Branch, Dev Therapeut Program, Div Canc Treatment & Diag,Frederick Natl Lab Canc, Frederick, MD 21702 USA.
EM kp.roheeth@gmail.com
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 19
PY 2012
VL 244
MA 321-MEDI
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 220XX
UT WOS:000324621806049
ER
PT J
AU Gangjee, A
Devambatla, RKV
Choudhary, S
Bai, R
Hamel, E
AF Gangjee, Aleem
Devambatla, Ravi Kumar Vyas
Choudhary, Shruti
Bai, Ruoli
Hamel, Ernest
TI Design, synthesis, and biological evaluation of substituted
furo[2,3-d]pyrimidines as potent antimitotic agents that circumvent Pgp
and bIII-tubulin mediated resistance
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 244th National Fall Meeting of the American-Chemical-Society (ACS)
CY AUG 19-23, 2012
CL Philadelphia, PA
SP Amer Chem Soc, Div Hist Chem, Amer Chem Soc
C1 [Gangjee, Aleem; Devambatla, Ravi Kumar Vyas; Choudhary, Shruti] Duquesne Univ, Div Med Chem, Pittsburgh, PA 15282 USA.
[Bai, Ruoli; Hamel, Ernest] Frederick Natl Lab Canc Res, Div Canc Treatment & Diag, Frederick, MD 21702 USA.
EM drk_vyas@yahoo.co.in
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 19
PY 2012
VL 244
MA 320-MEDI
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 220XX
UT WOS:000324621806048
ER
PT J
AU Garcia, CL
Marquez, VE
Comin, MJ
AF Garcia, Cynthia L.
Marquez, Victor E.
Comin, Maria J.
TI Synthesis of N-methylsubstituted indololactones as selective activators
of Ras guanyl nucleotide-release proteins (RasGRP)
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 244th National Fall Meeting of the American-Chemical-Society (ACS)
CY AUG 19-23, 2012
CL Philadelphia, PA
SP Amer Chem Soc, Div Hist Chem, Amer Chem Soc
C1 [Garcia, Cynthia L.; Comin, Maria J.] Inst Nacl Tecnol Ind, Dept Chem, Buenos Aires, DF, Argentina.
[Marquez, Victor E.] NIH, Biol Chem Lab, Ctr Canc Res, Ft Detrick, MD 21702 USA.
EM cgarcia@inti.gob.ar
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 19
PY 2012
VL 244
MA 302-MEDI
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 220XX
UT WOS:000324621806031
ER
PT J
AU Giano, MC
Schneider, JP
AF Giano, Michael C.
Schneider, Joel P.
TI Controlled degradation of self-assembled b-hairpin hydrogels by
proteolysis with matrix metalloproteinase-13
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 244th National Fall Meeting of the American-Chemical-Society (ACS)
CY AUG 19-23, 2012
CL Philadelphia, PA
SP Amer Chem Soc, Div Hist Chem, Amer Chem Soc
C1 [Giano, Michael C.; Schneider, Joel P.] NCI, Dept Biol Chem, Frederick, MD 21701 USA.
[Giano, Michael C.] Univ Delaware, Dept Chem & Biochem, Newark, DE 19711 USA.
EM gianomc@mail.nih.gov
NR 0
TC 0
Z9 0
U1 2
U2 4
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 19
PY 2012
VL 244
MA 222-POLY
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 220XX
UT WOS:000324621808391
ER
PT J
AU Gildersleeve, J
AF Gildersleeve, Jeffrey
TI Antiglycan antibodies as biomarkers for personalized medicine
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 244th National Fall Meeting of the American-Chemical-Society (ACS)
CY AUG 19-23, 2012
CL Philadelphia, PA
SP Amer Chem Soc, Div Hist Chem, Amer Chem Soc
C1 [Gildersleeve, Jeffrey] NCI, Biol Chem Lab, Frederick, MD 21702 USA.
EM gildersj@mail.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 19
PY 2012
VL 244
MA 86-CARB
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 220XX
UT WOS:000324621801239
ER
PT J
AU Gupta, P
Appella, DH
AF Gupta, Pankaj
Appella, Daniel H.
TI Synthesis of pyrrole derivatives for selective inhibition of Wip-1
phosphatase
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 244th National Fall Meeting of the American-Chemical-Society (ACS)
CY AUG 19-23, 2012
CL Philadelphia, PA
SP Amer Chem Soc, Div Hist Chem, Amer Chem Soc
C1 [Gupta, Pankaj; Appella, Daniel H.] NIDDK, NIH, Bethesda, MD 20892 USA.
EM kumarp5@mail.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 2
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 19
PY 2012
VL 244
MA 41-MEDI
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 220XX
UT WOS:000324621805669
ER
PT J
AU Hassink, MD
Appella, D
AF Hassink, Matthew D.
Appella, Daniel
TI Synthesis of small molecule ligands and their expression in a
multivalent sense on a PNA scaffold
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 244th National Fall Meeting of the American-Chemical-Society (ACS)
CY AUG 19-23, 2012
CL Philadelphia, PA
SP Amer Chem Soc, Div Hist Chem, Amer Chem Soc
C1 [Hassink, Matthew D.; Appella, Daniel] NIDDK, Bethesda, MD 20892 USA.
EM matthew.hassink@nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 2
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 19
PY 2012
VL 244
MA 758-ORGN
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 220XX
UT WOS:000324621807045
ER
PT J
AU Hogan, M
Bahta, M
Zhao, B
Cherry, S
Tropea, JE
Lountos, GT
Burke, TR
Waugh, DS
Ulrich, RG
AF Hogan, Megan
Bahta, Medhanit
Zhao, Bryan
Cherry, Scott
Tropea, Joseph E.
Lountos, George T.
Burke, Terrence R.
Waugh, David S.
Ulrich, Robert G.
TI Investigation of the interaction kinetics between small molecule
inhibitors and the protein tyrosine phosphatase YopH from Yersinia
pestis
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 244th National Fall Meeting of the American-Chemical-Society (ACS)
CY AUG 19-23, 2012
CL Philadelphia, PA
SP Amer Chem Soc, Div Hist Chem, Amer Chem Soc
C1 [Hogan, Megan; Zhao, Bryan] Oak Ridge Associated Univ, Fac Res Participat Program, Belcamp, MD 21017 USA.
[Hogan, Megan; Zhao, Bryan; Ulrich, Robert G.] US Army Med Res Inst Infect Dis, Lab Mol Immunol, Frederick, MD 21702 USA.
[Bahta, Medhanit; Burke, Terrence R.] NCI, Biol Chem Lab, Ctr Canc Res, NIH,Frederick Natl Lab, Frederick, MD 21702 USA.
[Cherry, Scott; Tropea, Joseph E.; Lountos, George T.; Waugh, David S.] NCI, Macromol Crystallog Lab, Ctr Canc Res, NIH,Frederick Natl Lab, Frederick, MD 21702 USA.
RI Lountos, George/B-3983-2015
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 19
PY 2012
VL 244
MA 402-MEDI
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 220XX
UT WOS:000324621806124
ER
PT J
AU Horkay, F
Basser, PJ
Hecht, AM
Geissler, E
AF Horkay, Ferenc
Basser, Peter J.
Hecht, Anne-Marie
Geissler, Erik
TI Hierarchy and organization of hyaluronic acid in physiological salt
solutions
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 244th National Fall Meeting of the American-Chemical-Society (ACS)
CY AUG 19-23, 2012
CL Philadelphia, PA
SP Amer Chem Soc, Div Hist Chem, Amer Chem Soc
C1 [Horkay, Ferenc; Basser, Peter J.] NICHD, NIH, Bethesda, MD 20892 USA.
[Hecht, Anne-Marie; Geissler, Erik] Univ J Fourier Grenoble, Spectrometrie Phys Lab, St Martin Dheres, France.
EM horkay@helix.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 1
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 19
PY 2012
VL 244
MA 186-PMSE
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 220XX
UT WOS:000324621807850
ER
PT J
AU Horkay, F
Horkayne-Szakaly, I
Dimitriadis, EK
Silva, C
Basser, PJ
AF Horkay, Ferenc
Horkayne-Szakaly, Iren
Dimitriadis, Emilios K.
Silva, Candida
Basser, Peter J.
TI Cartilage: Structure and osmotic properties
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 244th National Fall Meeting of the American-Chemical-Society (ACS)
CY AUG 19-23, 2012
CL Philadelphia, PA
SP Amer Chem Soc, Div Hist Chem, Amer Chem Soc
C1 [Horkay, Ferenc; Horkayne-Szakaly, Iren; Silva, Candida; Basser, Peter J.] NICHD, NIH, Bethesda, MD 20892 USA.
[Dimitriadis, Emilios K.] NIBIB, NIH, Bethesda, MD 20892 USA.
EM horkay@helix.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 1
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 19
PY 2012
VL 244
MA 202-BIOL
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 220XX
UT WOS:000324621800755
ER
PT J
AU Hu, X
Southall, N
Barnaeva, E
Bryant-Genevier, M
Titus, S
Xiao, JB
Ferrer, M
Marugan, J
Free, RB
Sibley, DR
AF Hu, Xin
Southall, Noel
Barnaeva, Elena
Bryant-Genevier, Melanie
Titus, Steve
Xiao, Jingbo
Ferrer, Marc
Marugan, Juan
Free, R. Benjamin
Sibley, David R.
TI Modeling and virtual screening of the D-2 dopamine receptor
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 244th National Fall Meeting of the American-Chemical-Society (ACS)
CY AUG 19-23, 2012
CL Philadelphia, PA
SP Amer Chem Soc, Div Hist Chem, Amer Chem Soc
C1 [Hu, Xin; Southall, Noel; Barnaeva, Elena; Bryant-Genevier, Melanie; Titus, Steve; Xiao, Jingbo; Ferrer, Marc; Marugan, Juan] NIH, Natl Ctr Adv Translat Sci, Rockville, MD 20850 USA.
[Free, R. Benjamin; Sibley, David R.] NINDS, NIH, Rockville, MD 20850 USA.
EM hux61@mail.nih.gov
NR 0
TC 0
Z9 0
U1 1
U2 1
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 19
PY 2012
VL 244
MA 310-COMP
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 220XX
UT WOS:000324621803248
ER
PT J
AU Hummer, G
Zhu, FQ
AF Hummer, Gerhard
Zhu, Fangqiang
TI Water fluctuations in the hydrophobic gate of an ion channel
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 244th National Fall Meeting of the American-Chemical-Society (ACS)
CY AUG 19-23, 2012
CL Philadelphia, PA
SP Amer Chem Soc, Div Hist Chem, Amer Chem Soc
C1 [Hummer, Gerhard] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
[Zhu, Fangqiang] Indiana Univ Purdue Univ, Dept Phys, Indianapolis, IN 46202 USA.
EM gerhard.hummer@nih.gov
RI Hummer, Gerhard/A-2546-2013
OI Hummer, Gerhard/0000-0001-7768-746X
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 19
PY 2012
VL 244
MA 57-PHYS
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 220XX
UT WOS:000324621807221
ER
PT J
AU Hummer, G
Rozycki, B
Kim, YC
AF Hummer, Gerhard
Rozycki, Bartosz
Kim, Young C.
TI Structure and dynamics of multiprotein assemblies from simulation and
experiment
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 244th National Fall Meeting of the American-Chemical-Society (ACS)
CY AUG 19-23, 2012
CL Philadelphia, PA
SP Amer Chem Soc, Div Hist Chem, Amer Chem Soc
C1 [Hummer, Gerhard] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
[Rozycki, Bartosz] Max Planck Inst Colloids & Interfaces, Dept Theory & Biosyst, Potsdam, Germany.
[Kim, Young C.] Naval Res Lab, Ctr Computat Mat Sci, Washington, DC 20375 USA.
EM gerhard.hummer@nih.gov
RI Rozycki, Bartosz/B-7005-2009; Hummer, Gerhard/A-2546-2013
OI Rozycki, Bartosz/0000-0001-5938-7308; Hummer,
Gerhard/0000-0001-7768-746X
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 19
PY 2012
VL 244
MA 248-COMP
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 220XX
UT WOS:000324621803189
ER
PT J
AU Jacobson, KA
AF Jacobson, Kenneth A.
TI Structure-based discovery of novel ligands of GPCRs: Adenosine receptors
and P2Y receptors
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 244th National Fall Meeting of the American-Chemical-Society (ACS)
CY AUG 19-23, 2012
CL Philadelphia, PA
SP Amer Chem Soc, Div Hist Chem, Amer Chem Soc
C1 [Jacobson, Kenneth A.] NIDDK, Mol Recognit Sect, Bioorgan Chem Lab, Bethesda, MD 20892 USA.
EM kajacobs@helix.nih.gov
RI Jacobson, Kenneth/A-1530-2009
OI Jacobson, Kenneth/0000-0001-8104-1493
NR 0
TC 0
Z9 0
U1 2
U2 2
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 19
PY 2012
VL 244
MA 241-MEDI
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 220XX
UT WOS:000324621805861
ER
PT J
AU Jayasekara, MPS
Barchi, JJ
Phan, K
Kumar, TS
Zhang, GF
Tosh, DK
Gao, ZG
Jacobson, KA
AF Jayasekara, M. P. Suresh
Barchi, Joseph J.
Phan, Khai
Kumar, T. Santhosh
Zhang, Guofeng
Tosh, Dilip K.
Gao, Zhan-Guo
Jacobson, Kenneth A.
TI Design of adenosine receptor agonist- and antagonist-conjugated gold
nanoparticles for therapeutic applications including cancer
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 244th National Fall Meeting of the American-Chemical-Society (ACS)
CY AUG 19-23, 2012
CL Philadelphia, PA
SP Amer Chem Soc, Div Hist Chem, Amer Chem Soc
C1 [Jayasekara, M. P. Suresh; Phan, Khai; Kumar, T. Santhosh; Tosh, Dilip K.; Gao, Zhan-Guo; Jacobson, Kenneth A.] NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA.
[Barchi, Joseph J.] NCI, Biol Chem Lab, Frederick, MD 21702 USA.
[Zhang, Guofeng] Biomed Engn & Phys Sci Shared Resource NIBIB, NIH, Bethesda, MD 20892 USA.
EM pushpa.mudiyanselage@nih.gov
RI Jacobson, Kenneth/A-1530-2009
OI Jacobson, Kenneth/0000-0001-8104-1493
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 19
PY 2012
VL 244
MA 49-MEDI
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 220XX
UT WOS:000324621805677
ER
PT J
AU Jin, AJ
Sackett, DL
Lafer, EM
Smith, PD
Nossal, R
AF Jin, Albert J.
Sackett, Dan L.
Lafer, Eileen M.
Smith, Paul D.
Nossal, Ralph
TI Assessing clathrin-clathrin interactions and clathrin hair-pin folds by
atomic force spectroscopy
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 244th National Fall Meeting of the American-Chemical-Society (ACS)
CY AUG 19-23, 2012
CL Philadelphia, PA
SP Amer Chem Soc, Div Hist Chem, Amer Chem Soc
C1 [Jin, Albert J.; Smith, Paul D.] Natl Inst Biomed Imaging & Bioengn, Lab Cellular Imaging & Macromol Biophys, Bethesda, MD 20892 USA.
[Sackett, Dan L.; Nossal, Ralph] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Lab Integrat & Med Biophys, Bethesda, MD 20892 USA.
[Lafer, Eileen M.] Univ Texas Hlth Sci Ctr San Antonio, Dept Biochem, San Antonio, TX 78229 USA.
EM ajjin@helix.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 19
PY 2012
VL 244
MA 154-BIOL
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 220XX
UT WOS:000324621800718
ER
PT J
AU Kabir, MS
Peng, YF
Jacobson, AE
Rice, KC
AF Kabir, M. Shahjahan
Peng, Yuefeng
Jacobson, Arthur E.
Rice, Kenner C.
TI Probes for narcotic receptor mediated phenomena: Examination of the
large-scale synthesis of C-8-substituted 5-phenylmorphans
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 244th National Fall Meeting of the American-Chemical-Society (ACS)
CY AUG 19-23, 2012
CL Philadelphia, PA
SP Amer Chem Soc, Div Hist Chem, Amer Chem Soc
C1 [Kabir, M. Shahjahan; Peng, Yuefeng; Jacobson, Arthur E.; Rice, Kenner C.] NIDA, NIH, Rockville, MD 20852 USA.
EM kabirms@mail.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 19
PY 2012
VL 244
MA 562-ORGN
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 220XX
UT WOS:000324621806762
ER
PT J
AU Kaila, VRI
Hummer, G
AF Kaila, Ville R. I.
Hummer, Gerhard
TI Energetics of direct and water mediated proton-coupled electron transfer
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 244th National Fall Meeting of the American-Chemical-Society (ACS)
CY AUG 19-23, 2012
CL Philadelphia, PA
SP Amer Chem Soc, Div Hist Chem, Amer Chem Soc
C1 [Kaila, Ville R. I.; Hummer, Gerhard] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
EM ville.kaila@nih.gov
RI Hummer, Gerhard/A-2546-2013
OI Hummer, Gerhard/0000-0001-7768-746X
NR 0
TC 0
Z9 0
U1 0
U2 1
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 19
PY 2012
VL 244
MA 239-COMP
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 220XX
UT WOS:000324621803181
ER
PT J
AU Kim, S
Bolton, EE
Bryant, SH
AF Kim, Sunghwan
Bolton, Evan E.
Bryant, Stephen H.
TI Statistical significance of 3D molecular similarity scores
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 244th National Fall Meeting of the American-Chemical-Society (ACS)
CY AUG 19-23, 2012
CL Philadelphia, PA
SP Amer Chem Soc, Div Hist Chem, Amer Chem Soc
C1 [Kim, Sunghwan; Bolton, Evan E.; Bryant, Stephen H.] NIH, Natl Lib Med, Bethesda, MD 20894 USA.
EM kimsungh@ncbi.nlm.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 2
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 19
PY 2012
VL 244
MA 137-CINF
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 220XX
UT WOS:000324621802198
ER
PT J
AU Konig, G
Miller, BT
Boresch, S
Wu, XW
Brooks, BR
AF Koenig, Gerhard
Miller, Benjamin T.
Boresch, Stefan
Wu, Xiongwu
Brooks, Bernard R.
TI Enhanced sampling in free energy calculations
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 244th National Fall Meeting of the American-Chemical-Society (ACS)
CY AUG 19-23, 2012
CL Philadelphia, PA
SP Amer Chem Soc, Div Hist Chem, Amer Chem Soc
C1 [Koenig, Gerhard; Miller, Benjamin T.; Wu, Xiongwu; Brooks, Bernard R.] NHLBI, Lab Computat Biol, NIH, Rockville, MD 20852 USA.
[Boresch, Stefan] Univ Vienna, Dept Computat Biol Chem, Vienna, Austria.
EM gerhard.koenig@nih.gov
RI Boresch, Stefan/F-3467-2014
OI Boresch, Stefan/0000-0002-2793-6656
NR 0
TC 0
Z9 0
U1 0
U2 1
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 19
PY 2012
VL 244
MA 347-COMP
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 220XX
UT WOS:000324621803278
ER
PT J
AU Kraft, ML
Frisz, JF
Klitzing, HA
Lou, KY
Lizunov, V
Carpenter, KJ
Weber, PK
Zimmerberg, J
AF Kraft, Mary L.
Frisz, Jessica F.
Klitzing, Haley A.
Lou, Kaiyan
Lizunov, Vladimir
Carpenter, Kevin J.
Weber, Peter K.
Zimmerberg, Joshua
TI Imaging the sphingolipid and cholesterol distribution in the plasma
membrane using secondary ion mass spectrometry
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 244th National Fall Meeting of the American-Chemical-Society (ACS)
CY AUG 19-23, 2012
CL Philadelphia, PA
SP Amer Chem Soc, Div Hist Chem, Amer Chem Soc
C1 [Kraft, Mary L.; Lou, Kaiyan] Univ Illinois, Dept Chem & Biomol Engn, Urbana, IL 61801 USA.
[Kraft, Mary L.; Frisz, Jessica F.; Klitzing, Haley A.] Univ Illinois, Dept Chem, Urbana, IL 61801 USA.
[Lizunov, Vladimir; Zimmerberg, Joshua] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Phys Biol, Bethesda, MD 20892 USA.
[Carpenter, Kevin J.; Weber, Peter K.] Lawrence Livermore Natl Lab, Glenn T Seaborg Inst, Livermore, CA 94511 USA.
EM mlkraft@illinois.edu
NR 0
TC 0
Z9 0
U1 1
U2 3
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 19
PY 2012
VL 244
MA 236-ANYL
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 220XX
UT WOS:000324621801100
ER
PT J
AU Lee, J
Bhondwe, RS
Kang, DW
Kim, MS
Kim, HS
Park, SG
Son, K
Choi, S
Kuhs, KAL
Pavlyukovets, VA
Pearce, LV
Blumberg, PM
AF Lee, Jeewoo
Bhondwe, Rahul S.
Kang, Dong Wook
Kim, Myeong Seop
Kim, Ho Shin
Park, Seul-gi
Son, Karam
Choi, Sun
Kuhs, Krystle A. Lang
Pavlyukovets, Vladimir A.
Pearce, Larry V.
Blumberg, Peter M.
TI Structure activity relationships and molecular modeling of the
N-(3-pivaloyloxy-2-benzylpropyl)-N '-[4-(methylsulfonylamino)benzyl]
thiourea template for TRPV1 antagonism
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 244th National Fall Meeting of the American-Chemical-Society (ACS)
CY AUG 19-23, 2012
CL Philadelphia, PA
SP Amer Chem Soc, Div Hist Chem, Amer Chem Soc
C1 [Lee, Jeewoo; Bhondwe, Rahul S.; Kang, Dong Wook; Kim, Myeong Seop; Kim, Ho Shin] Seoul Natl Univ, Coll Pharm, Seoul, South Korea.
[Park, Seul-gi; Son, Karam; Choi, Sun] Ewha Womans Univ, Coll Pharm, Seoul, South Korea.
[Kuhs, Krystle A. Lang; Pavlyukovets, Vladimir A.; Pearce, Larry V.; Blumberg, Peter M.] NCI, Lab Canc Biol & Genet, Bethesda, MD 20892 USA.
EM jeewoo@snu.ac.kr
NR 0
TC 0
Z9 0
U1 0
U2 2
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 19
PY 2012
VL 244
MA 376-MEDI
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 220XX
UT WOS:000324621806099
ER
PT J
AU Lucas, HR
AF Lucas, Heather R.
TI Amyloids and copper biochemistry: Effects of metal dyshomeostasis in
Alzheimer's and Parkinson's disease
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 244th National Fall Meeting of the American-Chemical-Society (ACS)
CY AUG 19-23, 2012
CL Philadelphia, PA
SP Amer Chem Soc, Div Hist Chem, Amer Chem Soc
C1 [Lucas, Heather R.] NIA, NIH, Baltimore, MD 21224 USA.
EM lucash@mail.nih.gov
NR 0
TC 0
Z9 0
U1 1
U2 4
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 19
PY 2012
VL 244
MA 39-AEI
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 220XX
UT WOS:000324621800037
ER
PT J
AU Mallajosyula, SS
Barchi, JJ
Adams, KM
MacKerell, AD
AF Mallajosyula, Sairam S.
Barchi, Joseph J.
Adams, Kristie M.
MacKerell, Alexander D., Jr.
TI Structure-activity studies on antiproliferative factor (APF)
glycopeptide derivatives
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 244th National Fall Meeting of the American-Chemical-Society (ACS)
CY AUG 19-23, 2012
CL Philadelphia, PA
SP Amer Chem Soc, Div Hist Chem, Amer Chem Soc
C1 [Mallajosyula, Sairam S.; MacKerell, Alexander D., Jr.] Univ Maryland, Sch Pharm, Dept Pharmaceut Sci, Baltimore, MD 21201 USA.
[Barchi, Joseph J.; Adams, Kristie M.] NCI, Biol Chem Lab, Mol Discovery Program, Ctr Canc Res, Frederick, MD 21702 USA.
EM sairam.umb@gmail.com
NR 0
TC 0
Z9 0
U1 0
U2 1
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 19
PY 2012
VL 244
MA 333-COMP
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 220XX
UT WOS:000324621803266
ER
PT J
AU Mayer, ML
AF Mayer, Mark L.
TI Crystallographic studies on glutamate receptor ligand binding domains
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 244th National Fall Meeting of the American-Chemical-Society (ACS)
CY AUG 19-23, 2012
CL Philadelphia, PA
SP Amer Chem Soc, Div Hist Chem, Amer Chem Soc
C1 [Mayer, Mark L.] NIH, Lab Cellular & Mol Neurophysiol, Bethesda, MD 20892 USA.
EM mayerm@mail.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 19
PY 2012
VL 244
MA 206-MEDI
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 220XX
UT WOS:000324621805827
ER
PT J
AU Miller, B
Woodcock, HL
Brooks, B
AF Miller, Benjamin
Woodcock, Henry Lee
Brooks, Bernard
TI Novel uses of CHARMM for highly distributed and cloud resources: MSCALE
and CHARMMing
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 244th National Fall Meeting of the American-Chemical-Society (ACS)
CY AUG 19-23, 2012
CL Philadelphia, PA
SP Amer Chem Soc, Div Hist Chem, Amer Chem Soc
C1 [Miller, Benjamin; Brooks, Bernard] NHLBI, Lab Computat Biol, NIH, Rockville, MD 20892 USA.
[Woodcock, Henry Lee] Univ S Florida, Dept Chem, Tampa, FL 33620 USA.
EM btmiller@nhlbi.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 1
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 19
PY 2012
VL 244
MA 146-COMP
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 220XX
UT WOS:000324621803092
ER
PT J
AU Nadadur, SS
AF Nadadur, Srikanth S.
TI Nanotechnology environmental health and safety: The need for
multidisciplinary consortium apporaches
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 244th National Fall Meeting of the American-Chemical-Society (ACS)
CY AUG 19-23, 2012
CL Philadelphia, PA
SP Amer Chem Soc, Div Hist Chem, Amer Chem Soc
C1 [Nadadur, Srikanth S.] Natl Inst Environm Hlth Sci, Div Extramural Res & Training, Res Triangle Pk, NC 27709 USA.
EM nadadurs@niehs.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 19
PY 2012
VL 244
MA 138-TOXI
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 220XX
UT WOS:000324621808758
ER
PT J
AU Nagy, KJ
Schneider, JP
AF Nagy, Katelyn J.
Schneider, Joel P.
TI Enhanced mechanical rigidity of hydrogels formed from enantiomeric
peptide assemblies
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 244th National Fall Meeting of the American-Chemical-Society (ACS)
CY AUG 19-23, 2012
CL Philadelphia, PA
SP Amer Chem Soc, Div Hist Chem, Amer Chem Soc
C1 [Nagy, Katelyn J.] Univ Delaware, Dept Chem & Biochem, Newark, DE 19716 USA.
[Nagy, Katelyn J.; Schneider, Joel P.] NCI, Biol Chem Lab, Frederick, MD 21701 USA.
EM kjnagy@udel.edu
NR 0
TC 0
Z9 0
U1 1
U2 4
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 19
PY 2012
VL 244
MA 226-POLY
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 220XX
UT WOS:000324621808394
ER
PT J
AU Naumiec, GR
Morse, CL
Shetty, U
Cai, LS
Pike, VW
AF Naumiec, Gregory R.
Morse, Cheryl L.
Shetty, Umesha
Cai, Lisheng
Pike, Victor W.
TI Radiosynthesis of [C-11]CNS 1261, a positron emission tomography
radiotracer for imaging the phencyclidine site of the
N-methyl-D-aspartate receptor
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 244th National Fall Meeting of the American-Chemical-Society (ACS)
CY AUG 19-23, 2012
CL Philadelphia, PA
SP Amer Chem Soc, Div Hist Chem, Amer Chem Soc
C1 [Naumiec, Gregory R.; Morse, Cheryl L.; Shetty, Umesha; Cai, Lisheng; Pike, Victor W.] NIH, Bethesda, MD 20892 USA.
EM naumiecgr@mail.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 19
PY 2012
VL 244
MA 165-MEDI
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 220XX
UT WOS:000324621805789
ER
PT J
AU Nussinov, R
Jang, H
AF Nussinov, Ruth
Jang, Hyunbum
TI Toxic beta-amyloid Alzheimer's ion channels: From structure to function
and design
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 244th National Fall Meeting of the American-Chemical-Society (ACS)
CY AUG 19-23, 2012
CL Philadelphia, PA
SP Amer Chem Soc, Div Hist Chem, Amer Chem Soc
C1 [Nussinov, Ruth; Jang, Hyunbum] NCI, Ctr Canc Res, Nanobiol Program, Frederick, MD 21702 USA.
EM ruthnu@helix.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 1
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 19
PY 2012
VL 244
MA 434-COMP
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 220XX
UT WOS:000324621803350
ER
PT J
AU Nussinov, R
AF Nussinov, Ruth
TI Structural proteome scale prediction of protein-protein interactions
using interfaces
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 244th National Fall Meeting of the American-Chemical-Society (ACS)
CY AUG 19-23, 2012
CL Philadelphia, PA
SP Amer Chem Soc, Div Hist Chem, Amer Chem Soc
C1 [Nussinov, Ruth] NCI Frederick, Ctr Canc Res SAIC, Frederick, MD 21702 USA.
EM ruthnu@helix.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 19
PY 2012
VL 244
MA 103-COMP
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 220XX
UT WOS:000324621803050
ER
PT J
AU Okur, A
Smith, D
Brooks, BR
AF Okur, Asim
Smith, Daniel
Brooks, Bernard R.
TI Using simulation of simulations to evaluate and improve Reservoir
Replica Exchange methods through transition state theory
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 244th National Fall Meeting of the American-Chemical-Society (ACS)
CY AUG 19-23, 2012
CL Philadelphia, PA
SP Amer Chem Soc, Div Hist Chem, Amer Chem Soc
C1 [Okur, Asim; Brooks, Bernard R.] NHLBI, NIH, Bethesda, MD 20892 USA.
[Smith, Daniel] Univ Pittsburgh, Pittsburgh, PA 15260 USA.
EM okura@mail.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 19
PY 2012
VL 244
MA 124-COMP
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 220XX
UT WOS:000324621803070
ER
PT J
AU Opina, AC
Coble, V
Vasalatiy, O
Kobayashi, H
Choyke, PL
Griffiths, GL
AF Opina, Ana Christina
Coble, Vincent
Vasalatiy, Olga
Kobayashi, Hisataka
Choyke, Peter L.
Griffiths, Gary L.
TI Conjugation of Gd(III) complexes to G5 dendrimer as MRI contrast agents
for lymphangiography
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 244th National Fall Meeting of the American-Chemical-Society (ACS)
CY AUG 19-23, 2012
CL Philadelphia, PA
SP Amer Chem Soc, Div Hist Chem, Amer Chem Soc
C1 [Opina, Ana Christina; Coble, Vincent; Vasalatiy, Olga; Griffiths, Gary L.] NIH, Imaging Probe Dev Ctr, Rockville, MD 20850 USA.
[Kobayashi, Hisataka; Choyke, Peter L.] NIH, Mol Imaging Program, Bethesda, MD 20817 USA.
EM opinaal@nhlbi.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 2
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 19
PY 2012
VL 244
MA 219-INOR
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 220XX
UT WOS:000324621805079
ER
PT J
AU Patri, AK
AF Patri, Anil K.
TI Intelligent designs for promising cancer cures: Lessons learned from
preclinical assessment of nanomedicines
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 244th National Fall Meeting of the American-Chemical-Society (ACS)
CY AUG 19-23, 2012
CL Philadelphia, PA
SP Amer Chem Soc, Div Hist Chem, Amer Chem Soc
C1 [Patri, Anil K.] Frederick Natl Lab Canc Res, Nanotechnol Characterizat Lab, Adv Technol Program, SAIC Frederick Inc, Frederick, MD 21702 USA.
EM patria@mail.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 19
PY 2012
VL 244
MA 203-ANYL
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 220XX
UT WOS:000324621801073
ER
PT J
AU Pickard, FC
Miller, BT
Brooks, BR
AF Pickard, Frank C.
Miller, Benjamin T.
Brooks, Bernard R.
TI Thermochemical analysis of two small fast-folding proteins using
coarse-grained simulation
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 244th National Fall Meeting of the American-Chemical-Society (ACS)
CY AUG 19-23, 2012
CL Philadelphia, PA
SP Amer Chem Soc, Div Hist Chem, Amer Chem Soc
C1 [Pickard, Frank C.; Miller, Benjamin T.; Brooks, Bernard R.] NHLBI, Lab Computat Biol, NIH, Bethesda, MD 20892 USA.
EM frank.pickard@nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 19
PY 2012
VL 244
MA 395-COMP
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 220XX
UT WOS:000324621803320
ER
PT J
AU Sathaye, S
Jia, XQ
Schneider, JP
Pochan, DJ
AF Sathaye, Sameer
Jia, Xinqiao
Schneider, Joel P.
Pochan, Darrin J.
TI Hybrid networks from hyaluronic acid and hierarchically self-assembled
b-sheet peptide networks
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 244th National Fall Meeting of the American-Chemical-Society (ACS)
CY AUG 19-23, 2012
CL Philadelphia, PA
SP Amer Chem Soc, Div Hist Chem, Amer Chem Soc
C1 [Sathaye, Sameer; Jia, Xinqiao; Pochan, Darrin J.] Univ Delaware, Dept Mat Sci & Engn, Newark, DE 19716 USA.
[Schneider, Joel P.] NCI, Biol Chem Lab, Frederick, MD 21702 USA.
EM sameers@udel.edu
NR 0
TC 0
Z9 0
U1 1
U2 2
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 19
PY 2012
VL 244
MA 221-POLY
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 220XX
UT WOS:000324621808390
ER
PT J
AU Smith, DJ
Yap, GPA
Kelley, JA
Schneider, JP
AF Smith, Daniel J.
Yap, Glenn P. A.
Kelley, James A.
Schneider, Joel P.
TI Enhanced stereoselectivity of a Cu(II) complex chiral auxiliary in the
synthesis of Fmoc-L-g-carboxyglutamic acid
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 244th National Fall Meeting of the American-Chemical-Society (ACS)
CY AUG 19-23, 2012
CL Philadelphia, PA
SP Amer Chem Soc, Div Hist Chem, Amer Chem Soc
C1 [Smith, Daniel J.; Kelley, James A.; Schneider, Joel P.] Frederick Natl Lab Canc Res, Biol Chem Lab, Frederick, MD 21702 USA.
[Smith, Daniel J.; Yap, Glenn P. A.] Univ Delaware, Dept Chem & Biochem, Newark, DE 19716 USA.
EM smithdj@mail.nih.gov
NR 0
TC 0
Z9 0
U1 1
U2 2
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 19
PY 2012
VL 244
MA 227-POLY
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 220XX
UT WOS:000324621808395
ER
PT J
AU Sonmez, C
Schneider, JP
AF Sonmez, Cem
Schneider, Joel P.
TI Bacterial expression of a self-assembling peptide hydrogelator
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 244th National Fall Meeting of the American-Chemical-Society (ACS)
CY AUG 19-23, 2012
CL Philadelphia, PA
SP Amer Chem Soc, Div Hist Chem, Amer Chem Soc
C1 [Sonmez, Cem; Schneider, Joel P.] NCI, Biol Chem Lab, Frederick, MD 21702 USA.
[Sonmez, Cem] Univ Delaware, Dept Chem & Biochem, Newark, DE 19716 USA.
EM cem.sonmez@nih.gov
RI Sonmez, Cem/C-2730-2015
OI Sonmez, Cem/0000-0002-6071-641X
NR 0
TC 0
Z9 0
U1 0
U2 1
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 19
PY 2012
VL 244
MA 223-POLY
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 220XX
UT WOS:000324621808392
ER
PT J
AU Sun, HM
Sakamuru, S
Xia, MH
Austin, CP
Huang, RL
AF Sun, Hongmao
Sakamuru, Srilatha
Xia, Menghang
Austin, Christopher P.
Huang, Ruili
TI Genetic algorithm guided optimization of pharmacophore models for
estrogen receptor agonists
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 244th National Fall Meeting of the American-Chemical-Society (ACS)
CY AUG 19-23, 2012
CL Philadelphia, PA
SP Amer Chem Soc, Div Hist Chem, Amer Chem Soc
C1 [Sun, Hongmao; Sakamuru, Srilatha; Xia, Menghang; Austin, Christopher P.; Huang, Ruili] NIH, NCATS, Rockville, MD 20850 USA.
EM hongmao.sun@nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 19
PY 2012
VL 244
MA 233-COMP
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 220XX
UT WOS:000324621803175
ER
PT J
AU Tan, ML
Cendagorta, JR
Ichiye, T
AF Tan, Mingliang
Cendagorta, Joseph R.
Ichiye, Toshiko
TI Solvation of amphiphilic molecules by SSDQO water
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 244th National Fall Meeting of the American-Chemical-Society (ACS)
CY AUG 19-23, 2012
CL Philadelphia, PA
SP Amer Chem Soc, Div Hist Chem, Amer Chem Soc
C1 [Tan, Mingliang; Cendagorta, Joseph R.; Ichiye, Toshiko] Georgetown Univ, Dept Chem, Washington, DC 20057 USA.
[Ichiye, Toshiko] NHBI, Lab Computat Biol, NIH, Bethesda, MD 20892 USA.
EM ti9@georgetown.edu
NR 0
TC 0
Z9 0
U1 0
U2 1
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 19
PY 2012
VL 244
MA 277-COMP
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 220XX
UT WOS:000324621803217
ER
PT J
AU Tan, ML
Ichiye, T
AF Tan, Mingliang
Ichiye, Toshiko
TI Soft-sticky dipole-quadrupole-octopole model of liquid water
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 244th National Fall Meeting of the American-Chemical-Society (ACS)
CY AUG 19-23, 2012
CL Philadelphia, PA
SP Amer Chem Soc, Div Hist Chem, Amer Chem Soc
C1 [Tan, Mingliang; Ichiye, Toshiko] Georgetown Univ, Dept Chem, Wa, DC 20057 USA.
[Ichiye, Toshiko] NHBI, NIH, Bethesda, MD 20892 USA.
EM ti9@georgetown.edu
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 19
PY 2012
VL 244
MA 99-COMP
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 220XX
UT WOS:000324621803046
ER
PT J
AU Tao, P
Brooks, BR
AF Tao, Peng
Brooks, Bernard R.
TI Free energy profile along reference reaction path through rigid
structure dynamics
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 244th National Fall Meeting of the American-Chemical-Society (ACS)
CY AUG 19-23, 2012
CL Philadelphia, PA
SP Amer Chem Soc, Div Hist Chem, Amer Chem Soc
C1 [Tao, Peng; Brooks, Bernard R.] NHLBI, Lab Computat Biol, NIH, Bethesda, MD 20892 USA.
EM peng.tao@nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 19
PY 2012
VL 244
MA 171-COMP
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 220XX
UT WOS:000324621803116
ER
PT J
AU Tsai, DH
Elzey, S
DelRio, FW
Keene, AM
Tyner, KM
Clogston, JD
MacCuspie, RI
Guha, S
Zachariah, MR
Hackley, VA
AF Tsai, De-Hao
Elzey, Sherrie
DelRio, Frank W.
Keene, Athena M.
Tyner, Katherine M.
Clogston, Jeffrey D.
MacCuspie, Robert I.
Guha, Suvajyoti
Zachariah, Michael R.
Hackley, Vincent A.
TI Tumor necrosis factor interaction with gold nanoparticles
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 244th National Fall Meeting of the American-Chemical-Society (ACS)
CY AUG 19-23, 2012
CL Philadelphia, PA
SP Amer Chem Soc, Div Hist Chem, Amer Chem Soc
C1 [Tsai, De-Hao; Elzey, Sherrie; DelRio, Frank W.; MacCuspie, Robert I.; Guha, Suvajyoti; Zachariah, Michael R.; Hackley, Vincent A.] NIST, Mat Measurement Lab, Gaithersburg, MD 20899 USA.
[Keene, Athena M.; Tyner, Katherine M.] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA.
[Clogston, Jeffrey D.] NCI Frederick, Nanotechnol Characterizat Lab, SAIC Frederick Inc, Frederick, MD 21702 USA.
[Guha, Suvajyoti; Zachariah, Michael R.] Univ Maryland, Dept Mech Engn, College Pk, MD 20742 USA.
[Guha, Suvajyoti; Zachariah, Michael R.] Univ Maryland, Dept Chem, College Pk, MD 20742 USA.
EM dhtsai@nist.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 19
PY 2012
VL 244
MA 493-COLL
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 220XX
UT WOS:000324621802673
ER
PT J
AU Weidlich, IE
Filippov, IV
Thorpe, I
AF Weidlich, Iwona E.
Filippov, Igor V.
Thorpe, Ian
TI Improving drug development by connecting medicinal chemistry with drug
repositioning and modern machine learning methods
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 244th National Fall Meeting of the American-Chemical-Society (ACS)
CY AUG 19-23, 2012
CL Philadelphia, PA
SP Amer Chem Soc, Div Hist Chem, Amer Chem Soc
C1 [Weidlich, Iwona E.; Thorpe, Ian] Univ Maryland Baltimore Cty, Dept Chem & Biochem, Baltimore, MD 21250 USA.
[Filippov, Igor V.] NIH, Biol Chem Lab, Basic Sci Program, SAIC Frederick Inc,Frederick Natl Lab, Frederick, MD 21702 USA.
EM iweidlic@umbc.edu
NR 0
TC 0
Z9 0
U1 0
U2 2
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 19
PY 2012
VL 244
MA 22-CINF
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 220XX
UT WOS:000324621802105
ER
PT J
AU Yang, W
AF Yang, Wei
TI Structural basis of human DNA polymerase h-mediated chemoresistance to
Cisplatin
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 244th National Fall Meeting of the American-Chemical-Society (ACS)
CY AUG 19-23, 2012
CL Philadelphia, PA
SP Amer Chem Soc, Div Hist Chem, Amer Chem Soc
C1 [Yang, Wei] NIDDK, LMB, NIH, Bethesda, MD 20892 USA.
EM wei.yang@nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 19
PY 2012
VL 244
MA 36-TOXI
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 220XX
UT WOS:000324621808657
ER
PT J
AU Zakharov, AV
Peach, ML
Sitzmann, M
Filippov, IV
Nicklaus, MC
AF Zakharov, Alexey V.
Peach, Megan L.
Sitzmann, Markus
Filippov, Igor V.
Nicklaus, Marc C.
TI QSAR modeling of human liver microsomal stability
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 244th National Fall Meeting of the American-Chemical-Society (ACS)
CY AUG 19-23, 2012
CL Philadelphia, PA
SP Amer Chem Soc, Div Hist Chem, Amer Chem Soc
C1 [Zakharov, Alexey V.; Sitzmann, Markus; Nicklaus, Marc C.] NCI, Biol Chem Lab, NIH, DHHS, Frederick, MD 21702 USA.
[Peach, Megan L.; Filippov, Igor V.] SAIC Frederick Inc, Biol Chem Lab, Basic Sci Program, Frederick, MD 21702 USA.
EM alexey.zakharov@nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 19
PY 2012
VL 244
MA 81-COMP
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 220XX
UT WOS:000324621803030
ER
PT J
AU Zhao, C
Micklitsch, CM
Oquare, BY
Appella, DH
AF Zhao, Chao
Micklitsch, Christopher M.
Oquare, Bereket Y.
Appella, Daniel H.
TI Rational design of functional peptide nucleic acids for the direct and
ultra high sensitive detection of HIV-1 DNA and RNA with a
sandwich-hybridization assay
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 244th National Fall Meeting of the American-Chemical-Society (ACS)
CY AUG 19-23, 2012
CL Philadelphia, PA
SP Amer Chem Soc, Div Hist Chem, Amer Chem Soc
C1 [Zhao, Chao; Micklitsch, Christopher M.; Oquare, Bereket Y.; Appella, Daniel H.] NIDDK, NIH, Bethesda, MD 20892 USA.
EM chao.zhao@nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 2
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 19
PY 2012
VL 244
MA 180-MEDI
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 220XX
UT WOS:000324621805802
ER
PT J
AU Zhao, XZ
Maddali, K
Smith, SJ
Metifiot, M
Hare, S
Cherepanov, P
Hughes, SH
Pommier, Y
Burke, TR
AF Zhao, Xue Zhi
Maddali, Kasthuraiah
Smith, Steven J.
Metifiot, Mathieu
Hare, Stephen
Cherepanov, Peter
Hughes, Stephen H.
Pommier, Yves
Burke, Terrence R., Jr.
TI Hydroxy-pyrrolopyridine-trione based HIV-1 integrase inhibitors
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 244th National Fall Meeting of the American-Chemical-Society (ACS)
CY AUG 19-23, 2012
CL Philadelphia, PA
SP Amer Chem Soc, Div Hist Chem, Amer Chem Soc
C1 [Zhao, Xue Zhi; Burke, Terrence R., Jr.] NCI, Frederick Natl Lab Canc Res, NIH, Biol Chem Lab, Frederick, MD 21702 USA.
[Maddali, Kasthuraiah; Metifiot, Mathieu; Pommier, Yves] NCI, Ctr Canc Res, NIH, Mol Pharmacol Lab, Bethesda, MD 20892 USA.
[Smith, Steven J.; Hughes, Stephen H.] NCI, Frederick Natl Lab Canc Res, NIH, HIV Drug Resistance Program, Frederick, MD 21702 USA.
[Hare, Stephen; Cherepanov, Peter] Univ London Imperial Coll Sci Technol & Med, Div Infect Dis, London W2 1PG, England.
EM zhaoxue@mail.nih.gov
NR 0
TC 0
Z9 0
U1 1
U2 4
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 19
PY 2012
VL 244
MA 141-MEDI
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 220XX
UT WOS:000324621805765
ER
PT J
AU Zhou, ZL
Yu, PP
Geller, H
Ober, C
AF Zhou, Zhaoli
Yu, Panpan
Geller, Herbert
Ober, Christopher
TI Biomaterials with tethered acetylcholine functionalities for neuronal
cell culture and patterning
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 244th National Fall Meeting of the American-Chemical-Society (ACS)
CY AUG 19-23, 2012
CL Philadelphia, PA
SP Amer Chem Soc, Div Hist Chem, Amer Chem Soc
C1 [Zhou, Zhaoli] Cornell Univ, Dept Chem & Chem Biol, Ithaca, NY 14853 USA.
[Ober, Christopher] Cornell Univ, Dept Mat Sci & Engn, Ithaca, NY 14853 USA.
[Yu, Panpan; Geller, Herbert] NHLBI, Dev Neurobiol Sect, Div Intramural Res, NIH, Bethesda, MD 20892 USA.
EM zz56@cornell.edu
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 19
PY 2012
VL 244
MA 307-PMSE
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 220XX
UT WOS:000324621808067
ER
PT J
AU Carver, FW
Elvevag, B
Altamura, M
Weinberger, DR
Coppola, R
AF Carver, Frederick W.
Elvevag, Brita
Altamura, Mario
Weinberger, Daniel R.
Coppola, Richard
TI The Neuromagnetic Dynamics of Time Perception
SO PLOS ONE
LA English
DT Article
ID TRANSCRANIAL MAGNETIC STIMULATION; SUPPLEMENTARY MOTOR AREA; PREFRONTAL
CORTEX; BRAIN ACTIVATION; BASAL GANGLIA; FMRI; MEMORY; CLOCK;
DISCRIMINATION; SCHIZOPHRENIA
AB Examining real-time cortical dynamics is crucial for understanding time perception. Using magnetoencephalography we studied auditory duration discrimination of short (<.5 s) versus long tones (>.5 s) versus a pitch control. Time-frequency analysis of event-related fields showed widespread beta-band (13-30 Hz) desynchronization during all tone presentations. Synthetic aperture magnetometry indicated automatic primarily sensorimotor responses in short and pitch conditions, with activation specific to timing in bilateral inferior frontal gyrus. In the long condition, a right lateralized network was active, including lateral prefrontal cortices, inferior frontal gyrus, supramarginal gyrus and secondary auditory areas. Activation in this network peaked just after attention to tone duration was no longer necessary, suggesting a role in sustaining representation of the interval. These data expand our understanding of time perception by revealing its complex cortical spatiotemporal signature.
C1 [Carver, Frederick W.; Coppola, Richard] NIMH, MEG Core Facil, Bethesda, MD 20892 USA.
[Elvevag, Brita; Altamura, Mario; Weinberger, Daniel R.; Coppola, Richard] NIMH, Clin Brain Disorders Branch, Bethesda, MD 20892 USA.
RP Carver, FW (reprint author), NIMH, MEG Core Facil, Bethesda, MD 20892 USA.
EM brita@elvevaag.net
FU National Institute of Mental Health, National Institutes of Health
FX This research was supported by the Intramural Research Program of the
National Institute of Mental Health, National Institutes of Health:
http://intramural.nimh.nih.gov/. The funders had no role in study
design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 55
TC 2
Z9 2
U1 1
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 17
PY 2012
VL 7
IS 8
AR e42618
DI 10.1371/journal.pone.0042618
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 996DG
UT WOS:000308063700016
PM 22912714
ER
PT J
AU Pripuzova, N
Wang, R
Tsai, S
Li, BJ
Hung, GC
Ptak, RG
Lo, SC
AF Pripuzova, Natalia
Wang, Richard
Tsai, Shien
Li, Bingjie
Hung, Guo-Chiuan
Ptak, Roger G.
Lo, Shyh-Ching
TI Development of Real-Time PCR Array for Simultaneous Detection of Eight
Human Blood-Borne Viral Pathogens
SO PLOS ONE
LA English
DT Article
ID DISEASES (RAPID)-BIOACTIVE AMPLIFICATION; RELIABLE ASSAY PROTOCOL;
B-VIRUS DNA; WEST-NILE-VIRUS; RAPID DETECTION; PROBING BAP; HIV TYPE-1;
GROUP-O; IDENTIFICATION; QUANTIFICATION
AB Background: Real-time PCR array for rapid detection of multiple viral pathogens should be highly useful in cases where the sample volume and the time of testing are limited, i.e. in the eligibility testing of tissue and organ donors.
Findings: We developed a real-time PCR array capable of simultaneously detecting eight human viral pathogens: human immunodeficiency virus types 1 and 2 (HIV-1 and -2), hepatitis B virus (HBV), hepatitis C virus (HCV), human T-cell leukemia virus-1 and -2 (HTLV-1 and -2), vaccinia virus (VACV) and West Nile virus (WNV). One hundred twenty (120) primers were designed using a combination of bioinformatics approaches, and, after experimental testing, 24 primer sets targeting eight viral pathogens were selected to set up the array with SYBR Green chemistry. The specificity and sensitivity of the virus-specific primer sets selected for the array were evaluated using analytical panels with known amounts of viruses spiked into human plasma. The array detected: 10 genome equivalents (geq)/ml of HIV-2 and HCV, 50 geq of HIV-1 (subtype B), HBV (genotype A) and WNV. It detected 100-1,000 geq/ml of plasma of HIV-1 subtypes (A - G), group N and CRF (AE and AG) isolates. Further evaluation with a panel consisting of 28 HIV-1 and HIV-2 clinical isolates revealed no cross-reactivity of HIV-1 or HIV-2 specific primers with another type of HIV. All 28 viral isolates were identified with specific primer sets targeting the most conserved genome areas. The PCR array correctly identified viral infections in a panel of 17 previously quantified clinical plasma samples positive for HIV-1, HCV or HBV at as low as several geq per PCR reaction.
Conclusions: The viral array described here demonstrated adequate performance in the testing of donors' clinical samples. Further improvement in its sensitivity for the broad spectrum of HIV-1 subtypes is under development.
C1 [Pripuzova, Natalia; Tsai, Shien; Li, Bingjie; Hung, Guo-Chiuan; Lo, Shyh-Ching] US FDA, Tissue Microbiol Lab, Div Cellular & Gene Therapies, Off Cellular Tissue & Gene Therapy,Ctr Biol Evalu, Bethesda, MD 20014 USA.
[Wang, Richard] NIH, Dept Transfus Med, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA.
[Ptak, Roger G.] So Res Inst, Dept Infect Dis Res, Frederick, MD USA.
RP Pripuzova, N (reprint author), US FDA, Tissue Microbiol Lab, Div Cellular & Gene Therapies, Off Cellular Tissue & Gene Therapy,Ctr Biol Evalu, Bethesda, MD 20014 USA.
EM ShyhChing.Lo@fda.hhs.gov
NR 43
TC 5
Z9 5
U1 1
U2 4
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD AUG 17
PY 2012
VL 7
IS 8
AR e43246
DI 10.1371/journal.pone.0043246
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 996DG
UT WOS:000308063700066
PM 22912836
ER
PT J
AU Vargas, M
Karamsetty, R
Leppla, SH
Chaudry, GJ
AF Vargas, Micaela
Karamsetty, Raghavendra
Leppla, Stephen H.
Chaudry, G. Jilani
TI Broad Expression Analysis of Human ANTXR1/TEM8 Transcripts Reveals
Differential Expression and Novel Splizce Variants
SO PLOS ONE
LA English
DT Article
ID ANTHRAX LETHAL FACTOR; PROTEIN-KINASE KINASE; PROTECTIVE ANTIGEN; TOXIN
RECEPTOR; CAPILLARY MORPHOGENESIS; TUMOR ENDOTHELIUM; DEPENDENT PROCESS;
EUKARYOTIC CELLS; MAMMALIAN-CELLS; FACTOR CLEAVES
AB Tumor endothelial marker 8 (TEM8; ANTXR1) is one of two anthrax toxin receptors; the other is capillary morphogenesis gene 2 protein (CMG2; ANTXR2). TEM8 shows enhanced expression in certain tumor endothelia, and is thought to be a player in tumor vasculature formation. However, a comprehensive expression profile of individual TEM8 variants in normal or cancerous tissues is lacking. In this work we carried out an extensive analysis of all splice variants of human TEM8 in 12 digestive tissues, and 8 each fetal and adult tissues, 6 of them cognate pairs. Using variant-specific primers, we first ascertained the status of full-length transcripts by nested PCR. We then carried out quantitative analysis of each transcript by real-time PCR. Three splice variants of TEM8 were reported before, two single-pass integral membrane forms (V1 and V2) and one secreted (V3). Our analysis has revealed two new variants, one encoding a membrane-bound form of the receptor and the other secreted, which we have designated V4 and V5, respectively. All tissues had V1, V2, V3, and V4, but only prostate had V5. Real-time PCR revealed that all variants are present at different levels in various tissues. V3 appeared the most abundant of all. To ascertain its functionality for anthrax toxin, we expressed the newly identified form V4 in a receptor-negative host cell, and included V1 and V2 for comparison. Cytotoxicity, toxin binding, and internalization assays showed V4 to be as efficient a receptor as V1 and V2.
C1 [Vargas, Micaela; Karamsetty, Raghavendra; Chaudry, G. Jilani] Univ Texas San Antonio, Dept Biol, Cell & Mol Biol Program, San Antonio, TX USA.
[Leppla, Stephen H.] NIAID, Microbial Pathogenesis Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Vargas, M (reprint author), Univ Illinois, Coll Med, Dept Pharmacol, Chicago, IL 60680 USA.
EM jilani.chaudry@utsa.edu
FU University of Texas at San Antonio; San Antonio Area Foundation;
National Institute of Allergy and Infectious Diseases/National Institute
of General Medical Sciences [SC1AI081654]; Minority Biomedical Research
Support-Research Initiative for Scientific Enhancement [GM60655]
FX Funding for this work was provided to GJC by The University of Texas at
San Antonio, San Antonio Area Foundation, and National Institute of
Allergy and Infectious Diseases/National Institute of General Medical
Sciences grant SC1AI081654 (Minority Biomedical Research Support-Support
of Competitive Research). MV was supported for her PhD by the Minority
Biomedical Research Support-Research Initiative for Scientific
Enhancement grant GM60655 to the University of Texas at San Antonio. The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 46
TC 5
Z9 7
U1 1
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 17
PY 2012
VL 7
IS 8
AR e43174
DI 10.1371/journal.pone.0043174
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 996DG
UT WOS:000308063700055
PM 22912819
ER
PT J
AU Cui, HT
Thomas, JD
Burke, TR
Rader, C
AF Cui, Huiting
Thomas, Joshua D.
Burke, Terrence R., Jr.
Rader, Christoph
TI Chemically Programmed Bispecific Antibodies That Recruit and Activate T
Cells
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID CANCER-THERAPY; ENGAGING ANTIBODY; TUMOR-CELLS; LYSIS; IMMUNOTHERAPY;
THERAPEUTICS; GENERATION; RECEPTORS; INTEGRIN; BINDING
AB Bispecific antibodies (biAbs) that mediate cytotoxicity by recruiting and activating endogenous immune cells are an emerging class of next-generation antibody therapeutics. Of particular interest are biAbs of relatively small size (similar to 50 kDa) that can redirect cytotoxic T cells through simultaneous binding of tumor cells. Here we describe a conceptually unique class of biAbs in which the tumor cell specificity of a humanized antibody fragment that recognizes CD3 on T cells is chemically programmed through a C-terminal selenocysteine (Sec) residue. We demonstrate that through chemically programmed specificity for integrin alpha(4)beta(1) or folate receptor 1 (FOLR1), and common specificity for CD3, these hybrid molecules exert potent and specific in vitro and ex vivo cytotoxicity toward tumor cell lines and primary tumor cells in the presence of primary T cells. Importantly, the generic nature of chemical programming allows one to apply our approach to virtually any specificity, promising a broad utility of chemically programmed biAbs in cancer therapy.
C1 [Cui, Huiting; Rader, Christoph] NCI, Expt Transplantat & Immunol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Thomas, Joshua D.; Burke, Terrence R., Jr.] NCI, Biol Chem Lab, Frederick Natl Lab Canc Res, Ctr Canc Res,NIH, Frederick, MD 21702 USA.
RP Rader, C (reprint author), Scripps Florida, Scripps Res Inst, Dept Canc Biol, 130 Scripps Way 2C1, Jupiter, FL 33458 USA.
EM crader@scripps.edu
RI Burke, Terrence/N-2601-2014
FU Center for Cancer Research, National Cancer Institute, National
Institutes of Health
FX This work was supported, in whole or in part, by the intramural research
program of the Center for Cancer Research, National Cancer Institute,
National Institutes of Health.
NR 33
TC 11
Z9 11
U1 0
U2 23
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD AUG 17
PY 2012
VL 287
IS 34
BP 28206
EP 28214
DI 10.1074/jbc.M112.384594
PG 9
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 996HD
UT WOS:000308074600001
PM 22761439
ER
PT J
AU Doyle, SM
Hoskins, JR
Wickner, S
AF Doyle, Shannon M.
Hoskins, Joel R.
Wickner, Sue
TI DnaK Chaperone-dependent Disaggregation by Caseinolytic Peptidase B
(ClpB) Mutants Reveals Functional Overlap in the N-terminal Domain and
Nucleotide-binding Domain-1 Pore Tyrosine
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID ESCHERICHIA-COLI; PROTEIN DISAGGREGATION; SUBSTRATE RECOGNITION;
AGGREGATED PROTEINS; ATP HYDROLYSIS; AAA; HSP104; THERMOTOLERANCE;
ATPASES; HSP70
AB Protein disaggregation in Escherichia coli is carried out by ClpB, an AAA(+) (ATPases associated with various cellular activities) molecular chaperone, together with the DnaK chaperone system. Conformational changes in ClpB driven by ATP binding and hydrolysis promote substrate binding, unfolding, and translocation. Conserved pore tyrosines in both nucleotide-binding domain-1 (NBD-1) and -2 (NBD-2), which reside in flexible loops extending into the central pore of the ClpB hexamer, bind substrates. When the NBD-1 pore loop tyrosine is substituted with alanine (Y251A), ClpB can collaborate with the DnaK system in disaggregation, although activity is reduced. The N-domain has also been implicated in substrate binding, and like the NBD-1 pore loop tyrosine, it is not essential for disaggregation activity. To further probe the function and interplay of the ClpB N-domain and the NBD-1 pore loop, we made a double mutant with an N-domain deletion and a Y251A substitution. This ClpB double mutant is inactive in substrate disaggregation with the DnaK system, although each single mutant alone can function with DnaK. Our data suggest that this loss in activity is primarily due to a decrease in substrate engagement by ClpB prior to substrate unfolding and translocation and indicate an overlapping function for the N-domain and NBD-1 pore tyrosine. Furthermore, the functional overlap seen in the presence of the DnaK system is not observed in the absence of DnaK. For innate ClpB unfolding activity, the NBD-1 pore tyrosine is required, and the presence of the N-domain is insufficient to overcome the defect of the ClpB Y251A mutant.
C1 [Doyle, Shannon M.; Hoskins, Joel R.; Wickner, Sue] NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Wickner, S (reprint author), NCI, Mol Biol Lab, NIH, 37 Convent Dr,Bldg 37,Rm 5144, Bethesda, MD 20892 USA.
EM wickners@mail.nih.gov
FU National Institutes of Health Intramural Research Program, NCI, Center
for Cancer Research
FX This work was supported, in whole or in part, by National Institutes of
Health Intramural Research Program, NCI, Center for Cancer Research.
NR 45
TC 9
Z9 9
U1 2
U2 3
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD AUG 17
PY 2012
VL 287
IS 34
BP 28470
EP 28479
DI 10.1074/jbc.M112.383091
PG 10
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 996HD
UT WOS:000308074600022
PM 22745126
ER
PT J
AU Ramakrishnan, B
Boeggeman, E
Qasba, PK
AF Ramakrishnan, Boopathy
Boeggeman, Elizabeth
Qasba, Pradman K.
TI Binding of N-Acetylglucosamine (GlcNAc) beta 1-6-branched
Oligosaccharide Acceptors to beta 4-Galactosyltransferase I Reveals a
New Ligand Binding Mode
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID ALPHA-LACTALBUMIN; CRYSTAL-STRUCTURE; LACTOSE SYNTHETASE;
GALACTOSYLTRANSFERASE; BETA-1,4-GALACTOSYLTRANSFERASE-I; COMPLEX;
MUTANT; IDENTIFICATION; SPECIFICITY; METASTASIS
AB N-Acetyllactosamine is the most prevalent disaccharide moiety in the glycans on the surface of mammalian cells and often found as repeat units in the linear and branched polylactosamines, known as i- and I-antigen, respectively. The beta 1-4-galactosyltransferase- I (beta 4Gal-T1) enzyme is responsible for the synthesis of the N-acetyllactosamine moiety. To understand its oligosaccharide acceptor specificity, we have previously investigated the binding of tri- and pentasaccharides of N-glycan with a GlcNAc at their nonreducing end and found that the extended sugar moiety in these acceptor substrates binds to the crevice present at the acceptor substrate binding site of the beta 4Gal-T1 molecule. Here we report seven crystal structures of beta 4Gal-T1 in complex with an oligosaccharide acceptor with a nonreducing end GlcNAc that has a beta 1-6-glycosidic link and that are analogous to either N-glycan or i/I-antigen. In the crystal structure of the complex of beta 4Gal-T1 with I-antigen analog pentasaccharide, the beta 1-6-branched GlcNAc moiety is bound to the sugar acceptor binding site of the beta 4Gal-T1 molecule in a way similar to the crystal structures described previously; however, the extended linear tetrasaccharide moiety does not interact with the previously found extended sugar binding site on the beta 4Gal-T1 molecule. Instead, it interacts with the different hydrophobic surface of the protein molecule formed by the residues Tyr-276, Trp-310, and Phe-356. Results from the present and previous studies suggest that beta 4Gal-T1 molecule has two different oligosaccharide binding regions for the binding of the extended oligosaccharide moiety of the acceptor substrate.
C1 [Ramakrishnan, Boopathy; Boeggeman, Elizabeth; Qasba, Pradman K.] NIH, Struct Glycobiol Sect, SAIC Frederick Inc,Ctr Canc Res Nanobiol Program, Ctr Canc Res,Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
[Ramakrishnan, Boopathy; Boeggeman, Elizabeth] NIH, Basic Sci Program, SAIC Frederick Inc,Ctr Canc Res Nanobiol Program, Ctr Canc Res,Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
RP Qasba, PK (reprint author), Frederick Natl Lab, Struct Glycobiol Sect, CCRNP, CCR, Bldg 469,Rm 221, Frederick, MD 21702 USA.
EM qasba@helix.nih.gov
FU National Institutes of Health through the NCI [HHSN261200800001E];
National Institutes of Health, Frederick National Laboratory for Cancer
Research
FX This work was supported, in whole or in part, by National Institutes of
Health Contract HHSN261200800001E through the NCI. This research was
supported (in part) by the Intramural Research Program of the National
Institutes of Health, Frederick National Laboratory for Cancer Research.
NR 35
TC 3
Z9 3
U1 0
U2 4
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD AUG 17
PY 2012
VL 287
IS 34
BP 28666
EP 28674
DI 10.1074/jbc.M112.373514
PG 9
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 996HD
UT WOS:000308074600040
PM 22740701
ER
PT J
AU Colaianni, G
Sun, L
Di Benedetto, A
Tamma, R
Zhu, LL
Cao, J
Grano, M
Yuen, T
Colucci, S
Cuscito, C
Mancini, L
Li, JH
Nishimori, K
Bab, I
Lee, HJ
Iqbal, J
Young, WS
Rosen, C
Zallone, A
Zaidi, M
AF Colaianni, Graziana
Sun, Li
Di Benedetto, Adriana
Tamma, Roberto
Zhu, Ling-Ling
Cao, Jay
Grano, Maria
Yuen, Tony
Colucci, Sylvia
Cuscito, Concetta
Mancini, Lucia
Li, Jianhua
Nishimori, Katsuhiko
Bab, Itai
Lee, Heon-Jin
Iqbal, Jameel
Young, W. Scott, III
Rosen, Clifford
Zallone, Alberta
Zaidi, Mone
TI Bone Marrow Oxytocin Mediates the Anabolic Action of Estrogen on the
Skeleton
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID RECEPTOR; EXPRESSION; HORMONE; MICE; LACTATION; GENE; DIFFERENTIATION;
PARTURITION; CELLS; ACTH
AB Estrogen uses two mechanisms to exert its effect on the skeleton: it inhibits bone resorption by osteoclasts and, at higher doses, can stimulate bone formation. Although the antiresorptive action of estrogen arises from the inhibition of the MAPK JNK, the mechanism of its effect on the osteoblast remains unclear. Here, we report that the anabolic action of estrogen in mice occurs, at least in part, through oxytocin (OT) produced by osteoblasts in bone marrow. We show that the absence of OT receptors (OTRs) in OTR-/- osteoblasts or attenuation of OTR expression in silenced cells inhibits estrogen-induced osteoblast differentiation, transcription factor up-regulation, and/or OT production in vitro. In vivo, OTR-/- mice, known to have a bone formation defect, fail to display increases in trabecular bone volume, cortical thickness, and bone formation in response to estrogen. Furthermore, osteoblast-specific Col2.3-Cre(+)/OTRfl/fl mice, but not TRAP-Cre(+)/OTRfl/fl mice, mimic the OTR-/- phenotype and also fail to respond to estrogen. These data attribute the phenotype of OTR deficiency to an osteoblastic rather than an osteoclastic defect. Physiologically, feed-forward OT release in bone marrow by a rising estrogen concentration may facilitate rapid skeletal recovery during the latter phases of lactation.
C1 [Colaianni, Graziana; Di Benedetto, Adriana; Tamma, Roberto; Grano, Maria; Colucci, Sylvia; Cuscito, Concetta; Mancini, Lucia; Zallone, Alberta] Univ Bari, Sch Med, Dept Human Anat & Histol, I-70124 Bari, Italy.
[Colaianni, Graziana; Sun, Li; Zhu, Ling-Ling; Yuen, Tony; Li, Jianhua; Iqbal, Jameel; Zaidi, Mone] Mt Sinai Sch Med, Mt Sinai Bone Program, New York, NY 10029 USA.
[Cao, Jay] Grand Forks Human Nutr Res Ctr, ARS, USDA, Grand Forks, ND 58201 USA.
[Nishimori, Katsuhiko] Tohoku Univ, Grad Sch Agr Sci, Aoba Ku, Sendai, Miyagi 9818555, Japan.
[Bab, Itai] Hebrew Univ Jerusalem, Bone Lab, IL-91120 Jerusalem, Israel.
[Lee, Heon-Jin] Kyungpook Natl Univ, Dept Oral Microbiol, Sch Dent, Taegu 702701, South Korea.
[Young, W. Scott, III] NIMH, Sect Neural Gene Express, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Rosen, Clifford] Maine Med Ctr, Res Inst, Scarborough, ME 04074 USA.
RP Zallone, A (reprint author), Univ Bari, Sch Med, Dept Human Anat & Histol, I-70124 Bari, Italy.
EM alberta.zallone@fastwebnet.it; mone.zaidi@mssm.edu
RI Young, W Scott/A-9333-2009; tamma, roberto/C-3679-2016;
OI , Heon-Jin/0000-0002-1911-5014; Young, W Scott/0000-0001-6614-5112;
Colaianni, Graziana/0000-0001-8501-5399; Grano,
Maria/0000-0002-7121-5899
FU National Institutes of Health from NIA [AG023176, AG040132]; NIDDK
[DK080459]; National Institute of Mental Health [Z01-MH-002498-23];
Italian Space Agency; European Space Agency; Ministero dell'Istruzione,
dell'Universita della Ricerca; United States Department of Agriculture
Agricultural Research Service [5450-51000-046-00D]; American Federation
for Aging Research
FX This work was supported, in whole or in part, by National Institutes of
Health Grants AG023176 and AG040132 from NIA (to M. Z.) and DK080459
from NIDDK (to M. Z. and L. S.) and by National Institute of Mental
Health Intramural Research Program Grant Z01-MH-002498-23 (to H.-J. L.
and W. S. Y.). This work was also supported by grants from the Italian
Space Agency (Osteoporosis and Muscular Atrophy Project), the European
Space Agency (European Research in Space and Terrestrial Osteoporosis
Microgravity Application Promotion Project), and the Ministero
dell'Istruzione, dell'Universita della Ricerca (to A. Z.); by United
States Department of Agriculture Agricultural Research Service Current
Research Information System Program Grant 5450-51000-046-00D (to J. C.);
and by the American Federation for Aging Research (to J. I.).
NR 33
TC 26
Z9 28
U1 1
U2 6
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD AUG 17
PY 2012
VL 287
IS 34
BP 29159
EP 29167
DI 10.1074/jbc.M112.365049
PG 9
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 996HD
UT WOS:000308074600081
PM 22761429
ER
PT J
AU Boonnak, K
Paskel, M
Matsuoka, Y
Vogel, L
Subbarao, K
AF Boonnak, Kobporn
Paskel, Myeisha
Matsuoka, Yumiko
Vogel, Leatrice
Subbarao, Kanta
TI Evaluation of replication, immunogenicity and protective efficacy of a
live attenuated cold-adapted pandemic H1N1 influenza virus vaccine in
non-human primates
SO VACCINE
LA English
DT Article
DE Pandemic H1N1; Non-human primate; Influenza vaccine
ID A H5N1 VIRUS; CYNOMOLGUS MACAQUES; RESPIRATORY-TRACT; INFECTION;
PATHOLOGY; FERRETS; MODEL; MICE; STRAINS; MONKEYS
AB We studied the replication of influenza A/California/07/09 (H1N1) wild type (CA09wt) virus in two non-human primate species and used one of these models to evaluate the immunogenicity and protective efficacy of a live attenuated cold-adapted vaccine, which contains the hemagglutinin and neuraminidase from the H1N1 wild type (wt) virus and six internal protein gene segments of the A/Ann Arbor/6/60 cold-adapted (Ca) master donor virus. We infected African green monkeys (AGMs) and rhesus macaques with 2 x 10(6) TCID50 of CA09wt and CA09ca influenza viruses. The virus CA09wt replicated in the upper respiratory tract of all animals but the titers in upper respiratory tract tissues of rhesus macaques were significant higher than in AGMs (mean peak titers 10(4.5) TCID50/g and 10(2.0) TCID50/g on days 4 and 2 post-infection, respectively: p<0.01). Virus replication was observed in the lungs of all rhesus macaques (10(2.0)-10(5.4) TCID50/g) whereas only 2 out of 4 AGMs had virus recovered from the lungs (10(2.5)-10(3.5) TCID50/g). The CA09ca vaccine virus was attenuated and highly restricted in replication in both AGMs and rhesus macaques. We evaluated the immunogenicity and protective efficacy of the CA09ca vaccine in rhesus macaques because CA09wt virus replicated more efficiently in this species. One or two doses of vaccine were administered intranasally and intratracheally to rhesus macaques. For the two-dose group, the vaccine was administered 4-weeks apart. Immunogenicity was assessed by measuring hemagglutination-inhibiting (HAI) antibodies in the serum and specific IgA antibodies to CA09wt virus in the nasal wash. One or two doses of the vaccine elicited a significant rise in HAI titers (range 40-320). Two doses of CA09ca elicited higher pH1N1-specific IgA titers than in the mock-immunized group (p<0.01). Vaccine efficacy was assessed by comparing titers of CA09wt challenge virus in the respiratory tract of mock-immunized and CA09ca vaccinated monkeys. Significantly lower virus titers were observed in the lungs of vaccinated animals than mock-immunized animals (p <= 0.01). Our results demonstrate that AGMs and rhesus macaques support the replication of pandemic H1N1 influenza virus to different degrees and a cold-adapted pH1N1 vaccine elicits protective immunity against pH1N1 virus infection in rhesus macaques. Published by Elsevier Ltd.
C1 [Boonnak, Kobporn; Paskel, Myeisha; Matsuoka, Yumiko; Vogel, Leatrice; Subbarao, Kanta] NIAID, Emerging Resp Viruses Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Subbarao, K (reprint author), NIAID, Emerging Resp Viruses Sect, Infect Dis Lab, NIH, Bldg 33,Room 3E13C-1,33 North Dr,MSC 3203, Bethesda, MD 20892 USA.
EM KSUBBARAO@niaid.nih.gov
FU Intramural Research Program of National Institute of Allergy and
Infectious Diseases (NIAID), NIH
FX This research was performed as part of a Cooperative Research and
Development Agreement between the Laboratory of Infectious Diseases,
NIAID and MedImmune. This work was supported in part by the Intramural
Research Program of National Institute of Allergy and Infectious
Diseases (NIAID), NIH. We would like to thank Jin Hong and George
Kemble, MedImmune, Inc. for critical reading of this manuscript.
NR 33
TC 11
Z9 11
U1 1
U2 6
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0264-410X
J9 VACCINE
JI Vaccine
PD AUG 17
PY 2012
VL 30
IS 38
BP 5603
EP 5610
DI 10.1016/j.vaccine.2012.06.088
PG 8
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA 000JF
UT WOS:000308381900008
PM 22789506
ER
PT J
AU Patel, ES
Okada, S
Hachey, K
Yang, LJ
Durum, SK
Moreb, JS
Chang, LJ
AF Patel, Ekta S.
Okada, Starlyn
Hachey, Kevin
Yang, Li-jun
Durum, Scott K.
Moreb, Jan S.
Chang, Lung-Ji
TI Regulation of in vitro human T cell development through interleukin-7
deprivation and anti-CD3 stimulation
SO BMC IMMUNOLOGY
LA English
DT Article
DE T cell development; Interleukin-7; T cell receptor; Vbeta repertoire
ID HEMATOPOIETIC STEM-CELLS; BLOOD CD34(+) CELLS; ALPHA-BETA CELLS; CORD
BLOOD; BONE-MARROW; THYMOCYTE DIFFERENTIATION; PROGENITOR CELLS; GENE
REARRANGEMENTS; FUNCTIONALLY MATURE; GROWTH-FACTOR
AB Background: The role of IL-7 and pre-TCR signaling during T cell development has been well characterized in murine but not in human system. We and others have reported that human BM hematopoietic progenitor cells (HPCs) display poor proliferation, inefficient double negative (DN) to double positive (DP) transition and no functional maturation in the in vitro OP9-Delta-like 1 (DL1) culture system.
Results: In this study, we investigated the importance of optimal IL-7 and pre-TCR signaling during adult human T cell development. Using a modified OP9-DL1 culture ectopically expressing IL-7 and Fms-like tyrosine kinase 3 ligand (Flt3L), we demonstrated enhanced T cell precursor expansion. IL-7 removal at various time points during T cell development promoted a slight increase of DP cells; however, these cells did not differentiate further and underwent cell death. As pre-TCR signaling rescues DN cells from programmed cell death, we treated the culture with anti-CD3 antibody. Upon pre-TCR stimulation, the IL-7 deprived T precursors differentiated into CD3(+)TCR alpha beta+DP cells and further matured into functional CD4 T cells, albeit displayed a skewed TCR V beta repertoire.
Conclusions: Our study establishes for the first time a critical control for differentiation and maturation of adult human T cells from HPCs by concomitant regulation of IL-7 and pre-TCR signaling.
C1 [Patel, Ekta S.; Okada, Starlyn; Hachey, Kevin; Chang, Lung-Ji] Univ Florida, Coll Med, Dept Mol Genet & Microbiol, Gainesville, FL 32610 USA.
[Yang, Li-jun] Univ Florida, Coll Med, Dept Pathol Immunol & Lab Med, Gainesville, FL 32610 USA.
[Durum, Scott K.] NCI, Sect Cytokines & Immun, Gainesville, FL 32610 USA.
[Moreb, Jan S.] Univ Florida, Coll Med, Dept Med, Gainesville, FL 32610 USA.
RP Chang, LJ (reprint author), Univ Florida, Coll Med, Dept Mol Genet & Microbiol, 1600 SW Archer Rd,ARB R1-252, Gainesville, FL 32610 USA.
EM lchang@mgm.ufl.edu
FU NIH; amfAR grant [107768]; Yongling Foundation; flow cytometry fund of
UF Shands Cancer Center
FX We thank S. Williams, W. Chou, Dr. Shuhong Han and Yuling Yeh for
technical assistance, Dr. Yung Chang and Dr. Lizi Wu for critical
comments and reading the manuscript, and N. Benson for help with flow
cytometry analysis. ESP was supported by NIH T32 graduate training
grant. The study was supported by amfAR grant 107768, Yongling
Foundation, and flow cytometry fund of UF Shands Cancer Center.
NR 58
TC 2
Z9 3
U1 0
U2 3
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2172
J9 BMC IMMUNOL
JI BMC Immunol.
PD AUG 16
PY 2012
VL 13
AR 46
DI 10.1186/1471-2172-13-46
PG 15
WC Immunology
SC Immunology
GA 037CB
UT WOS:000311077500001
PM 22897934
ER
PT J
AU Lee, M
Mandl, JN
Germain, RN
Yates, AJ
AF Lee, Minyi
Mandl, Judith N.
Germain, Ronald N.
Yates, Andrew J.
TI The race for the prize: T-cell trafficking strategies for optimal
surveillance
SO BLOOD
LA English
DT Article
ID LYMPH-NODES; DENDRITIC CELLS; RECIRCULATING LYMPHOCYTES; REPERTOIRE
DIVERSITY; TCR REPERTOIRE; ANTIGEN; NAIVE; SURVIVAL; EGRESS; RECEPTOR
AB The initiation of T-cell responses requires rare precursors to locate a draining lymph node (dLN) and encounter dendritic cells (DCs) presenting peptide-major histocompatibility complexes (pMHCs). To locate this needle in the haystack rapidly, T cells face an optimization problem-what is the most efficient trafficking strategy for surveillance and recirculation through blood? Two extremes are scanning low numbers of DCs per node with frequent recirculation, or meticulous surveillance with infrequent recirculation. Naive T cells also require stimulation by self-pMHCs. To enable efficient location of both foreign and self, has evolution settled on an optimum time for T cells to spend surveying each lymph node? Using a data-driven mathematical model, we show the most efficient strategy for detecting antigen in a dLN depends on its abundance. Detection of low-density antigen is optimized with systemically slow transit. In contrast, at high densities or if dLN egress is restricted, rapid transit through other nodes is optimal. We argue that blood-lymph recirculation dynamics facilitate a trade-off, and are consistent with dominant roles for the very early detection of rare foreign antigens in a dLN, and the efficient accumulation of signals from systemically distributed self-antigens. (Blood. 2012;120(7):1432-1438)
C1 [Lee, Minyi; Yates, Andrew J.] Albert Einstein Coll Med, Dept Syst & Computat Biol, Bronx, NY 10461 USA.
[Mandl, Judith N.; Germain, Ronald N.] NIAID, Lymphocyte Biol Sect, Lab Syst Biol, NIH, Bethesda, MD 20892 USA.
[Yates, Andrew J.] Albert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 10461 USA.
RP Yates, AJ (reprint author), Albert Einstein Coll Med, Dept Syst & Computat Biol, 1300 Morris Pk Ave, Bronx, NY 10461 USA.
EM andrew.yates@einstein.yu.edu
FU National Institutes of Health [R01 AI093870-01]
FX This study was supported by the National Institutes of Health (R01
AI093870-01 to A.J.Y.).
NR 48
TC 11
Z9 11
U1 1
U2 6
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD AUG 16
PY 2012
VL 120
IS 7
BP 1432
EP 1438
DI 10.1182/blood-2012-04-424655
PG 7
WC Hematology
SC Hematology
GA 009CA
UT WOS:000309001900015
PM 22773385
ER
PT J
AU Backes, S
Shapiro, JS
Sabin, LR
Pham, AM
Reyes, I
Moss, B
Cherry, S
tenOever, BR
AF Backes, Simone
Shapiro, Jillian S.
Sabin, Leah R.
Pham, Alissa M.
Reyes, Ismarc
Moss, Bernard
Cherry, Sara
tenOever, Benjamin R.
TI Degradation of Host MicroRNAs by Poxvirus Poly(A) Polymerase Reveals
Terminal RNA Methylation as a Protective Antiviral Mechanism
SO CELL HOST & MICROBE
LA English
DT Article
ID SMALL SILENCING RNAS; VACCINIA VIRUS; MESSENGER-RNAS; C-ELEGANS; 3'
ENDS; BIOGENESIS; DROSOPHILA; MIRNAS; PROTEINS; SIRNAS
AB The life cycle of several viruses involves host or virally encoded small noncoding RNAs, which play important roles in posttranscriptional regulation. Small noncoding RNAs include microRNAs (miRNAs), which modulate the transcriptome, and small interfering RNAs (siRNAs), which are involved in pathogen defense in plants, worms, and insects. We show that insect and mammalian poxviruses induce the degradation of host miRNAs. The virally encoded poly(A) polymerase, which polyadenylates viral transcripts, also mediates 3' polyadenylation of host miRNAs, resulting in their degradation by the host machinery. In contrast, siRNAs, which are protected by 2'O-methylation (2'OMe), were not targeted by poxviruses. These findings suggest that poxviruses may degrade host miRNAs to promote replication and that virus-mediated small RNA degradation likely contributed to 2'OMe evolution.
C1 [Sabin, Leah R.; Cherry, Sara] Univ Penn, Dept Microbiol, Philadelphia, PA 19104 USA.
[Backes, Simone; Shapiro, Jillian S.; Pham, Alissa M.; Reyes, Ismarc; tenOever, Benjamin R.] Mt Sinai Sch Med, Dept Microbiol, New York, NY 10029 USA.
[Moss, Bernard] NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Cherry, S (reprint author), Univ Penn, Dept Microbiol, Philadelphia, PA 19104 USA.
EM cherrys@mail.med.upenn.edu; benjamin.tenoever@mssm.edu
OI Sabin, Leah/0000-0003-1757-7415
FU Burroughs Wellcome Fund; National Institutes of Health [R01AI074951,
U54AI057168]; Army Research Office [59471LS]
FX S.C. and B.R.t. acknowledge the gracious support of the Burroughs
Wellcome Fund. This work was supported by grants from the National
Institutes of Health (R01AI074951,U54AI057168) to S.C. and the Army
Research Office (59471LS) to B.R.t. Additionally, we would like to thank
Drs. G. Hannon (HHMI, Cold Spring Harbor Laboratories) for performing a
subset of the deep sequencing, R. Condit (University of Florida,
Gainesville) for the VACV E1L antibody, S.A. Perera (Great Lakes
Forestry Centre, Ontario, Canada) for Amsacta moorei entomopoxvirus
(AMEV), and R. Clem (Kansas State University, Manhattan, KS) for Amsacta
moorei Ld652 cells.
NR 75
TC 32
Z9 35
U1 1
U2 17
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1931-3128
J9 CELL HOST MICROBE
JI Cell Host Microbe
PD AUG 16
PY 2012
VL 12
IS 2
BP 200
EP 210
DI 10.1016/j.chom.2012.05.019
PG 11
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA 998UM
UT WOS:000308265900010
PM 22901540
ER
PT J
AU Grooman, B
Fujiwara, I
Otey, C
Upadhyaya, A
AF Grooman, Brian
Fujiwara, Ikuko
Otey, Carol
Upadhyaya, Arpita
TI Morphology and Viscoelasticity of Actin Networks Formed with the
Mutually Interacting Crosslinkers: Palladin and Alpha-actinin
SO PLOS ONE
LA English
DT Article
ID CYTOSKELETAL POLYMER NETWORKS; F-ACTIN; MECHANICAL-PROPERTIES; FILAMENT
NETWORKS; BINDING PROTEINS; CELL MECHANICS; GELS; DETERMINES;
ELASTICITY; STIFFNESS
AB Actin filaments and associated actin binding proteins play an essential role in governing the mechanical properties of eukaryotic cells. Even though cells have multiple actin binding proteins (ABPs) that exist simultaneously to maintain the structural and mechanical integrity of the cellular cytoskeleton, how these proteins work together to determine the properties of actin networks is not clearly understood. The ABP, palladin, is essential for the maintenance of cell morphology and the regulation of cell movement. Palladin coexists with alpha-actinin in stress fibers and focal adhesions and binds to both actin and alpha-actinin. To obtain insight into how mutually interacting actin crosslinking proteins modulate the properties of actin networks, we characterized the micro-structure and mechanics of actin networks crosslinked with palladin and alpha-actinin. We first showed that palladin crosslinks actin filaments into bundled networks which are viscoelastic in nature. Our studies also showed that composite networks of alpha-actinin/palladin/actin behave very similar to pure palladin or pure alpha-actinin networks. However, we found evidence that palladin and alpha-actinin synergistically modify network viscoelasticity. To our knowledge, this is the first quantitative characterization of the physical properties of actin networks crosslinked with two mutually interacting crosslinkers.
C1 [Grooman, Brian] Univ Maryland, Dept Phys, College Pk, MD 20742 USA.
[Fujiwara, Ikuko] NHLBI, NIH, Bethesda, MD 20892 USA.
[Otey, Carol] Univ N Carolina, Dept Cell & Mol Physiol, Chapel Hill, NC USA.
[Upadhyaya, Arpita] Univ Maryland, Dept Phys, College Pk, MD 20742 USA.
[Upadhyaya, Arpita] Univ Maryland, Inst Phys Sci & Technol, College Pk, MD 20742 USA.
RP Grooman, B (reprint author), Univ Maryland, Dept Phys, College Pk, MD 20742 USA.
EM arpitau@umd.edu
RI Fujiwara, Ikuko/H-5717-2016
OI Fujiwara, Ikuko/0000-0002-9361-636X
FU Alfred P. Sloan Foundation; National Science Foundation [112170]
FX This work has been supported by the Alfred P. Sloan Foundation and the
National Science Foundation (Grant 112170). The funders had no role in
study design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 44
TC 7
Z9 7
U1 1
U2 17
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 16
PY 2012
VL 7
IS 8
AR e42773
DI 10.1371/journal.pone.0042773
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 993AN
UT WOS:000307824300015
PM 22916157
ER
PT J
AU Wang, XY
Keefe, KM
Jensen-Taubman, SM
Yang, DL
Yan, K
Linnoila, RI
AF Wang, Xiao-Yang
Keefe, Kathleen M.
Jensen-Taubman, Sandra M.
Yang, Danlei
Yan, Kai
Linnoila, R. Ilona
TI Novel Method for Isolation of Murine Clara Cell Secretory
Protein-Expressing Cells with Traces of Stemness
SO PLOS ONE
LA English
DT Article
ID HUMAN AIRWAY EPITHELIUM; MOUSE LUNG; BRONCHIOLAR EPITHELIUM;
IDENTIFICATION; DIFFERENTIATION; PROLIFERATION; DEFICIENCY; EXPOSURE;
RENEWAL; NUMBER
AB Clara cells are non-ciliated, secretory bronchiolar epithelial cells that serve to detoxify harmful inhaled substances. Clara cells also function as stem/progenitor cells for repair in the bronchioles. Clara cell secretory protein (CCSP) is specifically expressed in pulmonary Clara cells and is widely used as a Clara cell marker. In addition CCSP promoter is commonly used to direct gene expression into the lung in transgenic models. The discovery of CCSP immunoreactivity in plasma membranes of airway lining cells prompted us to explore the possibility of enriching Clara cells by flow cytometry. We established a novel and simple method for the isolation of CCSP-expressing cell Clara cells using a combination of mechanical and enzymatic dissociation followed by flow cytometry sorting technology. We showed that similar to 25% of dissociated cells from whole lung expressed CCSP. In the resulting preparation, up to 98% of cells expressed CCSP. Notably, we found that several common stem cell markers including CD44, CD133, Sca-1 and Sox2 were expressed in CCSP+ cells. Moreover, CCSP+ cells were able to form spheroid colonies in vitro with 0.97 parts per thousand efficiency. Parallel studies in vivo confirmed that a small population of CCSP- expressing cells in mouse airways also demonstrates stem cell-like properties such as label retention and harboring rare bronchioalveolar stem cells (BASCs) in terminal bronchioles (TBs). We conclude that CCSP+ cells exhibit a number of stem cell-like features including stem cell marker expression, bronchosphere colony formation and self-renewal ability. Clara cell isolation by flow cytometry sorting is a useful method for investigating the function of primary Clara cells in stem cell research and mouse models.
C1 [Wang, Xiao-Yang; Keefe, Kathleen M.; Jensen-Taubman, Sandra M.; Yang, Danlei; Yan, Kai; Linnoila, R. Ilona] NCI, Cell & Canc Biol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Wang, XY (reprint author), NCI, Cell & Canc Biol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM xiaoyangwang@gmail.com; Linnoila@mail.nih.gov
FU National Cancer Institute at the National Institutes of Health
FX This study was supported by the Intramural Research Program of the
National Cancer Institute at the 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 41
TC 3
Z9 5
U1 0
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 16
PY 2012
VL 7
IS 8
AR e43008
DI 10.1371/journal.pone.0043008
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 993AN
UT WOS:000307824300024
PM 22916196
ER
PT J
AU Ostrander, EA
AF Ostrander, Elaine A.
TI Both Ends of the Leash - The Human Links to Good Dogs with Bad Genes
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Review
ID GENOME-WIDE ASSOCIATION; ROD-CONE DEGENERATION; LEBER CONGENITAL
AMAUROSIS; HOGG-DUBE-SYNDROME; DOMESTIC DOG; RENAL CYSTADENOCARCINOMA;
RETINITIS-PIGMENTOSA; CHILDHOOD BLINDNESS; HISTIOCYTIC SARCOMA; CANINE
EPILEPSY
C1 NHGRI, NIH, Bethesda, MD 20892 USA.
RP Ostrander, EA (reprint author), NHGRI, NIH, 50 South Dr,Bldg 50,Rm 5351, Bethesda, MD 20892 USA.
EM eostrand@mail.nih.gov
OI Ostrander, Elaine/0000-0001-6075-9738
FU Intramural NIH HHS [ZIA HG200377-01]
NR 86
TC 28
Z9 28
U1 0
U2 43
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD AUG 16
PY 2012
VL 367
IS 7
BP 636
EP 646
DI 10.1056/NEJMra1204453
PG 11
WC Medicine, General & Internal
SC General & Internal Medicine
GA 988NB
UT WOS:000307496600007
PM 22894576
ER
PT J
AU Moore, HM
Kelly, A
McShane, LM
Vaught, J
AF Moore, Helen M.
Kelly, Andrea
McShane, Lisa M.
Vaught, Jim
TI Biospecimen reporting for improved study quality (BRISQ)
SO CLINICA CHIMICA ACTA
LA English
DT Letter
C1 [Moore, Helen M.; Vaught, Jim] NCI, Off Biorepositories & Biospecimen Res, NIH, US Dept HHS, Bethesda, MD 20892 USA.
[Kelly, Andrea] Rose Li & Associates Inc, Bethesda, MD USA.
[McShane, Lisa M.] NCI, Biometr Res Branch, NIH, US Dept HHS, Bethesda, MD 20892 USA.
RP Moore, HM (reprint author), NCI, Off Biorepositories & Biospecimen Res, NIH, US Dept HHS, 11400 Rockville Pike,Suite 700, Bethesda, MD 20892 USA.
EM moorehe@mail.nih.gov
NR 4
TC 12
Z9 12
U1 0
U2 0
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0009-8981
J9 CLIN CHIM ACTA
JI Clin. Chim. Acta
PD AUG 16
PY 2012
VL 413
IS 15-16
BP 1305
EP 1305
DI 10.1016/j.cca.2012.04.013
PG 1
WC Medical Laboratory Technology
SC Medical Laboratory Technology
GA 960EH
UT WOS:000305370300029
PM 22543057
ER
PT J
AU Sitaram, A
Dennis, MK
Chaudhuri, R
De Jesus-Rojas, W
Tenza, D
Setty, SRG
Wood, CS
Sviderskaya, EV
Bennett, DC
Raposo, G
Bonifacino, JS
Marks, MS
AF Sitaram, Anand
Dennis, Megan K.
Chaudhuri, Rittik
De Jesus-Rojas, Wilfredo
Tenza, Daniele
Setty, Subba Rao Gangi
Wood, Christopher S.
Sviderskaya, Elena V.
Bennett, Dorothy C.
Raposo, Graca
Bonifacino, Juan S.
Marks, Michael S.
TI Differential recognition of a dileucine-based sorting signal by AP-1 and
AP-3 reveals a requirement for both BLOC-1 and AP-3 in delivery of OCA2
to melanosomes
SO MOLECULAR BIOLOGY OF THE CELL
LA English
DT Article
ID LYSOSOME-RELATED ORGANELLES; HERMANSKY-PUDLAK-SYNDROME; SUSCEPTIBILITY
FACTOR DYSBINDIN; VIRUS TYPE-1 NEF; DI-LEUCINE; PROTEIN TRAFFICKING;
MEMBRANE-PROTEINS; SKIN PIGMENTATION; SYNAPTIC VESICLES; COMPLEX-1
BLOC-1
AB Cell types that generate unique lysosome-related organelles (LROs), such as melanosomes in melanocytes, populate nascent LROs with cargoes that are diverted from endosomes. Cargo sorting toward melanosomes correlates with binding via cytoplasmically exposed sorting signals to either heterotetrameric adaptor AP-1 or AP-3. Some cargoes bind both adaptors, but the relative contribution of each adaptor to cargo recognition and their functional interactions with other effectors during transport to melanosomes are not clear. Here we exploit targeted mutagenesis of the acidic dileucine-based sorting signal in the pigment cell-specific protein OCA2 to dissect the relative roles of AP-1 and AP-3 in transport to melanosomes. We show that binding to AP-1 or AP-3 depends on the primary sequence of the signal and not its position within the cytoplasmic domain. Mutants that preferentially bound either AP-1 or AP-3 each trafficked toward melanosomes and functionally complemented OCA2 deficiency, but AP-3 binding was necessary for steady-state melanosome localization. Unlike tyrosinase, which also engages AP-3 for optimal melanosomal delivery, both AP-1- and AP-3-favoring OCA2 variants required BLOC-1 for melanosomal transport. These data provide evidence for distinct roles of AP-1 and AP-3 in OCA2 transport to melanosomes and indicate that BLOC-1 can cooperate with either adaptor during cargo sorting to LROs.
C1 [Sitaram, Anand; Dennis, Megan K.; De Jesus-Rojas, Wilfredo; Setty, Subba Rao Gangi; Wood, Christopher S.; Marks, Michael S.] Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA.
[Sitaram, Anand; Dennis, Megan K.; De Jesus-Rojas, Wilfredo; Setty, Subba Rao Gangi; Wood, Christopher S.; Marks, Michael S.] Univ Penn, Dept Physiol, Philadelphia, PA 19104 USA.
[Sitaram, Anand] Univ Penn, Cell & Mol Biol Grad Grp, Philadelphia, PA 19104 USA.
[Chaudhuri, Rittik; Bonifacino, Juan S.] NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA.
[Tenza, Daniele; Raposo, Graca] Inst Curie, Sect Rech, F-75005 Paris, France.
[Tenza, Daniele; Raposo, Graca] CNRS, UMR 144, F-75005 Paris, France.
[Sviderskaya, Elena V.; Bennett, Dorothy C.] Univ London, Biomed Sci Res Ctr, London SW17 0RE, England.
RP Marks, MS (reprint author), Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA.
EM marksm@mail.med.upenn.edu
RI Bennett, Dorothy/C-2418-2008;
OI Bennett, Dorothy/0000-0002-3639-7527; Dennis, Megan/0000-0002-8986-5021;
Marks, Michael/0000-0001-7435-7262; Bonifacino, Juan
S./0000-0002-5673-6370
FU National Institutes of Health Grant from the National Eye Institute [R01
EY015625]; Institut Curie and Centre National de la Recherche
Scientifique; Eunice Kennedy Shriver National Institute of Child Health
and Human Development; Wellcome Trust [078327]; [T32 GM007229]; [T32
HL007971]; [K12 GM081259]
FX We thank Victor Faundez and Andrew Peden for generous gifts of
antibodies. This work was supported by National Institutes of Health
Grant R01 EY015625 from the National Eye Institute (to M.S.M.), Training
Grants T32 GM007229 and T32 HL007971 (for A.S.) and K12 GM081259 (for
M.K.D.), the Institut Curie and Centre National de la Recherche
Scientifique (for G.R.), the Intramural Program of the Eunice Kennedy
Shriver National Institute of Child Health and Human Development (for
J.S.B.), and Wellcome Trust Grant 078327 (to E.V.S. and D.C.B.).
NR 70
TC 19
Z9 21
U1 0
U2 7
PU AMER SOC CELL BIOLOGY
PI BETHESDA
PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA
SN 1059-1524
J9 MOL BIOL CELL
JI Mol. Biol. Cell
PD AUG 15
PY 2012
VL 23
IS 16
BP 3178
EP 3192
DI 10.1091/mbc.E11-06-0509
PG 15
WC Cell Biology
SC Cell Biology
GA 052SX
UT WOS:000312219900015
PM 22718909
ER
PT J
AU Qiu, HF
Hu, CH
Gaur, NA
Hinnebusch, AG
AF Qiu, Hongfang
Hu, Cuihua
Gaur, Naseem A.
Hinnebusch, Alan G.
TI Pol II CTD kinases Bur1 and Kin28 promote Spt5 CTR-independent
recruitment of Paf1 complex
SO EMBO JOURNAL
LA English
DT Article
DE CTD; Paf1C; Spt5; transcription elongation
ID RNA-POLYMERASE-II; C-TERMINAL DOMAIN; COTRANSCRIPTIONAL HISTONE
MODIFICATION; TRANSCRIPTION TERMINATION; H2B MONOUBIQUITINATION;
ELONGATION; PHOSPHORYLATION; METHYLATION; ASSOCIATION; SUBUNIT
AB Paf1 complex (Paf1C) is a transcription elongation factor whose recruitment is stimulated by Spt5 and the CDKs Kin28 and Bur1, which phosphorylate the Pol II C-terminal domain (CTD) on Serines 2, 5, and 7. Bur1 promotes Paf1C recruitment by phosphorylating C-terminal repeats (CTRs) in Spt5, and we show that Kin28 enhances Spt5 phosphorylation by promoting Bur1 recruitment. It was unclear, however, whether CTD phosphorylation by Kin28 or Bur1 also stimulates Paf1C recruitment. We find that Paf1C and its Cdc73 subunit bind diphosphorylated CTD repeats (pCTD) and phosphorylated Spt5 CTRs (pCTRs) in vitro, and that cdc73 mutations eliminating both activities reduce Paf1C recruitment in vivo. Phosphomimetic (acidic) substitutions in the Spt5 CTR sustain high-level Paf1C recruitment in otherwise wild-type cells, but not following inactivation of Bur1 or Kin28. Furthermore, inactivating the pCTD/pCTR-interaction domain (PCID) in Cdc73 decreases Paf1C-dependent histone methylation in cells containing non-phosphorylatable Spt5 CTRs. These results identify an Spt5 pCTR-independent pathway of Paf1C recruitment requiring Kin28, Bur1, and the Cdc73 PCID. We propose that pCTD repeats and Spt5 pCTRs provide separate interaction surfaces that cooperate to ensure high-level Paf1C recruitment. The EMBO Journal (2012) 31, 3494-3505. doi:10.1038/emboj.2012.188; Published online 13 July 2012
C1 [Qiu, Hongfang; Hu, Cuihua; Gaur, Naseem A.; Hinnebusch, Alan G.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Lab Gene Regulat & Dev, Bethesda, MD USA.
RP Hinnebusch, AG (reprint author), NICHHD, Lab Gene Regulat & Dev, NIH, Bldg 6,Room 230, Bethesda, MD 20892 USA.
EM ahinnebusch@nih.gov
OI Gaur, Naseem/0000-0002-1224-8789
FU Intramural Research Program of the National Institute of Child Health
and Human Development (NICHD), National Institutes of Health (NIH)
FX We thank Tom Dever for excellent suggestions and advice; Fred Winston
and Steven Hahn for plasmids; and Karen Arndt, Grant Hartzog, and Steven
Hahn for antibodies. We also appreciate Kevan Shokat's kind gift of
3MB-PP1 at the outset of this study. We thank Andy VanDemark and Karen
Arndt for critical reading of the manuscript and for communicating
results prior to publication. This research was supported by the
Intramural Research Program of the National Institute of Child Health
and Human Development (NICHD), National Institutes of Health (NIH).
NR 43
TC 28
Z9 28
U1 0
U2 9
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0261-4189
J9 EMBO J
JI Embo J.
PD AUG 15
PY 2012
VL 31
IS 16
BP 3494
EP 3505
DI 10.1038/emboj.2012.188
PG 12
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 993SK
UT WOS:000307879700013
PM 22796944
ER
PT J
AU Leandri, M
Ghignotti, M
Emionite, L
Leandri, S
Cilli, M
AF Leandri, Massimo
Ghignotti, Mariaisabella
Emionite, Laura
Leandri, Silia
Cilli, Michele
TI Electrophysiological features of the mouse tail nerves and their changes
in chemotherapy induced peripheral neuropathy (CIPN)
SO JOURNAL OF NEUROSCIENCE METHODS
LA English
DT Article
DE Tail nerve; Mouse; Compound action potential; Neuropathy; Chemotherapy
ID SENSORY NEUROPATHY; AXONAL-TRANSPORT; RAT; CONDUCTION; MICE; TAXOL;
IMPULSES; NEURONS
AB Electrophysiology of tail nerves in rodents has been demonstrated a reliable method to investigate models of peripheral neuropathies. Nevertheless, data concerning mouse models are lacking. We assessed the normal features of sensory and motor conduction of tail nerves in adult mice. We found that, as in rats, a sensory compound action potential and motor responses could be recorded with the non invasive and highly reliable technique proposed, especially if bipolar derivations were used. We also investigated the changes related to chemotherapy induced peripheral neuropathy (CIPN) after paclitaxel treatment (times 1 and 2), compared to pre-treatment (time 0) and to controls. It was found that only the sensory compound action potential was involved in CIPN, with decrease in amplitude and conduction velocity, suggesting a significant reduction in number of fast conducting fibres and a correspondent increase in the number of slow conducting ones, although the total amount of active myelinated fibres was deemed to be unchanged through time 0, time 1 and time 2. The results obtained in CIPN provide new functional evidence about the involvement of sensory fibres and may help in better understanding the underlying mechanisms. (C) 2012 Elsevier B.V. All rights reserved.
C1 [Leandri, Massimo; Ghignotti, Mariaisabella; Leandri, Silia] Univ Genoa, Interuniv Ctr Pain Neurophysiol, I-16146 Genoa, Italy.
[Leandri, Massimo] Univ Genoa, Dept Neurosci Rehabil Ophtalmol & Genet, I-16132 Genoa, Italy.
[Emionite, Laura; Cilli, Michele] Natl Canc Inst, Anim Facil, I-16132 Genoa, Italy.
RP Leandri, M (reprint author), Univ Genoa, Interuniv Ctr Pain Neurophysiol, Via Dodecaneso 35, I-16146 Genoa, Italy.
EM massimo.leandri@unige.it
OI Leandri, Massimo/0000-0002-5197-7431
FU CIND; Italian Ministry of Health (OnRehab project)
FX This work has been carried out at the Interuniversity Centre for Pain
Neurophysiology (CIND), University of Genova, and at the Animal
Facility, National Cancer Institute, Genova. Funding has been provided
by CIND, with statutory funds, and by the Italian Ministry of Health
(OnRehab project).
NR 24
TC 8
Z9 8
U1 0
U2 1
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0165-0270
J9 J NEUROSCI METH
JI J. Neurosci. Methods
PD AUG 15
PY 2012
VL 209
IS 2
BP 403
EP 409
DI 10.1016/j.jneumeth.2012.07.005
PG 7
WC Biochemical Research Methods; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA 007OL
UT WOS:000308897900018
PM 22800858
ER
PT J
AU Yin, JJ
Liu, J
Ehrenshaft, M
Roberts, JE
Fu, PP
Mason, RP
Zhao, BZ
AF Yin, Jun-Jie
Liu, Jun
Ehrenshaft, Marilyn
Roberts, Joan E.
Fu, Peter P.
Mason, Ronald P.
Zhao, Baozhong
TI Phototoxicity of nano titanium dioxides in HaCaT
keratinocytes-Generation of reactive oxygen species and cell damage
SO TOXICOLOGY AND APPLIED PHARMACOLOGY
LA English
DT Article
DE TiO2 nanoparticles; Phototoxicity; Reactive oxygen species (ROS); Lipid
peroxidation; Human HaCaT keratinocytes; ESR; Oximetry; Immuno-spin
trapping
ID PROTEIN RADICAL FORMATION; SINGLET OXYGEN; PHOTOCATALYTIC ACTIVITY; TIO2
NANOPARTICLES; OXIDATIVE STRESS; IN-VITRO; TOXICITY; EPR; UVA;
CYTOTOXICITY
AB Nano-sized titanium dioxide (TiO2) is among the top five widely used nanomaterials for various applications. In this study, we determine the phototoxicity of TiO2 nanoparticles (nano-TiO2) with different molecular sizes and crystal forms (anatase and rutile) in human skin keratinocytes under UVA irradiation. Our results show that all nano-TiO2 particles caused phototoxicity, as determined by the MIS assay and by cell membrane damage measured by the lactate dehydrogenase (LDH) assay, both of which were UVA dose- and nano-TiO2 dose-dependent. The smaller the particle size of the nano-TiO2 the higher the cell damage. The rutile form of nano-TiO2 showed less phototoxicity than anatase nano-TiO2. The level of photocytotoxicity and cell membrane damage is mainly dependent on the level of reactive oxygen species (ROS) production. Using polyunsaturated lipids in plasma membranes and human serum albumin as model targets, and employing electron spin resonance (ESR) oximetry and immuno-spin trapping as unique probing methods, we demonstrated that UVA irradiation of nano-TiO2 can induce significant cell damage, mediated by lipid and protein peroxidation. These overall results suggest that nano-TiO2 is phototoxic to human skin keratinocytes, and that this phototoxicity is mediated by ROS generated during UVA irradiation. (C) 2012 Elsevier Inc. All rights reserved.
C1 [Liu, Jun; Zhao, Baozhong] Natl Ctr Nanosci & Technol, CAS Key Lab Biomed Effects Nanomat & Nanosafety, Beijing 100190, Peoples R China.
[Yin, Jun-Jie] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA.
[Ehrenshaft, Marilyn; Mason, Ronald P.] NIEHS, Lab Toxicol & Pharmacol, NIH, Res Triangle Pk, NC 27709 USA.
[Roberts, Joan E.] Fordham Univ, New York, NY 10023 USA.
[Fu, Peter P.] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA.
RP Zhao, BZ (reprint author), Natl Ctr Nanosci & Technol, CAS Key Lab Biomed Effects Nanomat & Nanosafety, Beijing 100190, Peoples R China.
EM zhaobz@nanoctr.cn
RI Zhao, Baozhong/B-5865-2011; Yin, Jun Jie /E-5619-2014
FU FY11 FDA Nanotechnology CORES Program; Intramural Research Program of
the NIH, National Institute of Environmental Health Sciences
FX This article is not an official US Food and Drug Administration (FDA)
guidance or policy statement. No official support or endorsement by the
US FDA is intended or should be inferred. This work was supported by a
regulatory science grant under the FY11 FDA Nanotechnology CORES Program
(JJ Yin) and the Intramural Research Program of the NIH, National
Institute of Environmental Health Sciences. The authors are indebted to
Dr. Jianxun Xu for his help in SEM image analysis, Dr. Zhanjun Gu,
Yeteng Zhong for their help in XRD analysis, and Dr. Ann Motten, NIEHS,
for critical reading of the manuscript.
NR 42
TC 57
Z9 60
U1 4
U2 56
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0041-008X
EI 1096-0333
J9 TOXICOL APPL PHARM
JI Toxicol. Appl. Pharmacol.
PD AUG 15
PY 2012
VL 263
IS 1
BP 81
EP 88
DI 10.1016/j.taap.2012.06.001
PG 8
WC Pharmacology & Pharmacy; Toxicology
SC Pharmacology & Pharmacy; Toxicology
GA 984RK
UT WOS:000307208900011
PM 22705594
ER
PT J
AU Zhan, LJ
Zhang, H
Zhang, Q
Woods, CG
Chen, YY
Xue, P
Dong, J
Tokar, EJ
Xu, YY
Hou, YY
Fu, JQ
Yarborough, K
Wang, AP
Qu, WD
Waalkes, MP
Andersen, ME
Pi, JB
AF Zhan, Lijuan
Zhang, Hao
Zhang, Qiang
Woods, Courtney G.
Chen, Yanyan
Xue, Peng
Dong, Jian
Tokar, Erik J.
Xu, Yuanyuan
Hou, Yongyong
Fu, Jingqi
Yarborough, Kathy
Wang, Aiping
Qu, Weidong
Waalkes, Michael P.
Andersen, Melvin E.
Pi, Jingbo
TI Regulatory role of KEAP1 and NRF2 in PPAR gamma expression and
chemoresistance in human non-small-cell lung carcinoma cells
SO FREE RADICAL BIOLOGY AND MEDICINE
LA English
DT Article
DE NRF2; KEAP1; PPAR gamma; Arsenic trioxide; Chemoresistance; NSCLC; Lung
cancer; Free radicals
ID ACTIVATED RECEPTOR-GAMMA; INDUCED ANTIOXIDANT RESPONSE; ACUTE
PROMYELOCYTIC LEUKEMIA; CANCER STEM-CELLS; IN-VITRO; A549 CELLS; HUMAN
KERATINOCYTES; ADAPTIVE RESPONSE; ARSENIC TRIOXIDE; SIDE-POPULATION
AB The nuclear factor-E2-related factor 2 (NRF2) serves as a master regulator in cellular defense against oxidative stress and chemical detoxification. However, persistent activation of NRF2 resulting from mutations in NRF2 and/or downregulation of or mutations in its suppressor, Kelch-like ECH-associated protein 1 (KEAP1), is associated with tumorigenicity and chemoresistance of non-small-cell lung carcinomas (NSCLCs). Thus, inhibiting the NRF2-mediated adaptive antioxidant response is widely considered a promising strategy to prevent tumor growth and reverse chemoresistance in NSCLCs. Unexpectedly, stable knockdown of KEAP1 by lentiviral shRNA sensitized three independent NSCLC cell lines (A549, HTB-178, and HTB-182) to multiple chemotherapeutic agents, including arsenic trioxide (As2O3), etoposide, and doxorubicin, despite moderately increased NRF2 levels. In lung adenocarcinoma epithelial A549 cells, silencing of KEAP1 augmented the expression of peroxisome proliferator-activated receptor gamma (PPAR gamma) and genes associated with cell differentiation, including E-cadherin and gelsolin. In addition, KEAP1-knockdown A549 cells displayed attenuated expression of the proto-oncogene cyclin D1 and markers for cancer stem cells (CSCs) and reduced nonadherent sphere formation. Moreover, deficiency of KEAP1 led to elevated induction of PPAR gamma in response to As2O3. Pretreatment of A549 cells with PPAR gamma agonists activated PPAR gamma and augmented the cytotoxicity of As2O3. A mathematical model was formulated to advance a hypothesis that differential regulation of PPAR gamma and detoxification enzymes by KEAP1 and NRF2 may underpin the observed landscape changes in chemosensitivity. Collectively, suppression of KEAP1 expression in human NSCLC cells resulted in sensitization to chemotherapeutic agents, which may be attributed to activation of PPAR gamma and subsequent alterations in cell differentiation and CSC abundance. (C) 2012 Elsevier Inc. All rights reserved.
C1 [Zhan, Lijuan; Zhang, Hao; Zhang, Qiang; Woods, Courtney G.; Chen, Yanyan; Xue, Peng; Dong, Jian; Hou, Yongyong; Fu, Jingqi; Yarborough, Kathy; Andersen, Melvin E.] Hamner Inst Hlth Sci, Inst Chem Safety Sci, Res Triangle Pk, NC 27709 USA.
