FN Thomson Reuters Web of Science™
VR 1.0
PT J
AU Fleischhacker, S
Roberts, E
Camplain, R
Evenson, KR
Gittelsohn, J
AF Fleischhacker, Sheila
Roberts, Erica
Camplain, Ricky
Evenson, Kelly R.
Gittelsohn, Joel
TI Promoting Physical Activity Among Native American Youth: a Systematic
Review of the Methodology and Current Evidence of Physical Activity
Interventions and Community-wide Initiatives
SO JOURNAL OF RACIAL AND ETHNIC HEALTH DISPARITIES
LA English
DT Article
DE American Indians; Alaskan Natives; Active living; Physical activity;
Exercise; Obesity
ID OBESITY-PREVENTION PROGRAM; RANDOMIZED CONTROLLED-TRIAL; LIFE-STYLE
INTERVENTION; INDIAN CHILDREN; PARTICIPATORY RESEARCH; UNITED-STATES;
FORMATIVE ASSESSMENT; BODY-COMPOSITION; SCHOOL MEALS; CARDIOVASCULAR
CURRICULUM
AB Promoting physical activity using environmental, policy, and systems approaches could potentially address persistent health disparities faced by American Indian and Alaska Native children and adolescents. To address research gaps and help inform tribally led community changes that promote physical activity, this review examined the methodology and current evidence of physical activity interventions and community-wide initiatives among Native youth. A keyword-guided search was conducted in multiple databases to identify peer-reviewed research articles that reported on physical activity among Native youth. Ultimately, 20 unique interventions (described in 76 articles) and 13 unique community-wide initiatives (described in 16 articles) met the study criteria. Four interventions noted positive changes in knowledge and attitude relating to physical activity but none of the interventions examined reported statistically significant improvements on weight-related outcomes. Only six interventions reported implementing environmental, policy, and system approaches relating to promoting physical activity and generally only shared anecdotal information about the approaches tried. Using community-based participatory research or tribally driven research models strengthened the tribal-research partnerships and improved the cultural and contextual sensitivity of the intervention or community-wide initiative. Few interventions or community-wide initiatives examined multi-level, multi-sector interventions to promote physical activity among Native youth, families, and communities. More research is needed to measure and monitor physical activity within this understudied, high risk group. Future research could also focus on the unique authority and opportunity of tribal leaders and other key stakeholders to use environmental, policy, and systems approaches to raise a healthier generation of Native youth.
C1 [Fleischhacker, Sheila] NIDDKD, Off Nutr Res, NIH, US Dept HHS, Two Democracy Plaza,Room 635, Bethesda, MD 20892 USA.
[Roberts, Erica] Univ Maryland, Sch Publ Hlth, Dept Behav & Community Hlth, 2242 Valley Dr, College Pk, MD 20742 USA.
[Camplain, Ricky] Univ N Carolina, Dept Epidemiol, Gillings Sch Global Publ Hlth, 137 East Franklin St,Suite 303A, Chapel Hill, NC 27514 USA.
[Evenson, Kelly R.] Univ N Carolina, Dept Epidemiol, Gillings Sch Global Publ Hlth, 137 E Franklin St,Suite 306, Chapel Hill, NC 27514 USA.
[Gittelsohn, Joel] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Int Hlth, Ctr Human Nutr, 615 N Wolfe St,Rm W2041, Baltimore, MD 21205 USA.
RP Fleischhacker, S (reprint author), NIDDKD, Off Nutr Res, NIH, US Dept HHS, Two Democracy Plaza,Room 635, Bethesda, MD 20892 USA.
EM sheila.fleischhacker@nih.gov; eblue@umd.edu; camplain@email.unc.edu;
kelly_evenson@unc.edu; jgittels@jhsph.edu
FU Intramural NIH HHS [Z99 DK999999]; NIMH NIH HHS [T32 MH075854]
NR 127
TC 0
Z9 0
U1 8
U2 8
PU SPRINGER INTERNATIONAL PUBLISHING AG
PI CHAM
PA GEWERBESTRASSE 11, CHAM, CH-6330, SWITZERLAND
SN 2197-3792
EI 2196-8837
J9 J RACIAL ETHN HEALTH
JI J. Racial Ethn. Health Disparities
PD DEC
PY 2016
VL 3
IS 4
BP 608
EP 624
DI 10.1007/s40615-015-0180-1
PG 17
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA EC5TN
UT WOS:000388199400007
PM 27294756
ER
PT J
AU Allen, AJ
Kuczmarski, MF
Evans, MK
Zonderman, AB
Waldstein, SR
AF Allen, Allyssa J.
Kuczmarski, Marie Fanelli
Evans, Michele K.
Zonderman, Alan B.
Waldstein, Shari R.
TI Race Differences in Diet Quality of Urban Food-Insecure Blacks and
Whites Reveals Resiliency in Blacks
SO JOURNAL OF RACIAL AND ETHNIC HEALTH DISPARITIES
LA English
DT Article
DE Food insecurity; Diet quality; Health disparities; SNAP; Food stamps;
Race; Urban
ID UNITED-STATES; ADULTS; POVERTY; CONSUMPTION; AMERICANS
AB Introduction Evidence from epidemiological studies shows a link between food insecurity and diet intake or quality. However, the moderating effect of race in this relation has not yet been studied.
Methods Food insecurity (USDA Food Security Module) and diet quality (Healthy Eating Index-2010; HEI) were measured in 1741 participants from the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) study. Data were collected from 2004 to 2009 and analyzed in 2014. Multivariable regression assessed the interaction of race and food insecurity on HEI scores, adjusting for age, sex, poverty status, single parent status, drug, alcohol and cigarette use, and comorbid diseases.
Results The interaction of food insecurity and race was significantly associated with diet quality (p = 0.001). In the absence of food insecurity, HEI scores were similar across race. However, with each food insecurity item endorsed, HEI scores were substantially lower for Whites compared to Blacks. An ad hoc analysis revealed that Blacks were more likely than Whites to participate in SNAP (p < 0.05). Further, race stratified analyses revealed that Blacks participating in SNAP showed diminished associations of food insecurity with diet quality.
Conclusions Study findings provide the first evidence that the influence of food insecurity on diet quality may be potentiated for Whites, but not Blacks. Additionally, results show that Blacks are more likely to participate in SNAP and show attendant buffering of the effects of food insecurity on diet quality. These findings may have important implications for understanding how food insecurity affects diet quality differentially by race.
C1 [Allen, Allyssa J.; Waldstein, Shari R.] Univ Maryland Baltimore Cty, Dept Psychol, 1000 Hilltop Circle, Baltimore, MD 21250 USA.
[Kuczmarski, Marie Fanelli; Evans, Michele K.; Zonderman, Alan B.] NIA, Baltimore, MD 21224 USA.
[Kuczmarski, Marie Fanelli] Univ Delaware, Dept Behav Hlth & Nutr, Newark, DE USA.
RP Allen, AJ (reprint author), Univ Maryland Baltimore Cty, Dept Psychol, 1000 Hilltop Circle, Baltimore, MD 21250 USA.
EM allyssaallen@gmail.com
FU NIA NIH HHS [R01 AG034161]
NR 24
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U1 0
U2 0
PU SPRINGER INTERNATIONAL PUBLISHING AG
PI CHAM
PA GEWERBESTRASSE 11, CHAM, CH-6330, SWITZERLAND
SN 2197-3792
EI 2196-8837
J9 J RACIAL ETHN HEALTH
JI J. Racial Ethn. Health Disparities
PD DEC
PY 2016
VL 3
IS 4
BP 706
EP 712
DI 10.1007/s40615-015-0189-5
PG 7
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA EC5TN
UT WOS:000388199400016
PM 27294760
ER
PT J
AU Moore, JC
Mulligan, TS
Yordan, NT
Castranova, D
Pham, VN
Tang, Q
Lobbardi, R
Anselmo, A
Liwski, RS
Berman, JN
Sadreyev, RI
Weinstein, BM
Langenau, DM
AF Moore, John C.
Mulligan, Timothy S.
Yordan, Nora Torres
Castranova, Daniel
Pham, Van N.
Tang, Qin
Lobbardi, Riadh
Anselmo, Anthony
Liwski, Robert S.
Berman, Jason N.
Sadreyev, Ruslan I.
Weinstein, Brant M.
Langenau, David M.
TI T Cell Immune Deficiency in zap70 Mutant Zebrafish
SO MOLECULAR AND CELLULAR BIOLOGY
LA English
DT Article
ID SEVERE COMBINED IMMUNODEFICIENCY; TRANSGENIC ZEBRAFISH; VASCULAR
DEVELOPMENT; TYROSINE KINASE; EMBRYONAL RHABDOMYOSARCOMA; SYK; ZAP-70;
TRANSPLANTATION; EXPRESSION; MICE
AB ZAP70 [zeta-chain (TCR)-associated protein kinase, 70-kDa], is required for T cell activation. ZAP70 deficiencies in humans and null mutations in mice lead to severe combined immune deficiency. Here, we describe a zap70 loss-of-function mutation in zebrafish (zap70(y442)) that was created using transcription activator-like effector nucleases (TALENs). In contrast to what has been reported for morphant zebrafish, zap70(y442) homozygous mutant zebrafish displayed normal development of blood and lymphatic vasculature. Hematopoietic cell development was also largely unaffected in mutant larvae. However, mutant fish had reduced lck: GFP(+) thymic T cells by 5 days postfertilization that persisted into adult stages. Morphological analysis, RNA sequencing, and single-cell gene expression profiling of whole kidney marrow cells of adult fish revealed complete loss of mature T cells in zap70(y442) mutant animals. T cell immune deficiency was confirmed through transplantation of unmatched normal and malignant donor cells into zap70(y442) mutant zebrafish, with T cell loss being sufficient for robust allogeneic cell engraftment. zap70 mutant zebrafish show remarkable conservation of immune cell dysfunction as found in mice and humans and will serve as a valuable model to study zap70 immune deficiency.
C1 [Moore, John C.; Tang, Qin; Lobbardi, Riadh; Langenau, David M.] Massachusetts Gen Hosp, Mol Pathol, Charlestown, MA 02129 USA.
[Moore, John C.; Tang, Qin; Lobbardi, Riadh; Langenau, David M.] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA.
[Moore, John C.; Tang, Qin; Lobbardi, Riadh; Langenau, David M.] Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA.
[Moore, John C.; Yordan, Nora Torres; Tang, Qin; Lobbardi, Riadh; Langenau, David M.] Harvard Stem Cell Inst, Cambridge, MA 02138 USA.
[Mulligan, Timothy S.; Castranova, Daniel; Pham, Van N.; Weinstein, Brant M.] NICHD, Mol Genet Lab, NIH, Bethesda, MD 20892 USA.
[Yordan, Nora Torres] Harvard Univ, Cambridge, MA 02138 USA.
[Anselmo, Anthony; Sadreyev, Ruslan I.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA.
[Anselmo, Anthony] Harvard Med Sch, Dept Genet, Boston, MA USA.
[Liwski, Robert S.; Berman, Jason N.] Dalhousie Univ, Izaak Walton Killam Hlth Ctr, Halifax, NS, Canada.
[Sadreyev, Ruslan I.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Sadreyev, Ruslan I.] Harvard Med Sch, Boston, MA USA.
RP Langenau, DM (reprint author), Massachusetts Gen Hosp, Mol Pathol, Charlestown, MA 02129 USA.; Langenau, DM (reprint author), Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA.; Langenau, DM (reprint author), Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA.; Langenau, DM (reprint author), Harvard Stem Cell Inst, Cambridge, MA 02138 USA.; Weinstein, BM (reprint author), NICHD, Mol Genet Lab, NIH, Bethesda, MD 20892 USA.
EM flyingfish2@nih.gov; dlangenau@mgh.harvard.edu
FU HHS \ National Institutes of Health (NIH) [R01CA154923, U54CA168512];
HHS \ NIH \ NIH Office of the Director (OD) [R24OD016761]; HHS \ NIH \
Eunice Kennedy Shriver National Institute of Child Health and Human
Development (NICHD) [ZIA-HD008808]
FX This work, including the efforts of John Moore, Nora Torres Yordan, Qin
Tang, Riadh Lobbardi, and David Langenau, was funded by HHS vertical bar
National Institutes of Health (NIH) (R01CA154923). This work, including
the efforts of John Moore, Nora Torres Yordan, Qin Tang, Riadh Lobbardi,
and David Langenau, was funded by HHS vertical bar National Institutes
of Health (NIH) (U54CA168512). This work, including the efforts of John
Moore, Nora Torres Yordan, Qin Tang, Riadh Lobbardi, and David Langenau,
was funded by HHS vertical bar NIH vertical bar NIH Office of the
Director (OD) (R24OD016761). This work, including the efforts of Timothy
Mulligan, Daniel Castranova, Van Pham, and Brant Weinstein, was funded
by HHS vertical bar NIH vertical bar Eunice Kennedy Shriver National
Institute of Child Health and Human Development (NICHD) (ZIA-HD008808).
NR 41
TC 0
Z9 0
U1 4
U2 4
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0270-7306
EI 1098-5549
J9 MOL CELL BIOL
JI Mol. Cell. Biol.
PD DEC
PY 2016
VL 36
IS 23
BP 2868
EP 2876
DI 10.1128/MCB.00281-16
PG 9
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA EC9MU
UT WOS:000388469500001
ER
PT J
AU Roy, A
Kundu, M
Jana, M
Mishra, RK
Yung, YN
Luan, CH
Gonzalez, FJ
Pahan, K
AF Roy, Avik
Kundu, Madhuchhanda
Jana, Malabendu
Mishra, Rama K.
Yung, Yeni
Luan, Chi-Hao
Gonzalez, Frank J.
Pahan, Kalipada
TI Identification and characterization of PPAR alpha ligands in the
hippocampus
SO NATURE CHEMICAL BIOLOGY
LA English
DT Article
ID PROLIFERATOR-ACTIVATED-RECEPTOR; RAT HIPPOCAMPUS; UP-REGULATION;
BODY-WEIGHT; MOUSE MODEL; BRAIN; OLEOYLETHANOLAMIDE; EXPRESSION;
NEURONS; DISEASE
AB Peroxisome proliferator-activated receptor-alpha (PPAR alpha) regulates hepatic fatty acid catabolism and mediates the metabolic response to starvation. Recently we found that PPAR alpha is constitutively activated in nuclei of hippocampal neurons and controls plasticity via direct transcriptional activation of CREB. Here we report the discovery of three endogenous PPAR alpha ligands3- hydroxy-(2,2)-dimethyl butyrate, hexadecanamide, and 9-octadecenamide-in mouse brain hippocampus. Mass spectrometric detection of these compounds in mouse hippocampal nuclear extracts, in silico interaction studies, time-resolved FRET analyses, and thermal shift assay results clearly indicated that these three compounds served as ligands of PPAR alpha. Site-directed mutagenesis studies further revealed that PPAR alpha Y464 and Y314 are involved in binding these hippocampal ligands. Moreover, these ligands activated PPAR alpha and upregulated the synaptic function of hippocampal neurons. These results highlight the discovery of hippocampal ligands of PPAR alpha capable of modulating synaptic functions.
C1 [Roy, Avik; Kundu, Madhuchhanda; Jana, Malabendu; Pahan, Kalipada] Rush Univ, Med Ctr, Dept Neurol Sci, Chicago, IL 60612 USA.
[Mishra, Rama K.] Northwestern Univ, Med & Synthet Chem Core, Ctr Mol Innovat & Drug Discovery, Evanston, IL USA.
[Yung, Yeni] Univ Illinois, Res Resources Ctr, Chicago, IL USA.
[Luan, Chi-Hao] Northwestern Univ, High Throughput Anal Lab, Evanston, IL USA.
[Luan, Chi-Hao] Northwestern Univ, Dept Mol Biosci, Evanston, IL USA.
[Gonzalez, Frank J.] NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Pahan, Kalipada] Jesse Brown Vet Affairs Med Ctr, Div Res & Dev, Chicago, IL 60612 USA.
RP Pahan, K (reprint author), Rush Univ, Med Ctr, Dept Neurol Sci, Chicago, IL 60612 USA.; Pahan, K (reprint author), Jesse Brown Vet Affairs Med Ctr, Div Res & Dev, Chicago, IL 60612 USA.
EM kalipada_pahan@rush.edu
FU Chicago Biomedical Consortium; US National Institutes of Health
[AG050431, NS83054]; Veterans Affairs [1I01BX003033-01]
FX The authors thank ChemCore at the Northwestern University Center for
Molecular Innovation and Drug Discovery, which is funded by the Chicago
Biomedical Consortium. This study was supported by grants from the US
National Institutes of Health (AG050431 and NS83054) and a merit award
(1I01BX003033-01) from Veterans Affairs to K.P.
NR 38
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Z9 1
U1 5
U2 5
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1552-4450
EI 1552-4469
J9 NAT CHEM BIOL
JI Nat. Chem. Biol.
PD DEC
PY 2016
VL 12
IS 12
BP 1075
EP +
DI 10.1038/NCHEMBIO.2204
PG 11
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA ED1CZ
UT WOS:000388582900017
PM 27748752
ER
PT J
AU Cressey, TR
Hazra, R
Wiznia, A
Foca, M
Jean-Philippe, P
Graham, B
King, JR
Britto, P
Carey, VJ
Acosta, EP
Yogev, R
AF Cressey, Tim R.
Hazra, Rohan
Wiznia, Andrew
Foca, Marc
Jean-Philippe, Patrick
Graham, Bobbie
King, Jennifer R.
Britto, Paula
Carey, Vincent J.
Acosta, Edward P.
Yogev, Ram
CA IMPAACT P1058A Team
TI Pharmacokinetics of Unboosted Atazanavir in Treatment-experienced
HIV-infected Children, Adolescents and Young Adults
SO PEDIATRIC INFECTIOUS DISEASE JOURNAL
LA English
DT Article
DE pharmacokinetics; antiretrovirals; atazanavir; pediatrics
ID EFFICACY; INFANTS
AB HIV protease inhibitor use in pediatrics is challenging due to the poor palatability and/or toxicity of concomitant low-dose ritonavir. Atazanavir without ritonavir (unboosted) is not recommended for patients with prior virologic failure, a common problem for perinatally-infected adolescents. Atazanavir 400 mg once-daily provided suboptimal exposure. Higher unboosted doses or splitting the daily dose to twice-daily warrants investigation in this treatment-experienced population.
C1 [Cressey, Tim R.] Chiang Mai Univ, Dept Med Technol, Fac Associated Med Sci, Program HIV Prevent & Treatment IRD UMI 174, Chiang Mai, Thailand.
[Cressey, Tim R.; Britto, Paula; Carey, Vincent J.] Harvard TH Chan Sch Publ Hlth, Boston, MA USA.
[Hazra, Rohan] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Maternal & Pediat Infect Dis Branch, Bethesda, MD USA.
[Wiznia, Andrew] Jacobi Med Ctr, Bronx, NY USA.
[Foca, Marc] Columbia Univ, Med Ctr, New York, NY USA.
[Jean-Philippe, Patrick] HJF DAIDS, Bethesda, MD USA.
[Graham, Bobbie] Frontier Sci & Technol, Amherst, NY USA.
[King, Jennifer R.; Acosta, Edward P.] Univ Alabama Birmingham, Birmingham, AL USA.
[Yogev, Ram] Northwestern Univ, Childrens Mem Hosp, Feinberg Sch Med, Chicago, IL 60614 USA.
RP Cressey, TR (reprint author), Fac Associated Med Sci, Dept Med Technol, PHPT IRD UMI 174, 6th Floor,110 Inthawaroros Rd, Mueang Chiang Mai 50200, Thailand.
EM tim.cressey@phpt.org
FU National Institute of Allergy and Infectious Diseases (NIAID) of the
National Institutes of Health (NIH) [UM1AI068632, UM1AI068616,
UM1AI106716]; Eunice Kennedy Shriver National Institute of Child Health
and Human Development (NICHD); National Institute of Mental Health
(NIMH); NIAID, NIH, Department of Health and Human Services
[HHSN272200800014C]
FX The authors would like to thank the patients, families, investigators,
and trial site personnel for their contributions to the study. Overall
support for the International Maternal Pediatric Adolescent AIDS
Clinical Trials Group (IMPAACT) was provided by the National Institute
of Allergy and Infectious Diseases (NIAID) of the National Institutes of
Health (NIH) under Award Numbers UM1AI068632 (IMPAACT LOC), UM1AI068616
(IMPAACT SDMC) and UM1AI106716 (IMPAACT LC), with co-funding from the
Eunice Kennedy Shriver National Institute of Child Health and Human
Development (NICHD) and the National Institute of Mental Health (NIMH).
This project has been funded in whole or in part with federal funds from
the NIAID, NIH, Department of Health and Human Services, under Contract
No. HHSN272200800014C.
NR 11
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U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0891-3668
EI 1532-0987
J9 PEDIATR INFECT DIS J
JI Pediatr. Infect. Dis. J.
PD DEC
PY 2016
VL 35
IS 12
BP 1333
EP 1335
DI 10.1097/INF.0000000000001320
PG 3
WC Immunology; Infectious Diseases; Pediatrics
SC Immunology; Infectious Diseases; Pediatrics
GA EC6AH
UT WOS:000388217900017
PM 27583590
ER
PT J
AU Liu, S
Comandur, R
Jones, CP
Tsang, P
Musier-Forsyth, K
AF Liu, Sheng
Comandur, Roopa
Jones, Christopher P.
Tsang, Pearl
Musier-Forsyth, Karin
TI Anticodon-like binding of the HIV-1 tRNA-like element to human
lysyl-tRNA synthetase
SO RNA
LA English
DT Article
DE anticodon-binding domain; human lysyl-tRNA synthetase; tRNA-like
element; HIV-1 genome; NMR; chemical shift perturbation
ID N-15 RESONANCE ASSIGNMENT; N-TERMINAL DOMAIN; TRNA(LYS); AMINOACYLATION;
RECOGNITION; COMPLEX; MIMICRY; C-13; H-1
AB A critical step in the HIV-1 lifecycle involves reverse transcription of the viral genomic RNA (gRNA). Human tRNA(LYs3) serves as a primer for transcription initiation and is selectively enriched in virus particles. Human lysyl-tRNA synthetase (hLysRS) is also packaged into virions. Recently, a tRNA-like element (TLE) within the HIV-1 gRNA was shown to mimic the global tRNA fold and bind competitively to hLysRS, suggesting a mechanism of tRNA targeting to the primer binding site (PBS) and release from the synthetase. Here, we use NMR to investigate hLysRS anticodon-binding domain (ACB) binding to six RNA oligonucleotides, including a hairpin derived from the HIV-1 gRNA TLE. We show that ACB interacts with submicromolar affinity to U-rich RNA oligonucleotides the tRNALYs3 anticodon stem loop (ACSL), the WT TLE, and a nonanucleotide, U9. In contrast, the ACB bound only weakly to two TLE loop mutants and a C9 nonanucleotide. NMR chemical shift perturbations induced by each RNA indicate that the ACSL and the WT TLE both interact with the ACB in a strikingly similar manner. Taken together, these findings support the conclusion that tRNA mimicry by the HIV-1 genome leads to a highly specific protein RNA interaction that facilitates efficient primer release from hLysRS prior to reverse transcription.
C1 [Liu, Sheng; Tsang, Pearl] Univ Cincinnati, Dept Chem, Cincinnati, OH 45221 USA.
[Comandur, Roopa; Jones, Christopher P.; Musier-Forsyth, Karin] Ohio State Univ, Ctr Retrovirus Res, Dept Chem & Biochem, Columbus, OH 43210 USA.
[Comandur, Roopa; Jones, Christopher P.; Musier-Forsyth, Karin] Ohio State Univ, Ctr RNA Biol, Columbus, OH 43210 USA.
[Jones, Christopher P.] NHLBI, Biochem & Biophys Ctr, NIH, Bldg 10, Bethesda, MD 20892 USA.
RP Tsang, P (reprint author), Univ Cincinnati, Dept Chem, Cincinnati, OH 45221 USA.; Musier-Forsyth, K (reprint author), Ohio State Univ, Ctr Retrovirus Res, Dept Chem & Biochem, Columbus, OH 43210 USA.; Musier-Forsyth, K (reprint author), Ohio State Univ, Ctr RNA Biol, Columbus, OH 43210 USA.
EM pearl.tsang@uc.edu; musier@chemistry.ohio-state.edu
FU National Institutes of Health [RO1 GM113887]; University of Cincinnati
LEAF
FX We thank Dr. William Cantara for critical reading of the manuscript.
This work was funded by National Institutes of Health RO1 GM113887 (to
K.M.-F.) and University of Cincinnati LEAF funding (to P.T.).
NR 21
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Z9 0
U1 2
U2 2
PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
PI COLD SPRING HARBOR
PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA
SN 1355-8382
EI 1469-9001
J9 RNA
JI RNA
PD DEC
PY 2016
VL 22
IS 12
BP 1828
EP 1835
DI 10.1261/rna.058081.116
PG 8
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA EC6MV
UT WOS:000388251300004
PM 27852925
ER
PT J
AU Valentine, HA
AF Valentine, Hannah A.
TI Science Has a Gender Problem Women face discrimination of many kinds. We
need a culture change
SO SCIENTIFIC AMERICAN
LA English
DT Editorial Material
C1 [Valentine, Hannah A.] NIH, Sci Workforce Divers, Bldg 10, Bethesda, MD 20892 USA.
RP Valentine, HA (reprint author), NIH, Sci Workforce Divers, Bldg 10, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 2
U2 2
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0036-8733
J9 SCI AM
JI Sci.Am.
PD DEC
PY 2016
VL 315
IS 6
BP 12
EP 12
PG 1
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EC5GM
UT WOS:000388161400013
ER
PT J
AU Long, Y
Xu, M
Li, R
Dai, S
Beers, J
Chen, GK
Soheilian, F
Baxa, U
Wang, MQ
Marugan, JJ
Muro, S
Li, ZY
Brady, R
Zheng, W
AF Long, Yan
Xu, Miao
Li, Rong
Dai, Sheng
Beers, Jeanette
Chen, Guokai
Soheilian, Ferri
Baxa, Ulrich
Wang, Mengqiao
Marugan, Juan J.
Muro, Silvia
Li, Zhiyuan
Brady, Roscoe
Zheng, Wei
TI Induced Pluripotent Stem Cells for Disease Modeling and Evaluation of
Therapeutics for Niemann-Pick Disease Type A
SO STEM CELLS TRANSLATIONAL MEDICINE
LA English
DT Article
DE Niemann-Pick disease type A; Induced pluripotent stem cells;
Differentiated neural stem cells; Cyclodextrin; delta-Tocopherol;
alpha-Tocopherol; Acid sphingomyelinase
ID LYSOSOMAL STORAGE DISORDERS; ENZYME REPLACEMENT; C-DISEASE;
IDENTIFICATION; MICE; CYCLODEXTRIN; PATHOGENESIS; GENE; CHOLESTEROL;
DEFICIENCY
AB Niemann-Pick disease type A (NPA) is a lysosomal storage disease caused by mutations in the SMPD1 gene that encodes acid sphingomyelinase (ASM). Deficiency in ASM function results in lysosomal accumulation of sphingomyelin and neurodegeneration. Currently, there is no effective treatment for NPA. To accelerate drug discovery for treatment of NPA, we generated induced pluripotent stem cells from two patient dermal fibroblast lines and differentiated them into neural stem cells. The NPA neural stem cells exhibit a disease phenotype of lysosomal sphingomyelin accumulation and enlarged lysosomes. By using this disease model, we also evaluated three compounds that reportedly reduced lysosomal lipid accumulation in Niemann-Pick disease type C as well as enzyme replacement therapy with ASM. We found that a-tocopherol, d-tocopherol, hydroxypropyl-beta-cyclodextrin, and ASM reduced sphingomyelin accumulation and enlarged lysosomes in NPA neural stem cells. Therefore, the NPA neural stem cells possess the characteristic NPA disease phenotype that can be ameliorated by tocopherols, cyclodextrin, and ASM. Our results demonstrate the efficacies of cyclodextrin and tocopherols in the NPA cell-based model. Our data also indicate that the NPA neural stem cells can be used as a new cell-based disease model for further study of disease pathophysiology and for high-throughput screening to identify new lead compounds for drug development.
C1 [Long, Yan; Xu, Miao; Li, Rong; Dai, Sheng; Wang, Mengqiao; Marugan, Juan J.; Zheng, Wei] NIH, Natl Ctr Advancing Translat Sci, 9800 Med Ctr Dr,MSC 3375, Bethesda, MD 20892 USA.
[Beers, Jeanette; Chen, Guokai] NHLBI, Ctr Mol Med, NIH, Bldg 10, Bethesda, MD 20892 USA.
[Brady, Roscoe] NINDS, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
[Long, Yan; Li, Zhiyuan] Chinese Acad Sci, Guangzhou Inst Biomed & Hlth, Guangzhou, Guangdong, Peoples R China.
[Xu, Miao; Dai, Sheng] Zhejiang Univ, Sch Med, Sir Run Run Shaw Hosp, Hangzhou, Zhejiang, Peoples R China.
[Chen, Guokai] Univ Macau, Fac Hlth Sci, Macau, Peoples R China.
[Soheilian, Ferri; Baxa, Ulrich] Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Canc Res Technol Program, Electron Microscopy Lab, Frederick, MD USA.
[Muro, Silvia] Univ Maryland, Inst Biosci & Biotechnol Res, College Pk, MD 20742 USA.
[Muro, Silvia] Univ Maryland, Fischell Dept Bioengn, College Pk, MD 20742 USA.
RP Zheng, W (reprint author), NIH, Natl Ctr Advancing Translat Sci, 9800 Med Ctr Dr,MSC 3375, Bethesda, MD 20892 USA.
EM wzheng@mail.nih.gov
RI Zheng, Wei/J-8889-2014
OI Zheng, Wei/0000-0003-1034-0757
FU Intramural Research Programs of the National Center for Advancing
Translational Sciences; China Scholarship Council; National Natural
Science Foundation of China [81503170]; Guangdong Natural Science
Foundation [2016A030313170]; Frederick National Laboratory for Cancer
Research, National Institutes of Health [HHSN26120080001E]; Natural
Science Foundation of Zhejiang Province for Distinguished Young Scholars
[LR14H090001]; National Institutes of Health [R01-HL098416]; University
of Macau [MYRG2015-00228-FHS]
FX This work was supported by the Intramural Research Programs of the
National Center for Advancing Translational Sciences. This work was also
supported by grants from the China Scholarship Council and grants from
the National Natural Science Foundation of China (81503170 to Y.L.) and
Guangdong Natural Science Foundation (2016A030313170 to Y.L.), from
federal funds from the Frederick National Laboratory for Cancer
Research, National Institutes of Health (under contract HHSN26120080001E
to U.B. and F.S.), from the Natural Science Foundation of Zhejiang
Province for Distinguished Young Scholars (LR14H090001 to M.X.), from
the National Institutes of Health (R01-HL098416 to S.M.), and from the
University of Macau (MYRG2015-00228-FHS to G.C.).
NR 39
TC 0
Z9 0
U1 4
U2 4
PU ALPHAMED PRESS
PI DURHAM
PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA
SN 2157-6564
EI 2157-6580
J9 STEM CELL TRANSL MED
JI Stem Cells Transl. Med.
PD DEC
PY 2016
VL 5
IS 12
BP 1644
EP 1655
DI 10.5966/sctm.2015-0373
PG 12
WC Cell & Tissue Engineering
SC Cell Biology
GA EC5TD
UT WOS:000388198200005
PM 27484861
ER
PT J
AU Zhang, WH
Jerneren, F
Lehne, BC
Chen, MH
Luben, RN
Johnston, C
Elshorbagy, A
Eppinga, RN
Scott, WR
Adeyeye, E
Scott, J
Boger, RH
Khaw, KT
van der Harst, P
Wareham, NJ
Vasan, RS
Chambers, JC
Refsum, H
Kooner, JS
AF Zhang, Weihua
Jerneren, Fredrik
Lehne, Benjamin C.
Chen, Ming-Huei
Luben, Robert N.
Johnston, Carole
Elshorbagy, Amany
Eppinga, Ruben N.
Scott, William R.
Adeyeye, Elizabeth
Scott, James
Boeger, Rainer H.
Khaw, Kay-Tee
van der Harst, Pim
Wareham, Nicholas J.
Vasan, Ramachandran S.
Chambers, John C.
Refsum, Helga
Kooner, Jaspal S.
TI Genome-wide association reveals that common genetic variation in the
kallikrein-kinin system is associated with serum L-arginine levels
SO THROMBOSIS AND HAEMOSTASIS
LA English
DT Article
DE Serum L-arginine concentration; genome-wide association; coagulation;
kallikrein-kinin system
ID ANGIOTENSIN-CONVERTING ENZYME; CORONARY-ARTERY-DISEASE; GENOTYPE
IMPUTATION; METABOLITE LEVELS; PLASMA-LEVELS; NITRIC-OXIDE; BRADYKININ;
BLOOD; METAANALYSIS; EXPRESSION
AB L-arginine is the essential precursor of nitric oxide, and is involved in multiple key physiological processes, including vascular and immune function. The genetic regulation of blood L-arginine levels is largely unknown. We performed a genome-wide association study (GWAS) to identify genetic factors determining serum L-arginine levels, amongst 901 Europeans and 1,394 Indian Asians. We show that common genetic variations at the KLKB1 and F12 loci are strongly associated with serum L-arginine levels. The G allele of single nucleotide polymorphism (SNP) rs71640036 (T/G) in KLKB1 is associated with lower serum L-arginine concentrations (10 mu mol/l per allele copy, p=1x10(-24)), while allele T of rs2545801 (T/C) near the F12 gene is associated with lower serum L-arginine levels (7 mu mol/l per allele copy, p=7x10(-12)). Together these two loci explain 7 % of the total variance in serum L-arginine concentrations. The associations at both loci were replicated in independent cohorts with plasma L-arginine measurements ( p<0.004). The two sentinel SNPs are in nearly complete LD with the nonsynonymous SNP rs3733402 at KLKB1 and the 5'-UTR SNP rs1801020 at F12, respectively. SNPs at both loci are associated with blood pressure. Our findings provide new insight into the genetic regulation of L-arginine and its potential relationship with cardiovascular risk.
C1 [Zhang, Weihua; Lehne, Benjamin C.; Chambers, John C.] Imperial Coll London, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England.
[Zhang, Weihua; Jerneren, Fredrik; Adeyeye, Elizabeth; Chambers, John C.; Kooner, Jaspal S.] Ealing Hosp NHS Trust, Dept Cardiol, Uxbridge Rd, Southall, Middx, England.
[Johnston, Carole; Elshorbagy, Amany; Refsum, Helga] Univ Oxford, Dept Pharmacol, Oxford, England.
[Chen, Ming-Huei] NHLBI, Populat Sci Branch, NIH, Framingham, MA USA.
[Luben, Robert N.; Khaw, Kay-Tee] Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England.
[Elshorbagy, Amany] Univ Alexandria, Dept Physiol, Fac Med, Alexandria, Egypt.
[Eppinga, Ruben N.; van der Harst, Pim] Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, Groningen, Netherlands.
[Eppinga, Ruben N.; van der Harst, Pim] Univ Groningen, Univ Med Ctr Groningen, Dept Genet, Groningen, Netherlands.
[Scott, William R.; Scott, James; Kooner, Jaspal S.] Imperial Coll London, Hammersmith Hosp Campus, Natl Heart & Lung Inst, London, England.
[Adeyeye, Elizabeth] Imperial Coll London, Fac Med, South Kensington Campus, London, England.
[Boeger, Rainer H.] Univ Med Ctr Hamburg Eppendorf, Dept Clin Pharmacol & Toxicol, Hamburg, Germany.
[Wareham, Nicholas J.] Univ Cambridge, MRC, Epidemiol Unit, Cambridge, England.
[Vasan, Ramachandran S.] Boston Univ, Sch Med, Sect Prevent Med & Epidemiol & Cardiol, Boston, MA 02118 USA.
[Vasan, Ramachandran S.] Boston Univ, Framingham, MA USA.
[Vasan, Ramachandran S.] NHLBI, Framingham Heart Study, Framingham, MA USA.
[Chambers, John C.; Kooner, Jaspal S.] Imperial Coll Healthcare NHS Trust, London, England.
[Refsum, Helga] Univ Oslo, Inst Basic Med Sci, Dept Nutr, Fac Med, Oslo, Norway.
RP Zhang, WH (reprint author), Imperial Coll London, Sch Publ Hlth, Fac Med, Dept Epidemiol & Biostat, Norfolk Pl, London W2 1PG, England.
EM weihua.zhang@imperial.ac.uk
FU British Heart Foundation [SP/04/002]; Medical Research Council
[G0601966, G0700931, G0401527, G1000143]; Wellcome Trust
[084723/Z/08/Z]; NIHR [RP-PG-0407-10371]; European Union FP7
(EpiMigrant) [279143]; Action on Hearing Loss [G51]; Cancer Research UK
[C864/A8257]; Norwegian research Council; National Heart, Lung and Blood
Institute's Framingham Heart Study [N01-HC-25195]; Affymetrix Inc.
[N02-HL-6-4278]
FX The British Heart Foundation (SP/04/002), the Medical Research Council
(G0601966, G0700931, G0401527, G1000143), the Wellcome Trust
(084723/Z/08/Z), the NIHR (RP-PG-0407-10371), European Union FP7
(EpiMigrant, 279143), Action on Hearing Loss (G51), Cancer Research UK
(C864/A8257), the Norwegian research Council, and the National Heart,
Lung and Blood Institute's Framingham Heart Study (Contract No.
N01-HC-25195) and its contract with Affymetrix Inc. for genotyping
services (Contract No. N02-HL-6-4278).
NR 49
TC 1
Z9 1
U1 1
U2 1
PU SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN
PI STUTTGART
PA HOLDERLINSTRASSE 3, D-70174 STUTTGART, GERMANY
SN 0340-6245
J9 THROMB HAEMOSTASIS
JI Thromb. Haemost.
PD DEC
PY 2016
VL 116
IS 6
BP 1041
EP 1049
DI 10.1160/TH16-02-0151
PG 9
WC Hematology; Peripheral Vascular Disease
SC Hematology; Cardiovascular System & Cardiology
GA ED6MC
UT WOS:000388968700006
PM 27656708
ER
PT J
AU Yakovlev, S
Belkin, AM
Chen, L
Cao, CZ
Zhang, L
Strickland, DK
Medved, L
AF Yakovlev, Sergiy
Belkin, Alexey M.
Chen, Ling
Cao, Chunzhang
Zhang, Li
Strickland, Dudley K.
Medved, Leonid
TI Anti-VLDL receptor monoclonal antibodies inhibit fibrin-VLDL receptor
interaction and reduce fibrin-dependent leukocyte transmigration
SO THROMBOSIS AND HAEMOSTASIS
LA English
DT Article
DE Fibrinogen/fibrin; VLDL receptor; leukocyte transmigration; monoclonal
antibodies
ID DENSITY-LIPOPROTEIN RECEPTOR; ENDOTHELIAL-CELL RECEPTOR; VE-CADHERIN;
BINDING SITE; ALPHA-2-MACROGLOBULIN RECEPTOR; LDL RECEPTOR; MIGRATION;
PROTEIN; IDENTIFICATION; LOCALIZATION
AB Our previous studies revealed that the interaction of fibrin with the very low density lipoprotein receptor (VLDLR) promotes transendothelial migration of leukocytes and thereby inflammation, and localised the fibrin-binding site to CR-domains 2-4 of this receptor. In the present study, we tested interaction of three anti-VLDLR monoclonal antibodies, mAb 1H10, 1H5, and 5F3, with recombinant fragments of VLDLR containing various combinations of its CR-domains and found that the epitopes for mAb 1H10 and mAb 1H5 overlap with the fibrinbinding site of VLDLR. Based on these findings, we hypothesised that mAb 1H10 and mAb 1H5 should inhibit fibrin-VLDLR interaction and modulate leukocyte transmigration. To test this hypothesis, we first demonstrated that these monoclonal antibodies both have high affinity to the fibrin-binding fragments of the VLDL receptor and efficiently inhibit interaction between the VLDLR-binding fragment of fibrin and the fibrin-binding fragments of VLDLR. Next, in the in vitro experiments using leukocyte transendothelial migration assay we found that both monoclonal antibodies efficiently inhibit leukocyte transmigration induced by fibrin mimetic NDSK-II. Finally, in vivo experiments using mouse model of peritonitis revealed that mAb 1H10 and mAb 1H5 both significantly reduce infiltration of leukocytes into the peritoneum. Furthermore, our experiments using mouse model of myocardial ischemia-reperfusion injury revealed that both monoclonal antibodies significantly reduce myocardial injury induced by ischaemia- reperfusion. Thus, the results obtained indicate that monoclonal antibodies 1H10 and 1H5 are novel specific inhibitors of fibrin-VLDLR-dependent leukocyte transmigration pathway. They may represent potential therapeutics for treatment of fibrin-dependent inflammation including myocardial ischaemia-reperfusion injury.
C1 [Yakovlev, Sergiy; Belkin, Alexey M.; Cao, Chunzhang; Zhang, Li; Strickland, Dudley K.; Medved, Leonid] Univ Maryland, Sch Med, Ctr Vasc & Inflammatory Dis, 800 West Baltimore St, Baltimore, MD 21201 USA.
[Yakovlev, Sergiy; Belkin, Alexey M.; Medved, Leonid] Univ Maryland, Sch Med, Dept Biochem & Mol Biol, Baltimore, MD 21201 USA.
[Chen, Ling] Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA.
[Chen, Ling; Cao, Chunzhang; Zhang, Li; Strickland, Dudley K.] Univ Maryland, Sch Med, Dept Physiol, Baltimore, MD 21201 USA.
[Strickland, Dudley K.] Univ Maryland, Sch Med, Dept Surg, Baltimore, MD 21201 USA.
[Belkin, Alexey M.] NIH, Ctr Sci Review, Bldg 10, Bethesda, MD 20892 USA.
RP Medved, L (reprint author), Univ Maryland, Sch Med, Ctr Vasc & Inflammatory Dis, 800 West Baltimore St, Baltimore, MD 21201 USA.
EM Lmedved@som.umaryland.edu
FU National Institutes of Health R01 Grants [HL056051, HL114379, HL120388,
NS082607]
FX This work was supported by National Institutes of Health R01 Grants
HL056051 to L.M., HL114379 and HL120388 to D.K.S, and NS082607 to L.Z.
NR 26
TC 0
Z9 0
U1 1
U2 1
PU SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN
PI STUTTGART
PA HOLDERLINSTRASSE 3, D-70174 STUTTGART, GERMANY
SN 0340-6245
J9 THROMB HAEMOSTASIS
JI Thromb. Haemost.
PD DEC
PY 2016
VL 116
IS 6
BP 1122
EP 1130
DI 10.1160/TH16-04-0333
PG 9
WC Hematology; Peripheral Vascular Disease
SC Hematology; Cardiovascular System & Cardiology
GA ED6MC
UT WOS:000388968700014
PM 27580629
ER
PT J
AU Socias, ME
Volkow, N
Wood, E
AF Socias, M. Eugenia
Volkow, Nora
Wood, Evan
TI Adopting the "cascade of care' framework: an opportunity to close the
implementation gap in addiction care?
SO ADDICTION
LA English
DT Editorial Material
DE Addiction medicine; cascade of care; evidence-based; performance
measures; quality measurement; substance use disorders
ID SUBSTANCE USE DISORDERS; HIV CARE; MEDICINE; ACT
AB Despite a growing number of evidenced-based addiction treatments, a substantial implementation gap in addiction medicine remains. The 'cascade of care' framework can serve as a tool to identify gaps along the continuum of care and tailor interventions to improve the quality of addiction care and outcomes.
C1 [Socias, M. Eugenia; Wood, Evan] Univ British Columbia, St Pauls Hosp, Dept Med, Vancouver, BC, Canada.
[Socias, M. Eugenia; Wood, Evan] St Pauls Hosp, British Columbia Ctr Excellence HIV AIDS, Vancouver, BC, Canada.
[Volkow, Nora] NIDA, NIH, Rockville, MD USA.
RP Wood, E (reprint author), Univ British Columbia, St Pauls Hosp, Dept Med, Vancouver, BC, Canada.; Wood, E (reprint author), St Pauls Hosp, British Columbia Ctr Excellence HIV AIDS, Vancouver, BC, Canada.
EM uhri-ew@cfenet.ubc.ca
FU US National Institute on Drug Abuse [R25-DA037756]; British Columbia
Node of the Canadian Research Initiative on Substance Misuse; Tier 1
Canada Research Chair; Michael Smith Foundation for Health Research
Post-Doctoral fellowship award; Canada Addiction Medicine Research
Fellowship (US National Institute on Drug Abuse) [R25-DA037756]
FX The study was supported by the US National Institute on Drug Abuse
(R25-DA037756) and the British Columbia Node of the Canadian Research
Initiative on Substance Misuse. E.W. is supported by a Tier 1 Canada
Research Chair. M.E.S. is supported by a Michael Smith Foundation for
Health Research Post-Doctoral fellowship award and a Canada Addiction
Medicine Research Fellowship (US National Institute on Drug Abuse,
R25-DA037756).
NR 16
TC 0
Z9 0
U1 4
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0965-2140
EI 1360-0443
J9 ADDICTION
JI Addiction
PD DEC
PY 2016
VL 111
IS 12
BP 2079
EP 2081
DI 10.1111/add.13479
PG 3
WC Substance Abuse; Psychiatry
SC Substance Abuse; Psychiatry
GA EB5KO
UT WOS:000387413400001
PM 27412876
ER
PT J
AU Harada, Y
Tanaka, N
Ichikawa, M
Kamijo, Y
Sugiyama, E
Gonzalez, FJ
Aoyama, T
AF Harada, Yukiko
Tanaka, Naoki
Ichikawa, Motoki
Kamijo, Yuji
Sugiyama, Eiko
Gonzalez, Frank J.
Aoyama, Toshifumi
TI PPAR alpha-dependent cholesterol/testosterone disruption in Leydig cells
mediates 2,4-dichlorophenoxyacetic acid-induced testicular toxicity in
mice
SO ARCHIVES OF TOXICOLOGY
LA English
DT Article
DE 2,4-dichlorophenoxyacetic acid; PPAR alpha; Cholesterol; Leydig cell;
Testosterone; Testicular toxicity
ID ACTIVATED RECEPTOR-ALPHA; PEROXISOME PROLIFERATORS;
2,4,5-TRICHLOROPHENOXYACETIC ACID; ADULT-RAT; CHOLESTEROL; EXPRESSION;
LIVER; 2,4-D; GENE; STEROIDOGENESIS
AB It was reported that 2,4-dichlorophenoxyacetic acid (2,4-D), a commonly used herbicide and a possible endocrine disruptor, can disturb spermatogenesis, but the precise mechanism is not understood. Since 2,4-D is a weak peroxisome proliferator in hepatocytes and peroxisome proliferator-activated receptor alpha (PPAR alpha) is also expressed in Leydig cells, this study aimed to investigate the link between PPAR alpha and 2,4-D-mediated testicular dysfunction. 2,4-D (130 mg/kg/day) was administered to wild-type and Ppara-null mice for 2 weeks, and the alterations in testis and testosterone/cholesterol metabolism in Leydig cells were examined. Treatment with 2,4-D markedly decreased testicular testosterone in wild-type mice, leading to degeneration of spermatocytes and Sertoli cells. The 2,4-D decreased cholesterol levels in Leydig cells of wild-type mice through down-regulating the expression of 3-hydroxy-3-methylglutaryl coenzyme A synthase 1 and reductase, involved in de novo cholesterogenesis. However, the mRNAs encoding the important proteins involved in testosterone synthesis were unchanged by 2,4-D except for CYP17A1, indicating that exhausted cholesterol levels in the cells is a main reason for reduced testicular testosterone. Additionally, pregnancy rate and the number of pups between 2,4-D-treated wild-type male mice and untreated female mice were significantly lower compared with those between untreated couples. These phenomena were not observed in 2,4-D-treated Ppara-null males. Collectively, these results suggest a critical role for PPAR alpha in 2,4-D-induced testicular toxicity due to disruption of cholesterol/testosterone homeostasis in Leydig cells. This study yields novel insights into the possible mechanism of testicular dysfunction and male infertility caused by 2,4-D.
C1 [Harada, Yukiko; Tanaka, Naoki; Aoyama, Toshifumi] Shinshu Univ, Dept Metab Regulat, Grad Sch Med, 3-1-1 Asahi, Matsumoto, Nagano 3908621, Japan.
[Harada, Yukiko] Shinshu Univ, Dept Pediat, Sch Med, Matsumoto, Nagano, Japan.
[Tanaka, Naoki; Kamijo, Yuji] Shinshu Univ, Dept Internal Med, Sch Med, Matsumoto, Nagano, Japan.
[Ichikawa, Motoki] Shinshu Univ, Dept Family & Child Nursing, Sch Hlth Sci, Matsumoto, Nagano, Japan.
[Sugiyama, Eiko] Nagano Prefectural Coll, Dept Nutr Sci, Nagano, Japan.
[Gonzalez, Frank J.] NCI, Lab Metab, NIH, Bethesda, MD 20892 USA.
RP Tanaka, N (reprint author), Shinshu Univ, Dept Metab Regulat, Grad Sch Med, 3-1-1 Asahi, Matsumoto, Nagano 3908621, Japan.; Tanaka, N (reprint author), Shinshu Univ, Dept Internal Med, Sch Med, Matsumoto, Nagano, Japan.
EM naopi@shinshu-u.ac.jp
NR 33
TC 0
Z9 0
U1 3
U2 3
PU SPRINGER HEIDELBERG
PI HEIDELBERG
PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY
SN 0340-5761
EI 1432-0738
J9 ARCH TOXICOL
JI Arch. Toxicol.
PD DEC
PY 2016
VL 90
IS 12
BP 3061
EP 3071
DI 10.1007/s00204-016-1669-z
PG 11
WC Toxicology
SC Toxicology
GA EB9FH
UT WOS:000387697600012
PM 26838045
ER
PT J
AU Ismaili, E
Walsh, S
O'Brien, PMS
Backstrom, T
Brown, C
Dennerstein, L
Eriksson, E
Freeman, EW
Ismail, KMK
Panay, N
Pearlstein, T
Rapkin, A
Steiner, M
Studd, J
Sundstrom-Paromma, I
Endicott, J
Epperson, CN
Halbreich, U
Reid, R
Rubinow, D
Schmidt, P
Yonkers, K
AF Ismaili, Elgerta
Walsh, Sally
O'Brien, Patrick Michael Shaughn
Backstrom, Torbjorn
Brown, Candace
Dennerstein, Lorraine
Eriksson, Elias
Freeman, Ellen W.
Ismail, Khaled M. K.
Panay, Nicholas
Pearlstein, Teri
Rapkin, Andrea
Steiner, Meir
Studd, John
Sundstrom-Paromma, Inger
Endicott, Jean
Epperson, C. Neill
Halbreich, Uriel
Reid, Robert
Rubinow, David
Schmidt, Peter
Yonkers, Kimberley
CA Int Soc Premenstrual Disorders
TI Fourth consensus of the International Society for Premenstrual Disorders
(ISPMD): auditable standards for diagnosis and management of
premenstrual disorder
SO ARCHIVES OF WOMENS MENTAL HEALTH
LA English
DT Article
DE PMS (premenstrual syndrome); PMD (premenstrual disorder); PMDD
(premenstrual disorder/premenstrual dysphoric disorder)
ID SEROTONIN-REUPTAKE INHIBITORS; DYSPHORIC DISORDER; EFFICACY
AB Whilst professional bodies such as the Royal College and the American College of Obstetricians and Gynecologists have well-established standards for audit of management for most gynaecology disorders, such standards for premenstrual disorders (PMDs) have yet to be developed. The International Society of Premenstrual Disorders (ISPMD) has already published three consensus papers on PMDs covering areas that include definition, classification/quantification, clinical trial design and management (American College Obstetricians and Gynecologists 2011; Brown et al. in Cochrane Database Syst Rev 2:CD001396, 2009; Dickerson et al. in Am Fam Physician 67(8):1743-1752, 2003). In this fourth consensus of ISPMD, we aim to create a set of auditable standards for the clinical management of PMDs. All members of the original ISPMD consensus group were invited to submit one or more auditable standards to be eligible in the inclusion of the consensus. Ninety-five percent of members (18/19) responded with at least one auditable standard. A total of 66 auditable standards were received, which were returned to all group members who then ranked the standards in order of priority, before the results were collated. Proposed standards related to the diagnosis of PMDs identified the importance of obtaining an accurate history, that a symptom diary should be kept for 2 months prior to diagnosis and that symptom reporting demonstrates symptoms in the premenstrual phase of the menstrual cycle and relieved by menstruation. Regarding treatment, the most important standards were the use of selective serotonin reuptake inhibitors (SSRIs) as a first line treatment, an evidence-based approach to treatment and that SSRI side effects are properly explained to patients. A set of comprehensive standards to be used in the diagnosis and treatment of PMD has been established, for which PMD management can be audited against for standardised and improved care.
C1 [Ismaili, Elgerta] Univ Hosp North Staffordshire NHS Trust, City Gen Hosp, Dept Obstet & Gynaecol, Newcastle Rd, Stoke On Trent ST4 6QG, Staffs, England.
[Ismaili, Elgerta; Walsh, Sally] Univ Hosp North Midlands, Stoke On Trent, Staffs, England.
[O'Brien, Patrick Michael Shaughn] Keele Univ, Sch Med, Univ Hosp North Staffordshire, Stoke On Trent, Staffs, England.
[Backstrom, Torbjorn] Norrland Univ Hosp, Dept Clin Sci, Umea Neurosteroid Res Ctr, Umea, Sweden.
[Brown, Candace] Univ Tennessee, Dept Psychiat, Memphis, TN USA.
[Brown, Candace] Univ Tennessee, Dept Obstet & Gynecol, Memphis, TN 38103 USA.
[Dennerstein, Lorraine] Univ Melbourne, Dept Psychiat, Melbourne, Vic, Australia.
[Dennerstein, Lorraine] Natl Ageing Res Inst, Melbourne, Vic, Australia.
[Eriksson, Elias] Gothenburg Univ, Inst Neurosci & Physiol, Gothenburg, Sweden.
[Freeman, Ellen W.] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA.
[Freeman, Ellen W.] Univ Penn, Dept Obstet & Gynecol, Philadelphia, PA 19104 USA.
[Ismail, Khaled M. K.] Univ Birmingham, Coll Med & Dent Sci, Sch Clin & Expt Med, Birmingham, W Midlands, England.
[Panay, Nicholas] Chelsea & Westminster Hosp, Dept Obstet & Gynaecol, London, England.
[Pearlstein, Teri] Brown Univ, Dept Psychiat & Human Behav, Warren Alpert Med Sch, Providence, RI 02912 USA.
[Rapkin, Andrea] Univ Calif Los Angeles, David Geffen Sch Med, Dept Obstet & Gynecol, Los Angeles, CA 90095 USA.
[Steiner, Meir] McMaster Univ, Dept Psychiat, 100 West 5th St, Hamilton, ON L8N 3K7, Canada.
[Steiner, Meir] McMaster Univ, Dept Behav Neurosci, 100 West 5th St, Hamilton, ON L8N 3K7, Canada.
[Steiner, Meir] McMaster Univ, Dept Obstet & Gynecol, 100 West 5th St, Hamilton, ON L8N 3K7, Canada.
[Studd, John] Chelsea & Westminster Hosp, Dept Gynaecol, London, England.
[Sundstrom-Paromma, Inger] Uppsala Univ, Dept Womens & Childrens Hlth, Obstet & Gynaecol, S-75185 Uppsala, Sweden.
[Endicott, Jean] Columbia Univ, Dept Psychiat, New York, NY USA.
[Epperson, C. Neill; Yonkers, Kimberley] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA.
[Epperson, C. Neill; Yonkers, Kimberley] Yale Univ, Sch Med, Dept Obstet Gynecol & Reprod Sci, New Haven, CT USA.
[Halbreich, Uriel] SUNY Buffalo, New York, NY USA.
[Halbreich, Uriel] WPA, New York, NY USA.
[Reid, Robert] Queens Univ, Kingston, ON, Canada.
[Rubinow, David] Univ North Carolina Chapel Hill, Chapel Hill, NC USA.
[Schmidt, Peter] NIH, Sect Behav Endocrinol, Bldg 10, Bethesda, MD 20892 USA.
RP Ismaili, E (reprint author), Univ Hosp North Staffordshire NHS Trust, City Gen Hosp, Dept Obstet & Gynaecol, Newcastle Rd, Stoke On Trent ST4 6QG, Staffs, England.; Ismaili, E (reprint author), Univ Hosp North Midlands, Stoke On Trent, Staffs, England.
EM elgertaismaili@virginmedia.com
NR 17
TC 0
Z9 0
U1 6
U2 6
PU SPRINGER WIEN
PI WIEN
PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 WIEN, AUSTRIA
SN 1434-1816
EI 1435-1102
J9 ARCH WOMEN MENT HLTH
JI Arch. Womens Ment. Health
PD DEC
PY 2016
VL 19
IS 6
BP 953
EP 958
DI 10.1007/s00737-016-0631-7
PG 6
WC Psychiatry
SC Psychiatry
GA EB8QT
UT WOS:000387656600002
PM 27378473
ER
PT J
AU Lee, MR
Weerts, EM
AF Lee, Mary R.
Weerts, Elise M.
TI Oxytocin for the treatment of drug and alcohol use disorders
SO BEHAVIOURAL PHARMACOLOGY
LA English
DT Review
DE addiction; alcoholism; dependence; oxytocin; substance-use disorder;
treatment
ID CONDITIONED PLACE PREFERENCE; METHAMPHETAMINE-SEEKING BEHAVIOR; CHRONIC
MORPHINE TREATMENT; MEDIAL PREFRONTAL CORTEX; SOCIAL ANXIETY DISORDER;
PITUITARY-ADRENAL AXIS; NUCLEUS-ACCUMBENS CORE; LONG-TERM ABSTINENCE;
BLOOD-BRAIN-BARRIER; PROLYL-D-LEUCINE
AB There is growing interest in the use of oxytocin (OT) as a potential treatment for alcohol and other substance-use disorders. OT is a neuropeptide that modulates adaptive processes associated with addiction including reward, tolerance, associative learning, memory, and stress responses. OT exerts its effects through interactions with the hypothalamic-pituitary-adrenal axis and multiple neurotransmitter systems including the dopamine mesolimbic reward and corticotrophin-releasing factor stress systems. The effects of OT on stress systems are of high interest, given the strong link between stress, drug use and relapse, and known dysregulation of hypothalamic-pituitary-adrenal-axis activity associated with substance-use disorders. At the same time, the OT system is itself altered by acute or chronic drug exposure. This review summarizes the preclinical and clinical literature on the OT system and its relevance to drug and alcohol addiction. In addition, findings from recent clinical trials conducted in participants with cocaine, cannabis, or alcohol use disorder are included and evidence that OT may help to normalize blunted stress responses, and attenuate withdrawal-associated hypercortisolism, negative mood, and withdrawal symptoms is summarized. (C) 2016 Wolters Kluwer Health, Inc. All rights reserved.
C1 [Lee, Mary R.] NIAAA, Sect Clin Psychoneuroendocrinol & Neuropsychophar, Bethesda, MD USA.
[Lee, Mary R.] NIDA, Bethesda, MD 20892 USA.
[Weerts, Elise M.] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21224 USA.
RP Weerts, EM (reprint author), Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21224 USA.
EM eweerts@jhmi.edu
FU Bench-to-Bedside (B2B) grant - NIH Office of Behavioral and Social
Sciences Research (OBSSR); National Institute on Alcohol Abuse and
Alcoholism (NIAAA) [R21 AA022679]
FX This work was supported by a Bench-to-Bedside (B2B) grant (PI: Mary R.
Lee) funded by the NIH Office of Behavioral and Social Sciences Research
(OBSSR) and by the National Institute on Alcohol Abuse and Alcoholism
(NIAAA) R21 AA022679 (PI: Elise M. Weerts).
NR 122
TC 0
Z9 0
U1 24
U2 24
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0955-8810
EI 1473-5849
J9 BEHAV PHARMACOL
JI Behav. Pharmacol.
PD DEC
PY 2016
VL 27
IS 8
BP 640
EP 648
DI 10.1097/FBP.0000000000000258
PG 9
WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy
SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy
GA EB9KD
UT WOS:000387711900002
PM 27603752
ER
PT J
AU Papadakis, GZ
Millo, C
Sadowski, SM
Bagci, U
Patronas, NJ
AF Papadakis, Georgios Z.
Millo, Corina
Sadowski, Samira M.
Bagci, Ulas
Patronas, Nicholas J.
TI Kidney Tumor in a von Hippel-Lindau (VHL) Patient With Intensely
Increased Activity on Ga-68-DOTA-TATE PET/CT
SO CLINICAL NUCLEAR MEDICINE
LA English
DT Editorial Material
DE von Hippel-Lindau (VHL) disease; Ga-68-DOTA-TATE PET/CT; Kidney tumor;
CT; MRI
ID IMAGING FEATURES; DISEASE
AB Renal and pancreatic cysts and tumors are the most common visceral manifestations of von Hippel-Lindau (VHL) disease, a heritable multisystem cancer syndrome characterized by development of a variety of malignant and benign tumors. We report a case of a VHL patient with multiple renal cystic and complex cystic/solid lesions. The patient underwent Ga-68-DOTA-TATE-PET/CT showing intensely increased activity by a solid lesion which demonstrated enhancement on both CT and MRI scans, raising high suspicion for malignancy. The presented case indicates application of SSTR-imaging using Ga-68-DOTA-conjugated peptides in VHL-patients and emphasizes the need for cautious interpretation of renal parenchyma Ga-68-DOTATATE activity.
C1 [Papadakis, Georgios Z.; Patronas, Nicholas J.] NIH, Radiol & Imaging Sci, Warren Grant Magnuson Clin Ctr CC, Bldg 10, Bethesda, MD 20892 USA.
[Millo, Corina] NIH, Div Nucl Med, RAD & IS, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA.
[Millo, Corina] NCI, Endocrine Oncol Branch, NIH, Bethesda, MD 20892 USA.
[Sadowski, Samira M.] Univ Hosp Geneva, Endocrine & Thorac Surg, Geneva, Switzerland.
[Bagci, Ulas] Univ Cent Florida, CRCV, Elect & Comp Sci Dept, Orlando, FL 32816 USA.
RP Patronas, NJ (reprint author), NIH, Neuroradiol Branch, Warren Grant Magnuson Clin Ctr CC, Bldg 10,Room 1C361X 10 CTR DR,Mail Stop 1182, Bethesda, MD 20814 USA.
EM NPatronas@cc.nih.gov
FU Intramural NIH HHS [Z99 CL999999]
NR 11
TC 1
Z9 1
U1 1
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0363-9762
EI 1536-0229
J9 CLIN NUCL MED
JI Clin. Nucl. Med.
PD DEC
PY 2016
VL 41
IS 12
BP 970
EP 971
DI 10.1097/RLU.0000000000001393
PG 2
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA EC3BI
UT WOS:000387999000029
PM 27749408
ER
PT J
AU Hinkle, SN
Louis, GMB
Rawal, S
Zhu, YY
Albert, PS
Zhang, CL
AF Hinkle, Stefanie N.
Louis, Germaine M. Buck
Rawal, Shristi
Zhu, Yeyi
Albert, Paul S.
Zhang, Cuilin
TI A longitudinal study of depression and gestational diabetes in pregnancy
and the postpartum period
SO DIABETOLOGIA
LA English
DT Article
DE Depression; Gestational diabetes; Postpartum; Pregnancy
ID BIDIRECTIONAL ASSOCIATION; PERINATAL DEPRESSION; PREDICTORS; SYMPTOMS;
MELLITUS; OBESITY; COHORT; TYPE-2; HYPERGLYCEMIA; OUTCOMES
AB Depression and glucose intolerance commonly co-occur among non-pregnant individuals; however, the temporal relationship between gestational diabetes (GDM) and depression during pregnancy and the postpartum period is less understood. Our objective was to assess longitudinal associations between depression early in pregnancy and GDM risk, as well as GDM and subsequent risk of postpartum depression.
Data came from the prospective National Institute of Child Health and Human Development Fetal Growth Studies-Singleton cohort (2009-2013), and had been collected at 12 US clinical centres. Pregnant women without psychiatric disorders, diabetes or other chronic conditions before pregnancy were followed throughout pregnancy (n = 2477). Only women with GDM and matched controls were followed up at 6 weeks postpartum (n = 162). GDM was ascertained by a review of the medical records. Depression was assessed in the first (8-13 gestational weeks) and second (16-22 weeks) trimesters and at 6 weeks postpartum using the Edinburgh Postnatal Depression Scale. Postpartum depression was defined as a depressive symptom score aeyen10 or antidepressant medicine use after delivery. RR and 95% CI were adjusted for pre-pregnancy BMI and other risk factors. GDM was considered to be the outcome for the first set of analyses, with depression in the first and second trimesters as the exposures. Postpartum depression was considered as the outcome for the second set of analyses, with GDM as the exposure.
Overall, comparing the highest and lowest quartiles of first-trimester depression scores, the scores from the highest quartile were associated with a significant twofold (95% CI 1.06, 3.78) increased risk of GDM, but this was attenuated to 1.72-fold (95% CI 0.92, 3.23) after adjustment; the second-trimester results were similar. The risk was stronger and significant in both trimesters among non-obese women (p for trend 0.02 and 0.01, respectively), but null for obese women. Women with persistently high depression scores in both trimesters had the greatest risk of GDM (highest vs lowest quartile in both trimesters: adjusted RR 3.21, 95% CI 1.00, 10.28). GDM was associated with an adjusted 4.62-fold (95% CI 1.26, 16.98) increased risk of subsequent postpartum depression.
This prospective study demonstrates a modest association between depressive symptoms early in pregnancy and an increased risk of incident GDM, as well as between GDM and subsequent postpartum depression risk, highlighting pregnancy and the postpartum period as an important susceptible time window during the life course for the interplay between depression and glucose intolerance phenotypes. GDM risk associated with elevated depressive symptoms was particularly high among non-obese women and women with symptoms persisting across the first two trimesters of pregnancy.
C1 [Hinkle, Stefanie N.; Rawal, Shristi; Zhu, Yeyi; Zhang, Cuilin] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Div Intramural Populat Hlth Res, Epidemiol Branch, 6710B Rockledge Dr,MSC 7004, Bethesda, MD 20817 USA.
[Louis, Germaine M. Buck] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Div Intramural Populat Hlth Res, Off Director, Bethesda, MD 20817 USA.
[Albert, Paul S.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Div Intramural Populat Hlth Res, Biostat & Bioinformat Branch, Bethesda, MD 20817 USA.
RP Zhang, CL (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Div Intramural Populat Hlth Res, Epidemiol Branch, 6710B Rockledge Dr,MSC 7004, Bethesda, MD 20817 USA.
EM zhangcu@mail.nih.gov
OI Buck Louis, Germaine/0000-0002-1774-4490
FU Intramural Research Program of the Eunice Kennedy Shriver NICHD;
National Institutes of Health; ARRA [HHSN275200800013C,
HHSN275200800002I, HHSN27500006, HHSN275200800003IC, HHSN275200800014C,
HHSN275200800012C, HHSN275200800028C, HHSN275201000009C]
FX This work was supported by the Intramural Research Program of the Eunice
Kennedy Shriver NICHD, National Institutes of Health and through ARRA
funding (contracts: HHSN275200800013C, HHSN275200800002I, HHSN27500006,
HHSN275200800003IC, HHSN275200800014C, HHSN275200800012C,
HHSN275200800028C, HHSN275201000009C).
NR 38
TC 0
Z9 0
U1 9
U2 9
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0012-186X
EI 1432-0428
J9 DIABETOLOGIA
JI Diabetologia
PD DEC
PY 2016
VL 59
IS 12
BP 2594
EP 2602
DI 10.1007/s00125-016-4086-1
PG 9
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA EB7UN
UT WOS:000387596300016
PM 27640810
ER
PT J
AU Sallard, E
Tallet, J
Thut, G
Deiber, MP
Barral, J
AF Sallard, Etienne
Tallet, Jessica
Thut, Gregor
Deiber, Marie-Pierre
Barral, Jerome
TI Age-related changes in post-movement beta synchronization during a
selective inhibition task
SO EXPERIMENTAL BRAIN RESEARCH
LA English
DT Article
DE Inhibitory control; Electroencephalography; Time-frequency;
Oscillations; Source localization
ID OSCILLATORY CORTICAL ACTIVITY; OLDER-ADULTS; FUNCTIONAL NEUROANATOMY;
BIMANUAL COORDINATION; RESPONSE-INHIBITION; FINGER MOVEMENT; IMAGERY
CONTENT; MOTOR TASK; MEMORY; BRAIN
AB Post-movement beta synchronization (PMBS) modulations have been related to sensory reafferences after movement initiation and inhibitory processes after movement interruption. Although these processes have been separately studied in young and old adults, little is known about the age-related changes in PMBS during selective inhibitory control (i.e. stop a part of an action). The present study examines the age-related modulations of PMBS associated with sensory reafferences and inhibitory processes in selective inhibitory control. Young (n = 17) and old (n = 13) participants performed a switching task first engaging bimanual finger tapping then requiring to stop the left while maintaining the right unimanual tapping (i.e. selective inhibition) at an imperative stimulus. Age groups were compared on behavioral (mean, variability and percentage of errors of inter-tap interval during and after the switching) and electrophysiological (time-frequency and source estimations in the 14-30 Hz beta frequency range) data time-locked on the imperative stimulus. Behaviorally, old adults showed larger variability and percentage of errors during the switching but performed as well as young adults after the switching. Electrophysiologically, PMBS significantly increased after the switching in the old compared to the young group within bilateral frontal and parietal areas. Our results show that the effort to maintain selective inhibition involves increased brain activation in old compared to young adults. The larger PMBS within frontal and parietal regions in old adults may reflect an age-related brain compensation enabling to efficiently maintain post-switching inhibition.
C1 [Sallard, Etienne; Barral, Jerome] Univ Lausanne, Res Grp Inst Sport Sci, Lausanne, Switzerland.
[Tallet, Jessica] INSERM UPS CHU PURPAN, Toulouse Neuroimaging Ctr UMR1214, Pavillon BAUDOT, F-31024 Toulouse, France.
[Thut, Gregor] Univ Glasgow, Inst Neurosci & Psychol, Glasgow, Lanark, Scotland.
[Deiber, Marie-Pierre] Univ Hosp Geneva, Dept Mental Hlth & Psychiat, Biomarkers Vulnerabil Unit, Geneva, Switzerland.
[Deiber, Marie-Pierre] Fac Med, INSERM U1039, La Tronche, France.
[Sallard, Etienne] NINDS, Human Cort Physiol & Stroke Neurorehabil Sect, NIH, Bldg 10,Room 7D50-52, Bethesda, MD 20892 USA.
RP Sallard, E (reprint author), Univ Lausanne, Res Grp Inst Sport Sci, Lausanne, Switzerland.; Sallard, E (reprint author), NINDS, Human Cort Physiol & Stroke Neurorehabil Sect, NIH, Bldg 10,Room 7D50-52, Bethesda, MD 20892 USA.
EM etienne.sallard@gmail.com
RI Centre d'imagerie Biomedicale, CIBM/B-5740-2012; Deiber,
Marie-Pierre/M-5949-2014
FU Center for Biomedical Imaging (CIBM) of Geneva and Lausanne
FX Cartool software has been programmed by Denis Brunet, from the
Functional Brain Mapping Laboratory, Geneva, Switzerland, and supported
by the Center for Biomedical Imaging (CIBM) of Geneva and Lausanne.
NR 64
TC 0
Z9 0
U1 7
U2 7
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0014-4819
EI 1432-1106
J9 EXP BRAIN RES
JI Exp. Brain Res.
PD DEC
PY 2016
VL 234
IS 12
BP 3543
EP 3553
DI 10.1007/s00221-016-4753-y
PG 11
WC Neurosciences
SC Neurosciences & Neurology
GA EB6LV
UT WOS:000387495900014
PM 27531152
ER
PT J
AU Gallea, C
Horovitz, SG
Najee-Ullah, M'A
Hallett, M
AF Gallea, Cecile
Horovitz, Silvina G.
Najee-Ullah, Muslimah 'Ali
Hallett, Mark
TI Impairment of a parieto-premotor network specialized for handwriting in
writer's cramp
SO HUMAN BRAIN MAPPING
LA English
DT Article
DE human; dystonia; motor program; task specificity; neuroimaging
ID FOCAL HAND DYSTONIA; VOXEL-BASED MORPHOMETRY; CORTICAL MOTOR SYSTEM;
FUNCTIONAL CONNECTIVITY; BASAL GANGLIA; CORTEX; BRAIN; PLASTICITY;
STIMULATION; MOVEMENT
AB Handwriting with the dominant hand is a highly skilled task singularly acquired in humans. This skill is the isolated deficit in patients with writer's cramp (WC), a form of dystonia with maladaptive plasticity, acquired through intensive and repetitive motor practice. When a skill is highly trained, a motor program is created in the brain to execute the same movement kinematics regardless of the effector used for the task. The task- and effector-specific symptoms in WC suggest that a problem particularly occurs in the brain when the writing motor program is carried out by the dominant hand. In this MRI study involving 12 WC patients (with symptoms only affecting the right dominant hand during writing) and 15 age matched unaffected controls we showed that: (1) the writing program recruited the same network regardless of the effector used to write in both groups; (2) dominant handwriting recruited a segregated parieto-premotor network only in the control group; (3) local structural alteration of the premotor area, the motor component of this network, predicted functional connectivity deficits during dominant handwriting and symptom duration in the patient group. Dysfunctions and structural abnormalities of a segregated parieto-premotor network in WC patients suggest that network specialization in focal brain areas is crucial for well-learned motor skill. Hum Brain Mapp 37:4363-4375, 2016. (c) 2016 Wiley Periodicals, Inc.
C1 [Gallea, Cecile; Horovitz, Silvina G.; Najee-Ullah, Muslimah 'Ali; Hallett, Mark] NINDS, Human Motor Control Sect, Med Neurol Branch, NIH, 10 Ctr Dr,Bldg 10-7D37, Bethesda, MD 20892 USA.
[Gallea, Cecile] UPMC Univ Paris 06, Ctr Neuroimagerie Rech CENIR, Sorbonne Univ, INSERM,U1127 CNRS,UMR 7225,UMR S 1127,ICM, F-75013 Paris, France.
RP Gallea, C (reprint author), NINDS, Human Motor Control Sect, Med Neurol Branch, NIH, 10 Ctr Dr,Bldg 10-7D37, Bethesda, MD 20892 USA.
EM cecile.gallea.icm@gmail.com
FU NINDS intramural program; Fondation pour la Recherche Medicale (FRM,
"Programme Espoir de la Recherche, Posdoctorat a l'etranger"); NINDS
Competitive Fellowship (intramural program)
FX Contract grant sponsor: NINDS intramural program; Contract grant
sponsor: Fondation pour la Recherche Medicale (FRM, "Programme Espoir de
la Recherche, Posdoctorat a l'etranger") and an NINDS Competitive
Fellowship (intramural program) (to C.G.).
NR 82
TC 0
Z9 0
U1 6
U2 6
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1065-9471
EI 1097-0193
J9 HUM BRAIN MAPP
JI Hum. Brain Mapp.
PD DEC
PY 2016
VL 37
IS 12
BP 4363
EP 4375
DI 10.1002/hbm.23315
PG 13
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA EB5FL
UT WOS:000387399200011
PM 27466043
ER
PT J
AU Taylor, PA
Alhamud, A
van der Kouwe, A
Saleh, MG
Laughton, B
Meintjes, E
AF Taylor, Paul A.
Alhamud, A.
van der Kouwe, Andre
Saleh, Muhammad G.
Laughton, Barbara
Meintjes, Ernesta
TI Assessing the performance of different DTI motion correction strategies
in the presence of EPI distortion correction
SO HUMAN BRAIN MAPPING
LA English
DT Article
DE diffusion tensor imaging; motion correction; echo planar imaging
volumetric navigator; fractional anisotropy; tractography
ID IN-DIFFUSION MRI; SUBJECT-MOTION; WHITE-MATTER; HEAD MOTION; SPIN-ECHO;
TRACTOGRAPHY; REPRODUCIBILITY; ARTIFACTS; IMAGES; BRAIN
AB Diffusion tensor imaging (DTI) is susceptible to several artifacts due to eddy currents, echo planar imaging (EPI) distortion and subject motion. While several techniques correct for individual distortion effects, no optimal combination of DTI acquisition and processing has been determined. Here, the effects of several motion correction techniques are investigated while also correcting for EPI distortion: prospective correction, using navigation; retrospective correction, using two different popular packages (FSL and TORTOISE); and the combination of both methods. Data from a pediatric group that exhibited incidental motion in varying degrees are analyzed. Comparisons are carried while implementing eddy current and EPI distortion correction. DTI parameter distributions, white matter (WM) maps and probabilistic tractography are examined. The importance of prospective correction during data acquisition is demonstrated. In contrast to some previous studies, results also show that the inclusion of retrospective processing also improved ellipsoid fits and both the sensitivity and specificity of group tractographic results, even for navigated data. Matches with anatomical WM maps are highest throughout the brain for data that have been both navigated and processed using TORTOISE. The inclusion of both prospective and retrospective motion correction with EPI distortion correction is important for DTI analysis, particularly when studying subject populations that are prone to motion. Hum Brain Mapp 37:4405-4424, 2016. (c) 2016 Wiley Periodicals, Inc.
C1 [Taylor, Paul A.; Alhamud, A.; Saleh, Muhammad G.; Meintjes, Ernesta] Univ Cape Town, Dept Human Biol, Fac Hlth Sci, MRC UCT Med Imaging Res Unit, Cape Town, South Africa.
[Taylor, Paul A.] African Inst Math Sci, Muizenberg, Western Cape, South Africa.
[Taylor, Paul A.] NIH, Sci & Stat Comp Core, Bldg 10, Bethesda, MD 20892 USA.
[van der Kouwe, Andre] Massachusetts Gen Hosp, Dept Radiol, Boston, MA USA.
[Laughton, Barbara] Univ Stellenbosch, Dept Paediat & Child Hlth, Childrens Infect Dis Clin Res Unit, Stellenbosch, South Africa.
RP Taylor, PA (reprint author), Univ Cape Town, Fac Hlth Sci, Dept Human Biol, ZA-7925 Cape Town, South Africa.
EM neon.taylor@gmail.com
FU NRF/DST South African Research Chairs Initiative; NIH [R01HD071664,
R21MH096559]; NRF [CPR20110614000019421]; Medical Research Council
(MRC); NIMH; NINDS Intramural Research Programs of the NIH
FX Contract grant sponsor: NRF/DST South African Research Chairs
Initiative; Contract grant sponsor: NIH; Contract grant number:
R01HD071664 and R21MH096559; Contract grant sponsor: NRF; Contract grant
number: CPR20110614000019421; Contract grant sponsor: The Medical
Research Council (MRC); Contract grant sponsor: NIMH and NINDS
Intramural Research Programs of the NIH
NR 44
TC 0
Z9 0
U1 2
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1065-9471
EI 1097-0193
J9 HUM BRAIN MAPP
JI Hum. Brain Mapp.
PD DEC
PY 2016
VL 37
IS 12
BP 4405
EP 4424
DI 10.1002/hbm.23318
PG 20
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA EB5FL
UT WOS:000387399200014
PM 27436169
ER
PT J
AU Eleftherianos, I
Castillo, JC
Patrnogic, J
AF Eleftherianos, Ioannis
Castillo, Julio Cesar
Patrnogic, Jelena
TI TGF-beta signaling regulates resistance to parasitic nematode infection
in Drosophila melanogaster
SO IMMUNOBIOLOGY
LA English
DT Article
DE Immunity; Infection; TGF-beta
ID PHOTORHABDUS-ASYMBIOTICA; ENTOMOPATHOGENIC NEMATODES; IMMUNE-RESPONSES;
ADULT FLIES; BACTERIA; INSECT; HOST; MODEL; RECOGNITION; PATHWAY
AB Over the past decade important advances have been made in the field of innate immunity; however, our appreciation of the signaling pathways and molecules that participate in host immune responses to parasitic nematode infections lags behind that of responses to microbial challenges. Here we have examined the regulation and immune activity of Transforming Growth Factor-beta (TGF-beta) signaling in the model host Drosophila melanogaster upon infection with the nematode parasites Heterorhabditis gerrardi and H. bacteriophora containing their mutualistic bacteria Photorhabdus. We have found that the genes encoding the Activin and Bone Morphogenic Protein (BMP) ligands Dawdle (Daw) and Decapentaplegic (Dpp) are transcriptionally induced in flies responding to infection with the nematode parasites, containing or lacking their associated bacteria. We also show that deficient Daw or Dpp regulates the survival of D. melanogaster adults to the pathogens, whereas inactivation of Daw reduces the persistence of the nematodes in the mutant flies. These findings demonstrate a novel role for the TGF-beta signaling pathways in the host anti-nematode immune response. Understanding the molecular mechanisms of host anti-nematode processes will potentially lead to the development of novel means for the efficient control of parasitic nematodes. (C) 2016 Elsevier GmbH. All rights reserved.
C1 [Eleftherianos, Ioannis; Castillo, Julio Cesar; Patrnogic, Jelena] George Washington Univ, Dept Biol Sci, 800 22nd St NW, Washington, DC 20052 USA.
[Castillo, Julio Cesar] NIH, Lab Malaria & Vector Res, Bldg 10, Bethesda, MD 20892 USA.
RP Eleftherianos, I (reprint author), George Washington Univ, Dept Biol Sci, 800 22nd St NW, Washington, DC 20052 USA.
EM ioannise@gwu.edu
FU NIH [1R01AI110675-01, 1R56AI110675-01]
FX We thank members of the Department of Biological Sciences at GWU for
critical reading of the manuscript. The research herein was supported by
NIH grants 1R01AI110675-01 and 1R56AI110675-01.
NR 47
TC 0
Z9 0
U1 5
U2 5
PU ELSEVIER GMBH, URBAN & FISCHER VERLAG
PI JENA
PA OFFICE JENA, P O BOX 100537, 07705 JENA, GERMANY
SN 0171-2985
J9 IMMUNOBIOLOGY
JI Immunobiology
PD DEC
PY 2016
VL 221
IS 12
BP 1362
EP 1368
DI 10.1016/j.imbio.2016.07.011
PG 7
WC Immunology
SC Immunology
GA EC1AF
UT WOS:000387835200005
PM 27473342
ER
PT J
AU Karami, S
Han, Y
Pande, M
Cheng, I
Rudd, J
Pierce, BL
Nutter, EL
Schumacher, FR
Kote-Jarai, Z
Lindstrom, S
Witte, JS
Fang, S
Han, J
Kraft, P
Hunter, DJ
Song, F
Hung, RJ
McKay, J
Gruber, SB
Chanock, SJ
Risch, A
Shen, H
Haiman, CA
Boardman, L
Ulrich, CM
Casey, G
Peters, U
Al Olama, AA
Berchuck, A
Berndt, SI
Bezieau, S
Brennan, P
Brenner, H
Brinton, L
Caporaso, N
Chan, AT
Chang-Claude, J
Christiani, DC
Cunningham, JM
Easton, D
Eeles, RA
Eisen, T
Gala, M
Gallinger, SJ
Gayther, SA
Goode, EL
Gronberg, H
Henderson, BE
Houlston, R
Joshi, AD
Kury, S
Landi, MT
Le Marchand, L
Muir, K
Newcomb, PA
Permuth-Wey, J
Pharoah, P
Phelan, C
Potter, JD
Ramus, SJ
Risch, H
Schildkraut, J
Slattery, ML
Song, H
Wentzensen, N
White, E
Wiklund, F
Zanke, BW
Sellers, TA
Zheng, W
Chatterjee, N
Amos, CI
Doherty, JA
AF Karami, Sara
Han, Younghun
Pande, Mala
Cheng, Iona
Rudd, James
Pierce, Brandon L.
Nutter, Ellen L.
Schumacher, Fredrick R.
Kote-Jarai, Zsofia
Lindstrom, Sara
Witte, John S.
Fang, Shenying
Han, Jiali
Kraft, Peter
Hunter, David J.
Song, Fengju
Hung, Rayjean J.
McKay, James
Gruber, Stephen B.
Chanock, Stephen J.
Risch, Angela
Shen, Hongbing
Haiman, Christopher A.
Boardman, Lisa
Ulrich, Cornelia M.
Casey, Graham
Peters, Ulrike
Al Olama, Ali Amin
Berchuck, Andrew
Berndt, Sonja I.
Bezieau, Stephane
Brennan, Paul
Brenner, Hermann
Brinton, Louise
Caporaso, Neil
Chan, Andrew T.
Chang-Claude, Jenny
Christiani, David C.
Cunningham, Julie M.
Easton, Douglas
Eeles, Rosalind A.
Eisen, Timothy
Gala, Manish
Gallinger, Steven J.
Gayther, Simon A.
Goode, Ellen L.
Gronberg, Henrik
Henderson, Brian E.
Houlston, Richard
Joshi, Amit D.
Kury, Sebastien
Landi, Mari T.
Le Marchand, Loic
Muir, Kenneth
Newcomb, Polly A.
Permuth-Wey, Jenny
Pharoah, Paul
Phelan, Catherine
Potter, John D.
Ramus, Susan J.
Risch, Harvey
Schildkraut, Joellen
Slattery, Martha L.
Song, Honglin
Wentzensen, Nicolas
White, Emily
Wiklund, Fredrik
Zanke, Brent W.
Sellers, Thomas A.
Zheng, Wei
Chatterjee, Nilanjan
Amos, Christopher I.
Doherty, Jennifer A.
CA GECCO
GAME-ON Network CORECT
CORECT
DRIVE
ELLIPSE
FOCI
TRICL
TI Telomere structure and maintenance gene variants and risk of five cancer
types
SO INTERNATIONAL JOURNAL OF CANCER
LA English
DT Article
DE telomere structure; telomere maintenance; cancer risk; GWAS;
meta-analysis; lung cancer; breast cancer; ovarian cancer; prostate
cancer; colorectal cancer
ID GENOME-WIDE ASSOCIATION; SUSCEPTIBILITY LOCI; COLORECTAL-CANCER;
OVARIAN-CANCER; IDENTIFIES 3; METAANALYSIS; LENGTH; IMPUTATION; BREAST;
REGIONS
AB Telomeres cap chromosome ends, protecting them from degradation, double-strand breaks, and end-to-end fusions. Telomeres are maintained by telomerase, a reverse transcriptase encoded by TERT, and an RNA template encoded by TERC. Loci in the TERT and adjoining CLPTM1L region are associated with risk of multiple cancers. We therefore investigated associations between variants in 22 telomere structure and maintenance gene regions and colorectal, breast, prostate, ovarian, and lung cancer risk. We performed subset-based meta-analyses of 204,993 directly-measured and imputed SNPs among 61,851 cancer cases and 74,457 controls of European descent. Independent associations for SNP minor alleles were identified using sequential conditional analysis (with gene-level p value cutoffs <= 3.08 X 10(-5)). Of the thirteen independent SNPs observed to be associated with cancer risk, novel findings were observed for seven loci. Across the DCLRE1B region, rs974494 and rs12144215 were inversely associated with prostate and lung cancers, and colorectal, breast, and prostate cancers, respectively. Across the TERC region, rs75316749 was positively associated with colorectal, breast, ovarian, and lung cancers. Across the DCLRE1B region, rs974404 and rs12144215 were inversely associated with prostate and lung cancers, and colorectal, breast, and prostate cancers, respectively. Near POT1, rs116895242 was inversely associated with colorectal, ovarian, and lung cancers, and RTEL1 rs34978822 was inversely associated with prostate and lung cancers. The complex association patterns in telomere-related genes across cancer types may provide insight into mechanisms through which telomere dysfunction in different tissues influences cancer risk.
C1 [Karami, Sara; Rudd, James; Nutter, Ellen L.; Doherty, Jennifer A.] Geisel Sch Med Dartmouth, Dept Epidemiol, Lebanon, NH USA.
[Han, Younghun; Amos, Christopher I.] Geisel Sch Med Dartmouth, Dept Biomed Data Sci, Lebanon, NH USA.
[Pande, Mala] Univ Texas MD Anderson Canc Ctr, Dept Gastroenterol Hepatol & Nutr, Houston, TX 77030 USA.
[Cheng, Iona] Canc Prevent Inst Calif, Fremont, CA USA.
[Cheng, Iona] Stanford Canc Inst, Stanford, CA USA.
[Pierce, Brandon L.] Univ Chicago, Dept Publ Hlth Sci, Chicago, IL 60637 USA.
[Pierce, Brandon L.] Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA.
[Pierce, Brandon L.] Univ Chicago, Ctr Comprehens Canc, Chicago, IL 60637 USA.
[Schumacher, Fredrick R.; Gruber, Stephen B.; Haiman, Christopher A.; Casey, Graham; Gayther, Simon A.; Henderson, Brian E.; Ramus, Susan J.] Univ Southern Calif, Keck Sch Med, Norris Comprehens Canc Ctr, Dept Prevent Med, Los Angeles, CA USA.
[Kote-Jarai, Zsofia; Eeles, Rosalind A.] Inst Canc Res, Oncogenet Team, London, England.
[Kote-Jarai, Zsofia; Eeles, Rosalind A.] Royal Marsden NHS Fdn Trust, London, England.
[Lindstrom, Sara; Christiani, David C.] Harvard TH Sch Publ Hlth, Program Genet Epidemiol & Stat Genet, Boston, MA USA.
[Witte, John S.] Univ Calif San Francisco, Dept Epidemiol & Biostat, Div Genet & Canc Epidemiol, San Francisco, CA 94143 USA.
[Witte, John S.] Univ Calif San Francisco, Inst Human Genet, San Francisco, CA 94143 USA.
[Fang, Shenying] Univ Texas MD Anderson Canc Ctr, Dept Surg Oncol, Houston, TX 77030 USA.
[Han, Jiali] Indiana Univ, Dept Epidemiol, Fairbanks Sch Publ Hlth, Simon Canc Ctr, Indianapolis, IN 46204 USA.
[Kraft, Peter; Hunter, David J.; Joshi, Amit D.] Harvard Sch Publ Hlth, Dept Epidemiol & Biostat, Boston, MA USA.
[Song, Fengju] Tianjin Med Univ, Canc Inst & Hosp, Natl Clin Res Ctr Canc, Dept Epidemiol & Biostat,Key Lab Canc Prevent & T, Tianjin, Peoples R China.
[Hung, Rayjean J.; Gallinger, Steven J.] Univ Toronto, Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, Toronto, ON, Canada.
[McKay, James; Brennan, Paul] Int Agcy Res Canc, Genet Epidemiol Grp, Genet Canc Susceptibil Grp, Lyon, France.
[Chanock, Stephen J.; Berndt, Sonja I.; Brinton, Louise; Caporaso, Neil; Landi, Mari T.; Wentzensen, Nicolas; Chatterjee, Nilanjan] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Risch, Angela] German Canc Res Ctr, Div Epigen & Canc Risk Factors, Heidelberg, Germany.
[Risch, Angela] German Ctr Lung Res DZL, TLRC H, Heidelberg, Germany.
[Shen, Hongbing] Nanjing Med Univ, Dept Epidemiol & Biostat, Collaborat Innovat Ctr Canc Med,Sch Publ Hlth, Jiangsu Key Lab Canc Biomarkers Prevent & Treatme, Nanjing, Jiangsu, Peoples R China.
[Boardman, Lisa; Cunningham, Julie M.; Goode, Ellen L.] Mayo Clin, Rochester, MN USA.
[Ulrich, Cornelia M.; Slattery, Martha L.] Huntsman Canc Inst, Salt Lake City, UT USA.
[Ulrich, Cornelia M.; Peters, Ulrike; Newcomb, Polly A.; Potter, John D.; White, Emily] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, 1124 Columbia St, Seattle, WA 98104 USA.
[Al Olama, Ali Amin; Easton, Douglas] Univ Cambridge, Dept Publ Hlth & Primary Care, Ctr Canc Genet Epidemiol, Cambridge, England.
[Berchuck, Andrew] Duke Univ, Dept Obstet & Gynecol, Durham, NC USA.
[Bezieau, Stephane; Kury, Sebastien] CHU Nantes, Serv Genet Med, Nantes, France.
[Brenner, Hermann] Deutsch Krebsforschungszentrum, Klin Epidemiol & Alternsforsch, Heidelberg, Germany.
[Chan, Andrew T.; Gala, Manish] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA.
[Chan, Andrew T.] Brigham & Womens Hosp, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA.
[Chan, Andrew T.] Harvard Med Sch, Boston, MA USA.
[Chang-Claude, Jenny] German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany.
[Easton, Douglas; Pharoah, Paul; Song, Honglin] Univ Cambridge, Dept Oncol, Cambridge, England.
[Eisen, Timothy] Addenbrookes Hosp, Cambridge Biomed Campus, Cambridge, England.
[Gronberg, Henrik; Wiklund, Fredrik] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
[Houlston, Richard] Inst Canc Res, London, England.
[Le Marchand, Loic] Univ Hawaii, Ctr Canc, Div Epidemiol, Honolulu, HI 96822 USA.
[Muir, Kenneth] Univ Warwick, Warwick Med Sch, Coventry, W Midlands, England.
[Muir, Kenneth] Univ Manchester, Inst Populat Hlth, Manchester, Lancs, England.
[Permuth-Wey, Jenny; Phelan, Catherine; Sellers, Thomas A.] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA.
[Risch, Harvey] Yale Sch Publ Hlth, New Haven, CT USA.
[Schildkraut, Joellen] Univ Virginia, Charlottesville, VA USA.
[Zanke, Brent W.] Univ Ottawa, Ottawa Hosp, Res Inst, Div Hematol, Ottawa, ON, Canada.
[Zheng, Wei] Vanderbilt Univ, Sch Med, Vanderbilt Epidemiol Ctr, Nashville, TN 37212 USA.
[Zheng, Wei] Vanderbilt Univ, Sch Med, Dept Med, Div Epidemiol, Nashville, TN 37212 USA.
RP Doherty, JA (reprint author), Geisel Sch Med Dartmouth, Dept Community & Family Med, Dept Epidemiol, One Med Ctr Dr,7927 Rubin Bldg,Room 853, Lebanon, NH 03756 USA.
EM Jennifer.A.Doherty@Dartmouth.edu
RI Gallinger, Steven/E-4575-2013; Brenner, Hermann/B-4627-2017; Risch,
Angela/H-2669-2013;
OI Brenner, Hermann/0000-0002-6129-1572; Risch, Angela/0000-0002-8026-5505;
Pierce, Brandon/0000-0002-7829-952X; Houlston,
Richard/0000-0002-5268-0242
FU National Institutes of Health (NIH), National Cancer Institute (NCI)
[R01 CA151989]; European Community's Seventh Framework Programme
[223175, HEALTH-F2-2009-223175]; (COGS), Cancer Research UK
[C1287/A10118, C1287/A 10710, C12292/A11174, C1281/A12014, C5047/A8384,
C5047/A15007, C5047/A10692, C8197/A16565]; National Institutes of Health
[CA128978]; Post-Cancer GWAS initiative [1U19 CA148537, 1U19 CA148065,
1U19 CA148112]; Department of Defense [W81XWH-10-1-0341]; Canadian
Institutes of Health Research (CIHR) for the CIHR Team in Familial Risks
of Breast Cancer; Komen Foundation for the Cure; Breast Cancer Research
Foundation; Ovarian Cancer Research Fund; US NCI GAME-ON Post-GWAS
Initiative [U19-CA148112]; TRICL (Transdisciplinary Research for Cancer
of Lung): NIH [U19 CA148127-01]; Canadian Cancer Society Research
Institute [020214]; DRIVE (Discovery, Biology, and Risk of Inherited
Variants in Breast Cancer): NIH [U19 CA148065]; CORECT (ColoRectal
Transdisciplinary Study): NIH [U19 CA148107, R01 CA81488, P30 CA014089];
ELLIPSE (ELLIPSE, Elucidating Loci in Prostate Cancer Susceptibility);
GAMEON U19 initiative for prostate cancer (ELLIPSE) [U19 CA148537]; FOCI
(Transdisciplinary Cancer Genetic Association and Interacting Studies)
[NIH U19 CA148112-01, R01-CA122443, P50-CA136393, P30-CA15083]; Cancer
Research UK [C490/A8339, C490/A16561, C490/A10119, C490/A10124]; GECCO:
NCI, NIH, U.S. Department of Health and Human Services (DHHS) [U01
CA137088, R01 CA059045]; ASTERISK: a Hospital Clinical Research Program
(PHRC); Regional Council of Pays de la Loire; Groupement des Entreprises
Francaises dans la Lutte contre le Cancer (GEFLUC); Association Anne de
Bretagne Genetique; Ligue Regionale Contre le Cancer (LRCC); COLO23: NIH
[R01 CA60987]; DACHS: German Research Council (Deutsche
Forschungsgemeinschaft) [BR 1704/6-1, BR 1704/6-3, BR 1704/6-4, CH
117/1-1]; German Federal Ministry of Education and Research [01KH0404,
01ER0814]; NIH [R01 CA48998, P01 CA 055075, UM1 CA167552, R01 137178,
R01 CA151993, P50 CA127003, UM1 CA186107, R01 CA137178, P01 CA87969, R01
CA042182]; MEC: NIH [R37 CA54281, P01 CA033619, R01 CA63464]; Ontario
Registry for Studies of Familial Colorectal Cancer (OFCCR: NIH) [U01
CA074783]; Ontario Research Fund; Canadian Institutes of Health
Research; Ontario Institute for Cancer Research (OFCCR); Ontario
Ministry of Research and Innovation; PLCO: Intramural Research Program
of the Division of Cancer Epidemiology and Genetics; Division of Cancer
Prevention, NCI, NIH, DHHS; Cancer Genetic Markers of Susceptibility
(CGEMS) Prostate Cancer GWAS; Nat Genet; Colon CGEMS pancreatic cancer
scan (PanScan); NIH, Genes, Environment and Health Initiative (GEI) [Z01
CP 010200, NIH U01 HG004446, NIH GEI U01 HG 004438]; GENEVA Coordinating
Center; Johns Hopkins University Center for Inherited Disease Research;
PMH: NIH [R01 CA076366]; VITAL: NIH [K05 CA154337]; WHI: National Heart,
Lung, and Blood Institute, NIH, DHHS (The WHI program)
[HHSN268201100046C, HHSN268201100001C, HHSN268201100002C,
HHSN268201100003C, HHSN268201100004C, HHSN271201100004C]; MD Anderson:
NCI [NIH K07CA160753]
FX Grant sponsor: The National Institutes of Health (NIH), National Cancer
Institute (NCI); Grant number: R01 CA151989; Grant sponsor: European
Community's Seventh Framework Programme under grant agreement no 223175;
Grant number: HEALTH-F2-2009-223175; Grant sponsor: (COGS), Cancer
Research UK; Grant numbers: C1287/A10118, C1287/A 10710, C12292/A11174,
C1281/A12014, C5047/ A8384, C5047/A15007, C5047/A10692, C8197/A16565;
Grant sponsor: National Institutes of Health; Grant number: CA128978;
Grant sponsor: Post-Cancer GWAS initiative; Grant numbers: 1U19
CA148537, 1U19 CA148065 and 1U19 CA148112 -the GAME-ON initiative; Grant
sponsor: Department of Defense; Grant number: W81XWH-10-1-0341; Grant
sponsors: Canadian Institutes of Health Research (CIHR) for the CIHR
Team in Familial Risks of Breast Cancer, Komen Foundation for the Cure,
the Breast Cancer Research Foundation, and the Ovarian Cancer Research
Fund; Grant sponsor: US NCI GAME-ON Post-GWAS Initiative; Grant number:
U19-CA148112; Grant sponsor: TRICL (Transdisciplinary Research for
Cancer of Lung): NIH U19 CA148127-01 (PI: Amos); Grant sponsors:
Canadian Cancer Society Research Institute (no. 020214, PI: Hung); DRIVE
(Discovery, Biology, and Risk of Inherited Variants in Breast Cancer):
NIH U19 CA148065; CORECT (ColoRectal Transdisciplinary Study): NIH U19
CA148107; R01 CA81488, P30 CA014089; ELLIPSE (ELLIPSE, Elucidating Loci
in Prostate Cancer Susceptibility); Grant sponsors: GAMEON U19
initiative for prostate cancer (ELLIPSE); Grant number: U19 CA148537;
Grant sponsor: FOCI (Transdisciplinary Cancer Genetic Association and
Interacting Studies); Grant numbers: NIH U19 CA148112-01 (PI: Sellers),
R01-CA122443, P50-CA136393, P30-CA15083 (PI: Goode); Grant sponsor:
Cancer Research UK; Grant numbers: C490/A8339, C490/A16561, C490/A10119,
C490/A10124 (PI: Pharoah); Grant sponsor: GECCO: NCI, NIH, U.S.
Department of Health and Human Services (DHHS); Grant numbers: U01
CA137088, R01 CA059045; Grant sponsors: ASTERISK: a Hospital Clinical
Research Program (PHRC); Regional Council of Pays de la Loire, the
Groupement des Entreprises Francaises dans la Lutte contre le Cancer
(GEFLUC), the Association Anne de Bretagne Genetique and the Ligue
Regionale Contre le Cancer (LRCC); COLO2&3: NIH (R01 CA60987); Grant
sponsor: DACHS: German Research Council (Deutsche
Forschungsgemeinschaft, BR 1704/6-1, BR 1704/6-3, BR 1704/6-4, and CH
117/1-1), and the German Federal Ministry of Education and Research
(01KH0404 and 01ER0814). DALS: NIH (R01 CA48998 to M. L. Slattery);
Grant sponsor: NIH (HPFS); Grant numbers: P01 CA 055075, UM1 CA167552,
R01 137178, R01 CA151993, P50 CA127003; Grant sponsor: NIH (NHS); Grant
numbers: UM1 CA186107, R01 CA137178, P01 CA87969, R01 CA151993 and P50
CA127003; Grant sponsors: NIH (PHS); Grant number: R01 CA042182; Grant
sponsor: MEC: NIH; Grant numbers: R37 CA54281, P01 CA033619 and R01
CA63464; Grant sponsor: Ontario Registry for Studies of Familial
Colorectal Cancer (OFCCR: NIH); Grant number: U01 CA074783; Grant
sponsors: Ontario Research Fund, the Canadian Institutes of Health
Research, and the Ontario Institute for Cancer Research (OFCCR), Ontario
Ministry of Research and Innovation; Grant sponsors: PLCO: Intramural
Research Program of the Division of Cancer Epidemiology and Genetics and
Division of Cancer Prevention, NCI, NIH, DHHS; Cancer Genetic Markers of
Susceptibility (CGEMS) Prostate Cancer GWAS (Yeager, M et al.;
Genome-wide association study of prostate cancer identifies a second
risk locus at 8q24; Grant sponsors: Nat Genet 2007 May; 39(5): 645-9),
Colon CGEMS pancreatic cancer scan (PanScan) (Amundadottir, L et al.
Genome-wide association study identifies variants in the ABO locus
associated with susceptibility to pancreatic cancer. Nat Genet. 2009
Sep; 41(9): 986-90, and Petersen, GM et al. A genome-wide association
study identifies pancreatic cancer susceptibility loci on chromosomes
13q22.1, 1q32.1 and 5p15.33. Nat Genet. 2010 Mar; 42(3): 224-8), and the
Lung Cancer and Smoking study (Landi MT, et al. A genome-wide
association study of lung cancer identifies a region of chromosome 5p15
associated with risk for adenocarcinoma. Am J Hum Genet. 2009 Nov;
85(5): 679-91); the prostate and PanScan study datasets were accessed
with appropriate approval through the dbGaP online resource
(http://cgems. cancer. gov/data/) accession numbers phs000207. v1. p1
and phs000206. v3. p2, respectively, and the lung datasets were accessed
from the dbGaP website (http://www. ncbi. nlm. nih. gov/gap) through
accession number phs000093.v2.p2; Grant sponsor: NIH, Genes, Environment
and Health Initiative (GEI) (Lung Cancer and Smoking study); Grant
numbers: Z01 CP 010200, NIH U01 HG004446 and NIH GEI U01 HG 004438;
Grant sponsors: GENEVA Coordinating Center provided assistance with
genotype cleaning and general study coordination, and the Johns Hopkins
University Center for Inherited Disease Research conducted genotyping;
Grant sponsor: PMH: NIH; Grant number: R01 CA076366 to P. A. Newcomb;
Grant sponsors: VITAL: NIH; Grant numbers: K05 CA154337; Grant sponsors:
WHI: National Heart, Lung, and Blood Institute, NIH, DHHS (The WHI
program); Grant numbers: HHSN268201100046C, HHSN268201100001C,
HHSN268201100002C, HHSN268201100003C, HHSN268201100004C and
HHSN271201100004C; Grant sponsor: MD Anderson: NCI; Grant number: NIH
K07CA160753 (PI: Pande)
NR 47
TC 0
Z9 0
U1 21
U2 21
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0020-7136
EI 1097-0215
J9 INT J CANCER
JI Int. J. Cancer
PD DEC
PY 2016
VL 139
IS 12
BP 2655
EP 2670
DI 10.1002/ijc.30288
PG 16
WC Oncology
SC Oncology
GA EB8CU
UT WOS:000387619400003
PM 27459707
ER
PT J
AU Hussain, S
Kodavanti, PP
Marshburn, JD
Janoshazi, A
Marinakos, SM
George, M
Rice, A
Wiesner, MR
Garantziotis, S
AF Hussain, Salik
Kodavanti, Preeti P.
Marshburn, Jamie D.
Janoshazi, Agnes
Marinakos, Stella M.
George, Margaret
Rice, Annette
Wiesner, Mark R.
Garantziotis, Stavros
TI Decreased Uptake and Enhanced Mitochondrial Protection Underlie Reduced
Toxicity of Nanoceria in Human Monocyte-Derived Macrophages
SO JOURNAL OF BIOMEDICAL NANOTECHNOLOGY
LA English
DT Article
DE Nanoceria; Nanotoxicity; Monocyte-Derived Macrophages; Mitochondrial
Damage
ID CERIUM OXIDE NANOPARTICLES; DIOXIDE NANOPARTICLES; OXIDATIVE STRESS;
CARBON-BLACK; CEO2 NANOPARTICLES; EPITHELIAL-CELLS; CELLULAR UPTAKE;
SURFACE-AREA; IN-VITRO; LUNG
AB Cerium dioxide nanoparticles (nanoceria), currently used as catalysts including additives to diesel fuel, also present potential as a novel therapeutic agent for disorders involving oxidative stress. However, little is known about the effects of nanoceria on primary human cells involved in the innate immune response. Here, we evaluate nanoceria effects on monocyte derived macrophages (MDMs) from healthy human subjects. Peripheral blood monocytes were isolated from healthy human volunteers. MDMs were obtained by maturing monocytes over a five-day period. MDMs were exposed to well-characterized nanoceria suspensions (0, 5, 10, 20 mu g/mL) for 24 or 48 hours. We evaluated particle uptake, ultrastructural changes, cytotoxicity, and mitochondrial damage in MDMs through transmission electron microscopy (TEM), confocal imaging, flow cytometry, spectrometry, western blots, and immunofluorescence techniques. The role that intracellular concentration of nanoceria plays in the toxicity of MDMs was evaluated by 3D image analysis and compared to monocytes as a nanoceria sensitive cell model. Nanoceria failed to induce cytotoxicity in MDMs at the tested doses. Nanoceria-exposed MDMs showed no mitochondrial damage and displayed significant accumulation of anti-apoptotic proteins (Mcl-1 and Bcl-2) during the maturation process. TEM and confocal analyses revealed efficient uptake of nanoceria by MDMs, however 3D image analyses revealed lower nanoceria accumulation per unit cell volume in MDMs compared to monocytes. Taken together, our results suggest that mitochondrial protection and reduced volume-corrected intracellular nanoparticle concentration account for the lower sensitivity of human MDMs to nanoceria.
C1 [Hussain, Salik; Kodavanti, Preeti P.; Marshburn, Jamie D.; George, Margaret; Rice, Annette; Garantziotis, Stavros] NIEHS, Clin Res Unit, POB 12233, Res Triangle Pk, NC 27709 USA.
[Janoshazi, Agnes] NIEHS, Lab Signal Transduct, POB 12233, Res Triangle Pk, NC 27709 USA.
[Marinakos, Stella M.; Wiesner, Mark R.] Duke Univ, Ctr Environm Implicat NanoTechnol, Durham, NC 27708 USA.
RP Hussain, S (reprint author), NIEHS, Clin Res Unit, POB 12233, Res Triangle Pk, NC 27709 USA.
EM salik.hussain@nih.gov
RI Garantziotis, Stavros/A-6903-2009; Hussain, Salik/O-1687-2016
OI Garantziotis, Stavros/0000-0003-4007-375X;
FU Intramural Research Program of the NIH, National Institute of
Environmental Health Sciences (NIEHS); National Science Foundation
(NSF); Environmental Protection Agency (EPA) under NSF [EF-0830093,
DBI-1266252]; Center for the Environmental Implications of
NanoTechnology (CEINT)
FX This work was supported (in part) by the Intramural Research Program of
the NIH, National Institute of Environmental Health Sciences (NIEHS). A
portion of this work was supported by the National Science Foundation
(NSF) and the Environmental Protection Agency (EPA) under NSF
Cooperative Agreement EF-0830093 and DBI-1266252, Center for the
Environmental Implications of NanoTechnology (CEINT). We wish to
gratefully acknowledge Carl Bortner, Maria Sifre, Kevin Katen, Connie
Cummings and Deloris Sutton for technical assistance and the
contribution of the Clinical Research Unit staff in the recruitment of
human subjects for this study. Any opinions, findings, conclusions or
recommendations expressed in this material are those of the author(s)
and do not necessarily reflect the views of the NSF or the EPA. This
work has not been subjected to EPA review and no official endorsement
should be inferred.
NR 48
TC 0
Z9 0
U1 13
U2 13
PU AMER SCIENTIFIC PUBLISHERS
PI VALENCIA
PA 26650 THE OLD RD, STE 208, VALENCIA, CA 91381-0751 USA
SN 1550-7033
EI 1550-7041
J9 J BIOMED NANOTECHNOL
JI J. Biomed. Nanotechnol.
PD DEC
PY 2016
VL 12
IS 12
BP 2139
EP 2150
DI 10.1166/jbn.2016.2320
PG 12
WC Nanoscience & Nanotechnology; Materials Science, Biomaterials
SC Science & Technology - Other Topics; Materials Science
GA EC0JH
UT WOS:000387786100005
PM 28286432
ER
PT J
AU Auld, DS
Jimenez, M
Yue, K
Busby, S
Chen, YC
Bowes, S
Wendel, G
Smith, T
Zhang, JH
AF Auld, Douglas S.
Jimenez, Marta
Yue, Kimberley
Busby, Scott
Chen, Yu-Chi
Bowes, Scott
Wendel, Greg
Smith, Thomas
Zhang, Ji-Hu
TI Matrix-Based Activity Pattern Classification as a Novel Method for the
Characterization of Enzyme Inhibitors Derived from High-Throughput
Screening
SO JOURNAL OF BIOMOLECULAR SCREENING
LA English
DT Article
DE mode of inhibition; enzyme inhibitors; inhibitor classification; enzyme
assays
ID FIREFLY LUCIFERASE; RNA-POLYMERASE; IDENTIFICATION; DISCOVERY; REPORTER;
ORIGINS; BINDING; DRUGS; MODE
AB One of the central questions in the characterization of enzyme inhibitors is determining the mode of inhibition (MOI). Classically, this is done with a number of low-throughput methods in which inhibition models are fitted to the data. The ability to rapidly characterize the MOI for inhibitors arising from high-throughput screening in which hundreds to thousands of primary inhibitors may need to be characterized would greatly help in lead selection efforts. Here we describe a novel method for determining the MOI of a compound without the need for curve fitting of the enzyme inhibition data. We provide experimental data to demonstrate the utility of this new high-throughput MOI classification method based on nonparametric analysis of the activity derived from a small matrix of substrate and inhibitor concentrations (e.g., from a 4(S) x 4(I) matrix). Lists of inhibitors from four different enzyme assays are studied, and the results are compared with the previously described IC50-shift method for MOI classification. The MOI results from this method are in good agreement with the known MOI and compare favorably with those from the IC50-shift method. In addition, we discuss some advantages and limitations of the method and provide recommendations for utilization of this MOI classification method.
C1 [Auld, Douglas S.; Jimenez, Marta; Yue, Kimberley; Busby, Scott; Chen, Yu-Chi; Bowes, Scott; Wendel, Greg; Smith, Thomas; Zhang, Ji-Hu] Novartis Inst Biomed Res, Ctr Prote Chem, 250 Massachusetts Ave, Cambridge, MA 02139 USA.
[Chen, Yu-Chi] Natl Ctr Adv Translat Sci, Bethesda, MD USA.
RP Zhang, JH (reprint author), Novartis Inst Biomed Res, Ctr Prote Chem, 250 Massachusetts Ave, Cambridge, MA 02139 USA.
EM ji-hu.zhang@novartis.com
NR 24
TC 0
Z9 0
U1 2
U2 2
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1087-0571
EI 1552-454X
J9 J BIOMOL SCREEN
JI J. Biomol. Screen
PD DEC
PY 2016
VL 21
IS 10
BP 1075
EP 1089
DI 10.1177/1087057116667255
PG 15
WC Biochemical Research Methods; Biotechnology & Applied Microbiology;
Chemistry, Analytical
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Chemistry
GA EB9MW
UT WOS:000387720200007
PM 27601436
ER
PT J
AU Dai, S
Li, R
Long, Y
Titus, S
Zhao, JH
Huang, RL
Xia, MH
Zheng, W
AF Dai, Sheng
Li, Rong
Long, Yan
Titus, Steve
Zhao, Jinghua
Huang, Ruili
Xia, Menghang
Zheng, Wei
TI One-Step Seeding of Neural Stem Cells with Vitronectin-Supplemented
Medium for High-Throughput Screening Assays
SO JOURNAL OF BIOMOLECULAR SCREENING
LA English
DT Article
DE high-content screening; high-throughput screening; HTS; induced
pluripotent stem cells; iPSC; neuronal cells; neural stem cells; plate
coating; vitronectin
ID PATIENT; NEURONS; DISEASE; CULTURE; PROGENITORS; EVOLUTION
AB Human neuronal cells differentiated from induced pluripotent cells have emerged as a new model system for the study of disease pathophysiology and evaluation of drug efficacy. Differentiated neuronal cells are more similar in genetics and biological content to human brain cells than other animal disease models. However, culture of neuronal cells in assay plates requires a labor-intensive procedure of plate precoating, hampering its applications in high-throughput screening (HTS). We developed a simplified method with one-step seeding of neural stem cells in assay plates by supplementing the medium with a recombinant human vitronectin (VTN), thus avoiding plate precoating. Robust results were obtained from cell viability, calcium response, and neurite outgrowth assays using this new method. Our data demonstrate that this approach greatly simplifies high-throughput assays using neuronal cells differentiated from human stem cells for translational research.
C1 [Dai, Sheng; Li, Rong; Long, Yan; Titus, Steve; Zhao, Jinghua; Huang, Ruili; Xia, Menghang; Zheng, Wei] NIH, Natl Ctr Adv Translat Sci, 9800 Med Ctr Dr, Bethesda, MD 20892 USA.
[Dai, Sheng] Zhejiang Univ, Sir Run Run Shaw Hosp, Sch Med, Hangzhou, Zhejiang, Peoples R China.
[Long, Yan] Chinese Acad Sci, Guangzhou Inst Biomed & Hlth, Guangzhou, Guangdong, Peoples R China.
RP Zheng, W (reprint author), NIH, Natl Ctr Adv Translat Sci, 9800 Med Ctr Dr, Bethesda, MD 20892 USA.
EM wzheng@mail.nih.gov
RI Zheng, Wei/J-8889-2014
OI Zheng, Wei/0000-0003-1034-0757
FU Intramural Research Program of the National Center for Advancing
Translational Sciences, National Institutes of Health
FX This work was funded by the Intramural Research Program of the National
Center for Advancing Translational Sciences, National Institutes of
Health.
NR 30
TC 0
Z9 0
U1 4
U2 4
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1087-0571
EI 1552-454X
J9 J BIOMOL SCREEN
JI J. Biomol. Screen
PD DEC
PY 2016
VL 21
IS 10
BP 1112
EP 1124
DI 10.1177/1087057116670068
PG 13
WC Biochemical Research Methods; Biotechnology & Applied Microbiology;
Chemistry, Analytical
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Chemistry
GA EB9MW
UT WOS:000387720200010
PM 27647668
ER
PT J
AU Foley, TL
Dorjsuren, D
Dexheimer, TS
Burkart, MD
Wight, WC
Simeonov, A
AF Foley, Timothy L.
Dorjsuren, Dorjbal
Dexheimer, Thomas S.
Burkart, Michael D.
Wight, William C.
Simeonov, Anton
TI A Platform to Enable the Pharmacological Profiling of Small Molecules in
Gel-Based Electrophoretic Mobility Shift Assays
SO JOURNAL OF BIOMOLECULAR SCREENING
LA English
DT Article
DE high-throughput screening (HTS); small-molecule testing; electrophoretic
techniques; enzymatic assays and analyses; electrophoretic mobility
shift assay (EMSA); polyacrylamide gel electrophoresis (PAGE)
ID INHIBITORS; IDENTIFICATION
AB We describe a polyacrylamide gel casting cassette that overcomes limitations of commercially available gel electrophoresis equipment. This apparatus molds a single polyacrylamide gel that can evaluate more than 200 samples in parallel, is loaded with a multichannel pipettor, and is flexible with respect to composition of the separating matrix. We demonstrate its use to characterize inhibitors of enzymes that modify protein and nucleic acid substrates. Throughputs of greater than 1000 samples per day were achieved when this system was paired with a quantitative laser-based imaging system, yielding data of remarkable quality.
C1 [Foley, Timothy L.; Dorjsuren, Dorjbal; Dexheimer, Thomas S.; Simeonov, Anton] NIH, Div Preclin Innovat, Natl Ctr Adv Translat Sci, 9800 Med Ctr Dr, Rockville, MD 20850 USA.
[Burkart, Michael D.] Univ Calif San Diego, Dept Chem & Biochem, La Jolla, CA 92093 USA.
[Wight, William C.] Luxon Engn LLC, San Diego, CA USA.
[Foley, Timothy L.] Pfizer, Primary Pharmacol Grp, Pharmacokinet Dynam & Metabolism New Chem EntE, Groton, CT USA.
[Dexheimer, Thomas S.] Michigan State Univ, Dept Pharmacol & Toxicol, Assay Dev & Drug Repurposing Core Facil, E Lansing, MI 48824 USA.
RP Simeonov, A (reprint author), NIH, Div Preclin Innovat, Natl Ctr Adv Translat Sci, 9800 Med Ctr Dr, Rockville, MD 20850 USA.
EM asimeono@mail.nih.gov
FU intramural research program of the National Center for Advancing
Translational Sciences; NIH [1R03MH083266, R21AI090213]
FX The authors disclosed receipt of the following financial support for the
research, authorship, and/or publication of this article: This research
was supported by the intramural research program of the National Center
for Advancing Translational Sciences, as well as NIH award numbers
1R03MH083266 and R21AI090213 (M.D.B.).
NR 12
TC 0
Z9 0
U1 1
U2 1
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1087-0571
EI 1552-454X
J9 J BIOMOL SCREEN
JI J. Biomol. Screen
PD DEC
PY 2016
VL 21
IS 10
BP 1125
EP 1131
DI 10.1177/1087057116652895
PG 7
WC Biochemical Research Methods; Biotechnology & Applied Microbiology;
Chemistry, Analytical
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Chemistry
GA EB9MW
UT WOS:000387720200011
PM 27269812
ER
PT J
AU Schmidt, KT
Chau, CH
Price, DK
Figg, WD
AF Schmidt, Keith T.
Chau, Cindy H.
Price, Douglas K.
Figg, William D.
TI Precision Oncology Medicine: The Clinical Relevance of Patient-Specific
Biomarkers Used to Optimize Cancer Treatment
SO JOURNAL OF CLINICAL PHARMACOLOGY
LA English
DT Review
DE precision medicine; oncology; molecular targeted therapy;
next-generation sequencing
ID CELL LUNG-CANCER; METASTATIC BREAST-CANCER; IMPLEMENTATION CONSORTIUM
GUIDELINES; THIOPURINE METHYLTRANSFERASE GENOTYPE; 1ST GLOBAL APPROVAL;
BRAF V600 MUTATIONS; GROUP 1-98 TRIAL; PHASE-II TRIAL; OPEN-LABEL;
TRASTUZUMAB EMTANSINE
AB Precision medicine in oncology is the result of an increasing awareness of patient-specific clinical features coupled with the development of genomic-based diagnostics and targeted therapeutics. Companion diagnostics designed for specific drug-target pairs were the first to widely utilize clinically applicable tumor biomarkers (eg, HER2, EGFR), directing treatment for patients whose tumors exhibit a mutation susceptible to an FDA-approved targeted therapy (eg, trastuzumab, erlotinib). Clinically relevant germline mutations in drug-metabolizing enzymes and transporters (eg, TPMT, DPYD) have been shown to impact drug response, providing a rationale for individualized dosing to optimize treatment. The use of multigene expression-based assays to analyze an array of prognostic biomarkers has been shown to help direct treatment decisions, especially in breast cancer (eg, Oncotype DX). More recently, the use of next-generation sequencing to detect many potential actionable cancer molecular alterations is further shifting the 1 gene-1 drug paradigm toward a more comprehensive, multigene approach. Currently, many clinical trials (eg, NCI-MATCH, NCI-MPACT) are assessing novel diagnostic tools with a combination of different targeted therapeutics while also examining tumor biomarkers that were previously unexplored in a variety of cancer histologies. Results from ongoing trials such as the NCI-MATCH will help determine the clinical utility and future development of the precision-medicine approach.
C1 [Schmidt, Keith T.; Figg, William D.] NIH, Clin Pharmacol Program, Off Clin Director, Bldg 10, Bethesda, MD 20892 USA.
[Chau, Cindy H.; Price, Douglas K.; Figg, William D.] NCI, Mol Pharmacol Sect, Genitourinary Malignancies Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA.
RP Figg, WD (reprint author), NCI, Genitourinary Malignancies Branch, Ctr Canc Res, NIH, 9000 Rockville Pike,Bldg 10 Room 5A01, Bethesda, MD 20892 USA.
EM figgw@helix.nih.gov
FU 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. 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
organization imply endorsement by the US Government.
NR 124
TC 3
Z9 3
U1 19
U2 19
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0091-2700
EI 1552-4604
J9 J CLIN PHARMACOL
JI J. Clin. Pharmacol.
PD DEC
PY 2016
VL 56
IS 12
BP 1484
EP 1499
DI 10.1002/jcph.765
PG 16
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA EB8SP
UT WOS:000387661500004
PM 27197880
ER
PT J
AU Alves, MC
Galeano, DC
Santos, WS
Lee, C
Bolch, WE
Hunt, JG
da Silva, AX
Carvalho, AB
AF Alves, M. C.
Galeano, D. C.
Santos, W. S.
Lee, Choonsik
Bolch, Wesley E.
Hunt, John G.
da Silva, A. X.
Carvalho, A. B., Jr.
TI Comparison of the effective dose rate to aircrew members using hybrid
computational phantoms in standing and sitting postures
SO JOURNAL OF RADIOLOGICAL PROTECTION
LA English
DT Article
DE aircrew dosimetry; effective dose conversion coefficients; Monte Carlo
simulation; effective dose rate; sitting phantom
ID COSMIC-RADIATION EXPOSURE; CONVERSION COEFFICIENTS; CREW; ATMOSPHERE;
DOSIMETRY; ORGAN; NURBS
AB Aircraft crew members are occupationally exposed to considerable levels of cosmic radiation at flight altitudes. Since aircrew (pilots and passengers) are in the sitting posture for most of the time during flight, and up to now there has been no data on the effective dose rate calculated for aircrew dosimetry in flight altitude using a sitting phantom, we therefore calculated the effective dose rate using a phantom in the sitting and standing postures in order to compare the influence of the posture on the radiation protection of aircrew members. We found that although the better description of the posture in which the aircrews are exposed, the results of the effective dose rate calculated with the phantom in the sitting posture were very similar to the results of the phantom in the standing posture. In fact we observed only a 1% difference. These findings indicate the adequacy of the use of dose conversion coefficients for the phantom in the standing posture in aircrew dosimetry. We also validated our results comparing the effective dose rate obtained using the standing phantom with values reported in the literature. It was observed that the results presented in this study are in good agreement with other authors (the differences are below 30%) who have measured and calculated effective dose rates using different phantoms.
C1 [Alves, M. C.; Galeano, D. C.; Carvalho, A. B., Jr.] Univ Fed Sergipe, Dept Fis, Campus Prof Jose Aloisio de Campos, BR-100000 Sao Cristovao, SE, Brazil.
[Santos, W. S.] Univ Fed Uberlandia, Inst Fis, INFIS UFU, Caixa Postal 593, BR-38400902 Uberlandia, MG, Brazil.
[Lee, Choonsik] NCI, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20852 USA.
[Bolch, Wesley E.] Univ Florida, Dept Nucl & Radiol Engn, Gainesville, FL 32611 USA.
[Hunt, John G.] Inst Radioprotecao & Dosimetria, Dosimetry Div, BR-22783127 Rio De Janeiro, RJ, Brazil.
[Hunt, John G.] Univ Fed Rio de Janeiro, Dept Nucl Engn, Escola Politecn, BR-21941972 Rio De Janeiro, Brazil.
[Galeano, D. C.] Univ Fed Rondonia, Dept Fis, Porto Velho, RO, Brazil.
RP Alves, MC (reprint author), Univ Fed Sergipe, Dept Fis, Campus Prof Jose Aloisio de Campos, BR-100000 Sao Cristovao, SE, Brazil.
EM alves.materia@gmail.com
FU UFS; CNPq; INCT; CAPES
FX The authors thank UFS, CNPq, INCT and CAPES for the partial financial
support.
NR 31
TC 0
Z9 0
U1 6
U2 6
PU IOP PUBLISHING LTD
PI BRISTOL
PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND
SN 0952-4746
EI 1361-6498
J9 J RADIOL PROT
JI J. Radiol. Prot.
PD DEC
PY 2016
VL 36
IS 4
BP 885
EP 901
DI 10.1088/0952-4746/36/4/885
PG 17
WC Environmental Sciences; Public, Environmental & Occupational Health;
Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical
Imaging
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health; Nuclear Science & Technology; Radiology, Nuclear Medicine &
Medical Imaging
GA EB8YY
UT WOS:000387679200001
PM 27798410
ER
PT J
AU Lack, JB
Lange, JD
Tang, AD
Corbett-Detig, RB
Pool, JE
AF Lack, Justin B.
Lange, Jeremy D.
Tang, Alison D.
Corbett-Detig, Russell B.
Pool, John E.
TI A Thousand Fly Genomes: An Expanded Drosophila Genome Nexus
SO MOLECULAR BIOLOGY AND EVOLUTION
LA English
DT Article
DE Drosophila melanogaster; genomic variation; reference alignment; data
resource
ID GENETIC REFERENCE PANEL; MELANOGASTER; POPULATION; PATTERNS; RESOURCE;
LINES
AB The Drosophila Genome Nexus is a population genomic resource that provides D. melanogaster genomes from multiple sources. To facilitate comparisons across data sets, genomes are aligned using a common reference alignment pipeline which involves two rounds of mapping. Regions of residual heterozygosity, identity-by-descent, and recent population admixture are annotated to enable data filtering based on the user's needs. Here, we present a significant expansion of the Drosophila Genome Nexus, which brings the current data object to a total of 1,121 wild-derived genomes. New additions include 305 previously unpublished genomes from inbred lines representing six population samples in Egypt, Ethiopia, France, and South Africa, along with another 193 genomes added from recently-published data sets. We also provide an aligned D. simulans genome to facilitate divergence comparisons. This improved resource will broaden the range of population genomic questions that can addressed from multi-population allele frequencies and haplotypes in this model species. The larger set of genomes will also enhance the discovery of functionally relevant natural variation that exists within and between populations.
C1 [Lack, Justin B.; Lange, Jeremy D.; Pool, John E.] Univ Wisconsin, Genet Lab, Madison, WI 53706 USA.
[Tang, Alison D.; Corbett-Detig, Russell B.] Univ Calif Berkeley, Dept Integrat Biol, Berkeley, CA 94720 USA.
[Lack, Justin B.] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Corbett-Detig, Russell B.] Univ Calif Santa Cruz, Dept Biomol Engn, Santa Cruz, CA 95064 USA.
RP Pool, JE (reprint author), Univ Wisconsin, Genet Lab, Madison, WI 53706 USA.
EM jpool@wisc.edu
FU NIH [R01 GM111797, F32 GM106594]; USDA Hatch grant [WIS01900]
FX The UW-Madison Center for High Throughput Computing provided
computational assistance and resources for this work. This research was
funded by NIH grants R01 GM111797 to JEP and F32 GM106594 to JBL, and by
USDA Hatch grant WIS01900 to JEP.
NR 23
TC 1
Z9 1
U1 6
U2 6
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0737-4038
EI 1537-1719
J9 MOL BIOL EVOL
JI Mol. Biol. Evol.
PD DEC
PY 2016
VL 33
IS 12
BP 3308
EP 3313
DI 10.1093/molbev/msw195
PG 6
WC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics &
Heredity
SC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics &
Heredity
GA EC2FO
UT WOS:000387925300024
PM 27687565
ER
PT J
AU Kelsey, JS
Cataisson, C
Chen, JQ
Herrmann, MA
Petersen, ME
Baumann, DO
McGowan, KM
Yuspa, SH
Keck, GE
Blumberg, PM
AF Kelsey, Jessica S.
Cataisson, Christophe
Chen, Jinqiu
Herrmann, Michelle A.
Petersen, Mark E.
Baumann, David O.
McGowan, Kevin M.
Yuspa, Stuart H.
Keck, Gary E.
Blumberg, Peter M.
TI Biological activity of the bryostatin analog Merle 23 on mouse epidermal
cells and mouse skin
SO MOLECULAR CARCINOGENESIS
LA English
DT Article
DE PMA; tumor promotion; bryostatin; Merle 23; mouse epidermal cells; skin
cancer
ID PROTEIN-KINASE-C; ESTER TUMOR PROMOTERS; PHORBOL ESTER; CLINICAL
DEVELOPMENT; DOWN-REGULATION; PKC INHIBITORS; IN-VITRO; CANCER; LNCAP;
DELTA
AB Bryostatin 1, a complex macrocyclic lactone, is the subject of multiple clinical trials for cancer chemotherapy. Although bryostatin 1 biochemically functions like the classic mouse skin tumor promoter phorbol 12-myristate 13-acetate (PMA) to bind to and activate protein kinase C, paradoxically, it fails to induce many of the typical phorbol ester responses, including tumor promotion. Intense synthetic efforts are currently underway to develop simplified bryostatin analogs that preserve the critical functional features of bryostatin 1, including its lack of tumor promoting activity. The degree to which bryostatin analogs maintain the unique pattern of biological behavior of bryostatin 1 depends on the specific cellular system and the specific response. Merle 23 is a significantly simplified bryostatin analog that retains bryostatin like activity only to a limited extent. Here, we show that in mouse epidermal cells the activity of Merle 23 was either similar to bryostatin 1 or intermediate between bryostatin 1 and PMA, depending on the specific parameter examined. We then examined the hyperplastic and tumor promoting activity of Merle 23 on mouse skin. Merle 23 showed substantially reduced hyperplasia and was not tumor promoting at a dose comparable to that for PMA. These results suggest that there may be substantial flexibility in the design of bryostatin analogs that retain its lack of tumor promoting activity. (c) 2016 Wiley Periodicals, Inc.
C1 [Kelsey, Jessica S.; Cataisson, Christophe; Yuspa, Stuart H.; Blumberg, Peter M.] NCI, Lab Canc Biol & Genet, Ctr Canc Res, Bldg 37,Room 4048B,37 Convent Dr,MSC 4255, Bethesda, MD 20892 USA.
[Chen, Jinqiu; Herrmann, Michelle A.] NCI, Collaborat Prot Technol Resource, Ctr Canc Res, Bethesda, MD 20892 USA.
[Petersen, Mark E.; Baumann, David O.; McGowan, Kevin M.; Keck, Gary E.] Univ Utah, Dept Chem, Salt Lake City, UT 84112 USA.
RP Blumberg, PM (reprint author), NCI, Lab Canc Biol & Genet, Ctr Canc Res, Bldg 37,Room 4048B,37 Convent Dr,MSC 4255, Bethesda, MD 20892 USA.
EM blumberp@dc37a.nci.nih.gov
FU Intramural Research Program of the National Cancer Institute; Center for
Cancer Research [ZiA BC 005270, Z1A BC 005445]; NIH [GM28961]
FX Grant sponsor: Intramural Research Program of the National Cancer
Institute; Grant sponsor: Center for Cancer Research; Grant numbers: ZiA
BC 005270; Z1A BC 005445; Grant sponsor: NIH; Grant number: GM28961
NR 49
TC 1
Z9 1
U1 4
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0899-1987
EI 1098-2744
J9 MOL CARCINOGEN
JI Mol. Carcinog.
PD DEC
PY 2016
VL 55
IS 12
BP 2183
EP 2195
DI 10.1002/mc.22460
PG 13
WC Biochemistry & Molecular Biology; Oncology
SC Biochemistry & Molecular Biology; Oncology
GA EC1GY
UT WOS:000387854100024
PM 26859836
ER
PT J
AU Kimura, MY
Thomas, J
Tai, XG
Guinter, TI
Shinzawa, M
Etzensperger, R
Li, ZH
Love, P
Nakayama, T
Singer, A
AF Kimura, Motoko Y.
Thomas, Julien
Tai, Xuguang
Guinter, Terry I.
Shinzawa, Miho
Etzensperger, Ruth
Li, Zhenhu
Love, Paul
Nakayama, Toshinori
Singer, Alfred
TI Timing and duration of MHC I positive selection signals are adjusted in
the thymus to prevent lineage errors
SO NATURE IMMUNOLOGY
LA English
DT Article
ID T-CELL-RECEPTOR; TYROSINE KINASE; RUNX PROTEINS; CD4; THYMOCYTES;
DIFFERENTIATION; EXPRESSION; CHOICE; MOLECULES; ANTIGENS
AB Major histocompatibility complex class I (MHC I) positive selection of CD8(+) T cells in the thymus requires that T cell antigen receptor (TCR) signaling end in time for cytokines to induce Runx3d, the CD8-lineage transcription factor. We examined the time required for these events and found that the overall duration of positive selection was similar for all CD8(+) thymocytes in mice, despite markedly different TCR signaling times. Notably, prolonged TCR signaling times were counter-balanced by accelerated Runx3d induction by cytokines and accelerated differentiation into CD8(+) T cells. Consequently, lineage errors did not occur except when MHC I TCR signaling was so prolonged that the CD4-lineage-specifying transcription factor ThPOK was expressed, preventing Runx3d induction. Thus, our results identify a compensatory signaling mechanism that prevents lineage-fate errors by dynamically modulating Runx3d induction rates during MHC I positive selection.
C1 [Kimura, Motoko Y.; Thomas, Julien; Tai, Xuguang; Guinter, Terry I.; Shinzawa, Miho; Etzensperger, Ruth; Singer, Alfred] NCI, Expt Immunol Branch, NIH, Bldg 10, Bethesda, MD 20892 USA.
[Li, Zhenhu; Love, Paul] Eunice Kennedy Schriver Natl Inst Child Hlth & Hu, Lab Mammalian Genes & Dev, NIH, Bethesda, MD USA.
[Kimura, Motoko Y.; Nakayama, Toshinori] Chiba Univ, Dept Immunol, Chiba, Japan.
RP Kimura, MY; Singer, A (reprint author), NCI, Expt Immunol Branch, NIH, Bldg 10, Bethesda, MD 20892 USA.; Kimura, MY (reprint author), Chiba Univ, Dept Immunol, Chiba, Japan.
EM kimuramo@chiba-u.jp; singera@nih.gov
RI Nakayama, Toshinori/E-1067-2017
FU Intramural Research Program of the US National Institutes of Health,
National Cancer Institute, Center for Cancer Research; Ministry of
Education, Culture, Science and Technology [26893033, 15K08524]
FX We thank H. Park, D. Singer and N. Taylor for critical reading of the
manuscript; M. Nussenzweig (Rockefeller University) for
Rag2GFPTg mice; D. Littman (New York University) for
Runx3dYFP knock-in reporter mice; R. Bosselut (National
Cancer Institute) for ThpokGFP mice; M. Kubo (Tokyo
University of Science, Japan) for SOCS1Tg mice; and S.
Sharrow and L. Granger for flow cytometry. Supported by the Intramural
Research Program of the US National Institutes of Health, National
Cancer Institute, Center for Cancer Research, and the Ministry of
Education, Culture, Science and Technology (Grant-in-Aid for Research
Activity Start-up 26893033; and Scientific Research (C) 15K08524).
NR 42
TC 0
Z9 0
U1 5
U2 5
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1529-2908
EI 1529-2916
J9 NAT IMMUNOL
JI Nat. Immunol.
PD DEC
PY 2016
VL 17
IS 12
BP 1415
EP 1423
DI 10.1038/ni.3560
PG 9
WC Immunology
SC Immunology
GA EC3VY
UT WOS:000388056400012
PM 27668801
ER
PT J
AU Guitart, X
Bonaventura, J
Rea, W
Orru, M
Cellai, L
Dettori, I
Pedata, F
Brugarolas, M
Cortes, A
Casado, V
Chang, CP
Narayanan, M
Chern, Y
Ferre, S
AF Guitart, Xavier
Bonaventura, Jordi
Rea, William
Orru, Marco
Cellai, Lucrezia
Dettori, Ilaria
Pedata, Felicita
Brugarolas, Marc
Cortes, Antonio
Casado, Vicent
Chang, Ching-Pang
Narayanan, Manikandan
Chern, Yijuang
Ferre, Sergi
TI Equilibrative nucleoside transporter ENT1 as a biomarker of Huntington
disease
SO NEUROBIOLOGY OF DISEASE
LA English
DT Article
DE Adenosine; ENT1; A(2A) receptor; Huntington disease
ID ADENOSINE A(2A) RECEPTORS; A(1) RECEPTORS; RAT MODEL; EXPRESSION;
ASTROCYTES; DOPAMINE; BEHAVIOR; NEURONS; PROTEIN; BRAIN
AB The initial goal of this study was to investigate alterations in adenosine A(2A) receptor (A(2A)R) density or function in a rat model of Huntington disease (HD) with reported insensitivity to an A2AR antagonist. Unsuspected negative results led to the hypothesis of a low striatal adenosine tone and to the search for the mechanisms involved. Extracellular striatal concentrations of adenosine were measured with in vivo microdialysis in two rodent models of early neuropathological stages of HD disease, the Tg51 rat and the zQ175 knock-in mouse. In view of the crucial role of the equilibrative nucleoside transporter (ENTI) in determining extracellular content of adenosine, the binding properties of the ENT1 inhibitor [H-3]-S-(4-Nitrobenzyl)-6-thioinosine were evaluated in zQ175 mice and the differential expression and differential coexpression patterns of the ENT1 gene (SLC29A1) were analyzed in a large human cohort of HD disease and controls. Extracellular striatal levels of adenosine were significantly lower in both animal models as compared with control littermates and striatal ENTI binding sites were significantly upregulated in zQl 75 mice. ENT1 transcript was significantly upregulated in HD disease patients at an early neuropathological severity stage, but not those with a higher severity stage, relative to non-demented controls. ENTI transcript was differentially coexpressed (gained correlations) with several other genes in HD disease subjects compared to the control group. The present study demonstrates that ENTI and adenosine constitute biomarkers of the initial stages of neurodegeneration in HD disease and also predicts that ENT1 could constitute a new therapeutic target to delay the progression of the disease. Published by Elsevier Inc.
C1 [Guitart, Xavier; Bonaventura, Jordi; Rea, William; Orru, Marco; Ferre, Sergi] NIDA, Integrat Neurobiol Sect, Intramural Res Program, NIH, Triad Technol Bldg,333 Cassell Dr, Baltimore, MD 21224 USA.
[Cellai, Lucrezia; Dettori, Ilaria; Pedata, Felicita] Univ Florence, Div Pharmacol & Toxicol, Dept NEUROFARBA, I-50139 Florence, Italy.
[Brugarolas, Marc; Cortes, Antonio; Casado, Vicent] Univ Barcelona, Fac Biol, Dept Biochem & Mol Biol, E-08028 Barcelona, Spain.
[Brugarolas, Marc; Cortes, Antonio; Casado, Vicent] Ctr Biomed Res Neurodegenerat Dis Network, Barcelona 08028, Spain.
[Brugarolas, Marc; Cortes, Antonio; Casado, Vicent] Inst Biomed, Barcelona 08028, Spain.
[Chang, Ching-Pang; Chern, Yijuang] Acad Sinica, Div Neurosci, Inst Biomed Sci, Taipei 11529, Taiwan.
[Narayanan, Manikandan] NIAID, Syst Genom & Bioinformat Unit, Lab Syst Biol, Intramural Res Program,NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
RP Ferre, S (reprint author), NIDA, Integrat Neurobiol Sect, Intramural Res Program, NIH, Triad Technol Bldg,333 Cassell Dr, Baltimore, MD 21224 USA.
EM sferre@intra.nida.nih.gov
RI Ferre, Sergi/K-6115-2014;
OI Ferre, Sergi/0000-0002-1747-1779; Chern, Yijuang/0000-0002-5842-5429
FU NIDA; NIAID; CHDI Foundation [A-6703]
FX We thank Dr. Ling-Hui Li for the assistance in data extraction from the
GEO database and statistical analyses and Dr. Alessia Melani for her
assistance in the microdialysis experiments. Work supported by the
Intramural Funds of NIDA and NIAID, and from CHDI Foundation (grant
A-6703).
NR 43
TC 2
Z9 2
U1 4
U2 4
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0969-9961
EI 1095-953X
J9 NEUROBIOL DIS
JI Neurobiol. Dis.
PD DEC
PY 2016
VL 96
BP 47
EP 53
DI 10.1016/j.nbd.2016.08.013
PG 7
WC Neurosciences
SC Neurosciences & Neurology
GA EC3WX
UT WOS:000388058900006
PM 27567601
ER
PT J
AU Juczewski, K
von Richthofen, H
Bagni, C
Celikel, T
Fisone, G
Krieger, P
AF Juczewski, Konrad
von Richthofen, Helen
Bagni, Claudia
Celikel, Tansu
Fisone, Gilberto
Krieger, Patrik
TI Somatosensory map expansion and altered processing of tactile inputs in
a mouse model of fragile X syndrome
SO NEUROBIOLOGY OF DISEASE
LA English
DT Article
DE Fragile X syndrome; Barrel cortex; Sensory processing; Hyperexcitation;
In vivo electrophysiology; Fmr1 KO; Whisker system; Gap-crossing task;
FMRP; Behavior
ID MENTAL-RETARDATION PROTEIN; EXPERIENCE-DEPENDENT PLASTICITY; RAT BARREL
CORTEX; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; RECEPTIVE-FIELD
PROPERTIES; KNOCK-OUT MICE; SYNAPTIC PLASTICITY; LAYER-IV; HOMEOSTATIC
PLASTICITY; SENSORIMOTOR SYSTEM
AB Fragile X syndrome (FXS) is a common inherited form of intellectual disability caused by the absence or reduction of the fragile X mental retardation protein (FMRP) encoded by the FMR1 gene. In humans, one symptom of FXS is hypersensitivity to sensory stimuli, including touch. We used a mouse model of FXS (Fmr1 KO) to study sensory processing of tactile information conveyed via the whisker system. In vivo electrophysiological recordings in somatosensory barrel cortex showed layer-specific broadening of the receptive fields at the level of layer 2/3 but not layer 4, in response to whisker stimulation. Furthermore, the encoding of tactile stimuli at different frequencies was severely affected in layer 2/3. The behavioral effect of this broadening of the receptive fields was tested in the gap-crossing task, a whisker-dependent behavioral paradigm. In this task the Fmr1 KO mice showed differences in the number of whisker contacts with platforms, decrease in the whisker sampling duration and reduction in the whisker touch-time while performing the task. We propose that the increased excitability in the somatosensory barrel cortex upon whisker stimulation may contribute to changes in the whisking strategy as well as to other observed behavioral phenotypes related to tactile processing in Fmr1 KO mice. (C) 2016 Elsevier Inc. All rights reserved.
C1 [Juczewski, Konrad; von Richthofen, Helen; Fisone, Gilberto] Karolinska Inst, Dept Neurosci, Stockholm, Sweden.
[Bagni, Claudia] Katholieke Univ Leuven, VIB Ctr Biol Dis, Leuven, Belgium.
[Bagni, Claudia] Univ Roma Tor Vergata, Dept Biomed & Prevent, Rome, Italy.
[Celikel, Tansu] Radboud Univ Nijmegen, Donders Inst Brain Cognit & Behav, Dept Neurophysiol, Nijmegen, Netherlands.
[Krieger, Patrik] Ruhr Univ Bochum, Fac Med, Dept Syst Neurosci, Bochum, Germany.
[Bagni, Claudia] Univ Lausanne, Dept Fundamental Neurosci, Lausanne, Switzerland.
RP Juczewski, K (reprint author), NIAAA, NIH, 5625 Fishers Lane, Rockville, MD 20852 USA.; Krieger, P (reprint author), Ruhr Univ Bochum, Dept Syst Neurosci, Univ Str 150, D-44801 Bochum, Germany.
EM konrad.juczewski@nih.gov; patrik.krieger@rub.de
FU Karolinska Institutet-National Institutes of Health [88/10-607]; FWO
[G088415N]; Telethon [GGP15257]; Swedish Research Council [13482]
FX This research was supported by Karolinska Institutet-National Institutes
of Health (grant number 88/10-607); FWO (grant number G088415N) and
Telethon (grant number GGP15257) to CB; Swedish Research Council (grant
number 13482) to GF. The authors declare no competing financial
interests.
NR 130
TC 1
Z9 1
U1 6
U2 6
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0969-9961
EI 1095-953X
J9 NEUROBIOL DIS
JI Neurobiol. Dis.
PD DEC
PY 2016
VL 96
BP 201
EP 215
DI 10.1016/j.nbd.2016.09.007
PG 15
WC Neurosciences
SC Neurosciences & Neurology
GA EC3WX
UT WOS:000388058900019
PM 27616423
ER
PT J
AU Yang, LY
Greig, NH
Huang, YN
Hsieh, TH
Tweedie, D
Yu, QS
Hoffer, BJ
Luo, Y
Kao, YC
Wang, JY
AF Yang, Ling-Yu
Greig, Nigel H.
Huang, Ya-Ni
Hsieh, Tsung-Hsun
Tweedie, David
Yu, Qian-Sheng
Hoffer, Barry J.
Luo, Yu
Kao, Yu-Chieh
Wang, Jia-Yi
TI Post-traumatic administration of the p53 inactivator pifithrin-alpha,
oxygen analogue reduces hippocampal neuronal loss and improves cognitive
deficits after experimental traumatic brain injury
SO NEUROBIOLOGY OF DISEASE
LA English
DT Article
DE Traumatic brain injury (TBI); p53; Pifithrin-alpha (PFT-alpha);
PFT-alpha oxygen analogue (PFT-alpha (o)); Apoptosis; Motor and
cognitive deficits; Puma; Controlled cortical impact (CCI)
ID FLUORO-JADE-C; PEPTIDE-1 RECEPTOR AGONIST; TUMOR-SUPPRESSOR GENE;
NF-KAPPA-B; CELL-DEATH; DEGENERATING NEURONS; FUNCTIONAL OUTCOMES;
UNITED-STATES; UP-REGULATION; HEAD-INJURY
AB Traumatic brain injury (TBI) is a major cause of death and disability worldwide. Neuronal apoptosis in the hippo campus has been detected after TBI. The hippocampal dysfunction may result in cognitive deficits in learning, memory, and spatial information processing. Our previous studies demonstrated that a p53 inhibitor, pifithrin-alpha oxygen analogue (PFT-alpha (O)), significantly reduced cortical cell death, which is substantial following controlled cortical impact (CCI) TBI, and improved neurological functional outcomes via anti-apoptotic mechanisms. In the present study, we examined the effect of PFT-alpha (O) on CCI TBI-induced hippocampal cellular pathophysiology in light of this brain region's role in memory. To investigate whether p53-dependent apoptosis plays a role in hippocampal neuronal loss and associated cognitive deficits and to define underlying mechanisms, SD rats were subjected to experimental CCI TBI followed by the administration of PFT-alpha or PFT-alpha (O) (2 mg/kg, i.v.) or vehicle at 5 h after TBI. Magnetic resonance imaging (MRI) scans were acquired at 24 h and 7 days post-injury to assess evolving structural hippocampal damage. Fluoro-Jade C was used to stain hippocampal sub-regions, including CA1 and dentate gyrus (DG), for cellular degeneration. Neurological functions, including motor and recognition memory, were assessed by behavioral tests at 7 days post injury. p53, p53 upregulated modulator of apoptosis (PUMA), 4-hydroxynonenal (4-HNE), cyclooxygenase-IV (COX IV), annexin V and NeuN were visualized by double immunofluorescence staining with cell-specific markers. Levels of mRNA encoding for caspase-3, p53, PUMA, Bcl-2, Bcl-2-associated X protein (BAX) and superoxide dismutase (SOD) were measured by RT-qPCR. Our results showed that post-injury administration of PFT-alpha and, particularly, PFT-alpha (O) at 5 h dramatically reduced injury volumes in the ipsilateral hippocampus, improved motor outcomes, and ameliorated cognitive deficits at 7 days after TBI, as evaluated by novel object recognition and open-field test. PFT-alpha and especially PFT-alpha (O) significantly reduced the number of FJC-positive cells in hippocampus CA1 and DG subregions, versus vehicle treatment, and significantly decreased caspase-3 and PUMA mRNA expression. PFT-alpha (O), but not PFT-alpha, treatment significantly lowered p53 and elevated SOD2 mRNA expression. Double immunofluorescence staining demonstrated that PFT-alpha (O) treatment decreased p53, annexin V and 4-HNE positive neurons in the hippocampal CA1 region. Furthermore, PUMA co-localization with the mitochondrial maker COX IV, and the upregulation of PUMA were inhibited by PFT-alpha (O) after TBI. Our data suggest that PFT-alpha and especially PFT-alpha (O) significantly reduce hippocampal neuronal degeneration, and ameliorate neurological and cognitive deficits in vivo via antiapoptotic and antioxidative properties. (C) 2016 Published by Elsevier Inc.
C1 [Yang, Ling-Yu; Huang, Ya-Ni; Wang, Jia-Yi] Taipei Med Univ, Grad Inst Med Sci, Coll Med, 250 Wu Hsing St, Taipei 110, Taiwan.
[Greig, Nigel H.; Tweedie, David; Yu, Qian-Sheng] NIA, Drug Design & Dev Sect, Translat Gerontol Branch, Intramural Res Program,NIH, Baltimore, MD 21224 USA.
[Huang, Ya-Ni] Hsin Sheng Jr Coll Med Care & Management, Dept Nursing, Taoyuan, Taiwan.
[Hsieh, Tsung-Hsun] Chang Gung Univ, Coll Med, Dept Phys Therapy, Taoyuan, Taiwan.
[Hsieh, Tsung-Hsun] Chang Gung Univ, Coll Med, Grad Inst Rehabil Sci, Taoyuan, Taiwan.
[Hsieh, Tsung-Hsun] Taipei Med Univ, Grad Inst Neural Regenerat Med, Taipei, Taiwan.
[Hoffer, Barry J.; Luo, Yu] Case Western Reserve Univ, Sch Med, Dept Neurosurg, Cleveland, OH USA.
[Kao, Yu-Chieh] Taipei Med Univ, Sch Med, Translat Imaging Res Ctr, Taipei, Taiwan.
[Kao, Yu-Chieh] Taipei Med Univ, Sch Med, Dept Radiol, Taipei, Taiwan.
[Wang, Jia-Yi] Taipei Med Univ, Sch Med, Dept Physiol, Coll Med, Taipei, Taiwan.
RP Wang, JY (reprint author), Taipei Med Univ, Grad Inst Med Sci, Coll Med, 250 Wu Hsing St, Taipei 110, Taiwan.
EM jywang2010@tmu.edu.tw
FU Ministry of Science and Technology [MOST104-2923-B-038-001-MY3 (1-3
2-3)]; National Institutes of Health NINDS [R01NS094152]; Intramural
Research Program, National Institute on Aging, National Institutes of
Health NINDS, USA [R01NS094152]
FX This study was supported in part by grants from (i) the Ministry of
Science and Technology (MOST104-2923-B-038-001-MY3 (1-3 & 2-3) (ii)
National Institutes of Health NINDS grant R01NS094152 and by (iii) the
Intramural Research Program, National Institute on Aging, National
Institutes of Health NINDS grant R01NS094152, USA. The authors thank the
Translational Imaging Research Center at Taipei Medical University for
technical support in relation to animal setup and MRI imaging. For
information relating to PFT-alpha. (O) contact NHG 22. In a double-blind, between-groups trial, 31 "restrained" eaters were stabilized on either pexacerfont (300 mg/day for 7 days, then 100 mg/day for 21 days) or placebo. On day 15, they underwent a math-test stressor; during three subsequent visits, they heard personalized craving-induction scripts. In each session, stress-induced food consumption and craving were assessed in a bogus taste test and on visual analog scales. We used digital video to monitor daily ingestion of study capsules and nightly rating of food problems/preoccupation on the Yale Food Addiction Scale (YFAS).
The study was stopped early due to an administrative interpretation of US federal law, unrelated to safety or outcome. The bogus taste tests suggested some protective effect of pexacerfont against eating after a laboratory stressor (r (effect) = 0.30, 95 % CL = -0.12, 0.63, Bayes factor 11.30). Similarly, nightly YFAS ratings were lower with pexacerfont than placebo (r (effect) = 0.39, CI 0.03, 0.66), but this effect should be interpreted with caution because it was present from the first night of pill ingestion, despite pexacerfont's slow pharmacokinetics.
The findings may support further investigation of the anticraving properties of CRF1 antagonists, especially for food.
C1 [Epstein, David H.; Kennedy, Ashley P.; Furnari, Melody; Heilig, Markus; Shaham, Yavin; Phillips, Karran A.; Preston, Kenzie L.] NIDA, Intramural Res Program, NIH, 251 Bayview Blvd,BRC Bldg,Suite 200, Baltimore, MD 21224 USA.
RP Epstein, DH (reprint author), NIDA, Intramural Res Program, NIH, 251 Bayview Blvd,BRC Bldg,Suite 200, Baltimore, MD 21224 USA.
EM depstein@intra.nida.nih.gov
FU NIDA Intramural Research Program
FX This study was funded by the NIDA Intramural Research Program.
Pexacerfont and placebo capsules were obtained from Bristol-Meyers
Squibb (BMS), under an agreement that permitted either BMS or the
investigators to publish the results after giving the other party 60
days to check for disclosure of confidential information. BMS had no
input into the drafting of this paper and requested no changes.
NR 45
TC 0
Z9 0
U1 7
U2 7
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0033-3158
EI 1432-2072
J9 PSYCHOPHARMACOLOGY
JI Psychopharmacology
PD DEC
PY 2016
VL 233
IS 23-24
BP 3921
EP 3932
DI 10.1007/s00213-016-4424-5
PG 12
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA EB8RW
UT WOS:000387659500009
PM 27595147
ER
PT J
AU Secci, ME
Factor, JA
Schindler, CW
Panlilio, LV
AF Secci, Maria E.
Factor, Julie A.
Schindler, Charles W.
Panlilio, Leigh V.
TI Choice between delayed food and immediate oxycodone in rats
SO PSYCHOPHARMACOLOGY
LA English
DT Article
DE Addiction; Animal models; Behavioral economics; Concurrent choice; Delay
discounting; Impulsivity
ID RHESUS-MONKEYS; DRUG-USE; COCAINE; HEROIN; REINFORCEMENT; REWARD;
IMPULSIVITY; ADDICTION; NALOXONE; BEHAVIOR
AB The choice to seek immediate drug effects instead of more meaningful but delayed rewards is a defining feature of addiction.
To develop a rodent model of this behavior, we allowed rats to choose between immediate intravenous delivery of the prescription opioid oxycodone (50 mu g/kg) and delayed delivery of palatable food pellets.
Rats preferred food at delays up to 30 s, but they chose oxycodone and food equally at 60-s delay and preferred oxycodone over food at 120-s delay. Comparison of food-drug choice, food-only, and drug-only conditions indicated that food availability decreased drug intake, but drug availability increased food intake. In the food-only condition, food was effective as a reinforcer even when delayed by 120 s. Pre-session feeding with chow slowed acquisition of food and drug self-administration, but did not affect choice. To establish procedures for testing potential anti-addiction medications, noncontingent pre-treatment with oxycodone or naltrexone (analogous to substitution and antagonist therapies, respectively) were tested on a baseline in which oxycodone was preferred over delayed food. Naltrexone pre-treatment decreased drug intake and increased food intake. Oxycodone pre-treatment decreased drug intake, but also produced extended periods with no food or drug responding.
These findings show that the contingencies that induce preference for drugs over more meaningful but less immediate rewards in humans can be modeled in rodents, and they suggest that the model could be useful for assessing the therapeutic potential of treatments and exploring the underlying behavioral and neural mechanisms involved in addiction.
C1 [Secci, Maria E.; Factor, Julie A.; Schindler, Charles W.; Panlilio, Leigh V.] NIDA, Preclin Pharmacol Sect, Behav Neurosci Branch, Intramural Res Programl,NIH,US Dept HHS, 251 Bayview Blvd, Baltimore, MD 21224 USA.
RP Panlilio, LV (reprint author), NIDA, Preclin Pharmacol Sect, Behav Neurosci Branch, Intramural Res Programl,NIH,US Dept HHS, 251 Bayview Blvd, Baltimore, MD 21224 USA.
EM lpanlili@intra.nida.nih.gov
FU Intramural Research Program of the NIH, National Institute on Drug Abuse
FX This research was supported by the Intramural Research Program of the
NIH, National Institute on Drug Abuse. Thanks to Yavin Shaham for
invaluable suggestions during planning of the study and preparation of
the manuscript.
NR 50
TC 0
Z9 0
U1 4
U2 4
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0033-3158
EI 1432-2072
J9 PSYCHOPHARMACOLOGY
JI Psychopharmacology
PD DEC
PY 2016
VL 233
IS 23-24
BP 3977
EP 3989
DI 10.1007/s00213-016-4429-0
PG 13
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA EB8RW
UT WOS:000387659500014
PM 27678551
ER
PT J
AU Ito, Y
Clary, R
AF Ito, Yoichiro
Clary, Robert
TI Comparison in Partition Efficiency of Protein Separation between Four
Different Tubing Modifications in Spiral High-Speed Countercurrent
Chromatography
SO SEPARATIONS
LA English
DT Article
DE spiral high-speed countercurrent chromatography; tubing shape
modification; protein separation; polymer phase system
ID SUPPORT
AB High-speed countercurrent chromatography with a spiral tube assembly can retain a satisfactory amount of stationary phase of polymer phase systems used for protein separation. In order to improve the partition efficiency, a simple tool was fabricated to modify the tubing shapes, and the following four different tubing modifications were made: intermittently pressed at 10 mm width, flat, flat-wave, and flat-twist. Partition efficiencies of the separation column made from these modified tubings were examined in protein separation with an aqueous-aqueous polymer phase system at flow rates of 1-2 mL/min under 800 rpm. The results indicated that the column with all modified tubing improved the partition efficiency at a flow rate of 1 mL/min, but at a higher flow rate of 2 mL/min, the columns made of flattened tubing showed lowered partition efficiency, apparently due to the loss of the retained stationary phase. Among all the modified columns, the column with intermittently pressed tubing gave the best peak resolution. It may be concluded that the intermittently pressed and flat-twist improve the partition efficiency in a semi-preparative separation, while other modified tubing of flat and flat-wave configurations may be used for analytical separations with a low flow rate.
C1 [Ito, Yoichiro] NHLBI, Lab Bioseparat Technol, Biochem & Biophys Ctr, NIH, Bethesda, MD 20892 USA.
[Clary, Robert] NIH, Machine Instrumentat Design & Fabricat, Bethesda, MD 20892 USA.
RP Ito, Y (reprint author), NHLBI, Lab Bioseparat Technol, Biochem & Biophys Ctr, NIH, Bethesda, MD 20892 USA.
EM itoy2@mail.nih.gov; claryrob@od.nih.gov
NR 17
TC 0
Z9 0
U1 3
U2 3
PU MDPI AG
PI BASEL
PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND
SN 2297-8739
EI 2227-9075
J9 SEPARATIONS
JI Separations
PD DEC
PY 2016
VL 3
IS 4
AR 31
DI 10.3390/separations3040031
PG 7
WC Chemistry, Analytical
SC Chemistry
GA EC2MQ
UT WOS:000387955900004
ER
PT J
AU Shinomiya, K
Zaima, K
Harikai, N
Ito, Y
AF Shinomiya, Kazufusa
Zaima, Kazumasa
Harikai, Naoki
Ito, Yoichiro
TI Improved Separations of Proteins and Sugar Derivatives Using the
Small-Scale Cross-Axis Coil Planet Centrifuge with Locular Multilayer
Coiled Columns
SO SEPARATIONS
LA English
DT Article
DE countercurrent chromatography; cross-axis coil planet centrifuge;
locular multilayer coil; partition efficiency; proteins;
4-methylumbelliferyl sugar derivatives
ID POLYMER PHASE SYSTEMS; PREPARATIVE COUNTERCURRENT CHROMATOGRAPHY;
PARTITION EFFICIENCY; TUBING MODIFICATIONS; STATIONARY-PHASE; ROTARY
SEALS; APPARATUS; ASSEMBLIES; RETENTION; DESIGN
AB (1) Background: Countercurrent chromatography (CCC) is liquid-liquid partition chromatography without using a solid support matrix. This technique requires further improvement of peak resolution and shortening of separation time. (2) Methods: The long-pressed locular multilayer coils with and without mixer glass beads were developed for the separation of proteins and 4-methylumbelliferyl sugar derivatives using a small-scale cross-axis coil planet centrifuge. (3) Results: Proteins were separated from each other and the separation was improved when the flow rate of the mobile phase was decreased from 0.8 to 0.4 mL/min. On the other hand, 4-methylumbelliferyl sugar derivatives were separated at the resolution of almost over 1.5 in short separation time under satisfactory stationary phase retention when the flow rate of the mobile phase was increased from 1.0 to 1.4 mL/min. (4) Conclusion: Better peak resolutions over the previous results were achieved using the long-pressed locular multilayer coil for proteins with aqueous two-phase systems (ATPS) and for 4-methylumbelliferyl sugar derivatives with organic-aqueous two-phase solvent systems by inserting a glass bead into each locule.
C1 [Shinomiya, Kazufusa; Zaima, Kazumasa; Harikai, Naoki] Nihon Univ, Sch Pharm, 7-7-1,Narashinodai, Funabashi, Chiba 2748555, Japan.
[Ito, Yoichiro] NHLBI, Lab Bioseparat Technol, Biochem & Biophys Ctr, NIH, 10 Ctr Dr,Bldg 10,Room 8N230, Bethesda, MD 20892 USA.
RP Shinomiya, K (reprint author), Nihon Univ, Sch Pharm, 7-7-1,Narashinodai, Funabashi, Chiba 2748555, Japan.
EM shinomiya.kazufusa@nihon-u.ac.jp; zaima.kazumasa@nihon-u.ac.jp;
harikai.naoki@nihon-u.ac.jp; itoy@nhlbi.nih.gov
NR 18
TC 0
Z9 0
U1 4
U2 4
PU MDPI AG
PI BASEL
PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND
SN 2297-8739
EI 2227-9075
J9 SEPARATIONS
JI Separations
PD DEC
PY 2016
VL 3
IS 4
AR 29
DI 10.3390/separations3040029
PG 10
WC Chemistry, Analytical
SC Chemistry
GA EC2MQ
UT WOS:000387955900002
ER
PT J
AU Yang, Z
Holt, HK
Fan, JH
Ma, L
Liu, Y
Chen, W
Como, P
Zhang, L
Qiao, YL
AF Yang, Zhao
Holt, Hunter K.
Fan, Jin-Hu
Ma, Li
Liu, Ying
Chen, Wen
Como, Peter
Zhang, Lin
Qiao, You-Lin
TI Optimal Cutoff Scores for Alzheimer's Disease Using the Chinese Version
of Mini-Mental State Examination Among Chinese Population Living in
Rural Areas
SO AMERICAN JOURNAL OF ALZHEIMERS DISEASE AND OTHER DEMENTIAS
LA English
DT Article
DE Alzheimer's disease; Chinese version Mini-Mental State Examination;
Chinese population; cutoff scores; rural areas; ROC analysis
ID MILD COGNITIVE IMPAIRMENT; GENERAL-POPULATION; CANCER INCIDENCE;
DEMENTIA; LINXIAN; DIAGNOSIS; EDUCATION; HEALTH; SUPPLEMENTATION;
PREVALENCE
AB To explore the optimal cutoff score for initial detection of Alzheimer's Disease (AD) through the Chinese version of Mini-Mental State Examination (CMMSE) in rural areas in China, we conducted a cross-sectional study within the Linxian General Population Nutritional Follow-up study. 16,488 eligible cohort members participated in the survey and 881 completed the CMMSE. Among 881 participants, the median age (Interquartile range) was 69.00 (10.00), 634 (71.92%) were female, 657 (74.57%) were illiterate, 35 (3.97%) had 6 years of education or higher, and 295 (33.48%) were diagnosed with AD. By reducing the CMMSE criteria for illiterate to 16 points, primary school to 19 points, and middle school or higher to 23 points, the efficiency of Chinese version of Mini-Mental State Examination can be significantly improved for initial detection of AD in rural areas in China, especially in those nutrition deficient areas.
C1 [Yang, Zhao; Fan, Jin-Hu; Chen, Wen; Qiao, You-Lin] Chinese Acad Med Sci, Canc Hosp Inst, Dept Canc Epidemiol, Beijing, Peoples R China.
[Yang, Zhao; Fan, Jin-Hu; Chen, Wen; Qiao, You-Lin] Peking Union Med Coll, Beijing, Peoples R China.
[Holt, Hunter K.] Rush Univ, Coll Med, Dept Family Med, Chicago, IL 60612 USA.
[Holt, Hunter K.] NIH, Fogarty Int Ctr, Bldg 10, Bethesda, MD 20892 USA.
[Ma, Li] Dalian Med Univ, Dept Epidemiol, Dalian, Peoples R China.
[Liu, Ying] Second Affiliated Hosp Dalian, Dept Neurol, Dalian, Peoples R China.
[Como, Peter] US FDA, Silver Spring, MD USA.
[Zhang, Lin] Univ Calif Davis, Dept Neurol, Davis, CA 95616 USA.
RP Fan, JH (reprint author), Chinese Acad Med Sci, Canc Hosp Inst, Dept Canc Epidemiol, Beijing, Peoples R China.; Fan, JH (reprint author), Peking Union Med Coll, Beijing, Peoples R China.; Ma, L (reprint author), Dalian Med Univ, Dept Epidemiol, Dalian, Peoples R China.
EM fanjh@cicams.ac.cn; mali_lele@sina.com
FU NIH [NHHSN261200477001C]; Cancer Institute of the Chinese Academy of
Medical Sciences; China National Natural Science Foundation [81200989];
Chinese Academy of Medical Sciences; Intramural Research Program of the
US National Cancer Institute, NIH; NIH Fogarty International Center
Grant [5R25TW009340]
FX This study was supported in part by NIH contract NHHSN261200477001C with
the Cancer Institute of the Chinese Academy of Medical Sciences; by
funds from the China National Natural Science Foundation No. 81200989;
by additional funds from the Chinese Academy of Medical Sciences; by
funds from the Intramural Research Program of the US National Cancer
Institute, NIH and finally, funds from the NIH Fogarty International
Center Grant #5R25TW009340.
NR 44
TC 0
Z9 0
U1 3
U2 3
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1533-3175
EI 1938-2731
J9 AM J ALZHEIMERS DIS
JI Am. J. Alzheimers Dis. Other Dement.
PD DEC
PY 2016
VL 31
IS 8
BP 650
EP 657
DI 10.1177/1533317516662336
PG 8
WC Geriatrics & Gerontology; Clinical Neurology
SC Geriatrics & Gerontology; Neurosciences & Neurology
GA EB6IP
UT WOS:000387485900006
PM 27659393
ER
PT J
AU Dickens, C
Pfeiffer, RM
Anderson, WF
Duarte, R
Kellett, P
Schuz, J
Kielkowski, D
McCormack, VA
AF Dickens, Caroline
Pfeiffer, Ruth M.
Anderson, William F.
Duarte, Raquel
Kellett, Patricia
Schuz, Joachim
Kielkowski, Danuta
McCormack, Valerie A.
TI Investigation of breast cancer sub-populations in black and white women
in South Africa
SO BREAST CANCER RESEARCH AND TREATMENT
LA English
DT Article
DE Breast cancer; Receptors; Age distributions; South Africa
ID UNITED-STATES; RISK-FACTORS; TRENDS; AGE; HETEROGENEITY; PREVALENCE;
CARCINOMA; DIAGNOSIS; PATTERNS; ESTROGEN
AB Bimodal age distributions at diagnosis have been widely observed among US and European female breast cancer populations. To determine whether bimodal breast cancer distributions are also present in a sub-Saharan African population, we investigated female breast cancer in South Africa.
Using the South African National Cancer Registry data, we examined age-at-diagnosis frequency distributions (density plots) for breast cancer overall and by their receptor (oestrogen, progesterone and HER2) determinants among black and white women diagnosed during 2009-2011 in the public healthcare sector. For comparison, we also analysed corresponding 2010-2011 US SEER data. We investigated density plots using flexible mixture models, allowing early/late-onset membership to depend on receptor status.
We included 8857 women from South Africa, 7176 (81 %) with known oestrogen receptor status, and 95064 US women. Bimodality was present in all races, with an early-onset mode between ages 40-50 years and a late-onset mode among ages 60-70 years. The early-onset mode was younger in South African black women (age 38), compared to other groups (45-54 years).
Consistent patterns of bimodality and of its receptor determinants were present across breast cancer patient populations in South Africa and the US. Although the clinical spectrum of breast cancer is well acknowledged as heterogeneous, universal early- and late-onset age distributions at diagnosis suggest that breast cancer etiology consists of a mixture two main types.
C1 [Dickens, Caroline; Schuz, Joachim; McCormack, Valerie A.] Int Agcy Res Canc, Sect Environm & Radiat, Lyon, France.
[Dickens, Caroline; Duarte, Raquel] Univ Witwatersrand, Dept Internal Med, Fac Hlth Sci, 7 York Rd, ZA-2193 Johannesburg, South Africa.
[Pfeiffer, Ruth M.; Anderson, William F.] NCI, Div Canc Epidemiol & Genet, Biostat Branch, Execut Plaza South Rm 8036,6120 Execut Blvd, Bethesda, MD 20892 USA.
[Kellett, Patricia; Kielkowski, Danuta] Natl Canc Registry South Africa, Natl Hlth & Lab Serv, Johannesburg, South Africa.
RP Dickens, C (reprint author), Int Agcy Res Canc, Sect Environm & Radiat, Lyon, France.; Dickens, C (reprint author), Univ Witwatersrand, Dept Internal Med, Fac Hlth Sci, 7 York Rd, ZA-2193 Johannesburg, South Africa.
EM caroline.dickens@wits.ac.za
FU International Agency for Research on Cancer; European Commission FP7
Marie Curie Actions - People - Co-funding of regional, national and
international programmes (COFUND)
FX The work reported in this paper was undertaken during the tenure of a
Postdoctoral Fellowship to Dr Dickens from the International Agency for
Research on Cancer, partially supported by the European Commission FP7
Marie Curie Actions - People - Co-funding of regional, national and
international programmes (COFUND).
NR 24
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U1 5
U2 5
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0167-6806
EI 1573-7217
J9 BREAST CANCER RES TR
JI Breast Cancer Res. Treat.
PD DEC
PY 2016
VL 160
IS 3
BP 531
EP 537
DI 10.1007/s10549-016-4019-1
PG 7
WC Oncology
SC Oncology
GA EB4LH
UT WOS:000387342800013
PM 27757717
ER
PT J
AU Neuhouser, ML
Smith, AW
George, SM
Gibson, JT
Baumgartner, KB
Baumgartner, R
Duggan, C
Bernstein, L
McTiernan, A
Ballard, R
AF Neuhouser, Marian L.
Smith, Ashley Wilder
George, Stephanie M.
Gibson, James T.
Baumgartner, Kathy B.
Baumgartner, Richard
Duggan, Catherine
Bernstein, Leslie
McTiernan, Anne
Ballard, Rachel
TI Use of complementary and alternative medicine and breast cancer survival
in the Health, Eating, Activity, and Lifestyle Study
SO BREAST CANCER RESEARCH AND TREATMENT
LA English
DT Article
DE Breast cancer; Complementary and alternative medicine; Cancer
survivorship; Mortality
ID ESTROGENIC BOTANICAL SUPPLEMENTS; QUALITY-OF-LIFE; PROSPECTIVE COHORT;
PHYSICAL-ACTIVITY; PROSTATE-CANCER; WOMEN; THERAPY; TRIAL; DIET; SOY
AB Use of complementary and alternative medicine (CAM) is common among breast cancer patients, but less is known about whether CAM influences breast cancer survival.
Health Eating, Activity, and Lifestyle (HEAL) Study participants (n = 707) were diagnosed with stage I-IIIA breast cancer. Participants completed a 30-month post-diagnosis interview including questions on CAM use (natural products such as dietary and botanical supplements, alternative health practices, and alternative medical systems), weight, physical activity, and comorbidities. Outcomes were breast cancer-specific and total mortality, which were ascertained from the Surveillance Epidemiology and End Results registries in Western Washington, Los Angeles County, and New Mexico. Cox proportional hazards regression models were fit to data to estimate hazard ratios (HR) and 95 % confidence intervals (CI) for mortality. Models were adjusted for potential confounding by sociodemographic, health, and cancer-related factors.
Among 707 participants, 70 breast cancer-specific deaths and 149 total deaths were reported. 60.2 % of participants reported CAM use post-diagnosis. The most common CAM were natural products (51 %) including plant-based estrogenic supplements (42 %). Manipulative and body-based practices and alternative medical systems were used by 27 and 13 % of participants, respectively. No associations were observed between CAM use and breast cancer-specific (HR 1.04, 95 % CI 0.61-1.76) or total mortality (HR 0.91, 95 % CI 0.63-1.29).
Complementary and alternative medicine use was not associated with breast cancer-specific mortality or total mortality. Randomized controlled trials may be needed to definitively test whether there is harm or benefit from the types of CAM assessed in HEAL in relation to mortality outcomes in breast cancer survivors.
C1 [Neuhouser, Marian L.; Duggan, Catherine; McTiernan, Anne] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, 1100 Fairview Ave North,M4B402, Seattle, WA 98109 USA.
[Smith, Ashley Wilder] NCI, Outcomes Res Branch, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[George, Stephanie M.; Ballard, Rachel] NIH, Off Dis Prevent, Bldg 10, Bethesda, MD 20892 USA.
[Gibson, James T.] Informat Management Serv Inc, Calverton, MD USA.
[Baumgartner, Kathy B.; Baumgartner, Richard] Univ Louisville, James Graham Brown Canc Ctr, Dept Epidemiol & Populat Hlth, Louisville, KY 40292 USA.
[Bernstein, Leslie] Beckman Res Inst City Hope, Dept Populat Sci, Div Canc Etiol, Duarte, CA USA.
RP Neuhouser, ML (reprint author), Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, 1100 Fairview Ave North,M4B402, Seattle, WA 98109 USA.
EM mneuhous@fredhutch.org
FU National Cancer Institute [N01-CN-75036-20, N01-CN-05228, N01-PC-67010];
National Institutes of Health [M01-RR-00037]; University of New Mexico
NCRR [M01-RR-0997]; California Department of Health Services
[050Q-8709-S1528]
FX The HEAL study was funded by National Cancer Institute
(N01-CN-75036-20), N01-CN-05228, N01-PC-67010, National Institutes of
Health M01-RR-00037), University of New Mexico NCRR M01-RR-0997,
California Department of Health Services 050Q-8709-S1528.
NR 48
TC 0
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U1 42
U2 42
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0167-6806
EI 1573-7217
J9 BREAST CANCER RES TR
JI Breast Cancer Res. Treat.
PD DEC
PY 2016
VL 160
IS 3
BP 539
EP 546
DI 10.1007/s10549-016-4010-x
PG 8
WC Oncology
SC Oncology
GA EB4LH
UT WOS:000387342800014
PM 27766453
ER
PT J
AU Wang, W
Erbe, AK
Gallenberger, M
Kim, K
Carmichael, L
Hess, D
Mendonca, EA
Song, YQ
Hank, JA
Cheng, SC
Signoretti, S
Atkins, M
Carlson, A
Weiss, JM
Mier, J
Panka, D
McDermott, DF
Sondel, PM
AF Wang, Wei
Erbe, Amy K.
Gallenberger, Mikayla
Kim, KyungMann
Carmichael, Lakeesha
Hess, Dustin
Mendonca, Eneida A.
Song, Yiqiang
Hank, Jacquelyn A.
Cheng, Su-Chun
Signoretti, Sabina
Atkins, Michael
Carlson, Alexander
Weiss, Jonathan M.
Mier, James
Panka, David
McDermott, David F.
Sondel, Paul M.
TI Killer immunoglobulin-like receptor (KIR) and KIR-ligand genotype do not
correlate with clinical outcome of renal cell carcinoma patients
receiving high-dose IL2
SO CANCER IMMUNOLOGY IMMUNOTHERAPY
LA English
DT Article
DE Renal cell carcinoma; High-dose IL2; Killer immunoglobulin-like
receptors; HLA; NK cells
ID ACUTE MYELOGENOUS LEUKEMIA; UNLICENSED NK CELLS; RECOMBINANT
INTERLEUKIN-2; HLA-C; UNRELATED TRANSPLANTATION; NEUROBLASTOMA PATIENTS;
IN-VITRO; ANTIBODY; MISMATCH; TUMOR
AB NK cells play a role in many cancer immunotherapies. NK cell activity is tightly regulated by killer immunoglobulin-like receptor (KIR) and KIR-ligand interactions. Inhibitory KIR-ligands have been identified as HLA molecules, while activating KIR-ligands are largely unknown. Individuals that have not inherited the corresponding KIR-ligand for at least one inhibitory KIR gene are termed the "KIR-ligand missing" genotype, and they are thought to have a subset of NK cells that express inhibitory KIRs for which the corresponding KIR-ligand is missing on autologous tissue, and thus will not be inhibited through KIR-ligand recognition. In some settings where an anticancer immunotherapeutic effect is likely mediated by NK cells, individuals with a KIR-ligand missing genotype have shown improved clinical outcome compared to individuals with an "all KIR-ligands present" genotype. In addition, patients receiving hematopoietic stem cell transplants for leukemia may do better if their donor has more activating KIR genes (i.e., KIR haplotype-B). In a recent multi-institution clinical trial of patients with metastatic renal cell carcinoma receiving high-dose IL2 (HD-IL2), 25 % of patients showed a complete or partial tumor response to this therapy. We genotyped KIR and KIR-ligand genes for these patients (n = 107) and tested whether KIR/KIR-ligand genotypes correlated with patient clinical outcomes. In these analyses, we did not find any significant association of KIR/KIR-ligand genotype (either KIR-ligand missing or the presence of KIR haplotype-B) with patient outcome in response to the HD-IL2 therapy.
C1 [Wang, Wei; Erbe, Amy K.; Gallenberger, Mikayla; Hess, Dustin; Hank, Jacquelyn A.; Sondel, Paul M.] Univ Wisconsin, Dept Human Oncol, 4159 WIMR Bldg UW Madison Campus, Madison, WI 53705 USA.
[Kim, KyungMann; Carmichael, Lakeesha; Mendonca, Eneida A.; Song, Yiqiang] Univ Wisconsin, Dept Biostat & Med Informat, Madison, WI USA.
[Cheng, Su-Chun] Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA.
[Signoretti, Sabina] Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA.
[Atkins, Michael; Mier, James; McDermott, David F.] Cytokine Working Grp, Rockville, MD USA.
[Atkins, Michael] Georgetown Univ, Dept Med, Washington, DC USA.
[Carlson, Alexander; Mier, James; Panka, David; McDermott, David F.] Beth Israel Deaconess Med Ctr, Div Hematol Oncol, Boston, MA 02215 USA.
[Weiss, Jonathan M.] NCI, Biol Resources Branch, Frederick, MD 21701 USA.
[Mendonca, Eneida A.; Sondel, Paul M.] Univ Wisconsin, Dept Pediat, Madison, WI 53792 USA.
RP Sondel, PM (reprint author), Univ Wisconsin, Dept Human Oncol, 4159 WIMR Bldg UW Madison Campus, Madison, WI 53705 USA.; Sondel, PM (reprint author), Univ Wisconsin, Dept Pediat, Madison, WI 53792 USA.
EM pmsondel@humonc.wisc.edu
FU Hyundai Hope on Wheels Grant; Midwest Athletes Against Childhood; Stand
Up 2 Cancer; The St. Baldrick's Foundation; American Association of
Cancer Research; University of Wisconsin-Madison Carbone Cancer Center;
NCI-Cytokine Working Group; Public Health Service Grants from the
National Cancer Institute [CA014520, CA021115, CA023318, CA066636,
CA180820, CA180794, CA021076, CA180799, CA14958, CA180816, CA166105,
CA197078]; National Institutes of Health; Department of Health and Human
Services
FX The authors thank the medical and nursing staff that participated in the
care of patients in this study, and especially all patients
participating in this study. Thanks also to Bartosz Grzywacz and Patrick
Reville for their helpful discussions and input. This research was
supported by Hyundai Hope on Wheels Grant; Midwest Athletes Against
Childhood; Stand Up 2 Cancer; The St. Baldrick's Foundation; American
Association of Cancer Research; University of Wisconsin-Madison Carbone
Cancer Center; by NCI-Cytokine Working Group and supported in part by
Public Health Service Grants CA014520, CA021115, CA023318, CA066636,
CA180820, CA180794, CA021076, CA180799, CA14958, CA180816, CA166105 and
CA197078, from the National Cancer Institute; the National Institutes of
Health and the Department of Health and Human Services. Its content is
solely the responsibility of the authors and does not necessarily
represent the official views of the National Cancer Institute.
NR 38
TC 0
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U1 4
U2 4
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0340-7004
EI 1432-0851
J9 CANCER IMMUNOL IMMUN
JI Cancer Immunol. Immunother.
PD DEC
PY 2016
VL 65
IS 12
BP 1523
EP 1532
DI 10.1007/s00262-016-1904-8
PG 10
WC Oncology; Immunology
SC Oncology; Immunology
GA EB7UB
UT WOS:000387595000008
PM 27695964
ER
PT J
AU Zhang, F
Zhang, LP
Qi, Y
Xu, H
AF Zhang, Fan
Zhang, Liping
Qi, Yun
Xu, Hong
TI Mitochondrial cAMP signaling
SO CELLULAR AND MOLECULAR LIFE SCIENCES
LA English
DT Review
DE Protein import; Drp1; BH3; Fission; mtDNA; AKAP; TFAM; PKA
ID PROTEIN-KINASE-A; SOLUBLE ADENYLYL-CYCLASE; ELEMENT-BINDING PROTEIN;
CYCLIC-NUCLEOTIDE PHOSPHODIESTERASES; STRESS-MEDIATED MODULATION;
DOMAIN-CONTAINING PROTEINS; COMPLEX-I; ANCHORING PROTEIN; CELL-DEATH;
DEPENDENT PHOSPHORYLATION
AB Cyclic adenosine 3, 5'-monophosphate (cAMP) is a ubiquitous second messenger regulating many biological processes, such as cell migration, differentiation, proliferation and apoptosis. cAMP signaling functions not only on the plasma membrane, but also in the nucleus and in organelles such as mitochondria. Mitochondrial cAMP signaling is an indispensable part of the cytoplasm-mitochondrion crosstalk that maintains mitochondrial homeostasis, regulates mitochondrial dynamics, and modulates cellular stress responses and other signaling pathways. Recently, the compartmentalization of mitochondrial cAMP signaling has attracted great attentions. This new input should be carefully taken into account when we interpret the findings of mitochondrial cAMP signaling. In this review, we summarize previous and recent progress in our understanding of mitochondrial cAMP signaling, including the components of the signaling cascade, and the function and regulation of this signaling pathway in different mitochondrial compartments.
C1 [Zhang, Fan; Qi, Yun; Xu, Hong] NHLBI, NIH, Bldg 10, Bethesda, MD 20892 USA.
[Zhang, Liping] Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD 20892 USA.
RP Xu, H (reprint author), NHLBI, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM xuh5@nhlbi.nih.gov
NR 150
TC 0
Z9 0
U1 10
U2 10
PU SPRINGER BASEL AG
PI BASEL
PA PICASSOPLATZ 4, BASEL, 4052, SWITZERLAND
SN 1420-682X
EI 1420-9071
J9 CELL MOL LIFE SCI
JI Cell. Mol. Life Sci.
PD DEC
PY 2016
VL 73
IS 24
BP 4577
EP 4590
DI 10.1007/s00018-016-2282-2
PG 14
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA EB6KK
UT WOS:000387491800001
ER
PT J
AU Oh, H
Khodr, ZG
Sherman, ME
Palakal, M
Pfeiffer, RM
Linville, L
Geller, BM
Vacek, PM
Weaver, DL
Chicoine, RE
Falk, RT
Horne, HN
Papathomas, D
Patel, DA
Xiang, J
Xu, X
Veenstra, T
Hewitt, SM
Shepherd, JA
Brinton, LA
Figueroa, JD
Gierach, GL
AF Oh, Hannah
Khodr, Zeina G.
Sherman, Mark E.
Palakal, Maya
Pfeiffer, Ruth M.
Linville, Laura
Geller, Berta M.
Vacek, Pamela M.
Weaver, Donald L.
Chicoine, Rachael E.
Falk, Roni T.
Horne, Hisani N.
Papathomas, Daphne
Patel, Deesha A.
Xiang, Jackie
Xu, Xia
Veenstra, Timothy
Hewitt, Stephen M.
Shepherd, John A.
Brinton, Louise A.
Figueroa, Jonine D.
Gierach, Gretchen L.
TI Relation of Serum Estrogen Metabolites with Terminal Duct Lobular Unit
Involution Among Women Undergoing Diagnostic Image-Guided Breast Biopsy
SO HORMONES & CANCER
LA English
DT Article
ID VOLUME MAMMOGRAPHIC DENSITIES; TANDEM MASS-SPECTROMETRY; POSTMENOPAUSAL
WOMEN; CANCER RISK; SEX-HORMONES; RADIOIMMUNOASSAY; RELIABILITY;
VALIDITY; TISSUE; AREA
AB Higher levels of circulating estrogens and estrogen metabolites (EMs) have been associated with higher breast cancer risk. In breast tissues, reduced levels of terminal duct lobular unit (TDLU) involution, as reflected by higher numbers of TDLUs and acini per TDLU, have also been linked to elevated breast cancer risk. However, it is unknown whether reduced TDLU involution mediates the risk associated with circulating EMs. In a cross-sectional analysis of 94 premenopausal and 92 postmenopausal women referred for clinical breast biopsy at an academic facility in Vermont, we examined the associations of 15 EMs, quantified using liquid chromatography-tandem mass spectrometry, with the number of TDLUs and acini count/TDLU using zero-inflated Poisson regression with a robust variance estimator and ordinal logistic regression models, respectively. All analyses were stratified by menopausal status and adjusted for potential confounders. Among premenopausal women, comparing the highest vs. the lowest tertiles, levels of unconjugated estradiol (risk ratio (RR) = 1.74, 95 % confidence interval (CI) = 1.06-2.87, p trend = 0.03), 2-hydroxyestrone (RR = 1.74, 95 % CI = 1.01-3.01, p trend = 0.04), and 4-hydroxyestrone (RR = 1.74, 95 % CI = 0.99-3.06, p trend = 0.04) were associated with significantly higher TDLU count. Among postmenopausal women, higher levels of estradiol (RR = 2.09, 95 % CI = 1.01-4.30, p trend = 0.04) and 16 alpha-hydroxyestrone (RR = 2.27, 95 % CI = 1.29-3.99, p trend = 0.02) were significantly associated with higher TDLU count. Among postmenopausal women, higher levels of EMs, specifically conjugated estrone and 2- and 4-pathway catechols, were also associated with higher acini count/TDLU. Our data suggest that higher levels of serum EMs are generally associated with lower levels of TDLU involution.
C1 [Oh, Hannah; Khodr, Zeina G.; Sherman, Mark E.; Palakal, Maya; Pfeiffer, Ruth M.; Linville, Laura; Falk, Roni T.; Horne, Hisani N.; Papathomas, Daphne; Patel, Deesha A.; Xiang, Jackie; Brinton, Louise A.; Figueroa, Jonine D.; Gierach, Gretchen L.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Oh, Hannah] 9609 Med Ctr Dr,Rm 7E220, Bethesda, MD 20892 USA.
[Sherman, Mark E.] NCI, Canc Prevent Div, Bethesda, MD 20892 USA.
[Geller, Berta M.; Vacek, Pamela M.; Weaver, Donald L.; Chicoine, Rachael E.] Univ Vermont, Burlington, VT USA.
[Xu, Xia; Veenstra, Timothy] Frederick Natl Lab Canc Res, Leidos Biomed Res Inc, Canc Res Technol Program, Frederick, MD USA.
[Hewitt, Stephen M.] NCI, Pathol Lab, Ctr Canc Res, Bldg 10, Bethesda, MD 20892 USA.
[Shepherd, John A.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Figueroa, Jonine D.] Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Edinburgh, Midlothian, Scotland.
RP Oh, H (reprint author), NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.; Oh, H (reprint author), 9609 Med Ctr Dr,Rm 7E220, Bethesda, MD 20892 USA.
EM hannah.oh@nih.gov
RI Gierach, Gretchen/E-1817-2016
OI Gierach, Gretchen/0000-0002-0165-5522
FU Intramural Research Program of the Division of Cancer Epidemiology and
Genetics of the National Cancer Institute; Breast Cancer Research Stamp
Funds; National Cancer Institute [U01CA70013]
FX This study was supported by the Intramural Research Program of the
Division of Cancer Epidemiology and Genetics of the National Cancer
Institute. Breast Cancer Research Stamp Funds (MES, LAB) and cooperative
agreement U01CA70013 (BMG, PMV, DLW, REC) from the National Cancer
Institute funded some of the data collection for this study. The content
of this publication does not necessarily reflect the views or policies
of the Department of Health and Human Services nor does mention of trade
names, commercial products, or organizations imply endorsement by the US
Government.
NR 44
TC 3
Z9 3
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1868-8497
EI 1868-8500
J9 HORM CANCER-US
JI Horm. Cancer
PD DEC
PY 2016
VL 7
IS 5-6
BP 305
EP 315
DI 10.1007/s12672-016-0265-2
PG 11
WC Oncology; Endocrinology & Metabolism
SC Oncology; Endocrinology & Metabolism
GA EB2WZ
UT WOS:000387224600003
PM 27138982
ER
PT J
AU Zhen, DB
Griffith, KA
Ruch, JM
Camphausen, K
Savage, JE
Kim, EJ
Sahai, V
Simeone, DM
Zalupski, MM
AF Zhen, David B.
Griffith, Kent A.
Ruch, Joshua M.
Camphausen, Kevin
Savage, Jason E.
Kim, Edward J.
Sahai, Vaibhav
Simeone, Diane M.
Zalupski, Mark M.
TI A phase I trial of cabozantinib and gemcitabine in advanced pancreatic
cancer
SO INVESTIGATIONAL NEW DRUGS
LA English
DT Article
DE Cabozantinib; XL-184; Gemcitabine; Pancreatic cancer
ID C-MET; CLINICAL-TRIALS; GROWTH-FACTOR; CELLS; METASTASIS; SURVIVAL;
MOTILITY; RECEPTOR
AB Background Cabozantinib and gemcitabine improve tumor control in pancreatic ductal adenocarcinoma (PDAC) in preclinical models through c-Met inhibition. We sought to determine the maximum tolerated dose (MTD) of this combination in patients with advanced PDAC. Methods Patients with aecurrency sign1 prior treatment and adequate performance status were eligible. Cabozantinib was given orally once daily, beginning day (-)7 and continued with gemcitabine given intravenously on days 1, 8, and 15 every 28 days. Dose level was assigned using Time to Event Continual Reassessment Method (TITE-CRM). Primary endpoint was MTD, defined as the highest dose level at which aecurrency sign25 % of patients incurred a dose-limiting toxicity (DLT). Secondary endpoints included response rate, progression-free survival (PFS), overall survival (OS) and urinary biomarker assessment. Results Twelve patients were enrolled and treated with 10 patients evaluable for DLT. The probability of DLT was > 25 % for all dose levels tested, and thus an MTD was not determined. DLTs included grade 3 ALT/AST elevations and thrombocytopenia. Three patients had partial responses, but each discontinued therapy due to toxicity. Median PFS and OS were 4.7 (95 % CI: 1.4-9.7) and 10.1 months (95 % CI: 3.6-20.6). Exploratory biomarker analysis showed correlation of c-Met and VEGF levels with response. Conclusions An MTD for the combination was not established. Cabozantinib and gemcitabine appear impractical for further development due to DLT at low doses and continuing toxicities with ongoing therapy. Acknowledging the small sample size, responses were seen suggesting further investigation of c-Met inhibition in PDAC may be warranted.
C1 [Zhen, David B.; Ruch, Joshua M.; Kim, Edward J.; Sahai, Vaibhav; Zalupski, Mark M.] Univ Michigan, Dept Internal Med, Div Hematol Oncol, 3-219 CC,1500 E Med Ctr Dr,SPC 5934, Ann Arbor, MI 48109 USA.
[Griffith, Kent A.] Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA.
[Camphausen, Kevin; Savage, Jason E.] NCI, Radiat Oncol Branch, NIH, Bldg 10, Bethesda, MD 20892 USA.
[Simeone, Diane M.] Univ Michigan, Dept Surg, Ann Arbor, MI 48109 USA.
RP Zalupski, MM (reprint author), Univ Michigan, Dept Internal Med, Div Hematol Oncol, 3-219 CC,1500 E Med Ctr Dr,SPC 5934, Ann Arbor, MI 48109 USA.
EM zalupski@med.umich.edu
FU NCI of the National Institutes of Health [P30CA046592]; Michigan
Institute for Clinical and Health Research (MICHR) [UL1TR000433];
intramural program of the NCI
FX The authors thank Bill Reisdorph for his excellent management of the
study specific IND 114,716. Young Lee processed urinary samples for the
correlative molecular biomarker analysis. Donald Bottaro of the Urologic
Oncology Branch at the National Cancer Institute (NCI) provided access
to the electrochemiluminescence instrument for the c-Met assay.
Exelixis, Inc. provided cabozantinib for this study. Research reported
in this publication was supported by the NCI of the National Institutes
of Health under award number P30CA046592, Michigan Institute for
Clinical and Health Research (MICHR) under award number UL1TR000433, and
funded in part by the intramural program of the NCI.
NR 29
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U1 4
U2 4
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0167-6997
EI 1573-0646
J9 INVEST NEW DRUG
JI Invest. New Drugs
PD DEC
PY 2016
VL 34
IS 6
BP 733
EP 739
DI 10.1007/s10637-016-0376-1
PG 7
WC Oncology; Pharmacology & Pharmacy
SC Oncology; Pharmacology & Pharmacy
GA EB7QJ
UT WOS:000387584100007
PM 27439894
ER
PT J
AU Blanch-Hartigan, D
Chawla, N
Moser, RP
Rutten, LJF
Hesse, BW
Arora, NK
AF Blanch-Hartigan, Danielle
Chawla, Neetu
Moser, Richard P.
Rutten, Lila J. Finney
Hesse, Bradford W.
Arora, Neeraj K.
TI Trends in cancer survivors' experience of patient-centered
communication: results from the Health Information National Trends
Survey (HINTS)
SO JOURNAL OF CANCER SURVIVORSHIP
LA English
DT Article
DE Patient-centered care; Patient-provider communication; Cancer
survivorship; Emotions; Uncertainty
ID QUALITY-OF-CARE; PERCEPTIONS; ONCOLOGISTS; PHYSICIANS
AB Two Institute of Medicine reports almost a decade apart suggest that cancer survivors often feel "lost in transition" and experience suboptimal quality of care. The six core functions of patient-centered communication: managing uncertainty, responding to emotions, making decisions, fostering healing relationships, enabling self-management, and exchanging information, represent a central aspect of survivors' care experience that has not been systematically investigated.
Nationally representative data from four administrations of the Health Information National Trends Survey (HINTS) was merged with combined replicate weights using the jackknife replication method. Linear and logistic regression models were used to assess (1) characteristics of cancer survivors (N = 1794) who report suboptimal patient-centered communication and (2) whether survivors' patient-centered communication experience changed from 2007 to 2013.
One third to one half of survivors report suboptimal patient-centered communication, particularly on core functions of providers helping manage uncertainty (48 %) and responding to emotions (49 %). In a fully adjusted linear regression model, survivors with more education (Wald F = 2.84, p = .04), without a usual source of care (Wald F = 11.59, p < .001), and in poorer health (Wald F = 9.08, p < .001) were more likely to report less patient-centered communication. Although ratings of patient-centered communication improved over time (p trend = .04), this trend did not remain significant in fully adjusted models.
Despite increased attention to survivorship, many survivors continue to report suboptimal communication with their health care providers.
Survivorship communication should include managing uncertainty about future risk and address survivors' emotional needs. Efforts to improve patient-centered communication should focus on survivors without a usual source of care and in poorer health.
C1 [Blanch-Hartigan, Danielle] Bentley Univ, Dept Nat & Appl Sci, Jennison 103,175 Forest St, Waltham, MA 02452 USA.
[Chawla, Neetu] Kaiser Permanente Northern Calif, Div Res, Oakland, CA USA.
[Moser, Richard P.; Hesse, Bradford W.] NCI, Div Canc Control & Populat Sci, NIH, Bethesda, MD 20892 USA.
[Rutten, Lila J. Finney] Mayo Clin, Robert D & Patricia E Kern Ctr Sci Hlth Care Deli, Rochester, MN USA.
[Arora, Neeraj K.] Patient Ctr Outcomes Res Inst, Improving Hlth Syst, Washington, DC USA.
RP Blanch-Hartigan, D (reprint author), Bentley Univ, Dept Nat & Appl Sci, Jennison 103,175 Forest St, Waltham, MA 02452 USA.
EM danielleblanch@gmail.com
FU National Cancer Institute [HHSN26120100064C]
FX The Health Information National Trends Survey is supported by contract
number HHSN26120100064C from the National Cancer Institute. The views
expressed in the manuscript do not necessarily represent the views of
the US Federal Government.
NR 30
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U1 5
U2 5
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1932-2259
EI 1932-2267
J9 J CANCER SURVIV
JI J. Cancer Surviv.-Res. Pract.
PD DEC
PY 2016
VL 10
IS 6
BP 1067
EP 1077
DI 10.1007/s11764-016-0550-7
PG 11
WC Oncology; Social Sciences, Biomedical
SC Oncology; Biomedical Social Sciences
GA EB4JO
UT WOS:000387337700011
PM 27193357
ER
PT J
AU Kenzik, KM
Kent, EE
Martin, MY
Bhatia, S
Pisu, M
AF Kenzik, Kelly M.
Kent, Erin E.
Martin, Michelle Y.
Bhatia, Smita
Pisu, Maria
TI Chronic condition clusters and functional impairment in older cancer
survivors: a population-based study
SO JOURNAL OF CANCER SURVIVORSHIP
LA English
DT Article
DE Cancer survivor; Comorbidity; Function; Geriatric
ID QUALITY-OF-LIFE; CHILDHOOD-CANCER; HEALTH-OUTCOMES; MEDICARE;
COMPLICATIONS; PREVALENCE; DISORDER; DISEASE
AB The purpose of the study is to identify chronic condition clusters at pre- and post-cancer diagnosis, evaluate predictors of developing clusters post-cancer, and examine the impact on functional impairment among older cancer survivors.
We identified 5991 survivors age 65 and older of prostate, breast, colorectal, lung, bladder, kidney, head and neck, and gynecologic cancer and non-Hodgkin lymphoma from the Surveillance, Epidemiology and End Results-Medicare Health Outcomes Survey resource. Survivors completed surveys pre- and post-cancer diagnosis on 13 chronic conditions and functional status. Among those with aeyen2 conditions, exploratory factor analysis identified clusters of conditions. Differences in cluster frequency from pre- to post-cancer diagnosis were evaluated across the top five cancer types using chi-square tests. Modified Poisson regression models estimated the relative risk of developing clusters post-diagnosis. Chi-square tests evaluated associations between function and clusters.
Clusters included the following: cardiovascular disease cluster (pre 6.1 % and post 7.7 %), musculoskeletal cluster (28.2 % and 29.3 %), metabolic cluster (14.9 % and 17.6 %), and the major depressive disorder risk (MDDr) + gastrointestinal (GI) + pulmonary condition cluster (5.8 % and 8.7 %). Increases in MDDr + GI + Pulmonary cluster from pre- to post-cancer diagnosis were observed for prostate, lung, and colorectal cancer survivors. Functional impairment was more prevalent in survivors with defined clusters, especially in MDDr + GI + pulmonary, compared to survivors with aeyen2 un-clustered conditions.
Distinct condition clusters of two or more chronic conditions are prevalent among older cancer survivors. Cluster prevalence increases from pre- to post-cancer diagnosis and these clusters have a significant impact on functional limitations.
Tailored management on specific multimorbidity patterns will have implications for functional outcomes among older survivors.
C1 [Kenzik, Kelly M.; Bhatia, Smita] Univ Alabama Birmingham, Inst Canc Outcomes & Survivorship, Birmingham, AL 35233 USA.
[Kent, Erin E.] NCI, Outcomes Res Branch, Div Canc Control & Populat Sci, Rockville, MD USA.
[Martin, Michelle Y.] Univ Tennessee, Ctr Hlth Sci, Memphis, TN 38163 USA.
[Pisu, Maria] Univ Alabama Birmingham, Div Prevent Med, Birmingham, AL 35233 USA.
RP Kenzik, KM (reprint author), Univ Alabama Birmingham, Inst Canc Outcomes & Survivorship, Birmingham, AL 35233 USA.
EM kkenzik@uab.edu
FU Agency for Healthcare Research and Quality [T32HS013852, K12HS023009]
FX KMK was supported by grants T32HS013852 and K12HS023009 from the Agency
for Healthcare Research and Quality. The content is solely the
responsibility of the authors and does not necessarily represent the
official views of the National Cancer Institute or AHRQ.
NR 33
TC 1
Z9 1
U1 7
U2 7
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1932-2259
EI 1932-2267
J9 J CANCER SURVIV
JI J. Cancer Surviv.-Res. Pract.
PD DEC
PY 2016
VL 10
IS 6
BP 1096
EP 1103
DI 10.1007/s11764-016-0553-4
PG 8
WC Oncology; Social Sciences, Biomedical
SC Oncology; Biomedical Social Sciences
GA EB4JO
UT WOS:000387337700014
PM 27229869
ER
PT J
AU Gozalo, AS
Elkins, WR
Lambert, LE
Stock, F
Thomas, ML
Woodward, RA
AF Gozalo, Alfonso S.
Elkins, William R.
Lambert, Lynn E.
Stock, Frida
Thomas, Marvin L., III
Woodward, Ruth A.
TI Genetic diversity of Klebsiella pneumoniae isolates during an outbreak
in a non-human primate research colony
SO JOURNAL OF MEDICAL PRIMATOLOGY
LA English
DT Article
DE Aotus nancymai; automated repetitive extragenic palindromic-polymerase
chain reaction; Cebidae; DNA fingerprinting; Klebsiellosis; owl monkey;
rep-PCR
ID HYPERMUCOVISCOSITY PHENOTYPE; ANTIBIOTIC-RESISTANCE; ENVIRONMENTS;
INFECTIONS; PATHOGENS; MONKEYS
AB BackgroundKlebsiella pneumoniae can be a serious pathogen in non-human primates, particularly Neotropical monkeys.
MethodsDuring a K.pneumoniae outbreak in an owl monkey research colony, 13 K.pneumoniae isolates were DNA fingerprinted by automated repetitive extragenic palindromic-polymerase chain reaction and the profiles compared to isolates obtained from other non-human primate species during the same time period and isolates from previous outbreaks.
ResultsEleven different types of K.pneumoniae were circulating in the owl monkey colony at the time of the outbreak. When comparing owl monkey isolates relatedness to previous colony outbreak isolates and squirrel monkey and capuchin monkey isolates, all were different.
ConclusionsThese results agree with recent reports where K.pneumoniae nosocomial isolates in hospital settings can have high genetic diversity, and multiple strains can be circulating simultaneously. This potential genetic diversity should be considered when designing strategies for controlling K.pneumoniae outbreaks in captive non-human primate colonies.
C1 [Gozalo, Alfonso S.; Elkins, William R.] NIAID, Comparat Med Branch, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Lambert, Lynn E.] NIAID, Lab Malaria Immunol & Vaccinol, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Lambert, Lynn E.] SoBran Inc, Bethesda, MD USA.
[Stock, Frida] NIH, Dept Lab Med, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA.
[Thomas, Marvin L., III] NIH, Div Vet Resources, Bldg 10, Bethesda, MD 20892 USA.
[Woodward, Ruth A.] NICHHD, Res Anim Med Branch, NIH, Bethesda, MD 20892 USA.
RP Gozalo, AS (reprint author), NIAID, Comparat Med Branch, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM gozaloa@niaid.nih.gov
FU Intramural Research Program of the National Institutes of Health,
National Institute of Allergy and Infectious Diseases, Comparative
Medicine Branch; Laboratory of Malaria Immunology and Vaccinology;
Department of Laboratory Medicine, Clinical Center, National Institutes
of Health, and the Office of Research Services
FX This study was supported by the Intramural Research Program of the
National Institutes of Health, National Institute of Allergy and
Infectious Diseases, Comparative Medicine Branch; Laboratory of Malaria
Immunology and Vaccinology; Department of Laboratory Medicine, Clinical
Center, National Institutes of Health, and the Office of Research
Services. Abstract presented at the 64th AALAS National Meeting,
Baltimore, MD, October 27-31, 2013.
NR 27
TC 0
Z9 0
U1 1
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0047-2565
EI 1600-0684
J9 J MED PRIMATOL
JI J. Med. Primatol.
PD DEC
PY 2016
VL 45
IS 6
BP 312
EP 317
DI 10.1111/jmp.12229
PG 6
WC Veterinary Sciences; Zoology
SC Veterinary Sciences; Zoology
GA EB4SM
UT WOS:000387363700005
ER
PT J
AU Rosenkrantz, AB
Verma, S
Choyke, P
Eberhardt, SC
Eggener, SE
Gaitonde, K
Haider, MA
Margolis, DJ
Marks, LS
Pinto, P
Sonn, GA
Taneja, SS
AF Rosenkrantz, Andrew B.
Verma, Sadhna
Choyke, Peter
Eberhardt, Steven C.
Eggener, Scott E.
Gaitonde, Krishnanath
Haider, Masoom A.
Margolis, Daniel J.
Marks, Leonard S.
Pinto, Peter
Sonn, Geoffrey A.
Taneja, Samir S.
TI Prostate Magnetic Resonance Imaging and Magnetic Resonance Imaging
Targeted Biopsy in Patients with a Prior Negative Biopsy: A Consensus
Statement by AUA and SAR
SO JOURNAL OF UROLOGY
LA English
DT Article
DE prostatic neoplasms; biopsy; magnetic resonance imaging; consensus
ID ULTRASOUND FUSION BIOPSY; CANCER; MRI; SYSTEM; LOCALIZATION; GUIDANCE;
ANTIGEN; LESION; MEN
AB Purpose: After an initial negative biopsy there is an ongoing need for strategies to improve patient selection for repeat biopsy as well as the diagnostic yield from repeat biopsies.
Materials and Methods: As a collaborative initiative of the AUA (American Urological Association) and SAR (Society of Abdominal Radiology) Prostate Cancer Disease Focused Panel, an expert panel of urologists and radiologists conducted a literature review and formed consensus statements regarding the role of prostate magnetic resonance imaging and magnetic resonance imaging targeted biopsy in patients with a negative biopsy, which are summarized in this review.
Results: The panel recognizes that many options exist for men with a previously negative biopsy. If a biopsy is recommended, prostate magnetic resonance imaging and subsequent magnetic resonance imaging targeted cores appear to facilitate the detection of clinically significant disease over standardized repeat biopsy. Thus, when high quality prostate magnetic resonance imaging is available, it should be strongly considered for any patient with a prior negative biopsy who has persistent clinical suspicion for prostate cancer and who is under evaluation for a possible repeat biopsy. The decision of whether to perform magnetic resonance imaging in this setting must also take into account the results of any other biomarkers and the cost of the examination, as well as the availability of high quality prostate magnetic resonance imaging interpretation. If magnetic resonance imaging is done, it should be performed, interpreted and reported in accordance with PI-RADS version 2 (v2) guidelines. Experience of the reporting radiologist and biopsy operator are required to achieve optimal results and practices integrating prostate magnetic resonance imaging into patient care are advised to implement quality assurance programs to monitor targeted biopsy results.
Conclusions: Patients receiving a PI-RADS assessment category of 3 to 5 warrant repeat biopsy with image guided targeting. While transrectal ultrasound guided magnetic resonance imaging fusion or in-bore magnetic resonance imaging targeting may be valuable for more reliable targeting, especially for lesions that are small or in difficult locations, in the absence of such targeting technologies cognitive (visual) targeting remains a reasonable approach in skilled hands. At least 2 targeted cores should be obtained from each magnetic resonance imaging defined target. Given the number of studies showing a proportion of missed clinically significant cancers by magnetic resonance imaging targeted cores, a case specific decision must be made whether to also perform concurrent systematic sampling. However, performing solely targeted biopsy should only be considered once quality assurance efforts have validated the performance of prostate magnetic resonance imaging interpretations with results consistent with the published literature. In patients with negative or low suspicion magnetic resonance imaging (PI-RADS assessment category of 1 or 2, respectively), other ancillary markers (ie PSA, PSAD, PSAV, PCA3, PHI, 4K) may be of value in identifying patients warranting repeat systematic biopsy, although further data are needed on this topic. If a repeat biopsy is deferred on the basis of magnetic resonance imaging findings, then continued clinical and laboratory followup is advised and consideration should be given to incorporating repeat magnetic resonance imaging in this diagnostic surveillance regimen.
C1 [Rosenkrantz, Andrew B.] NYU, Dept Radiol, Langone Med Ctr, 560 1St Ave, New York, NY 10016 USA.
[Taneja, Samir S.] NYU, Langone Med Ctr, Dept Urol Oncol, New York, NY USA.
[Margolis, Daniel J.] Weill Cornell Med Coll, Dept Radiol, New York, NY USA.
[Verma, Sadhna] Univ Cincinnati, Coll Med, Dept Radiol, Cincinnati, OH USA.
[Gaitonde, Krishnanath] Univ Cincinnati, Coll Med, Dept Urol, Cincinnati, OH USA.
[Choyke, Peter] NCI, Mol Imaging Program, Bethesda, MD 20892 USA.
[Pinto, Peter] NCI, Urol Oncol Branch, Bethesda, MD 20892 USA.
[Pinto, Peter] NIH, Ctr Clin, Bethesda, MD 20892 USA.
[Eberhardt, Steven C.] Univ New Mexico, Dept Radiol, Albuquerque, NM 87131 USA.
[Eggener, Scott E.] Univ Chicago Med, Urol Sect, Chicago, IL USA.
[Haider, Masoom A.] Univ Toronto, Sunnybrook Hlth Sci Ctr, Dept Med Imaging, Toronto, ON, Canada.
[Marks, Leonard S.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Radiol, Los Angeles, CA 90095 USA.
[Marks, Leonard S.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Urol, Los Angeles, CA 90095 USA.
[Sonn, Geoffrey A.] Stanford Univ, Dept Urol, Sch Med, Stanford, CA 94305 USA.
RP Rosenkrantz, AB (reprint author), NYU, Sch Med, Langone Med Ctr, Dept Radiol,Ctr Biomed Imaging, 660 First Ave,3rd Floor, New York, NY 10016 USA.
EM Andrew.Rosenkrantz@nyumc.org
NR 29
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Z9 1
U1 4
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0022-5347
EI 1527-3792
J9 J UROLOGY
JI J. Urol.
PD DEC
PY 2016
VL 196
IS 6
BP 1613
EP 1618
DI 10.1016/j.juro.2016.06.079
PG 6
WC Urology & Nephrology
SC Urology & Nephrology
GA EB5QS
UT WOS:000387436000006
PM 27320841
ER
PT J
AU Abdel-Wahab, N
Lopez-Olivo, MA
Pinto-Patarroyo, GP
Suarez-Almazor, ME
AF Abdel-Wahab, N.
Lopez-Olivo, M. A.
Pinto-Patarroyo, G. P.
Suarez-Almazor, M. E.
TI Systematic review of case reports of antiphospholipid syndrome following
infection
SO LUPUS
LA English
DT Review
DE anticardiolipin antibodies; antiphospholipid antibodies; lupus
anticoagulant; infection; systematic review
ID INTERNATIONAL CONSENSUS STATEMENT; ANTICARDIOLIPIN ANTIBODIES;
LUPUS-ERYTHEMATOSUS; CLASSIFICATION CRITERIA; BETA(2)-GLYCOPROTEIN I;
AUTOIMMUNE-DISEASE; APOLIPOPROTEIN-H; POLYMORPHISM; AUTOANTIBODIES;
PREVALENCE
AB Objective The objective of this study was to conduct a systematic review of case reports documenting the development of antiphospholipid syndrome or antiphospholipid syndrome-related features after an infection.
Methods We searched Medline, EMBASE, Web of Science, PubMed ePubs, and The Cochrane Library - CENTRAL through March 2015 without restrictions. Studies reporting cases of antiphospholipid syndrome or antiphospholipid syndrome-related features following an infection were included.
Results Two hundred and fifty-nine publications met inclusion criteria, reporting on 293 cases. Three different groups of patients were identified; group 1 included patients who fulfilled the criteria for definitive antiphospholipid syndrome (24.6%), group 2 included patients who developed transient antiphospholipid antibodies with thromboembolic phenomena (43.7%), and group 3 included patients who developed transient antiphospholipid antibodies without thromboembolic events (31.7%). The most common preceding infection was viral (55.6%). In cases that developed thromboembolic events Human immunodeficiency and Hepatitis C viruses were the most frequently reported. Parvovirus B19 was the most common in cases that developed antibodies without thromboembolic events. Hematological manifestations and peripheral thrombosis were the most common clinical manifestations. Positive anticardiolipin antibodies were the most frequent antibodies reported, primarily coexisting IgG and IgM isotypes. Few patients in groups 1 and 2 had persistent antiphospholipid antibodies for more than 6 months. Outcome was variable with some cases reporting persistent antiphospholipid syndrome features and others achieving complete resolution of clinical events.
Conclusions Development of antiphospholipid antibodies with all traditional manifestations of antiphospholipid syndrome were observed after variety of infections, most frequently after chronic viral infections with Human immunodeficiency and Hepatitis C. The causal relationship between infection and antiphospholipid syndrome cannot be established, but the possible contribution of various infections in the pathogenesis of antiphospholipid syndrome need further longitudinal and controlled studies to establish the incidence, and better quantify the risk and the outcomes of antiphospholipid-related events after infection.
C1 [Abdel-Wahab, N.; Lopez-Olivo, M. A.; Suarez-Almazor, M. E.] Univ Texas MD Anderson Canc Ctr, Dept Gen Internal Med, Sect Rheumatol & Clin Immunol, Houston, TX 77030 USA.
[Abdel-Wahab, N.] Assiut Univ Hosp, Rheumatol & Rehabil Dept, Assiut, Egypt.
[Pinto-Patarroyo, G. P.] NHGRI, NIH, Bethesda, MD 20892 USA.
RP Suarez-Almazor, ME (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Gen Internal Med, Unit 1465,1515 Holcombe Blvd, Houston, TX 77030 USA.
EM msalmazor@mdanderson.org
FU National Institute for Arthritis, Musculoskeletal and Skin Disorders
(NIAMS) [AR053593]
FX The author(s) disclosed receipt of the following financial support for
the research, authorship, and/or publication of this article: Dr
Suarez-Almazor has a K24 career award from the National Institute for
Arthritis, Musculoskeletal and Skin Disorders (NIAMS: grant number
AR053593). The funding agency had no role in the study's design,
conduct, and reporting.
NR 42
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Z9 0
U1 3
U2 3
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 0961-2033
EI 1477-0962
J9 LUPUS
JI Lupus
PD DEC
PY 2016
VL 25
IS 14
BP 1520
EP 1531
DI 10.1177/0961203316640912
PG 12
WC Rheumatology
SC Rheumatology
GA EB5VC
UT WOS:000387447700002
PM 27060064
ER
PT J
AU Quiroz, C
Gulyani, S
Ruiqian, W
Bonaventura, J
Cutler, R
Pearson, V
Allen, RR
Earley, CJ
Mattson, MP
Ferre, S
AF Quiroz, Cesar
Gulyani, Seema
Ruiqian, Wan
Bonaventura, Jordi
Cutler, Roy
Pearson, Virginia
Allen, Richard R.
Earley, Christopher J.
Mattson, Mark P.
Ferre, Sergi
TI Adenosine receptors as markers of brain iron deficiency: Implications
for Restless Legs Syndrome
SO NEUROPHARMACOLOGY
LA English
DT Article
DE Restless Legs Syndrome; Brain iron deficiency; Adenosine A(1) receptor;
Adenosine A(2A) receptor; Dopamine D-2 receptor
ID WILLIS-EKBOM DISEASE; RAT-BRAIN; A(2A) RECEPTORS; DOPAMINE D-1;
HOMEOSTATIC SLEEP; A(1) RECEPTORS; EXPRESSION; CAFFEINE; DEPRIVATION;
NEUROTRANSMISSION
AB Deficits of sensorimotor integration with periodic limb movements during sleep (PLMS) and hyper arousal and sleep disturbances in Restless Legs Syndrome (RLS) constitute two pathophysiologically distinct but interrelated clinical phenomena, which seem to depend mostly on alterations in dopaminergic and glutamatergic neurotransmission, respectively. Brain iron deficiency is considered as a main pathogenetic mechanism in RLS. Rodents with brain iron deficiency represent a valuable pathophysiological model of RLS, although they do not display motor disturbances. Nevertheless, they develop the main neurochemical dopaminergic changes found in RLS, such as decrease in striatal dopamine D-2 receptor density. On the other hand, brain iron deficient mice exhibit the characteristic pattern of hyperarousal in RLS, providing a tool to find the link between brain iron deficiency and sleep disturbances in RLS. The present study provides evidence for a role of the endogenous sleep-promoting factor adenosine. Three different experimental preparations, long-term (22 weeks) severe or moderate iron deficient (ID) diets (3- or 7-ppm iron diet) in mice and short-term (3 weeks) severe ID diet (3-ppm iron diet) in rats, demonstrated a significant downregulation (Western blotting in mouse and radio-ligand binding saturation experiments in rat brain tissue) of adenosine A(1) receptors (MR) in the cortex and striatum, concomitant to striatal D2R downregulation. On the other hand, the previously reported upregulation of adenosine A(2A) receptors (A2AR) was only observed with severe ID in both mice and rats. The results suggest a key role for MR downregulation in the PLMS and hyperarousal in RLS. Published by Elsevier Ltd.
C1 [Quiroz, Cesar; Bonaventura, Jordi; Ferre, Sergi] NIDA, Integrat Neurobiol Sect, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
[Gulyani, Seema; Ruiqian, Wan; Cutler, Roy; Mattson, Mark P.] NIA, Lab Neurosci, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
[Pearson, Virginia; Allen, Richard R.; Earley, Christopher J.] Johns Hopkins Sch Med, Dept Neurol, Ctr Restless Legs Study, Baltimore, MD 21224 USA.
RP Ferre, S (reprint author), NIDA, Integrat Neurobiol Sect, IRP, Triad Technol Bldg,333 Cassell Dr, Baltimore, MD 21224 USA.
EM sferre@intra.nida.nih.gov
RI Ferre, Sergi/K-6115-2014
OI Ferre, Sergi/0000-0002-1747-1779
FU National Institute on Drug Abuse; National Institute on Aging
FX Work supported by the intramural funds of the National Institute on Drug
Abuse and the National Institute on Aging.
NR 43
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U1 5
U2 5
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0028-3908
EI 1873-7064
J9 NEUROPHARMACOLOGY
JI Neuropharmacology
PD DEC
PY 2016
VL 111
BP 160
EP 168
DI 10.1016/j.neuropharm.2016.09.002
PG 9
WC Neurosciences; Pharmacology & Pharmacy
SC Neurosciences & Neurology; Pharmacology & Pharmacy
GA EB2MS
UT WOS:000387197100013
PM 27600688
ER
PT J
AU Schoenbaum, G
Chang, CY
Lucantonio, F
Takahashi, YK
AF Schoenbaum, Geoffrey
Chang, Chun-Yun
Lucantonio, Federica
Takahashi, Yuji K.
TI Thinking Outside the Box: Orbitofrontal Cortex, Imagination, and How We
Can Treat Addiction
SO NEUROPSYCHOPHARMACOLOGY
LA English
DT Review
ID DORSOLATERAL PREFRONTAL CORTEX; REWARD PREDICTION ERRORS; CHRONIC
COCAINE; REINFORCER DEVALUATION; AMPHETAMINE EXPOSURE; BASOLATERAL
AMYGDALA; DECISION-MAKING; FRONTAL-CORTEX; BEHAVIOR; LESIONS
AB Addiction involves an inability to control drug-seeking behavior. While this may be thought of as secondary to an overwhelming desire for drugs, it could equally well reflect a failure of the brain mechanisms that allow addicts to learn about and mentally simulate non-drug consequences. Importantly, this process of mental simulation draws upon, but is not normally bound by, our past experiences. Rather we have the ability to think outside the box of our past, integrating knowledge gained from a variety of similar and not-so-similar life experiences to derive estimates or imagine what might happen next. These estimates influence our current behavior directly and also affect future behavior by serving as the background against which outcomes are evaluated to support learning. Here we will review evidence, from our own work using a Pavlovian over-expectation task as well as from other sources, that the orbitofrontal cortex is a critical node in the neural circuit that generates these estimates. Further we will offer the specific hypothesis that degradation of this function secondary to drug-induced changes is a critical and likely addressable part of addiction.
C1 [Schoenbaum, Geoffrey; Chang, Chun-Yun; Lucantonio, Federica; Takahashi, Yuji K.] NIDA, Intramural Res Program, 251 Bayview Dr, Baltimore, MD 21224 USA.
RP Schoenbaum, G (reprint author), NIDA, Intramural Res Program, 251 Bayview Dr, Baltimore, MD 21224 USA.
EM geoffrey.schoenbaum@nih.gov
OI Schoenbaum, Geoffrey/0000-0001-8180-0701
FU Intramural Research Program at the National Institute on Drug Abuse
FX This work was supported by the Intramural Research Program at the
National Institute on Drug Abuse. The authors declare no conflict of
interest.
NR 74
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U1 14
U2 14
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0893-133X
EI 1740-634X
J9 NEUROPSYCHOPHARMACOL
JI Neuropsychopharmacology
PD DEC
PY 2016
VL 41
IS 13
BP 2966
EP 2976
DI 10.1038/npp.2016.147
PG 11
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA EB7MC
UT WOS:000387570700003
PM 27510424
ER
PT J
AU Barkus, C
Korn, C
Stumpenhorst, K
Laatikainen, LM
Ballard, D
Lee, S
Sharp, T
Harrison, PJ
Bannerman, DM
Weinberger, DR
Chen, JS
Tunbridge, EM
AF Barkus, Chris
Korn, Clio
Stumpenhorst, Katharina
Laatikainen, Linda M.
Ballard, Dominic
Lee, Sheena
Sharp, Trevor
Harrison, Paul J.
Bannerman, David M.
Weinberger, Daniel R.
Chen, Jingshan
Tunbridge, Elizabeth M.
TI Genotype-Dependent Effects of COMT Inhibition on Cognitive Function in a
Highly Specific, Novel Mouse Model of Altered COMT Activity
SO NEUROPSYCHOPHARMACOLOGY
LA English
DT Article
ID CATECHOL-O-METHYLTRANSFERASE; REACTION-TIME-TASK; RAT PREFRONTAL CORTEX;
VAL(158)MET POLYMORPHISM; PSYCHIATRIC-DISORDERS; EXECUTIVE FUNCTION;
GENETIC-VARIATION; DOPAMINE RELEASE; PANIC DISORDER; DEFICIENT MICE
AB Catechol-O-methyltransferase (COMT) modulates dopamine levels in the prefrontal cortex. The human gene contains a polymorphism (Val(158)Met) that alters enzyme activity and influences PFC function. It has also been linked with cognition and anxiety, but the findings are mixed. We therefore developed a novel mouse model of altered COMT activity. The human Met allele was introduced into the native mouse COMT gene to produce COMT-Met mice, which were compared with their wild-type littermates. The model proved highly specific: COMT-Met mice had reductions in COMT abundance and activity, compared with wild-type mice, explicitly in the absence of off-target changes in the expression of other genes. Despite robust alterations in dopamine metabolism, we found only subtle changes on certain cognitive tasks under baseline conditions (eg, increased spatial novelty preference in COMT-Met mice vs wild-type mice). However, genotype differences emerged after administration of the COMT inhibitor tolcapone: performance of wild-type mice, but not COMT-Met mice, was improved on the 5-choice serial reaction time task after tolcapone administration. There were no changes in anxiety-related behaviors in the tests that we used. Our findings are convergent with human studies of the Val(158)Met polymorphism, and suggest that COMT's effects are most prominent when the dopamine system is challenged. Finally, they demonstrate the importance of considering COMT genotype when examining the therapeutic potential of COMT inhibitors.
C1 [Barkus, Chris; Korn, Clio; Stumpenhorst, Katharina; Laatikainen, Linda M.; Harrison, Paul J.; Tunbridge, Elizabeth M.] Univ Oxford, Dept Psychiat, Oxford, England.
[Ballard, Dominic] Univ Oxford, Sch Med, Oxford, England.
[Lee, Sheena] Univ Oxford, Dept Physiol Anat & Genet, Oxford, England.
[Sharp, Trevor] Univ Oxford, Dept Pharmacol, Oxford, England.
[Harrison, Paul J.; Tunbridge, Elizabeth M.] Oxford Hlth NHS Fdn Trust, Oxford, England.
[Bannerman, David M.] Univ Oxford, Dept Expt Psychol, Oxford, England.
[Weinberger, Daniel R.] Johns Hopkins Univ, Lieber Inst Brain Dev, Baltimore, MD USA.
[Chen, Jingshan] NIMH, NIH, Bethesda, MD 20892 USA.
RP Tunbridge, EM (reprint author), Univ Oxford, Warneford Hosp, Dept Psychiat, Neurosci Bldg, Oxford OX3 7JX, Oxon, England.
EM elizabeth.tunbridge@psych.ox.ac.uk
FU Intramural Research Program of the NIMH, Bethesda MD, USA; UK Medical
Research Council grant [G0700983]; Wellcome Trust; Royal Society
[RG100516]; Wellcome Trust Senior Fellowship [087736]; University
Research Fellowship - Royal Society
FX The authors declare no conflict of interest. This research was funded by
the Intramural Research Program of the NIMH, Bethesda MD, USA to the
Weinberger Laboratory, and by a UK Medical Research Council grant
(G0700983) to PJH and EMT. Additional funding from Wellcome Trust
studentships awarded to CK and KS, and a grant to EMT from the Royal
Society (RG100516) and a Wellcome Trust Senior Fellowship (087736)
awarded to DB. EMT is funded by a University Research Fellowship awarded
by the Royal Society.
NR 55
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PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0893-133X
EI 1740-634X
J9 NEUROPSYCHOPHARMACOL
JI Neuropsychopharmacology
PD DEC
PY 2016
VL 41
IS 13
BP 3060
EP 3069
DI 10.1038/npp.2016.119
PG 10
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA EB7MC
UT WOS:000387570700013
PM 27388330
ER
PT J
AU Kopin, I
AF Kopin, Irwin
TI Louis Lemberger In Memoriam
SO NEUROPSYCHOPHARMACOLOGY
LA English
DT Biographical-Item
C1 [Kopin, Irwin] NINDS, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
RP Kopin, I (reprint author), NINDS, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
EM kopinijk@aol.com
NR 1
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0893-133X
EI 1740-634X
J9 NEUROPSYCHOPHARMACOL
JI Neuropsychopharmacology
PD DEC
PY 2016
VL 41
IS 13
BP 3120
EP 3120
DI 10.1038/npp.2016.204
PG 1
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA EB7MC
UT WOS:000387570700022
PM 27818514
ER
PT J
AU Kalejaiye, A
Giri, N
Brewer, CC
Zalewski, CK
King, KA
Adams, CD
Rosenberg, PS
Kim, HJ
Alter, BP
AF Kalejaiye, Adedoyin
Giri, Neelam
Brewer, Carmen C.
Zalewski, Christopher K.
King, Kelly A.
Adams, Charleen D.
Rosenberg, Philip S.
Kim, H. Jeffrey
Alter, Blanche P.
TI Otologic manifestations of Fanconi anemia and other inherited bone
marrow failure syndromes
SO PEDIATRIC BLOOD & CANCER
LA English
DT Article
DE Fanconi anemia; hearing; IBMFS; otology
ID ABNORMALITIES; DIAGNOSIS; THERAPY; CANCER
AB BackgroundThe inherited bone marrow failure syndromes (IBMFSs) are diverse disorders with syndrome-specific features; their otologic and audiologic manifestations have not been well described. Our objective was to characterize these in patients with Fanconi anemia (FA), dyskeratosis congenita (DC), Diamond-Blackfan anemia (DBA), and Shwachman-Diamond syndrome (SDS), and to determine the association between physical findings and hearing loss.
MethodsPatients with an IBMFS underwent comprehensive clinical and laboratory evaluations and testing for syndrome-specific gene mutations. Hearing loss was measured by pure tone audiometry and otologic abnormalities by otomicroscopy.
ResultsPatients included 33 with FA, 37 with DC, 32 with DBA, and nine with SDS. Hearing loss was most frequent in patients with FA (45%) and DBA (14%). The most common type of hearing loss in FA was conductive (65%). Absent or hypoplastic radius, noted in 21% of the patients with FA, was associated with hearing loss in all cases. Otomicroscopy was abnormal in 66% of patients with FA. Characteristic ear abnormalities included small tympanic membrane (66%), malformed malleus (57%), aberrant tympanic bony island (48%), narrow external auditory canal (EAC) (32%), and abnormal course of chorda tympani (34%). Ear malformations were almost always associated with hearing loss. Hearing loss was rare in patients with DC and SDS.
ConclusionsFA is the major IBMFS with associated hearing loss, which is most commonly conductive. Radial hypoplasia or aplasia and characteristic congenital ear malformations are associated with hearing loss in patients with FA. Recognition of these syndrome-specific abnormalities should lead to earlier management of hearing loss.
C1 [Kalejaiye, Adedoyin] Howard Univ Hosp, Washington, DC USA.
[Giri, Neelam; Rosenberg, Philip S.; Alter, Blanche P.] NCI, NIH, Rockville, MD USA.
[Brewer, Carmen C.; Zalewski, Christopher K.; King, Kelly A.; Kim, H. Jeffrey] NIDCD, NIH, Bethesda, MD USA.
[Adams, Charleen D.] Univ Washington, Sch Publ Hlth, Seattle, WA 98195 USA.
[Kim, H. Jeffrey] Medstar Georgetown Univ Hosp, Washington, DC USA.
RP Giri, N (reprint author), 9609 Med Ctr Dr,Room 6E-538,MSC 9772, Bethesda, MD 20892 USA.
EM girin@mail.nih.gov
NR 21
TC 0
Z9 0
U1 1
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1545-5009
EI 1545-5017
J9 PEDIATR BLOOD CANCER
JI Pediatr. Blood Cancer
PD DEC
PY 2016
VL 63
IS 12
BP 2139
EP 2145
DI 10.1002/pbc.26155
PG 7
WC Oncology; Hematology; Pediatrics
SC Oncology; Hematology; Pediatrics
GA EB0HE
UT WOS:000387023900010
PM 27428025
ER
PT J
AU Schepers, SA
Haverman, L
Zadeh, S
Grootenhuis, MA
Wiener, L
AF Schepers, Sasja A.
Haverman, Lotte
Zadeh, Sima
Grootenhuis, Martha A.
Wiener, Lori
TI Healthcare Professionals' Preferences and Perceived Barriers for Routine
Assessment of Patient-Reported Outcomes in Pediatric Oncology Practice:
Moving Toward International Processes of Change
SO PEDIATRIC BLOOD & CANCER
LA English
DT Article
DE patient-reported outcomes; pediatric oncology; psychosocial; quality of
life
ID QUALITY-OF-LIFE; RANDOMIZED CONTROLLED-TRIAL; CLINICAL-PRACTICE;
SUPPORTIVE CARE; CANCER; CHILDREN; QUESTIONNAIRES; COMMUNICATION;
PERSPECTIVES; INFORMATION
AB BackgroundUsing patient-reported outcomes (PROs) in clinical practice has been shown to enhance detection of health-related quality of life problems and satisfaction with care in children with cancer. This study seeks to identify which PRO information healthcare professionals (HCPs) find useful and what the perceived barriers for routinely assessing PROs are.
ProcedureA total of 352 pediatric HCPs (43% male) from 52 countries completed a semistructured online 28-item questionnaire. Descriptive statistics (percentages) were used to identify highly important PRO information and perceived barriers. HCPs' perceived barriers were compared according to gender, years of work experience, and country using a Fishers exact test.
ResultsThe five highest ranked PRO topics relevant in routine assessment by HCPs were as follows: pain (98%), feeling sad or depressed (96%), overall physical symptoms (95%), problems with therapy adherence (94%), and overall emotional issues (93%). Five lowest ranked topics were as follows: difficulties praying (50%), other spiritual concerns (55, 56, and 60%), and feeling bored (60%). Barriers for assessing PROs included: time (58%), insufficient staff (49%), logistics (32%), and financial resources (26%). Providers from developing countries more often reported barriers concerning insufficient staff, logistics, and financial resources.
ConclusionsHCPs strongly value the use of physical and psychosocial PROs within pediatric oncology practice, but mainly perceive organizational barriers for routine assessment. To successfully integrate PROs, efforts should be made to address HCP-perceived barriers, such that patient-reported problems can be detected and timely referrals made.
C1 [Schepers, Sasja A.; Haverman, Lotte; Grootenhuis, Martha A.] Emma Childrens Hosp, Div Pediat, Psychosocial Dept, Acad Med Ctr, Post Box 22660, NL-110 0DD Amsterdam, Netherlands.
[Schepers, Sasja A.; Grootenhuis, Martha A.] Princess Maxima Ctr Pediat Oncol, Utrecht, Netherlands.
[Zadeh, Sima; Wiener, Lori] NCI, Behav Hlth Core, Pediat Psychosocial Support & Res Program, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Schepers, SA (reprint author), Emma Childrens Hosp, Div Pediat, Psychosocial Dept, Acad Med Ctr, Post Box 22660, NL-110 0DD Amsterdam, Netherlands.
EM s.a.schepers@amc.nl
NR 46
TC 0
Z9 0
U1 4
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1545-5009
EI 1545-5017
J9 PEDIATR BLOOD CANCER
JI Pediatr. Blood Cancer
PD DEC
PY 2016
VL 63
IS 12
BP 2181
EP 2188
DI 10.1002/pbc.26135
PG 8
WC Oncology; Hematology; Pediatrics
SC Oncology; Hematology; Pediatrics
GA EB0HE
UT WOS:000387023900016
PM 27511830
ER
PT J
AU Samala, R
Thorsheim, HR
Goda, S
Taskar, K
Gril, B
Steeg, PS
Smith, QR
AF Samala, Ramakrishna
Thorsheim, Helen R.
Goda, Satyanarayana
Taskar, Kunal
Gril, Brunilde
Steeg, Patricia S.
Smith, Quentin R.
TI Vinorelbine Delivery and Efficacy in the MDA-MB-231BR Preclinical Model
of Brain Metastases of Breast Cancer
SO PHARMACEUTICAL RESEARCH
LA English
DT Article
DE blood-brain barrier; brain metastases; breast cancer; permeability;
vinorelbine
ID CENTRAL-NERVOUS-SYSTEM; P-GLYCOPROTEIN; THERAPEUTIC TARGETS;
DRUG-DELIVERY; BARRIER; MICE; PERMEABILITY; RESISTANCE;
PHARMACOKINETICS; DISPOSITION
AB To evaluate vinorelbine drug exposure and activity in brain metastases of the human MDA-MB-231BR breast cancer model using integrated imaging and analysis.
Brain and systemic metastases were created by administration of cancer cells in female NuNu mice. After metastases developed, animals were administered vinorelbine at the maximal tolerated dose (12 mg/kg), and were evaluated thereafter for total and unbound drug pharmacokinetics, biomarker TUNEL staining, and barrier permeability to Texas red.
Median brain metastasis drug exposure was 4-fold greater than normal brain, yet only similar to 8% of non-barrier systemic metastases, which suggests restricted brain exposure. Unbound vinorelbine tissue/plasma partition coefficient, K-p,K-uu, equaled similar to 1.0 in systemic metastases, but 0.03-0.22 in brain metastases, documenting restricted equilibration. In select sub-regions of highest drug-uptake brain metastases, K-p,K-uu approached 1.0, indicating complete focal barrier breakdown. Most vinorelbine-treated brain metastases exhibited little or no positive early apoptosis TUNEL staining in vivo. The in vivo unbound vinorelbine IC50 for TUNEL-positive staining (56 nM) was 4-fold higher than that measured in vitro (14 nM). Consistent with this finding, P-glycoprotein expression was observed to be substantially upregulated in brain metastasis cells in vivo.
Vinorelbine exposure at maximum tolerated dose was less than one-tenth that in systemic metastases in > 70% of brain metastases, and was associated with negligible biomarker effect. In small subregions of the highest uptake brain metastases, compromise of blood-tumor barrier appeared complete. The results suggest that restricted delivery accounts for 80% of the compromise in drug efficacy for vinorelbine against this model.
C1 [Samala, Ramakrishna; Thorsheim, Helen R.; Goda, Satyanarayana; Taskar, Kunal; Smith, Quentin R.] Texas Tech Univ, Sch Pharm, Dept Pharmaceut Sci, Hlth Sci Ctr, 1300 South Coulter Dr, Amarillo, TX 79106 USA.
[Goda, Satyanarayana] Formurex Inc, Stockton, CA 95215 USA.
[Taskar, Kunal] GlaxoSmithKline, IVIVT, Mechanist Safety & Disposit, Ware SG12 0DP, Herts, England.
[Gril, Brunilde; Steeg, Patricia S.] NCI, Womens Malignancies Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Smith, QR (reprint author), Texas Tech Univ, Sch Pharm, Dept Pharmaceut Sci, Hlth Sci Ctr, 1300 South Coulter Dr, Amarillo, TX 79106 USA.
EM quentin.smith@ttuhsc.edu
FU Department of Defense Breast Cancer Program [W81XWH-06-2-0033]; Cancer
Prevention Research Institute of Texas [RP120489, RP110786]
FX This work was supported by grants from the Department of Defense Breast
Cancer Program (W81XWH-06-2-0033) and the Cancer Prevention Research
Institute of Texas (RP120489 and RP110786)
NR 49
TC 0
Z9 0
U1 6
U2 6
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0724-8741
EI 1573-904X
J9 PHARM RES-DORDR
JI Pharm. Res.
PD DEC
PY 2016
VL 33
IS 12
BP 2904
EP 2919
DI 10.1007/s11095-016-2012-3
PG 16
WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy
SC Chemistry; Pharmacology & Pharmacy
GA EB5DY
UT WOS:000387395000004
PM 27541873
ER
PT J
AU DeCherney, AH
Barnett, RL
AF DeCherney, Alan H.
Barnett, Rebecca L.
TI In Vitro Fertilization Research is Translational Research
SO REPRODUCTIVE SCIENCES
LA English
DT Article; Proceedings Paper
CT ART of Reproductive Medicine Symposium
CY FEB, 2016
CL SPAIN
DE IVF; translational research; evidence-based medicine; ART; in vitro
fertilization; assisted reproductive technologies
AB In vitro fertilization (IVF) is the perfect example of translational research. Changes in IVF and the IVF laboratory have been transmitted to clinical care, showing dramatic improvements in health outcomes, including notable increases in the cumulative pregnancy rate. Current research in the laboratory focusing on culture media, embryo selection criteria, and implementation of genetic testing and manipulation promises to translate to further improvements in our ability to assist human reproduction. The field of IVF and ART remains a large source for clinical and scientific discovery and development, and will require the proper interested and invested personnel, occupational structuring, and funding for continued success.
C1 [DeCherney, Alan H.] Natl Inst Child Hlth & Human Dev NICHD, Bethesda, MD USA.
[Barnett, Rebecca L.] Rutgers Robert Wood Johnson Med Sch, New Brunswick, NJ USA.
RP Barnett, RL (reprint author), 125 Paterson St, New Brunswick, NJ 08901 USA.
EM barnetrl@rutgers.edu
NR 7
TC 0
Z9 0
U1 4
U2 4
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1933-7191
EI 1933-7205
J9 REPROD SCI
JI Reprod. Sci.
PD DEC
PY 2016
VL 23
IS 12
BP 1634
EP 1638
DI 10.1177/1933719116667608
PG 5
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA EB6IE
UT WOS:000387484600006
PM 27821560
ER
PT J
AU Liu, BM
Yu, MD
Graubard, BI
Troiano, RP
Schenker, N
AF Liu, Benmei
Yu, Mandi
Graubard, Barry I.
Troiano, Richard P.
Schenker, Nathaniel
TI Multiple imputation of completely missing repeated measures data within
person from a complex sample: application to accelerometer data in the
National Health and Nutrition Examination Survey
SO STATISTICS IN MEDICINE
LA English
DT Article
DE accelerometer data; missing; primary sampling units; multiple
imputation; alternative conditional expectation models
ID PHYSICAL-ACTIVITY; METABOLIC SYNDROME; REGRESSION-MODELS; STEPPING
CADENCE; 2005-2006 NHANES; UNITED-STATES; TRANSFORMATIONS; STEPS/DAY;
PATTERNS; ADULTS
AB The Physical Activity Monitor component was introduced into the 2003-2004 National Health and Nutrition Examination Survey (NHANES) to collect objective information on physical activity including both movement intensity counts and ambulatory steps. Because of an error in the accelerometer device initialization process, the steps data were missing for all participants in several primary sampling units, typically a single county or group of contiguous counties, who had intensity count data from their accelerometers. To avoid potential bias and loss in efficiency in estimation and inference involving the steps data, we considered methods to accurately impute the missing values for steps collected in the 2003-2004 NHANES. The objective was to come up with an efficient imputation method that minimized model-based assumptions. We adopted a multiple imputation approach based on additive regression, bootstrapping and predictive mean matching methods. This method fits alternative conditional expectation (ace) models, which use an automated procedure to estimate optimal transformations for both the predictor and response variables. This paper describes the approaches used in this imputation and evaluates the methods by comparing the distributions of the original and the imputed data. A simulation study using the observed data is also conducted as part of the model diagnostics. Finally, some real data analyses are performed to compare the before and after imputation results. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.