[Zhan, Lijuan; Wang, Aiping; Pi, Jingbo] Chinese Acad Med Sci, Inst Mat Med, Beijing 100050, Peoples R China.
[Zhan, Lijuan; Wang, Aiping; Pi, Jingbo] Peking Union Med Coll, Beijing 100021, Peoples R China.
[Zhang, Hao; Qu, Weidong] Fudan Univ, Sch Publ Hlth, Shanghai 200433, Peoples R China.
[Chen, Yanyan] China Med Univ, Sch Clin Sci 1, Shenyang, Peoples R China.
[Tokar, Erik J.; Xu, Yuanyuan; Waalkes, Michael P.] NIEHS, Natl Toxicol Program Labs, Div Natl Toxicol Program, Res Triangle Pk, NC 27709 USA.
RP Zhang, Q (reprint author), Hamner Inst Hlth Sci, Inst Chem Safety Sci, Res Triangle Pk, NC 27709 USA.
EM qzhang@thehamner.org; jpi@thehamner.org
RI xue, peng/K-4159-2015;
OI Andersen, Melvin/0000-0002-3894-4811
FU NIH [ES016005]; DOW Chemical Co.; Unilever; American Chemical Council
FX This research was supported in part by the NIH Grant ES016005 (to J.P.),
the DOW Chemical Co. (to M.E.A.), and Unilever (to M.E.A.). We are
grateful for Drs. Bin Sun and Joe Trask for their technical assistance.
The content is solely the responsibility of the authors. All authors
have agreed to its content. M.E.A. received some funding from DOW
Chemical Co. and Unilever. L.Z., HZ., Q.Z., C.G.W., P.X., Y.H., J.F.,
K.Y., M.E.A., and J.P. are employees of The Hamner Institutes for Health
Sciences. The Hamner is a 501(c)3 not-for-profit organization that has a
diverse research portfolio that includes funding from the American
Chemical Council, a trade association that represents chemical
manufacturers. This article may be the work product of an employee or
group of employees of the National Institute of Environmental Health
Sciences (NIEHS), National Institutes of Health (NIH): however, the
statements, opinions, or conclusions contained herein do not necessarily
represent the statements, opinions, or conclusions of the NIEHS, the
NIH, or the U.S. government.
NR 54
TC 25
Z9 26
U1 2
U2 20
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0891-5849
J9 FREE RADICAL BIO MED
JI Free Radic. Biol. Med.
PD AUG 15
PY 2012
VL 53
IS 4
BP 758
EP 768
DI 10.1016/j.freeradbiomed.2012.05.041
PG 11
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA 994GY
UT WOS:000307920100012
PM 22684020
ER
PT J
AU Tanaka, M
Jaruga, P
Kupfer, PA
Leumann, CJ
Dizdaroglu, M
Sonntag, WE
Chock, PB
AF Tanaka, Mikiei
Jaruga, Pawel
Kuepfer, Pascal A.
Leumann, Christian J.
Dizdaroglu, Miral
Sonntag, William E.
Chock, P. Boon
TI RNA oxidation catalyzed by cytochrome c leads to its depurination and
cross-linking, which may facilitate cytochrome c release from
mitochondria
SO FREE RADICAL BIOLOGY AND MEDICINE
LA English
DT Article
DE RNA oxidation; Cytochrome c release; Cross-link; Abasic site;
8-Hydroxyguanosine; Free radicals
ID MILD COGNITIVE IMPAIRMENT; DNA-POLYMERASE BETA; HYDROGEN-PEROXIDE;
MESSENGER-RNA; MAMMALIAN CHROMATIN; INTERMEMBRANE SPACE;
ALZHEIMERS-DISEASE; MASS-SPECTROMETRY; ABASIC SITES; EARLY EVENT
AB Growing evidence indicates that RNA oxidation is correlated with a number of age-related neurodegenerative diseases, and RNA oxidation has also been shown to induce dysfunction in protein synthesis. Here we study in vitro RNA oxidation catalyzed by cytochrome c (cyt c)/H2O2 or by the Fe(II)/ascorbate/H2O2 system. Our results reveal that the products of RNA oxidation vary with the oxidant used. Guanosine residues are preferentially oxidized by cyt c/H2O2 relative to the Fe(II)/ascorbate/H2O2 system. GC/MS and LC/MS analyses demonstrated that the guanine base was not only oxidized but also depurinated to form an abasic sugar moiety. Results from gel electrophoresis and HPLC analyses show that RNA formed a crosslinked complex with cyt c in an H2O2 concentration-dependent manner. Furthermore, when cyt c was associated with liposomes composed of cardiolipin/phosphatidylcholine, and incubated with RNA and H2O2, it was found cross-linked with the oxidized RNA and dissociated from the liposome. Results of the quantitative analysis indicate that the release of the cyt c from the liposome is facilitated by the formation of an RNA-cyt c cross-linked complex. Thus, RNA oxidation may facilitate the release of cyt c from the mitochondrial membrane to induce apoptosis in response to oxidative stress. Published by Elsevier Inc.
C1 [Tanaka, Mikiei; Chock, P. Boon] NHLBI, Biochem Lab, NIH, Bethesda, MD 20892 USA.
[Tanaka, Mikiei; Sonntag, William E.] Univ Oklahoma, Hlth Sci Ctr, Dept Geriatr Med, Reynolds Oklahoma Ctr Aging, Oklahoma City, OK 73104 USA.
[Jaruga, Pawel; Dizdaroglu, Miral] NIST, Chem Sci & Technol Lab, Gaithersburg, MD 20899 USA.
[Kuepfer, Pascal A.; Leumann, Christian J.] Univ Bern, Dept Chem & Biochem, CH-3012 Bern, Switzerland.
RP Chock, PB (reprint author), NHLBI, Biochem Lab, NIH, Bldg 3, Bethesda, MD 20892 USA.
EM mikiei.tanaka@usuhs.edu; bchock@nih.gov
RI Jaruga, Pawel/M-4378-2015;
OI Leumann, Christian/0000-0002-7996-7083
FU National Institutes of Health [AG11370, NS056218]; National Heart, Lung,
and Blood Institute
FX The authors acknowledge the late Dr. Earl R. Stadtman, an eminent
scientist and a distinguished mentor, for his initiation and support of
this project. This research was supported, in whole, by the Intramural
Research Program of the National Institutes of Health; National Heart,
Lung, and Blood Institute; and NIH Grants AG11370 and NS056218. Certain
commercial equipment or materials are identified in this paper to
specify the experimental procedure. Such identification does not imply
recommendation or endorsement by the National Institute of Standards and
Technology, nor does it imply that the materials or equipment identified
are necessarily the best available for the purpose.
NR 56
TC 2
Z9 2
U1 0
U2 10
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0891-5849
J9 FREE RADICAL BIO MED
JI Free Radic. Biol. Med.
PD AUG 15
PY 2012
VL 53
IS 4
BP 854
EP 862
DI 10.1016/j.freeradbiomed.2012.05.044
PG 9
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA 994GY
UT WOS:000307920100022
PM 22683603
ER
PT J
AU Lok, B
Khan, S
Mutter, R
Liu, J
Fields, R
Pulitzer, M
Shi, WJ
Zhang, ZG
Kraus, D
Pfister, D
Busam, KJ
Brownell, I
Lee, N
AF Lok, Benjamin
Khan, Sabrina
Mutter, Robert
Liu, Jeffrey
Fields, Ryan
Pulitzer, Melissa
Shi, Weiji
Zhang, Zhigang
Kraus, Dennis
Pfister, David
Busam, Klaus J.
Brownell, Isaac
Lee, Nancy
TI Selective radiotherapy for the treatment of head and neck Merkel cell
carcinoma
SO CANCER
LA English
DT Article
DE Merkel cell; carcinoma; radiotherapy; recurrence; survival; head and
neck; radiation; neuroendocrine
ID LYMPH-NODE BIOPSY; SINGLE INSTITUTION; SKIN; RADIATION; EXPERIENCE;
PROGNOSIS; SURVIVAL; FEATURES; RISK
AB BACKGROUND. The role of radiotherapy (RT) in the management of Merkel cell carcinoma (MCC) is controversial. The authors of this report evaluated the rates and patterns of failure in a selected group of patients who underwent RT for MCC of the head and neck (HN). METHODS. The records of 145 consecutive patients with MCC of the HN who presented to the authors' institution between 1988 and 2009 were reviewed. Only patients who received RT at the institution were included. The cumulative incidence of locoregional failure (LRF), distant metastatic failure (DMF), disease progression (DP) and disease-specific death (DSD) were estimated with death as a competing risk. RESULTS. Forty-eight patients were identified. The median follow-up was 51 months (range, 6-220 months) for living patients. LRF developed in 5 patients (10%), and those patients had a median time to recurrence of 3 months. Two of the 5 LRFs were local and developed at the edge of the treatment field; the remaining 3 LRFs were in lymph nodes and occurred outside the treatment field. DMF developed in 12 patients (25%). The estimated 5-year cumulative incidences of LRF, DP, and DSD were 10%, 30%, and 21%, respectively. Acute toxicities included 5 episodes (10%) of grade 3 dermatitis and 1 episode (2%) of grade 3 mucositis. CONCLUSIONS. The authors report a site-specific series of patients with HN MCC who received RT. In this group of patients with adverse features, RT was well tolerated, and LRF was low. The propensity for MCC to recur at the edge of the treatment field suggests that generous margins are appropriate when RT is administered. Cancer 2012. (c) 2011 American Cancer Society.
C1 [Lok, Benjamin; Khan, Sabrina; Mutter, Robert; Lee, Nancy] Mem Sloan Kettering Canc Ctr, Dept Radiat Oncol, New York, NY 10065 USA.
[Lok, Benjamin; Khan, Sabrina; Mutter, Robert; Lee, Nancy] NYU, Sch Med, New York, NY USA.
[Liu, Jeffrey] Temple Univ, Dept Otolaryngol, Philadelphia, PA 19122 USA.
[Fields, Ryan] Mem Sloan Kettering Canc Ctr, Dept Surg, Gastr & Mixed Tumor Serv, New York, NY 10065 USA.
[Pulitzer, Melissa; Busam, Klaus J.] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10065 USA.
[Shi, Weiji; Zhang, Zhigang] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10065 USA.
[Kraus, Dennis] Mem Sloan Kettering Canc Ctr, Head & Neck Serv, Dept Surg, New York, NY 10065 USA.
[Pfister, David] Mem Sloan Kettering Canc Ctr, Head & Neck Med Oncol Serv, Dept Med, New York, NY 10065 USA.
[Brownell, Isaac] NCI, Dermatol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Lee, N (reprint author), Mem Sloan Kettering Canc Ctr, Dept Radiat Oncol, 1275 York Ave, New York, NY 10065 USA.
EM leen2@mskcc.org
NR 24
TC 7
Z9 7
U1 1
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0008-543X
J9 CANCER-AM CANCER SOC
JI Cancer
PD AUG 15
PY 2012
VL 118
IS 16
BP 3937
EP 3944
DI 10.1002/cncr.26738
PG 8
WC Oncology
SC Oncology
GA 983JZ
UT WOS:000307116900011
PM 22180314
ER
PT J
AU Prickett, TD
Samuels, Y
AF Prickett, Todd D.
Samuels, Yardena
TI Molecular Pathways: Dysregulated Glutamatergic Signaling Pathways in
Cancer
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID PROTEIN-COUPLED RECEPTORS; METASTATIC MELANOMA; NMDA RECEPTORS;
GLIOMA-CELLS; IN-VIVO; METABOTROPIC GLUTAMATE-RECEPTOR-1;
PHARMACOLOGICAL BLOCKADE; THERAPEUTIC TARGET; HUMAN MELANOCYTES; BRAF
INHIBITORS
AB The neurotransmitter glutamate interacts with glutamate receptor proteins, leading to the activation of multiple signaling pathways. Dysfunction in the glutamatergic signaling pathway is well established as a frequent player in diseases such as schizophrenia, Alzheimer disease, and brain tumors (gliomas). Recently, aberrant functioning of this pathway has also been shown in melanoma. In both glioma and melanoma, glutamate secretion stimulates tumor growth, proliferation, and survival through activation of the mitogen-activated protein kinase and phosphoinositide 3-kinase/Akt pathways. In the future, extracellular glutamate levels and glutamatergic signaling may serve as biological markers for tumorigenicity and facilitate targeted therapy for melanoma. Clin Cancer Res; 18(16); 4240-6. (C) 2012 AACR.
C1 [Prickett, Todd D.; Samuels, Yardena] NHGRI, NIH, Bethesda, MD 20892 USA.
RP Samuels, Y (reprint author), NHGRI, NIH, Bldg 50,Room 5140,50 South Dr,MSC 8000, Bethesda, MD 20892 USA.
EM samuelsy@mail.nih.gov
FU National Human Genome Research Institute, National Institutes of Health
FX Intramural Research Program, National Human Genome Research Institute,
National Institutes of Health.
NR 64
TC 34
Z9 34
U1 2
U2 6
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 2012
VL 18
IS 16
BP 4240
EP 4246
DI 10.1158/1078-0432.CCR-11-1217
PG 7
WC Oncology
SC Oncology
GA 988PY
UT WOS:000307504200005
PM 22648273
ER
PT J
AU Bates, SE
AF Bates, Susan E.
TI Pancreatic Cancer: Steps in the Right Direction
SO CLINICAL CANCER RESEARCH
LA English
DT Editorial Material
C1 NCI, Bethesda, MD 20892 USA.
RP Bates, SE (reprint author), NCI, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
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
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD AUG 15
PY 2012
VL 18
IS 16
BP 4248
EP 4248
DI 10.1158/1078-0432.CCR-12-2162
PG 1
WC Oncology
SC Oncology
GA 988PY
UT WOS:000307504200006
PM 22896690
ER
PT J
AU Wei, CJ
Yassine, HM
McTamney, PM
Gall, JGD
Whittle, JRR
Boyington, JC
Nabel, GJ
AF Wei, Chih-Jen
Yassine, Hadi M.
McTamney, Patrick M.
Gall, Jason G. D.
Whittle, James R. R.
Boyington, Jeffrey C.
Nabel, Gary J.
TI Elicitation of Broadly Neutralizing Influenza Antibodies in Animals with
Previous Influenza Exposure
SO SCIENCE TRANSLATIONAL MEDICINE
LA English
DT Article
ID MONOCLONAL-ANTIBODIES; PROTECTIVE IMMUNITY; A VIRUSES; VACCINE;
HEMAGGLUTININS; INDUCTION; EPITOPE; CELLS
AB The immune system responds to influenza infection by producing neutralizing antibodies to the viral surface protein, hemagglutinin (HA), which regularly changes its antigenic structure. Antibodies that target the highly conserved stem region of HA neutralize diverse influenza viruses and can be elicited through vaccination in animals and humans. Efforts to develop universal influenza vaccines have focused on strategies to elicit such antibodies; however, the concern has been raised that previous influenza immunity may abrogate the induction of such broadly protective antibodies. We show here that prime-boost immunization can induce broadly neutralizing antibody responses in influenza-immune mice and ferrets that were previously infected or vaccinated. HA stem-directed antibodies were elicited in mice primed with a DNA vaccine and boosted with inactivated vaccine from H1N1 A/New Caledonia/20/1999 (1999 NC) HA regardless of preexposure. Similarly, gene-based vaccination with replication-defective adenovirus 28 (rAd28) and 5 (rAd5) vectors encoding 1999 NC HA elicited stem-directed neutralizing antibodies and conferred protection against unmatched 1934 and 2007 H1N1 virus challenge in influenza-immune ferrets. Indeed, previous exposure to certain strains could enhance immunogenicity: The strongest HA stem-directed immune response was observed in ferrets previously infected with a divergent 1934 H1N1 virus. These findings suggest that broadly neutralizing antibodies against the conserved stem region of HA can be elicited through vaccination despite previous influenza exposure, which supports the feasibility of developing stem-directed universal influenza vaccines for humans.
C1 [Wei, Chih-Jen; Yassine, Hadi M.; McTamney, Patrick M.; Whittle, James R. R.; Boyington, Jeffrey C.; Nabel, Gary J.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Gall, Jason G. D.] GenVec Inc, Gaithersburg, MD 20878 USA.
RP Nabel, GJ (reprint author), NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
EM gnabel@nih.gov
FU Intramural Research Program of the VRC, National Institute of Allergy
and Infectious Diseases (NIAID), NIH
FX This research was supported by the Intramural Research Program of the
VRC, National Institute of Allergy and Infectious Diseases (NIAID), NIH.
The findings and conclusions in this report are those of the authors and
do not necessarily reflect the views of the funding agency.
NR 21
TC 29
Z9 30
U1 0
U2 8
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 1946-6234
J9 SCI TRANSL MED
JI Sci. Transl. Med.
PD AUG 15
PY 2012
VL 4
IS 147
AR 147ra114
DI 10.1126/scitranslmed.3004273
PG 8
WC Cell Biology; Medicine, Research & Experimental
SC Cell Biology; Research & Experimental Medicine
GA 994UR
UT WOS:000307958800010
PM 22896678
ER
PT J
AU Oh, S
Schwartz, RH
Singh, NJ
AF Oh, Soyoung
Schwartz, Ronald H.
Singh, Nevil J.
TI Development and Tolerization of Hyperacute Rejection in a Transgenic
Mouse Graft Versus Host Model
SO TRANSPLANTATION
LA English
DT Article
DE Hyperacute rejection; Tolerance; Cellular therapy; B-cell tolerance;
T-cell activation
ID XENOGRAFT REJECTION; T-CELLS; IN-VIVO; B-CELLS; TOLERANCE;
XENOTRANSPLANTATION; ANTIBODY; PREVENTION; INDUCTION; BARRIERS
AB Background. The hyperacute rejection mediated by preexisting antibodies is a major impediment to the success of transplants across allogeneic and xenogeneic barriers. We report a new mouse model that allows us to not only monitor the sensitization of B cells mediating the hyperacute response but also validate therapeutic strategies for tolerizing them.
Model. The new model system uses 5C.C7,RAG2(-/-) T-cell receptor transgenic T cells and B10.S(9R),CD3 epsilon(-/-) hosts for adoptive transfer experiments.
Results and Conclusions. In the allogeneic hosts, transgenic T cells expanded briefly before being chronically deleted. Once the deletion was initiated, a second graft of donor cells was used to assess a hyperacute response. The rapid rejection of the second cohort correlated with the appearance of donor-specific antibodies in the serum. Interestingly, chronically stimulated T cells were relatively resistant to hyperacute rejection, suggesting an explanation for the slower rejection kinetics of the first cohort even as the second cohort of identical donor cells was being hyperacutely rejected. Finally, we could tolerize the potential for a hyperacute response, by pretreating recipients with a single infusion of naive donor B cells before the first T-cell transfer. This treatment not only abrogated the development of a hyperacute response but also allowed the primary graft to survive in vivo for extended periods.
C1 [Schwartz, Ronald H.; Singh, Nevil J.] NIAID, Lab Cellular & Mol Immunol, NIH, Bethesda, MD 20892 USA.
[Oh, Soyoung] Mem Sloan Kettering Canc Ctr, Program Immunol, New York, NY USA.
RP Singh, NJ (reprint author), NIAID, Lab Cellular & Mol Immunol, NIH, Bldg 4,Room 211,4 Ctr Dr, Bethesda, MD 20892 USA.
EM nevil@helix.nih.gov
FU National Institute of Allergy and Infectious Diseases, National
Institutes of Health
FX This research was supported by the Intramural Research Program of the
National Institute of Allergy and Infectious Diseases, National
Institutes of Health.
NR 22
TC 1
Z9 1
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0041-1337
J9 TRANSPLANTATION
JI Transplantation
PD AUG 15
PY 2012
VL 94
IS 3
BP 234
EP 240
DI 10.1097/TP.0b013e31825ccb91
PG 7
WC Immunology; Surgery; Transplantation
SC Immunology; Surgery; Transplantation
GA 988MN
UT WOS:000307495200005
PM 22797707
ER
PT J
AU Desai, AA
Zhou, T
Ahmad, H
Zhang, W
Mu, WB
Trevino, S
Wade, MS
Raghavachari, N
Kato, GJ
Peters-Lawrence, MH
Thiruvoipati, T
Turner, K
Artz, N
Huang, Y
Patel, AR
Yuan, JXJ
Gordeuk, VR
Lang, RM
Garcia, JGN
Machado, RF
AF Desai, Ankit A.
Zhou, Tong
Ahmad, Homaa
Zhang, Wei
Mu, Wenbo
Trevino, Sharon
Wade, Michael S.
Raghavachari, Nalini
Kato, Gregory J.
Peters-Lawrence, Marlene H.
Thiruvoipati, Tejas
Turner, Kristin
Artz, Nicole
Huang, Yong
Patel, Amit R.
Yuan, Jason X. -J.
Gordeuk, Victor R.
Lang, Roberto M.
Garcia, Joe G. N.
Machado, Roberto F.
TI A Novel Molecular Signature for Elevated Tricuspid Regurgitation
Velocity in Sickle Cell Disease
SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
LA English
DT Article
DE microarray; candidate gene approach; eQTL; pulmonary hypertension
ID PULMONARY ARTERIAL-HYPERTENSION; POLYPEPTIDE
N-ACETYLGALACTOSAMINYLTRANSFERASE; ENDOTHELIAL-CELLS; EXPRESSION; RISK;
IDENTIFICATION; POLYMORPHISMS; VASODILATION; HEMOGLOBIN; PRECURSORS
AB Rationale: An increased tricuspid regurgitation jet velocity (TRV > 2.5 m/s) and pulmonary hypertension defined by right heart catheterization both independently confer increased mortality in sickle cell disease (SCD). Objectives: We explored the usefulness of peripheral blood mononuclear cell-derived gene signatures as biomarkers for an elevated TRV in SCD.
Methods: Twenty-seven patients with SCD underwent echocardiography and peripheral blood mononuclear cell isolation for expression profiling and 112 patients with SCD were genotyped for single-nucleotide polymorphisms.
Measurements and Main Results: Genome-wide gene and miRNA expression profiles were correlated against TRV, yielding 631 transcripts and 12 miRNAs. Support vector machine analysis identified a 10-gene signature including GALNT13 (encoding polypeptide N-acetylgalactosaminyltransferase 13) that discriminates patients with and without increased TRV with 100% accuracy. This finding was then validated in a cohort of patients with SCD without (n = 10) and with pulmonary hypertension (n = 10,90% accuracy). Increased TRV-related miRNAs revealed strong in silica binding predictions of miR-301a to GALNT13 corroborated by microarray analyses demonstrating an inverse correlation between their expression. A genetic association study comparing patients with an elevated (n = 49) versus normal (n = 63) TRV revealed five significant single-nucleotide polymorphisms within GALNT13 (P < 0.005), four trans-acting (P < 2.1 x 10(-7)) and one cis-acting (P = 0.6 x 10(-4)) expression quantitative trait locus upstream of the adenosine-A2B receptor gene (ADORA2B).
Conclusions: These studies validate the clinical usefulness of genomic signatures as potential biomarkers and highlight ADORA2B and GALNT13 as potential candidate genes in SCD-associated elevated TRV.
C1 [Machado, Roberto F.] Univ Illinois, Inst Personalized Resp Med, Sect Pulm Crit Care Med Sleep & Allergy, Chicago, IL 60612 USA.
[Desai, Ankit A.] Univ Illinois, Cardiol Sect, Chicago, IL 60612 USA.
[Zhang, Wei; Mu, Wenbo] Univ Illinois, Dept Pediat, Inst Human Genet, Ctr Canc, Chicago, IL 60612 USA.
[Gordeuk, Victor R.] Univ Illinois, Dept Med, Ctr Comprehens Sickle Cell, Chicago, IL 60612 USA.
[Ahmad, Homaa; Thiruvoipati, Tejas; Huang, Yong; Patel, Amit R.; Lang, Roberto M.] Univ Chicago, Dept Med, Chicago, IL 60637 USA.
[Raghavachari, Nalini] NHLBI, Genom Core Facil, Genet & Dev Biol Ctr, NIH, Bethesda, MD 20892 USA.
[Kato, Gregory J.; Peters-Lawrence, Marlene H.] NHLBI, Cardiovasc & Pulm Branch, NIH, Bethesda, MD 20892 USA.
[Turner, Kristin; Artz, Nicole] Loyola Univ, Dept Med, Maywood, IL 60153 USA.
RP Machado, RF (reprint author), Univ Illinois, Inst Personalized Resp Med, Sect Pulm Crit Care Med Sleep & Allergy, 840 S Wood St,Room 920-N,Clin Sci Bldg,MC 719, Chicago, IL 60612 USA.
EM machador@uic.edu
RI Patel, Amit/B-2464-2014; Kato, Gregory/I-7615-2014
OI Patel, Amit/0000-0001-7621-6463; Kato, Gregory/0000-0003-4465-3217
FU Intramural NIH HHS [ZIA HL006013-04]; NCRR NIH HHS [UL1 RR029879,
UL1RR029879]; NHLBI NIH HHS [K23HL098454, 1-R0 HL079912-02, F32
HL090359, F32HL090359, K23 HL098454, R01 HL079912]
NR 44
TC 20
Z9 20
U1 0
U2 8
PU AMER THORACIC SOC
PI NEW YORK
PA 61 BROADWAY, FL 4, NEW YORK, NY 10006 USA
SN 1073-449X
J9 AM J RESP CRIT CARE
JI Am. J. Respir. Crit. Care Med.
PD AUG 15
PY 2012
VL 186
IS 4
BP 359
EP 368
DI 10.1164/rccm.201201-0057OC
PG 10
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA 989ZG
UT WOS:000307600200011
PM 22679008
ER
PT J
AU Rudenko, IN
Kaganovich, A
Hauser, DN
Beylina, A
Chia, R
Ding, JH
Maric, D
Jaffe, H
Cookson, MR
AF Rudenko, Iakov N.
Kaganovich, Alice
Hauser, David N.
Beylina, Aleksandra
Chia, Ruth
Ding, Jinhui
Maric, Dragan
Jaffe, Howard
Cookson, Mark R.
TI The G2385R variant of leucine-rich repeat kinase 2 associated with
Parkinson's disease is a partial loss-of-function mutation
SO BIOCHEMICAL JOURNAL
LA English
DT Article
DE gene mutation; Hsp90; inclusion body; kinase activity; neurite length;
WD40 domain
ID CYTOPLASMIC LOCALIZATION; 14-3-3 BINDING; LRRK2;
LEUCINE-RICH-REPEAT-KINASE-2; STABILITY; INHIBITION; ARGININE; MUTANT;
SUBSTITUTION; POPULATION
AB Autosomal-dominant missense mutations in LRRK2 (leucine-rich repeat kinase 2) are a common genetic cause of PD (Parkinson's disease). LRRK2 is a multidomain protein with kinase and GTPase activities. Dominant mutations are found in the domains that have these two enzyme activities, including the common G2019S mutation that increases kinase activity 2-3-fold. However, there is also a genetic variant in some populations, G2385R, that lies in a C-terminal WD40 domain of LRRK2 and acts as a risk factor for PD. In the present study we show that the G2385R mutation causes a partial loss of the kinase function of LRRK2 and deletion of the C-terminus completely abolishes kinase activity. This effect is strong enough to overcome the kinase-activating effects of the G2019S mutation in the kinase domain. Hsp90 (heat-shock protein of 90 kDa) has an increased affinity for the G2385R variant compared with WT (wild-type) LRRK2, and inhibition of the chaperone binding combined with proteasome inhibition leads to association of mutant LRRK2 with high molecular mass native fractions that probably represent proteasome degradation pathways. The loss-of-function of G2385R correlates with several cellular phenotypes that have been proposed to be kinase-dependent. These results suggest that the C-terminus of LRRK2 plays an important role in maintaining enzymatic function of the protein and that G2385R may be associated with PD in a way that is different from kinase-activating mutations. These results may be important in understanding the differing mechanism(s) by which mutations in LRRK2 act and may also have implications for therapeutic strategies for PD.
C1 [Rudenko, Iakov N.; Kaganovich, Alice; Hauser, David N.; Beylina, Aleksandra; Chia, Ruth; Cookson, Mark R.] NIA, Cell Biol & Gene Express Sect, NIH, Bethesda, MD 20892 USA.
[Hauser, David N.] Brown Univ, Natl Inst Hlth Grad Partnership Program, Dept Neurosci, Providence, RI 02912 USA.
[Ding, Jinhui] NIA, Bioinformat Facil, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
[Maric, Dragan] Natl Inst Neurol Disorders & Stroke, Flow Cytometry Core Facil, NIH, Bethesda, MD 20892 USA.
[Jaffe, Howard] Natl Inst Neurol Disorders & Stroke, Peptide Sequencing Facil, NIH, Bethesda, MD 20892 USA.
RP Cookson, MR (reprint author), NIA, Cell Biol & Gene Express Sect, NIH, Bethesda, MD 20892 USA.
EM cookson@mail.nih.gov
RI Hauser, David/I-4933-2012
OI Hauser, David/0000-0002-9500-5255
FU NIH, National Institute on Aging [AG000948]; National Institute of
Neurological Diseases and Stroke
FX This research was supported in part by the Intramural Research Program
of the NIH, National Institute on Aging [project number AG000948] and by
the National Institute of Neurological Diseases and Stroke.
NR 38
TC 41
Z9 41
U1 2
U2 5
PU PORTLAND PRESS LTD
PI LONDON
PA THIRD FLOOR, EAGLE HOUSE, 16 PROCTER STREET, LONDON WC1V 6 NX, ENGLAND
SN 0264-6021
J9 BIOCHEM J
JI Biochem. J.
PD AUG 15
PY 2012
VL 446
BP 99
EP 111
DI 10.1042/BJ20120637
PN 1
PG 13
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 990JH
UT WOS:000307626300010
PM 22612223
ER
PT J
AU Zarate, CA
Brutsche, N
Laje, G
Luckenbaugh, DA
Venkata, SLV
Ramamoorthy, A
Moaddel, R
Wainer, IW
AF Zarate, Carlos A., Jr.
Brutsche, Nancy
Laje, Gonzalo
Luckenbaugh, David A.
Venkata, Swarajya L. Vattem
Ramamoorthy, Anuradha
Moaddel, Ruin
Wainer, Irving W.
TI Relationship of Ketamine's Plasma Metabolites with Response, Diagnosis,
and Side Effects in Major Depression
SO BIOLOGICAL PSYCHIATRY
LA English
DT Article
DE Bipolar disorder; dehydronorketamine; depression; hydroxynorketamine;
norketamine; psychosis; response
ID D-ASPARTATE ANTAGONIST; RAPID ANTIDEPRESSANT RESPONSE; HUMAN
LIVER-MICROSOMES; COMPARATIVE PHARMACOLOGY; CYTOCHROME-P450 ENZYMES;
HEALTHY-VOLUNTEERS; DRUG-METABOLISM; N-DEMETHYLATION; IN-VITRO;
NORKETAMINE
AB Background: Ketamine has rapid antidepressant effects lasting as long as 1 week in patients with major depressive disorder (MDD) and bipolar depression (BD). Ketamine is extensively metabolized. This study examined the relationship between ketamine metabolites and response, diagnosis, and psychotomimetic symptoms in MDD and BD patients.
Methods: Following a 40-minute ketamine infusion (.5 mg/kg), plasma samples were collected at 40, 80, 110, and 230 minutes and day 1 postinfusion in 67 patients currently experiencing a major depressive episode (MDD, n = 45; BD, n = 22). Concentrations of ketamine, norketamine (NK), dehydronorketamine (DHNK), six hydroxynorketamine metabolites (HNK), and hydroxyketamine (HK) were measured. Plasma concentrations were analyzed by diagnostic group and correlated with patients' depressive, psychotic, and dissociative symptoms. The relationship between cytochrome P450 gene polymorphisms and metabolites, response, and diagnosis was also examined.
Results: Ketamine, NK, DHNK, four of six HNKs, and HK were present during the first 230 minutes postinfusion. Patients with BD had higher plasma concentrations of DHNK, (2S,6S;2R,6R)-HNK, (2S,6R;2R,6S)-HNK, and (2S,5S;2R,5R)-HNK than patients with MDD, who, in turn, had higher concentrations of (2S,6S;2R,6R)-HK. Higher (2S,5S;2R,5R)-HNK concentrations were associated with nonresponse to ketamine in BD patients. Dehydronorketamine, HNK4c, and HNK4f levels were significantly negatively correlated with psychotic and dissociative symptoms at 40 minutes. No relationship was found between cytochrome P450 genes and any of the parameters examined.
Conclusions: A diagnostic difference was observed in the metabolism and disposition of ketamine. Concentrations of (2S,5S;2R,5R)-HNK were related to nonresponse to ketamine in BD. Some hydroxylated metabolites of ketamine correlated with psychotic and dissociative symptoms.
C1 [Zarate, Carlos A., Jr.; Brutsche, Nancy; Luckenbaugh, David A.] NIMH, NIH, Div Intramural Res Programs, Expt Therapeut & Pathophysiol Branch,CRC, Bethesda, MD 20892 USA.
[Laje, Gonzalo] NIMH, Human Genet Branch, NIH, Bethesda, MD 20892 USA.
[Laje, Gonzalo] NIMH, Genet Basis Mood & Anxiety Disorders Sect, NIH, Bethesda, MD 20892 USA.
[Venkata, Swarajya L. Vattem; Ramamoorthy, Anuradha; Moaddel, Ruin; Wainer, Irving W.] NIA, Lab Clin Invest, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
RP Zarate, CA (reprint author), NIMH, NIH, Div Intramural Res Programs, Expt Therapeut & Pathophysiol Branch,CRC, 10 Ctr Dr,Unit 7 SE,Room 7-3445, Bethesda, MD 20892 USA.
EM zaratec@mail.nih.gov
RI Laje, Gonzalo/L-2654-2014
OI Laje, Gonzalo/0000-0003-2763-3329
FU Intramural Research Programs of the National Institute of Aging,
National Institutes of Health (NIH); National Institute of Mental
Health, NIH; NIH [MH085098-01]; Brain & Behavior Research Foundation
Bipolar Disorders Award
FX This work was supported by the Intramural Research Programs of the
National Institute of Aging, National Institutes of Health (NIH), and
the National Institute of Mental Health, NIH, as well as NIH Grant
MH085098-01 to GL, and the Brain & Behavior Research Foundation Bipolar
Disorders Award (CAZ).
NR 42
TC 63
Z9 63
U1 1
U2 20
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0006-3223
J9 BIOL PSYCHIAT
JI Biol. Psychiatry
PD AUG 15
PY 2012
VL 72
IS 4
BP 331
EP 338
DI 10.1016/j.biopsych.2012.03.004
PG 8
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 980NA
UT WOS:000306898800018
PM 22516044
ER
PT J
AU Shatz, M
Menendez, D
Resnick, MA
AF Shatz, Maria
Menendez, Daniel
Resnick, Michael A.
TI The Human TLR Innate Immune Gene Family Is Differentially Influenced by
DNA Stress and p53 Status in Cancer Cells
SO CANCER RESEARCH
LA English
DT Article
ID TOLL-LIKE RECEPTORS; HUMAN-DISEASE; EXPRESSION; ACTIVATION; AGONISTS;
CHEMOTHERAPY; MUTATIONS; INDUCTION; APOPTOSIS; THERAPY
AB The transcription factor p53 regulates genes associated with a wide range of functions, including the Toll-like receptor (TLR) set of innate immunity genes, suggesting that p53 also modulates the human immune response. The TLR family comprises membrane glycoproteins that recognize pathogen-associated molecular patterns (PAMP) and mediate innate immune responses, and TLR agonists are being used as adjuvants in cancer treatments. Here, we show that doxorubicin, 5-fluorouracil, and UV and ionizing radiation elicit changes in TLR expression that are cell line-and damage-specific. Specifically, treatment-induced expression changes led to increased downstream cytokine expression in response to ligand stimulation. The effect of DNA stressors on TLR expression was mainly mediated by p53, and several p53 cancer-associated mutants dramatically altered the pattern of TLR gene expression. In all cell lines tested, TLR3 induction was p53-dependent, whereas induction of TLR9, the most stress-responsive family member, was less dependent on status of p53. In addition, each of the 10 members of the innate immune TLR gene family tested was differentially inducible. Our findings therefore show that the matrix of p53 status, chromosome stress, and responsiveness of individual TLRs should be considered in TLR-based cancer therapies. Cancer Res; 72(16); 3948-57. (C) 2012 AACR.
C1 [Shatz, Maria; Menendez, Daniel; Resnick, Michael A.] NIEHS, NIH, Chromosome Stabil Grp, Mol Genet Lab, Res Triangle Pk, NC 27709 USA.
RP Resnick, MA (reprint author), NIEHS, NIH, Chromosome Stabil Grp, Mol Genet Lab, POB 12233, Res Triangle Pk, NC 27709 USA.
EM resnick@niehs.nih.gov
FU NIEHS [Z01-ES065079]
FX The study was supported by NIEHS intramural research funds, project
Z01-ES065079.
NR 45
TC 39
Z9 41
U1 0
U2 2
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
J9 CANCER RES
JI Cancer Res.
PD AUG 15
PY 2012
VL 72
IS 16
BP 3948
EP 3957
DI 10.1158/0008-5472.CAN-11-4134
PG 10
WC Oncology
SC Oncology
GA 993SY
UT WOS:000307881100008
PM 22673234
ER
PT J
AU Wu, J
Li, JQ
Salcedo, R
Mivechi, NF
Trinchieri, G
Horuzsko, A
AF Wu, Juan
Li, Jiaqi
Salcedo, Rosalba
Mivechi, Nahid F.
Trinchieri, Giorgio
Horuzsko, Anatolij
TI The Proinflammatory Myeloid Cell Receptor TREM-1 Controls Kupffer Cell
Activation and Development of Hepatocellular Carcinoma
SO CANCER RESEARCH
LA English
DT Article
ID NF-KAPPA-B; CHEMICAL HEPATOCARCINOGENESIS; FUNCTIONAL GENOMICS; CANCER
DEVELOPMENT; INFLAMMATION; MACROPHAGES; PROLIFERATION; PROGRESSION;
EXPRESSION; ENDOTOXIN
AB Chronic inflammation drives liver cancer pathogenesis, invasion, and metastasis. Liver Kupffer cells have crucial roles in mediating the inflammatory processes that promote liver cancer, but the mechanistic basis for their contributions are not fully understood. Here we show that expression of the proinflammatory myeloid cell surface receptor TREM-1 expressed by Kupffer cells is a crucial factor in the development and progression of liver cancer. Deletion of the murine homolog Trem1 in mice attenuated hepatocellular carcinogenesis triggered by diethylnitrosamine (DEN). Trem1 deficiency attenuated Kupffer cell activation by downregulating transcription and protein expression of interleukin (IL)-6, IL-1 beta, TNF, CCL2, and CXCL10. In addition, Trem1 ablation diminished activation of the p38, extracellular regulated kinase 1/2, JNK, mitogen-activated protein kinase, and NF-kappa B signaling pathways in Kupffer cells, resulting in diminished liver injury after DEN exposure. Adoptive transfer of wild-type Kupffer cells to Trem1-deficient mice complemented these defects and reversed unresponsiveness to DEN-induced liver injury and malignant development. Together, our findings offer causal evidence that TREM-1 is a pivotal determinant of Kupffer cell activation in liver carcinogenesis, deepening mechanistic insights into how chronic inflammation underpins the development and progression of liver cancer. Cancer Res; 72(16); 3977-86. (C) 2012 AACR.
C1 [Wu, Juan; Li, Jiaqi; Mivechi, Nahid F.; Horuzsko, Anatolij] Georgia Hlth Sci Univ, Ctr Mol Chaperone Radiobiol & Canc Virol, Dept Med, Augusta, GA 30912 USA.
[Salcedo, Rosalba; Trinchieri, Giorgio] NCI, Canc & Inflammat Program, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Salcedo, Rosalba] SAIC Frederick Inc, Frederick, MD USA.
RP Horuzsko, A (reprint author), Georgia Hlth Sci Univ, Ctr Mol Chaperone Radiobiol & Canc Virol, Dept Med, 1410 Laney Walker Blvd, Augusta, GA 30912 USA.
EM ahoruzsko@georgiahealth.edu
FU National Institutes of Health [AI055923, CA062130, CA132640]
FX This work was supported by the National Institutes of Health grants
AI055923 (A. Horuzsko) and CA062130 and CA132640 (N.F. Mivechi).
NR 35
TC 57
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U1 1
U2 6
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
J9 CANCER RES
JI Cancer Res.
PD AUG 15
PY 2012
VL 72
IS 16
BP 3977
EP 3986
DI 10.1158/0008-5472.CAN-12-0938
PG 10
WC Oncology
SC Oncology
GA 993SY
UT WOS:000307881100011
PM 22719066
ER
PT J
AU Yaqoob, U
Cao, S
Shergill, U
Jagavelu, K
Geng, ZM
Yin, M
de Assuncao, TM
Cao, Y
Szabolcs, A
Thorgeirsson, S
Schwartz, M
Yang, JD
Ehman, R
Roberts, L
Mukhopadhyay, D
Shah, VH
AF Yaqoob, Usman
Cao, Sheng
Shergill, Uday
Jagavelu, Kumaravelu
Geng, Zhimin
Yin, Meng
de Assuncao, Thiago M.
Cao, Ying
Szabolcs, Anna
Thorgeirsson, Snorri
Schwartz, Martin
Yang, Ju Dong
Ehman, Richard
Roberts, Lewis
Mukhopadhyay, Debabrata
Shah, Vijay H.
TI Neuropilin-1 Stimulates Tumor Growth by Increasing Fibronectin Fibril
Assembly in the Tumor Microenvironment
SO CANCER RESEARCH
LA English
DT Article
ID DOMAIN-CONTAINING PROTEIN; ENDOTHELIAL-CELLS; PROGENITOR CELLS; HUMAN
GLIOMA; ACTIVATION; MATRIX; INTERACTS; CANCER; BETA; VEGF
AB The tumor microenvironment, including stromal myofibroblasts and associated matrix proteins, regulates cancer cell invasion and proliferation. Here, we report that neuropilin-1 (NRP-1) orchestrates communications between myofibroblasts and soluble fibronectin that promote alpha 5 beta 1 integrin-dependent fibronectin fibril assembly, matrix stiffness, and tumor growth. Tumor growth and fibronectin fibril assembly were reduced by genetic depletion or antibody neutralization of NRP-1 from stromal myofibroblasts in vivo. Mechanistically, the increase in fibronectin fibril assembly required glycosylation of serine 612 of the extracellular domain of NRP-1, an intact intracellular NRP-1 SEA domain, and intracellular associations between NRP-1, the scaffold protein GIPC, and the nonreceptor tyrosine kinase c-Abl that augmented alpha 5 beta 1 fibronectin fibril assembly activity. Analysis of human cancer specimens established an association between tumoral NRP-1 levels and clinical outcome. Our findings indicate that NRP-1 activates the tumor microenvironment, thereby promoting tumor growth. These results not only identify new molecular mechanisms of fibronectin fibril assembly but also have important implications for therapeutic targeting of the myofibroblast in the tumor microenvironment. Cancer Res; 72(16); 4047-59. (C) 2012 AACR.
C1 [Yaqoob, Usman; Cao, Sheng; Shergill, Uday; Jagavelu, Kumaravelu; Geng, Zhimin; de Assuncao, Thiago M.; Yang, Ju Dong; Roberts, Lewis; Shah, Vijay H.] Mayo Clin, Gastroenterol Res Unit, Rochester, MN 55905 USA.
[Yaqoob, Usman; Cao, Sheng; Shergill, Uday; Jagavelu, Kumaravelu; Geng, Zhimin; de Assuncao, Thiago M.; Yang, Ju Dong; Roberts, Lewis; Shah, Vijay H.] Mayo Clin, Dept Internal Med, Rochester, MN 55905 USA.
[Cao, Ying; Szabolcs, Anna; Mukhopadhyay, Debabrata] Mayo Clin, Dept Biochem & Mol Biol, Rochester, MN 55905 USA.
[Yin, Meng; Ehman, Richard] Mayo Clin, Dept Radiol, Rochester, MN 55905 USA.
[Thorgeirsson, Snorri] NCI, Bethesda, MD 20892 USA.
[Schwartz, Martin] Yale Univ, Div Cardiol, New Haven, CT USA.
[Schwartz, Martin] Yale Univ, Dept Cell Biol, New Haven, CT USA.
RP Shah, VH (reprint author), Mayo Clin, Gastroenterol Res Unit, 200 1st ST SW, Rochester, MN 55905 USA.
EM cao.sheng@mayo.edu; shah.vijay@mayo.edu
OI Yin, Meng/0000-0001-6778-192X; Roberts, Lewis/0000-0001-7885-8574
FU NIH [R01 DK 59615, R01 AA 021171, R01 HL 86990, P30 DK 084567]
FX This work was supported by the grants from NIH R01 DK 59615 R01 AA
021171, and R01 HL 86990 (V. H. Shah), P30 DK 084567-Clinical Core and
Cell Biology Core.
NR 50
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U1 0
U2 10
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
J9 CANCER RES
JI Cancer Res.
PD AUG 15
PY 2012
VL 72
IS 16
BP 4047
EP 4059
DI 10.1158/0008-5472.CAN-11-3907
PG 13
WC Oncology
SC Oncology
GA 993SY
UT WOS:000307881100018
PM 22738912
ER
PT J
AU Szabova, L
Yin, CY
Bupp, S
Guerin, TM
Schlomer, JJ
Householder, DB
Baran, ML
Yi, M
Song, YR
Sun, WP
McDunn, JE
Martin, PL
Van Dyke, T
Difilippantonio, S
AF Szabova, Ludmila
Yin, Chaoying
Bupp, Sujata
Guerin, Theresa M.
Schlomer, Jerome J.
Householder, Deborah B.
Baran, Maureen L.
Yi, Ming
Song, Yurong
Sun, Wenping
McDunn, Jonathan E.
Martin, Philip L.
Van Dyke, Terry
Difilippantonio, Simone
TI Perturbation of Rb, p53, and Brca1 or Brca2 Cooperate in Inducing
Metastatic Serous Epithelial Ovarian Cancer
SO CANCER RESEARCH
LA English
DT Article
ID FALLOPIAN-TUBE; MOUSE MODEL; CONDITIONAL INACTIVATION; PERITONEAL
MESOTHELIOMA; PAPILLARY CARCINOMA; SURFACE EPITHELIUM; DISTANT
METASTASES; MUTATIONS; MICE; INDUCTION
AB The majority of human high-grade serous epithelial ovarian cancer (SEOC) is characterized by frequent mutations in p53 and alterations in the RB and FOXM1 pathways. A subset of human SEOC harbors a combination of germline and somatic mutations as well as epigenetic dysfunction for BRCA1/2. Using Cre-conditional alleles and intrabursal induction by Cre-expressing adenovirus in genetically engineered mice, we analyzed the roles of pathway perturbations in epithelial ovarian cancer initiation and progression. Inactivation of RB-mediated tumor suppression induced surface epithelial proliferation with progression to stage I carcinoma. Additional biallelic inactivation and/or missense p53 mutation in the presence or absence of Brca1/2 caused progression to stage IV disease. As in human SEOC, mice developed peritoneal carcinomatosis, ascites, and distant metastases. Unbiased gene expression and metabolomic profiling confirmed that Rb, p53, and Brca1/2-triple mutant tumors aligned with human SEOC, and not with other intraperitoneal cancers. Together, our findings provide a novel resource for evaluating disease etiology and biomarkers, therapeutic evaluation, and improved imaging strategies in epithelial ovarian cancer. Cancer Res; 72(16); 4141-53. (C) 2012 AACR.
C1 [Szabova, Ludmila; Bupp, Sujata; Guerin, Theresa M.; Schlomer, Jerome J.; Householder, Deborah B.; Baran, Maureen L.; Martin, Philip L.; Van Dyke, Terry; Difilippantonio, Simone] NCI Federick, Ctr Adv Preclin Res, SAIC, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
[Yi, Ming; Sun, Wenping] NCI Federick, Adv Biomed Comp Ctr, SAIC, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
[Song, Yurong; Van Dyke, Terry] NCI Frederick, Mouse Canc Genet Program, Frederick, MD USA.
[Yin, Chaoying; Song, Yurong; Van Dyke, Terry] Univ N Carolina, Dept Genet, Chapel Hill, NC USA.
[McDunn, Jonathan E.] Metabolon Inc, Durham, NC USA.
RP Difilippantonio, S (reprint author), NCI Federick, Ctr Adv Preclin Res, SAIC, Frederick Natl Lab Canc Res, 1050 Boyles St,Bldg 539,Room 229, Frederick, MD 21702 USA.
EM difilips@mail.nih.gov
OI McDunn, Jonathan/0000-0001-8792-828X
FU National Cancer Institute, Intramural Research Program, NIH
[HHSN261200800001E]
FX This research was supported with federal funds from the National Cancer
Institute, Intramural Research Program, NIH under contract no.
HHSN261200800001E.
NR 49
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U1 0
U2 8
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
J9 CANCER RES
JI Cancer Res.
PD AUG 15
PY 2012
VL 72
IS 16
BP 4141
EP 4153
DI 10.1158/0008-5472.CAN-11-3834
PG 13
WC Oncology
SC Oncology
GA 993SY
UT WOS:000307881100026
PM 22617326
ER
PT J
AU Zhang, M
Mathur, A
Zhang, YW
Xi, SC
Atay, S
Hong, JA
Datrice, N
Upham, T
Kemp, CD
Ripley, RT
Wiegand, G
Avital, I
Fetsch, P
Mani, H
Zlott, D
Robey, R
Bates, SE
Li, XM
Rao, M
Schrump, DS
AF Zhang, Mary
Mathur, Aarti
Zhang, Yuwei
Xi, Sichuan
Atay, Scott
Hong, Julie A.
Datrice, Nicole
Upham, Trevor
Kemp, Clinton D.
Ripley, R. Taylor
Wiegand, Gordon
Avital, Itzak
Fetsch, Patricia
Mani, Haresh
Zlott, Daniel
Robey, Robert
Bates, Susan E.
Li, Xinmin
Rao, Mahadev
Schrump, David S.
TI Mithramycin Represses Basal and Cigarette Smoke-Induced Expression of
ABCG2 and Inhibits Stem Cell Signaling in Lung and Esophageal Cancer
Cells
SO CANCER RESEARCH
LA English
DT Article
ID ARYL-HYDROCARBON RECEPTOR; SIDE POPULATION CELLS; TRANSCRIPTION FACTOR;
ANTITUMOR-ACTIVITY; PROGNOSTIC-FACTOR; MAJOR MORBIDITY; CARCINOMA CELLS;
BCRP/ABCG2; MORTALITY; BINDING
AB Cigarette smoking at diagnosis or during therapy correlates with poor outcome in patients with lung and esophageal cancers, yet the underlying mechanisms remain unknown. In this study, we observed that exposure of esophageal cancer cells to cigarette smoke condensate (CSC) led to upregulation of the xenobiotic pump ABCG2, which is expressed in cancer stem cells and confers treatment resistance in lung and esophageal carcinomas. Furthermore, CSC increased the side population of lung cancer cells containing cancer stem cells. Upregulation of ABCG2 coincided with increased occupancy of aryl hydrocarbon receptor, Sp1, and Nrf2 within the ABCG2 promoter, and deletion of xenobiotic response elements and/or Sp1 sites markedly attenuated ABCG2 induction. Under conditions potentially achievable in clinical settings, mithramycin diminished basal as well as CSC-mediated increases in AhR, Sp1, and Nrf2 levels within the ABCG2 promoter, markedly downregulated ABCG2, and inhibited proliferation and tumorigenicity of lung and esophageal cancer cells. Microarray analyses revealed that mithramycin targeted multiple stem cell-related pathways in vitro and in vivo. Collectively, our findings provide a potential mechanistic link between smoking status and outcome of patients with lung and esophageal cancers, and support clinical use of mithramycin for repressing ABCG2 and inhibiting stem cell signaling in thoracic malignancies. Cancer Res; 72(16); 4178-92. (C) 2012 AACR.
C1 [Zhang, Mary; Mathur, Aarti; Zhang, Yuwei; Xi, Sichuan; Atay, Scott; Hong, Julie A.; Datrice, Nicole; Upham, Trevor; Kemp, Clinton D.; Ripley, R. Taylor; Rao, Mahadev; Schrump, David S.] NCI, Thorac Oncol Sect, Surg Branch, Bethesda, MD 20892 USA.
[Wiegand, Gordon; Avital, Itzak] NCI, Gastrointestinal & Hepatobiliary Malignancies Sec, Surg Branch, Bethesda, MD 20892 USA.
[Fetsch, Patricia] NCI, Pathol Lab, Bethesda, MD 20892 USA.
[Zlott, Daniel] NCI, Dept Clin Pharm, Bethesda, MD 20892 USA.
[Robey, Robert; Bates, Susan E.] NCI, Expt Therapeut Sect, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Mani, Haresh] Penn State Hershey, Med Ctr, Dept Pathol, Hershey, PA USA.
[Li, Xinmin] Univ Calif Los Angeles, Clin Microarray Core, Los Angeles, CA USA.
RP Schrump, DS (reprint author), NCI, Thorac Oncol Sect, Surg Branch, Bldg 10,4-3942,10 Ctr Dr, Bethesda, MD 20892 USA.
EM David_Schrump@nih.gov
NR 50
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U1 2
U2 12
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD AUG 15
PY 2012
VL 72
IS 16
BP 4178
EP 4192
DI 10.1158/0008-5472.CAN-11-3983
PG 15
WC Oncology
SC Oncology
GA 993SY
UT WOS:000307881100029
PM 22751465
ER
PT J
AU Caceres, G
Robey, RW
Sokol, L
McGraw, KL
Clark, J
Lawrence, NJ
Sebti, SM
Wiese, M
List, AF
AF Caceres, Gisela
Robey, Robert W.
Sokol, Lubomir
McGraw, Kathy L.
Clark, Justine
Lawrence, Nicholas J.
Sebti, Said M.
Wiese, Michael
List, Alan F.
TI HG-829 Is a Potent Noncompetitive Inhibitor of the ATP-Binding Cassette
Multidrug Resistance Transporter ABCB1
SO CANCER RESEARCH
LA English
DT Article
ID ACUTE MYELOID-LEUKEMIA; P-GLYCOPROTEIN; DRUG-BINDING; PHASE-I; GROUP-B;
CANCER; REVERSAL; MODULATOR; PSC-833; AGE
AB Transmembrane drug export mediated by the ATP-binding cassette (ABC) transporter P-glycoprotein contributes to clinical resistance to antineoplastics. In this study, we identified the substituted quinoline HG-829 as a novel, noncompetitive, and potent P-glycoprotein inhibitor that overcomes in vitro and in vivo drug resistance. We found that nontoxic concentrations of HG-829 restored sensitivity to P-glycoprotein oncolytic substrates. In ABCB1-overexpressing cell lines, HG-829 significantly enhanced cytotoxicity to daunorubicin, paclitaxel, vinblastine, vincristine, and etoposide. Coadministration of HG-829 fully restored in vivo antitumor activity of daunorubicin in mice without added toxicity. Functional assays showed that HG-829 is not a Pgp substrate or competitive inhibitor of Pgp-mediated drug efflux but rather acts as a noncompetitive modulator of P-glycoprotein transport function. Taken together, our findings indicate that HG-829 is a potent, long-acting, and noncompetitive modulator of P-glycoprotein export function that may offer therapeutic promise for multidrug-resistant malignancies. Cancer Res; 72(16); 4204-13. (c) 2012 AACR.
C1 [Lawrence, Nicholas J.; Sebti, Said M.] Univ S Florida, H Lee Moffitt Canc Ctr, Drug Discovery Program, Tampa, FL 33682 USA.
[McGraw, Kathy L.] Univ S Florida, Canc Biol PhD Program, Tampa, FL USA.
[Robey, Robert W.] NIH, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Wiese, Michael] Univ Bonn, Inst Pharm, Bonn, Germany.
RP List, AF (reprint author), H Lee Moffitt Canc Ctr & Res Inst, MCC VP, 12902 Magnolia Dr, Tampa, FL 33612 USA.
EM alan.list@moffitt.org
FU Procter and Gamble
FX This work was supported by Procter and Gamble.
NR 26
TC 5
Z9 6
U1 0
U2 6
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
J9 CANCER RES
JI Cancer Res.
PD AUG 15
PY 2012
VL 72
IS 16
BP 4204
EP 4213
DI 10.1158/0008-5472.CAN-12-0743
PG 10
WC Oncology
SC Oncology
GA 993SY
UT WOS:000307881100031
PM 22761337
ER
PT J
AU Thiele, F
Cohrs, CM
Flor, A
Lisse, TS
Przemeck, GKH
Horsch, M
Schrewe, A
Gailus-Durner, V
Ivandic, B
Katus, HA
Wurst, W
Reisenberg, C
Chaney, H
Fuchs, H
Hans, W
Beckers, J
Marini, JC
de Angelis, MH
AF Thiele, Frank
Cohrs, Christian M.
Flor, Armando
Lisse, Thomas S.
Przemeck, Gerhard K. H.
Horsch, Marion
Schrewe, Anja
Gailus-Durner, Valerie
Ivandic, Boris
Katus, Hugo A.
Wurst, Wolfgang
Reisenberg, Catherine
Chaney, Hollis
Fuchs, Helmut
Hans, Wolfgang
Beckers, Johannes
Marini, Joan C.
de Angelis, Martin Hrabe
TI Cardiopulmonary dysfunction in the Osteogenesis imperfecta mouse model
Aga2 and human patients are caused by bone-independent mechanisms
SO HUMAN MOLECULAR GENETICS
LA English
DT Article
ID GENE-EXPRESSION; PULMONARY HYPOPLASIA; AORTIC DISSECTION; KAPPA-B;
COLLAGEN; DISEASE; MICE; INVOLVEMENT; FIBROBLASTS; MATRIX
AB Osteogenesis imperfecta (OI) is an inherited connective tissue disorder with skeletal dysplasia of varying severity, predominantly caused by mutations in the collagen I genes (COL1A1/COL1A2). Extraskeletal findings such as cardiac and pulmonary complications are generally considered to be significant secondary features. Aga2, a murine model for human OI, was systemically analyzed in the German Mouse Clinic by means of in vivo and in vitro examinations of the cardiopulmonary system, to identify novel mechanisms accounting for perinatal lethality. Pulmonary and, especially, cardiac fibroblast of perinatal lethal Aga2/ animals display a strong down-regulation of Col1a1 transcripts in vivo and in vitro, resulting in a loss of extracellular matrix integrity. In addition, dysregulated gene expression of Nppa, different types of collagen and Agt in heart and lung tissue support a bone-independent vicious cycle of heart dysfunction, including hypertrophy, loss of myocardial matrix integrity, pulmonary hypertension, pneumonia and hypoxia leading to death in Aga2. These murine findings are corroborated by a pediatric OI cohort study, displaying significant progressive decline in pulmonary function and restrictive pulmonary disease independent of scoliosis. Most participants show mild cardiac valvular regurgitation, independent of pulmonary and skeletal findings. Data obtained from human OI patients and the mouse model Aga2 provide novel evidence for primary effects of type I collagen mutations on the heart and lung. The findings will have potential benefits of anticipatory clinical exams and early intervention in OI patients.
C1 [Thiele, Frank; Cohrs, Christian M.; Lisse, Thomas S.; Przemeck, Gerhard K. H.; Horsch, Marion; Schrewe, Anja; Gailus-Durner, Valerie; Fuchs, Helmut; Hans, Wolfgang; Beckers, Johannes; de Angelis, Martin Hrabe] German Res Ctr Environm Hlth GmbH, Helmholtz Zentrum Munchen, Inst Expt Genet, Neuherberg, Germany.
[Flor, Armando; Reisenberg, Catherine; Marini, Joan C.] NICHHD, Bone & Extracellular Matrix Branch, NIH, Bethesda, MD 20892 USA.
[Ivandic, Boris; Katus, Hugo A.] Heidelberg Univ, Dept Med 3, Div Cardiol, Heidelberg, Germany.
[Wurst, Wolfgang] German Res Ctr Environm Hlth GmbH, Helmholtz Zentrum Munchen, Inst Dev Genet, Neuherberg, Germany.
[Wurst, Wolfgang] Tech Univ Munich, Ctr Life & Food Sci, Chair Dev Genet, Weihenstephan, Germany.
[Chaney, Hollis] Childrens Natl Med Ctr, Washington, DC 20010 USA.
[Beckers, Johannes; de Angelis, Martin Hrabe] Tech Univ Munich, Ctr Life & Food Sci, Chair Expt Genet, Weihenstephan, Germany.
RP de Angelis, MH (reprint author), German Res Ctr Environm Hlth GmbH, Helmholtz Zentrum Munchen, Inst Expt Genet, Neuherberg, Germany.
EM hrabe@helmholtz-muenchen.de
RI Przemeck, Gerhard/A-5991-2012; Cohrs, Christian/L-7336-2013; Beckers,
Johannes/K-7237-2012; Gailus-Durner, Valerie/M-7337-2014; Hrabe de
Angelis, Martin/F-5531-2012; Katus, Hugo/P-1712-2016; Fuchs,
Helmut/M-7347-2014
OI Przemeck, Gerhard/0000-0003-3730-3454; Beckers,
Johannes/0000-0001-7874-3822; Hrabe de Angelis,
Martin/0000-0002-7898-2353; Fuchs, Helmut/0000-0002-5143-2677
FU Nationales Genomforschungs-netzwerk [01GS0850, 01GS0854]; National
Institute of Child Health & Human Development Intramural Research
Program; Helmholtz Zentrum Munchen, German Research Center for
Environmental Health (GmbH)
FX This work was supported by the Nationales Genomforschungs-netzwerk
(01GS0850 to M. H. A., 01GS0854 H. A. K.). The clinical trial was
supported by funds from the National Institute of Child Health & Human
Development Intramural Research Program. Funding to pay the Open Access
publication charges for this article was provided by Helmholtz Zentrum
Munchen, German Research Center for Environmental Health (GmbH).
NR 51
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U1 0
U2 1
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0964-6906
J9 HUM MOL GENET
JI Hum. Mol. Genet.
PD AUG 15
PY 2012
VL 21
IS 16
BP 3535
EP 3545
DI 10.1093/hmg/dds183
PG 11
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA 981JX
UT WOS:000306964700002
PM 22589248
ER
PT J
AU Renvoise, B
Stadler, J
Singh, R
Bakowska, JC
Blackstone, C
AF Renvoise, Benoit
Stadler, Julia
Singh, Rajat
Bakowska, Joanna C.
Blackstone, Craig
TI Spg20-/- mice reveal multimodal functions for Troyer syndrome protein
spartin in lipid droplet maintenance, cytokinesis and BMP signaling
SO HUMAN MOLECULAR GENETICS
LA English
DT Article
ID HEREDITARY SPASTIC PARAPLEGIA; NEUROPATHY TARGET ESTERASE; UBIQUITIN
LIGASES; SYNAPTIC GROWTH; IDENTIFICATION; DISEASE; LOCALIZATION;
MECHANISMS; INTERACTS; MACHINERY
AB Hereditary spastic paraplegias (HSPs; SPG1-48) are inherited neurological disorders characterized by lower extremity spasticity and weakness. Loss-of-function mutations in the SPG20 gene encoding spartin cause autosomal recessive Troyer syndrome (SPG20), which has additional features of short stature, cognitive deficits and distal amyotrophy. To identify cellular impairments underlying Troyer syndrome, we generated Spg20/ mice, which exhibit progressive gait defects. Although gross central nervous system pathology appeared largely normal, cerebral cortical neurons cultured from neonatal Spg20/ mice exhibited increased axon branching, a phenotype suppressed by reintroducing spartin and which required its interaction with the endosomal sorting complex required for transport (ESCRT)-III protein IST1. Analysis of the bone morphogenetic protein (BMP) signaling pathway in Spg20/ embryonic fibroblasts indicated that Smad1/5 phosphorylation is modestly elevated, possibly due to alterations in BMP receptor trafficking. Cytokinesis was impaired in embryonic fibroblasts cultured from Spg20/ mice, and binucleated chondrocytes were prominent in epiphyseal growth plates of bones in Spg20/ mice, perhaps explaining the short stature of patients. Finally, adipose tissue from Spg20/ female mice exhibited increased lipid droplet (LD) numbers and alterations in perilipin levels, supporting a role for spartin in LD maintenance. Taken together, our results support multimodal functions for spartin that provide important insights into HSP pathogenesis.
C1 [Renvoise, Benoit; Stadler, Julia; Singh, Rajat; Blackstone, Craig] NINDS, Cell Biol Sect, Neurogenet Branch, NIH, Bethesda, MD 20892 USA.
[Bakowska, Joanna C.] Loyola Univ Chicago, Stritch Sch Med, Dept Pharmacol & Expt Therapeut, Maywood, IL 60153 USA.
RP Bakowska, JC (reprint author), Loyola Univ Chicago, Stritch Sch Med, Dept Pharmacol, 2160 S 1st Ave,Bldg 102,Room 3636, Maywood, IL 60153 USA.
EM jbakowska@lumc.edu; blackstc@ninds.nih.gov
OI Singh, Rajat/0000-0002-9542-1929
FU National Institute of Neurological Disorders and Stroke; NIH R01 grant
[NS073967]
FX This research was supported by the Intramural Research Program of the
National Institute of Neurological Disorders and Stroke (B. R., J.S., R.
S. and C. B.), and NIH R01 grant NS073967 (to J.C.B.).
NR 61
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Z9 20
U1 0
U2 5
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0964-6906
J9 HUM MOL GENET
JI Hum. Mol. Genet.
PD AUG 15
PY 2012
VL 21
IS 16
BP 3604
EP 3618
DI 10.1093/hmg/dds191
PG 15
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA 981JX
UT WOS:000306964700008
PM 22619377
ER
PT J
AU Cluzeau, CVM
Watkins-Chow, DE
Fu, R
Borate, B
Yanjanin, N
Dail, MK
Davidson, CD
Walkley, SU
Ory, DS
Wassif, CA
Pavan, WJ
Porter, FD
AF Cluzeau, Celine V. M.
Watkins-Chow, Dawn E.
Fu, Rao
Borate, Bhavesh
Yanjanin, Nicole
Dail, Michelle K.
Davidson, Cristin D.
Walkley, Steven U.
Ory, Daniel S.
Wassif, Christopher A.
Pavan, William J.
Porter, Forbes D.
TI Microarray expression analysis and identification of serum biomarkers
for Niemann-Pick disease, type C1
SO HUMAN MOLECULAR GENETICS
LA English
DT Article
ID LIVER-CELL DEATH; CATHEPSIN-D; GENE-EXPRESSION; CHOLESTEROL HOMEOSTASIS;
UNESTERIFIED CHOLESTEROL; ALZHEIMERS-DISEASE; PLASMINOGEN-ACTIVATOR;
OXIDATIVE STRESS; AMYLOID-BETA; EVERY ORGAN
AB NiemannPick disease type C (NPC) is a lysosomal storage disorder characterized by liver disease and progressive neurodegeneration. Deficiency of either NPC1 or NPC2 leads to the accumulation of cholesterol and glycosphingolipids in late endosomes and early lysosomes. In order to identify pathological mechanisms underlying NPC and uncover potential biomarkers, we characterized liver gene expression changes in an Npc1 mouse model at six ages spanning the pathological progression of the disease. We identified altered gene expression at all ages, including changes in asymptomatic, 1-week-old mice. Biological pathways showing early altered gene expression included: lipid metabolism, cytochrome P450 enzymes involved in arachidonic acid and drug metabolism, inflammation and immune responses, mitogen-activated protein kinase and G-protein signaling, cell cycle regulation, cell adhesion and cytoskeleton remodeling. In contrast, apoptosis and oxidative stress appeared to be late pathological processes. To identify potential biomarkers that could facilitate monitoring of disease progression, we focused on a subset of 103 differentially expressed genes that encode secreted proteins. Further analysis identified two secreted proteins with increased serum levels in NPC1 patients: galectin-3 (LGALS3), a pro-inflammatory molecule, and cathepsin D (CTSD), a lysosomal aspartic protease. Elevated serum levels of both proteins correlated with neurological disease severity and appeared to be specific for NPC1. Expression of Lgals3 and Ctsd was normalized following treatment with 2-hydroxypropyl--cyclodextrin, a therapy that reduces pathological findings and significantly increases Npc1(/) survival. Both LGALS3 and CTSD have the potential to aid in diagnosis and serve as biomarkers to monitor efficacy in therapeutic trials.
C1 [Cluzeau, Celine V. M.; Fu, Rao; Yanjanin, Nicole; Dail, Michelle K.; Wassif, Christopher A.; Porter, Forbes D.] US Dept HHS, Program Dev Endocrinol & Genet, Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD 20892 USA.
[Watkins-Chow, Dawn E.; Pavan, William J.] US Dept HHS, Genet Dis Res Branch, NHGRI, Bethesda, MD 20892 USA.
[Borate, Bhavesh] US Dept HHS, Mol Genet Sect, Genome Technol Branch, NHGRI,NIH, Bethesda, MD 20892 USA.
[Fu, Rao] Peking Univ, Hlth Sci Ctr, Beijing 100191, Peoples R China.
[Davidson, Cristin D.; Walkley, Steven U.] Albert Einstein Coll Med, Rose F Kennedy Ctr, Dominick P Purpura Dept Neurosci, Bronx, NY 10461 USA.
[Ory, Daniel S.] Washington Univ, Sch Med, Diabet Cardiovasc Dis Ctr, St Louis, MO 63110 USA.
RP Pavan, WJ (reprint author), Bldg 49,Room 4A82,49 Convent Dr, Bethesda, MD 20892 USA.
EM bpavan@nhgri.nih.gov; fdporter@mail.nih.gov
RI Cluzeau, Celine/E-6873-2016; Davidson, Cristin/F-4889-2017;
OI Cluzeau, Celine/0000-0002-7791-6223; Davidson,
Cristin/0000-0002-5508-8113; Wassif, Christopher/0000-0002-2524-1420;
Watkins-Chow, Dawn/0000-0002-4355-0868
FU Ara Parseghian Medical Research Foundation; Dana's Angels Research
Trust; Therapeutics for Rare and Neglected Diseases program; NIH
[NS053677]; Eunice Kennedy Shriver National Institute of Child Health
and Human Development; National Human Genome Research Institute; Office
of Rare Diseases; National Institutes of Health Clinical Research Center
FX The authors received support from the Ara Parseghian Medical Research
Foundation (N.Y. and D.S.O.), Dana's Angels Research Trust (D.S.O. and
S. U. W.), the Therapeutics for Rare and Neglected Diseases program, the
NIH (grant number NS053677 to S. U. W.), the intramural research program
of the Eunice Kennedy Shriver National Institute of Child Health and
Human Development, the intramural research program of the National Human
Genome Research Institute, a Bench to Bedside award from the Office of
Rare Diseases and the National Institutes of Health Clinical Research
Center.
NR 92
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U1 0
U2 9
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0964-6906
J9 HUM MOL GENET
JI Hum. Mol. Genet.
PD AUG 15
PY 2012
VL 21
IS 16
BP 3632
EP 3646
DI 10.1093/hmg/dds193
PG 15
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA 981JX
UT WOS:000306964700010
PM 22619379
ER
PT J
AU Hutchinson, MR
Northcutt, AL
Hiranita, T
Wang, X
Lewis, SS
Thomas, J
van Steeg, K
Kopajtic, TA
Loram, LC
Sfregola, C
Galer, E
Miles, NE
Bland, ST
Amat, J
Rozeske, RR
Maslanik, T
Chapman, TR
Strand, KA
Fleshner, M
Bachtell, RK
Somogyi, AA
Yin, H
Katz, JL
Rice, KC
Maier, SF
Watkins, LR
AF Hutchinson, M. R.
Northcutt, A. L.
Hiranita, T.
Wang, X.
Lewis, S. S.
Thomas, J.
van Steeg, K.
Kopajtic, T. A.
Loram, L. C.
Sfregola, C.
Galer, E.
Miles, N. E.
Bland, S. T.
Amat, J.
Rozeske, R. R.
Maslanik, T.
Chapman, T. R.
Strand, K. A.
Fleshner, M.
Bachtell, R. K.
Somogyi, A. A.
Yin, H.
Katz, J. L.
Rice, K. C.
Maier, S. F.
Watkins, L. R.
TI Opioid Activation of Toll-Like Receptor 4 Contributes to Drug
Reinforcement
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
ID NECROSIS-FACTOR-ALPHA; MICROGLIAL ACTIVATION; AV411 IBUDILAST; MORPHINE;
EXPRESSION; ANALGESIA; REWARD; RAT; LIPOPOLYSACCHARIDE; MECHANISMS
AB Opioid action was thought to exert reinforcing effects solely via the initial agonism of opioid receptors. Here, we present evidence for an additional novel contributor to opioid reward: the innate immune pattern-recognition receptor, toll-like receptor 4 (TLR4), and its MyD88-dependent signaling. Blockade of TLR4/MD2 by administration of the nonopioid, unnatural isomer of naloxone, (+)-naloxone (rats), or two independent genetic knock-outs of MyD88-TLR4-dependent signaling (mice), suppressed opioid-induced conditioned place preference. (+)-Naloxone also reduced opioid (remifentanil) self-administration (rats), another commonly used behavioral measure of drug reward. Moreover, pharmacological blockade of morphine-TLR4/MD2 activity potently reduced morphine-induced elevations of extracellular dopamine in rat nucleus accumbens, a region critical for opioid reinforcement. Importantly, opioid-TLR4 actions are not a unidirectional influence on opioid pharmacodynamics, since TLR4(-/-) mice had reduced oxycodone-induced p38 and JNK phosphorylation, while displaying potentiated analgesia. Similar to our recent reports of morphine-TLR4/MD2 binding, here we provide a combination of in silico and biophysical data to support (+)-naloxone and remifentanil binding to TLR4/MD2. Collectively, these data indicate that the actions of opioids at classical opioid receptors, together with their newly identified TLR4/MD2 actions, affect the mesolimbic dopamine system that amplifies opioid-induced elevations in extracellular dopamine levels, therefore possibly explaining altered opioid reward behaviors. Thus, the discovery of TLR4/MD2 recognition of opioids as foreign xenobiotic substances adds to the existing hypothesized neuronal reinforcement mechanisms, identifies a new drug target in TLR4/MD2 for the treatment of addictions, and provides further evidence supporting a role for central proinflammatory immune signaling in drug reward.
C1 [Hutchinson, M. R.; Northcutt, A. L.; Wang, X.; Lewis, S. S.; Loram, L. C.; Sfregola, C.; Galer, E.; Miles, N. E.; Amat, J.; Rozeske, R. R.; Chapman, T. R.; Strand, K. A.; Bachtell, R. K.; Maier, S. F.; Watkins, L. R.] Univ Colorado Boulder, Dept Psychol & Neurosci, Ctr Neurosci, Boulder, CO 80309 USA.
[Maslanik, T.; Fleshner, M.] Univ Colorado Boulder, Dept Integrat Physiol, Ctr Neurosci, Boulder, CO 80309 USA.
[Wang, X.; Yin, H.] Univ Colorado Boulder, Dept Chem & Biochem, Ctr Neurosci, Boulder, CO 80309 USA.
[Wang, X.; Yin, H.] Univ Colorado Boulder, Biofrontiers Inst, Boulder, CO 80309 USA.
[van Steeg, K.] Univ Adelaide, Sch Med Sci, Discipline Physiol, Adelaide, SA 5005, Australia.
[Thomas, J.; Somogyi, A. A.] Univ Adelaide, Sch Med Sci, Discipline Pharmacol, Adelaide, SA 5005, Australia.
[van Steeg, K.] Univ Utrecht, Fac Sci, Div Pharmacol, NL-3805 TD Utrecht, Netherlands.
[Kopajtic, T. A.; Katz, J. L.] NIDA, Dept Hlth & Human Serv, NIH, Intramural Res Program,Biomed Res Ctr MDRB, Baltimore, MD 21224 USA.
[Bland, S. T.] Univ Colorado Denver, Dept Psychol, Denver, CO 80217 USA.
[Rice, K. C.] NIDA, Chem Biol Res Branch, NIH, Bethesda, MD 20892 USA.
[Rice, K. C.] NIAAA, NIH, Bethesda, MD 20892 USA.
RP Watkins, LR (reprint author), Univ Colorado Boulder, Dept Psychol & Neurosci, Ctr Neurosci, Campus Box 345, Boulder, CO 80309 USA.
EM linda.watkins@colorado.edu
RI Hiranita, Takato/G-6567-2011; Bachtell, Ryan/H-7436-2013; Hutchinson,
Mark/G-4147-2014; YIN, HANG/O-2097-2014; Wang, Xiaohui/B-8126-2011;
OI Bachtell, Ryan/0000-0001-5268-5927; Hutchinson,
Mark/0000-0003-2154-5950; YIN, HANG/0000-0002-9762-4818; Wang,
Xiaohui/0000-0002-3415-5612; Strand, Keith/0000-0001-8885-0162; Katz,
Jonathan/0000-0002-1068-1159
FU NIH [DA024044, DE017782, DA023132, DA025740, NS067425, DA027977,
DA026950]; NIH Intramural Research Programs of the National Institute on
Drug Abuse and the National Institute on Alcohol Abuse and Alcoholism;
International Association for the Study of Pain international
collaborative research grant; American Australian Association Merck
Company Foundation Fellowship; National Health and Medical Research
Council CJ Martin Fellowship [ID 465423]; Australian Research Council
Research Fellowship [DP110100297]; Australian Postgraduate Award; Danone
Research for Specialised Nutrition (The Netherlands) (K.vS)
FX This research was supported by NIH Grants DA024044, DE017782, DA023132,
DA025740, NS067425, DA027977, and DA026950 and by the NIH Intramural
Research Programs of the National Institute on Drug Abuse and the
National Institute on Alcohol Abuse and Alcoholism. Support was also
provided by an International Association for the Study of Pain
international collaborative research grant, an American Australian
Association Merck Company Foundation Fellowship, a National Health and
Medical Research Council CJ Martin Fellowship (ID 465423; M.R.H.
2007-2010), Australian Research Council Research Fellowship
(DP110100297; M.R.H. 2011), and Australian Postgraduate Award (J.T.) and
Danone Research for Specialised Nutrition (The Netherlands) (K.vS). We
thank Dr. David White and the NIDA Addiction Treatment Discovery Program
(NIDA ATDP) for the NovaScreen data generated through a contract with
Caliper Life Sciences as well as for the biogenic amine transporter data
generated through a contract with Research Service (R&D-22), Department
of Veterans Affairs Medical Center, Portland, OR.
NR 63
TC 76
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U1 1
U2 29
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 15
PY 2012
VL 32
IS 33
BP 11187
EP 11200
DI 10.1523/JNEUROSCI.0684-12.2012
PG 14
WC Neurosciences
SC Neurosciences & Neurology
GA 994OJ
UT WOS:000307940000004
PM 22895704
ER
PT J
AU Setiawan, VW
Pike, MC
Karageorgi, S
Deming, SL
Anderson, K
Bernstein, L
Brinton, LA
Cai, H
Cerhan, JR
Cozen, W
Chen, C
Doherty, J
Freudenheim, JL
Goodman, MT
Hankinson, SE
Lacey, JV
Liang, XL
Lissowska, J
Lu, LG
Lurie, G
Mack, T
Matsuno, RK
McCann, S
Moysich, KB
Olson, SH
Rastogi, R
Rebbeck, TR
Risch, H
Robien, K
Schairer, C
Shu, XO
Spurdle, AB
Strom, BL
Thompson, PJ
Ursin, G
Webb, PM
Weiss, NS
Wentzensen, N
Xiang, YB
Yang, HP
Yu, H
Horn-Ross, PL
De Vivo, I
AF Setiawan, Veronica Wendy
Pike, Malcolm C.
Karageorgi, Stalo
Deming, Sandra L.
Anderson, Kristin
Bernstein, Leslie
Brinton, Louise A.
Cai, Hui
Cerhan, James R.
Cozen, Wendy
Chen, Chu
Doherty, Jennifer
Freudenheim, Jo L.
Goodman, Marc T.
Hankinson, Susan E.
Lacey, James V., Jr.
Liang, Xiaolin
Lissowska, Jolanta
Lu, Lingeng
Lurie, Galina
Mack, Thomas
Matsuno, Rayna K.
McCann, Susan
Moysich, Kirsten B.
Olson, Sara H.
Rastogi, Radhai
Rebbeck, Timothy R.
Risch, Harvey
Robien, Kim
Schairer, Catherine
Shu, Xiao-Ou
Spurdle, Amanda B.
Strom, Brian L.
Thompson, Pamela J.
Ursin, Giske
Webb, Penelope M.
Weiss, Noel S.
Wentzensen, Nicolas
Xiang, Yong-Bing
Yang, Hannah P.
Yu, Herbert
Horn-Ross, Pamela L.
De Vivo, Immaculata
CA Australian Natl Endometrial Canc S
TI Age at Last Birth in Relation to Risk of Endometrial Cancer: Pooled
Analysis in the Epidemiology of Endometrial Cancer Consortium
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Review
DE endometrial neoplasms; parity; reproductive history
ID REPRODUCTIVE FACTORS; POSTMENOPAUSAL WOMEN; REPLACEMENT THERAPY;
POPULATION; COHORT; ASSOCIATION; CONSUMPTION; PROGESTIN; CARCINOMA;
PREGNANCY
AB Childbearing at an older age has been associated with a lower risk of endometrial cancer, but whether the association is independent of the number of births or other factors remains unclear. Individual-level data from 4 cohort and 13 case-control studies in the Epidemiology of Endometrial Cancer Consortium were pooled. A total of 8,671 cases of endometrial cancer and 16,562 controls were included in the analysis. After adjustment for known risk factors, endometrial cancer risk declined with increasing age at last birth (P-trend 0.0001). The pooled odds ratio per 5-year increase in age at last birth was 0.87 (95 confidence interval: 0.85, 0.90). Women who last gave birth at 40 years of age or older had a 44 decreased risk compared with women who had their last birth under the age of 25 years (95 confidence interval: 47, 66). The protective association was similar across the different age-at-diagnosis groups and for the 2 major tumor histologic subtypes (type I and type II). No effect modification was observed by body mass index, parity, or exogenous hormone use. In this large pooled analysis, late age at last birth was independently associated with a reduced risk of endometrial cancer, and the reduced risk persisted for many years.
C1 [Setiawan, Veronica Wendy; Pike, Malcolm C.; Cozen, Wendy; Mack, Thomas] Univ So Calif, Dept Prevent Med, Keck Sch Med, Los Angeles, CA 90033 USA.
[Pike, Malcolm C.; Liang, Xiaolin; Olson, Sara H.; Rastogi, Radhai] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
[Karageorgi, Stalo; De Vivo, Immaculata] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Deming, Sandra L.; Cai, Hui; Shu, Xiao-Ou] Vanderbilt Univ, Med Ctr, Nashville, TN USA.
[Anderson, Kristin; Robien, Kim] Univ Minnesota, Sch Publ Hlth, Minneapolis, MN USA.
[Bernstein, Leslie; Lacey, James V., Jr.] City Hope Natl Med Ctr, Beckman Res Inst, Duarte, CA USA.
[Brinton, Louise A.; Schairer, Catherine; Wentzensen, Nicolas; Yang, Hannah P.] NCI, Bethesda, MD 20892 USA.
[Cerhan, James R.] Mayo Clin, Rochester, MN USA.
[Chen, Chu; Doherty, Jennifer] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA.
[Freudenheim, Jo L.] SUNY Buffalo, Sch Publ Hlth & Hlth Profess, Buffalo, NY 14260 USA.
[Goodman, Marc T.; Lurie, Galina; Matsuno, Rayna K.; Thompson, Pamela J.] Univ Hawaii, Ctr Canc, Honolulu, HI 96822 USA.
[Lissowska, Jolanta] M Sklodowska Curie Mem Canc Ctr, Warsaw, Poland.
[Lissowska, Jolanta] Inst Oncol, Warsaw, Poland.
[Lu, Lingeng; Risch, Harvey; Yu, Herbert] Yale Univ, Sch Publ Hlth, New Haven, CT USA.
[Hankinson, Susan E.; De Vivo, Immaculata] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA.
[Hankinson, Susan E.; De Vivo, Immaculata] Harvard Univ, Sch Med, Boston, MA USA.
[McCann, Susan; Moysich, Kirsten B.] Roswell Pk Canc Inst, Dept Canc Prevent & Control, Buffalo, NY 14263 USA.
[Rebbeck, Timothy R.; Strom, Brian L.] Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA.
[Spurdle, Amanda B.; Webb, Penelope M.] Queensland Inst Med Res, Div Genet & Populat Hlth, Brisbane, Qld 4006, Australia.
[Ursin, Giske] Canc Registry Norway, Oslo, Norway.
[Ursin, Giske] Univ Oslo, Dept Nutr, N-0316 Oslo, Norway.
[Weiss, Noel S.] Univ Washington, Sch Publ Hlth, Seattle, WA 98195 USA.
[Xiang, Yong-Bing] Shanghai Canc Inst, Shanghai, Peoples R China.
[Horn-Ross, Pamela L.] Canc Prevent Inst Calif, Fremont, CA USA.
RP Setiawan, VW (reprint author), Univ So Calif, Dept Prevent Med, Keck Sch Med, 1450 Biggy St,Room 1517G, Los Angeles, CA 90033 USA.
EM vsetiawa@usc.edu
RI Brinton, Louise/G-7486-2015; Spurdle, Amanda/A-4978-2011;
OI Brinton, Louise/0000-0003-3853-8562; Cerhan, James/0000-0002-7482-178X;
Webb, Penelope/0000-0003-0733-5930; Spurdle, Amanda/0000-0003-1337-7897;
Lissowska, Jolanta/0000-0003-2695-5799; Robien, Kim/0000-0002-2120-2280
FU National Cancer Institute (NCI) of the National Institutes of Health
(NIH) [R03 CA135632]; National Cancer Institute [CA116543]; National
Health and Medical Research Council of Australia (NHMRC); NHMRC
[339435]; Cancer Council of Queensland; Cancer Council of Tasmania; NIH
[R01 CA58598, N01 CN67001, N01 PC35137, R01 CA39742, P01 CA87262, R01
CA082838, R01 CA092585, R01 CA48774, P30 CA14089, P01 CA77596, CA11535];
U.S. Army Medical Research Program DAMD [17-96-607]; California Breast
Cancer Research Program (CBCRP) [4JB-1106]; Department of Health and
Human Services, NCI, NIH; CBCRP fund; California Department of Public
Health [103885]; NCI; Public Health Institute, University of Southern
California; Centers for Disease Control and Prevention
FX This work was supported by a grant from the National Cancer Institute
(NCI) of the National Institutes of Health (NIH) (grant R03 CA135632 to
V. W. S.). V. W. S is supported in part by a National Cancer Institute
K07 Career Development Award (CA116543). P. M. W. and A. B. S. are
supported by fellowships from the National Health and Medical Research
Council of Australia (NHMRC). The individual studies were funded by the
following grants and agencies: Australian National Endometrial Cancer
Study: NHMRC grant 339435 and the Cancer Councils of Queensland and
Tasmania; Bay Area Women's Health Study: NIH grant R01 CA74877; controls
were collected under NIH grant R01 63446, U.S. Army Medical Research
Program DAMD grant 17-96-607, and California Breast Cancer Research
Program (CBCRP) grant 4JB-1106; Breast Cancer Detection Demonstration
Project: Intramural Research Programs of the Department of Health and
Human Services, NCI, NIH; Connecticut Endometrial Cancer Study: NIH
grant R01 CA098346; California Teachers Study: NIH grant R01CA77398 and
the CBCRP fund; the collection of cancer incidence data was supported by
the California Department of Public Health as part of the statewide
cancer reporting program mandated by California Health and Safety Code
Section 103885, the NCI's Surveillance, Epidemiology, and End Results
Program awarded to the Cancer Prevention Institute of California, the
Public Health Institute, University of Southern California, and the
Centers for Disease Control and Prevention's National Program of Cancer
Registries; Estrogen, Diet, Genetics, and Endometrial Cancer Study: NIH
grant R01 CA83918; Fred Hutchinson Cancer Research Center: NIH grants
R35 CA39779, R01 CA75977, N01 HD23166, K05 CA92002, R01 CA105212, and
R01 CA87538; Hawaii Endometrial Cancer Study: NIH grants P01 CA33619,
R01 CA58598, N01 CN67001, and N01 PC35137; Iowa Women's Health Study:
NIH grant R01 CA39742; Nurses' Health Study: NIH grants P01 CA87262 and
R01 CA082838; Polish Endometrial Cancer Study: Intramural Research Funds
of the Department of Health and Human Services, NCI, NIH; Shanghai
Endometrial Cancer Study: NIH grant R01 CA092585; US Endometrial Cancer
Study: Intramural Research Funds of the Department of Health and Human
Services, NCI, NIH; case-control study conducted by USC: NIH grants R01
CA48774 and P30 CA14089; Women's Insight and Shared Experience Study:
NIH grant P01 CA77596; and Western New York Diet Study: NIH grant
CA11535.
NR 40
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U2 6
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0002-9262
J9 AM J EPIDEMIOL
JI Am. J. Epidemiol.
PD AUG 15
PY 2012
VL 176
IS 4
BP 269
EP 278
DI 10.1093/aje/kws129
PG 10
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 988ON
UT WOS:000307500500001
PM 22831825
ER
PT J
AU Howlader, N
Noone, AM
Yu, MD
Cronin, KA
AF Howlader, Nadia
Noone, Anne-Michelle
Yu, Mandi
Cronin, Kathleen A.
TI Use of Imputed Population-based Cancer Registry Data as a Method of
Accounting for Missing Information: Application to Estrogen Receptor
Status for Breast Cancer
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Article
DE breast neoplasms; imputation; incidence; missing data; receptors;
estrogen
ID UNITED-STATES; AMERICAN SOCIETY; INCIDENCE RATES; TRENDS; WOMEN;
RECOMMENDATIONS
AB The National Cancer Institutes Surveillance, Epidemiology, and End Results (SEER) Program provides a rich source of data stratified according to tumor biomarkers that play an important role in cancer surveillance research. These data are useful for analyzing trends in cancer incidence and survival. These tumor markers, however, are often prone to missing observations. To address the problem of missing data, the authors employed sequential regression multivariate imputation for breast cancer variables, with a particular focus on estrogen receptor status, using data from 13 SEER registries covering the period 19922007. In this paper, they present an approach to accounting for missing information through the creation of imputed data sets that can be analyzed using existing software (e.g., SEERStat) developed for analyzing cancer registry data. Bias in age-adjusted trends in female breast cancer incidence is shown graphically before and after imputation of estrogen receptor status, stratified by age and race. The imputed data set will be made available in SEERStat (http://seer.cancer.gov/analysis/index.html) to facilitate accurate estimation of breast cancer incidence trends. To ensure that the imputed data set is used correctly, the authors provide detailed, step-by-step instructions for conducting analyses. This is the first time that a nationally representative, population-based cancer registry data set has been imputed and made available to researchers for conducting a variety of analyses of breast cancer incidence trends.
C1 [Howlader, Nadia; Noone, Anne-Michelle; Yu, Mandi; Cronin, Kathleen A.] NCI, Data Anal & Interpretat Branch, Surveillance Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
RP Howlader, N (reprint author), NCI, Data Anal & Interpretat Branch, Surveillance Res Program, Div Canc Control & Populat Sci, 6116 Execut Blvd,Suite 504, Bethesda, MD 20892 USA.
EM howladern@mail.nih.gov
FU Division of Cancer Control and Population Sciences, National Cancer
Institute
FX This work was supported by the Surveillance Research Program, Division
of Cancer Control and Population Sciences, National Cancer Institute.
NR 26
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U2 4
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0002-9262
J9 AM J EPIDEMIOL
JI Am. J. Epidemiol.
PD AUG 15
PY 2012
VL 176
IS 4
BP 347
EP 356
DI 10.1093/aje/kwr512
PG 10
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 988ON
UT WOS:000307500500009
PM 22842721
ER
PT J
AU Cho, Y
Kim, MS
Kim, HS
Ann, J
Lee, J
Pearce, LV
Pavlyukovets, VA
Morgan, MA
Blumberg, PM
Lee, J
AF Cho, Yongsung
Kim, Myeong Seop
Kim, Ho Shin
Ann, Jihyae
Lee, Jiyoun
Pearce, Larry V.
Pavlyukovets, Vladimir A.
Morgan, Matthew A.
Blumberg, Peter M.
Lee, Jeewoo
TI The SAR analysis of TRPV1 agonists with the alpha-methylated B-region
SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
LA English
DT Article
DE Vanilloid receptor 1; TRPV1 agonist; Capsaicin
ID VANILLOID RECEPTOR TRPV1; CAPSAICIN RECEPTOR; A-REGION; ANTAGONISTS;
PAIN; CHANNEL; ANALGESICS; MECHANISMS; ANALOGS
AB A series of TRPV1 agonists with amide, reverse amide, and thiourea groups in the B-region and their corresponding alpha-methylated analogues were investigated. Whereas the alpha-methylation of the amide B-region enhanced the binding affinities and potencies as agonists, that of the reverse amide and thiourea led to a reduction in receptor affinity. The analysis indicated that proper hydrogen bonding as well as steric effects in the B-region are critical for receptor binding. (c) 2012 Elsevier Ltd. All rights reserved.
C1 [Cho, Yongsung; Kim, Myeong Seop; Kim, Ho Shin; Ann, Jihyae; Lee, Jeewoo] Seoul Natl Univ, Coll Pharm, Pharmaceut Sci Res Inst, Seoul 151742, South Korea.
[Lee, Jiyoun] Sungshin Womens Univ, Dept Global Med Sci, Seoul 142732, South Korea.
[Pearce, Larry V.; Pavlyukovets, Vladimir A.; Morgan, Matthew A.; Blumberg, Peter M.] NCI, Lab Canc Biol & Genet, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Lee, J (reprint author), Seoul Natl Univ, Coll Pharm, Pharmaceut Sci Res Inst, Seoul 151742, South Korea.
EM jeewoo@snu.ac.kr; jeewoo@snu.ac.kr
FU NRF [R11-2007-107-02001-0]; Intramural Research Program of the National
Institutes of Health, Center for Cancer Research, National Cancer
Institute [Z1A BC 005270]
FX This research was supported by Grants R11-2007-107-02001-0 from the NRF
and was supported in part by the Intramural Research Program of the
National Institutes of Health, Center for Cancer Research, National
Cancer Institute (Project Z1A BC 005270). We thank other members of the
Blumberg group for assistance with some of the assays.
NR 22
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PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0960-894X
J9 BIOORG MED CHEM LETT
JI Bioorg. Med. Chem. Lett.
PD AUG 15
PY 2012
VL 22
IS 16
BP 5227
EP 5231
DI 10.1016/j.bmcl.2012.06.059
PG 5
WC Chemistry, Medicinal; Chemistry, Organic
SC Pharmacology & Pharmacy; Chemistry
GA 981JJ
UT WOS:000306962800014
PM 22796184
ER
PT J
AU Falade-Nwulia, O
Seaberg, EC
Rinaldo, CR
Badri, S
Witt, M
Thio, CL
AF Falade-Nwulia, Oluwaseun
Seaberg, Eric C.
Rinaldo, Charles R.
Badri, Sheila
Witt, Mallory
Thio, Chloe L.
TI Comparative Risk of Liver-Related Mortality From Chronic Hepatitis B
Versus Chronic Hepatitis C Virus Infection
SO CLINICAL INFECTIOUS DISEASES
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; OPPORTUNISTIC INFECTIONS; ANTIRETROVIRAL
THERAPY; VIRAL-HEPATITIS; NATURAL-HISTORY; HIV-INFECTION; DISEASE;
COHORT; DEATH; AIDS
AB Background. It is not known whether chronic hepatitis B (CH-B) or chronic hepatitis C (CH-C) carries a greater risk of liver-related mortality. This study compared rates of liver-related mortality between these 2 groups in the Multicenter AIDS Cohort Study (MACS).
Methods. Six hundred eighty men with CH-B (n = 337) or CH-C (n = 343) at study entry into the MACS were prospectively followed to death, last follow-up visit, or 30 March 2010, whichever came first. Four hundred seventy-two (69.4%) of these men were infected with human immunodeficiency virus type 1 (HIV-1). Causes of death were obtained from death registry matching and death certificates. Liver-related and all-cause mortality rates (MRs) were compared between groups using Poisson regression and adjusted for potential confounders and competing risks.
Results. In 6728 person-years (PYs) of follow-up, there were 293 deaths from all causes (43.5 per 1000 PYs), of which 51 were liver-related (7.6 per 1000 PYs). The all-cause MR was similar between those with CH-B and CH-C; however, the liver-related MR was significantly higher in those with CH-B (9.6 per 1000 PYs; 95% confidence interval [CI], 6.9-13.2) than those with CH-C (5.0 per 1000 PYs; 95% CI, 3.0-8.4). In the HIV-infected subgroup, which had 46 (90.2%) of the liver-related deaths, the liver-related MR remained higher from CH-B after adjusting for potential confounders (incidence rate ratio, 2.2; P = .03) and competing risks (subhazard rate ratio, 2.4; P = .02). Furthermore, among HIV-infected subjects, CD4 cell counts <200 cells/mm(3) were associated with a 16.2-fold (95% CI, 6.1-42.8) increased risk of liver-related death compared with CD4 cell counts >350 cell/mm(3).
Conclusions. Chronic hepatitis B carries a higher risk of death from liver disease than does CH-C, especially in HIV-infected men with greater immunosuppression.
C1 [Falade-Nwulia, Oluwaseun; Thio, Chloe L.] Johns Hopkins Univ, Div Infect Dis, Baltimore, MD 21287 USA.
[Falade-Nwulia, Oluwaseun] NIH, Dept Crit Care Med, Bethesda, MD 20892 USA.
[Seaberg, Eric C.] Johns Hopkins Univ, Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21287 USA.
[Rinaldo, Charles R.] Univ Pittsburgh, Dept Infect Dis & Microbiol, Pittsburgh, PA 15260 USA.
Rush Univ, Med Ctr, Div Infect Dis, John H Stroger Jr Hosp Cook Cty, Chicago, IL 60612 USA.
[Badri, Sheila; Witt, Mallory] Harbor UCLA Med Ctr, Dept Med, Torrance, CA 90509 USA.
[Badri, Sheila; Witt, Mallory] Harbor UCLA Med Ctr, Div HIV Med, Torrance, CA 90509 USA.
RP Falade-Nwulia, O (reprint author), Johns Hopkins Univ, Div Infect Dis, 1830 E Monument St,Rm 420, Baltimore, MD 21287 USA.
EM ofalade1@jhmi.edu
FU National Institute of Allergy and Infectious Diseases; National Cancer
Institute [UO1-AI-35042, UL1-RR025005, UO1-AI-35043, UO1-AI-35039,
UO1-AI-35040, UO1-AI-35041]
FX The MACS is funded by the National Institute of Allergy and Infectious
Diseases, with additional supplemental funding from the National Cancer
Institute (UO1-AI-35042, UL1-RR025005 [GCRC], UO1-AI-35043,
UO1-AI-35039, UO1-AI-35040, and UO1-AI-35041).
NR 26
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U1 0
U2 3
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1058-4838
J9 CLIN INFECT DIS
JI Clin. Infect. Dis.
PD AUG 15
PY 2012
VL 55
IS 4
BP 507
EP 513
DI 10.1093/cid/cis432
PG 7
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 977RQ
UT WOS:000306682500008
PM 22523269
ER
PT J
AU Dooley, KE
Mitnick, CD
DeGroote, MA
Obuku, E
Belitsky, V
Hamilton, CD
Makhene, M
Shah, S
Brust, JCM
Durakovic, N
Nuermberger, E
AF Dooley, Kelly E.
Mitnick, Carole D.
DeGroote, Mary Ann
Obuku, Ekwaro
Belitsky, Vera
Hamilton, Carol D.
Makhene, Mamodikoe
Shah, Sarita
Brust, James C. M.
Durakovic, Nadza
Nuermberger, Eric
CA RESIST-TB
TI Old Drugs, New Purpose: Retooling Existing Drugs for Optimized Treatment
of Resistant Tuberculosis
SO CLINICAL INFECTIOUS DISEASES
LA English
DT Article
ID EARLY BACTERICIDAL ACTIVITY; MYCOBACTERIUM-TUBERCULOSIS;
MULTIDRUG-RESISTANT; PULMONARY TUBERCULOSIS; ANTITUBERCULOSIS DRUGS;
ETHAMBUTOL RESISTANCE; THERAPY; CYCLOSERINE; AMIKACIN; CAPREOMYCIN
AB Treatment of drug-resistant tuberculosis is hindered by the high toxicity and poor efficacy of second-line drugs. New compounds must be used together with existing drugs, yet clinical trials to optimize combinations of drugs for drug-resistant tuberculosis are lacking. We conducted an extensive review of existing in vitro, animal, and clinical studies involving World Health Organization-defined group 1, 2, and 4 drugs used in drug-resistant tuberculosis regimens to inform clinical trials and identify critical research questions. Results suggest that optimizing the dosing of pyrazinamide, the injectables, and isoniazid for drug-resistant tuberculosis is a high priority. Additional pharmacokinetic, pharmacodynamic, and toxicodynamic studies are needed for pyrazinamide and ethionamide. Clinical trials of the comparative efficacy and appropriate treatment duration of injectables are recommended. For isoniazid, rapid genotypic tests for Mycobacterium tuberculosis mutations should be nested in clinical trials. Further research focusing on optimization of dose and duration of drugs with activity against drug-resistant tuberculosis is paramount.
C1 [Dooley, Kelly E.] Johns Hopkins Univ, Sch Med, Div Clin Pharmacol, Baltimore, MD 21287 USA.
[Mitnick, Carole D.] Harvard Univ, Sch Med, Boston, MA USA.
[DeGroote, Mary Ann] Colorado State Univ, Mycobacterial Res Labs, Ft Collins, CO 80523 USA.
[Obuku, Ekwaro] Univ Maryland, Sch Med, Inst Human Virol, Baltimore, MD 21201 USA.
[Obuku, Ekwaro] AIDS Relief Programme & Joint Clin Res Ctr, Kampala, Uganda.
[Belitsky, Vera; Durakovic, Nadza] Partners Hlth, Boston, MA USA.
[Hamilton, Carol D.] Family Hlth Int, Durham, NC USA.
[Makhene, Mamodikoe] NIH, Bethesda, MD 20892 USA.
[Shah, Sarita; Brust, James C. M.] Albert Einstein Coll Med, Bronx, NY 10467 USA.
RP Dooley, KE (reprint author), Johns Hopkins Univ, Sch Med, Div Clin Pharmacol, 600 N Wolfe St,Osler 527, Baltimore, MD 21287 USA.
EM kdooley1@jhmi.edu
FU National Institutes of Health [K23AI080842, K23AI083088]; Doris Duke
Charitable Foundation [2007071]
FX This work was supported by the National Institutes of Health (grant
K23AI080842 to K. E. D. and K23AI083088 to J. C. M. B.) and the Doris
Duke Charitable Foundation (Clinical Scientist Development Award 2007071
to S. S.).
NR 45
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U1 2
U2 18
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1058-4838
J9 CLIN INFECT DIS
JI Clin. Infect. Dis.
PD AUG 15
PY 2012
VL 55
IS 4
BP 572
EP 581
DI 10.1093/cid/cis487
PG 10
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 977RQ
UT WOS:000306682500018
PM 22615332
ER
PT J
AU Chi, BH
Adler, MR
Bolu, O
Mbori-Ngacha, D
Ekouevi, DK
Gieselman, A
Chipato, T
Luo, CW
Phelps, BR
McClure, C
Mofenson, LM
Stringer, JSA
AF Chi, Benjamin H.
Adler, Michelle R.
Bolu, Omotayo
Mbori-Ngacha, Dorothy
Ekouevi, Didier K.
Gieselman, Anna
Chipato, Tsungai
Luo, Chewe
Phelps, B. Ryan
McClure, Craig
Mofenson, Lynne M.
Stringer, Jeffrey S. A.
TI Progress, Challenges, and New Opportunities for the Prevention of
Mother-to-Child Transmission of HIV Under the US President's Emergency
Plan for AIDS Relief
SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
LA English
DT Article
DE prevention of mother-to-child HIV transmission; MTCT; PEPFAR; global
response; HIV
ID EARLY ANTIRETROVIRAL THERAPY; RANDOMIZED CONTROLLED-TRIAL; PROSPECTIVE
COHORT; SOUTH-AFRICA; PREGNANT-WOMEN; MALE CIRCUMCISION; INFECTED
INFANTS; INCOME COUNTRIES; DOSE NEVIRAPINE; PROGRAMS
AB In June 2011, the Joint United Nations Programme on HIV/AIDS, the US President's Emergency Plan for AIDS Relief (PEPFAR), and other collaborators outlined a transformative plan to virtually eliminate pediatric AIDS worldwide. The ambitious targets of this initiative included a 90% reduction in new pediatric HIV infections and a 50% reduction in HIV-related maternal mortality-all by 2015. PEPFAR has made an unprecedented commitment to the expansion and improvement of prevention of mother-to-child HIV transmission (PMTCT) services globally and is expected to play a critical role in reaching the virtual elimination target. To date, PEPFAR has been instrumental in the success of many national programs, including expanded coverage of PMTCT services, an enhanced continuum of care between PMTCT and HIV care and treatment, provision of more efficacious regimens for antiretroviral prophylaxis, design of innovative but simplified PMTCT approaches, and development of new strategies to evaluate program effectiveness. These accomplishments have been made through collaborative efforts with host governments, United Nations agencies, other donors (eg, the Global Fund for AIDS, Tuberculosis, and Malaria), nongovernmental organizations, and private sector partners. To successfully meet the ambitious global targets to prevent new infant HIV infections, PEPFAR must continue to leverage the existing PMTCT platform, while developing innovative approaches to rapidly expand quality HIV services. PEPFAR must also carefully integrate PMTCT into the broader combination prevention agenda for HIV, so that real progress can be made toward an "AIDS-free generation" worldwide.
C1 [Chi, Benjamin H.; Stringer, Jeffrey S. A.] Ctr Infect Dis Res Zambia, Lusaka, Zambia.
[Chi, Benjamin H.; Stringer, Jeffrey S. A.] Univ N Carolina, Chapel Hill, NC USA.
[Adler, Michelle R.; Bolu, Omotayo] Ctr Dis Control & Prevent, Global AIDS Program, Atlanta, GA USA.
[Adler, Michelle R.; Gieselman, Anna] Off Global AIDS Coordinator, Washington, DC USA.
[Mbori-Ngacha, Dorothy] UNICEF, Johannesburg, South Africa.
[Ekouevi, Didier K.] Univ Bordeaux Segalen, INSERM, U897, Bordeaux, France.
[Ekouevi, Didier K.] Programme PAC CI, Abidjan, Cote Ivoire.
[Chipato, Tsungai] Univ Zimbabwe, Harare, Zimbabwe.
[Luo, Chewe; McClure, Craig] UNICEF, New York, NY USA.
[Phelps, B. Ryan] US Agcy Int Dev, Washington, DC 20523 USA.
[Mofenson, Lynne M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Rockville, MD USA.
RP Chi, BH (reprint author), Plot 1275 Lubutu Rd,POB 34681, Lusaka, Zambia.
EM bchi@cidrz.org
RI EKOUEVI, Didier/E-7960-2014;
OI Mofenson, Lynne/0000-0002-2818-9808
NR 82
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U1 1
U2 20
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1525-4135
EI 1077-9450
J9 JAIDS-J ACQ IMM DEF
JI JAIDS
PD AUG 15
PY 2012
VL 60
SU 3
BP S78
EP S87
DI 10.1097/QAI.0b013e31825f3284
PG 10
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 981TR
UT WOS:000306994100006
PM 22797744
ER
PT J
AU El-Sadr, WM
Morrison, JS
Quinn, T
Volberding, P
AF El-Sadr, Wafaa M.
Morrison, J. Stephen
Quinn, Thomas
Volberding, Paul
TI A Chronicle of Hope and Promise: The World As It Was, As It Is, and As
It Can Be
SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
LA English
DT Article
C1 [El-Sadr, Wafaa M.] Columbia Univ, ICAP, Mailman Sch Publ Hlth, New York, NY 10032 USA.
[Morrison, J. Stephen] Ctr Strateg & Int Studies, Washington, DC 20006 USA.
[Quinn, Thomas] NIAID, Div Intramural Res, Bethesda, MD 20892 USA.
[Volberding, Paul] Univ Calif San Francisco, Dept Med, San Francisco, CA USA.
RP El-Sadr, WM (reprint author), Columbia Univ, ICAP, Mailman Sch Publ Hlth, 722 W 168th St,13th Floor, New York, NY 10032 USA.
EM wme1@columbia.edu
FU NIAID NIH HHS [P30 AI027763]
NR 0
TC 0
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U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1525-4135
J9 JAIDS-J ACQ IMM DEF
JI JAIDS
PD AUG 15
PY 2012
VL 60
SU 3
BP S49
EP S50
DI 10.1097/QAI.0b013e31825c78bb
PG 2
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 981TR
UT WOS:000306994100001
PM 22797739
ER
PT J
AU Goosby, E
Dybul, M
Fauci, AA
Fu, J
Walsh, T
Needle, R
Bouey, P
AF Goosby, Eric
Dybul, Mark
Fauci, Anthony A.
Fu, Joe
Walsh, Thomas
Needle, Richard
Bouey, Paul
TI The United States President's Emergency Plan for AIDS Relief: A Story of
Partnerships and Smart Investments to Turn the Tide of the Global AIDS
Pandemic
SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
LA English
DT Article
DE PEPFAR; HIV prevention; care; treatment
AB The United States President's Emergency Plan for AIDS Relief (PEPFAR) has played a key leadership role in the global response to the HIV/AIDS pandemic. PEPFAR was inspired by the principles of the historic Monterrey Consensus (United Nations. Monterrey Consensus on Financing for Development, Monterrey, Mexico, March 18-22, 2002. New York: United Nations; 2002. Available at: http://www.un.org/esa/ffd/monterrey/MonterreyConsensus.pdf. Accessed April 21, 2012), which changed the underlying conceptual framework for international development, and therefore global health-a shift from paternalism to partnership that begins with country ownership and requires good governance, a results-based approach, and engagement of all sectors of society. PEPFAR began with a focus on the growing emergency of the HIV/AIDS pandemic by rapidly expanding HIV services, building clinical capacity, implementing strategic information systems, and building a coalition of partners to lead the response. Within the first years of implementation, there was a shift to sustainability, including the advent of Partnership Frameworks. The PEPFAR reauthorization in 2008 codified into law, the evolution in policies and programs for the next phase of implementation. In 2011 alone, PEPFAR supported nearly 4 million people on treatment, supported programs that provided more than 1.5 million HIV-positive pregnant women with antiretroviral drugs to prevent HIV transmission to their children, and supported HIV testing for more than 40 million people. This article provides an overview of how smart investments and partnerships across sectors and US agencies have helped achieve unprecedented results in increasing HIV/AIDS services and engaging partner countries and organizations in sharing the responsibility for an AIDS-free generation.
C1 [Goosby, Eric; Fu, Joe; Walsh, Thomas; Needle, Richard; Bouey, Paul] Off US Global AIDS Coordinator, Washington, DC 20522 USA.
[Dybul, Mark] Georgetown Univ, ONeill Inst Natl & Global Hlth Law, Washington, DC USA.
[Fauci, Anthony A.] NIAID, NIH, Bethesda, MD 20892 USA.
RP Fu, J (reprint author), Off US Global AIDS Coordinator, 301 4th St SW,700, Washington, DC 20522 USA.
EM fujkh@state.gov
NR 19
TC 17
Z9 18
U1 1
U2 9
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1525-4135
J9 JAIDS-J ACQ IMM DEF
JI JAIDS
PD AUG 15
PY 2012
VL 60
SU 3
BP S51
EP S56
DI 10.1097/QAI.0b013e31825ca721
PG 6
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 981TR
UT WOS:000306994100002
PM 22797740
ER
PT J
AU Reed, JB
Njeuhmeli, E
Thomas, AG
Bacon, MC
Bailey, R
Cherutich, P
Curran, K
Dickson, K
Farley, T
Hankins, C
Hatzold, K
Justman, J
Mwandi, Z
Nkinsi, L
Ridzon, R
Ryan, C
Bock, N
AF Reed, Jason Bailey
Njeuhmeli, Emmanuel
Thomas, Anne Goldzier
Bacon, Melanie C.
Bailey, Robert
Cherutich, Peter
Curran, Kelly
Dickson, Kim
Farley, Tim
Hankins, Catherine
Hatzold, Karin
Justman, Jessica
Mwandi, Zebedee
Nkinsi, Luke
Ridzon, Renee
Ryan, Caroline
Bock, Naomi
TI Voluntary Medical Male Circumcision: An HIV Prevention Priority for
PEPFAR
SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
LA English
DT Article
DE male circumcision; HIV prevention; PEPFAR
ID RANDOMIZED CONTROLLED-TRIAL; IMMUNODEFICIENCY-VIRUS TYPE-1;
HUMAN-PAPILLOMAVIRUS; FEMALE PARTNERS; TARGET-CELLS; YOUNG MEN;
INFECTION; RISK; TRANSMISSION; KISUMU
AB As the science demonstrating strong evidence for voluntary medical male circumcision (VMMC) for HIV prevention has evolved, the President's Emergency Plan for AIDS Relief (PEPFAR) has collaborated with international agencies, donors, and partner country governments supporting VMMC programming. Mathematical models forecast that quickly reaching a large number of uncircumcised men with VMMC in strategically chosen populations may dramatically reduce community-level HIV incidence and save billions of dollars in HIV care and treatment costs. Because VMMC is a 1-time procedure that confers life-long partial protection against HIV, programs for adult men are vital short-term investments with long-term benefits. VMMC also provides a unique opportunity to reach boys and men with HIV testing and counseling services and referrals for other HIV services, including treatment. After formal recommendations by WHO in 2007, priority countries have pursued expansion of VMMC. More than 1 million males have received VMMC thus far, with the most notable successes coming from Kenya's Nyanza Province. However, a myriad of necessary cultural, political, and ethical considerations have moderated the pace of overall success. Because many millions more uncircumcised men would benefit from VMMC services now, US President Barack Obama committed PEPFAR to provide 4.7 million males with VMMC by 2014. Innovative circumcision methods-such as medical devices that remove the foreskin without injected anesthesia and/or sutures-are being rigorously evaluated. Incorporation of safe innovations into surgical VMMC programs may provide the opportunity to reach more men more quickly with services and dramatically reduce HIV incidence for all.
C1 [Reed, Jason Bailey; Bock, Naomi] US Ctr Dis Control & Prevent, Atlanta, GA USA.
[Njeuhmeli, Emmanuel] US Agcy Int Dev, Washington, DC 20523 USA.
[Thomas, Anne Goldzier] USN, Hlth Res Ctr, Dept Def HIV AIDS Program, San Diego, CA 92152 USA.
[Bacon, Melanie C.] US Natl Inst Hlth, Bethesda, MD USA.
[Bailey, Robert] Univ Illinois, Sch Publ Hlth, Chicago, IL USA.
[Curran, Kelly] Johns Hopkins Bloomberg Sch Publ Hlth, Jhpiego, Baltimore, MD USA.
[Dickson, Kim] UNICEF, Hlth Sect, New York, NY USA.
[Farley, Tim] WHO, Sigma3 Serv, Nyon, Switzerland.
[Hankins, Catherine] London Sch Hyg & Trop Med, Geneva, Switzerland.
[Hankins, Catherine] Joint United Nations Programme HIV AIDS, Geneva, Switzerland.
[Justman, Jessica] Columbia Univ, Mailman Sch Publ Hlth, Int Ctr AIDS Care & Treatment Programs, New York, NY USA.
[Mwandi, Zebedee] US Ctr Dis Control & Prevent Kenya, Nairobi, Kenya.
[Ridzon, Renee] Bill & Melinda Gates Fdn, Ahimsa Grp LLC, Seattle, WA USA.
[Ryan, Caroline] Off Global AIDS Coordinator, Washington, DC USA.
RP Reed, JB (reprint author), 1600 Clifton Rd NE,MS E-04, Atlanta, GA 30333 USA.
EM jreed1@cdc.gov
OI Hankins, Catherine/0000-0002-1642-8592
FU PEPFAR
FX Various authors receive financial support or have professional
relationships from PEPFAR (either as employees of PEPFAR-supported US
Government agencies or as grantees/contractors) as outlined in the
Copyright Transfer Agreement Forms.
NR 54
TC 15
Z9 15
U1 0
U2 9
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1525-4135
J9 JAIDS-J ACQ IMM DEF
JI JAIDS
PD AUG 15
PY 2012
VL 60
SU 3
BP S88
EP S95
DI 10.1097/QAI.0b013e31825cac4e
PG 8
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 981TR
UT WOS:000306994100007
PM 22797745
ER
PT J
AU Qian, Y
Jeong, JS
Maldonado, M
Valenzuela, JG
Gomes, R
Teixeira, C
Evangelista, F
Qaqish, B
Aoki, V
Hans, G
Rivitti, EA
Eaton, D
Diaz, LA
AF Qian, Ye
Jeong, Joseph S.
Maldonado, Mike
Valenzuela, Jesus G.
Gomes, Regis
Teixeira, Clarissa
Evangelista, Flor
Qaqish, Bahjat
Aoki, Valeria
Hans, Gunter, Jr.
Rivitti, Evandro A.
Eaton, Donald
Diaz, Luis A.
TI Cutting Edge: Brazilian Pemphigus Foliaceus Anti-Desmoglein 1
Autoantibodies Cross-React with Sand Fly Salivary LJM11 Antigen
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID FOGO SELVAGEM; LUTZOMYIA-LONGIPALPIS; IMMUNOTHERAPY; ANTIBODIES;
VULGARIS; CHAGASI; DISEASE; EPITOPE; VECTOR; VITRO
AB The environmental factors that contribute to the development of autoimmune diseases are largely unknown. Endemic pemphigus foliaceus in humans, known as Fogo Selvagem (FS) in Brazil, is mediated by pathogenic IgG4 autoantibodies against desmoglein 1 (Dsg1). Clusters of FS overlap with those of leishmaniasis, a disease transmitted by sand fly (Lutzomyia longipalpis) bites. In this study, we show that salivary Ags from the sand fly, and specifically the LJM11 salivary protein, are recognized by FS Abs. Anti-Dsg1 monoclonal autoantibodies derived from FS patients also cross-react with LJM11. Mice immunized with LJM11 generate anti-Dsg1 Abs. Thus, insect bites may deliver salivary Ags that initiate a cross-reactive IgG4 Ab response in genetically susceptible individuals and lead to subsequent FS. Our findings establish a clear relationship between an environmental, noninfectious Ag and the development of potentially pathogenic autoantibodies in an autoimmune disease. The Journal of Immunology, 2012, 189: 1535-1539.
C1 [Qian, Ye; Jeong, Joseph S.; Maldonado, Mike; Evangelista, Flor; Diaz, Luis A.] Univ N Carolina, Dept Dermatol, Chapel Hill, NC 27599 USA.
[Valenzuela, Jesus G.; Gomes, Regis; Teixeira, Clarissa] NIAID, Vector Mol Biol Sect, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA.
[Qaqish, Bahjat] Univ N Carolina, Dept Biostat, Chapel Hill, NC 27599 USA.
[Aoki, Valeria; Rivitti, Evandro A.] Univ Sao Paulo, Dept Dermatol, BR-05508 Sao Paulo, Brazil.
[Hans, Gunter, Jr.; Eaton, Donald] Univ Fed Mato Grosso do Sul, Dept Dermatol, BR-79070900 Mato Grosso, Brazil.
RP Diaz, LA (reprint author), Univ N Carolina, Dept Dermatol, CB 7287, Chapel Hill, NC 27599 USA.
EM luis_diaz@med.unc.edu
RI Aoki, Valeria/H-1415-2012
FU National Institutes of Health [R01 AR30281, R01 AR32599, K01 AR056378];
Dermatology Foundation research award; American Skin Association Alice
P. Melly research grant
FX This work was supported in part by National Institutes of Health Grants
R01 AR30281, R01 AR32599 (to L.A.D.), and K01 AR056378 (to Y.Q.). Y.Q.
was also supported by a Dermatology Foundation research award and an
American Skin Association Alice P. Melly research grant.
NR 23
TC 18
Z9 18
U1 1
U2 5
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD AUG 15
PY 2012
VL 189
IS 4
BP 1535
EP 1539
DI 10.4049/jimmunol.1200842
PG 5
WC Immunology
SC Immunology
GA 984TW
UT WOS:000307216000002
PM 22798673
ER
PT J
AU Vargas-Inchaustegui, DA
Xiao, P
Tuero, I
Patterson, LJ
Robert-Guroff, M
AF Vargas-Inchaustegui, Diego A.
Xiao, Peng
Tuero, Iskra
Patterson, L. Jean
Robert-Guroff, Marjorie
TI NK and CD4(+) T Cell Cooperative Immune Responses Correlate with Control
of Disease in a Macaque Simian Immunodeficiency Virus Infection Model
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID NATURAL-KILLER-CELLS; ACUTE HIV-1 INFECTION; INNATE IMMUNITY; RHESUS
MACAQUES; SIV INFECTION; ELITE CONTROLLERS; DENDRITIC CELLS; IFN-GAMMA;
MUCOSAL; REPLICATION
AB Control of infectious disease may be accomplished by successful vaccination or by complex immunologic and genetic factors favoring Ag-specific multicellular immune responses. Using a rhesus macaque model, we evaluated Ag-specific T cell-dependent NK cell immune responses in SIV-infected macaques, designated "controlling" or "noncontrolling" based on long-term chronic viremia levels, to determine whether NK cell effector functions contribute to control of SIV infection. We observed that Gag stimulation of macaque PBMCs induced subset-specific NK cell responses in SIV-controlling but not SIV-noncontrolling animals, as well as that circulatory NK cell responses were dependent on Ag-specific IL-2 production by CD4(+) central memory T cells. NK cell activation was blocked by anti-IL-2-neutralizing Ab and by CD4(+) T cell depletion, which abrogated the Gag-specific responses. Among tissue-resident cells, splenic and circulatory NK cells displayed similar activation profiles, whereas liver and mucosal NK cells displayed a decreased activation profile, similar in SIV-controlling and -noncontrolling macaques. Lack of T cell-dependent NK cell function was rescued in SIV-noncontrolling macaques through drug-mediated control of viremia. Our results indicate that control of disease progression in SIV-controlling macaques is associated with cooperation between Ag-specific CD4(+) T cells and NK cell effector function, which highlight the importance of such cell-to-cell cooperativity in adaptive immunity and suggest that this interaction should be further investigated in HIV vaccine development and other prophylactic vaccine approaches. The Journal of Immunology, 2012, 189: 1878-1885.
C1 [Vargas-Inchaustegui, Diego A.; Xiao, Peng; Tuero, Iskra; Patterson, L. Jean; Robert-Guroff, Marjorie] NCI, Vaccine Branch, NIH, Bethesda, MD 20892 USA.
RP Robert-Guroff, M (reprint author), NCI, Vaccine Branch, NIH, 41 Medlars Dr,Bldg 41,Room D804, Bethesda, MD 20892 USA.
EM guroffm@mail.nih.gov
FU Intramural Research Program of the National Institutes of Health,
National Cancer Institute
FX This work was supported by the Intramural Research Program of the
National Institutes of Health, National Cancer Institute.
NR 47
TC 16
Z9 16
U1 0
U2 3
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD AUG 15
PY 2012
VL 189
IS 4
BP 1878
EP 1885
DI 10.4049/jimmunol.1201026
PG 8
WC Immunology
SC Immunology
GA 984TW
UT WOS:000307216000040
PM 22798665
ER
PT J
AU Sarkar, T
Nguyen, TL
Su, ZW
Hao, J
Bai, RL
Gussio, R
Qiu, SX
Hamel, E
AF Sarkar, Taradas
Tam Luong Nguyen
Su, Zhi-Wei
Hao, Jun
Bai, Ruoli
Gussio, Rick
Qiu, Samuel X.
Hamel, Ernest
TI Interaction of pseudolaric acid B with the colchicine site of tubulin
SO BIOCHEMICAL PHARMACOLOGY
LA English
DT Article
ID BETA-TUBULIN; ANTIMITOTIC AGENTS; BINDING; THIOCOLCHICINE;
POLYMERIZATION; FLUORESCENCE; INHIBITORS; MECHANISM; KINETICS; ISOTYPES
AB We purified pseudolaric acid B (PAB) from the root and stem bark of Pseudolarix kaempferi (Lindl.) Gorden. Confirming previous findings, we found that the compound had high nanomolar IC50 antiproliferative effects in several cultured cell lines, causing mitotic arrest and the disappearance of intracellular microtubules. PAB strongly inhibited tubulin assembly (IC50, 1.1 mu M) but weakly inhibited the binding of colchicine to tubulin, as demonstrated by fluorescence and with [H-3]-colchicine. Kinetic analysis demonstrated that the mechanism of inhibition was competitive, with an apparent K-i of 12-15 mu M. Indirect studies demonstrated that PAB bound rapidly to tubulin and dissociated more rapidly from tubulin than the colchicine analog 2-methoxy-5-(2',3',4'-trimethoxyphenyl)tropone, whose complex with tubulin is known to have a half-life of 17 s at 37 degrees C. We modeled PAB into the colchicine site of tubulin, using the crystal structure 1SA0 that contains two alpha beta-tubulin heterodimers, both bound to a colchicinoid and to a stathmin fragment. The binding model of PAB revealed common pharmacophoric features between PAB and colchicinoids, not readily apparent from their chemical structures. Published by Elsevier Inc.
C1 [Su, Zhi-Wei; Hao, Jun; Qiu, Samuel X.] Chinese Acad Sci, S China Bot Garden, Key Lab Plant Resources Conservat & Sustainable U, Program Nat Prod Med Chem & Drug Discovery, Guangzhou 510650, Peoples R China.
[Sarkar, Taradas; Bai, Ruoli; Hamel, Ernest] NCI, Screening Technol Branch, Dev Therapeut Program, Div Canc Treatment & Diag,NIH, Frederick, MD 21702 USA.
[Su, Zhi-Wei; Hao, Jun; Qiu, Samuel X.] NCI, Informat Technol Branch, Dev Therapeut Program, Div Canc Treatment & Diag,NIH, Frederick, MD 21702 USA.
[Tam Luong Nguyen] NCI, Target Struct Based Drug Discovery Grp, SAIC Frederick Inc, Frederick, MD 21702 USA.
RP Qiu, SX (reprint author), Chinese Acad Sci, S China Bot Garden, Key Lab Plant Resources Conservat & Sustainable U, Program Nat Prod Med Chem & Drug Discovery, 723 Xingke Ave, Guangzhou 510650, Peoples R China.
EM sxqiu@scbg.ac.cn; hamele@mail.nih.gov
FU Chinese National Science and Technology Major Project [2009ZX09103-436];
Guangzhou Municipal Science and Technology Major Project [2009A1-E011];
National Cancer Institute, National Institutes of Health
[HHSN261200800001E]; Division of Cancer Treatment and Diagnosis of the
National Cancer Institute
FX This work was partially supported by the following awards to SXQ:
Chinese National Science and Technology Major Project (No.
2009ZX09103-436) and Guangzhou Municipal Science and Technology Major
Project (No. 2009A1-E011). This work has been funded in part with
federal funds from the National Cancer Institute, National Institutes of
Health, under contract HHSN261200800001E. The content of this
publication does not necessarily reflect the views or policies of the
Department of Health and Human Services, nor does mention of trade
names, commercial products, or organizations imply endorsement by the US
Government. This research was supported in part by the Developmental
Therapeutics Program in the Division of Cancer Treatment and Diagnosis
of the National Cancer Institute. We also thank Drs. John J. Correia
(University of Mississippi Medical Center) and Richard F. Luduena
(University of Texas Health Science Center) for their assistance and
advice on beta-tubulin isotypes.
NR 27
TC 11
Z9 11
U1 1
U2 4
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0006-2952
J9 BIOCHEM PHARMACOL
JI Biochem. Pharmacol.
PD AUG 15
PY 2012
VL 84
IS 4
BP 444
EP 450
DI 10.1016/j.bcp.2012.05.014
PG 7
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 983RE
UT WOS:000307135600005
PM 22634405
ER
PT J
AU Fogel, JM
Taha, TE
Sun, J
Hoover, DR
Parsons, TL
Kumwenda, JJ
Mofenson, LM
Fowler, MG
Hendrix, CW
Kumwenda, NI
Eshleman, SH
Mirochnick, M
AF Fogel, Jessica M.
Taha, Taha E.
Sun, Jin
Hoover, Donald R.
Parsons, Teresa L.
Kumwenda, Johnstone J.
Mofenson, Lynne M.
Fowler, Mary Glenn
Hendrix, Craig W.
Kumwenda, Newton I.
Eshleman, Susan H.
Mirochnick, Mark
TI Stavudine Concentrations in Women Receiving Postpartum Antiretroviral
Treatment and Their Breastfeeding Infants
SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
LA English
DT Article
DE stavudine concentrations; breast milk; mother-to-child transmission; HIV
ID MILK; 2',3'-DIDEHYDRO-3'-DEOXYTHYMIDINE; MOTHERS
AB First-line antiretroviral treatment regimens in resource-limited settings used in breastfeeding mothers often include stavudine (d4T). Limited data describing d4T concentrations in breast milk are available. We analyzed d4T concentrations in 52 mother-infant pairs using ultra-performance liquid chromatography-tandem mass spectrometry (lower limit of quantification: 5 ng/mL in plasma, 20 ng/mL in breast milk). Median (interquartile range) d4T concentrations were 86 (36-191) ng/mL in maternal plasma, 151 (48-259) ng/mL in whole milk, 190 (58-296) ng/mL in skim milk, and <5 (<5 to <5) ng/mL in infant plasma. Although d4T is concentrated in breast milk relative to maternal plasma, the infant d4T dose received from breast milk is very small and not clinically significant.
C1 [Fogel, Jessica M.] Johns Hopkins Univ, Sch Med, Johns Hopkins Med Inst, Dept Pathol, Baltimore, MD 21205 USA.
[Taha, Taha E.; Sun, Jin; Kumwenda, Newton I.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA.
[Hoover, Donald R.] Rutgers State Univ, Dept Stat & Biostat, Piscataway, NJ USA.
[Hoover, Donald R.] Rutgers State Univ, Inst Hlth Hlth Care Policy & Aging Res, Piscataway, NJ USA.
[Parsons, Teresa L.; Hendrix, Craig W.] Johns Hopkins Univ, Sch Med, Dept Med Clin Pharmacol, Baltimore, MD 21205 USA.
[Kumwenda, Johnstone J.] Univ Malawi, Coll Med, Dept Med, Blantyre, Malawi.
[Mofenson, Lynne M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pediat Adolescent & Maternal AIDS Branch, NIH, Rockville, MD USA.
[Mirochnick, Mark] Boston Univ, Sch Med, Dept Pediat, Boston, MA 02118 USA.
RP Fogel, JM (reprint author), Johns Hopkins Univ, Sch Med, Johns Hopkins Med Inst, Dept Pathol, Ross Bldg,Room 646,720 Rutland Ave, Baltimore, MD 21205 USA.
EM jfogel@jhmi.edu
RI Hendrix, Craig/G-4182-2014;
OI Hendrix, Craig/0000-0002-5696-8665; Mofenson, Lynne/0000-0002-2818-9808
FU National Institute of Allergy and Infectious Diseases (NIAID/NIH)
[R01-AI087139]; International Maternal Pediatric and Adolescent AIDS
Clinical Trials (IMPAACT) Network [UM1-AI068632]; HIV Prevention Trials
Network (HPTN); NIAID; National Institute on Drug Abuse; National
Institute of Mental Health; Office of AIDS Research, of the NIH,
Department of Health and Human Services [UM1-AI068613]
FX Supported by (1) the National Institute of Allergy and Infectious
Diseases (NIAID/NIH) R01-AI087139 (to S.H.E); (2) the International
Maternal Pediatric and Adolescent AIDS Clinical Trials (IMPAACT) Network
(UM1-AI068632); and (3) the HIV Prevention Trials Network (HPTN)
sponsored by NIAID, the National Institute on Drug Abuse, the National
Institute of Mental Health, and the Office of AIDS Research, of the NIH,
Department of Health and Human Services (UM1-AI068613).
NR 17
TC 2
Z9 2
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1525-4135
J9 JAIDS-J ACQ IMM DEF
JI JAIDS
PD AUG 15
PY 2012
VL 60
IS 5
BP 462
EP 465
DI 10.1097/QAI.0b013e31825ddcfa
PG 4
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 981TV
UT WOS:000306994500005
PM 22614899
ER
PT J
AU Wilkin, TJ
Lalama, CM
McKinnon, J
Gandhi, RT
Lin, NN
Landay, A
Ribaudo, H
Fox, L
Currier, JS
Mellors, JW
Gulick, R
Tenorio, AR
AF Wilkin, Timothy J.
Lalama, Christina M.
McKinnon, John
Gandhi, Rajesh T.
Lin, Nina
Landay, Alan
Ribaudo, Heather
Fox, Lawrence
Currier, Judith S.
Mellors, John W.
Gulick, Roy
Tenorio, Allan R.
TI A Pilot Trial of Adding Maraviroc to Suppressive Antiretroviral Therapy
for Suboptimal CD4(+) T-Cell Recovery Despite Sustained Virologic
Suppression: ACTG A5256
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; HIV-INFECTED PATIENTS; LYMPHOCYTE
ACTIVATION; CORECEPTOR USAGE; HAART ERA; COUNT; COMBINATION; CCR5;
DEATH; AIDS
AB Background. Despite viral suppression, antiretroviral therapy (ART) does not restore CD4(+) T-cell counts in many patients infected with human immunodeficiency virus type 1 (HIV-1).
Methods. In a single-arm pilot trial involving ART recipients with suppressed plasma levels of HIV-1 RNA for at least 48 weeks and stable suboptimal CD4(+) T-cell recovery, subjects added maraviroc, a CCR5 antagonist, to their existing ART for 24 weeks. After stopping maraviroc, they were followed for an additional 24 weeks. A Wilcoxon signed-rank test was used to evaluate whether maraviroc was associated with an increase of at least 20 cells/mu L in the CD4(+) T-cell count.
Results. A total of 34 subjects were enrolled. The median age was 50 years, and the median baseline CD4(+) T-cell count was 153 cells/mu L. The median increase in CD4(+) T-cell count from baseline to week 22/24 was 12 cells/mu L (90% confidence interval, 1-22). A CD4(+) T-cell count increase of at least 20 cells/mu L was not detected (P = .97). Markers of immune activation and apoptosis decreased during maraviroc intensification; this decline partially reversed after discontinuing maraviroc.
Conclusions. Adding maraviroc to suppressive ART for 24 weeks was not associated with an increase in CD4(+) T-cell counts of at least 20 cells/mu L. Further studies of CCR5 antagonists in the dampening of immune activation associated with HIV infection are warranted.
C1 [Wilkin, Timothy J.; Gulick, Roy] Weill Cornell Med Coll, Div Infect Dis, New York, NY 10011 USA.
[Lalama, Christina M.; Ribaudo, Heather] Harvard Univ, Sch Publ Hlth, Ctr Biostat AIDS Res, Boston, MA 02115 USA.
[McKinnon, John; Mellors, John W.] Univ Pittsburgh, Dept Med, Div Infect Dis, Pittsburgh, PA 15260 USA.
[Gandhi, Rajesh T.; Lin, Nina] Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA.
[Gandhi, Rajesh T.] Ragon Inst, Boston, MA USA.
[Lin, Nina] Harvard Univ, Sch Med, Boston, MA USA.
[Landay, Alan] Rush Univ, Med Ctr, Dept Immunol Microbiol, Chicago, IL 60612 USA.
[Fox, Lawrence] NIAID, Div AIDS, NIH, Bethesda, MD 20892 USA.
[Currier, Judith S.] Univ Calif Los Angeles, Div Infect Dis, Los Angeles, CA USA.
[Tenorio, Allan R.] Rush Univ, Med Ctr, Infect Dis Sect, Chicago, IL 60612 USA.
[Tenorio, Allan R.] Univ Philippines, Coll Med, Manila, Philippines.
RP Wilkin, TJ (reprint author), Weill Cornell Med Coll, Div Infect Dis, 119 W 24th St, New York, NY 10011 USA.
EM tiw2001@med.cornell.edu
FU National Institute of Allergy and Infectious Diseases [U01 AI68636,
AI068634, AI045008, AI050409, AI050410, AI060354, AI082151, K24 AI51966,
R01 AI066992-04A1]; National Institute of Allergy and Infectious
Diseases (Virology Support Laboratory) [204VC009]; National Institute of
Allergy and Infectious Diseases (Statistical and Data Analysis Center)
[AI069418, AI069419, AI069423, AI069424, AI069432, AI069439, AI069447,
AI069452, AI069465, AI069471, AI069472, AI069474, AI069477, AI069484,
AI069494, AI069495, AI69501, AI069502, AI069503, AI069511, AI069532,
AI069556]; National Center for Research Resources [RR023561, RR024160,
RR 025747, RR024975, RR024996]; National Library of Medicine
[G08LM008830-01]; Pfizer; Tibotec; Gilead Sciences; Merck; ViiV
FX National Institute of Allergy and Infectious Diseases (grant U01 AI68636
to the AIDS Clinical Trials Group; Virology Support Laboratory
subcontract 204VC009 to the University of Pittsburgh; grant AI068634 to
the Statistical and Data Analysis Center; grants AI069418, AI069419,
AI069423, AI069424, AI069432, AI069439, AI069447, AI069452, AI069465,
AI069471, AI069472, AI069474, AI069477, AI069484, AI069494, AI069495,
AI69501, AI069502, AI069503, AI069511, AI069532, and AI069556 to
participating clinical trial units; grants AI045008, AI050409, AI050410,
AI060354, and AI082151 to the Centers for AIDS Research; grant K24
AI51966 to R. M. G.; and grant R01 AI066992-04A1 to R. T. G.); National
Center for Research Resources (grants RR023561, RR024160, RR 025747,
RR024975, and RR024996 to the Clinical and Translational Science
Centers); National Library of Medicine (grant G08LM008830-01 to R. T.
G.); and Pfizer Investigator-Initiated Research Grant (funds for assays
and supply of maraviroc).; T. J. W. has served as an ad hoc consultant
to Pfizer and Quest Diagnostics and as site principal investigator for
research grants (to Weill Cornell Medical College) for Tibotec and
GlaxoSmithKline. R. T. G. has received grant support from Tibotec and
Gilead Sciences. A. L. receives research grants from Merck and Tobira
and has served as a consultant to Merck. J. S. C. has served as the
principal investigator for research grants (to UCLA) for Merck and
Tibotec. J. W. M. is a consultant for Gilead Sciences, Merck, and RFS
Pharma and owns share options in RFS Pharma. R. M. G. served as an ad
hoc consultant for Bristol-Myers, Gilead Sciences, GlaxoSmithKline,
Janssen, Merck, ViiV, and Virostatics and as site principal investigator
for research grants (to Weill Cornell Medical College) for Merck,
Pfizer, and ViiV. A. R. T. has served as an ad hoc consultant to Johnson
& Johnson and as principal investigator for research grants from Abbott
and Gilead Sciences. All other authors report no potential conflicts.
NR 35
TC 45
Z9 45
U1 0
U2 5
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0022-1899
J9 J INFECT DIS
JI J. Infect. Dis.
PD AUG 15
PY 2012
VL 206
IS 4
BP 534
EP 542
DI 10.1093/infdis/jis376
PG 9
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 977MQ
UT WOS:000306667000011
PM 22740718
ER
PT J
AU Corton, JC
Bushel, PR
Fostel, J
O'Lone, RB
AF Corton, J. Christopher
Bushel, Pierre R.
Fostel, Jennifer
O'Lone, Raegan B.
TI Sources of variance in baseline gene expression in the rodent liver
SO MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS
LA English
DT Review
DE Toxicogenomics; Baseline expression; Microarray; Fasting; Sex; Circadian
rhythm; Microbiota; Life stage; Diet
ID MOUSE-LIVER; RAT-LIVER; MICROARRAY ANALYSIS; DRUG-METABOLISM;
SUPRACHIASMATIC NUCLEUS; COPPER DISTRIBUTION; NEWBORN LIVER; SEX;
ENZYMES; FEMALE
AB The use of gene expression profiling in both clinical and laboratory settings would be enhanced by better characterization of variation due to individual, environmental, and technical factors. Analysis of microarray data from untreated or vehicle-treated animals within the control arm of toxicogenomics studies has yielded useful information on baseline fluctuations in liver gene expression in the rodent. Here, studies which highlight contributions of different factors to gene expression variability in the rodent liver are discussed including a large meta-analysis of rat liver, which identified genes that vary in control animals in the absence of chemical treatment. Genes and their pathways that are the most and least variable were identified in a number of these studies. Life stage, fasting, sex, diet, circadian rhythm and liver lobe source can profoundly influence gene expression in the liver. Recognition of biological and technical factors that contribute to variability of background gene expression can help the investigator in the design of an experiment that maximizes sensitivity and reduces the influence of confounders that may lead to misinterpretation of genomic changes. The factors that contribute to variability in liver gene expression in rodents are likely analogous to those contributing to human interindividual variability in drug response and chemical toxicity. Identification of batteries of genes that are altered in a variety of background conditions could be used to predict responses to drugs and chemicals in appropriate models of the human liver. Published by Elsevier B.V.
C1 [Corton, J. Christopher] US EPA, Integrated Syst Toxicol Div, Natl Hlth & Environm Effects Res Lab, Res Triangle Pk, NC 27711 USA.
[Bushel, Pierre R.] Natl Inst Environm Hlth Sci, Biostat Branch, Res Triangle Pk, NC USA.
[Fostel, Jennifer] Natl Inst Environm Hlth Sci, Natl Toxicol Program, Res Triangle Pk, NC USA.
[O'Lone, Raegan B.] ILSI Hlth & Environm Sci Inst, Washington, DC USA.
RP Corton, JC (reprint author), US EPA, Integrated Syst Toxicol Div, Natl Hlth & Environm Effects Res Lab, 109 TW Alexander Dr,MD-B143-06, Res Triangle Pk, NC 27711 USA.
EM corton.chris@epa.gov
FU HESI Genomics Technical Committee; ILSI HESI; Division of the National
Toxicology Program; Intramural Research Program of the National
Institutes of Health (NIH); National Institute of Environmental Health
Sciences (NIEHS) [Z01 ES102345-04]; U.S. Environmental Protection Agency
FX We would like to thank Drs. Brian Chorley and Mitch Rosen for their
critical review, the HESI Genomics Technical Committee for supporting
the work, and to members of the committee who contributed microarray
data for this and on-going analyses. Some of the work described was
carried out by a subgroup of the HESI Application of Genomics to
Mechanism-Based Risk Assessment Technical Committee, funded through ILSI
HESI. This research was supported by the Division of the National
Toxicology Program, the Intramural Research Program of the National
Institutes of Health (NIH) and National Institute of Environmental
Health Sciences (NIEHS) [Z01 ES102345-04]. The information in this
document has been supported by the U.S. Environmental Protection Agency.
It has been subjected to review by the National Health and Environmental
Effects Research Laboratory and approved for publication. Approval does
not signify that the contents reflect the views of the Agency, nor does
mention of trade names or commercial products constitute endorsement or
recommendation for use.
NR 79
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PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1383-5718
EI 1879-3592
J9 MUTAT RES-GEN TOX EN
JI Mutat. Res. Genet. Toxicol. Environ. Mutagen.
PD AUG 15
PY 2012
VL 746
IS 2
SI SI
BP 104
EP 112
DI 10.1016/j.mrgentox.2011.12.017
PG 9
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology
GA 972TW
UT WOS:000306304400003
PM 22230429
ER
PT J
AU Bandettini, PA
AF Bandettini, Peter A.
TI Twenty years of functional MRI: The science and the stories
SO NEUROIMAGE
LA English
DT Review
DE fMRI; Functional MRI; Brain imaging; Brain; MRI; Blood; High field;
Cognitive neuroscience; Neuroscience; Hemoglobin; Neurovascular
coupling; Brain function
ID CEREBRAL-BLOOD-FLOW; HUMAN VISUAL-CORTEX; EVENT-RELATED FMRI; BOLD
POSTSTIMULUS UNDERSHOOT; TRANSVERSE RELAXATION-TIME; NUCLEAR
MAGNETIC-RESONANCE; HIGH-RESOLUTION FMRI; HUMAN BRAIN ACTIVITY; 1ST
ADVANCING FMRI; ULTRA-HIGH FIELD
AB Since its inception over twenty years ago, the field of functional magnetic resonance imaging (fMRI) has grown in usage, sophistication, range of applications, and impact. After twenty years, it's useful to briefly look back as well as forward to size up just how far we have come and speculate just how far we may go. This is an introduction to the special issue of "Twenty years of fMRI: the science and the stories." The one-hundred and three papers in this special issue highlight the major methodological developments and controversies of fMRI from a first person perspective over the past twenty years. The growth of this field is not just fascinating from a science and technology perspective, but also from a human perspective. Most who were fortunate enough to be part of this effort at the beginning, as well as those who jumped in along the way have their fair share of interesting stories consisting of top rate science as well as intense thought and effort, good or bad fortune, and some claim to a contribution. These stories are in the following papers, written by the current leaders in the field and the innovators throughout the twenty year history. The categories, designed to cover every aspect of the emergence and development of fMRI, include: pre-fMRI: the first BOLD brain activation results; developments in pulse sequences, imaging methods, and hardware for fMRI; methodological developments, issues, and mechanisms; new paradigm designs; education; and the future. Within this issue, we have a collage of overlapping, complementary, yet sometimes contradictory accounts of what happened during the breathtakingly diverse and intense development of this still growing field over the past twenty years. (C) 2012 Published by Elsevier Inc.
C1 NIMH, Sect Funct Imaging Methods & Funct MRI Facil, Bethesda, MD 20892 USA.
RP Bandettini, PA (reprint author), NIMH, Sect Funct Imaging Methods & Funct MRI Facil, Bldg 10,Room 1D80,10 Ctr Dr MSC 1148, Bethesda, MD 20892 USA.
EM bandettini@nih.gov
FU Intramural NIH HHS
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PI SAN DIEGO
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SN 1053-8119
J9 NEUROIMAGE
JI Neuroimage
PD AUG 15
PY 2012
VL 62
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SI SI
BP 575
EP 588
DI 10.1016/j.neuroimage.2012.04.026
PG 14
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 973WK
UT WOS:000306390600001
PM 22542637
ER
PT J
AU Koretsky, AP
AF Koretsky, Alan P.
TI Early development of arterial spin labeling to measure regional brain
blood flow by MRI
SO NEUROIMAGE
LA English
DT Review
DE Perfusion MRI; Magnetization transfer; Functional MRI; Blood flow
tracers
ID NUCLEAR-MAGNETIC-RESONANCE; FREE-INDUCTION DECAYS; RAT-BRAIN; CONTRAST
AGENTS; AMPHETAMINE STIMULATION; SENSORY STIMULATION;
EXCHANGE-REACTIONS; NMR-SPECTROSCOPY; RADIO-FREQUENCY; PERFUSION MRI
AB Two major avenues of work converged in the late 1980's and early 1990's to give rise to brain perfusion MRI. The development of anatomical brain MRI quickly had as a major goal the generation of angiograms using tricks to label flowing blood in macroscopic vessels. These ideas were aimed at getting information about microcirculatory flow as well. Over the same time course the development of in vivo magnetic resonance spectroscopy had as its primary goal the assessment of tissue function and in particular, tissue energetics. For this the measurement of the delivery of water to tissue was critical for assessing tissue oxygenation and viability. The measurement of the washin/washout of "freely" diffusible tracers by spectroscopic based techniques pointed the way for quantitative approaches to measure regional blood flow by MRI. These two avenues came together in the development of arterial spin labeling (ASL) MRI techniques to measure regional cerebral blood flow. The early use of ASL to measure brain activation to help verify BOLD fMRI led to a rapid development of ASL based perfusion MRI. Today development and applications of regional brain blood flow measurements with ASL continues to be a major area of activity. (C) 2012 Published by Elsevier Inc.
C1 NINDS, LFMI, NIH, Bethesda, MD 20892 USA.
RP Koretsky, AP (reprint author), NINDS, LFMI, NIH, Bldg 10,Rm B1D728,10 Ctr Dr, Bethesda, MD 20892 USA.
EM koretskya@ninds.nih.gov
RI Koretsky, Alan/C-7940-2015
OI Koretsky, Alan/0000-0002-8085-4756
FU NINDS, NIH
FX I would like to acknowledge Don Williams, John Detre, Afonso Silva,
Lalith Talagala, and Jeff Duyn for their careful reading of the
manuscript. Lalith Talagala supplied the images in Fig. 1. I would also
like to acknowledge Peter Bandettini for the kind invitation to describe
the early history of ASL from my own perspective. A nice opportunity to
be self-indulgent, I ask the readers for their forgiveness. Dr. Koretsky
is supported by the intramural research program of NINDS, NIH.
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SN 1053-8119
J9 NEUROIMAGE
JI Neuroimage
PD AUG 15
PY 2012
VL 62
IS 2
SI SI
BP 602
EP 607
DI 10.1016/j.neuroimage.2012.01.005
PG 6
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 973WK
UT WOS:000306390600004
PM 22245338
ER
PT J
AU Bandettini, PA
AF Bandettini, Peter A.
TI Sewer pipe, wire, epoxy, and finger tapping: The start of fMRI at the
Medical College of Wisconsin
SO NEUROIMAGE
LA English
DT Review
ID HUMAN VISUAL-CORTEX; NUCLEAR MAGNETIC-RESONANCE; HUMAN BRAIN ACTIVATION;
FUNCTIONAL MRI; SENSORY STIMULATION; HIGH-RESOLUTION; SPIN-ECHO; 1.5 T;
BLOOD; TIME
AB In 1991, the Biophysics Research Institute at the Medical College of Wisconsin was among the first groups to develop functional Magnetic Resonance Imaging (fMRI). Our story is unique on a few levels: We didn't have knowledge of the ability to image human brain activation with MRI using blood oxygenation dependent (BOLD) contrast until early August of 1991 when we attended the Society for Magnetic Resonance in Medicine (SMRM) meeting in San Francisco, yet we produced our first BOLD-based maps of motor cortex activation about a month later. The effort started with two graduate students, Eric Wong and myself. Only a few days prior to that extremely important SMRM meeting, we had developed human echo planar imaging (EPI) capability in-house. Wong designed, built, and interfaced a head gradient coil made out of sewer pipe, wire, and epoxy to a standard GE 1.5 T MRI scanner. Also, a few months prior to building this human head gradient coil he developed the EPI pulse sequences and image reconstruction. All of these efforts were towards a different goal for demonstration of Wong's novel approach to perfusion imaging in the human brain. Following SMRM, where a plenary lecture by Tom Brady from MGH opened our eyes to human brain activation imaging using BOLD contrast, and where we learned that EPI was extremely helpful if not critical to its success, we worked quickly to achieve our first results on September 14, 1991. The story is also unique in that Jim Hyde had set up the Biophysics Research Institute to be optimal for just this type of rapidly advancing basic technology research. It was well equipped for hardware development, had open and dynamic collaborative relationships with other departments, hospitals on campus, and GE, and had a relatively flat hierarchy and relaxed, flexible, collegial atmosphere internally. Since these first brain activation results, MCW Biophysics has continued to be at the forefront of functional MRI innovation, having helped to pioneer real time fMRI, high-resolution fMRI, and functional connectivity mapping. Published by Elsevier Inc.
C1 [Bandettini, Peter A.] NIMH, Sect Funct Imaging Methods, Bethesda, MD 20892 USA.
[Bandettini, Peter A.] NIMH, Funct MRI Core Facil, Bethesda, MD USA.
RP Bandettini, PA (reprint author), NIMH, Sect Funct Imaging Methods, Bethesda, MD 20892 USA.
EM pab.neuroimage@gmail.com
FU NIH; NINDS; NIMH
FX I would like to thank Patricia Bandettini, Scott Hinks, Jim Hyde, and
Eric Wong for help in the proofreading of this document. The NIH
intramural programs, NINDS and NIMH, support Peter Bandettini.
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J9 NEUROIMAGE
JI Neuroimage
PD AUG 15
PY 2012
VL 62
IS 2
SI SI
BP 620
EP 631
DI 10.1016/j.neuroimage.2011.10.044
PG 12
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 973WK
UT WOS:000306390600008
PM 22044784
ER
PT J
AU van Gelderen, P
Duyn, JH
Ramsey, NF
Liu, G
Moonen, CTW
AF van Gelderen, P.
Duyn, J. H.
Ramsey, N. F.
Liu, G.
Moonen, C. T. W.
TI The PRESTO technique for fMRI
SO NEUROIMAGE
LA English
DT Review
DE Functional magnetic resonance imaging (fMRI); Blood oxygenation level
dependent (BOLD); contrast; PRESTO (Principles of Echo-Shifting with a
Train of Observation); Echo shifting
ID GRADIENT-RECALLED MRI; HUMAN VISUAL-CORTEX; FUNCTIONAL MRI; HUMAN BRAIN;
CONTRAST AGENT; LANGUAGE LATERALIZATION; TIME-SERIES; ECHO; SENSE; EPI
AB In the early days of BOLD fMRI, the acquisition of T-2* weighted data was greatly facilitated by rapid scan techniques such as EPI. The latter, however, was only available on a few MRI systems that were equipped with specialized hardware that allowed rapid switching of the imaging gradients. For this reason, soon after the invention of fMRI, the scan technique PRESTO was developed to make rapid T-2* weighted scanning available on standard clinical scanners. This method combined echo shifting, which allows for echo times longer than the sequence repetition time, with acquisition of multiple k-space lines per excitation. These two concepts were combined in order to achieve a method fast enough for fMRI, while maintaining a sufficiently long echo time for optimal contrast. PRESTO has been primarily used for 3D scanning, which minimized the contribution of large vessels due to inflow effects. Although PRESTO is still being used today, its appeal has lessened somewhat due to increased gradient performance of modern MRI scanners. Compared to 2D EPI, PRESTO may have somewhat reduced temporal stability, which is a disadvantage for fMRI that may not outweigh the advantage of reduced inflow effects provided by 3D scanning. In this overview, the history of the development of the PRESTO is presented, followed by a qualitative comparison with EPI. Published by Elsevier Inc.
C1 [van Gelderen, P.; Duyn, J. H.] NINDS, NIH, Adv Magnet Resonance Imaging sect, Lab Funct & Mol Imaging, Bethesda, MD 20892 USA.
[Ramsey, N. F.] Univ Med Ctr Utrecht, Div Neurosci, Rudolf Magnus Inst Neurosci, Utrecht, Netherlands.
[Liu, G.] Natl Inst Biomed Imaging & Bioengn, Div Appl Sci & Technol, Bethesda, MD USA.
[Moonen, C. T. W.] Univ Med Ctr Utrecht, Dept Radiol, Utrecht, Netherlands.
RP van Gelderen, P (reprint author), NINDS, NIH, Adv Magnet Resonance Imaging sect, Lab Funct & Mol Imaging, Bld 10,Rm B1 D-725,10 Ctr Dr, Bethesda, MD 20892 USA.
EM gelderen@nih.gov
RI Moonen, Chrit/K-4434-2016
OI Moonen, Chrit/0000-0001-5593-3121
FU National Institute of Neurological Disorders and Stroke, NIH
FX This work was funded (in part) by the intramural program of the National
Institute of Neurological Disorders and Stroke, NIH.
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SN 1053-8119
J9 NEUROIMAGE
JI Neuroimage
PD AUG 15
PY 2012
VL 62
IS 2
SI SI
BP 676
EP 681
DI 10.1016/j.neuroimage.2012.01.017
PG 6
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 973WK
UT WOS:000306390600017
PM 22245350
ER
PT J
AU Cox, RW
AF Cox, Robert W.
TI AFNI: What a long strange trip it's been
SO NEUROIMAGE
LA English
DT Review
DE Functional data analysis; 3D registration; FMRI group analysis; FMRI
connectivity; FMRI software
ID HUMAN BRAIN-FUNCTION; FUNCTIONAL MRI; FMRI
AB AFNI is an open source software package for the analysis and display of functional MRI data. It originated in 1994 to meet the specific needs of researchers at the Medical College of Wisconsin, in particular the mapping of activation maps to Talairach-Tournoux space, but has been expanded steadily since then into a wide-ranging set of tool for FMRI data analyses. AFNI was the first platform for real-time 3D functional activation and registration calculations. One of AFNI's main strengths is,its flexibility and transparency. In recent years, significant efforts have been made to increase the user-friendliness of AFNI's FMRI processing stream, with the introduction of "super-scripts" to setup the entire analysis, and graphical front-ends for these managers. Published by Elsevier Inc.
C1 NIMH, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
RP Cox, RW (reprint author), NIMH, NIH, Dept Hlth & Human Serv, 10 Ctr Dr, Room 1D80, Bethesda, MD 20892 USA.
EM robertcox@mail.nih.gov
FU NIMH; NINDS
FX Without the efforts of these people (and others), AFNI would not have
"grown up" as well has it has thank you all. The development of AFNI has
been supported over the years by the American people: when I was at MCW,
via grants from the NIMH and NINDS extramural programs, and currently
via the NIMH and NINDS intramural programs.
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PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1053-8119
J9 NEUROIMAGE
JI Neuroimage
PD AUG 15
PY 2012
VL 62
IS 2
SI SI
BP 743
EP 747
DI 10.1016/j.neuroimage.2011.08.056
PG 5
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 973WK
UT WOS:000306390600026
PM 21889996
ER
PT J
AU Saad, ZS
Reynolds, RC
AF Saad, Ziad S.
Reynolds, Richard C.
TI SUMA
SO NEUROIMAGE
LA English
DT Review
DE Cortical surface models; Cortical thickness; FMRI retinotopy; Surface
ROI drawing; Surface-based smoothing; Surface-based group analysis;
Interactive FMRI resting state analysis
ID SURFACE-BASED ANALYSIS; CORTICAL SURFACE; COORDINATE SYSTEM;
CEREBRAL-CORTEX; MRI; REGISTRATION; SOFTWARE
AB Surface-based brain imaging analysis offers the advantages of preserving the topology of cortical activation, increasing statistical power of group-level statistics, estimating cortical thickness, and visualizing with ease the pattern of activation across the whole cortex. SUMA is an open-source suite of programs for performing surface-based analysis and visualization. It was designed since its inception to allow for a fine control over the mapping between volume and surface domains, and for very fast and simultaneous display of multiple surface models and corresponding multitudes of datasets, all while maintaining a direct two-way link to volumetric data from which surface models and data originated. SUMA provides tools for performing spatial operations such as controlled smoothing, clustering, and interactive ROI drawing on folded surfaces in 3D, in addition to the various level-1 and level-2 FMRI statistics including FOR and FWE correction for multiple comparisons. In our contribution to this commemorative issue of Neuroimage we touch on the importance of surface-based analysis and provide a historic backdrop that motivated the creation of SUMA. We also highlight features that are particular to SUMA, notably the standardization procedure of meshes to greatly facilitate group-level analyses, and the ability to control SUMA's graphical interface from external programs making it possible to handle large collections of data with relative ease. Published by Elsevier Inc.
C1 [Saad, Ziad S.; Reynolds, Richard C.] NIMH, NIH, Bethesda, MD 20892 USA.
RP Saad, ZS (reprint author), NIMH, NIH, 10 Ctr DR,Room 1080, Bethesda, MD 20892 USA.
EM saadz@mail.nih.gov
FU NIMH of NIH; NINDS of NIH
FX Much of the utility and speed of SUMA (and for better or worse, the
first author's) is due to the leveraging of AFNI's libraries, interface,
and most importantly the vast and generous mind of AFNI's creator,
Robert W. Cox. The authors are particularly grateful to Michael S.
Beauchamp for feedback and support, and to all users with encouraging
messages and thoughtful suggestions. Credit is also due to Edgar A.
DeYoe whose early ideas for a good surface-mapping interface shaped many
of SUMA's features years later. This research was supported by the NIMH
and NINDS Intramural Research Programs of the NIH.
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J9 NEUROIMAGE
JI Neuroimage
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SI SI
BP 768
EP 773
DI 10.1016/j.neuroimage.2011.09.016
PG 6
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 973WK
UT WOS:000306390600030
PM 21945692
ER
PT J
AU Silva, AC
AF Silva, Afonso C.
TI Using manganese-enhanced MRI to understand BOLD
SO NEUROIMAGE
LA English
DT Review
DE Animal models; Blood-brain barrier; Brain; Cerebral blood flow;
Functional magnetic resonance imaging; Manganese; Neural activity
ID RESONANCE-IMAGING MEMRI; NUCLEAR-MAGNETIC-RESONANCE;
CEREBRAL-BLOOD-FLOW; RAT-BRAIN; FOREPAW STIMULATION; FUNCTIONAL MRI;
IN-VIVO; DEPENDENT CONTRAST; SENSORY STIMULATION; NEGATIVE RESPONSE
AB The 1990s were designated "The Decade of the Brain" by U.S. Congress, perhaps in great anticipation of the impact that functional neuroimaging techniques would have on advancing our understanding of how the brain is functionally organized. While it is impossible to overestimate the impact of functional MRI in neuroscience, many aspects of the blood oxygenation level-dependent (BOLD) contrast remain poorly understood, in great part due to the complex relationship between neural activity and hemodynamic changes. To better understand such relationship, it is important to probe neural activity independently. Manganese-enhanced MRI (MEMRI), when used to monitor neural activity, is a technique that uses the divalent manganese ion, Mn2+, as a surrogate measure of calcium influx. A major advantage of using Mn2+ as a functional marker is that the contrast obtained is directly related to the accumulation of the ion in excitable cells in an activity dependent manner. As such, the contrast in MEMRI is more directly related to neural activity then hemodynamic-based fMRI techniques. In the present work, the early conceptualization of MEMRI is reviewed, and the comparative experiments that have helped provide a better understanding of the spatial specificity of BOLD signal changes in the cortex is discussed. Published by Elsevier Inc.
C1 NINDS, Cerebral Microcirculat Unit, NIH, Lab Funct & Mol Imaging, Bethesda, MD 20892 USA.
RP Silva, AC (reprint author), NINDS, Cerebral Microcirculat Unit, NIH, Lab Funct & Mol Imaging, 10 Ctr Dr,MSC 1065,Bldg 10,Room B1D106, Bethesda, MD 20892 USA.
EM SilvaA@ninds.nih.gov
FU Intramural Research Program of the NIH, NINDS
FX I am most grateful to Alan P. Koretsky for critical reading of the
manuscript. This research was supported by the Intramural Research
Program of the NIH, NINDS.
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J9 NEUROIMAGE
JI Neuroimage
PD AUG 15
PY 2012
VL 62
IS 2
SI SI
BP 1009
EP 1013
DI 10.1016/j.neuroimage.2012.01.008
PG 5
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 973WK
UT WOS:000306390600059
PM 22245640
ER
PT J
AU Handwerker, DA
Gonzalez-Castillo, J
D'Esposito, M
Bandettini, PA
AF Handwerker, Daniel A.
Gonzalez-Castillo, Javier
D'Esposito, Mark
Bandettini, Peter A.
TI The continuing challenge of understanding and modeling hemodynamic
variation in fMRI
SO NEUROIMAGE
LA English
DT Review
DE BOLD; fMRI; Hemodynamic response; Population studies; Regional
variation; Blood vessels
ID CEREBRAL-BLOOD-FLOW; VISUAL BOLD RESPONSE; EVENT-RELATED FMRI;
FUNCTIONAL MRI; HUMAN BRAIN; OXYGEN-METABOLISM; BASE-LINE; STIMULATION;
ACTIVATION; CAFFEINE
AB Interpretation of fMRI data depends on our ability to understand or model the shape of the hemodynamic response (HR) to a neural event. Although the HR has been studied almost since the beginning of fMRI, we are still far from having robust methods to account for the full range of known HR variation in typical fMRI analyses. This paper reviews how the authors and others contributed to our understanding of HR variation. We present an overview of studies that describe HR variation across voxels, healthy volunteers, populations, and dietary or pharmaceutical modulations. We also describe efforts to minimize the effects of HR variation in intrasubject, group, population, and connectivity analyses and the limits of these methods. Published by Elsevier Inc.
C1 [Handwerker, Daniel A.; Gonzalez-Castillo, Javier; Bandettini, Peter A.] NIMH, Lab Brain & Cognit, Sect Funct Imaging Methods, Bethesda, MD 20814 USA.
[Bandettini, Peter A.] NIMH, Funct MRI Facil, Bethesda, MD 20892 USA.
[D'Esposito, Mark] Univ Calif Berkeley, Helen Wills Neurosci Inst, Berkeley, CA 94720 USA.
[D'Esposito, Mark] Univ Calif Berkeley, Dept Psychol, Berkeley, CA 94720 USA.
RP Handwerker, DA (reprint author), Bldg 10,Rm 1080,10 Ctr Dr MSC 1148, Bethesda, MD 20892 USA.
EM handwerkerd@mail.nih.gov
OI Gonzalez-Castillo, Javier/0000-0002-6520-5125
FU NIMH Intramural research program
FX Supported by the NIMH Intramural research program. Carlton Chu helped
make sure the DCM analyses were properly run.
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J9 NEUROIMAGE
JI Neuroimage
PD AUG 15
PY 2012
VL 62
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SI SI
BP 1017
EP 1023
DI 10.1016/j.neuroimage.2012.02.015
PG 7
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 973WK
UT WOS:000306390600061
PM 22366081
ER
PT J
AU Koretsky, AP
AF Koretsky, Alan P.
TI Is there a path beyond BOLD? Molecular imaging of brain function
SO NEUROIMAGE
LA English
DT Review
DE Manganese enhanced MRI; MRI calcium indicators; MRI gene expression
reporters; MRI detection of neurotransmitters; MRI detection of membrane
potential
ID MANGANESE-ENHANCED MRI; NUCLEAR-MAGNETIC-RESONANCE;
CENTRAL-NERVOUS-SYSTEM; IN-VIVO DETECTION; GENE-EXPRESSION; CONTRAST
AGENT; CREATINE-KINASE; BETA-GALACTOSIDASE; REPORTER GENE; RAT-BRAIN
AB The dependence of BOLD on neuro-vascular coupling leaves it many biological steps removed from direct monitoring of neural function. MRI based approaches have been developed aimed at reporting more directly on brain function. These include: manganese enhanced MRI as a surrogate for calcium ion influx; agents responsive to calcium concentrations; approaches to measure membrane potential; agents to measure neurotransmitters; and strategies to measure gene expression. This work has led to clever design of molecular imaging tools and many contributions to studies of brain function in animal models. However, a robust approach that has potential to get MRI closer to neurons in the human brain has not yet emerged. (C) 2012 Published by Elsevier Inc.
C1 NINDS, LFMI, NIH, Bethesda, MD 20892 USA.
RP Koretsky, AP (reprint author), NINDS, LFMI, NIH, Bldg 10,Rm B1D728,10 Ctr Dr, Bethesda, MD 20892 USA.
EM koretskya@ninds.nih.gov
RI Koretsky, Alan/C-7940-2015
OI Koretsky, Alan/0000-0002-8085-4756
FU National Institute of Neurological Disorders and Stroke, NIH
FX Alan Koretsky is supported by the intramural research program of the
National Institute of Neurological Disorders and Stroke, NIH. The author
acknowledges the kind invitation from Peter Bandettini to write this
article and thanks Afonso Silva for encouragement and comments.
NR 139
TC 16
Z9 16
U1 1
U2 28
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1053-8119
J9 NEUROIMAGE
JI Neuroimage
PD AUG 15
PY 2012
VL 62
IS 2
SI SI
BP 1208
EP 1215
DI 10.1016/j.neuroimage.2012.02.076
PG 8
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 973WK
UT WOS:000306390600088
PM 22406355
ER
PT J
AU Duyn, JH
AF Duyn, Jeff H.
TI The future of ultra-high field MRI and fMRI for study of the human brain
SO NEUROIMAGE
LA English
DT Review
DE High field MRI; Magnet technology; RF coils; Resolution; Contrast; Brain
function; Brain structure; Myelin; Cortex
ID HIGH-RESOLUTION MRI; TO-NOISE RATIO; VIVO H-1-NMR SPECTROSCOPY; HIGH
MAGNETIC-FIELD; ARRAY HEAD COIL; IN-VIVO; MULTIPLE-SCLEROSIS;
WHITE-MATTER; 3 TESLA; ORIENTATION COLUMNS
AB MRI and fMRI have been used for about three and two decades respectively and much has changed over this time period, both in the quality of the data and in the range of applications for studying the brain. Apart from resolution improvements from around 4 mm in the early days to below 0.5 mm with modern technology, novel uses of contrast have led to the ability to sensitize images to some of the brain's structural properties at the cellular scale as well as study the localization and organization of brain function at the level of cortical columns. These developments have in part been facilitated by a continuing drive to increase the magnetic field strength. Will the next few decades see similar improvements? Here we will discuss current state of high field MRI, expected further increases in field strength, and improvements expected with these increases. (C) 2011 Elsevier Inc. All rights reserved.
C1 NINDS, Adv MRI Sect, Lab Funct & Mol Imaging, NIH, Bethesda, MD 20892 USA.
RP Duyn, JH (reprint author), NINDS, Adv MRI Sect, Lab Funct & Mol Imaging, NIH, Bldg 10,Room B1D724,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM jhd@helix.nih.gov
FU National Institute of Neurological Disorders and Stroke, National
Institutes of Health
FX Alan Koretsky and Peter van Gelderen of the Laboratory of Functional and
Molecular imaging at NIH are acknowledged for helpful discussions and
suggestions. This research was supported by the Intramural Research
Program of the National Institute of Neurological Disorders and Stroke,
National Institutes of Health.
NR 104
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Z9 59
U1 3
U2 42
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1053-8119
J9 NEUROIMAGE
JI Neuroimage
PD AUG 15
PY 2012
VL 62
IS 2
SI SI
BP 1241
EP 1248
DI 10.1016/j.neuroimage.2011.10.065
PG 8
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 973WK
UT WOS:000306390600093
PM 22063093
ER
PT J
AU Del Brutto, OH
Nash, TE
Garcia, HH
AF Del Brutto, Oscar H.
Nash, Theodore E.
Garcia, Hector H.
TI Cysticerci-related single parenchymal brain enhancing lesions in
non-endemic countries
SO JOURNAL OF THE NEUROLOGICAL SCIENCES
LA English
DT Article
DE Cysticercosis; Neurocysticercosis; Single cysticercus granuloma
ID TAENIA-SOLIUM; SOLITARY NEUROCYSTICERCOSIS; FOLLOW-UP; SEIZURES;
GRANULOMA; DIAGNOSIS; EDEMA; FEATURES; MASS; UK
AB Objective: Review of case reports and case series of patients with single cysticercus granulomas in non-endemic countries to determine the characteristics of this form of neurocysticercosis in these regions.
Methods: MEDLINE and manual search of patients with single cysticercus granulomas diagnosed in non-endemic countries from 1991 to 2011. Abstracted data included: demographic profile, clinical manifestations, form of neurocysticercosis, and whether the disease occurred in immigrants, international travelers, or citizens from non-endemic countries who had never been abroad.
Results: A total of 77 patients were found. Of these, 61 (79%) were diagnosed since the year 2000. Thirty-four patients (44%) patients were immigrants from endemic countries, 18 (23%) were international travelers returning from disease-endemic areas, and the remaining 25 (33%) were citizens from non-endemic countries who had never been abroad. Most immigrants and international travelers became symptomatic two or more years after returning home. Countries with the most reported patients were Kuwait (n = 18), UK (n = 11), Australia (n = 8), USA (n = 7), Japan (n = 6), and Israel (n = 5).
Conclusions: A single cerebral cysticercus granuloma in a non-endemic country is not a rare event. As seen in endemic regions, these cases have a good prognosis although more surgical procedures are performed in non-endemic countries, likely reflecting a decrease of diagnostic suspicion for cysticercosis and an increased availability of surgical options. The mean age of the reported cases was 25 years, and immigrants most often developed the disease greater than two years after arrival into a non-endemic area, suggesting a significant delay between infection and symptoms. However, some may have been infected and developed the disease while residing in non-endemic countries. (C) 2012 Elsevier B.V. All rights reserved.
C1 [Del Brutto, Oscar H.] Hosp Clin Kennedy, Dept Neurol Sci, Guayaquil, Ecuador.
[Nash, Theodore E.] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
[Garcia, Hector H.] Univ Peruana Cayetano Heredia, Ctr Global Hlth, Lima, Peru.
[Garcia, Hector H.] Univ Peruana Cayetano Heredia, Dept Microbiol, Sch Sci, Lima, Peru.
[Garcia, Hector H.] Inst Nacl Ciencias Neurol, Cysticercosis Unit, Lima, Peru.
RP Del Brutto, OH (reprint author), Air Ctr 3542,POB 522970, Miami, FL 33152 USA.
EM oscardelbrutto@hotmail.com
FU Division of Intramural Research, National Institutes of Allergy and
Infectious Diseases; Wellcome Trust
FX Funding for this work was provided in part by the Division of Intramural
Research, National Institutes of Allergy and Infectious Diseases (Dr.
Nash). Dr. Garcia is supported by a Wellcome Trust International Senior
Fellowship in Public Health and Tropical Medicine.
NR 70
TC 10
Z9 10
U1 0
U2 2
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0022-510X
J9 J NEUROL SCI
JI J. Neurol. Sci.
PD AUG 15
PY 2012
VL 319
IS 1-2
BP 32
EP 36
DI 10.1016/j.jns.2012.05.027
PG 5
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 971ZS
UT WOS:000306246900007
PM 22658897
ER
PT J
AU Campa, D
Butterbach, K
Slager, SL
Skibola, CF
de Sanjose, S
Benavente, Y
Becker, N
Foretova, L
Maynadie, M
Cocco, P
Staines, A
Kaaks, R
Boffetta, P
Brennan, P
Conde, L
Bracci, PM
Caporaso, NE
Strom, SS
Camp, NJ
Cerhan, JR
Canzian, F
Nieters, A
AF Campa, Daniele
Butterbach, Katja
Slager, Susan L.
Skibola, Christine F.
de Sanjose, Silvia
Benavente, Yolanda
Becker, Nikolaus
Foretova, Lenka
Maynadie, Marc
Cocco, Pierluigi
Staines, Anthony
Kaaks, Rudolf
Boffetta, Paolo
Brennan, Paul
Conde, Lucia
Bracci, Paige M.
Caporaso, Neil E.
Strom, Sara S.
Camp, Nicola J.
Cerhan, James R.
Canzian, Federico
Nieters, Alexandra
CA GEC Consortium
TI A comprehensive study of polymorphisms in the ABCB1, ABCC2, ABCG2, NR1I2
genes and lymphoma risk
SO INTERNATIONAL JOURNAL OF CANCER
LA English
DT Article
DE lymphoma; multidrug resistance 1; multidrug resistance protein 2; breast
cancer resistance protein; pregnane x receptor
ID SINGLE NUCLEOTIDE POLYMORPHISMS; ACUTE LYMPHOBLASTIC-LEUKEMIA;
GENOME-WIDE ASSOCIATION; NON-HODGKIN-LYMPHOMA; CHRONIC
LYMPHOCYTIC-LEUKEMIA; CANCER RESISTANCE PROTEIN; B-CELL LYMPHOMA; C421A
POLYMORPHISM; EPIDEMIOLOGY CONSORTIUM; TISSUE DEFENSE
AB Owing to their role in controlling the efflux of toxic compounds, transporters are central players in the process of detoxification and elimination of xenobiotics, which in turn is related to cancer risk. Among these transporters, ATP-binding cassette B1/multidrug resistance 1 (ABCB1/MDR1), ABCC2/multidrug resistance protein 2 (MRP2) and ABCG2/breast cancer resistance protein (BCRP) affect susceptibility to many hematopoietic malignancies. The maintenance of regulated expression of these transporters is governed through the activation of intracellular xenosensors like the nuclear receptor 1I2/pregnane X receptor (NR1I2/PXR). SNPs in genes encoding these regulators have also been implicated in the risk of several cancers. Using a tagging approach, we tested the hypothesis that common polymorphisms in the transporter genes ABCB1, ABCC2, ABCG2 and the regulator gene NR1I2 could be implicated in lymphoma risk. We selected 68 SNPs in the four genes, and we genotyped them in 1,481 lymphoma cases and 1,491 controls of the European casecontrol study (EpiLymph) using the Illumina GoldenGate (TM) assay technology. Carriers of the SNP rs6857600 minor allele in ABCG2 was associated with a decrease in risk of B-cell lymphoma (B-NHL) overall (p < 0.001). Furthermore, a decreased risk of chronic lymphocytic leukemia (CLL) was associated with the ABCG2 rs2231142 variant (p = 0.0004), which could be replicated in an independent population. These results suggest a role for this gene in B-NHL susceptibility, especially for CLL.
C1 [Nieters, Alexandra] Univ Med Ctr, Ctr Chron Immunodeficiency, D-79106 Freiburg, Germany.
[Campa, Daniele; Canzian, Federico] German Canc Res Ctr, Genom Epidemiol Grp, Heidelberg, Germany.
[Butterbach, Katja; Becker, Nikolaus; Kaaks, Rudolf] German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany.
[Slager, Susan L.] Mayo Clin, Coll Med, Div Biomed Stat & Informat, Rochester, MN USA.
[Skibola, Christine F.; Conde, Lucia] Univ Calif Berkeley, Sch Publ Hlth, Div Environm Hlth Sci, Berkeley, CA 94720 USA.
[de Sanjose, Silvia; Benavente, Yolanda] Catalan Inst Oncol, Unit Infect & Canc, Barcelona, Spain.
[de Sanjose, Silvia; Benavente, Yolanda] CIBERESP, Madrid, Spain.
[Foretova, Lenka] Masaryk Mem Canc Inst, Brno, Czech Republic.
[Maynadie, Marc] Univ Burgundy, CHU Dijon, EA 4184, Serv Hematol Biol, Dijon, France.
[Cocco, Pierluigi] Univ Cagliari, Occupat Hlth Sect, Dept Publ Hlth, Cagliari, Italy.
[Staines, Anthony] Dublin City Univ, Sch Nursing, Dublin 9, Ireland.
[Boffetta, Paolo] Mt Sinai Sch Med, Tisch Canc Inst, New York, NY USA.
[Boffetta, Paolo] Mt Sinai Sch Med, Inst Translat Epidemiol, New York, NY USA.
[Boffetta, Paolo] Int Prevent Res Inst, Lyon, France.
[Brennan, Paul] Int Agcy Res Canc, F-69372 Lyon, France.
[Bracci, Paige M.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA.
[Caporaso, Neil E.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Strom, Sara S.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Camp, Nicola J.] Univ Utah, Sch Med, Salt Lake City, UT USA.
[Cerhan, James R.] Mayo Clin, Coll Med, Div Epidemiol, Rochester, MN USA.
[Nieters, Alexandra] Univ Med Ctr, Inst Med Biostat & Med Informat, D-79106 Freiburg, Germany.
[Nieters, Alexandra] Univ Freiburg, D-79106 Freiburg, Germany.
RP Nieters, A (reprint author), Univ Med Ctr, Ctr Chron Immunodeficiency, Breisacher Str 117, D-79106 Freiburg, Germany.
EM alexandra.nieters@uniklinik-freiburg.de
RI Conde, Lucia/D-9295-2011; de Sanjose Llongueras, Silvia/H-6339-2014;
Benavente, Yolanda/H-9810-2014; Campa, Daniele/K-1617-2016;
OI Campa, Daniele/0000-0003-3220-9944; Cerhan, James/0000-0002-7482-178X;
Staines, Anthony/0000-0001-9161-1357
FU German Jose Carreras Leukemia Foundation [DJCLS_R04/08]; EC
[QLK4-CT-2000-00422, FP6-2003-FOOD-2-B]; Federal Office for Radiation
Protection (Germany) [StSch4261, StSch4420]; Spanish Ministry of Health
grants CIBERESP (Spain) [06/02/0073, FIS 08-1555 1, Marato V3 (051210)];
La Fondation de France; Compagnia di San Paolo di Torino, Programma
Oncologia; Health Research Board, Ireland
FX Grant sponsor: German Jose Carreras Leukemia Foundation; Grant number:
DJCLS_R04/08; Grant sponsor: EC 5th Framework Program Quality of Life;
Grant number: QLK4-CT-2000-00422; Grant sponsor: EC 6th Framework
Program; Grant number: FP6-2003-FOOD-2-B; Grant sponsor: Federal Office
for Radiation Protection; Grant numbers: StSch4261, StSch4420 (Germany);
Grant sponsor: Spanish Ministry of Health grants CIBERESP; Grant
numbers: 06/02/0073, FIS 08-1555 1 and Marato V3 (051210) (Spain); Grant
sponsor: La Fondation de France; Grant sponsor: Compagnia di San Paolo
di Torino, Programma Oncologia; Grant sponsor: Health Research Board,
Ireland starD.C. and K.B. contributed equally to this work.
NR 50
TC 12
Z9 12
U1 0
U2 8
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0020-7136
J9 INT J CANCER
JI Int. J. Cancer
PD AUG 15
PY 2012
VL 131
IS 4
BP 803
EP 812
DI 10.1002/ijc.26436
PG 10
WC Oncology
SC Oncology
GA 961GD
UT WOS:000305451300031
PM 21918980
ER
PT J
AU Yang, HP
Trabert, B
Murphy, MA
Sherman, ME
Sampson, JN
Brinton, LA
Hartge, P
Hollenbeck, A
Park, Y
Wentzensen, N
AF Yang, Hannah P.
Trabert, Britton
Murphy, Megan A.
Sherman, Mark E.
Sampson, Joshua N.
Brinton, Louise A.
Hartge, Patricia
Hollenbeck, Albert
Park, Yikyung
Wentzensen, Nicolas
TI Ovarian cancer risk factors by histologic subtypes in the NIH-AARP diet
and health study
SO INTERNATIONAL JOURNAL OF CANCER
LA English
DT Article
DE reproductive factors; non-reproductive factors; histology; ovarian
cancer; prospective study
ID BODY-MASS INDEX; FALLOPIAN-TUBE; CIGARETTE-SMOKING; ENDOMETRIAL CANCER;
GENE-EXPRESSION; POSTMENOPAUSAL WOMEN; COLORECTAL-CANCER; POOLED
ANALYSIS; CARCINOMA; CARCINOGENESIS
AB Data suggest that risk factors for ovarian carcinoma vary by histologic type, but findings are inconsistent. We prospectively evaluated risk factors by histological subtypes of incident ovarian cancer (n = 849) in a cohort of 169,391 women in the NIH-AARP Diet and Health Study. We constructed Cox models of individual exposures by comparing case subtypes to the entire non-case group and assessed p-heterogeneity in casecase comparisons using serous as the reference category. Substantial risk differences between histologic subtypes were observed for menopausal hormone therapy (MHT) use, oral contraceptive (OC) use, parity and body mass index (p-heterogeneity = 0.01, 0.03, 0.05, 0.03, respectively). MHT users were at increased risk for all histologic subtypes except for mucinous carcinomas, where risk was reduced (relative risk (RR) = 0.37; 95% confidence interval (CI): 0.18, 0.80). OC users were only at significantly decreased risk for serous cancers (RR = 0.69; 95% CI: 0.55, 0.85). Although parity was inversely associated with risk of all subtypes, the RRs ranged from 0.28 (clear cell) to 0.83 (serous). Obesity was a significant risk factor only for endometrioid cancers (RR = 1.64; 95% CI: 1.00, 2.70). Our findings support a link between etiological factors and histological heterogeneity in ovarian carcinoma.
C1 [Yang, Hannah P.; Trabert, Britton; Murphy, Megan A.; Sherman, Mark E.; Brinton, Louise A.; Wentzensen, Nicolas] NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv,NIH, Rockville, MD 20852 USA.
[Sampson, Joshua N.] NCI, Biostat Branch, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv,NIH, Rockville, MD 20852 USA.
[Hollenbeck, Albert] AARP, Washington, DC USA.
[Park, Yikyung] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv,NIH, Rockville, MD 20852 USA.
RP Yang, HP (reprint author), NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv,NIH, 6120 Execut Blvd,EPS-5102, Rockville, MD 20852 USA.
EM yanghan@mail.nih.gov
RI Brinton, Louise/G-7486-2015; Trabert, Britton/F-8051-2015;
OI Brinton, Louise/0000-0003-3853-8562; Park, Yikyung/0000-0002-6281-489X
FU Intramural Research Program of the NIH; National Cancer Institute; NIH
[5 T32 CA09001-35]
FX Grant sponsors: Intramural Research Program of the NIH, National Cancer
Institute, Grant sponsor: NIH; Cancer incidence data from the Atlanta
metropolitan area were collected by the Georgia Center for Cancer
Statistics, Department of Epidemiology, Rollins School of Public Health,
Emory University. Cancer incidence data from California were collected
by the California Department of Health Services, Cancer Surveillance
Section. Cancer incidence data from the Detroit metropolitan area were
collected by the Michigan Cancer Surveillance Program, Community Health
Administration, State of Michigan. The Florida cancer incidence data
used in this report were collected by the Florida Cancer Data System
under contract to the Department of Health (DOH). The views expressed
herein are solely those of the authors and do not necessarily reflect
those of the contractor or DOH. Cancer incidence data from Louisiana
were collected by the Louisiana Tumor Registry, Louisiana State
University Medical Center in New Orleans. Cancer incidence data from New
Jersey were collected by the New Jersey State Cancer Registry, Cancer
Epidemiology Services, New Jersey State Department of Health and Senior
Services. Cancer incidence data from North Carolina were collected by
the North Carolina Central Cancer Registry. Cancer incidence data from
Pennsylvania were supplied by the Division of Health Statistics and
Research, Pennsylvania Department of Health, Harrisburg, Pennsylvania.
The Pennsylvania Department of Health specifically disclaims
responsibility for any analyses, interpretations or conclusions. Cancer
incidence data from Arizona were collected by the Arizona Cancer
Registry, Division of Public Health Services, Arizona Department of
Health Services. Cancer incidence data from Texas were collected by the
Texas Cancer Registry, Cancer Epidemiology and Surveillance Branch,
Texas Department of State Health Services. Authors are indebted to the
participants in the NIH-AARP Diet and Health Study for their outstanding
cooperation. Authors thank Sigurd Hermansen and Kerry Grace Morrissey
from Westat for study outcomes ascertainment and management and Leslie
Carroll at Information Management Services for data support and
analysis. Megan A Murphy is supported in part by training grant NIH 5
T32 CA09001-35. In memory of Dr. Arthur Schatzkin, visionary
investigator who founded the NIH-AARP Diet and Health Study.
NR 51
TC 35
Z9 35
U1 0
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0020-7136
J9 INT J CANCER
JI Int. J. Cancer
PD AUG 15
PY 2012
VL 131
IS 4
BP 938
EP 948
DI 10.1002/ijc.26469
PG 11
WC Oncology
SC Oncology
GA 961GD
UT WOS:000305451300045
PM 21960414
ER
PT J
AU Tatokoro, M
Koga, F
Yoshida, S
Kawakami, S
Fujii, Y
Neckers, L
Kihara, K
AF Tatokoro, Manabu
Koga, Fumitaka
Yoshida, Soichiro
Kawakami, Satoru
Fujii, Yasuhisa
Neckers, Len
Kihara, Kazunori
TI Potential role of Hsp90 inhibitors in overcoming cisplatin resistance of
bladder cancer-initiating cells
SO INTERNATIONAL JOURNAL OF CANCER
LA English
DT Article
DE bladder cancer; tumor-initiating cell; Hsp90 inhibitors; cisplatin
resistance
ID SHOCK-PROTEIN 90; STEM-CELLS; UROTHELIAL CARCINOMA; GROWTH-FACTOR;
TUMOR-GROWTH; IDENTIFICATION; HYALURONAN; APOPTOSIS; LEUKEMIA; INVASION
AB For metastatic bladder cancer patients, systemic cisplatin (CDDP)-based combination chemotherapy is the first-line choice of treatment. Although up to 70% of advanced bladder cancer patients initially show good tumor response to this form of combination chemotherapy, over 90% of good responders relapse and eventually die of the disease. According to the cancer stem cell theory, this phenomenon is attributable to the re-growth of bladder cancer-initiating cells (BCICs) that have survived chemotherapy. In this study, the authors have isolated BCICs from cultured human bladder cancer cells to analyze their sensitivity to CDDP and to investigate whether heat-shock protein 90 (Hsp90) inhibitors potentiate the cytotoxicity of CDDP on BCICs. First, the authors have confirmed that a CD44+ subpopulation of 5637 cells met the requirements to be considered tumor-initiating cells. These BCICs were more resistant to CDDP and exhibited more activity in the Akt and ERK oncogenic signaling pathways when compared with their CD44- counterparts. The Hsp90 inhibitor 17-(dimethylaminoethylamino)-17-demethoxygeldanamycin (17-DMAG), which simultaneously inactivated both Akt and ERK signaling at noncytocidal concentrations, synergistically potentiated the cytotoxicity of CDDP against BCICs by enhancing CDDP-induced apoptosis in vitro. The potentiating effect of 17-DMAG was more effective than a combination of the two inhibitors specific for the Akt and ERK pathways. Finally, the authors have confirmed that, though human BCIC xenografts exhibited resistance to a single administration of CDDP and the Hsp90 inhibitor 17-(allylamino)-17-demethoxygeldanamycin (17-AAG), 17-AAG sensitized them to CDDP in a mouse model. These data encourage clinical trials of Hsp90 inhibitors as they may improve therapeutic outcomes of CDDP-based combination chemotherapy against advanced bladder cancer.
C1 [Tatokoro, Manabu; Koga, Fumitaka; Yoshida, Soichiro; Kawakami, Satoru; Fujii, Yasuhisa; Kihara, Kazunori] Tokyo Med & Dent Univ, Grad Sch, Dept Urol, Bunkyo Ku, Tokyo 1138519, Japan.
[Neckers, Len] NCI, Urol Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Koga, F (reprint author), Tokyo Med & Dent Univ, Grad Sch, Dept Urol, Bunkyo Ku, 1-5-45 Yushima, Tokyo 1138519, Japan.
EM f-koga.uro@tmd.ac.jp
FU Ministry of Education, Culture, Sports, Science and Technology of Japan
[23791744, 23501266]
FX This work was supported, in part, by grants-in-aids for Scientific
research 23791744 (Manabu Tatokoro), 23501266 (Fumitaka Koga), from the
Ministry of Education, Culture, Sports, Science and Technology of Japan.
NR 50
TC 28
Z9 30
U1 0
U2 9
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0020-7136
J9 INT J CANCER
JI Int. J. Cancer
PD AUG 15
PY 2012
VL 131
IS 4
BP 987
EP 996
DI 10.1002/ijc.26475
PG 10
WC Oncology
SC Oncology
GA 961GD
UT WOS:000305451300050
PM 21964864
ER
PT J
AU Gunter, MJ
Schaub, JA
Xue, XN
Freedman, ND
Gaudet, MM
Rohan, TE
Hollenbeck, AR
Sinha, R
AF Gunter, Marc J.
Schaub, Jennifer A.
Xue, Xiaonan
Freedman, Neal D.
Gaudet, Mia M.
Rohan, Thomas E.
Hollenbeck, Albert R.
Sinha, Rashmi
TI A prospective investigation of coffee drinking and endometrial cancer
incidence
SO INTERNATIONAL JOURNAL OF CANCER
LA English
DT Article
DE coffee; endometrial cancer; chemoprevention
ID CIGARETTE-SMOKING; RISK; INSULIN; GROWTH; CONSUMPTION; CAFFEINE; COHORT;
WOMEN
AB Coffee drinking may be associated with reduced risk of endometrial cancer; however, prospective data are limited. Further, it is not clear whether any association between coffee and endometrial cancer differs according to coffee caffeine content. The association of coffee drinking with incidence of endometrial cancer was evaluated among 226,732 women, aged 5071, enrolled in the NIH-AARP Diet and Health Study who completed a baseline epidemiologic questionnaire. Following a mean 9.3 years of follow-up, data were available for 1,486 incident endometrial cancer cases. Cox proportional hazards models were used to estimate associations of coffee with endometrial cancer incidence. Sub-group analyses were performed according to smoking status, hormone therapy use (HT) and body habitus. Coffee drinking was inversely related to incidence of endometrial cancer (hazard ratio [HR] comparing drinking of >3 cups/day versus no cups = 0.64, 95% CI, 0.510.80; Ptrend = 0.0004). The association of coffee with endometrial cancer risk was apparent for consumption of both regular (HR per cup = 0.90, 95% CI, 0.860.95) and decaffeinated coffee (HR per cup = 0.93, 95% CI, 0.870.99). The relation of coffee with endometrial cancer incidence varied significantly by HT use (Pinteraction = 0.03) with an association only apparent among HT-never users (HR comparing drinking >3 cups/day versus no cups = 0.54, 95% CI, 0.410.72; Ptrend = 0.0005). Endometrial cancer incidence appears to be reduced among women that habitually drink coffee, an association that does not differ according to caffeine content.
C1 [Gunter, Marc J.; Schaub, Jennifer A.; Xue, Xiaonan; Rohan, Thomas E.] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Dept Epidemiol & Biostat, London W2 1PG, England.
[Gunter, Marc J.] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, New York, NY USA.
[Freedman, Neal D.; Sinha, Rashmi] NCI, Div Canc Epidemiol & Genet, NIH, Rockville, MD USA.
[Gaudet, Mia M.] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA.
[Hollenbeck, Albert R.] AARP, Washington, DC USA.
RP Gunter, MJ (reprint author), Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Dept Epidemiol & Biostat, Norfolk Pl, London W2 1PG, England.
EM m.gunter@imperial.ac.uk
RI Sinha, Rashmi/G-7446-2015; Freedman, Neal/B-9741-2015;
OI Sinha, Rashmi/0000-0002-2466-7462; Freedman, Neal/0000-0003-0074-1098;
Schaub, Jennifer/0000-0001-8788-239X
FU Intramural Research Program of National Cancer Institute, NIH; Florida
Cancer Data System
FX Grant sponsor: Intramural Research Program of National Cancer Institute,
NIH; We thank the participants in the NIH-AARP Diet and Health Study for
their outstanding cooperation, Adam Risch from Information Management
Services for data support and analysis, Sigurd Hermansen and Kerry Grace
Morrissey from Westat for study outcome ascertainment and management.
Cancer incidence data from the Atlanta metropolitan area were collected
by Georgia Center for Cancer Statistics, Department of Epidemiology,
Rollins School of Public Health, Emory University. Cancer incidence data
from California were collected by California Department of Health
Services, Cancer Surveillance Section. Cancer incidence data from the
Detroit metropolitan area were collected by Michigan Cancer Surveillance
Program, Community Health Administration, State of Michigan. The Florida
cancer incidence data used in this report were collected by Florida
Cancer Data System under contract to Department of Health (DOH). The
views expressed herein are solely those of the authors and do not
necessarily reflect those of the contractor or DOH. Cancer incidence
data from Louisiana were collected by Louisiana Tumor Registry,
Louisiana State University Medical Center in New Orleans. Cancer
incidence data from New Jersey were collected by New Jersey State Cancer
Registry, Cancer Epidemiology Services, New Jersey State Department of
Health and Senior Services. Cancer incidence data from North Carolina
were collected by North Carolina Central Cancer Registry. Cancer
incidence data from Pennsylvania were supplied by Division of Health
Statistics and Research, Pennsylvania Department of Health, Harrisburg,
Pennsylvania. The Pennsylvania Department of Health specifically
disclaims responsibility for any analyses, interpretations, or
conclusions.
NR 18
TC 18
Z9 19
U1 1
U2 13
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0020-7136
J9 INT J CANCER
JI Int. J. Cancer
PD AUG 15
PY 2012
VL 131
IS 4
BP E530
EP E536
DI 10.1002/ijc.26482
PG 7
WC Oncology
SC Oncology
GA 961GD
UT WOS:000305451300020
PM 22021096
ER
PT J
AU Becker, D
Sfakianakis, I
Krupp, M
Staib, F
Gerhold-Ay, A
Victor, A
Binder, H
Blettner, M
Maass, T
Thorgeirsson, S
Galle, PR
Teufel, A
AF Becker, Diana
Sfakianakis, Ioannis
Krupp, Markus
Staib, Frank
Gerhold-Ay, Aslihan
Victor, Anja
Binder, Harald
Blettner, Maria
Maass, Thorsten
Thorgeirsson, Snorri
Galle, Peter R.
Teufel, Andreas
TI Genetic signatures shared in embryonic liver development and liver
cancer define prognostically relevant subgroups in HCC
SO MOLECULAR CANCER
LA English
DT Article
ID HEPATOCELLULAR-CARCINOMA CELLS; BETA-CATENIN; TRANSCRIPTION FACTORS;
PROGENITOR CELLS; EXPRESSION; PROLIFERATION; MORPHOGENESIS; GROWTH;
DIFFERENTIATION; EPIDEMIOLOGY
AB Multiple activations of individual genes during embryonic liver and HCC development have repeatedly prompted speculations about conserved embryonic signatures driving cancer development. Recently, the emerging discussion on cancer stem cells and the appreciation that generally tumors may develop from progenitor cells of diverse stages of cellular differentiation has shed increasing light on the overlapping genetic signatures between embryonic liver development and HCC. However there is still a lack of systematic studies investigating this area. We therefore performed a comprehensive analysis of differentially regulated genetic signaling pathways in embryonic and liver cancer development and investigated their biological relevance.
Genetic signaling pathways were investigated on several publically available genome wide microarray experiments on liver development and HCC. Differentially expressed genes were investigated for pathway enrichment or underrepresentation compared to KEGG annotated pathways by Fisher exact evaluation. The comparative analysis of enrichment and under representation of differentially regulated genes in liver development and HCC demonstrated a significant overlap between multiple pathways. Most strikingly we demonstrated a significant overlap not only in pathways expected to be relevant to both conditions such as cell cycle or apoptosis but also metabolic pathways associated with carbohydrate and lipid metabolism. Furthermore, we demonstrated the clinical significance of these findings as unsupervised clustering of HCC patients on the basis of these metabolic pathways displayed significant differences in survival.
These results indicate that liver development and liver cancer share similar alterations in multiple genetic signaling pathways. Several pathways with markedly similar patterns of enrichment or underrepresentation of various regulated genes between liver development and HCC are of prognostic relevance in HCC. In particular, the metabolic pathways were identified as novel prognostically relevant players in HCC development.
C1 [Becker, Diana; Sfakianakis, Ioannis; Krupp, Markus; Staib, Frank; Maass, Thorsten; Galle, Peter R.; Teufel, Andreas] Johannes Gutenberg Univ Mainz, Dept Med 1, D-55101 Mainz, Germany.
[Gerhold-Ay, Aslihan; Victor, Anja; Binder, Harald; Blettner, Maria] Johannes Gutenberg Univ Mainz, Inst Med Biostat Epidemiol & Informat, D-55101 Mainz, Germany.
[Thorgeirsson, Snorri] NCI, Expt Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA.
RP Teufel, A (reprint author), Johannes Gutenberg Univ Mainz, Dept Med 1, Bldg 605,Langenbeckstr 1, D-55101 Mainz, Germany.
EM teufel@uni-mainz.de
RI Binder, Harald/C-7413-2009
OI Binder, Harald/0000-0002-5666-8662
NR 43
TC 13
Z9 14
U1 0
U2 1
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1476-4598
J9 MOL CANCER
JI Mol. Cancer
PD AUG 14
PY 2012
VL 11
AR 55
DI 10.1186/1476-4598-11-55
PG 11
WC Biochemistry & Molecular Biology; Oncology
SC Biochemistry & Molecular Biology; Oncology
GA 068BM
UT WOS:000313339500001
PM 22891627
ER
PT J
AU Huang, ZJ
Das, A
Qiu, YL
Tatem, AJ
AF Huang, Zhuojie
Das, Anirrudha
Qiu, Youliang
Tatem, Andrew J.
TI Web-based GIS: the vector-borne disease airline importation risk
(VBD-AIR) tool
SO INTERNATIONAL JOURNAL OF HEALTH GEOGRAPHICS
LA English
DT Article
DE Infectious disease; Air transport network; Imported disease; Web GIS;
Malaria; Dengue; Yellow fever; Chikungunya; Mosquito
ID DOMINANT ANOPHELES VECTORS; INFECTIOUS-DISEASE; DISTRIBUTION MAPS;
BIONOMIC PRECIS; HUMAN MALARIA; TRANSPORTATION NETWORK;
AEDES-ALBOPICTUS; YELLOW-FEVER; SPREAD; WORLDWIDE
AB Background: Over the past century, the size and complexity of the air travel network has increased dramatically. Nowadays, there are 29.6 million scheduled flights per year and around 2.7 billion passengers are transported annually. The rapid expansion of the network increasingly connects regions of endemic vector-borne disease with the rest of the world, resulting in challenges to health systems worldwide in terms of vector-borne pathogen importation and disease vector invasion events. Here we describe the development of a user-friendly Web-based GIS tool: the Vector-Borne Disease Airline Importation Risk Tool (VBD-AIR), to help better define the roles of airports and airlines in the transmission and spread of vector-borne diseases.
Methods: Spatial datasets on modeled global disease and vector distributions, as well as climatic and air network traffic data were assembled. These were combined to derive relative risk metrics via air travel for imported infections, imported vectors and onward transmission, and incorporated into a three-tier server architecture in a Model-View-Controller framework with distributed GIS components. A user-friendly web-portal was built that enables dynamic querying of the spatial databases to provide relevant information.
Results: The VBD-AIR tool constructed enables the user to explore the interrelationships among modeled global distributions of vector-borne infectious diseases (malaria. dengue, yellow fever and chikungunya) and international air service routes to quantify seasonally changing risks of vector and vector-borne disease importation and spread by air travel, forming an evidence base to help plan mitigation strategies. The VBD-AIR tool is available at www.vbd-air.com.
Conclusions: VBD-AIR supports a data flow that generates analytical results from disparate but complementary datasets into an organized cartographical presentation on a web map for the assessment of vector-borne disease movements on the air travel network. The framework built provides a flexible and robust informatics infrastructure by separating the modules of functionality through an ontological model for vector-borne disease. The VBD-AIR tool is designed as an evidence base for visualizing the risks of vector-borne disease by air travel for a wide range of users, including planners and decisions makers based in state and local government, and in particular, those at international and domestic airports tasked with planning for health risks and allocating limited resources.
C1 [Huang, Zhuojie; Qiu, Youliang; Tatem, Andrew J.] Univ Florida, Dept Geog, Gainesville, FL 32611 USA.
[Huang, Zhuojie; Das, Anirrudha; Qiu, Youliang; Tatem, Andrew J.] Univ Florida, Emerging Pathogen Inst, Gainesville, FL 32611 USA.
[Tatem, Andrew J.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
RP Huang, ZJ (reprint author), Univ Florida, Dept Geog, Gainesville, FL 32611 USA.
EM seenhzj@gmail.com
FU NCATS NIH HHS [UL1 TR000064]
NR 51
TC 19
Z9 19
U1 2
U2 46
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1476-072X
J9 INT J HEALTH GEOGR
JI Int. J. Health Geogr.
PD AUG 14
PY 2012
VL 11
AR 33
DI 10.1186/1476-072X-11-33
PG 14
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 044NL
UT WOS:000311626600001
PM 22892045
ER
PT J
AU Yutin, N
Koonin, EV
AF Yutin, Natalya
Koonin, Eugene V.
TI Hidden evolutionary complexity of Nucleo-Cytoplasmic Large DNA viruses
of eukaryotes
SO VIROLOGY JOURNAL
LA English
DT Article
ID HORIZONTAL GENE-TRANSFER; GIANT VIRUSES; MELTING-POT; GENOME; MIMIVIRUS;
SEQUENCE; AMEBAS; ORIGIN; MICROORGANISMS; PHYLOGENIES
AB Background: The Nucleo-Cytoplasmic Large DNA Viruses (NCLDV) constitute an apparently monophyletic group that consists of at least 6 families of viruses infecting a broad variety of eukaryotic hosts. A comprehensive genome comparison and maximum-likelihood reconstruction of the NCLDV evolution revealed a set of approximately 50 conserved, core genes that could be mapped to the genome of the common ancestor of this class of eukaryotic viruses.
Results: We performed a detailed phylogenetic analysis of these core NCLDV genes and applied the constrained tree approach to show that the majority of the core genes are unlikely to be monophyletic. Several of the core genes have been independently acquired from different sources by different NCLDV lineages whereas for the majority of these genes displacement by homologs from cellular organisms in one or more groups of the NCLDV was demonstrated.
Conclusions: A detailed study of the evolution of the genomic core of the NCLDV reveals substantial complexity and diversity of evolutionary scenarios that was largely unsuspected previously. The phylogenetic coherence between the core genes is sufficient to validate the hypothesis on the evolution of all NCLDV from a common ancestral virus although the set of ancestral genes might be smaller than previously inferred from patterns of gene presence-absence.
C1 [Yutin, Natalya; 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 DHHS intramural program (NIH, national Library of Medicine)
FX The authors' research is supported by the DHHS intramural program (NIH,
national Library of Medicine).
NR 40
TC 54
Z9 55
U1 0
U2 20
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1743-422X
J9 VIROL J
JI Virol. J.
PD AUG 14
PY 2012
VL 9
AR 161
DI 10.1186/1743-422X-9-161
PG 18
WC Virology
SC Virology
GA 037RE
UT WOS:000311123400001
PM 22891861
ER
PT J
AU Berezhkovskii, AM
AF Berezhkovskii, Alexander M.
TI Note: Aris-Taylor dispersion from single-particle point of view
SO JOURNAL OF CHEMICAL PHYSICS
LA English
DT Letter
C1 NIH, Math & Stat Comp Lab, Div Computat Biosci, Ctr Informat Technol, Bethesda, MD 20892 USA.
RP Berezhkovskii, AM (reprint author), NIH, Math & Stat Comp Lab, Div Computat Biosci, Ctr Informat Technol, Bldg 10, Bethesda, MD 20892 USA.
FU Intramural NIH HHS
NR 3
TC 3
Z9 3
U1 0
U2 3
PU AMER INST PHYSICS
PI MELVILLE
PA CIRCULATION & FULFILLMENT DIV, 2 HUNTINGTON QUADRANGLE, STE 1 N O 1,
MELVILLE, NY 11747-4501 USA
SN 0021-9606
J9 J CHEM PHYS
JI J. Chem. Phys.
PD AUG 14
PY 2012
VL 137
IS 6
AR 066101
DI 10.1063/1.4746027
PG 2
WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical
SC Chemistry; Physics
GA 995XN
UT WOS:000308048700067
PM 22897315
ER
PT J
AU Dorjgochoo, T
Shu, XO
Xiang, YB
Yang, G
Cai, QY
Li, HL
Ji, BT
Cai, H
Gao, YT
Zheng, W
AF Dorjgochoo, Tsogzolmaa
Shu, Xiao Ou
Xiang, Yong-Bing
Yang, Gong
Cai, Qiuyin
Li, Honglan
Ji, Bu-Tian
Cai, Hui
Gao, Yu-Tang
Zheng, Wei
TI Circulating 25-hydroxyvitamin D levels in relation to blood pressure
parameters and hypertension in the Shanghai Women's and Men's Health
Studies
SO BRITISH JOURNAL OF NUTRITION
LA English
DT Article
DE Blood pressure parameters; Hypertension; 25-Hydroxyvitamin D; Sex
differences; China
ID NUTRITION EXAMINATION SURVEY; CARDIOVASCULAR RISK-FACTORS;
PARATHYROID-HORMONE LEVELS; RENIN-ANGIOTENSIN SYSTEM; VITAMIN-D
ALPHACALCIDOL; 3RD NATIONAL-HEALTH; LONG-TERM TREATMENT; DOUBLE-BLIND;
INSULIN SENSITIVITY; METABOLIC SYNDROME
AB Little is known about the association of circulating 25-hydroxyvitamin D (25(OH) D) and blood pressure (BP) parameters, including systolic and diastolic BP, pulse pressure (PP), mean arterial pressure (MAP) and hypertension in non-Western populations that have not yet been exposed to foods fortified with vitamins and seldom use vitamin D supplements. A cross-sectional analysis of plasma 25(OH) D levels in association with BP measures was performed for 1460 participants (1055 women and 405 men, aged 40-74 years) of two large cohort studies in Shanghai. Multivariable linear and logistic regressions were conducted. Overall, the prevalence of vitamin D deficiency was 55.8% using National Health and Nutrition Examination Survey, USA criteria and 29.9% using WHO criteria. The median plasma 25(OH)D level in the population was 38.0 nmol/l for men and 33.6 nmol/l for women (P<0.01) among participants who were not on antihypertensive drugs. Among men, BP parameters (systolic BP, diastolic BP and MAP) were significantly and inversely associated with higher quintiles of 25(OH)D compared with the lowest quintile (P-trend < 0.05 for all). Vitamin D non-deficient status (WHO criteria) was inversely associated with hypertension (ORadjusted = 0.29; 95% CI 0.10, 0.82). An inverse association was also found between hypertension and the highest quintile of 25(OH)D (ORadjusted = 0.16; 95% CI 0.04, 0.65 for >= 50.6 nmol/l; Ptrend 0.02). Among women, no significant associations were found for BP parameters and hypertension. The present study shows that vitamin D deficiency is common among adults in urban China. Circulating 25(OH)D levels were inversely related to the levels of individual BP parameters and hypertension among middle-aged and elderly men but not among women. More research is needed to investigate the potential sex differential associations.
C1 [Dorjgochoo, Tsogzolmaa; Shu, Xiao Ou; Yang, Gong; Cai, Qiuyin; Cai, Hui; Zheng, Wei] Vanderbilt Univ, Sch Med, IMPH, Div Epidemiol,Dept Med, Nashville, TN 37203 USA.
[Dorjgochoo, Tsogzolmaa; Shu, Xiao Ou; Yang, Gong; Cai, Qiuyin; Cai, Hui; Zheng, Wei] Vanderbilt Univ, Sch Med, IMPH, Vanderbilt Epidemiol Ctr, Nashville, TN 37203 USA.
[Xiang, Yong-Bing; Li, Honglan; Gao, Yu-Tang] Shanghai Canc Inst, Dept Epidemiol, Shanghai 200032, Peoples R China.
[Ji, Bu-Tian] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
RP Shu, XO (reprint author), Vanderbilt Univ, Sch Med, IMPH, Div Epidemiol,Dept Med, 2525 W End Ave,Suite 600, Nashville, TN 37203 USA.
EM xiao-ou.shu@vanderbilt.edu
FU National Cancer Institute at the National Institutes of Health, USA [R37
CA070867, R01 CA082729, R01 HL079123]
FX The contributions of the authors were as follows: T. D. analysed the
data and drafted the manuscript. X. O. S. and W. Z. designed and
directed the study, obtained funding for the parent studies and provided
critical review of the manuscript. Y.-B. X., G. Y., H. L. and Y.-T. G.
directed and supervised the field operations of the parent studies, data
cleaning and reviewed the manuscript. B.-T. J., G. Y. and Q. C.
contributed to critical review of the paper. H. C. contributed to the
statistical analysis and reviewed the paper. The authors thank the
Shanghai residents who participated in the studies and the research
staff of the Shanghai Women's Health Study (SWHS) and the Shanghai Men's
Health Study (SMHS) for their dedication and contributions to the
present study. The authors also thank Bethanie Rammer and Jacqueline
Stern for their editorial assistance. This work was supported by the
National Cancer Institute at the National Institutes of Health, USA (R37
CA070867, R01 CA082729, R01 HL079123). The authors declare that they
have no conflicts of interest.
NR 47
TC 15
Z9 17
U1 0
U2 10
PU CAMBRIDGE UNIV PRESS
PI CAMBRIDGE
PA EDINBURGH BLDG, SHAFTESBURY RD, CB2 8RU CAMBRIDGE, ENGLAND
SN 0007-1145
J9 BRIT J NUTR
JI Br. J. Nutr.
PD AUG 14
PY 2012
VL 108
IS 3
BP 449
EP 458
DI 10.1017/S0007114511005745
PG 10
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 999JC
UT WOS:000308304700011
PM 22365135
ER
PT J
AU Murphy, TP
Cerezo, J
Cutlip, DE
Reynolds, MR
Regensteiner, JG
Mohler, ER
Cohen, DJ
Massaro, JM
Lewis, BA
Oldenburg, NC
Steffes, MW
Hirsch, AT
Thum, CC
Goldberg, S
Jaff, MR
Comerota, AJ
Ehrman, J
Treat-Jacobson, D
Bronas, U
Walsh, ME
Badenhop, DT
Collins, T
AF Murphy, Timothy P.
Cerezo, Joselyn
Cutlip, Donald E.
Reynolds, Matthew R.
Regensteiner, Judith G.
Mohler, Emile R.
Cohen, David J.
Massaro, Joseph M.
Lewis, Beth A.
Oldenburg, Niki C.
Steffes, Michael W.
Hirsch, Alan T.
Thum, Claudia C.
Goldberg, Suzanne
Jaff, Michael R.
Comerota, Anthony J.
Ehrman, Jonathan
Treat-Jacobson, Diane
Bronas, Ulf
Walsh, M. Eileen
Badenhop, Dalynn T.
Collins, Tracie
TI Response to Letters Regarding Article, "Supervised Exercise Versus
Primary Stenting for Claudication Resulting From Aortoiliac Peripheral
Artery Disease: Six-Month Outcomes From the Claudication: Exercise
Versus Endoluminal Revascularization (CLEVER) Study"
SO CIRCULATION
LA English
DT Letter
C1 [Murphy, Timothy P.; Cerezo, Joselyn] Rhode Isl Hosp, Providence, RI 02903 USA.
[Cutlip, Donald E.; Reynolds, Matthew R.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
[Regensteiner, Judith G.] Univ Colorado, Sch Med, Aurora, CO USA.
[Mohler, Emile R.] Univ Penn, Philadelphia, PA 19104 USA.
[Cohen, David J.] Univ Missouri, Kansas City, MO 64110 USA.
[Massaro, Joseph M.] Boston Univ, Boston, MA 02215 USA.
[Lewis, Beth A.] Univ Minnesota, Sch Kinesiol, Minneapolis, MN USA.
[Oldenburg, Niki C.; Steffes, Michael W.; Hirsch, Alan T.] Univ Minnesota, Sch Med, Minneapolis, MN 55455 USA.
[Thum, Claudia C.] Harvard Clin Res Inst, Boston, MA USA.
[Goldberg, Suzanne] NHLBI, Bethesda, MD 20892 USA.
[Jaff, Michael R.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Comerota, Anthony J.] Jobst Vasc Ctr, Toledo, OH USA.
[Ehrman, Jonathan] Henry Ford Hosp, Detroit, MI 48202 USA.
[Treat-Jacobson, Diane; Bronas, Ulf] Univ Minnesota, Sch Nursing, Minneapolis, MN 55455 USA.
[Walsh, M. Eileen] Univ Toledo, Coll Nursing, Toledo, OH 43606 USA.
[Collins, Tracie] Univ Kansas, Sch Med, Witchita Dept Prevent Med & Publ Hlth, Wichita, KS USA.
RP Murphy, TP (reprint author), Rhode Isl Hosp, Providence, RI 02903 USA.
NR 1
TC 0
Z9 0
U1 0
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD AUG 14
PY 2012
VL 126
IS 7
BP E102
EP E103
DI 10.1161/CIRCULATIONAHA.112.113704
PG 2
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 993TQ
UT WOS:000307882900006
ER
PT J
AU Roberts, KG
Morin, RD
Zhang, JH
Hirst, M
Zhao, YJ
Su, XP
Chen, SC
Payne-Turner, D
Churchman, ML
Harvey, RC
Chen, X
Kasap, C
Yan, CH
Becksfort, J
Finney, RP
Teachey, DT
Maude, SL
Tse, K
Moore, R
Jones, S
Mungall, K
Birol, I
Edmonson, MN
Hu, Y
Buetow, KE
Chen, IM
Carroll, WL
Wei, L
Ma, J
Kleppe, M
Levine, RL
Garcia-Manero, G
Larsen, E
Shah, NP
Devidas, M
Reaman, G
Smith, M
Paugh, SW
Evans, WE
Grupp, SA
Jeha, S
Pui, CH
Gerhard, DS
Downing, JR
Willman, CL
Loh, M
Hunger, SP
Marra, MA
Mullighan, CG
AF Roberts, Kathryn G.
Morin, Ryan D.
Zhang, Jinghui
Hirst, Martin
Zhao, Yongjun
Su, Xiaoping
Chen, Shann-Ching
Payne-Turner, Debbie
Churchman, Michelle L.
Harvey, Richard C.
Chen, Xiang
Kasap, Corynn
Yan, Chunhua
Becksfort, Jared
Finney, Richard P.
Teachey, David T.
Maude, Shannon L.
Tse, Kane
Moore, Richard
Jones, Steven
Mungall, Karen
Birol, Inanc
Edmonson, Michael N.
Hu, Ying
Buetow, Kenneth E.
Chen, I-Ming
Carroll, William L.
Wei, Lei
Ma, Jing
Kleppe, Maria
Levine, Ross L.
Garcia-Manero, Guillermo
Larsen, Eric
Shah, Neil P.
Devidas, Meenakshi
Reaman, Gregory
Smith, Malcolm
Paugh, Steven W.
Evans, William E.
Grupp, Stephan A.
Jeha, Sima
Pui, Ching-Hon
Gerhard, Daniela S.
Downing, James R.
Willman, Cheryl L.
Loh, Mignon
Hunger, Stephen P.
Marra, Marco A.
Mullighan, Charles G.
TI Genetic Alterations Activating Kinase and Cytokine Receptor Signaling in
High-Risk Acute Lymphoblastic Leukemia
SO CANCER CELL
LA English
DT Article
ID ACUTE MYELOID-LEUKEMIA; CHRONIC MYELOMONOCYTIC LEUKEMIA; GROWTH-FACTOR
RECEPTOR; OF-FUNCTION MUTATIONS; BCR-JAK2 FUSION GENE;
MYELOPROLIFERATIVE NEOPLASMS; FLT3 MUTATIONS; NUCLEAR-PORE;
B-PROGENITOR; CHILDHOOD
AB Genomic profiling has identified a subtype of high-risk B-progenitor acute lymphoblastic leukemia (B-ALL) with alteration of IKZF1, a gene expression profile similar to BCR-ABL1-positive ALL and poor outcome (Ph-like ALL). The genetic alterations that activate kinase signaling in Ph-like ALL are poorly understood. We performed transcriptome and whole genome sequencing on 15 cases of Ph-like ALL and identified rearrangements involving ABL1, JAK2, PDGFRB, CRLF2, and EPOR, activating mutations of IL7R and FLT3, and deletion of SH2B3, which encodes the JAK2-negative regulator LNK. Importantly, several of these alterations induce transformation that is attenuated with tyrosine kinase inhibitors, suggesting the treatment outcome of these patients may be improved with targeted therapy.
C1 [Hunger, Stephen P.] Univ Colorado, Sch Med, Aurora, CO 80045 USA.
[Roberts, Kathryn G.; Su, Xiaoping; Chen, Shann-Ching; Payne-Turner, Debbie; Churchman, Michelle L.; Wei, Lei; Ma, Jing; Downing, James R.; Mullighan, Charles G.] St Jude Childrens Res Hosp, Dept Pathol, Memphis, TN 38105 USA.
[Zhang, Jinghui; Chen, Xiang] St Jude Childrens Res Hosp, Dept Computat Biol & Bioinformat, Memphis, TN 38105 USA.
[Becksfort, Jared] St Jude Childrens Res Hosp, Dept Informat Sci, Memphis, TN 38105 USA.
[Jeha, Sima; Pui, Ching-Hon] St Jude Childrens Res Hosp, Dept Oncol, Memphis, TN 38105 USA.
[Paugh, Steven W.; Evans, William E.] St Jude Childrens Res Hosp, Dept Pharmaceut Sci, Memphis, TN 38105 USA.
[Morin, Ryan D.; Hirst, Martin; Zhao, Yongjun; Tse, Kane; Moore, Richard; Jones, Steven; Mungall, Karen; Birol, Inanc; Marra, Marco A.] BC Canc Agcy, Genome Sci Ctr, Vancouver, BC V5Z 1L3, Canada.
[Harvey, Richard C.; Chen, I-Ming; Willman, Cheryl L.] Univ New Mexico, Canc Res & Treatment Ctr, Albuquerque, NM 87131 USA.
[Kasap, Corynn; Shah, Neil P.] Univ Calif San Francisco, Sch Med, San Francisco, CA 94143 USA.
[Loh, Mignon] Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94143 USA.
[Yan, Chunhua; Finney, Richard P.] NCI, Ctr Bioinformat & Informat Technol, NIH, Bethesda, MD 20892 USA.
[Edmonson, Michael N.; Hu, Ying; Buetow, Kenneth E.] NCI, Lab Populat Genet, NIH, Bethesda, MD 20892 USA.
[Smith, Malcolm] NCI, Canc Therapy Evaluat Program, NIH, Bethesda, MD 20892 USA.
[Gerhard, Daniela S.] NCI, Off Canc Genom, NIH, Bethesda, MD 20892 USA.
[Teachey, David T.; Maude, Shannon L.; Grupp, Stephan A.] Childrens Hosp Philadelphia, Div Oncol, Philadelphia, PA 19104 USA.
[Carroll, William L.] NYU, Inst Canc, New York, NY 10016 USA.
[Kleppe, Maria; Levine, Ross L.] Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, New York, NY 10065 USA.
[Garcia-Manero, Guillermo] Univ Texas Houston, MD Anderson Canc Ctr, Dept Leukemia, Houston, TX 77030 USA.
[Larsen, Eric] Maine Childrens Canc Program, Scarborough, ME 04074 USA.
[Devidas, Meenakshi] Univ Florida, Gainesville, FL 32601 USA.
[Reaman, Gregory] Childrens Natl Med Ctr, Washington, DC 20010 USA.
[Marra, Marco A.] Univ British Columbia, Dept Med Genet, Vancouver, BC VSZ 1L3, Canada.
[Hunger, Stephen P.] Childrens Hosp Colorado, Aurora, CO 80045 USA.
RP Hunger, SP (reprint author), Univ Colorado, Sch Med, Aurora, CO 80045 USA.
EM stephen.hunger@childrenscolorado.org; mmarra@bcgsc.ca;
charles.mullighan@stjude.org
RI Paugh, Steven/A-7739-2008; Kleppe, Maria/C-6341-2014; Tang,
Macy/B-9798-2014; Hirst, Martin/B-7684-2016; Jones, Steven/C-3621-2009;
Marra, Marco/B-5987-2008; Birol, Inanc/G-5440-2011;
OI Paugh, Steven/0000-0001-5697-9228; Kleppe, Maria/0000-0002-4372-6704;
Birol, Inanc/0000-0003-0950-7839; Harvey, Richard/0000-0002-4904-9767;
Mullighan, Charles/0000-0002-1871-1850
FU NCI; NIH, Therapeutically Applicable Research to Generate Effective
Treatments initiative [N01-C0-12400]; Children's Oncology Group Chair's
award [CA098543]; National Cancer Institute Strategic Partnering to
Evaluate Cancer Signatures Program [CA114762]; NIH Cancer Center Core
Grant [CA21765]; St. Jude Children's Research Hospital - Washington
University Pediatric Cancer Genome Project; Stand Up To Cancer
Innovative Research Grant; American Lebanese Syrian Associated Charities
of St. Jude Children's Research Hospital; National Health and Medical
Research Council (Australia); Haematology Society of Australia; New
Zealand Novartis New Investigator Scholarship; MSFHR; [U10 CA98543];
[U10 CA98413]; [U24 CA114766]
FX We thank M. Tomasson and J. Cools for providing the
MSCV-ETV6-PDGFRB-IRES-GFP and MSCV-NUP214-ABL1-IRES-GFP constructs,
respectively; D. Pei and C. Cheng for statistical analyses of cell line
proliferation data; Garry Nolan for providing the Phoenix cell line
(http://www.stanford.edu/group/nolan/retroviral_systems/phx.html);
Beckman Coulter Genomics for Sanger Sequencing; and the Flow Cytometry
Core Facility, Tissue Resources Core Facility, and Clinical Application
of Core Technology (Affymetrix) Laboratory of the Hartwell Center for
Bioinformatics and Biotechnology of St. Jude Children's Research
Hospital. The correlative biology studies described in this manuscript
were funded by grants from the National Institutes of Health (NIH) and
philanthropic funds of the Children's Oncology Group and not a
commercial entity. The sequencing was part-funded with Federal funds
from the NCI and NIH under Contract No. N01-C0-12400 as part of the
Therapeutically Applicable Research to Generate Effective Treatments
initiative. This work was supported by funds provided as a supplement to
the Children's Oncology Group Chair's award (CA098543, G.R.); grants to
the COG, including U10 CA98543 (COG Chair's grant), U10 CA98413 (COG
Statistical Center), and U24 CA114766 (COG Specimen Banking); a National
Cancer Institute Strategic Partnering to Evaluate Cancer Signatures
Program award CA114762 (W.L.C., I-M.C., R.C.H., and C.L.W.); NIH Cancer
Center Core Grant CA21765 (J.R.D., C.G.M., W.E.E., C.-H.P., and S.J.);
St. Jude Children's Research Hospital - Washington University Pediatric
Cancer Genome Project; a Stand Up To Cancer Innovative Research Grant
(C.G.M.); and the American Lebanese Syrian Associated Charities of St.
Jude Children's Research Hospital. K.G.R. is supported by a National
Health and Medical Research Council (Australia) Overseas Training
Fellowship and a Haematology Society of Australia and New Zealand
Novartis New Investigator Scholarship. R.D.M. is a Vanier Scholar (CIHR)
and holds a MSFHR senior graduate studentship. M.A.M. is a UBC Canada
Research Chair in Genome Science and a Michael Smith Senior Research
Scholar. S.P.H. is the Ergen Family Chair in Pediatric Cancer. C.G.M. is
a Pew Scholar in the Biomedical Sciences and a St. Baldrick's Scholar.
S.P.H. is a member of the Bristol Myers Squibb pediatric dasatinib
advisory board.