C1 [Liu, Benmei; Yu, Mandi; Troiano, Richard P.] NCI, Div Canc Control & Populat Sci, Rockville, MD 20850 USA.
[Graubard, Barry I.] NCI, Div Canc Epidemiol & Genet, Rockville, MD USA.
[Schenker, Nathaniel] Ctr Dis Control & Prevent, Natl Ctr Hlth Stat, Hyattsville, MD 20782 USA.
RP Liu, BM (reprint author), NCI, Div Canc Control & Populat Sci, Rockville, MD 20850 USA.
EM liub2@mail.nih.gov
FU Intramural NIH HHS [Z99 CA999999]
NR 27
TC 0
Z9 0
U1 4
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0277-6715
EI 1097-0258
J9 STAT MED
JI Stat. Med.
PD DEC
PY 2016
VL 35
IS 28
BP 5170
EP 5188
DI 10.1002/sim.7049
PG 19
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 EB4PR
UT WOS:000387355100004
PM 27488606
ER
PT J
AU Shardell, M
Ferrucci, L
AF Shardell, Michelle
Ferrucci, Luigi
TI Instrumental variable analysis of multiplicative models with potentially
invalid instruments
SO STATISTICS IN MEDICINE
LA English
DT Article
DE causal inference; generalized method of moments; instrumental variables;
structural mean models
ID STRUCTURAL-NESTED MODELS; MENDELIAN RANDOMIZATION; CAUSAL INFERENCE;
MEAN MODELS; GENERALIZED-METHOD; OUTCOMES; EPIDEMIOLOGISTS;
IDENTIFICATION; MOMENTS; TRIALS
AB Instrumental variable (IV) methods have potential to consistently estimate the causal effect of an exposure on an outcome in the presence of unmeasured confounding. However, validity of IV methods relies on strong assumptions, some of which cannot be conclusively verified from observational data. One such assumption is that the effect of the proposed instrument on the outcome is completely mediated by the exposure. We consider the situation where this assumption is violated, but the remaining IV assumptions hold; that is, the proposed IV (1) is associated with the exposure and (2) has no unmeasured causes in common with the outcome. We propose a method to estimate multiplicative structural mean models of binary outcomes in this scenario in the presence of unmeasured confounding. We also extend the method to address multiple scenarios, including mediation analysis. The method adapts the asymptotically efficient G-estimation approach that was previously proposed for additive structural mean models, and it can be carried out using off-the-shelf software for generalized method of moments. Monte Carlo simulation studies show that the method has low bias and accurate coverage. We applied the method to a case study of circulating vitamin D and depressive symptoms using season of blood collection as a (potentially invalid) instrumental variable. Potential applications of the proposed method include randomized intervention studies as well as Mendelian randomization studies with genetic variants that affect multiple phenotypes, possibly including the outcome. Published 2016. This article is a U.S. Government work and is in the public domain in the USA
C1 [Shardell, Michelle; Ferrucci, Luigi] NIA, Harbor Hosp, Rm NM529,3001 S Hanover St, Baltimore, MD 21225 USA.
RP Shardell, M (reprint author), NIA, Harbor Hosp, Rm NM529,3001 S Hanover St, Baltimore, MD 21225 USA.
EM michelle.shardell@nih.gov
FU National Institute on Aging Intramural Program
FX The authors would like to thank National Institute on Aging Intramural
Program for funding this project.
NR 41
TC 0
Z9 0
U1 3
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0277-6715
EI 1097-0258
J9 STAT MED
JI Stat. Med.
PD DEC
PY 2016
VL 35
IS 29
BP 5430
EP 5447
DI 10.1002/sim.7069
PG 18
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 EB4QJ
UT WOS:000387357400008
PM 27527517
ER
PT J
AU Mitchell, EM
Plowden, TC
Schisterman, EF
AF Mitchell, Emily M.
Plowden, Torie C.
Schisterman, Enrique F.
TI Estimating relative risk of a log-transformed exposure measured in pools
SO STATISTICS IN MEDICINE
LA English
DT Article
DE biomarkers; design; log-transformation; pooled specimens; regression
calibration
ID ROC CURVE ANALYSIS; REGRESSION-MODELS; EFFICIENT DESIGN; BIOMARKER DATA;
NORMAL-WEIGHT; LEPTIN; SERUM; DISTRIBUTIONS; BIOSPECIMENS; SUBJECT
AB Pooling biospecimens prior to performing laboratory assays is a useful tool to reduce costs, achieve minimum volume requirements and mitigate assay measurement error. When estimating the risk of a continuous, pooled exposure on a binary outcome, specialized statistical techniques are required. Current methods include a regression calibration approach, where the expectation of the individual-level exposure is calculated by adjusting the observed pooled measurement with additional covariate data. While this method employs a linear regression calibration model, we propose an alternative model that can accommodate log-linear relationships between the exposure and predictive covariates. The proposed model permits direct estimation of the relative risk associated with a log-transformation of an exposure measured in pools. Published 2016. This article is a U.S. Government work and is in the public domain in the USA
C1 [Mitchell, Emily M.; Schisterman, Enrique F.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Intramural Populat Hlth Res, Bethesda, MD 20892 USA.
[Plowden, Torie C.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, Bethesda, MD 20892 USA.
RP Schisterman, EF (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Intramural Populat Hlth Res, Bethesda, MD 20892 USA.
EM schistee@mail.nih.gov
OI Schisterman, Enrique/0000-0003-3757-641X
FU Intramural Research Program of the Eunice Kennedy Shriver National
Institute of Child Health and Human Development, National Institutes of
Health; Long-Range Research Initiative of the American Chemistry Council
FX This research was supported by the Intramural Research Program of the
Eunice Kennedy Shriver National Institute of Child Health and Human
Development, National Institutes of Health, and by the Long-Range
Research Initiative of the American Chemistry Council.
NR 47
TC 0
Z9 0
U1 1
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0277-6715
EI 1097-0258
J9 STAT MED
JI Stat. Med.
PD DEC
PY 2016
VL 35
IS 29
BP 5477
EP 5494
DI 10.1002/sim.7075
PG 18
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 EB4QJ
UT WOS:000387357400011
PM 27530506
ER
PT J
AU Xu, ZZ
Proschan, M
Lee, S
AF Xu, Zhenzhen
Proschan, Michael
Lee, Shiowjen
TI Validity and power considerations on hypothesis testing under
minimization
SO STATISTICS IN MEDICINE
LA English
DT Editorial Material
C1 [Xu, Zhenzhen; Lee, Shiowjen] US FDA, Ctr Biol Evaluat & Res, Silver Spring, MD 20993 USA.
[Proschan, Michael] NIAID, Biostat Res Branch, 9000 Rockville Pike, Bethesda, MD 20892 USA.
RP Xu, ZZ (reprint author), US FDA, Ctr Biol Evaluat & Res, Silver Spring, MD 20993 USA.
EM zhenzhen.xu@fda.hhs.gov
NR 5
TC 0
Z9 0
U1 3
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0277-6715
EI 1097-0258
J9 STAT MED
JI Stat. Med.
PD DEC
PY 2016
VL 35
IS 29
BP 5527
EP 5528
DI 10.1002/sim.7037
PG 2
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 EB4QJ
UT WOS:000387357400015
PM 27870128
ER
PT J
AU Yamada, D
Iyoda, T
Vizcardo, R
Shimizu, K
Sato, Y
Endo, TA
Kitahara, G
Okoshi, M
Kobayashi, M
Sakurai, M
Ohara, O
Taniguchi, M
Koseki, H
Fujii, SI
AF Yamada, Daisuke
Iyoda, Tomonori
Vizcardo, Raul
Shimizu, Kanako
Sato, Yusuke
Endo, Takaho A.
Kitahara, Genta
Okoshi, Momoko
Kobayashi, Midori
Sakurai, Maki
Ohara, Osamu
Taniguchi, Masaru
Koseki, Haruhiko
Fujii, Shin-Ichiro
TI Efficient Regeneration of Human V alpha 24(+) Invariant Natural Killer T
Cells and Their Anti-Tumor Activity In Vivo
SO STEM CELLS
LA English
DT Article
DE Invariant NKT cells; NK cells; Induced pluripotent stem cells;
Reprogramming; Immunotherapy
ID PLURIPOTENT STEM-CELLS; ACTIVATE NK CELLS; ALPHA-GALACTOSYLCERAMIDE;
DENDRITIC CELLS; LUNG-CANCER; PHASE-I; INNATE; CYTOTOXICITY; GENERATION;
IMMUNITY
AB Reprogramming of antigen-specific T lymphocytes into induced pluripotent stem cells (iPSCs) and their subsequent re-differentiation has enabled expansion of functional T lymphocytes in vitro, thus opening up new approaches for immunotherapy of cancer and other diseases. In this study, we have established a robust protocol to reprogram human invariant NKT (V alpha 24(+) iNKT) cells, which have been shown to act as cellular adjuvants and thus exert anti-tumor activity in mice and humans, and to re-differentiate the iNKT cell-derived iPSCs into functional iNKT cells. These iPSC-derived iNKT cells (iPS-V alpha 24(+) iNKT cells) can be activated by ligand-pulsed dendritic cells (DCs) and produce a large amount of interferon-c upon activation, as much as parental V alpha 24(+) iNKT cells, but exhibit even better cytotoxic activity against various tumor cell lines. The iPS-V alpha 24(+) iNKT cells possess significant anti-tumor activity in tumor-bearing mice and can activate autologous NK cells upon activation by ligand-pulsed DCs in the NOG mouse model in vivo, further extending their therapeutic potential. This study thus provides a first proof of concept for the clinical application of human iPS-V alpha 24(+) iNKT cells for cancer immunotherapy.
C1 [Yamada, Daisuke; Vizcardo, Raul; Kitahara, Genta; Okoshi, Momoko; Kobayashi, Midori; Koseki, Haruhiko] RIKEN Ctr Integrat Med Sci IMS, Lab Dev Genet, Yokohama, Kanagawa, Japan.
[Iyoda, Tomonori; Shimizu, Kanako; Sato, Yusuke; Sakurai, Maki; Fujii, Shin-Ichiro] RIKEN Ctr Integrat Med Sci IMS, Lab Immunotherapy, Yokohama, Kanagawa, Japan.
[Endo, Takaho A.; Ohara, Osamu] RIKEN Ctr Integrat Med Sci IMS, Lab Integrat Genom, Yokohama, Kanagawa, Japan.
[Taniguchi, Masaru] RIKEN Ctr Integrat Med Sci IMS, Lab Immunoregulat, Yokohama, Kanagawa, Japan.
[Vizcardo, Raul] NCI, Surg Branch, NIH, Bldg 10, Bethesda, MD 20892 USA.
RP Fujii, SI (reprint author), RIKEN Ctr Integrat Med Sci IMS, Lab Immunotherapy, Tsurumi Ku, 1-7-22 Suehiro Cho, Yokohama, Kanagawa 2300045, Japan.; Koseki, H (reprint author), RIKEN IMS, Lab Dev Genet, Tsurumi Ku, 1-7-22 Suehiro Cho, Yokohama, Kanagawa 2300045, Japan.
EM haruhiko.koseki@riken.jp; shin-ichiro.fujii@riken.jp
RI Endo, Takaho/B-5763-2017
OI Endo, Takaho/0000-0002-2801-2463
FU Research Center Network for Realization of Regenerative Medicine from
Japan Agency for Medical Research and Development (AMED); CREST, Japan
Science and Technology Agency
FX We are grateful to prof. P.D. Burrows for the critical reading of the
manuscript. We thank Masami Kawamura and Chieko Tezuka for their
technical supports. This work was supported by the Research Center
Network for Realization of Regenerative Medicine from Japan Agency for
Medical Research and Development (AMED) and CREST, Japan Science and
Technology Agency.
NR 32
TC 1
Z9 1
U1 6
U2 6
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1066-5099
EI 1549-4918
J9 STEM CELLS
JI Stem Cells
PD DEC
PY 2016
VL 34
IS 12
BP 2852
EP 2860
DI 10.1002/stem.2465
PG 9
WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology;
Oncology; Cell Biology; Hematology
SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology
GA EB4NE
UT WOS:000387347800005
PM 27422351
ER
PT J
AU Perosky, JE
Khoury, BM
Jenks, TN
Ward, FS
Cortright, K
Meyer, B
Barton, DK
Sinder, BP
Marini, JC
Caird, MS
Kozloff, KM
AF Perosky, Joseph E.
Khoury, Basma M.
Jenks, Terese N.
Ward, Ferrous S.
Cortright, Kai
Meyer, Bethany
Barton, David K.
Sinder, Benjamin P.
Marini, Joan C.
Caird, Michelle S.
Kozloff, Kenneth M.
TI Single dose of bisphosphonate preserves gains in bone mass following
cessation of sclerostin antibody in Brtl/ plus osteogenesis imperfecta
model
SO BONE
LA English
DT Article
DE Osteogenesis imperfecta; Sclerostin antibody; Cessation; Bisphosphonate;
Osteoporosis
ID MOUSE MODEL; POSTMENOPAUSAL WOMEN; ALENDRONATE TREATMENT; MINERAL
DENSITY; TERIPARATIDE TREATMENT; OVARIECTOMIZED RATS; IN-VIVO; STRENGTH;
OSTEOPOROSIS; INCREASES
AB Sclerostin antibody has demonstrated a bone-forming effect in pre-clinical models of osteogenesis imperfecta, where mutations in collagen or collagen-associated proteins often result in high bone fragility in pediatric patients. Cessation studies in osteoporotic patients have demonstrated that sclerostin antibody, like intermittent PTH treatment, requires sequential anti-resorptive therapy to preserve the anabolic effects in adult populations. However, the persistence of anabolic gains from either drug has not been explored clinically in 01, or in any animal model. To determine whether cessation of sclerostin antibody therapy in a growing OI skeleton requires sequential anti-resorptive treatment to preserve anabolic gains in bone mass, we treated 3 week old Brtl/+ and wild type mice for 5 weeks with SclAb, and then withdrew treatment for an additional 6 weeks. Trabecular bone loss was evident following cessation, but was preserved in a dose-dependent manner with single administration of pamidronate at the time of cessation. In vivo longitudinal near-infrared optical imaging of cathepsin K activation in the proximal tibia suggests an anti-resorptive effect of both SclAb and pamidronate which is reversed after three weeks of cessation. Cortical bone was considerably less susceptible to cessation effects, and showed no structural or functional deficits in the absence of pamidronate during this cessation period. In conclusion, while SclAb induces a considerable anabolic gain in the rapidly growing Brtl+ murine model of 01, a single sequential dose of antiresorptive drug is required to maintain bone mass at trabecular sites for 6 weeks following cessation. (C) 2016 Elsevier Inc. All rights reserved.
C1 [Perosky, Joseph E.; Khoury, Basma M.; Jenks, Terese N.; Ward, Ferrous S.; Cortright, Kai; Meyer, Bethany; Barton, David K.; Sinder, Benjamin P.; Caird, Michelle S.; Kozloff, Kenneth M.] Univ Michigan, Dept Orthopaed Surg, Ann Arbor, MI 48109 USA.
[Jenks, Terese N.; Ward, Ferrous S.; Cortright, Kai; Meyer, Bethany; Barton, David K.; Sinder, Benjamin P.; Kozloff, Kenneth M.] Univ Michigan, Dept Biomed Engn, Ann Arbor, MI 48109 USA.
[Marini, Joan C.] NICHHD, Bone & Extracellular Matrix Branch, NIH, Bethesda, MD 20892 USA.
RP Kozloff, KM (reprint author), 2015 Biomed Sci Res Bldg,109 Zina Pitcher Pl, Ann Arbor, MI 48109 USA.
EM kenkoz@umich.edu
FU NIH [AR062522]
FX This study was supported by NIH grant AR062522. SclAb was graciously
provided by Amgen and UCB. The authors thank Mike Ominsky for feedback
on the data and critical review of the manuscript. The authors would
like to thank Bonnie Nolan and Kathy Sweet for their technical
assistance. Study designed and conducted by KMK, JEP, and MSC. Data
collected by JEP, DKB, and BK. Data analyzed and interpreted by all
authors. Manuscript was written and approved by all authors. KMK takes
responsibility for the integrity of the data analysis.
NR 47
TC 0
Z9 0
U1 5
U2 5
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 8756-3282
EI 1873-2763
J9 BONE
JI Bone
PD DEC
PY 2016
VL 93
BP 79
EP 85
DI 10.1016/j.bone.2016.09.013
PG 7
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA EA9TL
UT WOS:000386987500009
PM 27641475
ER
PT J
AU Marcoline, FV
Ishida, Y
Mindell, JA
Nayak, S
Grabe, M
AF Marcoline, Frank V.
Ishida, Yoichi
Mindell, Joseph A.
Nayak, Smita
Grabe, Michael
TI A mathematical model of osteoclast acidification during bone resorption
SO BONE
LA English
DT Article
DE Osteoclast; Mathematical model; Acidification; V-ATPase; CIC-7; H(v)1
ID GATED PROTON CHANNELS; CHLORIDE BICARBONATE EXCHANGE; INTRACELLULAR PH
REGULATION; RAT-LIVER LYSOSOMES; RUFFLED BORDER; POSTMENOPAUSAL
OSTEOPOROSIS; RESORBING OSTEOCLASTS; NA+/H+ ANTIPORTER; AVIAN
OSTEOCLAST; PLASMA-MEMBRANE
AB Bone resorption by osteoclasts occurs through the creation of a sealed extracellular compartment (ECC), or pit, adjacent to the bone that is subsequently acidified through a complex biological process. The low pH of the pit dissolves the bone mineral and activates acid proteases that further break down the bone matrix. There are many ion channels, transporters, and soluble proteins involved in osteoclast mediated resorption, and in the past few years, there has been an increased understanding of the identity and properties of some key proteins such as the CIC-7 CI-/H+ antiporter and the H(v)1 proton channel. Here we present a detailed mathematical model of osteoclast acidification that includes the influence of many of the key regulatory proteins. The primary enzyme responsible for acidification is the vacuolar H+-ATPase (V-ATPase), which pumps protons from the cytoplasm into the pit Unlike the acidification of small lysosomes, the pit is so large that protons become depleted from the cytoplasm. Hence, proton buffering and production in the cytoplasm by carbonic anhydrase II (CAII) is potentially important for proper acidification. We employ an ordinary differential equations (ODE)-based model that accounts for the changes in ionic species in the cytoplasm and the resorptive pit. Additionally, our model tracks ionic flow between the cytoplasm and the extracellular solution surrounding the cell. Whenever possible, the properties of individual channels and transporters are calibrated based on electrophysiological measurements, and physical properties of the cell, such as buffering capacity, surface areas, and volumes, are estimated based on available data. Our model reproduces many of the experimental findings regarding the role of key proteins in the acidification process, and it allows us to estimate, among other things, number of active pumps, protons moved, and the influence of particular mutations implicated in disease. (C) 2016 Elsevier Inc All rights reserved.
C1 [Marcoline, Frank V.; Grabe, Michael] Univ Calif San Francisco, Cardiovasc Res Inst, San Francisco, CA 94158 USA.
[Marcoline, Frank V.; Grabe, Michael] Univ Calif San Francisco, Dept Pharmaceut Chem, San Francisco, CA 94158 USA.
[Ishida, Yoichi] Ohio Univ, Dept Philosophy, Athens, OH 45701 USA.
[Mindell, Joseph A.] NINDS, Membrane Transport Biophys Unit, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
[Nayak, Smita] Swedish Hlth Serv, Swedish Ctr Res & Innovat, Seattle, WA 98122 USA.
RP Grabe, M (reprint author), Univ Calif San Francisco, Cardiovasc Res Inst, San Francisco, CA 94158 USA.
EM michael.grabe@ucsf.edu
FU National Institutes of Health [R21-GM100224]
FX We would like to thank Thomas DeCoursey, Mary Nakamura, Seth Alper,
Diane Barber, Lily Jan, and Neville Bethel for useful discussions. We
thank Jianmin Sun for his help early in this study writing the first
version of the ODE solver in Matlab (TM). Additionally, we acknowledge
Benjamin Hsieh's early help on this study. This work was supported by
National Institutes of Health Grant (R21-GM100224).
NR 84
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 8756-3282
EI 1873-2763
J9 BONE
JI Bone
PD DEC
PY 2016
VL 93
BP 167
EP 180
DI 10.1016/j.bone.2016.09.007
PG 14
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA EA9TL
UT WOS:000386987500018
PM 27650914
ER
PT J
AU Welsh, KJ
Soldin, SJ
AF Welsh, Kerry J.
Soldin, Steven J.
TI How reliable are free thyroid and total T-3 hormone assays?
SO EUROPEAN JOURNAL OF ENDOCRINOLOGY
LA English
DT Review
ID TANDEM MASS-SPECTROMETRY; FREE-THYROXINE; SUBCLINICAL HYPOTHYROIDISM;
FREE TRIIODOTHYRONINE; NONTHYROIDAL ILLNESS; STIMULATING HORMONE;
IMMUNOASSAYS; ASSOCIATION; DISEASE; BINDING
AB Hypothyroidism is a very common disorder worldwide, for which the usual treatment is monotherapy with levothyroxine (L=T-4). However, a number of patients treated with L=T-4 continue to report symptoms of hypothyroidism despite seemingly normal levels of thyroid-stimulating hormone (TSH), free-T-3 (FT3) and free-T-4 (FT4) measured by immunoassay. This review summarizes the limitations of the immunoassays commonly used to measure thyroid hormone levels and emphasizes the advantages of the role of liquid chromatography-tandem mass spectrometry (LC-MS/MS). Immunoassays for free thyroid hormone are affected by alterations in serum binding proteins that occur in many physiological and disease states. Multiple studies show falsely normal values for T-3, FT3 and FT4 by immunoassay that are below the reference interval when measured by (ultrafiltration) LC-MS/MS, a reference method. We suggest evaluation of thyroid hormone levels by ultrafiltration LC-MS/MS for patients who continue to experience hypothyroid symptoms on LT-4. This may help identify the approximately 20% subset of patients who would benefit from addition of T-3 to their treatment regimen (combination therapy).
C1 [Welsh, Kerry J.; Soldin, Steven J.] NIH, Div Clin Chem, Dept Lab Med, Bldg 10, Bethesda, MD 20892 USA.
RP Soldin, SJ (reprint author), NIH, Div Clin Chem, Dept Lab Med, Bldg 10, Bethesda, MD 20892 USA.
EM steven.soldin@nih.gov
FU National Institutes of Health Intramural Research Award
FX The authors are supported by the National Institutes of Health
Intramural Research Award.
NR 55
TC 0
Z9 0
U1 12
U2 12
PU BIOSCIENTIFICA LTD
PI BRISTOL
PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT,
ENGLAND
SN 0804-4643
EI 1479-683X
J9 EUR J ENDOCRINOL
JI Eur. J. Endocrinol.
PD DEC
PY 2016
VL 175
IS 6
BP R255
EP R263
DI 10.1530/EJE-16-0193
PG 9
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA EA8UV
UT WOS:000386915600003
PM 27737898
ER
PT J
AU Leyva, B
Persoskie, A
Ottenbacher, A
Hamilton, JG
Allen, JD
Kobrin, SC
Taplin, SH
AF Leyva, Bryan
Persoskie, Alexander
Ottenbacher, Allison
Hamilton, Jada G.
Allen, Jennifer D.
Kobrin, Sarah C.
Taplin, Stephen H.
TI Do Men Receive Information Required for Shared Decision Making About PSA
Testing? Results from a National Survey
SO JOURNAL OF CANCER EDUCATION
LA English
DT Article
DE Shared decision making; PSA testing; Prostate cancer screening;
Uncertainty; Patient-provider communication
ID PROSTATE-SPECIFIC ANTIGEN; HEALTH-PROFESSIONALS PERCEPTIONS;
AMERICAN-CANCER-SOCIETY; CARE PHYSICIANS USE; CLINICAL-PRACTICE;
RANDOMIZED PROSTATE; SCREENING DECISIONS; SELF-REPORTS; FOLLOW-UP;
GUIDELINES
AB Most professional organizations, including the American College of Physicians and U.S. Preventive Services Task Force, emphasize that screening for prostate cancer with the prostate-specific antigen (PSA) test should only occur after a detailed discussion between the health-care provider and patient about the known risks and potential benefits of the test. In fact, guidelines strongly advise health-care providers to involve patients, particularly those at elevated risk of prostate cancer, in a "shared decision making" (SDM) process about PSA testing. We analyzed data from the National Cancer Institute's Health Information National Trends Survey 2011-2012-a nationally representative, cross-sectional survey-to examine the extent to which health professionals provided men with information critical to SDM prior to PSA testing, including (1) that patients had a choice about whether or not to undergo PSA testing, (2) that not all doctors recommend PSA testing, and (3) that no one is sure if PSA testing saves lives. Over half (55 %) of men between the ages of 50 and 74 reported ever having had a PSA test. However, only 10 % of men, regardless of screening status, reported receiving all three pieces of information: 55 % reported being informed that they could choose whether or not to undergo testing, 22 % reported being informed that some doctors recommend PSA testing and others do not, and 14 % reported being informed that no one is sure if PSA testing actually saves lives. Black men and men with lower levels of education were less likely to be provided this information. There is a need to improve patient-provider communication about the uncertainties associated with the PSA test. Interventions directed at patients, providers, and practice settings should be considered.
C1 [Leyva, Bryan; Kobrin, Sarah C.; Taplin, Stephen H.] NCI, Proc Care Res Branch, Behav Res Program, NIH, 9609 Med Ctr Dr 3E230, Bethesda, MD 20892 USA.
[Persoskie, Alexander] NCI, Basic Biobehav & Psychol Sci Branch, Behav Res Program, NIH, Bethesda, MD 20892 USA.
[Ottenbacher, Allison] NCI, Sci Res & Technol Branch, Behav Res Program, NIH, Bethesda, MD 20892 USA.
[Hamilton, Jada G.] Mem Sloan Kettering Canc Ctr, Dept Psychiat & Behav Sci, 1275 York Ave, New York, NY 10021 USA.
[Allen, Jennifer D.] Tufts Univ, Dept Publ Hlth & Community Med, Boston, MA 02111 USA.
RP Leyva, B (reprint author), NCI, Proc Care Res Branch, Behav Res Program, NIH, 9609 Med Ctr Dr 3E230, Bethesda, MD 20892 USA.
EM leyvabryan@gmail.com
OI Ottenbacher, Allison/0000-0002-8974-5580
NR 60
TC 1
Z9 1
U1 2
U2 2
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0885-8195
EI 1543-0154
J9 J CANCER EDUC
JI J. Cancer Educ.
PD DEC
PY 2016
VL 31
IS 4
BP 693
EP 701
DI 10.1007/s13187-015-0870-8
PG 9
WC Oncology; Education, Scientific Disciplines; Public, Environmental &
Occupational Health
SC Oncology; Education & Educational Research; Public, Environmental &
Occupational Health
GA EA5OA
UT WOS:000386669200014
PM 26498649
ER
PT J
AU Commodore-Mensah, Y
Sampah, M
Berko, C
Cudjoe, J
Abu-Bonsrah, N
Obisesan, O
Agyemang, C
Adeyemo, A
Himmelfarb, CD
AF Commodore-Mensah, Yvonne
Sampah, Maame
Berko, Charles
Cudjoe, Joycelyn
Abu-Bonsrah, Nancy
Obisesan, Olawunmi
Agyemang, Charles
Adeyemo, Adebowale
Himmelfarb, Cheryl Dennison
TI The Afro-Cardiac Study: Cardiovascular Disease Risk and Acculturation in
West African Immigrants in the United States: Rationale and Study Design
SO JOURNAL OF IMMIGRANT AND MINORITY HEALTH
LA English
DT Article
DE African immigrants; Cardiovascular disease; Immigrants; Acculturation
ID AMERICAN-HEART-ASSOCIATION; HIGH BLOOD-PRESSURE; PSYCHOLOGICAL
ACCULTURATION; EPIDEMIOLOGIC TRANSITION; POPULATION-CHANGE; NATIONAL
SAMPLE; PREVALENCE; HEALTH; HYPERTENSION; OBESITY
AB Cardiovascular disease (CVD) remains the leading cause of death in the United States (US). African-descent populations bear a disproportionate burden of CVD risk factors. With the increase in the number of West African immigrants (WAIs) to the US over the past decades, it is imperative to specifically study this new and substantial subset of the African-descent population and how acculturation impacts their CVD risk. The Afro-Cardiac study, a community-based cross-sectional study of adult WAIs in the Baltimore-Washington metropolis. Guided by the PRECEDE-PROCEED model, we used a modification of the World Health Organization Steps survey to collect data on demographics, socioeconomic status, migration-related factors and behaviors. We obtained physical, biochemical, acculturation measurements as well as a socio-demographic and health history. Our study provides critical data on the CVD risk of WAIs. The framework used is valuable for future epidemiological studies addressing CVD risk and acculturation among immigrants.
C1 [Commodore-Mensah, Yvonne] Emory Univ, Nell Hodgson Woodruff Sch Nursing, 1520 Clifton Rd NE,Rm 368, Atlanta, GA 30322 USA.
[Sampah, Maame; Abu-Bonsrah, Nancy] Johns Hopkins Sch Med, 733 N Broadway, Baltimore, MD 21205 USA.
[Berko, Charles] St Agnes Hosp, Dept Internal Med, 900 S Caton Ave, Baltimore, MD 21229 USA.
[Cudjoe, Joycelyn; Himmelfarb, Cheryl Dennison] Johns Hopkins Sch Nursing, 525 N Wolfe St, Baltimore, MD 21205 USA.
[Obisesan, Olawunmi] AT Still Univ, 800 W Jefferson St, Kirksville, MO 63501 USA.
[Agyemang, Charles] Univ Amsterdam, Amsterdam Med Ctr, Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands.
[Adeyemo, Adebowale] NHGRI, Ctr Res Genom & Global Hlth, Bldg 12A,Room 4047,12 South Dr,MSC 5635, Bethesda, MD 20892 USA.
RP Commodore-Mensah, Y (reprint author), Emory Univ, Nell Hodgson Woodruff Sch Nursing, 1520 Clifton Rd NE,Rm 368, Atlanta, GA 30322 USA.
EM ycommod@emory.edu
FU National Institute of Nursing Research (NINR) [1P30NR011409]
FX This study was supported by pilot funding from National Institute of
Nursing Research (NINR) [1P30NR011409]. We would like to acknowledge all
the research assistants (Felicia Sam, Grace Onayiga, Kojo Amoakwah,
Audrey Addaquay-Corey, Selase Agudu-Morgan, Loretta Odro and Jonathan
Aboagye) who participated in data collection as well as the leaders of
the community-based organized organizations that allowed data collection
to occur on their premises. Finally, we thank the study participants who
dedicated their time to advance our understanding of CVD risk among
WAIs.
NR 61
TC 0
Z9 0
U1 10
U2 10
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1557-1912
EI 1557-1920
J9 J IMMIGR MINOR HEALT
JI J. Immigr. Minor. Health
PD DEC
PY 2016
VL 18
IS 6
BP 1301
EP 1308
DI 10.1007/s10903-015-0291-0
PG 8
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA EA3JY
UT WOS:000386499600006
PM 26429573
ER
PT J
AU Varshney, GK
Carrington, B
Pei, WH
Bishop, K
Chen, ZL
Fan, CX
Xu, LS
Jones, M
LaFave, MC
Ledin, J
Sood, R
Burgess, SM
AF Varshney, Gaurav K.
Carrington, Blake
Pei, Wuhong
Bishop, Kevin
Chen, Zelin
Fan, Chunxin
Xu, Lisha
Jones, Marypat
LaFave, Matthew C.
Ledin, Johan
Sood, Raman
Burgess, Shawn M.
TI A high-throughput functional genomics workflow based on
CRISPR/Cas9-mediated targeted mutagenesis in zebrafish
SO NATURE PROTOCOLS
LA English
DT Article
ID ZINC-FINGER NUCLEASES; GENE-FUNCTION; IN-VIVO; SYSTEM; CRISPR-CAS9;
SPECIFICITY; WIDE; CAS9; RESOURCE; SEQUENCE
AB The zebrafish is a popular model organism for studying development and disease, and genetically modified zebrafish provide an essential tool for functional genomic studies. Numerous publications have demonstrated the efficacy of gene targeting in zebrafish using CRISPR/Cas9, and they have included descriptions of a variety of tools and methods for guide RNA synthesis and mutant identification. However, most of the published techniques are not readily scalable to increase throughput. We recently described a CRISPR/Cas9-based high-throughput mutagenesis and phenotyping pipeline in zebrafish. Here, we present a complete workflow for this pipeline, including target selection; cloning-free single-guide RNA (sgRNA) synthesis; microinjection; validation of the target-specific activity of the sgRNAs; founder screening to identify germline-transmitting mutations by fluorescence PCR; determination of the exact lesion by Sanger or next-generation sequencing (including software for analysis); and genotyping in the F-1 or subsequent generations. Using these methods, sgRNAs can be evaluated in 3 d, zebrafish germline-transmitting mutations can be identified within 3 months and stable lines can be established within 6 months. Realistically, two researchers can target tens to hundreds of genes per year using this protocol.
C1 [Varshney, Gaurav K.; Pei, Wuhong; Chen, Zelin; Xu, Lisha; LaFave, Matthew C.; Burgess, Shawn M.] NHGRI, Dev Genom Sect, Translat & Funct Genom Branch, NIH, Bethesda, MD 20892 USA.
[Varshney, Gaurav K.] Oklahoma Med Res Fdn, Funct & Chem Genom Program, 825 NE 13th St, Oklahoma City, OK 73104 USA.
[Carrington, Blake; Bishop, Kevin; Sood, Raman] NHGRI, Zebrafish Core, Translat & Funct Genom Branch, NIH, Bethesda, MD 20892 USA.
[Fan, Chunxin] Shanghai Ocean Univ, Minist Educ, Key Lab Explorat & Utilizat Aquat Genet Resource, Shanghai, Peoples R China.
[Jones, Marypat] NHGRI, Canc Genet & Comparat Genom Branch, NIH, Bethesda, MD 20892 USA.
[Ledin, Johan] Uppsala Univ, Sci Life Lab, Dept Organismal Biol, Uppsala, Sweden.
[LaFave, Matthew C.] Synthet Genom, San Diego, CA USA.
RP Burgess, SM (reprint author), NHGRI, Dev Genom Sect, Translat & Funct Genom Branch, NIH, Bethesda, MD 20892 USA.
EM burgess@mail.nih.gov
OI LaFave, Matthew/0000-0001-9165-041X; Varshney, Gaurav
K./0000-0002-0429-1904
FU Intramural Research Program of the National Human Genome Research
Institute; National Institutes of Health
FX We thank J. Fekecs and U. Harper for help with figures, and D. Prebilic,
H. Mahon and other staff of the National Institutes of Health zebrafish
facility for excellent animal care. This research is funded by the
Intramural Research Program of the National Human Genome Research
Institute; National Institutes of Health (S.M.B. and R.S.).
NR 34
TC 0
Z9 0
U1 36
U2 36
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1754-2189
EI 1750-2799
J9 NAT PROTOC
JI Nat. Protoc.
PD DEC
PY 2016
VL 11
IS 12
BP 2357
EP 2375
DI 10.1038/nprot.2016.141
PG 19
WC Biochemical Research Methods
SC Biochemistry & Molecular Biology
GA EA9PR
UT WOS:000386976800004
PM 27809318
ER
PT J
AU Lauritzen, KH
Hasan-Olive, MM
Regnell, CE
Kleppa, L
Scheibye-Knudsen, M
Gjedde, A
Klungland, A
Bohr, VA
Storm-Mathisen, J
Bergersen, LH
AF Lauritzen, Knut H.
Hasan-Olive, Md Mahdi
Regnell, Christine E.
Kleppa, Liv
Scheibye-Knudsen, Morten
Gjedde, Albert
Klungland, Arne
Bohr, Vilhelm A.
Storm-Mathisen, Jon
Bergersen, Linda H.
TI A ketogenic diet accelerates neurodegeneration in mice with induced
mitochondrial DNA toxicity in the forebrain
SO NEUROBIOLOGY OF AGING
LA English
DT Article
DE MtDNA damage; Ketogenic diet; Biogenesis; Neurodegeneration
ID TEMPORAL-LOBE EPILEPSY; ALZHEIMERS-DISEASE; KETONE-BODIES; BRAIN CANCER;
MOUSE-BRAIN; HUMAN-CELLS; DYNAMICS; POLYMERASE; PROTEINS; INFLAMMATION
AB Mitochondrial genome maintenance plays a central role in preserving brain health. We previously demonstrated accumulation of mitochondrial DNA damage and severe neurodegeneration in transgenic mice inducibly expressing a mutated mitochondrial DNA repair enzyme (mutUNG1) selectively in forebrain neurons. Here, we examine whether severe neurodegeneration in mutUNG1-expressing mice could be rescued by feeding the mice a ketogenic diet, which is known to have beneficial effects in several neurological disorders. The diet increased the levels of superoxide dismutase 2, and mitochondrial mass, enzymes, and regulators such as SIRT1 and FIS1, and appeared to downregulate N-methyl-Daspartic acid (NMDA) receptor subunits NR2A/B and upregulate gamma-aminobutyric acid A (GABA(A)) receptor subunits alpha(1). However, unexpectedly, the ketogenic diet aggravated neurodegeneration and mitochondrial deterioration. Electron microscopy showed structurally impaired mitochondria accumulating in neuronal perikarya. We propose that aggravation is caused by increased mitochondrial biogenesis of generally dysfunctional mitochondria. This study thereby questions the dogma that a ketogenic diet is unambiguously beneficial in mitochondrial disorders. (C) 2016 Elsevier Inc. All rights reserved.
C1 [Lauritzen, Knut H.; Hasan-Olive, Md Mahdi; Regnell, Christine E.; Kleppa, Liv; Storm-Mathisen, Jon; Bergersen, Linda H.] Univ Oslo, Synapt Neurochem Lab, Div Anat, Oslo, Norway.
[Lauritzen, Knut H.; Hasan-Olive, Md Mahdi; Regnell, Christine E.; Kleppa, Liv; Storm-Mathisen, Jon; Bergersen, Linda H.] Univ Oslo, CMBN SERTA Hlth Brain Ageing Ctr, Inst Basic Med Sci, Oslo, Norway.
[Lauritzen, Knut H.; Hasan-Olive, Md Mahdi; Regnell, Christine E.; Kleppa, Liv; Bergersen, Linda H.] Univ Oslo, Inst Oral Biol, Brain & Muscle Energy Grp, Electron Microscopy Lab, Oslo, Norway.
[Regnell, Christine E.; Gjedde, Albert; Bergersen, Linda H.] Univ Copenhagen, Fac Hlth Sci, Ctr Hlth Aging, Copenhagen, Denmark.
[Regnell, Christine E.; Gjedde, Albert; Bergersen, Linda H.] Univ Copenhagen, Fac Hlth Sci, Dept Neurosci & Pharmacol, Copenhagen, Denmark.
[Scheibye-Knudsen, Morten; Bohr, Vilhelm A.] NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA.
[Klungland, Arne] Oslo Univ Hosp, Inst Med Microbiol, Oslo, Norway.
[Klungland, Arne] Univ Oslo, Oslo, Norway.
[Klungland, Arne] Univ Oslo, Inst Basic Med Sci, Dept Mol Med, Oslo, Norway.
RP Bergersen, LH (reprint author), Univ Oslo, Div Anat, N-0317 Oslo, Norway.; Bergersen, LH (reprint author), Univ Oslo, CMBN SERTA Hlth Brain Ageing Ctr, N-0317 Oslo, Norway.
EM l.h.bergersen@odont.uio.no
OI Scheibye-Knudsen, Morten/0000-0002-6637-1280; Gjedde,
Albert/0000-0002-3756-7401
FU Research Council of Norway; Norwegian Health Association; Lundbeck
Foundation (Denmark); South-Eastern Norway Regional Health Authority
FX This study was supported by research grants from The Research Council of
Norway, the Norwegian Health Association, The Lundbeck Foundation
(Denmark), and The South-Eastern Norway Regional Health Authority.
Images for cell counting were acquired at the Norbrain Slidescanning
Facility at the Institute of Basic Medical Sciences, University of Oslo,
a resource funded by the Research Council of Norway. The authors
gratefully acknowledge this help as well as help with protein carbonyl
assay from the Regional Core Facility for Mitochondria and Metabolism at
the Oslo University Hospital (http://ous-research.no/mito/).
NR 60
TC 1
Z9 1
U1 8
U2 8
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 DEC
PY 2016
VL 48
BP 34
EP 47
DI 10.1016/j.neurobiolaging.2016.08.005
PG 14
WC Geriatrics & Gerontology; Neurosciences
SC Geriatrics & Gerontology; Neurosciences & Neurology
GA EA9PW
UT WOS:000386977300004
PM 27639119
ER
PT J
AU Lubbe, SJ
Escott-Price, V
Brice, A
Gasser, T
Pittman, AM
Bras, J
Hardy, J
Heutink, P
Wood, NM
Singleton, AB
Grosset, DG
Carroll, CB
Law, MH
Demenais, F
Iles, MM
Bishop, DT
Newton-Bishop, J
Williams, NM
Morris, HR
AF Lubbe, S. J.
Escott-Price, V.
Brice, A.
Gasser, T.
Pittman, A. M.
Bras, J.
Hardy, J.
Heutink, P.
Wood, N. M.
Singleton, A. B.
Grosset, D. G.
Carroll, C. B.
Law, M. H.
Demenais, F.
Iles, M. M.
Bishop, D. T.
Newton-Bishop, J.
Williams, N. M.
Morris, H. R.
CA Melanoma Meta-Anal Consortium
Int Parkinson's Dis Genomics
TI Rare variants analysis of cutaneous malignant melanoma genes in
Parkinson's disease
SO NEUROBIOLOGY OF AGING
LA English
DT Article
DE Parkinson's; Cutaneous malignant melanoma; Shared genetic background;
Pigmentation; Tyrosinase
ID SEQUENCING DATA; SUBSTANTIA-NIGRA; CANCER; RISK; MUTATIONS;
PIGMENTATION; ASSOCIATION; NEUROMELANIN; METAANALYSIS; NEURONS
AB A shared genetic susceptibility between cutaneous malignant melanoma (CMM) and Parkinson's disease (PD) has been suggested. We investigated this by assessing the contribution of rare variants in genes involved in CMM to PD risk. We studied rare variation across 29 CMM risk genes using high-quality genotype data in 6875 PD cases and 6065 controls and sought to replicate findings using whole-exome sequencing data from a second independent cohort totaling 1255 PD cases and 473 controls. No statistically significant enrichment of rare variants across all genes, per gene, or for any individual variant was detected in either cohort. There were nonsignificant trends toward different carrier frequencies between PD cases and controls, under different inheritance models, in the following CMM risk genes: BAP1, DCC, ERBB4, KIT, MAPK2, MITF, PTEN, and TP53. The very rare TYR p.V275F variant, which is a pathogenic allele for recessive albinism, was more common in PD cases than controls in 3 independent cohorts. Tyrosinase, encoded by TYR, is the rate-limiting enzyme for the production of neuromelanin, and has a role in the production of dopamine. These results suggest a possible role for another gene in the dopamine-biosynthetic pathway in susceptibility to neurodegenerative Parkinsonism, but further studies in larger PD cohorts are needed to accurately determine the role of these genes/variants in disease pathogenesis. (C) 2016 The Author(s). Published by Elsevier Inc.
C1 [Lubbe, S. J.; Morris, H. R.] UCL Inst Neurol, Dept Clin Neurosci, London NW3 2PF, England.
[Escott-Price, V.; Williams, N. M.] Cardiff Univ, Sch Med, Inst Psychol Med & Clin Neurosci,Dept Psychol Med, Med Res Council,Ctr Neuropsychiat Genet & Genom, Cardiff, S Glam, Wales.
[Brice, A.] UPMC Univ Paris 06, UMR S 1127, Inst Cerveau & Moelle Epiniere, INSERM,U 1127,CNRS,UMR 7225,Sorbonne Univ,ICM, Paris, France.
[Gasser, T.] Hertie Inst Clin Brain Res, Dept Neurodegenerat Dis, Tubingen, Germany.
[Gasser, T.] German Ctr Neurodegenerat Dis, DZNE, Tubingen, Germany.
[Pittman, A. M.; Bras, J.; Hardy, J.; Wood, N. M.] UCL Inst Neurol, Dept Mol Neurosci, London, England.
[Heutink, P.] Vrije Univ Amsterdam, Med Ctr, Sect Med Genom, Dept Clin Genet, Amsterdam, Netherlands.
[Wood, N. M.] UCL Genet Inst, London, England.
[Singleton, A. B.] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
[Grosset, D. G.] Queen Elizabeth Univ Hosp, Inst Neurol Sci, Dept Neurol, Glasgow, Lanark, Scotland.
[Carroll, C. B.] Univ Plymouth, Peninsula Sch Med, Plymouth, Devon, England.
[Carroll, C. B.] Univ Plymouth, Peninsula Sch Dent, Plymouth, Devon, England.
[Law, M. H.] QIMR Berghofer Med Res Inst, Stat Genet, Brisbane, Qld, Australia.
[Demenais, F.] INSERM, UMR 946, Genet Variat & Human Dis Unit, Paris, France.
[Demenais, F.] Univ Paris Diderot, Inst Univ Hematol, Paris, France.
[Iles, M. M.; Bishop, D. T.; Newton-Bishop, J.] Leeds Inst Canc & Pathol, Sect Epidemiol & Biostat, Leeds, W Yorkshire, England.
RP Morris, HR (reprint author), UCL Inst Neurol, Dept Clin Neurosci, London NW3 2PF, England.
EM h.morris@ucl.ac.uk
RI Hardy, John/C-2451-2009; Morris, Huw/B-8527-2008; Lubbe,
Steven/L-8261-2013; Demenais, Florence/G-3298-2013;
OI Morris, Huw/0000-0002-5473-3774; Demenais, Florence/0000-0001-8361-0936;
Bishop, Tim/0000-0002-8752-8785; Newton Bishop,
Julia/0000-0001-9147-6802
FU Intramural Research Programs of the National Institute of Neurological
Disorders and Stroke (NINDS), the National Institute on Aging (NIA),
National Institutes of Health, Department of Health and Human Services
[Z01-AG000949-02, Z01-ES101986]; National Institute of Environmental
Health Sciences, National Institutes of Health, Department of Health and
Human Services [Z01-AG000949-02, Z01-ES101986]; Department of Defence
[W81XWH-09-2-0128]; Michael J. Fox Foundation for Parkinson's Research;
National Institutes of Health [R01NS037167, R01CA141668, P50NS071674];
American Parkinson Disease Association (APDA); Barnes-Jewish Hospital
Foundation; Greater St Louis Chapter of the APDA; Hersenstichting
Nederland; Neuroscience Campus Amsterdam; section of medical genomics,
the Prinses Beatrix Fonds; Forschungszentrum fur Umwelt und Gesundheit -
German Federal Ministry of Education, Science, Research, and Technology;
State of Bavaria; German National Genome Network (NGFNplus, German
Ministry for Education and Research) [01GS08134]; German Federal
Ministry of Education and Research [NGFN 01GR0468]; ERA-NET NEURON
[01EW0908]; Helmholtz Alliance Mental Health in an Ageing Society -
Initiative and Networking Fund of the Helmholtz Association [HA-215];
French National Agency of Research [ANR-08-MNP-012]; France-Parkinson
Association; French program "Investissements d'avenir" funding
[ANR-10-IAIHU-06]; Assistance Publique - Hopitaux de Paris (PHRC)
[AOR-08010]; Landspitali University Hospital Research Fund; Icelandic
Research Council; European Community [PIAP-GA-2008-230596]; Wellcome
Trust [083948/Z/07/Z, 076113, 085475, 090355]; Medical Research Council
[G0700943, G1100643, G0501542]; Wellcome Trust disease centre
[WT089698/Z/09/Z]; Parkinson's UK [8047, J-0804]; Department of Health's
National Institute for Health Research Biomedical Research Centres
funding; Wellcome Trust/Medical Research Council Joint Call in
Neurodegeneration award [WT089698]; Tracking Parkinson's - Parkinson's
UK - Glasgow University; National Institute for Health Research (NIHR)
DeNDRoN network; NIHR Newcastle Biomedical Research Unit based at
Newcastle upon Tyne Hospitals NHS Foundation Trust and Newcastle
University; NIHRBiomedical Research Centre in Cambridge; Parkinson's UK;
Paul Hamlyn Foundation; Neurosciences Foundation; Dystonia Society;
Michael's Movers; Medical Research Council UK; Ipsen Fund; Motor Neuron
Disease Association; Welsh Assembly Government
FX The authors would like to thank all the subjects who donated their time
and biological samples to be a part of this study. This work was
supported in part by the Intramural Research Programs of the National
Institute of Neurological Disorders and Stroke (NINDS), the National
Institute on Aging (NIA), and the National Institute of Environmental
Health Sciences both part of the National Institutes of Health,
Department of Health and Human Services; project numbers Z01-AG000949-02
and Z01-ES101986. In addition, this work was supported by the Department
of Defence (award W81XWH-09-2-0128), and The Michael J. Fox Foundation
for Parkinson's Research. This work was supported by National Institutes
of Health grants R01NS037167, R01CA141668, P50NS071674, American
Parkinson Disease Association (APDA); Barnes-Jewish Hospital Foundation;
Greater St Louis Chapter of the APDA; Hersenstichting Nederland;
Neuroscience Campus Amsterdam; and the section of medical genomics, the
Prinses Beatrix Fonds. The KORA (Cooperative Research in the Region of
Augsburg) research platform was started and financed by the
Forschungszentrum fur Umwelt und Gesundheit, which is funded by the
German Federal Ministry of Education, Science, Research, and Technology
and by the State of Bavaria. This study was also funded by the German
National Genome Network (NGFNplus number 01GS08134, German Ministry for
Education and Research); by the German Federal Ministry of Education and
Research (NGFN 01GR0468, PopGen); and 01EW0908 in the frame of ERA-NET
NEURON and Helmholtz Alliance Mental Health in an Ageing Society
(HA-215), which was funded by the Initiative and Networking Fund of the
Helmholtz Association. The French GWAS work was supported by the French
National Agency of Research (ANR-08-MNP-012). This study was also funded
by France-Parkinson Association, the French program "Investissements
d'avenir" funding (ANR-10-IAIHU-06) and a grant from Assistance Publique
- Hopitaux de Paris (PHRC, AOR-08010) for the French clinical data. This
study was also sponsored by the Landspitali University Hospital Research
Fund (grant to Sigurlaug Sveinbjornsdottir); Icelandic Research Council
(grant to Sigurlaug Sveinbjornsdottir); and European Community Framework
Programme 7, People Programme, and IAPP on novel genetic and phenotypic
markers of Parkinson's disease and Essential Tremor (MarkMD), contract
number PIAP-GA-2008-230596 MarkMD (to Hjorva Petursson and Johanna
Huttenlocher). This study used the high-performance computational
capabilities of the Biowulf Linux cluster at the National Institutes of
Health, Bethesda, MD, USA (http://biowulf.nih.gov), and DNA panels,
samples, and clinical data from the National Institute of Neurological
Disorders and Stroke Human Genetics Resource Center DNA and Cell Line
Repository. People who contributed samples are acknowledged in
descriptions of every panel on the repository website. The authors thank
the French Parkinson's Disease Genetics Study Group and the Drug
Interaction with genes study group: Y. Agid, M. Anheim, A.-M. Bonnet, M.
Borg, A. Brice, E. Broussolle, J.-C. Corvol, P. Damier, A. Destee, A.
Durr, F. Durif, A. Elbaz, D. Grabil, S. Klebe, P. Krack, E. Lohmann, L.
Lacomblez, M. Martinez, V. Mesnage, P. Pollak, O. Rascol, F. Tison, C.
Tranchant, M. Verin, F. Viallet, and M. Vidailhet. The authors also
thank the members of the French 3C Consortium: A. Alperovitch, C. Berr,
C. Tzourio, and P. Amouyel for allowing us to use part of the 3C cohort,
and D. Zelenika for support in generating the genome-wide molecular
data. The authors thank P.; Tienari (Molecular Neurology Programme,
Biomedicum, University of Helsinki), T. Peuralinna (Department of
Neurology, Helsinki University Central Hospital), L. Myllykangas
(Folkhalsan Institute of Genetics and Department of Pathology,
University of Helsinki), and R. Sulkava (Department of Public Health and
General Practice Division of Geriatrics, University of Eastern Finland)
for the Finnish controls (Vantaa85+ GWAS data). The authors used
genome-wide association data generated by the Wellcome Trust
Case-Control Consortium 2 (WTCCC2) from UK patients with Parkinson's
disease and UK control individuals from the 1958 Birth Cohort and
National Blood Service. Genotyping of UK replication cases on ImmunoChip
was part of the WTCCC2 project, which was funded by the Wellcome Trust
(083948/Z/07/Z). UK population control data was made available through
WTCCC1. This study was supported by the Medical Research Council and
Wellcome Trust disease centre (grant WT089698/Z/09/Z to Nicholas Wood,
John Hardy, and Anthony Schapira). As with previous International
Parkinson's Disease Genomics Consortium efforts, this study makes use of
data generated by the Wellcome Trust Case-Control Consortium. A full
list of the investigators who contributed to the generation of the data
is available from www.wtccc.org.uk. Funding for the project was provided
by the Wellcome Trust under award 076113, 085475, and 090355. This study
was also supported by Parkinson's UK (grants 8047 and J-0804) and the
Medical Research Council (G0700943 and G1100643). The authors thank
Jeffrey Barrett for assistance with the design of the ImmunoChip. DNA
extraction work that was done in the UK was undertaken at University
College London Hospitals, University College London, who received a
proportion of funding from the Department of Health's National Institute
for Health Research Biomedical Research Centres funding. This study was
supported in part by the Wellcome Trust/Medical Research Council Joint
Call in Neurodegeneration award (WT089698) to the Parkinson's disease
Consortium (UKPDC), whose members are from the UCL Institute of
Neurology, University of Sheffield, and the Medical Research Council
Protein Phosphorylation Unit at the University of Dundee. The work was
also supported from the Tracking Parkinson's study, funded by
Parkinson's UK, sponsored by Glasgow University, with support from the
National Institute for Health Research (NIHR) DeNDRoN network, the NIHR
Newcastle Biomedical Research Unit based at Newcastle upon Tyne
Hospitals NHS Foundation Trust and Newcastle University, and the NIHR
funded Biomedical Research Centre in Cambridge. The Molecular Genetic
Studies of Neurodegenerative Disorders was part-funded by Medical
Research Council (G0501542). Steven Lubbe and Huw R Morris made the
conception and design of the study. Steven Lubbe, Valentina
Escott-Price, Nigel M. Williams, and HuwR. Morris performed data
analysis and editing. Jose Bras, Alexis Brice, Thomas Gasser, John
Hardy, Peter Heutink, Nicholas W Wood, Andy B. Singleton, Michael H.
Laws, Donald G. Grosset, Camille B. Carroll, Florence Demenais, Mark M.
Iles, D. Tom Bishop, Julia Newton-Bishop, and Huw R Morris performed
sample and/or data collection. Donald G. Grosset reports grants from
Parkinson's UK, the Paul Hamlyn Foundation, the Neurosciences
Foundation, the Dystonia Society, and Michael's Movers.; Huw R Morris
reports grants from Medical Research Council UK, grants from Wellcome
Trust, grants from Parkinson's UK, grants from Ipsen Fund, during the
conduct of the study; grants from Motor Neuron Disease Association,
grants from Welsh Assembly Government.
NR 55
TC 1
Z9 1
U1 18
U2 18
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 DEC
PY 2016
VL 48
AR 222.e1
DI 10.1016/j.neurobiolaging.2016.07.013
PG 7
WC Geriatrics & Gerontology; Neurosciences
SC Geriatrics & Gerontology; Neurosciences & Neurology
GA EA9PW
UT WOS:000386977300023
PM 27640074
ER
PT J
AU Muterko, A
Kalendar, R
Salina, E
AF Muterko, Alexandr
Kalendar, Ruslan
Salina, Elena
TI Allelic variation at the VERNALIZATION-A1, VRN-B1, VRN-B3, and
PHOTOPERIOD-A1 genes in cultivars of Triticum durum Desf.
SO PLANTA
LA English
DT Article
DE Cereal; Durum wheat; Genetic variation; Photoperiod response;
Vernalization requirement
ID SPRING GROWTH HABIT; MOLECULAR CHARACTERIZATION; TETRAPLOID WHEAT;
PROMOTER REGION; RESPONSE GENES; HEADING TIME; AESTIVUM L.;
IDENTIFICATION; HAPLOTYPES; PPD-A1A
AB The durum wheat varieties from Ukraine, Russia, and Kazakhstan are characterized by the specific allelic composition of the VRN genes that sharply distinguish them from the Triticum durum varieties from other countries. For numerous varieties, the VRN alleles which previously were not found in tetraploid wheat were identified.
The ability of wheat to adapt to a wide range of environmental conditions is mostly determined by the allelic diversity within genes regulating the vernalization requirement (VRN) and photoperiod response (PPD). In the present study, allelic variation in the VRN1, VRN3, and PPD-A1 genes was investigated for 134 varieties of Triticum durum from different eco-geographic areas. It was shown that varieties from Russia and Ukraine have a specific allelic composition at the VRN genes, which in quantity and quality differed from European and American cultivars. A large number of varieties of T. durum from Russia carry the dominant Vrn-A1a.1 allele, previously identified mainly in hexaploid wheat. For some varieties from Eastern Europe and Asia, Vrn-A1i and vrn-A1b.3 recently revealed in wheat were also identified. Polymorphism of the VRN-B1 promoter region, distinguishing all three variants of this sequence (VRN-B1.f, VRN-B1.s, and VRN-B1.m), was detected. It was found that the dominant Vrn-B1c allele is commonly found in varieties of T. durum from Russia and Ukraine, but not Europe or USA. Furthermore, many Ukrainian and Russian varieties carry the dominant alleles of the both VRN-A1 and VRN-B1 genes simultaneously, while varieties from Europe and America carry the dominant allele of VRN-A1 alone. Finally, a high frequency of the Vrn-B3a allele, which previously was found only in some accessions of hexaploid wheat, was observed for varieties from Ukraine and Russia. It was revealed that the Ukrainian pool of T. durum varieties is currently the largest genetic source of the dominant Vrn-B3a allele in wheat in the worldwide.
C1 [Muterko, Alexandr; Salina, Elena] Fed Res Ctr Inst Cytol & Genet, Lavrentyeva Ave 10, Novosibirsk 630090, Russia.
[Muterko, Alexandr] Natl Ctr Seed & Cultivar Invest, Plant Breeding & Genet Inst, Ovidiopolskaya Rd 3, UA-65036 Odessa, Ukraine.
[Kalendar, Ruslan] RSE Natl Ctr Biotechnol, Sh Valikhanov 13-1, Astana 010000, Kazakhstan.
[Kalendar, Ruslan] Univ Helsinki, MTT Plant Genom Lab, Bioctr 3, Viikinkaari 1,POB 65, FIN-00014 Helsinki, Finland.
RP Muterko, A (reprint author), Fed Res Ctr Inst Cytol & Genet, Lavrentyeva Ave 10, Novosibirsk 630090, Russia.; Muterko, A (reprint author), Natl Ctr Seed & Cultivar Invest, Plant Breeding & Genet Inst, Ovidiopolskaya Rd 3, UA-65036 Odessa, Ukraine.
EM muterko@bionet.nsc.ru
RI Kalendar, Ruslan/D-9751-2012;
OI Kalendar, Ruslan/0000-0003-3986-2460; Muterko,
Alexandr/0000-0002-9083-9162
FU Russian Science Foundation [14-14-00161]
FX We are grateful to Carly Schramm for comments and English polishing of
the manuscript. The analysis of 63 T. durum varieties (including all
varieties from Russia) was supported by the Russian Science Foundation
(Project No. 14-14-00161).
NR 25
TC 0
Z9 0
U1 18
U2 18
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0032-0935
EI 1432-2048
J9 PLANTA
JI Planta
PD DEC
PY 2016
VL 244
IS 6
BP 1253
EP 1263
DI 10.1007/s00425-016-2584-5
PG 11
WC Plant Sciences
SC Plant Sciences
GA EA1ME
UT WOS:000386355600007
PM 27522649
ER
PT J
AU Zanotto, C
Bissa, M
Illiano, E
Mezzanotte, V
Marazzi, F
Turolla, A
Antonelli, M
Morghen, CD
Radaelli, A
AF Zanotto, Carlo
Bissa, Massimiliano
Illiano, Elena
Mezzanotte, Valeria
Marazzi, Francesca
Turolla, Andrea
Antonelli, Manuela
Morghen, Carlo De Giuli
Radaelli, Antonia
TI Identification of antibiotic-resistant Escherichia coli isolated from a
municipal wastewater treatment plant
SO CHEMOSPHERE
LA English
DT Article
DE Antibiotic resistance; WWTPs; Escherichia coli; bla and cat genes
ID ANTIMICROBIAL RESISTANCE; BETA-LACTAMASES; HUMAN HEALTH; GENES;
BACTERIA; DISINFECTION; RIVER; WASTEWATERS; ENVIRONMENT; MECHANISMS
AB The emergence and diffusion of antibiotic-resistant bacteria has been a major public health problem for many years now. In this study, antibiotic-resistance of coliforms and Escherichia coli were investigated after their isolation from samples collected in a municipal wastewater treatment plant in the Milan area (Italy) along different points of the treatment sequence: inflow to biological treatment; outflow from biological treatment following rapid sand filtration; and outflow from peracetic acid disinfection. The presence of E. coli that showed resistance to ampicillin (AMP) and chloramphenicol (CAF), used as representative antibiotics for the efficacy against Gram-positive and Gram-negative bacteria, was evaluated. After determining E. coli survival using increasing AMP and CAF concentrations, specific single-resistant (AMPR or CAFR) and double-resistant (AMP(R)/CAF(R)) strains were identified among E. coli colonies, through amplification of the beta-lactamase Tern-1 (bla) and acetyl-transferase catA1 (cat) gene sequences. While a limited number of CAF(R) bacteria was observed, most AMP(R) colonies showed the specific resistance genes to both antibiotics, which was mainly due to the presence of the bla gene sequence. The peracetic acid, used as disinfection agent, showed to be very effective in reducing bacteria at the negligible levels of less than 10 CFU/100 mL, compatible with those admitted for the irrigation use of treated waters. (C) 2016 Published by Elsevier Ltd.
C1 [Zanotto, Carlo] Univ Milan, Dept Med Biotechnol & Translat Med, Via Vanvitelli 32, I-20129 Milan, Italy.
[Bissa, Massimiliano; Illiano, Elena; Radaelli, Antonia] Univ Milan, Dept Pharmacol & Biomol Sci, Via Balzaretti 9, I-20733 Milan, Italy.
[Mezzanotte, Valeria; Marazzi, Francesca] Univ Milano Bicocca, Dept Earth & Environm Sci DISAT, Piazza Sci 1, I-20126 Milan, Italy.
[Turolla, Andrea; Antonelli, Manuela] Politecn Milan, Dept Civil & Environm Engn DICA, Environm Sect, Piazza Leonardo da Vinci 32, I-20133 Milan, Italy.
[Morghen, Carlo De Giuli] Catholic Univ Our Lady Good Counsel, Rr Dritan Hoxha, Tirana, Albania.
[Radaelli, Antonia] Univ Milan, Cellular & Mol Pharmacol Sect, Natl Res Council CNR, Inst Neurosci, Via Vanvitelli 32, I-20129 Milan, Italy.
[Bissa, Massimiliano] NCI, NIH, Basic Res Lab, AMRVS, Bethesda, MD 20892 USA.
RP Radaelli, A (reprint author), Univ Milan, Dept Pharmacol & Biomol Sci, Via Balzaretti 9, I-20733 Milan, Italy.; Morghen, CD (reprint author), Catholic Univ Our Lady Good Counsel, Rr Dritan Hoxha, Tirana, Albania.
EM carlo.zanotto@unimi.it; massimiliano.bissa@nih.gov;
elena.illiano@unimi.it; valeria.mezzanotte@unimib.it;
francesca.marazzi@unimib.it; andrea.turolla@polimi.it;
manuela.antonelli@polimi.it; carlo.degiulimorghen@unimi.it;
antonia.radaelli@unimi.it
OI TUROLLA, ANDREA/0000-0002-2902-5004
FU [18498]; [CUP G42I14001030001]
FX The authors thank Dr. Christopher Berrie for editorial assistance with
the manuscript. This work was partially founded by the Transition Grant,
code no. 18498, CUP G42I14001030001.
NR 43
TC 1
Z9 1
U1 92
U2 92
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0045-6535
EI 1879-1298
J9 CHEMOSPHERE
JI Chemosphere
PD DEC
PY 2016
VL 164
BP 627
EP 633
DI 10.1016/j.chemosphere.2016.08.040
PG 7
WC Environmental Sciences
SC Environmental Sciences & Ecology
GA DY7OG
UT WOS:000385318200073
PM 27635645
ER
PT J
AU Hagen, EM
Sicko, RJ
Kay, DM
Rigler, SL
Dimopoulos, A
Ahmad, S
Doleman, MH
Fan, RZ
Romitti, PA
Browne, ML
Caggana, M
Brody, LC
Shaw, GM
Jelliffe-Pawlowski, LL
Mills, JL
AF Hagen, Erin M.
Sicko, Robert J.
Kay, Denise M.
Rigler, Shannon L.
Dimopoulos, Aggeliki
Ahmad, Shabbir
Doleman, Margaret H.
Fan, Ruzong
Romitti, Paul A.
Browne, Marilyn L.
Caggana, Michele
Brody, Lawrence C.
Shaw, Gary M.
Jelliffe-Pawlowski, Laura L.
Mills, James L.
TI Copy-number variant analysis of classic heterotaxy highlights the
importance of body patterning pathways
SO HUMAN GENETICS
LA English
DT Article
ID CONGENITAL HEART-DISEASE; PRIMARY CILIARY DYSKINESIA; LEFT-RIGHT
ASYMMETRY; MOUSE EMBRYOS; DEFECTS; ZEBRAFISH; PREVALENCE; GENETICS;
GENES
AB Classic heterotaxy consists of congenital heart defects with abnormally positioned thoracic and abdominal organs. We aimed to uncover novel, genomic copy-number variants (CNVs) in classic heterotaxy cases. A microarray containing 2.5 million single-nucleotide polymorphisms (SNPs) was used to genotype 69 infants (cases) with classic heterotaxy identified from California live births from 1998 to 2009. CNVs were identified using the PennCNV software. We identified 56 rare CNVs encompassing genes in the NODAL (NIPBL, TBX6), BMP (PPP4C), and WNT (FZD3) signaling pathways, not previously linked to classic heterotaxy. We also identified a CNV involving FGF12, a gene previously noted in a classic heterotaxy case. CNVs involving RBFOX1 and near MIR302F were detected in multiple cases. Our findings illustrate the importance of body patterning pathways for cardiac development and left/right axes determination. FGF12, RBFOX1, and MIR302F could be important in human heterotaxy, because they were noted in multiple cases. Further investigation into genes involved in the NODAL, BMP, and WNT body patterning pathways and into the dosage effects of FGF12, RBFOX1, and MIR302F is warranted.
C1 [Hagen, Erin M.; Rigler, Shannon L.; Dimopoulos, Aggeliki; Fan, Ruzong; Mills, James L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Intramural Populat Hlth Res, NIH, 6100 Execut Blvd, Bethesda, MD 20892 USA.
[Sicko, Robert J.; Kay, Denise M.; Caggana, Michele] New York State Dept Hlth, Wadsworth Ctr, 120 New Scotland Ave, Albany, NY 12201 USA.
[Ahmad, Shabbir; Doleman, Margaret H.] Calif Dept Publ Hlth, Calif Birth Defects Monitoring Program, 1615 Capitol Ave,MS 8304, Sacramento, CA 95899 USA.
[Romitti, Paul A.] Univ Iowa, Coll Publ Hlth, Dept Epidemiol, 145 N Riverside Dr,S416 CPHB, Iowa City, IA 52242 USA.
[Browne, Marilyn L.] New York State Dept Hlth, Congenital Malformat Registry, Empire State Plaza Corning Tower, Albany, NY 12237 USA.
[Browne, Marilyn L.] SUNY Albany, Sch Publ Hlth, 1400 Washington Ave, Albany, NY 12222 USA.
[Brody, Lawrence C.] NHGRI, Genome Technol Branch, NIH, Bldg 50,50 South Dr,MSC 8004, Bethesda, MD 20892 USA.
[Shaw, Gary M.] Stanford Univ, Sch Med, Dept Pediat, Med Off Bldg,1265 Welch Rd Room X159, Stanford, CA 94305 USA.
[Jelliffe-Pawlowski, Laura L.] Univ Calif San Francisco, Sch Med, Dept Epidemiol & Biostat, 550 16th St, San Francisco, CA 94158 USA.
RP Mills, JL (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Intramural Populat Hlth Res, NIH, 6100 Execut Blvd, Bethesda, MD 20892 USA.
EM jamesmills@nih.gov
FU Intramural Research Program of the National Institutes of Health, Eunice
Kennedy Shriver National Institute of Child Health and Human Development
[HHSN275201100001I, HHSN27500005, N01-DK-73431]; CDC [5U01DD001033]; NIH
[R01HL092330]
FX This work was funded by the Intramural Research Program of the National
Institutes of Health, Eunice Kennedy Shriver National Institute of Child
Health and Human Development (Contracts HHSN275201100001I, HHSN27500005,
and N01-DK-73431). Dr. Shaw was partially supported for this work by
funds from CDC (5U01DD001033) and NIH (R01HL092330).
NR 39
TC 0
Z9 0
U1 8
U2 8
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0340-6717
EI 1432-1203
J9 HUM GENET
JI Hum. Genet.
PD DEC
PY 2016
VL 135
IS 12
BP 1355
EP 1364
DI 10.1007/s00439-016-1727-x
PG 10
WC Genetics & Heredity
SC Genetics & Heredity
GA DY7YT
UT WOS:000385345900004
PM 27637763
ER
PT J
AU Darvishi, E
Woldemichael, GM
AF Darvishi, Emad
Woldemichael, Girma M.
TI Cycloheximide Inhibits Actin Cytoskeletal Dynamics by Suppressing
Signaling via RhoA
SO JOURNAL OF CELLULAR BIOCHEMISTRY
LA English
DT Article
DE CYCLOHEXIMIDE; YEAST KNOCKOUT COLLECTION; ACTIN CYTOSKELETON;
MICROFILAMENTS; SMALL GTPase RhoA
ID EPIDERMAL-GROWTH-FACTOR; TRANSLATION ELONGATION; YEAST ACTIN;
G-PROTEINS; IN-VIVO; GENE; ENDOCYTOSIS; INTEGRITY; INSULIN; COMPLEX
AB Genome-wide screening of the yeast Saccharomyces cerevisiae knockout collection was used to characterize chemical-genetic interactions of cycloheximide (CHX). The results showed that while the act1 mutant was the only deletion mutant in the heterozygous essential gene deletion collection that showed hypersensitivity to sub-inhibitory concentrations of CHX, deletion of nonessential genes that work in concert with either cytoplasmic or nuclear actin in the homozygous deletion collection also highly sensitized yeast to CHX. Fluorescence microscopy analysis revealed that CHX disrupts filamentous actin structures and fluid phase endocytosis in the yeast cell. It also showed that CHX disrupts transforming growth factor-1 (TGF-1)-induced actin reorganization and polygonal architecture of microfilaments in mammalian cells. This inhibitory effect is mediated, at least in part, through the actin dynamics signaling pathway via suppression of activation of the small GTPase RhoA. J. Cell. Biochem. 117: 2886-2898, 2016. (c) 2016 Wiley Periodicals, Inc.
C1 [Darvishi, Emad] NCI, Mol Targets Lab, NIH, Frederick Natl Lab, Frederick, MD 21702 USA.
[Woldemichael, Girma M.] Leidos Biomedical Res Inc, Basic Sci Program, Mol Targets Lab, Frederick Natl Lab, Frederick, MD 21702 USA.
RP Woldemichael, GM (reprint author), Frederick Natl Lab, Mol Targets Lab, Bldg 538,Rm 131,1050 Boyles St, Frederick, MD 21702 USA.
EM woldemichaelg@mail.nih.gov
FU Frederick National Laboratory for Cancer Research, National Institutes
of Health [HHSN261200800001E]
FX Grant sponsor: Frederick National Laboratory for Cancer Research,
National Institutes of Health; Grant number: HHSN261200800001E.
NR 43
TC 0
Z9 0
U1 6
U2 6
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0730-2312
EI 1097-4644
J9 J CELL BIOCHEM
JI J. Cell. Biochem.
PD DEC
PY 2016
VL 117
IS 12
BP 2886
EP 2898
DI 10.1002/jcb.25601
PG 13
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA DZ4MI
UT WOS:000385832400021
PM 27192630
ER
PT J
AU Saproo, S
Shih, V
Jangraw, DC
Sajda, P
AF Saproo, Sameer
Shih, Victor
Jangraw, David C.
Sajda, Paul
TI Neural mechanisms underlying catastrophic failure in human-machine
interaction during aerial navigation
SO JOURNAL OF NEURAL ENGINEERING
LA English
DT Article
DE motor control; flight; EEG; boundary avoidance task; pilot induced
oscillations; pupillometry; rapid decision making
ID ANTERIOR CINGULATE CORTEX; LOCUS-COERULEUS; MENTAL WORKLOAD; EEG; EMG
AB Objective. We investigated the neural correlates of workload buildup in a fine visuomotor task called the boundary avoidance task (BAT). The BAT has been known to induce naturally occurring failures of human-machine coupling in high performance aircraft that can potentially lead to a crash-these failures are termed pilot induced oscillations (PIOs). Approach. We recorded EEG and pupillometry data from human subjects engaged in a flight BAT simulated within a virtual 3D environment. Main results. We find that workload buildup in a BAT can be successfully decoded from oscillatory features in the electroencephalogram (EEG). Information in delta, theta, alpha, beta, and gamma spectral bands of the EEG all contribute to successful decoding, however gamma band activity with a lateralized somatosensory topography has the highest contribution, while theta band activity with a fronto-central topography has the most robust contribution in terms of real-world usability. We show that the output of the spectral decoder can be used to predict PIO susceptibility. We also find that workload buildup in the task induces pupil dilation, the magnitude of which is significantly correlated with the magnitude of the decoded EEG signals. These results suggest that PIOs may result from the dysregulation of cortical networks such as the locus coeruleus (LC)-anterior cingulate cortex (ACC) circuit. Significance. Our findings may generalize to similar control failures in other cases of tight man-machine coupling where gains and latencies in the control system must be inferred and compensated for by the human operators. A closed-loop intervention using neurophysiological decoding of workload buildup that targets the LC-ACC circuit may positively impact operator performance in such situations.
C1 [Saproo, Sameer; Shih, Victor; Sajda, Paul] Columbia Univ, Dept Biomed Engn, New York, NY 10027 USA.
[Jangraw, David C.] NIH, Bldg 10, Bethesda, MD 20892 USA.
RP Saproo, S; Sajda, P (reprint author), Columbia Univ, Dept Biomed Engn, New York, NY 10027 USA.
EM sameer.saproo@columbia.edu; psajda@columbia.edu
OI Sajda, Paul/0000-0002-9738-1342
FU Defense Advanced Research Projects Agency (DARPA); Army Research Office
(ARO) [W911NF-11-1-0219]; Army Research Laboratory [W911NF-10-2-0022];
UK Economic and Social Research Council [ES/L012995/1]
FX The authors would like to thank Eric Pohlmeyer and Mark Chevillet for
their helpful comments and suggestions, and acknowledge Sona Roy and
Wha-Yin Hsu for their assistance with data collection. The work was
funded by the Defense Advanced Research Projects Agency (DARPA) and Army
Research Office (ARO) under grant number W911NF-11-1-0219, the Army
Research Laboratory under Cooperative agreement number W911NF-10-2-0022
and the UK Economic and Social Research Council under grant number
ES/L012995/1. The views and conclusions contained in this document are
those of the authors and should not be interpreted as representing the
official policies, either expressed or implied, of the US Government.
The US Government is authorized to reproduce and distribute reprints for
Government purposes notwithstanding any copyright notation herein.
NR 27
TC 0
Z9 0
U1 7
U2 7
PU IOP PUBLISHING LTD
PI BRISTOL
PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND
SN 1741-2560
EI 1741-2552
J9 J NEURAL ENG
JI J. Neural Eng.
PD DEC
PY 2016
VL 13
IS 6
AR 066005
DI 10.1088/1741-2560/13/6/066005
PG 11
WC Engineering, Biomedical; Neurosciences
SC Engineering; Neurosciences & Neurology
GA DZ5XE
UT WOS:000385934600005
PM 27705959
ER
PT J
AU Biggs, ML
Doody, DR
Trabert, B
Starr, JR
Chen, C
Schwartz, SM
AF Biggs, Mary L.
Doody, David R.
Trabert, Britton
Starr, Jacqueline R.
Chen, Chu
Schwartz, Stephen M.
TI Consumption of alcoholic beverages in adolescence and adulthood and risk
of testicular germ cell tumor
SO INTERNATIONAL JOURNAL OF CANCER
LA English
DT Article
DE alcohol drinking; epidemiology; nonseminoma; seminoma; testicular germ
cell tumor
ID MARIJUANA USE; TESTIS CANCER; TRENDS; POPULATION; COHORT; ASSOCIATION;
MORTALITY; HORMONES; SEX; AGE
AB The etiology of testicular germ cell tumor (TGCT) remains obscure and accumulating evidence suggests that postnatal environmental or lifestyle factors may play a role. To investigate whether consumption of alcoholic beverages during adolescence or adulthood is associated with TGCT risk, we analyzed data from a USA population-based case-control study of 540 18-44 year-old TGCT cases and 1,280 age-matched controls. Participants were queried separately about consumption of beer, wine and liquor during grades 7-8, grades 9-12 and the 5 years before reference date (date of diagnosis for cases and corresponding date for controls). We used logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI) for the association of TGCT risk with alcoholic beverage consumption during the different periods, both total and by specific beverage types and separately for seminomas and nonseminomas. Compared with nondrinkers in the 5 years before reference date, the OR (95% CI) for 1-6, 7-13 and 14 drinks per week were 1.20 (0.85, 1.69), 1.23 (0.81, 1.85) and 1.56 (1.03, 2.37), respectively (p-trend=0.04). The corresponding results for alcohol consumption in grades 9-12 were 1.39 (1.06, 1.82), 1.07 (0.72, 1.60), 1.53 (1.01, 2.31) (p-trend=0.05). Alcohol consumption in grades 7-8 was uncommon and no statistically significant associations with TGCT were observed. Associations with alcohol consumption in the 5 years before reference date appeared stronger for nonseminomas than for seminomas, but the differences were not statistically significant (p0.10). Associations were similar across different alcoholic beverage types. Consumption of alcoholic beverages may be associated with an increased TGCT risk.
What's new? Drinking alcohol appears to boost risk of testicular cancer, according to new analysis. Not much is known about the causes of TGCT and these authors wondered if alcohol consumption might play a role. They interviewed 540 cases and 1280 controls about their consumption of beer, wine and liquor during high school and in the 5 years prior to diagnosis (or a randomly assigned reference date, for controls). Those who imbibed two or more drinks per day, in either time period, increased their risk by 50% compared with nondrinkers.
C1 [Biggs, Mary L.] Univ Washington, Sch Publ Hlth, Dept Biostat, Seattle, WA 98195 USA.
[Doody, David R.; Chen, Chu; Schwartz, Stephen M.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, POB 19024, Seattle, WA 98109 USA.
[Trabert, Britton] NCI, Div Canc Epidemiol & Genet, Rockville, MD USA.
[Starr, Jacqueline R.; Chen, Chu; Schwartz, Stephen M.] Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA.
[Starr, Jacqueline R.] Forsyth Inst, Dept Appl Oral Sci, Cambridge, MA USA.
[Starr, Jacqueline R.] Harvard Sch Dent Med, Dept Oral Hlth Policy & Epidemiol, Boston, MA USA.
RP Schwartz, SM (reprint author), Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, POB 19024, Seattle, WA 98109 USA.
EM sschwart@fhcrc.org
RI Trabert, Britton/F-8051-2015
FU U.S. National Cancer Institute [R01CA085914, N01PC067009, N01PC35142,
T32ES007262]
FX Grant sponsor: U.S. National Cancer Institute; Grant numbers:
R01CA085914; N01PC067009; N01PC35142; T32ES007262
NR 32
TC 0
Z9 0
U1 33
U2 33
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0020-7136
EI 1097-0215
J9 INT J CANCER
JI Int. J. Cancer
PD DEC 1
PY 2016
VL 139
IS 11
BP 2405
EP 2414
DI 10.1002/ijc.30368
PG 10
WC Oncology
SC Oncology
GA DX8NQ
UT WOS:000384646200003
PM 27474852
ER
PT J
AU Liu, ZW
Coghill, AE
Pfeiffer, RM
Hsu, WL
Lou, PJ
Wang, CP
Yu, KJ
Niwa, S
Brotzman, M
Ye, WM
Chen, CJ
Hildesheim, A
AF Liu, Zhiwei
Coghill, Anna E.
Pfeiffer, Ruth M.
Hsu, Wan-Lun
Lou, Pei-Jen
Wang, Cheng-Ping
Yu, Kelly J.
Niwa, Shelley
Brotzman, Michelle
Ye, Weimin
Chen, Chien-Jen
Hildesheim, Allan
TI Birth order and risk of nasopharyngeal carcinoma in multiplex families
from Taiwan
SO INTERNATIONAL JOURNAL OF CANCER
LA English
DT Article
DE birth order; Epstein-Barr virus; multiplex family; infant-contact;
nasopharyngeal carcinoma; Taiwan
ID EPSTEIN-BARR-VIRUS; CD8(+) T-CELLS; INFECTIOUS-MONONUCLEOSIS; HODGKINS
LYMPHOMA; EARLY-LIFE; POPULATION; DISEASES; CYTOMEGALOVIRUS;
INDIVIDUALS; CHILDHOOD
AB A small proportion of individuals infected with Epstein-Barr virus (EBV) develop nasopharyngeal carcinoma (NPC). Timing of initial exposure could alter immunological responses to primary EBV infection and explain variation in cancer risk later in life. We measured early life family structure as a proxy for the timing of primary EBV infection to examine whether earlier age at infection alters NPC risk. We utilized data from 480 NPC cases and 1,291 unaffected siblings from Taiwanese NPC multiplex families ( 2 family members with NPC, N=2,921). Information on birth order within the family was derived from questionnaires. We utilized logistic regression models to examine the association between birth order and NPC, accounting for correlations between relatives. Within these high-risk families, older siblings had an elevated risk of NPC. Compared with being a first-born child, the risk (95% CIs) of NPC associated with a birth order of two, three, four and five or more was 1.00 (0.71, 1.40), 0.88 (0.62, 1.24), 0.74 (0.53, 1.05) and 0.60 (0.43, 0.82), respectively (P for trend=0.002). We observed no associations between NPC risk and the number of younger siblings or cumulative infant-years exposure. These associations were not modified by underlying genetic predisposition or family size. We observed that early life family structure was important for NPC risk in NPC multiplex families, with older siblings having a greater risk of disease. Future studies focusing on more direct measures of the immune response to EBV in early childhood could elucidate the underlying mechanisms.
What's new? Got cancer? Blame your baby siblings. New analysis suggests that being an older sibling increase your likelihood of developing nasopharyngeal cancer (NPC) in high-risk populations. Infection with the Epstein-Barr virus can lead to cancer later in life, but whether age at primary infection alters the risk of NPC in endemic areas is unknown. Using the presence of siblings as a proxy for early childhood exposure to the virus, these authors collected birth order information from NPC cases and controls in NPC multiplex families in Taiwan. They found that older siblings did have a higher incidence of NPC than subsequent children, suggesting that timing at EBV infection may pave the way for NPC later in life.
C1 [Liu, Zhiwei; Ye, Weimin] Karolinska Inst, Dept Med Epidemiol & Biostat, S-17177 Stockholm, Sweden.
[Coghill, Anna E.; Pfeiffer, Ruth M.; Yu, Kelly J.; Hildesheim, Allan] NCI, Div Canc Epidemiol & Genet, 9609 Med Ctr Dr, Rockville, MD USA.
[Hsu, Wan-Lun; Chen, Chien-Jen] Acad Sinica, Genom Res Ctr, Taipei, Taiwan.
[Lou, Pei-Jen; Wang, Cheng-Ping] Natl Taiwan Univ Hosp, Dept Otolaryngol, Taipei, Taiwan.
[Lou, Pei-Jen; Wang, Cheng-Ping] Natl Taiwan Univ, Coll Med, Taipei, Taiwan.
[Niwa, Shelley; Brotzman, Michelle] Westat Corp, 1600 Res Blvd, Rockville, MD USA.
[Chen, Chien-Jen] Natl Taiwan Univ, Coll Publ Hlth, Grad Inst Epidemiol & Prevent Med, Taipei, Taiwan.
RP Liu, ZW (reprint author), Karolinska Inst, Dept Med Epidemiol & Biostat, S-17177 Stockholm, Sweden.
EM zhiwei.liu@ki.se
FU Intramural Research Program of the National Cancer Institute at the
National Institutes of Health; Karolinska Institutet (KID)
FX Grant sponsors: Intramural Research Program of the National Cancer
Institute at the National Institutes of Health and Karolinska Institutet
(KID; to Z.L.)
NR 30
TC 0
Z9 0
U1 10
U2 10
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0020-7136
EI 1097-0215
J9 INT J CANCER
JI Int. J. Cancer
PD DEC 1
PY 2016
VL 139
IS 11
BP 2467
EP 2473
DI 10.1002/ijc.30390
PG 7
WC Oncology
SC Oncology
GA DX8NQ
UT WOS:000384646200009
PM 27537611
ER
PT J
AU Mascia, F
Schloemann, DT
Cataisson, C
McKinnon, KM
Krymskaya, L
Wolcott, KM
Yuspa, SH
AF Mascia, Francesca
Schloemann, Derek T.
Cataisson, Christophe
McKinnon, Katherine M.
Krymskaya, Ludmila
Wolcott, Karen M.
Yuspa, Stuart H.
TI Cell autonomous or systemic EGFR blockade alters the immune-environment
in squamous cell carcinomas
SO INTERNATIONAL JOURNAL OF CANCER
LA English
DT Article
DE EGFR; SCC; gefitinib; tumor immune-environment; T regulatory cells
ID GROWTH-FACTOR RECEPTOR; CANCER; CARCINOGENESIS; KERATINOCYTES;
INHIBITORS; MICE
AB Targeting mutations and amplifications in the EGFR has been successful precision therapy for cancers of the lung, oral cavity and gastrointestinal track. However, a systemic immune reaction manifested by dose-limiting inflammation in the skin and gut has been a consistent adverse effect. To address the possibility that intra-tumoral immune changes contribute to the anti-cancer activity of EGFR inhibition, squamous cancers were produced by syngeneic orthografts of either EGFR null or wildtype mouse primary keratinocytes transduced with an oncogenic H-ras retrovirus. Flow cytometric, RNA and Bioplex immunoassay analyses of the tumor immune milieu were performed. Cancers forming from keratinocytes genetically depleted of EGFR were smaller than wildtype cancers and had fewer infiltrating FoxP3 Treg cells, lower Foxp3 RNA and a lower percentage of CD4 PD1 positive cells indicating a tumor cell autonomous regulation of its microenvironment. Hosts bearing wildtype cancers treated with gefitinib for 1 week showed a trend for smaller tumors. In this short term pharmacological model, there was also a trend to reduced FoxP3 cells and FoxP3 RNA in the tumors of treated mice as well as a substantial increase in the ratio of IL-1A/IL-1RA transcripts. These results suggest that relatively brief systemic inhibition of EGFR signaling alters the immune environment of the targeted cancer. Together these data imply that an EGFR dependent Treg function supports the growth of squamous cancers and is a target for the therapeutic activity of EGFR inhibition.
What's new? Precision therapy targeting the epidermal growth factor receptor (EGFR) is effective in lung, oral cavity, and gastrointestinal cancer. However, a systemic immune reaction resulting in dose-limiting inflammation in the skin and gut has been a consistent adverse effect. To determine whether immune effectors could contribute to the anti-cancer response, here the authors produced in mice squamous cancers that were either genetically deleted of EGFR or subjected to systemic treatment with gefitinib. Tumor cell autonomous (genetic) or systemic (pharmacologic) inhibition of EGFR signaling reduced tumor growth and Treg infiltration in the microenvironment, suggesting that EGFR-targeted cancer therapy may indeed involve immunomodulation.
C1 [Mascia, Francesca; Schloemann, Derek T.; Cataisson, Christophe; Yuspa, Stuart H.] NCI, Lab Canc Biol & Genet, NIH, Bethesda, MD 20892 USA.
[Mascia, Francesca] US FDA, Lab Appl Biochem, Div Biotechnol Res & Review 3, Off Biotechnol Prod,Off Pharmaceut Qual,Ctr Drug, Silver Spring, MD USA.
[McKinnon, Katherine M.] NCI, FACS Core Facil, Vaccine Branch, NIH, Bethesda, MD 20892 USA.
[Krymskaya, Ludmila; Wolcott, Karen M.] NCI, FACS Core Facil, Lab Genome Integr, NIH, Bethesda, MD 20892 USA.
RP Yuspa, SH (reprint author), NCI, Lab Canc Biol & Genet, CCR NIH, 37 Convent Dr,Bldg 37 Rm 4068, Bethesda, MD 20892 USA.
EM Yuspas@dc37a.Nci.Nih.Gov
FU Intramural Research Program of the NIH, NCI, Center for Cancer Research
[BC005445-30]
FX Grant sponsor: Intramural Research Program of the NIH, NCI, Center for
Cancer Research, Project BC005445-30.
NR 15
TC 0
Z9 0
U1 31
U2 31
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0020-7136
EI 1097-0215
J9 INT J CANCER
JI Int. J. Cancer
PD DEC 1
PY 2016
VL 139
IS 11
BP 2593
EP 2597
DI 10.1002/ijc.30376
PG 5
WC Oncology
SC Oncology
GA DX8NQ
UT WOS:000384646200021
PM 27509256
ER
PT J
AU Schiffman, M
Hyun, N
Raine-Bennett, TR
Katki, H
Fetterman, B
Gage, JC
Cheung, LC
Befano, B
Poitras, N
Lorey, T
Castle, PE
Wentzensen, N
AF Schiffman, Mark
Hyun, Noorie
Raine-Bennett, Tina R.
Katki, Hormuzd
Fetterman, Barbara
Gage, Julia C.
Cheung, Li C.
Befano, Brian
Poitras, Nancy
Lorey, Thomas
Castle, Philip E.
Wentzensen, Nicolas
TI A cohort study of cervical screening using partial HPV typing and
cytology triage
SO INTERNATIONAL JOURNAL OF CANCER
LA English
DT Article
DE cervix; HPV; screening; cancer; cytology
ID CARCINOGENIC HUMAN-PAPILLOMAVIRUS; 5-YEAR RISKS; CANCER RISK; WOMEN;
MANAGEMENT; GUIDELINES; SPECIMENS; PERFORMANCE; PREVENTION; PRECANCER
AB HPV testing is more sensitive than cytology for cervical screening. However, to incorporate HPV tests into screening, risk-stratification (triage) of HPV-positive women is needed to avoid excessive colposcopy and overtreatment. We prospectively evaluated combinations of partial HPV typing (Onclarity, BD) and cytology triage, and explored whether management could be simplified, based on grouping combinations yielding similar 3-year or 18-month CIN3+ risks. We typed approximate to 9,000 archived specimens, taken at enrollment (2007-2011) into the NCI-Kaiser Permanente Northern California (KPNC) HPV Persistence and Progression (PaP) cohort. Stratified sampling, with reweighting in the statistical analysis, permitted risk estimation of HPV/cytology combinations for the 700,000+-woman KPNC screening population. Based on 3-year CIN3+ risks, Onclarity results could be combined into five groups (HPV16, else HPV18/45, else HPV31/33/58/52, else HPV51/35/39/68/56/66/68, else HPV negative); cytology results fell into three risk groups (high-grade, ASC-US/LSIL, NILM). For the resultant 15 HPV group-cytology combinations, 3-year CIN3+ risks ranged 1,000-fold from 60.6% to 0.06%. To guide management, we compared the risks to established benchmark risk/management thresholds in this same population (e.g., LSIL predicted 3-year CIN3+ risk of 5.8% in the screening population, providing the benchmark for colposcopic referral). By benchmarking to 3-year risk thresholds (supplemented by 18-month estimates), the widely varying risk strata could be condensed into four action bands (very high risk of CIN3+ mandating consideration of cone biopsy if colposcopy did not find precancer; moderate risk justifying colposcopy; low risk managed by intensified follow-up to permit HPV clearance; and very low risk permitting routine screening.) Overall, the results support primary HPV testing, with management of HPV-positive women using partial HPV typing and cytology.
What's new? Cervical cancer screening includes two elements: cytology and HPV testing. But many women who test positive for HPV won't need further examination; most HPV infections don't lead to cancer. How best to identify those at risk? These authors created a system to simplify risk assessment. By conducting a cohort study to document the likelihood of patients developing CIN3 within three years, they evaluated different patterns of screening results. They were able to stratify risk profiles generated by HPV typing and cytology into four action bands, or further screening recommendations, thus balancing the sensitivity of HPV typing with simplicity of implementation.
C1 [Schiffman, Mark; Hyun, Noorie; Katki, Hormuzd; Gage, Julia C.; Wentzensen, Nicolas] NCI, Div Canc Epidemiol & Genet, Rockville, MD USA.
[Raine-Bennett, Tina R.] Kaiser Permanente Northern Calif, Div Res, Oakland, CA USA.
[Fetterman, Barbara; Poitras, Nancy; Lorey, Thomas] Kaiser Permanente Northern Calif, Reg Lab, Berkeley, CA USA.
[Cheung, Li C.; Befano, Brian] Informat Management Serv Inc, Calverton, MD USA.
[Castle, Philip E.] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA.
RP Schiffman, M (reprint author), Room 6E544,9609 Med Ctr Dr, Rockville, MD 20850 USA.
EM schiffmm@exchange.nih.gov
OI Cheung, Li/0000-0003-1625-4331
FU Gen-Probe/Hologic; Roche; Cepheid; ClearPath; Guided Therapeutics; Teva
Pharmaceutics; Genticel; Inovio; GE Healthcare
FX Drs. Schiffman and Gage report that NCI has received testing of
specimens from the PaP cohort at reduced or no cost, for NCI-led studies
from Roche and BD. Dr. Wentzensen reports receiving testing of specimens
at reduced or no cost for NCI-led studies from Roche, BD, and Hologic.
Dr. Castle has received commercial HPV tests for research at a reduced
or no cost from Roche, Qiagen, Norchip, Arbor Vita Corporation, BD and
mtm. He has been compensated financially as a member of a Merck Data and
Safety Monitoring Board for HPV vaccines. Dr. Castle has been paid as
consultant for Gen-Probe/Hologic, Roche, Cepheid, ClearPath, Guided
Therapeutics, Teva Pharmaceutics, Genticel, Inovio and GE Healthcare.
Dr. Castle has received honoraria as a speaker for Roche and Cepheid.
NR 38
TC 1
Z9 1
U1 8
U2 8
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0020-7136
EI 1097-0215
J9 INT J CANCER
JI Int. J. Cancer
PD DEC 1
PY 2016
VL 139
IS 11
BP 2606
EP 2615
DI 10.1002/ijc.30375
PG 10
WC Oncology
SC Oncology
GA DX8NQ
UT WOS:000384646200023
PM 27509172
ER
PT J
AU Akhtar, R
Graham, HK
Derby, B
Sherratt, MJ
Trafford, AW
Chadwick, RS
Gavara, N
AF Akhtar, R.
Graham, H. K.
Derby, B.
Sherratt, M. J.
Trafford, A. W.
Chadwick, R. S.
Gavara, N.
TI Frequency-modulated atomic force microscopy localises viscoelastic
remodelling in the ageing sheep aorta
SO JOURNAL OF THE MECHANICAL BEHAVIOR OF BIOMEDICAL MATERIALS
LA English
DT Article
DE Frequency-modulated atomic force; microscopy; Aorta; Ageing; Lamellar;
Medial layer
ID ELASTIC PROPERTIES; LAMELLAR UNIT; SOFT-TISSUES; NANOINDENTATION;
INDENTATION; ARTERIES
AB Age-related aortic stiffening is associated with cardiovascular diseases such as heart failure. The mechanical functions of the main structural components of the aorta, such as collagen and elastin, are determined in part by their organisation at the micrometer length scale. With age and disease both components undergo aberrant remodelling, hence, there is a need for accurate characterisation of the biomechanical properties at this length scale. In this study we used a frequency-modulated atomic force microscopy (FM-AFM) technique on a model of ageing in female sheep aorta (young: 18 months, old: >8 years) to measure the micromechanical properties of the medial layer of the ascending aorta. The novelty of our FM-AFM method, operated at 30 kHz, is that it is non-contact and can be performed on a conventional AFM using the 'cantilever tune' mode, with a spatial (areal) resolution of around 1.6 mu m(2). We found significant changes in the elastic and viscoelastic properties within the medial lamellar unit (elastic lamellae and adjacent inter-lamellar space) with age. In particular, there was an increase in elastic modulus (Young; geometric mean (geometric SD)=42.9 (2.26) kPa, Old=113.9 (2.57) kPa, P < 0.0001), G' and G" (storage and loss modulus respectively) (Young; G' = 14.3 (2.26) kPa, Old G' = 38.0 (2.57) kPa, P < 0.0001; Young; G"=14.5 (2.56) kPa, Old G"=32.8 (2.52) kPa, P<0.0001). The trends observed in the elastic properties with FM-AFM matched those we have previously found using scanning acoustic microscopy (SAM). The utility of the FM-AFM method is that it does not require custom AFM hardware and can be used to simultaneously determine the elastic and viscoelastic behaviour of a biological sample.
C1 [Akhtar, R.] Univ Liverpool, Sch Engn, Ctr Mat & Struct, Liverpool L69 3GH, Merseyside, England.
[Graham, H. K.; Sherratt, M. J.] Univ Manchester, Manchester Acad & Hlth Sci Ctr, Inst Inflammat & Repair, Stopford Bldg, Manchester M13 9PT, Lancs, England.
[Derby, B.] Univ Manchester, Sch Mat, Oxford Rd, Manchester M13 9PL, Lancs, England.
[Trafford, A. W.] Univ Manchester, Fac Med & Human Sci, Inst Cardiovasc Sci, 46 Grafton St, Manchester M13 9NT, Lancs, England.
[Chadwick, R. S.] Natl Inst Deafness & Other Commun Disorders, Auditory Mech Sect, NIH, Bethesda, MD USA.
[Gavara, N.] Queen Mary Univ London, Sch Engn & Mat Sci, Mile End Rd, London E1 4NS, England.
RP Akhtar, R (reprint author), Univ Liverpool, Sch Engn, Ctr Mat & Struct, Liverpool L69 3GH, Merseyside, England.
EM r.akhtar@liverpool.ac.uk
RI Derby, Brian/E-3529-2010
OI Derby, Brian/0000-0001-5753-0166
FU Royal Society [R112205]; Wellcome Trust Value in People Award; Medical
Research Council [G1001398]
FX We gratefully acknowledge funding from the Royal Society for the
provision of an International Travel Grant for Collaboration (R112205)
to RA, and Wellcome Trust Value in People Award to RA and MJS. MJS and
BD gratefully acknowledge the support of the Medical Research Council
(www.mrc.ac.uk: grant reference G1001398).
NR 28
TC 0
Z9 0
U1 27
U2 27
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1751-6161
EI 1878-0180
J9 J MECH BEHAV BIOMED
JI J. Mech. Behav. Biomed. Mater.
PD DEC
PY 2016
VL 64
BP 10
EP 17
DI 10.1016/j.jmbbm.2016.07.018
PG 8
WC Engineering, Biomedical; Materials Science, Biomaterials
SC Engineering; Materials Science
GA DW3EY
UT WOS:000383526100002
PM 27479890
ER
PT J
AU Grady, C
Fauci, AS
AF Grady, Christine
Fauci, Anthony S.
TI THE ROLE OF THE VIRTUOUS INVESTIGATOR IN PROTECTING HUMAN RESEARCH
SUBJECTS
SO PERSPECTIVES IN BIOLOGY AND MEDICINE
LA English
DT Article
ID CLINICAL-RESEARCH; ETHICS; BOARDS; PHYSICIAN; TRIALS
AB In his famous 1966 New England Journal of Medicine article, Henry Beecher concluded that a critical safeguard for protecting human participants, more reliable than informed consent, was the "presence of an intelligent, informed, conscientious, compassionate, responsible investigator."This article examines Beecher's appeal to reliance on the "virtuous" investigator in light of the critical role that investigators play in research ethics and the systems of research protections that have been developed since Beecher's writing. It addresses the extent to which research ethics rely on virtuous investigators; the meaning of virtuous, as distinct from compliance with the rules and regulations that guide ethical research; the particular virtues that it might be important for investigators to have; and the impact of the existing system of human subjects protections on the virtuous investigator.The virtuous investigator who is motivated to take ethical responsibilities seriously is an essential safeguard for the protection of human research participants and an important complement to the system of oversight protections. However, since the current human subjects protection system does not promote virtue or ethical resourcefulness by investigators, attention to enhancing a culture of professional responsibility might serve to forge a synergy between the protections afforded by the current oversight system and those provided by the virtuous investigator.
C1 [Grady, Christine] NIH, Dept Bioeth, Clin Res Ctr, Bethesda, MD USA.
[Fauci, Anthony S.] NIAID, NIH, Bethesda, MD USA.
RP Grady, C (reprint author), Dept Bioeth, NIH Clin Ctr Bldg 10-1C118, Bethesda, MD 20892 USA.
EM cgrady@nih.gov
NR 41
TC 0
Z9 0
U1 14
U2 19
PU JOHNS HOPKINS UNIV PRESS
PI BALTIMORE
PA JOURNALS PUBLISHING DIVISION, 2715 NORTH CHARLES ST, BALTIMORE, MD
21218-4363 USA
SN 0031-5982
EI 1529-8795
J9 PERSPECT BIOL MED
JI Perspect. Biol. Med.
PD WIN
PY 2016
VL 59
IS 1
BP 122
EP 131
PG 10
WC History & Philosophy Of Science; Medicine, Research & Experimental
SC History & Philosophy of Science; Research & Experimental Medicine
GA DT1MW
UT WOS:000381247800010
PM 27499489
ER
PT J
AU Kim, SYH
AF Kim, Scott Y. H.
TI CLINICAL TRIALS WITHOUT CONSENT?
SO PERSPECTIVES IN BIOLOGY AND MEDICINE
LA English
DT Article
ID INFORMED-CONSENT; RANDOMIZED-TRIALS; PRAGMATIC TRIALS; MINIMAL RISK;
ETHICS; ENROLLMENT; INFANTS
AB Fifty years after Beecher's landmark article, an old question is being debated anew: is it ethical to conduct clinical research without consent? This paper provides a systematic analysis of this question. First, it describes five clinical trials that have either been conducted (or proposed) without the subjects providing consent. Second, it reviews a number of conditions that are often provided to justify bypassing of consent and finds that only some of them qualify as necessary conditions for bypassing consent. When those conditions are applied to the clinical trials, only one trial without consent (a type of cluster randomized trial) appears clearly justified; bypassing consent in the remaining four trials is more questionable. The present analysis may be useful in the interpretation of the current U.S. regulations that provide for waivers and alterations of informed consent.
C1 [Kim, Scott Y. H.] NIH, Dept Bioeth, 10 Ctr Dr,1C118, Bethesda, MD 20892 USA.
RP Kim, SYH (reprint author), NIH, Dept Bioeth, 10 Ctr Dr,1C118, Bethesda, MD 20892 USA.
EM scott.kim@nih.gov
NR 32
TC 0
Z9 0
U1 15
U2 23
PU JOHNS HOPKINS UNIV PRESS
PI BALTIMORE
PA JOURNALS PUBLISHING DIVISION, 2715 NORTH CHARLES ST, BALTIMORE, MD
21218-4363 USA
SN 0031-5982
EI 1529-8795
J9 PERSPECT BIOL MED
JI Perspect. Biol. Med.
PD WIN
PY 2016
VL 59
IS 1
BP 132
EP 146
PG 15
WC History & Philosophy Of Science; Medicine, Research & Experimental
SC History & Philosophy of Science; Research & Experimental Medicine
GA DT1MW
UT WOS:000381247800011
PM 27499490
ER
PT J
AU Rathbun, AM
Shardell, M
Orwig, D
Hebel, JR
Hicks, GE
Beck, T
Hochberg, MC
Magaziner, J
AF Rathbun, Alan M.
Shardell, Michelle
Orwig, Denise
Hebel, J. Richard
Hicks, Gregory E.
Beck, Thomas
Hochberg, Marc C.
Magaziner, Jay
TI Differences in the trajectory of bone mineral density change measured at
the total hip and femoral neck between men and women following hip
fracture
SO ARCHIVES OF OSTEOPOROSIS
LA English
DT Article
DE Aging; DXA; Osteoporosis; Hip fracture; Sex
ID SEMIPARAMETRIC REGRESSION-MODELS; OSTEOPOROTIC FRACTURES; ELDERLY-MEN;
OLDER MEN; PERIOSTEAL APPOSITION; RISK-FACTORS; AGE; DETERMINANTS; MASS;
POPULATION
AB The Summary Research has not examined changes in bone mineral density (BMD) between men and women following hip fracture. The aim was to evaluate sex differences in BMD following hip fracture. Men experienced significant declines in BMD, while not statistically greater than women, underscoring the necessity for better osteoporosis care in men.
Introduction Each year in the USA, approximately 260,000 older adults experience a hip fracture. Women experiencing hip fracture have excess decline in BMD in the year following fracture compared to expected decrements due to aging, but few studies have assessed sex differences in the sequelae of hip fracture. Thus, our objective was to examine sex differences in BMD change in the year after hip fracture.
Methods The sample (n=286) included persons enrolled in the Baltimore Hip Studies 7th cohort, a study that matched (1: 1) men and women experiencing hip fracture. Weighted estimating equations that accounted for missing data and selective survival were used to estimate sex differences in 12-month total hip (TH) and femoral neck (FN) BMD changes.
Results Men had larger average adjusted percent decline in TH and FN BMD. Adjusted 12-month decreases at the FN showed a statistically significant decline of -4.60 % (95 % confidence interval[CI] -7.76 %, -0.20 %) in men and an insignificant change of -1.62 % (95 % CI -4.57 %, 1.32 %) in women. Yet, the difference in change between men and women was not statistically significant (P=0.17). The estimated sex differences for TH BMD loss were smaller in magnitude.
Conclusions There is evidence of significant BMD loss among men at the FN in the year after hip fracture. Although not statistically greater than women, these clinically significant findings highlight the need for improved osteoporosis care among men prior to and after hip fracture.
C1 [Rathbun, Alan M.; Orwig, Denise; Hebel, J. Richard; Hochberg, Marc C.; Magaziner, Jay] Univ Maryland, Sch Med, Dept Epidemiol & Publ Hlth, 660 W Redwood St,Howard Hall Suite 200, Baltimore, MD 21201 USA.
[Shardell, Michelle] NIA, 251 Bayview Blvd, Baltimore, MD 21224 USA.
[Hicks, Gregory E.] Univ Delaware, 540 S Coll Ave,Suite 210E, Newark, DE 19713 USA.
[Beck, Thomas] Beck Radiol Innovat, 922 Rambling Dr, Catonsville, MD 21228 USA.
RP Rathbun, AM (reprint author), Univ Maryland, Sch Med, Dept Epidemiol & Publ Hlth, 660 W Redwood St,Howard Hall Suite 200, Baltimore, MD 21201 USA.
EM arathbun@epi.umaryland.edu
NR 40
TC 1
Z9 1
U1 14
U2 27
PU SPRINGER LONDON LTD
PI LONDON
PA 236 GRAYS INN RD, 6TH FLOOR, LONDON WC1X 8HL, ENGLAND
SN 1862-3522
EI 1862-3514
J9 ARCH OSTEOPOROS
JI Arch. Osteoporos.
PD DEC
PY 2016
VL 11
IS 1
DI 10.1007/s11657-016-0263-6
PG 9
WC Endocrinology & Metabolism; Orthopedics
SC Endocrinology & Metabolism; Orthopedics
GA DP1AU
UT WOS:000378223400009
ER
PT J
AU Chamcha, V
Kannanganat, S
Gangadhara, S
Nabi, R
Kozlowski, PA
Montefiori, DC
LaBranche, CC
Wrammert, J
Keele, BF
Balachandran, H
Sahu, S
Lifton, M
Santra, S
Basu, R
Moss, B
Robinson, HL
Amara, RR
AF Chamcha, Venkateswarlu
Kannanganat, Sunil
Gangadhara, Sailaja
Nabi, Rafiq
Kozlowski, Pamela A.
Montefiori, David C.
LaBranche, Celia C.
Wrammert, Jens
Keele, Brandon F.
Balachandran, Harikrishnan
Sahu, Sujata
Lifton, Michelle
Santra, Sampa
Basu, Rahul
Moss, Bernard
Robinson, Harriet L.
Amara, Rama Rao
TI Strong, but Age-Dependent, Protection Elicited by a Deoxyribonucleic
Acid/Modified Vaccinia Ankara Simian Immunodeficiency Virus Vaccine
SO OPEN FORUM INFECTIOUS DISEASES
LA English
DT Article
DE age-dependent protection; antibody; DNA/MVA vaccine; HIV vaccine; SIV
ID DOSE CHALLENGE EXPERIMENTS; RHESUS MACAQUES; ANTIBODY ACTIVITIES;
IMMUNE-RESPONSES; HIV-1 INFECTION; DNA/MVA VACCINE; SIV CHALLENGES; DNA;
IMMUNOGENICITY; ACQUISITION
AB Background. In this study, we analyzed the protective efficacy of a simian immunodeficiency virus (SIV) macaque 239 (SIVmac239) analogue of the clinically tested GOVX-B11 deoxyribonucleic acid (DNA)/modified vaccinia Ankara (MVA) human immunodeficiency virus vaccine.
Methods. The tested vaccine used a DNA immunogen mutated to mimic the human vaccine and a regimen with DNA deliveries at weeks 0 and 8 and MVA deliveries at weeks 16 and 32. Twelve weekly rectal challenges with 0.3 animal infectious doses of SIV sootey mangabey E660 (SIVsmE660) were administered starting at 6 months after the last immunization.
Results. Over the first 6 rectal exposures to SIVsmE660, <10-year-old tripartite motif-containing protein 5 (TRIM5) alpha-permissive rhesus macaques showed an 80% reduction in per-exposure risk of infection as opposed to a 46% reduction in animals over 10 years old; and, over the 12 challenges, they showed a 72% as opposed to a 10% reduction. Analyses of elicited immune responses suggested that higher antibody responses in the younger animals had played a role in protection.
Conclusions. The simian analogue of the GOVX-B11 HIV provided strong protection against repeated rectal challenges in young adult macaques.
C1 [Chamcha, Venkateswarlu; Kannanganat, Sunil; Gangadhara, Sailaja; Amara, Rama Rao] Emory Univ, Yerkes Natl Primate Res Ctr, Atlanta, GA 30322 USA.
[Nabi, Rafiq; Kozlowski, Pamela A.] Louisiana State Univ, Dept Microbiol Immunol & Parasitol, Hlth Sci Ctr, New Orleans, LA USA.
[Montefiori, David C.; LaBranche, Celia C.] Duke Univ, Med Ctr, Durham, NC USA.
[Wrammert, Jens] Emory Univ, Sch Med, Dept Pediat, Atlanta, GA USA.
[Keele, Brandon F.] Leidos Biomed Res Inc, AIDS & Canc Virus Program, Frederick Natl Lab Canc Res, Baltimore, MD USA.
[Balachandran, Harikrishnan; Sahu, Sujata; Lifton, Michelle; Santra, Sampa] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA.
[Basu, Rahul; Robinson, Harriet L.] Geovax Inc, Smyrna, GA USA.
[Moss, Bernard] NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Amara, RR (reprint author), 954 Gatewood Rd NE, Atlanta, GA 30329 USA.
EM ramara@emory.edu
NR 41
TC 1
Z9 1
U1 33
U2 47
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 2328-8957
J9 OPEN FORUM INFECT DI
JI Open Forum Infect. Dis.
PD WIN
PY 2016
VL 3
IS 1
DI 10.1093/ofid/ofw034
PG 10
WC Infectious Diseases
SC Infectious Diseases
GA DJ4QB
UT WOS:000374190900074
ER
PT J
AU Gamaletsou, MN
Rammaert, B
Bueno, MA
Sipsas, NV
Moriyama, B
Kontoyiannis, DP
Roilides, E
Zeller, V
Taj-Aldeen, SJ
Miller, AO
Petraitiene, R
Lortholary, O
Walsh, TJ
AF Gamaletsou, Maria N.
Rammaert, Blandine
Bueno, Marimelle A.
Sipsas, Nikolaos V.
Moriyama, Brad
Kontoyiannis, Dimitrios P.
Roilides, Emmanuel
Zeller, Valerie
Taj-Aldeen, Saad J.
Miller, Andy O.
Petraitiene, Ruta
Lortholary, Olivier
Walsh, Thomas J.
CA Int Osteoarticular Mycoses Consort
TI Candida Arthritis: Analysis of 112 Pediatric and Adult Cases
SO OPEN FORUM INFECTIOUS DISEASES
LA English
DT Article
DE antifungal therapy; arthritis; Candida spp; diagnosis; invasive
candidiasis
ID TOTAL KNEE ARTHROPLASTY; OF-THE-LITERATURE; FUNGAL OSTEOARTICULAR
INFECTIONS; ACUTE MYELOGENOUS LEUKEMIA; ALBICANS SEPTIC ARTHRITIS;
LIPOSOMAL AMPHOTERICIN-B; RENAL-TRANSPLANT PATIENT; SYSTEMIC
CANDIDIASIS; TROPICALIS ARTHRITIS; KRUSEI ARTHRITIS
AB Background. Candida arthritis is a debilitating form of deeply invasive candidiasis. However, its epidemiology, clinical manifestations, management, and outcome are not well understood.
Methods. Cases of Candida arthritis were reviewed from 1967 through 2014. Variables included Candida spp in joint and/or adjacent bone, underlying conditions, clinical manifestations, inflammatory biomarkers, diagnostic imaging, management, and outcome.
Results. Among 112 evaluable cases, 62% were males and 36% were pediatric. Median age was 40 years (range, <1-84 years). Most patients (65%) were not pharmacologically immunosuppressed. Polyarticular infection (>3 joints) occurred in 31% of cases. Clinical manifestations included pain (82%), edema (71%), limited function (39%), and erythema (22%) with knees (75%) and hips (15%) most commonly infected. Median erythrocyte sedimentation rate was 62 mm/hr (10-141) and C reactive protein 26 mg/dL (0.5-95). Synovial fluid median white blood cell count was 27 500/ttL (range, 100-220 000/ttL) with 90% polymorphonuclear neutrophils (range, 24-98). Adjacent osteomyelitis was present in 30% of cases. Candida albicans constituted 63%, Candida tropicalis 14%, and Candida parapsilosis 11%. Most cases (66%) arose de novo, whereas 34% emerged during antifungal therapy. Osteolysis occurred in 42%, joint -effusion in 31%, and soft tissue extension in 21%. Amphotericin and fluconazole were the most commonly used agents. Surgical interventions included debridement in 25%, irrigation 10%, and drainage 12%. Complete or partial response was achieved in 96% and relapse in 16%.
Conclusion. Candida arthritis mainly emerges as a de novo infection in usually non-immunosuppressed patients with hips and knees being most commonly infected. Localizing symptoms are frequent, and the most common etiologic agents are C albicans, C tropicalis, and C parapsilosis. Management of Candida arthritis remains challenging with a clear risk of relapse, despite antifungal therapy.
C1 [Gamaletsou, Maria N.; Bueno, Marimelle A.; Miller, Andy O.; Petraitiene, Ruta; Walsh, Thomas J.] Cornell Univ, Weill Cornell Med, Dept Med, New York, NY 10021 USA.
[Gamaletsou, Maria N.; Bueno, Marimelle A.; Miller, Andy O.; Petraitiene, Ruta; Walsh, Thomas J.] Cornell Univ, Weill Cornell Med, Dept Pediat, New York, NY 10021 USA.
[Gamaletsou, Maria N.; Bueno, Marimelle A.; Miller, Andy O.; Petraitiene, Ruta; Walsh, Thomas J.] Cornell Univ, Weill Cornell Med, Dept Microbiol & Immunol, New York, NY 10021 USA.
[Gamaletsou, Maria N.; Sipsas, Nikolaos V.] Natl & Kapodistrian & Univ Athens, Athens, Greece.
[Gamaletsou, Maria N.; Sipsas, Nikolaos V.; Roilides, Emmanuel; Miller, Andy O.; Lortholary, Olivier; Walsh, Thomas J.] Hosp Special Surg, Ctr Osteoarticular Mycoses, 535 E 70th St, New York, NY 10021 USA.
[Rammaert, Blandine; Lortholary, Olivier] Univ Paris 05, Hop Necker Enfants Malad, AP HP,Inst Imagine, Sorbonne Paris Cite,Serv Malad Infect & Trop,Ctr, Paris, France.
[Rammaert, Blandine] Inst Pasteur, Unite Mycol Mol, Paris, France.
[Moriyama, Brad] NIH, Dept Pharm, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA.
[Kontoyiannis, Dimitrios P.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Roilides, Emmanuel] Aristotle Univ Thessaloniki, Sch Hlth Sci, Dept Pediat 3, Thessaloniki, Greece.
[Roilides, Emmanuel] Hippokrateion Hosp, Thessaloniki, Greece.
[Zeller, Valerie] Grp Hosp Diaconesses Croix St Simon, Osteoarticular Reference Ctr, Paris, France.
[Taj-Aldeen, Saad J.] Univ Doha, Mycol Lab, Doha, Qatar.
[Miller, Andy O.] Hosp Special Surg, 535 E 70th St, New York, NY 10021 USA.
RP Walsh, TJ (reprint author), Weill Cornell Med Ctr, Transplantat Oncol Infect Dis Program, 1300 York Ave,A-421, New York, NY 10065 USA.; Walsh, TJ (reprint author), Weill Cornell Med Ctr, Infect Dis Translat Res Lab, 1300 York Ave,A-421, New York, NY 10065 USA.; Walsh, TJ (reprint author), New York Presbyterian Hosp, 1300 York Ave,A-421, New York, NY 10065 USA.
EM thw2003@med.cornell.edu
NR 112
TC 0
Z9 0
U1 24
U2 69
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 2328-8957
J9 OPEN FORUM INFECT DI
JI Open Forum Infect. Dis.
PD WIN
PY 2016
VL 3
IS 1
DI 10.1093/ofid/ofv207
PG 10
WC Infectious Diseases
SC Infectious Diseases
GA DJ4QB
UT WOS:000374190900027
ER
PT J
AU Nolte, T
Brander-Weber, P
Dangler, C
Deschl, U
Elwell, MR
Greaves, P
Hailey, R
Leach, MW
Pandiri, AR
Rogers, A
Shackelford, CC
Spencer, A
Tanaka, T
Ward, JM
AF Nolte, Thomas
Brander-Weber, Patricia
Dangler, Charles
Deschl, Ulrich
Elwell, Michael R.
Greaves, Peter
Hailey, Richard
Leach, Michael W.
Pandiri, Arun R.
Rogers, Arlin
Shackelford, Cynthia C.
Spencer, Andrew
Tanaka, Takuji
Ward, Jerrold M.
TI Nonproliferative and Proliferative Lesions of the Gastrointestinal
Tract, Pancreas and Salivary Glands of the Rat and Mouse
SO JOURNAL OF TOXICOLOGIC PATHOLOGY
LA English
DT Article
DE diagnostic pathology; nomenclature; diagnostic criteria; digestive
system or tract; oral cavity; esophagus; stomach; intestine; small
intestine; large intestine; salivary glands; pancreas se
ID SPRAGUE-DAWLEY RATS; LARGE-BOWEL DISEASE; SUBMANDIBULAR-GLAND;
ACINAR-CELL; EXOCRINE PANCREAS; TRANSGENIC MICE; WISTAR RATS;
ANIMAL-MODELS; DUCTAL ADENOCARCINOMA; PAROTID-GLANDS
AB The INHAND (International Harmonization of Nomenclature and Diagnostic Criteria for Lesions in Rats and Mice) project is a joint initiative of the Societies of Toxicologic Pathology from Europe (ESTP), Great Britain (BSTP), Japan (JSTP), and North America (STP) to develop an internationally accepted nomenclature and diagnostic criteria for nonproliferative and proliferative lesions in laboratory animals. The purpose of this publication is to provide a standardized nomenclature and diagnostic criteria for classifying lesions in the digestive system including the salivary glands and the exocrine pancreas of laboratory rats and mice. Most lesions are illustrated by color photomicrographs. The standardized nomenclature, the diagnostic criteria, and the photomicrographs are also available electronically on the Internet (http://www.goreni.org/). Sources of material included histopathology databases from government, academia, and industrial laboratories throughout the world. Content includes spontaneous and age related lesions as well as lesions induced by exposure to test items. Relevant infectious and parasitic lesions are included as well. A widely accepted and utilized international harmonization of nomenclature and diagnostic criteria for the digestive system will decrease misunderstandings among regulatory and scientific research organizations in different countries and provide a common language to increase and enrich international exchanges of information among toxicologists and pathologists.
C1 [Nolte, Thomas; Deschl, Ulrich] Boehringer Ingelheim Pharma GmbH & Co KG, D-88397 Biberach, Germany.
[Brander-Weber, Patricia] Novartis Pharma AG, Novartis Inst BioMed Res, CH-4002 Basel, Switzerland.
[Dangler, Charles] Jackson Lab, 600 Main St, Bar Harbor, ME 04609 USA.
[Dangler, Charles] Sanofi5, Mt Rd, Framingham, MA 01740 USA.
[Elwell, Michael R.] Covance Labs Inc, 14500 Avion Pkwy,Ste 125, Chantilly, VA 20151 USA.
[Greaves, Peter] Univ Leicester, Leicester Royal Infirm, Dept Canc Studies & Mol Med, Robert Kilpatrick Clin Sci Bldg, Leicester LE2 7LX, Leics, England.
[Hailey, Richard] GlaxoSmithKline, POB 14164, Durham, NC 27709 USA.
[Leach, Michael W.] Pfizer Inc, One Burtt Rd, Andover, MA 01810 USA.
[Pandiri, Arun R.; Shackelford, Cynthia C.] NIEHS, Cellular & Mol Pathol Branch, Natl Toxicol Program, POB 12233, Res Triangle Pk, NC 27709 USA.
[Pandiri, Arun R.] Expt Pathol Labs Inc, POB 12766, Res Triangle Pk, NC 27709 USA.
[Rogers, Arlin] Tufts Univ, Dept Biomed Sci, 274 Tremont St, Boston, MA 02111 USA.
[Spencer, Andrew] Covance Labs Ltd, Alnwick Res Ctr, Willowburn Ave, Alnwick NE66 2JH, Northd, England.
[Tanaka, Takuji] Gifu Municipal Hosp, Gifu 5008285, Japan.
[Ward, Jerrold M.] Global VetPathol, Montgomery Village, MD USA.
RP Nolte, T (reprint author), Boehringer Ingelheim Pharma GmbH & Co KG, D-88397 Biberach, Germany.
EM thomas.nolte@boehringer-ingelheim.com
RI yilmaz, kevser/E-1917-2016
NR 287
TC 1
Z9 1
U1 27
U2 182
PU JAPANESE SOC TOXICOLOGIC PATHOLOGY
PI TOKYO
PA DEPT ACAD SOC, MEDICAL TRIBUNE INC, ITALIAN CULTURAL INST BLDG 8F
2-1-30, KUDAN MINAMI, CHIYODA, TOKYO, 102-0074, JAPAN
SN 0914-9198
EI 1881-915X
J9 J TOXICOL PATHOL
JI J. Toxicol. Pathol.
PD WIN
PY 2016
VL 29
IS 1
SU S
BP 1S
EP 124S
DI 10.1293/tox.29.1S
PG 124
WC Pathology; Toxicology
SC Pathology; Toxicology
GA DD7NE
UT WOS:000370110600001
PM 26973378
ER
PT J
AU Kinoshita, Y
Yoshizawa, K
Emoto, Y
Yuki, M
Yuri, T
Shikata, N
Elmore, SA
Tsubura, A
AF Kinoshita, Yuichi
Yoshizawa, Katsuhiko
Emoto, Yuko
Yuki, Michiko
Yuri, Takashi
Shikata, Nobuaki
Elmore, Susan A.
Tsubura, Airo
TI A spontaneously occurring malignant ovarian Sertoli cell tumor in a
young Sprague Dawley rat
SO JOURNAL OF TOXICOLOGIC PATHOLOGY
LA English
DT Article
DE immunohistochemistry; malignant tumor; ovary; Sertoli cell; spontaneous;
young rat
ID LESIONS; NEOPLASMS; MICE
AB Primary ovarian tumors are generally uncommon in rats used in toxicologic studies. A malignant Sertoli cell tumor was present in the ovary of a 19-week-old female Sprague Dawley rat. Macroscopically, the mass was white and firm, 10 x 13 x 17 mm in size, and located in the right ovary. Histopathologically, the mass was composed of nests of pleomorphic cells, which formed seminiferous-like tubules separated by a thin fibrovascular stroma. The tubules were lined by tumor cells, which had basally located nuclei and abundant eosinophilic and vacuolated cytoplasm. In some areas, the tumor cells were arranged in a retiform growth pattern, mimicking a rete testis/ovarii. Disseminated metastases to the surfaces of the mesentery, spleen and liver were also present. Immunohistochemically, many tumor cells were strongly positive for vimentin, estrogen receptor a and Ki 67. Some tumor cells were positive for pancytokeratin and inhibin a. These findings closely resemble those of an ovarian-derived human malignant Sertoli cell tumor. From our review of the literature, we believe this is the first report of a spontaneous malignant Sertoli cell tumor in the ovary of a young laboratory rat. This case might provide useful historical control information for rat toxicity studies.
C1 [Kinoshita, Yuichi; Yoshizawa, Katsuhiko; Emoto, Yuko; Yuki, Michiko; Yuri, Takashi; Tsubura, Airo] Kansai Med Univ, Dept Pathol 2, 2-5-1 Shin Machi, Hirakata, Osaka 5731010, Japan.
[Kinoshita, Yuichi; Shikata, Nobuaki] Kansai Med Univ, Takii Hosp, Div Diagnost Cytopathol & Histopathol, Fumizono 10-15, Moriguchi, Osaka 5708507, Japan.
[Elmore, Susan A.] Natl Inst Environm Hlth Sci, Cellular & Mol Pathol Branch, 111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA.
RP Yoshizawa, K (reprint author), Kansai Med Univ, Dept Pathol 2, 2-5-1 Shin Machi, Hirakata, Osaka 5731010, Japan.
EM yoshizak@hirakata.kmu.co.jp
FU MEXT
FX The authors would like to thank Dr. Darlene Dixon of the Molecular
Pathogenesis Group, National Toxicology Program Laboratory, National
Toxicology Program, National Institute of Environmental Health Sciences,
National Institutes of Health, USA, and Dr. Tomo Sasaki and Dr. Takayasu
Moroki, Department of Toxicological Research, Research Laboratories,
Maruho Co. Ltd., Japan, for their review and critical discussion of this
case. In connection with this paper, there is no conflict of interest
with any of the author's companies to be disclosed. This project was
supported by a grant from MEXT-Supported Programs for the Strategic
Research Foundations at Private Universities.
NR 27
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Z9 1
U1 52
U2 119
PU JAPANESE SOC TOXICOLOGIC PATHOLOGY
PI TOKYO
PA DEPT ACAD SOC, MEDICAL TRIBUNE INC, ITALIAN CULTURAL INST BLDG 8F
2-1-30, KUDAN MINAMI, CHIYODA, TOKYO, 102-0074, JAPAN
SN 0914-9198
EI 1881-915X
J9 J TOXICOL PATHOL
JI J. Toxicol. Pathol.
PD WIN
PY 2016
VL 29
IS 1
BP 53
EP 59
DI 10.1293/tox.2015-0057
PG 7
WC Pathology; Toxicology
SC Pathology; Toxicology
GA DC9TZ
UT WOS:000369565300008
PM 26989303
ER
PT J
AU Malecki, M
Putzer, E
Quach, C
Dodivenaka, C
Tombokan, X
AF Malecki, Marek
Putzer, Emily
Quach, Caroline
Dodivenaka, Chaitanya
Tombokan, Xenia
TI Novel paradigm for immunotherapy of ovarian cancer by engaging
prophylactic immunity against hepatitis B virus
SO CLINICAL AND TRANSLATIONAL MEDICINE
LA English
DT Article
ID SURFACE-ANTIGEN; OVEREXPRESSION; CELLS; HER-2/NEU; SURVIVAL; SINGLE;
YEAST
AB Background: Only eight women out of one hundred diagnosed with ovarian epithelial cancers, which progressed to the clinical stage IV, survive 10 years. First line therapies: surgery, chemotherapy, and radiation therapy inflict very serious iatrogenic consequences. Passive immunotherapy of ovarian cancers offers only low efficacy. Prophylactic and therapeutic vaccines for ovarian cancers are not available. Interestingly, prophylactic vaccines for Hepatitis B Viruses (HBV) are very effective.
Specific aim: The specific aim of this work was to design, synthesize, and administer biomolecules, which would engage prophylactic, vaccination-induced immunity for HBV towards killing of ovarian cancer cells with high specificity and efficacy.
Patients: Tissue biopsies, ascites, and blood were acquired from the patients, whose identities were entirely concealed in accordance with the Declaration of Helsinki, pursuant to the Institutional Review Board approval, and with the Patients' informed consent.
Methods and results: By biomolecular engineering, we have created a novel family of biomolecules: antibody x vaccine engineered constructs (AVEC: anti-HER-2 x HBsAg). We have collected the blood from the volunteers, and measured the titers of anti-HBV antibodies resulting from the FDA approved and CDC scheduled HBV vaccinations. We have acquired tumor biopsies, ascites, and blood from patients suffering from the advanced ovarian cancers. We have established cultures of HER-2 over-expressing epithelial ovarian cancers: OV-90, TOC-112D, SKOV-3, as well as human ovary surface epithelial (HOSE) and human artery endothelial (HAE) cells. Treatment of the HER-2+ ovarian cancer cells with AVEC: anti-HER-2 x HBsAg, accompanied by administration of blood drawn from patients with high titers of the anti-HBV antibodies, resulted in much higher therapeutic efficacy as compared to treatment with the naked anti-HER-2 antibodies alone and/or with the relevant isotype antibodies. This treatment had practically no effect upon the HOSE and HAE cells.
Discussion: Herein, we report attaining the great improvement in eradication efficacy of ovarian epithelial cancer cells' by engaging prophylactic immunity against HBV; thus creating a novel paradigm for immunotherapy of ovarian cancer. We have accomplished that by designing, synthesis, and administration of AVEC. Therefore, the HBV vaccination acquired immunity mounts immune response against the vaccine, but AVEC redirect, accelerate, and amplify this immune response of all the elements of the native and adaptive immune system against ovarian cancer. Our novel paradigm of immunotherapy is currently streamlined to clinical trials also of other cancers, while also engaging prophylactic and acquired immunity.
Conclusion: Novel antibody-vaccine engineered constructs (AVEC) create the solid foundation for redirected, accelerated, and amplified prophylactic, HBV vaccination-induced immunity immunotherapy (RAAVIIT) of ovarian cancers.
C1 [Malecki, Marek] Phoenix Biomol Engn Fdn, San Francisco, CA 94119 USA.
[Malecki, Marek] Univ Wisconsin, Madison, WI 53706 USA.
[Malecki, Marek] NIH, Natl Magnet Resonance Facil, Madison, WI 53706 USA.
[Putzer, Emily] Dept Hlth, Washington, DC USA.
[Quach, Caroline] Long Isl Univ, Brookville, NY USA.
[Dodivenaka, Chaitanya] South Dakota State Univ, Brookings, SD 57007 USA.
[Tombokan, Xenia] Bruker Biospin Corp, The Woodlands, TX USA.
RP Malecki, M (reprint author), Phoenix Biomol Engn Fdn, San Francisco, CA 94119 USA.; Malecki, M (reprint author), Univ Wisconsin, Madison, WI 53706 USA.; Malecki, M (reprint author), NIH, Natl Magnet Resonance Facil, Madison, WI 53706 USA.
EM mm@PBMEF.org
FU PBMEF [2006070101]; NSF [9420056, 9522771, 9902020, 0094016]; NIH [P41
RR000570, P41 RR002301]
FX Parts of this work were supported by the funds from the PBMEF
(2006070101), the NSF (9420056, 9522771, 9902020, and 0094016), the NIH
(P41 RR000570 and P41 RR002301); to Marek Malecki MD. Ph.D.-the
principal investigator. Administrators of the funding institutions had
no influence on the data acquisition and the IP.
NR 19
TC 0
Z9 0
U1 1
U2 1
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 2001-1326
J9 CLIN TRANSL MED
JI Clin. Transl. Med.
PD NOV 30
PY 2016
VL 5
AR 44
DI 10.1186/s40169-016-0125-2
PG 16
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA EH7KR
UT WOS:000391952300001
PM 27905089
ER
PT J
AU da Cunha, MG
Francob, GCN
Franchin, M
Beutler, JA
de Alencar, SM
Ikegaki, M
Rosalen, PL
AF da Cunha, Marcos Guilherme
Nobre Francob, Gilson Cesar
Franchin, Marcelo
Beutler, John A.
de Alencar, Severino Matias
Ikegaki, Masaharu
Rosalen, Pedro Luiz
TI Prediction of pharmacokinetic and toxicological parameters of a
4-phenylcoumarin isolated from geopropolis: In silico and in vitro
approaches
SO TOXICOLOGY LETTERS
LA English
DT Article
DE In silico; in vitro; Pharmacokinetics; Genotoxicity; Coumarin;
Geopropolis
ID MELIPONA-SCUTELLARIS; DRUG-METABOLISM; MISMATCH REPAIR; CISPLATIN;
APOPTOSIS; TOXICITY; PRODUCTS; SYSTEM; CELLS
AB In silico and in vitro methodologies have been used as important tools in the drug discovery process, including from natural sources. The aim of this study was to predict pharmacokinetic and toxicity (ADME/Tox) properties of a coumarin isolated from geopropolis using in silico and in vitro approaches. Cinnamoyloxy-mammeisin (CNM) isolated from Brazilian M. scutellaris geopropolis was evaluated for its pharmacokinetic parameters by in silico models (ACD/Percepta (TM) and MetaDrug (TM) software). Genotoxicity was assessed by in vitro DNA damage signaling PCR array. CNM did not pass all parameters of Lipinski's rule of five, with a predicted low oral bioavailability and high plasma protein binding, but with good predicted blood brain barrier penetration. CNM was predicted to show low affinity to cytochrome P450 family members. Furthermore, the predicted Ames test indicated potential mutagenicity of CNM. Also, the probability of toxicity for organs and tissues was classified as moderate and high for liver and kidney, and moderate and low for skin and eye irritation, respectively. The PCR array analysis showed that CNM significantly upregulated about 7% of all DNA damage-related genes. By exploring the biological function of these genes, it was found that the predicted CNM genotoxicity is likely to be mediated by apoptosis. The predicted ADME/Tox profile suggests that external use of CNM may be preferable to systemic exposure, while its genotoxicity was characterized by the upregulation of apoptosis-related genes after treatment. The combined use of in silico and in vitro approaches to evaluate these parameters generated useful hypotheses to guide further preclinical studies. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
C1 [da Cunha, Marcos Guilherme; Franchin, Marcelo; Rosalen, Pedro Luiz] Univ Campinas UNICAMP, Piracicaba Dent Sch, Dept Physiol Sci, Campinas, SP, Brazil.
[Nobre Francob, Gilson Cesar] Univ Estadual Ponta Grossa, Dept Gen Biol, Lab Physiol & Pathophysiol, Ponta Grossa, PR, Brazil.
[da Cunha, Marcos Guilherme; Beutler, John A.] NCI, Mol Targets Lab, NIH, Frederick, MD 21701 USA.
[de Alencar, Severino Matias] Univ Sao Paulo, Luiz de Queiroz Coll Agr, Dept Agri Food Ind Food & Nutr, Piracicaba, SP, Brazil.
[Ikegaki, Masaharu] Univ Fed Alfenas, Coll Pharmaceut Sci, Alfenas, MG, Brazil.
RP Rosalen, PL (reprint author), Univ Campinas UNICAMP, Piracicaba Dent Sch, Dept Physiol Sci, Campinas, SP, Brazil.
EM rosalen@fop.unicamp.br
FU Intramural Research Program of the NIH, National Cancer Institute,
Center for Cancer Research; FAPESP [2011/23635-6, 2012/22002-2]
FX This research was supported by the Intramural Research Program of the
NIH, National Cancer Institute, Center for Cancer Research and by FAPESP
(#2011/23635-6 and #2012/22002-2).
NR 31
TC 0
Z9 0
U1 3
U2 3
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0378-4274
EI 1879-3169
J9 TOXICOL LETT
JI Toxicol. Lett.
PD NOV 30
PY 2016
VL 263
BP 6
EP 10
DI 10.1016/j.toxlet.2016.10.010
PG 5
WC Toxicology
SC Toxicology
GA EF7CR
UT WOS:000390488200002
PM 27773722
ER
PT J
AU Lee, SB
Mao, A
Bhattacharya, S
Robertson, N
Grisshammer, R
Tate, CG
Vaidehit, N
AF Lee, Sangbae
Mao, Allen
Bhattacharya, Supriyo
Robertson, Nathan
Grisshammer, Reinhard
Tate, Christopher G.
Vaidehit, Nagarajan
TI How Do Short Chain Nonionic Detergents Destabilize G-Protein-Coupled
Receptors?
SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Article
ID ADENOSINE A(2A) RECEPTOR; PHOTOSYNTHETIC REACTION-CENTER; INTEGRAL
MEMBRANE-PROTEINS; PARTICLE MESH EWALD; ESCHERICHIA-COLI;
MOLECULAR-DYNAMICS; RHODOPSEUDOMONAS-VIRIDIS; STRUCTURAL BASIS;
CRYSTALLIZATION; AGONIST
AB Stability of detergent-solubilized G-protein coupled receptors (GPCRs) is crucial for their purification in a biologically relevant state, and it is well-known that short chain detergents such as octylglucoside are more denaturing than long chain detergents such as dodecylmaltoside. However, the molecular basis for this phenomenon is poorly understood. To gain insights into the mechanism of detergent destabilization of GPCRs, we used atomistic molecular dynamics simulations of thermostabilized adenosine receptor (A(2A)R) mutants embedded in either a lipid bilayer or detergent micelles of alkylmaltosides and alkylglucosides. A(2A)R mutants in dodecylmaltoside or phospholipid showed low flexibility and good interhelical packing. In contrast, A(2A)R mutants in either octylglucoside or nonylglucoside showed decreased alpha-helicity in transmembrane regions, decreased alpha-helical packing, and the interpenetration of detergent molecules between transmembrane alpha-helices. This was not observed in octylglucoside containing phospholipid. Cholesteryl hemisuccinate in dodecylmaltoside increased the energetic stability of the receptor by wedging into crevices on the hydrophobic surface of A(2A)R, increasing packing interactions within the receptor and stiffening the detergent micelle. The data suggest a three-stage process for the initial events in the destabilization of GPCRs by octylglucoside: (i) highly mobile detergent molecules form small micelles around the receptor; (ii) loss of alpha-helicity and decreased interhelical packing interactions in transmembrane regions are promoted by increased receptor thermal motion; (iii) transient separation of transmembrane helices allowed penetration of detergent molecules into the core of the receptor. The relative hydration of the headgroup and alkyl chain correlates with detergent harshness and suggests new avenues to develop milder versions of octylglucoside for receptor crystallization.
C1 [Lee, Sangbae; Mao, Allen; Bhattacharya, Supriyo; Vaidehit, Nagarajan] City Hope Natl Med Ctr, Beckman Res Inst, Dept Mol Immunol, 1500 E Duarte Rd, Duarte, CA 91010 USA.
[Robertson, Nathan] Heptares Therapeut Ltd, BioPk,Broadwater Rd, Welwyn Garden City AL7 3AX, Herts, England.
[Grisshammer, Reinhard] NINDS, Membrane Prot Struct Funct Unit, NIH, US Dept HHS, Rockville, MD 20852 USA.
[Tate, Christopher G.] MRC, Mol Biol Lab, Cambridge Biomed Campus,Francis Crick Ave, Cambridge CB2 0QH, England.
RP Vaidehit, N (reprint author), City Hope Natl Med Ctr, Beckman Res Inst, Dept Mol Immunol, 1500 E Duarte Rd, Duarte, CA 91010 USA.; Tate, CG (reprint author), MRC, Mol Biol Lab, Cambridge Biomed Campus,Francis Crick Ave, Cambridge CB2 0QH, England.
EM cgt@mrc-lmb.cam.ac.uk; NVaidehi@coh.org
FU NIH [R01-GM097261]; Medical Research Council [MC_U105197215]; ERC [EMPSI
339995]; National Institutes of Health, National Institute of
Neurological Disorders and Stroke
FX This work was funded by NIH Grant R01-GM097261 to N.V. Work on GPCRs in
C.G.T.'s lab is funded by the Medical Research Council (MC_U105197215)
and an ERC Advanced Grant (EMPSI 339995). R.G. is supported by the
Intramural Research Program of the National Institutes of Health,
National Institute of Neurological Disorders and Stroke.
NR 78
TC 0
Z9 0
U1 4
U2 4
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0002-7863
J9 J AM CHEM SOC
JI J. Am. Chem. Soc.
PD NOV 30
PY 2016
VL 138
IS 47
BP 15425
EP 15433
DI 10.1021/jacs.6b08742
PG 9
WC Chemistry, Multidisciplinary
SC Chemistry
GA ED8ZV
UT WOS:000389160500020
PM 27792324
ER
PT J
AU Cong, Y
Dyall, J
Hart, BJ
DeWald, LE
Johnson, JC
Postnikova, E
Zhou, H
Gross, R
Rojas, O
Alexander, I
Josleyn, N
Zhang, T
Michelotti, J
Janosko, K
Glass, PJ
Flint, M
McMullan, LK
Spiropoulou, CF
Mierzwa, T
Guha, R
Shinn, P
Michael, S
Klumpp-Thomas, C
McKnight, C
Thomas, C
Eakin, AE
O'Loughlin, KG
Green, CE
Catz, P
Mirsalis, JC
Honko, AN
Olinger, GG
Bennett, RS
Holbrook, MR
Hensley, LE
Jahrling, PB
AF Cong, Yu
Dyall, Julie
Hart, Brit J.
DeWald, Lisa Evans
Johnson, Joshua C.
Postnikova, Elena
Zhou, Huanying
Gross, Robin
Rojas, Oscar
Alexander, Isis
Josleyn, Nicole
Zhang, Tengfei
Michelotti, Julia
Janosko, Krisztina
Glass, Pamela J.
Flint, Mike
McMullan, Laura K.
Spiropoulou, Christina F.
Mierzwa, Tim
Guha, Rajarshi
Shinn, Paul
Michael, Sam
Klumpp-Thomas, Carleen
McKnight, Crystal
Thomas, Craig
Eakin, Ann E.
O'Loughlin, Kathleen G.
Green, Carol E.
Catz, Paul
Mirsalis, Jon C.
Honko, Anna N.
Olinger, Gene G., Jr.
Bennett, Richard S.
Holbrook, Michael R.
Hensley, Lisa E.
Jahrling, Peter B.
TI Evaluation of the Activity of Lamivudine and Zidovudine against Ebola
Virus
SO PLOS ONE
LA English
DT Article
ID REVERSE-TRANSCRIPTASE; CELL-LINES; MACROPHAGES; 5'-TRIPHOSPHATE;
GLYCOPROTEINS; PATHOGENESIS; PREVENTION; DIAGNOSIS; SYNERGY; ENTRY
AB In the fall of 2014, an international news agency reported that patients suffering from Ebola virus disease (EVD) in Liberia were treated successfully with lamivudine, an antiviral drug used to treat human immunodeficiency virus-1 and hepatitis B virus infections. According to the report, 13 out of 15 patients treated with lamivudine survived and were declared free from Ebola virus disease. In this study, the anti-Ebola virus (EBOV) activity of lamivudine and another antiretroviral, zidovudine, were evaluated in a diverse set of cell lines against two variants of wild-type EBOV. Variable assay parameters were assessed to include different multiplicities of infection, lengths of inoculation times, and durations of dosing. At a multiplicity of infection of 1, lamivudine and zidovudine had no effect on EBOV propagation in Vero E6, Hep G2, or HeLa cells, or in primary human monocyte-derived macrophages. At a multiplicity of infection of 0.1, zidovudine demonstrated limited anti-EBOV activity in Huh 7 cells. Under certain conditions, lamivudine had low anti-EBOV activity at the maximum concentration tested (320 mu M). However, lamivudine never achieved greater than 30% viral inhibition, and the activity was not consistently reproducible. Combination of lamivudine and zidovudine showed no synergistic antiviral activity. Independently, a set of in vitro experiments testing lamivudine and zidovudine for antiviral activity against an Ebolaen-hanced green fluorescent protein reporter virus was performed at the Centers for Disease Control and Prevention. No antiviral activity was observed for either compound. A study evaluating the efficacy of lamivudine in a guinea pig model of EVD found no survival benefit. This lack of benefit was observed despite plasma lamivudine concentrations in guinea pig of about 4 mu g/ml obtained in a separately conducted pharmacokinetics study. These studies found no evidence to support the therapeutic use of lamivudine for the treatment of EVD.
C1 [Cong, Yu; Dyall, Julie; Hart, Brit J.; DeWald, Lisa Evans; Johnson, Joshua C.; Postnikova, Elena; Zhou, Huanying; Gross, Robin; Rojas, Oscar; Alexander, Isis; Josleyn, Nicole; Zhang, Tengfei; Michelotti, Julia; Janosko, Krisztina; Honko, Anna N.; Olinger, Gene G., Jr.; Bennett, Richard S.; Holbrook, Michael R.; Hensley, Lisa E.; Jahrling, Peter B.] NIAID, Div Clin Res, Integrated Res Facil, NIH, Frederick, MD 21702 USA.
[Josleyn, Nicole; Glass, Pamela J.] US Army, Med Res Inst Infect Dis, Frederick, MD USA.
[Flint, Mike; McMullan, Laura K.; Spiropoulou, Christina F.] Ctr Dis Control & Prevent, Viral Special Pathogens Branch, Div High Consequence Pathogens & Pathol, Atlanta, GA USA.
[Mierzwa, Tim; Guha, Rajarshi; Shinn, Paul; Michael, Sam; Klumpp-Thomas, Carleen; McKnight, Crystal; Thomas, Craig] NIH, Natl Ctr Adv Translat Sci, Bldg 10, Bethesda, MD 20892 USA.
[Eakin, Ann E.] NIAID, Off Biodef Res Resources & Translat Res, Div Microbiol & Infect Dis, NIH, Rockville, MD USA.
[O'Loughlin, Kathleen G.; Green, Carol E.; Catz, Paul; Mirsalis, Jon C.] SRI Int, 333 Ravenswood Ave, Menlo Pk, CA 94025 USA.
[Jahrling, Peter B.] NIAID, Emerging Viral Pathogens Sect, NIH, Frederick, MD USA.
[Hart, Brit J.] Assoc Publ Hlth Abstract Labs, Silver Spring, MD USA.
[Zhang, Tengfei] Thermo Fisher Sci Inc, Frederick, MD USA.
RP Dyall, J (reprint author), NIAID, Div Clin Res, Integrated Res Facil, NIH, Frederick, MD 21702 USA.
EM dyallj@niaid.nih.gov
OI Honko, Anna/0000-0001-9165-148X; Bennett, Richard/0000-0002-7227-4831
FU SRI International
FX SRI International provided support in the form of salaries for authors
[KGO, PC, CEG, JCM], but did not have any additional role in the study
design, data collection and analysis, decision to publish, or
preparation of the manuscript. The specific roles of these authors are
articulated in the 'author contributions' section.; We thank IRF Cell
Culture staff in preparing the cells used in this study. We appreciate
the strong support from Will Sheffield from NCI-Frederick research donor
program and Linda Coe (IRF) in obtaining fresh human blood from NIH
blood bank (Bethesda, MD, USA). We thank Dr. Gary Kobinger (Public
Health Agency of Canada, Winnipeg, CA) for the Makona variant of EBOV
(GenBank accession no. KP096420). We thank Dr. Thomas Geisbert
(University of Texas Medical Branch at Galveston, Galveston, TX, USA)
for the Hartley guinea pig adapted variant of EBOV. We thank Dr.
Atsunobu Hiraoka (SCGF Research Laboratory, Kyoto, JP) for the kind gift
of conditioned medium from KPB-M15 cells. We thank Dr. Hideki Ebihara
(NIAID, Rocky Mountain Laboratories, Hamilton, MT) for Huh 7 (human
hepatocellular carcinoma) cells. We thank Dr. William Eugene Dowling
(Division of Microbiology and Infectious Diseases, NIH) for providing
resources for the pharmacokinetic study. We thank Linh Nguyen and Julie
Nop for expert technical assistance in the conduct of the
pharmacokinetics study. In addition, we acknowledge Laura Bollinger and
Jiro Wada at the IRF for technical writing services and figure
preparation, respectively, for this manuscript.
NR 34
TC 0
Z9 0
U1 6
U2 6
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD NOV 30
PY 2016
VL 11
IS 11
AR e0166318
DI 10.1371/journal.pone.0166318
PG 19
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EE3FV
UT WOS:000389474100019
PM 27902714
ER
PT J
AU Noh, JW
Kwon, YD
Park, J
Oh, IH
Kim, J
AF Noh, Jin-Won
Kwon, Young Dae
Park, Jumin
Oh, In-Hwan
Kim, Jinseok
TI Relationship between Physical Disability and Depression by Gender: A
Panel Regression Model
SO PLOS ONE
LA English
DT Article
ID LATE-LIFE; FUNCTIONAL DISABILITY; CHRONIC STRESS; RISK-FACTORS;
PREVALENCE; SYMPTOMS; ANXIETY; ADULTS
AB Background
Depression in persons with physical disabilities may be more common than in the general population. The purpose of this study was to examine the relationship between physical disability and depression by gender among adults, using a large, nationally representative sample.
Methods
This study used data from the Korean Longitudinal Study of Aging, Wave one through four, and ran a series of random effect panel regression models to test the relationship between physical disability status and depression by gender. We tested the moderating effect of gender on the relationship between disability status and depression level by examining the significance of the cross-product term between disability status and gender.
Results
After controlling for self-rated health, marital status, employment status, education, and age, subjects who were female or diagnosed as having any disability presented higher levels of depression scores. Further, the difference in terms of their depression level measured by Center for Epidemiologic Studies Short Depression Scale (CES-D 10) scores between those who were diagnosed as having any disability and those who were not was greater for females than for their male counterparts.
Conclusion
This study reaffirmed that disability is the risk factor of depression, using longitudinal data. In addition, female gender is the effect modifier rather than the risk factor. The effect of gender in the non-disability group, mostly composed of older persons, is limited. On the contrary, the female disability group showed more depressive symptoms than the male disability group. The gender difference in the disability group and the role of culture on these differences need further research.
C1 [Noh, Jin-Won] Eulji Univ, Dept Healthcare Management, Seongnam, South Korea.
[Noh, Jin-Won] Univ Groningen, Univ Med Ctr Groningen, Dept Hlth Sci, Global Hlth Unit, Groningen, Netherlands.
[Kwon, Young Dae] Catholic Univ Korea, Coll Med, Dept Humanities & Social Med, Seoul, South Korea.
[Kwon, Young Dae] Catholic Univ Korea, Catholic Inst Healthcare Management, Seoul, South Korea.
[Park, Jumin] NIH, Ctr Clin, Bethesda, MD 20892 USA.
[Oh, In-Hwan] Kyung Hee Univ, Sch Med, Dept Prevent Med, Seoul, South Korea.
[Kim, Jinseok] Seoul Womens Univ, Dept Social Welf, Seoul, South Korea.
RP Kim, J (reprint author), Seoul Womens Univ, Dept Social Welf, Seoul, South Korea.
EM jskim@swu.ac.kr
OI Kwon, Young Dae/0000-0002-8781-6832
FU Seoul Women's University
FX This work was supported by a research grant from Seoul Women's
University (2016).; This work was supported by a research grant from
Seoul Women's University (2016).
NR 31
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U1 0
U2 0
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD NOV 30
PY 2016
VL 11
IS 11
AR e0166238
DI 10.1371/journal.pone.0166238
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EE3FV
UT WOS:000389474100015
PM 27902709
ER
PT J
AU Ribeiro, TA
Prates, KV
Pavanello, A
Malta, A
Tofolo, LP
Martins, IP
de Oliveira, JC
Miranda, RA
Gomes, RM
Vieira, E
Franco, CCD
Barella, LF
Francisco, FA
Alves, VS
Silveira, SD
Moreira, VM
Fabricio, GS
Palma-Rigo, K
Sloboda, DM
Mathias, PCD
AF Ribeiro, Tatiane Aparecida
Prates, Kelly Valerio
Pavanello, Audrei
Malta, Ananda
Tofolo, Laize Peron
Martins, Isabela Peixoto
de Oliveira, Julio Cezar
Miranda, Rosiane Aparecida
Gomes, Rodrigo Mello
Vieira, Elaine
da Silva Franco, Claudineia Conationi
Barella, Luiz Felipe
Francisco, Flavio Andrade
Alves, Vander Silva
Silveira, Sandra da Silva
Moreira, Veridiana Mota
Fabricio, Gabriel Sergio
Palma-Rigo, Kesia
Sloboda, Deborah M.
de Freitas Mathias, Paulo Cezar
TI Acephate exposure during a perinatal life program to type 2 diabetes
SO TOXICOLOGY
LA English
DT Review
DE Acephate; Pregnancy; Lactation; Glucose metabolism; Lipid metabolism;
Offspring
ID NERVOUS-SYSTEM; ORGANOPHOSPHATE INSECTICIDES; PESTICIDE-RESIDUES;
RISK-ASSESSMENT; GROWTH; GLUCOSE; OBESITY; RATS; INSULIN; DISEASE
AB Acephate has been used extensively as an insecticide in agriculture. Its downstream sequelae are associated with hyperglycemia, lipid metabolism dysfunction, DNA damage, and cancer, which are rapidly growing epidemics and which lead to increased morbidity and mortality rates and soaring healthcare costs. Developing interventions will require a comprehensive understanding of which excess insecticides during perinatal life can cause insulin resistance and type 2 diabetes. A Wistar rat animal model suggests that acephate exposure during pregnancy and lactation causes alterations in maternal glucose metabolism and programs the offspring to be susceptible to type 2 diabetes at adulthood. Therapeutic approaches based on preventive actions to food contaminated with insecticides during pregnancy and lactation could prevent new cases of type 2 diabetes. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
C1 [Ribeiro, Tatiane Aparecida; Prates, Kelly Valerio; Pavanello, Audrei; Malta, Ananda; Tofolo, Laize Peron; Martins, Isabela Peixoto; Vieira, Elaine; da Silva Franco, Claudineia Conationi; Francisco, Flavio Andrade; Alves, Vander Silva; Silveira, Sandra da Silva; Moreira, Veridiana Mota; Palma-Rigo, Kesia; de Freitas Mathias, Paulo Cezar] State Univ Maringa 5790, Dept Biotechnol Genet & Cell Biol, Lab Secret Cell Biol, BR-87020900 Maringa, PR, Brazil.
[Sloboda, Deborah M.] MacMaster Univ, Dept Biochem & Biomed Sci Ob Gyn & Pediat, Hamilton, ON 8S 4L8, Canada.
[Barella, Luiz Felipe] Natl Inst Diabet & Digest & Kidney Dis, Mol Signalling Sect, Bioorgan Chem Lab, Natl Inst Hlth, Bethesda, MD 20892 USA.
[Miranda, Rosiane Aparecida] Univ Fed Rio de Janeiro, Carlos Chagas Filho Biophysis Inst, Mol Endocrinol Lab, BR-21941902 Rio De Janeiro, RJ, Brazil.
[de Freitas Mathias, Paulo Cezar] UPSP EGEAL Inst Polytech LaSalle Beauvais, BP 30313, F-60026 Beauvais, France.
[de Oliveira, Julio Cezar] Univ Fed Mato Grosso, Inst Hlth Sci, BR-78557267 Sinop, MT, Brazil.
[Fabricio, Gabriel Sergio] Univ Lille, CNRS, UMR 8576, Unite Glycobiol Struct & Fonctionnelle,UGSF, F-59000 Lille, France.
[Gomes, Rodrigo Mello] Univ Fed Goias, Dept Physiol Sci, Lab Neurosci & Cardiovasc Physiol, BR-74690900 Goiania, Go, Brazil.
RP Ribeiro, TA (reprint author), Univ Estadual Maringa, Dept Biotechnol Genet & Cell Biol, Block H67,Room 19,UEM Colombo Ave 5790, BR-87020900 Maringa, PR, Brazil.
EM tatianeribeiro2@hotmail.com
RI Barella, Luiz/C-1181-2014
OI Barella, Luiz/0000-0003-2211-3842
FU Brazilian Federal Foundation, Conselho National de Desenvolvimento
Cientifico e Tecnologico (CNPq); Coordenacao de Aperfeicoamento de
Pessoal de Nivel Superior (CAPES); Parana Science Foundation (Fundacao
Araucaria)
FX This work was supported by the Brazilian Federal Foundation, Conselho
National de Desenvolvimento Cientifico e Tecnologico (CNPq), Coordenacao
de Aperfeicoamento de Pessoal de Nivel Superior (CAPES), and the Parana
Science Foundation (Fundacao Araucaria).
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PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0300-483X
J9 TOXICOLOGY
JI Toxicology
PD NOV 30
PY 2016
VL 372
BP 12
EP 21
DI 10.1016/j.tox.2016.10.010
PG 10
WC Pharmacology & Pharmacy; Toxicology
SC Pharmacology & Pharmacy; Toxicology
GA EE6NY
UT WOS:000389730700002
PM 27765684
ER
PT J
AU White, SF
Tyler, P
Botkin, ML
Erway, AK
Thornton, LC
Kolli, V
Pope, K
Meffert, H
Blair, J
AF White, Stuart F.
Tyler, Patrick
Botkin, Mary L.
Erway, Anna K.
Thornton, Laura C.
Kolli, Venkata
Pope, Kayla
Meffert, Harma
Blair, James
TI Youth with substance abuse histories exhibit dysfunctional
representation of expected value during a passive avoidance task
SO PSYCHIATRY RESEARCH-NEUROIMAGING
LA English
DT Article
DE Substance abuse; Decision-making; Expected value; Prediction error
ID VENTROMEDIAL PREFRONTAL CORTEX; DISRUPTIVE BEHAVIOR DISORDERS; REWARD
PREDICTION ERRORS; DECISION-MAKING; DEPENDENT INDIVIDUALS; RESPONSE
REVERSAL; NEURAL BASIS; HUMAN BRAIN; ADDICTION; FUTURE
AB Individuals with substance abuse (SA) histories show impairment in the computations necessary for decision making, including expected value (EV) and prediction error (PE). Neuroimaging findings, however, have been inconsistent. Sixteen youth with (SA(positive)) and 29 youth without (SA(negative)) substance abuse histories completed a passive avoidance task while undergoing functional MRI. The groups did not significantly differ on age, gender composition or IQ. Behavioral results indicated that SA(positive) youth showed significantly less learning than SA(negative) youth over the task. SA(positive) youth show problems representing EV information when attempting to avoid sub-optimal choices in bilateral inferior frontal gyrus and striatum. Furthermore, SA(positive) youth showed a significantly increased differential response to reward versus punishment feedback modulated by PE in posterior cingulate cortex relative to SA(negative) youth. Disrupted decision-making is likely to exacerbate SA as a failure to represent EV during the avoidance of sub-optimal choices is likely to increase the likelihood of SA. With respect to the representation of PE, future work will be needed to clarify the impact of different substances on the neural systems underpinning PE representation. Moreover, interaction of age/development and substance abuse on PE signaling will need to be explored.
C1 [White, Stuart F.; Tyler, Patrick; Botkin, Mary L.; Erway, Anna K.; Thornton, Laura C.; Pope, Kayla; Meffert, Harma] Boys Town Natl Res Hosp, Ctr Neurobehav Res, 14100 Crawford St, Boys Town, NE 68010 USA.
[Kolli, Venkata] Creighton Univ, Sch Med, Univ Nebraska Med Ctr, Dept Psychiat, 3528 Dodge St, Omaha, NE 68131 USA.
[Blair, James] NIMH, Sect Affect Cognit Neurosci, NIH, 15K North Dr,Rm 206,MSC 2670, Bethesda, MD 20814 USA.
RP White, SF (reprint author), Boys Town Natl Res Hosp, Ctr Neurobehav Res, 14100 Crawford St, Boys Town, NE 68010 USA.
EM stuart.white@boystown.org; patrick.tyler@boystown.org;
lormarm@boystown.org; anna.erway@boystown.org;
laura.thornton@boystown.org; venkatakolli@creighton.edu;
kayla.pope@boystown.org; harma.meffert@boystown.org;
jamesblair@mail.nih.gov
OI Meffert, Harma/0000-0002-7298-7276
FU Intramural Research Program of the National Institute of Mental Health,
National Institutes of Health [1-ZIA-MH002860]
FX This work was supported by the Intramural Research Program of the
National Institute of Mental Health, National Institutes of Health
(1-ZIA-MH002860), Dr. Blair principle investigator. Drs. White and Blair
had full access to the data and take responsibility for the integrity of
the data and the accuracy of the data analysis. The authors would like
to acknowledge the contributions of Ron Copsey and Kim VanHorn to the
collection of this data. The authors would like to thank all subjects
and their families for participating.
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PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0925-4927
EI 1872-7506
J9 PSYCHIAT RES-NEUROIM
JI Psychiatry Res. Neuroimaging
PD NOV 30
PY 2016
VL 257
BP 17
EP 24
DI 10.1016/j.pscychresns.2016.08.010
PG 8
WC Clinical Neurology; Neuroimaging; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA ED8BI
UT WOS:000389096500004
PM 27716545
ER
PT J
AU Patel, DP
Nair, S
Suhagia, BN
Patel, BM
AF Patel, Daxesh P.
Nair, Sneha
Suhagia, Bhanubhai N.
Patel, Bhargav M.
TI A novel, sensitive and selective method of UPLC/MS-MS for rapid
simultaneous determination of midodrine and its active metabolite
desglymidodrine in human plasma: Application to support bioequivalence
study in healthy human volunteers
SO JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
LA English
DT Article
DE Midodrine; Desglymidodrine; UPLC-MS/MS; Sensitive; High throughput;
Incurred sample reanalysis
ID PERFORMANCE LIQUID-CHROMATOGRAPHY; PRODRUG MIDODRINE; QUANTIFICATION;
DEGLYMIDODRINE; PRESSURE; THERAPY; SYNCOPE; MS/MS; HPLC
AB A specific, rapid, sensitive and selective ultra-performance liquid chromatography - tandem mass spectrometry has been developed for the simultaneous determination of midodrine and desglymidodrine in human plasma. The analytes and its deuterated analogs were quantitatively extracted from 100 mu L of human plasma by solid phase extraction technique. Separation of analytes was achieved on the Waters Acquity UPLC BEH C18 (50 x 2.1 mm, 1.7 mu m) column using acetonittile-4.0 mM ammonium formate, pH 2.5(90:10, v/v) as mobile phase. The protonated analytes were quantified by selected reaction monitoring in the positive ionization mode by triple quadrupole mass spectrometer. The calibration plots were linear over the concentration range of 0.050-50.0 ngiml.. The intra-batch and inter-batch precision (%CV) across quality control levels was <4.0 and the% mean relative recovery was >= 96%. Various other parameters like stability in different conditions; matrix effect and reproducibility of the method were performed in accordance with the guidelines specified by the USFDA for bioanalytical method development and validation. The developed method was successfully administered to the pharmacokinetics study of 5 mg midodrine tablet in 12 healthy subjects. Reproducibility of assay was proved by reanalysis of 48 incurred samples. (C) 2016 Elsevier B.V. All rights reserved.
C1 [Patel, Daxesh P.] NCI, Lab Metab, Ctr Canc Res, Bethesda, MD 20892 USA.
[Nair, Sneha] Gujarat Univ, Sch Sci, Dept Chem, Ahmadabad 380009, Gujarat, India.
[Suhagia, Bhanubhai N.] Dharamsinh Desai Univ, Nadiad, Gujarat, India.
[Patel, Bhargav M.] St Xaviers Coll, Dept Chem, Ahmadabad 380009, Gujarat, India.
RP Patel, BM (reprint author), St Xaviers Coll, Dept Chem, Ahmadabad 380009, Gujarat, India.
EM bhargavp1001@gmail.com
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PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0731-7085
EI 1873-264X
J9 J PHARMACEUT BIOMED
JI J. Pharm. Biomed. Anal.
PD NOV 30
PY 2016
VL 131
BP 355
EP 363
DI 10.1016/j.jpba.2016.09.005
PG 9
WC Chemistry, Analytical; Pharmacology & Pharmacy
SC Chemistry; Pharmacology & Pharmacy
GA EB8GB
UT WOS:000387628400046
PM 27639073
ER
PT J
AU Liu, MT
Wang, JN
Liu, P
AF Liu, Mingtao
Wang, Jennie
Liu, Paul
TI HPLC method development, validation, and impurity characterization of a
potent antitumor nucleoside, T-dCyd (NSC 764276)
SO JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
LA English
DT Article
DE 4 '-thio-2 '-deoxycytidine; T-dCyd; NSC 764276; Forced degradation; HPLC
validation; Impurity and degradation product characterization
ID DNA METHYLTRANSFERASE INHIBITOR; HISTONE DEACETYLATION; BREAST-CANCER;
METHYLATION; CELLS; 5-FLUORO-2'-DEOXYCYTIDINE; DEGRADATION; METABOLITES;
ZEBULARINE; MECHANISM
AB An HPLC method for the assay of an anticancer nucleoside, 4'-thio-2'-deoxycytidine (T-dCyd, NSC 764276), has been developed and validated. The stress testing of T-dCyd was carried out in accordance with ICH guidelines Q1A (R2) under acidic, alkaline, oxidative, thermolytic, and photolytic conditions. The separation of T-dCyd from its impurities and degradation products was achieved in 40 min on a Luna (R) Phenyl-Hexyl column (150 mm x 4.6 mm i.d., 3 mu m) with a gradient elution using ammonium phosphate buffer (pH 3.85) and methanol as the mobile phase. The gradient starts from 2% and ends at 80% of methanol. Detection is by UV at 282 nm. LC-QTOF/MS was used to obtain mass data for characterization of impurities and degradation products. The proposed HPLC assay method was validated for specificity, linearity (concentration range 025-0.75 mg/mL, r >= 0.9998), accuracy (recovery 98.1-102.0%), precision (RSD <= 1.5%), and sensitivity (LOD 0.1 mu g/mL). The developed method was suitable for the quality control and stability monitoring of the T-dCyd drug substance. (C) 2016 Elsevier B.V. All rights reserved.d
C1 [Liu, Mingtao; Wang, Jennie] SRI Int, 333 Ravenswood Ave, Menlo Pk, CA 94025 USA.
[Liu, Paul] NCI, DCTD, Pharmaceut Resources Branch, 9609 Med Ctr Dr, Bethesda, MD 20892 USA.
RP Wang, JN (reprint author), SRI Int, 333 Ravenswood Ave, Menlo Pk, CA 94025 USA.; Liu, P (reprint author), NCI, DCTD, Pharmaceut Resources Branch, 9609 Med Ctr Dr, Bethesda, MD 20892 USA.
EM jennie.wang@sri.com; liup@dtpepn.nci.nih.gov
FU National Cancer Institute, National Institutes of Health
[HHSN261201200028C]
FX This work was funded in whole or in part by Federal funds from the
National Cancer Institute, National Institutes of Health, under Contract
No. HHSN261201200028C. 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.
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PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0731-7085
EI 1873-264X
J9 J PHARMACEUT BIOMED
JI J. Pharm. Biomed. Anal.
PD NOV 30
PY 2016
VL 131
BP 429
EP 435
DI 10.1016/j.jpba.2016.08.034
PG 7
WC Chemistry, Analytical; Pharmacology & Pharmacy
SC Chemistry; Pharmacology & Pharmacy
GA EB8GB
UT WOS:000387628400054
PM 27661436
ER
PT J
AU Ji, J
Qin, YF
Wang, R
Huang, ZY
Zhang, Y
Zhou, R
Song, L
Ling, XF
Hu, ZB
Miao, DS
Shen, HB
Xia, YK
Wang, XR
Lu, CC
AF Ji, Juan
Qin, Yufeng
Wang, Rong
Huang, Zhenyao
Zhang, Yan
Zhou, Ran
Song, Ling
Ling, Xiufeng
Hu, Zhibin
Miao, Dengshun
Shen, Hongbing
Xia, Yankai
Wang, Xinru
Lu, Chuncheng
TI Copy number gain of VCX, X-linked multi-copy gene, leads to cell
proliferation and apoptosis during spermatogenesis
SO ONCOTARGET
LA English
DT Article
DE copy number variations; non-obstructive azoospermia
ID SEX-CHROMOSOME INACTIVATION; MALE-INFERTILITY; NONOBSTRUCTIVE
AZOOSPERMIA; Y-CHROMOSOME; CANCER/TESTIS ANTIGENS; GERM-CELLS;
MALE-MICE; VARIANTS; MUTATIONS; FAILURE
AB Male factor infertility affects one-sixth of couples worldwide, and non-obstructive azoospermia (NOA) is one of the most severe forms. In recent years there has been increasing evidence to implicate the participation of X chromosome in the process of spermatogenesis. To uncover the roles of X-linked multi-copy genes in spermatogenesis, we performed systematic analysis of X-linked gene copy number variations (CNVs) and Y chromosome haplogrouping in 447 idiopathic NOA patients and 485 healthy controls. Interestingly, the frequency of individuals with abnormal level copy of Variable charge, X-linked (VCX) was significantly different between cases and controls after multiple test correction (p = 5.10 x 10(-5)). To discriminate the effect of gain/loss copies in these genes, we analyzed the frequency of X-linked multi-copy genes in subjects among subdivided groups. Our results demonstrated that individuals with increased copy numbers of Nuclear RNA export factor 2 (NXF2) (p = 9.21 x 10(-8)) and VCX (p = 1.97 x 10(-4)) conferred the risk of NOA. In vitro analysis demonstrated that increasing copy number of VCX could upregulate the gene expression and regulate cell proliferation and apoptosis. Our study establishes a robust association between the VCX CNVs and NOA risk.
C1 [Ji, Juan; Huang, Zhenyao; Zhang, Yan; Zhou, Ran; Song, Ling; Hu, Zhibin; Miao, Dengshun; Shen, Hongbing; Xia, Yankai; Wang, Xinru; Lu, Chuncheng] Nanjing Med Univ, Inst Toxicol, State Key Lab Reprod Med, Nanjing, Jiangsu, Peoples R China.
[Ji, Juan; Huang, Zhenyao; Zhang, Yan; Zhou, Ran; Song, Ling; Xia, Yankai; Wang, Xinru; Lu, Chuncheng] Nanjing Med Univ, Sch Publ Hlth, Minist Educ, Key Lab Modern Toxicol, Nanjing, Jiangsu, Peoples R China.
[Qin, Yufeng] Natl Inst Environm Hlth Sci, Epigenet & Stem Cell Biol Lab, Res Triangle Pk, NC USA.
[Ji, Juan; Ling, Xiufeng] Nanjing Med Univ, Nanjing Matern & Child Hlth Care Hosp, Dept Children Hlth Care, Nanjing, Jiangsu, Peoples R China.
[Wang, Rong; Miao, Dengshun] Nanjing Med Univ, Dept Anat Histol & Embryol, Res Ctr Bone & Stem Cells, Nanjing, Jiangsu, Peoples R China.
[Hu, Zhibin; Shen, Hongbing] Nanjing Med Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Nanjing, Jiangsu, Peoples R China.
[Hu, Zhibin; Shen, Hongbing] Nanjing Med Univ, Sch Publ Hlth, Minist Educ, Key Lab Modern Toxicol, Nanjing, Jiangsu, Peoples R China.
RP Lu, CC (reprint author), Nanjing Med Univ, Inst Toxicol, State Key Lab Reprod Med, Nanjing, Jiangsu, Peoples R China.; Lu, CC (reprint author), Nanjing Med Univ, Sch Publ Hlth, Minist Educ, Key Lab Modern Toxicol, Nanjing, Jiangsu, Peoples R China.
EM chunchenglu@njmu.edu.cn
FU National Natural Science Foundation of China [81471500, 81671461,
81322039]; Priority Academic Program for the Development of Jiangsu
Higher Education Institutions (Public Health and Preventive Medicine);
[BK20130041]
FX We thank all the research staff and students who took part in this work.
Funding was provided by grants from the National Natural Science
Foundation of China (81471500, 81671461 and 81322039), Distinguished
Young Scholars of Jiangsu Province (BK20130041) and the Priority
Academic Program for the Development of Jiangsu Higher Education
Institutions (Public Health and Preventive Medicine).
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PU IMPACT JOURNALS LLC
PI ALBANY
PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA
SN 1949-2553
J9 ONCOTARGET
JI Oncotarget
PD NOV 29
PY 2016
VL 7
IS 48
BP 78532
EP 78540
DI 10.18632/oncotarget.12397
PG 9
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA EE5HH
UT WOS:000389636000028
PM 27705943
ER
PT J
AU Lewis, MJ
Liu, JZ
Libby, EF
Lee, M
Crawford, NPS
Hurst, DR
AF Lewis, Monica J.
Liu, Jianzhong
Libby, Emily Falk
Lee, Minnkyong
Crawford, Nigel P. S.
Hurst, Douglas R.
TI SIN3A and SIN3B differentially regulate breast cancer metastasis
SO ONCOTARGET
LA English
DT Article
DE SIN3A; SIN3B; breast cancer; invasion; metastasis
ID CHROMATIN REMODELING COMPLEXES; GENE-EXPRESSION; RNA-SEQ; MDA-MB-435
CELLS; COREPRESSOR; SURVIVAL; SUPPRESSION; PROGRESSION; BIOLOGY; PROTEIN
AB SIN3 corepressor complexes play important roles in both normal development and breast cancer. Mammalian cells have two paralogs of SIN3 (SIN3A and SIN3B) that are encoded by distinct genes and have unique functions in many developmental processes. However, specific roles for SIN3A and SIN3B in breast cancer progression have not been characterized. We generated stable knockdown cells of SIN3 paralogs individually and in combination using three non-overlapping shRNA. Stable knockdown of SIN3B caused a significant decrease in transwell invasion through Matrigel and decreased the number of invasive colonies when grown in a 3D extracellular matrix. Conversely, stable knockdown of SIN3A significantly increased transwell invasion and increased the number of invasive colonies. These results were corroborated in vivo in which SIN3B knockdown significantly decreased and SIN3A knockdown increased experimental lung metastases. RNA sequencing was used to identify unique targets and biological pathways that were altered upon knockdown of SIN3A compared to SIN3B. Additionally, we analyzed microarray data sets to identify correlations of SIN3A and SIN3B expression with survival in patients with breast cancer. These data sets indicated that high mRNA expression of SIN3A as well as low mRNA expression of SIN3B correlates with longer relapse free survival specifically in patients with triple negative breast cancer which corresponds with our in vitro and in vivo data. These results demonstrate key functional differences between SIN3 paralogs in regulating the process of breast cancer metastasis and suggest metastasis suppressive roles of SIN3A and metastasis promoting roles of SIN3B.
C1 [Lewis, Monica J.; Liu, Jianzhong; Libby, Emily Falk; Hurst, Douglas R.] Univ Alabama Birmingham, Dept Pathol, Birmingham, AL 35294 USA.
[Lee, Minnkyong; Crawford, Nigel P. S.] NHGRI, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA.
RP Hurst, DR (reprint author), Univ Alabama Birmingham, Dept Pathol, Birmingham, AL 35294 USA.
EM dhurst@uab.edu
OI Hurst, Douglas/0000-0002-1296-2210
FU American Cancer Society [RSG-11-259-01-CSM]; METAvivor Research and
Support, Inc; Cancer Prevention and Control Training Program of the
University of Alabama at Birmingham [R25 CA047888]
FX This study was funded in part by the American Cancer Society
RSG-11-259-01-CSM (DRH), METAvivor Research and Support, Inc (DRH) and
the Cancer Prevention and Control Training Program of the University of
Alabama at Birmingham R25 CA047888 (EFL).
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PU IMPACT JOURNALS LLC
PI ORCHARD PARK
PA 6666 E QUAKER ST, STE 1, ORCHARD PARK, NY 14127 USA
SN 1949-2553
J9 ONCOTARGET
JI Oncotarget
PD NOV 29
PY 2016
VL 7
IS 48
BP 78713
EP 78725
DI 10.18632/oncotarget.12805
PG 13
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA EE5HH
UT WOS:000389636000043
PM 27780928
ER
PT J
AU Harada, T
Nakamura, Y
Sato, K
Nagaya, T
Okuyama, S
Ogata, F
Choyke, PL
Kobayashi, H
AF Harada, Toshiko
Nakamura, Yuko
Sato, Kazuhide
Nagaya, Tadanobu
Okuyama, Shuhei
Ogata, Fusa
Choyke, Peter L.
Kobayashi, Hisataka
TI Near-infrared photoimmunotherapy with galactosyl serum albumin in a
model of diffuse peritoneal disseminated ovarian cancer
SO ONCOTARGET
LA English
DT Article
DE near-infrared photoimmunotherapy; ovarian cancer; peritoneal cancer
metastases; galactosyl serum albumin; beta-D-galactose receptor
ID GYNECOLOGIC-ONCOLOGY-GROUP; IN-VIVO; MONOCLONAL-ANTIBODIES; FLUORESCENT
PROTEINS; TUMOR; AVIDIN; ANTIGEN; CHASE
AB Near-infrared photoimmunotherapy (NIR-PIT) is a highly cell-selective cancer therapy based on an armed antibody conjugated with a phthalocyanine-based photo-absorber, IRDye700DX (IR700). NIR-PIT can quickly kill target cells that express specific proteins on the cellular membrane but only when the antibody-IR700 conjugate binds to the cell membrane and is then exposed to NIR light. NIR-PIT is highly selective based on the specificity of the antibody. Galactosyl serum albumin (GSA) is composed of albumin decorated with galactose molecules conjugated to the carboxyl groups of albumin. GSA binds to beta-D-galactose receptors, a surface lectin, which are overexpressed on the cell surface of many cancers, including ovarian cancers and is quickly internalized after binding. Here, we demonstrate the feasibility of NIR-PIT in a model of disseminated peritoneal ovarian cancer (SHIN3 cells) using GSA-IR700 that binds to beta-D-galactose receptors. GSA-IR700 bound quickly to SHIN3 cells, then accumulated in the endo-lysosomes. Cell-specific killing was observed in vitro, yet a relatively large dose of NIR light exposure was required for cell killing compared to antibody-IR700 conjugates. To evaluate in vivo therapeutic effects of GSA-IR700 NIR-PIT, peritoneal disseminated SHIN3 tumor-bearing mice were separated into four groups: no treatment; NIR light only; GSA-IR700 only; and GSA-IR700 NIR-PIT. Repeated NIR-PIT showed significant suppression of tumor based on bioluminescence compared to the other groups (p < 0.05). Thus, repeated NIR-PIT using GSA-IR700 can achieve efficient antitumor effects, although GSA-IR700 NIR-PIT was less effective than antibody-IR700 NIR-PIT conjugates likely due to the rapid internalization of GSA-IR700.
C1 [Harada, Toshiko; Nakamura, Yuko; Sato, Kazuhide; Nagaya, Tadanobu; Okuyama, Shuhei; Ogata, Fusa; Choyke, Peter L.; Kobayashi, Hisataka] NCI, Mol Imaging Program, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Kobayashi, H (reprint author), NCI, Mol Imaging Program, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM kobayash@mail.nih.gov
FU Intramural Research Program of the National Institute of Health,
National Cancer Institute, Center for Cancer Research [ZIA-BC011513]
FX This research was supported by the Intramural Research Program of the
National Institute of Health, National Cancer Institute, Center for
Cancer Research. (ZIA-BC011513).
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PU IMPACT JOURNALS LLC
PI ALBANY
PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA
SN 1949-2553
J9 ONCOTARGET
JI Oncotarget
PD NOV 29
PY 2016
VL 7
IS 48
BP 79394
EP 79402
DI 10.18632/oncotarget.12710
PG 9
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA EE5HH
UT WOS:000389636000096
ER
PT J
AU Lee, JH
Cho, HS
Lee, JJ
Jun, SY
Ahn, JH
Min, JS
Yoon, JY
Choi, MH
Jeon, SJ
Lim, JH
Jung, CR
Kim, DS
Kim, HT
Factor, VM
Lee, YH
Thorgeirsson, SS
Kim, CH
Kim, NS
AF Lee, Jae-Hye
Cho, Hyun-Soo
Lee, Jeong-Ju
Jun, Soo Young
Ahn, Jun-Ho
Min, Ju-Sik
Yoon, Ji-Yong
Choi, Min-Hyuk
Jeon, Su-Jin
Lim, Jung Hwa
Jung, Cho-Rok
Kim, Dae-Soo
Kim, Hyun-Taek
Factor, Valentina M.
Lee, Yun-Han
Thorgeirsson, Snorri S.
Kim, Cheol-Hee
Kim, Nam-Soon
TI Plasma glutamate carboxypeptidase is a negative regulator in liver
cancer metastasis
SO ONCOTARGET
LA English
DT Article
DE liver cancer; metastasis; PGCP; Wnt/beta-catenin
ID EPITHELIAL-MESENCHYMAL TRANSITION; HEPATOCELLULAR-CARCINOMA;
BETA-CATENIN; STEM-CELLS; DICKKOPF 4; TUMOR-METASTASIS; INVASION;
ACTIVATION; MIGRATION; PATHWAY
AB Tumor metastasis is the leading cause of cancer death. In the metastatic process, EMT is a unique phenotypic change that plays an important role in cell invasion and changes in cell morphology. Despite the clinical significance, the mechanism underlying tumor metastasis is still poorly understood. Here we report a novel mechanism by which secreted plasma glutamate carboxypeptidase(PGCP) negatively involves Wnt/beta-catenin signaling by DKK4 regulation in liver cancer metastasis. Pathway analysis of the RNA sequencing data showed that PGCP knockdown in liver cancer cell lines enriched the functions of cell migration, motility and mesenchymal cell differentiation. Depletion of PGCP promoted cell migration and invasion via activation of Wnt/beta-catenin signaling pathway components such as phospho-LRP6 and beta-catenin. Also, addition of DKK4 antagonized the Wnt/beta-catenin signaling cascade in a thyroxine (T4)-dependent manner. In an in vivo study, metastatic nodules were observed in the lungs of the mice after injection of shPGCP stable cell lines. Our findings suggest that PGCP negatively associates with Wnt/beta-catenin signaling during metastasis. Targeting this regulation may represent a novel and effective therapeutic option for liver cancer by preventing metastatic activity of primary tumor cells.
C1 [Lee, Jae-Hye; Cho, Hyun-Soo; Lee, Jeong-Ju; Jun, Soo Young; Ahn, Jun-Ho; Min, Ju-Sik; Yoon, Ji-Yong; Choi, Min-Hyuk; Jeon, Su-Jin; Kim, Dae-Soo; Kim, Nam-Soon] Korea Res Inst Biosci & Biotechnol, Genome Res Ctr, Daejeon 305333, South Korea.
[Lim, Jung Hwa; Jung, Cho-Rok] Korea Res Inst Biosci & Biotechnol, Gene Therapy Res Unit, Daejeon 305333, South Korea.
[Lee, Jae-Hye; Cho, Hyun-Soo; Jun, Soo Young; Choi, Min-Hyuk; Jeon, Su-Jin; Kim, Dae-Soo; Kim, Nam-Soon] Korea Univ Sci & Technol, Dept Funct Genom, Daejeon 305333, South Korea.
[Kim, Hyun-Taek; Kim, Cheol-Hee] Chungnam Natl Univ, Dept Biol, Daejeon 305764, South Korea.
[Factor, Valentina M.] NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Lee, Yun-Han] Keimyung Univ, Dept Mol Med, Sch Med, Daegu 704701, South Korea.
[Thorgeirsson, Snorri S.] NCI, Human Carcinogenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Kim, NS (reprint author), Korea Res Inst Biosci & Biotechnol, Genome Res Ctr, Daejeon 305333, South Korea.; Kim, NS (reprint author), Korea Univ Sci & Technol, Dept Funct Genom, Daejeon 305333, South Korea.
EM nskim37@kribb.re.kr
FU Basic Science Research Program of the National Research Foundation of
Korea (NRF) - Ministry of Education, Science and Technology
[NRF-2014M3A9A5034157, 2013R1A2A2A01067556, 2014M3C9A2064619,
2014R1A2A1A110 53562]; KRIBB Research Initiative Program
FX The PGCP clone was provided by the Korea Human Gene Bank, KRIBB, KOREA.
Supported by the Basic Science Research Program of the National Research
Foundation of Korea (NRF) funded by the Ministry of Education, Science
and Technology (NRF-2014M3A9A5034157, 2013R1A2A2A01067556,
2014M3C9A2064619, 2014R1A2A1A110 53562), and by the KRIBB Research
Initiative Program.
NR 42
TC 0
Z9 0
U1 1
U2 1
PU IMPACT JOURNALS LLC
PI ALBANY
PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA
SN 1949-2553
J9 ONCOTARGET
JI Oncotarget
PD NOV 29
PY 2016
VL 7
IS 48
BP 79760
EP 79772
DI 10.18632/oncotarget.12967
PG 13
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA EE5HH
UT WOS:000389636000124
ER
PT J
AU Chowella, G
Viboud, C
AF Chowella, Gerardo
Viboud, Cecile
TI Pandemic influenza and socioeconomic disparities: Lessons from 1918
Chicago
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Editorial Material
ID MORTALITY PATTERNS; WAVE
C1 [Chowella, Gerardo] Georgia State Univ, Sch Publ Hlth, Div Epidemiol & Biostat, Atlanta, GA 30302 USA.
[Chowella, Gerardo; Viboud, Cecile] NIH, Div Int Epidemiol & Populat Studies, Fogarty Int Ctr, Bldg 10, Bethesda, MD 20892 USA.
RP Chowella, G (reprint author), Georgia State Univ, Sch Publ Hlth, Div Epidemiol & Biostat, Atlanta, GA 30302 USA.; Chowella, G (reprint author), NIH, Div Int Epidemiol & Populat Studies, Fogarty Int Ctr, Bldg 10, Bethesda, MD 20892 USA.
EM gchowell@gsu.edu
NR 20
TC 0
Z9 0
U1 0
U2 0
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD NOV 29
PY 2016
VL 113
IS 48
BP 13557
EP 13559
DI 10.1073/pnas.1616537113
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA ED4QR
UT WOS:000388835700035
PM 27911763
ER
PT J
AU Yu, GC
Cook, TR
Li, Y
Yan, XZ
Wu, D
Shao, L
Shen, J
Tang, GP
Huang, FH
Chen, XY
Stang, PJ
AF Yu, Guocan
Cook, Timothy R.
Li, Yang
Yan, Xuzhou
Wu, Dan
Shao, Li
Shen, Jie
Tang, Guping
Huang, Feihe
Chen, Xiaoyuan
Stang, Peter J.
TI Tetraphenylethene-based highly emissive metallacage as a component of
theranostic supramolecular nanoparticles
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE supramolecular coordination complex; self-assembly; discrete
metallacage; theranostic; drug delivery
ID DRUG-DELIVERY; BIOMEDICAL APPLICATIONS; CANCER-THERAPY; PLATINUM;
FUNCTIONALIZATION; THERAPEUTICS; NANOCARRIERS; SELECTIVITY; POLYMERS;
PLATFORM
AB A theranostic agent combines diagnostic reporter with therapeutic activity in a single entity, an approach that seeks to increase the efficacy of cancer treatment. Herein, we describe the synthesis of a highly emissive tetraphenylethene-based metallacage using multicomponent coordination-driven self-assembly that exhibits a coordination-triggered aggregation-induced emission (AIE) enhancement. The formation of metallacage-loaded nanoparticles (MNPs) occurs when the assembly is treated with two variants of a 1,2-distearoyl-phosphatidylethanolamine (DSPE)/polyethylene glycol (PEG) conjugate, mPEG-DSPE, and biotin-PEG-DSPE. This combination endows the resultant MNPs with excellent stability and targeting ability, specifically enabling selective delivery of the metallacages to cancer cells that overexpress biotin receptors via receptor-mediated endocytosis. Although the mechanism of activity is based on existing Pt(II) anticancer drugs such as oxaliplatin, carboplatin, and cisplatin, in vitro and in vivo studies indicate that the MNPs are more active and show low systemic activity while also possessing emissive properties that allow for fluorescence-based imaging. This pioneering example of a metallacage that combines biologically active components with AIE imaging establishes supra-molecular coordination complexes imbedded within nanoparticles as a promising potential theranostic platform for cancer treatment.
C1 [Yu, Guocan; Shao, Li; Huang, Feihe] Zhejiang Univ, State Key Lab Chem Engn, Ctr Chem High Performance & Novel Mat, Dept Chem, Hangzhou 310027, Peoples R China.
[Cook, Timothy R.] SUNY Buffalo, Dept Chem, 359 Nat Sci Complex, Buffalo, NY 14260 USA.
[Li, Yang; Wu, Dan; Shen, Jie; Tang, Guping] Zhejiang Univ, Dept Chem, Inst Chem Biol & Pharmaceut Chem, Hangzhou 310027, Peoples R China.
[Yan, Xuzhou; Stang, Peter J.] Univ Utah, Dept Chem, Salt Lake City, UT 84112 USA.
[Chen, Xiaoyuan] Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD 20892 USA.
RP Huang, FH (reprint author), Zhejiang Univ, State Key Lab Chem Engn, Ctr Chem High Performance & Novel Mat, Dept Chem, Hangzhou 310027, Peoples R China.; Stang, PJ (reprint author), Univ Utah, Dept Chem, Salt Lake City, UT 84112 USA.; Chen, XY (reprint author), Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD 20892 USA.
EM fhuang@zju.edu.cn; shawn.chen@nih.gov; stang@chem.utah.edu
RI Huang, Feihe/A-1020-2012
OI Huang, Feihe/0000-0003-3177-6744
FU National Science Foundation [1212799]; National Basic Research Program
[2013CB834502]; National Natural Science Foundation of China [21125417,
21434005, 21620102006]; Fundamental Research Funds for the Central
Universities; Key Science Technology Innovation Team of Zhejiang
Province [2013TD02]; Open Project of State Key Laboratory of
Supramolecular Structure and Materials Grant [sklssm201509]
FX Financial support was provided by National Science Foundation Grant
1212799 (to P.J.S.); National Basic Research Program Grant 2013CB834502;
National Natural Science Foundation of China Grants 21125417, 21434005,
and 21620102006; the Fundamental Research Funds for the Central
Universities; Key Science Technology Innovation Team of Zhejiang
Province Grant 2013TD02; and Open Project of State Key Laboratory of
Supramolecular Structure and Materials Grant sklssm201509 (to F.H.).
NR 28
TC 0
Z9 0
U1 52
U2 52
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 NOV 29
PY 2016
VL 113
IS 48
BP 13720
EP 13725
DI 10.1073/pnas.1616836113
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA ED4QR
UT WOS:000388835700062
PM 27856738
ER
PT J
AU Brouwer, C
Jenko, KJ
Zoghbi, SS
Morse, CL
Innis, RB
Pike, VW
AF Brouwer, Chad
Jenko, Kimberly J.
Zoghbi, Sami S.
Morse, Cheryl L.
Innis, Robert B.
Pike, Victor W.
TI Translocator protein ligands based on
N-methyl-(quinolin-4-yl)oxypropanamides with properties suitable for PET
radioligand development
SO EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
LA English
DT Article
DE Translocator protein; PET; Carbon-11; Ligand; Binding affinity;
Lipophilic efficiency
ID POSITRON-EMISSION-TOMOGRAPHY; PERIPHERAL BENZODIAZEPINE-RECEPTOR;
ALZHEIMERS-DISEASE PATIENTS; 18 KDA; HUMAN-BRAIN; IN-VIVO;
BINDING-SITES; GENETIC-POLYMORPHISM; HEALTHY HUMANS; TSPO
AB Modifications to an N-methyl-(quinolin-4-yl)oxypropanamide scaffold were explored to discover leads for developing new radioligands for PET imaging of brain TSPO (translocator protein), a biomarker of neuroinfiammation. Whereas contraction of the quinolinyl portion of the scaffold or cyclization of the tertiary amido group abolished high TSPO affinity, insertion of an extra nitrogen atom into the 2-arylquinolinyl portion was effective in retaining sub-nanomolar affinity for rat TSPO, while also decreasing lipophilicity to within the moderate range deemed preferable for a PET radioligand. Replacement of a phenyl group on the amido nitrogen with an isopropyl group was similarly effective. Among others, compound 20 (N-methyl-N-phenyl-2-[2-(pyridin-2-yl)-1,8-naphthyridin-4-yloxy]propanamide) appears especially appealing for PET radioligand development, based on high selectivity and high affinity (K-i = 0.5 nM) for rat TSPO, moderate lipophilicity (logD = 2.48), and demonstrated amenability to labeling with carbon-11. Published by Elsevier Masson SAS.
C1 [Brouwer, Chad; Jenko, Kimberly J.; Zoghbi, Sami S.; Morse, Cheryl L.; Innis, Robert B.; Pike, Victor W.] NIMH, Mol Imaging Branch, NIH, Bldg 10,Room B3 C346A,10 Ctr Dr, Bethesda, MD 20892 USA.
RP Pike, VW (reprint author), NIMH, Mol Imaging Branch, NIH, Bldg 10,Room B3 C346A,10 Ctr Dr, Bethesda, MD 20892 USA.
EM pikev@mail.nih.gov
FU Intramural Research Program of the National Institutes of Health (NIH);
NIMH [ZIA MH0023793, ZIAMH002852]
FX This study was supported by the Intramural Research Program of the
National Institutes of Health (NIH), specifically the NIMH (projects ZIA
MH0023793 and ZIAMH002852). We thank the NIH Clinical Center PET
Department (Chief: Dr. Peter Herscovitch) for radioisotope production.
NR 51
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U1 1
U2 1
PU ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
PI PARIS
PA 23 RUE LINOIS, 75724 PARIS, FRANCE
SN 0223-5234
EI 1768-3254
J9 EUR J MED CHEM
JI Eur. J. Med. Chem.
PD NOV 29
PY 2016
VL 124
BP 677
EP 688
DI 10.1016/j.ejmech.2016.08.046
PG 12
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA ED0PO
UT WOS:000388544600053
PM 27622910
ER
PT J
AU Lui, JC
Garrison, P
Nguyen, Q
Ad, M
Keembiyehetty, C
Chen, WP
Jee, YH
Landman, E
Nilsson, O
Barnes, KM
Baron, J
AF Lui, Julian C.
Garrison, Presley
Nguyen, Quang
Ad, Michal
Keembiyehetty, Chithra
Chen, Weiping
Jee, Youn Hee
Landman, Ellie
Nilsson, Ola
Barnes, Kevin M.
Baron, Jeffrey
TI EZH1 and EZH2 promote skeletal growth by repressing inhibitors of
chondrocyte proliferation and hypertrophy
SO NATURE COMMUNICATIONS
LA English
DT Article
ID CAUSE WEAVER SYNDROME; GENE-EXPRESSION; SOTOS-SYNDROME; HUMAN HEIGHT;
LYSINE 27; MUTATIONS; OVERGROWTH; METHYLATION; H3K27; PLATE
AB Histone methyltransferases EZH1 and EZH2 catalyse the trimethylation of histone H3 at lysine 27 (H3K27), which serves as an epigenetic signal for chromatin condensation and transcriptional repression. Genome-wide associated studies have implicated EZH2 in the control of height and mutations in EZH2 cause Weaver syndrome, which includes skeletal overgrowth. Here we show that the combined loss of Ezh1 and Ezh2 in chondrocytes severely impairs skeletal growth in mice. Both of the principal processes underlying growth plate chondrogenesis, chondrocyte proliferation and hypertrophy, are compromised. The decrease in chondrocyte proliferation is due in part to derepression of cyclin-dependent kinase inhibitors Ink4a/b, while ineffective chondrocyte hypertrophy is due to the suppression of IGF signalling by the increased expression of IGF-binding proteins. Collectively, our findings reveal a critical role for H3K27 methylation in the regulation of chondrocyte proliferation and hypertrophy in the growth plate, which are the central determinants of skeletal growth.
C1 [Lui, Julian C.; Garrison, Presley; Nguyen, Quang; Ad, Michal; Jee, Youn Hee; Barnes, Kevin M.; Baron, Jeffrey] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Growth & Dev, NIH, CRC, Room 1-3330,10 Ctr Dr,MSC 1103, Bethesda, MD 20892 USA.
[Keembiyehetty, Chithra; Chen, Weiping] NIDDK, Genom Core, NIH, Bldg8,Room 1A11,8 Ctr Dr, Bethesda, MD 20892 USA.
[Landman, Ellie; Nilsson, Ola] Karolinska Inst, Div Pediat Endocrinol Q2 08, Dept Womens & Childrens Hlth, S-17176 Stockholm, Sweden.
[Landman, Ellie; Nilsson, Ola] Univ Hosp, S-17176 Stockholm, Sweden.
[Nilsson, Ola] Univ Orebro, Dept Med Sci, Rm C1213, S-70185 Orebro, Sweden.
[Nilsson, Ola] Univ Hosp, S-70185 Orebro, Sweden.
RP Lui, JC (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Growth & Dev, NIH, CRC, Room 1-3330,10 Ctr Dr,MSC 1103, Bethesda, MD 20892 USA.
EM luichunk@mail.nih.gov
RI Lui, Chun Kin Julian/E-2253-2012
FU Intramural Research Program of the Eunice Kennedy Shriver National
Institute of Child Health and Human Development, NIH; Swedish Research
Council [521-2014-3063, 2015-02227]; Swedish Governmental Agency for
Innovation Systems (Vinnova) [2014-01438]; Marianne and Marcus
Wallenberg Foundation; Stockholm County Council; Byggmastare Olle
Engkvist's Foundation; Stiftelsen Frimurare Barnhuset i Stockholm;
Karolinska Institutet
FX We thank Jeffrey Hanson from LCM core of NCI for advice and guidance of
microdissection of growth plate zones with LCM equipment. We thank Dr
Yoshiyuki Wakabayashi from DNA Sequencing and Computational Biology Core
of NHLBI for help in chromatin shearing and sonication of chondrocytes.
We thank Dr Ge Kai from NIDDK for useful advice on Ezh2. This work was
supported by the Intramural Research Program of the Eunice Kennedy
Shriver National Institute of Child Health and Human Development, NIH.
In addition, O.N. was supported by grants from the Swedish Research
Council (grant nos 521-2014-3063 and 2015-02227), the Swedish
Governmental Agency for Innovation Systems (Vinnova; 2014-01438),
Marianne and Marcus Wallenberg Foundation, the Stockholm County Council,
Byggmastare Olle Engkvist's Foundation, Stiftelsen Frimurare Barnhuset i
Stockholm and Karolinska Institutet.
NR 42
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U1 12
U2 12
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2041-1723
J9 NAT COMMUN
JI Nat. Commun.
PD NOV 29
PY 2016
VL 7
AR 13685
DI 10.1038/ncomms13685
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA ED2GN
UT WOS:000388662100001
PM 27897169
ER
PT J
AU Zhang, Q
Matsuura, K
Kleiner, DE
Zamboni, F
Alter, HJ
Farci, P
AF Zhang, Quan
Matsuura, Kentaro
Kleiner, David E.
Zamboni, Fausto
Alter, Harvey J.
Farci, Patrizia
TI Analysis of long noncoding RNA expression in hepatocellular carcinoma of
different viral etiology
SO JOURNAL OF TRANSLATIONAL MEDICINE
LA English
DT Article
DE Hepatocellular carcinoma; Long noncoding RNA; Hepatitis B virus;
Hepatitis C virus; Hepatitis D virus
ID HEPATITIS-B-VIRUS; LIVER-CANCER; PROMOTES PROLIFERATION;
CELL-PROLIFERATION; SIGNALING PATHWAY; TUMOR-GROWTH; METASTASIS;
PROGRESSION; CONTRIBUTES; ACTIVATION
AB Background: Dysregulation of long noncoding RNA (lncRNA) expression contributes to the pathogenesis of many human diseases, including liver diseases. Several lncRNAs have been reported to play a role in the development of hepatocellular carcinoma (HCC). However, most studies have analyzed lncRNAs only in hepatitis B virus (HBV)-related HCC or in a single group of HCC patients regardless of the viral etiology.
Methods: To investigate whether lncRNAs are differentially expressed in HCC of different viral etiology, we profiled 101 disease-related lncRNAs, including 25 lncRNAs previously associated with HCC, in liver specimens obtained from well-characterized patients with HBV-, hepatitis C virus (HCV)-, or hepatitis D virus (HDV)-associated HCC.
Results: We identified eight novel HCC-related lncRNAs that were significantly dysregulated in HCC tissues compared to their surrounding non-tumorous tissues. Some of these lncRNAs were significantly dysregulated predominantly in one specific hepatitis virus-related HCC, including PCAT-29 in HBV-related HCC, aHIF and PAR5 in HCV-related HCC, and Y3 in HDV-related HCC. Among the lncRNAs previously reported in HCC, we found that DBH-AS1, hDREH and hPVT1 were differentially expressed in HCC of different viral etiology.
Conclusions: Our study suggests that HCC of different viral etiology is regulated by different lncRNAs. The identification of lncRNAs unique to specific hepatitis virus-related HCC may provide new tools for improving the diagnosis of HCC and open new avenues for disease-specific therapeutic interventions.
C1 [Zhang, Quan; Farci, Patrizia] NIAID, Infect Dis Lab, Hepat Pathogenesis Sect, NIH, Bethesda, MD 20892 USA.
[Matsuura, Kentaro; Alter, Harvey J.] NIH, Dept Transfus Med, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA.
[Kleiner, David E.] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA.
[Zamboni, Fausto] Brotzu Hosp, Liver Transplantat Ctr, Cagliari, Italy.
[Zhang, Quan] Nanjing Univ, Dept Expt Med & Infect Dis, Nanjing Drum Tower Hosp, Sch Med, 321 Zhongshan Rd, Nanjing 210008, Jiangsu, Peoples R China.
RP Farci, P (reprint author), NIAID, Infect Dis Lab, Hepat Pathogenesis Sect, NIH, Bethesda, MD 20892 USA.
EM pfarci@niaid.nih.gov
FU Intramural Research Program of the National Institutes of Health,
National Institute of Allergy and Infectious Diseases, Clinical Center,
and National Cancer Institute
FX This research was supported by the Intramural Research Program of the
National Institutes of Health, National Institute of Allergy and
Infectious Diseases, Clinical Center, and National Cancer Institute.
NR 53
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Z9 0
U1 2
U2 2
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 NOV 28
PY 2016
VL 14
AR 328
DI 10.1186/s12967-016-1085-4
PG 11
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA EG5EB
UT WOS:000391065200001
PM 27894309
ER
PT J
AU Prema, A
Thenmozhi, AJ
Manivasagam, T
Essa, MM
Akbar, MD
Akbar, M
AF Prema, Asokan
Thenmozhi, Arokiasamy Justin
Manivasagam, Thamilarasan
Essa, Musthafa Mohamed
Akbar, Mohammed D.
Akbar, Mohammed
TI Fenugreek Seed Powder Nullified Aluminium Chloride Induced Memory Loss,
Biochemical Changes, A beta Burden and Apoptosis via Regulating Akt/GSK3
beta Signaling Pathway
SO PLOS ONE
LA English
DT Article
ID GLYCOGEN-SYNTHASE KINASE-3-BETA; ALZHEIMERS-DISEASE; RAT-BRAIN; NEURONAL
SURVIVAL; PROTEIN-KINASE; PHOSPHORYLATION; ACETYLCHOLINESTERASE;
NEUROTOXICITY; EXTRACT; DEATH
AB Alzheimer's disease (AD) is the most common form of dementia that mainly affects the cognitive functions of the aged populations. Trigonella foenum-graecum (L.) (fenugreek), a traditionally well utilized medicinal plant ubiquitously used as one of the main food additive worldwide, is known to have numerous beneficial health effects. Fenugreek seed extract could be able to inhibit the activity of acetylcholinesterase (AChE), a key enzyme involved in the pathogenesis of AD, and further shown to have anti-parkinsonic effect. The present study was aimed to explore the neuroprotective effect of fenugreek seed powder (FSP) against aluminium chloride (AlCl3) induced experimental AD model. Administration of germinated FSP (2.5, 5 and 10% mixed with ground standard rat feed) protected AlCl3 induced memory and learning impairments, Al overload, AChE hyperactivity, amyloid beta (A beta) burden and apoptosis via activating Akt/GSK3 beta pathway. Our present data could confirm the neuroprotective effect of fenugreek seeds. Further these results could lead a possible therapeutics for the management of neurodegenerative diseases including AD in future.
C1 [Prema, Asokan; Thenmozhi, Arokiasamy Justin; Manivasagam, Thamilarasan] Annamalai Univ, Dept Biochem & Biotechnol, Fac Sci, Annamalainagar 608002, Tamil Nadu, India.
[Essa, Musthafa Mohamed] Sultan Qaboos Univ, CAMS, Dept Food Sci & Nutr, Muscat, Oman.
[Essa, Musthafa Mohamed] Sultan Qaboos Univ, Ageing & Dementia Res Grp, Muscat, Oman.
[Essa, Musthafa Mohamed] Food & Brain Res Fdn, Madras 600094, Tamil Nadu, India.
[Akbar, Mohammed D.; Akbar, Mohammed] NIAAA, SMPT, NIH, Rockville, MD 20852 USA.
RP Thenmozhi, AJ (reprint author), Annamalai Univ, Dept Biochem & Biotechnol, Fac Sci, Annamalainagar 608002, Tamil Nadu, India.
EM justinthenmozhi@rediffmail.com
FU University Grants Commission-Basic Science Research Fellowship, New
Delhi, India
FX We gratefully acknowledge the University Grants Commission-Basic Science
Research Fellowship, New Delhi, India for financial assistance. The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 71
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U1 2
U2 2
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD NOV 28
PY 2016
VL 11
IS 11
AR e0165955
DI 10.1371/journal.pone.0165955
PG 19
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EE3FE
UT WOS:000389472400013
PM 27893738
ER
PT J
AU Diarra, B
Goita, D
Tounkara, S
Sanogo, M
Baya, B
Togo, ACG
Maiga, M
Sarro, YS
Kone, A
Kone, B
M'Baye, O
Coulibaly, N
Kassambara, H
Cisse, A
Belson, M
Polis, MA
Otu, J
Gehre, F
Antonio, M
Dao, S
Siddiqui, S
Murphy, RL
de Jong, BC
Diallo, S
AF Diarra, B.
Goita, D.
Tounkara, S.
Sanogo, M.
Baya, B.
Togo, A. C. G.
Maiga, M.
Sarro, Y. S.
Kone, A.
Kone, B.
M'Baye, O.
Coulibaly, N.
Kassambara, H.
Cisse, A.
Belson, M.
Polis, M. A.
Otu, J.
Gehre, F.
Antonio, M.
Dao, S.
Siddiqui, S.
Murphy, R. L.
de Jong, B. C.
Diallo, S.
TI Tuberculosis drug resistance in Bamako, Mali, from 2006 to 2014
SO BMC INFECTIOUS DISEASES
LA English
DT Article
DE Tuberculosis Drug resistance; Bamako; Mali
AB Background: Although Drug resistance tuberculosis is not a new phenomenon, Mali remains one of the "blank" countries without systematic data.
Methods: Between 2006 and 2014, we enrolled pulmonary TB patients from local TB diagnostics centers and a university referral hospital in several observational cohort studies. These consecutive patients had first line drug susceptibility testing (DST) performed on their isolates. A subset of MDR was subsequently tested for second line drug resistance.
Results: A total of 1186 mycobacterial cultures were performed on samples from 522 patients, including 1105 sputa and 81 blood samples, yielding one or more Mycobacterium tuberculosis complex (Mtbc) positive cultures for 343 patients. Phenotypic DST was performed on 337 (98.3%) unique Mtbc isolates, of which 127 (37.7%) were resistant to at least one drug, including 75 (22.3%) with multidrug resistance (MDR). The overall prevalence of MDRTB was 3.4% among new patients and 66.3% among retreatment patients. Second line DST was available for 38 (50. 7%) of MDR patients and seven (18.4%) had resistance to either fluoroquinolones or second-line injectable drugs.
Conclusion: The drug resistance levels, including MDR, found in this study are relatively high, likely related to the selected referral population. While worrisome, the numbers remained stable over the study period. These findings prompt a nationwide drug resistance survey, as well as continuous surveillance of all retreatment patients, which will provide more accurate results on countrywide drug resistance rates and ensure that MDR patients access appropriate second line treatment.
C1 [Diarra, B.; Goita, D.; Tounkara, S.; Sanogo, M.; Baya, B.; Togo, A. C. G.; Maiga, M.; Sarro, Y. S.; Kone, A.; Kone, B.; M'Baye, O.; Coulibaly, N.; Kassambara, H.; Dao, S.; Diallo, S.] USTTB, SEREFO Program, Bamako, Mali.
[Cisse, A.] INRSP, Lab Natl Reference Mycobacteries LNR, Bamako, Mali.
[Belson, M.; Polis, M. A.; Siddiqui, S.] NIAID, CCRB, Div Clin Res, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Otu, J.; Gehre, F.; Antonio, M.] MRC, Vaccines & Immun Theme, Atlantic Blvd, Banjul, Gambia.
[Diarra, B.; Gehre, F.; de Jong, B. C.] Inst Trop Med, Dept Biomed Sci, Antwerp, Belgium.
[Antonio, M.] London Sch Hyg & Trop Med, Fac Infect & Trop Dis, London, England.
[Antonio, M.] Univ Warwick, Warwick Med Sch, Microbiol & Infect Unit, Coventry, W Midlands, England.
[Murphy, R. L.] Northwestern Univ, Global Hlth, Chicago, IL 60611 USA.
RP Diarra, B (reprint author), USTTB, SEREFO Program, Bamako, Mali.; Diarra, B (reprint author), Inst Trop Med, Dept Biomed Sci, Antwerp, Belgium.
EM bdiarra@icermali.org
FU Northwestern University (Chicago, IL, USA) [ACTG U01AI069471];
University of Sciences, Techniques and Technologies of Bamako (USTTB)
through NIH/R01 [R01AI110386]; European & Developing Countries Clinical
Trials Partnership (EDCTP); AIDS and Malaria (WANETAM) [CG_cb_07_41700,
MSI 2010_10800-01/08/2011-31/07/14]; European Research
Council-INTERRUPTB [311725]; TDR fellowship [B40072]; special programme
for research and training in tropical diseases; UNICEF; UNDP; World
Bank; WHO
FX This study was partially funded by the Northwestern University (Chicago,
IL, USA) through ACTG U01AI069471, the University of Sciences,
Techniques and Technologies of Bamako (USTTB) through NIH/R01 grant
R01AI110386, the European & Developing Countries Clinical Trials
Partnership (EDCTP) through the West African Node of Excellence for TB,
AIDS and Malaria (WANETAM) Grants numbers CG_cb_07_41700 and MSI
2010_10800-01/08/2011-31/07/14 and the European Research
Council-INTERRUPTB through grant nr.311725 (to B.d.J.). B.D. was
supported by a TDR fellowship, TIMS ID B40072, the special programme for
research and training in tropical diseases, co-sponsored by UNICEF,
UNDP, World Bank and WHO.
NR 13
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U1 0
U2 0
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2334
J9 BMC INFECT DIS
JI BMC Infect. Dis.
PD NOV 28
PY 2016
VL 16
AR 714
DI 10.1186/s12879-016-2060-7
PG 8
WC Infectious Diseases
SC Infectious Diseases
GA ED7WR
UT WOS:000389083000001
PM 27894266
ER
PT J
AU Van Doorslaer, K
Porter, S
McKinney, C
Stepp, WH
McBride, AA
AF Van Doorslaer, Koenraad
Porter, Samuel
McKinney, Caleb
Stepp, Wesley H.
McBride, Alison A.
TI Novel recombinant papillomavirus genomes expressing selectable genes
SO SCIENTIFIC REPORTS
LA English
DT Article
ID EPITHELIAL-CELL DIFFERENTIATION; IN-VIVO; TRANSGENE EXPRESSION;
VIRAL-DNA; VECTORS
AB Papillomaviruses infect and replicate in keratinocytes, but viral proteins are initially expressed at low levels and there is no effective and quantitative method to determine the efficiency of infection on a cell-to-cell basis. Here we describe human papillomavirus (HPV) genomes that express marker proteins (antibiotic resistance genes and Green Fluorescent Protein), and can be used to elucidate early stages in HPV infection of primary keratinocytes. To generate these recombinant genomes, the late region of the oncogenic HPV18 genome was replaced by CpG free marker genes. Insertion of these exogenous genes did not affect early replication, and had only minimal effects on early viral transcription. When introduced into primary keratinocytes, the recombinant marker genomes gave rise to drug-resistant keratinocyte colonies and cell lines, which maintained the extrachromosomal recombinant genome long-term. Furthermore, the HPV18 "marker" genomes could be packaged into viral particles (quasivirions) and used to infect primary human keratinocytes in culture. This resulted in the outgrowth of drug-resistant keratinocyte colonies containing replicating HPV18 genomes. In summary, we describe HPV18 marker genomes that can be used to quantitatively investigate many aspects of the viral life cycle.
C1 [Van Doorslaer, Koenraad; Porter, Samuel; McKinney, Caleb; Stepp, Wesley H.; McBride, Alison A.] NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA.
RP McBride, AA (reprint author), NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA.
EM AMCBRIDE@nih.gov
OI Van Doorslaer, Koenraad/0000-0002-2985-0733
FU Intramural Research Program of NIAID, NIH
FX The authors acknowledge Jameela Khan for generating the initial plasmids
used in this study. This research was supported by the Intramural
Research Program of the NIAID, NIH.
NR 25
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U1 1
U2 1
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2045-2322
J9 SCI REP-UK
JI Sci Rep
PD NOV 28
PY 2016
VL 6
AR 37782
DI 10.1038/srep37782
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA ED4CM
UT WOS:000388795000001
PM 27892937
ER
PT J
AU Seol, HS
Lee, SE
Song, JS
Lee, HY
Park, S
Kim, I
Singh, SR
Chang, S
Jang, SJ
AF Seol, Hyang Sook
Lee, Sang Eun
Song, Joon Seon
Lee, Hye Yong
Park, Sojung
Kim, Inki
Singh, Shree Ram
Chang, Suhwan
Jang, Se Jin
TI Glutamate release inhibitor, Riluzole, inhibited proliferation of human
hepatocellular carcinoma cells by elevated ROS production
SO CANCER LETTERS
LA English
DT Article
DE Hepatocellular carcinoma; Drug repositioning; Riluzole; ROS
ID RAF/MEK/ERK PATHWAY; ANTITUMOR-ACTIVITY; CANCER-CELLS; SORAFENIB;
ANGIOGENESIS; MIGRATION; INVASION; TUMORS
AB Liver cancer is one of the common malignancies in many countries and an increasing cause of cancer death. Despite of that, there are few therapeutic options available with inconsistent outcome, raising a need for developing alternative therapeutic options. Through a drug repositioning screening, we identified and investigated the action mechanism of the Riluzole, an amyotrophic lateral sclerosis (ALS) drug, on hepatocellular carcinoma (HCC) therapy. Treatment of the Riluzole leads to a suppression of cell proliferation in liver primary cancer cells and cancer cell lines. In addition, Riluzole induced caspase-dependent apoptosis and G2/M cell cycle arrest in SNU449 and Huh7 cell lines. In a line with the known function of glutamate release inhibitor, we found Riluzole-treated cells have increased the level of inner cellular glutamate that in turn decrease the glutathione (GSH) level and finally augment the reactive oxygen species (ROS) production. We confirm this finding in vivo by showing the Riluzole-induced GSH and ROS changes in a Huh7 xenograft cancer model. Altogether, these data suggest the anti-cancer effect of Riluzole on hepatocellular carcinoma and the suppression of glutamate signaling might be a new target pathway for HCC therapy. Published by Elsevier Ireland Ltd.
C1 [Seol, Hyang Sook; Lee, Sang Eun; Lee, Hye Yong; Park, Sojung; Kim, Inki] Univ Ulsan, Asan Inst Life Sci, Asan Med Ctr, Coll Med, Seoul, South Korea.
[Song, Joon Seon] Univ Ulsan, Dept Pathol, Asan Med Ctr, Coll Med, Seoul, South Korea.
[Singh, Shree Ram] NCI, Basic Res Lab, Stem Cell Regulat & Anim Aging Sect, Ctr Canc Res, Frederick, MD 21701 USA.
[Chang, Suhwan] Univ Ulsan, Dept Biomed Sci, Coll Med, Asan Med Ctr, Seoul, South Korea.
[Jang, Se Jin] Univ Ulsan, Asan Inst Life Sci, Dept Pathol, Coll Med,Asan Med Ctr, Seoul, South Korea.
RP Chang, S (reprint author), Univ Ulsan, Dept Biomed Sci, Coll Med, Asan Med Ctr, Seoul, South Korea.; Jang, SJ (reprint author), Univ Ulsan, Asan Inst Life Sci, Dept Pathol, Coll Med,Asan Med Ctr, Seoul, South Korea.
EM singhshr@mail.nih.gov; suhwan.chang@amc.seoul.kr; jangsejin@amc.seoul.kr
FU Basic Science Research Program through the National Research Foundation
of Korea (NRF) - Ministry of Science, ICT and Future Planning
[2015R1A1A3A04001354]; Korea Health Technology R&D Project through the
Korea Health Industry Development Institute (KHIDI) - Ministry of Health
&Welfare, Republic of Korea [HI06C0868, HI13C1538]
FX This research was supported by Basic Science Research Program through
the National Research Foundation of Korea (NRF) funded by the Ministry
of Science, ICT and Future Planning (2015R1A1A3A04001354), the Korea
Health Technology R&D Project through the Korea Health Industry
Development Institute (KHIDI) (grant numbers: HI06C0868, HI13C1538),
funded by the Ministry of Health &Welfare, Republic of Korea.
NR 19
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U1 12
U2 12
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0304-3835
EI 1872-7980
J9 CANCER LETT
JI Cancer Lett.
PD NOV 28
PY 2016
VL 382
IS 2
BP 157
EP 165
DI 10.1016/j.canlet.2016.08.028
PG 9
WC Oncology
SC Oncology
GA EB2NL
UT WOS:000387199000003
ER
PT J
AU Zhuang, J
Kamp, WM
Li, J
Liu, CY
Kang, JG
Wang, PY
Hwang, PM
AF Zhuang, Jie
Kamp, William M.
Li, Jie
Liu, Chengyu
Kang, Ju-Gyeong
Wang, Ping-Yuan
Hwang, Paul M.
TI Forkhead Box O3A (FOXO3) and the Mitochondrial Disulfide Relay Carrier
(CHCHD4) Regulate p53 Protein Nuclear Activity in Response to Exercise
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID SKELETAL-MUSCLE; ENDURANCE EXERCISE; PATHWAY; SIRT1; PHOSPHORYLATION;
TRANSLOCATION; HOMEOSTASIS; BIOGENESIS; METABOLISM; TURNOVER
AB Although exercise is linked with improved health, the specific molecular mechanisms underlying its various benefits require further clarification. Here we report that exercise increases the nuclear localization and activity of p53 by acutely down-regulating coiled-coil-helix-coiled-coil-helix domain 4 (CHCHD4), a carrier protein that mediates p53 import into the mitochondria. This response to exercise is lost in transgenic mice with constitutive expression of CHCHD4. Mechanistically, exercise-induced nuclear transcription factor FOXO3 binds to the CHCHD4 promoter and represses its expression, preventing the translocation of p53 to the mitochondria and thereby increasing p53 nuclear localization. The synergistic increase in nuclear p53 and FOXO3 by exercise can facilitate their known interaction in transactivating Sirtuin 1 (SIRT1), a NAD(+)-dependent histone deacetylase that mediates adaptation to various stresses. Thus, our results reveal one mechanism by which exercise could be involved in preventing cancer and potentially other diseases associated with aging.
C1 [Zhuang, Jie; Kamp, William M.; Li, Jie; Kang, Ju-Gyeong; Wang, Ping-Yuan; Hwang, Paul M.] NHLBI, Ctr Mol Med, NIH, Bldg 10, Bethesda, MD 20892 USA.
[Liu, Chengyu] NHLBI, Transgen Core, NIH, Bldg 10, Bethesda, MD 20892 USA.
RP Hwang, PM (reprint author), 10CRC 5-5330,10 Ctr Dr, Bethesda, MD 20892 USA.
EM hwangp@mail.nih.gov
FU Division of Intramural Research of the NHLBI, National Institutes of
Health [HL005101]
FX This work was supported by the Division of Intramural Research of the
NHLBI, National Institutes of Health Grant HL005101 (to P. M. H.). The
authors declare that they have no conflicts of interest with the
contents of this article. The content is solely the responsibility of
the authors and does not necessarily represent the official views of the
National Institutes of Health.
NR 37
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U1 6
U2 6
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
EI 1083-351X
J9 J BIOL CHEM
JI J. Biol. Chem.
PD NOV 25
PY 2016
VL 291
IS 48
BP 24819
EP +
DI 10.1074/jbc.M116.745737
PG 15
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA ED5GR
UT WOS:000388880100002
PM 27687729
ER
PT J
AU Liu, X
Shu, S
Billington, N
Williamson, CD
Yu, S
Brzeska, H
Donaldson, JG
Sellers, JR
Korn, ED
AF Liu, Xiong
Shu, Shi
Billington, Neil
Williamson, Chad D.
Yu, Shuhua
Brzeska, Hanna
Donaldson, Julie G.
Sellers, James R.
Korn, Edward D.
TI Mammalian Nonmuscle Myosin II Binds to Anionic Phospholipids with
Concomitant Dissociation of the Regulatory Light Chain
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID PROTEIN-KINASE-C; SMOOTH-MUSCLE MYOSIN; PHOSPHATIDYLINOSITOL
4,5-BISPHOSPHATE; TRANSPORT VESICLES; PLASMA-MEMBRANE; GOLGI MEMBRANES;
ATPASE ACTIVITY; IN-VITRO; PHOSPHORYLATION; ACTIN
AB Mammalian cells express three Class II nonmuscle myosins (NM): NM2A, NM2B, and NM2C. The three NM2s have well established essential roles in cell motility, adhesion, and cytokinesis and less well defined roles in vesicle transport and other processes that would require association of NM2s with cell membranes. Previous evidence for the mechanism of NM2-membrane association includes direct interaction of NM2s with membrane lipids and indirect interaction by association of NM2s with membrane-bound F-actin or peripheral membrane proteins. Direct binding of NM2s to phosphatidylserine-liposomes, but not to phosphatidylcholine-liposomes, has been reported, but the molecular basis of the interaction between NM2s and acidic phospholipids has not been previously investigated. We now show that filamentous, full-length NM2A, NM2B, and NM2C and monomeric, non-filamentous heavy meromyosin bind to liposomes containing one or more acidic phospholipids (phosphatidylserine, phosphatidylinositol 4,5-diphosphate, and phosphatidylinositol 3,4,5-triphosphate) but do not bind to 100% phosphatidylcholine-liposomes. Binding of NM2s to acidic liposomes occurs predominantly through interaction of the liposomes with the regulatory light chain (RLC) binding site in the myosin heavy chain with concomitant dissociation of the RLC. Phosphorylation of myosin-bound RLC by myosin light chain kinase substantially inhibits binding to liposomes of both filamentous NM2 and non-filamentous heavy meromyosin; the addition of excess unbound RLC, but not excess unbound essential light chain, competes with liposome binding. Consistent with the in vitro data, we show that endogenous and expressed NM2A associates with the plasma membrane of HeLa cells and fibrosarcoma cells independently of F-actin.
C1 [Liu, Xiong; Shu, Shi; Williamson, Chad D.; Yu, Shuhua; Brzeska, Hanna; Donaldson, Julie G.; Korn, Edward D.] NHLBI, Cell Biol Lab, NIH, Bldg 50,Rm 2517,9000 Rockville Pike, Bethesda, MD 20892 USA.
[Billington, Neil; Sellers, James R.] NHLBI, Labs Mol Physiol, NIH, Bldg 10, Bethesda, MD 20892 USA.
RP Korn, ED (reprint author), NHLBI, Cell Biol Lab, NIH, Bldg 50,Rm 2517,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM edk@nih.gov
FU Electron and Light Microscopy Cores of the NHLBI, National Institutes of
Health
FX We acknowledge the support of the Electron and Light Microscopy Cores of
the NHLBI, National Institutes of Health. We thank Dr. John Hammer 3rd
(NHLBI) for NM2A-mTomato and Dr. Fang Zhang (NHLBI) for purified myosin
light chain kinase.
NR 44
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U1 2
U2 2
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
EI 1083-351X
J9 J BIOL CHEM
JI J. Biol. Chem.
PD NOV 25
PY 2016
VL 291
IS 48
BP 24828
EP 24837
DI 10.1074/jbc.M116.739185
PG 10
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA ED5GR
UT WOS:000388880100003
PM 27697842
ER
PT J
AU Esser, L
Zhou, F
Zhou, YH
Xiao, YM
Tang, WK
Yu, CA
Qin, ZH
Xia, D
AF Esser, Lothar
Zhou, Fei
Zhou, Yihui
Xiao, Yumei
Tang, Wai-Kwan
Yu, Chang-An
Qin, Zhaohai
Xia, Di
TI Hydrogen Bonding to the Substrate Is Not Required for Rieske Iron-Sulfur
Protein Docking to the Quinol Oxidation Site of Complex III
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID CYTOCHROME BC(1) COMPLEX; BOVINE HEART-MITOCHONDRIA; X-RAY-STRUCTURE;
CRYSTAL-STRUCTURE; C REDUCTASE; RESPIRATORY-CHAIN; ELECTRON-TRANSFER;
Q-CYCLE; INHIBITORS; BINDING
AB Complex III or the cytochrome (cyt) bc(1) complex constitutes an integral part of the respiratory chain of most aerobic organisms and of the photosynthetic apparatus of anoxygenic purple bacteria. The function of cyt bc(1) is to couple the reaction of electron transfer from ubiquinol to cytochrome c to proton pumping across the membrane. Mechanistically, the electron transfer reaction requires docking of its Rieske iron-sulfur protein (ISP) subunit to the quinol oxidation site (Q(P)) of the complex. Formation of an H-bond between the ISP and the bound substrate was proposed to mediate the docking. Here we show that the binding of oxazolidinedione-type inhibitors famoxadone, jg144, and fenamidone induces docking of the ISP to the QP site in the absence of the H-bond formation both in mitochondrial and bacterial cyt bc(1) complexes, demonstrating that ISP docking is independent of the proposed direct ISP-inhibitor interaction. The binding of oxazolidinedione-type inhibitors to cyt bc(1) of different species reveals a toxophore that appears to interact optimally with residues in the Q(P) site. The effect of modifications or additions to the toxophore on the binding to cyt bc(1) from different species could not be predicted from structure-based sequence alignments, as demonstrated by the altered binding mode of famoxadone to bacterial cyt bc(1).
C1 [Esser, Lothar; Zhou, Fei; Zhou, Yihui; Xiao, Yumei; Tang, Wai-Kwan; Xia, Di] NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bldg 37, Bethesda, MD 20892 USA.
[Zhou, Yihui; Xiao, Yumei; Qin, Zhaohai] China Agr Univ, Coll Sci, Beijing 100193, Peoples R China.
[Yu, Chang-An] Oklahoma State Univ, Dept Biochem & Mol Biol, Stillwater, OK 74078 USA.
RP Xia, D (reprint author), NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bldg 37, Bethesda, MD 20892 USA.
EM xiad@mail.nih.gov
FU Intramural Research Program of the National Institutes of Health,
National Cancer Institute, Center for Cancer Research; National Basic
Research Science Foundation of China [2010CB126100]
FX This work was supported by the Intramural Research Program of the
National Institutes of Health, National Cancer Institute, Center for
Cancer Research, and a grant from the National Basic Research Science
Foundation of China (2010CB126100) (to Z. Q.). The authors declare that
they have no conflicts of interest with the contents of this article.
The content is solely the responsibility of the authors and does not
necessarily represent the official views of the National Institutes of
Health.
NR 44
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U1 11
U2 11
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
EI 1083-351X
J9 J BIOL CHEM
JI J. Biol. Chem.
PD NOV 25
PY 2016
VL 291
IS 48
BP 25019
EP 25031
DI 10.1074/jbc.M116.744391
PG 13
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA ED5GR
UT WOS:000388880100019
PM 27758861
ER
PT J
AU Speen, AM
Kim, HYH
Bauer, RN
Meyer, M
Gowdy, KM
Fessler, MB
Duncan, KE
Liu, W
Porter, NA
Jaspers, I
AF Speen, Adam M.
Kim, Hye-Young H.
Bauer, Rebecca N.
Meyer, Megan
Gowdy, Kymberly M.
Fessler, Michael B.
Duncan, Kelly E.
Liu, Wei
Porter, Ned A.
Jaspers, Ilona
TI Ozone-derived Oxysterols Affect Liver X Receptor (LXR) Signaling A
POTENTIAL ROLE FOR LIPID-PROTEIN ADDUCTS
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID AIRWAY EPITHELIAL-CELLS; BIOLOGICALLY-ACTIVE OXYSTEROLS; BRONCHOALVEOLAR
LAVAGE FLUID; LEMLI-OPITZ SYNDROME; NF-KAPPA-B; OZONATION PRODUCTS; LUNG
SURFACTANT; INNATE IMMUNITY; INFLAMMATORY MEDIATORS; OXIDIZED
PHOSPHOLIPIDS
AB When inhaled, ozone (O-3) interacts with cholesterols of airway epithelial cell membranes or the lung-lining fluid, generating chemically reactive oxysterols. The mechanism by which O-3-derived oxysterols affect molecular function is unknown. Our data show that in vitro exposure of human bronchial epithelial cells to O-3 results in the formation of oxysterols, epoxy-cholesterol-alpha and -beta and secosterol A and B (Seco A and Seco B), in cell lysates and apical washes. Similarly, bronchoalveolar lavage fluid obtained from human volunteers exposed to O-3 contained elevated levels of these oxysterol species. As expected, O-3-derived oxysterols have a pro-inflammatory effect and increase NF-kappa B activity. Interestingly, expression of the cholesterol efflux pump ATP-binding cassette transporter 1 (ABCA1), which is regulated by activation of the liver X receptor (LXR), was suppressed in epithelial cells exposed to O-3. Additionally, exposure of LXR knock-out mice to O-3 enhanced pro-inflammatory cytokine production in the lung, suggesting LXR inhibits O-3-induced inflammation. Using alkynyl surrogates of O-3-derived oxysterols, our data demonstrate adduction of LXR with Seco A. Similarly, supplementation of epithelial cells with alkynyl-tagged cholesterol followed by O-3 exposure causes observable lipid-LXR adduct formation. Experiments using Seco A and the LXR agonist T0901317 (T09) showed reduced expression of ABCA1 as compared with stimulation with T0901317 alone, indicating that Seco A-LXR protein adduct formation inhibits LXR activation by traditional agonists. Overall, these data demonstrate that O-3-derived oxysterols have pro-inflammatory functions and form lipid-protein adducts with LXR, thus leading to suppressed cholesterol regulatory gene expression and providing a biochemical mechanism mediating O-3-derived formation of oxidized lipids in the airways and subsequent adverse health effects.
C1 [Speen, Adam M.; Bauer, Rebecca N.; Meyer, Megan; Duncan, Kelly E.; Jaspers, Ilona] Univ N Carolina, Ctr Environm Med Asthma & Lung Biol, Dept Pediat, Curriculum Toxicol, Chapel Hill, NC 27599 USA.
[Speen, Adam M.; Bauer, Rebecca N.; Meyer, Megan; Duncan, Kelly E.; Jaspers, Ilona] Univ N Carolina, Ctr Environm Med Asthma & Lung Biol, Dept Microbiol & Immunol, Curriculum Toxicol, Chapel Hill, NC 27599 USA.
[Kim, Hye-Young H.; Liu, Wei; Porter, Ned A.] Vanderbilt Univ, Dept Chem, Box 1583, Nashville, TN 37235 USA.
[Kim, Hye-Young H.; Liu, Wei; Porter, Ned A.] Vanderbilt Univ, Ctr Mol Toxicol, Nashville, TN 37235 USA.
[Gowdy, Kymberly M.] East Carolina Univ, Brody Sch Med, Dept Pharmacol & Toxicol, Greenville, NC 27834 USA.
[Fessler, Michael B.] NIEHS, Immun Inflammat & Dis Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.
RP Jaspers, I (reprint author), Univ North Carolina Chapel Hill, Dept Pediat Microbiol & Immunol, 104 Mason Farm Rd, Chapel Hill, NC 27599 USA.; Jaspers, I (reprint author), Univ North Carolina Chapel Hill, Environm Sci & Engn, 104 Mason Farm Rd, Chapel Hill, NC 27599 USA.
EM ilona_jaspers@med.unc.edu
FU United States Environmental Protection Agency [CR83346301]; Center for
Environmental Medicine, Asthma and Lung Biology at the University of
North Carolina at Chapel Hill; National Institutes of Health
[T32ES007126, R21ES024666]
FX This work was supported in part by the United States Environmental
Protection Agency through cooperative agreement CR83346301 with the
Center for Environmental Medicine, Asthma and Lung Biology at the
University of North Carolina at Chapel Hill (to I. J. and K. E. D.) and
National Institutes of Health Grants T32ES007126 (to A. M. S. and R. N.
B.) and R21ES024666 (to H. Y. K., N. A. P., and I. J.). The authors
declare that they have no conflicts of interest with the contents of
this article. This article has not been formally reviewed by EPA. The
views expressed in this document are solely those of the authors and do
not necessarily reflect those of the Agency. EPA does not endorse any
products or commercial services mentioned in this publication. The
content is solely the responsibility of the authors and does not
necessarily represent the official views of the National Institutes of
Health.
NR 76
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U1 4
U2 4
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
EI 1083-351X
J9 J BIOL CHEM
JI J. Biol. Chem.
PD NOV 25
PY 2016
VL 291
IS 48
BP 25192
EP 25206
DI 10.1074/jbc.M116.732362
PG 15
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA ED5GR
UT WOS:000388880100033
PM 27703007
ER
PT J
AU Koga, T
Yao, PL
Goudarzi, M
Murray, IA
Balandaram, G
Gonzalez, FJ
Perdew, GH
Fornace, AJ
Peters, JM
AF Koga, Takayuki
Yao, Pei-Li
Goudarzi, Maryam
Murray, Iain A.
Balandaram, Gayathri
Gonzalez, Frank J.
Perdew, Gary H.
Fornace, Albert J., Jr.
Peters, Jeffrey M.
TI Regulation of Cytochrome P450 2B10 (CYP2B10) Expression in Liver by
Peroxisome Proliferator-activated Receptor-beta/delta Modulation of SP1
Promoter Occupancy
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID CONSTITUTIVE ANDROSTANE RECEPTOR; PPAR-DELTA AGONIST; NUCLEAR
TRANSLOCATION; LIGAND ACTIVATION; CELLS; DISEASE; ALPHA; CAR; MICE; GENE
AB Alcoholic liver disease is a pathological condition caused by overconsumption of alcohol. Because of the high morbidity and mortality associated with this disease, there remains a need to elucidate the molecular mechanisms underlying its etiology and to develop new treatments. Because peroxisome proliferator-activated receptor-beta/delta (PPAR beta/delta) modulates ethanol-induced hepatic effects, the present study examined alterations in gene expression that may contribute to this disease. Chronic ethanol treatment causes increased hepatic CYP2B10 expression in Ppar beta/delta(+/+) mice but not in Ppar beta/delta(-/-) mice. Nuclear and cytosolic localization of the constitutive androstane receptor (CAR), a transcription factor known to regulate Cyp2b10 expression, was not different between genotypes. PPAR gamma co-activator 1 alpha, a co-activator of both CAR and PPAR beta/delta, was up-regulated in Ppar beta/delta(+/+) liver following ethanol exposure, but not in Ppar beta/delta(-/-) liver. Functional mapping of the Cyp2b10 promoter and ChIP assays revealed that PPAR beta/delta-dependent modulation of SP1 promoter occupancy up-regulated Cyp2b10 expression in response to ethanol. These results suggest that PPAR beta/delta regulates Cyp2b10 expression indirectly by modulating SP1 and PPAR gamma co-activator 1 alpha expression and/or activity independent of CAR activity. Ligand activation of PPAR beta/delta attenuates ethanol-induced Cyp2b10 expression in Ppar beta/delta(+/+) liver but not in Ppar beta/delta(-/-) liver. Strikingly, Cyp2b10 suppression by ligand activation of PPAR beta/delta following ethanol treatment occurred in hepatocytes and was mediated by paracrine signaling from Kupffer cells. Combined, results from the present study demonstrate a novel regulatory role of PPAR beta/delta in modulating CYP2B10 that may contribute to the etiology of alcoholic liver disease.
C1 [Koga, Takayuki; Yao, Pei-Li; Murray, Iain A.; Balandaram, Gayathri; Perdew, Gary H.; Peters, Jeffrey M.] Penn State Univ, Dept Vet & Biomed Sci, 312 Life Sci Bldg, University Pk, PA 16802 USA.
[Koga, Takayuki; Yao, Pei-Li; Murray, Iain A.; Balandaram, Gayathri; Perdew, Gary H.; Peters, Jeffrey M.] Penn State Univ, Ctr Mol Toxicol & Carcinogenesis, 312 Life Sci Bldg, University Pk, PA 16802 USA.
[Goudarzi, Maryam; Fornace, Albert J., Jr.] Georgetown Univ, Dept Biochem & Mol & Cellular Biol, Washington, DC 20057 USA.
[Gonzalez, Frank J.] NCI, Lab Metab, Bethesda, MD 20892 USA.
RP Peters, JM (reprint author), Penn State Univ, Dept Vet & Biomed Sci, 312 Life Sci Bldg, University Pk, PA 16802 USA.; Peters, JM (reprint author), Penn State Univ, Ctr Mol Toxicol & Carcinogenesis, 312 Life Sci Bldg, University Pk, PA 16802 USA.
EM jmp21@psu.edu
FU National Institute of Alcohol Abuse and Alcoholism [CA124533, CA141029,
AA018863]; National Institutes of Health NCI Intramural Research Program
[ZIABC005561, ZIABC005562, ZIABC005708]
FX This work was supported by National Institute of Alcohol Abuse and
Alcoholism Grants CA124533 and CA141029 (to J. M. P.) and AA018863 (to
A. J. F. and J. M. P.) and National Institutes of Health NCI Intramural
Research Program Grants ZIABC005561, ZIABC005562, and ZIABC005708 (to F.
J. G.). The authors declare that they have no conflicts of interest with
the contents of this article. The content is solely the responsibility
of the authors and does not necessarily represent the official views of
the National Institutes of Health.
NR 42
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U2 1
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
EI 1083-351X
J9 J BIOL CHEM
JI J. Biol. Chem.
PD NOV 25
PY 2016
VL 291
IS 48
BP 25255
EP 25263
DI 10.1074/jbc.M116.755447
PG 9
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA ED5GR
UT WOS:000388880100039
PM 27765815
ER
PT J
AU Rotroff, DM
Joubert, BR
Marvel, SW
Haberg, SE
Wu, MC
Nilsen, RM
Ueland, PM
Nystad, W
London, SJ
Motsinger-Reif, A
AF Rotroff, Daniel M.
Joubert, Bonnie R.
Marvel, Skylar W.
Haberg, Siri E.
Wu, Michael C.
Nilsen, Roy M.
Ueland, Per M.
Nystad, Wenche
London, Stephanie J.
Motsinger-Reif, Alison
TI Maternal smoking impacts key biological pathways in newborns through
epigenetic modification in Utero
SO BMC GENOMICS
LA English
DT Article
DE Smoking; Epigenetics; Pathway analysis; Cancer; In utero
ID DNA METHYLATION; PRENATAL EXPOSURE; NORWEGIAN MOTHER; CHILDHOOD-CANCER;
PARENTAL SMOKING; WIDE ASSOCIATION; COHORT PROFILE; RECEPTOR-ALPHA;
PREGNANCY; ESTROGEN
AB Background: Children exposed to maternal smoking during pregnancy exhibit increased risk for many adverse health effects. Maternal smoking influences methylation in newborns at specific CpG sites (CpGs). Here, we extend evaluation of individual CpGs to gene-level and pathway-level analyses among 1062 participants in the Norwegian Mother and Child Cohort Study (MoBa) using the Illumina 450 K platform to measure methylation in newborn DNA and maternal smoking in pregnancy, assessed using the biomarker, plasma cotinine. We used novel implementations of bioinformatics tools to collapse epigenome-wide methylation data into gene-and pathway-level effects to test whether exposure to maternal smoking in utero differentially methylated CpGs in genes enriched in biologic pathways. Unlike most pathway analysis applications, our approach allows replication in an independent cohort.
Results: Data on 485,577 CpGs, mapping to a total of 20,199 genes, were used to create gene scores that were tested for association with maternal plasma cotinine levels using Sequence Kernel Association Test (SKAT), and 15 genes were found to be associated (q < 0.25). Six of these 15 genes (GFI1, MYO1G, CYP1A1, RUNX1, LCTL, and AHRR) contained individual CpGs that were differentially methylated with regards to cotinine levels (p < 1.06 x 10(-7)). Nine of the 15 genes (FCRLA, MIR641, SLC25A24, TRAK1, C1orf180, ITLN2, GLIS1, LRFN1, and MIR451) were associated with cotinine at the gene-level (q < 0.25) but had no genome-wide significant individual CpGs (p > 1.06 x 10(-7)). Pathway analyses using gene scores resulted in 51 significantly associated pathways, which we tested for replication in an independent cohort (q < 0.05). Of those 32 replicated in an independent cohort, which clustered into six groups. The largest cluster consisted of pathways related to cancer, cell cycle, ERa receptor signaling, and angiogenesis. The second cluster, organized into five smaller pathway groups, related to immune system function, such as T-cell regulation and other white blood cell related pathways.