NR 62
TC 225
Z9 231
U1 5
U2 31
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1535-6108
J9 CANCER CELL
JI Cancer Cell
PD AUG 14
PY 2012
VL 22
IS 2
BP 153
EP 166
DI 10.1016/j.ccr.2012.06.005
PG 14
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA 991FD
UT WOS:000307686000005
PM 22897847
ER
PT J
AU Sanda, T
Lawton, LN
Barrasa, MI
Fan, ZP
Kohlhammer, H
Gutierrez, A
Ma, WX
Tatarek, J
Ahn, Y
Kelliher, MA
Jamieson, CHM
Staudt, LM
Young, RA
Look, AT
AF Sanda, Takaomi
Lawton, Lee N.
Barrasa, M. Inmaculada
Fan, Zi Peng
Kohlhammer, Holger
Gutierrez, Alejandro
Ma, Wenxue
Tatarek, Jessica
Ahn, Yebin
Kelliher, Michelle A.
Jamieson, Catriona H. M.
Staudt, Louis M.
Young, Richard A.
Look, A. Thomas
TI Core Transcriptional Regulatory Circuit Controlled by the TAL1 Complex
in Human T Cell Acute Lymphoblastic Leukemia
SO CANCER CELL
LA English
DT Article
ID GENOME-WIDE ANALYSIS; GENE-EXPRESSION; TARGET GENE; PROTEINS; BINDING;
DIFFERENTIATION; ALPHA; E2A; SCL; ONCOGENE
AB The oncogenic transcription factor TAL1/SCL is aberrantly expressed in over 40% of cases of human T cell acute lymphoblastic leukemia (T-ALL), emphasizing its importance in the molecular pathogenesis of T-ALL. Here we identify the core transcriptional regulatory circuit controlled by TAL1 and its regulatory partners HEB, E2A, LMO1/2, GATA3, and RUNX1. We show that TAL1 forms a positive interconnected autoregulatory loop with GATA3 and RUNX1 and that the TAL1 complex directly activates the MYB oncogene, forming a positive feed-forward regulatory loop that reinforces and stabilizes the TAL1-regulated oncogenic program. One of the critical downstream targets in this circuitry is the TRIB2 gene, which is oppositely regulated by TAL1 and E2A/HEB and is essential for the survival of T-ALL cells.
C1 [Sanda, Takaomi; Gutierrez, Alejandro; Ahn, Yebin; Look, A. Thomas] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02215 USA.
[Lawton, Lee N.; Barrasa, M. Inmaculada; Fan, Zi Peng; Young, Richard A.] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA.
[Fan, Zi Peng] MIT, Computat & Syst Biol Program, Cambridge, MA 02142 USA.
[Young, Richard A.] MIT, Dept Biol, Cambridge, MA 02142 USA.
[Kohlhammer, Holger; Staudt, Louis M.] NCI, Metab Branch, Bethesda, MD 20892 USA.
[Gutierrez, Alejandro; Look, A. Thomas] Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA.
[Ma, Wenxue; Kelliher, Michelle A.; Jamieson, Catriona H. M.] Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA.
[Ma, Wenxue; Kelliher, Michelle A.; Jamieson, Catriona H. M.] Univ Calif San Diego, Moores Canc Ctr, La Jolla, CA 92093 USA.
[Tatarek, Jessica] Univ Massachusetts, Sch Med, Dept Canc Biol, Worcester, MA 01605 USA.
RP Look, AT (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02215 USA.
EM thomas_look@dfci.harvard.edu
RI Young, Richard/F-6495-2012;
OI Young, Richard/0000-0001-8855-8647; Gutierrez,
Alejandro/0000-0002-0249-9007
FU National Cancer Institute [5P01CA109901, 5P01CA68484, 1K99CA157951];
National Institutes of Health, National Cancer Institute, Center for
Cancer Research; William Lawrence and Blanche Hughes Foundation;
Children's Leukemia Research Association; Japan Society for the
Promotion of Science; California Institute for Regenerative Medicine
Leukemia Team
FX We thank the members of the Look and Young laboratories for discussions
and critical review and Jennifer O'Neil for initial experimentation and
TAL1 plasmids. We are grateful to Garrett Frampton and Dave Orlando for
the development of ChIP-seq analysis tools and continued support with
the analysis. We are also grateful to the Whitehead Genome Technology
Core (V. Dhanapal, J.-A. Kwon, J. Love, S. Gupta, and T. Volkert) for
assistance with ChIP-Seq and expression array hybridization and to
Bingbing Yuan from BaRC for developing the phenotype ontology analysis.
We acknowledge the RNAi Consortium for providing lentivirus shRNA
constructs, and we thank John R. Gilbert for editing and critical review
of the manuscript. This research was supported by grants (5P01CA109901,
5P01CA68484, and 1K99CA157951) from the National Cancer Institute and by
the Intramural Research Program of the National Institutes of Health,
National Cancer Institute, Center for Cancer Research. T.S. is supported
by grants from the William Lawrence and Blanche Hughes Foundation, the
Children's Leukemia Research Association, and the Japan Society for the
Promotion of Science. W.M. and C.J. are supported by the California
Institute for Regenerative Medicine Leukemia Team grant.
NR 61
TC 66
Z9 67
U1 1
U2 5
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1535-6108
J9 CANCER CELL
JI Cancer Cell
PD AUG 14
PY 2012
VL 22
IS 2
BP 209
EP 221
DI 10.1016/j.ccr.2012.06.007
PG 13
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA 991FD
UT WOS:000307686000009
PM 22897851
ER
PT J
AU Cecchi, F
Pajalunga, D
Fowler, CA
Uren, A
Rabe, DC
Peruzzi, B
MacDonald, NJ
Blackman, DK
Stahl, SJ
Byrd, RA
Bottaro, DP
AF Cecchi, Fabiola
Pajalunga, Deborah
Fowler, C. Andrew
Ueren, Aykut
Rabe, Daniel C.
Peruzzi, Benedetta
MacDonald, Nicholas J.
Blackman, Davida K.
Stahl, Stephen J.
Byrd, R. Andrew
Bottaro, Donald P.
TI Targeted Disruption of Heparan Sulfate Interaction with Hepatocyte and
Vascular Endothelial Growth Factors Blocks Normal and Oncogenic
Signaling
SO CANCER CELL
LA English
DT Article
ID FACTOR/SCATTER FACTOR; CRYSTAL-STRUCTURE; C-MET; FACTOR ISOFORMS; NK1
FRAGMENT; FUNCTIONAL-CHARACTERIZATION; RECEPTOR ACTIVATION; PROVIDE
INSIGHTS; STRUCTURAL BASIS; DOMAIN RECEPTOR
AB Hepatocyte growth factor (HGF) and vascular endothelial cell growth factor (VEGF) regulate normal development and homeostasis and drive disease progression in many forms of cancer. Both proteins signal by binding to receptor tyrosine kinases and heparan sulfate (HS) proteoglycans on target cell surfaces. Basic residues comprising the primary HS binding sites on HGF and VEGF provide similar surface charge distributions without underlying structural similarity. Combining three acidic amino acid substitutions in these sites in the HGF isoform NK1 or the VEGF isoform VEGF165 transformed each into potent, selective competitive antagonists of their respective normal and oncogenic signaling pathways. Our findings illustrate the importance of HS in growth factor driven cancer progression and reveal an efficient strategy for therapeutic antagonist development.
C1 [Cecchi, Fabiola; Rabe, Daniel C.; Peruzzi, Benedetta; Bottaro, Donald P.] NCI, Urol Oncol Branch, Bethesda, MD 20892 USA.
[Pajalunga, Deborah; Fowler, C. Andrew; Byrd, R. Andrew] Frederick Natl Lab Canc Res, Macromol NMR Sect, Struct Biophys Lab, Frederick, MD 21702 USA.
[Pajalunga, Deborah; MacDonald, Nicholas J.; Blackman, Davida K.] EntreMed Inc, Rockville, MD 20850 USA.
[Ueren, Aykut] Georgetown Univ, Med Ctr, Lombardi Comprehens Canc Ctr, Washington, DC 20057 USA.
[Stahl, Stephen J.] NIAMSD, Prot Express Lab, NIH, Bethesda, MD 20892 USA.
RP Bottaro, DP (reprint author), NCI, Urol Oncol Branch, Bethesda, MD 20892 USA.
EM dbottaro@helix.nih.gov
RI Bottaro, Donald/F-8550-2010; Byrd, R. Andrew/F-8042-2015;
OI Fowler, Andrew/0000-0001-5646-5307; Bottaro, Donald/0000-0002-5057-5334;
Byrd, R. Andrew/0000-0003-3625-4232; Cecchi, Franco/0000-0002-2035-5621
FU 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. We thank the
late Dr. Ralph Schwall for recombinant Met-Ig fusion protein; Dr.
Jeffrey Esko for CHO 745 cells; Drs. Dominic Esposito, Troy Taylor, and
William Gillette for plasmid and protein production and purification;
and Drs. Miriam Anver, Lawrence Sternberg, and Roberta Smith for
pathology, immunohistochemistry analysis, and clinical chemistry
analyses.
NR 50
TC 14
Z9 14
U1 2
U2 9
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1535-6108
J9 CANCER CELL
JI Cancer Cell
PD AUG 14
PY 2012
VL 22
IS 2
BP 250
EP 262
DI 10.1016/j.ccr.2012.06.029
PG 13
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA 991FD
UT WOS:000307686000012
PM 22897854
ER
PT J
AU Endo, Y
Ishiwata-Endo, H
Yamada, KM
AF Endo, Yukinori
Ishiwata-Endo, Hiroko
Yamada, Kenneth M.
TI Extracellular Matrix Protein Anosmin Promotes Neural Crest Formation and
Regulates FGF, BMP, and WNT Activities
SO DEVELOPMENTAL CELL
LA English
DT Article
ID LINKED KALLMANN-SYNDROME; CELL FATE SPECIFICATION; TRANSCRIPTION FACTOR;
PARAXIAL MESODERM; INDUCTION; GASTRULATION; CHICK; GENE;
DIFFERENTIATION; REQUIRES
AB Neural crest cells are a transient stem cell-like population appearing during vertebrate embryonic development. Generation of the cranial neural crest is known to require a balanced combination of FGF and BMP levels. However, it is poorly understood how the functions of such growth factors are controlled in the extracellular space. Anosmin is an extracellular matrix protein implicated in FGF signaling and mutated in Kallmann syndrome. Here, we demonstrate that anosmin is synthesized locally in the cranial neural crest of chicken embryos and is essential for cranial neural crest formation. Anosmin upregulates FGF8 and BMP5 gene expression; it also enhances FGF8 activity while inhibiting BMP5 and WNT3a signaling. Taken together, our data establish that the matrix protein anosmin is required for cranial neural crest formation, with functional modulation of FGF, BMP, and WNT.
C1 [Endo, Yukinori; Ishiwata-Endo, Hiroko; Yamada, Kenneth M.] Natl Inst Dent & Craniofacial Res, Lab Cell & Dev Biol, NIH, Bethesda, MD 20892 USA.
RP Endo, Y (reprint author), Natl Inst Dent & Craniofacial Res, Lab Cell & Dev Biol, NIH, Bethesda, MD 20892 USA.
EM yukinorishiko@yahoo.co.jp; kenneth.yamada@nih.gov
OI Yamada, Kenneth/0000-0003-1512-6805
FU National Institute of Dental and Craniofacial Research, National
Institutes of Health; Japan Society for the Promotion of Science
Research
FX We thank Dr. Woei-Jer Chuang for valuable advice on anosmin protein
purification, members of the Yamada laboratory for comments, and Shelagh
Johnson for proofreading. We especially thank Drs. Daniel Rifkin, Dwight
Towler, and Angela Nieto for kindly providing C2C12-BRA cells, 7xOCFRE,
and 3xOCFRE plasmids and chicken SNAI2 plasmid, respectively. Supported
by the Intramural Research Program of the National Institute of Dental
and Craniofacial Research, National Institutes of Health. Y.E. was
partially supported by the Japan Society for the Promotion of Science
Research.
NR 54
TC 27
Z9 27
U1 1
U2 8
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1534-5807
J9 DEV CELL
JI Dev. Cell
PD AUG 14
PY 2012
VL 23
IS 2
BP 305
EP 316
DI 10.1016/j.devcel.2012.07.006
PG 12
WC Cell Biology; Developmental Biology
SC Cell Biology; Developmental Biology
GA 991IU
UT WOS:000307695500010
PM 22898776
ER
PT J
AU Frontini, M
Kukalev, A
Leo, E
Ng, YM
Cervantes, M
Cheng, CW
Holic, R
Dormann, D
Tse, E
Pommier, Y
Yu, V
AF Frontini, Mattia
Kukalev, Alexander
Leo, Elisabetta
Yiu-Ming Ng
Cervantes, Marcella
Cheng, Chi-Wai
Holic, Roman
Dormann, Dirk
Tse, Eric
Pommier, Yves
Yu, Veronica
TI The CDK Subunit CKS2 Counteracts CKS1 to Control Cyclin A/CDK2 Activity
in Maintaining Replicative Fidelity and Neurodevelopment
SO DEVELOPMENTAL CELL
LA English
DT Article
ID DNA-DAMAGE RESPONSE; S-PHASE CHECKPOINT; CELL-CYCLE; NEURONAL
DIFFERENTIATION; INDEPENDENT FUNCTION; EARLY EMBRYOGENESIS; DEPENDENT
KINASES; PROGENITOR CELLS; MAMMALIAN-CELLS; CEREBRAL-CORTEX
AB CKS proteins are evolutionarily conserved cyclin-dependent kinase (CDK) subunits whose functions are incompletely understood. Mammals have two CKS proteins. CKS1 acts as a cofactor to the ubiquitin ligase complex SCFSKP2 to promote degradation of CDK inhibitors, such as p27. Little is known about the role of the closely related CKS2. Using a Cks2(-/-) knockout mouse model, we show that CKS2 counteracts CKS1 and stabilizes p27. Unopposed CKS1 activity in Cks2-/- cells leads to loss of p27. The resulting unrestricted cyclin A/CDK2 activity is accompanied by shortening of the cell cycle, increased replication fork velocity, and DNA damage. In vivo, Cks2(-/-) cortical progenitor cells are limited in their capacity to differentiate into mature neurons, a phenotype akin to animals lacking p27. We propose that the balance between CKS2 and CKS1 modulates p27 degradation, and with it cyclin A/CDK2 activity, to safeguard replicative fidelity and control neuronal differentiation.
C1 [Frontini, Mattia; Kukalev, Alexander; Cervantes, Marcella; Holic, Roman; Yu, Veronica] Univ London Imperial Coll Sci Technol & Med, MRC Clin Sci Ctr, Eukaryot Chromatin Dynam Grp, London W12 0NN, England.
[Dormann, Dirk] Univ London Imperial Coll Sci Technol & Med, MRC Clin Sci Ctr, Microscopy Facil, London W12 0NN, England.
[Kukalev, Alexander; Yiu-Ming Ng; Yu, Veronica] Kings Coll London, Sch Med, Guys Hosp, Dept Med & Mol Genet, London SE1 9RT, England.
[Leo, Elisabetta; Pommier, Yves] NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Yiu-Ming Ng; Cheng, Chi-Wai; Tse, Eric] Univ Hong Kong, Dept Med, Div Haematol, Hong Kong, Hong Kong, Peoples R China.
[Holic, Roman] Slovak Acad Sci, Inst Anim Biochem & Genet, Ivanka Pri Dunaji 90028, Slovakia.
RP Yu, V (reprint author), Univ London Imperial Coll Sci Technol & Med, MRC Clin Sci Ctr, Eukaryot Chromatin Dynam Grp, Hammersmith Campus,Du Cane Rd, London W12 0NN, England.
EM veronica.yu@kcl.ac.uk
OI Holic, Roman/0000-0003-1347-4785
FU Medical Research Council; Cancer Research UK; Generation Trust; Academy
of Medical Sciences; Wellcome Trust; British Heart Foundation; National
Institute for Health Research at Guy's NHS Foundation Trust; National
Institute for Health Research at St. Thomas' NHS Foundation Trust;
King's College London; Outstanding Young Researcher Award, University of
Hong Kong; National Institutes of Health Intramural Program, Center for
Cancer Research, National Cancer Institute
FX We thank V. de Paola and H. Dewchand for kind assistance and expertise
in preparation of mouse brains. The Yu laboratory is funded by the
Medical Research Council, Cancer Research UK, the Generation Trust, the
Academy of Medical Sciences, the Wellcome Trust, and the British Heart
Foundation. V.Y. is supported by a fellowship from the National
Institute for Health Research at Guy's and St. Thomas' NHS Foundation
Trust in partnership with King's College London. E.T. is a recipient of
the Outstanding Young Researcher Award 2010, University of Hong Kong.
The Pommier laboratory is funded by the National Institutes of Health
Intramural Program, Center for Cancer Research, National Cancer
Institute.
NR 50
TC 11
Z9 11
U1 1
U2 12
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1534-5807
J9 DEV CELL
JI Dev. Cell
PD AUG 14
PY 2012
VL 23
IS 2
BP 356
EP 370
DI 10.1016/j.devcel.2012.06.018
PG 15
WC Cell Biology; Developmental Biology
SC Cell Biology; Developmental Biology
GA 991IU
UT WOS:000307695500014
PM 22898779
ER
PT J
AU Hlatky, MA
Douglas, PS
Cook, NL
Wells, B
Benjamin, EJ
Dickersin, K
Goff, DC
Hirsch, AT
Hylek, EM
Peterson, ED
Roger, VL
Selby, JV
Udelson, JE
Lauer, MS
AF Hlatky, Mark A.
Douglas, Pamela S.
Cook, Nakela L.
Wells, Barbara
Benjamin, Emelia J.
Dickersin, Kay
Goff, David C.
Hirsch, Alan T.
Hylek, Elaine M.
Peterson, Eric D.
Roger, Veronique L.
Selby, Joseph V.
Udelson, James E.
Lauer, Michael S.
TI Future Directions for Cardiovascular Disease Comparative Effectiveness
Research Report of a Workshop Sponsored by the National Heart, Lung, and
Blood Institute
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Article
DE clinical trials; comparative effectiveness; research methods
ID 10-YEAR FOLLOW-UP; MYOCARDIAL-INFARCTION; ATRIAL-FIBRILLATION;
CLINICAL-TRIALS; GLUCOSE CONTROL; BYPASS SURGERY; OUTCOMES; RISK;
SURVIVAL; INTERVENTION
AB Comparative effectiveness research (CER) aims to provide decision makers with the evidence needed to evaluate the benefits and harms of alternative clinical management strategies. CER has become a national priority, with considerable new research funding allocated. Cardiovascular disease is a priority area for CER. This workshop report provides an overview of CER methods, with an emphasis on practical clinical trials and observational treatment comparisons. The report also details recommendations to the National Heart, Lung, and Blood Institute for a new framework for evidence development to foster cardiovascular CER, and specific studies to address 8 clinical issues identified by the Institute of Medicine as high priorities for cardiovascular CER. (J Am Coll Cardiol 2012; 60: 569-80) (C) 2012 by the American College of Cardiology Foundation
C1 [Hlatky, Mark A.] Stanford Univ, Sch Med, Stanford, CA 94305 USA.
[Douglas, Pamela S.; Lauer, Michael S.] Duke Univ, Med Ctr, Durham, NC USA.
[Cook, Nakela L.; Wells, Barbara; Lauer, Michael S.] NHLBI, Bethesda, MD 20892 USA.
[Benjamin, Emelia J.; Hylek, Elaine M.] Boston Univ, Sch Med, Boston, MA 02118 USA.
[Dickersin, Kay] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA.
[Goff, David C.] Wake Forest Univ Hlth Sci, Winston Salem, NC USA.
[Hirsch, Alan T.] Univ Minnesota, Sch Med, Minneapolis, MN 55455 USA.
[Roger, Veronique L.] Mayo Clin, Rochester, MN USA.
[Udelson, James E.] Tufts Univ, Sch Med, Boston, MA 02111 USA.
RP Hlatky, MA (reprint author), Stanford Univ, Sch Med, HRP Redwood Bldg,Room T150,259 Campus Dr, Stanford, CA 94305 USA.
EM hlatky@stanford.edu
RI Lauer, Michael/L-9656-2013;
OI Lauer, Michael/0000-0002-9217-8177; Benjamin, Emelia/0000-0003-4076-2336
FU NHLBI
FX From the *Stanford University School of Medicine, Stanford, California;
dagger Duke University Medical Center, Durham, North Carolina; National
Heart, Lung, and Blood Institute, Bethesda, Maryland; Boston University
School of Medicine, Boston, Massachusetts; parallel to Johns Hopkins
Bloomberg School of Public Health, Baltimore, Maryland; Wake Forest
University Health Sciences, Winston-Salem, North Carolina; #University
of Minnesota Medical School, Minneapolis, Minnesota; and the **Mayo
Clinic, Rochester, Minnesota. dagger dagger Division of Research, Kaiser
Permanente of Northern California, Oakland, California; and the Tufts
University School for Medicine, Boston, Massachusetts. Drs. Cook, Wells,
and Lauer are full-time employees of the National Heart, Lung, and Blood
Institute (NHLBI). The views expressed in this manuscript do not
necessarily represent the views of the NHLBI, National Institutes of
Health, or any other government entity. Dr. Goff is a research
consultant for and a data and safety monitoring board member for a
clinical trial of a glucose-lowering medication marketed by Merck and
Takeda. Dr. Hirsch has relationships with Pozen Medical, Merck,
AstraZeneca, Abbott Vascular, Viromed, Summit Doppler, Novartis, and
Cytokinetics. Dr. Hylek is on the scientific advisory board of Bayer,
Boehringer-Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, Johnson &
Johnson, Merck, Ortho-McNeil, and Pfizer. Dr. Selby was employed by
Kaiser Permanente and is currently the Executive Director of the Patient
Centered Outcomes Research Institute (PCORI); the opinions expressed in
this paper do not necessarily reflect those of PCORI. Dr. Udelson has
received research funding from the NHLBI. All other authors have
reported that they have no relationships relevant to the contents of
this paper to disclose. Drs. Hlatky and Douglas cochaired the workshop.
NR 40
TC 22
Z9 22
U1 0
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD AUG 14
PY 2012
VL 60
IS 7
BP 569
EP 580
DI 10.1016/j.jacc.2011.12.057
PG 12
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 988BR
UT WOS:000307463700002
PM 22796257
ER
PT J
AU Ishida, K
Nishizuka, SS
Chiba, T
Ikeda, M
Kume, K
Endo, F
Katagiri, H
Matsuo, T
Noda, H
Iwaya, T
Yamada, N
Fujiwara, H
Takahashi, M
Itabashi, T
Uesugi, N
Maesawa, C
Tamura, G
Sugai, T
Otsuka, K
Koeda, K
Wakabayashi, G
AF Ishida, Kazushige
Nishizuka, Satoshi S.
Chiba, Takehiro
Ikeda, Miyuki
Kume, Kohei
Endo, Fumitaka
Katagiri, Hirokatsu
Matsuo, Teppei
Noda, Hironobu
Iwaya, Takeshi
Yamada, Noriyuki
Fujiwara, Hisataka
Takahashi, Masanori
Itabashi, Tetsuya
Uesugi, Noriyuki
Maesawa, Chihaya
Tamura, Gen
Sugai, Tamotsu
Otsuka, Koki
Koeda, Keisuke
Wakabayashi, Go
TI Molecular Marker Identification for Relapse Prediction in 5-FU-Based
Adjuvant Chemotherapy in Gastric and Colorectal Cancers
SO PLOS ONE
LA English
DT Article
ID NF-KAPPA-B; LYSATE MICROARRAYS; GENE-EXPRESSION; JNK ACTIVATION;
COLON-CANCER; CELL-LINES; CARCINOMA; INHIBITION; ALPHA; CHEMORESISTANCE
AB To confirm the clinical significance of NF-kappa B and JNK protein expression from experimentally identified candidates for predicting prognosis for patients with 5-FU treatment, we evaluated the protein expression of surgically removed specimens. A total of 79 specimens were obtained from 30 gastric and 49 colorectal cancer patients who underwent R0 resection followed by postoperative 5-FU based adjuvant chemotherapy. Immunohistochemical examinations of NF-kappa B and JNK on tissue microarrays (TMAs) revealed that significantly shorter time-to-relapse (TTR) in both NF-kappa B(+) and JNK(-) subgroups in both gastric (NF-kappa B(+), p = 0.0002, HR11.7. 95% CI3 3.2-43.4; JNK(-), p = 0.0302, HR4.4, 95% CI 1.2-16.6) and colon (NF-kappa B(+), p = 0.0038, HR36.9, 95% CI 3.2-426.0; JNK(-), p = 0.0098, HR3.2, 95% CI 1.3-7.7) cancers. These protein expression patterns also show strong discriminately power in gastric cancer patients for overall survival rate, suggesting a potential utility as prognostic or chemosensitivity markers. Baseline expression of these proteins using gastric cancer cell lines demonstrated the reciprocal patterns between NF-kappa B and JNK, while 5-FU exposure of these cell lines only induced NF-kappa B, suggesting that NF-kappa B plays a dominant role in the response to 5-FU. Subsequent siRNA experiments confirmed that gene knockdown of NF-kappa B increased 5-FU-specific sensitivity, whereas that of JNK did not affect the chemosensitivity. These results suggest that the expression of these proteins may aid in the decisions involved with adjuvant chemotherapy for gastrointestinal tract cancers.
C1 [Ishida, Kazushige; Nishizuka, Satoshi S.; Chiba, Takehiro; Ikeda, Miyuki; Kume, Kohei; Endo, Fumitaka; Katagiri, Hirokatsu; Matsuo, Teppei; Noda, Hironobu; Iwaya, Takeshi; Fujiwara, Hisataka; Takahashi, Masanori; Itabashi, Tetsuya; Otsuka, Koki; Koeda, Keisuke; Wakabayashi, Go] Iwate Med Univ, Sch Med, Dept Surg, Morioka, Iwate 020, Japan.
[Nishizuka, Satoshi S.; Kume, Kohei; Uesugi, Noriyuki; Maesawa, Chihaya; Wakabayashi, Go] Iwate Med Univ, MIAST, Morioka, Iwate 020, Japan.
[Iwaya, Takeshi] Kyushu Univ, Med Inst Bioregulat, Dept Surg, Beppu, Oita, Japan.
[Kume, Kohei; Maesawa, Chihaya] Iwate Med Univ, Ctr Adv Med Sci, Dept Tumor Biol, Yahaba, Iwate, Japan.
[Yamada, Noriyuki; Uesugi, Noriyuki; Sugai, Tamotsu] Iwate Med Univ, Sch Med, Dept Pathol, Div Diagnost Mol Pathol, Morioka, Iwate 020, Japan.
[Tamura, Gen] Yamagata Prefectural Cent Hosp, Dept Pathol & Lab Med, Yamagata, Japan.
RP Ishida, K (reprint author), NCI, Chem Immunol Sect, Cell Biol Lab, NIH, Bethesda, MD 20892 USA.
EM snishizu@iwate-med.ac.jp
FU Keiryokai Research Foundation [101]; KAKENHI [21591676]; MIAST (Medical
Innovation by Advanced Science and Technology) project of the Ministry
of Education, Culture, Sports, Science and Technology, JAPAN
FX This work was supported by: Keiryokai Research Foundation (101) by
S.S.N.; KAKENHI (21591676); Grant-in-Aid for Scientific Research(C) by
S.S.N; and MIAST (Medical Innovation by Advanced Science and Technology)
project of the Ministry of Education, Culture, Sports, Science and
Technology, JAPAN by S.S.N, K. K, N.U., C. M., T. S., and G. W. The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 52
TC 6
Z9 7
U1 0
U2 1
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD AUG 14
PY 2012
VL 7
IS 8
AR e43236
DI 10.1371/journal.pone.0043236
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 988OQ
UT WOS:000307500800062
PM 22905237
ER
PT J
AU Gaspar, D
Veiga, AS
Sinthuvanich, C
Schneider, JP
Castanho, MARB
AF Gaspar, Diana
Veiga, Ana Salome
Sinthuvanich, Chomdao
Schneider, Joel P.
Castanho, Miguel A. R. B.
TI Anticancer Peptide SVS-1: Efficacy Precedes Membrane Neutralization
SO BIOCHEMISTRY
LA English
DT Article
ID HOST-DEFENSE PEPTIDES; ANTIMICROBIAL PEPTIDES; CANCER-TREATMENT; CHARGE
AB Anticancer peptides are polycationic amphiphiles capable of preferentially killing a wide spectrum of cancer cells relative to noncancerous cells. Their primary mode of action is an interaction with the cell membrane and subsequent activation of lytic effects; however, the exact mechanism responsible for this mode of action remains controversial. Using zeta potential analyses we demonstrate the interaction of a small anticancer peptide with membrane model systems and cancer cells. Electrostatic interactions have a pivotal role in the cell killing process, and in contrast to the antimicrobial peptides action cell death occurs without achieving full neutralization of the membrane charge.
C1 [Gaspar, Diana; Veiga, Ana Salome; Castanho, Miguel A. R. B.] Univ Lisbon, Fac Med, Inst Mol Med, P-1649028 Lisbon, Portugal.
[Sinthuvanich, Chomdao; Schneider, Joel P.] NCI, Biol Chem Lab, Frederick, MD 21702 USA.
[Sinthuvanich, Chomdao] Univ Delaware, Dept Chem & Biochem, Newark, DE 19716 USA.
RP Castanho, MARB (reprint author), Univ Lisbon, Fac Med, Inst Mol Med, Av Prof Egas Moniz, P-1649028 Lisbon, Portugal.
EM macastanho@fm.ul.pt
RI Schneider, Joel/N-2610-2014; Gaspar, Diana/M-9562-2015;
OI Gaspar, Diana/0000-0002-9602-567X; Veiga, Ana
Salome/0000-0002-9892-2243; Castanho, Miguel/0000-0001-7891-7562
FU Fundacao para a Ciencia e a Tecnologia (Ministerio da Educacao e
Ciencia, Portugal) [SFRH/BPD/73500/2010]; Marie Curie International
Outgoing Fellowship within the 7th European Community Framework
Programme [PIOF-GA-2009-235154]; Office of the Higher Education
Commission, Ministry of Education, Thailand
FX D.G. acknowledges Fundacao para a Ciencia e a Tecnologia (Ministerio da
Educacao e Ciencia, Portugal) for Fellowship SFRH/BPD/73500/2010. A.S.V.
acknowledges a Marie Curie International Outgoing Fellowship within the
7th European Community Framework Programme (PIOF-GA-2009-235154). C.S.
acknowledges the Strategic Scholarship for Frontier Research Network
(SFR) from Office of the Higher Education Commission, Ministry of
Education, Thailand.
NR 18
TC 14
Z9 14
U1 2
U2 11
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0006-2960
J9 BIOCHEMISTRY-US
JI Biochemistry
PD AUG 14
PY 2012
VL 51
IS 32
BP 6263
EP 6265
DI 10.1021/bi300836r
PG 3
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 988GY
UT WOS:000307478700001
PM 22839778
ER
PT J
AU Shukla, H
Vaitiekunas, P
Majumdar, AK
Dragan, AI
Dimitriadis, EK
Kotova, S
Crane-Robinson, C
Privalov, PL
AF Shukla, Hem
Vaitiekunas, Paulius
Majumdar, Ananya K.
Dragan, Anatoly I.
Dimitriadis, Emilios K.
Kotova, Svetlana
Crane-Robinson, Colyn
Privalov, Peter L.
TI The Linker of the Interferon Response Factor 3 Transcription Factor Is
Not Unfolded
SO BIOCHEMISTRY
LA English
DT Article
ID CRYSTAL-STRUCTURE; PROTEIN LIGATION; BETA ENHANCER; DNA-BINDING; IRF-3;
DOMAINS; NMR; PHOSPHORYLATION; TRANSACTIVATION; ACTIVATION
AB Interferon response factor 3 (IRF-3) is a transcription factor that plays an essential role in controlling the synthesis of interferon-beta (IFN-beta) and is a protein consisting of two well-defined domains, the N-terminal DNA-binding and the C-terminal dimerization domains, connected by a 75-residue linker, supposedly unfolded. However, it was not clear whether in intact IRF-3 this linker segment of the chain, which carries the nuclear export signal and includes a region of high helical propensity, remains unfolded. This has been investigated using nuclear magnetic resonance by ligating the N-15-labeled linker to the unlabeled N-terminal and C-terminal domains. It was found that, while the linker alone is indeed in a completely unfolded state, when ligated to the C-terminal domain it shows some ordering, and this ordering becomes much more pronounced when the linker is also ligated to the N-terminal domain. Thus, in intact IRF-3, the linker represents a folded structural domain; i.e., IRF-3 is a three-domain globular protein. Light scattering studies of wild-type IRF-3 showed that these three domains are tightly packed, and therefore, the dimer of IRF-3, which is formed upon phosphorylation of its C-terminal domains following virus invasion, must be a rather rigid and compact construction. One would then expect that binding of such a dimer to its tandem recognition sites PRDIII and PRDI, which are located on opposing faces of the IFN-beta enhancer DNA, should result in deformation of the DNA. Analysis of the characteristics of binding of the monomeric and dimeric IRF-3 to the enhancer DNA indeed showed that formation of this complex requires considerable work for deformation of its components, most likely bending of the DNA. Such bending was confirmed by atomic force microscopy of dimeric IRF-3 bound to the PRDII-PRDI tandem recognition sites placed at the middle of a 300 bp DNA probe. Bending of DNA by IRF-3 must be significant in the assembly and function of the IFN-beta enhancer.
C1 [Shukla, Hem; Vaitiekunas, Paulius; Majumdar, Ananya K.; Dragan, Anatoly I.; Crane-Robinson, Colyn; Privalov, Peter L.] Johns Hopkins Univ, Dept Biol, Baltimore, MD 21218 USA.
[Dragan, Anatoly I.] Univ Maryland, Inst Fluorescence, Baltimore, MD 21201 USA.
[Dimitriadis, Emilios K.; Kotova, Svetlana] NIH, Bethesda, MD 20892 USA.
[Crane-Robinson, Colyn] Univ Portsmouth, Sch Biol Sci, Biophys Grp, Portsmouth, Hants, England.
RP Crane-Robinson, C (reprint author), Johns Hopkins Univ, Dept Biol, Baltimore, MD 21218 USA.
EM colyn.crane-robinson@port.ac.uk
FU NIH [105365]
FX The authors wish to acknowledge NIH grant 105365, entitled "The
mechanism of Interferon Regulatory Factor (IRF) Activation".
NR 27
TC 4
Z9 4
U1 0
U2 2
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0006-2960
J9 BIOCHEMISTRY-US
JI Biochemistry
PD AUG 14
PY 2012
VL 51
IS 32
BP 6320
EP 6327
DI 10.1021/bi300260s
PG 8
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 988GY
UT WOS:000307478700005
PM 22812703
ER
PT J
AU Coon, SL
Munson, PJ
Cherukuri, PF
Sugden, D
Rath, MF
Moller, M
Clokie, SJH
Fu, C
Olanich, ME
Rangel, Z
Werner, T
Mullikin, JC
Klein, DC
AF Coon, Steven L.
Munson, Peter J.
Cherukuri, Praveen F.
Sugden, David
Rath, Martin F.
Moller, Morten
Clokie, Samuel J. H.
Fu, Cong
Olanich, Mary E.
Rangel, Zoila
Werner, Thomas
Mullikin, James C.
Klein, David C.
CA NISC Comparative Sequencing Progra
TI Circadian changes in long noncoding RNAs in the pineal gland
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE RNA sequencing; neuroendocrine regulation; differential expression;
chronobiology
ID RAT PINEALOCYTES; GENE-EXPRESSION; ADENOSINE-3',5'-MONOPHOSPHATE;
TRANSCRIPTION; REVEALS; DIFFERENTIATION; COMPLEXES; MECHANISM;
MELATONIN; RHYTHMS
AB Long noncoding RNAs (lncRNAs) play a broad range of biological roles, including regulation of expression of genes and chromosomes. Here, we present evidence that lncRNAs are involved in vertebrate circadian biology. Differential night/day expression of 112 lncRNAs (0.3 to >50 kb) occurs in the rat pineal gland, which is the source of melatonin, the hormone of the night. Approximately one-half of these changes reflect nocturnal increases. Studies of eight lncRNAs with 2- to >100-fold daily rhythms indicate that, in most cases, the change results from neural stimulation from the central circadian oscillator in the suprachiasmatic nucleus (doubling time = 0.5-1.3 h). Light exposure at night rapidly reverses (halving time = 9-32 min) levels of some of these lncRNAs. Organ culture studies indicate that expression of these lncRNAs is regulated by norepinephrine acting through cAMP. These findings point to a dynamic role of lncRNAs in the circadian system.
C1 [Coon, Steven L.; Clokie, Samuel J. H.; Fu, Cong; Olanich, Mary E.; Klein, David C.] NHGRI, Sect Neuroendocrinol, Program Dev Endocrinol & Genet,NIH, Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD 20892 USA.
[Munson, Peter J.; Rangel, Zoila] NHGRI, Math & Stat Comp Lab, Ctr Informat Technol, NIH, Bethesda, MD 20892 USA.
[Cherukuri, Praveen F.; Mullikin, James C.] NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA.
[Cherukuri, Praveen F.; Mullikin, James C.; NISC Comparative Sequencing Progra] NHGRI, Intramural Sequencing Ctr, NIH, Bethesda, MD 20852 USA.
[Sugden, David] Kings Coll London, Sch Med, Div Womens Hlth, London SE1 1UL, England.
[Rath, Martin F.; Moller, Morten] Univ Copenhagen, Panum Inst, Dept Neurosci & Pharmacol, DK-2200 Copenhagen, Denmark.
[Werner, Thomas] Genomatix Software GmbH, D-80335 Munich, Germany.
[Werner, Thomas] Univ Michigan, Ann Arbor, MI 48109 USA.
RP Klein, DC (reprint author), NHGRI, Sect Neuroendocrinol, Program Dev Endocrinol & Genet,NIH, Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD 20892 USA.
EM klein@helix.nih.gov
OI Clokie, Samuel/0000-0002-0025-3652; Rath, Martin/0000-0002-4047-6324
FU National Institute of Child Health and Human Development, National
Institutes of Health; Center for Information Technology, National
Institutes of Health; National Human Genome Research Institute, National
Institutes of Health; Biotechnology and Biological Sciences Research
Council United Kingdom; Danish Medical Research Council; Lundbeck
Foundation; Novo Nordisk Foundation; Carlsberg Foundation; Simon Fougner
Hartmanns Familiefond
FX We thank Ms. Tine Thorup Mellergaard for expert technical assistance.
This work was supported, in whole or in part, by the Intramural Research
Programs of the National Institute of Child Health and Human
Development, National Institutes of Health (S. L. C., S.J.H.C., C. F.,
M.E.O. and D. C. K.), the Center for Information Technology, National
Institutes of Health (P.J.M. and Z.R.), and the National Human Genome
Research Institute, National Institutes of Health (P. F. C. and J.C.
M.); the Biotechnology and Biological Sciences Research Council United
Kingdom (D. S.); the Danish Medical Research Council (M. F. R.); the
Lundbeck Foundation (M. F. R. and M. M.); and the Novo Nordisk
Foundation, the Carlsberg Foundation, and the Simon Fougner Hartmanns
Familiefond (M. M.).
NR 46
TC 28
Z9 33
U1 2
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 14
PY 2012
VL 109
IS 33
BP 13319
EP 13324
DI 10.1073/pnas.1207748109
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 992VC
UT WOS:000307807000043
PM 22864914
ER
PT J
AU Qin, LZ
Liu, XB
Sun, QF
Fan, ZP
Xia, DS
Ding, G
Ong, HL
Adams, D
Gahl, WA
Zheng, CY
Qi, SR
Jin, LY
Zhang, CM
Gu, LK
He, JQ
Deng, DJ
Ambudkar, IS
Wang, SL
AF Qin, Lizheng
Liu, Xibao
Sun, Qifei
Fan, Zhipeng
Xia, Dengsheng
Ding, Gang
Ong, Hwei Ling
Adams, David
Gahl, William A.
Zheng, Changyu
Qi, Senrong
Jin, Luyuan
Zhang, Chunmei
Gu, Liankun
He, Junqi
Deng, Dajun
Ambudkar, Indu S.
Wang, Songlin
TI Sialin (SLC17A5) functions as a nitrate transporter in the plasma
membrane
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE pH; proton
ID ACID STORAGE DISORDERS; NITRIC-OXIDE; ANION TRANSPORTER; HUMAN
CIRCULATION; DIETARY NITRATE; EXPRESSION; METABOLISM; CHL1; SALIVARY;
DISEASES
AB In vivo recycling of nitrate (NO3-) and nitrite (NO2-) is an important alternative pathway for the generation of nitric oxide (NO) and maintenance of systemic nitrate-nitrite-NO balance. More than 25% of the circulating NO3- is actively removed and secreted by salivary glands. Oral commensal bacteria convert salivary NO3- to NO2-, which enters circulation and leads to NO generation. The transporters for NO3- in salivary glands have not yet been identified. Here we report that sialin (SLC17A5), mutations in which cause Salla disease and infantile sialic acid storage disorder (ISSD), functions as an electrogenic 2NO(3)(-)/H+ cotransporter in the plasma membrane of salivary gland acinar cells. We have identified an extracellular pH-dependent anion current that is carried by NO3- or sialic acid (SA), but not by Br-, and is accompanied by intracellular acidification. Both responses were reduced by knockdown of sialin expression and increased by the plasma membrane-targeted sialin mutant (L22A-L23A). Fibroblasts from patients with ISSD displayed reduced SA- and NO3--induced currents compared with healthy controls. Furthermore, expression of disease-associated sialin mutants in fibroblasts and salivary gland cells suppressed the H+-dependent NO3- conductance. Importantly, adenovirus-dependent expression of the sialinH183R mutant in vivo in pig salivary glands decreased NO3- secretion in saliva after intake of a NO3--rich diet. Taken together, these data demonstrate that sialin mediates nitrate influx into salivary gland and other cell types. We suggest that the 2NO(3)(-)/H+ transport function of sialin in salivary glands can contribute significantly to clearance of serum nitrate, as well as nitrate recycling and physiological nitrite-NO homeostasis.
C1 [Gu, Liankun; Deng, Dajun] Peking Univ, Canc Hosp & Inst, Key Lab Carcinogenesis & Translat Res, Beijing 100142, Peoples R China.
[Qin, Lizheng; Sun, Qifei; Fan, Zhipeng; Xia, Dengsheng; Ding, Gang; Qi, Senrong; Jin, Luyuan; Zhang, Chunmei; Wang, Songlin] Capital Med Univ, Sch Stomatol, Salivary Gland Dis Ctr, Beijing 100050, Peoples R China.
[Qin, Lizheng; Sun, Qifei; Fan, Zhipeng; Xia, Dengsheng; Ding, Gang; Qi, Senrong; Jin, Luyuan; Zhang, Chunmei; Wang, Songlin] Capital Med Univ, Sch Stomatol, Beijing Key Lab Tooth Regenerat & Funct Reconstru, Beijing 100050, Peoples R China.
[Liu, Xibao; Ong, Hwei Ling; Zheng, Changyu; Ambudkar, Indu S.] Natl Inst Dent & Craniofacial Res, Mol Physiol & Therapeut Branch, Bethesda, MD 20892 USA.
[Adams, David; Gahl, William A.] NHGRI, Med Genet Branch, Bethesda, MD 20892 USA.
[He, Junqi; Wang, Songlin] Capital Med Univ, Sch Basic Med, Dept Biochem & Mol Biol, Beijing 100069, Peoples R China.
RP Deng, DJ (reprint author), Peking Univ, Canc Hosp & Inst, Key Lab Carcinogenesis & Translat Res, Beijing 100142, Peoples R China.
EM dengdajun@bjmu.edu.cn; iambudkar@dir.nidcr.nih.gov; slwang@ccmu.edu.cn
RI Deng, Dajun/D-4605-2009
OI Deng, Dajun/0000-0001-5161-5943
FU National Nature Science Foundation of China [30430690, 30125042,
81170975]; National Basic Research Program of China [2007CB947304,
2010CB944801]; Division of Intramural Research of the National Institute
of Dental and Craniofacial Research; Division of Intramural Research of
the National Human Genome Research Institute
FX We thank Dr. Jim Turner, Dr. Shmuel Muallem, Dr. Jing Jiang, and
Professor Liangbiao Chen for their invaluable help during the course of
this work. This study was supported by the National Nature Science
Foundation of China (Grants 30430690, 30125042, and 81170975), the
National Basic Research Program of China (Grants 2007CB947304 and
2010CB944801), and the Divisions of Intramural Research of the National
Institute of Dental and Craniofacial Research and the National Human
Genome Research Institute.
NR 30
TC 36
Z9 37
U1 3
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 14
PY 2012
VL 109
IS 33
BP 13434
EP 13439
DI 10.1073/pnas.1116633109
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 992VC
UT WOS:000307807000063
PM 22778404
ER
PT J
AU Ozen, E
Gozukizil, A
Erdal, E
Uren, A
Bottaro, DP
Atabey, N
AF Ozen, Evin
Gozukizil, Aysim
Erdal, Esra
Uren, Aykut
Bottaro, Donald P.
Atabey, Nese
TI Heparin Inhibits Hepatocyte Growth Factor Induced Motility and Invasion
of Hepatocellular Carcinoma Cells through Early Growth Response Protein
1
SO PLOS ONE
LA English
DT Article
ID TRANSCRIPTION FACTOR EGR-1; FACTOR SCATTER FACTOR; C-MET; FACTOR/SCATTER
FACTOR; SIGNALING PATHWAY; IN-VIVO; MELANOMA-CELLS; UP-REGULATION;
GENE-THERAPY; EXPRESSION
AB The Hepatocyte Growth Factor (HGF)/c-Met signaling pathway regulates hepatocyte proliferation, and pathway aberrations are implicated in the invasive and metastatic behaviors of hepatocellular carcinoma (HCC). In addition to c-Met, heparin acts as a co-receptor to modulate pathway activity. Recently, anti-metastatic and anti-cancer effects of heparin have been reported. However, the role of heparin in the regulation of HGF signaling remains controversial and the effects of heparin on HGF-induced biological responses during hepatocarcinogenesis is not yet defined. In this study we determined the effects of heparin on HGF-induced activities of HCC cells and the underlying molecular mechanisms. Here, we report for the first time that heparin inhibits HGF-induced adhesion, motility and invasion of HCC cells. In addition, heparin reduced HGF-induced activation of c-Met and MAPK in a dose-dependent manner, as well as decreased transcriptional activation and expression of Early growth response factor 1 (Egr1). HGF-induced MMP-2 and MMP-9 activation, and MT1-MMP expression, also were inhibited by heparin. Stable knockdown of Egr1 caused a significant decrease in HGF-induced invasion, as well as the activation and expression of MMPs. Parallel to these findings, the overexpression of Egr1 increased the invasiveness of HCC cells. Our results suggest that Egr1 activates HGF-induced cell invasion through the regulation of MMPs in HCC cells and heparin inhibits HGF-induced cellular invasion via the downregulation of Egr1. Therefore, heparin treatment might be a therapeutic approach to inhibit invasion and metastasis of HCC, especially for patients with active HGF/c-Met signaling.
C1 [Ozen, Evin; Gozukizil, Aysim; Erdal, Esra; Atabey, Nese] Dokuz Eylul Univ, Dept Med Biol & Genet, Sch Med, Izmir, Turkey.
[Uren, Aykut] Georgetown Univ, Med Ctr, Lombardi Comprehens Canc Ctr, Washington, DC 20007 USA.
[Bottaro, Donald P.] NCI, Urol Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Ozen, E (reprint author), Dokuz Eylul Univ, Dept Med Biol & Genet, Sch Med, Izmir, Turkey.
EM nese.atabey@deu.edu.tr
RI Bottaro, Donald/F-8550-2010
OI Bottaro, Donald/0000-0002-5057-5334
FU Turkish Scientific and Technological Research Council (TUBITAK) [SBAG -
110S349]; Dokuz Eylul University Research Foundation [2008-KB-SAG-02];
Intramural Research Program of the NIH, National Cancer Institute,
Center for Cancer Research; Cancer Center Support Grant from NIH/NCI
[P30 CA051008]
FX This project was funded by grants to Prof. Dr. Atabey from Turkish
Scientific and Technological Research Council (TUBITAK, SBAG - 110S349)
and Dokuz Eylul University Research Foundation (2008-KB-SAG-02). This
work was also supported in part by the Intramural Research Program of
the NIH, National Cancer Institute, Center for Cancer Research and by
the Cancer Center Support Grant (P30 CA051008) from NIH/NCI for the use
of Biacore Molecular Interaction Shared Resource. The funders had no
role in study design, data collection and analysis, decision to publish,
or preparation of the manuscript.
NR 61
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U1 1
U2 9
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD AUG 13
PY 2012
VL 7
IS 8
AR e42717
DI 10.1371/journal.pone.0042717
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 988OJ
UT WOS:000307500100023
PM 22912725
ER
PT J
AU Pitzer, VE
Atkins, KE
de Blasio, BF
Van Effelterre, T
Atchison, CJ
Harris, JP
Shim, E
Galvani, AP
Edmunds, WJ
Viboud, C
Patel, MM
Grenfell, BT
Parashar, UD
Lopman, BA
AF Pitzer, Virginia E.
Atkins, Katherine E.
de Blasio, Birgitte Freiesleben
Van Effelterre, Thierry
Atchison, Christina J.
Harris, John P.
Shim, Eunha
Galvani, Alison P.
Edmunds, W. John
Viboud, Cecile
Patel, Manish M.
Grenfell, Bryan T.
Parashar, Umesh D.
Lopman, Ben A.
TI Direct and Indirect Effects of Rotavirus Vaccination: Comparing
Predictions from Transmission Dynamic Models
SO PLOS ONE
LA English
DT Article
ID INFECTIOUS INTESTINAL DISEASE; 1ST 2 YEARS; UNITED-STATES;
GENERAL-PRACTICE; DOUBLE-BLIND; IMPACT; GASTROENTERITIS; EFFICACY;
PROTECTION; CHILDREN
AB Early observations from countries that have introduced rotavirus vaccination suggest that there may be indirect protection for unvaccinated individuals, but it is unclear whether these benefits will extend to the long term. Transmission dynamic models have attempted to quantify the indirect protection that might be expected from rotavirus vaccination in developed countries, but results have varied. To better understand the magnitude and sources of variability in model projections, we undertook a comparative analysis of transmission dynamic models for rotavirus. We fit five models to reported rotavirus gastroenteritis (RVGE) data from England and Wales, and evaluated outcomes for short- and long-term vaccination effects. All of our models reproduced the important features of rotavirus epidemics in England and Wales. Models predicted that during the initial year after vaccine introduction, incidence of severe RVGE would be reduced 1.8-2.9 times more than expected from the direct effects of the vaccine alone (28-50% at 90% coverage), but over a 5-year period following vaccine introduction severe RVGE would be reduced only by 1.1-1.7 times more than expected from the direct effects (54-90% at 90% coverage). Projections for the long-term reduction of severe RVGE ranged from a 55% reduction at full coverage to elimination with at least 80% coverage. Our models predicted short-term reductions in the incidence of RVGE that exceeded estimates of the direct effects, consistent with observations from the United States and other countries. Some of the models predicted that the short-term indirect benefits may be offset by a partial shifting of the burden of RVGE to older unvaccinated individuals. Nonetheless, even when such a shift occurs, the overall reduction in severe RVGE is considerable. Discrepancies among model predictions reflect uncertainties about age variation in the risk and reporting of RVGE, and the duration of natural and vaccine-induced immunity, highlighting important questions for future research.
C1 [Pitzer, Virginia E.; Grenfell, Bryan T.] Princeton Univ, Dept Ecol & Evolut Biol, Princeton, NJ 08544 USA.
[Pitzer, Virginia E.; Viboud, Cecile; Grenfell, Bryan T.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Pitzer, Virginia E.; Atkins, Katherine E.; Galvani, Alison P.] Yale Univ, Dept Epidemiol Microbial Dis, Sch Publ Hlth, New Haven, CT 06520 USA.
[de Blasio, Birgitte Freiesleben] Univ Oslo, Dept Biostat, Inst Basic Med Sci, Oslo, Norway.
[de Blasio, Birgitte Freiesleben] Norwegian Inst Publ Hlth, Dept Infect Dis Epidemiol, Oslo, Norway.
[Van Effelterre, Thierry] GlaxoSmithKline Biol, Global Vaccine Dev, Wavre, Belgium.
[Atchison, Christina J.; Edmunds, W. John] London Sch Hyg & Trop Med, Infect Dis Epidemiol Unit, Dept Epidemiol & Populat Hlth, London WC1, England.
[Harris, John P.] Hlth Protect Agcy, Ctr Infect, Dept Gastrointestinal Emerging & Zoonot Infect, London, England.
[Shim, Eunha] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA.
[Patel, Manish M.; Parashar, Umesh D.; Lopman, Ben A.] Ctr Dis Control & Prevent, Epidemiol Branch, Div Viral Dis, Natl Ctr Immunizat & Resp Dis, Atlanta, GA USA.
RP Pitzer, VE (reprint author), Yale Univ, Dept Epidemiol Microbial Dis, Sch Publ Hlth, New Haven, CT 06520 USA.
EM virginia.pitzer@yale.edu
OI Atchison, Christina/0000-0001-8304-7389; Pitzer,
Virginia/0000-0003-1015-2289
FU National Institutes of Health [R01 GM083983-01]; Bill and Melinda Gates
Foundation; Miriam Weston Trust; RAPIDD program of the Science &
Technology Directorate, Department of Homeland Security and the Fogarty
International Center, National Institutes of Health; GAVI Alliance under
a collaborative agreement with the Program for Appropriate Technology in
Health (PATH)
FX This work was supported by the National Institutes of Health (R01
GM083983-01) (V.E.P. and B.T.G.), the Bill and Melinda Gates Foundation
(V.E.P. and B.T.G.), Miriam Weston Trust (K.E.A. and A.P.G.), the RAPIDD
program of the Science & Technology Directorate, Department of Homeland
Security and the Fogarty International Center, National Institutes of
Health (V.E.P, B.T.G., K.E.A., and B.F.B.), and the GAVI Alliance under
a collaborative agreement with the Program for Appropriate Technology in
Health (PATH) (M.M.P., U.D.P., and B.A.L.). The findings and conclusions
in this report are those of the authors and do not necessarily represent
the views of the Centers for Disease Control and Prevention (CDC). The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 51
TC 17
Z9 17
U1 0
U2 11
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD AUG 13
PY 2012
VL 7
IS 8
AR e42320
DI 10.1371/journal.pone.0042320
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 988OJ
UT WOS:000307500100011
PM 22912699
ER
PT J
AU Jeang, KT
AF Jeang, Kuan-Teh
TI Open access, moving to the fore
SO RETROVIROLOGY
LA English
DT Editorial Material
ID MOUSE DNA; XMRV; CONTAMINATION; SEQUENCES
AB Nine years after its founding, Retrovirology has moved to the forefront of virology journals in Impact Factor.
C1 Natl Inst Hlth, Bethesda, MD 20892 USA.
RP Jeang, KT (reprint author), Natl Inst Hlth, Bethesda, MD 20892 USA.
EM kjeang@nih.gov
NR 11
TC 0
Z9 0
U1 0
U2 9
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 13
PY 2012
VL 9
AR 66
DI 10.1186/1742-4690-9-66
PG 2
WC Virology
SC Virology
GA 993AD
UT WOS:000307823300001
PM 22889251
ER
PT J
AU Zonderman, AB
Evans, MK
AF Zonderman, Alan B.
Evans, Michele K.
TI Improving Patients' Quality of Life at the End of Life
SO ARCHIVES OF INTERNAL MEDICINE
LA English
DT Editorial Material
ID PERSONALITY; CANCER; CARE
C1 [Zonderman, Alan B.; Evans, Michele K.] NIA, Intramural Res Program, Biomed Res Ctr, NIH, Baltimore, MD 21224 USA.
RP Zonderman, AB (reprint author), NIA, Intramural Res Program, Biomed Res Ctr, NIH, 251 Bayview Blvd, Baltimore, MD 21224 USA.
EM zondermana@mail.nih.gov
OI Zonderman, Alan B/0000-0002-6523-4778
FU Intramural NIH HHS [Z01 AG000513-07]
NR 11
TC 1
Z9 1
U1 1
U2 6
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA
SN 0003-9926
J9 ARCH INTERN MED
JI Arch. Intern. Med.
PD AUG 13
PY 2012
VL 172
IS 15
BP 1142
EP 1144
DI 10.1001/archinternmed.2012.3169
PG 3
WC Medicine, General & Internal
SC General & Internal Medicine
GA 986TT
UT WOS:000307369200008
PM 22777572
ER
PT J
AU Pattakos, G
Koch, CG
Brizzio, ME
Batizy, LH
Sabik, JF
Blackstone, EH
Lauer, MS
AF Pattakos, Gregory
Koch, Colleen G.
Brizzio, Mariano E.
Batizy, Lillian H.
Sabik, Joseph F., III
Blackstone, Eugene H.
Lauer, Michael S.
TI Outcome of Patients Who Refuse Transfusion After Cardiac Surgery A
Natural Experiment With Severe Blood Conservation
SO ARCHIVES OF INTERNAL MEDICINE
LA English
DT Article
ID OPEN-HEART-SURGERY; JEHOVAHS-WITNESSES; CARDIOVASCULAR-SURGERY;
OPERATIONS; MORBIDITY; BYPASS; RISK; CELL; MORTALITY
AB Background: Jehovah's Witness patients (Witnesses) who undergo cardiac surgery provide a unique natural experiment in severe blood conservation because anemia, transfusion, erythropoietin, and antifibrinolytics have attendant risks. Our objective was to compare morbidity and long-term survival of Witnesses undergoing cardiac surgery with a similarly matched group of patients who received transfusions.
Methods: A total of 322 Witnesses and 87 453 non-Witnesses underwent cardiac surgery at our center from January 1, 1983, to January 1, 2011. All Witnesses prospectively refused blood transfusions. Among non-Witnesses, 38 467 did not receive blood transfusions and 48 986 did. We used propensity methods to match patient groups and parametric multiphase hazard methods to assess long-term survival. Our main outcome measures were postoperative morbidity complications, in-hospital mortality, and long-term survival.
Results: Witnesses had fewer acute complications and shorter length of stay than matched patients who received transfusions: myocardial infarction, 0.31% vs 2.8% (P=.01); additional operation for bleeding, 3.7% vs 7.1% (P=.03); prolonged ventilation, 6% vs 16% (P<.001); intensive care unit length of stay (15th, 50th, and 85th percentiles), 24, 25, and 72 vs 24, 48, and 162 hours (P<.001); and hospital length of stay (15th, 50th, and 85th percentiles), 5, 7, and 11 vs 6, 8, and 16 days (P<.001). Witnesses had better 1-year survival (95%; 95% CI, 93%-96%; vs 89%; 95% Cl, 87%-90%; P=.007) but similar 20-year survival (34%; 95% CI, 31%-38%; vs 32% 95% CI, 28%-35%; P=.90).
Conclusions: Witnesses do not appear to be at increased risk for surgical complications or long-term mortality when comparisons are properly made by transfusion status. Thus, current extreme blood management strategies do not appear to place patients at heightened risk for reduced long-term survival.
C1 [Koch, Colleen G.] Cleveland Clin, Dept Cardiothorac Anesthesia, Cleveland, OH 44195 USA.
[Pattakos, Gregory; Brizzio, Mariano E.; Sabik, Joseph F., III; Blackstone, Eugene H.] Cleveland Clin, Inst Heart & Vasc, Dept Thorac & Cardiovasc Surg, Cleveland, OH 44195 USA.
[Koch, Colleen G.] Cleveland Clin, Qual & Patient Safety Inst, Cleveland, OH 44195 USA.
[Batizy, Lillian H.; Blackstone, Eugene H.] Cleveland Clin, Res Inst, Dept Quantitat Hlth Sci, Cleveland, OH 44195 USA.
[Lauer, Michael S.] NHLBI, Div Cardiovasc Sci, NIH, Bethesda, MD 20892 USA.
RP Koch, CG (reprint author), Cleveland Clin, Dept Cardiothorac Anesthesia, 9500 Euclid Ave,J4-245, Cleveland, OH 44195 USA.
EM kochc@ccf.org
RI Lauer, Michael/L-9656-2013
OI Lauer, Michael/0000-0002-9217-8177
FU National Institutes of Health [1U01HL088955-01]
FX This study was supported in part by the Kenneth Gee and Paula Shaw, PhD,
Chair in Heart Research, held by Dr Blackstone. Dr Pattakos is a
National Heart, Lung and Blood Institute Clinical Research Scholar of
the Cardiothoracic Surgical Trials Network, and his master of science in
clinical research has been funded by grant 1U01HL088955-01 from the
National Institutes of Health.
NR 25
TC 44
Z9 44
U1 0
U2 6
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA
SN 0003-9926
J9 ARCH INTERN MED
JI Arch. Intern. Med.
PD AUG 13
PY 2012
VL 172
IS 15
BP 1154
EP 1160
DI 10.1001/archinternmed.2012.2449
PG 7
WC Medicine, General & Internal
SC General & Internal Medicine
GA 986TT
UT WOS:000307369200012
PM 22751620
ER
PT J
AU Voight, BF
Peloso, GM
Orho-Melander, M
Frikke-Schmidt, R
Barbalic, M
Jensen, MK
Hindy, G
Holm, H
Ding, EL
Johnson, T
Schunkert, H
Samani, NJ
Clarke, R
Hopewell, JC
Thompson, JF
Li, MY
Thorleifsson, G
Newton-Cheh, C
Musunuru, K
Pirruccello, JP
Saleheen, D
Chen, L
Stewart, AFR
Schillert, A
Thorsteinsdottir, U
Thorgeirsson, G
Anand, S
Engert, JC
Morgan, T
Spertus, J
Stoll, M
Berger, K
Martinelli, N
Girelli, D
McKeown, PP
Patterson, CC
Epstein, SE
Devaney, J
Burnett, MS
Mooser, V
Ripatti, S
Surakka, I
Nieminen, MS
Sinisalo, J
Lokki, ML
Perola, M
Havulinna, A
de Faire, U
Gigante, B
Ingelsson, E
Zeller, T
Wild, P
de Bakker, PIW
Klungel, OH
Maitland-van der Zee, AH
Peters, BJM
de Boer, A
Grobbee, DE
Kamphuisen, PW
Deneer, VHM
Elbers, CC
Onland-Moret, NC
Hofker, MH
Wijmenga, C
Verschuren, WMM
Boer, JMA
van der Schouw, YT
Rasheed, A
Frossard, P
Demissie, S
Willer, C
Do, R
Ordovas, JM
Abecasis, GR
Boehnke, M
Mohlke, KL
Daly, MJ
Guiducci, C
Burtt, NP
Surti, A
Gonzalez, E
Purcell, S
Gabriel, S
Marrugat, J
Peden, J
Erdmann, J
Diemert, P
Willenborg, C
Konig, IR
Fischer, M
Hengstenberg, C
Ziegler, A
Buysschaert, I
Lambrechts, D
Van de Werf, F
Fox, KA
El Mokhtari, NE
Rubin, D
Schrezenmeir, J
Schreiber, S
Schafer, A
Danesh, J
Blankenberg, S
Roberts, R
McPherson, R
Watkins, H
Hall, AS
Overvad, K
Rimm, E
Boerwinkle, E
Tybjaerg-Hansen, A
Cupples, LA
Reilly, MP
Melander, O
Mannucci, PM
Ardissino, D
Siscovick, D
Elosua, R
Stefansson, K
O'Donnell, CJ
Salomaa, V
Rader, DJ
Peltonen, L
Schwartz, SM
Altshuler, D
Kathiresan, S
AF Voight, Benjamin F.
Peloso, Gina M.
Orho-Melander, Marju
Frikke-Schmidt, Ruth
Barbalic, Maja
Jensen, Majken K.
Hindy, George
Holm, Hilma
Ding, Eric L.
Johnson, Toby
Schunkert, Heribert
Samani, Nilesh J.
Clarke, Robert
Hopewell, Jemma C.
Thompson, John F.
Li, Mingyao
Thorleifsson, Gudmar
Newton-Cheh, Christopher
Musunuru, Kiran
Pirruccello, James P.
Saleheen, Danish
Chen, Li
Stewart, Alexandre F. R.
Schillert, Arne
Thorsteinsdottir, Unnur
Thorgeirsson, Gudmundur
Anand, Sonia
Engert, James C.
Morgan, Thomas
Spertus, John
Stoll, Monika
Berger, Klaus
Martinelli, Nicola
Girelli, Domenico
McKeown, Pascal P.
Patterson, Christopher C.
Epstein, Stephen E.
Devaney, Joseph
Burnett, Mary-Susan
Mooser, Vincent
Ripatti, Samuli
Surakka, Ida
Nieminen, Markku S.
Sinisalo, Juha
Lokki, Marja-Liisa
Perola, Markus
Havulinna, Aki
de Faire, Ulf
Gigante, Bruna
Ingelsson, Erik
Zeller, Tanja
Wild, Philipp
de Bakker, Paul I. W.
Klungel, Olaf H.
Maitland-van der Zee, Anke-Hilse
Peters, Bas J. M.
de Boer, Anthonius
Grobbee, Diederick E.
Kamphuisen, Pieter W.
Deneer, Vera H. M.
Elbers, Clara C.
Onland-Moret, N. Charlotte
Hofker, Marten H.
Wijmenga, Cisca
Verschuren, W. M. Monique
Boer, Jolanda M. A.
van der Schouw, Yvonne T.
Rasheed, Asif
Frossard, Philippe
Demissie, Serkalem
Willer, Cristen
Do, Ron
Ordovas, Jose M.
Abecasis, Goncalo R.
Boehnke, Michael
Mohlke, Karen L.
Daly, Mark J.
Guiducci, Candace
Burtt, Noel P.
Surti, Aarti
Gonzalez, Elena
Purcell, Shaun
Gabriel, Stacey
Marrugat, Jaume
Peden, John
Erdmann, Jeanette
Diemert, Patrick
Willenborg, Christina
Koenig, Inke R.
Fischer, Marcus
Hengstenberg, Christian
Ziegler, Andreas
Buysschaert, Ian
Lambrechts, Diether
Van de Werf, Frans
Fox, Keith A.
El Mokhtari, Nour Eddine
Rubin, Diana
Schrezenmeir, Juergen
Schreiber, Stefan
Schaefer, Arne
Danesh, John
Blankenberg, Stefan
Roberts, Robert
McPherson, Ruth
Watkins, Hugh
Hall, Alistair S.
Overvad, Kim
Rimm, Eric
Boerwinkle, Eric
Tybjaerg-Hansen, Anne
Cupples, L. Adrienne
Reilly, Muredach P.
Melander, Olle
Mannucci, Pier M.
Ardissino, Diego
Siscovick, David
Elosua, Roberto
Stefansson, Kari
O'Donnell, Christopher J.
Salomaa, Veikko
Rader, Daniel J.
Peltonen, Leena
Schwartz, Stephen M.
Altshuler, David
Kathiresan, Sekar
TI Plasma HDL cholesterol and risk of myocardial infarction: a mendelian
randomisation study
SO LANCET
LA English
DT Article
ID HIGH-DENSITY-LIPOPROTEIN; CORONARY-HEART-DISEASE; ISCHEMIC
CARDIOVASCULAR-DISEASE; ENDOTHELIAL LIPASE; BLOOD CHOLESTEROL;
GENETIC-VARIANTS; ARTERY-DISEASE; LOCI; ATHEROSCLEROSIS; METAANALYSIS
AB Background High plasma HDL cholesterol is associated with reduced risk of myocardial infarction, but whether this association is causal is unclear. Exploiting the fact that genotypes are randomly assigned at meiosis, are independent of non-genetic confounding, and are unmodified by disease processes, mendelian randomisation can be used to test the hypothesis that the association of a plasma biomarker with disease is causal.
Methods We performed two mendelian randomisation analyses. First, we used as an instrument a single nucleotide polymorphism (SNP) in the endothelial lipase gene (LIPG Asn396Ser) and tested this SNP in 20 studies (20 913 myocardial infarction cases, 95 407 controls). Second, we used as an instrument a genetic score consisting of 14 common SNPs that exclusively associate with HDL cholesterol and tested this score in up to 12 482 cases of myocardial infarction and 41 331 controls. As a positive control, we also tested a genetic score of 13 common SNPs exclusively associated with LDL cholesterol.
Findings Carriers of the LIPG 396Ser allele (2.6% frequency) had higher HDL cholesterol (0.14 mmol/L higher, p=8x10(-13)) but similar levels of other lipid and non-lipid risk factors for myocardial infarction compared with non-carriers. This difference in HDL cholesterol is expected to decrease risk of myocardial infarction by 13% (odds ratio [OR] 0.87, 95% CI 0.84-0.91). However, we noted that the 396Ser allele was not associated with risk of myocardial infarction (OR 0.99, 95% CI 0.88-1.11, p=0.85). From observational epidemiology, an increase of 1 SD in HDL cholesterol was associated with reduced risk of myocardial infarction (OR 0.62, 95% CI 0.58-0.66). However, a 1 SD increase in HDL cholesterol due to genetic score was not associated with risk of myocardial infarction (OR 0.93, 95% CI 0.68-1.26, p=0.63). For LDL cholesterol, the estimate from observational epidemiology (a 1 SD increase in LDL cholesterol associated with OR 1.54, 95% CI 1.45-1.63) was concordant with that from genetic score (OR 2.13, 95% CI 1.69-2.69, p=2x10(-10)).
Interpretation Some genetic mechanisms that raise plasma HDL cholesterol do not seem to lower risk of myocardial infarction. These data challenge the concept that raising of plasma HDL cholesterol will uniformly translate into reductions in risk of myocardial infarction.
C1 [Kathiresan, Sekar] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Human Genet Res, Boston, MA 02114 USA.
[Kathiresan, Sekar] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr, Boston, MA 02114 USA.
[Voight, Benjamin F.] Univ Penn, Dept Pharmacol, Philadelphia, PA 19104 USA.
[Voight, Benjamin F.] Univ Penn, Dept Genet, Philadelphia, PA 19104 USA.
[Altshuler, David] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA.
[Newton-Cheh, Christopher; O'Donnell, Christopher J.; Kathiresan, Sekar] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA.
[Voight, Benjamin F.; Newton-Cheh, Christopher; Musunuru, Kiran; Pirruccello, James P.; de Bakker, Paul I. W.; Daly, Mark J.; Guiducci, Candace; Burtt, Noel P.; Surti, Aarti; Gonzalez, Elena; Purcell, Shaun; Gabriel, Stacey; Altshuler, David; Kathiresan, Sekar] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA.
[Peloso, Gina M.; Demissie, Serkalem; Cupples, L. Adrienne] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Peloso, Gina M.; Demissie, Serkalem; Cupples, L. Adrienne; O'Donnell, Christopher J.] NHLBI, Framingham Heart Study, Framingham, MA USA.
[Melander, Olle] Lund Univ, Skania Univ Hosp, Dept Clin Sci Hypertens & Cardiovasc Dis, Malmo, Sweden.
[Frikke-Schmidt, Ruth; Tybjaerg-Hansen, Anne] Copenhagen Univ Hosp, Rigshosp, Dept Clin Biochem, Mol Genet Sect, Copenhagen, Denmark.
[Barbalic, Maja; Boerwinkle, Eric] Univ Texas Hlth Sci Ctr Houston, Ctr Human Genet, Houston, TX USA.
[Jensen, Majken K.; Rimm, Eric] Harvard Univ, Sch Publ Hlth, Dept Nutr & Epidemiol, Boston, MA 02115 USA.
[Ding, Eric L.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
[Ding, Eric L.; Rimm, Eric] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA.
[Holm, Hilma; Thorleifsson, Gudmar; Thorsteinsdottir, Unnur; Stefansson, Kari] deCODE Genet, Reykjavik, Iceland.
[Johnson, Toby] Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, Genome Ctr, London, England.
[Schunkert, Heribert; Erdmann, Jeanette; Diemert, Patrick] Med Univ Lubeck, Med Klin 2, D-23538 Lubeck, Germany.
[Schillert, Arne; Willenborg, Christina; Koenig, Inke R.; Ziegler, Andreas] Med Univ Lubeck, Inst Med Biometrie & Stat, D-23538 Lubeck, Germany.
[Samani, Nilesh J.] Univ Leicester, Dept Cardiovasc Sci, Leicester, Leics, England.
[Thompson, John F.] Univ Leicester, Dept Hlth Sci, Leicester, Leics, England.
[Samani, Nilesh J.] Glenfield Gen Hosp, Leicester Natl Inst Hlth Res Biomed Res Unit Card, Leicester LE3 9QP, Leics, England.
[Reilly, Muredach P.; Rader, Daniel J.] Univ Penn, Inst Translat Med & Therapeut, Philadelphia, PA 19104 USA.
[Reilly, Muredach P.; Rader, Daniel J.] Univ Penn, Cardiovasc Inst, Philadelphia, PA 19104 USA.
[Saleheen, Danish; Danesh, John] Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England.
[Chen, Li; Stewart, Alexandre F. R.; Roberts, Robert; McPherson, Ruth] Univ Ottawa, Inst Heart, John & Jennifer Ruddy Canadian Cardiovasc Genet C, Ottawa, ON, Canada.
[Clarke, Robert; Hopewell, Jemma C.] Univ Oxford, Clin Trial Serv Unit, Oxford, England.
[Clarke, Robert; Hopewell, Jemma C.] Univ Oxford, Epidemiol Studies Unit, Oxford, England.
[Peden, John; Watkins, Hugh] Univ Oxford, Dept Cardiovasc Med, Oxford, England.
[Thorsteinsdottir, Unnur; Thorgeirsson, Gudmundur; Stefansson, Kari] Univ Iceland, Fac Med, Reykjavik, Iceland.
[Thorgeirsson, Gudmundur] Landspitali Univ Hosp, Div Cardiol, Dept Internal Med, Reykjavik, Iceland.
[Anand, Sonia] McMaster Univ, Populat Hlth Res Inst, Hamilton Hlth Sci, Hamilton, ON, Canada.
[Anand, Sonia] McMaster Univ, Dept Med, Hamilton, ON, Canada.
[Anand, Sonia] McMaster Univ, Dept Clin Epidemiol & Biostat, Hamilton, ON, Canada.
[Engert, James C.] McGill Univ, Dept Med, Montreal, PQ, Canada.
[Engert, James C.] McGill Univ, Dept Human Genet, Montreal, PQ, Canada.
[Morgan, Thomas] Vanderbilt Univ, Sch Med, Dept Pediat, Nashville, TN 37212 USA.
[Spertus, John] St Lukes Hosp, Mid Amer Heart Inst, Kansas City, MO 64111 USA.
[Spertus, John] Univ Missouri, Kansas City, MO 64110 USA.
[Stoll, Monika] Univ Munster, Leibniz Inst Arteriosclerosis Res, Munster, Germany.
[Berger, Klaus] Univ Munster, Inst Epidemiol & Social Med, Munster, Germany.
[Martinelli, Nicola; Girelli, Domenico] Univ Verona, Dept Med, I-37100 Verona, Italy.
[McKeown, Pascal P.; Patterson, Christopher C.] Queens Univ Belfast, Inst Clin Sci, Ctr Publ Hlth, Belfast, Antrim, North Ireland.
[Epstein, Stephen E.; Devaney, Joseph; Burnett, Mary-Susan] Washington Hosp Ctr, MedStar Res Inst, Cardiovasc Res Inst, Washington, DC 20010 USA.
[Mooser, Vincent] GlaxoSmithKline, Div Genet, King Of Prussia, PA USA.
[Mooser, Vincent] GlaxoSmithKline, Drug Discovery, King Of Prussia, PA USA.
[Ripatti, Samuli; Surakka, Ida; Nieminen, Markku S.; Peltonen, Leena] Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki, Finland.
[Nieminen, Markku S.; Sinisalo, Juha] Univ Helsinki, Cent Hosp, Dept Med, Div Cardiol, Helsinki, Finland.
[Lokki, Marja-Liisa] Univ Helsinki, Transplantat Lab, Haartman Inst, Helsinki, Finland.
[Perola, Markus; Havulinna, Aki; Salomaa, Veikko] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Chron Dis Epidemiol & Prevent Unit, Helsinki, Finland.
[Zeller, Tanja] Univ Main 2, Med Klin & Poliklin, Mainz, Germany.
[de Faire, Ulf; Gigante, Bruna; Wild, Philipp; Blankenberg, Stefan] Karolinska Inst, Div Cardiovasc Epidemiol, Stockholm, Sweden.
[de Faire, Ulf; Gigante, Bruna] Karolinska Inst, Inst Environm Med, S-10401 Stockholm, Sweden.
[Ingelsson, Erik] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
[de Bakker, Paul I. W.] Brigham & Womens Hosp, Dept Med, Div Genet, Boston, MA 02115 USA.
[Klungel, Olaf H.; Maitland-van der Zee, Anke-Hilse; Peters, Bas J. M.; de Boer, Anthonius] Univ Utrecht, Utrecht Inst Pharmaceut Sci, Div Pharmacoepidemiol & Clin Pharmacol, NL-3508 TC Utrecht, Netherlands.
[de Bakker, Paul I. W.; Grobbee, Diederick E.; Elbers, Clara C.; Onland-Moret, N. Charlotte; van der Schouw, Yvonne T.] Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands.
[de Bakker, Paul I. W.; Elbers, Clara C.; Onland-Moret, N. Charlotte] Univ Med Ctr Utrecht, Dept Med Genet, Utrecht, Netherlands.
[Kamphuisen, Pieter W.] Univ Groningen, Univ Med Ctr Groningen, Dept Vasc Med, NL-9713 AV Groningen, Netherlands.
[Hofker, Marten H.] Univ Med Ctr Groningen, Dept Pathol & Med Biol, NL-9713 AV Groningen, Netherlands.
[Wijmenga, Cisca] Univ Med Ctr Groningen, Dept Genet, NL-9713 AV Groningen, Netherlands.
[Deneer, Vera H. M.] St Antonius Hosp, Dept Clin Pharm, Nieuwegein, Netherlands.
[Verschuren, W. M. Monique] Natl Inst Publ Hlth & Environm, Ctr Prevent & Hlth Serv Res, NL-3720 BA Bilthoven, Netherlands.
[Boer, Jolanda M. A.] Natl Inst Publ Hlth & Environm, Ctr Nutr & Hlth, NL-3720 BA Bilthoven, Netherlands.
[Willer, Cristen; Abecasis, Goncalo R.; Boehnke, Michael] Univ Michigan, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI 48109 USA.
[Rasheed, Asif; Frossard, Philippe] Ctr Noncommunicable Dis, Karachi, Pakistan.
[Ordovas, Jose M.] Tufts Univ, Nutr & Genom Lab, Jean Mayer United States Dept Agr Human Nutr, Res Ctr Aging, Boston, MA 02111 USA.
[Ordovas, Jose M.] Ctr Nacl Invest Cardiovasc, Dept Cardiovasc Epidemiol & Populat Genet, Madrid, Spain.
[Mohlke, Karen L.] Univ N Carolina, Dept Genet, Chapel Hill, NC USA.
[Marrugat, Jaume; Elosua, Roberto] IMIM, Barcelona, Spain.
[Elosua, Roberto] CIBER Epidemiol & Salud Publ, Barcelona, Spain.
[Fischer, Marcus; Hengstenberg, Christian] Univ Klinikum Regensburg, Klin & Poliklin Innere Med 2, Regensburg, Germany.
[Buysschaert, Ian; Lambrechts, Diether] Univ Hosp Gasthuisberg, Vesalius Res Ctr, VIB KU Leuven, B-3000 Louvain, Belgium.
[Buysschaert, Ian; Lambrechts, Diether; Van de Werf, Frans] Univ Hosp Gasthuisberg, Dept Cardiol, B-3000 Louvain, Belgium.
[Fox, Keith A.] Univ Edinburgh, Div Med & Radiol Sci, Edinburgh, Midlothian, Scotland.
[El Mokhtari, Nour Eddine; Schreiber, Stefan; Schaefer, Arne] Univ Kiel, Inst Klin & Mol Biol, Kiel, Germany.
[Rubin, Diana] Univ Klinikum Schleswig Holstein, Med Klin 1, Kiel, Germany.
[Schrezenmeir, Juergen] Max Rubner Inst, Inst Physiol & Biochem Ernahrung, Kiel, Germany.
[Hall, Alistair S.] Univ Leeds, LIGHT Inst, Fac Med & Hlth, Leeds, W Yorkshire, England.
[Hall, Alistair S.] Univ Leeds, LIMM Res Inst, Fac Med & Hlth, Leeds, W Yorkshire, England.
[Overvad, Kim] Aarhus Univ, Sch Publ Hlth, Dept Epidemiol, Aarhus, Denmark.
[Tybjaerg-Hansen, Anne] Bispebjerg Hosp, Copenhagen City Heart Study, Copenhagen, Denmark.
[Mannucci, Pier M.] IRCCS Fdn Ca Granda Osped Maggiore Policlin, Dept Internal Med & Med Special, Milan, Italy.
[Ardissino, Diego] Azienda Osped Univ Parma, Div Cardiol, Parma, Italy.
[Siscovick, David; Schwartz, Stephen M.] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA.
[Siscovick, David; Schwartz, Stephen M.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
[Peltonen, Leena] Wellcome Trust Sanger Inst Cambridge, Cambridge, England.
[Altshuler, David] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA.
RP Kathiresan, S (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Human Genet Res, Boston, MA 02114 USA.
EM skathiresan@partners.org
RI Ripatti, Samuli/H-9446-2014; Martinelli, Nicola/J-5622-2016; Klungel,
Olaf/I-9563-2016; Konig, Inke/A-4544-2009; Hindy, George/H-1864-2016;
Verdrengh, Evelien/H-4571-2012; Gigante, Bruna/I-9252-2012; Morgan,
Tom/C-3478-2012; Abecasis, Goncalo/B-7840-2010; Altshuler,
David/A-4476-2009; de Bakker, Paul/B-8730-2009; Mannucci,
Pier/C-3102-2014; Schreiber, Stefan/B-6748-2008; Grobbee,
Diederick/C-7651-2014; Wijmenga, Cisca/D-2173-2009; van der Schouw,
Yvonne/F-8327-2014; Willenborg, Christina/D-2668-2012; Onland-Moret, N.
Charlotte/G-9185-2011; Erdmann, Jeanette/P-7513-2014;
OI Ripatti, Samuli/0000-0002-0504-1202; Martinelli,
Nicola/0000-0001-6465-5119; Cupples, L. Adrienne/0000-0003-0273-7965;
Van de Werf, Frans/0000-0001-9479-7767; Willer,
Cristen/0000-0001-5645-4966; ELOSUA, ROBERTO/0000-0001-8235-0095; Ding,
Eric/0000-0002-5881-8097; Johnson, Toby/0000-0002-5998-3270; Hindy,
George/0000-0002-7257-9299; Altshuler, David/0000-0002-7250-4107; de
Bakker, Paul/0000-0001-7735-7858; Schreiber, Stefan/0000-0003-2254-7771;
Grobbee, Diederick/0000-0003-4472-4468; van der Schouw,
Yvonne/0000-0002-4605-435X; Willenborg, Christina/0000-0001-5217-6882;
Abecasis, Goncalo/0000-0003-1509-1825; Stewart,
Alexandre/0000-0003-2673-9164; Erdmann, Jeanette/0000-0002-4486-6231;
Wijmenga, Cisca/0000-0002-5635-1614; Ziegler,
Andreas/0000-0002-8386-5397; Schwartz, Stephen/0000-0001-7499-8502;
Marrugat, Jaume/0000-0003-3320-554X; Watkins, Hugh/0000-0002-5287-9016;
Sinisalo, Juha/0000-0002-0169-5137
FU US National Institutes of Health; Wellcome Trust; European Union;
British Heart Foundation; German Federal Ministry of Education and
Research; Pfizer; Shire Therapeutics; Alnylam Pharmaceuticals; Novartis;
Boehringer Ingelheim; German Migraine & Headache Society (DMKG); Berlin
Chemie; Boots Healthcare; GlaxoSmithKline; McNeil Pharma; MSD Sharp
Dohme
FX US National Institutes of Health, The Wellcome Trust, European Union,
British Heart Foundation, and the German Federal Ministry of Education
and Research.; own stock options in deCODE Genetics, or both. SK serves
on a scientific advisory board for Merck and has received research
grants from Pfizer, Shire Therapeutics, and Alnylam Pharmaceuticals. HS
serves on scientific advisory boards for Merck, Servier, and AstraZeneca
and received lecture fees from Pfizer, Novartis, and Boehringer
Ingelheim. The collection of clinical and sociodemographic data in the
Dortmund Health Study was supported by the German Migraine & Headache
Society (DMKG) and by unrestricted grants of equal share from
AstraZeneca, Berlin Chemie, Boots Healthcare, GlaxoSmithKline, McNeil
Pharma (formerly Woelm Pharma), MSD Sharp & Dohme, and Pfizer to the
University of Muenster. VM, DW, CK, and MW are full-time employees of
GlaxoSmithKline. All other authors declare that they have no conflicts
of interest.
NR 36
TC 720
Z9 729
U1 8
U2 96
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0140-6736
J9 LANCET
JI Lancet
PD AUG 11
PY 2012
VL 380
IS 9841
BP 572
EP 580
DI 10.1016/S0140-6736(12)60312-2
PG 9
WC Medicine, General & Internal
SC General & Internal Medicine
GA 988SQ
UT WOS:000307511400030
PM 22607825
ER
PT J
AU Kim, JH
Wang, AB
Conti, MA
Adelstein, RS
AF Kim, Jong Hyun
Wang, Aibing
Conti, Mary Anne
Adelstein, Robert S.
TI Nonmuscle Myosin II Is Required for Internalization of the Epidermal
Growth Factor Receptor and Modulation of Downstream Signaling
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID EGF RECEPTOR; MEDIATED ENDOCYTOSIS; TYROSINE KINASES; IN-VITRO; PROTEIN;
ACTIVATION; CELLS; ISOFORM; DOMAIN; IDENTIFICATION
AB Ligand-induced internalization of the epidermal growth factor receptor (EGFR) is an important process for regulating signal transduction, cellular dynamics, and cell-cell communication. Here, we demonstrate that nonmuscle myosin II (NM II) is required for the internalization of the EGFR and to trigger the EGFR-dependent activation of ERK and AKT. The EGFR was identified as a protein that interacts with with NM II by co-immunoprecipitation and mass spectrometry analysis. This interaction requires both the regulatory light chain 20 (RLC20) of NM II and the kinase domain of the EGFR. Two paralogs of NM II, NM II-A, and NM II-B can act to internalize the EGFR, depending on the cell type and paralog content of the cell line. Loss (siRNA) or inhibition (25 mu M blebbistatin) of NM II attenuates the internalization of the EGFR and impairs EGFR-dependent activation of ERK and AKT. Both internalization of the EGFR and downstream signaling to ERK and AKT can be partially restored in siRNA-treated cells by introduction of wild type (WT) GFP-NM II, but cannot be restored by motor mutant NM II. Taken together, these results suggest that NM II plays a role in the internalization of the EGFR and EGFR-mediated signaling pathways.
C1 [Kim, Jong Hyun; Wang, Aibing; Conti, Mary Anne; Adelstein, Robert S.] NHLBI, Mol Cardiol Lab, NIH, Bethesda, MD 20892 USA.
RP Kim, JH (reprint author), Seoul Natl Univ, Med Bioconvergence Res Ctr, Seoul 151742, South Korea.
EM nr.kimjohn@gmail.com; adelster@mail.nih.gov
OI Adelstein, Robert/0000-0002-8683-2144
FU Division of Intramural Research, NHLBI, National Institutes of Health
FX This work was supported by the Division of Intramural Research, NHLBI,
National Institutes of Health.
NR 50
TC 12
Z9 13
U1 0
U2 4
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD AUG 10
PY 2012
VL 287
IS 33
BP 27345
EP 27358
DI 10.1074/jbc.M111.304824
PG 14
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 993FF
UT WOS:000307840700007
PM 22718763
ER
PT J
AU Masaoka, A
Gassman, NR
Kedar, PS
Prasad, R
Hou, EW
Horton, JK
Bustin, M
Wilson, SH
AF Masaoka, Aya
Gassman, Natalie R.
Kedar, Padmini S.
Prasad, Rajendra
Hou, Esther W.
Horton, Julie K.
Bustin, Michael
Wilson, Samuel H.
TI HMGN1 Protein Regulates Poly(ADP-ribose) Polymerase-1 (PARP-1)
Self-PARylation in Mouse Fibroblasts
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID BASE-EXCISION-REPAIR; OXIDATIVE DNA-DAMAGE; CHROMOSOMAL-PROTEINS;
MAMMALIAN-CELLS; CHROMATIN INTERACTIONS; NUCLEAR FUNCTIONS;
GLYCOSYLASE-II; LIGASE-III; BETA; EXPRESSION
AB In mammalian cells, the nucleosome-binding protein HMGN1 (high mobility group N1) affects the structure and function of chromatin and plays a role in repair of damaged DNA. HMGN1 affects the interaction of DNA repair factors with chromatin and their access to damaged DNA; however, not all of the repair factors affected have been identified. Here, we report that HMGN1 affects the self-poly(ADP-ribosyl)ation (i.e., PARylation) of poly(ADP-ribose) polymerase-1 (PARP-1), a multifunctional and abundant nuclear enzyme known to recognize DNA lesions and promote chromatin remodeling, DNA repair, and other nucleic acid transactions. The catalytic activity of PARP-1 is activated by DNA with a strand break, and this results in self-PARylation and PARylation of other chromatin proteins. Using cells obtained from Hmgn1(-/-) and Hmgn1(+/+) littermate mice, we find that in untreated cells, loss of HMGN1 protein reduces PARP-1 self-PARylation. A similar result was obtained after MMS treatment of these cells. In imaging experiments after low energy laser-induced DNA damage, less PARylation at lesion sites was observed in Hmgn1(-/-) than in Hmgn1(+/+) cells. The HMGN1 regulation of PARP-1 activity could be mediated by direct protein-protein interaction as HMGN1 and PARP-1 were found to interact in binding assays. Purified HMGN1 was able to stimulate self-PARylation of purified PARP-1, and in experiments with cell extracts, self-PARylation was greater in Hmgn1(+/+) than in Hmgn1(-/-) extract. The results suggest a regulatory role for HMGN1 in PARP-1 activation.
C1 [Masaoka, Aya; Gassman, Natalie R.; Kedar, Padmini S.; Prasad, Rajendra; Hou, Esther W.; Horton, Julie K.; Wilson, Samuel H.] NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA.
[Bustin, Michael] NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Wilson, SH (reprint author), NIEHS, Struct Biol Lab, NIH, 111 TW Alexander Dr,POB 12233,MD F1-12, Res Triangle Pk, NC 27709 USA.
EM wilson5@niehs.nih.gov
RI Bustin, Michael/G-6155-2015;
OI Gassman, Natalie/0000-0002-8488-2332
FU Intramural Research Program of the National Institutes of Health, NIEHS
[Z01-ES050158, Z01-ES050159]
FX This work was supported, in whole or in part, by Research Projects
Z01-ES050158 and Z01-ES050159 in the Intramural Research Program of the
National Institutes of Health, NIEHS.
NR 60
TC 12
Z9 13
U1 2
U2 6
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD AUG 10
PY 2012
VL 287
IS 33
BP 27648
EP 27658
DI 10.1074/jbc.M112.370759
PG 11
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 993FF
UT WOS:000307840700039
PM 22736760
ER
PT J
AU Boura, E
Ivanov, V
Carlson, LA
Mizuuchi, K
Hurley, JH
AF Boura, Evzen
Ivanov, Vassili
Carlson, Lars-Anders
Mizuuchi, Kiyoshi
Hurley, James H.
TI Endosomal Sorting Complex Required for Transport (ESCRT) Complexes
Induce Phase-separated Microdomains in Supported Lipid Bilayers
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID UBIQUITIN-BINDING DOMAINS; MULTIVESICULAR BODY BIOGENESIS;
PHOSPHATIDYLINOSITOL 4,5-BISPHOSPHATE; MOLECULAR-MECHANISM; EAP45-GLUE
DOMAIN; VESICLE FORMATION; STRUCTURAL BASIS; PLASMA-MEMBRANE; III
FILAMENTS; PROTEIN
AB The endosomal sorting complex required for transport (ESCRT) system traffics ubiquitinated cargo to lysosomes via an unusual membrane budding reaction that is directed away from the cytosol. Here, we show that human ESCRT-II self-assembles into clusters of 10-100 molecules on supported lipid bilayers. The ESCRT-II clusters are functional in that they bind to ubiquitin and the ESCRT-III subunit VPS20 at nanomolar concentrations on membranes with the same stoichiometries observed in solution and in crystals. The clusters only form when cholesterol is included in the lipid mixture at >10 mol %. The clusters induce the formation of ordered membrane domains that exclude the dye 1,1'-dioctadecyl-3,3,3',3'-tetramethylindodicarbo-cyanine perchlorate. These results show that ESCRT complexes are capable of inducing lateral lipid phase separation under conditions where the lipids themselves do not spontaneously phase-separate. This property could facilitate ESCRT-mediated membrane budding.
C1 [Boura, Evzen; Ivanov, Vassili; Carlson, Lars-Anders; Mizuuchi, Kiyoshi; Hurley, James H.] NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Hurley, JH (reprint author), NIDDK, Mol Biol Lab, NIH, Bldg 50,Rm 4517, Bethesda, MD 20892 USA.
EM james.hurley@nih.gov
RI Boura, Evzen/G-5275-2014
FU National Institutes of Health Intramural Program, NIDDK; Intramural AIDS
Targeted Anti-viral Program of the Office of the Director; Intramural
AIDS Research Fellowship; Human Frontier Science Program postdoctoral
fellowship
FX This work was supported, in whole or in part, by National Institutes of
Health Intramural Program, NIDDK (to K. M. and J. H. H.), and the
Intramural AIDS Targeted Anti-viral Program of the Office of the
Director (to J. H. H.).; Supported by an Intramural AIDS Research
Fellowship. Present address: Institute of Organic Chemistry and
Biochemistry of the Academy of Sciences of the Czech Republic,
Flemingovo nam. 2., 166 10 Praha 6, Czech Republic.; Supported by a
Human Frontier Science Program postdoctoral fellowship.
NR 47
TC 22
Z9 22
U1 0
U2 5
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD AUG 10
PY 2012
VL 287
IS 33
BP 28144
EP 28151
DI 10.1074/jbc.M112.378646
PG 8
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 993FF
UT WOS:000307840700087
PM 22718754
ER
PT J
AU Cheson, BD
Byrd, JC
Rai, KR
Kay, NE
O'Brien, SM
Flinn, IW
Wiestner, A
Kipps, TJ
AF Cheson, Bruce D.
Byrd, John C.
Rai, Kanti R.
Kay, Neil E.
O'Brien, Susan M.
Flinn, Ian W.
Wiestner, Adrian
Kipps, Thomas J.
TI Novel Targeted Agents and the Need to Refine Clinical End Points in
Chronic Lymphocytic Leukemia
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Editorial Material
ID SPONSORED-WORKING-GROUP; B-CELL RECEPTOR; RESPONSE CRITERIA; CLL CELLS;
PHASE-II; IN-VIVO; LYMPHOMA; LENALIDOMIDE; INHIBITOR; GUIDELINES
C1 [Cheson, Bruce D.] Georgetown Univ Hosp, Lombardi Comprehens Canc Ctr, Washington, DC 20007 USA.
[Byrd, John C.] Ohio State Univ, Columbus, OH 43210 USA.
[Rai, Kanti R.] Long Isl Jewish Med Ctr, New Hyde Pk, NY 11042 USA.
[Kay, Neil E.] Mayo Clin, Rochester, MN USA.
[O'Brien, Susan M.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Flinn, Ian W.] Sarah Cannon Res Inst, Nashville, TN USA.
[Wiestner, Adrian] NIH, Bethesda, MD 20892 USA.
[Kipps, Thomas J.] Univ Calif San Diego, Moores Canc Ctr, San Diego, CA 92103 USA.
RP Cheson, BD (reprint author), Georgetown Univ Hosp, Lombardi Comprehens Canc Ctr, Washington, DC 20007 USA.
FU NCI NIH HHS [P01 CA081534, P30 CA016058]
NR 20
TC 91
Z9 92
U1 0
U2 2
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD AUG 10
PY 2012
VL 30
IS 23
BP 2820
EP 2822
DI 10.1200/JCO.2012.43.3748
PG 3
WC Oncology
SC Oncology
GA 992KS
UT WOS:000307775000011
PM 22778323
ER
PT J
AU Forsythe, LP
Alfano, CM
Leach, CR
Ganz, PA
Stefanek, ME
Rowland, JH
AF Forsythe, Laura P.
Alfano, Catherine M.
Leach, Corinne R.
Ganz, Patricia A.
Stefanek, Michael E.
Rowland, Julia H.
TI Who Provides Psychosocial Follow-Up Care for Post-Treatment Cancer
Survivors? A Survey of Medical Oncologists and Primary Care Physicians
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID OUTCOMES RESEARCH; BREAST-CANCER; DEPRESSION; PATIENT; COMPLETION;
MORTALITY; PROSTATE; SMOKING; SUPPORT; WOMEN
AB Purpose
Addressing psychosocial needs, including key components of psychologic distress, physical symptoms, and health promotion, is vital to cancer follow-up care. Yet little is known about who provides psychosocial care. This study examined physician-reported practices regarding care of post-treatment cancer survivors. We sought to characterize physicians who reported broad involvement in (ie, across key components of care) and shared responsibility for psychosocial care.
Methods
A nationally representative sample of medical oncologists (n = 1,130) and primary care physicians (PCPs; n = 1,021) were surveyed regarding follow-up care of breast and colon cancer survivors.
Results
Approximately half of oncologists and PCPs (52%) reported broad involvement in psychosocial care. Oncologist and PCP confidence, beliefs about who is able to provide psychosocial support, and preferences for shared responsibility for care predicted broad involvement. However, oncologists' and PCPs' perceptions of who provides specific aspects of psychosocial care differed (P < .001); both groups saw themselves as the main providers. Oncologists' confidence, PCPs' beliefs about who is able to provide psychosocial support, and oncologist and PCP preference for models other than shared care were inversely associated with a shared approach to care.
Conclusion
Findings that some providers are not broadly involved in psychosocial care and that oncologists and PCPs differ in their beliefs regarding who provides specific aspects of care underscore the need for better care coordination, informed by the respective skills and desires of physicians, to ensure needs are met. Interventions targeting physician confidence, beliefs about who is able to provide psychosocial support, and preferred models for survivorship care may improve psychosocial care delivery.
C1 [Forsythe, Laura P.; Alfano, Catherine M.; Rowland, Julia H.] NCI, NIH, Bethesda, MD 20892 USA.
[Leach, Corinne R.] Amer Canc Soc, Atlanta, GA 30329 USA.
[Ganz, Patricia A.] Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA.
[Ganz, Patricia A.] Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA.
[Stefanek, Michael E.] Indiana Univ, Bloomington, IN USA.
RP Forsythe, LP (reprint author), 6116 Execut Blvd,Suite 404,MSC 8336, Rockville, MD 20892 USA.
EM laura.forsythe@nih.gov
FU National Cancer Institute [HHSN261200700068C]; American Cancer Society
Behavioral Research Center
FX Supported by Contract No. HHSN261200700068C from the National Cancer
Institute and by intramural research funds from the American Cancer
Society Behavioral Research Center.
NR 47
TC 27
Z9 28
U1 1
U2 13
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD AUG 10
PY 2012
VL 30
IS 23
BP 2897
EP 2905
DI 10.1200/JCO.2011.39.9832
PG 9
WC Oncology
SC Oncology
GA 992KS
UT WOS:000307775000022
PM 22778322
ER
PT J
AU Busaidy, NL
Farooki, A
Dowlati, A
Perentesis, JP
Dancey, JE
Doyle, LA
Brell, JM
Siu, LL
AF Busaidy, Naifa L.
Farooki, Azeez
Dowlati, Afshin
Perentesis, John P.
Dancey, Janet E.
Doyle, Laurence A.
Brell, Joanna M.
Siu, Lillian L.
TI Management of Metabolic Effects Associated With Anticancer Agents
Targeting the PI3K-Akt-mTOR Pathway
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID BLOOD-GLUCOSE CONTROL; RENAL-CELL CARCINOMA; PHASE-I TRIAL; MAMMALIAN
TARGET; ADVANCED MALIGNANCIES; DIABETES-MELLITUS; RAPAMYCIN; SIROLIMUS;
INHIBITION; RISK
AB Agents inhibiting the phosphoinositide 3-kinase-Akt-mammalian target of rapamycin (PAM) pathway are currently in various stages of clinical development in oncology, ranging from some in early-phase evaluations to others that have already received regulatory approval for treatment in advanced cancers. The administration of PAM pathway inhibitors has been associated with metabolic toxicities of hyperlipidemia and hyperglycemia. The PAM Task Force of the National Cancer Institute Investigational Drug Steering Committee convened an interdisciplinary expert panel to review the pathophysiology of hyperlipidemia and hyperglycemia induced by PAM pathway inhibitors, summarize the incidence of these metabolic toxicities induced by such agents in the current literature, advise on clinical trial screening and monitoring criteria, and provide management guidance and therapeutic goals on occurrence of these toxicities. The overarching aim of this consensus report is to raise awareness of these metabolic adverse events to enable their early recognition, regular monitoring, and timely intervention in clinical trials. Hyperglycemia and hyperlipidemia are generally not acutely toxic and most often reversible with therapeutic intervention. Dose modifications or discontinuation of PAM pathway inhibitors should only be considered in situations of severe events or if progressive metabolic derangement persists after therapeutic interventions have been attempted for a sufficient duration. Specialty consultation should be sought to aid clinical trial planning and the management of these metabolic adverse events.
C1 [Busaidy, Naifa L.] Univ Texas MD Anderson Canc Ctr, Dept Endocrine Neoplasia & Hormonal Disorders, Houston, TX 77030 USA.
[Farooki, Azeez] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
[Dowlati, Afshin] Case Western Reserve Univ, Cleveland, OH 44106 USA.
[Perentesis, John P.] Cincinnati Childrens Hosp, Cincinnati, OH USA.
[Dancey, Janet E.] Ontario Inst Canc Res, Toronto, ON, Canada.
[Siu, Lillian L.] Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada.
[Doyle, Laurence A.; Brell, Joanna M.] NCI, Bethesda, MD 20892 USA.
RP Busaidy, NL (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Endocrine Neoplasia & Hormonal Disorders, 1515 Holcombe Blvd, Houston, TX 77030 USA.
EM nbusaidy@mdanderson.org
FU National Cancer Institute Coordinating Center for Clinical Trials;
Genentech; GlaxoSmithKline; Merck; Novartis; Pfizer
FX Supported by the National Cancer Institute Coordinating Center for
Clinical Trials.; Research Funding: Lillian L. Siu, Genentech,
GlaxoSmithKline, Merck, Novartis, Pfizer
NR 38
TC 78
Z9 80
U1 1
U2 9
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD AUG 10
PY 2012
VL 30
IS 23
BP 2919
EP 2928
DI 10.1200/JCO.2011.39.7356
PG 10
WC Oncology
SC Oncology
GA 992KS
UT WOS:000307775000025
PM 22778315
ER
PT J
AU Hristova, VA
Stringer, DK
Weissman, AM
AF Hristova, Ventzislava A.
Stringer, Daniel K.
Weissman, Allan M.
TI Cullin RING Ligases: Glommed by Glomulin
SO MOLECULAR CELL
LA English
DT Editorial Material
ID UBIQUITIN LIGASES; TURNOVER
AB Cullin ring ligases (CRLs) constitute the largest group of RING finger ubiquitin ligases. Two recent studies in Molecular Cell describe glomulin as a CRL1 inhibitor that blocks interactions with its ubiquitin-conjugating enzyme (E2) (Duda et al., 2012; Tron et al., 2012). These findings and their significance are discussed.
C1 [Hristova, Ventzislava A.; Stringer, Daniel K.; Weissman, Allan M.] NCI, Lab Prot Dynam & Signaling, Ctr Canc Res, Frederick, MD 21702 USA.
RP Weissman, AM (reprint author), NCI, Lab Prot Dynam & Signaling, Ctr Canc Res, 1050 Boyles St, Frederick, MD 21702 USA.
EM weissmaa@mail.nih.gov
FU Intramural NIH HHS [ZIA BC010292-12]
NR 9
TC 0
Z9 0
U1 1
U2 2
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1097-2765
J9 MOL CELL
JI Mol. Cell
PD AUG 10
PY 2012
VL 47
IS 3
BP 331
EP 332
DI 10.1016/j.molcel.2012.07.025
PG 2
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 988IT
UT WOS:000307484600001
PM 22883621
ER
PT J
AU Baskaran, S
Ragusa, MJ
Boura, E
Hurley, JH
AF Baskaran, Sulochanadevi
Ragusa, Michael J.
Boura, Evzen
Hurley, James H.
TI Two-Site Recognition of Phosphatidylinositol 3-Phosphate by PROPPINs in
Autophagy
SO MOLECULAR CELL
LA English
DT Article
ID VACUOLE TARGETING PATHWAY; SACCHAROMYCES-CEREVISIAE; CRYSTAL-STRUCTURE;
PX DOMAIN; ENDOPLASMIC-RETICULUM; MONITORING AUTOPHAGY; BINDING-PROTEIN;
YEAST; COMPLEX; ATG21
AB Macroautophagy is essential to cell survival during starvation and proceeds by the growth of a double-membraned phagophore, which engulfs cytosol and other substrates. The synthesis and recognition of the lipid phosphatidylinositol 3-phosphate, PI(3)P, is essential for autophagy. The key autophagic PI(3)P sensors, which are conserved from yeast to humans, belong to the PROPPIN family. Here we report the crystal structure of the yeast PROPPIN Hsv2. The structure consists of a seven-bladed beta-propeller and, unexpectedly, contains two pseudo-equivalent PI(3)P binding sites on blades 5 and 6. These two sites both contribute to membrane binding in vitro and are collectively required for full autophagic function in yeast. These sites function in concert with membrane binding by a hydrophobic loop in blade 6, explaining the specificity of the PROPPINs for membrane-bound PI(3)P. These observations thus provide a structural and mechanistic framework for one of the conserved central molecular recognition events in autophagy.
C1 [Baskaran, Sulochanadevi; Ragusa, Michael J.; Boura, Evzen; Hurley, James H.] NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Hurley, JH (reprint author), NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
EM james.hurley@nih.gov
RI Boura, Evzen/I-2626-2012; Boura, Evzen/G-5275-2014
FU U.S. Department of Energy, Office of Science, Office of Basic Energy
Sciences [W-31-109-Eng-38]; NIH, NIDDK; Intramural AIDS Research
Fellowship; NASA [GM099319]
FX We thank D. Klionsky, R. Youle, W. Prinz, M. Lemmon, and L Weisman for
strains and DNA constructs; S. Harrison for suggesting K. lactis; B.
Canagarajah for assistance with figures; L. Saidi and B. Beach for
technical assistance; and R. Stanley for discussions. Crystallographic
data were collected at Southeast Regional Collaborative Access Team
22-ID beamline at the Advanced Photon Source, Argonne National
Laboratory. Use of the Advanced Photon Source was supported by the U.S.
Department of Energy, Office of Science, Office of Basic Energy
Sciences, under Contract No. W-31-109-Eng-38. This research was
supported by the Intramural Program of the NIH, NIDDK (J.H.H.), an
Intramural AIDS Research Fellowship (E.B.), and Ruth Kirschtein NASA
fellowship GM099319 (M.J.R.).
NR 45
TC 47
Z9 50
U1 1
U2 6
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1097-2765
J9 MOL CELL
JI Mol. Cell
PD AUG 10
PY 2012
VL 47
IS 3
BP 339
EP 348
DI 10.1016/j.molcel.2012.05.027
PG 10
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 988IT
UT WOS:000307484600004
PM 22704557
ER
PT J
AU Xu, WP
Mollapour, M
Prodromou, C
Wang, SQ
Scroggins, BT
Palchick, Z
Beebe, K
Siderius, M
Lee, MJ
Couvillon, A
Trepel, JB
Miyata, Y
Matts, R
Neckers, L
AF Xu, Wanping
Mollapour, Mehdi
Prodromou, Chrisostomos
Wang, Suiquan
Scroggins, Bradley T.
Palchick, Zach
Beebe, Kristin
Siderius, Marco
Lee, Min-Jung
Couvillon, Anthony
Trepel, Jane B.
Miyata, Yoshihiko
Matts, Robert
Neckers, Len
TI Dynamic Tyrosine Phosphorylation Modulates Cycling of the
HSP90-P50(CDC37)-AHA1 Chaperone Machine
SO MOLECULAR CELL
LA English
DT Article
ID C-TERMINAL DOMAIN; MOLECULAR CHAPERONE; PROTEIN-KINASES; ATPASE
ACTIVITY; HSP90; CDC37; ACTIVATION; BINDING; AHA1; SERINE-13
AB Many critical protein kinases rely on the Hsp90 chaperone machinery for stability and function. After initially forming a ternary complex with kinase client and the cochaperone p50(Cdc37), Hsp90 proceeds through a cycle of conformational changes facilitated by ATP binding and hydrolysis. Progression through the chaperone cycle requires release of p50(Cdc37) and recruitment of the ATPase activating cochaper-one AHA1, but the molecular regulation of this complex process at the cellular level is poorly understood. We demonstrate that a series of tyrosine phosphorylation events, involving both p50(Cdc37) and Hsp90, are minimally sufficient to provide directionality to the chaperone cycle. p50(Cdc37) phosphorylation on Y4 and Y298 disrupts client-p50(Cdc37) association, while Hsp90 phosphorylation on Y197 dissociates p50(Cdc37) from Hsp90. Hsp90 phosphorylation on Y313 promotes recruitment of AHA1, which stimulates Hsp90 ATPase activity, furthering the chaperoning process. Finally, at completion of the chaperone cycle, Hsp90 Y627 phosphorylation induces dissociation of the client and remaining cochaperones.
C1 [Xu, Wanping; Mollapour, Mehdi; Wang, Suiquan; Scroggins, Bradley T.; Palchick, Zach; Beebe, Kristin; Neckers, Len] NCI, Urol Oncol Branch, Bethesda, MD 20892 USA.
[Lee, Min-Jung; Trepel, Jane B.] NCI, Med Oncol Branch, Bethesda, MD 20892 USA.
[Prodromou, Chrisostomos] Univ Sussex, Genome Damage & Stabil Ctr, Brighton, E Sussex, England.
[Siderius, Marco] Vrije Univ Amsterdam, Fac Sci, Amsterdam, Netherlands.
[Couvillon, Anthony] Cell Signaling Technol, Growth & Viabil Sect, Cell Biol, Danvers, MA 01923 USA.
[Miyata, Yoshihiko] Kyoto Univ, Grad Sch Biostudies, Dept Cell & Dev Biol, Kyoto, Japan.
[Matts, Robert] Oklahoma State Univ, Dept Biochem & Mol Biol, Stillwater, OK 74078 USA.
RP Neckers, L (reprint author), NCI, Urol Oncol Branch, Bethesda, MD 20892 USA.
EM neckers@nih.gov
OI Prodromou, Chrisostomos/0000-0003-4320-1147
FU Intramural NIH HHS [Z01 SC010074-13, Z01 SC010074-12, Z99 CA999999, ZIA
BC011032-02, ZIA BC011032-03, ZIA BC011032-05, ZIA SC010074-14, ZIA
SC010074-15, ZIA SC010074-17]; NCI NIH HHS [Z01 BC011032-01]; Wellcome
Trust [095605]
NR 22
TC 46
Z9 46
U1 2
U2 11
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1097-2765
J9 MOL CELL
JI Mol. Cell
PD AUG 10
PY 2012
VL 47
IS 3
BP 434
EP 443
DI 10.1016/j.molcel.2012.05.015
PG 10
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 988IT
UT WOS:000307484600012
PM 22727666
ER
PT J
AU Klepac, P
Bjornstad, ON
Metcalf, CJE
Grenfell, BT
AF Klepac, Petra
Bjornstad, Ottar N.
Metcalf, C. Jessica E.
Grenfell, Bryan T.
TI Optimizing Reactive Responses to Outbreaks of Immunizing Infections:
Balancing Case Management and Vaccination
SO PLOS ONE
LA English
DT Article
ID MEASLES EPIDEMICS; EPIDEMIOLOGIC INTERVENTIONS; PATHOGEN TRANSMISSION;
SPATIAL HIERARCHIES; ADAPTIVE MANAGEMENT; DYNAMICS; DISEASE; TIME;
PERSISTENCE; INFLUENZA
AB For vaccine-preventable infections, immunization generally needs to be supplemented by palliative care of individuals missed by the vaccination. Costs and availability of vaccine doses and palliative care vary by disease and by region. In many situations, resources for delivery of palliative care are independent of resources required for vaccination; however we also need to consider the conservative scenario where there is some trade-off between efforts, which is of potential relevance for resource-poor settings. We formulate an SEIR model that includes those two control strategies - vaccination and palliative care. We consider their relative merit and optimal allocation in the context of a highly efficacious vaccine, and under the assumption that palliative care may reduce transmission. We investigate the utility of a range of mixed or pure strategies that can be implemented after an epidemic has started, and look for rule-of-thumb principles of how best to reduce the burden of disease during an acute outbreak over a spectrum of vaccine-preventable infections. Intuitively, we expect the best strategy to initially focus on vaccination, and enhanced palliative care after the infection has peaked, but a number of plausible realistic constraints for control result in important qualifications on the intervention strategy. The time in the epidemic when one should switch strategy depends sensitively on the relative cost of vaccine to palliative care, the available budget, and R-0. Crucially, outbreak response vaccination may be more effective in managing low-R-0 diseases, while high R-0 scenarios enhance the importance of routine vaccination and case management.