Conclusions: Here we use novel implementations of bioinformatics tools to determine biological pathways impacted through epigenetic changes in utero by maternal smoking in 1062 participants in the MoBa, and successfully replicate these findings in an independent cohort. The results provide new insight into biological mechanisms that may contribute to adverse health effects from exposure to tobacco smoke in utero.
C1 [Joubert, Bonnie R.; London, Stephanie J.] NIEHS, Div Intramural Res, NIH, Dept Hlth & Human Serv, POB 12233,MD A3-05, Res Triangle Pk, NC 27709 USA.
[Rotroff, Daniel M.; Marvel, Skylar W.; Motsinger-Reif, Alison] North Carolina State Univ, Bioinformat Res Ctr, Raleigh, NC USA.
[Rotroff, Daniel M.] North Carolina State Univ, Dept Stat, Raleigh, NC USA.
[Haberg, Siri E.; Nystad, Wenche] Norwegian Inst Publ Hlth, Oslo, Norway.
[Wu, Michael C.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, 1124 Columbia St, Seattle, WA 98104 USA.
[Nilsen, Roy M.] Haukeland Hosp, Ctr Clin Res, Bergen, Norway.
[Ueland, Per M.] Univ Bergen, Dept Clin Sci, Bergen, Norway.
[Ueland, Per M.] Haukeland Hosp, Lab Clin Biochem, Bergen, Norway.
[Motsinger-Reif, Alison] North Carolina State Univ, Ctr Comparat Med & Translat Res, Raleigh, NC USA.
RP London, SJ (reprint author), NIEHS, Div Intramural Res, NIH, Dept Hlth & Human Serv, POB 12233,MD A3-05, Res Triangle Pk, NC 27709 USA.
EM London2@niehs.nih.gov
OI London, Stephanie/0000-0003-4911-5290; Wu, Michael
C./0000-0002-3357-6570
FU Norwegian Ministry of Health and Care Services; Ministry of Education
and Research; NIH/NIEHS [N01-ES-75558]; NIH/NINDS [1 UO1 NS 047537-01, 2
UO1 NS 047537-06A1]; Intramural Research Program of the NIH, National
Institute of Environmental Health Sciences [Z01-ES-49019]; Norwegian
Research Council/BIOBANK [221097]
FX The Norwegian Mother and Child Cohort Study are supported by the
Norwegian Ministry of Health and Care Services and the Ministry of
Education and Research, NIH/NIEHS (contract no N01-ES-75558), NIH/NINDS
(grant no. 1 UO1 NS 047537-01 and grant no. 2 UO1 NS 047537-06A1). For
this work, MoBa 1 and 2 were supported by the Intramural Research
Program of the NIH, National Institute of Environmental Health Sciences
(Z01-ES-49019) and the Norwegian Research Council/BIOBANK (grant no
221097). We are grateful to all the participating families in Norway who
take part in this on-going cohort study.
NR 52
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U1 13
U2 13
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2164
J9 BMC GENOMICS
JI BMC Genomics
PD NOV 25
PY 2016
VL 17
AR 976
DI 10.1186/s12864-016-3310-1
PG 12
WC Biotechnology & Applied Microbiology; Genetics & Heredity
SC Biotechnology & Applied Microbiology; Genetics & Heredity
GA ED3UG
UT WOS:000388773400006
PM 27887572
ER
PT J
AU Shenoy, S
Eapen, M
Panepinto, JA
Logan, BR
Wu, J
Abraham, A
Brochstein, J
Chaudhury, S
Godder, K
Haight, AE
Kasow, KA
Leung, K
Andreansky, M
Bhatia, M
Dalal, J
Haines, H
Jaroscak, J
Lazarus, HM
Levine, JE
Krishnamurti, L
Margolis, D
Megason, GC
Yu, LC
Pulsipher, MA
Gersten, I
DiFronzo, N
Horowitz, MM
Walters, MC
Kamani, N
AF Shenoy, Shalini
Eapen, Mary
Panepinto, Julie A.
Logan, Brent R.
Wu, Juan
Abraham, Allistair
Brochstein, Joel
Chaudhury, Sonali
Godder, Kamar
Haight, Ann E.
Kasow, Kimberly A.
Leung, Kathryn
Andreansky, Martin
Bhatia, Monica
Dalal, Jignesh
Haines, Hilary
Jaroscak, Jennifer
Lazarus, Hillard M.
Levine, John E.
Krishnamurti, Lakshmanan
Margolis, David
Megason, Gail C.
Yu, Lolie C.
Pulsipher, Michael A.
Gersten, Iris
DiFronzo, Nancy
Horowitz, Mary M.
Walters, Mark C.
Kamani, Naynesh
TI A trial of unrelated donor marrow transplantation for children with
severe sickle cell disease
SO BLOOD
LA English
DT Article
ID CORD BLOOD TRANSPLANTATION; VERSUS-HOST-DISEASE; QUALITY-OF-LIFE;
APLASTIC-ANEMIA; CONDITIONING REGIMEN; RISK-FACTORS; THALASSEMIA;
THERAPY; IMPACT; HEMOGLOBINOPATHIES
AB Children with sickle cell disease experience organ damage, impaired quality of life, and premature mortality. Allogeneic bone marrow transplant from an HLA-matched sibling can halt disease progression but is limited by donor availability. A Blood and Marrow Transplant Clinical Trials Network (BMT CTN) phase 2 trial conducted from 2008 to 2014 enrolled 30 children aged 4 to 19 years; 29 were eligible for evaluation. The primary objective was 1-year event-free survival (EFS) after HLA allele-matched (at HLA-A, -B, -C, and -DRB1 loci) unrelated donor transplant. The conditioning regimen included alemtuzumab, fludarabine, and melphalan. Graft-versus-host disease (GVHD) prophylaxis included calcineurin inhibitor, short-course methotrexate, and methylprednisolone. Transplant indications included stroke (n = 12), transcranial Doppler velocity >200 cm/s (n = 2), >= 3 vaso-occlusive pain crises per year (n = 12), or >= 2 acute chest syndrome episodes (n = 4) in the 2 years preceding enrollment. Median follow-up was 26 months (range, 12-62 months); graft rejection was 10%. The 1- and 2-year EFS rates were 76% and 69%, respectively. The corresponding rates for overall survival were 86% and 79%. The day 100 incidence rate of grade II-IV acute GVHD was 28%, and the 1-year incidence rate of chronic GVHD was 62%; 38% classified as extensive. There were 7 GVHD-related deaths. A 34% incidence of posterior reversible encephalopathy syndrome was noted in the first 6 months. Although the 1-year EFS met the prespecified target of >= 75%, this regimen cannot be considered sufficiently safe for widespread adoption without modifications to achieve more effective GVHD prophylaxis. The BMT CTN #0601 trial was registered at www.clinicaltrials.gov as #NCT00745420.
C1 [Shenoy, Shalini] Washington Univ, St Louis Childrens Hosp, Sch Med, Dept Pediat, St Louis, MO 63110 USA.
[Eapen, Mary; Panepinto, Julie A.; Logan, Brent R.; Horowitz, Mary M.] Med Coll Wisconsin, Dept Pediat, 8701 Watertown Plank Rd, Milwaukee, WI 53226 USA.
[Panepinto, Julie A.; Margolis, David] Childrens Hosp Wisconsin, Milwaukee, WI 53201 USA.
[Wu, Juan; Gersten, Iris] Emmes Corp, Rockville, MD USA.
[Abraham, Allistair] Childrens Natl Med Ctr, Washington, DC 20010 USA.
[Brochstein, Joel] Steven & Alexandra Cohen Childrens Med Ctr, New Hyde Pk, NY USA.
[Chaudhury, Sonali] Ann & Robert H Lurie Childrens Hosp Chicago, Chicago, IL USA.
[Godder, Kamar] Virginia Commonwealth Univ, Dept Pediat, Richmond, VA USA.
[Haight, Ann E.] Emory Univ, Sch Med, Dept Pediat, Childrens Healthcare Atlanta, Atlanta, GA USA.
[Kasow, Kimberly A.] Univ North Carolina Chapel Hill, Dept Pediat, Chapel Hill, NC USA.
[Leung, Kathryn] Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA.
[Andreansky, Martin] Univ Miami, Dept Pediat, Miami, FL 33152 USA.
[Bhatia, Monica] Columbia Univ, Med Ctr, New York, NY USA.
[Dalal, Jignesh] Childrens Mercy Hosp & Clin, Kansas City, KS USA.
[Haines, Hilary] Univ Alabama Birmingham, Dept Pediat, Birmingham, AL USA.
[Jaroscak, Jennifer] Med Univ South Carolina, Dept Pediat, Charleston, SC USA.
[Lazarus, Hillard M.] Case Western Reserve Univ, Univ Hosp Case Med Ctr, Dept Internal Med, Cleveland, OH 44106 USA.
[Levine, John E.] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA.
[Levine, John E.] Univ Michigan, Dept Pediat, Ann Arbor, MI 48109 USA.
[Krishnamurti, Lakshmanan] Childrens Hosp Pittsburgh, Pittsburgh, PA 15213 USA.
[Megason, Gail C.] Univ Mississippi, Med Ctr, Jackson, MS 39216 USA.
[Yu, Lolie C.] Louisiana State Univ, Med Ctr, Childrens Hosp New Orleans, New Orleans, LA USA.
[Pulsipher, Michael A.] Pediat Blood & Marrow Transplant Consortium, Salt Lake City, UT USA.
[DiFronzo, Nancy] NHLBI, Bldg 10, Bethesda, MD 20892 USA.
[Walters, Mark C.] UCSF Benioff Childrens Hosp, Oakland, CA USA.
[Kamani, Naynesh] AABB Ctr Cellular Therapies, Bethesda, MD USA.
EM shenoy@wustl.edu
FU National Institutes of Health, National Heart, Lung, and Blood Institute
and National Cancer Institute [U10-HL069294]; National Marrow Donor
Program; Sickle Cell Disease Clinical Research Network; National Center
on Minority Health and Health Disparities; Pediatric Blood and Marrow
Transplant Consortium
FX This work was supported by a grant from the National Institutes of
Health, National Heart, Lung, and Blood Institute and National Cancer
Institute (U10-HL069294) to the Blood and Marrow Transplant Clinical
Trials Network, the National Marrow Donor Program, the Sickle Cell
Disease Clinical Research Network, the National Center on Minority
Health and Health Disparities, and the Pediatric Blood and Marrow
Transplant Consortium.
NR 56
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U1 0
U2 0
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA
SN 0006-4971
EI 1528-0020
J9 BLOOD
JI Blood
PD NOV 24
PY 2016
VL 128
IS 21
BP 2561
EP 2567
DI 10.1182/blood-2016-05-715870
PG 7
WC Hematology
SC Hematology
GA EI7AO
UT WOS:000392649400016
PM 27625358
ER
PT J
AU Hoppe, T
Minton, AP
AF Hoppe, Travis
Minton, Allen P.
TI Incorporation of Hard and Soft Protein-Protein Interactions into Models
for Crowding Effects in Binary and Ternary Protein Mixtures. Comparison
of Approximate Analytical Solutions with Numerical Simulation
SO JOURNAL OF PHYSICAL CHEMISTRY B
LA English
DT Article
ID BOVINE SERUM-ALBUMIN; IN-VITRO; PHYSIOLOGICAL CONSEQUENCES;
LIGHT-SCATTERING; EXCLUDED-VOLUME; STABILITY; ENVIRONMENTS; CELL;
ASSOCIATION; DEPENDENCE
AB In order to better understand how nonspecific interactions between solutes can modulate specific biochemical reactions taking place in complex media, we introduce a simplified model aimed at elucidating general principles. In this model, solutions containing two or three species of interacting globular proteins are modeled as a fluid of spherical particles interacting through square well potentials that qualitatively capture both steric hard core repulsion and longer-ranged attraction or repulsion. The excess chemical potential, or free energy of solvation, of each particle species is calculated as a function of species concentrations, particle radii, and square well interaction range and depth. The results of analytical models incorporating two-body and three-body interactions are compared with the estimates of free energy obtained via Widom insertion into simulated equilibrium square-well fluids. The analytical models agree well with results of numeric simulations carried out for a variety of model parameters and fluid compositions up to a total particle volume fraction of ca. 0.2.
C1 [Hoppe, Travis] NIDDK, Phys Chem Lab, NIH, US PHS, Bethesda, MD 20892 USA.
[Minton, Allen P.] NIDDK, Lab Biochem & Genet, NIH, US PHS, Bethesda, MD 20892 USA.
RP Minton, AP (reprint author), NIH, Bldg 8,Room 226, Bethesda, MD 20892 USA.
EM minton@helix.nih.gov
FU Division of Inframural Research of the National Institute of Diabetes
and Digestive and Kidney Diseases
FX This research was supported by the Division of Inframural Research of
the National Institute of Diabetes and Digestive and Kidney Diseases,
and utilized the computational resources of the NIH HPC Biowulf cluster
(http://hpc.nih.gov).
NR 44
TC 0
Z9 0
U1 6
U2 6
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 NOV 24
PY 2016
VL 120
IS 46
BP 11866
EP 11872
DI 10.1021/acs.jpcb.6b07736
PG 7
WC Chemistry, Physical
SC Chemistry
GA ED5TA
UT WOS:000388914000003
PM 27779417
ER
PT J
AU Bar, KJ
Sneller, MC
Harrison, LJ
Justement, JS
Overton, ET
Petrone, ME
Salantes, DB
Seamon, CA
Scheinfeld, B
Kwan, RW
Learn, GH
Proschan, MA
Kreider, EF
Blazkova, J
Bardsley, M
Refsland, EW
Messer, M
Clarridge, KE
Tustin, NB
Madden, PJ
Oden, KS
O'Dell, SJ
Jarocki, B
Shiakolas, AR
Tressler, RL
Doria-Rose, NA
Bailer, RT
Ledgerwood, JE
Capparelli, EV
Lynch, RM
Graham, BS
Moir, S
Koup, RA
Mascola, JR
Hoxie, JA
Fauci, AS
Tebas, P
Chun, TW
AF Bar, K. J.
Sneller, M. C.
Harrison, L. J.
Justement, J. S.
Overton, E. T.
Petrone, M. E.
Salantes, D. B.
Seamon, C. A.
Scheinfeld, B.
Kwan, R. W.
Learn, G. H.
Proschan, M. A.
Kreider, E. F.
Blazkova, J.
Bardsley, M.
Refsland, E. W.
Messer, M.
Clarridge, K. E.
Tustin, N. B.
Madden, P. J.
Oden, K. S.
O'Dell, S. J.
Jarocki, B.
Shiakolas, A. R.
Tressler, R. L.
Doria-Rose, N. A.
Bailer, R. T.
Ledgerwood, J. E.
Capparelli, E. V.
Lynch, R. M.
Graham, B. S.
Moir, S.
Koup, R. A.
Mascola, J. R.
Hoxie, J. A.
Fauci, A. S.
Tebas, P.
Chun, T-W
TI Effect of HIV Antibody VRC01 on Viral Rebound after Treatment
Interruption
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID BROADLY NEUTRALIZING ANTIBODIES; IMMUNODEFICIENCY-VIRUS-INFECTION;
ACTIVE ANTIRETROVIRAL THERAPY; MONOCLONAL-ANTIBODIES; CONTROLLED-TRIAL;
COMBINATION; PROTECTION; RESERVOIR; VIREMIA; POTENT
AB BACKGROUND
The discovery of potent and broadly neutralizing antibodies (bNAbs) against human immunodeficiency virus (HIV) has made passive immunization a potential strategy for the prevention and treatment of HIV infection. We sought to determine whether passive administration of VRC01, a bNAb targeting the HIV CD4-binding site, can safely prevent or delay plasma viral rebound after the discontinuation of antiretroviral therapy (ART).
METHODS
We conducted two open-label trials (AIDS Clinical Trials Group [ACTG] A5340 and National Institutes of Health [NIH] 15-I-0140) of the safety, side-effect profile, pharmacokinetic properties, and antiviral activity of VRC01 in persons with HIV infection who were undergoing interruption of ART.
RESULTS
A total of 24 participants were enrolled, and one serious alcohol-related adverse event occurred. Viral rebound occurred despite plasma VRC01 concentrations greater than 50 mu g per milliliter. The median time to rebound was 4 weeks in the A5340 trial and 5.6 weeks in the NIH trial. Study participants were more likely than historical controls to have viral suppression at week 4 (38% vs. 13%, P = 0.04 by a two-sided Fisher's exact test in the A5340 trial; and 80% vs. 13%, P<0.001 by a two-sided Fisher's exact test in the NIH trial) but the difference was not significant at week 8. Analyses of virus populations before ART as well as before and after ART interruption showed that VRC01 exerted pressure on rebounding virus, resulting in restriction of recrudescent viruses and selection for preexisting and emerging antibody neutralization-resistant virus.
CONCLUSIONS
VRC01 slightly delayed plasma viral rebound in the trial participants, as compared with historical controls, but it did not maintain viral suppression by week 8. In the small number of participants enrolled in these trials, no safety concerns were identified with passive immunization with a single bNAb (VRC01). (Funded by the National Institute of Allergy and Infectious Diseases and others; ACTG A5340 and NIH 15-I-0140 ClinicalTrials.gov numbers, NCT02463227 and NCT02471326.)
C1 [Bar, K. J.; Salantes, D. B.; Scheinfeld, B.; Learn, G. H.; Kreider, E. F.; Bardsley, M.; Hoxie, J. A.; Tebas, P.] Univ Penn, Philadelphia, PA 19104 USA.
[Tustin, N. B.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA.
[Sneller, M. C.; Justement, J. S.; Petrone, M. E.; Blazkova, J.; Refsland, E. W.; Clarridge, K. E.; Moir, S.; Fauci, A. S.; Chun, T-W] NIAID, Immunoregulat Lab, Bldg 10, Bethesda, MD 20892 USA.
[Proschan, M. A.] NIAID, Biostat Res Branch, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Madden, P. J.; O'Dell, S. J.; Shiakolas, A. R.; Doria-Rose, N. A.; Bailer, R. T.; Ledgerwood, J. E.; Lynch, R. M.; Graham, B. S.; Koup, R. A.; Mascola, J. R.] NIAID, Vaccine Res Ctr, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Tressler, R. L.] NIAID, Div Aids, Bethesda, MD 20892 USA.
[Seamon, C. A.; Kwan, R. W.] NIH, Bldg 10, Bethesda, MD 20892 USA.
[Seamon, C. A.; Kwan, R. W.] NIH, Ctr Clin, Dept Crit Care Med, Bethesda, MD 20892 USA.
[Oden, K. S.] AIDS Clin Trials Grp, Silver Spring, MD USA.
[Tressler, R. L.] Columbus Technol & Serv, Greenbelt, MD USA.
[Harrison, L. J.] Harvard TH Chan Sch Publ Hlth, Boston, MA USA.
[Overton, E. T.; Messer, M.] Univ Alabama Birmingham, Birmingham, AL USA.
[Jarocki, B.] Frontier Sci & Technol Res Fdn Inc, Amherst, NY USA.
[Capparelli, E. V.] Univ Calif San Diego, La Jolla, CA 92093 USA.
RP Bar, KJ (reprint author), Univ Penn, Dept Med, 502D Johnson Pavil,3610 Hamilton Walk, Philadelphia, PA 19104 USA.; Chun, TW (reprint author), NIAID, Immunoregulat Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM bark@mail.med.upenn.edu; twchun@nih.gov
FU National Institute of Allergy and Infectious Diseases (NIAID)
[U01AI068636]; Penn Center for AIDS Research [P30 AI045008]; Penn
Clinical Trials Unit [AI069534]; University of Alabama at Birmingham
(UAB) Center for AIDS Research [P30 AI027767]; UAB Clinical Trials Unit
[AI069452]; AIDS Clinical Trials Group Statistical and Data Analysis
Center [UM1 AI068634]; NIAID [1-R21-AI118431]; Ruth L. Kirschstein
National Research Service Award [F30 AI112426]; Intramural Research
Program of the NIAID, NIH
FX Supported by an award from the National Institute of Allergy and
Infectious Diseases (NIAID) (U01AI068636); grants from the Penn Center
for AIDS Research (P30 AI045008), the Penn Clinical Trials Unit
(AI069534), the University of Alabama at Birmingham (UAB) Center for
AIDS Research (P30 AI027767), the UAB Clinical Trials Unit (AI069452),
the AIDS Clinical Trials Group Statistical and Data Analysis Center (UM1
AI068634), the NIAID (1-R21-AI118431, for A5340 viral analyses); and a
Ruth L. Kirschstein National Research Service Award (F30 AI112426, to
Dr. Kreider). The National Institutes of Health (NIH) study was funded
by the Intramural Research Program of the NIAID, NIH.
NR 44
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Z9 5
U1 5
U2 5
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 NOV 24
PY 2016
VL 375
IS 21
BP 2037
EP 2050
DI 10.1056/NEJMoa1608243
PG 14
WC Medicine, General & Internal
SC General & Internal Medicine
GA EC9KU
UT WOS:000388464300006
PM 27959728
ER
PT J
AU Chen, L
Wilson, K
Goldlust, I
Mott, BT
Eastman, R
Davis, MI
Zhang, XH
McKnight, C
Klumpp-Thomas, C
Shinn, P
Simmons, J
Gormally, M
Michael, S
Thomas, CJ
Ferrer, M
Guha, R
AF Chen, Lu
Wilson, Kelli
Goldlust, Ian
Mott, Bryan T.
Eastman, Richard
Davis, Mindy I.
Zhang, Xiaohu
McKnight, Crystal
Klumpp-Thomas, Carleen
Shinn, Paul
Simmons, John
Gormally, Mike
Michael, Sam
Thomas, Craig J.
Ferrer, Marc
Guha, Rajarshi
TI mQC: A Heuristic Quality-Control Metric for High-Throughput Drug
Combination Screening
SO SCIENTIFIC REPORTS
LA English
DT Article
ID STATISTICAL PARAMETER; ASSAYS; MODEL; COMPLEXITY; DISCOVERY; SYNERGY
AB Quality control (QC) metrics are critical in high throughput screening (HTS) platforms to ensure reliability and confidence in assay data and downstream analyses. Most reported HTS QC metrics are designed for plate level or single well level analysis. With the advent of high throughput combination screening there is a need for QC metrics that quantify the quality of combination response matrices. We introduce a predictive, interpretable, matrix-level QC metric, mQC, based on a mix of data-derived and heuristic features. mQC accurately reproduces the expert assessment of combination response quality and correctly identifies unreliable response matrices that can lead to erroneous or misleading characterization of synergy. When combined with the plate-level QC metric, Z', mQC provides a more appropriate determination of the quality of a drug combination screen. Retrospective analysis on a number of completed combination screens further shows that mQC is able to identify problematic screens whereas plate-level QC was not able to. In conclusion, our data indicates that mQC is a reliable QC filter that can be used to identify problematic drug combinations matrices and prevent further analysis on erroneously active combinations as well as for troubleshooting failed screens. The R source code of mQC is available at http://matrix.ncats.nih.gov/mQC.
C1 [Chen, Lu; Wilson, Kelli; Goldlust, Ian; Mott, Bryan T.; Eastman, Richard; Zhang, Xiaohu; McKnight, Crystal; Klumpp-Thomas, Carleen; Shinn, Paul; Gormally, Mike; Michael, Sam; Thomas, Craig J.; Ferrer, Marc; Guha, Rajarshi] Natl Ctr Adv Translat Sci NCATS, Div Preclin Innovat, Rockville, MD 20850 USA.
[Davis, Mindy I.] NIAID, Rockville, MD 20852 USA.
[Simmons, John] NCI, Lab Canc Biol & Genet, Bethesda, MD 20892 USA.
RP Guha, R (reprint author), Natl Ctr Adv Translat Sci NCATS, Div Preclin Innovat, Rockville, MD 20850 USA.
EM guhar@mail.nih.gov
NR 32
TC 0
Z9 0
U1 2
U2 2
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2045-2322
J9 SCI REP-UK
JI Sci Rep
PD NOV 24
PY 2016
VL 6
AR 37741
DI 10.1038/srep37741
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA ED5PH
UT WOS:000388903700001
PM 27883049
ER
PT J
AU Smith, ME
Sanderson, SC
Brothers, KB
Myers, MF
McCormick, J
Aufox, S
Shrubsole, MJ
Garrison, NA
Mercaldo, ND
Schildcrout, JS
Clayton, EW
Antommaria, AHM
Basford, M
Brilliant, M
Connolly, JJ
Fullerton, SM
Horowitz, CR
Jarvik, GP
Kaufman, D
Kitchner, T
Li, RL
Ludman, EJ
McCarty, C
McManus, V
Stallings, S
Williams, JL
Holm, IA
AF Smith, Maureen E.
Sanderson, Saskia C.
Brothers, Kyle B.
Myers, Melanie F.
McCormick, Jennifer
Aufox, Sharon
Shrubsole, Martha J.
Garrison, Nanibaa A.
Mercaldo, Nathaniel D.
Schildcrout, Jonathan S.
Clayton, Ellen Wright
Antommaria, Armand H. Matheny
Basford, Melissa
Brilliant, Murray
Connolly, John J.
Fullerton, Stephanie M.
Horowitz, Carol R.
Jarvik, Gail P.
Kaufman, Dave
Kitchner, Terri
Li, Rongling
Ludman, Evette J.
McCarty, Catherine
McManus, Valerie
Stallings, Sarah
Williams, Janet L.
Holm, Ingrid A.
TI Conducting a large, multi-site survey about patients' views on broad
consent: challenges and solutions
SO BMC MEDICAL RESEARCH METHODOLOGY
LA English
DT Article
DE Survey; Consent; Multi-site; Genomics; Institutional Review Board;
Cognitive interviews; Pilot
ID INFORMED-CONSENT; EMERGE CONSORTIUM; GENETIC RESEARCH; GENOMIC RESEARCH;
PERSPECTIVES; PARTICIPANTS; PREFERENCES; POPULATION; EXPERIENCE; SAMPLES
AB Background: As biobanks play an increasing role in the genomic research that will lead to precision medicine, input from diverse and large populations of patients in a variety of health care settings will be important in order to successfully carry out such studies. One important topic is participants' views towards consent and data sharing, especially since the 2011 Advanced Notice of Proposed Rulemaking (ANPRM), and subsequently the 2015 Notice of Proposed Rulemaking (NPRM) were issued by the Department of Health and Human Services (HHS) and Office of Science and Technology Policy (OSTP). These notices required that participants consent to research uses of their de-identified tissue samples and most clinical data, and allowing such consent be obtained in a one-time, open-ended or "broad" fashion. Conducting a survey across multiple sites provides clear advantages to either a single site survey or using a large online database, and is a potentially powerful way of understanding the views of diverse populations on this topic.
Methods: A workgroup of the Electronic Medical Records and Genomics (eMERGE) Network, a national consortium of 9 sites (13 separate institutions, 11 clinical centers) supported by the National Human Genome Research Institute (NHGRI) that combines DNA biorepositories with electronic medical record (EMR) systems for large-scale genetic research, conducted a survey to understand patients' views on consent, sample and data sharing for future research, biobank governance, data protection, and return of research results.
Results: Working across 9 sites to design and conduct a national survey presented challenges in organization, meeting human subjects guidelines at each institution, and survey development and implementation. The challenges were met through a committee structure to address each aspect of the project with representatives from all sites. Each committee's output was integrated into the overall survey plan. A number of site-specific issues were successfully managed allowing the survey to be developed and implemented uniformly across 11 clinical centers.
Conclusions: Conducting a survey across a number of institutions with different cultures and practices is a methodological and logistical challenge. With a clear infrastructure, collaborative attitudes, excellent lines of communication, and the right expertise, this can be accomplished successfully.
C1 [Smith, Maureen E.; Aufox, Sharon] Northwestern Univ, Feinberg Sch Med, Ctr Genet Med, 645 N Michigan Ave, Chicago, IL 60611 USA.
[Sanderson, Saskia C.; Horowitz, Carol R.] Icahn Sch Med Mt Sinai, New York, NY 10029 USA.
[Sanderson, Saskia C.] UCL, London, England.
[Brothers, Kyle B.] Univ Louisville, Sch Med, Louisville, KY 40292 USA.
[Myers, Melanie F.; Antommaria, Armand H. Matheny] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45229 USA.
[McCormick, Jennifer] Penn State Coll Med, Hershey, PA USA.
[Shrubsole, Martha J.; Mercaldo, Nathaniel D.; Schildcrout, Jonathan S.; Clayton, Ellen Wright; Basford, Melissa; Stallings, Sarah] Vanderbilt Univ, Med Ctr, Nashville, TN USA.
[Shrubsole, Martha J.; Mercaldo, Nathaniel D.; Schildcrout, Jonathan S.; Clayton, Ellen Wright; Basford, Melissa; Stallings, Sarah] Vanderbilt Univ, 221 Kirkland Hall, Nashville, TN 37235 USA.
[Garrison, Nanibaa A.] Seattle Childrens Res Inst, Seattle, WA USA.
[Brilliant, Murray; Kitchner, Terri; McManus, Valerie] Marshfield Clin Res Fdn, Marshfield, WI USA.
[Connolly, John J.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA.
[Fullerton, Stephanie M.; Jarvik, Gail P.] Univ Washington, Seattle, WA 98195 USA.
[Kaufman, Dave; Li, Rongling] NHGRI, NIH, Bethesda, MD 20892 USA.
[Ludman, Evette J.] Grp Hlth Res Inst, Seattle, WA USA.
[McCarty, Catherine] Essentia Inst Rural Hlth, Duluth, MN USA.
[Williams, Janet L.] Geisinger Hlth Syst, Danville, PA USA.
[Holm, Ingrid A.] Harvard Med Sch, Boston Childrens Hosp, Boston, MA USA.
RP Smith, ME (reprint author), Northwestern Univ, Feinberg Sch Med, Ctr Genet Med, 645 N Michigan Ave, Chicago, IL 60611 USA.
EM m-smith6@northwestern.edu
FU NHGRI [U01HG006828, U01HG006830, U01HG006389, U01HG006382, U01HG006375,
3U01HG006379, U01HG006380, 3U01-HG006388, U01HG006378, 3U01HG006385];
NIH Office of the Director through the NIH Common Fund
[3U01HG006828-02S1, 3U01HG006830-02S1, 3U01HG006389-03S1,
3U01HG006382-03S1, 3U01HG006375-03S1, 3U01HG006379-03S1,
3U01HG006380-03S1, 3U01HG006388-03S1, 3U01HG006378-03S1,
3U01HG006385-03S1]
FX The CERC Survey project within the eMERGE Network was initiated and
funded by NHGRI: U01HG006828 (Cincinnati Children's Hospital Medical
Center/Boston Children's Hospital); U01HG006830 (Children's Hospital of
Philadelphia); U01HG006389 (Essentia Institute of Rural Health,
Marshfield Clinic Research Foundation and Pennsylvania State
University); U01HG006382 (Geisinger Clinic); U01HG006375 (Group Health
Cooperative/University of Washington); 3U01HG006379 (Mayo Clinic);
U01HG006380 (Icahn School of Medicine at Mount Sinai); 3U01-HG006388
(Northwestern University); U01HG006378 (Vanderbilt University Medical
Center); and 3U01HG006385 (Vanderbilt University Medical Center serving
as the Coordinating Center). Additional funding was provided by the NIH
Office of the Director through the NIH Common Fund, which is managed by
the OD/Office of Strategies Coordination (OSC), award numbers
3U01HG006828-02S1 (Cincinnati Children's Hospital Medical Center/Boston
Children's Hospital); 3U01HG006830-02S1 (Children's Hospital of
Philadelphia); 3U01HG006389-03S1 (Essentia Institute of Rural Health,
Marshfield Clinic Research Foundation and Pennsylvania State
University); 3U01HG006382-03S1 (Geisinger Clinic); 3U01HG006375-03S1
(Group Health Cooperative/University of Washington); 3U01HG006379-03S1
(Mayo Clinic); 3U01HG006380-03S1 (Icahn School of Medicine at Mount
Sinai); 3U01HG006388-03S1 (Northwestern University); 3U01HG006378-03S1
(Vanderbilt University Medical Center); and 3U01HG006385-03S1
(Vanderbilt University Medical Center serving as the Coordinating
Center).
NR 24
TC 1
Z9 1
U1 3
U2 3
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2288
J9 BMC MED RES METHODOL
JI BMC Med. Res. Methodol.
PD NOV 24
PY 2016
VL 16
AR 162
DI 10.1186/s12874-016-0263-7
PG 11
WC Health Care Sciences & Services
SC Health Care Sciences & Services
GA ED0ET
UT WOS:000388516500001
PM 27881091
ER
PT J
AU Koren, G
Clark, S
Hankins, GDV
Caritis, SN
Umans, JG
Miodovnik, M
Mattison, DR
Matok, I
AF Koren, Gideon
Clark, Shannon
Hankins, Gary D. V.
Caritis, Steve N.
Umans, Jason G.
Miodovnik, Menachem
Mattison, Donald R.
Matok, Ilan
TI Demonstration of early efficacy results of the delayed-release
combination of doxylamine-pyridoxine for the treatment of nausea and
vomiting of pregnancy
SO BMC PREGNANCY AND CHILDBIRTH
LA English
DT Article
ID RANDOMIZED-CONTROLLED-TRIAL; MANAGEMENT; BENDECTIN
AB Background: Nausea and vomiting of pregnancy (NVP) affects up to 80% of expecting mothers. In April 2013 the FDA approved the delayed-release combination of doxylamine succinate and pyridoxine hydrochloride (Diclegis r) for NVP, based in part, on the results of a phase III randomized trial demonstrating the efficacy of this drug combination [study drug marketed under the trade name Diclectin r in Canada and Diclegis r in the United States] compared to placebo in pregnant women. Study drug dosing occurred for 14 days, which is substantially longer than what has been performed in similar studies. The objective of this study was to evaluate, through secondary analysis, whether the primary measure of efficacy can be demonstrated after five days of treatment.
Methods: Women suffering from NVP were randomized to receive Diclegis r (n = 131) or placebo (n = 125) for 14 days at doses ranging from two to four tablets a day, based on a pre-specified titration protocol. The primary efficacy endpoint was the change in the validated Pregnancy-Unique Quantification of Emesis (PUQE) score at baseline versus Day 15 between Diclegis r -treated and placebo-treated women. For the present study, the change in PUQE score between baseline and Day 15 (end of the study) was compared to the changes observed for Days 3, 4, and 5.
Results: The use of delayed-release doxylamine succinate and pyridoxine hydrochloride tablets show improved NVP symptom control as compared to placebo on Days 3,4 and 5, with sustained efficacy until the end of the trial.
Conclusion: A four day study drug dosing trial with Diclegis r is sufficient to document efficacy, as the results are similar to those achieved after 14 study drug dosing days. The benefit seen at the earlier time validates drug efficacy and minimizes the natural course of improvement.
C1 [Koren, Gideon; Matok, Ilan] Univ Toronto, Toronto, ON, Canada.
[Koren, Gideon; Matok, Ilan] Univ Western Ontario, London, ON, Canada.
[Clark, Shannon; Hankins, Gary D. V.] Univ Texas Med Branch, Dept Obstet & Gynecol, Galveston, TX 77555 USA.
[Caritis, Steve N.] Univ Pittsburgh, Med Ctr, Dept Obstet & Gynecol, Pittsburgh, PA USA.
[Umans, Jason G.; Miodovnik, Menachem] Medstar Hlth Res Inst, Hyattsville, MD USA.
[Umans, Jason G.; Miodovnik, Menachem] Georgetown Howard Univ, Ctr Clin & Translat Sci, Washington, DC USA.
[Koren, Gideon; Clark, Shannon; Hankins, Gary D. V.; Caritis, Steve N.; Umans, Jason G.; Miodovnik, Menachem; Mattison, Donald R.] Eunice Kennedy Shriver Natl Inst Child & Human De, Obstetr Pharmacol Res Unit Network, Bethesda, MD USA.
[Matok, Ilan] Hebrew Univ Jerusalem, Fac Med, Sch Pharm, Div Clin Pharm,Inst Drug Res, Jerusalem, Israel.
RP Koren, G (reprint author), Univ Toronto, Toronto, ON, Canada.; Koren, G (reprint author), Univ Western Ontario, London, ON, Canada.
EM gidiup_2000@yahoo.com
FU Duchesnay Inc., Blainville Quebec
FX The study was funded by Duchesnay Inc., Blainville Quebec.
NR 24
TC 0
Z9 0
U1 1
U2 1
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2393
J9 BMC PREGNANCY CHILDB
JI BMC Pregnancy Childbirth
PD NOV 24
PY 2016
VL 16
AR 371
DI 10.1186/s12884-016-1172-9
PG 5
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA EC8XW
UT WOS:000388427400003
PM 27881103
ER
PT J
AU Kumar, A
Ganini, D
Mason, RP
AF Kumar, Ashutosh
Ganini, Douglas
Mason, Ronald P.
TI Role of cytochrome c in a-synuclein radical formation: implications of
a-synuclein in neuronal death in Maneb- and paraquat-induced model of
Parkinson's disease
SO MOLECULAR NEURODEGENERATION
LA English
DT Article
DE Cytochrome c; a-synuclein radical; Peroxidase; Parkinson's disease;
Immuno-spin trapping
ID LEWY BODY DISEASE; ALPHA-SYNUCLEIN; NEURODEGENERATIVE DISEASES;
OXIDATIVE-STRESS; CROSS-LINKING; CELL-DEATH; 2 PARTS; MICE; NITRATION;
BRAIN
AB Background: The pathological features of Parkinson's disease (PD) include an abnormal accumulation of asynuclein in the surviving dopaminergic neurons. Though PD is multifactorial, several epidemiological reports show an increased incidence of PD with co-exposure to pesticides such as Maneb and paraquat (MP). In pesticide-related PD, mitochondrial dysfunction and a-synuclein oligomers have been strongly implicated, but the link between the two has not yet been understood. Similarly, the biological effects of a-synuclein or its radical chemistry in PD is largely unknown. Mitochondrial dysfunction during PD pathogenesis leads to release of cytochrome c in the cytosol. Once in the cytosol, cytochrome c has one of two fates: It either binds to apaf1 and initiates apoptosis or can act as a peroxidase. We hypothesized that as a peroxidase, cytochrome c leaked out from mitochondria can form radicals on a-synuclein and initiate its oligomerization.
Method: Samples from controls, and MP co-exposed wild-type and a-synuclein knockout mice were studied using immuno-spin trapping, confocal microscopy, immunohistochemistry, and microarray experiments.
Results: Experiments with MP co-exposed mice showed cytochrome c release in cytosol and its co-localization with a-synuclein. Subsequently, we used immuno-spin trapping method to detect the formation of a-synuclein radical in samples from an in vitro reaction mixture consisting of cytochrome c, a-synuclein, and hydrogen peroxide. These experiments indicated that cytochrome c plays a role in a-synuclein radical formation and oligomerization. Experiments with MP co-exposed a-synuclein knockout mice, in which cytochrome c-a synuclein co-localization and interaction cannot occur, mice showed diminished protein radical formation and neuronal death, compared to wild-type MP coexposed mice. Microarray data from MP co-exposed wild-type and a-synuclein knockout mice further showed that the absence of a-synuclein per se or its co-localization with cytochrome c confers protection from MP co-exposure, as several important pathways were unaffected in a-synuclein knockout mice.
Conclusions: Altogether, these results show that peroxidase activity of cytochrome c contributes to a-synuclein radical formation and oligomerization, and that a-synuclein, through its co-localization with cytochrome c or on its own, affects several biological pathways which contribute to increased neuronal death in an MP-induced model of PD.
C1 [Kumar, Ashutosh; Ganini, Douglas; Mason, Ronald P.] NIEHS, Free Radical Biol Grp, Immun Inflammat & Dis Lab, NIH, 111 TW Alexander Dr, Durham, NC 27709 USA.
RP Kumar, A (reprint author), NIEHS, Free Radical Biol Grp, Immun Inflammat & Dis Lab, NIH, 111 TW Alexander Dr, Durham, NC 27709 USA.
EM kumara10@niehs.nih.gov
FU Intramural Research Program of the NIEHS, National Institute of
Environmental Health Sciences/NIH
FX This research was supported by the Intramural Research Program of the
NIEHS, National Institute of Environmental Health Sciences/NIH.
NR 55
TC 0
Z9 0
U1 10
U2 10
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1750-1326
J9 MOL NEURODEGENER
JI Mol. Neurodegener.
PD NOV 24
PY 2016
VL 11
AR 70
DI 10.1186/s13024-016-0135-y
PG 12
WC Neurosciences
SC Neurosciences & Neurology
GA EC8UG
UT WOS:000388417700001
PM 27884192
ER
PT J
AU Faure, LM
Fiche, JB
Espinosa, L
Ducret, A
Anantharaman, V
Luciano, J
Lhospice, S
Islam, ST
Treguier, J
Sotes, M
Kuru, E
Van Nieuwenhze, MS
Brun, YV
Theodoly, O
Aravind, L
Nollmann, M
Mignot, T
AF Faure, Laura M.
Fiche, Jean-Bernard
Espinosa, Leon
Ducret, Adrien
Anantharaman, Vivek
Luciano, Jennifer
Lhospice, Sebastien
Islam, Salim T.
Treguier, Julie
Sotes, Melanie
Kuru, Erkin
Van Nieuwenhze, Michael S.
Brun, Yves V.
Theodoly, Olivier
Aravind, L.
Nollmann, Marcelo
Mignot, Tam
TI The mechanism of force transmission at bacterial focal adhesion
complexes
SO NATURE
LA English
DT Article
ID HIDDEN MARKOV MODEL; PROTON MOTIVE FORCE; MYXOCOCCUS-XANTHUS; GLIDING
MOTILITY; ACTIN CYTOSKELETON; ESCHERICHIA-COLI; PROTEIN; SIGNAL;
MICROSCOPY; PREDICTION
AB Various rod-shaped bacteria mysteriously glide on surfaces in the absence of appendages such as flagella or pili. In the deltaproteobacterium Myxococcus xanthus, a putative gliding motility machinery (the Agl-Glt complex) localizes to so-called focal adhesion sites (FASs) that form stationary contact points with the underlying surface. Here we show that the Agl-Glt machinery contains an inner-membrane motor complex that moves intracellularly along a right-handed helical path; when the machinery becomes stationary at FASs, the motor complex powers a left-handed rotation of the cell around its long axis. At FASs, force transmission requires cyclic interactions between the molecular motor and the adhesion proteins of the outer membrane via a periplasmic interaction platform, which presumably involves contractile activity of motor components and possible interactions with peptidoglycan. Our results provide a molecular model of bacterial gliding motility.
C1 [Faure, Laura M.; Espinosa, Leon; Ducret, Adrien; Luciano, Jennifer; Lhospice, Sebastien; Islam, Salim T.; Treguier, Julie; Sotes, Melanie; Mignot, Tam] Aix Marseille Univ, CNRS, Inst Microbiol Mediterranee, Lab Chim Bacterienne,UMR7283, F-13009 Marseille, France.
[Fiche, Jean-Bernard; Nollmann, Marcelo] Univ Montpellier, INSERM, CNRS, Ctr Biochim Struct,UMR5048,U1054, 29 Rue Navacelles, F-34090 Montpellier, France.
[Ducret, Adrien; Brun, Yves V.] Indiana Univ, Dept Biol, Bloomington, IN 47405 USA.
[Anantharaman, Vivek] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA.
[Kuru, Erkin] Indiana Univ, Interdisciplinary Biochem Program, Bloomington, IN 47405 USA.
[Van Nieuwenhze, Michael S.] Indiana Univ, Dept Chem, Bloomington, IN 47405 USA.
[Theodoly, Olivier] Aix Marseille Univ, INSERM, Adhes & Inflammat Lab, U1067,UMR7333, F-13288 Marseille, France.
RP Mignot, T (reprint author), Aix Marseille Univ, CNRS, Inst Microbiol Mediterranee, Lab Chim Bacterienne,UMR7283, F-13009 Marseille, France.; Nollmann, M (reprint author), Univ Montpellier, INSERM, CNRS, Ctr Biochim Struct,UMR5048,U1054, 29 Rue Navacelles, F-34090 Montpellier, France.
EM marcelo.nollmann@cbs.cnrs.fr; tmignot@imm.cnrs.fr
RI theodoly, olivier/P-5402-2016
FU Fondation ARC; Fondation pour la Recherche Medicale; Canadian Institutes
of Health Research; AMIDEX program of Aix-Marseille Universite; IRP
funds of the NIH; NIH [GM113172, GM51986]; European Research Council
[DOME-261105, 260787]; Bettencourt-Schueller "Coup d'elan pour la
recherche Francaise; ANR grant IBM [ANR-14-CE09-0025-01]; ANR grant
HiResBacs [ANR-15-CE11-0023]; France-BioImaging ("Investments for the
future") [ANR-10-INBS-04]; Imagine Optic
FX We thank R. Mercier for suggestions and critical reading of the
manuscript, A. Valeri for help with PCA analysis, C. Fiche for help with
image analysis and Y. Denis (IMM transcriptomics platform) for help with
quantitative PCR and M. Wartel for preliminary experiments. L.M.F. was
partially funded by Fondation ARC, L.E. was supported by the Fondation
pour la Recherche Medicale (FRM DGE2010221257), S.T.I. was supported by
a fellowship from the Canadian Institutes of Health Research and the
AMIDEX program of Aix-Marseille Universite, and A.L. and V.A. were
supported by the IRP funds of the NIH, NIH grant GM113172 to M.S.V.N.
and Y.V.B. and NIH grant GM51986 to Y.V.B. Research in the Mignot
laboratory was supported by European Research Council grant DOME-261105
and a Bettencourt-Schueller "Coup d'elan pour la recherche Francaise
2011". Research in the Nollmann laboratory was supported by ANR grants
IBM (ANR-14-CE09-0025-01), HiResBacs (ANR-15-CE11-0023), and European
Research Council grant smInsulator-260787. We acknowledge support from
France-BioImaging (ANR-10-INBS-04, "Investments for the future"), and
Imagine Optic.
NR 38
TC 1
Z9 1
U1 28
U2 28
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 24
PY 2016
VL 539
IS 7630
BP 530
EP +
DI 10.1038/nature20121
PG 20
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA ED0GI
UT WOS:000388520600037
PM 27749817
ER
PT J
AU Ried, JS
Jeff, JM
Chu, AY
Bragg-Gresham, JL
van Dongen, J
Huffman, JE
Ahluwalia, TS
Cadby, G
Eklund, N
Eriksson, J
Esko, T
Feitosa, MF
Goel, A
Gorski, M
Hayward, C
Heard-Costa, NL
Jackson, AU
Jokinen, E
Kanoni, S
Kristiansson, K
Kutalik, Z
Lahti, J
Luan, JA
Magi, R
Mahajan, A
Mangino, M
Medina-Gomez, C
Monda, KL
Nolte, IM
Perusse, L
Prokopenko, I
Qi, L
Rose, LM
Salvi, E
Smith, MT
Snieder, H
Stancakova, A
Sung, YJ
Tachmazidou, I
Teumer, A
Thorleifsson, G
van der Harst, P
Walker, RW
Wang, SR
Wild, SH
Willems, SM
Wong, A
Zhang, WH
Albrecht, E
Alves, AC
Bakker, SJL
Barlassina, C
Bartz, TM
Beilby, J
Bellis, C
Bergman, RN
Bergmann, S
Blangero, J
Bluher, M
Boerwinkle, E
Bonnycastle, LL
Bornstein, SR
Bruinenberg, M
Campbell, H
Chen, YDI
Chiang, CWK
Chines, PS
Collins, FS
Cucca, F
Cupples, LA
D'Avila, F
de Geus, EJC
Dedoussis, G
Dimitriou, M
Doring, A
Eriksson, JG
Farmaki, AE
Farrall, M
Ferreira, T
Fischer, K
Forouhi, NG
Friedrich, N
Gjesing, AP
Glorioso, N
Graff, M
Grallert, H
Grarup, N
Grassler, J
Grewal, J
Hamsten, A
Harder, MN
Hartman, CA
Hassinen, M
Hastie, N
Hattersley, AT
Havulinna, AS
Heliovaara, M
Hillege, H
Hofman, A
Holmen, O
Homuth, G
Hottenga, JJ
Hui, JN
Husemoen, LL
Hysi, PG
Isaacs, A
Ittermann, T
Jalilzadeh, S
James, AL
Jorgensen, T
Jousilahti, P
Jula, A
Justesen, JM
Justice, AE
Kahonen, M
Karaleftheri, M
Khaw, KT
Keinanen-Kiukaanniemi, SM
Kinnunen, L
Knekt, PB
Koistinen, HA
Kolcic, I
Kooner, IK
Koskinen, S
Kovacs, P
Kyriakou, T
Laitinen, T
Langenberg, C
Lewin, AM
Lichtner, P
Lindgren, CM
Lindstrom, J
Linneberg, A
Lorbeer, R
Lorentzon, M
Luben, R
Lyssenko, V
Mannisto, S
Manunta, P
Leach, IM
McArdle, WL
Mcknight, B
Mohlke, KL
Mihailov, E
Milani, L
Mills, R
Montasser, ME
Morris, AP
Muller, G
Musk, AW
Narisu, N
Ong, KK
Oostra, BA
Osmond, C
Palotie, A
Pankow, JS
Paternoster, L
Penninx, BW
Pichler, I
Pilia, MG
Polasek, O
Pramstaller, PP
Raitakari, OT
Rankinen, T
Rao, DC
Rayner, NW
Ribel-Madsen, R
Rice, TK
Richards, M
Ridker, PM
Rivadeneira, F
Ryan, KA
Sanna, S
Sarzynski, MA
Scholtens, S
Scott, RA
Sebert, S
Southam, L
Sparso, TH
Steinthorsdottir, V
Stirrups, K
Stolk, RP
Strauch, K
Stringham, HM
Swertz, MA
Swift, AJ
Tonjes, A
Tsafantakis, E
van der Most, PJ
Van Vliet-Ostaptchouk, JV
Vandenput, L
Vartiainen, E
Venturini, C
Verweij, N
Viikari, JS
Vitart, V
Vohl, MC
Vonk, JM
Waeber, G
Widen, E
Willemsen, G
Wilsgaard, T
Winkler, TW
Wright, AF
Yerges-Armstrong, LM
Zhao, JH
Zillikens, MC
Boomsma, DI
Bouchard, C
Chambers, JC
Chasman, DI
Cusi, D
Gansevoort, RT
Gieger, C
Hansen, T
Hicks, AA
Hu, F
Hveem, K
Jarvelin, MR
Kajantie, E
Kooner, JS
Kuh, D
Kuusisto, J
Laakso, M
Lakka, TA
Lehtimaki, T
Metspalu, A
Njolstad, I
Ohlsson, C
Oldehinkel, AJ
Palmer, LJ
Pedersen, O
Perola, M
Peters, A
Psaty, BM
Puolijoki, H
Rauramaa, R
Rudan, I
Salomaa, V
Schwarz, PEH
Shudiner, AR
Smit, JH
Sorensen, TIA
Spector, TD
Stefansson, K
Stumvoll, M
Tremblay, A
Tuomilehto, J
Uitterlinden, AG
Uusitupa, M
Volker, U
Vollenweider, P
Wareham, NJ
Watkins, H
Wilson, JF
Zeggini, E
Abecasis, GR
Boehnke, M
Borecki, IB
Deloukas, P
van Duijn, CM
Fox, C
Groop, LC
Heid, IM
Hunter, DJ
Kaplan, RC
McCarthy, MI
North, KE
O'Connell, JR
Schlessinger, D
Thorsteinsdottir, U
Strachan, DP
Frayling, T
Hirschhorn, JN
Muller-Nurasyid, M
Loos, RJF
AF Ried, Janina S.
Jeff, Janina M.
Chu, Audrey Y.
Bragg-Gresham, Jennifer L.
van Dongen, Jenny
Huffman, Jennifer E.
Ahluwalia, Tarunveer S.
Cadby, Gemma
Eklund, Niina
Eriksson, Joel
Esko, Tonu
Feitosa, Mary F.
Goel, Anuj
Gorski, Mathias
Hayward, Caroline
Heard-Costa, Nancy L.
Jackson, Anne U.
Jokinen, Eero
Kanoni, Stavroula
Kristiansson, Kati
Kutalik, Zoltan
Lahti, Jari
Luan, Jian'an
Maegi, Reedik
Mahajan, Anubha
Mangino, Massimo
Medina-Gomez, Carolina
Monda, Keri L.
Nolte, Ilja M.
Perusse, Louis
Prokopenko, Inga
Qi, Lu
Rose, Lynda M.
Salvi, Erika
Smith, Megan T.
Snieder, Harold
Stancakova, Alena
Sung, Yun Ju
Tachmazidou, Ioanna
Teumer, Alexander
Thorleifsson, Gudmar
van der Harst, Pim
Walker, Ryan W.
Wang, Sophie R.
Wild, Sarah H.
Willems, Sara M.
Wong, Andrew
Zhang, Weihua
Albrecht, Eva
Alves, Alexessander Couto
Bakker, Stephan J. L.
Barlassina, Cristina
Bartz, Traci M.
Beilby, John
Bellis, Claire
Bergman, Richard N.
Bergmann, Sven
Blangero, John
Blueher, Matthias
Boerwinkle, Eric
Bonnycastle, Lori L.
Bornstein, Stefan R.
Bruinenberg, Marcel
Campbell, Harry
Chen, Yii-Der Ida
Chiang, Charleston W. K.
Chines, Peter S.
Collins, Francis S.
Cucca, Fracensco
Cupples, L. Adrienne
D'Avila, Francesca
de Geus, Eco J. C.
Dedoussis, George
Dimitriou, Maria
Doering, Angela
Eriksson, Johan G.
Farmaki, Aliki-Eleni
Farrall, Martin
Ferreira, Teresa
Fischer, Krista
Forouhi, Nita G.
Friedrich, Nele
Gjesing, Anette Prior
Glorioso, Nicola
Graff, Mariaelisa
Grallert, Harald
Grarup, Niels
Graessler, Juergen
Grewal, Jagvir
Hamsten, Anders
Harder, Marie Neergaard
Hartman, Catharina A.
Hassinen, Maija
Hastie, Nicholas
Hattersley, Andrew Tym
Havulinna, Aki S.
Heliovaara, Markku
Hillege, Hans
Hofman, Albert
Holmen, Oddgeir
Homuth, Georg
Hottenga, Jouke-Jan
Hui, Jennie
Husemoen, Lise Lotte
Hysi, Pirro G.
Isaacs, Aaron
Ittermann, Till
Jalilzadeh, Shapour
James, Alan L.
Jorgensen, Torben
Jousilahti, Pekka
Jula, Antti
Justesen, Johanne Marie
Justice, Anne E.
Kahonen, Mika
Karaleftheri, Maria
Khaw, Kay Tee
Keinanen-Kiukaanniemi, Sirkka M.
Kinnunen, Leena
Knekt, Paul B.
Koistinen, Heikki A.
Kolcic, Ivana
Kooner, Ishminder K.
Koskinen, Seppo
Kovacs, Peter
Kyriakou, Theodosios
Laitinen, Tomi
Langenberg, Claudia
Lewin, Alexandra M.
Lichtner, Peter
Lindgren, Cecilia M.
Lindstrom, Jaana
Linneberg, Allan
Lorbeer, Roberto
Lorentzon, Mattias
Luben, Robert
Lyssenko, Valeriya
Mannisto, Satu
Manunta, Paolo
Leach, Irene Mateo
McArdle, Wendy L.
Mcknight, Barbara
Mohlke, Karen L.
Mihailov, Evelin
Milani, Lili
Mills, Rebecca
Montasser, May E.
Morris, Andrew P.
Mueller, Gabriele
Musk, Arthur W.
Narisu, Narisu
Ong, Ken K.
Oostra, Ben A.
Osmond, Clive
Palotie, Aarno
Pankow, James S.
Paternoster, Lavinia
Penninx, Brenda W.
Pichler, Irene
Pilia, Maria G.
Polasek, Ozren
Pramstaller, Peter P.
Raitakari, Olli T.
Rankinen, Tuomo
Rao, D. C.
Rayner, Nigel W.
Ribel-Madsen, Rasmus
Rice, Treva K.
Richards, Marcus
Ridker, Paul M.
Rivadeneira, Fernando
Ryan, Kathy A.
Sanna, Serena
Sarzynski, Mark A.
Scholtens, Salome
Scott, Robert A.
Sebert, Sylvain
Southam, Lorraine
Sparso, Thomas Hempel
Steinthorsdottir, Valgerdur
Stirrups, Kathleen
Stolk, Ronald P.
Strauch, Konstantin
Stringham, Heather M.
Swertz, Morris A.
Swift, Amy J.
Toenjes, Anke
Tsafantakis, Emmanouil
van der Most, Peter J.
Van Vliet-Ostaptchouk, Jana V.
Vandenput, Liesbeth
Vartiainen, Erkki
Venturini, Cristina
Verweij, Niek
Viikari, Jorma S.
Vitart, Veronique
Vohl, Marie-Claude
Vonk, Judith M.
Waeber, Gerard
Widen, Elisabeth
Willemsen, Gonneke
Wilsgaard, Tom
Winkler, Thomas W.
Wright, Alan F.
Yerges-Armstrong, Laura M.
Zhao, Jing Hua
Zillikens, M. Carola
Boomsma, Dorret I.
Bouchard, Claude
Chambers, John C.
Chasman, Daniel I.
Cusi, Daniele
Gansevoort, Ron T.
Gieger, Christian
Hansen, Torben
Hicks, Andrew A.
Hu, Frank
Hveem, Kristian
Jarvelin, Marjo-Riitta
Kajantie, Eero
Kooner, Jaspal S.
Kuh, Diana
Kuusisto, Johanna
Laakso, Markku
Lakka, Timo A.
Lehtimaeki, Terho
Metspalu, Andres
Njolstad, Inger
Ohlsson, Claes
Oldehinkel, Albertine J.
Palmer, Lyle J.
Pedersen, Oluf
Perola, Markus
Peters, Annette
Psaty, Bruce M.
Puolijoki, Hannu
Rauramaa, Rainer
Rudan, Igor
Salomaa, Veikko
Schwarz, Peter E. H.
Shudiner, Alan R.
Smit, Jan H.
Sorensen, Thorkild I. A.
Spector, Timothy D.
Stefansson, Kari
Stumvoll, Michael
Tremblay, Angelo
Tuomilehto, Jaakko
Uitterlinden, Andre G.
Uusitupa, Matti
Voelker, Uwe
Vollenweider, Peter
Wareham, Nicholas J.
Watkins, Hugh
Wilson, James F.
Zeggini, Eleftheria
Abecasis, Goncalo R.
Boehnke, Michael
Borecki, Ingrid B.
Deloukas, Panos
van Duijn, Cornelia M.
Fox, Caroline
Groop, Leif C.
Heid, Iris M.
Hunter, David J.
Kaplan, Robert C.
McCarthy, Mark I.
North, Kari E.
O'Connell, Jeffrey R.
Schlessinger, David
Thorsteinsdottir, Unnur
Strachan, David P.
Frayling, Timothy
Hirschhorn, Joel N.
Mueller-Nurasyid, Martina
Loos, Ruth J. F.
TI A principal component meta-analysis on multiple anthropometric traits
identifies novel loci for body shape
SO NATURE COMMUNICATIONS
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; DIET-INDUCED OBESITY; MASS INDEX; DISEASE
ASSOCIATIONS; FAT DISTRIBUTION; EARLY-ONSET; HIP RATIO; RESOURCE;
BIOLOGY; HEIGHT
AB Large consortia have revealed hundreds of genetic loci associated with anthropometric traits, one trait at a time. We examined whether genetic variants affect body shape as a composite phenotype that is represented by a combination of anthropometric traits. We developed an approach that calculates averaged PCs (AvPCs) representing body shape derived from six anthropometric traits (body mass index, height, weight, waist and hip circumference, waist-to-hip ratio). The first four AvPCs explain >99% of the variability, are heritable, and associate with cardiometabolic outcomes. We performed genome-wide association analyses for each body shape composite phenotype across 65 studies and meta-analysed summary statistics. We identify six novel loci: LEMD2 and CD47 for AvPC1, RPS6KA5/C14orf159 and GANAB for AvPC3, and ARL15 and ANP32 for AvPC4. Our findings highlight the value of using multiple traits to define complex phenotypes for discovery, which are not captured by single-trait analyses, and may shed light onto new pathways.
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[Jeff, Janina M.; Walker, Ryan W.; Loos, Ruth J. F.] Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA.
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[Doering, Angela; Grallert, Harald; Gieger, Christian; Peters, Annette] Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Epidemiol 2, D-85764 Neuherberg, Germany.
[Eriksson, Johan G.; Kajantie, Eero] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, FI-00271 Helsinki, Finland.
[Eriksson, Johan G.] Univ Helsinki, Dept Gen Practice & Primary Hlth Care, FI-00014 Helsinki, Finland.
[Friedrich, Nele] Univ Med Greifswald, Inst Clin Chem & Lab Med, D-17475 Greifswald, Germany.
[Glorioso, Nicola] AOU Univ Sassari, Hypertens & Related Dis Ctr, I-7100 Sassari, Italy.
[Grallert, Harald] German Ctr Diabet Res DZD, D-85764 Neuherberg, Germany.
[Grallert, Harald; Gieger, Christian; Peters, Annette] Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Res Unit Mol Epidemiol, D-85764 Neuherberg, Germany.
[Graessler, Juergen] Tech Univ, Dept Med 3, Pathobiochem, D-01307 Dresden, Germany.
[Hamsten, Anders] Karolinska Inst, Dept Med, Stockholm, Sweden.
[Hamsten, Anders] Karolinska Inst, Atherosclerosis Res Unit, Dept Med Solna, S-17176 Stockholm, Sweden.
[Hamsten, Anders] Karolinska Univ Hosp, Ctr Mol Med, S-17176 Stockholm, Sweden.
[Hartman, Catharina A.; Oldehinkel, Albertine J.] Univ Groningen, Univ Med Ctr Groningen, Interdisciplinary Ctr Psychopathol & Emot Regulat, NL-9700 RB Groningen, Netherlands.
[Hassinen, Maija; Lakka, Timo A.; Rauramaa, Rainer] Kuopio Res Inst Exercise Med, Kuopio 70100, Finland.
[Hattersley, Andrew Tym] Univ Exeter, Inst Biomed & Clin Sci, Barrack Rd, Exeter EX2 5DW, Devon, England.
[Holmen, Oddgeir; Hveem, Kristian] Norwegian Univ Sci & Technol, Dept Publ Hlth & Gen Practice, N-7489 Trondheim, Norway.
[Hui, Jennie] Univ Western Australia, Sch Populat Hlth, Nedlands, WA 6009, Australia.
[Husemoen, Lise Lotte; Linneberg, Allan] Glostrup Cty Hosp, Res Ctr Prevent & Hlth, DK-2600 Glostrup, Denmark.
[James, Alan L.] Sir Charles Gairdner Hosp, Dept Pulm Physiol & Sleep Med, Nedlands, WA 6009, Australia.
[Jorgensen, Torben; Linneberg, Allan] Univ Copenhagen, Fac Hlth & Med Sci, Dept Clin Med, DK-2200 Copenhagen, Denmark.
[Jorgensen, Torben] Aalborg Univ, Fac Med, DK-9220 Aalborg, Denmark.
[Jorgensen, Torben] Capital Region Denmark, Res Ctr Prevent & Hlth, DK-2600 Glostrup, Denmark.
[Kahonen, Mika] Tampere Univ Hosp, Dept Clin Physiol, FI-33521 Tampere, Finland.
[Kahonen, Mika] Univ Tampere, Sch Med, Dept Clin Physiol, FI-33014 Tampere, Finland.
[Karaleftheri, Maria] Echinos Med Ctr, Echinos 67300, Greece.
[Khaw, Kay Tee] Addenbrookes Hosp, Clin Gerontol Unit, Box 251,Hills Rd, Cambridge CB2 2QQ, England.
[Keinanen-Kiukaanniemi, Sirkka M.] Univ Oulu, Fac Med, Inst Hlth Sci, FI-90014 Oulu, Finland.
[Keinanen-Kiukaanniemi, Sirkka M.] Oulu Univ Hosp, Unit Gen Practice, FI-90029 Oulu, Finland.
[Kinnunen, Leena; Koistinen, Heikki A.] Natl Inst Hlth & Welf, FI-00271 Helsinki, Finland.
[Koistinen, Heikki A.] Univ Helsinki, Abdominal Ctr Endocrinol, Dept Med, Helsinki 00290, Finland.
[Koistinen, Heikki A.] Minerva Fdn, Helsinki 00290, Finland.
[Kolcic, Ivana; Polasek, Ozren] Univ Split, Fac Med, Dept Publ Hlth, Split 21000, Croatia.
[Laitinen, Tomi] Kuopio Univ Hosp, Kuopio 70029, Finland.
[Laitinen, Tomi] Univ Eastern Finland, Dept Clin Physiol & Nucl Med, FI-70211 Kuopio, Finland.
[Langenberg, Claudia] UCL, Dept Epidemiol & Publ Hlth, London WC1E 6BT, England.
[Lichtner, Peter] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Human Genet, D-85764 Neuherberg, Germany.
[Lindgren, Cecilia M.] Univ Oxford, Big Data Inst, Oxford OX3 7LJ, England.
[Linneberg, Allan] Rigshosp, Dept Clin Expt Res, DK-2600 Glostrup, Denmark.
[Luben, Robert] Strangeways Res Lab Worts Causeway, Cambridge CB1 8RN, England.
[Lyssenko, Valeriya; Groop, Leif C.] Lund Univ, Diabet Ctr, S-22100 Malmo, Sweden.
[Lyssenko, Valeriya; Groop, Leif C.] Lund Univ, Dept Clin Sci, Diabet & Endocrinol Unit, S-22100 Malmo, Sweden.
[Manunta, Paolo] Univ Vita Salute San Raffaele, Chair Nephrol, I-20139 Milan, Italy.
[Manunta, Paolo] IRCCS San Raffaele Sci Inst, Genom Renal Dis & Hypertens Unit, I-20139 Milan, Italy.
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[Paternoster, Lavinia] Univ Bristol, Sch Social & Community Med, MRC Integrat Epidemiol Unit, Bristol BS8 1TH, Avon, England.
[Penninx, Brenda W.; Smit, Jan H.] Vrije Univ Amsterdam, Med Ctr, Dept Psychiat, AJ Ernstr 1887, NL-1081 HL Amsterdam, Netherlands.
[Penninx, Brenda W.; Smit, Jan H.] Vrije Univ Amsterdam, Med Ctr, EMGO Inst Hlth & Care Res, AJ Ernstr 1887, NL-1081 HL Amsterdam, Netherlands.
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[Pilia, Maria G.; Sanna, Serena] CNR, Ist Ric Genet & Biomed, I-9042 Monserrato, Italy.
[Pramstaller, Peter P.] Univ Lubeck, Dept Neurol, D-23562 Lubeck, Germany.
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[Raitakari, Olli T.] Turku Univ Hosp, Dept Clin Physiol & Nucl Med, FI-20521 Turku, Finland.
[Raitakari, Olli T.] Univ Turku, Res Ctr Appl & Prevent Cardiovasc Med, FI-20520 Turku, Finland.
[Rankinen, Tuomo; Sarzynski, Mark A.; Bouchard, Claude] Pennington Biomed Res Ctr, Human Genom Lab, Baton Rouge, LA 70808 USA.
[Rice, Treva K.] Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA.
[Rayner, Nigel W.; Deloukas, Panos] Wellcome Trust Sanger Inst, Human Genet, Hinxton CB10 1HH, England.
[Ridker, Paul M.; Chasman, Daniel I.; Fox, Caroline] Harvard Med Sch, Boston, MA 02115 USA.
[Sebert, Sylvain; Jarvelin, Marjo-Riitta] Univ Oulu, Bioctr Oulu, FI-90014 Oulu, Finland.
[Sebert, Sylvain] Univ Oulu, Ctr Life Course Hlth Res, FI-90014 Oulu, Finland.
[Strauch, Konstantin; Mueller-Nurasyid, Martina] Ludwig Maximilians Univ Munchen, Inst Med Informat Biometry & Epidemiol, Chair Genet Epidemiol, D-81377 Munich, Germany.
[Tsafantakis, Emmanouil] Anogia Med Ctr, Anogia 74051, Greece.
[Van Vliet-Ostaptchouk, Jana V.] Univ Groningen, Univ Med Ctr Groningen, Dept Endocrinol, NL-9700 RB Groningen, Netherlands.
[Venturini, Cristina] UCL, Inst Ophthalmol, London EC1V 9EL, England.
[Viikari, Jorma S.] Univ Turku, Dept Med, FI 20521 Turku, FI-20521 Turku, Finland.
[Viikari, Jorma S.] Turku Univ Hosp, Div Med, Turku, Finland.
[Vohl, Marie-Claude] Univ Laval, Sch Nutr, Quebec City, PQ G1V 0A6, Canada.
[Waeber, Gerard; Vollenweider, Peter] Univ Hosp Lausanne CHUV, Dept Internal Med, CH-1011 Lausanne, Switzerland.
[Waeber, Gerard; Vollenweider, Peter] Univ Lausanne, CH-1011 Lausanne, Switzerland.
[Wilsgaard, Tom; Njolstad, Inger] Univ Tromso, Fac Hlth Sci, Dept Community Med, N-9037 Tromso, Norway.
[Chambers, John C.; Kooner, Jaspal S.] Imperial Coll Healthcare NHS Trust, London W12 0HS, England.
[Hansen, Torben] Univ Southern Denmark, Fac Hlth Sci, DK-5000 Odense, Denmark.
Oulu Univ Hosp, Unit Primary Care, Oys Oulu 90029, Finland.
[Jarvelin, Marjo-Riitta] Imperial Coll London, Sch Publ Hlth, MRC PHE Ctr Environm & Hlth, Dept Epidemiol & Biostat, London W12 0NN, England.
[Jarvelin, Marjo-Riitta] Univ Oulu, Ctr Life Course Epidemiol, Fac Med, POB 5000, FI-90014 Oulu, Finland.
[Kajantie, Eero] Helsinki Univ Hosp, Childrens Hosp, FI-00029 Helsinki, Finland.
[Kajantie, Eero] Univ Helsinki, FI-00029 Helsinki, Finland.
[Kajantie, Eero] Oulu Univ Hosp, MRC Oulu, Dept Obstet & Gynecol, FI-90029 Oulu, Finland.
[Kajantie, Eero] Univ Oulu, FI-90029 Oulu, Finland.
[Kooner, Jaspal S.] Imperial Coll London, Natl Heart & Lung Inst, London W12 0NN, England.
[Lakka, Timo A.] Univ Eastern Finland, Inst Biomed, Dept Physiol, Kuopio Campus, Kuopio 70210, Finland.
[Lehtimaeki, Terho] Univ Tampere, Sch Med, Dept Clin Chem, FI-33014 Tampere, Finland.
[Lehtimaeki, Terho] Univ Tampere, Fimlab Labs, Dept Clin Chem, FI-33520 Tampere, Finland.
[Lehtimaeki, Terho] Univ Tampere, Sch Med, FI-33520 Tampere, Finland.
[Njolstad, Inger] Univ Tromso, Fac Hlth Sci, Dept Clin Med, N-9037 Tromso, Norway.
[Palmer, Lyle J.] Univ Adelaide, Sch Publ Hlth, Adelaide, SA 5005, Australia.
[Palmer, Lyle J.] Univ Adelaide, Robinson Res Inst, Adelaide, SA 5005, Australia.
[Peters, Annette; Mueller-Nurasyid, Martina] DZHK German Ctr Cardiovasc Res, Partnersite Munich Heart Alliance, D-80802 Munich, Germany.
[Tuomilehto, Jaakko] Univ Washington, Dept Med, Seattle, WA 98101 USA.
[Psaty, Bruce M.] Univ Washington, Dept Epidemiol, Washington, DC 98101 USA.
[Psaty, Bruce M.] Univ Washington, Dept Hlth Serv, Washington, DC 98101 USA.
[Psaty, Bruce M.] Grp Hlth Res Inst, Grp Hlth Cooperat, Washington, DC 98101 USA.
[Puolijoki, Hannu] South Ostrobothnia Cent Hosp, FI-60220 Seinajoki, Finland.
[Rauramaa, Rainer] Kuopio Univ Hosp, Dept Clin Physiol & Nucl Med, Kuopio 70211, Finland.
[Schwarz, Peter E. H.] German Ctr Diabet Res DZD, Paul Langerhans Inst Dresden, D-01307 Dresden, Germany.
[Shudiner, Alan R.] Vet Adm Med Ctr, Geriatr Res & Educ Clin Ctr, Baltimore, MD 21042 USA.
[Sorensen, Thorkild I. A.] Univ Bristol, Sch Social & Community Med, MRC Integrat Epidemiol Unit, Bristol BS8 2BN, Avon, England.
[Sorensen, Thorkild I. A.] Bispebjerg & Frederiksberg Hosp, Inst Prevent Med, DK-2000 Frederiksberg, Denmark.
[Stefansson, Kari; Thorsteinsdottir, Unnur] Univ Iceland, Fac Med, IS-101 Reykjavik, Iceland.
[Tuomilehto, Jaakko] Natl Inst Hlth & Welf, Diabet Prevent Unit, FI-00271 Helsinki, Finland.
[Tuomilehto, Jaakko] Danube Univ Krems, Ctr Vasc Prevent, A-3500 Krems, Austria.
[Tuomilehto, Jaakko] King Abdulaziz Univ, Diabet Res Grp, Jeddah 21589, Saudi Arabia.
[Uusitupa, Matti] Univ Eastern Finland, Dept Publ Hlth & Clin Nutr, Kuopio 70211, Finland.
[Uusitupa, Matti] Kuopio Univ Hosp, Res Unit, Kuopio 70029, Finland.
[Voelker, Uwe] DZHK German Ctr Cardiovasc Res, Partner Site Greifswald, D-17475 Greifswald, Germany.
[Deloukas, Panos] King Abdulaziz Univ, PACER HD, Jeddah 21589, Saudi Arabia.
[van Duijn, Cornelia M.] Ctr Med Syst Biol, NL-2300 Leiden, Netherlands.
[Groop, Leif C.] Univ Helsinki, Finnish Inst Mol Med FIMM, Helsinki 00014, Finland.
[Heid, Iris M.] Helmholtz Zentrum Munchen, Inst Genet Epidemiol, D-85764 Neuherberg, Germany.
[Hunter, David J.] Harvard Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Kaplan, Robert C.] Albert Einstein Coll Med, Dept Epidemiol & Popualt Hlth, Bronx, NY 10461 USA.
[McCarthy, Mark I.] Oxford NIHR Biomed Res Ctr, Oxford OX3 7LJ, England.
[North, Kari E.] Univ North Carolina Chapel Hill, Dept Epidemiol, Carolina Ctr Genome Sci, Chapel Hill, NC 27599 USA.
[Schlessinger, David] NIA, NIH, Bethesda, MD 20892 USA.
[Strachan, David P.] St Georges Univ London, Populat Hlth Res Inst, London SW17 0RE, England.
[Frayling, Timothy] Univ Exeter, Sch Med, Genet Complex Traits, Exeter EX1 2LU, Devon, England.
[Hirschhorn, Joel N.] Broad Inst, Metab Initiat, Cambridge, MA 02142 USA.
[Mueller-Nurasyid, Martina] Ludwig Maximilians Univ Munchen, Univ Hosp Grosshadern, Dept Med 1, D-81377 Munich, Germany.
[Loos, Ruth J. F.] Icahn Sch Med Mt Sinai, Genet Obes & Related Metab Traits Program, New York, NY 10029 USA.
[Loos, Ruth J. F.] Icahn Sch Med Mt Sinai, Mindich Child Hlth & Dev Inst, New York, NY 10029 USA.
RP Muller-Nurasyid, M (reprint author), Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Genet Epidemiol, D-85764 Neuherberg, Germany.; Loos, RJF (reprint author), Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA.; Loos, RJF (reprint author), Univ Cambridge, Inst Metab Sci, Sch Clin Med, MRC Epidemiol Unit, Cambridge Biomed Campus, Cambridge CB2 0QQ, England.; Loos, RJF (reprint author), Icahn Sch Med Mt Sinai, Dept Prevent Med, New York, NY 10029 USA.; Muller-Nurasyid, M (reprint author), Ludwig Maximilians Univ Munchen, Inst Med Informat Biometry & Epidemiol, Chair Genet Epidemiol, D-81377 Munich, Germany.; Muller-Nurasyid, M (reprint author), DZHK German Ctr Cardiovasc Res, Partnersite Munich Heart Alliance, D-80802 Munich, Germany.; Muller-Nurasyid, M (reprint author), Ludwig Maximilians Univ Munchen, Univ Hosp Grosshadern, Dept Med 1, D-81377 Munich, Germany.; Loos, RJF (reprint author), Icahn Sch Med Mt Sinai, Genet Obes & Related Metab Traits Program, New York, NY 10029 USA.; Loos, RJF (reprint author), Icahn Sch Med Mt Sinai, Mindich Child Hlth & Dev Inst, New York, NY 10029 USA.
EM ruth.loos@mssm.edu
RI Sarzynski, Mark/A-9798-2014; Hicks, Andrew/E-9518-2017; Justesen,
Johanne Marie/L-6023-2015; Wong, Andrew/M-8899-2016; Verweij,
Niek/A-4499-2017; Colaus, PsyColaus/K-6607-2013; Grallert,
Harald/B-3424-2013; Grarup, Niels/K-2807-2015; Bouchard,
Claude/A-7637-2009; Palmer, Lyle/K-3196-2014; Polasek,
Ozren/B-6002-2011; Kolcic, Ivana/E-2713-2017; Feitosa, Mary/K-8044-2012;
OI Hicks, Andrew/0000-0001-6320-0411; Justesen, Johanne
Marie/0000-0002-0484-8522; Wong, Andrew/0000-0003-2079-4779; Grarup,
Niels/0000-0001-5526-1070; Palmer, Lyle/0000-0002-1628-3055; Polasek,
Ozren/0000-0002-5765-1862; Kolcic, Ivana/0000-0001-7918-6052; Feitosa,
Mary/0000-0002-0933-2410; Linneberg, Allan/0000-0002-0994-0184; Peters,
Annette/0000-0001-6645-0985; Lahti, Jari/0000-0002-4310-5297; Havulinna,
Aki/0000-0002-4787-8959; Forouhi, Nita/0000-0002-5041-248X; Salvi,
Erika/0000-0002-2724-2291; Vandenput, Liesbeth/0000-0002-1712-6131;
Jorgensen, Torben/0000-0001-9453-2830; Medina-Gomez,
Carolina/0000-0001-7999-5538; Pankow, James/0000-0001-7076-483X; de
Geus, Eco/0000-0001-6022-2666
FU Medical Research Council [G0601261, MC_PC_U127561128, MC_UP_A620_1016,
MC_UU_12011/3, MC_UU_12015/1, MC_UU_12019/1, MR/J012165/1]; NCATS NIH
HHS [UL1 TR000124]; NHLBI NIH HHS [R01 HL117626]; NICHD NIH HHS [P2C
HD050924]; NIDDK NIH HHS [P30 DK020541, P30 DK063491, U01 DK062370]
NR 48
TC 0
Z9 0
U1 10
U2 10
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2041-1723
J9 NAT COMMUN
JI Nat. Commun.
PD NOV 23
PY 2016
VL 7
AR 13357
DI 10.1038/ncomms13357
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EC7LH
UT WOS:000388319700001
PM 27876822
ER
PT J
AU Chia, CW
Shardell, M
Tanaka, T
Liu, DD
Gravenstein, KS
Simonsick, EM
Egan, JM
Ferrucci, L
AF Chia, Chee W.
Shardell, Michelle
Tanaka, Toshiko
Liu, David D.
Gravenstein, Kristofer S.
Simonsick, Eleanor M.
Egan, Josephine M.
Ferrucci, Luigi
TI Chronic Low-Calorie Sweetener Use and Risk of Abdominal Obesity among
Older Adults: A Cohort Study
SO PLOS ONE
LA English
DT Article
ID RANDOMIZED CLINICAL-TRIAL; DIET SODA INTAKE; WAIST CIRCUMFERENCE;
METABOLIC SYNDROME; BODY-WEIGHT; ARTIFICIAL SWEETENERS; BEVERAGE
CONSUMPTION; CARDIOVASCULAR RISK; CAUSAL INFERENCE; FOOD-INTAKE
AB Introduction
Low-calorie sweetener use for weight control has come under increasing scrutiny as obesity, especially abdominal obesity, remain entrenched despite substantial low-calorie sweetener use. We evaluated whether chronic low-calorie sweetener use is a risk factor for abdominal obesity.
Participants and Methods
We used 8268 anthropometric measurements and 3096 food diary records with detailed information on low-calorie sweetener consumption in all food products, from 1454 participants (741 men, 713 women) in the Baltimore Longitudinal Study of Aging collected from 1984 to 2012 with median follow-up of 10 years (range: 0-28 years). At baseline, 785 were low-calorie sweetener non-users (51.7% men) and 669 participants were low-calorie sweetener users (50.1% men). Time-varying low-calorie sweetener use was operationalized as the proportion of visits since baseline at which low-calorie sweetener use was reported. We used marginal structural models to determine the association between baseline and timevarying low-calorie sweetener use with longitudinal outcomes D body mass index, waist circumference, obesity and abdominal obesity D with outcome status assessed at the visit following low-calorie sweetener ascertainment to minimize the potential for reverse causality. All models were adjusted for year of visit, age, sex, age by sex interaction, race, current smoking status, dietary intake (caffeine, fructose, protein, carbohydrate, and fat), physical activity, diabetes status, and Dietary Approaches to Stop Hypertension score as confounders.
Results
With median follow-up of 10 years, low-calorie sweetener users had 0.80 kg/m(2) higher body mass index (95% confidence interval [CI], 0.17-1.44), 2.6 cm larger waist circumference (95% CI, 0.71 +/- 4.39), 36.7% higher prevalence (prevalence ratio = 1.37; 95% CI, 1.10 -1.69) and 53% higher incidence (hazard ratio = 1.53; 95% CI 1.10 - 2.12) of abdominal obesity than low-calorie sweetener non-users.
Conclusions
Low-calorie sweetener use is independently associated with heavier relative weight, a larger waist, and a higher prevalence and incidence of abdominal obesity suggesting that low-calorie sweetener use may not be an effective means of weight control.
C1 [Chia, Chee W.; Shardell, Michelle; Tanaka, Toshiko; Liu, David D.; Gravenstein, Kristofer S.; Simonsick, Eleanor M.; Egan, Josephine M.; Ferrucci, Luigi] NIA, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
RP Chia, CW (reprint author), NIA, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
EM chiac@mail.nih.gov
FU Intramural Research Program of the National Institutes of Health,
National Institute on Aging, Baltimore, Maryland, USA
FX This research was supported by the Intramural Research Program of the
National Institutes of Health, National Institute on Aging, Baltimore,
Maryland, USA. The funders had no role in study design, data collection
and analysis, decision to publish, or preparation of the manuscript.;
This research was supported by the Intramural Research Program of the
National Institutes of Health, National Institute on Aging, Baltimore,
Maryland, USA.
NR 45
TC 0
Z9 0
U1 19
U2 19
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 NOV 23
PY 2016
VL 11
IS 11
AR e0167241
DI 10.1371/journal.pone.0167241
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA ED5KB
UT WOS:000388889500081
PM 27880832
ER
PT J
AU Swaminathan, S
Qiu, J
Rupert, AW
Hu, ZH
Higgins, J
Dewar, RL
Stevens, R
Rehm, CA
Metcalf, JA
Sherman, BT
Baseler, MW
Lane, HC
Imamichi, T
AF Swaminathan, Sanjay
Qiu, Ju
Rupert, Adam W.
Hu, Zonghui
Higgins, Jeanette
Dewar, Robin L.
Stevens, Randy
Rehm, Catherine A.
Metcalf, Julia A.
Sherman, Brad T.
Baseler, Michael W.
Lane, H. Clifford
Imamichi, Tomozumi
TI Interleukin-15 (IL-15) Strongly Correlates with Increasing HIV-1 Viremia
and Markers of Inflammation
SO PLOS ONE
LA English
DT Article
ID T-CELLS; INFECTION
AB Objective
IL-15 has been postulated to play an important role in HIV-1 infection, yet there are conflicting reports regarding its expression levels in these patients. We sought to measure the level of IL-15 in a large, well characterised cohort of HIV-1 infected patients and correlate this with well known markers of inflammation, including CRP, D-dimer, sCD163 and sCD14.
Design and Methods
IL-15 levels were measured in 501 people (460 patients with HIV-1 infection and 41 uninfected controls). The HIV-1 infected patients were divided into 4 groups based on viral load: < 50 copies/ml, 51 - 10,000 copies/ml, 10,001 - 100,000 copies/ml and > 100,000 copies/ml. The Mann Whitney test (non-parametric) was used to identify significant relationships between different patient groups.
Results
IL-15 levels were significantly higher in patients with viral loads > 100,000 copies/ml (3.02 +/- 1.53 pg/ml) compared to both uninfected controls (1.69 +/- 0.37 pg/ml, p< 0.001) or patients with a viral load < 50 copies/ml (1.59 +/- 0.40 pg/ml (p< 0.001). There was a significant correlation between HIV-1 viremia and IL-15 levels (Spearman r = 0.54, p< 0.001) and between CD4+ T cell counts and IL-15 levels (Spearman r =-0.56, p< 0.001).
Conclusions
IL-15 levels are significantly elevated in HIV-1 infected patients with viral loads > 100,000 copies/ml compared to uninfected controls, with a significant direct correlation noted between IL-15 and HIV-1 viremia and an inverse correlation between IL-15 levels and CD4+ T cell counts. These data support a potential role for IL-15 in the pathogenesis of HIV-associated immune activation.
C1 [Swaminathan, Sanjay; Qiu, Ju; Rupert, Adam W.; Higgins, Jeanette; Dewar, Robin L.; Stevens, Randy; Sherman, Brad T.; Baseler, Michael W.; Imamichi, Tomozumi] Frederick Natl Lab Canc Res, Appl & Dev Res Directorate, Leidos Biomed Res Inc, Frederick, MD 21702 USA.
[Swaminathan, Sanjay] Western Sydney Local Hlth Dist, Dept Clin Immunol, Sydney, NSW, Australia.
[Swaminathan, Sanjay] Univ Sydney, Sydney Med Sch, Sydney, NSW, Australia.
[Swaminathan, Sanjay] Univ Western Sydney, Sch Med, Sydney, NSW, Australia.
[Hu, Zonghui] NIAID, Biostat Res Branch, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Rehm, Catherine A.; Lane, H. Clifford] NIAID, Immunoregulat Lab, NIH, Bldg 10, Bethesda, MD 20892 USA.
[Metcalf, Julia A.; Lane, H. Clifford] NIAID, Div Clin Res, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
RP Imamichi, T (reprint author), Frederick Natl Lab Canc Res, Appl & Dev Res Directorate, Leidos Biomed Res Inc, Frederick, MD 21702 USA.
EM timamichi@mail.nih.gov
FU National Cancer Institute, National Institutes of Health
[HHSN261200800001E]; National Institute of Allergy and Infectious
Disease
FX This project has been funded in whole or in part with federal funds from
the National Cancer Institute, National Institutes of Health, under
Contract No. HHSN261200800001E. 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 National Institute of Allergy
and Infectious Disease.
NR 13
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Z9 0
U1 0
U2 0
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD NOV 23
PY 2016
VL 11
IS 11
AR e0167091
DI 10.1371/journal.pone.0167091
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA ED5KB
UT WOS:000388889500066
PM 27880829
ER
PT J
AU Yang, BY
Shebl, FM
Sternberg, LR
Warner, AC
Kleiner, DE
Edelman, DC
Gomez, A
Dagnall, CL
Hicks, BD
Altekruse, SF
Hernandez, BY
Lynch, CF
Meltzer, PS
McGlynn, KA
AF Yang, Baiyu
Shebl, Fatma M.
Sternberg, Lawrence R.
Warner, Andrew C.
Kleiner, David E.
Edelman, Daniel C.
Gomez, Allison
Dagnall, Casey L.
Hicks, Belynda D.
Altekruse, Sean F.
Hernandez, Brenda Y.
Lynch, Charles F.
Meltzer, Paul S.
McGlynn, Katherine A.
TI Telomere Length and Survival of Patients with Hepatocellular Carcinoma
in the United States
SO PLOS ONE
LA English
DT Article
ID CHRONIC LIVER-DISEASE; HEPATITIS-VIRUS; TRANSARTERIAL CHEMOEMBOLIZATION;
QUANTITATIVE PCR; LONG TELOMERES; CANCER; HEPATOCARCINOGENESIS; TISSUES;
REACTIVATION; MAINTENANCE
AB Background
Telomere shortening is an important molecular event in hepatocellular carcinoma (HCC) initiation; however, its role in HCC progression and prognosis is less clear. Our study aimed to examine the association of telomere length with survival of patients with HCC.
Methods
We measured telomere length in tumor and adjacent non-tumor tissues from 126 persons with HCC in the United States (U.S.) who were followed for mortality outcomes. Relative telomere length (RTL) was measured by a monochrome multiplex quantitative polymerase chain reaction assay. Multivariable Cox proportional hazards modeling was used to calculate hazard ratios (HRs) and 95% CIs for the association between telomere length and allcause mortality. We also examined associations between telomere length and patient characteristics using multiple linear regression.
Results
During a mean follow-up of 6.0 years, 79 deaths occurred among 114 individuals for whom survival data were available. The ratio of RTL in tumor relative to non-tumor tissue was greater for individuals with regional or distant stage tumors (0.97) than localized stage tumors (0.77), and for individuals with grade III or IV tumors (0.95) than grade II (0.88) or grade I (0.67) tumors. An RTL ratio >= 1 was not associated with survival (HR 0.92, 95% CI 0.55, 1.55) compared to a ratio <1, after adjusting for age at diagnosis, sex, tumor stage and tumor size. Similarly, RTL in the tumor and non-tumor tissue, respectively, were not associated with survival.
Conclusions
This U.S. based study found that telomeres may be longer in more aggressive HCCs. There was no evidence, however, that telomere length was associated with survival of patients with HCC. Future investigations are warranted to clarify the role of telomere length in HCC prognosis.
C1 [Yang, Baiyu; Dagnall, Casey L.; Hicks, Belynda D.; McGlynn, Katherine A.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Shebl, Fatma M.] Yale Univ, Sch Publ Hlth, New Haven, CT 06520 USA.
[Sternberg, Lawrence R.; Warner, Andrew C.] Frederick Natl Lab Canc Res, Pathol Histotechnol Lab, Frederick, MD 21701 USA.
[Kleiner, David E.; Edelman, Daniel C.; Gomez, Allison; Meltzer, Paul S.] NCI, Ctr Canc Res, Bethesda, MD 20892 USA.
[Dagnall, Casey L.; Hicks, Belynda D.] Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Canc Genom Res Lab, Frederick, MD 20892 USA.
[Altekruse, Sean F.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Hernandez, Brenda Y.] Univ Hawaii, Ctr Canc, Honolulu, HI 96813 USA.
[Lynch, Charles F.] Univ Iowa, Coll Publ Hlth, Iowa City, IA 52242 USA.
RP Yang, BY (reprint author), NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
EM baiyu.yang@nih.gov
OI Dagnall, Casey/0000-0001-7334-4718
FU Intramural Research Program of the National Institutes of Health,
National Cancer Institute
FX This research was supported by the Intramural Research Program of the
National Institutes of Health, National Cancer Institute.
NR 38
TC 0
Z9 0
U1 2
U2 2
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD NOV 23
PY 2016
VL 11
IS 11
AR e0166828
DI 10.1371/journal.pone.0166828
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA ED5KB
UT WOS:000388889500036
PM 27880792
ER
PT J
AU Collins, FS
Riley, WT
AF Collins, Francis S.
Riley, William T.
TI NIH's transformative opportunities for the behavioral and social
sciences
SO Science Translational Medicine
LA English
DT Editorial Material
C1 [Collins, Francis S.] US Natl Inst Hlth NIH, Bethesda, MD USA.
[Riley, William T.] US NIH, Off Behav & Social Sci Res, Bethesda, MD 20191 USA.
RP Riley, WT (reprint author), US NIH, Off Behav & Social Sci Res, Bethesda, MD 20191 USA.
EM wiriley@mail.nih.gov
NR 6
TC 1
Z9 1
U1 0
U2 0
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 1946-6234
EI 1946-6242
J9 SCI TRANSL MED
JI Sci. Transl. Med.
PD NOV 23
PY 2016
VL 8
IS 366
AR 366ed14
DI 10.1126/scitranslmed.aai9374
PG 2
WC Cell Biology; Medicine, Research & Experimental
SC Cell Biology; Research & Experimental Medicine
GA EE2XQ
UT WOS:000389449400001
PM 27881821
ER
PT J
AU Dey, D
Bagarova, J
Hatsell, SJ
Armstrong, KA
Huang, L
Ermann, J
Vonner, AJ
Shen, Y
Mohedas, AH
Lee, A
Eekhoff, EMW
van Schie, A
Demay, MB
Keller, C
Wagers, AJ
Economides, AN
Yu, PB
AF Dey, Devaveena
Bagarova, Jana
Hatsell, Sarah J.
Armstrong, Kelli A.
Huang, Lily
Ermann, Joerg
Vonner, Ashley J.
Shen, Yue
Mohedas, Agustin H.
Lee, Arthur
Eekhoff, Elisabeth M. W.
van Schie, Annelies
Demay, Marie B.
Keller, Charles
Wagers, Amy J.
Economides, Aris N.
Yu, Paul B.
TI Two tissue-resident progenitor lineages drive distinct phenotypes of
heterotopic ossification
SO Science Translational Medicine
LA English
DT Article
ID SMOOTH-MUSCLE-CELLS; SKELETAL-MUSCLE; I RECEPTOR; NATURAL-HISTORY;
TRANSGENIC MICE; BONE-FORMATION; PROGRESSIVA; MOUSE; ALK2; CONTRIBUTE
AB Fibrodysplasia ossificans progressiva (FOP), a congenital heterotopic ossification (HO) syndrome caused by gain-of-function mutations of bone morphogenetic protein (BMP) type I receptor ACVR1, manifests with progressive ossification of skeletal muscles, tendons, ligaments, and joints. In this disease, HO can occur in discrete flares, often triggered by injury or inflammation, or may progress incrementally without identified triggers. Mice harboring an Acvr1(R206H) knock-in allele recapitulate the phenotypic spectrum of FOP, including injury-responsive intramuscular HO and spontaneous articular, tendon, and ligament ossification. The cells that drive HO in these diverse tissues can be compartmentalized into two lineages: an Scx(+) tendon-derived progenitor that mediates endochondral HO of ligaments and joints without exogenous injury, and a muscle-resident interstitial Mx1(+) population that mediates intramuscular, injury-dependent endochondral HO. Expression of Acvr1(R206H) in either lineage confers aberrant gain of BMP signaling and chondrogenic differentiation in response to activin A and gives rise to mutation-expressing hypertrophic chondrocytes in HO lesions. Compared to Acvr1(R206H), expression of the man-made, ligand-independent ACVR1(Q207D) mutation accelerates and increases the penetrance of all observed phenotypes, but does not abrogate the need for antecedent injury in muscle HO, demonstrating the need for an injury factor in addition to enhanced BMP signaling. Both injury-dependent intramuscular and spontaneous ligament HO in Acvr(1R206H) knock-in mice were effectively controlled by the selective ACVR1 inhibitor LDN-212854. Thus, diverse phenotypes of HO found in FOP are rooted in cell-autonomous effects of dysregulated ACVR1 signaling in nonoverlapping tissue-resident progenitor pools that may be addressed by systemic therapy or by modulating injury-mediated factors involved in their local recruitment.
C1 [Dey, Devaveena; Bagarova, Jana; Armstrong, Kelli A.; Vonner, Ashley J.; Shen, Yue; Mohedas, Agustin H.; Yu, Paul B.] Harvard Med Sch, Brigham & Womens Hosp, Div Cardiovasc Med, Dept Med, 75 Francis St, Boston, MA 02115 USA.
[Hatsell, Sarah J.; Huang, Lily; Economides, Aris N.] Regeneron Pharmaceut Inc, 777 Old Saw Mill River Rd, Tarrytown, NY 10591 USA.
[Ermann, Joerg] Harvard Med Sch, Brigham & Womens Hosp, Div Rheumatol Immunol & Allergy, Dept Med, Boston, MA 02115 USA.
[Lee, Arthur] NIH, Natl Ctr Adv Translat Sci, Rockville, MD 20850 USA.
[Eekhoff, Elisabeth M. W.; van Schie, Annelies] Vrije Univ Amsterdam, Med Ctr, Dept Internal Med, Endocrine Sect, POB 7057, NL-1007 MB Amsterdam, Netherlands.
[Eekhoff, Elisabeth M. W.; van Schie, Annelies] Vrije Univ Amsterdam, Med Ctr, Dept Epidemiol & Biostat, POB 7057, NL-1007 MB Amsterdam, Netherlands.
[Demay, Marie B.] Harvard Med Sch, Massachusetts Gen Hosp, Endocrine Unit, 55 Fruit St, Boston, MA 02114 USA.
[Keller, Charles] Childrens Canc Therapy Dev Inst, 12655 SW Beaverdam Road West, Beaverton, OR 97005 USA.
[Wagers, Amy J.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA.
[Wagers, Amy J.] Harvard Stem Cell Inst, Cambridge, MA 02138 USA.
[Wagers, Amy J.] Beth Israel Deaconess Med Ctr, Joslin Diabet Ctr, Boston, MA 02215 USA.
[Economides, Aris N.] Regeneron Genet Ctr, Tarrytown, NY 10591 USA.
RP Yu, PB (reprint author), Harvard Med Sch, Brigham & Womens Hosp, Div Cardiovasc Med, Dept Med, 75 Francis St, Boston, MA 02115 USA.
EM pbyu@partners.org
OI Economides, Aris/0000-0002-6508-8942
FU US NIH [HL079943, AR057374, DK036836, HL100402]; Brigham and Women's
Hospital Cardiovascular Division T32 [HL007604]; National Institute of
Arthritis and Musculoskeletal and Skin Diseases P30 Center for Skeletal
Research Core [AR066261]; Department of Defense [MR140072]; Harvard Stem
Cell Institute Seed Award; International FOP Association Competitive
Grant Award; Harvard Stem Cell Institute; Pulmonary Hypertension
Association Clinician Scientist Career Development Award; Leducq
Foundation Transatlantic Network of Excellence Award; Howard Hughes
Medical Institute Early Career Physician-Scientist Award; Massachusetts
Technology Transfer Award
FX This work was supported by the US NIH [HL079943 (to P.B.Y.), AR057374
(to P.B.Y.), DK036836 (to A.J.W.), and HL100402 (to A.J.W.)], Brigham
and Women's Hospital Cardiovascular Division T32 [HL007604 (to D.D.)],
National Institute of Arthritis and Musculoskeletal and Skin Diseases
P30 Center for Skeletal Research Core (AR066261), Department of Defense
[MR140072 (to P.B.Y.)], Harvard Stem Cell Institute Seed Award (to
P.B.Y.), International FOP Association Competitive Grant Award (to
P.B.Y. and Y.S.), Harvard Stem Cell Institute funding for the Joslin
Diabetes Center Flow Core Facility, Pulmonary Hypertension Association
Clinician Scientist Career Development Award (to P.B.Y.), Leducq
Foundation Transatlantic Network of Excellence Award (to P.B.Y.), Howard
Hughes Medical Institute Early Career Physician-Scientist Award (to
P.B.Y.), and Massachusetts Technology Transfer Award (to P.B.Y.).
NR 60
TC 2
Z9 2
U1 5
U2 5
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 1946-6234
EI 1946-6242
J9 SCI TRANSL MED
JI Sci. Transl. Med.
PD NOV 23
PY 2016
VL 8
IS 366
AR 366ra163
DI 10.1126/scitranslmed.aaf1090
PG 13
WC Cell Biology; Medicine, Research & Experimental
SC Cell Biology; Research & Experimental Medicine
GA EE2XQ
UT WOS:000389449400004
PM 27881824
ER
PT J
AU Iwanami, N
Sikora, K
Richter, AS
Monnich, M
Guerri, L
Soza-Ried, C
Lawir, DF
Mateos, F
Hess, I
O'Meara, CP
Schorpp, M
Boehm, T
AF Iwanami, Norimasa
Sikora, Katarzyna
Richter, Andreas S.
Moennich, Maren
Guerri, Lucia
Soza-Ried, Cristian
Lawir, Divine-Fondzenyuy
Mateos, Fernando
Hess, Isabell
O'Meara, Connor P.
Schorpp, Michael
Boehm, Thomas
TI Forward Genetic Screens in Zebrafish Identify Pre-mRNA-Processing
Pathways Regulating Early T Cell Development
SO CELL REPORTS
LA English
DT Article
ID SPINAL MUSCULAR-ATROPHY; DESIGN PRINCIPLES; RECYCLING FACTOR; NUCLEAR
IMPORT; B-CELLS; EXPRESSION; PROTEIN; MODEL; HEMATOPOIESIS; COMPONENTS
AB Lymphocytes represent basic components of vertebrate adaptive immune systems, suggesting the utility of non-mammalian models to define the molecular basis of their development and differentiation. Our forward genetic screens in zebrafish for recessive mutations affecting early T cell development revealed several major genetic pathways. The identification of lineage-specific transcription factors and specific components of cytokine signaling and DNA replication and/or repair pathways known from studies of immunocompromisedmammals provided an evolutionary cross-validation of the screen design. Unexpectedly, however, genes encoding proteins required for pre-mRNA processing were enriched in the collection of mutants identified here. In both zebrafish and mice, deficiency of the splice regulator TNPO3 impairs intrathymic T cell differentiation, illustrating the evolutionarily conserved and cell-type-specific functions of certain pre-mRNA-processing factors for T cell development.
C1 [Iwanami, Norimasa; Sikora, Katarzyna; Moennich, Maren; Guerri, Lucia; Soza-Ried, Cristian; Lawir, Divine-Fondzenyuy; Mateos, Fernando; Hess, Isabell; O'Meara, Connor P.; Schorpp, Michael; Boehm, Thomas] Max Planck Inst Immunbiol & Epigenet, Dept Dev Immunol, Stubeweg 51, D-79108 Freiburg, Germany.
[Sikora, Katarzyna; Richter, Andreas S.] Max Planck Inst Immunbiol & Epigenet, Bioinformat Unit, Stubeweg 51, D-79108 Freiburg, Germany.
[Richter, Andreas S.] Genedata AG, CH-4053 Basel, Switzerland.
[Moennich, Maren] Univ Copenhagen, Wilhelm Johannsen Ctr Funct Genome Res, Dept Cellular & Mol Med, Blegdamsvej 3, DK-2200 Copenhagen, Denmark.
[Guerri, Lucia] NIAAA, Neurogenet Lab, NIH, 5625 Fishers Lane, Rockville, MD 20852 USA.
[Soza-Ried, Cristian] Fdn Oncoloop, Antonio Varas 710, Santiago, Chile.
[Soza-Ried, Cristian] Univ Andres Bellos, Fac Med, Republ 330, Santiago, Chile.
RP Boehm, T (reprint author), Max Planck Inst Immunbiol & Epigenet, Dept Dev Immunol, Stubeweg 51, D-79108 Freiburg, Germany.
EM boehm@immunbio.mpg.de
OI Richter, Andreas S./0000-0002-4166-0991
FU Max Planck Society; European Research Council under the European Union's
Seventh Framework Programme (FP7) ERC Grant [323126]
FX This project has received funding from the Max Planck Society and the
European Research Council under the European Union's Seventh Framework
Programme (FP7/2007-2013) ERC Grant Agreement 323126. The mutant screen
was conducted in collaboration with the Tubingen 2000 Screen Consortium
and the Freiburg Screening Group; their members are listed in
Supplemental Experimental Procedures. We thank W. Wiest for initial
identification of the WW18/10 mutant, B. Kanzler for help in the
establishment of the mouse Tnpo3 mutant, D. Bonsch for excellent animal
care, and U. Bonisch, E. Betancourt, and S. Diehl for help with
next-generation sequencing.
NR 41
TC 0
Z9 0
U1 2
U2 2
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 2211-1247
J9 CELL REP
JI Cell Reports
PD NOV 22
PY 2016
VL 17
IS 9
BP 2259
EP 2270
DI 10.1016/j.celrep.2016.11.003
PG 12
WC Cell Biology
SC Cell Biology
GA EG2SE
UT WOS:000390893600009
PM 27880902
ER
PT J
AU Kim, JW
Yang, HJ
Brooks, MJ
Zelinger, L
Karakulah, G
Gotoh, N
Boleda, A
Gieser, L
Giuste, F
Whitaker, DT
Walton, A
Villasmil, R
Barb, JJ
Munson, PJ
Kaya, KD
Chaitankar, V
Cogliati, T
Swaroop, A
AF Kim, Jung-Woong
Yang, Hyun-Jin
Brooks, Matthew John
Zelinger, Lina
Karakulah, Gokhan
Gotoh, Norimoto
Boleda, Alexis
Gieser, Linn
Giuste, Felipe
Whitaker, Dustin Thad
Walton, Ashley
Villasmil, Rafael
Barb, Jennifer Joanna
Munson, Peter Jonathan
Kaya, Koray Dogan
Chaitankar, Vijender
Cogliati, Tiziana
Swaroop, Anand
TI NRL-Regulated Transcriptome Dynamics of Developing Rod Photoreceptors
SO CELL REPORTS
LA English
DT Article
ID NUCLEAR RECEPTOR NR2E3; MOUSE RETINA; MAMMALIAN RETINA; INTRON
RETENTION; CEREBRAL-CORTEX; LEUCINE-ZIPPER; BIPOLAR CELLS; IN-VITRO;
EXPRESSION; DIFFERENTIATION
AB Gene regulatory networks (GRNs) guiding differentiation of cell types and cell assemblies in the nervous system are poorly understood because of inherent complexities and interdependence of signaling pathways. Here, we report transcriptome dynamics of differentiating rod photoreceptors in the mammalian retina. Given that the transcription factor NRL determines rod cell fate, we performed expression profiling of developing NRL-positive (rods) and NRL-negative (S-cone-like) mouse photoreceptors. We identified a large-scale, sharp transition in the transcriptome landscape between postnatal days 6 and 10 concordant with rod morphogenesis. Rod-specific temporal DNA methylation corroborated gene expression patterns. De novo assembly and alternative splicing analyses revealed previously unannotated rod-enriched transcripts and the role of NRL in transcript maturation. Furthermore, we defined the relationship of NRL with other transcriptional regulators and downstream cognate effectors. Our studies provide the framework for comprehensive system-level analysis of the GRN underlying the development of a single sensory neuron, the rod photoreceptor.
C1 [Kim, Jung-Woong; Yang, Hyun-Jin; Brooks, Matthew John; Zelinger, Lina; Karakulah, Gokhan; Gotoh, Norimoto; Boleda, Alexis; Gieser, Linn; Giuste, Felipe; Whitaker, Dustin Thad; Walton, Ashley; Kaya, Koray Dogan; Chaitankar, Vijender; Cogliati, Tiziana; Swaroop, Anand] NEI, Neurobiol Neurodegenerat & Repair Lab, NIH, Bethesda, MD 20892 USA.
[Kim, Jung-Woong] Chung Ang Univ, Dept Life Sci, Seoul 06974, South Korea.
[Gotoh, Norimoto] Kyoto Univ, Grad Sch Med, Ctr Genom Med, Kyoto 6068501, Japan.
[Whitaker, Dustin Thad] Texas A&M Univ, Texas A&M Inst Neurosci, College Stn, TX 77843 USA.
[Villasmil, Rafael] NEI, Flow Cytometry Core, NIH, Bethesda, MD 20892 USA.
[Barb, Jennifer Joanna; Munson, Peter Jonathan] NIH, Math & Stat Comp Lab, Ctr Informat Technol, Bldg 10, Bethesda, MD 20892 USA.
[Karakulah, Gokhan] Dokuz Eylul Univ, Izmir Int Biomed & Genome Inst, TR-35340 Inciralti, Turkey.
RP Swaroop, A (reprint author), NEI, Neurobiol Neurodegenerat & Repair Lab, NIH, Bethesda, MD 20892 USA.
EM swaroopa@nei.nih.gov
OI Karakulah, Gokhan/0000-0001-6706-1375
FU Intramural Research Program of the NEI [EY000450, EY000546]; National
Research Foundation of Korea [2015R1C1A1A01055466, 2016R1A4A1008035]
FX We thank Julie Laux of the NEI flow cytometry core for assistance. This
research was supported by Intramural Research Program of the NEI (grants
EY000450 and EY000546) and the National Research Foundation of Korea
(grants 2015R1C1A1A01055466 and 2016R1A4A1008035) and utilized the
high-performance computational capabilities of the Biowulf Linux cluster
at the NIH (https://hpc.nih.gov).
NR 72
TC 0
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U1 3
U2 3
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 2211-1247
J9 CELL REP
JI Cell Reports
PD NOV 22
PY 2016
VL 17
IS 9
BP 2460
EP 2473
DI 10.1016/j.celrep.2016.10.074
PG 14
WC Cell Biology
SC Cell Biology
GA EG2SE
UT WOS:000390893600024
PM 27880916
ER
PT J
AU Imashimizu, M
Afek, A
Takahashi, H
Lubkowska, L
Lukatsky, DB
AF Imashimizu, Masahiko
Afek, Ariel
Takahashi, Hiroki
Lubkowska, Lucyna
Lukatsky, David B.
TI Control of transcriptional pausing by biased thermal fluctuations on
repetitive genomic sequences
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE repetitive DNA sequence elements; nonconsensus protein-DNA binding; RNA
polymerase; backtracking; thermal fluctuations
ID RNA-POLYMERASE-II; PROTEIN-DNA BINDING; ESCHERICHIA-COLI; IN-VIVO;
ANGSTROM RESOLUTION; STRUCTURAL BASIS; ELONGATION; BACKTRACKING;
MECHANISM; TRANSLOCATION
AB In the process of transcription elongation, RNA polymerase (RNAP) pauses at highly nonrandom positions across genomic DNA, broadly regulating transcription; however, molecular mechanisms responsible for the recognition of such pausing positions remain poorly understood. Here, using a combination of statistical mechanical modeling and high-throughput sequencing and biochemical data, we evaluate the effect of thermal fluctuations on the regulation of RNAP pausing. We demonstrate that diffusive backtracking of RNAP, which is biased by repetitive DNA sequence elements, causes transcriptional pausing. This effect stems from the increased microscopic heterogeneity of an elongation complex, and thus is entropydominated. This report shows a linkage between repetitive sequence elements encoded in the genome and regulation of RNAP pausing driven by thermal fluctuations.
C1 [Imashimizu, Masahiko; Lubkowska, Lucyna] NCI, Ctr Canc Res, Frederick, MD 21702 USA.
[Imashimizu, Masahiko; Takahashi, Hiroki] Chiba Univ, Med Mycol Res Ctr, Chuo Ku, 1-8-1 Inohana, Chiba 2608673, Japan.
[Imashimizu, Masahiko] Univ Tokyo, Inst Med Sci, Minato Ku, Tokyo 1088639, Japan.
[Afek, Ariel; Lukatsky, David B.] Ben Gurion Univ Negev, Dept Chem, IL-8410501 Beer Sheva, Israel.
[Afek, Ariel] Duke Univ, Med Ctr, Dept Biostat & Bioinformat, Durham, NC 27710 USA.
[Takahashi, Hiroki] Chiba Univ, Mol Chiral Res Ctr, Inage Ku, 1-33 Yayoi Cho, Chiba 2638522, Japan.
RP Imashimizu, M (reprint author), NCI, Ctr Canc Res, Frederick, MD 21702 USA.; Imashimizu, M (reprint author), Chiba Univ, Med Mycol Res Ctr, Chuo Ku, 1-8-1 Inohana, Chiba 2608673, Japan.; Imashimizu, M (reprint author), Univ Tokyo, Inst Med Sci, Minato Ku, Tokyo 1088639, Japan.; Lukatsky, DB (reprint author), Ben Gurion Univ Negev, Dept Chem, IL-8410501 Beer Sheva, Israel.
EM imashi@ims.u-tokyo.ac.jp; lukatsky@bgu.ac.il
FU Intramural Research Program of the NIH/National Cancer Institute; MEXT
KAKENHI [16K18671, 16H06279]; Japan Society for the Promotion of Science
KAKENHI [16H06692]; Integrated DNA Technologies postdoctoral fellowship
FX We thank Mikhail Kashlev and Yoshikazu Nakamura for supporting our
research and for helpful discussions, Nobuo Shimamoto and Donald L.
Court for critical reading of the manuscript and for insightful
comments, and Taku Oshima for helpful discussions regarding the PWM
analysis. M.I. is also grateful to Nobuo Shimamoto for discussions
regarding chemical kinetics. This work was supported by the Intramural
Research Program of the NIH/National Cancer Institute (to Mikhail
Kashlev), by MEXT KAKENHI Grants 16K18671 and 16H06279 (to H.T.), and by
Japan Society for the Promotion of Science KAKENHI Grant 16H06692 (to
M.I.). A. A. is supported by an Integrated DNA Technologies postdoctoral
fellowship.
NR 52
TC 0
Z9 0
U1 0
U2 0
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD NOV 22
PY 2016
VL 113
IS 47
BP E7409
EP E7417
DI 10.1073/pnas.1607760113
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA ED4OY
UT WOS:000388830700010
PM 27830653
ER
PT J
AU Yaffe, D
Vergara-Jaque, A
Forrest, LR
Schuldiner, S
AF Yaffe, Dana
Vergara-Jaque, Ariela
Forrest, Lucy R.
Schuldiner, Shimon
TI Emulating proton-induced conformational changes in the vesicular
monoamine transporter VMAT2 by mutagenesis
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE neurotransmitter transporter; ion coupling; reserpine; tetrabenazine
ID BOVINE CHROMAFFIN GRANULES; PROTEIN SECONDARY STRUCTURE; AMINE
TRANSPORTER; NEUROTRANSMITTER TRANSPORTERS; RESERPINE BINDING;
MEMBRANE-PROTEINS; CATECHOLAMINE TRANSPORTER; NONCOMPETITIVE INHIBITOR;
SUBSTRATE RECOGNITION; FUCOSE TRANSPORTER
AB Neurotransporters located in synaptic vesicles are essential for communication between nerve cells in a process mediated by neurotransmitters. Vesicular monoamine transporter (VMAT), a member of the largest superfamily of transporters, mediates transport of monoamines to synaptic vesicles and storage organelles in a process that involves exchange of two H+ per substrate. VMAT transport is inhibited by the competitive inhibitor reserpine, a second-line agent to treat hypertension, and by the noncompetitive inhibitor tetrabenazine, presently in use for symptomatic treatment of hyperkinetic disorders. During the transport cycle, VMAT is expected to occupy at least three different conformations: cytoplasm-facing, occluded, and lumen-facing. The lumen-to cytoplasm-facing transition, facilitated by protonation of at least one of the essential membrane-embedded carboxyls, generates a binding site for reserpine. Here we have identified residues in the cytoplasmic gate and show that mutations that disrupt the interactions in this gate also shift the equilibrium toward the cytoplasm-facing conformation, emulating the effect of protonation. These experiments provide significant insight into the role of proton translocation in the conformational dynamics of a mammalian H+-coupled antiporter, and also identify key aspects of the mode of action and binding of two potent inhibitors of VMAT2: reserpine binds the cytoplasm-facing conformation, and tetrabenazine binds the lumen-facing conformation.
C1 [Yaffe, Dana; Schuldiner, Shimon] Hebrew Univ Jerusalem, Alexander Silberman Inst Life Sci, Dept Biol Chem, IL-91904 Jerusalem, Israel.
[Vergara-Jaque, Ariela; Forrest, Lucy R.] NINDS, Computat Struct Biol Sect, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
RP Schuldiner, S (reprint author), Hebrew Univ Jerusalem, Alexander Silberman Inst Life Sci, Dept Biol Chem, IL-91904 Jerusalem, Israel.
EM shimon.schuldiner@huji.ac.il
OI Schuldiner, Shimon/0000-0002-4874-6237
FU National Institutes of Health Grant [NS16708]; Israel-USA Binational
Science Foundation Grant [2013198]; Division of Intramural Research of
the National Institute of Neurological Disorders and Stroke, NIH;
L'Oreal Chile-UNESCO Women in Science Fellowship; L'Oreal-UNESCO Rising
Talent Award
FX We thank Dina Listov, Yifat Levine, and Shai Fainsod for help during the
course of this work. S.S. is Mathilda Marks-Kennedy Professor of
Biochemistry at the Hebrew University of Jerusalem. This research was
supported by National Institutes of Health Grant NS16708 (to S.S.);
Israel-USA Binational Science Foundation Grant 2013198 (to S.S.); and
the Division of Intramural Research of the National Institute of
Neurological Disorders and Stroke, NIH (L.R.F. and A.V.-J.). A.V.-J. is
a recipient of the L'Oreal Chile-UNESCO Women in Science Fellowship and
the L'Oreal-UNESCO Rising Talent Award.
NR 63
TC 0
Z9 0
U1 1
U2 1
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 NOV 22
PY 2016
VL 113
IS 47
BP E7390
EP E7398
DI 10.1073/pnas.1605162113
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA ED4OY
UT WOS:000388830700008
PM 27821772
ER
PT J
AU Murai, J
Feng, Y
Yu, GYK
Ru, YB
Tang, SW
Shen, YQ
Pommier, Y
AF Murai, Junko
Feng, Ying
Yu, Guoying K.
Ru, Yuanbin
Tang, Sai-Wen
Shen, Yuqiao
Pommier, Yves
TI Resistance to PARP inhibitors by SLFN11 inactivation can be overcome by
ATR inhibition
SO Oncotarget
LA English
DT Article
DE PARP-trapping; ATR; PARP inhibitor; BRCA; homologous recombination
ID DNA-REPLICATION INITIATION; CELL LUNG-CANCER; BMN 673; POLY(ADP-RIBOSE)
POLYMERASE; HOMOLOGOUS RECOMBINATION; MOLECULAR PATHWAYS;
DRUG-SENSITIVITY; DAMAGING AGENTS; REPAIR; COMBINATION
AB Poly(ADP-ribose) polymerase inhibitors (PARPIs) kill cancer cells by trapping PARP1 and PARP2. Talazoparib, the most potent PARPI inhibitor (PARPI), exhibits remarkable selectivity among the NCI-60 cancer cell lines beyond BRCA inactivation. Our genomic analyses reveal high correlation between response to talazoparib and Schlafen 11 (SLFN11) expression. Causality was established in four isogenic SLFN11-positive and -negative cell lines and extended to olaparib. Response to the talazoparib-temozolomide combination was also driven by SLFN11 and validated in 36 small cell lung cancer cell lines, and in xenograft models. Resistance in SLFN11-deficient cells was caused neither by impaired drug penetration nor by activation of homologous recombination. Rather, SLFN11 induced irreversible and lethal replication inhibition, which was independent of ATR-mediated S-phase checkpoint. The resistance to PARPIs by SLFN11 inactivation was overcome by ATR inhibition, mechanistically because SLFN11-deficient cells solely rely on ATR activation for their survival under PARPI treatment. Our study reveals that SLFN11 inactivation, which is common (similar to 45%) in cancer cells, is a novel and dominant resistance determinant to PARPIs.
C1 [Murai, Junko; Tang, Sai-Wen; Pommier, Yves] NCI, Dev Therapeut Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Murai, Junko; Tang, Sai-Wen; Pommier, Yves] NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Feng, Ying; Yu, Guoying K.; Ru, Yuanbin; Shen, Yuqiao] BioMarin Pharmaceut Inc, Novato, CA USA.
[Tang, Sai-Wen] Stanford Univ, Dept Med, Sch Med, Div Blood & Marrow Transplantat, Stanford, CA 94305 USA.
RP Pommier, Y (reprint author), NCI, Dev Therapeut Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.; Pommier, Y (reprint author), NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM pommier@nih.gov
FU Intramural Program, Center for Cancer Research, of the National Cancer
Institute, NIH [BC006150]
FX Our studies are supported by the Intramural Program, Center for Cancer
Research, of the National Cancer Institute, NIH (BC006150).
NR 57
TC 2
Z9 2
U1 4
U2 4
PU IMPACT JOURNALS LLC
PI ALBANY
PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA
SN 1949-2553
J9 ONCOTARGET
JI Oncotarget
PD NOV 22
PY 2016
VL 7
IS 47
BP 76534
EP 76550
DI 10.18632/oncotarget.12266
PG 17
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA EE5GK
UT WOS:000389633400016
PM 27708213
ER
PT J
AU Kwon, M
Kim, JH
Rybak, Y
Luna, A
Choi, CH
Chung, JY
Hewitt, SM
Adem, A
Tubridy, E
Lin, J
Libutti, SK
AF Kwon, Mijung
Kim, Jae-Hoon
Rybak, Yevangelina
Luna, Alex
Choi, Chel Hun
Chung, Joon-Yong
Hewitt, Stephen M.
Adem, Asha
Tubridy, Elizabeth
Lin, Juan
Libutti, Steven K.
TI Reduced expression of FILIP1L, a novel WNT pathway inhibitor, is
associated with poor survival, progression and chemoresistance in
ovarian cancer
SO Oncotarget
LA English
DT Article
DE ovarian cancer; prognosis; metastasis; chemoresistance; WNT
ID EPITHELIAL-MESENCHYMAL TRANSITION; INTERACTING PROTEIN 1-LIKE;
BETA-CATENIN; CERVICAL-CANCER; PROGNOSTIC-SIGNIFICANCE; PHENOTYPIC
PLASTICITY; COLORECTAL-CANCER; ENDOTHELIAL-CELLS; SIGNALING PATHWAY;
DOWN-REGULATION
AB Filamin A interacting protein 1-like (FILIP1L) is an inhibitor of the canonical WNT pathway. WNT/beta-catenin signaling and its downstream pathway, epithelial-to- mesenchymal transition (EMT), play a key role in ovarian cancer metastasis and chemoresistance. To study the clinical implications of FILIP1L in regulating the WNT/beta-catenin pathway, the expression of FILIP1L, beta-catenin, SNAIL and SLUG was analyzed by immunohistochemistry on tissue microarrays of 369 ovarian samples ranging from normal to metastatic. In addition, the results were validated in mouse model and in vitro cell culture. In the present study, we demonstrated that FILIP1L expression was inversely correlated with poor prognosis, stage and chemoresistance in ovarian cancer. Notably, low FILIP1L expression was independent negative prognostic factor with respect to overall and disease-free survival. FILIP1L inhibited peritoneal metastases in orthotopic mouse model. FILIP1L knockdown induced chemoresistance in ovarian cancer cells and this phenotype was rescued by simultaneous knockdown of FILIP1L and SLUG, an EMT activator. We also demonstrated that FILIP1L regulates beta-catenin degradation. FILIP1L co-localizes with phospho-beta-catenin and increases phospho-beta-catenin at the centrosomes, destined for proteosomal degradation. Finally, we showed that FILIP1L regulates EMT. Overall, these findings suggest that FILIP1L promotes beta-catenin degradation and suppresses EMT, thereby inhibiting metastases and chemoresistance. Our study provides the first clinical relevance of FILIP1L in human cancer, and suggests that FILIP1L may be a novel prognostic marker for chemotherapy in ovarian cancer patients. Further, the modulation of FILIP1L expression may have the potential to be a target for cancer therapy.
C1 [Kwon, Mijung; Rybak, Yevangelina; Luna, Alex; Adem, Asha; Tubridy, Elizabeth; Libutti, Steven K.] Albert Einstein Coll Med, Dept Surg, Bronx, NY 10461 USA.
[Lin, Juan] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Div Biostat, Bronx, NY 10461 USA.
[Kim, Jae-Hoon] Yonsei Univ, Coll Med, Gangnam Severance Hosp, Dept Obstet & Gynecol, Seoul 135720, South Korea.
[Kim, Jae-Hoon] Yonsei Univ, Coll Med, Inst Womens Life Med Sci, Seoul 135720, South Korea.
[Choi, Chel Hun] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Obstet & Gynecol, Seoul 135710, South Korea.
[Choi, Chel Hun; Chung, Joon-Yong; Hewitt, Stephen M.] NCI, Expt Pathol Lab, Pathol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA.
RP Kwon, M; Libutti, SK (reprint author), Albert Einstein Coll Med, Dept Surg, Bronx, NY 10461 USA.
EM mijung.kwon@einstein.yu.edu; slibutti@montefiore.org
OI Chung, Joon-Yong/0000-0001-5041-5982
FU Office of the Assistant Secretary of Defense for Health Affairs through
the Ovarian Cancer Research Program [W81XWH-15-1-0369]; Intramural
Research Program of the National Institutes of Health, National Cancer
Institute, Center for Cancer Research
FX This work was supported in part by the Office of the Assistant Secretary
of Defense for Health Affairs through the Ovarian Cancer Research
Program under Award No. W81XWH-15-1-0369. Opinions, interpretations,
conclusions and recommendations are those of the author and are not
necessarily endorsed by the Department of Defense. This work was also
supported in part by the Intramural Research Program of the National
Institutes of Health, National Cancer Institute, Center for Cancer
Research.
NR 82
TC 0
Z9 0
U1 1
U2 1
PU IMPACT JOURNALS LLC
PI ALBANY
PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA
SN 1949-2553
J9 ONCOTARGET
JI Oncotarget
PD NOV 22
PY 2016
VL 7
IS 47
BP 77052
EP 77070
DI 10.18632/oncotarget.12784
PG 19
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA EE5GK
UT WOS:000389633400058
PM 27776341
ER
PT J
AU Maachani, UB
Shankavaram, U
Kramp, T
Tofilon, PJ
Camphausen, K
Tandle, AT
AF Maachani, Uday B.
Shankavaram, Uma
Kramp, Tamalee
Tofilon, Philip J.
Camphausen, Kevin
Tandle, Anita T.
TI FOXM1 and STAT3 interaction confers radioresistance in glioblastoma
cells
SO Oncotarget
LA English
DT Article
DE glioblastoma multiforme; FOXM1; STAT3; glioma stem cells; radio
resistance
ID FORKHEAD BOX M1; TUMOR STEM-CELLS; DNA-DAMAGE; TRANSCRIPTION FACTOR;
ANTICANCER THERAPY; GLIOMA-CELLS; CANCER; REPAIR; EXPRESSION; SURVIVAL
AB Glioblastoma multiforme (GBM) continues to be the most frequently diagnosed and lethal primary brain tumor. Adjuvant chemo-radiotherapy remains the standard of care following surgical resection. In this study, using reverse phase protein arrays (RPPAs), we assessed the biological effects of radiation on signaling pathways to identify potential radiosensitizing molecular targets. We identified subsets of proteins with clearly concordant/discordant behavior between irradiated and non-irradiated GBM cells in vitro and in vivo. Moreover, we observed high expression of Forkhead box protein M1 (FOXM1) in irradiated GBM cells both in vitro and in vivo. Recent evidence of FOXM1 as a master regulator of metastasis and its important role in maintaining neural, progenitor, and GBM stem cells, intrigued us to validate it as a radiosensitizing target. Here we show that FOXM1 inhibition radiosensitizes GBM cells by abrogating genes associated with cell cycle progression and DNA repair, suggesting its role in cellular response to radiation. Further, we demonstrate that radiation induced stimulation of FOXM1 expression is dependent on STAT3 activation. Co-immunoprecipitation and co-localization assays revealed physical interaction of FOXM1 with phosphorylated STAT3 under radiation treatment. In conclusion, we hypothesize that FOXM1 regulates radioresistance via STAT3 in GBM cells. We also, show GBM patients with high FOXM1 expression have poor prognosis. Collectively our observations might open novel opportunities for targeting FOXM1 for effective GBM therapy.
C1 [Maachani, Uday B.; Shankavaram, Uma; Kramp, Tamalee; Tofilon, Philip J.; Camphausen, Kevin; Tandle, Anita T.] NCI, Radiat Oncol Branch, NIH, Bldg 10, Bethesda, MD 20892 USA.
RP Tandle, AT (reprint author), NCI, Radiat Oncol Branch, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM tandlea@mail.nih.gov
FU Intramural Research Program of the National Institutes of Health,
National Cancer Institute
FX This research was supported by the Intramural Research Program of the
National Institutes of Health, National Cancer Institute.
NR 45
TC 1
Z9 1
U1 4
U2 4
PU IMPACT JOURNALS LLC
PI ALBANY
PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA
SN 1949-2553
J9 ONCOTARGET
JI Oncotarget
PD NOV 22
PY 2016
VL 7
IS 47
BP 77365
EP 77377
DI 10.18632/oncotarget.12670
PG 13
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA EE5GK
UT WOS:000389633400084
PM 27764801
ER
PT J
AU Zhang, SH
He, L
Dai, N
Guan, W
Shan, JL
Yang, XQ
Zhong, ZY
Qing, Y
Jin, F
Chen, C
Yang, YX
Wang, HY
Baugh, L
Tell, G
Wilson, DM
Li, MX
Wang, D
AF Zhang, Shiheng
He, Le
Dai, Nan
Guan, Wei
Shan, Jinlu
Yang, Xueqin
Zhong, Zhaoyang
Qing, Yi
Jin, Feng
Chen, Chuan
Yang, Yuxin
Wang, Hongyi
Baugh, Laura
Tell, Gianluca
Wilson, David M., III
Li, Mengxia
Wang, Dong
TI Serum APE1 as a predictive marker for platinum-based chemotherapy of
non-small cell lung cancer patients
SO Oncotarget
LA English
DT Article
DE APE1; NSCLC; chemotherapy; biomarker
ID DNA-REPAIR; BREAST-CANCER; P53 PROTEIN; APE1/REF-1; ANTIBODIES;
EXPRESSION; BIOMARKER; ERCC1
AB Purpose: To define the role of the DNA repair protein apurinic/apyrimidinic endonuclease 1 (APE1) in predicting the prognosis and chemotherapeutic response of non-small cell lung cancer patients receiving platinum-containing chemotherapy. Results: Our investigations found that serum APE1 level was significantly elevated in 229 of 412 NSCLC patients and correlated with its level in tissue (r(2) = 0.639, p < 0.001). The elevated APE1 level in both tissue and serum of patients prior to chemotherapy was associated with worse progression-free survival (HR: 2.165, p < 0.001, HR: 1.421, p = 0.012), but not with overall survival. After 6 cycles of chemotherapy, a low APE1 serum level was associated with better overall survival (HR: 0.497, p = 0.010).
Experimental Design: We measured APE1 protein levels in biopsy tissue from 172 NSCLC patients and sera of 412 NSCLC patients receiving platinum-based chemotherapy by immunohistochemistry and a newly established sensitive and specific enzyme-linked immunosorbent assay, respectively. APE1 levels in sera of 523 healthy donors were also determined as control.
Conclusions: Our studies indicate that APE1 is a biomarker for predicting prognosis and therapeutic efficacy in NSCLC. The chemotherapy-naIve serum APE1 level, which correlated with its tissue level inversely associated with progression-free survival of platinum-containing doublet chemotherapy, whereas post-treatment serum APE1 level was inversely associated with overall survival.
C1 [Zhang, Shiheng; He, Le; Dai, Nan; Guan, Wei; Shan, Jinlu; Yang, Xueqin; Zhong, Zhaoyang; Qing, Yi; Jin, Feng; Chen, Chuan; Yang, Yuxin; Li, Mengxia; Wang, Dong] Third Mil Med Univ, Daping Hosp, Inst Surg Res, Canc Ctr, Chongqing 400042, Peoples R China.
[Tell, Gianluca] Univ Udine, Dept Med & Biol Sci, Lab Mol Biol & DNA Repair, I-33100 Udine, Italy.
[Wilson, David M., III] NIA, Lab Mol Gerontol, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
[Wang, Hongyi; Baugh, Laura] Baylor Univ, Med Ctr, Dept Pathol, Dallas, TX 75246 USA.
Tianjin HUABOTE Biotechnol Inc, Tianjin 300350, Peoples R China.
RP Li, MX; Wang, D (reprint author), Third Mil Med Univ, Daping Hosp, Inst Surg Res, Canc Ctr, Chongqing 400042, Peoples R China.
EM mengxia.li@outlook.com; dongwang64@hotmail.com
FU Translational Research Grant from Third Military Medical University
[2013XZH01]; Health Care Grant from Health Department of General
Logistics Department [ZHBJ201465]; Intramural Research Program of the
NIH, National Institute on Aging; Associazione Italiana per la Ricerca
sul Cancro (AIRC) [IG14038, IG18400]
FX This work was supported by Translational Research Grant from Third
Military Medical University [2013XZH01] and Health Care Grant from
Health Department of General Logistics Department [ZHBJ201465] to Dr.
Dong Wang. This research was supported in part by the Intramural
Research Program of the NIH, National Institute on Aging to Dr. David
Wilson III. This research was supported in part by the Associazione
Italiana per la Ricerca sul Cancro (AIRC) to Prof Gianluca Tell (grants
# IG14038 and IG18400).
NR 25
TC 0
Z9 0
U1 1
U2 1
PU IMPACT JOURNALS LLC
PI ALBANY
PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA
SN 1949-2553
J9 ONCOTARGET
JI Oncotarget
PD NOV 22
PY 2016
VL 7
IS 47
BP 77482
EP 77494
DI 10.18632/oncotarget.13030
PG 13
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA EE5GK
UT WOS:000389633400093
PM 27813497
ER
PT J
AU Cook, MB
Drahos, J
Wood, S
Enewold, L
Parsons, R
Freedman, ND
Taylor, PR
Ricker, W
Abnet, CC
AF Cook, Michael B.
Drahos, Jennifer
Wood, Shannon
Enewold, Lindsey
Parsons, Ruth
Freedman, Neal D.
Taylor, Philip R.
Ricker, Winnie
Abnet, Christian C.
TI Pathogenesis and progression of oesophageal adenocarcinoma varies by
prior diagnosis of Barrett's oesophagus
SO BRITISH JOURNAL OF CANCER
LA English
DT Article
DE Barrett oesophagus; oesophageal neoplasms; Medicare; SEER program
ID CANCER; REFLUX; SENSITIVITY; ENDOSCOPY; SURVIVAL; TIME
AB Background: The absolute risk of oesophageal adenocarcinoma (EA) among individuals with Barrett's oesophagus (BE) is low and a majority of EA cases are diagnosed among individuals with no prior BE diagnosis. To ensure that insights from EA case-control studies are transferable to clinical management of BE populations, we conducted a case-case study to compare the clinical presentation, medical history and survival of EA cases with and without a prior BE diagnosis in the Surveillance, Epidemiology and End Results Medicare database.
Methods: Eligible EA cases were diagnosed at age >= 68 years during 1994-2009. There were 5271 EA cases in this study, 87% of which did not have a prior diagnosis of BE (EA-no prior BE).
Results: Multivariable case-case comparisons evidenced adverse associations of GERD, ever cigarette smoking, hypertension, dyslipidemia, weight loss, peptic ulcer and irritable bowel disease each in EA-prior BE compared with EA-no prior BE. Obesity, metabolic syndrome, impaired fasting glucose and diabetes did not differ between groups. EA-prior BE cases were diagnosed with less advanced disease, were more likely to undergo surgery and less likely to receive chemotherapy and radiotherapy, and had better overall mean survival (2.5 vs 1.4 years). This survival advantage persisted in the multivariable Cox model (HR = 0.69, 95% CI: 0.60, 0.78), despite adjustment for many factors including stage, grade and clinical interventions.
Conclusions: This study provides evidence that EA cases occurring among individuals previously diagnosed with BE are different from the large majority of EA cases that occur without a prior BE diagnosis. Regardless of whether these differences emanate from aetiology, biology and/or selection biases, they underscore the importance of a prudent approach in using knowledge from EAC case-control studies in the management of BE populations.
C1 [Cook, Michael B.; Drahos, Jennifer; Wood, Shannon; Freedman, Neal D.; Taylor, Philip R.; Abnet, Christian C.] NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Rockville, MD 20850 USA.
[Enewold, Lindsey] NCI, Div Canc Control & Populat Sci, NIH, DHHS, Rockville, MD 20850 USA.
[Parsons, Ruth; Ricker, Winnie] Informat Management Serv Inc, Rockville, MD 20852 USA.
RP Cook, MB (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Rockville, MD 20850 USA.
EM michael.cook@nih.gov
RI Abnet, Christian/C-4111-2015
OI Abnet, Christian/0000-0002-3008-7843
NR 18
TC 0
Z9 0
U1 3
U2 3
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 NOV 22
PY 2016
VL 115
IS 11
BP 1383
EP 1390
DI 10.1038/bjc.2016.344
PG 8
WC Oncology
SC Oncology
GA ED2ZP
UT WOS:000388719100016
PM 27780192
ER
PT J
AU Bjorge, T
Gissler, M
Ording, AG
Engeland, A
Glimelius, I
Leinonen, M
Sorensen, HT
Tretli, S
Ekbom, A
Troisi, R
Grotmol, T
AF Bjorge, Tone
Gissler, Mika
Ording, Anne Gulbech
Engeland, Anders
Glimelius, Ingrid
Leinonen, Maarit
Sorensen, Henrik Toft
Tretli, Steinar
Ekbom, Anders
Troisi, Rebecca
Grotmol, Tom
TI Reproductive history and risk of colorectal adenocarcinoma in parous
women: a Nordic population-based case-control study
SO BRITISH JOURNAL OF CANCER
LA English
DT Article
DE colorectal cancer; reproductive history; case-control study; Nordic
countries
ID CANCER-RISK; COLON-CANCER; POSTMENOPAUSAL WOMEN; ORAL-CONTRACEPTIVES;
QUALITY-CONTROL; METAANALYSIS; REGISTRY; COMPLETENESS; ASPIRIN; BETA
AB Background: Data are conflicting regarding the role of endogenous sex hormones in colorectal carcinogenesis. In this large population-based study, we pooled data from birth and cancer registries in four Nordic countries, to evaluate the risk of colorectal adenocarcinoma in relation to women's reproductive history.
Methods: We conducted a population-based case-control study among women registered in Nordic birth registries. The study included colorectal adenocarcinoma cases diagnosed in Denmark, Finland, Norway, and Sweden during 1967-2013 and up to 10 matched controls per case, in total 22 185 cases and 220 246 controls. Odds ratios (ORs) with 95% confidence intervals (95% CIs) were derived from conditional logistic regression models. We had limited information available on possible confounders.
Results: We found no evidence for associations between colorectal adenocarcinoma and parity, age at first and last birth, and time since first and last birth. The risk estimates were also close to unity for specific cancer subsites (proximal and distal colon and rectum). As well, when the analyses were stratified on menopausal status, parity, and mother's year of birth, no indication of associations was found.
Conclusions: In this large, Nordic population-based study, no evidence for associations was found between women's reproductive history and colorectal adenocarcinoma in parous women.
C1 [Bjorge, Tone; Engeland, Anders] Univ Bergen, Dept Global Publ Hlth & Primary Care, Bergen, Norway.
[Bjorge, Tone; Tretli, Steinar; Grotmol, Tom] Canc Registry Norway, Oslo, Norway.
[Gissler, Mika] Natl Inst Hlth & Welf THL, Helsinki, Finland.
[Ording, Anne Gulbech; Sorensen, Henrik Toft] Aarhus Univ Hosp, Dept Clin Epidemiol, Aarhus, Denmark.
[Engeland, Anders] Norwegian Inst Publ Hlth, Dept Pharmacoepidemiol, Div Mental & Phys Hlth, Bergen, Norway.
[Glimelius, Ingrid; Ekbom, Anders] Karolinska Inst, Clin Epidemiol Unit, Dept Med, Stockholm, Sweden.
[Glimelius, Ingrid; Ekbom, Anders] Karolinska Univ Hosp, Stockholm, Sweden.
[Glimelius, Ingrid] Uppsala Univ, Dept Immunol Genet & Pathol, Uppsala, Sweden.
[Leinonen, Maarit] Finnish Canc Registry, Canc Soc Finland, Helsinki, Finland.
[Troisi, Rebecca] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD USA.
RP Bjorge, T (reprint author), Univ Bergen, Dept Global Publ Hlth & Primary Care, Bergen, Norway.; Bjorge, T (reprint author), Canc Registry Norway, Oslo, Norway.
EM Tone.Bjorge@uib.no
OI Glimelius, Ingrid/0000-0001-6158-3041
FU Nordic Cancer Union; Program for Clinical Research Infrastructure
(PROCRIN); Novo Nordisk Foundation; Danish Cancer Society; Svenska
Sallskapet for Medicinsk Forskning (SSMF); Svenska Lakarsallskapet; U.S.
National Cancer Institute, National Institutes of Health, Department of
Health and Human Services
FX This study was supported by the Nordic Cancer Union, Program for
Clinical Research Infrastructure (PROCRIN) established by the Lundbeck
Foundation and the Novo Nordisk Foundation, Danish Cancer Society,
Svenska Sallskapet for Medicinsk Forskning (SSMF), Svenska
Lakarsallskapet, and the U.S. National Cancer Institute, National
Institutes of Health, Department of Health and Human Services.
NR 38
TC 0
Z9 0
U1 4
U2 4
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 NOV 22
PY 2016
VL 115
IS 11
BP 1416
EP 1420
DI 10.1038/bjc.2016.315
PG 5
WC Oncology
SC Oncology
GA ED2ZP
UT WOS:000388719100020
PM 27701386
ER
PT J
AU Yang, ZH
Emma-Okon, B
Remaley, AT
AF Yang, Zhi-Hong
Emma-Okon, Beatrice
Remaley, Alan T.
TI Dietary marine-derived long-chain monounsaturated fatty acids and
cardiovascular disease risk: a mini review
SO LIPIDS IN HEALTH AND DISEASE
LA English
DT Review
DE Long-chain monounsaturated fatty acids; Cardiovascular disease;
Atherosclerosis; Peroxisome proliferator-activated receptor signaling
pathway; Inflammation
ID E-DEFICIENT MICE; SEAL OIL; EICOSAPENTAENOIC ACID; METABOLICALLY
HEALTHY; LIPID-COMPOSITION; PARAOXONASE 1; LIVER LIPIDS; PPAR-GAMMA;
FISH-OIL; PLASMA
AB Regular fish/fish oil consumption is widely recommended for protection against cardiovascular diseases (CVD). Fish and other marine life are rich sources of the cardioprotective long-chain n-3 polyunsaturated fatty acids (n-3 PUFA) eicosapentaenoic acid (C20:5 n-3; EPA) and docosahexaenoic acid (C22:6 n-3; DHA). The lipid content and fatty acid profile of fish, however, vary greatly among different fish species. In addition to n-3 PUFA, certain fish, such as saury, pollock, and herring, also contain high levels of long-chain monounsaturated fatty acids (LCMUFA), with aliphatic tails longer than 18 C atoms (i.e., C20:1 and C22:1 isomers). Compared with well-studied n-3 PUFA, limited information, however, is available on the health benefits of marine-derived LCMUFA, particularly in regard to CVD. Our objective in this review is to summarize the current knowledge and provide perspective on the potential therapeutic value of dietary LCMUFA-rich marine oil for improving CVD risk factors. We will also review the possible mechanisms of LCMUFA action on target tissues. Finally, we describe the epidemiologic data and small-scaled clinical studies that have been done on marine oils enriched in LCMUFA. Although there are still many unanswered questions about LCMUFA, this appears to be promising new area of research that may lead to new insights into the health benefits of a different component of fish oils besides n-3 PUFA.
C1 [Yang, Zhi-Hong; Emma-Okon, Beatrice; Remaley, Alan T.] NHLBI, Lipoprotein Metab Sect, Cardiopulm Branch, NIH, Bldg 10, Bethesda, MD 20892 USA.
[Yang, Zhi-Hong] Nippon Suisan Kaisha, Tokyo Innovat Ctr, Cent Res Lab, 32-3 Nanakuni 1 Chome Hachioji, Tokyo 1920991, Japan.
RP Remaley, AT (reprint author), NHLBI, Lipoprotein Metab Sect, Cardiopulm Branch, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM aremaley1@nhlbi.nih.gov
FU Intramural Research Program of the National Heart, Lung and Blood
Institute (NHLBI); Office of Dietary Supplements (ODS) Research Scholars
Program at National Institutes of Health
FX The authors acknowledge financial support by the Intramural Research
Program of the National Heart, Lung and Blood Institute (NHLBI) and the
Office of Dietary Supplements (ODS) Research Scholars Program at
National Institutes of Health.
NR 75
TC 0
Z9 0
U1 6
U2 6
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1476-511X
J9 LIPIDS HEALTH DIS
JI Lipids Health Dis.
PD NOV 22
PY 2016
VL 15
AR 201
DI 10.1186/s12944-016-0366-5
PG 9
WC Biochemistry & Molecular Biology; Nutrition & Dietetics
SC Biochemistry & Molecular Biology; Nutrition & Dietetics
GA ED3TB
UT WOS:000388770300001
PM 27876051
ER
PT J
AU Bang, A
Patel, A
Bellad, R
Gisore, P
Goudar, SS
Esamai, F
Liechty, EA
Meleth, S
Goco, N
Niermeyer, S
Keenan, W
Kamath-Rayne, BD
Little, GA
Clarke, SB
Flanagan, VA
Bucher, S
Jain, M
Mujawar, N
Jain, V
Rukunga, J
Mahantshetti, N
Dhaded, S
Bhandankar, M
McClure, EM
Carlo, WA
Wright, LL
Hibberd, PL
AF Bang, Akash
Patel, Archana
Bellad, Roopa
Gisore, Peter
Goudar, Shivaprasad S.
Esamai, Fabian
Liechty, Edward A.
Meleth, Sreelatha
Goco, Norman
Niermeyer, Susan
Keenan, William
Kamath-Rayne, Beena D.
Little, George A.
Clarke, Susan B.
Flanagan, Victoria A.
Bucher, Sherri
Jain, Manish
Mujawar, Nilofer
Jain, Vinita
Rukunga, Janet
Mahantshetti, Niranjana
Dhaded, Sangappa
Bhandankar, Manisha
McClure, Elizabeth M.
Carlo, Waldemar A.
Wright, Linda L.
Hibberd, Patricia L.
TI Helping Babies Breathe (HBB) training: What happens to knowledge and
skills over time?
SO BMC PREGNANCY AND CHILDBIRTH
LA English
DT Article
DE Helping Babies Breathe; Resuscitation; Bag and mask ventilation;
Perinatal mortality; Asphyxia; Stillbirth; Training
ID EMERGENCY CARDIOVASCULAR CARE; NEONATAL RESUSCITATION;
CARDIOPULMONARY-RESUSCITATION; NEWBORN MORTALITY; SAVE LIVES; SCALE-UP;
COUNTRIES; DEATHS; PERFORMANCE; STILLBIRTH
AB Background: The first minutes after birth are critical to reducing neonatal mortality. Helping Babies Breathe (HBB) is a simulation-based neonatal resuscitation program for low resource settings. We studied the impact of initial HBB training followed by refresher training on the knowledge and skills of the birth attendants in facilities.
Methods: We conducted HBB trainings in 71 facilities in the NICHD Global Network research sites (Nagpur and Belgaum, India and Eldoret, Kenya), with a 6: 1 ratio of facility trainees to Master Trainers (MT). Because of staff turnover, some birth attendants (BA) were trained as they joined the delivery room staff, after the initial training was completed (catch-up initial training). We compared pass rates for skills and knowledge pre- and post-initial HBB training and following refresher training among active BAs. An Objective Structured Clinical Examination (OSCE) B tested resuscitation skill retention by comparing post-initial training performance with pre-refresher training performance. We identified factors associated with loss of skills in pre-refresher training performance using multivariable logistic regression analysis. Daily bag and mask ventilation practice, equipment checks and supportive supervision were stressed as part of training.
Results: One hundred five MT (1.6 MT per facility) conducted initial and refresher HBB trainings for 835 BAs; 76% had no prior resuscitation training. Initial training improved knowledge and skills: the pass percentage for knowledge tests improved from 74 to 99% (p < 0.001). Only 5% could ventilate a newborn mannequin correctly before initial training but 97% passed the post-initial ventilation training test (p < 0.0001) and 99% passed the OSCE B resuscitation evaluation. During pre-refresher training evaluation, a mean of 6.7 (SD 2.49) months after the initial training, 99% passed the knowledge test, but the successful completion rate fell to 81% for the OSCE B resuscitation skills test. Characteristics associated with deterioration of resuscitation skills were BAs from tertiary care facilities, no prior resuscitation training, and the timing of training (initial vs. catch-up training).
Conclusions: HBB training significantly improved neonatal resuscitation knowledge and skills. However, skills declined more than knowledge over time. Ongoing skills practice and monitoring, more frequent retesting, and refresher trainings are needed to maintain neonatal resuscitation skills.
C1 [Bang, Akash; Jain, Manish] Mahatma Gandhi Inst Med Sci, Sevagram, India.
[Patel, Archana] Lata Med Res Fdn, Nagpur, Maharashtra, India.
[Bellad, Roopa; Goudar, Shivaprasad S.; Mahantshetti, Niranjana; Dhaded, Sangappa; Bhandankar, Manisha] KLE Univ, JN Med Coll, Belgaum, India.
[Gisore, Peter; Esamai, Fabian; Rukunga, Janet] Moi Univ, Moi Teaching & Referral Hosp, Eldoret, Kenya.
[Liechty, Edward A.; Bucher, Sherri] Indiana Univ Sch Med, Indianapolis, IN 46202 USA.
[Meleth, Sreelatha; Goco, Norman; McClure, Elizabeth M.] RTI Int, Durham, NC USA.
[Niermeyer, Susan] Univ Colorado, Sch Med, Aurora, CO USA.
[Keenan, William] St Louis Univ, St Louis, MO 63103 USA.
[Kamath-Rayne, Beena D.] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45229 USA.
[Little, George A.; Flanagan, Victoria A.] Geisel Sch Med Dartmouth, Lebanon, NH USA.
[Clarke, Susan B.] Childrens Hosp Colorado, Aurora, CO USA.
[Mujawar, Nilofer] NKP Salve Inst Med Sci, Nagpur, Maharashtra, India.
[Jain, Vinita] Daga Mem Govt Womens Hosp, Nagpur, Maharashtra, India.
[Carlo, Waldemar A.] Univ Alabama Birmingham, Birmingham, AL USA.
[Wright, Linda L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD 20892 USA.
[Wright, Linda L.] George Washington Univ, 5800 Nicholson Lane,1206, Rockville, MD 20852 USA.
[Hibberd, Patricia L.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Wright, LL (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD 20892 USA.; Wright, LL (reprint author), George Washington Univ, 5800 Nicholson Lane,1206, Rockville, MD 20852 USA.
EM lindawright.md@gmail.com
FU Laerdal Foundation; Norwegian Agency for Development Cooperation
(Norad); NICHD [U01 HD040636, U01 HD058322, U10 HD078439, HD U01058326,
U01 HD058326-04S1, U10 HD076461, U01 HD042372, U10 HD076457]
FX This study was funded with grants from the Laerdal Foundation, Norwegian
Agency for Development Cooperation (Norad), and the NICHD (grant numbers
U01 HD040636; U01 HD058322 and U10 HD078439; HD U01058326; U01
HD058326-04S1, U10 HD076461, U01 HD042372, U10 HD076457).
NR 33
TC 0
Z9 0
U1 2
U2 2
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2393
J9 BMC PREGNANCY CHILDB
JI BMC Pregnancy Childbirth
PD NOV 22
PY 2016
VL 16
AR 364
DI 10.1186/s12884-016-1141-3
PG 12
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA EC8XU
UT WOS:000388427200002
PM 27875999
ER
PT J
AU Kavousi, M
Desai, CS
Ayers, C
Blumenthal, RS
Budoff, MJ
Mahabadi, AA
Ikram, MA
van der Lugt, A
Hofman, A
Erbel, R
Khera, A
Geisel, MH
Jockel, KH
Lehmann, N
Hoffmann, U
O'Donnell, CJ
Massaro, JM
Liu, K
Mohlenkamp, S
Ning, HY
Franco, OH
Greenland, P
AF Kavousi, Maryam
Desai, Chintan S.
Ayers, Colby
Blumenthal, Roger S.
Budoff, Matthew J.
Mahabadi, Amir-Abbas
Ikram, M. Arfan
van der Lugt, Aad
Hofman, Albert
Erbel, Raimund
Khera, Amit
Geisel, Marie H.
Joeckel, Karl-Heinz
Lehmann, Nils
Hoffmann, Udo
O'Donnell, Christopher J.
Massaro, Joseph M.
Liu, Kiang
Moehlenkamp, Stefan
Ning, Hongyan
Franco, Oscar H.
Greenland, Philip
TI Prevalence and Prognostic Implications of Coronary Artery Calcification
in Low-Risk Women A Meta-analysis
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Article
ID HEART-DISEASE; CARDIOVASCULAR-DISEASE; STATIN THERAPY; CALCIUM SCORE;
PREDICTION; DESIGN; CLASSIFICATION; INDIVIDUALS; PREVENTION; MARKERS
AB IMPORTANCE The role of coronary artery calcium (CAC) testing for guiding preventive strategies among women at low cardiovascular disease (CVD) risk based on the American College of Cardiology and American Heart Association CVD prevention guidelines is unclear.
OBJECTIVE To assess the potential utility of CAC testing for CVD risk estimation and stratification among low-risk women.
DESIGN, SETTING, AND PARTICIPANTS Women with 10-year atherosclerotic CVD (ASCVD) risk lower than 7.5% from 5 large population-based cohorts: the Dallas Heart Study (United States), the Framingham Heart Study (United States), the Heinz Nixdorf Recall study (Germany), the Multi-Ethnic Study of Atherosclerosis (United States), and the Rotterdam Study (the Netherlands). The 5 cohorts were selected based on the availability of CAC data in a sizable group of low-risk women from the general population together with the long detailed follow-up data. Across the cohorts, events were assessed from the date of CAC scan (performed from 1998 through 2006) until January 1, 2012; January 1, 2014; or March 6, 2015. Fixed-effects meta-analysis was conducted to combine the results of the 5 studies.
EXPOSURES CAC score by computed tomography.
MAIN OUTCOMES AND MEASURES Main outcome was incident ASCVD, including nonfatal myocardial infarction, coronary heart disease (CHD) death, and stroke. Association of CAC with ASCVD was examined using Cox proportional hazards models. To assess whether CAC was associated with improved ASCVD risk predictions beyond the traditional risk factors, the C statistic and the continuous net reclassification improvement (cNRI) index were calculated.
RESULTS Among 6739 women with low ASCVD risk from the 5 studies, mean age ranged from 44 to 63 years and CAC was present in 36.1%. Across the cohorts, median follow-up ranged from 7.0 to 11.6 years. A total of 165 ASCVD events occurred (64 nonfatal myocardial infarctions, 29 CHD deaths, and 72 strokes), with the ASCVD incidence rates ranging from 1.5 to 6.0 per 1000 person-years. Compared with the absence of CAC (CAC = 0), presence of CAC (CAC > 0) was associated with an increased risk of ASCVD (incidence rates per 1000 person-years, 1.41 for CAC absence vs 4.33 for CAC presence; difference, 2.92 [95% CI, 2.02-3.83]; multivariable-adjusted hazard ratio, 2.04 [95% CI, 1.44-2.90]). The addition of CAC to traditional risk factors improved the C statistic from 0.73 (95% CI, 0.69-0.77) to 0.77 (95% CI, 0.74-0.81) and provided a cNRI of 0.20 (95% CI, 0.09-0.31) for ASCVD prediction.
CONCLUSIONS AND RELEVANCE Among women at low ASCVD risk, CAC was present in approximately one-third and was associated with an increased risk of ASCVD and modest improvement in prognostic accuracy compared with traditional risk factors. Further research is needed to assess the clinical utility and cost-effectiveness of this additional accuracy.
C1 [Kavousi, Maryam; Ikram, M. Arfan; Hofman, Albert; Franco, Oscar H.] Erasmus Univ, Med Ctr, Dept Epidemiol, Off Na 2906,POB 2040, NL-3000 CA Rotterdam, Netherlands.
[Desai, Chintan S.; Blumenthal, Roger S.] Johns Hopkins Med Inst, Div Cardiol, Ciccarone Ctr Prevent Heart Dis, Baltimore, MD 21205 USA.
[Ayers, Colby] Univ Texas Southwestern Med Ctr Dallas, Div Clin Sci, Dallas, TX 75390 USA.
[Budoff, Matthew J.] Harbor Univ Calif Los Angeles Med Ctr, Los Angeles Biomed Res Inst, Div Cardiol, Los Angeles, CA USA.
[Mahabadi, Amir-Abbas] Univ Clin Essen, West German Heart & Vasc Ctr, Dept Cardiol, Essen, Germany.
[Ikram, M. Arfan; van der Lugt, Aad] Erasmus Univ, Med Ctr, Dept Radiol, Rotterdam, Netherlands.
[Ikram, M. Arfan] Erasmus Univ, Med Ctr, Dept Neurol, Rotterdam, Netherlands.
[Hofman, Albert] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.
[Erbel, Raimund; Geisel, Marie H.; Joeckel, Karl-Heinz; Lehmann, Nils] Univ Duisburg Essen, Inst Med Informat Biometry & Epidemiol, Essen, Germany.
[Khera, Amit] Univ Texas Southwestern Med Ctr Dallas, Div Cardiol, Dallas, TX 75390 USA.
[Hoffmann, Udo] Massachusetts Gen Hosp, Cardiac MR PET CT Program, Dept Radiol, Boston, MA 02114 USA.
[Hoffmann, Udo] Harvard Med Sch, Boston, MA USA.
[O'Donnell, Christopher J.] Harvard Med Sch, Massachusetts Gen Hosp, Div Cardiol, Dept Med, Boston, MA USA.
[O'Donnell, Christopher J.; Massaro, Joseph M.] NHLBI, Framingham Heart Study, Framingham, MA USA.
[O'Donnell, Christopher J.] NHLBI, Bldg 10, Bethesda, MD 20892 USA.
[Massaro, Joseph M.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Liu, Kiang; Ning, Hongyan; Greenland, Philip] Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, Chicago, IL 60611 USA.
[Moehlenkamp, Stefan] Krankenhaus Bethanien, Dept Cardiol, Moers, Germany.
RP Kavousi, M (reprint author), Erasmus Univ, Med Ctr, Dept Epidemiol, Off Na 2906,POB 2040, NL-3000 CA Rotterdam, Netherlands.
EM m.kavousi@erasmusmc.nl
FU NCATS NIH HHS [UL1 TR000040, UL1 TR001105]; NHLBI NIH HHS [R01 HL076784,
N01 HC025195, R01 HL060040, R01 HL070100, R01 HL071039, R01 HL077447,
R01 HL080124, R01 HL107385]; NIA NIH HHS [R01 AG028321]
NR 34
TC 1
Z9 1
U1 3
U2 3
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 NOV 22
PY 2016
VL 316
IS 20
BP 2126
EP 2134
DI 10.1001/jama.2016.17020
PG 9
WC Medicine, General & Internal
SC General & Internal Medicine
GA ED1XD
UT WOS:000388637300020
PM 27846641
ER
PT J
AU Cook, PR
Tabor, GT
AF Cook, Pamela R.
Tabor, G. Travis
TI Deciphering fact from artifact when using reporter assays to investigate
the roles of host factors on L1 retrotransposition
SO MOBILE DNA
LA English
DT Article
DE L1; LINE-1; Reporter; Host factor; p38; HSV-TK; SV40; Promoter; Renilla
ID MAP KINASE ISOFORMS; GENE-EXPRESSION; SOMATIC RETROTRANSPOSITION;
CYTOMEGALOVIRUS PROMOTER; ALU RETROTRANSPOSITION; TRANSPOSABLE ELEMENTS;
SELECTIVE ACTIVATION; RENILLA LUCIFERASE; NERVOUS-SYSTEM; CANCER-THERAPY
AB Background: The Long INterspersed Element-1 (L1, LINE-1) is the only autonomous mobile DNA element in humans and has generated as much as half of the genome. Due to increasing clinical interest in the roles of L1 in cancer, embryogenesis and neuronal development, it has become a priority to understand L1-host interactions and identify host factors required for its activity. Apropos to this, we recently reported that L1 retrotransposition in HeLa cells requires phosphorylation of the L1 protein ORF1p at motifs targeted by host cell proline-directed protein kinases (PDPKs), which include the family of mitogen-activated protein kinases (MAPKs). Using two engineered L1 reporter assays, we continued our investigation into the roles of MAPKs in L1 activity.
Results: We found that the MAPK p38 delta phosphorylated ORF1p on three of its four PDPK motifs required for L1 activity. In addition, we found that a constitutively active p38d mutant appeared to promote L1 retrotransposition in HeLa cells. However, despite the consistency of these findings with our earlier work, we identified some technical concerns regarding the experimental methodology. Specifically, we found that exogenous expression of p38d appeared to affect at least one heterologous promoter in an engineered L1 reporter, as well as generate opposing effects on two different reporters. We also show that two commercially available non-targeting control (NTC) siRNAs elicit drastically different effects on the apparent retrotransposition reported by both L1 assays, which raises concerns about the use of NTCs as normalizing controls.
Conclusions: Engineered L1 reporter assays have been invaluable for determining the functions and critical residues of L1 open reading frames, as well as elucidating many aspects of L1 replication. However, our results suggest that caution is required when interpreting data obtained from L1 reporters used in conjunction with exogenous gene expression or siRNA.
C1 [Cook, Pamela R.] NIDDK, Lab Cell & Mol Biol, NIH, 8 Ctr Dr, Bethesda, MD 20892 USA.
[Tabor, G. Travis] NICHHD, NIH, 35 Convent Dr, Bethesda, MD 20892 USA.
RP Cook, PR (reprint author), NIDDK, Lab Cell & Mol Biol, NIH, 8 Ctr Dr, Bethesda, MD 20892 USA.
EM pamela.cook@nih.gov
FU laboratory of Anthony V. Furano at the National Institute of Diabetes
and Digestive and Kidney Diseases, National Institutes of Health
[1-ZIA-DK057601-19]
FX This work was supported by the laboratory of Anthony V. Furano at the
National Institute of Diabetes and Digestive and Kidney Diseases,
National Institutes of Health; Grant 1-ZIA-DK057601-19.
NR 95
TC 0
Z9 0
U1 1
U2 1
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1759-8753
J9 MOBILE DNA-UK
JI Mob. DNA
PD NOV 22
PY 2016
VL 7
AR 23
DI 10.1186/s13100-016-0079-3
PG 15
WC Genetics & Heredity
SC Genetics & Heredity
GA ED0CP
UT WOS:000388510900001
PM 27895722
ER
PT J
AU Lam, KH
Li, Y
Li, Y
Lim, HG
Zhou, QF
Shung, KK
AF Lam, Kwok Ho
Li, Ying
Li, Yang
Lim, Hae Gyun
Zhou, Qifa
Shung, Koping Kirk
TI Multifunctional single beam acoustic tweezer for non-invasive
cell/organism manipulation and tissue imaging
SO SCIENTIFIC REPORTS
LA English
DT Article
ID ULTRASONIC TRANSDUCERS; CELLS; FORCE
AB Non-contact precise manipulation of single microparticles, cells, and organisms has attracted considerable interest in biophysics and biomedical engineering. Similar to optical tweezers, acoustic tweezers have been proposed to be capable of manipulating microparticles and even cells. Although there have been concerted efforts to develop tools for non-contact manipulation, no alternative to complex, unifunctional tweezer has yet been found. Here we report a simple, low-cost, multifunctional single beam acoustic tweezer (SBAT) that is capable of manipulating an individual micrometer scale non-spherical cell at Rayleigh regime and even a single millimeter scale organism at Mie regime, and imaging tissue as well. We experimentally demonstrate that the SBAT with an ultralow f-number (f# = focal length/aperture size) could manipulate an individual red blood cell and a single 1.6 mm-diameter fertilized Zebrafish egg, respectively. Besides, in vitro rat aorta images were collected successfully at dynamic foci in which the lumen and the outer surface of the aorta could be clearly seen. With the ultralow f-number, the SBAT offers the combination of large acoustic radiation force and narrow beam width, leading to strong trapping and high-resolution imaging capabilities. These attributes enable the feasibility of using a single acoustic device to perform non-invasive multi-functions simultaneously for biomedical and biophysical applications.
C1 [Lam, Kwok Ho] Hong Kong Polytech Univ, Dept Elect Engn, Hong Kong, Hong Kong, Peoples R China.
[Li, Ying; Li, Yang; Lim, Hae Gyun; Zhou, Qifa; Shung, Koping Kirk] Univ So Calif, NIH Transducer Resource Ctr, Los Angeles, CA 90089 USA.
[Li, Ying; Li, Yang; Lim, Hae Gyun; Zhou, Qifa; Shung, Koping Kirk] Univ So Calif, Dept Biomed Engn, Los Angeles, CA 90089 USA.
RP Lam, KH (reprint author), Hong Kong Polytech Univ, Dept Elect Engn, Hong Kong, Hong Kong, Peoples R China.
EM kokokh.lam@polyu.edu.hk
RI Lam, K.H./B-7765-2014
OI Lam, K.H./0000-0003-1456-9049
FU Hong Kong Research Grants Council (ECS Grant) [253001/14 P]; Hong Kong
Polytechnic University [4-ZZDC, 1-ZVCG, G-YBLM]; NIH [R01-EB12058,
P41-EB02182]
FX We thank Young-Kwon Hong for providing the rat aorta tissue sample; and
Yao-Sheng Tung for developing the imaging software. K.H.L. acknowledges
support from the Hong Kong Research Grants Council (ECS Grant No.
253001/14 P) and The Hong Kong Polytechnic University (Grant Nos 4-ZZDC,
1-ZVCG, and G-YBLM). K.K.S. acknowledges support from NIH Grant Nos
R01-EB12058 and P41-EB02182.
NR 23
TC 0
Z9 0
U1 14
U2 14
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 NOV 22
PY 2016
VL 6
AR 37554
DI 10.1038/srep37554
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EC6RI
UT WOS:000388263700001
PM 27874052
ER
PT J
AU Krey, JF
Krystofiak, ES
Dumont, RA
Vijayakumar, S
Choi, D
Rivero, F
Kachar, B
Jones, SM
Barr-Gillespie, PG
AF Krey, Jocelyn F.
Krystofiak, Evan S.
Dumont, Rachel A.
Vijayakumar, Sarath
Choi, Dongseok
Rivero, Francisco
Kachar, Bechara
Jones, Sherri M.
Barr-Gillespie, Peter G.
TI Plastin 1 widens stereocilia by transforming actin filament packing from
hexagonal to liquid
SO JOURNAL OF CELL BIOLOGY
LA English
DT Article
ID HAIR-CELL STEREOCILIA; CUTICULAR PLATE; BIRD COCHLEA; HEARING-LOSS;
F-ACTIN; MOUSE STRAINS; CROSS-LINKER; PROTEINS; ESPIN; ORGANIZATION
AB With their essential role in inner ear function, stereocilia of sensory hair cells demonstrate the importance of cellular actin protrusions. Actin packing in stereocilia is mediated by cross-linkers of the plastin, fascin, and espin families. Although mice lacking espin (ESPN) have no vestibular or auditory function, we found that mice that either lacked plastin 1 (PLS1) or had nonfunctional fascin 2 (FSCN2) had reduced inner ear function, with double-mutant mice most strongly affected. Targeted mass spectrometry indicated that PLS1 was the most abundant cross-linker in vestibular stereocilia and the second most abundant protein overall; ESPN only accounted for similar to 15% of the total cross-linkers in bundles. Mouse utricle stereocilia lacking PLS1 were shorter and thinner than wild-type stereocilia. Surprisingly, although wild-type stereocilia had random liquid packing of their actin filaments, stereocilia lacking PLS1 had orderly hexagonal packing. Although all three cross-linkers are required for stereocilia structure and function, PLS1 biases actin toward liquid packing, which allows stereocilia to grow to a greater diameter.
C1 [Krey, Jocelyn F.; Dumont, Rachel A.; Barr-Gillespie, Peter G.] Oregon Hlth & Sci Univ, Oregon Hearing Res Ctr, Portland, OR 97239 USA.
[Krey, Jocelyn F.; Dumont, Rachel A.; Barr-Gillespie, Peter G.] Oregon Hlth & Sci Univ, Vollum Inst, Portland, OR 97239 USA.
[Choi, Dongseok] Oregon Hlth & Sci Univ, Oregon Hlth & Sci Univ Portland State Univ Sch Pu, Portland, OR 97239 USA.
[Krystofiak, Evan S.; Kachar, Bechara] NIDCD, Lab Cell Struct & Dynam, NIH, Bethesda, MD 20892 USA.
[Vijayakumar, Sarath; Jones, Sherri M.] Univ Nebraska, Dept Special Educ & Commun Disorders, Lincoln, NE 68583 USA.
[Choi, Dongseok] Kyung Hee Univ, Grad Sch Dent, Seoul 02447, South Korea.
[Rivero, Francisco] Univ Hull, Hull York Med Sch, Ctr Cardiovasc & Metab Res, Kingston Upon Hull HU6 7RX, N Humberside, England.
RP Barr-Gillespie, PG (reprint author), Oregon Hlth & Sci Univ, Oregon Hearing Res Ctr, Portland, OR 97239 USA.; Barr-Gillespie, PG (reprint author), Oregon Hlth & Sci Univ, Vollum Inst, Portland, OR 97239 USA.
EM gillespp@ohsu.edu
OI Barr-Gillespie, Peter/0000-0002-9787-5860; Rivero,
Francisco/0000-0001-5435-6991; Choi, Dongseok/0000-0002-1552-4072;
Vijayakumar, Sarath/0000-0002-4652-2002
FU National Institutes of Health grants [R01 DC002368, R01 DC011034, P30
DC005983, F32 DC012455]; National Institute on Deafness and Other
Communication Disorders Intramural Research Program [Z01 DC000002];
Nebraska Tobacco Settlement Biomedical Research Development Fund
FX The work described here was supported by National Institutes of Health
grants R01 DC002368 (P.G. Barr-Gillespie), R01 DC011034 (P.G.
Barr-Gillespie), P30 DC005983 (P.G. Barr-Gillespie), and F32 DC012455
(J.F. Krey). E.S. Krystofiak and B. Kachar were supported by the
National Institute on Deafness and Other Communication Disorders
Intramural Research Program (Z01 DC000002). S.M. Jones was supported by
the Nebraska Tobacco Settlement Biomedical Research Development Fund. We
received support from the following core facilities: shotgun and
targeted MS from the Oregon Health and Science University (OHSU)
Proteomics Shared Resource, confocal and SIM from the OHSU Advanced
Light Microscopy Core at The Jungers Center, EM from the OHSU Multiscale
Microscopy Core, and EM from the National Institute on Deafness and
Other Communication Disorders Advanced Imaging Core (ZIC DC000081).
NR 60
TC 0
Z9 0
U1 2
U2 2
PU ROCKEFELLER UNIV PRESS
PI NEW YORK
PA 950 THIRD AVE, 2ND FLR, NEW YORK, NY 10022 USA
SN 0021-9525
EI 1540-8140
J9 J CELL BIOL
JI J. Cell Biol.
PD NOV 21
PY 2016
VL 215
IS 4
BP 467
EP 482
DI 10.1083/jcb.201606036
PG 16
WC Cell Biology
SC Cell Biology
GA ED2PT
UT WOS:000388690900007
PM 27811163
ER
PT J
AU Joshi, AS
Huang, XF
Choudhary, V
Levine, TP
Hu, JJ
Prinz, WA
AF Joshi, Amit S.
Huang, Xiaofang
Choudhary, Vineet
Levine, Tim P.
Hu, Junjie
Prinz, William A.
TI A family of membrane-shaping proteins at ER subdomains regulates
pre-peroxisomal vesicle biogenesis
SO JOURNAL OF CELL BIOLOGY
LA English
DT Article
ID TUBULAR ENDOPLASMIC-RETICULUM; SACCHAROMYCES-CEREVISIAE;
NUCLEAR-ENVELOPE; SELECTIVE AUTOPHAGY; NETWORK FORMATION; S. CEREVISIAE;
GTPASE SEY1P; CELLS; FORM; MECHANISMS
AB Saccharomyces cerevisiae contains three conserved reticulon and reticulon-like proteins that help maintain ER structure by stabilizing high membrane curvature in ER tubules and the edges of ER sheets. A mutant lacking all three proteins has dramatically altered ER morphology. We found that ER shape is restored in this mutant when Pex30p or its homologue Pex31p is overexpressed. Pex30p can tubulate membranes both in cells and when reconstituted into proteoliposomes, indicating that Pex30p is a novel ER-shaping protein. In contrast to the reticulons, Pex30p is low abundance, and we found that it localizes to subdomains in the ER. We show that these ER subdomains are the sites where most preperoxisomal vesicles (PPVs) are generated. In addition, overproduction or deletion of Pex30p or Pex31p alters the size, shape, and number of PPVs. Our findings suggest that Pex30p and Pex31p help shape and generate regions of the ER where PPV biogenesis occurs.
C1 [Joshi, Amit S.; Choudhary, Vineet; Prinz, William A.] NIDDK, Lab Cell & Mol Biol, NIH, Bethesda, MD 20892 USA.
[Huang, Xiaofang; Hu, Junjie] Nankai Univ, Dept Genet & Cell Biol, Coll Life Sci, Tianjin 300071, Peoples R China.
[Huang, Xiaofang; Hu, Junjie] Nankai Univ, Tianjin Key Lab Prot Sci, Tianjin 300071, Peoples R China.
[Levine, Tim P.] UCL, Inst Ophthalmol, London EC1V 9EL, England.
[Hu, Junjie] Chinese Acad Sci, Inst Biophys, Natl Lab Macromol, Beijing 100101, Peoples R China.
RP Prinz, WA (reprint author), NIDDK, Lab Cell & Mol Biol, NIH, Bethesda, MD 20892 USA.
EM prinzw@helix.nih.gov
OI HU, JUNJIE/0000-0003-4712-2243
FU Intramural Research Program of National Institute of Diabetes and
Digestive and Kidney Diseases; National Natural Science Foundation of
China [31225006]; International Early Career Scientist grant from Howard
Hughes Medical Institute; Biotechnology and Biological Sciences Research
Council Bioinformatics and Biological Resources Fund [BB/M011801];
Schweizerischer Nationalfonds zur Forderung der Wissenschaftlichen
Forschung [PA00P3_145358, P300P3_158454]
FX This work was supported by the Intramural Research Program of the
National Institute of Diabetes and Digestive and Kidney Diseases. J. Hu
was supported by the National Natural Science Foundation of China (grant
31225006) and an International Early Career Scientist grant from Howard
Hughes Medical Institute. T.P. Levine's laboratory was supported by the
Biotechnology and Biological Sciences Research Council Bioinformatics
and Biological Resources Fund (grant BB/M011801). V. Choudhary was
supported by a fellowship from Schweizerischer Nationalfonds zur
Forderung der Wissenschaftlichen Forschung (grants PA00P3_145358 and
P300P3_158454).
NR 49
TC 1
Z9 1
U1 4
U2 4
PU ROCKEFELLER UNIV PRESS
PI NEW YORK
PA 950 THIRD AVE, 2ND FLR, NEW YORK, NY 10022 USA
SN 0021-9525
EI 1540-8140
J9 J CELL BIOL
JI J. Cell Biol.
PD NOV 21
PY 2016
VL 215
IS 4
BP 515
EP 529
DI 10.1083/jcb.201602064
PG 15
WC Cell Biology
SC Cell Biology
GA ED2PT
UT WOS:000388690900010
PM 27872254
ER
PT J
AU McGowan, ML
Ponsaran, RS
Silverman, P
Harris, LN
Marshall, PA
AF McGowan, Michelle L.
Ponsaran, Roselle S.
Silverman, Paula
Harris, Lyndsay N.
Marshall, Patricia A.
TI "A rising tide lifts all boats": establishing a multidisciplinary
genomic tumor board for breast cancer patients with advanced disease
SO BMC MEDICAL GENOMICS
LA English
DT Article
DE Breast cancer; Genomics; Qualitative research; Patient care; Ethics
ID UNIVERSITY-OF-CALIFORNIA; PERSONALIZED MEDICINE; ONCOLOGY; CARE;
EXPERIENCE
AB Background: Research suggests that multidisciplinary genomic tumor boards (MGTB) can inform cancer patient care, though little is known about factors influencing how MGTBs interpret genomic test results, make recommendations, and perceive the utility of this approach. This study's objective was to observe, describe, and assess the establishment of the Breast Multidisciplinary Genomic Tumor Board, the first MGTB focused on interpreting genomic test results for breast cancer patients with advanced disease.
Methods: We conducted a qualitative case study involving participant observation at monthly MGTB meetings from October 2013 through November 2014 and interviews with 12 MGTB members. We analyzed social dynamics and interactions within the MGTB regarding interpretation of genomic findings and participants' views on effectiveness of the MGTB in using genomics to inform patient care.
Results: Twenty-two physicians, physician-scientists, basic scientists, bioethicists, and allied care professionals comprised the MGTB. The MGTB reviewed FoundationOne (TM) results for 40 metastatic breast cancer patients. Based on findings, the board mostly recommended referring patients to clinical trials (34) and medical genetics (15), and Food and Drug Administration-approved (FDA) breast cancer therapies (13). Though multidisciplinary, recommendations were driven by medical oncologists. Interviewees described providing more precise care recommendations and professional development as advantages and the limited actionability of genomic test results as a challenge for the MGTB.
Conclusions: Findings suggest both feasibility and desirability of pooling professional expertise in genomically-guided breast cancer care and challenges to institutionalizing a Breast MGTB, specifically in promoting interdisciplinary contributions and managing limited actionability of genomic test results for patients with advanced disease.
C1 [McGowan, Michelle L.] Univ Cincinnati, Dept Pediat & Womens Gender, Cincinnati Childrens Hosp Med Ctr, Eth Ctr,Div Gen & Community Pediat, 3333 Burnet Ave,MLC 15006, Cincinnati, OH 45229 USA.
[McGowan, Michelle L.] Univ Cincinnati, Dept Sexual Studies, Cincinnati Childrens Hosp Med Ctr, Eth Ctr,Div Gen & Community Pediat, 3333 Burnet Ave,MLC 15006, Cincinnati, OH 45229 USA.
[Ponsaran, Roselle S.] Case Western Reserve Univ, Sch Med, Cleveland, OH USA.
[Silverman, Paula] Case Western Reserve Univ, Sch Med, Univ Hosp, Seidman Canc Ctr, Cleveland, OH USA.
[Harris, Lyndsay N.] NCI, Washington, DC USA.
RP McGowan, ML (reprint author), Univ Cincinnati, Dept Pediat & Womens Gender, Cincinnati Childrens Hosp Med Ctr, Eth Ctr,Div Gen & Community Pediat, 3333 Burnet Ave,MLC 15006, Cincinnati, OH 45229 USA.; McGowan, ML (reprint author), Univ Cincinnati, Dept Sexual Studies, Cincinnati Childrens Hosp Med Ctr, Eth Ctr,Div Gen & Community Pediat, 3333 Burnet Ave,MLC 15006, Cincinnati, OH 45229 USA.
EM michelle.mcgowan@cchmc.org
FU National Human Genome Research Institute [P50HG003390]
FX Support for this research was provided by National Human Genome Research
Institute grant P50HG003390. The funding body was not involved in the
design of the study, the collection, analysis and interpretation of
data, nor the writing of the manuscript.
NR 35
TC 0
Z9 0
U1 2
U2 2
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1755-8794
J9 BMC MED GENOMICS
JI BMC Med. Genomics
PD NOV 21
PY 2016
VL 9
AR 71
DI 10.1186/s12920-016-0234-1
PG 10
WC Genetics & Heredity
SC Genetics & Heredity
GA EC7SI
UT WOS:000388340200001
PM 27871291
ER
PT J
AU Christensen, CH
Barry, KH
Andreotti, G
Alavanja, MCR
Cook, MB
Kelly, SP
Burdett, LA
Yeager, M
Freeman, LEB
Berndt, SI
Koutros, S
AF Christensen, Carol H.
Barry, Kathryn Hughes
Andreotti, Gabriella
Alavanja, Michael C. R.
Cook, Michael B.
Kelly, Scott P.
Burdett, Laurie A.
Yeager, Meredith
Freeman, Laura E. Beane
Berndt, Sonja I.
Koutros, Stella
TI Sex Steroid Hormone Single-Nucleotide Polymorphisms, Pesticide Use, and
the Risk of Prostate Cancer: A Nested Case-Control Study within the
Agricultural Health Study
SO FRONTIERS IN ONCOLOGY
LA English
DT Article
DE prostate cancer; pesticides; sex steroid hormones; single-nucleotide
polymorphism; interaction
ID DEPLOYMENT-RELATED CHEMICALS; GENOME-WIDE ASSOCIATION; REPAIR PATHWAY
GENES; METABOLIC PATHWAY; ANDROGEN RECEPTOR; 3A4 METABOLISM; EXPOSURE;
APPLICATORS; VARIANTS; COHORT
AB Experimental and epidemiologic investigations suggest that certain pesticides may alter sex steroid hormone synthesis, metabolism or regulation, and the risk of hormone-related cancers. Here, we evaluated whether single-nucleotide polymorphisms (SNPs) involved in hormone homeostasis alter the effect of pesticide exposure on prostate cancer risk. We evaluated pesticide-SNP interactions between 39 pesticides and SNPs with respect to prostate cancer among 776 cases and 1,444 controls nested in the Agricultural Health Study cohort. In these interactions, we included candidate SNPs involved in hormone synthesis, metabolism or regulation (N = 1,100), as well as SNPs associated with circulating sex steroid concentrations, as identified by genome-wide association studies (N = 17). Unconditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Multiplicative SNP-pesticide interactions were calculated using a likelihood ratio test. We translated p-values for interaction into q-values, which reflected the false discovery rate, to account for multiple comparisons. We observed a significant interaction, which was robust to multiple comparison testing, between the herbicide dicamba and rs8192166 in the testosterone metabolizing gene SRD5A1 (p-interaction = 4.0 x 10(-5); q-value = 0.03), such that men with two copies of the wild-type genotype CC had a reduced risk of prostate cancer associated with low use of dicamba (OR = 0.62 95% CI: 0.41, 0.93) and high use of dicamba (OR = 0.44, 95% CI: 0.29, 0.68), compared to those who reported no use of dicamba; in contrast, there was no significant association between dicamba and prostate cancer among those carrying one or two copies of the variant T allele at rs8192166. In addition, interactions between two organophosphate insecticides and SNPs related to estradiol metabolism were observed to result in an increased risk of prostate cancer. While replication is needed, these data suggest both agonistic and antagonistic effects on circulating hormones, due to the combination of exposure to pesticides and genetic susceptibility, may impact prostate cancer risk.
C1 [Christensen, Carol H.] US FDA, Off Sci, Ctr Tobacco Prod, Document Control Ctr, Silver Spring, MD USA.
[Barry, Kathryn Hughes; Andreotti, Gabriella; Alavanja, Michael C. R.; Freeman, Laura E. Beane; Berndt, Sonja I.; Koutros, Stella] NCI, Occupat & Environm Epidemiol Branch, US Dept HHS, Div Canc Epidemiol & Genet,NIH, Rockville, MD 20850 USA.
[Barry, Kathryn Hughes] Univ Maryland, Sch Med, Dept Epidemiol & Publ Hlth, Baltimore, MD 21201 USA.
[Barry, Kathryn Hughes] Univ Maryland, Program Oncol, Marlene & Stewart Greenebaum Comprehens Canc Ctr, Baltimore, MD 21201 USA.
[Cook, Michael B.; Kelly, Scott P.] NCI, Metab Epidemiol Branch, US Dept HHS, Div Canc Epidemiol & Genet,NIH, Rockville, MD USA.
[Burdett, Laurie A.; Yeager, Meredith] NCI, Canc Genom Res Lab, Frederick Natl Lab Canc Res, Leidos Biomed Res Inc, Frederick, MD 21701 USA.
RP Koutros, S (reprint author), NCI, Occupat & Environm Epidemiol Branch, US Dept HHS, Div Canc Epidemiol & Genet,NIH, Rockville, MD 20850 USA.
EM koutross@mail.nih.gov
RI Beane Freeman, Laura/C-4468-2015; Kelly, Scott/D-3195-2013
OI Beane Freeman, Laura/0000-0003-1294-4124; Kelly,
Scott/0000-0002-0375-1040
NR 50
TC 0
Z9 0
U1 5
U2 5
PU FRONTIERS MEDIA SA
PI LAUSANNE
PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015,
SWITZERLAND
SN 2234-943X
J9 FRONT ONCOL
JI Front. Oncol.
PD NOV 21
PY 2016
VL 6
AR 237
DI 10.3389/fonc.2016.00237
PG 8
WC Oncology
SC Oncology
GA EC6DN
UT WOS:000388226800001
PM 27917368
ER
PT J
AU Acevedo-Luna, N
Marino-Ramirez, L
Halbert, A
Hansen, U
Landsman, D
Spouge, JL
AF Acevedo-Luna, Natalia
Marino-Ramirez, Leonardo
Halbert, Armand
Hansen, Ulla
Landsman, David
Spouge, John L.
TI Most of the tight positional conservation of transcription factor
binding sites near the transcription start site reflects their
co-localization within regulatory modules
SO BMC BIOINFORMATICS
LA English
DT Article
DE Transcription factor binding site; Positional preference; Transcription
start site
ID OPEN-ACCESS DATABASE; LARGE GENE LISTS; STATISTICAL SIGNIFICANCE;
NUCLEOTIDE-SEQUENCES; FUNCTIONAL-ANALYSIS; HUMAN PROMOTERS; TARGET
GENES; MOTIF SITES; GENOME; EXPRESSION
AB Background: Transcription factors (TFs) form complexes that bind regulatory modules (RMs) within DNA, to control specific sets of genes. Some transcription factor binding sites (TFBSs) near the transcription start site (TSS) display tight positional preferences relative to the TSS. Furthermore, near the TSS, RMs can co-localize TFBSs with each other and the TSS. The proportion of TFBS positional preferences due to TFBS co-localization within RMs is unknown, however. ChIP experiments confirm co-localization of some TFBSs genome-wide, including near the TSS, but they typically examine only a few TFs at a time, using non-physiological conditions that can vary from lab to lab. In contrast, sequence analysis can examine many TFs uniformly and methodically, broadly surveying the colocalization of TFBSs with tight positional preferences relative to the TSS.
Results: Our statistics found 43 significant sets of human motifs in the JASPAR TF Database with positional preferences relative to the TSS, with 38 preferences tight (+/- 5 bp). Each set of motifs corresponded to a gene group of 135 to 3304 genes, with 42/43 (98%) gene groups independently validated by DAVID, a gene ontology database, with FDR < 0.05. Motifs corresponding to two TFBSs in a RM should co-occur more than by chance alone, enriching the intersection of the gene groups corresponding to the two TFs. Thus, a gene-group intersection systematically enriched beyond chance alone provides evidence that the two TFs participate in an RM. Of the 903 = 43*42/2 intersections of the 43 significant gene groups, we found 768/903 (85%) pairs of gene groups with significantly enriched intersections, with 564/768 (73%) intersections independently validated by DAVID with FDR < 0.05. A userfriendly web site at http://go.usa.gov/3kjsH permits biologists to explore the interaction network of our TFBSs to identify candidate subunit RMs.
Conclusions: Gene duplication and convergent evolution within a genome provide obvious biological mechanisms for replicating an RM near the TSS that binds a particular TF subunit. Of all intersections of our 43 significant gene groups, 85% were significantly enriched, with 73% of the significant enrichments independently validated by gene ontology. The co-localization of TFBSs within RMs therefore likely explains much of the tight TFBS positional preferences near the TSS.
C1 [Acevedo-Luna, Natalia] Iowa State Univ, Dept Genet Dev & Cell Biol, Ames, IA 50011 USA.
[Marino-Ramirez, Leonardo; Halbert, Armand; Landsman, David; Spouge, John L.] Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA.
[Hansen, Ulla] Boston Univ, Dept Biol, 5 Cummington Mall, Boston, MA 02215 USA.
RP Spouge, JL (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA.
EM spouge@nih.gov
FU Intramural Research Program of the National Institutes of Health;
National Library of Medicine; National Center for Biotechnology
Information; National Institutes of Health
FX This research was supported by the Intramural Research Program of the
National Institutes of Health, National Library of Medicine, and
National Center for Biotechnology Information. The National Institutes
of Health funded open access charges. The study was performed in part
when NAL was at the National Center for Biotechnology Information, NLM,
NIH, Bethesda.
NR 83
TC 0
Z9 0
U1 5
U2 5
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2105
J9 BMC BIOINFORMATICS
JI BMC Bioinformatics
PD NOV 21
PY 2016
VL 17
AR 479
DI 10.1186/s12859-016-1354-5
PG 12
WC Biochemical Research Methods; Biotechnology & Applied Microbiology;
Mathematical & Computational Biology
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Mathematical & Computational Biology
GA EC4RA
UT WOS:000388119900001
PM 27871221
ER
PT J
AU Brickley, EB
Coulibaly, M
Gabriel, EE
Healy, SA
Hume, JCC
Sagara, I
Traore, SF
Doumbo, O
Duffy, PE
AF Brickley, Elizabeth B.
Coulibaly, Mamadou
Gabriel, Erin E.
Healy, Sara A.
Hume, Jen C. C.
Sagara, Issaka
Traore, Sekou F.
Doumbo, Ogobara
Duffy, Patrick E.
TI Utilizing direct skin feeding assays for development of vaccines that
interrupt malaria transmission: A systematic review of methods and case
study
SO VACCINE
LA English
DT Review
DE Transmission-blocking vaccine; Malaria; Trial design; Direct skin feed;
Vaccine activity
ID PLASMODIUM-FALCIPARUM; ANOPHELES-GAMBIAE; BLOCKING VACCINE; GAMETOCYTE
CARRIERS; WESTERN KENYA; MOSQUITOS; INFECTIVITY; AREA; INFECTIOUSNESS;
POPULATION
AB Shifting the malaria priorities from a paradigm of control and elimination to a goal of global eradication calls for renewed attention to the interruption of malaria transmission. Sustained progress toward eradication will require both improved understanding of infectious reservoirs and efficient development of novel transmission-blocking interventions, such as rapidly acting and highly efficacious therapeutics and vaccines. Here, we review the direct skin feeding assay (DSF), which has been proposed as a valuable tool for measuring the in ttatura transmission of malaria parasites from human hosts to mosquito vectors across heterogeneous populations. To capture the methodological breadth of this assay's use, we first systematically review and qualitatively synthesize previously published investigations using DSFs to study malaria transmission in humans. Then, using a recent Phase 1 trial in Mali of the Pfs25H-EPA/Alhydrogel (R) vaccine candidate (NCT01867463) designed to interrupt Plasmodium falciparum transmission as a case study, we describe the potential opportunities and current limitations of utilizing the endpoints measured by DSF in making early clinical decisions for individually randomized transmission-interrupting intervention candidates. Using simulations based on the data collected in the clinical trial, we demonstrate that the capacity of the DSF to serve as an evaluative tool is limited by the statistical power constraints of the "effective sample size" (i.e. the number of subjects that are capable of transmitting at the time of feeding). Altogether, our findings suggest DSFs have great potential utility for assessing the public health impacts of emerging antimalarial tools, but additional research is needed to address issues of scalability and to establish correlation with community-wide clinical endpoints as well as complementary in vitro measures, such as standard membrane feeding assays. Published by Elsevier Ltd.
C1 [Brickley, Elizabeth B.; Healy, Sara A.; Hume, Jen C. C.; Duffy, Patrick E.] NIAID, Lab Malaria Immunol & Vaccinol, NIH, Twinbrook 1,Room 1111,5640 Fishers Lane, Rockville, MD 20852 USA.
[Brickley, Elizabeth B.] Univ Cambridge, Dept Publ Hlth & Primary Care, Strangeways Res Lab, Worts Causeway, Cambridge CB1 8RN, Cambs, England.
[Brickley, Elizabeth B.] Geisel Sch Med Dartmouth, Dept Epidemiol, 1 Med Ctr Dr,7927 Rubin Bldg, Lebanon, NH 03756 USA.
[Coulibaly, Mamadou; Sagara, Issaka; Traore, Sekou F.; Doumbo, Ogobara] Univ Sci Tech & Technol Bamako, Fac Pharm, Dept Epidemiol Parasit Dis, Malaria Res & Training Ctr, POB 1805, Bamako, Mali.
[Coulibaly, Mamadou; Sagara, Issaka; Traore, Sekou F.; Doumbo, Ogobara] Univ Sci Tech & Technol Bamako, Fac Med & Dent, POB 1805, Bamako, Mali.
[Gabriel, Erin E.] NIAID, Biostat Res Branch, NIH, 5601 Fishers Lane, Rockville, MD 20852 USA.
RP Duffy, PE (reprint author), NIAID, Lab Malaria Immunol & Vaccinol, NIH, Twinbrook 1,Room 1111,5640 Fishers Lane, Rockville, MD 20852 USA.
EM elizabeth.b.brickley@dartmouth.edu; doudou@icermali.org;
erin.gabriel@nih.gov; sara.healy@nih.gov; jennifer.hume@nih.gov;
isagara@icermali.org; cheick@icermali.org; okd@icermali.org;
patrick.duffy@nih.gov
OI Gabriel, Erin/0000-0002-0504-8404; Coulibaly, Mamadou
Brahima/0000-0001-9325-2845
FU Intramural Research Program of the National Institute of Allergy and
Infectious Diseases, National Institutes of Health; National Institutes
of Health Oxford Cambridge Scholars Program; National Cancer Institute
of the National Institutes of Health [R25CA134286]
FX This work was supported by the Intramural Research Program of the
National Institute of Allergy and Infectious Diseases, National
Institutes of Health [http://www.niaid.nih.gov/]. During the duration of
study, EBB was supported by the National Institutes of Health Oxford
Cambridge Scholars Program [http://oxcam.gpp.nih.gov/] and by the
National Cancer Institute of the National Institutes of Health under
Award Number R25CA134286.
NR 33
TC 0
Z9 0
U1 4
U2 4
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0264-410X
EI 1873-2518
J9 VACCINE
JI Vaccine
PD NOV 21
PY 2016
VL 34
IS 48
BP 5863
EP 5870
DI 10.1016/j.vaccine.2016.10.027
PG 8
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA EC3XG
UT WOS:000388059800008
PM 27789147
ER
PT J
AU Kim, Y
Bae, SK
Cheng, TM
Tao, C
Ge, YH
Chapman, AB
Torres, VE
Yu, ASL
Mrug, M
Bennett, WM
Flessner, MF
Landsittel, DP
Bae, KT
AF Kim, Youngwoo
Bae, Sonu K.
Cheng, Tianming
Tao, Cheng
Ge, Yinghui
Chapman, Arlene B.
Torres, Vincente E.
Yu, Alan S. L.
Mrug, Michal
Bennett, William M.
Flessner, Michael F.
Landsittel, Doug P.
Bae, Kyongtae T.
TI Automated segmentation of liver and liver cysts from bounded abdominal
MR images in patients with autosomal dominant polycystic kidney disease
SO PHYSICS IN MEDICINE AND BIOLOGY
LA English
DT Article
DE autosomal dominant kidney disease; polycystic liver disease; image
segmentation; prior probability map; level set
ID STATISTICAL SHAPE MODEL; PROBABILISTIC ATLAS; HEPATIC CYSTS; CT IMAGES;
CONSTRUCTION; INVOLVEMENT; PROGRESSION; ALGORITHMS; CONSORTIUM;
VOLUMETRY
AB Liver and liver cyst volume measurements are important quantitative imaging biomarkers for assessment of disease progression in autosomal dominant polycystic kidney disease (ADPKD) and polycystic liver disease (PLD). To date, no study has presented automated segmentation and volumetric computation of liver and liver cysts in these populations. In this paper, we proposed an automated segmentation framework for liver and liver cysts from bounded abdominal MR images in patients with ADPKD. To model the shape and variations in ADPKD livers, the spatial prior probability map (SPPM) of liver location and the tissue prior probability maps (TPPMs) of liver parenchymal tissue intensity and cyst morphology were generated. Formulated within a three-dimensional level set framework, the TPPMs successfully captured liver parenchymal tissues and cysts, while the SPPM globally constrained the initial surfaces of the liver into the desired boundary. Liver cysts were extracted by combined operations of the TPPMs, thresholding, and false positive reduction based on spatial prior knowledge of kidney cysts and distance map. With cross-validation for the liver segmentation, the agreement between the radiology expert and the proposed method was 84% for shape congruence and 91% for volume measurement assessed by the intra-class correlation coefficient (ICC). For the liver cyst segmentation, the agreement between the reference method and the proposed method was ICC = 0.91 for cyst volumes and ICC = 0.94 for % cyst-to-liver volume.
C1 [Kim, Youngwoo; Bae, Sonu K.; Cheng, Tianming; Tao, Cheng; Ge, Yinghui; Bae, Kyongtae T.] Univ Pittsburgh, Sch Med, Dept Radiol, 3362 Fifth Ave, Pittsburgh, PA 15213 USA.
[Chapman, Arlene B.] Emory Univ, Sch Med, Dept Internal Med, Atlanta, GA 30307 USA.
[Torres, Vincente E.] Mayo Coll Med, Dept Internal Med, Rochester, MN 55905 USA.
[Yu, Alan S. L.] Univ Kansas, Med Ctr, Dept Internal Med, Kansas City, KS 66160 USA.
[Mrug, Michal] Univ Alabama Birmingham, Div Nephrol, Birmingham, AL 35487 USA.
[Bennett, William M.] Legacy Good Samaritan Hosp, Portland, OR 97210 USA.
[Flessner, Michael F.] NIDDK, NIH, Bethesda, MD 20892 USA.
[Landsittel, Doug P.] Univ Pittsburgh, Sch Med, Dept Internal Med, Pittsburgh, PA 15213 USA.
RP Bae, KT (reprint author), Univ Pittsburgh, Sch Med, Dept Radiol, 3362 Fifth Ave, Pittsburgh, PA 15213 USA.
EM baek@upmc.edu
FU National Institute of Diabetes and Digestive; Kidney Diseases of the
National Institutes of Health [DK056943, DK056956, DK056957, DK056961];
National Center for Research Resources General Clinical Research Centers
at Emory University [RR000039]; National Center for Research Resources
General Clinical Research Centers at Mayo College of Medicine [RR00585];
National Center for Research Resources General Clinical Research Centers
at Kansas University Medical Center [RR23940]; National Center for
Research Resources General Clinical Research Centers at University of
Alabama at Birmingham [RR000032]; National Center for Research Resources
Clinical and Translational Science Awards at Emory [RR025008]; National
Center for Research Resources Clinical and Translational Science Awards
at Mayo College of Medicine [RR024150]; National Center for Research
Resources Clinical and Translational Science Awards at Kansas University
Medical Center [RR033179]; National Center for Research Resources
Clinical and Translational Science Awards at University of Alabama at
Birmingham [RR025777, UL1TR000165]; National Center for Research
Resources Clinical and Translational Science Awards at University of
Pittsburgh School of Medicine [RR024153, UL1TR000005]
FX The CRISP study is supported by cooperative agreements from the National
Institute of Diabetes and Digestive and Kidney Diseases of the National
Institutes of Health (DK056943, DK056956, DK056957, DK056961), by the
National Center for Research Resources General Clinical Research Centers
at each institution (RR000039, Emory University; RR00585, Mayo College
of Medicine; RR23940, Kansas University Medical Center; RR000032,
University of Alabama at Birmingham), and the National Center for
Research Resources Clinical and Translational Science Awards at each
institution (RR025008, Emory; RR024150, Mayo College of Medicine;
RR033179, Kansas University Medical Center; RR025777 and UL1TR000165,
University of Alabama at Birmingham; RR024153 and UL1TR000005,
University of Pittsburgh School of Medicine). The investigators are
indebted to the radiologists, nephrologists, radiology technologists,
imaging engineers, and study coordinators in CRISP.
NR 42
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U1 1
U2 1
PU IOP PUBLISHING LTD
PI BRISTOL
PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND
SN 0031-9155
EI 1361-6560
J9 PHYS MED BIOL
JI Phys. Med. Biol.
PD NOV 21
PY 2016
VL 61
IS 22
BP 7864
EP 7880
DI 10.1088/0031-9155/61/22/7864
PG 17
WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging
SC Engineering; Radiology, Nuclear Medicine & Medical Imaging
GA EB1VM
UT WOS:000387143900003
ER
PT J
AU Zhang, D
Wlodawer, A
Lubkowski, J
AF Zhang, Di
Wlodawer, Alexander
Lubkowski, Jacek
TI Crystal Structure of a Complex of the Intracellular Domain of Interferon
lambda Receptor 1 (IFNLR1) and the FERM/SH2 Domains of Human JAK1
SO JOURNAL OF MOLECULAR BIOLOGY
LA English
DT Article
DE JAK/STAT signaling; cytokine receptors; Janus kinases; protein-protein
interactions; structure comparisons
ID SIGNAL TRANSDUCER GP130; JANUS KINASES; MOLECULAR REPLACEMENT; CYTOKINE
RECEPTORS; PROTEIN-KINASE; SH2 DOMAIN; RECOGNITION; ACTIVATION;
EXPRESSION; FAMILY
AB The crystal structure of a construct consisting of the FERM and SH2-like domains of the human Janus kinase 1 (JAK1) bound to a fragment of the intracellular domain of the interferon-lambda receptor 1 (IFNLR1) has. been determined at the nominal resolution of 2.1 A. In this structure, the receptor peptide forms an 85-angstrom-long extended chain, in which both the previously identified box1 and box2 regions bind simultaneously to the FERM and SH2-like domains of JAK1. Both domains of JAK1 are generally well ordered, with regions not seen in the crystal structure limited to loops located away from the receptor-binding regions. The structure provides a much more complete and accurate picture of the interactions between JAK1 and IFNLR1 than those given in earlier reports, illuminating the molecular basis of the JAK cytokine receptor association. A glutamate residue adjacent to the box2 region in IFNLR1 mimics the mode of binding of a phosphotyrosine in classical SH2 domains. It was shown here that a deletion of residues within the box1 region of the receptor abolishes stable interactions with JAK1, although it was previously shown that box2 alone is sufficient to stabilize a similar complex of the interferon-alpha receptor and TYK2. Published by Elsevier Ltd.
C1 [Zhang, Di; Wlodawer, Alexander; Lubkowski, Jacek] NCI, Macromol Crystallog Lab, Ctr Canc Res, Frederick, MD 21702 USA.
RP Wlodawer, A; Lubkowski, J (reprint author), NCI, Macromol Crystallog Lab, Ctr Canc Res, Frederick, MD 21702 USA.
EM wlodawer@nih.gov; lubkowsj@mail.nih.gov
FU National Institutes of Health (NIH), National Cancer Institute, Center
for Cancer Research; U.S. Department of Energy, Office of Science,
Office of Basic Energy Sciences [W-31-109-Eng-38]
FX This project was supported by the Intramural Research Program of the
National Institutes of Health (NIH), National Cancer Institute, Center
for Cancer Research. Data were collected at Southeast Regional
Collaborative Access Team (SER-CAT) 22-ID beamline at the Advanced
Photon Source, Argonne National Laboratory. Supporting institutions may
be found at www.ser-cat.org/members.html. Use of the APS 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.
NR 44
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U1 4
U2 4
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0022-2836
EI 1089-8638
J9 J MOL BIOL
JI J. Mol. Biol.
PD NOV 20
PY 2016
VL 428
IS 23
BP 4651
EP 4668
DI 10.1016/j.jmb.2016.10.005
PG 18
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA ED8GP
UT WOS:000389110300006
PM 27725180
ER
PT J
AU Mehalko, JL
Esposito, D
AF Mehalko, Jennifer L.
Esposito, Dominic
TI Engineering the transposition-based baculovirus expression vector system
for higher efficiency protein production from insect cells
SO JOURNAL OF BIOTECHNOLOGY
LA English
DT Article
DE Baculovirus; Insect cells; Tn7 transposition; Bac-to-Bac; Protein
production
ID ESCHERICHIA-COLI; RECOMBINANT BACULOVIRUSES; DNA-REPLICATION; TN7;
GENERATION; INSERTION; SEQUENCE; ORIGIN; GENES
AB One of the most common methods for producing recombinant baculovirus for insect cell protein production involves a transposition mediated system invented over 2 decades ago. This Tn7-mediated system, commercially sold as Bac-to-Bac, has proven highly useful for construction of high quality baculovirus, but suffers from a number of drawbacks which reduce the efficiency of the process and limit its utility for high throughput protein production processes. We describe here the creation of Bac-2-the-Future, a 2nd generation Tn7-based system for recombinant baculovirus production which uses optimized expression vectors, new E. coli strains, and enhanced protocols to dramatically enhance the efficiency of the baculovirus production process. The new system which we describe eliminates the need for additional screening of positive clones, improves the efficiency of transposition, and reduces the cost and time required for high throughput baculovirus production. The system is compatible with multiple cloning methodologies, and has been demonstrated to produce baculovirus with equal or better titer and protein productivity than the currently available systems. (C) 2016 Elsevier B.V. All rights reserved.
C1 [Mehalko, Jennifer L.; Esposito, Dominic] Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Canc Res Technol Program, Prot Express Lab, POB B, Frederick, MD 21702 USA.
RP Esposito, D (reprint author), Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Canc Res Technol Program, Prot Express Lab, POB B, Frederick, MD 21702 USA.
EM dom.esposito@nih.gov
FU National Cancer Institute, National Institutes of Health
[HHSN261200800001E]
FX We acknowledge the technical support of Ralph Hopkins, Cammi Bittner,
and Matt Drew for baculovirus production and insect cell expression
culture work. 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. Vectors and strains described in this manuscript are
freely available to academic and non-profit researchers by contacting
the authors, and some B2F vectors will shortly be available at Addgene
(http://www.acidgene.org). For-profit companies that are interested in
obtaining B2F materials should contact the National Cancer Institute
Office of Technology Transfer.
NR 22
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U1 13
U2 13
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0168-1656
EI 1873-4863
J9 J BIOTECHNOL
JI J. Biotechnol.
PD NOV 20
PY 2016
VL 238
BP 1
EP 8
DI 10.1016/j.jbiotec.2016.002
PG 8
WC Biotechnology & Applied Microbiology
SC Biotechnology & Applied Microbiology
GA DZ0II
UT WOS:000385521100001
PM 27616621
ER
PT J
AU Kunimatsu, J
Tanaka, M
AF Kunimatsu, Jun
Tanaka, Masaki
TI STRIATAL DOPAMINE MODULATES TIMING OF SELF-INITIATED SACCADES
SO NEUROSCIENCE
LA English
DT Article
DE self-timing; saccade; dopamine; acetylcholine; basal ganglia; primate
ID PRIMATE MOTOR THALAMUS; BASAL GANGLIA; PARKINSONS-DISEASE;
NUCLEUS-ACCUMBENS; SUPERIOR COLLICULUS; PROJECTION NEURONS;
NONHUMAN-PRIMATES; PREFRONTAL CORTEX; COGNITIVE SIGNALS;
SUBSTANTIA-NIGRA
AB The ability to adjust movement timing is essential in daily life. Explorations of the underlying neural mechanisms have reported a gradual increase or decrease in neuronal activity prior to self-timed movements within the cortico-basal ganglia loop. Previous studies in both humans and animals have shown that endogenous dopamine (DA) plays a modulatory role in self-timing. However, the specific site of dopaminergic regulation remains elusive because the systemic application of DA-related substances can directly alter both cortical and subcortical neuronal activities. To investigate the role of striatal DA in self-timing, we locally injected DA receptor agonists or antagonists into the striatum of two female monkeys (Macaca fuscata) while they performed two versions of the memory-guided saccade (MS) task. In the conventional, triggered MS task, animals made a saccade to the location of a previously flashed visual cue in response to the fixation point offset. In the self-timed MS task, monkeys were rewarded for making a self-initiated saccade within a predetermined time interval following the cue. Infusion of a small amount of a D-1 or D-2 antagonist led to early saccades in the self-timed, but not the triggered MS tasks, while infusion of DA agonists produced no consistent effect. We also found that local administration of nicotinic but not muscarinic acetylcholine receptor agonists and antagonists altered the timing of self-initiated saccades. Our data suggest that the timing of self-initiated movements may be regulated by the balance of signals in the direct and indirect basal ganglia pathways, as well as that between both hemispheres of the brain. Published by Elsevier Ltd on behalf of IBRO.
C1 [Kunimatsu, Jun; Tanaka, Masaki] Hokkaido Univ, Dept Physiol, Sch Med, North 15,West 7, Sapporo, Hokkaido 0608638, Japan.
[Kunimatsu, Jun] NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA.
RP Kunimatsu, J; Tanaka, M (reprint author), Hokkaido Univ, Dept Physiol, Sch Med, North 15,West 7, Sapporo, Hokkaido 0608638, Japan.
EM kunimatsu.jun@gmail.com; masa-ki@med.hokudai.ac.jp
RI Tanaka, Masaki/D-9199-2011
FU Japan Science and Technology Agency; Ministry of Education, Culture,
Sports, Science and Technology of Japan; Ministry of Health, Labour and
Welfare of Japan; Smoking Research Foundation; Takeda Science Foundation
FX The authors thank S. Ohmae, T. Suzuki, and other lab members for
valuable comments and discussions; T. Mori and A. Hironaka for their
assistance with animal care, training and MRI scanning; and M. Suzuki
for her administrative help. We are grateful to M. Takei and Y. Hirata
in the Equipment Development Group, Research Institute for Electronic
Science, Hokkaido University, for manufacturing some equipment. This
work was supported in part by grants from the Japan Science and
Technology Agency, the Ministry of Education, Culture, Sports, Science
and Technology of Japan, the Ministry of Health, Labour and Welfare of
Japan, the Smoking Research Foundation, and the Takeda Science
Foundation.
NR 80
TC 0
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U1 4
U2 4
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0306-4522
EI 1873-7544
J9 NEUROSCIENCE
JI Neuroscience
PD NOV 19
PY 2016
VL 337
BP 131
EP 142
DI 10.1016/j.neuroscience.2016.09.006
PG 12
WC Neurosciences
SC Neurosciences & Neurology
GA EA1FJ
UT WOS:000386337600012
PM 27651148
ER
PT J
AU Medhi, D
Goldman, ASH
Lichten, M
AF Medhi, Darpan
Goldman, Alastair S. H.
Lichten, Michael
TI Local chromosome context is a major determinant of crossover pathway
biochemistry during budding yeast meiosis
SO ELIFE
LA English
DT Article
ID DOUBLE-STRAND BREAKS; MEIOTIC GENE CONVERSION; SYNAPTONEMAL
COMPLEX-FORMATION; DOUBLE HOLLIDAY JUNCTIONS; SACCHAROMYCES-CEREVISIAE;
RECOMBINATION HOTSPOTS; SISTER CHROMATIDS; CHECKPOINT KINASE;
HETERODUPLEX DNA; DISTINCT ROLES
AB The budding yeast genome contains regions where meiotic recombination initiates more frequently than in others. This pattern parallels enrichment for the meiotic chromosome axis proteins Hop1 and Red1. These proteins are important for Spo11-catalyzed double strand break formation; their contribution to crossover recombination remains undefined. Using the sequence-specific VMA1-derived endonuclease (VDE) to initiate recombination in meiosis, we show that chromosome structure influences the choice of proteins that resolve recombination intermediates to form crossovers. At a Hop1-enriched locus, most VDE-initiated crossovers, like most Spo11-initiated crossovers, required the meiosis-specific MutL gamma resolvase. In contrast, at a locus with lower Hop1 occupancy, most VDE-initiated crossovers were MutL gamma-independent. In pch2 mutants, the two loci displayed similar Hop1 occupancy levels, and VDE-induced crossovers were similarly MutL gamma-dependent. We suggest that meiotic and mitotic recombination pathways coexist within meiotic cells, and that features of meiotic chromosome structure determine whether one or the other predominates in different regions.
C1 [Medhi, Darpan; Lichten, Michael] NCI, Lab Biochem & Mol Biol, Ctr Canc Res, Bethesda, MD 20892 USA.
[Medhi, Darpan; Goldman, Alastair S. H.] Univ Sheffield, Sheffield Inst Nucle Acids, Sheffield, S Yorkshire, England.
[Medhi, Darpan; Goldman, Alastair S. H.] Univ Sheffield, Dept Mol Biol & Biotechnol, Sheffield, S Yorkshire, England.
RP Lichten, M (reprint author), NCI, Lab Biochem & Mol Biol, Ctr Canc Res, Bethesda, MD 20892 USA.
EM mlichten@helix.nih.gov
OI Lichten, Michael/0000-0001-9707-2956
FU National Cancer Institute Intramural Research Program of the NIH through
the Center for Cancer Research at the National Cancer Institute;
University of Sheffield
FX National Cancer Institute Intramural Research Program of the NIH through
the Center for Cancer Research at the National Cancer Institute Michael
Lichten; University of Sheffield Graduate tuition grant Darpan Medhi;
The funders had no role in study design, data collection and
interpretation, or the decision to submit the work for publication.
NR 110
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U1 5
U2 5
PU ELIFE SCIENCES PUBLICATIONS LTD
PI CAMBRIDGE
PA SHERATON HOUSE, CASTLE PARK, CAMBRIDGE, CB3 0AX, ENGLAND
SN 2050-084X
J9 ELIFE
JI eLife
PD NOV 18
PY 2016
VL 5
AR e19669
DI 10.7554/eLife.19669
PG 20
WC Biology
SC Life Sciences & Biomedicine - Other Topics
GA EJ7GT
UT WOS:000393390500001
ER
PT J
AU Chan, STS
Nani, RR
Schauer, EA
Martin, GE
Williamson, RT
Sauri, J
Buevich, AV
Schafer, WA
Joyce, LA
Goey, AKL
Figg, WD
Ransom, TT
Henrich, CJ
Mckee, TC
Moser, A
MacDonald, SA
Khan, S
McMahon, JB
Schnermann, MJ
Gustafson, KR
AF Chan, Susanna T. S.
Nani, Roger R.
Schauer, Evan A.
Martin, Gary E.
Williamson, R. Thomas
Sauri, Josep
Buevich, Alexei V.
Schafer, Wes A.
Joyce, Leo A.
Goey, Andrew K. L.
Figg, William D.
Ransom, Tanya T.
Henrich, Curtis J.
Mckee, Tawnya C.
Moser, Arvin
MacDonald, Scott A.
Khan, Shabana
McMahon, James B.
Schnermann, Martin J.
Gustafson, Kirk R.
TI Characterization and Synthesis of Eudistidine C, a Bioactive Marine
Alkaloid with an Intriguing Molecular Scaffold
SO JOURNAL OF ORGANIC CHEMISTRY
LA English
DT Article
ID ASSISTED STRUCTURE ELUCIDATION; LR-HSQMBC; NMR; SOFTWARE
AB An extract of Eudistoma sp. provided eudistidine C (1), a heterocyclic alkaloid with a novel molecular framework. Eudistidine C (1) is a racemic natural product composed of a tetracyclic core structure further elaborated with a p-methoxyphenyl group and a phenol-substituted aminoimidazole moiety. This compound presented significant structure elucidation challenges due to the large number of heteroatoms and fully substituted carbons. These issues were mitigated by application of a new NMR pulse sequence (LR-EISQMBC) optimized to detect four- and five-bond heteronuclear correlations and the use of computer-assisted structure elucidation software. Synthesis of eudistidine C (1) was accomplished in high yield by treating eudistidine A (2) with 4(2-amino-1H-irnidazol-5-yl)phenol (4) in DMSO. Synthesis of eudistidine C (1) confirmed the proposed structure and provided material for further biological characterization. Treatment of 2 with various nitrogen heterocycles and electron-rich arenes provided a series of analogues (5-10) of eudistidine C. Chiral-phase HPLC resolution of epimeric eudistidine C provided (+)-(R)-eudistidine C (la) and (-)-(S)-eudistidine C (1b). The absolute configuration of these enantiomers was assigned by ECD analysis. (-)-(S)-Eudistidine C (lb) modestly inhibited interaction between the protein binding domains of HIF-1 alpha and p300. Compounds 1, 2, and 6-10 exhibited significant antimalarial activity against Plasmodium falciparum.
C1 [Chan, Susanna T. S.; Ransom, Tanya T.; Henrich, Curtis J.; Mckee, Tawnya C.; McMahon, James B.; Gustafson, Kirk R.] NCI, Mol Targets Lab, Ctr Canc Res, Frederick, MD 21702 USA.
[Nani, Roger R.; Schauer, Evan A.; Schnermann, Martin J.] NCI, Biol Chem Lab, Ctr Canc Res, Frederick, MD 21702 USA.
[Martin, Gary E.; Williamson, R. Thomas; Sauri, Josep; Buevich, Alexei V.; Schafer, Wes A.; Joyce, Leo A.] Merck & Co Inc, NMR Struct Elucidat Proc Res & Dev, Rahway, NJ 07065 USA.
[Goey, Andrew K. L.; Figg, William D.] NCI, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Henrich, Curtis J.] Leidos Biomed Res Inc, Basic Sci Program, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
[Moser, Arvin; MacDonald, Scott A.] Adv Chem Dev Inc, Toronto Dept, ACD Labs, 8 King St East Suite 107, Toronto, ON M5C 1B5, Canada.
[Khan, Shabana] Univ Mississippi, Sch Pharm, Natl Ctr Nat Prod Res, University, MS 38677 USA.
[Mckee, Tawnya C.] NCI, Diagnost Biomarkers & Technol Branch, Canc Diag Program, DCTD, Bethesda, MD 20850 USA.
[Schauer, Evan A.] Baylor Coll Med, 1 Baylor Plaza, Houston, TX 77030 USA.
RP Gustafson, KR (reprint author), NCI, Mol Targets Lab, Ctr Canc Res, Frederick, MD 21702 USA.; Schnermann, MJ (reprint author), NCI, Biol Chem Lab, Ctr Canc Res, Frederick, MD 21702 USA.
EM martin.schnermann@nih.gov; gustafki@mail.nih.gov
OI Sauri, Josep/0000-0002-2706-2426
FU Intramural Research Program of the NIH, National Cancer Institute,
Center for Cancer Research; Federal funds from National Cancer
Institute, National Institutes of Health [HHSN261200800001E]; USDA
Agricultural Research Service [58-6408-1-603]
FX We gratefully acknowledge D. Newman (NCI) for organizing and documenting
the collection, the Natural Products Support Group at NCI Frederick for
extraction, T. Bostaph (MTL) and K. Goncharova (MTL) for screening data
compilation and analysis, J. Barchi (CBL) for NMR assistance, J. Kelly
(CBL) for mass spectrometry analysis, and S. Tarasov and M. Dyba
(Biophysics Resource Core, Structural Biophysics Laboratory, CCR) and H.
Bokesch (MTL) for assistance with high resolution mass spectrometry.
This research was supported in part by the Intramural Research Program
of the NIH, National Cancer Institute, Center for Cancer Research. This
project was also funded in part with Federal funds from the National
Cancer Institute, National Institutes of Health, under contract
HHSN261200800001E and by the USDA Agricultural Research Service Specific
Cooperative Agreement No. 58-6408-1-603. The content of this publication
does not necessarily reflect the views or policies of the Department of
Health and Human Services, nor does mention of trade names, commercial
products, or organizations imply endorsement by the US Government.
NR 18
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U1 4
U2 4
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0022-3263
J9 J ORG CHEM
JI J. Org. Chem.
PD NOV 18
PY 2016
VL 81
IS 22
BP 10631
EP 10640
DI 10.1021/acs.joc.6b02380
PG 10
WC Chemistry, Organic
SC Chemistry
GA EG7SI
UT WOS:000391248800004
PM 27934476
ER
PT J
AU Davis, MI
Pragani, R
Fox, JT
Shen, M
Parmar, K
Gaudiano, EF
Liu, L
Tanega, C
Mcgee, L
Hall, MD
McKnight, C
Shinn, P
Nelson, H
Chattopadhyay, D
D'Andrea, AD
Auld, DS
DeLucas, LJ
Li, ZY
Boxer, MB
Sinneonov, A
AF Davis, Mindy I.
Pragani, Rajan
Fox, Jennifer T.
Shen, Min
Parmar, Kalindi
Gaudiano, Emily F.
Liu, Li
Tanega, Cordelle
McGee, Lauren
Hall, Matthew D.
McKnight, Crystal
Shinn, Paul
Nelson, Henrike
Chattopadhyay, Debasish
D'Andrea, Alan D.
Auld, Douglas S.
DeLucas, Larry J.
Li, Zhuyin
Boxer, Matthew B.
Sinneonov, Anton
TI Small Molecule Inhibition of the Ubiquitin-specific Protease USP2
Accelerates cyclin D1 Degradation and Leads to Cell Cycle Arrest in
Colorectal Cancer and Mantle Cell Lymphoma Models
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID FATTY-ACID SYNTHASE; PROSTATE-CANCER; DNA-DAMAGE; MAMMALIAN-CELLS;
STABILITY; REPAIR; TARGET
AB Deubiquitinases are important components of the protein degradation regulatory network. We report the discovery of ML364, a small molecule inhibitor of the deubiquitinase USP2 and its use to interrogate the biology of USP2 and its putative substrate cyclin DL ML364 has an IC50 of 1.1 mu M in a biochemical assay using an internally quenched fluorescent di-ubiquitin substrate. Direct binding of ML364 to USP2 was demonstrated using microscale thermophoresis. ML364 induced an increase in cellular cyclin D1 degradation and caused cell cycle arrest as shown in Western blottings and flow cytometry assays utilizing both Mino and HCT116 cancer cell lines. ML364, and not the inactive analog 2, was antiproliferative in cancer cell lines. Consistent with the role of cyclin D1 in DNA damage response, ML364 also caused a decrease in homologous recombination mediated DNA repair. These effects by a small molecule inhibitor support a key role for USP2 as a regulator of cell cycle, DNA repair, and tumor cell growth.
C1 [Davis, Mindy I.; Pragani, Rajan; Fox, Jennifer T.; Shen, Min; Liu, Li; Tanega, Cordelle; McGee, Lauren; Hall, Matthew D.; McKnight, Crystal; Shinn, Paul; Nelson, Henrike; Auld, Douglas S.; Li, Zhuyin; Boxer, Matthew B.; Sinneonov, Anton] NIH, Chem Genom Ctr, Natl Ctr Adv Translat Sci, Bldg 10, Bethesda, MD 20892 USA.
[Parmar, Kalindi; Gaudiano, Emily F.; D'Andrea, Alan D.] Harvard Med Sch, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02215 USA.
[Chattopadhyay, Debasish; DeLucas, Larry J.] Univ Alabama Birmingham, Struct Biol Ctr, Birmingham, AL 35294 USA.
[Auld, Douglas S.] Novartis Inst Biomed Res, Ctr Proteorn Chem, Cambridge, MA 02139 USA.
RP Boxer, MB; Sinneonov, A (reprint author), NIH, NCATS, 9800 Med Ctr Dr, Rockville, MD 20850 USA.
EM boxerrn@mail.nih.gov; asimeono@mail.nih.gov
FU NCATS Intramural Research Program; Molecular Libraries Initiative of the
National Institutes of Health Common Fund; National Institutes of Health
[U54 MH 084681]; Alabama Drug Discovery Alliance; National Institutes of
Health/NCI Grant [5P30CA13148-37]; Translational Research Grant from the
Leukemia & Lymphoma Society [6237-13]
FX This work was supported by the NCATS Intramural Research Program,
Molecular Libraries Initiative of the National Institutes of Health
Common Fund, National Institutes of Health Grant U54 MH 084681, Alabama
Drug Discovery Alliance, National Institutes of Health/NCI Grant
5P30CA13148-37, and Translational Research Grant from the Leukemia &
Lymphoma Society Grant 6237-13. The authors declare that they have no
conflicts of interest with the contents of this article. The content is
solely the responsibility of the authors and does not necessarily
represent the official views of the National Institutes of Health.
NR 36
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U1 3
U2 3
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
EI 1083-351X
J9 J BIOL CHEM
JI J. Biol. Chem.
PD NOV 18
PY 2016
VL 291
IS 47
BP 24628
EP 24640
DI 10.1074/jbc.M116.738567
PG 13
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA ED5EX
UT WOS:000388875500024
PM 27681596
ER
PT J
AU de Vasconcellos, JF
Lee, YT
Byrnes, C
Tumburu, L
Rebel, A
Miller, JL
AF de Vasconcellos, Jaira F.
Lee, Y. Terry
Byrnes, Colleen
Tumburu, Laxminath
Rebel, Antoinette
Miller, Jeffery L.
TI HMGA2 Moderately Increases Fetal Hemoglobin Expression in Human Adult
Erythroblasts
SO PLOS ONE
LA English
DT Article
ID SICKLE-CELL-DISEASE; BETA-THALASSEMIA; GENE; LET-7; PROTEINS;
IDENTIFICATION; TRANSCRIPTION; ERYTHROCYTES; HYDROXYUREA; DETERMINES
AB Induction of fetal hemoglobin (HbF) has therapeutic importance for patients with beta-hemoglobin disorders. Previous studies showed that let-7 microRNAs (miRNAs) are highly regulated in erythroid cells during the fetal-to-adult developmental transition, and that targeting let-7 mediated the up-regulation of HbF to greater than 30% of the total globin levels in human adult cultured erythroblasts. HMGA2 is a member of the high-mobility group A family of proteins and a validated target of the let-7 family of miRNAs. Here we investigate whether expression of HMGA2 directly regulates fetal hemoglobin in adult erythroblasts. Let-7 resistant HMGA2 expression was studied after lentiviral transduction of CD34(+) cells. The transgene was regulated by the erythroid-specific gene promoter region of the human SPTA1 gene (HMGA2-OE). HMGA2-OE caused significant increases in gamma-globin mRNA expression and HbF to around 16% of the total hemoglobin levels compared to matched control transductions. Interestingly, no significant changes in KLF1, SOX6, GATA1, ZBTB7A and BCL11A mRNA levels were observed. Overall, our data suggest that expression of HMGA2, a downstream target of let-7 miRNAs, causes moderately increased gamma-globin gene and protein expression in adult human erythroblasts.
C1 [de Vasconcellos, Jaira F.; Lee, Y. Terry; Byrnes, Colleen; Rebel, Antoinette; Miller, Jeffery L.] NIDDK, Mol Genom & Therapeut Sect, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA.
[Tumburu, Laxminath] NIDDK, Mol Med Branch, NIH, Bethesda, MD 20892 USA.
[Tumburu, Laxminath] NHLBI, Sickle Cell Branch, NIH, Bldg 10, Bethesda, MD 20892 USA.
RP Miller, JL (reprint author), NIDDK, Mol Genom & Therapeut Sect, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA.
EM jm7f@nih.gov
FU Intramural Research Program of the National Institute of Diabetes and
Digestive and Kidney Diseases
FX The Intramural Research Program of the National Institute of Diabetes
and Digestive and Kidney Diseases supported this work.
NR 42
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U1 5
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PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD NOV 18
PY 2016
VL 11
IS 11
AR e0166928
DI 10.1371/journal.pone.0166928
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EC7WC
UT WOS:000388350300134
PM 27861570
ER
PT J
AU Persi, E
Wolf, YI
Koonin, EV
AF Persi, Erez
Wolf, Yuri I.
Koonin, Eugene V.
TI Positive and strongly relaxed purifying selection drive the evolution of
repeats in proteins
SO NATURE COMMUNICATIONS
LA English
DT Article
ID AMINO-ACID REPEATS; NUCLEAR-PORE COMPLEX; TANDEM REPEATS; ZINC FINGERS;
REPETITIVE DNA; ANKYRIN REPEAT; EUKARYOTES; SEQUENCES; GENE;
CONSERVATION
AB Protein repeats are considered hotspots of protein evolution, associated with acquisition of new functions and novel phenotypic traits, including disease. Paradoxically, however, repeats are often strongly conserved through long spans of evolution. To resolve this conundrum, it is necessary to directly compare paralogous (horizontal) evolution of repeats within proteins with their orthologous (vertical) evolution through speciation. Here we develop a rigorous methodology to identify highly periodic repeats with significant sequence similarity, for which evolutionary rates and selection (dN/dS) can be estimated, and systematically characterize their evolution. We show that horizontal evolution of repeats is markedly accelerated compared with their divergence from orthologues in closely related species. This observation is universal across the diversity of life forms and implies a biphasic evolutionary regime whereby new copies experience rapid functional divergence under combined effects of strongly relaxed purifying selection and positive selection, followed by fixation and conservation of each individual repeat.
C1 [Persi, Erez; Wolf, Yuri I.; Koonin, Eugene V.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
RP Persi, E; Koonin, EV (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
EM erezpersi@gmail.com; koonin@ncbi.nlm.nih.gov
FU intramural funds of the US Department of Health and Human Services
FX We thank Koonin group members for useful discussions. Our research is
supported by intramural funds of the US Department of Health and Human
Services (to the National Library of Medicine).
NR 70
TC 0
Z9 0
U1 2
U2 2
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2041-1723
J9 NAT COMMUN
JI Nat. Commun.
PD NOV 18
PY 2016
VL 7
AR 13570
DI 10.1038/ncomms13570
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EC2ZS
UT WOS:000387994100002
PM 27857066
ER
PT J
AU Gibbs, KD
Basson, J
Xierali, IM
Broniatowski, DA
AF Gibbs, Kenneth D., Jr.
Basson, Jacob
Xierali, Imam M.
Broniatowski, David A.
TI Decoupling of the minority PhD talent pool and assistant professor
hiring in medical school basic science departments in the US
SO ELIFE
LA English
DT Article
ID NATIONAL-INSTITUTES; BIOMEDICAL-RESEARCH; RESEARCH WORKFORCE; RESEARCH
AWARDS; DIVERSITY; HEALTH; RACE; ETHNICITY; WOMEN; REPRESENTATION
AB Faculty diversity is a longstanding challenge in the US. However, we lack a quantitative and systemic understanding of how the career transitions into assistant professor positions of PhD scientists from underrepresented minority (URM) and well-represented (WR) racial/ethnic backgrounds compare. Between 1980 and 2013, the number of PhD graduates from URM backgrounds increased by a factor of 9.3, compared with a 2.6-fold increase in the number of PhD graduates from WR groups. However, the number of scientists from URM backgrounds hired as assistant professors in medical school basic science departments was not related to the number of potential candidates (R-2 = 0.12, p>0.07), whereas there was a strong correlation between these two numbers for scientists from WR backgrounds (R-2 = 0.48, p<0.0001). We built and validated a conceptual system dynamics model based on these data that explained 79% of the variance in the hiring of assistant professors and posited no hiring discrimination. Simulations show that, given current transition rates of scientists from URM backgrounds to faculty positions, faculty diversity would not increase significantly through the year 2080 even in the context of an exponential growth in the population of PhD graduates from URM backgrounds, or significant increases in the number of faculty positions. Instead, the simulations showed that diversity increased as more postdoctoral candidates from URM backgrounds transitioned onto the market and were hired.
C1 [Gibbs, Kenneth D., Jr.; Basson, Jacob] NIGMS, Off Program Planning Anal & Evaluat, Bethesda, MD 20892 USA.
[Xierali, Imam M.] Assoc Amer Med Coll, Publ Hlth & Divers Initiat, Washington, DC USA.
[Broniatowski, David A.] George Washington Univ, Dept Engn Management & Syst Engn, Washington, DC USA.
RP Gibbs, KD (reprint author), NIGMS, Off Program Planning Anal & Evaluat, Bethesda, MD 20892 USA.
EM kgibbsjr@gmail.com
OI Basson, Jacob/0000-0002-0521-3078; Broniatowski,
David/0000-0002-3302-9497; Gibbs, Kenneth/0000-0002-3532-5396
NR 61
TC 2
Z9 2
U1 2
U2 2
PU ELIFE SCIENCES PUBLICATIONS LTD
PI CAMBRIDGE
PA SHERATON HOUSE, CASTLE PARK, CAMBRIDGE, CB3 0AX, ENGLAND
SN 2050-084X
J9 ELIFE
JI eLife
PD NOV 17
PY 2016
VL 5
AR e21393
DI 10.7554/eLife.21393
PG 20
WC Biology
SC Life Sciences & Biomedicine - Other Topics
GA EG1PU
UT WOS:000390805500001
ER
PT J
AU Abera, MB
Xiao, JB
Nofziger, J
Titus, S
Southall, N
Zheng, W
Moritz, KE
Ferrer, M
Cherry, JJ
Androphy, EJ
Wang, A
Xu, X
Austin, C
Fischbeck, KH
Marugan, JJ
Burnett, BG
AF Abera, Mahlet B.
Xiao, Jingbo
Nofziger, Jonathan
Titus, Steve
Southall, Noel
Zheng, Wei
Moritz, Kasey E.
Ferrer, Marc
Cherry, Jonathan J.
Androphy, Elliot J.
Wang, Amy
Xu, Xin
Austin, Christopher
Fischbeck, Kenneth H.
Marugan, Juan J.
Burnett, Barrington G.
TI ML372 blocks SMN ubiquitination and improves spinal muscular atrophy
pathology in mice
SO JCI INSIGHT
LA English
DT Article
ID SMALL-MOLECULE INHIBITORS; PROTEIN-PROTEIN INTERACTION; SURVIVAL
MOTOR-NEURON; MOUSE MODEL; SINGLE NUCLEOTIDE; INCREASES SMN; PHENOTYPE;
CANCER; RESCUE; GENE
AB Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disease and one of the leading inherited causes of infant mortality. SMA results from insufficient levels of the survival motor neuron (SMN) protein, and studies in animal models of the disease have shown that increasing SMN protein levels ameliorates the disease phenotype. Our group previously identified and optimized a new series of small molecules, with good potency and toxicity profiles and reasonable pharmacokinetics, that were able to increase SMN protein levels in SMA patient-derived cells. We show here that ML372, a representative of this series, almost doubles the half-life of residual SMN protein expressed from the SMN2 locus by blocking its ubiquitination and subsequent degradation by the proteasome. ML372 increased SMN protein levels in muscle, spinal cord, and brain tissue of SMA mice. Importantly, ML372 treatment improved the righting reflex and extended survival of a severe mouse model of SMA. These results demonstrate that slowing SMN degradation by selectively inhibiting its ubiquitination can improve the motor phenotype and lifespan of SMA model mice.
C1 [Abera, Mahlet B.; Moritz, Kasey E.; Burnett, Barrington G.] Uniformed Serv Univ Hlth Sci, F Edward Hebert Sch Med, Dept Anat Physiol & Genet, Bethesda, MD 20814 USA.
[Xiao, Jingbo; Titus, Steve; Southall, Noel; Zheng, Wei; Ferrer, Marc; Wang, Amy; Xu, Xin; Austin, Christopher; Marugan, Juan J.] NIH, NIH Chem Genom Ctr, Discovery Innovat, Natl Ctr Adv Translat Sci, Rockville, MD USA.
[Cherry, Jonathan J.; Androphy, Elliot J.] Indiana Univ, Sch Med, Dept Dermatol, Indianapolis, IN USA.
[Nofziger, Jonathan; Fischbeck, Kenneth H.] NINDS, Neurogenet Branch, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
RP Marugan, JJ (reprint author), 9800 Med Ctr Dr, Rockville, MD 20850 USA.; Burnett, BG (reprint author), 4301 Jones Bridge Rd, Bethesda, MD 20814 USA.
EM maruganj@mail.nih.gov; barrington.burnett@usuhs.edu
RI Zheng, Wei/J-8889-2014
OI Zheng, Wei/0000-0003-1034-0757
NR 48
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL INVESTIGATION INC
PI ANN ARBOR
PA 2015 MANCHESTER RD, ANN ARBOR, MI 48104 USA
SN 2379-3708
J9 JCI INSIGHT
JI JCI Insight
PD NOV 17
PY 2016
VL 1
IS 19
AR e88427
DI 10.1172/jci.insight.88427
PG 13
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA EE7LI
UT WOS:000389797700005
PM 27882347
ER
PT J
AU Booth, DG
Beckett, AJ
Molina, O
Samejima, I
Masumoto, H
Kouprina, N
Larionov, V
Prior, IA
Earnshaw, WC
AF Booth, Daniel G.
Beckett, Alison J.
Molina, Oscar
Samejima, Itaru
Masumoto, Hiroshi
Kouprina, Natalay
Larionov, Vladimir
Prior, Ian A.
Earnshaw, William C.
TI 3D-CLEM Reveals that a Major Portion of Mitotic Chromosomes Is Not
Chromatin
SO MOLECULAR CELL
LA English
DT Article
ID METAPHASE CHROMOSOMES; ELECTRON-MICROSCOPY; CELL-CYCLE; ORGANIZATION;
KINETOCHORE; MITOSIS; PROTEIN; FIBERS; DNA; ULTRASTRUCTURE
AB Recent studies have revealed the importance of Ki-67 and the chromosome periphery in chromosome structure and segregation, but little is known about this elusive chromosome compartment. Here we used correlative light and serial block-face scanning electron microscopy, which we term 3D-CLEM, to model the entire mitotic chromosome complement at ultra-structural resolution. Prophase chromosomes exhibit a highly irregular surface appearance with a volume smaller than metaphase chromosomes. This may be because of the absence of the periphery, which associates with chromosomes only after nucleolar disassembly later in prophase. Indeed, the nucleolar volume almost entirely accounts for the extra volume found in metaphase chromosomes. Analysis of wild-type and Ki-67-depleted chromosomes reveals that the periphery comprises 30%-47% of the entire chromosome volume and more than 33% of the protein mass of isolated mitotic chromosomes determined by quantitative proteomics. Thus, chromatin makes up a surprisingly small percentage of the total mass of metaphase chromosomes.
C1 [Booth, Daniel G.; Molina, Oscar; Samejima, Itaru; Earnshaw, William C.] Univ Edinburgh, Inst Cell Biol, Wellcome Trust Ctr Cell Biol, Edinburgh EH9 3BF, Midlothian, Scotland.
[Masumoto, Hiroshi] Kazusa DNA Res Inst, Lab Cell Engn, Dept Frontier Res, Kisarazu, Chiba 2920818, Japan.
[Kouprina, Natalay; Larionov, Vladimir] NCI, Dev Therapeut Branch, NIH, Bethesda, MD 20892 USA.
[Beckett, Alison J.; Prior, Ian A.] Univ Liverpool, Inst Translat Med, Div Cellular & Mol Physiol, Biomed Electron Microscopy Unit, Crown St, Liverpool L69 3BX, Merseyside, England.
RP Booth, DG; Earnshaw, WC (reprint author), Univ Edinburgh, Inst Cell Biol, Wellcome Trust Ctr Cell Biol, Edinburgh EH9 3BF, Midlothian, Scotland.
EM daniel.booth@ed.ac.uk; bill.earnshaw@ed.ac.uk
OI Prior, Ian/0000-0002-4055-5161
FU Wellcome Trust [073915, 077707, 092076]; NWCR
FX We thank Leonid Mirny for helpful discussions and suggestions. This work
was supported by The Wellcome Trust, of which W.C.E. is a Principal
Research Fellow (grant number 073915). I.A.P. gratefully acknowledges
support from NWCR. The Wellcome Trust Centre for Cell Biology is
supported by Wellcome Trust core grants 077707 and 092076.
NR 58
TC 0
Z9 0
U1 0
U2 0
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1097-2765
EI 1097-4164
J9 MOL CELL
JI Mol. Cell
PD NOV 17
PY 2016
VL 64
IS 4
BP 790
EP 802
DI 10.1016/j.molcel.2016.10.009
PG 13
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA EE3RR
UT WOS:000389515400015
PM 27840028
ER
PT J
AU Woroniecki, RP
Ng, DK
Limou, S
Winkler, CA
Reidy, KJ
Mitsnefes, M
Sampson, MG
Wong, CS
Warady, BA
Furth, SL
Kopp, JB
Kaskel, FJ
AF Woroniecki, Robert P.
Ng, Derek K.
Limou, Sophie
Winkler, Cheryl A.
Reidy, Kimberly J.
Mitsnefes, Mark
Sampson, Matthew G.
Wong, Craig S.
Warady, Bradley A.
Furth, Susan L.
Kopp, Jeffrey B.
Kaskel, Frederick J.
TI Renal and Cardiovascular Morbidities Associated with APOL1 Status among
African-American and Non-African-American Children with Focal Segmental
Glomerulosclerosis
SO FRONTIERS IN PEDIATRICS
LA English
DT Article
DE cardiovascular; left ventricular hypertrophy; chronic renal disease;
FSGS; children
ID CHRONIC KIDNEY-DISEASE; LEFT-VENTRICULAR HYPERTROPHY; MARGINAL
STRUCTURAL MODELS; GENETIC-VARIANTS; BLOOD-PRESSURE; HYPERTENSION;
PROGRESSION; RISK; NEPHROPATHY; EPIDEMIOLOGY
AB Background and objectives: African-American (AA) children with focal segmental glomerulosclerosis (FSGS) have later onset disease that progresses more rapidly than in non-AA children. It is unclear how APOL1 genotypes contribute to kidney disease risk, progression, and cardiovascular morbidity in children.
Design, setting, participants, and measurements: We examined the prevalence of APOL1 genotypes and associated cardiovascular phenotypes among children with FSGS in the Chronic Kidney Disease in Children (CKiD) study; an ongoing multicenter prospective cohort study of children aged 1-16 years with mild to moderate kidney disease.
Results: A total of 140 AA children in the CKiD study were genotyped. High risk (HR) APOL1 genotypes were present in 24% of AA children (33/140) and were associated with FSGS, p < 0.001. FSGS was the most common cause of glomerular disease in children with HR APOL1 (89%; 25/28). Of 32 AA children with FSGS, 25 (78%) had HR APOL1. Compared to children with low risk APOL1 and FSGS (comprising 36 non-AA and 7 AA), children with HR APOL1 developed FSGS at a later age, 12.0 (IQR: 9.5, 12.5) vs. 5.5 (2.5, 11.5) years, p = 0.004, had a higher prevalence of uncontrolled hypertension (52 vs. 33%, p = 0.13), left ventricular hypertrophy (LVH) (53 vs. 12%, p < 0.01), C-reactive protein > 3 mg/l (33 vs. 15%, p = 0.12), and obesity (48 vs. 19%, p = 0.01). There were no differences in glomerular filtration rate, hemoglobin, iPTH, or calcium-phosphate product.
Conclusion: AA children with HR APOL1 genotype and FSGS have increase prevalence of obesity and LVH despite a later age of FSGS onset, while adjusting for socioeconomic status. Treatment of obesity may be an important component of chronic kidney disease and LVH management in this population.
C1 [Woroniecki, Robert P.] Stony Brook Childrens Hosp, Stony Brook, NY 11794 USA.
[Ng, Derek K.] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA.
[Limou, Sophie; Winkler, Cheryl A.] NCI, Basic Res Lab, Frederick Natl Lab, NIH,Leidos Biomed, Frederick, MD 21701 USA.
[Reidy, Kimberly J.; Kaskel, Frederick J.] Childrens Hosp Montefiore, Pediat Nephrol, Bronx, NY USA.
[Mitsnefes, Mark] Cincinnati Childrens Hosp Med Ctr, Div Nephrol & Hypertens, Cincinnati, OH 45229 USA.
[Sampson, Matthew G.] Univ Michigan, Sch Med, Div Pediat Nephrol, Ann Arbor, MI USA.
[Wong, Craig S.] Univ New Mexico, Pediat Nephrol, Albuquerque, NM 87131 USA.
[Warady, Bradley A.] Childrens Mercy Hosp, Div Pediat Nephrol, Kansas City, MO 64108 USA.
[Furth, Susan L.] Univ Penn, Philadelphia, PA 19104 USA.