C1 [Klepac, Petra; Grenfell, Bryan T.] Princeton Univ, Dept Ecol & Evolutionary Biol, Princeton, NJ 08544 USA.
[Bjornstad, Ottar N.] Penn State Univ, Ctr Infect Dis Dynam, University Pk, PA 16802 USA.
[Bjornstad, Ottar N.; Grenfell, Bryan T.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Metcalf, C. Jessica E.] Univ Oxford, Dept Zool, Oxford OX1 3PS, England.
[Grenfell, Bryan T.] Princeton Univ, Woodrow Wilson Sch, Princeton, NJ 08544 USA.
RP Klepac, P (reprint author), Princeton Univ, Dept Ecol & Evolutionary Biol, Princeton, NJ 08544 USA.
EM pklepac@alum.mit.edu
RI Bjornstad, Ottar/I-4518-2012
FU Bill and Melinda Gates Foundation; RAPIDD program of the Science &
Technology Directorate, Department of Homeland Security; Fogarty
International Center, National Institutes of Health
FX This research was supported by the Bill and Melinda Gates Foundation,
the RAPIDD program of the Science & Technology Directorate, Department
of Homeland Security, and the Fogarty International Center, 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 53
TC 6
Z9 6
U1 0
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 10
PY 2012
VL 7
IS 8
AR e41428
DI 10.1371/journal.pone.0041428
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 986XO
UT WOS:000307380900011
PM 22899996
ER
PT J
AU Virnik, K
Ni, YS
Berkower, I
AF Virnik, Konstantin
Ni, Yisheng
Berkower, Ira
TI Live attenuated rubella viral vectors stably express HIV and SIV vaccine
antigens while reaching high titers
SO VACCINE
LA English
DT Article
DE Live viral vectors; Rubella vaccine strain RA27/3; Stable expression;
HIV MPER; SIV Gag; Vaccine antigen
ID IMMUNODEFICIENCY-VIRUS TYPE-1; EQUINE ENCEPHALITIS-VIRUS; PROXIMAL
EXTERNAL REGION; CLASS-I MOLECULE; HUMAN MONOCLONAL-ANTIBODY;
NONSTRUCTURAL PROTEIN; RHESUS MACAQUES; NEUTRALIZING ANTIBODY; NEF GENE;
REPLICATION
AB Live attenuated viruses make potent and effective vaccines. Despite the urgent need for an HIV vaccine, this approach has not been feasible, since it has not been possible to attenuate the virus reliably and guarantee vaccine safety. Instead, live viral vectors have been proposed that could present HIV vaccine antigens in the most immunogenic way, in the context of an active infection. We have adapted the rubella vaccine strain RA27/3 as a vector to express HIV and SIV antigens, and tested the effect of insert size and composition on vector stability and viral titer. We have identified an acceptor site in the rubella nonstructural gene region, where foreign genes can be expressed as a fusion protein with the non-structural protein P150 without affecting essential viral functions. The inserts were expressed as early genes of rubella, under control of the rubella genomic promoter. At this site, HIV and SIV antigens were expressed stably for at least seven passages, as the rubella vectors reached high titers. Rubella readily infects rhesus macaques, and these animals will provide an ideal model for testing the new vectors for replication in vivo, immunogenicity, and protection against SIV or SHIV challenge. Published by Elsevier Ltd.
C1 [Virnik, Konstantin; Ni, Yisheng; Berkower, Ira] US FDA, Immunoregulat Lab, Div Viral Prod, Off Vaccines,Ctr Biol, Bethesda, MD 20892 USA.
RP Berkower, I (reprint author), US FDA, Immunoregulat Lab, Div Viral Prod, Off Vaccines,Ctr Biol, Bldg 29,Room 523,NIH Campus, Bethesda, MD 20892 USA.
EM ira.berkower@fda.hhs.gov
FU Intramural NIH HHS [Z99 OD999999]
NR 49
TC 6
Z9 6
U1 0
U2 1
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0264-410X
J9 VACCINE
JI Vaccine
PD AUG 10
PY 2012
VL 30
IS 37
BP 5453
EP 5458
DI 10.1016/j.vaccine.2012.06.074
PG 6
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA 991JR
UT WOS:000307697800002
PM 22776214
ER
PT J
AU Hammond, GRV
Fischer, MJ
Anderson, KE
Holdich, J
Koteci, A
Balla, T
Irvine, RF
AF Hammond, Gerald R. V.
Fischer, Michael J.
Anderson, Karen E.
Holdich, Jon
Koteci, Ardita
Balla, Tamas
Irvine, Robin F.
TI PI4P and PI(4,5)P-2 Are Essential But Independent Lipid Determinants of
Membrane Identity
SO SCIENCE
LA English
DT Article
ID PHOSPHATIDYLINOSITOL 4,5-BISPHOSPHATE; PLASMA-MEMBRANE; LIVING CELLS; K+
CHANNEL; PHOSPHOINOSITIDES; DOMAINS; POOLS; ACTIVATION; PROTEINS;
MULTIPLE
AB The quantitatively minor phospholipid phosphatidylinositol (4,5)-bisphosphate [PI(4,5)P-2] fulfills many cellular functions in the plasma membrane (PM), whereas its synthetic precursor, phosphatidylinositol 4-phosphate (PI4P), has no assigned PM roles apart from PI(4,5)P-2 synthesis. We used a combination of pharmacological and chemical genetic approaches to probe the function of PM PI4P, most of which was not required for the synthesis or functions of PI(4,5)P-2. However, depletion of both lipids was required to prevent PM targeting of proteins that interact with acidic lipids or activation of the transient receptor potential vanilloid 1 cation channel. Therefore, PI4P contributes to the pool of polyanionic lipids that define plasma membrane identity and to some functions previously attributed specifically to PI(4,5)P-2, which may be fulfilled by a more general polyanionic lipid requirement.
C1 [Hammond, Gerald R. V.; Fischer, Michael J.; Holdich, Jon; Koteci, Ardita; Irvine, Robin F.] Univ Cambridge, Dept Pharmacol, Cambridge CB2 1PD, England.
[Anderson, Karen E.] Babraham Inst, Inositide Lab, Cambridge CB22 3AT, England.
[Hammond, Gerald R. V.; Balla, Tamas] NICHHD, Sect Mol Signal Transduct, Program Dev Neurosci, NIH, Bethesda, MD 20892 USA.
RP Hammond, GRV (reprint author), Univ Cambridge, Dept Pharmacol, Tennis Court Rd, Cambridge CB2 1PD, England.
EM gerald.hammond@nih.gov; rfi20@cam.ac.uk
RI Hammond, Gerald/A-5759-2016;
OI Hammond, Gerald/0000-0002-6660-3272; Balla, Tamas/0000-0002-9077-3335
FU Wellcome Trust; Isaac Newton Trust; Alexander von Humboldt Foundation;
UK Biotechnology and Biological Sciences Research Council; Dame Rosemary
Murray Scholarship; Intramural Research Program of the Eunice Kennedy
Shriver National Institute of Child Health and Human Development
(NICHD), NIH
FX We thank M. Lemmon, K. Moravcevic, D. Oliver, D. D. Saur, and L.
Stephens for helpful discussions and constructs. G. R. V. H. and R. F.
I. were supported by the Wellcome Trust and the Isaac Newton Trust,
M.J.F. by the Alexander von Humboldt Foundation and the Isaac Newton
Trust, K. E. A. by the UK Biotechnology and Biological Sciences Research
Council, A. K. by a Dame Rosemary Murray Scholarship, and T. B. by the
Intramural Research Program of the Eunice Kennedy Shriver National
Institute of Child Health and Human Development (NICHD), NIH. We thank
V. Schram of the NICHD Microscopy and Imaging Core for technical
assistance with fluorescence recovery after photobleaching experiments.
Constructs used in this work are available from www.addgene.com.
NR 29
TC 145
Z9 150
U1 4
U2 49
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 0036-8075
J9 SCIENCE
JI Science
PD AUG 10
PY 2012
VL 337
IS 6095
BP 727
EP 730
DI 10.1126/science.1222483
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 986PE
UT WOS:000307354500053
PM 22722250
ER
PT J
AU Ma, BY
Nussinov, R
AF Ma, Buyong
Nussinov, Ruth
TI Selective Molecular Recognition in Amyloid Growth and Transmission and
Cross-Species Barriers
SO JOURNAL OF MOLECULAR BIOLOGY
LA English
DT Review
DE beta-amyloid oligomers; amyloid fibril structures; Alzheimer's disease;
prion; conformational selection
ID CONFORMATIONAL SELECTION; ALZHEIMERS-DISEASE; A-BETA; FIBRIL FORMATION;
PROTEIN AGGREGATION; BINDING CASCADES; ENERGY LANDSCAPE; ENZYME
CATALYSIS; FOLDING FUNNELS; PRION STRAINS
AB Mutual conformational selection and population shift followed by minor induced-fit optimization is the key mechanism in biomolecular recognition, and monomers and small oligomers binding to amyloid seeds in fibril growth is a molecular recognition event. Here, we describe amyloid aggregation, preferred species, cross-species barriers and transmission within the broad framework of molecular recognition. Cross-seeding of amyloid species is governed by conformational selection of compatible (complementary) states. If the dominant conformations of two species are similar, they can cross-seed each other; on the other hand, if they are sufficiently different, they will grow into different fibrils, reflecting species barriers. Such a scenario has recently been observed for the tau protein, which has four repeats. While a construct consisting of repeats 1, 3 and 4 can serve as a seed for the entire four-repeat tau segment, the inverse does not hold. On the other hand, the tau protein repeats with the characteristic U-turn shape can cross-seed Alzheimer's amyloid beta and, similarly, the islet amyloid polypeptide. Within this framework, we suggest that the so-called "central dogma" of amyloid formation, where aggregation takes place through nonspecific backbone hydrogen bonding interactions, which are common to all peptides and proteins, is a simple reflection of the heterogeneous, polymorphic free-energy landscape of amyloid species. Here, we review available data and make some propositions addressing this key problem. In particular, we argue that recent theoretical and experimental observations support the key role of selective molecular recognition in amyloidosis and in determining cross-species barriers and transmission. (C) 2011 Elsevier Ltd. All rights reserved.
C1 [Ma, Buyong; Nussinov, Ruth] NCI, Basic Sci Program, SAIC Frederick Inc, Ctr Canc Res Nanobiol Program, Frederick, MD 21702 USA.
[Nussinov, Ruth] Tel Aviv Univ, Sackler Sch Med, Dept Human Genet & Mol Med, Sackler Inst Mol Med, IL-69978 Tel Aviv, Israel.
RP Ma, BY (reprint author), NCI, Basic Sci Program, SAIC Frederick Inc, Ctr Canc Res Nanobiol Program, Frederick, MD 21702 USA.
EM mabuyong@mail.nih.gov; ruthnu@helix.nih.gov
RI Ma, Buyong/F-9491-2011
OI Ma, Buyong/0000-0002-7383-719X
FU National Cancer Institute, National Institutes of Health
[HHSN261200800001E]; National Institutes of Health, National Cancer
Institute, Center for Cancer Research
FX This project has been funded in whole or in part with federal funds from
the National Cancer Institute, National Institutes of Health, under
contract number HHSN261200800001E. The content of this publication does
not necessarily reflect the views or policies of the Department of
Health and Human Services, nor does mention of trade names, commercial
products or organizations imply endorsement by the U.S. Government. This
research was supported (in part) by the Intramural Research Program of
the National Institutes of Health, National Cancer Institute, Center for
Cancer Research.
NR 106
TC 39
Z9 39
U1 0
U2 47
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0022-2836
J9 J MOL BIOL
JI J. Mol. Biol.
PD AUG 10
PY 2012
VL 421
IS 2-3
BP 172
EP 184
DI 10.1016/j.jmb.2011.11.023
PN 1
PG 13
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 980HW
UT WOS:000306885200004
PM 22119878
ER
PT J
AU Yang, S
Griffin, MDW
Binger, KJ
Schuck, P
Howlett, GJ
AF Yang, Shuo
Griffin, Michael D. W.
Binger, Katrina J.
Schuck, Peter
Howlett, Geoffrey J.
TI An Equilibrium Model for Linear and Closed-Loop Amyloid Fibril Formation
SO JOURNAL OF MOLECULAR BIOLOGY
LA English
DT Article
DE fluorescence detection; sedimentation velocity; isodesmic;
apolipoprotein C-II; amyloid subunits
ID APOLIPOPROTEIN-C-II; PROTEIN-MISFOLDING DISEASES; FLUORESCENCE
DETECTION; ALZHEIMERS-DISEASE; CROSS-LINKING; NUCLEATION; KINETICS;
MECHANISM; ULTRACENTRIFUGATION; MACROMOLECULES
AB Amyloid fibrils and their soluble oligomeric intermediates are implicated in several age-related diseases including Alzheimer's and Parkinson's diseases. The distribution of oligomers and fibrils is related to toxicity and is dependent on the pathways for fibril assembly, generally considered to occur via a slow nucleation step that precedes fibril elongation. Human apolipoprotein (apo) C-II forms amyloid fibrils via a reversible self-assembly process accompanied by closed-loop formation and fibril breaking and joining. Our fluorescence quenching and sedimentation velocity experiments with Alexa488-labeled apoC-II indicated a time-dependent subunit interchange for both linear and closed-loop fibrils, while dilution experiments using mature fibrils indicated a shift to smaller size distributions consistent with a reversible assembly pathway. To account for this behavior, we developed an equilibrium self-association model that describes the final size distributions of apoC-II fibrils formed at different starting concentrations. The model proposes a reversible isomerization of apoC-II monomer to form an active conformer that self-assembles into fibrils via an isodesmic self-association pathway coupled to fibril length-dependent closed-loop formation. The model adequately described fibril size distributions and the proportion of closed loops as a function of total apoC-II concentration over the concentration range 0.1-0.5 mg/ml. Extension of the model to include the rates of isomerization, self-association and fibril breaking and joining provided satisfactory global fits to kinetic data on fibril formation and changes in average fibril size at different apoC-II starting concentrations. The model provides a simple thermodynamic description of the processes governing the size distribution of apoC-H fibrils at equilibrium and the formation of discrete oligomeric intermediates. (C) 2012 Elsevier Ltd. All rights reserved.
C1 [Yang, Shuo; Griffin, Michael D. W.; Binger, Katrina J.; Howlett, Geoffrey J.] Univ Melbourne, Dept Biochem & Mol Biol, Mol Sci & Biotechnol Inst Bio21, Melbourne, Vic 3010, Australia.
[Schuck, Peter] Natl Inst Biomed Imaging & Bioengn, Dynam Macromol Assembly Sect, Lab Cellular Imaging & Macromol Biophys, NIH, Bethesda, MD 20892 USA.
RP Howlett, GJ (reprint author), Univ Melbourne, Dept Biochem & Mol Biol, Mol Sci & Biotechnol Inst Bio21, Melbourne, Vic 3010, Australia.
EM ghowlett@unimelb.edu.au
OI Binger, Katrina/0000-0003-1139-3308; Schuck, Peter/0000-0002-8859-6966;
/0000-0001-9845-7735
FU Australian Research Council [DP0984565, DP110103528]; National Institute
of Biomedical Imaging and Bioengineering, National Institutes of Health
FX This research was supported under the Australian Research Council's
Discovery Projects funding scheme (project number DP0984565). M.D.W.G.
is the recipient of an Australian Research Council Post Doctoral
Fellowship (project number DP110103528). This work was supported in part
by the Intramural Research Program of the National Institute of
Biomedical Imaging and Bioengineering, National Institutes of Health.
NR 46
TC 11
Z9 11
U1 1
U2 18
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0022-2836
J9 J MOL BIOL
JI J. Mol. Biol.
PD AUG 10
PY 2012
VL 421
IS 2-3
BP 364
EP 377
DI 10.1016/j.jmb.2012.02.026
PN 1
PG 14
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 980HW
UT WOS:000306885200016
PM 22370559
ER
PT J
AU Minton, AP
AF Minton, Allen P.
TI Hard Quasispherical Particle Models for the Viscosity of Solutions of
Protein Mixtures
SO JOURNAL OF PHYSICAL CHEMISTRY B
LA English
DT Article
ID CONCENTRATED MONOCLONAL-ANTIBODY; REVERSIBLE SELF-ASSOCIATION; MAXIMUM
PACKING FRACTION; BOVINE SERUM-ALBUMIN; PHYSIOLOGICAL CONSEQUENCES;
BIDISPERSE SUSPENSIONS; SUSPENDED PARTICLES; GENERALIZED-MODEL; MYELOMA
PROTEIN; SPHERES
AB Recently reported measurements of the viscosity of three monoclonal antibodies, their binary mixtures, and a binary mixture of an antibody and albumin over a broad range of compositions (Galush et al., J. Pharm. Sci. 2011, 101, 1012) were quantitatively accounted for to within experimental uncertainty by an extension of the hard quasispherical particle model suggested by Ross and Minton (Biochem. Biophys. Res. Commun. 1977, 76, 971) and by a generalization of the hard sphere equation of Krieger and Dougherty (Trans. Soc. Rheol. 1959, 3, 137). Further generalization of these equations to treat the concentration-dependent viscosity of self-associating proteins is suggested.
C1 NIDDKD, Sect Phys Biochem, Lab Biochem & Genet, NIH,US Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
RP Minton, AP (reprint author), NIDDKD, Sect Phys Biochem, Lab Biochem & Genet, NIH,US Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
EM minton@helix.nih.gov
OI Minton, Allen/0000-0001-8459-1247
FU Intramural Research Program of the National Institute of Diabetes and
Digestive and Kidney Diseases, National Institutes of Health
FX The author thanks Dr. Peter McPhie (NIH) and Dr. William Galush
(Genentech) for reviewing and providing useful comments on the initial
draft of this report. Research of the author is supported by the
Intramural Research Program of the National Institute of Diabetes and
Digestive and Kidney Diseases, National Institutes of Health.
NR 37
TC 7
Z9 7
U1 0
U2 17
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 9
PY 2012
VL 116
IS 31
BP 9310
EP 9315
DI 10.1021/jp302748k
PG 6
WC Chemistry, Physical
SC Chemistry
GA 985KV
UT WOS:000307264400003
PM 22780089
ER
PT J
AU Scheinberg, P
Young, NS
AF Scheinberg, Phillip
Young, Neal S.
TI How I treat acquired aplastic anemia
SO BLOOD
LA English
DT Review
ID STEM-CELL TRANSPLANTATION; COLONY-STIMULATING FACTOR; ANTI-THYMOCYTE
GLOBULIN; BONE-MARROW FAILURE; HIGH-DOSE CYCLOPHOSPHAMIDE; RABBIT
ANTITHYMOCYTE GLOBULIN; CORD BLOOD TRANSPLANTATION; TOTAL-BODY
IRRADIATION; UNRELATED DONOR TRANSPLANTATION; SINGLE-CENTER EXPERIENCE
AB Survival in severe aplastic anemia (SAA) has markedly improved in the past 4 decades because of advances in hematopoietic stem cell transplantation, immunosuppressive biologics and drugs, and supportive care. However, management of SAA patients remains challenging, both acutely in addressing the immediate con-sequences of pancytopenia and in the long term because of the disease's natural history and the consequences of therapy. Recent insights into pathophysiology have practical implications. We review key aspects of differential diagnosis, considerations in the choice of first- and second-line therapies, and the management of patients after immunosuppression, based on both a critical review of the recent literature and our large personal and research protocol experience of bone marrow failure in the Hematology Branch of the National Heart, Lung, and Blood Institute. (Blood. 2012;120(6):1185-1196)
C1 [Scheinberg, Phillip; Young, Neal S.] NHLBI, Hematol Branch, Bethesda, MD 20892 USA.
RP Scheinberg, P (reprint author), NHLBI, Hematol Branch, 10 Ctr Dr,Bldg 10 CRC,Rm 3E-5140,MSC 1202, Bethesda, MD 20892 USA.
EM scheinbp@mail.nih.gov
OI Scheinberg, Phillip/0000-0002-9047-4538
FU Intramural Research Program of the NIH National Heart, Lung, and Blood
Institute
FX This work was supported by the Intramural Research Program of the NIH
National Heart, Lung, and Blood Institute.
NR 119
TC 117
Z9 140
U1 2
U2 26
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD AUG 9
PY 2012
VL 120
IS 6
BP 1185
EP 1196
DI 10.1182/blood-2011-12-274019
PG 12
WC Hematology
SC Hematology
GA 987WT
UT WOS:000307449300008
PM 22517900
ER
PT J
AU Hosszu, KK
Valentino, A
Vinayagasundaram, U
Vinayagasundaram, R
Joyce, MG
Ji, Y
Peerschke, EIB
Ghebrehiwet, B
AF Hosszu, Kinga K.
Valentino, Alisa
Vinayagasundaram, Uma
Vinayagasundaram, Rama
Joyce, M. Gordon
Ji, Yan
Peerschke, Ellinor I. B.
Ghebrehiwet, Berhane
TI DC-SIGN, C1q, and gC1qR form a trimolecular receptor complex on the
surface of monocyte-derived immature dendritic cells
SO BLOOD
LA English
DT Article
ID T-CELLS; PROTEIN; CALRETICULIN; ADHESION; SUBCOMPONENT; EXPRESSION;
MATURATION; MOLECULES; CLQ; IDENTIFICATION
AB C1q modulates the differentiation and function of cells committed to the monocyte-derived dendritic cell (DC) lineage. Because the 2 C1q receptors found on the DC surface-gC1qR and cC1qR-lack a direct conduit into intracellular elements, we postulated that the receptors must form complexes with transmembrane partners. In the present study, we show that DC-SIGN, a C-type lectin expressed on DCs, binds directly to C1q, as assessed by ELISA, flow cytometry, and immunoprecipitation experiments. Surface plasmon resonance analysis revealed that the interaction was specific, and both intact C1q and the globular portion of C1q bound to DC-SIGN. Whereas IgG reduced this binding significantly, the Arg residues (162-163) of the C1q-A chain, which are thought to contribute to the C1q-IgG interaction, were not required for C1q binding to DC-SIGN. Binding was reduced significantly in the absence of Ca2+ and by preincubation of DC-SIGN with mannan, suggesting that C1q binds to DC-SIGN at its principal Ca2+-binding pocket, which has increased affinity for mannose residues. Antigen-capture ELISA and immunofluorescence microscopy revealed that C1q and gC1qR associate with DC-SIGN on blood DC precursors and immature DCs. The results of the present study suggest that C1q/gC1qR may regulate DC differentiation and function through the DC-SIGN-mediated induction of cell-signaling pathways. (Blood. 2012;120(6):1228-1236)
C1 [Ghebrehiwet, Berhane] SUNY Stony Brook, Sch Med, Hlth Sci Ctr, Dept Med, Stony Brook, NY 11794 USA.
[Joyce, M. Gordon] NIAID, Struct Immunol Sect, Immunogenet Lab, NIH, Rockville, MD USA.
[Peerschke, Ellinor I. B.] Mt Sinai Sch Med, Dept Pathol, New York, NY USA.
RP Ghebrehiwet, B (reprint author), SUNY Stony Brook, Sch Med, Hlth Sci Ctr, Dept Med, T-16,Rm 040, Stony Brook, NY 11794 USA.
EM berhane.ghebrehiwet@stonybrook.edu
OI Hosszu, Kinga/0000-0002-1190-1491
FU National Institutes of Health [R01 AI 060866, R01 AI 084178]
FX This work was supported in part by grants from the National Institutes
of Health (R01 AI 060866 and R01 AI 084178).
NR 47
TC 18
Z9 21
U1 0
U2 8
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD AUG 9
PY 2012
VL 120
IS 6
BP 1228
EP 1236
DI 10.1182/blood-2011-07-369728
PG 9
WC Hematology
SC Hematology
GA 987WT
UT WOS:000307449300013
PM 22700724
ER
PT J
AU Yavlovich, A
Viard, M
Zhou, M
Veenstra, TD
Wang, JM
Gong, WH
Heldman, E
Blumenthal, R
Raviv, Y
AF Yavlovich, Amichai
Viard, Mathias
Zhou, Ming
Veenstra, Timothy D.
Wang, Ji Ming
Gong, Wanghua
Heldman, Eliahu
Blumenthal, Robert
Raviv, Yossef
TI Ectopic ATP synthase facilitates transfer of HIV-1 from
antigen-presenting cells to CD4(+) target cells
SO BLOOD
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; CELLULAR-PROTEINS; DC-SIGN; VIROLOGICAL
SYNAPSES; DENDRITIC CELLS; RECEPTOR; BINDING; SURFACE; TRANSMISSION;
HEPATOCYTES
AB Antigen-presenting cells (APCs) act as vehicles that transfer HIV to their target CD4(+) cells through an intercellular junction, termed the virologic synapse. The molecules that are involved in this process remain largely unidentified. In this study, we used photoaffinity labeling and a proteomic approach to identify new proteins that facilitate HIV-1 transfer. We identified ectopic mitochondrial ATP synthase as a factor that mediates HIV-1 transfer between APCs and CD4(+) target cells. Monoclonal antibodies against the beta-subunit of ATP synthase inhibited APC-mediated transfer of multiple strains HIV-1 to CD4(+) target cells. Likewise, the specific inhibitors of ATPase, citreoviridin and IF1, completely blocked APC-mediated transfer of HIV-1 at the APC-target cell interaction step. Confocal fluorescent microscopy showed localization of extracellular ATP synthase at junctions between APC and CD4(+) target cells. We conclude that ectopic ATP synthase could be an accessible molecular target for inhibiting HIV-1 proliferation in vivo. (Blood. 2012;120(6):1246-1253)
C1 [Yavlovich, Amichai; Viard, Mathias; Heldman, Eliahu; Blumenthal, Robert; Raviv, Yossef] Ctr Canc Res, Membrane Struct & Funct Sect, Nanobiol Program, Bethesda, MD USA.
[Viard, Mathias; Gong, Wanghua; Heldman, Eliahu; Raviv, Yossef] NCI, Basic Res Program SAIC Frederick, Frederick, MD 21701 USA.
[Zhou, Ming; Veenstra, Timothy D.] NCI, Lab Prote & Analyt Technol, Adv Technol Program, SAIC Frederick, Frederick, MD 21701 USA.
[Wang, Ji Ming; Gong, Wanghua] Ctr Canc Res, Mol Immunoregulat Lab, Canc & Inflammat Program, Bethesda, MD USA.
RP Raviv, Y (reprint author), Frederick Natl Lab Canc Res, Bldg 469,Room 213,POB B, Frederick, MD 21702 USA.
EM ravivy@mail.nih.gov
FU Frederick National Laboratory for Cancer Research; National Institutes
of Health [HHSN26120080001E]; Intramural AIDS Targeted Antiviral Program
FX This work was supported in whole or in part by the Frederick National
Laboratory for Cancer Research, Intramural Research Program of the
National Institutes of Health (contract HHSN26120080001E) and the
Intramural AIDS Targeted Antiviral Program.
NR 36
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Z9 8
U1 3
U2 4
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD AUG 9
PY 2012
VL 120
IS 6
BP 1246
EP 1253
DI 10.1182/blood-2011-12-399063
PG 8
WC Hematology
SC Hematology
GA 987WT
UT WOS:000307449300015
PM 22753871
ER
PT J
AU Baba, M
Keller, JR
Sun, HW
Resch, W
Kuchen, S
Suh, HC
Hasumi, H
Hasumi, Y
Kieffer-Kwon, KR
Gonzalez, CG
Hughes, RM
Klein, ME
Oh, HF
Bible, P
Southon, E
Tessarollo, L
Schmidt, LS
Linehan, WM
Casellas, R
AF Baba, Masaya
Keller, Jonathan R.
Sun, Hong-Wei
Resch, Wolfgang
Kuchen, Stefan
Suh, Hyung Chan
Hasumi, Hisashi
Hasumi, Yukiko
Kieffer-Kwon, Kyong-Rim
Gallego Gonzalez, Carme
Hughes, Robert M.
Klein, Mara E.
Oh, Hyoungbin F.
Bible, Paul
Southon, Eileen
Tessarollo, Lino
Schmidt, Laura S.
Linehan, W. Marston
Casellas, Rafael
TI The folliculin-FNIP1 pathway deleted in human Birt-Hogg-Dube syndrome is
required for murine B-cell development
SO BLOOD
LA English
DT Article
ID TRANSGENIC MICE; MTOR ACTIVATION; GENE-PRODUCT; MOUSE MODEL; BHD;
PROTEIN; TRANSCRIPTION; INACTIVATION; EXPRESSION; MUTATIONS
AB Birt-Hogg-Dube (BHD) syndrome is an autosomal dominant disorder characterized by cutaneous fibrofolliculomas, pulmonary cysts, and kidney malignancies. Affected individuals carry germ line mutations in folliculin (FLCN), a tumor suppressor gene that becomes biallelically inactivated in kidney tumors by second-hit mutations. Similar to other factors implicated in kidney cancer, FLCN has been shown to modulate activation of mammalian target of rapamycin (mTOR). However, its precise in vivo function is largely unknown because germ line deletion of Flcn results in early embryonic lethality in animal models. Here, we describe mice deficient in the newly characterized folliculin-interacting protein 1 (Fnip1). In contrast to Flcn, Fnip1(-/-) mice develop normally, are not susceptible to kidney neoplasia, but display a striking pro-B cell block that is entirely independent of mTOR activity. We show that this developmental arrest results from rapid caspase-induced pre-B cell death, and that a Bcl2 transgene reconstitutes mature B-cell populations, respectively. We also demonstrate that conditional deletion of Flcn recapitulates the pro-B cell arrest of Fnip1(-/-) mice. Our studies thus demonstrate that the FLCN-FNIP complex de-regulated in BHD syndrome is absolutely required for B-cell differentiation, and that it functions through both mTOR-dependent and independent pathways. (Blood.2012;120(6):1254-1261)
C1 [Resch, Wolfgang; Kuchen, Stefan; Kieffer-Kwon, Kyong-Rim; Casellas, Rafael] NCI, NIAMS, NIH, Bethesda, MD 20892 USA.
[Baba, Masaya; Hasumi, Hisashi; Hasumi, Yukiko; Hughes, Robert M.; Klein, Mara E.; Oh, Hyoungbin F.; Schmidt, Laura S.; Linehan, W. Marston] NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA.
[Keller, Jonathan R.; Suh, Hyung Chan] NCI, Lab Canc Prevent, NIH, Frederick, MD 21701 USA.
[Sun, Hong-Wei; Bible, Paul] Natl Inst Arthrit & Musculoskeletal & Skin Dis, Biodata Min & Discovery Sect, NIH, Bethesda, MD USA.
[Gallego Gonzalez, Carme] Inst Biol Mol Barcelona, Barcelona, Spain.
[Southon, Eileen; Schmidt, Laura S.] NCI Frederick, Basic Sci Program, SAIC Frederick, Frederick, MD USA.
[Tessarollo, Lino] NCI Frederick, Mouse Canc Genet Program, Ctr Canc, Frederick, MD USA.
[Casellas, Rafael] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Casellas, R (reprint author), NCI, NIAMS, NIH, 10 Ctr Dr,MSC 1930,10-13C103-D, Bethesda, MD 20892 USA.
EM wml@nih.gov; rafael.casellas@nih.gov
RI Baba, Masaya/L-7490-2013; Gallego, Carme/K-6573-2014;
OI Baba, Masaya/0000-0002-5308-6683; Kuchen, Stefan/0000-0003-4899-8132
FU NIAMS; NCI, Center for Cancer Research, National Institutes of Health
(NIH); NCI, NIH [HHSN261200800001E]
FX This work was supported in part by the Intramural Research Program of
NIAMS and NCI, Center for Cancer Research, National Institutes of Health
(NIH). This project was funded in part with federal funds from the NCI,
NIH, under contract no. HHSN261200800001E.
NR 26
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U1 0
U2 2
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD AUG 9
PY 2012
VL 120
IS 6
BP 1254
EP 1261
DI 10.1182/blood-2012-02-410407
PG 8
WC Hematology
SC Hematology
GA 987WT
UT WOS:000307449300016
PM 22709692
ER
PT J
AU Newman, AH
Beuming, T
Banala, AK
Donthamsett, P
Pongetti, K
LaBounty, A
Levy, B
Cao, JJ
Michino, M
Luedtke, RR
Javitch, JA
Shi, L
AF Newman, Amy Hauck
Beuming, Thijs
Banala, Ashwini K.
Donthamsett, Prashant
Pongetti, Katherine
LaBounty, Alex
Levy, Benjamin
Cao, Jianjing
Michino, Mayako
Luedtke, Robert R.
Javitch, Jonathan A.
Shi, Lei
TI Molecular Determinants of Selectivity and Efficacy at the Dopamine D3
Receptor
SO JOURNAL OF MEDICINAL CHEMISTRY
LA English
DT Article
ID FUNCTIONALIZED LINKING CHAINS; PROTEIN-COUPLED RECEPTORS;
CRYSTAL-STRUCTURE; ADRENERGIC-RECEPTOR; LIGAND-BINDING; D-3;
ANTAGONISTS; AFFINITY; ANALOGS; SITE
AB The dopamine D3 receptor (D3R) has been implicated in substance abuse and other neuropsychiatric disorders. The high sequence homology between the D3R and D2R, especially within the orthosteric binding site (OBS) that binds dopamine, has made the development of D3R-selective compounds challenging. Here, we deconstruct into pharmacophoric elements a series of D3R-selective substituted-4-phenylpiperazine compounds and use computational simulations and binding and activation studies to dissect the structural bases for D3R selectivity and efficacy. We find that selectivity arises from divergent interactions within a second binding pocket (SBP) separate from the OBS, whereas efficacy depends on the binding mode in the OBS. Our findings reveal structural features of the receptor that are critical to selectivity and efficacy that can be used to design highly D3R-selective ligands with targeted efficacies. These findings are generalizable to other GPCRs in which the SBP can be targeted by bitopic or allosteric ligands.
C1 [Newman, Amy Hauck; Banala, Ashwini K.; Levy, Benjamin; Cao, Jianjing] Natl Inst Drug Abuse, Med Chem Sect, Mol Targets & Medicat Discovery Branch, Intramural Res Program, Baltimore, MD USA.
[Beuming, Thijs] Schrodinger Inc, New York, NY USA.
[Donthamsett, Prashant; Javitch, Jonathan A.] Columbia Univ Coll Phys & Surg, Ctr Mol Recognit, New York, NY 10032 USA.
[Donthamsett, Prashant; Javitch, Jonathan A.] Columbia Univ Coll Phys & Surg, Dept Psychiat, New York, NY 10032 USA.
[Donthamsett, Prashant; Javitch, Jonathan A.] Columbia Univ Coll Phys & Surg, Dept Pharmacol, New York, NY 10032 USA.
[Pongetti, Katherine; LaBounty, Alex; Luedtke, Robert R.] Univ N Texas, Hlth Sci Ctr, Dept Pharmacol & Neurosci, Ft Worth, TX USA.
[Michino, Mayako; Shi, Lei] Cornell Univ, Dept Physiol & Biophys, New York, NY 10021 USA.
[Shi, Lei] Cornell Univ, Weill Med Coll, Inst Computat Biomed, New York, NY 10021 USA.
RP Newman, AH (reprint author), Natl Inst Drug Abuse, Med Chem Sect, Mol Targets & Medicat Discovery Branch, Intramural Res Program, Baltimore, MD USA.
EM anewman@intra.nida.nih.gov; jaj2@columbia.edu; les2007@med.cornell.edu
FU NIDA [DA022413, MH54137, DA23957, DA13584, DA023694]
FX We are grateful to R. Abel, W. Sherman, D. Lupyan, C. Gales, and R.
Stevens for helpful discussion, and R. Mach for the precursor used for
the iodination of [125I]IABN. This work was supported in part
by NIDA Intramural Research Program (A.H.N.), DA022413 and MH54137
(J.A.J.) DA23957 and DA13584 (R.R.L.), and DA023694 (L.S.). Computations
were performed on the Ranger at the Texas Advanced Computing Center
(TG-MCB090022).
NR 47
TC 60
Z9 60
U1 1
U2 21
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0022-2623
J9 J MED CHEM
JI J. Med. Chem.
PD AUG 9
PY 2012
VL 55
IS 15
BP 6689
EP 6699
DI 10.1021/jm300482h
PG 11
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA 985KS
UT WOS:000307264100004
PM 22632094
ER
PT J
AU Lowenthal, J
Hull, SC
Pearson, SD
AF Lowenthal, Justin
Hull, Sara Chandros
Pearson, Steven D.
TI The Ethics of Early Evidence - Preparing for a Possible Breakthrough in
Alzheimer's Disease
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Editorial Material
C1 [Lowenthal, Justin; Hull, Sara Chandros; Pearson, Steven D.] NIH, Dept Bioeth, Ctr Clin, Bethesda, MD 20892 USA.
[Hull, Sara Chandros] NHGRI, NIH, Off Clin Director, Bethesda, MD 20892 USA.
[Pearson, Steven D.] Massachusetts Gen Hosp, Inst Clin & Econ Review, Inst Technol Assessment, Boston, MA 02114 USA.
RP Lowenthal, J (reprint author), NIH, Dept Bioeth, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA.
RI Lowenthal, Justin/H-3728-2013;
OI Lowenthal, Justin/0000-0001-5909-0520
FU Intramural NIH HHS [Z99 HG999999]
NR 5
TC 12
Z9 12
U1 0
U2 6
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD AUG 9
PY 2012
VL 367
IS 6
BP 488
EP 490
DI 10.1056/NEJMp1203104
PG 4
WC Medicine, General & Internal
SC General & Internal Medicine
GA 986AE
UT WOS:000307310800002
PM 22873528
ER
PT J
AU Saloustros, E
Stratakis, CA
AF Saloustros, Emmanouil
Stratakis, Constantine A.
TI Coffee Drinking and Mortality
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Letter
ID CANCER; RISK
C1 [Saloustros, Emmanouil; Stratakis, Constantine A.] NIH, Bethesda, MD 20892 USA.
RP Saloustros, E (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA.
EM esaloustros@yahoo.gr
OI Saloustros, Emmanouil /0000-0002-0485-0120
NR 4
TC 0
Z9 0
U1 1
U2 1
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 9
PY 2012
VL 367
IS 6
BP 575
EP 576
PG 3
WC Medicine, General & Internal
SC General & Internal Medicine
GA 986AE
UT WOS:000307310800020
PM 22873545
ER
PT J
AU Freedman, ND
Park, Y
Sinha, R
AF Freedman, Neal D.
Park, Yikyung
Sinha, Rashmi
TI Coffee Drinking and Mortality REPLY
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Letter
C1 [Freedman, Neal D.; Park, Yikyung; Sinha, Rashmi] NCI, Rockville, MD USA.
RP Freedman, ND (reprint author), NCI, Rockville, MD USA.
EM freedmanne@mail.nih.gov
RI Sinha, Rashmi/G-7446-2015; Freedman, Neal/B-9741-2015
OI Sinha, Rashmi/0000-0002-2466-7462; Freedman, Neal/0000-0003-0074-1098
NR 5
TC 0
Z9 0
U1 0
U2 1
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 9
PY 2012
VL 367
IS 6
BP 576
EP 577
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA 986AE
UT WOS:000307310800022
ER
PT J
AU Karami, S
Colt, JS
Schwartz, K
Davis, FG
Ruterbusch, JJ
Munuo, SS
Wacholder, S
Stewart, PA
Graubard, BI
Rothman, N
Chow, WH
Purdue, MP
AF Karami, Sara
Colt, Joanne S.
Schwartz, Kendra
Davis, Faith G.
Ruterbusch, Julie J.
Munuo, Stella S.
Wacholder, Sholom
Stewart, Patricia A.
Graubard, Barry I.
Rothman, Nathanial
Chow, Wong-Ho
Purdue, Mark P.
TI A case-control study of occupation/industry and renal cell carcinoma
risk
SO BMC CANCER
LA English
DT Article
DE Kidney cancer; Renal cancer; Clear cell RCC; Occupation; Industry; Race
ID OCCUPATIONAL RISK; TRICHLOROETHYLENE EXPOSURE; AGRICULTURAL HEALTH;
CANCER-MORTALITY; STATES; HYPERTENSION; MUTATIONS; FARMERS; KIDNEY
AB Background: The role of occupation in the etiology of renal cell carcinoma (RCC) is unclear. Here, we investigated associations between employment in specific occupations and industries and RCC, and its most common histologic subtype, clear cell RCC (ccRCC).
Methods: Between 2002 and 2007, a population-based case-control study of Caucasians and African Americans (1,217 cases; 1,235 controls) was conducted within the Detroit and Chicago metropolitan areas to investigate risk factors for RCC. As part of this study, occupational histories were ascertained through in-person interviews. We computed odds ratios (ORs) and 95% confidence intervals (CIs) relating occupation and industry to RCC risk using adjusted unconditional logistic regression models.
Results: Employment in the agricultural crop production industry for five years or more was associated with RCC (OR = 3.3 [95% CI = 1.0-11.5]) and ccRCC in particular (OR = 6.3 [95% CI = 1.7-23.3], P for trend with duration of employment = 0.0050). Similarly, RCC risk was elevated for employment of five years or longer in non-managerial agricultural and related occupations (ORRCC = 2.1 [95% CI = 1.0-4.5]; ORccRCC = 3.1 [95% CI = 1.4-6.8]). Employment in the dry-cleaning industry was also associated with elevated risk (ORRCC = 2.0 [95% CI = 0.9-4.4], P for trend = 0.093; ORccRCC = 3.0 [95% CI = 1.2-7.4], P for trend = 0.031). Suggestive elevated associations were observed for police/public safety workers, health care workers and technicians, and employment in the electronics, auto repair, and cleaning/janitorial services industries; protective associations were suggested for many white-collar jobs including computer science and administrative occupations as well employment in the business, legislative, and education industries.
Conclusions: Our findings provide support for an elevated risk of RCC in the agricultural and dry-cleaning industries and suggest that these associations may be stronger for the ccRCC subtype. Additional studies are needed to confirm these findings.
C1 [Karami, Sara; Colt, Joanne S.; Wacholder, Sholom; Stewart, Patricia A.; Graubard, Barry I.; Rothman, Nathanial; Chow, Wong-Ho; Purdue, Mark P.] NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20892 USA.
[Schwartz, Kendra; Ruterbusch, Julie J.] Wayne State Univ, Karmanos Canc Inst, Detroit, MI 48201 USA.
[Davis, Faith G.] Univ Illinois, Chicago, IL 60612 USA.
[Munuo, Stella S.] Informat Management Serv Inc, Rockville, MD 20852 USA.
[Stewart, Patricia A.] Stewart Exposure Assessments LLC, Arlington, VA USA.
RP Karami, S (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, DHHS, 6120 Execut Blvd,MSC 7242, Bethesda, MD 20892 USA.
EM karamis@mail.nih.gov
RI Purdue, Mark/C-9228-2016
OI Purdue, Mark/0000-0003-1177-3108
FU National Institutes of Health; National Cancer Institute [NO2-CP-10128,
N02-CP-11004, N02-CP-11161]
FX This study was supported by the Intramural Research Program of the
National Institutes of Health and the National Cancer Institute with
contracts NO2-CP-10128 (Westat, Inc.), N02-CP-11004 (Wayne State
University), and N02-CP-11161 (University of Illinois at Chicago).
NR 48
TC 4
Z9 4
U1 1
U2 19
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 8
PY 2012
VL 12
AR 344
DI 10.1186/1471-2407-12-344
PG 12
WC Oncology
SC Oncology
GA 048SW
UT WOS:000311934100001
PM 22873580
ER
PT J
AU Dee, A
McKean-Cowdin, R
Neuhouser, ML
Ulrich, C
Baumgartner, RN
McTiernan, A
Baumgartner, K
Alfano, CM
Ballard-Barbash, R
Bernstein, L
AF Dee, Anne
McKean-Cowdin, Roberta
Neuhouser, Marian L.
Ulrich, Cornelia
Baumgartner, Richard N.
McTiernan, Anne
Baumgartner, Kathy
Alfano, Catherine M.
Ballard-Barbash, Rachel
Bernstein, Leslie
TI DEXA measures of body fat percentage and acute phase proteins among
breast cancer survivors: a Cross-Sectional Analysis
SO BMC CANCER
LA English
DT Article
ID C-REACTIVE PROTEIN; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; SUBCUTANEOUS
ADIPOSE-TISSUE; PHYSICAL-ACTIVITY LEVELS; WEIGHT-LOSS; MASS INDEX; OBESE
WOMEN; INFLAMMATION; CARCINOMA; HEALTH
AB Background: C-reactive protein (CRP) and Serum amyloid A protein (SAA) increases with systemic inflammation and are related to worse survival for breast cancer survivors. This study examines the association between percent body fat and SAA and CRP and the potential interaction with NSAID use and weight change.
Methods: Participants included 134 non-Hispanic white and Hispanic breast cancer survivors from the Health, Eating, Activity, and Lifestyle Study. Body fat percentage, measured with Dual Energy X-ray Absorptiometer (DEXA), and circulating levels of CRP and SAA were obtained 30 months after breast cancer diagnosis.
Results: Circulating concentrations of CRP and SAA were associated with increased adiposity as measured by DEXA after adjustment for age at 24-months, race/ethnicity, dietary energy intake, weight change, and NSAID use. Survivors with higher body fat >= 35% had significantly higher concentrations of CRP (2.01 mg/l vs. 0.85 mg/l) and SAA (6.21 mg/l vs. 4.21 mg/l) compared to non-obese (body fat < 35%). Women who had gained more than 5% of their body weight since breast cancer diagnosis had non-statistically significant higher geometric mean levels of CRP and SAA. Mean levels of CRP and SAA were higher among obese women who were non-users of NSAIDs compared to current users; the association with SAA reached statistical significance (Mean SAA = 7.24, 95% CI 6.13-8.56 for non-NSAID; vs. 4.87; 95% CI 3.95-6.0 for NSAID users respectively).
Conclusions: Breast cancer survivors with higher body fat had higher mean concentrations of CRP and SAA than women with lower body fat. Further assessment of NSAID use and weight control in reducing circulating inflammatory markers among survivors may be worthwhile to investigate in randomized intervention trials as higher inflammatory markers are associated with worse survival.
C1 [Dee, Anne; McKean-Cowdin, Roberta; Bernstein, Leslie] Univ So Calif, Dept Prevent Med, Los Angeles, CA 90089 USA.
[Neuhouser, Marian L.; Ulrich, Cornelia; McTiernan, Anne] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA.
[Alfano, Catherine M.] NCI, Off Canc Survivorship, Div Canc Control & Populat Sci, NIH,DHHS, Bethesda, MD 20892 USA.
[Ballard-Barbash, Rachel] NCI, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Baumgartner, Richard N.; Baumgartner, Kathy] Univ Louisville, Sch Publ Hlth & Informat Sci, Dept Epidemiol & Populat Hlth, Louisville, KY 40202 USA.
[Bernstein, Leslie] City Hope Natl Med Ctr, Beckman Res Inst, Dept Populat Sci, Div Canc Etiol, Duarte, CA 91010 USA.
RP McKean-Cowdin, R (reprint author), Univ So Calif, Dept Prevent Med, Room 418D,2001 Soto St,MC9239, Los Angeles, CA 90089 USA.
EM mckeanco@usc.edu
FU National Institutes of Health: National Cancer Institute
[N01-CN-75036-20, N01-CN-05228, N01-PC-67010, U54-CA116847, R25-CA94880,
N01-PC-35139]; National Institutes of Health [M01-RR-00037]; University
of New Mexico [NCRR M01-RR-0997]; National Cancer Institute [CA 116848,
NO1-PC-35139]; National Institute of Child Health and Human Development
[N01-HD-3-3175]; California Department of Health Services
[050Q-8709-S1528]; California Department of Health Services as part of
the statewide cancer reporting program
FX This work was supported by National Cancer Institute SEER's Special
Study: Weight, Physical Activity, Diet and Breast Cancer Prognosis Study
(Health, Eating, Activity, and Lifestyle Study (HEAL)) NO1-PC-35139.
This project has been supported with funds from the National Institutes
of Health: National Cancer Institute Contract N01-CN-75036-20,
N01-CN-05228, N01-PC-67010, U54-CA116847, R25-CA94880, No. N01-PC-35139
for the Los Angeles HEAL Study; National Institutes of Health Grant No.
M01-RR-00037; University of New Mexico Grant No. NCRR M01-RR-0997;
National Cancer Institute grant CA 116848 for the USC Center for
Transdisciplinary Research on Energetics and Cancer and National
Institute of Child Health and Human Development Contract N01-HD-3-3175
for the Women's CARE Study; and California Department of Health Services
Grant No. 050Q-8709-S1528. The collection of California cancer incidence
data providing the patient base for this publication was supported by
the California Department of Health Services as part of the statewide
cancer reporting program mandated by California Health and Safety Code
Section 103885. The ideas and opinions expressed herein are those of the
authors, and no endorsement by the State of California, Department of
Health Services is intended or should be inferred.
NR 42
TC 4
Z9 4
U1 0
U2 3
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 8
PY 2012
VL 12
AR 343
DI 10.1186/1471-2407-12-343
PG 10
WC Oncology
SC Oncology
GA 042WI
UT WOS:000311501900001
PM 22873489
ER
PT J
AU Mitsunaga, M
Nakajima, T
Sano, K
Kramer-Marek, G
Choyke, PL
Kobayashi, H
AF Mitsunaga, Makoto
Nakajima, Takahito
Sano, Kohei
Kramer-Marek, Gabriela
Choyke, Peter L.
Kobayashi, Hisataka
TI Immediate in vivo target-specific cancer cell death after near infrared
photoimmunotherapy
SO BMC CANCER
LA English
DT Article
DE Photoimmunotherapy; Theranostics; Cell death; Epidermal growth factor
receptor; Molecular targeting; Monoclonal antibody; Bioluminescence
imaging
ID BIOLUMINESCENCE; GFP; DISCOVERY; APOPTOSIS; DYNAMICS; MODELS; MOUSE;
VITRO; ATP
AB Background: Near infrared (NIR) photoimmunotherapy (PIT) is a new type of cancer treatment based on a monoclonal antibody (mAb)-NIR phthalocyanine dye, (IR700) conjugate. In vitro cancer-specific cell death occurs during NIR light exposure in cells previously incubated with mAb-IR700 conjugates. However, documenting rapid cell death in vivo is more difficult.
Methods: A luciferase-transfected breast cancer cell (epidermal growth factor receptor+, MDA-MB-468luc cells) was produced and used for both in vitro and in vivo experiments for monitoring the cell killing effect of PIT. After validation of cytotoxicity with NIR exposure up to 8 J/cm(2) in vitro, we employed an orthotopic breast cancer model of bilateral MDA-MB-468luc tumors in female athymic mice, which subsequently received a panitumumab-IR700 conjugate in vivo. One side was used as a control, while the other was treated with NIR light of dose ranging from 50 to 150 J/cm(2). Bioluminescence imaging (BLI) was performed before and after PIT.
Results: Dose-dependent cell killing and regrowth was successfully monitored by the BLI signal in vitro. Although tumor sizes were unchanged, BLI signals decreased by > 95% immediately after PIT in vivo when light intensity was high (> 100 J/cm(2)), however, in mice receiving lower intensity NIR (50 J/cm(2)), tumors recurred with gradually increasing BLI signal.
Conclusion: PIT induced massive cell death of targeted tumor cells immediately after exposure of NIR light that was demonstrated with BLI in vivo.
C1 [Mitsunaga, Makoto; Nakajima, Takahito; Sano, Kohei; Choyke, Peter L.; Kobayashi, Hisataka] NCI, Mol Imaging Program, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Kramer-Marek, Gabriela] NCI, Radiat Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Kobayashi, H (reprint author), NCI, Mol Imaging Program, Ctr Canc Res, NIH, Bldg 10,Room B3B69,MSC1088, Bethesda, MD 20892 USA.
EM kobayash@mail.nih.gov
FU Intramural Research Program of the National Institutes of Health,
National Cancer Institute, Center for Cancer Research
FX This research was supported by the Intramural Research Program of the
National Institutes of Health, National Cancer Institute, Center for
Cancer Research.
NR 19
TC 28
Z9 28
U1 0
U2 19
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 8
PY 2012
VL 12
AR 345
DI 10.1186/1471-2407-12-345
PG 8
WC Oncology
SC Oncology
GA 042WM
UT WOS:000311502300001
PM 22873679
ER
PT J
AU Tam, J
Cinar, R
Liu, J
Godlewski, G
Wesley, D
Jourdan, T
Szanda, G
Mukhopadhyay, B
Chedester, L
Liow, JS
Innis, RB
Cheng, KJ
Rice, KC
Deschamps, JR
Chorvat, RJ
McElroy, JF
Kunos, G
AF Tam, Joseph
Cinar, Resat
Liu, Jie
Godlewski, Grzegorz
Wesley, Daniel
Jourdan, Tony
Szanda, Gergo
Mukhopadhyay, Bani
Chedester, Lee
Liow, Jeih-San
Innis, Robert B.
Cheng, Kejun
Rice, Kenner C.
Deschamps, Jeffrey R.
Chorvat, Robert J.
McElroy, John F.
Kunos, George
TI Peripheral Cannabinoid-1 Receptor Inverse Agonism Reduces Obesity by
Reversing Leptin Resistance
SO CELL METABOLISM
LA English
DT Article
ID DIET-INDUCED OBESITY; ENERGY-BALANCE; CB1 RECEPTOR; ENDOCANNABINOID
SYSTEM; ADIPOSE-TISSUE; FOOD-INTAKE; INSULIN; CELLS; MICE; METABOLISM
AB Obesity-related leptin resistance manifests in loss of leptin's ability to reduce appetite and increase energy expenditure. Obesity is also associated with increased activity of the endocannabinoid system, and CBI receptor (CB1R) inverse agonists reduce body weight and the associated metabolic complications, although adverse neuropsychiatric effects halted their therapeutic development. Here we show that in mice with diet-induced obesity (DIO), the peripherally restricted Ca1R inverse agonist JD5037 is equieffective with its brain-penetrant parent compound in reducing appetite, body weight, hepatic steatosis, and insulin resistance, even though it does not occupy central CB1R or induce related behaviors. Appetite and weight reduction by JD5037 are mediated by resensitizing DIO mice to endogenous leptin through reversing the hyperleptinemia by decreasing leptin expression and secretion by adipocytes and increasing leptin clearance via the kidney. Thus, inverse agonism at peripheral CB1R not only improves cardiometabolic risk in obesity but has antiobesity effects by reversing leptin resistance.
C1 [Tam, Joseph; Cinar, Resat; Liu, Jie; Godlewski, Grzegorz; Wesley, Daniel; Jourdan, Tony; Szanda, Gergo; Mukhopadhyay, Bani; Chedester, Lee; Kunos, George] NIAAA, Lab Physiol Studies, NIH, Bethesda, MD 20892 USA.
[Liow, Jeih-San; Innis, Robert B.] NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA.
[Cheng, Kejun; Rice, Kenner C.] NIDA, Chem Biol Res Branch, NIH, Bethesda, MD 20892 USA.
[Deschamps, Jeffrey R.] USN, Res Lab, Washington, DC 20375 USA.
[Chorvat, Robert J.; McElroy, John F.] Jenrin Discovery Inc, Wilmington, DE 19810 USA.
RP Tam, J (reprint author), NIAAA, Lab Physiol Studies, NIH, Bethesda, MD 20892 USA.
EM tamy@mail.nih.gov; george.kunos@nih.gov
OI Deschamps, Jeffrey/0000-0001-5845-0010; CINAR, RESAT/0000-0002-8597-7253
FU National Institute on Alcohol Abuse and Alcoholism, NIH; Jenrin
Discovery, Inc.
FX This work was supported by intramural funds from the National Institute
on Alcohol Abuse and Alcoholism, NIH. Design and synthesis of JD5037 was
funded by Jenrin Discovery, Inc. J.F.M. and R.J.C. hold a patent on
JD5037. We thank V. Pike and C. Morris for support and advice with the
PET studies, and M. Allen, R. Schwartzbeck, A. Noguchi, D. Springer, and
R. Kechrid for their assistance with the animal studies.
NR 61
TC 103
Z9 106
U1 3
U2 14
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1550-4131
J9 CELL METAB
JI Cell Metab.
PD AUG 8
PY 2012
VL 16
IS 2
BP 167
EP 179
DI 10.1016/j.cmet.2012.07.002
PG 13
WC Cell Biology; Endocrinology & Metabolism
SC Cell Biology; Endocrinology & Metabolism
GA 990FB
UT WOS:000307615300007
PM 22841573
ER
PT J
AU Yamamoto, S
Monosov, IE
Yasuda, M
Hikosaka, O
AF Yamamoto, Shinya
Monosov, Ilya E.
Yasuda, Masaharu
Hikosaka, Okihide
TI What and Where Information in the Caudate Tail Guides Saccades to Visual
Objects
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
ID FRONTAL EYE FIELD; LATERAL INTRAPARIETAL AREA; PRIMATE PREFRONTAL
CORTEX; NIGRA PARS RETICULATA; SUBSTANTIA-NIGRA; SUPERIOR COLLICULUS;
RHESUS-MONKEY; CORTICOSTRIATAL PROJECTIONS; HORSERADISH-PEROXIDASE;
OCULOMOTOR FUNCTIONS
AB We understand the world by making saccadic eye movements to various objects. However, it is unclear how a saccade can be aimed at a particular object, because two kinds of visual information, what the object is and where it is, are processed separately in the dorsal and ventral visual cortical pathways. Here, we provide evidence suggesting that a basal ganglia circuit through the tail of the monkey caudate nucleus (CDt) guides such object-directed saccades. First, many CDt neurons responded to visual objects depending on where and what the objects were. Second, electrical stimulation in the CDt induced saccades whose directions matched the preferred directions of neurons at the stimulation site. Third, many CDt neurons increased their activity before saccades directed to the preferred objects and directions of the neurons in a free-viewing condition. Our results suggest that CDt neurons receive both "what" and "where" information and guide saccades to visual objects.
C1 [Yamamoto, Shinya] Natl Inst Adv Ind Sci & Technol, Human Technol Res Inst, Tsukuba, Ibaraki 3058568, Japan.
[Yamamoto, Shinya; Monosov, Ilya E.; Yasuda, Masaharu; Hikosaka, Okihide] NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA.
RP Yamamoto, S (reprint author), Natl Inst Adv Ind Sci & Technol, Human Technol Res Inst, 1-1-1 Umezono, Tsukuba, Ibaraki 3058568, Japan.
EM yamamoto-s@aist.go.jp
RI Yamamoto, Shinya/S-3134-2016
OI Yamamoto, Shinya/0000-0002-0505-8848
FU National Eye Institute
FX This work was supported by the intramural research program at the
National Eye Institute. We thank E. S. Bromberg-Martin, S. Hong, H. Kim,
and Y. Tachibana for valuable discussions, and A. Hays, J. W. McClurkin,
B. Nagy, A. M. Nichols, D. Parker, T. W. Ruffner, M. K. Smith, G.
Tansey, N. Phipps, C. Zhu, F. Ye, and D. Leopold for technical
assistance.
NR 44
TC 31
Z9 31
U1 2
U2 9
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 8
PY 2012
VL 32
IS 32
BP 11005
EP 11016
DI 10.1523/JNEUROSCI.0828-12.2012
PG 12
WC Neurosciences
SC Neurosciences & Neurology
GA 990OJ
UT WOS:000307640000021
PM 22875934
ER
PT J
AU Bossart, KN
Rockx, B
Feldmann, F
Brining, D
Scott, D
LaCasse, R
Geisbert, JB
Feng, YR
Chan, YP
Hickey, AC
Broder, CC
Feldmann, H
Geisbert, TW
AF Bossart, Katharine N.
Rockx, Barry
Feldmann, Friederike
Brining, Doug
Scott, Dana
LaCasse, Rachel
Geisbert, Joan B.
Feng, Yan-Ru
Chan, Yee-Peng
Hickey, Andrew C.
Broder, Christopher C.
Feldmann, Heinz
Geisbert, Thomas W.
TI A Hendra Virus G Glycoprotein Subunit Vaccine Protects African Green
Monkeys from Nipah Virus Challenge
SO SCIENCE TRANSLATIONAL MEDICINE
LA English
DT Article
ID TRANSMISSION; BANGLADESH; INFECTION; HENIPAVIRUSES; BATS
AB In the 1990s, Hendra virus and Nipah virus (NiV), two closely related and previously unrecognized paramyxoviruses that cause severe disease and death in humans and a variety of animals, were discovered in Australia and Malaysia, respectively. Outbreaks of disease have occurred nearly every year since NiV was first discovered, with case fatality ranging from 10 to 100%. In the African green monkey (AGM), NiV causes a severe lethal respiratory and/or neurological disease that essentially mirrors fatal human disease. Thus, the AGM represents a reliable disease model for vaccine and therapeutic efficacy testing. We show that vaccination of AGMs with a recombinant subunit vaccine based on the henipavirus attachment G glycoprotein affords complete protection against subsequent NiV infection with no evidence of clinical disease, virus replication, or pathology observed in any challenged subjects. Success of the recombinant subunit vaccine in nonhuman primates provides crucial data in supporting its further preclinical development for potential human use.
C1 [Feng, Yan-Ru; Chan, Yee-Peng; Broder, Christopher C.] Uniformed Serv Univ Hlth Sci, Dept Microbiol & Immunol, Bethesda, MD 20814 USA.
[Feldmann, Heinz] Univ Manitoba, Dept Med Microbiol, Winnipeg, MB R3T 2N2, Canada.
[Geisbert, Joan B.; Geisbert, Thomas W.] Univ Texas Med Branch, Galveston Natl Lab, Galveston, TX 77550 USA.
[Geisbert, Joan B.; Geisbert, Thomas W.] Univ Texas Med Branch, Dept Microbiol & Immunol, Galveston, TX 77550 USA.
[Brining, Doug; Scott, Dana; LaCasse, Rachel] NIAID, Rocky Mt Vet Branch, Div Intramural Res, NIH,Rocky Mt Labs, Hamilton, MT 59840 USA.
[Feldmann, Friederike] NIH, Off Operat & Management, Rocky Mt Labs, Hamilton, MT 59840 USA.
[Rockx, Barry] Univ Texas Med Branch, Sealy Ctr Vaccine Dev, Dept Pathol & Microbiol, Galveston, TX 77555 USA.
[Rockx, Barry] Univ Texas Med Branch, Dept Immunol, Galveston, TX 77555 USA.
[Rockx, Barry; Feldmann, Heinz] NIH, Virol Lab, Rocky Mt Labs, Hamilton, MT 59840 USA.
[Bossart, Katharine N.; Hickey, Andrew C.] Boston Univ, Sch Med, Nat Emerging Infect Dis Labs Inst, Boston, MA 02118 USA.
[Bossart, Katharine N.; Hickey, Andrew C.] Boston Univ, Sch Med, Dept Microbiol, Boston, MA 02118 USA.
RP Broder, CC (reprint author), Uniformed Serv Univ Hlth Sci, Dept Microbiol & Immunol, Bethesda, MD 20814 USA.
EM christopher.broder@usuhs.edu
OI Bossart, Katharine/0000-0001-6886-6896
FU Intramural Research Program of the NIAID, NIH; Department of Health and
Human Services, NIH [AI082121, AI057159, AI054715, AI077995]; Intramural
Biodefense Program of the NIAID
FX These studies were supported in part by the Intramural Research Program
of the NIAID, NIH, and in part by the Department of Health and Human
Services, NIH, grants AI082121 and AI057159 to T.W.G.; AI054715 and
AI077995 to C.C.B.; and the Intramural Biodefense Program of the NIAID.
NR 27
TC 21
Z9 22
U1 2
U2 19
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 1946-6234
J9 SCI TRANSL MED
JI Sci. Transl. Med.
PD AUG 8
PY 2012
VL 4
IS 146
AR 146ra107
DI 10.1126/scitranslmed.3004241
PG 8
WC Cell Biology; Medicine, Research & Experimental
SC Cell Biology; Research & Experimental Medicine
GA 990OV
UT WOS:000307641300003
PM 22875827
ER
PT J
AU Szabo, C
Pacher, P
AF Szabo, Csaba
Pacher, Pal
TI The Outsiders: Emerging Roles of Ectonucleotidases in Inflammation
SO SCIENCE TRANSLATIONAL MEDICINE
LA English
DT Article
ID ADENOSINE PRODUCTION; ADENINE-NUCLEOTIDES; DEFICIENT MICE;
UP-REGULATION; LUNG INJURY; CD73; ECTO-5'-NUCLEOTIDASE;
CD73/ECTO-5'-NUCLEOTIDASE; MECHANISM; METHOTREXATE
AB Research on the biological roles of ectonucleoidases has revealed that CD73, an ecto-5' nucleotidase, plays a special role in the extracellular conversion of adenosine monophosphate to adenosine-specifically, as a checkpoint that determines whether the extracellular environment is proinflammatory (characterized by adenosine 5'-triphosphate-mediated responses) or anti-inflammatory (adenosine-mediated responses). Inactivating or inhibiting CD73 attenuates the extracellular formation of adenosine, exacerbating the severity of various inflammatory diseases. In this issue of Science Translational Medicine, Flogel and colleagues showed that CD73 can be pharmacologically exploited to convert an inactive adenosine precursor to an active, anti-inflammatory adenosine analog. In addition to attenuating inflammation associated with collagen-induced arthritis in a mouse model, this prodrug approach was site-selective, because the metabolic conversion relies on CD73, which is up-regulated in the inflammatory locus (the joint).
C1 [Szabo, Csaba] Univ Texas Galveston, Med Branch, Dept Anesthesiol, Galveston, TX 77555 USA.
[Pacher, Pal] NIAAA, NIH, Bethesda, MD 20892 USA.
RP Szabo, C (reprint author), Univ Texas Galveston, Med Branch, Dept Anesthesiol, Galveston, TX 77555 USA.
EM szabocsaba@aol.com; pacher@mail.nih.gov
RI Pacher, Pal/B-6378-2008
OI Pacher, Pal/0000-0001-7036-8108
FU Shriners of North America; Juvenile Diabetes Foundation; American
Diabetes Association; Intramural Research Program of NIH/NIAAA
FX C.S. is supported by the Shriners of North America, the Juvenile
Diabetes Foundation, and the American Diabetes Association. P.P. is
supported by the Intramural Research Program of NIH/NIAAA.
NR 31
TC 1
Z9 1
U1 0
U2 4
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 1946-6234
J9 SCI TRANSL MED
JI Sci. Transl. Med.
PD AUG 8
PY 2012
VL 4
IS 146
AR 146ps14
DI 10.1126/scitranslmed.3004378
PG 4
WC Cell Biology; Medicine, Research & Experimental
SC Cell Biology; Research & Experimental Medicine
GA 990OV
UT WOS:000307641300001
PM 22875826
ER
PT J
AU Kit, BK
Carroll, MD
Lacher, DA
Sorlie, PD
DeJesus, JM
Ogden, CL
AF Kit, Brian K.
Carroll, Margaret D.
Lacher, David A.
Sorlie, Paul D.
DeJesus, Janet M.
Ogden, Cynthia L.
TI Trends in Serum Lipids Among US Youths Aged 6 to 19 Years, 1988-2010
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Article
ID DENSITY-LIPOPROTEIN CHOLESTEROL; CARDIOVASCULAR RISK-FACTORS;
UNITED-STATES; CHILDREN; ADOLESCENTS; CHILDHOOD; ATHEROSCLEROSIS;
PREVALENCE; ADULTHOOD; SMOKING
AB Context For more than 20 years, primary prevention of coronary heart disease has included strategies intended to improve overall serum lipid concentrations among youths.
Objective To examine trends in lipid concentrations among youths from 19881994 through 2007-2010.
Design, Setting, and Participants Cross-sectional analysis of serum lipid concentrations among 16 116 youths aged 6 to 19 years who participated in the nationally representative National Health and Nutrition Examination Survey during 3 time periods: 1988-1994, 1999-2002, and 2007-2010.
Main Outcome Measures Among all youths, mean serum total cholesterol (TC), non-high-density lipoprotein cholesterol (non-HDL-C), high-density lipoprotein cholesterol (HDL-C); and among adolescents only, low-density lipoprotein cholesterol (LDL-C) and geometric mean triglyceride levels. Trends in adverse lipid concentrations are reported for TC levels of 200 mg/dL and greater, non-HDL-C levels of 145 mg/dL and greater, HDL-C levels of less than 40 mg/dL, LDL-C levels of 130 mg/dL and greater, and triglyceride levels of 130 mg/dL and greater.
Results Among youths aged 6 to 19 years between 1988-1994 and 2007-2010, there was a decrease in mean TC (from 165 mg/dL [95% CI, 164-167] to 160 mg/dL [95% CI, 158-161]; P<.001) and a decrease in the prevalence of elevated TC (from 11.3% [95% CI, 9.8%-12.7%] to 8.1% [95% CI, 6.7%-9.5%]; P=.002). Mean HDL-C significantly increased between 1988-1994 and 2007-2010, but the prevalence of low HDL-C did not change. Mean non-HDL-C and prevalence of elevated non-HDL-C both significantly decreased over the study period. In 2007-2010, 22% (95% CI, 20.3%-23.6%) of youths had either a low HDL-C level or high non-HDL-C, which was lower than the 27.2% (95% CI, 24.6%-29.7%) in 1988-1994 (P=.001). Among adolescents (aged 12-19 years) between 1988-1994 and 2007-2010, there was a decrease in mean LDL-C (from 95 mg/dL [95% CI, 92-98] to 90 mg/dL [95% CI, 88-91]; P=.003) and a decrease in geometric mean triglycerides (from 82 mg/dL [95% CI, 78-86] to 73 mg/dL [95% CI, 70-76]; P<.001). Prevalence of elevated LDL-C and triglycerides between 1988-1994 and 2007-2010 also significantly decreased.
Conclusions Between 1988-1994 and 2007-2010, a favorable trend in serum lipid concentrations was observed among youths in the United States but almost 1 in 10 had elevated TC in 2007-2010. JAMA. 2012;308(6):591-600
C1 [Kit, Brian K.; Carroll, Margaret D.; Lacher, David A.; Ogden, Cynthia L.] Ctr Dis Control & Prevent, Div Hlth & Nutr Examinat Surveys, Natl Ctr Hlth Stat, Hyattsville, MD 20782 USA.
[Kit, Brian K.] US PHS, Rockville, MD USA.
[Sorlie, Paul D.] NHLBI, Div Cardiovasc Sci, NIH, Bethesda, MD 20892 USA.
[DeJesus, Janet M.] NHLBI, Div Applicat Res Discoveries, NIH, Bethesda, MD 20892 USA.
RP Kit, BK (reprint author), Ctr Dis Control & Prevent, Div Hlth & Nutr Examinat Surveys, Natl Ctr Hlth Stat, 3311 Toledo Rd,MS PO8,Room 4419, Hyattsville, MD 20782 USA.
EM bkit@cdc.gov
FU National Heart, Lung, and Blood Institute, National Institutes of Health
[Y1-HC-8039]
FX The laboratory analysis of the lipids described in this paper was funded
by the National Heart, Lung, and Blood Institute, National Institutes of
Health, Intra-agency Agreement number Y1-HC-8039.
NR 53
TC 47
Z9 49
U1 1
U2 7
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 0098-7484
EI 1538-3598
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD AUG 8
PY 2012
VL 308
IS 6
BP 591
EP 600
DI 10.1001/jama.2012.9136
PG 10
WC Medicine, General & Internal
SC General & Internal Medicine
GA 984YA
UT WOS:000307228400026
PM 22871871
ER
PT J
AU Monterroso, B
Rivas, G
Minton, AP
AF Monterroso, Begona
Rivas, German
Minton, Allen P.
TI An Equilibrium Model for the Mg2+-Linked Self-Assembly of FtsZ in the
Presence of GTP or a GTP Analogue
SO BIOCHEMISTRY
LA English
DT Article
ID CELL-DIVISION; PROTEIN FTSZ; POLYMERIZATION; FILAMENTS; POLYMERS
AB The concerted formation of a narrow distribution of oligomeric Fts2 species in the presence of GTP or a GTP analogue under close to physiological conditions (neutral pH and 0.5 M K+) has been characterized recently by various biophysical methods [Monterroso, B., et al. (2012) Biochemistry 51, 4541-4550] An equilibrium model may semiquantitatively account for the results of this study; in the model, FtsZ self-associates in a noncooperative fashion to form linear fibrils, that upon increasing to a certain size exhibit an increasing tendency to form closed cyclic fibrils, as previously suggested [Gonzalez, J. M., et al. (2005) Proc. Natl. Acad. Sci. U.S.A. 102, 1895-1900]. The closed cyclic fibrils are formed when the natural curvature and flexibility of a linear oligomer bring the ends of a linear fiber sufficiently close to overcome the entropic barrier to loop closure. The size distribution of cyclic oligomers is thus a reflection of the tendency toward curvature of linear fibrils of FtsZ under the conditions used in these experiments.
C1 [Monterroso, Begona; Rivas, German] CSIC, Ctr Invest Biol, Chem & Phys Biol Program, Madrid, Spain.
[Minton, Allen P.] NIDDK, Sect Phys Biochem, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA.
RP Rivas, G (reprint author), CSIC, Ctr Invest Biol, Chem & Phys Biol Program, Madrid, Spain.
EM grivas@cib.csic.es; minton@helix.nih.gov
RI Monterroso, Begona/J-9748-2014;
OI Monterroso, Begona/0000-0003-2538-084X; Minton,
Allen/0000-0001-8459-1247; Rivas, German/0000-0003-3450-7478
FU Spanish Ministerio de Ciencia e Innovacion [BIO2008-04478-C03,
BIO2011-28941-C03-03]; European Commission [HEALTH-F3-2009-223432];
Human Frontiers Science Program [RGP0050/2010-C102]; Comunidad de Madrid
[S-BIO-0260/2006]; National Institute of Diabetes and Digestive and
Kidney Diseases
FX This work was supported by the Spanish Ministerio de Ciencia e
Innovacion through Grants BIO2008-04478-C03 and BIO2011-28941-C03-03, by
the European Commission through Contract HEALTH-F3-2009-223432, by the
Human Frontiers Science Program through Grant RGP0050/2010-C102, and by
the Comunidad de Madrid through Grant S-BIO-0260/2006 to G.R. B.M. is a
JAE postdoctoral associate from the European Social Fund and the Spanish
Consejo Superior de Investigaciones Cientificas (CSIC). The research of
A.P.M. is supported by the Intramural Research Program of the National
Institute of Diabetes and Digestive and Kidney Diseases.
NR 13
TC 6
Z9 6
U1 1
U2 8
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0006-2960
J9 BIOCHEMISTRY-US
JI Biochemistry
PD AUG 7
PY 2012
VL 51
IS 31
BP 6108
EP 6113
DI 10.1021/bi300891q
PG 6
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 984AI
UT WOS:000307159400008
PM 22809122
ER
PT J
AU Prustel, T
Meier-Schellersheim, M
AF Pruestel, Thorsten
Meier-Schellersheim, Martin
TI Exact Green's function of the reversible diffusion-influenced reaction
for an isolated pair in two dimensions
SO JOURNAL OF CHEMICAL PHYSICS
LA English
DT Article
ID BROWNIAN-MOTION; DYNAMICS
AB We derive an exact Green's function of the diffusion equation for a pair of disk-shaped interacting particles in two dimensions subject to a backreaction boundary condition. Furthermore, we use the obtained function to calculate exact expressions for the survival probability and the time-dependent rate coefficient for the initially unbound pair and the survival probability of the bound state. The derived expressions will be of particular utility for the description of reversible membrane-bound reactions in cell biology. [http://dx.doi.org/10.1063/1.4737662]
C1 [Pruestel, Thorsten; Meier-Schellersheim, Martin] NIAID, Lab Syst Biol, NIH, Bethesda, MD 20892 USA.
RP Prustel, T (reprint author), NIAID, Lab Syst Biol, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM prustelt@niaid.nih.gov; mms@niaid.nih.gov
FU Intramural Research Program of the NIH, National Institute of Allergy
and Infectious Diseases
FX This research was supported by the Intramural Research Program of the
NIH, National Institute of Allergy and Infectious Diseases. We would
like to thank Bastian R. Angermann and Frederick Klauschen for helpful
discussions.
NR 28
TC 6
Z9 6
U1 0
U2 10
PU AMER INST PHYSICS
PI MELVILLE
PA CIRCULATION & FULFILLMENT DIV, 2 HUNTINGTON QUADRANGLE, STE 1 N O 1,
MELVILLE, NY 11747-4501 USA
SN 0021-9606
J9 J CHEM PHYS
JI J. Chem. Phys.
PD AUG 7
PY 2012
VL 137
IS 5
AR 054104
DI 10.1063/1.4737662
PG 7
WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical
SC Chemistry; Physics
GA 994HM
UT WOS:000307921500007
PM 22894329
ER
PT J
AU Deveney, CM
Connolly, ME
Jenkins, SE
Kim, P
Fromm, SJ
Brotman, MA
Pine, DS
Leibenluft, E
AF Deveney, Christen M.
Connolly, Megan E.
Jenkins, Sarah E.
Kim, Pilyoung
Fromm, Stephen J.
Brotman, Melissa A.
Pine, Daniel S.
Leibenluft, Ellen
TI Striatal dysfunction during failed motor inhibition in children at risk
for bipolar disorder
SO PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY
LA English
DT Article
DE Bipolar disorder; Motor inhibition; Magnetic resonance imaging;
Population at risk
ID SEVERE MOOD DYSREGULATION; RESPONSE-INHIBITION; 1ST-DEGREE RELATIVES;
PREFRONTAL CORTEX; WORKING-MEMORY; RATING-SCALE; IMPULSIVITY; ATTENTION;
DEFICITS; ADOLESCENTS
AB Background: A better understanding of the neural underpinnings of bipolar disorder (BD) can be obtained by examining brain activity in symptom-free individuals at risk for BD. This study examined the neural correlates of motor inhibition in a sample of symptom-free youths at familial risk for BD.
Methods: 19 euthymic youths with BD, 13 asymptomatic youths with a first-degree relative with BD, and 21 healthy comparison children completed the stop signal task in a 3 T scanner.
Results: Children at familial risk for BD exhibited increased putamen activation during unsuccessful inhibition that distinguished them from both healthy and BD children. Youths with BD exhibited reduced activation of the right nucleus accumbens during unsuccessful inhibition as compared to the other participant groups.
Conclusions: Striatal activation patterns differ between youths at risk for BD and healthy comparison children during a motor inhibition task. Published by Elsevier Inc.
C1 [Deveney, Christen M.] NIMH, Sect Bipolar Spectrum Disorders, Emot & Dev Branch, NIH,US Dept HHS, Bethesda, MD 20892 USA.
RP Deveney, CM (reprint author), NIMH, Sect Bipolar Spectrum Disorders, Emot & Dev Branch, NIH,US Dept HHS, 15 K N Dr,MSC 2670, Bethesda, MD 20892 USA.
EM deveneycm@mail.nih.gov
RI Brotman, Melissa/H-7409-2013
FU Intramural Research Program of the National Institute of Mental Health,
National Institutes of Health
FX This work was supported by the Intramural Research Program of the
National Institute of Mental Health, National Institutes of Health. The
authors have no conflicts to disclose. We thank the children and
families for their participation which made this research possible. We
also thank the staff of the Emotion and Development Branch at NIMH.
NR 41
TC 12
Z9 12
U1 2
U2 6
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0278-5846
J9 PROG NEURO-PSYCHOPH
JI Prog. Neuro-Psychopharmacol. Biol. Psychiatry
PD AUG 7
PY 2012
VL 38
IS 2
BP 127
EP 133
DI 10.1016/j.pnpbp.2012.02.014
PG 7
WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA 985IY
UT WOS:000307258300004
PM 22414616
ER
PT J
AU Solier, S
Kohn, KW
Scroggins, B
Xu, WP
Trepel, J
Neckers, L
Pommier, Y
AF Solier, Stephanie
Kohn, Kurt W.
Scroggins, Bradley
Xu, Wanping
Trepel, Jane
Neckers, Leonard
Pommier, Yves
TI Heat shock protein 90 alpha (HSP90 alpha), a substrate and chaperone of
DNA-PK necessary for the apoptotic response
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE programmed cell death; caspase; camptothecin; staurosporine; FasL
ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; DAMAGE RESPONSE; HSP90 CHAPERONE;
INHIBITOR NU7441; TOPOISOMERASE-I; HISTONE H2AX; CANCER; KINASE; CELLS;
TRAIL
AB The "apoptotic ring" is characterized by the phosphorylation of histone H2AX at serine 139 (gamma-H2AX) by DNA-dependent protein kinase (DNA-PK). The gamma-H2AX apoptotic ring differs from the nuclear foci patterns observed in response to DNA-damaging agents. It contains phosphorylated DNA damage response proteins including activated Chk2, activated ATM, and activated DNA-PK itself but lacks MDC1 and 53BP1, which are required to initiate DNA repair. Because DNA-PK can phosphorylate heat shock protein 90 alpha (HSP90 alpha) in biochemical assays, we investigated whether HSP90 alpha is involved in the apoptotic ring. Here we show that HSP90 alpha is phosphorylated by DNA-PK on threonines 5 and 7 early during apoptosis and that both phosphorylated HSP90 alpha and DNA-PK colocalize in the apoptotic ring. We also show that DNA-PK is a client of HSP90 alpha and that HSP90 alpha is required for full DNA-PK activation, gamma-H2AX formation, DNA fragmentation, and apoptotic body formation. In contrast, HSP90 inhibition by geldanamycin markedly enhances TRAIL-induced DNA-PK and H2AX activation. Together, our results reveal that HSP90 alpha is a substrate and chaperone of DNA-PK in the apoptotic response. The response of phosphorylated HSP90 alpha to TRAIL and its localization to the gamma-H2AX ring represent epigenetic features of apoptosis that offer insights for studying and monitoring nuclear apoptosis.
C1 [Solier, Stephanie; Kohn, Kurt W.; Pommier, Yves] NCI, Mol Pharmacol Lab, Ctr Canc Res, Bethesda, MD 20892 USA.
[Scroggins, Bradley; Xu, Wanping; Neckers, Leonard] NCI, Urol Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Trepel, Jane] NCI, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Pommier, Y (reprint author), NCI, Mol Pharmacol Lab, Ctr Canc Res, Bethesda, MD 20892 USA.
EM pommier@nih.gov
FU Center for Cancer Research Intramural Research Program of the National
Cancer Institute, National Institutes of Health
FX These studies were supported by the Center for Cancer Research
Intramural Research Program of the National Cancer Institute, National
Institutes of Health.
NR 52
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U1 0
U2 8
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 7
PY 2012
VL 109
IS 32
BP 12866
EP 12872
DI 10.1073/pnas.1203617109
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 989HU
UT WOS:000307551700015
PM 22753480
ER
PT J
AU Degnan, PH
Pusey, AE
Lonsdorf, EV
Goodall, J
Wroblewski, EE
Wilson, ML
Rudicell, RS
Hahn, BH
Ochman, H
AF Degnan, Patrick H.
Pusey, Anne E.
Lonsdorf, Elizabeth V.
Goodall, Jane
Wroblewski, Emily E.
Wilson, Michael L.
Rudicell, Rebecca S.
Hahn, Beatrice H.
Ochman, Howard
TI Factors associated with the diversification of the gut microbial
communities within chimpanzees from Gombe National Park
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
ID 16S RIBOSOMAL-RNA; GASTROINTESTINAL-TRACT; INTESTINAL MICROBIOTA;
DIVERSITY; EVOLUTION; PATTERNS; ECOLOGY; PROJECT
AB The gastrointestinal tract harbors large and diverse populations of bacteria that vary among individuals and within individuals over time. Numerous internal and external factors can influence the contents of these microbial communities, including diet, geography, physiology, and the extent of contact among hosts. To investigate the contributions of such factors to the variation and changes in gut microbial communities, we analyzed the distal gut microbiota of individual chimpanzees from two communities in Gombe National Park, Tanzania. These samples, which were derived from 35 chimpanzees, many of whom have been monitored for multiple years, provide an unusually comprehensive longitudinal depth for individuals of known genetic relationships. Although the composition of the great-ape microbiota has been shown to codiversify with host species, indicating that host genetics and phylogeny have played a major role in its differentiation over evolutionary timescales, the geneaological relationships of individual chimpanzees did not coincide with the similarity in their gut microbial communities. However, the inhabitants from adjacent chimpanzee communities could be distinguished based on the contents of their gut microbiota. Despite the broad similarity of community members, as would be expected from shared diet or interactions, long-term immigrants to a community often harbored the most distinctive gut microbiota, suggesting that individuals retain hallmarks of their previous gut microbial communities for extended periods. This pattern was reinforced in several chimpanzees sampled over long temporal scales, in which the major constituents of the gut microbiota were maintained for nearly a decade.
C1 [Degnan, Patrick H.; Ochman, Howard] Yale Univ, Dept Ecol & Evolutionary Biol, New Haven, CT 06520 USA.
[Pusey, Anne E.] Duke Univ, Dept Evolutionary Anthropol, Durham, NC 27708 USA.
[Lonsdorf, Elizabeth V.] Franklin & Marshall Coll, Dept Psychol, Lancaster, PA 17604 USA.
[Goodall, Jane] Jane Goodall Inst, Gombe Stream Res Ctr, Kigoma, Tanzania.
[Goodall, Jane] Jane Goodall Inst, Arlington, VA 22203 USA.
[Wroblewski, Emily E.] Stanford Univ, Sch Med, Dept Biol Struct, Stanford, CA 94305 USA.
[Wilson, Michael L.] Univ Minnesota, Dept Anthropol, Minneapolis, MN 55455 USA.
[Wilson, Michael L.] Univ Minnesota, Dept Ecol Evolut & Behav, St Paul, MN 55108 USA.
[Rudicell, Rebecca S.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Hahn, Beatrice H.] Univ Penn, Perelman Sch Med, Dept Med, Philadelphia, PA 19104 USA.
[Hahn, Beatrice H.] Univ Penn, Perelman Sch Med, Dept Microbiol, Philadelphia, PA 19104 USA.
RP Ochman, H (reprint author), Yale Univ, Dept Ecol & Evolutionary Biol, New Haven, CT 06520 USA.
EM howard.ochman@yale.edu
FU National Institutes of Health [R01 AI50529, R01 AI58715, R01 GM74738,
R01 GM101209]; University of Alabama at Birmingham Center for AIDS
Research Grant [P30 AI 27767]; National Science Foundation; Howard
Hughes Medical Institute Med-into-Grad Fellowship; National Science
Foundation [BSC-0648481]
FX PCR and sequencing primers for iTag analysis were generously provided by
Rob Knight (University of Colorado) and Integrated DNA Technologies. We
thank the Jane Goodall Institute and the National Science Foundation
through Grant BSC-0648481 (to M.L.W.) for supporting collection of
behavioral data and fecal samples from chimpanzees at the Gombe Stream
Research Centre; and the Tanzania Commission for Science and Technology,
the Tanzania Wildlife Research Institute, and the Tanzania National
Parks for permission to conduct research in Gombe. This work was
supported in part by National Institutes of Health Grants R01 AI50529,
R01 AI58715 (to B.H.H.), and R01 GM74738 and R01 GM101209 (to H.O.);
University of Alabama at Birmingham Center for AIDS Research Grant P30
AI 27767; and the National Science Foundation (A.E.P.). R.S.R. was
funded by a Howard Hughes Medical Institute Med-into-Grad Fellowship.
NR 30
TC 39
Z9 39
U1 8
U2 48
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 7
PY 2012
VL 109
IS 32
BP 13034
EP 13039
DI 10.1073/pnas.1110994109
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 989HU
UT WOS:000307551700044
PM 22826227
ER
PT J
AU Andersson, RH
Johnston, A
Herman, PA
Winzer-Serhan, UH
Karavanova, I
Vullhorst, D
Fisahn, A
Buonanno, A
AF Andersson, Richard H.
Johnston, April
Herman, Paul A.
Winzer-Serhan, Ursula H.
Karavanova, Irina
Vullhorst, Detlef
Fisahn, Andre
Buonanno, Andres
TI Neuregulin and dopamine modulation of hippocampal gamma oscillations is
dependent on dopamine D4 receptors
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE fast-spiking interneuron; attention-deficit/hyperactivity disorder;
cognitive enhancers; excitatory/inhibitory balance
ID NETWORK OSCILLATIONS; INTERNEURON NETWORKS; SYNAPTIC PLASTICITY;
PREFRONTAL CORTEX; WORKING-MEMORY; IN-VITRO; SCHIZOPHRENIA; ANTAGONIST;
GENES; MECHANISMS
AB The neuregulin/ErbB signaling network is genetically associated with schizophrenia and modulates hippocampal gamma oscillations-a type of neuronal network activity important for higher brain processes and altered in psychiatric disorders. Because neuregulin-1 (NRG-1) dramatically increases extracellular dopamine levels in the hippocampus, we investigated the relationship between NRG/ErbB and dopamine signaling in hippocampal gamma oscillations. Using agonists for different D1- and D2-type dopamine receptors, we found that the D4 receptor (D4R) agonist PD168077, but not D1/D5 and D2/D3 agonists, increases gamma oscillation power, and its effect is blocked by the highly specific D4R antagonist L-745,870. Using double in situ hybridization and immunofluorescence histochemistry, we show that hippocampal D4R mRNA and protein are more highly expressed in GAD67-positive GABAergic interneurons, many of which express the NRG-1 receptor ErbB4. Importantly, D4 and ErbB4 receptors are coexpressed in parvalbumin-positive basket cells that are critical for gamma oscillations. Last, we report that D4R activation is essential for the effects of NRG-1 on network activity because L-745,870 and the atypical antipsychotic clozapine dramatically reduce the NRG-1-induced increase in gamma oscillation power. This unique link between D4R and ErbB4 signaling on gamma oscillation power, and their coexpression in parvalbumin-expressing interneurons, suggests a cellular mechanism that may be compromised in different psychiatric disorders affecting cognitive control. These findings are important given the association of a DRD4 polymorphism with alterations in attention, working memory, and gamma oscillations, and suggest potential benefits of D4R modulators for targeting cognitive deficits.
C1 [Herman, Paul A.; Karavanova, Irina; Vullhorst, Detlef; Buonanno, Andres] Eunice Shriver Kennedy Natl Inst Child Hlth & Hum, Sect Mol Neurobiol, Bethesda, MD 20892 USA.
[Andersson, Richard H.; Johnston, April; Fisahn, Andre] Karolinska Inst, Neuronal Oscillat Lab, KI Alzheimer Dis Res Ctr, Dept Neurobiol Care Sci & Soc, S-14186 Stockholm, Sweden.
[Winzer-Serhan, Ursula H.] Texas A&M Univ Syst, Dept Neurosci & Expt Therapeut, Hlth Sci Ctr, Coll Med, Bryan, TX 77807 USA.
RP Buonanno, A (reprint author), Eunice Shriver Kennedy Natl Inst Child Hlth & Hum, Sect Mol Neurobiol, Bethesda, MD 20892 USA.
EM buonanno@mail.nih.gov
RI Andersson, Richard/C-1579-2013
OI Andersson, Richard/0000-0003-1108-8397
FU Karolinska Institute doctoral fellowship; Karolinska Institute/National
Institutes of Health Graduate Partnerships Program; grants from the
Swedish Research Council (Vetenskapsradet); Swedish Brain Fund
(Hjarnfonden); Strategic Program in Neurosciences at Karolinska
Institute (StratNeuro); Swedish Medical Association (Svenska
Lakaresallskapet); Karolinska Institute; NICHD Intramural Research
Program
FX We thank V. Schram (National Institute of Child Health and Human
Development) and C. Smith (National Institute of Neurological Disorders
and Stroke) for assistance at the microscopy cores, and Joerg Neddens
for constructive comments. This work was supported by a Karolinska
Institute doctoral fellowship (R.H.A.), the Karolinska
Institute/National Institutes of Health Graduate Partnerships Program
(A.J.), and grants from the Swedish Research Council (Vetenskapsradet),
the Swedish Brain Fund (Hjarnfonden), the Strategic Program in
Neurosciences at Karolinska Institute (StratNeuro), the Swedish Medical
Association (Svenska Lakaresallskapet), and the Karolinska Institute
(A.F.), and the NICHD Intramural Research Program (P.A.H., I.K., D.V.,
and A.B.).
NR 48
TC 22
Z9 22
U1 2
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 7
PY 2012
VL 109
IS 32
BP 13118
EP 13123
DI 10.1073/pnas.1201011109
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 989HU
UT WOS:000307551700058
PM 22822214
ER
PT J
AU Liu, TY
Bian, X
Sun, S
Hu, XY
Klemm, RW
Prinz, WA
Rapoport, TA
Hu, JJ
AF Liu, Tina Y.
Bian, Xin
Sun, Sha
Hu, Xiaoyu
Klemm, Robin W.
Prinz, William A.
Rapoport, Tom A.
Hu, Junjie
TI Lipid interaction of the C terminus and association of the transmembrane
segments facilitate atlastin-mediated homotypic endoplasmic reticulum
fusion
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE membrane perturbation; content mixing; organelle shaping; organelle
remodeling; hereditary spastic paraplegia
ID HEREDITARY SPASTIC PARAPLEGIA; INFLUENZA-VIRUS HEMAGGLUTININ;
MEMBRANE-SPANNING DOMAIN; AMINO-ACID-SEQUENCE; MITOCHONDRIAL FUSION;
CYTOPLASMIC DOMAINS; STRUCTURAL BASIS; GOLGI-APPARATUS; GTPASE ATLASTIN;
G-PROTEIN
AB The homotypic fusion of endoplasmic reticulum (ER) membranes is mediated by atlastin (ATL), which consists of an N-terminal cytosolic domain containing a GTPase module and a three-helix bundle followed by two transmembrane (TM) segments and a C-terminal tail (CT). Fusion depends on a GTP hydrolysis-induced conformational change in the cytosolic domain. Here, we show that the CT and TM segments also are required for efficient fusion and provide insight into their mechanistic roles. The essential feature of the CT is a conserved amphipathic helix. A synthetic peptide corresponding to the helix, but not to unrelated amphipathic helices, can act in trans to restore the fusion activity of tailless ATL. The CT promotes vesicle fusion by interacting directly with and perturbing the lipid bilayer without causing significant lysis. The TM segments do not serve as mere membrane anchors for the cytosolic domain but rather mediate the formation of ATL oligomers. Point mutations in either the C-terminal helix or the TMs impair ATL's ability to generate and maintain ER morphology in vivo. Our results suggest that protein-lipid and protein-protein interactions within the membrane cooperate with the conformational change of the cytosolic domain to achieve homotypic ER membrane fusion.
C1 [Bian, Xin; Sun, Sha; Hu, Xiaoyu; Hu, Junjie] Nankai Univ, Coll Life Sci, Dept Genet & Cell Biol, Tianjin 300071, Peoples R China.
[Bian, Xin; Sun, Sha; Hu, Xiaoyu; Hu, Junjie] Tianjin Key Lab Prot Sci, Tianjin 300071, Peoples R China.
[Liu, Tina Y.; Klemm, Robin W.; Rapoport, Tom A.] Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA.
[Liu, Tina Y.; Klemm, Robin W.; Rapoport, Tom A.] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA.
[Prinz, William A.] NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Hu, JJ (reprint author), Nankai Univ, Coll Life Sci, Dept Genet & Cell Biol, Tianjin 300071, Peoples R China.
EM huj@nankai.edu.cn
RI Hu, Junjie/F-9713-2013; Klemm, Robin/C-5463-2014
OI Klemm, Robin/0000-0003-2313-8240
FU European Molecular Biology Organization Long-Term Fellowship; National
Institute of Diabetes and Digestive and Kidney Diseases intramural
program; National Basic Research Program of China 973 Program
[2010CB83370]; National Science Foundation of China Grant [3097144];
International Early Career Scientist grant from the Howard Hughes
Medical Institute; National Science Foundation
FX We thank A. Stein for helpful suggestions and R. King and A. Stein for
critical reading of the manuscript. T.Y.L. is supported by a fellowship
from the National Science Foundation, and R.W.K is supported by a
European Molecular Biology Organization Long-Term Fellowship. W.A.P. is
supported by the National Institute of Diabetes and Digestive and Kidney
Diseases intramural program. T.A.R. is a Howard Hughes Medical Institute
investigator. J.H. is supported by National Basic Research Program of
China 973 Program, Grant 2010CB83370; National Science Foundation of
China Grant 3097144; and an International Early Career Scientist grant
from the Howard Hughes Medical Institute.
NR 47
TC 38
Z9 38
U1 0
U2 10
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 7
PY 2012
VL 109
IS 32
BP E2146
EP E2154
DI 10.1073/pnas.1208385109
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 989HU
UT WOS:000307551700003
PM 22802620
ER
PT J
AU Capo-Ramos, DE
Gao, Y
Lubin, JH
Check, DP
Goldin, LR
Pesatori, AC
Consonni, D
Bertazzi, PA
Saxon, AJ
Bergen, AW
Caporaso, NE
Landi, MT
AF Capo-Ramos, David E.
Gao, Ying
Lubin, Jay H.
Check, David P.
Goldin, Lynn R.
Pesatori, Angela C.
Consonni, Dario
Bertazzi, Pier Alberto
Saxon, Andrew J.
Bergen, Andrew W.
Caporaso, Neil E.
Landi, Maria Teresa
TI Mood Disorders and Risk of Lung Cancer in the EAGLE Case-Control Study
and in the US Veterans Affairs Inpatient Cohort
SO PLOS ONE
LA English
DT Article
ID BIPOLAR DISORDER; MAJOR DEPRESSION; RECORD-LINKAGE; SEROTONIN; GENETICS;
SMOKING; ANTIDEPRESSANTS; SCHIZOPHRENIA; ENVIRONMENT; POPULATION
AB Background: Mood disorders may affect lung cancer risk. We evaluated this hypothesis in two large studies.
Methodology/Principal Findings: We examined 1,939 lung cancer cases and 2,102 controls from the Environment And Genetics in Lung cancer Etiology (EAGLE) case-control study conducted in Italy (2002-2005), and 82,945 inpatients with a lung cancer diagnosis and 3,586,299 person-years without a lung cancer diagnosis in the U. S. Veterans Affairs Inpatient Cohort (VA study), composed of veterans with a VA hospital admission (1969-1996). In EAGLE, we calculated odds ratios (ORs) and 95% confidence intervals (CI), with extensive adjustment for tobacco smoking and multiple lifestyle factors. In the VA study, we estimated lung cancer relative risks (RRs) and 95% CIs with time-dependent Poisson regression, adjusting for attained age, calendar year, hospital visits, time within the study, and related previous medical diagnoses. In EAGLE, we found decreased lung cancer risk in subjects with a personal history of mood disorders (OR: 0.59, 95% CI: 0.44-0.79, based on 121 lung cancer incident cases and 192 controls) and family history of mood disorders (OR: 0.62, 95% CI: 0.50-0.77, based on 223 lung cancer cases and 345 controls). The VA study analyses yielded similar results (RR: 0.74, 95% CI: 0.71-0.77, based on 2,304 incident lung cancer cases and 177,267 non-cancer person-years) in men with discharge diagnoses for mood disorders. History of mood disorders was associated with nicotine dependence, alcohol and substance use and psychometric scales of depressive and anxiety symptoms in controls for these studies.
Conclusions/Significance: The consistent finding of a relationship between mood disorders and lung cancer risk across two large studies calls for further research into the complex interplay of risk factors associated with these two widespread and debilitating diseases. Although we adjusted for smoking effects in EAGLE, residual confounding of the results by smoking cannot be ruled out.
C1 [Capo-Ramos, David E.; Gao, Ying; Lubin, Jay H.; Check, David P.; Goldin, Lynn R.; Caporaso, Neil E.; Landi, Maria Teresa] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Pesatori, Angela C.; Consonni, Dario; Bertazzi, Pier Alberto] Univ Milan, Epidemiol Res Ctr, EPOCA, Milan, Italy.
[Pesatori, Angela C.; Consonni, Dario; Bertazzi, Pier Alberto] Fdn IRCCS Ca Granda Osped Maggiore Policlin, Epidemiol Unit, Milan, Italy.
[Saxon, Andrew J.] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA.
[Saxon, Andrew J.] Addict Psychiat Residency Program, Seattle, WA USA.
[Saxon, Andrew J.] Univ Washington, Seattle, WA 98195 USA.
[Bergen, Andrew W.] SRI Int, Ctr Hlth Sci, Mol Genet Program, Menlo Pk, CA 94025 USA.
RP Capo-Ramos, DE (reprint author), Ctr Dis Control & Prevent, Off Anal & Epidemiol, Natl Ctr Hlth Stat, Hyattsville, MD 20782 USA.
EM landim@mail.nih.gov
RI Consonni, Dario/K-7943-2016; bertazzi, pietro alberto/D-5039-2017;
OI Consonni, Dario/0000-0002-8935-3843; bertazzi, pietro
alberto/0000-0003-3475-2449; pesatori, angela/0000-0002-0261-3252;
Bergen, Andrew/0000-0002-1237-7644
FU National Institutes of Health, National Cancer Institute (Division of
Cancer Epidemiology and Genetics); Region of Lombardy, Milan, Italy
(Environmental Epidemiology Program); Center of Excellence in Substance
Abuse Treatment and Education at VA Puget Sound Health Care System; NIH
[U01DA020830, RC2DA028793]
FX Funding for this study was provided by the Intramural Research Program
of the National Institutes of Health, National Cancer Institute
(Division of Cancer Epidemiology and Genetics) and by the Region of
Lombardy, Milan, Italy (Environmental Epidemiology Program). Dr. Saxon
is supported by the Center of Excellence in Substance Abuse Treatment
and Education at VA Puget Sound Health Care System. Dr. Bergen is
supported by NIH grants U01DA020830 and RC2DA028793. The funders had no
role in study design, data collection and analysis, decision to publish,
or preparation of the manuscript.
NR 44
TC 1
Z9 1
U1 0
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 7
PY 2012
VL 7
IS 8
AR e42945
DI 10.1371/journal.pone.0042945
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 987SL
UT WOS:000307437900063
PM 22880133
ER
PT J
AU Gong, R
Wang, YP
Ying, TL
Dimitrov, DS
AF Gong, Rui
Wang, Yanping
Ying, Tianlei
Dimitrov, Dimiter S.
TI Bispecific Engineered Antibody Domains (Nanoantibodies) That Interact
Noncompetitively with an HIV-1 Neutralizing Epitope and FcRn
SO PLOS ONE
LA English
DT Article
ID INTERNATIONAL IMMUNOGENETICS DATABASE; BINDING-SITE; CH2 DOMAINS; HUMAN
IGG1; THERAPEUTIC ANTIBODIES; MOLECULAR RECOGNITION;
INCREASED-STABILITY; PROTEIN SCAFFOLDS; CRYSTAL-STRUCTURE; RECEPTOR
AB Libraries based on an isolated human immunoglobulin G1 (IgG1) constant domain 2 (CH2) have been previously diversified by random mutagenesis. However, native isolated CH2 is not very stable and the generation of many mutations could lead to an increase in immunogenicity. Recently, we demonstrated that engineering an additional disulfide bond and removing seven N-terminal residues results in an engineered antibody domain (eAd) (m01s) with highly increased stability and enhanced binding to human neonatal Fc receptor (FcRn) (Gong et al, JBC, 2009 and 2011). We and others have also previously shown that grafting of the heavy chain complementarity region 3 (CDR-H3 (H3)) onto cognate positions of the variable domain leads to highly diversified libraries from which a number of binders to various antigens have been selected. However, grafting of H3s to non-cognate positions in constant domains results in additional residues at the junctions of H3s and the CH2 framework. Here we describe a new method based on multi-step PCR that allows the precise replacement of loop FG (no changes in its flanking sequences) by human H3s from another library. Using this method and limited mutagenesis of loops BC and DE we generated an eAd phage-displayed library. Panning of this library against an HIV-1 gp41 MPER peptide resulted in selection of a binder, m2a1, which neutralized HIV-1 isolates from different clades with modest activity and retained the m01s capability of binding to FcRn. This result provides a proof of concept that CH2-based antigen binders that also mimic to certain extent other functions of full-size antibodies (binding to FcRn) can be generated; we have previously hypothesized that such binders can be made and coined the term nanoantibodies (nAbs). Further studies in animal models and in humans will show how useful nAbs could be as therapeutics and diagnostics.
C1 [Gong, Rui; Wang, Yanping; Ying, Tianlei; Dimitrov, Dimiter S.] NIH, Prot Interact Grp, Frederick Natl Lab Canc Res, Frederick, MD USA.
[Wang, Yanping] SAIC Frederick Inc, Frederick, MD USA.
RP Gong, R (reprint author), NIH, Prot Interact Grp, Frederick Natl Lab Canc Res, Frederick, MD USA.
EM gongr@mail.nih.gov
FU National Institutes of Health (NIH); NIH, National Cancer Institute
(NCI), Center for Cancer Research; NCI, NIH [N01-CO-12400]; U.S.
Government
FX This work was supported by the Intramural AIDS Targeted Antiviral
Program (IATAP), National Institutes of Health (NIH) to DSD, and by the
Intramural Research Program of the NIH, National Cancer Institute (NCI),
Center for Cancer Research. This project has been funded in whole or in
part with federal funds from the NCI, NIH, under contract N01-CO-12400.
The funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.; SAIC-Frederick,
Inc. is a wholly owned subsidiary of Science Applications International
Corporation and operates exclusively under a single, long-term contract
to the National Cancer Institute, part of the U.S. National Institutes
of Health. All funding is derived from the U.S. Government. This does
not alter the authors' adherence to all the PLoS ONE policies on sharing
data and materials.
NR 54
TC 8
Z9 9
U1 1
U2 8
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 7
PY 2012
VL 7
IS 8
AR e42288
DI 10.1371/journal.pone.0042288
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 987SL
UT WOS:000307437900027
PM 22879932
ER
PT J
AU Hein, R
Maranian, M
Hopper, JL
Kapuscinski, MK
Southey, MC
Park, DJ
Schmidt, MK
Broeks, A
Hogervorst, FBL
Bueno-de-Mesquit, HB
Muir, KR
Lophatananon, A
Rattanamongkongul, S
Puttawibul, P
Fasching, PA
Hein, A
Ekici, AB
Beckmann, MW
Fletcher, O
Johnson, N
Silva, ID
Peto, J
Sawyer, E
Tomlinson, I
Kerin, M
Miller, N
Marmee, F
Schneeweiss, A
Sohn, C
Burwinkel, B
Guenel, P
Cordina-Duverger, E
Menegaux, F
Truong, T
Bojesen, SE
Nordestgaard, BG
Flyger, H
Milne, RL
Perez, JIA
Zamora, MP
Benitez, J
Anton-Culver, H
Ziogas, A
Bernstein, L
Clarke, CA
Brenner, H
Muller, H
Arndt, V
Stegmaier, C
Rahman, N
Seal, S
Turnbull, C
Renwick, A
Meindl, A
Schott, S
Bartram, CR
Schmutzler, RK
Brauch, H
Hamann, U
Ko, YD
Wang-Gohrke, S
Dork, T
Schurmann, P
Karstens, JH
Hillemanns, P
Nevanlinna, H
Heikkinen, T
Aittomaki, K
Blomqvist, C
Bogdanova, NV
Zalutsky, IV
Antonenkova, NN
Bermisheva, M
Prokovieva, D
Farahtdinova, A
Khusnutdinova, E
Lindblom, A
Margolin, S
Mannermaa, A
Kataja, V
Kosma, VM
Hartikainen, J
Chen, XQ
Beesley, J
Lambrechts, D
Zhao, H
Neven, P
Wildiers, H
Nickels, S
Flesch-Janys, D
Radice, P
Peterlongo, P
Manoukian, S
Barile, M
Couch, FJ
Olson, JE
Wang, XS
Fredericksen, Z
Giles, GG
Baglietto, L
McLean, CA
Severi, G
Offit, K
Robson, M
Gaudet, MM
Vijai, J
Alnaes, GG
Kristensen, V
Borresen-Dale, AL
John, EM
Miron, A
Winqvist, R
Pylkas, K
Jukkola-Vuorinen, A
Grip, M
Andrulis, IL
Knight, JA
Glendon, G
Mulligan, AM
Figueroa, JD
Garcia-Closas, M
Lissowska, J
Sherman, ME
Hooning, M
Martens, JWM
Seynaeve, C
Collee, M
Hall, P
Humpreys, K
Czene, K
Liu, JJ
Cox, A
Brock, IW
Cross, SS
Reed, MWR
Ahmed, S
Ghoussaini, M
Pharoah, PDP
Kang, D
Yoo, KY
Noh, DY
Jakubowska, A
Jaworska, K
Durda, K
Zlowocka, E
Sangrajrang, S
Gaborieau, V
Brennan, P
McKay, J
Shen, CY
Yu, JC
Hsu, HM
Hou, MF
Orr, N
Schoemaker, M
Ashworth, A
Swerdlow, A
Trentham-Dietz, A
Newcomb, PA
Titus, L
Egan, KM
Chenevix-Trench, G
Antoniou, AC
Humphreys, MK
Morrison, J
Chang-Claude, J
Easton, DF
Dunning, AM
AF Hein, Rebecca
Maranian, Melanie
Hopper, John L.
Kapuscinski, Miroslaw K.
Southey, Melissa C.
Park, Daniel J.
Schmidt, Marjanka K.
Broeks, Annegien
Hogervorst, Frans B. L.
Bueno-de-Mesquit, H. Bas
Muir, Kenneth R.
Lophatananon, Artitaya
Rattanamongkongul, Suthee
Puttawibul, Puttisak
Fasching, Peter A.
Hein, Alexander
Ekici, Arif B.
Beckmann, Matthias W.
Fletcher, Olivia
Johnson, Nichola
Silva, Isabel dos Santos
Peto, Julian
Sawyer, Elinor
Tomlinson, Ian
Kerin, Michael
Miller, Nicola
Marmee, Frederick
Schneeweiss, Andreas
Sohn, Christof
Burwinkel, Barbara
Guenel, Pascal
Cordina-Duverger, Emilie
Menegaux, Florence
Truong, Therese
Bojesen, Stig E.
Nordestgaard, Borge G.
Flyger, Henrik
Milne, Roger L.
Arias Perez, Jose Ignacio
Pilar Zamora, M.
Benitez, Javier
Anton-Culver, Hoda
Ziogas, Argyrios
Bernstein, Leslie
Clarke, Christina A.
Brenner, Hermann
Mueller, Heiko
Arndt, Volker
Stegmaier, Christa
Rahman, Nazneen
Seal, Sheila
Turnbull, Clare
Renwick, Anthony
Meindl, Alfons
Schott, Sarah
Bartram, Claus R.
Schmutzler, Rita K.
Brauch, Hiltrud
Hamann, Ute
Ko, Yon-Dschun
Wang-Gohrke, Shan
Doerk, Thilo
Schuermann, Peter
Karstens, Johann H.
Hillemanns, Peter
Nevanlinna, Heli
Heikkinen, Tuomas
Aittomaki, Kristiina
Blomqvist, Carl
Bogdanova, Natalia V.
Zalutsky, Iosif V.
Antonenkova, Natalia N.
Bermisheva, Marina
Prokovieva, Darya
Farahtdinova, Albina
Khusnutdinova, Elza
Lindblom, Annika
Margolin, Sara
Mannermaa, Arto
Kataja, Vesa
Kosma, Veli-Matti
Hartikainen, Jaana
Chen, Xiaoqing
Beesley, Jonathan
Lambrechts, Diether
Zhao, Hui
Neven, Patrick
Wildiers, Hans
Nickels, Stefan
Flesch-Janys, Dieter
Radice, Paolo
Peterlongo, Paolo
Manoukian, Siranoush
Barile, Monica
Couch, Fergus J.
Olson, Janet E.
Wang, Xianshu
Fredericksen, Zachary
Giles, Graham G.
Baglietto, Laura
McLean, Catriona A.
Severi, Gianluca
Offit, Kenneth
Robson, Mark
Gaudet, Mia M.
Vijai, Joseph
Alnaes, Grethe Grenaker
Kristensen, Vessela
Borresen-Dale, Anne-Lise
John, Esther M.
Miron, Alexander
Winqvist, Robert
Pylkas, Katri
Jukkola-Vuorinen, Arja
Grip, Mervi
Andrulis, Irene L.
Knight, Julia A.
Glendon, Gord
Mulligan, Anna Marie
Figueroa, Jonine D.
Garcia-Closas, Montserrat
Lissowska, Jolanta
Sherman, Mark E.
Hooning, Maartje
Martens, John W. M.
Seynaeve, Caroline
Collee, Margriet
Hall, Per
Humpreys, Keith
Czene, Kamila
Liu, Jianjun
Cox, Angela
Brock, Ian W.
Cross, Simon S.
Reed, Malcolm W. R.
Ahmed, Shahana
Ghoussaini, Maya
Pharoah, Paul D. P.