[Kopp, Jeffrey B.] NIDDK, NIH, Bethesda, MD 20892 USA.
RP Woroniecki, RP (reprint author), Stony Brook Childrens Hosp, Stony Brook, NY 11794 USA.
EM robert.woroniecki@stonybrookmedicine.edu
FU NCATS NIH HHS [UL1 TR001425, UL1 TR001073]
NR 28
TC 0
Z9 0
U1 1
U2 1
PU FRONTIERS MEDIA SA
PI LAUSANNE
PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015,
SWITZERLAND
SN 2296-2360
J9 FRONT PEDIATR
JI Front. Pediatr.
PD NOV 17
PY 2016
VL 4
AR 122
DI 10.3389/fped.2016.00122
PG 9
WC Pediatrics
SC Pediatrics
GA EC6IP
UT WOS:000388240000001
PM 27900314
ER
PT J
AU Bloomfield, MAP
Ashok, AH
Volkow, ND
Howes, OD
AF Bloomfield, Michael A. P.
Ashok, Abhishekh H.
Volkow, Nora D.
Howes, Oliver D.
TI The effects of Delta(9)-tetrahydrocannabinol on the dopamine system
SO NATURE
LA English
DT Review
ID D-2/D-3 RECEPTOR AVAILABILITY; POSITRON-EMISSION-TOMOGRAPHY; MARIJUANA
SMOKE EXPOSURE; NUCLEUS-ACCUMBENS SHELL; CHRONIC CANNABIS USERS; IN-VIVO
MICRODIALYSIS; FREELY-MOVING RATS; WORKING-MEMORY; PREFRONTAL CORTEX;
OPIOID RECEPTORS
AB The effects of Delta(9)-tetrahydrocannabinol (THC), the main psychoactive ingredient in cannabis, are a pressing concern for global mental health. Patterns of cannabis use are changing drastically owing to legalization, the availability of synthetic analogues (commonly termed spice), cannavaping and an emphasis on the purported therapeutic effects of cannabis. Many of the reinforcing effects of THC are mediated by the dopamine system. Owing to the complexity of the cannabinoid-dopamine interactions that take place, there is conflicting evidence from human and animal studies concerning the effects of THC on the dopamine system. Acute THC administration causes increased dopamine release and neuron activity, whereas long-term use is associated with blunting of the dopamine system. Future research must examine the long-term and developmental dopaminergic effects of THC.
C1 [Bloomfield, Michael A. P.; Ashok, Abhishekh H.; Howes, Oliver D.] Imperial Coll London, Inst Clin Sci, Hammersmith Hosp, Psychiat Imaging Grp,Robert Steiner MR Unit,MRC C, London W12 0NN, England.
[Bloomfield, Michael A. P.; Ashok, Abhishekh H.; Howes, Oliver D.] Imperial Coll London, Inst Clin Sci, Psychiat Imaging Grp, Fac Med, Du Cane Rd, London W12 0NN, England.
[Bloomfield, Michael A. P.] UCL, Div Psychiat, 6th Floor,Maple House,149 Tottenham Court Rd, London WC1T 7NF, England.
[Bloomfield, Michael A. P.; Ashok, Abhishekh H.; Howes, Oliver D.] Kings Coll London, Inst Psychiat Psychol & Neurosci, Dept Psychosis Studies, De Crespigny Pk, London SE5 8AF, England.
[Bloomfield, Michael A. P.] UCL, Clin Psychopharmacol Unit, Res Dept Clin Educ & Hlth Psychol, 1-19 Torrington Pl, London WC1E 6BT, England.
[Volkow, Nora D.] NIDA, NIH, 6001 Execut Blvd, Bethesda, MD 20892 USA.
RP Howes, OD (reprint author), Imperial Coll London, Inst Clin Sci, Hammersmith Hosp, Psychiat Imaging Grp,Robert Steiner MR Unit,MRC C, London W12 0NN, England.; Howes, OD (reprint author), Imperial Coll London, Inst Clin Sci, Psychiat Imaging Grp, Fac Med, Du Cane Rd, London W12 0NN, England.; Howes, OD (reprint author), Kings Coll London, Inst Psychiat Psychol & Neurosci, Dept Psychosis Studies, De Crespigny Pk, London SE5 8AF, England.
EM oliver.howes@csc.mrc.ac.uk
FU Medical Research Council (UK) [MC-A656-5QD30]
FX We thank V. M. Rajagopal and Nature for assistance with illustrations.
This work was funded by a Medical Research Council (UK) Grant to O.D.H.
(MC-A656-5QD30).
NR 137
TC 0
Z9 0
U1 32
U2 32
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 17
PY 2016
VL 539
IS 7629
BP 369
EP 377
DI 10.1038/nature20153
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EC5GP
UT WOS:000388161700043
PM 27853201
ER
PT J
AU Witherspoon, JW
Meilleur, KG
AF Witherspoon, Jessica W.
Meilleur, Katherine G.
TI Review of RyR1 pathway and associated pathomechanisms
SO ACTA NEUROPATHOLOGICA COMMUNICATIONS
LA English
DT Review
DE RyR1; Myopathies; Skeletal; Muscle; Oxidative; Stress;
Excitation-contraction; Pathomechanism; Treatment; Mitochondria;
Post-translational modifications
ID MUSCLE RYANODINE RECEPTOR; CENTRAL CORE DISEASE; CALCIUM-RELEASE
CHANNELS; CONGENITAL NEUROMUSCULAR DISEASE; KING-DENBOROUGH-SYNDROME;
COUPLED REDOX REGULATION; CYTOCHROME-C-OXIDASE; UNIFORM TYPE-1 FIBER;
KNOCK-IN MICE; II-III LOOP
AB Ryanodine receptor isoform-1 (RyR1) is a major calcium channel in skeletal muscle important for excitation-contraction coupling. Mutations in the RYR1 gene yield RyR1 protein dysfunction that manifests clinically as RYR1-related congenital myopathies (RYR1-RM) and/or malignant hyperthermia susceptibility (MHS). Individuals with RYR1-RM and/or MHS exhibit varying symptoms and severity. The symptoms impair quality of life and put patients at risk for early mortality, yet the cause of varying severity is not well understood. Currently, there is no Food and Drug Administration (FDA) approved treatment for RYR1-RM. Discovery of effective treatments is therefore critical, requiring knowledge of the RyR1 pathway. The purpose of this review is to compile work published to date on the RyR1 pathway and to implicate potential regions as targets for treatment. The RyR1 pathway is comprised of protein-protein interactions, protein-ligand interactions, and post-translational modifications, creating an activation/regulatory macromolecular complex. Given the complexity of this pathway, we divided these interactions and modifications into six regulatory groups. Three of several RyR1 interacting proteins, FK506-binding protein 12 (FKBP12), triadin, and calmodulin, were identified as playing important roles across all groups and may serve as promising target sites for treatment. Also, variability in disease severity may be influenced by prolongation or hyperactivity of post-translational modifications resulting from RyR1 dysfunction.
C1 [Witherspoon, Jessica W.; Meilleur, Katherine G.] NINR, Tissue Injury Branch, Neuromuscular Symptoms Unit, NIH, Bethesda, MD 20814 USA.
RP Witherspoon, JW (reprint author), NINR, Tissue Injury Branch, Neuromuscular Symptoms Unit, NIH, Bethesda, MD 20814 USA.
EM jessica.witherspoon@nih.gov
NR 159
TC 0
Z9 0
U1 7
U2 7
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 2051-5960
J9 ACTA NEUROPATHOL COM
JI Acta Neuropathol. Commun.
PD NOV 17
PY 2016
VL 4
AR 121
DI 10.1186/s40478-016-0392-6
PG 20
WC Neurosciences
SC Neurosciences & Neurology
GA EC2BT
UT WOS:000387915100001
PM 27855725
ER
PT J
AU Anderson, ED
Gorka, AP
Schnermann, MJ
AF Anderson, Erin D.
Gorka, Alexander P.
Schnermann, Martin J.
TI Near-infrared uncaging or photosensitizing dictated by oxygen tension
SO NATURE COMMUNICATIONS
LA English
DT Article
ID PHOTODYNAMIC THERAPY; ELECTRON-TRANSFER; PHTHALOCYANINE
PHOTOSENSITIZERS; SULFONATED PHTHALOCYANINES; SILICON PHTHALOCYANINES;
METAL PHTHALOCYANINES; AQUEOUS-SOLUTIONS; TUMOR HYPOXIA; CELL-DEATH;
LIGHT
AB Existing strategies that use tissue-penetrant near-infrared light for the targeted treatment of cancer typically rely on the local generation of reactive oxygen species. This approach can be impeded by hypoxia, which frequently occurs in tumour microenvironments. Here we demonstrate that axially unsymmetrical silicon phthalocyanines uncage small molecules preferentially in a low-oxygen environment, while efficiently generating reactive oxygen species in normoxic conditions. Mechanistic studies of the uncaging reaction implicate a photoredox pathway involving photoinduced electron transfer to generate a key radical anion intermediate. Cellular studies demonstrate that the biological mechanism of action is O-2-dependent, with reactive oxygen species-mediated phototoxicity in normoxic conditions and small molecule uncaging in hypoxia. These studies provide a near-infrared light-targeted treatment strategy with the potential to address the complex tumour landscape through two distinct mechanisms that vary in response to the local O-2 environment.
C1 [Anderson, Erin D.; Gorka, Alexander P.; Schnermann, Martin J.] NCI, Biol Chem Lab, Ctr Canc Res, Frederick, MD 21702 USA.
RP Schnermann, MJ (reprint author), NCI, Biol Chem Lab, Ctr Canc Res, Frederick, MD 21702 USA.
EM martin.schnermann@nih.gov
FU Intramural Research Program of the National Institutes of Health, Center
for Cancer Research; National Cancer Institute, National Institutes of
Health
FX We thank the Optical Microscopy and Analysis Laboratory (Advanced
Technology Program, Frederick National Laboratory for Cancer Research)
for assistance in obtaining confocal fluorescence images and the
Frederick Center for Cancer Research Flow Cytometry Core (Cancer and
Inflammation Program, NCI-Frederick) for help with the cell cycle
analysis. We thank Dr Joseph Barchi for NMR assistance and Dr James
Kelley for mass spectrometric analysis. Drs Hisataka Kobayashi and
Murali Krishna are gratefully acknowledged for assistance with hypoxia
experiments and insightful comments. Ms Luxi Qiao is acknowledged for
assistance with initial synthetic studies. This work was supported by
the Intramural Research Program of the National Institutes of Health,
Center for Cancer Research and the National Cancer Institute, National
Institutes of Health.
NR 56
TC 0
Z9 0
U1 35
U2 35
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2041-1723
J9 NAT COMMUN
JI Nat. Commun.
PD NOV 17
PY 2016
VL 7
AR 13378
DI 10.1038/ncomms13378
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EC5CG
UT WOS:000388150100001
PM 27853134
ER
PT J
AU Zarin, DA
Tse, T
Williams, RJ
Carr, S
AF Zarin, Deborah A.
Tse, Tony
Williams, Rebecca J.
Carr, Sarah
TI Trial Reporting in ClinicalTrials.gov - The Final Rule
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID REGISTRATION; ISSUES
C1 [Zarin, Deborah A.; Tse, Tony; Williams, Rebecca J.] NIH, Natl Lib Med, Bldg 10, Bethesda, MD 20892 USA.
[Carr, Sarah] NIH, Off Sci Policy, Bldg 10, Bethesda, MD 20892 USA.
RP Zarin, DA (reprint author), NIH, Natl Lib Med, Bldg 10, Bethesda, MD 20892 USA.
FU Intramural NIH HHS [Z99 LM999999]
NR 15
TC 7
Z9 7
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 NOV 17
PY 2016
VL 375
IS 20
BP 1998
EP 2004
DI 10.1056/NEJMsr1611785
PG 7
WC Medicine, General & Internal
SC General & Internal Medicine
GA EC1HS
UT WOS:000387856100015
PM 27635471
ER
PT J
AU Wyss, AB
Jones, AC
Bolling, AK
Kissling, GE
Chartier, R
Dahlman, HJ
Rodes, CE
Archer, J
Thornburg, J
Schwarze, PE
London, SJ
AF Wyss, Annah B.
Jones, Anna Ciesielski
Bolling, Anette K.
Kissling, Grace E.
Chartier, Ryan
Dahlman, Hans Jorgen
Rodes, Charles E.
Archer, Janet
Thornburg, Jonathan
Schwarze, Per E.
London, Stephanie J.
TI Particulate Matter 2.5 Exposure and Self-Reported Use of Wood Stoves and
Other Indoor Combustion Sources in Urban Nonsmoking Homes in Norway
SO PLOS ONE
LA English
DT Article
ID AIR-QUALITY; OUTDOOR; PM2.5; CHANGEOUT; PROGRAM
AB Few studies have examined particulate matter (PM) exposure from self-reported use of wood stoves and other indoor combustion sources in urban settings in developed countries. We measured concentrations of indoor PM < 2.5 microns (PM2.5) for one week with the MicroPEM (TM) nephelometer in 36 households in the greater Oslo, Norway metropolitan area. We examined indoor PM2.5 levels in relation to use of wood stoves and other combustion sources during a 7 day monitoring period using mixed effects linear models with adjustment for ambient PM2.5 levels. Mean hourly indoor PM2.5 concentrations were higher (p = 0.04) for the 14 homes with wood stove use (15.6 mu g/m(3)) than for the 22 homes without (12.6 mu g/m(3)). Moreover, mean hourly PM2.5 was higher (p = 0.001) for use of wood stoves made before 1997 (6 homes, 20.2 mu g/m(3)), when wood stove emission limits were instituted in Norway, compared to newer wood stoves (8 homes, 11.9 mu g/m(3)) which had mean hourly values similar to control homes. Increased PM2.5 levels during diary-reported burning of candles was detected independently of concomitant wood stove use. These results suggest that self-reported use of wood stoves, particularly older stoves, and other combustion sources, such as candles, are associated with indoor PM2.5 measurements in an urban population from a high income country.
C1 [Wyss, Annah B.; Kissling, Grace E.; London, Stephanie J.] NIEHS, Div Intramural Res, NIH, US Dept Hlth & Human Serv, POB 12233, Res Triangle Pk, NC 27709 USA.
[Jones, Anna Ciesielski; Archer, Janet] Social & Sci Syst Inc, Durham, NC USA.
[Bolling, Anette K.; Dahlman, Hans Jorgen; Schwarze, Per E.] Norwegian Inst Publ Hlth, Domain Infect Control & Environm Hlth, Dept Air Pollut & Noise, Oslo, Norway.
[Chartier, Ryan; Rodes, Charles E.; Thornburg, Jonathan] Res Triangle Inst Int, Res Triangle Pk, NC USA.
RP London, SJ (reprint author), NIEHS, Div Intramural Res, NIH, US Dept Hlth & Human Serv, POB 12233, Res Triangle Pk, NC 27709 USA.
EM london2@niehs.nih.gov
OI London, Stephanie/0000-0003-4911-5290
FU Intramural Research Program of the NIH, National Institute of
Environmental Health Sciences [ZIA ES049019]; NIEHS; RTI
FX This research was supported by the Intramural Research Program of the
NIH, National Institute of Environmental Health Sciences (ZIA ES049019).
Anna Ciesielski Jones and Janet Archer are employed by Social &
Scientific Systems, Inc., which serves as a contractor to the National
Institutes of Health. The support for their effort on this project is
provided via contract with NIEHS. Ryan Chartier and Jonathan Thornburg
are employed by Research Triangle Institute International, a non-profit
organization. RTI provided support in the form of salaries for these
authors. Neither RTI nor SSS had any additional role in the study
design, data collection and analysis, decision to publish, or
preparation of the manuscript. The specific roles of these authors are
articulated in the 'author contributions' section.
NR 20
TC 0
Z9 0
U1 13
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 NOV 17
PY 2016
VL 11
IS 11
AR e0166440
DI 10.1371/journal.pone.0166440
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EC2AC
UT WOS:000387910200032
PM 27855223
ER
PT J
AU Varsano, N
Dadosh, T
Kapishnikov, S
Pereiro, E
Shimoni, E
Jin, XT
Kruth, HS
Leiserowitz, L
Addadi, L
AF Varsano, Neta
Dadosh, Tali
Kapishnikov, Sergey
Pereiro, Eva
Shimoni, Eyal
Jin, Xueting
Kruth, Howard S.
Leiserowitz, Leslie
Addadi, Lia
TI Development of Correlative Cryo-soft X-ray Tomography and Stochastic
Reconstruction Microscopy. A Study of Cholesterol Crystal Early
Formation in Cells
SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Article
ID HUMAN ATHEROSCLEROTIC LESIONS; DIGESTIVE VACUOLE MEMBRANE; MACROPHAGE
FOAM CELLS; UNESTERIFIED CHOLESTEROL; CRYOELECTRON TOMOGRAPHY;
PLASMODIUM-FALCIPARUM; SUPPORTED MEMBRANES; PLASMA-MEMBRANE;
FLUORESCENCE; TRANSPORT
AB We have developed a high resolution correlative method involving cryo-soft X-ray tomography (cryo-SXT) and stochastic optical reconstruction microscopy (STORM), which provides information in three dimensions on large cellular volumes at 70 nm resolution. Cryo-SXT morphologically identified and localized aggregations of carbon-rich materials. STORM identified specific markers on the desired epitopes, enabling colocalization between the identified objects, in this case cholesterol crystals, and the cellular environment. The samples were studied under ambient and cryogenic conditions without dehydration or heavy metal staining. The early events of cholesterol crystal development were investigated in relation to atherosclerosis, using as model macrophage cell cultures enriched with LDL particles. Atherosclerotic plaques build up in arteries in a slow process involving cholesterol crystal accumulation. Cholesterol crystal deposition is a crucial stage in the pathological cascade. Our results show that cholesterol crystals can be identified and imaged at a very early stage on the cell plasma membrane and in intracellular locations. This technique can in principle be applied to other biological samples where specific molecular identification is required in conjunction with high resolution 3D-imaging.
C1 [Varsano, Neta; Addadi, Lia] Weizmann Inst Sci, Dept Struct Biol, IL-76100 Rehovot, Israel.
[Dadosh, Tali; Shimoni, Eyal] Weizmann Inst Sci, Dept Chem Res Support, IL-76100 Rehovot, Israel.
[Leiserowitz, Leslie] Weizmann Inst Sci, Dept Mat & Interfaces, IL-76100 Rehovot, Israel.
[Kapishnikov, Sergey] Helmholtz Zentrum Berlin, Soft Matter & Funct Mat, Albert Einstein Str 15, D-12489 Berlin, Germany.
[Pereiro, Eva] ALBA Synchrotron Light Source, MISTRAL Beamline Expt Div, Barcelona 08290, Spain.
[Jin, Xueting; Kruth, Howard S.] NHLBI, Expt Atherosclerosis Sect, NIH, Bldg 10, Bethesda, MD 20892 USA.
RP Addadi, L (reprint author), Weizmann Inst Sci, Dept Struct Biol, IL-76100 Rehovot, Israel.
EM sergey.kapishnikov@nbi.ku.dk; lia.addadi@weizmann.ac.il
FU European Community's Seventh Framework Programme [283570]; Binational
Science Foundation [2013045]
FX We thank Prof. Benjamin Geiger and Michal Shemesh for their support in
the cell culture growth and maintenance. We thank Dr. Sharon G. Wolf for
her help with freezing and handling cryo-samples and for many fruitful
discussions. We thank Helena Sabanay for her help and guidance with the
TEM sample preparation. We thank Moshe Varsano for his great help with
programming. Super-resolution microscopy was performed at the Irving and
Cherna Moskowitz Center for Nano and Bio-Nano Imaging at the Weizmann
Institute of Science. Cryo-SXT experiments were performed at MISTRAL
beamline at ALBA Synchrotron with the collaboration of ALBA staff. The
research leading to these results has received funding from the European
Community's Seventh Framework Programme (FP7/2007-2013) under grant
agreement no. 283570. This research was supported by the Binational
Science Foundation (grant 2013045 to L.A. and H.S.K.). L.A. is the
incumbent of the Dorothy and Patrick Gorman Professorial Chair of
Biological Ultrastructure at the Weizmann Institute of Science.
NR 58
TC 0
Z9 0
U1 7
U2 7
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0002-7863
J9 J AM CHEM SOC
JI J. Am. Chem. Soc.
PD NOV 16
PY 2016
VL 138
IS 45
BP 14931
EP 14940
DI 10.1021/jacs.6b07584
PG 10
WC Chemistry, Multidisciplinary
SC Chemistry
GA EC8YE
UT WOS:000388428200022
PM 27934213
ER
PT J
AU Wang, Z
Zhang, FW
Wang, ZT
Liu, YJ
Fu, X
Jin, A
Yung, BC
Chen, W
Fan, J
Yang, XY
Niu, G
Chen, XY
AF Wang, Zhe
Zhang, Fuwu
Wang, Zhantong
Liu, Yijing
Fu, Xiao
Jin, Albert
Yung, Bryant C.
Chen, Wei
Fan, Jing
Yang, Xiangyu
Niu, Gang
Chen, Xiaoyuan
TI Hierarchical Assembly of Bioactive Amphiphilic Molecule Pairs into
Supramolecular Nanofibril Self-Supportive Scaffolds for Stem Cell
Differentiation
SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Article
ID NEURAL STEM; DEGRADABLE HYDROGELS; SUBVENTRICULAR ZONE; NEURITE
OUTGROWTH; SYNAPSE FORMATION; PROGENITOR CELLS; DENTATE GYRUS; PEPTIDE;
ACID; NANOSTRUCTURES
AB Molecular design of biomaterials with unique features recapitulating nature's niche to influence biological activities has been a prolific area of investigation in chemistry and material science. The extracellular matrix (ECM) provides a wealth of bioactive molecules in supporting cell proliferation, migration, and differentiation. The well-patterned fibril and intertwining architecture of the ECM profoundly influences cell behavior and development. Inspired by those features from the ECM, we attempted to integrate essential biological factors from the ECM to design bioactive molecules to construct artificial self-supportive ECM mimics to advance stem cell culture. The synthesized biomimic molecules are able to hierarchically self-assemble into nanofibril hydrogels in physiological buffer driven by cooperative effects of electrostatic interaction, van der Waals forces, and intermolecular hydrogen bonds. In addition, the hydrogel is designed to be degradable during cell culture, generating extra space to facilitate cell migration, expansion, and differentiation. We exploited the bioactive hydrogel as a growth factor-free scaffold to support and accelerate neural stem cell adhesion, proliferation, and differentiation into functional neurons. Our study is a successful attempt to entirely use bioactive molecules for bottom-up self-assembly of new biomaterials mimicking the ECM to directly impact cell behaviors. Our strategy provides a new avenue in biomaterial design to advance tissue engineering and cell delivery.
C1 [Wang, Zhe; Zhang, Fuwu; Wang, Zhantong; Liu, Yijing; Fu, Xiao; Yung, Bryant C.; Chen, Wei; Fan, Jing; Yang, Xiangyu; Niu, Gang; Chen, Xiaoyuan] Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD 20892 USA.
[Fu, Xiao; Jin, Albert] Natl Inst Biomed Imaging & Bioengn, Lab Cellular Imaging & Macromol Biophys, NIH, Bethesda, MD 20892 USA.
RP Chen, XY (reprint author), Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD 20892 USA.
EM Shawn.Chen@nih.gov
FU Center for Neuroscience and Regenerative Medicine (CNRM) program grant
from the Department of Defense (DoD); Intramural Research Program (IRP)
of National Institutes of Health (NIH)
FX This study was supported, in part, by the Center for Neuroscience and
Regenerative Medicine (CNRM) program grant from the Department of
Defense (DoD) and the Intramural Research Program (IRP) of National
Institutes of Health (NIH).
NR 60
TC 0
Z9 0
U1 46
U2 46
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0002-7863
J9 J AM CHEM SOC
JI J. Am. Chem. Soc.
PD NOV 16
PY 2016
VL 138
IS 45
BP 15027
EP 15034
DI 10.1021/jacs.6b09014
PG 8
WC Chemistry, Multidisciplinary
SC Chemistry
GA EC8YE
UT WOS:000388428200034
PM 27775895
ER
PT J
AU Nagy, GN
Suardiaz, R
Lopata, A
Ozohanics, O
Vekey, K
Brooks, BR
Leveles, I
Toth, J
Vertessy, BG
Rosta, E
AF Nagy, Gergely N.
Suardiaz, Reynier
Lopata, Anna
Ozohanics, Oliver
Vekey, Karoly
Brooks, Bernard R.
Leveles, Ibolya
Toth, Judit
Vertessy, Beata G.
Rosta, Edina
TI Structural Characterization of Arginine Fingers: Identification of an
Arginine Finger for the Pyrophosphatase dUTPases
SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Article
ID INFECTIOUS-ANEMIA VIRUS; MOLECULAR-DYNAMICS; ESCHERICHIA-COLI;
GTP-HYDROLYSIS; ACTIVE-SITE; LIGAND-BINDING; DCTP DEAMINASE;
FORCE-FIELD; C-TERMINUS; MECHANISM
AB Arginine finger is a highly conserved and essential residue in many GTPase and AAA+ ATPase enzymes that completes the active site from a distinct protomer, forming contacts with the gamma-phosphate of the nucleotide. To date, no pyrophosphatase has been identified that employs an arginine finger fulfilling all of the above properties; all essential arginine fingers are used to catalyze the cleavage of the gamma-phosphate. Here, we identify and unveil the role of a conserved arginine residue in trimeric dUTPases that meets all the criteria established for arginine fingers. We found that the conserved arginine adjacent to the P-loop-like motif enables structural organization of the active site for efficient catalysis via its nucleotide coordination, while its direct electrostatic role in transition state stabilization is secondary. An exhaustive structure-based comparison of analogous, conserved arginines from nucleotide hydrolases and transferases revealed a consensus amino acid location and orientation for contacting the gamma-phosphate of the substrate nucleotide. Despite the structurally equivalent position, functional differences between arginine fingers of dUTPases and NTPases are explained on the basis of the unique chemistry performed by the pyrophosphatase dUTPases.
C1 [Nagy, Gergely N.; Leveles, Ibolya; Vertessy, Beata G.] Budapest Univ Technol & Econ, Dept Biotechnol & Food Sci, H-1111 Budapest, Hungary.
[Nagy, Gergely N.; Lopata, Anna; Leveles, Ibolya; Toth, Judit; Vertessy, Beata G.] Hungarian Acad Sci, Res Ctr Nat Sci, Inst Enzymol, H-1117 Budapest, Hungary.
[Suardiaz, Reynier; Rosta, Edina] Kings Coll London, Dept Chem, London SE1 1DB, England.
[Ozohanics, Oliver] Hungarian Acad Sci, Res Ctr Nat Sci, Inst Organ Chem, MS Prote Res Grp, H-1117 Budapest, Hungary.
[Vekey, Karoly] Hungarian Acad Sci, Res Ctr Nat Sci, Core Technol Ctr, H-1117 Budapest, Hungary.
[Brooks, Bernard R.] NHLBI, Lab Computat Biol, NIH, Rockville, MD 20852 USA.
[Lopata, Anna] NHLBI, Lab Mol Physiol, NIH, Bldg 10, Bethesda, MD 20892 USA.
[Lopata, Anna] Univ Leeds, Fac Biol Sci, Astbury Ctr Struct Mol Biol, Leeds LS2 9JT, W Yorkshire, England.
[Vekey, Karoly] Szent Istvan Univ, Ybl Miklos Fac Architecture & Civil Engn, H-1442 Budapest, Hungary.
RP Nagy, GN; Vertessy, BG (reprint author), Budapest Univ Technol & Econ, Dept Biotechnol & Food Sci, H-1111 Budapest, Hungary.; Nagy, GN; Vertessy, BG (reprint author), Hungarian Acad Sci, Res Ctr Nat Sci, Inst Enzymol, H-1117 Budapest, Hungary.; Rosta, E (reprint author), Kings Coll London, Dept Chem, London SE1 1DB, England.
EM edina.rosta@kcl.ac.uk; vertessy@mail.bme.hu; edina.rosta@kcl.ac.uk
RI Suardiaz, Reynier/B-2962-2008
OI Suardiaz, Reynier/0000-0002-1035-9020
FU EPSRC [EP/L000253/1]; EC [622711]; BBSRC [BB/N007700/1]; National
Research, Development and Innovation Office Hungarian Scientific
Research Fund [OTKA K115993, K119493, K109486]; MedinProt program of the
Hungarian Academy of Sciences; International Centre for Genetic
Engineering and Biotechnology [ICGEB CRP/HUN14-01]; European Commission
FP7 Biostruct-X project [283570]; Bolyai Janos Research Scholarship of
the Hungarian Academy of Sciences
FX E.R. gratefully acknowledges Dr. Kei-ichi Okazaki for helpful
discussions, and P.G. Jambrina for help with structural alignments. We
acknowledge the European Synchrotron Radiation Facility for provision of
synchrotron radiation facilities, and we would like to thank Alexander
Popov for assistance in using beamline ID23-2. We gratefully thank
Veronika Harmat for home source and synchrothron data collection,
respectively. We acknowledge computer time on ARCHER granted via the UK
High-End Computing Consortium for Biomolecular Simulation, HECBioSim
(http://www.hecbiosim.ac.uk), supported by EPSRC (Grant EP/L000253/1)
and the computational resources of the NIH biowulf cluster. R.S.
acknowledges the EC for a Marie Curie fellowship (Project 622711). E.R
acknowledges the BB/N007700/1 BBSRC grant. This work was supported by
the National Research, Development and Innovation Office Hungarian
Scientific Research Fund [OTKA K115993, K119493, K109486], the MedinProt
program of the Hungarian Academy of Sciences, the International Centre
for Genetic Engineering and Biotechnology [ICGEB CRP/HUN14-01], and the
European Commission FP7 Biostruct-X project [Contract 283570]. J.T. is
supported by the Bolyai Janos Research Scholarship of the Hungarian
Academy of Sciences.
NR 74
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Z9 0
U1 5
U2 5
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0002-7863
J9 J AM CHEM SOC
JI J. Am. Chem. Soc.
PD NOV 16
PY 2016
VL 138
IS 45
BP 15035
EP 15045
DI 10.1021/jacs.6b09012
PG 11
WC Chemistry, Multidisciplinary
SC Chemistry
GA EC8YE
UT WOS:000388428200035
PM 27740761
ER
PT J
AU Onozawa, M
Aplan, PD
AF Onozawa, Masahiro
Aplan, Peter D.
TI Templated Sequence Insertion Polymorphisms in the Human Genome
SO FRONTIERS IN CHEMISTRY
LA English
DT Review
DE templated sequence insertion polymorphisms (TSIPs); mitochondria;
polymorphism; human migration; DNA repair; LINE-1 retrotransposon
ID INDEPENDENT LINE-1 RETROTRANSPOSITION; DOUBLE-STRAND BREAKS;
REVERSE-TRANSCRIPTASE; DNA; REPAIR; CHROMOSOMES; MITOCHONDRIA;
EVOLUTION; REPEATS; SITE
AB Templated Sequence Insertion Polymorphism (TSIP) is a recently described form of polymorphism recognized in the human genome, in which a sequence that is templated from a distant genomic region is inserted into the genome, seemingly at random. TSIPs can be grouped into two classes based on nucleotide sequence features at the insertion junctions; Class 1 TSIPs show features of insertions that are mediated via the LINE-1 ORF2 protein, including (1) target-site duplication (TSD), (2) polyadenylation 10-30 nucleotides downstream of a "cryptic" polyadenylation signal, and (3) preference for insertion at a 5'-TTTT/A-3' sequence. In contrast, class 2 TSIPs show features consistent with repair of a DNA double-strand break (DSB) via insertion of a DNA "patch" that is derived from a distant genomic region. Survey of a large number of normal human volunteers demonstrates that most individuals have 25-30 TSIPs, and that these TSIPs track with specific geographic regions. Similar to other forms of human polymorphism, we suspect that these TSIPs may be important for the generation of human diversity and genetic diseases.
C1 [Onozawa, Masahiro; Aplan, Peter D.] NCI, Genet Branch, NIH, Bethesda, MD 20892 USA.
[Onozawa, Masahiro] Hokkaido Univ, Grad Sch Med, Dept Hematol, Sapporo, Hokkaido, Japan.
RP Aplan, PD (reprint author), NCI, Genet Branch, NIH, Bethesda, MD 20892 USA.
EM aplanp@mail.nih.gov
FU intramural research program of the NCI, NIH; Japan Society for the
Promotion of Science (JSPS) [26890001, 16K09836]
FX This work was supported by the intramural research program of the NCI,
NIH. MO was supported by the Japan Society for the Promotion of Science
(JSPS), Grant-in-Aid for Research Activity Start-up (26890001) and
Grant-in-Aid for Scientific Research (C) (16K09836).
NR 38
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Z9 0
U1 4
U2 4
PU FRONTIERS MEDIA SA
PI LAUSANNE
PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015,
SWITZERLAND
EI 2296-2646
J9 FRONT CHEM
JI Front. Chem.
PD NOV 16
PY 2016
VL 4
AR 43
DI 10.3389/fchem.2016.00043
PG 7
WC Chemistry, Multidisciplinary
SC Chemistry
GA EC3IG
UT WOS:000388019100001
PM 27900318
ER
PT J
AU Guo, M
Zhang, C
Wang, Y
Feng, LH
Wang, ZP
Niu, WB
Du, XY
Tang, W
Li, YN
Wang, C
Chen, ZW
AF Guo, Meng
Zhang, Cheng
Wang, Yan
Feng, Lizhao
Wang, Zhengpin
Niu, Wanbo
Du, Xiaoyan
Tang, Wang
Li, Yuna
Wang, Chao
Chen, Zhenwen
TI Progesterone Receptor Membrane Component 1 Mediates Progesterone-Induced
Suppression of Oocyte Meiotic Prophase I and Primordial Folliculogenesis
SO SCIENTIFIC REPORTS
LA English
DT Article
ID PREMATURE OVARIAN FAILURE; MOUSE GERM-CELLS; FOLLICLE FORMATION; FETAL
OVARY; EARLY OOGENESIS; MPR-ALPHA; EXPRESSION; PGRMC1; PROTEIN; COMPLEX
AB Well-timed progression of primordial folliculogenesis is essential for mammalian female fertility. Progesterone (P4) inhibits primordial follicle formation under physiological conditions; however, P4 receptor that mediates this effect and its underlying mechanisms are unclear. In this study, we used an in vitro organ culture system to show that progesterone receptor membrane component 1 (PGRMC1) mediated P4-induced inhibition of oocyte meiotic prophase I and primordial follicle formation. We found that membrane-impermeable BSA-conjugated P4 inhibited primordial follicle formation similar to that by P4. Interestingly, PGRMC1 and its partner serpine1 mRNA-binding protein 1 were highly expressed in oocytes in perinatal ovaries. Inhibition or RNA interference of PGRMC1 abolished the suppressive effect of P4 on follicle formation. Furthermore, P4-PGRMC1 interaction blocked oocyte meiotic progression and decreased intra-oocyte cyclic AMP (cAMP) levels in perinatal ovaries. cAMP analog dibutyryl cAMP reversed P4-PGRMC1 interaction-induced inhibition of meiotic progression and follicle formation. Thus, our results indicated that PGRMC1 mediated P4-induced suppression of oocyte meiotic progression and primordial folliculogenesis by decreasing intra-oocyte cAMP levels.
C1 [Guo, Meng; Du, Xiaoyan] Capital Med Univ, Sch Basic Med Sci, Dept Lab Anim Sci, Beijing 100069, Peoples R China.
[Zhang, Cheng] Capital Normal Univ, Coll Life Sci, Beijing 100048, Peoples R China.
[Wang, Yan; Tang, Wang; Li, Yuna; Chen, Zhenwen] Capital Med Univ, Sch Basic Med Sci, Dept Med Genet & Dev Biol, Beijing 100069, Peoples R China.
[Feng, Lizhao; Niu, Wanbo; Wang, Chao] China Agr Univ, Coll Biol Sci, State Key Lab Agrobiotechnol, Beijing 100193, Peoples R China.
[Wang, Zhengpin] NIDDK, Cellular & Dev Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Chen, ZW (reprint author), Capital Med Univ, Sch Basic Med Sci, Dept Med Genet & Dev Biol, Beijing 100069, Peoples R China.; Wang, C (reprint author), China Agr Univ, Coll Biol Sci, State Key Lab Agrobiotechnol, Beijing 100193, Peoples R China.
EM wangcam@cau.edu.cn; czwenteam@163.com
FU National Natural Science Foundation of China [31402027]; Key Projects in
the National Science & Technology Pillar Program [2015BAI09B01]
FX This work was supported by the National Natural Science Foundation of
China (No. 31402027) and Key Projects in the National Science &
Technology Pillar Program (No. 2015BAI09B01).
NR 50
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Z9 0
U1 4
U2 4
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2045-2322
J9 SCI REP-UK
JI Sci Rep
PD NOV 16
PY 2016
VL 6
AR 36869
DI 10.1038/srep36869
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EC4FD
UT WOS:000388080800001
PM 27848973
ER
PT J
AU Rhee, DK
Lim, JC
Hockman, SC
Ahmad, F
Woo, DH
Chung, YW
Liu, SW
Hockman, AL
Manganiello, VC
AF Rhee, Dong Keun
Lim, Jung Chae
Hockman, Steven C.
Ahmad, Faiyaz
Woo, Dong Ho
Chung, Youn Wook
Liu, Shiwei
Hockman, Allison L.
Manganiello, Vincent C.
TI Effects of heterologous expression of human cyclic nucleotide
phosphodiesterase 3A (hPDE3A) on redox regulation in yeast
SO BIOCHEMICAL JOURNAL
LA English
DT Article
ID DEPENDENT PROTEIN-KINASE; DISULFIDE BOND FORMATION; CYSTEINE-SULFINIC
ACID; SACCHAROMYCES-CEREVISIAE; OXIDATIVE STRESS; TRANSCRIPTION FACTOR;
SIGNALING COMPLEXES; CELLULAR-RESPONSES; CAMP; PATHWAY
AB Oxidative stress plays a pivotal role in pathogenesis of cardiovascular diseases and diabetes; however, the roles of protein kinase A (PKA) and human phosphodiesterase 3A (hPDE3A) remain unknown. Here, we show that yeast expressing wild-type (WT) hPDE3A or K13R hPDE3A (putative ubiquitinylation site mutant) exhibited resistance or sensitivity to exogenous hydrogen peroxide (H2O2), respectively. H2O2-stimulated ROS production was markedly increased in yeast expressing K13R hPDE3A (Oxidative stress Sensitive 1, OxiS1), compared with yeast expressing WT hPDE3A (Oxidative stress Resistant 1, OxiR1). In OxiR1, YAP1 and YAP1-dependent antioxidant genes were up-regulated, accompanied by a reduction in thioredoxin peroxidase. In OxiS1, expression of YAP1 and YAP1-dependent genes was impaired, and the thioredoxin system malfunctioned. H2O2 increased cyclic adenosine monophosphate (cAMP)-hydrolyzing activity of WT hPDE3A, but not K13R hPDE3A, through PKA-dependent phosphorylation of hPDE3A, which was correlated with its ubiquitinylation. The changes in antioxidant gene expression did not directly correlate with differences in cAMP-PKA signaling. Despite differences in their capacities to hydrolyze cAMP, total cAMP levels among OxiR1, OxiS1, and mock were similar; PKA activity, however, was lower in OxiS1 than in OxiR1 or mock. During exposure to H2O2, however, Sch9p activity, a target of Rapamycin complex 1-regulated Rps6 kinase and negative-regulator of PKA, was rapidly reduced in OxiR1, and Tpk1p, a PKA catalytic subunit, was diffusely spread throughout the cytosol, with PKA activation. In OxiS1, Sch9p activity was unchanged during exposure to H2O2, consistent with reduced activation of PKA. These results suggest that, during oxidative stress, TOR-Sch9 signaling might regulate PKA activity, and that post-translational modifications of hPDE3A are critical in its regulation of cellular recovery from oxidative stress.
C1 [Rhee, Dong Keun; Hockman, Steven C.; Ahmad, Faiyaz; Chung, Youn Wook; Liu, Shiwei; Hockman, Allison L.; Manganiello, Vincent C.] NHLBI, Lab Biochem Physiol, Cardiovasc & Pulm Branch, NIH, Room 5N-307,Bldg 10, Bethesda, MD 20892 USA.
[Lim, Jung Chae] NHLBI, Biochem Lab, Bldg 3, Bethesda, MD 20892 USA.
[Woo, Dong Ho] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Nervous Syst Dev & Plast Sect, NIH, Bethesda, MD 20892 USA.
RP Rhee, DK (reprint author), NHLBI, Lab Biochem Physiol, Cardiovasc & Pulm Branch, NIH, Room 5N-307,Bldg 10, Bethesda, MD 20892 USA.
EM rheed2@mail.nih.gov
FU National Institutes of Health, National Heart, Lung, and Blood Institute
FX This work was supported by the Intramural Research Program, National
Institutes of Health, National Heart, Lung, and Blood Institute.
NR 64
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U2 1
PU PORTLAND PRESS LTD
PI LONDON
PA CHARLES DARWIN HOUSE, 12 ROGER STREET, LONDON WC1N 2JU, ENGLAND
SN 0264-6021
EI 1470-8728
J9 BIOCHEM J
JI Biochem. J.
PD NOV 15
PY 2016
VL 473
BP 4205
EP 4225
DI 10.1042/BCJ20160572
PN 22
PG 21
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA EK2LR
UT WOS:000393759300009
PM 27647936
ER
PT J
AU Gueta, K
David, A
Cohen, T
Menuchin-Lasowski, Y
Nobel, H
Narkis, G
Li, LQ
Love, P
de Melo, J
Blackshaw, S
Westphal, H
Ashery-Padan, R
AF Gueta, Keren
David, Ahuvit
Cohen, Tsadok
Menuchin-Lasowski, Yotam
Nobel, Hila
Narkis, Ginat
Li, Liqi
Love, Paul
de Melo, Jimmy
Blackshaw, Seth
Westphal, Heiner
Ashery-Padan, Ruth
TI The stage-dependent roles of Ldb1 and functional redundancy with Ldb2 in
mammalian retinogenesis
SO DEVELOPMENT
LA English
DT Article
DE Isl1; Ldb1; Lhx2; Retinogenesis
ID HOMEODOMAIN TRANSCRIPTION FACTORS; PHOTORECEPTOR CELL FATE; RETINAL
GANGLION-CELLS; HOMEOBOX GENE; MOUSE RETINA; CONTROLS PROLIFERATION;
NEURAL DEVELOPMENT; PROGENITOR CELLS; EYE DEVELOPMENT; VERTEBRATE EYE
AB The Lim domain-binding proteins are key co-factor proteins that assemble with LIM domains of the LMO/LIM-HD family to form functional complexes that regulate cell proliferation and differentiation. Using conditional mutagenesis and comparative phenotypic analysis, we analyze the function of Ldb1 and Ldb2 in mouse retinal development, and demonstrate overlapping and specific functions of both proteins. Ldb1 interacts with Lhx2 in the embryonic retina and both Ldb1 and Ldb2 play a key role in maintaining the pool of retinal progenitor cells. This is accomplished by controlling the expression of the Vsx2 and Rax, and components of the Notch and Hedgehog signaling pathways. Furthermore, the Ldb1/Ldb2-mediated complex is essential for generation of early-born photoreceptors through the regulation of Rax and Crx. Finally, we demonstrate functional redundancy between Ldb1 and Ldb2. Ldb1 can fully compensate the loss of Ldb2 during all phases of retinal development, whereas Ldb2 alone is sufficient to sustain activity of Lhx2 in both early-and late-stage RPCs and in Muller glia. By contrast, loss of Ldb1 disrupts activity of the LIM domain factors in neuronal precursors. An intricate regulatory network exists that is mediated by Ldb1 and Ldb2, and promotes RPC proliferation and multipotency; it also controls specification of mammalian retina cells.
C1 [Gueta, Keren; David, Ahuvit; Menuchin-Lasowski, Yotam; Nobel, Hila; Ashery-Padan, Ruth] Tel Aviv Univ, Dept Human Mol Genet & Biochem, Sackler Fac Med, IL-69978 Tel Aviv, Israel.
[Cohen, Tsadok; Narkis, Ginat; Westphal, Heiner] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Mammalian Genes & Dev, NIH, Bethesda, MD 20892 USA.
[Li, Liqi; Love, Paul] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Genom Differentiat, NIH, Bethesda, MD 20892 USA.
[de Melo, Jimmy; Blackshaw, Seth] Johns Hopkins Univ, Solomon H Snyder Dept Neurosci, Sch Med, Baltimore, MD 21287 USA.
RP Ashery-Padan, R (reprint author), Tel Aviv Univ, Dept Human Mol Genet & Biochem, Sackler Fac Med, IL-69978 Tel Aviv, Israel.
EM ruthash@post.tau.ac.il
FU United States - Israel Binational Science Foundation [2013016]; Israel
Academy of Sciences and Humanities [228/14]; Claire and Amedee Maratier
Institute for the Study of Blindness and Visual Disorders, Tel-Aviv
University; National Institutes of Health [EY02056]
FX This work was funded by the United States - Israel Binational Science
Foundation (2013016), Israel Academy of Sciences and Humanities (228/14)
and by the Claire and Amedee Maratier Institute for the Study of
Blindness and Visual Disorders, Tel-Aviv University. The S.B. lab is
funded by the National Institutes of Health (EY02056). Deposited in PMC
for release after 12 months.
NR 75
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U1 1
U2 1
PU COMPANY OF BIOLOGISTS LTD
PI CAMBRIDGE
PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL,
CAMBS, ENGLAND
SN 0950-1991
EI 1477-9129
J9 DEVELOPMENT
JI Development
PD NOV 15
PY 2016
VL 143
IS 22
BP 4182
EP 4192
DI 10.1242/dev.129734
PG 11
WC Developmental Biology
SC Developmental Biology
GA EJ8CY
UT WOS:000393453300011
PM 27697904
ER
PT J
AU Wyss, AB
Hashibe, M
Lee, YCA
Chuang, SC
Muscat, J
Chen, C
Schwartz, SM
Smith, E
Zhang, ZF
Morgenstern, H
Wei, QY
Li, GJ
Kelsey, KT
McClean, M
Winn, DM
Schantz, S
Yu, GP
Gillison, ML
Zevallos, JP
Boffetta, P
Olshan, AF
AF Wyss, Annah B.
Hashibe, Mia
Lee, Yuan-Chin Amy
Chuang, Shu-Chun
Muscat, Joshua
Chen, Chu
Schwartz, Stephen M.
Smith, Elaine
Zhang, Zuo-Feng
Morgenstern, Hal
Wei, Qingyi
Li, Guojun
Kelsey, Karl T.
McClean, Michael
Winn, Deborah M.
Schantz, Stimson
Yu, Guo-Pei
Gillison, Maura L.
Zevallos, Jose P.
Boffetta, Paolo
Olshan, Andrew F.
TI Smokeless Tobacco Use and the Risk of Head and Neck Cancer: Pooled
Analysis of US Studies in the INHANCE Consortium
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Review
DE chewing tobacco; head and neck neoplasms; snuff; tobacco; smokeless
ID UPPER AERODIGESTIVE TRACT; SQUAMOUS-CELL CARCINOMA; ORAL-CANCER;
UNITED-STATES; EPIDEMIOLOGY CONSORTIUM; HUMAN-PAPILLOMAVIRUS;
ETIOLOGICAL FACTORS; INTERNATIONAL HEAD; PHARYNGEAL CANCER; ALCOHOL-USE
AB Previous studies on smokeless tobacco use and head and neck cancer (HNC) have found inconsistent and often imprecise estimates, with limited control for cigarette smoking. Using pooled data from 11 US case-control studies (1981-2006) of oral, pharyngeal, and laryngeal cancers (6,772 cases and 8,375 controls) in the International Head and Neck Cancer Epidemiology (INHANCE) Consortium, we applied hierarchical logistic regression to estimate odds ratios and 95% confidence intervals for ever use, frequency of use, and duration of use of snuff and chewing tobacco separately for never and ever cigarette smokers. Ever use (versus never use) of snuff was strongly associated with HNC among never cigarette smokers (odds ratio (OR) = 1.71, 95% confidence interval (CI): 1.08, 2.70), particularly for oral cavity cancers (OR = 3.01, 95% CI: 1.63, 5.55). Although ever (versus never) tobacco chewing was weakly associated with HNC among never cigarette smokers (OR = 1.20, 95% CI: 0.81, 1.77), analyses restricted to cancers of the oral cavity showed a stronger association (OR = 1.81, 95% CI: 1.04, 3.17). Few or no associations between each type of smokeless tobacco and HNC were observed among ever cigarette smokers, possibly reflecting residual confounding by smoking. Smokeless tobacco use appears to be associated with HNC, especially oral cancers, with snuff being more strongly associated than chewing tobacco.
C1 [Wyss, Annah B.] NIEHS, Epidemiol Branch, POB 12233,MD A3-05, Res Triangle Pk, NC 27599 USA.
[Wyss, Annah B.; Olshan, Andrew F.] Univ N Carolina, Dept Epidemiol, Gillings Sch Global Publ Hlth, Chapel Hill, NC USA.
[Hashibe, Mia; Lee, Yuan-Chin Amy] Univ Utah, Sch Med, Dept Family & Prevent Med, Salt Lake City, UT 84112 USA.
[Hashibe, Mia; Lee, Yuan-Chin Amy] Huntsman Canc Inst, Salt Lake City, UT USA.
[Chuang, Shu-Chun] Natl Hlth Res Inst, Inst Populat Hlth Sci, Miaoli, Taiwan.
[Muscat, Joshua] Penn State Univ, Coll Med, Dept Publ Hlth Sci, Hershey, PA USA.
[Chen, Chu; Schwartz, Stephen M.] Univ Washington, Dept Epidemiol, Sch Publ Hlth, Seattle, WA 98195 USA.
[Chen, Chu; Schwartz, Stephen M.] Fred Hutchinson Canc Res Ctr, Program Epidemiol, Div Publ Hlth Sci, Seattle, WA 98104 USA.
[Smith, Elaine] Univ Iowa, Coll Publ Hlth, Dept Epidemiol, Iowa City, IA USA.
[Zhang, Zuo-Feng] Univ Calif Los Angeles, Sch Publ Hlth, Dept Epidemiol, Los Angeles, CA 90024 USA.
[Morgenstern, Hal] Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA.
[Morgenstern, Hal] Univ Michigan, Sch Publ Hlth, Dept Environm Hlth Sci, Ann Arbor, MI 48109 USA.
[Morgenstern, Hal] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA.
[Wei, Qingyi] Duke Univ, Med Ctr, Duke Canc Ctr, Durham, NC USA.
[Li, Guojun] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Div Canc Prevent & Populat Sci, Houston, TX 77030 USA.
[Li, Guojun] Univ Texas MD Anderson Canc Ctr, Dept Head & Neck Surg, Div Surg, Houston, TX 77030 USA.
[Kelsey, Karl T.] Brown Univ, Sch Publ Hlth, Dept Epidemiol, Providence, RI 02912 USA.
[McClean, Michael] Boston Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA USA.
[Winn, Deborah M.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Schantz, Stimson; Yu, Guo-Pei] New York Eye & Ear Infirm, Dept Otolaryngol, New York, NY 10003 USA.
[Yu, Guo-Pei] Peking Univ, Med Informat Ctr, Beijing, Peoples R China.
[Gillison, Maura L.] Ohio State Univ, Dept Internal Med, Wexner Med Ctr, Columbus, OH 43210 USA.
[Zevallos, Jose P.] Univ N Carolina, Sch Med, Dept Otolaryngol Head & Neck Surg, Chapel Hill, NC USA.
[Boffetta, Paolo] Icahn Sch Med Mt Sinai, Tisch Canc Inst, New York, NY 10029 USA.
RP Wyss, AB (reprint author), NIEHS, Epidemiol Branch, POB 12233,MD A3-05, Res Triangle Pk, NC 27599 USA.
EM annah.wyss@nih.gov
FU Union for International Cancer Control International Cancer Technology
Transfer Fellowship; National Cancer Institute (NCI), National
Institutes of Health (NIH) [T32CA09330, R03CA113157]; National Institute
of Environmental Health Sciences (NIEHS), National Institutes of Health
(NIH) [T32ES007018, P30ES010126]; National Institutes of Health, NIEHS;
NIH [P01CA068384, K07CA104231, R01CA048896, R01DE012609, NIDCR
R01DE11979, NIDCR R01DE13110, NIH FIRCA TW01500, R01CA61188,
R01CA90731-01, P50CA90388]; Veterans Affairs Merit Review Funds; NIEHS
[P30ES010126]; Alper Research Program for Environmental Genomics of the
UCLA Jonsson Comprehensive Cancer Center; National Institutes of Health,
NCI; National Institute of Health [R01DA11386, R03CA77954, T32CA09142,
U01CA96134, R21ES011667, R01ES11740, R01CA131274, R01CA51845,
R01CA078609, R01CA100679, DE016631]
FX This work was supported by a Union for International Cancer Control
International Cancer Technology Transfer Fellowship; by the National
Cancer Institute (NCI) (grants T32CA09330 and R03CA113157) and the
National Institute of Environmental Health Sciences (NIEHS) (grants
T32ES007018 and P30ES010126), National Institutes of Health (NIH); and
by the Intramural Research Program of the National Institutes of Health,
NIEHS. The individual studies were funded by the following institutions
and grants-New York multicenter study (17): NIH (grants P01CA068384 and
K07CA104231); Seattle study (15, 18): NIH (grants R01CA048896 and
R01DE012609); Iowa study (19): NIH (grants NIDCR R01DE11979, NIDCR
R01DE13110, and NIH FIRCA TW01500) and the Veterans Affairs Merit Review
Funds; North Carolina studies (13, 23): NIH (grants R01CA61188 and
R01CA90731-01) and (in part) the NIEHS (grant P30ES010126); Los Angeles
study (20): NIH (grants P50CA90388, R01DA11386, R03CA77954, T32CA09142,
U01CA96134, and R21ES011667) and the Alper Research Program for
Environmental Genomics of the UCLA Jonsson Comprehensive Cancer Center;
Houston study (21): NIH (grants R01ES11740 and R01CA131274); US
multicenter study (16): Intramural Research Program of the National
Institutes of Health, NCI; New York Memorial Sloan Kettering Cancer
Center study (24): NIH (grant R01CA51845); Boston study (14): NIH
(grants R01CA078609 and R01CA100679); Baltimore study (22): NIH (grant
DE016631).
NR 53
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U1 3
U2 3
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0002-9262
EI 1476-6256
J9 AM J EPIDEMIOL
JI Am. J. Epidemiol.
PD NOV 15
PY 2016
VL 184
IS 10
BP 703
EP 716
DI 10.1093/aje/kww075
PG 14
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA EI7ZW
UT WOS:000392724700001
ER
PT J
AU Freedman, ND
AF Freedman, Neal D.
TI Invited Commentary: Smokeless Tobacco-An Important Contributor to
Cancer, but More Work Is Needed
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Editorial Material
DE case-control studies; cigarettes; head and neck neoplasms; smokeless
tobacco
ID CURRENT CIGARETTE-SMOKING; UNITED-STATES; ADULTS; TRENDS
AB In this issue of the Journal, Wyss et al. (Am J Epidemiol. 2016; 184(10): 703-716) describe the association between use of smokeless tobacco and head and neck cancer in 11 US case-control studies. Despite use by an estimated 300 million people worldwide and prior evidence for a causal association with cancer, these products remain understudied. Data are particularly needed for persons who do not use cigarettes or other smoking tobacco products. With 6,772 cancer cases and 8,375 controls, the current study is larger than previous efforts, allowing evaluation of associations among never cigarette smokers. Importantly, snuff use was positively associated with head and neck cancer, particularly for cancers of the oral cavity, whereas associations were weaker for chewing tobacco. Associations were observed among never cigarette smokers but not among ever cigarette smokers. Yet, despite the large sample size, only 44 cases and 62 controls had used snuff and only 61 cases and 96 controls had used chewing tobacco in the absence of cigarettes, precluding detailed examinations of dose response and cessation. Future studies set in high-prevalence populations with detailed assessment of lifetime use are needed to better understand the cancer risks of exclusive smokeless tobacco use and dual use of smokeless tobacco with other tobacco products, including cigarettes.
C1 [Freedman, Neal D.] NCI, Metab Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD USA.
RP Freedman, ND (reprint author), NCI, Div Canc Epidemiol & Genet, 9609 Med Ctr Way,MSC 9768, Rockville, MD 20850 USA.
EM freedmanne@mail.nih.gov
FU National Institutes of Health, National Cancer Institute, Division of
Cancer Epidemiology and Genetics
FX This work was supported by the Intramural Research Program of the
National Institutes of Health, National Cancer Institute, Division of
Cancer Epidemiology and Genetics.
NR 11
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0002-9262
EI 1476-6256
J9 AM J EPIDEMIOL
JI Am. J. Epidemiol.
PD NOV 15
PY 2016
VL 184
IS 10
BP 717
EP 719
DI 10.1093/aje/kww076
PG 3
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA EI7ZW
UT WOS:000392724700002
ER
PT J
AU Peterson, DA
Littlewort, GC
Bartlett, MS
Macerollo, A
Perlmutter, JS
Jinnah, HA
Hallett, M
Sejnowski, TJ
AF Peterson, David A.
Littlewort, Gwen C.
Bartlett, Marian S.
Macerollo, Antonella
Perlmutter, Joel S.
Jinnah, H. A.
Hallett, Mark
Sejnowski, Terrence J.
TI Objective, computerized video-based rating of blepharospasm severity
SO NEUROLOGY
LA English
DT Article
ID DEEP-BRAIN-STIMULATION; BLINK RATE; DYSTONIA; MULTICENTER; SCALES; TOXIN
AB Objective: To compare clinical rating scales of blepharospasm severity with involuntary eye closures measured automatically from patient videos with contemporary facial expression software.
Methods: We evaluated video recordings of a standardized clinical examination from 50 patients with blepharospasm in the Dystonia Coalition's Natural History and Biorepository study. Eye closures were measured on a frame-by-frame basis with software known as the Computer Expression Recognition Toolbox (CERT). The proportion of eye closure time was compared with 3 commonly used clinical rating scales: the Burke-Fahn-Marsden Dystonia Rating Scale, Global Dystonia Rating Scale, and Jankovic Rating Scale.
Results: CERT was reliably able to find the face, and its eye closure measure was correlated with all of the clinical severity ratings (Spearman rho = 0.56, 0.52, and 0.56 for the Burke-FahnMarsden Dystonia Rating Scale, Global Dystonia Rating Scale, and Jankovic Rating Scale, respectively, all p < 0.0001).
Conclusions: The results demonstrate that CERT has convergent validity with conventional clinical rating scales and can be used with video recordings to measure blepharospasm symptom severity automatically and objectively. Unlike EMG and kinematics, CERT requires only conventional video recordings and can therefore be more easily adopted for use in the clinic.
C1 [Peterson, David A.; Sejnowski, Terrence J.] Univ Calif San Diego, Computat Neurobiol Lab, Salk Inst Biol Studies, La Jolla, CA 92093 USA.
[Sejnowski, Terrence J.] Univ Calif San Diego, Howard Hughes Med Inst, Salk Inst Biol Studies, La Jolla, CA 92093 USA.
[Peterson, David A.; Littlewort, Gwen C.; Bartlett, Marian S.; Sejnowski, Terrence J.] Univ Calif San Diego, Inst Neural Computat, La Jolla, CA 92093 USA.
[Peterson, David A.; Sejnowski, Terrence J.] Univ Calif San Diego, Kavli Inst Brain & Mind, La Jolla, CA 92093 USA.
[Littlewort, Gwen C.; Bartlett, Marian S.] Univ Calif San Diego, Machine Percept Lab, La Jolla, CA 92093 USA.
[Sejnowski, Terrence J.] Univ Calif San Diego, Div Biol Sci, La Jolla, CA 92093 USA.
[Macerollo, Antonella] UCL, Inst Neurol, Natl Hosp Neurol & Neurosurg, Sobell Dept Motor Neurosci & Movement Disorders, London, England.
[Perlmutter, Joel S.] Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA.
[Perlmutter, Joel S.] Washington Univ, Sch Med, Dept Radiol, St Louis, MO 63110 USA.
[Perlmutter, Joel S.] Washington Univ, Sch Med, Dept Anat & Neurobiol, St Louis, MO 63110 USA.
[Perlmutter, Joel S.] Washington Univ, Sch Med, Program Phys Therapy, St Louis, MO USA.
[Perlmutter, Joel S.] Washington Univ, Sch Med, Program Occupat Therapy, St Louis, MO USA.
[Jinnah, H. A.] Emory Univ, Dept Neurol, Atlanta, GA 30322 USA.
[Jinnah, H. A.] Emory Univ, Dept Human Genet, Atlanta, GA 30322 USA.
[Jinnah, H. A.] Emory Univ, Dept Pediat, Atlanta, GA 30322 USA.
[Hallett, Mark] NINDS, Human Motor Control Sect, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
RP Peterson, DA (reprint author), Univ Calif San Diego, Computat Neurobiol Lab, Salk Inst Biol Studies, La Jolla, CA 92093 USA.; Peterson, DA (reprint author), Univ Calif San Diego, Inst Neural Computat, La Jolla, CA 92093 USA.; Peterson, DA (reprint author), Univ Calif San Diego, Kavli Inst Brain & Mind, La Jolla, CA 92093 USA.
EM dap@salk.edu
FU Dystonia Coalition from the Office of Rare Diseases Research at the
National Center for Advancing Translational Sciences [NS065701,
TR001456]; National Institute of Neurologic Disorders and Stroke;
Bachmann-Strauss Dystonia & Parkinson Foundation; Benign Essential
Blepharospasm Research Foundation; Kavli Institute for Brain and Mind at
UCSD; National Institute of Mental Health [NIMH 5T32-MH020002]; National
Science Foundation (Temporal Dynamics of Learning Center); National
Science Foundation (Science of Learning Center) [SMA-1041755]; National
Science Foundation (program in Mind, Machines, Motor Control)
[EFRI-1137279]; National Institute of Neurologic Disorders and Stroke
Intramural Program
FX This study was funded by the Dystonia Coalition (NS065701 and TR001456)
from the Office of Rare Diseases Research at the National Center for
Advancing Translational Sciences and the National Institute of
Neurologic Disorders and Stroke, the Bachmann-Strauss Dystonia &
Parkinson Foundation, the Benign Essential Blepharospasm Research
Foundation, the Kavli Institute for Brain and Mind at UCSD, the National
Institute of Mental Health (NIMH 5T32-MH020002), and the National
Science Foundation (the Temporal Dynamics of Learning Center, a Science
of Learning Center [SMA-1041755] and the program in Mind, Machines,
Motor Control [EFRI-1137279]). Dr. Hallett is supported by the National
Institute of Neurologic Disorders and Stroke Intramural Program. None of
the sponsors were involved in study design, collection, analysis, and
interpretation of data; writing the report; or decision to submit the
article for publication.
NR 27
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U1 1
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0028-3878
EI 1526-632X
J9 NEUROLOGY
JI Neurology
PD NOV 15
PY 2016
VL 87
IS 20
BP 2146
EP 2153
DI 10.1212/WNL.0000000000003336
PG 8
WC Clinical Neurology
SC Neurosciences & Neurology
GA EI1KM
UT WOS:000392236100016
PM 27770067
ER
PT J
AU Haass-Koffler, CL
Henry, AT
Melkus, G
Simms, JA
Naemmuddin, M
Nielsen, CK
Lasek, AW
Magill, M
Schwandt, ML
Momenan, R
Hodgkinson, CA
Bartlett, SE
Swift, RM
Bonci, A
Leggio, L
AF Haass-Koffler, C. L.
Henry, A. T.
Melkus, G.
Simms, J. A.
Naemmuddin, M.
Nielsen, C. K.
Lasek, A. W.
Magill, M.
Schwandt, M. L.
Momenan, R.
Hodgkinson, C. A.
Bartlett, S. E.
Swift, R. M.
Bonci, A.
Leggio, L.
TI Defining the role of corticotropin releasing factor binding protein in
alcohol consumption
SO TRANSLATIONAL PSYCHIATRY
LA English
DT Article
ID VENTRAL TEGMENTAL AREA; ANXIETY-RELATED BEHAVIOR; STRESS-INDUCED
RELAPSE; FACTOR-RECEPTOR; C57BL/6J MICE; ETHANOL DRINKING; BINGE
DRINKING; FACTOR CRF; RNA INTERFERENCE; COCAINE SEEKING
AB The corticotropin releasing factor (CRF) exerts its effects by acting on its receptors and on the binding protein (CRFBP), and has been implicated in alcohol use disorder (AUD). Therefore, identification of the exact contribution of each protein that mediates CRF effects is necessary to design effective therapeutic strategies for AUD. A series of in vitro/in vivo experiments across different species were performed to define the biological discrete role of CRFBP in AUD. First, to establish the CRFBP role in receptor signaling, we developed a novel chimeric cell-based assay and showed that CFRBP full length can stably be expressed on the plasma membrane. We discovered that only CRFBP(10 kD) fragment is able to potentiate CRF-intracellular Ca2+ release. We provide evidence that CRHBP gene loss increased ethanol consumption in mice. Then, we demonstrate that selective reduction of CRHBP expression in the center nucleus of the amygdala (CeA) decreases ethanol consumption in ethanol-dependent rats. CRFBP amygdalar downregulation, however, does not attenuate yohimbine-induced ethanol self-administration. This effect was associated with decreased hemodynamic brain activity in the CRFBP-downregulated CeA and increased hemodynamic activity in the caudate putamen during yohimbine administration. Finally, in alcohol-dependent patients, genetic variants related to the CRFBP(10 kD) fragment were associated with greater risk for alcoholism and anxiety, while other genetic variants were associated with reduced risk for anxiety. Taken together, our data provide evidence that CRFBP may possess both inhibitory and excitatory roles and may represent a novel pharmacological target for the treatment of AUD.
C1 [Haass-Koffler, C. L.; Leggio, L.] NIAAA, Sect Clin Psychoneuroendocrinol & Neuropsychophar, DICBR, 10 Ctr Dr 10CRC-15330,Room 1-5429, Bethesda, MD 20892 USA.
[Haass-Koffler, C. L.; Leggio, L.] NIDA, IRP, NIH, 10 Ctr Dr 10CRC-15330,Room 1-5429, Bethesda, MD 20892 USA.
[Haass-Koffler, C. L.; Swift, R. M.] Brown Univ, Dept Psychiat & Human Behav, Ctr Alcohol & Addict Studies, 121 South Main St, Providence, RI 02912 USA.
[Haass-Koffler, C. L.; Magill, M.; Leggio, L.] Brown Univ, Ctr Alcohol & Addict Studies, Dept Behav & Social Sci, Providence, RI 02912 USA.
[Henry, A. T.] Univ Chicago, Dept Psychol, 5848 S Univ Ave, Chicago, IL 60637 USA.
[Melkus, G.] Univ Ottawa, Dept Radiol, Ottawa, ON, Canada.
[Simms, J. A.; Naemmuddin, M.; Nielsen, C. K.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA.
[Lasek, A. W.] Univ Illinois, Dept Psychiat, Chicago, IL 60612 USA.
[Schwandt, M. L.] NIAAA, Off Clin Director, NIH, Bethesda, MD USA.
[Momenan, R.] NIAAA, Clin Neuroimaging Res Core, NIH, Bethesda, MD USA.
[Hodgkinson, C. A.] NIAAA, Lab Neurogenet, NIH, Rockville, MD 20852 USA.
[Bartlett, S. E.] Queensland Univ Technol, Brisbane, Qld, Australia.
[Bonci, A.] Johns Hopkins Univ, NIDA, Intramural Res Program, Baltimore, MD USA.
[Bonci, A.] Johns Hopkins Univ, Dept Neurosci, Baltimore, MD USA.
[Bonci, A.] Johns Hopkins Univ, Dept Psychiat, Baltimore, MD USA.
RP Leggio, L (reprint author), NIAAA, Sect Clin Psychoneuroendocrinol & Neuropsychophar, DICBR, 10 Ctr Dr 10CRC-15330,Room 1-5429, Bethesda, MD 20892 USA.; Leggio, L (reprint author), NIDA, IRP, NIH, 10 Ctr Dr 10CRC-15330,Room 1-5429, Bethesda, MD 20892 USA.; Haass-Koffler, CL (reprint author), Brown Univ, Dept Psychiat & Human Behav, Ctr Alcohol & Addict Studies, 121 South Main St, Providence, RI 02912 USA.
EM carolina_haass-koffler@brown.edu; lorenzo.leggio@nih.gov
FU UCSF Schools of Pharmacy and Medicine, and Strategic Opportunities
Exploratory Award; NIAAA Division of Intramural Clinical and Biological
Research; NIDA Intramural Research Program; State of California; NIH
Fast Track Award; [K01AA023867]; [T-32AA007459]
FX The authors would like to thank their funding sources: K01AA023867,
T-32AA007459, UCSF Schools of Pharmacy and Medicine, and Strategic
Opportunities Exploratory Award (CLH-K); NIAAA Division of Intramural
Clinical and Biological Research (MLS, RMS, CAH, LL) and NIDA Intramural
Research Program (AB, LL); State of California and NIH Fast Track Award
(SEB). The authors also would like to thank Dr Audrey Seasholtz,
University of Michigan, for providing the breeding pairs of the CRHBP KO
mice; the NIAAA and Clinical Center staff involved in the human data
collection at the NIH Intramural Research Program; and Ms. Karen Smith,
NIH Library for assistance.
NR 45
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U1 2
U2 2
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 2158-3188
J9 TRANSL PSYCHIAT
JI Transl. Psychiatr.
PD NOV 15
PY 2016
VL 6
DI 10.1038/tp.2016.208
PG 9
WC Psychiatry
SC Psychiatry
GA EI0AI
UT WOS:000392133200006
PM 27845775
ER
PT J
AU Guardia, CM
Farias, GG
Jia, R
Pu, J
Bonifacino, JS
AF Guardia, Carlos M.
Farias, Ginny G.
Jia, Rui
Pu, Jing
Bonifacino, Juan S.
TI BORC Functions Upstream of Kinesins 1 and 3 to Coordinate Regional
Movement of Lysosomes along Different Microtubule Tracks
SO CELL REPORTS
LA English
DT Article
ID ARF-LIKE GTPASE; RETROGRADE AXONAL-TRANSPORT; SYNAPTIC VESICLE
TRANSPORT; ALPHA-TUBULIN; POSTTRANSLATIONAL MODIFICATIONS;
CAENORHABDITIS-ELEGANS; SPATIAL-DISTRIBUTION; NONNEURONAL CELLS; MOTOR
PROTEINS; LATE ENDOSOMES
AB The multiple functions of lysosomes are critically dependent on their ability to undergo bidirectional movement along microtubules between the center and the periphery of the cell. Centrifugal and centripetal movement of lysosomes is mediated by kinesin and dynein motors, respectively. We recently described a multi-subunit complex named BORC that recruits the small GTPase Arl8 to lysosomes to promote their kinesin-dependent movement toward the cell periphery. Here, we show that BORC and Arl8 function upstream of two structurally distinct kinesin types: kinesin-1 (KIF5B) and kinesin-3 (KIF1B beta and KIF1A). Remarkably, KIF5B preferentially moves lysosomes on perinuclear tracks enriched in acetylated alpha-tubulin, whereas KIF1B beta and KIF1A drive lysosome movement on more rectilinear, peripheral tracks enriched in tyrosinated alpha-tubulin. These findings establish BORC as a master regulator of lysosome positioning through coupling to different kinesins and microtubule tracks. Common regulation by BORC enables coordinate control of lysosome movement in different regions of the cell.
C1 [Guardia, Carlos M.; Farias, Ginny G.; Jia, Rui; Pu, Jing; Bonifacino, Juan S.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cell Biol & Neurobiol Branch, NIH, Bethesda, MD 20892 USA.
RP Bonifacino, JS (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cell Biol & Neurobiol Branch, NIH, Bethesda, MD 20892 USA.
EM bonifacinoj@helix.nih.gov
OI Bonifacino, Juan S./0000-0002-5673-6370
FU Intramural Program of NICHD, NIH [ZIA HD001607]
FX We thank X. Zhu for expert technical assistance, J. Lippincott-Schwartz
for kind gifts of reagents, and T. Keren-Kaplan and D. Gershlick for
helpful discussions. This work was funded by the Intramural Program of
NICHD, NIH (ZIA HD001607).
NR 61
TC 1
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U1 1
U2 1
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 2211-1247
J9 CELL REP
JI Cell Reports
PD NOV 15
PY 2016
VL 17
IS 8
BP 1950
EP 1961
DI 10.1016/j.celrep.2016.10.062
PG 12
WC Cell Biology
SC Cell Biology
GA EG2RZ
UT WOS:000390893000005
PM 27851960
ER
PT J
AU Wada, S
Neinast, M
Jang, C
Ibrahim, YH
Lee, G
Babu, A
Li, J
Hoshino, A
Rowe, GC
Rhee, J
Martina, JA
Puertollano, R
Blenis, J
Morley, M
Baur, JA
Seale, P
Arany, Z
AF Wada, Shogo
Neinast, Michael
Jang, Cholsoon
Ibrahim, Yasir H.
Lee, Gina
Babu, Apoorva
Li, Jian
Hoshino, Atsushi
Rowe, Glenn C.
Rhee, James
Martina, Jose A.
Puertollano, Rosa
Blenis, John
Morley, Michael
Baur, Joseph A.
Seale, Patrick
Arany, Zoltan
TI The tumor suppressor FLCN mediates an alternate mTOR pathway to regulate
browning of adipose tissue
SO GENES & DEVELOPMENT
LA English
DT Article
DE adipose tissue; beige fat; mitochondria; FLCN; mTOR; TFE3
ID TRANSCRIPTION FACTOR TFE3; LYSOSOMAL BIOGENESIS; OXIDATIVE-METABOLISM;
SIGNAL INTEGRATION; RAG GTPASES; BEIGE FAT; ACTIVATION; FOLLICULIN;
AUTOPHAGY; MUSCLE
AB Noncanonical mechanistic target of rapamycin (mTOR) pathways remain poorly understood. Mutations in the tumor suppressor folliculin (FLCN) cause Birt-Hogg-Dube syndrome, a hamartomatous disease marked by mitochondria-rich kidney tumors. FLCN functionally interacts with mTOR and is expressed in most tissues, but its role in fat has not been explored. We show here that FLCN regulates adipose tissue browning via mTOR and the transcription factor TFE3. Adipose-specific deletion of FLCN relieves mTOR-dependent cytoplasmic retention of TFE3, leading to direct induction of the PGC-1 transcriptional coactivators, drivers of mitochondrial biogenesis and the browning program. Cytoplasmic retention of TFE3 by mTOR is sensitive to ambient amino acids, is independent of growth factor and tuberous sclerosis complex (TSC) signaling, is driven by RagC/D, and is separable from canonical mTOR signaling to S6K. Codeletion of TFE3 in adipose-specific FLCN knockout animals rescues adipose tissue browning, as does codeletion of PGC-1 beta. Conversely, inducible expression of PGC-1 beta in white adipose tissue is sufficient to induce beige fat gene expression in vivo. These data thus unveil a novel FLCN mTOR TFE3 PGC-1 beta pathway separate from the canonical TSC-mTOR-S6K pathway-that regulates browning of adipose tissue.
C1 [Wada, Shogo; Neinast, Michael; Jang, Cholsoon; Babu, Apoorva; Li, Jian; Hoshino, Atsushi; Morley, Michael; Baur, Joseph A.; Seale, Patrick; Arany, Zoltan] Univ Penn, Perelman Sch Med, Dept Med, Philadelphia, PA 19104 USA.
[Wada, Shogo; Neinast, Michael; Jang, Cholsoon; Babu, Apoorva; Li, Jian; Hoshino, Atsushi; Morley, Michael; Baur, Joseph A.; Seale, Patrick; Arany, Zoltan] Univ Penn, Perelman Sch Med, Cardiovasc Inst, Philadelphia, PA 19104 USA.
[Jang, Cholsoon] Princeton Univ, Chem & Integrat Genom, Princeton, NJ 08544 USA.
[Ibrahim, Yasir H.; Lee, Gina; Blenis, John] Weill Cornell Med, Meyer Canc Ctr, Dept Pharmacol, New York, NY USA.
[Rowe, Glenn C.] Univ Alabama Birmingham, Div Cardiovasc Dis, Birmingham, AL 35294 USA.
[Rhee, James] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Dept Anesthesia & Crit Care, Boston, MA 02114 USA.
[Martina, Jose A.; Puertollano, Rosa] NHLBI, Cell Biol & Physiol Ctr, NIH, Bethesda, MD 20814 USA.
RP Arany, Z (reprint author), Univ Penn, Perelman Sch Med, Dept Med, Philadelphia, PA 19104 USA.; Arany, Z (reprint author), Univ Penn, Perelman Sch Med, Cardiovasc Inst, Philadelphia, PA 19104 USA.
EM zarany@mail.med.upenn.edu
OI Rowe, Glenn/0000-0002-8195-9605
FU American Diabetes Association [1-16-PDF-117]; Toyobo Biotechnology
Foundation; University of Pennsylvania [T32 GM-07229]; LAM Foundation;
Tuberous Sclerosis Alliance; National Research Foundation of Korea;
National Institutes of Health [T32GM007592, GM51405, HL121266];
Foundation for Anesthesia Education and Research; Intramural Research
Program of the National Heart, Lung, and Blood Institute of the National
Institutes of Health; National Institute of Diabetes and Digestive and
Kidney Diseases [DK098656, DK107667]; National Institute on Aging
[AG043483]; National Heart, Lung, and Blood Institute [HL094499]
FX We thank Bridget Gosis for technical support and critical discussion;
Dr. Antonio Davila Jr. for expert advice; Dr. Eleftheria Maratos-Flier
in Beth Israel Deaconess Medical Center/Harvard Medical School for CLAMS
and DEXA analyses; Dr. Rexford Ahima, Dr. Frederick Anokye-Danso, and
the Diabetes Research Center (DRC) Mouse Phenotyping Core at the
University of Pennsylvania for in vivo respiration assay (P30-DK19525);
Andrea Stout and Jasmine Zhao from the Cell and Developmental Biology
Microscopy Core at the University of Pennsylvania for confocal
microscopy imaging; Raymond Meade from the Electron Microscopy Resource
laboratory at the Perelman School of Medicine, University of
Pennsylvania, for TEM imaging; and Lan Cheng from the Histology and Gene
Expression Core at the University of Pennsylvania Cardiovascular
Institute for histology sample processing. S.W. is supported by an
American Diabetes Association Postdoctoral Fellowship Award
(1-16-PDF-117) and was supported by the Toyobo Biotechnology Foundation.
M.N. is supported by a University of Pennsylvania Cell and Molecular
Biology training grant (T32 GM-07229). G.L. is supported by the LAM
Foundation, the Tuberous Sclerosis Alliance, and the National Research
Foundation of Korea. J.R. was supported by grants from the National
Institutes of Health [T32GM007592] and a Mentored Research Training
Grant from the Foundation for Anesthesia Education and Research. J.A.M.
and R.P. were supported by the Intramural Research Program of the
National Heart, Lung, and Blood Institute of the National Institutes of
Health. J.B. is supported by the National Institutes of Health (GM51405
and HL121266). J.A.B. is supported by the National Institute of Diabetes
and Digestive and Kidney Diseases (DK098656) and National Institute on
Aging (AG043483). Z.A. is supported by the National Institute of
Diabetes and Digestive and Kidney Diseases (DK107667) and National
Heart, Lung, and Blood Institute (HL094499). S.W. designed and conducted
the experiments, analyzed/interpreted the data, and wrote the
manuscript. C.J. and M.N. conducted experiments and analyzed data.
Y.H.I., G.L., and J.A.B conducted the in vitro kinase assay and gave
intellectual input on mTOR signaling. A.B. and M.M. performed
bioinformatics analysis on RNA-seq data. J.L. and A.H. generated
critical reagents. J.A.M. and R.P. generated the phospho-TFE3
(Ser320)-specific antibody and gave intellectual input on TFE3 biology.
G.C.R., J.R., JAB., and P.S. assisted in critical discussion and study
design. Z.A. designed the study, interpreted the data, and wrote the
manuscript.
NR 47
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U1 1
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PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
PI COLD SPRING HARBOR
PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA
SN 0890-9369
EI 1549-5477
J9 GENE DEV
JI Genes Dev.
PD NOV 15
PY 2016
VL 30
IS 22
BP 2551
EP 2564
DI 10.1101/gad.287953.116
PG 14
WC Cell Biology; Developmental Biology; Genetics & Heredity
SC Cell Biology; Developmental Biology; Genetics & Heredity
GA EF8XQ
UT WOS:000390615700008
PM 27913603
ER
PT J
AU Si, CP
Zhang, RH
Wu, TS
Lu, GM
Hu, Y
Zhang, H
Xu, FH
Wei, P
Chen, K
Tang, H
Yeretssian, G
Xiong, HB
AF Si, Chuanping
Zhang, Ruihua
Wu, Tianshu
Lu, Geming
Hu, Yuan
Zhang, Hui
Xu, Feihong
Wei, Peter
Chen, Kang
Tang, Hua
Yeretssian, Garabet
Xiong, Huabao
TI Dendritic cell-derived nitric oxide inhibits the differentiation of
effector dendritic cells
SO ONCOTARGET
LA English
DT Article
DE dendritic cell; iNOS
ID KAPPA-B ACTIVATION; NLRP3 INFLAMMASOME; TYROSINE NITRATION; MECHANISM;
SYNTHASES; IMMUNITY; DISEASE
AB Dendritic cells (DCs) play a pivotal role in the development of effective immune defense while avoiding detrimental inflammation and autoimmunity by regulating the balance of adaptive immunity and immune tolerance. However, the mechanisms that govern the effector and regulatory functions of DCs are incompletely understood. Here, we show that DC-derived nitric oxide (NO) controls the balance of effector and regulatory DC differentiation. Mice deficient in the NO-producing enzyme inducible nitric oxide synthase (iNOS) harbored increased effector DCs that produced interleukin-12, tumor necrosis factor (TNF) and IL-6 but normal numbers of regulatory DCs that expressed IL-10 and programmed cell death-1 (PD-1). Furthermore, an iNOS-specific inhibitor selectively enhanced effector DC differentiation, mimicking the effect of iNOS deficiency in mice. Conversely, an NO donor significantly suppressed effector DC development. Furthermore, iNOS-/-DCs supported enhanced T cell activation and proliferation. Finally iNOS-/-mice infected with the enteric pathogen Citrobacter rodentium suffered more severe intestinal inflammation with concomitant expansion of effector DCs in colon and spleen. Collectively, our results demonstrate that DC-derived iNOS restrains effector DC development, and offer the basis of therapeutic targeting of iNOS in DCs to treat autoimmune and inflammatory diseases.
C1 [Si, Chuanping; Zhang, Hui; Xiong, Huabao] Jining Med Coll, Inst Immunol & Mol Med, Rizhao 272067, Shandong, Peoples R China.
[Zhang, Ruihua; Wu, Tianshu; Lu, Geming; Hu, Yuan; Xu, Feihong; Wei, Peter; Yeretssian, Garabet; Xiong, Huabao] Icahn Sch Med Mt Sinai, Inst Immunol, Dept Med, New York, NY 10029 USA.
[Chen, Kang] Wayne State Univ, Dept Obstet & Gynecol, Perinatol Res Branch,NIH, Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Detroit, MI 48201 USA.
[Tang, Hua] Taishan Med Univ, Inst Immunol, Tai An 271000, Shandong, Peoples R China.
RP Xiong, HB (reprint author), Jining Med Coll, Inst Immunol & Mol Med, Rizhao 272067, Shandong, Peoples R China.; Zhang, RH; Xiong, HB (reprint author), Icahn Sch Med Mt Sinai, Inst Immunol, Dept Med, New York, NY 10029 USA.
EM ruihua.zhang@mssm.edu; huabao.xiong@mssm.edu
FU US National Institutes of Health [P01DK072201, R56AI091871, R01AI104688]
FX This work was supported by grants from the US National Institutes of
Health (P01DK072201, R56AI091871 and R01AI104688 to H.X.).
NR 32
TC 0
Z9 0
U1 0
U2 0
PU IMPACT JOURNALS LLC
PI ALBANY
PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA
SN 1949-2553
J9 ONCOTARGET
JI Oncotarget
PD NOV 15
PY 2016
VL 7
IS 46
BP 74834
EP 74845
DI 10.18632/oncotarget.11361
PG 12
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA EE5GF
UT WOS:000389632800032
PM 27556858
ER
PT J
AU Chen, T
Xu, J
Liu, GQ
Liu, H
Chen, MJ
Qin, YF
Wu, W
Xia, YK
Ji, CB
Guo, XR
Wen, J
Wang, XR
AF Chen, Ting
Xu, Juan
Liu, Guangquan
Liu, Heng
Chen, Minjian
Qin, Yufeng
Wu, Wei
Xia, Yankai
Ji, Chenbo
Guo, Xirong
Wen, Juan
Wang, Xinru
TI Genetic variants in PTPRD and risk of gestational diabetes mellitus
SO ONCOTARGET
LA English
DT Article
DE PTPRD; polymorphism; gestational diabetes mellitus; susceptibility
ID GENOME-WIDE ASSOCIATION; PROTEIN-TYROSINE-PHOSPHATASE; WOMEN; LAR;
METAANALYSIS; SIGNALS; DELTA; LEADS; SIGMA; MICE
AB Genome-wide association studies (GWASs) showed that two single nucleotide polymorphisms (SNPs) (rs17584499 and rs649891) in the protein tyrosine phosphatase receptor type D (PTPRD) were associated with type 2 diabetes (T2D). We sought to determine the influence of the PTPRD variants on the gestational diabetes mellitus (GDM) risk. In this research, two SNPs in PTPRD reported in T2D GWASs and six PTPRD expression-related SNPs were genotyped in 964 GDM cases and 1,021 controls using the Sequenom platform. Logistic regression analyses in additive models showed consistently significant associations of PTPRD rs10511544 A>C, rs10756026 T>A and rs10809070 C>G with a decreased risk of GDM [ adjusted OR (95% CI) = 0.83 (0.72-0.97) for rs10511544; adjusted OR (95% CI) = 0.81 (0.70-0.94) for rs10756026; adjusted OR (95% CI) = 0.78 (0.65-0.92) for rs10809070]. Furthermore, the risk of GDM was significantly decreased with an increasing number of variant alleles of the three SNPs in a dose-dependent manner (P-trend = 0.008). Moreover, the haplotype containing variant alleles of the three SNPs were significantly associated with a decreased risk of GDM [ adjusted OR (95% CI) = 0.77 (0.64-0.92), P = 0.005], when compared with the most frequent haplotype. However, there were no significant associations for the SNPs reported in the T2D GWASs. Altogether, these findings indicate that the variants of rs10511544, rs10756026 and rs10809070 in PTPRD may contribute to a decreased susceptibility to GDM. Further validation in different ethnic backgrounds and biological function analyses are needed.
C1 [Chen, Ting; Chen, Minjian; Wu, Wei; Xia, Yankai; Wang, Xinru] Nanjing Med Univ, Inst Toxicol, State Key Lab Reprod Med, Nanjing 211166, Jiangsu, Peoples R China.
[Chen, Ting; Chen, Minjian; Wu, Wei; Xia, Yankai; Wang, Xinru] Nanjing Med Univ, Sch Publ Hlth, Minist Educ, Key Lab Modern Toxicol, Nanjing 211166, Jiangsu, Peoples R China.
[Chen, Ting; Xu, Juan; Liu, Guangquan; Liu, Heng; Ji, Chenbo; Guo, Xirong; Wen, Juan] Nanjing Med Univ, Nanjing Matern & Child Hlth Care Hosp, Nanjing Matern & Child Hlth Care Inst, Nanjing 210004, Jiangsu, Peoples R China.
[Xu, Juan] Nanjing Med Univ, Nanjing Matern & Child Hlth Care Hosp, Dept Obstet & Gynecol, Nanjing 210004, Jiangsu, Peoples R China.
[Qin, Yufeng] Natl Inst Environm Hlth Sci, Epigenet & Stem Cell Biol Lab, Res Triangle Pk, NC 27709 USA.
[Ji, Chenbo; Guo, Xirong; Wen, Juan] Nanjing Med Univ, Nanjing Matern & Child Hlth Care Hosp, Dept Children Hlth Care, Nanjing 210004, Jiangsu, Peoples R China.
RP Wang, XR (reprint author), Nanjing Med Univ, Inst Toxicol, State Key Lab Reprod Med, Nanjing 211166, Jiangsu, Peoples R China.; Wang, XR (reprint author), Nanjing Med Univ, Sch Publ Hlth, Minist Educ, Key Lab Modern Toxicol, Nanjing 211166, Jiangsu, Peoples R China.; Wen, J (reprint author), Nanjing Med Univ, Nanjing Matern & Child Hlth Care Hosp, Nanjing Matern & Child Hlth Care Inst, Nanjing 210004, Jiangsu, Peoples R China.; Wen, J (reprint author), Nanjing Med Univ, Nanjing Matern & Child Hlth Care Hosp, Dept Children Hlth Care, Nanjing 210004, Jiangsu, Peoples R China.
EM wenj2010@gmail.com; xrwang@njmu.edu.cn
FU National Natural Science Foundation of China [81401232, 81600685];
Nanjing Medical Science and technique Development Foundation [QRX11222];
Natural Science Foundation of Jiangsu Province [BK20160141]; Science and
Technology Development Fund of the Nanjing Medical University
[2015NJMUZD062]
FX This work was supported in part by the National Natural Science
Foundation of China (81401232, 81600685), Nanjing Medical Science and
technique Development Foundation (QRX11222), the Natural Science
Foundation of Jiangsu Province (BK20160141), and the Science and
Technology Development Fund of the Nanjing Medical University
(2015NJMUZD062).
NR 22
TC 0
Z9 0
U1 0
U2 0
PU IMPACT JOURNALS LLC
PI ALBANY
PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA
SN 1949-2553
J9 ONCOTARGET
JI Oncotarget
PD NOV 15
PY 2016
VL 7
IS 46
BP 76101
EP 76107
DI 10.18632/oncotarget.12599
PG 7
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA EE5GF
UT WOS:000389632800129
PM 27738328
ER
PT J
AU Galanternik, MV
Lush, ME
Piotrowski, T
AF Galanternik, Marina Venero
Lush, Mark E.
Piotrowski, Tatjana
TI Glypican4 modulates lateral line collective cell migration non
cell-autonomously
SO DEVELOPMENTAL BIOLOGY
LA English
DT Article
DE Primordium; Wnt/beta-catenin; FGF; Proteoglycans; Lateral line;
Morphogenesis; Laminin gamma 1; Sulf1; Heparinase III; extl3/ext2;
boxer; dackel
ID HEPARAN-SULFATE PROTEOGLYCANS; SLOW MUSCLE PRECURSORS; WNT SIGNALING
PATHWAYS; CONVERGENT EXTENSION; WNT/BETA-CATENIN; TISSUE MIGRATION;
GASTRULATION MOVEMENTS; ZEBRAFISH MYOTOME; HSPG SYNTHESIS; CHEMOKINE
AB Collective cell migration is an essential process during embryonic development and diseases such as cancer, and still much remains to be learned about how cell intrinsic and environmental cues are coordinated to guide cells to their targets. The migration-dependent development of the zebrafish sensory lateral line proves to be an excellent model to study how proteoglycans control collective cell migration in a vertebrate. Proteoglycans are extracellular matrix glycoproteins essential for the control of several signaling pathways including Wnt/beta-catenin, Fgf, BMP and Hh. In the lateral line primordium the modified sugar chains on proteoglycans are important regulators of cell polarity, ligand distribution and Fgf signaling. At least five proteoglycans show distinct expression patterns in the primordium; however, their individual functions have not been studied. Here, we describe the function of glypican4 during zebrafish lateral line development. glypican4 is expressed in neuromasts, interneuromast cells and muscle cells underlying the lateral line. knypek(fr6)/glypican4 mutants show severe primordium migration defects and the primordium often U-turns and migrates back toward the head. Our analysis shows that Glypican4 regulates the feedback loop between Wnt/beta-catenin/Fgf signaling in the primordium redundantly with other Heparan Sulfate Proteoglycans. In addition, the primordium migration defect is caused non-cell autonomously by the loss of cxcl12a-expressing muscle precursors along the myoseptum via downregulation of Hh. Our results show that glypican4 has distinct functions in primordium cells and cells in the environment and that both of these functions are essential for collective cell migration. (C) 2016 Published by Elsevier Inc.
C1 [Galanternik, Marina Venero; Piotrowski, Tatjana] Stowers Inst Med Res, 1000 East 50th St, Kansas City, MO 64110 USA.
[Galanternik, Marina Venero; Lush, Mark E.; Piotrowski, Tatjana] Univ Utah, Dept Neurobiol & Anat, Salt Lake City, UT 84132 USA.
[Galanternik, Marina Venero] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD 20892 USA.
RP Piotrowski, T (reprint author), Stowers Inst Med Res, 1000 East 50th St, Kansas City, MO 64110 USA.
EM pio@stowers.org
FU American Cancer Research Scholar grant [RSG CCG 114528]
FX We thank Dr. Solnica-Krezel for sharing the
knypekfr6/glypican4 mutants, Dr. Hirsinger for providing the
engrailed1a, 1b, 2a and patched2 plasmids and Ana Gabriel for cloning
the id1 probe. We are grateful to Joaquin Navajas Acedo and all
Piotrowski Lab members for valuable discussions and suggestions. We
thank the University of Utah CZAR and Stowers Aquatics Facility for
excellent fish husbandry. We also thank Dr. Hua Li from the Stowers
Institute Bioinformatics Core for help with statistical analysis and
Mark Miller for help with graphical design. This work was supported by
an American Cancer Research Scholar grant (RSG CCG 114528) to T.P. and
institutional support from the Stowers Institute for Medical Research.
NR 71
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U1 1
U2 1
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0012-1606
EI 1095-564X
J9 DEV BIOL
JI Dev. Biol.
PD NOV 15
PY 2016
VL 419
IS 2
BP 321
EP 335
DI 10.1016/j.ydbio.2016.09.002
PG 15
WC Developmental Biology
SC Developmental Biology
GA EE4IV
UT WOS:000389566400011
ER
PT J
AU Hart, GT
Akkaya, M
Chida, AS
Wei, CW
Jenks, SA
Tipton, C
He, CF
Wendel, BS
Skinner, J
Arora, G
Kayentao, K
Ongoiba, A
Doumbo, O
Traore, B
Narum, DL
Jiang, N
Crompton, PD
Sanz, I
Pierce, SK
AF Hart, Geoffrey T.
Akkaya, Munir
Chida, Asiya S.
Wei, Chungwen
Jenks, Scott A.
Tipton, Christopher
He, Chenfeng
Wendel, Ben S.
Skinner, Jeff
Arora, Gunjan
Kayentao, Kassoum
Ongoiba, Aissata
Doumbo, Ogobara
Traore, Boubacar
Narum, David L.
Jiang, Ning
Crompton, Peter D.
Sanz, Ignacio
Pierce, Susan K.
TI The Regulation of Inherently Autoreactive VH4-34-Expressing B Cells in
Individuals Living in a Malaria-Endemic Area of West Africa
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; PLASMODIUM-FALCIPARUM; NEUTRALIZING
ANTIBODIES; AUTOIMMUNE-DISEASE; ACQUIRED-IMMUNITY; HIV-1 ANTIBODIES; 9G4
IDIOTOPE; GENE SEGMENT; INFECTION; RESPONSES
AB Plasmodium falciparum malaria is a deadly infectious disease in which Abs play a critical role in naturally acquired immunity. However, the specificity and nature of Abs elicited in response to malaria are only partially understood. Autoreactivity and polyreactivity are common features of Ab responses in several infections and were suggested to contribute to effective pathogen-specific Ab responses. In this article, we report on the regulation of B cells expressing the inherently autoreactive VH4-34 H chain (identified by the 9G4 mAb) and 9G4(+) plasma IgG in adults and children living in a P. falciparum malaria-endemic area in West Africa. The frequency of 9G4(+) peripheral blood CD19(+) B cells was similar in United States adults and African adults and children; however, more 9G4(+) B cells appeared in classical and atypical memory B cell compartments in African children and adults compared with United States adults. The levels of 9G4(+) IgG increased following acute febrile malaria but did not increase with age as humoral immunity is acquired or correlate with protection from acute disease. This was the case, even though a portion of 9G4(+) B cells acquired phenotypes of atypical and classical memory B cells and 9G4(+) IgG contained equivalent numbers of somatic hypermutations compared with all other VHs, a characteristic of secondary Ab repertoire diversification in response to Ag stimulation. Determining the origin and function of 9G4(+) B cells and 9G4(+) IgG in malaria may contribute to a better understanding of the varied roles of autoreactivity in infectious diseases.
C1 [Hart, Geoffrey T.; Akkaya, Munir; Skinner, Jeff; Arora, Gunjan; Crompton, Peter D.; Pierce, Susan K.] NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA.
[Chida, Asiya S.; Wei, Chungwen; Jenks, Scott A.; Sanz, Ignacio] Emory Univ, Div Rheumatol, Dept Med, Lowance Ctr Human Immunol, Atlanta, GA 30322 USA.
[Tipton, Christopher] Adapt Biotechnol Seattle, Seattle, WA 98102 USA.
[He, Chenfeng; Jiang, Ning] Univ Texas Austin, Cockrell Sch Engn, Dept Biomed Engn, Austin, TX 78712 USA.
[Wendel, Ben S.] Univ Texas Austin, McKetta Dept Chem Engn, Cockrell Sch Engn, Austin, TX 78712 USA.
[Kayentao, Kassoum; Ongoiba, Aissata; Doumbo, Ogobara; Traore, Boubacar] Univ Sci Tech & Technol Bamako, Int Ctr Excellence Res, Dept Epidemiol Parasit Dis, Malaria Res & Training Ctr, Bamako, Mali.
[Narum, David L.] NIAID, Lab Malaria Immunol & Vaccinol, NIH, Rockville, MD 20852 USA.
RP Pierce, SK (reprint author), NIAID, NIH, Room 200B,MSC 8180,12441 Parklawn Dr, Rockville, MD 20852 USA.
EM spierce@nih.gov
OI AKKAYA, Munir/0000-0002-9949-9424
FU Intramural Research Program of the National Institute of Allergy and
Infectious Diseases, National Institutes of Health; Autoimmunity Center
of Excellence - National Institutes of Health [5R37AI049660, U19
AI110483]
FX This work was supported by the Intramural Research Program of the
National Institute of Allergy and Infectious Diseases, National
Institutes of Health and by Grants 5R37AI049660 and U19 AI110483 from
the Autoimmunity Center of Excellence awarded by the National Institutes
of Health (to I.S.).
NR 51
TC 0
Z9 0
U1 1
U2 1
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
EI 1550-6606
J9 J IMMUNOL
JI J. Immunol.
PD NOV 15
PY 2016
VL 197
IS 10
BP 3841
EP 3849
DI 10.4049/jimmunol.1600491
PG 9
WC Immunology
SC Immunology
GA EE5GW
UT WOS:000389634600010
PM 27798155
ER
PT J
AU Riteau, N
Radtke, AJ
Shenderov, K
Mittereder, L
Oland, SD
Hieny, S
Jankovic, D
Sher, A
AF Riteau, Nicolas
Radtke, Andrea J.
Shenderov, Kevin
Mittereder, Lara
Oland, Sandra D.
Hieny, Sara
Jankovic, Dragana
Sher, Alan
TI Water-in-Oil-Only Adjuvants Selectively Promote T Follicular Helper Cell
Polarization through a Type I IFN and IL-6-Dependent Pathway
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID TRANSCRIPTION FACTOR; ANTIBODY-RESPONSES; DIFFERENTIATION; BCL6;
T-HELPER-1; SIGNALS; INFLAMMASOME; MICROBIOTA; INDUCTION; ANTIGEN
AB T follicular helper (Tfh) cells are a subset of CD4(+) T lymphocytes that promote the development of humoral immunity. Although the triggers required for the differentiation of the other major Th subsets are well defined, those responsible for Tfh cell responses are still poorly understood. We determined that mice immunized with peptide or protein Ags emulsified in IFA or related water-in-oil adjuvants develop a highly polarized response in which the majority of the Ag-specific CD4(+) T cells are germinal center-homing CXCR5(+)Bcl6(+) Tfh cells. Despite the absence of exogenous microbial pathogen-associated molecular patterns, the Tfh cell responses observed were dependent, in part, on MyD88. Importantly, in addition to IL-6, T cell-intrinsic type I IFN signaling is required for optimal Tfh cell polarization. These findings suggest that water-in-oil adjuvants promote Tfh cell-dominated responses by triggering endogenous alarm signals that, in turn, induce type I IFN-dependent differentiation pathway functioning in T cells.
C1 [Riteau, Nicolas; Shenderov, Kevin; Mittereder, Lara; Oland, Sandra D.; Hieny, Sara; Jankovic, Dragana; Sher, Alan] NIAID, Immunobiol Sect, Parasit Dis Lab, NIH, Bldg 50,50 South Dr, Bethesda, MD 20892 USA.
[Radtke, Andrea J.] NIAID, Lymphocyte Biol Sect, Lab Syst Biol, NIH, Bethesda, MD 20892 USA.
RP Sher, A (reprint author), NIAID, Immunobiol Sect, Parasit Dis Lab, NIH, Bldg 50,50 South Dr, Bethesda, MD 20892 USA.
EM asher@niaid.nih.gov
OI Sher, Alan/0000-0001-7053-2895
FU National Institute of Allergy and Infectious Diseases, National
Institutes of Health
FX This work was supported by the Intramural Research and the Intramural
Vaccine Adjuvant Programs of the National Institute of Allergy and
Infectious Diseases, National Institutes of Health.
NR 32
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U1 0
U2 0
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
EI 1550-6606
J9 J IMMUNOL
JI J. Immunol.
PD NOV 15
PY 2016
VL 197
IS 10
BP 3884
EP 3893
DI 10.4049/jimmunol.1600883
PG 10
WC Immunology
SC Immunology
GA EE5GW
UT WOS:000389634600014
PM 27798160
ER
PT J
AU Chen, YJ
Wilson, R
O'Dell, S
Guenaga, J
Feng, Y
Tran, K
Chiang, CI
Arendt, HE
DeStefano, J
Mascola, JR
Wyatt, RT
Li, YX
AF Chen, Yajing
Wilson, Richard
O'Dell, Sijy
Guenaga, Javier
Feng, Yu
Tran, Karen
Chiang, Chi-I
Arendt, Heather E.
DeStefano, Joanne
Mascola, John R.
Wyatt, Richard T.
Li, Yuxing
TI An HIV-1 Env-Antibody Complex Focuses Antibody Responses to Conserved
Neutralizing Epitopes
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID CD4 BINDING-SITE; ENVELOPE GLYCOPROTEIN GP120; VIRUS TYPE-1 GP120;
MONOCLONAL-ANTIBODY; CD4-BINDING SITE; STRUCTURAL BASIS; CROSS-LINKING;
NONHUMAN-PRIMATES; MASS-SPECTROMETRY; IMMUNOGEN DESIGN
AB Elicitation of broadly neutralizing Ab (bNAb) responses to the conserved elements of the HIV-1 envelope glycoproteins (Env), including the primary receptor CD4 binding site (CD4bs), is a major focus of vaccine development yet to be accomplished. However, a large number of CD4bs-directed bNAbs have been isolated from HIV-1-infected individuals. Comparison of the routes of binding used by the CD4bs-directed bNAbs from patients and the vaccine-elicited CD4bs-directed mAbs indicates that the latter fail to neutralize primary virus isolates because they approach the Env spike with a vertical angle and contact the specific surface residues occluded in the native spike, including the bridging sheet on gp120. To preferentially expose the CD4bs and direct the immune response away from the bridging sheet, resulting in an altered angle of approach, we engineered an immunogen consisting of gp120 core in complex with the prototypic CD4-induced Ab, 17b. This mAb directly contacts the bridging sheet but not the CD4bs. The complex was further stabilized by chemical crosslinking to prevent dissociation. Rabbits immunized with the crosslinked complex displayed earlier affinity maturation, achieving tier 1 virus neutralization compared with animals immunized with gp120 core alone. Immunization with the crosslinked complex induced transient Ab responses with binding specificity similar to the CD4bs-directed bNAbs. mAbs derived from complex-immunized rabbits displayed footprints on gp120 more distal from the bridging sheet as compared with previous vaccine-elicited CD4bs Abs, indicating that Env-Ab complexes effectively dampen immune responses to undesired immunodominant bridging sheet determinants.
C1 [Chen, Yajing; Wyatt, Richard T.; Li, Yuxing] Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA.
[Wilson, Richard; Guenaga, Javier; Feng, Yu; Tran, Karen; Wyatt, Richard T.; Li, Yuxing] Scripps Res Inst, Int AIDS Vaccine Initiat Neutralizing Antibody Ct, La Jolla, CA 92037 USA.
[O'Dell, Sijy] NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Chiang, Chi-I; Li, Yuxing] Univ Maryland, Inst Biosci & Biotechnol Res, 9600 Gudelsky Dr, Rockville, MD 20850 USA.
[Arendt, Heather E.; DeStefano, Joanne] Int AIDS Vaccine Initiat, Brooklyn, NY 11226 USA.
[Wyatt, Richard T.] Scripps Ctr HIV Immunogen Discovery, La Jolla, CA 92037 USA.
RP Li, YX (reprint author), Univ Maryland, Inst Biosci & Biotechnol Res, 9600 Gudelsky Dr, Rockville, MD 20850 USA.
EM liy@ibbr.umd.edu
FU National Institutes of Health/National Institute of Allergy and
Infectious Diseases [R01AI102766]; National Institute of Allergy and
Infectious Diseases Development [P30AI36214, P01 AI104722, UM1
AI100663]; Intramural Research Program of the Vaccine Research Center,
National Institute of Allergy and Infectious Diseases, National
Institutes of Health; International AIDS Vaccine Initiative; United
States Agency for International Development; Ministry of Foreign Affairs
of the Netherlands; Bill and Melinda Gates Foundation
FX This work was supported by National Institutes of Health/National
Institute of Allergy and Infectious Diseases Grant R01AI102766 (to
Y.L.), National Institute of Allergy and Infectious Diseases Development
Grant P30AI36214 to the Center for AIDS Research, University of
California, San Diego (to Y.L.), Grants P01 AI104722 (to R.T.W. and
Y.L.) and UM1 AI100663 (to R.T.W.), as well as funding from the
Intramural Research Program of the Vaccine Research Center, National
Institute of Allergy and Infectious Diseases, National Institutes of
Health (to J.R.M.). This work was also supported in part by the
International AIDS Vaccine Initiative (to R.T.W.) with the generous
support of United States Agency for International Development, the
Ministry of Foreign Affairs of the Netherlands, and by the Bill and
Melinda Gates Foundation; a full list of International AIDS Vaccine
Initiative donors is available at http://www.iavi.org.
NR 71
TC 0
Z9 0
U1 2
U2 2
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
EI 1550-6606
J9 J IMMUNOL
JI J. Immunol.
PD NOV 15
PY 2016
VL 197
IS 10
BP 3982
EP 3998
DI 10.4049/jimmunol.1601134
PG 17
WC Immunology
SC Immunology
GA EE5GW
UT WOS:000389634600023
PM 27815444
ER
PT J
AU Hu, X
Valentin, A
Dayton, F
Kulkarni, V
Alicea, C
Rosati, M
Chowdhury, B
Gautam, R
Broderick, KE
Sardesai, NY
Martin, MA
Mullins, JI
Pavlakis, GN
Felber, BK
AF Hu, Xintao
Valentin, Antonio
Dayton, Frances
Kulkarni, Viraj
Alicea, Candido
Rosati, Margherita
Chowdhury, Bhabadeb
Gautam, Rajeev
Broderick, Kate E.
Sardesai, Niranjan Y.
Martin, Malcolm A.
Mullins, James I.
Pavlakis, George N.
Felber, Barbara K.
TI DNA Prime-Boost Vaccine Regimen To Increase Breadth, Magnitude, and
Cytotoxicity of the Cellular Immune Responses to Subdominant Gag
Epitopes of Simian Immunodeficiency Virus and HIV
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID T-LYMPHOCYTE RESPONSES; CONSERVED REGIONS; RHESUS-MONKEYS; VIRAL LOADS;
MACAQUES; CHALLENGE; INFECTION; COVERAGE; TYPE-1; CELLS
AB HIV sequence diversity and the propensity of eliciting immunodominant responses targeting variable regions of the HIV proteome are hurdles in the development of an effective AIDS vaccine. An HIV-derived conserved element (CE) p24(gag) plasmid DNA (pDNA) vaccine is able to redirect immunodominant responses to otherwise subdominant and often more vulnerable viral targets. By homology to the HIV immunogen, seven CE were identified in SIV p27(Gag). Analysis of 31 rhesus macaques vaccinated with full-length SIV gag pDNA showed inefficient induction (58% response rate) of cellular responses targeting these CE. In contrast, all 14 macaques immunized with SIV p27CE pDNA developed robust T cell responses recognizing CE. Vaccination with p27CE pDNA was also critical for the efficient induction and increased the frequency of Ag-specific T cells with cytotoxic potential (granzyme B+CD107a(+)) targeting subdominant CE epitopes, compared with the responses elicited by the p57(gag) pDNA vaccine. Following p27CE pDNA priming, two booster regimens, gag pDNA or codelivery of p27CE+gag pDNA, significantly increased the levels of CE-specific T cells. However, the CE+gag pDNA booster vaccination elicited significantly broader CE epitope recognition, and thus, a more profound alteration of the immunodominance hierarchy. Vaccination with HIV molecules showed that CE+gag pDNA booster regimen further expanded the breadth of HIV CE responses. Hence, SIV/HIV vaccine regimens comprising CE pDNA prime and CE+gag pDNA booster vaccination significantly increased cytotoxic T cell responses to subdominant highly conserved Gag epitopes and maximized response breadth.
C1 [Hu, Xintao; Dayton, Frances; Kulkarni, Viraj; Alicea, Candido; Felber, Barbara K.] NCI, Human Retrovirus Pathogenesis Sect, Vaccine Branch, Ctr Canc Res, Frederick, MD 21702 USA.
[Valentin, Antonio; Rosati, Margherita; Chowdhury, Bhabadeb; Pavlakis, George N.] NCI, Human Retrovirus Sect, Vaccine Branch, Ctr Canc Res, Frederick, MD 21702 USA.
[Gautam, Rajeev; Martin, Malcolm A.] NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA.
[Broderick, Kate E.; Sardesai, Niranjan Y.] Inovio Pharmaceut, Plymouth Meeting, PA 19462 USA.
[Mullins, James I.] Univ Washington, Dept Microbiol, Seattle, WA 98195 USA.
[Mullins, James I.] Univ Washington, Dept Med, Seattle, WA 98195 USA.
[Mullins, James I.] Univ Washington, Dept Global Hlth, Seattle, WA 98195 USA.
[Mullins, James I.] Univ Washington, Dept Lab Med, Seattle, WA 98195 USA.
RP Pavlakis, GN; Felber, BK (reprint author), NCI, Vaccine Branch, Ctr Canc Res, POB B,Bldg 535,Room 206, Frederick, MD 21702 USA.
EM george.pavlakis@nih.gov; barbara.felber@nih.gov
RI bebarta, vikhyat/K-3476-2015
FU Intramural Research Program of the National Cancer Institute; National
Institute of Allergy and Infectious Disease, National Institutes of
Health (NIAID/NIH) [P01 AI057005]; University of Washington Centers for
AIDS Research Molecular Profiling Computational Biology Core (NIH) [P30
AI27757]; NIAID/NIH Division of AIDS [HHSN272200800063C]
FX This work was supported by the Intramural Research Program of the
National Cancer Institute (to G.N.P. and B.K.F.), National Institute of
Allergy and Infectious Disease, National Institutes of Health
(NIAID/NIH), Grant P01 AI057005 (to M.A.M.), and the University of
Washington Centers for AIDS Research Molecular Profiling Computational
Biology Core (NIH Grant P30 AI27757; to J.I.M.). This work also was
supported in part by the NIAID/NIH Division of AIDS under HIV Vaccine
Design and Development Teams Contract HHSN272200800063C (to N.Y.S.).
NR 60
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U1 3
U2 3
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
EI 1550-6606
J9 J IMMUNOL
JI J. Immunol.
PD NOV 15
PY 2016
VL 197
IS 10
BP 3999
EP 4013
DI 10.4049/jimmunol.1600697
PG 15
WC Immunology
SC Immunology
GA EE5GW
UT WOS:000389634600024
PM 27733554
ER
PT J
AU Bjornstad, ON
Viboud, C
AF Bjornstad, Ottar N.
Viboud, Cecile
TI Timing and periodicity of influenza epidemics
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Editorial Material
ID TRANSMISSION; SEASONALITY; HUMIDITY; DYNAMICS; PATTERNS
C1 [Bjornstad, Ottar N.] Penn State Univ, Dept Entomol, University Pk, PA 16802 USA.
[Bjornstad, Ottar N.] Penn State Univ, Dept Biol, University Pk, PA 16802 USA.
[Viboud, Cecile] NIH, Div Int Epidemiol & Populat Studies, Fogarty Int Ctr, Bethesda, MD 20892 USA.
RP Bjornstad, ON (reprint author), Penn State Univ, Dept Entomol, University Pk, PA 16802 USA.; Bjornstad, ON (reprint author), Penn State Univ, Dept Biol, University Pk, PA 16802 USA.
EM onb1@psu.edu
NR 20
TC 1
Z9 1
U1 4
U2 4
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 NOV 15
PY 2016
VL 113
IS 46
BP 12899
EP 12901
DI 10.1073/pnas.1616052113
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA ED6MQ
UT WOS:000388970100031
PM 27810955
ER
PT J
AU Rogozin, IB
Belinky, F
Pavlenko, V
Shabalina, SA
Kristensen, DM
Koonin, EV
AF Rogozin, Igor B.
Belinky, Frida
Pavlenko, Vladimir
Shabalina, Svetlana A.
Kristensen, David M.
Koonin, Eugene V.
TI Evolutionary switches between two serine codon sets are driven by
selection
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE tandem nucleotide substitutions; serine codon sets; purifying selection;
positive selection; homoplasy
ID LONG-BRANCH ATTRACTION; MULTIPLE MUTATIONS; PROTEIN EVOLUTION;
DNA-POLYMERASE; SACCHAROMYCES-CEREVISIAE; PHYLOGENETIC ANALYSIS;
MOLECULAR EVOLUTION; GENES; HYPERMUTABILITY; SUBSTITUTIONS
AB Serine is the only amino acid that is encoded by two disjoint codon sets so that a tandem substitution of two nucleotides is required to switch between the two sets. Previously published evidence suggests that, for the most evolutionarily conserved serines, the codon set switch occurs by simultaneous substitution of two nucleotides. Here we report a genome-wide reconstruction of the evolution of serine codons in triplets of closely related species from diverse prokaryotes and eukaryotes. The results indicate that the great majority of codon set switches proceed by two consecutive nucleotide substitutions, via a threonine or cysteine intermediate, and are driven by selection. These findings imply a strong pressure of purifying selection in protein evolution, which in the case of serine codon set switches occurs via an initial deleterious substitution quickly followed by a second, compensatory substitution. The result is frequent reversal of amino acid replacements and, at short evolutionary distances, pervasive homoplasy.
C1 [Rogozin, Igor B.; Belinky, Frida; Pavlenko, Vladimir; Shabalina, Svetlana A.; Koonin, Eugene V.] Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA.
[Kristensen, David M.] Univ Iowa, Biomed Engn Dept, Iowa City, IA 52242 USA.
RP Koonin, EV (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA.
EM koonin@ncbi.nlm.nih.gov
FU Intramural Research Program of the National Library of Medicine at the
National Institutes of Health
FX We thank Michael Galperin, Kira Makarova, David Landsman, Joshua Cherry,
and Yuri Wolf for helpful discussions and Olga Batyreva for statistical
advice. This research was supported in part by the Intramural Research
Program of the National Library of Medicine at the National Institutes
of Health.
NR 47
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U1 6
U2 6
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD NOV 15
PY 2016
VL 113
IS 46
BP 13109
EP 13113
DI 10.1073/pnas.1615832113
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA ED6MQ
UT WOS:000388970100068
PM 27799560
ER
PT J
AU Xie, ZQ
Babiceanu, M
Kumar, S
Jia, YM
Qin, FJ
Barr, FG
Li, H
AF Xie, Zhongqiu
Babiceanu, Mihaela
Kumar, Shailesh
Jia, Yuemeng
Qin, Fujun
Barr, Frederic G.
Li, Hui
TI Fusion transcriptome profiling provides insights into alveolar
rhabdomyosarcoma
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE rhabdomyosarcoma; gene fusion; chimeric RNA; myogenesis; PAX3-FOXO1
ID CELL LUNG-CANCER; RNA-SEQ DATA; TARGET GENES; STEM-CELLS; EXPRESSION;
IDENTIFICATION; TRANSLOCATION; ONCOPROTEIN; INDIVIDUALS; PROTEINS
AB Gene fusions and fusion products were thought to be unique features of neoplasia. However, more and more studies have identified fusion RNAs in normal physiology. Through RNA sequencing of 27 human noncancer tissues, a large number of fusion RNAs were found. By analyzing fusion transcriptome, we observed close clusterings between samples of same or similar tissues, supporting the feasibility of using fusion RNA profiling to reveal connections between biological samples. To put the concept into use, we selected alveolar rhabdomyosarcoma (ARMS), a myogenic pediatric cancer whose exact cell of origin is not clear. PAX3-FOXO1 (paired box gene 3 fused with forkhead box O1) fusion RNA, which is considered a hallmark of ARMS, was recently found during normal muscle cell differentiation. We performed and analyzed RNA sequencing from various time points during myogenesis and uncovered many chimeric fusion RNAs. Interestingly, we found that the fusion RNA profile of RH30, an ARMS cell line, is most similar to the myogenesis time point when PAX3-FOXO1 is expressed. In contrast, full transcriptome clustering analysis failed to uncover this connection. Strikingly, all of the 18 chimeric RNAs in RH30 cells could be detected at the samemyogenic time point(s). In addition, the seven chimeric RNAs that follow the exact transient expression pattern as PAX3-FOXO1 are specific to rhabdomyosarcoma cells. Further testing with clinical samples also confirmed their specificity to rhabdomyosarcoma. These results provide further support for the link between at least some ARMSs and the PAX3-FOXO1-expressing myogenic cells and demonstrate that fusion RNA profiling can be used to investigate the etiology of fusion-gene-associated cancers.
C1 [Xie, Zhongqiu; Babiceanu, Mihaela; Kumar, Shailesh; Jia, Yuemeng; Qin, Fujun; Li, Hui] Univ Virginia, Dept Pathol, Charlottesville, VA 22908 USA.
[Barr, Frederic G.] NCI, Pathol Lab, Bethesda, MD 20892 USA.
[Li, Hui] Univ Virginia, Ctr Canc, Charlottesville, VA 22908 USA.
RP Li, H (reprint author), Univ Virginia, Dept Pathol, Charlottesville, VA 22908 USA.; Li, H (reprint author), Univ Virginia, Ctr Canc, Charlottesville, VA 22908 USA.
EM hl9r@virginia.edu
RI Qin, Fujun/I-8629-2016
FU St. Baldrick's V Scholar grant; intramural program of the National
Cancer Institute
FX We thank Drs. Carola Ponzetto and Riccardo Taulli for providing
pBABE-PAX3-FOXO1 construct; Dr. Bishwanath Chatterjee for technical
assistance; Drs. Dutta, Liang, Triche, Biegel, Mandahl, Ladanyi,
Epstein, Shapiro, and Tronick for providing us the tumor cell lines; and
Loryn Facemire and Fuming Yi for their technical support. This work is
supported by St. Baldrick's V Scholar grant. F.G.B. is supported by the
intramural program of the National Cancer Institute.
NR 41
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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 NOV 15
PY 2016
VL 113
IS 46
BP 13126
EP 13131
DI 10.1073/pnas.1612734113
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA ED6MQ
UT WOS:000388970100071
PM 27799565
ER
PT J
AU Rui, LX
Drennan, AC
Ceribelli, M
Zhu, F
Wright, GW
Huang, DW
Xiao, WM
Li, YG
Grindle, KM
Lu, L
Hodson, DJ
Shaffer, AL
Zhao, H
Xu, WH
Yang, YD
Staudt, LM
AF Rui, Lixin
Drennan, Amanda C.
Ceribelli, Michele
Zhu, Fen
Wright, George W.
Huang, Da Wei
Xiao, Wenming
Li, Yangguang
Grindle, Kreg M.
Lu, Li
Hodson, Daniel J.
Shaffer, Arthur L.
Zhao, Hong
Xu, Weihong
Yang, Yandan
Staudt, Louis M.
TI Epigenetic gene regulation by Janus kinase 1 in diffuse large B-cell
lymphoma
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE JAK1; epigenetics; histone modification; lymphoma; oncogene
ID NF-KAPPA-B; STAT3; CANCER; MECHANISMS; DISEASE; TRANSCRIPTION;
DEREGULATION; SIGNATURES; MUTATIONS; CHROMATIN
AB Janus kinases (JAKs) classically signal by activating STAT transcription factors but can also regulate gene expression by epigenetically phosphorylating histone H3 on tyrosine 41 (H3Y41-P). In diffuse large B-cell lymphomas (DLBCLs), JAK signaling is a feature of the activated B-cell (ABC) subtype and is triggered by autocrine production of IL-6 and IL-10. Whether this signaling involves STAT activation, epigenetic modification of chromatin, or both mechanisms is unknown. Here we use genetic and pharmacological inhibition to show that JAK1 signaling sustains the survival of ABC DLBCL cells. Whereas STAT3 contributed to the survival of ABC DLBCL cell lines, forced STAT3 activity could not protect these cells from death following JAK1 inhibition, suggesting epigenetic JAK1 action. JAK1 regulated the expression of nearly 3,000 genes in ABC DLBCL cells, and the chromatin surrounding many of these genes was modified by H3Y41-P marks that were diminished by JAK1 inhibition. These JAK1 epigenetic target genes encode important regulators of ABC DLBCL proliferation and survival, including IRF4, MYD88, and MYC. A small molecule JAK1 inhibitor cooperated with the BTK inhibitor ibrutinib in reducing IRF4 levels and acted synergistically to kill ABC DLBCL cells, suggesting that this combination should be evaluated in clinical trials.
C1 [Rui, Lixin; Ceribelli, Michele; Huang, Da Wei; Hodson, Daniel J.; Shaffer, Arthur L.; Zhao, Hong; Xu, Weihong; Yang, Yandan; Staudt, Louis M.] NCI, Lymphoid Malignancies Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Rui, Lixin; Drennan, Amanda C.; Zhu, Fen; Li, Yangguang; Grindle, Kreg M.; Lu, Li] Univ Wisconsin, Sch Med & Publ Hlth, Dept Med, Madison, WI 53705 USA.
[Rui, Lixin; Drennan, Amanda C.; Zhu, Fen; Li, Yangguang; Grindle, Kreg M.; Lu, Li] Univ Wisconsin, Sch Med & Publ Hlth, Carbone Canc Ctr, Madison, WI 53705 USA.
[Wright, George W.] NCI, Biometr Res Branch, DCTD, NIH, Bethesda, MD 20892 USA.
[Xiao, Wenming] US FDA, Div Bioinformat & Biostat, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA.
RP Rui, LX; Staudt, LM (reprint author), NCI, Lymphoid Malignancies Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.; Rui, LX (reprint author), Univ Wisconsin, Sch Med & Publ Hlth, Dept Med, Madison, WI 53705 USA.; Rui, LX (reprint author), Univ Wisconsin, Sch Med & Publ Hlth, Carbone Canc Ctr, Madison, WI 53705 USA.
EM lrui@medicine.wisc.edu; lstaudt@mail.nih.gov
FU Intramural Research Program of the NIH National Cancer Institute;
University of Wisconsin-Madison (UW-Madison) start-up funds; KL2 Scholar
Awards [UL1TR0000427, KL2TR000428]; National Cancer Institute [1R01
CA187299]; UW-Madison T32 Hematology Training Award [T32 HL07899]
FX This research was supported by the Intramural Research Program of the
NIH National Cancer Institute, the University of Wisconsin-Madison
(UW-Madison) start-up funds, KL2 Scholar Awards UL1TR0000427 and
KL2TR000428, the National Cancer Institute Grant 1R01 CA187299 (to
L.R.), and the UW-Madison T32 Hematology Training Award T32 HL07899 (to
A.C.D.).
NR 40
TC 1
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U1 4
U2 4
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 NOV 15
PY 2016
VL 113
IS 46
BP E7260
EP E7267
DI 10.1073/pnas.1610970113
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA ED6MQ
UT WOS:000388970100016
PM 27799566
ER
PT J
AU Fujikado, N
Mann, AO
Bansal, K
Romito, KR
Ferre, EMN
Rosenzweig, SD
Lionakis, MS
Benoist, C
Mathis, D
AF Fujikado, Noriyuki
Mann, Alexander O.
Bansal, Kushagra
Romito, Kimberly R.
Ferre, Elise M. N.
Rosenzweig, Sergio D.
Lionakis, Michail S.
Benoist, Christophe
Mathis, Diane
TI Aire Inhibits the Generation of a Perinatal Population of
Interleukin-17A-Producing gamma delta T Cells to Promote Immunologic
Tolerance
SO IMMUNITY
LA English
DT Article
ID CHRONIC MUCOCUTANEOUS CANDIDIASIS; THYMIC EPITHELIAL-CELLS; ECTODERMAL
DYSTROPHY; INTERFERON-GAMMA; IL-17 PRODUCTION; GENE-EXPRESSION;
SELF-TOLERANCE; TCR REPERTOIRE; RNA-SEQ; SELECTION
AB Aire's primary mechanism of action is to regulate transcription of a battery of genes in medullary thymic epithelial cells ( mTECs) and, consequently, negative selection of effector T cells and positive selection of regulatory T cells. We found that Aire-deficient mice had expanded thymic and peripheral populations of perinatally generated IL-17A(+)V gamma 6(+) V delta 1(+)T cells, considered to be "early responders'' to tissue stress and drivers of inflammatory reactions. Aire-dependent control of Ii7 expression in mTECs regulated the size of thymic IL-17A(+)V gamma 6(+) V delta 1(+)T compartments. In mice lacking Aire and gd T cells, certain tissues typically targeted in the `` Aire-less'' disease, notably the retina, were only minimally infiltrated. IL-17A(+)V gamma 6(+) V delta 1(+)T cells were present in the retina of wild-type mice and expanded very early in Aire-deficientmice. A putatively parallel population of IL-17A(+)V gamma 6(+) V delta 1(+)T cells was increased in humans lacking Aire. Thus, Aire exerts multi-faceted autoimmune control that extends to a population of innate-like T cells.
C1 [Fujikado, Noriyuki; Mann, Alexander O.; Bansal, Kushagra; Benoist, Christophe; Mathis, Diane] Harvard Med Sch, Dept Microbiol & Immunobiol, Div Immunol, Boston, MA 02115 USA.
[Romito, Kimberly R.; Rosenzweig, Sergio D.] NIH, Dept Lab Med, NIH Clin Ctr, Bethesda, MD 20892 USA.
[Ferre, Elise M. N.; Lionakis, Michail S.] NIAID, Fungal Pathogenesis Unit, Lab Clin Infect Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Fujikado, Noriyuki] Eli Lilly Japan KK, Minato Ku, Tokyo 1070052, Japan.
RP Benoist, C; Mathis, D (reprint author), Harvard Med Sch, Dept Microbiol & Immunobiol, Div Immunol, Boston, MA 02115 USA.
EM cb@hms.harvard.edu; dm@hms.harvard.edu
FU NIH [R01 DK060027, T32 AI118692]; NIH NIAID Division of Intramural
Research; Japan Society for the Promotion of Science; Uehara Memorial
Foundation; American Diabetes Association [7-12-MN-51]
FX We would like to thank Drs. V. Kuchroo, P. Love, and M. Anderson for
mice; Drs. R. Tigelaar and J. Lewis for the 17D1 hybridoma; K. Hattori
for expert assistance with mice; Dr. A. Ortiz-Lopez for histological
scoring; the NIH Tetramer Core Facility for provision of tetramer
reagents; Dr. N. Asinovski for hybridoma culture; and Drs. H. Yoshida
and S. Yang for insightful discussions. This work was supported by NIH
grant R01 DK060027 to D.M. and in part by the NIH NIAID Division of
Intramural Research. N.F. received fellowships from the Japan Society
for the Promotion of Science and the Uehara Memorial Foundation, K.B.
received a fellowship from the American Diabetes Association
(7-12-MN-51), and A.O.M. received a fellowship from the NIH (T32
AI118692).
NR 65
TC 0
Z9 0
U1 4
U2 4
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1074-7613
EI 1097-4180
J9 IMMUNITY
JI Immunity
PD NOV 15
PY 2016
VL 45
IS 5
BP 999
EP 1012
DI 10.1016/j.immuni.2016.10.023
PG 14
WC Immunology
SC Immunology
GA EE3FP
UT WOS:000389473500012
PM 27851927
ER
PT J
AU Yu, X
Cai, BW
Wang, MJ
Tan, P
Ding, XL
Wu, J
Li, J
Li, QT
Liu, PH
Xing, CS
Wang, HY
Su, XZ
Wang, RF
AF Yu, Xiao
Cai, Baowei
Wang, Mingjun
Tan, Peng
Ding, Xilai
Wu, Jian
Li, Jian
Li, Qingtian
Liu, Pinghua
Xing, Changsheng
Wang, Helen Y.
Su, Xin-zhuan
Wang, Rong-Fu
TI Cross-Regulation of Two Type I Interferon Signaling Pathways in
Plasmacytoid Dendritic Cells Controls Anti-malaria Immunity and Host
Mortality
SO IMMUNITY
LA English
DT Article
ID PERSISTENT LCMV INFECTION; CEREBRAL MALARIA; RESPONSES; DNA;
RECOGNITION; AUTOIMMUNITY; PARASITES; BLOCKADE; INSIGHTS; MICE
AB Type I interferon (IFN) is critical for controlling pathogen infection; however, its regulatory mechanisms in plasmacytoid cells (pDCs) still remain unclear. Here, we have shown that nucleic acid sensors cGAS-, STING-, MDA5-, MAVS-, or transcription factor IRF3-deficient mice produced high amounts of type I IFN-alpha and IFN-beta (IFN-a/b) in the serum and were resistant to lethal plasmodium yoelii YM infection. Robust IFN-alpha/beta production was abolished when gene encoding nucleic acid sensor TLR7, signaling adaptor MyD88, or transcription factor IRF7 was ablated or pDCs were depleted. Further, we identified SOCS1 as a key negative regulator to inhibit MyD88-dependent type I IFN signaling in pDCs. Finally, we have demonstrated that pDCs, cDCs, and macrophages were required for generating IFN-alpha/beta-induced subsequent protective immunity. Thus, our findings have identified a critical regulatory mechanism of type I IFN signaling in pDCs and stage-specific function of immune cells in generating potent immunity against lethal YM infection.
C1 [Yu, Xiao] Sun Yat Sen Univ, Sch Life Sci, Guangzhou 510275, Guangdong, Peoples R China.
[Wang, Mingjun] Sun Yat Sen Univ, Zhongshan Sch Med, Guangzhou 510275, Guangdong, Peoples R China.
[Yu, Xiao; Cai, Baowei; Wang, Mingjun; Tan, Peng; Ding, Xilai; Li, Qingtian; Liu, Pinghua; Xing, Changsheng; Wang, Helen Y.; Wang, Rong-Fu] Houston Methodist Res Inst, Ctr Inflammat & Epigenet, Houston, TX 77030 USA.
[Cai, Baowei; Li, Jian; Su, Xin-zhuan] Xiamen Univ, Sch Life Sci, Innovat Ctr Cell Biol, State Key Lab Cellular Stress Biol, Xiamen 361005, Fujian, Peoples R China.
[Wu, Jian; Su, Xin-zhuan] NIAID, Lab Malaria & Vector Res, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Wang, Rong-Fu] Cornell Univ, Dept Microbiol & Immunol, Weill Cornell Med, New York, NY 10065 USA.
[Tan, Peng; Wang, Rong-Fu] Texas A&M Univ, Coll Med, Inst Biosci & Technol, Houston, TX 77030 USA.
RP Wang, RF (reprint author), Houston Methodist Res Inst, Ctr Inflammat & Epigenet, Houston, TX 77030 USA.; Su, XZ (reprint author), Xiamen Univ, Sch Life Sci, Innovat Ctr Cell Biol, State Key Lab Cellular Stress Biol, Xiamen 361005, Fujian, Peoples R China.; Su, XZ (reprint author), NIAID, Lab Malaria & Vector Res, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.; Wang, RF (reprint author), Cornell Univ, Dept Microbiol & Immunol, Weill Cornell Med, New York, NY 10065 USA.; Wang, RF (reprint author), Texas A&M Univ, Coll Med, Inst Biosci & Technol, Houston, TX 77030 USA.
EM xsu@niaid.nih.gov; rwang3@houstonmethodist.org
OI Su, Xinzhuan/0000-0003-3246-3248
FU China Scholar Council; NCI, NIH [R01CA101795, DA030338]; NIDA, NIH
[R01CA101795, DA030338]; Division of Intramural Research at the National
Institute of Allergy and Infectious Diseases (NIAID)
FX We thank Marco Colonna (Washington University School of Medicine) for
providing Tlr9-/- mice, Richard A. Flavell (Yale University)
for Tlr7-/- mice, Kate Fitzgerald (University of
Massachusetts Medical School) and Tadatsugo Taniguchi (The University of
Tokyo) for Irf3-/-:Irf7-/- mice, Michael Gale
(University of Washington) and Wenxin Wu (University of Oklahoma Health
Science Center) for Ddx58-/- mice, and Skip Virgin
(Washington University at St. Louis) for Mb21d1-/- mice, Bo
Ning for art drawing, and Jana S. Burchfield for editing the manuscript.
X.Y. and B.C. were partially supported by the China Scholar Council.
This work was supported, in part, by grants (R01CA101795 and DA030338)
from the NCI and NIDA, NIH to R.-F.W. and by the Division of Intramural
Research at the National Institute of Allergy and Infectious Diseases
(NIAID).
NR 37
TC 2
Z9 2
U1 9
U2 9
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1074-7613
EI 1097-4180
J9 IMMUNITY
JI Immunity
PD NOV 15
PY 2016
VL 45
IS 5
BP 1093
EP 1107
DI 10.1016/j.immuni.2016.10.001
PG 15
WC Immunology
SC Immunology
GA EE3FP
UT WOS:000389473500019
PM 27793594
ER
PT J
AU Huang, JH
Kang, BH
Ishida, E
Zhou, TQ
Griesman, T
Sheng, ZZ
Wu, F
Doria-Rose, NA
Zhang, BS
McKee, K
O'Dell, S
Chuang, GY
Druz, A
Georgiev, IS
Schramm, CA
Zheng, AQ
Joyce, MG
Asokan, M
Ransier, A
Darko, S
Migueles, SA
Bailer, RT
Louder, MK
Alam, SM
Parks, R
Kelsoe, G
Von Holle, T
Haynes, BF
Douek, DC
Hirsch, V
Seaman, MS
Shapiro, L
Mascola, JR
Kwong, PD
Connors, M
AF Huang, Jinghe
Kang, Byong H.
Ishida, Elise
Zhou, Tongqing
Griesman, Trevor
Sheng, Zizhang
Wu, Fan
Doria-Rose, Nicole A.
Zhang, Baoshan
McKee, Krisha
O'Dell, Sijy
Chuang, Gwo-Yu
Druz, Aliaksandr
Georgiev, Ivelin S.
Schramm, Chaim A.
Zheng, Anqi
Joyce, M. Gordon
Asokan, Mangaiarkarasi
Ransier, Amy
Darko, Sam
Migueles, Stephen A.
Bailer, Robert T.
Louder, Mark K.
Alam, S. Munir
Parks, Robert
Kelsoe, Garnett
Von Holle, Tarra
Haynes, Barton F.
Douek, Daniel C.
Hirsch, Vanessa
Seaman, Michael S.
Shapiro, Lawrence
Mascola, John R.
Kwong, Peter D.
Connors, Mark
TI Identification of a CD4-Binding-Site Antibody to HIV that Evolved
Near-Pan Neutralization Breadth
SO IMMUNITY
LA English
DT Article
ID TYPE-1 INFECTION; ESCAPE; MATURATION; ENVELOPE; EVOLUTION; GLYCOPROTEIN;
PATTERNS; POTENCY; GLYCANS; LINEAGE
AB Detailed studies of the broadly neutralizing antibodies (bNAbs) that underlie the best available examples of the humoral immune response to HIV are providing important information for the development of therapies and prophylaxis for HIV-1 infection. Here, we report a CD4-binding site (CD4bs) antibody, named N6, that potently neutralized 98% of HIV-1 isolates, including 16 of 20 that were resistant to other members of its class. N6 evolved a mode of recognition such that its binding was not impacted by the loss of individual contacts across the immunoglobulin heavy chain. In addition, structural analysis revealed that the orientation of N6 permitted it to avoid steric clashes with glycans, which is a common mechanism of resistance. Thus, an HIV-1-specific bNAb can achieve potent, near-pan neutralization of HIV-1, making it an attractive candidate for use in therapy and prophylaxis.
C1 [Huang, Jinghe; Kang, Byong H.; Ishida, Elise; Griesman, Trevor; Migueles, Stephen A.; Connors, Mark] NIAID, HIV Specif Immun Sect, Immunoregulat Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Zhou, Tongqing; Doria-Rose, Nicole A.; Zhang, Baoshan; McKee, Krisha; O'Dell, Sijy; Chuang, Gwo-Yu; Druz, Aliaksandr; Zheng, Anqi; Joyce, M. Gordon; Asokan, Mangaiarkarasi; Ransier, Amy; Darko, Sam; Bailer, Robert T.; Louder, Mark K.; Douek, Daniel C.; Shapiro, Lawrence; Mascola, John R.; Kwong, Peter D.] NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Wu, Fan; Hirsch, Vanessa] NIAID, Mol Microbiol Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Sheng, Zizhang; Schramm, Chaim A.; Shapiro, Lawrence] Columbia Univ, Dept Biochem & Mol Biophys, New York, NY 10032 USA.
[Georgiev, Ivelin S.] Vanderbilt Univ, Med Ctr, Dept Pathol Microbiol & Immunol, Nashville, TN 37232 USA.
[Alam, S. Munir; Parks, Robert; Kelsoe, Garnett; Von Holle, Tarra; Haynes, Barton F.] Duke Univ, Duke Human Vaccine Inst, Durham, NC 27710 USA.
[Seaman, Michael S.] Harvard Med Sch, Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
RP Connors, M (reprint author), NIAID, HIV Specif Immun Sect, Immunoregulat Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM mconnors@nih.gov
FU Intramural Research Program and the Vaccine Research Center, National
Institute of Allergy and Infectious Diseases (NIAID), NIH; US Department
of Energy, Basic Energy Sciences, Office of Science [W-31-109-Eng-38]
FX We thank the members of the Vaccine Research Center for discussions of
the manuscript. We thank Lynn Morris for arranging the testing of N6
against an extended clade C pseudovirus panel. We thank J. Baalwa, D.
Ellenberger, F. Gao, B. Hahn, K. Hong, J. Kim, F. McCutchan, D.
Montefiori, L. Morris, J. Overbaugh, E. Sanders-Buell, G. Shaw, R.
Swanstrom, M. Thomson, S. Tovanabutra, C. Williamson, and L. Zhang for
contributing the HIV-1 envelope plasmids used in our neutralization
panel. Support for this work was provided by the Intramural Research
Program and the Vaccine Research Center, National Institute of Allergy
and Infectious Diseases (NIAID), NIH. Use of sector 22 (Southeast Region
Collaborative Access team) at the Advanced Photon Source was supported
by the US Department of Energy, Basic Energy Sciences, Office of Science
under contract number W-31-109-Eng-38.
NR 37
TC 3
Z9 3
U1 4
U2 4
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1074-7613
EI 1097-4180
J9 IMMUNITY
JI Immunity
PD NOV 15
PY 2016
VL 45
IS 5
BP 1108
EP 1121
DI 10.1016/j.immuni.2016.10.027
PG 14
WC Immunology
SC Immunology
GA EE3FP
UT WOS:000389473500020
PM 27851912
ER
PT J
AU Lu, Y
Biancotto, A
Cheung, F
Remmers, E
Shah, N
McCoy, JP
Tsang, JS
AF Lu, Yong
Biancotto, Angelique
Cheung, Foo
Remmers, Elaine
Shah, Naisha
McCoy, J. Philip
Tsang, John S.
TI Systematic Analysis of Cell-to-Cell Expression Variation of T
Lymphocytes in a Human Cohort Identifies Aging and Genetic Associations
SO IMMUNITY
LA English
DT Article
ID FLUCTUATING ENVIRONMENTS; FLOW-CYTOMETRY; IMMUNE; HETEROGENEITY;
DISEASE; ARCHITECTURE; VARIABILITY; RESPONSES; SUBSETS; NOISE
AB Cell-to-cell expression variation (CEV) is a prevalent feature of even well-defined cell populations, but its functions, particularly at the organismal level, are not well understood. Using single-cell data obtained via high-dimensional flow cytometry of T cells as a model, we introduce an analysis framework for quantifying CEV in primary cell populations and studying its functional associations in human cohorts. Analyses of 840 CEV phenotypes spanning multiple baseline measurements of 14 proteins in 28 T cell subpopulations suggest that the quantitative extent of CEV can exhibit substantial subject-to-subject differences and yet remain stable within healthy individuals over months. We linked CEV to age and disease-associated genetic polymorphisms, thus implicating CEV as a biomarker of aging and disease susceptibility and suggesting that it might play an important role in health and disease. Our dataset, interactive figures, and software for computing CEV with flow cytometry data provide a resource for exploring CEV functions.
C1 [Lu, Yong; Shah, Naisha; Tsang, John S.] NIAID, Syst Genom & Bioinformat Unit, Lab Syst Biol, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Biancotto, Angelique; Cheung, Foo; McCoy, J. Philip; Tsang, John S.] NIH, Trans NIH Ctr Human Immunol Autoimmun & Inflammat, Bethesda, MD 20892 USA.
[Remmers, Elaine] NHGRI, NIH, Bethesda, MD 20892 USA.
[McCoy, J. Philip] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA.
RP Tsang, JS (reprint author), NIAID, Syst Genom & Bioinformat Unit, Lab Syst Biol, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.; Tsang, JS (reprint author), NIH, Trans NIH Ctr Human Immunol Autoimmun & Inflammat, Bethesda, MD 20892 USA.
EM john.tsang@nih.gov
FU intramural program of the NIAID; NIH
FX We thank Adrian Wiestner for providing healthy samples for
age-association validation; Candace Liu for help with figures and
software testing; Pamela Schwartzberg, Nicolas van Panhuys, and Ronald
Germain for comments on the manuscript; and members of the J.S.T. lab
and the Trans-NIH Center for Human Immunology (CHI) for discussions.
This work was funded by the intramural program of the NIAID and of NIH
institutes supporting the CHI.
NR 57
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U1 6
U2 6
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1074-7613
EI 1097-4180
J9 IMMUNITY
JI Immunity
PD NOV 15
PY 2016
VL 45
IS 5
BP 1162
EP 1175
DI 10.1016/j.immuni.2016.10.025
PG 14
WC Immunology
SC Immunology
GA EE3FP
UT WOS:000389473500024
PM 27851916
ER
PT J
AU Crank, MC
Wilson, EMP
Novik, L
Enama, ME
Hendel, CS
Gu, WJ
Nason, MC
Bailer, RT
Nabel, GJ
McDermott, AB
Mascola, JR
Koup, RA
Ledgerwood, JE
Graham, BS
AF Crank, Michelle C.
Wilson, Eleanor M. P.
Novik, Laura
Enama, Mary E.
Hendel, Cynthia S.
Gu, Wenjuan
Nason, Martha C.
Bailer, Robert T.
Nabel, Gary J.
McDermott, Adrian B.
Mascola, John R.
Koup, Richard A.
Ledgerwood, Julie E.
Graham, Barney S.
CA VRC012 Study Team
TI Safety and Immunogenicity of a rAd35-EnvA Prototype HIV-1 Vaccine in
Combination with rAd5-EnvA in Healthy Adults (VRC 012)
SO PLOS ONE
LA English
DT Article
ID T-CELL RESPONSES; TEST-OF-CONCEPT; DNA CANDIDATE VACCINE;
IMMUNE-RESPONSES; ADENOVIRUS VECTORS; 1ST-IN-HUMAN EVALUATION;
NONHUMAN-PRIMATES; PROSTATE-CANCER; PHASE-1 SAFETY; EFFICACY TRIAL
AB Background
VRC 012 was a Phase I study of a prototype recombinant adenoviral-vector serotype-35 (rAd35) HIV vaccine, the precursor to two recently published clinical trials, HVTN 077 and 083. On the basis of prior evaluation of multiclade rAd5 HIV vaccines, Envelope A (EnvA) was selected as the standard antigen for a series of prototype HIV vaccines to compare various vaccine platforms. In addition, prior studies of rAd5-vectored vaccines suggested preexisting human immunity may be a confounding factor in vaccine efficacy. rAd35 is less seroprevalent across human populations and was chosen for testing alone and in combination with a rAd5-EnvA vaccine in the present two-part phase I study.
Methods
First, five subjects each received a single injection of 10(9), 10(10), or 10(11) particle units (PU) of rAd35-EnvA in an open-label, dose-escalation study. Next, 20 Ad5/Ad35-seronegative subjects were randomized to blinded, heterologous prime-boost schedules combining rAd5-EnvA and rAd35-EnvA with a three month interval. rAd35-EnvA was given at 10(10) or 10(11) PU to ten subjects each; all rAd5-EnvA injections were 10(10) PU. EnvA-specific immunogenicity was assessed four weeks post-injection. Solicited reactogenicity and clinical safety were followed after each injection.
Results
Vaccinations were well tolerated at all dosages. Antibody responses measured by ELISA were detected at 4 weeks in 30% and 50% of subjects after single doses of 10(10) or 10(11) PU rAd35, respectively, and in 89% after a single rAd5-EnvA 10(10) PU injection. EnvA-specific IFN-Upsilon ELISpot responses were detected at four weeks in 0%, 70%, and 50% of subjects after the respective rAd35-EnvA dosages compared to 89% of subjects after rAd5. T cell responses were higher after a single rAd5-EnvA 10(10) PU injection than after a single rAd35-EnvA 10(10) PU injection, and humoral responses were low after a single dose of either vector. Of those completing the vaccine schedule, 100% of rAd5-EnvA recipients and 90% of rAd35-EnvA recipients had both T cell and humoral responses after boosting with the heterologous vector. ELISpot response magnitude was similar in both regimens and comparable to a single dose of rAd5. A trend toward more robust CD8 T cell responses using rAd5-EnvA prime and rAd35-EnvA boost was observed. Humoral response magnitude was also similar after either heterologous regimen, but was several fold higher than after a single dose of rAd5. Adverse events (AEs) related to study vaccines were in general mild and limited to one episode of hematuria, Grade two. Activated partial thromboplastin time (aPTT) AEs were consistent with an in vitro effect on the laboratory assay for aPTT due to a transient induction of anti-phospholipid antibody, a phenomenon that has been reported in other adenoviral vector vaccine trials.
Conclusions
Limitations of the rAd vaccine vectors, including the complex interactions among pre-existing adenoviral immunity and vaccine-induced immune responses, have prompted investigators to include less seroprevalent vectors such as rAd35-EnvA in prime-boost regimens. The rAd35-EnvA vaccine described here was well tolerated and immunogenic. While it effectively primed and boosted antibody responses when given in a reciprocal prime-boost regimen with rAd5-EnvA using a three-month interval, it did not significantly improve the frequency or magnitude of T cell responses above a single dose of rAd5. The humoral and cellular immunogenicity data reported here may inform future vaccine and study design.
C1 [Crank, Michelle C.; Wilson, Eleanor M. P.; Novik, Laura; Enama, Mary E.; Hendel, Cynthia S.; Bailer, Robert T.; Nabel, Gary J.; McDermott, Adrian B.; Mascola, John R.; Koup, Richard A.; Ledgerwood, Julie E.; Graham, Barney S.] NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Nason, Martha C.] NIAID, Biostat Res Branch, Div Clin Res, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Gu, Wenjuan] Leidos Biomed Res Inc, Clin Monitoring Res Program, Clin Res Directorate, NCI Campus,Frederick, Frederick, MD 21702 USA.
[Wilson, Eleanor M. P.] Univ Maryland, Sch Med, Inst Human Virol, Baltimore, MD 21201 USA.
[Nabel, Gary J.] Sanofi US, Cambridge, MA USA.
RP Graham, BS (reprint author), NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM bgraham@nih.gov
OI Wilson, Eleanor/0000-0002-4855-514X
FU National Institute of Allergy and Infectious Diseases (NIAID) intramural
research program; National Cancer Institute, National Institutes of
Health [HHSN261200800001E]
FX Funding for the conduct of this clinical trial was provided by the
National Institute of Allergy and Infectious Diseases (NIAID) intramural
research program. The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript. Wenjuan Gu: Ms. Gu is an employee of Clinical Research
Directorate/Clinical Monitoring Research Program, Leidos Biomedical
Research, Inc., NCI Campus at Frederick, Maryland 21702. This project
has been funded in whole or in part with federal funds from the National
Cancer Institute, National Institutes of Health, under Contract No.
HHSN261200800001E. The content of this publication does not necessarily
reflect the views or policies of the Department of Health and Human
Services, nor does mention of trade names, commercial products, or
organizations imply endorsement by the U.S. Government.
NR 61
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U1 1
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PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD NOV 15
PY 2016
VL 11
IS 11
AR e0166393
DI 10.1371/journal.pone.0166393
PG 19
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EC0MG
UT WOS:000387794600056
PM 27846256
ER
PT J
AU Mishra, PJ
Mishra, PJ
Merlino, G
AF Mishra, Prasun J.
Mishra, Pravin J.
Merlino, Glenn
TI Integrated Genomics Identifies miR-32/MCL-1 Pathway as a Critical Driver
of Melanomagenesis: Implications for miR-Replacement and Combination
Therapy
SO PLOS ONE
LA English
DT Article
ID ULTRAVIOLET-RADIATION; MALIGNANT-MELANOMA; SITE POLYMORPHISM;
TUMOR-SUPPRESSOR; RESISTANCE; CELLS; CANCER; MICE; APOPTOSIS; MCL-1
AB Aims
Cutaneous malignant melanoma is among the deadliest human cancers, broadly resistant to most clinical therapies. A majority of patients with BRAF(V600E) melanomas respond well to inhibitors such as vemurafenib, but all ultimately relapse. Moreover, there are no viable treatment options available for other non-BRAF melanoma subtypes in the clinic. A key to improving treatment options lies in a better understanding of mechanisms underlying melanoma progression, which are complex and heterogeneous.
Methods
In this study we integrated gene and microRNA (miRNA) expression data from genetically engineered mouse models of highly and poorly malignant melanocytic tumors, as well as available human melanoma databases, and discovered an important role for a pathway centered on a tumor suppressor miRNA, miR-32.
Results
Malignant tumors frequently exhibited poor expression of miR-32, whose targets include NRAS, PI3K and notably, MCL-1. Accordingly, MCL-1 was often highly expressed in melanomas, and when knocked down diminished oncogenic potential. Forced MCL-1 overexpression transformed immortalized primary mouse melanocytes, but only when also expressing activating mutations in BRAF, CRAF or PI3K. Importantly, both miR-32 replacement therapy and the MCL-1-specific antagonist sabutoclax demonstrated single-agent efficacy, and acted synergistically in combination with vemurafenib in preclinical melanoma models.
Conclusions
We here identify miR-32/ MCL-1 pathway members as key early genetic events driving melanoma progression, and suggest that their inhibition may be an effective anti-melanoma strategy irrespective of NRAS, BRAF, and PTEN status.
C1 [Mishra, Prasun J.] Genentech Inc, Dept Biochem & Cellular Pharmacol, San Francisco, CA 94080 USA.
[Mishra, Prasun J.; Merlino, Glenn] NCI, Lab Canc Biol & Genet, NIH, Bethesda, MD 20892 USA.
[Mishra, Pravin J.] Dixie Reg Med Ctr, Precis Genom, Intermt Healthcare, St George, UT USA.
RP Mishra, PJ (reprint author), Genentech Inc, Dept Biochem & Cellular Pharmacol, San Francisco, CA 94080 USA.; Mishra, PJ; Merlino, G (reprint author), NCI, Lab Canc Biol & Genet, NIH, Bethesda, MD 20892 USA.
EM mishra.prasun@gene.com; gmerlino@helix.nih.gov
FU Intramural Research Program of the Center of Cancer Research, NCI, NIH;
NCI Cancer Research Training Award [C5IL039280]; NCI; Genentech
FX The work was supported by the Intramural Research Program of the Center
of Cancer Research, NCI, NIH, and in part by NCI Cancer Research
Training Award C5IL039280, and NCI Director's Innovation Awards in 2009
and 2011 (to PJM). PJM is employed by Genentech Inc. at present. The
funder provided support in the form of salaries to PJM (Genentech), GM
(NCI), but did not have any additional role in the study design, data
collection and analysis, decision to publish, or preparation of the
manuscript. The specific roles of these authors are articulated in the
'author contributions' section.; The work was supported by the
Intramural Research Program of the Center of Cancer Research, NCI, NIH,
and in part by NCI Cancer Research Training Award C5IL039280, and NCI
Director's Innovation Awards in 2009 and 2011 (to PJM). PJM is employed
by Genentech Inc. at present. The funder provided support in the form of
salaries to PJM (Genentech), GM (NCI), but did not have any additional
role in the study design, data collection and analysis, decision to
publish, or preparation of the manuscript. The specific roles of these
authors are articulated in the 'author contributions' section.
Sabutoclax was a generous gift from Dr. Paul B. Fisher, Virginia
Commonwealth University, Richmond, VA and was also purchased from
APEXBIO. Some of the human melanocytes and melanoma cell lines were
obtained from Dr. Meenhard Herlyn, The Wistar Institute Melanoma
Research Center, PA and from Cell Culture Core Facility, Yale Skin
Diseases Research Center Core, Department of Dermatology, Yale
University School of Medicine.
NR 37
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U1 1
U2 1
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD NOV 15
PY 2016
VL 11
IS 11
AR e0165102
DI 10.1371/journal.pone.0165102
PG 21
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EC0MG
UT WOS:000387794600008
PM 27846237
ER
PT J
AU Lee, JJ
Yin, XY
Hoffmann, U
Fox, CS
Benjamin, EJ
AF Lee, Jane J.
Yin, Xiaoyan
Hoffmann, Udo
Fox, Caroline S.
Benjamin, Emelia J.
TI Relation of Pericardial Fat, Intrathoracic Fat, and Abdominal Visceral
Fat With Incident Atrial Fibrillation (from the Framingham Heart Study)
SO AMERICAN JOURNAL OF CARDIOLOGY
LA English
DT Article
ID EPICARDIAL ADIPOSE-TISSUE; INFLAMMATORY CYTOKINES;
CARDIOVASCULAR-DISEASE; RISK-FACTORS; VOLUME; ASSOCIATION; ABLATION
AB Obesity is associated with increased risk of developing atrial fibrillation (AF). Different fat depots may have differential associations with cardiac pathology. We examined the longitudinal associations between pericardial, intrathoracic, and visceral fat with incident AF. We studied Framingham Heart Study Offspring and Third-Generation Cohorts who participated in the multidetector computed tomography substudy examination 1. We constructed multivariable-adjusted Cox proportional hazard models for risk of incident AF. Body mass index was included in the multivariable-adjusted model as a secondary adjustment. We included 2,135 participants (53.3% women; mean age 58.8 years). During a median follow-up of 9.7 years, we identified 162 cases of incident AF. Across the increasing tertiles of pericardial fat volume, age- and gender-adjusted incident AF rate per 1,000 person-years of follow-up were 8.4, 7.5, and 10.2. Based on an age- and gender-adjusted model, greater pericardial fat (hazard ratio [BR] 1.17, 95% confidence interval [CI] 1.03 to 1.34) and intrathoracic fat (HR 1.24, 95% CI 1.06 to 1.45) were associated with an increased risk of incident AF. The BRs (95% CI) for incident AF were 1.13 (0.99 to 1.30) for pericardial fat, 1.19 (1.01 to 1.40) for intrathoracic fat, and 1.09 (0.93 to 1.28) for abdominal visceral fat after multivariable adjustment. After additional adjustment of body mass index, none of the associations remained significant (all p >0.05). Our findings suggest that cardiac ectopic fat depots may share common risk factors with AF, which may have led to a lack of independence in the association between pericardial fat with incident AF. (C) 2016 Elsevier Inc. All rights reserved.
C1 [Lee, Jane J.; Yin, Xiaoyan; Fox, Caroline S.; Benjamin, Emelia J.] NHLBI, Populat Sci Branch, Div Intramural Res, Framingham, MA 01702 USA.
[Yin, Xiaoyan; Benjamin, Emelia J.] Boston Univ Framingham Heart Study, Framingham, MA 01702 USA.
[Hoffmann, Udo] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA.
[Fox, Caroline S.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA USA.
[Benjamin, Emelia J.] Harvard Med Sch, Brigham & Womens Hosp, Div Endocrinol, Boston, MA USA.
[Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.
RP Benjamin, EJ (reprint author), NHLBI, Populat Sci Branch, Div Intramural Res, Framingham, MA 01702 USA.; Benjamin, EJ (reprint author), Boston Univ Framingham Heart Study, Framingham, MA 01702 USA.; Benjamin, EJ (reprint author), Harvard Med Sch, Brigham & Womens Hosp, Div Endocrinol, Boston, MA USA.
EM emelia@bu.edu
OI Benjamin, Emelia/0000-0003-4076-2336
FU National Heart, Lung and Blood Institute's Framingham Heart Study
(Framingham, Massachusetts) [N01-HC-25195]; National Institutes of
Health [HHSN268201500001I, 2R01HL092577, 1R01 HL128914, 1R01 HL102214,
1RC1HL101056]
FX This work was supported by the National Heart, Lung and Blood
Institute's Framingham Heart Study (Framingham, Massachusetts) (contract
N01-HC-25195). Dr. Emelia Benjamin is supported by grants
HHSN268201500001I, 2R01HL092577, 1R01 HL128914, 1R01 HL102214,
1RC1HL101056 from the National Institutes of Health.
NR 30
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U1 1
U2 1
PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC
PI BRIDGEWATER
PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA
SN 0002-9149
EI 1879-1913
J9 AM J CARDIOL
JI Am. J. Cardiol.
PD NOV 15
PY 2016
VL 118
IS 10
BP 1486
EP 1492
DI 10.1016/j.amjcard.2016.08.011
PG 7
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA ED7DM
UT WOS:000389015900009
PM 27666172
ER
PT J
AU Ko, D
Riles, EM
Marcos, EG
Magnani, JW
Lubitz, SA
Lin, HH
Long, MT
Schnabel, RB
McManus, DD
Ellinor, PT
Ramachandran, VS
Wang, TJ
Gerszten, RE
Benjamin, EJ
Yin, XY
Rienstra, M
AF Ko, Darae
Riles, Eric M.
Marcos, Ernaldo G.
Magnani, Jared W.
Lubitz, Steven A.
Lin, Honghuang
Long, Michelle T.
Schnabel, Renate B.
McManus, David D.
Ellinor, Patrick T.
Ramachandran, Vasan S.
Wang, Thomas J.
Gerszten, Robert E.
Benjamin, Emelia J.
Yin, Xiaoyan
Rienstra, Michiel
TI Metabolomic Profiling in Relation to New-Onset Atrial Fibrillation (from
the Framingham Heart Study)
SO AMERICAN JOURNAL OF CARDIOLOGY
LA English
DT Article
ID SERUM URIC-ACID; OXIDATIVE STRESS; RISK; BIOMARKER; FAILURE
AB Previous studies have shown several metabolic biomarkers to be associated with prevalent and incident atrial fibrillation (AF), but the results have not been replicated.. We investigated metabolite profiles of 2,458 European ancestry participants from the Framingham Heart Study without AF at the index examination and followed them for 10 years for new onset AF. Amino acids, organic acids, lipids, and other plasma metabolites were profiled by liquid chromatography tandem mass spectrometry using fasting plasma samples. We conducted Cox proportional hazard analyses for association between metabolites and new onset AF. We performed hypothesis-generating analysis to identify novel metabolites and hypothesis-testing analysis to confirm the previously reported associations between metabolites and AF. Mean age was 55.1 +/- 9.9 years, and 53% were women. Incident AF developed in 156 participants (6.3%) in 10 years of follow-up. A total of 217 metabolites were examined, consisting of 54 positively charged metabolites, 59 negatively charged metabolites, and 104 lipids. None of the 217 metabolites met our a priori specified Bonferroni corrected level of significance in the multivariate analyses. We were unable to replicate previous results demonstrating associations between metabolites that we had measured and AF. In conclusion, in our metabolomics approach, none of the metabolites we tested were significantly associated with the risk of future AF. (C) 2016 Elsevier Inc. All rights reserved.
C1 [Ko, Darae] Boston Univ, Sch Med, Boston Med Ctr, Dept Internal Med,Gen Internal Med Sect, Boston, MA 02118 USA.
[Riles, Eric M.; Magnani, Jared W.; Ramachandran, Vasan S.; Benjamin, Emelia J.] Boston Univ, Sch Med, Boston Med Ctr, Dept Internal Med,Sect Cardiovasc Med, Boston, MA 02118 USA.
[Long, Michelle T.] Boston Univ, Sch Med, Boston Med Ctr, Dept Internal Med,Gastroenterol Sect, Boston, MA 02118 USA.
[Ramachandran, Vasan S.; Benjamin, Emelia J.] Boston Univ, Sch Med, Boston Med Ctr, Dept Internal Med,Sect Prevent Med, Boston, MA 02118 USA.
[Ko, Darae; Ramachandran, Vasan S.; Benjamin, Emelia J.] Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Boston, MA 02118 USA.
[Ko, Darae] Boston Univ, Sch Med, Clin & Translat Sci Inst, Boston, MA 02118 USA.
[Marcos, Ernaldo G.; Rienstra, Michiel] Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, Groningen, Netherlands.
[Lubitz, Steven A.; Ellinor, Patrick T.; Gerszten, Robert E.] Harvard Med Sch, Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA USA.
[Lubitz, Steven A.; Ellinor, Patrick T.] Harvard Med Sch, Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA USA.
[Ramachandran, Vasan S.; Benjamin, Emelia J.] Boston Univ, Framingham, MA USA.
[Ramachandran, Vasan S.; Benjamin, Emelia J.] Natl Heart Lung & Blood Inst Framingham Heart Stu, Framingham, MA USA.
[Schnabel, Renate B.] Univ Hamburg, Heart Ctr Hamburg Eppendorf, Dept Gen & Intervent Cardiol, Hamburg, Germany.
[McManus, David D.] Univ Massachusetts, Sch Med, Div Cardiovasc Med, Worcester, MA USA.
[Ramachandran, Vasan S.; Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.
[Wang, Thomas J.] Vanderbilt Univ, Div Cardiovasc Med, 221 Kirkland Hall, Nashville, TN 37235 USA.
[Yin, Xiaoyan] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
RP Rienstra, M (reprint author), Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, Groningen, Netherlands.
EM m.rienstra@umcg.nl
OI Rienstra, Michiel/0000-0002-2581-070X
FU NIH/NHLBI [HHSN268201500001I, N01-HC25195, 2R01HL092577, 1R01 HL102214,
1R01HL128914, 1RC1HL101056]; National Institutes of Health
[2R01HL092577, 1K24HL105780]; Established Investigator Award from the
American Heart Association [13EIA14220013]; Fondation Leducq [14CVD01];
NIH Career Development Award [K23HL114724]; Doris Duke Charitable
Foundation Clinical Scientist Development Award [2014105, 2015084];
European Research Council under the European Union's Horizon research
and innovation program [648131]; German Ministry of Research and
Education [BMBF 01ZX1408A]; German Research Foundation Emmy Noether
Program [SCHN 1149/3-1]; Netherlands Organization for Scientific
Research [616.136.055]; NIH [R01-DK-HL081572]; [5T32HL007224-38];
[UL1-TR000157]
FX Dr. Ko is supported by 5T32HL007224-38 and UL1-TR000157. Dr. Benjamin is
supported in part through NIH/NHLBI HHSN268201500001I; N01-HC25195,
2R01HL092577, 1R01 HL102214, 1R01HL128914, and 1RC1HL101056. Dr. Ellinor
is supported by grants from the National Institutes of Health
(2R01HL092577, 1K24HL105780), an Established Investigator Award from the
American Heart Association (13EIA14220013), and the Fondation Leducq
(14CVD01). Dr. Lubitz is supported by an NIH Career Development Award
(K23HL114724) and Doris Duke Charitable Foundation Clinical Scientist
Development Award (2014105). Dr. Magnani is supported by a Doris Duke
Charitable Foundation Clinical Scientist Development Award (2015084).
Dr. R. Schnabel has received funding from the European Research Council
under the European Union's Horizon 2020 research and innovation program
(grant agreement No 648131), German Ministry of Research and Education
(BMBF 01ZX1408A), German Research Foundation Emmy Noether Program SCHN
1149/3-1. Dr. Rienstra is supported by a grant from the Netherlands
Organization for Scientific Research (Veni grant 616.136.055). The
project was funded by NIH R01-DK-HL081572.
NR 25
TC 0
Z9 0
U1 2
U2 2
PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC
PI BRIDGEWATER
PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA
SN 0002-9149
EI 1879-1913
J9 AM J CARDIOL
JI Am. J. Cardiol.
PD NOV 15
PY 2016
VL 118
IS 10
BP 1493
EP 1496
DI 10.1016/j.amjcard.2016.08.010
PG 4
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA ED7DM
UT WOS:000389015900010
PM 27666170
ER
PT J
AU Massett, HA
Mishkin, G
Rubinstein, L
Ivy, SP
Denicoff, A
Godwin, E
DiPiazza, K
Bolognese, J
Zwiebel, JA
Abrams, JS
AF Massett, Holly A.
Mishkin, Grace
Rubinstein, Larry
Ivy, S. Percy
Denicoff, Andrea
Godwin, Elizabeth
DiPiazza, Kate
Bolognese, Jennifer
Zwiebel, James A.
Abrams, Jeffrey S.
TI Challenges Facing Early Phase Trials Sponsoredby the National Cancer
Institute: An Analysis of Corrective Action Plans to Improve Accrual
SO CLINICAL CANCER RESEARCH
LA English
DT Review
ID CLINICAL-TRIALS; RECRUITMENT
AB Accruing patients in a timely manner represents a significant challenge to early phase cancer clinical trials. The NCI Cancer Therapy Evaluation Program analyzed 19 months of corrective action plans (CAP) received for slow-accruing phase I and II trials to identify slow accrual reasons, evaluate whether proposed corrective actions matched these reasons, and assess the CAP impact on trial accrual, duration, and likelihood of meeting primary scientific objectives. Of the 135 CAPs analyzed, 69 were for phase I trials and 66 for phase II trials. Primary reasons cited for slow accrual were safety/toxicity (phase I: 48%), design/protocol concerns (phase I: 42%, phase II: 33%), and eligibility criteria (phase I: 41%, phase II: 35%). The most commonly proposed corrective actions were adding institutions (phase I: 43%, phase II: 85%) and amending the trial to change eligibility or design (phase I: 55%, phase II: 44%). Only 40% of CAPs provided proposed corrective actions that matched the reasons given for slow accrual. Seventy percent of trials were closed to accrual at time of analysis (phase I = 48; phase II = 46). Of these, 67% of phase I and 70% of phase II trials met their primary objectives, but they were active three times longer than projected. Among closed trials, 24% had an accrual rate increase associated with a greater likelihood of meeting their primary scientific objectives. Ultimately, trials receiving CAPs saw improved accrual rates. Future trials may benefit from implementing CAPs early in trial life cycles, but it may be more beneficial to invest in earlier accrual planning.
C1 [Massett, Holly A.; Mishkin, Grace; Rubinstein, Larry; Ivy, S. Percy; Denicoff, Andrea; Zwiebel, James A.; Abrams, Jeffrey S.] NCI, Bethesda, MD 20892 USA.
[Godwin, Elizabeth; DiPiazza, Kate] Emmes Corp, Rockville, MD USA.
[Bolognese, Jennifer] Westat Corp, Rockville, MD USA.
RP Massett, HA (reprint author), NCI, 9609 Med Ctr Dr,Room 5W562, Rockville, MD 20850 USA.
EM massetth@mail.nih.gov
FU National Cancer Institute at the National Institutes of Health
FX The authors acknowledge the support of the National Cancer Institute at
the National Institutes of Health.
NR 36
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U1 1
U2 1
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 NOV 15
PY 2016
VL 22
IS 22
BP 5408
EP 5416
DI 10.1158/1078-0432.CCR-16-0338
PG 9
WC Oncology
SC Oncology
GA ED3IU
UT WOS:000388743600004
PM 27401246
ER
PT J
AU Mansfield, AS
Rudek, MA
Vulih, D
Smith, GL
Harris, PJ
Ivy, SP
AF Mansfield, Aaron S.
Rudek, Michelle A.
Vulih, Diana
Smith, Gary L.
Harris, Pamela Jo
Ivy, S. Percy
CA NCI Organ Dysfunction Working Grp
TI The Effect of Hepatic Impairment on Outcomes in Phase I Clinical Trials
in Cancer Subjects
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID DYSFUNCTION WORKING GROUP; ADVANCED SOLID TUMORS; STAGE LIVER-DISEASE;
ADVANCED MALIGNANCIES; VARYING DEGREES; AMINOTRANSFERASE LEVELS;
PHARMACOKINETIC TRIAL; RENAL DYSFUNCTION; IMATINIB MESYLATE; OXALIPLATIN
AB Purpose: The NCI Cancer Therapy Evaluation Program sponsors hepatic dysfunction phase I clinical trials (HDCT) and phase 1 clinical trials (P1CT) to determine safe doses and schedules of antineoplastic therapeutics. We sought to compare clinical outcomes between these trial types while stratifying by hepatotoxic agents.
Experimental Design: Individual subject data were extracted from the records of 51 NCI-sponsored HDCT and P1CT. The NCI's Organ Dysfunction Working Group's hepatic impairment categorization and two drug-induced liver injury (DILI) scales (FDA R ratio and Hy's law) were used to classify subjects. The number of cycles administered and treatment discontinuation reason were also evaluated and compared between groups.
Results: There were 513 and 1,328 subjects treated on HDCT (n = 9) and P1CT (n = 42), respectively. There were differing patterns of DILI with significant worsening of total bilirubin in subjects on HDCT, and worsening of alanine aminotransferase (ALT) in subjects on P1CT. Cholestatic peak patterns of liver impairment (predominant increases in alkaline phosphatase rather than transaminases) were more frequent in HDCT. Criteria for Hy's law were met by 11 subjects on P1CT, but not by any subjects on HDCT. Disease progression was the most common reason for treatment discontinuation, followed by adverse events at similar frequencies in both HDCT and P1CT.
Conclusions: The differential effects on hepatotoxicity suggest that underlying hepatic function may affect susceptibility to and patterns of DILI. The incorporation of additional measures of hepatic function may help identify those at highest risk of hepatotoxicity in future trials because baseline liver tests did not. (C)2016 AACR.
C1 [Mansfield, Aaron S.] Mayo Clin, Div Med Oncol, Rochester, MN USA.
[Rudek, Michelle A.] Johns Hopkins Univ, Sch Med, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA.
[Vulih, Diana] Theradex, Princeton, NJ USA.
[Smith, Gary L.] NCI, Clin Trials Monitoring Branch, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA.
[Harris, Pamela Jo; Ivy, S. Percy] NCI, Invest Drug Branch, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA.
RP Mansfield, AS (reprint author), Mayo Clin, 200 First St SW, Rochester, MN 55905 USA.
EM mansfield.aaron@mayo.edu
FU NIH [K12CA090628, UM1CA186691, P30CA006973]
FX This work was supported by NIH grants K12CA090628 (A.S. Mansfield),
UM1CA186691 (M.A. Rudek), and P30CA006973 (M.A. Rudek).
NR 30
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U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
EI 1557-3265
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD NOV 15
PY 2016
VL 22
IS 22
BP 5472
EP 5479
DI 10.1158/1078-0432.CCR-16-0449
PG 8
WC Oncology
SC Oncology
GA ED3IU
UT WOS:000388743600012
PM 27189163
ER
PT J
AU Xi, LQ
Pham, THT
Payabyab, EC
Sherry, RM
Rosenberg, SA
Raffeld, M
AF Xi, Liqiang
Pham, Trinh Hoc-Tran
Payabyab, Eden C.
Sherry, Richard M.
Rosenberg, Steven A.
Raffeld, Mark
TI Circulating Tumor DNA as an Early Indicator of Response to T-cell
Transfer Immunotherapy in Metastatic Melanoma
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID DROPLET DIGITAL PCR; SERUM; BRAF; MUTATIONS; PLASMA; CANCER;
LYMPHOCYTES; RESISTANCE; THERAPY
AB Purpose: Adoptive transfer of activated autologous tumor-infiltrating lymphocytes (TIL) can mediate complete, durable regressions in patients with metastatic melanoma. Responding patients generally do not have significant changes in noncutaneous RECIST targets before 30 to 60 days following TIL infusion, and complete responses are often not confirmed for 1 to 2 years. There is a critical need for a biomarker that can provide early information regarding the likelihood and duration of a response to enable rational decisions about altering therapy. We wished to evaluate the role of circulating tumor DNA (ctDNA) in separating responding from nonresponding patients.
Experimental Design: We studied BRAF V600E ctDNA levels by a sensitive allele-specific PCR assay in 388 serum samples from 48 patients who received TIL immunotherapy at the NCI and correlated differences in the dynamic patterns of their ctDNA measurements with response outcomes.
Results: A strong correlation was found between the presence or absence of an early serum peak of V600E ctDNA, and the likelihood of an objective response. Furthermore, patients that developed an early ctDNA peak and cleared their serum of V600E ctDNA were highly likely to achieve a complete response over the next 1 to 2 years. Patients that showed no peak of V600E ctDNA failed to achieve an objective response, with one exception.
Conclusions: We show that the dynamic changes occurring in BRAF V600E ctDNA levels within the first month following T-cell transfer immunotherapy in metastatic melanoma can be used to rapidly identify responding from nonresponding patients, potentially allowing clinicians to make critical treatment-related decisions in a more timely manner. These data also suggest that the majority of tumor killing by TIL occurs very early after the initiation of therapy. (C)2016 AACR.
C1 [Xi, Liqiang; Pham, Trinh Hoc-Tran; Raffeld, Mark] NCI, Mol Diagnost Sect, Pathol Lab, Ctr Canc Res,NIH, Bldg 10,Room 3S235E,10 Ctr Dr, Bethesda, MD 20892 USA.
[Payabyab, Eden C.; Sherry, Richard M.; Rosenberg, Steven A.] NCI, Surg Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Raffeld, M (reprint author), NCI, Mol Diagnost Sect, Pathol Lab, Ctr Canc Res,NIH, Bldg 10,Room 3S235E,10 Ctr Dr, Bethesda, MD 20892 USA.
EM mraff@mail.nih.gov
NR 28
TC 1
Z9 1
U1 4
U2 4
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 NOV 15
PY 2016
VL 22
IS 22
BP 5480
EP 5486
DI 10.1158/1078-0432.CCR-16-0613
PG 7
WC Oncology
SC Oncology
GA ED3IU
UT WOS:000388743600013
PM 27482033
ER
PT J
AU Ooms, AHAG
Gadd, S
Gerhard, DS
Smith, MA
Auvil, JMG
Meerzaman, D
Chen, QR
Hsu, CH
Yan, C
Nguyen, C
Hu, Y
Ma, Y
Zong, Z
Mungall, AJ
Moore, RA
Marra, MA
Huff, V
Dome, JS
Chi, YY
Tian, J
Geller, JI
Mullighan, CG
Ma, J
Wheeler, DA
Hampton, OA
Walz, AL
van den Heuvel-Eibrink, MM
de Krijger, RR
Ross, N
Gastier-Foster, J
Perlman, EJ
AF Ooms, Ariadne H. A. G.
Gadd, Samantha
Gerhard, Daniela S.
Smith, Malcolm A.
Auvil, Jaime M. Guidry
Meerzaman, Daoud
Chen, Qing-Rong
Hsu, Chih Hao
Yan, Chunhua
Nguyen, Cu
Hu, Ying
Ma, Yussanne
Zong, Zusheng
Mungall, Andrew J.
Moore, Richard A.
Marra, Marco A.
Huff, Vicki
Dome, Jeffrey S.
Chi, Yueh-Yun
Tian, Jing
Geller, James I.
Mullighan, Charles G.
Ma, Jing
Wheeler, David A.
Hampton, Oliver A.
Walz, Amy L.
van den Heuvel-Eibrink, Marry M.
de Krijger, Ronald R.
Ross, Nicole
Gastier-Foster, JulieM.
Perlman, Elizabeth J.
TI Significance of TP53 Mutation in Wilms Tumors with Diffuse Anaplasia: A
Report from the Children's Oncology Group
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID P53 GENE-MUTATIONS; PROGNOSTIC-FACTOR; POOR-PROGNOSIS; EXPRESSION;
ALIGNMENT; GENOME; IMMUNOHISTOCHEMISTRY; TETRAMERIZATION; PATTERNS; GAIN
AB Purpose: To investigate the role and significance of TP53 mutation in diffusely anaplastic Wilms tumors (DAWTs).
Experimental Design: All DAWTs registered on National Wilms Tumor Study-5 (n = 118) with available samples were analyzed for TP53 mutations and copy loss. Integrative genomic analysis was performed on 39 selected DAWTs.
Results: Following analysis of a single random sample, 57 DAWTs (48%) demonstrated TP53 mutations, 13 (11%) copy loss without mutation, and 48 (41%) lacked both [defined as TP53-wild-type (wt)]. Patients with stage III/IV TP53-wt DAWTs (but not those with stage I/II disease) had significantly lower relapse and death rates than those with TP53 abnormalities. Indepth analysis of a subset of 39 DAWTs showed seven (18%) to be TP53-wt: These demonstrated gene expression evidence of an active p53 pathway. Retrospective pathology review of TP53-wt DAWT revealed no or very low volume of anaplasia in six of seven tumors. When samples from TP53-wt tumors known to contain anaplasia histologically were available, abnormal p53 protein accumulation was observed by immunohistochemistry.
Conclusions: These data support the key role of TP53 loss in the development of anaplasia in WT, and support its significant clinical impact in patients with residual anaplastic tumor following surgery. These data also suggest that most DAWTs will show evidence of TP53 mutation when samples selected for the presence of anaplasia are analyzed. This suggests that modifications of the current criteria to also consider volume of anaplasia and documentation of TP53 aberrations may better reflect the risk of relapse and death and enable optimization of therapeutic stratification. (C) 2016 AACR.
C1 [Ooms, Ariadne H. A. G.; Gadd, Samantha; Perlman, Elizabeth J.] Northwestern Univ, Dept Pathol & Lab Med, Ann & Robert H Lurie Childrens Hosp Chicago, Robert H Lurie Canc Ctr, Chicago, IL 60611 USA.
[Ooms, Ariadne H. A. G.; van den Heuvel-Eibrink, Marry M.; de Krijger, Ronald R.] Princess Maxima Ctr Pediat Oncol, Utrecht, Netherlands.
[Ooms, Ariadne H. A. G.] Pathan BV, Dept Pathol, Rotterdam, Netherlands.
[Gerhard, Daniela S.; Auvil, Jaime M. Guidry] NCI, Off Canc Genom, Bethesda, MD 20892 USA.
[Smith, Malcolm A.] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA.
[Meerzaman, Daoud; Chen, Qing-Rong; Hsu, Chih Hao; Yan, Chunhua; Nguyen, Cu; Hu, Ying] NCI, Ctr Biomed Informat & Informat Technol, Bethesda, MD 20892 USA.
[Ma, Yussanne; Zong, Zusheng; Mungall, Andrew J.; Moore, Richard A.; Marra, Marco A.] BCCA, Canadas Michael Smith Genome Sci Ctr, Vancouver, BC, Canada.
[Marra, Marco A.] Univ British Columbia, Dept Med Genet, Vancouver, BC, Canada.
[Huff, Vicki] Univ Texas MD Anderson Canc Ctr, Dept Genet, Houston, TX 77030 USA.
[Dome, Jeffrey S.] Childrens Natl Med Ctr, Div Pediat Hematol Oncol, Washington, DC 20010 USA.
[Chi, Yueh-Yun; Tian, Jing] Univ Florida, Dept Biostat, Gainesville, FL USA.
[Geller, James I.] Univ Cincinnati, Cincinnati Childrens Hosp Med Ctr, Div Pediat Oncol, Cincinnati, OH USA.
[Mullighan, Charles G.; Ma, Jing] St Jude Childrens Res Hosp, Dept Pathol, 332 N Lauderdale St, Memphis, TN 38105 USA.
[Wheeler, David A.; Hampton, Oliver A.] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA.
[Walz, Amy L.] Northwestern Univ, Div Hematol Oncol & Transplantat, Ann & Robert H Lurie Childrens Hosp Chicago, Feinberg Sch Med, Chicago, IL 60611 USA.
[Walz, Amy L.] Northwestern Mem Hosp, Northwestern Med Dev Therapeut Inst, Chicago, IL USA.
[de Krijger, Ronald R.] Reinier de Graaf Hosp, Dept Pathol, Delft, Netherlands.
[Ross, Nicole; Gastier-Foster, JulieM.] Ohio State Univ, Coll Med, Nationwide Childrens Hosp, Dept Pathol & Lab Med, Columbus, OH 43210 USA.
[Gastier-Foster, JulieM.] Ohio State Univ, Coll Med, Dept Pathol, Columbus, OH 43210 USA.
[Gastier-Foster, JulieM.] Ohio State Univ, Coll Med, Dept Pediat, Columbus, OH 43210 USA.
RP Perlman, EJ (reprint author), Ann & Robert H Lurie Childrens Hosp, 225 East Chicago Ave, Chicago, IL 60611 USA.
EM Eperlman@luriechildrens.org
RI Marra, Marco/B-5987-2008
FU NCI [U10 CA98543, T32 CA079447]; US NIH [The Children's Oncology Group]
[NIH U10CA180886, NIHU10CA180899, NIH U10CA098413, NIHU10CA42326,
U10CA98543, U24 CA114766, UO1CA88131, HHSN261200800001E]; Dutch Cancer
Society; American and Lebanese Syrian Associated Charities of St. Jude;
WGS (CGI, Inc.); WES (Baylor College of Medicine); miRNAseq; RNAseq
FX The TARGET initiative is supported by NCI Grant U10 CA98543. Work
performed under contracts from the NCI (T32 CA079447, to A.L. Walz), US
NIH [The Children's Oncology Group award numbers NIH U10CA180886,
NIHU10CA180899; NIH U10CA098413; NIHU10CA42326 (E.J. Perlman);
U10CA98543 (to J.S. Dome and E.J. Perlman); U24 CA114766; UO1CA88131
(E.J. Perlman)] within HHSN261200800001E includes specimen processing
(the COG BPC), WGS (CGI, Inc.), WES (Baylor College of Medicine),
miRNAseq, RNAseq, and target capture sequencing (BCCA Genome Sciences
Center). This study was also supported by Dutch Cancer Society (to
A.H.A.G. Ooms) and American and Lebanese Syrian Associated Charities of
St. Jude (to C.G. Mullighan and Jing Ma).
NR 47
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
EI 1557-3265
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD NOV 15
PY 2016
VL 22
IS 22
BP 5582
EP 5591
DI 10.1158/1078-0432.CCR-16-0985
PG 10
WC Oncology
SC Oncology
GA ED3IU
UT WOS:000388743600023
PM 27702824
ER
PT J
AU Pavlou, HJ
Lin, AC
Neville, MC
Nojima, T
Diao, F
Chen, BE
White, BH
Goodwin, SF
AF Pavlou, Hania J.
Lin, Andrew C.
Neville, Megan C.
Nojima, Tetsuya
Diao, Fengqiu
Chen, Brian E.
White, Benjamin H.
Goodwin, Stephen F.
TI Neural circuitry coordinating male copulation
SO ELIFE
LA English
DT Article
ID GLUTAMIC-ACID DECARBOXYLASE; MALE COURTSHIP BEHAVIOR; CENTRAL
NERVOUS-SYSTEM; DROSOPHILA-MELANOGASTER; SPECTRAL PREFERENCE;
FUNCTIONAL-ANALYSIS; EXPRESSING NEURONS; SPERM TRANSFER; DOUBLESEX;
FRUITLESS
AB Copulation is the goal of the courtship process, crucial to reproductive success and evolutionary fitness. Identifying the circuitry underlying copulation is a necessary step towards understanding universal principles of circuit operation, and how circuit elements are recruited into the production of ordered action sequences. Here, we identify key sex-specific neurons that mediate copulation in Drosophila, and define a sexually dimorphic motor circuit in the male abdominal ganglion that mediates the action sequence of initiating and terminating copulation. This sexually dimorphic circuit composed of three neuronal classes motor neurons, interneurons and mechanosensory neurons controls the mechanics of copulation. By correlating the connectivity, function and activity of these neurons we have determined the logic for how this circuitry is coordinated to generate this male-specific behavior, and sets the stage for a circuit-level dissection of active sensing and modulation of copulatory behavior.
C1 [Pavlou, Hania J.; Lin, Andrew C.; Neville, Megan C.; Nojima, Tetsuya; Goodwin, Stephen F.] Univ Oxford, Ctr Neural Circuits & Behav, Oxford, England.
[Lin, Andrew C.] Univ Sheffield, Dept Biomed Sci, Sheffield, S Yorkshire, England.
[Diao, Fengqiu; White, Benjamin H.] NIMH, Mol Biol Lab, Bethesda, MD 20892 USA.
[Chen, Brian E.] McGill Univ, Dept Med, Montreal, PQ, Canada.
[Chen, Brian E.] McGill Univ, Dept Neurol & Neurosurg, Montreal, PQ, Canada.
[Pavlou, Hania J.] Univ Oxford, Weatherall Inst Mol Med, MRC Ctr Computat Biol, Oxford, England.
RP Pavlou, HJ; Goodwin, SF (reprint author), Univ Oxford, Ctr Neural Circuits & Behav, Oxford, England.; Pavlou, HJ (reprint author), Univ Oxford, Weatherall Inst Mol Med, MRC Ctr Computat Biol, Oxford, England.
EM hania.pavlou@imm.ox.ac.uk; stephen.goodwin@dpag.ox.ac.uk
OI Lin, Andrew/0000-0001-6310-9765
FU EP Abraham Cephalosporin Trust Fund; Brain@McGill Collaboration Fund;
National Institute of Mental Health [ZIAMH002800]; Wellcome Trust
[WT106189MA]
FX EP Abraham Cephalosporin Trust Fund Hania J Pavlou Stephen F Goodwin;
Brain@McGill Collaboration Fund Hania J Pavlou Brian E Chen Stephen F
Goodwin; National Institute of Mental Health ZIAMH002800 Benjamin H
White; Wellcome Trust WT106189MA Stephen F Goodwin; The funders had no
role in study design, data collection and interpretation, or the
decision to submit the work for publication.
NR 60
TC 1
Z9 1
U1 3
U2 3
PU ELIFE SCIENCES PUBLICATIONS LTD
PI CAMBRIDGE
PA SHERATON HOUSE, CASTLE PARK, CAMBRIDGE, CB3 0AX, ENGLAND
SN 2050-084X
J9 ELIFE
JI eLife
PD NOV 15
PY 2016
VL 5
AR e20713
DI 10.7554/eLife.20713
PG 26
WC Biology
SC Life Sciences & Biomedicine - Other Topics
GA ED2NR
UT WOS:000388684300001
ER
PT J
AU Zhao, GH
Zhu, PP
Renvoise, B
Maldonado-Baez, L
Park, SH
Blackstone, C
AF Zhao, Guohua
Zhu, Peng-Peng
Renvoise, Benoit
Maldonado-Baez, Lymarie
Park, Seong Hee
Blackstone, Craig
TI Mammalian knock out cells reveal prominent roles for atlastin GTPases in
ER network morphology
SO EXPERIMENTAL CELL RESEARCH
LA English
DT Article
DE Endoplasmic reticulum; Hereditary spastic paraplegia; Lipid droplet;
GTPase; CRISPR/Cas9; Morphology
ID HEREDITARY SPASTIC PARAPLEGIA; REGULATES SYNAPTIC GROWTH;
ENDOPLASMIC-RETICULUM; PHARMACOLOGICAL RESCUE; SENSORY NEUROPATHY;
GOLGI-APPARATUS; MEMBRANE-FUSION; ARABIDOPSIS; RHD3; MUTATION
AB Atlastins are large, membrane-bound GTPases that participate in the fusion of endoplasmic reticulum (ER) tubules to generate the polygonal ER network in eukaryotes. They also regulate lipid droplet size and inhibit bone morphogenetic protein (BMP) signaling, though mechanisms remain unclear. Humans have three atlastins (ATLI, ATL2, and ATL3), and ATLI and ATL3 are mutated in autosomal dominant hereditary spastic paraplegia and hereditary sensory neuropathies, Cellular investigations of atlastin orthologs in most yeast, plants, flies and worms are facilitated by the presence of a single or predominant isoform, but loss-of-function studies in mammalian cells are complicated by multiple, broadly-expressed paralogs. We have generated mouse NIH-3T3 cells lacking all three mammalian atlastins (Atl 1/2/3) using CRISPR/Cas9-mediated gene knockout (KO). ER morphology is markedly disrupted in these triple KO cells, with prominent impairment in formation of three-way ER tubule junctions. This phenotype can be rescued by expression of distant orthologs from Saccharomyces cereuisiae (Seylp) and Arabidopsis (ROOT HAIR DEFECTIVE3) as well as any one of the three human atlastins. Minimal, if any, changes are observed in the morphology of mitochondria and the Golgi apparatus. Alterations in BMP signaling and increased sensitivity to ER stress are also noted, though effects appear more modest. Finally, atlastins appear required for the proper differentiation of NIH-3T3 cells into an adipocyte-like phenotype. These findings have important implications for the pathogenesis of hereditary spastic paraplegias and sensory neuropathies associated with atlastin mutations.
C1 [Zhao, Guohua; Zhu, Peng-Peng; Renvoise, Benoit; Maldonado-Baez, Lymarie; Park, Seong Hee; Blackstone, Craig] NINDS, Cell Biol Sect, Neurogenet Branch, NIH, Bethesda, MD 20892 USA.
[Zhao, Guohua] Zhejiang Univ, Affiliated Hosp 2, Sch Med, Dept Neurol, Yiwu, Peoples R China.
[Zhao, Guohua] Zhejiang Univ, Affiliated Hosp 4, Sch Med, Dept Neurol, Yiwu, Peoples R China.
[Park, Seong Hee] Bridge Biotherapeut Inc, Seongnam Si, South Korea.
RP Blackstone, C (reprint author), NINDS, Neurogenet Branch, NIH, Bldg 35,Room 2A-201,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM blackstc@ninds.nih.gov
FU Intramural Research Program of the National Institute of Neurological
Disorders and Stroke, National Institutes of Health [NS002992]
FX We thank Chunxin Wang for assistance in generating the knock out cell
lines, Dragan Maric for flow cytometry, and Xufeng Wu for assistance
with super-resolution microscopy. This work was supported by the
Intramural Research Program of the National Institute of Neurological
Disorders and Stroke, National Institutes of Health [ZIA NS002992].
NR 46
TC 0
Z9 0
U1 2
U2 2
PU ELSEVIER INC
PI SAN DIEGO
PA 525 B STREET, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0014-4827
EI 1090-2422
J9 EXP CELL RES
JI Exp. Cell Res.
PD NOV 15
PY 2016
VL 349
IS 1
BP 32
EP 44
DI 10.1016/j.yexcr.2016.09.015
PG 13
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA ED0SY
UT WOS:000388553400004
PM 27669642
ER
PT J
AU Goo, L
Dowd, KA
Lin, TY
Mascola, JR
Graham, BS
Ledgerwood, JE
Pierson, TC
AF Goo, Leslie
Dowd, Kimberly A.
Lin, Tsai-Yu
Mascola, John R.
Graham, Barney S.
Ledgerwood, Julie E.
Pierson, Theodore C.
TI A Virus-Like Particle Vaccine Elicits Broad Neutralizing Antibody
Responses in Humans to All Chikungunya Virus Genotypes
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
DE chikungunya virus; neutralizing antibodies; virus-like particle vaccine
ID EMERGENCE; INFECTION; EPIDEMIC
AB Chikungunya virus (CHIKV) is an alphavirus that has emerged as a global health burden. There are 3 CHIKV genotypes: Asian, West African, and Eastern/Central/South African. No licensed CHIKV vaccine is available, and whether the antibody response elicited by one genotype can neutralize heterologous genotypes is unclear. We assessed neutralizing antibody (NAb) responses of volunteers in a phase 1 study of a CHIKV vaccine against 9 viral strains representing all 3 genotypes. Minimal differences in vaccine-elicited NAb responses were observed among genotypes, suggesting that vaccination with a single CHIKV strain can elicit cross-protective NAbs against all 3 genotypes.
C1 [Goo, Leslie; Dowd, Kimberly A.; Lin, Tsai-Yu; Pierson, Theodore C.] NIAID, Viral Pathogenesis Sect, Viral Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Mascola, John R.; Graham, Barney S.; Ledgerwood, Julie E.] NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Lin, Tsai-Yu] Immune Design, Seattle, WA USA.
RP Pierson, TC (reprint author), NIH, Viral Pathogenesis Sect, Viral Dis Lab, 33 North Dr,Bldg 33,Rm 2E19A-2, Bethesda, MD 20892 USA.
EM piersontc@mail.nih.gov
FU Division of Intramural Research, National Institute of Allergy and
Infectious Diseases, National Institutes of Health; Vaccine Research
Center, National Institute of Allergy and Infectious Diseases, National
Institutes of Health
FX This work was supported by the intramural research programs of the
Division of Intramural Research and the Vaccine Research Center,
National Institute of Allergy and Infectious Diseases, National
Institutes of Health.
NR 15
TC 1
Z9 1
U1 1
U2 1
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0022-1899
EI 1537-6613
J9 J INFECT DIS
JI J. Infect. Dis.
PD NOV 15
PY 2016
VL 214
IS 10
BP 1487
EP 1491
DI 10.1093/infdis/jiw431
PG 5
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA ED0ZR
UT WOS:000388573700006
PM 27655868
ER
PT J
AU Yu, YW
Hsieh, TH
Chen, KY
Wu, JCC
Hoffer, BJ
Greig, NH
Li, YZ
Lai, JH
Chang, CF
Lin, JW
Chen, YH
Yang, LY
Chiang, YH
AF Yu, Yu-Wen
Hsieh, Tsung-Hsun
Chen, Kai-Yun
Wu, John Chung-Che
Hoffer, Barry J.
Greig, Nigel H.
Li, Yazhou
Lai, Jing-Huei
Chang, Cheng-Fu
Lin, Jia-Wei
Chen, Yu-Hsin
Yang, Liang-Yo
Chiang, Yung-Hsiao
TI Glucose-Dependent Insulinotropic Polypeptide Ameliorates Mild Traumatic
Brain Injury-Induced Cognitive and Sensorimotor Deficits and
Neuroinflammation in Rats
SO JOURNAL OF NEUROTRAUMA
LA English
DT Article
DE amyloid-beta precursor protein; BMX; cognitive dysfunction; controlled
cortical impact; GFAP; glucagon-like peptide-1; glucose-dependent
insulinotropic polypeptide; mild traumatic brain injury;
neuroinflammation
ID GLUCAGON-LIKE PEPTIDE-1; GASTRIC-INHIBITORY POLYPEPTIDE;
CENTRAL-NERVOUS-SYSTEM; CLOSED HEAD-INJURY; ALZHEIMERS-DISEASE;
GENE-EXPRESSION; NEURODEGENERATIVE DISEASE; SYNAPTIC PLASTICITY;
DIABETES-MELLITUS; SIGNALING PATHWAY
AB Mild traumatic brain injury (mTBI) is a major public health issue, representing 75-90% of all cases of TBI. In clinical settings, mTBI, which is defined as a Glascow Coma Scale (GCS) score of 13-15, can lead to various physical, cognitive, emotional, and psychological-related symptoms. To date, there are no pharmaceutical-based therapies to manage the development of the pathological deficits associated with mTBI. In this study, the neurotrophic and neuroprotective properties of glucose-dependent insulinotropic polypeptide (GIP), an incretin similar to glucagon-like peptide-1 (GLP-1), was investigated after its steady-state subcutaneous administration, focusing on behavior after mTBI in an in vivo animal model. The mTBI rat model was generated by a mild controlled cortical impact (mCCI) and used to evaluate the therapeutic potential of GIP. We used the Morris water maze and novel object recognition tests, which are tasks for spatial and recognition memory, respectively, to identify the putative therapeutic effects of GIP on cognitive function. Further, beam walking and the adhesive removal tests were used to evaluate locomotor activity and somatosensory functions in rats with and without GIP administration after mCCI lesion. Lastly, we used immunohistochemical (IHC) staining and Western blot analyses to evaluate the inflammatory markers, glial fibrillary acidic protein (GFAP), amyloid-beta precursor protein (APP), and bone marrow tyrosine kinase gene in chromosome X (BMX) in animals with mTBI. GIP was well tolerated and ameliorated mTBI-induced memory impairments, poor balance, and sensorimotor deficits after initiation in the post-injury period. In addition, GIP mitigated mTBI-induced neuroinflammatory changes on GFAP, APP, and BMX protein levels. These findings suggest GIP has significant benefits in managing mTBI-related symptoms and represents a novel strategy for mTBI treatment.
C1 [Yu, Yu-Wen; Hsieh, Tsung-Hsun; Chen, Kai-Yun; Hoffer, Barry J.; Chiang, Yung-Hsiao] Taipei Med Univ, Coll Med Sci & Technol, PhD Program Neural Regenerat Med, Taipei, Taiwan.
[Yu, Yu-Wen; Hsieh, Tsung-Hsun; Chen, Kai-Yun; Hoffer, Barry J.; Chiang, Yung-Hsiao] Natl Hlth Res Inst, Taipei, Taiwan.
[Hsieh, Tsung-Hsun; Chen, Kai-Yun; Lai, Jing-Huei; Chiang, Yung-Hsiao] Taipei Med Univ, Ctr Neurotrauma & Neuroregenerat, Taipei, Taiwan.
[Hsieh, Tsung-Hsun] Chang Gung Univ, Coll Med, Dept Phys Therapy, Taoyuan, Taiwan.
[Hsieh, Tsung-Hsun] Chang Gung Univ, Coll Med, Grad Inst Rehabil Sci, Taoyuan, Taiwan.
[Wu, John Chung-Che; Lai, Jing-Huei; Chang, Cheng-Fu; Lin, Jia-Wei; Chiang, Yung-Hsiao] Taipei Med Univ, Coll Med, Dept Surg, Taipei, Taiwan.
[Hoffer, Barry J.] Case Western Reserve Univ, Sch Med, Dept Neurosurg, Cleveland, OH USA.
[Greig, Nigel H.; Li, Yazhou] NIA, Drug Design & Dev Sect, Translat Gerontol Branch, Intramural Res Program,NIH, Baltimore, MD 21224 USA.
[Chen, Yu-Hsin; Yang, Liang-Yo] Taipei Med Univ, Sch Med, Dept Physiol, Coll Med, Taipei, Taiwan.
[Chen, Yu-Hsin] Taipei Med Univ, Coll Med, Grad Inst Med Sci, Taipei, Taiwan.
[Yang, Liang-Yo] Taipei Med Univ, Res Ctr Biomed Devices & Prototyping Prod, Taipei, Taiwan.
[Chiang, Yung-Hsiao] Taipei Med Univ Hosp, Dept Med Res, Translat Lab, Taipei, Taiwan.
[Yang, Liang-Yo] China Med Univ, Sch Med, Coll Med, Taichung, Taiwan.
RP Yang, LY (reprint author), China Med Univ, Sch Med, Coll Med, Taichung, Taiwan.; Chiang, YH (reprint author), Taipei Med Univ, Coll Med Sci & Technol, Grad Inst Neural Regenerat Med, 250 Wu Hsing St, Taipei 11031, Taiwan.
EM ychiang@tmu.edu.tw
FU Ministry of Science and Technology [MOST 103-2321-B-038-003, NSC
101-2321-B-038-004, NSC 102-2321-B-038-004, NSC 101-2632-B-038-001-MY3,
MOST 103-2314-B-038-038]; National Institute on Aging
FX This study was supported by the Ministry of Science and Technology,
grant number MOST 103-2321-B-038-003, NSC 101-2321-B-038-004, NSC
102-2321-B-038-004 and NSC 101-2632-B-038-001-MY3, MOST
103-2314-B-038-038 and the Intramural Research Program of the National
Institute on Aging.
NR 107
TC 3
Z9 3
U1 4
U2 4
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 0897-7151
EI 1557-9042
J9 J NEUROTRAUM
JI J. Neurotrauma
PD NOV 15
PY 2016
VL 33
IS 22
BP 2044
EP 2054
DI 10.1089/neu.2015.4229
PG 11
WC Critical Care Medicine; Clinical Neurology; Neurosciences
SC General & Internal Medicine; Neurosciences & Neurology
GA EC4OL
UT WOS:000388112300008
PM 26972789
ER
PT J
AU Green, AD
Vasu, S
McClenaghan, NH
Flatt, PR
AF Green, Alastair D.
Vasu, Srividya
McClenaghan, Neville H.
Flatt, Peter R.
TI Implanting 1.1B4 human beta-cell pseudoislets improves glycaemic control
in diabetic severe combined immune deficient mice
SO WORLD JOURNAL OF DIABETES
LA English
DT Article
DE Human beta-cell line; 1.1B4; Cell therapy; Insulin; Pseudoislets
ID CLINICAL ISLET TRANSPLANTATION; INDUCIBLE INSULIN-SECRETION;
FUNCTIONAL-CHARACTERIZATION; B-CELLS; LINE; PANCREAS; GLUCOSE;
EXPANSION; RESPONSES; MELLITUS
AB AIM
To investigate the potential of implanting pseudoislets formed from human insulin-releasing beta-cell lines as an alternative to islet transplantation.
METHODS
In this study, the anti-diabetic potential of novel human insulin releasing 1.1B4 beta-cells was evaluated by implanting the cells, either as free cell suspensions, or as three-dimensional pseudoislets, into the subscapular region of severe combined immune deficient mice rendered diabetic by single high-dose administration of streptozotocin. Metabolic parameters including food and fluid intake, bodyweight and blood glucose were monitored throughout the study. At the end of the study animals were given an intraperitoneal glucose tolerance test. Animals were then culled and blood and tissues were collected for analysis. Insulin and glucagon contents of plasma and tissues were measured by insulin radioimmunoassay and chemiluminescent enzyme-linked immunosorbance assay respectively. Histological analyses of pancreatic islets were carried out by quantitative fluorescence immunohistochemistry staining.
RESULTS
Both pseudoislet and cell suspension implants yielded well vascularised beta-cell masses of similar insulin content. This was associated with progressive amelioration of hyperphagia ( P < 0.05), polydipsia ( P < 0.05), body weight loss ( P < 0.05), hypoinsulinaemia ( P < 0.05), hyperglycaemia ( P < 0.05 - P < 0.001) and glucose tolerance ( P < 0.01). Islet morphology was also significantly improved in both groups of transplanted mice, with increased beta-cell ( P < 0.05 - P < 0.001) and decreased alpha cell ( P < 0.05 - P < 0.001) areas. Whereas mice receiving 1.1B4 cell suspensions eventually exhibited hypoglycaemic complications, pseudoislet recipients displayed a more gradual amelioration of diabetes, and achieved stable blood glucose control similar to non-diabetic mice at the end of the study.
CONCLUSION
Although further work is needed to address safety issues, these results provide proof of concept for possible therapeutic applicability of human beta-cell line pseudoislets in diabetes.
C1 [Green, Alastair D.; McClenaghan, Neville H.; Flatt, Peter R.] Univ Ulster, SAAD Ctr Pharm & Diabet, Coleraine BT52 1SA, Londonderry, North Ireland.
[Vasu, Srividya] NIDDK, Cell Growth & Metab Sect, NIH, Old Georgetown Rd & Ctr Dr, Bethesda, MD 20892 USA.
RP Vasu, S (reprint author), NIDDK, Cell Growth & Metab Sect, NIH, Old Georgetown Rd & Ctr Dr, Bethesda, MD 20892 USA.
EM s.vasu@outlook.com
NR 53
TC 0
Z9 0
U1 0
U2 0
PU BAISHIDENG PUBLISHING GROUP INC
PI PLEASANTON
PA 8226 REGENCY DR, PLEASANTON, CA 94588 USA
SN 1948-9358
J9 WORLD J DIABETES
JI World J. Diabetes
PD NOV 15
PY 2016
VL 7
IS 19
BP 523
EP 533
DI 10.4239/wjd.v7.i19.523
PG 11
WC Medicine, General & Internal
SC General & Internal Medicine
GA EC8BU
UT WOS:000388365900003
PM 27895821
ER
PT J
AU McNeely, J
Wu, LT
Subramaniam, G
Sharma, G
Cathers, LA
Svikis, D
Sleiter, L
Russell, L
Nordeck, C
Sharma, A
O'Grady, KE
Bouk, LB
Cushing, C
King, J
Wahle, A
Schwartz, RP
AF McNeely, Jennifer
Wu, Li-Tzy
Subramaniam, Geetha
Sharma, Gaurav
Cathers, Lauretta A.
Svikis, Dace
Sleiter, Luke
Russell, Linnea
Nordeck, Courtney
Sharma, Anjalee
O'Grady, Kevin E.
Bouk, Leah B.
Cushing, Carol
King, Jacqueline
Wahle, Aimee
Schwartz, Robert P.
TI Performance of the Tobacco, Alcohol, Prescription Medication, and Other
Substance Use (TAPS) Tool for Substance Use Screening in Primary Care
Patients
SO ANNALS OF INTERNAL MEDICINE
LA English
DT Article
ID BEHAVIORAL-COUNSELING INTERVENTIONS; DISORDERS IDENTIFICATION TEST;
LONGITUDINAL DATA-ANALYSIS; POSITIVE PREVALENCE RATES; RANDOMIZED
CLINICAL-TRIAL; SERVICES-TASK-FORCE; DRUG-USE; TEST ASSIST;
PREVENTIVE-SERVICES; SELF-REPORTS
AB Background: Substance use, a leading cause of illness and death, is underidentified in medical practice.
Objective: The Tobacco, Alcohol, Prescription medication, and other Substance use (TAPS) tool was developed to address the need for a brief screening and assessment instrument that includes all commonly used substances and fits into clinical work-flows. The goal of this study was to assess the performance of the TAPS tool in primary care patients.
Design: Multisite study, conducted within the National Drug Abuse Treatment Clinical Trials Network, comparing the TAPS tool with a reference standard measure. (ClinicalTrials.gov: NCT02110693)
Setting: 5 adult primary care clinics.
Participants: 2000 adult patients consecutively recruited from clinic waiting areas.
Measurements: Interviewer-and self-administered versions of the TAPS tool were compared with a reference standard, the modified World Mental Health Composite International Diagnostic Interview (CIDI), which measures problem use and substance use disorder (SUD).
Results: Interviewer-and self-administered versions of the TAPS tool had similar diagnostic characteristics. For identifying problem use (at a cutoff of 1+), the TAPS tool had a sensitivity of 0.93 (95% CI, 0.90 to 0.95) and specificity of 0.87 (CI, 0.85 to 0.89) for tobacco and a sensitivity of 0.74 (CI, 0.70 to 0.78) and specificity of 0.79 (CI, 0.76 to 0.81) for alcohol. For problem use of illicit and prescription drugs, sensitivity ranged from 0.82 (CI, 0.76 to 0.87) for marijuana to 0.63 (CI, 0.47 to 0.78) for sedatives; specificity was 0.93 or higher. For identifying any SUD (at a cutoff of 2+), sensitivity was lower.
Limitations: The low prevalence of some drug classes led to poor precision in some estimates. Research assistants were not blinded to participants' TAPS tool responses when they administered the CIDI.
Conclusion: In a diverse population of adult primary care patients, the TAPS tool detected clinically relevant problem substance use. Although it also may detect tobacco, alcohol, and marijuana use disorders, further refinement is needed before it can be recommended broadly for SUD screening.
C1 [McNeely, Jennifer] NYU, Sch Med, Dept Populat Hlth, 550 First Ave,VZ30 6th Floor, New York, NY 10016 USA.
[McNeely, Jennifer] Dept Med, Div Gen Internal Med, 550 First Ave,VZ30 6th Floor, New York, NY 10016 USA.
[Wu, Li-Tzy] Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Dept Med, Durham, NC 27710 USA.
[Wu, Li-Tzy] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC 27710 USA.
[Subramaniam, Geetha; Cushing, Carol] NIDA, Ctr Clin Trials Network, NIH, 6001 Execut Blvd, Bethesda, MD 20892 USA.
[Sharma, Anjalee; King, Jacqueline; Wahle, Aimee] EMMES Corp, 401 North Washington St, Rockville, MD 20850 USA.
[Cathers, Lauretta A.] Virginia Commonwealth Univ, 730 East Broad St,Room 3076, Richmond, VA 23298 USA.
[Svikis, Dace] Virginia Commonwealth Univ, POB 98034,1001 East Broad St,Room 305, Richmond, VA 23298 USA.
[Sleiter, Luke; Russell, Linnea] NYU, Sch Med, 227 East 30th St,7th Floor, New York, NY 10016 USA.
[Nordeck, Courtney; Sharma, Anjalee; Schwartz, Robert P.] Friends Res Inst, 1040 Pk Ave,Suite 103, Baltimore, MD 21201 USA.
[O'Grady, Kevin E.] Univ Maryland, College Pk, MD 20742 USA.
[Bouk, Leah B.] Duke Univ, Sch Med, Duke Translat Res Inst, Kannapolis, NC USA.
RP McNeely, J (reprint author), NYU, Sch Med, Dept Populat Hlth, 550 First Ave,VZ30 6th Floor, New York, NY 10016 USA.
EM Jennifer.McNeely@nyumc.org
OI McNeely, Jennifer/0000-0003-4601-6940
FU National Institute on Drug Abuse
FX National Institute on Drug Abuse.
NR 70
TC 0
Z9 0
U1 3
U2 3
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 NOV 15
PY 2016
VL 165
IS 10
BP 690
EP +
DI 10.7326/M16-0317
PG 14
WC Medicine, General & Internal
SC General & Internal Medicine
GA EC2RB
UT WOS:000387970500013
PM 27595276
ER
PT J
AU Gamaldo, AA
Beydoun, MA
Beydoun, HA
Liang, HL
Sales, RE
Zonderman, AB
Gamaldo, CE
Eid, SM
AF Gamaldo, Alyssa A.
Beydoun, May A.
Beydoun, Hind A.
Liang, Hailun
Sales, Rachel E.
Zonderman, Alan B.
Gamaldo, Charlene E.
Eid, Shaker M.
TI Sleep Disturbances among Older Adults in the United States, 2002-2012:
Nationwide Inpatient Rates, Predictors, and Outcomes
SO FRONTIERS IN AGING NEUROSCIENCE
LA English
DT Article
DE sleep disturbances; sleep disorders; inpatient sample; co-morbidity;
length of stay; health care cost; mortality; older adults
ID ALL-CAUSE MORTALITY; INSOMNIA-RELATED SYMPTOMS; AFRICAN-AMERICANS;
FOLLOW-UP; APNEA; DURATION; COHORT; RISK; POPULATION; HEALTH
AB Objective/Background: We examined the rates, predictors, and outcomes [mortality risk (MR), length of stay (LOS), and total charges (TC)] of sleep disturbances in older hospitalized patients.
Patients/Methods: Using the U.S. Nationwide Inpatient Sample database (2002-2012), older patients (>= 60 years) were selected and rates of insomnia, obstructive sleep apnea (OSA) and other sleep disturbances (OSD) were estimated using ICD-9CM. TC, adjusted for inflation, was of primary interest, while MR and LOS were secondary outcomes. Multivariable regression analyses were conducted.
Results: Of 35,258,031 older adults, 263,865 (0.75%) had insomnia, 750,851 (2.13%) OSA and 21,814 (0.06%) OSD. Insomnia rates increased significantly (0.27% in 2002 to 1.29 in 2012, P-trend < 0.001), with a similar trend observed for OSA (1.47 in 2006 to 5.01 in 2012, P-trend < 0.001). TC (2012 $) for insomnia-related hospital admission increased over time from $22,250 in 2002 to $31,527 in 2012, and increased similarly for OSA and OSD; while LOS and MR both decreased. Women with any sleep disturbance had lower MR and TC than men, while Whites had consistently higher odds of insomnia, OSA, and OSD than older Blacks and Hispanics. Co-morbidities such as depression, cardiovascular risk factors, and neurological disorders steadily increased over time in patients with sleep disturbances.
Conclusion: TC increased over time in patients with sleep disturbances while LOS and MR decreased. Further, research should focus on identifying the mechanisms that explain the association between increasing sleep disturbance rates and expenditures within hospital settings and the potential hospital expenditures of unrecognized sleep disturbances in the elderly.
C1 [Gamaldo, Alyssa A.] Univ S Florida, Sch Aging Studies, Tampa, FL USA.
[Gamaldo, Alyssa A.; Beydoun, May A.; Zonderman, Alan B.] NIA, Behav Epidemiol Sect, Lab Epidemiol & Populat Sci, NIH,IRP, Baltimore, MD 21224 USA.
[Gamaldo, Alyssa A.] Penn State Univ, Human Dev & Family Studies, State Coll, PA USA.
[Beydoun, Hind A.] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA.
[Liang, Hailun] Johns Hopkins Univ, Dept Hlth Policy & Management, Sch Publ Hlth, Baltimore, MD 21218 USA.
[Sales, Rachel E.; Gamaldo, Charlene E.] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA.
RP Beydoun, MA (reprint author), NIA, Behav Epidemiol Sect, Lab Epidemiol & Populat Sci, NIH,IRP, Baltimore, MD 21224 USA.
EM baydounm@mail.nih.gov
FU NIA/NIH/IRP
FX This study was supported in part by the NIA/NIH/IRP in collaboration
with Johns Hopkins University School of Medicine. We would like to thank
Ms. Danielle Shaked and Dr. Greg Dore for their internal review of the
manuscript.
NR 66
TC 0
Z9 0
U1 4
U2 4
PU FRONTIERS MEDIA SA
PI LAUSANNE
PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015,
SWITZERLAND
SN 1663-4365
J9 FRONT AGING NEUROSCI
JI Front. Aging Neurosci.
PD NOV 15
PY 2016
VL 8
AR 266
DI 10.3339/fnagi.2016.00266
PG 14
WC Geriatrics & Gerontology; Neurosciences
SC Geriatrics & Gerontology; Neurosciences & Neurology
GA EB9OI
UT WOS:000387724500001
PM 27895576
ER
PT J
AU Bibbins-Domingo, K
Grossman, DC
Curry, SJ
Davidson, K
Epling, JW
Garcia, FAR
Gillman, MW
Kemper, AR
Krist, AH
Kurth, AE
Landefeld, CS
LeFevre, ML
Mangione, CM
Phillips, WR
Owens, DK
Phipps, MG
Pignone, MP
AF Bibbins-Domingo, Kirsten
Grossman, David C.
Curry, Susan J.
Davidson, KarinaW.
Epling, John W., Jr.
Garcia, Francisco A. R.
Gillman, Matthew W.
Kemper, Alex R.
Krist, Alex H.
Kurth, Ann E.
Landefeld, C. Seth
LeFevre, Michael L.
Mangione, Carol M.
Phillips, William R.
Owens, Douglas K.
Phipps, Maureen G.
Pignone, Michael P.
CA US Preventive Serv Task Force
TI Statin Use for the Primary Prevention of Cardiovascular Disease in
Adults US Preventive Services Task Force Recommendation Statement
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Review
ID CORONARY-HEART-DISEASE; C-REACTIVE PROTEIN; WOMENS HEALTH; RISK;
CHOLESTEROL; EVENTS; COHORT; INTERVENTIONS; DYSLIPIDEMIA; GUIDELINES
AB IMPORTANCE Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in the United States, accounting for 1 of every 3 deaths among adults.
OBJECTIVE To update the 2008 US Preventive Services Task Force (USPSTF) recommendation on screening for lipid disorders in adults.
EVIDENCE REVIEW The USPSTF reviewed the evidence on the benefits and harms of screening for and treatment of dyslipidemia in adults 21 years and older; the benefits and harms of statin use in reducing CVD events and mortality in adults without a history of CVD events; whether the benefits of statin use vary by subgroup, clinical characteristics, or dosage; and the benefits of various treatment strategies in adults 40 years and older without a history of CVD events.
CONCLUSIONS AND RECOMMENDATIONS The USPSTF recommends initiating use of low-to moderate-dose statins in adults aged 40 to 75 years without a history of CVD who have 1 or more CVD risk factors (dyslipidemia, diabetes, hypertension, or smoking) and a calculated 10-year CVD event risk of 10% or greater (B recommendation). The USPSTF recommends that clinicians selectively offer low-to moderate-dose statins to adults aged 40 to 75 years without a history of CVD who have 1 or more CVD risk factors and a calculated 10-year CVD event risk of 7.5% to 10% (C recommendation). The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of initiating statin use in adults 76 years and older (I statement).
C1 [Bibbins-Domingo, Kirsten] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Grossman, David C.] Grp Hlth Res Inst, Seattle, WA USA.
[Curry, Susan J.] Univ Iowa, Iowa City, IA USA.
[Davidson, KarinaW.] Columbia Univ, New York, NY USA.
[Epling, John W., Jr.] SUNY Upstate Med Univ, Syracuse, NY 13210 USA.
[Garcia, Francisco A. R.] Pima Cty Dept Hlth, Tucson, AZ USA.
[Gillman, Matthew W.] Harvard Med Sch, Boston, MA USA.
[Gillman, Matthew W.] Harvard Pilgrim Hlth Care Inst, Boston, MA USA.
[Gillman, Matthew W.] NIH, Bldg 10, Bethesda, MD 20892 USA.
[Kemper, Alex R.] Duke Univ, Durham, NC USA.
[Krist, Alex H.] Fairfax Family Practice Residency, Fairfax, VA USA.
[Krist, Alex H.] Virginia Commonwealth Univ, Richmond, VA 23284 USA.
[Kurth, Ann E.] Yale Univ, New Haven, CT USA.
[Landefeld, C. Seth] Univ Alabama Birmingham, Birmingham, AL USA.
[LeFevre, Michael L.] Univ Missouri, Columbia, MO 65211 USA.
[Mangione, Carol M.] Univ Calif Los Angeles, Los Angeles, CA USA.
[Phillips, William R.] Univ Washington, Seattle, WA 98195 USA.
[Owens, Douglas K.] Stanford Univ, Stanford, CA 94305 USA.
[Phipps, Maureen G.] Brown Univ, Providence, RI 02912 USA.
[Pignone, Michael P.] Univ Texas Austin, Austin, TX 78712 USA.
RP Bibbins-Domingo, K (reprint author), Univ Calif San Francisco, San Francisco, CA 94143 USA.
EM chair@uspstf.net
FU USPSTF
FX The USPSTF is an independent, voluntary body. The US Congress mandates
that the Agency for Healthcare Research and Quality (AHRQ) support the
operations of the USPSTF.
NR 44
TC 9
Z9 9
U1 5
U2 5
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 0098-7484
EI 1538-3598
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD NOV 15
PY 2016
VL 316
IS 19
BP 1997
EP 2007
DI 10.1001/jama.2016.15450
PG 11
WC Medicine, General & Internal
SC General & Internal Medicine
GA EB8XC
UT WOS:000387673800018
ER
PT J
AU Dobbin, KK
Cesano, A
Alvarez, J
Hawtin, R
Janetzki, S
Kirsch, I
Masucci, GV
Robbins, PB
Selvan, SR
Streicher, HZ
Zhang, J
Butterfield, LH
Thurin, M
AF Dobbin, Kevin K.
Cesano, Alessandra
Alvarez, John
Hawtin, Rachael
Janetzki, Sylvia
Kirsch, Ilan
Masucci, Giuseppe V.
Robbins, Paul B.
Selvan, Senthamil R.
Streicher, Howard Z.
Zhang, Jenny
Butterfield, Lisa H.
Thurin, Magdalena
TI Validation of biomarkers to predict response to immunotherapy in cancer:
Volume II - clinical validation and regulatory considerations
SO JOURNAL FOR IMMUNOTHERAPY OF CANCER
LA English
DT Review
DE Biomarker; Immunotherapy; Cancer; Assay; Validation; Regulatory
ID CELL LUNG-CANCER; COMPANION DIAGNOSTICS; CHEMOTHERAPY; EXPRESSION;
TRIALS
AB There is growing recognition that immunotherapy is likely to significantly improve health outcomes for cancer patients in the coming years. Currently, while a subset of patients experience substantial clinical benefit in response to different immunotherapeutic approaches, the majority of patients do not but are still exposed to the significant drug toxicities. Therefore, a growing need for the development and clinical use of predictive biomarkers exists in the field of cancer immunotherapy. Predictive cancer biomarkers can be used to identify the patients who are or who are not likely to derive benefit from specific therapeutic approaches. In order to be applicable in a clinical setting, predictive biomarkers must be carefully shepherded through a step-wise, highly regulated developmental process. Volume I of this two-volume document focused on the pre-analytical and analytical phases of the biomarker development process, by providing background, examples and "good practice" recommendations. In the current Volume II, the focus is on the clinical validation, validation of clinical utility and regulatory considerations for biomarker development. Together, this two volume series is meant to provide guidance on the entire biomarker development process, with a particular focus on the unique aspects of developing immune-based biomarkers. Specifically, knowledge about the challenges to clinical validation of predictive biomarkers, which has been gained from numerous successes and failures in other contexts, will be reviewed together with statistical methodological issues related to bias and overfitting. The different trial designs used for the clinical validation of biomarkers will also be discussed, as the selection of clinical metrics and endpoints becomes critical to establish the clinical utility of the biomarker during the clinical validation phase of the biomarker development. Finally, the regulatory aspects of submission of biomarker assays to the U.S. Food and Drug Administration as well as regulatory considerations in the European Union will be covered.
C1 [Dobbin, Kevin K.] Univ Georgia, Coll Publ Hlth, Dept Epidemiol & Biostat, 101 Buck Rd, Athens, GA 30602 USA.
[Cesano, Alessandra] NanoString Inc, 530 Fairview Ave N, Seattle, WA 98109 USA.
[Alvarez, John] Janssen Res & Dev LLC, Spring House, PA 19477 USA.
[Hawtin, Rachael] Nodality Inc, 170 Harbor Way, San Francisco, CA 94080 USA.
[Janetzki, Sylvia] ZellNet Consulting Inc, 555 North Ave, Ft Lee, NJ 07024 USA.
[Kirsch, Ilan] Adapt Biotechnol Inc, 1551 Eastlake Ave E, Seattle, WA 98102 USA.
[Masucci, Giuseppe V.] Karolinska Inst, Dept Oncol Pathol, S-17176 Stockholm, Sweden.
[Robbins, Paul B.] Pfizer, San Diego, CA USA.
[Selvan, Senthamil R.] Omni Array Biotechnol, 15601 Crabbs Branch Way, Rockville, MD 20855 USA.
[Streicher, Howard Z.] NCI, NIH, 9609 Med Ctr Dr, Bethesda, MD 20892 USA.
[Zhang, Jenny] Covaris Inc, 14 Gill St, Woburn, MA 01801 USA.
[Butterfield, Lisa H.] Univ Pittsburgh, Inst Canc, Dept Med Surg & Immunol, 5117 Ctr Ave, Pittsburgh, PA 15213 USA.
[Thurin, Magdalena] NCI, Canc Diag Program, DCTD, NIH, 9609 Med Ctr Dr, Bethesda, MD 20892 USA.
RP Thurin, M (reprint author), NCI, Canc Diag Program, DCTD, NIH, 9609 Med Ctr Dr, Bethesda, MD 20892 USA.
EM thurinm@mail.nih.gov
NR 36
TC 2
Z9 2
U1 3
U2 3
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 2051-1426
J9 J IMMUNOTHER CANCER
JI J. Immunother. Cancer
PD NOV 15
PY 2016
VL 4
AR 77
DI 10.1186/s40425-016-0179-0
PG 14
WC Oncology
SC Oncology
GA EC3RL
UT WOS:000388043200003
PM 27891226
ER
PT J
AU Masucci, GV
Cesano, A
Hawtin, R
Janetzki, S
Zhang, J
Kirsch, I
Dobbin, KK
Alvarez, J
Robbins, PB
Selvan, SR
Streicher, HZ
Butterfield, LH
Thurin, M
AF Masucci, Giuseppe V.
Cesano, Alessandra
Hawtin, Rachael
Janetzki, Sylvia
Zhang, Jenny
Kirsch, Ilan
Dobbin, Kevin K.
Alvarez, John
Robbins, Paul B.
Selvan, Senthamil R.
Streicher, Howard Z.
Butterfield, Lisa H.
Thurin, Magdalena
TI Validation of biomarkers to predict response to immunotherapy in cancer:
Volume I - pre-analytical and analytical validation
SO JOURNAL FOR IMMUNOTHERAPY OF CANCER
LA English
DT Review
DE Biomarker; Immunotherapy; Cancer; Assay; Validation; Standardization
ID TUMOR-INFILTRATING LYMPHOCYTES; ASSAYS PRACTICE GUIDELINES; ADVANCED
MELANOMA PATIENTS; RESISTANT PROSTATE-CANCER; PARAFFIN-EMBEDDED TISSUE;
GENE-EXPRESSION ANALYSIS; BLOOD MONONUCLEAR-CELLS; ACUTE
MYELOID-LEUKEMIA; PD-1 BLOCKADE; METASTATIC MELANOMA
AB Immunotherapies have emerged as one of the most promising approaches to treat patients with cancer. Recently, there have been many clinical successes using checkpoint receptor blockade, including T cell inhibitory receptors such as cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and programmed cell death-1 (PD-1). Despite demonstrated successes in a variety of malignancies, responses only typically occur in a minority of patients in any given histology. Additionally, treatment is associated with inflammatory toxicity and high cost. Therefore, determining which patients would derive clinical benefit from immunotherapy is a compelling clinical question. Although numerous candidate biomarkers have been described, there are currently three FDA-approved assays based on PD-1 ligand expression (PD-L1) that have been clinically validated to identify patients who are more likely to benefit from a single-agent anti-PD-1/PD-L1 therapy. Because of the complexity of the immune response and tumor biology, it is unlikely that a single biomarker will be sufficient to predict clinical outcomes in response to immune-targeted therapy. Rather, the integration of multiple tumor and immune response parameters, such as protein expression, genomics, and transcriptomics, may be necessary for accurate prediction of clinical benefit. Before a candidate biomarker and/or new technology can be used in a clinical setting, several steps are necessary to demonstrate its clinical validity. Although regulatory guidelines provide general roadmaps for the validation process, their applicability to biomarkers in the cancer immunotherapy field is somewhat limited. Thus, Working Group 1 (WG1) of the Society for Immunotherapy of Cancer (SITC) Immune Biomarkers Task Force convened to address this need. In this two volume series, we discuss pre-analytical and analytical (Volume I) as well as clinical and regulatory (Volume II) aspects of the validation process as applied to predictive biomarkers for cancer immunotherapy. To illustrate the requirements for validation, we discuss examples of biomarker assays that have shown preliminary evidence of an association with clinical benefit from immunotherapeutic interventions. The scope includes only those assays and technologies that have established a certain level of validation for clinical use (fit-for-purpose). Recommendations to meet challenges and strategies to guide the choice of analytical and clinical validation design for specific assays are also provided.
C1 [Masucci, Giuseppe V.] Karolinska Inst, Dept Oncol Pathol, S-17176 Stockholm, Sweden.
[Cesano, Alessandra] NanoString Inc, 500 Fairview Ave North, Seattle, WA 98109 USA.
[Hawtin, Rachael] Nodality Inc, 170 Harbor Way, San Francisco, CA 94080 USA.
[Janetzki, Sylvia] ZellNet Consulting Inc, 555 North Ave, Ft Lee, NJ 07024 USA.
[Zhang, Jenny] Covaris Inc, 14 Gill St, Woburn, MA 01801 USA.
[Kirsch, Ilan; Thurin, Magdalena] Adapt Biotechnol Inc, 1551 Eastlake Ave E, Seattle, WA 98102 USA.
[Dobbin, Kevin K.] Univ Georgia, Coll Publ Hlth, Dept Epidemiol & Biostat, 101 Buck Rd, Athens, GA 30602 USA.
[Alvarez, John] Janssen Res & Dev LLC, Spring House, PA 19477 USA.
[Robbins, Paul B.] Pfizer, San Diego, CA USA.
[Selvan, Senthamil R.] Omni Array Biotechnol, 15601 Crabbs Branch Way, Rockville, MD 20855 USA.
[Streicher, Howard Z.] NCI, NIH, 9609 Med Ctr Dr, Bethesda, MD 20892 USA.
[Butterfield, Lisa H.] Univ Pittsburgh, Dept Med Surg & Immunol, Inst Canc, 5117 Ctr Ave, Pittsburgh, PA 15213 USA.
[Thurin, Magdalena] NCI, Canc Diag Program, DCTD, NIH, 9609 Med Ctr Dr, Bethesda, MD 20892 USA.
RP Thurin, M (reprint author), Adapt Biotechnol Inc, 1551 Eastlake Ave E, Seattle, WA 98102 USA.; Thurin, M (reprint author), NCI, Canc Diag Program, DCTD, NIH, 9609 Med Ctr Dr, Bethesda, MD 20892 USA.
EM thurinm@mail.nih.gov
NR 177
TC 2
Z9 2
U1 8
U2 8
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 2051-1426
J9 J IMMUNOTHER CANCER
JI J. Immunother. Cancer
PD NOV 15
PY 2016
VL 4
AR 76
DI 10.1186/s40425-016-0178-1
PG 25
WC Oncology
SC Oncology
GA EC3RL
UT WOS:000388043200002
PM 27895917
ER
PT J
AU Ascierto, PA
Agarwala, S
Botti, G
Cesano, A
Ciliberto, G
Davies, MA
Demaria, S
Dummer, R
Eggermont, AM
Ferrone, S
Fu, YX
Gajewski, TF
Garbe, C
Huber, V
Khleif, S
Krauthammer, M
Lo, RS
Masucci, G
Palmieri, G
Postow, M
Puzanov, I
Silk, A
Spranger, S
Stroncek, DF
Tarhini, A
Taube, JM
Testori, A
Wang, E
Wargo, JA
Yee, C
Zarour, H
Zitvogel, L
Fox, BA
Mozzillo, N
Marincola, FM
Thurin, M
AF Ascierto, Paolo A.
Agarwala, Sanjiv
Botti, Gerardo
Cesano, Alessandra
Ciliberto, Gennaro
Davies, Michael A.
Demaria, Sandra
Dummer, Reinhard
Eggermont, Alexander M.
Ferrone, Soldano
Fu, Yang Xin
Gajewski, Thomas F.
Garbe, Claus
Huber, Veronica
Khleif, Samir
Krauthammer, Michael
Lo, Roger S.
Masucci, Giuseppe
Palmieri, Giuseppe
Postow, Michael
Puzanov, Igor
Silk, Ann
Spranger, Stefani
Stroncek, David F.
Tarhini, Ahmad
Taube, Janis M.
Testori, Alessandro
Wang, Ena
Wargo, Jennifer A.
Yee, Cassian
Zarour, Hassane
Zitvogel, Laurence
Fox, Bernard A.
Mozzillo, Nicola
Marincola, Francesco M.
Thurin, Magdalena
TI Future perspectives in melanoma research
SO JOURNAL OF TRANSLATIONAL MEDICINE
LA English
DT Article
ID HERPES-SIMPLEX-VIRUS; STAGE-III MELANOMA; CD8(+) T-CELLS; METASTATIC
MELANOMA; UNTREATED MELANOMA; ADJUVANT THERAPY; TUMOR MICROENVIRONMENT;
ANTITUMOR IMMUNITY; BRAF INHIBITION; CTLA-4 BLOCKADE
AB The sixth "Melanoma Bridge Meeting" took place in Naples, Italy, December 1st-4th, 2015. The four sessions at this meeting were focused on: (1) molecular and immune advances; (2) combination therapies; (3) news in immunotherapy; and 4) tumor microenvironment and biomarkers. Recent advances in tumor biology and immunology has led to the development of new targeted and immunotherapeutic agents that prolong progression-free survival (PFS) and overall survival (OS) of cancer patients. Immunotherapies in particular have emerged as highly successful approaches to treat patients with cancer including melanoma, non-small cell lung cancer (NSCLC), renal cell carcinoma (RCC), bladder cancer, and Hodgkin's disease. Specifically, many clinical successes have been using checkpoint receptor blockade, including T cell inhibitory receptors such as cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and the programmed cell death-1 (PD-1) and its ligand PD-L1. Despite demonstrated successes, responses to immunotherapy interventions occur only in a minority of patients. Attempts are being made to improve responses to immunotherapy by developing biomarkers. Optimizing biomarkers for immunotherapy could help properly select patients for treatment and help to monitor response, progression and resistance that are critical challenges for the immuno-oncology (IO) field. Importantly, biomarkers could help to design rational combination therapies. In addition, biomarkers may help to define mechanism of action of different agents, dose selection and to sequence drug combinations. However, biomarkers and assays development to guide cancer immunotherapy is highly challenging for several reasons: (i) multiplicity of immunotherapy agents with different mechanisms of action including immunotherapies that target activating and inhibitory T cell receptors (e.g., CTLA-4, PD-1, etc.); adoptive T cell therapies that include tissue infiltrating lymphocytes (TILs), chimeric antigen receptors (CARs), and T cell receptor (TCR) modified T cells; (ii) tumor heterogeneity including changes in antigenic profiles over time and location in individual patient; and (iii) a variety of immune-suppressive mechanisms in the tumor microenvironment (TME) including T regulatory cells (Treg), myeloid derived suppressor cells (MDSC) and immunosuppressive cytokines. In addition, complex interaction of tumor-immune system further increases the level of difficulties in the process of biomarkers development and their validation for clinical use. Recent clinical trial results have highlighted the potential for combination therapies that include immunomodulating agents such as anti-PD-1 and anti-CTLA-4. Agents targeting other immune inhibitory (e.g., Tim-3) or immune stimulating (e.g., CD137) receptors on T cells and other approaches such as adoptive cell transfer are tested for clinical efficacy in melanoma as well. These agents are also being tested in combination with targeted therapies to improve upon shorter-term responses thus far seen with targeted therapy. Various locoregional interventions that demonstrate promising results in treatment of advanced melanoma are also integrated with immunotherapy agents and the combinations with cytotoxic chemotherapy and inhibitors of angiogenesis are changing the evolving landscape of therapeutic options and are being evaluated to prevent or delay resistance and to further improve survival rates for melanoma patients' population. This meeting's specific focus was on advances in immunotherapy and combination therapy for melanoma.
The importance of understanding of melanoma genomic background for development of novel therapies and biomarkers for clinical application to predict the treatment response was an integral part of the meeting. The overall emphasis on biomarkers supports novel concepts toward integrating biomarkers into personalized-medicine approach for treatment of patients with melanoma across the entire spectrum of disease stage. Translation of the knowledge gained from the biology of tumor microenvironment across different tumors represents a bridge to impact on prognosis and response to therapy in melanoma. We also discussed the requirements for pre-analytical and analytical as well as clinical validation process as applied to biomarkers for cancer immunotherapy. The concept of the fit-for-purpose marker validation has been introduced to address the challenges and strategies for analytical and clinical validation design for specific assays.
C1 [Ascierto, Paolo A.; Botti, Gerardo; Ciliberto, Gennaro; Mozzillo, Nicola] Fdn G Pascale, IRCCS Ist Nazl Tumori, Naples, Italy.
[Agarwala, Sanjiv] St Lukes Univ Hosp, Dept Hematol & Oncol, Bethlehem, PA USA.
[Agarwala, Sanjiv] Temple Univ, Bethlehem, PA USA.
[Cesano, Alessandra] Nanostring Inc, 500 Fairview Ave N, Seattle, WA 98109 USA.
[Davies, Michael A.] Univ Texas MD Anderson Canc Ctr, Div Canc Med, Dept Melanoma Med Oncol, Houston, TX 77030 USA.
[Demaria, Sandra] Weill Cornell Med Coll, Dept Radiat Oncol, New York, NY USA.
[Demaria, Sandra] Weill Cornell Med Coll, Dept Pathol, New York, NY USA.
[Dummer, Reinhard] Univ Hosp Zurich, Skin Canc Unit, Dept Dermatol, CH-8091 Zurich, Switzerland.
[Eggermont, Alexander M.] Gustave Roussy Canc Campus Grand Paris, Villejuif, France.
[Ferrone, Soldano] Harvard Med Sch, Massachusetts Gen Hosp, Dept Surg, Boston, MA USA.
[Fu, Yang Xin] UT Southwestern Med Ctr, Dept Pathol, Dallas, TX USA.
[Gajewski, Thomas F.] Univ Chicago Med, Dept Med, Immunol & Canc Program, Chicago, IL USA.
[Gajewski, Thomas F.] Univ Chicago Med, Dept Pathol, Immunol & Canc Program, Chicago, IL USA.
[Garbe, Claus] Univ Tubingen, Dept Dermatol, Ctr Dermato Oncol, Tubingen, Germany.
[Huber, Veronica] Fdn IRCCS Ist Nazl Tumori, Milan, Italy.
[Khleif, Samir] Georgia Regents Univ, Ctr Canc, Augusta, GA USA.
[Krauthammer, Michael] Yale Univ, Sch Med, New Haven, CT USA.
[Lo, Roger S.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA.
[Lo, Roger S.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Mol & Med Pharmacol, Los Angeles, CA 90095 USA.
[Lo, Roger S.] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90024 USA.
[Masucci, Giuseppe] Karolinska Inst, Dept Oncol Pathol, Stockholm, Sweden.
[Palmieri, Giuseppe] CNR, Inst Biomol Chem, Unit Canc Genet, Sassari, Italy.
[Postow, Michael] Mem Sloan Kettering Canc Ctr, Dept Med, 1275 York Ave, New York, NY 10021 USA.
[Postow, Michael] Weill Cornell Med Coll, New York, NY USA.
[Puzanov, Igor] Roswell Pk Canc Inst, Dept Med, Early Phase Clin Trials Program, New York, NY USA.
[Silk, Ann] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA.
[Spranger, Stefani] Univ Chicago, Chicago, IL 60637 USA.
[Stroncek, David F.] NIH, Cell Proc Sect, Dept Transfus Med, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA.
[Tarhini, Ahmad; Zarour, Hassane] Univ Pittsburgh, Dept Med, Pittsburgh, PA USA.
[Tarhini, Ahmad; Zarour, Hassane] Univ Pittsburgh, Dept Immunol, Pittsburgh, PA USA.
[Tarhini, Ahmad; Zarour, Hassane] Univ Pittsburgh, Dept Dermatol, Pittsburgh, PA 15260 USA.
[Taube, Janis M.] Johns Hopkins Univ SOM, Dept Dermatol, Baltimore, MD USA.
[Testori, Alessandro] Ist Europeo Oncol, Milan, Italy.
[Wang, Ena] Sidra Med & Res Ctr, Div Translat Med, Doha, Qatar.
[Wargo, Jennifer A.] Univ Texas MD Anderson Canc Ctr, Genom Med & Surg Oncol, Houston, TX 77030 USA.
[Yee, Cassian; Marincola, Francesco M.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Zitvogel, Laurence] Gustave Roussy Canc Ctr, INSERM, U1015, Villejuif, France.
[Zitvogel, Laurence] Univ Paris 11, Le Kremlin Bicetre, France.
[Fox, Bernard A.] Providence Portland Med Ctr, Robert W Franz Canc Res Ctr, Earle A Chiles Res Inst, Providence Canc Ctr, Portland, OR USA.
[Fox, Bernard A.] Oregon Hlth & Sci Univ, Dept Mol Microbiol & Immunol, Portland, OR 97201 USA.
[Thurin, Magdalena] NCI, Canc Diag Program, NIH, Bethesda, MD 20892 USA.
[Ascierto, Paolo A.] Fdn G Pascale, Unit Med Oncol & Innovat Therapy, Ist Nazl Studio & Cura Tumori, Via Mariano Semmola, I-80131 Naples, Italy.
RP Thurin, M (reprint author), NCI, Canc Diag Program, NIH, Bethesda, MD 20892 USA.; Ascierto, PA (reprint author), Fdn G Pascale, Unit Med Oncol & Innovat Therapy, Ist Nazl Studio & Cura Tumori, Via Mariano Semmola, I-80131 Naples, Italy.
EM paolo.ascierto@gmail.com; thurinm@mail.nih.gov
FU Fondazione Melanoma Onlus; Society of ImmunoTherapy of Cancer (SITC); 3P
Solution of Napoli
FX The meeting was supported by Fondazione Melanoma Onlus and the Society
of ImmunoTherapy of Cancer (SITC). A special thanks to 3P Solution of
Napoli for their support and cooperation in organizing the meeting and
especially to Lucia Politi.
NR 145
TC 0
Z9 0
U1 26
U2 26
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 NOV 15
PY 2016
VL 14
AR 313
DI 10.1186/s12967-016-1070-y
PG 25
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA EB9QX
UT WOS:000387732200001
PM 27846884
ER
PT J
AU Chen, G
Shin, YW
Taylor, PA
Glen, DR
Reynolds, RC
Israel, RB
Cox, RW
AF Chen, Gang
Shin, Yong-Wook
Taylor, Paul A.
Glen, Daniel R.
Reynolds, Richard C.
Israel, Robert B.
Cox, Robert W.
TI Untangling the relatedness among correlations, part I: Nonparametric
approaches to inter-subject correlation analysis at the group level
SO NEUROIMAGE
LA English
DT Article
ID HUMAN BRAIN; INTERSUBJECT CORRELATIONS; HEMODYNAMIC-RESPONSE;
PERMUTATION TESTS; FMRI; CORTEX; SYNCHRONIZATION; SOFTWARE; SYSTEMS;
REVEAL
AB FMRI data acquisition under naturalistic and continuous stimuli (e.g., watching a video or listening to music) has become popular recently due to the fact that it entails less manipulation and more realistic/complex contexts involved in the task, compared to the conventional task-based experimental designs. The synchronization or response similarities among subjects are typically measured through inter-subject correlation (ISC) between any pair of subjects. At the group level, summarizing the collection of ISC values is complicated by their intercorrelations, which necessarily lead to the violation of independence assumed in typical parametric approaches such as Student's t-test. Nonparametric methods, such as bootstrapping and permutation testing, have previously been adopted for testing purposes by resampling the time series of each subject, but the quantitative validity of these specific approaches in terms of controllability of false positive rate (FPR) has never been explored before. Here we survey the methods of ISC group analysis that have been employed in the literature, and discuss the issues involved in those methods. We then propose less computationally intensive nonparametric methods that can be performed at the group level (for both one-and two-sample analyses), as compared to the popular method of circularly shifting the EPI time series at the individual level. As part of the new approaches, subject-wise (SW) resampling is adopted instead of element-wise (EW) resampling, so that exchangeability and independence assumptions are satisfied, and the patterned correlation structure among the ISC values can be more accurately captured. We examine the FPR controllability and power achievement of all the methods through simulations, as well as their performance when applied to a real experimental dataset. Published by Elsevier Inc.
C1 [Chen, Gang; Taylor, Paul A.; Glen, Daniel R.; Reynolds, Richard C.; Cox, Robert W.] NIMH, Sci & Stat Comp Core, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Shin, Yong-Wook] Univ Ulsan, Coll Med, Dept Psychiat, Asan Med Ctr, Ulsan, South Korea.
[Israel, Robert B.] Univ British Columbia, Dept Math, Vancouver, BC V5Z 1M9, Canada.
RP Chen, G (reprint author), NIMH, Sci & Stat Comp Core, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.; Shin, YW (reprint author), Univ Ulsan, Coll Med, Dept Psychiat, Asan Med Ctr, Ulsan, South Korea.
EM gangchen@mail.nih.gov; shaman_korea@mac.com
OI Chen, Gang/0000-0002-2960-089X
FU NIMH Program of the NIH/HHS, USA [1ZICMH002888]; NINDS Intramural
Research Program of the NIH/HHS, USA [1ZICMH002888]; Asan Institute for
Life Sciences, Asan Medical Center, Seoul, Korea [2012-0230]
FX Our work benefited significantly from the statistical computational
language and environment R, its many packages, and the great support of
the R community. All the plots were created in R with the base graphics
library. We gratefully acknowledge the advice of J.-P. Kauppi, J. Tohka,
and J. Pajula for using the ISC Toolbox. The research and writing of the
paper were supported by the NIMH and NINDS Intramural Research Programs
(1ZICMH002888) of the NIH/HHS, USA, and by a grant (2012-0230) from the
Asan Institute for Life Sciences, Asan Medical Center, Seoul, Korea.
This work utilized the computational resources of the NIH HPC Biowulf
cluster (http://hpc.nih.gov).
NR 49
TC 1
Z9 1
U1 1
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
EI 1095-9572
J9 NEUROIMAGE
JI Neuroimage
PD NOV 15
PY 2016
VL 142
BP 238
EP 249
DI 10.1016/j.neuroimage.2016.05.023
PG 12
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA EC2WW
UT WOS:000387986000020
PM 27195792
ER
PT J
AU Liu, JJ
Loncar, I
Collee, JM
Bolla, MK
Dennis, J
Michailidou, K
Wang, Q
Andrulis, IL
Barile, M
Beckmann, MW
Behrens, S
Benitez, J
Blomqvist, C
Boeckx, B
Bogdanova, NV
Bojesen, SE
Brauch, H
Brennan, P
Brenner, H
Broeks, A
Burwinkel, B
Chang-Claude, J
Chen, ST
Chenevix-Trench, G
Cheng, CY
Choi, JY
Couch, FJ
Cox, A
Cross, SS
Cuk, K
Czene, K
Dork, T
Dos-Santos-Silva, I
Fasching, PA
Figueroa, J
Flyger, H
Garcia-Closas, M
Giles, GG
Glendon, G
Goldberg, MS
Gonzalez-Neira, A
Guenel, P
Haiman, CA
Hamann, U
Hart, SN
Hartman, M
Hatse, S
Hopper, JL
Ito, H
Jakubowska, A
Kabisch, M
Kang, D
Kosma, VM
Kristensen, VN
Le Marchand, L
Lee, E
Li, JM
Lophatananon, A
Lubinski, J
Mannermaa, A
Matsuo, K
Milne, RL
Neuhausen, SL
Nevanlinna, H
Orr, N
Perez, JIA
Peto, J
Putti, TC
Pylkas, K
Radice, P
Sangrajrang, S
Sawyer, EJ
Schmidt, MK
Schneeweiss, A
Shen, CY
Shrubsole, MJ
Shu, XO
Simard, J
Southey, MC
Swerdlow, A
Teo, SH
Tessier, DC
Thanasitthichai, S
Tomlinson, I
Torres, D
Truong, T
Tseng, CC
Vachon, C
Winqvist, R
Wu, AH
Yannoukakos, D
Zheng, W
Hall, P
Dunning, AM
Easton, DF
Hooning, MJ
van den Ouweland, AMW
Martens, JWM
Hollestelle, A
AF Liu, Jingjing
Loncar, Ivona
Collee, J. Margriet
Bolla, Manjeet K.
Dennis, Joe
Michailidou, Kyriaki
Wang, Qin
Andrulis, Irene L.
Barile, Monica
Beckmann, Matthias W.
Behrens, Sabine
Benitez, Javier
Blomqvist, Carl
Boeckx, Bram
Bogdanova, Natalia V.
Bojesen, Stig E.
Brauch, Hiltrud
Brennan, Paul
Brenner, Hermann
Broeks, Annegien
Burwinkel, Barbara
Chang-Claude, Jenny
Chen, Shou-Tung
Chenevix-Trench, Georgia
Cheng, Ching Y.
Choi, Ji-Yeob
Couch, Fergus J.
Cox, Angela
Cross, Simon S.
Cuk, Katarina
Czene, Kamila
Doerk, Thilo
Dos-Santos-Silva, Isabel
Fasching, Peter A.
Figueroa, Jonine
Flyger, Henrik
Garcia-Closas, Montserrat
Giles, Graham G.
Glendon, Gord
Goldberg, Mark S.
Gonzalez-Neira, Anna
Guenel, Pascal
Haiman, Christopher A.
Hamann, Ute
Hart, Steven N.
Hartman, Mikael
Hatse, Sigrid
Hopper, John L.
Ito, Hidemi
Jakubowska, Anna
Kabisch, Maria
Kang, Daehee
Kosma, Veli-Matti
Kristensen, Vessela N.
Le Marchand, Loic
Lee, Eunjung
Li, Jingmei
Lophatananon, Artitaya
Lubinski, Jan
Mannermaa, Arto
Matsuo, Keitaro
Milne, Roger L.
Neuhausen, Susan L.
Nevanlinna, Heli
Orr, Nick
Perez, Jose I. A.
Peto, Julian
Putti, Thomas C.
Pylkas, Katri
Radice, Paolo
Sangrajrang, Suleeporn
Sawyer, Elinor J.
Schmidt, Marjanka K.
Schneeweiss, Andreas
Shen, Chen-Yang
Shrubsole, Martha J.
Shu, Xiao-Ou
Simard, Jacques
Southey, Melissa C.
Swerdlow, Anthony
Teo, Soo H.
Tessier, Daniel C.
Thanasitthichai, Somchai
Tomlinson, Ian
Torres, Diana
Truong, Therese
Tseng, Chiu-Chen
Vachon, Celine
Winqvist, Robert
Wu, Anna H.
Yannoukakos, Drakoulis
Zheng, Wei
Hall, Per
Dunning, Alison M.
Easton, Douglas F.
Hooning, Maartje J.
van den Ouweland, Ans M. W.
Martens, John W. M.
Hollestelle, Antoinette
CA NBCS Collaborators
TI rs2735383, located at a microRNA binding site in the 3 ' UTR of NBS1, is
not associated with breast cancer risk
SO SCIENTIFIC REPORTS
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; DOUBLE-STRAND BREAKS; GLU185GLN POLYMORPHISM;
FUNCTIONAL POLYMORPHISM; PATHWAY GENES; LUNG-CANCER; METAANALYSIS;
SUSCEPTIBILITY; REPAIR; POPULATIONS
AB NBS1, also known as NBN, plays an important role in maintaining genomic stability. Interestingly, rs2735383 G > C, located in a microRNA binding site in the 3'-untranslated region (UTR) of NBS1, was shown to be associated with increased susceptibility to lung and colorectal cancer. However, the relation between rs2735383 and susceptibility to breast cancer is not yet clear. Therefore, we genotyped rs2735383 in 1,170 familial non-BRCA1/2 breast cancer cases and 1,077 controls using PCR-based restriction fragment length polymorphism (RFLP-PCR) analysis, but found no association between rs2735383CC and breast cancer risk (OR = 1.214, 95% CI = 0.936-1.574, P = 0.144). Because we could not exclude a small effect size due to a limited sample size, we further analyzed imputed rs2735383 genotypes (r(2) > 0.999) of 47,640 breast cancer cases and 46,656 controls from the Breast Cancer Association Consortium (BCAC). However, rs2735383CC was not associated with overall breast cancer risk in European (OR = 1.014, 95% CI = 0.969-1.060, P = 0.556) nor in Asian women (OR = 0.998, 95% CI = 0.905-1.100, P = 0.961). Subgroup analyses by age, age at menarche, age at menopause, menopausal status, number of pregnancies, breast feeding, family history and receptor status also did not reveal a significant association. This study therefore does not support the involvement of the genotype at NBS1 rs2735383 in breast cancer susceptibility.
C1 [Liu, Jingjing; Loncar, Ivona; Hooning, Maartje J.; Martens, John W. M.; Hollestelle, Antoinette] Erasmus MC Canc Inst, Dept Med Oncol, Family Canc Clin, Rotterdam, Netherlands.
[Collee, J. Margriet; van den Ouweland, Ans M. W.] Erasmus Univ, Dept Clin Genet, Med Ctr, Rotterdam, Netherlands.
[Bolla, Manjeet K.; Dennis, Joe; Michailidou, Kyriaki; Wang, Qin; Easton, Douglas F.] Univ Cambridge, Dept Publ Hlth & Primary Care, Ctr Canc Genet Epidemiol, Cambridge, England.
[Michailidou, Kyriaki] Cyprus Inst Neurol & Genet, Dept Electron Microscopy Mol Pathol, Nicosia, Cyprus.
[Andrulis, Irene L.; Glendon, Gord] Mt Sinai Hosp, Fred A Litwin Ctr Canc Genet, Lunenfeld Tanenbaum Res Inst, Toronto, ON, Canada.
[Andrulis, Irene L.] Univ Toronto, Dept Mol Genet, Toronto, ON, Canada.
[Barile, Monica] Ist Europeo Oncol, Div Canc Prevent & Genet, Milan, Italy.
[Beckmann, Matthias W.; Fasching, Peter A.] Univ Erlangen Nurnberg, Univ Hosp Erlangen, Dept Gynaecol & Obstet, Comprehens Canc Ctr Erlangen EMN, Erlangen, Germany.
[Behrens, Sabine; Chang-Claude, Jenny] German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany.
[Behrens, Sabine; Chang-Claude, Jenny] Univ Med Ctr Hamburg Eppendorf, Univ Canc Ctr Hamburg, Hamburg, Germany.
[Benitez, Javier; Gonzalez-Neira, Anna] Spanish Natl Canc Res Ctr, Human Canc Genet Program, Madrid, Spain.
[Benitez, Javier] Ctr Invest Red Enfermedades Raras CIBERER, Valencia, Spain.
[Blomqvist, Carl] Univ Helsinki, Helsinki Univ Hosp, Dept Oncol, Helsinki, Finland.
[Boeckx, Bram] VIB, Res Ctr, Leuven, Belgium.
[Boeckx, Bram] Univ Leuven, Dept Oncol, Lab Translat Genet, Leuven, Belgium.
[Bogdanova, Natalia V.] Hannover Med Sch, Dept Radiat Oncol, Hannover, Germany.
[Bogdanova, Natalia V.; Doerk, Thilo] Hannover Med Sch, Gynaecol Res Unit, Hannover, Germany.
[Bogdanova, Natalia V.] NN Alexandrov Res Inst Oncol & Med Radiol, Minsk, Byelarus.
[Bojesen, Stig E.] Copenhagen Univ Hosp, Herlev & Gentofte Hosp, Copenhagen Gen Populat Study, Herlev, Denmark.
[Bojesen, Stig E.] Copenhagen Univ Hosp, Herlev & Gentofte Hosp, Dept Clin Biochem, Herlev, Denmark.
[Bojesen, Stig E.] Univ Copenhagen, Fac Hlth & Med Sci, Copenhagen, Denmark.
[Brauch, Hiltrud] Dr Margarete Fischer Bosch Inst Clin Pharmacol, Stuttgart, Germany.
[Brauch, Hiltrud] Univ Tubingen, Tubingen, Germany.
[Brauch, Hiltrud; Brenner, Hermann] German Canc Res Ctr, German Canc Consortium DKTK, Heidelberg, Germany.
[Brennan, Paul] Int Agcy Res Canc, Lyon, France.
[Brenner, Hermann; Cuk, Katarina] German Canc Res Ctr, Div Clin Epidemiol & Aging Res, Heidelberg, Germany.
[Brenner, Hermann] German Canc Res Ctr, Div Prevent Oncol, Heidelberg, Germany.
[Brenner, Hermann] Natl Ctr Tumor Dis NCT, Heidelberg, Germany.
[Broeks, Annegien; Schmidt, Marjanka K.] Antoni van Leeuwenhoek Hosp, Netherlands Canc Inst, Div Mol Pathol, Amsterdam, Netherlands.
[Burwinkel, Barbara; Schneeweiss, Andreas] Heidelberg Univ, Dept Obstet & Gynecol, Heidelberg, Germany.
[Burwinkel, Barbara] German Canc Res Ctr, Mol Epidemiol Grp, C080, Heidelberg, Germany.
[Chen, Shou-Tung] Changhua Christian Hosp, Dept Surg, Changhua, Taiwan.
[Chenevix-Trench, Georgia] QIMR Berghofer Med Res Inst, Dept Genet & Computat Biol, Brisbane, Qld, Australia.
[Cheng, Ching Y.] Singapore Eye Res Inst, Singapore, Singapore.
[Cheng, Ching Y.] Singapore Natl Eye Ctr, Singapore, Singapore.
[Cheng, Ching Y.] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Ophthalmol, Singapore, Singapore.
[Cheng, Ching Y.] Natl Univ Hlth Syst, Singapore, Singapore.
[Cheng, Ching Y.] Duke NUS Grad Med Sch, Singapore, Singapore.
[Choi, Ji-Yeob; Kang, Daehee] Seoul Natl Univ, Coll Med, Dept Biol Sci, Seoul, South Korea.
[Choi, Ji-Yeob; Kang, Daehee] Seoul Natl Univ, Canc Res Inst, Seoul, South Korea.
[Couch, Fergus J.] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA.
[Cox, Angela] Univ Sheffield, Dept Oncol & Metab, Acad Unit Mol Oncol, Sheffield, S Yorkshire, England.
[Cross, Simon S.] Univ Sheffield, Dept Neurosci, Acad Unit Pathol, Sheffield, S Yorkshire, England.
[Czene, Kamila; Li, Jingmei; Hall, Per] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
[Dos-Santos-Silva, Isabel; Peto, Julian] London Sch Hyg & Trop Med, Dept Noncommunicable Dis Epidemiol, London, England.
[Fasching, Peter A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Hematol & Oncol, Los Angeles, CA 90095 USA.
[Figueroa, Jonine] Univ Edinburgh, Sch Med, Usher Inst Populat Hlth Sci & Informat, Edinburgh, Midlothian, Scotland.
[Figueroa, Jonine; Garcia-Closas, Montserrat] NCI, Div Canc Epidemiol & Genet, Rockville, MD USA.
[Flyger, Henrik] Copenhagen Univ Hosp, Herlev & Gentofte Hosp, Dept Breast Surg, Herlev, Denmark.
[Giles, Graham G.; Milne, Roger L.] Canc Council Victoria, Canc Epidemiol Ctr, Melbourne, Vic, Australia.
[Giles, Graham G.; Hopper, John L.; Milne, Roger L.] Univ Melbourne, Melbourne Sch Populat & Global Hlth, Ctr Epidemiol & Biostat, Melbourne, Vic, Australia.
[Goldberg, Mark S.] McGill Univ, Dept Med, Montreal, PQ, Canada.
[Goldberg, Mark S.] McGill Univ, Royal Victoria Hosp, Div Clin Epidemiol, Montreal, PQ, Canada.
[Guenel, Pascal; Truong, Therese] Univ Paris Saclay, Univ Paris Sud, INSERM, Canc & Environm Grp,Ctr Res Epidemiol & Populat H, Villejuif, France.
[Haiman, Christopher A.; Lee, Eunjung; Tseng, Chiu-Chen; Wu, Anna H.] Univ Southern Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA USA.
[Hamann, Ute; Kabisch, Maria; Torres, Diana] German Canc Res Ctr, Mol Genet Breast Canc, Heidelberg, Germany.
[Hart, Steven N.; Vachon, Celine] Mayo Clin, Dept Hlth Sci Res, Rochester, MN USA.
[Hartman, Mikael] Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore.
[Hartman, Mikael] Natl Univ Hlth Syst, Dept Surg, Singapore, Singapore.
[Hatse, Sigrid] Univ Hosp Leuven, Leuven Canc Inst, Dept Oncol, Leuven Multidisciplinary Breast Ctr, Leuven, Belgium.
[Ito, Hidemi] Aichi Canc Ctr, Div Epidemiol & Prevent, Res Inst, Nagoya, Aichi, Japan.
[Ito, Hidemi; Matsuo, Keitaro] Nagoya Univ, Grad Sch Med, Dept Epidemiol, Nagoya, Aichi, Japan.
[Jakubowska, Anna; Lubinski, Jan] Pomeranian Med Univ, Dept Genet & Pathol, Szczecin, Poland.
[Kang, Daehee] Seoul Natl Univ, Coll Med, Dept Prevent Med, Seoul, South Korea.
[Kosma, Veli-Matti; Mannermaa, Arto] Univ Eastern Finland, Translat Canc Res Area, Kuopio, Finland.
[Kosma, Veli-Matti; Mannermaa, Arto] Univ Eastern Finland, Inst Clin Med Pathol & Forens Med, Kuopio, Finland.
[Kosma, Veli-Matti; Mannermaa, Arto] Kuopio Univ Hosp, Dept Clin Pathol, Imaging Ctr, Kuopio, Finland.
[Kristensen, Vessela N.] Radiumhospitalet, Oslo Univ Hosp, Inst Canc Res, Dept Canc Genet, Oslo, Norway.
[Kristensen, Vessela N.] Oslo Univ Hosp, Univ Oslo, Dept Clin Mol Biol, Oslo, Norway.
[Le Marchand, Loic] Univ Hawaii, Ctr Canc, Epidemiol Program, Honolulu, HI 96822 USA.
[Lophatananon, Artitaya] Univ Warwick, Warwick Med Sch, Div Hlth Sci, Coventry, W Midlands, England.
[Lophatananon, Artitaya] Univ Manchester, Inst Populat Hlth, Manchester, Lancs, England.
[Matsuo, Keitaro] Aichi Canc Ctr, Res Inst, Div Mol Med, Nagoya, Aichi, Japan.
[Neuhausen, Susan L.] City Hope Natl Med Ctr, Beckman Res Inst, Dept Populat Sci, Duarte, CA USA.
[Nevanlinna, Heli] Univ Helsinki, Helsinki Univ Hosp, Dept Obstet & Gynecol, Helsinki, Finland.
[Orr, Nick; Swerdlow, Anthony] Inst Canc Res, Div Breast Canc Res, London, England.
[Perez, Jose I. A.] Hosp Monte Naranco, Serv Cirugia Gen & Especialidades, Oviedo, Spain.
[Putti, Thomas C.] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Pathol, Singapore, Singapore.
[Pylkas, Katri; Winqvist, Robert] Univ Oulu, Bioctr Oulu, Canc & Translat Med Res Unit, Lab Canc Genet & Tumor Biol, Oulu, Finland.
[Pylkas, Katri; Winqvist, Robert] Northern Finland Lab Ctr NordLab, Lab Canc Genet & Tumor Biol, Oulu, Finland.
[Radice, Paolo] Fdn IRCCS Ist Ricovero & Cura Carattere Sci, INT, Dept Prevent & Predict Med, Unit Mol Bases Genet Risk & Genet Testing, Milan, Italy.
[Sangrajrang, Suleeporn] Natl Canc Inst, Bangkok, Thailand.
[Sawyer, Elinor J.] Kings Coll London, Guys Hosp, Res Oncol, London, England.
[Schmidt, Marjanka K.] Antoni van Leeuwenhoek Hosp, Netherlands Canc Inst, Div Psychosocial Res & Epidemiol, Amsterdam, Netherlands.
[Schneeweiss, Andreas] Heidelberg Univ, Natl Ctr Tumor Dis, Heidelberg, Germany.
[Shen, Chen-Yang] China Med Univ, Sch Publ Hlth, Taichung, Taiwan.
[Shen, Chen-Yang] Acad Sinica, Taiwan Biobank, Inst Biomed Sci, Taipei, Taiwan.
[Shrubsole, Martha J.; Shu, Xiao-Ou; Zheng, Wei] Vanderbilt Univ, Sch Med, Vanderbilt Ingram Canc Ctr, Div Epidemiol,Dept Med,Vanderbilt Epidemiol Ctr, Nashville, TN 37212 USA.
[Simard, Jacques] Univ Laval, Res Ctr, Ctr Hosp Univ Quebec, Genom Ctr, Quebec City, PQ, Canada.
[Southey, Melissa C.] Univ Melbourne, Dept Pathol, Genet Epidemiol Lab, Melbourne, Vic, Australia.
[Swerdlow, Anthony] Inst Canc Res, Div Genet & Epidemiol, London, England.
[Teo, Soo H.] Canc Res Malaysia, Subang Jaya, Selangor, Malaysia.
[Teo, Soo H.] Univ Malaya, Med Ctr, Canc Res Inst, Breast Canc Res Unit, Kuala Lumpur, Malaysia.
[Tessier, Daniel C.] McGill Univ, Montreal, PQ, Canada.
[Tessier, Daniel C.] Genome Quebec Innovat Ctr, Montreal, PQ, Canada.
[Thanasitthichai, Somchai] Natl Canc Inst, Res & Technol Assessment Dept, Bangkok, Thailand.
[Tomlinson, Ian] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.
[Tomlinson, Ian] Univ Oxford, Oxford NIHR Biomed Res Ctr, Oxford, England.
[Torres, Diana] Pontificia Univ Javeriana, Inst Human Genet, Bogota, Colombia.
[Yannoukakos, Drakoulis] Natl Ctr Sci Res Demokritos, INRASTES, Mol Diagnost Lab, Athens, Greece.
[Dunning, Alison M.; Easton, Douglas F.] Univ Cambridge, Dept Oncol, Ctr Canc Genet Epidemiol, Cambridge, England.
[Martens, John W. M.] Canc Genom Netherlands, Utrecht, Netherlands.
RP Hollestelle, A (reprint author), Erasmus MC Canc Inst, Dept Med Oncol, Family Canc Clin, Rotterdam, Netherlands.
EM a.hollestelle@erasmusmc.nl
RI Li, Jingmei/I-2904-2012; Brenner, Hermann/B-4627-2017; Dork,
Thilo/J-8620-2012
OI Li, Jingmei/0000-0001-8587-7511; Brenner, Hermann/0000-0002-6129-1572;
FU Department Director-General of Disease Control; NHMRC; National Breast
Cancer Foundation; Cancer Australia; National Institute of Health (USA);
Breast Cancer Now; Institute of Cancer Research; NHS; Cancer Genomics
Netherlands (CGC.nl); grant for the Netherlands Organization of
Scientific Research (NWO); China Scholarship Council (Beijing, China);
Cancer Research UK [C1287/A12014, C1287/A10118, C1287/A 10710,
C12292/A11174, C1281/A12014, C5047/A8384, C5047/A15007, C5047/A10692,
C8197/A16565, C490/A10124]; European Community [223175,
HEALTH-F2-2009-223175]; National Institutes of Health [CA128978, R01
CA77398, UM1 CA164917, U01 CA199277]; Post-Cancer GWAS initiative [1U19
CA148537, 1U19 CA148065, 1U19 CA148112]; Department of Defence
[W81XWH-10-1-0341]; Canadian Institutes of Health Research (CIHR) for
the CIHR Team in Familial Risks of Breast Cancer; Komen Foundation for
the Cure; Breast Cancer Research Foundation; Ovarian Cancer Research
Fund; National Cancer Institute (USA) [UM1 CA164920]; National Health
and Medical Research Council of Australia; New South Wales Cancer
Council; Victorian Health Promotion Foundation (Australia); Victorian
Breast Cancer Research Consortium; Dutch Cancer Society [NKI 2007-3839,
2009 4363, DDHK 2004-3124, DDHK 2009-4318]; Breast Cancer Research
Trust, UK; ELAN-Fond of the University Hospital of Erlangen; Cancer
Research UK; National Cancer Research Network (NCRN); NIHR Comprehensive
Biomedical Research Centre, Guy's & St. Thomas' NHS Foundation Trust in
partnership with King's College London, United Kingdom; Oxford
Biomedical Research Centre; Dietmar-Hopp Foundation; Helmholtz Society;
German Cancer Research Center (DKFZ); Fondation de France; Institut
National du Cancer (INCa); Ligue Nationale contre le Cancer; Agence
Nationale de Securite Sanitaire; de l'Alimentation; de l'Environnement
et du Travail (ANSES); Agence Nationale de la Recherche (ANR); Chief
Physician Johan Boserup and Lise Boserup Fund; Danish Medical Research
Council; Herlev and Gentofte Hospital; Instituto de Salud Carlos III
(CEGEN); Fondo de Investigacion Sanitario [PI11/00923, PI12/00070];
FEDER funds; H2020 (BRIDGES project); California Breast Cancer Act;
California Breast Cancer Research Fund [97-10500]; California Department
of Public Health [103885]; Lon V Smith Foundation [LVS39420]; Baden
Wurttemberg Ministry of Science, Research and Arts; German Cancer Aid
(Deutsche Krebshilfe); Federal Ministry of Education and Research (BMBF)
Germany [01KW9975/5, 01KW9976/8, 01KW9977/0, 01KW0114, 01KH0402]; Robert
Bosch Foundation, Stuttgart; Deutsches Krebsforschungszentrum (DKFZ),
Heidelberg; Institute for Prevention and Occupational Medicine of the
German Social Accident Insurance, Institute of the Ruhr University
Bochum (IPA), Bochum; Department of Internal Medicine, Evangelische
Kliniken Bonn gGmbH, Johanniter Krankenhaus, Bonn, Germany; Helsinki
University Central Hospital Research Fund; Academy of Finland [266528,
250083, 122715, 251314]; Finnish Cancer Society; Nordic Cancer Union;
Sigrid Juselius Foundation; MEXT Kakenhi from the Ministry of Education,
Science, Sports, Culture and Technology of Japan [170150181, 26253041];
Ministry Health, Labour and Welfare of Japan; Health and Labour Sciences
Research Grants for Research on Applying Health Technology from Ministry
Health, Labour and Welfare of Japan; National Cancer Center Research and
Development Fund; "Practical Research for Innovative Cancer Control from
Japan Agency for Medical Research and development [15ck0106177h0001];
AMED; Cancer Bio Bank Aichi; Friends of Hannover Medical School; Rudolf
Bartling Foundation; Merit and Hans Rausings Initiative Against Breast
Cancer; special Government Funding (EVO) of Kuopio University Hospital
grants; Cancer Fund of North Savo; Finnish Cancer Organizations;
University of Eastern Finland; National Health and Medical Research
Council (NHMRC); Queensland Cancer Fund; Cancer Council of New South
Wales; Cancer Council of Victoria; Cancer Council of Tasmania; Cancer
Council of South Australia; Cancer Foundation of Western Australia;
United States Army Medical Research and Materiel Command
[DAMD17-01-1-0729]; Cancer Council Victoria; Cancer Council New South
Wales; Cancer Council South Australia; Cancer Council Tasmania; National
Health and Medical Research Council of Australia (NHMRC) [400413,
400281, 199600]; California Breast Cancer Research Program [1RB-0287,
3PB-0102, 5PB-0018, 10PB-0098]; California Department of Health;
National Cancer Institute's Division of Cancer Prevention and Control
Surveillance, Epidemiology, and End Results Program [N01CN25403];
'Stichting tegen Kanker'; FWO; Deutsche Krebshilfe e.V. [70-2892-BR I,
106332, 108253, 108419, 110826, 110828]; Hamburg Cancer Society; Italian
Association for Cancer Research (AIRC); Fondazione IRCCS Istituto
Nazionale Tumori; NIH [CA192393, CA116167, CA176785, CA63464, CA54281,
CA098758, CA132839, CA164973, R01CA100374, R01CA64277, R01CA148667,
UMCA182910, R37CA70867]; NIH Specialized Program of Research Excellence
(SPORE) in Breast Cancer [CA116201]; Australian NHMRC [209057, 251553,
504711]; Quebec Breast Cancer Foundation; Canadian Institutes of Health
Research for the " CIHR Team in Familial Risks of Breast Cancer" program
[CRN-87521]; Ministry of Economic Development, Innovation and Export
Trade [PSR-SIIRI-701]; Malaysian Ministry of Higher Education
[UM.C/HlR/MOHE/06, RP046B-15HTM]; Cancer Research Malaysia; Yayasan Sime
Darby LPGA Tournament; Research Council of Norway [193387/V50,
193387/H10]; South Eastern Norway Health Authority [39346, 27208];
Norwegian Cancer Society [419616-71248 -PR-2006-0282]; K. G. Jebsen
Centre for Breast Cancer Research; Finnish Cancer Foundation; University
of Oulu; University of Oulu Support Foundation; special Governmental EVO
funds for Oulu University Hospital-based research activities; Intramural
Research Funds of the National Cancer Institute, Department of Health
and Human Services, USA; Agency for Science, Technology and Research of
Singapore (A*STAR); US National Institute of Health (NIH); Susan G.
Komen Breast Cancer Foundation; Survey and Biospecimen Shared Resource
[P30 CA68485]; Genetic Associations and Mechanisms in Oncology (GAME-ON)
Network [U19 CA148065]; Sheffield Experimental Cancer Medicine Centre
and Breast Cancer Now; UK National Institute for Health Research
Biomedical Research Centre at the University of Cambridge; BRL (Basic
Research Laboratory) program through the National Research Foundation of
Korea - Ministry of Education, Science and Technology [2012-0000347];
NUS start-up Grant; National University Cancer Institute Singapore
(NCIS) Centre Grant; NMRC Clinician Scientist Award; Biomedical Research
Council [05/1/21/19/425]; DKFZ; National Cancer Institute Thailand;
Specialized Program of Research Excellence (SPORE) in Breast Cancer
[CA116201]; Hellenic Cooperative Oncology Group [HR R_BG/04]; Greek
General Secretary for Research and Technology (GSRT) Program, Research
Excellence II; European Union (European Social Fund - ESF); Greek
national funds through the Operational Program "Education and Lifelong
Learning" of the National Strategic Reference Framework (NSRF) -
ARISTEIA; Taiwan Biobank project of the Institute of Biomedical
Sciences, Academia Sinica, Taiwan; Institute of Cancer Research (ICR),
London; [PBZ_KBN_122/P05/2004]
FX We thank all the individuals who took part in these studies and all the
researchers, clinicians, technicians and administrative staff who have
enabled this work to be carried out. This study would not have been
possible without the contributions of the following: Paul Pharoah
(BCAC), Andrew Berchuck (OCAC), Rosalind A. Eeles, Ali Amin Al Olama,
Zsofia Kote-Jarai and Sara Benlloch (PRACTICAL), Antonis Antoniou,
Lesley McGuffog and Ken Offit (CIMBA), Andrew Lee, Ed Dicks, Craig
Luccarini and the staff of the Centre for Genetic Epidemiology
Laboratory, the staff of the CNIO genotyping unit, Francois Bacot,
Daniel Vincent, Sylvie La Boissiere and Frederic Robidoux and the staff
of the McGill University and Genome Quebec Innovation Centre, Sune F.
Nielsen, Borge G. Nordestgaard, and the staff of the Copenhagen DNA
laboratory, and Julie M. Cunningham, Sharon A. Windebank, Christopher A.
Hilker, Jeffrey Meyer and the staff of Mayo Clinic Genotyping Core
Facility; ABCFS: Maggie Angelakos, Judi Maskiell, Gillian Dite; ABCS:
Blood bank Sanquin (The Netherlands); ACP: The ACP study wishes to thank
the participants in the Thai Breast Cancer study. Special Thanks also go
to the Thai Ministry of Public Health (MOPH), doctors and nurses who
helped with the data collection process. Finally, the study would like
to thank Dr Prat Boonyawongviroj, the former Permanent Secretary of MOPH
and Dr Pornthep Siriwanarungsan, the Department Director-General of
Disease Control who have supported the study throughout; BBCS: Eileen
Williams, Elaine Ryder-Mills, Kara Sargus; BIGGS: Niall McInerney,
Gabrielle Colleran, Andrew Rowan, Angela Jones; BSUCH: Peter Bugert,
Medical Faculty Mannheim; CGPS: Staff and participants of the Copenhagen
General Population Study. For the excellent technical assistance: Dorthe
Uldall Andersen, Maria Birna Arnadottir, Anne Bank, Dorthe Kjeldgard
Hansen. The Danish Cancer Biobank is acknowledged for providing
infrastructure for the collection of blood samples for the cases;
CNIO-BCS: Guillermo Pita, Charo Alonso, Nuria Alvarez, Pilar Zamora,
Primitiva Menendez, the Human Genotyping-CEGEN Unit (CNIO); CTS: The CTS
Steering Committee includes Leslie Bernstein, Susan Neuhausen, James
Lacey, Sophia Wang, Huiyan Ma, and Jessica Clague DeHart at the Beckman
Research Institute of City of Hope, Dennis Deapen, Rich Pinder, and
Eunjung Lee at the University of Southern California, Pam Horn-Ross,
Peggy Reynolds, Christina Clarke Dur and David Nelson at the Cancer
Prevention Institute of California, Hoda Anton-Culver, Argyrios Ziogas,
and Hannah Park at the University of California Irvine, and Fred
Schumacher at Case Western University. Hartwig Ziegler, Sonja Wolf,
Volker Hermann, Christa Stegmaier, Katja Butterbach; GENICA: The GENICA
Network: Dr.; Margarete Fischer-Bosch-Institute of Clinical
Pharmacology, Stuttgart, and University of Tubingen, Germany [Hiltrud
Brauch, Wing-Yee Lo, Christina Justenhoven], German Cancer Consortium
(DKTK) and German Cancer Research Center (DKFZ) [Hiltrud Brauch],
Department of Internal Medicine, Evangelische Kliniken Bonn gGmbH,
Johanniter Krankenhaus, Bonn, Germany [Yon-Dschun Ko, Christian Baisch],
Institute of Pathology, University of Bonn, Germany [HansPeter Fischer],
Molecular Genetics of Breast Cancer, Deutsches Krebsforschungszentrum
(DKFZ), Heidelberg, Germany [Ute Hamann], Institute for Prevention and
Occupational Medicine of the German Social Accident Insurance, Institute
of the Ruhr University Bochum (IPA), Bochum, Germany [Thomas Bruning,
Beate Pesch, Sylvia Rabstein, Anne Lotz]; and Institute of Occupational
Medicine and Maritime Medicine, University Medical Center
Hamburg-Eppendorf, Germany [Volker Harth]; HEBCS: Kristiina Aittomaki,
Sofia Khan, Taru A. Muranen, Kirsimari Aaltonen, Karl von Smitten, Irja
Erkkila; HMBCS: Peter Hillemanns, Hans Christiansen and Johann H.
Karstens; pKARMA: The Swedish Medical Research Counsel; KBCP: Eija
Myohanen, Helena Kemilainen; kConFab/AOCS: We wish to thank Heather
Thorne, Eveline Niedermayr, all the kConFab research nurses and staff,
the heads and staff of the Family Cancer Clinics, and the Clinical
Follow Up Study (which has received funding from the NHMRC, the National
Breast Cancer Foundation, Cancer Australia, and the National Institute
of Health (USA)) for their contributions to this resource, and the many
families who contribute to kConFab; LAABC: We thank all the study
participants and the entire data collection team, especially Annie Fung
and June Yashiki; LMBC: Gilian Peuteman, Thomas Van Brussel,
EvyVanderheyden and Kathleen Corthouts; MARIE: Anja Rudolph, Petra
Seibold, Dieter Flesch-Janys, Judith Heinz, Nadia Obi, Ursula Eilber,
Muhabbet Celik; MBCSG: Paolo Peterlongo of IFOM, the FIRC Institute of
Molecular Oncology; Siranoush Manoukian, Bernard Peissel, Jacopo
Azzollini, Daniela Zaffaroni and Lidia Pezzani of the Fondazione IRCCS
Istituto Nazionale dei Tumori (INT); Bernardo Bonanni, and Irene Feroce
of the Istituto Europeo di Oncologia (IEO) and the personnel of the
Cogentech Cancer Genetic Test Laboratory; MTLGEBCS: We would like to
thank Martine Tranchant (CHU de Quebec Research Center), Marie-France
Valois, Annie Turgeon and Lea Heguy (McGill University Health Center,
Royal Victoria Hospital; McGill University) for DNA extraction, sample
management and skillful technical assistance. J.S. is Chairholder of the
Canada Research Chair in Oncogenetics. We thank study partcipants and
research staff (particularly Patsy Ng, Nurhidayu Hassan, Yoon Sook-Yee,
Daphne Lee, Lee Sheau Yee, Phuah Sze Yee and Norhashimah Hassan) for
their contributions and commitment to this study; NBCS: OSBREAC
Investigators: Prof. Solveig Hofvind, PhD (Cancer Registry of Norway,
Oslo, Norway, Oslo and Akershus University College of Applied Sciences,
Faculty of Health Science, Oslo, Norway), Prof. Tone F. Bathen, PhD
(Department of Circulation and Medical Imaging, Norwegian University of
Science and Technology NTNU), Trondheim, Norway), Dr. Elin Borgen, MD
(Department of Pathology, Division of Diagnostics and Intervention, Oslo
University Hospital, Oslo, Norway), Prof. Em. Oystein Fodstad, MD
(Department of Tumor Biology, Institute for Cancer Research, Oslo
University Hospital, Oslo, Norway and Institute for Clinical Medicine,
Faculty of Medicine, University of Oslo, Oslo, Norway), Dr.; Oystein
Garred, MD (Department of Pathology, Oslo University Hospital, Oslo,
Norway), Gry Aarum Geitvik, Unit leader (Department of Cancer Genetics,
Institute for Cancer Research, Oslo University
Hospital-Radiumhospitalet, Oslo, Norway), Prof. Gunhild Mari Maelandsmo,
PhD (Department of Tumor Biology, Institute for Cancer Research, Oslo
University Hospital, Oslo, Norway, Department of Pharmacy, Faculty of
Health Sciences, University of Tromso, Tromso, Norway), Dr. Hege G
Russnes, MD (Department of Cancer Genetics, Institute for Cancer
Research, Oslo University Hospital-Radiumhospitalet, Oslo, Norway and
Department of Pathology, Oslo University Hospital, Oslo, Norway), Dr.
Therese Sorlie, PhD (Department of Cancer Genetics, Institute for Cancer
Research, Oslo University Hospital-Radiumhospitalet, Oslo, Norway),
Prof. Ole Christian Lingjorde, PhD (Centre for Cancer Biomedicine,
University of Oslo, Oslo, Norway and Department of Computer Science,
University of Oslo, Oslo, Norway), Dr. Helle Kristine Skjerven, MD
(Breast and Endocrine Surgery, Department of Breast and Endocrine
Surgery, Vestre Viken Hospital, Drammen, Norway), Dr. Britt Fritzman, MD
(Ostfold Hospital, Ostfold, Norway); NBHS: We thank study participants
and research staff for their contributions and commitment to this study;
OBCS: We thank Arja Jukkola-Vuorinen, Mervi Grip, Saila Kauppila, Meeri
Otsukka, Leena Keskitalo and Kari Mononen for their contributions to
this study; OFBCR: Teresa Selander, Nayana Weerasooriya; PBCS: Louise
Brinton, Mark Sherman, Neonila Szeszenia-Dabrowska, Beata Peplonska,
Witold Zatonski, Pei Chao, Michael Stagner; RBCS: Petra Bos, Jannet
Blom, Ellen Crepin, Elisabeth Huijskens, Anja Kromwijk-Nieuwlaat,
Annette Heemskerk, the Erasmus MC Family Cancer Clinic; SASBAC: The
Swedish Medical Research Counsel; SBCGS: We thank study partcipants and
research staff for their contributions and commitment to this study;
SBCS: Sue Higham, Helen Cramp, Dan Connley, Ian Brock, Sabapathy
Balasubramanian and Malcolm W.R. Reed; SEARCH: The SEARCH and EPIC
teams; SGBCC: We thank the participants and research coordinator Ms Tan
Siew Li; SKKDKFZS: We thank all study participants, clinicians, family
doctors, researchers and technicians for their contributions and
commitment to this study; SZBCS: Ewa Putresza; UKBGS: We thank Breast
Cancer Now and the Institute of Cancer Research for support and funding
of the Breakthrough Generations Study, and the study participants, study
staff, and the doctors, nurses and other health care providers and
health information sources who have contributed to the study. We
acknowledge NHS funding to the Royal Marsden/ICR NIHR Biomedical
Research Centre.; This study was funded by the Cancer Genomics
Netherlands (CGC.nl) and a grant for the Netherlands Organization of
Scientific Research (NWO). J Liu received a scholarship from the China
Scholarship Council (Beijing, China). BCAC is funded by Cancer Research
UK [C1287/A10118, C1287/A12014] and by the European Community's Seventh
Framework Programme under grant agreement number 223175 (grant number
HEALTH-F2-2009-223175) (COGS). Funding for the iCOGS infrastructure came
from: the European Community's Seventh Framework Programme under grant
agreement no 223175 (HEALTH-F2-2009-223175) (COGS), Cancer Research UK
(C1287/A10118, C1287/A 10710, C12292/A11174, C1281/A12014, C5047/A8384,
C5047/A15007, C5047/A10692, C8197/A16565), the National Institutes of
Health (CA128978) and Post-Cancer GWAS initiative (1U19 CA148537, 1U19
CA148065 and 1U19 CA148112 - the GAME-ON initiative), the Department of
Defence (W81XWH-10-1-0341), the Canadian Institutes of Health Research
(CIHR) for the CIHR Team in Familial Risks of Breast Cancer, Komen
Foundation for the Cure, the Breast Cancer Research Foundation, and the
Ovarian Cancer Research Fund. The Australian Breast Cancer Family Study
(ABCFS) was supported by grant UM1 CA164920 from the National Cancer
Institute (USA). The content of this manuscript does not necessarily
reflect the views or policies of the National Cancer Institute or any of
the collaborating centers in the Breast Cancer Family Registry (BCFR),
nor does mention of trade names, commercial products, or organizations
imply endorsement by the USA Government or the BCFR. The ABCFS was also
supported by the National Health and Medical Research Council of
Australia, the New South Wales Cancer Council, the Victorian Health
Promotion Foundation (Australia) and the Victorian Breast Cancer
Research Consortium. J.L.H. is a National Health and Medical Research
Council (NHMRC) Senior Principal Research Fellow. M.C.S. is a NHMRC
Senior Research Fellow. The ABCS study was supported by the Dutch Cancer
Society [grants NKI 2007-3839; 2009 4363]. The ACP study is funded by
the Breast Cancer Research Trust, UK. The work of the BBCC was partly
funded by ELAN-Fond of the University Hospital of Erlangen. The BBCS is
funded by Cancer Research UK and Breast Cancer Now and acknowledges NHS
funding to the NIHR Biomedical Research Centre, and the National Cancer
Research Network (NCRN). ES is supported by NIHR Comprehensive
Biomedical Research Centre, Guy's & St. Thomas' NHS Foundation Trust in
partnership with King's College London, United Kingdom. IT is supported
by the Oxford Biomedical Research Centre. The BSUCH study was supported
by the Dietmar-Hopp Foundation, the Helmholtz Society and the German
Cancer Research Center (DKFZ). The CECILE study was supported by
Fondation de France, Institut National du Cancer (INCa), Ligue Nationale
contre le Cancer, Agence Nationale de Securite Sanitaire, de
l'Alimentation, de l'Environnement et du Travail (ANSES), Agence
Nationale de la Recherche (ANR). The CGPS was supported by the Chief
Physician Johan Boserup and Lise Boserup Fund, the Danish Medical
Research Council, and Herlev and Gentofte Hospital. The CNIO-BCS was
supported by the Instituto de Salud Carlos III (CEGEN) and grants from
the Fondo de Investigacion Sanitario (PI11/00923 and PI12/00070) with
FEDER funds and H2020 (BRIDGES project).; The CTS was initially
supported by the California Breast Cancer Act of 1993 and the California
Breast Cancer Research Fund (contract 97-10500) and is currently funded
through the National Institutes of Health (R01 CA77398, UM1 CA164917,
and U01 CA199277). Collection of cancer incidence data was supported by
the California Department of Public Health as part of the statewide
cancer reporting program mandated by California Health and Safety Code
Section 103885. HAC receives support from the Lon V Smith Foundation
(LVS39420). The 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 GENICA was
funded by the Federal Ministry of Education and Research (BMBF) Germany
grants 01KW9975/5, 01KW9976/8, 01KW9977/0 and 01KW0114, the Robert Bosch
Foundation, Stuttgart, Deutsches Krebsforschungszentrum (DKFZ),
Heidelberg, the Institute for Prevention and Occupational Medicine of
the German Social Accident Insurance, Institute of the Ruhr University
Bochum (IPA), Bochum, as well as the Department of Internal Medicine,
Evangelische Kliniken Bonn gGmbH, Johanniter Krankenhaus, Bonn, Germany.
The HEBCS was financilly supported by the Helsinki University Central
Hospital Research Fund, Academy of Finland (266528), the Finnish Cancer
Society, The Nordic Cancer Union and the Sigrid Juselius Foundation. The
HERPACC was supported by MEXT Kakenhi (No. 170150181 and 26253041) from
the Ministry of Education, Science, Sports, Culture and Technology of
Japan, by a Grant-in-Aid for the Third Term Comprehensive 10-Year
Strategy for Cancer Control from Ministry Health, Labour and Welfare of
Japan, by Health and Labour Sciences Research Grants for Research on
Applying Health Technology from Ministry Health, Labour and Welfare of
Japan, by National Cancer Center Research and Development Fund, and
"Practical Research for Innovative Cancer Control (15ck0106177h0001)"
from Japan Agency for Medical Research and development, AMED, and Cancer
Bio Bank Aichi. The HMBCS was supported by a grant from the Friends of
Hannover Medical School and by the Rudolf Bartling Foundation. The
pKARMA study was supported by Merit and Hans Rausings Initiative Against
Breast Cancer. The KBCP was financially supported by the special
Government Funding (EVO) of Kuopio University Hospital grants, Cancer
Fund of North Savo, the Finnish Cancer Organizations, and by the
strategic funding of the University of Eastern Finland. kConFab is
supported by a grant from the National Breast Cancer Foundation, and
previously by the National Health and Medical Research Council (NHMRC),
the Queensland Cancer Fund, the Cancer Councils of New South Wales,
Victoria, Tasmania and South Australia, and the Cancer Foundation of
Western Australia. Financial support for the AOCS was provided by the
United States Army Medical Research and Materiel Command
[DAMD17-01-1-0729], Cancer Council Victoria, Queensland Cancer Fund,
Cancer Council New South Wales, Cancer Council South Australia, The
Cancer Foundation of Western Australia, Cancer Council Tasmania and the
National Health and Medical Research Council of Australia (NHMRC;
400413, 400281, 199600). G.C.T. and P.W. are supported by the NHMRC. RB
was a Cancer Institute NSW Clinical Research Fellow. LAABC is supported
by grants (1RB-0287, 3PB-0102, 5PB-0018, 10PB-0098) from the California
Breast Cancer Research Program.; Incident breast cancer cases were
collected by the USC Cancer Surveillance Program (CSP) which is
supported under subcontract by the California Department of Health. The
CSP is also part of the National Cancer Institute's Division of Cancer
Prevention and Control Surveillance, Epidemiology, and End Results
Program, under contract number N01CN25403. LMBC is supported by the
'Stichting tegen Kanker'. Diether Lambrechts is supported by the FWO.
The MARIE study was supported by the Deutsche Krebshilfe e.V.
[70-2892-BR I, 106332, 108253, 108419, 110826, 110828], the Hamburg
Cancer Society, the German Cancer Research Center (DKFZ) and the Federal
Ministry of Education and Research (BMBF) Germany [01KH0402]. MBCSG is
supported by grants from the Italian Association for Cancer Research
(AIRC) and by funds from the Italian citizens who allocated the 5/1000
share of their tax payment in support of the Fondazione IRCCS Istituto
Nazionale Tumori, according to Italian laws (INT-Institutional strategic
projects "5 x 1000"). The MCBCS was supported by the NIH grants
CA192393, CA116167, CA176785 an NIH Specialized Program of Research
Excellence (SPORE) in Breast Cancer [CA116201], and the Breast Cancer
Research Foundation and a generous gift from the David F. and Margaret
T. Grohne Family Foundation. MCCS cohort recruitment was funded by
VicHealth and Cancer Council Victoria. The MCCS was further supported by
Australian NHMRC grants 209057, 251553 and 504711 and by infrastructure
provided by Cancer Council Victoria. Cases and their vital status were
ascertained through the Victorian Cancer Registry (VCR) and the
Australian Institute of Health and Welfare (AIHW), including the
National Death Index and the Australian Cancer Database. The MEC was
support by NIH grants CA63464, CA54281, CA098758, CA132839 and CA164973.
The work of MTLGEBCS was supported by the Quebec Breast Cancer
Foundation, the Canadian Institutes of Health Research for the " CIHR
Team in Familial Risks of Breast Cancer" program grant #CRN-87521 and
the Ministry of Economic Development, Innovation and Export Trade -
grant # PSR-SIIRI-701. MYBRCA is funded by research grants from the
Malaysian Ministry of Higher Education (UM.C/HlR/MOHE/06) and Cancer
Research Malaysia. MYMAMMO is supported by research grants from Yayasan
Sime Darby LPGA Tournament and Malaysian Ministry of Higher Education
(RP046B-15HTM). The NBCS has been supported by the Research Council of
Norway grant 193387/V50 (to A-L Borresen-Dale and V.N. Kristensen) and
grant 193387/H10 (to A-L Borresen-Dale and V.N. Kristensen), South
Eastern Norway Health Authority (grant 39346 to A-L Borresen-Dale and
27208 to V. N. Kristensen) and the Norwegian Cancer Society (to A-L
Borresen-Dale and 419616-71248 -PR-2006-0282 to V. N. Kristensen). It
has received funding from the K. G. Jebsen Centre for Breast Cancer
Research (2012-2015). The NBHS was supported by NIH grant R01CA100374.
Biological sample preparation was conducted the Survey and Biospecimen
Shared Resource, which is supported by P30 CA68485. The OBCS was
supported by research grants from the Finnish Cancer Foundation, the
Academy of Finland (grant number 250083, 122715 and Center of Excellence
grant number 251314), the Finnish Cancer Foundation, the Sigrid Juselius
Foundation, the University of Oulu, the University of Oulu Support
Foundation and the special Governmental EVO funds for Oulu University
Hospital-based research activities. The Ontario Familial Breast Cancer
Registry (OFBCR) was supported by grant UM1 CA164920 from the National
Cancer Institute (USA).; The content of this manuscript does not
necessarily reflect the views or policies of the National Cancer
Institute or any of the collaborating centers in the Breast Cancer
Family Registry (BCFR), nor does mention of trade names, commercial
products, or organizations imply endorsement by the USA Government or
the BCFR. The PBCS was funded by Intramural Research Funds of the
National Cancer Institute, Department of Health and Human Services, USA.
The RBCS was funded by the Dutch Cancer Society (DDHK 2004-3124, DDHK
2009-4318). The SASBAC study was supported by funding from the Agency
for Science, Technology and Research of Singapore (A*STAR), the US
National Institute of Health (NIH) and the Susan G. Komen Breast Cancer
Foundation. The SBCGS was supported primarily by NIH grants R01CA64277,
R01CA148667, UMCA182910, and R37CA70867. Biological sample preparation
was conducted the Survey and Biospecimen Shared Resource, which is
supported by P30 CA68485. The scientific development and funding of this
project were, in part, supported by the Genetic Associations and
Mechanisms in Oncology (GAME-ON) Network U19 CA148065. The SBCS was
supported by Sheffield Experimental Cancer Medicine Centre and Breast
Cancer Now. SEARCH is funded by a programme grant from Cancer Research
UK [C490/A10124] and supported by the UK National Institute for Health
Research Biomedical Research Centre at the University of Cambridge.
SEBCS was supported by the BRL (Basic Research Laboratory) program
through the National Research Foundation of Korea funded by the Ministry
of Education, Science and Technology (2012-0000347). SGBCC is funded by
the NUS start-up Grant, National University Cancer Institute Singapore
(NCIS) Centre Grant and the NMRC Clinician Scientist Award. Additional
controls were recruited by the Singapore Consortium of Cohort Studies-
Multi-ethnic cohort (SCCS-MEC), which was funded by the Biomedical
Research Council, grant number: 05/1/21/19/425. SKKDKFZS is supported by
the DKFZ. The SZBCS was supported by Grant PBZ_KBN_122/P05/2004. The
TBCS was funded by The National Cancer Institute Thailand. The TNBCC was
supported by: a Specialized Program of Research Excellence (SPORE) in
Breast Cancer (CA116201), a grant from the Breast Cancer Research
Foundation, a generous gift from the David F. and Margaret T. Grohne
Family Foundation; the Hellenic Cooperative Oncology Group research
grant (HR R_BG/04) and the Greek General Secretary for Research and
Technology (GSRT) Program, Research Excellence II, the European Union
(European Social Fund - ESF), and Greek national funds through the
Operational Program "Education and Lifelong Learning" of the National
Strategic Reference Framework (NSRF) - ARISTEIA. The TWBCS is supported
by the Taiwan Biobank project of the Institute of Biomedical Sciences,
Academia Sinica, Taiwan. The UKBGS is funded by Breast Cancer Now and
the Institute of Cancer Research (ICR), London. ICR acknowledges NHS
funding to the NIHR Biomedical Research Centre.
NR 29
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U1 9
U2 9
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 NOV 15
PY 2016
VL 6
AR 36874
DI 10.1038/srep36874
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EB8QC
UT WOS:000387654800001
PM 27845421
ER
PT J
AU Nakagawa-Goto, K
Taniguchi, Y
Watanabe, Y
Oda, A
Ohkoshi, E
Hamel, E
Lee, KH
Goto, M
AF Nakagawa-Goto, Kyoko
Taniguchi, Yukako
Watanabe, Yurie
Oda, Akifumi
Ohkoshi, Emika
Hamel, Ernest
Lee, Kuo-Hsiung
Goto, Masuo
TI Triethylated chromones with substituted naphthalenes as tubulin
inhibitors
SO BIOORGANIC & MEDICINAL CHEMISTRY
LA English
DT Article
DE Triethylated chromones; Naphthalene; Mitotic inhibitors
ID DESMOSDUMOTIN-B ANALOGS; COLCHICINE; AGENTS
AB Previously synthesized 2-(benzo[b]thiophene-3'-yI)-6,8,8-triethyldesmosdumotin B (1, TEDB-TB) and 2-(naphth-1'-yl)-6,8,8-triethyldesmosdumotin B (2) showed potent activity against multiple human tumor cell lines, including a multidrug-resistant (MDR) subline, by targeting spindle formation and/or the microtubule network. Consequently, ester analogues of hydroxylated naphthyl substituted TEBDs (3-5) were prepared and evaluated for their effects on tumor cell proliferation and on tubulin assembly. Among all new compounds, compound 6, a 4'-acetoxynaphthalen-1'-yl derivative, displayed the most potent antiproliferative activity (IC50, 0.2-5.7 mu M). Selected analogues were confirmed to be tubulin assembly inhibitors in cell-free and cell-based assays using MDR tumor cells. The new analogues partially inhibited colchicine binding to tubulin, suggesting their binding mode would be different from that of colchicine. This observation was supported by computational docking model analyses. Thus, the newly synthesized triethylated chromones with esterified naphthalene groups have good potential for development as a new class of mitotic inhibitors that target tubulin. (C) 2016 Elsevier Ltd. All rights reserved.
C1 [Nakagawa-Goto, Kyoko; Taniguchi, Yukako; Watanabe, Yurie; Oda, Akifumi] Kanazawa Univ, Sch Pharmaceut Sci, Coll Med Pharmaceut & Hlth Sci, Kanazawa, Ishikawa 9201192, Japan.
[Nakagawa-Goto, Kyoko; Ohkoshi, Emika; Lee, Kuo-Hsiung; Goto, Masuo] Univ N Carolina, UNC Eshelman Sch Pharm, Nat Prod Res Labs, Chapel Hill, NC 27599 USA.
[Hamel, Ernest] NCI, Screening Technol Branch, Dev Therapeut Program, Div Canc Treatment & Diag,Frederick Natl Lab Canc, Frederick, MD 21702 USA.
[Lee, Kuo-Hsiung] China Med Univ & Hosp, Chinese Med Res & Dev Ctr, 2 Yuh Der Rd, Taichung 40447, Taiwan.
RP Nakagawa-Goto, K (reprint author), Kanazawa Univ, Sch Pharmaceut Sci, Coll Med Pharmaceut & Hlth Sci, Kanazawa, Ishikawa 9201192, Japan.; Nakagawa-Goto, K; Goto, M (reprint author), Univ N Carolina, UNC Eshelman Sch Pharm, Nat Prod Res Labs, Chapel Hill, NC 27599 USA.
EM kngoto@p.kanazawa-u.ac.jp; goto@med.unc.edu
RI GOTO, Kyoko/D-8389-2015
OI GOTO, Kyoko/0000-0002-1642-6538
FU Ministry of Education, Culture, Sports, Science, and Technology (MEXT
KAKENHI, Japan) [25293024, 25670054, 26460034, 15H01064]; Terumo Life
Science Foundation; NIH grant from the National Cancer Institute
[CA177584]; University Research Council (UNC); IBM Junior Faculty
Development Award; Eshelman Institute for Innovation, Chapel Hill, North
Carolina
FX We wish to thank the Microscopy Service Laboratory (UNC-CH) for their
expertise in fluorescence and confocal microscopy. In addition, we
appreciate critical comments, suggestions, and editing of the manuscript
by Dr. Susan L. Morris-Natschke (UNC-CH). This study was supported by
Grant-in-Aid from the Ministry of Education, Culture, Sports, Science,
and Technology (MEXT KAKENHI, Japan), awarded to K.N.G. (Grant Numbers
25293024 & 25670054) and A.O. (Grant Numbers 26460034 & 15H01064), as
well as by a grant from the Terumo Life Science Foundation awarded to
K.N.G. This work was supported in part by NIH grant CA177584 from the
National Cancer Institute awarded to K.H.L. This work was also supported
by a grant from the University Research Council (UNC), and the IBM
Junior Faculty Development Award, as well as the Eshelman Institute for
Innovation, Chapel Hill, North Carolina, awarded to M.G. The content of
this paper is solely the responsibility of the authors and does not
necessarily reflect the official views of the National Institutes of
Health.
NR 14
TC 0
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U1 5
U2 5
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0968-0896
EI 1464-3391
J9 BIOORGAN MED CHEM
JI Bioorg. Med. Chem.
PD NOV 15
PY 2016
VL 24
IS 22
BP 6048
EP 6057
DI 10.1016/j.bmc.2016.09.062
PG 10
WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry,
Organic
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry
GA EB2NV
UT WOS:000387200000037
PM 27707623
ER
PT J
AU Farrand, AQ
Gregory, RA
Backman, CM
Helke, KL
Boger, HA
AF Farrand, Ariana Q.
Gregory, Rebecca A.
Backman, Cristina M.
Helke, Kristi L.
Boger, Heather A.
TI Altered glutamate release in the dorsal striatum of the MitoPark mouse
model of Parkinson's disease
SO BRAIN RESEARCH
LA English
DT Article
DE In vivo electrochemistry; Glutamate; Striatum; Neurodegeneration;
MitoPark; Dopamine
ID SUBSTANTIA-NIGRA; INDUCED DYSKINESIAS; PREFRONTAL CORTEX; BASAL GANGLIA;
ANIMAL-MODELS; RAT STRIATUM; MICE; MICROELECTRODE; RECEPTORS; GDNF
AB Mitochondrial dysfunction has been implicated in the degeneration of dopamine (DA) neurons in Parkinson's disease (PD). In addition, animal models of PD utilizing neurotoxins, such as 6-hydroxydopamine and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, have shown that these toxins disrupt mitochondrial respiration by targeting complex I of the electron transport chain, thereby impairing DA neurons in these models. A MitoPark mouse model was created to mimic the mitochondrial dysfunction observed in the DA system of PD patients. These mice display the same phenotypic characteristics as PD, including accelerated decline in motor function and DAergic systems with age. Previously, these mice have responded to L-Dopa treatment and develop L-Dopa induced dyskinesia (LID) as they age. A potential mechanism involved in the formation of LID is greater glutamate release into the dorsal striatum as a result of altered basal ganglia neurocircuitry due to reduced nigrostriatal DA neurotransmission. Therefore, the focus of this study was to assess various indicators of glutamate neurotransmission in the dorsal striatum of MitoPark mice at an age in which nigrostriatal DA has degenerated. At 28 weeks of age, MitoPark mice had, upon KCl stimulation, greater glutamate release in the dorsal striatum compared to control mice. In addition, uptake kinetics were slower in MitoPark mice. These findings were coupled with reduced expression of the glutamate re-uptake transporter, GLT-1, thus providing an environment suitable for glutamate excitotoxic events, leading to altered physiological function in these mice. (C) 2016 Elsevier B.V. All rights reserved.
C1 [Farrand, Ariana Q.; Gregory, Rebecca A.; Boger, Heather A.] Med Univ South Carolina, Dept Neurosci, 173 Ashley Ave,BSB 403,MSC 510, Charleston, SC 29425 USA.
[Farrand, Ariana Q.; Gregory, Rebecca A.; Boger, Heather A.] Med Univ South Carolina, Ctr Aging, 173 Ashley Ave,BSB 403,MSC 510, Charleston, SC 29425 USA.
[Gregory, Rebecca A.; Helke, Kristi L.] Med Univ South Carolina, Dept Comparat Med, 114 Doughty St,STB 648,MSC 777, Charleston, SC 29425 USA.
[Backman, Cristina M.] NIH, Integrat Neurosci Sect, Natl Inst Drug Abuse Intramural Res Program, 251 Bayview Blvd, Baltimore, MD 21224 USA.
RP Boger, HA (reprint author), Med Univ South Carolina, Dept Neurosci, 173 Ashley Ave,BSB 403,MSC 510, Charleston, SC 29425 USA.; Boger, HA (reprint author), Med Univ South Carolina, Ctr Aging, 173 Ashley Ave,BSB 403,MSC 510, Charleston, SC 29425 USA.
EM boger@musc.edu
OI Helke, Kris/0000-0001-9746-0764
FU MUSC Barmore Fund, Charleston, SC; National Institute on Aging at the
National Institutes of Health [4R00AG033687]
FX This work was supported by the MUSC Barmore Fund, Charleston, SC and the
National Institute on Aging at the National Institutes of Health (Grant
4R00AG033687).
NR 41
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Z9 0
U1 5
U2 5
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0006-8993
EI 1872-6240
J9 BRAIN RES
JI Brain Res.
PD NOV 15
PY 2016
VL 1651
BP 88
EP 94
DI 10.1016/j.brainres.2016.09.025
PG 7
WC Neurosciences
SC Neurosciences & Neurology
GA EB6WU
UT WOS:000387527100010
PM 27659966
ER
PT J
AU Bakir, M
Nelson, MD
Jones, E
Li, QL
Wei, J
Sharif, B
Minissian, M
Shufelt, C
Sopko, G
Pepine, CJ
Merz, CNB
AF Bakir, May
Nelson, Michael D.
Jones, Erika
Li, Quanlin
Wei, Janet
Sharif, Behzad
Minissian, Margo
Shufelt, Chrisandra
Sopko, George
Pepine, Carl J.
Merz, C. Noel Bairey
TI Heart failure hospitalization in women with signs and symptoms of
ischemia: A report from the women's ischemia syndrome evaluation study
SO INTERNATIONAL JOURNAL OF CARDIOLOGY
LA English
DT Article
DE Heart failure; Heart failure with preserved ejection fraction; Coronary
microvascular disease; Women; Coronary artery disease
ID SYNDROME EVALUATION WISE; CORONARY-ARTERY-DISEASE; PRESERVED EJECTION
FRACTION; NATIONAL-HEART; RISK-FACTORS; EPIDEMIOLOGY; REACTIVITY;
HEALTH; LUNG
AB Background: Women with signs and symptoms of ischemia, no obstructive coronary artery disease, and preserved left ventricular ejection fraction enrolled in the National Heart Lung and Blood Institute (NHLBI) sponsored Women's Ischemia Syndrome Evaluation (WISE) study have an unexpectedly high rate of subsequent heart failure (HF) hospitalization. We sought to verify and characterize the HF hospitalizations.
Methods: A retrospective chart review was performed on 223 women with signs and symptoms of ischemia, undergoing coronary angiography for suspected coronary artery disease followed for 6 +/- 2.6 years. Data were collected from a single site in the WISE study.
Results: At the time of study enrollment, the women were 57 +/- 11 years of age, all had preserved left ventricular ejection fraction, and 81 (36%) had obstructive CAD (defined as >50% stenosis in at least one epicardial artery). Among the 223 patients, 25 (11%) reported HF hospitalizations, of which 14/25 (56%) had recurrent HF hospitalizations (>2 hospitalizations). Medical records were available in 13/25 (52%) women. Left ventricular ejection fraction was measured in all verified cases and was found to be preserved in 12/13 (92%). HF hospitalization was not related to obstructive CAD.
Conclusion: Among women with signs and symptoms of ischemia undergoing coronary angiography for suspected obstructive CAD, HF hospitalization at 6-year follow-up was predominantly characterized by a preserved ejection fraction and not associated with obstructive CAD. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
C1 [Bakir, May; Nelson, Michael D.; Jones, Erika; Wei, Janet; Minissian, Margo; Shufelt, Chrisandra; Merz, C. Noel Bairey] Cedars Sinai Heart Inst, Barbra Streisand Womens Heart Ctr, Los Angeles, CA USA.
[Li, Quanlin] Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Inst, Biostat & Bioinformat, Los Angeles, CA 90048 USA.
[Sharif, Behzad] Cedars Sinai Med Ctr, Biomed Imaging Res Inst, Los Angeles, CA 90048 USA.
[Sopko, George] NHLBI, Bldg 10, Bethesda, MD 20892 USA.
[Pepine, Carl J.] Univ Florida, Gainesville, FL USA.
RP Merz, CNB (reprint author), Cedars Sinai Med Ctr, Womens Heart Ctr, 127 S San Vicente Blvd,A3906, Los Angeles, CA 90048 USA.
EM merz@cshs.org
OI Bakir, May/0000-0002-8924-425X
FU National Heart, Lung and Blood Institutes [N01-HV-68161, N01-HV-68162,
N01-HV-68163, N01-HV-68164, U0164829, U01 HL649141, U01 HL649241,
K23HL105787, T32HL69751, T32HL116273, R01 HL090957, 1R03AG032631];
National Institute on Aging; GCRC [MO1-RR00425]; National Center for
Research Resources; National Center for Advancing Translational Sciences
Grant [UL1TR000124, UL1TR000064]; Gustavus and Louis Pfeiffer Research
Foundation, Danville, NJ; Women's Guild of Cedars-Sinai Medical Center,
Los Angeles, CA; Ladies Hospital Aid Society of Western Pennsylvania,
Pittsburgh, PA; QMED, Inc., Laurence Harbor, NJ; Edythe L. Broad Women's
Heart Research Fellowship, Cedars-Sinai Medical Center, Los Angeles,
California; Constance Austin Women's Heart Research Fellowship,
Cedars-Sinai Medical Center, Los Angeles, California; Barbra Streisand
Women's Cardiovascular Research and Education Program, Cedars-Sinai
Medical Center, Los Angeles; Society for Women's Health Research (SWHR),
Washington, D.C.; Linda Joy Pollin Women's Heart Health Program,
Cedars-Sinai Medical Center, Los Angeles, California; American Heart
Association [16SDG27260115]; Harry S. Moss Heart Trust; Erika Glazer
Women's Heart Health Project, Cedars-Sinai Medical Center, Los Angeles,
California
FX This work was supported by contracts from the National Heart, Lung and
Blood Institutes nos. N01-HV-68161, N01-HV-68162, N01-HV-68163,
N01-HV-68164, U0164829, U01 HL649141, U01 HL649241, K23HL105787,
T32HL69751, T32HL116273, R01 HL090957, and 1R03AG032631; from the
National Institute on Aging; from GCRC grant MO1-RR00425; from the
National Center for Research Resources; from the National Center for
Advancing Translational Sciences Grant UL1TR000124 and UL1TR000064; and
from the Gustavus and Louis Pfeiffer Research Foundation, Danville, NJ,
The Women's Guild of Cedars-Sinai Medical Center, Los Angeles, CA, The
Ladies Hospital Aid Society of Western Pennsylvania, Pittsburgh, PA, and
QMED, Inc., Laurence Harbor, NJ, the Edythe L. Broad and the Constance
Austin Women's Heart Research Fellowships, Cedars-Sinai Medical Center,
Los Angeles, California, the Barbra Streisand Women's Cardiovascular
Research and Education Program, Cedars-Sinai Medical Center, Los
Angeles, The Society for Women's Health Research (SWHR), Washington,
D.C., The Linda Joy Pollin Women's Heart Health Program, the Erika
Glazer Women's Heart Health Project, Cedars-Sinai Medical Center, Los
Angeles, California, the American Heart Association (16SDG27260115) and
the Harry S. Moss Heart Trust.
NR 18
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Z9 0
U1 2
U2 2
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0167-5273
EI 1874-1754
J9 INT J CARDIOL
JI Int. J. Cardiol.
PD NOV 15
PY 2016
VL 223
BP 936
EP 939
DI 10.1016/j.ijcard.2016.07.301
PG 4
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA EB0LV
UT WOS:000387036200240
PM 27589041
ER
PT J
AU Knudsen, GA
Hughes, MF
Sanders, JM
Hall, SM
Birnbaum, LS
AF Knudsen, Gabriel A.
Hughes, Michael F.
Sanders, J. Michael
Hall, Samantha M.
Birnbaum, Linda S.
TI Estimation of human percutaneous bioavailability for two novel
brominated flame retardants, 2-ethylhexyl 2,3,4,5-tetrabromobenzoate
(EH-TBB) and bis(2-ethylhexyl) tetrabromophthalate (BEH-TEBP)
SO TOXICOLOGY AND APPLIED PHARMACOLOGY
LA English
DT Article
DE Dermal bioavailability; Brominated flame retardant; 2-Ethylhexyl
2-3,4,5-tetrabromobenzoate; Bis(2-ethylhexyl) tetrabromophthalate;
Parallelogram method; Persistent organic pollutant
ID IN-HOUSE DUST; ENDOCRINE DISRUPTING CHEMICALS; POLYBROMINATED DIPHENYL
ETHERS; MIXTURE FIREMASTER(R) 550; VITRO DERMAL ABSORPTION; GREAT-LAKES
ATMOSPHERE; RAT SKIN ABSORPTION; EARLY-LIFE EXPOSURE; INDOOR DUST;
PARALLELOGRAM METHOD
AB 2-Ethylhexyl-2,3,4,5-tetrabromobenzoate (EH-TBB) and bis(2-ethylhexyl)tetrabromophthalate (BEH-TEBP) are novel brominated flame retardants used in consumer products. A parallelogram approach was used to predict human dermal absorption and flux for EH-TBB and BEH-TEBP. [C-14]-EH-TBB or [C-14]-BEH-TEBP was applied to human or rat skin at 100 nmol/cm(2) using a flow-through system. Intact rats received analogous dermal doses. Treated skin was washed and tape-stripped to remove "unabsorbed" [C-14]-radioactivity after continuous exposure (24 h). "Absorbed" was quantified using dermally retained [C-14]-radioactivity; "penetrated" was calculated based on [C-14]-radioactivity in media (in vitro) or excreta + tissues (in vivo). Human skin absorbed EH-TBB (24 +/- 1%) while 0.2 +/- 0.1% penetrated skin. Rat skin absorbed more (51 +/- 10%) and was more permeable (2 +/- 0.5%) to EH-TBB in vitro; maximal EH-TBB flux was 11 +/- 7 and 102 +/- 24 pmol-eq/cm(2)/h for human and rat skin, respectively. In vivo, 27 +/- 5% was absorbed and 13% reached systemic circulation after 24 h (maximum flux was 464 +/- 65 pmol-eq/cm(2)/h). BEH-TEBP in vitro penetrance was minimal (<0.01%) for rat or human skin. BEH-TEBP absorption was 12 +/- 11% for human skin and 41 +/- 3% for rat skin. In vivo, total absorption was 27 +/- 9%; 12% reached systemic circulation. In vitro maximal BEH-TEBP flux was 0.3 +/- 0.2 and 1 +/- 0.3 pmol-eq/cm2/h for human and rat skin; in vivo maximum flux for rat skin was 16 +/- 7 pmol-eq/cm2/h. EH-TBB was metabolized in rat and human skin to tetrabromobenzoic acid. BEH-TEBP-derived [C-14] -radioactivity in the perfusion media could not be characterized. <1% of the dose of EH-TBB and BEH-TEHP is estimated to reach the systemic circulation following human dermal exposure under the conditions tested.
Chemical compounds studied in this article: 2-Ethylhexyl 2,3,4,5-tetrabromobenzoate (PubChem CID: 71316600; CAS No. 183658-27-7 FW: 549.92 g/mol logP(est): 7.73-8.75 (12)) Abdallah et al., 2015a. Other published abbreviations for 2-ethylhexyl-2,3,4,5-tetrabromobenzoate are TBB EHTeBB or EHTBB Abdallah and Harrad, 2011. bis(2-ethylhexyl) tetrabromophthalate (PubChem CID: 117291; CAS No. 26040-51-7 FW: 706.14 g/mol logP(est): 9.48-11.95 (12)). Other published abbreviations for bis(2-ethylhexyl)tetrabromophthalate are TeBrDEPH TBPH or BEHTBP. Published by Elsevier Inc.
C1 [Knudsen, Gabriel A.; Sanders, J. Michael; Hall, Samantha M.; Birnbaum, Linda S.] NCI, Lab Toxicol & Toxicokinet, 111 TW Alexander Dr, Res Triangle Pk, NC USA.
[Hughes, Michael F.] US EPA, Integrated Syst Toxicol Div, Natl Hlth & Environm Effects Res Lab, Off Res & Dev, Res Triangle Pk, NC 27711 USA.
RP Knudsen, GA (reprint author), 111 TW Alexander Dr,BG 101 Rm C220A, Res Triangle Pk, NC 27709 USA.
EM gabriel.knudsen@nih.gov
OI Hall, Samantha M./0000-0003-1608-9508
FU Intramural Research Program of NIH/NCI [ZIA BC 011476]
FX The authors would like to thank Ms. Brenda Edwards, Mr. Ethan Hull, Ms.
Katelyn McIntosh and Mr. Vivek Miyani, for technical assistance. This
article has been reviewed in accordance with the policy of the National
Health and Environmental Effects Research Laboratory, U.S. Environmental
Protection Agency, and approved for publication. Approval does not
signify that the contents necessarily reflect the views and policies of
the Agency, nor does mention of trade names or commercial products
constitute endorsement or recommendation for use. This research was
supported in part by the Intramural Research Program of NIH/NCI (Project
ZIA BC 011476).
NR 96
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U2 7
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 NOV 15
PY 2016
VL 311
BP 117
EP 127
DI 10.1016/j.taap.2016.10.005
PG 11
WC Pharmacology & Pharmacy; Toxicology
SC Pharmacology & Pharmacy; Toxicology
GA EA9VI
UT WOS:000386992400013
PM 27732871
ER
PT J
AU Kaczkurkin, AN
Moore, TM
Ruparel, K
Ciric, R
Calkins, ME
Shinohara, RT
Elliott, MA
Hopson, R
Roalf, DR
Vandekar, SN
Gennatas, ED
Wolf, DH
Scott, JC
Pine, DS
Leibenluft, E
Detre, JA
Foa, EB
Gur, RE
Gur, RC
Satterthwaite, TD
AF Kaczkurkin, Antonia N.
Moore, Tyler M.
Ruparel, Kosha
Ciric, Rastko
Calkins, Monica E.
Shinohara, Russell T.
Elliott, Mark A.
Hopson, Ryan
Roalf, David R.
Vandekar, Simon N.
Gennatas, Efstathios D.
Wolf, Daniel H.
Scott, J. Cobb
Pine, Daniel S.
Leibenluft, Ellen
Detre, John A.
Foa, Edna B.
Gur, Raquel E.
Gur, Ruben C.
Satterthwaite, Theodore D.
TI Elevated Amygdala Perfusion Mediates Developmental Sex Differences in
Trait Anxiety
SO BIOLOGICAL PSYCHIATRY
LA English
DT Article
DE Adolescence; Amygdala; Anxiety; Cerebral blood flow; Depression; Insula;
Perfusion
ID CEREBRAL-BLOOD-FLOW; PHILADELPHIA NEURODEVELOPMENTAL COHORT;
POSTTRAUMATIC-STRESS-DISORDER; MESSENGER-RNA EXPRESSION; COMMON
MENTAL-DISORDERS; FUNCTIONAL CONNECTIVITY; FEARFUL FACES; WHITE-MATTER;
HUMAN BRAIN; INDIVIDUAL-DIFFERENCES
AB BACKGROUND: Adolescence is a critical period for emotional maturation and is a time when clinically significant symptoms of anxiety and depression increase, particularly in females. However, few studies relate developmental differences in symptoms of anxiety and depression to brain development. Cerebral blood flow is one brain phenotype that is known to have marked developmental sex differences.
METHODS: We investigated whether developmental sex differences in cerebral blood flow mediated sex differences in anxiety and depression symptoms by capitalizing on a large sample of 875 youths who completed cross-sectional imaging as part of the Philadelphia Neurodevelopmental Cohort. Perfusion was quantified on a voxelwise basis using arterial spin-labeled magnetic resonance imaging at 3T. Perfusion images were related to trait and state anxiety using general additive models with penalized splines, while controlling for gray matter density on a voxelwise basis. Clusters found to be related to anxiety were evaluated for interactions with age, sex, and puberty.
RESULTS: Trait anxiety was associated with elevated perfusion in a network of regions including the amygdala, anterior insula, and fusiform cortex, even after accounting for prescan state anxiety. Notably, these relationships strengthened with age and the transition through puberty. Moreover, higher trait anxiety in postpubertal females was mediated by elevated perfusion of the left amygdala.
CONCLUSIONS: Taken together, these results demonstrate that differences in the evolution of cerebral perfusion during adolescence may be a critical element of the affective neurobiological characteristics underlying sex differences in anxiety and mood symptoms.
C1 [Kaczkurkin, Antonia N.; Moore, Tyler M.; Ruparel, Kosha; Ciric, Rastko; Calkins, Monica E.; Hopson, Ryan; Roalf, David R.; Gennatas, Efstathios D.; Wolf, Daniel H.; Scott, J. Cobb; Foa, Edna B.; Gur, Raquel E.; Gur, Ruben C.; Satterthwaite, Theodore D.] Univ Penn, Perelman Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA.
[Shinohara, Russell T.; Vandekar, Simon N.] Univ Penn, Perelman Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA.
[Elliott, Mark A.; Detre, John A.; Gur, Raquel E.; Gur, Ruben C.] Univ Penn, Perelman Sch Med, Dept Radiol, Philadelphia, PA 19104 USA.
[Detre, John A.] Univ Penn, Dept Neurol, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Scott, J. Cobb; Gur, Ruben C.] Philadelphia Vet Adm Med Ctr, Philadelphia, PA USA.
[Pine, Daniel S.; Leibenluft, Ellen] NIMH, Emot & Dev Branch, Intramural Res Program, Bethesda, MD 20892 USA.
RP Satterthwaite, TD (reprint author), Hosp Univ Penn, Dept Psychiat, 34th & Spruce St,10th Floor,Gates Bldg, Philadelphia, PA 19104 USA.
EM sattertt@upenn.edu
FU National Institute of Mental Health RC2 Grant [MH089983, MH089924,
R01MH07703]; National Institutes of Health [K23MH098130, R01MH101111,
K01MH102609, K08MH079364, R01NS085211, P50mh096891, T32MH065218];
Dowshen Program for Neuroscience; Center for Biomedical Computing and
Image Analysis (CBICA) at the University of Pennsylvania; Oxford
University Press
FX This work was supported by the National Institute of Mental Health RC2
Grant Nos. MH089983, MH089924, and R01MH07703. Additional support was
provided by the National Institutes of Health Grant Nos. K23MH098130 (to
TDS), R01MH101111 (to DHW), K01MH102609 (to DRR), K08MH079364 (to MEC),
R01NS085211 (to RTS), P50mh096891 (to REG), and T32MH065218 (to SNV);
and the Dowshen Program for Neuroscience. Support for developing
statistical analyses (to RTS and TDS) was provided by a seed grant by
the Center for Biomedical Computing and Image Analysis (CBICA) at the
University of Pennsylvania. The data reported in this article have been
deposited in the database of Genotypes and Phenotypes (dbGaP), available
at: www.ncbi.nlm.nih.gov/gap (accession no. phs000607.v1.p1).; REG
participated in an advisory board for Otsuka Pharmaceuticals. RCG
receives royalties from the Brain Resource Centre and serves without
compensation on an advisory board for Lumosity. EBF receives royalties
from the sale of the books Prolonged Exposure Therapy for PTSD:
Emotional Processing of Traumatic Experiences Therapist Guide and
Reclaiming Your Life From a Traumatic Experience Workbook by Oxford
University Press and receives payment for training workshops she
conducts on prolonged exposure therapy. All other authors reported no
biomedical financial interests or potential conflicts of interest.
NR 98
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U1 8
U2 8
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0006-3223
EI 1873-2402
J9 BIOL PSYCHIAT
JI Biol. Psychiatry
PD NOV 15
PY 2016
VL 80
IS 10
BP 775
EP 785
DI 10.1016/j.biopsych.2016.04.021
PG 11
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA DZ0FS
UT WOS:000385513500008
PM 27395327
ER
PT J
AU Chung, EJ
Sowers, A
Thetford, A
McKay-Corkum, G
Chung, SI
Mitchell, JB
Citrin, DE
AF Chung, Eun Joo
Sowers, Anastasia
Thetford, Angela
McKay-Corkum, Grace
Chung, Su I.
Mitchell, James B.
Citrin, Deborah E.
TI Mammalian Target of Rapamycin Inhibition With Rapamycin Mitigates
Radiation-Induced Pulmonary Fibrosis in a Murine Model
SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
LA English
DT Article
ID MTOR INHIBITORS; CELLULAR SENESCENCE; THORACIC IRRADIATION; SECRETORY
PHENOTYPE; CANCER-CELLS; LIFE-SPAN; LUNG; MICE; BINDING;
RADIOSENSITIVITY
AB Purpose: Radiation-induced pulmonary fibrosis (RIPF) is a late toxicity of therapeutic radiation. Signaling of the mammalian target of rapamycin drives several processes implicated in RIPF, including inflammatory cytokine production, fibroblast proliferation, and epithelial senescence. We sought to determine if mammalian target of rapamycin inhibition with rapamycin would mitigate RIPF.
Methods and Materials: C57BL/6NCr mice received a diet formulated with rapamycin (14 mg/kg food) or a control diet 2 days before and continuing for 16 weeks after exposure to 5 daily fractions of 6 Gy of thoracic irradiation. Fibrosis was assessed with Masson trichrome staining and hydroxyproline assay. Cytokine expression was evaluated by quantitative real-time polymerase chain reaction. Senescence was assessed by staining for beta-galactosidase activity.
Results: Administration of rapamycin extended the median survival of irradiated mice compared with the control diet from 116 days to 156 days (P = .006, log-rank test). Treatment with rapamycin reduced hydroxyproline content compared with the control diet (irradiation plus vehicle, 45.9 +/- 11.8 mu g per lung; irradiation plus rapamycin, 21.4 +/- 6.0 mu g per lung; P = .001) and reduced visible fibrotic foci. Rapamycin treatment attenuated interleukin 1 beta and transforming growth factor beta induction in irradiated lungs compared with the control diet. Type II pneumocyte senescence after irradiation was reduced with rapamycin treatment at 16 weeks (3-fold reduction at 16 weeks, P < .001).
Conclusions: Rapamycin protected against RIPF in a murine model. Rapamycin treatment reduced inflammatory cytokine expression, extracellular matrix production, and senescence in type II pneumocytes. Published by Elsevier Inc.
C1 [Chung, Eun Joo; McKay-Corkum, Grace; Chung, Su I.; Citrin, Deborah E.] NIH, Radiat Oncol Branch, Ctr Canc Res, Bldg 10, Bethesda, MD 20892 USA.
[Sowers, Anastasia; Thetford, Angela; Mitchell, James B.] NIH, Radiat Biol Branch, Ctr Canc Res, Bldg 10, Bethesda, MD 20892 USA.
RP Citrin, DE (reprint author), NCI, Radiat Oncol Branch, Bldg 10 CRC,B2-3500, Bethesda, MD 20892 USA.
EM citrind@mail.nih.gov
FU Intramural Research Program of the National Institutes of
Health-National Cancer Institute
FX This research was supported in part by the Intramural Research Program
of the National Institutes of Health-National Cancer Institute.
NR 54
TC 0
Z9 0
U1 8
U2 8
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0360-3016
EI 1879-355X
J9 INT J RADIAT ONCOL
JI Int. J. Radiat. Oncol. Biol. Phys.
PD NOV 15
PY 2016
VL 96
IS 4
BP 857
EP 866
DI 10.1016/j.ijrobp.2016.07.026
PG 10
WC Oncology; Radiology, Nuclear Medicine & Medical Imaging
SC Oncology; Radiology, Nuclear Medicine & Medical Imaging
GA DZ0JG
UT WOS:000385524000019
PM 27663762
ER
PT J
AU Shen, CC
Li, XZ
Rasooly, A
Guo, LY
Zhang, KN
Yang, MH
AF Shen, Congcong
Li, Xiangzhi
Rasooly, Avraham
Guo, Linyan
Zhang, Kaina
Yang, Minghui
TI A single electrochemical biosensor for detecting the activity and
inhibition of both protein kinase and alkaline phosphatase based on
phosphate ions induced deposition of redox precipitates
SO BIOSENSORS & BIOELECTRONICS
LA English
DT Article
DE Protein kinase; Alkaline phosphatase; Electrochemical; Biosensor;
Inhibitor
ID ELECTROGENERATED CHEMILUMINESCENCE BIOSENSOR; CARBON QUANTUM DOTS;
SIGNAL AMPLIFICATION; FLUORESCENT ASSAY; CANCER-THERAPY; A ACTIVITY;
PHOS-TAG; GRAPHENE; PHOSPHORYLATION; NANOPARTICLES
AB Protein kinase (PIGS) and alkaline phosphatase (ALP) are clinically relevant enzymes for a number of diseases. In this work, we developed a new simple electrochemical biosensor for the detection of the activity and inhibition of both PICA and ALP. One common feature of the PICA and ALP catalyzing process is that PICA can hydrolysis adenosine-5'-triphosphate (ATP) and ALP can hydrolysis pyrophosphate, both reactions produce phosphate ions, and the amount of phosphate ion produced is proportional to enzyme activity. Our assay is based on the principle that phosphate ions react with molybdate to form redox molybdophosphate precipitates on the electrode surface, thus generating electrochemical current. The detection limit for PICA and ALP were much lower than existing assays. The biosensor has good specificity and was used to measure drug-stimulated PICA from lysates of HeLa cells. We also evaluated the use of the biosensor as a screening tool for enzyme inhibitors. To the best of our knowledge, this is the first report of a biosensor capable of detecting the activity of both PICA and ALP. This tool has the potential to simplify PICA and ALP clinical measurement, thereby improving diagnostics of relevant diseases. It also may serve as the basis for a simple screening method for new enzyme inhibitors for disease treatment. (C) 2016 Elsevier B.V. All rights reserved.
C1 [Shen, Congcong; Li, Xiangzhi; Guo, Linyan; Zhang, Kaina; Yang, Minghui] Cent S Univ, Coll Chem & Chem Engn, Changsha 410083, Hunan, Peoples R China.
[Rasooly, Avraham] NCI, NIH, Rockville, MD 20850 USA.
RP Yang, MH (reprint author), Cent S Univ, Coll Chem & Chem Engn, Changsha 410083, Hunan, Peoples R China.
EM yangminghui@csu.edu.cn
FU National Key Basic Research Program of China [2014CB744502]; National
Natural Science Foundation of China [21575165]; Natural Science
Foundation of Hunan Province, China [2015JJ1019]
FX The authors thank the support of this work by the National Key Basic
Research Program of China (2014CB744502), the National Natural Science
Foundation of China (No. 21575165) and the Natural Science Foundation of
Hunan Province, China (No. 2015JJ1019).
NR 54
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U1 104
U2 128
PU ELSEVIER ADVANCED TECHNOLOGY
PI OXFORD
PA OXFORD FULFILLMENT CENTRE THE BOULEVARD, LANGFORD LANE, KIDLINGTON,
OXFORD OX5 1GB, OXON, ENGLAND
SN 0956-5663
EI 1873-4235
J9 BIOSENS BIOELECTRON
JI Biosens. Bioelectron.
PD NOV 15
PY 2016
VL 85
BP 220
EP 225
DI 10.1016/j.bios.2016.05.025
PG 6
WC Biophysics; Biotechnology & Applied Microbiology; Chemistry, Analytical;
Electrochemistry; Nanoscience & Nanotechnology
SC Biophysics; Biotechnology & Applied Microbiology; Chemistry;
Electrochemistry; Science & Technology - Other Topics
GA DU7QQ
UT WOS:000382410100029
ER
PT J
AU Pastor, M
Song, J
Hoang, DT
Jo, J
AF Pastor, Marissa
Song, Juyong
Danh-Tai Hoang
Jo, Junghyo
TI Minimal perceptrons for memorizing complex patterns
SO PHYSICA A-STATISTICAL MECHANICS AND ITS APPLICATIONS
LA English
DT Article
DE Perceptrons; Network complexity; Binary patterns; Memory storage;
Network architecture
ID FEEDFORWARD NEURAL-NETWORKS; STORAGE CAPACITY; HIDDEN UNITS; NUMBER;
CLASSIFICATION; ALGORITHMS
AB Feedforward neural networks have been investigated to understand learning and memory, as well as applied to numerous practical problems in pattern classification. It is a rule of thumb that more complex tasks require larger networks. However, the design of optimal network architectures for specific tasks is still an unsolved fundamental problem. In this study, we consider three-layered neural networks for memorizing binary patterns. We developed a new complexity measure of binary patterns, and estimated the minimal network size for memorizing them as a function of their complexity. We formulated the minimal network size for regular, random, and complex patterns. In particular, the minimal size for complex patterns, which are neither ordered nor disordered, was predicted by measuring their Hamming distances from known ordered patterns. Our predictions agree with simulations based on the back-propagation algorithm. (C) 2016 Elsevier B.V. All rights reserved.
C1 [Pastor, Marissa; Song, Juyong; Danh-Tai Hoang; Jo, Junghyo] Asia Pacific Ctr Theoret Phys, Pohang, South Korea.
[Pastor, Marissa] Univ San Carlos Talamban, Dept Phys, Cebu, Philippines.
[Song, Juyong; Jo, Junghyo] Pohang Univ Sci & Technol, Dept Phys, Pohang, South Korea.
[Danh-Tai Hoang] Quang Binh Univ, Dept Nat Sci, Dong Hoi, Vietnam.
[Danh-Tai Hoang] NIDDK, Lab Biol Modeling, NIH, Bethesda, MD 20892 USA.
RP Jo, J (reprint author), Asia Pacific Ctr Theoret Phys, Pohang, South Korea.
EM jojunghyo@apctp.org
FU Basic Science Research Program through the National Foundation of Korea
funded by the Ministry of Science, ICT & Future Planning
[2013R1A1A1006655]; Max Planck Society; Korea Ministry of Education,
Science and Technology, Gyeongsangbuk-Do and Pohang City
FX We thank V. Periwal for discussions and hospitality during our stay at
National Institutes of Health in the US. M. Pastor acknowledges the
Office of Research, University of San Carlos, Cebu City, Philippines.
This research was supported by Basic Science Research Program through
the National Foundation of Korea funded by the Ministry of Science, ICT
& Future Planning (No. 2013R1A1A1006655) and by the Max Planck Society,
the Korea Ministry of Education, Science and Technology,
Gyeongsangbuk-Do and Pohang City.
NR 23
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Z9 0
U1 9
U2 9
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0378-4371
EI 1873-2119
J9 PHYSICA A
JI Physica A
PD NOV 15
PY 2016
VL 462
BP 31
EP 37
DI 10.1016/j.physa.2016.06.025
PG 7
WC Physics, Multidisciplinary
SC Physics
GA DT9SF
UT WOS:000381841900004
ER
PT J
AU Gobl, C
Resch, M
Strickland, M
Hartlmuller, C
Viertler, M
Tjandra, N
Madl, T
AF Goebl, Christoph
Resch, Moritz
Strickland, Madeleine
Hartlmueller, Christoph
Viertler, Martin
Tjandra, Nico
Madl, Tobias
TI Increasing the Chemical-Shift Dispersion of Unstructured Proteins with a
Covalent Lanthanide Shift Reagent
SO ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
LA English
DT Article
DE chemical-shift dispersion; intrinsically disordered proteins;
lanthanides; NMR; pseudo-contact shifts
ID INTRINSICALLY DISORDERED PROTEINS; BACKBONE RESONANCE ASSIGNMENT;
NMR-SPECTROSCOPY; UNFOLDED PROTEINS; BIOMOLECULAR NMR; LOW-COMPLEXITY;
REGIONS; BINDING; FUS; TRANSPORTIN
AB The study of intrinsically disordered proteins (IDPs) by NMR often suffers from highly overlapped resonances that prevent unambiguous chemical-shift assignments, and data analysis that relies on well-separated resonances. We present a covalent paramagnetic lanthanide-binding tag (LBT) for increasing the chemical-shift dispersion and facilitating the chemical-shift assignment of challenging, repeat-containing IDPs. Linkage of the DOTA-based LBT to a cysteine residue induces pseudo-contact shifts (PCS) for resonances more than 20 residues from the spin-labeling site. This leads to increased chemical-shift dispersion and decreased signal overlap, thereby greatly facilitating chemical-shift assignment. This approach is applicable to IDPs of varying sizes and complexity, and is particularly helpful for repeat-containing IDPs and low-complexity regions. This results in improved efficiency for IDP analysis and binding studies.
C1 [Goebl, Christoph; Resch, Moritz; Strickland, Madeleine; Hartlmueller, Christoph; Viertler, Martin; Tjandra, Nico; Madl, Tobias] Tech Univ Munich, Ctr Integrated Prot Sci Munich, Dept Chem, Lichtenbergstr 4, D-85748 Garching, Germany.
[Goebl, Christoph; Resch, Moritz; Hartlmueller, Christoph; Viertler, Martin; Madl, Tobias] Helmholtz Zentrum Munchen, Inst Biol Struct, Ingolstadter Landstr 1, D-85764 Neuherberg, Germany.
[Madl, Tobias] Med Univ Graz, Ctr Mol Med, Inst Mol Biol & Biochem, A-8010 Graz, Austria.
[Strickland, Madeleine; Tjandra, Nico] NHLBI, Lab Struct Biophys, Biochem & Biophys Ctr, NIH, Bldg 50, Bethesda, MD 20814 USA.
RP Tjandra, N; Madl, T (reprint author), Tech Univ Munich, Ctr Integrated Prot Sci Munich, Dept Chem, Lichtenbergstr 4, D-85748 Garching, Germany.; Madl, T (reprint author), Helmholtz Zentrum Munchen, Inst Biol Struct, Ingolstadter Landstr 1, D-85764 Neuherberg, Germany.; Madl, T (reprint author), Med Univ Graz, Ctr Mol Med, Inst Mol Biol & Biochem, A-8010 Graz, Austria.
EM tjandran@nhlbi.nih.gov; tobias.madl@medunigraz.at
RI Madl, Tobias/B-1682-2012; Goebl, Christoph/G-7578-2016;
OI Madl, Tobias/0000-0002-9725-5231; Gobl, Christoph/0000-0001-8614-1434;
Strickland, Madeleine/0000-0001-8160-070X; Resch,
Moritz/0000-0003-3477-3565
FU Intramural Research Program of the NIH, NHLBI; Bavarian Ministry of
Sciences, Research and the Arts (Bavarian Molecular Biosystems Research
Network); German Research Foundation (Emmy Noether program) [MA
5703/1-1]; Center for Integrated Protein Science Munich (CIPSM);
Austrian Science Fund [FWF: P28854, W1226-B18]
FX Part of this work was supported by the Intramural Research Program of
the NIH, NHLBI. T.M. was supported by the Bavarian Ministry of Sciences,
Research and the Arts (Bavarian Molecular Biosystems Research Network),
the German Research Foundation (Emmy Noether program MA 5703/1-1), the
Center for Integrated Protein Science Munich (CIPSM), and the Austrian
Science Fund (FWF: P28854, W1226-B18). We thank the Imaging Probe
Development Group of the NIH for synthesizing the Yb-M8 tag. Critical
reading of the manuscript by Ashley C. Barnes, Sam Asami, and Vanessa
Morris is gratefully acknowledged.
NR 48
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U1 3
U2 3
PU WILEY-V C H VERLAG GMBH
PI WEINHEIM
PA POSTFACH 101161, 69451 WEINHEIM, GERMANY
SN 1433-7851
EI 1521-3773
J9 ANGEW CHEM INT EDIT
JI Angew. Chem.-Int. Edit.
PD NOV 14
PY 2016
VL 55
IS 47
BP 14847
EP 14851
DI 10.1002/anie.201607261
PG 5
WC Chemistry, Multidisciplinary
SC Chemistry
GA EC6NH
UT WOS:000388252700067
PM 27763708
ER
PT J
AU Weeraratna, AT
Gorospe, M
AF Weeraratna, Ashani T.
Gorospe, Myriam
TI UNRelenting Translation UNRestrains Melanoma Migration
SO CANCER CELL
LA English
DT Editorial Material
ID EXPRESSION; PROTEINS; CELLS; UNR
AB The cytoplasmic RNA-binding protein UNR influences key developmental processes by controlling mRNA turnover and translation initiation. In this issue of Cancer Cell, Wurth et al. report that UNR is highly expressed in melanoma and enhances invasion and metastasis at least partly by inducing translation elongation of VIM and RAC1 mRNAs.
C1 [Weeraratna, Ashani T.] Wistar Inst Anat & Biol, Tumor Microenvironm & Metastasis Program, 3601 Spruce St, Philadelphia, PA 19104 USA.
[Gorospe, Myriam] NIA, Lab Genet & Genom, IRP, NIH, Baltimore, MD 21224 USA.
RP Gorospe, M (reprint author), NIA, Lab Genet & Genom, IRP, NIH, Baltimore, MD 21224 USA.
EM myriam-gorospe@nih.gov
FU NCI NIH HHS [P30 CA010815, R01 CA174746]
NR 10
TC 0
Z9 0
U1 3
U2 3
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1535-6108
EI 1878-3686
J9 CANCER CELL
JI Cancer Cell
PD NOV 14
PY 2016
VL 30
IS 5
BP 655
EP 657
DI 10.1016/j.ccell.2016.10.012
PG 3
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA EC3ZE
UT WOS:000388064800002
PM 27846383
ER
PT J
AU Ceribelli, M
Hou, ZE
Kelly, PN
Huang, DW
Wright, G
Ganapathi, K
Evbuomwan, MO
Pittaluga, S
Shaffer, AL
Marcucci, G
Forman, SJ
Xiao, WM
Guha, R
Zhang, XH
Ferrer, M
Chaperot, L
Plumas, J
Jaffe, ES
Thomas, CJ
Reizis, B
Staudt, LM
AF Ceribelli, Michele
Hou, Zhiying Esther
Kelly, Priscilla N.
Huang, Da Wei
Wright, George
Ganapathi, Karthik
Evbuomwan, Moses O.
Pittaluga, Stefania
Shaffer, Arthur L.
Marcucci, Guido
Forman, Stephen J.
Xiao, Wenming
Guha, Rajarshi
Zhang, Xiaohu
Ferrer, Marc
Chaperot, Laurence
Plumas, Joel
Jaffe, Elaine S.
Thomas, Craig J.
Reizis, Boris
Staudt, Louis M.
TI A Druggable TCF4-and BRD4-Dependent Transcriptional Network Sustains
Malignancy in Blastic Plasmacytoid Dendritic Cell Neoplasm
SO CANCER CELL
LA English
DT Article
ID INTERFERON-PRODUCING CELLS; SELECTIVE-INHIBITION; SEQUENCING REVEALS;
FACTOR E2-2; SPI-B; LYMPHOMA; EXPRESSION; MUTATIONS; CANCER; RECURRENT
AB Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is an aggressive and largely incurable hematologic malignancy originating from plasmacytoid dendritic cells (pDCs). Using RNAi screening, we identified the E-box transcription factor TCF4 as a master regulator of the BPDCN oncogenic program. TCF4 served as a faithful diagnostic marker of BPDCN, and its downregulation caused the loss of the BPDCN-specific gene expression program and apoptosis. High-throughput drug screening revealed that bromodomain and extra-terminal domain inhibitors (BETis) induced BPDCN apoptosis, which was attributable to disruption of a BPDCN-specific transcriptional network controlled by TCF4-dependent super-enhancers. BETis retarded the growth of BPDCN xenografts, supporting their clinical evaluation in this recalcitrant malignancy.
C1 [Ceribelli, Michele; Kelly, Priscilla N.; Huang, Da Wei; Shaffer, Arthur L.; Staudt, Louis M.] NCI, Lymphoid Malignancies Branch, NIH, Bethesda, MD 20892 USA.
[Hou, Zhiying Esther; Reizis, Boris] Columbia Univ, Med Ctr, Dept Microbiol & Immunol, New York, NY 10032 USA.
[Wright, George] NCI, Biometr Res Branch, NIH, Bethesda, MD 20892 USA.
[Ganapathi, Karthik; Evbuomwan, Moses O.; Pittaluga, Stefania; Jaffe, Elaine S.] NCI, Pathol Lab, NIH, Bldg 10, Bethesda, MD 20892 USA.
[Marcucci, Guido; Forman, Stephen J.] City Hope Natl Med Ctr, Dept Hematol & Hematopoiet Cell Transplant, 1500 E Duarte Rd, Duarte, CA 91010 USA.
[Xiao, Wenming] NCTR FDA, Div Bioinformat & Biostat, Jefferson, AR 72079 USA.
[Guha, Rajarshi; Zhang, Xiaohu; Ferrer, Marc; Thomas, Craig J.] NIH, Div Preclin Innovat, Natl Ctr Adv Translat Sci, Bldg 10, Bethesda, MD 20892 USA.
[Chaperot, Laurence; Plumas, Joel] EFS Rhone Alpes Grenoble, R&D Lab, F-38701 La Tronche, France.
[Chaperot, Laurence; Plumas, Joel] CNRS, INSERM, Inst Adv Biosci UGA, U1209,UMR 5309, F-38000 Grenoble, France.
[Reizis, Boris] NYU, Sch Med, Dept Pathol, New York, NY 10016 USA.
[Ganapathi, Karthik] Columbia Univ, Dept Pathol & Cell Biol, New York, NY 10032 USA.
RP Staudt, LM (reprint author), NCI, Lymphoid Malignancies Branch, NIH, Bethesda, MD 20892 USA.; Reizis, B (reprint author), Columbia Univ, Med Ctr, Dept Microbiol & Immunol, New York, NY 10032 USA.; Reizis, B (reprint author), NYU, Sch Med, Dept Pathol, New York, NY 10016 USA.
EM boris.reizis@nyumc.org; lstaudt@mail.nih.gov
OI Reizis, Boris/0000-0003-1140-7853
FU NIH, National Cancer Institute, Center for Cancer Research; National
Human Genome Research Institute; Frederick National Laboratory for
Cancer Research, NIH [HHSN261200800001E, U54CA143930]; Division of
Preclinical Innovation, National Center for Advancing Translational
Sciences; Molecular Libraries Initiative of the NIH Roadmap for Medical
Research; NIH [AI072571]; Feinberg Lymphoma Research Pilot award
FX This research was supported by the Intramural Research Programs of the
NIH, National Cancer Institute, Center for Cancer Research, and the
National Human Genome Research Institute; the Frederick National
Laboratory for Cancer Research, NIH including contract HHSN261200800001E
and grant #U54CA143930; the Division of Preclinical Innovation, National
Center for Advancing Translational Sciences; the Molecular Libraries
Initiative of the NIH Roadmap for Medical Research; and by NIH grant
AI072571 and the Feinberg Lymphoma Research Pilot award to B.R. We thank
Kathleen Meyer for help with the GEO submission.
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PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1535-6108
EI 1878-3686
J9 CANCER CELL
JI Cancer Cell
PD NOV 14
PY 2016
VL 30
IS 5
BP 764
EP 778
DI 10.1016/j.ccell.2016.10.002
PG 15
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA EC3ZE
UT WOS:000388064800015
PM 27846392
ER
PT J
AU Queiros, AC
Beekman, R
Vilarrasa-Blasi, R
Duran-Ferrer, M
Clot, G
Merkel, A
Raineri, E
Russinol, N
Castellano, G
Bea, S
Navarro, A
Kulis, M
Verdaguer-Dot, N
Jares, P
Enjuanes, A
Calasanz, MJ
Bergmann, A
Vater, I
Salaverria, I
van de Werken, HJG
Wilson, WH
Datta, A
Flicek, P
Royo, R
Martens, J
Gine, E
Lopez-Guillermo, A
Stunnenberg, HG
Klapper, W
Pott, C
Heath, S
Gut, IG
Siebert, R
Campo, E
Martin-Subero, JI
AF Queiros, Ana C.
Beekman, Renee
Vilarrasa-Blasi, Roser
Duran-Ferrer, Marti
Clot, Guillem
Merkel, Angelika
Raineri, Emanuele
Russinol, Nuria
Castellano, Giancarlo
Bea, Silvia
Navarro, Alba
Kulis, Marta
Verdaguer-Dot, Nuria
Jares, Pedro
Enjuanes, Anna
Jose Calasanz, Maria
Bergmann, Anke
Vater, Inga
Salaverria, Itziar
van de Werken, Harmen J. G.
Wilson, Wyndham H.
Datta, Avik
Flicek, Paul
Royo, Romina
Martens, Joost
Gine, Eva
Lopez-Guillermo, Armando
Stunnenberg, Hendrik G.
Klapper, Wolfram
Pott, Christiane
Heath, Simon
Gut, Ivo G.
Siebert, Reiner
Campo, Elias
Martin-Subero, Jose I.
TI Decoding the DNA Methylome of Mantle Cell Lymphoma in the Light of the
Entire B Cell Lineage
SO CANCER CELL
LA English
DT Article
ID CHRONIC LYMPHOCYTIC-LEUKEMIA; MOLECULAR PATHOGENESIS; CANCER-CELLS;
METHYLATION; MUTATIONS; ENHANCERS; EPIGENOME; REVEALS; GENOME;
DIFFERENTIATION
AB We analyzed the in silico purified DNA methylation signatures of 82 mantle cell lymphomas (MCL) in comparison with cell subpopulations spanning the entire B cell lineage. We identified two MCL subgroups, respectively carrying epigenetic imprints of germinal-center-inexperienced and germinal-center-experienced B cells, and we found that DNA methylation profiles during lymphomagenesis are largely influenced by the methylation dynamics in normal B cells. An integrative epigenomic approach revealed 10,504 differentially methylated regions in regulatory elements marked by H3K27ac in MCL primary cases, including a distant enhancer showing de novo looping to the MCL oncogene SOX11. Finally, we observed that the magnitude of DNA methylation changes per case is highly variable and serves as an independent prognostic factor for MCL outcome.
C1 [Queiros, Ana C.; Vilarrasa-Blasi, Roser; Duran-Ferrer, Marti; Russinol, Nuria; Kulis, Marta; Verdaguer-Dot, Nuria; Jares, Pedro; Campo, Elias; Martin-Subero, Jose I.] Univ Barcelona, Dept Fundamentos Clin, E-08036 Barcelona, Spain.
[Beekman, Renee; Clot, Guillem; Russinol, Nuria; Castellano, Giancarlo; Bea, Silvia; Navarro, Alba; Verdaguer-Dot, Nuria; Salaverria, Itziar; Campo, Elias; Martin-Subero, Jose I.] Inst Invest Biomed August Pi & Sunyer IDIBAPS, Barcelona 08036, Spain.
[Merkel, Angelika; Raineri, Emanuele; Heath, Simon; Gut, Ivo G.] Ctr Nacl Anal Genom, Parc Cient Barcelona, Barcelona 08028, Spain.
[Jares, Pedro; Enjuanes, Anna] IDIBAPS, Unidad Genom, Barcelona 08036, Spain.
[Jose Calasanz, Maria] Univ Navarra, Dept Genet, Pamplona 31008, Spain.
[Bergmann, Anke; Vater, Inga; Siebert, Reiner] Univ Kiel, Inst Human Genet, D-24105 Kiel, Germany.
[Bergmann, Anke] Univ Kiel, Dept Pediat, D-24105 Kiel, Germany.
[Bergmann, Anke] Univ Hosp Schleswig Holstein, D-24105 Kiel, Germany.
[van de Werken, Harmen J. G.] Erasmus MC, Dept Cell Biol, NL-3015 CN Rotterdam, Netherlands.
[van de Werken, Harmen J. G.] Erasmus MC, Canc Computat Biol Ctr, NL-3015 CN Rotterdam, Netherlands.
[van de Werken, Harmen J. G.] Erasmus MC, Dept Urol, NL-3015 CN Rotterdam, Netherlands.
[Wilson, Wyndham H.] NCI, Lymphoid Malignancies Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Datta, Avik; Flicek, Paul] EBI, EMBL, Wellcome Trust Genome Campus, Hinxton CB10 1SD, England.
[Royo, Romina] BSC, Joint Program Computat Biol, Barcelona Sci Pk, Barcelona 08034, Spain.
[Royo, Romina] IRB, Barcelona Sci Pk, Barcelona 08034, Spain.
[Martens, Joost; Stunnenberg, Hendrik G.] Radboud Univ Nijmegen, FNWI, NCMLS, Mol Biol, NL-6500 HB Nijmegen, Netherlands.
[Gine, Eva; Lopez-Guillermo, Armando] IDIBAPS, Hosp Clin, Serv Hematol, Barcelona 08036, Spain.
[Klapper, Wolfram] Christian Albrecht Univ, Hematopathol Sect, D-24105 Kiel, Germany.
[Klapper, Wolfram] Christian Albrecht Univ, Lymph Node Registry, D-24105 Kiel, Germany.
[Pott, Christiane] Univ Hosp Schleswig Holstein, Dept Med 2, D-24116 Kiel, Germany.
[Campo, Elias] Hosp Clin Barcelona, Serv Anat Patol, Unidad Hematopatol, E-08036 Barcelona, Spain.
RP Martin-Subero, JI (reprint author), Univ Barcelona, Dept Fundamentos Clin, E-08036 Barcelona, Spain.; Martin-Subero, JI (reprint author), Inst Invest Biomed August Pi & Sunyer IDIBAPS, Barcelona 08036, Spain.
EM imartins@clinic.ub.es
RI Klapper, Wolfram/S-6314-2016; Siebert, Reiner/A-8049-2010;
OI Beekman, Renee/0000-0001-7081-7874; Flicek, Paul/0000-0002-3897-7955;
van de Werken, Harmen/0000-0002-9794-1477
FU European Union through the Blueprint Consortium [282510]; European
Hematology Association; Worldwide Cancer Research [16-1285]; Spanish
Ministerio de Economia y Competitividad (MINECO) [SAF2015-64885-R];
Generalitat de Catalunya Suport Grups de Recerca AGAUR [2014-SGR-795];
Portuguese Fundacao para a Ciencia e a Tecnologia (FCT); Netherlands
Organisation for Scientific Research (NWO); EU (Marie Curie); MINECO
FX This work was funded by the European Union's Seventh Framework Program
through the Blueprint Consortium (grant agreement 282510), the European
Hematology Association (Non-Clinical Advanced Research Fellowships to
J.I.M.-S.), the Worldwide Cancer Research (grant number 16-1285, to
J.I.M.-S.), Spanish Ministerio de Economia y Competitividad (MINECO),
grant no. SAF2015-64885-R (to E.C.) and Generalitat de Catalunya Suport
Grups de Recerca AGAUR 2014-SGR-795 (to E.C.). Methylation microarrays
were out-sourced to the Spanish Centro Nacional de Genotipado
(CEGEN-ISCIII). We are indebted to the Genomics core facility of the
Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS) for
technical help. This work was partially developed at the Centro Esther
Koplowitz (CEK; Barcelona, Spain). J.I.M.-S. is a Ramon y Cajal
researcher of MINECO, E.C. is an Academia Researcher of the "Institucio
Catalana de Recerca i Estudis Avancats" (ICREA) of the Generalitat de
Catalunya, A.C.Q. is supported by a Portuguese Fundacao para a Ciencia e
a Tecnologia (FCT) fellowship, R.B. by fellowships from the Netherlands
Organisation for Scientific Research (NWO) and the EU (Marie Curie), and
R.V.-B by a pre-doctoral fellowship of the MINECO. Paul Flicek is a
member of the Scientific Advisory Board for Omicia, Inc.
NR 52
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PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1535-6108
EI 1878-3686
J9 CANCER CELL
JI Cancer Cell
PD NOV 14
PY 2016
VL 30
IS 5
BP 806
EP 821
DI 10.1016/j.ccell.2016.09.014
PG 16
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA EC3ZE
UT WOS:000388064800018
PM 27846393
ER
PT J
AU Luo, ZP
AF Luo, Zhipu
TI Selenourea: a convenient phasing vehicle for macromolecular X-ray
crystal structures
SO SCIENTIFIC REPORTS
LA English
DT Article
ID ANOMALOUS DIFFRACTION; CRYSTALLOGRAPHY; PROTEINS; SIGNAL; DNA;
DERIVATIZATION; SULFUR; MAD
AB Majority of novel X-ray crystal structures of proteins are currently solved using the anomalous diffraction signal provided by selenium after incorporation of selenomethionine instead of natural methionine by genetic engineering methods. However, selenium can be inserted into protein crystals in the form of selenourea (SeC(NH2)(2)), by adding the crystalline powder of selenourea into mother liquor or cryo-solution with native crystals, in analogy to the classic procedure of heavy-atom derivatization. Selenourea is able to bind to reactive groups at the surface of macromolecules primarily through hydrogen bonds, where the selenium atom may serve as acceptor and amide groups as donors. Selenourea has different chemical properties than heavy-atom reagents and halide ions and provides a convenient way of phasing crystal structures of macromolecules.
C1 [Luo, Zhipu] Argonne Natl Lab, Natl Canc Inst, Synchrotron Radiat Res Sect, 9700 S Cass Ave, Argonne, IL 60439 USA.
RP Luo, ZP (reprint author), Argonne Natl Lab, Natl Canc Inst, Synchrotron Radiat Res Sect, 9700 S Cass Ave, Argonne, IL 60439 USA.
EM luozhipu@anl.gov
FU Intramural Research Program of the National Cancer Institute
FX This work was supported by the Intramural Research Program of the
National Cancer Institute. The help of Zbigniew Dauter in preparation of
this manuscript is gratefully appreciated. The instruction for CFP
expression and purification and growth of HPP crystals by Milosz
Ruszkowski are appreciated. Provision of thaumatin and trypsin crystals
by Miroslawa Dauter is gratefully acknowledged.
NR 29
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U1 3
U2 3
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2045-2322
J9 SCI REP-UK
JI Sci Rep
PD NOV 14
PY 2016
VL 6
AR 37123
DI 10.1038/srep37123
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EC1GJ
UT WOS:000387852600001
PM 27841370
ER
PT J
AU Greer, RL
Dong, XX
Moraes, ACF
Zielke, RA
Fernandes, GR
Peremyslova, E
Vasquez-Perez, S
Schoenborn, AA
Gomes, EP
Pereira, AC
Ferreira, SRG
Yao, M
Fuss, IJ
Strober, W
Sikora, AE
Taylor, GA
Gulati, AS
Morgun, A
Shulzhenko, N
AF Greer, Renee L.
Dong, Xiaoxi
Moraes, Ana Carolina F.
Zielke, Ryszard A.
Fernandes, Gabriel R.
Peremyslova, Ekaterina
Vasquez-Perez, Stephany
Schoenborn, Alexi A.
Gomes, Everton P.
Pereira, Alexandre C.
Ferreira, Sandra R. G.
Yao, Michael
Fuss, Ivan J.
Strober, Warren
Sikora, Aleksandra E.
Taylor, Gregory A.
Gulati, Ajay S.
Morgun, Andrey
Shulzhenko, Natalia
TI Akkermansia muciniphila mediates negative effects of IFN gamma on
glucose metabolism
SO NATURE COMMUNICATIONS
LA English
DT Article
ID COMMON VARIABLE IMMUNODEFICIENCY; DIET-INDUCED OBESITY; GUT MICROBIOTA;
INTERFERON-GAMMA; ADIPOSE-TISSUE; BODY-WEIGHT; ADAPTIVE IMMUNITY; MICE
LACKING; T-CELLS; INFLAMMATION
AB Cross-talk between the gut microbiota and the host immune system regulates host metabolism, and its dysregulation can cause metabolic disease. Here, we show that the gut microbe Akkermansia muciniphila can mediate negative effects of IFN gamma on glucose tolerance. In IFN gamma-deficient mice, A. muciniphila is significantly increased and restoration of IFN gamma levels reduces A. muciniphila abundance. We further show that IFN gamma-knockout mice whose microbiota does not contain A. muciniphila do not show improvement in glucose tolerance and adding back A. muciniphila promoted enhanced glucose tolerance. We go on to identify Irgm1 as an IFN gamma-regulated gene in the mouse ileum that controls gut A. muciniphila levels. A. muciniphila is also linked to IFN gamma-regulated gene expression in the intestine and glucose parameters in humans, suggesting that this trialogue between IFN gamma, A. muciniphila and glucose tolerance might be an evolutionally conserved mechanism regulating metabolic health in mice and humans.
C1 [Greer, Renee L.; Vasquez-Perez, Stephany; Shulzhenko, Natalia] Oregon State Univ, Coll Vet Med, 105 Dryden Hall,450 SW 30th St, Corvallis, OR 97331 USA.
[Dong, Xiaoxi; Zielke, Ryszard A.; Peremyslova, Ekaterina; Sikora, Aleksandra E.; Morgun, Andrey] Oregon State Univ, Coll Pharm, 1601 SW Jefferson Way, Corvallis, OR 97331 USA.
[Moraes, Ana Carolina F.; Ferreira, Sandra R. G.] Univ Sao Paulo, Sch Publ Hlth, Dept Epidemiol, Ave Dr Arnaldo 715, BR-01246904 Sao Paulo, SP, Brazil.
[Fernandes, Gabriel R.] Fundacao Oswaldo Cruz, Rene Rachou Res Ctr, Ave Augusto de Lima 1715, BR-30190002 Belo Horizonte, MG, Brazil.
[Schoenborn, Alexi A.; Gulati, Ajay S.] Univ N Carolina, Div Pediat Gastroenterol, 260 MacNider Bldg,CB 7220, Chapel Hill, NC 27599 USA.
[Gomes, Everton P.; Pereira, Alexandre C.] Univ Sao Paulo, Sch Med, Heart Inst InCor, Lab Genet & Mol Cardiol, Ave Dr Eneas de Carvalho Aguiar,44, BR-05403000 Sao Paulo, SP, Brazil.
[Yao, Michael; Fuss, Ivan J.; Strober, Warren] NIAID, Mucosal Immun Sect, Lab Immune Def, Bethesda, MD 20892 USA.
[Taylor, Gregory A.] Duke Univ, Med Ctr, Geriatr Res Educ & Clin Ctr, VA Med Ctr,Dept Med,Div Geriatr, Duke Box 3003, Durham, NC 27710 USA.
[Taylor, Gregory A.] Duke Univ, Med Ctr, Geriatr Res Educ & Clin Ctr, VA Med Ctr,Dept Mol Genet,Div Geriatr, Duke Box 3003, Durham, NC 27710 USA.
[Taylor, Gregory A.] Duke Univ, Med Ctr, Geriatr Res Educ & Clin Ctr, VA Med Ctr,Dept Microbiol & Immunol,Div Geriatr, Duke Box 3003, Durham, NC 27710 USA.
[Taylor, Gregory A.] Duke Univ, Med Ctr, Ctr Study Aging & Human Dev, Duke Box 3003, Durham, NC 27710 USA.
RP Shulzhenko, N (reprint author), Oregon State Univ, Coll Vet Med, 105 Dryden Hall,450 SW 30th St, Corvallis, OR 97331 USA.; Morgun, A (reprint author), Oregon State Univ, Coll Pharm, 1601 SW Jefferson Way, Corvallis, OR 97331 USA.
EM anemorgun@hotmail.com; natalia.shulzhenko@oregonstate.edu
FU Oregon State University (OSU), USA [NIH U01 AI109695, R01 DK103761];
Intramural Research Program of the NIH, NIAID; FAPESP (Sao Paulo
Research Foundation) of ADVENTO Study [12/12626-9, 12/03880-9]
FX This research was supported by startup funds for AM and NS from Oregon
State University (OSU), USA; NIH U01 AI109695 (AM) and R01 DK103761 (NS)
and by the Intramural Research Program of the NIH, NIAID (MY, IJF, WS).
We also thank the FAPESP (Sao Paulo Research Foundation) for financial
support (12/12626-9 and 12/03880-9) of ADVENTO Study. We thank Oregon
State University Center for Genome Research and Biocomputing (CGRB) for
sequencing services and technical support; Dr Daniel Cawley and the
Oregon Health and Science University Monoclonal Antibody Core for
production of IFN gamma antibodies; and the personnel of Oregon State
University Laboratory Animal Resources Center.
NR 68
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U1 20
U2 20
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2041-1723
J9 NAT COMMUN
JI Nat. Commun.
PD NOV 14
PY 2016
VL 7
AR 13329
DI 10.1038/ncomms13329
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EB7IF
UT WOS:000387559600001
PM 27841267
ER
PT J
AU Iranzo, J
Buldu, JM
Aguirre, J
AF Iranzo, Jaime
Buldu, Javier M.
Aguirre, Jacobo
TI Competition among networks highlights the power of the weak
SO NATURE COMMUNICATIONS
LA English
DT Article
ID COMPLEX NETWORKS; EVOLUTIONARY GAMES; SOCIAL NETWORKS; DYNAMICS;
COOPERATION
AB The unpreventable connections between real networked systems have recently called for an examination of percolation, diffusion or synchronization phenomena in multilayer networks. Here we use network science and game theory to explore interactions in networks-of-networks and model these as a game for gaining importance. We propose a viewpoint where networks choose the connection strategies, in contrast with classical approaches where nodes are the active players. Specifically, we investigate how creating paths between networks leads to different Nash equilibria that determine their structural and dynamical properties. In a wide variety of cases, selecting adequate connections leads to a cooperative solution that allows weak networks to overcome the strongest opponent. Counterintuitively, each weak network can induce a global transition to such cooperative configuration regardless of the actions of the strongest network. This power of the weak reveals a critical dominance of the underdogs in the fate of networks-of-networks.
C1 [Iranzo, Jaime] Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA.
[Buldu, Javier M.] Ctr Biomed Technol UPM, Lab Biol Networks, Madrid 28223, Spain.
[Buldu, Javier M.] Univ Rey Juan Carlos, Complex Syst Grp, Madrid 28933, Spain.
[Buldu, Javier M.; Aguirre, Jacobo] GISC, Madrid, Spain.
[Aguirre, Jacobo] CSIC, Ctr Nacl Biotecnol, C Darwin 3, E-28049 Madrid, Spain.
RP Aguirre, J (reprint author), GISC, Madrid, Spain.; Aguirre, J (reprint author), CSIC, Ctr Nacl Biotecnol, C Darwin 3, E-28049 Madrid, Spain.
EM jaguirre@cnb.csic.es
RI Iranzo, Jaime/H-5197-2011
OI Iranzo, Jaime/0000-0002-4538-7726
FU Spanish MINECO [FIS2011-27569, FIS2014-57686, FIS2013-41057]; intramural
funds of the US Department of Health and Human Services
FX We thank S. Ahnert, A. Arenas, S. Boccaletti, D. Crespo, J. Cuesta, L.
Dudbridge, J. Garcia-Ojalvo, S. Manrubia, Y. Moreno, F. Pablo-Marti, D.
Papo, M.A. Porter, F. Puente-Sanchez, A. Sanchez and A. Sanz for
fruitful conversations, and J.F. Nash for being a source of inspiration.
J. A. acknowledges financial support from Spanish MINECO (projects
FIS2011-27569 and FIS2014-57686), J. I. is supported by intramural funds
of the US Department of Health and Human Services (to the National
Library of Medicine) and J.M.B. is funded by Spanish MINECO (project
FIS2013-41057).
NR 44
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U1 9
U2 9
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2041-1723
J9 NAT COMMUN
JI Nat. Commun.
PD NOV 14
PY 2016
VL 7
AR 13273
DI 10.1038/ncomms13273
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EB7IA
UT WOS:000387559100001
PM 27841258
ER
PT J
AU Molina, O
Vargiu, G
Abad, MA
Zhiteneva, A
Jeyaprakash, AA
Masumoto, H
Kouprina, N
Larionov, V
Earnshaw, WC
AF Molina, Oscar
Vargiu, Giulia
Abad, Maria Alba
Zhiteneva, Alisa
Jeyaprakash, A. Arockia
Masumoto, Hiroshi
Kouprina, Natalay
Larionov, Vladimir
Earnshaw, William C.
TI Epigenetic engineering reveals a balance between histone modifications
and transcription in kinetochore maintenance
SO NATURE COMMUNICATIONS
LA English
DT Article
ID CENP-A; CHROMOSOME SEGREGATION; CENTROMERIC CHROMATIN; H3; DOMAIN; RNA;
ORGANIZATION; NUCLEOSOMES; ACETYLATION; COMPONENT
AB Centromeres consist of specialized centrochromatin containing CENP-A nucleosomes intermingled with H3 nucleosomes carrying transcription-associated modifications. We have designed a novel synthetic biology 'in situ epistasis' analysis in which H3 dimethylated on lysine 4 (H3K4me2) demethylase LSD2 plus synthetic modules with competing activities are simultaneously targeted to a synthetic alphoid(tetO) HAC centromere. This allows us to uncouple transcription from histone modifications at the centromere. Here, we report that H3K4me2 loss decreases centromeric transcription, CENP-A assembly and stability and causes spreading of H3K9me3 across the HAC, ultimately inactivating the centromere. Surprisingly, CENP-28/Eaf6-induced transcription of the alphoidtetO array associated with H4K12 acetylation does not rescue the phenotype, whereas p65-induced transcription associated with H3K9 acetylation does rescue. Thus mitotic transcription plus histone modifications including H3K9ac constitute the 'epigenetic landscape' allowing CENP-A assembly and centrochromatin maintenance. H3K4me2 is required for the transcription and H3K9ac may form a barrier to prevent heterochromatin spreading and kinetochore inactivation at human centromeres.
C1 [Molina, Oscar; Vargiu, Giulia; Abad, Maria Alba; Zhiteneva, Alisa; Jeyaprakash, A. Arockia; Earnshaw, William C.] Univ Edinburgh, Wellcome Trust Ctr Cell Biol, Edinburgh EH9 3QR, Midlothian, Scotland.
[Masumoto, Hiroshi] Kazusa DNA Res Inst, Lab Cell Engn, Dept Frontier Res, Kisarazu 2920818, Japan.
[Kouprina, Natalay; Larionov, Vladimir] NCI, Genome Struct & Funct Grp, Dev Therapeut Branch, NIH, Bethesda, MD 20892 USA.
RP Earnshaw, WC (reprint author), Univ Edinburgh, Wellcome Trust Ctr Cell Biol, Edinburgh EH9 3QR, Midlothian, Scotland.
EM bill.earnshaw@ed.ac.uk
OI Arulanandam, Arockia Jeyaprakash/0000-0002-1889-8635
FU European Molecular Biology Organization (long-term EMBO fellowship)
[ALTF-453-2012]; Wellcome Trust [073915]; Intramural Research Program of
the NIH, NCI Center for Cancer Research; MEXT KAKENHI grant [23247030,
23114008]; Kazusa DNA Research Institute Foundation; Career development
grant [095822]; Marie Curie career integration grant [334291]; Wellcome
Trust Centre for Cell Biology [077707, 092076]
FX We thank Drs Patrick Heun, Pauline Audergon, Manu Shukla and Dan Booth
for critical discussions and feedback on the manuscript. O.M. was funded
by the European Molecular Biology Organization (long-term EMBO
fellowship; ALTF-453-2012). This work was funded by the Wellcome Trust,
of which W.C.E. is a Principal Research Fellow (grant number 073915),
the Intramural Research Program of the NIH, NCI Center for Cancer
Research (V.L. and N.K.) and MEXT KAKENHI grant numbers 23247030,
23114008 and the Kazusa DNA Research Institute Foundation (H.M.). Career
development grant 095822 and Marie Curie career integration grant 334291
(A.A.J.). The Wellcome Trust Centre for Cell Biology is supported by
core grant numbers 077707 and 092076.
NR 65
TC 1
Z9 1
U1 9
U2 9
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2041-1723
J9 NAT COMMUN
JI Nat. Commun.
PD NOV 14
PY 2016
VL 7
AR 13334
DI 10.1038/ncomms13334
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EB7IH
UT WOS:000387559800001
PM 27841270
ER
PT J
AU Janakiram, NB
Mohammed, A
Bryant, T
Zhang, YT
Brewer, M
Duff, A
Biddick, L
Singh, A
Lightfoot, S
Steele, VE
Rao, CV
AF Janakiram, Naveena B.
Mohammed, Altaf
Bryant, Taylor
Zhang, Yuting
Brewer, Misty
Duff, Ashley
Biddick, Laura
Singh, Anil
Lightfoot, Stan
Steele, Vernon E.
Rao, Chinthalapally V.
TI Potentiating NK cell activity by combination of Rosuvastatin and
Difluoromethylornithine for effective chemopreventive efficacy against
Colon Cancer
SO SCIENTIFIC REPORTS
LA English
DT Article
ID ORNITHINE-DECARBOXYLASE; COLORECTAL-CANCER;
ALPHA-DIFLUOROMETHYLORNITHINE; DOUBLE-BLIND; STATINS; MICE;
CARCINOGENESIS; PREVENTION; INHIBITOR; ADENOMAS
AB Colorectal cancer (CRC) is the second highest cause of cancer-related deaths. A successful strategy to improve chemopreventive efficacies is by down-regulating tumor polyamines and enhancing NK cell activities. Colonic carcinogenesis was induced by azoxymethane (AOM) in male F344 rats. Eight weeks after AOM treatment, animals were fed diets containing Rosuvastatin and difluromethylornithine (DFMO) individually and in combination for 40 weeks. Both agents showed significant suppression of adenocarcinoma multiplicity and incidence with no toxicity compared to untreated rats. Low-dose Rosuvastatin plus DFMO suppressed colon adenocarcinoma multiplicity by 76% compared to low-dose Rosuvastatin (29%) and DFMO (46%), suggesting additive efficacy. Furthermore, low-dose combination caused a delay in colonic adenocarcinoma progression. DFMO, Rosuvastatin and/or combinations significantly decreased polyamine content and increased intra-tumoral NK cells expressing perforin plus IFN-gamma compared to untreated colon tumors. Further ex-vivo analysis of splenic NK cells exposed to DFMO, Rosuvastatin or combination resulted in an increase of NKs with perforin expression. This is the first report on Rosuvastatin alone or combination strategy using clinically relevant statin plus DFMO doses which shows a significant suppression of colon adenocarcinomas, and their potential in increasing functional NK cells. This strategy has potential for further testing in high risk individuals for colon cancer.
C1 [Janakiram, Naveena B.; Mohammed, Altaf; Bryant, Taylor; Zhang, Yuting; Brewer, Misty; Duff, Ashley; Biddick, Laura; Singh, Anil; Lightfoot, Stan; Rao, Chinthalapally V.] Univ Oklahoma, Hlth Sci Ctr, Ctr Canc Prevent & Drug Dev, Dept Med,Hematol Oncol Sect,Stephenson Canc Ctr, Oklahoma City, OK 73104 USA.
[Steele, Vernon E.] NCI, Chemoprevent Agent Dev Res Grp, Canc Prevent Div, Bethesda, MD 20892 USA.
RP Janakiram, NB; Rao, CV (reprint author), Univ Oklahoma, Hlth Sci Ctr, Ctr Canc Prevent & Drug Dev, Dept Med,Hematol Oncol Sect,Stephenson Canc Ctr, Oklahoma City, OK 73104 USA.
EM njanakir@ouhsc.edu; cv-rao@ouhsc.edu
FU [NCI R01-CA-094962]; [NCI-CN-N01-53300]
FX The authors thank Ms. Agata Bien and Ms. Kathy Kyler, Staff Editor, for
editorial assistance with this article. The authors also thank Jim
Henthorn at the Flow Cytometry Core for his assistance with flow work
and the OUHSC Rodent Barrier Facility staff for the valuable support in
bioassay studies. This study was supported by grants NCI R01-CA-094962 &
NCI-CN-N01-53300.
NR 48
TC 0
Z9 0
U1 2
U2 2
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2045-2322
J9 SCI REP-UK
JI Sci Rep
PD NOV 14
PY 2016
VL 6
AR 37046
DI 10.1038/srep37046
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EB7AE
UT WOS:000387536300001
PM 27841323
ER
PT J
AU Lipsitch, M
Barclay, W
Raman, R
Russell, CJ
Belser, JA
Cobey, S
Kasson, PM
Lloyd-Smith, JO
Maurer-Stroh, S
Riley, S
Beauchemin, CAA
Bedford, T
Friedrich, TC
Handel, A
Herfst, S
Murcia, PR
Roche, B
Wilke, CO
Russell, CA
AF Lipsitch, Marc
Barclay, Wendy
Raman, Rahul
Russell, Charles J.
Belser, Jessica A.
Cobey, Sarah
Kasson, Peter M.
Lloyd-Smith, James O.
Maurer-Stroh, Sebastian
Riley, Steven
Beauchemin, Catherine A. A.
Bedford, Trevor
Friedrich, Thomas C.
Handel, Andreas
Herfst, Sander
Murcia, Pablo R.
Roche, Benjamin
Wilke, Claus O.
Russell, Colin A.
TI Viral factors in influenza pandemic risk assessment
SO ELIFE
LA English
DT Article
ID RECEPTOR-BINDING PROPERTIES; UPPER RESPIRATORY-TRACT; SINGLE AMINO-ACID;
A H7N9 VIRUS; MEMBRANE-FUSION; HEMAGGLUTININ PROTEIN; HONG-KONG; POULTRY
WORKERS; HUMAN INFECTION; A(H7N9) VIRUS
AB The threat of an influenza A virus pandemic stems from continual virus spillovers from reservoir species, a tiny fraction of which spark sustained transmission in humans. To date, no pandemic emergence of a new influenza strain has been preceded by detection of a closely related precursor in an animal or human. Nonetheless, influenza surveillance efforts are expanding, prompting a need for tools to assess the pandemic risk posed by a detected virus. The goal would be to use genetic sequence and/or biological assays of viral traits to identify those non-human influenza viruses with the greatest risk of evolving into pandemic threats, and/or to understand drivers of such evolution, to prioritize pandemic prevention or response measures. We describe such efforts, identify progress and ongoing challenges, and discuss three specific traits of influenza viruses (hemagglutinin receptor binding specificity, hemagglutinin pH of activation, and polymerase complex efficiency) that contribute to pandemic risk.
C1 [Lipsitch, Marc] Harvard TH Chan Sch Pub Hlth, Ctr Communicable Dis Dynam, Boston, MA 02115 USA.
[Lipsitch, Marc] Harvard TH Chan Sch Pub Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Lipsitch, Marc] Harvard TH Chan Sch Pub Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA.
[Barclay, Wendy] Imperial Coll, Fac Med, Div Infect Dis, London, England.
[Raman, Rahul] MIT, Dept Biol Engn, Koch Inst Intergrat Canc Res, Cambridge, MA 02139 USA.
[Russell, Charles J.] St Jude Childrens Res Hosp, Dept Infect Dis, 332 N Lauderdale St, Memphis, TN 38105 USA.
[Belser, Jessica A.] Ctr Dis Control & Prevent, Atlanta, GA USA.
[Cobey, Sarah] Univ Chicago, Dept Ecol & Evolut Biol, Chicago, IL 60637 USA.
[Kasson, Peter M.] Univ Virginia, Dept Biomed Engn, Charlottesville, VA USA.
[Kasson, Peter M.] Univ Virginia, Dept Mol Physiol & Biol Phys, Charlottesville, VA USA.
[Lloyd-Smith, James O.] Univ Calif Los Angeles, Dept Ecol & Evolutionary Biol, Los Angeles, CA USA.
[Lloyd-Smith, James O.] NIH, Fogarty Int Ctr, Bldg 10, Bethesda, MD 20892 USA.
[Maurer-Stroh, Sebastian] Agcy Sci Technol & Res, Bioinformat Inst, Singapore, Singapore.
[Maurer-Stroh, Sebastian] Minist Hlth, Communicable Dis Div, Natl Publ Hlth Lab, Singapore, Singapore.
[Maurer-Stroh, Sebastian] Nanyang Technol Univ, Sch Biol Sci, Singapore, Singapore.
[Riley, Steven] Imperial Coll London, Sch Publ Hlth, MRC Ctr Outbreak Anal & Modelling, London, England.
[Riley, Steven] Imperial Coll London, Sch Publ Hlth, Dept Infect Dis Epidemiol, London, England.
[Beauchemin, Catherine A. A.] Ryerson Univ, Dept Phys, Toronto, ON, Canada.
[Bedford, Trevor] Fred Hutchinson Canc Res Ctr, Vaccine & Infect Dis Div, 1124 Columbia St, Seattle, WA 98104 USA.
[Friedrich, Thomas C.] Univ Wisconsin, Sch Vet Med, Dept Pathobiol Sci, Madison, WI 53706 USA.
[Handel, Andreas] Univ Georgia, Coll Publ Hlth, Dept Edidemiol & Biostat, Athens, GA 30602 USA.
[Herfst, Sander] Erasmus MC, Dept Virosci, Rotterdam, Netherlands.
[Murcia, Pablo R.] MRC Univ Glasgow, Ctr Virus Res, Glasgow, Lanark, Scotland.
[Roche, Benjamin] IRD UPMC UMMISCO, Montpellier, France.
[Wilke, Claus O.] Univ Texas Austin, Inst Cellular & Mol Biol, Ctr Computat Biol & Bioinformat, Austin, TX 78712 USA.
[Wilke, Claus O.] Univ Texas Austin, Dept Integrat Biol, Austin, TX 78712 USA.
[Russell, Colin A.] Univ Cambridge, Dept Vet Med, Cambridge, England.
RP Lipsitch, M (reprint author), Harvard TH Chan Sch Pub Hlth, Ctr Communicable Dis Dynam, Boston, MA 02115 USA.; Lipsitch, M (reprint author), Harvard TH Chan Sch Pub Hlth, Dept Epidemiol, Boston, MA 02115 USA.; Lipsitch, M (reprint author), Harvard TH Chan Sch Pub Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA.
EM mlipsitc@hsph.harvard.edu
OI Lipsitch, Marc/0000-0003-1504-9213
FU National Institutes of Health [U54 GM088558, R01 GM098304, R01
GM088344]; National Institute of Allergy and Infectious Diseases Centers
of Excellence for Influenza Research and Surveillance
[HHSN272201400006C]; National Health and Medical Research Council
[12/1/06/24/5793]; Agency for Science, Technology and Research
[12/1/06/24/5793]; Wellcome [093488/Z/10/Z, 200187/Z/15/Z,
200861/Z/16/Z]; Medical Research Council [MR/J008761/1, G0801822];
National Institute of General Medical Sciences [MIDAS U01 GM110721-01];
Natural Sciences and Engineering Research Council of Canada
[355837-2013]; Ministry of Research and Innovation of Ontario
[ER13-09-040]; Nederlandse Organisatie voor Wetenschappelijk Onderzoek
VIDI grant [91715372]; Royal Society University
FX National Institutes of Health U54 GM088558 Marc Lipsitch; National
Institutes of Health RAPIDD program, Science and Technology Directorate,
U.S Department of Homeland Security, and the Fogarty International
Center Marc Lipsitch; National Institute of Allergy and Infectious
Diseases Centers of Excellence for Influenza Research and Surveillance
(Contract HHSN272201400006C) Charles J Russel; National Institutes of
Health R01 GM098304 Peter M Kasson; National Health and Medical Research
Council 12/1/06/24/5793 Sebastian Maurer-Stroh; Agency for Science,
Technology and Research 12/1/06/24/5793 Sebastian Maurer-Stroh; Wellcome
Project 093488/Z/10/Z Steven Riley; Wellcome 200187/Z/15/Z Steven Riley;
Wellcome 200861/Z/16/Z Steven Riley; Medical Research Council
MR/J008761/1 Steven Riley; National Institute of General Medical
Sciences MIDAS U01 GM110721-01 Steven Riley; Natural Sciences and
Engineering Research Council of Canada 355837-2013 Catherine AA
Beauchemin; Ministry of Research and Innovation of Ontario ER13-09-040
Catherine AA Beauchemin; Nederlandse Organisatie voor Wetenschappelijk
Onderzoek VIDI grant 91715372 Sander Herfst; Medical Research Council
G0801822 Pablo R Murcia; National Institutes of Health R01 GM088344
Claus O Wilke; Royal Society University Research Fellowship Colin A
Russell; The funders had no role in study design, data collection and
interpretation, or the decision to submit the work for publication.
NR 240
TC 2
Z9 2
U1 5
U2 5
PU ELIFE SCIENCES PUBLICATIONS LTD
PI CAMBRIDGE
PA SHERATON HOUSE, CASTLE PARK, CAMBRIDGE, CB3 0AX, ENGLAND
SN 2050-084X
J9 ELIFE
JI eLife
PD NOV 11
PY 2016
VL 5
AR e18491
DI 10.7554/eLife.18491
PG 38
WC Biology
SC Life Sciences & Biomedicine - Other Topics
GA EG8AB
UT WOS:000391276700001
ER
PT J
AU Rebbeck, TR
Friebel, TM
Mitra, N
Wan, F
Chen, S
Andrulis, IL
Apostolou, P
Arnold, N
Arun, BK
Barrowdale, D
Benitez, J
Berger, R
Berthet, P
Borg, A
Buys, SS
Caldes, T
Carter, J
Chiquette, J
Claes, KBM
Couch, FJ
Cybulski, C
Daly, MB
de la Hoya, M
Diez, O
Domchek, SM
Nathanson, KL
Durda, K
Ellis, S
Evans, DG
Foretova, L
Friedman, E
Frost, D
Ganz, PA
Garber, J
Glendon, G
Godwin, AK
Greene, MH
Gronwald, J
Hahnen, E
Hallberg, E
Hamann, U
Hansen, TVO
Imyanitov, EN
Isaacs, C
Jakubowska, A
Janavicius, R
Jaworska-Bieniek, K
John, EM
Karlan, BY
Kaufman, B
Kwong, A
Laitman, Y
Lasset, C
Lazaro, C
Lester, J
Loman, N
Lubinski, J
Manoukian, S
Mitchell, G
Montagna, M
Neuhausen, SL
Nevanlinna, H
Niederacher, D
Nussbaum, RL
Offit, K
Olah, E
Olopade, OI
Park, SK
Piedmonte, M
Radice, P
Rappaport-Fuerhauser, C
Rookus, MA
Seynaeve, C
Simard, J
Singer, CF
Soucy, P
Southey, M
Stoppa-Lyonnet, D
Sukiennicki, G
Szabo, CI
Tancredi, M
Teixeira, MR
Teo, SH
Terry, MB
Thomassen, M
Tihomirova, L
Tischkowitz, M
Toland, AE
Toloczko-Grabarek, A
Tung, N
van Rensburg, EJ
Villano, D
Wang-Gohrke, S
Wappenschmidt, B
Weitzel, JN
Zidan, J
Zorn, KK
McGuffog, L
Easton, D
Chenevix-Trench, G
Antoniou, AC
Ramus, SJ
AF Rebbeck, Timothy R.
Friebel, Tara M.
Mitra, Nandita
Wan, Fei
Chen, Stephanie
Andrulis, Irene L.
Apostolou, Paraskevi
Arnold, Norbert
Arun, Banu K.
Barrowdale, Daniel
Benitez, Javier
Berger, Raanan
Berthet, Pascaline
Borg, Ake
Buys, Saundra S.
Caldes, Trinidad
Carter, Jonathan
Chiquette, Jocelyne
Claes, Kathleen B. M.
Couch, Fergus J.
Cybulski, Cezary
Daly, Mary B.
de la Hoya, Miguel
Diez, Orland
Domchek, Susan M.
Nathanson, Katherine L.
Durda, Katarzyna
Ellis, Steve
Evans, D. Gareth
Foretova, Lenka
Friedman, Eitan
Frost, Debra
Ganz, Patricia A.
Garber, Judy
Glendon, Gord
Godwin, Andrew K.
Greene, Mark H.
Gronwald, Jacek
Hahnen, Eric
Hallberg, Emily
Hamann, Ute
Hansen, Thomas V. O.
Imyanitov, Evgeny N.
Isaacs, Claudine
Jakubowska, Anna
Janavicius, Ramunas
Jaworska-Bieniek, Katarzyna
John, Esther M.
Karlan, Beth Y.
Kaufman, Bella
Kwong, Ava
Laitman, Yael
Lasset, Christine
Lazaro, Conxi
Lester, Jenny
Loman, Niklas
Lubinski, Jan
Manoukian, Siranoush
Mitchell, Gillian
Montagna, Marco
Neuhausen, Susan L.
Nevanlinna, Heli
Niederacher, Dieter
Nussbaum, Robert L.
Offit, Kenneth
Olah, Edith
Olopade, Olufunmilayo I.
Park, Sue Kyung
Piedmonte, Marion
Radice, Paolo
Rappaport-Fuerhauser, Christine
Rookus, Matti A.
Seynaeve, Caroline
Simard, Jacques
Singer, Christian F.
Soucy, Penny
Southey, Melissa
Stoppa-Lyonnet, Dominique
Sukiennicki, Grzegorz
Szabo, Csilla I.
Tancredi, Mariella
Teixeira, Manuel R.
Teo, Soo-Hwang
Terry, Mary Beth
Thomassen, Mads
Tihomirova, Laima
Tischkowitz, Marc
Toland, Amanda Ewart
Toloczko-Grabarek, Aleksandra
Tung, Nadine
van Rensburg, Elizabeth J.
Villano, Danylo
Wang-Gohrke, Shan
Wappenschmidt, Barbara
Weitzel, Jeffrey N.
Zidan, Jamal
Zorn, Kristin K.
McGuffog, Lesley
Easton, Douglas
Chenevix-Trench, Georgia
Antoniou, Antonis C.
Ramus, Susan J.
CA EMBRACE
HEBON
KConFab Investigators
TI Inheritance of deleterious mutations at both BRCA1 and BRCA2 in an
international sample of 32,295 women
SO BREAST CANCER RESEARCH
LA English
DT Article
DE Hereditary breast and ovarian cancer; Transheterozygosity; BRCA1; BRCA2
ID UNKNOWN CLINICAL-SIGNIFICANCE; CANCER SUSCEPTIBILITY GENE; SPORADIC
BREAST-CANCER; DNA-SEQUENCE VARIANTS; WILD-TYPE CHROMOSOME;
OVARIAN-CANCER; FANCONI-ANEMIA; DOUBLE HETEROZYGOSITY; GERMLINE
MUTATIONS; HETEROGENIC LOSS
AB Background: Most BRCA1 or BRCA2 mutation carriers have inherited a single (heterozygous) mutation. Transheterozygotes (TH) who have inherited deleterious mutations in both BRCA1 and BRCA2 are rare, and the consequences of transheterozygosity are poorly understood.
Methods: From 32,295 female BRCA1/2 mutation carriers, we identified 93 TH (0.3 %). "Cases" were defined as TH, and "controls" were single mutations at BRCA1 (SH1) or BRCA2 (SH2). Matched SH1 "controls" carried a BRCA1 mutation found in the TH "case". Matched SH2 "controls" carried a BRCA2 mutation found in the TH "case". After matching the TH carriers with SH1 or SH2, 91 TH were matched to 9316 SH1, and 89 TH were matched to 3370 SH2.
Results: The majority of TH (45.2 %) involved the three common Jewish mutations. TH were more likely than SH1 and SH2 women to have been ever diagnosed with breast cancer (BC; p = 0.002). TH were more likely to be diagnosed with ovarian cancer (OC) than SH2 (p = 0.017), but not SH1. Age at BC diagnosis was the same in TH vs. SH1 (p = 0.231), but was on average 4.5 years younger in TH than in SH2 (p < 0.001). BC in TH was more likely to be estrogen receptor (ER) positive (p = 0.010) or progesterone receptor (PR) positive (p = 0.013) than in SH1, but less likely to be ER positive (p < 0.001) or PR positive (p = 0.012) than SH2. Among 15 tumors from TH patients, there was no clear pattern of loss of heterozygosity (LOH) for BRCA1 or BRCA2 in either BC or OC.
Conclusions: Our observations suggest that clinical TH phenotypes resemble SH1. However, TH breast tumor marker characteristics are phenotypically intermediate to SH1 and SH2.
C1 [Rebbeck, Timothy R.; Friebel, Tara M.; Garber, Judy] Dana Farber Canc Inst, Dept Epidemiol, 1101 Dana Bldg,450 Brookline Ave, Boston, MA 02115 USA.
[Rebbeck, Timothy R.; Friebel, Tara M.; Garber, Judy] Harvard TH Chan Sch Publ Hlth, 1101 Dana Bldg,450 Brookline Ave, Boston, MA USA.
[Mitra, Nandita] Univ Penn, Perelman Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA.
[Wan, Fei] Grp Hlth, Biostat Unit, Res Inst, Seattle, WA USA.
[Chen, Stephanie; Ramus, Susan J.] Univ So Calif, Keck Sch Med, USC Norris Comprehens Canc Ctr, Dept Prevent Med, Los Angeles, CA 90033 USA.
[Barrowdale, Daniel; Chenevix-Trench, Georgia] QIMR Berghofer Inst Med Res, Dept Genet & Computat Biol, Brisbane, Qld, Australia.
[McGuffog, Lesley; Easton, Douglas; Antoniou, Antonis C.] Univ Cambridge, Dept Publ Hlth & Primary Care, Ctr Canc Genet Epidemiol, Cambridge, England.
[Andrulis, Irene L.] Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, Toronto, ON M5G 1X5, Canada.
[Andrulis, Irene L.] Univ Toronto, Dept Mol Genet & Lab Med, Toronto, ON, Canada.
[Andrulis, Irene L.] Univ Toronto, Dept Pathobiol, Toronto, ON, Canada.
[Apostolou, Paraskevi] Natl Ctr Sci Res Demokritos, INRASTES Inst Nucl & Radiol Sci & Technol, Mol Diagnost Lab, Patriarchou Gregoriou & Neapoleos Str Aghia Paras, Athens, Greece.
[Arnold, Norbert] Univ Kiel, Univ Hosp Schleswig Holstein, Dept Obstet & Gynaecol, Campus Kiel, Kiel, Germany.
[Arun, Banu K.] Univ Texas MD Anderson Canc Ctr, Dept Breast Med Oncol, 1515 Pressler St,CBP 5, Houston, TX USA.
[Arun, Banu K.] Univ Texas MD Anderson Canc Ctr, Clin Canc Genet Program, 1515 Pressler St,CBP 5, Houston, TX USA.
[Benitez, Javier] Spanish Natl Canc Ctr CNIO, Human Genet Grp, Madrid, Spain.
[Benitez, Javier] Biomed Network Rare Dis CIBERER, Madrid, Spain.
[Benitez, Javier] Spanish Natl Canc Res Ctr CNIO, Human Canc Genet Program, Human Genotyping CEGEN Unit, Madrid, Spain.
[Berger, Raanan; Kaufman, Bella] Chaim Sheba Med Ctr, Inst Oncol, IL-52621 Ramat Gan 52621, Israel.
[Berthet, Pascaline] Ctr Francois Baclesse, 3 Ave General Harris, Caen, France.
[Borg, Ake] Lund Univ, Dept Oncol Clin Sci, Lund, Sweden.
[Borg, Ake] Skane Univ Hosp, Lund, Sweden.
[Buys, Saundra S.] Huntsman Canc Inst, Dept Med, 2000 Circle Hope, Salt Lake City, UT 84112 USA.
[Caldes, Trinidad; de la Hoya, Miguel] Hosp Clin San Carlos, IdISSC El Inst Invest Sanit Hosp Clin San Carlos, Mol Oncol Lab, Martin Lagos S N, Madrid, Spain.
[Carter, Jonathan] Univ Sydney, Ctr Canc, Royal Prince Alfred Hosp, Gynaecol Oncol, Sydney, NSW, Australia.
[Chiquette, Jocelyne] Hop St Sacrement, Ctr Malad Sein Deschenes Fabia, Unite Rech SantePopulat, 1050 Chemin Sainte Foy, Quebec City, PQ, Canada.
[Claes, Kathleen B. M.] Univ Ghent, Ctr Med Genet, Pintelaan 185, B-9000 Ghent, Belgium.
[Couch, Fergus J.] Mayo Clin, Dept Lab Med & Pathol, 200 First St SW, Rochester, MN USA.
[Cybulski, Cezary; Durda, Katarzyna; Gronwald, Jacek; Jakubowska, Anna; Jaworska-Bieniek, Katarzyna; Lubinski, Jan; Sukiennicki, Grzegorz; Toloczko-Grabarek, Aleksandra] Pomeranian Med Univ, Dept Genet & Pathol, Polabska 4, Szczecin, Poland.
[Daly, Mary B.] Fox Chase Canc Ctr, Div Populat Sci, 333 Cottman Ave, Philadelphia, PA 19111 USA.
[Diez, Orland] Vall dHebron Univ Hosp, Vall dHebron Inst Oncol VHIO, Oncogenet Grp, Clinical & Mol Genet Area, Barcelona 11929, Spain.
[Domchek, Susan M.; Nathanson, Katherine L.] Univ Penn, Perelman Sch Med, Abramson Canc Ctr, Dept Med, Philadelphia, PA USA.
[Ellis, Steve; Frost, Debra; EMBRACE] Univ Cambridge, Dept Publ Hlth & Primary Care, Strangeways Res Lab, Ctr Canc Genet Epidemiol, Worts Causeway, Cambridge, England.
[Evans, D. Gareth] Cent Manchester Univ Hosp NHS Fdn Trust, Manchester Acad Hlth Sci Ctr, Inst Human Dev, Genom Med, Manchester, Lancs, England.
[Foretova, Lenka] Masaryk Mem Canc Inst, Dept Canc Epidemiol & Genet, Zluty Kopec 7, Brno 65653, Czech Republic.
[Friedman, Eitan; Laitman, Yael] Chaim Sheba Med Ctr, Inst Human Genet, Susanne Levy Gertner Oncogenet Unit, IL-52621 Ramat Gan, Israel.
[Friedman, Eitan; Laitman, Yael] Tel Aviv Univ, Sackler Fac Med, IL-69978 Ramat Aviv, Israel.
[Ganz, Patricia A.] Univ Calif Los Angeles, Johnsson Comprehens Canc Ctr, Div Canc Prevent & Control Res, Sch Med, 650 Charles Young Dr South,Room A2-125 HS, Los Angeles, CA 90095 USA.
[Ganz, Patricia A.] Univ Calif Los Angeles, Johnsson Comprehens Canc Ctr, Div Canc Prevent & Control Res, Sch Publ Hlth, 650 Charles Young Dr South,Room A2-125 HS, Los Angeles, CA 90095 USA.
[Glendon, Gord] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Ontario Canc Genet Network, Toronto, ON M5G 1X5, Canada.
[Godwin, Andrew K.] Dept Pathol & Lab Med, 3901 Rainbow Blvd,4019 Wahl Hall EastMS 3040, Kansas City, KS USA.
[Godwin, Andrew K.] Univ Kansas, Med Ctr, Kansas City, KS 66103 USA.
[Greene, Mark H.] NIH, NCI, DCEG, Clin Genet Branch, 9609 Med Ctr Dr,Room 6E-454, Bethesda, MD USA.
[Hahnen, Eric; Wappenschmidt, Barbara] Univ Cologne, Ctr Hereditary Breast & Ovarian Canc CIO, Cologne, Germany.
[Hahnen, Eric; Wappenschmidt, Barbara] Univ Cologne, Fac Med, Ctr Mol Med Cologne CMMC, Cologne, Germany.
[Hahnen, Eric; Wappenschmidt, Barbara] Univ Hosp Cologne, Cologne, Germany.
[Hallberg, Emily] Mayo Clin, Dept Hlth Sci Res, 13400 E Scottsdale Blvd, Scottsdale, AZ USA.
[Hamann, Ute] German Canc Res Ctr, Mol Genet Breast Canc, Neuenheimer Feld 580, D-69120 Heidelberg, Germany.
[Hansen, Thomas V. O.] Univ Copenhagen Hosp, Rigshosp, Ctr Genom Med, Blegdamsvej 9, DK-2100 Copenhagen, Denmark.
Hereditary Breast & Ovarian Canc Res Grp Netherla, Amsterdam, Netherlands.
[HEBON] Netherlands Canc Inst, Amsterdam, Netherlands.
[Imyanitov, Evgeny N.] NN Petrov Inst Oncol, St Petersburg 197758, Russia.
[Isaacs, Claudine] Georgetown Univ, Lombardi Comprehens Canc Ctr, 3800 Reservoir Rd NW, Washington, DC USA.
[Janavicius, Ramunas] Vilnius Univ Hosp Santariskiu Clin, Hematol Oncol & Transfus Med Ctr, Dept Mol & Regenerat Med, Santariskiu St, Vilnius, Lithuania.
[Janavicius, Ramunas] State Res Inst Ctr Innovat Med, Zygymantu St 9, Vilnius, Lithuania.
[John, Esther M.] Canc Prevent Inst Calif, Dept Epidemiol, 2201 Walnut Ave,Suite 300, Fremont, CA 94538 USA.
[Karlan, Beth Y.; Lester, Jenny] Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Inst, Womens Canc Program, 8700 Beverly Blvd,Suite 290W, Los Angeles, CA USA.
[KConFab Investigators] Peter MacCallum Canc Ctr, Kathleen Cuningham Consortium Res Familial Breast, Melbourne, Vic, Australia.
[Kwong, Ava] Hong Kong Hereditary Breast Canc Family Registry, Hong Kong, Hong Kong, Peoples R China.
[Kwong, Ava] Hong Kong Sanat & Hosp, Canc Genet Ctr, Hong Kong, Hong Kong, Peoples R China.
[Kwong, Ava] Univ Hong Kong, Dept Surg, Hong Kong, Hong Kong, Peoples R China.
[Lasset, Christine] Ctr Leon Berard, Unite Prevent & Epidemiol Genet, 28 Rue Laennec, Lyon, France.
[Lazaro, Conxi] IDIBELL Bellvitge Biomed Res Inst, Hereditary Canc Program, Catalan Inst Oncol, Mol Diagnost Unit,LHosp Barcelona, Gran Via Hosp 199-203, Barcelona 08908, Spain.
[Loman, Niklas] Univ Lund Hosp, Dept Oncol, Lund, Sweden.
[Manoukian, Siranoush] Fdn IRCCS, Dept Prevent & Predict Med, Ist Nazl Tumori, Unit Med Genet, Via Giacomo Venezian 1, I-20133 Milan, Italy.
[Mitchell, Gillian] Peter MacCallum Canc Ctr, Familial Canc Ctr, Locked Bag 1,ABeckett St, Melbourne, Vic 8006, Australia.
[Mitchell, Gillian] Univ Melbourne, Sir Peter MacCallum Dept Oncol, Parkville, Vic 3052, Australia.
[Montagna, Marco] IRCCS, Veneto Inst Oncol IOC, Immunol & Mol Oncol Unit, Via Gattamelata 64, Padua, Italy.
[Neuhausen, Susan L.] Beckman Res Inst City Hope, Dept Populat Sci, Duarte, CA USA.
[Nevanlinna, Heli] Univ Helsinki, Dept Obstet & Gynecol, POB 700,Haartmaninkatu 8, Helsinki 00029, Finland.
[Nevanlinna, Heli] HUS, Helsinki Univ Hosp, Biomed Helsinki, POB 700,Haartmaninkatu 8, Helsinki 00029, Finland.
[Niederacher, Dieter] Univ Dusseldorf, Univ Hosp Dusseldorf, Dept Obstet & Gynaecol, Dusseldorf, Germany.
[Nussbaum, Robert L.] 62513 Parnassus Ave,HSE 901E, San Francisco, CA 94143 USA.
[Offit, Kenneth] Mem Sloan Kettering Canc Ctr, Dept Med Canc Biol & Genet, Clin Genet Res Lab, 1275 York Ave, New York, NY 10044 USA.
[Olah, Edith] Natl Inst Oncol, Dept Mol Genet, Budapest, Hungary.
[Olopade, Olufunmilayo I.] 5841 South Maryland Ave, Chicago, IL USA.
[Park, Sue Kyung] Seoul Natl Univ, Coll Med, Dept Prevent Med, 103 Daehak Ro, Seoul 110799, South Korea.
[Piedmonte, Marion] Roswell Pk Canc Inst, NRG Oncol Stat & Data Management Ctr, Elm St & Carlton St, Buffalo, NY 14263 USA.
[Radice, Paolo] Fdn IRCCS, Dept Prevent & Predicted Med, Ist Nazl Tumori, Unit Mol Bases Genet Risk & Genet Testing, Amaedeolab Via GA Amadeo 42, I-20133 Milan, Italy.
[Rappaport-Fuerhauser, Christine] Med Univ Vienna, Dept OB GYN, Waehringer Guertel 18-20, A-1090 Vienna, Austria.
[Rookus, Matti A.] Netherlands Canc Inst, Dept Epidemiol, POB 902031000, Amsterdam, Netherlands.
[Seynaeve, Caroline] Erasmus MC, Inst Canc, Family Canc Clin, Dept Med Oncol, POB 52013008, Rotterdam, Netherlands.
[Simard, Jacques; Soucy, Penny] Univ Quebec, Res Ctr, Ctr Hosp, Genom Ctr, 2705 Laurier Blvd, Quebec City, PQ, Canada.
[Simard, Jacques; Soucy, Penny] Univ Laval, 2705 Laurier Blvd, Quebec City, PQ, Canada.
[Singer, Christian F.] Med Univ Vienna, Dept OB GYN, Waehringer Guertel 18-20, A-1090 Vienna, Austria.
[Singer, Christian F.] Med Univ Vienna, Ctr Comprehens Canc, Waehringer Guertel 18-20, A-1090 Vienna, Austria.
[Southey, Melissa] Univ Melbourne, Dept Pathol, Genet Epidemiol Lab, Parkville, Vic, Australia.
[Stoppa-Lyonnet, Dominique] Inst Curie, Serv Genet Oncol, 26 Rue dUlm, Paris 05, France.
[Szabo, Csilla I.] Natl Inst Hlth, NHGRI, Bldg 50,Room 5312,50 South Dr,MSC 004, Bethesda, MD 20892 USA.
[Tancredi, Mariella] Univ Pisa, Dept Lab Med, Sect Genet Oncol, Pisa, Italy.
[Tancredi, Mariella] Univ Hosp Pisa, Pisa, Italy.
[Teixeira, Manuel R.] Portuguese Oncol Inst, Dept Genet, Rua Dr Antonio Bernardino Almeida, P-4200072 Oporto, Portugal.
[Teo, Soo-Hwang] Sime Darby Med Ctr, Canc Res Initiat Fdn, 1 Jalan SS12-1A, Subang Jaya 47500, Malaysia.
[Teo, Soo-Hwang] Univ Malaya, Canc Res Inst, Kuala Lumpur 50603, Malaysia.
[Terry, Mary Beth] Columbia Univ, Dept Epidemiol, New York, NY USA.
[Thomassen, Mads] Odense Univ Hosp, Dept Clin Genet, Sonder Blvd 29, Odense C, Denmark.
[Tihomirova, Laima] Latvian Biomed Res & Study Ctr, Ratsupites Str 1, Riga, Latvia.
[Tischkowitz, Marc] McGill Univ, Dept Human Genet & Oncol, Program Canc Genet, Montreal, PQ, Canada.
[Toland, Amanda Ewart] Ohio State Univ, Ctr Comprehens Canc, Dept Internal Med & Mol Virol, Div Human Canc Genet, 998 Biomed Res Tower, Columbus, OH USA.
[Toland, Amanda Ewart] Ohio State Univ, Ctr Comprehens Canc, Dept Immunol & Med Genet, Div Human Canc Genet, 998 Biomed Res Tower, Columbus, OH USA.
[Tung, Nadine] Beth Israel Deaconess Med Ctr, Dept Med Oncol, 330 Brookline Ave, Boston, MA 02215 USA.
[van Rensburg, Elizabeth J.] Univ Pretoria, Dept Genet, Canc Genet Lab, Private Bag X323, ZA-0007 Arcadia, South Africa.
[Villano, Danylo] Mem Sloan Kettering Canc Ctr, Clin Canc Genet Lab, New York, NY USA.
[Wang-Gohrke, Shan] Univ Hosp Ulm, Dept Obstet & Gynaecol, Ulm, Germany.
[Weitzel, Jeffrey N.] City Hope Natl Med Ctr, Clin Canc Genet, 1500 East Duarte Rd, Duarte, CA 91010 USA.
[Zidan, Jamal] Inst Oncol, Rivka Ziv Med Ctr, IL-13000 Safed, Israel.
[Zidan, Jamal] Bar Ilan Univ, Fac Med, Safed, Israel.
[Zorn, Kristin K.] 934301 West Markham St,Slot 793, Little Rock, AR 72205 USA.
[Ramus, Susan J.] Univ New South Wales, Sch Womens & Childrens Hlth, 384 Victoria St, Darlinghurst, NSW 2010, Australia.
[Ramus, Susan J.] Garvan Inst Med Res, Kinghorn Canc Ctr, 384 Victoria St, Darlinghurst, NSW 2010, Australia.
RP Rebbeck, TR (reprint author), Dana Farber Canc Inst, Dept Epidemiol, 1101 Dana Bldg,450 Brookline Ave, Boston, MA 02115 USA.; Rebbeck, TR (reprint author), Harvard TH Chan Sch Publ Hlth, 1101 Dana Bldg,450 Brookline Ave, Boston, MA USA.
EM Timothy_Rebbeck@dfci.harvard.edu
RI Gronwald, Jacek/A-4576-2017; Jansen van Rensburg, Elizabeth
(Lizette)/B-9104-2011; Arnold, Norbert/E-3012-2010; manoukian,
siranoush/E-7132-2017; montagna, marco/E-2225-2012
OI Gronwald, Jacek/0000-0002-3643-2871; Arnold,
Norbert/0000-0003-4523-8808; manoukian, siranoush/0000-0002-6034-7562;
montagna, marco/0000-0002-4929-2150
FU National Cancer Institute [UM1 CA164920, RC4CA153828]; Lithuania
(BFBOCC-LT): Research Council of Lithuania grant [SEN-18/2015]; Breast
Cancer Research Foundation; Cancer Association of South Africa (CANSA);
Morris and Horowitz Families Endowed Professorship; Spanish Association
against Cancer [AECC08, RTICC 06/0020/1060, FISPI08/1120]; Mutua
Madrilena Foundation (FMMA); Office of the Director, National Institutes
of Health; Italian citizens of the Fondazione IRCCS Istituto Nazionale
Tumori; Cancer Research UK [C12292/A20861,
C1287/A11990C5047/A8385C1287/A10118 C1287/A 10710
C12292/A11174 C1281/A12014 C5047/A8384 C5047/A15007
C5047/A10692 C8197/A16565]; European Union (European Social Fund -
ESF); Greek national funds through the Operational Program "Education
and Lifelong Learning" of the National Strategic Reference Framework
(NSRF) - Research Funding Program of the General Secretariat for
Research Technology [SYN11_10_19 NBCA]; DKFZ; NIHR; University of Kansas
Cancer Center [P30 CA168524]; Kansas Bioscience Authority Eminent
Scholar Program; Chancellors Distinguished Chair in Biomedical Sciences
Professorship; German Cancer Aid [110837]; Center for Molecular Medicine
Cologne (CMMC); Ligue Nationale Contre le Cancer; Association "Le cancer
du sein, parlons-en!" Award; Canadian Institutes of Health Research;
French National Institute of Cancer (INCa); Non-Therapeutic Subject
Registry Shared Resource at Georgetown University (NIH/NCI grant)
[P30-CA051008]; Fisher Center for Familial Cancer Research; Swing Fore
the Cure; ISCIII (Spain) [RD12/0036/0006, 15/00059]; European Regional
Development FEDER funds; Helsinki University Hospital Research Fund;
Academy of Finland [266528]; Finnish Cancer Society; Sigrid Juselius
Foundation; Dutch Cancer Society [NKI1998-1854, NKI2004-3088,
NKI2007-3756]; Netherlands Organization of Scientific Research grant
[NWO 91109024]; Pink Ribbon grant [110005]; BBMRI grant [NWO
184.021.007/CP46]; Hong Kong Hereditary Breast Cancer Family Registry;
Dr. Ellen Li Charitable Foundation, Hong Kong; Hungarian Research Grants
[KTIA-OTKA CK-80745, OTKA K-112228]; Norwegian EEA Financial Mechanism
[Hu0115/NA/2008-3/OP-9]; Asociacion Espanola Contra el Cancer, Spanish
Health Research Fund; Carlos III Health Institute; Catalan Health
Institute and Autonomous Government of Catalonia [ISCIIIRETIC
RD06/0020/1051, RD12/0036/008, PI10/01422, PI10/00748, PI13/00285,
PIE13/00022, 2009SGR290, 2014SGR364]; Canadian Breast Cancer Research
Alliance-grant [019511]; Ministry of Economic Development, Innovation
and Export Trade - grant [PSR-SIIRI-701]; Ministero della Salute and
"5x1000" Istituto Oncologico Veneto grant; Liga Portuguesa Contra o
Cancro; National Breast Cancer Foundation; Queensland Cancer Fund;
Cancer Council of New South Wales; Cancer Council of Victoria; Cancer
Council of Tasmania; Cancer Council of South Australia; Cancer
Foundation of Western Australia; NCI Specialized Program of Research
Excellence (SPORE) in Breast Cancer [CA116201, CA125183, R01 CA142996,
1U01CA161032]; NIH [CA116167, CA128978, CA176785]; MH CZ - DRO (MMCI)
[00209805]; European Regional Development Fund; State Budget of the
Czech Republic (RECAMO) [CZ.1.05/2.1.00/03.0101]; Charles University in
Prague project [UNCE204024]; Robert and Kate Niehaus Clinical Cancer
Genetics Initiative; Andrew Sabin Research Fund; Intramural Research
Program of the US National Cancer Institute, NIH; Westat, Inc,
Rockville, MD [NO2-CP-11019-50, N02-CP-65504]; Russian Federation for
Basic Research [14-04-93959, 15-04-01744]; NRG Oncology Operations grant
[U10 CA180868]; NRG SDMC grant [U10 CA180822]; Gynecologic Oncology
Group (GOG) Administrative Office; GOG Tissue Bank [CA 27469]; GOG
Statistical and Data Center [CA 37517]; Intramural Research Program,
NCI; Ohio State University Comprehensive Cancer Center; ITT (Istituto
Toscano Tumori) grants; Ministry of Science, Technology and Innovation,
Ministry of Higher Education [UM.C/HlR/MOHE/06)]; Cancer Research
Initiatives Foundation; Israel cancer association; funding for the
Israeli Inherited breast cancer consortium; Swedish Cancer Society;
Ralph and Marion Falk Medical Research Trust; Entertainment Industry
Fund National Women's Cancer Research Alliance; Jonsson Comprehensive
Cancer Center Foundation; UCSF Cancer Risk Program; Helen Diller Family
Comprehensive Cancer Center; CRUK; National Institutes of Health (NIH)
[R01-CA102776, R01-CA083855]; Susan G. Komen Foundation for the cure;
Basser Research Center for BRCA; Frieda G. and Saul F. Shapira
BRCA-Associated Cancer Research Program; Hackers for Hope Pittsburgh;
Victorian Cancer Agency; Cancer Australia; American Cancer Society Early
Detection Professorship [SIOP-06-258-01-COUN]; National Center for
Advancing Translational Sciences (NCATS) [UL1TR000124]; European
Community [223175]; National Institutes of Health [CA128978];
Post-Cancer GWAS initiative [1U19 CA148537, 1U19 CA148065, 1U19
CA148112]; Department of Defence [W81XWH-10-1-0341]; Canadian Institutes
of Health Research (CIHR); Komen Foundation for the Cure; Ovarian Cancer
Research Fund; [SAF2010-20493]; [5U01CA113916]; [R01CA140323];
[PBZ_KBN_122/P05/2004]
FX This work was supported by grant UM1 CA164920 from the National Cancer
Institute. The content of this manuscript does not necessarily reflect
the views or policies of the National Cancer Institute or any of the
collaborating centers in the Breast Cancer Family Registry (BCFR), nor
does mention of trade names, commercial products, or organizations imply
endorsement by the US Government or the BCFR.; BFBOCC is partly
supported by: Lithuania (BFBOCC-LT): Research Council of Lithuania grant
SEN-18/2015; BIDMC is supported by the Breast Cancer Research
Foundation; BRCA gene mutations and breast cancer in South African women
(BMBSA) was supported by grants from the Cancer Association of South
Africa (CANSA) to Elizabeth J. van Rensburg; SLN was partially supported
by the Morris and Horowitz Families Endowed Professorship.; This work
was partially supported by Spanish Association against Cancer (AECC08),
RTICC 06/0020/1060, FISPI08/1120, Mutua Madrilena Foundation (FMMA) and
SAF2010-20493; City of Hope Clinical Cancer Genetics Community Network
and the Hereditary Cancer Research Registry, supported in part by Award
Number RC4CA153828 (PI: J. Weitzel) from the National Cancer Institute
and the Office of the Director, National Institutes of Health. The
content is solely the responsibility of the authors and does not
necessarily represent the official views of the National Institutes of
Health; Funds from Italian citizens who allocated the 5x1000 share of
their tax payment in support of the Fondazione IRCCS Istituto Nazionale
Tumori, according to Italian laws (INT-Institutional strategic projects
`5x1000') to SM.; The CIMBA data management and data analysis were
supported by Cancer Research UK grants C12292/A20861, C12292/A11174. ACA
is a Cancer Research UK Senior Cancer Research Fellow. GCT is an NHMRC
Senior Principal Research Fellow.; This research has been co-financed by
the European Union (European Social Fund - ESF) and Greek national funds
through the Operational Program "Education and Lifelong Learning" of the
National Strategic Reference Framework (NSRF) - Research Funding Program
of the General Secretariat for Research & Technology: SYN11_10_19 NBCA.
Investing in knowledge society through the European Social Fund.; The
DKFZ study was supported by the DKFZ.; EMBRACE is supported by Cancer
Research UK Grants C1287/A10118 and C1287/A11990. D. Gareth Evans and
Fiona Lalloo are supported by an NIHR grant to the Biomedical Research
Centre, Manchester. The Investigators at The Institute of Cancer
Research and The Royal Marsden NHS Foundation Trust are supported by an
NIHR grant to the Biomedical Research Centre at The Institute of Cancer
Research and The Royal Marsden NHS Foundation Trust. Ros Eeles and
Elizabeth Bancroft are supported by Cancer Research UK Grant
C5047/A8385. Ros Eeles is also supported by NIHR support to the
Biomedical Research Centre at The Institute of Cancer Research and The
Royal Marsden NHS Foundation Trust; The authors acknowledge support from
The University of Kansas Cancer Center (P30 CA168524) and the Kansas
Bioscience Authority Eminent Scholar Program. A.K.G. was funded by
5U01CA113916, R01CA140323, and by the Chancellors Distinguished Chair in
Biomedical Sciences Professorship.; The German Consortium of Hereditary
Breast and Ovarian Cancer (GC-HBOC) is supported by the German Cancer
Aid (grant no 110837), Rita K. Schmutzler) and by the Center for
Molecular Medicine Cologne (CMMC); The study was supported by the Ligue
Nationale Contre le Cancer; the Association "Le cancer du sein,
parlons-en!" Award; the Canadian Institutes of Health Research for the
"CIHR Team in Familial Risks of Breast Cancer" program and the French
National Institute of Cancer (INCa).; CI received support from the
Non-Therapeutic Subject Registry Shared Resource at Georgetown
University (NIH/NCI grant P30-CA051008), the Fisher Center for Familial
Cancer Research, and Swing Fore the Cure.; Was supported by a grant
RD12/0036/0006 and 15/00059 from ISCIII (Spain), partially supported by
European Regional Development FEDER funds; The HEBCS was financially
supported by the Helsinki University Hospital Research Fund, Academy of
Finland (266528), the Finnish Cancer Society and the Sigrid Juselius
Foundation.; The HEBON study is supported by the Dutch Cancer Society
grants NKI1998-1854, NKI2004-3088, NKI2007-3756, the Netherlands
Organization of Scientific Research grant NWO 91109024, the Pink Ribbon
grant 110005 and the BBMRI grant NWO 184.021.007/CP46. HEBON thanks the
registration teams of the Comprehensive Cancer Centre Netherlands and
Comprehensive Centre South (together the Netherlands Cancer Registry)
and PALGA (Dutch Pathology Registry) for part of the data collection.;
HRBCP is supported by The Hong Kong Hereditary Breast Cancer Family
Registry and the Dr. Ellen Li Charitable Foundation, Hong Kong;
Hungarian Breast and Ovarian Cancer Study was supported by Hungarian
Research Grants KTIA-OTKA CK-80745, OTKA K-112228 and the Norwegian EEA
Financial Mechanism Hu0115/NA/2008-3/OP-9; ICO: Contract grant sponsor:
Asociacion Espanola Contra el Cancer, Spanish Health Research Fund;
Carlos III Health Institute; Catalan Health Institute and Autonomous
Government of Catalonia. Contract grant numbers: ISCIIIRETIC
RD06/0020/1051, RD12/0036/008, PI10/01422, PI10/00748, PI13/00285,
PIE13/00022, 2009SGR290 and 2014SGR364.; The IHCC was supported by Grant
PBZ_KBN_122/P05/2004; This work was supported by the Canadian Institutes
of Health Research for the "CIHR Team in Familial Risks of Breast
Cancer" program, the Canadian Breast Cancer Research Alliance-grant
#019511 and the Ministry of Economic Development, Innovation and Export
Trade - grant # PSR-SIIRI-701.; IOCHBOCS is supported by Ministero della
Salute and "5x1000" Istituto Oncologico Veneto grant.; This study was in
part supported by Liga Portuguesa Contra o Cancro.; kConFab is supported
by a grant from the National Breast Cancer Foundation, and previously by
the National Health and Medical Research Council (NHMRC), the Queensland
Cancer Fund, the Cancer Councils of New South Wales, Victoria, Tasmania
and South Australia, and the Cancer Foundation of Western Australia;;
MAYO is supported by NIH grants CA116167, CA128978 and CA176785, an NCI
Specialized Program of Research Excellence (SPORE) in Breast Cancer
(CA116201), a grant from the Breast Cancer Research Foundation, and a
generous gift from the David F. and Margaret T. Grohne Family
Foundation.; MODSQUAD was supported by MH CZ - DRO (MMCI, 00209805) and
by the European Regional Development Fund and the State Budget of the
Czech Republic (RECAMO, CZ.1.05/2.1.00/03.0101) to LF, and by Charles
University in Prague project UNCE204024 (MZ).; MSKCC is supported by
grants from the Breast Cancer Research Foundation, the Robert and Kate
Niehaus Clinical Cancer Genetics Initiative, and the Andrew Sabin
Research Fund.; The research of Drs. MH Greene and PL Mai was supported
by the Intramural Research Program of the US National Cancer Institute,
NIH, and by support services contracts NO2-CP-11019-50 and N02-CP-65504
with Westat, Inc, Rockville, MD. For CIMBA PRS paper: The research of
Drs. MH Greene and JT Loud was supported by the Intramural Research
Program of the US National Cancer Institute, NIH, and by support
services contracts NO2-CP-11019-50 and N02-CP-65504 with Westat, Inc,
Rockville, MD.; This work has been supported by the Russian Federation
for Basic Research (grants 14-04-93959 and 15-04-01744).; This study was
supported by NRG Oncology Operations grant number U10 CA180868 as well
as NRG SDMC grant U10 CA180822, Gynecologic Oncology Group (GOG)
Administrative Office and the GOG Tissue Bank (CA 27469) and the GOG
Statistical and Data Center (CA 37517). Drs. Greene, Mai and Savage were
supported by funding from the Intramural Research Program, NCI.; OSUCCG
is supported by the Ohio State University Comprehensive Cancer Center.;
This work was supported by the ITT (Istituto Toscano Tumori) grants
2011-2013.; Ministry of Science, Technology and Innovation, Ministry of
Higher Education (UM.C/HlR/MOHE/06) and Cancer Research Initiatives
Foundation; This project was partially funded through a grant by the
Israel cancer association and the funding for the Israeli Inherited
breast cancer consortium; SWE-BRCA collaborators are supported by the
Swedish Cancer Society; UCHICAGO is supported by NCI Specialized Program
of Research Excellence (SPORE) in Breast Cancer (CA125183), R01
CA142996, 1U01CA161032 and by the Ralph and Marion Falk Medical Research
Trust, the Entertainment Industry Fund National Women's Cancer Research
Alliance and the Breast Cancer research Foundation. OIO is an ACS
Clinical Research Professor.; Jonsson Comprehensive Cancer Center
Foundation; Breast Cancer Research Foundation; UCSF Cancer Risk Program
and Helen Diller Family Comprehensive Cancer Center; UKFOCR was
supported by a project grant from CRUK to Paul Pharoah.; National
Institutes of Health (NIH) (R01-CA102776 and R01-CA083855; Breast Cancer
Research Foundation; Susan G. Komen Foundation for the cure, Basser
Research Center for BRCA; Frieda G. and Saul F. Shapira BRCA-Associated
Cancer Research Program; Hackers for Hope Pittsburgh; Victorian Cancer
Agency, Cancer Australia, National Breast Cancer Foundation; Dr Karlan
is funded by the American Cancer Society Early Detection Professorship
(SIOP-06-258-01-COUN) and the National Center for Advancing
Translational Sciences (NCATS), Grant UL1TR000124; Funding for the iCOGS
infrastructure came from: the European Community's Seventh Framework
Programme under grant agreement no 223175 (HEALTH-F2-2009-223175)
(COGS), Cancer Research UK (C1287/A10118, C1287/A 10710, C12292/A11174,
C1281/A12014, C5047/A8384, C5047/A15007, C5047/A10692, C8197/A16565),
the National Institutes of Health (CA128978) and Post-Cancer GWAS
initiative (1U19 CA148537, 1U19 CA148065 and 1U19 CA148112 - the GAME-
ON initiative), the Department of Defence (W81XWH-10-1-0341), the
Canadian Institutes of Health Research (CIHR) for the CIHR Team in
Familial Risks of Breast Cancer, Komen Foundation for the Cure, the
Breast Cancer Research Foundation, and the Ovarian Cancer Research Fund
NR 39
TC 1
Z9 1
U1 10
U2 10
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1465-542X
EI 1465-5411
J9 BREAST CANCER RES
JI Breast Cancer Res.
PD NOV 11
PY 2016
VL 18
AR 112
DI 10.1186/s13058-016-0768-3
PG 19
WC Oncology
SC Oncology
GA EG2UM
UT WOS:000390899600001
PM 27836010
ER
PT J
AU Gladyshev, VN
Arner, ES
Berry, MJ
Brigelius-Flohe, R
Bruford, EA
Burk, RF
Carlson, BA
Castellano, S
Chavatte, L
Conrad, M
Copeland, PR
Diamond, AM
Driscoll, DM
Ferreiro, A
Flohe, L
Green, FR
Guigo, R
Handy, DE
Hatfield, DL
Hesketh, J
Hoffmann, PR
Holmgren, A
Hondal, RJ
Howard, MT
Huang, K
Kim, HY
Kim, IY
Kohrle, J
Krol, A
Kryukov, GV
Lee, BJ
Lee, BC
Lei, XG
Liu, Q
Lescure, A
Lobanov, AV
Loscalzo, J
Maiorino, M
Mariotti, M
Prabhu, KS
Rayman, MP
Rozovsky, S
Salinas, G
Schmidt, EE
Schomburg, L
Schweizer, U
Simonovic, M
Sunde, RA
Tsuji, PA
Tweedie, S
Ursini, F
Whanger, PD
Zhang, Y
AF Gladyshev, Vadim N.
Arner, Elias S.
Berry, Marla J.
Brigelius-Flohe, Regina
Bruford, Elspeth A.
Burk, Raymond F.
Carlson, Bradley A.
Castellano, Sergi
Chavatte, Laurent
Conrad, Marcus
Copeland, Paul R.
Diamond, Alan M.
Driscoll, Donna M.
Ferreiro, Ana
Flohe, Leopold
Green, Fiona R.
Guigo, Roderic
Handy, Diane E.
Hatfield, Dolph L.
Hesketh, John
Hoffmann, Peter R.
Holmgren, Arne
Hondal, Robert J.
Howard, Michael T.
Huang, Kaixun
Kim, Hwa-Young
Kim, Ick Young
Koehrle, Josef
Krol, Alain
Kryukov, Gregory V.
Lee, Byeong Jae
Lee, Byung Cheon
Lei, Xin Gen
Liu, Qiong
Lescure, Alain
Lobanov, Alexei V.
Loscalzo, Joseph
Maiorino, Matilde
Mariotti, Marco
Sandeep Prabhu, K.
Rayman, Margaret P.
Rozovsky, Sharon
Salinas, Gustavo
Schmidt, Edward E.
Schomburg, Lutz
Schweizer, Ulrich
Simonovic, Miljan
Sunde, Roger A.
Tsuji, Petra A.
Tweedie, Susan
Ursini, Fulvio
Whanger, Philip D.
Zhang, Yan
TI Selenoprotein Gene Nomenclature
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
DE genomics; selenium; selenocysteine; selenoprotein; structure-function;
function; gene name; nomenclature
ID HYDROPEROXIDE GLUTATHIONE-PEROXIDASE; AMINO-ACID-SEQUENCE; THIOREDOXIN
REDUCTASE; RAT-LIVER; IODOTHYRONINE 5-DEIODINASE; EUKARYOTIC
SELENOPROTEINS; SELENIUM METABOLISM; CONTAINING PROTEINS; MESSENGER-RNA;
SELENOCYSTEINE
AB The human genome contains 25 genes coding for selenocysteine-containing proteins (selenoproteins). These proteins are involved in a variety of functions, most notably redox homeostasis. Selenoprotein enzymes with known functions are designated according to these functions: TXNRD1, TXNRD2, and TXNRD3 (thioredoxin reductases), GPX1, GPX2, GPX3, GPX4, and GPX6 (glutathione peroxidases), DIO1, DIO2, and DIO3 (iodothyronine deiodinases), MSRB1 (methionine sulfoxide reductase B1), and SEPHS2 (selenophosphate synthetase 2). Selenoproteins without known functions have traditionally been denoted by SEL or SEP symbols. However, these symbols are sometimes ambiguous and conflict with the approved nomenclature for several other genes. Therefore, there is a need to implement a rational and coherent nomenclature system for selenoprotein-encoding genes. Our solution is to use the root symbol SELENO followed by a letter. This nomenclature applies to SELENOF (selenoprotein F, the 15-kDa selenoprotein, SEP15), SELENOH (selenoprotein H, SELH, C11orf31), SELENOI (selenoprotein I, SELI, EPT1), SELENOK (selenoprotein K, SELK), SELENOM (selenoprotein M, SELM), SELENON (selenoprotein N, SEPN1, SELN), SELENOO (selenoprotein O, SELO), SELENOP (selenoprotein P, SeP, SEPP1, SELP), SELENOS (selenoprotein S, SELS, SEPS1, VIMP), SELENOT (selenoprotein T, SELT), SELENOV (selenoprotein V, SELV), and SELENOW (selenoprotein W, SELW, SEPW1). This system, approved by the HUGO Gene Nomenclature Committee, also resolves conflicting, missing, and ambiguous designations for selenoprotein genes and is applicable to selenoproteins across vertebrates.
C1 [Gladyshev, Vadim N.; Lobanov, Alexei V.; Mariotti, Marco] Harvard Med Sch, Brigham & Womens Hosp, Div Genet, Dept Med, Boston, MA 02115 USA.
[Gladyshev, Vadim N.] Broad Inst Harvard & MIT, Cambridge, MA 02142 USA.
[Arner, Elias S.; Holmgren, Arne] Karolinska Inst, Div Biochem, Dept Med Biochem & Biophys MBB, SE-17177 Stockholm, Sweden.
[Berry, Marla J.; Hoffmann, Peter R.] Univ Hawaii Manoa, John A Burns Sch Med, Dept Cell & Mol Biol, Honolulu, HI 96813 USA.
[Brigelius-Flohe, Regina] German Inst Human Nutr Potsdam Rehbrucke, D-14558 Nuthetal, Germany.
[Bruford, Elspeth A.; Tweedie, Susan] HUGOGene Nomenclature Comm HGNC, European Bioinformat Inst European Mol Biol Lab E, Hinxton CB10 1SD, England.
[Burk, Raymond F.] Vanderbilt Univ, Div Gastroenterol Hepatol & Nutr, Dept Med, Sch Med, Nashville, TN 37232 USA.
[Carlson, Bradley A.; Hatfield, Dolph L.] Ctr Canc Res, NIH, Mouse Canc Genet Program, Mol Biol Selenium Sect, Bethesda, MD 20892 USA.
[Castellano, Sergi] Max Planck Inst Evolutionary Anthropol, Dept Evolutionary Genet, D-04103 Leipzig, Germany.
[Chavatte, Laurent] INSERM, CIRI, U1111, F-69007 Lyon, France.
[Chavatte, Laurent] CNRS, ENS UMR5308, F-69007 Lyon, France.
[Conrad, Marcus] Helmholtz Zentrum Munchen, Inst Dev Genet, D-85764 Neuherberg, Germany.
[Copeland, Paul R.] Rutgers Robert Wood Johnson Med Sch, Dept Biochem & Mol Biol, Piscataway, NJ 08854 USA.
[Diamond, Alan M.] Univ Illinois, Dept Pathol, Chicago, IL 60607 USA.
[Driscoll, Donna M.] Cleveland Clin Fdn, Dept Cellular & Mol Med, Lerner Res Inst, Cleveland, OH 44195 USA.
[Ferreiro, Ana] Univ Paris Diderot, Sorbonne Paris Cite, Pathophysiol Striated Muscles Lab, Unit Funct & Adapt Biol BFA,UMR CNRS 8251 BFA, F-75250 Paris, France.
[Ferreiro, Ana] Grp Hosp Pitie Salpetriere, AP HP, Ctr Reference Malad Neuromusculaires Paris Est, F-75013 Paris, France.
[Flohe, Leopold] Univ Republica, Facultad Med, Dept Bioquim, Montevideo 11800, Uruguay.
[Flohe, Leopold] Univ Padua, Dept Mol Med, I-35121 Padua, Italy.
[Green, Fiona R.] Univ Manchester, Div Cardiovasc Sci, Sch Med Sci, Fac Biol Med & Hlth, Manchester, Lancs, England.
[Guigo, Roderic] Ctr Genom Regulat CRG, Barcelona 08003, Spain.
[Guigo, Roderic] UPF, Barcelona 08002, Spain.
[Handy, Diane E.] Brigham & Womens Hosp, Dept Med, Cardiovasc Div, Boston, MA 02115 USA.
[Handy, Diane E.] Harvard Med Sch, Boston, MA 02115 USA.
[Hesketh, John] Newcastle Univ, Inst Cell & Mol Biosci, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England.
[Hesketh, John] Newcastle Univ, Human Nutr Res Ctr, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England.
[Hesketh, John] Newcastle Univ, Sch Med, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England.
[Hondal, Robert J.] Univ Vermont, Dept Biochem, Burlington, VT 05405 USA.
[Howard, Michael T.] Univ Utah, Dept Human Genet, Salt Lake City, UT 84112 USA.
[Huang, Kaixun] Huazhong Univ Sci & Technol, Hubei Key Lab Bioinorgan Chem & Mat Med, Sch Chem & Chem Engn, Wuhan 430074, Peoples R China.
[Kim, Hwa-Young] Yeungnam Univ, Dept Biochem & Mol Biol, Coll Med, Daegu 42415, South Korea.
[Kim, Ick Young; Lee, Byung Cheon] Korea Univ, Coll Life Sci & Biotechnol, Seoul 02841, South Korea.
[Koehrle, Josef; Schomburg, Lutz] Charite, Inst Expt Endocrinol, D-13353 Berlin, Germany.
[Krol, Alain; Lescure, Alain] Univ Strasbourg, Architecture & Reactivite ARN, Ctr Natl Rech Sci, Inst Biol Mol & Cellulaire, F-67084 Strasbourg, France.
[Kryukov, Gregory V.] KSQ Therapeut, Cambridge, MA 02139 USA.
[Lee, Byeong Jae] Seoul Natl Univ, Sch Biol Sci, Seoul 151742, South Korea.
[Lei, Xin Gen] Cornell Univ, Dept Anim Sci, Ithaca, NY 14853 USA.
[Liu, Qiong; Zhang, Yan] Shenzhen Univ, Shenzhen Key Lab Marine Biotechnol & Ecol, Coll Life Sci, Shenzhen 518060, Guangdong Provi, Peoples R China.
[Lescure, Alain] Ctr Natl Rech Sci, F-75794 Paris, France.
[Loscalzo, Joseph] Harvard Med Sch, Dept Med, Brigham & Womens Hosp, Boston, MA 02115 USA.
[Sandeep Prabhu, K.] Penn State Univ, Dept Vet & Biomed Sci, University Pk, PA 16802 USA.
[Rayman, Margaret P.] Univ Surrey, Dept Nut Sci, Fac Hlth & Med Sci, Guildford GU2 7XH, Surrey, England.
[Rozovsky, Sharon] Univ Delaware, Dept Chem & Biochem, Newark, DE 19716 USA.
[Salinas, Gustavo] Inst Higiene, Catedra Inmunol, Fac Quim, Montevideo 11600, Uruguay.
[Schmidt, Edward E.] Montana State Univ, Dept Microbiol & Immunol, Bozeman, MT 59717 USA.
[Schweizer, Ulrich] Rhein Friedrich Wilhelms Univ Bonn, Inst Biochem & Molekularbiol, D-53115 Bonn, Germany.
[Simonovic, Miljan] Univ Illinois, Dept Biochem & Mol Genet, Chicago, IL 60607 USA.
[Sunde, Roger A.] Univ Wisconsin, Dept Nutr Sci, Madison, WI 53706 USA.
[Tsuji, Petra A.] Towson Univ, Dept Biol Sci, Towson, MD 21252 USA.
[Whanger, Philip D.] Oregon State Univ, Dept Environm & Mol Toxicol, Coll Agr Sci, Corvallis, OR 97331 USA.
RP Gladyshev, VN (reprint author), Harvard Med Sch, Brigham & Womens Hosp, Div Genet, Dept Med, Boston, MA 02115 USA.; Gladyshev, VN (reprint author), Broad Inst Harvard & MIT, Cambridge, MA 02142 USA.
EM vgladyshev@rics.bwh.harvard.edu
RI Guigo, Roderic/D-1303-2010; rozovsky, sharon/S-4534-2016;
OI Guigo, Roderic/0000-0002-5738-4477; rozovsky,
sharon/0000-0003-4902-0777; Kohrle, Josef/0000-0002-9187-9078; Arner,
Elias/0000-0002-4807-6114
FU National Institutes of Health [GM061603]
FX This work was supported, in whole or in part, by National Institutes of
Health Grant GM061603. The authors declare that they have no conflicts
of interest with the contents of this article. The content is solely the
responsibility of the authors and does not necessarily represent the
official views of the National Institutes of Health.
NR 49
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U1 15
U2 15
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
EI 1083-351X
J9 J BIOL CHEM
JI J. Biol. Chem.
PD NOV 11
PY 2016
VL 291
IS 46
BP 24036
EP 24040
DI 10.1074/jbc.M116.756155
PG 5
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA EC9XR
UT WOS:000388498100020
PM 27645994
ER
PT J
AU Sharma, AK
Arora, D
Singh, LK
Gangwal, A
Sajid, A
Molle, V
Singh, Y
Nandicoori, VK
AF Sharma, Aditya K.
Arora, Divya
Singh, Lalit K.
Gangwal, Aakriti
Sajid, Andaleeb
Molle, Virginie
Singh, Yogendra
Nandicoori, Vinay Kumar
TI Serine/Threonine Protein Phosphatase PstP of Mycobacterium tuberculosis
Is Necessary for Accurate Cell Division and Survival of Pathogen
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
DE cell division; cell signaling; mycobacteria; Mycobacterium tuberculosis;
phosphatase; phosphorylation; protein serine; threonine phosphatase
(PSP); PstP; cell division
ID 2-COMPONENT SIGNAL-TRANSDUCTION; VACUOLAR-H+-ATPASE;
CORYNEBACTERIUM-GLUTAMICUM; TYROSINE PHOSPHATASES; BACILLUS-ANTHRACIS;
GENOME SEQUENCE; GENE-EXPRESSION; KINASES PKNA; IN-VITRO;
PHOSPHORYLATION
AB Protein phosphatases play vital roles in phosphorylation-mediated cellular signaling. Although there are 11 serine/threonine protein kinases in Mycobacterium tuberculosis, only one serine/threonine phosphatase, PstP, has been identified. Although PstP has been biochemically characterized and multiple in vitro substrates have been identified, its physiological role has not yet been elucidated. In this study, we have investigated the impact of PstP on cell growth and survival of the pathogen in the host. Overexpression of PstP led to elongated cells and partially compromised survival. We find that depletion of PstP is detrimental to cell survival, eventually leading to cell death. PstP depletion results in elongated multiseptate cells, suggesting a role for PstP in regulating cell division events. Complementation experiments performed with PstP deletion mutants revealed marginally compromised survival, suggesting that all of the domains, including the extracellular domain, are necessary for complete rescue. On the other hand, the catalytic activity of PstP is absolutely essential for the in vitro growth. Mice infection experiments establish a definitive role for PstP in pathogen survival within the host. Depletion of PstP from established infections causes pathogen clearance, indicating that the continued presence of PstP is necessary for pathogen survival. Taken together, our data suggest an important role for PstP in establishing and maintaining infection, possibly via the modulation of cell division events.
C1 [Arora, Divya; Nandicoori, Vinay Kumar] Natl Inst Immunol, Aruna Asaf Ali Marg, New Delhi 110067, India.
[Sharma, Aditya K.; Singh, Lalit K.; Sajid, Andaleeb; Singh, Yogendra] CSIR Inst Genom & Integrat Biol, Mall Rd, Delhi 110007, India.
[Gangwal, Aakriti; Singh, Yogendra] Univ Delhi, Dept Zool, Delhi 110007, India.
[Molle, Virginie] Univ Montpellier 2, CNRS, Lab Dynam Interact Membranaires Normales & Pathol, UMR 5235, Montpellier, France.
[Sharma, Aditya K.] CSIR IGIB, Acad Sci & Innovat Res AcSIR, Delhi 110025, India.
[Sajid, Andaleeb] NIAID, NIH, Bethesda, MD 20814 USA.
RP Nandicoori, VK (reprint author), Natl Inst Immunol, Aruna Asaf Ali Marg, New Delhi 110067, India.; Singh, Y (reprint author), CSIR Inst Genom & Integrat Biol, Mall Rd, Delhi 110007, India.; Singh, Y (reprint author), Univ Delhi, Dept Zool, Delhi 110007, India.
EM ysingh@igib.res.in; vinaykn@nii.ac.in
FU Indo French Centre for the Promotion of Advanced Research Grant [5303-1,
BSC0104]
FX This work was supported by Indo French Centre for the Promotion of
Advanced Research Grant 5303-1 (to V.K.N., Y.S., and V.M.) and BSC0104
(CSIR) (to Y.S.). The authors declare that they have no conflicts of
interest with the contents of this article.
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PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
EI 1083-351X
J9 J BIOL CHEM
JI J. Biol. Chem.
PD NOV 11
PY 2016
VL 291
IS 46
BP 24215
EP 24230
DI 10.1074/jbc.M116.754531
PG 16
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA EC9XR
UT WOS:000388498100035
PM 27758870
ER
PT J
AU Sassa, A
Caglayan, M
Rodriguez, Y
Beard, WA
Wilson, SH
Nohmi, T
Honma, M
Yasui, M
AF Sassa, Akira
Caglayan, Melike
Rodriguez, Yesenia
Beard, William A.
Wilson, Samuel H.
Nohmi, Takehiko
Honma, Masamitsu
Yasui, Manabu
TI Impact of Ribonucleotide Backbone on Translesion Synthesis and Repair of
7,8-Dihydro-8-oxoguanine
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
DE 8-oxoguanine (8-oxoG); base excision repair (BER); DNA damage; DNA
polymerase; oxidative stress; ribonucleotide; translesion DNA synthesis
ID DNA-POLYMERASE-KAPPA; IN-VITRO; EXCISION-REPAIR; LESION BYPASS;
ERROR-FREE; HUMAN-CELLS; ETA; EXTENSION; 8-OXOGUANINE; SUBSTRATE
AB Numerous ribonucleotides are incorporated into the genome during DNA replication. Oxidized ribonucleotides can also be erroneously incorporated into DNA. Embedded ribonucleotides destabilize the structure of DNA and retard DNA synthesis by DNA polymerases (pols), leading to genomic instability. Mammalian cells possess translesion DNA synthesis (TLS) pols that bypass DNA damage. The mechanism of TLS and repair of oxidized ribonucleotides remains to be elucidated. To address this, we analyzed the miscoding properties of the ribonucleotides riboguanosine (rG) and 7,8-dihydro-8-oxo-riboguanosine (8-oxo-rG) during TLS catalyzed by the human TLS pols and in vitro. The primer extension reaction catalyzed by human replicative pol was strongly blocked by 8-oxo-rG. pol inefficiently bypassed rG and 8-oxo-rG compared with dG and 7,8-dihydro-8-oxo-2-deoxyguanosine (8-oxo-dG), whereas pol easily bypassed the ribonucleotides. pol exclusively inserted dAMP opposite 8-oxo-rG. Interestingly, pol preferentially inserted dCMP opposite 8-oxo-rG, whereas the insertion of dAMP was favored opposite 8-oxo-dG. In addition, pol accurately bypassed 8-oxo-rG. Furthermore, we examined the activity of the base excision repair (BER) enzymes 8-oxoguanine DNA glycosylase (OGG1) and apurinic/apyrimidinic endonuclease 1 on the substrates, including rG and 8-oxo-rG. Both BER enzymes were completely inactive against 8-oxo-rG in DNA. However, OGG1 suppressed 8-oxo-rG excision by RNase H2, which is involved in the removal of ribonucleotides from DNA. These results suggest that the different sugar backbones between 8-oxo-rG and 8-oxo-dG alter the capacity of TLS and repair of 8-oxoguanine.
C1 [Sassa, Akira; Nohmi, Takehiko; Honma, Masamitsu; Yasui, Manabu] Natl Inst Hlth Sci, Div Genet & Mutagenesis, Setagaya Ku, 1-18-1 Kamiyoga, Tokyo 1588501, Japan.
[Caglayan, Melike; Rodriguez, Yesenia; Beard, William A.; Wilson, Samuel H.] NIEHS, Genome Integr & Struct Biol Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.
RP Sassa, A; Yasui, M (reprint author), Natl Inst Hlth Sci, Div Genet & Mutagenesis, Setagaya Ku, 1-18-1 Kamiyoga, Tokyo 1588501, Japan.
EM a-sassa@nihs.go.jp; m-yasui@nihs.go.jp
FU Ministry of Education, Culture, Sports, Science and Technology in Japan
[16K16195, 25281022]; Intramural Research Program of the National
Institutes of Health, NIEHS [Z01 ES050158, Z01 ES050159]
FX This work was supported by Grant-in-Aid for Young Scientists B
(16K16195) and for Scientific Research B (25281022) from the Ministry of
Education, Culture, Sports, Science and Technology in Japan and the
Intramural Research Program of the National Institutes of Health, NIEHS
Grants Z01 ES050158 and Z01 ES050159. The authors declare that they have
no conflicts of interest with the contents of this article. The content
is solely the responsibility of the authors and does not necessarily
represent the official views of the National Institutes of Health.
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PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
EI 1083-351X
J9 J BIOL CHEM
JI J. Biol. Chem.
PD NOV 11
PY 2016
VL 291
IS 46
BP 24314
EP 24323
DI 10.1074/jbc.M116.738732
PG 10
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA EC9XR
UT WOS:000388498100042
PM 27660390
ER
PT J
AU Young, DJ
Guydosh, NR
AF Young, David J.
Guydosh, Nicholas R.
TI UNFOLDED PROTEIN RESPONSE Silence without stress
SO ELIFE
LA English
DT Editorial Material
ID TRANSCRIPTION FACTOR; ENDOPLASMIC-RETICULUM; TRANSLATION
C1 [Young, David J.; Guydosh, Nicholas R.] NIDDK, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA.
RP Guydosh, NR (reprint author), NIDDK, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA.
EM nicholas.guydosh@nih.gov
NR 9
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U1 1
U2 1
PU ELIFE SCIENCES PUBLICATIONS LTD
PI CAMBRIDGE
PA SHERATON HOUSE, CASTLE PARK, CAMBRIDGE, CB3 0AX, ENGLAND
SN 2050-084X
J9 ELIFE
JI eLife
PD NOV 11
PY 2016
VL 5
AR e22073
DI 10.7554/eLife.22073
PG 3
WC Biology
SC Life Sciences & Biomedicine - Other Topics
GA EC9YV
UT WOS:000388501100001
ER
PT J
AU Joshi, AA
Lerman, JB
Aberra, TM
Afshar, M
Teague, HL
Rodante, JA
Krishnamoorthy, P
Ng, Q
Aridi, TZ
Salahuddin, T
Natarajan, B
Lockshin, BN
Ahlman, MA
Chen, MY
Rader, DJ
Reilly, MP
Remaley, AT
Bluemke, DA
Playford, MP
Gelfand, JM
Mehta, NN
AF Joshi, Aditya A.
Lerman, Joseph B.
Aberra, Tsion M.
Afshar, Mehdi
Teague, Heather L.
Rodante, Justin A.
Krishnamoorthy, Parasuram
Ng, Qimin
Aridi, Tarek Z.
Salahuddin, Taufiq
Natarajan, Balaji
Lockshin, Benjamin N.
Ahlman, Mark A.
Chen, Marcus Y.
Rader, Daniel J.
Reilly, Muredach P.
Remaley, Alan T.
Bluemke, David A.
Playford, Martin P.
Gelfand, Joel M.
Mehta, Nehal N.
TI GlycA Is a Novel Biomarker of Inflammation and Subclinical
Cardiovascular Disease in Psoriasis
SO CIRCULATION RESEARCH
LA English
DT Article
DE cardiovascular disease; coronary artery disease; FDG PET CT; GlycA;
inflammation; psoriasis; risk factors
ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; COMPUTED TOMOGRAPHIC ANGIOGRAPHY;
POSITRON-EMISSION-TOMOGRAPHY; ACUTE-PHASE GLYCOPROTEINS; TYPE-2
DIABETES-MELLITUS; ACUTE CORONARY SYNDROME; C-REACTIVE PROTEIN;
FDG-PET/CT; VASCULAR INFLAMMATION; RISK
AB Rationale: GlycA, an emerging inflammatory biomarker, predicted cardiovascular events in population-based studies. Psoriasis, an inflammatory disease associated with increased cardiovascular risk, provides a model to study inflammatory biomarkers in cardiovascular disease (CVD). Whether GlycA associates with psoriasis and how it predicts subclinical CVD beyond high-sensitivity C-reactive protein in psoriasis is unknown.
Objective: To investigate the relationships between GlycA and psoriasis and between GlycA and subclinical CVD.
Methods and Results: Patients with psoriasis and controls (n=412) participated in a 2-stage study. We measured GlycA by nuclear magnetic resonance spectroscopy. National Institutes of Health (NIH) participants underwent 18-F Fluorodeoxyglucose Positron Emission Tomography Computed Tomography (18-FDG PET/CT) scans to assess vascular inflammation (VI) and coronary computed tomographic angiography to quantify coronary artery disease burden. Psoriasis cohorts were young (mean age=47.9), with low cardiovascular risk and moderate skin disease. high-sensitivity C-reactive protein and GlycA were increased in psoriasis compared with controls (GlycA: [PENN: 408.8 +/- 75.4 versus 289.4 +/- 60.2, P<0.0001; NIH: 415.8 +/- 63.2 versus 346.2 +/- 46, P<0.0001]) and demonstrated a doseresponse with psoriasis severity. In stage 2, VI (beta=0.36, P<0.001) and coronary artery disease (beta=0.29, P=0.004) associated with GlycA beyond CV risk factors in psoriasis. In receiver operating characteristic analysis, GlycA added value in predicting VI (P=0.01) and coronary artery disease (P<0.01). Finally, initiating anti-tumor necrosis factor therapy (n=16) reduced psoriasis severity (P<0.001), GlycA (463.7 +/- 92.5 versus 370.1 +/- 78.5, P<0.001) and VI (1.93 +/- 0.36 versus 1.76 +/- 0.19, P<0.001), whereas GlycA remained associated with VI (beta=0.56, P<0.001) post treatment.
Conclusions: GlycA associated with psoriasis severity and subclinical CVD beyond traditional CV risk and highsensitivity C-reactive protein. Moreover, psoriasis treatment reduced GlycA and VI. These findings support the potential use of GlycA in subclinical CVD risk assessment in psoriasis and potentially other inflammatory diseases.
C1 [Joshi, Aditya A.; Lerman, Joseph B.; Aberra, Tsion M.; Teague, Heather L.; Rodante, Justin A.; Ng, Qimin; Aridi, Tarek Z.; Salahuddin, Taufiq; Natarajan, Balaji; Chen, Marcus Y.; Remaley, Alan T.; Bluemke, David A.; Playford, Martin P.; Mehta, Nehal N.] NHLBI, Cardiovasc & Pulm Branch, Bldg 10, Bethesda, MD 20892 USA.
[Joshi, Aditya A.; Lerman, Joseph B.; Aberra, Tsion M.; Teague, Heather L.; Rodante, Justin A.; Ng, Qimin; Aridi, Tarek Z.; Salahuddin, Taufiq; Natarajan, Balaji; Remaley, Alan T.; Playford, Martin P.; Mehta, Nehal N.] NHLBI, Sect Inflammat & Cardiometab Dis, Bldg 10, Bethesda, MD 20892 USA.
[Joshi, Aditya A.] Allegheny Gen Hosp, Dept Internal Med, Pittsburgh, PA 15212 USA.
[Afshar, Mehdi] McGill Univ, Dept Med, Montreal, PQ, Canada.
[Krishnamoorthy, Parasuram] Albert Einstein Med Ctr, Einstein Inst Heart & Vasc Hlth, Dept Cardiol, Philadelphia, PA 19141 USA.
[Salahuddin, Taufiq] Univ Colorado, Dept Internal Med, Denver, CO USA.
[Natarajan, Balaji] Univ Arizona, Coll Med South Campus, Dept Internal Med, Tucson, AZ USA.
[Lockshin, Benjamin N.] Derm Associates, Silver Spring, MD USA.
[Ahlman, Mark A.] NIH, Dept Radiol & Imaging Sci, Clin Res Ctr, Bldg 10, Bethesda, MD 20892 USA.
[Rader, Daniel J.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Gelfand, Joel M.] Univ Penn, Dept Dermatol, Philadelphia, PA 19104 USA.
[Gelfand, Joel M.] Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA.
[Reilly, Muredach P.] Columbia Univ, Dept Med, Div Cardiol, Irving Inst Clin & Translat Res, New York, NY USA.
RP Mehta, NN (reprint author), NHLBI, Sect Inflammat & Cardiometab Dis, Clin Res Ctr, 10 Ctr Dr,Room 5-5140, Bethesda, MD 20892 USA.
EM nehal.mehta@nih.gov
OI Bluemke, David/0000-0002-8323-8086
FU National Institutes of Health (NIH)
FX The study was supported by the National Institutes of Health (NIH)
intramural research program.
NR 41
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U1 5
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0009-7330
EI 1524-4571
J9 CIRC RES
JI Circ.Res.
PD NOV 11
PY 2016
VL 119
IS 11
BP 1242
EP +
DI 10.1161/CIRCRESAHA.116.309637
PG 15
WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular
Disease
SC Cardiovascular System & Cardiology; Hematology
GA EC4NN
UT WOS:000388108900018
PM 27654120
ER
PT J
AU Henley, SJ
Thomas, CC
Sharapova, SR
Momin, B
Massetti, GM
Winn, DM
Armour, BS
Richardson, LC
AF Henley, S. Jane
Thomas, Cheryll C.
Sharapova, Saida R.
Momin, Behnoosh
Massetti, Greta M.
Winn, Deborah M.
Armour, Brian S.
Richardson, Lisa C.
TI Vital Signs: Disparities in Tobacco-Related Cancer Incidence and
Mortality - United States, 2004-2013
SO MMWR-MORBIDITY AND MORTALITY WEEKLY REPORT
LA English
DT Article
ID AFFORDABLE CARE ACT; SMOKING; DEATHS
AB Background: Tobacco use causes at least 12 types of cancer and is the leading preventable cause of cancer..
Methods: Data from the United States Cancer Statistics dataset for 2004-2013 were used to assess incidence and death rates and trends for cancers that can be caused by tobacco use (tobacco-related cancers: oral cavity and pharynx; esophagus; stomach; colon and rectum; liver; pancreas; larynx; lung, bronchus, and trachea; kidney and renal pelvis; urinary bladder; cervix; and acute myeloid leukemia) by sex, age, race, ethnicity; state, county-level poverty and educational attainment, and cancer site:
Results: Each year during 2009-2013, on average, 660,000 persons in the United States received a diagnosis of a tobacco-related cancer, and 343,000 persons died from these cancers. Tobacco-related cancer incidence and death rates were higher among men than women; highest among black men and women; higher in counties with low proportion of college graduates or high level of poverty; lowest in the West; and differed two-fold among states. During 2004-2013, incidence of tobacco-related cancer decreased 1.3% per year and mortality decreased 1.6% per year, with decreases observed across most groups, hot not at the same rate.
Conclusions: Tobacco-related cancer declined during 2004-2013. However, the burden remains high, and disparities persist among certain groups with higher rates or slower declines in rates.
Implications far Public Health Practice: The burden of tobacco-related cancers can be reduced through efforts to prevent and control tobacco use and other comprehensive cancer control efforts focused on reducing cancer risk, detecting cancer early, improving cancer treatments, helping more persons survive cancer, and improving cancer survivors' quality of life, and better assisting communities disproportionately impacted by cancer.
C1 [Henley, S. Jane; Thomas, Cheryll C.; Momin, Behnoosh; Massetti, Greta M.; Richardson, Lisa C.] CDC, Div Canc Prevent & Control, Atlanta, GA 30333 USA.
[Sharapova, Saida R.; Armour, Brian S.] CDC, Off Smoking & Hlth, Atlanta, GA 30333 USA.
[Winn, Deborah M.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
RP Henley, SJ (reprint author), CDC, Div Canc Prevent & Control, Atlanta, GA 30333 USA.
EM shenley@cdc.gov
NR 15
TC 0
Z9 0
U1 1
U2 1
PU CENTERS DISEASE CONTROL
PI ATLANTA
PA 1600 CLIFTON RD, ATLANTA, GA 30333 USA
SN 0149-2195
EI 1545-861X
J9 MMWR-MORBID MORTAL W
JI MMWR-Morb. Mortal. Wkly. Rep.
PD NOV 11
PY 2016
VL 65
IS 44
BP 1212
EP 1218
PG 7
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA EC3XJ
UT WOS:000388060100003
PM 27832048
ER
PT J
AU Vallabhaneni, S
Kallen, A
Tsay, S
Chow, N
Welsh, R
Kerins, J
Kemble, SK
Pacilli, M
Black, SR
Landon, E
Ridgway, J
Palmore, TN
Zelzany, A
Adams, EH
Quinn, M
Chaturvedi, S
Greenko, J
Fernandez, R
Southwick, K
Furuya, EY
Calfee, DP
Hamula, C
Patel, G
Barrett, P
Lafaro, P
Berkow, EL
Moulton-Meissner, H
Noble-Wang, J
Fagan, RP
Jackson, BR
Lockhart, SR
Litvintseva, AP
Chiller, TM
AF Vallabhaneni, Snigdha
Kallen, Alex
Tsay, Sharon
Chow, Nancy
Welsh, Rory
Kerins, Janna
Kemble, Sarah K.
Pacilli, Massimo
Black, Stephanie R.
Landon, Emily
Ridgway, Jessica
Palmore, Tara N.
Zelzany, Adrian
Adams, Eleanor H.
Quinn, Monica
Chaturvedi, Sudha
Greenko, Jane
Fernandez, Rafael
Southwick, Karen
Furuya, E. Yoko
Calfee, David P.
Hamula, Camille
Patel, Gopi
Barrett, Patricia
Lafaro, Patricia
Berkow, Elizabeth L.
Moulton-Meissner, Heather
Noble-Wang, Judith
Fagan, Ryan P.
Jackson, Brendan R.
Lockhart, Shawn R.
Litvintseva, Anastasia P.
Chiller, Tom M.
TI Investigation of the First Seven Reported Cases of Candida auris, a
Globally Emerging Invasive, Multidrug-Resistant Fungus - United States,
May 2013-August 2016
SO MMWR-MORBIDITY AND MORTALITY WEEKLY REPORT
LA English
DT Article
C1 [Vallabhaneni, Snigdha; Tsay, Sharon; Chow, Nancy; Welsh, Rory; Berkow, Elizabeth L.; Jackson, Brendan R.; Lockhart, Shawn R.; Litvintseva, Anastasia P.; Chiller, Tom M.] CDC, Mycot Dis Branch, Div Food Water & Environm Dis, Atlanta, GA 30333 USA.
[Kallen, Alex; Moulton-Meissner, Heather; Noble-Wang, Judith; Fagan, Ryan P.] CDC, Div Healthcare Qual Promot, Atlanta, GA 30333 USA.
[Tsay, Sharon; Kerins, Janna] CDC, Epidem Intelligence Serv, Ctr Surveillance Epidemiol & Lab Serv, Atlanta, GA 30333 USA.
[Kerins, Janna; Kemble, Sarah K.; Pacilli, Massimo; Black, Stephanie R.] Chicago Dept Publ Hlth, Chicago, IL USA.
[Landon, Emily; Ridgway, Jessica] Univ Chicago, Chicago, IL 60637 USA.
[Palmore, Tara N.; Zelzany, Adrian] NIH, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA.
[Adams, Eleanor H.; Quinn, Monica; Chaturvedi, Sudha; Greenko, Jane; Fernandez, Rafael; Southwick, Karen] New York State Dept Hlth, New York, NY USA.
[Furuya, E. Yoko] Columbia Univ Coll Phys & Surg, 630 W 168th St, New York, NY 10032 USA.
[Calfee, David P.] Weill Cornell Med, New York, NY USA.
[Hamula, Camille; Patel, Gopi] Icahn Sch Med Mt Sinai, Mt Sinai Hlth Syst, New York, NY 10029 USA.
[Barrett, Patricia] New Jersey Dept Hlth, Trenton, NJ USA.
[Lafaro, Patricia] Robert Wood Johnson Univ Hosp, New Brunswick, NJ USA.
RP Vallabhaneni, S (reprint author), CDC, Mycot Dis Branch, Div Food Water & Environm Dis, Atlanta, GA 30333 USA.
EM svallabhaneni@cdc.gov
NR 10
TC 1
Z9 1
U1 2
U2 2
PU CENTERS DISEASE CONTROL
PI ATLANTA
PA 1600 CLIFTON RD, ATLANTA, GA 30333 USA
SN 0149-2195
EI 1545-861X
J9 MMWR-MORBID MORTAL W
JI MMWR-Morb. Mortal. Wkly. Rep.
PD NOV 11
PY 2016
VL 65
IS 44
BP 1234
EP 1237
PG 4
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA EC3XJ
UT WOS:000388060100007
PM 27832049
ER
PT J
AU Smith, JL
Lee, LC
Read, A
Li, QN
Yu, B
Lee, CS
Luo, J
AF Smith, Jordan L.
Lee, Liam C.
Read, Abigail
Li, Qiuning
Yu, Bing
Lee, Chih-Shia
Luo, Ji
TI One-step immortalization of primary human airway epithelial cells
capable of oncogenic transformation
SO CELL AND BIOSCIENCE
LA English
DT Article
ID HUMAN-PAPILLOMAVIRUS TYPE-16; HUMAN TUMOR-CELLS; LUNG ADENOCARCINOMA;
LIFE-SPAN; TELOMERASE ACTIVITY; CANCER GENOME; MECHANISMS;
KERATINOCYTES; SUFFICIENT; SENESCENCE
AB Background: The ability to transform normal human cells into cancer cells with the introduction of defined genetic alterations is a valuable method for understanding the mechanisms of oncogenesis. Easy establishment of immortalized but non-transformed human cells from various tissues would facilitate these genetic analyses.
Results: We report here a simple, one-step immortalization method that involves retroviral vector mediated co-expression of the human telomerase protein and a shRNA targeting the CDKN2A gene locus. We demonstrate that this method could successfully immortalize human small airway epithelial cells while maintaining their chromosomal stability. We further showed that these cells retain p53 activity and can be transformed by the KRAS oncogene.
Conclusions: Our method simplifies the immortalization process and is broadly applicable for establishing immortalized epithelial cell lines from primary human tissues for cancer research.
C1 [Smith, Jordan L.; Lee, Liam C.; Read, Abigail; Li, Qiuning; Yu, Bing; Lee, Chih-Shia; Luo, Ji] NCI, Lab Canc Biol & Genet, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Smith, Jordan L.] Univ Massachusetts, Sch Med, Worcester, MA USA.
[Smith, Jordan L.] Univ Massachusetts, Grad Sch Biomed Sci, Worcester, MA 01605 USA.
[Lee, Liam C.] Univ Cambridge, Grad Program, Cambridge, England.
[Li, Qiuning] ShanghaiTech Univ, Shanghai, Peoples R China.
[Yu, Bing] Janssen R&D Shanghai Discovery Ctr, Shanghai, Peoples R China.
RP Luo, J (reprint author), NCI, Lab Canc Biol & Genet, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM ji.luo@nih.gov
OI Smith , Jordan /0000-0003-0460-0647
FU NCI Intramural Award [ZIA BC 011304]
FX This work was supported by a NCI Intramural Award ZIA BC 011304 to JL.
NR 33
TC 0
Z9 0
U1 1
U2 1
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 2045-3701
J9 CELL BIOSCI
JI Cell Biosci.
PD NOV 11
PY 2016
VL 6
AR 57
DI 10.1186/s13578-016-0122-6
PG 8
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA EB6PO
UT WOS:000387507300001
PM 27891214
ER
PT J
AU Johnson, KA
Lovinger, DM
AF Johnson, Kari A.
Lovinger, David M.
TI Presynaptic G Protein-Coupled Receptors: Gatekeepers of Addiction?
SO FRONTIERS IN CELLULAR NEUROSCIENCE
LA English
DT Review
DE addiction; self-administration; presynaptic; GPCR; dopamine receptor;
CB1 receptor; metabotropic glutamate receptor; allosteric modulator
ID METABOTROPIC GLUTAMATE RECEPTORS; LONG-TERM DEPRESSION; VENTRAL
TEGMENTAL AREA; CONDITIONED PLACE PREFERENCE; CANNABINOID CB1 RECEPTOR;
POSITIVE ALLOSTERIC MODULATOR; NICOTINE-SEEKING BEHAVIOR; MEDIAL
PREFRONTAL CORTEX; DOPAMINE D2 RECEPTORS; MGLUR(2/3) AGONIST LY379268
AB Drug abuse and addiction cause widespread social and public health problems, and the neurobiology underlying drug actions and drug use and abuse is an area of intensive research. Drugs of abuse alter synaptic transmission, and these actions contribute to acute intoxication as well as the chronic effects of abused substances. Transmission at most mammalian synapses involves neurotransmitter activation of two receptor subtypes, ligand-gated ion channels that mediate fast synaptic responses and G protein-coupled receptors (GPCRs) that have slower neuromodulatory actions. The GPCRs represent a large proportion of neurotransmitter receptors involved in almost all facets of nervous system function. In addition, these receptors are targets for many pharmacotherapeutic agents. Drugs of abuse directly or indirectly affect neuromodulation mediated by GPCRs, with important consequences for intoxication, drug taking and responses to prolonged drug exposure, withdrawal and addiction. Among the GPCRs are several subtypes involved in presynaptic inhibition, most of which are coupled to the G(i/o), class of G protein. There is increasing evidence that these presynaptic G(i/o)-coupled GPCRs have important roles in the actions of drugs of abuse, as well as behaviors related to these drugs. This topic will be reviewed, with particular emphasis on receptors for three neurotransmitters, Dopamine (DA; D-1 and D-2 -like receptors), Endocannabinoids (eCBs; CB1 receptors) and glutamate (group II metabotropic glutamate (mGlu) receptors). The focus is on recent evidence from laboratory animal models (and some evidence in humans) implicating these receptors in the acute and chronic effects of numerous abused drugs, as well as in the control of drug seeking and taking. The ability of drugs targeting these receptors to modify drug seeking behavior has raised the possibility of using compounds targeting these receptors for addiction pharmacotherapy. This topic is also discussed, with emphasis on development of mGlu(2) positive allosteric modulators (PAMs).
C1 [Johnson, Kari A.; Lovinger, David M.] NIAAA, Sect Synapt Pharmacolocy, Lab Integrat Neurosci, NIH, Bethesda, MD 20892 USA.
RP Lovinger, DM (reprint author), NIAAA, Sect Synapt Pharmacolocy, Lab Integrat Neurosci, NIH, Bethesda, MD 20892 USA.
EM lovindav@mail.nih.gov
FU Division of Intramural Clinical and Biological Research of the National
Institute on Alcohol Abuse and Alcoholism, National Institutes of Health
[ZIA AA000416]; National Institute of General Medical Sciences
FX This article was supported by funding from the Division of Intramural
Clinical and Biological Research of the National Institute on Alcohol
Abuse and Alcoholism, National Institutes of Health, project number ZIA
AA000416, and a Postdoctoral Research Associate Fellowship from the
National Institute of General Medical Sciences (to KAJ.). We thank Dr.
David Kupferschmidt for comments on the manuscript.
NR 290
TC 0
Z9 0
U1 21
U2 21
PU FRONTIERS MEDIA SA
PI LAUSANNE
PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015,
SWITZERLAND
SN 1662-5102
J9 FRONT CELL NEUROSCI
JI Front. Cell. Neurosci.
PD NOV 11
PY 2016
VL 10
AR 264
DI 10.3339/fncel.2016.00264
PG 22
WC Neurosciences
SC Neurosciences & Neurology
GA EB8AK
UT WOS:000387612900001
PM 27891077
ER
PT J
AU Viboud, C
Epstein, SL
AF Viboud, Cecile
Epstein, Suzanne L.
TI First flu is forever
SO SCIENCE
LA English
DT Editorial Material
ID INFLUENZA VACCINES; INFECTION; IMMUNITY; VIRUS
C1 [Viboud, Cecile] NIH, Fogarty Int Ctr, Bldg 10, Bethesda, MD 20892 USA.
[Epstein, Suzanne L.] US FDA, Ctr Biol Evaluat & Res, Silver Spring, MD 20993 USA.
RP Viboud, C (reprint author), NIH, Fogarty Int Ctr, Bldg 10, Bethesda, MD 20892 USA.
EM viboudc@mail.nih.gov
NR 10
TC 0
Z9 0
U1 14
U2 14
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 0036-8075
EI 1095-9203
J9 SCIENCE
JI Science
PD NOV 11
PY 2016
VL 354
IS 6313
BP 706
EP 707
DI 10.1126/science.aak9816
PG 2
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EB4FS
UT WOS:000387326300018
PM 27846592
ER
PT J
AU Gostic, KM
Ambrose, M
Worobey, M
Lloyd-Smith, JO
AF Gostic, Katelyn M.
Ambrose, Monique
Worobey, Michael
Lloyd-Smith, James O.
TI Potent protection against H5N1 and H7N9 influenza via childhood
hemagglutinin imprinting
SO SCIENCE
LA English
DT Article
ID A VIRUS; INFECTION; HUMANS; AGE; ANTIBODIES; IMMUNITY; A(H7N9); CHINA;
EPIDEMIOLOGY; VACCINATION
AB Two zoonotic influenza A viruses (IAV) of global concern, H5N1 and H7N9, exhibit unexplained differences in age distribution of human cases. Using data from all known human cases of these viruses, we show that an individual's first IAV infection confers lifelong protection against severe disease from novel hemagglutinin (HA) subtypes in the same phylogenetic group. Statistical modeling shows that protective HA imprinting is the crucial explanatory factor, and it provides 75% protection against severe infection and 80% protection against death for both H5N1 and H7N9. Our results enable us to predict age distributions of severe disease for future pandemics and demonstrate that a novel strain's pandemic potential increases yearly when a group-mismatched HA subtype dominates seasonal influenza circulation. These findings open new frontiers for rational pandemic risk assessment.
C1 [Gostic, Katelyn M.; Ambrose, Monique; Lloyd-Smith, James O.] Univ Calif Los Angeles, Dept Ecol & Evolut Biol, Los Angeles, CA 90095 USA.
[Worobey, Michael] Univ Arizona, Dept Ecol & Evolutionary Biol, Tucson, AZ 85721 USA.
[Lloyd-Smith, James O.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
RP Lloyd-Smith, JO (reprint author), Univ Calif Los Angeles, Dept Ecol & Evolut Biol, Los Angeles, CA 90095 USA.; Worobey, M (reprint author), Univ Arizona, Dept Ecol & Evolutionary Biol, Tucson, AZ 85721 USA.; Lloyd-Smith, JO (reprint author), NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
EM worobey@email.arizona.edu; jlloydsmith@ucla.edu
RI Lloyd-Smith, James/K-4080-2012
OI Lloyd-Smith, James/0000-0001-7941-502X
FU National Institute of General Medical Sciences of the National
Institutes of Health [T32GM008185]; National Science Foundation Graduate
Research Fellowship [DGE-1144087]; David and Lucile Packard Foundation;
National Science Foundation [EF-0928690]; Research and Policy for
Infectious Disease Dynamics (RAPIDD) program of the Science and
Technology Directorate, Department of Homeland Security; Fogarty
International Center, National Institutes of Health
FX We thank the Lloyd-Smith lab and the Worobey lab for helpful comments,
C. Viboud for providing insight into historic influenza data, T. Mega
and S. Wu for assistance compiling data, B. Cowling for sharing poultry
exposure data, and P. Horby for sharing Vietnam contact data. K.M.G. is
supported by the National Institute of General Medical Sciences of the
National Institutes of Health (T32GM008185). M.A. is supported by the
National Science Foundation Graduate Research Fellowship (DGE-1144087).
M.W. is supported by the David and Lucile Packard Foundation. J.O.L-S.
is supported by the National Science Foundation (EF-0928690); the
Research and Policy for Infectious Disease Dynamics (RAPIDD) program of
the Science and Technology Directorate, Department of Homeland Security;
and Fogarty International Center, National Institutes of Health. The
content is solely the responsibility of the authors and does not
necessarily represent the official views of the National Institutes of
Health. The authors declare no competing financial interests. Case data
and code for model fitting are available as supplementary data files.
Requests for materials should be addressed to M.W. or J.O.L.-S.
NR 34
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Z9 2
U1 15
U2 15
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 NOV 11
PY 2016
VL 354
IS 6313
BP 722
EP 726
AR aag1322
DI 10.1126/science.aag1322
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EB4FS
UT WOS:000387326300030
PM 27846599
ER
PT J
AU Hu, B
Jin, CC
Li, HB
Tong, JY
Ouyang, XS
Cetinbas, NM
Zhu, S
Strowig, T
Lam, FC
Zhao, C
Henao-Mejia, J
Yilmaz, O
Fitzgerald, KA
Eisenbarth, SC
Elinav, E
Flavell, RA
AF Hu, Bo
Jin, Chengcheng
Li, Hua-Bing
Tong, Jiyu
Ouyang, Xinshou
Cetinbas, Naniye Malli
Zhu, Shu
Strowig, Till
Lam, Fred C.
Zhao, Chen
Henao-Mejia, Jorge
Yilmaz, Omer
Fitzgerald, Katherine A.
Eisenbarth, Stephanie C.
Elinav, Eran
Flavell, Richard A.
TI The DNA-sensing AIM2 inflammasome controls radiation-induced cell death
and tissue injury
SO SCIENCE
LA English
DT Article
ID GASTROINTESTINAL SYNDROME; MEDICAL-MANAGEMENT; SENSOR AIM2; MICE;
APOPTOSIS; P53; ACTIVATION; EXPOSURE
AB Acute exposure to ionizing radiation induces massive cell death and severe damage to tissues containing actively proliferating cells, including bone marrow and the gastrointestinal tract. However, the cellular and molecular mechanisms underlying this pathology remain controversial. Here, we show that mice deficient in the double-stranded DNA sensor AIM2 are protected from both subtotal body irradiation-induced gastrointestinal syndrome and total body irradiation-induced hematopoietic failure. AIM2 mediates the caspase-1-dependent death of intestinal epithelial cells and bone marrow cells in response to double-strand DNA breaks caused by ionizing radiation and chemotherapeutic agents. Mechanistically, we found that AIM2 senses radiation-induced DNA damage in the nucleus to mediate inflammasome activation and cell death. Our results suggest that AIM2 may be a new therapeutic target for ionizing radiation exposure.
C1 [Hu, Bo; Jin, Chengcheng; Li, Hua-Bing; Tong, Jiyu; Zhu, Shu; Strowig, Till; Henao-Mejia, Jorge; Eisenbarth, Stephanie C.; Elinav, Eran; Flavell, Richard A.] Yale Univ, Dept Immunobiol, Sch Med, New Haven, CT 06520 USA.
[Tong, Jiyu] Jinan Univ, Biomed Translat Res Inst, Guangzhou 510632, Guangdong, Peoples R China.
[Ouyang, Xinshou] Yale Univ, Sect Digest Dis, New Haven, CT 06520 USA.
[Cetinbas, Naniye Malli; Lam, Fred C.; Yilmaz, Omer] MIT, Koch Inst Integrat Canc Biol, 500 Main St, Cambridge, MA 02139 USA.
[Zhao, Chen] NIH, Hematol Oncol Fellowship Program, Bldg 10, Bethesda, MD 20892 USA.
[Fitzgerald, Katherine A.] Univ Massachusetts, Sch Med, Program Innate Immun, Div Infect Dis & Immunol, Worcester, MA 01605 USA.
[Eisenbarth, Stephanie C.] Yale Univ, Dept Lab Med, Sch Med, New Haven, CT 06520 USA.
[Flavell, Richard A.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA.
[Strowig, Till] Helmholtz Ctr Infect Res, Inhoffenstr 7, D-38124 Braunschweig, Germany.
[Henao-Mejia, Jorge] Univ Penn, Perelman Sch Med, Inst Immunol, Philadelphia, PA 19104 USA.
[Elinav, Eran] Weizmann Inst Sci, Dept Immunol, Rehovot, Israel.
RP Flavell, RA (reprint author), Yale Univ, Dept Immunobiol, Sch Med, New Haven, CT 06520 USA.; Flavell, RA (reprint author), Howard Hughes Med Inst, Chevy Chase, MD 20815 USA.
EM richard.flavell@yale.edu
OI Strowig, Till/0000-0003-0185-1459; Li, Huabing/0000-0003-3573-6803
FU NIH [T32 2T32DK007356]; Howard Hughes Medical Institute
FX We thank V. M. Dixit, N. Kayagaki, and E. S. Alnemri for sharing
materials and reagents, and V. A. Rathinam for technical advice. We
thank P. Bongiorni for assistance with radiation experiments. The data
presented in this manuscript are tabulated in the main paper and in the
supplementary materials. H.-B.L. is supported by NIH T32 2T32DK007356.
This work was supported by the Howard Hughes Medical Institute (R.A.F.).
NR 24
TC 1
Z9 1
U1 15
U2 15
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 NOV 11
PY 2016
VL 354
IS 6313
BP 765
EP 768
DI 10.1126/science.aaf7532
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EB4FS
UT WOS:000387326300041
PM 27846608
ER
PT J
AU Kitajima, N
Numaga-Tomita, T
Watanabe, M
Kuroda, T
Nishimura, A
Miyano, K
Yasuda, S
Kuwahara, K
Sato, Y
Ide, T
Birnbaumer, L
Sumimoto, H
Mori, Y
Nishida, M
AF Kitajima, Naoyuki
Numaga-Tomita, Takuro
Watanabe, Masahiko
Kuroda, Takuya
Nishimura, Akiyuki
Miyano, Kei
Yasuda, Satoshi
Kuwahara, Koichiro
Sato, Yoji
Ide, Tomomi
Birnbaumer, Lutz
Sumimoto, Hideki
Mori, Yasuo
Nishida, Motohiro
TI TRPC3 positively regulates reactive oxygen species driving maladaptive
cardiac remodeling
SO SCIENTIFIC REPORTS
LA English
DT Article
ID SMALL GTPASE RAC; HEART-FAILURE; NADPH OXIDASES; CA2+ INFLUX; CHANNELS;
ACTIVATION; HYPERTROPHY; SUPEROXIDE; BETA; ANGIOTENSIN
AB Reactive oxygen species (ROS) produced by NADPH oxidase 2 (Nox2) function as key mediators of mechanotransduction during both physiological adaptation to mechanical load and maladaptive remodeling of the heart. This is despite low levels of cardiac Nox2 expression. The mechanism underlying the transition from adaptation to maladaptation remains obscure, however. We demonstrate that transient receptor potential canonical 3 (TRPC3), a Ca2+-permeable channel, acts as a positive regulator of ROS (PRROS) in cardiomyocytes, and specifically regulates pressure overload-induced maladaptive cardiac remodeling in mice. TRPC3 physically interacts with Nox2 at specific C-terminal sites, thereby protecting Nox2 from proteasome-dependent degradation and amplifying Ca2+-dependent Nox2 activation through TRPC3-mediated background Ca2+ entry. Nox2 also stabilizes TRPC3 proteins to enhance TRPC3 channel activity. Expression of TRPC3 C-terminal polypeptide abolished TRPC3-regulated ROS production by disrupting TRPC3-Nox2 interaction, without affecting TRPC3-mediated Ca2+ influx. The novel TRPC3 function as a PRROS provides a mechanistic explanation for how diastolic Ca2+ influx specifically encodes signals to induce ROS-mediated maladaptive remodeling and offers new therapeutic possibilities.
C1 [Kitajima, Naoyuki; Numaga-Tomita, Takuro; Nishimura, Akiyuki; Nishida, Motohiro] Natl Inst Nat Sci, Natl Inst Physiol Sci, Okazaki Inst Integrat Biosci, Div Cardiocirculatory Signaling, Okazaki, Aichi 4448787, Japan.
[Kitajima, Naoyuki; Sato, Yoji; Nishida, Motohiro] Kyushu Univ, Grad Sch Pharmaceut Sci, Dept Translat Pharmaceut Sci, Fukuoka 8128582, Japan.
[Numaga-Tomita, Takuro; Nishimura, Akiyuki; Nishida, Motohiro] Grad Univ Adv Studies, Sch Life Sci, SOKENDAI, Dept Physiol Sci, Okazaki, Aichi 4448787, Japan.
[Watanabe, Masahiko] Hokkaido Univ, Dept Anat, Sch Med, Sapporo, Hokkaido 0608638, Japan.
[Kuroda, Takuya; Yasuda, Satoshi; Sato, Yoji] Natl Inst Hlth Sci, Div Cell Based Therapeut Prod, Setagaya Ku, Tokyo 1588501, Japan.
[Miyano, Kei; Sumimoto, Hideki] Kyoto Univ, Grad Sch Med Sci, Dept Biochem, Fukuoka 8128582, Japan.
[Kuwahara, Koichiro] Kyoto Univ, Grad Sch Med, Dept Cardiovasc Med, Kyoto 6068507, Japan.
[Ide, Tomomi] Kyushu Univ, Grad Sch Med Sci, Dept Cardiovasc Med, Fukuoka 8128582, Japan.
[Birnbaumer, Lutz] NIEHS, Neurosci Lab, NIH, Res Triangle Pk, NC 27709 USA.
[Birnbaumer, Lutz] Catholic Univ Argentina, Inst Biomed Res BIOMED, C1107AFF, Buenos Aires, DF, Argentina.
[Mori, Yasuo] Kyoto Univ, Grad Sch Engn, Dept Synthet Chem & Biol Chem, Kyoto 6158510, Japan.
[Nishida, Motohiro] JST, PRESTO, 4-1-8 Honcho, Kawaguchi, Saitama 3320012, Japan.
RP Nishida, M (reprint author), Natl Inst Nat Sci, Natl Inst Physiol Sci, Okazaki Inst Integrat Biosci, Div Cardiocirculatory Signaling, Okazaki, Aichi 4448787, Japan.; Nishida, M (reprint author), Kyushu Univ, Grad Sch Pharmaceut Sci, Dept Translat Pharmaceut Sci, Fukuoka 8128582, Japan.; Nishida, M (reprint author), Grad Univ Adv Studies, Sch Life Sci, SOKENDAI, Dept Physiol Sci, Okazaki, Aichi 4448787, Japan.; Nishida, M (reprint author), JST, PRESTO, 4-1-8 Honcho, Kawaguchi, Saitama 3320012, Japan.
EM nishida@nips.ac.jp
RI WATANABE, Masahiko/A-4055-2012
FU Comprehensive Brain Science Network (CBSN); Japan Science and Technology
Agency, Precursory Research for Embryonic Science and Technology
Program; Ministry of Education, Culture, Sports, Science, and Technology
of Japan [25293018, 16H05092, 12J05497, 26670144]; Daiko Foundation;
Naito Memorial Foundation; Intramural Research Program of the NIH
[ZO1-ES-101684]
FX TRPC3(-/-) mice and TRPC(1-7) deficient MEFs were kindly
provided from Dr. Lutz Birnbaumer of the NIEHS, Research Triangle Park,
NC, USA. This research was supported by Comprehensive Brain Science
Network (CBSN) for anti-TRPC3 antibody, and funded by grants from the
Japan Science and Technology Agency, Precursory Research for Embryonic
Science and Technology Program (to M.N.); Grants-in-Aid for Scientific
Research (No. 25293018 and No. 16H05092 to M.N.; No. 12J05497 to N.K.,
No. 26670144 to T.N-T.) and Scientific Research on Innovative Areas
(Research in a Proposed Research Area 'Oxygen Biology' to M.N. and
'Living in Space' to T.N-T.) from the Ministry of Education, Culture,
Sports, Science, and Technology of Japan; Daiko Foundation and Naito
Memorial Foundation (to M.N.); and by the Intramural Research Program of
the NIH (Project ZO1-ES-101684 to L.B.).