Kang, Daehee
Yoo, Keun-Young
Noh, Dong-Young
Jakubowska, Anna
Jaworska, Katarzyna
Durda, Katarzyna
Zlowocka, Elzbieta
Sangrajrang, Suleeporn
Gaborieau, Valerie
Brennan, Paul
McKay, James
Shen, Chen-Yang
Yu, Jyh-Cherng
Hsu, Huan-Ming
Hou, Ming-Feng
Orr, Nick
Schoemaker, Minouk
Ashworth, Alan
Swerdlow, Anthony
Trentham-Dietz, Amy
Newcomb, Polly A.
Titus, Linda
Egan, Kathleen M.
Chenevix-Trench, Georgia
Antoniou, Antonis C.
Humphreys, Manjeet K.
Morrison, Jonathan
Chang-Claude, Jenny
Easton, Douglas F.
Dunning, Alison M.
CA GENICA Network
kConFab Investigators
AOCS Grp
TI Comparison of 6q25 Breast Cancer Hits from Asian and European Genome
Wide Association Studies in the Breast Cancer Association Consortium
(BCAC)
SO PLOS ONE
LA English
DT Article
ID SUSCEPTIBILITY LOCUS; CHINESE; WOMEN
AB The 6q25.1 locus was first identified via a genome-wide association study (GWAS) in Chinese women and marked by single nucleotide polymorphism (SNP) rs2046210, approximately 180 Kb upstream of ESR1. There have been conflicting reports about the association of this locus with breast cancer in Europeans, and a GWAS in Europeans identified a different SNP, tagged here by rs12662670. We examined the associations of both SNPs in up to 61,689 cases and 58,822 controls from forty-four studies collaborating in the Breast Cancer Association Consortium, of which four studies were of Asian and 39 of European descent. Logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI). Case-only analyses were used to compare SNP effects in Estrogen Receptor positive (ER+) versus negative (ER-) tumours. Models including both SNPs were fitted to investigate whether the SNP effects were independent. Both SNPs are significantly associated with breast cancer risk in both ethnic groups. Per-allele ORs are higher in Asian than in European studies [rs2046210: OR (A/G) = 1.36 (95% CI 1.26-1.48), p = 7.6x10(-14) in Asians and 1.09 (95% CI 1.07-1.11), p = 6.8x10(-18) in Europeans. rs12662670: OR (G/T) = 1.29 (95% CI 1.19-1.41), p = 1.2x10(-9) in Asians and 1.12 (95% CI 1.08-1.17), p = 3.8x10(-9) in Europeans]. SNP rs2046210 is associated with a significantly greater risk of ER- than ER+ tumours in Europeans [OR (ER-) = 1.20 (95% CI 1.15-1.25), p = 1.8x10(-17) versus OR (ER+) = 1.07 (95% CI 1.04-1.1), p = 1.3x10(-7), p(heterogeneity) = 5.1x10(-6)]. In these Asian studies, by contrast, there is no clear evidence of a differential association by tumour receptor status. Each SNP is associated with risk after adjustment for the other SNP. These results suggest the presence of two variants at 6q25.1 each independently associated with breast cancer risk in Asians and in Europeans. Of these two, the one tagged by rs2046210 is associated with a greater risk of ER- tumours.
C1 [Hein, Rebecca; Nickels, Stefan; Chang-Claude, Jenny] German Canc Res Ctr, Unit Genet Epidemiol, Div Canc Epidemiol, Heidelberg, Germany.
[Hein, Rebecca] Univ Cologne, PMV Primarmed Versorgung Res Grp, Dept Child & Adolescent Psychiat & Psychotherapy, D-50931 Cologne, Germany.
[Maranian, Melanie; Ahmed, Shahana; Ghoussaini, Maya; Pharoah, Paul D. P.; Dunning, Alison M.] Univ Cambridge, Dept Oncol, Cambridge, England.
[Hopper, John L.; Kapuscinski, Miroslaw K.; Giles, Graham G.; Baglietto, Laura; Severi, Gianluca] Univ Melbourne, Ctr Mol Environm Genet & Analyt Epidemiol, Melbourne, Vic, Australia.
[Park, Daniel J.] Univ Melbourne, Dept Pathol, Genet Epidemiol Lab, Melbourne, Vic, Australia.
[Hogervorst, Frans B. L.] Antoni Van Leeuwenhoek Hosp, Netherlands Canc Inst, Family Canc Clin, Amsterdam, Netherlands.
[Bueno-de-Mesquit, H. Bas] Natl Inst Publ Hlth & Environm, NL-3720 BA Bilthoven, Netherlands.
[Muir, Kenneth R.; Lophatananon, Artitaya] Univ Warwick, Hlth Sci Res Inst, Warwick Med Sch, Warwick, England.
[Rattanamongkongul, Suthee] Srinakhrainwirot Univ, Dept Prevent Med, Ongkharak, Nakhon Nayok, Thailand.
[Puttawibul, Puttisak] Prince Songkla Univ, Sch Med, Dept Surg, Hat Yai, Thailand.
[Fasching, Peter A.; Hein, Alexander; Beckmann, Matthias W.] Univ Hosp Erlangen, Univ Breast Ctr, Dept Gynecol & Obstet, Erlangen, Germany.
[Fasching, Peter A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Hematol & Oncol, Los Angeles, CA 90095 USA.
[Ekici, Arif B.] Univ Erlangen Nurnberg, Inst Human Genet, Erlangen, Germany.
[Fletcher, Olivia; Johnson, Nichola; Garcia-Closas, Montserrat; Orr, Nick; Ashworth, Alan] Inst Canc Res, Breakthrough Breast Canc Res Ctr, London SW3 6JB, England.
[Silva, Isabel dos Santos; Peto, Julian] London Sch Hyg & Trop Med, Dept Noncommunicable Dis Epidemiol, London WC1, England.
[Sawyer, Elinor] Kings Coll London, Natl Inst Hlth Res, Guys & St Thomas Natl Hlth Serv Fdn Trust, Div Canc Studies,Comprehens Biomed Res Ctr, London WC2R 2LS, England.
[Tomlinson, Ian] Univ Oxford, Welcome Trust Ctr Human Genet, Oxford, England.
[Tomlinson, Ian] Univ Oxford, Oxford Biomed Res Ctr, Oxford, England.
[Tomlinson, Ian] Oxford Natl Inst Hlth Res, Comprehens Biomed Res Ctr, Oxford, England.
[Kerin, Michael] Univ Hosp Galway, Inst Clin Sci, Galway, Ireland.
[Miller, Nicola; Marmee, Frederick; Schneeweiss, Andreas; Sohn, Christof; Burwinkel, Barbara; Schott, Sarah] Univ Heidelberg, Dept Obstet & Gynecol, Heidelberg, Germany.
[Marmee, Frederick; Schneeweiss, Andreas] Univ Heidelberg, Natl Ctr Tumor Dis, Heidelberg, Germany.
[Burwinkel, Barbara] German Canc Res Ctr, Mol Epidemiol Grp, Heidelberg, Germany.
[Guenel, Pascal; Cordina-Duverger, Emilie; Menegaux, Florence; Truong, Therese] Inserm Natl Inst Hlth & Med Res, U1018, CESP Ctr Res Epidemiol & Populat Hlth, Villejuif, France.
[Guenel, Pascal; Cordina-Duverger, Emilie; Menegaux, Florence; Truong, Therese] Univ Paris 11, Unite Mixte Rech 1018, Villejuif, France.
[Bojesen, Stig E.; Nordestgaard, Borge G.] Univ Copenhagen, Copenhagen Gen Populat Study, Herlev Univ Hosp, Copenhagen, Denmark.
[Bojesen, Stig E.; Nordestgaard, Borge G.] Univ Copenhagen, Dept Clin Biochem, Herlev Univ Hosp, Copenhagen, Denmark.
[Flyger, Henrik] Univ Copenhagen, Dept Breast Surg, Herlev Univ Hosp, Copenhagen, Denmark.
[Milne, Roger L.] Spanish Natl Canc Res Ctr CNIO, Genet & Mol Epidemiol Grp, Madrid, Spain.
[Arias Perez, Jose Ignacio] Hosp Monte Naranco, Serv Cirugia Gen & Especialidades, Oviedo, Spain.
[Pilar Zamora, M.] Hosp Univ La Paz, Serv Oncol Med, Madrid, Spain.
[Benitez, Javier] Spanish Natl Canc Res Ctr CNIO, Canc Genet Grp, Madrid, Spain.
[Anton-Culver, Hoda; Ziogas, Argyrios] Univ Calif Irvine, Dept Epidemiol, Irvine, CA USA.
[Bernstein, Leslie] City Hope Natl Med Ctr, Dept Populat Sci, Duarte, CA USA.
[Brenner, Hermann; Mueller, Heiko; Arndt, Volker] German Canc Res Ctr, Div Clin Epidemiol & Aging Res, D-6900 Heidelberg, Germany.
[Stegmaier, Christa] Saarland Canc Registry, Saarbrucken, Germany.
[Rahman, Nazneen; Seal, Sheila; Turnbull, Clare; Renwick, Anthony] Inst Canc Res, Sect Canc Genet, Sutton, Surrey, England.
[Meindl, Alfons] Tech Univ Munich, Klinikum Rechts Isar, Div Obstet & Gynecol, D-8000 Munich, Germany.
[Schmutzler, Rita K.] Univ Hosp, Ctr Familial Breast & Ovarian Canc, Cologne, Germany.
[Schmutzler, Rita K.] Univ Hosp, CIO, Cologne, Germany.
[Bartram, Claus R.] Univ Heidelberg, Inst Human Genet, Heidelberg, Germany.
[Brauch, Hiltrud] Univ Tubingen, Dr Margarete Fischer Bosch Inst Clin Pharmacol, Tubingen, Germany.
[Hamann, Ute] Deutsch Krebsforschungszentrum DKFZ, Heidelberg, Germany.
[Ko, Yon-Dschun] Evangel Kliniken Bonn gGmbH, Johanniter Krankenhaus, Dept Internal Med, Bonn, Germany.
Univ Bonn, Inst Pathol, Bonn, Germany.
[GENICA Network] Inst Prevent & Occupat Med German Social Accid In, Bochum, Germany.
[Wang-Gohrke, Shan] Univ Ulm, Dept Obstet & Gynecol, Ulm, Germany.
[Doerk, Thilo; Schuermann, Peter; Hillemanns, Peter; Bogdanova, Natalia V.] Hannover Med Sch, Clin Obstet, D-3000 Hannover, Germany.
[Doerk, Thilo; Schuermann, Peter; Hillemanns, Peter; Bogdanova, Natalia V.] Hannover Med Sch, Clin Gynaecol, D-3000 Hannover, Germany.
[Karstens, Johann H.; Bogdanova, Natalia V.; Mannermaa, Arto] Hannover Med Sch, Clin Radiat Oncol, D-3000 Hannover, Germany.
[Nevanlinna, Heli; Heikkinen, Tuomas] Univ Helsinki, Dept Obstet & Gynecol, Helsinki, Finland.
[Aittomaki, Kristiina] Univ Helsinki, Cent Hosp, Dept Clin Genet, Helsinki, Finland.
[Blomqvist, Carl] Univ Helsinki, Cent Hosp, Dept Oncol, Helsinki, Finland.
[Zalutsky, Iosif V.; Antonenkova, Natalia N.] NN Alexandrov Res Inst Oncol & Med Radiol, Minsk, Byelarus.
[Bermisheva, Marina; Prokovieva, Darya; Farahtdinova, Albina; Khusnutdinova, Elza] Russian Acad Sci, Inst Biochem & Genet, Ufa Sci Ctr, Ufa 450001, Russia.
[Lindblom, Annika] Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden.
[Margolin, Sara; Mannermaa, Arto] Karolinska Inst, Dept Oncol Pathol, Stockholm, Sweden.
[Kosma, Veli-Matti; Hartikainen, Jaana] Univ Eastern Finland, Sch Med, Inst Clin Med Pathol & Forens Med, Kuopio, Finland.
[Mannermaa, Arto; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, Jaana] Kuopio Univ Hosp, Bioctr Kuopio, SF-70210 Kuopio, Finland.
[Mannermaa, Arto; Kosma, Veli-Matti; Hartikainen, Jaana] Kuopio Univ Hosp, Dept Clin Pathol, SF-70210 Kuopio, Finland.
[Kataja, Vesa] Univ Eastern Finland, Sch Med, Inst Clin Med, Kuopio, Finland.
[Kataja, Vesa] Kuopio Univ Hosp, Dept Oncol, SF-70210 Kuopio, Finland.
[Chen, Xiaoqing; Beesley, Jonathan; Chenevix-Trench, Georgia] Queensland Inst Med Res, Canc Div, Brisbane, Qld 4006, Australia.
[kConFab Investigators] Peter MacCallum Canc Ctr, Kathleen Cuningham Fdn Consortium Res Familial Br, Melbourne, Vic, Australia.
[AOCS Grp] Peter MacCallum Canc Ctr, AOCS, Melbourne, Vic, Australia.
[Lambrechts, Diether; Zhao, Hui] Katholieke Univ KU Leuven, Vesalius Res Ctr, Louvain, Belgium.
[Neven, Patrick; Wildiers, Hans] Univ Hosp Gasthuisberg, Multidisciplinary Breast Ctr, B-3000 Louvain, Belgium.
[Flesch-Janys, Dieter] Univ Clin Hamburg Eppendorf, Dept Canc Epidemiol, Clin Canc Registry, Hamburg, Germany.
[Flesch-Janys, Dieter] Univ Clin Hamburg Eppendorf, Inst Med Biometr & Epidemiol, Hamburg, Germany.
[Radice, Paolo; Peterlongo, Paolo] Fdn IRCCS Ist Nazl Tumori INT, Unit Mol Bases Genet Risk & Genet Testing, Dept Prevent & Predict Med, Milan, Italy.
[Radice, Paolo; Peterlongo, Paolo] Fdn Ist FIRC Fdn Italiana Ric Canc Oncol Mol IFOM, Milan, Italy.
[Manoukian, Siranoush] Fdn Inst Recuvero & Cura Carattere Sci IRCCS Ist, Unit Med Genet, Dept Prevent & Predict Med, Milan, Italy.
[Barile, Monica] Ist Europeo Oncol, Div Canc Prevent & Genet, Milan, Italy.
[Couch, Fergus J.; Olson, Janet E.; Fredericksen, Zachary] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA.
[Wang, Xianshu] Mayo Clin, Dept Hlth Sci Res, Rochester, MN USA.
[Giles, Graham G.; Baglietto, Laura; Severi, Gianluca] Canc Council Victoria, Canc Epidemiol Ctr, Melbourne, Vic, Australia.
[McLean, Catriona A.] Alfred Hosp, Dept Anat Pathol, Melbourne, Vic, Australia.
[Offit, Kenneth; Vijai, Joseph] Mem Sloan Kettering Canc Ctr, Clin Genet Serv, Dept Med & Canc Biol & Genet, New York, NY 10021 USA.
[Robson, Mark] Mem Sloan Kettering Canc Ctr, Dept Med, Clin Genet Serv, New York, NY 10021 USA.
[Gaudet, Mia M.] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA.
[Alnaes, Grethe Grenaker; Kristensen, Vessela; Borresen-Dale, Anne-Lise] Radiumhosp, Oslo Univ Hosp, Dept Genet, Inst Canc Res, Oslo, Norway.
[Kristensen, Vessela; Borresen-Dale, Anne-Lise] Univ Oslo, Fac Med, Fac Div Ahus, Oslo, Norway.
[John, Esther M.] Canc Prevent Inst Calif, Dept Epidemiol, Fremont, CA USA.
[John, Esther M.] Stanford Univ, Sch Med, Stanford, CA 94305 USA.
[Miron, Alexander] Dana Farber Canc Inst, Deptartment Canc Biol, Boston, MA 02115 USA.
[Winqvist, Robert; Pylkas, Katri] Univ Oulu, Oulu Univ Hosp, Canc Genet Lab, Dept Clin Genet, Oulu, Finland.
[Winqvist, Robert; Pylkas, Katri] Univ Oulu, Oulu Univ Hosp, Bioctr Oulu, Oulu, Finland.
[Jukkola-Vuorinen, Arja] Univ Oulu, Oulu Univ Hosp, Dept Oncol, Oulu, Finland.
[Grip, Mervi] Univ Oulu, Dept Surg, Oulu Univ Hosp, Oulu, Finland.
[Andrulis, Irene L.; Glendon, Gord] Canc Care Ontario, Ontario Canc Genet Network, Toronto, ON, Canada.
[Andrulis, Irene L.] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Fred A Litwin Ctr Canc Genet, Toronto, ON M5G 1X5, Canada.
[Andrulis, Irene L.] Univ Toronto, Dept Mol Genet, Toronto, ON, Canada.
[Knight, Julia A.] Univ Toronto, Div Epidemiol, Dalla Lana Sch Publ Hlth, Toronto, ON, Canada.
[Mulligan, Anna Marie] Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON, Canada.
[Mulligan, Anna Marie] St Michaels Hosp, Dept Lab Med, Toronto, ON M5B 1W8, Canada.
[Mulligan, Anna Marie] St Michaels Hosp, Keenan Res Ctr, Li Ka Shing Knowledge Inst, Toronto, ON M5B 1W8, Canada.
[Figueroa, Jonine D.; Garcia-Closas, Montserrat; Sherman, Mark E.] Natl Canc Inst, Div Canc Epidemiol & Genet, Rockville, MD USA.
[Garcia-Closas, Montserrat] Inst Canc Res, Epidemiol Sect, London SW3 6JB, England.
[Garcia-Closas, Montserrat] Inst Canc Res, Genet Sect, London SW3 6JB, England.
[Lissowska, Jolanta] M Sklodowska Curie Mem Canc Ctr, Dept Canc Epidemiol & Prevent, Warsaw, Poland.
[Lissowska, Jolanta] Inst Oncol, Warsaw, Poland.
[Hooning, Maartje; Seynaeve, Caroline] Erasmus Univ, Med Ctr, Dept Med Oncol, Family Canc Clin, Rotterdam, Netherlands.
[Martens, John W. M.] Erasmus Univ, Med Ctr, Dept Med Oncol, Josephine Nefkens Inst, Rotterdam, Netherlands.
[Collee, Margriet] Erasmus Univ, Med Ctr, Dept Clin Genet, Family Canc Clin, Rotterdam, Netherlands.
[Hall, Per; Humpreys, Keith; Czene, Kamila] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
[Liu, Jianjun] Genome Inst Singapore, Singapore, Singapore.
[Cox, Angela; Brock, Ian W.] Univ Sheffield, Inst Canc Studies, Dept Oncol, Sheffield, S Yorkshire, England.
[Cross, Simon S.] Univ Sheffield, Acad Unit Pathol, Dept Neurosci, Sheffield, S Yorkshire, England.
[Reed, Malcolm W. R.] Univ Sheffield, Acad Unit Surg Oncol, Dept Oncol, Sheffield, S Yorkshire, England.
[Pharoah, Paul D. P.; Antoniou, Antonis C.; Humphreys, Manjeet K.; Morrison, Jonathan; Easton, Douglas F.] Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England.
[Kang, Daehee; Yoo, Keun-Young] Seoul Natl Univ, Coll Med, Dept Prevent Med, Seoul, South Korea.
[Noh, Dong-Young] Seoul Natl Univ, Coll Med, Dept Surg, Seoul, South Korea.
[Jakubowska, Anna; Jaworska, Katarzyna; Durda, Katarzyna; Zlowocka, Elzbieta] Pomeranian Med Univ, Dept Genet & Pathol, Szczecin, Poland.
[Jaworska, Katarzyna] Warsaw Med Univ, Postgrad Sch Mol Med, Warsaw, Poland.
[Sangrajrang, Suleeporn] Natl Canc Inst, Mol Epidemiol Unit, Bangkok, Thailand.
[Gaborieau, Valerie; Brennan, Paul; McKay, James] Int Agcy Res Canc, Genet Epidemiol Grp, F-69372 Lyon, France.
[Shen, Chen-Yang] Acad Sinica, Inst Biomed Sci, Taipei, Taiwan.
[Shen, Chen-Yang] Taiwan Biobank, Taipei, Taiwan.
[Yu, Jyh-Cherng; Hsu, Huan-Ming] Tri Serv Gen Hosp, Dept Surg, Taipei, Taiwan.
[Hou, Ming-Feng] Kaohsiung Med Univ, Chung Ho Mem Hosp, Ctr Canc, Kaohsiung, Taiwan.
[Hou, Ming-Feng] Kaohsiung Med Univ, Chung Ho Mem Hosp, Dept Surg, Kaohsiung, Taiwan.
[Schoemaker, Minouk; Swerdlow, Anthony] Inst Canc Res, Epidemiol Sect, Sutton, Surrey, England.
[Trentham-Dietz, Amy; Newcomb, Polly A.] Univ Wisconsin, Carbone Canc Ctr, Madison, WI USA.
[Newcomb, Polly A.] Fred Hutchinson Canc Res Ctr, Canc Prevent Program, Seattle, WA 98104 USA.
[Titus, Linda] Dartmouth Hitchcock Med Ctr, Dept Community & Family Med, Dept Pediat, Dartmouth Med Sch, Lebanon, NH 03766 USA.
[Egan, Kathleen M.] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Div Populat Sci, Tampa, FL 33612 USA.
RP Hein, R (reprint author), German Canc Res Ctr, Unit Genet Epidemiol, Div Canc Epidemiol, Heidelberg, Germany.
EM rebecca.hein@uk-koeln.de; alisond@srl.cam.ac.uk
RI Jakubowska, Anna/O-8050-2014; Gonzalez-Neira, Anna/C-5791-2015;
Garcia-Closas, Montserrat /F-3871-2015; Hartikainen, Jaana/E-6256-2015;
Bowtell, David/H-1007-2016; Bruning, Thomas/G-8120-2015; Khusnutdinova,
Elza/A-4810-2013; Brenner, Hermann/B-4627-2017; manoukian,
siranoush/E-7132-2017; Peissel, Bernard/E-8187-2017; Rahman,
Nazneen/D-2802-2013; Joseph, Vijai/J-9158-2013; Radice,
Paolo/O-3119-2013; Verdrengh, Evelien/H-4571-2012; Noh,
Dong-Young/G-5531-2011; Yoo, Keun-Young/J-5548-2012; truong,
therese/A-2837-2013; Kerin, Michael/D-6748-2013; Knight,
Julia/A-6843-2012; Dork, Thilo/J-8620-2012; Bernard, Loris/K-5953-2014;
Ekici, Arif/C-3971-2013; Hein, Alexander/F-6999-2010; Andrulis,
Irene/E-7267-2013
OI Czene, Kamila/0000-0002-3233-5695; Cross, Simon/0000-0003-2044-1754;
Lissowska, Jolanta/0000-0003-2695-5799; Dunning, Alison
Margaret/0000-0001-6651-7166; Nevanlinna, Heli/0000-0002-0916-2976; Cox,
Angela/0000-0002-5138-1099; Park, Daniel/0000-0002-6354-0931; Giles,
Graham/0000-0003-4946-9099; Garcia-Closas, Montserrat
/0000-0003-1033-2650; Bowtell, David/0000-0001-9089-7525; Bruning,
Thomas/0000-0001-9560-5464; Brenner, Hermann/0000-0002-6129-1572;
manoukian, siranoush/0000-0002-6034-7562; Peissel,
Bernard/0000-0001-9233-3571; Rahman, Nazneen/0000-0003-4376-0440;
Schoemaker, Minouk/0000-0001-8403-2234; Robson,
Mark/0000-0002-3109-1692; Joseph, Vijai/0000-0002-7933-151X; Hein,
Alexander/0000-0003-2601-3398;
FU European Community [223175, HEALTH-F2-2009-223175]; Cancer Research-UK
[C1287/A10118, C1287/A12014, C8197/A10865]; European Union [BM0606];
Joseph Mitchell Trust; United States National Cancer Institute, National
Institutes of Health (NIH) [RFA-CA-06-503]; National Health and Medical
Research Council of Australia; New South Wales Cancer Council; Victorian
Health Promotion Foundation (Australia); Victorian Breast Cancer
Research Consortium; Dutch Cancer Society [NKI 2001-2423; 2007-3839,
DDHK 2004-3124, DDHK 2009-4318]; Dutch National Genomics Initiative;
Breast Cancer Research Trust; ELAN-Fond of the University Hospital of
Erlangen; Cancer Research UK; Breakthrough Breast Cancer; National
Health Service (NHS); National Cancer Research Network (NCRN); National
Institute for Health Research (NIHR) Comprehensive Biomedical Research
Centre; Guy's & St. Thomas' National Health Service Foundation Trust;
King's College London; Oxford Biomedical Research Centre; Dietmar-Hopp
Foundation; Helmholtz Society; Fondation de France; French National
Institute of Cancer [INCa]; French Agency for Environmental and
Occupational Health [ANSES (ex-AFSSET)]; French League Against Cancer;
National Research Agency (ANR); Chief Physician Johan Boserup and Lise
Boserup Fund; Danish Medical Research Council; Herlev Hospital; Genome
Spain Foundation; Red Tematica de Investigacion Cooperativa en Cancer;
Asociacion Espanola Contra el Cancer; Fondo de Investigacion Sanitario
[PI081120, PI081583]; California Breast Cancer Act; National Institutes
of Health [R01 CA77398, R01CA122340, R01 CA128978]; Lon V Smith
Foundation [LVS39420]; California Breast Cancer Research Fund
[97-10500]; California Department of Public Health [103885]; Baden
Wurttemberg Ministry of Science, Research and Arts; German Cancer Aid
(Deutsche Krebshilfe); Cancer Research UK [C8620/A8372, C8620/A8857,
C490/A11021]; US Military Acquisition (ACQ) Activity, Era of Hope Award
[W81XWH-05-1-0204]; Institute of Cancer Research (UK) a Medical Research
Council (UK); Deutsche Krebshilfe [107054]; Center of Molecular
Medicine, Cologne; Dietmar Hopp Foundation; Dr. Margarete
Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart; University
of Tubingen, Germany; Department of Internal Medicine, Evangelische
Kliniken Bonn GmbH, Johanniter Krankenhaus, Bonn, Germany; Institute of
Pathology, University of Bonn, Bonn, Germany; Molecular Genetics of
Breast Cancer, Deutsches Krebsforschungszentrum (DKFZ), Heidelberg,
Germany; Institute for Prevention and Occupational Medicine of the
German Social Accident Insurance (IPA), Bochum, Germany; Deutsche
Krebshilfe e.V. [70492, 70-2892-BR I]; Hannover Medical School; German
Research Foundation [DFG] [Do761/2-1]; Helsinki University Central
Hospital Research Fund, Academy of Finland [132473]; Finnish Cancer
Society; Sigrid Juselius Foundation; short-term fellowships from the
German Academic Exchange Program; Friends of Hannover Medical School;
German Federal Ministry of Research and Education [RUS08/017]; Swedish
Cancer Society; Stockholm Cancer Society; Kuopio University Hospital of
North Savo; Finnish Cancer Organizations; Academy of Finland; University
of Eastern Finland; National Breast Cancer Foundation; National Health
and Medical Research Council (NHMRC); Queensland Cancer Fund; Cancer
Council of New South Wales, Victoria, Tasmania; Cancer Council of New
South Wales, Victoria, South Australia; Cancer Foundation of Western
Australia; NHMRC [145684, 288704, 454508, 199600]; United States Army
Medical Research and Materiel Command [DAMD17-01-1-0729]; Cancer Council
of Tasmania and Cancer Foundation of Western Australia; Stichting tegen
Kanker [232-2008, 196-2010]; Hamburg Cancer Society; German Cancer
Research Center; Federal Ministry of Education and Research (BMBF)
Germany [01KH0402]; Ministero della Salute; Ministero dell'Universita e
Ricerca [RBLAO3-BETH]; Fondazione Italiana per la Ricerca sul Cancro;
Associazione Italiana per la Ricerca sul Cancro [4017]; Fondazione IRCCS
Istituto Nazionale Tumori [561000]; Specialized Program of Research
Excellence (SPORE) in Breast Cancer [CA116201]; VicHealth; Cancer
Council Victoria; Australian National Health and Medical Research
Council (NHMRC) [209057, 251553, 504711]; Breast Cancer Research
Foundation; Sharon Levine Corzine Fund; Niehaus Cancer Research
Initiative; Andrew Sabin Family Fund; Charles Krasne Research Fund;
Norman and Carol Stone Research Initiative; Norwegian Research council
[155218/V40, 175240/S10, FUGE-NFR 181600/V11]; Swizz Bridge Award;
Finnish Cancer Foundation; University of Oulu; Oulu University Hospital;
National Cancer Institute, National Institutes of Health [RFA]
[CA-06-503]; University of Melbourne [U01 CA69638]; Cancer Care Ontario;
National Cancer Institute, Department of Health and Human Services, USA;
Marit and Hans Rausing Initiative Against Breast Cancer; Agency for
Science, Technology and Research of Singapore (ASTAR); United States
National Institutes of Health (NIH); Susan G. Komen Breast Cancer
Foundation; Yorkshire Cancer Research; Breast Cancer Campaign; Ministry
of Health and Welfare, Republic of Korea [AO30001]; Polish Foundation of
Science; National Cancer Institute Thailand; Institute of Biomedical
Sciences, Academia Sinica, Taiwan; National Institute of Health
[CA58860, CA92044]; Massachusetts center [R01CA47305]; Wisconsin center
[R01 CA47147]; New Hampshire center [R01CA69664];
[PBZ_KBN_122/P05/2004]
FX This work was partly supported by the European Community's Seventh
Framework Programme (COGS; http://cogseu.org/) [grant agreement number
223175, grant number HEALTH-F2-2009-223175]. The Breast Cancer
Association Consortium (BCAC) is funded by Cancer Research-UK
(http://science.cancerresearchuk.org/) [C1287/A10118 and C1287/A12014].
Meetings of the BCAC have been funded by the European Union COST
programme (http://www.srl.cam.ac.uk/consortia/cost/index.html) [BM0606].
D. F. E. is a Principal Research Fellow of Cancer Research-UK. A. C. A.
is a Cancer Research-UK Senior Cancer Research Fellow. A. M. D has been
funded by Cancer Research-UK [C8197/A10865] and The Joseph Mitchell
Trust. The Australian Breast Cancer Family Study (ABCFS) and Northern
California Breast Cancer Family Registry (NC-BCFR) work was supported by
the United States National Cancer Institute, National Institutes of
Health (NIH) [RFA-CA-06-503]; and through cooperative agreements with
members of the Breast Cancer Family Registry (BCFR); and Principal
Investigators, including Cancer Care Ontario [U01 CA69467]; Northern
California Cancer Center [U01 CA69417]; University of Melbourne [U01
CA69638]. Samples from the NC-BCFR were processed and distributed by the
Coriell Institute for Medical Research. The content of this manuscript
does not necessarily reflect the views or policies of the National
Cancer Institute or any of the collaborating centers in the BCFR, nor
does mention of trade names, commercial products, or organizations imply
endorsement by the U. S. Government or the BCFR. The ABCFS was also
supported by the National Health and Medical Research Council of
Australia; the New South Wales Cancer Council; the Victorian Health
Promotion Foundation (Australia); and the Victorian Breast Cancer
Research Consortium. J.L.H. is a National Health and Medical Research
Council (NHMRC) Australia Fellow and a Victorian Breast Cancer Research
Consortium Group Leader. M. C. S. is a NHMRC Senior Research Fellow and
a Victorian Breast Cancer Research Consortium Group Leader. The
Amsterdam Breast Cancer Study (ABCS) study was supported by the Dutch
Cancer Society [NKI 2001-2423; 2007-3839]; and the Dutch National
Genomics Initiative. The Asian Cancer Program (ACP) study was supported
by the Breast Cancer Research Trust. The Bavarian Breast Cancer Cases
and Controls (BBCC) study was partly supported by ELAN-Fond of the
University Hospital of Erlangen. The British Breast Cancer Study (BBCS)
study is supported by Cancer Research UK; and Breakthrough Breast
Cancer; and acknowledges National Health Service (NHS) funding to the
National Institute for Health Research (NIHR) Biomedical Research
Centre; and the National Cancer Research Network (NCRN). Breast Cancer
in Galway Genetic Study (BIGGS) is supported by National Institute for
Health Research (NIHR) Comprehensive Biomedical Research Centre [to E.
S.]; Guy's & St. Thomas' National Health Service Foundation Trust in
partnership with King's College London [to E. S.]; and the Oxford
Biomedical Research Centre [to I. T.]. The Breast Cancer Study of the
University Clinic Heidelberg (BSUCH) study was supported by the
Dietmar-Hopp Foundation; and the Helmholtz Society. The CECILE Breast
Cancer Study (CECILE) study was supported by Fondation de France (2007),
French National Institute of Cancer [INCa grant 2007, 2008, 2009];
French Agency for Environmental and Occupational Health [ANSES
(ex-AFSSET) grant 2008 and 2009]; the French League Against Cancer; and
National Research Agency (ANR).; The Copenhagen General Population Study
(CGPS) was supported by the Chief Physician Johan Boserup and Lise
Boserup Fund; the Danish Medical Research Council; and Herlev Hospital.
The Spanish National Cancer Centre Breast Cancer Study (CNIO-BCS) was
supported by the Genome Spain Foundation; the Red Tematica de
Investigacion Cooperativa en Cancer and grants from the Asociacion
Espanola Contra el Cancer and the Fondo de Investigacion Sanitario
[PI081120 to J.B., PI081583 to R. L. M.]. The California Teachers Study
(CTS) was supported by the California Breast Cancer Act of 1993;
National Institutes of Health [R01 CA77398]; the Lon V Smith Foundation
[LVS39420]; and the California Breast Cancer Research Fund [contract
97-10500]. Collection of cancer incidence data used in this study was
supported by the California Department of Public Health as part of the
statewide cancer reporting program mandated by California Health and
Safety Code Section 103885. The ESTHER Breast Cancer Study (ESTHER)
study was supported by a grant from the Baden Wurttemberg Ministry of
Science, Research and Arts. Additional cases were recruited in the
context of the VERDI study, which was supported by a grant from the
German Cancer Aid (Deutsche Krebshilfe). The ICR Familial Breast Cancer
Study (FBCS) is supported by funds from Cancer Research UK [C8620/A8372;
C8620/A8857]; a US Military Acquisition (ACQ) Activity, Era of Hope
Award [W81XWH-05-1-0204]; the Institute of Cancer Research (UK) a
Medical Research Council (UK) Clinical Research Fellowship [to C. T.].
The FBCS acknowledges National Health Service (NHS) funding to the Royal
Marsden/Institute of Cancer Research, National Institute for Health
Research (NIHR) Specialist Cancer. The German Consortium for Hereditary
Breast & Ovarian Cancer (GC-HBOC) was supported by Deutsche Krebshilfe
[107054]; the Center of Molecular Medicine, Cologne; the Helmholtz
society; and the Dietmar Hopp Foundation [to B. B.]. The Gene
Environment Interaction and Breast Cancer in Germany (GENICA) network
was supported by the Dr. Margarete Fischer-Bosch-Institute of Clinical
Pharmacology, Stuttgart, and the University of Tubingen, Germany [to
C.J. and H. B.]; the Department of Internal Medicine, Evangelische
Kliniken Bonn GmbH, Johanniter Krankenhaus, Bonn, Germany [to Y.D.K. and
C.B.]; the Institute of Pathology, University of Bonn, Bonn, Germany [to
HP. F.]; Molecular Genetics of Breast Cancer, Deutsches
Krebsforschungszentrum (DKFZ), Heidelberg, Germany [to U. H.]; the
Institute for Prevention and Occupational Medicine of the German Social
Accident Insurance (IPA), Bochum, Germany [to T. B., B. P., S. R., A. S.
and V. H.]. The Genetic Epidemiology Study of Breast Cancer by Age 50
(GESBC) was supported by the Deutsche Krebshilfe e.V. [70492]; and
genotyping in part by the state of Baden-Wurttemberg through the Medical
Faculty of the University of Ulm [P.685]. The Hannover Breast Cancer
Study (HABCS) study was supported by an intramural grant from Hannover
Medical School; and by a grant from the German Research Foundation [DFG,
Do761/2-1]. The Helsinki Breast Cancer Study (HEBCS) study has been
financially supported by the Helsinki University Central Hospital
Research Fund, Academy of Finland [132473]; the Finnish Cancer Society;
and the Sigrid Juselius Foundation. The Hannover-Minsk Breast Cancer
Study (HMBCS) was supported by short-term fellowships from the German
Academic Exchange Program [to N.B.]; and the Friends of Hannover Medical
School [to N.B.].; The Hannover-Ufa Breast Cancer Study (HUBCS) was
supported by a grant from the German Federal Ministry of Research and
Education [RUS08/017]. The Karolinska Breast Cancer Study (KARBAC) was
supported by the Swedish Cancer Society and the Stockholm Cancer
Society. The Kuopio Breast Cancer Project (KBCP) was financially
supported by the special Government Funding (EVO) of Kuopio University
Hospital grants, Cancer Fund of North Savo; the Finnish Cancer
Organizations; the Academy of Finland; and by the strategic funding of
the University of Eastern Finland. Kathleen Cuningham Foundation
Consortium for research into Familial Breast Cancer/Australian Ovarian
Cancer Study (KConFab/AOCS) is supported by grants from the National
Breast Cancer Foundation; the National Health and Medical Research
Council (NHMRC); the Queensland Cancer Fund; the Cancer Councils of New
South Wales, Victoria, Tasmania and South Australia; and the Cancer
Foundation of Western Australia. The kConFab Clinical Follow Up Study
was funded by the NHMRC [145684; 288704; 454508]. Financial support for
the AOCS was provided by the United States Army Medical Research and
Materiel Command [DAMD17-01-1-0729]; the Cancer Council of Tasmania and
Cancer Foundation of Western Australia; and the NHMRC [199600]. G. C. T.
and P. W. are supported by the NHMRC. Leuven Multidisciplinary Breast
Centre (LMBC) is supported by the 'Stichting tegen Kanker' [232-2008;
196-2010]. The Mammary Carcinoma Risk Factor Investigation (MARIE) study
was supported by the Deutsche Krebshilfe e.V. [70-2892-BR I]; the
Hamburg Cancer Society; the German Cancer Research Center; and the
genotype work in part by the Federal Ministry of Education and Research
(BMBF) Germany [01KH0402]. Milan Breast Cancer Study Group (MBCSG) was
supported by grants from Ministero della Salute (Extraordinary National
Cancer Program 2006 "Alleanza contro il Cancro", and "Progetto Tumori
Femminili") [to P. R.]; Ministero dell'Universita e Ricerca
(RBLAO3-BETH) [to P. R.]; Fondazione Italiana per la Ricerca sul Cancro
(Special Project "Hereditary tumors"); Associazione Italiana per la
Ricerca sul Cancro (4017) [to P. P.]; and by funds from Italian citizens
who allocated the 5/1000 share of their tax payment in support of the
Fondazione IRCCS Istituto Nazionale Tumori, according to Italian laws
(INT-Institutional strategic projects "561000"). The Mayo Clinic Breast
Cancer Study (MCBCS) was supported by National Institutes of Health
grants [R01CA122340; R01 CA128978]; and a Specialized Program of
Research Excellence (SPORE) in Breast Cancer [CA116201]. Melbourne
Collaborative Cohort Study (MCCS) cohort recruitment was funded by
VicHealth; and Cancer Council Victoria. The MCCS was further supported
by Australian National Health and Medical Research Council (NHMRC)
grants [209057; 251553; 504711]; and by infrastructure provided by
Cancer Council Victoria. The Memorial Sloan-Kettering Cancer Center
(MSKCC) was supported by the Breast Cancer Research Foundation; the
Sharon Levine Corzine Fund; the Niehaus Cancer Research Initiative; the
Andrew Sabin Family Fund; the Charles Krasne Research Fund; and the
Norman and Carol Stone Research Initiative. The Norwegian Breast Cancer
Study (NBCS) was supported by grants from the Norwegian Research council
[155218/V40, 175240/S10 to A. L. B. D.; FUGE-NFR 181600/V11 to V.N.K.];
and a Swizz Bridge Award [to A. L. B. D.].; The Oulu Breast Cancer Study
(OBCS) was supported by research grants from the Finnish Cancer
Foundation; the Sigrid Juselius Foundation; the Academy of Finland; the
University of Oulu; and the Oulu University Hospital. The Ontario
Familial Breast Cancer Registry (OFBCR) work was supported by the
National Cancer Institute, National Institutes of Health [RFA #
CA-06-503]; and through cooperative agreements with members of the
Breast Cancer Family Registry (BCFR); and Principal Investigators,
including Cancer Care Ontario [U01 CA69467]; Northern California Cancer
Center [U01 CA69417]; and University of Melbourne [U01 CA69638]; and by
Cancer Care Ontario. The content of this manuscript does not necessarily
reflect the views or policies of the National Cancer Institute or any of
the collaborating centers in the BCFR, nor does mention of trade names,
commercial products, or organizations imply endorsement by the U. S.
Government or the BCFR. The National Cancer Institute Polish Breast
Cancer Study (PBCS) was supported by Intramural Research Funds of the
National Cancer Institute, Department of Health and Human Services, USA.
The Rotterdam Breast Cancer Study (RBCS) was funded by the Dutch Cancer
Society [DDHK 2004-3124; DDHK 2009-4318]. The Singapore and Sweden
Breast Cancer Study (SASBAC) was funded by the Marit and Hans Rausing
Initiative Against Breast Cancer; the Agency for Science, Technology and
Research of Singapore (ASTAR); the United States National Institutes of
Health (NIH); and the Susan G. Komen Breast Cancer Foundation. The
Sheffield Breast Cancer Study (SBCS) was funded by Yorkshire Cancer
Research; and the Breast Cancer Campaign. The Study of Epidemiology and
Risk factors in Cancer Heredity (SEARCH) study is funded by a programme
grant from Cancer Research UK [C490/A11021] and laboratory
infrastructure by [C8197/A10123]. The Seoul Breast Cancer Study (SEBCS)
was supported by the Korea Health 21 R&D Project [AO30001], Ministry of
Health and Welfare, Republic of Korea. The IHCC-Szczecin Breast Cancer
Study (SZBCS) was supported by Grant PBZ_KBN_122/P05/2004; and the
Polish Foundation of Science [to K.J.]. Katarzyna Jaworska is a fellow
of International PhD program, Postgraduate School of Molecular Medicine,
Warsaw Medical University. The International Agency for Research on
Cancer-Thai Breast Cancer Study (TBCS) was funded by The National Cancer
Institute Thailand. The Taiwanese Breast Cancer Study (TWBCS) is
supported by the Taiwan Biobank project of the Institute of Biomedical
Sciences, Academia Sinica, Taiwan. The University of California, Irvine,
Breast Cancer Study (UCIBCS) component of this research was supported by
the National Institute of Health [CA58860; CA92044]; and the Lon V Smith
Foundation [LVS39420]. The UK Breakthrough Generations Study (UKBGS) is
funded by Breakthrough Breast Cancer. The US Three State Study (US3SS)
study was supported by Massachusetts [R01CA47305 to K. M. E.]; Wisconsin
[R01 CA47147 to P.A.N.]; and New Hampshire [R01CA69664 to L. T.-E.]
centers; and Intramural Research Funds of the National Cancer Institute,
Department of Health and Human Services, USA. The funders had no role in
study design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 13
TC 28
Z9 28
U1 3
U2 24
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 7
PY 2012
VL 7
IS 8
AR e42380
DI 10.1371/journal.pone.0042380
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 987SL
UT WOS:000307437900035
PM 22879957
ER
PT J
AU Hsu, WL
Tse, KP
Liang, SR
Chien, YC
Su, WH
Yu, KJ
Cheng, YJ
Tsang, NM
Hsu, MM
Chang, KP
Chen, IH
Chen, TI
Yang, CS
Goldstein, AM
Chen, CJ
Chang, YS
Hildesheim, A
AF Hsu, Wan-Lun
Tse, Ka-Po
Liang, Sharon
Chien, Yin-Chu
Su, Wen-Hui
Yu, Kelly J.
Cheng, Yu-Juen
Tsang, Ngan-Ming
Hsu, Mow-Ming
Chang, Kai-Ping
Chen, I-How
Chen, Tzu-I
Yang, Czau-Siung
Goldstein, Alisa M.
Chen, Chien-Jen
Chang, Yu-Sun
Hildesheim, Allan
TI Evaluation of Human Leukocyte Antigen-A (HLA-A), Other Non-HLA Markers
on Chromosome 6p21 and Risk of Nasopharyngeal Carcinoma
SO PLOS ONE
LA English
DT Article
ID CLASS-I; SUSCEPTIBILITY; TAIWAN; ASSOCIATION; HAPLOTYPES; ALLELES
AB Background: The association between human leukocyte antigen (HLA) genes (located in the Major Histocompatibility Complex [MHC] region of chromosome 6p21) and NPC has been known for some time. Recently, two genome-wide association studies (GWAS) conducted in Taiwan and China confirmed that the strongest evidence for NPC association was mapped to the MHC region. It is still unclear, however, whether these findings reflect direct associations with Human Leukocyte Antigen (HLA) genes and/or to other genes in this gene-rich region.
Methods: To better understand genetic associations for NPC within the MHC region of chromosome 6, we conducted an evaluation that pooled two previously conducted NPC case-control studies in Taiwan (N = 591 cases and N = 521 controls). PCR-based genotyping was performed for 12 significant SNPs identified within 6p21 in the Taiwan NPC GWAS and for the HLA-A gene (exons 2 and 3).
Findings: After confirming homogeneity between the two studies, pooled odds ratios (OR) and 95% confidence intervals (CI) were estimated by logistic regression. We found that HLA-A (p-trend = 0.0006) and rs29232 (within the GABBR1 gene; p-trend = 0.005) were independent risk factors for NPC after adjustment for age, gender, study and each other. NPC risk was highest among individuals who were homozygous for the HLA-A*0207 risk allele and carriers of the rs29232 risk allele (A).
Conclusion: Our study suggests that most of the SNPs significantly associated with NPC from GWAS reflect previously identified HLA-A associations. An independent effect of rs29232 (GABBR1), however, remained, suggesting that additional genes within this region might be associated with NPC risk.
C1 [Hsu, Wan-Lun; Chen, Tzu-I; Chen, Chien-Jen] Acad Sinica, Genom Res Ctr, Taipei 115, Taiwan.
[Tse, Ka-Po; Chang, Yu-Sun] Chang Gung Univ, Chang Gung Mol Med Res Ctr, Genome Med Core, Tao Yuan, Taiwan.
[Liang, Sharon; Yu, Kelly J.; Goldstein, Alisa M.] NCI, Div Canc Epidemiol & Genet, Rockville, MD USA.
[Liang, Sharon] US FDA, Rockville, MD 20857 USA.
[Chien, Yin-Chu] China Med Univ Hosp, Mol & Genom Epidemiol Res Ctr, Taichung, Taiwan.
[Su, Wen-Hui] Chang Gung Univ, Chang Gung Mol Med Res Ctr, Mol Epidemiol Core, Tao Yuan, Taiwan.
[Su, Wen-Hui] Chang Gung Univ, Grad Inst Biomed Sci, Dept Biomed Sci, Tao Yuan, Taiwan.
[Yu, Kelly J.] NCI, Canc Prevent Div, Rockville, MD USA.
[Cheng, Yu-Juen; Chen, Chien-Jen] Natl Taiwan Univ, Coll Publ Hlth, Grad Inst Epidemiol & Prevent Med, Taipei 10764, Taiwan.
[Tsang, Ngan-Ming] Chang Gung Mem Hosp Lin Kou, Dept Radiat Oncol, Tao Yuan, Taiwan.
[Hsu, Mow-Ming] Natl Taiwan Univ Hosp, Dept Otolaryngol, Taipei, Taiwan.
[Chang, Kai-Ping; Chen, I-How] Chang Gung Mem Hosp Lin Kou, Dept Otolaryngol, Tao Yuan, Taiwan.
[Yang, Czau-Siung] Natl Taiwan Univ, Coll Med, Grad Inst Microbiol, Taipei 10764, Taiwan.
RP Hsu, WL (reprint author), Acad Sinica, Genom Res Ctr, Taipei 115, Taiwan.
EM ysc@mail.cgu.edu.tw
RI Chen, Chien-Jen/C-6976-2008; Hildesheim, Allan/B-9760-2015
OI Hildesheim, Allan/0000-0003-0257-2363
FU National Institutes of Health, USA; Ministry of Education, Taiwan
FX The study was supported by the intramural funds from the National
Institutes of Health, USA and The Top University Project of Ministry of
Education, Taiwan (to Chang Gung University). The funders had no role in
study design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 20
TC 0
Z9 0
U1 0
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 7
PY 2012
VL 7
IS 8
AR e42767
DI 10.1371/journal.pone.0042767
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 987SL
UT WOS:000307437900053
PM 22880099
ER
PT J
AU Mackey, RH
Greenland, P
Goff, DC
Lloyd-Jones, D
Sibley, CT
Mora, S
AF Mackey, Rachel H.
Greenland, Philip
Goff, David C., Jr.
Lloyd-Jones, Donald
Sibley, Christopher T.
Mora, Samia
TI High-Density Lipoprotein Cholesterol and Particle Concentrations,
Carotid Atherosclerosis, and Coronary Events MESA (Multi-Ethnic Study of
Atherosclerosis)
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Article
DE cardiovascular disease; high-density lipoprotein cholesterol;
high-density lipoprotein particles; lipids; lipoproteins
ID TYPE-2 DIABETES-MELLITUS; CARDIOVASCULAR-DISEASE; METABOLIC SYNDROME;
OLDER-ADULTS; RISK; SUBCLASSES; THERAPY; WOMEN; SIZE; LDL
AB Objectives The purpose of this study was to evaluate independent associations of high-density lipoprotein cholesterol (HDL-C) and particle (HDL-P) concentrations with carotid intima-media thickness (cIMT) and incident coronary heart disease (CHD).
Background HDL-C is inversely related to CHD, and also to triglycerides, low-density lipoprotein particles (LDL-P), and related metabolic risk. HDL-P associations with CHD may be partially independent of these factors.
Methods In a multiethnic study of 5,598 men and women ages 45 to 84 years old, without baseline CHD, excluding subjects on lipid-lowering medications, triglycerides >400 mg/dl, or missing values, we evaluated associations of HDL-C and nuclear magnetic resonance spectroscopy-measured HDL-P with cIMT and incident CHD (myocardial infarction, CHD death, and angina, n = 227 events; mean 6.0 years follow-up). All models were adjusted for age, sex, ethnicity, hypertension, and smoking.
Results HDL-C and HDL-P correlated with each other (rho = 0.69) and LDL-P (rho = -0.38, -0.25, respectively, p < 0.05 for all). For (1 SD) higher HDL-C (15 mg/dl) or HDL-P (6.64 mu mol/l), cIMT differences were - 26.1 (95% confidence interval [CI]: -34.7 to -17.4) mu m and -30.1 (95% CI: -38.8 to - 21.4) mu m, and CHD hazard ratios were 0.74 (95% CI: 0.63 to 0.88) and 0.70 (95% CI: 0.59 to 0.82), respectively. Adjusted for each other and LDL-P, HDL-C was no longer associated with cIMT (2.3; 95% CI: - 9.5 to 14.2 mu m) or CHD (0.97; 95% CI: 0.77 to 1.22), but HDL-P remained independently associated with cIMT (-22.2; 95% CI: - 33.8 to -10.6 mu m) and CHD (0.75; 95% CI: 0.61 to 0.93). Interactions by sex, ethnicity, diabetes, and high-sensitivity C-reactive protein were not significant.
Conclusions Adjusting for each other and LDL-P substantially attenuated associations of HDL-C, but not HDL-P, with cIMT and CHD. Potential confounding by related lipids or lipoproteins should be carefully considered when evaluating HDL-related risk. (J Am Coll Cardiol 2012;60:508-16) (C) 2012 by the American College of Cardiology Foundation
C1 [Mackey, Rachel H.] Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA 15261 USA.
[Greenland, Philip; Lloyd-Jones, Donald] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA.
[Goff, David C., Jr.] Wake Forest Univ, Bowman Gray Sch Med, Winston Salem, NC USA.
[Sibley, Christopher T.] NIH, Ctr Clin, Bethesda, MD 20892 USA.
[Mora, Samia] Brigham & Womens Hosp, Boston, MA 02115 USA.
RP Mackey, RH (reprint author), Univ Pittsburgh, Grad Sch Publ Hlth, 130 DeSoto St,A531 Crabtree Hall, Pittsburgh, PA 15261 USA.
EM mackey@edc.pitt.edu
RI Sibley, Christopher/C-9900-2013;
OI Mackey, Rachel/0000-0001-6088-2664
FU National Heart, Lung, and Blood Institute [N01-HC-95159, N01-HC-95169];
LipoScience, Inc.; [K08 HL094375]
FX Dr. Mackey was supported by a research grant from LipoScience, Inc. to
the University of Pittsburgh. The grant was unrestricted because
LipoScience exercised no control over the design, management, analysis,
or interpretation of the data, or in the preparation, review, or
approval of the paper. This research was supported by contracts
N01-HC-95159 through N01-HC-95169 from the National Heart, Lung, and
Blood Institute, an unrestricted grant from LipoScience, Inc., and by
grant K08 HL094375 to Dr. Mora. Dr. Goff is a research consultant for a
clinical trial of a glucose lowering medication marketed by Merck; and a
Data and Safety Monitoring Board member for a clinical trial of a
glucose lowering medication marketed by Takeda. Dr. Mora received a
research grant from AstraZeneca; and honorarium/consultant fees from
Pfizer, Abbott, Quest Diagnostics, and AstraZeneca. All other authors
have reported that they have no relationships relevant to the contents
of this paper to disclose.
NR 39
TC 146
Z9 148
U1 0
U2 16
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD AUG 7
PY 2012
VL 60
IS 6
BP 508
EP 516
DI 10.1016/j.jacc.2012.03.060
PG 9
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 982UR
UT WOS:000307071400005
PM 22796256
ER
PT J
AU Jia, M
Belyavskaya, E
Deuster, P
Sternberg, EM
AF Jia, Min
Belyavskaya, Elena
Deuster, Patricia
Sternberg, Esther M.
TI Development of a Sensitive Microarray Immunoassay for the Quantitative
Analysis of Neuropeptide Y
SO ANALYTICAL CHEMISTRY
LA English
DT Article
ID MAJOR DEPRESSIVE DISORDER; SKIN TISSUE FLUIDS; MASS-SPECTROMETRY;
NERVE-FIBERS; LIQUID-CHROMATOGRAPHY; SWEAT PATCHES; NPY-RECEPTORS;
PLASMA; BRAIN; STRESS
AB A direct competitive immunoassay in an antibody microarray format was developed for the sensitive detection of neuropeptide Y (NPY) and employed in the analysis of NPY in human sweat samples. This is the first demonstration that antibody microarray, as a powerful multiplex analysis tool, can be used for the sensitive determination of NPY and potentially other neuropeptides. 400 pg/mL of dibiotinylated NPY and 0.1 mg/mL spotting capture antibody were found to offer the best performance, yielding a sensitivity of SO pg/mL and a linear dynamic range of 0.1-100 ng/mL for NPY. Evaluation of matrix effects by using artificial sweat revealed that dialysis is necessary for analyzing NPY in human sweat samples with microarray immunoassay. In a preliminary application, 50-210 pg/mL of NPY was detected in sweat samples collected with Macroduct collectors. This study indicates that antibody microarrays can be used for NPY analysis and that human sweat could be a valuable sample source for biomarkers and proteomics studies, especially when noninvasive human sample collection is preferable.
C1 [Jia, Min; Belyavskaya, Elena; Sternberg, Esther M.] NIMH, Sect Neuroendocrine Immunol & Behav, NIH, Bethesda, MD 20892 USA.
[Deuster, Patricia] Uniformed Serv Univ Hlth Sci, Dept Mil & Emergency Med, Bethesda, MD 20814 USA.
RP Sternberg, EM (reprint author), NIMH, Sect Neuroendocrine Immunol & Behav, NIH, Bethesda, MD 20892 USA.
EM sternbee@mail.nih.gov
RI Jia, Min/L-5526-2014; Deuster, Patricia/G-3838-2015
OI Deuster, Patricia/0000-0002-7895-0888
FU Intramural Research Program of the National Institute of Mental Health;
National Center for Complementary and Alternative Medicine, NIH; NIH
Director's Challenge Grant Award (NIH, OD); Center for Neuroscience and
Regenerative Medicine (CNRM) Grant [60855]; Office of Dietary
Supplements [G191FE]; Comprehensive National Neuroscience Program
FX This work was supported by the Intramural Research Program of the
National Institute of Mental Health; the National Center for
Complementary and Alternative Medicine, NIH; NIH Director's Challenge
Grant Award (NIH, OD); and Center for Neuroscience and Regenerative
Medicine (CNRM) Grant [#60855], the Office of Dietary Supplements
(G191FE) and the Comprehensive National Neuroscience Program. We thank
Dr. Terry Phillips for his pioneering work in developing the MC
methodology to establish that cytoldnes and neuropeptides are detectable
in human sweat samples and for his pilot study comparing RIC to the
glass chip microarray method. We would like to thank the staff in the
Human Performance Laboratory at the Uniformed Services University for
their assistance.
NR 41
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Z9 6
U1 0
U2 19
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0003-2700
J9 ANAL CHEM
JI Anal. Chem.
PD AUG 7
PY 2012
VL 84
IS 15
BP 6508
EP 6514
DI 10.1021/ac3014548
PG 7
WC Chemistry, Analytical
SC Chemistry
GA 984AG
UT WOS:000307159200038
PM 22881400
ER
PT J
AU Steeves, JA
Bassett, DR
Fitzhugh, EC
Raynor, HA
Thompson, DL
AF Steeves, Jeremy A.
Bassett, David R.
Fitzhugh, Eugene C.
Raynor, Hollie A.
Thompson, Dixie L.
TI Can sedentary behavior be made more active? A randomized pilot study of
TV commercial stepping versus walking
SO INTERNATIONAL JOURNAL OF BEHAVIORAL NUTRITION AND PHYSICAL ACTIVITY
LA English
DT Article
DE Walking; Physical activity intervention; Obesity; Diet; Weight; Behavior
change; TV commercial stepping
ID PHYSICAL-ACTIVITY; CARDIORESPIRATORY FITNESS; CARDIOVASCULAR-DISEASE;
METABOLIC RISK; PUBLIC-HEALTH; TIME; MORTALITY; OVERWEIGHT; PEDOMETER;
EXERCISE
AB Background: There is a growing problem of physical inactivity in America, and approximately a quarter of the population report being completely sedentary during their leisure time. In the U. S., TV viewing is the most common leisure-time activity. Stepping in place during TV commercials (TV Commercial Stepping) could increase physical activity. The purpose of this study was to examine the feasibility of incorporating physical activity (PA) into a traditionally sedentary activity, by comparing TV Commercial Stepping during 90 min/d of TV programming to traditional exercise (Walking).
Methods: A randomized controlled pilot study of the impact of 6 months of TV Commercial Stepping versus Walking 30 min/day in adults was conducted. 58 sedentary, overweight (body mass index 33.5 +/- 4.8 kg/m(2)) adults (age 52.0 +/- 8.6 y) were randomly assigned to one of two 6-mo behavioral PA programs: 1) TV Commercial Stepping; or 2) Walking 30 min/day. To help facilitate behavior changes participants received 6 monthly phone calls, attended monthly meetings for the first 3 months, and received monthly newsletters for the last 3 months. Using intent-to-treat analysis, changes in daily steps, TV viewing, diet, body weight, waist and hip circumference, and percent fat were compared at baseline, 3, and 6 mo. Data were collected in 2010-2011, and analyzed in 2011.
Results: Of the 58 subjects, 47 (81%) were retained for follow-up at the completion of the 6-mo program. From baseline to 6-mo, both groups significantly increased their daily steps [4611 +/- 1553 steps/d vs. 7605 +/- 2471 steps/d (TV Commercial Stepping); 4909 +/- 1335 steps/d vs. 7865 +/- 1939 steps/d (Walking); P < 0.05] with no significant difference between groups. TV viewing and dietary intake decreased significantly in both groups. Body weight did not change, but both groups had significant decreases in percent body fat (3-mo to 6-mo), and waist and hip circumference (baseline to 6-mo) over time.
Conclusions: Participants in both the TV Commercial Stepping and Walking groups had favorable changes in daily steps, TV viewing, diet, and anthropometrics. PA can be performed while viewing TV commercials and this may be a feasible alternative to traditional approaches for increasing daily steps in overweight and obese adults.
C1 [Steeves, Jeremy A.] NCI, Canc Prevent Fellowship Program, Bethesda, MD 20892 USA.
[Bassett, David R.; Fitzhugh, Eugene C.; Thompson, Dixie L.] Univ Tennessee, Dept Kinesiol Recreat & Sport Studies, Knoxville, TN USA.
[Raynor, Hollie A.] Univ Tennessee, Dept Nutr, Knoxville, TN 37996 USA.
RP Steeves, JA (reprint author), NCI, Canc Prevent Fellowship Program, 6120 Execut Blvd, Bethesda, MD 20892 USA.
EM jeremy.steeves@nih.gov
OI Thompson, Dixie/0000-0001-9944-0206
FU American College of Sports Medicine Foundation
FX We would like to thank Betsy Anderson, Jessica Chandler, Andrew Howard,
Kirby Talman, Ashley Miller, Pam Andrews, and Vaishali Keshani for their
excellent help with supporting the implementation of the trial, data
collection, and data entry. We would like to thank Cary Springer for her
excellent help with data analyses. This research was supported and
funded by the Plus One Active Research Grant on Wellness from the
American College of Sports Medicine Foundation.
NR 38
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Z9 13
U1 1
U2 14
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1479-5868
J9 INT J BEHAV NUTR PHY
JI Int. J. Behav. Nutr. Phys. Act.
PD AUG 6
PY 2012
VL 9
AR 95
DI 10.1186/1479-5868-9-95
PG 9
WC Nutrition & Dietetics; Physiology
SC Nutrition & Dietetics; Physiology
GA 029TF
UT WOS:000310518100001
PM 22866941
ER
PT J
AU Crea, F
Sun, L
Mai, A
Chiang, YT
Farrar, WL
Danesi, R
Helgason, CD
AF Crea, Francesco
Sun, Lei
Mai, Antonello
Chiang, Yan Ting
Farrar, William L.
Danesi, Romano
Helgason, Cheryl D.
TI The emerging role of histone lysine demethylases in prostate cancer
SO MOLECULAR CANCER
LA English
DT Review
DE Prostate cancer; Epigenetics; Tumor-initiating cells; Histone
demethylase; Androgen receptor
ID ANDROGEN RECEPTOR EXPRESSION; STEM-CELLS; DEACETYLASE INHIBITORS;
STEM/PROGENITOR CELLS; MONOAMINE-OXIDASE; TUMOR PROGRESSION;
GENE-EXPRESSION; BONE METASTASIS; 2 EZH2; LSD1
AB Early prostate cancer (PCa) is generally treatable and associated with good prognosis. After a variable time, PCa evolves into a highly metastatic and treatment-refractory disease: castration-resistant PCa (CRPC). Currently, few prognostic factors are available to predict the emergence of CRPC, and no curative option is available. Epigenetic gene regulation has been shown to trigger PCa metastasis and androgen-independence. Most epigenetic studies have focused on DNA and histone methyltransferases. While DNA methylation leads to gene silencing, histone methylation can trigger gene activation or inactivation, depending on the target amino acid residues and the extent of methylation (me1, me2, or me3). Interestingly, some histone modifiers are essential for PCa tumor-initiating cell (TIC) self-renewal. TICs are considered the seeds responsible for metastatic spreading and androgen-independence. Histone Lysine Demethylases (KDMs) are a novel class of epigenetic enzymes which can remove both repressive and activating histone marks. KDMs are currently grouped into 7 major classes, each one targeting a specific methylation site. Since their discovery, KDM expression has been found to be deregulated in several neoplasms. In PCa, KDMs may act as either tumor suppressors or oncogenes, depending on their gene regulatory function. For example, KDM1A and KDM4C are essential for PCa androgen-dependent proliferation, while PHF8 is involved in PCa migration and invasion. Interestingly, the possibility of pharmacologically targeting KDMs has been demonstrated. In the present paper, we summarize the emerging role of KDMs in regulating the metastatic potential and androgen-dependence of PCa. In addition, we speculate on the possible interaction between KDMs and other epigenetic effectors relevant for PCa TICs. Finally, we explore the role of KDMs as novel prognostic factors and therapeutic targets. We believe that studies on histone demethylation may add a novel perspective in our efforts to prevent and cure advanced PCa.
C1 [Crea, Francesco; Chiang, Yan Ting; Helgason, Cheryl D.] British Columbia Canc Res Ctr, Vancouver, BC V5Z 1L3, Canada.
[Helgason, Cheryl D.] Univ British Columbia, Fac Med, Dept Surg, Vancouver, BC V5Z 4E3, Canada.
[Danesi, Romano] Univ Pisa, Dept Internal Med, Div Pharmacol, I-56100 Pisa, Italy.
[Sun, Lei; Farrar, William L.] Frederick Natl Lab Canc Res, Canc Stem Cell Sect, Lab Canc Prevent, Frederick, MD 21702 USA.
[Mai, Antonello] Univ Roma La Sapienza, Dept Drug Chem & Technol, I-00185 Rome, Italy.
RP Crea, F (reprint author), British Columbia Canc Res Ctr, 675 W 10th Ave, Vancouver, BC V5Z 1L3, Canada.
EM fcrea@bccrc.ca; chelgaso@bccrc.ca
RI Crea, Francesco /I-8383-2015; Sun, Lei/J-9943-2015;
OI Crea, Francesco/0000-0002-4903-2973; Mai, Antonello/0000-0001-9176-2382
FU PRIN [2009PX2T2E]; FP7 Project [BLUEPRINT/282510]; Prostate Cancer
Canada [2010-556]
FX This work was partially supported by PRIN 2009PX2T2E and FP7 Project
BLUEPRINT/282510 (A.M.), as well as Prostate Cancer Canada (grant number
2010-556; CDH).
NR 71
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Z9 29
U1 1
U2 24
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1476-4598
J9 MOL CANCER
JI Mol. Cancer
PD AUG 6
PY 2012
VL 11
AR 52
DI 10.1186/1476-4598-11-52
PG 10
WC Biochemistry & Molecular Biology; Oncology
SC Biochemistry & Molecular Biology; Oncology
GA 005KV
UT WOS:000308750200001
PM 22867098
ER
PT J
AU Daniel, JA
Pellegrini, M
Lee, BS
Guo, Z
Filsuf, D
Belkina, NV
You, ZS
Paull, TT
Sleckman, BP
Feigenbaum, L
Nussenzweig, A
AF Daniel, Jeremy A.
Pellegrini, Manuela
Lee, Baeck-Seung
Guo, Zhi
Filsuf, Darius
Belkina, Natalya V.
You, Zhongsheng
Paull, Tanya T.
Sleckman, Barry P.
Feigenbaum, Lionel
Nussenzweig, Andre
TI Loss of ATM kinase activity leads to embryonic lethality in mice
SO JOURNAL OF CELL BIOLOGY
LA English
DT Article
ID DOUBLE-STRAND BREAKS; CLASS SWITCH RECOMBINATION; DNA-DAMAGE RESPONSE;
ACTIVATION IN-VIVO; ATAXIA-TELANGIECTASIA; HOMOLOGOUS RECOMBINATION;
V(D)J RECOMBINATION; IONIZING-RADIATION; DEFICIENT MICE; MUTANT MICE
AB Ataxia telangiectasia (A-T) mutated (ATM) is a key deoxyribonucleic acid (DNA) damage signaling kinase that regulates DNA repair, cell cycle checkpoints, and apoptosis. The majority of patients with A-T, a cancer-prone neurodegenerative disease, present with null mutations in Atm. To determine whether the functions of ATM are mediated solely by its kinase activity, we generated two mouse models containing single, catalytically inactivating point mutations in Atm. In this paper, we show that, in contrast to Atm-null mice, both D2899A and Q2740P mutations cause early embryonic lethality in mice, without displaying dominant-negative interfering activity. Using conditional deletion, we find that the D2899A mutation in adult mice behaves largely similar to Atm-null cells but shows greater deficiency in homologous recombination (HR) as measured by hypersensitivity to poly (adenosine diphosphate-ribose) polymerase inhibition and increased genomic instability. These results may explain why missense mutations with no detectable kinase activity are rarely found in patients with classical A-T. We propose that ATM kinase-inactive missense mutations, unless otherwise compensated for, interfere with HR during embryogenesis.
C1 [Daniel, Jeremy A.; Pellegrini, Manuela; Filsuf, Darius; Nussenzweig, Andre] NCI, Lab Genome Integr, NIH, Bethesda, MD 20814 USA.
[Belkina, Natalya V.] NCI, Expt Immunol Branch, NIH, Bethesda, MD 20814 USA.
[Feigenbaum, Lionel] NCI, Sci Applicat Int Corp Frederick, Frederick Canc Res & Dev Ctr, NIH, Bethesda, MD 20814 USA.
[Daniel, Jeremy A.] Univ Copenhagen, Fac Hlth Sci, Novo Nordisk Fdn Ctr Prot Res, DK-2200 Copenhagen N, Denmark.
[Pellegrini, Manuela] Univ Roma La Sapienza, Dept Expt Med, I-00184 Rome, Italy.
[Lee, Baeck-Seung; Sleckman, Barry P.] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA.
[You, Zhongsheng] Washington Univ, Sch Med, Dept Cell Biol & Physiol, St Louis, MO 63110 USA.
[Guo, Zhi; Paull, Tanya T.] Univ Texas Austin, Howard Hughes Med Inst, Dept Mol Genet & Microbiol, Austin, TX 78705 USA.
[Guo, Zhi; Paull, Tanya T.] Univ Texas Austin, Inst Cellular & Mol Biol, Austin, TX 78705 USA.
[Guo, Zhi] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
RP Daniel, JA (reprint author), NCI, Lab Genome Integr, NIH, Bethesda, MD 20814 USA.
EM jeremy.daniel@cpr.ku.dk; andre_nussenzweig@nih.gov
RI Guo, Zhi/A-4589-2013; Daniel, Jeremy/S-4729-2016
OI Daniel, Jeremy/0000-0002-1981-5571
FU Italian Association for Cancer Research; Intramural Research Program of
the National Institutes of Health; National Cancer Institute; Center for
Cancer Research; Novo Nordisk Foundation; National Institutes of Health
Pathway to Independence Award [K99/R00]
FX This work was supported by funding from the Italian Association for
Cancer Research to M. Pellegrini, from the Intramural Research Program
of the National Institutes of Health, National Cancer Institute, and
Center for Cancer Research to A. Nussenzweig. The Center for Protein
Research is partly supported by a generous donation from the Novo
Nordisk Foundation. J.A. Daniel is the recipient of a National
Institutes of Health Pathway to Independence K99/R00 Award.
NR 78
TC 40
Z9 41
U1 0
U2 14
PU ROCKEFELLER UNIV PRESS
PI NEW YORK
PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA
SN 0021-9525
J9 J CELL BIOL
JI J. Cell Biol.
PD AUG 6
PY 2012
VL 198
IS 3
BP 295
EP 304
DI 10.1083/jcb.201204035
PG 10
WC Cell Biology
SC Cell Biology
GA 987JE
UT WOS:000307412200007
PM 22869595
ER
PT J
AU Brim, H
Lee, E
Abu-Asab, MS
Chaouchi, M
Razjouyan, H
Namin, H
Goel, A
Schaffer, AA
Ashktorab, H
AF Brim, Hassan
Lee, Edward
Abu-Asab, Mones S.
Chaouchi, Mohamed
Razjouyan, Hadi
Namin, Hassanzadeh
Goel, Ajay
Schaeffer, Alejandro A.
Ashktorab, Hassan
TI Genomic Aberrations in an African American Colorectal Cancer Cohort
Reveals a MSI-Specific Profile and Chromosome X Amplification in Male
Patients
SO PLOS ONE
LA English
DT Article
ID TUMOR-SUPPRESSOR GENES; SPORADIC COLON-CANCER; MICROSATELLITE
INSTABILITY; HUMAN BREAST; EXPRESSION; CARCINOMAS; DISTINCT;
HYPERMETHYLATION; HYBRIDIZATION; ABNORMALITIES
AB Objective: DNA aberrations that cause colorectal cancer (CRC) occur in multiple steps that involve microsatellite instability (MSI) and chromosomal instability (CIN). Herein, we studied CRCs from AA patients for their CIN and MSI status.
Experimental Design: Array CGH was performed on 30 AA colon tumors. The MSI status was established. The CGH data from AA were compared to published lists of 41 TSG and oncogenes in Caucasians and 68 cancer genes, proposed via systematic sequencing for somatic mutations in colon and breast tumors. The patient-by-patient CGH profiles were organized into a maximum parsimony cladogram to give insights into the tumors' aberrations lineage.
Results: The CGH analysis revealed that CIN was independent of age, gender, stage or location. However, both the number and nature of aberrations seem to depend on the MSI status. MSI-H tumors clustered together in the cladogram. The chromosomes with the highest rates of CGH aberrations were 3, 5, 7, 8, 20 and X. Chromosome X was primarily amplified in male patients. A comparison with Caucasians revealed an overall similar aberration profile with few exceptions for the following genes; THRB, RAF1, LPL, DCC, XIST, PCNT, STS and genes on the 20q12-q13 cytoband. Among the 68 CAN genes, all showed some level of alteration in our cohort.
Conclusion: Chromosome X amplification in male patients with CRC merits follow-up. The observed CIN may play a distinctive role in CRC in AAs. The clustering of MSI-H tumors in global CGH data analysis suggests that chromosomal aberrations are not random.
C1 [Brim, Hassan; Lee, Edward; Razjouyan, Hadi; Namin, Hassanzadeh; Ashktorab, Hassan] Howard Univ, Dept Med, Washington, DC 20059 USA.
[Brim, Hassan; Lee, Edward; Razjouyan, Hadi; Namin, Hassanzadeh; Ashktorab, Hassan] Howard Univ, Coll Med, Ctr Canc, Dept Pathol, Washington, DC USA.
[Abu-Asab, Mones S.] NCI, NIH, DHHS, Bethesda, MD 20892 USA.
[Chaouchi, Mohamed] Georgetown Univ, Sch Med, Dept Physiol & Biophys, Washington, DC 20007 USA.
[Goel, Ajay] Baylor Univ, Med Ctr, Baylor Res Inst, Dallas, TX USA.
[Goel, Ajay] Baylor Univ, Med Ctr, Sammons Canc Ctr, Dallas, TX USA.
[Schaeffer, Alejandro A.] NIH, Natl Ctr Biotechnol Informat, DHHS, Bethesda, MD 20892 USA.
RP Brim, H (reprint author), Howard Univ, Dept Med, Washington, DC 20059 USA.
EM hbrim@howard.edu; hashktorab@howard.edu
OI Abu-Asab, Mones/0000-0002-4047-1232
FU National Cancer Institute (NCI), National Institutes of Health; National
Institutes of Health, National Cancer Institute and National Library of
Medicine; Research Centers in Minority Institutions (RCMI); [CA102681]
FX This work was supported by Grant #CA102681, funded by the National
Cancer Institute (NCI), National Institutes of Health, by the Intramural
Research Program of the National Institutes of Health, National Cancer
Institute and National Library of Medicine, and by Research Centers in
Minority Institutions (RCMI). The funders had no role in study design,
data collection and analysis, decision to publish, or preparation of the
manuscript.
NR 55
TC 13
Z9 13
U1 0
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 6
PY 2012
VL 7
IS 8
AR e40392
DI 10.1371/journal.pone.0040392
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 992WD
UT WOS:000307810000004
PM 22879877
ER
PT J
AU Lopman, BA
Pitzer, VE
Sarkar, R
Gladstone, B
Patel, M
Glasser, J
Gambhir, M
Atchison, C
Grenfell, BT
Edmunds, WJ
Kang, G
Parashar, UD
AF Lopman, Benjamin A.
Pitzer, Virginia E.
Sarkar, Rajiv
Gladstone, Beryl
Patel, Manish
Glasser, John
Gambhir, Manoj
Atchison, Christina
Grenfell, Bryan T.
Edmunds, W. John
Kang, Gagandeep
Parashar, Umesh D.
TI Understanding Reduced Rotavirus Vaccine Efficacy in Low Socio-Economic
Settings
SO PLOS ONE
LA English
DT Article
ID FINNISH CHILDREN; DOUBLE-BLIND; CVD 103-HGR; SAFETY; GASTROENTERITIS;
INFANTS; IMMUNOGENICITY; DIARRHEA; AUSTRALIA; MORTALITY
AB Introduction: Rotavirus vaccine efficacy ranges from >90% in high socio-economic settings (SES) to 50% in low SES. With the imminent introduction of rotavirus vaccine in low SES countries, understanding reasons for reduced efficacy in these settings could identify strategies to improve vaccine performance.
Methods: We developed a mathematical model to predict rotavirus vaccine efficacy in high, middle and low SES based on data specific for each setting on incidence, protection conferred by natural infection and immune response to vaccination. We then examined factors affecting efficacy.
Results: Vaccination was predicted to prevent 93%, 86% and 51% of severe rotavirus gastroenteritis in high, middle and low SES, respectively. Also predicted was that vaccines are most effective against severe disease and efficacy declines with age in low but not high SES. Reduced immunogenicity of vaccination and reduced protection conferred by natural infection are the main factors that compromise efficacy in low SES.
Discussion: The continued risk of severe disease in non-primary natural infections in low SES is a key factor underpinning reduced efficacy of rotavirus vaccines. Predicted efficacy was remarkably consistent with observed clinical trial results from different SES, validating the model. The phenomenon of reduced vaccine efficacy can be predicted by intrinsic immunological and epidemiological factors of low SES populations. Modifying aspects of the vaccine (e. g. improving immunogenicity in low SES) and vaccination program (e. g. additional doses) may bring improvements.
C1 [Lopman, Benjamin A.; Patel, Manish; Glasser, John; Gambhir, Manoj; Parashar, Umesh D.] Ctr Dis Control & Prevent, Natl Ctr Immunizat & Resp Dis, Atlanta, GA 30333 USA.
[Pitzer, Virginia E.; Grenfell, Bryan T.] Princeton Univ, Dept Ecol & Evolutionary Biol, Princeton, NJ 08544 USA.
[Pitzer, Virginia E.; Grenfell, Bryan T.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Sarkar, Rajiv; Gladstone, Beryl] Christian Med Coll & Hosp, Dept Gastrointestinal Sci, Vellore, Tamil Nadu, India.
[Gambhir, Manoj; Kang, Gagandeep] Univ London Imperial Coll Sci Technol & Med, MRC Ctr Outbreaks Anal & Modelling, London, England.
[Atchison, Christina; Edmunds, W. John] London Sch Hyg & Trop Med, Dept Infect Dis Epidemiol, London WC1, England.
RP Lopman, BA (reprint author), Ctr Dis Control & Prevent, Natl Ctr Immunizat & Resp Dis, Atlanta, GA 30333 USA.
EM blopman@cdc.gov
OI Atchison, Christina/0000-0001-8304-7389; Pitzer,
Virginia/0000-0003-1015-2289
FU National Institutes of Health [R01 GM083983-01]; Bill and Melinda Gates
Foundation; RAPIDD program of the Science & Technology Directorate,
Department of Homeland Security; Fogarty International Center, National
Institutes of Health; Global Alliance for Vaccines and Immunisation
(GAVI)
FX This work was supported by the National Institutes of Health (R01
GM083983-01), the Bill and Melinda Gates Foundation, the RAPIDD program
of the Science & Technology Directorate, Department of Homeland
Security, the Fogarty International Center, National Institutes of
Health (V. E. P and B. G.). Additional Support for this project was
provided by Program for Appropriate Technology in Health (PATH) through
funding from the Global Alliance for Vaccines and Immunisation (GAVI).
The views expressed by the authors do not necessarily reflect the views
of GAVI and/or PATH. The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 38
TC 28
Z9 28
U1 3
U2 14
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 6
PY 2012
VL 7
IS 8
AR e41720
DI 10.1371/journal.pone.0041720
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 992WD
UT WOS:000307810000009
PM 22879893
ER
PT J
AU Pearce, MS
Salotti, JA
Little, MP
McHugh, K
Lee, C
Kim, KP
Howe, NL
Ronckers, CM
Rajaraman, P
Craft, AW
Parker, L
de Gonzalez, AB
AF Pearce, Mark S.
Salotti, Jane A.
Little, Mark P.
McHugh, Kieran
Lee, Choonsik
Kim, Kwang Pyo
Howe, Nicola L.
Ronckers, Cecile M.
Rajaraman, Preetha
Craft, Alan W.
Parker, Louise
de Gonzalez, Amy Berrington
TI Radiation exposure from CT scans in childhood and subsequent risk of
leukaemia and brain tumours: a retrospective cohort study
SO LANCET
LA English
DT Article
ID COMPUTED-TOMOGRAPHY; IONIZING-RADIATION; PEDIATRIC-PATIENTS; CANCER
INCIDENCE; CHILDREN; BODY
AB Background Although CT scans are very useful clinically, potential cancer risks exist from associated ionising radiation, in particular for children who are more radiosensitive than adults. We aimed to assess the excess risk of leukaemia and brain tumours after CT scans in a cohort of children and young adults.
Methods In our retrospective cohort study, we included patients without previous cancer diagnoses who were first examined with CT in National Health Service (NHS) centres in England, Wales, or Scotland (Great Britain) between 1985 and 2002, when they were younger than 22 years of age. We obtained data for cancer incidence, mortality, and loss to follow-up from the NHS Central Registry from Jan 1, 1985, to Dec 31, 2008. We estimated absorbed brain and red bone marrow doses per CT scan in mGy and assessed excess incidence of leukaemia and brain tumours cancer with Poisson relative risk models. To avoid inclusion of CT scans related to cancer diagnosis, follow-up for leukaemia began 2 years after the first CT and for brain tumours 5 years after the first CT.
Findings During follow-up, 74 of 178 604 patients were diagnosed with leukaemia and 135 of 176 587 patients were diagnosed with brain tumours. We noted a positive association between radiation dose from CT scans and leukaemia (excess relative risk [ERR] per mGy 0.036, 95% CI 0.005-0.120; p=0.0097) and brain tumours (0.023, 0.010-0.049; p<0.0001). Compared with patients who received a dose of less than 5 mGy, the relative risk of leukaemia for patients who received a cumulative dose of at least 30 mGy (mean dose 51.13 mGy) was 3.18 (95% CI 1.46-6.94) and the relative risk of brain cancer for patients who received a cumulative dose of 50-74 mGy (mean dose 60.42 mGy) was 2.82 (1.33-6.03).
Interpretation Use of CT scans in children to deliver cumulative doses of about 50 mGy might almost triple the risk of leukaemia and doses of about 60 mGy might triple the risk of brain cancer. Because these cancers are relatively rare, the cumulative absolute risks are small: in the 10 years after the first scan for patients younger than 10 years, one excess case of leukaemia and one excess case of brain tumour per 10 000 head CT scans is estimated to occur. Nevertheless, although clinical benefits should outweigh the small absolute risks, radiation doses from CT scans ought to be kept as low as possible and alternative procedures, which do not involve ionising radiation, should be considered if appropriate.
C1 [Pearce, Mark S.; Salotti, Jane A.; Howe, Nicola L.] Newcastle Univ, Royal Victoria Infirm, Sir James Spence Inst, Inst Hlth & Soc, Newcastle Upon Tyne NE1 4LP, Tyne & Wear, England.
[Craft, Alan W.] Newcastle Univ, Royal Victoria Infirm, Sir James Spence Inst, No Inst Canc Res, Newcastle Upon Tyne NE1 4LP, Tyne & Wear, England.
[Little, Mark P.; Lee, Choonsik; Ronckers, Cecile M.; Rajaraman, Preetha; de Gonzalez, Amy Berrington] NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[McHugh, Kieran] Children NHS Trust, Great Ormond St Hosp, London, England.
[Kim, Kwang Pyo] Kyung Hee Univ, Dept Nucl Engn, Gyeongi Do, South Korea.
[Ronckers, Cecile M.] Dutch Childhood Oncol Grp Longterm Effects Childh, The Hague, Netherlands.
[Parker, Louise] Dalhousie Univ, Populat Canc Res Program, Dept Med, Halifax, NS, Canada.
[Parker, Louise] Dalhousie Univ, Populat Canc Res Program, Dept Paediat, Halifax, NS, Canada.
RP Pearce, MS (reprint author), Newcastle Univ, Royal Victoria Infirm, Sir James Spence Inst, Inst Hlth & Soc, Newcastle Upon Tyne NE1 4LP, Tyne & Wear, England.
EM mark.pearce@ncl.ac.uk
RI Lee, Choonsik/C-9023-2015;
OI Lee, Choonsik/0000-0003-4289-9870; Little, Mark/0000-0003-0980-7567
FU US National Cancer Institute [NO2-CP-75501]; UK Department of Health
[RRX119]; North of England Children's Cancer Research Fund
FX This study was supported by contract NO2-CP-75501 from the US National
Cancer Institute and by the Radiation Research Programme of the UK
Department of Health (RRX119). We thank the North of England Children's
Cancer Research Fund for their continued support of paediatric cancer
epidemiology studies at Newcastle University (Newcastle upon Tyne, UK);
the staff in radiology departments across Great Britain who contributed
data; Richard Hardy, Katharine Kirton, and Wenhua Metcalf from Newcastle
University; Jeremy Miller (Information Management Services, Rockville,
MD, USA); and Martha Linet and Lindsay Morton from the National Cancer
Institute (Bethesda, MD, USA) for their assistance. Elaine Ron, who was
one of the original investigators for this study, died of cancer on Nov
20, 2010. We greatly appreciate her contributions, support, and devotion
to this study and to the field of radiation epidemiology.
NR 31
TC 959
Z9 992
U1 10
U2 111
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0140-6736
J9 LANCET
JI Lancet
PD AUG 4
PY 2012
VL 380
IS 9840
BP 499
EP 505
DI 10.1016/S0140-6736(12)60815-0
PG 7
WC Medicine, General & Internal
SC General & Internal Medicine
GA 983GY
UT WOS:000307109000031
PM 22681860
ER
PT J
AU Varudkar, NM
Xia, JX
Abukenda, I
Pfeifer, K
Ebert, S
AF Varudkar, Namita M.
Xia, Jixiang
Abukenda, Ibrahim
Pfeifer, Karl
Ebert, Steven
TI Pnmt plus "Primer" Cells Give Rise to Cardiac Myocytes and Neurons in
the Mammalian Heart: Development of New Experimental Tools for Cardiac
Regenerative Medicine Applications
SO CIRCULATION RESEARCH
LA English
DT Meeting Abstract
CT Basic Cardiovascular Sciences Scientific Session
CY JUL 23-26, 2012
CL New Orleans, LA
DE Stem cells; Cardiac regeneration
C1 [Varudkar, Namita M.; Xia, Jixiang; Abukenda, Ibrahim; Ebert, Steven] Univ Cent Florida, Orlando, FL 32816 USA.
[Pfeifer, Karl] NICHD, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7330
J9 CIRC RES
JI Circ.Res.
PD AUG 3
PY 2012
VL 111
IS 4
SU S
MA 78
PG 1
WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular
Disease
SC Cardiovascular System & Cardiology; Hematology
GA 056QO
UT WOS:000312506400075
ER
PT J
AU Zhang, QJ
Rai, G
Jadhav, A
Simeonov, A
Maloney, D
Liu, ZP
AF Zhang, Qing-Jun
Rai, Ganesha
Jadhav, Ajit
Simeonov, Anton
Maloney, David
Liu, Zhi-Ping
TI Targeting Cardiac Hypertrophy with Small Molecule Inhibitors of JMJD2A
SO CIRCULATION RESEARCH
LA English
DT Meeting Abstract
CT Basic Cardiovascular Sciences Scientific Session
CY JUL 23-26, 2012
CL New Orleans, LA
DE Cardiac hypertrophy; Cardioprotection
C1 [Zhang, Qing-Jun; Liu, Zhi-Ping] UT SW Med Cntr Dallas, Dallas, TX USA.
[Rai, Ganesha; Jadhav, Ajit; Simeonov, Anton; Maloney, David] NIH, Chem Genom Cntr, Natl Cntr Adv Translat Sci, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7330
J9 CIRC RES
JI Circ.Res.
PD AUG 3
PY 2012
VL 111
IS 4
SU S
MA 119
PG 1
WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular
Disease
SC Cardiovascular System & Cardiology; Hematology
GA 056QO
UT WOS:000312506400112
ER
PT J
AU Raimondi, S
Gandini, S
Fargnoli, MC
Bagnardi, V
Maisonneuve, P
Specchia, C
Kumar, R
Nagore, E
Han, JL
Hansson, J
Kanetsky, PA
Ghiorzo, P
Gruis, NA
Dwyer, T
Blizzard, L
Fernandez-De-Misa, R
Branicki, W
Debniak, T
Morling, N
Landi, MT
Palmieri, G
Ribas, G
Stratigos, A
Cornelius, L
Motokawa, T
Anno, S
Helsing, P
Wong, TH
Autier, P
Garcia-Borron, JC
Little, J
Newton-Bishop, J
Sera, F
Liu, F
Kayser, M
Nijsten, T
AF Raimondi, Sara
Gandini, Sara
Fargnoli, Maria Concetta
Bagnardi, Vincenzo
Maisonneuve, Patrick
Specchia, Claudia
Kumar, Rajiv
Nagore, Eduardo
Han, Jiali
Hansson, Johan
Kanetsky, Peter A.
Ghiorzo, Paola
Gruis, Nelleke A.
Dwyer, Terry
Blizzard, Leigh
Fernandez-de-Misa, Ricardo
Branicki, Wojciech
Debniak, Tadeusz
Morling, Niels
Landi, Maria Teresa
Palmieri, Giuseppe
Ribas, Gloria
Stratigos, Alexander
Cornelius, Lynn
Motokawa, Tomonori
Anno, Sumiko
Helsing, Per
Wong, Terence H.
Autier, Philippe
Garcia-Borron, Jose C.
Little, Julian
Newton-Bishop, Julia
Sera, Francesco
Liu, Fan
Kayser, Manfred
Nijsten, Tamar
CA Grp, GS
M SKIP Study Grp
TI Melanocortin-1 receptor, skin cancer and phenotypic characteristics
(M-SKIP) project: study design and methods for pooling results of
genetic epidemiological studies
SO BMC MEDICAL RESEARCH METHODOLOGY
LA English
DT Article
DE Genetic epidemiology; Melanoma; Meta-analysis; Pooled-analysis; Skin
cancer; Study design
ID MELANOCYTE-STIMULATING HORMONE; BASAL-CELL CARCINOMA; CUTANEOUS
MALIGNANT-MELANOMA; RED HAIR COLOR; MC1R GENE; LOGIC REGRESSION;
POOLED-ANALYSIS; RISK-FACTORS; MEDITERRANEAN POPULATION; PIGMENTATION
PHENOTYPE
AB Background: For complex diseases like cancer, pooled-analysis of individual data represents a powerful tool to investigate the joint contribution of genetic, phenotypic and environmental factors to the development of a disease. Pooled-analysis of epidemiological studies has many advantages over meta-analysis, and preliminary results may be obtained faster and with lower costs than with prospective consortia.
Design and methods: Based on our experience with the study design of the Melanocortin-1 receptor (MC1R) gene, SKin cancer and Phenotypic characteristics (M-SKIP) project, we describe the most important steps in planning and conducting a pooled-analysis of genetic epidemiological studies. We then present the statistical analysis plan that we are going to apply, giving particular attention to methods of analysis recently proposed to account for between-study heterogeneity and to explore the joint contribution of genetic, phenotypic and environmental factors in the development of a disease. Within the M-SKIP project, data on 10,959 skin cancer cases and 14,785 controls from 31 international investigators were checked for quality and recoded for standardization. We first proposed to fit the aggregated data with random-effects logistic regression models. However, for the M-SKIP project, a two-stage analysis will be preferred to overcome the problem regarding the availability of different study covariates. The joint contribution of MC1R variants and phenotypic characteristics to skin cancer development will be studied via logic regression modeling.
Discussion: Methodological guidelines to correctly design and conduct pooled-analyses are needed to facilitate application of such methods, thus providing a better summary of the actual findings on specific fields.
C1 [Raimondi, Sara; Gandini, Sara; Bagnardi, Vincenzo; Maisonneuve, Patrick] European Inst Oncol, Div Epidemiol & Biostat, I-20141 Milan, Italy.
[Raimondi, Sara] Univ Milan, Dept Occupat Hlth, Milan, Italy.
[Fargnoli, Maria Concetta] Univ LAquila, Dept Dermatol, Laquila, Italy.
[Bagnardi, Vincenzo] Univ Milano Bicocca, Dept Stat, Milan, Italy.
[Specchia, Claudia] Univ Brescia, Dept Biomed Sci & Technol, Brescia, Italy.
[Kumar, Rajiv] German Canc Res Ctr, Div Mol Genet Epidemiol, D-6900 Heidelberg, Germany.
[Nagore, Eduardo] Inst Valenciano Oncol, Dept Dermatol, Valencia, Spain.
[Han, Jiali] Brigham & Womens Hosp, Dept Dermatol, Boston, MA 02115 USA.
[Han, Jiali] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA.
[Han, Jiali] Harvard Univ, Sch Med, Dept Epidemiol, Boston, MA USA.
[Hansson, Johan] Karolinska Inst, Ctr Canc, Dept Oncol & Pathol, Stockholm, Sweden.
[Kanetsky, Peter A.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Ghiorzo, Paola] Univ Genoa, Dept Internal Med & Med Specialties, Genoa, Italy.
[Gruis, Nelleke A.] Leiden Univ, Med Ctr, Dept Dermatol, Leiden, Netherlands.
[Dwyer, Terry] Royal Childrens Hosp, Murdoch Childrens Res Inst, Parkville, Vic, Australia.
[Blizzard, Leigh] Univ Tasmania, Menzies Res Inst Tasmania, Hobart, Tas, Australia.
[Fernandez-de-Misa, Ricardo] Hosp Univ Nuestra Senora Candelaria, Serv Dermatol, Santa Cruz De Tenerife, Spain.
[Branicki, Wojciech] Inst Forens Res, Krakow, Poland.
[Debniak, Tadeusz] Pomeranian Med Univ, Dept Genet & Pathol, Polabska, Poland.
[Morling, Niels] Univ Copenhagen, Dept Forest Med, DK-1123 Copenhagen, Denmark.
[Landi, Maria Teresa] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Palmieri, Giuseppe] CNR, Ist Chim Biomol, Unit Canc Genet, Sassari, Italy.
[Ribas, Gloria] Fdn Investigat Hosp Clinico Univ Valencia, Dptd Oncol Med & Hematol, Valencia, Spain.
[Stratigos, Alexander] Univ Athens, Andreas Sygros Hosp, Dept Dermatol, Athens, Greece.
[Cornelius, Lynn] Washington Univ, Dept Dermatol, St Louis, MO USA.
[Motokawa, Tomonori] POLA Chem Ind, Dermatol R&D Skin Res Dept, Yokohama, Kanagawa, Japan.
[Anno, Sumiko] Shibaura Inst Technol, Tokyo 108, Japan.
[Helsing, Per] Oslo Univ Hosp, Dept Dermatol, Oslo, Norway.
[Wong, Terence H.] Univ Edinburgh, Dept Dermatol, Edinburgh, Midlothian, Scotland.
[Autier, Philippe] Int Prevent Res Inst, Lyon, France.
[Garcia-Borron, Jose C.] Univ Murcia, Dept Biochem & Mol Biol, Murcia, Spain.
[Little, Julian] Univ Ottawa, Dept Epidemiol & Community Hlth, Ottawa, ON, Canada.
[Newton-Bishop, Julia] Univ Leeds, Leeds Inst Mol Med, Sect Epidemiol & Biostat, Leeds, W Yorkshire, England.
[Sera, Francesco] UCL, Inst Child Hlth, London, England.
[Liu, Fan; Kayser, Manfred] Erasmus MC Univ Med Ctr, Dept Forens Mol Biol, Rotterdam, Netherlands.
[Nijsten, Tamar] Erasmus MC Univ Med Ctr, Dept Dermatol, Rotterdam, Netherlands.
RP Raimondi, S (reprint author), European Inst Oncol, Div Epidemiol & Biostat, Via Ramusio 1, I-20141 Milan, Italy.
EM sara.raimondi@ieo.it
RI Sera, Francesco/C-8176-2011; Garcia-Borron, Jose Carlos/H-2247-2015;
Autier, Philippe/A-4402-2014; Raimondi, Sara/J-5236-2016; Liu,
Fan/B-8833-2013;
OI Palmieri, Giuseppe/0000-0002-4350-2276; Newton Bishop,
Julia/0000-0001-9147-6802; Gandini, Sara/0000-0002-1348-4548;
Maisonneuve, Patrick/0000-0002-5309-4704; Gruis,
Nelleke/0000-0002-5210-9150; Fargnoli, Maria
Concetta/0000-0002-7249-2556; Garcia-Borron, Jose
Carlos/0000-0002-9192-588X; Sacerdote, Carlotta/0000-0002-8008-5096;
Autier, Philippe/0000-0003-1538-5321; Raimondi,
Sara/0000-0003-4673-9049; Liu, Fan/0000-0001-9241-8161; Kumar,
Rajiv/0000-0002-6093-0395
FU Italian Association for Cancer Research [MFAG 11831]; National Cancer
Institute [R01 CA112243, R01 CA112243-05 S1]
FX The M-SKIP study was supported by the Italian Association for Cancer
Research [MFAG 11831]. The GEM study was supported by National Cancer
Institute [R01 CA112243, R01 CA112243-05 S1].
NR 114
TC 2
Z9 2
U1 0
U2 16
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2288
J9 BMC MED RES METHODOL
JI BMC Med. Res. Methodol.
PD AUG 3
PY 2012
VL 12
AR 116
DI 10.1186/1471-2288-12-116
PG 13
WC Health Care Sciences & Services
SC Health Care Sciences & Services
GA 040TP
UT WOS:000311347300001
PM 22862891
ER
PT J
AU Rios-Doria, E
Chatterjee, R
Zhao, JF
Rishi, V
Vinson, C
AF Rios-Doria, Eric
Chatterjee, Raghunath
Zhao, Jianfei
Rishi, Vikas
Vinson, Charles
TI Ubiquitin tagged dominant negative induces degradation of B-ZIP proteins
SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
LA English
DT Article
DE B-ZIP domain; Ubiquitin; Trans; A-ZIP; Dominant negative
ID DNA-BINDING; INHIBITION
AB B-ZIP transcription factors heterodimerize with dominant negative designs, termed A-ZIPs, in a dimerization specific manner and inhibit its ability to bind DNA. Different A-ZIPs produce unique phenotypes in vivo suggesting that they have distinct B-ZIP heterodimerization partners. However, the identification of the in vivo heterodimerization partners of different A-ZIPs remains problematic. To identify the in vivo heterodimerization partners, a chimeric protein containing two ubiquitin motifs at the N-terminal of the A-ZIP domain was designed. The presence of ubiquitin reduced the concentration of specific co-transfected B-ZIP proteins. The ubiquitin enhanced degradation of the B-ZIP heterodimeric partner is inhibited by the proteasome inhibitor MG-132. These ubiquitin tagged A-ZIP dominant negatives may be more active in vivo because their endogenous heterodimerization partners are degraded more efficiently. This may be a general strategy to identify protein interaction partners. Published by Elsevier Inc.
C1 [Rios-Doria, Eric; Chatterjee, Raghunath; Zhao, Jianfei; Rishi, Vikas; Vinson, Charles] NCI, Lab Metab, NIH, Bethesda, MD 20892 USA.
RP Vinson, C (reprint author), NCI, Lab Metab, NIH, Bldg 37,Room 3128, Bethesda, MD 20892 USA.
EM Vinsonc@mail.nih.gov
NR 19
TC 0
Z9 0
U1 0
U2 1
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0006-291X
J9 BIOCHEM BIOPH RES CO
JI Biochem. Biophys. Res. Commun.
PD AUG 3
PY 2012
VL 424
IS 3
BP 624
EP 628
DI 10.1016/j.bbrc.2012.07.007
PG 5
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 990GK
UT WOS:000307618800045
PM 22789849
ER
PT J
AU Rounbehler, RJ
Fallahi, M
Yang, CY
Steeves, MA
Li, WM
Doherty, JR
Schaub, FX
Sanduja, S
Dixon, DA
Blackshear, PJ
Cleveland, JL
AF Rounbehler, Robert J.
Fallahi, Mohammad
Yang, Chunying
Steeves, Meredith A.
Li, Weimin
Doherty, Joanne R.
Schaub, Franz X.
Sanduja, Sandhya
Dixon, Dan A.
Blackshear, Perry J.
Cleveland, John L.
TI Tristetraprolin Impairs Myc-Induced Lymphoma and Abolishes the Malignant
State
SO CELL
LA English
DT Article
ID MESSENGER-RNA STABILITY; ELEMENT-BINDING PROTEIN; AU-RICH ELEMENTS;
C-MYC; BURKITT-LYMPHOMA; CANCER-CELLS; TRANSCRIPTION FACTOR; TRANSGENIC
MICE; GENE; EXPRESSION
AB Myc oncoproteins directly regulate transcription by binding to target genes, yet this only explains a fraction of the genes affected by Myc. mRNA turnover is controlled via AU-binding proteins (AUBPs) that recognize AU-rich elements (AREs) found within many transcripts. Analyses of precancerous and malignant Myc-expressing B cells revealed that Myc regulates hundreds of ARE-containing (ARED) genes and select AUBPs. Notably, Myc directly suppresses transcription of Tristetraprolin (TTP/ZFP36), an mRNA-destabilizing AUBP, and this circuit is also operational during B lymphopoiesis and IL7 signaling. Importantly, TTP suppression is a hallmark of cancers with MYC involvement, and restoring TTP impairs Myc-induced lymphomagenesis and abolishes maintenance of the malignant state. Further, there is a selection for TTP loss in malignancy; thus, TTP functions as a tumor suppressor. Finally, Myc/TTP-directed control of select cancer-associated ARED genes is disabled during lymphomagenesis. Thus, Myc targets AUBPs to regulate ARED genes that control tumorigenesis.
C1 [Rounbehler, Robert J.; Fallahi, Mohammad; Yang, Chunying; Steeves, Meredith A.; Li, Weimin; Doherty, Joanne R.; Schaub, Franz X.; Cleveland, John L.] Scripps Florida, Scripps Res Inst, Dept Canc Biol, Jupiter, FL 33458 USA.
[Sanduja, Sandhya; Dixon, Dan A.] Univ S Carolina, Dept Biol Sci, Columbia, SC 29208 USA.
[Sanduja, Sandhya; Dixon, Dan A.] Univ S Carolina, Ctr Colon Canc Res, Columbia, SC 29208 USA.
[Blackshear, Perry J.] NIEHS, Lab Signal Transduct, Res Triangle Pk, NC 27709 USA.
RP Cleveland, JL (reprint author), Scripps Florida, Scripps Res Inst, Dept Canc Biol, Jupiter, FL 33458 USA.
EM jcleve@scripps.edu
FU NIH [DK44158, CA167093, F32-CA115075, CA134609]; ThinkPink Kids
Foundation; State of Florida; NIH, NIEHS; National City Postdoctoral
Fellowship; Glenn W. Bailey Postdoctoral Fellowship; PGA National
Women's Cancer Foundation
FX We thank Jerry Adams for providing the pE mu SR alpha plasmid; Mihaela
Onciu and John Sandlund for providing Burkitt lymphoma samples; J. Alan
Diehl for providing MSCV-cyclin D1a retrovirus; Thomas Saunders and the
Transgenic Animal Model Core of the University of Michigan's Biomedical
Research Core Facilities for generating the E mu-TTP and E mu-Tis11b
transgenics; Wi Lai and Deborah Stumpo for technical assistance; Shannon
Sunday of the Scripps Florida ARC for assistance; Brandon Young and Brad
Long of the Scripps Florida Genomics Core; Bivian Torres and Kim Lowe of
the Scripps Florida Flow Cytometry Core; Frank C. Dorsey for helpful
discussions; and Marika Kernick for editing. This work was supported by
NIH grants (DK44158 and CA167093 to J. L. C., F32-CA115075 to R. J. R.
and CA134609 to D. A. D.), by monies from the ThinkPink Kids Foundation,
and by monies from the State of Florida to TSRI. P. J. B. is supported
by the Intramural Research Program of the NIH, NIEHS. R. J. R. also
received support from the National City Postdoctoral Fellowship, the
Glenn W. Bailey Postdoctoral Fellowship, and the PGA National Women's
Cancer Foundation.
NR 49
TC 39
Z9 39
U1 0
U2 7
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0092-8674
J9 CELL
JI Cell
PD AUG 3
PY 2012
VL 150
IS 3
BP 563
EP 574
DI 10.1016/j.cell.2012.06.033
PG 12
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 985WO
UT WOS:000307301400015
PM 22863009
ER
PT J
AU Bianchi, L
Gagliardi, A
Gioia, R
Besio, R
Tani, C
Landi, C
Cipriano, M
Gimigliano, A
Rossi, A
Marini, JC
Forlino, A
Bini, L
AF Bianchi, Laura
Gagliardi, Assunta
Gioia, Roberta
Besio, Roberta
Tani, Chiara
Landi, Claudia
Cipriano, Maria
Gimigliano, Anna
Rossi, Antonio
Marini, Joan C.
Forlino, Antonella
Bini, Luca
TI Differential response to intracellular stress in the skin from
osteogenesis imperfecta Brtl mice with lethal and non lethal phenotype:
A proteomic approach
SO JOURNAL OF PROTEOMICS
LA English
DT Article
DE Functional proteomics; Pathway analysis; Hierarchical clustering;
Osteogenesis imperfecta; Chaperones; Proteasomal
ID COLLAGEN MUTATION DATABASE; IMMOBILIZED PH GRADIENTS; EMBRYONIC
STEM-CELLS; I COLLAGEN; 2-DIMENSIONAL ELECTROPHORESIS;
ENDOPLASMIC-RETICULUM; POLYACRYLAMIDE-GELS; MOUSE MODEL; ER STRESS;
MISFOLDED PROCOLLAGEN
AB Phenotypic variability in the presence of an identical molecular defect is a recurrent feature in heritable disorders and it was also reported in osteogenesis imperfecta (01). OI is a prototype for skeletal dysplasias mainly caused by mutations in the two genes coding for type I collagen. No definitive cure is available for this disorder, but the understanding of molecular basis in 01 phenotypic modulation will have a pivotal role in identifying possible targets to develop novel drug therapy.
We used a functional proteomic approach to address the study of phenotypic variability using the skin of the 01 murine model Brtl. Brtl mice reproduce the molecular defect, dominant transmission and phenotypic variability of human OI patients. In the presence of a Gly349Cys substitution in alpha 1(I)-collagen Brtl mice can have a lethal or a moderately severe outcome.
Differential expression of chaperones, proteasomal subunits, metabolic enzymes, and proteins related to cellular fate demonstrated that a different ability to adapt to cellular stress distinguished mutant from wild-type mice and mutant lethal from surviving mutant animals. Interestingly, class discovery analysis identified clusters of differentially expressed proteins associated with a specific outcome, and functional analysis contributed to a deeper investigation into biochemical and cellular pathways affected by the disease. This article is part of a Special Issue entitled: Translational Proteomics. (C) 2012 Elsevier B.V. All rights reserved.
C1 [Gioia, Roberta; Besio, Roberta; Rossi, Antonio; Forlino, Antonella] Univ Pavia, Dept Mol Med, I-27100 Pavia, Italy.
[Bianchi, Laura; Gagliardi, Assunta; Cipriano, Maria; Gimigliano, Anna; Bini, Luca] Univ Siena, Sect Biochem & Mol Biol, Dept Biotechnol, Funct Prote Lab, I-53100 Siena, Italy.
[Tani, Chiara] Novartis Vaccines & Diagnost, Siena, Italy.
[Landi, Claudia] Univ Siena, Dept Clin Med & Immunol Sci, I-53100 Siena, Italy.
[Marini, Joan C.] NICHD, Bone & Extracellular Matrix Branch, NIH, Bethesda, MD USA.
RP Forlino, A (reprint author), Univ Pavia, Dept Mol Med, Via Taramelli 3-B, I-27100 Pavia, Italy.
EM aforlino@unipv.it
RI Rossi, Antonio/E-9935-2012; Forlino, Antonella/H-5385-2015;
OI Forlino, Antonella/0000-0002-6385-1182; landi,
claudia/0000-0003-0410-8038; Bini, Luca/0000-0001-8951-2106
FU PRIN [2008XA48SC]; Fondazione Cariplo; Progetto Regione Lombardia "Dalla
scienza dei materiali alla medicina mole-colare" [SAL/45]; FIRB project
"Italian Human ProteomeNet" [BRN07BMCT_013-MIUR]
FX This work was supported by PRIN 2008 (2008XA48SC), by Fondazione Cariplo
2007 and by Progetto Regione Lombardia (cod. SAL/45) "Dalla scienza dei
materiali alla medicina mole-colare" to Antonella For lino, and by the
FIRB project "Italian Human ProteomeNet" (BRN07BMCT_013-MIUR) to Luca
Bini.
NR 60
TC 4
Z9 4
U1 0
U2 8
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1874-3919
EI 1876-7737
J9 J PROTEOMICS
JI J. Proteomics
PD AUG 3
PY 2012
VL 75
IS 15
BP 4717
EP 4733
DI 10.1016/j.jprot.2012.01.038
PG 17
WC Biochemical Research Methods
SC Biochemistry & Molecular Biology
GA 990CV
UT WOS:000307609500015
PM 22846432
ER
PT J
AU Liu, T
Hossain, M
Schepmoes, AA
Fillmore, TL
Sokoll, LJ
Kronewitter, SR
Izmirlian, G
Shi, TJ
Qian, WJ
Leach, RJ
Thompson, IM
Chan, DW
Smith, RD
Kagan, J
Srivastava, S
Rodland, KD
Camp, DG
AF Liu, Tao
Hossain, Mahmud
Schepmoes, Athena A.
Fillmore, Thomas L.
Sokoll, Lori J.
Kronewitter, Scott R.
Izmirlian, Grant
Shi, Tujin
Qian, Wei-Jun
Leach, Robin J.
Thompson, Ian M.
Chan, Daniel W.
Smith, Richard D.
Kagan, Jacob
Srivastava, Sudhir
Rodland, Karin D.
Camp, David G., II
TI Analysis of serum total and free PSA using immunoaffinity depletion
coupled to SRM: correlation with clinical immunoassay tests
SO JOURNAL OF PROTEOMICS
LA English
DT Article
DE Selected reaction monitoring; Immunoaffinity depletion; Total PSA; Free
PSA; Serum; Immunoassay
ID PROSTATE-SPECIFIC ANTIGEN; MEDICINE PRACTICE GUIDELINES;
MASS-SPECTROMETRY; NATIONAL ACADEMY; PLASMA-PROTEINS; TUMOR-MARKERS;
GENE FUSIONS; CANCER; QUANTITATION; MULTICENTER
AB Recently, selected reaction monitoring mass spectrometry (SRM-MS) has been more frequently applied to measure low abundance biomarker candidates in tissues and biofluids, owing to its high sensitivity and specificity, simplicity of assay configuration, and exceptional multiplexing capability. In this study, we report for the first time the development of immunoaffinity depletion-based workflows and SRM-MS assays that enable sensitive and accurate quantification of total and free prostate-specific antigen (PSA) in serum without the requirement for specific PSA antibodies. Low ng/mL level detection of both total and free PSA was consistently achieved in both PSA-spiked female serum samples and actual patient serum samples. Moreover, comparison of the results obtained when SRM PSA assays and conventional immunoassays were applied to the same samples showed good correlation in several independent clinical serum sample sets. These results demonstrate that the workflows and SRM assays developed here provide an attractive alternative for reliably measuring candidate biomarkers in human blood, without the need to develop affinity reagents. Furthermore, the simultaneous measurement of multiple biomarkers, including the free and bound forms of PSA, can be performed in a single multiplexed analysis using high-resolution liquid chromatographic separation coupled with SRM-MS. This article is part of a Special Issue entitled: Translational Proteomics. (C) 2012 Elsevier B.V. All rights reserved.
C1 [Liu, Tao; Hossain, Mahmud; Schepmoes, Athena A.; Fillmore, Thomas L.; Kronewitter, Scott R.; Shi, Tujin; Qian, Wei-Jun; Smith, Richard D.; Rodland, Karin D.; Camp, David G., II] Pacific NW Natl Lab, Div Biol Sci, Richland, WA 99354 USA.
[Sokoll, Lori J.; Chan, Daniel W.] Johns Hopkins Med Inst, Dept Pathol, Baltimore, MD USA.
[Sokoll, Lori J.; Chan, Daniel W.] Johns Hopkins Med Inst, Dept Urol, Baltimore, MD USA.
[Izmirlian, Grant; Kagan, Jacob; Srivastava, Sudhir] NCI, Canc Prevent Div, Bethesda, MD 20892 USA.
[Leach, Robin J.; Thompson, Ian M.] Univ Texas Hlth Sci Ctr San Antonio, Dept Urol, San Antonio, TX USA.
RP Camp, DG (reprint author), Pacific NW Natl Lab, Div Biol Sci, POB 999,MSIN K8-98, Richland, WA 99354 USA.