NR 33
TC 1
Z9 1
U1 2
U2 2
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2045-2322
J9 SCI REP-UK
JI Sci Rep
PD NOV 11
PY 2016
VL 6
AR 37001
DI 10.1038/srep37001
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EB6FE
UT WOS:000387476100001
PM 27833156
ER
PT J
AU Park, JY
Jo, Y
Ko, E
Luckey, MA
Park, YK
Park, SH
Park, JH
Hong, C
AF Park, Joo-Young
Jo, Yuna
Ko, Eunhee
Luckey, Megan A.
Park, Yoo Kyoung
Park, Se-Ho
Park, Jung-Hyun
Hong, Changwan
TI Soluble gamma c cytokine receptor suppresses IL-15 signaling and impairs
iNKT cell development in the thymus
SO SCIENTIFIC REPORTS
LA English
DT Article
ID DOUBLE-POSITIVE THYMOCYTES; FUNCTIONALLY DISTINCT SUBSETS; V-ALPHA-14I
NKT CELLS; REGULATORY T-CELLS; NATURAL-KILLER; TRANSCRIPTION FACTOR;
LINEAGE FATE; TERMINAL MATURATION; HOMEOSTASIS; DIFFERENTIATION
AB The soluble gamma c protein (s gamma c) is a naturally occurring splice isoform of the gamma c cytokine receptor that is produced by activated T cells and inhibits gamma c cytokine signaling. Here we show that s gamma c expression is also highly upregulated in immature CD4(+)CD8(+) thymocytes but then downregulated in mature thymocytes. These results indicate a developmentally controlled mechanism for s gamma c expression and suggest a potential role for s gamma c in regulating T cell development in the thymus. Indeed, s gamma c overexpression resulted in significantly reduced thymocyte numbers and diminished expansion of immature thymocytes, concordant to its role in suppressing signaling by IL-7, a critical gamma c cytokine in early thymopoiesis. Notably, s gamma c overexpression also impaired generation of iNKT cells, resulting in reduced iNKT cell percentages and numbers in the thymus. iNKT cell development requires IL-15, and we found that s gamma c interfered with IL-15 signaling to suppress iNKT cell generation in the thymus. Thus, s gamma c represents a new mechanism to control cytokine availability during T cell development that constrains mature T cell production and specifically iNKT cell generation in the thymus.
C1 [Park, Joo-Young; Luckey, Megan A.; Park, Jung-Hyun] NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA.
[Jo, Yuna; Ko, Eunhee; Hong, Changwan] Pusan Natl Univ, Dept Anat, Sch Med, Yangsan 626870, South Korea.
[Park, Yoo Kyoung] Kyung Hee Univ, Grad Sch East West Med Sci, Dept Med Nutr, Yongin 446701, South Korea.
[Park, Se-Ho] Korea Univ, Sch Life Sci & Biotechnol, Seoul 136701, South Korea.
RP Hong, C (reprint author), Pusan Natl Univ, Dept Anat, Sch Med, Yangsan 626870, South Korea.
EM chong@pusan.ac.kr
RI Park, Jung Hyun /B-5712-2015
OI Park, Jung Hyun /0000-0002-9547-9055
FU Korean Health Technology R&D Project, Ministry of Health & Welfare,
Republic of Korea [HI14C2512]; Intramural Research Program of the NIH,
National Cancer Institute, Center for Cancer Research
FX We thank members of the Hong lab for critical review of this manuscript.
This work was supported by a grant of the Korean Health Technology R&D
Project, Ministry of Health & Welfare, Republic of Korea (HI14C2512),
and by the Intramural Research Program of the NIH, National Cancer
Institute, Center for Cancer Research.
NR 57
TC 1
Z9 1
U1 1
U2 1
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2045-2322
J9 SCI REP-UK
JI Sci Rep
PD NOV 11
PY 2016
VL 6
AR 36962
DI 10.1038/srep36962
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EB7FD
UT WOS:000387550900001
PM 27833166
ER
PT J
AU Harris, LN
Ismaila, N
McShane, LM
Andre, F
AF Harris, Lyndsay N.
Ismaila, Nofisat
McShane, Lisa M.
Andre, Fabrice
TI Providing Balance in ASCO Clinical Practice Guidelines: CYP2D6
Genotyping and Tamoxifen Efficacy Reply
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Letter
ID POSITIVE BREAST-CANCER; LATE-DISTANT RECURRENCE; MOLECULAR GRADE INDEX;
ADJUVANT TAMOXIFEN; TRIAL; POPULATION; BIOMARKERS; SIGNATURE; SURVIVAL;
THERAPY
C1 [Harris, Lyndsay N.; McShane, Lisa M.] NCI, Bethesda, MD 20892 USA.
[Ismaila, Nofisat] Amer Soc Clin Oncol, Alexandria, VA USA.
[Andre, Fabrice] Inst Gustave Roussy, Paris, France.
RP Harris, LN (reprint author), NCI, Bethesda, MD 20892 USA.
NR 25
TC 0
Z9 0
U1 4
U2 4
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD NOV 10
PY 2016
VL 34
IS 32
BP 3946
EP +
DI 10.1200/JCO.2016.68.7020
PG 4
WC Oncology
SC Oncology
GA ED5XO
UT WOS:000388926900024
ER
PT J
AU Cheng, JJ
McCorvy, JD
Giguere, PM
Zhu, H
Kenakin, T
Roth, BL
Kozikowski, AP
AF Cheng, Jianjun
McCorvy, John D.
Giguere, Patrick M.
Zhu, Hu
Kenakin, Terry
Roth, Bryan L.
Kozikowski, Alan P.
TI Design and Discovery of Functionally Selective Serotonin 2C (5-HT2c)
Receptor Agonists
SO JOURNAL OF MEDICINAL CHEMISTRY
LA English
DT Article
ID LIGANDS; IDENTIFICATION; TRANSDUCTION; DISEASE; MODELS; POTENT; AGENTS;
DRUG; 2B
AB On the basis of the structural similarity of our previous 5-HT2c agonists with the melatonin receptor agonist tasimelteon and the putative biological cross-talk between serotonergic and melatonergic systems, a series of new (2,3-dihydro)benzofuran-based compounds were designed and synthesized. The compounds were evaluated for their selectivity toward 5-HT2A, 5-HT2B, and 5HT(2c) receptors in the calcium flux assay with the ultimate goal to generate selective 5-HT2c agonists. Selected compounds were studied for their functional selectivity by comparing their transduction efficiency at the G protein signaling pathway versus beta-arrestin recruitment. The most functionally selective compound (+)-7e produced weak beta-arrestin recruitment and also demonstrated less receptor desensitization compared to serotonin in both calcium flux and phosphoinositide (PI) hydrolysis assays. We report for the first time that selective 5-HT2c agonists possessing weak beta-arrestin recruitment can produce distinct receptor desensitization properties.
C1 [Cheng, Jianjun; Kozikowski, Alan P.] Univ Illinois, Dept Med Chem & Pharmacognosy, Coll Pharm, Drug Discovery Program, Chicago, IL 60612 USA.
[McCorvy, John D.; Giguere, Patrick M.; Zhu, Hu; Roth, Bryan L.] Univ N Carolina, Sch Med, Natl Inst Mental Hlth, Psychoact Drug Screening Program, Chapel Hill, NC 27599 USA.
[Kenakin, Terry] Univ N Carolina, Sch Med, Div Pharmacol, Chapel Hill, NC 27599 USA.
[Kenakin, Terry] Univ N Carolina, Sch Med, Div Chem Biol & Med Chem, Chapel Hill, NC 27599 USA.
[Cheng, Jianjun] ShanghaiTech Univ, iHuman Inst, 99 Haike Rd, Shanghai 201210, Peoples R China.
[Giguere, Patrick M.] Univ Ottawa, Dept Biochem Microbiol & Immunol, Ottawa, ON K1H 8M5, Canada.
[Zhu, Hu] NCATS, Div Preclin Innovat, 9800 Med Ctr Dr, Rockville, MD 20850 USA.
RP Kozikowski, AP (reprint author), Univ Illinois, Dept Med Chem & Pharmacognosy, Coll Pharm, Drug Discovery Program, Chicago, IL 60612 USA.; Roth, BL (reprint author), Univ N Carolina, Sch Med, Natl Inst Mental Hlth, Psychoact Drug Screening Program, Chapel Hill, NC 27599 USA.
EM bryan_roth@med.unc.edu; kozikowa@uic.edu
FU National Institute of Mental Health (NIMH) [R01MH99993]; Psychoactive
Drug Screening Program (PDSP) [HHSN-271-2013-00017-C]
FX Financial support from the National Institute of Mental Health (NIMH)
(Grant R01MH99993) and Psychoactive Drug Screening Program (PDSP,
Contract HHSN-271-2013-00017-C) is gratefully acknowledged.
NR 36
TC 0
Z9 0
U1 11
U2 11
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0022-2623
EI 1520-4804
J9 J MED CHEM
JI J. Med. Chem.
PD NOV 10
PY 2016
VL 59
IS 21
BP 9866
EP 9880
DI 10.1021/acs.jmedchem.6b01194
PG 15
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA EB9SO
UT WOS:000387737600018
PM 27726356
ER
PT J
AU Johnson, TL
Fischer, RJ
Raffel, SJ
Schwan, TG
AF Johnson, Tammi L.
Fischer, Robert J.
Raffel, Sandra J.
Schwan, Tom G.
TI Host associations and genomic diversity of Borrelia hermsii in an
endemic focus of tick-borne relapsing fever in western North America
SO PARASITES & VECTORS
LA English
DT Article
DE Ornithodoros hermsi; Tick-borne zoonosis; Montana; Argasidae
ID LYME-DISEASE RISK; INTERSTATE OUTBREAK; ORNITHODOROS-HERMSI;
SPECIES-DIVERSITY; UNITED-STATES; GRAND-CANYON; CALIFORNIA; SPIROCHETE;
INFECTION; BURGDORFERI
AB Background: An unrecognized focus of tick-borne relapsing fever caused by Borrelia hermsii was identified in 2002 when five people became infected on Wild Horse Island in Flathead Lake, Montana. The terrestrial small mammal community on the island is composed primarily of pine squirrels (Tamiasciurus hudsonicus) and deer mice (Peromyscus maniculatus), neither of which was known as a natural host for the spirochete. Thus a 3-year study was performed to identify small mammals as hosts for B. hermsii.
Methods: Small mammals were captured alive on two island and three mainland sites, blood samples were collected and examined for spirochetes, and serological tests performed to detect anti-B. hermsii antibodies. Ornithodoros hermsi ticks were collected and fed on laboratory mice to assess infection. Genomic DNA samples from spirochetes isolated from infected mammals and ticks were analyzed by multilocus sequence typing.
Results: Eighteen pine squirrels and one deer mouse had detectable spirochetemias when captured, from which 12 isolates of B. hermsii were established. Most pine squirrels were seropositive, and the five species of sciurids combined had a significantly higher prevalence of seropositive animals than did the other six small mammal species captured. The greater diversity of small mammals on the mainland in contrast to the islands demonstrated that other species in addition to pine squirrels were also involved in the maintenance of B. hermsii at Flathead Lake. Ornithodoros hermsi ticks produced an additional 12 isolates of B. hermsii and multilocus sequence typing identified both genomic groups of B. hermsii described previously, and identified a new genomic subdivision. Experimental infections of deer mice with two strains of B. hermsii demonstrated that these animals were susceptible to infection with spirochetes belonging to Genomic Group II but not Genomic Group I.
Conclusions: Pine squirrels are the primary hosts for the maintenance of B. hermsii on the islands in Flathead Lake, however serological evidence showed that numerous additional species are also involved on the mainland. Future studies testing the susceptibility of several small mammal species to infection with different genetic types of B. hermsii will help define their role as hosts in this and other endemic foci.
C1 [Johnson, Tammi L.; Fischer, Robert J.; Raffel, Sandra J.; Schwan, Tom G.] NIAID, Lab Zoonot Pathogens, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA.
[Johnson, Tammi L.] Ctr Dis Control & Prevent, Div Vector Borne Dis, Ft Collins, CO USA.
[Fischer, Robert J.] NIAID, Virol Lab, Rocky Mt Labs, NIH, Hamilton, MT USA.
RP Schwan, TG (reprint author), NIAID, Lab Zoonot Pathogens, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA.
EM tschwan@niaid.nih.gov
FU Montana Ecology of Infectious Diseases Program; National Science
Foundation Integrative Graduate Education and Research Traineeship;
Division of Intramural Research, National Institute of Allergy and
Infectious Diseases, National Institutes of Health
FX This work was supported by the Montana Ecology of Infectious Diseases
Program, National Science Foundation Integrative Graduate Education and
Research Traineeship, and the Division of Intramural Research, National
Institute of Allergy and Infectious Diseases, National Institutes of
Health.
NR 76
TC 0
Z9 0
U1 5
U2 5
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1756-3305
J9 PARASITE VECTOR
JI Parasites Vectors
PD NOV 10
PY 2016
VL 9
AR 575
DI 10.1186/s13071-016-1863-0
PG 17
WC Parasitology
SC Parasitology
GA EC5AL
UT WOS:000388145400001
PM 27832805
ER
PT J
AU Loftfield, E
O'Brien, TR
Pfeiffer, RM
Howell, CD
Horst, R
Prokunina-Olsson, L
Weinstein, SJ
Albanes, D
Morgan, TR
Freedman, ND
AF Loftfield, Erikka
O'Brien, Thomas R.
Pfeiffer, Ruth M.
Howell, Charles D.
Horst, Ron
Prokunina-Olsson, Ludmila
Weinstein, Stephanie J.
Albanes, Demetrius
Morgan, Timothy R.
Freedman, Neal D.
TI Vitamin D Status and Virologic Response to HCV Therapy in the HALT-C and
VIRAHEP-C Trials
SO PLOS ONE
LA English
DT Article
ID CHRONIC HEPATITIS-C; GENOTYPE 1 INFECTION; PEGINTERFERON ALPHA-2A;
ANTIVIRAL THERAPY; 25-HYDROXYVITAMIN D; AMERICAN PATIENTS; VIRUS
THERAPY; RIBAVIRIN; INTERFERON; METAANALYSIS
AB More than 150 million people worldwide are chronically infected with hepatitis C virus (HCV) and face higher risk of cirrhosis and hepatocellular carcinoma. Highly effective HCV treatments have recently been developed; however, they are costly and therefore poorly suited for application in resource-limited settings where HCV burden is high. Pegylated-interferon alpha (PEG-IFN alpha) and ribavirin (RBV) therapy is far less costly, but also less effective. Vitamin D supplementation has been proposed as an inexpensive adjuvant to treatment, however, prior epidemiological evidence on its effectiveness is inconsistent, with little data available among African Americans who naturally have lower vitamin D concentrations. We thus evaluated associations between baseline vitamin D status, measured by circulating 25-hydroxyvitamin D (25(OH)D), which is considered to be the best marker of vitamin D status in humans, and subsequent response to PEG-IFN alpha/RBV therapy in two large clinical trials that together included 1292 patients infected with HCV genotype 1. We used race-stratified logistic regression models to evaluate multivariable-adjusted associations of 25(OH)D with early virologic response (EVR; 2-log10 HCV RNA decline at week 12) and sustained virologic response (SVR). Among African Americans, we saw no associations. Among European Americans, we saw no association with low vitamin D (<= 20 ng/mL) versus sufficient concentrations (20-<30 ng/mL). However, patients with 25(OH) D >= 30 ng/mL were actually less likely to attain EVR (OR = 0.64, 95% CI = 0.43-0.94) than those with sufficient concentrations, with a similar but non-significant association observed for SVR (OR = 0.49, 95% CI = 0.20-1.17).
C1 [Loftfield, Erikka; O'Brien, Thomas R.; Pfeiffer, Ruth M.; Prokunina-Olsson, Ludmila; Weinstein, Stephanie J.; Albanes, Demetrius; Freedman, Neal D.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Howell, Charles D.] Howard Univ, Coll Med, Dept Med, Washington, DC USA.
[Horst, Ron] Heartland Assays, Ames, IA USA.
[Morgan, Timothy R.] VA Long Beach Healthcare Syst, Long Beach, CA USA.
RP Loftfield, E (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
EM erikka.loftfield@nih.gov
FU Intramural Research Program of the National Institutes of Health,
Division of Cancer Epidemiology and Genetics, National Cancer Institute,
National Institutes of Health; Department of Health and Human Services;
Heartland Assays; National Institute of Diabetes and Digestive and
Kidney Diseases
FX This work was supported by the Intramural Research Program of the
National Institutes of Health, Division of Cancer Epidemiology and
Genetics, National Cancer Institute, National Institutes of Health, and
Department of Health and Human Services. Heartland Assays provided
support in the form of salaries for author [RH], but did not have any
additional role in the study design, data collection and analysis,
decision to publish, or preparation of the manuscript. The specific role
of this author is articulated in the 'author contributions' section.;
This work was supported by the Intramural Research Program of the
National Institutes of Health, Division of Cancer Epidemiology and
Genetics, National Cancer Institute, National Institutes of Health,
Department of Health and Human Services. Heartland Assays provided
support in the form of salaries for author [RH], but did not have any
additional role in the study design, data collection and analysis,
decision to publish, or preparation of the manuscript. The specific role
of this author is articulated in the 'author contributions' section. The
VIRAHEP-C and HALT-C studies were conducted, respectively, by the
VIRAHEP-C and HALT-C Investigators and supported by the National
Institute of Diabetes and Digestive and Kidney Diseases. The data and
samples from the VIRAHEP-C and HALT-C studies reported here were
supplied by the National Institute of Diabetes and Digestive and Kidney
Diseases Central Repositories. This manuscript was not prepared in
collaboration with the VIRAHEP-C study group or the HALT-C study group
and does not necessarily reflect the opinions or views of the VIRAHEP-C
Trial and HALT-C Trial, the National Institute of Diabetes and Digestive
and Kidney Diseases Central Repositories or the National Institute of
Diabetes and Digestive and Kidney Diseases.
NR 51
TC 0
Z9 0
U1 1
U2 1
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD NOV 10
PY 2016
VL 11
IS 11
AR 0166036
DI 10.1371/journal.pone.0166036
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EB9ON
UT WOS:000387725000056
ER
PT J
AU Rienstra, M
Geelhoed, B
Yin, XY
Siland, JE
Vermond, RA
Mulder, BA
Van Der Harst, P
Hillege, HL
Benjamin, EJ
Van Gelder, IC
AF Rienstra, Michiel
Geelhoed, Bastiaan
Yin, Xiaoyan
Siland, Joylene E.
Vermond, Rob A.
Mulder, Bart A.
Van Der Harst, Pim
Hillege, Hans L.
Benjamin, Emelia J.
Van Gelder, Isabelle C.
TI Cluster Individuals Based on Phenotype and Determine the Risk for Atrial
Fibrillation in the PREVEND and Framingham Heart Study Populations
SO PLOS ONE
LA English
DT Article
ID ASSOCIATION CONSENSUS CONFERENCE; LATENT CLASS ANALYSIS; PROGNOSIS;
COHORT
AB Background
Risk prediction of atrial fibrillation (AF) is of importance to improve the early diagnosis and treatment of AF. Latent class analysis takes into account the possible existence of classes of individuals each with shared risk factors, and maybe a better method of incorporating the phenotypic heterogeneity underlying AF.
Methods and findings
Two prospective community-based cohort studies from Netherlands and United States were used. Prevention of Renal and Vascular End-stage Disease (PREVEND) study, started in 1997, and the Framingham Heart Study (FHS) Offspring cohort started in 1971, both with 10-years follow-up. The main objective was to determine the risk of AF using a latent class analysis, and compare the discrimination and reclassification performance with traditional regression analysis. Mean age in PREVEND was 49 13 years, 49.8% were men. During follow-up, 250(3%) individuals developed AF. We built a latent class model based on 18 risk factors. A model with 7 distinct classes (ranging from 341 to 1517 individuals) gave the optimum tradeoff between a high statistical model-likelihood and a low number of model parameters. All classes had a specific profile. The incidence of AF varied; class 1 0.0%, class 2 0.3%, class 3 7.5%, class 4 0.2%, class 5 1.3%, class 6 4.2%, class 7 21.7% (p<0.001). The discrimination (C-statistic 0.830 vs. 0.842, delta-C -0.013, p = 0.22) and reclassification (IDI-0.028, p<0.001, NRI-0.090, p = 0.049, and category-less-NRI -0.049, p = 0.495) performance of both models was comparable. The results were successfully replicated in a sample of the FHS study (n = 3162; mean age 58 9 years, 46.3% men).
Conclusions
Latent class analysis to build an AF risk model is feasible. Despite the heterogeneity in number and severity of risk factors between individuals at risk for AF, latent class analysis produces distinguishable groups.
C1 [Rienstra, Michiel; Geelhoed, Bastiaan; Siland, Joylene E.; Vermond, Rob A.; Mulder, Bart A.; Van Der Harst, Pim; Hillege, Hans L.; Van Gelder, Isabelle C.] Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, Groningen, Netherlands.
[Yin, Xiaoyan; Benjamin, Emelia J.] NHLBI, Framingham, MA USA.
[Yin, Xiaoyan; Benjamin, Emelia J.] Boston Univ, Framingham Heart Study, Framingham, MA USA.
[Benjamin, Emelia J.] Boston Univ, Sch Med, Dept Med, Sect Cardiovasc Med, Boston, MA 02118 USA.
[Benjamin, Emelia J.] Boston Univ, Sch Med, Dept Med, Sect Prevent Med, Boston, MA 02118 USA.
[Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.
RP Rienstra, M (reprint author), Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, Groningen, Netherlands.
EM m.rienstra@umcg.nl
OI Benjamin, Emelia/0000-0003-4076-2336; Rienstra,
Michiel/0000-0002-2581-070X
FU Dutch Kidney Foundation [E0.13]; Netherlands Heart Foundation
[NHS2010B280]; Netherlands Organization for Scientific Research (Veni)
[016.136.055]; EHRA Academic Fellowship program; [HHSN268201500001I];
[N01-HC 25195]; [2R01HL092577]; [1R01HL128914]
FX The PREVEND study is supported by the Dutch Kidney Foundation (grant
E0.13) and the Netherlands Heart Foundation (grant NHS2010B280). Dr. M.
Rienstra is supported by grants from the Netherlands Organization for
Scientific Research (Veni grant 016.136.055) and from the EHRA Academic
Fellowship program. The FHS is supported by HHSN268201500001I, N01-HC
25195, 2R01HL092577, and 1R01HL128914. The funders had no role in study
design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 26
TC 0
Z9 0
U1 1
U2 1
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD NOV 10
PY 2016
VL 11
IS 11
AR e0165828
DI 10.1371/journal.pone.0165828
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EB9ON
UT WOS:000387725000036
PM 27832125
ER
PT J
AU Manson, JE
Brannon, PM
Rosen, CJ
Taylor, CL
AF Manson, JoAnn E.
Brannon, Patsy M.
Rosen, Clifford J.
Taylor, Christine L.
TI Vitamin D Deficiency - Is There Really a Pandemic?
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Editorial Material
ID EUROPE
C1 [Manson, JoAnn E.] Brigham & Womens Hosp, Dept Med, 75 Francis St, Boston, MA 02115 USA.
[Manson, JoAnn E.] Harvard Med Sch, Boston, MA 02115 USA.
[Brannon, Patsy M.] Cornell Univ, Div Nutr Sci, Ithaca, NY 14853 USA.
[Rosen, Clifford J.] Maine Med Ctr Res Inst, Ctr Clin & Translat Med, Scarborough, ME USA.
[Taylor, Christine L.] NIH, Off Dietary Supplements, Bldg 10, Bethesda, MD 20892 USA.
RP Manson, JE (reprint author), Brigham & Womens Hosp, Dept Med, 75 Francis St, Boston, MA 02115 USA.; Manson, JE (reprint author), Harvard Med Sch, Boston, MA 02115 USA.
FU NCI NIH HHS [R01 CA138962]
NR 5
TC 2
Z9 2
U1 4
U2 4
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 NOV 10
PY 2016
VL 375
IS 19
BP 1817
EP 1820
DI 10.1056/NEJMp1608005
PG 4
WC Medicine, General & Internal
SC General & Internal Medicine
GA EB6ZK
UT WOS:000387534200004
PM 27959647
ER
PT J
AU Shehata, MA
Nohr, AC
Lissa, D
Bisig, C
Isberg, V
Andersen, KB
Harpsoe, K
Bjorkling, F
Brauner-Osborne, H
Gloriam, DE
AF Shehata, Mohamed A.
Nohr, Anne C.
Lissa, Delphine
Bisig, Christoph
Isberg, Vignir
Andersen, Kirsten B.
Harpsoe, Kasper
Bjorkling, Fredrik
Brauner-Osborne, Hans
Gloriam, David E.
TI Novel Agonist Bioisosteres and Common Structure-Activity Relationships
for The Orphan G Protein-Coupled Receptor GPR139
SO SCIENTIFIC REPORTS
LA English
DT Article
ID FINGERPRINTS; LIGANDS; TARGETS
AB GPR139 is an orphan class A G protein-coupled receptor found mainly in the central nervous system. It has its highest expression levels in the hypothalamus and striatum, regions regulating metabolism and locomotion, respectively, and has therefore been suggested as a potential target for obesity and Parkinson's disease. The two aromatic amino acids (L)-Trp and (L)-Phe have been proposed as putative endogenous agonists, and three structurally related benzohydrazide, glycine benzamide, and benzotriazine surrogate agonist series have been published. Herein, we assayed 158 new analogues selected from a pharmacophore model, and identified 12 new GPR139 agonists, containing previously untested bioisosteres. Furthermore, we present the first combined structure-activity relationships, and a refined pharmacophore model to serve as a rationale for future ligand identification and optimization.
C1 [Shehata, Mohamed A.; Nohr, Anne C.; Lissa, Delphine; Bisig, Christoph; Isberg, Vignir; Andersen, Kirsten B.; Harpsoe, Kasper; Bjorkling, Fredrik; Brauner-Osborne, Hans; Gloriam, David E.] Univ Copenhagen, Fac Hlth & Med Sci, Dept Drug Design & Pharmacol, Univ Pk 2, DK-2100 Copenhagen, Denmark.
[Andersen, Kirsten B.] H Lundbeck & Co AS, Dept Neurodegenerat 1, Ottiliavej 9, DK-2500 Valby, Denmark.
[Lissa, Delphine] NCI, Human Carcinogenesis Lab, NIH, Bldg 37, Bethesda, MD 20892 USA.
[Bisig, Christoph] Univ Fribourg, Adolphe Merkle Inst, Chemin Verdiers 4, CH-1700 Fribourg, Switzerland.
[Isberg, Vignir] Novozymes AS, Krogshojvej 36, DK-2880 Bagsvaerd, Denmark.
[Andersen, Kirsten B.] Danish Vet & Food Adm, Minist Environm & Food Denmark, Stn Pk 31-33, DK-2600 Glostrup, Denmark.
RP Brauner-Osborne, H; Gloriam, DE (reprint author), Univ Copenhagen, Fac Hlth & Med Sci, Dept Drug Design & Pharmacol, Univ Pk 2, DK-2100 Copenhagen, Denmark.
EM hbo@sund.ku.dk; david.gloriam@sund.ku.dk
OI Shehata, Mohamed/0000-0001-5475-1967; Brauner-Osborne,
Hans/0000-0001-9495-7388; Gloriam, David/0000-0002-4299-7561; Harpsoe,
Kasper/0000-0002-9326-9644
FU Lundbeck Foundation [R163-2013-16327]; Danish Council for Independent
Research (DFF) [1331-00180]; European Research Council [DE-ORPHAN
639125]; A. P. Moller Foundation for the Advancement of Medical
Sciences; Lundbeck Foundation; Faculty of Health and Medical Sciences
FX This work was supported by grants from the Lundbeck Foundation
(R163-2013-16327 to D.E.G.), The Danish Council for Independent Research
(DFF - 1331-00180 to D.E.G.) and European Research Council (DE-ORPHAN
639125 to D.E.G.); and the A. P. Moller Foundation for the Advancement
of Medical Sciences and the Lundbeck Foundation (H.B.-O.). M.A.S. and
A.C.N. acknowledge funding from the Faculty of Health and Medical
Sciences.
NR 30
TC 1
Z9 1
U1 3
U2 3
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2045-2322
J9 SCI REP-UK
JI Sci Rep
PD NOV 10
PY 2016
VL 6
AR 36681
DI 10.1038/srep36681
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EB6QX
UT WOS:000387510900001
PM 27830715
ER
PT J
AU Xu, H
Li, ZY
Yu, Y
Sizdahkhani, S
Ho, WS
Yin, FC
Wang, L
Zhu, GL
Zhang, M
Jiang, L
Zhuang, ZP
Qin, JH
AF Xu, Hui
Li, Zhongyu
Yu, Yue
Sizdahkhani, Saman
Ho, Winson S.
Yin, Fangchao
Wang, Li
Zhu, Guoli
Zhang, Min
Jiang, Lei
Zhuang, Zhengping
Qin, Jianhua
TI A dynamic in vivo-like organotypic blood-brain barrier model to probe
metastatic brain tumors
SO SCIENTIFIC REPORTS
LA English
DT Article
ID MICROVASCULAR ENDOTHELIAL-CELLS; VITRO MODEL; ELECTRICAL-RESISTANCE;
BBB; CANCER; CHIP; RAT; PERMEABILITY; EXPRESSION; SYSTEM
AB The blood-brain barrier (BBB) restricts the uptake of many neuro-therapeutic molecules, presenting a formidable hurdle to drug development in brain diseases. We proposed a new and dynamic in vivo-like three-dimensional microfluidic system that replicates the key structural, functional and mechanical properties of the blood-brain barrier in vivo. Multiple factors in this system work synergistically to accentuate BBB-specific attributes-permitting the analysis of complex organ-level responses in both normal and pathological microenvironments in brain tumors. The complex BBB microenvironment is reproduced in this system via physical cell-cell interaction, vascular mechanical cues and cell migration. This model possesses the unique capability to examine brain metastasis of human lung, breast and melanoma cells and their therapeutic responses to chemotherapy. The results suggest that the interactions between cancer cells and astrocytes in BBB microenvironment might affect the ability of malignant brain tumors to traverse between brain and vascular compartments. Furthermore, quantification of spatially resolved barrier functions exists within a single assay, providing a versatile and valuable platform for pharmaceutical development, drug testing and neuroscientific research.
C1 [Xu, Hui; Li, Zhongyu; Yu, Yue; Yin, Fangchao; Wang, Li; Zhu, Guoli; Zhang, Min; Jiang, Lei; Qin, Jianhua] Chinese Acad Sci, Dalian Inst Chem Phys, Div Biotechnol, Dalian, Peoples R China.
[Xu, Hui; Li, Zhongyu; Yu, Yue; Yin, Fangchao; Zhu, Guoli] Univ Chinese Acad Sci, Beijing, Peoples R China.
[Sizdahkhani, Saman; Ho, Winson S.; Zhuang, Zhengping] NINDS, Surg Neurol Branch, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
RP Qin, JH (reprint author), Chinese Acad Sci, Dalian Inst Chem Phys, Div Biotechnol, Dalian, Peoples R China.
EM jhqin@dicp.ac.cn
OI Yu, Yue/0000-0003-0633-9577
FU National Nature Science Foundation of China [91543121, 31671038,
81573394, 81273483]; International Science & Technology Cooperation
Program of China [2015DFA00740]; Key Laboratory of Separation Science
for Analytical Chemistry (Dalian Institute of Chemical Physics, Chinese
Academy of Sciences)
FX This research was supported by National Nature Science Foundation of
China (Nos 91543121, 31671038, 81573394, 81273483), International
Science & Technology Cooperation Program of China (2015DFA00740), Key
Laboratory of Separation Science for Analytical Chemistry (Dalian
Institute of Chemical Physics, Chinese Academy of Sciences).
NR 48
TC 0
Z9 0
U1 20
U2 20
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 NOV 10
PY 2016
VL 6
AR 36670
DI 10.1038/srep36670
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EB6QW
UT WOS:000387510800001
PM 27830712
ER
PT J
AU Baker, PM
Jhou, T
Li, B
Matsumoto, M
Mizumori, SJY
Stephenson-Jones, M
Vicentic, A
AF Baker, Phillip M.
Jhou, Thomas
Li, Bo
Matsumoto, Masayuki
Mizumori, Sheri J. Y.
Stephenson-Jones, Marcus
Vicentic, Aleksandra
TI The Lateral Habenula Circuitry: Reward Processing and Cognitive Control
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
DE anterior cingulate cortex; cognition; globus pallidus; lateral habenula;
punishment; reward; rostromedial tegmental nucleus
ID VENTRAL TEGMENTAL AREA; ANTERIOR CINGULATE CORTEX; MIDBRAIN DOPAMINE
NEURONS; NEGATIVE MOTIVATIONAL VALUE; OPPONENT-PROCESS THEORY; BASAL
GANGLIA; NONHUMAN-PRIMATES; SUBSTANTIA-NIGRA; DECISION-MAKING;
MOTOR-RESPONSES
AB There has been a growing interest in understanding the role of the lateral habenula (LHb) in reward processing, affect regulation, and goal-directed behaviors. The LHb gets major inputs from the habenula-projecting globus pallidus and the mPFC, sending its efferents to the dopaminergic VTA and SNc, serotonergic dorsal raphe nuclei, and the GABAergic rostromedial tegmental nucleus. Recent studies have made advances in our understanding of the LHb circuit organization, yet the precise mechanisms of its involvement in complex behaviors are largely unknown. To begin to address this unresolved question, we present here emerging cross-species perspectives with a goal to provide a more refined understanding of the role of the LHb circuits in reward and cognition. We begin by highlighting recent findings from rodent experiments using optogenetics, electrophysiology, molecular, pharmacology, and tracing techniques that reveal diverse neural phenotypes in the LHb circuits that may underlie previously undescribed behavioral functions. We then discuss results from electrophysiological studies in macaques that suggest that the LHb cooperates with the anterior cingulate cortex to monitor action outcomes and signal behavioral adjustment. Finally, weprovide an integrated summary of cross-species findings and discuss how further research on the connectivity, neural signaling, and physiology of the LHb circuits can deepen our understanding of the role of the LHb in normal and maladaptive behaviors associated with mental illnesses and drug abuse.
C1 [Baker, Phillip M.; Mizumori, Sheri J. Y.] Univ Washington, Dept Psychol, Seattle, WA 98195 USA.
[Jhou, Thomas] Med Univ South Carolina, Dept Neurosci, Charleston, SC 29425 USA.
[Li, Bo; Stephenson-Jones, Marcus] Cold Spring Harbor Lab, POB 100, Cold Spring Harbor, NY 11724 USA.
[Matsumoto, Masayuki] Univ Tsukuba, Div Biomed Sci, Fac Med, Ibaraki 3058577, Japan.
[Vicentic, Aleksandra] NIMH, Div Neurosci & Basic Behav Sci, Bethesda, MD 20892 USA.
RP Li, B (reprint author), Cold Spring Harbor Lab, POB 100, Cold Spring Harbor, NY 11724 USA.; Vicentic, A (reprint author), NIMH, Div Neurosci & Basic Behav Sci, Bethesda, MD 20892 USA.
EM bli@cshl.edu; vicentica@mail.nih.gov
OI Baker, Phillip/0000-0002-3023-2983
FU National Institute of Drug Abuse Grant [T32 DA07278 - 20]; National
Institute of Mental Health [R01MH108924, R01MH58755]; National Institute
of Drug Abuse [1R01DA037327]; National Institute on Drug Abuse
[1R21DA032898]; Cabinet Office, Government of Japan Funding Program for
Next Generation World-Leading Researchers [LS074]; Ministry of
Education, Culture, Sports, Science and Technology of Japan [26120707];
Takeda Science Foundation; Inamori Foundation; Uehara Memorial
Foundation; University of Washington Research Royalty Fund Grant;
National Alliance for Research on Schizophrenia and Depression; EMBO
Long-Term Fellowship Awards
FX This work was supported by National Institute of Drug Abuse Grant T32
DA07278 - 20 to P.M.B., National Institute of Mental Health Grant
R01MH108924 to B.L., National Institute of Drug Abuse Grants
1R01DA037327 and National Institute on Drug Abuse 1R21DA032898 to T.J.,
Cabinet Office, Government of Japan Funding Program for Next Generation
World-Leading Researchers LS074, Ministry of Education, Culture, Sports,
Science and Technology of Japan Grants-in-Aid for Scientific Research
26120707, Takeda Science Foundation, Inamori Foundation, and Uehara
Memorial Foundation to M.M., National Institute of Mental Health Grant
R01MH58755 and University of Washington Research Royalty Fund Grant to
S.J.Y.M., and National Alliance for Research on Schizophrenia and
Depression and EMBO Long-Term Fellowship Awards to M.S.-J.
NR 72
TC 0
Z9 0
U1 7
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 NOV 9
PY 2016
VL 36
IS 45
BP 11482
EP 11488
DI 10.1523/JNEUROSCI.2350-16.2016
PG 7
WC Neurosciences
SC Neurosciences & Neurology
GA EG5AC
UT WOS:000391054300013
PM 27911751
ER
PT J
AU Aron, AR
Herz, DM
Brown, P
Forstmann, BU
Zaghloul, K
AF Aron, Adam R.
Herz, Damian M.
Brown, Peter
Forstmann, Birte U.
Zaghloul, Kareem
TI Frontosubthalamic Circuits for Control of Action and Cognition
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
DE basal ganglia; conflict; oscillations; response inhibition; stopping;
surprise
ID TRANSCRANIAL MAGNETIC STIMULATION; HUMAN SUBTHALAMIC NUCLEUS;
SUPPLEMENTARY MOTOR AREA; DEEP BRAIN-STIMULATION; CORTICOSUBTHALAMIC
INPUT ZONES; SIGNAL RESPONSE-INHIBITION; INFERIOR FRONTAL GYRUS;
BASAL-GANGLIA; PARKINSONS-DISEASE; FUNCTIONAL-ANATOMY
AB The subthalamic nucleus (STN) of the basal ganglia appears to have a potent role in action and cognition. Anatomical and imaging studies show that different frontal cortical areas directly project to the STN via so-called hyperdirect pathways. This review reports some of the latest findings about such circuits, including simultaneous recordings from cortex and the STN in humans, single-unit recordings in humans, high-resolution fMRI, and neurocomputational modeling. We argue that a major function of the STN is to broadly pause behavior and cognition when stop signals, conflict signals, or surprise signals occur, and that the fronto-STN circuits for doing this, at least for stopping and conflict, are dissociable anatomically and in terms of their spectral reactivity. Wealso highlight recent evidence for synchronization of oscillations between prefrontal cortex and the STN, which may provide a preferential "window in time" for single neuron communication via long-range connections.
C1 [Aron, Adam R.] Univ Calif San Diego, Dept Psychol, San Diego, CA 92093 USA.
[Herz, Damian M.; Brown, Peter] Univ Oxford, MRC, Brain Network Dynam Unit, Oxford OX1 3TH, England.
[Herz, Damian M.; Brown, Peter] Univ Oxford, Nuffield Dept Clin Neurosci, Oxford OX1 3TH, England.
[Forstmann, Birte U.] Univ Amsterdam, Amsterdam Brain & Cognit Ctr, Psychol, Roetersstr 15, NL-1018 Amsterdam, Netherlands.
[Zaghloul, Kareem] Natl Inst Neurol Disorders & Stroke, NIH, Bethesda, MD 20892 USA.
RP Aron, AR (reprint author), Univ Calif San Diego, Dept Psychol, 9500 Gilman Dr, La Jolla, CA 92093 USA.
EM adamaron@ucsd.edu
OI Brown, Peter/0000-0002-5201-3044
FU National Institutes of Health [DA DA026452]; James S. McDonnell Grant
[220020375]; European Union [655605]; Medical Research Council of Great
Britain [MC_UU_12024/1]; European Research Council; Netherlands
Organization for Scientific Research
FX A.R.A. was supported by National Institutes of Health DA DA026452 and
James S. McDonnell Grant 220020375. D.M.H. was supported by European
Union's Horizon 2020 research and innovation program under the Marie
Sklodowska-Curie Grant Agreement 655605. P.B. was supported by Medical
Research Council of Great Britain MC_UU_12024/1. B.U.F. was supported by
the European Research Council and Netherlands Organization for
Scientific Research. We thank Nader Pouratian for discussion, Navarre
Guiterrez-Read for assistance with the figure, and Johanna Wagner and
Eleonora Bartoli for comments on the manuscript.
NR 98
TC 1
Z9 1
U1 12
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 NOV 9
PY 2016
VL 36
IS 45
BP 11489
EP 11495
DI 10.1523/JNEUROSCI.2348-16.2016
PG 7
WC Neurosciences
SC Neurosciences & Neurology
GA EG5AC
UT WOS:000391054300014
PM 27911752
ER
PT J
AU Ji, B
Kaneko, H
Minamimoto, T
Inoue, H
Takeuchi, H
Kumata, K
Zhang, MR
Aoki, I
Seki, C
Ono, M
Tokunaga, M
Tsukamoto, S
Tanabe, K
Shin, RM
Minamihisamatsu, T
Kito, S
Richmond, BJ
Suhara, T
Higuchi, M
AF Ji, Bin
Kaneko, Hiroyuki
Minamimoto, Takafumi
Inoue, Haruhisa
Takeuchi, Hiroki
Kumata, Katsushi
Zhang, Ming-Rong
Aoki, Ichio
Seki, Chie
Ono, Maiko
Tokunaga, Masaki
Tsukamoto, Satoshi
Tanabe, Koji
Shin, Ryong-Moon
Minamihisamatsu, Takeharu
Kito, Seiji
Richmond, Barry J.
Suhara, Tetsuya
Higuchi, Makoto
TI Multimodal Imaging for DREADD-Expressing Neurons in Living Brain and
Their Application to Implantation of iPSC-Derived Neural Progenitors
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
DE cell replacement therapy; clozapine-N-oxide (CNO); designer receptor
exclusively activated by designer drugs (DREADD); induced pluripotent
stem cell (iPSC); positron emission tomography (PET)
ID SPINAL-CORD-INJURY; PLURIPOTENT STEM-CELLS; PROTEIN-COUPLED RECEPTORS;
CENTRAL-NERVOUS-SYSTEM; CLOZAPINE-N-OXIDE; PARKINSONS-DISEASE; MOUSE
MODEL; IN-VIVO; CANNABINOID RECEPTORS; MUSCARINIC RECEPTORS
AB Chemogenetic manipulation of neuronal activities has been enabled by a designer receptor (designer receptor exclusively activated by designer drugs, DREADD) that is activated exclusively by clozapine-N-oxide (CNO). Here, we applied CNO as a functional reporter probe to positron emission tomography (PET) of DREADD in living brains. Mutant human M4 DREADD (hM4Di) expressed in transgenic (Tg) mouse neurons was visualized by PET with microdose [C-11] CNO. Deactivation of DREADD-expressing neurons in these mice by nonradioactive CNO at a pharmacological dose could also be captured by arterial spin labeling MRI (ASL-MRI). Neural progenitors derived from hM4Di Tg-induced pluripotent stem cells were then implanted into WT mouse brains and neuronal differentiation of the grafts could be imaged by [C-11] CNO-PET. Finally, ASL-MRI captured chemogenetic functional manipulation of the graft neurons. Our data provide the first demonstration of multimodal molecular/functional imaging of cells expressing a functional gene reporter in the brain, which would be translatable to humans for therapeutic gene transfers and cell replacements.
C1 [Ji, Bin; Kaneko, Hiroyuki; Minamimoto, Takafumi; Seki, Chie; Ono, Maiko; Tokunaga, Masaki; Shin, Ryong-Moon; Minamihisamatsu, Takeharu; Suhara, Tetsuya; Higuchi, Makoto] Natl Inst Quantum & Radiol Sci & Technol, Dept Funct Brain Imaging Res, Chiba 2638555, Japan.
[Kumata, Katsushi; Zhang, Ming-Rong] Natl Inst Quantum & Radiol Sci & Technol, Dept Radiopharmaceut Dev, Chiba 2638555, Japan.
[Aoki, Ichio] Natl Inst Quantum & Radiol Sci & Technol, Dept Mol Imaging & Theranost, Chiba 2638555, Japan.
[Tsukamoto, Satoshi; Kito, Seiji] Natl Inst Quantum & Radiol Sci & Technol, Natl Inst Radiol Sci, Lab Anim & Genome Sci Sect, Chiba 2638555, Japan.
[Inoue, Haruhisa; Takeuchi, Hiroki; Tanabe, Koji] Kyoto Univ, Ctr iPS Cell Res & Applicat CiRA, Kyoto, Kyoto 6068507, Japan.
[Richmond, Barry J.] NIMH, Neuropsychol Lab, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Ji, Bin; Inoue, Haruhisa; Suhara, Tetsuya; Higuchi, Makoto] Japan Sci & Technol Agcy JST, CREST, Kawaguchi, Saitama 3320012, Japan.
RP Higuchi, M (reprint author), Natl Inst Radiol Sci, Mol Imaging Ctr, Inage Ku, 4-9-1 Anagawa, Chiba 2638555, Japan.
EM mhiguchi@nirs.go.jp
OI Aoki, Ichio/0000-0002-4429-5053; Ji, BIn/0000-0002-9672-6441;
Minamimoto, Takafumi/0000-0003-4305-0174
FU Ministry of Education, Culture, Sports, Science and Technology, Japan
[23111009]; Japan Agency for Medical Research and Development
[14533254]; JST Yamanaka iPS Cell Special Project; CREST
FX This work was supported by Grants-in-Aid for the Japan Advanced
Molecular Imaging Program and Scientific Research on Innovative Areas
from the Ministry of Education, Culture, Sports, Science and Technology,
Japan ("Brain Environment" 23111009 to M.H.), for Brain Mapping by
Integrated Neurotechnologies for Disease Studies from the Japan Agency
for Medical Research and Development (Grant 14533254 to M.H.), the JST
Yamanaka iPS Cell Special Project (H.I.), and CREST (H.I. and T.S.).
NR 52
TC 0
Z9 0
U1 1
U2 1
PU SOC NEUROSCIENCE
PI WASHINGTON
PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA
SN 0270-6474
J9 J NEUROSCI
JI J. Neurosci.
PD NOV 9
PY 2016
VL 36
IS 45
BP 11544
EP 11558
DI 10.1523/JNEUROSCI.1279-16.2016
PG 15
WC Neurosciences
SC Neurosciences & Neurology
GA EG5AC
UT WOS:000391054300020
PM 27911758
ER
PT J
AU Saxena, P
He, L
Malyutin, A
Datta, SAK
Rein, A
Bond, KM
Jarrold, MF
Spilotros, A
Svergun, D
Douglas, T
Dragnea, B
AF Saxena, Pooja
He, Li
Malyutin, Andrey
Datta, Siddhartha A. K.
Rein, Alan
Bond, Kevin M.
Jarrold, Martin F.
Spilotros, Alessandro
Svergun, Dmitri
Douglas, Trevor
Dragnea, Bogdan
TI Virus Matryoshka: A Bacteriophage Particle-Guided Molecular Assembly
Approach to a Monodisperse Model of the Immature Human Immunodeficiency
Virus
SO SMALL
LA English
DT Article
ID DETECTION MASS-SPECTROMETRY; IN-VITRO; CRYOELECTRON MICROSCOPY; GAG
PROTEIN; SPHERICAL CRYSTALLOGRAPHY; BIOLOGICAL MACROMOLECULES;
RETROVIRUS PARTICLES; HIV-1 MORPHOGENESIS; ANGSTROM RESOLUTION; SOLUTION
SCATTERING
AB Immature human immunodeficiency virus type 1 (HIV-1) is approximately spherical, but is constructed from a hexagonal lattice of the Gag protein. As a hexagonal lattice is necessarily flat, the local symmetry cannot be maintained throughout the structure. This geometrical frustration presumably results in bending stress. In natural particles, the stress is relieved by incorporation of packing defects, but the magnitude of this stress and its significance for the particles is not known. In order to control this stress, we have now assembled the Gag protein on a quasi-spherical template derived from bacteriophage P22. This template is monodisperse in size and electron-transparent, enabling the use of cryo-electron microscopy in structural studies. These templated assemblies are far less polydisperse than any previously described virus-like particles (and, while constructed according to the same lattice as natural particles, contain almost no packing defects). This system gives us the ability to study the relationship between packing defects, curvature and elastic energy, and thermodynamic stability. As Gag is bound to the P22 template by single-stranded DNA, treatment of the particles with DNase enabled us to determine the intrinsic radius of curvature of a Gag lattice, unconstrained by DNA or a template. We found that this intrinsic radius is far larger than that of a virion or P22-templated particle. We conclude that Gag is under elastic strain in a particle; this has important implications for the kinetics of shell growth, the stability of the shell, and the type of defects it will assume as it grows.
C1 [Saxena, Pooja; Malyutin, Andrey; Bond, Kevin M.; Jarrold, Martin F.; Douglas, Trevor; Dragnea, Bogdan] Indiana Univ, Dept Chem, 800 E Kirkwood Ave, Bloomington, IN 47405 USA.
[He, Li] Indiana Univ, Dept Mol & Cellular Biochem, Bloomington, IN 47405 USA.
[Datta, Siddhartha A. K.; Rein, Alan] NCI, POB B,Bldg 535, Frederick, MD 21702 USA.
[Spilotros, Alessandro; Svergun, Dmitri] European Mol Biol Lab DESY, Notkestr 85,Geb 25a, D-22603 Hamburg, Germany.
RP Dragnea, B (reprint author), Indiana Univ, Dept Chem, 800 E Kirkwood Ave, Bloomington, IN 47405 USA.
EM dragnea@indiana.edu
RI Douglas, Trevor/F-2748-2011
FU Human Frontier Science Program [RGP0017/2012]; Intramural Research
Program of the NIH, National Cancer Institute, Center for Cancer
Research; U.S. Department of Energy, Office of Science, Basic Energy
Sciences [DE-SC0010507]
FX P.S. and L.H. contributed equally to this work. The authors gratefully
acknowledge Dr. John A. G. Briggs (European Molecular Biology
Laboratory, Heidelberg, Germany) and Dr. Peter E. Prevelige Jr.
(Department of Microbiology, University of Alabama, Birmingham, USA) for
insightful discussions on this project. The IU Nanoscale
Characterization Facility is thanked for access to instrumentation. This
work was supported by the Human Frontier Science Program research grant
RGP0017/2012 (to B.D., A.R., D.S., and Dr. Paul van der Schoot,
Technische Universiteit Eindhoven, The Netherlands) for work on cryo-EM,
SAXS, molecular biology and numerical simulations; by the Intramural
Research Program of the NIH, National Cancer Institute, Center for
Cancer Research (to A.R.); and by the U.S. Department of Energy, Office
of Science, Basic Energy Sciences, under award DE-SC0010507 (to B.D.)
for work on data processing algorithms.
NR 69
TC 0
Z9 0
U1 7
U2 7
PU WILEY-V C H VERLAG GMBH
PI WEINHEIM
PA POSTFACH 101161, 69451 WEINHEIM, GERMANY
SN 1613-6810
EI 1613-6829
J9 SMALL
JI Small
PD NOV 9
PY 2016
VL 12
IS 42
BP 5862
EP 5872
DI 10.1002/smll.201601712
PG 11
WC Chemistry, Multidisciplinary; Chemistry, Physical; Nanoscience &
Nanotechnology; Materials Science, Multidisciplinary; Physics, Applied;
Physics, Condensed Matter
SC Chemistry; Science & Technology - Other Topics; Materials Science;
Physics
GA EE2HF
UT WOS:000389403900008
ER
PT J
AU Sun, W
Weingarten, RA
Xu, M
Southall, N
Dai, S
Shinn, P
Sanderson, PE
Williamson, PR
Frank, KM
Zheng, W
AF Sun, Wei
Weingarten, Rebecca A.
Xu, Miao
Southall, Noel
Dai, Sheng
Shinn, Paul
Sanderson, Philip E.
Williamson, Peter R.
Frank, Karen M.
Zheng, Wei
TI Rapid antimicrobial susceptibility test for identification of new
therapeutics and drug combinations against multidrug-resistant bacteria
SO EMERGING MICROBES & INFECTIONS
LA English
DT Article
DE antimicrobial susceptibility testing; drug repositioning; drug
repurposing; Klebsiella pneumoniae; multidrug-resistant bacteria;
targeted drug combination; ultra-high-throughput screen
ID ACINETOBACTER-BAUMANNII; ANTIBIOTIC-RESISTANCE; CYSTIC-FIBROSIS;
CLINICAL-TRIAL; INFECTIONS; THERAPY; PNEUMONIAE; MECHANISMS; CHALLENGES;
DISCOVERY
AB Current antimicrobial susceptibility testing has limited screening capability for identifying empirical antibiotic combinations to treat severe bacterial infections with multidrug-resistant (MDR) organisms. We developed a new antimicrobial susceptibility assay using automated ultra-high-throughput screen technology in combination with a simple bacterial growth assay. A rapid screening of 5170 approved drugs and other compounds identified 25 compounds with activities against MDR Klebsiella pneumoniae. To further improve the efficacy and reduce the effective drug concentrations, we applied a targeted drug combination approach that integrates drugs' clinical antimicrobial susceptibility breakpoints, achievable plasma concentrations, clinical toxicities and mechanisms of action to identify optimal drug combinations. Three sets of three-drug combinations were identified with broad-spectrum activities against 10 MDR clinical isolates including K. pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Citrobacter freundii, Enterobacter cloacae and Escherichia coli. Colistin-auranofin-ceftazidime and colistin-auranofin- rifabutin suppressed > 80% growth of all 10 MDR strains; while rifabutin-colistin-imipenem inhibited > 75% of these strains except two Acinetobacter baumannii isolates. The results demonstrate this new assay has potential as a real-time method to identify new drugs and effective drug combinations to combat severe clinical infections with MDR organisms.
C1 [Sun, Wei; Xu, Miao; Southall, Noel; Dai, Sheng; Shinn, Paul; Sanderson, Philip E.; Zheng, Wei] Natl Ctr Adv Translat Sci, NIH, Bethesda, MD 20892 USA.
[Weingarten, Rebecca A.; Frank, Karen M.] NIH, Ctr Clin, Dept Lab Med, Bethesda, MD 20892 USA.
[Williamson, Peter R.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
RP Zheng, W (reprint author), Natl Ctr Adv Translat Sci, NIH, Bethesda, MD 20892 USA.; Frank, KM (reprint author), NIH, Ctr Clin, Dept Lab Med, Bethesda, MD 20892 USA.; Williamson, PR (reprint author), NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
EM williamsonpr@mail.nih.gov; karen.frank@nih.gov; wzheng@mail.nih.gov
RI Zheng, Wei/J-8889-2014
OI Zheng, Wei/0000-0003-1034-0757
FU Intramural Research Program of National Center for Advancing
Translational Sciences, National Institutes of Health Clinical Center;
National Institute of Allergy and Infectious Diseases, National
Institutes of Health, Bethesda, MD, USA
FX We thank the compound management group at National Center for Advancing
Translational Sciences, National Institutes of Health (NM), for their
professional support. We also thank the clinical microbiology laboratory
technologists at the National Institutes of Health Clinical Center for
preparing and testing patient isolates. This work was supported by the
Intramural Research Program of National Center for Advancing
Translational Sciences, National Institutes of Health Clinical Center,
and National Institute of Allergy and Infectious Diseases, National
Institutes of Health, Bethesda, MD, USA.
NR 50
TC 0
Z9 0
U1 14
U2 14
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2222-1751
J9 EMERG MICROBES INFEC
JI Emerg. Microbes Infect.
PD NOV 9
PY 2016
VL 5
AR e116
DI 10.1038/emi.2016.123
PG 11
WC Immunology; Microbiology
SC Immunology; Microbiology
GA EC8XP
UT WOS:000388426700004
PM 27826141
ER
PT J
AU Hensch, NR
Karim, ZA
Druey, KM
Tansey, MG
Khasawneh, FT
AF Hensch, Nicole R.
Karim, Zubair A.
Druey, Kirk M.
Tansey, Malu G.
Khasawneh, Fadi T.
TI RGS10 Negatively Regulates Platelet Activation and Thrombogenesis
SO PLOS ONE
LA English
DT Article
ID PROTEIN-COUPLED RECEPTORS; OUTSIDE-IN; THROMBUS FORMATION; VASCULAR
INJURY; KAPPA-B; AGONISTS; PHOSPHORYLATION; SECRETION; NEURONS; COMPLEX
AB Regulators of G protein signaling (RGS) proteins act as GTPase activating proteins to negatively regulate G protein-coupled receptor (GPCR) signaling. Although several RGS proteins including RGS2, RGS16, RGS10, and RGS18 are expressed in human and mouse platelets, the respective unique function(s) of each have not been fully delineated. RGS10 is a member of the D/R12 subfamily of RGS proteins and is expressed in microglia, macrophages, megakaryocytes, and platelets. We used a genetic approach to examine the role (s) of RGS10 in platelet activation in vitro and hemostasis and thrombosis in vivo. GPCRinduced aggregation, secretion, and integrin activation was much more pronounced in platelets from Rgs10(-/-) mice relative to wild type (WT). Accordingly, these mice had markedly reduced bleeding times and were more susceptible to vascular injury-associated thrombus formation than control mice. These findings suggest a unique, non-redundant role of RGS10 in modulating the hemostatic and thrombotic functions of platelets in mice. RGS10 thus represents a potential therapeutic target to control platelet activity and/or hypercoagulable states.
C1 [Hensch, Nicole R.; Karim, Zubair A.; Khasawneh, Fadi T.] Western Univ Hlth Sci, Coll Pharm, Dept Pharmaceut Sci, Pomona, CA 91766 USA.
[Druey, Kirk M.] NIAID, Mol Signal Transduct Sect, Lab Allerg Dis, NIH, 10 Ctr Dr,Room 11S244B, Bethesda, MD 20892 USA.
[Tansey, Malu G.] Emory Univ, Sch Med, Dept Physiol, Atlanta, GA 30322 USA.
[Karim, Zubair A.; Khasawneh, Fadi T.] Univ Texas El Paso, Sch Pharm, Dept Pharmaceut Sci, 1101 N Campbell St, El Paso, TX 79902 USA.
RP Khasawneh, FT (reprint author), Western Univ Hlth Sci, Coll Pharm, Dept Pharmaceut Sci, Pomona, CA 91766 USA.; Khasawneh, FT (reprint author), Univ Texas El Paso, Sch Pharm, Dept Pharmaceut Sci, 1101 N Campbell St, El Paso, TX 79902 USA.
EM khasawneh@westemu.edu
FU College of Pharmacy, Western University of Health Sciences, Pomona, CA
FX This work was supported by funds from the College of Pharmacy, Western
University of Health Sciences, Pomona, CA (to F.T.K.).
NR 34
TC 0
Z9 0
U1 0
U2 0
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD NOV 9
PY 2016
VL 11
IS 11
AR e0165984
DI 10.1371/journal.pone.0165984
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EB9OG
UT WOS:000387724300071
PM 27829061
ER
PT J
AU Walther, S
Tietze, M
Czerny, CP
Konig, S
Diesterbeck, US
AF Walther, Stefanie
Tietze, Manfred
Czerny, Claus-Peter
Koenig, Sven
Diesterbeck, Ulrike S.
TI Development of a Bioinformatics Framework for the Detection of Gene
Conversion and the Analysis of Combinatorial Diversity in Immunoglobulin
Heavy Chains in Four Cattle Breeds
SO PLOS ONE
LA English
DT Article
ID MULTIPLE SEQUENCE ALIGNMENT; COMPLEMENTARITY-DETERMINING REGION-3;
BOVINE IGG REPERTOIRE; V-H FAMILY; VARIABLE REGION; SOMATIC
DIVERSIFICATION; ANTIBODY DIVERSITY; CHICKEN; GERMLINE; LOCUS
AB We have developed a new bioinformatics framework for the analysis of rearranged bovine heavy chain immunoglobulin (Ig) variable regions by combining and refining widely used alignment algorithms. This bioinformatics framework allowed us to investigate alignments of heavy chain framework regions (FRHs) and the separate alignments of FRHs and heavy chain complementarity determining regions (CDRHs) to determine their germline origin in the four cattle breeds Aubrac, German Black Pied, German Simmental, and Holstein Friesian. Now it is also possible to specifically analyze Ig heavy chains possessing exceptionally long CDR3Hs. In order to gain more insight into breed specific differences in Ig combinatorial diversity, somatic hypermutations and putative gene conversions of IgG, we compared the dominantly transcribed variable (IGHV), diversity (IGHD), and joining (IGHJ) segments and their recombination in the four cattle breeds. The analysis revealed the use of 15 different IGHV segments, 21 IGHD segments, and two IGHJ segments with significant different transcription levels within the breeds. Furthermore, there are preferred rearrangements within the three groups of CDR3H lengths. In the sequences of group 2 (CDR3H lengths (L) of 11-47 amino acid residues (aa)) a higher number of recombination was observed than in sequences of group 1 (L <= 10 aa) and 3 (L >= 48 aa). The combinatorial diversity of germline IGHV, IGHD, and IGHJ-segments revealed 162 rearrangements that were significantly different. The few preferably rearranged gene segments within group 3 CDR3H regions may indicate specialized antibodies because this length is unique in cattle. The most important finding of this study, which was enabled by using the bioinformatics framework, is the discovery of strong evidence for gene conversion as a rare event using pseudogenes fulfilling all definitions for this particular diversification mechanism.
C1 [Walther, Stefanie; Czerny, Claus-Peter; Diesterbeck, Ulrike S.] Georg August Univ Goettingen, Inst Vet Med, Fac Agr Sci, Dept Anim Sci,Div Microbiol & Anim Hyg, Gottingen, Germany.
[Tietze, Manfred; Koenig, Sven] Univ Kassel, Dept Anim Breeding, Witzenhausen, Germany.
[Diesterbeck, Ulrike S.] NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Diesterbeck, US (reprint author), Georg August Univ Goettingen, Inst Vet Med, Fac Agr Sci, Dept Anim Sci,Div Microbiol & Anim Hyg, Gottingen, Germany.; Diesterbeck, US (reprint author), NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA.
EM ulrike.diesterbeck@nih.gov
FU Georg-August University Goettingen [GAUGIVM9100010893]; German Research
Foundation (DFG); Open Access Publication Funds of the Gottingen
University
FX Stefanie Walther was supported by a scholarship provided by the
Georg-August University Goettingen (GAUGIVM9100010893). We acknowledge
support by the German Research Foundation (DFG) and the Open Access
Publication Funds of the Gottingen University. The funders had no role
in study design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 51
TC 0
Z9 0
U1 9
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 NOV 9
PY 2016
VL 11
IS 11
AR e0164567
DI 10.1371/journal.pone.0164567
PG 31
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EB9OG
UT WOS:000387724300018
PM 27828971
ER
PT J
AU Dinh, L
Chowell, G
Mizumoto, K
Nishiura, H
AF Dinh, Linh
Chowell, Gerardo
Mizumoto, Kenji
Nishiura, Hiroshi
TI Estimating the subcritical transmissibility of the Zika outbreak in the
State of Florida, USA, 2016
SO THEORETICAL BIOLOGY AND MEDICAL MODELLING
LA English
DT Article
DE Prediction; Zika virus; Epidemic; Mathematical model; Basic reproduction
number
ID EPIDEMIC
AB Background: Florida State has reported autochthonous transmission of Zika virus since late July 2016. Here we assessed the transmissibility associated with the outbreak and generated a short-term forecast.
Methods: Time-dependent dynamics of imported cases reported in the state of Florida was approximated by a logistic growth equation. We estimated the reproduction number using the renewal equation in order to predict the incidence of local cases arising from both local and imported primary cases. Using a bootstrap method together with the logistic and renewal equations, a short-term forecast of local and imported cases was carried out.
Results: The reproduction number was estimated at 0.16 (95 % Confidence Interval: 0.13, 0.19). Employing the logistic equation to capture a drastic decline in the number of imported cases expected through the course of 2016, together with the low estimate of the local reproduction number in Florida, the expected number of local reported cases was demonstrated to show an evident declining trend for the remainder of 2016.
Conclusions: The risk of local transmission in the state of Florida is predicted to dramatically decline by the end of 2016.
C1 [Dinh, Linh; Chowell, Gerardo] Georgia State Univ, Sch Publ Hlth, 1 Pk Pl, Atlanta, GA 30303 USA.
[Chowell, Gerardo] NIH, Div Int Epidemiol & Populat Studies, Fogarty Int Ctr, Bldg 10, Bethesda, MD 20892 USA.
[Mizumoto, Kenji; Nishiura, Hiroshi] Hokkaido Univ, Grad Sch Med, Kita Ku, Kita 15 Jo Nishi 7 Chome, Sapporo, Hokkaido 0608638, Japan.
[Mizumoto, Kenji; Nishiura, Hiroshi] Japan Sci & Technol Agcy, CREST, 4-1-8,Honcho, Kawaguchi, Saitama 3320012, Japan.
RP Nishiura, H (reprint author), Hokkaido Univ, Grad Sch Med, Kita Ku, Kita 15 Jo Nishi 7 Chome, Sapporo, Hokkaido 0608638, Japan.; Nishiura, H (reprint author), Japan Sci & Technol Agcy, CREST, 4-1-8,Honcho, Kawaguchi, Saitama 3320012, Japan.
EM nishiurah@med.hokudai.ac.jp
FU Japan Agency for Medical Research and Development; Japan Society for the
Promotion of Science (JSPS) KAKENHI Grant [16KT0130, 16 K15356,
26700028]; Program for Advancing Strategic International Networks; Japan
Science and Technology Agency (JST) CREST program; RISTEX program for
Science of Science, Technology and Innovation Policy; NSF [1414374]; UK
Biotechnology and Biological Sciences Research Council [BB/M008894/1];
NSF-IIS RAPID [1518939]; NSF: Small: Data Management for Real-Time Data
Driven Epidemic simulation [1318788 III]; Division of International
Epidemiology and Population Studies, The Fogarty International Center,
US National Institutes of Health
FX HN received funding support from the Japan Agency for Medical Research
and Development, the Japan Society for the Promotion of Science (JSPS)
KAKENHI Grant Numbers 16KT0130, 16 K15356 and 26700028, Program for
Advancing Strategic International Networks to Accelerate the Circulation
of Talented Researchers, the Japan Science and Technology Agency (JST)
CREST program and RISTEX program for Science of Science, Technology and
Innovation Policy. GC acknowledges financial support from the NSF grant
1414374 as part of the joint NSF-NIH-USDA Ecology and Evolution of
Infectious Diseases program; UK Biotechnology and Biological Sciences
Research Council grant BB/M008894/1, NSF-IIS RAPID award # 1518939, and
NSF grant 1318788 III: Small: Data Management for Real-Time Data Driven
Epidemic simulation, and the Division of International Epidemiology and
Population Studies, The Fogarty International Center, US 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 12
TC 1
Z9 1
U1 7
U2 7
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1742-4682
J9 THEOR BIOL MED MODEL
JI Theor. Biol. Med. Model.
PD NOV 9
PY 2016
VL 13
AR 20
DI 10.1186/s12976-016-0046-1
PG 7
WC Mathematical & Computational Biology
SC Mathematical & Computational Biology
GA EC2EJ
UT WOS:000387922200001
PM 27829439
ER
PT J
AU Bielekova, B
Tintore, M
AF Bielekova, Bibiana
Tintore, Mar
TI Sustained reduction of MS disability New player in comparing
disease-modifying treatments
SO NEUROLOGY
LA English
DT Editorial Material
ID REMITTING MULTIPLE-SCLEROSIS; CONTROLLED PHASE-3 TRIAL; ALEMTUZUMAB;
INFLAMMATION
C1 [Bielekova, Bibiana] NINDS, Neuroimmunol Dis Unit, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
[Tintore, Mar] Univ Autonoma Barcelona, Hosp Univ Vall dHebron, Dept Neurol Neuroimmunol, Ctr Esclerosi Multiple Catalunya Cemcat, E-08193 Barcelona, Spain.
RP Bielekova, B (reprint author), NINDS, Neuroimmunol Dis Unit, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
EM Bibi.Bielekova@nih.gov
FU intramural research program of the National Institute of Neurologic
Disorders and Stroke
FX The work of Dr. Bielekova was supported by the intramural research
program of the National Institute of Neurologic Disorders and Stroke.
NR 11
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0028-3878
EI 1526-632X
J9 NEUROLOGY
JI Neurology
PD NOV 8
PY 2016
VL 87
IS 19
BP 1966
EP 1967
DI 10.1212/WNL.0000000000003314
PG 2
WC Clinical Neurology
SC Neurosciences & Neurology
GA EI1JP
UT WOS:000392233600006
PM 27733564
ER
PT J
AU Nadkarni, NK
Boudreau, RM
Studenski, SA
Lopez, OL
Liu, G
Kritchevsky, S
Yaffe, K
Newman, AB
Rosano, C
AF Nadkarni, Neelesh K.
Boudreau, Robert M.
Studenski, Stephanie A.
Lopez, Oscar L.
Liu, Ge
Kritchevsky, Stephen
Yaffe, Kristine
Newman, Anne B.
Rosano, Caterina
TI Slow gait, white matter characteristics, and prior 10-year interleukin-6
levels in older adults
SO NEUROLOGY
LA English
DT Article
ID C-REACTIVE PROTEIN; INFLAMMATORY MARKERS; CARDIOVASCULAR HEALTH;
PHYSICAL PERFORMANCE; MR-IMAGES; DECLINE; BRAIN; HYPERINTENSITIES;
DIFFUSION; MOBILITY
AB Objective: To examine the relationship between gait speed and prior 10 years interleukin-6 (IL-6) burden in older adults. We then assessed whether white matter characteristics influence this relationship.
Methods: In 179 community-dwelling older adults, gait speed was assessed on an automated walkway and serum IL-6 was assayed on ELISA. Concurrently, white matter characteristics were assessed on MRI by quantifying volume of white matter hyperintensities (WMH), a marker of small vessel disease, and normal-appearing white matter on fractional anisotropy (NAWM-FA), a marker of axonal integrity. IL-6 was assayed at regular intervals at gait assessment and over the prior 10 years and estimates of sustained 10-year IL-6 exposure and the rate of change in IL-6 over 10 years were obtained. Multivariate linear regressions were used to examine the relationships among sustained IL-6 exposure, rate of change in IL-6, gait speed, and white matter characteristics.
Results: In this sample (age 83 years, 58% female, 41% black, gait speed 0.9 m/s), higher sustained IL-6 levels, but not the rate of change in IL-6 or IL-6 at gait assessment, was significantly related to slower gait (beta = -20.27, p < 0.001) and to higher WMH (beta = 0.23, p = 0.002), but not NAWM-FA, withstanding covariate adjustments. WMH accounted for 30% attenuation in the relationship between higher sustained IL-6 levels and slower gait speed (p = 0.043) in the mediation analyses.
Conclusions: Sustained exposure to high IL-6 over 10 years rather than the rate of change in IL-6 or an isolated high IL-6 level may adversely affect gait speed by influencing cerebral WMH.
C1 [Nadkarni, Neelesh K.] Univ Pittsburgh, Div Geriatr Med & Gerontol, Dept Med, Sch Med, Pittsburgh, PA 15260 USA.
[Lopez, Oscar L.] Univ Pittsburgh, Dept Neurol, Sch Med, Pittsburgh, PA 15260 USA.
[Nadkarni, Neelesh K.; Lopez, Oscar L.] Univ Pittsburgh, Pittsburgh Alzheimers Dis Res Ctr, Sch Med, Pittsburgh, PA 15260 USA.
[Boudreau, Robert M.; Liu, Ge; Newman, Anne B.; Rosano, Caterina] Univ Pittsburgh, Dept Epidemiol, Grad Sch Publ Hlth, Pittsburgh, PA 15260 USA.
[Kritchevsky, Stephen] Wake Forest Sch Med, Sticht Ctr Aging, Winston Salem, NC USA.
[Yaffe, Kristine] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA.
[Studenski, Stephanie A.] NIA, Longitudinal Studies Sect, Translat Gerontol Branch, Baltimore, MD 21224 USA.
RP Nadkarni, NK (reprint author), Univ Pittsburgh, Div Geriatr Med & Gerontol, Dept Med, Sch Med, Pittsburgh, PA 15260 USA.; Nadkarni, NK (reprint author), Univ Pittsburgh, Pittsburgh Alzheimers Dis Res Ctr, Sch Med, Pittsburgh, PA 15260 USA.
EM nkn3@pitt.edu
FU National Institute on Aging [K23AG049945, R01AG029232, N01AG62101,
N01AG62103, N01AG 62106]; Intramural Research Program of the NIH;
Pittsburgh Pepper Center [P30 AG024827]; Pittsburgh Alzheimer's Disease
Research Center [P50 AG005133]
FX This research was supported by National Institute on Aging awards
K23AG049945, R01AG029232, N01AG62101, N01AG62103, and N01AG 62106; the
Intramural Research Program of the NIH; the Pittsburgh Pepper Center
(P30 AG024827); and the Pittsburgh Alzheimer's Disease Research Center
(P50 AG005133).
NR 40
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0028-3878
EI 1526-632X
J9 NEUROLOGY
JI Neurology
PD NOV 8
PY 2016
VL 87
IS 19
BP 1993
EP 1999
DI 10.1212/WNL.0000000000003304
PG 7
WC Clinical Neurology
SC Neurosciences & Neurology
GA EI1JP
UT WOS:000392233600010
PM 27733566
ER
PT J
AU Luoni, A
Massart, R
Nieratschker, V
Nemoda, Z
Blasi, G
Gilles, M
Witt, SH
Suderman, MJ
Suomi, SJ
Porcelli, A
Rizzo, G
Fazio, L
Torretta, S
Rampino, A
Berry, A
Gass, P
Cirulli, F
Rietschel, M
Bertolino, A
Deuschle, M
Szyf, M
Riva, MA
AF Luoni, A.
Massart, R.
Nieratschker, V.
Nemoda, Z.
Blasi, G.
Gilles, M.
Witt, S. H.
Suderman, M. J.
Suomi, S. J.
Porcelli, A.
Rizzo, G.
Fazio, L.
Torretta, S.
Rampino, A.
Berry, A.
Gass, P.
Cirulli, F.
Rietschel, M.
Bertolino, A.
Deuschle, M.
Szyf, M.
Riva, M. A.
TI Ankyrin-3 as a molecular marker of early-life stress and vulnerability
to psychiatric disorders
SO TRANSLATIONAL PSYCHIATRY
LA English
DT Article
ID CONVERGENT FUNCTIONAL GENOMICS; DNA METHYLATION; BIPOLAR DISORDER;
PREFRONTAL CORTEX; WORKING-MEMORY; POSTSYNAPTIC DENSITY; PRENATAL
STRESS; NEUROPSYCHIATRIC DISORDERS; ASSOCIATION ANALYSIS;
BRAIN-DEVELOPMENT
AB Exposure to early-life stress (ELS) may heighten the risk for psychopathology at adulthood. Here, in order to identify common genes that may keep the memory of ELS through changes in their methylation status, we intersected methylome analyses performed in different tissues and time points in rats, non-human primates and humans, all characterized by ELS. We identified Ankyrin-3 (Ank3), a scaffolding protein with a strong genetic association for psychiatric disorders, as a gene persistently affected by stress exposure. In rats, Ank3 methylation and mRNA changes displayed a specific temporal profile during the postnatal development. Moreover, exposure to prenatal stress altered the interaction of ankyrin-G, the protein encoded by Ank3 enriched in the post-synaptic compartment, with PSD95. Notably, to model in humans a gene by early stress interplay on brain phenotypes during cognitive performance, we demonstrated an interaction between functional variation in Ank3 gene and obstetric complications on working memory in healthy adult subjects. Our data suggest that alterations of Ank3 expression and function may contribute to the effects of ELS on the development of psychiatric disorders.
C1 [Luoni, A.; Riva, M. A.] Univ Milan, Dept Pharmacol & Biomol Sci, Via Balzaretti 9, I-20133 Milan, Italy.
[Massart, R.; Nemoda, Z.; Suderman, M. J.; Szyf, M.] McGill Univ, Dept Pharmacol & Therapeut, Montreal, PQ, Canada.
[Nieratschker, V.; Witt, S. H.; Rietschel, M.] Heidelberg Univ, Med Fac Mannheim, Cent Inst Mental Hlth, Dept Genet Epidemiol Psychiat, Mannheim, Germany.
[Nieratschker, V.] Univ Tubingen, Dept Psychiat & Psychotherapy, Tubingen, Germany.
[Nemoda, Z.; Suderman, M. J.; Szyf, M.] McGill Univ, Sackler Inst Epigenet & Psychobiol, Montreal, PQ, Canada.
[Blasi, G.; Porcelli, A.; Rizzo, G.; Fazio, L.; Torretta, S.; Rampino, A.; Bertolino, A.] Univ Bari Aldo Moro, Dept Basic Med Sci Neurosci & Sense Organs, Bari, Italy.
[Gilles, M.; Gass, P.; Deuschle, M.] Heidelberg Univ, Med Fac Mannheim, Cent Inst Mental Hlth, Dept Psychiat & Psychotherapy, Mannheim, Germany.
[Suderman, M. J.] McGill Univ, McGill Ctr Bioinformat, Montreal, PQ, Canada.
[Suomi, S. J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Comparat Ethol Lab, NIH, Bethesda, MD USA.
[Berry, A.; Cirulli, F.] Ist Super Sanita, Dept Cell Biol & Neurosci, Rome, Italy.
RP Riva, MA (reprint author), Univ Milan, Dept Pharmacol & Biomol Sci, Via Balzaretti 9, I-20133 Milan, Italy.
EM M.Riva@unimi.it
OI Blasi, Giuseppe/0000-0003-0878-1131
FU ERANET Neuron grant; Italian Ministry of University and Research (PRIN)
[20107MSMA4_002]; Fondazione CARIPLO [2012-0503]; Dietmar Hopp
Foundation; Olympia-Morata-Programme of the University of Heidelberg;
Boehringer-Ingelheim Fonds; Fondazione Umberto Veronesi Fellowship;
Marie Curie International Outgoing Fellowship within the 7th European
Community Framework Programme; Canadian Institute of Health Research
[MOP-42411]
FX This work was supported by an ERANET Neuron grant to MD, MS, MAR and PG,
as well as by grants from the Italian Ministry of University and
Research to MAR (PRIN - grant number 20107MSMA4_002) and from Fondazione
CARIPLO (grant number 2012-0503) to MAR, FC and A Bertolino. In
addition, characterization of the human cohort was supported by a grant
of the Dietmar Hopp Foundation. VN received support from the
Olympia-Morata-Programme of the University of Heidelberg and the
Boehringer-Ingelheim Fonds. AL was supported by a Fondazione Umberto
Veronesi Fellowship. ZN was supported by Marie Curie International
Outgoing Fellowship within the 7th European Community Framework
Programme. Work in MS's laboratory was supported by Canadian Institute
of Health Research Grant MOP-42411. We are grateful to Elisa Zianni and
Dr Jennifer Stanic for the help with co-immunoprecipitation.
NR 83
TC 0
Z9 0
U1 2
U2 2
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 2158-3188
J9 TRANSL PSYCHIAT
JI Transl. Psychiatr.
PD NOV 8
PY 2016
VL 6
AR e943
DI 10.1038/tp.2016.211
PG 9
WC Psychiatry
SC Psychiatry
GA EI0AD
UT WOS:000392132700004
PM 27824361
ER
PT J
AU Marusak, HA
Thomason, ME
Peters, C
Zundel, C
Elrahal, F
Rabinak, CA
AF Marusak, H. A.
Thomason, M. E.
Peters, C.
Zundel, C.
Elrahal, F.
Rabinak, C. A.
TI You say 'prefrontal cortex' and I say 'anterior cingulate':
meta-analysis of spatial overlap in amygdala-to-prefrontal connectivity
and internalizing symptomology
SO TRANSLATIONAL PSYCHIATRY
LA English
DT Article
ID MAJOR DEPRESSIVE DISORDER; GENERALIZED ANXIETY DISORDER; FUNCTIONAL
CONNECTIVITY; BIPOLAR DISORDER; NETWORK; ACTIVATION; MATTER; BRAIN;
SCALE; SPECIALIZATION
AB Connections between the amygdala and medial prefrontal cortex (mPFC) are considered critical for the expression and regulation of emotional behavior. Abnormalities in frontoamygdala circuitry are reported across several internalizing conditions and associated risk factors (for example, childhood trauma), which may underlie the strong phenotypic overlap and co-occurrence of internalizing conditions. However, it is unclear if these findings converge on the same localized areas of mPFC or adjacent anterior cingulate cortex (ACC). Examining 46 resting-state functional connectivity magnetic resonance imaging studies of internalizing conditions or risk factors (for example, early adversity and family history), we conducted an activation likelihood estimation meta-analysis of frontoamygdala circuitry. We included all reported amygdala to frontal coordinate locations that fell within a liberal anatomically defined frontal mask. Peak effects across studies were centered in two focal subareas of the ACC: pregenual (pgACC) and subgenual (sgACC). Using publicly available maps and databases of healthy individuals, we found that observed subareas have unique connectivity profiles, patterns of neural co-activation across a range of neuropsychological tasks, and distribution of tasks spanning various behavioral domains within peak regions, also known as 'functional fingerprints'. These results suggest disruptions in unique amygdala-ACC subcircuits across internalizing, genetic and environmental risk studies. Based on functional characterizations and the studies contributing to each peak, observed amygdala-ACC subcircuits may reflect separate transdiagnostic neural signatures. In particular, they may reflect common neurobiological substrates involved in developmental risk (sgACC), or the broad expression of emotional psychopathology (pgACC) across disease boundaries.
C1 [Marusak, H. A.; Peters, C.; Elrahal, F.; Rabinak, C. A.] Wayne State Univ, Dept Pharm Practice, 259 Mack Ave,Suite 2190, Detroit, MI 48202 USA.
[Thomason, M. E.] Wayne State Univ, Merrill Palmer Skillman Inst Child & Family Dev, Detroit, MI USA.
[Thomason, M. E.] Wayne State Univ, Sch Med, Dept Pediat, Detroit, MI 48201 USA.
[Thomason, M. E.] NICHD, Unit Perinatal Neural Connect, Perinatol Res Branch, NIH,DHHS, Bethesda, MD USA.
[Zundel, C.] Boston Univ, Behav Neurosci, Boston, MA 02215 USA.
RP Marusak, HA (reprint author), Wayne State Univ, Dept Pharm Practice, 259 Mack Ave,Suite 2190, Detroit, MI 48202 USA.
EM hmarusak@med.wayne.edu
FU American Cancer Society award [129368-PF-16-057-01-PCSM]; National
Institutes of Health (NIH) National Institute of Mental Health [K01
MH101123]; NIH National Institute of Environmental Health Sciences [P30
ES020957, R21 ES026022]; NIH National Institute of Mental Health [R01
MH110793]
FX Dr Marusak is supported by American Cancer Society award
129368-PF-16-057-01-PCSM. Dr Rabinak is supported by National Institutes
of Health (NIH) National Institute of Mental Health award K01 MH101123.
Dr Thomason is supported by NIH National Institute of Environmental
Health Sciences awards P30 ES020957 and R21 ES026022, and NIH National
Institute of Mental Health award R01 MH110793. The funders had no role
in the design and conduct of the study; collection, management,
analysis, and interpretation of the data; preparation, review, or
approval of the manuscript; and design to submit the manuscript for
publication. The content is solely the responsibility of the authors and
does not necessarily represent the official views of the funding
agencies.
NR 54
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PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 2158-3188
J9 TRANSL PSYCHIAT
JI Transl. Psychiatr.
PD NOV 8
PY 2016
VL 6
AR e944
DI 10.1038/tp.2016.218
PG 10
WC Psychiatry
SC Psychiatry
GA EI0AD
UT WOS:000392132700005
PM 27824358
ER
PT J
AU Carlson, VR
Sheehan, FT
Boden, BP
AF Carlson, Victor R.
Sheehan, Frances T.
Boden, Barry P.
TI VIDEO ANALYSIS OF ANTERIOR CRUCIATE LIGAMENT (ACL) INJURIES A Systematic
Review
SO JBJS REVIEWS
LA English
DT Article
ID FEMALE TEAM HANDBALL; TIBIAL PLATEAU; BONE CONTUSION; SAGITTAL PLANE;
PROFESSIONAL FOOTBALL; VALGUS COLLAPSE; KNEE KINEMATICS; RISK-FACTORS;
MECHANISMS; PREVENTION
AB Background: As the most viable method for investigating in vivo anterior cruciate ligament (ACL) rupture, video analysis is critical for understanding ACL injury mechanisms and advancing preventative training programs. Despite the limited number of published studies involving video analysis, much has been gained through evaluating actual injury scenarios.
Methods: Studies meeting criteria for this systematic review were collected by performing a broad search of the ACL literature with use of variations and combinations of video recordings and ACL injuries. Both descriptive and analytical studies were included.
Results: Descriptive studies have identified specific conditions that increase the likelihood of an ACL injury. These conditions include close proximity to opposing players or other perturbations, high shoe-surface friction, and landing on the heel or the flat portion of the foot. Analytical studies have identified high-risk joint angles on landing, such as a combination of decreased ankle plantar flexion, decreased knee flexion, and increased hip flexion.
Conclusions: The high-risk landing position appears to influence the likelihood of ACL injury to a much greater extent than inherent risk factors. As such, on the basis of the results of video analysis, preventative training should be applied broadly. Kinematic data from video analysis have provided insights into the dominant forces that are responsible for the injury (i.e., axial compression with potential contributions from quadriceps contraction and valgus loading). With the advances in video technology currently underway, video analysis will likely lead to enhanced understanding of non-contact ACL injury.
C1 [Carlson, Victor R.; Sheehan, Frances T.; Boden, Barry P.] NIH, Ctr Clin, Bethesda, MD 20892 USA.
[Carlson, Victor R.; Sheehan, Frances T.] NIH, Funct & Appl Biomech, Bldg 10, Bethesda, MD 20892 USA.
[Boden, Barry P.] Orthopaed Ctr, Rockville, MD USA.
RP Sheehan, FT (reprint author), NIH, Funct & Appl Biomech, Bldg 10, Bethesda, MD 20892 USA.
EM gavellif@cc.nih.gov
FU National Institutes of Health (NIH), Clinical Center, Functional and
Applied Biomechanics Section; NIH
FX This research was supported by the Intramural Research Program of the
National Institutes of Health (NIH), Clinical Center, Functional and
Applied Biomechanics Section. This research was also made possible
through the NIH Medical Research Scholars Program, a public-private
partnership supported jointly by the NIH and generous contributions to
the Foundation for the NIH from Pfizer, the Leona M. and Harry B.
Helmsley Charitable Trust, and the Howard Hughes Medical Institute, as
well as other private donors. For a complete list, visit the website at
http://fnih.org. The authors also thank informationist Judith Welsh, NIH
Library, for editing this manuscript.
NR 66
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U1 3
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 2329-9185
J9 JBJS REV
JI JBJS Rev.
PD NOV 8
PY 2016
VL 4
IS 11
AR e5
DI 10.2106/JBJS.RVW.15.00116
PG 12
WC Surgery
SC Surgery
GA EG4SN
UT WOS:000391034100005
ER
PT J
AU Lin, WHW
Nish, SA
Yen, B
Chen, YH
Adams, WC
Kratchmarov, R
Rothman, NJ
Bhandoola, A
Xue, HH
Reiner, SL
AF Lin, Wen-Hsuan W.
Nish, Simone A.
Yen, Bonnie
Chen, Yen-Hua
Adams, William C.
Kratchmarov, Radomir
Rothman, Nyanza J.
Bhandoola, Avinash
Xue, Hai-Hui
Reiner, Steven L.
TI CD8(+) T Lymphocyte Self-Renewal during Effector Cell Determination
SO CELL REPORTS
LA English
DT Article
ID DNA METHYLATION; VIRAL-INFECTION; MEMORY; DIFFERENTIATION; DIVISION;
SPECIFICATION; TCF-1; FATES; ACTIVATION; EXPRESSION
AB Selected CD8(+) T cells must divide, produce differentiated effector cells, and self-renew, often repeatedly. We now show that silencing expression of the transcription factor TCF1 marks loss of self-renewal by determined effector cells and that this requires cell division. In acute infections, the first three CD8(+) T cell divisions produce daughter cells with unequal proliferative signaling but uniform maintenance of TCF1 expression. The more quiescent initial daughter cells resemble canonical central memory cells. The more proliferative, effector-prone cells from initial divisions can subsequently undergo division-dependent production of a TCF1-negative effector daughter cell along with a self-renewing TCF1-positive daughter cell, the latter also contributing to the memory cell pool upon resolution of infection. Self-renewal in the face of effector cell determination may promote clonal amplification and memory cell formation in acute infections, sustain effector regeneration during persistent subclinical infections, and be rate limiting, but remediable, in chronic active infections and cancer.
C1 [Lin, Wen-Hsuan W.; Nish, Simone A.; Yen, Bonnie; Chen, Yen-Hua; Adams, William C.; Kratchmarov, Radomir; Rothman, Nyanza J.; Reiner, Steven L.] Columbia Univ, Coll Phys & Surg, Dept Microbiol & Immunol, New York, NY 10032 USA.
[Lin, Wen-Hsuan W.; Nish, Simone A.; Yen, Bonnie; Chen, Yen-Hua; Adams, William C.; Kratchmarov, Radomir; Rothman, Nyanza J.; Reiner, Steven L.] Columbia Univ, Coll Phys & Surg, Dept Pediat, New York, NY 10032 USA.
[Bhandoola, Avinash] NCI, T Cell Biol & Dev Unit, Lab Genome Integr, Ctr Canc Res, Bethesda, MD 20892 USA.
[Xue, Hai-Hui] Univ Iowa, Dept Microbiol, Carver Coll Med, Iowa City, IA 52242 USA.
RP Reiner, SL (reprint author), Columbia Univ, Coll Phys & Surg, Dept Microbiol & Immunol, New York, NY 10032 USA.; Reiner, SL (reprint author), Columbia Univ, Coll Phys & Surg, Dept Pediat, New York, NY 10032 USA.
EM sr2978@cumc.columbia.edu
FU NIH [AI061699, AI113365, AI076458, AI112579, AI115149, AI119160,
AI121080]; U.S. Department of Veteran Affairs Merit Review Award [I01
BX002903]; Charles H. Revson Foundation
FX We are grateful to E.J. Wherry (University of Pennsylvania) for advice
and reagents. This study was supported by NIH grants AI061699, AI113365,
and AI076458 (to S.L.R.), AI112579, AI115149, AI119160, and AI121080 (to
H.-H.X.); the U.S. Department of Veteran Affairs Merit Review Award I01
BX002903 (to H.-H.X.); and the Charles H. Revson Foundation.
NR 34
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U1 2
U2 2
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 2211-1247
J9 CELL REP
JI Cell Reports
PD NOV 8
PY 2016
VL 17
IS 7
BP 1773
EP 1782
DI 10.1016/j.celrep.2016.10.032
PG 10
WC Cell Biology
SC Cell Biology
GA EF7YS
UT WOS:000390545900008
PM 27829149
ER
PT J
AU Zheng, XF
Yang, PY
Lackford, B
Bennett, BD
Wang, L
Li, H
Wang, Y
Miao, YL
Foley, JF
Fargo, DC
Jin, Y
Williams, CJ
Jothi, R
Hu, G
AF Zheng, Xiaofeng
Yang, Pengyi
Lackford, Brad
Bennett, Brian D.
Wang, Li
Li, Hui
Wang, Yu
Miao, Yiliang
Foley, Julie F.
Fargo, David C.
Jin, Ying
Williams, Carmen J.
Jothi, Raja
Hu, Guang
TI CNOT3-Dependent mRNA Deadenylation Safeguards the Pluripotent State
SO STEM CELL REPORTS
LA English
DT Article
ID EMBRYONIC STEM-CELLS; CCR4-NOT COMPLEX; SELF-RENEWAL; FACILITATES
PLURIPOTENCY; IN-VIVO; PROTEINS; GENOME; CNOT3; DIFFERENTIATION;
IDENTIFICATION
AB Poly(A) tail length and mRNA deadenylation play important roles in gene regulation. However, how they regulate embryonic development and pluripotent cell fate is not fully understood. Here we present evidence that CNOT3-dependent mRNA deadenylation governs the pluripotent state. We show that CNOT3, a component of the Ccr4-Not deadenylase complex, is required for mouse epiblast maintenance. It is highly expressed in blastocysts and its deletion leads to peri-implantation lethality. The epiblast cells in Cnot3 deletion embryos are quickly lost during diapause and fail to outgrow in culture. Mechanistically, CNOT3 C terminus is required for its interaction with the complex and its function in embryonic stem cells (ESCs). Furthermore, Cnot3 deletion results in increases in the poly(A) tail lengths, half-lives, and steady-state levels of differentiation gene mRNAs. The half-lives of CNOT3 target mRNAs are shorter in ESCs and become longer during normal differentiation. Together, we propose that CNOT3 maintains the pluripotent state by promoting differentiation gene mRNA deadenylation and degradation, and we identify poly(A) tail-length regulation as a post-transcriptional mechanism that controls pluripotency.
C1 [Zheng, Xiaofeng; Yang, Pengyi; Lackford, Brad; Wang, Li; Jothi, Raja; Hu, Guang] Natl Inst Environm Hlth Sci, Epigenet & Stem Cell Biol Lab, Res Triangle Pk, NC 27709 USA.
[Bennett, Brian D.; Fargo, David C.] Natl Inst Environm Hlth Sci, Integrat Bioinformat Support Grp, Res Triangle Pk, NC 27709 USA.
[Li, Hui; Jin, Ying] Shanghai Jiao Tong Univ, Lab Mol Dev Biol, Sch Med, Shanghai 200025, Peoples R China.
[Wang, Yu; Foley, Julie F.] Natl Inst Environm Hlth Sci, Cellular & Mol Pathol Branch, Res Triangle Pk, NC 27709 USA.
[Miao, Yiliang; Williams, Carmen J.] Natl Inst Environm Hlth Sci, Reprod & Dev Biol Lab, Res Triangle Pk, NC 27709 USA.
RP Hu, G (reprint author), Natl Inst Environm Hlth Sci, Epigenet & Stem Cell Biol Lab, Res Triangle Pk, NC 27709 USA.
EM hug4@niehs.nih.gov
OI Yang, Pengyi/0000-0003-1098-3138
FU Intramural Research Program of the NIH, National Institute of
Environmental Health Sciences [Z01ES102745, Z01ES102985, Z01ES102625]
FX We thank Dr. Anna-Katerina Hadjantonakis for helpful discussions. We
thank the NIEHS Animal, Epigenomics, Bioinformatics, Protein Expression,
Imaging, and Histology core facility for assistance with various
techniques and experiments. This study was supported in part by the
Intramural Research Program of the NIH, National Institute of
Environmental Health Sciences Z01ES102745 (to G.H.), Z01ES102985 (to
C.J.W.), and Z01ES102625 (to R.J.).
NR 56
TC 0
Z9 0
U1 0
U2 0
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 2213-6711
J9 STEM CELL REP
JI Stem Cell Rep.
PD NOV 8
PY 2016
VL 7
IS 5
BP 897
EP 910
DI 10.1016/j.stemcr.2016.09.007
PG 14
WC Cell & Tissue Engineering; Cell Biology
SC Cell Biology
GA EE3QH
UT WOS:000389509000007
PM 27746116
ER
PT J
AU Kishton, RJ
Sukumar, M
Restifo, NP
AF Kishton, Rigel J.
Sukumar, Madhusudhanan
Restifo, Nicholas P.
TI Arginine Arms T Cells to Thrive and Survive
SO Cell Metabolism
LA English
DT Editorial Material
ID METABOLISM; MEMORY; PATHWAYS
AB A clear role for cellular metabolism in regulating immune cell function has recently been established. In a recent issue of Cell, Geiger et al. (2016) demonstrate a role for intracellular arginine abundance in T cells for the promotion of oxidative metabolism, increased cell viability, persistence, and in vivo antitumor response.
C1 [Kishton, Rigel J.; Sukumar, Madhusudhanan; Restifo, Nicholas P.] NCI, Ctr Cell Based Therapy, NIH, Bethesda, MD 20892 USA.
[Kishton, Rigel J.; Sukumar, Madhusudhanan; Restifo, Nicholas P.] NCI, Surg Branch, NIH, Bldg 10, Bethesda, MD 20892 USA.
RP Restifo, NP (reprint author), NCI, Ctr Cell Based Therapy, NIH, Bethesda, MD 20892 USA.; Restifo, NP (reprint author), NCI, Surg Branch, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM restifo@nih.gov
NR 9
TC 0
Z9 0
U1 2
U2 2
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1550-4131
EI 1932-7420
J9 CELL METAB
JI Cell Metab.
PD NOV 8
PY 2016
VL 24
IS 5
BP 647
EP 648
DI 10.1016/j.cmet.2016.10.019
PG 2
WC Cell Biology; Endocrinology & Metabolism
SC Cell Biology; Endocrinology & Metabolism
GA EE3QC
UT WOS:000389508000003
PM 27829132
ER
PT J
AU Gui, DY
Sullivan, LB
Luengo, A
Hosios, AM
Bush, LN
Gitego, N
Davidson, SM
Freinkman, E
Thomas, CJ
Vander Heiden, MG
AF Gui, Dan Y.
Sullivan, Lucas B.
Luengo, Alba
Hosios, Aaron M.
Bush, Lauren N.
Gitego, Nadege
Davidson, Shawn M.
Freinkman, Elizaveta
Thomas, Craig J.
Vander Heiden, Matthew G.
TI Environment Dictates Dependence on Mitochondrial Complex I for NAD plus
and Aspartate Production and Determines Cancer Cell Sensitivity to
Metformin
SO Cell Metabolism
LA English
DT Article
ID RESPIRATORY-CHAIN; DIABETIC-PATIENTS; PROSTATE-CANCER; BREAST-CANCER;
LUNG-CANCER; METABOLISM; BIGUANIDES; INHIBITION; PHARMACOKINETICS;
TUMORIGENESIS
AB Metformin use is associated with reduced cancer mortality, but how metformin impacts cancer outcomes is controversial. Although metformin can act on cells autonomously to inhibit tumor growth, the doses of metformin that inhibit proliferation in tissue culture are much higher than what has been described in vivo. Here, we show that the environment drastically alters sensitivity to metformin and other complex I inhibitors. We find that complex I supports proliferation by regenerating nicotinamide adenine dinucleotide (NAD)+, and metformin's anti-proliferative effect is due to loss of NAD+/NADH homeostasis and inhibition of aspartate biosynthesis. However, complex I is only one of many inputs that determines the cellular NAD+/NADH ratio, and dependency on complex I is dictated by the activity of other pathways that affect NAD+ regeneration and aspartate levels. This suggests that cancer drug sensitivity and resistance are not intrinsic properties of cancer cells, and demonstrates that the environment can dictate sensitivity to therapies that impact cell metabolism.
C1 [Gui, Dan Y.; Sullivan, Lucas B.; Luengo, Alba; Hosios, Aaron M.; Bush, Lauren N.; Gitego, Nadege; Davidson, Shawn M.; Vander Heiden, Matthew G.] MIT, Koch Inst Integrat Canc Res, Cambridge, MA 02142 USA.
[Gui, Dan Y.; Sullivan, Lucas B.; Luengo, Alba; Hosios, Aaron M.; Bush, Lauren N.; Gitego, Nadege; Davidson, Shawn M.; Vander Heiden, Matthew G.] MIT, Dept Biol, 77 Massachusetts Ave, Cambridge, MA 02142 USA.
[Freinkman, Elizaveta] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA.
[Thomas, Craig J.] NIH, Chem Genom Ctr, Natl Ctr Adv Translat Sci, Bldg 10, Bethesda, MD 20892 USA.
[Vander Heiden, Matthew G.] Dana Farber Canc Inst, Boston, MA 02115 USA.
RP Vander Heiden, MG (reprint author), MIT, Koch Inst Integrat Canc Res, Cambridge, MA 02142 USA.; Vander Heiden, MG (reprint author), MIT, Dept Biol, 77 Massachusetts Ave, Cambridge, MA 02142 USA.; Vander Heiden, MG (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA.
EM mvh@mit.edu
FU Burroughs Wellcome Fund [SU2C]; Ludwig Center at the Massachusetts
Institute of Technology; NIH [P30CA1405141, GG006413, R01 CA168653, R01
CA201276, T32 GM007753]; American Cancer Society [PF-15-096-01-TBE];
National Science Foundation [GRFP DGE-1122374]
FX This work was supported by the Burroughs Wellcome Fund, SU2C, the Ludwig
Center at the Massachusetts Institute of Technology, and the NIH
(P30CA1405141, GG006413, R01 CA168653, and R01 CA201276) to M.G.V.H.,
NIH (T32 GM007753) to D.Y.G., a postdoctoral fellowship
(PF-15-096-01-TBE) from the American Cancer Society to L.B.S., and the
National Science Foundation (GRFP DGE-1122374) to A.L. and S.M.D. We
thank members of the M.G.V.H. laboratory for thoughtful discussion.
NR 54
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U1 5
U2 5
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1550-4131
EI 1932-7420
J9 CELL METAB
JI Cell Metab.
PD NOV 8
PY 2016
VL 24
IS 5
BP 716
EP 727
DI 10.1016/j.cmet.2016.09.006
PG 12
WC Cell Biology; Endocrinology & Metabolism
SC Cell Biology; Endocrinology & Metabolism
GA EE3QC
UT WOS:000389508000012
PM 27746050
ER
PT J
AU Leng, YK
Wu, WJ
Li, L
Lin, K
Sun, K
Chen, XY
Li, WW
AF Leng, Yuankui
Wu, Weijie
Li, Li
Lin, Kun
Sun, Kang
Chen, Xiaoyuan
Li, Wanwan
TI Magnetic/Fluorescent Barcodes Based on Cadmium-Free
Near-Infrared-Emitting Quantum Dots for Multiplexed Detection
SO ADVANCED FUNCTIONAL MATERIALS
LA English
DT Article
ID MAGNETIC SEPARATION; SUSPENSION ARRAY; FLOW-CYTOMETRY; BEADS;
NANOCRYSTALS; MICROSPHERES; ENRICHMENT; MICROBEADS; CELLS; NANOPARTICLES
AB Magnetic/fluorescent barcodes, which combine quantum dots (QDs) and superparamagnetic nanoparticles in micrometer-sized host microspheres, are promising for automatic high-throughput multiplexed biodetection applications and "point of care" biodetection. However, the fluorescence intensity of QDs sharply decreases after addition of magnetic nanoparticles (MNPs) due to absorption by MNPs, and thus, the encoding capacity of QDs becomes more limited. Furthermore, the intrinsic toxicity of cadmium-based QDs, the most commonly used QD in barcodes, has significant risks to human health and the environment. In this work, to alleviate fluorescence quenching and intrinsic toxicity, cadmium-free NIR-emitting CuInS2/ZnS QDs and Fe3O4 MNPs are successfully incorporated into poly(styrene-co-maleic anhydride) microspheres by using the Shirasu porous glass membrane emulsification technique. A "single-wavelength" encoding model is successfully constructed to guide the encoding of NIR QDs with wide emission spectra. Then, a "single-wavelength" encoding combined with size encoding is used to produce different optical codes by simply changing the wavelength and the intensity of the QDs as well as the size of the barcode microspheres. 48 barcodes are easily created due to the greatly reduced energy transfer between the NIR-emitting QDs and MNPs. The resulting bifunctional barcodes are also combined with a flow cytometer using one laser for multiplexed detection of five tumor markers in one test. Assays based on these barcodes are significantly more sensitive than non-magnetic and traditional ELISA assays. Moreover, validating experiments also show good performance of the bifunctional barcodes-based suspension array when dealing with patient serum samples. Thus, magnetic/fluorescent barcodes based on NIR-emitting CuInS2/ZnS QDs are promising for multiplexed bioassay applications.
C1 [Leng, Yuankui; Wu, Weijie; Sun, Kang; Li, Wanwan] Shanghai Jiao Tong Univ, Sch Mat Sci & Engn, State Key Lab Met Matrix Composites, 800 Dongchuan Rd, Shanghai 200240, Peoples R China.
[Li, Li; Lin, Kun] Shanghai Jiao Tong Univ, Sch Med, Peoples Hosp 1, Shanghai 200080, Peoples R China.
[Chen, Xiaoyuan] NIBIB, Lab Mol Imaging & Nanomed LOMIN, NIH, Bethesda, MD 20892 USA.
RP Li, WW (reprint author), Shanghai Jiao Tong Univ, Sch Mat Sci & Engn, State Key Lab Met Matrix Composites, 800 Dongchuan Rd, Shanghai 200240, Peoples R China.
EM wwli@sjtu.edu.cn
FU National Natural Science Foundation of China [81371645]; Science and
Technology Committee of Shanghai [15PJD020, 15441905800, 16JC1400604];
Medicine and Engineering Cross Research Foundation of Shanghai Jiao Tong
University [YG2012MS61, YG2014MS33]
FX This work was financially supported by National Natural Science
Foundation of China (Project No. 81371645), Science and Technology
Committee of Shanghai (Project Nos. 15PJD020, 15441905800, and
16JC1400604), and Medicine and Engineering Cross Research Foundation of
Shanghai Jiao Tong University (Project Nos. YG2012MS61 and YG2014MS33).
The authors thank Instrumental Analysis Center of SJTU for the
assistance with TEM, SEM, VSM, and XRD characterizations.
NR 44
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U1 35
U2 35
PU WILEY-V C H VERLAG GMBH
PI WEINHEIM
PA POSTFACH 101161, 69451 WEINHEIM, GERMANY
SN 1616-301X
EI 1616-3028
J9 ADV FUNCT MATER
JI Adv. Funct. Mater.
PD NOV 8
PY 2016
VL 26
IS 42
BP 7581
EP 7589
DI 10.1002/adfm.201602900
PG 9
WC Chemistry, Multidisciplinary; Chemistry, Physical; Nanoscience &
Nanotechnology; Materials Science, Multidisciplinary; Physics, Applied;
Physics, Condensed Matter
SC Chemistry; Science & Technology - Other Topics; Materials Science;
Physics
GA EC5IC
UT WOS:000388166700004
ER
PT J
AU Srimuang, K
Miotto, O
Lim, P
Fairhurst, RM
Kwiatkowski, DP
Woodrow, CJ
Imwong, M
AF Srimuang, Krongkan
Miotto, Olivo
Lim, Pharath
Fairhurst, Rick M.
Kwiatkowski, Dominic P.
Woodrow, Charles J.
Imwong, Mallika
CA Tracking Resistance Artemisinin
TI Analysis of anti-malarial resistance markers in pfmdr1 and pfcrt across
Southeast Asia in the Tracking Resistance to Artemisinin Collaboration
SO MALARIA JOURNAL
LA English
DT Article
DE Malaria; Plasmodium falciparum; Anti-malarial resistance; Chloroquine;
Amodiaquine; Mefloquine; Artemisinin; Combination therapy; pfcrt; pfmdr1
ID PLASMODIUM-FALCIPARUM MALARIA; THAI-MYANMAR BORDER; GENE COPY NUMBER;
CHLOROQUINE-RESISTANCE; DIHYDROARTEMISININ-PIPERAQUINE; IN-VITRO;
ARTESUNATE-AMODIAQUINE; COMBINATION THERAPY; ARTEMETHER-LUMEFANTRINE;
MEFLOQUINE RESISTANCE
AB Background: Declining anti-malarial efficacy of artemisinin-based combination therapy, and reduced Plasmodium falciparum susceptibility to individual anti-malarials are being documented across an expanding area of Southeast Asia (SEA). Genotypic markers complement phenotypic studies in assessing the efficacy of individual anti-malarials.
Methods: The markers pfmdr1 and pfcrt were genotyped in parasite samples obtained in 2011-2014 at 14 TRAC (Tracking Resistance to Artemisinin Collaboration) sites in mainland Southeast Asia using a combination of PCR and next-generation sequencing methods.
Results: Pfmdr1 amplification, a marker of mefloquine and lumefantrine resistance, was highly prevalent at Mae Sot on the Thailand-Myanmar border (59.8% of isolates) and common (more than 10%) at sites in central Myanmar, eastern Thailand and western Cambodia; however, its prevalence was lower than previously documented in Pailin, western Cambodia. The pfmdr1 Y184F mutation was common, particularly in and around Cambodia, and the F1226Y mutation was found in about half of samples in Mae Sot. The functional significance of these two mutations remains unclear. Other previously documented pfmdr1 mutations were absent or very rare in the region. The pfcrt mutation K76T associated with chloroquine resistance was found in 98.2% of isolates. The CVIET haplotype made up 95% or more of isolates in western SEA while the CVIDT haplotype was common (30-40% of isolates) in north and northeastern Cambodia, southern Laos, and southern Vietnam.
Conclusions: These findings generate cause for concern regarding the mid-term efficacy of artemether-lumefantrine in Myanmar, while the absence of resistance-conferring pfmdr1 mutations and SVMNT pfcrt haplotypes suggests that amodiaquine could be an efficacious component of anti-malarial regimens in SEA.
C1 [Srimuang, Krongkan; Imwong, Mallika] Mahidol Univ, Fac Trop Med, Dept Mol Trop Med & Genet, Bangkok, Thailand.
[Miotto, Olivo; Woodrow, Charles J.; Imwong, Mallika] Mahidol Oxford Trop Med Res Unit, Bangkok, Thailand.
[Miotto, Olivo; Kwiatkowski, Dominic P.] Wellcome Trust Sanger Inst, Hinxton, England.
[Miotto, Olivo; Kwiatkowski, Dominic P.] Univ Oxford, MRC, Ctr Genom & Global Hlth, Oxford, England.
[Lim, Pharath; Fairhurst, Rick M.] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA.
[Woodrow, Charles J.] Univ Oxford, Nuffield Dept Med, Ctr Trop Med & Global Hlth, Oxford, England.
RP Imwong, M (reprint author), Mahidol Univ, Fac Trop Med, Dept Mol Trop Med & Genet, Bangkok, Thailand.
EM noi@tropmedres.ac
FU Royal Golden Jubilee Ph.D. Programme; Thailand Research Fund; Mahidol
University; Wellcome Trust of Great Britain; Wellcome Trust through core
funding of the Wellcome Trust Sanger Institute [098051]; Wellcome Trust
Centre for Human Genetics [090532/Z/09/Z]; Resource Centre for Genomic
Epidemiology of Malaria [090770/Z/09/Z]; UK Medical Research Council
[G0600718, MR/M006212/1]; Bill and Melinda Gates Foundation
[OPP1040463]; UK Department for International Development; Worldwide
Anti-malarial Resistance Network (WWARN); Intramural Research Program of
the National Institute of Allergy and Infectious Diseases, US National
Institutes of Health
FX PCR work in Thailand was funded by the Royal Golden Jubilee Ph.D.
Programme, the Thailand Research Fund, and Mahidol University. The
Mahidol-Oxford Tropical Medicine Research Programme is funded by the
Wellcome Trust of Great Britain. Whole-genome sequencing for this study
was funded by the Wellcome Trust through core funding of the Wellcome
Trust Sanger Institute (098051). The Wellcome Trust also supports the
Wellcome Trust Centre for Human Genetics (090532/Z/09/Z) and the
Resource Centre for Genomic Epidemiology of Malaria (090770/Z/09/Z). The
Centre for Genomics and Global Health is supported by the UK Medical
Research Council (G0600718, MR/M006212/1). This work was funded in part
by the Bill and Melinda Gates Foundation (OPP1040463). The fieldwork to
obtain samples was supported by grants from the UK Department for
International Development, the Worldwide Anti-malarial Resistance
Network (WWARN), and the Intramural Research Program of the National
Institute of Allergy and Infectious Diseases, US National Institutes of
Health. The views expressed and information contained in this article
are not necessarily those of or endorsed by the UK Department for
International Development or by the other funders, which can accept no
responsibility for such views or for any reliance placed on them.
NR 62
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U1 1
U2 1
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 NOV 8
PY 2016
VL 15
AR 541
DI 10.1186/s12936-016-1598-6
PG 12
WC Infectious Diseases; Parasitology; Tropical Medicine
SC Infectious Diseases; Parasitology; Tropical Medicine
GA EC5AA
UT WOS:000388144300006
PM 27825353
ER
PT J
AU Kong, L
Lee, DE
Kadam, RU
Liu, T
Giang, E
Nieusma, T
Garces, F
Tzarum, N
Woods, VL
Ward, AB
Li, S
Wilson, IA
Law, M
AF Kong, Leopold
Lee, David E.
Kadam, Rameshwar U.
Liu, Tong
Giang, Erick
Nieusma, Travis
Garces, Fernando
Tzarum, Netanel
Woods, Virgil L., Jr.
Ward, Andrew B.
Li, Sheng
Wilson, Ian A.
Law, Mansun
TI Structural flexibility at a major conserved antibody target on hepatitis
C virus E2 antigen
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE hepatitis C virus; E2; CD81-binding site; conformational flexibility;
protein dynamics
ID BROADLY NEUTRALIZING ANTIBODIES; AMIDE HYDROGEN/DEUTERIUM EXCHANGE;
SUSTAINED VIROLOGICAL RESPONSE; ENVELOPE GLYCOPROTEIN COMPLEX;
MOLECULAR-DYNAMICS; HIV-1 GP120; MEDIATED NEUTRALIZATION;
MONOCLONAL-ANTIBODIES; ELECTRON-MICROSCOPY; MASS-SPECTROMETRY
AB Hepatitis C virus (HCV) is a major cause of liver disease, affecting over 2% of the world's population. The HCV envelope glycoproteins E1 and E2 mediate viral entry, with E2 being the main target of neutralizing antibody responses. Structural investigations of E2 have produced templates for vaccine design, including the conserved CD81 receptor-binding site (CD81bs) that is a key target of broadly neutralizing antibodies (bNAbs). Unfortunately, immunization with recombinant E2 and E1E2 rarely elicits sufficient levels of bNAbs for protection. To understand the challenges for eliciting bNAb responses against the CD81bs, we investigated the E2 CD81bs by electron microscopy (EM), hydrogen-deuterium exchange (HDX), molecular dynamics (MD), and calorimetry. By EM, we observed that HCV1, a bNAb recognizing the N-terminal region of the CD81bs, bound a soluble E2 core construct from multiple angles of approach, suggesting components of the CD81bs are flexible. HDX of multiple E2 constructs consistently indicated the entire CD81bs was flexible relative to the rest of the E2 protein, which was further confirmed by MD simulations. However, E2 has a high melting temperature of 84.8 degrees C, which is more akin to proteins from thermophilic organisms. Thus, recombinant E2 is a highly stable protein overall, but with an exceptionally flexible CD81bs. Such flexibility may promote induction of nonneutralizing antibodies over bNAbs to E2 CD81bs, underscoring the necessity of rigidifying this antigenic region as a target for rational vaccine design.
C1 [Kong, Leopold; Kadam, Rameshwar U.; Nieusma, Travis; Garces, Fernando; Tzarum, Netanel; Ward, Andrew B.; Wilson, Ian A.] Scripps Res Inst, Dept Integrat Struct & Computat Biol, La Jolla, CA 92037 USA.
[Lee, David E.; Liu, Tong; Woods, Virgil L., Jr.; Li, Sheng] Univ Calif San Diego, Dept Med, La Jolla, CA 92037 USA.
[Giang, Erick; Law, Mansun] Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA.
[Wilson, Ian A.] Scripps Res Inst, Skaggs Inst Chem Biol, La Jolla, CA 92037 USA.
[Kong, Leopold] NIDDK, Struct Cell Biol Sect, Lab Cell & Mol Biol, NIH, Bethesda, MD 20814 USA.
RP Wilson, IA (reprint author), Scripps Res Inst, Dept Integrat Struct & Computat Biol, La Jolla, CA 92037 USA.; Law, M (reprint author), Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA.; Wilson, IA (reprint author), Scripps Res Inst, Skaggs Inst Chem Biol, La Jolla, CA 92037 USA.
EM wilson@scripps.edu; mlaw@scripps.edu
FU Swiss National Science Foundation; NIH [AI079031, AI123861, AI106005,
AI123365, GM094586, AI117905, GM020501, AI101436]; Skaggs Institute
FX R.U.K. thanks the Swiss National Science Foundation for a postdoctoral
fellowship. This work is supported by NIH Grants AI079031 and AI123861
(to M.L.); NIH Grants AI106005 and AI123365 (to M.L. and I.A.W.); NIH
Grant GM094586 (to I.A.W.); and NIH Grants AI117905, GM020501, and
AI101436 (to S.L.), as well as the Skaggs Institute (I.A.W.). This
article is manuscript 29353 from The Scripps Research Institute.
NR 72
TC 1
Z9 1
U1 8
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 NOV 8
PY 2016
VL 113
IS 45
BP 12768
EP 12773
DI 10.1073/pnas.1609780113
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EC4CL
UT WOS:000388073300067
ER
PT J
AU Kerbl, A
Fofanova, EG
Mayorova, TD
Voronezhskaya, EE
Worsaae, K
AF Kerbl, Alexandra
Fofanova, Elizaveta G.
Mayorova, Tatiana D.
Voronezhskaya, Elena E.
Worsaae, Katrine
TI Comparison of neuromuscular development in two dinophilid species
(Annelida) suggests progenetic origin of Dinophilus gyrociliatus
SO FRONTIERS IN ZOOLOGY
LA English
DT Article
DE Meiofauna evolution; Paedomorphosis; Sexual dimorphism; Sister species;
Nervous system; Musculature; Ciliation; Interstitial
ID VENTRAL PHARYNGEAL ORGANS; POLYCHAETA ANNELIDA; NERVOUS-SYSTEM;
PHYLOGENETIC IMPORTANCE; SEX-RATIO; SP-NOV.; HETEROCHRONY; EVOLUTION;
ARCHIANNELIDA; ULTRASTRUCTURE
AB Background: Several independent meiofaunal lineages are suggested to have originated through progenesis, however, morphological support for this heterochronous process is still lacking. Progenesis is defined as an arrest of somatic development (synchronously in various organ systems) due to early maturation, resulting in adults resembling larvae or juveniles of the ancestors. Accordingly, we established a detailed neuromuscular developmental atlas of two closely related Dinophilidae using immunohistochemistry and CLSM. This allows us to test for progenesis, questioning whether i) the adult smaller, dimorphic Dinophilus gyrociliatus resembles a younger developmental stage of the larger, monomorphic D. taeniatus and whether ii) dwarf males of D. gyrociliatus resemble an early developmental stage of D. gyrociliatus females.
Results: Both species form longitudinal muscle bundles first, followed by circular muscles, creating a grid of body wall musculature, which is the densest in adult D. taeniatus, while the architecture in adult female D. gyrociliatus resembles that of prehatching D. taeniatus. Both species display a subepidermal ganglionated nervous system with an anterior dorsal brain and five longitudinal ventral nerve bundles with six sets of segmental commissures (associated with paired ganglia). Neural differentiation of D. taeniatus and female D. gyrociliatus commissures occurs before hatching: both species start out forming one transverse neurite bundle per segment, which are thereafter joined by additional thin bundles. Whereas D. gyrociliatus arrests its development at this stage, adult D. taeniatus condenses the thin commissures again into one thick commissural bundle per segment. Generally, D. taeniatus adults demonstrate a seemingly more organized (= segmental) pattern of serotonin-like and FMRFamide-like immunoreactive elements. The dwarf male of D. gyrociliatus displays a highly aberrant neuromuscular system, showing no close resemblance to any early developmental stage of female Dinophilus, although the onset of muscular development mirrors the early myogenesis in females.
Conclusion: The apparent synchronous arrest of nervous and muscular development in adult female D. gyrociliatus, resembling the prehatching stage of D. taeniatus, suggests that D. gyrociliatus have originated through progenesis. The synchrony in arrest of three organ systems, which show opposing reduction and addition of elements, presents one of the morphologically best-argued cases of progenesis within Spiralia.
C1 [Kerbl, Alexandra; Worsaae, Katrine] Univ Copenhagen, Dept Biol, Marine Biol Sect, Univ Parken 4, DK-2100 Copenhagen, Denmark.
[Fofanova, Elizaveta G.; Mayorova, Tatiana D.; Voronezhskaya, Elena E.] RAS, Koltzov Inst Dev Biol, Lab Dev Neurobiol, 26 Vavilova Str, Moscow, Russia.
[Mayorova, Tatiana D.] NINDS, Lab Neurobiol, NIH, 49 Convent Dr, Bethesda, MD 20824 USA.
RP Worsaae, K (reprint author), Univ Copenhagen, Dept Biol, Marine Biol Sect, Univ Parken 4, DK-2100 Copenhagen, Denmark.; Mayorova, TD (reprint author), RAS, Koltzov Inst Dev Biol, Lab Dev Neurobiol, 26 Vavilova Str, Moscow, Russia.; Mayorova, TD (reprint author), NINDS, Lab Neurobiol, NIH, 49 Convent Dr, Bethesda, MD 20824 USA.
EM mayorova@wsbs-msu.ru; kworsaae@bio.ku.dk
OI Kerbl, Alexandra/0000-0002-9454-6359
FU Russian Foundation for Basic Research [15-04-04298, 15-29-02650]; Villum
Foundation [1025442]
FX A. Martinez, M. DiDomenico, N. Bekkouche, B. Gonzalez and RM. Kristensen
are thanked for their help collecting specimens of D. taeniatus in Disko
Island, Greenland and in Lysekil, Sweden. Furthermore, K. Kvindebjerg is
thanked for her help with unravelling myogenesis in the dwarf male of D.
gyrociliatus. We are furthermore grateful to the staff of the Pertsov
White Sea Biological Station, Russia as well as the people of the Arctic
Station, Disko Island, West Greenland for their generous assistance. The
authors thank the Optical Research Group of IDB RAS for technical
assistance. We are very grateful for the detailed comments provided by
E. Seaver, G. Purschke and two anonymous reviewers, which significantly
improved the manuscript. This work was partially supported by the
Russian Foundation for Basic Research (grants. 15-04-04298 to TDM and No
15-29-02650 to EEV) and by the Villum Foundation (grant No 1025442 to K.
Worsaae).
NR 83
TC 0
Z9 0
U1 8
U2 8
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1742-9994
J9 FRONT ZOOL
JI Front. Zool.
PD NOV 8
PY 2016
VL 13
AR 49
DI 10.1186/s12983-016-0181-x
PG 39
WC Zoology
SC Zoology
GA EB9TN
UT WOS:000387740100001
PM 27833644
ER
PT J
AU Twitchell, EL
Tin, C
Wen, K
Zhang, HS
Becker-Dreps, S
Azcarate-Peril, MA
Vilchez, S
Li, GH
Ramesh, A
Weiss, M
Lei, SH
Bui, T
Yang, XD
Schultz-Cherry, S
Yuan, LJ
AF Twitchell, Erica L.
Tin, Christine
Wen, Ke
Zhang, Husen
Becker-Dreps, Sylvia
Azcarate-Peril, M. Andrea
Vilchez, Samuel
Li, Guohua
Ramesh, Ashwin
Weiss, Mariah
Lei, Shaohua
Bui, Tammy
Yang, Xingdong
Schultz-Cherry, Stacey
Yuan, Lijuan
TI Modeling human enteric dysbiosis and rotavirus immunity in gnotobiotic
pigs
SO GUT PATHOGENS
LA English
DT Article
DE Enteric dysbiosis; Gnotobiotic pig; Rotavirus; Vaccine; Enteric immunity
ID ISOTYPE ANTIBODY-RESPONSES; POLYMERASE-CHAIN-REACTION; ENVIRONMENTAL
ENTEROPATHY; GUT MICROBIOTA; KLEBSIELLA-PNEUMONIAE; MATERNAL ANTIBODIES;
CELL RESPONSES; PROTECTIVE IMMUNITY; PCR ASSAYS; INFECTION
AB Background: Rotavirus vaccines have poor efficacy in infants from low- and middle-income countries. Gut microbiota is thought to influence the immune response to oral vaccines. Thus, we developed a gnotobiotic (Gn) pig model of enteric dysbiosis to study the effects of human gut microbiota (HGM) on immune responses to rotavirus vaccination, and the effects of rotavirus challenge on the HGM by colonizing Gn pigs with healthy HGM (HHGM) or unhealthy HGM (UHGM). The UHGM was from a Nicaraguan infant with a high enteropathy score (ES) and no seroconversion following administration of oral rotavirus vaccine, while the converse was characteristic of the HHGM. Pigs were vaccinated, a subset was challenged, and immune responses and gut microbiota were evaluated.
Results: Significantly more rotavirus-specific IFN-gamma producing T cells were in the ileum, spleen, and blood of HHGM than those in UHGM pigs after three vaccine doses, suggesting HHGM induces stronger cell-mediated immunity than UHGM. There were significant correlations between multiple Operational Taxonomic Units (OTUs) and frequencies of IFN-gamma producing T cells at the time of challenge. There were significant positive correlations between Collinsella and CD8+ T cells in blood and ileum, as well as CD4+ T cells in blood, whereas significant negative correlations between Clostridium and Anaerococcus, and ileal CD8+ and CD4+ T cells. Differences in alpha diversity and relative abundances of OTUs were detected between the groups both before and after rotavirus challenge.
Conclusion: Alterations in microbiome diversity and composition along with correlations between certain microbial taxa and T cell responses warrant further investigation into the role of the gut microbiota and certain microbial species on enteric immunity. Our results support the use of HGM transplanted Gn pigs as a model of human dysbiosis during enteric infection, and oral vaccine responses.
C1 [Twitchell, Erica L.; Tin, Christine; Wen, Ke; Li, Guohua; Ramesh, Ashwin; Weiss, Mariah; Lei, Shaohua; Bui, Tammy; Yang, Xingdong; Yuan, Lijuan] Virginia Polytech Inst & State Univ, Virginia Maryland Coll Vet Med, Dept Biomed Sci & Pathobiol, Blacksburg, VA 24061 USA.
[Zhang, Husen] NCI, Microbiome Core, Canc Inflammat Program, Bethesda, MD 20892 USA.
[Becker-Dreps, Sylvia] Univ N Carolina, Sch Med, Dept Family Med, Chapel Hill, NC USA.
[Azcarate-Peril, M. Andrea] Univ N Carolina, Dept Cell Biol & Physiol, Sch Med, Chapel Hill, NC USA.
[Azcarate-Peril, M. Andrea] Univ N Carolina, Microbiome Core Facil, Ctr Gastrointestinal Biol & Dis, Chapel Hill, NC USA.
[Vilchez, Samuel] Natl Autonomous Univ Nicaragua, Dept Microbiol & Parasitol, Fac Med Sci, Leon, Nicaragua.
[Schultz-Cherry, Stacey] St Jude Childrens Res Hosp, Dept Infect Dis, 332 N Lauderdale St, Memphis, TN 38105 USA.
RP Yuan, LJ (reprint author), Virginia Polytech Inst & State Univ, Virginia Maryland Coll Vet Med, Dept Biomed Sci & Pathobiol, Blacksburg, VA 24061 USA.
EM lyuan@vt.edu
FU Bill and Melinda Gates Foundation [OPP1108188]; Virginia Tech Graduate
Student Assembly Graduate Research and Development Fund; Ruth L.
Kirschstein Institutional National Research Service Award from the
National Institutes of Health
FX This work was supported by the Bill and Melinda Gates Foundation
(http://www.gatesfoundation.org) Grant # OPP1108188 to LY. A Virginia
Tech Graduate Student Assembly Graduate Research and Development Fund
Award (Spring 2015) provided financial support for the porcine
enteropathy ELISA kits. Erica Twitchell is supported by a Ruth L.
Kirschstein Institutional National Research Service Award from the
National Institutes of Health. The funding body had no role in the
design of the study, or collection, analysis, or interpretation of data,
or writing the manuscript.
NR 60
TC 0
Z9 0
U1 8
U2 8
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1757-4749
J9 GUT PATHOG
JI Gut Pathogens
PD NOV 8
PY 2016
VL 8
AR 51
DI 10.1186/s13099-016-0136-y
PG 18
WC Gastroenterology & Hepatology; Microbiology
SC Gastroenterology & Hepatology; Microbiology
GA EB3ON
UT WOS:000387275000001
PM 27826359
ER
PT J
AU Clayton, JA
Tannenbaum, C
AF Clayton, Janine Austin
Tannenbaum, Cara
TI Reporting Sex, Gender, or Both in Clinical Research?
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Editorial Material
C1 [Clayton, Janine Austin] NIH, Off Res Womens Hlth, 6707 Democracy Blvd, Bethesda, MD 20817 USA.
[Tannenbaum, Cara] Canadian Inst Hlth Res, Inst Gender & Hlth, Montreal, PQ, Canada.
RP Clayton, JA (reprint author), NIH, Off Res Womens Hlth, 6707 Democracy Blvd, Bethesda, MD 20817 USA.
EM janine.clayton@nih.gov
NR 5
TC 6
Z9 6
U1 0
U2 0
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 NOV 8
PY 2016
VL 316
IS 18
BP 1863
EP 1864
DI 10.1001/jama.2016.16405
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA EB1MN
UT WOS:000387116500008
PM 27802482
ER
PT J
AU Geng, S
Chen, KQ
Yuan, RX
Peng, L
Maitra, U
Diao, N
Chen, C
Zhang, Y
Hu, Y
Qi, CF
Pierce, S
Ling, WH
Xiong, HB
Li, LW
AF Geng, Shuo
Chen, Keqiang
Yuan, Ruoxi
Peng, Liang
Maitra, Urmila
Diao, Na
Chen, Chun
Zhang, Yao
Hu, Yuan
Qi, Chen-Feng
Pierce, Susan
Ling, Wenhua
Xiong, Huabao
Li, Liwu
TI The persistence of low-grade inflammatory monocytes contributes to
aggravated atherosclerosis
SO NATURE COMMUNICATIONS
LA English
DT Article
ID BREAST-CANCER CELLS; LOW-DOSE ENDOTOXIN; IRAK-M EXPRESSION; B TYPE-I;
UP-REGULATION; LIPOPOLYSACCHARIDE LPS; KAPPA-B; MACROPHAGES; TOLERANCE;
RECEPTOR
AB Sustained low-grade inflammation mediated by non-resolving inflammatory monocytes has long been suspected in the pathogenesis of atherosclerosis; however, the molecular mechanisms responsible for the sustainment of non-resolving inflammatory monocytes during atherosclerosis are poorly understood. Here we observe that subclinical endotoxemia, often seen in humans with chronic inflammation, aggravates murine atherosclerosis through programming monocytes into a non-resolving inflammatory state with elevated Ly6C, CCR5, MCP-1 and reduced SR-B1. The sustainment of inflammatory monocytes is due to the disruption of homeostatic tolerance through the elevation of miR-24 and reduction of the key negative-feedback regulator IRAK-M. miR-24 reduces the levels of Smad4 required for the expression of IRAK-M and also downregulates key lipid-processing molecule SR-B1. IRAK-M deficiency in turn leads to elevated miR-24 levels, sustains disruption of monocyte homeostasis and aggravates atherosclerosis. Our data define an integrated feedback circuit in monocytes and its disruption may lead to non-resolving low-grade inflammation conducive to atherosclerosis.
C1 [Geng, Shuo; Chen, Keqiang; Yuan, Ruoxi; Maitra, Urmila; Diao, Na; Chen, Chun; Zhang, Yao; Li, Liwu] Virginia Tech, Dept Biol Sci, Blacksburg, VA 24061 USA.
[Peng, Liang; Hu, Yuan; Xiong, Huabao] Icahn Sch Med Mt Sinai, Dept Med, Inst Immunol, New York, NY 10029 USA.
[Qi, Chen-Feng; Pierce, Susan] NIAID, Immunogenet Lab, NIH, Bethesda, MD 20892 USA.
[Ling, Wenhua] Sun Yat Sen Univ, Sch Publ Hlth, Guangzhou 510080, Guangdong, Peoples R China.
RP Li, LW (reprint author), Virginia Tech, Dept Biol Sci, Blacksburg, VA 24061 USA.; Xiong, HB (reprint author), Icahn Sch Med Mt Sinai, Dept Med, Inst Immunol, New York, NY 10029 USA.
EM Huabao.Xiong@mssm.edu; lwli@vt.edu
OI Li, Liwu/0000-0001-8870-5299
FU National Institute of Health grants [R01 HL115835, R56AI108264, RO1
AI104688, R56AI091871]; American Heart Association Award
[15POST25860003]
FX This work was supported by the National Institute of Health grants R01
HL115835, R56AI108264 to L.L., RO1 AI104688 and R56AI091871 to H.X., and
American Heart Association Award 15POST25860003 to S.G.
NR 68
TC 0
Z9 0
U1 5
U2 5
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2041-1723
J9 NAT COMMUN
JI Nat. Commun.
PD NOV 8
PY 2016
VL 7
AR 13436
DI 10.1038/ncomms13436
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EB3JJ
UT WOS:000387260200001
PM 27824038
ER
PT J
AU Permuth, JB
Reid, B
Earp, M
Chen, YA
Monteiro, ANA
Chen, ZH
Chenevix-Trench, G
Fasching, PA
Beckmann, MW
Lambrechts, D
Vanderstichele, A
Van Niewenhuyse, E
Vergote, I
Rossing, MA
Doherty, JA
Chang-Claude, J
Moysich, K
Odunsi, K
Goodman, MT
Shvetsov, YB
Wilkens, LR
Thompson, PJ
Dork, T
Bogdanova, N
Butzow, R
Nevanlinna, H
Pelttari, L
Leminen, A
Modugno, F
Edwards, RP
Ness, RB
Kelley, J
Heitz, F
Karlan, B
Lester, J
Kjaer, SK
Jensen, A
Giles, G
Hildebrandt, M
Liang, D
Lu, KH
Wu, XF
Levine, DA
Bisogna, M
Berchuck, A
Cramer, DW
Terry, KL
Tworoger, SS
Poole, EM
Bandera, EV
Fridley, B
Cunningham, J
Winham, SJ
Olson, SH
Orlow, I
Bjorge, L
Kiemeney, LA
Massuger, L
Pejovic, T
Moffitt, M
Le, N
Cook, LS
Brooks-Wilson, A
Kelemen, LE
Gronwald, J
Lubinski, J
Wentzensen, N
Brinton, LA
Lissowska, J
Yang, HN
Hogdall, E
Hogdall, C
Lundvall, L
Pharoah, PDP
Song, HL
Campbell, I
Eccles, D
McNeish, I
Whittemore, A
McGuire, V
Sieh, W
Rothstein, J
Phelan, CM
Risch, H
Narod, S
McLaughlin, J
Anton-Culver, H
Ziogas, A
Menon, U
Gayther, S
Ramus, SJ
Gentry-Maharaj, A
Pearce, CL
Wu, AH
Kupryjanczyk, J
Dansonka-Mieszkowska, A
Schildkraut, JM
Cheng, JQ
Goode, EL
Sellers, TA
AF Permuth, Jennifer B.
Reid, Brett
Earp, Madalene
Chen, Y. Ann
Monteiro, Alvaro N. A.
Chen, Zhihua
Chenevix-Trench, Georgia
Fasching, Peter A.
Beckmann, Matthias W.
Lambrechts, Diether
Vanderstichele, Adriaan
Van Niewenhuyse, Els
Vergote, Ignace
Rossing, Mary Anne
Doherty, Jennifer Anne
Chang-Claude, Jenny
Moysich, Kirsten
Odunsi, Kunle
Goodman, Marc T.
Shvetsov, Yurii B.
Wilkens, Lynne R.
Thompson, Pamela J.
Doerk, Thilo
Bogdanova, Natalia
Butzow, Ralf
Nevanlinna, Heli
Pelttari, Liisa
Leminen, Arto
Modugno, Francesmary
Edwards, Robert P.
Ness, Roberta B.
Kelley, Joseph
Heitz, Florian
Karlan, Beth
Lester, Jenny
Kjaer, Susanne K.
Jensen, Allan
Giles, Graham
Hildebrandt, Michelle
Liang, Dong
Lu, Karen H.
Wu, Xifeng
Levine, Douglas A.
Bisogna, Maria
Berchuck, Andrew
Cramer, Daniel W.
Terry, Kathryn L.
Tworoger, Shelley S.
Poole, Elizabeth M.
Bandera, Elisa V.
Fridley, Brooke
Cunningham, Julie
Winham, Stacey J.
Olson, Sara H.
Orlow, Irene
Bjorge, Line
Kiemeney, Lambertus A.
Massuger, Leon
Pejovic, Tanja
Moffitt, Melissa
Le, Nhu
Cook, Linda S.
Brooks-Wilson, Angela
Kelemen, Linda E.
Gronwald, Jacek
Lubinski, Jan
Wentzensen, Nicolas
Brinton, Louise A.
Lissowska, Jolanta
Yang, Hanna
Hogdall, Estrid
Hogdall, Claus
Lundvall, Lene
Pharoah, Paul D. P.
Song, Honglin
Campbell, Ian
Eccles, Diana
McNeish, Iain
Whittemore, Alice
McGuire, Valerie
Sieh, Weiva
Rothstein, Joseph
Phelan, Catherine M.
Risch, Harvey
Narod, Steven
McLaughlin, John
Anton-Culver, Hoda
Ziogas, Argyrios
Menon, Usha
Gayther, Simon
Ramus, Susan J.
Gentry-Maharaj, Aleksandra
Pearce, Celeste Leigh
Wu, Anna H.
Kupryjanczyk, Jolanta
Dansonka-Mieszkowska, Agnieszka
Schildkraut, Joellen M.
Cheng, Jin Q.
Goode, Ellen L.
Sellers, Thomas A.
CA AOCS Study Grp
TI Inherited variants affecting RNA editing may contribute to ovarian
cancer susceptibility: results from a large-scale collaboration
SO ONCOTARGET
LA English
DT Article
DE polymorphisms; RNA editing; ovarian cancer risk
ID GENOME-WIDE ASSOCIATION; GENOTYPE IMPUTATION; ADENOSINE-DEAMINASE;
ANALYSES REVEAL; LOCI; DISEASE; GENES; RARE
AB RNA editing in mammals is a form of post-transcriptional modification in which adenosine is converted to inosine by the adenosine deaminases acting on RNA (ADAR) family of enzymes. Based on evidence of altered ADAR expression in epithelial ovarian cancers (EOC), we hypothesized that single nucleotide polymorphisms (SNPs) in ADAR genes modify EOC susceptibility, potentially by altering ovarian tissue gene expression. Using directly genotyped and imputed data from 10,891 invasive EOC cases and 21,693 controls, we evaluated the associations of 5,303 SNPs in ADAD1, ADAR, ADAR2, ADAR3, and SND1. Unconditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI), with adjustment for European ancestry. We conducted gene-level analyses using the Admixture Maximum Likelihood (AML) test and the Sequence-Kernel Association test for common and rare variants (SKAT-CR). Association analysis revealed top risk-associated SNP rs77027562 (OR (95% CI)= 1.39 (1.17-1.64), P = 1.0x10(-4)) in ADAR3 and rs185455523 in SND1 (OR (95% CI) = 0.68 (0.56-0.83), P = 2.0x10(-4)). When restricting to serous histology (n = 6,500), the magnitude of association strengthened for rs185455523 (OR = 0.60, P = 1.0x10(-4)). Gene-level analyses revealed that variation in ADAR was associated (P < 0.05) with EOC susceptibility, with P-AML = 0.022 and PSKAT-CR = 0.020. Expression quantitative trait locus analysis in EOC tissue revealed significant associations (P < 0.05) with ADAR expression for several SNPs in ADAR, including rs1127313 (G/A), a SNP in the 3' untranslated region. In summary, germline variation involving RNA editing genes may influence EOC susceptibility, warranting further investigation of inherited and acquired alterations affecting RNA editing.
C1 [Permuth, Jennifer B.; Reid, Brett; Monteiro, Alvaro N. A.; Phelan, Catherine M.; Sellers, Thomas A.] H Lee Moffitt Canc Ctr & Res Inst, Dept Canc Epidemiol, Tampa, FL 33612 USA.
[Earp, Madalene; Cunningham, Julie; Winham, Stacey J.; Goode, Ellen L.] Mayo Clin, Div Epidemiol, Dept Hlth Sci Res, Rochester, MN USA.
[Chen, Y. Ann; Chen, Zhihua] H Lee Moffitt Canc Ctr & Res Inst, Dept Biostat & Bioinformat, Tampa, FL USA.
[Chenevix-Trench, Georgia] QIMR Berghofer Med Res Inst, Genet & Computat Biol Dept, Brisbane, Qld, Australia.
[Campbell, Ian; AOCS Study Grp] Peter MacCallum Canc Ctr, Div Res, Canc Genet Lab, Melbourne, Australia.
[Fasching, Peter A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Hematol & Oncol, Los Angeles, CA 90095 USA.
[Fasching, Peter A.; Beckmann, Matthias W.] Friedrich Alexander Univers Erlangen Nuremberg, Univ Hosp Erlangen, Dept Gynecol & Obstet, Ctr Comprehens Canc, Erlangen, Germany.
[Lambrechts, Diether] VIB, Vesalius Res Ctr, Leuven, Belgium.
[Lambrechts, Diether] Univ Leuven, Dept Oncol, Lab Translat Genet, Leuven, Belgium.
[Vanderstichele, Adriaan; Van Niewenhuyse, Els; Vergote, Ignace] Univ Hosp Leuven, Div Gynecol Oncol, Dept Obstet & Gynaecol, Leuven, Belgium.
[Vanderstichele, Adriaan; Van Niewenhuyse, Els; Vergote, Ignace] Univ Hosp Leuven, Leuven Canc Inst, Leuven, Belgium.
[Rossing, Mary Anne] Fred Hutchinson Canc Res Ctr, Program Epidemiol, Div Publ Hlth Sci, Seattle, WA 98104 USA.
[Rossing, Mary Anne] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
[Doherty, Jennifer Anne] Dartmouth Coll, Geisel Sch Med, Dept Epidemiol, Hanover, NY USA.
[Chang-Claude, Jenny] German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany.
[Chang-Claude, Jenny] Univ Med Ctr Hamburg Eppendorf, UCCH, Hamburg, Germany.
[Moysich, Kirsten] Roswell Pk Canc Inst, Dept Canc Prevent & Control, Buffalo, NY 14263 USA.
[Odunsi, Kunle] Roswell Pk Canc Inst, Dept Gynecol Oncol, Buffalo, NY 14263 USA.
[Goodman, Marc T.; Thompson, Pamela J.] Cedars Sinai Med Ctr, Canc Prevent & Control, Samuel Oshin Comprehens Canc Inst, Los Angeles, CA 90048 USA.
[Goodman, Marc T.; Thompson, Pamela J.] Cedars Sinai Med Ctr, Dept Biomed Sci, Community & Populat Hlth Res Inst, Los Angeles, CA 90048 USA.
[Shvetsov, Yurii B.; Wilkens, Lynne R.] Univ Hawaii, Ctr Canc, Canc Epidemiol Program, Honolulu, HI USA.
[Doerk, Thilo] Hannover Med Sch, Gynaecol Res Unit, Hannover, Germany.
[Bogdanova, Natalia] Hannover Med Sch, Radiaton Oncol Res Unit, Hannover, Germany.
[Butzow, Ralf] Univ Helsinki, Dept Pathol, Helsinki, Finland.
[Butzow, Ralf] Helsinki Univ Hosp, Helsinki, Finland.
[Nevanlinna, Heli; Pelttari, Liisa; Leminen, Arto] Univ Helsinki, Dept Obstet & Gynecol, Helsinki, Finland.
[Nevanlinna, Heli; Pelttari, Liisa; Leminen, Arto] Univ Helsinki, Cent Hosp, Helsinki, Finland.
[Modugno, Francesmary; Edwards, Robert P.; Kelley, Joseph] Univ Pittsburgh, Sch Med, Dept Obstet Gynecol & Reprod Sci, Div Gynecol Oncol, Pittsburgh, PA USA.
[Modugno, Francesmary; Edwards, Robert P.] Magee Womens Res Inst, Ovarian Canc Ctr Excellence, Womens Canc Res Program, Pittsburgh, PA USA.
[Modugno, Francesmary; Edwards, Robert P.] Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA.
[Modugno, Francesmary] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA.
[Ness, Roberta B.] Univ Texas Houston, Sch Publ Hlth, Houston, TX USA.
[Heitz, Florian] Knappschaft GmbH, Evang Huyssens Stiftung, Kliniken Essen Mitte, Dept Gynecol & Gynecol Oncol, Essen, Germany.
[Heitz, Florian] Dr Horst Schmidt Klin Wiesbaden, Dept Gynecol & Gynecol Oncol, Wiesbaden, Germany.
[Karlan, Beth; Lester, Jenny] Cedars Sinai Med Ctr, Womens Canc Program, Samuel Oschin Comprehens Canc Inst, Los Angeles, CA 90048 USA.
[Kjaer, Susanne K.; Jensen, Allan; Hogdall, Estrid] Danish Canc Soc, Res Ctr, Dept Virus Lifestyle & Genes, Copenhagen, Denmark.
[Kjaer, Susanne K.] Univ Copenhagen, Dept Gynaecol, Rigshosp, Copenhagen, Denmark.
[Giles, Graham] Canc Epidemiol Ctr, Melbourne, Vic, Australia.
[Giles, Graham] Univ Melbourne, Ctr Epidemiol & Biostat, Melbourne, Vic 3010, Australia.
[Giles, Graham] Monash Univ, Dept Epidemiol & Prevent Med, Melbourne, Vic, Australia.
[Hildebrandt, Michelle; Wu, Xifeng] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA.
[Liang, Dong] Texas Southern Univ, Coll Pharm & Hlth Sci, Houston, TX USA.
[Lu, Karen H.] Univ Texas MD Anderson Canc Ctr, Dept Gynecol Oncol, Houston, TX 77030 USA.
[Levine, Douglas A.; Bisogna, Maria] Mem Sloan Kettering Canc Ctr, Dept Surg, Gynecol Serv, New York, NY 10021 USA.
[Berchuck, Andrew] Duke Univ, Med Ctr, Dept Obstet & Gynecol, Durham, NC 27710 USA.
[Cramer, Daniel W.; Terry, Kathryn L.] Brigham & Womens Hosp, Obstet & Gynecol Epidemiol Ctr, 75 Francis St, Boston, MA 02115 USA.
[Cramer, Daniel W.; Terry, Kathryn L.; Tworoger, Shelley S.] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.
[Tworoger, Shelley S.; Poole, Elizabeth M.] Brigham & Womens Hosp, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA.
[Tworoger, Shelley S.; Poole, Elizabeth M.] Harvard Med Sch, Boston, MA USA.
[Bandera, Elisa V.] Rutgers Canc Inst New Jersey, Canc Prevent & Control Program, New Brunswick, NJ USA.
[Fridley, Brooke] Univ Kansas, Med Ctr, Dept Biostat, Kansas City, KS 66103 USA.
[Olson, Sara H.; Orlow, Irene] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, 1275 York Ave, New York, NY 10021 USA.
[Bjorge, Line] Univ Bergen, Ctr Canc Biomarkers, Dept Clin Sci, Bergen, Norway.
[Bjorge, Line] Haukeland Hosp, Dept Gynecol & Obstet, Bergen, Norway.
[Kiemeney, Lambertus A.] Radboud Univ Nijmegen, Med Ctr, Radboud Inst Hlth Sci, Nijmegen, Netherlands.
[Massuger, Leon] Radboud Univ Nijmegen, Med Ctr, Radboud Inst Mol Life Sci, Dept Gynaecol, Nijmegen, Netherlands.
[Pejovic, Tanja; Moffitt, Melissa] Oregon Hlth & Sci Univ, Dept Obstet & Gynecol, Portland, OR 97201 USA.
[Pejovic, Tanja; Moffitt, Melissa] Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97201 USA.
[Le, Nhu] BC Canc Agcy, Canc Control Res, Vancouver, BC, Canada.
[Cook, Linda S.] Univ New Mexico, Dept Internal Med, Div Epidemiol & Biostat, Albuquerque, NM 87131 USA.
[Brooks-Wilson, Angela] BC Canc Agcy, Canadas Michael Smith Genome Sci Ctr, Vancouver, BC, Canada.
[Brooks-Wilson, Angela] Simon Fraser Univ, Dept Biomed Physiol & Kinesiol, Burnaby, BC, Canada.
[Kelemen, Linda E.] Med Univ South Carolina, Coll Med, Dept Publ Hlth Sci, Charleston, SC USA.
[Gronwald, Jacek; Lubinski, Jan] Pomeranian Med Univ, Int Hereditary Canc Ctr, Dept Genet & Pathol, Szczecin, Poland.
[Wentzensen, Nicolas; Brinton, Louise A.; Yang, Hanna] NCI, Div Canc Epidemiol & Genet, Bethesda, MD USA.
[Lissowska, Jolanta] Maria Sklodowska Curie Mem Canc Ctr, Dept Canc Epidemiol & Prevent, Warsaw, Poland.
[Hogdall, Claus; Lundvall, Lene] Rigshosp, Dept Obstet & Gynecol, Juliane Marie Ctr, Copenhagen, Denmark.
[Pharoah, Paul D. P.] Univ Cambridge, Strangeways Res Lab, Dept Publ Hlth & Primary Care, Cambridge, England.
[Pharoah, Paul D. P.; Song, Honglin] Univ Cambridge, Strangeways Res Lab, Dept Oncol, Cambridge, England.
[Campbell, Ian] Univ Melbourne, Dept Pathol, Parkville, Vic, Australia.
[Eccles, Diana] Univ Southampton, Fac Med, Southampton Univ Hosp, Southampton, Hants, England.
[McNeish, Iain] Unvers Glasgow, Inst Canc Sci, Wolfson Wohl Canc Res Ctr, Beatson Inst Canc Res, Glasgow, Lanark, Scotland.
[Whittemore, Alice; McGuire, Valerie; Sieh, Weiva; Rothstein, Joseph] Stanford Univ, Sch Med, Dept Hlth Res & Policy Epidemiol, Stanford, CA USA.
[Risch, Harvey; Menon, Usha] Yale Sch Publ Hlth, Dept Chron Dis Epidemiol, New Haven, CT USA.
[Narod, Steven] Univ Toronto, Womens Coll Res Inst, Toronto, ON, Canada.
[McLaughlin, John] Publ Hlth Ontario, Toronto, ON, Canada.
[Anton-Culver, Hoda] Univ Calif Irvine, Dept Epidemiol, Genet Epidemiol Res Inst, UCI Sch Med, Irvine, CA USA.
[Ziogas, Argyrios] Univ Calif Irvine, Dept Epidemiol, Irvine, CA USA.
[Gayther, Simon; Ramus, Susan J.; Pearce, Celeste Leigh; Wu, Anna H.] Univ Southern Calif, Norris Comprehens Canc Ctr, Dept Prevent Med, Keck Sch Med, Los Angeles, CA USA.
[Gentry-Maharaj, Aleksandra] UCL, Inst Womens Hlth, Womens Canc, London, England.
[Pearce, Celeste Leigh] Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA.
[Kupryjanczyk, Jolanta; Dansonka-Mieszkowska, Agnieszka] Maria Sklodowska Curie Mem Canc Ctr & Inst Oncol, Dept Pathol & Lab Diagnost, Warsaw, Poland.
[Schildkraut, Joellen M.] Duke Univ, Med Ctr, Dept Community & Family Med, Durham, NC 27710 USA.
[Schildkraut, Joellen M.] Duke Canc Inst, Canc Control & Populat Sci, Durham, NC USA.
[Cheng, Jin Q.] H Lee Moffitt Canc Ctr & Res Inst, Dept Mol Oncol, Tampa, FL USA.
[Sellers, Thomas A.] Ovarian Canc Assoc Consortium, New York, NY USA.
RP Permuth, JB (reprint author), H Lee Moffitt Canc Ctr & Res Inst, Dept Canc Epidemiol, Tampa, FL 33612 USA.
EM jenny.permuth@moffitt.org
RI Gronwald, Jacek/A-4576-2017; Bjorge, Line/C-1307-2017; Brooks-Wilson,
Angela/E-9399-2012; Dork, Thilo/J-8620-2012;
OI Gronwald, Jacek/0000-0002-3643-2871; Bjorge, Line/0000-0002-0240-2770;
Brooks-Wilson, Angela/0000-0003-1009-6408; Winham,
Stacey/0000-0002-8492-9102
FU US National Institute of Health [R01-CA-11343, R01-CA114343-S1]; Genetic
Associations and Mechanisms in Oncology (GAME-ON), a NCI Cancer
Post-GWAS Initiative [U19-CA148112]; NHMRC; Medical Research Council;
University of Erlangen-Nuremberg; Programme of Clinical Biomedical
Research [01 GB 9401]; Helsinki University Research Fund; NIH/National
Center for Research Resources/General Clinical Research Center
[M01-RR000056, R01-CA126841]; National Center for Advancing
Translational Sciences (NCATS) [UL1TR000124]; National Cancer Institute,
Bethesda, MD [R01-CA61107]; Danish Cancer Society, Copenhagen, Denmark
[94 222 52]; Mermaid I project; VicHealth; Cancer Council Victoria;
Australian NHMRC [209057, 251553, 504711]; DOD Ovarian Cancer Research
Program [W81XWH-07-0449]; NCI CCSG award [P30-CA008748]; Canadian
Institutes of Health Research [MOP-86727]; NIH/NCI [1 R01CA160669-01A1];
NIH [R01 CA063678, CA063682, CA149429]; Lon V Smith Foundation
[VLS-39420]; Eve Appeal (The Oak Foundation); National Institute for
Health Research University College London Hospitals Biomedical Research
Centre; California Cancer Research Program [00-01389V-20170, 2II0200];
Biostatistics and Cancer Informatics Core Facilities at the H. Lee
Moffitt Cancer Center & Research Institute, an NCI designated
Comprehensive Cancer Center [P30-CA076292]
FX Funding for this study was supported in part by the US National
Institute of Health (R01-CA-11343 and R01-CA114343-S1) and the Genetic
Associations and Mechanisms in Oncology (GAME-ON), a NCI Cancer
Post-GWAS Initiative (U19-CA148112). In addition, we acknowledge the
following: AUS: U.S. Army Medical Research and Materiel Command
(DAMD17-01-1-0729), National Health & Medical Research Council of
Australia, Cancer Councils of New South Wales, Victoria, Queensland,
South Australia and Tasmania, Cancer Foundation of Western Australia;
National Health and Medical Research Council of Australia (199600 and
400281). The Australian Ovarian Cancer Study Management Group (D.
Bowtell, G. Chenevix-Trench, A. deFazio, D. Gertig, A. Green, P. Webb)
and ACS Investigators (A. Green, P. Parsons, N. Hayward, P. Webb, D.
Whiteman) thank all the clinical and scientific collaborators (see
http://www.aocstudy.org/) and the women for their contribution. GCT & PW
are supported by Fellowships from NHMRC; AP is funded by a Medical
Research Council studentship; BAV: ELAN funds of the University of
Erlangen-Nuremberg. BEL: Nationaal Kankerplan, we would like to thank
Gilian Peuteman, Thomas Van Brussel, Annick Van den Broeck and Joke De
Roover for technical assistance; DOV: U.S. National Institutes of Health
R01-CA112523 and R01-CA87538; GER: German Federal Ministry of Education
and Research, Programme of Clinical Biomedical Research (01 GB 9401) and
the German Cancer Research Center (DKFZ). GRR: Roswell Park Cancer
Institute Alliance Foundation, P30 CA016056. HAW: U.S. National
Institutes of Health (R01-CA58598, N01-CN-55424 and N01-PC-67001); HJO
and HMO: Intramural funding; Rudolf-Bartling Foundation; HOC: Helsinki
University Research Fund; HOP: DOD DAMD17-02-1-0669 and NCI
K07-CA080668, R01-CA95023, P50-CA159981; NIH/National Center for
Research Resources/General Clinical Research Center grant M01-RR000056;
R01-CA126841; LAX: American Cancer Society Early Detection Professorship
(SIOP-06-258-01-COUN) and the National Center for Advancing
Translational Sciences (NCATS), Grant UL1TR000124; MAL: Funding for this
study was provided by research grant R01-CA61107 from the National
Cancer Institute, Bethesda, MD; research grant 94 222 52 from the Danish
Cancer Society, Copenhagen, Denmark; and the Mermaid I project.; MAY:
National Institutes of Health (R01-CA122443, P30-CA15083, P50-CA136393),
Mayo Foundation; Minnesota Ovarian Cancer Alliance; Fred C. and
Katherine B. Andersen Foundation; MCC: MCCS cohort recruitment was
funded by VicHealth and Cancer Council Victoria. The MCCS was further
supported by Australian NHMRC grants 209057, 251553 and 504711 and by
infrastructure provided by Cancer Council Victoria. Cases and their
vital status were ascertained through the Victorian Cancer Registry
(VCR) and the Australian Institute of Health and Welfare (AIHW),
including the National Death Index and the Australian Cancer Database;;
MDA: DOD Ovarian Cancer Research Program (W81XWH-07-0449); NEC: National
Institutes of Health R01-CA54419 and P50-CA105009 and Department of
Defense W81XWH-10-1-02802; NHS: National Institute of Health
(UM1-CA176726, and R01-CA67262).; The NHS would like to thank the
participants and staff for their valuable contributions as well as the
following state cancer registries for their help: AL, AZ, AR, CA, CO,
CT, DE, FL, GA, ID, IL, IN, IA, KY, LA, ME, MD, MA, MI, NE, NH, NJ, NY,
NC, ND, OH, OK, OR, PA, RI, SC, TN, TX, VA, WA, WY; NJO: National Cancer
Institute (NIH-K07 CA095666, R01-CA83918, NIH-K22-CA138563, and
P30-CA072720) and the Cancer Institute of New Jersey, and NCI CCSG award
(P30-CA008748); NOR: Helse Vest, The Norwegian Cancer Society, The
Research Council of Norway; NTH: Radboud University Medical Centre; ORE:
OHSU Foundation; OVA: This work was supported by Canadian Institutes of
Health Research grant (MOP-86727) and by NIH/NCI 1 R01CA160669-01A1;
POC: Pomeranian Medical University; POL: Intramural Research Program of
the NCI; PVD: Herlev Hospitals Forskningsrad, Direktor Jacob Madsens og
Hustru Olga Madsens fond, Arvid Nilssons fond, Gangsted fonden, Herlev
Hospitals Forskningsrad and Danish Cancer Society; RMH: Cancer Research
UK (no grant number is available); SEA: Cancer Research UK (C490/A10119
C490/A10124); UK National Institute for Health Research Biomedical
Research Centres at the University of Cambridge, SEARCH team, Craig
Luccarini, Caroline Baynes, Don Conroy; SRO: Cancer Research UK
(C536/A13086, C536/A6689) and Imperial Experimental Cancer Research
Centre (C1312/A15589) and to thank all members of Scottish
Gynaecological Clinical Trials group and COTROC1 investigators; STA: US
National Institutes of Health U01-CA71966, R01-CA16056, K07-CA143047,
and U01-CA69417 for recruitment of controls by the Cancer Prevention
Institute of California; TOR: NIH grants R01 CA063678, CA063682, and
CA149429; UCI: NIH R01-CA058860, and the Lon V Smith Foundation grant
VLS-39420; UKO: The UKOPS study was funded by The Eve Appeal (The Oak
Foundation) and supported by the National Institute for Health Research
University College London Hospitals Biomedical Research Centre. We
particularly thank I. Jacobs, M. Widschwendter, E. Wozniak, A. Ryan, J.
Ford and N. Balogun for their contribution to the study; UKR: Cancer
Research UK (C490/A6187); UK National Institute for Health Research
Biomedical Research Centres at the University of Cambridge; USC:
P01-CA17054, P30-CA14089, R01-CA61132, N01-PC67010, R03-CA113148,
R03-CA115195, N01-CN025403, and California Cancer Research Program
(00-01389V-20170, 2II0200). WOC: National Science Centren (N N301 5645
40) The Maria Sklodowska-Curie Memorial Cancer Center and Institute of
Oncology, Warsaw, Poland. This study was supported in part by the
Biostatistics and Cancer Informatics Core Facilities at the H. Lee
Moffitt Cancer Center & Research Institute, an NCI designated
Comprehensive Cancer Center (P30-CA076292).
NR 28
TC 1
Z9 1
U1 7
U2 7
PU IMPACT JOURNALS LLC
PI ALBANY
PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA
SN 1949-2553
J9 ONCOTARGET
JI Oncotarget
PD NOV 8
PY 2016
VL 7
IS 45
BP 72381
EP 72394
DI 10.18632/oncotarget.10546
PG 14
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA EB5WT
UT WOS:000387452100001
PM 27911851
ER
PT J
AU Sun, Y
Zhang, HM
Kazemian, M
Troy, JM
Seward, C
Lu, XC
Stubbs, L
AF Sun, Younguk
Zhang, Huimin
Kazemian, Majid
Troy, Joseph M.
Seward, Christopher
Lu, Xiaochen
Stubbs, Lisa
TI ZSCAN5B and primate-specific paralogs bind RNA polymerase III genes and
extra-TFIIIC (ETC) sites to modulate mitotic progression
SO ONCOTARGET
LA English
DT Article
DE zinc finger transcription factor; primate-specific duplication; RNA
Polymerase III transcription; chromatin architecture; cell cycle
ID CARTILAGE-HAIR HYPOPLASIA; POL-II; SACCHAROMYCES-CEREVISIAE;
MESSENGER-RNA; HUMAN GENOME; HUMAN-CELLS; TRANSCRIPTION; EXPRESSION;
CHROMATIN; PROMOTERS
AB Mammalian genomes contain hundreds of genes transcribed by RNA Polymerase III (Pol III), encoding noncoding RNAs and especially the tRNAs specialized to carry specific amino acids to the ribosome for protein synthesis. In addition to this well-known function, tRNAs and their genes (tDNAs) serve a variety of other critical cellular functions. For example, tRNAs and other Pol III transcripts can be cleaved to yield small RNAs with potent regulatory activities. Furthermore, from yeast to mammals, active tDNAs and related "extra-TFIIIC" (ETC) loci provide the DNA scaffolds for the most ancient known mechanism of three-dimensional chromatin architecture. Here we identify the ZSCAN5 TF family - including mammalian ZSCAN5B and its primate-specific paralogs - as proteins that occupy mammalian Pol III promoters and ETC sites. We show that ZSCAN5B binds with high specificity to a conserved subset of Pol III genes in human and mouse. Furthermore, primate-specific ZSCAN5A and ZSCAN5D also bind Pol III genes, although ZSCAN5D preferentially localizes to MIR SINE-and LINE2-associated ETC sites. ZSCAN5 genes are expressed in proliferating cell populations and are cell-cycle regulated, and siRNA knockdown experiments suggested a cooperative role in regulation of mitotic progression. Consistent with this prediction, ZSCAN5A knockdown led to increasing numbers of cells in mitosis and the appearance of cells. Together, these data implicate the role of ZSCAN5 genes in regulation of Pol III genes and nearby Pol II Ioci, ultimately influencing cell cycle progression and differentiation in a variety of tissues.
C1 [Sun, Younguk; Zhang, Huimin; Kazemian, Majid; Troy, Joseph M.; Seward, Christopher; Lu, Xiaochen; Stubbs, Lisa] Univ Illinois, Inst Genom Biol, Urbana, IL 61801 USA.
[Sun, Younguk; Zhang, Huimin; Seward, Christopher; Lu, Xiaochen; Stubbs, Lisa] Univ Illinois, Dept Cell & Dev Biol, Urbana, IL 61801 USA.
[Troy, Joseph M.] Univ Illinois, Illinois Informat Program, Urbana, IL USA.
[Kazemian, Majid] NHLBI, Lab Mol Immunol, NIH, Bldg 10, Bethesda, MD 20892 USA.
[Kazemian, Majid] NHLBI, Ctr Immunol, NIH, Bldg 10, Bethesda, MD 20892 USA.
RP Stubbs, L (reprint author), Univ Illinois, Inst Genom Biol, Urbana, IL 61801 USA.; Stubbs, L (reprint author), Univ Illinois, Dept Cell & Dev Biol, Urbana, IL 61801 USA.
EM ljstubbs@illinois.edu
OI Stubbs, Lisa/0000-0002-9556-1972; Kazemian, Majid/0000-0001-7080-8820
FU March of Dimes Foundation [FY2011-393]; National Institutes of General
Medical Sciences [R01-GM078368]
FX This work was supported by March of Dimes Foundation, grant FY2011-393,
and by the National Institutes of General Medical Sciences grants
R01-GM078368 (awarded to L.S.).
NR 68
TC 0
Z9 0
U1 3
U2 3
PU IMPACT JOURNALS LLC
PI ORCHARD PARK
PA 6666 E QUAKER ST, STE 1, ORCHARD PARK, NY 14127 USA
SN 1949-2553
J9 ONCOTARGET
JI Oncotarget
PD NOV 8
PY 2016
VL 7
IS 45
BP 72571
EP 72592
DI 10.18632/oncotarget.12508
PG 22
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA EB5WT
UT WOS:000387452100015
PM 27732952
ER
PT J
AU Lin, H
Mueller-Nurasyid, M
Smith, AV
Arking, DE
Barnard, J
Bartz, TM
Lunetta, KL
Lohman, K
Kleber, ME
Lubitz, SA
Geelhoed, B
Trompet, S
Niemeijer, MN
Kacprowski, T
Chasman, DI
Klarin, D
Sinner, MF
Waldenberger, M
Meitinger, T
Harris, TB
Launer, LJ
Soliman, EZ
Chen, LY
Smith, JD
Van Wagoner, DR
Rotter, JI
Psaty, BM
Xie, Z
Hendricks, AE
Ding, J
Delgado, GE
Verweij, N
van der Harst, P
Macfarlane, PW
Ford, I
Hofman, A
Uitterlinden, A
Heeringa, J
Franco, OH
Kors, JA
Weiss, S
Volzke, H
Rose, LM
Natarajan, P
Kathiresan, S
Kaab, S
Gudnason, V
Alonso, A
Chung, MK
Heckbert, SR
Benjamin, EJ
Liu, Y
Marz, W
Rienstra, M
Jukema, JW
Stricker, BH
Dorr, M
Albert, CM
Ellinor, PT
AF Lin, Honghuang
Mueller-Nurasyid, Martina
Smith, Albert V.
Arking, Dan E.
Barnard, John
Bartz, Traci M.
Lunetta, Kathryn L.
Lohman, Kurt
Kleber, Marcus E.
Lubitz, Steven A.
Geelhoed, Bastiaan
Trompet, Stella
Niemeijer, Maartje N.
Kacprowski, Tim
Chasman, Daniel I.
Klarin, Derek
Sinner, Moritz F.
Waldenberger, Melanie
Meitinger, Thomas
Harris, Tamara B.
Launer, Lenore J.
Soliman, Elsayed Z.
Chen, Lin Y.
Smith, Jonathan D.
Van Wagoner, David R.
Rotter, Jerome I.
Psaty, Bruce M.
Xie, Zhijun
Hendricks, Audrey E.
Ding, Jingzhong
Delgado, Graciela E.
Verweij, Niek
van der Harst, Pim
Macfarlane, Peter W.
Ford, Ian
Hofman, Albert
Uitterlinden, Andre
Heeringa, Jan
Franco, Oscar H.
Kors, Jan A.
Weiss, Stefan
Volzke, Henry
Rose, Lynda M.
Natarajan, Pradeep
Kathiresan, Sekar
Kaab, Stefan
Gudnason, Vilmundur
Alonso, Alvaro
Chung, Mina K.
Heckbert, Susan R.
Benjamin, Emelia J.
Liu, Yongmei
Marz, Winfried
Rienstra, Michiel
Jukema, J. Wouter
Stricker, Bruno H.
Dorr, Marcus
Albert, Christine M.
Ellinor, Patrick T.
TI Gene-gene Interaction Analyses for Atrial Fibrillation
SO SCIENTIFIC REPORTS
LA English
DT Article
ID PROTEIN-INTERACTION MAPS; FAMILIAL AGGREGATION; MISSING HERITABILITY;
BREAST-CANCER; ASSOCIATION; RISK; VARIANTS; DISEASE; SUSCEPTIBILITY;
METAANALYSIS
AB Atrial fibrillation (AF) is a heritable disease that affects more than thirty million individuals worldwide. Extensive efforts have been devoted to the study of genetic determinants of AF. The objective of our study is to examine the effect of gene-gene interaction on AF susceptibility. We performed a large-scale association analysis of gene-gene interactions with AF in 8,173 AF cases, and 65,237 AF-free referents collected from 15 studies for discovery. We examined putative interactions between genome-wide SNPs and 17 known AF-related SNPs. The top interactions were then tested for association in an independent cohort for replication, which included more than 2,363 AF cases and 114,746 AF-free referents. One interaction, between rs7164883 at the HCN4 locus and rs4980345 at the SLC28A1 locus, was found to be significantly associated with AF in the discovery cohorts (interaction OR = 1.44, 95% CI: 1.27-1.65, P = 4.3 x 10(-8)). Eight additional gene-gene interactions were also marginally significant (P < 5 x 10(-7)). However, none of the top interactions were replicated. In summary, we did not find significant interactions that were associated with AF susceptibility. Future increases in sample size and denser genotyping might facilitate the identification of gene-gene interactions associated with AF.
C1 [Lin, Honghuang; Lunetta, Kathryn L.; Hendricks, Audrey E.; Benjamin, Emelia J.] NHLBI, Framingham, MA USA.
[Lin, Honghuang; Lunetta, Kathryn L.; Hendricks, Audrey E.; Benjamin, Emelia J.] Boston Univ, Framingham Heart Study, Framingham, MA USA.
[Lin, Honghuang; Xie, Zhijun] Boston Univ, Sch Med, Dept Med, Sect Computat Biomed, Boston, MA 02118 USA.
[Mueller-Nurasyid, Martina] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Genet Epidemiol, Neuherberg, Germany.
[Mueller-Nurasyid, Martina; Sinner, Moritz F.; Kaab, Stefan] Ludwig Maximilians Univ Munchen, Dept Med 1, Munich, Germany.
[Mueller-Nurasyid, Martina; Waldenberger, Melanie; Meitinger, Thomas; Kaab, Stefan] Partner Site Munich Heart Alliance, DZHK German Ctr Cardiovasc Res, Munich, Germany.
[Smith, Albert V.; Gudnason, Vilmundur] Iceland Heart Assoc, Kopavogur, Iceland.
[Smith, Albert V.; Gudnason, Vilmundur] Univ Iceland, Fac Med, Reykjavik, Iceland.
[Arking, Dan E.] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD USA.
[Barnard, John; Smith, Jonathan D.; Van Wagoner, David R.; Chung, Mina K.] Cleveland Clin, Cleveland, OH 44106 USA.
[Bartz, Traci M.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
[Lunetta, Kathryn L.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Lohman, Kurt] Wake Forest Sch Med, Publ Hlth Sci, Dept Biostat Sci, Winston Salem, NC USA.
[Kleber, Marcus E.; Waldenberger, Melanie; Delgado, Graciela E.] Heidelberg Univ, Med Fac Mannheim, Dept Med 5, Theodor Kutzer Ufer 1-3, D-68167 Mannheim, Germany.
[Lubitz, Steven A.] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA.
[Lubitz, Steven A.; Natarajan, Pradeep; Kathiresan, Sekar; Ellinor, Patrick T.] Harvard Med Sch, Boston, MA USA.
[Geelhoed, Bastiaan; Verweij, Niek; van der Harst, Pim; Rienstra, Michiel] Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, Groningen, Netherlands.
[Trompet, Stella; Jukema, J. Wouter] Leiden Univ, Med Ctr, Dept Cardiol, Leiden, Netherlands.
[Trompet, Stella] Leiden Univ, Med Ctr, Dept Gerontol & Geriatr, Leiden, Netherlands.
[Niemeijer, Maartje N.; Hofman, Albert; Heeringa, Jan; Franco, Oscar H.] Univ Med Ctr Rotterdam, Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.
[Kacprowski, Tim; Weiss, Stefan] Univ Med, Interfac Inst Genet & Funct Genom, Dept Funct Genom, Greifswald, Germany.
[Kacprowski, Tim; Weiss, Stefan] Ernst Moritz Arndt Univ Greifswald, Greifswald, Germany.
[Kacprowski, Tim; Weiss, Stefan; Volzke, Henry; Dorr, Marcus] Partner Site Greifswald, DZHK German Ctr Cardiovasc Res, Greifswald, Germany.
[Chasman, Daniel I.; Rose, Lynda M.; Albert, Christine M.] Brigham & Womens Hosp, Div Prevent Med, 75 Francis St, Boston, MA 02115 USA.
[Klarin, Derek; Natarajan, Pradeep; Kathiresan, Sekar] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.
[Klarin, Derek; Natarajan, Pradeep; Kathiresan, Sekar] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Klarin, Derek] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA.
[Klarin, Derek; Natarajan, Pradeep; Kathiresan, Sekar] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA.
[Waldenberger, Melanie] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Res Unit Mol Epidemiol, Neuherberg, Germany.
[Meitinger, Thomas] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Human Genet, Neuherberg, Germany.
[Meitinger, Thomas] Tech Univ Munich, Inst Human Genet, Munich, Germany.
[Harris, Tamara B.; Launer, Lenore J.] NIA, NIH, Bethesda, MD 20892 USA.
[Soliman, Elsayed Z.] Wake Forest Sch Med, Epidemiol Cardiol Res Ctr, Winston Salem, NC USA.
[Chen, Lin Y.] Univ Minnesota, Sch Med, Dept Med, Cardiovasc Div, Minneapolis, MN 55455 USA.
[Rotter, Jerome I.] Harbor UCLA Med Ctr, LABioMed, Dept Pediat, Inst Translat Genom & Populat Sci JIR, Torrance, CA 90509 USA.
[Rotter, Jerome I.] Harbor UCLA Med Ctr, LABioMed, Dept Med, Inst Translat Genom & Populat Sci JIR, Torrance, CA 90509 USA.
[Psaty, Bruce M.] Univ Washington, Cardiovasc Hlth Res Unit, Dept Med, Seattle, WA USA.
[Psaty, Bruce M.] Univ Washington, Dept Epidemiol, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA.
[Psaty, Bruce M.] Univ Washington, Dept Hlth Serv, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA.
[Psaty, Bruce M.; Heckbert, Susan R.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA USA.
[Hendricks, Audrey E.] Univ Colorado, Math & Stat Sci, Denver, CO 80202 USA.
[Ding, Jingzhong] Wake Forest Sch Med, Dept Gerontol & Geriatr Med, Winston Salem, NC USA.
[Macfarlane, Peter W.] Univ Glasgow, Coll Vet Med & Life Sci, Inst Hlth & Wellbeing, Glasgow, Lanark, Scotland.
[Ford, Ian] Univ Glasgow, Robertson Ctr Biostat, Glasgow, Lanark, Scotland.
[Uitterlinden, Andre; Stricker, Bruno H.] Univ Med Ctr Rotterdam, Erasmus MC, Dept Epidemiol & Internal Med, Rotterdam, Netherlands.
[Kors, Jan A.] Univ Med Ctr Rotterdam, Erasmus MC, Dept Med Informat, Rotterdam, Netherlands.
[Volzke, Henry] Univ Med Greifswald, Inst Community Med, Greifswald, Germany.
[Alonso, Alvaro] Emory Univ, Rollins Sch Publ Hlth, Dept Epidemiol, Atlanta, GA 30322 USA.
[Heckbert, Susan R.] Univ Washington, Dept Epidemiol, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA.
[Benjamin, Emelia J.] Boston Univ, Sch Med, Dept Med, Sect Cardiovasc Med & Prevent Med, Boston, MA 02118 USA.
[Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.
[Liu, Yongmei] Wake Forest Sch Med, Publ Hlth Sci, Dept Epidemiol & Prevent, Winston Salem, NC USA.
[Marz, Winfried] Synlab Acad, Synlab Serv, GmbH P5,7, D-68161 Mannheim, Germany.
[Marz, Winfried] Med Univ Graz, Clin Inst Med & Chem Lab Diagnost, Graz, Austria.
[Marz, Winfried] Heidelberg Univ, Med Fac Mannheim, Med Clin Nephrol 5, Hypertensiol,Rheumatol,Endocrinol,Diabetol, Mannheim, Germany.
[Stricker, Bruno H.] Inspectorate Hlth Care, Utrecht, Netherlands.
[Dorr, Marcus] Univ Med Greifswald, Dept Internal Med B, Greifswald, Germany.
RP Lin, H (reprint author), NHLBI, Framingham, MA USA.; Lin, H (reprint author), Boston Univ, Framingham Heart Study, Framingham, MA USA.; Lin, H (reprint author), Boston Univ, Sch Med, Dept Med, Sect Computat Biomed, Boston, MA 02118 USA.
EM hhlin@bu.edu
RI Alonso, Alvaro/A-4917-2010; Verweij, Niek/A-4499-2017;
OI Alonso, Alvaro/0000-0002-2225-8323; Hendricks,
Audrey/0000-0002-7152-0287; Rienstra, Michiel/0000-0002-2581-070X
FU German Federal Ministry of Education and Research (BMBF); German
National Competence network on atrial fibrillation (AFNET); Leducq
Foundation [07-CVD 03]; D.W. Reynolds Foundation Clinical Cardiovascular
Research Center at Johns Hopkins University; Bioinformatics for the
Functional Analysis of Mammalian Genomes program (BFAM) [01GS0499,
01GI0204, 01GS0838]; Helmholtz Zentrum Munchen - German Research Center
for Environmental Health; State of Bavaria; Munich Center of Health
Sciences (MC-Health), Ludwig-Maximilians-Universitat; German Heart
Foundation; National Heart, Lung, and Blood Institute
[HHSN268201100005C, HHSN268201100006C, HHSN268201100007C,
HHSN268201100008C, HHSN268201100009C, HHSN268201100010C,
HHSN268201100011C, HHSN268201100012C, R01HL087641, R01HL59367,
R01HL086694]; National Human Genome Research Institute [U01HG004402];
National Institutes of Health [HHSN268200625226C, UL1RR025005]; American
Heart Association [16EIA26410001, 13EIA14220013]; NIH Roadmap for
Medical Research; NINDS; NIA [AG-023629, AG-15928, AG-20098, AG-027058];
NIH [R01HL090620, R01HL111314, 1RO1HL092577, 2R01LM010098, HL104156,
HL105780, HL065962, K23HL114724]; NIH/NCRR CTSA grant [1UL-RR024989];
Heart and Vascular Institute Philanthropic grant, Department of
Cardiovascular Medicine, Cleveland Clinic (Chung); Leducq Fondation
[07-CVD-03]; Boston University [N01-HC-25195, HHSN268201500001I];
Benjamin and Ellinor [1R01HL128914]; 7th Framework Program (AtheroRemo)
[201668, 305739]; Dutch Kidney Foundation [E0.13]; Netherlands
organization for health research and development [175.010.2007.006,
90.700.441]; Dutch Inter University Cardiology Institute Netherlands
(ICIN); Netherlands Heart Foundation [NHS2010B280]; Netherlands
Organization for Scientific Research [016.136.055]; Bristol-Myers
Squibb; Established Clinical Investigator of the Netherlands Heart
Foundation [2001 D 032]; European commission [223004]; Netherlands
Genomics Initiative (Netherlands Consortium for Healthy Aging)
[050-060-810]; Federal Ministry of Education and Research [01ZZ9603,
01ZZ0103, 01ZZ0403, 03IS2061A, 03ZIK012]; Ministry of Cultural Affairs;
Social Ministry of the Federal State of Mecklenburg-West Pomerania;
Siemens Healthcare, Erlangen, Germany; Federal State of Mecklenburg-West
Pomerania; Netherlands Organisation of Scientific Research NWO
Investments [175.010.2005.011, 911-03-012]; Research Institute for
Diseases in the Elderly [014-93-015]; Netherlands Genomics Initiative
(NGI)/Netherlands Organisation for Scientific Research (NWO)
[050-060-810]; Erasmus MC; Erasmus University Rotterdam; Netherlands
Organisation for Scientific Research (NWO); Development (ZonMw);
Research Institute for Diseases in the Elderly (RIDE) the Netherlands
Genomics Initiative (NGI); Ministry of Education, Culture and Science;
the Ministry of Health Welfare and Sport; European Commission (DG XII);
Municipality of Rotterdam; Fondation Leducq [14CVD01]; Doris Duke
Charitable Foundation Clinical Scientist Development Award [2014105];
[N01-HC-85239]; [N01-HC-85079]; [N01-HC-85080]; [N01-HC-85081];
[N01-HC-85082]; [N01-HC-85083]; [N01-HC-85084]; [N01-HC-85085];
[N01-HC-85086]; [N01-HC-35129]; [N01 HC-15103]; [N01 HC-55222];
[N01-HC-75150]; [N01-HC-45133]; [HHSN268200800007C];
[HHSN268201200036C]; [HL080295]; [HL087652]; [HL103612]; [HL105756];
[HL120393]
FX The study was supported by the German Federal Ministry of Education and
Research (BMBF) in the context of the German National Genome Research
Network (NGFN), the German National Competence network on atrial
fibrillation (AFNET), the Leducq Foundation (07-CVD 03), the D.W.
Reynolds Foundation Clinical Cardiovascular Research Center at Johns
Hopkins University, and the Bioinformatics for the Functional Analysis
of Mammalian Genomes program (BFAM) by grants to Stefan Kaab (01GS0499,
01GI0204, 01GS0838). The KORA study was initiated and financed by the
Helmholtz Zentrum Munchen - German Research Center for Environmental
Health, which is funded by the German Federal Ministry of Education and
Research (BMBF) and by the State of Bavaria. Furthermore, KORA research
was supported within the Munich Center of Health Sciences (MC-Health),
Ludwig-Maximilians-Universitat, as part of LMUinnovativ. Dr. Sinner is
supported by the German Heart Foundation. The Atherosclerosis Risk in
Communities Study is carried out as a collaborative study supported by
National Heart, Lung, and Blood Institute contracts (HHSN268201100005C,
HHSN268201100006C, HHSN268201100007C, HHSN268201100008C,
HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, and
HHSN268201100012C,), R01HL087641, R01HL59367, R01HL086694, and
R01HL111314; National Human Genome Research Institute contract
U01HG004402; and National Institutes of Health contract
HHSN268200625226C. Dr. Alonso is supported by grant 16EIA26410001 from
the American Heart Association. The authors thank the staff and
participants of the ARIC study for their important contributions.
Infrastructure was partly supported by Grant Number UL1RR025005, a
component of the National Institutes of Health and NIH Roadmap for
Medical Research. This CHS research was supported by NHLBI contracts
N01-HC-85239, N01-HC-85079, N01-HC-85080, N01-HC-85081, N01-HC-85082,
N01-HC-85083, N01-HC-85084, N01-HC-85085, N01-HC-85086; N01-HC-35129,
N01 HC-15103, N01 HC-55222, N01-HC-75150, N01-HC-45133,
HHSN268200800007C, HHSN268201200036C and NHLBI grants HL080295,
HL087652, HL103612, HL105756, HL120393 with additional contribution from
NINDS. Additional support was provided through AG-023629, AG-15928,
AG-20098, and AG-027058 from the NIA. See also
http://www.chs-nhlbi.org/pi.htm. The Cleveland Clinic AF study was
supported by NIH grants to Drs. Chung, Barnard, Smith, and Van Wagoner
(R01HL090620, R01HL111314), an NIH/NCRR CTSA grant (1UL-RR024989), Heart
and Vascular Institute Philanthropic grant, Department of Cardiovascular
Medicine, Cleveland Clinic (Chung), and a Leducq Fondation grant
07-CVD-03 (Van Wagoner). The Framingham Heart Study is conducted and
supported by the NHLBI in collaboration with Boston University (Contract
No. N01-HC-25195; HHSN268201500001I). This project also was supported by
NIH grants to Drs. Ellinor, Benjamin, and Lunetta (1RO1HL092577) and
Benjamin and Ellinor (1R01HL128914). LURIC was supported by the 7th
Framework Program (AtheroRemo, grant agreement number 201668 and
RiskyCAD, grant agreement number 305739) of the EU. The PREVEND study is
supported by the Dutch Kidney Foundation (grant E0.13), the National
Institutes of Health (grant 2R01LM010098), The Netherlands organization
for health research and development (NWO-Groot grant 175.010.2007.006,
ZonMw grant 90.700.441), and the Dutch Inter University Cardiology
Institute Netherlands (ICIN), and the Netherlands Heart Foundation
(grant NHS2010B280). Dr. M. Rienstra is supported by a grant from the
Netherlands Organization for Scientific Research (Veni grant 016.136.;
055). There are no relations with industry. The PROSPER study was
supported by an investigator initiated grant obtained from Bristol-Myers
Squibb. Prof. Dr. J. W. Jukema is an Established Clinical Investigator
of the Netherlands Heart Foundation (grant 2001 D 032). Support for
genotyping was provided by the seventh framework program of the European
commission (grant 223004) and by the Netherlands Genomics Initiative
(Netherlands Consortium for Healthy Aging grant 050-060-810). SHIP is
part of the Community Medicine Research net of the University of
Greifswald, Germany, which is funded by the Federal Ministry of
Education and Research (grants no. 01ZZ9603, 01ZZ0103, and 01ZZ0403),
the Ministry of Cultural Affairs as well as the Social Ministry of the
Federal State of Mecklenburg-West Pomerania, and the network 'Greifswald
Approach to Individualized Medicine (GANI_MED)' funded by the Federal
Ministry of Education and Research (grant 03IS2061A). Genome-wide data
have been supported by the Federal Ministry of Education and Research
(grant no. 03ZIK012) and a joint grant from Siemens Healthcare,
Erlangen, Germany and the Federal State of Mecklenburg-West Pomerania.
The University of Greifswald is a member of the 'Center of Knowledge
Interchange' program of the Siemens AG and the Cache Campus program of
the InterSystems GmbH. The generation and management of GWAS genotype
data for the Rotterdam Study is supported by the Netherlands
Organisation of Scientific Research NWO Investments (nr.
175.010.2005.011, 911-03-012). This study is funded by the Research
Institute for Diseases in the Elderly (014-93-015; RIDE2), the
Netherlands Genomics Initiative (NGI)/Netherlands Organisation for
Scientific Research (NWO) project nr. 050-060-810. The Rotterdam Study
is supported by the Erasmus MC and Erasmus University Rotterdam; the
Netherlands Organisation for Scientific Research (NWO); the Netherlands
Organisation for Health Research and Development (ZonMw); the Research
Institute for Diseases in the Elderly (RIDE) the Netherlands Genomics
Initiative (NGI); the Ministry of Education, Culture and Science; the
Ministry of Health Welfare and Sport; the European Commission (DG XII);
and the Municipality of Rotterdam. Dr. Ellinor is supported by grants
from the National Institutes of Health (HL104156, HL105780, HL065962).
Dr. Ellinor is also supported by an Established Investigator Award from
the American Heart Association (13EIA14220013) and by support from the
Fondation Leducq (14CVD01). Dr. Lubitz is supported by NIH grants
K23HL114724, and a Doris Duke Charitable Foundation Clinical Scientist
Development Award 2014105.
NR 32
TC 1
Z9 1
U1 2
U2 2
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2045-2322
J9 SCI REP-UK
JI Sci Rep
PD NOV 8
PY 2016
VL 6
AR 35371
DI 10.1038/srep35371
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EB3RL
UT WOS:000387283300001
PM 27824142
ER
PT J
AU Perner, J
Provaznik, J
Schrenkova, J
Urbanova, V
Ribeiro, JMC
Kopacek, P
AF Perner, Jan
Provaznik, Jan
Schrenkova, Jana
Urbanova, Veronika
Ribeiro, Jose M. C.
Kopacek, Petr
TI RNA-seq analyses of the midgut from blood- and serum-fed Ixodes ricinus
ticks
SO SCIENTIFIC REPORTS
LA English
DT Article
ID GLUTATHIONE-PEROXIDASE GENE; BOOPHILUS-MICROPLUS; SALIVARY-GLANDS;
CATTLE TICK; HAEMAPHYSALIS-LONGICORNIS; MOLECULAR-CLONING;
AEDES-AEGYPTI; LYME-DISEASE; HARD TICK; ORNITHODOROS-MOUBATA
AB Adult females of the genus Ixodes imbibe blood meals exceeding about 100 times their own weight within 7-9 days. During this period, ticks internalise components of host blood by endocytic digest cells that line the tick midgut epithelium. Using RNA-seq, we aimed to characterise the midgut transcriptome composition in adult Ixodes ricinus females during early and late phase of engorgement. To address specific adaptations to the haemoglobin-rich diet, we compared the midgut transcriptomes of genetically homogenous female siblings fed either bovine blood or haemoglobin-depleted serum. We noted that tick gut transcriptomes are subject to substantial temporal-dependent expression changes between day 3 and day 8 of feeding. In contrast, the number of transcripts significantly affected by the presence or absence of host red blood cells was low. Transcripts relevant to the processes associated with blood-meal digestion were analysed and involvement of selected encoded proteins in the tick midgut physiology discussed. A total of 7215 novel sequences from I. ricinus were deposited in public databases as an additional outcome of this study. Our results broaden the current knowledge of tick digestive system and may lead to the discovery of potential molecular targets for efficient tick control.
C1 [Perner, Jan; Schrenkova, Jana; Urbanova, Veronika; Kopacek, Petr] Acad Sci Czech Republic, Ctr Biol, Inst Parasitol, Branisovska 31, Ceske Budejovice 37005, Czech Republic.
[Provaznik, Jan] Acad Sci Czech Republic, Ctr Biol, Inst Entomol, Branisovska 31, Ceske Budejovice 37005, Czech Republic.
[Ribeiro, Jose M. C.] NIAID, Sect Vector Biol, Lab Malaria & Vector Res, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
RP Perner, J (reprint author), Acad Sci Czech Republic, Ctr Biol, Inst Parasitol, Branisovska 31, Ceske Budejovice 37005, Czech Republic.
EM perner@paru.cas.cz
OI Ribeiro, Jose/0000-0002-9107-0818
FU Czech Science Foundation [13-11043S, 15-12006Y]; Division of Intramural
Research, National Institute of Allergy and Infectious Diseases,
National Institutes of Health [ZIA AI000810-19]
FX This project was primarily supported by the Czech Science
Foundation-grant No. 13-11043S to P.K. V.U. was supported by the Czech
Science Foundation grant. No. 15-12006Y and J.M.R. by the Division of
Intramural Research, National Institute of Allergy and Infectious
Diseases, National Institutes of Health grant ZIA AI000810-19. The
authors gratefully acknowledge the assistance of Prof. Vladimir Benes
(Genomics Core Facility, EMBL Heidelberg) during the experimental
design.
NR 82
TC 0
Z9 0
U1 10
U2 10
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2045-2322
J9 SCI REP-UK
JI Sci Rep
PD NOV 8
PY 2016
VL 6
AR 36695
DI 10.1038/srep36695
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EB4FC
UT WOS:000387324300001
PM 27824139
ER
PT J
AU Kellman, P
Xue, H
Olivieri, LJ
Cross, RR
Grant, EK
Fontana, M
Ugander, M
Moon, JC
Hansen, MS
AF Kellman, Peter
Xue, Hui
Olivieri, Laura J.
Cross, Russell R.
Grant, Elena K.
Fontana, Marianna
Ugander, Martin
Moon, James C.
Hansen, Michael S.
TI Dark blood late enhancement imaging
SO JOURNAL OF CARDIOVASCULAR MAGNETIC RESONANCE
LA English
DT Article
DE Late enhancement; Gadolinium; Myocardial infarction; Dark blood;
Ablation; Scar; PSIR; MOCO; LGE
ID LATE-GADOLINIUM-ENHANCEMENT; MYOCARDIAL-INFARCTION; MAGNETIC-RESONANCE;
IRREVERSIBLE INJURY; CONTRAST; MRI; HEART; RECONSTRUCTION; DISTINCTION;
DISEASE
AB Background: Bright blood late gadolinium enhancement (LGE) imaging typically achieves excellent contrast between infarcted and normal myocardium. However, the contrast between the myocardial infarction (MI) and the blood pool is frequently suboptimal. A large fraction of infarctions caused by coronary artery disease are subendocardial and thus adjacent to the blood pool. It is not infrequent that sub-endocardial MIs are difficult to detect or clearly delineate.
Methods: In this present work, an inversion recovery (IR) T2 preparation was combined with single shot steady state free precession imaging and respiratory motion corrected averaging to achieve dark blood LGE images with good signal to noise ratio while maintaining the desired spatial and temporal resolution. In this manner, imaging was conducted free-breathing, which has benefits for image quality, patient comfort, and clinical workflow in both adults and children. Furthermore, by using a phase sensitive inversion recovery reconstruction the blood signal may be made darker than the myocardium (i.e., negative signal values) thereby providing contrast between the blood and both the MI and remote myocardium. In the proposed approach, a single T1-map scout was used to measure the myocardial and blood T1 using a MOdified Look-Locker Inversion recovery (MOLLI) protocol and all protocol parameters were automatically calculated from these values within the sequence thereby simplifying the user interface.
Results: The contrast to noise ratio (CNR) between MI and remote myocardium was measured in n = 30 subjects with subendocardial MI using both bright blood and dark blood protocols. The CNR for the dark blood protocol had a 13 % loss compared to the bright blood protocol. The CNR between the MI and blood pool was positive for all dark blood cases, and was negative in 63 % of the bright blood cases. The conspicuity of subendocardial fibrosis and MI was greatly improved by dark blood (DB) PSIR as well as the delineation of the subendocardial border.
Conclusions: Free-breathing, dark blood PSIR LGE imaging was demonstrated to improve the visualization of subendocardial MI and fibrosis in cases with low contrast with adjacent blood pool. The proposed method also improves visualization of thin walled fibrous structures such as atrial walls and valves, as well as papillary muscles.
C1 [Kellman, Peter; Xue, Hui; Hansen, Michael S.] NHLBI, NIH, DHHS, 10 Ctr Dr MSC 1061, Bethesda, MD 20892 USA.
[Olivieri, Laura J.; Cross, Russell R.; Grant, Elena K.] Childrens Natl Med Ctr, 111 Michigan Ave,NW, Washington, DC 20010 USA.
[Fontana, Marianna] UCL, Royal Free Hosp, Natl Amyloidosis Ctr, Sch Med, London, England.
[Ugander, Martin] Karolinska Inst, Dept Clin Physiol, Stockholm, Sweden.
[Ugander, Martin] Karolinska Univ Hosp, Stockholm, Sweden.
[Moon, James C.] St Bartholomews Hosp, Barts Heart Ctr, London, England.
RP Kellman, P (reprint author), NHLBI, NIH, DHHS, 10 Ctr Dr MSC 1061, Bethesda, MD 20892 USA.
EM kellman@nih.gov
FU National Heart, Lung and Blood Institute, National Institutes of Health
by the Division of Intramural Research
FX Supported by the National Heart, Lung and Blood Institute, National
Institutes of Health by the Division of Intramural Research.
NR 30
TC 0
Z9 0
U1 1
U2 1
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1097-6647
EI 1532-429X
J9 J CARDIOVASC MAGN R
JI J. Cardiov. Magn. Reson.
PD NOV 7
PY 2016
VL 18
AR 77
DI 10.1186/s12968-016-0297-3
PG 11
WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical
Imaging
SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine &
Medical Imaging
GA EC3RP
UT WOS:000388043600001
PM 27817748
ER
PT J
AU Murugesan, S
Hong, JS
Yi, J
Li, D
Beach, JR
Shao, L
Meinhardt, J
Madison, G
Wu, XF
Betzig, E
Hammer, JA
AF Murugesan, Sricharan
Hong, Jinsung
Yi, Jason
Li, Dong
Beach, Jordan R.
Shao, Lin
Meinhardt, John
Madison, Grey
Wu, Xufeng
Betzig, Eric
Hammer, John A.
TI Formin-generated actomyosin arcs propel T cell receptor microcluster
movement at the immune synapse
SO JOURNAL OF CELL BIOLOGY
LA English
DT Article
ID IMMUNOLOGICAL SYNAPSE; ACTIN CYTOSKELETON; F-ACTIN; SIGNAL-TRANSDUCTION;
RETROGRADE FLOW; MYOSIN IIA; ACTIVATION; ORGANIZATION; MOLECULES;
ADHESION
AB Actin assembly and inward flow in the plane of the immunological synapse (IS) drives the centralization of T cell receptor microclusters (TCR MCs) and the integrin leukocyte functional antigen 1 (LFA-1). Using structured-illumination microscopy (SIM), we show that actin arcs populating the medial, lamella-like region of the IS arise from linear actin filaments generated by one or more formins present at the IS distal edge. After traversing the outer, Arp2/3-generated, lamellipodia-like region of the IS, these linear filaments are organized by myosin II into antiparallel concentric arcs. Three-dimensional SIM shows that active LFA-1 often aligns with arcs, whereas TCR MCs commonly reside between arcs, and total internal reflection fluorescence SIM shows TCR MCs being swept inward by arcs. Consistently, disrupting actin arc formation via formin inhibition results in less centralized TCR MCs, missegregated integrin clusters, decreased T-B cell adhesion, and diminished TCR signaling. Together, our results define the origin, organization, and functional significance of a major actomyosin contractile structure at the IS that directly propels TCR MC transport.
C1 [Murugesan, Sricharan; Hong, Jinsung; Yi, Jason; Beach, Jordan R.; Meinhardt, John; Madison, Grey; Wu, Xufeng; Hammer, John A.] NHLBI, Cell Biol & Physiol Ctr, NIH, Bethesda, MD 20892 USA.
[Li, Dong; Shao, Lin; Betzig, Eric] Howard Hughes Med Inst, Janelia Res Campus, Ashburn, VA 20147 USA.
[Li, Dong] Chinese Acad Sci, Inst Biophys, Natl Lab Biomacromol, Beijing 100101, Peoples R China.
RP Hammer, JA (reprint author), NHLBI, Cell Biol & Physiol Ctr, NIH, Bethesda, MD 20892 USA.
EM hammerj@nhlbi.nih.gov
OI Murugesan, Sricharan/0000-0003-3045-3513
FU Intramural National Heart, Lung, and Blood Institute [1ZIAHL006121-04]
FX This work was supported by Intramural National Heart, Lung, and Blood
Institute grant 1ZIAHL006121-04 to J.A. Hammer.
NR 62
TC 2
Z9 2
U1 4
U2 4
PU ROCKEFELLER UNIV PRESS
PI NEW YORK
PA 950 THIRD AVE, 2ND FLR, NEW YORK, NY 10022 USA
SN 0021-9525
EI 1540-8140
J9 J CELL BIOL
JI J. Cell Biol.
PD NOV 7
PY 2016
VL 215
IS 3
BP 383
EP 399
DI 10.1083/jcb.201603080
PG 17
WC Cell Biology
SC Cell Biology
GA EB8JI
UT WOS:000387636900013
PM 27799367
ER
PT J
AU Gopinath, C
Law, WD
Rodreguez-Molina, JF
Prasad, AB
Song, LY
Crawford, GE
Mullikin, JC
Svaren, J
Antonellis, A
AF Gopinath, Chetna
Law, William D.
Rodriguez-Molina, Jose F.
Prasad, Arjun B.
Song, Lingyun
Crawford, Gregory E.
Mullikin, James C.
Svaren, John
Antonellis, Anthony
TI Stringent comparative sequence analysis reveals SOX10 as a putative
inhibitor of glial cell differentiation
SO BMC GENOMICS
LA English
DT Article
DE Comparative sequence analysis; Transcriptional regulation;
Ultra-conserved sequences; Myelination; Schwann cells; SOX10
ID TRANSCRIPTION FACTOR SOX10; MYELIN-ASSOCIATED GLYCOPROTEIN;
PERIPHERAL-NERVE MYELINATION; MARIE-TOOTH-DISEASE; SCHWANN-CELLS;
OLIGODENDROCYTE DIFFERENTIATION; PROTEIN; GENE; EXPRESSION;
IDENTIFICATION
AB Background: The transcription factor SOX10 is essential for all stages of Schwann cell development including myelination. SOX10 cooperates with other transcription factors to activate the expression of key myelin genes in Schwann cells and is therefore a context-dependent, pro-myelination transcription factor. As such, the identification of genes regulated by SOX10 will provide insight into Schwann cell biology and related diseases. While genome-wide studies have successfully revealed SOX10 target genes, these efforts mainly focused on myelinating stages of Schwann cell development. We propose that less-biased approaches will reveal novel functions of SOX10 outside of myelination.
Results: We developed a stringent, computational-based screen for genome-wide identification of SOX10 response elements. Experimental validation of a pilot set of predicted binding sites in multiple systems revealed that SOX10 directly regulates a previously unreported alternative promoter at SOX6, which encodes a transcription factor that inhibits glial cell differentiation. We further explored the utility of our computational approach by combining it with DNase-seq analysis in cultured Schwann cells and previously published SOX10 ChIP-seq data from rat sciatic nerve. Remarkably, this analysis enriched for genomic segments that map to loci involved in the negative regulation of gliogenesis including SOX5, SOX6, NOTCH1, HMGA2, HES1, MYCN, ID4, and ID2. Functional studies in Schwann cells revealed that: (1) all eight loci are expressed prior to myelination and down-regulated subsequent to myelination; (2) seven of the eight loci harbor validated SOX10 binding sites; and (3) seven of the eight loci are down-regulated upon repressing SOX10 function.
Conclusions: Our computational strategy revealed a putative novel function for SOX10 in Schwann cells, which suggests a model where SOX10 activates the expression of genes that inhibit myelination during non-myelinating stages of Schwann cell development. Importantly, the computational and functional datasets we present here will be valuable for the study of transcriptional regulation, SOX protein function, and glial cell biology.
C1 [Gopinath, Chetna; Antonellis, Anthony] Univ Michigan, Sch Med, Cellular & Mol Biol Program, Ann Arbor, MI 48109 USA.
[Law, William D.; Antonellis, Anthony] Univ Michigan, Sch Med, Dept Human Genet, Ann Arbor, MI 48109 USA.
[Rodriguez-Molina, Jose F.] Univ Wisconsin, Cellular & Mol Pathol Program, Madison, WI 53706 USA.
[Prasad, Arjun B.; Mullikin, James C.] NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA.
[Song, Lingyun; Crawford, Gregory E.] Duke Univ, Med Ctr, Ctr Genom & Computat Biol, Durham, NC 27708 USA.
[Crawford, Gregory E.] Duke Univ, Med Ctr, Dept Pediat, Durham, NC 27708 USA.
[Svaren, John] Univ Wisconsin, Waisman Ctr, Madison, WI 53706 USA.
[Svaren, John] Univ Wisconsin, Dept Comparat Biosci, Madison, WI 53706 USA.
[Antonellis, Anthony] Univ Michigan, Sch Med, Dept Neurol, Ann Arbor, MI 48109 USA.
RP Antonellis, A (reprint author), Univ Michigan, Sch Med, Cellular & Mol Biol Program, Ann Arbor, MI 48109 USA.; Antonellis, A (reprint author), Univ Michigan, Sch Med, Dept Human Genet, Ann Arbor, MI 48109 USA.; Antonellis, A (reprint author), Univ Michigan, Sch Med, Dept Neurol, Ann Arbor, MI 48109 USA.
EM antonell@umich.edu
OI Svaren, John/0000-0003-2963-7921
FU National Institute of Neurological Diseases and Stroke [NS073748,
NS083841]; Intramural Research Program of the National Human Genome
Research Institute; Cellular and Molecular Biology Program at the
University of Michigan; National Institutes of Health Genetics Training
Grant [GM007544]; EDGE Award from the Endowment for the Basic Sciences
at the University of Michigan; National Science Foundation
FX This project was funded by the National Institute of Neurological
Diseases and Stroke (NS073748 to A.A. and NS083841 to J.S.) and the
Intramural Research Program of the National Human Genome Research
Institute. C.G. was supported by funds from the Cellular and Molecular
Biology Program at the University of Michigan. W.D.L. was supported by
the National Institutes of Health Genetics Training Grant (GM007544) and
an EDGE Award from the Endowment for the Basic Sciences at the
University of Michigan. J.F.R-.M. was supported by a National Science
Foundation Pre-Doctoral Fellowship.
NR 60
TC 0
Z9 0
U1 1
U2 1
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2164
J9 BMC GENOMICS
JI BMC Genomics
PD NOV 7
PY 2016
VL 17
AR 887
DI 10.1186/s12864-016-3167-3
PG 16
WC Biotechnology & Applied Microbiology; Genetics & Heredity
SC Biotechnology & Applied Microbiology; Genetics & Heredity
GA EB2IO
UT WOS:000387183000008
PM 27821050
ER
PT J
AU Faison, SL
Schindler, CW
Goldberg, SR
Wang, JB
AF Faison, Shamia L.
Schindler, Charles W.
Goldberg, Steven R.
Wang, Jia Bei
TI l-tetrahydropalmatine reduces nicotine self-administration and
reinstatement in rats
SO BMC PHARMACOLOGY & TOXICOLOGY
LA English
DT Article
DE levo-Tetrahydropalmatine; Nicotine; Addiction
ID LEVO-TETRAHYDROPALMATINE; SMOKING-CESSATION; DOPAMINE RELEASE; PARTIAL
AGONIST; ADDICTION; COCAINE; DEPENDENCE; BRAIN; REINFORCEMENT;
VARENICLINE
AB Background: The negative consequences of nicotine use are well known and documented, however, abstaining from nicotine use and achieving abstinence poses a major challenge for the majority of nicotine users trying to quit. l-Tetrahydropalmatine (l-THP), a compound extracted from the Chinese herb Corydalis, displayed utility in the treatment of cocaine and heroin addiction via reduction of drug-intake and relapse. The present study examined the effects of l-THP on abuse-related effects of nicotine.
Methods: Self-administration and reinstatement testing was conducted. Rats trained to self-administer nicotine (0.03 mg/kg/injection) under a fixed-ratio 5 schedule (FR5) of reinforcement were pretreated with l-THP (3 or 5 mg/kg), varenicline (1 mg/kg), bupropion (40 mg/kg), or saline before daily 2-h sessions. Locomotor, food, and microdialysis assays were also conducted in separate rats.
Results: l-THP significantly reduced nicotine self-administration (SA). l-THP's effect was more pronounced than the effect of varenicline and similar to the effect of bupropion. In reinstatement testing, animals were pretreated with the same compounds, challenged with nicotine (0.3 mg/kg, s.c.), and reintroduced to pre-extinction conditions. l-THP blocked reinstatement of nicotine seeking more effectively than either varenicline or bupropion. Locomotor data revealed that therapeutic doses of l-THP had no inhibitory effects on ambulatory ability and that l-THP (3 and 5 mg/kg) significantly blocked nicotine induced hyperactivity when administered before nicotine. In in-vivo microdialysis experiments, l-THP, varenicline, and bupropion alone elevated extracellular dopamine (DA) levels in the nucleus accumbens shell (nAcb).
Conclusions: Since l-THP reduces nicotine taking and blocks relapse it could be a useful alternative to varenicline and bupropion as a treatment for nicotine addiction.
C1 [Faison, Shamia L.; Wang, Jia Bei] Univ Maryland, Sch Pharm, Dept Pharmaceut Sci, Baltimore, MD 21201 USA.
[Faison, Shamia L.; Schindler, Charles W.; Goldberg, Steven R.] NIDA, Preclin Pharmacol Sect, Behav Neurosci Res Branch, NIH,US Dept HHS, Baltimore, MD USA.
RP Wang, JB (reprint author), Univ Maryland, Sch Pharm, Dept Pharmaceut Sci, Baltimore, MD 21201 USA.
EM jwang@rx.umaryland.edu
FU National Institutes of Health National Institute on Drug Abuse
[DP1DA031401, 3DP1DA031401-02S1]; Intramural Research Program of NIDA,
NIH, DHHS
FX This work was supported by the National Institutes of Health National
Institute on Drug Abuse [Avant-Garde Award DP1DA031401] to J.B.W. with
diversity supplemental grant to S.L.F (3DP1DA031401-02S1). This research
was also supported in part by the Intramural Research Program of NIDA,
NIH, DHHS.
NR 34
TC 0
Z9 0
U1 3
U2 3
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 2050-6511
J9 BMC PHARMACOL TOXICO
JI BMC Pharmacol. Toxicol.
PD NOV 7
PY 2016
VL 17
AR 49
DI 10.1186/s40360-016-0093-6
PG 12
WC Pharmacology & Pharmacy; Toxicology
SC Pharmacology & Pharmacy; Toxicology
GA EB3RH
UT WOS:000387282900001
PM 27817750
ER
PT J
AU Yi, J
Manna, A
Barr, VA
Hong, J
Neuman, KC
Samelson, LE
AF Yi, Jason
Manna, Asit
Barr, Valarie A.
Hong, Jennifer
Neuman, Keir C.
Samelson, Lawrence E.
TI madSTORM: a superresolution technique for large-scale multiplexing at
single-molecule accuracy
SO MOLECULAR BIOLOGY OF THE CELL
LA English
DT Article
ID T-CELL-RECEPTOR; OPTICAL RECONSTRUCTION MICROSCOPY; PAIR
CORRELATION-ANALYSIS; FLUORESCENT-PROBES; LOCALIZATION MICROSCOPY;
IMMUNOLOGICAL SYNAPSE; ACTIN; ORGANIZATION; STORM; PALM
AB Investigation of heterogeneous cellular structures using single-molecule localization microscopy has been limited by poorly defined localization accuracy and inadequate multiplexing capacity. Using fluorescent nanodiamonds as fiducial markers, we define and achieve localization precision required for single-molecule accuracy in dSTORM images. Coupled with this advance, our new multiplexing strategy, madSTORM, allows accurate targeting of multiple molecules using sequential binding and elution of fluorescent antibodies. madSTORM is used on an activated T-cell to localize 25 epitopes, 14 of which are on components of the same multimolecular T-cell receptor complex. We obtain an average localization precision of 2.6 nm, alignment error of 2.0 nm, and < 0.01% cross-talk. Combining these technical advances affords the ability to move beyond obtaining superresolved structures to defining spatial relationships among constituent molecules within structures. Probing the molecular topology of complex signaling cascades and other heterogeneous networks is feasible with madSTORM.
C1 [Yi, Jason; Manna, Asit; Barr, Valarie A.; Samelson, Lawrence E.] NHLBI, Lab Cellular & Mol Biol, NCI, NIH, Bethesda, MD 20892 USA.
[Hong, Jennifer; Neuman, Keir C.] NHLBI, Lab Single Mol Biophys, NIH, Bethesda, MD 20892 USA.
RP Samelson, LE (reprint author), NHLBI, Lab Cellular & Mol Biol, NCI, NIH, Bethesda, MD 20892 USA.
EM samelsonl@mail.nih.gov
RI Neuman, Keir/F-7400-2011
OI Neuman, Keir/0000-0002-0863-5671
FU Intramural Research Program of the National Cancer Institute Center for
Cancer Research
FX We thank Connie Sommers for providing CD4+ mouse T-cells,
Sunmee Huh for help with illustration, Xufeng Wu for access to the Nikon
N-STORM microscope, and Hari Shroff for comments on the manuscript. This
research was supported by the Intramural Research Program of the
National Cancer Institute Center for Cancer Research.
NR 44
TC 1
Z9 1
U1 8
U2 8
PU AMER SOC CELL BIOLOGY
PI BETHESDA
PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA
SN 1059-1524
EI 1939-4586
J9 MOL BIOL CELL
JI Mol. Biol. Cell
PD NOV 7
PY 2016
VL 27
IS 22
BP 3591
EP 3600
DI 10.1091/mbc.E16-05-0330
PG 10
WC Cell Biology
SC Cell Biology
GA EB5CR
UT WOS:000387391400020
PM 27708141
ER
PT J
AU Zhou, ZJ
Hu, R
Wang, LR
Sun, CJ
Fu, G
Gao, JH
AF Zhou, Zijian
Hu, Rong
Wang, Lirong
Sun, Chengjie
Fu, Gang
Gao, Jinhao
TI Water bridge coordination on the metal-rich facets of Gd2O3 nanoplates
confers high T-1 relaxivity
SO NANOSCALE
LA English
DT Article
ID MRI CONTRAST AGENTS; GADOLINIUM-BASED CONTRAST; IRON-OXIDE
NANOPARTICLES; EXPOSED 001 FACETS; SELECTIVE HYDROGENATION; RELAXATION;
NANOSHEETS; NANOCRYSTALS; THERAPY; DESIGN
AB The realization of the nature of water coordination on the solid surfaces may provoke an essential understanding of T-1 relaxation enhancement, especially in nanoparticulate systems. We report herein that the T-1 relaxivity of Gd2O3 nanoplates is highly dependent on water coordinating behaviors on different surfaces. Gd2O3 nanoplates with metal-rich {100} facets showed an approximately 4-fold higher r(1) value compared to that with oxygen-terminated {111} facets. Density functional theory (DFT) calculations show that the enhanced T-1 relaxivity of Gd2O3 {100} nanoplates may be ascribed to the high density of accessible Gd3+, fast exchange of water, and more importantly, multicenter (one-to-two) coordination for water molecules with magnetic centers on the metal-rich surface.
C1 [Zhou, Zijian; Hu, Rong; Wang, Lirong; Sun, Chengjie; Fu, Gang; Gao, Jinhao] Xiamen Univ, State Key Lab Phys Chem Solid Surfaces, MOE Key Lab Spectrochem Anal & Instrumentat, Xiamen 361005, Peoples R China.
[Zhou, Zijian; Hu, Rong; Wang, Lirong; Sun, Chengjie; Fu, Gang; Gao, Jinhao] Xiamen Univ, Key Lab Chem Biol Fujian Prov, Coll Chem & Chem Engn, Xiamen 361005, Peoples R China.
[Zhou, Zijian] Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD 20892 USA.
RP Gao, JH (reprint author), Xiamen Univ, State Key Lab Phys Chem Solid Surfaces, MOE Key Lab Spectrochem Anal & Instrumentat, Xiamen 361005, Peoples R China.; Gao, JH (reprint author), Xiamen Univ, Key Lab Chem Biol Fujian Prov, Coll Chem & Chem Engn, Xiamen 361005, Peoples R China.
EM jhgao@xmu.edu.cn
FU National Key Basic Research Program of China [2013CB933901,
2014CB744502, 2014CB932004]; National Natural Science Foundation of
China [21222106, 21521004, 81370042, 81430041]; Fok Ying Tung Education
Foundation [142012]; Intramural Research Program, National Institute of
Biomedical Imaging and Bioengineering, National Institutes of Health
FX This work was supported by the National Key Basic Research Program of
China (2013CB933901, 2014CB744502, and 2014CB932004), the National
Natural Science Foundation of China (21222106, 21521004, 81370042, and
81430041), Fok Ying Tung Education Foundation (142012), and the
Intramural Research Program, National Institute of Biomedical Imaging
and Bioengineering, National Institutes of Health.
NR 48
TC 0
Z9 0
U1 27
U2 27
PU ROYAL SOC CHEMISTRY
PI CAMBRIDGE
PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS,
ENGLAND
SN 2040-3364
EI 2040-3372
J9 NANOSCALE
JI Nanoscale
PD NOV 7
PY 2016
VL 8
IS 41
BP 17887
EP 17894
DI 10.1039/c6nr06444b
PG 8
WC Chemistry, Multidisciplinary; Nanoscience & Nanotechnology; Materials
Science, Multidisciplinary; Physics, Applied
SC Chemistry; Science & Technology - Other Topics; Materials Science;
Physics
GA EB4HI
UT WOS:000387331100021
PM 27722744
ER
PT J
AU Kim, SH
Vlijm, R
van der Torre, J
Dalal, Y
Dekker, C
AF Kim, Sung Hyun
Vlijm, Rifka
van der Torre, Jaco
Dalal, Yamini
Dekker, Cees
TI CENP-A and H3 Nucleosomes Display a Similar Stability to Force-Mediated
Disassembly
SO PLOS ONE
LA English
DT Article
ID HISTONE CHAPERONE NAP1; CENTROMERIC NUCLEOSOME; SINGLE-MOLECULE;
MAGNETIC TWEEZERS; CRYSTAL-STRUCTURE; CHROMATIN FIBERS; KINETOCHORE;
DNA; DYNAMICS; CORE
AB Centromere-specific nucleosomes are a central feature of the kinetochore complex during mitosis, in which microtubules exert pulling and pushing forces upon the centromere. CENP-A nucleosomes have been assumed to be structurally unique, thereby providing resilience under tension relative to their H3 canonical counterparts. Here, we directly test this hypothesis by subjecting CENP-A and H3 octameric nucleosomes, assembled on random or on centromeric DNA sequences, to varying amounts of applied force by using single-molecule magnetic tweezers. We monitor individual disassembly events of CENP-A and H3 nucleosomes. Regardless of the DNA sequence, the force-mediated disassembly experiments for CENP-A and H3 nucleosomes demonstrate similar rupture forces, life time residency and disassembly steps. From these experiments, we conclude that CENP-A does not, by itself, contribute unique structural features to the nucleosome that lead to a significant resistance against force-mediated disruption. The data present insights into the mechanistic basis for how CENP-A nucleosomes might contribute to the structural foundation of the centromere in vivo.
C1 [Kim, Sung Hyun; Vlijm, Rifka; van der Torre, Jaco; Dekker, Cees] Delft Univ Technol, Kavli Inst Nanosci Delft, Dept Bionanosci, Delft, Netherlands.
[Dalal, Yamini] NCI, Chromatin Struct & Epigenet Mech Unit, Lab Receptor Biol & Gene Express, Ctr Canc Res,NHI, Bethesda, MD 20892 USA.
[Vlijm, Rifka] German Canc Res Ctr, Div Opt Nanoscopy, Heidelberg, Germany.
RP Dekker, C (reprint author), Delft Univ Technol, Kavli Inst Nanosci Delft, Dept Bionanosci, Delft, Netherlands.; Dalal, Y (reprint author), NCI, Chromatin Struct & Epigenet Mech Unit, Lab Receptor Biol & Gene Express, Ctr Canc Res,NHI, Bethesda, MD 20892 USA.
EM dalaly@mail.nih.gov; C.Dekker@tudelft.nl
FU ERC Advanced Grant SynDiv [669598]; Netherlands Organization for
Scientific Research (NWO/OCW) [as part of the Frontiers of Nanoscience
program]; intramural research program of the Center for Cancer Research
under the auspices of the National Cancer Institute at the NIH
FX This work was supported by the ERC Advanced Grant SynDiv [grant number
669598 to C.D.]; the Netherlands Organization for Scientific Research
(NWO/OCW) [as part of the Frontiers of Nanoscience program]. YD is
funded by the intramural research program of the Center for Cancer
Research under the auspices of the National Cancer Institute at the NIH.
NR 71
TC 1
Z9 1
U1 6
U2 6
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD NOV 7
PY 2016
VL 11
IS 11
AR e0165078
DI 10.1371/journal.pone.0165078
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EB8BB
UT WOS:000387614800006
PM 27820823
ER
PT J
AU Weth-Malsch, D
Langeslag, M
Beroukas, D
Zangrandi, L
Kastenberger, I
Quarta, S
Malsch, P
Kalpachidou, T
Schwarzer, C
Proia, RL
Haberberger, RV
Kress, M
AF Weth-Malsch, Daniela
Langeslag, Michiel
Beroukas, Dimitra
Zangrandi, Luca
Kastenberger, Iris
Quarta, Serena
Malsch, Philipp
Kalpachidou, Theodora
Schwarzer, Christoph
Proia, Richard L.
Haberberger, Rainer V.
Kress, Michaela
TI Ablation of Sphingosine 1-Phosphate Receptor Subtype 3 Impairs
Hippocampal Neuron Excitability In vitro and Spatial Working Memory In
vivo
SO FRONTIERS IN CELLULAR NEUROSCIENCE
LA English
DT Article
DE sphingosine 1-phosphate; S1P receptor 3; hippocampus; working memory;
neuron excitability
ID PROTEIN-COUPLED RECEPTOR; MOUSE VENTRICULAR FIBROBLASTS;
CENTRAL-NERVOUS-SYSTEM; MOSSY FIBER TERMINALS; SENSORY NEURONS; MICE
LACKING; SPHINGOSINE-1-PHOSPHATE; BRAIN; ALTERNATION; LESIONS
AB Understanding the role of the bioactive lipid mediator sphingosine 1-phosphate (S1P) within the central nervous system has recently gained more and more attention, as it has been connected to major diseases such as multiple sclerosis and Alzheimer's disease. Even though much data about the functions of the five S1P receptors has been collected for other organ systems, we still lack a complete understanding for their specific roles, in particular within the brain. Therefore, it was the aim of this study to further elucidate the role of S1P receptor subtype 3 (S1P(3)) in vivo and in vitro with a special focus on the hippocampus. Using an S1P(3) knock-out mouse model we applied a range of behavioral tests, performed expression studies, and whole cell patch clamp recordings in acute hippocampal slices. We were able to show that S1P(3) deficient mice display a significant spatial working memory deficit within the T-maze test, but not in anxiety related tests. Furthermore, S1p3 mRNA was expressed throughout the hippocampal formation. Principal neurons in area CA3 lacking S1P(3) showed significantly increased interspike intervals and a significantly decreased input resistance. Upon stimulation with S1P CA3 principal neurons from both wildtype and S1P(3)(-/-) mice displayed significantly increased evoked EPSC amplitudes and decay times, whereas rise times remained unchanged. These results suggest a specific involvement of S1P(3) for the establishment of spatial working memory and neuronal excitability within the hippocampus.
C1 [Weth-Malsch, Daniela; Langeslag, Michiel; Quarta, Serena; Malsch, Philipp; Kalpachidou, Theodora; Kress, Michaela] Med Univ Innsbruck, Div Physiol, Dept Physiol & Med Phys, Innsbruck, Austria.
[Beroukas, Dimitra; Haberberger, Rainer V.] Flinders Univ S Australia, Anat & Histol, Adelaide, SA, Australia.
[Beroukas, Dimitra; Haberberger, Rainer V.] Flinders Univ S Australia, Ctr Neurosci, Adelaide, SA, Australia.
[Zangrandi, Luca; Kastenberger, Iris; Schwarzer, Christoph] Med Univ Innsbruck, Dept Pharmacol, Innsbruck, Austria.
[Proia, Richard L.] NIDDK, Genet Dev & Dis Branch, Bethesda, MD 20892 USA.
RP Kress, M (reprint author), Med Univ Innsbruck, Div Physiol, Dept Physiol & Med Phys, Innsbruck, Austria.
EM Michaela.Kress@i-med.ac.at
OI Haberberger, Rainer Viktor/0000-0001-8043-3786
FU Intramural Research Programs of the National Instituts of Health;
National Institute of Diabetes and Digestive and Kidney Diseases;
Austrian Research Funding Agency FWF [P20562, P25345, SPIN-01206-B6];
European FP7 programme (ncRNAPain) [GA 602133]
FX This work was supported by the Intramural Research Programs of the
National Instituts of Health, National Institute of Diabetes and
Digestive and Kidney Diseases to RP, the Austrian Research Funding
Agency FWF (project grants P20562, P25345, and SPIN-01206-B6) and the
European FP7 programme (ncRNAPain - GA 602133) to MK. The authors thank
Markus Doblander for expert technical assistance.
NR 48
TC 0
Z9 0
U1 5
U2 5
PU FRONTIERS MEDIA SA
PI LAUSANNE
PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015,
SWITZERLAND
SN 1662-5102
J9 FRONT CELL NEUROSCI
JI Front. Cell. Neurosci.
PD NOV 7
PY 2016
VL 10
AR 258
DI 10.3389/fncel.2016.00258
PG 12
WC Neurosciences
SC Neurosciences & Neurology
GA EA9QA
UT WOS:000386977700001
PM 27872583
ER
PT J
AU Chin, PY
Dorian, CL
Hutchinson, MR
Olson, DM
Rice, KC
Moldenhauer, LM
Robertson, SA
AF Chin, Peck Yin
Dorian, Camilla L.
Hutchinson, Mark R.
Olson, David M.
Rice, Kenner C.
Moldenhauer, Lachlan M.
Robertson, Sarah A.
TI Novel Toll-like receptor-4 antagonist (+)-naloxone protects mice from
inflammation-induced preterm birth
SO SCIENTIFIC REPORTS
LA English
DT Article
ID FETAL-GROWTH RESTRICTION; FUSOBACTERIUM-NUCLEATUM; BLOOD MONOCYTES;
LABOR; EXPRESSION; NALOXONE; PARTURITION; MEMBRANES; LIPOPOLYSACCHARIDE;
RESPONSES
AB Toll-like receptor 4 (TLR4) activation by bacterial infection, or by sterile inflammatory insult is a primary trigger of spontaneous preterm birth. Here we utilize mouse models to investigate the efficacy of a novel small molecule TLR4 antagonist, (+)-naloxone, the non-opioid isomer of the opioid receptor antagonist (-)-naloxone, in infection-associated preterm birth. Treatment with (+)-naloxone prevented preterm delivery and alleviated fetal demise in utero elicited by i.p. LPS administration in late gestation. A similar effect with protection from preterm birth and perinatal death, and partial correction of reduced birth weight and postnatal mortality, was conferred by (+)-naloxone administration after intrauterine administration of heat-killed E. coli. Local induction by E. coli of inflammatory cytokine genes Il1b, Il6, Tnf and Il10 in fetal membranes was suppressed by (+)-naloxone, and cytokine expression in the placenta, and uterine myometrium and decidua, was also attenuated. These data demonstrate that inhibition of TLR4 signaling with the novel TLR4 antagonist (+)-naloxone can suppress the inflammatory cascade of preterm parturition, to prevent preterm birth and perinatal death. Further studies are warranted to investigate the utility of small molecule inhibition of TLR-driven inflammation as a component of strategies for fetal protection and delaying preterm birth in the clinical setting.
C1 [Chin, Peck Yin; Dorian, Camilla L.; Moldenhauer, Lachlan M.; Robertson, Sarah A.] Univ Adelaide, Robinson Res Inst, Adelaide, SA 5005, Australia.
[Chin, Peck Yin; Dorian, Camilla L.; Hutchinson, Mark R.; Moldenhauer, Lachlan M.; Robertson, Sarah A.] Univ Adelaide, Adelaide Med Sch, Adelaide, SA 5005, Australia.
[Hutchinson, Mark R.] Australian Res Council, Ctr Excellence Nanoscale BioPhoton, Adelaide, SA 5005, Australia.
[Olson, David M.] Univ Alberta, Dept Obstet & Gynecol, Edmonton, AB T6G 2S2, Canada.
[Olson, David M.] Univ Alberta, Dept Pediat, Edmonton, AB T6G 2S2, Canada.
[Olson, David M.] Univ Alberta, Dept Physiol, Edmonton, AB T6G 2S2, Canada.
[Rice, Kenner C.] NIDA, Chem Biol Res Branch, Bethesda, MD 20892 USA.
[Rice, Kenner C.] NIAAA, NIH, Bethesda, MD 20892 USA.
RP Robertson, SA (reprint author), Univ Adelaide, Robinson Res Inst, Adelaide, SA 5005, Australia.; Robertson, SA (reprint author), Univ Adelaide, Adelaide Med Sch, Adelaide, SA 5005, Australia.
EM sarah.robertson@adelaide.edu.au
OI Hutchinson, Mark/0000-0003-2154-5950
FU National Health and Medical Research Council of Australia [APP1026178,
APP465423]; Canadian Institutes of Health Research [2011-09-15];
Australian Research Council [DP110100297]; NIH Intramural Research
Programs of the National Institute on Drug Abuse (NIDA); National
Institute of Alcohol Abuse and Alcoholism (NIAAA)
FX This work was supported by project and fellowship grants from the
National Health and Medical Research Council of Australia (APP1026178
and APP465423), the Canadian Institutes of Health Research (2011-09-15)
and the Australian Research Council (DP110100297). A portion of this
work was supported by the NIH Intramural Research Programs of the
National Institute on Drug Abuse (NIDA) and the National Institute of
Alcohol Abuse and Alcoholism (NIAAA).
NR 65
TC 0
Z9 0
U1 8
U2 8
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2045-2322
J9 SCI REP-UK
JI Sci Rep
PD NOV 7
PY 2016
VL 6
AR 36112
DI 10.1038/srep36112
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EA9ZD
UT WOS:000387002300001
PM 27819333
ER
PT J
AU Xu, XQ
Zhang, B
Yang, SL
An, S
Ribeiro, JMC
Andersen, JF
AF Xu, Xueqing
Zhang, Bei
Yang, Shilong
An, Su
Ribeiro, Jose M. C.
Andersen, John F.
TI Structure and Function of FS50, a salivary protein from the flea
Xenopsylla cheopis that blocks the sodium channel Na(V)1.5
SO SCIENTIFIC REPORTS
LA English
DT Article
ID BETA-SCORPION TOXIN; ACTIVATION; INHIBITOR; BINDING; INSECT; PEPTIDE;
GLANDS; TOOLS; SITE
AB Naturally occurring toxins have been invaluable tools for the study of structural and functional relationships of voltage-gated sodium channels (VGSC). Few studies have been made of potential channel-modulating substances from blood-feeding arthropods. He we describe the characterization FS50, a salivary protein from the flea, Xenopsylla cheopis, that exhibits an inhibitory activity against the Na(V)1.5 channel with an IC50 of 1.58 mu M. The pore-blocking mechanism of this toxin is evident from the kinetics of activation and inactivation suggesting that FS50 does not interfere with the voltage sensor of Na(V)1.5. FS50 exhibits high specificity for Na(V)1.5, since 10 mu M FS50 had no discernable effect on voltage-gated Na+, K+ and Ca2+ channels in rat dorsal root ganglia or VGSC forms individually expressed in HEK 293T cells. Furthermore, intravenous injection of FS50 into rats and monkeys elicited recovery from arrhythmia induced by BaCl2, as would be expected from a blockade of Na(V)1.5. The crystal structure of FS50 revealed a beta alpha beta beta domain similar to that of scorpion beta toxin and a small N-terminal beta alpha beta domain. Site-directed mutagenesis experiments have implicated a basic surface including the side chains of Arg 6, His 11 and Lys 32 as potentially important in the FS50 Na(V)1.5 interaction.
C1 [Xu, Xueqing; Zhang, Bei] Southern Med Univ, Sch Pharmaceut Sci, Guangdong Prov Key Lab New Drug Screening, Guangzhou 510515, Guangdong, Peoples R China.
[Xu, Xueqing; Ribeiro, Jose M. C.; Andersen, John F.] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA.
[Yang, Shilong; An, Su] Chinese Acad Sci, Kunming Inst Zool, Lab Anim Models & Human Dis Mech, Kunming 650223, Yunnan, Peoples R China.
RP Xu, XQ (reprint author), Southern Med Univ, Sch Pharmaceut Sci, Guangdong Prov Key Lab New Drug Screening, Guangzhou 510515, Guangdong, Peoples R China.; Xu, XQ; Andersen, JF (reprint author), NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA.
EM xu2003@smu.edu.cn; jandersen@niaid.nih.gov
FU Chinese National Natural Science Foundation [3137078]; Chinese Ministry
of Science and Technology [2010CB529800]; National Institutes of Health
intramural research program of NIAID
FX The authors thank the staff of the Southeast Regional Collaborative
Access Team, Advanced Photon Source, Argonne National Laboratory for
assistance with X-ray data collection. This work was supported in part
by the Chinese National Natural Science Foundation (3137078), the
Chinese Ministry of Science and Technology (2010CB529800) and the
National Institutes of Health intramural research program of NIAID.
NR 30
TC 0
Z9 0
U1 4
U2 4
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2045-2322
J9 SCI REP-UK
JI Sci Rep
PD NOV 7
PY 2016
VL 6
AR 36574
DI 10.1038/srep36574
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EB0VJ
UT WOS:000387064000001
PM 27819327
ER
PT J
AU Lee, J
Chowell, G
Jung, E
AF Lee, Jonggul
Chowell, Gerardo
Jung, Eunok
TI A dynamic compartmental model for the Middle East respiratory syndrome
outbreak in the Republic of Korea: A retrospective analysis on control
interventions and superspreading events
SO JOURNAL OF THEORETICAL BIOLOGY
LA English
DT Article
DE MERS; Superspreader; Nosocomial infections; Mathematical modeling;
Republic of Korea; Infectious diseases
ID HEALTH-CARE FACILITIES; MERS-COV; INFECTIOUS-DISEASES; CORONAVIRUS;
TRANSMISSION; SARS; EPIDEMIOLOGY
AB The 2015 Middle East respiratory syndrome (MERS) outbreak in the Republic of Korea has provided an opportunity to improve our understanding of the spread of MERS linked to healthcare settings. Here we designed a dynamic transmission model to analyze the MERS outbreak in the Republic of Korea based on confirmed cases reported during the period May 20 July 4, 2015. Our model explicitly incorporates superspreading events and time-dependent transmission and isolation rates. Our model was able to provide a good fit to the trajectory of the outbreak and was useful to analyze the role of hypothetical control scenarios. Specifically, we assessed the impact of the timing of control measures, especially associated with a reduction of the transmission rate and diagnostic delays on outbreak size and duration. Early interventions within 1 week after the epidemic onset, for instance, including the initial government announcement to the public about the list of hospitals exposed to MERS coronavirus (MERS-CoV), show a promising means to reduce the size (>71%) and duration (>35%) of the MERS epidemic. Finally, we also present results of an uncertainty analysis focused on the role of superspreading events. (C) 2016 The Authors. Published by Elsevier Ltd.
C1 [Lee, Jonggul; Jung, Eunok] Konkuk Univ, Dept Math, Seoul 05029, South Korea.
[Chowell, Gerardo] Georgia State Univ, Sch Publ Hlth, Atlanta, GA 30303 USA.
[Chowell, Gerardo] NIH, Div Int Epidemiol & Populat Studies, Fogarty Int Ctr, Bldg 10, Bethesda, MD 20892 USA.
RP Jung, E (reprint author), Konkuk Univ, Dept Math, Seoul 05029, South Korea.
EM jack9872@konkuk.ac.kr; gchowell@gsu.edu; junge@konkuk.ac.kr
FU Korea National Research Foundation (NRF) - Korea government (MEST)
[NRF-2015R1A2A1A15054463]; Konkuk University
FX The research work of Jung was supported by the Korea National Research
Foundation (NRF) grant funded by the Korea government (MEST)
(NRF-2015R1A2A1A15054463). Jung's work is also resulted from the Konkuk
University research support program.
NR 32
TC 0
Z9 0
U1 8
U2 8
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0022-5193
EI 1095-8541
J9 J THEOR BIOL
JI J. Theor. Biol.
PD NOV 7
PY 2016
VL 408
BP 118
EP 126
DI 10.1016/j.jtbi.2016.08.009
PG 9
WC Biology; Mathematical & Computational Biology
SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational
Biology
GA DX8IG
UT WOS:000384630700012
PM 27521523
ER
PT J
AU Lewis, DEA
Gussin, GN
Adhya, S
AF Lewis, Dale E. A.
Gussin, Gary N.
Adhya, Sankar
TI New Insights into the Phage Genetic Switch: Effects of Bacteriophage
Lambda Operator Mutations on DNA Looping and Regulation of P-R, P-L, and
P-RM
SO JOURNAL OF MOLECULAR BIOLOGY
LA English
DT Article
DE prophage lambdagenetic switch; DNA looping; CI repressor; transcription
ID OPEN COMPLEX-FORMATION; RNA-POLYMERASE; TRANSCRIPTION INITIATION; PRM
PROMOTER; REPRESSOR SYNTHESIS; NEGATIVE CONTROL; PAIR DELETION; CI
REPRESSOR; IN-VITRO; ACTIVATION
AB One of the best understood systems in genetic regulatory biology is the so-called "genetic switch" that determines the choice the phage-encoded CI repressor binds cooperatively to tripartite operators, O-L and O-R, in a defined pattern, thus blocking the transcription at two lytic promoters, P-L and P-R, and auto-regulating the promoter, P-RM, which directs CI synthesis by the prophage. Fine-tuning of the maintenance of lysogeny is facilitated by interactions between CI dimers bound to O-R and O-L through the formation of a loop by the intervening DNA segment. By using a purified in vitro transcription system, we have genetically dissected the roles of individual operator sites in the formation of the DNA loop and thus have gained several new and unexpected insights into the system. First, although both O-R and O-L are tripartite, the presence of only a single active CI binding site in one of the two operators is sufficient for DNA loop formation. Second, in PL, unlike in P-R, the promoter distal operator site, O(L)3, is sufficient to directly repress PL. Third, DNA looping mediated by the formation of CI octamers arising through the interaction of pairs of dimers bound to adjacent operator sites in OR and OL does not require OR and OL to be aligned "in register", that is, CI bound to "out-of-register" sub-operators, for example, O(L)1 similar to O(1)2 and O(R)2 similar to O(R)3, can also mediate loop formation. Finally, based on an examination of the mechanism of activation of PRM when only O(R)1 or O(R)2 are wild type, we hypothesize that RNA polymerase bound at P-R interferes with DNA loop formation. Thus, the formation of DNA loops involves potential interactions between proteins bound at numerous cis-acting sites, which therefore very subtly contribute to the regulation of the "switch". (C) 2016 Published by Elsevier Ltd.
C1 [Lewis, Dale E. A.; Adhya, Sankar] NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Gussin, Gary N.] Univ Iowa, Dept Biol, Iowa City, IA 52242 USA.
RP Adhya, S (reprint author), NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM sadhya@helix.nih.gov
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, Center for
Cancer Research. We thank our colleagues in the laboratory for helpful
discussions.
NR 49
TC 0
Z9 0
U1 3
U2 3
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0022-2836
EI 1089-8638
J9 J MOL BIOL
JI J. Mol. Biol.
PD NOV 6
PY 2016
VL 428
IS 22
BP 4438
EP 4456
DI 10.1016/j.jmb.2016.08.027
PG 19
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA EC1AG
UT WOS:000387835300003
PM 27670714
ER
PT J
AU Oronsky, B
Caroen, S
Zeman, K
Quinn, M
Brzezniak, C
Scicinski, J
Cabrales, P
Reid, TR
Trepel, JB
Abrouk, ND
Larson, C
Oronsky, A
Lybeck, HE
Day, RM
Carter, CA
AF Oronsky, Bryan
Caroen, Scott
Zeman, Karen
Quinn, Mary
Brzezniak, Christina
Scicinski, Jan
Cabrales, Pedro
Reid, Tony R.
Trepel, Jane B.
Abrouk, Nacer D.
Larson, Christopher
Oronsky, Arnold
Lybeck, Harry E.
Day, Regina M.
Carter, Corey A.
TI A Partial Response to Reintroduced Chemotherapy in a Resistant Small
Cell Lung Cancer Patient After Priming with RRx-001
SO CLINICAL MEDICINE INSIGHTS-ONCOLOGY
LA English
DT Article
DE resistant SCLC; RRx-001; resistance reversal; resensitization; platinum
doublets; epigenetic
ID MELANOMA BRAIN METASTASES; DRUG-RESISTANCE; TOPOTECAN; THERAPY;
RADIOTHERAPY; MECHANISMS; UPDATE; TRIALS
AB As an exceedingly recalcitrant and highly aggressive tumor type without Food and Drug Administration-approved treatment or a known cure, the prognosis of recurrent extensive stage platinum-resistant/refractory small cell lung cancer (SCLC) is worse than other types of lung cancer, and many other tumor types, given a response rate of less than 10% and an overall survival of less than six months. It was broadly classified into three groups based on the initial response to cisplatin/etoposide therapy, platinum-refractory, platinum-resistant, and platinum-sensitive, extensive stage SCLC inevitably relapses, at which point the only standard options are to rechallenge with the first-line chemotherapeutic regimen in the case of sensitive disease or to start the topoisomerase I inhibitor, topotecan. Sensitive disease is defined by a response to the first-line therapy and a treatment-free interval of at least 90 days, while the definitions of refractory and resistant disease, respectively, are nonresponse to the first-line treatment or relapse within 90 days. As an important predictor of response to the second-line treatment, the clinical cutoff of three months (or two months in some cases) for resistant and sensitive disease, which along with performance status prognostically separates patients into high-and low-risk categories, dictates subsequent management. This case report presents a resistant SCLC patient enrolled on a Phase II clinical trial called QUADRUPLE THREAT (formerly TRIPLE THREAT; NCT02489903) who responded to reintroduced platinum doublets after sequential priming with the resistance-reversing epi-immunotherapeutic agent, RRx-001. In the QUADRUPLE THREAT clinical trial, both during priming with RRx-001 and during sequential treatment with platinum doublets, the patient maintained a good quality of life and performance status.
C1 [Oronsky, Bryan; Caroen, Scott; Scicinski, Jan] EpicentRx, Mountain View, CA 94040 USA.
[Zeman, Karen; Quinn, Mary; Brzezniak, Christina; Carter, Corey A.] Walter Reed Mil Med Ctr, Bethesda, MD USA.
[Cabrales, Pedro] UCSD, Dept Bioengn, La Jolla, CA USA.
[Reid, Tony R.; Larson, Christopher] UCSD, Moores Canc Ctr, La Jolla, CA USA.
[Trepel, Jane B.] NCI, Ctr Canc Res, Bethesda, MD 20892 USA.
[Abrouk, Nacer D.] Innovexe, Palo Alto, CA USA.
[Oronsky, Arnold] InterWest Partners, Menlo Pk, CA USA.
[Lybeck, Harry E.] Univ Helsinki, Helsinki, Finland.
[Day, Regina M.] Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA.
RP Caroen, S (reprint author), EpicentRx, Mountain View, CA 94040 USA.
EM scaroen@epicentrx.com
NR 26
TC 0
Z9 0
U1 4
U2 4
PU LIBERTAS ACAD
PI AUCKLAND
PA PO BOX 300-874, ALBANY 0752, AUCKLAND, 00000, NEW ZEALAND
SN 1179-5549
J9 CLIN MED INSIGHTS-ON
JI Clin. Med. Insights-Oncol.
PD NOV 6
PY 2016
VL 10
BP 105
EP 108
DI 10.4137/CMO.S40429
PG 4
WC Oncology
SC Oncology
GA EA9CL
UT WOS:000386938600001
PM 27840583
ER
PT J
AU Blanquart, F
Grabowski, MK
Herbeck, J
Nalugoda, F
Serwadda, D
Eller, MA
Robb, ML
Gray, R
Kigozi, G
Laeyendecker, O
Lythgoe, KA
Nakigozi, G
Quinn, TC
Reynolds, SJ
Wawer, MJ
Fraser, C
AF Blanquart, Francois
Grabowski, Mary Kate
Herbeck, Joshua
Nalugoda, Fred
Serwadda, David
Eller, Michael A.
Robb, Merlin L.
Gray, Ronald
Kigozi, Godfrey
Laeyendecker, Oliver
Lythgoe, Katrina A.
Nakigozi, Gertrude
Quinn, Thomas C.
Reynolds, Steven J.
Wawer, Maria J.
Fraser, Christophe
TI A transmission-virulence evolutionary trade-off explains attenuation of
HIV-1 in Uganda
SO ELIFE
LA English
DT Article
ID GENITAL ULCER DISEASE; SIMPLEX-VIRUS TYPE-2; VIRAL LOAD; PROGNOSTIC
MARKERS; PROSPECTIVE COHORT; SET-POINT; PROGRESSION; POPULATION;
INFECTION; RAKAI
AB Evolutionary theory hypothesizes that intermediate virulence maximizes pathogen fitness as a result of a trade-off between virulence and transmission, but empirical evidence remains scarce. We bridge this gap using data from a large and long-standing HIV-1 prospective cohort, in Uganda. We use an epidemiological-evolutionary model parameterised with this data to derive evolutionary predictions based on analysis and detailed individual-based simulations. We robustly predict stabilising selection towards a low level of virulence, and rapid attenuation of the virus. Accordingly, set-point viral load, the most common measure of virulence, has declined in the last 20 years. Our model also predicts that subtype A is slowly outcompeting subtype D, with both subtypes becoming less virulent, as observed in the data. Reduction of set-point viral loads should have resulted in a 20% reduction in incidence, and a three years extension of untreated asymptomatic infection, increasing opportunities for timely treatment of infected individuals.
C1 [Blanquart, Francois; Lythgoe, Katrina A.; Fraser, Christophe] Imperial Coll London, MRC Ctr Outbreak Anal & Modelling, London, England.
[Blanquart, Francois; Lythgoe, Katrina A.; Fraser, Christophe] Imperial Coll London, Dept Infect Dis Epidemiol, London, England.
[Blanquart, Francois; Lythgoe, Katrina A.; Fraser, Christophe] Imperial Coll London, Sch Publ Hlth, London, England.
[Grabowski, Mary Kate; Gray, Ronald; Wawer, Maria J.] Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD USA.
[Grabowski, Mary Kate; Gray, Ronald; Wawer, Maria J.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD USA.
[Herbeck, Joshua] Univ Washington, Int Clin Res Ctr, Seattle, WA 98195 USA.
[Herbeck, Joshua] Univ Washington, Dept Global Hlth, Seattle, WA 98195 USA.
[Nalugoda, Fred; Serwadda, David; Gray, Ronald; Kigozi, Godfrey; Nakigozi, Gertrude] Rakai Hlth Sci Program, Entebbe, Uganda.
[Serwadda, David] Makerere Univ, Sch Publ Hlth, Kampala, Uganda.
[Eller, Michael A.; Robb, Merlin L.] Walter Reed Army Inst Res, US Mil HIV Res Program, Silver Spring, MD USA.
[Eller, Michael A.; Robb, Merlin L.] Henry M Jackson Fdn Adv Mil Med, Bethesda, MD USA.
[Laeyendecker, Oliver; Quinn, Thomas C.; Reynolds, Steven J.] NIAID, Immunoregulat Lab, NIH, Bldg 10, Bethesda, MD 20892 USA.
[Laeyendecker, Oliver; Quinn, Thomas C.; Reynolds, Steven J.] NIAID, Div Intramural Res, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Lythgoe, Katrina A.] Univ Oxford, Dept Zool, Oxford, England.
[Fraser, Christophe] Univ Oxford, Big Data Inst, Nuffield Dept Med, Li Ka Shing Ctr Hlth Informat & Discovery, Oxford, England.
RP Blanquart, F (reprint author), Imperial Coll London, MRC Ctr Outbreak Anal & Modelling, London, England.; Blanquart, F (reprint author), Imperial Coll London, Dept Infect Dis Epidemiol, London, England.; Blanquart, F (reprint author), Imperial Coll London, Sch Publ Hlth, London, England.
EM f.blanguart@imperial.ac.uk
OI Fraser, Christophe/0000-0003-2399-9657
FU European Commission [657768]; National Institute of Allergy and
Infectious Diseases [R01 AI29314, R01 A134826, U01 AI11171-01-02];
National Institute of Child Health and Development [5P30 HD 06268]; John
E. Fogarty Foundation for Persons with Intellectual and Developmental
Disabilities [5D43TW00010]; John Snow Inc. [5024-30]; Pfizer [5024-30];
Rockefeller Foundation; World Bank Group; National Institutes of Health
[P30AI027757, R01AI108490]; U.S. Department of Defense
[W81XWH-07-2-0067]; Henry M. Jackson Foundation [W81XWH-07-2-0067];
European Research Council [PBDR-339251]
FX European Commission Intra European Fellowship 657768 Francois Blanquart;
National Institute of Allergy and Infectious Diseases R01 AI29314 Mary
Kate Grabowski Fred Nalugoda David Serwadda Michael A Eller Merlin L
Robb Ronald Gray Godfrey Kigozi Oliver Laeyendecker Gertrude Nakigozi
Thomas C Quinn Steven J Reynolds Maria J Wawer; National Institute of
Child Health and Development 5P30 HD 06268 Mary Kate Grabowski Fred
Nalugoda David Serwadda Michael A Eller Merlin L Robb Ronald Gray
Godfrey Kigozi Oliver Laeyendecker Gertrude Nakigozi Thomas C Quinn
Steven J Reynolds Maria J Wawer; John E. Fogarty Foundation for Persons
with Intellectual and Developmental Disabilities 5D43TW00010 Mary Kate
Grabowski Fred Nalugoda David Serwadda Michael A Eller Merlin L Robb
Ronald Gray Godfrey Kigozi Oliver Laeyendecker Gertrude Nakigozi Thomas
C Quinn Steven J Reynolds Maria J Wawer; John Snow Inc. 5024-30 Mary
Kate Grabowski Fred Nalugoda David Serwadda Michael A Eller Merlin L
Robb Ronald Gray Godfrey Kigozi Oliver Laeyendecker Gertrude Nakigozi
Thomas C Quinn Steven J Reynolds Maria J Wawer; Pfizer 5024-30 Mary Kate
Grabowski Fred Nalugoda David Serwadda Michael A Eller Merlin L Robb
Ronald Gray Godfrey Kigozi Oliver Laeyendecker Gertrude Nakigozi Thomas
C Quinn Steven J Reynolds Maria J Wawer; Rockefeller Foundation Mary
Kate Grabowski Fred Nalugoda David Serwadda Michael A Eller Merlin L
Robb Ronald Gray Godfrey Kigozi Oliver Laeyendecker Gertrude Nakigozi
Thomas C Quinn Steven J Reynolds Maria J Wawer; World Bank Group Mary
Kate Grabowski Fred Nalugoda David Serwadda Michael A Eller Merlin L
Robb Ronald Gray Godfrey Kigozi Oliver Laeyendecker Gertrude Nakigozi
Thomas C Quinn Steven J Reynolds Maria J Wawer; National Institute of
Allergy and Infectious Diseases R01 A134826 Mary Kate Grabowski Fred
Nalugoda David Serwadda Michael A Eller Merlin L Robb Ronald Gray
Godfrey Kigozi Oliver Laeyendecker Gertrude Nakigozi Thomas C Quinn
Steven J Reynolds Maria J Wawer; National Institute of Allergy and
Infectious Diseases U01 AI11171-01-02 Mary Kate Grabowski Fred Nalugoda
David Serwadda Michael A Eller Merlin L Robb Ronald Gray Godfrey Kigozi
Oliver Laeyendecker Gertrude Nakigozi Thomas C Quinn Steven J Reynolds
Maria J Wawer; National Institutes of Health P30AI027757 Joshua Herbeck;
National Institutes of Health R01AI108490 Joshua Herbeck; U.S.
Department of Defense W81XWH-07-2-0067 Michael A Eller Merlin L Robb;
Henry M. Jackson Foundation W81XWH-07-2-0067 Michael A Eller Merlin L
Robb; European Research Council PBDR-339251 Christophe Fraser
NR 67
TC 3
Z9 3
U1 3
U2 3
PU ELIFE SCIENCES PUBLICATIONS LTD
PI CAMBRIDGE
PA SHERATON HOUSE, CASTLE PARK, CAMBRIDGE, CB3 0AX, ENGLAND
SN 2050-084X
J9 ELIFE
JI eLife
PD NOV 5
PY 2016
VL 5
AR e20492
DI 10.7554/eLife.20492
PG 31
WC Biology
SC Life Sciences & Biomedicine - Other Topics
GA ED2NJ
UT WOS:000388683400001
ER
PT J
AU Ratha, BN
Ghosh, A
Brender, JR
Gayen, N
Ilyas, H
Neeraja, C
Das, KP
Mandal, AK
Bhunia, A
AF Ratha, Bhisma N.
Ghosh, Anirban
Brender, Jeffrey R.
Gayen, Nilanjan
Ilyas, Humaira
Neeraja, Chilukoti
Das, Kali P.
Mandal, Atin K.
Bhunia, Anirban
TI Inhibition of Insulin Amyloid Fibrillation by a Novel Amphipathic
Heptapeptide: MECHANISTIC DETAILS STUDIED BY SPECTROSCOPY IN COMBINATION
WITH MICROSCOPY
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
DE amyloid; atomic force microscopy (AFM); fluorescence anisotropy;
inhibitor; insulin
ID TRANSFER DIFFERENCE NMR; AGGREGATION PATHWAYS; ALZHEIMERS-DISEASE; BETA
FIBRILS; PROTEINS; KINETICS; HEXAMER; BINDING; LIGAND; HELIX
AB The aggregation of insulin into amyloid fibers has been a limiting factor in the development of fast acting insulin analogues, creating a demand for excipients that limit aggregation. Despite the potential demand, inhibitors specifically targeting insulin have been few in number. Here we report a non-toxic and serum stable-designed heptapeptide, KR7 (KPWWPRR-NH2), that differs significantly from the primarily hydrophobic sequences that have been previously used to interfere with insulin amyloid fibrillation. Thioflavin T fluorescence assays, circular dichroism spectroscopy, and one-dimensional proton NMR experiments suggest KR7 primarily targets the fiber elongation step with little effect on the early oligomerization steps in the lag time period. From confocal fluorescence and atomic force microscopy experiments, the net result appears to be the arrest of aggregation in an early, non-fibrillar aggregation stage. This mechanism is noticeably different from previous peptide-based inhibitors, which have primarily shifted the lag time with little effect on later stages of aggregation. As insulin is an important model system for understanding protein aggregation, the new peptide may be an important tool for understanding peptide-based inhibition of amyloid formation.
C1 [Ratha, Bhisma N.; Ghosh, Anirban; Ilyas, Humaira; Bhunia, Anirban] Bose Inst, Dept Biophys, P 1-12 CIT Scheme 7 M, Kolkata 700054, India.
[Gayen, Nilanjan; Mandal, Atin K.] Bose Inst, Dept Mol Med, P 1-12 CIT Scheme 7 M, Kolkata 700054, India.
[Brender, Jeffrey R.] NIH, Radiat Biol Branch, Bethesda, MD 20814 USA.
[Neeraja, Chilukoti] TIFR Ctr Interdisciplinary Sci TCIS, Hyderabad 500075, Andhra Pradesh, India.
[Das, Kali P.] Bose Inst, Dept Chem, 93-1 APC Rd, Kolkata 700009, India.
RP Bhunia, A (reprint author), Bose Inst, Dept Biophys, P 1-12 CIT Scheme 7 M, Kolkata 700054, India.
EM anirbanbhunia@gmail.com
FU DBT, Government of India [BT/PR3106/INF/22/138/2011]
FX A. B. acknowledges DBT, Government of India, for infrastructure
development Fund BT/PR3106/INF/22/138/2011 to the Bose Institute for
procuring a 700-MHz NMR spectrometer with cryoprobe. Central Instrument
Facility (CIF) of Bose Institute is greatly acknowledged.
NR 66
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U1 15
U2 15
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
EI 1083-351X
J9 J BIOL CHEM
JI J. Biol. Chem.
PD NOV 4
PY 2016
VL 291
IS 45
BP 23545
EP 23556
DI 10.1074/jbc.M116.742460
PG 12
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA EC1RH
UT WOS:000387884400016
PM 27679488
ER
PT J
AU Dougherty, EJ
Elinoff, JM
Ferreyra, GA
Hou, A
Cai, RM
Sun, JF
Blaine, KP
Wang, SB
Danner, RL
AF Dougherty, Edward J.
Elinoff, Jason M.
Ferreyra, Gabriela A.
Hou, Angela
Cai, Rongman
Sun, Junfeng
Blaine, Kevin P.
Wang, Shuibang
Danner, Robert L.
TI Mineralocorticoid Receptor (MR) trans-Activation of Inflammatory AP-1
Signaling: DEPENDENCE ON DNA SEQUENCE, MR CONFORMATION, AND AP-1 FAMILY
MEMBER EXPRESSION
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
DE AP1 transcription factor (AP-1); glucocorticoid receptor; inflammation;
mineralocorticoid receptor; NF-B transcription factor; nuclear receptor;
trans-repression
ID NF-KAPPA-B; COMPOSITE RESPONSE ELEMENT; STEROID-HORMONE RECEPTORS;
PROSTATE CARCINOMA-CELLS; GLUCOCORTICOID-RECEPTOR; ACTIVATOR PROTEIN-1;
VASCULAR INFLAMMATION; MYOCARDIAL-INFARCTION; NEGATIVE REGULATION;
HEART-FAILURE
AB Glucocorticoids are commonly used to treat inflammatory disorders. The glucocorticoid receptor (GR) can tether to inflammatory transcription factor complexes, such as NFB and AP-1, and trans-repress the transcription of cytokines, chemokines, and adhesion molecules. In contrast, aldosterone and the mineralocorticoid receptor (MR) primarily promote cardiovascular inflammation by incompletely understood mechanisms. Although MR has been shown to weakly repress NFB, its role in modulating AP-1 has not been established. Here, the effects of GR and MR on NFB and AP-1 signaling were directly compared using a variety of ligands, two different AP-1 consensus sequences, GR and MR DNA-binding domain mutants, and siRNA knockdown or overexpression of core AP-1 family members. Both GR and MR repressed an NFB reporter without influencing p65 or p50 binding to DNA. Likewise, neither GR nor MR affected AP-1 binding, but repression or activation of AP-1 reporters occurred in a ligand-, AP-1 consensus sequence-, and AP-1 family member-specific manner. Notably, aldosterone interactions with both GR and MR demonstrated a potential to activate AP-1. DNA-binding domain mutations that eliminated the ability of GR and MR to cis-activate a hormone response element-driven reporter variably affected the strength and polarity of these responses. Importantly, MR modulation of NFB and AP-1 signaling was consistent with a trans-mechanism, and AP-1 effects were confirmed for specific gene targets in primary human cells. Steroid nuclear receptor trans-effects on inflammatory signaling are context-dependent and influenced by nuclear receptor conformation, DNA sequence, and the expression of heterologous binding partners. Aldosterone activation of AP-1 may contribute to its proinflammatory effects in the vasculature.
C1 [Dougherty, Edward J.; Elinoff, Jason M.; Ferreyra, Gabriela A.; Hou, Angela; Cai, Rongman; Sun, Junfeng; Blaine, Kevin P.; Wang, Shuibang; Danner, Robert L.] NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA.
[Hou, Angela] NYU, Langone Med Ctr, 550 1st Ave, New York, NY 10016 USA.
RP Dougherty, EJ; Danner, RL (reprint author), NIH, Dept Crit Care Med, 10 Ctr Dr,Rm 2C145, Bethesda, MD 20892 USA.
EM doughertye@cc.nih.gov; rdanner@nih.gov
FU National Institutes of Health intramural funds
FX This work was supported by National Institutes of Health intramural
funds. The authors declare that they have no conflicts of interest with
the contents of this article. The content is solely the responsibility
of the authors and does not necessarily represent the official views of
the National Institutes of Health.
NR 76
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U1 1
U2 1
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
EI 1083-351X
J9 J BIOL CHEM
JI J. Biol. Chem.
PD NOV 4
PY 2016
VL 291
IS 45
BP 23628
EP 23644
DI 10.1074/jbc.M116.732248
PG 17
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA EC1RH
UT WOS:000387884400023
PM 27650495
ER
PT J
AU Ritter, DI
Roychowdhury, S
Roy, A
Rao, S
Landrum, MJ
Sonkin, D
Shekar, M
Davis, CF
Hart, RK
Micheel, C
Weaver, M
Van Allen, EM
Parsons, DW
McLeod, HL
Watson, MS
Plon, SE
Kulkarni, S
Madhavan, S
AF Ritter, Deborah I.
Roychowdhury, Sameek
Roy, Angshumoy
Rao, Shruti
Landrum, Melissa J.
Sonkin, Dmitriy
Shekar, Mamatha
Davis, Caleb F.
Hart, Reece K.
Micheel, Christine
Weaver, Meredith
Van Allen, Eliezer M.
Parsons, Donald W.
McLeod, Howard L.
Watson, Michael S.
Plon, Sharon E.
Kulkarni, Shashikant
Madhavan, Subha
CA ClinGen Somatic Canc Working Grp
TI Somatic cancer variant curation and harmonization through consensus
minimum variant level data
SO GENOME MEDICINE
LA English
DT Article
DE Cancer genomics; Somatic variant interpretation; Data standard; Somatic
variant curation
ID MICROARRAY EXPERIMENT MIAME; DECISION-SUPPORT; MEDICINE; GENOME;
INFORMATION; PLATFORM; CHALLENGES; STANDARDS; ONCOLOGY; TUMOR
AB Background: To truly achieve personalized medicine in oncology, it is critical to catalog and curate cancer sequence variants for their clinical relevance. The Somatic Working Group (WG) of the Clinical Genome Resource (ClinGen), in cooperation with ClinVar and multiple cancer variant curation stakeholders, has developed a consensus set of minimal variant level data (MVLD). MVLD is a framework of standardized data elements to curate cancer variants for clinical utility. With implementation of MVLD standards, and in a working partnership with ClinVar, we aim to streamline the somatic variant curation efforts in the community and reduce redundancy and time burden for the interpretation of cancer variants in clinical practice.
Methods: We developed MVLD through a consensus approach by i) reviewing clinical actionability interpretations from institutions participating in the WG, ii) conducting extensive literature search of clinical somatic interpretation schemas, and iii) survey of cancer variant web portals. A forthcoming guideline on cancer variant interpretation, from the Association of Molecular Pathology (AMP), can be incorporated into MVLD.
Results: Along with harmonizing standardized terminology for allele interpretive and descriptive fields that are collected by many databases, the MVLD includes unique fields for cancer variants such as Biomarker Class, Therapeutic Context and Effect. In addition, MVLD includes recommendations for controlled semantics and ontologies. The Somatic WG is collaborating with ClinVar to evaluate MVLD use for somatic variant submissions. ClinVar is an open and centralized repository where sequencing laboratories can report summary-level variant data with clinical significance, and ClinVar accepts cancer variant data.
Conclusions: We expect the use of the MVLD to streamline clinical interpretation of cancer variants, enhance interoperability among multiple redundant curation efforts, and increase submission of somatic variants to ClinVar, all of which will enhance translation to clinical oncology practice.
C1 [Ritter, Deborah I.; Roy, Angshumoy; Parsons, Donald W.; Plon, Sharon E.; Kulkarni, Shashikant] Baylor Coll Med, Houston, TX 77030 USA.
[Ritter, Deborah I.; Roy, Angshumoy; Parsons, Donald W.; Plon, Sharon E.; Kulkarni, Shashikant] Texas Childrens Hosp, Houston, TX 77030 USA.
[Roychowdhury, Sameek] Ohio State Univ, Columbus, OH 43210 USA.
[Rao, Shruti; Madhavan, Subha] Georgetown Univ, Med Ctr, Innovat Ctr Biomed Informat, Washington, DC 20007 USA.
[Rao, Shruti; Madhavan, Subha] Georgetown Univ, Med Ctr, Lombardi Comprehens Canc Ctr, Washington, DC 20007 USA.
[Landrum, Melissa J.] Natl Ctr Biotechnol Informat, Bethesda, MD USA.
[Sonkin, Dmitriy] NCI, Rockville, MD USA.
[Shekar, Mamatha] Illumina, San Diego, CA USA.
[Davis, Caleb F.] MolecularMatch, Houston, TX USA.
[Hart, Reece K.] Invitae, San Francisco, CA USA.
[Micheel, Christine] Vanderbilt Univ, Sch Med, Nashville, TN 37212 USA.
[Weaver, Meredith] Amer Coll Med Genet & Genom, Bethesda, MD USA.
[Van Allen, Eliezer M.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[McLeod, Howard L.] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA.
RP Madhavan, S (reprint author), Georgetown Univ, Med Ctr, Innovat Ctr Biomed Informat, Washington, DC 20007 USA.; Madhavan, S (reprint author), Georgetown Univ, Med Ctr, Lombardi Comprehens Canc Ctr, Washington, DC 20007 USA.
EM sm696@georgetown.edu
OI Micheel, Christine/0000-0002-7744-9039; Hart, Reece/0000-0003-3463-0775
FU National Human Genome Research Institute; Eunice Kennedy Shriver
National Institute of Child Health and Human Development; National
Cancer Institute [U41 HG006834, U01 HG007436, U01 HG007437,
HHSN261200800001E]; Intramural Research Program of the NIH, National
Library of Medicine; NHGRI, BD2K Program [01HG008390]; NHGRI/NCI
[1U01HG006485]; [U01HG006492]; [K08CA188615]
FX ClinGen is funded by the National Human Genome Research Institute, with
additional funding from the Eunice Kennedy Shriver National Institute of
Child Health and Human Development and the National Cancer Institute
(U41 HG006834, U01 HG007436, U01 HG007437, HHSN261200800001E). ClinVar
is supported by the Intramural Research Program of the NIH, National
Library of Medicine. Additional funding: 01HG008390 (NHGRI, BD2K
Program) to SM; U01HG006492 and K08CA188615 to EMV. The
BASIC3 study is a Clinical Sequencing Exploratory Research
(CSER) program project supported by NHGRI/NCI 1U01HG006485 to AR, SEP,
and DWP.
NR 33
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U1 0
U2 0
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 NOV 4
PY 2016
VL 8
AR 117
DI 10.1186/s13073-016-0367-z
PG 9
WC Genetics & Heredity
SC Genetics & Heredity
GA EB8DS
UT WOS:000387621800001
PM 27814769
ER
PT J
AU Feunang, YD
Eisner, R
Knox, C
Chepelev, L
Hastings, J
Owen, G
Fahy, E
Steinbeck, C
Subramanian, S
Bolton, E
Greiner, R
Wishart, DS
AF Feunang, Yannick Djoumbou
Eisner, Roman
Knox, Craig
Chepelev, Leonid
Hastings, Janna
Owen, Gareth
Fahy, Eoin
Steinbeck, Christoph
Subramanian, Shankar
Bolton, Evan
Greiner, Russell
Wishart, David S.
TI ClassyFire: automated chemical classification with a comprehensive,
computable taxonomy
SO JOURNAL OF CHEMINFORMATICS
LA English
DT Article
DE Structure-based classification; Ontology; Taxonomy; Text-based search;
Inference; Annotation; Database; Data integration
ID METABOLOME DATABASE; SMALL MOLECULES; ONTOLOGY; DESIGN; CHEMISTRY; GENE;
TOOL
AB Background: Scientists have long been driven by the desire to describe, organize, classify, and compare objects using taxonomies and/or ontologies. In contrast to biology, geology, and many other scientific disciplines, the world of chemistry still lacks a standardized chemical ontology or taxonomy. Several attempts at chemical classification have been made; but they have mostly been limited to either manual, or semi-automated proof-of-principle applications. This is regrettable as comprehensive chemical classification and description tools could not only improve our understanding of chemistry but also improve the linkage between chemistry and many other fields. For instance, the chemical classification of a compound could help predict its metabolic fate in humans, its druggability or potential hazards associated with it, among others. However, the sheer number (tens of millions of compounds) and complexity of chemical structures is such that any manual classification effort would prove to be near impossible.
Results: We have developed a comprehensive, flexible, and computable, purely structure-based chemical taxonomy (ChemOnt), along with a computer program (ClassyFire) that uses only chemical structures and structural features to automatically assign all known chemical compounds to a taxonomy consisting of >4800 different categories. This new chemical taxonomy consists of up to 11 different levels (Kingdom, SuperClass, Class, SubClass, etc.) with each of the categories defined by unambiguous, computable structural rules. Furthermore each category is named using a consensus-based nomenclature and described (in English) based on the characteristic common structural properties of the compounds it contains. The ClassyFire webserver is freely accessible at http://classyfire.wishartlab.com/. Moreover, a Ruby API version is available at https://bitbucket.org/wishartlab/classyfire_api, which provides programmatic access to the ClassyFire server and database. ClassyFire has been used to annotate over 77 million compounds and has already been integrated into other software packages to automatically generate textual descriptions for, and/or infer biological properties of over 100,000 compounds. Additional examples and applications are provided in this paper.
Conclusion: ClassyFire, in combination with ChemOnt (ClassyFire's comprehensive chemical taxonomy), now allows chemists and cheminformaticians to perform large-scale, rapid and automated chemical classification. Moreover, a freely accessible API allows easy access to more than 77 million "ClassyFire" classified compounds. The results can be used to help annotate well studied, as well as lesser-known compounds. In addition, these chemical classifications can be used as input for data integration, and many other cheminformatics-related tasks.
C1 [Feunang, Yannick Djoumbou; Wishart, David S.] Univ Alberta, Dept Biol Sci, Edmonton, AB T6G 2E8, Canada.
[Eisner, Roman] Jobber Field Serv Software, 10520 Jasper Ave, Edmonton, AB T5J 1Z7, Canada.
[Knox, Craig; Greiner, Russell; Wishart, David S.] Univ Alberta, Dept Comp Sci, Edmonton, AB T6G 2E8, Canada.
[Wishart, David S.] Natl Inst Nanotechnol NINT, Natl Res Council, Edmonton, AB T6G 2M9, Canada.
[Chepelev, Leonid] Univ Ottawa, Ottawa Hosp, Dept Med Imaging, Civ Campus,1053 Carling Ave, Ottawa, ON K1Y 4E9, Canada.
[Hastings, Janna; Owen, Gareth; Steinbeck, Christoph] European Bioinformat Inst EMBL EBI, European Mol Biol Lab, Wellcome Trust Genome Campus, Cambridge, England.
[Fahy, Eoin; Subramanian, Shankar] Univ Calif La Jolla, Dept Bioengn, San Diego, CA 92093 USA.
[Bolton, Evan] Natl Lib Med, Dept Hlth & Human Serv, Natl Ctr Biotechnol Informat, NIH, 8600 Rockville Pike, Bethesda, MD 20894 USA.
[Greiner, Russell] Univ Alberta, Alberta Innovates Ctr Machine Learning AICML, Dept Comp Sci, 2-21 Athabasca Hall, Edmonton, AB T6G 2E8, Canada.
[Wishart, David S.] Univ Alberta, Metabol Innovat Ctr, Edmonton, AB T6G 2E9, Canada.
RP Wishart, DS (reprint author), Univ Alberta, Dept Biol Sci, Edmonton, AB T6G 2E8, Canada.; Wishart, DS (reprint author), Univ Alberta, Dept Comp Sci, Edmonton, AB T6G 2E8, Canada.; Wishart, DS (reprint author), Natl Inst Nanotechnol NINT, Natl Res Council, Edmonton, AB T6G 2M9, Canada.; Wishart, DS (reprint author), Univ Alberta, Metabol Innovat Ctr, Edmonton, AB T6G 2E9, Canada.
EM david.wishart@ualberta.ca
OI Steinbeck, Christoph/0000-0001-6966-0814
FU Genome Canada; Genome Alberta; Canadian Institutes of Health Research;
Alberta Innovates; National Research Council; National Institute of
Nanotechnology
FX Funding for this research has been provided by Genome Canada, Genome
Alberta, The Canadian Institutes of Health Research, Alberta Innovates,
The National Research Council and The National Institute of
Nanotechnology. The funders had no role in study design, data
collection. Data analysis, decision to publish, or preparation of the
manuscript.
NR 46
TC 0
Z9 0
U1 6
U2 6
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1758-2946
J9 J CHEMINFORMATICS
JI J. Cheminformatics
PD NOV 4
PY 2016
VL 8
AR 61
DI 10.1186/s13321-016-0174-y
PG 20
WC Chemistry, Multidisciplinary; Computer Science, Information Systems;
Computer Science, Interdisciplinary Applications
SC Chemistry; Computer Science
GA EB1DJ
UT WOS:000387086800001
ER
PT J
AU Kim, S
Bolton, EE
Bryant, SH
AF Kim, Sunghwan
Bolton, Evan E.
Bryant, Stephen H.
TI Similar compounds versus similar conformers: complementarity between
PubChem 2-D and 3-D neighboring sets
SO JOURNAL OF CHEMINFORMATICS
LA English
DT Article
DE PubChem; PubChem3D; Molecular similarity; Neighboring; Neighbor
Preference Index (NPI)
ID MOLECULAR DESCRIPTOR SPACE; GAUSSIAN DESCRIPTION; SHAPE; 2D;
COEFFICIENTS; INFORMATION; DIVERSITY; RESOURCE; DATABASE
AB Background: PubChem is a public repository for biological activities of small molecules. For the efficient use of its vast amount of chemical information, PubChem performs 2-dimensional (2-D) and 3-dimensional (3-D) neighborings, which precompute "neighbor" relationships between molecules in the PubChem Compound database, using the PubChem subgraph fingerprints-based 2-D similarity and the Gaussian-shape overlay-based 3-D similarity, respectively. These neighborings allow PubChem to provide the user with immediate access to the list of 2-D and 3-D neighbors (also called "Similar Compounds" and "Similar Conformers", respectively) for each compound in PubChem. However, because 3-D neighboring is much more time-consuming than 2-D neighboring, how different the results of the two neighboring schemes are is an important question, considering limited computational resources.
Results: The present study analyzed the complementarity between the PubChem 2-D and 3-D neighbors. When all compounds in PubChem were considered, the overlap between 2-D and 3-D neighbors was only 2% of the total neighbors. For the data sets containing compounds with annotated information, the overlap increased as the data sets became smaller. However, it did not exceed 31% and substantial fractions of neighbors were still recognized by either PubChem 2-D or 3-D similarity, but not by both. The Neighbor Preference Index (NPI) of a molecule for a given data set was introduced, which quantified whether a molecule had more 2-D or 3-D neighbors in the data set. The NPI histogram for all PubChem compounds had a bimodal shape with two maxima at NPI = +/- 1 and a minimum at NPI = 0. However, the NPI histograms for the subsets containing compounds with annotated information had a greater fraction of compounds with a strong preference for one neighboring method to the other (at NPI = +/- 1) as well as compounds with a neutral preference (at NPI = 0).
Conclusion: The results of our study indicate that, for the majority of the compounds in PubChem, their structural similarity to other compounds can be recognized predominantly by either 2-D or 3-D neighborings, but not by both, showing a strong complementarity between 2-D and 3-D neighboring results. Therefore, despite its heavy requirements for computational resources, 3-D neighboring provides an alternative way in which the user can instantly access structurally similar molecules that cannot be detected if only 2-D neighboring is used.
C1 [Kim, Sunghwan; Bolton, Evan E.; Bryant, Stephen H.] Natl Lib Med, Natl Ctr Biotechnol Informat, Dept Hlth & Human Serv, NIH, 8600 Rockville Pike, Bethesda, MD 20894 USA.
RP Kim, S (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, Dept Hlth & Human Serv, NIH, 8600 Rockville Pike, Bethesda, MD 20894 USA.
EM kimsungh@ncbi.nlm.nih.gov
RI Kim, Sunghwan/A-6738-2008
OI Kim, Sunghwan/0000-0001-9828-2074
FU Intramural Research Program of the National Library of Medicine,
National Institutes of Health, U.S. Department of Health and Human
Services
FX We are grateful to the NCBI Systems staff, especially Ron Patterson,
Charlie Cook, and Don Preuss, whose efforts helped make the PubChem3D
project possible. We also thank Cindy Clark, NIH Library Editing
Service, for reviewing the manuscript. This research was supported by
the Intramural Research Program of the National Library of Medicine,
National Institutes of Health, U.S. Department of Health and Human
Services.
NR 35
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U1 3
U2 3
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1758-2946
J9 J CHEMINFORMATICS
JI J. Cheminformatics
PD NOV 4
PY 2016
VL 8
AR 62
DI 10.1186/s13321-016-0163-1
PG 17
WC Chemistry, Multidisciplinary; Computer Science, Information Systems;
Computer Science, Interdisciplinary Applications
SC Chemistry; Computer Science
GA EB1DJ
UT WOS:000387086800002
PM 27872662
ER
PT J
AU Goodyear, K
Parasuraman, R
Chernyak, S
Madhavan, P
Deshpande, G
Krueger, F
AF Goodyear, Kimberly
Parasuraman, Raja
Chernyak, Sergey
Madhavan, Poornima
Deshpande, Gopikrishna
Krueger, Frank
TI Advice Taking from Humans and Machines: An fMRI and Effective
Connectivity Study
SO FRONTIERS IN HUMAN NEUROSCIENCE
LA English
DT Article
DE expert advice; functional magnetic resonance imaging (fMRI); effective
connectivity; Granger causality; precuneus; posterior insula
ID GRANGER CAUSALITY ANALYSIS; ROSTROLATERAL PREFRONTAL CORTEX;
DECISION-MAKING; INDIVIDUAL-DIFFERENCES; SOCIAL COGNITION; DETECTION
TASK; EXPERT ADVICE; BRAIN; TRUST; SYSTEMS
AB With new technological advances, advice can come from different sources such as machines or humans, but how individuals respond to such advice and the neural correlates involved need to be better understood. We combined functional MRI and multivariate Granger causality analysis with an X-ray luggage-screening task to investigate the neural basis and corresponding effective connectivity involved with advice utilization from agents framed as experts. Participants were asked to accept or reject good or bad advice from a human or machine agent with low reliability (high false alarm rate). We showed that unreliable advice decreased performance overall and participants interacting with the human agent had a greater depreciation of advice utilization during bad advice compared to the machine agent. These differences in advice utilization can be perceivably due to reevaluation of expectations arising from association of dispositional credibility for each agent. We demonstrated that differences in advice utilization engaged brain regions that may be associated with evaluation of personal characteristics and traits (precuneus, posterior cingulate cortex, temporoparietal junction) and interoception (posterior insula). We found that the right posterior insula and left precuneus were the drivers of the advice utilization network that were reciprocally connected to each other and also projected to all other regions. Our behavioral and neuroimaging results have significant implications for society because of progressions in technology and increased interactions with machines.
C1 [Goodyear, Kimberly] Brown Univ, Dept Behav & Social Sci, Ctr Alcohol & Addict Studies, Providence, RI 02912 USA.
[Goodyear, Kimberly] NIAAA, Sect Clin Psychoneuroendocrinol & Neuropsychophar, Bethesda, MD USA.
[Goodyear, Kimberly] NIDA, Bethesda, MD 20892 USA.
[Parasuraman, Raja; Krueger, Frank] George Mason Univ, Dept Psychol, Fairfax, VA 22030 USA.
[Chernyak, Sergey; Krueger, Frank] George Mason Univ, Mol Neurosci Dept, Fairfax, VA 22030 USA.
[Madhavan, Poornima] Inst Def Anal, Alexandria, VA USA.
[Deshpande, Gopikrishna] Auburn Univ, Dept Elect & Comp Engn, MRI Res Ctr, Auburn, AL 36849 USA.
[Deshpande, Gopikrishna] Auburn Univ, Dept Psychol, Auburn, AL 36849 USA.
[Deshpande, Gopikrishna] Auburn Univ, Alabama Adv Imaging Consortium, Birmingham, AL USA.
[Deshpande, Gopikrishna] Univ Alabama Birmingham, Birmingham, AL USA.
RP Krueger, F (reprint author), George Mason Univ, Dept Psychol, Fairfax, VA 22030 USA.; Krueger, F (reprint author), George Mason Univ, Mol Neurosci Dept, Fairfax, VA 22030 USA.
EM fkrueger@gmu.edu
OI Deshpande, Gopikrishna/0000-0001-7471-5357
FU Air Force of Scientific Research [202857]
FX This work was supported by the Air Force of Scientific Research
[202857].
NR 102
TC 0
Z9 0
U1 14
U2 14
PU FRONTIERS MEDIA SA
PI LAUSANNE
PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015,
SWITZERLAND
SN 1662-5161
J9 FRONT HUM NEUROSCI
JI Front. Hum. Neurosci.
PD NOV 4
PY 2016
VL 10
AR 542
DI 10.3389/fnhum.2016.00542
PG 15
WC Neurosciences; Psychology
SC Neurosciences & Neurology; Psychology
GA EA9IF
UT WOS:000386955600001
PM 27867351
ER
PT J
AU Park, T
Chen, HZ
Kevala, K
Lee, JW
Kim, HY
AF Park, Taeyeop
Chen, Huazhen
Kevala, Karl
Lee, Ji-Won
Kim, Hee-Yong
TI N-Docosahexaenoylethanolamine ameliorates LPS-induced neuroinflammation
via cAMP/PKA-dependent signaling
SO JOURNAL OF NEUROINFLAMMATION
LA English
DT Article
DE Synaptamide; Microglia; NF-kappa B; Docosahexaenoic acid; Cytokine;
iNOS; CCL2; Iba-1; GFAP; FAA
ID NITRIC-OXIDE SYNTHASE; TUMOR-NECROSIS-FACTOR; KAPPA-B; TRANSCRIPTIONAL
ACTIVITY; PROSTAGLANDIN E-2; CELL ACTIVATION; NERVOUS-SYSTEM; BRAIN;
MICROGLIA; LIPOPOLYSACCHARIDE
AB Background: Brain inflammation has been implicated as a critical mechanism responsible for the progression of neurodegeneration and characterized by glial cell activation accompanied by production of inflammation-related cytokines and chemokines. Growing evidence also suggests that metabolites derived from docosahexaenoic acid (DHA) have anti-inflammatory and pro-resolving effects; however, the possible role of N-docosahexaenoylethanolamine (synaptamide), an endogenous neurogenic and synaptogenic metabolite of DHA, in inflammation, is largely unknown. (The term "synaptamide" instead of "DHEA" was used for N-docosahexaenoylethanolamine since DHEA is a widely used and accepted term for the steroid, dehydroepiandrosterone.) In the present study, we tested this possibility using a lipopolysaccharide (LPS)-induced neuroinflammation model both in vitro and in vivo.
Methods: For in vitro studies, we used P3 primary rat microglia and immortalized murine microglia cells (BV2) to assess synaptamide effects on LPS-induced cytokine/chemokine/iNOS (inducible nitric oxide synthase) expression by quantitative PCR (qPCR) and enzyme-linked immunosorbent assay (ELISA). To evaluate in vivo effects, mice were intraperitoneally (i.p.) injected with LPS followed by synaptamide, and expression of proinflammatory mediators was measured by qPCR and western blot analysis. Activation of microglia and astrocyte in the brain was examined by Iba-1 and GFAP immunostaining.
Results: Synaptamide significantly reduced LPS-induced production of TNF-alpha and NO in cultured microglia cells. Synaptamide increased intracellular cAMP levels, phosphorylation of PKA, and phosphorylation of CREB but suppressed LPS-induced nuclear translocation of NF-kappa B p65. Conversely, adenylyl cyclase or PKA inhibitors abolished the synaptamide effect on p65 translocation as well as TNF-alpha and iNOS expression. Administration of synaptamide following LPS injection (i.p.) significantly reduced neuroinflammatory responses, such as microglia activation and mRNA expression of inflammatory cytokines, chemokine, and iNOS in the brain.
Conclusions: DHA-derived synaptamide is a potent suppressor of neuroinflammation in an LPS-induced model, by enhancing cAMP/PKA signaling and inhibiting NF-kappa B activation. The anti-inflammatory capability of synaptamide may provide a new therapeutic avenue to ameliorate the inflammation-associated neurodegenerative conditions.
C1 [Park, Taeyeop; Chen, Huazhen; Kevala, Karl; Lee, Ji-Won; Kim, Hee-Yong] NIAAA, Mol Signalling Lab, NIH, 5625 Fishers Lane, Rockville, MD 20852 USA.
[Kim, Hee-Yong] NIAAA, NIH, 5625 Fishers Lane,Rm 3N-07, Bethesda, MD 20892 USA.
RP Kim, HY (reprint author), NIAAA, Mol Signalling Lab, NIH, 5625 Fishers Lane, Rockville, MD 20852 USA.; Kim, HY (reprint author), NIAAA, NIH, 5625 Fishers Lane,Rm 3N-07, Bethesda, MD 20892 USA.
EM hykim@nih.gov
FU Intramural Research Program of the National Institute of Alcohol Abuse
and Alcoholism, National Institutes of Health
FX This study was funded by the Intramural Research Program of the National
Institute of Alcohol Abuse and Alcoholism, National Institutes of
Health. The funding agencies did not participate in planning the
experiments, data analysis, or preparing the manuscript.
NR 53
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U1 4
U2 4
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1742-2094
J9 J NEUROINFLAMM
JI J. Neuroinflamm.
PD NOV 4
PY 2016
VL 13
AR 284
DI 10.1186/s12974-016-0751-z
PG 15
WC Immunology; Neurosciences
SC Immunology; Neurosciences & Neurology
GA EB1DO
UT WOS:000387087600001
PM 27809877
ER
PT J
AU Tripathi, V
Sixt, KM
Gao, SJ
Xu, X
Huang, J
Weigert, R
Zhou, M
Zhang, YE
AF Tripathi, Veenu
Sixt, Katherine M.
Gao, Shaojian
Xu, Xuan
Huang, Jing
Weigert, Roberto
Zhou, Ming
Zhang, Ying E.
TI Direct Regulation of Alternative Splicing by SMAD3 through PCBP1 Is
Essential to the Tumor-Promoting Role of TGF-beta
SO MOLECULAR CELL
LA English
DT Article
ID EPITHELIAL-MESENCHYMAL TRANSITION; CANCER PROGRESSION; TRANSCRIPTION;
METASTASIS; PHOSPHORYLATION; ASSOCIATION; TRANSLATION; EXPRESSION;
PATHWAYS; CD44
AB In advanced stages of cancers, TGF-beta promotes tumor progression in conjunction with inputs from receptor tyrosine kinase pathways. However, mechanisms that underpin the signaling cooperation and convert TGF-beta from a potent growth inhibitor to a tumor promoter are not fully understood. We report here that TGF-beta directly regulates alternative splicing of cancer stem cell marker CD44 through a phosphorylated T179 of SMAD3-mediated interaction with RNA-binding protein PCBP1. We show that TGF-beta and EGF respectively induce SMAD3 and PCBP1 to colocalize in SC35-positive nuclear speckles, and the two proteins interact in the variable exon region of CD44 pre-mRNA to inhibit spliceosome assembly in favor of expressing the mesenchymal isoform CD44s over the epithelial isoform CD44E. We further show that the SMAD3-mediated alternative splicing is essential to the tumor-promoting role of TGF-beta and has a global influence on protein products of genes instrumental to epithelial-to-mesenchymal transition and metastasis.
C1 [Tripathi, Veenu; Sixt, Katherine M.; Xu, Xuan; Weigert, Roberto; Zhang, Ying E.] NCI, Lab Cellular & Mol Biol, Ctr Canc Res, Bethesda, MD 20892 USA.
[Gao, Shaojian] NCI, Genet Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Huang, Jing] NCI, Lab Canc Biol & Genet, Ctr Canc Res, Bethesda, MD 20892 USA.
[Zhou, Ming] Leidos Biomed Res Inc, Lab Prot Characterizat, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
RP Zhang, YE (reprint author), NCI, Lab Cellular & Mol Biol, Ctr Canc Res, Bethesda, MD 20892 USA.
EM zhangyin@mail.nih.gov
RI Zhang, Ying/G-3657-2015
OI Zhang, Ying/0000-0003-2753-7601
FU NIH, National Cancer Institute, Center for Cancer Research
FX We thank Drs. B. O'Malley and R. Kumar for PCBP1 plasmids, Jing Yang for
HMLE cells, Chonghui Cheng for the CD44v plasmid, and Fang Liu for SMAD3
pT208 antibodies. This research was supported by the intramural research
program of the NIH, National Cancer Institute, Center for Cancer
Research.
NR 35
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U1 3
U2 3
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1097-2765
EI 1097-4164
J9 MOL CELL
JI Mol. Cell
PD NOV 3
PY 2016
VL 64
IS 3
BP 549
EP 564
DI 10.1016/j.molcel.2016.09.013
PG 16
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA EE3RQ
UT WOS:000389515300013
PM 27746021
ER
PT J
AU Ren, JQ
Stroncek, DF
AF Ren, Jiaqiang
Stroncek, David F.
TI Gene therapy simplified
SO BLOOD
LA English
DT Editorial Material
C1 [Ren, Jiaqiang; Stroncek, David F.] NIH, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA.
RP Ren, JQ (reprint author), NIH, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA.
NR 10
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA
SN 0006-4971
EI 1528-0020
J9 BLOOD
JI Blood
PD NOV 3
PY 2016
VL 128
IS 18
BP 2194
EP 2195
DI 10.1182/blood-2016-09-736983
PG 4
WC Hematology
SC Hematology
GA EC4LA
UT WOS:000388099600002
PM 27811188
ER
PT J
AU Goldin, LR
McMaster, ML
Rotunno, M
Herman, SEM
Jones, K
Zhu, B
Boland, J
Burdett, L
Hicks, B
Ravichandran, S
Luke, BT
Yeager, M
Fontaine, L
Goldstein, AM
Chanock, SJ
Tucker, MA
Wiestner, A
Marti, G
Caporaso, NE
AF Goldin, Lynn R.
McMaster, Mary L.
Rotunno, Melissa
Herman, Sarah E. M.
Jones, Kristine
Zhu, Bin
Boland, Joseph
Burdett, Laurie
Hicks, Belynda
Ravichandran, Sarangan
Luke, Brian T.
Yeager, Meredith
Fontaine, Laura
Goldstein, Alisa M.
Chanock, Stephen J.
Tucker, Margaret A.
Wiestner, Adrian
Marti, Gerald
Caporaso, Neil E.
TI Whole exome sequencing in families with CLL detects a variant in
Integrin beta 2 associated with disease susceptibility
SO BLOOD
LA English
DT Letter
ID CHRONIC LYMPHOCYTIC-LEUKEMIA; LYMPHOPROLIFERATIVE DISORDERS; EXPRESSION;
RISK
C1 [Goldin, Lynn R.; McMaster, Mary L.; Goldstein, Alisa M.; Caporaso, Neil E.] NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Rotunno, Melissa] NCI, Epidemiol & Genom Res Program, Div Canc Control & Populat Sci, NIH, Bethesda, MD 20892 USA.
[Herman, Sarah E. M.; Wiestner, Adrian] NHLBI, Hematol Branch, NIH, Bldg 10, Bethesda, MD 20892 USA.
[Jones, Kristine; Zhu, Bin; Boland, Joseph; Burdett, Laurie; Hicks, Belynda; Yeager, Meredith] NCI, Canc Genom Res Lab, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Ravichandran, Sarangan; Luke, Brian T.] Frederick Natl Lab Canc Res, Adv Biomed Comp Ctr, Frederick, MD USA.
[Fontaine, Laura] Westat Corp, Rockville, MD USA.
[Chanock, Stephen J.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Tucker, Margaret A.] NCI, Human Genet Program, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Marti, Gerald] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA.
RP Goldin, LR (reprint author), NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, 9609 Med Ctr Dr,Rm 6E432, Bethesda, MD 20892 USA.
EM goldinl@mail.nih.gov
NR 13
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U1 1
U2 1
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA
SN 0006-4971
EI 1528-0020
J9 BLOOD
JI Blood
PD NOV 3
PY 2016
VL 128
IS 18
BP 2261
EP 2263
DI 10.1182/blood-2016-02-697771
PG 3
WC Hematology
SC Hematology
GA EC4LA
UT WOS:000388099600011
PM 27629550
ER
PT J
AU Ngwa, JS
Cabral, HJ
Cheng, DM
Pencina, MJ
Gagnon, DR
LaValley, MP
Cupples, LA
AF Ngwa, Julius S.
Cabral, Howard J.
Cheng, Debbie M.
Pencina, Michael J.
Gagnon, David R.
LaValley, Michael P.
Cupples, L. Adrienne
TI A comparison of time dependent Cox regression, pooled logistic
regression and cross sectional pooling with simulations and an
application to the Framingham Heart Study
SO BMC MEDICAL RESEARCH METHODOLOGY
LA English
DT Article
DE Time dependent covariate model (TDCM); Cross sectional pooling (CSP);
Pooled logistic regression (PLR); Longitudinal and survival data
ID PROPORTIONAL-HAZARDS; ATRIAL-FIBRILLATION; SURVIVAL ANALYSIS; AGE;
WOMEN; SCORE; MODEL
AB Background: Typical survival studies follow individuals to an event and measure explanatory variables for that event, sometimes repeatedly over the course of follow up. The Cox regression model has been used widely in the analyses of time to diagnosis or death from disease. The associations between the survival outcome and time dependent measures may be biased unless they are modeled appropriately.
Methods: In this paper we explore the Time Dependent Cox Regression Model (TDCM), which quantifies the effect of repeated measures of covariates in the analysis of time to event data. This model is commonly used in biomedical research but sometimes does not explicitly adjust for the times at which time dependent explanatory variables are measured. This approach can yield different estimates of association compared to a model that adjusts for these times. In order to address the question of how different these estimates are from a statistical perspective, we compare the TDCM to Pooled Logistic Regression (PLR) and Cross Sectional Pooling (CSP), considering models that adjust and do not adjust for time in PLR and CSP.
Results: In a series of simulations we found that time adjusted CSP provided identical results to the TDCM while the PLR showed larger parameter estimates compared to the time adjusted CSP and the TDCM in scenarios with high event rates. We also observed upwardly biased estimates in the unadjusted CSP and unadjusted PLR methods. The time adjusted PLR had a positive bias in the time dependent Age effect with reduced bias when the event rate is low. The PLR methods showed a negative bias in the Sex effect, a subject level covariate, when compared to the other methods. The Cox models yielded reliable estimates for the Sex effect in all scenarios considered.
Conclusions: We conclude that survival analyses that explicitly account in the statistical model for the times at which time dependent covariates are measured provide more reliable estimates compared to unadjusted analyses. We present results from the Framingham Heart Study in which lipid measurements and myocardial infarction data events were collected over a period of 26 years.
C1 [Ngwa, Julius S.; Cabral, Howard J.; Cheng, Debbie M.; Gagnon, David R.; LaValley, Michael P.; Cupples, L. Adrienne] Boston Univ, Sch Publ Hlth, Dept Biostat, 801 Massachusetts Ave,CT 3rd Floor, Boston, MA 02118 USA.
[Ngwa, Julius S.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Biostat, 615 N Wolfe St, Baltimore, MD 21205 USA.
[Pencina, Michael J.] Duke Univ, Sch Med, Dept Biostat & Bioinformat, 2400 Pratt St,7021 North Pavil, Durham, NC 27705 USA.
[Cupples, L. Adrienne] NHLBI, Framingham Heart Study, Framingham, MA 01702 USA.
RP Ngwa, JS; Cupples, LA (reprint author), Boston Univ, Sch Publ Hlth, Dept Biostat, 801 Massachusetts Ave,CT 3rd Floor, Boston, MA 02118 USA.
EM ngwaj@bu.edu; adrienne@bu.edu
FU National Heart, Lung and Blood Institute's Framingham Heart Study of the
National Institutes of Health [N01-HC-25195, HHSN268201500001I]; Boston
University School of Medicine; National Center for Research Resources
(NIH NCRR)
FX This work was supported by the National Heart, Lung and Blood
Institute's Framingham Heart Study (Contracts N01-HC-25195 and
HHSN268201500001I) of the National Institutes of Health and Boston
University School of Medicine. A portion of this research was conducted
using Boston University Linux Cluster for Genetic Analysis (LinGA)
funded by the National Center for Research Resources (NIH NCRR).
NR 28
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U1 3
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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 NOV 3
PY 2016
VL 16
AR 148
DI 10.1186/s12874-016-0248-6
PG 12
WC Health Care Sciences & Services
SC Health Care Sciences & Services
GA EC2FT
UT WOS:000387925800001
PM 27809784
ER
PT J
AU Guan, B
Welch, JM
Sapp, JC
Ling, H
Li, YL
Johnston, JJ
Kebebew, E
Biesecker, LG
Simonds, WF
Marx, SJ
Agarwal, SK
AF Guan, Bin
Welch, James M.
Sapp, Julie C.
Ling, Hua
Li, Yulong
Johnston, Jennifer J.
Kebebew, Electron
Biesecker, Leslie G.
Simonds, William F.
Marx, Stephen J.
Agarwal, Sunita K.
TI GCM2-Activating Mutations in Familial Isolated Hyperparathyroidism
SO AMERICAN JOURNAL OF HUMAN GENETICS
LA English
DT Article
ID ASYMPTOMATIC PRIMARY HYPERPARATHYROIDISM; AUTOSOMAL-DOMINANT
HYPOPARATHYROIDISM; PARATHYROID-GLAND DEVELOPMENT;
CELLS-MISSING-HOMOLOG; TRANSCRIPTION FACTOR; GCMB MUTATION; GENE;
HORMONE; EXPRESSION; MANAGEMENT
AB Primary hyperparathyroidism (PHPT) is a common endocrine disease characterized by parathyroid hormone excess and hypercalcemia and caused by hypersecreting parathyroid glands. Familial PHPT occurs in an isolated nonsyndromal form, termed familial isolated hyperparathyroidism (FIHP), or as part of a syndrome, such as multiple endocrine neoplasia type 1 or hyperparathyroidism-jaw tumor syndrome. The specific genetic or other cause(s) of FIHP are unknown. We performed exome sequencing on germline DNA of eight index-case individuals from eight unrelated kindreds with FIHP. Selected rare variants were assessed for co-segregation in affected family members and screened for in an additional 32 kindreds with FIHP. In eight kindreds with FIHP, we identified three rare missense variants in GCM2, a gene encoding a transcription factor required for parathyroid development. Functional characterization of the GCM2 variants and deletion analyses revealed a small C-terminal conserved inhibitory domain (CCID) in GCM2. Two of the three rare variants were recurrent, located in the GCM2 CCID, and found in seven of the 40 (18%) kindreds with FIHP. These two rare variants acted as gain-of-function mutations that increased the transcriptional activity of GCM2, suggesting that GCM2 is a parathyroid proto-oncogene. Our results demonstrate that germline-activating mutations affecting the CCID of GCM2 can cause FIHP.
C1 [Guan, Bin; Welch, James M.; Li, Yulong; Simonds, William F.; Marx, Stephen J.; Agarwal, Sunita K.] Natl Inst Diabet & Digest & Kidney Dis, Bethesda, MD 20892 USA.
[Sapp, Julie C.; Johnston, Jennifer J.; Biesecker, Leslie G.] NHGRI, Bethesda, MD 20892 USA.
[Ling, Hua] Johns Hopkins Univ, Ctr Inherited Dis Res, Baltimore, MD 21224 USA.
[Kebebew, Electron] NCI, Bethesda, MD 20892 USA.
[Marx, Stephen J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD 20892 USA.
RP Guan, B; Agarwal, SK (reprint author), Natl Inst Diabet & Digest & Kidney Dis, Bethesda, MD 20892 USA.
EM bin.guan@nih.gov; sunitaa@mail.nih.gov
RI Agarwal, Sunita/D-1428-2016
OI Agarwal, Sunita/0000-0002-7557-3191
FU NIH; NIDDK; National Human Genome Research Institute; Eunice Kennedy
Shriver National Institute of Child Health and Human Development;
National Cancer Institute
FX The authors are grateful to the participants in this study. We thank
members at the National Institute of Diabetes and Digestive and Kidney
Diseases (NIDDK) Clinical Laboratory Core for storage of DNA samples. We
would like to thank Mr. Craig Cochran and the NIH 5NW nursing staff for
their expert patient care. We also thank our colleagues Drs. Lee
Weinstein, Monica Skarulis, and Michael Collins, as well as the past and
present fellows of the National Institute of Child Health and Human
Development (NICHD)-NIDDK Interinstitute Endocrine Training Program.
This work was supported by the Intramural Research Program of the NIH,
the NIDDK (S.J.M., S.K.A., and W.F.S.), the National Human Genome
Research Institute (L.G.B., J.C.S., and J.J.J.), the Eunice Kennedy
Shriver National Institute of Child Health and Human Development
(S.J.M.), and the National Cancer Institute (E.K.).
NR 42
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U1 0
U2 0
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0002-9297
EI 1537-6605
J9 AM J HUM GENET
JI Am. J. Hum. Genet.
PD NOV 3
PY 2016
VL 99
IS 5
BP 1034
EP 1044
DI 10.1016/j.ajhg.2016.08.018
PG 11
WC Genetics & Heredity
SC Genetics & Heredity
GA EB6XT
UT WOS:000387529600003
PM 27745835
ER
PT J
AU O'Grady, GL
Best, HA
Sztal, TE
Schartner, V
Sanjuan-Vazquez, T
Donkervoort, S
Neto, OA
Sutton, RB
Ilkovski, B
Romero, NB
Stojkovic, T
Dastgir, J
Waddell, LB
Boland, A
Hu, Y
Williams, C
Ruparelia, AA
Maisonobe, T
Peduto, AJ
Reddel, SW
Lek, M
Tukiainen, T
Cummings, BB
Joshi, H
Nectoux, J
Brammah, S
Deleuze, JF
Ing, VO
Ramm, G
Ardicli, D
Nowak, KJ
Talim, B
Topaloglu, H
Laing, NG
North, KN
MacArthur, DG
Friant, S
Clarke, NF
Bryson-Richardson, RJ
Bonnemann, CG
Laporte, J
Cooper, ST
AF O'Grady, Gina L.
Best, Heather A.
Sztal, Tamar E.
Schartner, Vanessa
Sanjuan-Vazquez, Tvlyriam
Donkervoort, Sandra
Neto, Osorio Abath
Sutton, Roger Bryan
Ilkovski, Biljana
Romero, Norma Beatriz
Stojkovic, Tanya
Dastgir, Jahannaz
Waddell, Leigh B.
Boland, Anne
Hu, Ying
Williams, Caitlin
Ruparelia, Avnika A.
Maisonobe, Thierry
Peduto, Anthony J.
Reddel, Stephen W.
Lek, Monkol
Tukiainen, Tam
Cummings, Beryl B.
Joshi, Himanshu
Nectoux, Juliette
Brammah, Susan
Deleuze, Jean-Francois
Ing, Viola Oorschot
Ramm, Georg
Ardicli, Didem
Nowak, Kristen J.
Talim, Beril
Topaloglu, Haluk
Laing, Nigel G.
North, Kathryn N.
MacArthur, Daniel G.
Friant, Sylvie
Clarke, Nigel F.
Bryson-Richardson, Robert J.
Bonnemann, Carsten G.
Laporte, Jocelyn
Cooper, Sandra T.
TI Variants in the Oxidoreductase PYROXD1 Cause Early-Onset Myopathy with
Internalized Nuclei and Myofibrillar Disorganization
SO AMERICAN JOURNAL OF HUMAN GENETICS
LA English
DT Article
ID CONGENITAL MYOPATHIES; PHYLOGENETIC ANALYSIS; NEMALINE MYOPATHY;
ZEBRAFISH MODELS; GENETIC-VARIANTS; GENERATION; DIAGNOSIS; DISEASE;
MUSCLE
AB This study establishes PYROXD1 variants as a cause of early-onset myopathy and uses biospecimens and cell lines, yeast, and zebrafish models to elucidate the fundamental role of PYROXD1 in skeletal muscle. Exome sequencing identified recessive variants in PYROXD1 in nine probands from five families. Affected individuals presented in infancy or childhood with slowly progressive proximal and distal weakness, facial weakness, nasal speech, swallowing difficulties, and normal to moderately elevated creatine kinase. Distinctive histopathology showed abundant internalized nuclei, myofibrillar disorganization, desmin-positive inclusions, and thickened Z-bands. PYROXD1 is a nuclear-cytoplasmic pyridine nucleotide-disulphide reductase (PNDR). PNDRs are flavoproteins (FAD-binding) and catalyze pyridine-nucleotide-dependent (NAD/NADH) reduction of thiol residues in other proteins. Complementation experiments in yeast lacking glutathione reductase girl show that human PYROXD1 has reductase activity that is strongly impaired by the disease-associated missense mutations. Immunolocalization studies in human muscle and zebrafish myofibers demonstrate that PYROXD1 localizes to the nucleus and to striated sarcomeric compartments. Zebrafish with ryroxD1 knock-down recapitulate features of PYROXD1 myopathy with sarcomeric disorganization, myofibrillar aggregates, and marked swimming defect. We characterize variants in the oxidoreductase PYROXD1 as a cause of early-onset myopathy with distinctive histopathology and introduce altered redox regulation as a primary cause of congenital muscle disease.
C1 [O'Grady, Gina L.; Best, Heather A.; Ilkovski, Biljana; Waddell, Leigh B.; Joshi, Himanshu; North, Kathryn N.; Clarke, Nigel F.; Cooper, Sandra T.] Childrens Hosp Westmead, Kids Res Inst, Inst Neurosci & Muscle Res, Sydney, NSW 2145, Australia.
[O'Grady, Gina L.; Best, Heather A.; Clarke, Nigel F.; Cooper, Sandra T.] Univ Sydney, Discipline Paediat & Child Hlth, Fac Med, Sydney, NSW 2006, Australia.
[O'Grady, Gina L.] Starship Childrens Hlth, Paediat Neurol Serv, Auckland 1023, New Zealand.
[Sztal, Tamar E.; Williams, Caitlin; Ruparelia, Avnika A.; Bryson-Richardson, Robert J.] Monash Univ, Sch Biol Sci, Melbourne, Vic 3800, Australia.
[Schartner, Vanessa; Neto, Osorio Abath; Laporte, Jocelyn] IGBMC, F-67400 Illkirch Graffenstaden, France.
[Sanjuan-Vazquez, Tvlyriam; Friant, Sylvie] Univ Strasbourg, CNRS, UMR7156, Dept Mol & Cellular Genet, F-67081 Strasbourg, France.
[Donkervoort, Sandra; Dastgir, Jahannaz; Hu, Ying; Bonnemann, Carsten G.] NINDS, Neurogenet Branch, Neuromuscular & Neurogenet Disorders Childhood Se, NIH, Bethesda, MD 20892 USA.
[Sutton, Roger Bryan] Texas Tech Univ, Hlth Sci Ctr, Dept Cell Physiol & Mol Biophys, Lubbock, TX 79430 USA.
[Sutton, Roger Bryan] Texas Tech Univ, Hlth Sci Ctr, Ctr Membrane Prot Res, Lubbock, TX 79430 USA.
[Romero, Norma Beatriz] UPMC Univ Paris 06, INSERM, UMRS974,CNRS FRE3617, Sorbonne Univ,Ctr Res Myol,GH Pitie Salpetriere, 47 Blvd Hop, F-75013 Paris, France.
[Romero, Norma Beatriz; Stojkovic, Tanya; Maisonobe, Thierry] GHU La Pitie Salpetriere, AP HP, Inst Myol, Ctr Reference Pathol Neuromusculaire Paris Est, F-7503 Paris, France.
[Boland, Anne; Deleuze, Jean-Francois] CEA, Ctr Natl Genotypage, Inst Genom, CP5721, F-91057 Evry, France.
[Peduto, Anthony J.] Univ Sydney, Dept Radiol, Westmead Hosp, Western Clin Sch, Sydney, NSW 1024, Australia.
[Reddel, Stephen W.] Univ Sydney, Concord Clin Sch, Dept Neurol, Sydney, NSW 2139, Australia.
[Lek, Monkol; Tukiainen, Tam; Cummings, Beryl B.; MacArthur, Daniel G.] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA.
[Lek, Monkol; Tukiainen, Tam; Cummings, Beryl B.; MacArthur, Daniel G.] Broad Inst Harvard & Massachusetts Inst Technol, Cambridge, MA 02142 USA.
[Nectoux, Juliette] HUPC Hop Cochin, Serv Biochim & Genet Mol, F-75014 Paris, France.
[Nectoux, Juliette] Univ Paris 05, INSERM, U1016, Inst Cochin,CNRS UMR8104, F-75014 Paris, France.
[Brammah, Susan] Concord Repatriat Gen Hosp, Electron Microscope Unit, Concord, NSW 2139, Australia.
[Ing, Viola Oorschot; Ramm, Georg] Monash Univ, Clive & Vera Ramaciotti Ctr Struct Cryoelectron M, Melbourne, Vic 3800, Australia.
[Ramm, Georg] Monash Univ, Dept Biochem & Mol Biol, Melbourne, Vic 3800, Australia.
[Ardicli, Didem; Talim, Beril; Topaloglu, Haluk] Hacettepe Univ, Dept Pediat Neurol, Childrens Hosp, TR-06100 Ankara, Turkey.
[Nowak, Kristen J.; Laing, Nigel G.] Univ Western Australia, Ctr Med Res, Perth, WA 6009, Australia.
[Nowak, Kristen J.; Laing, Nigel G.] Harry Perkins Inst Med Res, Perth, WA 6009, Australia.
[North, Kathryn N.] Royal Childrens Hosp, Murdoch Childrens Res Inst, Flemington Rd, Parkville, Vic 3052, Australia.
[Laporte, Jocelyn] Univ Strasbourg, F-67081 Illkirch Graffenstaden, France.
RP Cooper, ST (reprint author), Childrens Hosp Westmead, Kids Res Inst, Inst Neurosci & Muscle Res, Sydney, NSW 2145, Australia.; Cooper, ST (reprint author), Univ Sydney, Discipline Paediat & Child Hlth, Fac Med, Sydney, NSW 2006, Australia.
EM sandra.cooper@sydney.edu.au
RI North, Kathryn/K-6476-2012;
OI North, Kathryn/0000-0003-0841-8009; Friant, Sylvie/0000-0002-5412-6288
FU Australian National Health and Medical Research Council (NHMRC)
[1080587, 1022707, 1031893, 1048816, 1056285]; Muscular Dystrophy New
South Wales; Royal Australasian College of Physicians; Australian
Research Council [FT100100734]; National Human Genome Research Institute
of the NIH [U54 HG003067]; Division of Intramural Research of the
National Institutes of Neurological Disorders and Stroke, France
Genomique National infrastructure grant Investissements d'Avenir and
Agence Nationale pour la Recherche [ANR-10-INBS-09, ANR-11-BSV1-026];
Fondation Maladies Rares "Myocapture" sequencing project; Association
Frangaise contre les Myopathies [AFM-15352, AFM-16551]; Muscular
Dystrophy Association [MDA-186985]; Myotubular Trust; IDEX-Universite de
Strasbourg PhD fellowship; NINDS/NIH
FX This study was supported by the following funding: The Australian
National Health and Medical Research Council (NHMRC) 1080587 (S.T.C.,
N.F.C., D.G.M., K.N.N., R.B.R., K.J.N., N.G.L.), 1022707 and 1031893
(K.N.N., N.F.C., and N.G.L.), 1048816 (S.T.C.), and 1056285 (G.L.O.),
Muscular Dystrophy New South Wales (G.L.O.), Royal Australasian College
of Physicians (G.L.O.), Australian Research Council FT100100734
(K.J.N.), National Human Genome Research Institute of the NIH (D.G.M.,
Medical Sequencing Program grant U54 HG003067 to the Broad Institute
principal investigator, Lander), Division of Intramural Research of the
National Institutes of Neurological Disorders and Stroke, France
Genomique National infrastructure grant Investissements d'Avenir and
Agence Nationale pour la Recherche (ANR-10-INBS-09 and ANR-11-BSV1-026),
Fondation Maladies Rares "Myocapture" sequencing project, Association
Frangaise contre les Myopathies (AFM-15352 and AFM-16551), Muscular
Dystrophy Association (MDA-186985), Myotubular Trust and IDEX-Universite
de Strasbourg PhD fellowship (M.S.-V), and intramural funds of the
NINDS/NIH (C.G.B. and S.D.).
NR 35
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PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0002-9297
EI 1537-6605
J9 AM J HUM GENET
JI Am. J. Hum. Genet.
PD NOV 3
PY 2016
VL 99
IS 5
BP 1086
EP 1105
DI 10.1016/j.ajhg.2016.09.005
PG 20
WC Genetics & Heredity
SC Genetics & Heredity
GA EB6XT
UT WOS:000387529600007
PM 27745833
ER
PT J
AU Rubio-Tapia, A
Ludvigsson, JF
Choung, RS
Brantner, TL
Rajkumar, SV
Landgren, O
Murray, JA
AF Rubio-Tapia, Alberto
Ludvigsson, Jonas F.
Choung, Rok Seon
Brantner, Tricia L.
Rajkumar, S. Vincent
Landgren, Ola
Murray, Joseph A.
TI Increased mortality among men aged 50 years old or above with elevated
IgA anti-transglutaminase antibodies: NHANES III
SO BMC GASTROENTEROLOGY
LA English
DT Article
DE Epidemiology; Survival; Transglutaminase
ID POPULATION-BASED COHORT; UNDIAGNOSED CELIAC-DISEASE; UNITED-STATES;
NATIONAL-HEALTH; INDIVIDUALS; PREVALENCE; MALIGNANCY; RISK
AB Background: Immunoglobulin A (IgA) antibodies to tissue transglutaminase (tTG) are the serologic test of choice for diagnosing celiac disease (CD). Our aim was to determine if elevated IgA anti-tTG were associated with increased mortality risk.
Methods: Stored serum samples of National Health and Nutrition Examination Survey (NHANES) III (1988-1992) were available for 6032 individuals aged 50 years old or above, which were screened for IgA anti-tTG, and if positive, for IgA endomysial antibodies. Mortality was determined from the National Death Index records through 2006. Hazard ratios were calculated through Cox proportional hazards regression.
Results: From a total of 6032, 85 participants tested positive for IgA anti-tTG (1.4 %) and 5947 tested negative. After a median follow-up of 13 years, IgA anti-tTG positive participants were at increased risk of death in both crude (HR = 1.68; 95 % CI = 1.30-2.18) and adjusted analyses (adjusted hazard ratio = 1.43; 95 % CI = 1.10-1.85) as compared to IgA anti-tTG negative participants. The excess mortality was restricted to IgA anti-tTG positive males (adjusted hazard ratio = 1.69 (95 % CI = 1.26-2.29), as opposed to a hazard ratio of 0.96 (95 % CI = 0.57-1.62) among IgA anti-tTG positive females. Although the most common cause of death in IgA anti-tTG positive participants was cardiovascular disease (36 %), the increased hazard ratio was only observed in respiratory cause of death as compared to IgA anti-tTG negative participants (adjusted hazard ratio = 5.11; 2.76-9.46).
Conclusion: Men aged 50 years old or above participants of NHANES III with elevated IgA anti-tTG antibodies had increased mortality risk. Elevated IgA anti-tTG antibodies could be a nonspecific marker of serious disease in older men.
C1 [Rubio-Tapia, Alberto; Choung, Rok Seon; Brantner, Tricia L.; Murray, Joseph A.] Mayo Clin, Div Gastroenterol & Hepatol, Dept Med, Rochester, MN 55905 USA.
[Ludvigsson, Jonas F.] Orebro Univ Hosp, Dept Pediat, Orebro, Sweden.
[Ludvigsson, Jonas F.] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
[Rajkumar, S. Vincent] Mayo Clin, Dept Med, Div Hematol, Rochester, MN USA.
[Landgren, Ola] NCI, Multiple Myeloma Sect, Lymphoid Malignancy Branch, NIH, Bethesda, MD 20892 USA.
[Landgren, Ola] Mem Sloan Kettering Canc Ctr, Dept Med, Myeloma Serv, 1275 York Ave, New York, NY 10021 USA.
[Landgren, Ola] NIDDK, NIH, US Dept HHS, Bethesda, MD 20892 USA.
RP Murray, JA (reprint author), Mayo Clin, Div Gastroenterol & Hepatol, Dept Med, Rochester, MN 55905 USA.
EM murray.joseph@mayo.edu
FU Centers for Disease Control and Prevention [M26561]; American College of
Gastroenterology Junior Faculty Development Award; Swedish Research
Council; Fulbright Commission
FX This work was supported by the Centers for Disease Control and
Prevention Contract #M26561 (J.A.M.), American College of
Gastroenterology Junior Faculty Development Award (A.R-T.), and the
Swedish Research Council and the Fulbright Commission (J.F.L.).
NR 24
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U1 3
U2 3
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-230X
J9 BMC GASTROENTEROL
JI BMC Gastroenterol.
PD NOV 3
PY 2016
VL 16
AR 136
DI 10.1186/s12876-016-0547-8
PG 6
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA EB7AK
UT WOS:000387537200001
PM 27809801
ER
PT J
AU Schmidt, T
Situ, AJ
Ulmer, TS
AF Schmidt, Thomas
Situ, Alan J.
Ulmer, Tobias S.
TI Direct Evaluation of Protein-Lipid Contacts Reveals Protein Membrane
Immersion and Isotropic Bicelle Structure
SO JOURNAL OF PHYSICAL CHEMISTRY LETTERS
LA English
DT Article
ID ALPHA-IIB-BETA-3 TRANSMEMBRANE COMPLEX; PHOSPHOLIPID BICELLES;
NMR-SPECTROSCOPY; MIXED MICELLES; DYNAMICS; BILAYERS; HELICES;
THREONINE; SEGMENT; MOTIFS
AB The solvation of membrane proteins by both lipids and water makes their membrane immersion difficult to predict and the choice of a membrane mimic challenging. To characterize protein-lipid contacts and bicelle membrane mimics, we examined protein-lipid cross-relaxation of integrin alpha IIb and beta 3(A711P) transmembrane helices in isotropic phospholipid bicelles (q = 0.5 and 0.7). Long-chain bicelle lipids dominated contacts with central helix segments, whereas both short- and long-chain lipids contacted the terminal turns of each helix in corroboration of the mixed bicelle model. The saturation transfer profiles from long chain lipids directly established helix midpoints in the lipid bilayer. Lipid headgroups and water molecules engaged the side chains of buried serine and threonine in competition with intrahelical hydrogen bonding, illustrating that polar side chains seek the most favorable electrostatic contacts.
C1 [Ulmer, Tobias S.] Univ Southern Calif, Keck Sch Med, Dept Biochem & Mol Med, 1501 San Pablo St, Los Angeles, CA 90033 USA.
Univ Southern Calif, Keck Sch Med, Zilkha Neurogenet Inst, 1501 San Pablo St, Los Angeles, CA 90033 USA.
[Schmidt, Thomas] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
RP Ulmer, TS (reprint author), Univ Southern Calif, Keck Sch Med, Dept Biochem & Mol Med, 1501 San Pablo St, Los Angeles, CA 90033 USA.
EM tulmer@usc.edu
FU American Heart Association [15GRNT23200010]
FX This work was supported by American Heart Association Grant
15GRNT23200010.
NR 33
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U1 4
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PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1948-7185
J9 J PHYS CHEM LETT
JI J. Phys. Chem. Lett.
PD NOV 3
PY 2016
VL 7
IS 21
BP 4420
EP 4426
DI 10.1021/acs.jpclett.6b02159
PG 7
WC Chemistry, Physical; Nanoscience & Nanotechnology; Materials Science,
Multidisciplinary; Physics, Atomic, Molecular & Chemical
SC Chemistry; Science & Technology - Other Topics; Materials Science;
Physics
GA EB2PT
UT WOS:000387205000029
PM 27776216
ER
PT J
AU Fowler, MG
Qin, M
Fiscus, SA
Currier, JS
Flynn, PM
Chipato, T
McIntyre, J
Gnanashanmugam, D
Siberry, GK
Coletti, AS
Taha, TE
Klingman, KL
Martinson, FE
Owor, M
Violari, A
Moodley, D
Theron, GB
Bhosale, R
Bobat, R
Chi, BH
Strehlau, R
Mlay, P
Loftis, AJ
Browning, R
Fenton, T
Purdue, L
Basar, M
Shapiro, DE
Mofenson, LM
AF Fowler, M. G.
Qin, M.
Fiscus, S. A.
Currier, J. S.
Flynn, P. M.
Chipato, T.
McIntyre, J.
Gnanashanmugam, D.
Siberry, G. K.
Coletti, A. S.
Taha, T. E.
Klingman, K. L.
Martinson, F. E.
Owor, M.
Violari, A.
Moodley, D.
Theron, G. B.
Bhosale, R.
Bobat, R.
Chi, B. H.
Strehlau, R.
Mlay, P.
Loftis, A. J.
Browning, R.
Fenton, T.
Purdue, L.
Basar, M.
Shapiro, D. E.
Mofenson, L. M.
CA IMPAACT 1077BF 1077FF PROMISE Stud
TI Benefits and Risks of Antiretroviral Therapy for Perinatal HIV
Prevention
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID TENOFOVIR DISOPROXIL FUMARATE; ADVERSE BIRTH OUTCOMES; INFECTED WOMEN;
PROGESTERONE LEVELS; LOPINAVIR EXPOSURE; PRETERM DELIVERY;
CHILD-MORTALITY; PREGNANCY; PROTEASE; LOPINAVIR/RITONAVIR
AB BACKGROUND
Randomized-trial data on the risks and benefits of antiretroviral therapy (ART) as compared with zidovudine and single-dose nevirapine to prevent transmission of the human immunodeficiency virus (HIV) in HIV-infected pregnant women with high CD4 counts are lacking.
METHODS
We randomly assigned HIV-infected women at 14 or more weeks of gestation with CD4 counts of at least 350 cells per cubic millimeter to zidovudine and single-dose nevirapine plus a 1-to-2-week postpartum "tail" of tenofovir and emtricitabine (zidovudine alone); zidovudine, lamivudine, and lopinavir-ritonavir (zidovudine-based ART); or tenofovir, emtricitabine, and lopinavir-ritonavir (tenofovir-based ART). The primary outcomes were HIV transmission at 1 week of age in the infant and maternal and infant safety.
RESULTS
The median CD4 count was 530 cells per cubic millimeter among 3490 primarily black African HIV-infected women enrolled at a median of 26 weeks of gestation (interquartile range, 21 to 30). The rate of transmission was significantly lower with ART than with zidovudine alone (0.5% in the combined ART groups vs. 1.8%; difference, -1.3 percentage points; repeated confidence interval, -2.1 to -0.4). However, the rate of maternal grade 2 to 4 adverse events was significantly higher with zidovudine-based ART than with zidovudine alone (21.1% vs. 17.3%, P = 0.008), and the rate of grade 2 to 4 abnormal blood chemical values was higher with tenofovir-based ART than with zidovudine alone (2.9% vs. 0.8%, P = 0.03). Adverse events did not differ significantly between the ART groups (P > 0.99). A birth weight of less than 2500 g was more frequent with zidovudine-based ART than with zidovudine alone (23.0% vs. 12.0%, P < 0.001) and was more frequent with tenofovir-based ART than with zidovudine alone (16.9% vs. 8.9%, P = 0.004); preterm delivery before 37 weeks was more frequent with zidovudine-based ART than with zidovudine alone (20.5% vs. 13.1%, P < 0.001). Tenofovir-based ART was associated with higher rates than zidovudine-based ART of very preterm delivery before 34 weeks (6.0% vs. 2.6%, P = 0.04) and early infant death (4.4% vs. 0.6%, P = 0.001), but there were no significant differences between tenofovir-based ART and zidovudine alone (P = 0.10 and P = 0.43). The rate of HIV-free survival was highest among infants whose mothers received zidovudine-based ART.
CONCLUSIONS
Antenatal ART resulted in significantly lower rates of early HIV transmission than zidovudine alone but a higher risk of adverse maternal and neonatal outcomes. (Funded by the National Institutes of Health; PROMISE ClinicalTrials.gov numbers, NCT01061151 and NCT01253538.)
C1 [Fowler, M. G.] Johns Hopkins Univ, Sch Med, Dept Pathol, 600 N Wolfe St,443 Carnegie, Baltimore, MD 21287 USA.
[Taha, T. E.] Johns Hopkins Univ, Dept Epidemiol, Bloomberg Sch Publ Hlth, Baltimore, MD USA.
[Gnanashanmugam, D.; Klingman, K. L.; Browning, R.; Purdue, L.] NIAID, Div Aids, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Siberry, G. K.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
[Qin, M.; Fenton, T.; Shapiro, D. E.] Harvard TH Chan Sch Publ Hlth, Ctr Biostat AIDS Res, Boston, MA USA.
[Fiscus, S. A.; Loftis, A. J.] Univ N Carolina, Sch Med, Retrovirol Core Lab, Chapel Hill, NC 27599 USA.
[Coletti, A. S.] FHI 360, Durham, NC USA.
[Currier, J. S.] Univ Calif Los Angeles, Ctr Clin AIDS Res & Educ, Los Angeles, CA USA.
[Flynn, P. M.] St Jude Childrens Res Hosp, 332 N Lauderdale St, Memphis, TN 38105 USA.
[Chipato, T.] Univ Zimbabwe, Coll Hlth Sci, Dept Obstet & Gynecol, Harare, Zimbabwe.
[McIntyre, J.] Univ Witwatersrand, Fac Hlth Sci, Anova Hlth Inst, Perinatal HIV Res, Johannesburg, South Africa.
[Violari, A.] Univ Witwatersrand, Fac Hlth Sci, Perinatal HIV Res Unit, Johannesburg, South Africa.
[Strehlau, R.] Empilweni Serv & Res Unit, Johannesburg, South Africa.
[McIntyre, J.] Univ Cape Town, Sch Publ Hlth & Family Med, ZA-7700 Rondebosch, South Africa.
[Theron, G. B.] Univ Stellenbosch, Dept Obstet & Gynaecol, Cape Town, South Africa.
[Moodley, D.] Univ KwaZulu Natal, Ctr AIDS Programme Res South Africa Umlazi Clin R, Nelson R Mandela Sch Med, Durban, South Africa.
[Bobat, R.] Univ KwaZulu Natal, Durban Paediat HIV, Nelson R Mandela Sch Med, Durban, South Africa.
[Martinson, F. E.] Univ North Carolina Project Kamuzu Cent Hosp Tidz, Lilongwe, Malawi.
[Owor, M.] Makerere Univ Johns Hopkins Univ Res Collaborat, Kampala, Uganda.
[Bhosale, R.] BJ Med Coll, Dept Obstet & Gynecol, Pune, Maharashtra, India.
[Chi, B. H.] Ctr Infect Dis Res Zambia, Lusaka, Zambia.
[Mlay, P.] Kilimanjaro Christian Med Center Duke Univ Collab, Moshi, Tanzania.
[Basar, M.] Frontier Sci & Technol Res Fdn Inc, Amherst, NY USA.
[Mofenson, L. M.] Elizabeth Glaser Pediat AIDS Fdn, Washington, DC USA.
RP Fowler, MG (reprint author), Johns Hopkins Univ, Sch Med, Dept Pathol, 600 N Wolfe St,443 Carnegie, Baltimore, MD 21287 USA.
EM mgfowler@mujhu.org
FU National Institute of Allergy and Infectious Diseases of the NIH
[UM1AI068632, UM1AI068616, UM1AI106716]; Eunice Kennedy Shriver National
Institute of Child Health and Human Development; National Institute of
Mental Health; Janssen; Gilead Sciences; ViiV Healthcare
FX Supported by the National Institute of Allergy and Infectious Diseases
of the NIH under award numbers UM1AI068632 (IMPAACT LOC), UM1AI068616
(IMPAACT SDMC), and UM1AI106716 (IMPAACT LC), with cofunding from the
Eunice Kennedy Shriver National Institute of Child Health and Human
Development and the National Institute of Mental Health.; Dr. Violari
reports receiving consulting fees from Janssen and grant support from
Gilead Sciences and ViiV Healthcare, all paid to her institution. No
other potential conflict of interest relevant to this article was
reported.
NR 27
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U2 5
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 NOV 3
PY 2016
VL 375
IS 18
BP 1726
EP 1737
DI 10.1056/NEJMoa1511691
PG 12
WC Medicine, General & Internal
SC General & Internal Medicine
GA EB0BB
UT WOS:000387007300006
PM 27806243
ER
PT J
AU Tripathi, A
Gottesman, S
AF Tripathi, Arti
Gottesman, Susan
TI CELL BIOLOGY Phosphate on, rubbish out
SO NATURE
LA English
DT News Item
ID QUALITY-CONTROL; PROTEIN; DESTRUCTION; MCSB
AB A previously unknown way in which cells mark proteins for destruction has been found in bacteria - phosphorylation of the amino acid arginine targets proteins for degradation by protease enzymes. SEE ARTICLE p.48
C1 [Tripathi, Arti; Gottesman, Susan] Natl Canc Inst, Mol Biol Lab, Bethesda, MD 20892 USA.
RP Gottesman, S (reprint author), Natl Canc Inst, Mol Biol Lab, Bethesda, MD 20892 USA.
EM gottesms@helix.nih.gov
NR 13
TC 0
Z9 0
U1 6
U2 6
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 3
PY 2016
VL 539
IS 7627
BP 38
EP 39
PG 2
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EA5OJ
UT WOS:000386670100022
PM 27808186
ER
PT J
AU Si, H
Lu, H
Yang, X
Mattox, A
Jang, M
Bian, Y
Sano, E
Viadiu, H
Yan, B
Yau, C
Ng, S
Lee, SK
Romano, RA
Davis, S
Walker, RL
Xiao, W
Sun, H
Wei, L
Sinha, S
Benz, CC
Stuart, JM
Meltzer, PS
Van Waes, C
Chen, Z
AF Si, H.
Lu, H.
Yang, X.
Mattox, A.
Jang, M.
Bian, Y.
Sano, E.
Viadiu, H.
Yan, B.
Yau, C.
Ng, S.
Lee, S. K.
Romano, R-A
Davis, S.
Walker, R. L.
Xiao, W.
Sun, H.
Wei, L.
Sinha, S.
Benz, C. C.
Stuart, J. M.
Meltzer, P. S.
Van Waes, C.
Chen, Z.
TI TNF-alpha modulates genome-wide redistribution of Delta Np63 alpha/TAp73
and NF-kappa B cREL interactive binding on TP53 and AP-1 motifs to
promote an oncogenic gene program in squamous cancer
SO ONCOGENE
LA English
DT Article
ID CELL CARCINOMA; C-JUN; TRANSCRIPTION FACTORS; TUMOR SUPPRESSION; SIGNAL
PATHWAYS; GROWTH-FACTOR; NECK-CANCER; P53 HOMOLOG; HUMAN HEAD; P63
AB The Cancer Genome Atlas (TCGA) network study of 12 cancer types (PanCancer 12) revealed frequent mutation of TP53, and amplification and expression of related TP63 isoform Delta Np63 in squamous cancers. Further, aberrant expression of inflammatory genes and TP53/p63/p73 targets were detected in the PanCancer 12 project, reminiscent of gene programs comodulated by cREL/Delta Np63/TAp73 transcription factors we uncovered in head and neck squamous cell carcinomas (HNSCCs). However, how inflammatory gene signatures and cREL/p63/p73 targets are comodulated genome wide is unclear. Here, we examined how the inflammatory factor tumor necrosis factor-alpha (TNF-alpha) broadly modulates redistribution of cREL with Delta Np63 alpha/TAp73 complexes and signatures genome wide in the HNSCC model UM-SCC46 using chromatin immunoprecipitation sequencing (ChIP-seq). TNF-alpha enhanced genome-wide co-occupancy of cREL with Delta Np63 alpha on TP53/p63 sites, while unexpectedly promoting redistribution of TAp73 from TP53 to activator protein-1 (AP-1) sites. cREL, Delta Np63 alpha and TAp73 binding and oligomerization on NF-kappa B-, TP53- or AP-1-specific sequences were independently validated by ChIP-qPCR (quantitative PCR), oligonucleotide-binding assays and analytical ultracentrifugation. Function of the binding activity was confirmed using TP53-, AP-1- and NF-kappa B-specific REs or p21, SERPINE1 and IL-6 promoter luciferase reporter activities. Concurrently, TNF-alpha regulated a broad gene network with cobinding activities for cREL, Delta Np63 alpha and TAp73 observed upon array profiling and reverse transcription-PCR. Overlapping target gene signatures were observed in squamous cancer subsets and in inflamed skin of transgenic mice overexpressing Delta Np63 alpha. Furthermore, multiple target genes identified in this study were linked to TP63 and TP73 activity and increased gene expression in large squamous cancer samples from PanCancer 12 TCGA by CircleMap. PARADIGM inferred pathway analysis revealed the network connection of TP63 and NF-kappa B complexes through an AP-1 hub, further supporting our findings. Thus, inflammatory cytokine TNF-a mediates genome-wide redistribution of the cREL/p63/p73, and AP-1 interactome, to diminish TAp73 tumor suppressor function and reciprocally activate NF-kappa B and AP-1 gene programs implicated in malignancy.
C1 [Si, H.; Lu, H.; Yang, X.; Mattox, A.; Jang, M.; Bian, Y.; Lee, S. K.; Van Waes, C.; Chen, Z.] NIDCD, Tumor Biol Sect, Head & Neck Surg Branch, NIH, Bethesda, MD USA.
[Lu, H.] Zhujiang Hosp Guangzhou, Orthopaed Ctr, Guangzhou, Guangdong, Peoples R China.
[Sano, E.] Univ Calif San Diego, Dept Chem & Biochem, San Diego, CA 92103 USA.
[Viadiu, H.] Univ Nacl Autonoma Mexico, Inst Quim, Ciudad Univ, Mexico City, DF, Mexico.
[Yan, B.] Univ Hong Kong, LKS Fac Med, Hong Kong, Hong Kong, Peoples R China.
[Yan, B.] Univ Hong Kong, LKS Fac Med, Sch Biomed Sci, Hong Kong, Hong Kong, Peoples R China.
[Yan, B.] Univ Hong Kong, Ctr Genome Sci, Hong Kong, Hong Kong, Peoples R China.
[Yau, C.; Benz, C. C.] Buck Inst Res Aging, Novato, CA USA.
[Ng, S.; Stuart, J. M.] Univ Calif Santa Cruz, Ctr Biomol Sci & Engn, Dept Biomol Engn, Santa Cruz, CA 95064 USA.
[Romano, R-A; Sinha, S.] SUNY Buffalo, Ctr Excellence Bioinformat & Life Sci, Dept Biochem, Buffalo, NY USA.
[Davis, S.; Walker, R. L.] NCI, Canc Genet Branch, Bethesda, MD 20892 USA.
[Xiao, W.] US FDA, Natl Ctr Toxicol Res, Div Bioinformat & Biostat, Jefferson, AK USA.
[Sun, H.] NIAMSD, Biodata Min & Discovery Sect, Bethesda, MD 20892 USA.
[Wei, L.] NEI, Clin Immunol Sect, NIH, Bethesda, MD 20892 USA.
[Wei, L.] Sun Yat Sen Univ, Zhongshan Ophthalm Ctr, State Key Lab Ophthalmol, Guangzhou, Guangdong, Peoples R China.
RP Van Waes, C (reprint author), NIDCD, NIH, Bldg 10-CRC,4-2732,10 Ctr Dr, Bethesda, MD 20892 USA.; Chen, Z (reprint author), NIDCD, Clin Genom Unit, Head & Neck Surg Branch, NIH, Bldg 10-5D55,10 Ctr Dr, Bethesda, MD 20892 USA.
EM vanwaesc@nidcd.nih.gov; chenz@nidcd.nih.gov
FU NIH [R01AR049238]; NCI [R01-CA180778, U24-CA143858]; Stand Up to Cancer;
Prostate Cancer Foundation; Movember Foundation; [ZIA-DC-000073];
[ZIA-DC-000074]
FX We thank Dr Fan Yang (NCI/NIH), Dr Kairong Cui (NHLBI/NIH), Dr Bingmei
Zhu (NIDDK/NIH), Jeffery Burnett (NIDCD/NIH), Jamie Coupar (NIDCD/NIH),
Guanmei Liang (Thomas Jefferson High School for Science and Technology,
Alexandria, VA, USA) and Eric Nicolson (Ithaca High School, Ithaca, New
York, NY, USA) for their technical assistance and suggestions. The
authors express appreciation to Drs James W Rocco and Leif W Ellisen
(Harvard University) for providing Delta Np63 and TAp63 expression
vectors, Dr Thomas Gilmore (Boston University) for cRel expression
plasmids, Professor Gerry Melino (University of Leicester) for TAp73
alpha expression plasmids, Dr J Silvio Gutkind (NIDCR/NIH) for IL-6
promoter reporter plasmids, Dr Gourisankar Ghosh (UCSD) for the cRel
expression plasmid, and Drs Michal Karin (University of California, San
Diego), Cheng-Ming Chiang (University of Texas, Southwestern) and Xuan
Liu (University of California, Riverside) for critique of and helpful
suggestions for the manuscript. HL, HS, XY, AM, MJ, YB, CVW and ZC are
supported by intramural projects ZIA-DC-000073, ZIA-DC-000074 and RAR
and SS are supported by a grant from NIH (R01AR049238). JMS acknowledges
support from NCI (R01-CA180778 and U24-CA143858), Stand Up to Cancer,
Prostate Cancer Foundation and the Movember Foundation.
NR 55
TC 0
Z9 0
U1 3
U2 3
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0950-9232
EI 1476-5594
J9 ONCOGENE
JI Oncogene
PD NOV 3
PY 2016
VL 35
IS 44
BP 5781
EP 5794
DI 10.1038/onc.2016.112
PG 14
WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
GA EA9XQ
UT WOS:000386998400009
PM 27132513
ER
PT J
AU Sekine, Y
Zyryanova, A
Crespillo-Casado, A
Amin-Wetzel, N
Harding, HP
Ron, D
AF Sekine, Yusuke
Zyryanova, Alisa
Crespillo-Casado, Ana
Amin-Wetzel, Niko
Harding, Heather P.
Ron, David
TI Paradoxical Sensitivity to an Integrated Stress Response Blocking
Mutation in Vanishing White Matter Cells
SO PLOS ONE
LA English
DT Article
ID ENDOPLASMIC-RETICULUM STRESS; UNFOLDED PROTEIN RESPONSE; TRANSLATION
INITIATION; DISEASE; EIF2B; PHOSPHORYLATION; EIF2-ALPHA; METABOLISM;
REPRESSION; DISORDERS
AB The eukaryotic translation initiation factor eIF2B promotes mRNA translation as a guanine nucleotide exchange factor (GEF) for translation initiation factor 2 (eIF2). Endoplasmic reticulum (ER) stress-mediated activation of the kinase PERK and the resultant phosphorylation of eIF2's alpha subunit (eIF2 alpha) attenuates eIF2B GEF activity thereby inducing an integrated stress response (ISR) that defends against protein misfolding in the ER. Mutations in all five subunits of human eIF2B cause an inherited leukoencephalopathy with vanishing white matter (VWM), but the role of the ISR in its pathogenesis remains unclear. Using CRISPR-Cas9 genome editing we introduced the most severe known VWM mutation, EIF2B4 A391D, into CHO cells. Compared to isogenic wildtype cells, GEF activity of cells with the VWM mutation was impaired and the mutant cells experienced modest enhancement of the ISR. However, despite their enhanced ISR, imposed by the intrinsic defect in eIF2B, disrupting the inhibitory effect of phosphorylated eIF2 alpha on GEF by a contravening EIF2S1/eIF2 alpha(S51A) mutation that functions upstream of eIF2B, selectively enfeebled both EIF2B4(A391D) and the related severe VWM EIF2B4(R483W) cells. The basis for paradoxical dependence of cells with the VWM mutations on an intact eIF2 alpha genotype remains unclear, as both translation rates and survival from stressors that normally activate the ISR were not reproducibly affected by the VWM mutations. Nonetheless, our findings support an additional layer of complexity in the development of VWM, beyond a hyperactive ISR.
C1 [Sekine, Yusuke; Zyryanova, Alisa; Crespillo-Casado, Ana; Amin-Wetzel, Niko; Harding, Heather P.; Ron, David] Univ Cambridge, Cambridge Inst Med Res, Cambridge, England.
[Sekine, Yusuke] NHLBI, Ctr Mol Med, NIH, Bldg 10, Bethesda, MD 20892 USA.
RP Sekine, Y; Ron, D (reprint author), Univ Cambridge, Cambridge Inst Med Res, Cambridge, England.; Sekine, Y (reprint author), NHLBI, Ctr Mol Med, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM yusuke.sekine@nih.gov; dr360@medschl.cam.ac.uk
OI Sekine, Yusuke/0000-0003-0345-1416; Ron, David/0000-0002-3014-5636
FU Wellcome Trust [200848/Z/16/Z, 100140]; European Commission (EU FP7
Beta-Bat) [277713]; Medical Research Council
FX Supported by grants from the Wellcome Trust (Wellcome 200848/Z/16/Z) and
the European Commission (EU FP7 Beta-Bat No: 277713) and, a Wellcome
Trust Strategic Award for core facilities to the Cambridge Institute for
Medical Research (Wellcome 100140). YS is a Japanese Society for the
Promotion of Science Postdoctoral Fellow for Research Abroad. NAW is a
Medical Research Council supported PhD student. DR is a Wellcome Trust
Principal Research Fellow. Wellcome Trust URL;
http://www.wellcome.ac.uk, JSPS URL; https://www.jsps.go.jp, MRC URL;
http://www.mrc.ac.uk. The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 28
TC 1
Z9 1
U1 1
U2 1
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD NOV 3
PY 2016
VL 11
IS 11
AR e0166278
DI 10.1371/journal.pone.0166278
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EA8SX
UT WOS:000386910000107
PM 27812215
ER
PT J
AU Ader, NR
AF Ader, Nicholas R.
TI Seeking an In Vivo Neuronal Context for the PINK1/Parkin Pathway
SO JOURNAL OF NEUROSCIENCE
LA English
DT Editorial Material
ID MITOCHONDRIAL QUALITY-CONTROL; PARKINSONS-DISEASE; MAMMALIAN-CELLS;
REQUIRES PINK1; MITOPHAGY; DEGRADATION; MUTATIONS; AUTOPHAGY;
DROSOPHILA; STRESS
C1 [Ader, Nicholas R.] Med Res Council Lab Mol Biol, Div Cell Biol, Cambridge CB2 0QH, England.
[Ader, Nicholas R.] Natl Inst Neurol Disorders & Stroke, Biochem Sect, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA.
RP Ader, NR (reprint author), MRC Lab Mol Biol, Francis Crick Ave,Cambridge Biomed Campus, Cambridge CB2 0QH, England.
EM nader@mrc-lmb.cam.ac.uk
FU Medical Research Council [MC_UP_1201/8]
NR 31
TC 0
Z9 0
U1 1
U2 1
PU SOC NEUROSCIENCE
PI WASHINGTON
PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA
SN 0270-6474
J9 J NEUROSCI
JI J. Neurosci.
PD NOV 2
PY 2016
VL 36
IS 44
BP 11165
EP 11167
DI 10.1523/JNEUROSCI.2525-16.2016
PG 3
WC Neurosciences
SC Neurosciences & Neurology
GA EG4YN
UT WOS:000391050100005
PM 27807159
ER
PT J
AU Suzuki, TW
Kunimatsu, J
Tanaka, M
AF Suzuki, Tomoki W.
Kunimatsu, Jun
Tanaka, Masaki
TI Correlation between Pupil Size and Subjective Passage of Time in
Non-Human Primates
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
DE eye movements; monkeys; pupil diameter; self-timing; temporal processing
ID RAT PREFRONTAL CORTEX; LOCUS-COERULEUS; NEURONAL-ACTIVITY; NORADRENERGIC
MODULATION; ELECTRICAL-STIMULATION; CINGULATE CORTEX; DECISION-MAKING;
ADAPTIVE GAIN; MOTOR CORTEX; NEURAL BASIS
AB Our daily experience of time is strongly influenced by internal states, such as arousal, attention, and mood. However, the underlying neuronal mechanism remains largely unknown. To investigate this, we recorded pupil diameter, which is closely linked to internal factors and neuromodulatory signaling, in monkeys performing the oculomotor version of the time production paradigm. In the self-timed saccade task, animals were required to make a memory-guided saccade during a predetermined time interval following a visual cue. We found that pupil diameter was negatively correlated with trial-by-trial latency of self-timed saccades. Because no significant correlation was found for visually guided saccades, correlation of self-timed saccades could not be explained solely by the facilitation of saccade execution. As the reward amount was manipulated, pupil diameter and saccade latency altered in opposite directions and the magnitudes of modulation correlated strongly across sessions, further supporting the close link between pupil diameter and the subjective passage of time. When the animals were trained to produce two different intervals depending on the instruction, the pupil size again correlated with the trial-by-trial variation of saccade latency in each condition; however, pupil diameter differed significantly for saccades with similar latencies generated under different conditions. Our results indicate that internal brain states indexed by pupil diameter, which parallel noradrenergic neuronal activity (Aston-Jones and Cohen, 2005), may bias trial-by-trial variation in the subjective passage of time.
C1 [Suzuki, Tomoki W.; Kunimatsu, Jun; Tanaka, Masaki] Hokkaido Univ, Dept Physiol, Sch Med, North 15,West 7, Sapporo, Hokkaido 0608638, Japan.
[Kunimatsu, Jun] NEI, Sensorimotor Res Lab, NIH, Bldg 10, Bethesda, MD 20892 USA.
RP Tanaka, M (reprint author), Hokkaido Univ, Dept Physiol, Sch Med, North 15,West 7, Sapporo, Hokkaido 0608638, Japan.
EM masaki@med.hokudai.ac.jp
RI Tanaka, Masaki/D-9199-2011
FU Ministry of Education, Culture, Sports, Science and Technology of Japan;
Ministry of Health, Labour and Welfare of Japan; Takeda Science
Foundation
FX This work was supported by the Ministry of Education, Culture, Sports,
Science and Technology of Japan, the Ministry of Health, Labour and
Welfare of Japan, and the Takeda Science Foundation. Animals were
provided by the National Bio-Resource Project. We thank A. Narumi and H.
Arime for participating in the early part of the experiments; T. Mori
and A. Hironaka for assistance with animal care and surgery; M. Suzuki
for administrative help; M. Takei and Y. Hirata for manufacturing
equipment; K. Matsuda (Human Informatics Research Institute, AIST) for
providing software for the eye tracking system; and all laboratory
members for comments and discussions.
NR 62
TC 1
Z9 1
U1 2
U2 2
PU SOC NEUROSCIENCE
PI WASHINGTON
PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA
SN 0270-6474
J9 J NEUROSCI
JI J. Neurosci.
PD NOV 2
PY 2016
VL 36
IS 44
BP 11331
EP 11337
DI 10.1523/JNEUROSCI.2533-16.2016
PG 7
WC Neurosciences
SC Neurosciences & Neurology
GA EG4YN
UT WOS:000391050100019
PM 27807173
ER
PT J
AU Lambrughi, M
De Gioia, L
Gervasio, FL
Lindorff-Larsen, K
Nussinov, R
Urani, C
Bruschi, M
Papaleo, E
AF Lambrughi, Matteo
De Gioia, Luca
Gervasio, Francesco Luigi
Lindorff-Larsen, Kresten
Nussinov, Ruth
Urani, Chiara
Bruschi, Maurizio
Papaleo, Elena
TI DNA-binding protects p53 from interactions with cofactors involved in
transcription-independent functions
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID MOLECULAR-DYNAMICS SIMULATIONS; TUMOR-SUPPRESSOR P53; FULL-LENGTH P53;
FREE-ENERGY LANDSCAPE; CRYSTAL-STRUCTURE; CORE DOMAIN; INDUCED FIT;
COMMUNICATION PATHWAYS; FORCE-FIELD; MUTANT P53
AB Binding-induced conformational changes of a protein at regions distant from the binding site may play crucial roles in protein function and regulation. The p53 tumour suppressor is an example of such an allosterically regulated protein. Little is known, however, about how DNA binding can affect distal sites for transcription factors. Furthermore, the molecular details of how a local perturbation is transmitted through a protein structure are generally elusive and occur on timescales hard to explore by simulations. Thus, we employed state-of-the-art enhanced sampling atomistic simulations to unveil DNA-induced effects on p53 structure and dynamics that modulate the recruitment of cofactors and the impact of phosphorylation at Ser215. We show that DNA interaction promotes a conformational change in a region 3 nm away from the DNA binding site. Specifically, binding to DNA increases the population of an occluded minor state at this distal site by more than 4-fold, whereas phosphorylation traps the protein in its major state. In the minor conformation, the interface of p53 that binds biological partners related to p53 transcription-independent functions is not accessible. Significantly, our study reveals a mechanism of DNA-mediated protection of p53 from interactions with partners involved in the p53 transcription-independent signalling. This also suggests that conformational dynamics is tightly related to p53 signalling.
C1 [Lambrughi, Matteo; Papaleo, Elena] Unit Stat Bioinformat & Registry, Computat Biol Lab, Strandboulevarden 49, DK-2100 Copenhagen, Denmark.
[Lambrughi, Matteo; Lindorff-Larsen, Kresten; Papaleo, Elena] Univ Copenhagen, Dept Biol, Struct Biol & NMR Lab, Copenhagen, Denmark.
[De Gioia, Luca] Univ Milano Bicocca, Dept Biotechnol & Biosci, Piazza Sci 2, I-20126 Milan, Italy.
[Gervasio, Francesco Luigi] UCL, Dept Chem, London WC1H 0AJ, England.
[Gervasio, Francesco Luigi] UCL, Inst Struct & Mol Biol, London WC1H 0AJ, England.
[Nussinov, Ruth] NCI, Canc & Inflammat Program, Leidos Biomed Res Inc, Frederick Natl Lab, Frederick, MD 21702 USA.
[Nussinov, Ruth] Tel Aviv Univ, Sackler Sch Med, Dept Human Mol Genet & Biochem, IL-69978 Tel Aviv, Israel.
[Urani, Chiara; Bruschi, Maurizio] Univ Milano Bicocca, Dept Earth & Environm Sci, Piazza Sci 1, I-20126 Milan, Italy.
RP Papaleo, E (reprint author), Unit Stat Bioinformat & Registry, Computat Biol Lab, Strandboulevarden 49, DK-2100 Copenhagen, Denmark.; Papaleo, E (reprint author), Univ Copenhagen, Dept Biol, Struct Biol & NMR Lab, Copenhagen, Denmark.
EM elenap@cancer.dk
RI Lindorff-Larsen, Kresten/K-6469-2014
OI Lindorff-Larsen, Kresten/0000-0002-4750-6039
FU PRACE-DECI project DyNet; ISCRA-CINECA HPC [HP10BLFPW4, HP10C8LO8N];
HECBioSim allocation on Archer; Danish Cancer Society Research Center
(DCRC); Novo Nordisk Foundation; EPSRC [EP/M013898/1]; National Cancer
Institute, National Institutes of Health [HHSN261200800001E]; Intramural
Research Program of the NIH, National Cancer Institute, Center for
Cancer Research
FX PRACE-DECI project DyNet, the ISCRA-CINECA HPC Grants [HP10BLFPW4 and
HP10C8LO8N]; HECBioSim allocation on Archer; Danish Cancer Society
Research Center (DCRC) [to E.P.]; Hallas-Moller stipend from the Novo
Nordisk Foundation [K.L.-L. and E.P.]; EPSRC [EP/M013898/1 to F.L.G. in
part]; National Cancer Institute, National Institutes of Health
[HHSN261200800001E]; Intramural Research Program of the NIH, National
Cancer Institute, Center for Cancer Research [in part]. Funding for open
access charge: PRACE-DECI project DyNet, the ISCRA-CINECA HPC Grants
[HP10BLFPW4 and HP10C8LO8N]; HECBioSim allocation on Archer; Danish
Cancer Society Research Center (DCRC) [to E.P.]; Hallas-Moller stipend
from the Novo Nordisk Foundation [K.L.-L. and E.P.]; EPSRC [EP/M013898/1
to F.L.G. in part]; National Cancer Institute, National Institutes of
Health [HHSN261200800001E]; Intramural Research Program of the NIH,
National Cancer Institute, Center for Cancer Research [in part].
NR 98
TC 1
Z9 1
U1 17
U2 17
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
EI 1362-4962
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD NOV 2
PY 2016
VL 44
IS 19
BP 9096
EP 9109
DI 10.1093/nar/gkw770
PG 14
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA EC3HK
UT WOS:000388016900011
PM 27604871
ER
PT J
AU Kent, T
Rusanov, TD
Hoang, TM
Velema, WA
Krueger, AT
Copeland, WC
Kool, ET
Pomerantz, RT
AF Kent, Tatiana
Rusanov, Timur D.
Hoang, Trung M.
Velema, Willem A.
Krueger, Andrew T.
Copeland, William C.
Kool, Eric T.
Pomerantz, Richard T.
TI DNA polymerase theta specializes in incorporating synthetic
expanded-size (xDNA) nucleotides
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID BASE-PAIRS; ERRONEOUS INCORPORATION; CANCER PATIENTS; GENETIC SYSTEM;
BREAST-CANCER; UP-REGULATION; POLQ; REPLICATION; FIDELITY; BYPASS
AB DNA polymerase theta (Pol theta) is a unique A-family polymerase that is essential for alternative end-joining (alt-EJ) of double-strand breaks (DSBs) and performs translesion synthesis. Because Pol theta is highly expressed in cancer cells, confers resistance to ionizing radiation and chemotherapy agents, and promotes the survival of homologous recombination (HR) deficient cells, it represents a promising new cancer drug target. As a result, identifying substrates that are selective for this enzyme is a priority. Here, we demonstrate that Pol theta efficiently and selectively incorporates into DNA large benzo-expanded nucleotide analogs (dxAMP, dxGMP, dxTMP, dxAMP) which exhibit canonical base-pairing and enhanced base stacking. In contrast, functionally related Y-family translesion polymerases exhibit a severely reduced ability to incorporate dxNMPs, and all other human polymerases tested from the X, B and A families fail to incorporate them under the same conditions as Pol theta. We further find that Pol theta is inhibited after multiple dxGMP incorporation events, and that Pol theta efficiency for dxGMP incorporation approaches that of native dGMP. These data demonstrate a unique function for Pol theta in incorporating synthetic large-sized nucleotides and suggest the future possibility of the use of dxG nucleoside or related prodrug analogs as selective inhibitors of Pol theta activity.
C1 [Kent, Tatiana; Rusanov, Timur D.; Hoang, Trung M.; Pomerantz, Richard T.] Temple Univ, Lewis Katz Sch Med, Dept Med Genet & Mol Biochem, Fels Inst Canc Res, Philadelphia, PA 19140 USA.
[Velema, Willem A.; Krueger, Andrew T.; Kool, Eric T.] Stanford Univ, Dept Chem, Stanford, CA 94305 USA.
[Copeland, William C.] NIEHS, Lab Mol Genet, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.
RP Pomerantz, RT (reprint author), Temple Univ, Lewis Katz Sch Med, Dept Med Genet & Mol Biochem, Fels Inst Canc Res, Philadelphia, PA 19140 USA.
EM richard.pomerantz@temple.edu
FU National Institutes of Health [4R00CA160648-03, 1R21CA209281-01]; Army
Research Office [W911NF-13-1-0181]; Netherlands Organisation for
Scientific Research; EMBO [ALTF 934-2014]; NIH
FX National Institutes of Health [4R00CA160648-03 and 1R21CA209281-01
awarded to R.T.P.]. Army Research Office [W911NF-13-1-0181 to E.T.K.];
The Netherlands Organisation for Scientific Research and EMBO [ALTF
934-2014 to W.A.V.]. Funding for open access charge: NIH.
NR 43
TC 1
Z9 1
U1 6
U2 6
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
EI 1362-4962
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD NOV 2
PY 2016
VL 44
IS 19
BP 9381
EP 9392
DI 10.1093/nar/gkw721
PG 12
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA EC3HK
UT WOS:000388016900033
PM 27591252
ER
PT J
AU Greely, HT
Ramos, KM
Grady, C
AF Greely, Henry T.
Ramos, Khara M.
Grady, Christine
TI Neuroethics in the Age of Brain Projects
SO NEURON
LA English
DT Editorial Material
AB Neuroscience advances have brought important ethical questions. The recent launch of two large brain projects, the United States BRAIN Initiative and the European Union Human Brain Project, should accelerate progress in understanding the brain. This article examines neuroethics in those two projects, as well as its exploration by other efforts.
C1 [Greely, Henry T.] Stanford Univ, Ctr Law & Biosci, Stanford, CA 94305 USA.
[Greely, Henry T.] Stanford Univ, Stanford Program Neurosci & Soc, Stanford, CA 94305 USA.
[Ramos, Khara M.] NINDS, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
[Grady, Christine] NIH, Dept Bioeth, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA.
RP Greely, HT (reprint author), Stanford Univ, Ctr Law & Biosci, Stanford, CA 94305 USA.; Greely, HT (reprint author), Stanford Univ, Stanford Program Neurosci & Soc, Stanford, CA 94305 USA.
EM hgreely@stanford.edu
NR 10
TC 1
Z9 1
U1 6
U2 6
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0896-6273
EI 1097-4199
J9 NEURON
JI Neuron
PD NOV 2
PY 2016
VL 92
IS 3
BP 637
EP 641
DI 10.1016/j.neuron.2016.10.048
PG 5
WC Neurosciences
SC Neurosciences & Neurology
GA EA6TU
UT WOS:000386762700018
PM 27810008
ER
PT J
AU Sam-Agudu, NA
Paintsil, E
Aliyu, MH
Kwara, A
Ogunsola, F
Afrane, YA
Onoka, C
Awandare, GA
Amponsah, G
Cornelius, LJ
Mendy, G
Sturke, R
Ghansah, A
Siberry, GK
Ezeanolue, EE
AF Sam-Agudu, Nadia A.
Paintsil, Elijah
Aliyu, Muktar H.
Kwara, Awewura
Ogunsola, Folasade
Afrane, Yaw A.
Onoka, Chima
Awandare, Gordon A.
Amponsah, Gladys
Cornelius, Llewellyn J.
Mendy, Gabou
Sturke, Rachel
Ghansah, Anita
Siberry, George K.
Ezeanolue, Echezona E.
TI Building Sustainable Local Capacity for Global Health Research in West
Africa
SO ANNALS OF GLOBAL HEALTH
LA English
DT Article
DE western Africa; capacity-building; financial support; global health;
research
ID DEVELOPING-COUNTRIES; CLINICAL-TRIALS; EPIDEMIOLOGY; EDCTP; SOUTH;
BIOSTATISTICS; PARTNERSHIP; EXCELLENCE; PROGRAM
AB BACKGROUND Global health research in resource-limited countries has been largely sponsored and led by foreign institutions. Thus, these countries' training capacity and productivity in global health research is limited. Local participation at all levels of global health knowledge generation promotes equitable access to evidence-based solutions. Additionally, leadership inclusive of competent local professionals promotes best outcomes for local contextualization and implementation of successful global health solutions. Among the sub-Saharan African regions, West Africa in particular lags in research infrastructure, productivity, and impact in global health research.
OBJECTIVE In this paper, experts discuss strategies for scaling up West Africa's participation in global health evidence generation using examples from Ghana and Nigeria.
METHODS We conducted an online and professional network search to identify grants awarded for global health research and research education in Ghana and Nigeria. Principal investigators, global health educators, and representatives of funding institutions were invited to add their knowledge and expertise with regard to strengthening research capacity in West Africa.
FINDINGS While there has been some progress in obtaining foreign funding, foreign institutions still dominate local research. Local research funding opportunities in the 2 countries were found to be insufficient, disjointed, poorly sustained, and inadequately publicized, indicating weak infrastructure. As a result, research training programs produce graduates who ultimately fail to launch independent investigator careers because of lack of mentoring and poor infrastructural support.
CONCLUSIONS Research funding and training opportunities in Ghana and Nigeria remain inadequate.
RECOMMENDATIONS We recommend systems-level changes in mentoring, collaboration, and funding to drive the global health research agenda in these countries. Additionally, research training programs should be evaluated not only by numbers of individuals graduated but also by numbers of independent investigators and grants funded. Through equitable collaborations, infrastructure, and mentoring, West Africa can match the rest of Africa in impactful global health research.
C1 [Sam-Agudu, Nadia A.] Univ Maryland, Sch Med, Inst Human Virol, Baltimore, MD 21201 USA.
[Sam-Agudu, Nadia A.] Univ Maryland, Sch Med, Dept Pediat, Baltimore, MD 21201 USA.
[Sam-Agudu, Nadia A.] Int Res Ctr Excellence, Inst Human Virol Nigeria, Abuja, Nigeria.
[Sam-Agudu, Nadia A.] Univ Cape Coast, Sch Med Sci, Dept Paediat, Cape Coast, Ghana.
[Paintsil, Elijah] Yale Sch Med, Dept Pediat, New Haven, CT USA.
[Aliyu, Muktar H.] Vanderbilt Inst Global Hlth, Nashville, TN USA.
[Aliyu, Muktar H.] Vanderbilt Univ, Med Ctr, Dept Prevent Med, Nashville, TN USA.
[Kwara, Awewura] Univ Florida, Coll Med, Dept Med, Gainesville, FL USA.
[Ogunsola, Folasade] Univ Lagos, Dept Med Microbiol & Parasitol, Coll Med, Lagos, Nigeria.
[Afrane, Yaw A.] Univ Ghana, Coll Hlth Sci, Dept Med Microbiol, Legon, Ghana.
[Onoka, Chima] Univ Nigeria, Dept Community Med, Enugu, Nigeria.
[Awandare, Gordon A.] Univ Ghana, West African Ctr Cell Biol Infect Pathogens, Dept Biochem Cell & Mol Biol, Legon, Ghana.
[Amponsah, Gladys] Ridge Reg Hosp, Sch Anaesthesia, Accra, Ghana.
[Cornelius, Llewellyn J.] Univ Georgia, Sch Social Work, Athens, GA USA.
[Mendy, Gabou] Healing Healthcare, New Orleans, LA USA.
[Sturke, Rachel] NIH, Div Int Policy Planning & Evaluat, Fogarty Int Ctr, Bldg 10, Bethesda, MD 20892 USA.
[Sturke, Rachel] NIH, Ctr Global Hlth Studies, Fogarty Int Ctr, Bldg 10, Bethesda, MD 20892 USA.
[Ghansah, Anita] Noguchi Mem Inst Med Res, Legon, Ghana.
[Ezeanolue, Echezona E.] Univ Nevada, Sch Community Hlth Sci, Las Vegas, NV 89154 USA.
[Ezeanolue, Echezona E.] Univ Nigeria, Coll Med, Enugu, Nigeria.
RP Sam-Agudu, NA (reprint author), Univ Maryland, Sch Med, Inst Human Virol, Baltimore, MD 21201 USA.; Sam-Agudu, NA (reprint author), Univ Maryland, Sch Med, Dept Pediat, Baltimore, MD 21201 USA.; Sam-Agudu, NA (reprint author), Int Res Ctr Excellence, Inst Human Virol Nigeria, Abuja, Nigeria.; Sam-Agudu, NA (reprint author), Univ Cape Coast, Sch Med Sci, Dept Paediat, Cape Coast, Ghana.
EM nsam-agudu@ihv.umaryland.edu
OI Awandare, Gordon/0000-0002-8793-3641
NR 60
TC 0
Z9 0
U1 2
U2 2
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 2214-9996
J9 ANN GLOB HEALTH
JI Ann. Glob. Health
PD NOV-DEC
PY 2016
VL 82
IS 6
BP 1010
EP 1025
DI 10.1016/j.aogh.2016.10.011
PG 16
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA EO4VA
UT WOS:000396691200008
PM 28314488
ER
PT J
AU Hoge, CW
Ivany, CG
Schoenbaum, M
AF Hoge, Charles W.
Ivany, Christopher G.
Schoenbaum, Michael
TI Death by suicide in US military during the Afghanistan and Iraq wars
SO LANCET PSYCHIATRY
LA English
DT Editorial Material
ID SERVICE MEMBERS; MENTAL-HEALTH; RISK; VETERANS; ARMY
C1 [Hoge, Charles W.] Walter Reed Army Inst Res, Ctr Psychiat & Neurosci, Silver Spring, MD 20910 USA.
[Ivany, Christopher G.] Off Army Surgeon Gen, Falls Church, VA USA.
[Schoenbaum, Michael] NIMH, Div Serv & Intervent Res, Bethesda, MD 20892 USA.
RP Hoge, CW (reprint author), Walter Reed Army Inst Res, Ctr Psychiat & Neurosci, Silver Spring, MD 20910 USA.
EM charles.w.hoge.civ@mail.mil
NR 12
TC 0
Z9 0
U1 1
U2 1
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 2215-0374
J9 LANCET PSYCHIAT
JI Lancet Psychiatry
PD NOV
PY 2016
VL 3
IS 11
BP 1001
EP 1003
DI 10.1016/S2215-0366(16)30305-4
PG 4
WC Psychiatry
SC Psychiatry
GA EN9UL
UT WOS:000396345000008
PM 27697515
ER
PT J
AU Thrift, AP
Anderson, LA
Murray, LJ
Cook, MB
Shaheen, NJ
Rubenstein, JH
El-Serag, HB
Vaughan, TL
Schneider, JL
Whiteman, DC
Corley, DA
AF Thrift, Aaron P.
Anderson, Lesley A.
Murray, Liam J.
Cook, Michael B.
Shaheen, Nicholas J.
Rubenstein, Joel H.
El-Serag, Hashem B.
Vaughan, Thomas L.
Schneider, Jennifer L.
Whiteman, David C.
Corley, Douglas A.
TI Nonsteroidal Anti-Inflammatory Drug Use is Not Associated With Reduced
Risk of Barrett's Esophagus
SO AMERICAN JOURNAL OF GASTROENTEROLOGY
LA English
DT Article
ID ADENOCARCINOMA SEQUENCE; CYCLOOXYGENASE-2; INHIBITION; ASPIRIN; CANCER;
METAANALYSIS; EXPRESSION; MORTALITY; TRENDS
AB OBJECTIVES: Regular use of nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with a reduced risk of esophageal adenocarcinoma. Epidemiological studies examining the association between NSAID use and the risk of the precursor lesion, Barrett's esophagus, have been inconclusive.
METHODS: We analyzed pooled individual-level participant data from six case-control studies of Barrett's esophagus in the Barrett's and Esophageal Adenocarcinoma Consortium (BEACON). We compared medication use from 1,474 patients with Barrett's esophagus separately with two control groups: 2,256 population-based controls and 2,018 gastroesophageal reflux disease (GERD) controls. Study-specific odds ratio (OR) and 95% confidence intervals (CI) were estimated using multivariable logistic regression models and were combined using a random-effects meta-analytic model.
RESULTS: Regular (at least once weekly) use of any NSAIDs was not associated with the risk of Barrett's esophagus (vs. population-based controls, adjusted OR=1.00, 95% CI=0.76-1.32, I-2=61%; vs. GERD controls, adjusted OR=0.99, 95% CI=0.82-1.19, I-2=19%). Similar null findings were observed among individuals who took aspirin or non-aspirin NSAIDs. We also found no association with highest levels of frequency (at least daily use) and duration (>= 5 years) of NSAID use. There was evidence of moderate between-study heterogeneity; however, associations with NSAID use remained non-significant in "leave-one-out" sensitivity analyses.
CONCLUSIONS: Use of NSAIDs was not associated with the risk of Barrett's esophagus. The previously reported inverse association between NSAID use and esophageal adenocarcinoma may be through reducing the risk of neoplastic progression in patients with Barrett's esophagus.
C1 [Thrift, Aaron P.; Cook, Michael B.; Shaheen, Nicholas J.; Schneider, Jennifer L.] Baylor Coll Med, Sect Gastroenterol & Hepatol, Dept Med, Houston, TX 77030 USA.
[Thrift, Aaron P.; El-Serag, Hashem B.; Schneider, Jennifer L.] Baylor Coll Med, Dan L Duncan Comprehens Canc Ctr, Houston, TX 77030 USA.
[Murray, Liam J.; Vaughan, Thomas L.; Whiteman, David C.] Queens Univ Belfast, Ctr Publ Hlth, Belfast, Antrim, North Ireland.
[Murray, Liam J.; El-Serag, Hashem B.; Schneider, Jennifer L.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Murray, Liam J.; El-Serag, Hashem B.; Whiteman, David C.] Univ N Carolina, Sch Med, Div Gastroenterol & Hepatol, Chapel Hill, NC USA.
[Cook, Michael B.; Vaughan, Thomas L.; Schneider, Jennifer L.] Ann Arbor Vet Affairs Med Ctr, Ctr Clin Management Res, Ann Arbor, MI USA.
[Cook, Michael B.; El-Serag, Hashem B.; Whiteman, David C.] Univ Michigan, Div Gastroenterol, Dept Internal Med, Barretts Esophagus Program, Ann Arbor, MI USA.
[Murray, Liam J.; El-Serag, Hashem B.; Whiteman, David C.] Houston VA HSR Ctr Innovat Qual, Dept Med, Michael DeBakey VA Med Ctr, Effectiveness & Safety, Houston, TX USA.
[Cook, Michael B.; Vaughan, Thomas L.; Whiteman, David C.] Fred Hutchinson Canc Res Ctr, Program Epidemiol, Seattle, WA USA.
[Murray, Liam J.; El-Serag, Hashem B.; Schneider, Jennifer L.] Calif & San Francisco Med Ctr, Kaiser Permanente Div Res, Oakland, CA USA.
[Murray, Liam J.; El-Serag, Hashem B.; Corley, Douglas A.] QIMR Berghofer Med Res Inst, Brisbane, Qld, Australia.
RP Thrift, AP (reprint author), Baylor Coll Med, Dan L Duncan Comprehens Canc Ctr, Houston, TX 77030 USA.
EM aaron.thrift@bcm.edu
OI Anderson, Lesley/0000-0002-1000-3649; Whiteman,
David/0000-0003-2563-9559
FU National Institutes of Health [RO1 DK63616, 1R21DK077742, K23DK59311,
R03 DK75842, K23DK079291, R01 CA116845, K24-04-107]; Intramural Program
of the National Institutes of Health; Ireland-Northern Ireland
cooperation research project grant - the Northern Ireland Research and
Development Office; Health Research Board, Ireland (FINBAR)
[RES/1699/01N/S]; Study of Digestive Health [NCI RO1 CA 001833]; Study
of Reflux Disease [NCI R01 CA72866]; Established Investigator Award in
Cancer Prevention and Control [K05 CA124911]; US Department of Veterans
Affairs CSRD Merit [I01-CX000899]
FX This work was supported by the National Institutes of Health RO1 DK63616
(D.A.C.); 1R21DK077742 (N.J.S. and D.A.C.); K23DK59311 (N.J.S.); R03
DK75842 (N.J.S.); K23DK079291 (J.H.R.); R01 CA116845 (H.B.E.-S.);
K24-04-107 (H.B.E.-S.); the Intramural Program of the National
Institutes of Health (M.B.C.); an Ireland-Northern Ireland cooperation
research project grant sponsored by the Northern Ireland Research and
Development Office and the Health Research Board, Ireland (FINBAR;
L.J.M.: RES/1699/01N/S); the Study of Digestive Health, NCI RO1 CA
001833 (D.C.W.); the Study of Reflux Disease, NCI R01 CA72866 (T.L.V.),
the Established Investigator Award in Cancer Prevention and Control, K05
CA124911 (T.L.V.), and the US Department of Veterans Affairs CSRD Merit
I01-CX000899 (J.H.R.).
NR 28
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PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0002-9270
EI 1572-0241
J9 AM J GASTROENTEROL
JI Am. J. Gastroenterol.
PD NOV
PY 2016
VL 111
IS 11
BP 1528
EP 1535
DI 10.1038/ajg.2016.348
PG 8
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA EK6PT
UT WOS:000394047300014
PM 27575711
ER
PT J
AU Harada, M
Kamijo, Y
Nakajima, T
Hashimoto, K
Yamada, Y
Shimojo, H
Gonzalez, FJ
Aoyama, T
AF Harada, Makoto
Kamijo, Yuji
Nakajima, Takero
Hashimoto, Koji
Yamada, Yosuke
Shimojo, Hisashi
Gonzalez, Frank J.
Aoyama, Toshifumi
TI Peroxisome proliferator-activated receptor alpha-dependent
renoprotection of murine kidney by irbesartan
SO CLINICAL SCIENCE
LA English
DT Article
DE angiotensin II type 1 receptor blocker; fatty acid metabolism;
irbesartan (Irbe); peroxisome proliferator-activated receptor alpha
(PPAR alpha)
ID PPAR-ALPHA; TUBULOINTERSTITIAL DAMAGE; GENE-EXPRESSION;
DIABETIC-NEPHROPATHY; HYPERTENSIVE-RATS; PROXIMAL TUBULES; OXIDATIVE
STRESS; GAMMA AGONIST; RENAL-DISEASE; FATTY-ACIDS
AB Activation of renal peroxisome proliferator-activated receptor alpha (PPAR alpha) is renoprotective, but there is no safe PPARa activator for patients with chronic kidney disease (CKD). Studies have reported that irbesartan (Irbe), an angiotensin II receptor blocker (ARB) widely prescribed for CKD, activates hepatic PPAR alpha. However, Irbe's renal PPAR alpha-activating effects and the role of PPAR alpha signalling in the renoprotective effects of Irbe are unknown. Herein, these aspects were investigated in healthy kidneys of wild-type (WT) and Ppara-null (KO) mice and in the murine protein-overload nephropathy (PON) model respectively. The results were compared with those of losartan (Los), another ARB that does not activate PPAR alpha. PPAR alpha and its target gene expression were significantly increased only in the kidneys of Irbe-treated WT mice and not in KO or Los-treated mice, suggesting that the renal PPAR alpha-activating effect was Irbe-specific. Irbe-treated-PON-WT mice exhibited decreased urine protein excretion, tubular injury, oxidative stress (OS), and pro-inflammatory and apoptosis-stimulating responses, and they exhibited maintenance of fatty acid metabolism. Furthermore, the expression of PPAR alpha and that of its target mRNAs encoding proteins involved in OS, pro-inflammatory responses, apoptosis and fatty acid metabolism was maintained upon Irbe treatment. These renoprotective effects of Irbe were reversed by the PPAR alpha antagonist MK886 and were not detected in Irbe-treated-PON-KO mice. These results suggest that Irbe activates renal PPAR alpha and that the resultant increased PPAR alpha signalling mediates its renoprotective effects.
C1 [Harada, Makoto; Kamijo, Yuji; Hashimoto, Koji; Yamada, Yosuke] Shinshu Univ, Dept Nephrol, Sch Med, 3-1-1 Asahi, Matsumoto, Nagano 3908621, Japan.
[Harada, Makoto; Kamijo, Yuji; Nakajima, Takero; Yamada, Yosuke; Aoyama, Toshifumi] Shinshu Univ, Grad Sch Med, Inst Pathogenesis & Dis Prevent, Dept Metab Regulat, 3-1-1 Asahi, Matsumoto, Nagano 3908621, Japan.
[Shimojo, Hisashi] Shinshu Univ, Sch Med, Dept Pathol, 3-1-1 Asahi, Matsumoto, Nagano 3908621, Japan.
[Gonzalez, Frank J.] NCI, Lab Metab, Bethesda, MD 20892 USA.
RP Kamijo, Y (reprint author), Shinshu Univ, Dept Nephrol, Sch Med, 3-1-1 Asahi, Matsumoto, Nagano 3908621, Japan.; Kamijo, Y (reprint author), Shinshu Univ, Grad Sch Med, Inst Pathogenesis & Dis Prevent, Dept Metab Regulat, 3-1-1 Asahi, Matsumoto, Nagano 3908621, Japan.
EM yujibeat@shinshu-u.ac.jp
FU Sumitomo Dainippon Pharma Co.; [25460329]
FX This work was supported by the Sumitomo Dainippon Pharma Co. and
Grants-in-Aid for Scientific Research (KAKENHI) in Japan [grant number
25460329].
NR 45
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U1 0
U2 0
PU PORTLAND PRESS LTD
PI LONDON
PA CHARLES DARWIN HOUSE, 12 ROGER STREET, LONDON WC1N 2JU, ENGLAND
SN 0143-5221
EI 1470-8736
J9 CLIN SCI
JI Clin. Sci.
PD NOV 1
PY 2016
VL 130
IS 21
BP 1969
EP 1981
DI 10.1042/CS20160343
PG 13
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA EK2PR
UT WOS:000393769700011
PM 27496805
ER
PT J
AU Schuebel, K
Gitik, M
Domschke, K
Goldman, D
AF Schuebel, Kornel
Gitik, Miri
Domschke, Katharina
Goldman, David
TI Making Sense of Epigenetics
SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY
LA English
DT Review
DE epigenetics; DNA methylation; chromatin; neuropsychiatric disorders
ID HISTONE DEACETYLASE INHIBITORS; SUBSTANCE USE DISORDERS;
LONG-TERM-MEMORY; DNA METHYLATION; SYNAPTIC PLASTICITY; GENE-EXPRESSION;
BIPOLAR DISORDER; MONOZYGOTIC TWINS; MONOAMINE-OXIDASE;
BRAIN-DEVELOPMENT
AB The gene-environment interactions that underlie development and progression of psychiatric illness are poorly understood. Despite a century of progress, genetic approaches have failed to identify new treatment modalities, perhaps because of the heterogeneity of the disorders and lack of understanding of mechanisms. Recent exploration into epigenetic mechanisms in health and disease has uncovered changes in DNA methylation and chromatin structure that may contribute to psychiatric disorders. Epigenetic changes suggest a variety of new therapeutic options due to their reversible chemistry. However, distinguishing causal links between epigenetic changes and disease from changes consequent to life experience has remained problematic. Here we define epigenetics and explore aspects of epigenetics relevant to causes and mechanisms of psychiatric disease, and speculate on future directions.
C1 [Schuebel, Kornel; Gitik, Miri; Goldman, David] NIAAA, Neurogenet Lab, NIH, 5625 Fishers Lane,Rm 3s-32, Rockville, MD 20852 USA.
[Schuebel, Kornel; Gitik, Miri; Goldman, David] NIAAA, Off Clin Director, NIH, Rockville, MD 20852 USA.
[Domschke, Katharina] Univ Wurzburg, Dept Psychiat Psychosomat & Psychotherapy, Wurzburg, Germany.
RP Goldman, D (reprint author), NIAAA, Neurogenet Lab, NIH, 5625 Fishers Lane,Rm 3s-32, Rockville, MD 20852 USA.
EM david.goldman@nih.gov
FU National Institutes of Health, National Institute for Alcohol Abuse and
Alcoholism; German Research Foundation (DFG) [SFB-TRR-58]; German
Ministry of Research and Education (BMBF) [01EE1402A]
FX The present work was supported by intramural funding from the National
Institutes of Health, National Institute for Alcohol Abuse and
Alcoholism, the German Research Foundation (DFG, SFB-TRR-58, C02 to
K.D.), and the German Ministry of Research and Education (BMBF,
01EE1402A, PROTECT-AD, P5 to K.D.). We apologize to those whose work has
not been cited due to space constraints.
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PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1461-1457
EI 1469-5111
J9 INT J NEUROPSYCHOPH
JI Int. J. Neuropsychopharmacol.
PD NOV
PY 2016
VL 19
IS 11
DI 10.1093/ijnp/pyw058
PG 10
WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA EK4QO
UT WOS:000393912100001
ER
PT J
AU Allen, NE
Travis, RC
Appleby, PN
Albanes, D
Barnett, MJ
Black, A
Bueno-De-Mesquita, HB
Deschasaux, M
Galan, P
Goodman, GE
Goodman, PJ
Gunter, MJ
Heliovaara, M
Helzlsouer, KJ
Henderson, BE
Hercberg, S
Knekt, P
Kolonel, LN
Lasheras, C
Linseisen, J
Metter, EJ
Neuhouser, ML
Olsen, A
Pala, V
Platz, EA
Rissanen, H
Reid, ME
Schenk, JM
Stampfer, MJ
Stattin, P
Tangen, CM
Touvier, M
Trichopoulou, A
van den Brandt, PA
Key, TJ
AF Allen, Naomi E.
Travis, Ruth C.
Appleby, Paul N.
Albanes, Demetrius
Barnett, Matt J.
Black, Amanda
Bueno-de-Mesquita, H. Bas
Deschasaux, Melanie
Galan, Pilar
Goodman, Gary E.
Goodman, Phyllis J.
Gunter, Marc J.
Heliovaara, Markku
Helzlsouer, Kathy J.
Henderson, Brian E.
Hercberg, Serge
Knekt, Paul
Kolonel, Laurence N.
Lasheras, Christina
Linseisen, Jakob
Metter, E. Jeffrey
Neuhouser, Marian L.
Olsen, Anja
Pala, Valeria
Platz, Elizabeth A.
Rissanen, Harri
Reid, Mary E.
Schenk, Jeannette M.
Stampfer, Meir J.
Stattin, Par
Tangen, Catherine M.
Touvier, Mathilde
Trichopoulou, Antonia
van den Brandt, Piet A.
Key, Timothy J.
CA Endogenous Hormones Nutr Biomakers
TI Selenium and Prostate Cancer: Analysis of Individual Participant Data
From Fifteen Prospective Studies
SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Article
ID SERUM SELENIUM; SUBSEQUENT RISK; SELENOPROTEIN P; TRIAL; ASSOCIATION;
TOENAILS; MEN; SUPPLEMENTATION; PREVENTION; POLYMORPHISMS
AB Background: Some observational studies suggest that a higher selenium status is associated with a lower risk of prostate cancer but have been generally too small to provide precise estimates of associations, particularly by disease stage and grade.
Methods: Collaborating investigators from 15 prospective studies provided individual-participant records (from predominantly men of white European ancestry) on blood or toenail selenium concentrations and prostate cancer risk. Odds ratios of prostate cancer by selenium concentration were estimated using multivariable-adjusted conditional logistic regression. All statistical tests were two-sided.
Results: Blood selenium was not associated with the risk of total prostate cancer (multivariable-adjusted odds ratio [OR] per 80 percentile increase = 1.01, 95% confidence interval [CI] = 0.83 to 1.23, based on 4527 case patients and 6021 control subjects). However, there was heterogeneity by disease aggressiveness (ie, advanced stage and/or prostate cancer death, P-heterogeneity = .01), with high blood selenium associated with a lower risk of aggressive disease (OR = 0.43, 95% CI = 0.21 to 0.87) but not with nonaggressive disease. Nail selenium was inversely associated with total prostate cancer (OR = 0.29, 95% CI = 0.22 to 0.40, P-trend <.001, based on 1970 case patients and 2086 control subjects), including both nonaggressive (OR = 0.33, 95% CI = 0.22 to 0.50) and aggressive disease (OR = 0.18, 95% CI = 0.11 to 0.31, P-heterogeneity =.08).
Conclusions: Nail, but not blood, selenium concentration is inversely associated with risk of total prostate cancer, possibly because nails are a more reliable marker of long-termselenium exposure. Both blood and nail selenium concentrations are associated with a reduced risk of aggressive disease, which warrants further investigation.
C1 [Allen, Naomi E.] Univ Oxford, Nuffield Dept Populat Hlth, Clin Trial Serv Unit, Richard Doll Bldg, Oxford OX3 7LF, England.
[Allen, Naomi E.] Univ Oxford, Nuffield Dept Populat Hlth, Epidemiol Studies Unit, Richard Doll Bldg, Oxford OX3 7LF, England.
[Travis, Ruth C.; Appleby, Paul N.; Key, Timothy J.] Univ Oxford, Nuffield Dept Populat Hlth, Canc Epidemiol Unit, Oxford, England.
[Albanes, Demetrius; Black, Amanda] US Natl Canc Inst, Div Canc Epidemiol & Genet, Bethesda, MD USA.
[Barnett, Matt J.; Goodman, Gary E.; Neuhouser, Marian L.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA.
[Goodman, Phyllis J.; Tangen, Catherine M.] Fred Hutchinson Canc Res Ctr, SWOG, Seattle, WA 98104 USA.
[Schenk, Jeannette M.] Fred Hutchinson Canc Res Ctr, Canc Prevent Program, Seattle, WA 98104 USA.
[Schenk, Jeannette M.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
[Tangen, Catherine M.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
[Bueno-de-Mesquita, H. Bas] Natl Inst Publ Hlth & Environm RIVM, Dept Determinants Chron Dis, Bilthoven, Netherlands.
[Bueno-de-Mesquita, H. Bas] Univ Med Ctr, Dept Gastroenterol & Hepatol, Utrecht, Netherlands.
[Bueno-de-Mesquita, H. Bas; Gunter, Marc J.] Imperial Coll London, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England.
[Bueno-de-Mesquita, H. Bas] Univ Malaya, Fac Med, Dept Social & Prevent Med, Kuala Lumpur, Malaysia.
[Deschasaux, Melanie; Galan, Pilar; Hercberg, Serge; Touvier, Mathilde] Univ Paris 07, Univ Paris 05,Nutr Epidemiol Res Team, Univ Paris 13,Inserm U1153,Inra U1125,Cnam, Sorbonne Paris Cite Epidemiol & Biostat, Bobigny, France.
[Heliovaara, Markku; Knekt, Paul; Rissanen, Harri] Natl Inst Hlth & Welf, Helsinki, Finland.
[Helzlsouer, Kathy J.] Mercy Med Ctr, Prevent & Res Ctr, Baltimore, MD USA.
[Henderson, Brian E.] Univ Southern Calif, Keck Sch Med, Norris Comprehens Canc Ctr, Dept Prevent Med, Los Angeles, CA 90033 USA.
[Kolonel, Laurence N.] Univ Hawaii, Ctr Canc, Honolulu, HI 96822 USA.
[Lasheras, Christina] Univ Oviedo, Fac Med, Dept Funct Biol, Asturias, Spain.
[Linseisen, Jakob] Helmholtz Zentrum Munchen, Inst Epidemiol 2, Neuherberg, Germany.
[Linseisen, Jakob] German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany.
[Metter, E. Jeffrey] Univ Tennessee, Ctr Hlth Sci, Dept Neurol, Intramural Res Programm,Natl Inst Aging, Memphis, TN 38163 USA.
[Olsen, Anja] Danish Canc Soc Res Ctr, Copenhagen, Denmark.
[Pala, Valeria] IRCCS, Ist Nazl Tumori, Epidemiol & Prevent Unit, I-20133 Milan, Italy.
[Platz, Elizabeth A.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
[Reid, Mary E.] Roswell Pk Canc Inst, New York, NY USA.
[Stampfer, Meir J.] Harvard Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.
[Stampfer, Meir J.] Harvard Med Sch, Brigham & Womens Hosp, Channing Div Network Med, Boston, MA USA.
[Stattin, Par] Umea Univ, Dept Surg & Perioperat Sci, Urol & Androl, Umea, Sweden.
[Trichopoulou, Antonia] Hellen Hlth Fdn, Athens, Greece.
[van den Brandt, Piet A.] Maastricht Univ, GROW Sch Oncol & Dev Biol, Dept Epidemiol, NL-6200 MD Maastricht, Netherlands.
RP Allen, NE (reprint author), Univ Oxford, Nuffield Dept Populat Hlth, Clin Trial Serv Unit, Richard Doll Bldg, Oxford OX3 7LF, England.; Allen, NE (reprint author), Univ Oxford, Nuffield Dept Populat Hlth, Epidemiol Studies Unit, Richard Doll Bldg, Oxford OX3 7LF, England.
EM naomi.allen@ndph.ox.ac.uk
FU Cancer Research UK [C570/A11691, C8221/A19170]; National Institute on
Aging Intramural Research Program, Prostate Spore Grant [CA58236]; US
Department of Health and Human Services; National Institutes of Health
[U01 CA63673, P01 CA 33619, R37 CA 54281, RO1 CA49764, CA37429, CA42182,
CA58684, CA57374, CA94028, CA55075]; Clinical Nutrition Research Unit
[P30 DK35816]; Department of Defense [DAMD1-94-J-4265]; Europe Against
Cancer Programme of the European Commission; German Cancer Aid; German
Cancer Research Center; German Federal Ministry of Education and
Research; Danish Cancer Society; Health Research Fund of the Spanish
Ministry of Health; Centros de Investigacion Biomedica en Red
Epidemiologia y Salud Publica, Barcelona, Spain; Medical Research
Council, UK; Stroke Association (UK); British Heart Foundation;
Department of Health (UK); Food Standards Agency (UK); Greek Ministry of
Education; Greek Ministry of Health and Social Solidarity; Hellenic
Health Foundation; Italian Association for Research on Cancer; Italian
National Research Council; Dutch Ministry of Public Health, Welfare and
Sports; Dutch Ministry of Health; Dutch Prevention Funds; LK Research
Funds; Dutch Zorg Onderzoek Nederland; World Cancer Research Fund;
Swedish Cancer Society; Swedish Scientific Council; Regional Government
of Skane, Sweden; German Federal Ministry of Education and Research [FK
0313846A]; Deutsche Krebshilfe [10-1793 Scholl]; Cancer Society of
Finland; National Heart, Lung, and Blood Institute [HL35464]; US
National Cancer Institute; Dutch Cancer Society [UM 2009-4556];
Intramural Research Program; French Ministry of Health/Direction
Generale de la Sante
FX This work was supported by Cancer Research UK (grant numbers
C570/A11691, C8221/A19170). We thank the men who participated in the
collaborating studies, the research staff, the collaborating
laboratories, and the funding agencies in each of the studies. BLSA was
supported by the National Institute on Aging Intramural Research
Program, Prostate Spore Grant (CA58236). CARET was supported by the US
Department of Health and Human Services and the National Institutes of
Health (U01 CA63673), Clinical Nutrition Research Unit (P30 DK35816).
Campaign against Cancer and Stroke was supported by the US National
Cancer Institute, the National Institutes of Health (CA94028), and the
Department of Defense (DAMD1-94-J-4265). European Investigation into
Cancer and Nutrition was supported by Cancer Research UK; Europe Against
Cancer Programme of the European Commission; German Cancer Aid; German
Cancer Research Center; German Federal Ministry of Education and
Research; Danish Cancer Society; Health Research Fund of the Spanish
Ministry of Health; Centros de Investigacion Biomedica en Red
Epidemiologia y Salud Publica, Barcelona, Spain; the participating
regional governments and institutions of Spain; Medical Research
Council, UK; the Stroke Association (UK); British Heart Foundation;
Department of Health (UK); Food Standards Agency (UK); Greek Ministry of
Education; Greek Ministry of Health and Social Solidarity; Hellenic
Health Foundation; Italian Association for Research on Cancer; Italian
National Research Council; Dutch Ministry of Public Health, Welfare and
Sports; Dutch Ministry of Health; Dutch Prevention Funds; LK Research
Funds; Dutch Zorg Onderzoek Nederland; World Cancer Research Fund;
Swedish Cancer Society; Swedish Scientific Council; and Regional
Government of Skane, Sweden. EPIC-Heidelberg was supported by the German
Federal Ministry of Education and Research (FK 0313846A), Deutsche
Krebshilfe (10-1793 Scholl). Finnish Mobile Clinic Health Examination
was supported by the Cancer Society of Finland. Health Professionals
Follow-up Study was supported by the US National Cancer Institute, the
National Institutes of Health (CA55075), and the National Heart, Lung,
and Blood Institute (HL35464). Multiethnic Cohort was supported by the
US National Cancer Institute and the National Institutes of Health (P01
CA 33619, R37 CA 54281). Nutritional Prevention of Cancer Trial was
supported by the US National Cancer Institute and the National
Institutes of Health (RO1 CA49764). Netherlands Cohort Study was
supported by the Dutch Cancer Society (UM 2009-4556). Prostate Cancer
Prevention Trial and Selenium and Vitamin E Cancer Prevention Trial
(SouthWest Oncology Group) were supported by the US National Cancer
Institute and the National Institutes of Health (CA37429). Physicians'
Health Study was supported by the US National Cancer Institute and the
National Institutes of Health (CA42182, CA58684, CA57374). Prostate,
Lung, Colorectal and Ovarian Cancer Screening Trial was supported by the
US National Cancer Institute, the National Institutes of Health (PLCO
Cancer Screening Trial), and the Intramural Research Program.
SUpplementation en Vitamines et Mineraux Anti-oXydants Trial was
supported by the French Ministry of Health/Direction Generale de la
Sante.
NR 49
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U1 2
U2 2
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0027-8874
EI 1460-2105
J9 JNCI-J NATL CANCER I
JI JNCI-J. Natl. Cancer Inst.
PD NOV
PY 2016
VL 108
IS 11
AR djw153
DI 10.1093/jnci/djw153
PG 8
WC Oncology
SC Oncology
GA EK4LD
UT WOS:000393897300012
ER
PT J
AU Miyake, K
Suzuki, A
Morita, C
Goto, M
Newman, DJ
O'Keefe, BR
Morris-Natschke, SL
Lee, KH
Nakagawa-Goto, K
AF Miyake, Katsunori
Suzuki, Airi
Morita, Chihiro
Goto, Masuo
Newman, David J.
O'Keefe, Barry R.
Morris-Natschke, Susan L.
Lee, Kuo-Hsiung
Nakagawa-Goto, Kyoko
TI Acetophenone Monomers from Acronychia trifoliolata
SO JOURNAL OF NATURAL PRODUCTS
LA English
DT Article
ID PEDUNCULATA; DERIVATIVES
AB Seven new [acronyculatins I-0 (1-7)] and four known acetophenone monomers were isolated from a CH3OH/CH2C12 (1:1) extract (N089419) of Acronychia trifoliolata provided by the U.S. National Cancer Institute (NCI, Frederick, MD, USA). Their structures were characterized by using various NMR and HEMS techniques. Among the known compounds, the structure of acronyculatin B (8) was revised. Some of the isolated compounds were evaluated for antiproliferative activity against human cancer cell lines. While most of the tested compounds were not cytotoxic, acronyculatins I (1) and J (2) showed moderate antiproliferative activity.
C1 [Miyake, Katsunori; Suzuki, Airi; Morita, Chihiro; Nakagawa-Goto, Kyoko] Kanazawa Univ, Coll Med Pharmaceut & Hlth Sci, Sch Pharmaceut Sci, Kanazawa, Ishikawa 9201192, Japan.
[Goto, Masuo; Morris-Natschke, Susan L.; Lee, Kuo-Hsiung; Nakagawa-Goto, Kyoko] Univ North Carolina Chapel Hill, UNC Eshelman Sch Pharm, Nat Prod Res Labs, Chapel Hill, NC 27599 USA.
[Newman, David J.] NIH Special Volunteer, Wayne, PA 19087 USA.
[O'Keefe, Barry R.] NCI Frederick, NCI, Nat Prod Branch, Dev Therapeut Program,Div Canc Treatment & Diag, Frederick, MD 21702 USA.
[Lee, Kuo-Hsiung] China Med Univ & Hosp, Chinese Med Res & Dev Ctr, 2 Yuh Der Rd, Taichung 40447, Taiwan.
RP Nakagawa-Goto, K (reprint author), Kanazawa Univ, Coll Med Pharmaceut & Hlth Sci, Sch Pharmaceut Sci, Kanazawa, Ishikawa 9201192, Japan.; Nakagawa-Goto, K (reprint author), Univ North Carolina Chapel Hill, UNC Eshelman Sch Pharm, Nat Prod Res Labs, Chapel Hill, NC 27599 USA.
EM kngoto@p.kanazawa-u.ac.jp
FU Ministry of Education, Culture, Sports, Science and Technology (MEXT
KAKENHI, Japan) [25293024]; NIH [CA177584]; National Cancer Institute,
awarded
FX This study was supported by a Grant-in-Aid from the Ministry of
Education, Culture, Sports, Science and Technology (MEXT KAKENHI,
Japan), awarded to K.N.G. (Grant Number 25293024). This work was also
supported by NIH Grant CA177584 from the National Cancer Institute,
awarded to K.H.L. We also thank the Biological Testing Branch, DTP,
DCTD, NCI, for performing the NCI 60-cell cytotoxicity assay and the
Natural Products Support Group, Leidos Biomedical Inc., for plant
extraction.
NR 15
TC 1
Z9 1
U1 2
U2 2
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0163-3864
EI 1520-6025
J9 J NAT PROD
JI J. Nat. Prod.
PD NOV
PY 2016
VL 79
IS 11
BP 2883
EP 2889
DI 10.1021/acs.jnatprod.6b00645
PG 7
WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy
SC Plant Sciences; Pharmacology & Pharmacy
GA EL1VX
UT WOS:000394410600014
PM 27797192
ER
PT J
AU Hibbett, D
Abarenkov, K
Koljalg, U
Opik, M
Chai, B
Cole, J
Wang, Q
Crous, P
Robert, V
Helgason, T
Herr, JR
Kirk, P
Lueschow, S
O'Donnell, K
Nilsson, RH
Oono, R
Schoch, C
Smyth, C
Walker, DM
Porras-Alfaro, A
Taylor, JW
Geiser, DM
AF Hibbett, David
Abarenkov, Kessy
Koljalg, Urmas
Opik, Maarja
Chai, Benli
Cole, James
Wang, Qiong
Crous, Pedro
Robert, Vincent
Helgason, Thorunn
Herr, Joshua R.
Kirk, Paul
Lueschow, Shiloh
O'Donnell, Kerry
Nilsson, R. Henrik
Oono, Ryoko
Schoch, Conrad
Smyth, Christopher
Walker, Donald M.
Porras-Alfaro, Andrea
Taylor, John W.
Geiser, David M.
TI Sequence-based classification and identification of Fungi
SO MYCOLOGIA
LA English
DT Review
DE biodiversity informatics; metagenomics; molecular ecology; nomenclature;
systematics; taxonomy
ID INTERNAL TRANSCRIBED SPACER; RIBOSOMAL DATABASE PROJECT; ARBUSCULAR
MYCORRHIZAL FUNGI; OPERATIONAL TAXONOMIC UNITS; SPECIES LIVING TREE; RNA
GENE DATABASE; AD-HOC-COMMITTEE; LARGE-SUBUNIT;
MOLECULAR-IDENTIFICATION; ENVIRONMENTAL SEQUENCES
AB Fungal taxonomy and ecology have been revolutionized by the application of molecular methods and both have increasing connections to genomics and functional biology. However, data streams from traditional specimen- and culture-based systematics are not yet fully integrated with those from metagenomic and metatranscriptomic studies, which limits understanding of the taxonomic diversity and metabolic properties of fungal communities. This article reviews current resources, needs, and opportunities for sequence-based classification and identification (SBCI) in fungi as well as related efforts in prokaryotes. To realize the full potential of fungal SBCI it will be necessary to make advances in multiple areas. Improvements in sequencing methods, including long-read and single-cell technologies, will empower fungal molecular ecologists to look beyond ITS and current shotgun metagenomics approaches. Data quality and accessibility will be enhanced by attention to data and metadata standards and rigorous enforcement of policies for deposition of data and workflows. Taxonomic communities will need to develop best practices for molecular characterization in their focal clades, while also contributing to globally useful datasets including ITS. Changes to nomenclatural rules are needed to enable valid publication of sequence-based taxon descriptions. Finally, cultural shifts are necessary to promote adoption of SBCI and to accord professional credit to individuals who contribute to community resources.
C1 [Hibbett, David] Clark Univ, Dept Biol, Worcester, MA 01610 USA.
[Abarenkov, Kessy; Koljalg, Urmas; Opik, Maarja] Univ Tartu, Inst Ecol & Earth Sci, 40 Lai St, EE-51005 Tartu, Estonia.
[Chai, Benli; Cole, James; Wang, Qiong] Michigan State Univ, Dept Plant Soil & Microbial Sci, Plant & Soil Sci Bldg,1066 Bogue St,Room 540, E Lansing, MI 48824 USA.
[Crous, Pedro; Robert, Vincent] Cent Bur Schimmelcultures Fungal Biodivers Ctr CB, NL-3508 AD Utrecht, Netherlands.
[Helgason, Thorunn] Univ York, Dept Biol, York YO10 5DD, N Yorkshire, England.
[Herr, Joshua R.] Univ Nebraska, Dept Plant Pathol, Lincoln, NE 68503 USA.
[Herr, Joshua R.] Univ Nebraska, Ctr Plant Sci Innovat, Lincoln, NE 68503 USA.
[Kirk, Paul] Royal Bot Gardens, Biodivers Informat & Spatial Anal, Richmond TW9 3AF, Surrey, England.
[Lueschow, Shiloh; O'Donnell, Kerry] NCAUR ARS USDA, 1815 N Univ St, Peoria, IL 61604 USA.
[Nilsson, R. Henrik] Univ Gothenburg, Dept Biol & Environm Sci, S-40530 Gothenburg, Sweden.
[Oono, Ryoko] Univ Calif Santa Barbara, Dept Ecol Evolut & Marine Biol, Santa Barbara, CA 93106 USA.
[Schoch, Conrad] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA.
[Smyth, Christopher; Geiser, David M.] Penn State Univ, Dept Plant Pathol & Environm Microbiol, 121 Buckhout Lab, University Pk, PA 16802 USA.
[Walker, Donald M.] Tennessee Technol Univ, Dept Biol, 1100 N Dixie Ave, Cookeville, TN 38505 USA.
[Porras-Alfaro, Andrea] Western Illinois Univ, Dept Biol Sci, Waggoner Hall 372,1 Univ Circle, Macomb, IL 61455 USA.
[Taylor, John W.] Univ Calif Berkeley, Dept Plant & Microbial Biol, 111 Koshland Hall, Berkeley, CA 94720 USA.
RP Hibbett, D (reprint author), Clark Univ, Dept Biol, Worcester, MA 01610 USA.
EM dhibbett@clarku.edu
FU US National Science Foundation [DEB 1424740]; Intramural Research
Program of the National Institutes of Health, National Library of
Medicine; Estonian Research Council [IUT20-28]; European Regional
Development Fund (Centre of Excellence EcolChange); NSF [DEB-1208719]
FX Preparation of this article was initiated in a 2 d workshop on SBCI in
Fungi that was held at the Kellogg Center of Michigan State University,
East Lansing, Michigan, 12-13 Jun 2014 (Herr et al. 2015), which was
supported by US National Science Foundation award No. DEB 1424740 to DG,
AP-A, DSH, and JWT. A related symposium on "Sequence-based
identification in Fungi" was held on 11 Jun 2014 at the annual meeting
of the Mycological Society of America, and a Special Interest Group
session on "Classifying, naming and communicating sequence based
species" took place at the International Mycological Congress, 5 Aug
2014, Bangkok, Thailand. The authors thank Sam Kovaka, who performed the
query of GenBank for species names (FIG. 2, SUPPLEMENTARY INFORMATION),
P. Brandon Matheny, and two anonymous reviewers for helpful comments.
Mention of trade names or commercial products in this publication is
solely for the purpose of providing specific information and does not
imply recommendation or endorsement by the Victorian government or the
US Department of Agriculture. USDA is an equal opportunity provider and
employer. CLS acknowledges support from the Intramural Research Program
of the National Institutes of Health, National Library of Medicine. MO
acknowledges support from the Estonian Research Council (grant No.
IUT20-28) and European Regional Development Fund (Centre of Excellence
EcolChange). DSH acknowledges support of NSF award No. DEB-1208719.
NR 142
TC 0
Z9 0
U1 10
U2 10
PU ALLEN PRESS INC
PI LAWRENCE
PA 810 E 10TH ST, LAWRENCE, KS 66044 USA
SN 0027-5514
EI 1557-2536
J9 MYCOLOGIA
JI Mycologia
PD NOV-DEC
PY 2016
VL 108
IS 6
BP 1049
EP 1068
DI 10.3852/16-130
PG 20
WC Mycology
SC Mycology
GA EJ5PA
UT WOS:000393269000001
ER
PT J
AU Brosse, A
Korobeinikova, A
Gottesman, S
Guillier, M
AF Brosse, Anais
Korobeinikova, Anna
Gottesman, Susan
Guillier, Maude
TI Unexpected properties of sRNA promoters allow feedback control via
regulation of a two-component system
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID ESCHERICHIA-COLI K-12; HISTIDINE KINASE ENVZ; GENE-EXPRESSION;
OUTER-MEMBRANE; TRANSCRIPTION FACTORS; SIGNAL-TRANSDUCTION; NEGATIVE
REGULATION; BIOFILM FORMATION; FEEDFORWARD LOOP; DNA RECOGNITION
AB Two-component systems (TCS) and small regulatory RNAs (sRNAs) are both widespread regulators of gene expression in bacteria. TCS are in most cases transcriptional regulators. A large class of sRNAs act as post-transcriptional regulators of gene expression that modulate the translation and/or stability of target-mRNAs. Many connections have been recently unraveled between these two types of regulators, resulting in mixed regulatory circuits with poorly characterized properties. This study focuses on the negative feedback circuit that exists between the EnvZ-OmpR TCS and the OmrA/B sRNAs. We have shown that OmpR directly activates transcription from the omrA and omrB promoters, allowing production of OmrA/B sRNAs that target multiple mRNAs, including the ompR-envZ mRNA. This control of ompR-envZ by the Omr sRNAs does not affect the amount of phosphorylated OmpR, i.e. the presumably active form of the regulator. Accordingly, expression of robust OmpR targets, such as the ompC or ompF porin genes, is not affected by OmrA/B. However, we find that several OmpR targets, including OmrA/B themselves, are sensitive to changing total OmpR levels. As a result, OmrA/B limit their own synthesis. These findings unravel an additional layer of control in the expression of some OmpR targets and suggest the existence of differential regulation within the OmpR regulon.
C1 [Brosse, Anais; Korobeinikova, Anna; Guillier, Maude] Univ Paris Diderot, CNRS, UMR8261, Sorbonne Paris Cite,Inst Biol Physicochim, F-75005 Paris, France.
[Gottesman, Susan] NCI, Mol Biol Lab, NIH, Bldg 37, Bethesda, MD 20892 USA.
RP Guillier, M (reprint author), Univ Paris Diderot, CNRS, UMR8261, Sorbonne Paris Cite,Inst Biol Physicochim, F-75005 Paris, France.
EM maude.guillier@ibpc.fr
FU CNRS; ANR [ANR-2010-JCJC-130801, ANR-14-CE10-0004-01]; 'Initiative
d'Excellence' program from the French State ['DYNAMO']
[ANR-11-LABX-0011]; Intramural Research Program of the NIH, National
Cancer Institute, Center for Cancer Research
FX CNRS, ANR [ANR-2010-JCJC-130801 and ANR-14-CE10-0004-01 to M.G.];
'Initiative d'Excellence' program from the French State ['DYNAMO',
ANR-11-LABX-0011]; Intramural Research Program of the NIH, National
Cancer Institute, Center for Cancer Research. Funding for open access
charge: ANR (french national research agency) [ANR-14-CE10-0004-01].
NR 70
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
EI 1362-4962
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD NOV
PY 2016
VL 44
IS 20
BP 9650
EP 9666
DI 10.1093/nar/gkw642
PG 17
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA EK3HR
UT WOS:000393817800018
PM 27439713
ER
PT J
AU Kim, SH
Trinh, AT
Larsen, MC
Mastrocola, AS
Jefcoate, CR
Bushel, PR
Tibbetts, RS
AF Kim, Sang Hwa
Trinh, Anthony T.
Larsen, Michele Campaigne
Mastrocola, Adam S.
Jefcoate, Colin R.
Bushel, Pierre R.
Tibbetts, Randal S.
TI Tunable regulation of CREB DNA binding activity couples genotoxic stress
response and metabolism
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID EXPRESSION MICROARRAY DATA; GENOME-WIDE ANALYSIS; NUCLEAR FACTOR CREB;
TRANSCRIPTION FACTOR; GENE-EXPRESSION; MULTISITE PHOSPHORYLATION;
ATAXIA-TELANGIECTASIA; UNSTRUCTURED REGION; PROTEIN CBP; CAMP
AB cAMP response element binding protein (CREB) is a key regulator of glucose metabolism and synaptic plasticity that is canonically regulated through recruitment of transcriptional coactivators. Here we show that phosphorylation of CREB on a conserved cluster of Ser residues (the ATM/CK cluster) by the DNA damage-activated protein kinase ataxia-telangiectasia-mutated (ATM) and casein kinase1 (CK1) and casein kinase2 (CK2) positively and negatively regulates CREB-mediated transcription in a signal dependent manner. In response to genotoxic stress, phosphorylation of the ATM/CK cluster inhibited CREB-mediated gene expression, DNA binding activity and chromatin occupancy proportional to the number of modified Ser residues. Paradoxically, substoichiometric, ATM-independent, phosphorylation of the ATM/CK cluster potentiated bursts in CREB-mediated transcription by promoting recruitment of the CREB coactivator, cAMP-regulated transcriptional coactivators (CRTC2). Livers from mice expressing a non-phosphorylatable CREB allele failed to attenuate gluconeogenic genes in response to DNA damage or fully activate the same genes in response to glucagon. We propose that phosphorylation-dependent regulation of DNA binding activity evolved as a tunable mechanism to control CREB transcriptional output and promote metabolic homeostasis in response to rapidly changing environmental conditions.
C1 [Kim, Sang Hwa; Trinh, Anthony T.; Mastrocola, Adam S.; Tibbetts, Randal S.] Univ Wisconsin, Dept Human Oncol, Sch Med & Publ Hlth, Madison, WI 53705 USA.
[Larsen, Michele Campaigne; Jefcoate, Colin R.] Univ Wisconsin, Dept Cell & Regenerat Biol, Sch Med & Publ Hlth, Madison, WI 53705 USA.
[Bushel, Pierre R.] NIEHS, Biostat & Computat Biol Branch, POB 12233, Res Triangle Pk, NC 27709 USA.
RP Tibbetts, RS (reprint author), Univ Wisconsin, Dept Human Oncol, Sch Med & Publ Hlth, Madison, WI 53705 USA.
EM rstibbetts@wisc.edu
FU National Cancer Institute [R01CA180765-01]; National Institute for
Neurological Disorders and Stroke [1R21NS090313-01A1]; National
Institute of Diabetes and Digestive and Kidney diseases [R01DK090249];
Intramural Research Program of the National Institutes of Health [NIH];
National Institute of Environmental Health Sciences [NIEHS]
FX National Cancer Institute [R01CA180765-01 to R.S.T.]; National Institute
for Neurological Disorders and Stroke [1R21NS090313-01A1 to R.S.T.];
National Institute of Diabetes and Digestive and Kidney diseases
[R01DK090249 to C.R.J.]; Intramural Research Program of the National
Institutes of Health [NIH]; National Institute of Environmental Health
Sciences [NIEHS]. Funding for open access charge: National Cancer
Institute [R01CA180765-01].
NR 49
TC 0
Z9 0
U1 1
U2 1
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
EI 1362-4962
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD NOV
PY 2016
VL 44
IS 20
BP 9667
EP 9680
DI 10.1093/nar/gkw643
PG 14
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA EK3HR
UT WOS:000393817800019
PM 27431323
ER
PT J
AU Hao, CX
Gely-Pernot, A
Kervarrec, C
Boudjema, M
Becker, E
Khil, P
Tevosian, S
Jegou, B
Smagulova, F
AF Hao, Chunxiang
Gely-Pernot, Aurore
Kervarrec, Christine
Boudjema, Melissa
Becker, Emmanuelle
Khil, Pavel
Tevosian, Sergei
Jegou, Bernard
Smagulova, Fatima
TI Exposure to the widely used herbicide atrazine results in deregulation
of global tissue-specific RNA transcription in the third generation and
is associated with a global decrease of histone trimethylation in mice
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID EPIGENETIC TRANSGENERATIONAL INHERITANCE; EMBRYONIC STEM-CELLS; MOUSE
SPERMATOZOA; NUCLEAR RECEPTORS; GENE-EXPRESSION; NONCODING RNAS;
MESSENGER-RNA; ORAL-EXPOSURE; GERM-CELLS; MALE-RATS
AB The epigenetic events imposed during germline reprogramming and affected by harmful exposure can be inherited and transferred to subsequent generations via gametes inheritance. In this study, we examine the transgenerational effects promoted by widely used herbicide atrazine (ATZ). We exposed pregnant outbred CD1 female mice and the male progeny was crossed for three generations with untreated females. We demonstrate here that exposure to ATZ affects meiosis, spermiogenesis and reduces the spermatozoa number in the third generation (F3) male mice. We suggest that changes in testis cell types originate from modified transcriptional network in undifferentiated spermatogonia. Importantly, exposure to ATZ dramatically increases the number of transcripts with novel transcription initiation sites, spliced variants and alternative polyadenylation sites. We found the global decrease in H3K4me3 occupancy in the third generationmales. The regions with altered H3K4me3 occupancy in F3 ATZ-derived males correspond to altered H3K4me3 occupancy of F1 generation and 74% of changed peaks in F3 generation are associated with enhancers. The regions with altered H3K4me3 occupancy are enriched in SP family and WT1 transcription factor binding sites. Our data suggest that the embryonic exposure to ATZ affects the development and the changes induced by ATZ are transferred up to three generations.
C1 [Hao, Chunxiang; Gely-Pernot, Aurore; Kervarrec, Christine; Boudjema, Melissa; Becker, Emmanuelle; Jegou, Bernard; Smagulova, Fatima] INSERM, IRSET, U1085, 9 Ave Prof Leon Bernard, F-35000 Rennes, France.
[Jegou, Bernard] EHESP, 2 Ave Prof Leon Bernard, F-35000 Rennes, France.
[Gely-Pernot, Aurore] NIH, Clin Ctr, Bethesda, MD 20892 USA.
[Tevosian, Sergei] Univ Florida, Dept Physiol Sci, Box 100144,1333 Ctr Dr, Gainesville, FL 32610 USA.
RP Smagulova, F (reprint author), INSERM, IRSET, U1085, 9 Ave Prof Leon Bernard, F-35000 Rennes, France.
EM fatima.smagulova@inserm.fr
FU Chair of Excellence program from the European University of Brittany
[11-IRSET]; Atip-Avenir program from INSERM [R13139NS]; China
Scholarship Council Fellowship; Atip-Avenir Fellowship for young
researchers; ATIP-Avenir INSERM [R13139NS]
FX Chair of Excellence program from the European University of Brittany
[11-IRSET] (to F.S.); Atip-Avenir program from INSERM [R13139NS] (to
F.S.); China Scholarship Council Fellowship (to C.H.); Atip-Avenir
Fellowship for young researchers (to A.G.P.). Funding for open access
charge: ATIP-Avenir 2013 INSERM [R13139NS].
NR 132
TC 0
Z9 0
U1 2
U2 2
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
EI 1362-4962
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD NOV
PY 2016
VL 44
IS 20
BP 9784
EP 9802
DI 10.1093/nar/gkw840
PG 19
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA EK3HR
UT WOS:000393817800028
PM 27655631
ER
PT J
AU Sztuba-Solinska, J
Diaz, L
Kumar, MR
Kolb, G
Wiley, MR
Jozwick, L
Kuhn, JH
Palacios, G
Radoshitzky, SR
Le Grice, SFJ
Johnson, RF
AF Sztuba-Solinska, Joanna
Diaz, Larissa
Kumar, Mia R.
Kolb, Gaelle
Wiley, Michael R.
Jozwick, Lucas
Kuhn, Jens H.
Palacios, Gustavo
Radoshitzky, Sheli R.
Le Grice, Stuart F. J.
Johnson, Reed F.
TI A small stem-loop structure of the Ebola virus trailer is essential for
replication and interacts with heat-shock protein A8
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID SELECTIVE 2'-HYDROXYL ACYLATION; RNA SECONDARY STRUCTURES; SINGLE
NUCLEOTIDE RESOLUTION; PRIMER EXTENSION SHAPE; 3' UNTRANSLATED REGION;
TRACT-BINDING-PROTEIN; MESSENGER-RNA; MARBURG-VIRUS; HOST PROTEIN;
HIGH-THROUGHPUT
AB Ebola virus (EBOV) is a single-stranded negative-sense RNA virus belonging to the Filoviridae family. The leader and trailer non-coding regions of the EBOV genome likely regulate its transcription, replication, and progeny genome packaging. We investigated the cis-acting RNA signals involved in RNA-RNA and RNA-protein interactions that regulate replication of eGFP-encoding EBOV minigenomic RNA and identified heat shock cognate protein family A (HSC70) member 8 (HSPA8) as an EBOV trailer-interacting host protein. Mutational analysis of the trailer HSPA8 binding motif revealed that this interaction is essential for EBOV minigenome replication. Selective 2'-hydroxyl acylation analyzed by primer extension analysis of the secondary structure of the EBOVminigenomic RNA indicates formation of a small stem-loop composed of the HSPA8 motif, a 3'-stem-loop (nucleotides 1868-1890) that is similar to a previously identified structure in the replicative intermediate (RI) RNA and a panhandle domain involving a trailer-to-leader interaction. Results ofminigenome assays and an EBOV reverse genetic system rescue support a role for both the panhandle domain and HSPA8 motif 1 in virus replication.
C1 [Sztuba-Solinska, Joanna; Le Grice, Stuart F. J.] NCI, RT Biochem Sect, Basic Res Lab, NIH, Frederick, MD 21702 USA.
[Diaz, Larissa; Kumar, Mia R.; Kolb, Gaelle; Johnson, Reed F.] NIAID, Emerging Viral Pathogens Sect, NIH, Frederick, MD 21702 USA.
[Wiley, Michael R.; Jozwick, Lucas; Palacios, Gustavo; Radoshitzky, Sheli R.] US Army, Med Res Inst Infect Dis, Ft Detrick, MD 21702 USA.
[Kuhn, Jens H.] NIAID, Integrated Res Facil Ft Detrick, NIH, Frederick, MD 21702 USA.
RP Le Grice, SFJ (reprint author), NCI, RT Biochem Sect, Basic Res Lab, NIH, Frederick, MD 21702 USA.; Johnson, RF (reprint author), NIAID, Emerging Viral Pathogens Sect, NIH, Frederick, MD 21702 USA.
EM legrices@mail.nih.gov; johnsonreed@mail.nih.gov
OI Kuhn, Jens H./0000-0002-7800-6045; Palacios, Gustavo/0000-0001-5062-1938
FU NIAID Division of Intramural Research; Intramural Research Program of
the National Cancer Institute, National Institutes of Health, Department
of Health and Human Services; Battelle Memorial Institute's prime
contract; US National Institute of Allergy and Infectious Diseases
(NIAID) [HHSN272200700016I]; The Joint Science and Technology Office for
Chemical and Biological Defense (JSTO-CBD) of the Defense Threat
Reduction Agency (DTRA) [1323839, CB3849]; Defense Threat Reduction
Agency [CB10217]
FX This work was supported by the NIAID Division of Intramural Research.
S.L.G. and J.S.-S. were supported by the Intramural Research Program of
the National Cancer Institute, National Institutes of Health, Department
of Health and Human Services. This work was funded in part through
Battelle Memorial Institute's prime contract with the US National
Institute of Allergy and Infectious Diseases (NIAID) under Contract No.
HHSN272200700016I. A subcontractor to Battelle Memorial Institute who
performed this work is: J.H.K. an employee of Tunnell Government
Services, Inc. S.R.R was supported by The Joint Science and Technology
Office for Chemical and Biological Defense (JSTO-CBD) of the Defense
Threat Reduction Agency (DTRA) (proposal #1323839 and CCAR# CB3849).
Portions of this work performed by S.R.R. and L.J. were funded by the
Defense Threat Reduction Agency, CB10217.
NR 68
TC 0
Z9 0
U1 2
U2 2
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
EI 1362-4962
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD NOV
PY 2016
VL 44
IS 20
BP 9831
EP 9846
DI 10.1093/nar/gkw825
PG 16
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA EK3HR
UT WOS:000393817800031
PM 27651462
ER
PT J
AU Kellner, CH
Husain, MM
Knapp, RG
McCall, WV
Petrides, G
Rudorfer, MV
Young, RC
Sampson, S
McClintock, SM
Mueller, M
Prudic, J
Greenberg, RM
Weiner, RD
Bailine, SH
Rosenquist, PB
Raza, A
Kaliora, S
Latoussakis, V
Tobias, KG
Briggs, MC
Liebman, LS
Geduldig, ET
Teklehaimanot, AA
Lisanby, SH
AF Kellner, Charles H.
Husain, Mustafa M.
Knapp, Rebecca G.
McCall, W. Vaughn
Petrides, Georgios
Rudorfer, Matthew V.
Young, Robert C.
Sampson, Shirlene
McClintock, Shawn M.
Mueller, Martina
Prudic, Joan
Greenberg, Robert M.
Weiner, Richard D.
Bailine, Samuel H.
Rosenquist, Peter B.
Raza, Ahmad
Kaliora, Styliani
Latoussakis, Vassilios
Tobias, Kristen G.
Briggs, Mimi C.
Liebman, Lauren S.
Geduldig, Emma T.
Teklehaimanot, Abeba A.
Lisanby, Sarah H.
CA CORE PRIDE Work Grp
TI Right Unilateral Ultrabrief Pulse ECT in Geriatric Depression: Phase 1
of the PRIDE Study
SO AMERICAN JOURNAL OF PSYCHIATRY
LA English
DT Article
ID TREATMENT-RESISTANT DEPRESSION; ELECTROCONVULSIVE-THERAPY; MAJOR
DEPRESSION; DOUBLE-BLIND; ELECTRODE PLACEMENT; CONTROLLED-TRIAL; RATING
SCALE; PHARMACOTHERAPY; ANTIDEPRESSANT; EFFICACY
AB Objective: The Prolonging Remission in Depressed Elderly (PRIDE) study evaluated the efficacy of right unilateral ultra brief pulse electroconvulsive therapy (ECT) combined with venlafaxine for the treatment of geriatric depression.
Method: PRIDE was a two-phase multisite study. Phase 1 was an acute course of right unilateral ultrabrief pulse ECT, combined with open-label venlafaxine at seven academic medical centers. In phase 2 (reported separately), patients who had remitted were randomly assigned to receive pharmacotherapy (venlafaxine plus lithium) or pharmacotherapy plus continuation ECT. In phase 1, depressed patients received high-dose ECT (at six times the seizure threshold) three times per week. Venlafaxine was started during the first week of treatment and continued throughout the study. The primary outcome measure was remission, assessed with the 24-item Hamilton Depression Rating Scale (HAM-D), which was administered three times per week. Secondary outcome measures were post-ECT reorientation and safety. Paired t tests were used to estimate and evaluate the significance of change from baseline in HAM-D scores.
Results: Of 240 patients who entered phase 1 of the study, 172 completed it. Overall, 61.7% (148/240) of all patients met remission criteria, 10.0% (24/240) did not remit, and 28.3% (68/240) dropped out; 70% (169/240) met response criteria. Among those who remitted, the mean decrease in HAM-D score was 24.7 points (95% CI=23.4, 25.9), with a mean final score of 6.2 (SD-2.5) and an average change from baseline of 79%. The mean number of ECT treatments to remission was 7.3 (SD=3.1).
Conclusions: Right unilateral ultrabrief pulse ECT, combined with venlafaxine, is a rapidly acting and highly effective treatment option for depressed geriatric patients, with excellent safety and tolerability. These data add to the evidence base supporting the efficacy of ECT to treat severe depression in elderly patients.
C1 [Kellner, Charles H.] Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA.
Columbia Univ, Dept Psychiat, New York, NY USA.
New York State Psychiat Inst & Hosp, New York, NY 10032 USA.
NYU, Dept Psychiat & Behav Hlth Sci, Lutheran Med Ctr, New York, NY USA.
Med Univ South Carolina, Dept Publ Hlth Sci, Coll Med, Charleston, SC USA.
Zucker Hillside Hosp North Shore LIJ Hlth Syst, Dept Psychiat, New York, NY USA.
Univ Texas Southwestern Med Ctr Dallas, Dept Psychiat, Dallas, TX USA.
New York Presbyterian Weill Cornell Med Ctr, Dept Psychiat, New York, NY USA.
New York Presbyterian Weill Cornell Med Ctr, Dept Psychiat, White Plains, NY USA.
Duke Univ, Sch Med, Dept Psychiat & Behav Sci, Durham, NC USA.
Augusta Univ, Dept Psychiat & Hlth Behav, Med Coll Georgia, Augusta, GA USA.
Mayo Clin, Coll Med, Dept Psychiat & Psychol, Rochester, MN USA.
NIMH, Div Serv & Intervent Res, Bethesda, MD 20892 USA.
RP Kellner, CH (reprint author), Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA.
EM charles.kellner@mssm.edu
FU NIMH [U01MH055495, U01MH081362, U01MH086127, U01MH086130, U01MH08612005,
U01MH084241, U01MH086122]; Alkermes; Assurex; Avanir; Cyberonics;
Brainsway; MagStim; NARSAD; National Institute of Neurological Disorders
and Stroke; National Institute on Aging; NeoSync; Neuronetics; NIDA;
NIMH; Stanley Foundation; St. Jude Medical (Advanced Neuromodulation
Systems); American Foundation for the Prevention of Suicide and NIMH;
Amgen; AstraZeneca; Corcept; Eli Lilly; Proteus; St. Jude Medical;
Sunovion; Brain and Behavior Research Foundation; Stanley Medical
Research Foundation; Nexstim; NIH
FX Supported by NIMH grants U01MH055495, U01MH081362, U01MH086127,
U01MH086127, U01MH086130, U01MH08612005, U01MH084241, and U01MH086122.;
Dr. Kellner receives honoraria from UpToDate, Psychiatric Times, and
Northwell Health and royalties from Cambridge University Press. Dr.
Husain has received grant support from Alkermes, Assurex, Avanir,
Cyberonics, Brainsway, MagStim, NARSAD, the National Institute of
Neurological Disorders and Stroke, the National Institute on Aging,
NeoSync, Neuronetics, NIDA, NIMH, the Stanley Foundation, and St. Jude
Medical (Advanced Neuromodulation Systems). Dr. McCall has served as a
scientific adviser for Multiple Energy Technologies, and he has received
research support from the American Foundation for the Prevention of
Suicide and NIMH, royalties from Wolters Kluwer, and honoraria from
Anthem, Inc., CME Outfitters, and Global Medical Education. Dr. Petrides
has received research support from Amgen, AstraZeneca, Corcept, Eli
Lilly, Proteus, St. Jude Medical, and Sunovion, and he has served on an
advisory panel for Corcept. Dr. Young is a consultant to NIH and has
received research support from NIMH. Dr. McClintock has received
research support from NIMH and a teaching honorarium from TMS Education
Solutions; he is a member of the editorial board of the Journal of ECT.
Dr. Lisanby has received grant support from the Brain and Behavior
Research Foundation, the Stanley Medical Research Foundation, Neosync,
Nexstim, NIH, and Brainsway; this work was performed while Dr. Lisanby
was at Duke University School of Medicine. The other authors report no
financial relationships with commercial interests.
NR 36
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U1 2
U2 2
PU AMER PSYCHIATRIC PUBLISHING, INC
PI ARLINGTON
PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA
SN 0002-953X
EI 1535-7228
J9 AM J PSYCHIAT
JI Am. J. Psychiat.
PD NOV
PY 2016
VL 173
IS 11
BP 1101
EP 1109
DI 10.1176/appi.ajp.201615081101
PG 9
WC Psychiatry
SC Psychiatry
GA EA2LE
UT WOS:000386423000009
ER
PT J
AU Kellner, CH
Husain, MM
Knapp, RG
McCall, WV
Petrides, G
Rudorfer, MV
Young, RC
Sampson, S
McClintock, SM
Mueller, M
Prudic, J
Greenberg, RM
Weiner, RD
Bailine, SH
Rosenquist, PB
Raza, A
Kaliora, S
Latoussakis, V
Tobias, KG
Briggs, MC
Liebman, LS
Geduldig, ET
Teklehaimanot, AA
Dooley, M
Lisanby, SH
AF Kellner, Charles H.
Husain, Mustafa M.
Knapp, Rebecca G.
McCall, W. Vaughn
Petrides, Georgios
Rudorfer, Matthew V.
Young, Robert C.
Sampson, Shirlene
McClintock, Shawn M.
Mueller, Martina
Prudic, Joan
Greenberg, Robert M.
Weiner, Richard D.
Bailine, Samuel H.
Rosenquist, Peter B.
Raza, Ahmad
Kaliora, Styliani
Latoussakis, Vassilios
Tobias, Kristen G.
Briggs, Mimi C.
Liebman, Lauren S.
Geduldig, Emma T.
Teklehaimanot, Abeba A.
Dooley, Mary
Lisanby, Sarah H.
CA CORE PRIDE Work Grp
TI A Novel Strategy for Continuation ECT in Geriatric Depression: Phase 2
of the PRIDE Study
SO AMERICAN JOURNAL OF PSYCHIATRY
LA English
DT Article
ID RATING-SCALE; ELECTROCONVULSIVE-THERAPY; INTERVIEW; MINI
AB Objective: The randomized phase (phase 2) of the Prolonging Remission in Depressed Elderly (PRIDE) study evaluated the efficacy and tolerability of continuation ECT plus medication compared with medication alone in depressed geriatric patients after a successful course of ECT (phase 1).
Method: PRIDE was a two-phase multisite study. Phase 1 was an acute course of right unilateral ultrabrief pulse ECT, augmented with venlafaxine. Phase 2 compared two randomized treatment arms: a medication only arm (venlafaxine plus lithium, over 24 weeks) and an ECT plus medication arm (four continuation ECTtreatments over1 month, plus additional ECT as needed, using the Symptom-Titrated, Algorithm-Based Longitudinal ECT [STABLE] algorithm, while continuing yenlafaxine plus lithium). The intent-to-treat sample comprised 120 remitters from phase 1. The primary efficacy outcome measure was score on the 24-item Hamilton Depression Rating Scale (HAM-D), and the secondary efficacy outcome was score on the Clinical Global Impressions severity scale (CGI-S). Tolerability as measured by neurocognitive performance (reported elsewhere) was assessed using an extensive test battery; global cognitive functioning as assessed by the Mini-Mental State Examination (MMSE) is reported here. Longitudinal mixed-effects repeated-measures modeling was used to compare ECT plus medication and medication alone for efficacy and global cognitive function outcomes.
Results: At 24 weeks, the ECT plus medication group had statistically significantly lower HAM-D scores than the medication only group. The difference in adjusted mean HAM-D scores at study end was 4.2 (95% CI = 1.6, 6.9). Significantly more patients in the ECT plus medication group were rated "not ill at all" on the CGI-S compared with the medication only group. There was no statistically significant difference between groups in MMSE score.
Conclusions: Additional ECT after remission (here operationalized as four continuation ECT treatments followed by further ECT only as needed) was beneficial in sustaining mood improvement for most patients.
C1 [Kellner, Charles H.] Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA.
Columbia Univ, Dept Psychiat, New York, NY USA.
New York State Psychiat Inst & Hosp, New York, NY 10032 USA.
NYU, Lutheran Med Ctr, Dept Psychiat & Behav Hlth Sci, New York, NY USA.
Med Univ South Carolina, Coll Med, Dept Publ Hlth Sci, Charleston, SC USA.
Zucker Hillside Hosp Northwell Hlth Syst, Dept Psychiat, New York, NY USA.
Univ Texas Southwestern Med Ctr Dallas, Dept Psychiat, Dallas, TX USA.
New York Presbyterian Weill Cornell Med Ctr, Dept Psychiat, New York, NY USA.
New York Presbyterian Weill Cornell Med Ctr, Dept Psychiat, White Plains, NY USA.
Duke Univ, Sch Med, Dept Psychiat & Behav Sci, Durham, NC USA.
Augusta Univ, Med Coll Georgia, Dept Psychiat & Hlth Behav, Augusta, GA USA.
Mayo Clin, Coll Med, Dept Psychiat & Psychol, Rochester, MN USA.
NIMH, Div Serv & Intervent Res, Bethesda, MD 20892 USA.
RP Kellner, CH (reprint author), Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA.
EM charles.kellner@mssm.edu
OI Greenberg, Robert/0000-0001-7078-8970
FU NIMH [U01MH055495, U01MH081362, U01MH086127, U01MH086130, U01MH08612005,
U01MH084241, U01MH086122]; Alkermes; Assurex; Avanir; Cyberonics;
Brainsway; MagStim; NARSAD; National Institute of Neurological Disorders
and Stroke; National Institute on Aging; NeoSync; Neuronetics; NIDA;
NIMH; Stanley Foundation; St. Jude Medical (Advanced Neuromodulation
Systems); American Foundation for the Prevention of Suicide; Amgen;
AstraZeneca; Corcept; Eli Lilly; Proteus; St. Jude Medical; Sunovion;
Brain and Behavior Research Foundation; Stanley Medical Research
Foundation; Nexstim; NIH
FX Supported by NIMH grants U01MH055495, U01MH081362, U01MH086127,
U01MH086127, U01MH086130, U01MH08612005, U01MH084241, and U01MH086122.;
Dr. Kellner receives honoraria from UpToDate, Psychiatnc Times, and
Northwell Health and royalties from Cambridge University Press. Dr.
Husain has received grant support from Alkermes, Assurex, Avanir,
Cyberonics, Brainsway, MagStim, NARSAD, the National Institute of
Neurological Disorders and Stroke, the National Institute on Aging,
NeoSync, Neuronetics, NIDA, NIMH, the Stanley Foundation, and St. Jude
Medical (Advanced Neuromodulation Systems). Dr. McCall has served as a
scientific adviser for Multiple Energy Technologies, and he has received
research support from the American Foundation for the Prevention of
Suicide and NIMH, royalties from Wolters Kluwer, and honoraria from
Anthem, Inc., CME Outfitters, and Global Medical Education. Dr. Petrides
has received research support from Amgen, AstraZeneca, Corcept, Eli
Lilly, Proteus, St. Jude Medical, and Sunovion, and he has served on an
advisory panel for Corcept. Dr. Young is a consultant to NIH and has
received research support from NIMH. Dr McClintock has received research
support from NIMH and a teaching honorarium from TMS Education
Solutions; he is a member of the editorial board of the Journal of ECT.
Dr. Lisanby has received grant support from the Brain and Behavior
Research Foundation, the Stanley Medical Research Foundation, Neosync,
Nexstim, NIH, and Brainsway; this work was performed while Dr. Lisanby
was at Duke University School of Medicine. The other authors report no
financial relationships with commercial interests.
NR 16
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U1 0
U2 0
PU AMER PSYCHIATRIC PUBLISHING, INC
PI ARLINGTON
PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA
SN 0002-953X
EI 1535-7228
J9 AM J PSYCHIAT
JI Am. J. Psychiat.
PD NOV
PY 2016
VL 173
IS 11
BP 1110
EP 1118
DI 10.1176/appi.ajp.2016.16010118
PG 9
WC Psychiatry
SC Psychiatry
GA EA2LE
UT WOS:000386423000010
ER
PT J
AU Loucks, EB
Huang, YT
Agha, G
Chu, S
Eaton, CB
Gilman, SE
Buka, SL
Kelsey, KT
AF Loucks, Eric B.
Huang, Yen-Tsung
Agha, Golareh
Chu, Su
Eaton, Charles B.
Gilman, Stephen E.
Buka, Stephen L.
Kelsey, Karl T.
TI Epigenetic Mediators Between Childhood Socioeconomic Disadvantage and
Mid-Life Body Mass Index: The New England Family Study
SO PSYCHOSOMATIC MEDICINE
LA English
DT Article
DE DNA methylation; epigenetics; adiposity; body mass index; socioeconomic
disadvantage; socioeconomic status
ID EARLY-LIFE ORIGINS; EPIGENOME-WIDE ASSOCIATION; WNT SIGNALING PATHWAY;
DNA METHYLATION DATA; ADIPOSE-TISSUE; STRESS REACTIVITY;
PERIPHERAL-BLOOD; GENE-EXPRESSION; OBESITY; CORTISOL
AB Objective: Childhood socioeconomic disadvantage is associated with adulthood obesity risk; however, epigenetic mechanisms are poorly understood. This work's objective was to evaluate whether associations of childhood socioeconomic disadvantage with adulthood body mass index (BMI) are mediated by DNA methylation.
Methods: Participants were 141 men and women from the New England Family Study, prospectively followed prenatally through a mean age of 47 years. Epigenomewide DNA methylation was evaluated in peripheral blood and adipose tissue obtained at adulthood, using the Infinium HumanMethylation450K BeadChip. Childhood socioeconomic status (SES) at age 7 years was assessed directly from parents' reports. Offspring adiposity was directly assessed using BMI at a mean age of 47 years. Associations of SES, DNA methylation, and BMI were estimated using least square estimators. Statistical mediation analyses were performed using joint significance test and bootstrapping.
Results: Of CpG sites significant at the 25% false discovery rate level in epigenomewide methylation BMI analyses, 91 sites in men and 71 sites in women were additionally significant for SES-methylation associations (p < .001) in adipose tissue. Many involved genes biologically relevant for development of obesity, including fatty acid synthase, transmembrane protein 88, signal transducer and activator of transcription 3, and neuritin 1. There was no evidence of epigenetic mediation in peripheral blood leukocytes.
Conclusions: DNA methylation at specific genes may be mediators of associations between childhood socioeconomic disadvantage and mid-life BMI in adipose tissue. Findings motivate continued efforts to study if and how childhood socioeconomic disadvantage is biologically embedded at the level of the epigenome in regions etiologically relevant for adiposity.
C1 [Loucks, Eric B.; Huang, Yen-Tsung; Chu, Su; Eaton, Charles B.; Buka, Stephen L.; Kelsey, Karl T.] Brown Univ, Sch Publ Hlth, Dept Epidemiol, 121 South Main St, Providence, RI 02912 USA.
[Agha, Golareh] Harvard TH Chan Sch Publ Hlth, Dept Environm Hlth, Boston, MA USA.
[Eaton, Charles B.] Brown Univ, Warren Alpert Med Sch, Dept Family Med, Providence, RI 02912 USA.
[Gilman, Stephen E.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Hlth Behav Branch, Div Intramural Populat Hlth Res, Rockville, MD USA.
[Gilman, Stephen E.] Harvard TH Chan Sch Publ Hlth, Dept Social & Behav Sci, Boston, MA USA.
[Gilman, Stephen E.] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.
RP Loucks, EB (reprint author), Brown Univ, Sch Publ Hlth, Dept Epidemiol, 121 South Main St, Providence, RI 02912 USA.
EM eric.loucks@brown.edu
FU NIH/NIA [RC2AG036666, R01AG048825]; Intramural Research Program of the
Eunice Kennedy Shriver National Institute of Child Health and Human
Development
FX Funding for this study was provided by NIH/NIA grants RC2AG036666 and
R01AG048825, and by the Intramural Research Program of the Eunice
Kennedy Shriver National Institute of Child Health and Human
Development. The authors report no conflicts of interest.
NR 74
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U1 6
U2 6
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0033-3174
EI 1534-7796
J9 PSYCHOSOM MED
JI Psychosom. Med.
PD NOV-DEC
PY 2016
VL 78
IS 9
BP 1053
EP 1065
DI 10.1097/PSY.0000000000000411
PG 13
WC Psychiatry; Psychology; Psychology, Multidisciplinary
SC Psychiatry; Psychology
GA EE5LR
UT WOS:000389649600009
PM 27768648
ER
PT J
AU Li, H
Zhu, YT
Burnside, ES
Drukker, K
Hoadley, KA
Fan, C
Conzen, SD
Whitman, GJ
Sutton, EJ
Net, JM
Ganott, M
Huang, E
Morris, EA
Perou, CM
Ji, Y
Giger, ML
AF Li, Hui
Zhu, Yitan
Burnside, Elizabeth S.
Drukker, Karen
Hoadley, Katherine A.
Fan, Cheng
Conzen, Suzanne D.
Whitman, Gary J.
Sutton, Elizabeth J.
Net, Jose M.
Ganott, Marie
Huang, Erich
Morris, Elizabeth A.
Perou, Charles M.
Ji, Yuan
Giger, Maryellen L.
TI MR Imaging Radiomics Signatures for Predicting the Risk of Breast Cancer
Recurrence as Given by Research Versions of MammaPrint, Oncotype DX, and
PAM50 Gene Assays
SO RADIOLOGY
LA English
DT Article
ID MAXIMUM-LIKELIHOOD-ESTIMATION; BINORMAL ROC CURVES; COMPUTERIZED
ANALYSIS; PROGNOSTIC MARKERS; DCE-MRI; LESIONS; EXPRESSION; IMAGES;
DIAGNOSIS; SUBTYPES
AB Purpose: To investigate relationships between computer-extracted breast magnetic resonance (MR) imaging phenotypes with multigene assays of MammaPrint, Oncotype DX, and PAM50 to assess the role of radiomics in evaluating the risk of breast cancer recurrence.
Materials and Methods: Analysis was conducted on an institutional review board-approved retrospective data set of 84 deidentified, multi-institutional breast MR examinations from the National Cancer Institute Cancer Imaging Archive, along with clinical, histopathologic, and genomic data from The Cancer Genome Atlas. The data set of biopsy-proven invasive breast cancers included 74 (88%) ductal, eight (10%) lobular, and two (2%) mixed cancers. Of these, 73 (87%) were estrogen receptor positive, 67 (80%) were progesterone receptor positive, and 19 (23%) were human epidermal growth factor receptor 2 positive. For each case, computerized radiomics of the MR images yielded computer-extracted tumor phenotypes of size, shape, margin morphology, enhancement texture, and kinetic assessment. Regression and receiver operating characteristic analysis were conducted to assess the predictive ability of the MR radiomics features relative to the multigene assay classifications.
Results: Multiple linear regression analyses demonstrated significant associations (R-2 = 0.25-0.32, r = 0.5-0.56, P < .0001) between radiomics signatures and multigene assay recurrence scores. Important radiomics features included tumor size and enhancement texture, which indicated tumor heterogeneity. Use of radiomics in the task of distinguishing between good and poor prognosis yielded area under the receiver operating characteristic curve values of 0.88 (standard error, 0.05), 0.76 (standard error, 0.06), 0.68 (standard error, 0.08), and 0.55 (standard error, 0.09) for MammaPrint, Oncotype DX, PAM50 risk of relapse based on subtype, and PAM50 risk of relapse based on subtype and proliferation, respectively, with all but the latter showing statistical difference from chance.
Conclusion: Quantitative breast MR imaging radiomics shows promise for image-based phenotyping in assessing the risk of breast cancer recurrence. (C) RSNA, 2016
C1 [Li, Hui; Drukker, Karen; Giger, Maryellen L.] Univ Chicago, Dept Radiol, 5841 S Maryland Ave,MC 2026, Chicago, IL 60637 USA.
[Ji, Yuan] Univ Chicago, Dept Publ Hlth Sci, 5841 S Maryland Ave,MC 2026, Chicago, IL 60637 USA.
[Zhu, Yitan; Ji, Yuan] NorthShore Univ HealthSystem, Program Computat Gen & Med, Evanston, IL 60201 USA.
[Burnside, Elizabeth S.] Univ Wisconsin, Dept Biol, Madison, WI 53706 USA.
[Hoadley, Katherine A.; Fan, Cheng; Perou, Charles M.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC USA.
[Conzen, Suzanne D.] Univ Chicago, Dept Med, Sect Hematol & Oncol, Chicago, IL 60637 USA.
[Whitman, Gary J.] Univ Texas MD Anderson Canc Ctr, Dept Diagnost Radiol, Houston, TX 77030 USA.
[Sutton, Elizabeth J.; Morris, Elizabeth A.] Mem Sloan Kettering Canc Ctr, Dept Radiol, New York, NY 10021 USA.
[Net, Jose M.] Univ Miami, Sylvester Comprehens Canc Ctr, Dept Radiol, Miami, FL USA.
[Ganott, Marie] Univ Pittsburgh, Med Ctr, Dept Radiol, Pittsburgh, PA USA.
[Huang, Erich] NCI, Div Canc Treatment & Diag, Biometr Res Branch, Bethesda, MD USA.
RP Giger, ML (reprint author), Univ Chicago, Dept Radiol, 5841 S Maryland Ave,MC 2026, Chicago, IL 60637 USA.
EM m-giger@uchicago.edu
OI Perou, Charles/0000-0001-9827-2247
FU National Cancer Institute [U01-CA195564, P30-CA14599, P50-CA58223,
U24-CA143848-05]; Breast Cancer Research Foundation grant; Univ of
Chicago Pritzker School of Medicine Dean Bridge Fund
FX Supported by the National Cancer Institute (U01-CA195564, P30-CA14599,
P50-CA58223, and U24-CA143848-05); a Breast Cancer Research Foundation
grant; and The Univ of Chicago Pritzker School of Medicine Dean Bridge
Fund.
NR 39
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U1 6
U2 6
PU RADIOLOGICAL SOC NORTH AMERICA
PI OAK BROOK
PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA
SN 0033-8419
J9 RADIOLOGY
JI Radiology
PD NOV
PY 2016
VL 281
IS 2
BP 382
EP 391
DI 10.1148/radiol.2016152110
PG 10
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA EJ4PL
UT WOS:000393199200006
PM 27144536
ER
PT J
AU Meehan, RS
Chen, AP
Doroshow, JH
AF Meehan, Robert S.
Chen, Alice P.
Doroshow, James H.
TI Role of adaptive randomization in developing novel therapies for
patients with breast cancer
SO TRANSLATIONAL CANCER RESEARCH
LA English
DT Editorial Material
ID BRCA MUTATION CARRIERS; POLY(ADP-RIBOSE) POLYMERASE; CLINICAL-TRIALS;
PARP INHIBITORS; PHASE-2 TRIAL; COMBINATION; CARBOPLATIN; OVARIAN;
TUMORS
C1 [Meehan, Robert S.; Chen, Alice P.; Doroshow, James H.] NCI, Div Canc Treatment & Diag, NIH, Rom 3A-44,Bldg 31,31 Ctr Dr, Bethesda, MD 20892 USA.
[Doroshow, James H.] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Doroshow, JH (reprint author), NCI, Div Canc Treatment & Diag, NIH, Rom 3A-44,Bldg 31,31 Ctr Dr, Bethesda, MD 20892 USA.
EM doroshoj@mail.nih.gov
FU National Cancer Institute, National Institutes of Health
FX This project was funded with federal funds from the National Cancer
Institute, National Institutes of Health. The content of this
publication does not necessarily reflect the views or policies of the US
Department of Health and Human Services.
NR 21
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U1 0
U2 0
PU AME PUBL CO
PI SHEUNG WAN
PA ROOM 604 6-F HOLLYWOOD CENTER, 77-91, QUEENS ROAD, SHEUNG WAN, HONG KONG
00000, PEOPLES R CHINA
SN 2218-676X
EI 2219-6803
J9 TRANSL CANCER RES
JI Transl. Cancer Res.
PD NOV
PY 2016
VL 5
SU 6
BP S1119
EP S1122
DI 10.21037/tcr.2016.11.27
PG 4
WC Oncology
SC Oncology
GA EJ6KM
UT WOS:000393328100023
ER
PT J
AU Rath, BH
Camphausen, K
Tofilon, PJ
AF Rath, Barbara H.
Camphausen, Kevin
Tofilon, Philip J.
TI Glioblastoma radiosensitization by pimozide
SO TRANSLATIONAL CANCER RESEARCH
LA English
DT Editorial Material
ID VALPROIC ACID; CELL-LINES; STEM-CELL; TARGET; INHIBITORS; TEMOZOLOMIDE;
PHENOTYPE; RADIATION; THERAPY; TUMORS
C1 [Rath, Barbara H.; Camphausen, Kevin; Tofilon, Philip J.] NCI, Radiat Oncol Branch, 10 Ctr Dr,MSC 1002,Bldg 10,B3B69B, Bethesda, MD 20892 USA.
RP Tofilon, PJ (reprint author), NCI, Radiat Oncol Branch, 10 Ctr Dr,MSC 1002,Bldg 10,B3B69B, Bethesda, MD 20892 USA.
EM philip.tofilon@nih.gov
NR 24
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U1 0
U2 0
PU AME PUBL CO
PI SHEUNG WAN
PA ROOM 604 6-F HOLLYWOOD CENTER, 77-91, QUEENS ROAD, SHEUNG WAN, HONG KONG
00000, PEOPLES R CHINA
SN 2218-676X
EI 2219-6803
J9 TRANSL CANCER RES
JI Transl. Cancer Res.
PD NOV
PY 2016
VL 5
SU 6
BP S1029
EP S1032
DI 10.21037/tcr.2016.11.17
PG 4
WC Oncology
SC Oncology
GA EJ6KM
UT WOS:000393328100001
ER
PT J
AU Schmidt, KT
Figg, WD
AF Schmidt, Keith T.
Figg, William D.
TI The potential role of curcumin in prostate cancer: the importance of
optimizing pharmacokinetics in clinical studies
SO TRANSLATIONAL CANCER RESEARCH
LA English
DT Editorial Material
ID ANDROGEN RECEPTOR; PHASE-II; DOCETAXEL; ANALOGS; NANOPARTICLES;
PREDNISONE; ASC-J9(R); GROWTH; ENZALUTAMIDE; MITOXANTRONE
C1 [Schmidt, Keith T.; Figg, William D.] NCI, Clin Pharmacol Program, Off Clin Director, Ctr Canc Res,NIH, Bethesda, MD 20892 USA.
[Figg, William D.] NCI, Mol Pharmacol Sect, Genitourinary Malignancies Branch, Ctr Canc Res,NIH, 9000 Rockville Pike,Bldg 10,Room 5A01, Bethesda, MD 20892 USA.
RP Figg, WD (reprint author), NCI, Mol Pharmacol Sect, Genitourinary Malignancies Branch, Ctr Canc Res,NIH, 9000 Rockville Pike,Bldg 10,Room 5A01, Bethesda, MD 20892 USA.
EM figgw@helix.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. 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
organization imply endorsement by the US Government.
NR 25
TC 0
Z9 0
U1 1
U2 1
PU AME PUBL CO
PI SHEUNG WAN
PA ROOM 604 6-F HOLLYWOOD CENTER, 77-91, QUEENS ROAD, SHEUNG WAN, HONG KONG
00000, PEOPLES R CHINA
SN 2218-676X
EI 2219-6803
J9 TRANSL CANCER RES
JI Transl. Cancer Res.
PD NOV
PY 2016
VL 5
SU 6
BP S1107
EP S1110
DI 10.21037/tcr.2016.11.04
PG 4
WC Oncology
SC Oncology
GA EJ6KM
UT WOS:000393328100020
ER
PT J
AU Bektas, A
Sen, R
Ferrucci, L
AF Bektas, Arsun
Sen, Ranjan
Ferrucci, Luigi
TI Does a bit of alcohol turn off inflammation and improve health?
SO AGE AND AGEING
LA English
DT Editorial Material
ID C-REACTIVE PROTEIN; CONSUMPTION; MARKERS; FRAILTY; DISEASE; COHORT;
WOMEN; DIET
C1 [Ferrucci, Luigi] NIA, Translat Gerontol Branch, NIH, Baltimore, MD 21224 USA.
NIA, Lab Mol Biol & Immunol, NIH, Baltimore, MD 21224 USA.
RP Ferrucci, L (reprint author), NIA, Translat Gerontol Branch, NIH, Baltimore, MD 21224 USA.
EM ferruccilu@grc.nia.nih.gov
NR 18
TC 1
Z9 1
U1 0
U2 0
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0002-0729
EI 1468-2834
J9 AGE AGEING
JI Age Ageing
PD NOV
PY 2016
VL 45
IS 6
BP 747
EP 748
DI 10.1093/ageing/afw146
PG 2
WC Geriatrics & Gerontology
SC Geriatrics & Gerontology
GA EI7RY
UT WOS:000392702200003
PM 27555047
ER
PT J
AU Teras, LR
DeSantis, CE
Cerhan, JR
Morton, LM
Jemal, A
Flowers, CR
AF Teras, Lauren R.
DeSantis, Carol E.
Cerhan, James R.
Morton, Lindsay M.
Jemal, Ahmedin
Flowers, Christopher R.
TI 2016 US Lymphoid Malignancy Statistics by World Health Organization
Subtypes
SO CA-A CANCER JOURNAL FOR CLINICIANS
LA English
DT Article
DE chronic lymphocytic leukemia; epidemiology; Hodgkin disease; multiple
myeloma; non-Hodgkin lymphoma
ID NON-HODGKIN-LYMPHOMA; CHRONIC LYMPHOCYTIC-LEUKEMIA; ACUTE
LYMPHOBLASTIC-LEUKEMIA; GENOME-WIDE ASSOCIATION; UNITED-STATES;
BURKITT-LYMPHOMA; RISK-FACTORS; DESCRIPTIVE EPIDEMIOLOGY; INCIDENCE
PATTERNS; CIGARETTE-SMOKING
AB Collectively, lymphoid neoplasms are the fourth most common cancer and the sixth leading cause of cancer death in the United States. The authors provide contemporary lymphoid neoplasm statistics by subtype based on the 2008 World Health Organization classifications, including the most current US incidence and survival data. Presented for the first time are estimates of the total numbers of US lymphoid neoplasm cases by subtype as well as a detailed evaluation of incidence and survival statistics. In 2016, 136,960 new lymphoid neoplasms are expected. Overall lymphoma incidence rates have declined in recent years, but trends vary by subtype. Precursor lymphoid neoplasm incidence rates increased from 2001 to 2012, particularly for B-cell neoplasms. Among the mature lymphoid neoplasms, the fastest increase was for plasma cell neoplasms. Rates also increased for mantle cell lymphoma (males), marginal zone lymphoma, hairy cell leukemia, and mycosis fungoides. Like incidence, survival for both mature T-cell lymphomas and mature B-cell lymphomas varied by subtype and by race. Patients with peripheral T-cell lymphomas had among the worst 5-year relative survival (36%-56%, depending on race/sex), while those with mycosis fungoides had among the best survival (79%-92%). For B-cell lymphomas, 5-year survival ranged from 83% to 91% for patients with marginal zone lymphoma and from 78% to 92% for those with hairy cell leukemia; but the rates were as low as 47% to 63% for patients with Burkitt lymphoma and 44% to 48% for those with plasma cell neoplasms. In general, black men had the lowest survival across lymphoid malignancy subtypes. These contemporary incidence and survival statistics are useful for developing management strategies for these cancers and can offer clues regarding their etiology. (C) 2016 American Cancer Society.
C1 [Teras, Lauren R.] Amer Canc Soc, Hematol Canc Res, Epidemiol Res Program, 250 Williams St NW, Atlanta, GA 30303 USA.
[DeSantis, Carol E.] Amer Canc Soc, Breast & Gynecol Canc Surveillance, Surveillance & Hlth Serv Res, Atlanta, GA 30329 USA.
[Cerhan, James R.] Mayo Clin, Dept Hlth Sci Res, Rochester, MN USA.
[Morton, Lindsay M.] NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD USA.
[Jemal, Ahmedin] Amer Canc Soc, Surveillance & Hlth Serv Res, Atlanta, GA 30329 USA.
[Flowers, Christopher R.] Emory Univ, Winship Canc Inst, Dept Hematol & Oncol, Lymphoma Program, Atlanta, GA 30322 USA.
RP Teras, LR (reprint author), Amer Canc Soc, Hematol Canc Res, Epidemiol Res Program, 250 Williams St NW, Atlanta, GA 30303 USA.
EM lauren.teras@cancer.org
RI Flowers, Christopher/F-1953-2010
OI Flowers, Christopher/0000-0002-9524-3990
FU Spectrum; Celgene; Optum Rx; Seattle Genetics;
Genentech/Biogen-Idec/Roche and Millennium/Takeda; Abbvie; Acerta;
Gilead Sciences; Infinity Pharmaceuticals; Millennium/Takeda; Onyx
Pharmaceuticals; National Cancer Institute/National Institutes of
Health; Borroughs Wellcome Fund; V Foundation; Clinical Care Options;
Educational Concepts; PRIME Oncology; Research to Practice
FX Christopher R. Flowers reports consulting fees from Spectrum, Celgene,
Optum Rx, and Seattle Genetics; unpaid consultancy work for
Genentech/Biogen-Idec/Roche and Millennium/Takeda; institutional
research funding/grants from Abbvie, Acerta, Celgene, Gilead Sciences,
Infinity Pharmaceuticals, Millennium/Takeda, Spectrum, Onyx
Pharmaceuticals, the National Cancer Institute/National Institutes of
Health, the Borroughs Wellcome Fund, and The V Foundation; and personal
fees for developing educational presentations from Clinical Care
Options, Educational Concepts, PRIME Oncology, and Research to Practice,
all outside the submitted work. All remaining authors report no
conflicts of interest.
NR 70
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Z9 2
U1 3
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0007-9235
EI 1542-4863
J9 CA-CANCER J CLIN
JI CA-Cancer J. Clin.
PD NOV-DEC
PY 2016
VL 66
IS 6
BP 443
EP 459
DI 10.3322/caac.21357
PG 17
WC Oncology
SC Oncology
GA EI8KR
UT WOS:000392755800003
ER
PT J
AU Harada, T
Nakamura, Y
Sato, K
Nagaya, T
Choyke, PL
Seto, Y
Kobayashi, H
AF Harada, Toshiko
Nakamura, Yuko
Sato, Kazuhide
Nagaya, Tadanobu
Choyke, Peter L.
Seto, Yasuyuki
Kobayashi, Hisataka
TI Surgical tissue handling methods to optimize ex vivo fluorescence with
the activatable optical probe -glutamyl hydroxymethyl rhodamine green
SO Contrast Media & Molecular Imaging
LA English
DT Article
DE optical navigation surgery; fluorescent probe; surgical specimen;
-glutamyl transpeptidase; ovarian cancer
ID ADAPTED BETA-GALACTOSIDASE; MOLECULAR PROBES; DRUG-RESISTANCE;
OVARIAN-CANCER; TRANSPEPTIDASE; TRANSFERASE; EXPRESSION; TUMORS;
PURIFICATION; CLONING
AB Optical fluorescence imaging has been developed as an aid to intraoperative diagnosis to improve surgical and endoscopic procedures. Compared with other intraoperative imaging methods, it is lower in cost, has a high safety margin, is portable and easy to use. -glutamyl hydroxymethyl rhodamine green (gGlu-HMRG) is a recently developed activatable fluorescence probe that emits strong fluorescence in the presence of the enzyme -glutamyl transpeptidase (GGT), which is overexpressed in many cancers, including ovarian cancer. Ex vivo testing is important for clinical approval of such probes. The diagnostic performance of gGlu-HMRG in fresh excised surgical specimens has been reported; however, details of tissue handling have not been optimized. In this study, we investigated four different tissue handling procedures to optimize imaging in excised tumor specimens. The fluorescence intensity time courses after the different tissue handling methods were compared. Additionally, the fluorescence positive areas were correlated with the presence of red fluorescent protein (RFP) in an RFP positive cell line as the standard of reference for cancer location. In the intact' groups, tumors yielded quick and homogeneous activation of gGlu-HMRG. In the rinse' and cut' groups, the fluorescence intensity of the tumor was a little lower than that in the intact group. In the pressed' groups, however, fluorescence intensity from gGlu-HMRG was lower over the entire time course, suggesting a decrease or relocation of excreted GGT. In conclusion, we demonstrate that the method of tissue handling prior to ex vivo imaging with the activatable probe gGlu-HMRG has a strong influence on the signal derived from the specimen. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.
C1 [Harada, Toshiko; Nakamura, Yuko; Sato, Kazuhide; Nagaya, Tadanobu; Choyke, Peter L.; Kobayashi, Hisataka] NCI, Mol Imaging Program, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Seto, Yasuyuki] Univ Tokyo, Grad Sch Med, Dept Stomach & Esophageal Surg, Tokyo 113, Japan.
RP Kobayashi, H (reprint author), NCI, Mol Imaging Program, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM Kobayash@mail.nih.gov
NR 25
TC 1
Z9 1
U1 5
U2 5
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1555-4309
EI 1555-4317
J9 CONTRAST MEDIA MOL I
JI Contrast Media Mol. Imaging
PD NOV-DEC
PY 2016
VL 11
IS 6
BP 572
EP 578
DI 10.1002/cmmi.1705
PG 7
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA EI8LJ
UT WOS:000392757600015
PM 27444370
ER
PT J
AU Pletnev, VZ
Pletneva, NV
Efremov, RG
Goryacheva, EA
Artemyev, IV
Arkhipova, SF
Sarkisyan, KS
Mishin, AS
Lukyanov, KA
Pletnev, SV
AF Pletnev, V. Z.
Pletneva, N. V.
Efremov, R. G.
Goryacheva, E. A.
Artemyev, I. V.
Arkhipova, S. F.
Sarkisyan, K. S.
Mishin, A. S.
Lukyanov, K. A.
Pletnev, S. V.
TI Three-dimensional structure of a pH-dependent fluorescent protein WasCFP
with a tryptophan based deprotonated chromophore
SO RUSSIAN JOURNAL OF BIOORGANIC CHEMISTRY
LA English
DT Article
DE crystal structure; green fluorescent protein WasCFP; Trp based
chromophore; Trp anionic form
ID GREEN; MODE; FRET
AB WasCFP, a pH-dependent green fluorescent protein with a tryptophan-based chromophore (Thr65-Trp66-Gly67) in anionic state, was designed from a cyan precursor mCerulean. In this study, the three-dimensional structure of WasCFP has been determined by an X-ray method at pH 5.5, pH 8.0 and pH 10.0, with a resolution of 1.14, 1.25 and 1.5 , respectively. We show that changes in the acidity of the media are accompanied by a synchronous change of the side chain conformations of the residues in the near-chromophore environment. Subsequent changes in the local H-bond network interacting with the chromophore lead to considerable alterations in the protein spectral properties as a consequence of reversible processes of ionization-protonation of the Trp chromophore. These experimental results have been supported by quantum chemistry calculations.
C1 [Pletnev, V. Z.; Pletneva, N. V.; Efremov, R. G.; Goryacheva, E. A.; Artemyev, I. V.; Arkhipova, S. F.; Sarkisyan, K. S.; Mishin, A. S.; Lukyanov, K. A.] Russian Acad Sci, Shemyakin Ovchinnikov Inst Bioorgan Chem, Moscow, Russia.
[Pletnev, S. V.] NCI, Synchrotron Radiat Res Sect, Macromol Crystallog Lab, Argonne, IL 60439 USA.
RP Pletnev, VZ (reprint author), Russian Acad Sci, Shemyakin Ovchinnikov Inst Bioorgan Chem, Moscow, Russia.
EM vzpletnev@gmail.com
FU Molecular and Cellular Biology fund of the Russian Academy of Sciences;
Russian Foundation for Basic Research grant [14-04-00004]; Russian
Science Foundation [14-24-00118]; Russian Federation [MK-7495.2016.4];
US Department of Energy [W-31-109-Eng-38]; NIH National Cancer Institute
[HHSN261200800001E]
FX X-ray diffraction studies of WasCFP at different pH values were
performed with financial support of the Molecular and Cellular Biology
fund of the Russian Academy of Sciences, and Russian Foundation for
Basic Research grant 14-04-00004. Determination of the WasCFP spatial
structure at physiological pH was carried out within the framework of
the graduate research program. Quantum chemical calculations were
carried out with the support of the Russian Science Foundation (grant
14-24-00118). Work on protein purification was carried out with the
support of a grant by the President of the Russian Federation
(MK-7495.2016.4) with a partial use of the equipment at the Institute of
Bioorganic Chemistry of the Russian Academy of Sciences. X-ray
experimental data were obtained on a station (22 ID) of the synchrotron
center (APS; Argonne, United States). Work at the APS center was
supported by the US Department of Energy under the contract
W-31-109-Eng-38, and, in part, by the contract funded by the NIH
National Cancer Institute HHSN261200800001E.
NR 24
TC 0
Z9 0
U1 0
U2 0
PU MAIK NAUKA/INTERPERIODICA/SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013-1578 USA
SN 1068-1620
EI 1608-330X
J9 RUSS J BIOORG CHEM+
JI Russ. J. Bioorg. Chem.
PD NOV
PY 2016
VL 42
IS 6
BP 612
EP 618
DI 10.1134/S1068162016050149
PG 7
WC Biochemistry & Molecular Biology; Chemistry, Organic
SC Biochemistry & Molecular Biology; Chemistry
GA EJ2MO
UT WOS:000393044600004
ER
PT J
AU Xu, XZ
Li, R
Chen, GZ
Hoopes, SL
Zeldin, DC
Wang, DW
AF Xu, Xizhen
Li, Rui
Chen, Guangzhi
Hoopes, Samantha L.
Zeldin, Darryl C.
Wang, Dao Wen
TI The Role of Cytochrome P450 Epoxygenases, Soluble Epoxide Hydrolase, and
Epoxyeicosatrienoic Acids in Metabolic Diseases
SO ADVANCES IN NUTRITION
LA English
DT Review
DE cytochrome P450 (CYP) epoxygenase; epoxyeicosatrienoic acid; soluble
epoxide hydrolase; insulin resistance; lipid; obesity; type 2 diabetes
ID HIGH-FAT DIET; ENDOPLASMIC-RETICULUM STRESS; REDUCES INSULIN-RESISTANCE;
FRUCTOSE-TREATED RATS; INDUCED DIABETIC MICE; CARDIOVASCULAR-DISEASE;
VASCULAR DYSFUNCTION; ENDOTHELIAL-CELLS; ADIPOSE-TISSUE; LIVER-DISEASE
AB Metabolic diseases are associated with an increased risk of developing cardiovascular disease. The features comprising metabolic diseases include obesity, insulin resistance, hyperglycemia, hyperlipidemia, and hypertension. Recent evidence has emerged showcasing a role for cytochrome P450 epoxygenases, soluble epoxide hydrolase, and epoxyeicosatrienoic acids (EETs) in the development and progression of metabolic diseases. This review discusses the current knowledge related to the modulation of cytochrome P450 epoxygenases and soluble epoxide hydrolase to alter concentrations of biologically active EETs, resulting in effects on insulin resistance, lipid metabolism, obesity, and diabetes. Future areas of research to address current deficiencies in the understanding of these enzymes and their eicosanoid metabolites in various aspects of metabolic diseases are also discussed.
C1 [Xu, Xizhen; Li, Rui; Chen, Guangzhi; Wang, Dao Wen] Huazhong Univ Sci & Technol, Tongji Med Coll, Tongji Hosp, Dept Internal Med, Wuhan, Peoples R China.
[Xu, Xizhen; Li, Rui; Chen, Guangzhi; Wang, Dao Wen] Huazhong Univ Sci & Technol, Tongji Med Coll, Tongji Hosp, Inst Hypertens, Wuhan, Peoples R China.
[Hoopes, Samantha L.; Zeldin, Darryl C.] NIEHS, Div Intramural Res, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.
RP Wang, DW (reprint author), Huazhong Univ Sci & Technol, Tongji Med Coll, Tongji Hosp, Dept Internal Med, Wuhan, Peoples R China.; Wang, DW (reprint author), Huazhong Univ Sci & Technol, Tongji Med Coll, Tongji Hosp, Inst Hypertens, Wuhan, Peoples R China.
EM dwwang@tjh.tjmu.edu.cn
FU National Natural Science Foundation of China [81100085, 81471021,
91439203, 31130031]; Intramural Research Division of the NIH, National
Institute of Environmental Health Sciences [Z01 ES025034]
FX Supported by grants from the National Natural Science Foundation of
China (81100085, 81471021, 91439203, and 31130031). Also supported in
part by the Intramural Research Division of the NIH, National Institute
of Environmental Health Sciences (Z01 ES025034).
NR 67
TC 0
Z9 0
U1 3
U2 3
PU AMER SOC NUTRITION-ASN
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 2161-8313
EI 2156-5376
J9 ADV NUTR
JI Adv. Nutr.
PD NOV
PY 2016
VL 7
IS 6
BP 1122
EP 1128
DI 10.3945/an.116.012245
PG 7
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA EI1ZE
UT WOS:000392284700012
PM 28140329
ER
PT J
AU Pongpiachan, S
AF Pongpiachan, Siwatt
TI Incremental Lifetime Cancer Risk of PM2.5 Bound Polycyclic Aromatic
Hydrocarbons (PAHs) Before and After the Wildland Fire Episode
SO AEROSOL AND AIR QUALITY RESEARCH
LA English
DT Article
DE Wildland fire; PAHs; Northern Thailand; PM2.5; Incremental lifetime
cancer risk
ID EQUIVALENCY FACTORS TEFS; VERTICAL-DISTRIBUTION; PARTICULATE MATTER;
CHEMICAL CHARACTERISTICS; ATMOSPHERIC PARTICLES; SEASONAL-VARIATION;
TRAFFIC EMISSIONS; SIZE DISTRIBUTION; DRY DEPOSITION; CENTRAL TAIWAN
AB In Northern Thailand, wildland fire during cold period releases large amounts of smoke and fine particles into the atmosphere. The fine particles include several persistent organic compounds such as PAHs. In this study, PM2.5-bound PAH concentrations in the air of nine administrative provinces, namely Chiang-Mai, Chiang-Rai, Nan, Phayao, Mae Hong Son, Phrae, Lampang, Lamphun, Uttaradit (N Thailand) were determined during the wildland fire and non-wildland fire seasons. The monitoring strategy comprised two campaigns in each season. PM2.5 was collected using MiniVolTM portable air samplers (Airmetrics) with quartz fibre filters. Both PAHs and their B[a] P-Equivalent concentrations of other urban cities around the world were significantly higher than those of northern provinces for both seasons. The average cancer risks observed at nine administrative provinces were 8.525 x 10(-4) +/- 3.493 x 10(-3) and 2.558 x 10(-3) +/- 6.986 x 10(-3) for ingestion rate of 50 and 100 mg day(-1), respectively. The excess cancer risks of world cities for ingestion rate of 50 and 100 mg day-1 were much higher than those of Northern Thailand for 851 and 567 times in that order. Dust ingestion was exceedingly critical to non-dietary PAH exposure in comparison with PM2.5 inhalation. These results are in good agreement with those of previous studies, underlining the significance of indoor air quality on long-term adverse respiratory diseases in Asian cities.
C1 [Pongpiachan, Siwatt] NIDA, NIDA Ctr Res & Dev Disaster Prevent & Management, Sch Social & Environm Dev, Bangkok 10240, Thailand.
RP Pongpiachan, S (reprint author), NIDA, NIDA Ctr Res & Dev Disaster Prevent & Management, Sch Social & Environm Dev, Bangkok 10240, Thailand.
EM pongpiajun@gmail.com
FU National Institute of Development Administration (NIDA) Research Center
FX This project was financed by National Institute of Development
Administration (NIDA) Research Center. The author acknowledges Assist.
Prof. Dr. Torpong Kreetachart from School of Energy and Environment
(SEEN), University of Phayao for their contributions on laboratory
works. The authors thank the kind support from Pollution Control
Department, Ministry of Natural Resources and Environment for providing
meteorological data.
NR 79
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Z9 4
U1 8
U2 8
PU TAIWAN ASSOC AEROSOL RES-TAAR
PI TAICHUNG COUNTY
PA CHAOYANG UNIV TECH, DEPT ENV ENG & MGMT, PROD CTR AAQR, NO 168, JIFONG E
RD, WUFONG TOWNSHIP, TAICHUNG COUNTY, 41349, TAIWAN
SN 1680-8584
EI 2071-1409
J9 AEROSOL AIR QUAL RES
JI Aerosol Air Qual. Res.
PD NOV
PY 2016
VL 16
IS 11
SI SI
BP 2907
EP 2919
DI 10.4209/aaqr.2015.01.0011
PG 13
WC Environmental Sciences
SC Environmental Sciences & Ecology
GA EI2HI
UT WOS:000392307100025
ER
PT J
AU Roberts, L
Ratnapriya, R
du Plessis, M
Chaitankar, V
Ramesar, RS
Swaroop, A
AF Roberts, Lisa
Ratnapriya, Rinki
du Plessis, Morne
Chaitankar, Vijender
Ramesar, Raj S.
Swaroop, Anand
TI Molecular Diagnosis of Inherited Retinal Diseases in Indigenous African
Populations by Whole-Exome Sequencing
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
DE next generation sequencing; genetic testing; photoreceptor dysfunction;
South Africa; vision loss; inherited blindness; retinal degeneration;
clinical genetics
ID RETINITIS-PIGMENTOSA; SOUTHERN AFRICA; MUTATIONS; GENE; REVEALS;
DISCOVERY; VARIANTS; DYSTROPHY; FRAMEWORK; FAMILIES
AB PURPOSE. A majority of genes associated with inherited retinal diseases (IRDs) have been identified in patients of European origin. Indigenous African populations exhibit rich genomic diversity, and evaluation of reported genetic mutations has yielded low returns so far. Our goal was to perform whole-exome sequencing (WES) to examine variants in known IRD genes in underrepresented African cohorts.
METHODS. Whole-exome sequencing was performed on 56 samples from 16 families with diverse IRD phenotypes that had remained undiagnosed after screening for known mutations using genotyping-based microarrays (Asper Ophthalmics). Variants in reported IRD genes were identified using WES and validated by Sanger sequencing. Custom TaqMan assays were used to screen for identified mutations in 193 unrelated indigenous Africans with IRDs.
RESULTS. A total of 3494 variants were identified in 217 known IRD genes, leading to the identification of seven different mutations (including six novel) in six genes (RHO, PRPF3, PRPF31, ABCA4, CERKL, and PDE6B) in six distinct families. TaqMan screening in additional probands revealed identical homozygous CERKL and PDE6B variants in four more patients.
CONCLUSIONS. This is the first report of WES of patients with IRDs in indigenous African populations. Our study identified genetic defects in almost 40% of the families analyzed, significantly enhancing the molecular diagnosis of IRD in South Africa. Thus, WES of understudied cohorts seems to present an effective strategy for determining novel mutations in heterogeneous retinal diseases.
C1 [Roberts, Lisa; du Plessis, Morne; Ramesar, Raj S.] Univ Cape Town, MRC Human Genet Res Unit, Inst Infect Dis & Mol Med IDM, Div Human Genet,Dept Pathol,Fac Hlth Sci, Cape Town, Western Cape, South Africa.
[Ratnapriya, Rinki; Chaitankar, Vijender; Swaroop, Anand] NEI, Neurobiol Neurodegenerat & Repair Lab, MSC0610,6 Ctr St, Bethesda, MD 20892 USA.
RP Swaroop, A (reprint author), NEI, Neurobiol Neurodegenerat & Repair Lab, MSC0610,6 Ctr St, Bethesda, MD 20892 USA.; Roberts, L (reprint author), Univ Cape Town, Inst Infect Dis & Mol Med, Fac Hlth Sci, N3-14,Level 3,Wernher & Beit North Bldg,Anzio Rd, ZA-7925 Cape Town, Western Cape, South Africa.
EM lisa.roberts@uct.ac.za; swaroopa@nei.nih.gov
FU Retina South Africa; Medical Research Council of South Africa;
Intramural Research Program of the National Eye Institute [EY000546]
FX Research in South Africa was funded by Retina South Africa and the
Medical Research Council of South Africa. WES and data analysis were
supported by the Intramural Research Program (EY000546) of the National
Eye Institute and utilized computational resources of the National
Institutes of Health High-Performance Computing Biowulf cluster
(https://hpc.nih.gov).
NR 52
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Z9 0
U1 1
U2 1
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
EI 1552-5783
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD NOV
PY 2016
VL 57
IS 14
BP 6374
EP 6381
DI 10.1167/iovs.16-19785
PG 8
WC Ophthalmology
SC Ophthalmology
GA EI3HG
UT WOS:000392380000063
PM 27898983
ER
PT J
AU Datiles, MB
Hejtmancik, JF
AF Datiles, Manuel B.
Hejtmancik, J. Fielding
TI Congenital Cataracts: Classification and Association With Anterior
Segment Abnormalities
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Editorial Material
C1 [Datiles, Manuel B.; Hejtmancik, J. Fielding] NEI, NIH, Bethesda, MD 20892 USA.
RP Datiles, MB (reprint author), NEI, NIH, Bethesda, MD 20892 USA.
EM datilesm@nei.nih.gov
NR 6
TC 0
Z9 0
U1 0
U2 0
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
EI 1552-5783
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD NOV
PY 2016
VL 57
IS 14
BP 6396
EP 6396
DI 10.1167/iovs.16-21074
PG 1
WC Ophthalmology
SC Ophthalmology
GA EI3HG
UT WOS:000392380000066
PM 27898986
ER
PT J
AU Kosty, MP
Hanley, A
Chollette, V
Bruinooge, SS
Taplin, SH
AF Kosty, Michael P.
Hanley, Amy
Chollette, Veronica
Bruinooge, Suanna S.
Taplin, Steven H.
TI National Cancer Institute-American Society of Clinical Oncology Teams in
Cancer Care Project
SO JOURNAL OF ONCOLOGY PRACTICE
LA English
DT Editorial Material
ID JOB-SATISFACTION
C1 [Kosty, Michael P.] Scripps Clin, 10666 N Torrey Pines Rd,MS 217, La Jolla, CA 92037 USA.
Amer Soc Clin Oncol, Alexandria, VA USA.
NCI, Bethesda, MD 20892 USA.
RP Kosty, MP (reprint author), Scripps Clin, 10666 N Torrey Pines Rd,MS 217, La Jolla, CA 92037 USA.
EM mkosty@scripps.edu
FU Conquer Cancer Foundation Mission Endowment
FX The production of this manuscript was funded by the Conquer Cancer
Foundation Mission Endowment. We wish to acknowledge the team that made
this project a success. A special thank you to the group of patient
advocates who kept the process focused on the patient and shared their
experiences as patients and caregivers. In addition to the authors, we
thank Eduardo Salas, PhD (Rice University), Sallie Weaver, PhD, MHS
(Johns Hopkins University School of Medicine), Amanda Vogel, PhD, MPH
(National Cancer Institute [NCI]), Brad Hesse, PhD(NCI), and Roni
Reiter-Palmon, PhD(University of Nebraska Omaha), for their thoughtful
insights and commentary; Caroline Schenkel (ASCO) and Mary May Kozlik
(ASCO) for administrative support; reviewers who devoted significant
time to evaluate applications and provided valuable feedback on draft
manuscripts; the membership of the ASCO Workforce Advisory Group, who
guided the project from its inception to the publication of these
papers; and the23 teams who participated in this project. A list of
those who participated in the February workshop and provided feedback on
the draft papers is below. Jacqui Adams, MD, PhD; Noel Arring, DNP, RN,
OCN; Bijal Balasubramanian, MD, PhD; Dena Battle; Rebecca Block, PhD,
MSW, LCSW; Katherine L. Byar, MSN, APN, BC, BMTCN; Beverly Canin; Julia
Lee Close, MD; Hannah Klein Connolly, MA; Robert Cooper, MD; John Cox,
DO, FASCO; Sarah D'Ambruoso, NP; Susan (Soosi) Day, PhD; Dusty Joy
Donaldson, MA; Amy Driga, OTR, BScOT; TeMaya Eatmon; Lee Ellington, PhD;
Iris C. Fineberg, PhD, MSW, OSW-C; David Gerber, MD; Tracy Gosselin,
PhD, MSN; Deborah Diaz Granados, PhD; Lisa Greaves; Anne H. Gross, PhD,
RN, FAAN; Lauren Hamel, PhD; Elizabeth Henry, MD; Dawn Hershman, MD, MS;
Brad Hesse, PhD; Maribeth Hohenstein, RN, BSN; Rosa Holloway; Fleur
Huang, MD, MPH; Anshu Jain, MD; Rebecca Johnson, MD; Joann Keyton, PhD;
Nandita Khera, MD; Michael A. King, MHA; Elizabeth Lazzara, PhD; Lynne
Lederman, PhD; Ryan Leib; Rebecca Lobb, ScD, MPH; Filipa Lynce, MD;
Catherine Fiona Macpherson, PhD, RN; Debra L. Madden, BA; Larissa A.
Meyer, MD, MPH; Burt Needles, MD; Ingrid M. Nembhard, PhD, MS; Phioanh
Leia Nghiemphu, MD; Katia Noyes, PhD, MPH; Sharon Nyquist; Susan K.
Parsons, MD; Todd Pickard, MMSc, PA-C; Diane Portman, MD; Ryan
Ramaekers, MD; Roni Reiter-Palmon, PhD; Gladys Rodriguez, MD; Hector P.
Rodriguez, PhD, MPH; Carole Seigel; Ayan Sen, MD, MSc, FAAEM, FAC; Nick
Sevdalis, PhD; Jon Tilburt, MD; Manasi A. Tirodkar, MS, PhD; Anne Ramey
Tonachel; Richard Tonachel; Dominique Tremblay; Julia Trosman, PhD, MBA;
Shin-Ping Tu, MD, MPH, FACP; Amanda Vogel, PhD, MPH; Julie Vose, MD,
MBA, FASCO; Julie Waldfogel, PharmD, CPE; Anne Walling, MD, PhD; Sallie
Weaver, PhD; Christine B. Weldon, MBA; Erin Williams, BA, MBA; Stephanie
F. Williams, MD; and Yu-NingWong, MD, MSCE.
NR 14
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U2 1
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 1554-7477
EI 1935-469X
J9 J ONCOL PRACT
JI J. Oncol. Pract.
PD NOV
PY 2016
VL 12
IS 11
BP 955
EP +
DI 10.1200/JOP.2016.018127
PG 5
WC Health Care Sciences & Services
SC Health Care Sciences & Services
GA EI3HS
UT WOS:000392381400001
PM 27756798
ER
PT J
AU Vogel, AL
Hall, KL
AF Vogel, Amanda L.
Hall, Kara L.
TI Creating the Conditions for Implementing Team Principles in Cancer Care
SO JOURNAL OF ONCOLOGY PRACTICE
LA English
DT Editorial Material
C1 Leidos Biomed Res, Clin Monitoring Res Program, Frederick, MD USA.
NCI, Bethesda, MD 20892 USA.
RP Vogel, AL (reprint author), Leidos Biomed Res Inc, Clin Res Directorate, Clin Monitoring Res Program, 9609 Med Ctr Dr,Room 3W-270, Rockville, MD 20850 USA.
EM Amanda.Vogel@fnlcr.nih.gov
FU National Cancer Institute, National Institutes of Health
[HHSN261200800001E]; Conquer Cancer Foundation Mission Endowment
FX This project has been funded in whole or in part with funds from the
National Cancer Institute, National Institutes of Health, under Contract
No. HHSN261200800001E. The production of this manuscript was funded by
the Conquer Cancer Foundation Mission Endowment. 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. The opinions expressed here are those of the authors and
cannot be construed to reflect the views of the National Cancer
Institute or the US Federal Government. We thank Tracey Goldner of the
Behavioral Research Program, Division of Cancer Control and Population
Sciences, National Cancer Institute, for her help with graphic design.
NR 15
TC 0
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U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 1554-7477
EI 1935-469X
J9 J ONCOL PRACT
JI J. Oncol. Pract.
PD NOV
PY 2016
VL 12
IS 11
BP 964
EP +
DI 10.1200/JOP.2016.018218
PG 7
WC Health Care Sciences & Services
SC Health Care Sciences & Services
GA EI3HS
UT WOS:000392381400002
PM 27858545
ER
PT J
AU Johnson, RH
Macpherson, CF
Smith, AW
Block, RG
Keyton, J
AF Johnson, Rebecca H.
Macpherson, Catherine Fiona
Smith, Ashley W.
Block, Rebecca G.
Keyton, Joann
TI Facilitating Teamwork in Adolescent and Young Adult Oncology
SO JOURNAL OF ONCOLOGY PRACTICE
LA English
DT Article
ID CANCER; CARE; HEALTH; BEHAVIORS; EMERGENCY; SURVIVORS; TEAMS; MODEL
AB A case of a young adult patient in the days immediately after a cancer diagnosis illustrates the critical importance of three interrelated core coordinating mechanisms-closed-loop communication, shared mental models, and mutual trust-of teamwork in an adolescent and young adult multidisciplinary oncology team. The case illustrates both the opportunities to increase team member coordination and the problems that can occur when coordination breaks down. A model for teamwork is presented, which highlights the relationships among these coordinating mechanisms and demonstrates how balance among them works to optimize team function and patient care. Implications for clinical practice and research suggested by the case are presented.
C1 MultiCare Hlth Syst, Mary Bridge Hosp, Tacoma, WA USA.
Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA.
NCI, Bethesda, MD 20892 USA.
Crit Mass Young Adult Canc Alliance, Austin, TX USA.
North Carolina State Univ, Raleigh, NC USA.
RP Johnson, RH (reprint author), POB 5299,311 S L St, Tacoma, WA 98415 USA.
EM beckyj100@gmail.com
FU Amgen (Inst)
FX Amgen (Inst)
NR 47
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U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 1554-7477
EI 1935-469X
J9 J ONCOL PRACT
JI J. Oncol. Pract.
PD NOV
PY 2016
VL 12
IS 11
BP 1067
EP +
DI 10.1200/JOP.2016.013870
PG 11
WC Health Care Sciences & Services
SC Health Care Sciences & Services
GA EI3HS
UT WOS:000392381400016
PM 27624944
ER
PT J
AU Jelsema, CM
Peddada, SD
AF Jelsema, Casey M.
Peddada, Shyamal D.
TI CLME: An R Package for Linear Mixed Effects Models under Inequality
Constraints
SO JOURNAL OF STATISTICAL SOFTWARE
LA English
DT Article
DE distribution free; linear inequality constraints; linear fixed effects
models; linear mixed effects models; order restricted inference;
residual bootstrap; R
ID LONGITUDINAL DATA; DOSE-RESPONSE; HEARING-LOSS; INFERENCE
AB In many applications researchers are typically interested in testing for inequality constraints in the context of linear fixed effects and mixed effects models. Although there exists a large body of literature for performing statistical inference under inequality constraints, user friendly statistical software implementing such methods is lacking, especially in the context of linear fixed and mixed effects models. In this article we introduce CLME, a package in the R language that can be used for testing a broad collection of inequality constraints. It uses residual bootstrap based methodology which is reasonably robust to non-normality as well as heteroscedasticity. The package is illustrated using two data sets. The package also contains a graphical user interface built using the shiny package.
C1 [Jelsema, Casey M.] West Virginia Univ, Dept Stat, Morgantown, WV 26506 USA.
[Peddada, Shyamal D.] NIEHS, Biostat & Computat Biol Branch, 111 TW Alexander Dr, Res Triangle Pk, NC USA.
RP Jelsema, CM (reprint author), West Virginia Univ, Dept Stat, Morgantown, WV 26506 USA.
EM casey.jelsema@mail.wvu.edu; peddada@niehs.nih.gov
FU Intramural Research Program of the NIH, NIEHS [Z01 ES101744]
FX This research is supported (in part) by the Intramural Research Program
of the NIH, NIEHS (Z01 ES101744). The authors thank the following
individuals: Drs. Katie O'Brien, Keith Shockley, and Bahjat Qaqish for
carefully reading the manuscript and making numerous suggestions which
substantially improved the presentation; Dr. Michelle Cora for providing
the data on Sprague-Dawley rats analyzed in Section 4.1; and the editors
of the Journal of Statistical Software and the two anonymous reviewers
for providing suggestions which improved this work.
NR 24
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U1 0
U2 0
PU JOURNAL STATISTICAL SOFTWARE
PI LOS ANGELES
PA UCLA DEPT STATISTICS, 8130 MATH SCIENCES BLDG, BOX 951554, LOS ANGELES,
CA 90095-1554 USA
SN 1548-7660
J9 J STAT SOFTW
JI J. Stat. Softw.
PD NOV
PY 2016
VL 75
IS 1
DI 10.18637/jss.v075.i01
PG 32
WC Computer Science, Interdisciplinary Applications; Statistics &
Probability
SC Computer Science; Mathematics
GA EI7SO
UT WOS:000392703800001
ER
PT J
AU Ahi, YS
Zhang, S
Thappeta, Y
Denman, A
Feizpour, A
Gummuluru, S
Reinhard, B
Muriaux, D
Fivash, MJ
Rein, A
AF Ahi, Yadvinder S.
Zhang, Shu
Thappeta, Yashna
Denman, Audrey
Feizpour, Amin
Gummuluru, Suryaram
Reinhard, Bjoern
Muriaux, Delphine
Fivash, Matthew J.