EM dave.camp@pnnl.gov
RI Smith, Richard/J-3664-2012; Liu, Tao/A-9020-2013; Shi, Tujin/O-1789-2014
OI Smith, Richard/0000-0002-2381-2349; Liu, Tao/0000-0001-9529-6550;
FU National Cancer Institute Early Detection Research Network Interagency
[Y01-CN-05013-29]; National Institutes of Health [P41 RR018522, U01
CA115102, U01 CA86402, P30 CA054174-18]; Department of Energy
[DE-AC05-76RL0 1830]
FX Portions of this work were supported by the National Cancer Institute
Early Detection Research Network Interagency Agreement Y01-CN-05013-29
(to K.D.R. and D.G.C.) and National Institutes of Health Grants P41
RR018522 (to R.D.S.), U01 CA115102 (to D.W.C.), and U01 CA86402 and P30
CA054174-18 (to I.M.T). The experimental work described herein was
performed in the Environmental Molecular Sciences Laboratory, a national
scientific user facility sponsored by the Department of Energy and
located at Pacific Northwest National Laboratory, which is operated by
Battelle Memorial Institute for the Department of Energy under Contract
DE-AC05-76RL0 1830.
NR 36
TC 31
Z9 31
U1 0
U2 18
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1874-3919
J9 J PROTEOMICS
JI J. Proteomics
PD AUG 3
PY 2012
VL 75
IS 15
BP 4747
EP 4757
DI 10.1016/j.jprot.2012.01.035
PG 11
WC Biochemical Research Methods
SC Biochemistry & Molecular Biology
GA 990CV
UT WOS:000307609500017
PM 22846433
ER
PT J
AU Pereira, L
Zamudio, R
Soares-Souza, G
Herrera, P
Cabrera, L
Hooper, CC
Cok, J
Combe, JM
Vargas, G
Prado, WA
Schneider, S
Kehdy, F
Rodrigues, MR
Chanock, SJ
Berg, DE
Gilman, RH
Tarazona-Santos, E
AF Pereira, Latife
Zamudio, Roxana
Soares-Souza, Giordano
Herrera, Phabiola
Cabrera, Lilia
Hooper, Catherine C.
Cok, Jaime
Combe, Juan M.
Vargas, Gloria
Prado, William A.
Schneider, Silvana
Kehdy, Fernanda
Rodrigues, Maira R.
Chanock, Stephen J.
Berg, Douglas E.
Gilman, Robert H.
Tarazona-Santos, Eduardo
TI Socioeconomic and Nutritional Factors Account for the Association of
Gastric Cancer with Amerindian Ancestry in a Latin American Admixed
Population
SO PLOS ONE
LA English
DT Article
ID SQUAMOUS-CELL CARCINOMA; HELICOBACTER-PYLORI; RISK; ESOPHAGEAL;
ADENOCARCINOMA; PATTERNS; SUSCEPTIBILITY; PREVALENCE; ADMIXTURE;
DISEASES
AB Gastric cancer is one of the most lethal types of cancer and its incidence varies worldwide, with the Andean region of South America showing high incidence rates. We evaluated the genetic structure of the population from Lima (Peru) and performed a case-control genetic association study to test the contribution of African, European, or Native American ancestry to risk for gastric cancer, controlling for the effect of non-genetic factors. A wide set of socioeconomic, dietary, and clinic information was collected for each participant in the study and ancestry was estimated based on 103 ancestry informative markers. Although the urban population from Lima is usually considered as mestizo (i.e., admixed from Africans, Europeans, and Native Americans), we observed a high fraction of Native American ancestry (78.4% for the cases and 74.6% for the controls) and a very low African ancestry (<5%). We determined that higher Native American individual ancestry is associated with gastric cancer, but socioeconomic factors associated both with gastric cancer and Native American ethnicity account for this association. Therefore, the high incidence of gastric cancer in Peru does not seem to be related to susceptibility alleles common in this population. Instead, our result suggests a predominant role for ethnic-associated socioeconomic factors and disparities in access to health services. Since Native Americans are a neglected group in genomic studies, we suggest that the population from Lima and other large cities from Western South America with high Native American ancestry background may be convenient targets for epidemiological studies focused on this ethnic group.
C1 [Pereira, Latife; Zamudio, Roxana; Soares-Souza, Giordano; Kehdy, Fernanda; Rodrigues, Maira R.] Univ Fed Minas Gerais, Dept Biol Geral, Belo Horizonte, MG, Brazil.
[Herrera, Phabiola; Cabrera, Lilia; Gilman, Robert H.; Tarazona-Santos, Eduardo] Asociac Benef PRISMA, Lima, Peru.
[Hooper, Catherine C.; Gilman, Robert H.] Univ Peruana Cayetano Heredia, Fac Ciencias, Lab Invest & Desarrollo, Lima, Peru.
[Cok, Jaime] Hosp Nacl Cayetano Heredia, Dept Patol, Lima, Peru.
[Combe, Juan M.] Inst Nacl Engermedades Neoplascas, Dept Gastroenterol, Lima, Peru.
[Vargas, Gloria] Hosp Nacl Arzobispo Loayza, Serv Gastroenterol, Lima, Peru.
[Prado, William A.] Hosp Dos de Mayo, Serv Gastroenterol, Lima, Peru.
[Schneider, Silvana] Univ Fed Minas Gerais, Dept Estat, Belo Horizonte, MG, Brazil.
[Chanock, Stephen J.] NCI, Lab Translat Genom, Div Canc Epidemiol & Genet, NIH, Gaithersburg, MD USA.
[Berg, Douglas E.] Washington Univ, Sch Med, Dept Mol Microbiol, St Louis, MO 63110 USA.
[Gilman, Robert H.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Int Hlth, Baltimore, MD USA.
RP Pereira, L (reprint author), Univ Fed Minas Gerais, Dept Biol Geral, Belo Horizonte, MG, Brazil.
EM edutars@icb.ufmg.br
FU Fogarty International Center and National Cancer Institute
[5R01TW007894]; Brazilian National Research Council; Ministry of
Education; Ministry of Health (PNPD-Saude Program); Minas Gerais State
Reaearch Agency
FX Fogarty International Center and National Cancer Institute
(5R01TW007894) funded this study. The study and its participants also
received funding and fellowships from the following Brazilian agencies:
Brazilian National Research Council, Ministry of Education, Ministry of
Health (PNPD-Saude Program), and the Minas Gerais State Reaearch Agency.
The funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 45
TC 13
Z9 13
U1 0
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 3
PY 2012
VL 7
IS 8
AR e41200
DI 10.1371/journal.pone.0041200
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 985QT
UT WOS:000307284100013
PM 22870209
ER
PT J
AU Saini, V
Hose, CD
Monks, A
Nagashima, K
Han, BN
Newton, DL
Millione, A
Shah, J
Hollingshead, MG
Hite, KM
Burkett, MW
Delosh, RM
Silvers, TE
Scudiero, DA
Shoemaker, RH
AF Saini, Vaibhav
Hose, Curtis D.
Monks, Anne
Nagashima, Kunio
Han, Bingnan
Newton, Dianne L.
Millione, Angelena
Shah, Jalpa
Hollingshead, Melinda G.
Hite, Karen M.
Burkett, Mark W.
Delosh, Rene M.
Silvers, Thomas E.
Scudiero, Dominic A.
Shoemaker, Robert H.
TI Identification of CBX3 and ABCA5 as Putative Biomarkers for Tumor Stem
Cells in Osteosarcoma
SO PLOS ONE
LA English
DT Article
ID PROSTATE-CANCER CELLS; ALDEHYDE DEHYDROGENASE; LUNG-CANCER; OSTEOBLASTIC
PROPERTIES; INITIATING CELLS; DRUG-RESISTANCE; LINE SAOS-2; EXPRESSION;
MARKER; OCT-4
AB Recently, there has been renewed interest in the role of tumor stem cells (TSCs) in tumorigenesis, chemoresistance, and relapse of malignant tumors including osteosarcoma. The potential exists to improve osteosarcoma treatment through characterization of TSCs and identification of therapeutic targets. Using transcriptome, proteome, immunophenotyping for cell-surface markers, and bioinformatic analyses, heterogeneous expression of previously reported TSC or osteosarcoma markers, such as CD133, nestin, POU5F1 (OCT3/4), NANOG, SOX2, and aldehyde dehydrogenase, among others, was observed in vitro. However, consistently significantly lower CD326, CD24, CD44, and higher ABCG2 expression in TSC-enriched as compared with un-enriched osteosarcoma cultures was observed. In addition, consistently higher CBX3 expression in TSC-enriched osteosarcoma cultures was identified. ABCA5 was identified as a putative biomarker of TSCs and/or osteosarcoma. Lastly, in a high-throughput screen we identified epigenetic (5-azacytidine), anti-microtubule (vincristine), and anti-telomerase (3,11-difluoro-6,8,13-trimethyl-8H-quino [4,3,2-kl] acridinium methosulfate; RHPS4)-targeted therapeutic agents as candidates for TSC ablation in osteosarcoma.
C1 [Saini, Vaibhav; Shoemaker, Robert H.] NCI, Screening Technol Branch, Dev Therapeut Program, Div Canc Treatment & Diag, Frederick, MD 21701 USA.
[Hose, Curtis D.; Monks, Anne; Nagashima, Kunio; Han, Bingnan; Newton, Dianne L.; Millione, Angelena; Shah, Jalpa; Hite, Karen M.; Burkett, Mark W.; Delosh, Rene M.; Silvers, Thomas E.; Scudiero, Dominic A.] NCI, SAIC Frederick, Frederick, MD 21701 USA.
[Hollingshead, Melinda G.] NCI, Biol Testing Branch, Div Canc Treatment & Diag, Frederick, MD 21701 USA.
RP Saini, V (reprint author), Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA.
EM Shoemakr@mail.nih.gov
FU National Cancer Institute (NCI); National Institutes of Health (NIH);
Developmental Therapeutics Program in the Division of Cancer Treatment
and Diagnosis of the National Cancer Institute; NCI, NIH
[HHSN261200800001E]
FX VS was supported by a visiting fellowship, National Cancer Institute
(NCI), and National Institutes of Health (NIH). The research was
supported in part by the Developmental Therapeutics Program in the
Division of Cancer Treatment and Diagnosis of the National Cancer
Institute, and in part with federal funds from the NCI, NIH, under
contract HHSN261200800001E. The funders had no role in study design,
data collection and analysis, decision to publish, or preparation of the
manuscript.
NR 51
TC 31
Z9 34
U1 0
U2 10
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD AUG 3
PY 2012
VL 7
IS 8
AR e41401
DI 10.1371/journal.pone.0041401
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 985QT
UT WOS:000307284100017
PM 22870217
ER
PT J
AU Won, YJ
Ono, F
Ikeda, SR
AF Won, Yu-Jin
Ono, Fumihito
Ikeda, Stephen R.
TI Characterization of Na+ and Ca2+ Channels in Zebrafish Dorsal Root
Ganglion Neurons
SO PLOS ONE
LA English
DT Article
ID ROHON-BEARD NEURONS; VOLTAGE-DEPENDENT MODULATION; PROGRAMMED
CELL-DEATH; BETA-GAMMA-SUBUNITS; NERVE GROWTH-FACTOR; CALCIUM-CHANNELS;
SENSORY NEURONS; ADULT-RAT; IN-VIVO; N-TYPE
AB Background: Dorsal root ganglia (DRG) somata from rodents have provided an excellent model system to study ion channel properties and modulation using electrophysiological investigation. As in other vertebrates, zebrafish (Danio rerio) DRG are organized segmentally and possess peripheral axons that bifurcate into each body segment. However, the electrical properties of zebrafish DRG sensory neurons, as compared with their mammalian counterparts, are relatively unexplored because a preparation suitable for electrophysiological studies has not been available.
Methodology/Principal Findings: We show enzymatically dissociated DRG neurons from juvenile zebrafish expressing Isl2b-promoter driven EGFP were easily identified with fluorescence microscopy and amenable to conventional whole-cell patch-clamp studies. Two kinetically distinct TTX-sensitive Na+ currents (rapidly-and slowly-inactivating) were discovered. Rapidly-inactivating I-Na were preferentially expressed in relatively large neurons, while slowly-inactivating I-Na was more prevalent in smaller DRG neurons. RT-PCR analysis suggests zscn1aa/ab, zscn8aa/ab, zscn4ab and zscn5Laa are possible candidates for these I-Na components. Voltage-gated Ca2+ currents (I-Ca) were primarily (87%) comprised of a high-voltage activated component arising from v-conotoxin GVIA-sensitive Ca(V)2.2 (N-type) Ca2+ channels. A few DRG neurons (8%) displayed a miniscule low-voltage-activated component. I-Ca in zebrafish DRG neurons were modulated by neurotransmitters via either voltage-dependent or -independent G-protein signaling pathway with large cell-to-cell response variability.
Conclusions/Significance: Our present results indicate that, as in higher vertebrates, zebrafish DRG neurons are heterogeneous being composed of functionally distinct subpopulations that may correlate with different sensory modalities. These findings provide the first comparison of zebrafish and rodent DRG neuron electrical properties and thus provide a basis for future studies.
C1 [Won, Yu-Jin; Ikeda, Stephen R.] NIAAA, Sect Transmitter Signaling, Lab Mol Physiol, NIH, Bethesda, MD USA.
[Ono, Fumihito] NIAAA, Sect Model Synapt Syst, Lab Mol Physiol, NIH, Bethesda, MD USA.
RP Won, YJ (reprint author), NIAAA, Sect Transmitter Signaling, Lab Mol Physiol, NIH, Bethesda, MD USA.
EM sikeda@mail.nih.gov
OI Ikeda, Stephen/0000-0002-4088-9508
FU National Institutes of Health, National Institute on Alcohol Abuse and
Alcoholism
FX This work was supported by the intramural program at the National
Institutes of Health, National Institute on Alcohol Abuse and
Alcoholism. The funder had no role in study design, data collection and
analysis, decision to publish, or preparation of the manuscript.
NR 54
TC 1
Z9 1
U1 2
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 3
PY 2012
VL 7
IS 8
AR e42602
DI 10.1371/journal.pone.0042602
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 985QT
UT WOS:000307284100140
PM 22880050
ER
PT J
AU Ruffin, MT
Hade, EM
Gorsline, MR
DeGraffinreid, CR
Katz, ML
Kobrin, SC
Paskett, ED
AF Ruffin, Mack T.
Hade, Erinn M.
Gorsline, Melissa R.
DeGraffinreid, Cecilia R.
Katz, Mira L.
Kobrin, Sarah C.
Paskett, Electra D.
TI Human papillomavirus vaccine knowledge and hypothetical acceptance among
women in Appalachia Ohio
SO VACCINE
LA English
DT Article
DE Human papillomavirus; Papillomavirus vaccines; Women; Rural population;
Attitude to health
ID AGED 13-17 YEARS; HPV VACCINE; CERVICAL-CANCER; UNITED-STATES; ROCHE
AMPLICOR; PREDICTORS; ADOLESCENTS; ATTITUDES; PARENTS; VIRUS
AB Objective: To assess hypothetical acceptance of the human papillomavirus (HPV) vaccine for themselves and a daughter age 9-12 years among Appalachia Ohio women.
Methods: Women with an abnormal Pap smear and randomly selected women with a normal Pap smear from 17 clinics completed an interview in 2006-2008.
Results: From 1131 original study participants, 807 (71%) completed a survey about the HPV vaccine for their daughters and themselves. Nearly half, 380 (47%), of the participants had heard of a vaccine to prevent cancer, and 362 (95%) of respondents had heard of HPV. The participants were then told that the FDA had approved a vaccine to prevent HPV. Only 379 (38%) participants identified girls ages 9-12 years as a group who should get the vaccine. After being given the official HPV vaccine recommendation statement, 252 (31%) wanted the vaccine; 198 (25%) were "not sure"; and 353 (44%) did not want the vaccine for themselves. With respect to giving the HPV vaccine to a daughter ages 9-12 years, participants responded "yes" 445 (55%); "not sure" 163 (20%); or "no" 185 (23%). Numerous reasons were provided supporting and opposing vaccine acceptance for themselves and for a daughter. Their physician's recommendation for the HPV vaccine increased vaccine acceptance to 86% for themselves and 90% for a daughter.
Conclusion: Knowledge, acceptance, and barriers about the HPV vaccine vary among women living in Appalachia Ohio. Physician recommendation is a key facilitator for vaccine diffusion in this region. (C) 2012 Elsevier Ltd. All rights reserved.
C1 [Ruffin, Mack T.] Univ Michigan, Dept Family Med, Ann Arbor, MI 48104 USA.
[Hade, Erinn M.] Ohio State Univ, Ctr Biostat, Columbus, OH 43221 USA.
[Paskett, Electra D.] Ohio State Univ, Ctr Comprehens Canc, Coll Med, Columbus, OH 43201 USA.
[Katz, Mira L.; Paskett, Electra D.] Ohio State Univ, Coll Publ Hlth, Columbus, OH 43201 USA.
[Kobrin, Sarah C.] NCI, Appl Canc Screening Res Branch, Behav Res Program, Div Canc Control & Populat Sci, Rockville, MD 20852 USA.
RP Ruffin, MT (reprint author), Univ Michigan, Dept Family Med, 1018 Fuller St, Ann Arbor, MI 48104 USA.
EM mruffin@umich.edu; Erinn.Hade@osumc.edu; lissarue@hotmail.com;
Cecilia.DeGraffinreid@osumc.edu; Mira.Katz@osumc.edu;
kobrins@mail.nih.gov; Electra.Paskett@osumc.edu
RI Katz, Mira/B-6957-2012;
OI Ruffin, Mack/0000-0001-8336-478X
FU National Institutes of Health [P50 CA105632]; Ohio State University
Comprehensive Cancer Center [P30 CA016058]; National Cancer Institute
[K07 CA107079]; National Center for Research Resources [UL1RR025755]
FX This work was supported by grant P50 CA105632 from the National
Institutes of Health. This study was also supported by the Behavioral
Measurement Shared Resource at The Ohio State University Comprehensive
Cancer Center (grant number P30 CA016058), K07 CA107079 (MLK) from the
National Cancer Institute, and the National Center for Research
Resources (UL1RR025755).
NR 41
TC 5
Z9 5
U1 2
U2 6
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0264-410X
J9 VACCINE
JI Vaccine
PD AUG 3
PY 2012
VL 30
IS 36
BP 5349
EP 5357
DI 10.1016/j.vaccine.2012.06.034
PG 9
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA 991KB
UT WOS:000307698800009
PM 22749839
ER
PT J
AU Suratt, BT
Fessler, MB
AF Suratt, Benjamin T.
Fessler, Michael B.
TI Greasing the Way: The ABCs of HSPC Efflux from the Marrow
SO CELL STEM CELL
LA English
DT Editorial Material
ID STEM-CELL PROLIFERATION; ACCUMULATION; HOMEOSTASIS; MICE
AB In this issue of Cell Stem Cell, Westerterp et al. demonstrate that cholesterol flux through splenic phagocytes regulates hematopoietic stem and multipotential progenitor cell mobilization from the bone marrow. These exciting findings suggest new avenues for therapy of myeloproliferative disorders and atherosclerosis.
C1 [Fessler, Michael B.] NIEHS, Lab Resp Biol, NIH, Res Triangle Pk, NC 27709 USA.
[Suratt, Benjamin T.] Univ Vermont, Coll Med, Vermont Lung Ctr, Burlington, VT 05405 USA.
RP Fessler, MB (reprint author), NIEHS, Lab Resp Biol, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.
EM fesslerm@niehs.nih.gov
FU Intramural NIH HHS [ZIA ES102005-06]; NHLBI NIH HHS [R01 HL084200];
NIGMS NIH HHS [P30 GM103532]
NR 9
TC 2
Z9 2
U1 0
U2 2
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1934-5909
J9 CELL STEM CELL
JI Cell Stem Cell
PD AUG 3
PY 2012
VL 11
IS 2
BP 143
EP 144
DI 10.1016/j.stem.2012.07.009
PG 2
WC Cell & Tissue Engineering; Cell Biology
SC Cell Biology
GA 987QQ
UT WOS:000307432600004
PM 22862939
ER
PT J
AU Li, XZ
Li, L
Pandey, R
Byun, JS
Gardner, K
Qin, ZH
Dou, YL
AF Li, Xiangzhi
Li, Li
Pandey, Ruchi
Byun, Jung S.
Gardner, Kevin
Qin, Zhaohui
Dou, Yali
TI The Histone Acetyltransferase MOF Is a Key Regulator of the Embryonic
Stem Cell Core Transcriptional Network
SO CELL STEM CELL
LA English
DT Article
ID SELF-RENEWAL; DOSAGE COMPENSATION; ES CELLS; CHROMATIN-STRUCTURE; H4-K16
ACETYLATION; PLURIPOTENCY; NANOG; DIFFERENTIATION; METHYLATION;
DROSOPHILA
AB Pluripotent embryonic stem cells (ESCs) maintain self-renewal and the potential for rapid response to differentiation cues. Both ESC features are subject to epigenetic regulation. Here we show that the histone acetyltransferase Mof plays an essential role in the maintenance of ESC self-renewal and pluripotency. ESCs with Mof deletion lose characteristic morphology, alkaline phosphatase (AP) staining, and differentiation potential. They also have aberrant expression of the core transcription factors Nanog, Oct4, and Sox2. Importantly, the phenotypes of Mof null ESCs can be partially suppressed by Nanog overexpression, supporting the idea that Mof functions as an upstream regulator of Nanog in ESCs. Genome-wide ChIP-sequencing and transcriptome analyses further demonstrate that Mof is an integral component of the ESC core transcriptional network and that Mof primes genes for diverse developmental programs. Mof is also required for Wdr5 recruitment and H3K4 methylation at key regulatory loci, highlighting the complexity and interconnectivity of various chromatin regulators in ESCs.
C1 [Li, Xiangzhi; Pandey, Ruchi; Dou, Yali] Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA.
[Dou, Yali] Univ Michigan, Dept Biol Chem, Ann Arbor, MI 48109 USA.
[Li, Xiangzhi] Shandong Univ, Sch Med, Inst Cell Biol, Jinan 250100, Shandong, Peoples R China.
[Li, Li; Qin, Zhaohui] Emory Univ, Rollins Sch Publ Hlth, Dept Biostat & Bioinformat, Atlanta, GA 30322 USA.
[Byun, Jung S.; Gardner, Kevin] NIH, Gene Express Lab, Bethesda, MD 20892 USA.
RP Dou, YL (reprint author), Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA.
EM yalid@umich.edu
RI Pandey, Ruchi/D-2882-2013;
OI Pandey, Ruchi/0000-0001-6417-0971; Qin, Zhaohui/0000-0002-1583-146X
FU NIGMS [R01GM082856]; American Cancer Society [RSG 117573]; NHGRI
[R01HG005119]; NSFC [31171428]
FX We thank Dr. Yi Zhang for the anti-Nanog antibody and the Nanog
expression vector. This work is supported by NIGMS (R01GM082856) and
American Cancer Society (RSG 117573) grants to Y.D., NHGRI (R01HG005119)
grant to Z.Q., and NSFC (31171428) grant to X.L.
NR 53
TC 61
Z9 65
U1 3
U2 28
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1934-5909
J9 CELL STEM CELL
JI Cell Stem Cell
PD AUG 3
PY 2012
VL 11
IS 2
BP 163
EP 178
DI 10.1016/j.stem.2012.04.023
PG 16
WC Cell & Tissue Engineering; Cell Biology
SC Cell Biology
GA 987QQ
UT WOS:000307432600008
PM 22862943
ER
PT J
AU Daee, DL
Ferrari, E
Longerich, S
Zheng, XF
Xue, XY
Branzei, D
Sung, P
Myung, K
AF Daee, Danielle L.
Ferrari, Elisa
Longerich, Simonne
Zheng, Xiao-feng
Xue, Xiaoyu
Branzei, Dana
Sung, Patrick
Myung, Kyungjae
TI Rad5-dependent DNA Repair Functions of the Saccharomyces cerevisiae
FANCM Protein Homolog Mph1
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID INTERSTRAND CROSS-LINKS; CELL NUCLEAR ANTIGEN; FREE POSTREPLICATION
REPAIR; STALLED REPLICATION FORKS; STRAND BREAK REPAIR; GROSS
CHROMOSOMAL REARRANGEMENTS; NUCLEOTIDE EXCISION-REPAIR; UBIQUITIN
LIGASE; RAD6 PATHWAY; ERROR-PRONE
AB Interstrand cross-links (ICLs) covalently link complementary DNA strands, block DNA replication, and transcription and must be removed to allow cell survival. Several pathways, including the Fanconi anemia (FA) pathway, can faithfully repair ICLs and maintain genomic integrity; however, the precise mechanisms of most ICL repair processes remain enigmatic. In this study we genetically characterized a conserved yeast ICL repair pathway composed of the yeast homologs (Mph1, Chl1, Mhf1, Mhf2) of four FA proteins (FANCM, FANCJ, MHF1, MHF2). This pathway is epistatic with Rad5-mediated DNA damage bypass and distinct from the ICL repair pathways mediated by Rad18 and Pso2. In addition, consistent with the FANCM role in stabilizing ICL-stalled replication forks, we present evidence that Mph1 prevents ICL-stalled replication forks from collapsing into double-strand breaks. This unique repair function of Mph1 is specific for ICL damage and does not extend to other types of damage. These studies reveal the functional conservation of the FA pathway and validate the yeast model for future studies to further elucidate the mechanism of the FA pathway.
C1 [Daee, Danielle L.; Myung, Kyungjae] NHGRI, Genome Instabil Sect, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA.
[Ferrari, Elisa; Branzei, Dana] Fdn IFOM, Ist FIRC Oncol Mol, I-20139 Milan, Italy.
[Longerich, Simonne; Zheng, Xiao-feng; Xue, Xiaoyu; Sung, Patrick] Yale Univ, Dept Mol Biophys & Biochem, Sch Med, New Haven, CT 06520 USA.
RP Myung, K (reprint author), NHGRI, Genome Instabil Sect, Genet & Mol Biol Branch, NIH, 49 Convent Dr, Bethesda, MD 20892 USA.
EM kmyung@mail.nih.gov
RI xue, xiaoyu/G-9574-2012; Branzei, Dana/A-2806-2015
OI Branzei, Dana/0000-0002-0544-4888
FU National Institutes of Health Grant [HG012003-09]; European Research
Council Grant [REPSUBREP 242928]; Associazione Italiana per la Ricerca
sul Cancuro Grant [IG 10637]
FX This work was supported, in whole or in part, by National Institutes of
Health Grant HG012003-09 (National Human Genome Research Institute; to
K. M.). This work was also supported by European Research Council Grant
REPSUBREP 242928 and Associazione Italiana per la Ricerca sul Cancuro
Grant IG 10637 (to D. B.).
NR 90
TC 15
Z9 15
U1 0
U2 3
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD AUG 3
PY 2012
VL 287
IS 32
BP 26563
EP 26575
DI 10.1074/jbc.M112.369918
PG 13
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 986ZK
UT WOS:000307386000009
PM 22696213
ER
PT J
AU Arora, G
Sajid, A
Arulanandh, MD
Singhal, A
Mattoo, AR
Pomerantsev, AP
Leppla, SH
Maiti, S
Singh, Y
AF Arora, Gunjan
Sajid, Andaleeb
Arulanandh, Mary Diana
Singhal, Anshika
Mattoo, Abid R.
Pomerantsev, Andrei P.
Leppla, Stephen H.
Maiti, Souvik
Singh, Yogendra
TI Unveiling the Novel Dual Specificity Protein Kinases in Bacillus
anthracis IDENTIFICATION OF THE FIRST PROKARYOTIC DUAL SPECIFICITY
TYROSINE PHOSPHORYLATION-REGULATED KINASE (DYRK)-LIKE KINASE
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID BACILLUS-SUBTILIS; TYROSINE KINASE; MYCOBACTERIUM-TUBERCULOSIS;
SIGNAL-TRANSDUCTION; ESCHERICHIA-COLI; SERINE/THREONINE KINASES;
ACTIVATION MECHANISM; PHYSIOLOGICAL ROLES; PYRUVATE KINASES; DYRK FAMILY
AB Dual specificity protein kinases (DSPKs) are unique enzymes that can execute multiple functions in the cell, which are otherwise performed exclusively by serine/threonine and tyrosine protein kinases. In this study, we have characterized the protein kinases Bas2152 (PrkD) and Bas2037 (PrkG) from Bacillus anthracis. Transcriptional analyses of these kinases showed that they are expressed in all phases of growth. In a serendipitous discovery, both kinases were found to be DSPKs. PrkD was found to be similar to the eukaryotic dual specificity Tyr phosphorylation-regulated kinase class of dual specificity kinases, which autophosphorylates on Ser, Thr, and Tyr residues and phosphorylates Ser and Thr residues on substrates. PrkG was found to be a bona fide dual specificity protein kinase that mediates autophosphorylation and substrate phosphorylation on Ser, Thr, and Tyr residues. The sites of phosphorylation in both of the kinases were identified through mass spectrometry. Phosphorylation on Tyr residues regulates the kinase activity of PrkD and PrkG. PrpC, the only known Ser/Thr protein phosphatase, was also found to possess dual specificity. Genistein, a known Tyr kinase inhibitor, was found to inhibit the activities of PrkD and PrkG and affect the growth of B. anthracis cells, indicating a possible role of these kinases in cell growth and development. In addition, the glycolytic enzyme pyruvate kinase was found to be phosphorylated by PrkD on Ser and Thr residues but not by PrkG. Thus, this study provides the first evidence of DSPKs in B. anthracis that belong to different classes and have different modes of regulation.
C1 [Arora, Gunjan; Sajid, Andaleeb; Arulanandh, Mary Diana; Singhal, Anshika; Mattoo, Abid R.; Maiti, Souvik; Singh, Yogendra] Inst Genom & Integrat Biol, Council Sci & Ind Res, Delhi 110007, India.
[Pomerantsev, Andrei P.; Leppla, Stephen H.] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Singh, Y (reprint author), Inst Genom & Integrat Biol, Council Sci & Ind Res, Mall Rd, Delhi 110007, India.
EM ysingh@igib.res.in
RI Ganju, Shahji/F-3409-2012;
OI Sajid, Andaleeb/0000-0001-6248-4985; MATTOO, ABID/0000-0002-4947-0113
FU National Institutes of Health, NIAID, Intramural Research Program;
Council of Scientific and Industrial Research Grant [NWP-0038]
FX This work was supported, in whole or in part, by the National Institutes
of Health, NIAID, Intramural Research Program. This work was also
supported by Council of Scientific and Industrial Research Grant
NWP-0038.
NR 77
TC 14
Z9 14
U1 1
U2 8
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD AUG 3
PY 2012
VL 287
IS 32
BP 26749
EP 26763
DI 10.1074/jbc.M112.351304
PG 15
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 986ZK
UT WOS:000307386000025
PM 22711536
ER
PT J
AU Takayama, Y
Clore, GM
AF Takayama, Yuki
Clore, G. Marius
TI Impact of Protein/Protein Interactions on Global Intermolecular
Translocation Rates of the Transcription Factors Sox2 and Oct1 between
DNA Cognate Sites Analyzed by z-Exchange NMR Spectroscopy
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID PARAMAGNETIC RELAXATION ENHANCEMENT; CHEMICAL-EXCHANGE; HETERONUCLEAR
CORRELATION; CRYSTAL-STRUCTURE; POU DOMAIN; BINDING; COMPLEXES;
ACTIVATION; HOMEODOMAIN; PROTEINS
AB Oct1 and Sox2 synergistically regulate developmental genes by binding to adjacent sites within promoters. We have investigated the kinetics of global intermolecular translocation of Sox2 and Oct1 between cognate sites located on different DNA molecules by z-exchange NMR spectroscopy. In the Hoxb1 promoter, the Sox2 and Oct1 sites are immediately adjacent to one another, and the intermolecular translocation rates are too slow to be measured by z-exchange spectroscopy. By introducing a 3-bp insertion between the Sox2 and Oct1 sites to mimic the spacing in the FGF4 enhancer, the interprotein contact surface is reduced, and the translocation rates are increased. Interaction between Sox2 and the POU-specific domain (POUS) of Oct1 does not affect the translocation mechanism but modulates the rates. Translocation involves only jumping (dissociation and reassociation) for Sox2, but both jumping and direct intersegment transfer (no dissociation into free solution) for Oct1. The dissociation (k(off) similar to 1.5 s(-1)) and association (k(on) similar to 5.1 x 10(9) M(-1)s(-1)) rate constants for Sox2 are reduced 4-fold and increased 5-fold, respectively, in the presence of Oct1. k(off) (similar to 3.5 s(-1)) for Oct1 is unaffected by Sox2, whereas k(on) (similar to 1.3 x 10(9) M(-1)s(-1)) is increased similar to 13-fold. The direct intermolecular translocation rate (k(inter) similar to 1.8 x 10(4)M(-1)s(-1)) for the POUS domain of Oct1 is reduced 2-fold by Sox2, whereas that for the POU homeodomain (POUHD) of Oct1 (k(inter) similar to 1.7 x 10(4) M(-1)s(-1)) remains unaltered, consistent with the absence of contacts between Sox2 and POUHD. The data suggest a model for the sequence of binding events involved in synergistic gene regulation by Sox2 and Oct1.
C1 [Takayama, Yuki; Clore, G. Marius] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
RP Clore, GM (reprint author), NIDDK, Chem Phys Lab, NIH, Bldg 5, Bethesda, MD 20892 USA.
EM mariusc@intra.niddk.nih.gov
RI Clore, G. Marius/A-3511-2008
OI Clore, G. Marius/0000-0003-3809-1027
FU NIDDK, National Institutes of Health; AIDS Targeted Antiviral Program of
the Office of the Director of the National Institutes of Health; Japan
Society for the Promotion of Science
FX This work was supported, in whole or in part, by the intramural program
of NIDDK, National Institutes of Health and by the AIDS Targeted
Antiviral Program of the Office of the Director of the National
Institutes of Health (to G. M. C.).; Recipient of a Japan Society for
the Promotion of Science Research Fellowship for Japanese Biomedical and
Behavioral Researchers at the National Institutes of Health.
NR 36
TC 7
Z9 7
U1 1
U2 3
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD AUG 3
PY 2012
VL 287
IS 32
BP 26962
EP 26970
DI 10.1074/jbc.M112.382960
PG 9
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 986ZK
UT WOS:000307386000044
PM 22718759
ER
PT J
AU Venditti, V
Clore, GM
AF Venditti, Vincenzo
Clore, G. Marius
TI Conformational Selection and Substrate Binding Regulate the
Monomer/Dimer Equilibrium of the C-terminal domain of Escherichia coli
Enzyme I
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID SUGAR PHOSPHOTRANSFERASE SYSTEM; RESIDUAL DIPOLAR COUPLINGS;
SALMONELLA-TYPHIMURIUM; NMR STRUCTURES; CHEMICAL-EXCHANGE; PROTEIN
COMPLEXES; CRYSTAL-STRUCTURE; TIME-SCALE; PHOSPHOENOLPYRUVATE; TRANSPORT
AB The bacterial phosphotransferase system (PTS) is a signal transduction pathway that couples phosphoryl transfer to active sugar transport across the cell membrane. The PTS is initiated by the binding of phosphoenolpyruvate (PEP) to the C-terminal domain (EIC) of enzyme I (EI), a highly conserved protein that is common to all sugar branches of the PTS. EIC exists in a dynamic monomer/dimer equilibrium that is modulated by ligand binding and is thought to regulate the overall PTS. Isolation of EIC has proven challenging, and conformational dynamics within the EIC domain during the catalytic cycle are still largely unknown. Here, we present a robust protocol for expression and purification of recombinant EIC from Escherichia coli and show that isolated EIC is capable of hydrolyzing PEP. NMR analysis and residual dipolar coupling measurements indicate that the isolated EIC domain in solution adopts a stable tertiary fold and quaternary structure that is consistent with previously reported crystallographic data. NMR relaxation dispersion measurements indicate that residues around the PEP binding site and in the beta 3 alpha 3 turn (residues 333-366), which is located at the dimer interface, undergo a rapid transition on the sub-millisecond time scale (with an exchange rate constant of similar to 1500 s(-1)) between major open (similar to 97%) and minor closed (similar to 3%) conformations. Upon PEP binding, the beta 3 alpha 3 turn is effectively locked in the closed state by the formation of salt bridges between the phosphate group of PEP and the side chains of Lys(340) and Arg(358), thereby stabilizing the dimer.
C1 [Venditti, Vincenzo; Clore, G. Marius] NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
RP Clore, GM (reprint author), NIDDKD, Chem Phys Lab, NIH, Bldg 5, Bethesda, MD 20892 USA.
EM mariusc@mail.nih.gov
RI Venditti, Vincenzo/A-9411-2013; Clore, G. Marius/A-3511-2008
OI Clore, G. Marius/0000-0003-3809-1027
FU National Institutes of Health, NIDDK; Intramural AIDS Targeted Antiviral
Program of the Office of the Director of the National Institutes of
Health
FX This work was supported by the Intramural Program of the National
Institutes of Health, NIDDK, and the Intramural AIDS Targeted Antiviral
Program of the Office of the Director of the National Institutes of
Health (to G.M.C.).
NR 53
TC 12
Z9 12
U1 1
U2 12
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD AUG 3
PY 2012
VL 287
IS 32
BP 26989
EP 26998
DI 10.1074/jbc.M112.382291
PG 10
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 986ZK
UT WOS:000307386000046
PM 22722931
ER
PT J
AU Zhang, YL
Muthana, SM
Barchi, JJ
Gildersleeve, JC
AF Zhang, Yalong
Muthana, Saddam M.
Barchi, Joseph J., Jr.
Gildersleeve, Jeffrey C.
TI Divergent Behavior of Glycosylated Threonine and Serine Derivatives in
Solid Phase Peptide Synthesis
SO ORGANIC LETTERS
LA English
DT Article
ID CHEMICAL-SYNTHESIS; GLYCOPEPTIDE; GLYCOPROTEINS; ANTIGENS; TOOLS
AB Solid phase peptide coupling of glycosylated threonlne derivatives was systematically evaluated. In contrast to glycosylated serine derivatives which are highly prone to epimerization, glycosylated threonine derivatives produce only negligible amounts of epimerization. Under forcing conditions, glycosylated threonine analogs undergo beta-elimination, rather than epimerization. Mechanistic studies and molecular modeling were used to understand the origin of the differences in reactivity.
C1 [Zhang, Yalong; Muthana, Saddam M.; Barchi, Joseph J., Jr.; Gildersleeve, Jeffrey C.] NCI, Biol Chem Lab, Frederick, MD 21702 USA.
RP Gildersleeve, JC (reprint author), NCI, Biol Chem Lab, 376 Boyles St,Bldg 376, Frederick, MD 21702 USA.
EM gildersj@mail.nih.gov
RI Gildersleeve, Jeffrey/N-3392-2014; Barchi Jr., Joseph/N-3784-2014
FU NIH, NCI
FX This research was supported by the Intramural Research Program of the
NIH, NCI. We gratefully acknowledge James A. Kelley (NIH/NCI) for
obtaining mass spectrometry data for all the compounds.
NR 21
TC 6
Z9 6
U1 2
U2 22
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1523-7060
J9 ORG LETT
JI Org. Lett.
PD AUG 3
PY 2012
VL 14
IS 15
BP 3958
EP 3961
DI 10.1021/ol301723e
PG 4
WC Chemistry, Organic
SC Chemistry
GA 982KI
UT WOS:000307041600038
PM 22817697
ER
PT J
AU Zhou, BR
Feng, HQ
Ghirlando, R
Kato, H
Gruschus, J
Bai, YW
AF Zhou, Bing-Rui
Feng, Hanqiao
Ghirlando, Rodolfo
Kato, Hidenori
Gruschus, James
Bai, Yawen
TI Histone H4 K16Q Mutation, an Acetylation Mimic, Causes Structural
Disorder of Its N-Terminal Basic Patch in the Nucleosome
SO JOURNAL OF MOLECULAR BIOLOGY
LA English
DT Article
DE nucleosome; NMR; histone; chromatin remodeling
ID CHROMATIN FIBER; SEDIMENTATION-VELOCITY; CORE PARTICLE; NMR; MOBILITY;
TAILS; ULTRACENTRIFUGATION; ORGANIZATION; ARCHITECTURE; RESOLUTION
AB Histone tails and their posttranslational modifications play important roles in regulating the structure and dynamics of chromatin. For histone H4, the basic patch K16R17H18R19 in the N-terminal tail modulates chromatin compaction and nucleosome sliding catalyzed by ATP-dependent ISWI chromatin remodeling enzymes while acetylation of H4 K16 affects both functions. The structural basis for the effects of this acetylation is unknown. Here, we investigated the conformation of histone tails in the nucleosome by solution NMR. We found that backbone amides of the N-terminal tails of histones H2A, H2B, and H3 are largely observable due to their conformational disorder. However, only residues 1-15 in H4 can be detected, indicating that residues 16-22 in the tails of both H4 histones fold onto the nucleosome core. Surprisingly, we found that K16Q mutation in H4, a mimic of K16 acetylation, leads to a structural disorder of the basic patch. Thus, our study suggests that the folded structure of the H4 basic patch in the nucleosome is important for chromatin compaction and nucleosome remodeling by ISWI enzymes while K16 acetylation affects both functions by causing structural disorder of the basic patch K16R17H18R19. Published by Elsevier Ltd.
C1 [Zhou, Bing-Rui; Feng, Hanqiao; Kato, Hidenori; Bai, Yawen] NCI, Biochem & Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Ghirlando, Rodolfo] NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
[Gruschus, James] NHLBI, Lab Mol Biophys, NIH, Bethesda, MD 20892 USA.
RP Bai, YW (reprint author), NCI, Biochem & Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM yawen@helix.nih.gov
FU National Institutes of Health: National Cancer Institute; National
Institute of Diabetes and Digestive and Kidney Diseases; National Heart,
Lung, and Blood Institute
FX We thank Drs. Carl Wu and Tim Richmond for providing the plasmids of
histones and the 601 DNA, respectively. This work was supported by the
intramural research programs of National Institutes of Health: National
Cancer Institute (B.Z., H.F., H.K., and Y.B.), National Institute of
Diabetes and Digestive and Kidney Diseases (R.G.), and National Heart,
Lung, and Blood Institute (J.G.).
NR 35
TC 15
Z9 16
U1 0
U2 7
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0022-2836
J9 J MOL BIOL
JI J. Mol. Biol.
PD AUG 3
PY 2012
VL 421
IS 1
BP 30
EP 37
DI 10.1016/j.jmb.2012.04.032
PG 8
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 978TD
UT WOS:000306767800004
PM 22575889
ER
PT J
AU Oeemig, JS
Zhou, DW
Kajander, T
Wlodawer, A
Iwai, H
AF Oeemig, Jesper S.
Zhou, Dongwen
Kajander, Tommi
Wlodawer, Alexander
Iwai, Hideo
TI NMR and Crystal Structures of the Pyrococcus horikoshii RadA Intein
Guide a Strategy for Engineering a Highly Efficient and Promiscuous
Intein
SO JOURNAL OF MOLECULAR BIOLOGY
LA English
DT Article
DE protein engineering; protein splicing; extein; trans-splicing; segmental
labeling
ID PROTEIN SPLICING MECHANISM; RAY-DIFFRACTION DATA; SPLIT INTEIN; DNAE
INTEIN; MULTIDOMAIN PROTEIN; NOSTOC-PUNCTIFORME; IN-VIVO; SOFTWARE;
LIGATION; CLEAVAGE
AB In protein splicing, an intervening protein sequence (intein) in the host protein excises itself out and ligates two split host protein sequences (exteins) to produce a mature host protein. Inteins require the involvement for the splicing of the first residue of the extein that follows the intein (which is Cys, Ser, or Thr). Other extein residues near the splicing junctions could modulate splicing efficiency even when they are not directly involved in catalysis. Mutual interdependence between this molecular parasite (intein) and its host protein (exteins) is not beneficial for intein spread but could be advantageous for intein survival during evolution. Elucidating extein intein dependency has increasingly become important since inteins are recognized as useful biotechnological tools for protein ligation. We determined the structures of one of inteins with high splicing efficiency, the RadA intein from Pyrococcus horikoshii (PhoRadA). The solution NMR structure and the crystal structures elucidated the structural basis for its high efficiency and directed our efforts of engineering that led to rational design of a functional minimized RadA intein. The crystal structure of the minimized RadA intein also revealed the precise interactions between N-extein and the intein. We systematically analyzed the effects at the -1 position of N-extein and were able to significantly improve the splicing efficiency of a less robust splicing variant by eliminating the unfavorable extein intein interactions observed in the structure. This work provides an example of how unveiling structure-function relationships of inteins offer a promising way of improving their properties as better tools for protein engineering. (C) 2012 Elsevier Ltd. All rights reserved.
C1 [Oeemig, Jesper S.; Kajander, Tommi; Iwai, Hideo] Univ Helsinki, Inst Biotechnol, Res Program Struct Biol & Biophys, FIN-00014 Helsinki, Finland.
[Zhou, Dongwen; Wlodawer, Alexander] NCI, Macromol Crystallog Lab, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
RP Iwai, H (reprint author), Univ Helsinki, Inst Biotechnol, Res Program Struct Biol & Biophys, POB 65, FIN-00014 Helsinki, Finland.
EM hideo.iwai@helsinki.fi
RI Iwai, Hideo/A-6416-2009;
OI Iwai, Hideo/0000-0001-7376-5264; Kajander, Tommi/0000-0002-5094-227X
FU National Graduate School in Informational and Structural Biology;
national Grid Initiatives of Belgium, Italy, Germany, the Netherlands;
Latin America Grid infrastructure via the Gisela project; Academy of
Finland [1131413, 137995]; Biocenter Finland; National Institutes of
Health, National Cancer Institute, Center for Cancer Research; [261572]
FX We thank C. Albert and S. Ferkau for technical help in the protein and
plasmid preparations. J.S.O. acknowledges the National Graduate School
in Informational and Structural Biology for financial support. The WeNMR
project [European FP7 e-Infrastructure grant double dagger, contract no.
261572; supported by the national Grid Initiatives of Belgium, Italy,
Germany, the Netherlands (via the Dutch BiG Grid project), Portugal, UK,
South Africa, Taiwan, and the Latin America Grid infrastructure via the
Gisela project] is acknowledged for the use of web portals, computing,
and storage facilities. This work was supported in part by the Academy
of Finland (1131413 and 137995) and Biocenter Finland (for H.I., the
crystallization, and NMR facilities at the Institute of Biotechnology)
and in part by the Intramural Research Program of the National
Institutes of Health, National Cancer Institute, Center for Cancer
Research.
NR 57
TC 22
Z9 22
U1 0
U2 7
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0022-2836
J9 J MOL BIOL
JI J. Mol. Biol.
PD AUG 3
PY 2012
VL 421
IS 1
BP 85
EP 99
DI 10.1016/j.jmb.2012.04.029
PG 15
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 978TD
UT WOS:000306767800008
PM 22560994
ER
PT J
AU Pangilinan, F
Molloy, AM
Mills, JL
Troendle, JF
Parle-McDermott, A
Signore, C
O'Leary, VB
Chines, P
Seay, JM
Geiler-Samerotte, K
Mitchell, A
VanderMeer, JE
Krebs, KM
Sanchez, A
Cornman-Homonoff, J
Stone, N
Conley, M
Kirke, PN
Shane, B
Scott, JM
Brody, LC
AF Pangilinan, Faith
Molloy, Anne M.
Mills, James L.
Troendle, James F.
Parle-McDermott, Anne
Signore, Caroline
O'Leary, Valerie B.
Chines, Peter
Seay, Jessica M.
Geiler-Samerotte, Kerry
Mitchell, Adam
VanderMeer, Julia E.
Krebs, Kristine M.
Sanchez, Angelica
Cornman-Homonoff, Joshua
Stone, Nicole
Conley, Mary
Kirke, Peadar N.
Shane, Barry
Scott, John M.
Brody, Lawrence C.
TI Evaluation of common genetic variants in 82 candidate genes as risk
factors for neural tube defects
SO BMC MEDICAL GENETICS
LA English
DT Article
DE Neural tube defects; Spina bifida; Folic acid; One-carbon metabolism;
Candidate gene
ID FOLATE-RELATED GENES; DIHYDROFOLATE-REDUCTASE DHFR; MATERNAL
VITAMIN-B-12 STATUS; ONE-CARBON METABOLISM; SPINA-BIFIDA; HUMAN T;
METHYLENETETRAHYDROFOLATE REDUCTASE; IRISH POPULATION; FOLIC-ACID;
5,10-METHYLENETETRAHYDROFOLATE REDUCTASE
AB Background: Neural tube defects (NTDs) are common birth defects (similar to 1 in 1000 pregnancies in the US and Europe) that have complex origins, including environmental and genetic factors. A low level of maternal folate is one well-established risk factor, with maternal periconceptional folic acid supplementation reducing the occurrence of NTD pregnancies by 50-70%. Gene variants in the folate metabolic pathway (e.g., MTHFR rs1801133 (677 C > T) and MTHFD1 rs2236225 (R653Q)) have been found to increase NTD risk. We hypothesized that variants in additional folate/B12 pathway genes contribute to NTD risk.
Methods: A tagSNP approach was used to screen common variation in 82 candidate genes selected from the folate/B12 pathway and NTD mouse models. We initially genotyped polymorphisms in 320 Irish triads (NTD cases and their parents), including 301 cases and 341 Irish controls to perform case-control and family based association tests. Significantly associated polymorphisms were genotyped in a secondary set of 250 families that included 229 cases and 658 controls. The combined results for 1441 SNPs were used in a joint analysis to test for case and maternal effects.
Results: Nearly 70 SNPs in 30 genes were found to be associated with NTDs at the p < 0.01 level. The ten strongest association signals (p-value range: 0.0003-0.0023) were found in nine genes (MFTC, CDKN2A, ADA, PEMT, CUBN, GART, DNMT3A, MTHFD1 and T (Brachyury)) and included the known NTD risk factor MTHFD1 R653Q (rs2236225). The single strongest signal was observed in a new candidate, MFTC rs17803441 (OR = 1.61 [1.23-2.08], p = 0.0003 for the minor allele). Though nominally significant, these associations did not remain significant after correction for multiple hypothesis testing.
Conclusions: To our knowledge, with respect to sample size and scope of evaluation of candidate polymorphisms, this is the largest NTD genetic association study reported to date. The scale of the study and the stringency of correction are likely to have contributed to real associations failing to survive correction. We have produced a ranked list of variants with the strongest association signals. Variants in the highest rank of associations are likely to include true associations and should be high priority candidates for further study of NTD risk.
C1 [Pangilinan, Faith; Seay, Jessica M.; Geiler-Samerotte, Kerry; Mitchell, Adam; VanderMeer, Julia E.; Krebs, Kristine M.; Sanchez, Angelica; Cornman-Homonoff, Joshua; Stone, Nicole; Brody, Lawrence C.] NHGRI, Mol Pathogenesis Sect, Genome Technol Branch, NIH, Bethesda, MD 20892 USA.
[Molloy, Anne M.] Trinity Coll Dublin, Dept Clin Med, Dublin, Ireland.
[Mills, James L.; Conley, Mary] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, NIH, Dept Hlth & Human Serv, Bethesda, MD USA.
[Troendle, James F.] NHLBI, Dept Hlth & Human Serv, Off Biostat Res, NIH, Bethesda, MD 20892 USA.
[Parle-McDermott, Anne] Dublin City Univ, Sch Biotechnol, Dublin 9, Ireland.
[Signore, Caroline] NICHHD, Dept Hlth & Human Serv, Pregnancy & Perinatol Branch, NIH, Bethesda, MD 20892 USA.
[O'Leary, Valerie B.] Dublin City Univ, Int Ctr Neurotherapeut, Dublin 9, Ireland.
[Chines, Peter] NHGRI, Dept Hlth & Human Serv, Mol Genet Sect, Genome Technol Branch,NIH, Bethesda, MD 20892 USA.
[Kirke, Peadar N.] Hlth Res Board, Child Hlth Epidemiol Unit, Dublin, Ireland.
[Shane, Barry] Univ Calif Berkeley, Dept Nutr Sci & Toxicol, Berkeley, CA 94720 USA.
[Scott, John M.] Trinity Coll Dublin, Sch Biochem & Immunol, Dublin, Ireland.
RP Brody, LC (reprint author), NHGRI, Mol Pathogenesis Sect, Genome Technol Branch, NIH, Bethesda, MD 20892 USA.
EM lbrody@mail.nih.gov
OI Molloy, Anne/0000-0002-1688-9049; O'Leary, Valerie/0000-0003-1171-9830
FU National Institutes of Health, Eunice Kennedy Shriver National Institute
of Child Health and Human Development; National Human Genome Research
Institute
FX These studies would not be possible without the participation of the
affected families, and their recruitment by the Irish Association of
Spina Bifida and Hydrocephalus and the Irish Public Health Nurses in
Ireland. This study was supported by the Intramural Research Programs of
the National Institutes of Health, Eunice Kennedy Shriver National
Institute of Child Health and Human Development, and the National Human
Genome Research Institute.
NR 59
TC 35
Z9 37
U1 0
U2 17
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2350
J9 BMC MED GENET
JI BMC Med. Genet.
PD AUG 2
PY 2012
VL 13
AR 62
DI 10.1186/1471-2350-13-62
PG 19
WC Genetics & Heredity
SC Genetics & Heredity
GA 011PN
UT WOS:000309177400001
PM 22856873
ER
PT J
AU Jacobs, JH
Archer, BN
Baker, MG
Cowling, BJ
Heffernan, RT
Mercer, G
Uez, O
Hanshaoworakul, W
Viboud, C
Schwartz, J
Tchetgen, ET
Lipsitch, M
AF Jacobs, Jessica Hartman
Archer, Brett Nicholas
Baker, Michael G.
Cowling, Benjamin J.
Heffernan, Richard T.
Mercer, Geoff
Uez, Osvaldo
Hanshaoworakul, Wanna
Viboud, Cecile
Schwartz, Joel
Tchetgen, Eric Tchetgen
Lipsitch, Marc
TI Searching for Sharp Drops in the Incidence of Pandemic A/H1N1 Influenza
by Single Year of Age
SO PLOS ONE
LA English
DT Article
ID ORIGINAL ANTIGENIC SIN; A H1N1 VIRUS; PREEXISTING IMMUNITY; ANTIBODY;
INFECTION; RESPONSES; HUMANS
AB Background: During the 2009 H1N1 pandemic (pH1N1), morbidity and mortality sparing was observed among the elderly population; it was hypothesized that this age group benefited from immunity to pH1N1 due to cross-reactive antibodies generated from prior infection with antigenically similar influenza viruses. Evidence from serologic studies and genetic similarities between pH1N1 and historical influenza viruses suggest that the incidence of pH1N1 cases should drop markedly in age cohorts born prior to the disappearance of H1N1 in 1957, namely those at least 52-53 years old in 2009, but the precise range of ages affected has not been delineated.
Methods and Findings: To test for any age-associated discontinuities in pH1N1 incidence, we aggregated laboratory-confirmed pH1N1 case data from 8 jurisdictions in 7 countries, stratified by single year of age, sex (when available), and hospitalization status. Using single year of age population denominators, we generated smoothed curves of the weighted risk ratio of pH1N1 incidence, and looked for sharp drops at varying age bandwidths, defined as a significantly negative second derivative. Analyses stratified by hospitalization status and sex were used to test alternative explanations for observed discontinuities. We found that the risk of laboratory-confirmed infection with pH1N1 declines with age, but that there was a statistically significant leveling off or increase in risk from about 45 to 50 years of age, after which a sharp drop in risk occurs until the late fifties. This trend was more pronounced in hospitalized cases and in women and was independent of the choice in smoothing parameters. The age range at which the decline in risk accelerates corresponds to the cohort born between 1951-1959 (hospitalized) and 1953-1960 (not hospitalized).
Conclusions: The reduced incidence of pH1N1 disease in older individuals shows a detailed age-specific pattern consistent with protection conferred by exposure to influenza A/H1N1 viruses circulating before 1957.
C1 [Jacobs, Jessica Hartman; Schwartz, Joel; Tchetgen, Eric Tchetgen; Lipsitch, Marc] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Archer, Brett Nicholas] Natl Inst Communicable Dis, Natl Hlth Lab Serv, Johannesburg, South Africa.
[Baker, Michael G.] Univ Otago, Dept Publ Hlth, Wellington, New Zealand.
[Cowling, Benjamin J.] Univ Hong Kong, Sch Publ Hlth, Hong Kong, Hong Kong, Peoples R China.
[Heffernan, Richard T.] Wisconsin Dept Hlth Serv, Div Publ Hlth, Madison, WI USA.
[Mercer, Geoff] Australian Natl Univ, Natl Ctr Epidemiol & Populat Hlth, Canberra, ACT, Australia.
[Uez, Osvaldo] Minist Publ Hlth, Natl Inst Epidemiol, ANLIS, Buenos Aires, DF, Argentina.
[Hanshaoworakul, Wanna] Minist Publ Hlth, Dept Dis Control, Tiwanond, Nonthaburi, Thailand.
[Viboud, Cecile] NIH, Div Int Epidemiol & Populat Studies, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Schwartz, Joel] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA.
[Tchetgen, Eric Tchetgen] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
[Lipsitch, Marc] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA.
RP Jacobs, JH (reprint author), Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
EM jhartman44@gmail.com
RI Cowling, Benjamin/C-4263-2009;
OI Cowling, Benjamin/0000-0002-6297-7154; Lipsitch,
Marc/0000-0003-1504-9213
FU National Institute Of General Medical Sciences [U54GM088558]; MedImmune
Inc.; Roche
FX The project described was supported by the National Institute Of General
Medical Sciences [Award Number U54GM088558], http://www.nigms.nih.gov/.
The content is solely the responsibility of the authors and does not
necessarily represent the official views of the National Institute Of
General Medical Sciences or the National Institutes of Health. The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.; BJC has received
research funding from MedImmune Inc. and consults for Crucell MV. ML
declares consulting income/honoraria from Pfizer, Novartis,
Avian/Pandemic Flu Registry (Outcome Sciences, supported by Roche), and
AIR Worldwide. The following co-authors are editors: Benjamin J Cowling
and Cecile Viboud. This does not alter the authors` adherence to all the
PLoS ONE policies on sharing data and materials.
NR 40
TC 11
Z9 11
U1 0
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 2
PY 2012
VL 7
IS 8
AR e42328
DI 10.1371/journal.pone.0042328
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 984JA
UT WOS:000307184700044
PM 22876316
ER
PT J
AU Lucas, G
Lluis-Ganella, C
Subirana, I
Musameh, MD
Gonzalez, JR
Nelson, CP
Senti, M
Schwartz, SM
Siscovick, D
O'Donnell, CJ
Melander, O
Salomaa, V
Purcell, S
Altshuler, D
Samani, NJ
Kathiresan, S
Elosua, R
AF Lucas, Gavin
Lluis-Ganella, Carla
Subirana, Isaac
Musameh, Muntaser D.
Ramon Gonzalez, Juan
Nelson, Christopher P.
Senti, Mariano
Schwartz, Stephen M.
Siscovick, David
O'Donnell, Christopher J.
Melander, Olle
Salomaa, Veikko
Purcell, Shaun
Altshuler, David
Samani, Nilesh J.
Kathiresan, Sekar
Elosua, Roberto
CA Myocardial Infarction Genetics Con
Wellcome Trust Case Control Consor
TI Hypothesis-Based Analysis of Gene-Gene Interactions and Risk of
Myocardial Infarction
SO PLOS ONE
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; CORONARY-ARTERY-DISEASE; COMPLEX DISEASES;
HEART-DISEASE; EPISTASIS; LOCI; POLYMORPHISMS; HERITABILITY;
CHOLESTEROL; STRATEGIES
AB The genetic loci that have been found by genome-wide association studies to modulate risk of coronary heart disease explain only a fraction of its total variance, and gene-gene interactions have been proposed as a potential source of the remaining heritability. Given the potentially large testing burden, we sought to enrich our search space with real interactions by analyzing variants that may be more likely to interact on the basis of two distinct hypotheses: a biological hypothesis, under which MI risk is modulated by interactions between variants that are known to be relevant for its risk factors; and a statistical hypothesis, under which interacting variants individually show weak marginal association with MI. In a discovery sample of 2,967 cases of early-onset myocardial infarction (MI) and 3,075 controls from the MIGen study, we performed pair-wise SNP interaction testing using a logistic regression framework. Despite having reasonable power to detect interaction effects of plausible magnitudes, we observed no statistically significant evidence of interaction under these hypotheses, and no clear consistency between the top results in our discovery sample and those in a large validation sample of 1,766 cases of coronary heart disease and 2,938 controls from the Wellcome Trust Case-Control Consortium. Our results do not support the existence of strong interaction effects as a common risk factor for MI. Within the scope of the hypotheses we have explored, this study places a modest upper limit on the magnitude that epistatic risk effects are likely to have at the population level (odds ratio for MI risk 1.3-2.0, depending on allele frequency and interaction model).
C1 [Lucas, Gavin; Lluis-Ganella, Carla; Subirana, Isaac; Senti, Mariano; Elosua, Roberto] IMIM, Barcelona, Spain.
[Lluis-Ganella, Carla; Ramon Gonzalez, Juan; Elosua, Roberto] Epidemiol & Publ Hlth Network CIBERESP, Barcelona, Spain.
[Musameh, Muntaser D.; Nelson, Christopher P.; Samani, Nilesh J.] Univ Leicester, Dept Cardiovasc Sci, Leicester, Leics, England.
[Musameh, Muntaser D.; Nelson, Christopher P.; Samani, Nilesh J.] Glenfield Gen Hosp, Leicester NIHR Biomed Res Unit Cardiovasc Dis, Leicester LE3 9QP, Leics, England.
[Ramon Gonzalez, Juan] Ctr Res Environm Epidemiol CREAL, Barcelona, Spain.
[Ramon Gonzalez, Juan] IMIM Hosp Mar Res Inst, Barcelona, Spain.
[Senti, Mariano] Pompeu Fabra Univ, Barcelona, Spain.
[Schwartz, Stephen M.; Siscovick, David] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA.
[Schwartz, Stephen M.; Siscovick, David] Univ Washington, Dept Epidemiol, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA.
[O'Donnell, Christopher J.] NHLBI, Framingham, MA USA.
[O'Donnell, Christopher J.] Framingham Heart Dis Epidemiol Study, Framingham, MA USA.
[O'Donnell, Christopher J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA.
[Melander, Olle] Lund Univ, Malmo Univ Hosp, Dept Clin Sci Hypertens & Cardiovasc Dis, Malmo, Sweden.
[Salomaa, Veikko] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland.
[Purcell, Shaun] Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA.
[Purcell, Shaun] Broad Inst, Stanley Ctr Psychiat Res, Cambridge, MA USA.
[Altshuler, David; Kathiresan, Sekar] Broad Inst MIT & Harvard, Cambridge, MA USA.
[Altshuler, David] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA.
[Altshuler, David] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA.
[Kathiresan, Sekar] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Kathiresan, Sekar] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.
[Kathiresan, Sekar] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
RP Lucas, G (reprint author), IMIM, Barcelona, Spain.
EM glucas@imim.es
RI Lluis-Ganella, Carla/G-5998-2012; Altshuler, David/A-4476-2009; Senti,
M/D-4309-2014; Ramos , Rafel/D-9627-2016;
OI Hattersley, Andrew/0000-0001-5620-473X; Lluis-Ganella,
Carla/0000-0001-7609-5497; Altshuler, David/0000-0002-7250-4107; Ramos ,
Rafel/0000-0001-8146-5288; Ramos , Rafel/0000-0001-7970-5537; ELOSUA,
ROBERTO/0000-0001-8235-0095; Piazza, Alberto/0000-0002-2355-4183; Senti,
Mariano/0000-0002-6983-3831; Schwartz, Stephen/0000-0001-7499-8502;
Marrugat, Jaume/0000-0003-3320-554X; Ouwehand,
Willem/0000-0002-7744-1790
FU National Institutes of Health, USA [R01 HL087676]; Wellcome Trust
[085475]; ACC1O [RD08-1-0024]; European Regional Development Fund
(ERDF-FEDER); Spanish Ministry of Science and Innovation through Carlos
III Health Institute (CIBER Epidemiologia y Salud Publica, Red HERACLES
and GENOMet network) [RD06/0009, PI061254, PI09/90506, MTM2010-09526-E];
Catalan Research and Technology Innovation Interdepartmental Commission
[SGR 1195]; Fundacio La Marato de TV3 [1081810, 080431]; Academy of
Finland [129494, 139635]; Juan de la Cierva Program, Ministerio de
Educacion [JCI-2009-04684]
FX The Myocardial Infarction Genetics Consortium (MIGen) was funded by
grant R01 HL087676 from the National Institutes of Health, USA. The
Wellcome Trust Case-Control Consortium 2 was funded by the Wellcome
Trust under award 085475. This work was supported by a grant from ACC1O
(RD08-1-0024), the European Regional Development Fund (ERDF-FEDER), the
Spanish Ministry of Science and Innovation through the Carlos III Health
Institute (CIBER Epidemiologia y Salud Publica, Red HERACLES RD06/0009,
PI061254, PI09/90506 and the GENOMet network, MTM2010-09526-E), the
Catalan Research and Technology Innovation Interdepartmental Commission
(SGR 1195) and Fundacio La Marato de TV3 (1081810; 080431). VS was
supported by the Academy of Finland (grants # 129494 and 139635). GL was
funded by the Juan de la Cierva Program, Ministerio de Educacion
(JCI-2009-04684). The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 34
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U1 0
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 2
PY 2012
VL 7
IS 8
AR e41730
DI 10.1371/journal.pone.0041730
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 984JA
UT WOS:000307184700020
PM 22876292
ER
PT J
AU Wang, JB
Fan, JH
Liang, H
Li, J
Xiao, HJ
Wei, WQ
Dawsey, SM
Qiao, YL
Boffetta, P
AF Wang, Jian-Bing
Fan, Jin-Hu
Liang, Hao
Li, Jing
Xiao, Hui-Juan
Wei, Wen-Qiang
Dawsey, Sanford M.
Qiao, You-Lin
Boffetta, Paolo
TI Attributable Causes of Esophageal Cancer Incidence and Mortality in
China
SO PLOS ONE
LA English
DT Article
ID RISK-FACTORS; ALCOHOL-DRINKING; GASTRIC CANCERS; CIGARETTE-SMOKING;
BRITISH DOCTORS; LIFE-STYLE; TOOTH LOSS; DISEASE; COHORT; FRUIT
AB Background: To estimate the contribution of tobacco smoking, alcohol drinking, low vegetable intake and low fruit intake to esophageal cancer mortality and incidence in China.
Methodology/Principal Findings: We calculated the proportion of esophageal cancer attributable to four known modifiable risk factors [population attributable fraction (PAF)]. Exposure data was taken from meta-analyses and large-scale national surveys of representative samples of the Chinese population. Data on relative risks were also from meta-analyses and large-scale prospective studies. Esophageal cancer mortality and incidence came from the 3rd national death cause survey and population-based cancer registries in China. We estimated that 87,065 esophageal cancer deaths (men 67,686; women: 19,379) and 108,206 cases (men: 83,968, women: 24,238) were attributable to tobacco smoking, alcohol drinking, low vegetable intake and low fruit intake in China in 2005. About 17.9% of esophageal cancer deaths among men and 1.9% among women were attributable to tobacco smoking. About 15.2% of esophageal cancer deaths in men and 1.3% in women were caused by alcohol drinking. Low vegetable intake was responsible for 4.3% esophageal cancer deaths in men and 4.1% in women. The fraction of esophageal cancer deaths attributable to low fruit intake was 27.1% in men and 28.0% in women. Overall, 46% of esophageal cancers (51% in men and 33% in women) were attributable to these four modifiable risk factors.
Conclusions/Significance: Tobacco smoking, alcohol drinking, low vegetable intake and low fruit intake were responsible for 46% of esophageal cancer mortality and incidence in China in 2005. These findings provide useful data for developing guidelines for esophageal cancer prevention and control in China.
C1 [Wang, Jian-Bing; Fan, Jin-Hu; Liang, Hao; Li, Jing; Wei, Wen-Qiang; Qiao, You-Lin] Chinese Acad Med Sci, Dept Canc Epidemiol, Peking Union Med Coll, Canc Inst Hosp, Beijing 100730, Peoples R China.
[Wang, Jian-Bing; Dawsey, Sanford M.] NCI, Div Canc Epidemiol & Genet, Nutr Epidemiol Branch, Bethesda, MD 20892 USA.
[Xiao, Hui-Juan] Tianjin Third Cent Hosp, Dept Nutr, Tianjin, Peoples R China.
[Boffetta, Paolo] Mt Sinai Sch Med, Tisch Canc Inst, New York, NY USA.
[Boffetta, Paolo] Int Prevent Res Inst, Lyon, France.
RP Wang, JB (reprint author), Chinese Acad Med Sci, Dept Canc Epidemiol, Peking Union Med Coll, Canc Inst Hosp, Beijing 100730, Peoples R China.
EM qiaoy@cicams.ac.cn; paolo.boffetta@i-pri.org
RI Qiao, You-Lin/B-4139-2012
OI Qiao, You-Lin/0000-0001-6380-0871
FU International Agency for Research on Cancer (Lyon, France) [GEE/08/19];
National Institutes of Health, National Cancer Institute, Division of
Cancer Epidemiology and Genetics
FX This research was supported by the International Agency for Research on
Cancer (Lyon, France), Grant number: CRA No GEE/08/19. It was also
supported in part by the Intramural Research Program of the National
Institutes of Health, National Cancer Institute, Division of Cancer
Epidemiology and Genetics. The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 40
TC 24
Z9 29
U1 0
U2 8
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 2
PY 2012
VL 7
IS 8
AR e42281
DI 10.1371/journal.pone.0042281
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 984JA
UT WOS:000307184700040
PM 22876312
ER
PT J
AU Beachy, SH
Onozawa, M
Chung, YJ
Slape, C
Bilke, S
Francis, P
Pineda, M
Walker, RL
Meltzer, P
Aplan, PD
AF Beachy, Sarah H.
Onozawa, Masahiro
Chung, Yang Jo
Slape, Chris
Bilke, Sven
Francis, Princy
Pineda, Marbin
Walker, Robert L.
Meltzer, Paul
Aplan, Peter D.
TI Enforced expression of Lin28b leads to impaired T-cell development,
release of inflammatory cytokines, and peripheral T-cell lymphoma
SO BLOOD
LA English
DT Article
ID NF-KAPPA-B; HUMAN HEPATOCELLULAR-CARCINOMA; TRANSGENIC MICE;
MYELODYSPLASTIC SYNDROME; PROMOTES TRANSFORMATION; NOTCH1 MUTATIONS;
ACUTE-LEUKEMIA; CANCER; GENE; ACTIVATION
AB LIN28A and LIN28B, the mammalian homologs of lin-28, are implicated in malignant transformation in part because of their ability to promote degradation of the let-7 family of miRs. In the present study, we show that overexpression of Lin28b in vivo leads to an aggressive peripheral T-cell lymphoma (PTCL) characterized by widespread infiltration of parenchymal organs with malignant CD4(+) cells. Similar to patients with PTCL, Lin28b-transgenic mice show signs of inflammation such as eosinophilia, increased C-reactive protein, release of inflammatory cytokines, and pleural effusion. The PTCLs that develop in Lin28b mice are derived from activated T cells and show decreased let-7 expression, increased Il6 expression, activation of NF-kappa B, and infiltration of B cells, all resulting in an inflammatory microenvironment. In addition, LIN28B is overexpressed 7.5-fold in PTCL patient samples compared with activated CD4(+) cells. The results of the present study demonstrate for the first time that Lin28b can transform primary cells in vivo, identify a previously unsuspected link between Lin28b and PTCL, and provide a unique animal model for the study of PTCL biology and therapy. (Blood. 2012; 120(5): 1048-1059)
C1 [Beachy, Sarah H.; Onozawa, Masahiro; Chung, Yang Jo; Bilke, Sven; Francis, Princy; Pineda, Marbin; Walker, Robert L.; Meltzer, Paul; Aplan, Peter D.] NCI, Genet Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Slape, Chris] Monash Univ, Cent Clin Sch, Melbourne, Vic 3004, Australia.
RP Aplan, PD (reprint author), NCI, Genet Branch, Ctr Canc Res, NIH, 41 Ctr Dr, Bethesda, MD 20892 USA.
EM aplanp@mail.nih.gov
RI Slape, Christopher/H-8586-2016; Aplan, Peter/K-9064-2016
OI Slape, Christopher/0000-0002-8407-3092;
FU Intramural Research Program of the National Cancer Institute, National
Institutes of Health (Bethesda, MD)
FX This research was supported by the Intramural Research Program of the
National Cancer Institute, National Institutes of Health (Bethesda, MD).
NR 50
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U1 0
U2 4
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD AUG 2
PY 2012
VL 120
IS 5
BP 1048
EP 1059
DI 10.1182/blood-2012-01-401760
PG 12
WC Hematology
SC Hematology
GA 987VS
UT WOS:000307446500016
PM 22723554
ER
PT J
AU Huang, XG
Di Liberto, M
Jayabalan, D
Liang, J
Ely, S
Bretz, J
Shaffer, AL
Louie, T
Chen, I
Randolph, S
Hahn, WC
Staudt, LM
Niesvizky, R
Moore, MAS
Chen-Kiang, S
AF Huang, Xiangao
Di Liberto, Maurizio
Jayabalan, David
Liang, Jun
Ely, Scott
Bretz, Jamieson
Shaffer, Arthur L., III
Louie, Tracey
Chen, Isan
Randolph, Sophia
Hahn, William C.
Staudt, Louis M.
Niesvizky, Ruben
Moore, Malcolm A. S.
Chen-Kiang, Selina
TI Prolonged early G(1) arrest by selective CDK4/CDK6 inhibition sensitizes
myeloma cells to cytotoxic killing through cell cycle-coupled loss of
IRF4
SO BLOOD
LA English
DT Article
ID MULTIPLE-MYELOMA; CDK INHIBITORS; KINASE-ACTIVITY; BREAST-CANCER;
IN-VITRO; P18(INK4C); TUMORIGENESIS; EXPRESSION; DIFFERENTIATION;
DYSREGULATION
AB Dysregulation of cyclin-dependent kinase 4 (CDK4) and CDK6 by gain of function or loss of inhibition is common in human cancer, including multiple myeloma, but success in targeting CDK with broad-spectrum inhibitors has been modest. By selective and reversible inhibition of CDK4/CDK6, we have developed a strategy to both inhibit proliferation and enhance cytotoxic killing of cancer cells. We show that induction of prolonged early-G(1) arrest (pG1) by CDK4/CDK6 inhibition halts gene expression in early-G1 and prevents expression of genes programmed for other cell-cycle phases. Removal of the early-G(1) block leads to S-phase synchronization (pG1-S) but fails to completely restore scheduled gene expression. Consequently, the IRF4 protein required to protect myeloma cells from apoptosis is markedly reduced in pG1 and further in pG1-S in response to cytotoxic agents, such as the proteasome inhibitor bortezomib. The coordinated loss of IRF4 and gain of Bim sensitize myeloma tumor cells to bortezomib-induced apoptosis in pG1 in the absence of Noxa and more profoundly in pG1-S in cooperation with Noxa in vitro. Induction of pG1 and pG1-S by reversible CDK4/CDK6 inhibition further augments tumor-specific bortezomib killing in myeloma xenografts. Reversible inhibition of CDK4/CDK6 in sequential combination therapy thus represents a novel mechanism-based cancer therapy. (Blood. 2012;120(5):1095-1106)
C1 [Huang, Xiangao; Di Liberto, Maurizio; Jayabalan, David; Liang, Jun; Ely, Scott; Louie, Tracey; Chen-Kiang, Selina] Weill Cornell Med Coll, Dept Pathol & Lab Med, New York, NY 10065 USA.
[Jayabalan, David; Niesvizky, Ruben] Weill Cornell Med Coll, Dept Med, New York, NY 10065 USA.
[Bretz, Jamieson; Chen-Kiang, Selina] Weill Cornell Med Coll, Grad Program Immunol & Microbial Pathogenesis, New York, NY 10065 USA.
[Shaffer, Arthur L., III; Staudt, Louis M.] NIH, Metab Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Chen, Isan; Randolph, Sophia] Pfizer Oncol, San Diego, CA USA.
[Hahn, William C.] Dana Farber Canc Inst, Dept Med Oncol, Broad Inst Harvard & Massachusetts Inst Technol, Boston, MA 02115 USA.
[Moore, Malcolm A. S.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
RP Chen-Kiang, S (reprint author), Weill Cornell Med Coll, Dept Pathol & Lab Med, 1300 York Ave,C-338, New York, NY 10065 USA.
EM sckiang@med.cornell.edu
FU National Institutes of Health, National Cancer Institute, Center for
Cancer Research [NCI R01 120531]; Leukemia & Lymphoma Society; Starr
Cancer Consortium grant
FX This work was supported by the Intramural Research Program of the
National Institutes of Health, National Cancer Institute, Center for
Cancer Research (A.L.S. and L.M.S.; NCI R01 120531, S.C.-K.), a Leukemia
& Lymphoma Society Translational Research Program grant (S.C.-K.), and a
Starr Cancer Consortium grant (W.C.H. and S.C.-K.).
NR 47
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U1 0
U2 5
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD AUG 2
PY 2012
VL 120
IS 5
BP 1095
EP 1106
DI 10.1182/blood-2012-03-415984
PG 12
WC Hematology
SC Hematology
GA 987VS
UT WOS:000307446500021
PM 22718837
ER
PT J
AU Shen, Y
Yue, F
McCleary, DF
Ye, Z
Edsall, L
Kuan, S
Wagner, U
Dixon, J
Lee, L
Lobanenkov, VV
Ren, B
AF Shen, Yin
Yue, Feng
McCleary, David F.
Ye, Zhen
Edsall, Lee
Kuan, Samantha
Wagner, Ulrich
Dixon, Jesse
Lee, Leonard
Lobanenkov, Victor V.
Ren, Bing
TI A map of the cis-regulatory sequences in the mouse genome
SO NATURE
LA English
DT Article
ID GENE-EXPRESSION; CHROMATIN INTERACTIONS; FUNCTIONAL ELEMENTS; HUMAN
ENHANCERS; REVEALS; IDENTIFICATION; VERTEBRATE; PROMOTERS; MODENCODE;
DYNAMICS
AB The laboratory mouse is the most widely used mammalian model organism in biomedical research. The 2.6 x 10(9) bases of the mouse genome possess a high degree of conservation with the human genome(1), so a thorough annotation of the mouse genome will be of significant value to understanding the function of the human genome. So far, most of the functional sequences in the mouse genome have yet to be found, and the cis-regulatory sequences in particular are still poorly annotated. Comparative genomics has been a powerful tool for the discovery of these sequences(2), but on its own it cannot resolve their temporal and spatial functions. Recently, ChIP-Seq has been developed to identify cis-regulatory elements in the genomes of several organisms including humans, Drosophila melanogaster and Caenorhabditis elegans(3-5). Here we apply the same experimental approach to a diverse set of 19 tissues and cell types in the mouse to produce a map of nearly 300,000 murine cis-regulatory sequences. The annotated sequences add up to 11% of the mouse
[GRAPHICS]
genome, and include more than 70% of conserved non-coding sequences. We define tissue-specific enhancers and identify potential transcription factors regulating gene expression in each tissue or cell type. Finally, we show that much of the mouse genome is organized into domains of coordinately regulated enhancers and promoters. Our results provide a resource for the annotation of functional elements in the mammalian genome and for the study of mechanisms regulating tissue-specific gene expression.
C1 [Shen, Yin; Yue, Feng; McCleary, David F.; Ye, Zhen; Edsall, Lee; Kuan, Samantha; Wagner, Ulrich; Dixon, Jesse; Lee, Leonard; Ren, Bing] Ludwig Inst Canc Res, La Jolla, CA 92093 USA.
[Dixon, Jesse] Univ Calif San Diego, Sch Med, Med Scientist Training Program, La Jolla, CA 92093 USA.
[Dixon, Jesse] Univ Calif San Diego, Sch Med, Biomed Sci Grad Program, La Jolla, CA 92093 USA.
[Lobanenkov, Victor V.] NIAID, Immunogenet Lab, Twinbrook NIAID Facil 1, Rockville, MD 20852 USA.
[Ren, Bing] Univ Calif San Diego, Sch Med, Moores Canc Ctr, Dept Cellular & Mol Med,Inst Genom Med, La Jolla, CA 92093 USA.
RP Ren, B (reprint author), Ludwig Inst Canc Res, 9500 Gilman Dr, La Jolla, CA 92093 USA.
EM biren@ucsd.edu
OI Lobanenkov, Victor/0000-0001-6665-3635; Edsall, Lee
Elizabeth/0000-0002-0326-2829
FU National Human Genome Research Institute [R01HG003991]; Ludwig Institute
for Cancer Research; International Rett Syndrome Foundation; California
Institute for Regenerative Medicine
FX We thank F. Jin, Y. Luu, S. Klugman, A. Y.-J. Kim, Q.-M. Ngo, B. A.
Gomez and S. Selvaraj for consultation. The mESC line Bruce4 was a gift
from UCSD Transgenic Core. Research funding was provided by the National
Human Genome Research Institute (R01HG003991) and the Ludwig Institute
for Cancer Research to B. R. Y. S. is supported by a postdoctoral
fellowship from the International Rett Syndrome Foundation. J.D. is
supported by a pre-doctoral fellowship from the California Institute for
Regenerative Medicine.
NR 30
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U1 12
U2 89
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
J9 NATURE
JI Nature
PD AUG 2
PY 2012
VL 488
IS 7409
BP 116
EP 120
DI 10.1038/nature11243
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 981ZE
UT WOS:000307010700044
PM 22763441
ER
PT J
AU Shirota, H
Klinman, DM
AF Shirota, Hidekazu
Klinman, Dennis M.
TI Effect of CpG ODN on monocytic myeloid derived suppressor cells
SO ONCOIMMUNOLOGY
LA English
DT Editorial Material
DE myeloid-derived suppressor cells; tumor-associated macrophages; CpG ODN;
toll like receptor; immunotherapy; tumor microenvironment; myeloid
derived suppressor cells; CpG oligonucleotides; TLR9; immunotherapy;
tumor microenvironment
ID CANCER; PF-3512676; CARCINOMA; MELANOMA
AB CpG oligonucleotides stimulate via TLR9 and enhance anti-tumor immunity, an effect attributed to the activation of NK and CD8+ T cells. Our recent work demonstrates that CpG ODN also induce monocytic myeloid-derived suppressor cells to mature into M1 macrophages, further aiding tumor elimination. This provides insight into the mechanism through which CpG promote tumor regression.
C1 [Shirota, Hidekazu; Klinman, Dennis M.] NCI, Canc & Inflammat Program, Frederick, MD 21701 USA.
[Shirota, Hidekazu] SAIC Frederick Inc, Basic Sci Program, Frederick, MD USA.
RP Klinman, DM (reprint author), NCI, Canc & Inflammat Program, Frederick, MD 21701 USA.
EM klinmand@mail.nih.gov
NR 11
TC 8
Z9 8
U1 0
U2 0
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA
SN 2162-4011
J9 ONCOIMMUNOLOGY
JI OncoImmunology
PD AUG
PY 2012
VL 1
IS 5
BP 780
EP 782
DI 10.4161/onci.19731
PG 3
WC Oncology; Immunology
SC Oncology; Immunology
GA 108EL
UT WOS:000316274400033
ER
PT J
AU Brautbar, A
Pompeii, LA
Dehghan, A
Ngwa, JS
Nambi, V
Virani, SS
Rivadeneira, F
Uitterlinden, AG
Hofman, A
Witteman, JCM
Pencina, MJ
Folsom, AR
Cupples, LA
Ballantyne, CM
Boerwinkle, E
AF Brautbar, Ariel
Pompeii, Lisa A.
Dehghan, Abbas
Ngwa, Julius S.
Nambi, Vijay
Virani, Salim S.
Rivadeneira, Fernando
Uitterlinden, Andre G.
Hofman, Albert
Witteman, Jacqueline C. M.
Pencina, Michael J.
Folsom, Aaron R.
Cupples, L. Adrienne
Ballantyne, Christie M.
Boerwinkle, Eric
TI A genetic risk score based on direct associations with coronary heart
disease improves coronary heart disease risk prediction in the
Atherosclerosis Risk in Communities (ARIC), but not in the Rotterdam and
Framingham Offspring, Studies
SO ATHEROSCLEROSIS
LA English
DT Article
DE Genetics; Risk factors; Coronary disease
ID INTIMA-MEDIA THICKNESS; CARDIOVASCULAR EVENTS; MYOCARDIAL-INFARCTION;
CHROMOSOME 9P21.3; RECLASSIFICATION; VARIANTS; DESIGN; OBJECTIVES;
PLAQUE; LOCUS
AB Objective: Multiple studies have identified single-nucleotide polymorphisms (SNPs) that are associated with coronary heart disease (CHD). We examined whether SNPs selected based on predefined criteria will improve CHD risk prediction when added to traditional risk factors (TRFs).
Methods: SNPs were selected from the literature based on association with CHD, lack of association with a known CHD risk factor, and successful replication. A genetic risk score (GRS) was constructed based on these SNPs. Cox proportional hazards model was used to calculate CHD risk based on the Atherosclerosis Risk in Communities (ARIC) and Framingham CHD risk scores with and without the GRS.
Results: The GRS was associated with risk for CHD (hazard ratio [HR] = 1.10; 95% confidence interval [CI]: 1.07-1.13). Addition of the GRS to the ARIC risk score significantly improved discrimination, reclassification, and calibration beyond that afforded by TRFs alone in non-Hispanic whites in the ARIC study. The area under the receiver operating characteristic curve (AUC) increased from 0.742 to 0.749 (Delta = 0.007; 95% CI, 0.004-0.013), and the net reclassification index (NRI) was 6.3%. Although the risk estimates for CHD in the Framingham Offspring (HR = 1.12; 95% CI: 1.10-1.14) and Rotterdam (HR = 1.08; 95% CI: 1.02-1.14) Studies were significantly improved by adding the GRS to TRFs, improvements in AUC and NRI were modest.
Conclusion: Addition of a GRS based on direct associations with CHD to TRFs significantly improved discrimination and reclassification in white participants of the ARIC Study, with no significant improvement in the Rotterdam and Framingham Offspring Studies. (C) 2012 Elsevier Ireland Ltd. All rights reserved.
C1 [Brautbar, Ariel] Marshfield Clin Fdn Med Res & Educ, Dept Med Genet, Marshfield, WI USA.
[Brautbar, Ariel; Nambi, Vijay; Virani, Salim S.; Ballantyne, Christie M.] Baylor Coll Med, Dept Med, Houston, TX 77030 USA.
[Brautbar, Ariel] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA.
[Brautbar, Ariel; Nambi, Vijay; Virani, Salim S.; Ballantyne, Christie M.] Methodist DeBakey Heart & Vasc Ctr, Ctr Cardiovasc Dis Prevent, Houston, TX USA.
[Pompeii, Lisa A.; Boerwinkle, Eric] Univ Texas Hlth Sci Ctr Houston, Dept Epidemiol Human Genet & Environm Sci, Houston, TX USA.
[Dehghan, Abbas; Hofman, Albert; Witteman, Jacqueline C. M.] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.
[Dehghan, Abbas; Rivadeneira, Fernando; Uitterlinden, Andre G.; Hofman, Albert; Witteman, Jacqueline C. M.] Netherlands Genom Initiat, Netherlands Consortium Hlth Aging, Leiden, Netherlands.
[Ngwa, Julius S.; Pencina, Michael J.; Cupples, L. Adrienne] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Virani, Salim S.] Michael E DeBakey VA Med Ctr, Hlth Serv Res & Dev Ctr Excellence, Hlth Policy & Qual Program, Houston, TX USA.
[Rivadeneira, Fernando; Uitterlinden, Andre G.] Erasmus MC, Dept Internal Med, Rotterdam, Netherlands.
[Folsom, Aaron R.] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA.
[Cupples, L. Adrienne] NHLBI, Framingham Heart Study, Framingham, MA USA.
[Boerwinkle, Eric] Univ Texas Hlth Sci Ctr Houston, Human Genet Ctr, Houston, TX USA.
[Boerwinkle, Eric] Univ Texas Hlth Sci Ctr Houston, Inst Mol Med, Houston, TX USA.
RP Brautbar, A (reprint author), 6565 Fannin St,Suite A679,MS A-601, Houston, TX 77030 USA.
EM brautbar@bcm.edu
RI Rivadeneira, Fernando/O-5385-2015;
OI Rivadeneira, Fernando/0000-0001-9435-9441; Cupples, L.
Adrienne/0000-0003-0273-7965; Virani, Salim/0000-0001-9541-6954;
Dehghan, Abbas/0000-0001-6403-016X
FU National Heart, Lung, and Blood Institute [HHSN268201100005C,
HHSN268201100006C, HHSN26820110000-07C, HHSN268201100008C,
HHSN268201100009C, HHSN268201100010C, HHSN268201100011C,
HHSN268201100012C]; National Human Genome Research Institute
[U01HG004402]; NIH [HHSN268200625226C, 1P30HL101255-01, N01-HC-25195];
NIH Roadmap for Medical Research; Erasmus Medical Center and Erasmus
University, Rotterdam; Netherlands Organization for the Health Research
and Development (ZonMw); Research Institute for Diseases in the Elderly
(RIDE); Ministry of Education, Culture and Science; Ministry for Health,
Welfare and Sports; European Commission (DG XII); Municipality of
Rotterdam; Netherlands Organisation of Scientific Research NWO
Investments [175.010.2005.011, 911-03-012]; Research Institute for
Diseases in the Elderly [014-93-015, RIDE2]; Netherlands Genomics
Initiative (NGI)/Netherlands Consortium for Healthy Aging (NCHA)
[050-060-810]; NWO grant (Vici) [918-76-619]; [R01HL087641];
[R01HL59367]; [R01HL086694]; [UL1RR025005]
FX The ARIC Study is carried out as a collaborative study supported by
National Heart, Lung, and Blood Institute contracts (HHSN268201100005C,
HHSN268201100006C, HHSN26820110000-07C, HHSN268201100008C,
HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, and
HHSN268201100012C), R01HL087641, R01HL59367 and R01HL086694; National
Human Genome Research Institute contract U01HG004402; and NIH contract
HHSN268200625226C. Infrastructure was partly supported by grant
UL1RR025005, a component of the NIH and NIH Roadmap for Medical
Research. The Rotterdam Study is funded by Erasmus Medical Center and
Erasmus University, Rotterdam, Netherlands Organization for the Health
Research and Development (ZonMw), the Research Institute for Diseases in
the Elderly (RIDE), the Ministry of Education, Culture and Science, the
Ministry for Health, Welfare and Sports, the European Commission (DG
XII), and the Municipality of Rotterdam. Genotyping was funded by the
Netherlands Organisation of Scientific Research NWO Investments
(175.010.2005.011, 911-03-012), the Research Institute for Diseases in
the Elderly (014-93-015; RIDE2), the Netherlands Genomics Initiative
(NGI)/Netherlands Consortium for Healthy Aging (NCHA) project nr.
050-060-810. Abbas Dehghan is supported by NWO grant (Vici, 918-76-619).
Dr Brautbar is supported by NIH grant 1P30HL101255-01. The Framingham
Heart Study of the National Heart, Lung, and Blood Institute of the NIH
and Boston University School of Medicine is supported by NIH contract
N01-HC-25195.
NR 29
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U1 2
U2 7
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0021-9150
J9 ATHEROSCLEROSIS
JI Atherosclerosis
PD AUG
PY 2012
VL 223
IS 2
BP 421
EP 426
DI 10.1016/j.atherosclerosis.2012.05.035
PG 6
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 985CA
UT WOS:000307239800027
PM 22789513
ER
PT J
AU Rasimas, JJ
AF Rasimas, J. J.
TI "Bath Salts" and the Return of Serotonin Syndrome
SO JOURNAL OF CLINICAL PSYCHIATRY
LA English
DT Editorial Material
ID MEPHEDRONE; TOXICOLOGY; TOXICITY
C1 NIMH, Expt Therapeut & Pathophysiol Branch, Bethesda, MD 20892 USA.
RP Rasimas, JJ (reprint author), NIMH, Expt Therapeut & Pathophysiol Branch, 10 CRC,Room 7-5541,10 Ctr Dr,MSC 1282, Bethesda, MD 20892 USA.
EM rasimasj@mail.nih.gov
NR 13
TC 5
Z9 5
U1 0
U2 2
PU PHYSICIANS POSTGRADUATE PRESS
PI MEMPHIS
PA P O BOX 752870, MEMPHIS, TN 38175-2870 USA
SN 0160-6689
J9 J CLIN PSYCHIAT
JI J. Clin. Psychiatry
PD AUG
PY 2012
VL 73
IS 8
BP 1126
EP 1127
DI 10.4088/JCP.12com07965
PG 2
WC Psychology, Clinical; Psychiatry
SC Psychology; Psychiatry
GA 090SM
UT WOS:000315000300009
PM 22967775
ER
PT J
AU Nabha, L
Krishnan, S
Ramanathan, R
Mejia, R
Roby, G
Sheikh, V
Mcauliffe, I
Nutman, T
Sereti, I
AF Nabha, Linda
Krishnan, Sonya
Ramanathan, Roshan
Mejia, Rojelio
Roby, Gregg
Sheikh, Virginia
Mcauliffe, Isabel
Nutman, Thomas
Sereti, Irini
TI Prevalence of Strongyloides stercoralis in an urban US AIDS cohort
SO PATHOGENS AND GLOBAL HEALTH
LA English
DT Article
DE AIDS; Strongyloidiasis; Antiretroviral therapy
ID LUCIFERASE IMMUNOPRECIPITATION SYSTEMS; ACTIVE ANTIRETROVIRAL THERAPY;
IMMUNE RESTORATION; UNITED-STATES; EPIDEMIOLOGIC FEATURES; PARASITIC
INFECTIONS; HIV-INFECTION; DIAGNOSIS; DISEASE; PATIENT
AB Objectives: We examined the prevalence of Strongyloides stercoralis (Ss) infection in a cohort of AIDS patients from a US urban centre. We monitored our cohort for possible cases of dissemination or immune reconstitution inflammatory syndrome after antiretroviral therapy (ART) initiation.
Methods: One hundred and three HIV-infected participants were prospectively sampled from a cohort observational study of ART-naive HIV-1-infected patients with CD4 <= 100 T cells/mu l. Clinical symptoms, corticosteroid therapy, eosinophilia, CD4 count, and plasma HIV-RNA were reviewed. Sera were tested by an enzyme-linked immunosorbent assay (CrAg-ELISA) to crude Ss extract or to an Ss-specific recombinant protein (NIE) and by luciferase immunoprecipitation system assay (LIPS) for Ss-specific antibodies.
Results: Twenty-five per cent of study participants were Strongyloides seropositive by CrAg-ELISA and 62% had emigrated from Strongyloides-endemic areas. The remaining 38% of the seropositives were US born and tested negative by NIE and LIPS. CrAg-ELISA-positive participants had a median CD4 count of 22 T cells/mu l and a median HIV-RNA of 4.87 log(10) copies/ml. They presented with diarrhea (27%), abdominal pain (23%), and skin manifestations (35%) that did not differ from seronegative patients. Peripheral blood eosinophilia was common among seropositive patients (prevalence of 62% compared to 29% in seronegatives, P=0.004). Seropositive patients were treated with ivermectin. There were no cases of hyperinfection syndrome.
Discussion: Strongyloidiasis may be prevalent in AIDS patients in the USA who emigrated from Ss-endemic countries, but serology can be inconclusive, suggesting that empiric ivermectin therapy is a reasonable approach in AIDS patients originating from Strongyloides endemic areas.
C1 [Nabha, Linda] Georgetown Univ Hosp, Dept Infect Dis, Washington, DC 20007 USA.
[Krishnan, Sonya] NCI Frederick, SAIC Frederick Inc, Clin Res Directorate, Clin Monitoring Res Program, Frederick, MD USA.
[Ramanathan, Roshan; Mejia, Rojelio; Sereti, Irini] NIAID, Clin Parasitol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
[Ramanathan, Roshan; Mejia, Rojelio] NIAID, Helminth Immunol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
[Mcauliffe, Isabel] Ctr Dis Control & Prevent, Atlanta, GA USA.
RP Sereti, I (reprint author), NIAID, Clin Parasitol Sect, Parasit Dis Lab, NIH, 10 Ctr Dr,Bldg 10,Room 11B07A, Bethesda, MD 20892 USA.
EM isereti@niaid.nih.gov
NR 35
TC 3
Z9 3
U1 1
U2 4
PU MANEY PUBLISHING
PI LEEDS
PA STE 1C, JOSEPHS WELL, HANOVER WALK, LEEDS LS3 1AB, W YORKS, ENGLAND
SN 2047-7724
J9 PATHOG GLOB HEALTH
JI Pathog. Glob. Health
PD AUG
PY 2012
VL 106
IS 4
BP 238
EP 244
DI 10.1179/2047773212Y.0000000031
PG 7
WC Public, Environmental & Occupational Health; Parasitology; Tropical
Medicine
SC Public, Environmental & Occupational Health; Parasitology; Tropical
Medicine
GA 068IA
UT WOS:000313358500009
PM 23265425
ER
PT J
AU Demelash, A
Rudrabhatla, P
Pant, HC
Wang, XY
Amin, ND
McWhite, CD
Xu, NZ
Linnoila, RI
AF Demelash, Abeba
Rudrabhatla, Parvathi
Pant, Harish C.
Wang, Xiaoyang
Amin, Niranjana D.
McWhite, Claire D.
Xu Naizhen
Linnoila, R. Ilona
TI Achaete-scute homologue-1 (ASH1) stimulates migration of lung cancer
cells through Cdk5/p35 pathway
SO MOLECULAR BIOLOGY OF THE CELL
LA English
DT Article
ID CYCLIN-DEPENDENT KINASE-5; PANCREATIC BETA-CELLS; NEUROENDOCRINE
DIFFERENTIATION; PROLIFERATION; APOPTOSIS; ACTIVATOR; ADHESION; P35;
NEURONS; ACHAETE-SCUTE-HOMOLOG-1
AB Our previous data suggested that the human basic helix-loop-helix transcription factor achaete-scute homologue-1 (hASH1) may stimulate both proliferation and migration in the lung. In the CNS, cyclin-dependent kinase 5 (Cdk5) and its activator p35 are important for neuronal migration that is regulated by basic helix-loop-helix transcription factors. Cdk5/p35 may also play a role in carcinogenesis. In this study, we found that the neuronal activator p35 was commonly expressed in primary human lung cancers. Cdk5 and p35 were also expressed by several human lung cancer cell lines and coupled with migration and invasion. When the kinase activity was inhibited by the Cdk5 inhibitor roscovitine or dominant-negative (dn) Cdk5, the migration of lung cancer cells was reduced. In neuroendocrine cells expressing hASH1, such as a pulmonary carcinoid cell line, knocking down the gene expression by short hairpin RNA reduced the levels of Cdk5/p35, nuclear p35 protein, and migration. Furthermore, expression of hASH1 in lung adenocarcinoma cells normally lacking hASH1 increased p35/Cdk5 activity and enhanced cellular migration. We were also able to show that p35 was a direct target for hASH1. In conclusion, induction of Cdk5 activity is a novel mechanism through which hASH1 may regulate migration in lung carcinogenesis.
C1 [Demelash, Abeba; Wang, Xiaoyang; McWhite, Claire D.; Xu Naizhen; Linnoila, R. Ilona] NCI, Cell & Canc Biol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Rudrabhatla, Parvathi; Pant, Harish C.; Amin, Niranjana D.] NINDS, Neurochem Lab, NIH, Bethesda, MD 20892 USA.
RP Linnoila, RI (reprint author), NCI, Cell & Canc Biol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM linnoila@mail.nih.gov
OI McWhite, Claire/0000-0001-7346-3047
FU NCI Intramural Research Program of the National Institutes of Health
FX The authors thank Kathy Kelly for the discussions during the project.
The authors are also grateful to Kathy Keefe and Timothy Healy for their
help in proofreading the manuscript. This research was supported by the
NCI Intramural Research Program of the National Institutes of Health.
The authors are grateful to Steve Hewitt and Pierre Massion for
providing the tissue microarrays of human lung cancers.
NR 48
TC 28
Z9 28
U1 0
U2 1
PU AMER SOC CELL BIOLOGY
PI BETHESDA
PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA
SN 1059-1524
J9 MOL BIOL CELL
JI Mol. Biol. Cell
PD AUG 1
PY 2012
VL 23
IS 15
BP 2856
EP 2866
DI 10.1091/mbc.E10-12-1010
PG 11
WC Cell Biology
SC Cell Biology
GA 052SM
UT WOS:000312218700006
PM 22696682
ER
PT J
AU Trask, SD
Ogden, KM
Patton, JT
AF Trask, Shane D.
Ogden, Kristen M.
Patton, John T.
TI Interactions among capsid proteins orchestrate rotavirus particle
functions
SO CURRENT OPINION IN VIROLOGY
LA English
DT Article
ID MEMBRANE-PENETRATION PROTEIN; BLUETONGUE VIRUS; STRUCTURAL INSIGHTS;
ANGSTROM RESOLUTION; ATOMIC-STRUCTURE; BINDING DOMAIN; MESSENGER-RNA;
VP4 PROTEIN; SPIKE; VIRION
AB Rotaviruses are members of the Reoviridae family of nonenveloped viruses and important etiologic agents of acute gastroenteritis in infants and young children. In recent years, high-resolution structures of triple-layered rotavirus virions and the constituent proteins have provided valuable insights into functions. Of note, structural studies have revealed the position of the viral RNA-dependent RNA polymerase, VP1, within the inner capsid, which in turn provides clues about the location of the viral capping machinery and the route of viral transcript egress. Mechanisms by which the viral spike protein, VP4, mediates receptor binding and membrane penetration have also been aided by high-resolution structural studies. Future work may serve to fill the remaining gaps in understanding of rotavirus particle structure and function.
C1 [Trask, Shane D.; Ogden, Kristen M.; Patton, John T.] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Patton, JT (reprint author), NIAID, Infect Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM jpatton@niaid.nih.gov
RI Patton, John/P-1390-2014
FU Public Health Service award from National Institutes of Allergy and
Infectious Diseases, National Institutes of Health [Z01 AI000788]
FX The authors would like to thank Stephen Harrison and Ethan Settembre for
helpful discussions and for sharing unpublished data. This work was
supported by Public Health Service award Z01 AI000788 from the
Intramural Research Program of the National Institutes of Allergy and
Infectious Diseases, National Institutes of Health.
NR 43
TC 14
Z9 15
U1 0
U2 6
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1879-6257
J9 CURR OPIN VIROL
JI Curr. Opin. Virol.
PD AUG
PY 2012
VL 2
IS 4
BP 373
EP 379
DI 10.1016/j.coviro.2012.04.005
PG 7
WC Virology
SC Virology
GA 051FZ
UT WOS:000312112900002
PM 22595300
ER
PT J
AU Delviks-Frankenberry, K
Cingoz, O
Coffin, JM
Pathak, VK
AF Delviks-Frankenberry, Krista
Cingoez, Oya
Coffin, John M.
Pathak, Vinay K.
TI Recombinant origin, contamination, and de-discovery of XMRV
SO CURRENT OPINION IN VIROLOGY
LA English
DT Article
ID VIRUS-RELATED VIRUS; CHRONIC-FATIGUE-SYNDROME; PROSTATE-CANCER;
RETROVIRUS XMRV; UNITED-STATES; BLOOD-CELLS; NO EVIDENCE; INFECTIOUS
RETROVIRUS; INTEGRATION SITES; GENE-SEQUENCES
AB The discovery and de-discovery of the xenotropic murine leukemia virus-related virus (XMRV) has been a tumultuous roller-coaster ride for scientists and patients. The initial associations of XMRV with chronic fatigue syndrome and prostate cancer, while providing much hope and optimism, have now been discredited and/or retracted following overwhelming evidence that (1) numerous patient cohorts from around the world are XMRV-negative, (2) the initial reports of XMRV-positive patients were due to contamination with mouse DNA, XMRV plasmid DNA, or virus from the 22Rv1 cell line and (3) XMRV is a laboratory-derived virus generated in the mid 1990s through recombination during passage of a prostate tumor xenograft in immuno-compromised mice. While these developments are disappointing to scientists and patients, they provide a valuable road map of potential pitfalls to the would-be microbe hunters.
C1 [Delviks-Frankenberry, Krista; Pathak, Vinay K.] NCI, Viral Mutat Sect, HIV DRP, Frederick Natl Lab Canc Res, Frederick, MD 21701 USA.
[Cingoez, Oya; Coffin, John M.] Tufts Univ, Sackler Sch Grad Biomed Sci, Genet Program, Boston, MA 02111 USA.
RP Pathak, VK (reprint author), NCI, Viral Mutat Sect, HIV DRP, Frederick Natl Lab Canc Res, Frederick, MD 21701 USA.
EM vinay.pathak@nih.gov
RI Delviks-Frankenberry, Krista/M-4822-2013
FU National Cancer Institute and was a Research Professor of the American
Cancer Society [R37 CA089441]; FM Kirby Foundation
FX 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. The funders had no role in study
design, data collection and analysis, decision to publish, or
preparation of the manuscript. JMC was supported by research grant R37
CA089441 from the National Cancer Institute and was a Research Professor
of the American Cancer Society with support from the FM Kirby
Foundation.
NR 94
TC 17
Z9 17
U1 0
U2 7
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1879-6257
J9 CURR OPIN VIROL
JI Curr. Opin. Virol.
PD AUG
PY 2012
VL 2
IS 4
BP 499
EP 507
DI 10.1016/j.coviro.2012.06.009
PG 9
WC Virology
SC Virology
GA 051FZ
UT WOS:000312112900018
PM 22818188
ER
PT J
AU Wang, LY
Chen, SF
Zhao, Q
Hixson, JE
Rao, DC
Jaquish, CE
Huang, JF
Lu, XF
Chen, JC
Cao, J
Li, JX
Li, HF
He, J
Liu, DP
Gu, DF
AF Wang, Laiyuan
Chen, Shufeng
Zhao, Qi
Hixson, James E.
Rao, Dabeeru C.
Jaquish, Cashell E.
Huang, Jianfeng
Lu, Xiangfeng
Chen, Jichun
Cao, Jie
Li, Jianxin
Li, Hongfan
He, Jiang
Liu, De-Pei
Gu, Dongfeng
CA GenSalt Collaborative Res Grp
TI Association between genetic variants of the ADD1 and GNB3 genes and
blood pressure response to the cold pressor test in a Chinese Han
population: the GenSalt Study
SO HYPERTENSION RESEARCH
LA English
DT Article
DE alpha-adducin; blood pressure; cold pressor test; G protein;
single-nucleotide polymorphism
ID ALPHA-ADDUCIN; HYPERTENSION; INTERVENTION; PREDICTOR; ARTERIES; STRESS;
GENOME; MAPS
AB Genetic factors influence blood pressure (BP) response to the cold pressor test (CPT), which is a phenotype related to hypertension risk. We examined the association between variants of the alpha-adducin (ADD1) and guanine nucleotide binding protein (G protein) beta-polypeptide 3 (GNB3) genes and BP response to the CPT. A total of 1998 Han Chinese participants from the Genetic Epidemiology Network of Salt Sensitivity completed the CPT. The area under the curve (AUC) above the baseline BP during the CPT was used to measure the BP response. Twelve single-nucleotide polymorphisms (SNPs) of the ADD1 and GNB3 genes were selected and genotyped. Both single-marker and haplotype association analyses were conducted using linear mixed models. The rs17833172 and rs3775067 SNPs of the ADD1 gene and the rs4963516 SNP of the GNB3 gene were significantly associated with the BP response to CPT, even after adjusting for multiple testing. For the ADD1 gene, the AA genotype of SNP rs17833172 was associated with lower systolic BP (SBP) reactivity (P < 0.0001) and faster BP recovery (P = 0.0003). The TT genotype of rs3775067 was associated with slower SBP recovery (P = 0.004). For the GNB3 gene, the C allele of SNP rs4963516 was associated with faster diastolic BP recovery (P = 0.002) and smaller overall AUC (P = 0.003). Haplotype analysis indicated that the CCGC haplotype of ADD1 constructed by rs1263359, rs3775067, rs4961 and rs4963 was significantly associated with the BP response to CPT. These data suggest that genetic variants of the ADD1 and GNB3 genes may have important roles in BP response to the CPT. Future studies aimed at replicating these novel findings are warranted. Hypertension Research (2012) 35, 805-810; doi:10.1038/hr.2012.38; published online 5 April 2012
C1 [Wang, Laiyuan; Chen, Shufeng; Huang, Jianfeng; Lu, Xiangfeng; Chen, Jichun; Cao, Jie; Li, Jianxin; Li, Hongfan; Gu, Dongfeng] Chinese Acad Med Sci, Dept Evidence Based Med, Beijing 100037, Peoples R China.
[Wang, Laiyuan; Chen, Shufeng; Huang, Jianfeng; Lu, Xiangfeng; Chen, Jichun; Cao, Jie; Li, Jianxin; Li, Hongfan; Gu, Dongfeng] Chinese Acad Med Sci, Div Populat Genet, State Key Lab Cardiovasc Dis, Cardiovasc Inst, Beijing 100037, Peoples R China.
[Wang, Laiyuan; Chen, Shufeng; Huang, Jianfeng; Lu, Xiangfeng; Chen, Jichun; Cao, Jie; Li, Jianxin; Li, Hongfan; Gu, Dongfeng] Chinese Acad Med Sci, Fuwai Hosp, Natl Ctr Cardiovasc Dis, Beijing 100037, Peoples R China.
[Wang, Laiyuan; Chen, Shufeng; Huang, Jianfeng; Lu, Xiangfeng; Chen, Jichun; Cao, Jie; Li, Jianxin; Li, Hongfan; Liu, De-Pei; Gu, Dongfeng] Peking Union Med Coll, Beijing 100021, Peoples R China.
[Wang, Laiyuan; Gu, Dongfeng] Chinese Natl Human Genome Ctr Beijing, Beijing, Peoples R China.
[Zhao, Qi; He, Jiang] Tulane Univ, Dept Epidemiol, Sch Publ Hlth & Trop Med, New Orleans, LA USA.
[Hixson, James E.] Univ Texas Houston, Sch Publ Hlth, Ctr Human Genet, Houston, TX USA.
[Rao, Dabeeru C.] Washington Univ, Sch Med, Div Biostat, St Louis, MO 63110 USA.
[Jaquish, Cashell E.] NHLBI, Div Cardiovasc Dis Sci, Bethesda, MD 20892 USA.
[He, Jiang] Tulane Univ, Sch Med, Dept Med, New Orleans, LA 70112 USA.
[Liu, De-Pei] Chinese Acad Med Sci, Natl Lab Med Mol Biol, Inst Basic Med Sci, Beijing 100037, Peoples R China.
RP Wang, LY (reprint author), Chinese Acad Med Sci, Dept Evidence Based Med, 167 Beilishi Rd, Beijing 100037, Peoples R China.
EM wanglaiyuan@yahoo.com.cn
FU National Heart, Lung and Blood Institute, National Institutes of Health,
Bethesda, MD [U01HL072507, R01HL087263, R01HL090682]
FX The Genetic Epidemiology Network of Salt Sensitivity (GenSalt) is
supported by a cooperative agreement project grant (U01HL072507,
R01HL087263, and R01HL090682) from the National Heart, Lung and Blood
Institute, National Institutes of Health, Bethesda, MD.
NR 23
TC 1
Z9 1
U1 0
U2 5
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0916-9636
J9 HYPERTENS RES
JI Hypertens. Res.
PD AUG
PY 2012
VL 35
IS 8
BP 805
EP 810
DI 10.1038/hr.2012.38
PG 6
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 985XR
UT WOS:000307304300005
PM 22476228
ER
PT J
AU McKenna, MT
Wang, SJ
Nguyen, TB
Burns, JE
Petrick, N
Summers, RM
AF McKenna, Matthew T.
Wang, Shijun
Nguyen, Tan B.
Burns, Joseph E.
Petrick, Nicholas
Summers, Ronald M.
TI Strategies for improved interpretation of computer-aided detections for
CT colonography utilizing distributed human intelligence
SO MEDICAL IMAGE ANALYSIS
LA English
DT Article
DE Computed tomography colonography; Observer performance study;
Crowdsourcing; Distributed human intelligence; Video analysis
ID TOMOGRAPHIC VIRTUAL COLONOSCOPY; COLONIC POLYP DETECTION; OBSERVER
PERFORMANCE; COLORECTAL NEOPLASIA; STOOL
AB Computer-aided detection (CAD) systems have been shown to improve the diagnostic performance of CT colonography (CTC) in the detection of premalignant colorectal polyps. Despite the improvement, the overall system is not optimal. CAD annotations on true lesions are incorrectly dismissed, and false positives are misinterpreted as true polyps. Here, we conduct an observer performance study utilizing distributed human intelligence in the form of anonymous knowledge workers (KWs) to investigate human performance in classifying polyp candidates under different presentation strategies. We evaluated 600 polyp candidates from 50 patients, each case having at least one polyp >= 6 mm, from a large database of CTC studies. Each polyp candidate was labeled independently as a true or false polyp by 20 KWs and an expert radiologist. We asked each labeler to determine whether the candidate was a true polyp after looking at a single 3D-rendered image of the candidate and after watching a video fly-around of the candidate. We found that distributed human intelligence improved significantly when presented with the additional information in the video fly-around. We noted that performance degraded with increasing interpretation time and increasing difficulty, but distributed human intelligence performed better than our CAD classifier for "easy" and "moderate" polyp candidates. Further, we observed numerous parallels between the expert radiologist and the KWs. Both showed similar improvement in classification moving from single-image to video interpretation. Additionally, difficulty estimates obtained from the KWs using an expectation maximization algorithm correlated well with the difficulty rating assigned by the expert radiologist. Our results suggest that distributed human intelligence is a powerful tool that will aid in the development of CAD for CTC. (c) 2012 Published by Elsevier B.V.
C1 [McKenna, Matthew T.; Wang, Shijun; Nguyen, Tan B.; Burns, Joseph E.; Summers, Ronald M.] NIH, Imaging Biomarkers & Comp Aided Diag Lab, Ctr Clin, Bethesda, MD 20892 USA.
[Burns, Joseph E.] Univ Calif Irvine, Med Ctr, Dept Radiol Sci, Orange, CA 92868 USA.
[Petrick, Nicholas] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA.
RP Summers, RM (reprint author), NIH, Imaging Biomarkers & Comp Aided Diag Lab, Ctr Clin, Bldg 10,Room 1C224,MSC 1182, Bethesda, MD 20892 USA.
EM rms@nih.gov
FU National Institutes of Health, Clinical Center; US Food and Drug
Administration
FX The intramural research programs of the National Institutes of Health,
Clinical Center, and the US Food and Drug Administration supported this
work. We thank Perry J. Pickhardt, M.D., J. Richard Choi, ScD, MD and
William Schindler, DO, for supplying CTC data. The mention of commercial
entities, or commercial products, their sources, or their use in
connection with material reported herein is not to be construed as
either an actual or implied endorsement of such entities or products by
the Department of Health and Human Services.
NR 37
TC 6
Z9 6
U1 2
U2 9
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1361-8415
J9 MED IMAGE ANAL
JI Med. Image Anal.
PD AUG
PY 2012
VL 16
IS 6
BP 1280
EP 1292
DI 10.1016/j.media.2012.04.007
PG 13
WC Computer Science, Artificial Intelligence; Computer Science,
Interdisciplinary Applications; Engineering, Biomedical; Radiology,
Nuclear Medicine & Medical Imaging
SC Computer Science; Engineering; Radiology, Nuclear Medicine & Medical
Imaging
GA 018VH
UT WOS:000309694100016
PM 22705287
ER
PT J
AU Beydoun, MA
Beydoun, HA
Shroff, MR
Kitner-Triolo, MH
Zonderman, AB
AF Beydoun, May A.
Beydoun, Hind A.
Shroff, Monal R.
Kitner-Triolo, Melissa H.
Zonderman, Alan B.
TI Serum leptin, thyroxine and thyroid-stimulating hormone levels interact
to affect cognitive function among US adults: evidence from a large
representative survey
SO NEUROBIOLOGY OF AGING
LA English
DT Article
DE Leptin; Thyroxine; Thyroid stimulating hormone; Cognitive function;
Aging
ID HIPPOCAMPAL SYNAPTIC PLASTICITY; SUBCLINICAL HYPOTHYROIDISM;
ALZHEIMERS-DISEASE; HEALTH-STATUS; OLDER-ADULTS; BRAIN; MOOD; DEMENTIA;
DECLINE; OBESITY
AB Neuroanatomical connections point to possible interactions between areas influencing energy homeostasis and those influencing cognition. We assessed whether serum leptin, thyroxine, and thyroid stimulating hormone (TSH) levels are associated with and interact to influence cognitive performance among US adults. Data from the National Health and Nutrition Examination Survey III (1988-1994) were used. Measures included a battery of neuropsychological tests and serum leptin, thyroxine, and TSH levels (20-59-year-old: n = 1114-2665; 60-90-year-old: n = 1365-5519). Among those 20-59-year-old, the middle tertile of leptin (vs. first tertile) was inversely related to the number of errors on the symbol digits substitution test. Increased thyroxine level was associated with a poorer performance on the serial digits test in the 20-59-year-old, but a better performance on the math test in 60-90-year-old group. TSH was associated with poor performance on various tests in the 20-59-year-old, but better performance in the 60-90-year-old group. Significant antagonistic interactions were found in both age groups between thyroxine, TSH, and leptin for a number of tests, including between leptin and thyroxine in the 60-90-year-old group in their association with word recall-correct score. We found significant associations of our main exposures with cognitive function among US adults, going in opposite directions between age groups in the cases of thyroid hormonal levels, as well as some interactive effects between exposures. It is important to conduct prospective cohort studies to provide further insight into potential interventions that would assess interactive effects of various hormonal replacement regimens. Published by Elsevier Inc.
C1 [Beydoun, May A.] NIA, Lab Behav Neurosci, NIH, IRP,Biomed Res Ctr, Baltimore, MD 21224 USA.
[Beydoun, Hind A.] Eastern Virginia Med Sch, Grad Program Publ Hlth, Norfolk, VA 23501 USA.
[Shroff, Monal R.] Univ Michigan, Dept Epidemiol, Ann Arbor, MI 48109 USA.
RP Beydoun, MA (reprint author), NIA, Lab Behav Neurosci, NIH, IRP,Biomed Res Ctr, 251 Bayview Blvd,Suite 100,Room 04B118, Baltimore, MD 21224 USA.
EM baydounm@mail.nih.gov
OI Zonderman, Alan B/0000-0002-6523-4778
FU NIH, National Institute on Aging
FX The authors thank Drs. Lori L. Beason-Held and Alyssa Gamaldo for their
internal review of this manuscript. This research was supported entirely
by the Intramural Research Program of the NIH, National Institute on
Aging.
NR 66
TC 12
Z9 12
U1 0
U2 8
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0197-4580
J9 NEUROBIOL AGING
JI Neurobiol. Aging
PD AUG
PY 2012
VL 33
IS 8
BP 1730
EP 1743
DI 10.1016/j.neurobiolaging.2011.05.008
PG 14
WC Geriatrics & Gerontology; Neurosciences
SC Geriatrics & Gerontology; Neurosciences & Neurology
GA 969QN
UT WOS:000306070800023
PM 21763035
ER
PT J
AU Englund, E
Gustafson, L
Passant, U
Majounie, E
Renton, AE
Traynor, BJ
Rohrer, JD
Mok, K
Hardy, J
AF Englund, Elisabet
Gustafson, Lars
Passant, Ulla
Majounie, Elisa
Renton, Alan E.
Traynor, Bryan J.
Rohrer, Jonathan D.
Mok, Kin
Hardy, John
TI Familial Lund frontotemporal dementia caused by C9ORF72 hexanucleotide
expansion
SO NEUROBIOLOGY OF AGING
LA English
DT Article
DE Frontotemporal dementia; Genetics
ID AMYOTROPHIC-LATERAL-SCLEROSIS; LOBAR DEGENERATION; CRITERIA; REPEAT;
FTD; ALS
AB Frontotemporal dementia (FTD) as an important clinical entity was rediscovered in Lund and Manchester in the early 1990s. Here we show that the large Lund pedigree with behavioral variant of frontotemporal dementia previously described with this disorder has an expansion in the recently described C9ORF72 locus on chromosome 9. (C) 2012 Elsevier Inc. All rights reserved.
C1 [Mok, Kin; Hardy, John] Inst Neurol, Reta Lilla Weston Labs, London WC1N 3BG, England.
[Mok, Kin; Hardy, John] Inst Neurol, Dept Mol Neurosci, London WC1N 3BG, England.
[Englund, Elisabet] Lund Univ, Dept Pathol, Reg Labs Reg Skane, Lund, Sweden.
[Gustafson, Lars; Passant, Ulla] Lund Univ, Dept Geriatr Psychiat, Lund, Sweden.
[Majounie, Elisa; Renton, Alan E.; Traynor, Bryan J.] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
[Rohrer, Jonathan D.] UCL, UCL Inst Neurol, Dementia Res Ctr, Dept Neurodegenerat Dis, London, England.
RP Hardy, J (reprint author), Inst Neurol, Reta Lilla Weston Labs, Queen Sq, London WC1N 3BG, England.
EM j.hardy@ion.ucl.ac.uk
RI Hardy, John/C-2451-2009; Traynor, Bryan/G-5690-2010; Mok,
Kin/F-5860-2012;
OI Rohrer, Jonathan/0000-0002-6155-8417
FU Intramural Research Programs of the NIH, National Institute on Aging
[Z01-AG000949-02]; NINDS; MND Association
FX This work was supported in part by the Intramural Research Programs of
the NIH, National Institute on Aging (Z01-AG000949-02), and NINDS and by
an MND Association grant to Richard Orrell and J.H. These data are
included in an ongoing international survey of the prevalence of C9ORF72
expansions (BJT, JH). The Trolle-Wachtmeister Foundation supported E. E.
Research nurse Karin Nilsson, Ph.D., is acknowledged for many years of
follow-up and contact with the family members.
NR 18
TC 2
Z9 2
U1 0
U2 1
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 AUG
PY 2012
VL 33
IS 8
AR 1850.e13
DI 10.1016/j.neurobiolaging.2012.02.019
PG 4
WC Geriatrics & Gerontology; Neurosciences
SC Geriatrics & Gerontology; Neurosciences & Neurology
GA 969QN
UT WOS:000306070800056
PM 22483864
ER
PT J
AU Ferrari, R
Mok, K
Moreno, JH
Cosentino, S
Goldman, J
Pietrini, P
Mayeux, R
Tierney, MC
Kapogiannis, D
Jicha, GA
Murrell, JR
Ghetti, B
Wassermann, EM
Grafman, J
Hardy, J
Huey, ED
Momeni, P
AF Ferrari, Raffaele
Mok, Kin
Moreno, Jorge H.
Cosentino, Stephanie
Goldman, Jill
Pietrini, Pietro
Mayeux, Richard
Tierney, Michael C.
Kapogiannis, Dimitrios
Jicha, Gregory A.
Murrell, Jill R.
Ghetti, Bernardino
Wassermann, Eric M.
Grafman, Jordan
Hardy, John
Huey, Edward D.
Momeni, Parastoo
TI Screening for C9ORF72 repeat expansion in FTLD
SO NEUROBIOLOGY OF AGING
LA English
DT Article
DE FTLD; bv-FTD; FTD-ALS; C9ORF72; GRN; PSEN-2; Alzheimer's disease
ID AMYOTROPHIC-LATERAL-SCLEROSIS; FRONTOTEMPORAL LOBAR DEGENERATION;
HEXANUCLEOTIDE REPEAT; DIAGNOSTIC-CRITERIA; CHROMOSOME 9P; DEMENTIA;
ALS; GENE; FTD; CONSENSUS
AB In the present study we aimed to determine the prevalence of C9ORF72 GGGGCC hexanucleotide expansion in our cohort of 53 frontotemporal lobar degeneration (FTLD) patients and 174 neurologically normal controls. We identified the hexanucleotide repeat, in the pathogenic range, in 4 (2 bv-frontotemporal dementia (FTD) and 2 FTD-amyotrophic lateral sclerosis [ALS]) out of 53 patients and 1 neurologically normal control. Interestingly, 2 of the C9ORF72 expansion carriers also carried 2 novel missense mutations in GRN (Y294C) and in PSEN-2(I146V). Further, 1 of the C9ORF72 expansion carriers, for whom pathology was available, showed amyloid plaques and tangles in addition to TAR (trans-activation response) DNA-binding protein (TDP)-43 pathology. In summary, our findings suggest that the hexanucleotide expansion is probably associated with ALS, FTD, or FTD-ALS and occasional comorbid conditions such as Alzheimer's disease. These findings are novel and need to be cautiously interpreted and most importantly replicated in larger numbers of samples. Published by Elsevier Inc.
C1 [Ferrari, Raffaele; Moreno, Jorge H.; Momeni, Parastoo] Texas Tech Univ, Hlth Sci Ctr, Dept Internal Med, Neurogenet Lab, Lubbock, TX 79430 USA.
[Ferrari, Raffaele; Mok, Kin; Hardy, John] UCL, Inst Neurol, London, England.
[Cosentino, Stephanie; Goldman, Jill; Mayeux, Richard; Tierney, Michael C.; Kapogiannis, Dimitrios; Huey, Edward D.] Columbia Univ, Gertrude H Sergievsky Ctr, Taub Inst Res Alzheimers Dis & Aging Brain, New York, NY 10027 USA.
[Pietrini, Pietro] Univ Pisa, Sch Med, Lab Clin Biochem & Mol Biol, I-56100 Pisa, Italy.
[Wassermann, Eric M.; Grafman, Jordan; Huey, Edward D.] Natl Inst Neurol Disorders & Stroke, Cognit Neurosci Sect, NIH, Bethesda, MD USA.
[Kapogiannis, Dimitrios] NIA, Clin Res Branch, NIH, Bethesda, MD 20892 USA.
[Jicha, Gregory A.] Univ Kentucky, Sanders Brown Ctr Aging, Alzheimers Dis Ctr, Lexington, KY 40536 USA.
[Murrell, Jill R.; Ghetti, Bernardino] Indiana Univ Sch Med, Dept Pathol & Lab Med, Indiana Alzheimer Dis Ctr, Indianapolis, IN USA.
[Grafman, Jordan] Kessler Fdn Res Ctr, W Orange, NJ USA.
RP Momeni, P (reprint author), Texas Tech Univ, Hlth Sci Ctr, Dept Internal Med, Neurogenet Lab, 4C134,3601 4th St,STOP 9410, Lubbock, TX 79430 USA.
EM parastoo.momeni@ttuhsc.edu
RI Hardy, John/C-2451-2009; Mok, Kin/F-5860-2012;
OI Grafman, Jordan H./0000-0001-8645-4457
FU Alzheimer's Research UK; Intramural Research Programs of the National
Institute on Aging; National Institute of Neurological Disorders and
Stroke; NIH/NINDS [5R00NS060766]; NINDS Intramural Research Program; NIH
[PHS P30 AG 10133]; office of the Dean of the School of Medicine,
department of Internal Medicine, at Texas Tech Health Sciences Center
FX PM molecular genetics work is funded by the office of the Dean of the
School of Medicine, department of Internal Medicine, at Texas Tech
Health Sciences Center. J.H.'s work on FTD GWAS is supported partly by a
grant from Alzheimer's Research UK. This research was supported in part
by the Intramural Research Programs of the National Institute on Aging
and the National Institute of Neurological Disorders and Stroke.
E.D.H.'s work is supported by NIH/NINDS grant 5R00NS060766. J.G.'s work
is supported by the NINDS Intramural Research Program. D.G.'s work was
supported by NIH grant PHS P30 AG 10133. The authors thank Mike Hubank
and Kerra Pearce at the Genomic core facility at the Institute of Child
Health (ICH), University College London (UCL) for assisting R. F. in
performing Illumina genotyping experiments, and Cynthia Crews, Anne
Leopold, and Karen DeTucci for the study coordination.
NR 24
TC 2
Z9 2
U1 0
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0197-4580
J9 NEUROBIOL AGING
JI Neurobiol. Aging
PD AUG
PY 2012
VL 33
IS 8
AR 1850.e1
DI 10.1016/j.neurobiolaging.2012.02.017
PG 11
WC Geriatrics & Gerontology; Neurosciences
SC Geriatrics & Gerontology; Neurosciences & Neurology
GA 969QN
UT WOS:000306070800055
PM 22459598
ER
PT J
AU Lohmann, E
Guerreiro, RJ
Erginel-Unaltuna, N
Gurunlian, N
Bilgic, B
Gurvit, H
Hanagasi, HA
Luu, N
Emre, M
Singleton, A
AF Lohmann, Ebba
Guerreiro, Rita J.
Erginel-Unaltuna, Nihan
Gurunlian, Nicole
Bilgic, Basar
Gurvit, Hakan
Hanagasi, Hasmet A.
Luu, Nga
Emre, Murat
Singleton, Andrew
TI Identification of PSEN1 and PSEN2 gene mutations and variants in Turkish
dementia patients
SO NEUROBIOLOGY OF AGING
LA English
DT Article
DE Alzheimer disease; Presenilin; Mutation; Turkey
ID FAMILIAL ALZHEIMERS-DISEASE; PRECURSOR PROTEIN GENES; PRESENILIN-1 GENE;
MISSENSE MUTATIONS; COMMON VARIANTS; POPULATION; JAPANESE; ASSOCIATION;
PREVALENCE; EXPRESSION
AB In order to assess the frequency of mutations in the known Alzheimer's disease causative genes in Turkish dementia patients we screened amyloid precursor protein (APP), PSEN1 and PSEN2 for mutations in a cohort of 98 Turkish dementia families. Six families were found to carry PSEN1 mutations (p.H163R, p.P264L, and p.H214Y) or variants suggested to cause the disease (p.L134R, p.L262V, and p.A396T). In 4 other families, previously reported PSEN2 variants were identified (p.R62H, p.R71W, p.M174V (n = 2), and p.S130L). The phenotype of the carriers varied from rapid progressing Alzheimer's disease to frontotemporal dementia, with spasticity and seizures also observed. Here we report a frequency of 11.2% of mutations and variants in the known Alzheimer disease genes in the dementia cohort studied and 24% in the early onset subgroup of patients, suggesting that mutations in these genes are not uncommon in Turkey and are associated with various phenotypes. We thus believe that genetic analysis should become a standardized diagnostic implement, not only for the identification of the genetic disease, but also for appropriate genetic counseling. (C) 2012 Elsevier Inc. All rights reserved.
C1 [Lohmann, Ebba; Bilgic, Basar; Gurvit, Hakan; Hanagasi, Hasmet A.; Emre, Murat] Istanbul Univ, Fac Med, Dept Neurol, TR-30390 Istanbul, Turkey.
[Guerreiro, Rita J.] Univ Coimbra, Ctr Neurosci & Cell Biol, Coimbra, Portugal.
[Guerreiro, Rita J.; Gurunlian, Nicole] Inst Neurol, Dept Mol Neurosci, London WC1N 3BG, England.
[Guerreiro, Rita J.; Luu, Nga; Singleton, Andrew] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
[Erginel-Unaltuna, Nihan] Istanbul Univ, Inst Expt Med, TR-30390 Istanbul, Turkey.
RP Lohmann, E (reprint author), Istanbul Univ, Fac Med, Dept Neurol, TR-30390 Istanbul, Turkey.
EM ebbalohmann@gmx.net
RI Guerreiro, Rita/A-1327-2011; Singleton, Andrew/C-3010-2009; bilgic,
basar/E-4821-2012
FU Intramural Research Program of the National Institute on Aging, National
Institutes of Health, Department of Health and Human Services [Z01
AG000950-06]; National Institute on Aging (NIA) [U24 AG21886]
FX This work was supported in part by the Intramural Research Program of
the National Institute on Aging, National Institutes of Health,
Department of Health and Human Services, project number Z01 AG000950-06.
Samples from the National Cell Repository for Alzheimer's Disease
(NCRAD), which receives government support under a cooperative agreement
grant (U24 AG21886) awarded by the National Institute on Aging (NIA),
were used in this study.
NR 51
TC 7
Z9 11
U1 0
U2 5
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0197-4580
J9 NEUROBIOL AGING
JI Neurobiol. Aging
PD AUG
PY 2012
VL 33
IS 8
AR 1850.e17
DI 10.1016/j.neurobiolaging.2012.02.020
PG 11
WC Geriatrics & Gerontology; Neurosciences
SC Geriatrics & Gerontology; Neurosciences & Neurology
GA 969QN
UT WOS:000306070800057
PM 22503161
ER
PT J
AU Sabatelli, M
Conforti, FL
Zollino, M
Mora, G
Monsurro, MR
Volanti, P
Marinou, K
Salvi, F
Corbo, M
Giannini, F
Battistini, S
Penco, S
Lunetta, C
Quattrone, A
Gambardella, A
Logroscino, G
Simone, I
Bartolomei, I
Pisano, F
Tedeschi, G
Conte, A
Spataro, R
La Bella, V
Caponnetto, C
Mancardi, G
Mandich, P
Sola, P
Mandrioli, J
Renton, AE
Majounie, E
Abramzon, Y
Marrosu, F
Marrosu, MG
Murru, MR
Sotgiu, MA
Pugliatti, M
Rodolico, C
Moglia, C
Calvo, A
Ossola, I
Brunetti, M
Traynor, BJ
Borghero, G
Restagno, G
Chio, A
AF Sabatelli, Mario
Conforti, Francesca Luisa
Zollino, Marcella
Mora, Gabriele
Monsurro, Maria Rosaria
Volanti, Paolo
Marinou, Kalliopi
Salvi, Fabrizio
Corbo, Massimo
Giannini, Fabio
Battistini, Stefania
Penco, Silvana
Lunetta, Christian
Quattrone, Aldo
Gambardella, Antonio
Logroscino, Giancarlo
Simone, Isabella
Bartolomei, Ilaria
Pisano, Fabrizio
Tedeschi, Gioacchino
Conte, Amelia
Spataro, Rossella
La Bella, Vincenzo
Caponnetto, Claudia
Mancardi, Gianluigi
Mandich, Paola
Sola, Patrizia
Mandrioli, Jessica
Renton, Alan E.
Majounie, Elisa
Abramzon, Yevgeniya
Marrosu, Francesco
Marrosu, Maria Giovanna
Murru, Maria Rita
Sotgiu, Maria Alessandra
Pugliatti, Maura
Rodolico, Carmelo
Moglia, Cristina
Calvo, Andrea
Ossola, Irene
Brunetti, Maura
Traynor, Bryan J.
Borghero, Giuseppe
Restagno, Gabriella
Chio, Adriano
CA ITALSGEN Consortium
TI C9ORF72 hexanucleotide repeat expansions in the Italian sporadic ALS
population
SO NEUROBIOLOGY OF AGING
LA English
DT Article
DE Amyotrophic lateral sclerosis; C9ORF72; Frontotemporal dementia;
Survival
ID AMYOTROPHIC-LATERAL-SCLEROSIS; MUTATIONS; GENE; IDENTIFICATION; FUS; FTD
AB It has been recently reported that a large proportion of patients with familial amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are associated with a hexanucleotide (GGGGCC) repeat expansion in the first intron of C9ORF72. We have assessed 1757 Italian sporadic ALS cases, 133 from Sardinia, 101 from Sicily, and 1523 from mainland Italy. Sixty (3.7%) of 1624 mainland Italians and Sicilians and 9 (6.8%) of the 133 Sardinian sporadic ALS cases carried the pathogenic repeat expansion. None of the 619 regionally matched control samples (1238 chromosomes) carried the expansion. Twenty-five cases (36.2%) had behavioral FTD in addition to ALS. FTD or unspecified dementia was also detected in 19 pedigrees (27.5%) in first-degree relatives of ALS patients. Cases carrying the C9ORF72 hexanucleotide expansion survived 1 year less than cases who did not carry this mutation. In conclusion, we found that C9ORF72 hexanucleotide repeat expansions represents a sizeable proportion of apparent sporadic ALS in the Italian and Sardinian population, representing by far the most common mutation in Italy and the second most common in Sardinia. (C) 2012 Elsevier Inc. All rights reserved.
C1 [Moglia, Cristina; Calvo, Andrea; Chio, Adriano] Univ San Giovanni Battista Turin, Univ Turin, Azienda Osped, Dept Neurosci, Turin, Italy.
[Sabatelli, Mario; Conte, Amelia] Catholic Univ, Neurol Inst, Rome, Italy.
[Sabatelli, Mario; Conte, Amelia] ICOMM Assoc ALS Res, Rome, Italy.
[Conforti, Francesca Luisa; Quattrone, Aldo; Gambardella, Antonio] CNR, Inst Neurol Sci, Cosenza, Italy.
[Conforti, Francesca Luisa; Quattrone, Aldo; Gambardella, Antonio] Univ Magna Grecia, Catanzaro, Italy.
[Zollino, Marcella] Univ Cattolica Sacro Cuore, Mol Genet Lab, Rome, Italy.
[Mora, Gabriele; Marinou, Kalliopi] Sci Inst Milan, Salvatore Maugeri Fdn IRCSS, Milan, Italy.
[Monsurro, Maria Rosaria; Tedeschi, Gioacchino] Univ Naples 2, Dept Neurol Sci, Naples, Italy.
[Volanti, Paolo] Sci Inst Mistretta, Salvatore Maugeri Fdn IRCSS, Mistretta, Italy.
[Salvi, Fabrizio; Bartolomei, Ilaria] Bellaria Hosp, Dept Neurol, Ctr Diag & Cure Rare Dis, Bologna, Italy.
[Corbo, Massimo; Lunetta, Christian] Serena Fdn, Neuromuscular OnmiCtr, Milan, Italy.
[Giannini, Fabio; Battistini, Stefania] Univ Siena, Neurol Sect, Dept Neurosci, I-53100 Siena, Italy.
[Penco, Silvana] Osped Niguarda Ca Granda, Dept Lab Med, Milan, Italy.
[Logroscino, Giancarlo; Simone, Isabella] Univ Bari, Dept Neurosci, Bari, Italy.
[Pisano, Fabrizio] Sci Inst Veruno, Salvatore Maugeri Fdn IRCSS, Veruno, Italy.
[Spataro, Rossella; La Bella, Vincenzo] Univ Palermo, ALS Clin Res Ctr, Bio Ne C, Palermo, Italy.
[Caponnetto, Claudia; Mancardi, Gianluigi; Mandich, Paola] Univ Genoa, Dept Neurosci Ophthalmol & Genet, Genoa, Italy.
[Sola, Patrizia; Mandrioli, Jessica] St Agostino Estense Hosp, Dept Neurosci, Modena, Italy.
[Sola, Patrizia; Mandrioli, Jessica] Univ Modena, I-41100 Modena, Italy.
[Renton, Alan E.; Abramzon, Yevgeniya; Traynor, Bryan J.] NIA, Mol Genet Unit, Neurogenet Lab, Bethesda, MD 20892 USA.
[Majounie, Elisa] NIA, Neuromuscular Dis Res Unit, Neurogenet Lab, Bethesda, MD 20892 USA.
[Marrosu, Francesco; Borghero, Giuseppe] Azienda Univ Osped Cagliari, Cagliari, Italy.
[Marrosu, Francesco; Borghero, Giuseppe] Univ Cagliari, Cagliari, Italy.
[Marrosu, Maria Giovanna; Murru, Maria Rita] Univ Cagliari, Ctr Sclerosi Multipla, Osped Binaghi, Cagliari, Italy.
[Sotgiu, Maria Alessandra] Univ Sassari, Dept Biomed Sci, I-07100 Sassari, Italy.
[Pugliatti, Maura] Univ Sassari, Dept Neurosci, I-07100 Sassari, Italy.
[Rodolico, Carmelo] Univ Messina, Dept Neurosci Psychiat & Anaesthesiol Sci, Messina, Italy.
[Ossola, Irene; Brunetti, Maura; Restagno, Gabriella] ASO OIRM St Anna, Dept Clin Pathol, Mol Genet Unit, Turin, Italy.
RP Chio, A (reprint author), Univ Turin, Turin, Italy.
EM achio@usa.net
RI MANDRIOLI, JESSICA/K-7235-2016; Traynor, Bryan/G-5690-2010; Battistini,
Stefania/N-2596-2015; QUATTRONE, Aldo/A-6734-2016; Calvo,
Andrea/K-4141-2016; LOGROSCINO, GIANCARLO/K-5148-2016; Spataro,
Rossella/B-3656-2016; Lunetta, Christian/K-9214-2016; La Bella,
Vincenzo/H-4532-2012; Moglia, Cristina/K-4142-2016; mancardi, giovanni
luigi/K-8656-2016;
OI MANDRIOLI, JESSICA/0000-0002-9244-9782; Battistini,
Stefania/0000-0003-2887-7624; QUATTRONE, Aldo/0000-0003-2001-957X;
Calvo, Andrea/0000-0002-5122-7243; LOGROSCINO,
GIANCARLO/0000-0003-0423-3242; Spataro, Rossella/0000-0002-8910-3131;
Lunetta, Christian/0000-0002-4788-1875; Mandich,
Paola/0000-0003-3123-3512; Simone, Isabella Laura/0000-0002-7429-3091;
Sabatelli, Mario/0000-0001-6635-4985; Moglia,
Cristina/0000-0001-7377-7222; mancardi, giovanni
luigi/0000-0001-8427-118X; Chio, Adriano/0000-0001-9579-5341;
Cammarosano, Stefania/0000-0002-0981-5252; Penco,
Silvana/0000-0003-1050-095X; SOLINAS, GIULIANA/0000-0003-2174-0983;
RODOLICO, Carmelo/0000-0003-2543-6356; Marrosu, Maria
Giovanna/0000-0003-2334-2081; Gambardella , Antonio/0000-0001-7384-3074
FU Intramural Research Programs of the NIH, National Institute on Aging
[Z01-AG000949-02]; NINDS; Packard Center for ALS Research at Hopkins;
ALS Association; Microsoft Research; Federazione Italiana Giuoco Calcio;
European Community's Health Seventh Framework Programme [259867]; ARISLA
FX This work was supported in part by the Intramural Research Programs of
the NIH, National Institute on Aging (Z01-AG000949-02), and NINDS. The
work was also supported by the Packard Center for ALS Research at
Hopkins (BJT), the ALS Association (BJT, AC), Microsoft Research (BJT),
Federazione Italiana Giuoco Calcio (BJT, AC), European Community's
Health Seventh Framework Programme (FP7/2007-2013) under grant agreement
259867 (A.C), and ARISLA (BJT, AC).
NR 16
TC 7
Z9 7
U1 1
U2 11
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0197-4580
J9 NEUROBIOL AGING
JI Neurobiol. Aging
PD AUG
PY 2012
VL 33
IS 8
AR 1848.e15
DI 10.1016/j.neurobiolaging.2012.02.011
PG 6
WC Geriatrics & Gerontology; Neurosciences
SC Geriatrics & Gerontology; Neurosciences & Neurology
GA 969QN
UT WOS:000306070800052
PM 22418734
ER
PT J
AU Lund, JL
Sturmer, T
Sanoff, HK
Brookhart, A
Sandler, RS
Warren, JL
AF Lund, Jennifer L.
Stuermer, Til
Sanoff, Hanna K.
Brookhart, Alan
Sandler, Robert S.
Warren, Joan L.
TI Influence of Patient, Physician, and Hospital Characteristics on
Oxaliplatin Receipt among Older Stage II and III Colorectal Cancer
Patients in the US
SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY
LA English
DT Meeting Abstract
C1 [Lund, Jennifer L.; Stuermer, Til; Brookhart, Alan] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA.
[Sanoff, Hanna K.] Univ Virginia, Sch Med, Div Hematol & Oncol, Charlottesville, VA 22908 USA.
[Sandler, Robert S.] Univ N Carolina, Sch Med, Dept Med, Chapel Hill, NC USA.
[Warren, Joan L.] NCI, Hlth Serv & Econ Branch, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
RI Lund, Jennifer/G-9420-2012
NR 0
TC 0
Z9 0
U1 0
U2 1
PU WILEY PERIODICALS, INC
PI SAN FRANCISCO
PA ONE MONTGOMERY ST, SUITE 1200, SAN FRANCISCO, CA 94104 USA
SN 1053-8569
J9 PHARMACOEPIDEM DR S
JI Pharmacoepidemiol. Drug Saf.
PD AUG
PY 2012
VL 21
SU 3
SI SI
MA 155
BP 75
EP 75
PG 1
WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy
SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy
GA 996YU
UT WOS:000308131701152
ER
PT J
AU Gardarsdottir, H
Sauer, BC
Liang, HF
Ryan, P
Klungel, O
Reynolds, R
AF Gardarsdottir, Helga
Sauer, Brian C.
Liang, Huifang
Ryan, Patrick
Klungel, Olaf
Reynolds, Robert
TI Transparent, Reproducible and Reusable Research in Pharmacoepidemiology
SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY
LA English
DT Meeting Abstract
C1 [Gardarsdottir, Helga] Univ Med Ctr Utrecht, Dept Clin Pharm, Utrecht, Netherlands.
[Gardarsdottir, Helga; Klungel, Olaf] Univ Utrecht, Div Pharmacoepidemiol & Clin Pharmacol, Utrecht Inst Pharmaceut Sci, Utrecht, Netherlands.
[Sauer, Brian C.] SLC VA IDEAS Ctr, Salt Lake City, UT USA.
[Sauer, Brian C.] Univ Utah, Div Epidemiol, Salt Lake City, UT USA.
[Liang, Huifang] Takeda Global Res & Dev Ctr Inc, Deerfield, IL USA.
[Ryan, Patrick] Johnson & Johnson Pharmaceut Res & Dev LLC, Titusville, NJ USA.
[Ryan, Patrick] Fdn Natl Inst Hlth, Bethesda, MD USA.
[Reynolds, Robert] Pfizer, New York, NY USA.
[Reynolds, Robert] Tulane Univ, Sch Publ Hlth & Trop Med, New Orleans, LA USA.
RI Klungel, Olaf/I-9563-2016
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY PERIODICALS, INC
PI SAN FRANCISCO
PA ONE MONTGOMERY ST, SUITE 1200, SAN FRANCISCO, CA 94104 USA
SN 1053-8569
J9 PHARMACOEPIDEM DR S
JI Pharmacoepidemiol. Drug Saf.
PD AUG
PY 2012
VL 21
SU 3
SI SI
MA 416
BP 197
EP 197
PG 1
WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy
SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy
GA 996YU
UT WOS:000308131701404
ER
PT J
AU Tsai, HT
Isaacs, C
Makgoeng, S
Freedman, AN
Smith, SW
Warren, JL
Potosky, AL
AF Tsai, Huei-Ting
Isaacs, Claudine
Makgoeng, Solomon
Freedman, Andrew N.
Smith, Sheila Weiss
Warren, Joan L.
Potosky, Arnie L.
TI Risk of Congestive Heart Failure from Trastuzumab (Herceptin) in Elderly
Persons with Breast Cancer: A Population-Based Study
SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY
LA English
DT Meeting Abstract
C1 [Tsai, Huei-Ting; Isaacs, Claudine; Makgoeng, Solomon; Potosky, Arnie L.] Georgetown Univ, Med Ctr, Dept Oncol, Washington, DC 20007 USA.
[Freedman, Andrew N.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Smith, Sheila Weiss; Warren, Joan L.] Univ Maryland, Sch Pharm, Baltimore, MD 21201 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY PERIODICALS, INC
PI SAN FRANCISCO
PA ONE MONTGOMERY ST, SUITE 1200, SAN FRANCISCO, CA 94104 USA
SN 1053-8569
J9 PHARMACOEPIDEM DR S
JI Pharmacoepidemiol. Drug Saf.
PD AUG
PY 2012
VL 21
SU 3
SI SI
MA 740
BP 344
EP 344
PG 1
WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy
SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy
GA 996YU
UT WOS:000308131701712
ER
PT J
AU Wilson, JC
Murray, LJ
Hughes, CM
Black, A
Anderson, LA
AF Wilson, Jessica C.
Murray, Liam J.
Hughes, Carmel M.
Black, Amanda
Anderson, Lesley A.
TI Non-Steroidal Anti-Inflammatory Drug and Aspirin Use and the Risk of
Head and Neck Cancer
SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY
LA English
DT Meeting Abstract
C1 [Wilson, Jessica C.; Murray, Liam J.; Hughes, Carmel M.; Anderson, Lesley A.] Queens Univ Belfast, Belfast, Antrim, North Ireland.
[Black, Amanda] NCI, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU WILEY PERIODICALS, INC
PI SAN FRANCISCO
PA ONE MONTGOMERY ST, SUITE 1200, SAN FRANCISCO, CA 94104 USA
SN 1053-8569
J9 PHARMACOEPIDEM DR S
JI Pharmacoepidemiol. Drug Saf.
PD AUG
PY 2012
VL 21
SU 3
SI SI
MA 903
BP 418
EP 419
PG 2
WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy
SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy
GA 996YU
UT WOS:000308131701866
ER
PT J
AU Pernica, JM
LeBlanc, JC
Soto-Castellares, G
Donroe, J
Carhuancho-Meza, BA
Rainham, DGC
Gilman, RH
AF Pernica, Jeffrey M.
LeBlanc, John C.
Soto-Castellares, Giselle
Donroe, Joseph
Carhuancho-Meza, Bristan A.
Rainham, Daniel G. C.
Gilman, Robert H.
TI Risk factors predisposing to pedestrian road traffic injury in children
living in Lima, Peru: a case-control study
SO ARCHIVES OF DISEASE IN CHILDHOOD
LA English
DT Article
ID MOTOR-VEHICLE CRASHES; BEHAVIORAL-FACTORS; URBAN; CHILDHOOD; ACCIDENTS;
TRENDS
AB Objective To describe the epidemiology of pedestrian road traffic injury in Lima and to identify associated child-level, family-level, and school travel-related variables.
Design Case-control study.
Setting The Instituto Nacional de Salud del Nino, the largest paediatric hospital in the city.
Participants Cases were children who presented because of pedestrian road traffic injury. Controls presented with other diagnoses and were matched on age, sex and severity of injury.
Results Low socioeconomic status, low paternal education, traffic exposure during the trip to school, lack of supervision during outside play, and duration of outside play were all statistically significantly associated with case-control status. In multivariate logistic regression, a model combining the lack of supervision during outside play and the number of the streets crossed walking to school best predicted case-control status (p<0.001).
Conclusions These results emphasise that an assessment of children's play behaviours and school locations should be considered and integrated into any plan for an intervention designed to reduce pedestrian road traffic injury. A child-centred approach will ensure that children derive maximum benefit from sorely needed public health interventions.
C1 [LeBlanc, John C.] Dalhousie Univ, Dept Pediat, IWK Hlth Ctr, Halifax, NS, Canada.
[Pernica, Jeffrey M.] McMaster Univ, Dept Pediat, Hamilton, ON, Canada.
[Soto-Castellares, Giselle; Donroe, Joseph; Gilman, Robert H.] Asociac Benef PRISMA, Lima, Peru.
[Soto-Castellares, Giselle] USN, Med Res Unit 6, Dept Emerging Infect Dis, Lima, Peru.
[Donroe, Joseph] Ellison Med Fdn, Fogarty Int Ctr, Boston, MA USA.
[Carhuancho-Meza, Bristan A.] Inst Nacl Salud Nino, Lima, Peru.
[Rainham, Daniel G. C.] Univ Ottawa, Inst Populat Hlth, Ottawa, ON, Canada.
[Gilman, Robert H.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD USA.
RP LeBlanc, JC (reprint author), Dalhousie Univ, Dept Pediat, IWK Hlth Ctr, 5850 Univ Ave, Halifax, NS, Canada.
EM John.LeBlanc@dal.ca
FU IWK Health Centre Research Office, Halifax, NS, Canada; American Academy
of Pediatrics
FX Funding IWK Health Centre Research Office, Halifax, NS, Canada. The
American Academy of Pediatrics.
NR 34
TC 2
Z9 2
U1 1
U2 17
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0003-9888
J9 ARCH DIS CHILD
JI Arch. Dis. Child.
PD AUG
PY 2012
VL 97
IS 8
BP 709
EP 713
DI 10.1136/archdischild-2011-300997
PG 5
WC Pediatrics
SC Pediatrics
GA 983DZ
UT WOS:000307100000007
PM 22685050
ER
PT J
AU Liu, YF
Ye, YH
AF Liu, Yanfen
Ye, Yihong
TI Roles of p97-Associated Deubiquitinases in Protein Quality Control at
the Endoplasmic Reticulum
SO CURRENT PROTEIN & PEPTIDE SCIENCE
LA English
DT Review
DE p97/VCP/Cdc48; ERAD/retrotranslocation; deubiquitination; ataxin-3;
YOD1; proteasome; ubiquitin; ER protein quality control
ID ER-ASSOCIATED DEGRADATION; E3 UBIQUITIN LIGASE; RECOGNIZES SUGAR CHAINS;
AAA ATPASE CDC48/P97; ENZYME ATAXIN-3; PROTEASOMAL DEGRADATION;
POLYUBIQUITIN CHAINS; CONJUGATING ENZYME; MEMBRANE-PROTEIN; 26S
PROTEASOME
AB To maintain protein homeostasis in the ER, an ER protein quality control system retains unfolded polypeptides and misassembled membrane proteins, allowing only properly folded proteins to exit the ER. Misfolded proteins held in the ER are retrotranslocated into the cytosol, ubiquitinated, and degraded by the proteasome through the ER-associated degradation pathway (ERAD). By timely eliminating misfolded proteins, the ERAD system alleviates cytotoxic stress imposed by protein misfolding. It is well established that ER-associated ubiquitin ligases play pivotal roles in ERAD by assembling ubiquitin conjugates on retrotranslocation substrates, which serve as degradation signals for the proteasome. Surprisingly, recent studies have revealed an equally important function for deubiquitinases (DUBs), enzymes that disassemble ubiquitin chains, in ERAD. Intriguingly, many ERAD specific DUBs are physically associated with the retrotrans-location-driving ATPase p97. Here we discuss the potential functions of p97-associated DUBs including ataxin-3 and YOD1. Our goal is to integrate the emerging evidence into models that may explain how protein quality control could benefit from deubiquitination, a process previously deemed destructive for proteasomal degradation.
C1 [Liu, Yanfen; Ye, Yihong] NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Ye, YH (reprint author), NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
EM yihongy@mail.nih.gov
FU NIH intramural AIDS Targeted Antiviral Program (IATAP); National
Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
FX The authors declare no competing financial interests. The authors'
research is supported by the NIH intramural AIDS Targeted Antiviral
Program (IATAP) and by the Intramural Research Program of the National
Institute of Diabetes and Digestive and Kidney Diseases (NIDDK).
NR 99
TC 20
Z9 21
U1 0
U2 19
PU BENTHAM SCIENCE PUBL LTD
PI SHARJAH
PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB
EMIRATES
SN 1389-2037
EI 1875-5550
J9 CURR PROTEIN PEPT SC
JI Curr. Protein Pept. Sci.
PD AUG
PY 2012
VL 13
IS 5
BP 436
EP 446
PG 11
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 022RC
UT WOS:000309978300004
PM 22812527
ER
PT J
AU Guha, R
AF Guha, Rajarshi
TI Exploring Uncharted Territories: Predicting Activity Cliffs in
Structure-Activity Landscapes
SO JOURNAL OF CHEMICAL INFORMATION AND MODELING
LA English
DT Article
ID INDEX
AB The notion of activity cliffs is an intuitive approach to characterizing structural features that play a key role in modulating biological activity of a molecule. A variety of methods have been described to quantitatively characterize activity cliffs, such as SAL! and SARI However, these methods are primarily retrospective in nature; highlighting cliffs that are already present in the data set. The current study focuses on employing a pairwise characterization of a data set to train a model to predict whether a new molecule will exhibit an activity cliff, with one or more members of the data set. The approach is based on predicting a value for pairs of objects rather than the individual objects themselves (and thus allows for robust models even for small structure-activity relationship data sets). We extracted structure-activity data for several ChEMBL assays and developed random forest models to predict SALI values, from pairwise combinations of molecular descriptors. The models exhibited reasonable RMSE's though, surprisingly, performance on the more significant cliffs tended to be better than on the lesser ones. While the models do not exhibit very high levels of accuracy, our results indicate that they are able to prioritize molecules in terms of their ability to activity cliffs, thus serving as a tool to prospectively identify activity cliffs.
C1 NIH, Ctr Adv Translat Sci, Rockville, MD 20850 USA.
RP Guha, R (reprint author), NIH, Ctr Adv Translat Sci, 9800 Med Ctr Dr, Rockville, MD 20850 USA.
OI Guha, Rajarshi/0000-0001-7403-8819
FU Intramural NIH HHS [ZIB HG200319-08]
NR 24
TC 20
Z9 20
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1549-9596
J9 J CHEM INF MODEL
JI J. Chem Inf. Model.
PD AUG
PY 2012
VL 52
IS 8
BP 2181
EP 2191
DI 10.1021/ci300047k
PG 11
WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Computer Science,
Information Systems; Computer Science, Interdisciplinary Applications
SC Pharmacology & Pharmacy; Chemistry; Computer Science
GA 998PZ
UT WOS:000308254200028
PM 22873578
ER
PT J
AU Engin, HB
Keskin, O
Nussinov, R
Gursoy, A
AF Engin, H. Billur
Keskin, Ozlem
Nussinov, Ruth
Gursoy, Attila
TI A Strategy Based on Protein-Protein Interface Motifs May Help in
Identifying Drug Off-Targets
SO JOURNAL OF CHEMICAL INFORMATION AND MODELING
LA English
DT Article
ID LIGAND-BINDING-SITES; FIT BACKBONE REFINEMENT; DEPENDENT KINASE CDK6;
P53 NETWORK; INTERACTION DATABASE; MOLECULAR DOCKING; CRYSTAL-STRUCTURE;
ATTACK TOLERANCE; STRUCTURAL BASIS; SYSTEMS BIOLOGY
AB Networks are increasingly used to study the impact of drugs at the systems level. From the algorithmic standpoint, a drug can "attack" nodes or edges of a protein-protein interaction network In this work, we propose a new network strategy, "The Interface Attack", based on protein-protein interfaces. Similar interface architectures can occur between unrelated proteins. Consequently, in principle, a drug that binds to one has a certain probability of binding to others. The interface attack strategy simultaneously removes from the network all interactions that consist of similar interface motifs. This strategy is inspired by network pharmacology and allows inferring potential off-targets. We introduce a network model that we call "Protein Interface and Interaction Network (P2IN)", which is the integration of protein-protein interface structures and protein interaction networks. This interface based, network organization clarifies which protein pairs have structurally similar interfaces and which proteins may compete to bind the same surface region. We built the P2IN with the p53 signaling network and performed network robustness analysis. We show that (1) "hitting" frequent interfaces (a set of edges distributed around the network) might be as destructive as eleminating high degree proteins (hub nodes), (2) frequent interfaces are not always topologically critical elements in the network, and (3) interface attack may reveal functional changes in the system better than the attack of single proteins. In the off target detection case study, we found that drugs blocking the interface between CDK6 and CDKN2D may also affect the interaction between CDK4 and CDKN2D.
C1 [Engin, H. Billur; Keskin, Ozlem; Gursoy, Attila] Koc Univ, Ctr Computat Biol & Bioinformat, TR-34450 Istanbul, Turkey.
[Engin, H. Billur; Keskin, Ozlem; Gursoy, Attila] Koc Univ, Coll Engn, TR-34450 Istanbul, Turkey.
[Nussinov, Ruth] SAIC Frederick, Frederick Natl Lab Canc Res, Ctr Canc Res Nanobiol Program, Frederick, MD 21702 USA.
[Nussinov, Ruth] Tel Aviv Univ, Sackler Sch Med, Sackler Inst Mol Med, IL-69978 Tel Aviv, Israel.
RP Gursoy, A (reprint author), Koc Univ, Ctr Computat Biol & Bioinformat, Rumelifeneri Yolu, TR-34450 Istanbul, Turkey.
EM agursoy@ku.edu.tr
RI Gursoy, Attila/E-9565-2015
OI Gursoy, Attila/0000-0002-2297-2113
FU TUBITAK [109T343, 109E207]; Turkish Academy of Sciences (TUBA); National
Cancer Institute, National Institutes of Health [HHSN261200800001E];
Intramural Research Program of the NIH, National Cancer Institute,
Center for Cancer Research
FX This work is supported by TUBITAK (Research Grant Numbers 109T343 and
109E207) and Turkish Academy of Sciences (TUBA). This project is funded
in whole or in part with federal funds from the National Cancer
Institute, National Institutes of Health, under contract number
HHSN261200800001E. The content of this publication does not necessarily
reflect the views or policies of the Department of Health and Human
Services, nor does mention of trade names, commercial products, or
organizations imply endorsement by the U.S. Government. This research is
supported (in part) by the Intramural Research Program of the NIH,
National Cancer Institute, Center for Cancer Research.
NR 103
TC 16
Z9 16
U1 1
U2 21
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1549-9596
J9 J CHEM INF MODEL
JI J. Chem Inf. Model.
PD AUG
PY 2012
VL 52
IS 8
BP 2273
EP 2286
DI 10.1021/ci300072q
PG 14
WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Computer Science,
Information Systems; Computer Science, Interdisciplinary Applications
SC Pharmacology & Pharmacy; Chemistry; Computer Science
GA 998PZ
UT WOS:000308254200036
PM 22817115
ER
PT J
AU Fowler, DH
AF Fowler, Daniel H.
TI Protean effects of IL-10 include skin self-defense
SO JOURNAL OF LEUKOCYTE BIOLOGY
LA English
DT Editorial Material
C1 NCI, Bethesda, MD 20892 USA.
RP Fowler, DH (reprint author), NCI, 10 Ctr Dr,3-E Labs 3-3330, Bethesda, MD 20892 USA.
EM dhfowler@helix.nih.gov
NR 11
TC 0
Z9 0
U1 0
U2 0
PU FEDERATION AMER SOC EXP BIOL
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA
SN 0741-5400
J9 J LEUKOCYTE BIOL
JI J. Leukoc. Biol.
PD AUG
PY 2012
VL 92
IS 2
BP 247
EP 248
DI 10.1189/jlb.0312156
PG 3
WC Cell Biology; Hematology; Immunology
SC Cell Biology; Hematology; Immunology
GA 983MJ
UT WOS:000307123100002
PM 22850765
ER
PT J
AU Yancoski, J
Sadat, MA
Aksentijevich, N
Bernasconi, A
Holland, SM
Rosenzweig, SD
AF Yancoski, Judith
Sadat, Mohammed A.
Aksentijevich, Nadia
Bernasconi, Andrea
Holland, Steven M.
Rosenzweig, Sergio D.
TI A novel internalization motif regulates human IFN-gamma R1 endocytosis
SO JOURNAL OF LEUKOCYTE BIOLOGY
LA English
DT Article
DE tyrosine-based endocytosis motifs; dileucine-based endocytosis motifs;
recycling; transmembrane proteins
ID HUMAN INTERFERON-GAMMA; IFN-GAMMA; RECEPTOR; DOMINANT; EXPRESSION;
MURINE; INTERFERON-GAMMA-RECEPTOR-1; DEGRADATION; SEQUENCE; MUTATION
AB This study tested the hypothesis that the IFN-gamma R1 287-YVSLI-91 intracellular motif regulates its endocytosis. IFN-gamma exerts its biological activities by interacting with a specific cell-surface RC composed of two IFN-gamma R1 and two IFN-gamma R1 chains. Following IFN-gamma binding and along with the initiation of signal transduction, the ligand and IFN-gamma R1 are internalized. Two major types of consensus-sorting signals are described in receptors, which are rapidly internalized from the plasma membrane to intracellular compartments: tyrosine-based and dileucine-based internalization motifs. Transfection of HEK 293 cells and IFN-gamma R1-deficient fibroblasts with WT and site-directed, mutagenesis-generated mutant IFN-gamma R1 expression vectors helped us to identify region IFN-gamma R1 287-YVSLI-291 as the critical domain required for IFN-gamma-induced IFN-gamma R1 internalization and Y287 and LI290-291 as part of a common structure essential for receptor endocytosis and function. This new endocytosis motif, YxxLI, shares characteristics of tyrosine-based and dileucine-based internalization motifs and is highly conserved in IFN-gamma Rs across species. The IFN-gamma R1 270-LI-271 dileucine motif, previously thought to be involved in this receptor endocytosis, showed to be unnecessary for receptor endocytosis. J. Leukoc. Biol. 92: 301-308; 2012.
C1 [Sadat, Mohammed A.; Aksentijevich, Nadia; Rosenzweig, Sergio D.] NIAID, Infect Dis Susceptibil Unit, LHD, NIH, Bethesda, MD 20892 USA.
[Yancoski, Judith; Bernasconi, Andrea] Hosp Nacl Pediat JP Garrahan, Serv Inmunol & Reumatol, Buenos Aires, DF, Argentina.
[Holland, Steven M.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
RP Rosenzweig, SD (reprint author), NIAID, Infect Dis Susceptibil Unit, LHD, NIH, 10 Ctr Dr,CRC 6W-3750, Bethesda, MD 20892 USA.
EM srosenzweig@niaid.nih.gov
FU NIH Fogarty International Center; Fogarty International Research
Collaboration Award [R01TW006644]; NIAID, NIH
FX J.Y. and S.D.R. were supported in part by the NIH Fogarty International
Center and by the Fogarty International Research Collaboration Award
grant R01TW006644. This research was supported in part by the Intramural
Research Program of NIAID, NIH. S.D.R. thanks Dr. Stephanie
Boisson-Dupuis and Dr. Jean-Laureant Casanova (St. Giles Laboratory of
Human Genetics of Infectious Diseases, Rockefeller Branch, The
Rockefeller University, New York, NY, USA) for kindly sharing their
IFN-gamma R1-deficient cells and their comments with us and also, Nadia
Hussein for editing the final version of the manuscript.
NR 25
TC 4
Z9 4
U1 0
U2 1
PU FEDERATION AMER SOC EXP BIOL
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA
SN 0741-5400
J9 J LEUKOCYTE BIOL
JI J. Leukoc. Biol.
PD AUG
PY 2012
VL 92
IS 2
BP 301
EP 308
DI 10.1189/jlb.0212057
PG 8
WC Cell Biology; Hematology; Immunology
SC Cell Biology; Hematology; Immunology
GA 983MJ
UT WOS:000307123100008
PM 22595141
ER
PT J
AU Graves, SF
Kobayashi, SD
Braughton, KR
Whitney, AR
Sturdevant, DE
Rasmussen, DL
Kirpotina, LN
Quinn, MT
DeLeo, FR
AF Graves, Shawna F.
Kobayashi, Scott D.
Braughton, Kevin R.
Whitney, Adeline R.
Sturdevant, Daniel E.
Rasmussen, Devon L.
Kirpotina, Liliya N.
Quinn, Mark T.
DeLeo, Frank R.
TI Sublytic concentrations of Staphylococcus aureus Panton-Valentine
leukocidin alter human PMN gene expression and enhance bactericidal
capacity
SO JOURNAL OF LEUKOCYTE BIOLOGY
LA English
DT Article
DE MRSA; priming; neutrophil
ID HUMAN POLYMORPHONUCLEAR LEUKOCYTES; TUMOR-NECROSIS-FACTOR;
HUMAN-NEUTROPHILS; RECEPTOR (TLR)2; UNITED-STATES; GM-CSF; ACTIVATION;
LIPOPOLYSACCHARIDE; BINDING; PHAGOCYTOSIS
AB CA-MRSA infections are often caused by strains encoding PVL, which can cause lysis of PMNs and other myeloid cells in vitro, a function considered widely as the primary means by which PVL might contribute to disease. However, at sublytic concentrations, PVL can function as a PMN agonist. To better understand this phenomenon, we investigated the ability of PVL to alter human PMN function. PMNs exposed to PVL had enhanced capacity to produce O-2 (-) in response to fMLF, but unlike priming by LPS, this response did not require TLR signal transduction. On the other hand, there was subcellular redistribution of NADPH oxidase components in PMNs following exposure of these cells to PVL-a finding consistent with priming. Importantly, PMNs primed with PVL had an enhanced ability to bind/ ingest and kill Staphylococcus aureus. Priming of PMNs with other agonists, such as IL-8 or GM-CSF, altered the ability of PVL to cause formation of pores in the plasma membranes of these cells. Microarray analysis revealed significant changes in the human PMN transcriptome following exposure to PVL, including up-regulation of molecules that regulate the inflammatory re- sponse. Consistent with the microarray data, mediators of the inflammatory response were released from PMNs after stimulation with PVL. We conclude that exposure of human PMNs to sublytic concentrations of PVL elicits a proinflammatory response that is regulated in part at the level of gene expression. We propose that PVL-mediated priming of PMNs enhances the host innate immune response. J. Leukoc. Biol. 92: 361-374; 2012.
C1 [Graves, Shawna F.; Kobayashi, Scott D.; Braughton, Kevin R.; Whitney, Adeline R.; Rasmussen, Devon L.; DeLeo, Frank R.] NIAID, Lab Bacterial Pathogenesis, NIH, Hamilton, MT USA.
[Sturdevant, Daniel E.] NIAID, Genom Unit, Res Technol Branch, Rocky Mt Labs,NIH, Hamilton, MT 59840 USA.
[Graves, Shawna F.] Univ Montana, Div Biol Sci, Dept Biochem & Biophys, Missoula, MT 59812 USA.
[Kirpotina, Liliya N.; Quinn, Mark T.] Montana State Univ, Dept Immunol & Infect Dis, Bozeman, MT 59717 USA.
RP DeLeo, FR (reprint author), NIAID, Lab Human Bacterial Pathogenesis, Rocky Mt Labs, NIH, 903 S 4th St, Hamilton, MT 59840 USA.
EM fdeleo@niaid.nih.gov
OI DeLeo, Frank/0000-0003-3150-2516
FU NIAID; U.S. National Institutes of Health [RR 020185, GM 103500]
FX This research was supported by the Intramural Research Program of the
NIAID, U.S. National Institutes of Health, and by U.S. National
Institutes of Health grants RR 020185 and GM 103500 (M.T.Q.).
NR 52
TC 23
Z9 23
U1 0
U2 1
PU FEDERATION AMER SOC EXP BIOL
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA
SN 0741-5400
J9 J LEUKOCYTE BIOL
JI J. Leukoc. Biol.
PD AUG
PY 2012
VL 92
IS 2
BP 361
EP 374
DI 10.1189/jlb.1111575
PG 14
WC Cell Biology; Hematology; Immunology
SC Cell Biology; Hematology; Immunology
GA 983MJ
UT WOS:000307123100015
PM 22581932
ER
PT J
AU Alpert, MD
Harvey, JD
Lauer, WA
Reeves, RK
Piatak, M
Carville, A
Mansfield, KG
Lifson, JD
Li, WJ
Desrosiers, RC
Johnson, RP
Evans, DT
AF Alpert, Michael D.
Harvey, Jackson D.
Lauer, W. Anderson
Reeves, R. Keith
Piatak, Michael, Jr.
Carville, Angela
Mansfield, Keith G.
Lifson, Jeffrey D.
Li, Wenjun
Desrosiers, Ronald C.
Johnson, R. Paul
Evans, David T.
TI ADCC Develops Over Time during Persistent Infection with Live-Attenuated
SIV and Is Associated with Complete Protection against SIV(mac)251
Challenge
SO PLOS PATHOGENS
LA English
DT Article
ID SIMIAN IMMUNODEFICIENCY VIRUS; DEPENDENT CELLULAR CYTOTOXICITY;
T-LYMPHOCYTE RESPONSES; RHESUS MACAQUES; VAGINAL CHALLENGE; ANTIBODY
PROTECTION; VACCINE PROTECTION; IMMUNE-RESPONSES; ADULT MACAQUES; HIV
TYPE-1
AB Live-attenuated strains of simian immunodeficiency virus (SIV) routinely confer apparent sterilizing immunity against pathogenic SIV challenge in rhesus macaques. Understanding the mechanisms of protection by live-attenuated SIV may provide important insights into the immune responses needed for protection against HIV-1. Here we investigated the development of antibodies that are functional against neutralization-resistant SIV challenge strains, and tested the hypothesis that these antibodies are associated with protection. In the absence of detectable neutralizing antibodies, Env-specific antibody-dependent cell-mediated cytotoxicity (ADCC) emerged by three weeks after inoculation with SIV Delta nef, increased progressively over time, and was proportional to SIVDnef replication. Persistent infection with SIV Delta nef elicited significantly higher ADCC titers than immunization with a non-persistent SIV strain that is limited to a single cycle of infection. ADCC titers were higher against viruses matched to the vaccine strain in Env, but were measurable against viruses expressing heterologous Env proteins. In two separate experiments, which took advantage of either the strain-specificity or the time-dependent maturation of immunity to overcome complete protection against SIV(mac)251 challenge, measures of ADCC activity were higher among the SIV Delta nef-inoculated macaques that remained uninfected than among those that became infected. These observations show that features of the antibody response elicited by SIV Delta nef are consistent with hallmarks of protection by live-attenuated SIV, and reveal an association between Env-specific antibodies that direct ADCC and apparent sterilizing protection by SIV Delta nef.
C1 [Alpert, Michael D.; Harvey, Jackson D.; Lauer, W. Anderson; Desrosiers, Ronald C.; Evans, David T.] Harvard Univ, Sch Med, New England Primate Res Ctr, Dept Microbiol & Immunobiol, Southborough, MA 01772 USA.
[Reeves, R. Keith; Johnson, R. Paul] Harvard Univ, Sch Med, New England Primate Res Ctr, Div Immunol, Southborough, MA 01772 USA.
[Piatak, Michael, Jr.; Lifson, Jeffrey D.] NCI, SAIC Frederick, Frederick, MD 21701 USA.
[Carville, Angela; Mansfield, Keith G.] Harvard Univ, Sch Med, New England Primate Res Ctr, Dept Pathol, Southborough, MA 01772 USA.
[Li, Wenjun] Univ Massachusetts, Sch Med, Worcester, MA USA.
[Johnson, R. Paul] Massachusetts Gen Hosp, Ragon Inst, Boston, MA 02114 USA.
[Johnson, R. Paul] Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA.
RP Alpert, MD (reprint author), Harvard Univ, Sch Med, New England Primate Res Ctr, Dept Microbiol & Immunobiol, Southborough, MA 01772 USA.
EM david_evans@hms.harvard.edu
RI Li, Wenjun/F-5634-2015
OI Li, Wenjun/0000-0001-5335-7386
FU National Institutes of Health [AI071306, AI063993, RR000168/OD01103];
American Recovery and Reinvestment Act (ARRA) [3P01AI071306-04S1];
National Cancer Institute, National Institutes of Health
[HHSN261200800001E]
FX This work was supported by grants AI071306, AI063993, and
RR000168/OD01103 from the National Institutes of Health, and supplement
3P01AI071306-04S1 from the American Recovery and Reinvestment Act (ARRA)
of 2009, and in part with federal funds from the National Cancer
Institute, National Institutes of Health, under contract
HHSN261200800001E. DTE is an Elizabeth Glaser Scientist of the Elizabeth
Glaser Pediatric AIDS Foundation. The funders had no role in study
design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 69
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U1 0
U2 6
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7374
J9 PLOS PATHOG
JI PLoS Pathog.
PD AUG
PY 2012
VL 8
IS 8
AR e1002890
DI 10.1371/journal.ppat.1002890
PG 12
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA 002TI
UT WOS:000308558000060
PM 22927823
ER
PT J
AU Groseth, A
Marzi, A
Hoenen, T
Herwig, A
Gardner, D
Becker, S
Ebihara, H
Feldmann, H
AF Groseth, Allison
Marzi, Andrea
Hoenen, Thomas
Herwig, Astrid
Gardner, Don
Becker, Stephan
Ebihara, Hideki
Feldmann, Heinz
TI The Ebola Virus Glycoprotein Contributes to but Is Not Sufficient for
Virulence In Vivo
SO PLOS PATHOGENS
LA English
DT Article
ID SUBTYPE RESTON VIRUS; HEMORRHAGIC-FEVER; MOUSE MODEL; FILOVIRUS
INFECTION; NONHUMAN-PRIMATES; ZAIRE-EBOLAVIRUS; MARBURG VIRUSES;
CELLULAR ENTRY; GUINEA-PIGS; PHILIPPINES
AB Among the Ebola viruses most species cause severe hemorrhagic fever in humans; however, Reston ebolavirus (REBOV) has not been associated with human disease despite numerous documented infections. While the molecular basis for this difference remains unclear, in vitro evidence has suggested a role for the glycoprotein (GP) as a major filovirus pathogenicity factor, but direct evidence for such a role in the context of virus infection has been notably lacking. In order to assess the role of GP in EBOV virulence, we have developed a novel reverse genetics system for REBOV, which we report here. Together with a previously published full-length clone for Zaire ebolavirus (ZEBOV), this provides a unique possibility to directly investigate the role of an entire filovirus protein in pathogenesis. To this end we have generated recombinant ZEBOV (rZEBOV) and REBOV (rREBOV), as well as chimeric viruses in which the glycoproteins from these two virus species have been exchanged (rZEBOV-RGP and rREBOV-ZGP). All of these viruses could be rescued and the chimeras replicated with kinetics similar to their parent virus in tissue culture, indicating that the exchange of GP in these chimeric viruses is well tolerated. However, in a mouse model of infection rZEBOV-RGP demonstrated markedly decreased lethality and prolonged time to death when compared to rZEBOV, confirming that GP does indeed contribute to the full expression of virulence by ZEBOV. In contrast, rREBOV-ZGP did not show any signs of virulence, and was in fact slightly attenuated compared to rREBOV, demonstrating that GP alone is not sufficient to confer a lethal phenotype or exacerbate disease in this model. Thus, while these findings provide direct evidence that GP contributes to filovirus virulence in vivo, they also clearly indicate that other factors are needed for the acquisition of full virulence.
C1 [Groseth, Allison; Marzi, Andrea; Hoenen, Thomas; Ebihara, Hideki; Feldmann, Heinz] NIAID, Virol Lab, Div Intramural Res, NIH, Hamilton, MT USA.
[Groseth, Allison; Hoenen, Thomas; Herwig, Astrid; Becker, Stephan] Univ Marburg, Inst Virol, D-3550 Marburg, Germany.
[Groseth, Allison; Marzi, Andrea; Hoenen, Thomas; Ebihara, Hideki; Feldmann, Heinz] Publ Hlth Agcy Canada, Natl Microbiol Lab, Special Pathogens Program, Winnipeg, MB, Canada.
[Groseth, Allison; Feldmann, Heinz] Univ Manitoba, Dept Med Microbiol, Winnipeg, MB, Canada.
[Gardner, Don] NIAID, Rocky Mt Vet Branch, Div Intramural Res, NIH, Hamilton, MT USA.
RP Groseth, A (reprint author), NIAID, Virol Lab, Div Intramural Res, NIH, Hamilton, MT USA.
EM feldmannh@niaid.nih.gov
RI Becker, Stephan/A-1065-2010;
OI Becker, Stephan/0000-0002-2794-5659; Hoenen, Thomas/0000-0002-5829-6305
FU Canadian Institutes of Health Research [MOP - 43921]; European Community
[ERBIC 18 CT9803832]; Natural Sciences and Engineering Research council
of Canada; Canadian Institutes of Health Research; Schering Foundation;
Intramural Research Program of the NIH; NIAID; Public Health Agency of
Canada; Philipps Universitat Marburg
FX This work was supported in part by grants of the Canadian Institutes of
Health Research (MOP - 43921; http://www.cihr-irsc.gc.ca) and the
European Community (INCO-grant ERBIC 18 CT9803832; http://europa.eu/) as
well as fellowships from the Natural Sciences and Engineering Research
council of Canada (A. G., A. M., T. H.; http://www.nserc-crsng.gc.ca),
the Canadian Institutes of Health Research (AG and TH;
http://www.cihr-irsc.gc.ca) and the Schering Foundation (TH;
http://www.scheringstiftung.de/en.html). This research was also
supported in part by the Intramural Research Program of the NIH, NIAID,
the Public Health Agency of Canada and the Philipps Universitat Marburg.
The funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript. Opinions,
interpretations, conclusions, and recommendations are those of the
authors and are not necessarily endorsed by the National Institutes of
Health, Public Health Agency of Canada or the Philipps Universitat
Marburg.
NR 55
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U1 0
U2 24
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7374
J9 PLOS PATHOG
JI PLoS Pathog.
PD AUG
PY 2012
VL 8
IS 8
AR e1002847
DI 10.1371/journal.ppat.1002847
PG 12
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA 002TI
UT WOS:000308558000025
PM 22876185
ER
PT J
AU Lionakis, MS
Fischer, BG
Lim, JK
Swamydas, M
Wan, WZ
Lee, CCR
Cohen, JI
Scheinberg, P
Gao, JL
Murphy, PM
AF Lionakis, Michail S.
Fischer, Brett G.
Lim, Jean K.
Swamydas, Muthulekha
Wan, Wuzhou
Lee, Chyi-Chia Richard
Cohen, Jeffrey I.
Scheinberg, Phillip
Gao, Ji-Liang
Murphy, Philip M.
TI Chemokine Receptor Ccr1 Drives Neutrophil-Mediated Kidney
Immunopathology and Mortality in Invasive Candidiasis
SO PLOS PATHOGENS
LA English
DT Article
ID MACROPHAGE-INFLAMMATORY PROTEIN-1-ALPHA; CHRONIC GRANULOMATOUS-DISEASE;
SYSTEMIC CANDIDIASIS; HOST-DEFENSE; INCREASED SUSCEPTIBILITY; ALBICANS
INFECTION; INJURY MOLECULE-1; RENAL FIBROSIS; TH1 RESPONSES; KNOCKOUT
MICE
AB Invasive candidiasis is the 4th leading cause of nosocomial bloodstream infection in the US with mortality that exceeds 40% despite administration of antifungal therapy; neutropenia is a major risk factor for poor outcome after invasive candidiasis. In a fatal mouse model of invasive candidiasis that mimics human bloodstream-derived invasive candidiasis, the most highly infected organ is the kidney and neutrophils are the major cellular mediators of host defense; however, factors regulating neutrophil recruitment have not been previously defined. Here we show that mice lacking chemokine receptor Ccr1, which is widely expressed on leukocytes, had selectively impaired accumulation of neutrophils in the kidney limited to the late phase of the time course of the model; surprisingly, this was associated with improved renal function and survival without affecting tissue fungal burden. Consistent with this, neutrophils from wild-type mice in blood and kidney switched from Ccr1(lo) to Ccr1(high) at late time-points post-infection, when Ccr1 ligands were produced at high levels in the kidney and were chemotactic for kidney neutrophils ex vivo. Further, when a 1:1 mixture of Ccr1(+/+) and Ccr1(-/-) donor neutrophils was adoptively transferred intravenously into Candida-infected Ccr1(+/+) recipient mice, neutrophil trafficking into the kidney was significantly skewed toward Ccr1(+/+) cells. Thus, neutrophil Ccr1 amplifies late renal immunopathology and increases mortality in invasive candidiasis by mediating excessive recruitment of neutrophils from the blood to the target organ.
C1 [Lionakis, Michail S.; Fischer, Brett G.; Swamydas, Muthulekha] NIAID, Clin Mycol Unit, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA.
[Lionakis, Michail S.; Fischer, Brett G.; Lim, Jean K.; Swamydas, Muthulekha; Wan, Wuzhou; Gao, Ji-Liang; Murphy, Philip M.] NIAID, Mol Signaling Sect, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA.
[Lee, Chyi-Chia Richard] NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Cohen, Jeffrey I.] NIAID, Med Virol Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
[Scheinberg, Phillip] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA.
RP Lionakis, MS (reprint author), NIAID, Clin Mycol Unit, Lab Mol Immunol, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM lionakism@mail.nih.gov; pmm@nih.gov
RI Wan, Wuhzou/H-8556-2013; Lee, Chyi-Chia/I-1938-2013;
OI Lee, Chyi-Chia/0000-0002-5306-7781; Scheinberg,
Phillip/0000-0002-9047-4538
FU Division of Intramural Research of the National Institute of Allergy and
Infectious Diseases, National Institutes of Health, USA
FX This work was supported by the Division of Intramural Research of the
National Institute of Allergy and Infectious Diseases, National
Institutes of Health, USA. The funding source had no role in study
design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 54
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PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7374
J9 PLOS PATHOG
JI PLoS Pathog.
PD AUG
PY 2012
VL 8
IS 8
AR e1002865
DI 10.1371/journal.ppat.1002865
PG 18
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA 002TI
UT WOS:000308558000042
PM 22916017
ER
PT J
AU Morin, TJ
Broering, TJ
Leav, BA
Blair, BM
Rowley, KJ
Boucher, EN
Wang, Y
Cheslock, PS
Knauber, M
Olsen, DB
Ludmerer, SW
Szabo, G
Finberg, RW
Purcell, RH
Lanford, RE
Ambrosino, DM
Molrine, DC
Babcock, GJ
AF Morin, Trevor J.
Broering, Teresa J.
Leav, Brett A.
Blair, Barbra M.
Rowley, Kirk J.
Boucher, Elisabeth N.
Wang, Yang
Cheslock, Peter S.
Knauber, Michael
Olsen, David B.
Ludmerer, Steve W.
Szabo, Gyongyi
Finberg, Robert W.
Purcell, Robert H.
Lanford, Robert E.
Ambrosino, Donna M.
Molrine, Deborah C.
Babcock, Gregory J.
TI Human Monoclonal Antibody HCV1 Effectively Prevents and Treats HCV
Infection in Chimpanzees
SO PLOS PATHOGENS
LA English
DT Article
ID HEPATITIS-C-VIRUS; ORTHOTOPIC LIVER-TRANSPLANTATION; B TYPE-I;
NEUTRALIZING ANTIBODIES; NATURAL-HISTORY; ANTIVIRAL THERAPY; IMMUNE
GLOBULIN; CELL-CULTURE; NON-A; ENTRY
AB Hepatitis C virus (HCV) infection is a leading cause of liver transplantation and there is an urgent need to develop therapies to reduce rates of HCV infection of transplanted livers. Approved therapeutics for HCV are poorly tolerated and are of limited efficacy in this patient population. Human monoclonal antibody HCV1 recognizes a highly-conserved linear epitope of the HCV E2 envelope glycoprotein (amino acids 412-423) and neutralizes a broad range of HCV genotypes. In a chimpanzee model, a single dose of 250 mg/kg HCV1 delivered 30 minutes prior to infusion with genotype 1a H77 HCV provided complete protection from HCV infection, whereas a dose of 50 mg/kg HCV1 did not protect. In addition, an acutely-infected chimpanzee given 250 mg/kg HCV1 42 days following exposure to virus had a rapid reduction in viral load to below the limit of detection before rebounding 14 days later. The emergent virus displayed an E2 mutation (N415K/D) conferring resistance to HCV1 neutralization. Finally, three chronically HCV-infected chimpanzees were treated with a single dose of 40 mg/kg HCV1 and viral load was reduced to below the limit of detection for 21 days in one chimpanzee with rebounding virus displaying a resistance mutation (N417S). The other two chimpanzees had 0.5-1.0 log(10) reductions in viral load without evidence of viral resistance to HCV1. In vitro testing using HCV pseudovirus (HCVpp) demonstrated that the sera from the poorly-responding chimpanzees inhibited the ability of HCV1 to neutralize HCVpp. Measurement of antibody responses in the chronically-infected chimpanzees implicated endogenous antibody to E2 and interference with HCV1 neutralization although other factors may also be responsible. These data suggest that human monoclonal antibody HCV1 may be an effective therapeutic for the prevention of graft infection in HCV-infected patients undergoing liver transplantation.
C1 [Morin, Trevor J.; Broering, Teresa J.; Leav, Brett A.; Blair, Barbra M.; Rowley, Kirk J.; Boucher, Elisabeth N.; Wang, Yang; Cheslock, Peter S.; Knauber, Michael; Ambrosino, Donna M.; Molrine, Deborah C.; Babcock, Gregory J.] Univ Massachusetts, Sch Med, Boston, MA 02125 USA.
[Olsen, David B.; Ludmerer, Steve W.] Merck Res Labs, West Point, PA USA.
[Szabo, Gyongyi; Finberg, Robert W.] Univ Massachusetts, Sch Med, Dept Med, Worcester, MA USA.
[Purcell, Robert H.] NIH, Bethesda, MD 20892 USA.
[Lanford, Robert E.] Texas Biomed Res Inst, Dept Virol & Immunol, San Antonio, TX USA.
[Lanford, Robert E.] SW Natl Primate Res Ctr, San Antonio, TX USA.
RP Morin, TJ (reprint author), Univ Calif Santa Cruz, Dept Biomol Engn, Santa Cruz, CA 95064 USA.
EM greg.babcock@umassmed.edu
FU MassBiologics; Intramural Research Program of the NIAID, NIH; NIH grant
from the National Center for Research Resources [P51 RR013986]; NIH
grant from the Office of Research Infrastructure Programs/Office of the
Director [OD P51 OD011133]; NIH Research Facilities Improvement Program
[C06 RR012087, C06 RR016228]
FX This study was funded by MassBiologics. This research was supported in
part by the Intramural Research Program of the NIAID, NIH. The
chimpanzee studies performed at the Southwest National Primate Research
Center used resources that were supported by NIH grant P51 RR013986 from
the National Center for Research Resources and that are currently
supported by NIH grant OD P51 OD011133 from the Office of Research
Infrastructure Programs/Office of the Director. The investigation used
facilities constructed with support from NIH Research Facilities
Improvement Program grants C06 RR012087 and C06 RR016228. Experiments
were designed and conducted by authors employed by MassBiologics and Dr.
Babcock, an employee of MassBiologics, prepared the first draft of the
manuscript. All authors reviewed the manuscript for accuracy. For in
vitro experimentation, the funders had a role in study design, data
collection and data analysis. For chimpanzee studies, the funders had a
role in study design and data analysis but had no role in study conduct
or data collection.
NR 55
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U1 0
U2 3
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7374
J9 PLOS PATHOG
JI PLoS Pathog.
PD AUG
PY 2012
VL 8
IS 8
AR e1002895
DI 10.1371/journal.ppat.1002895
PG 13
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA 002TI
UT WOS:000308558000062
PM 22952447
ER
PT J
AU Price, AJ
Fletcher, AJ
Schaller, T
Elliott, T
Lee, K
KewalRamani, VN
Chin, JW
Towers, GJ
James, LC
AF Price, Amanda J.
Fletcher, Adam J.
Schaller, Torsten
Elliott, Tom
Lee, KyeongEun
KewalRamani, Vineet N.
Chin, Jason W.
Towers, Greg J.
James, Leo C.
TI CPSF6 Defines a Conserved Capsid Interface that Modulates HIV-1
Replication
SO PLOS PATHOGENS
LA English
DT Article
ID IMMUNODEFICIENCY-VIRUS TYPE-1; FACTOR-I-M; NUCLEAR IMPORT; REVERSE
TRANSCRIPTION; SR PROTEINS; EVOLUTIONARY CONSERVATION; PREINTEGRATION
COMPLEXES; ASSEMBLY INHIBITOR; NONDIVIDING CELLS; INFECTION
AB The HIV-1 genome enters cells inside a shell comprised of capsid (CA) protein. Variation in CA sequence alters HIV-1 infectivity and escape from host restriction factors. However, apart from the Cyclophilin A-binding loop, CA has no known interfaces with which to interact with cellular cofactors. Here we describe a novel protein-protein interface in the N-terminal domain of HIV-1 CA, determined by X-ray crystallography, which mediates both viral restriction and host cofactor dependence. The interface is highly conserved across lentiviruses and is accessible in the context of a hexameric lattice. Mutation of the interface prevents binding to and restriction by CPSF6-358, a truncated cytosolic form of the RNA processing factor, cleavage and polyadenylation specific factor 6 (CPSF6). Furthermore, mutations that prevent CPSF6 binding also relieve dependence on nuclear entry cofactors TNPO3 and RanBP2. These results suggest that the HIV-1 capsid mediates direct host cofactor interactions to facilitate viral infection.
C1 [Price, Amanda J.; Elliott, Tom; Chin, Jason W.; James, Leo C.] MRC, Mol Biol Lab, Div Prot & Nucle Acid Chem, Cambridge CB2 2QH, England.
[Fletcher, Adam J.; Schaller, Torsten; Towers, Greg J.] UCL, MRC, Ctr Med Mol Virol, Div Infect & Immun, London, England.
[Lee, KyeongEun; KewalRamani, Vineet N.] NCI, HIV Drug Resistance Program, Frederick, MD 21701 USA.
RP Price, AJ (reprint author), MRC, Mol Biol Lab, Div Prot & Nucle Acid Chem, Hills Rd, Cambridge CB2 2QH, England.
EM lcj@mrc-lmb.cam.ac.uk
RI Towers, Greg/H-8892-2012;
OI Towers, Gregory/0000-0002-7707-0264; Schaller,
Torsten/0000-0001-9597-4112
FU Medical Research Council [U105181010]; European Research Council [ERC
281627 - IAI]; Wellcome Trust; National Institute for Health Research
UCL/UCLH Comprehensive Biomedical Research Centre; Emmanuel College,
Cambridge; National Cancer Institute's intramural Center for Cancer
Research
FX Funding was provided by: Medical Research Council (U105181010: AJP, AJF,
TS, TE, JWC, GJT, LCJ); European Research Council (ERC 281627 - IAI);
Wellcome Trust; National Institute for Health Research UCL/UCLH
Comprehensive Biomedical Research Centre; Emmanuel College, Cambridge;
National Cancer Institute's intramural Center for Cancer Research. The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 43
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U1 1
U2 6
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7374
J9 PLOS PATHOG
JI PLoS Pathog.
PD AUG
PY 2012
VL 8
IS 8
AR e1002896
DI 10.1371/journal.ppat.1002896
PG 14
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA 002TI
UT WOS:000308558000063
PM 22956906
ER
PT J
AU Rodriguez-Martin, S
Kropp, KA
Wilhelmi, V
Lisnic, VJ
Hsieh, WY
Blanc, M
Livingston, A
Busche, A
Tekotte, H
Messerle, M
Auer, M
Fraser, I
Jonjic, S
Angulo, A
Reddehase, MJ
Ghazal, P
AF Rodriguez-Martin, Sara
Kropp, Kai Alexander
Wilhelmi, Vanessa
Lisnic, Vanda Juranic
Hsieh, Wei Yuan
Blanc, Mathieu
Livingston, Andrew
Busche, Andreas
Tekotte, Hille
Messerle, Martin
Auer, Manfred
Fraser, Iain
Jonjic, Stipan
Angulo, Ana
Reddehase, Matthias J.
Ghazal, Peter
TI Ablation of the Regulatory IE1 Protein of Murine Cytomegalovirus Alters
In Vivo Pro-inflammatory TNF-alpha Production during Acute Infection
SO PLOS PATHOGENS
LA English
DT Article
ID TUMOR-NECROSIS-FACTOR; IMMEDIATE-EARLY PROTEIN;
PROMYELOCYTIC-LEUKEMIA-PROTEIN; GENE-EXPRESSION; MOUSE CYTOMEGALOVIRUS;
SIGNAL-TRANSDUCTION; PRIMARY MACROPHAGES; CYTOKINE INDUCTION; VIRAL
PATHOGENESIS; ESCHERICHIA-COLI
AB Little is known about the role of viral genes in modulating host cytokine responses. Here we report a new functional role of the viral encoded IE1 protein of the murine cytomegalovirus in sculpting the inflammatory response in an acute infection. In time course experiments of infected primary macrophages (M Phi s) measuring cytokine production levels, genetic ablation of the immediate-early 1 (ie1) gene results in a significant increase in TNF alpha production. Intracellular staining for cytokine production and viral early gene expression shows that TNF alpha production is highly associated with the productively infected M Phi population of cells. The ie1- dependent phenotype of enhanced MW TNF alpha production occurs at both protein and RNA levels. Noticeably, we show in a series of in vivo infection experiments that in multiple organs the presence of ie1 potently inhibits the pro-inflammatory cytokine response. From these experiments, levels of TNF alpha, and to a lesser extent IFN beta, but not the anti-inflammatory cytokine IL10, are moderated in the presence of ie1. The ie1- mediated inhibition of TNF alpha production has a similar quantitative phenotype profile in infection of susceptible (BALB/c) and resistant (C57BL/6) mouse strains as well as in a severe immuno-ablative model of infection. In vitro experiments with infected macrophages reveal that deletion of ie1 results in increased sensitivity of viral replication to TNF alpha inhibition. However, in vivo infection studies show that genetic ablation of TNF alpha or TNFRp55 receptor is not sufficient to rescue the restricted replication phenotype of the ie1 mutant virus. These results provide, for the first time, evidence for a role of IE1 as a regulator of the pro-inflammatory response and demonstrate a specific pathogen gene capable of moderating the host production of TNF alpha in vivo.
C1 [Rodriguez-Martin, Sara; Kropp, Kai Alexander; Hsieh, Wei Yuan; Blanc, Mathieu; Livingston, Andrew; Ghazal, Peter] Univ Edinburgh, Div Pathway Med, Edinburgh, Midlothian, Scotland.
[Rodriguez-Martin, Sara; Kropp, Kai Alexander; Hsieh, Wei Yuan; Blanc, Mathieu; Livingston, Andrew; Ghazal, Peter] Univ Edinburgh, Ctr Infect Dis, Edinburgh, Midlothian, Scotland.
[Wilhelmi, Vanessa; Reddehase, Matthias J.] Johannes Gutenberg Univ Mainz, Univ Med Ctr, Inst Virol, Mainz, Germany.
[Lisnic, Vanda Juranic; Jonjic, Stipan] Univ Rijeka, Dept Histol & Embryol, Ctr Prote, Fac Med, Rijeka, Croatia.
[Busche, Andreas; Messerle, Martin] Hannover Med Sch, Dept Virol, D-3000 Hannover, Germany.
[Tekotte, Hille] Univ Edinburgh, Wellcome Trust Ctr Cell Biol, Edinburgh, Midlothian, Scotland.
[Auer, Manfred] Univ Edinburgh, Sch Biol Sci CSE, Edinburgh, Midlothian, Scotland.
[Auer, Manfred] Sch Biomed Sci CMVM, Edinburgh, Midlothian, Scotland.
[Fraser, Iain] NIAID, Lab Syst Biol, NIH, Bethesda, MD 20892 USA.
[Angulo, Ana] Inst Invest Biomed August Pi & Sunyer, Barcelona, Spain.
RP Rodriguez-Martin, S (reprint author), Univ Edinburgh, Div Pathway Med, Edinburgh, Midlothian, Scotland.
EM p.ghazal@ed.ac.uk
RI Jonjic, Stipan/C-5657-2016;
OI Kropp, Kai Alexander/0000-0001-8505-3440; Messerle,
Martin/0000-0002-1227-3933
FU Wellcome Trust [WT066784/Z/02/Z]; BBSRC/EPSRC; Centre for Integrative
Systems Biology (CISB) [BB/D019621/1]; Deutsche Forschungsgemeinschaft
[KR-3890/1-1, SFB 587, SFB 490]; University of Edinburgh Principal's
Fellowship; Wellcome Trust; European Research Council [233457-SCG];
Ministerio de Ciencia e Innovacion [SAF2008-00382, SAF2011-25155];
National Institutes of Health
FX This work was supported by: The Wellcome Trust (WT066784/Z/02/Z), and
the BBSRC/EPSRC to SynthSys, a Centre for Integrative Systems Biology
(CISB) reference BB/D019621/1 to PG. Deutsche Forschungsgemeinschaft,
research fellowship KR-3890/1-1 to KK. BBSRC studentship, and University
of Edinburgh Principal's Fellowship to SRM. The work of HT was supported
by grants from the Wellcome Trust and the European Research Council
(233457-SCG) to Mike Tyers. Deutsche Forschungsgemeinschaft, SFB 587,
individual project A13 to MM. Deutsche Forschungsgemeinschaft, SFB 490,
individual projects E2 and E4 to VW and MJR. Ministerio de Ciencia e
Innovacion (SAF2008-00382 and SAF2011-25155) to AA. SULSA (Scottish
Universities Life Sciences Alliance) to MA. Helmholtz Society through
collaborative research program VISTRIE to SJ. British Heart Foundation
reference FS/05/022 and University of Edinburgh Alumni Fund to MB. IF is
funded by 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 77
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U1 0
U2 4
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7374
J9 PLOS PATHOG
JI PLoS Pathog.
PD AUG
PY 2012
VL 8
IS 8
AR e1002901
DI 10.1371/journal.ppat.1002901
PG 18
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA 002TI
UT WOS:000308558000067
PM 22952450
ER
PT J
AU Riley, WT
Stevens, VJ
Zhu, SH
Morgan, G
Grossman, D
AF Riley, William T.
Stevens, Victor J.
Zhu, Shu-Hong
Morgan, Glen
Grossman, Debra
TI Overview of the consortium of hospitals advancing research on tobacco
(chart)
SO TRIALS
LA English
DT Editorial Material
DE Hospitals; Smoking cessation; Tobacco control
ID SMOKING-CESSATION; ABSTINENCE; TRIALS
AB Background: The Consortium of Hospitals Advancing Research on Tobacco (CHART) is a network of six projects and a research coordinating unit funded by the National Heart, Lung, and Blood Institute, the National Cancer Institute, the National Institute on Drug Abuse, and the National Institutes of Health (NIH) Office of Behavioral and Social Science Research. The CHART projects will assess the effectiveness and cost-effectiveness of smoking cessation interventions initiated during hospitalization and continued post-discharge.
Methods/design: Along with a seventh project funded previously under the NIH Challenge grants, the CHART projects will assess smoking cessation strategies delivered to approximately 10,000 hospitalized smokers across a geographically diverse group of nearly 20 private, public, academic, and community hospitals. The CHART research coordinating unit at Kaiser Permanente Center for Health Research provides organizational and data coordination support, facilitating the development of common measures for combining data from multiple CHART projects.
Discussion: The targeted enrollment in CHART, if achieved, will represent the largest, most diverse pooled dataset of hospitalized smokers receiving smoking cessation assistance, and is designed to contribute to the dissemination and implementation of smoking cessation interventions provided by hospital systems.
C1 [Riley, William T.] NHLBI, Bethesda, MD 20892 USA.
[Stevens, Victor J.] Kaiser Permanente Ctr Hlth Res, Portland, OR USA.
[Zhu, Shu-Hong] Univ Calif San Diego, San Diego, CA 92103 USA.
[Morgan, Glen] NCI, Bethesda, MD 20892 USA.
[Grossman, Debra] NIDA, Bethesda, MD 20892 USA.
RP Riley, WT (reprint author), NHLBI, 6701 Rockledge Dr,MSC 7936, Bethesda, MD 20892 USA.
EM wiriley@mail.nih.gov
FU NCI NIH HHS [U01CA159533]; NHLBI NIH HHS [RC1HL099668, U01HL105218,
U01HL105232, U01HL52333, U01HL105231, U01HL105229]; NIDA NIH HHS
[U01DA031515]
NR 14
TC 15
Z9 15
U1 0
U2 4
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 1
PY 2012
VL 13
AR 122
DI 10.1186/1745-6215-13-122
PG 8
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 025QA
UT WOS:000310205500001
PM 22852768
ER
PT J
AU Bhatnagar, P
Lu, XC
Evans, MK
LaVeist, TA
Zonderman, AB
Carter, DL
Arking, DE
Fletcher, CA
AF Bhatnagar, Pallav
Lu, Xiaochun
Evans, Michele K.
LaVeist, Thomas A.
Zonderman, Alan B.
Carter, Darryl L.
Arking, Dan E.
Fletcher, Craig A.
TI Genetic Variants in Platelet Factor 4 Modulate Inflammatory and Platelet
Activation Biomarkers
SO CIRCULATION-CARDIOVASCULAR GENETICS
LA English
DT Article
DE association study; atherosclerosis; inflammation; platelets; chemokines;
PF4; TNF-alpha
ID CORONARY-ARTERY-DISEASE; CHEMOKINE RECEPTOR CX3CR1; ATHEROSCLEROTIC
LESIONS; REDUCES ATHEROSCLEROSIS; CARDIOVASCULAR-DISEASE;
MYOCARDIAL-INFARCTION; SOCIOECONOMIC-STATUS; APOE(-/-) MICE; DEFICIENT
MICE; FACTOR-I
AB Background-African Americans suffer from higher prevalence and severity of atherosclerosis compared with whites, highlighting racial and ethnic disparities in cardiovascular disease. Previous studies have pointed to the role of vascular inflammation and platelet activation in the formation of atherosclerotic lesions.
Methods and Results-We explored the role of genetic variation in 4 chemokine/chemokine receptor genes (CX3CR1, CX3CL1, CXCR3, and PF4) on systemic inflammation and platelet activation serum biomarkers (fractalkine, platelet P-selectin, platelet factor 4 [PF4], and tumor necrosis factor-alpha). In total, 110 single nucleotide polymorphisms were tested among 1042 African Americans and 763 whites. The strongest association with serum PF4 levels was observed for rs168449, which was significant in both racial groups (P value: African Americans=0.0017, whites=0.014, combined=1.2x10(-4)), and remained significant after permutation-based multiple corrections (P-c value: combined=0.0013). After accounting for the effect of rs168449, we identified another significant single nucleotide polymorphism (rs1435520), suggesting a second independent signal regulating serum PF4 levels (conditional P value: African Americans=0.02, whites=0.02). Together, these single nucleotide polymorphisms explained 0.98% and 1.23% of serum PF4 variance in African Americans and whites, respectively. Additionally, in African Americans, we found an additional PF4 variant (rs8180167), uncorrelated with rs168449 and rs1435520, associated with serum tumor necrosis factor-alpha levels (P=0.008, P-c=0.048).
Conclusions-Our study highlights the importance of PF4 variants in the regulation of platelet activation (PF4) and systemic inflammation (tumor necrosis factor-alpha) serum biomarkers. (Circ Cardiovasc Genet. 2012;5:412-421.)
C1 [Bhatnagar, Pallav; Arking, Dan E.] Johns Hopkins Univ, McKusick Nathans Inst Genet Med, Sch Med, Baltimore, MD 21205 USA.
[Lu, Xiaochun; Fletcher, Craig A.] Univ N Carolina, Chapel Hill Sch Med, Dept Pathol & Lab Med, Chapel Hill, NC 27515 USA.
[Evans, Michele K.; Zonderman, Alan B.] NIA, Clin Res Branch, Intramural Res Program, Hlth Dispar Res Sect, Baltimore, MD 21224 USA.
[LaVeist, Thomas A.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Hlth Policy & Management, Baltimore, MD USA.
[Carter, Darryl L.] Nora Therapeut Inc, Palo Alto, CA USA.
RP Arking, DE (reprint author), Johns Hopkins Univ, McKusick Nathans Inst Genet Med, Sch Med, 733 N Broadway,Room 447, Baltimore, MD 21205 USA.
EM arking@jhmi.edu; craig_fletcher@med.unc.edu
RI Bhatnagar, Pallav/A-1280-2013
FU National Center for Research Resources (NCRR) [1UL1RR025005]; National
Institutes of Health (NIH); NIH Roadmap for Medical Research; Intramural
Research Program of the NIH; National Institute on Aging
FX This publication was made possible by Grant No. 1UL1RR025005 from the
National Center for Research Resources (NCRR), a component of the
National Institutes of Health (NIH), and the NIH Roadmap for Medical
Research. This research was supported in part by the Intramural Research
Program of the NIH, National Institute on Aging. Its contents are solely
the responsibility of the authors and do not necessarily represent the
official view of NCRR or NIH. Information on NCRR is available at
http://www.ncrr.nih.gov/. Information on Re-engineering the Clinical
Research Enterprise can be obtained from
http://nihroadmap.nih.gov/clinicalresearch/overview-translational.asp.
NR 45
TC 2
Z9 3
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1942-325X
J9 CIRC-CARDIOVASC GENE
JI Circ.-Cardiovasc. Genet.
PD AUG
PY 2012
VL 5
IS 4
BP 412
EP 421
DI 10.1161/CIRCGENETICS.111.961813
PG 10
WC Cardiac & Cardiovascular Systems; Genetics & Heredity
SC Cardiovascular System & Cardiology; Genetics & Heredity
GA 021LD
UT WOS:000309885400006
PM 22763266
ER
PT J
AU Gandjbakhche, A
Kainerstorfer, JM
Tromberg, B
AF Gandjbakhche, Amir
Kainerstorfer, Jana M.
Tromberg, Bruce
TI Optical Diagnostic and Biophotonic Methods from Bench to Bedside
SO JOURNAL OF BIOMEDICAL OPTICS
LA English
DT Editorial Material
C1 [Gandjbakhche, Amir] NIH, Bethesda, MD 20892 USA.
[Kainerstorfer, Jana M.] Tufts Univ, Medford, MA 02155 USA.
RP Gandjbakhche, A (reprint author), NIH, Bethesda, MD 20892 USA.
NR 1
TC 0
Z9 0
U1 0
U2 3
PU SPIE-SOC PHOTO-OPTICAL INSTRUMENTATION ENGINEERS
PI BELLINGHAM
PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA
SN 1083-3668
J9 J BIOMED OPT
JI J. Biomed. Opt.
PD AUG
PY 2012
VL 17
IS 8
AR 081401
PG 1
WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine &
Medical Imaging
SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine &
Medical Imaging
GA 018WF
UT WOS:000309696800011
PM 23224162
ER
PT J
AU Kopp, JB
AF Kopp, Jeffrey B.
TI Glomerular Homeostasis Requires a Match between Podocyte Mass and
Metabolic Load
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Editorial Material
ID CHRONIC KIDNEY-DISEASE; GLOMERULOSCLEROSIS; PROGRESSION; OBESITY
C1 NIDDKD, Kidney Dis Sect, NIH, Bethesda, MD 20892 USA.
RP Kopp, JB (reprint author), NIDDKD, Kidney Dis Sect, NIH, 10 Ctr Dr, Bethesda, MD 20892 USA.
EM Jbkopp@nih.gov
OI Kopp, Jeffrey/0000-0001-9052-186X
FU Intramural NIH HHS
NR 14
TC 3
Z9 4
U1 0
U2 3
PU AMER SOC NEPHROLOGY
PI WASHINGTON
PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA
SN 1046-6673
J9 J AM SOC NEPHROL
JI J. Am. Soc. Nephrol.
PD AUG
PY 2012
VL 23
IS 8
BP 1273
EP 1275
DI 10.1681/ASN.2012060618
PG 3
WC Urology & Nephrology
SC Urology & Nephrology
GA 020BL
UT WOS:000309783500001
PM 22797185
ER
PT J
AU Troendle, JF
Yu, KF
Westfall, PH
Pennello, G
Schisterman, EF
AF Troendle, James F.
Yu, Kai F.
Westfall, Peter H.
Pennello, Gene
Schisterman, Enrique F.
TI Comparing the Expected Misclassification Cost for Two Classifiers Based
on Estimates From the Same Sample
SO STATISTICS IN BIOPHARMACEUTICAL RESEARCH
LA English
DT Article
DE Likelihood ratio test; Multinomial; Power; Type I error; Wald-type test
ID DIAGNOSTIC-TESTS; PREDICTION; VALUES; RISK
AB In this article, we consider the problem of comparing two binary classifiers evaluated on the same sample. McNemar's test can be used to compare overall predictive accuracy. However, to evaluate the classifiers in a clinically relevant manner, expected misclassification cost should be accounted for. We show that a Wald-type test can be constructed for this purpose. We further derive a likelihood ratio test for comparison of two classifiers based on expected misclassification cost. The null distribution of the test statistic is approximated by simulation from strategically chosen parameter values. The properties of the tests are examined through simulation of correlated classification indicators. The Wald-type test has approximate Type I error control while maintaining a power advantage over the likelihood ratio test and is therefore recommended for most applications. If conservative error control is desired, the likelihood ratio test calibrated from several strategically chosen parameter values is recommended. The methods are illustrated on a prospective cohort study of coronary heart disease and also on a case-control study of preeclampsia. An interval of misclassification cost ratios for which the Wald test rejects the null hypothesis of equal expected misclassification cost is reported. Full simulation results are available as supplementary tables (S1-S6) in the online supplementary materials.
C1 [Troendle, James F.] NHLBI, Off Biostat Res, NIH, DHHS, Bethesda, MD 20892 USA.
[Yu, Kai F.] Tsinghua Univ, Dept Math Sci, Beijing 100084, Peoples R China.
[Yu, Kai F.] Tsinghua Univ, Math Sci Ctr, Beijing 100084, Peoples R China.
[Westfall, Peter H.] Texas Tech Univ, Rawls Coll Business, Area Informat Syst & Quantitat Sci ISQS, Lubbock, TX 79409 USA.
[Pennello, Gene] US FDA, Diagnost Devices Branch, Div Biostat, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA.
[Schisterman, Enrique F.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Epidemiol Stat & Prevent Res, NIH,DHHS, Bethesda, MD 20892 USA.
RP Troendle, JF (reprint author), NHLBI, Off Biostat Res, NIH, DHHS, Bldg 10, Bethesda, MD 20892 USA.
EM jt3t@nih.gov; kfyu@math.tsinghua.edu.cn; peter.westfall@ttu.edu;
gene.pennello@fda.hhs.gov; schistee@mail.nih.gov
OI Schisterman, Enrique/0000-0003-3757-641X
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development, National Institutes of Health (NIH)
FX This research was supported in part by the Intramural Research Program
of the Eunice Kennedy Shriver National Institute of Child Health and
Human Development, National Institutes of Health (NIH). This study
utilized the high-performance computational capabilities of the Biowulf
Linux cluster at the NIH, Bethesda, MD (http://biowulf.nih.gov).
NR 24
TC 0
Z9 0
U1 0
U2 3
PU AMER STATISTICAL ASSOC
PI ALEXANDRIA
PA 732 N WASHINGTON ST, ALEXANDRIA, VA 22314-1943 USA
SN 1946-6315
J9 STAT BIOPHARM RES
JI Stat. Biopharm. Res.
PD AUG
PY 2012
VL 4
IS 3
BP 301
EP 312
DI 10.1080/19466315.2012.695263
PG 12
WC Mathematical & Computational Biology; Statistics & Probability
SC Mathematical & Computational Biology; Mathematics
GA 019PC
UT WOS:000309750800009
ER
PT J
AU Nacif, MS
Zavodni, A
Kawel, N
Choi, EY
Lima, JAC
Bluemke, DA
AF Nacif, Marcelo Souto
Zavodni, Anna
Kawel, Nadine
Choi, Eui-Young
Lima, Joao A. C.
Bluemke, David A.
TI Cardiac magnetic resonance imaging and its electrocardiographs (ECG):
tips and tricks
SO INTERNATIONAL JOURNAL OF CARDIOVASCULAR IMAGING
LA English
DT Article
DE Magnetic resonance imaging; ECG; Trigger
ID GATED MRI; CINE MRI; INTERFERENCE; SYSTEM
AB All cardiac magnetic resonance (CMR) techniques aim to create still depictions of a dynamic and ever-adapting organ. Most CMR methods rely on cardiac gating to capture information during fleeting periods of relative cardiac quiescence, at end diastole or end systole, or to acquire partial images throughout the cardiac cycle and average these signals over several heart beats. Since the inception of clinical CMR in the early 1980s, priority has been given to improving methods for image gating. The aim of this work is to provide a basic understanding of the ECG acquisition, demonstrate common ECG-related artifacts and to provide practical methods for overcoming these issues. Meticulous ECG preparation is essential for optimal CMR acquisition and these techniques must be adaptable to the individual patient.
C1 [Nacif, Marcelo Souto; Zavodni, Anna; Kawel, Nadine; Bluemke, David A.] NIH, Ctr Clin, Bethesda, MD 20892 USA.
[Nacif, Marcelo Souto; Choi, Eui-Young; Lima, Joao A. C.] Johns Hopkins Univ, Sch Med, Div Cardiol, Baltimore, MD USA.
[Nacif, Marcelo Souto] Univ Fed Fluminense, Dept Radiol, Niteroi, RJ, Brazil.
[Bluemke, David A.] Natl Inst Biomed Imaging & Bioengn, Bethesda, MD USA.
RP Bluemke, DA (reprint author), NIH, Ctr Clin, 10 Ctr Dr,Bldg 10,Rm 1C355, Bethesda, MD 20892 USA.
EM bluemked@nih.gov
OI Bluemke, David/0000-0002-8323-8086
FU National Institutes of Health (NIH) Intramural program
FX Funded by the National Institutes of Health (NIH) Intramural program.
NR 21
TC 4
Z9 4
U1 0
U2 4
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 1569-5794
J9 INT J CARDIOVAS IMAG
JI Int. J. Cardiovasc. Imaging
PD AUG
PY 2012
VL 28
IS 6
BP 1465
EP 1475
DI 10.1007/s10554-011-9957-4
PG 11
WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical
Imaging
SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine &
Medical Imaging
GA 016VH
UT WOS:000309547300022
PM 22033762
ER
PT J
AU Rudmann, D
Cardiff, R
Chouinard, L
Goodman, D
Kuttler, K
Marxfeld, H
Molinolo, A
Treumann, S
Yoshizawa, K
AF Rudmann, Daniel
Cardiff, Robert
Chouinard, Luc
Goodman, Dawn
Kuettler, Karin
Marxfeld, Heike
Molinolo, Alfredo
Treumann, Silke
Yoshizawa, Katsuhiko
CA INHAND Mammary Zymbal's Preputial
TI Proliferative and Nonproliferative Lesions of the Rat and Mouse Mammary,
Zymbal's, Preputial, and Clitoral Glands
SO TOXICOLOGIC PATHOLOGY
LA English
DT Article
DE rodent; nomenclature; mammary gland; Zymbal's gland; preputial gland;
clitoral gland; neoplasms; nonproliferative
ID BREAST-CANCER; TRANSGENIC MICE; NEU ONCOGENE; TUMORS; EXPRESSION;
CLASSIFICATION; TUMORIGENESIS; CARCINOMA; DIFFERENTIATION; PATHOLOGY
AB The mammary gland of laboratory rodents is an important organ for the evaluation of effects of xenobiotics, especially those that perturb hormonal homeostasis or are potentially carcinogenic. Mammary gland cancer is a leading cause of human mortality and morbidity worldwide and is a subject of major research efforts utilizing rodent models. Zymbal's, preputial, and clitoral glands are standard tissues that are evaluated in animal models that enable human risk assessment of xenobiotics. A widely accepted and utilized international harmonization of nomenclature for mammary, Zymbal's, preputial, and clitoral gland lesions in laboratory animals will improve diagnostic alignment among regulatory and scientific research organizations and enrich international exchanges of information among toxicologists and pathologists.
C1 [Rudmann, Daniel] Eli Lilly & Co, Lilly Res Labs, Indianapolis, IN 46225 USA.
[Cardiff, Robert] Univ Calif Davis, Sch Med, Davis, CA USA.
[Chouinard, Luc] CTBR, Charles Rive Labs, Preclin Serv, Senneville, PQ, Canada.
[Kuettler, Karin; Marxfeld, Heike; Treumann, Silke] BASF SE, Ludwigshafen, Germany.
[Molinolo, Alfredo] Natl Inst Hlth Dent & Craniofacial Res, Bethesda, MD USA.
[Yoshizawa, Katsuhiko] Kansai Med Univ, Moriguchi, Osaka 570, Japan.
RP Rudmann, D (reprint author), Eli Lilly & Co, Lilly Res Labs, 355 E Merrill St, Indianapolis, IN 46225 USA.
EM rudmanndg@lilly.com
NR 76
TC 16
Z9 20
U1 0
U2 4
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0192-6233
EI 1533-1601
J9 TOXICOL PATHOL
JI Toxicol. Pathol.
PD AUG
PY 2012
VL 40
IS 6
SU S
BP 7S
EP 39S
DI 10.1177/0192623312454242
PG 33
WC Pathology; Toxicology
SC Pathology; Toxicology
GA 017UY
UT WOS:000309617700001
PM 22949413
ER
PT J
AU Via, LE
Schimel, D
Weiner, DM
Dartois, V
Dayao, E
Cai, Y
Yoon, YS
Dreher, MR
Kastenmayer, RJ
Laymon, CM
Carny, JE
Flynn, JL
Herscovitch, P
Barry, CE
AF Via, Laura E.
Schimel, Dan
Weiner, Danielle M.
Dartois, Veronique
Dayao, Emmanuel
Cai, Ying
Yoon, Young-Soon
Dreher, Matthew R.
Kastenmayer, Robin J.
Laymon, Charles M.
Carny, J. Eoin
Flynn, JoAnne L.
Herscovitch, Peter
Barry, Clifton E., III
TI Infection Dynamics and Response to Chemotherapy in a Rabbit Model of
Tuberculosis using [F-18]2-Fluoro-Deoxy-D-Glucose Positron Emission
Tomography and Computed Tomography
SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
LA English
DT Article
ID PULMONARY TUBERCULOSIS; MYCOBACTERIUM-TUBERCULOSIS; F-18-FDG PET;
ANTITUBERCULOSIS DRUGS; RISK-FACTORS; LUNG-CANCER; GUINEA-PIGS; DISEASE;
RELAPSE; DIAGNOSIS
AB With a host of new antitubercular chemotherapeutics in development, methods to assess the activity of these agents beyond mouse efficacy are needed to prioritize combinations for clinical trials. Lesions in Mycobacterium tuberculosis-infected rabbits are hypoxic, with histopathologic features that closely resemble those of human tuberculous lesions. Using [F-18]2-fluoro-deoxy-D-glucose ([F-18]FDG) positron emission tomography computed tomography (PET-CT) imaging, we studied the dynamics of tuberculosis infection in rabbits, revealing an initial inflammatory response followed by a consolidative chronic disease. Five weeks after infection, as much as 23% of total lung volume was abnormal, but this was contained and to some extent reversed naturally by 9 weeks. During development of this chronic state, individual lesions in the same animal had very different fates, ranging from complete resolution to significant progression. Lesions that remained through the initial stage showed an increase in volume and tissue density over time by CT. Initiation of chemotherapy using either isoniazid (INH) or rifampin (RIF) during chronic infection reduced bacterial load with quantitative changes in [F-18]FDG uptake, lesion density and total lesion volume measured by CT. The [F-18]FDG PET uptake in lesions was significantly reduced with as little as I week of treatment, while the volume and density of lesions changed more slowly. The results from this study suggest that rabbits may be a useful surrogate species for evaluating novel chemotherapies and understanding changes in both PET and CT scans in human clinical trials.
C1 [Via, Laura E.; Schimel, Dan; Weiner, Danielle M.; Dayao, Emmanuel; Cai, Ying; Yoon, Young-Soon; Barry, Clifton E., III] NIAID, TB Res Sect, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
[Dartois, Veronique] Novartis Inst Trop Dis, Singapore, Singapore.
[Kastenmayer, Robin J.] NIAID, Comparat Med Branch, NIH, Bethesda, MD 20892 USA.
[Dreher, Matthew R.] NIH, Dept Radiol & Imaging Sci, NIH Clin Ctr, Bethesda, MD 20892 USA.
[Laymon, Charles M.; Carny, J. Eoin] Univ Pittsburgh, Dept Radiol, PET Facil, Pittsburgh, PA 15260 USA.
[Flynn, JoAnne L.] Univ Pittsburgh, Dept Mol Genet & Biochem, Pittsburgh, PA USA.
[Herscovitch, Peter] NIH, PET Dept, NIH Clin Ctr, Bethesda, MD 20892 USA.
RP Barry, CE (reprint author), NIAID, TB Res Sect, Lab Clin Infect Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM cbarry@niaid.nih.gov
RI Barry, III, Clifton/H-3839-2012;
OI Via, Laura/0000-0001-6074-9521
FU National Institutes of Health, National Institute of Allergy and
Infectious Disease; Bill & Melinda Gates Foundation; Wellcome Trust
through the Grand Challenges in Global Health Initiative
FX This research was partially supported by the Intramural Research Program
of the National Institutes of Health, National Institute of Allergy and
Infectious Disease, the Bill & Melinda Gates Foundation TB Drug
Accelerator program (PI, Joanne Flynn, University of Pittsburgh), and
the Bill & Melinda Gates Foundation and Wellcome Trust through the Grand
Challenges in Global Health Initiative (PI, Douglas Young, Imperial
College, London).
NR 55
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Z9 33
U1 1
U2 10
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0066-4804
J9 ANTIMICROB AGENTS CH
JI Antimicrob. Agents Chemother.
PD AUG
PY 2012
VL 56
IS 8
BP 4391
EP 4402
DI 10.1128/AAC.00531-12
PG 12
WC Microbiology; Pharmacology & Pharmacy
SC Microbiology; Pharmacology & Pharmacy
GA 979NI
UT WOS:000306826300044
PM 22687508
ER
PT J
AU Nini, L
Zhang, JH
Pandey, M
Panicker, LM
Simonds, WF
AF Nini, Lylia
Zhang, Jian-Hua
Pandey, Mritunjay
Panicker, Leelamma M.
Simonds, William F.
TI Expression of the G beta(5)/R7-RGS protein complex in pituitary and
pancreatic islet cells
SO ENDOCRINE
LA English
DT Letter
ID BETA-SUBUNIT G-BETA-5; NUCLEAR-LOCALIZATION; BRAIN; REGULATORS; MICE;
GENE
C1 [Nini, Lylia; Zhang, Jian-Hua; Pandey, Mritunjay; Panicker, Leelamma M.; Simonds, William F.] NIDDKD, Metab Dis Branch, NIH, Bethesda, MD 20892 USA.
RP Simonds, WF (reprint author), NIDDKD, Metab Dis Branch, NIH, Bldg 10,Room 8C-101,10 Ctr Dr,MSC 1752, Bethesda, MD 20892 USA.
EM wfs@helix.nih.gov
FU Intramural NIH HHS [ZIA DK043304-18, Z01 DK043319-01]
NR 11
TC 2
Z9 2
U1 0
U2 0
PU HUMANA PRESS INC
PI TOTOWA
PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA
SN 1355-008X
J9 ENDOCRINE
JI Endocrine
PD AUG
PY 2012
VL 42
IS 1
BP 214
EP 217
DI 10.1007/s12020-012-9611-5
PG 4
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 011HM
UT WOS:000309155700030
PM 22322946
ER
EF