Rein, Alan
TI Functional Interplay Between Murine Leukemia Virus Glycogag, Serinc5,
and Surface Glycoprotein Governs Virus Entry, with Opposite Effects on
Gammaretroviral and Ebolavirus Glycoproteins
SO MBIO
LA English
DT Article
ID GLYCOSYLATED GAG PROTEIN; ENVELOPE GLYCOPROTEIN; REVERSE-TRANSCRIPTASE;
UNGLYCOSYLATED GAG; HIV-1 INFECTIVITY; CRE RECOMBINASE; T-LYMPHOCYTES;
MOUSE CELLS; RECEPTOR; GENE
AB Gammaretroviruses, such as murine leukemia viruses (MLVs), encode, in addition to the canonical Gag, Pol, and Env proteins that will form progeny virus particles, a protein called "glycogag" (glycosylated Gag). MLV glycogag contains the entire Gag sequence plus an 88-residue N-terminal extension. It has recently been reported that glycogag, like the Nef protein of HIV-1, counteracts the antiviral effects of the cellular protein Serinc5. We have found, in agreement with prior work, that glycogag strongly enhances the infectivity of MLVs with some Env proteins but not those with others. In contrast, however, glycogag was detrimental to MLVs carrying Ebolavirus glycoprotein. Glycogag could be replaced, with respect to viral infectivity, by the unrelated S2 protein of equine infectious anemia virus. We devised an assay for viral entry in which virus particles deliver the Cre recombinase into cells, leading to the expression of a reporter. Data from this assay showed that both the positive and the negative effects of glycogag and S2 upon MLV infectivity are exerted at the level of virus entry. Moreover, transfection of the virus-producing cells with a Serinc5 expression plasmid reduced the infectivity and entry capability of MLV carrying xenotropic MLV Env, particularly in the absence of glycogag. Conversely, Serinc5 expression abrogated the negative effects of glycogag upon the infectivity and entry capability of MLV carrying Ebolavirus glycoprotein. As Serinc5 may influence cellular phospholipid metabolism, it seems possible that all of these effects on virus entry derive from changes in the lipid composition of viral membranes.
IMPORTANCE Many murine leukemia viruses (MLVs) encode a protein called "glycogag." The function of glycogag is not fully understood, but it can assist HIV-1 replication in the absence of the HIV-1 protein Nef under some circumstances. In turn, Nef counteracts the cellular protein Serinc5. Glycogag enhances the infectivity of MLVs with some but not all MLV Env proteins (which mediate viral entry into the host cell upon binding to cell surface receptors). We now report that glycogag acts by enhancing viral entry and that, like Nef, glycogag antagonizes Serinc5. Surprisingly, the effects of glycogag and Serinc5 upon the entry and infectivity of MLV particles carrying an Ebolavirus glycoprotein are the opposite of those observed with the MLV Env proteins. The unrelated S2 protein of equine infectious anemia virus (EIAV) is functionally analogous to glycogag in our experiments. Thus, three retroviruses (HIV-1, MLV, and EIAV) have independently evolved accessory proteins that counteract Serinc5.
C1 [Ahi, Yadvinder S.; Zhang, Shu; Thappeta, Yashna; Denman, Audrey; Rein, Alan] NCI, HIV Dynam & Replicat Program, Frederick, MD 21701 USA.
[Feizpour, Amin; Reinhard, Bjoern] Boston Univ, Dept Chem, 590 Commonwealth Ave, Boston, MA 02215 USA.
[Feizpour, Amin; Reinhard, Bjoern] Boston Univ, Photon Ctr, Boston, MA 02215 USA.
[Gummuluru, Suryaram] Boston Univ, Sch Med, Dept Microbiol, Boston, MA 02118 USA.
[Muriaux, Delphine] CNRS, UMR 5236, Ctr Etud Agents & Pathogenes & Biotechnol Santes, Montpellier, France.
[Fivash, Matthew J.] Natl Canc Inst Frederick, Data Management Serv, Frederick, MD USA.
RP Rein, A (reprint author), NCI, HIV Dynam & Replicat Program, Frederick, MD 21701 USA.
EM reina@mail.nih.gov
FU CNRS; HHS | NIH | National Cancer Institute (NCI); HHS | NIH | National
Institute of Allergy and Infectious Diseases (NIAID) [AI064099]
FX This work, including the efforts of Delphine Muriaux, was funded by
CNRS. This work, including the efforts of Yadvinder S. Ahi, Shu Zhang,
Yashna Thappeta, Audrey Denman, Matthew Fivash, and Alan Rein, was
funded by HHS | NIH | National Cancer Institute (NCI). This work,
including the efforts of Amin Feizpour, Suryaram Gummuluru, and Bjoern
Reinhard, was funded by HHS | NIH | National Institute of Allergy and
Infectious Diseases (NIAID) (AI064099).
NR 71
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U1 0
U2 0
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 2150-7511
J9 MBIO
JI mBio
PD NOV-DEC
PY 2016
VL 7
IS 6
AR e01985
DI 10.1128/mBio.01985-16
PG 14
WC Microbiology
SC Microbiology
GA EH9GK
UT WOS:000392079500043
ER
PT J
AU Bansal, A
Ojo, KK
Mu, J
Maly, DJ
Van Voorhis, WC
Miller, LH
AF Bansal, Abhisheka
Ojo, Kayode K.
Mu, Jianbing
Maly, Dustin J.
Van Voorhis, Wesley C.
Miller, Louis H.
TI Reduced Activity of Mutant Calcium-Dependent Protein Kinase 1 Is
Compensated in Plasmodium falciparum through the Action of Protein
Kinase G
SO MBIO
LA English
DT Article
ID MALARIA PARASITES; INHIBITORS; TOXOPLASMA; TRANSMISSION; TARGETS;
POCKET; POTENT; IDENTIFICATION; ACTIVATION; EXPRESSION
AB We used a sensitization approach that involves replacement of the gatekeeper residue in a protein kinase with one with a different side chain. The activity of the enzyme with a bulky gatekeeper residue, such as methionine, cannot be inhibited using bumped kinase inhibitors (BKIs). Here, we have used this approach to study Plasmodium falciparum calcium-dependent protein kinase 1 (PfCDPK1). The methionine gatekeeper substitution, T145M, although it led to a 47% reduction in transphosphorylation, was successfully introduced into the CDPK1 locus using clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9. As methionine is a bulky residue, BKI 1294 had a 10-fold-greater effect in vitro on the wild-type enzyme than on the methionine mutant. However, in contrast to in vitro data with recombinant enzymes, BKI 1294 had a slightly greater inhibition of the growth of CDPK1 T145M parasites than the wild type. Moreover, the CDPK1 T145M parasites were more sensitive to the action of compound 2 (C2), a specific inhibitor of protein kinase G (PKG). These results suggest that a reduction in the activity of CDPK1 due to methionine substitution at the gatekeeper position is compensated through the direct action of PKG or of another kinase under the regulation of PKG. The transcript levels of CDPK5 and CDPK6 were significantly upregulated in the CDPK1 T145M parasites. The increase in CDPK6 or some other kinase may compensate for decrease in CDPK1 activity during invasion. This study suggests that targeting two kinases may be more effective in chemotherapy to treat malaria so as not to select for mutations in one of the enzymes.
IMPORTANCE Protein kinases of Plasmodium falciparum are being actively pursued as drug targets to treat malaria. However, compensatory mechanisms may reverse the drug activity against a kinase. In this study, we show that replacement of the wildtype threonine gatekeeper residue with methionine reduces the transphosphorylation activity of CDPK1. Mutant parasites with methionine gatekeeper residue compensate the reduced activity of CDPK1 through the action of PKG possibly by upregulation of CDPK6 or some other kinase. This study highlights that targeting one enzyme may lead to changes in transcript expression of other kinases that compensate for its function and may select for mutants that are less dependent on the target enzyme activity. Thus, inhibiting two kinases is a better strategy to protect the antimalarial activity of each, similar to artemisinin combination therapy or malarone (atovaquone and proguanil).
C1 [Bansal, Abhisheka; Mu, Jianbing; Miller, Louis H.] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA.
[Ojo, Kayode K.; Van Voorhis, Wesley C.] Univ Washington, Dept Med, Div Allergy & Infect Dis, Seattle, WA USA.
[Ojo, Kayode K.; Van Voorhis, Wesley C.] Univ Washington, Ctr Emerging & Re Emerging Infect Dis, Seattle, WA 98195 USA.
[Maly, Dustin J.] Univ Washington, Dept Biochem, Seattle, WA 98195 USA.
[Maly, Dustin J.] Univ Washington, Dept Chem, Seattle, WA 98195 USA.
RP Bansal, A; Miller, LH (reprint author), NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA.
EM bansal.abhisheka@gmail.com; LMILLER@niaid.nih.gov
FU HHS | NIH | National Institute of Allergy and Infectious Diseases
(NIAID) [R01 AI111341-01 R01AI089441-01]; HHS | NIH | Eunice Kennedy
Shriver National Institute of Child Health and Human Development (NICHD)
[R01HD080670]; United States Department of Agriculture (USDA)
[2014-06183]
FX This work, including the efforts of Wesley C. Van Voorhis, was funded by
HHS | NIH | National Institute of Allergy and Infectious Diseases
(NIAID) (R01 AI111341-01 R01AI089441-01). This work, including the
efforts of Wesley C. Van Voorhis, was funded by HHS | NIH | Eunice
Kennedy Shriver National Institute of Child Health and Human Development
(NICHD) (R01HD080670). This work, including the efforts of Wesley C. Van
Voorhis, was funded by United States Department of Agriculture (USDA)
(grant number no. 2014-06183).
NR 44
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Z9 0
U1 3
U2 3
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 2150-7511
J9 MBIO
JI mBio
PD NOV-DEC
PY 2016
VL 7
IS 6
AR e02011
DI 10.1128/mBio.02011-16
PG 12
WC Microbiology
SC Microbiology
GA EH9GK
UT WOS:000392079500057
ER
PT J
AU Bennuru, S
Cotton, JA
Ribeiro, JMC
Grote, A
Harsha, B
Holroyd, N
Mhashilkar, A
Molina, DM
Randall, AZ
Shandling, AD
Unnasch, TR
Ghedin, E
Berriman, M
Lustigman, S
Nutman, TB
AF Bennuru, Sasisekhar
Cotton, James A.
Ribeiro, Jose M. C.
Grote, Alexandra
Harsha, Bhavana
Holroyd, Nancy
Mhashilkar, Amruta
Molina, Douglas M.
Randall, Arlo Z.
Shandling, Adam D.
Unnasch, Thomas R.
Ghedin, Elodie
Berriman, Matthew
Lustigman, Sara
Nutman, Thomas B.
TI Stage-Specific Transcriptome and Proteome Analyses of the Filarial
Parasite Onchocerca volvulus and Its Wolbachia Endosymbiont
SO MBIO
LA English
DT Article
ID PUTATIVELY IMMUNE INDIVIDUALS; NEGLECTED TROPICAL DISEASES;
BRUGIA-MALAYI; CAENORHABDITIS-ELEGANS; RNA INTERFERENCE;
GENE-EXPRESSION; CATHEPSIN-L; NEMATODE; LARVAL; IDENTIFICATION
AB Onchocerciasis (river blindness) is a neglected tropical disease that has been successfully targeted by mass drug treatment programs in the Americas and small parts of Africa. Achieving the long-term goal of elimination of onchocerciasis, however, requires additional tools, including drugs, vaccines, and biomarkers of infection. Here, we describe the transcriptome and proteome profiles of the major vector and the human host stages (L1, L2, L3, molting L3, L4, adult male, and adult female) of Onchocerca volvulus along with the proteome of each parasitic stage and of its Wolbachia endosymbiont (wOv). In so doing, we have identified stage-specific pathways important to the parasite's adaptation to its human host during its early development. Further, we generated a protein array that, when screened with well-characterized human samples, identified novel diagnostic biomarkers of O. volvulus infection and new potential vaccine candidates. This immunomic approach not only demonstrates the power of this postgenomic discovery platform but also provides additional tools for onchocerciasis control programs.
IMPORTANCE The global onchocerciasis (river blindness) elimination program will have to rely on the development of new tools (drugs, vaccines, biomarkers) to achieve its goals by 2025. As an adjunct to the completed genomic sequencing of O. volvulus, we used a comprehensive proteomic and transcriptomic profiling strategy to gain a comprehensive understanding of both the vector-derived and human host-derived parasite stages. In so doing, we have identified proteins and pathways that enable novel drug targeting studies and the discovery of novel vaccine candidates, as well as useful biomarkers of active infection.
C1 [Bennuru, Sasisekhar; Nutman, Thomas B.] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
[Cotton, James A.; Harsha, Bhavana; Holroyd, Nancy; Berriman, Matthew] Wellcome Trust Sanger Inst, Wellcome Genome Campus, Hinxton, Cambs, England.
[Ribeiro, Jose M. C.] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD USA.
[Grote, Alexandra; Ghedin, Elodie] NYU, Dept Biol, Ctr Genom & Syst Biol, New York, NY 10003 USA.
[Mhashilkar, Amruta; Unnasch, Thomas R.] Univ S Florida, Tampa, FL USA.
[Molina, Douglas M.; Randall, Arlo Z.; Shandling, Adam D.] Antigen Discovery Inc, Irvine, CA USA.
[Ghedin, Elodie] NYU, Coll Global Publ Hlth, New York, NY USA.
[Lustigman, Sara] New York Blood Ctr, New York, NY 10021 USA.
RP Nutman, TB (reprint author), NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.; Lustigman, S (reprint author), New York Blood Ctr, New York, NY 10021 USA.
EM slustigman@nybloodcenter.org; tnutman@niaid.nih.gov
OI Ribeiro, Jose/0000-0002-9107-0818
FU Division of Intramural Research, National Institute of Allergy and
Infectious Diseases (DIR, NIAID) [1ZIAAI000512]; Bill and Melinda Gates
Foundation (Bill & Melinda Gates Foundation); HHS | NIH | National
Institute of Allergy and Infectious Diseases (NIAID) [AI126466,
AI42328]; Wellcome Trust through Wellcome Trust Sanger Institute
[098051]; New York Blood Center; Edna McConnell Clark Foundation
FX This work, including the efforts of Sasisekhar Bennuru, Jose M. C.
Ribeiro, and Thomas B. Nutman, was funded by Division of Intramural
Research, National Institute of Allergy and Infectious Diseases (DIR,
NIAID) (1ZIAAI000512). This work, including the efforts of Sasisekhar
Bennuru, Jose M. C. Ribeiro, Sara Lustigman, and Thomas B. Nutman, was
funded by Bill and Melinda Gates Foundation (Bill & Melinda Gates
Foundation). This work, including the efforts of Elodie Ghedin and
Alexandra Grote, was funded by in part by HHS | NIH | National Institute
of Allergy and Infectious Diseases (NIAID) (AI126466). This work,
including the efforts of James A. Cotton, Bhavana Harsha, Nancy Holroyd,
and Matthew Berriman, was funded by the Wellcome Trust through core
funding of the Wellcome Trust Sanger Institute (098051).; This work,
including the efforts of Sara Lustigman, was funded in part from the New
York Blood Center, The Edna McConnell Clark Foundation, and by HHS | NIH
| National Institute of Allergy and Infectious Diseases (NIAID)
(AI42328).
NR 65
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U1 0
U2 0
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 2150-7511
J9 MBIO
JI mBio
PD NOV-DEC
PY 2016
VL 7
IS 6
AR e02028
DI 10.1128/mBio.02028-16
PG 11
WC Microbiology
SC Microbiology
GA EH9GK
UT WOS:000392079500045
ER
PT J
AU Chu, CY
Stewart, PE
Bestor, A
Hansen, B
Lin, T
Gao, LH
Norris, SJ
Rosa, PA
AF Chu, Chen-Yi
Stewart, Philip E.
Bestor, Aaron
Hansen, Bryan
Lin, Tao
Gao, Lihui
Norris, Steven J.
Rosa, Patricia A.
TI Function of the Borrelia burgdorferi FtsH Homolog Is Essential for
Viability both In Vitro and In Vivo and Independent of HflK/C (vol 7,
e00404-16, 2016)
SO MBIO
LA English
DT Correction
C1 [Chu, Chen-Yi; Stewart, Philip E.; Bestor, Aaron; Rosa, Patricia A.] NIAID, Lab Zoonot Pathogens, NIH, Hamilton, MT 59840 USA.
[Hansen, Bryan] NIAID, Res Technol Branch, Rocky Mt Labs, NIH, Hamilton, MT USA.
[Lin, Tao; Gao, Lihui; Norris, Steven J.] UTHealth, McGovern Med Sch, Dept Pathol & Lab Med, Houston, TX USA.
[Chu, Chen-Yi] Acad Mil Med Sci, Inst Dis Control & Prevent, Beijing, Peoples R China.
RP Stewart, PE (reprint author), NIAID, Lab Zoonot Pathogens, NIH, Hamilton, MT 59840 USA.
EM pestewart@niaid.nih.gov
NR 1
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Z9 0
U1 0
U2 0
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 2150-7511
J9 MBIO
JI mBio
PD NOV-DEC
PY 2016
VL 7
IS 6
AR e02135-16
DI 10.1128/mBio.02135-16
PG 1
WC Microbiology
SC Microbiology
GA EH9GK
UT WOS:000392079500075
ER
PT J
AU He, SS
Chandler, M
Varani, AM
Hickman, AB
Dekker, JP
Dyda, F
AF He, Susu
Chandler, Michael
Varani, Alessandro M.
Hickman, Alison B.
Dekker, John P.
Dyda, Fred
TI Mechanisms of Evolution in High-Consequence Drug Resistance Plasmids
SO MBIO
LA English
DT Article
ID INSERTION SEQUENCES; TARGET IMMUNITY; BACTERIOPHAGE MU; B-PROTEIN;
TRANSPOSITION; RECOMBINATION; IDENTIFICATION; REPLICATION; DELETIONS;
TN7
AB The dissemination of resistance among bacteria has been facilitated by the fact that resistance genes are usually located on a diverse and evolving set of transmissible plasmids. However, the mechanisms generating diversity and enabling adaptation within highly successful resistance plasmids have remained obscure, despite their profound clinical significance. To understand these mechanisms, we have performed a detailed analysis of the mobilome (the entire mobile genetic element content) of a set of previously sequenced carbapenemase-producing Enterobacteriaceae (CPE) from the National Institutes of Health Clinical Center. This analysis revealed that plasmid reorganizations occurring in the natural context of colonization of human hosts were overwhelmingly driven by genetic rearrangements carried out by replicative transposons working in concert with the process of homologous recombination. A more complete understanding of the molecular mechanisms and evolutionary forces driving rearrangements in resistance plasmids may lead to fundamentally new strategies to address the problem of antibiotic resistance.
IMPORTANCE The spread of antibiotic resistance among Gram-negative bacteria is a serious public health threat, as it can critically limit the types of drugs that can be used to treat infected patients. In particular, carbapenem-resistant members of the Enterobacteriaceae family are responsible for a significant and growing burden of morbidity and mortality. Here, we report on the mechanisms underlying the evolution of several plasmids carried by previously sequenced clinical Enterobacteriaceae isolates from the National Institutes of Health Clinical Center (NIH CC). Our ability to track genetic rearrangements that occurred within resistance plasmids was dependent on accurate annotation of the mobile genetic elements within the plasmids, which was greatly aided by access to long-read DNA sequencing data and knowledge of their mechanisms. Mobile genetic elements such as transposons and integrons have been strongly associated with the rapid spread of genes responsible for antibiotic resistance. Understanding the consequences of their actions allowed us to establish unambiguous evolutionary relationships between plasmids in the analysis set.
C1 [He, Susu; Hickman, Alison B.; Dyda, Fred] NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
[Chandler, Michael] CNRS, Lab Microbiol & Genet Mol, Toulouse, France.
[Varani, Alessandro M.] Univ Estadual Paulista, Dept Tecnol, Fac Ciencias Agr & Vet Jaboticabal, Sao Paulo, Brazil.
[Dekker, John P.] NIH, Dept Lab Med, Ctr Clin, Microbiol Serv, Bldg 10, Bethesda, MD 20892 USA.
RP Dyda, F (reprint author), NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
EM fred.dyda@nih.gov
FU HHS | National Institutes of Health (NIH); Coordenacao de
Aperfeicoamento de Pessoal de Nivel Superior (CAPES); HHS | NIH | NIH
Clinical Center; Intramural Program of the National Institute of
Diabetes and Digestive and Kidney Diseases; NIH Clinical Center
FX This work, including the efforts of Alison B. Hickman, was funded by HHS
| National Institutes of Health (NIH). This work, including the efforts
of Fred Dyda, was funded by HHS | National Institutes of Health (NIH).
This work, including the efforts of Susu He, was funded by HHS |
National Institutes of Health (NIH). This work, including the efforts of
Alessandro M. Varani, was funded by Coordenacao de Aperfeicoamento de
Pessoal de Nivel Superior (CAPES). This work, including the efforts of
Michael Chandler, was funded by Centre National de la Recherche
Scientifique (CNRS). This work, including the efforts of John P. Dekker,
was funded by HHS | NIH | NIH Clinical Center.; This work was partially
supported by the Intramural Program of the National Institute of
Diabetes and Digestive and Kidney Diseases (S.H., A.B.H., and F.D.) and
the NIH Clinical Center (J.P.D.).
NR 32
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U1 5
U2 5
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 2150-7511
J9 MBIO
JI mBio
PD NOV-DEC
PY 2016
VL 7
IS 6
AR e01987
DI 10.1128/mBio.01987-16
PG 11
WC Microbiology
SC Microbiology
GA EH9GK
UT WOS:000392079500050
ER
PT J
AU Hidano, S
Randall, LM
Dawson, L
Dietrich, HK
Konradt, C
Klover, PJ
John, B
Harris, TH
Fang, Q
Turek, B
Kobayashi, T
Hennighausen, L
Beiting, DP
Koshy, AA
Hunter, CA
AF Hidano, Shinya
Randall, Louise M.
Dawson, Lucas
Dietrich, Hans K.
Konradt, Christoph
Klover, Peter J.
John, Beena
Harris, Tajie H.
Fang, Qun
Turek, Bradley
Kobayashi, Takashi
Hennighausen, Lothar
Beiting, Daniel P.
Koshy, Anita A.
Hunter, Christopher A.
TI STAT1 Signaling in Astrocytes Is Essential for Control of Infection in
the Central Nervous System
SO MBIO
LA English
DT Article
ID TOXOPLASMA-GONDII INFECTION; INDUCIBLE NITRIC-OXIDE; CHEMOKINE
GENE-EXPRESSION; CHRONIC VIRAL-INFECTION; T-CELL EXHAUSTION;
GAMMA-INTERFERON; IFN-GAMMA; TRANSGENIC MICE; DENDRITIC CELLS;
HOST-RESISTANCE
AB The local production of gamma interferon (IFN-gamma) is important to control Toxoplasma gondii in the brain, but the basis for these protective effects is not fully understood. The studies presented here reveal that the ability of IFN-gamma to inhibit parasite replication in astrocytes in vitro is dependent on signal transducer and activator of transcription 1 (STAT1) and that mice that specifically lack STAT1 in astrocytes are unable to limit parasite replication in the central nervous system (CNS). This susceptibility is associated with a loss of antimicrobial pathways and increased cyst formation in astrocytes. These results identify a critical role for astrocytes in limiting the replication of an important opportunistic pathogen.
IMPORTANCE Astrocytes are the most numerous cell type in the brain, and they are activated in response to many types of neuroinflammation, but their function in the control of CNS-specific infection is unclear. The parasite Toxoplasma gondii is one of the few clinically relevant microorganisms that naturally infects astrocytes, and the studies presented here establish that the ability of astrocytes to inhibit parasite replication is essential for the local control of this opportunistic pathogen. Together, these studies establish a key role for astrocytes as effector cells and in the coordination of many aspects of the protective immune response that operates in the brain.
C1 [Hidano, Shinya; Dawson, Lucas; Konradt, Christoph; John, Beena; Fang, Qun; Turek, Bradley; Beiting, Daniel P.; Hunter, Christopher A.] Univ Penn, Sch Vet Med, Dept Pathobiol, Philadelphia, PA 19104 USA.
[Randall, Louise M.] Univ Melbourne, Dept Med, Peter Doherty Inst, Parkville, Vic, Australia.
[Dietrich, Hans K.; Koshy, Anita A.] Univ Arizona, Dept Neurol, Dept Immunobiol, Inst BIO5, Tucson, AZ USA.
[Klover, Peter J.; Hennighausen, Lothar] NIDDK, Lab Genet & Physiol, NIH, Bethesda, MD 20892 USA.
[Harris, Tajie H.] Univ Virginia, Dept Neurosci, Ctr Brain Immunol & Glia BIG, Charlottesville, VA USA.
[Hidano, Shinya; Kobayashi, Takashi] Oita Univ, Fac Med, Dept Infect Dis Control, Oita, Japan.
RP Hunter, CA (reprint author), Univ Penn, Sch Vet Med, Dept Pathobiol, Philadelphia, PA 19104 USA.
EM chunter@vet.upenn.edu
FU Commonwealth of Pennsylvania; Fellowship from Strategic Young Researcher
Overseas Visits Program for Accelerating Brain Circulation; NIH
[AI41158, 5R21EY021314, NS65116]; Deutsche Forschungsgemeinschaft; IRP
of the NIDDK/NIH
FX This work was supported by the Commonwealth of Pennsylvania, a
Fellowship from Strategic Young Researcher Overseas Visits Program for
Accelerating Brain Circulation (S.H.), NIH grants AI41158 and
5R21EY021314 (C.A.H.), and the Deutsche Forschungsgemeinschaft (C.K.).
L.H. and P.J.K. were supported by the IRP of the NIDDK/NIH, while A.A.K.
was supported by NIH NS65116.
NR 78
TC 0
Z9 0
U1 3
U2 3
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 2150-7511
J9 MBIO
JI mBio
PD NOV-DEC
PY 2016
VL 7
IS 6
AR e01881-16
DI 10.1128/mBio.01881-16
PG 15
WC Microbiology
SC Microbiology
GA EH9GK
UT WOS:000392079500025
ER
PT J
AU Kauffman, RC
Bhuiyan, TR
Nakajima, R
Mayo-Smith, LM
Rashu, R
Hoq, MR
Chowdhury, F
Khan, AI
Rahman, A
Bhaumik, SK
Harris, L
O'Neal, JT
Trost, JF
Alam, NH
Jasinskas, A
Dotsey, E
Kelly, M
Charles, RC
Xu, P
Kovac, P
Calderwood, SB
Ryan, ET
Felgner, PL
Qadri, F
Wrammert, J
Harrise, JB
AF Kauffman, Robert C.
Bhuiyan, Taufiqur R.
Nakajima, Rie
Mayo-Smith, Leslie M.
Rashu, Rasheduzzaman
Hoq, Mohammad Rubel
Chowdhury, Fahima
Khan, Ashraful Islam
Rahman, Atiqur
Bhaumik, Siddhartha K.
Harris, Levelle
O'Neal, Justin T.
Trost, Jessica F.
Alam, Nur Haq
Jasinskas, Algis
Dotsey, Emmanuel
Kelly, Meagan
Charles, Richelle C.
Xu, Peng
Kovac, Pavol
Calderwood, Stephen B.
Ryan, Edward T.
Felgner, Phillip L.
Qadri, Firdausi
Wrammert, Jens
Harrise, Jason B.
TI Single-Cell Analysis of the Plasmablast Response to Vibrio cholerae
Demonstrates Expansion of Cross-Reactive Memory B Cells
SO MBIO
LA English
DT Article
ID HUMAN MONOCLONAL-ANTIBODIES; DENGUE VIRUS-INFECTION; O1 EL-TOR;
SALMONELLA-TYPHIMURIUM; HOUSEHOLD CONTACTS; IMMUNE-RESPONSES; TOXIN;
BANGLADESH; LIPOPOLYSACCHARIDE; DYNAMICS
AB We characterized the acute B cell response in adults with cholera by analyzing the repertoire, specificity, and functional characteristics of 138 monoclonal antibodies (MAbs) generated from single-cell-sorted plasmablasts. We found that the cholera-induced responses were characterized by high levels of somatic hypermutation and large clonal expansions. A majority of the expansions targeted cholera toxin (CT) or lipopolysaccharide (LPS). Using a novel proteomics approach, we were able to identify sialidase as another major antigen targeted by the antibody response to Vibrio cholerae infection. Antitoxin MAbs targeted both the A and B subunits, and most were also potent neutralizers of enterotoxigenic Escherichia coli heat-labile toxin. LPS-specific MAbs uniformly targeted the O-specific polysaccharide, with no detectable responses to either the core or the lipid moiety of LPS. Interestingly, the LPS-specific antibodies varied widely in serotype specificity and functional characteristics. One participant infected with the Ogawa serotype produced highly mutated LPS-specific antibodies that preferentially bound the previously circulating Inaba serotype. This demonstrates durable memory against a polysaccharide antigen presented at the mucosal surface and provides a mechanism for the long-term, partial heterotypic immunity seen following cholera.
IMPORTANCE Cholera is a diarrheal disease that results in significant mortality. While oral cholera vaccines are beneficial, they do not achieve equivalent protection compared to infection with Vibrio cholerae. Although antibodies likely mediate protection, the mechanisms of immunity following cholera are poorly understood, and a detailed understanding of antibody responses to cholera is of significance for human health. In this study, we characterized the human response to cholera at the single-plasmablast, monoclonal antibody level. Although this approach has not been widely applied to the study of human bacterial infection, we were able to uncover the basis of cross-reactivity between different V. cholerae serotypes and the likely impact of prior enterotoxigenic Escherichia coli exposure on the response to cholera, as well as identify novel antigenic targets. In addition to improving our understanding of the repertoire and function of the antibody response to cholera in humans, this study has implications for future cholera vaccination efforts.
C1 [Kauffman, Robert C.; Mayo-Smith, Leslie M.; Bhaumik, Siddhartha K.; Trost, Jessica F.; Wrammert, Jens] Emory Univ, Sch Med, Dept Pediat, Div Infect Dis, Atlanta, GA 30322 USA.
[Kauffman, Robert C.; Bhaumik, Siddhartha K.; Harris, Levelle; O'Neal, Justin T.; Trost, Jessica F.; Wrammert, Jens] Emory Univ, Sch Med, Emory Vaccine Ctr, Atlanta, GA 30322 USA.
[Bhuiyan, Taufiqur R.; Rashu, Rasheduzzaman; Hoq, Mohammad Rubel; Chowdhury, Fahima; Khan, Ashraful Islam; Rahman, Atiqur; Alam, Nur Haq; Qadri, Firdausi] Int Ctr Diarrhoeal Dis Res, Div Infect Dis, Dhaka, Bangladesh.
[Nakajima, Rie; Jasinskas, Algis; Dotsey, Emmanuel; Felgner, Phillip L.] Univ Calif Irvine, Dept Med, Irvine, CA 92717 USA.
[Rahman, Atiqur; Kelly, Meagan; Charles, Richelle C.; Calderwood, Stephen B.; Ryan, Edward T.; Harrise, Jason B.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA.
[Charles, Richelle C.; Calderwood, Stephen B.; Ryan, Edward T.] Harvard Med Sch, Dept Med, Boston, MA USA.
[Xu, Peng; Kovac, Pavol] NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA.
[Ryan, Edward T.] Harvard TH Chan Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA USA.
[Harrise, Jason B.] Harvard Med Sch, Dept Pediat, Boston, MA 02115 USA.
RP Wrammert, J (reprint author), Emory Univ, Sch Med, Dept Pediat, Div Infect Dis, Atlanta, GA 30322 USA.; Wrammert, J (reprint author), Emory Univ, Sch Med, Emory Vaccine Ctr, Atlanta, GA 30322 USA.; Harrise, JB (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA.; Harrise, JB (reprint author), Harvard Med Sch, Dept Pediat, Boston, MA 02115 USA.
EM jwramme@emory.edu; jbharris@partners.org
FU HHS | National Institutes of Health (NIH) [AI103055, AI099243, AI106878,
AI058935, AI074492, TW005572]
FX This work, including the efforts of Firdausi Qadri, Jens Wrammert, and
Jason B. Harris, was funded by HHS | National Institutes of Health (NIH)
(AI103055). This work, including the efforts of Firdausi Qadri and Jason
B. Harris, was funded by HHS | National Institutes of Health (NIH)
(AI099243). This work, including the efforts of Edward T Ryan and
Firdausi Qadri, was funded by HHS | National Institutes of Health (NIH)
(AI106878). This work, including the efforts of Edward T Ryan and
Firdausi Qadri, was funded by HHS | National Institutes of Health (NIH)
(AI058935). This work, including the efforts of Robert C. Kauffman, was
funded by HHS | National Institutes of Health (NIH) (AI074492). This
work, including the efforts of Taufiqur Bhuiyan, was funded by HHS |
National Institutes of Health (NIH) (TW005572).
NR 44
TC 0
Z9 0
U1 2
U2 2
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 2150-7511
J9 MBIO
JI mBio
PD NOV-DEC
PY 2016
VL 7
IS 6
AR e02021
DI 10.1128/mBio.02021-16
PG 11
WC Microbiology
SC Microbiology
GA EH9GK
UT WOS:000392079500066
ER
PT J
AU McKinney, CC
Kim, MJ
Chen, D
McBride, AA
AF McKinney, Caleb C.
Kim, Min Jung
Chen, Dan
McBride, Alison A.
TI Brd4 Activates Early Viral Transcription upon Human Papillomavirus 18
Infection of Primary Keratinocytes
SO MBIO
LA English
DT Article
ID BROMODOMAIN PROTEIN BRD4; E2 PROTEIN; DNA-REPLICATION; MITOTIC
CHROMOSOMES; LIFE-CYCLE; REGULATORY REGION; CHROMATIN; TYPE-16; BINDING;
PHOSPHORYLATION
AB Human papillomaviruses (HPVs) replicate in the cutaneous and mucosal epithelia, and the infectious cycle is synchronous with the differentiation program of the host keratinocytes. The virus initially infects dividing cells in the lower layers of the epithelium, where it establishes a persistent infection. The viral genome is maintained as a low-copy-number, extrachromosomal element in these proliferating cells but switches to the late stage of the life cycle in differentiated cells. The cellular chromatin adaptor protein Brd4 is involved in several stages and processes of the viral life cycle. In concert with the viral transcriptional regulator E2, Brd4 can repress transcription from the early viral promoter. Brd4 and E2 form a complex with the viral genome that associates with host chromosomes to partition the viral genome in dividing cells; Brd4 also localizes to active sites of productive HPV DNA replication. However, because of the difficulties in producing HPV viral particles, the role of Brd4 in modulating viral transcription and replication at the initial stage of infection is unclear. In this study, we have used an HPV18 quasivirus-based genome delivery system to assess the role of Brd4 in the initial infectivity of primary human keratinocytes. We show that, upon infection of primary human keratinocytes with HPV18 quasivirus, Brd4 activates viral transcription and replication. Furthermore, this activation is independent of the functional interaction between Brd4 and the HPV18 E2 protein.
IMPORTANCE HPVs lack encapsidated proteins and so rely exquisitely on host cellular factors to initiate their gene expression programs in newly infected cells. Brd4 is an important cellular chromatin adaptor molecule that normally activates host transcription initiation and elongation. In this study, we further optimize and utilize a quasivirus infection system to show that Brd4 activates HPV18 transcription at early stages of infection. HPVs are important human pathogens causing a wide range of cutaneous and tumorigenic morbidities. Therefore, specifically targeting this protein could provide a new target of therapeutic prevention of establishment of HPV infections.
C1 [McKinney, Caleb C.; Kim, Min Jung; Chen, Dan; McBride, Alison A.] NIAID, Viral Dis Lab, Bethesda, MD 20892 USA.
[McKinney, Caleb C.] Georgetown Univ, Biomed Grad Educ, Washington, DC USA.
[Kim, Min Jung] Columbia Univ, Microbiol & Immunol, New York, NY USA.
RP McBride, AA (reprint author), NIAID, Viral Dis Lab, Bethesda, MD 20892 USA.
EM amcbride@nih.gov
FU HHS | NIH | National Institute of Allergy and Infectious Diseases
(NIAID) [ZIA AI000713]
FX This work, including the efforts of Caleb C. McKinney, Min Jung Kim, Dan
Chen, and Alison A. McBride, was funded by HHS | NIH | National
Institute of Allergy and Infectious Diseases (NIAID) (ZIA AI000713).
NR 55
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U1 0
U2 0
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 2150-7511
J9 MBIO
JI mBio
PD NOV-DEC
PY 2016
VL 7
IS 6
AR e01644
DI 10.1128/mBio.01644-16
PG 12
WC Microbiology
SC Microbiology
GA EH9GK
UT WOS:000392079500042
ER
PT J
AU Smith, EP
Miller, CN
Child, R
Cundiff, JA
Celli, J
AF Smith, Erin P.
Miller, Cheryl N.
Child, Robert
Cundiff, Jennifer A.
Celli, Jean
TI Postreplication Roles of the Brucella VirB Type IV Secretion System
Uncovered via Conditional Expression of the VirB11 ATPase
SO MBIO
LA English
DT Article
ID INTRACELLULAR REPLICATION; ENDOPLASMIC-RETICULUM; CONTAINING VACUOLE;
GENE-EXPRESSION; TRAFFICKING; MACROPHAGES; CELLS; IDENTIFICATION;
PATHWAY; PROTEIN
AB Brucella abortus, the bacterial agent of the worldwide zoonosis brucellosis, primarily infects host phagocytes, where it undergoes an intracellular cycle within a dedicated membrane-bound vacuole, the Brucella-containing vacuole (BCV). Initially of endosomal origin (eBCV), BCVs are remodeled into replication-permissive organelles (rBCV) derived from the host endoplasmic reticulum, a process that requires modulation of host secretory functions via delivery of effector proteins by the Brucella VirB type IV secretion system (T4SS). Following replication, rBCVs are converted into autophagic vacuoles (aBCVs) that facilitate bacterial egress and subsequent infections, arguing that the bacterium sequentially manipulates multiple cellular pathways to complete its cycle. The VirB T4SS is essential for rBCV biogenesis, as VirB-deficient mutants are stalled in eBCVs and cannot mediate rBCV biogenesis. This has precluded analysis of whether the VirB apparatus also drives subsequent stages of the Brucella intracellular cycle. To address this issue, we have generated a B. abortus strain in which VirB T4SS function is conditionally controlled via anhydrotetracycline (ATc)-dependent complementation of a deletion of the virB11 gene encoding the VirB11 ATPase. We show in murine bone marrow-derived macrophages (BMMs) that early VirB production is essential for optimal rBCV biogenesis and bacterial replication. Transient expression of virB11 prior to infection was sufficient to mediate normal rBCV biogenesis and bacterial replication but led to T4SS inactivation and decreased aBCV formation and bacterial release, indicating that these postreplication stages are also T4SS dependent. Hence, our findings support the hypothesis of additional, postreplication roles of type IV secretion in the Brucella intracellular cycle.
IMPORTANCE Many intracellular bacterial pathogens encode specialized secretion systems that deliver effector proteins into host cells to mediate the multiple stages of their intracellular cycles. Because these intracellular events occur sequentially, classical genetic approaches cannot address the late roles that these apparatuses play, as secretion-deficient mutants cannot proceed past their initial defect. Here we have designed a functionally controllable VirB type IV secretion system (T4SS) in the bacterial pathogen Brucella abortus to decipher its temporal requirements during the bacterium's intracellular cycle in macrophages. By controlling production of the VirB11 ATPase, which energizes the T4SS, we show not only that this apparatus is required early to generate the Brucella replicative organelle but also that it contributes to completion of the bacterium's cycle and bacterial egress. Our findings expand upon the pathogenic functions of the Brucella VirB T4SS and illustrate targeting of secretion ATPases as a useful strategy to manipulate the activity of bacterial secretion systems.
C1 [Smith, Erin P.; Miller, Cheryl N.; Cundiff, Jennifer A.; Celli, Jean] Washington State Univ, Coll Vet Med, Paul G Allen Sch Global Anim Hlth, Pullman, WA 99164 USA.
[Child, Robert; Celli, Jean] NIAID, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA.
[Child, Robert] Univ Montana, Missoula, MT 59812 USA.
RP Celli, J (reprint author), Washington State Univ, Coll Vet Med, Paul G Allen Sch Global Anim Hlth, Pullman, WA 99164 USA.; Celli, J (reprint author), NIAID, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA.
EM jcelli@vetmed.wsu.edu
FU HHS | NIH | National Institute of Allergy and Infectious Diseases
(NIAID) [AI112649]; HHS | NIH | National Institute of General Medical
Sciences (NIGMS) [AI007025]; Division of Intramural Research, National
Institute of Allergy and Infectious Diseases (DIR, NIAID)
FX This work, including the efforts of Jean Celli, was funded by HHS | NIH
| National Institute of Allergy and Infectious Diseases (NIAID)
(AI112649). This work, including the efforts of Cheryl N. Miller, was
funded by HHS | NIH | National Institute of General Medical Sciences
(NIGMS) (AI007025). This work, including the efforts of Jean Celli, was
funded by Division of Intramural Research, National Institute of Allergy
and Infectious Diseases (DIR, NIAID).
NR 28
TC 0
Z9 0
U1 2
U2 2
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 2150-7511
J9 MBIO
JI mBio
PD NOV-DEC
PY 2016
VL 7
IS 6
AR e01730
DI 10.1128/mBio.01730-16
PG 10
WC Microbiology
SC Microbiology
GA EH9GK
UT WOS:000392079500049
ER
PT J
AU Roongpiboonsopit, D
Charidimou, A
William, CM
Lauer, A
Falcone, GJ
Martinez-Ramirez, S
Biffi, A
Ayres, A
Vashkevich, A
Awosika, OO
Rosand, J
Gurol, ME
Silverman, SB
Greenberg, SM
Viswanathan, A
AF Roongpiboonsopit, Duangnapa
Charidimou, Andreas
William, Christopher M.
Lauer, Arne
Falcone, Guido J.
Martinez-Ramirez, Sergi
Biffi, Alessandro
Ayres, Alison
Vashkevich, Anastasia
Awosika, Oluwole O.
Rosand, Jonathan
Gurol, M. Edip
Silverman, Scott B.
Greenberg, Steven M.
Viswanathan, Anand
TI Cortical superficial siderosis predicts early recurrent lobar hemorrhage
SO NEUROLOGY
LA English
DT Article
ID CEREBRAL AMYLOID ANGIOPATHY; PRIMARY INTRACEREBRAL HEMORRHAGE; TRANSIENT
ISCHEMIC ATTACK; SUBARACHNOID HEMORRHAGE; APOLIPOPROTEIN-E;
BLOOD-PRESSURE; WARNING SIGN; RISK; DISEASE
AB Objective: To identify predictors of early lobar intracerebral hemorrhage (ICH) recurrence, defined as a new ICH within 6 months of the index event, in patients with cerebral amyloid angiopathy (CAA).
Methods: Participants were consecutive survivors (age >= 55 years) of spontaneous symptomatic probable or possible CAA-related lobar ICH according to the Boston criteria, drawn from an ongoing single-center cohort study. Neuroimaging markers ascertained in CT or MRI included focal (<= 3 sulci) or disseminated (>3 sulci) cortical superficial siderosis (cSS), acute convexity subarachnoid hemorrhage (cSAH), cerebral microbleeds, white matter hyperintensities burden and location, and baseline ICH volume. Participants were followed prospectively for recurrent symptomatic ICH. Cox proportional hazards models were used to identify predictors of early recurrent ICH adjusting for potential confounders.
Results: A total of 292 patients were enrolled. Twenty-one patients (7%) had early recurrent ICH. Of these, 24% had disseminated cSS on MRI and 19% had cSAH on CT scan. In univariable analysis, the presence of disseminated cSS, cSAH, and history of previous ICH were predictors of early recurrent ICH (p < 0.05 for all comparisons). After adjusting for age and history of previous ICH, disseminated cSS on MRI and cSAH on CT were independent predictors of early recurrent ICH (hazard ratio [HR] 3.92, 95% confidence interval [CI] 1.38-11.17, p = 0.011, and HR 3.48, 95% CI 1.13-10.73, p = 0.030, respectively).
Conclusions: Disseminated cSS on MRI and cSAH on CT are independent imaging markers of increased risk for early recurrent ICH. These markers may provide additional insights into the mechanisms of ICH recurrence in patients with CAA.
C1 [Roongpiboonsopit, Duangnapa; Charidimou, Andreas; Lauer, Arne; Falcone, Guido J.; Martinez-Ramirez, Sergi; Ayres, Alison; Vashkevich, Anastasia; Gurol, M. Edip; Silverman, Scott B.; Greenberg, Steven M.; Viswanathan, Anand] Harvard Med Sch, Massachusetts Gen Hosp, J Philip Kistler Stroke Res Ctr, Hemorrhag Stroke Res Program, Boston, MA 02115 USA.
[Biffi, Alessandro] Harvard Med Sch, Massachusetts Gen Hosp, Dept Neurol, Div Behav Neurol, Boston, MA USA.
[Biffi, Alessandro] Harvard Med Sch, Massachusetts Gen Hosp, Dept Psychiat, Div Neuropsychiat, Boston, MA USA.
[William, Christopher M.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Pathol, Neuropathol Serv, Boston, MA USA.
[Falcone, Guido J.; Rosand, Jonathan] Harvard Med Sch, Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA USA.
[Roongpiboonsopit, Duangnapa] Naresuan Univ, Fac Med, Dept Med, Phitsanulok, Thailand.
[Awosika, Oluwole O.] NINDS, Human Cort Physiol & Stroke Neurorehabil Sect, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
RP Roongpiboonsopit, D (reprint author), Harvard Med Sch, Massachusetts Gen Hosp, J Philip Kistler Stroke Res Ctr, Hemorrhag Stroke Res Program, Boston, MA 02115 USA.; Roongpiboonsopit, D (reprint author), Naresuan Univ, Fac Med, Dept Med, Phitsanulok, Thailand.
EM duangnapar@nu.ac.th
FU NIH [R01AG047975, R01AG026484, P50AG005134, K23AG028726, K23 NS083711,
R01 NS070834]
FX Supported by NIH (R01AG047975, R01AG026484, P50AG005134, K23AG028726,
K23 NS083711, and R01 NS070834).
NR 33
TC 1
Z9 1
U1 2
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0028-3878
EI 1526-632X
J9 NEUROLOGY
JI Neurology
PD NOV 1
PY 2016
VL 87
IS 18
BP 1863
EP 1870
DI 10.1212/WNL.0000000000003281
PG 8
WC Clinical Neurology
SC Neurosciences & Neurology
GA EI1JG
UT WOS:000392232600008
PM 27694268
ER
PT J
AU Bruce, BB
Digre, KB
McDermott, MP
Schron, EB
Wall, M
AF Bruce, Beau B.
Digre, Kathleen B.
McDermott, Michael P.
Schron, Eleanor B.
Wall, Michael
CA NORDIC Idiopathic Intracranial
TI Quality of life at 6 months in the Idiopathic Intracranial Hypertension
Treatment Trial
SO NEUROLOGY
LA English
DT Article
ID PSEUDOTUMOR CEREBRI; DIAGNOSIS
AB Objective: To examine the changes in vision-specific and overall health-related quality of life (QOL) at 6 months in participants with idiopathic intracranial hypertension (IIH) and mild visual loss enrolled in the Idiopathic Intracranial Hypertension Treatment Trial (IIHTT) and to determine the signs and symptoms of IIH that mediate the effect of acetazolamide on QOL.
Methods: We assessed QOL using the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25), the 10-Item NEI-VFQ-25 Neuro-Ophthalmic Supplement, and the 36-Item Short Form Health Survey (SF-36). We examined associations among changes in QOL measures over 6 months, treatment status, and changes in signs and symptoms using linear and structural equation models.
Results: Among the 165 participants with IIH (86 randomized to acetazolamide, 79 to placebo), beneficial effects of acetazolamide were seen on all QOL scales evaluated, as well as on the Near Activities (5.60 points, p = 0.03), Social Functioning (3.85 points, p = 0.04), and Mental Health (9.82, p = 0.04) subscales of the NEI-VFQ-25. Positive acetazolamide-related effects on QOL appeared to be primarily mediated by improvements in visual field, neck pain, pulsatile tinnitus, and dizziness/vertigo that outweighed the side effects of acetazolamide.
Conclusions: The marked reductions in baseline QOL seen among patients with mild visual loss from IIH are improved by treatment with acetazolamide. When combined with acetazolamide-associated improvements in visual field and other aspects of IIH, our findings with respect to QOL provide further support from the IIHTT in favor of acetazolamide to augment a dietary intervention in the treatment of IIH with mild visual loss (clinicaltrials.gov: NCT01003639).
C1 [Bruce, Beau B.] Emory Univ, Dept Ophthalmol, Atlanta, GA 30322 USA.
[Bruce, Beau B.] Emory Univ, Dept Neurol, Atlanta, GA 30322 USA.
[Bruce, Beau B.] Emory Univ, Dept Epidemiol, Atlanta, GA 30322 USA.
[Digre, Kathleen B.] Univ Utah, Moran Eye Ctr, Dept Neurol, Salt Lake City, UT USA.
[Digre, Kathleen B.] Univ Utah, Moran Eye Ctr, Dept Ophthalmol, Salt Lake City, UT USA.
[McDermott, Michael P.] Univ Rochester, Med Ctr, Dept Biostat & Computat Biol, Rochester, NY 14627 USA.
[McDermott, Michael P.] Univ Rochester, Med Ctr, Dept Neurol, Rochester, NY 14627 USA.
[Schron, Eleanor B.] NEI, Div Extramural Res, Bethesda, MD 20892 USA.
[Wall, Michael] Univ Iowa, Carver Coll Med, Dept Ophthalmol & Visual Sci, Iowa City, IA USA.
RP Bruce, BB (reprint author), Emory Univ, Dept Ophthalmol, Atlanta, GA 30322 USA.; Bruce, BB (reprint author), Emory Univ, Dept Neurol, Atlanta, GA 30322 USA.; Bruce, BB (reprint author), Emory Univ, Dept Epidemiol, Atlanta, GA 30322 USA.
EM bbbruce@emory.edu
FU NIH [1U10EY017281-01A1, 1U10EY017387-01A1]; ARRA [3U10EY017281-01A1S1,
1U10EY017387-01A1S1]; Research to Prevent Blindness, Inc., New York, NY;
[3U10EY017281-01A1S2]; [K23EY019341]
FX NIH 1U10EY017281-01A1 and 1U10EY017387-01A1; ARRA for NORDIC
3U10EY017281-01A1S1 and DCBC 1U10EY017387-01A1S1; supplements for NORDIC
3U10EY017281-01A1S2. Dr. Bruce was supported by K23EY019341 and by an
unrestricted grant from Research to Prevent Blindness, Inc., New York,
NY, to the Department of Ophthalmology at Emory University. Dr. Digre
was supported in part by an unrestricted grant from Research to Prevent
Blindness, Inc., New York, NY, to the Department of Ophthalmology and
Visual Sciences, University of Utah, Salt Lake City.
NR 17
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0028-3878
EI 1526-632X
J9 NEUROLOGY
JI Neurology
PD NOV 1
PY 2016
VL 87
IS 18
BP 1871
EP 1877
DI 10.1212/WNL.0000000000003280
PG 7
WC Clinical Neurology
SC Neurosciences & Neurology
GA EI1JG
UT WOS:000392232600009
PM 27694262
ER
PT J
AU Naidoo, J
Panday, H
Jackson, S
Grossman, SA
AF Naidoo, Jarushka
Panday, Hardik
Jackson, Sadhana
Grossman, Stuart A.
TI Optimizing the Delivery of Antineoplastic Therapies to the Central
Nervous System
SO ONCOLOGY-NEW YORK
LA English
DT Article
ID BLOOD-BRAIN-BARRIER; CONVECTION-ENHANCED DELIVERY; GUIDED FOCUSED
ULTRASOUND; HIGH-GRADE GLIOMAS; NORMAL RAT-BRAIN; MALIGNANT GLIOMAS;
DRUG-DELIVERY; INTRAARTERIAL CHEMOTHERAPY; GLIOBLASTOMA-MULTIFORME;
RECURRENT GLIOBLASTOMA
AB Despite signifi cant advances in the treatment of systemic cancers, progress in the treatment of primary brain tumors has been quite modest. In addition, an increasing proportion of patients with systemic cancers are presenting with brain-only metastases. These observations highlight the critical role that the blood-brain barrier plays in preventing antineoplastic therapies from reaching the central nervous system in therapeutic concentrations. This review describes the anatomy of the blood-brain barrier and currently available methods to quantify the entry of therapeutic compounds into the brain. It also summarizes data from a variety of approaches designed to improve drug delivery to the central nervous system. These include: 1) directly placing drugs inside the blood-brain barrier (polymeric implants, convection-enhanced delivery, and intraventricular administration), 2) modifying systemic chemotherapy (by using high-dose methotrexate and intra-arterial drug administration), 3) temporary disruption of the blood-brain barrier (via use of intra-arterial mannitol, focused ultrasound, or pharmacologic agents), and 4) designing drugs that can pass through the blood-brain barrier. Given that lymphocytes readily traverse the blood-brain barrier, immunotherapy represents a novel approach to cancer therapy that is of particular interest to practitioners in the field of neurooncology. The efficacy of vaccines and immune checkpoint inhibitors is currently being actively investigated in patients with primary and metastatic brain tumors, as well as leptomeningeal carcinomatosis. The challenge of delivering effective antineoplastic therapies to the central nervous system remains a primary obstacle to improving outcomes in patients with primary and metastatic brain tumors.
C1 [Naidoo, Jarushka; Grossman, Stuart A.] Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA.
[Panday, Hardik] All India Inst Med Sci, New Delhi, India.
[Jackson, Sadhana] NCI, Neurooncol Branch, Bethesda, MD 20892 USA.
RP Grossman, SA (reprint author), Johns Hopkins Univ, Sch Med, 1550 Orleans St,Suite 1M-16, Baltimore, MD 21287 USA.
EM grossman@jhmi.edu
NR 51
TC 1
Z9 1
U1 0
U2 0
PU UBM MEDICA
PI NORWALK
PA 535 CONNECTICUT AVE, STE 300, NORWALK, CT 06854 USA
SN 0890-9091
J9 ONCOLOGY-NY
JI Oncology-NY
PD NOV
PY 2016
VL 30
IS 11
BP 953
EP 962
PG 10
WC Oncology
SC Oncology
GA EI0WC
UT WOS:000392194900002
ER
PT J
AU D'Souza, G
Anantharaman, D
Gheit, T
Abedi-Ardekani, B
Beachler, DC
Conway, DI
Olshan, AF
Wunsch, V
Toporcov, TN
Ahrens, W
Wisniewski, K
Merletti, F
Boccia, S
Tajara, EH
Zevallos, JP
Levi, JE
Weissler, MC
Wright, S
Scelo, G
Mazul, AL
Tommasino, M
Cadoni, G
Brennan, P
AF D'Souza, Gypsyamber
Anantharaman, Devasena
Gheit, Tarik
Abedi-Ardekani, Behnoush
Beachler, Daniel C.
Conway, David I.
Olshan, Andrew F.
Wunsch-Filho, Victor
Toporcov, Tatiana N.
Ahrens, Wolfgang
Wisniewski, Kathy
Merletti, Franco
Boccia, Stefania
Tajara, Eloiza H.
Zevallos, Jose P.
Levi, Jose Eduardo
Weissler, Mark C.
Wright, Sylvia
Scelo, Ghislaine
Mazul, Angela L.
Tommasino, Massimo
Cadoni, Gabriella
Brennan, Paul
TI Effect of HPV on head and neck cancer patient survival, by region and
tumor site: A comparison of 1362 cases across three continents
SO ORAL ONCOLOGY
LA English
DT Article
DE HPV; P16; Survival; HNSCC; Oral HPV; Non-OP; Prognostic; Risk factors;
Brazil; Europe
ID SQUAMOUS-CELL CARCINOMA; HUMAN-PAPILLOMAVIRUS INFECTION; OROPHARYNGEAL
CANCER; PROGNOSTIC-SIGNIFICANCE; METAANALYSIS; PREVALENCE; P16(INK4A);
BIOMARKERS; SMOKING; EXPRESSION
AB Objectives: To explore whether HPV-related biomarkers predict oropharyngeal squamous cell cancer (OPSCC) survival similarly across different global regions, and to explore their prognostic utility among non-oropharyngeal (non-OP) head and neck cancers.
Methods: Data from 1362 head and neck SCC (HNSCC) diagnosed 2002-2011 was used from epidemiologic studies in: Brazil (GENCAPO study, n = 388), U.S. (CHANCE study, n = 472), and Europe (ARCAGE study, n = 502). Tumors were centrally tested for p16(INK4a) and HPV16 DNA (by PCR). Risk of mortality was examined using Cox proportional hazard models.
Results: There were 517 OPSCC and 845 non-OP HNSCC. Cases were primarily male (81%), ever smokers (91%), with median age of 58 years and median follow-up of 3.1 years (IQR = 1.4-5.9). Among OPSCC, the risk of mortality was significantly lower among 184 HPV-related (i.e., p16(+)/HPV16(+)) compared to 333 HPV-unrelated (p16-and/or HPV16-) cases (HR = 0.25, 95% CI = 0.18-0.34). Mortality was reduced among HPV-related OPSCC cases from the U.S., Europe, and Brazil (each p <= 0.01) and after adjustment, remained significantly reduced (aHR = 0.34, 95% CI = 0.24-0.49). Among non-OP HNSCC, neither p16 (aHR = 0.83, 95% CI = 0.60-1.14), HPV16 DNA (aHR = 1.20, 95% CI = 0.89-1.63), or p16+/HPV16+ (aHR = 0.59, 95% CI = 0.32-1.08) was a significantly predictor of mortality. When interaction was tested, the effect of HPV16/p16 was significantly different in OPSCC than non-OP HNSCC (p-interaction = 0.02).
Conclusion: HPV-related OPSCCs had similar survival benefits across these three regions. Prognostic utility of HPV among non-OP HNSCC is limited so tumor HPV/p16 testing should not be routinely done among non-OP HNSCC. (C) 2016 Elsevier Ltd. All rights reserved.
C1 [D'Souza, Gypsyamber] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
[Anantharaman, Devasena; Scelo, Ghislaine; Brennan, Paul] Int Agcy Res Canc, Genet Epidemiol Grp, Lyon, France.
[Gheit, Tarik; Tommasino, Massimo] Int Agcy Res Canc, Infect & Canc Biol Grp, Lyon, France.
[Abedi-Ardekani, Behnoush] Int Agcy Res Canc, Genet Canc Susceptibil Grp, Lyon, France.
[Beachler, Daniel C.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Conway, David I.] Univ Glasgow, Sch Med Dent & Nursing, Glasgow, Lanark, Scotland.
[Olshan, Andrew F.; Wisniewski, Kathy; Mazul, Angela L.] Univ North Carolina Chapel Hill, Dept Epidemiol, Chapel Hill, NC USA.
[Wunsch-Filho, Victor; Toporcov, Tatiana N.] Univ Sao Paulo, Sch Publ Hlth, Dept Epidemiol, Sao Paulo, Brazil.
[Ahrens, Wolfgang] Leibniz Inst Prevent Res & Epidemiol BIPS, Bremen, Germany.
[Ahrens, Wolfgang] Univ Bremen, Inst Stat, Bremen, Germany.
[Merletti, Franco] Univ Turin, Dept Med Sci, Turin, Italy.
[Boccia, Stefania] Univ Cattolica Sacro Cuore, Fac Med, Inst Publ Hlth, Sect Hyg, Rome, Italy.
[Tajara, Eloiza H.] Fac Med Sao Jose Rio Preto, Dept Mol Biol, Rome, Italy.
[Zevallos, Jose P.; Weissler, Mark C.] Univ North Carolina Chapel Hill, Dept Otolaryngol Head & Neck Surg, Chapel Hill, NC USA.
[Levi, Jose Eduardo] Univ Sao Paulo, Inst Trop Med, Virol Lab, Sao Paulo, Brazil.
[Wright, Sylvia] Queen Elizabeth Univ Hosp, Dept Pathol, Glasgow, Lanark, Scotland.
[Cadoni, Gabriella] Univ Cattolica Sacro Cuore, Fdn Policlin A Gemelli, Inst Otorhinolaryngol, Head & Neck Surg Dept, Rome, Italy.
RP D'Souza, G (reprint author), Johns Hopkins Sch Publ Hlth, 615 N Wolfe St, Baltimore, MD 21205 USA.; Brennan, P (reprint author), Int Agcy Res Canc, 150 Cours Albert Thomas, F-69372 Lyon 08, France.
EM gdsouza2@jhu.edu; brennan@iarc.fr
OI Ahrens, Wolfgang/0000-0003-3777-570X
FU FAPESP; National Cancer Institute; European Framework Programs; French
Health Ministry; Italian AIRC
FX This work was support by FAPESP, National Cancer Institute, European
Framework Programs, French Health Ministry, and Italian AIRC.
NR 28
TC 1
Z9 1
U1 1
U2 1
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1368-8375
EI 1879-0593
J9 ORAL ONCOL
JI Oral Oncol.
PD NOV
PY 2016
VL 62
BP 20
EP 27
DI 10.1016/j.oraloncology.2016.09.005
PG 8
WC Oncology; Dentistry, Oral Surgery & Medicine
SC Oncology; Dentistry, Oral Surgery & Medicine
GA EI6VL
UT WOS:000392635300006
PM 27865368
ER
PT J
AU Alibhai, J
Blanco, RA
Barria, MA
Piccardo, P
Caughey, B
Perry, VH
Freeman, TC
Manson, JC
AF Alibhai, James
Blanco, Richard A.
Barria, Marcelo A.
Piccardo, Pedro
Caughey, Byron
Perry, V. Hugh
Freeman, Tom C.
Manson, Jean C.
TI Distribution of Misfolded Prion Protein Seeding Activity Alone Does Not
Predict Regions of Neurodegeneration
SO PLOS BIOLOGY
LA English
DT Article
ID TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHY; GENE-EXPRESSION PROFILES;
ALZHEIMERS-DISEASE; MICROGLIAL ACTIVATION; IN-VIVO; SCRAPIE; MICE; PRP;
ABSENCE; PROGRESSION
AB Protein misfolding is common across many neurodegenerative diseases, with misfolded proteins acting as seeds for "prion-like" conversion of normally folded protein to abnormal conformations. A central hypothesis is that misfolded protein accumulation, spread, and distribution are restricted to specific neuronal populations of the central nervous system and thus predict regions of neurodegeneration. We examined this hypothesis using a highly sensitive assay system for detection of misfolded protein seeds in a murine model of prion disease. Misfolded prion protein (PrP) seeds were observed widespread throughout the brain, accumulating in all brain regions examined irrespective of neurodegeneration. Importantly, neither time of exposure nor amount of misfolded protein seeds present determined regions of neurodegeneration. We further demonstrate two distinct microglia responses in prioninfected brains: a novel homeostatic response in all regions and an innate immune response restricted to sites of neurodegeneration. Therefore, accumulation of misfolded prion protein alone does not define targeting of neurodegeneration, which instead results only when misfolded prion protein accompanies a specific innate immune response.
C1 [Alibhai, James; Blanco, Richard A.; Piccardo, Pedro; Freeman, Tom C.; Manson, Jean C.] Univ Edinburgh, Roslin Inst, Edinburgh, Midlothian, Scotland.
[Alibhai, James; Blanco, Richard A.; Piccardo, Pedro; Freeman, Tom C.; Manson, Jean C.] Univ Edinburgh, Royal Dick Sch Vet Studies, Edinburgh, Midlothian, Scotland.
[Barria, Marcelo A.] Univ Edinburgh, Western Gen Hosp, Ctr Clin Brain Sci, Natl CJD Res & Surveillance Unit, Edinburgh, Midlothian, Scotland.
[Caughey, Byron] NIAID, Persistent Viral Dis Lab, NIH, Rocky Mt Labs, Hamilton, MT USA.
[Perry, V. Hugh] Univ Southampton, Ctr Biol Sci, Southampton, Hants, England.
RP Manson, JC (reprint author), Univ Edinburgh, Roslin Inst, Edinburgh, Midlothian, Scotland.; Manson, JC (reprint author), Univ Edinburgh, Royal Dick Sch Vet Studies, Edinburgh, Midlothian, Scotland.
EM jean.manson@roslin.ed.ac.uk
FU Biotechnology and Biological Sciences Research Council (BBSRC) DTA
studentship [BB/F01693X/1]; BBSRC Institute Strategic Grant
[BB/J004332/1]
FX This work was funded by Biotechnology and Biological Sciences Research
Council (BBSRC) DTA studentship (BB/F01693X/1) and BBSRC Institute
Strategic Grant (BB/J004332/1). The funders had no role in study design,
data collection and analysis, decision to publish, or preparation of the
manuscript
NR 57
TC 1
Z9 1
U1 2
U2 2
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1545-7885
J9 PLOS BIOL
JI PLoS. Biol.
PD NOV
PY 2016
VL 14
IS 11
AR e1002579
DI 10.1371/journal.pbio.1002579
PG 25
WC Biochemistry & Molecular Biology; Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
Topics
GA EH9TH
UT WOS:000392113500014
PM 27880767
ER
PT J
AU Happel, C
Ramalingam, D
Ziegelbauer, JM
AF Happel, Christine
Ramalingam, Dhivya
Ziegelbauer, Joseph M.
TI Virus-Mediated Alterations in miRNA Factors and Degradation of Viral
miRNAs by MCPIP1
SO PLOS BIOLOGY
LA English
DT Article
ID SARCOMA-ASSOCIATED HERPESVIRUS; INFLAMMATORY-CYTOKINE EXPRESSION;
BINDING PROTEIN AUF1; MESSENGER-RNA DECAY; KAPPA-B ACTIVATION;
KAPOSIS-SARCOMA; CELL-LINES; MICRORNAS; INFECTION; REVEALS
AB Kaposi's sarcoma-associated herpesvirus (KSHV), the causative agent of Kaposi's sarcoma, encodes 25 mature viral miRNAs. MCP-1-induced protein-1 (MCPIP1), a critical regulator of immune homeostasis, has been shown to suppress miRNA biosynthesis via cleavage of precursor miRNAs through its RNase domain. We demonstrate that MCPIP1 can directly cleave KSHV and EBV precursor miRNAs and that MCPIP1 expression is repressed following de novo KSHV infection. In addition, repression with siRNAs to MCPIP1 in KSHV-infected cells increased IL-6 and KSHV miRNA expression, supporting a role for MCPIP1 in IL-6 and KSHV miRNA regulation. We also provide evidence that KSHV miRNAs repress MCPIP1 expression by targeting the 3'UTR of MCPIP1. Conversely, expression of essential miRNA biogenesis components Dicer and TRBP is increased following latent KSHV infection. We propose that KSHV infection inhibits a negative regulator of miRNA biogenesis (MCPIP1) and up-regulates critical miRNA processing components to evade host mechanisms that inhibit expression of viral miRNAs. KSHV-mediated alterations in miRNA biogenesis represent a novel mechanism by which KSHV interacts with its host and a new mechanism for the regulation of viral miRNA expression.
C1 [Happel, Christine; Ramalingam, Dhivya; Ziegelbauer, Joseph M.] NCI, HIV & AIDS Malignancy Branch, NIH, Bethesda, MD 20892 USA.
RP Ziegelbauer, JM (reprint author), NCI, HIV & AIDS Malignancy Branch, NIH, Bethesda, MD 20892 USA.
EM ziegelbauerjm@mail.nih.gov
OI Ziegelbauer, Joseph/0000-0001-6464-6941
FU National Cancer Institute [1ZIABC011176]; Intramural Research Program of
the Center for Cancer Research, National Cancer Institute, National
Institutes of Health
FX National Cancer Institute (grant number 1ZIABC011176).(Received by JZ)
This work was supported by the Intramural Research Program of the Center
for Cancer Research, National Cancer Institute, National Institutes of
Health. The funder had no role in study design, data collection and
analysis, decision to publish, or preparation of the manuscript.
NR 48
TC 0
Z9 0
U1 1
U2 1
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1545-7885
J9 PLOS BIOL
JI PLoS. Biol.
PD NOV
PY 2016
VL 14
IS 11
AR e2000998
DI 10.1371/journal.pbio.2000998
PG 23
WC Biochemistry & Molecular Biology; Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
Topics
GA EH9TH
UT WOS:000392113500019
PM 27893764
ER
PT J
AU Zhang, XL
Japee, S
Safiullah, Z
Mlynaryk, N
Ungerleider, LG
AF Zhang, Xilin
Japee, Shruti
Safiullah, Zaid
Mlynaryk, Nicole
Ungerleider, Leslie G.
TI A Normalization Framework for Emotional Attention
SO PLOS BIOLOGY
LA English
DT Article
ID CONTRAST RESPONSE FUNCTIONS; HUMAN VISUAL-CORTEX; NEURAL MECHANISMS;
DISTRACTOR SUPPRESSION; ORBITOFRONTAL CORTEX; SELECTIVE ATTENTION;
PREFRONTAL NEURONS; EVOKED POTENTIALS; SPATIAL ATTENTION; COVERT
ATTENTION
AB The normalization model of attention proposes that attention can affect performance by response-or contrast-gain changes, depending on the size of the stimulus and attention field. Here, we manipulated the attention field by emotional valence, negative faces versus positive faces, while holding stimulus size constant in a spatial cueing task. We observed changes in the cueing effect consonant with changes in response gain for negative faces and contrast gain for positive faces. Neuroimaging experiments confirmed that subjects' attention fields were narrowed for negative faces and broadened for positive faces. Importantly, across subjects, the self-reported emotional strength of negative faces and positive faces correlated, respectively, both with response-and contrast-gain changes and with primary visual cortex (V1) narrowed and broadened attention fields. Effective connectivity analysis showed that the emotional valence-dependent attention field was closely associated with feedback from the dorsolateral prefrontal cortex (DLPFC) to V1. These findings indicate a crucial involvement of DLPFC in the normalization processes of emotional attention.
C1 [Zhang, Xilin; Japee, Shruti; Safiullah, Zaid; Mlynaryk, Nicole; Ungerleider, Leslie G.] NIMH, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA.
RP Zhang, XL (reprint author), NIMH, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA.
EM xilin.zhang@nih.gov
FU National Institute of Mental Health [NCT00001360]
FX This work was supported by the National Institute of Mental Health
Intramural Research Program (NCT00001360). URL:
http://clinicalstudies.info.nih.gov/cgi/detail.cgi?A_1993-M-0170.html.
The funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 72
TC 1
Z9 1
U1 0
U2 0
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1545-7885
J9 PLOS BIOL
JI PLoS. Biol.
PD NOV
PY 2016
VL 14
IS 11
AR e1002578
DI 10.1371/journal.pbio.1002578
PG 25
WC Biochemistry & Molecular Biology; Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
Topics
GA EH9TH
UT WOS:000392113500008
PM 27870851
ER
PT J
AU Livne, ZB
Alon, S
Vallone, D
Bayleyen, Y
Tovin, A
Shainer, I
Nisembaum, LG
Aviram, I
Smadja-Storz, S
Fuentes, M
Falcon, J
Eisenberg, E
Klein, DC
Burgess, HA
Foulkes, NS
Gothilf, Y
AF Livne, Zohar Ben-Moshe
Alon, Shahar
Vallone, Daniela
Bayleyen, Yared
Tovin, Adi
Shainer, Inbal
Nisembaum, Laura G.
Aviram, Idit
Smadja-Storz, Sima
Fuentes, Michael
Falcon, Jack
Eisenberg, Eli
Klein, David C.
Burgess, Harold A.
Foulkes, Nicholas S.
Gothilf, Yoav
TI Genetically Blocking the Zebrafish Pineal Clock Affects Circadian
Behavior
SO PLOS GENETICS
LA English
DT Article
ID MOUSE PARS TUBERALIS; N-ACETYLTRANSFERASE ACTIVITY; PHOTOENDOCRINE
TRANSDUCTION; PROTEASOMAL PROTEOLYSIS; MELATONIN PRODUCTION; LARVAL
ZEBRAFISH; GENE-EXPRESSION; LIGHT; RHYTHMS; GLAND
AB The master circadian clock in fish has been considered to reside in the pineal gland. This dogma is challenged, however, by the finding that most zebrafish tissues contain molecular clocks that are directly reset by light. To further examine the role of the pineal gland oscillator in the zebrafish circadian system, we generated a transgenic line in which the molecular clock is selectively blocked in the melatonin-producing cells of the pineal gland by a dominant-negative strategy. As a result, clock-controlled rhythms of melatonin production in the adult pineal gland were disrupted. Moreover, transcriptome analysis revealed that the circadian expression pattern of the majority of clock-controlled genes in the adult pineal gland is abolished. Importantly, circadian rhythms of behavior in zebrafish larvae were affected: rhythms of place preference under constant darkness were eliminated, and rhythms of locomotor activity under constant dark and constant dim light conditions were markedly attenuated. On the other hand, global peripheral molecular oscillators, as measured in whole larvae, were unaffected in this model. In conclusion, characterization of this novel transgenic model provides evidence that the molecular clock in the melatonin-producing cells of the pineal gland plays a key role, possibly as part of a multiple pacemaker system, in modulating circadian rhythms of behavior.
C1 [Livne, Zohar Ben-Moshe; Alon, Shahar; Tovin, Adi; Shainer, Inbal; Aviram, Idit; Smadja-Storz, Sima; Gothilf, Yoav] Tel Aviv Univ, George S Wise Fac Life Sci, Dept Neurobiol, Tel Aviv, Israel.
[Alon, Shahar; Eisenberg, Eli; Gothilf, Yoav] Tel Aviv Univ, Sagol Sch Neurosci, Tel Aviv, Israel.
[Vallone, Daniela; Foulkes, Nicholas S.] Karlsruhe Inst Technol, Inst Toxicol & Genet, Eggenstein Leopoldshafen, Germany.
[Bayleyen, Yared; Burgess, Harold A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Unit Behav Neurogenet, NIH, Bethesda, MD USA.
[Nisembaum, Laura G.; Fuentes, Michael; Falcon, Jack] UPMC Univ Paris 06, Sorbonne Univ, Observ Oceanol, CNRS,Biol Integrat Organismes Marins, Banyuls Sur Mer, France.
[Eisenberg, Eli] Tel Aviv Univ, Raymond & Beverly Sackler Sch Phys & Astron, Tel Aviv, Israel.
[Klein, David C.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Neuroendocrinol, NIH, Bethesda, MD USA.
[Klein, David C.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Off Sci Directory, NIH, Bethesda, MD USA.
RP Gothilf, Y (reprint author), Tel Aviv Univ, George S Wise Fac Life Sci, Dept Neurobiol, Tel Aviv, Israel.; Gothilf, Y (reprint author), Tel Aviv Univ, Sagol Sch Neurosci, Tel Aviv, Israel.
EM yoavg@tauex.tau.ac.il
FU United States Israel Binational Science Foundation, Jerusalem, Israel
[2013/433]; Israel Science Foundation, Jerusalem, Israel [1084/12,
443/16]; Helmholtz Association, Germany
FX The United States Israel Binational Science Foundation (grant number
2013/433 to YG and HAB), Jerusalem, Israel; The Israel Science
Foundation (grants number 1084/12 and 443/16 to YG), Jerusalem, Israel.
The BioInterfaces in Technology and Medicine funding programme of the
Helmholtz Association, Germany (to NSF). 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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PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7404
J9 PLOS GENET
JI PLoS Genet.
PD NOV
PY 2016
VL 12
IS 11
AR e1006445
DI 10.1371/journal.pgen.1006445
PG 26
WC Genetics & Heredity
SC Genetics & Heredity
GA EH9ZA
UT WOS:000392129600042
ER
PT J
AU Zhang, Y
Zhang, L
Tang, XN
Bhardwaj, SR
Ji, JY
Rong, YS
AF Zhang, Yi
Zhang, Liang
Tang, Xiaona
Bhardwaj, Shilpa R.
Ji, Jingyun
Rong, Yikang S.
TI MTV, an ssDNA Protecting Complex Essential for Transposon-Based Telomere
Maintenance in Drosophila
SO PLOS GENETICS
LA English
DT Article
ID HOMOLOGOUS RECOMBINATION; TARGETED MUTAGENESIS; PROTEIN; MELANOGASTER;
GENE; HOAP; SPECIALIZATION; REPLICATION; RECRUITMENT; PATHWAYS
AB Multiple complexes protect telomeres. In telomerase-maintained organisms, Shelterin related complexes occupy the duplex region while the CST and Tpp1-Pot1 complexes bind the single stranded overhang of telomeres. Drosophila uses a transposon-based mechanism for end protection. We showed that the HOAP-HipHop complex occupies the duplex region. Whether an ssDNA-binding complex exists is not known. Here we discover a novel protein, Tea, that is specifically enriched at telomeres to prevent telomere fusion. We also identify a complex consisting of Tea and two known capping proteins, Ver and Moi. The Moi-Tea-Ver (MTV) complex purified in vitro binds and protects ssDNA in a sequence-independent manner. Tea recruits Ver and Moi to telomeres, and point mutations disrupting MTV interaction in vitro result in telomere uncapping, consistent with these proteins functioning as a complex in vivo. MTV thus shares functional similarities with CST or TPP1-POT1 in protecting ssDNA, highlighting a conserved feature in end protecting mechanisms.
C1 [Zhang, Yi; Ji, Jingyun; Rong, Yikang S.] Sun Yat Sen Univ, Sch Life Sci, Inst Entomol, State Key Lab Biocontrol, Guangzhou, Guangdong, Peoples R China.
[Zhang, Yi; Zhang, Liang; Tang, Xiaona; Bhardwaj, Shilpa R.; Rong, Yikang S.] NCI, Lab Biochem & Mol Biol, NIH, Bethesda, MD 20892 USA.
RP Rong, YS (reprint author), Sun Yat Sen Univ, Sch Life Sci, Inst Entomol, State Key Lab Biocontrol, Guangzhou, Guangdong, Peoples R China.; Rong, YS (reprint author), NCI, Lab Biochem & Mol Biol, NIH, Bethesda, MD 20892 USA.
EM rongyik@mail.sysu.edu.cn
FU National Cancer Institute, USA; NSFC of China [31371364]
FX This work was supported by the intramural research program of the
National Cancer Institute, USA and subsequently a grant from NSFC of
China (Grant #31371364). The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 36
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PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7404
J9 PLOS GENET
JI PLoS Genet.
PD NOV
PY 2016
VL 12
IS 11
AR e1006435
DI 10.1371/journal.pgen.1006435
PG 14
WC Genetics & Heredity
SC Genetics & Heredity
GA EH9ZA
UT WOS:000392129600036
PM 27835648
ER
PT J
AU Baseler, L
Scott, DP
Saturday, G
Horne, E
Rosenke, R
Thomas, T
Meade-White, K
Haddock, E
Feldmann, H
de Wit, E
AF Baseler, Laura
Scott, Dana P.
Saturday, Greg
Horne, Eva
Rosenke, Rebecca
Thomas, Tina
Meade-White, Kimberly
Haddock, Elaine
Feldmann, Heinz
de Wit, Emmie
TI Identifying Early Target Cells of Nipah Virus Infection in Syrian
Hamsters
SO PLOS NEGLECTED TROPICAL DISEASES
LA English
DT Article
ID CENTRAL-NERVOUS-SYSTEM; CLINICAL-FEATURES; MARGINAL ZONE; PIG-FARMERS;
BANGLADESH; MALAYSIA; TRANSMISSION; ENCEPHALITIS; OUTBREAK; MACROPHAGES
AB Background
Nipah virus causes respiratory and neurologic disease with case fatality rates up to 100% in individual outbreaks. End stage lesions have been described in the respiratory and nervous systems, vasculature and often lymphoid organs in fatal human cases; however, the initial target organs of Nipah virus infection have not been identified. Here, we detected the initial target tissues and cells of Nipah virus and tracked virus dissemination during the early phase of infection in Syrian hamsters inoculated with a Nipah virus isolate from Malaysia (NiV-M) or Bangladesh (NiV-B).
Methodology/Principal Findings
Syrian hamsters were euthanized between 4 and 48 hours post intranasal inoculation and tissues were collected and analyzed for the presence of viral RNA, viral antigen and infectious virus.
Virus replication was first detected at 8 hours post inoculation (hpi). Nipah virus initially targeted type I pneumocytes, bronchiolar respiratory epithelium and alveolar macrophages in the lung and respiratory and olfactory epithelium lining the nasal turbinates. By 16 hpi, virus disseminated to epithelial cells lining the larynx and trachea. Although the pattern of viral dissemination was similar for both virus isolates, the rate of spread was slower for NiV-B. Infectious virus was not detected in the nervous system or blood and widespread vascular infection and lesions within lymphoid organs were not observed, even at 48 hpi.
Conclusions/Significance
Nipah virus initially targets the respiratory system. Virus replication in the brain and infection of blood vessels in non-respiratory tissues does not occur during the early phase of infection. However, virus replicates early in olfactory epithelium and may serve as the first step towards nervous system dissemination, suggesting that development of vaccines that block virus dissemination or treatments that can access the brain and spinal cord and directly inhibit virus replication may be necessary for preventing central nervous system pathology.
C1 [Baseler, Laura; Horne, Eva; Thomas, Tina; Haddock, Elaine; Feldmann, Heinz; de Wit, Emmie] NIAID, Virol Lab, NIH, Hamilton, MT 59840 USA.
[Baseler, Laura] Purdue Univ, Dept Comparat Pathobiol, W Lafayette, IN 47907 USA.
[Scott, Dana P.; Saturday, Greg; Rosenke, Rebecca; Meade-White, Kimberly] NIAID, Rocky Mt Vet Branch, NIH, Hamilton, MT USA.
[Baseler, Laura] Univ Texas MD Anderson Canc Ctr, Dept Vet Med & Surg, Houston, TX 77030 USA.
RP de Wit, E (reprint author), NIAID, Virol Lab, NIH, Hamilton, MT 59840 USA.
EM emmie.dewit@nih.gov
OI de Wit, Emmie/0000-0002-9763-7758
FU Intramural Research Program of the National Institutes of Health,
National Institute of Allergy and Infectious Diseases; National
Institutes of Health Comparative Biomedical Scientist Training Program
FX This work was supported by the Intramural Research Program of the
National Institutes of Health, National Institute of Allergy and
Infectious Diseases. LB was supported in part by the National Institutes
of Health Comparative Biomedical Scientist Training Program. The funders
had no role in study design, data collection and analysis, decision to
publish, or preparation of the manuscript.
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PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1935-2735
J9 PLOS NEGLECT TROP D
JI Plos Neglect. Trop. Dis.
PD NOV
PY 2016
VL 10
IS 11
AR e0005120
DI 10.1371/journal.pntd.0005120
PG 18
WC Infectious Diseases; Parasitology; Tropical Medicine
SC Infectious Diseases; Parasitology; Tropical Medicine
GA EI0HR
UT WOS:000392154400040
PM 27812087
ER
PT J
AU Traore, B
Oliveira, F
Faye, O
Dicko, A
Coulibaly, CA
Sissoko, IM
Sibiry, S
Sogoba, N
Sangare, MB
Coulibaly, YI
Traore, P
Traore, SF
Anderson, JM
Keita, S
Valenzuela, JG
Kamhawi, S
Doumbia, S
AF Traore, Bourama
Oliveira, Fabiano
Faye, Ousmane
Dicko, Adama
Coulibaly, Cheick A.
Sissoko, Ibrahim M.
Sibiry, Samake
Sogoba, Nafomon
Sangare, Moussa Brema
Coulibaly, Yaya I.
Traore, Pierre
Traore, Sekou F.
Anderson, Jennifer M.
Keita, Somita
Valenzuela, Jesus G.
Kamhawi, Shaden
Doumbia, Seydou
TI Prevalence of Cutaneous Leishmaniasis in Districts of High and Low
Endemicity in Mali
SO PLOS NEGLECTED TROPICAL DISEASES
LA English
DT Article
ID THIES AREA SENEGAL; IMMUNE-RESPONSE; MAJOR INFECTION; SENSITIVITY;
ECOLOGY; FOCUS
AB Historically the western sahelian dry regions of Mali are known to be highly endemic for cutaneous leishmaniasis (CL) caused by Leishmania major, while cases are rarely reported from the Southern savanna forest of the country. Here, we report baseline prevalence of CL infection in 3 ecologically distinct districts of Mali (dry sahelian, north savanna and southern savanna forest areas). We screened 195 to 250 subjects from 50 to 60 randomly selected households in each of the 6 villages (four from the western sahelian district of Diema in Kayes region, one from the central district of Kolokani and one from the southern savanna district of Kolodieba, region of Sikasso). The screening consisted of: 1] A Leishmanin Skin Test (LST) for detection of exposure to Leishmania parasites; 2] clinical examination of suspected lesions, followed by validation with PCR and 3] finger prick blood sample to determine antibody levels to sand fly saliva. LST positivity was higher in the western district of Diema (49.9%) than in Kolokani (24.9%) and was much lower in Kolondieba (2.6%). LST positivity increased with age rising from 13.8% to 88% in Diema for age groups 2-5 years and 41-65 years, respectively. All eight PCR-confirmed L. major CL cases were diagnosed in subjects below 18 years of age and all were residents of the district of Diema. Exposure to sand fly bites, measured by anti-saliva antibody titers, was comparable in individuals living in all three districts. However, antibody titers were significantly higher in LST positive individuals (P<0.0001). In conclusion, CL transmission remains active in the western region of Mali where lesions were mainly prevalent among children under 18 years old. LST positivity correlated to higher levels of antibodies to sand fly salivary proteins, suggesting their potential as a risk marker for CL acquisition in Mali.
C1 [Traore, Bourama; Coulibaly, Cheick A.; Sissoko, Ibrahim M.; Sibiry, Samake; Sogoba, Nafomon; Sangare, Moussa Brema; Coulibaly, Yaya I.; Traore, Sekou F.; Doumbia, Seydou] USTTB, Int Ctr Excellence Res ICER MALI, Bamako, Mali.
[Oliveira, Fabiano; Anderson, Jennifer M.; Valenzuela, Jesus G.; Kamhawi, Shaden] NIAID, LMVR, NIH, Rockville, MD USA.
[Faye, Ousmane; Dicko, Adama; Traore, Pierre; Keita, Somita] Ctr Natl Appui Lutte Malad CNAM, Bamako, Mali.
RP Doumbia, S (reprint author), USTTB, Int Ctr Excellence Res ICER MALI, Bamako, Mali.
EM sdoumbi@icermali.org
FU National Institute of Allergy and Infectious Diseases of the National
Institutes of Health [P50AI098505]; Division of Intramural Research
Program of NIAID, National Institutes of Health, Bethesda, MD, USA
FX This work was funded by the National Institute of Allergy and Infectious
Diseases of the National Institutes of Health under Award Number
P50AI098505 (Tropical Medicine Research Center, TMRC) and the Division
of Intramural Research Program of NIAID, National Institutes of Health,
Bethesda, MD, USA. The views expressed in this manuscript are solely
those of the authors and do not necessarily represent the officials
views of the funders. The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 28
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U1 0
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PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1935-2735
J9 PLOS NEGLECT TROP D
JI Plos Neglect. Trop. Dis.
PD NOV
PY 2016
VL 10
IS 11
AR e0005141
DI 10.1371/journal.pntd.0005141
PG 12
WC Infectious Diseases; Parasitology; Tropical Medicine
SC Infectious Diseases; Parasitology; Tropical Medicine
GA EI0HR
UT WOS:000392154400048
PM 27898671
ER
PT J
AU Prodger, JL
Gray, RH
Shannon, B
Shahabi, K
Kong, XR
Grabowski, K
Kigozi, G
Nalugoda, F
Serwadda, D
Wawer, MJ
Reynolds, SJ
Liu, CM
Tobian, AAR
Kaul, R
AF Prodger, Jessica L.
Gray, Ronald H.
Shannon, Brett
Shahabi, Kamnoosh
Kong, Xiangrong
Grabowski, Kate
Kigozi, Godfrey
Nalugoda, Fred
Serwadda, David
Wawer, Maria J.
Reynolds, Steven J.
Liu, Cindy M.
Tobian, Aaron A. R.
Kaul, Rupert
TI Chemokine Levels in the Penile Coronal Sulcus Correlate with HIV-1
Acquisition and Are Reduced by Male Circumcision in Rakai, Uganda
SO PLOS PATHOGENS
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; CD4(+) T-CELLS; ATTRACTANT ACTIVATION
PROTEIN-1; BACTERIAL VAGINOSIS; TH17 CELLS; SEXUAL TRANSMISSION; HUMAN
NEUTROPHILS; TYPE-2 INFECTION; DENDRITIC CELLS; EXPLANT TISSUE
AB Individual susceptibility to HIV is heterogeneous, but the biological mechanisms explaining differences are incompletely understood. We hypothesized that penile inflammation may increase HIV susceptibility in men by recruiting permissive CD4 T cells, and that male circumcision may decrease HIV susceptibility in part by reducing genital inflammation. We used multi-array technology to measure levels of seven cytokines in coronal sulcus (penile) swabs collected longitudinally from initially uncircumcised men enrolled in a randomized trial of circumcision in Rakai, Uganda. Coronal sulcus cytokine levels were compared between men who acquired HIV and controls who remained seronegative. Cytokines were also compared within men before and after circumcision, and correlated with CD4 T cells subsets in foreskin tissue. HIV acquisition was associated with detectable coronal sulcus Interleukin-8 (IL-8 aOR 2.26, 95% CI 1.04 +/- 6.40) and Monokine Induced by.-interferon (MIG aOR 2.72, 95% CI 1.15 +/- 8.06) at the visit prior to seroconversion, and the odds of seroconversion increased with detection of multiple cytokines. Coronal sulcus chemokine levels were not correlated with those in the vagina of a man's female sex partner. The detection of IL-8 in swabs was significantly reduced 6 months after circumcision (PRR 0.59, 95% CI 0.44 +/- 0.87), and continued to decline for at least two years (PRR 0.29, 95% CI 0.16 +/- 0.54). Finally, prepuce IL-8 correlated with increased HIV target cell density in foreskin tissues, including highly susceptible CD4 T cells subsets, as well as with tissue neutrophil density. Together, these data suggest that penile inflammation increases HIV susceptibility and is reduced by circumcision.
C1 [Prodger, Jessica L.; Gray, Ronald H.; Kong, Xiangrong; Grabowski, Kate; Wawer, Maria J.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
[Gray, Ronald H.; Kigozi, Godfrey; Nalugoda, Fred; Serwadda, David; Wawer, Maria J.; Reynolds, Steven J.; Tobian, Aaron A. R.] Rakai Hlth Sci Program, Kalisizo, Uganda.
[Shannon, Brett; Shahabi, Kamnoosh; Kaul, Rupert] Univ Toronto, Dept Med, Toronto, ON, Canada.
[Reynolds, Steven J.] NIAID, Div Intramural Res, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Reynolds, Steven J.] Johns Hopkins Univ, Sch Med, Dept Infect Dis, Baltimore, MD USA.
[Liu, Cindy M.] George Washington Univ, Dept Environm & Occupat Hlth, Washington, DC USA.
[Liu, Cindy M.] Translat Genom Res Inst, Flagstaff, AZ USA.
[Tobian, Aaron A. R.] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA.
RP Kaul, R (reprint author), Univ Toronto, Dept Med, Toronto, ON, Canada.
EM rupert.kaul@utoronto.ca
OI Prodger, Jessica/0000-0003-0805-4196
FU Bill and Melinda Gates Foundation [22006.03]; National Institutes of
Health [R01AI087409-01A1, UO1AI51171, 1UO1AI075115-01A1]; Fogarty
International Center [1D43TWO09578-01]; Canadian Institutes of Health
Research [TMI-138656, 201302MFE-300992-230373]; NIH [1K23AI093152-01A1];
Division of Intramural Research, National Institute of Allergy and
Infectious Diseases, National Institutes of Health
FX Bill and Melinda Gates Foundation, grant number 22006.03; National
Institutes of Health, grant numbers R01AI087409-01A1, UO1AI51171 and
1UO1AI075115-01A1; Fogarty International Center, grant number
1D43TWO09578-01; Canadian Institutes of Health Research, grant number
TMI-138656. JLP was supported by the Canadian Institutes of Health
Research 201302MFE-300992-230373.AART was supported by the NIH
1K23AI093152-01A1. Partial support (SJR) was provided by the Division of
Intramural Research, National Institute of Allergy and Infectious
Diseases, National Institutes of Health. The funders had no role in
study design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 82
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PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7366
EI 1553-7374
J9 PLOS PATHOG
JI PLoS Pathog.
PD NOV
PY 2016
VL 12
IS 11
AR e1006025
DI 10.1371/journal.ppat.1006025
PG 21
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA EI0VO
UT WOS:000392193200045
PM 27898732
ER
PT J
AU Tompkins, VS
Sompallae, R
Rosean, TR
Walsh, S
Acevedo, M
Kovalchuk, AL
Han, SS
Jing, X
Holman, C
Rehg, JE
Herms, S
Sunderland, JS
Morse, HC
Janz, S
AF Tompkins, V. S.
Sompallae, R.
Rosean, T. R.
Walsh, S.
Acevedo, M.
Kovalchuk, A. L.
Han, S-S
Jing, X.
Holman, C.
Rehg, J. E.
Herms, S.
Sunderland, J. S.
Morse, H. C.
Janz, S.
TI Transgenic mouse model of IgM(+) lymphoproliferative disease mimicking
Waldenstrom macroglobulinemia
SO BLOOD CANCER JOURNAL
LA English
DT Article
ID CHRONIC LYMPHOCYTIC-LEUKEMIA; B-CELL LYMPHOMAGENESIS; CYTIDINE DEAMINASE
AID; MULTIPLE-MYELOMA; PLASMA-CELLS; TUMOR MICROENVIRONMENT; EXPRESSION
PATTERNS; GENOMIC LANDSCAPE; CXCR4 MUTATIONS; PRE-B
AB Waldenstrom macroglobulinemia (WM) is a low-grade incurable immunoglobulin M+ (IgM(+)) lymphoplasmacytic lymphoma for which a genetically engineered mouse model of de novo tumor development is lacking. On the basis of evidence that the proinflammatory cytokine, interleukin 6 (IL6), and the survival-enhancing oncoprotein, B cell leukemia 2 (BCL2), have critical roles in the natural history of WM, we hypothesized that the enforced expression of IL6 and BCL2 in mice unable to perform immunoglobulin class switch recombination may result in a lymphoproliferative disease that mimics WM. To evaluate this possibility, we generated compound transgenic BALB/c mice that harbored the human BCL2 and IL6 transgenes, E mu SV-BCL2-22 and H2-L-d-hIL6, on the genetic background of activation-induced cytidine deaminase (AID) deficiency. We designated these mice BCL2(+) IL6(+) AID(-) and found that they developed-with full genetic penetrance (100% incidence) and suitably short latency (93 days median survival)-a severe IgM(+) lymphoproliferative disorder that recapitulated important features of human WM. However, the BCL2(+) IL6(+) AID(-) model also exhibited shortcomings, such as low serum IgM levels and histopathological changes not seen in patients with WM, collectively indicating that further refinements of the model are required to achieve better correlations with disease characteristics of WM.
C1 [Tompkins, V. S.; Sompallae, R.; Rosean, T. R.; Han, S-S; Jing, X.; Holman, C.; Janz, S.] Univ Iowa, Roy J & Lucille A Carver Coll Med, Iowa Inst Human Genet, Dept Pathol, Iowa City, IA 52242 USA.
[Sompallae, R.] Univ Iowa, Roy J & Lucille A Carver Coll Med, Iowa Inst Human Genet, Bioinformat Div, Iowa City, IA USA.
[Walsh, S.; Acevedo, M.; Sunderland, J. S.] Univ Iowa, Dept Radiol, Roy J & Lucille A Carver Coll Med, Iowa City, IA 52242 USA.
[Kovalchuk, A. L.; Morse, H. C.] NIAID, Immunogenet Lab, Virol & Cellular Immunol Sect, NIH, Rockville, MD 20852 USA.
[Rehg, J. E.] St Jude Childrens Res Hosp, Dept Pathol, Memphis, TN 38105 USA.
[Herms, S.] Int Waldenstroms Macroglobulinemia Fdn, Sarasota, FL USA.
RP Janz, S (reprint author), Univ Iowa, Roy J & Lucille A Carver Coll Med, Dept Pathol, 1030 Med Labs, Iowa City, IA 52242 USA.
EM siegfried-janz@uiowa.edu
FU IWMF [2010-1]; NCI [R01CA151354]; NIH [T32-HL07734, T32-AI007485];
ALSAC; Intramural Research Program of the NIH, NIAID; NCI Core Grant of
The University of Iowa Holden Comprehensive Cancer Center [P30CA086862]
FX The technical assistance of Ling Hu and veterinary care provided by
staff of the UI CCOM transgenic mouse facility are gratefully
acknowledged. We thank Drs Torgny Fredrickson and Alicia Olivier for
their expert histopathological advice. This work was funded by IWMF
research grant 2010-1 (SJ). Additional support was provided by NCI
R01CA151354 (SJ), by NIH Training Grants T32-HL07734 (VST) and
T32-AI007485 (TRR), by ALSAC (JER), by the Intramural Research Program
of the NIH, NIAID (HCM and ALK) and by NCI Core Grant P30CA086862 in
support of The University of Iowa Holden Comprehensive Cancer Center.
NR 60
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U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2044-5385
J9 BLOOD CANCER J
JI Blood Cancer J.
PD NOV
PY 2016
VL 6
AR e488
DI 10.1038/bcj.2016.95
PG 11
WC Oncology
SC Oncology
GA EH5IM
UT WOS:000391806500001
PM 27813533
ER
PT J
AU Robinson, LM
Morton, FB
Gartner, MC
Widness, J
Paukner, A
Essler, JL
Brosnan, SF
Weiss, A
AF Robinson, Lauren M.
Morton, F. Blake
Gartner, Marieke C.
Widness, Jane
Paukner, Annika
Essler, Jennifer L.
Brosnan, Sarah F.
Weiss, Alexander
TI Divergent Personality Structures of Brown (Sapajus apella) and
White-Faced Capuchins (Cebus capucinus)
SO JOURNAL OF COMPARATIVE PSYCHOLOGY
LA English
DT Article
DE capuchin; Cebus; New World primates; personality; Sapajus
ID 5-FACTOR MODEL; CHIMPANZEE PERSONALITY; SOCIAL RELATIONSHIPS; ZOOLOGICAL
PARKS; MONKEYS; UNIVERSAL; EVOLUTION; MACAQUES; ROTATION; TRAITS
AB One way to gain insights into personality evolution is by comparing the personality structures of related species. We compared the personality structure of 240 wild white-faced capuchin monkeys to the personality structure of 100 captive brown capuchin monkeys. An ancillary goal was to test the degree to which different personality questionnaires yielded similar personality dimensions. Both species were rated on a common set of 26 antonym pairs. The brown capuchin monkeys were also rated on the 54-item Hominoid Personality Questionnaire. Our cross-species comparisons revealed 3 personality dimensions-Assertiveness, Openness, and Neuroticism-shared by brown and white-faced capuchins, suggesting that these dimensions were present in the common ancestor of these species. Our comparison of the dimensions derived from the antonym pairs and the Hominoid Personality Questionnaire revealed that three common dimensions were identified by both questionnaires. In addition, the dimension Attentiveness was only identified using the Hominoid Personality Questionnaire. These results indicate that major features of capuchin personality are conserved and that the structure of some traits, such as those related to focus, persistence, and attention, diverged. Further work is needed to identify the evolutionary bases that led to the conservation of some dimensions but not others.
C1 [Robinson, Lauren M.; Weiss, Alexander] Univ Edinburgh, Dept Psychol, Sch Philosophy Psychol & Language Sci, 7 George Sq, Edinburgh EH8 9JZ, Midlothian, Scotland.
[Robinson, Lauren M.] Univ Edinburgh, Jeanne Marchig Int Ctr Anim Welf Educ, Royal Dick Sch Vet Studies, Edinburgh EH8 9JZ, Midlothian, Scotland.
[Robinson, Lauren M.; Morton, F. Blake; Weiss, Alexander] Scottish Primate Res Grp, Edinburgh, Midlothian, Scotland.
[Morton, F. Blake] Franklin & Marshall Coll, Dept Psychol, Lancaster, PA 17604 USA.
[Gartner, Marieke C.] Philadelphia Zoo, Philadelphia, PA USA.
[Widness, Jane] Yale Univ, Dept Psychol, New Haven, CT 06520 USA.
[Paukner, Annika] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Comparat Ethol Lab, Bethesda, MD USA.
[Essler, Jennifer L.] Med Univ Vienna, Univ Vet Med Vienna, Messerli Res Inst, Comparat Cognit, Vienna, Austria.
[Essler, Jennifer L.] Univ Vienna, A-1010 Vienna, Austria.
[Brosnan, Sarah F.] Georgia State Univ, Dept Psychol, Atlanta, GA 30303 USA.
RP Robinson, LM (reprint author), Univ Edinburgh, Dept Psychol, Sch Philosophy Psychol & Language Sci, 7 George Sq, Edinburgh EH8 9JZ, Midlothian, Scotland.
EM l.robinson@ed.ac.uk
FU University of Stirling; Primate Society of Great Britain; Division of
Intramural Research, NICHD [Z99 HD999999]
FX First and foremost, we extend a very special thank you to all the raters
across the sites that took the time to fill out the personality
questionnaires for us and the directors of the centers for giving us
permission to research their capuchins: Peter Judge, David Washburn, and
Andy Whiten. We also thank Kelly Leverett and Lara Wood for their help
coordinating our research and Joe Manson for supplying us with white
capuchin component-loading matrices. Particular thanks go to the staff
and students for support and assistance during data collection. We
acknowledge the University of Stirling, Primate Society of Great
Britain, and the Division of Intramural Research, NICHD Z99 HD999999,
for providing funding.
NR 43
TC 0
Z9 0
U1 4
U2 4
PU AMER PSYCHOLOGICAL ASSOC
PI WASHINGTON
PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA
SN 0735-7036
EI 1939-2087
J9 J COMP PSYCHOL
JI J. Comp. Psychol.
PD NOV
PY 2016
VL 130
IS 4
BP 305
EP 312
DI 10.1037/com0000037
PG 8
WC Behavioral Sciences; Psychology; Psychology, Multidisciplinary; Zoology
SC Behavioral Sciences; Psychology; Zoology
GA EC9XG
UT WOS:000388497000001
PM 27841454
ER
PT J
AU Konig, G
Pickard, FC
Huang, J
Simmonett, AC
Tofoleanu, F
Lee, J
Dral, PO
Prasad, S
Jones, M
Shao, YH
Thiel, W
Brooks, BR
AF Koenig, Gerhard
Pickard, Frank C.
Huang, Jing
Simmonett, Andrew C.
Tofoleanu, Florentina
Lee, Juyong
Dral, Pavlo O.
Prasad, Samarjeet
Jones, Michael
Shao, Yihan
Thiel, Walter
Brooks, Bernard R.
TI Calculating distribution coefficients based on multi-scale free energy
simulations: an evaluation of MM and QM/MM explicit solvent simulations
of water-cyclohexane transfer in the SAMPL5 challenge
SO JOURNAL OF COMPUTER-AIDED MOLECULAR DESIGN
LA English
DT Article
DE Distribution coefficient; Partition coefficient; Water; Cyclohexane;
Multi-scale free energy simulations; Explicit solvent
ID SOLVATION FREE-ENERGIES; HYDRATION FREE-ENERGIES; QUANTUM-MECHANICAL
CALCULATIONS; BENNETT REWEIGHTING SCHEMES; DENSITY-FUNCTIONAL THEORY;
ACCEPTANCE RATIO METHOD; SEMIEMPIRICAL METHODS; BLIND PREDICTION;
PERTURBATION METHOD; BINDING AFFINITIES
AB One of the central aspects of biomolecular recognition is the hydrophobic effect, which is experimentally evaluated by measuring the distribution coefficients of compounds between polar and apolar phases. We use our predictions of the distribution coefficients between water and cyclohexane from the SAMPL5 challenge to estimate the hydrophobicity of different explicit solvent simulation techniques. Based on molecular dynamics trajectories with the CHARMM General Force Field, we compare pure molecular mechanics (MM) with quantum-mechanical (QM) calculations based on QM/MM schemes that treat the solvent at the MM level. We perform QM/MM with both density functional theory (BLYP) and semi-empirical methods (OM1, OM2, OM3, PM3). The calculations also serve to test the sensitivity of partition coefficients to solute polarizability as well as the interplay of the quantum-mechanical region with the fixed-charge molecular mechanics environment. Our results indicate that QM/MM with both BLYP and OM2 outperforms pure MM. However, this observation is limited to a subset of cases where convergence of the free energy can be achieved.
C1 [Koenig, Gerhard; Pickard, Frank C.; Huang, Jing; Simmonett, Andrew C.; Tofoleanu, Florentina; Lee, Juyong; Prasad, Samarjeet; Jones, Michael; Shao, Yihan; Brooks, Bernard R.] NHLBI, Lab Computat Biol, NIH, Bldg 10, Bethesda, MD 20892 USA.
[Koenig, Gerhard; Dral, Pavlo O.; Thiel, Walter] Max Planck Inst Kohlenforsch, D-45470 Mulheim, Germany.
RP Konig, G (reprint author), NHLBI, Lab Computat Biol, NIH, Bldg 10, Bethesda, MD 20892 USA.; Konig, G (reprint author), Max Planck Inst Kohlenforsch, D-45470 Mulheim, Germany.
EM gkoenig@mpi-muelheim.mpg.de
RI Thiel, Walter/A-5677-2016; Huang, Jing/G-5320-2011; Dral,
Pavlo/A-6089-2016;
OI Thiel, Walter/0000-0001-6780-0350; Huang, Jing/0000-0001-9639-2907;
Dral, Pavlo/0000-0002-2975-9876; Lee, Juyong/0000-0003-1174-4358
FU National Heart, Lung and Blood Institute of the National Institutes of
Health; European Research Council within an ERC Advanced Grant (OMSQC)
FX The authors would like to thank Tim Miller, Richard Venable and John
Legato for technical assistance. We would also like to thank Richard
Pastor and Richard Venable for very helpful discussions concerning the
nature of the apolar phase, especially in octanol. This work was
partially supported by the intramural research program of the National
Heart, Lung and Blood Institute of the National Institutes of Health and
utilized the high-performance computational capabilities of the LoBoS
and Biowulf Linux clusters at the National Institutes of Health.
(http://www.lobos.nih.gov and http://hpc.nih.gov). The research leading
to these results has also received funding from the European Research
Council within an ERC Advanced Grant (OMSQC).
NR 112
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U2 9
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0920-654X
EI 1573-4951
J9 J COMPUT AID MOL DES
JI J. Comput.-Aided Mol. Des.
PD NOV
PY 2016
VL 30
IS 11
SI SI
BP 989
EP 1006
DI 10.1007/s10822-016-9936-x
PN 1
PG 18
WC Biochemistry & Molecular Biology; Biophysics; Computer Science,
Interdisciplinary Applications
SC Biochemistry & Molecular Biology; Biophysics; Computer Science
GA EH0MU
UT WOS:000391459000006
PM 27577746
ER
PT J
AU Pickard, FC
Konig, G
Tofoleanu, F
Lee, J
Simmonett, AC
Shao, YH
Ponder, JW
Brooks, BR
AF Pickard, Frank C.
Koenig, Gerhard
Tofoleanu, Florentina
Lee, Juyong
Simmonett, Andrew C.
Shao, Yihan
Ponder, Jay W.
Brooks, Bernard R.
TI Blind prediction of distribution in the SAMPL5 challenge with QM based
protomer and pK (a) corrections
SO JOURNAL OF COMPUTER-AIDED MOLECULAR DESIGN
LA English
DT Article
DE Free energy; Partition coefficients; Distribution coefficients;
Non-Boltzmann Bennett; Implicit solvent; SAMPL5; pK(a); Protomer;
Tautomer
ID FREE-ENERGY CALCULATIONS; MOLECULAR-DYNAMICS SIMULATIONS; BENNETT
REWEIGHTING SCHEMES; HYDRATION FREE-ENERGIES; SOLVATION FREE-ENERGIES;
DENSITY FUNCTIONALS; PK(A) CALCULATIONS; CONTINUUM MODEL; DRUG
DISCOVERY; QM/MM APPROACH
AB The computation of distribution coefficients between polar and apolar phases requires both an accurate characterization of transfer free energies between phases and proper accounting of ionization and protomerization. We present a protocol for accurately predicting partition coefficients between two immiscible phases, and then apply it to 53 drug-like molecules in the SAMPL5 blind prediction challenge. Our results combine implicit solvent QM calculations with classical MD simulations using the non-Boltzmann Bennett free energy estimator. The OLYP/DZP/SMD method yields predictions that have a small deviation from experiment (RMSD = 2.3 D units), relative to other participants in the challenge. Our free energy corrections based on QM protomer and calculations increase the correlation between predicted and experimental distribution coefficients, for all methods used. Unfortunately, these corrections are overly hydrophilic, and fail to account for additional effects such as aggregation, water dragging and the presence of polar impurities in the apolar phase. We show that, although expensive, QM-NBB free energy calculations offer an accurate and robust method that is superior to standard MM and QM techniques alone.
C1 [Pickard, Frank C.; Koenig, Gerhard; Tofoleanu, Florentina; Lee, Juyong; Simmonett, Andrew C.; Brooks, Bernard R.] NHLBI, Lab Computat Biol, NIH, 5635 Fishers Lane,T-900 Suite, Rockville, MD 20852 USA.
[Koenig, Gerhard] Max Planck Inst Kohlenforsch, D-45470 Mulheim, Germany.
[Shao, Yihan] Univ Oklahoma, Dept Chem & Biochem, Norman, OK 73019 USA.
[Ponder, Jay W.] Washington Univ, Dept Chem, St Louis, MO 63130 USA.
RP Pickard, FC (reprint author), NHLBI, Lab Computat Biol, NIH, 5635 Fishers Lane,T-900 Suite, Rockville, MD 20852 USA.
EM frank.pickard@nih.gov
OI Pickard, Frank/0000-0002-9608-3466
FU National Heart, Lung and Blood Institute of the National Institutes of
Health
FX This work was supported by the intramural research program of the
National Heart, Lung and Blood Institute of the National Institutes of
Health and utilized the high-performance computational capabilities of
the LoBoS and Biowulf Linux clusters at the National Institutes of
Health. (http://www.lobos.nih.gov and http://biowulf.nih.gov)
NR 80
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PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0920-654X
EI 1573-4951
J9 J COMPUT AID MOL DES
JI J. Comput.-Aided Mol. Des.
PD NOV
PY 2016
VL 30
IS 11
SI SI
BP 1087
EP 1100
DI 10.1007/s10822-016-9955-7
PN 1
PG 14
WC Biochemistry & Molecular Biology; Biophysics; Computer Science,
Interdisciplinary Applications
SC Biochemistry & Molecular Biology; Biophysics; Computer Science
GA EH0MU
UT WOS:000391459000014
PM 27646286
ER
PT J
AU Jones, MR
Brooks, BR
Wilson, AK
AF Jones, Michael R.
Brooks, Bernard R.
Wilson, Angela K.
TI Partition coefficients for the SAMPL5 challenge using transfer free
energies
SO JOURNAL OF COMPUTER-AIDED MOLECULAR DESIGN
LA English
DT Article
DE SAMPL; Distribution coefficient; Partition coefficient; Water;
Cyclohexane; SMD; B3PW91; DFT; Solvation
ID CONSISTENT BASIS-SETS; DENSITY-FUNCTIONAL THEORY; SOLVATION
FREE-ENERGIES; CORRELATED MOLECULAR CALCULATIONS; GAUSSIAN-BASIS SETS;
HYDRATION FREE-ENERGIES; WATER CLUSTERS; NONCOVALENT INTERACTIONS;
THERMOCHEMICAL KINETICS; BLIND PREDICTION
AB SAMPL challenges (Mobley et al. in J Comput Aided Mol Des 28:135-150, 2014; Skillman in J Comput Aided Mol Des 26:473-474, 2012; Geballe in J Comput Aided Mol Des 24:259-279, 2010; Guthrie in J Phys Chem B 113:4501-4507, 2009) provide excellent opportunities to assess theoretical approaches on new data sets with a goal of gaining greater insight towards protein and ligand modeling. In the SAMPL5 experiment, cyclohexane-water partition coefficients were determined using a vertical solvation scheme in conjunction with the SMD continuum solvent model. Several DFT functionals partnered with correlation consistent basis sets were evaluated for the prediction of the partition coefficients. The approach chosen for the competition, a B3PW91 vertical solvation scheme, yields a mean absolute deviation of 1.9 logP units and performs well at estimating the correct hydrophilicity and hydrophobicity for the full SAMPL5 molecule set.
C1 [Jones, Michael R.; Wilson, Angela K.] Michigan State Univ, Dept Chem, 578 S Shaw Ln, E Lansing, MI 48824 USA.
[Jones, Michael R.; Brooks, Bernard R.] NHLBI, Lab Computat Biol, 5635 Fishers Lane,T-900 Suite, Rockville, MD 20852 USA.
RP Wilson, AK (reprint author), Michigan State Univ, Dept Chem, 578 S Shaw Ln, E Lansing, MI 48824 USA.
EM wilson@chemistry.msu.edu
FU Intramural Research Program of the NIH, NHLBI
FX This research was supported in part by the Intramural Research Program
of the NIH, NHLBI. During the beginning of the SAMPL5 competition, AKW
and MRJ were at the University of North Texas, where the calculations
were done. Thus, the authors gratefully acknowledge Research Computing
Services at the University of North Texas for computational resources.
The authors thank Frank C. Pickard IV and Yihan Shao for their comments
on the manuscript.
NR 57
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U1 4
U2 4
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0920-654X
EI 1573-4951
J9 J COMPUT AID MOL DES
JI J. Comput.-Aided Mol. Des.
PD NOV
PY 2016
VL 30
IS 11
SI SI
BP 1129
EP 1138
DI 10.1007/s10822-016-9964-6
PN 1
PG 10
WC Biochemistry & Molecular Biology; Biophysics; Computer Science,
Interdisciplinary Applications
SC Biochemistry & Molecular Biology; Biophysics; Computer Science
GA EH0MU
UT WOS:000391459000017
PM 27646287
ER
PT J
AU McMahon, B
Aflaki, E
Sidransky, E
AF McMahon, Benjamin
Aflaki, Elma
Sidransky, Ellen
TI Chaperoning glucocerebrosidase: a therapeutic strategy for both Gaucher
disease and Parkinsonism
SO NEURAL REGENERATION RESEARCH
LA English
DT Editorial Material
ID ALPHA-SYNUCLEIN; NEURONS
C1 [McMahon, Benjamin; Aflaki, Elma; Sidransky, Ellen] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA.
RP Sidransky, E (reprint author), NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA.
EM sidranse@mail.nih.gov
FU National Human Genome Research Institute; National Institutes of Health
FX This work was supported by the Intramural Research Programs of the
National Human Genome Research Institute and the National Institutes of
Health.
NR 13
TC 0
Z9 0
U1 1
U2 1
PU MEDKNOW PUBLICATIONS & MEDIA PVT LTD
PI MUMBAI
PA B-9, KANARA BUSINESS CENTRE, OFF LINK RD, GHAKTOPAR-E, MUMBAI, 400075,
INDIA
SN 1673-5374
EI 1876-7958
J9 NEURAL REGEN RES
JI Neural Regen. Res.
PD NOV
PY 2016
VL 11
IS 11
BP 1760
EP 1761
DI 10.4103/1673-5374.194717
PG 2
WC Cell Biology; Neurosciences
SC Cell Biology; Neurosciences & Neurology
GA EH2DW
UT WOS:000391578600018
PM 28123414
ER
PT J
AU Goey, AKL
Sissung, TM
Peer, CJ
Figg, WD
AF Goey, Andrew K. L.
Sissung, Tristan M.
Peer, Cody J.
Figg, William D.
TI Pharmacogenomics and histone deacetylase inhibitors
SO PHARMACOGENOMICS
LA English
DT Review
DE belinostat; HDAC inhibitors; panobinostat; pharmacogenomics; romidepsin;
UGT1A1; valproic acid; vorinostat
ID GLUCURONOSYLTRANSFERASE 1A1 PROMOTER; VALPROIC ACID PHARMACOKINETICS;
IRINOTECAN-INDUCED NEUTROPENIA; CHINESE EPILEPSY PATIENTS;
UGT1A1-ASTERISK-28 GENOTYPE; PANOBINOSTAT LBH589; FUNCTIONAL IMPACT;
GLUCURONIDATION; POLYMORPHISMS; UGT2B7
AB The histone deacetylase inhibitor valproic acid (VPA) has been used for many decades in neurology and psychiatry. The more recent introduction of the histone deacetylase inhibitors (HDIs) belinostat, romidepsin and vorinostat for treatment of hematological malignancies indicates the increasing popularity of these agents. Belinostat, romidepsin and vorinostat are metabolized or transported by polymorphic enzymes or drug transporters. Thus, genotype-directed dosing could improve pharmacotherapy by reducing the risk of toxicities or preventing suboptimal treatment. This review provides an overview of clinical studies on the effects of polymorphisms on the pharmacokinetics, efficacy or toxicities of HDIs including belinostat, romidepsin, vorinostat, panobinostat, VPA and a number of novel compounds currently being tested in Phase I and II trials. Although pharmacogenomic studies for HDIs are scarce, available data indicate that therapy with belinostat (UGT1A1), romidepsin (ABCB1), vorinostat (UGT2B17) or VPA (UGT1A6) could be optimized by upfront genotyping.
C1 [Goey, Andrew K. L.; Sissung, Tristan M.; Peer, Cody J.; Figg, William D.] NCI, Clin Pharmacol Program, NIH, Bethesda, MD 20892 USA.
RP Figg, WD (reprint author), NCI, Clin Pharmacol Program, NIH, Bethesda, MD 20892 USA.
EM figgw@helix.nih.gov
NR 48
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U1 2
U2 2
PU FUTURE MEDICINE LTD
PI LONDON
PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3
1QB, ENGLAND
SN 1462-2416
EI 1744-8042
J9 PHARMACOGENOMICS
JI Pharmacogenomics
PD NOV
PY 2016
VL 17
IS 16
BP 1807
EP 1815
DI 10.2217/pgs-2016-0113
PG 9
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA EH6EL
UT WOS:000391865500008
PM 27767376
ER
PT J
AU Podolanczukt, AJ
Oelsner, EC
Barr, RG
Hoffman, EA
Armstrong, HF
Austin, JHM
Basner, RC
Bartels, MN
Christie, JD
Enright, PL
Gochuico, BR
Stukovsky, KH
Kaufman, JD
Nath, PH
Newell, JD
Palmer, SM
Rabinowitz, D
Raghu, G
Sell, JL
Sieren, J
Sonavane, SK
Tracy, RP
Watts, JR
Williams, K
Kawut, SM
Lederer, DJ
AF Podolanczukt, Anna J.
Oelsner, Elizabeth C.
Barr, R. Graham
Hoffman, Eric A.
Armstrong, Hilary F.
Austin, John H. M.
Basner, Robert C.
Bartels, Matthew N.
Christie, Jason D.
Enright, Paul L.
Gochuico, Bernadette R.
Stukovsky, Karen Hinckley
Kaufman, Joel D.
Nath, P. Hrudaya
Newell, John D., Jr.
Palmer, Scott M.
Rabinowitz, Dan
Raghu, Ganesh
Sell, Jessica L.
Sieren, Jered
Sonavane, Sushil K.
Tracy, Russell P.
Watts, Jubal R.
Williams, Kayleen
Kawut, Steven M.
Lederer, David J.
TI High attenuation areas on chest computed tomography in
community-dwelling adults: the MESA study
SO EUROPEAN RESPIRATORY JOURNAL
LA English
DT Article
ID IDIOPATHIC PULMONARY-FIBROSIS; INTERSTITIAL LUNG ABNORMALITIES;
C-REACTIVE PROTEIN; AIR-FLOW OBSTRUCTION; ATHEROSCLEROSIS MESA; CARDIAC
CT; DISEASE; EMPHYSEMA; INTERLEUKIN-6; ASSOCIATION
AB Evidence suggests that lung injury, inflammation and extracellular matrix remodelling precede lung fibrosis in interstitial lung disease (ILD). We examined whether a quantitative measure of increased lung attenuation on computed tomography (CT) detects lung injury, inflammation and extracellular matrix remodelling in community-dwelling adults sampled without regard to respiratory symptoms or smoking.
We measured high attenuation areas (HAA; percentage of lung voxels between -600 and -250 Hounsfield Units) on cardiac CT scans of adults enrolled in the Multi-Ethnic Study of Atherosclerosis.
HAA was associated with higher serum matrix metalloproteinase-7 (mean adjusted difference 6.3% per HAA doubling, 95% CI 1.3-11.5), higher interleukin-6 (mean adjusted difference 8.8%, 95% CI 4.8-13.0), lower forced vital capacity (FVC) (mean adjusted difference -82 mL, 95% CI -119--44), lower 6-min walk distance (mean adjusted difference -40 m, 95% CI -1--80), higher odds of interstitial lung abnormalities at 9.5 years (adjusted OR 1.95, 95% CI 1.43-2.65), and higher all cause-mortality rate over 12.2 years (HR 1.58, 95% CI 1.39-1.79).
High attenuation areas are associated with biomarkers of inflammation and extracellular matrix remodelling, reduced lung function, interstitial lung abnormalities, and a higher risk of death among community-dwelling adults.
C1 [Podolanczukt, Anna J.; Oelsner, Elizabeth C.; Barr, R. Graham; Basner, Robert C.; Sell, Jessica L.; Lederer, David J.] Columbia Univ, Dept Med, Med Ctr, New York, NY USA.
[Barr, R. Graham; Armstrong, Hilary F.; Lederer, David J.] Columbia Univ, Med Ctr, Dept Epidemiol, New York, NY USA.
[Hoffman, Eric A.; Newell, John D., Jr.] Univ Iowa, Dept Radiol, Carver Coll Med, Iowa City, IA 52242 USA.
[Hoffman, Eric A.; Newell, John D., Jr.] Univ Iowa, Dept Med, Carver Coll Med, Iowa City, IA 52242 USA.
[Hoffman, Eric A.; Newell, John D., Jr.] Univ Iowa, Dept Biomed Engn, Carver Coll Med, Iowa City, IA 52242 USA.
[Austin, John H. M.] Columbia Univ, Med Ctr, Dept Radiol, New York, NY USA.
[Bartels, Matthew N.] Montefiore Med Ctr, Albert Einstein Coll Med, Dept Rehabil Med, Bronx, NY 10467 USA.
[Christie, Jason D.] Univ Penn, Dept Med, Philadelphia, PA 19104 USA.
[Christie, Jason D.] Univ Penn, Ctr Translat Lung Biol, Philadelphia, PA 19104 USA.
[Enright, Paul L.] Univ Arizona, Dept Epidemiol, Tucson, AZ USA.
[Gochuico, Bernadette R.] NHGRI, Bethesda, MD 20892 USA.
[Stukovsky, Karen Hinckley] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
[Kaufman, Joel D.; Raghu, Ganesh; Williams, Kayleen] Univ Washington, Dept Med, Seattle, WA USA.
[Nath, P. Hrudaya; Sonavane, Sushil K.; Watts, Jubal R.] Univ Alabama, Dept Radiol, South Birmingham, AL USA.
[Palmer, Scott M.] Duke Univ, Duke Clin Res Inst, Durham, NC USA.
[Rabinowitz, Dan] Columbia Univ, Dept Stat, New York, NY USA.
[Sieren, Jered] VIDA Diagnost Inc, Coralville, IA USA.
[Tracy, Russell P.] Univ Vermont, Dept Pathol, Colchester, VT USA.
[Kawut, Steven M.] Univ Penn, Dept Med, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Kawut, Steven M.] Univ Penn, Ctr Clin Epidemiol & Biostat, Perelman Sch Med, Philadelphia, PA 19104 USA.
Columbia Univ, Med Ctr, Med & Epidemiol, New York, NY 10032 USA.
RP Lederer, DJ (reprint author), Columbia Univ, Med Ctr, Med & Epidemiol, 161 Ft Washington Ave,Room 3-321A, New York, NY 10032 USA.
EM davidlederer@columbia.edu
OI Kaufman, Joel/0000-0003-4174-9037; Watts, Jubal/0000-0002-9006-1637
FU National Heart, Lung, and Blood Institute [R01 HL103676, R01 HL077612,
R01 HL114626, RC1-100543, R01-HL093081, N01-HC-95159, N01-HC-95160,
N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165,
N01-HC-95166, N01-HC-95167, N01-HC-95168, N01-HC-95169, T32 HL105323];
NCRR/NCATS [UL1-TR-000040, UL1-RR-025005]; Pulmonary Fibrosis
Foundation; FundRef
FX This research was supported by grants and contracts R01 HL103676, R01
HL077612, R01 HL114626, RC1-100543 and R01-HL093081, N01-HC-95159,
N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164,
N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168, N01-HC-95169,
and T32 HL105323 from the National Heart, Lung, and Blood Institute, and
by grants UL1-TR-000040 and UL1-RR-025005 from NCRR/NCATS. This project
was funded in part by the Pulmonary Fibrosis Foundation. Funding
information for this manuscript has been deposited with FundRef.
NR 55
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U1 0
U2 0
PU EUROPEAN RESPIRATORY SOC JOURNALS LTD
PI SHEFFIELD
PA 442 GLOSSOP RD, SHEFFIELD S10 2PX, ENGLAND
SN 0903-1936
EI 1399-3003
J9 EUR RESPIR J
JI Eur. Resp. J.
PD NOV
PY 2016
VL 48
IS 5
BP 1442
EP 1452
DI 10.1183/13993003.00129-2016
PG 11
WC Respiratory System
SC Respiratory System
GA EG3VW
UT WOS:000390973800023
PM 27471206
ER
PT J
AU Lamb, AE
Biesecker, BB
Umstead, KL
Muratori, M
Biesecker, LG
Erby, LH
AF Lamb, Amanda E.
Biesecker, Barbara B.
Umstead, Kendall L.
Muratori, Michelle
Biesecker, Leslie G.
Erby, Lori H.
TI Family functioning mediates adaptation in caregivers of individuals with
Rett syndrome
SO PATIENT EDUCATION AND COUNSELING
LA English
DT Article
DE Adaptation; Family functioning; Rett syndrome; Coping; Self-efficacy;
Caregiver; Neurodevelopmental disorder
ID AUTISM SPECTRUM DISORDER; SICKLE-CELL-DISEASE; PSYCHOLOGICAL ADJUSTMENT;
CYSTIC-FIBROSIS; SELF-EFFICACY; MENTAL-HEALTH; CHILDREN; MOTHERS;
STRESS; PARENTS
AB Objective: The objective of this study was to investigate factors related to family functioning and adaptation in caregivers of individuals with Rett syndrome (RS).
Methods: A cross-sectional quantitative survey explored the relationships between demographics, parental self-efficacy, coping methods, family functioning and adaptation. A forward-backward, step-wise model selection procedure was used to evaluate variables associated with both family functioning and adaptation. Analyses also explored family functioning as a mediator of the relationship between other variables and adaptation.
Results: Bivariate analyses (N = 400) revealed that greater parental self-efficacy, a greater proportion of problem-focused coping, and a lesser proportion of emotion-focused coping were associated with more effective family functioning. In addition, these key variables were significantly associated with greater adaptation, as was family functioning, while controlling for confounders. Finally, regression analyses suggest family functioning as a mediator of the relationships between three variables (parental self-efficacy, problem-focused coping, and emotion-focused coping) with adaptation.
Conclusion: This study demonstrates the potentially predictive roles of expectations and coping methods and the mediator role of family functioning in adaptation among caregivers of individuals with RS, a chronic developmental disorder.
Practice implications: A potential target for intervention is strengthening of caregiver competence in the parenting role to enhance caregiver adaptation. Published by Elsevier Ireland Ltd.
C1 [Lamb, Amanda E.; Biesecker, Barbara B.; Umstead, Kendall L.; Erby, Lori H.] NHGRI, Social & Behav Res Branch, NIH, 31 Ctr Dr,Rm B1B36, Bethesda, MD 20814 USA.
[Lamb, Amanda E.; Biesecker, Barbara B.; Muratori, Michelle; Erby, Lori H.] Johns Hopkins Bloomberg Sch Publ Hlth, Hlth Behav & Soc, Baltimore, MD 21205 USA.
[Biesecker, Barbara B.; Biesecker, Leslie G.] NHGRI, Med Genom & Metab Genet Branch, NIH, Bethesda, MD 20814 USA.
[Biesecker, Barbara B.; Muratori, Michelle] Johns Hopkins Ctr Talented Youth, Baltimore, MD USA.
RP Biesecker, BB (reprint author), NHGRI, Social & Behav Res Branch, NIH, 31 Ctr Dr,Rm B1B36, Bethesda, MD 20814 USA.
EM barbarab@mail.nih.gov
FU Intramural Research Program of the National Human Genome Research
Institute, National Institutes of Health
FX This research was supported by the Intramural Research Program of the
National Human Genome Research Institute, National Institutes of Health.
NR 39
TC 0
Z9 0
U1 5
U2 5
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0738-3991
J9 PATIENT EDUC COUNS
JI Patient Educ. Couns.
PD NOV
PY 2016
VL 99
IS 11
BP 1873
EP 1879
DI 10.1016/j.pec.2016.06.018
PG 7
WC Public, Environmental & Occupational Health; Social Sciences,
Interdisciplinary
SC Public, Environmental & Occupational Health; Social Sciences - Other
Topics
GA EG7JC
UT WOS:000391222100018
PM 27373960
ER
PT J
AU Singhal, A
Simmons, M
Lu, ZY
AF Singhal, Ayush
Simmons, Michael
Lu, Zhiyong
TI Text Mining Genotype-Phenotype Relationships from Biomedical Literature
for Database Curation and Precision Medicine
SO PLOS COMPUTATIONAL BIOLOGY
LA English
DT Article
ID MANUAL CURATION; GENETIC-VARIANTS; MUTATION; DISEASE; IMPACT;
IDENTIFICATION; NORMALIZATION; EXTRACTION; SEQUENCES; GENOMES
AB The practice of precision medicine will ultimately require databases of genes and mutations for healthcare providers to reference in order to understand the clinical implications of each patient's genetic makeup. Although the highest quality databases require manual curation, text mining tools can facilitate the curation process, increasing accuracy, coverage, and productivity. However, to date there are no available text mining tools that offer high-accuracy performance for extracting such triplets from biomedical literature. In this paper we propose a high-performance machine learning approach to automate the extraction of disease-gene-variant triplets from biomedical literature. Our approach is unique because we identify the genes and protein products associated with each mutation from not just the local text content, but from a global context as well (from the Internet and from all literature in PubMed). Our approach also incorporates protein sequence validation and disease association using a novel text-mining-based machine learning approach. We extract disease-gene-variant triplets from all abstracts in PubMed related to a set of ten important diseases (breast cancer, prostate cancer, pancreatic cancer, lung cancer, acute myeloid leukemia, Alzheimer's disease, hemochromatosis, age-related macular degeneration (AMD), diabetes mellitus, and cystic fibrosis). We then evaluate our approach in two ways: (1) a direct comparison with the state of the art using benchmark datasets; (2) a validation study comparing the results of our approach with entries in a popular human-curated database (UniProt) for each of the previously mentioned diseases. In the benchmark comparison, our full approach achieves a 28% improvement in F-1-measure (from 0.62 to 0.79) over the state-of-the-art results. For the validation study with UniProt Knowledgebase (KB), we present a thorough analysis of the results and errors. Across all diseases, our approach returned 272 triplets (disease-gene-variant) that overlapped with entries in UniProt and 5,384 triplets without overlap in UniProt. Analysis of the overlapping triplets and of a stratified sample of the nonoverlapping triplets revealed accuracies of 93% and 80% for the respective categories (cumulative accuracy, 77%). We conclude that our process represents an important and broadly applicable improvement to the state of the art for curation of disease-gene-variant relationships.
C1 [Singhal, Ayush; Simmons, Michael; Lu, Zhiyong] NIH, NCBI, NLM, Bldg 10, Bethesda, MD 20892 USA.
RP Lu, ZY (reprint author), NIH, NCBI, NLM, Bldg 10, Bethesda, MD 20892 USA.
EM zhiyong.lu@nih.gov
OI singhal, ayush/0000-0002-2378-3795
FU NIH Intramural Research Program; National Library of Medicine; NIH
Medical Research Scholars Program; NIH
FX This research was supported by the NIH Intramural Research Program,
National Library of Medicine and the NIH Medical Research Scholars
Program, a public-private partnership supported jointly by the NIH and
generous contributions to the Foundation for the NIH from the Doris Duke
Charitable Foundation, the Howard Hughes Medical Institute, the American
Association for Dental Research, the Colgate-Palmolive Company, and
other private donors. No funds from the Doris Duke Charitable Foundation
were used to support research that used animals. The funders had no role
in study design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 45
TC 0
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U1 6
U2 6
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-734X
EI 1553-7358
J9 PLOS COMPUT BIOL
JI PLoS Comput. Biol.
PD NOV
PY 2016
VL 12
IS 11
AR e1005017
DI 10.1371/journal.pcbi.1005017
PG 19
WC Biochemical Research Methods; Mathematical & Computational Biology
SC Biochemistry & Molecular Biology; Mathematical & Computational Biology
GA EG7MC
UT WOS:000391230900002
PM 27902695
ER
PT J
AU Rid, A
Johansson, MA
Leung, G
Valantine, H
Burchard, EG
Oh, SS
Zimmerman, C
AF Rid, Annette
Johansson, Michael A.
Leung, Gabriel
Valantine, Hannah
Burchard, Esteban G.
Oh, Sam S.
Zimmerman, Cathy
CA PLOS Med Editors
TI Towards Equity in Health: Researchers Take Stock
SO PLOS MEDICINE
LA English
DT Editorial Material
ID DIVERSITY
C1 Publ Lib Sci, San Francisco, CA USA.
[PLOS Med Editors] Publ Lib Sci, Cambridge, England.
[Rid, Annette] Kings Coll London, Dept Global Hlth & Social Med, London, England.
[Johansson, Michael A.] Ctr Dis Control & Prevent, Div Vector Borne Dis, San Juan, PR USA.
[Johansson, Michael A.] TH Chan Sch Publ Hlth, Ctr Communicable Dis Dynam, Boston, MA USA.
[Leung, Gabriel] Univ Hong Kong, Li Ka Shing Fac Med, Hong Kong, Hong Kong, Peoples R China.
[Valantine, Hannah] NIH, Off Director, Bldg 10, Bethesda, MD 20892 USA.
[Valantine, Hannah] NHLBI, Lab Genome Transplantat, NIH, Bldg 10, Bethesda, MD 20892 USA.
[Burchard, Esteban G.] Univ Calif San Francisco, Dept Bioengn & Therapeut Sci, San Francisco, CA 94143 USA.
[Burchard, Esteban G.; Oh, Sam S.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA.
[Zimmerman, Cathy] London Sch Hyg & Trop Med, Dept Global Hlth & Dev, London, England.
RP Rid, A (reprint author), Kings Coll London, Dept Global Hlth & Social Med, London, England.
NR 27
TC 0
Z9 0
U1 1
U2 1
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1549-1676
J9 PLOS MED
JI PLos Med.
PD NOV
PY 2016
VL 13
IS 11
AR e1002186
DI 10.1371/journal.pmed.1002186
PG 8
WC Medicine, General & Internal
SC General & Internal Medicine
GA EG7NE
UT WOS:000391233800022
ER
PT J
AU Gonzalez, FJ
Jiang, CT
Patterson, AD
AF Gonzalez, Frank J.
Jiang, Changtao
Patterson, Andrew D.
TI An Intestinal Microbiota-Farnesoid X Receptor Axis Modulates Metabolic
Disease
SO GASTROENTEROLOGY
LA English
DT Review
DE Bile Acids; Farnesoid X Receptor; Metabolic Disease; Ceramides
ID FATTY LIVER-DISEASE; PLACEBO-CONTROLLED TRIAL; BILE-ACID RECEPTORS;
GROWTH-FACTOR 19; NUCLEAR RECEPTOR; GUT MICROBIOTA; INSULIN-RESISTANCE;
ENTEROHEPATIC CIRCULATION; HEPATOCELLULAR-CARCINOMA; DIABETES-MELLITUS
AB The gut microbiota is associated with metabolic diseases including obesity, insulin resistance, and nonalcoholic fatty liver disease, as shown by correlative studies and by transplant of microbiota from obese humans and mice into germ-free mice. Modification of the microbiota by treatment of high-fat diet (HFD)-fed mice with tempol or antibiotics resulted in decreased adverse metabolic phenotypes. This was owing to lower levels of the genera Lactobacillus and decreased bile salt hydrolase (BSH) activity. The decreased BSH resulted in increased levels of tauro-b-muricholic acid (MCA), a substrate of BSH and a potent farnesoid X receptor (FXR) antagonist. Mice lacking expression of FXR in the intestine were resistant to HFD induced obesity, insulin resistance, and nonalcoholic fatty liver disease, thus confirming that intestinal FXR is involved in the potentiation of metabolic disease. A potent intestinal FXR antagonist, glycine-b-MCA (Gly-MCA), which is resistant to BSH, was developed, which, when administered to HFD-treated mice, mimics the effect of the altered microbiota on HFD-induced metabolic disease. Gly-MCA had similar effects on genetically obese leptin-deficient mice. The decrease in adverse metabolic phenotype by tempol, antibiotics, and Gly-MCA was caused by decreased serum ceramides. Mice lacking FXR in the intestine also have lower serum ceramide levels, and are resistant to HFD-induced metabolic disease, and this was reversed by injection of C16:0 ceramide. In mouse ileum, because of the presence of endogenous FXR agonists produced in the liver, FXR target genes involved in ceramide synthesis are activated and when Gly-MCA is administered they are repressed, which likely accounts for the decrease in serum ceramides. These studies show that ceramides produced in the ileum under control of FXR influence metabolic diseases.
C1 [Gonzalez, Frank J.] NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Jiang, Changtao] Peking Univ, Sch Basic Med Sci, Dept Physiol & Pathophysiol, Beijing 100191, Peoples R China.
[Patterson, Andrew D.] Penn State Univ, Dept Vet & Biomed Sci, University Pk, PA 16802 USA.
[Patterson, Andrew D.] Penn State Univ, Ctr Mol Toxicol & Carcinogenesis, University Pk, PA 16802 USA.
RP Gonzalez, FJ (reprint author), NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.; Jiang, CT (reprint author), Peking Univ, Sch Basic Med Sci, Dept Physiol & Pathophysiol, Beijing 100191, Peoples R China.
EM gonzalef@mail.nih.gov; jiangchangtao@bjmu.edu.cn
FU Intramural Research Program, Center for Cancer Research, National Cancer
Institute, National Institutes of Health; National Institutes of
Environmental Health Sciences [ES022186]; National Natural Science
Foundation of China [81522007, 81470554]
FX This work was supported by the Intramural Research Program, Center for
Cancer Research, National Cancer Institute, National Institutes of
Health (F.J.G.); the National Institutes of Environmental Health
Sciences (ES022186 to A.D.P.); and by the National Natural Science
Foundation of China (81522007 and 81470554 to C.J.).
NR 137
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U1 11
U2 11
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0016-5085
EI 1528-0012
J9 GASTROENTEROLOGY
JI Gastroenterology
PD NOV
PY 2016
VL 151
IS 5
BP 845
EP 859
DI 10.1053/j.gastro.2016.08.057
PG 15
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA EG3OM
UT WOS:000390954600025
PM 27639801
ER
PT J
AU Bosetti, F
Galis, ZS
Bynoe, MS
Charette, M
Cipolla, MJ
del Zoppo, GJ
Gould, D
Hatsukami, TS
Jones, TLZ
Koenig, JI
Lutty, GA
Maric-Bilkan, C
Stevens, T
Tolunay, HE
Koroshetz, W
AF Bosetti, Francesca
Galis, Zorina S.
Bynoe, Margaret S.
Charette, Marc
Cipolla, Marilyn J.
del Zoppo, Gregory J.
Gould, Douglas
Hatsukami, Thomas S.
Jones, Teresa L. Z.
Koenig, James I.
Lutty, Gerard A.
Maric-Bilkan, Christine
Stevens, Troy
Tolunay, H. Eser
Koroshetz, Walter
CA Small Blood Vessels Big Hlth
TI "Small Blood Vessels: Big Health Problems?": Scientific Recommendations
of the National Institutes of Health Workshop
SO JOURNAL OF THE AMERICAN HEART ASSOCIATION
LA English
DT Article
DE endothelium; hypertension; imaging; ischemia; microcirculation;
remodeling
ID VASCULAR COGNITIVE IMPAIRMENT; PHENOTYPIC HETEROGENEITY; HYPERTENSION
MECHANISMS; COLLATERAL CIRCULATION; RANDOMIZED-TRIALS; VITAMIN-E;
DISEASE; BRAIN; STROKE; DEMENTIA
C1 [Bosetti, Francesca; Koenig, James I.; Koroshetz, Walter] NINDS, NIH, 6001 Execut Blvd,Rm 2115, Bethesda, MD 20892 USA.
[Jones, Teresa L. Z.] NIDDK, NIH, Bethesda, MD 20892 USA.
[Galis, Zorina S.; Charette, Marc; Maric-Bilkan, Christine; Tolunay, H. Eser] NHLBI, NIH, Bldg 10, Bethesda, MD 20892 USA.
[Bynoe, Margaret S.] Cornell Univ, Ithaca, NY USA.
[Cipolla, Marilyn J.] Univ Vermont, Burlington, VT USA.
[del Zoppo, Gregory J.; Hatsukami, Thomas S.] Univ Washington, Seattle, WA 98195 USA.
[Gould, Douglas] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Lutty, Gerard A.] Johns Hopkins Univ, Baltimore, MD USA.
[Stevens, Troy] Univ S Alabama, Mobile, AL USA.
RP Bosetti, F (reprint author), NINDS, NIH, 6001 Execut Blvd,Rm 2115, Bethesda, MD 20892 USA.
EM frances@ninds.nih.gov
FU National Institute of Neurological Disorders and Stroke; National Heart,
Lung and Blood Institute; National Eye Institute; National Institutes of
Health Office of Disease Prevention; Office of Research on Women's
Health; Microcirculatory Society
FX The workshop was supported by National Institute of Neurological
Disorders and Stroke, National Heart, Lung and Blood Institute, National
Eye Institute, National Institutes of Health Office of Disease
Prevention, and Office of Research on Women's Health. The
dMicrocirculatory Society sponsored 6 Travel Awards to support the
attendance of trainees and junior faculty members.
NR 73
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Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 2047-9980
J9 J AM HEART ASSOC
JI J. Am. Heart Assoc.
PD NOV
PY 2016
VL 5
IS 11
AR e004389
DI 10.1161/JAHA.116.004389
PG 12
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA EG1IU
UT WOS:000390786600044
ER
PT J
AU Hayes, SR
Vargas, AJ
AF Hayes, Shelby R.
Vargas, Ashley J.
TI PROBIOTICS FOR THE PREVENTION OF PEDIATRIC ANTIBIOTIC-ASSOCIATED
DIARRHEA
SO EXPLORE-THE JOURNAL OF SCIENCE AND HEALING
LA English
DT Article
ID CLOSTRIDIUM-DIFFICILE INFECTIONS; TRIALS
C1 [Hayes, Shelby R.; Vargas, Ashley J.] NCI, 6100 Execut Bldv, Rockville, MD 20852 USA.
RP Vargas, AJ (reprint author), NCI, 6100 Execut Bldv, Rockville, MD 20852 USA.
EM ashley.vargas@nih.gov
FU Intramural NIH HHS [Z99 OD999999]
NR 18
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Z9 0
U1 3
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1550-8307
EI 1878-7541
J9 EXPLORE-NY
JI Explore-J Sci. Heal.
PD NOV-DEC
PY 2016
VL 12
IS 6
BP 463
EP 466
PG 4
WC Integrative & Complementary Medicine
SC Integrative & Complementary Medicine
GA EF8YW
UT WOS:000390618900014
PM 27688016
ER
PT J
AU Shisler, S
Eiden, RD
Molnar, DS
Schuetze, P
Coles, CD
Huestis, M
Colder, CR
AF Shisler, Shannon
Eiden, Rina D.
Molnar, Danielle S.
Schuetze, Pamela
Coles, Claire D.
Huestis, Marilyn
Colder, Craig R.
TI Effects of fetal tobacco exposure on focused attention in infancy
SO INFANT BEHAVIOR & DEVELOPMENT
LA English
DT Article
DE Prenatal tobacco exposure; Focused attention; Behavioral reactivity;
Infants
ID EMOTION REGULATION; PRENATAL SMOKING; VISUAL-ATTENTION; NORMATIVE DATA;
RELIABILITY; EXPLORATION; METABOLITES; MECONIUM; ADHD
AB This study examined the association between fetal tobacco exposure (FTE) and focused attention at 9 months of child age, and the role of child sex and infant behavioral reactivity as potential moderators of this association. Data were obtained from 203 mothers and their infants (105 fetally exposed and 98 non-exposed) on infant focused attention and behavioral reactivity to a frustration task. FTE was ascertained via nicotine metabolites in infant meconium, reflecting primarily third trimester fetal exposure. Results demonstrated a main effect of FTE on focused attention, such that exposed infants exhibited lower levels of focused attention than non-exposed infants. Behavioral reactivity, but not infant sex, moderated the relationship between FTE and focused attention, such that exposed infants who were highly reactive to frustration had the lowest levels of focused attention. Results suggest that smoking interventions, even in the third trimester, may have a positive impact on attentional outcomes for infants. (C) 2016 Elsevier Inc. All rights reserved.
C1 [Shisler, Shannon; Eiden, Rina D.; Molnar, Danielle S.] SUNY Buffalo, Res Inst Addict, 1021 Main St, Buffalo, NY 14203 USA.
[Schuetze, Pamela] SUNY Coll Buffalo, Dept Psychol, 1300 Elmwood Ave, Buffalo, NY 14222 USA.
[Coles, Claire D.] Emory Univ, Psychiat & Behav Sci, Pediat, 201 Dowman Dr, Atlanta, GA 30322 USA.
[Huestis, Marilyn] NIDA, Chem & Drug Metab, IRP, NIH,Biomed Res Ctr, Suite 200,Room 05A-721,251 Bayview Blvd, Baltimore, MD 21224 USA.
[Colder, Craig R.] SUNY Buffalo, Dept Psychol, 227 Pk Hall, Buffalo, NY 14260 USA.
RP Shisler, S (reprint author), SUNY Buffalo, Res Inst Addict, 1021 Main St, Buffalo, NY 14203 USA.
EM sshisler@ria.buffalo.edu; eiden@ria.buffalo.edu;
dmolnar@ria.buffalo.edu; schuetp@buffalostate.edu; ccoles@emory.edu;
marilyn.huestis@gmail.com; ccolder@buffalo.edu
FU National Institute on Drug Abuse [R01DA019632]
FX The authors thank the families who participated in this study and the
research staff responsible for data collection. Special thanks to Dr.
Amol Lele for collaboration on data collection at Women and Children's
Hospital of Buffalo. The study was supported by Award #R01DA019632 from
the National Institute on Drug Abuse.
NR 41
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U1 1
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0163-6383
EI 1879-0453
J9 INFANT BEHAV DEV
JI Infant Behav. Dev.
PD NOV
PY 2016
VL 45
BP 1
EP 10
DI 10.1016/j.infbeh.2016.07.008
PN A
PG 10
WC Psychology, Developmental
SC Psychology
GA EG1XJ
UT WOS:000390827400001
PM 27543942
ER
PT J
AU Johns, LE
Ferguson, KK
Meeker, JD
AF Johns, Lauren E.
Ferguson, Kelly K.
Meeker, John D.
TI Relationships Between Urinary Phthalate Metabolite and Bisphenol A
Concentrations and Vitamin D Levels in US Adults: National Health and
Nutrition Examination Survey (NHANES), 2005-2010
SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
LA English
DT Article
ID ENDOCRINE DISRUPTING CHEMICALS; EXPOSURE; POPULATION; EXPRESSION;
ENZYMES; MODELS; SYSTEM; GENES; WOMEN; MEN
AB Context: Recent research suggests that environmental exposure to endocrine-disrupting chemicals may alter circulating 25-hydroxyvitamin D [25(OH)D] levels in humans. To date, no studies have assessed the associations between phthalates and bisphenol A (BPA) and total 25(OH)D in the U.S. general population.
Objective: To explore relationships between urinary concentrations of 11 phthalate metabolites and BPA and serum total 25(OH)D in a representative sample of U.S. adults.
Design: A cross-sectional study.
Setting: U.S. National Health and Nutrition Examination Survey, 2005-2010.
Patients or Other Participants: U.S. general adult population (aged ce20 years).
Interventions: None
Main Outcome Measures: Serum total 25(OH)D measured by liquid chromatography-tandem mass spectrometry.
Results: Metabolites of di(2-ethylhexyl) phthalate (DEHP) were consistently inversely associated with total 25(OH)D in the overall study population and in gender-stratified models. In the overall population, we detected a significant inverse relationship for the molar sum of DEHP metabolites (IDEHP), where an interquartile range increase in IDEHP was associated with a 1.90% decrease (95% confidence interval [CI], -3.64, -0.17) in total 25(OH)D. A positive association was detected for monoethyl phthalate. For BPA, we found a statistically significant inverse relationship in women, but not in men. In women, an interquartile range increase in urinary BPA was associated with a 3.71% decrease (95% CI, -6.41, -1.02) in total 25(OH)D.
Conclusions: Overall, our results provide suggestive evidence that environmental exposure to phthalates and BPA may alter circulating levels of total 25(OH)D in adults. Future human and animal studies are required to resolvethe direction, temporality, and impact of these relationships.
C1 [Johns, Lauren E.; Ferguson, Kelly K.; Meeker, John D.] Univ Michigan, Sch Publ Hlth, Dept Environm Hlth Sci, Ann Arbor, MI 48109 USA.
[Ferguson, Kelly K.] Natl Inst Environm Hlth Sci, Epidemiol Branch, Res Triangle Pk, NC 27709 USA.
RP Meeker, JD (reprint author), Dept Environm Hlth Sci, 1835 SPH 1,1415 Washington Hts, Ann Arbor, MI 48109 USA.
EM meekerj@umich.edu
OI Ferguson, Kelly/0000-0001-8467-3250
FU Intramural Research Program of the National Institutes of Health,
National Institute of Environmental Health Sciences; National Institute
of Environmental Health Sciences, National Institutes of Health
[R01ES018872, P42ES017198, P50ES026049, P01ES0228544, T32ES007062]
FX This research was supported in part by the Intramural Research Program
of the National Institutes of Health, National Institute of
Environmental Health Sciences. Funding was also provided by the National
Institute of Environmental Health Sciences, National Institutes of
Health (Grants R01ES018872, P42ES017198, P50ES026049, P01ES0228544, and
T32ES007062).
NR 43
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U1 6
U2 6
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0021-972X
EI 1945-7197
J9 J CLIN ENDOCR METAB
JI J. Clin. Endocrinol. Metab.
PD NOV
PY 2016
VL 101
IS 11
BP 4062
EP 4069
DI 10.1210/jc.2016-2134
PG 8
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA EG3MK
UT WOS:000390948600022
PM 27648964
ER
PT J
AU Song, IS
Han, K
Park, YM
Ji, S
Jun, SH
Ryu, JJ
Park, JB
AF Song, In-Seok
Han, Kyungdo
Park, Yong-Moon
Ji, Suk
Jun, Sang Ho
Ryu, Jae-Jun
Park, Jun-Beom
TI Severe Periodontitis Is Associated with Insulin Resistance in
Non-abdominal Obese Adults
SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
LA English
DT Article
ID NUTRITION EXAMINATION SURVEY; NORMAL GLUCOSE-TOLERANCE; KOREA
NATIONAL-HEALTH; BETA-CELL FUNCTION; METABOLICALLY OBESE;
DIABETES-MELLITUS; DISEASE; POPULATION; RISK; INFECTIONS
AB Context: We hypothesized that insulin resistance, even with normal body weight (body mass index or waist circumference), can aggravate periodontitis severity.
Objective: We investigated the associations between diabetes, insulin resistance, and severe periodontitis.
Design: Among 29 235 total participants, 5690 subjects aged > 30 y who had periodontal disease with community periodontal index (CPI) of 3 or 4 were selected for this study.
Participants: Data were derived from the 2008-2010 Korea National Health and Nutrition Examination Survey.
Results: Patients diagnosed with type 2 diabetes were more likely to have severe periodontitis (CPI 4) compared with patients with normal glucose tolerance or impaired fasting glucose (P.001). Subjects with severe periodontitis had significantly higher prevalence of abdominal obesity, serum triglycerides, and insulin resistance (P values of .012, <.001, and.003, respectively). The odds ratios (ORs) for prevalence of severe periodontitis were significantly increased from normal glucose tolerance and impaired fasting glucose (OR = 1.32; 95% confidence interval, 1.06-1.64) to type 2 diabetes (OR = 1.5; 95% CI, 1.11-2.02), after adjusting for potential confounders (P for trend =.003). The prevalence of severe periodontitis increased significantly with increasing insulin resistance (P for trend =.04) in nondiabetic individuals. Furthermore, insulin-resistant individuals with normal waist circumference showed significantly higher odds of severe periodontitis (OR = 1.47; 95% CI, 1.16-1.87) than did insulin sensitive individuals with normal waist circumference.
Conclusions: Non-abdominally obese subjects with insulin resistance were more likely to have severe periodontitis. Insulin resistance can be considered an independent riskfactor of periodontal disease in normal weight population defined by abdominal obesity.
C1 [Song, In-Seok; Jun, Sang Ho] Korea Univ, Anam Hosp, Dept Oral & Maxillofacial Surg, Seoul 02841, South Korea.
[Han, Kyungdo] Catholic Univ Korea, Coll Med, Dept Biostat, Seoul 06591, South Korea.
[Park, Yong-Moon] NIEHS, Epidemiol Branch, NIH, Res Triangle Pk, NC 27709 USA.
[Ji, Suk] Ajou Univ Hosp, Dept Periodontol, Suwon 16499, South Korea.
[Ryu, Jae-Jun] Korea Univ, Anam Hosp, Dept Prosthodont, 73 Inchon Ro, Seoul 02841, South Korea.
[Park, Jun-Beom] Catholic Univ Korea, Coll Med, Dept Periodont, Seoul 06591, South Korea.
RP Ryu, JJ (reprint author), Korea Univ, Anam Hosp, Dept Prosthodont, 73 Inchon Ro, Seoul 02841, South Korea.; Park, JB (reprint author), Catholic Univ Korea, Coll Med, Seoul St Marys Hosp, Dept Periodont, 222 Banpo Daero, Seoul 06591, South Korea.
EM koprosth@unitel.co.kr; jbassoonis@yahoo.co.kr
NR 40
TC 1
Z9 1
U1 1
U2 1
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0021-972X
EI 1945-7197
J9 J CLIN ENDOCR METAB
JI J. Clin. Endocrinol. Metab.
PD NOV
PY 2016
VL 101
IS 11
BP 4251
EP 4259
DI 10.1210/jc.2016-2061
PG 9
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA EG3MK
UT WOS:000390948600045
PM 27598510
ER
PT J
AU Chaker, L
Baumgartner, C
den Elzen, WPJ
Collet, TH
Ikram, MA
Blum, MR
Dehghan, A
Drechsler, C
Luben, RN
Portegies, MLP
Lervasi, G
Medici, M
Stott, DJ
Dullaart, RP
Ford, I
Bremner, A
Newman, AB
Wanner, C
Sgarbi, JA
Dorr, M
Longstreth, WT
Psaty, BM
Ferrucci, L
Maciel, RMB
Westendorp, RG
Jukema, JW
Ceresini, G
Imaizumi, M
Hofman, A
Bakker, SJL
Franklyn, JA
Khaw, KT
Bauer, DC
Walsh, JP
Razvi, S
Gussekloo, J
Volzke, H
Franco, OH
Cappola, AR
Rodondi, N
Peeters, RP
AF Chaker, Layal
Baumgartner, Christine
den Elzen, Wendy P. J.
Collet, Tinh-Hai
Ikram, M. Arfan
Blum, Manuel R.
Dehghan, Abbas
Drechsler, Christiane
Luben, Robert N.
Portegies, Marileen L. P.
Lervasi, Giorgio
Medici, Marco
Stott, David J.
Dullaart, Robin P.
Ford, Ian
Bremner, Alexandra
Newman, Anne B.
Wanner, Christoph
Sgarbi, Jose A.
Dorr, Marcus
Longstreth, W. T., Jr.
Psaty, Bruce M.
Ferrucci, Luigi
Maciel, Rui M. B.
Westendorp, Rudi G.
Jukema, J. Wouter
Ceresini, Graziano
Imaizumi, Misa
Hofman, Albert
Bakker, Stephan J. L.
Franklyn, Jayne A.
Khaw, Kay-Tee
Bauer, Douglas C.
Walsh, John P.
Razvi, Salman
Gussekloo, Jacobijn
Volzke, Henry
Franco, Oscar H.
Cappola, Anne R.
Rodondi, Nicolas
Peeters, Robin P.
CA Thyroid Studies Collaboration
TI Thyroid Function Within the Reference Range and the Risk of Stroke: An
Individual Participant Data Analysis
SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
LA English
DT Article
ID ISCHEMIC-HEART-DISEASE; SERVICES TASK-FORCE; SUBCLINICAL HYPOTHYROIDISM;
CARDIOVASCULAR RISK; SERUM THYROTROPIN; MYOCARDIAL-INFARCTION;
BLOOD-PRESSURE; OLDER-ADULTS; ALL-CAUSE; DYSFUNCTION
AB Context: The currently applied reference ranges for thyroid function are under debate. Despite evidence that thyroid function within the reference range is related with several cardiovascular disorders, its association with the risk of stroke has not been evaluated previously.
Design and Setting: We identified studies through a systematic literature search and the Thyroid Studies Collaboration, a collaboration of prospective cohort studies. Studies measuring baseline TSH, free T-4, and stroke outcomes were included, and we collected individual participant data from each study, including thyroid function measurements and incident all stroke (combined fatal and nonfatal) and fatal stroke. The applied reference range for TSH levels was between 0.45 and 4.49 mIU/L.
Results: We collected individual participant data on 43 598 adults with TSH within the reference range from 17 cohorts, with a median follow-up of 11.6 years (interquartile range 5.1-13.9), including 449 908 person-years. Age- and sex-adjusted pooled hazard ratio for TSH was 0.78 (95% confidence interval [CI] 0.65-0.95 across the reference range of TSH) for all stroke and 0.83 (95% CI 0.62-1.09) for fatal stroke. For the free T4 analyses, the hazard ratio was 1.08 (95% CI 0.99-1.15 per SD increase) for all stroke and 1.10 (95% CI 1.04-1.19) for fatal stroke. This was independent of cardiovascular risk factors including systolic blood pressure, total cholesterol, smoking, and prevalent diabetes.
Conclusion: Higher levels of TSH within the reference range may decrease the risk of stroke, highlighting the need for further research focusing on the clinical consequences associated with differences within the reference range of thyroid function.
C1 [Chaker, Layal; Medici, Marco; Peeters, Robin P.] Erasmus Univ, Med Ctr, Dept Internal Med, NL-3000 DR Rotterdam, Netherlands.
[Chaker, Layal; Medici, Marco; Peeters, Robin P.] Erasmus Filed Ctr, Rotterdam Thyroid Ctr, NL-3000 CA Rotterdam, Netherlands.
[Ikram, M. Arfan] Erasmus Filed Ctr, Dept Radiol & Neurol, NL-3000 CA Rotterdam, Netherlands.
[Baumgartner, Christine; Blum, Manuel R.; Rodondi, Nicolas] Univ Bern, Bern Univ Hosp, Inselspital, Dept Gen Internal Med, CH-3010 Bern, Switzerland.
[Collet, Tinh-Hai] Univ Lausanne Hosp, Serv Endocrinol Diabet & Metab, CH-1011 Lausanne, Switzerland.
[den Elzen, Wendy P. J.] Leiden Univ, Med Ctr, Dept Clin Chem & Lab Med, NL-2300 RC Leiden, Netherlands.
[Gussekloo, Jacobijn] Leiden Univ, Med Ctr, Dept Publ Hlth & Primary Care, NL-2300 RC Leiden, Netherlands.
Leiden Univ, Med Ctr, Dept Cardiol, NL-2300 RC Leiden, Netherlands.
[Bauer, Douglas C.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA.
[Bauer, Douglas C.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA.
[Cappola, Anne R.] Univ Penn, Sch Med, Dept Med, Div Endocrinol Diabet & Metab, Philadelphia, PA 19104 USA.
[Hofman, Albert] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Razvi, Salman] Gateshead Hlth Fdn Natl Hlth Serv Mast, Dept Endocrinol, Gateshead SE18 4QH, England.
[Walsh, John P.] Sir Charles Gairdner Hosp, Dept Endocrinol & Diabet, Nedlands, WA 6009, Australia.
[Walsh, John P.] Univ Western Australia, Sch Med & Pharmacol, Crawley, WA 6009, Australia.
[Bremner, Alexandra] Univ Western Australia, Sch Populat Hlth, Crawley, WA 6009, Australia.
[Lervasi, Giorgio] Natl Council Res Inst ot Clin Physiol, I-56124 Pisa, Italy.
[Ford, Ian] Univ Glasgow, Fac Med, Robertson Ctr Biostat, Glasgow G12 8TA, Lanark, Scotland.
[Stott, David J.] Univ Glasgow, Fac Med, Inst Cardiovasc & Med Sci, Glasgow G12 8TA, Lanark, Scotland.
[Newman, Anne B.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15260 USA.
[Dullaart, Robin P.; Bakker, Stephan J. L.] Univ Groningen, Univ Med Ctr Groningen, Dept Internal Med, NL-9700 AB Groningen, Netherlands.
[Drechsler, Christiane; Wanner, Christoph] Univ Hosp Wurzburg, Div Nephrol, Dept Med, D-97070 Wurzburg, Germany.
[Drechsler, Christiane; Wanner, Christoph] Comprehens Heart Failure Ctr, D-97070 Wurzburg, Germany.
[Imaizumi, Misa] Radiat Eftects Res Fdn, Dept Clin Studies, Nagasaki 8508555, Japan.
[Ceresini, Graziano] Univ Parma, Dept Clin & Expt Med, I-143100 Parma, Italy.
[Ferrucci, Luigi] NIA, Baltimore, MD 21225 USA.
[Volzke, Henry] German Ctr Cardiovasc Res, Clin Epidemiol Res, Study Hlth Pomerania, Inst Community Med,Univ Med, D-17187 Greifswald, Germany.
[Dorr, Marcus] German Ctr Cardiovasc Res, Dept Internal Med, D-17187 Greifswald, Germany.
[Dorr, Marcus] German Ctr Cardiovasc Res, Univ Med, D-17187 Greifswald, Germany.
[Longstreth, W. T., Jr.] Univ Washington, Dept Neurol, Seattle, WA 98108 USA.
[Longstreth, W. T., Jr.] Univ Washington, Dept Epidemiol, Seattle, WA 98108 USA.
[Longstreth, W. T., Jr.] Univ Washington, Cardiovasc Hlth Res Unit, Dept Med, Seattle, WA 98108 USA.
[Longstreth, W. T., Jr.] Univ Washington, Cardiovasc Hlth Res Unit, Dept Epidemiol, Seattle, WA 98108 USA.
[Longstreth, W. T., Jr.] Univ Washington, Cardiovasc Hlth Res Unit, Dept Hlth Serv, Seattle, WA 98108 USA.
[Psaty, Bruce M.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA 98101 USA.
[Maciel, Rui M. B.; Franklyn, Jayne A.] Univ Fed Sao Paulo, Dept Med, Div Endocrinol, BR-05150890 Sao Paulo, Brazil.
[Sgarbi, Jose A.] Fau Med Marilia, Div Endocrinol, Marilia, Brazil.
[Luben, Robert N.; Khaw, Kay-Tee] Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge CB2 1TN, England.
[Jukema, J. Wouter] Interuniv Cardiol Inst Netherlands, NL-3508 GA Utrecht, Netherlands.
[Franklyn, Jayne A.] Univ Birmingham, Coll Med & Dent Sci, Sch Clin & Expt Med, Birmingham B15 2TT, W Midlands, England.
[Westendorp, Rudi G.] Univ Copenhagen, Fac Hlth & Med Sci, Dept Publ Hlth, DK-2400 Copenhagen, Denmark.
[Westendorp, Rudi G.] Univ Copenhagen, Fac Hlth & Med Sci, Ctr Hlth Ageing, DK-2400 Copenhagen, Denmark.
RP Peeters, RP (reprint author), Erasmus Univ, Med Ctr, Dept Internal Med, Rotterdam Thyroid Ctr, Room NA28-18,POB 2040, NL-3000 CA Rotterdam, Netherlands.; Peeters, RP (reprint author), Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam Thyroid Ctr, Room NA28-18,POB 2040, NL-3000 CA Rotterdam, Netherlands.
EM r.peeters@erasmusmc.nl
OI Blum, Manuel/0000-0003-4638-775X; Collet, Tinh-Hai/0000-0002-3243-1222
FU Erasmus Medical Center MRACE grant; ZonMW TOP grant [91212044]; Genzyme
B.V.; Swiss National Science Foundation [PBLAP3-145870, P3SMP3-155318,
SNSF 320030-138267, 320030-150025]; Loll LifeCor; Johnson Johnson;
National Institute on Aging [R01AG032317, K24AG042765, AG023629,
N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106, R01-AG028050]; National
Heart, Lung, and Blood Institute [HHSN268 201200036C, HHSN268200800007C,
N01HC55222, N01HC 85079, N01HC85080, N01HC85081, N01HC85082, N01HC8
5083, N01HC285086, HL080295]; National Institute of Neurological
Disorders and Stroke; National Institute of Nursing Research
[R01-NR012459]; Intramural Research Program of the National Institutes
of Health, National Institute on Aging; Research Network of Community
Medicine of the University Medicine Greifswald; German Research
Foundation [DFG Vo 955/12-2]; Japanese Ministry of Health, Labor, and
Welfare; US Department of Energy; Radiation Effects Research Foundation
[A3-13]; Sao Paulo State Research Foundation (Fundacao de Amaparo a
Pesquisa do Estado de Sao Paulo) [6/59737-9]; Dutch Kidney Foundation
[E.033]; University Medical Center Groningen; Dutch Heart Foundation
[2001-005]; National Institutes of Health; National Institute of
Arthritis and Musculoskeletal and Skin Diseases; National Center for
Advancing Translational Sciences; National Institutes of Health Roadmap
for Medical Research [U01 AG027810, U01 AG042124, U01 AG04 2139, U01
AG042140, U01 AG042143, U01 AG042145, U01 AG042168, U01 AR066160, UL1
TR000128]
FX R.P.P. and L.C. are supported by an Erasmus Medical Center MRACE grant
and a ZonMW TOP grant (Grant 91212044). R.P.P. has received lecture and
consultancy-fees from Genzyme B.V. T.-H.C.'s research is supported by
Grants PBLAP3-145870 and P3SMP3-155318 from the Swiss National Science
Foundation. B.M.P. serves on a DSMB for a clinical trial of a device
funded by the manufacturer (Loll LifeCor) and on the Steering Committee
of the Yale Open Data Access Project funded by Johnson & Johnson. The
Thyroid Studies Collaboration is supported by Grants SNSF 320030-138267
and 320030-150025 from the Swiss National Science Foundation (to N.R.).r
Cohort-related funding included the Cardiovascular Health Study
supported by Grants R01AG032317 and K24AG042765 from the National
Institute on Aging; Contracts HHSN268 201200036C, HHSN268200800007C,
N01HC55222, N01HC 85079, N01HC85080, N01HC85081, N01HC85082, N01HC8
5083, and N01HC285086 and Grant HL080295 from the National Heart, Lung,
and Blood Institute, with additional contribution from the National
Institute of Neurological Disorders and Stroke. Additional support was
provided by Grant AG023629 from the National Institute on Aging. A full
list of the principal Cardiovascular Health Study investigators and
institutions can be found at chs-nhlbi.org.r The Health ABC Study was
supported by National Institute on Aging Contracts N01-AG-6-2101,
N01-AG-6-2103, and N01-AG-6-2106; National Institute on Aging Grant
R01-AG028050; and National Institute of Nursing Research Grant
R01-NR012459. This research was supported in part by the Intramural
Research Program of the National Institutes of Health, National
Institute on Aging.r The Study of Health in Pomerania analyses were
funded by the Research Network of Community Medicine of the University
Medicine Greifswald (www.community-medicine.de) and the German Research
Foundation Grant DFG Vo 955/12-2.r The Radiation Effects Research
Foundation (Hiroshima and Nagasaki, Japan) is a public interest
foundation supported by the Japanese Ministry of Health, Labor, and
Welfare and the US Department of Energy. This publication was supported
by Radiation Effects Research Foundation Research Protocol Grant A3-13.r
The Brazilian Thyroid Study was supported by an unrestricted grant from
the Sao Paulo State Research Foundation (Fundacao de Amaparo a Pesquisa
do Estado de Sao Paulo) Grant 6/59737-9 (to R.M.B.M.).r The Dutch Kidney
Foundation supported the infrastructure of the PREVEND program from 1997
to 2003 (Grant E.033). The University Medical Center Groningen supported
the infrastructure from 2003 to 2006. Dade Behring, Ausam, Roche, and
Abbott financed laboratory equipment and reagents by which various
laboratory determinations could be performed. The Dutch Heart Foundation
supported studies on lipid metabolism (Grant 2001-005).r The
Osteoporotic Fractures in Men Study is supported by the National
Institutes of Health. The following institutes provide support: the
National Institute on Aging, the National Institute of Arthritis and
Musculoskeletal and Skin Diseases, the National Center for Advancing
Translational Sciences, and National Institutes of Health Roadmap for
Medical Research under the following grants: U01 AG027810, U01 AG042124,
U01 AG04 2139, U01 AG042140, U01 AG042143, U01 AG042145, U01 AG042168,
U01 AR066160, and UL1 TR000128.
NR 59
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PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0021-972X
EI 1945-7197
J9 J CLIN ENDOCR METAB
JI J. Clin. Endocrinol. Metab.
PD NOV
PY 2016
VL 101
IS 11
BP 4270
EP 4282
DI 10.1210/jc.2016-2255
PG 13
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA EG3MK
UT WOS:000390948600047
PM 27603906
ER
PT J
AU Shmeeda, H
Amitay, Y
Gorin, J
Tzemach, D
Mak, L
Stern, ST
Barenholz, Y
Gabizon, A
AF Shmeeda, Hilary
Amitay, Yasmine
Gorin, Jenny
Tzemach, Dina
Mak, Lidia
Stern, Stephan T.
Barenholz, Yechezkel
Gabizon, Alberto
TI Coencapsulation of alendronate and doxorubicin in pegylated liposomes: a
novel formulation for chemoimmunotherapy of cancer
SO JOURNAL OF DRUG TARGETING
LA English
DT Article
DE Alendronate; chemoimmunotherapy; coencapsulation; pegylated liposomes
ID LIPID-BASED PRODRUG; DELTA T-CELLS; ZOLEDRONIC ACID; BREAST-CANCER;
IN-VIVO; TUMOR-GROWTH; MITOMYCIN-C; BISPHOSPHONATES; THERAPY; ACTIVATION
AB We developed a pegylated liposome formulation of a dissociable salt of a nitrogen-containing bisphosphonate, alendronate (Ald), coencapsulated with the anthracycline, doxorubicin (Dox), a commonly used chemotherapeutic agent. Liposome-encapsulated ammonium Ald generates a gradient driving Dox into liposomes, forming a salt that holds both drugs in the liposome water phase. The resulting formulation (PLAD) allows for a high-loading efficiency of Dox, comparable to that of clinically approved pegylated liposomal doxorubicin sulfate (PLD) and is very stable in plasma stability assays. Cytotoxicity tests indicate greater potency for PLAD compared to PLD. This appears to be related to a synergistic effect of the coencapsulated Ald and Dox. PLAD and PLD differed in in vitro monocyte-induced IL-1 release (greater for PLAD) and complement activation (greater for PLD). A molar ratio Ald/Dox of approximate to 1:1 seems to provide an optimal compromise between loading efficiency of Dox, circulation time and in vivo toxicity of PLAD. In mice, the circulation half-life and tumor uptake of PLAD were comparable to PLD. In the M109R and 4T1 tumor models in immunocompetent mice, PLAD was superior to PLD in the growth inhibition of subcutaneous tumor implants. This new formulation appears to be a promising tool to exploit the antitumor effects of aminobisphosphonates in synergy with chemotherapy.
C1 [Shmeeda, Hilary; Amitay, Yasmine; Gorin, Jenny; Tzemach, Dina; Mak, Lidia; Gabizon, Alberto] Shaare Zedek Med Ctr, Jerusalem, Israel.
[Amitay, Yasmine; Barenholz, Yechezkel; Gabizon, Alberto] Hebrew Univ Jerusalem, Sch Med, Jerusalem, Israel.
[Stern, Stephan T.] NCL, Frederick Natl Lab Canc Res, Frederick, MD USA.
RP Gabizon, A (reprint author), Shaare Zedek Med Ctr, Inst Oncol, POB 3235, IL-91031 Jerusalem, Israel.
EM alberto.gabizon@gmail.com
RI Nanotechnology Characterization Lab, NCL/K-8454-2012
FU Israel Cancer Research Fund; Janssen Pharmaceuticals
FX This work was supported by grants from the Israel Cancer Research Fund,
and Janssen Pharmaceuticals.
NR 42
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PU TAYLOR & FRANCIS LTD
PI ABINGDON
PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND
SN 1061-186X
EI 1029-2330
J9 J DRUG TARGET
JI J. Drug Target.
PD NOV
PY 2016
VL 24
IS 9
SI SI
BP 878
EP 889
DI 10.1080/1061186X.2016.1191081
PG 12
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA EF8RA
UT WOS:000390595600015
PM 27187807
ER
PT J
AU Kendall, GM
Miles, JCH
Rees, D
Wakeford, R
Bunch, KJ
Vincent, TJ
Little, MP
AF Kendall, Gerald M.
Miles, Jon C. H.
Rees, David
Wakeford, Richard
Bunch, Kathryn J.
Vincent, Tim J.
Little, Mark P.
TI Variation with socioeconomic status of indoor radon levels in Great
Britain: The less affluent have less radon
SO JOURNAL OF ENVIRONMENTAL RADIOACTIVITY
LA English
DT Article
DE Radon; Socioeconomic status; Deprivation; Epidemiology
ID CHILDHOOD LEUKEMIA; RESIDENTIAL RADON; LUNG-CANCER; UNITED-STATES;
COLLABORATIVE ANALYSIS; INDIVIDUAL DATA; RISK; RADIATION; EXPOSURE;
INDICATORS
AB We demonstrate a strong correlation between domestic radon levels and socio-economic status (SES) in Great Britain, so that radon levels in homes of people with lower SES are, on average, only about two thirds of those of the more affluent. This trend is apparent using small area measures of SES and also using individual social classes. The reasons for these differences are not known with certainty, but may be connected with greater underpressure in warmer and better-sealed dwellings. There is also a variation of indoor radon levels with the design of the house (detached, terraced, etc.). In part this is probably an effect of SES, but it appears to have other causes as well. Data from other countries are also reviewed, and broadly similar effects seen in the United States for SES, and in other European countries for detached vs other types of housing. Because of correlations with smoking, this tendency for the lower SES groups to experience lower radon levels may underlie the negative association between radon levels and lung cancer rates in a well-known ecological study based on US Counties. Those conducting epidemiological studies of radon should be alert for this effect and control adequately for SES. (C) 2016 Elsevier Ltd. All rights reserved.
C1 [Kendall, Gerald M.] Univ Oxford, Canc Epidemiol Unit, Richard Doll Bldg,Old Rd Campus, Oxford OX3 7LF, England.
[Miles, Jon C. H.; Rees, David] Publ Hlth England, Ctr Radiat Chem & Environm Hazards, Didcot OX11 0RQ, Oxon, England.
[Wakeford, Richard] Univ Manchester, Inst Populat Hlth, Ctr Occupat & Environm Hlth, Ellen Wilkinson Bldg,Oxford Rd, Manchester M13 9PL, Lancs, England.
[Bunch, Kathryn J.] Univ Oxford, Natl Perinatal Epidemiol Unit, Richard Doll Bldg,Old Rd Campus, Oxford OX3 7LF, England.
[Vincent, Tim J.] Univ Oxford, Formerly Childhood Canc Res Grp, New Richards Bldg,Old Rd 12, Oxford OX3 7LF, England.
[Little, Mark P.] NCI, Radiat Epidemiol Branch, DHHS, NIH,Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
RP Kendall, GM (reprint author), Univ Oxford, Canc Epidemiol Unit, Richard Doll Bldg,Old Rd Campus, Oxford OX3 7LF, England.
EM Gerald.Kendall@ceu.ox.ac.uk
OI Wakeford, Richard/0000-0002-2934-0987
FU Intramural Research Program of the National Institutes of Health, the
National Cancer Institute, Division of Cancer Epidemiology and Genetics;
Children with Cancer UK [HTRVVKO]
FX The Childhood Cancer Research Group investigators were supported by
Children with Cancer UK under grant number HTRVVKO. This work was
supported by the Intramural Research Program of the National Institutes
of Health, the National Cancer Institute, Division of Cancer
Epidemiology and Genetics. The authors are grateful for the detailed and
helpful comments of the three referees. RW does consultancy work,
including for the UK Compensation Scheme for Radiation-linked Diseases.
The authors declare that they otherwise have no actual or potential
competing financial interests.
NR 58
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PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0265-931X
EI 1879-1700
J9 J ENVIRON RADIOACTIV
JI J. Environ. Radioact.
PD NOV
PY 2016
VL 164
BP 84
EP 90
DI 10.1016/j.jenvrad.2016.07.001
PG 7
WC Environmental Sciences
SC Environmental Sciences & Ecology
GA EF7KF
UT WOS:000390507800010
PM 27442258
ER
PT J
AU Chernyayskiy, P
Kendall, GM
Wakeford, R
Little, MP
AF Chernyayskiy, P.
Kendall, G. M.
Wakeford, R.
Little, M. P.
TI Spatial prediction of naturally occurring gamma radiation in Great
Britain
SO JOURNAL OF ENVIRONMENTAL RADIOACTIVITY
LA English
DT Article
DE Natural gamma radiation; Kriging; Variogram; Multi-resolution Gaussian
process; Childhood cancer; Ordinary least squares
ID CHILDHOOD LEUKEMIA INCIDENCE; BACKGROUND-RADIATION; IONIZING-RADIATION;
TERRESTRIAL; EXPOSURE; MODELS; RADON
AB Gamma radiation from natural sources is an important component of background radiation, and correlates with childhood leukaemia risk in Great Britain. The geographic variation of indoor gamma radiation dose-rates in Great Britain is explored using various geo-statistical methods. A multi-resolution Gaussian-process model using radial basis functions with 2, 4, or 8 components, is fitted via maximum likelihood, and a non-spatial model is also used, fitted by ordinary least squares. Because of the dataset size (N = 10,199), four other parametric spatial models are fitted by variogram-fitting. A randomly selected 70:30 split is used for fitting:validation. The models are evaluated based on their predictive performance as measured by Mean Absolute Error, Mean Squared Error, as well as Pearson correlation and rank-correlation between predicted and actual dose-rates. Each of the four parametric models (Matern, Gaussian, Bessel, Spherical) fitted the empirical variogram well, and yielded similar predictions at >50 km separation, although with more substantial differences in predicted variograms at <50 km. The multi-resolution Gaussian-process model with 8 components had the best predictive accuracy among the models considered. The Spherical, Bessel, Matern, Gaussian and ordinary least squares models had progressively worse predictive performance, the ordinary least squares model being particularly poor in this respect. Published by Elsevier Ltd.
C1 [Chernyayskiy, P.; Little, M. P.] NCI, Radiat Epidemiol Branch, DHHS, NIH,Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Kendall, G. M.] Univ Oxford, Canc Epidemiol Unit, Richard Doll Bldg,Old Rd Campus, Oxford OX3 7LF, England.
[Wakeford, R.] Univ Manchester, Inst Populat Hlth, Ctr Occupat & Environm Hlth, Ellen Wilkinson Bldg,Oxford Rd, Manchester M13 9PL, Lancs, England.
RP Little, MP (reprint author), NCI, Room 7E546,9609 Med Ctr Dr, Rockville, MD 20892 USA.
EM pavel.chernyayskiy@nih.gov; gerald.kendall@ceu.ox.ac.uk;
richard.wakeford@gmail.com; mark.little@nih.gov
OI Wakeford, Richard/0000-0002-2934-0987; Little, Mark/0000-0003-0980-7567;
Kendall, Gerald/0000-0002-9561-1837
FU Intramural Research Program of the National Institutes of Health, the
National Cancer Institute, Division of Cancer Epidemiology and Genetics;
Children with Cancer (UK) [HTRVVK0]
FX We are very grateful to for the detailed comments of the referee and to
Dr Jill Simpson of the University of York and to the other UKCCS
investigators for making available the indoor gamma-ray dose-rate
measurements made for the United Kingdom Childhood Cancer Study and for
advice on the interpretation of the data. We are also very grateful to
Mr JD Appleton for advice on geological matters generally and in
particular for suggesting geological classification schemes. We are
grateful to Drs Phil Gilvin, Luke Hager and Rick Tanner at Public Health
England (PHE) for advice on the dosimetry of the National Survey and the
UKCCS, and to Dr Simon Bouffler and other colleagues at PHE for allowing
the use of the National Survey data and for advice on its
interpretation. We are grateful to Tim Vincent for help with the census
data. This work was supported by the Intramural Research Program of the
National Institutes of Health, the National Cancer Institute, Division
of Cancer Epidemiology and Genetics. The work of GMK was supported by
Children with Cancer (UK) under grant number HTRVVK0.
NR 30
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PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0265-931X
EI 1879-1700
J9 J ENVIRON RADIOACTIV
JI J. Environ. Radioact.
PD NOV
PY 2016
VL 164
BP 300
EP 311
DI 10.1016/j.jenvrad.2016.07.029
PG 12
WC Environmental Sciences
SC Environmental Sciences & Ecology
GA EF7KF
UT WOS:000390507800035
PM 27544074
ER
PT J
AU Papamichael, D
Renfro, LA
Matthaiou, C
Yothers, G
Saltz, L
Guthrie, KA
Van Cutsem, E
Schmoll, HJ
Labianca, R
Andre, T
O'Connell, M
Alberts, SR
Haller, DG
Kountourakis, P
Sargent, DJ
AF Papamichael, Demetris
Renfro, Lindsay A.
Matthaiou, Christiana
Yothers, Greg
Saltz, Leonard
Guthrie, Katherine A.
Van Cutsem, Eric
Schmoll, Hans-Joachim
Labianca, Roberto
Andre, Thierry
O'Connell, Michael
Alberts, Steven R.
Haller, Daniel G.
Kountourakis, Panteleimon
Sargent, Daniel J.
CA Adjuvant Colon Cancer Endpoints
TI Validity of Adjuvant! Online in older patients with stage III colon
cancer based on 2967 patients from the ACCENT database
SO JOURNAL OF GERIATRIC ONCOLOGY
LA English
DT Article
DE Colorectal; Older; Adjuvant; ACCENT
ID PHASE-III; RANDOMIZED-TRIAL; POOLED ANALYSIS; FLUOROURACIL; LEUCOVORIN;
OXALIPLATIN; SURVIVAL; CHEMOTHERAPY; LEVAMISOLE; IRINOTECAN
AB Background: Adjuvant! Online is a tool used for clinical decision making in patients with early stage colon cancer. As details of the tool's construction are not published, the ability of Adjuvant! Online to accurately predict outcomes for older patients (age 70+) with node positive colon cancer receiving adjuvant chemotherapy is unclear.
Methods: Individual data from older patients with stage III colon cancer who enrolled into multiple trials within the ACCENT database were entered into the Adjuvant! Online program to obtain predicted probabilities of 5-year overall survival (OS) and recurrence-free survival (RFS). Median predictions were compared with known rates. As co-morbidities were not known for ACCENT patients, but required for calculator entry, patients were assumed to have either "minor" or "average for age" co-morbidities.
Results: 2967 older patients from 10 randomized studies were included. When "minor" co-morbidities were assumed, the median predicted 5-year OS rate of 64% nearly matched the actual rate of 65%; when "average for age" co-morbidities were assumed, the median prediction dropped to 58%, outside the CI for the actual rate. On the other hand, assuming "minor" co-morbidities gave a median 5-year RFS prediction of 62%, outside the 95% CI for the actual rate of 58%, while assuming "average for age" co-morbidities yielded a better median prediction of 57%.
Conclusion: Adjuvant! Online is reasonably accurate overall for predicting outcomes in older trial patients with stage III colon cancer, though accuracy may differ between 5-year RFS and 5-year OS predictions when a fixed degree of co-morbidities is assumed. (C) 2016 Elsevier Ltd. All rights reserved.
C1 [Papamichael, Demetris; Matthaiou, Christiana; Kountourakis, Panteleimon] BO Cyprus Oncol Ctr, Nicosia, Cyprus.
[Renfro, Lindsay A.; Alberts, Steven R.; Sargent, Daniel J.] Mayo Clin, Rochester, MN USA.
[Yothers, Greg; O'Connell, Michael] Natl Surg Adjuvant Breast & Bowel Project, Pittsburgh, PA USA.
[Saltz, Leonard] Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA.
[Guthrie, Katherine A.] SWOG Southwest Oncol Grp, Ctr Stat, Seattle, WA USA.
[Van Cutsem, Eric] Univ Hosp Gasthuisberg, Gasthuisberg, Belgium.
[Schmoll, Hans-Joachim] Martin Luther Univ Halle Wittenberg, Berlin, Germany.
[Labianca, Roberto; Andre, Thierry] Hop St Antoine, Paris, France.
[Sargent, Daniel J.] Univ Penn, Abrarnson Canc Ctr, Philadelphia, PA 19104 USA.
RP Papamichael, D (reprint author), Bank Cyprus Oncol Ctr, Dept Med Oncol, 32 Acropoleos Ave, CY-2006 Nicosia, Cyprus.
EM demetris.papamichael@bococ.org.cy
FU National Cancer Institute at the National Institutes of Health [CA
25224]
FX This work was supported by the National Cancer Institute at the National
Institutes of Health [grant number CA 25224].
NR 21
TC 0
Z9 0
U1 1
U2 1
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1879-4068
EI 1879-4076
J9 J GERIATR ONCOL
JI J. Geriatr. Oncol.
PD NOV
PY 2016
VL 7
IS 6
BP 422
EP 429
DI 10.1016/j.jgo.2016.07.002
PG 8
WC Oncology; Geriatrics & Gerontology
SC Oncology; Geriatrics & Gerontology
GA EF9GS
UT WOS:000390639300003
PM 27468630
ER
PT J
AU Xu, C
Hu, S
Chen, XY
AF Xu, Can
Hu, Shuo
Chen, Xiaoyuan
TI Artificial cells: from basic science to applications
SO MATERIALS TODAY
LA English
DT Article
ID MEMBRANE-COATED NANOPARTICLES; RED-BLOOD-CELLS; GIANT VESICLES;
SYNTHETIC BIOLOGY; SEMIPERMEABLE MICROCAPSULES; ESCHERICHIA-COLI;
GENE-EXPRESSION; DRUG-DELIVERY; MINIMAL CELL; SELF-REPRODUCTION
AB Artificial cells have attracted much attention as substitutes for natural cells. There are many different forms of artificial cells with many different definitions. They can be integral biological cell imitators with cell-like structures and exhibit some of the key characteristics of living cells. Alternatively, they can be engineered materials that only mimic some of the properties of cells, such as surface characteristics, shapes, morphology, or a few specific functions. These artificial cells can have applications in many fields from medicine to environment, and may be useful in constructing the theory of the origin of life. However, even the simplest unicellular organisms are extremely complex and synthesis of living artificial cells from inanimate components seems very daunting. Nevertheless, recent progress in the formulation of artificial cells ranging from simple protocells and synthetic cells to cell-mimic particles, suggests that the construction of living life is now not an unrealistic goal. This review aims to provide a comprehensive summary of the latest developments in the construction and application of artificial cells, as well as highlight the current problems, limitations, challenges and opportunities in this field.
C1 [Xu, Can; Hu, Shuo] Cent S Univ, Xiangya Hosp, Dept PET Ctr, Changsha 410008, Hunan, Peoples R China.
[Xu, Can; Chen, Xiaoyuan] Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD USA.
RP Hu, S (reprint author), Cent S Univ, Xiangya Hosp, Dept PET Ctr, Changsha 410008, Hunan, Peoples R China.; Chen, XY (reprint author), Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD USA.
EM hushuo_xy@163.com; shawn.chen@nih.gov
NR 152
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Z9 0
U1 25
U2 25
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1369-7021
EI 1873-4103
J9 MATER TODAY
JI Mater. Today
PD NOV
PY 2016
VL 19
IS 9
BP 516
EP 532
DI 10.1016/j.mattod.2016.02.020
PG 17
WC Materials Science, Multidisciplinary
SC Materials Science
GA EF8XA
UT WOS:000390614100013
PM 28077925
ER
PT J
AU Ouadani, H
Ben-Mustapha, I
Ben-Ali, M
Largueche, B
Jovanic, T
Garcia, S
Arcangioli, B
Elloumi-Zghal, H
Fathallah, D
Hachicha, M
Masmoudi, H
Rougeon, F
Barbouche, MR
AF Ouadani, Hanen
Ben-Mustapha, Imen
Ben-ali, Meriem
Largueche, Beya
Jovanic, Tihana
Garcia, Sylvie
Arcangioli, Benoit
Elloumi-Zghal, Houda
Fathallah, Dahmani
Hachicha, Mongia
Masmoudi, Hatem
Rougeon, Francois
Barbouche, Mohamed-Ridha
TI Activation induced cytidine deaminase mutant (AID-His130Pro) from Hyper
IgM 2 patient retained mutagenic activity on SHM artificial substrate
SO MOLECULAR IMMUNOLOGY
LA English
DT Article
DE Activation induced cytidine deaminase; Class switch recombination;
Somatic hypermutation; AID mutagenic activity; Cofactors; Hyper IgM 2
ID CLASS-SWITCH RECOMBINATION; SOMATIC HYPERMUTATION; SYNDROME TYPE-2; AID;
DNA; GENE; EXPRESSION; MUTATION; REGION; DIVERSIFICATION
AB Activation induced cytidine deaminase (AID) is an essential enzyme for class switch recombination (CSR) and somatic hypermutation (SHM) during secondary immune response. Mutations in the AICDA gene are responsible for Hyper IgM 2 syndrome where both CSR and SHM or only CSR are affected. Indeed, triggering either of the two mechanisms requires the DNA deamination activity of AID. Besides, different domains of AID may be differentially involved in CSR and SHM through their interaction with specific cofactors. Herein, we studied the AID-induced SHM activity of the AID-His130Pro mutant identified in a patient with Hyper IgM 2 syndrome. AID mutagenic activity was monitored by the reversion of nonsense mutations of the EGFP gene assessed by flow cytometry. We found that the His130Pro mutation, which affects CSR, preserves AID mutagenic activity. Indeed, the His130 residue is located in a putative specific CSR region in the APOBEC-like domain, known to involve CSR specific cofactors that probably play a major role in AID physiological activities. (C) 2016 Elsevier Ltd. All rights reserved.
C1 [Ouadani, Hanen; Ben-Mustapha, Imen; Ben-ali, Meriem; Largueche, Beya; Elloumi-Zghal, Houda; Fathallah, Dahmani; Barbouche, Mohamed-Ridha] Inst Pasteur Tunis, Lab Transmiss Control & Immunobiol Infect LR11IPT, 13 Pl Pasteur BP74, Tunis 1002, Tunisia.
[Ouadani, Hanen; Ben-Mustapha, Imen; Ben-ali, Meriem; Barbouche, Mohamed-Ridha] Univ Tunis El Manar, Tunis, Tunisia.
[Jovanic, Tihana; Rougeon, Francois] Inst Pasteur Paris, Biochem & Genet Dev Unit URA CNRS 2581, Paris, France.
[Garcia, Sylvie] Inst Pasteur Paris, Lab Lymphocyte Populat Biol, Paris, France.
[Arcangioli, Benoit] Inst Pasteur Paris, Lab Dynam Genome, Paris, France.
[Hachicha, Mongia] Hedi Chaker Hosp, Dept Pediat, Sfax, Tunisia.
[Masmoudi, Hatem] Habib Bourguiba Hosp, Immunol Lab, Sfax, Tunisia.
[Jovanic, Tihana] Howard Huges Med Inst, Janelia Res Campus, Ashburn, VA USA.
[Elloumi-Zghal, Houda] NIAID, Lab Clin Infect Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Fathallah, Dahmani] Arabian Gulf Univ, Coll Postgrad Studies, Manama, Bahrain.
RP Barbouche, MR (reprint author), Inst Pasteur Tunis, Lab Transmiss Control & Immunobiol Infect LR11IPT, 13 Pl Pasteur BP74, Tunis 1002, Tunisia.
EM ridha.barbouche@pasteur.rns.tn
FU Ministry of Health (Tunisia)
FX This work was supported by the Ministry of Health (Tunisia).
NR 47
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U1 1
U2 1
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0161-5890
J9 MOL IMMUNOL
JI Mol. Immunol.
PD NOV
PY 2016
VL 79
BP 77
EP 82
DI 10.1016/j.molimm.2016.09.025
PG 6
WC Biochemistry & Molecular Biology; Immunology
SC Biochemistry & Molecular Biology; Immunology
GA EG0JL
UT WOS:000390718500009
PM 27716525
ER
PT J
AU Smith-Vikos, T
Liu, ZY
Parsons, C
Gorospe, M
Ferrucci, L
Gill, TM
Slack, FJ
AF Smith-Vikos, Thalyana
Liu, Zuyun
Parsons, Christine
Gorospe, Myriam
Ferrucci, Luigi
Gill, Thomas M.
Slack, Frank J.
TI A serum miRNA profile of human longevity: findings from the Baltimore
Longitudinal Study of Aging (BLSA)
SO AGING-US
LA English
DT Article
DE miRNA; aging; long-lived; short-lived; biomarker; longitudinal study
ID POLY(ADP-RIBOSE) POLYMERASE-ACTIVITY; AGE-RELATED DISEASES; CIRCULATING
MICRORNAS; BIOMARKERS; CANCER; CENTENARIANS; BLOOD; EXPRESSION;
PROGNOSIS; DIAGNOSIS
AB In C. elegans, miRNAs are genetic biomarkers of aging. Similarly, multiple miRNAs are differentially expressed between younger and older persons, suggesting that miRNA-regulated biological mechanisms affecting aging are evolutionarily conserved. Previous human studies have not considered participants' lifespans, a key factor in identifying biomarkers of aging. Using PCR arrays, we measured miRNA levels from serum samples obtained longitudinally at ages 50, 55, and 60 from 16 non-Hispanic males who had documented lifespans from 58 to 92. Numerous miRNAs showed significant changes in expression levels. At age 50, 24 miRNAs were significantly upregulated, and 73 were significantly downregulated in the long-lived subgroup (76-92 years) as compared with the short-lived subgroup (58-75 years). In long-lived participants, the most upregulated was miR-373-5p, while the most downregulated was miR-15b-5p. Longitudinally, significant Pearson correlations were observed between lifespan and expression of nine miRNAs (p value<0.05). Six of these nine miRNAs (miR-211-5p, 374a-5p, 340-3p, 376c-3p, 5095, 1225-3p) were also significantly up- or downregulated when comparing long-lived and short-lived participants. Twenty-four validated targets of these miRNAs encoded aging-associated proteins, including PARP1, IGF1R, and IGF2R. We propose that the expression profiles of the six miRNAs (miR-211-5p, 374a-5p, 340-3p, 376c-3p, 5095, and 1225-3p) may be useful biomarkers of aging.
C1 [Smith-Vikos, Thalyana; Slack, Frank J.] Yale Univ, Dept Mol Cellular & Dev Biol, New Haven, CT 06520 USA.
[Liu, Zuyun; Gill, Thomas M.] Yale Sch Med, Dept Internal Med, New Haven, CT 06510 USA.
[Parsons, Christine] Bowdoin Coll, Brunswick, ME 04011 USA.
[Gorospe, Myriam; Ferrucci, Luigi] NIA, Intramural Res Program, Baltimore, MD 21224 USA.
[Slack, Frank J.] Harvard Med Sch, Dept Pathol, Beth Israel Deaconess Med Ctr, Inst RNA Med, Boston, MA 02215 USA.
[Smith-Vikos, Thalyana] Columbia Univ, Grad Sch Arts & Sci, New York, NY 10027 USA.
RP Slack, FJ (reprint author), Yale Univ, Dept Mol Cellular & Dev Biol, New Haven, CT 06520 USA.; Slack, FJ (reprint author), Harvard Med Sch, Dept Pathol, Beth Israel Deaconess Med Ctr, Inst RNA Med, Boston, MA 02215 USA.
EM fslack@bidmc.harvard.edu
FU NIH [AG033921]; Claude D. Pepper Older Americans Independence Center
[P30AG021342]; Academic Leadership Award from the National Institute on
Aging [K07AG3587]
FX This research was supported by a grant to Dr. Slack from the NIH
(AG033921) and by the Claude D. Pepper Older Americans Independence
Center (P30AG021342). Dr. Gill is the recipient of an Academic
Leadership Award (K07AG3587) from the National Institute on Aging.
NR 43
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U1 0
U2 0
PU IMPACT JOURNALS LLC
PI ALBANY
PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA
SN 1945-4589
J9 AGING-US
JI Aging-US
PD NOV
PY 2016
VL 8
IS 11
BP 2971
EP 2987
DI 10.18632/aging.101106
PG 17
WC Cell Biology
SC Cell Biology
GA EF4PA
UT WOS:000390311900028
PM 27824314
ER
PT J
AU Gong, Y
Shao, Z
Fu, ZJ
Edin, ML
Sun, Y
Liegl, RG
Wang, ZX
Liu, CH
Burnim, SB
Meng, SS
Lih, FB
SanGiovanni, JP
Zeldin, DC
Hellstrom, A
Smith, LEH
AF Gong, Yan
Shao, Zhuo
Fu, Zhongjie
Edin, Matthew L.
Sun, Ye
Liegl, Raffael G.
Wang, Zhongxiao
Liu, Chi-Hsiu
Burnim, Samuel B.
Meng, Steven S.
Lih, Fred B.
SanGiovanni, John Paul
Zeldin, Darryl C.
Hellstrom, Ann
Smith, Lois E. H.
TI Fenofibrate Inhibits Cytochrome P450 Epoxygenase 2C Activity to Suppress
Pathological Ocular Angiogenesis
SO EBIOMEDICINE
LA English
DT Article
DE Fenofibrate; Choroidal neovascularization; Retinopathy; Retinal
neovascularization; Cytochrome P450 epoxygenase 2C; Omega-3 long-chain
polyunsaturated fatty acids
ID POLYUNSATURATED FATTY-ACIDS; ENDOTHELIAL GROWTH-FACTOR; RANDOMIZED
CONTROLLED-TRIAL; OXYGEN-INDUCED RETINOPATHY; DIABETIC-RETINOPATHY;
PPAR-ALPHA; CHOROIDAL NEOVASCULARIZATION; MACULAR DEGENERATION; MOUSE;
METABOLITES
AB Neovascular eye diseases including retinopathy of prematurity, diabetic retinopathy and age-related-macular-degeneration are major causes of blindness. Fenofibrate treatment in type 2 diabetes patients reduces progression of diabetic retinopathy independent of its peroxisome proliferator-activated receptor (PPAR)alpha agonist lipid lowering effect. The mechanism is unknown. Fenofibrate binds to and inhibits cytochrome P450 epoxygenase (CYP) 2C with higher affinity than to PPAR alpha. CYP2C metabolizes omega-3 long-chain polyunsaturated fatty acids (LCPUFAs). While omega-3 LCPUFA products from other metabolizing pathways decrease retinal and choroidal neovascularization, CYP2C products of both omega-3 and omega-6 LCPUFAs promote angiogenesis. We hypothesized that fenofibrate inhibits retinopathy by reducing CYP2C omega-3 LCPUFA (and omega-6 LCPUFA) pro-angiogenic metabolites. Fenofibrate reduced retinal and choroidal neovascularization in PPAR alpha-/-mice and augmented omega-3 LCPUFA protection via CYP2C inhibition. Fenofibrate suppressed retinal and choroidal neovascularization in mice overexpressing human CYP2C8 in endothelial cells and reduced plasma levels of the pro-angiogenic.-3 LCPUFA CYP2C8 product, 19,20-epoxydocosapentaenoic acid. 19,20-epoxydocosapentaenoic acid reversed fenofibrate-induced suppression of angiogenesis ex vivo and suppression of endothelial cell functions in vitro. In summary fenofibrate suppressed retinal and choroidal neovascularization via CYP2C inhibition as well as by acting as an agonist of PPAR alpha. Fenofibrate augmented the overall protective effects of omega-3 LCPUFAs on neovascular eye diseases. (C) 2016 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://reativecommons.org/licenses/by-nc-nd/4.0/).
C1 [Gong, Yan; Shao, Zhuo; Fu, Zhongjie; Sun, Ye; Liegl, Raffael G.; Wang, Zhongxiao; Liu, Chi-Hsiu; Burnim, Samuel B.; Meng, Steven S.; Smith, Lois E. H.] Harvard Med Sch, Boston Childrens Hosp, Dept Ophthalmol, Boston, MA 01248 USA.
[Edin, Matthew L.; Lih, Fred B.; Zeldin, Darryl C.] NIEHS, Div Intramural Res, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.
[SanGiovanni, John Paul] NIAAA, Sect Nutrit Neurosci, Lab Membrane Biophys & Biochem, NIH, Bethesda, MD 20892 USA.
[Hellstrom, Ann] Univ Gothenburg, Sahlgrenska Acad, Dept Ophthalmol, S-40530 Gothenburg, Sweden.
RP Smith, LEH (reprint author), 300 Longwood Ave, Boston, MA 02115 USA.
EM lois.smith@childrens.harvard.edu
FU NEI NIH HHS [R24 EY024864]; NICHD NIH HHS [U54 HD090255]
NR 61
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U1 1
U2 1
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 2352-3964
J9 EBIOMEDICINE
JI EBioMedicine
PD NOV
PY 2016
VL 13
BP 201
EP 211
DI 10.1016/j.ebiom.2016.09.025
PG 11
WC Medicine, General & Internal
SC General & Internal Medicine
GA EG0EU
UT WOS:000390704800035
PM 27720395
ER
PT J
AU Gonzalez, NL
O'Brien, KM
D'Aloisio, AA
Sandler, DP
Weinberg, CR
AF Gonzalez, Nicole L.
O'Brien, Katie M.
D'Aloisio, Aimee A.
Sandler, Dale P.
Weinberg, Clarice R.
TI Douching, Talc Use, and Risk of Ovarian Cancer
SO EPIDEMIOLOGY
LA English
DT Article
ID EXPOSURE; WOMEN; METAANALYSIS; PHTHALATE; HEALTH; STATES; CELL
AB Background: Douching was recently reported to be associated with elevated levels of urinary metabolites of endocrine disrupting phthalates, but there is no literature on douching in relation to ovarian cancer. Numerous case-control studies of genital talc use have reported an increased risk of ovarian cancer, but prospective cohort studies have not uniformly confirmed this association. Behavioral correlation between talc use and douching could produce confounding.
Methods: The Sister Study (2003-2009) enrolled and followed 50,884 women in the US and Puerto Rico who had a sister diagnosed with breast cancer. At baseline, participants were asked about douching and talc use during the previous 12 months. During follow-up (median of 6.6 years), 154 participants reported a diagnosis of ovarian cancer. We computed adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for ovarian cancer risk using the Cox proportional hazards model.
Results: There was little association between baseline perineal talc use and subsequent ovarian cancer (HR: 0.73, CI: 0.44, 1.2). Douching was more common among talc users (odds ratio: 2.1, CI: 2.0, 2.3), and douching at baseline was associated with increased subsequent risk of ovarian cancer (HR: 1.8, CI: 1.2, 2.8).
Conclusions: Douching but not talc use was associated with increased risk of ovarian cancer in the Sister Study.
C1 [Gonzalez, Nicole L.; O'Brien, Katie M.; Weinberg, Clarice R.] NIEHS, Biostat & Computat Biol Branch, POB 12233, Res Triangle Pk, NC 27709 USA.
[D'Aloisio, Aimee A.] Social & Sci Syst Inc, Durham, NC USA.
[Sandler, Dale P.] NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA.
RP Weinberg, CR (reprint author), 111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA.
EM weinber2@niehs.nih.gov
OI O'Brien, Katie/0000-0002-1931-1349; Sandler, Dale/0000-0002-6776-0018
FU National Institutes of Health, National Institute of Environmental
Health Sciences [Z01-ES044005]
FX Supported by the Intramural Research Program of the National Institutes
of Health, National Institute of Environmental Health Sciences (Project
Z01-ES044005 to DPS).
NR 26
TC 0
Z9 0
U1 4
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1044-3983
EI 1531-5487
J9 EPIDEMIOLOGY
JI Epidemiology
PD NOV
PY 2016
VL 27
IS 6
BP 797
EP 802
DI 10.1097/EDE.0000000000000528
PG 6
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA EF3UZ
UT WOS:000390251500007
PM 27327020
ER
PT J
AU Radin, RG
Mikkelsen, EM
Rothman, KJ
Hatch, EE
Sorensen, HT
Riis, AH
Kuohung, W
Wise, LA
AF Radin, Rose G.
Mikkelsen, Ellen M.
Rothman, Kenneth J.
Hatch, Elizabeth E.
Sorensen, Henrik T.
Riis, Anders H.
Kuohung, Wendy
Wise, Lauren A.
TI Cesarean Delivery and Subsequent Fecundability
SO EPIDEMIOLOGY
LA English
DT Article
ID PRIMARY-MODE; LIVE BIRTH; 1ST BIRTH; SECTION; FERTILITY; PREGNANCY;
COHORT; REGISTER; IMPACT; WOMEN
AB Background: Studies have shown that cesarean delivery is associated with fewer subsequent births relative to vaginal delivery, but it is unclear whether confounding by pregnancy intention or indication for surgery explained these results. We evaluated the association between cesarean delivery and subsequent fecundability among 910 primiparous women after singleton live birth.
Methods: In a cohort of Danish women planning pregnancy (2007-2012), obstetrical history was obtained via registry linkage; time-to-pregnancy and covariate data were collected via questionnaire. Fecundability ratios (FRs) and 95% confidence intervals (CIs) were adjusted for potential confounders.
Results: Relative to spontaneous vaginal delivery, emergency cesarean delivery with cephalic presentation showed little association with fecundability (FR = 1.0, 95% CI = 0.83, 1.3), but cesarean delivery with breech presentation (FR = 0.72, 95% CI = 0.53, 0.97) and planned cesarean delivery with cephalic presentation (FR = 0.51, 95% CI = 0.25, 1.0) were associated with reduced fecundability.
Conclusions: The cesarean-fecundability association varied by previous fetal presentation and emergency status.
C1 [Radin, Rose G.; Rothman, Kenneth J.; Hatch, Elizabeth E.; Wise, Lauren A.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, 715 Albany St, Boston, MA 02118 USA.
[Radin, Rose G.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Intramural Populat Hlth Res, Bethesda, MD USA.
[Mikkelsen, Ellen M.; Sorensen, Henrik T.; Riis, Anders H.] Aarhus Univ Hosp, Dept Clin Epidemiol, Aarhus, Denmark.
[Rothman, Kenneth J.] RTI Hlth Solut, Res Triangle Pk, NC USA.
[Kuohung, Wendy] Boston Univ, Sch Med, Dept Obstet & Gynecol, Boston, MA 02118 USA.
RP Radin, RG (reprint author), Boston Univ, Sch Publ Hlth, Dept Epidemiol, 715 Albany St, Boston, MA 02118 USA.
EM radin@bu.edu
FU National Institutes of Health (NIH) [R21-HD050264]; Danish Medical
Research Council [271-07-0338]; NIH [T32-HD052458]; NIH Intramural
Research Program
FX This study was supported by the National Institutes of Health (NIH)
(R21-HD050264) and the Danish Medical Research Council (271-07-0338).
Rose Radin was supported by NIH Training Grant T32-HD052458 and by the
NIH Intramural Research Program. The content of this article is solely
the responsibility of the authors and does not necessarily represent the
official views of the National Institutes of Health.
NR 40
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U1 3
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1044-3983
EI 1531-5487
J9 EPIDEMIOLOGY
JI Epidemiology
PD NOV
PY 2016
VL 27
IS 6
BP 889
EP 893
DI 10.1097/EDE.0000000000000553
PG 5
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA EF3UZ
UT WOS:000390251500019
PM 27571458
ER
PT J
AU Turkbey, B
Choyke, PL
AF Turkbey, Baris
Choyke, Peter L.
TI Prostate cancer imaging: a special focus issue from Future Oncology
SO FUTURE ONCOLOGY
LA English
DT Editorial Material
DE imaging; multi-parametric MRI; prostate cancer
C1 [Turkbey, Baris; Choyke, Peter L.] NCI, NIH, Mol Imaging Program, Bethesda, MD 20892 USA.
RP Turkbey, B (reprint author), NCI, NIH, Mol Imaging Program, Bethesda, MD 20892 USA.
EM ismail.turkbey@nih.gov
NR 9
TC 0
Z9 0
U1 2
U2 2
PU FUTURE MEDICINE LTD
PI LONDON
PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3
1QB, ENGLAND
SN 1479-6694
EI 1744-8301
J9 FUTURE ONCOL
JI Future Oncol.
PD NOV
PY 2016
VL 12
IS 21
BP 2389
EP 2391
DI 10.2217/fon-2016-0396
PG 3
WC Oncology
SC Oncology
GA DZ8PG
UT WOS:000386132500001
PM 27734724
ER
PT J
AU Watson, MJ
George, AK
Maruf, M
Frye, TP
Muthigi, A
Kongnyuy, M
Valayil, SG
Pinto, PA
AF Watson, Matthew J.
George, Arvin K.
Maruf, Mahir
Frye, Thomas P.
Muthigi, Akhil
Kongnyuy, Michael
Valayil, Subin G.
Pinto, Peter A.
TI Risk stratification of prostate cancer: integrating multiparametric MRI,
nomograms and biomarkers
SO FUTURE ONCOLOGY
LA English
DT Review
DE biomarkers; multiparametric MRI; nomograms; prostate; prostate cancer
ID SEMINAL-VESICLE INVASION; PREDICTING EXTRACAPSULAR EXTENSION;
RESONANCE-ULTRASOUND FUSION; IMAGE-GUIDED BIOPSY; PELVIC LYMPH-NODES;
RADICAL PROSTATECTOMY; BIOCHEMICAL RECURRENCE; ACTIVE SURVEILLANCE;
PARTIN TABLES; PATHOLOGICAL STAGE
AB Accurate risk stratification of prostate cancer is achieved with a number of existing tools to ensure the identification of at-risk patients, characterization of disease aggressiveness, prediction of cancer burden and extrapolation of treatment outcomes for appropriate management of the disease. Statistical tables and nomograms using classic clinicopathological variables have long been the standard of care. However, the introduction of multiparametric MRI, along with fusion-guided targeted prostate biopsy and novel biomarkers, are being assimilated into clinical practice. The majority of studies to date present the outcomes of each in isolation. The current review offers a critical and objective assessment regarding the integration of multiparametric MRI and fusion-guided prostate biopsy with novel biomarkers and predictive nomograms in contemporary clinical practice.
C1 [Watson, Matthew J.; George, Arvin K.; Maruf, Mahir; Frye, Thomas P.; Muthigi, Akhil; Kongnyuy, Michael; Valayil, Subin G.; Pinto, Peter A.] NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA.
RP Pinto, PA (reprint author), NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA.
EM pintop@mail.nih.gov
FU Intramural Research Program of the NIH; National Cancer Institute;
Center for Cancer Research; Center for Interventional Oncology; NIH
FX This research was supported by the Intramural Research Program of the
NIH, National Cancer Institute, Center for Cancer Research and the
Center for Interventional Oncology. NIH and Philips Healthcare have a
cooperative research and development agreement. NIH and Philips share
intellectual property in the field. This research was also made possible
through the National Institutes of Health Medical Research Scholars
Program, a public-private partnership supported jointly by the NIH and
generous contributions to the Foundation for the NIH from Pfizer Inc.,
The Doris Duke Charitable Foundation, The Alexandria Real Estate
Equities, Inc. and Mr and Mrs Joel S Marcus and the Howard Hughes
Medical Institute, as well as other private donors. For a complete list,
please visit the Foundation website at:
http://fnih.org/work/education-training-0/medical-research-scholars-prog
ram. 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 materials discussed in
the manuscript apart from those disclosed.
NR 123
TC 2
Z9 2
U1 3
U2 3
PU FUTURE MEDICINE LTD
PI LONDON
PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3
1QB, ENGLAND
SN 1479-6694
EI 1744-8301
J9 FUTURE ONCOL
JI Future Oncol.
PD NOV
PY 2016
VL 12
IS 21
BP 2417
EP 2430
DI 10.2217/fon-2016-0178
PG 14
WC Oncology
SC Oncology
GA DZ8PG
UT WOS:000386132500005
PM 27400645
ER
PT J
AU Mertan, FV
Lindenberg, L
Choyke, PL
Turkbey, B
AF Mertan, Francesca V.
Lindenberg, Liza
Choyke, Peter L.
Turkbey, Baris
TI PET imaging of recurrent and metastatic prostate cancer with novel
tracers
SO FUTURE ONCOLOGY
LA English
DT Review
DE biochemical recurrence; PET; prostate cancer
ID GA-68-LABELED PSMA LIGAND; POSITRON-EMISSION-TOMOGRAPHY; FATTY-ACID
SYNTHASE; C-11-CHOLINE PET/CT; BONE METASTASES; BIOCHEMICAL RECURRENCE;
RADICAL PROSTATECTOMY; MEMBRANE ANTIGEN;
ANTI-1-AMINO-3-F-18-FLUOROCYCLOBUTANE-1-CARBOXYLIC ACID;
F-18-FLUOROCHOLINE PET/CT
AB Early detection of recurrent prostate cancer (PCa) is of paramount importance to deliver prompt and accurate therapy reducing the chance of progression to metastatic disease. However, current imaging modalities such as conventional computed tomography, MRI and PET scanning do not provide sufficient sensitivity, especially at lower prostate-specific antigen values. Moreover, biological characterization of PCa has become increasingly important to provide patient-specific therapy and current imaging poorly characterizes disease aggressiveness. The current uprise of novel PET tracers in recurrent and metastatic PCa shows promising, yet variable sensitivities and specificities in detection, indicating the need for further studies. In this review, we highlight current and new PET tracers that have been developed to improve the detection of recurrent and metastatic PCa.
C1 [Mertan, Francesca V.; Lindenberg, Liza; Choyke, Peter L.; Turkbey, Baris] NCI, Mol Imaging Program, NIH, Bethesda, MD 20892 USA.
RP Turkbey, B (reprint author), NCI, Mol Imaging Program, NIH, Bethesda, MD 20892 USA.
EM turkbeyi@mail.nih.gov
NR 82
TC 1
Z9 1
U1 3
U2 3
PU FUTURE MEDICINE LTD
PI LONDON
PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3
1QB, ENGLAND
SN 1479-6694
EI 1744-8301
J9 FUTURE ONCOL
JI Future Oncol.
PD NOV
PY 2016
VL 12
IS 21
BP 2463
EP 2477
DI 10.2217/fon-2016-0270
PG 15
WC Oncology
SC Oncology
GA DZ8PG
UT WOS:000386132500008
PM 27527923
ER
PT J
AU Switzer, GE
Bruce, J
Kiefer, DM
Kobusingye, H
Drexler, R
Besser, RM
Confer, DL
Horowitz, MM
King, RJ
Shaw, BE
van Walraven, SM
Wiener, L
Packman, W
Varni, JW
Pulsipher, MA
AF Switzer, Galen E.
Bruce, Jessica
Kiefer, Deidre M.
Kobusingye, Hati
Drexler, Rebecca
Besser, RaeAnne M.
Confer, Dennis L.
Horowitz, Mary M.
King, Roberta J.
Shaw, Bronwen E.
van Walraven, Suzanna M.
Wiener, Lori
Packman, Wendy
Varni, James W.
Pulsipher, Michael A.
TI Health-Related Quality of Life among Pediatric Hematopoietic Stem Cell
Donors
SO JOURNAL OF PEDIATRICS
LA English
DT Article
ID BONE-MARROW DONATION; SIBLING DONOR; THE-LITERATURE; EXPERIENCE;
TRANSPLANTATION; PEDSQL(TM)-4.0; RELIABILITY; VALIDITY; HARVEST; SAFETY
AB Objectives To examine health-related quality of life (HRQoL) among sibling pediatric hematopoietic stem cell donors from predonation through 1 year postdonation, to compare donor-reported HRQoL scores with proxy-reports by parents/guardians and those of healthy norms, and to identify predonation factors (including donor age) potentially associated with postdonation HRQoL, to better understand the physical and psychosocial effects of pediatric hematopoietic stem cell donation.
Study design A random sample of 105 pediatric donors from US centers and a parent/guardian were interviewed by telephone predonation and 4 weeks and 1 year postdonation. The interview included sociodemographic, psychosocial, and HRQoL items. A sample of healthy controls matched to donors by age, gender, and race/ethnicity was generated.
Results Key findings included (1) approximately 20% of donors at each time point had very poor HRQoL; (2) child self-reported HRQoL was significantly lower than parent proxy-reported HRQoL at all 3 time points and significantly lower than that of norms at predonation and 4 weeks postdonation; and (3) younger children were at particular risk of poor HRQoL.
Conclusions Additional research to identify the specific sources of poorer HRQoL among at-risk donors (eg, the donation experience vs having a chronically ill sibling) and the reasons that parents may be overestimating HRQoL in their donor children is critical and should lead to interventions and policy changes that ensure positive experiences for these minor donors.
C1 [Switzer, Galen E.] Univ Pittsburgh, Dept Med, Pittsburgh, PA USA.
[Switzer, Galen E.; Bruce, Jessica] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA.
[Switzer, Galen E.] Univ Pittsburgh, Dept Clin & Translat Sci, Pittsburgh, PA USA.
[Switzer, Galen E.] Vet Affairs Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA.
[Kiefer, Deidre M.; Kobusingye, Hati; Drexler, Rebecca; Besser, RaeAnne M.; Confer, Dennis L.; King, Roberta J.] Natl Marrow Donor Program Be Match, Ctr Int Blood & Marrow Transplant Res, Minneapolis, MN USA.
[Horowitz, Mary M.; Shaw, Bronwen E.] Med Coll Wisconsin, Dept Med, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA.
[van Walraven, Suzanna M.] Sanquin Blood Supply, Dept Donor Serv, Amsterdam, Netherlands.
[van Walraven, Suzanna M.] Leiden Univ, Med Ctr, Dept Pediat Stem Cell Transplantat, Willem Alexander Childrens Hosp, Leiden, Netherlands.
[Wiener, Lori] NCI, Ctr Canc Res, Bethesda, MD 20892 USA.
[Packman, Wendy] Palo Alto Univ, Dept Psychol, Palo Alto, CA USA.
[Varni, James W.] Texas A&M Univ, Dept Pediat, College Stn, TX USA.
[Varni, James W.] Texas A&M Univ, Ctr Hlth Syst & Design, Dept Landscape Architecture & Urban Planning, College Stn, TX USA.
[Pulsipher, Michael A.] Childrens Hosp Los Angeles, Div Hematol Oncol & Bone Marrow Transplantat, Los Angeles, CA 90027 USA.
RP Switzer, GE (reprint author), Univ Pittsburgh, 3501 Forbes Ave,Oxford Bldg,Suite 410, Pittsburgh, PA 15213 USA.
EM SwitzerGE@upmc.edu
FU National Heart, Lung, and Blood Institute [R01 HL085707]; Mapi Research
Trust
FX Supported by the National Heart, Lung, and Blood Institute (R01
HL085707). J.V. holds the copyright and the trademark for the Pediatric
Quality of Life Inventory and receives financial compensation from the
Mapi Research Trust, which is a nonprofit research institute that
charges distribution fees to for-profit companies that use the Pediatric
Quality of Life Inventory. The other authors declare no conflicts of
interest.
NR 27
TC 1
Z9 1
U1 4
U2 4
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0022-3476
EI 1097-6833
J9 J PEDIATR-US
JI J. Pediatr.
PD NOV
PY 2016
VL 178
BP 164
EP +
DI 10.1016/j.jpeds.2016.07.009
PG 8
WC Pediatrics
SC Pediatrics
GA EF0ON
UT WOS:000390025400031
PM 27522440
ER
PT J
AU Sindhar, S
Lugo, M
Levin, MD
Danback, JR
Brink, BD
Yu, E
Dietzen, DJ
Clark, AL
Purgert, CA
Waxler, JL
Elder, RW
Pober, BR
Kozel, BA
AF Sindhar, Sampat
Lugo, Michael
Levin, Mark D.
Danback, Joshua R.
Brink, Benjamin D.
Yu, Eric
Dietzen, Dennis J.
Clark, Amy L.
Purgert, Carolyn A.
Waxler, Jessica L.
Elder, Robert W.
Pober, Barbara R.
Kozel, Beth A.
TI Hypercalcemia in Patients with Williams-Beuren Syndrome
SO JOURNAL OF PEDIATRICS
LA English
DT Article
ID INFANTILE HYPERCALCEMIA; VITAMIN-D; CALCIUM; PAMIDRONATE; CHROMOSOME-7;
MANAGEMENT; DIAGNOSIS; DELETIONS; INFUSION; ADULTS
AB Objective To evaluate the timing, trajectory, and implications of hypercalcemia in Williams-Beuren syndrome ( WBS) through a multicenter retrospective study.
Study design Data on plasma calcium levels from 232 subjects with WBS aged 0-67.1 years were compared with that in controls and also with available normative data. Association testing was used to identify relevant comorbidities.
Results On average, individuals with WBS had higher plasma calcium levels than controls, but 86.7% of values were normal. Nonpediatric laboratories overreport hypercalcemia in small children. When pediatric reference intervals were applied, the occurrence of hypercalcemia dropped by 51% in infants and by 38% in toddlers. Across all ages, 6.1% of the subjects had actionable hypercalcemia. In children, actionable hypercalcemia was seen in those aged 5-25 months. In older individuals, actionable hypercalcemia was often secondary to another disease process. Evidence of dehydration, hypercalciuria, and nephrocalcinosis were common in both groups. Future hypercalcemia could not be reliably predicted by screening calcium levels. A subgroup analysis of 91 subjects found no associations between hypercalcemia and cardiovascular disease, gastrointestinal complaints, or renal anomalies. Analyses of electrogradiography data showed an inverse correlation of calcium concentration with corrected QT interval, but no acute life-threatening events were reported.
Conclusions Actionable hypercalcemia in patients with WBS occurs infrequently. Although irritability and lethargy were commonly reported, no mortality or acute life-threatening events were associated with hypercalcemia and the only statistically associated morbidities were dehydration, hypercalciuria, and nephrocalcinosis.
C1 [Sindhar, Sampat; Lugo, Michael; Danback, Joshua R.; Dietzen, Dennis J.; Clark, Amy L.; Purgert, Carolyn A.; Kozel, Beth A.] Washington Univ, Sch Med, Dept Pediat, St Louis, MO 63110 USA.
[Levin, Mark D.; Kozel, Beth A.] NHLBI, NIH, Bldg 10, Bethesda, MD 20892 USA.
[Brink, Benjamin D.; Yu, Eric; Pober, Barbara R.] Quinnipiac Univ, Frank H Netter Sch Med, North Haven, CT USA.
[Waxler, Jessica L.; Pober, Barbara R.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Elder, Robert W.] Yale Univ, Sch Med, Dept Pediat, Sect Cardiol, New Haven, CT 06510 USA.
[Elder, Robert W.] Yale Univ, Sch Med, Dept Internal Med, Sect Cardiol, New Haven, CT 06510 USA.
[Pober, Barbara R.] Harvard Med Sch, Boston, MA USA.
RP Kozel, BA (reprint author), NHLBI, Bldg 10,8N-110, Bethesda, MD 20892 USA.
EM beth.kozel@nih.gov
FU Children's Discovery Institute (Washington University School of
Medicine/St. Louis Children's Hospital) [CH-FR-2011-169]; Division of
Intramural Research of the National Heart, Lung, and Blood Institute;
National Institutes of Health [T32HD043010, T35DK074375]
FX Funded by the Children's Discovery Institute (CH-FR-2011-169 at
Washington University School of Medicine/St. Louis Children's Hospital
[to B.K.]) and the Division of Intramural Research of the National
Heart, Lung, and Blood Institute. A.C. is supported by the National
Institutes of Health (T32HD043010). S.S. was supported by the National
Institutes of Health (T35DK074375). The authors declare no conflicts of
interest.
NR 35
TC 0
Z9 0
U1 0
U2 0
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0022-3476
EI 1097-6833
J9 J PEDIATR-US
JI J. Pediatr.
PD NOV
PY 2016
VL 178
BP 254
EP +
DI 10.1016/j.jpeds.2016.08.027
PG 11
WC Pediatrics
SC Pediatrics
GA EF0ON
UT WOS:000390025400045
PM 27574996
ER
PT J
AU Tamburro, RF
Jenkins, TL
Kochanek, PM
AF Tamburro, Robert F.
Jenkins, Tammara L.
Kochanek, Patrick M.
TI Strategic Planning for Research in Pediatric Critical Care
SO PEDIATRIC CRITICAL CARE MEDICINE
LA English
DT Article
DE mortality; multiple organ dysfunction syndrome; pediatric critical care
medicine; pediatrics; research
ID ORGAN DYSFUNCTION SYNDROME; INTENSIVE-CARE; MORTALITY; CHILDREN
AB Objective: To summarize the scientific priorities and potential future research directions for pediatric critical care research discussed by a panel of experts at the inaugural Strategic Planning Conference of the Pediatric Trauma and Critical Illness Branch of the Eunice Kennedy Shriver National Institute of Child Health and Human Development.
Data Sources: Expert opinion expressed during the Strategic Planning Conference.
Study Selection: Not applicable.
Data Extraction: Chaired by an experienced expert from the field, issues relevant to the conduct of pediatric critical care research were discussed and debated by the invited participants.
Data Synthesis: Common themes and suggested priorities were identified and coalesced.
Conclusions: Of the many pathophysiologic conditions discussed, the multiple organ dysfunction syndrome emerged as a topic in need of more study that is most relevant to the field. Additionally, the experts offered that the interrelationship and impact of critical illness on child development and family functioning are important research priorities. Consequently, long-term outcomes research was encouraged. The expert group also suggested that multidisciplinary conferences are needed to help identify key knowledge gaps to advance and direct research in the field. The Pediatric Critical Care and Trauma Scientist Development National K12 Program and the Collaborative Pediatric Critical Care Research Network were recognized as successful and important programs supported by the branch. The development of core data resources including biorepositories with robust phenotypic data using common data elements was also suggested to foster data sharing among investigators and to enhance disease diagnosis and discovery. Multicenter clinical trials and innovative study designs to address understudied and poorly understood conditions were considered important for field advancement. Finally, the growth of the pediatric critical care research workforce was offered as a priority that could be spawned in many ways including by expanded transdisciplinary and multiprofessional collaboration and diversity representation.
C1 [Tamburro, Robert F.; Jenkins, Tammara L.] Eunice Kennedy Shover Natl Inst Child Hlth & Huma, Pediat Trauma & Crit Illness Branch, NIH, Bethesda, MD 20892 USA.
[Kochanek, Patrick M.] Univ Pittsburgh, Sch Med, Safar Ctr Resuscitat Res, Dept Crit Care Med, Pittsburgh, PA USA.
[Kochanek, Patrick M.] Univ Pittsburgh, Sch Med, Dept Anesthesiol, Safar Ctr Resuscitat Res, Pittsburgh, PA 15261 USA.
[Kochanek, Patrick M.] Univ Pittsburgh, Sch Med, Dept Pediat, Safar Ctr Resuscitat Res, Pittsburgh, PA 15261 USA.
[Kochanek, Patrick M.] Univ Pittsburgh, Sch Med, Dept Bioengn, Safar Ctr Resuscitat Res, Pittsburgh, PA USA.
[Kochanek, Patrick M.] Univ Pittsburgh, Sch Med, Dept Clin & Translat Sci, Safar Ctr Resuscitat Res, Pittsburgh, PA USA.
RP Tamburro, RF (reprint author), Eunice Kennedy Shover Natl Inst Child Hlth & Huma, Pediat Trauma & Crit Illness Branch, NIH, Bethesda, MD 20892 USA.
EM robert.tamburro@nih.gov
FU Springer Publishing; National Institutes of Health; U.S. Army
FX Dr. Tamburro received funding from Springer Publishing and other (the
calfactant used in a multicenter trial of calfactant in acute lung
injury in pediatric hematopoietic stem cell transplant patients was
provided free of charge) and disclosed government work. Dr. Jenkins
disclosed government work. Dr. Kochanek received support for article
research from the National Institutes of Health and U.S. Army.
NR 16
TC 0
Z9 0
U1 1
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1529-7535
EI 1947-3893
J9 PEDIATR CRIT CARE ME
JI Pediatr. Crit. Care Med.
PD NOV
PY 2016
VL 17
IS 11
BP E539
EP E542
DI 10.1097/PCC.0000000000000946
PG 4
WC Critical Care Medicine; Pediatrics
SC General & Internal Medicine; Pediatrics
GA EF2ES
UT WOS:000390138100007
PM 27679964
ER
PT J
AU Guy, GP
Berkowitz, Z
Ekwueme, DU
Rim, SH
Yabroff, KR
AF Guy, Gery P., Jr.
Berkowitz, Zahava
Ekwueme, Donatus U.
Rim, Sun Hee
Yabroff, K. Robin
TI Annual Economic Burden of Productivity Losses Among Adult Survivors of
Childhood Cancers
SO PEDIATRICS
LA English
DT Article
ID HEALTH-INSURANCE COVERAGE; AFFORDABLE CARE ACT; UNITED-STATES; COHORT;
AGREEMENT; OUTCOMES
AB BACKGROUND AND OBJECTIVES: Although adult survivors of childhood cancers have poorer health and greater health limitations than other adults, substantial gaps remain in understanding the economic consequences of surviving childhood cancer. Therefore, we estimated the economic burden of productivity losses among adult survivors of childhood cancers.
METHODS: We examined health status, functional limitations, and productivity loss among adult survivors of childhood cancers (n = 239) diagnosed at = 14 years of age compared with adults without a history of cancer (n = 304 265) by using the 2004-2014 National Health Interview Survey. We estimated economic burden using the productivity loss from health-related unemployment, missed work days, missed household productivity, and multivariable regression models controlling for age, sex, race/ethnicity, education, comorbidities, and survey year.
RESULTS: Childhood cancer survivorship is associated with a substantial economic burden. Adult survivors of childhood cancers are more likely to be in poorer health, need assistance with personal care and routine needs, have work limitations, be unable to work because of health, miss more days of work, and have greater household productivity loss compared with adults without a history of cancer (all P < .05). The annual productivity loss for adult survivors of childhood cancer is $8169 per person compared with $3083 per person for individuals without a history of cancer.
CONCLUSIONS: These findings underscore the importance of efforts to reduce the health and economic burden among adult survivors of childhood cancer. In addition, this study highlights the potential productivity losses that could be avoided during adulthood from the prevention of childhood cancer in the United States.
C1 [Guy, Gery P., Jr.; Berkowitz, Zahava; Ekwueme, Donatus U.; Rim, Sun Hee] Ctr Dis Control & Prevent, Natl Ctr Chron Dis Prevent & Hlth Promot, Div Canc Prevent & Control, Atlanta, GA USA.
[Yabroff, K. Robin] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
RP Guy, GP (reprint author), Ctr Dis Control & Prevent, Div Canc Prevent & Control, 4770 Buford Hwy NE,MS F-76, Chamblee, GA 30341 USA.
EM irm2@cdc.gov
FU US Government
FX All authors are federal government employees, and the preparation of the
manuscript was entirely funded by the US Government.
NR 34
TC 0
Z9 0
U1 1
U2 1
PU AMER ACAD PEDIATRICS
PI ELK GROVE VILLAGE
PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA
SN 0031-4005
EI 1098-4275
J9 PEDIATRICS
JI Pediatrics
PD NOV
PY 2016
VL 138
SU 1
BP S15
EP S21
DI 10.1542/peds.2015-4268D
PG 7
WC Pediatrics
SC Pediatrics
GA EE2LA
UT WOS:000389414300003
PM 27940973
ER
PT J
AU Troisi, R
Hatch, EE
Titus, L
AF Troisi, Rebecca
Hatch, Elizabeth E.
Titus, Linda
TI The Diethylstilbestrol Legacy: A Powerful Case Against Intervention in
Uncomplicated Pregnancy
SO PEDIATRICS
LA English
DT Article
ID EXPOSED IN-UTERO; CANCER RISK; WOMEN; DES; ADENOCARCINOMA; VAGINA
AB Although the basic tenet of medicine is "First, do no harm," history is filled with good intentions that were at best unhelpful and at worst harmful. Because medicine seeks to cure afflictions, there is an overwhelming desire on the part of health providers and patients to administer treatment. In certain settings, treatment can be reasonable despite a risk of adverse consequences: for example, if the disease is cured or its morbidity abated and the treatment consequences are less disabling than the disease itself.
In the absence of overt disease, the question of whether to apply an intervention is far more challenging. The safety of interventions must be weighed against the population's level of risk, the morbidity and/or mortality associated with the disease, and the intervention's efficacy (eg, BRCA1 mutation, mastectomy, reduced breast cancer risk). Interventions must meet an especially high standard of safety and efficacy when administered in low-risk populations or in settings in which the morbidity associated with the disease is minor. In the worst-case scenario, an intervention may be both ineffective for its primary purpose and cause iatrogenic illness.
Interventions in pregnancy are especially problematic because of the complex physiology of the condition and the possibility of causing short- and long-term adverse consequences in both the mother and her offspring. The continuing story of diethylstilbestrol (DES), a synthetic estrogen, shows the importance of caution when evaluating the merits of interventions involving pregnant women. With regard to DES, investigators believed that pregnancy loss was caused in part by a decrease in estrogen and that administering DES to pregnant women would help maintain a healthy pregnancy. Moreover, because endogenous estrogen concentrations increase dramatically during a healthy pregnancy, supplementation with DES was deemed harmless. During its early years of use, DES was administered to women with threatened pregnancy loss or a history of pregnancy loss. Eventually, DES was advertised to the medical community for " routine
C1 [Troisi, Rebecca] NCI, Epidemiol & Biostat Program, Div Epidemiol & Genet, NIH,US Dept HHS, Rockville, MD USA.
[Hatch, Elizabeth E.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.
[Titus, Linda] Geisel Sch Med Dartmouth, Lebanon, NH USA.
[Titus, Linda] Hood Ctr Children & Families, Lebanon, NH USA.
RP Troisi, R (reprint author), NCI, Epidemiol & Biostat Program, Off Director, Div Epidemiol & Genet, 9609-7E578,9609 Med Ctr Dr, Rockville, MD 20850 USA.
EM troisir@mail.nih.gov
FU National Institutes of Health (NIH)
FX Dr. Troisi is an intramural investigator at the National Institutes of
Health. The research upon which this editorial is based was performed
using intramural research funds. Funded by the National Institutes of
Health (NIH).
NR 12
TC 0
Z9 0
U1 1
U2 1
PU AMER ACAD PEDIATRICS
PI ELK GROVE VILLAGE
PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA
SN 0031-4005
EI 1098-4275
J9 PEDIATRICS
JI Pediatrics
PD NOV
PY 2016
VL 138
SU 1
BP S42
EP S44
DI 10.1542/peds.2015-4268G
PG 3
WC Pediatrics
SC Pediatrics
GA EE2LA
UT WOS:000389414300006
PM 27940976
ER
PT J
AU Talbot, JN
Geffert, LM
Jorvig, JE
Goldstein, RI
Nielsen, CL
Wolters, NE
Amos, ME
Munro, CA
Dallman, E
Mereu, M
Tanda, G
Katz, JL
Indarte, M
Madura, JD
Choi, H
Leak, RK
Surratt, CK
AF Talbot, Jeffery N.
Geffert, Laura M.
Jorvig, Jessica E.
Goldstein, Ruben I.
Nielsen, Cienna L.
Wolters, Nicholas E.
Amos, Mary Ellen
Munro, Caitlin A.
Dallman, Elizabeth
Mereu, Maddalena
Tanda, Gianluigi
Katz, Jonathan L.
Indarte, Martin
Madura, Jeffry D.
Choi, Hailey
Leak, Rehana K.
Surratt, Christopher K.
TI Rapid and sustained antidepressant properties of an NMDA
antagonist/monoamine reuptake inhibitor identified via transporter-based
virtual screening
SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR
LA English
DT Article
DE Virtual screen; Monoamine transporter; Ro-25-6981; Ketamine; Serotonin
selective reuptake inhibitor; Antidepressant
ID FORCED SWIM TEST; RESISTANT MAJOR DEPRESSION; D-ASPARTATE ANTAGONIST;
BINDING-SITE; NEUROTRANSMITTER TRANSPORTERS; SEROTONIN TRANSPORTER;
SUBSTRATE-BINDING; NR2B SUBUNIT; KETAMINE; DOPAMINE
AB Rational design of lead compounds targeting monoamine transporters (MATS) is critical to developing novel therapeutics to treat psychiatric disorders including depression and substance abuse. A 3-D dopamine transporter (DAT) computer model was used to virtually screen a commercially available small molecule library for high DAT affinity drug-like compounds. One hit, coded "MI-4", inhibited human dopamine, norepinephrine, and serotonin transporters invitro. In vivo administration in mice induced robust, dose-dependent antidepressant-like behaviors in learned helplessness models (tail suspension and forced swim tests). Moreover, chronic administration (21 day, 10 mg/kg, bid) reduced drinking latencies comparable to fluoxetine (10 mg/kg, bid) in the novelty-induced hypophagia test, which requires chronic treatment to produce antidepressant-like effects. MI-4 (10 mg/kg, bid) produced rapid (three-day) antidepressant-like effects in the social avoidance test following 10 days of social defeat stress. Unlike ketamine, chronic administration of MI-4 increased social interaction scores while improving resiliency to the mood-altering effects of stress to over 70%. Importantly, MI-4 exhibited minimal abuse liability in behavioral and neurological models (conditioned place preference and dopamine in vivo microdialysis). MI-4 was found to be Ro-25-6981, an ifenprodil analog and reputed NMDA antagonist. The data suggest that Ro-25-6981, previously known for rapid-acting glutamatergic antidepressant actions, may also functionally inhibit monoamine reuptake and produces sustained antidepressant effects in vivo. This demonstrates, as proof of principle, the viability of combining these mechanisms to produce rapid and sustained antidepressant-like effects. Overall, these findings suggest MAT computational model-based virtual screening is a viable method for identifying antidepressant lead compounds of unique scaffold. (C) 2016 Elsevier Inc. All rights reserved.
C1 [Talbot, Jeffery N.; Jorvig, Jessica E.; Goldstein, Ruben I.] Roseman Univ Hlth Sci, Coll Pharm, Res Ctr Subst Abuse & Depress, 11 Sunset Way, Henderson, NV 89014 USA.
[Geffert, Laura M.; Choi, Hailey; Leak, Rehana K.; Surratt, Christopher K.] Duquesne Univ, Mylan Sch Pharm, Div Pharmaceut Sci, 600 Forbes Ave, Pittsburgh, PA 15282 USA.
[Nielsen, Cienna L.] Touro Univ Nevada, Dept Basic Sci, 874 Amer Pacific Dr, Henderson, NV 89014 USA.
[Wolters, Nicholas E.; Amos, Mary Ellen; Munro, Caitlin A.; Dallman, Elizabeth] Ohio Northern Univ, Raabe Coll Pharm, 525 S Main St, Ada, OH 45810 USA.
[Mereu, Maddalena; Tanda, Gianluigi; Katz, Jonathan L.] NIDA, Psychobiol Sect, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
[Indarte, Martin] Phusis Therapeut Inc, 3210 Mertyfield Row, San Diego, CA 92121 USA.
[Madura, Jeffry D.] Duquesne Univ, Ctr Computat Sci, Dept Chem, 600 Forbes Ave, Pittsburgh, PA 15282 USA.
[Madura, Jeffry D.] Duquesne Univ, Ctr Computat Sci, Dept Biochem, 600 Forbes Ave, Pittsburgh, PA 15282 USA.
RP Talbot, JN (reprint author), Roseman Univ Hlth Sci, Coll Pharm, Res Ctr Subst Abuse & Depress, 11 Sunset Way, Henderson, NV 89014 USA.; Surratt, CK (reprint author), Duquesne Univ, 437 Mellon Hall,600 Forbes Ave, Pittsburgh, PA 15219 USA.
EM jtalbot@roseman.edu; surratt@duq.edu
RI Tanda, Gianluigi/B-3318-2009;
OI Tanda, Gianluigi/0000-0001-9526-9878; Katz, Jonathan/0000-0002-1068-1159
FU NIDA [R01DA026530, R01DA027806]; U.S. Department of Education
[P116Z050331, P116Z080180]; Bower Bennett Bennett Foundation; Intramural
Research Program of the National Institute on Drug Abuse
FX The authors declare no conflicts of interest regarding the work
described herein. This work was supported by NIDA grants R01DA026530 and
R01DA027806, U.S. Department of Education grants P116Z050331 and
P116Z080180, the Bower Bennett Bennett Foundation, and the Intramural
Research Program of the National Institute on Drug Abuse.
NR 62
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U1 2
U2 2
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0091-3057
J9 PHARMACOL BIOCHEM BE
JI Pharmacol. Biochem. Behav.
PD NOV-DEC
PY 2016
VL 150
BP 22
EP 30
DI 10.1016/j.pbb.2016.08.007
PG 9
WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy
SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy
GA EF1KU
UT WOS:000390084500004
PM 27569602
ER
PT J
AU Bouchelouche, K
Turkbey, B
Choyke, PL
AF Bouchelouche, Kirsten
Turkbey, Baris
Choyke, Peter L.
TI PSMA PET and Radionuclide Therapy in Prostate Cancer
SO SEMINARS IN NUCLEAR MEDICINE
LA English
DT Review
ID POSITRON-EMISSION-TOMOGRAPHY; MONOCLONAL-ANTIBODY J591; LYMPH-NODE
DISSECTION; PSA DOUBLING TIME; MEMBRANE ANTIGEN-EXPRESSION;
OF-THE-LITERATURE; PHASE-I TRIAL; RADICAL PROSTATECTOMY; HIGH-RISK;
BIOCHEMICAL RECURRENCE
AB Prostate cancer (PCa) is the most common malignancy in men and a major cause of cancer death. Accurate imaging plays an important role in diagnosis, staging, restaging, detection of biochemical recurrence, and for therapy of patients with PCa. Because no effective treatment is available for advanced PCa, there is an urgent need to develop new and more effective therapeutic strategies. To optimize treatment outcome, especially in high-risk patients with PCa, therapy for PCa is moving rapidly toward personalization. Medical imaging, including positron emission tomography (PET)/computed tomography (CD, plays an important role in personalized medicine in oncology. In the recent years, much focus has been on prostate specific membrane antigen (PSMA) as a promising target for imaging and therapy with radionuclides, as it is upregulated in most PCa. In the prostate, one potential role for PSMA PET imaging is to help guide focal therapy. Several studies have shown great potential of PSMA PET/CT for initial staging, lymph node staging, and detection of recurrence of PCa, even at very low prostate-specific antigen values after primary therapy. Furthermore, studies have shown that PSMA PET/CT has a higher detection rate than choline PET/CT. Radiolabeled PSMA ligands for therapy show promise in several studies with metastatic PCa and is an area of active investigation. The "image and treat" strategy, with radiolabeled PSMA ligands, has the potential to improve the treatment outcome of patients with PCa and is paving the way for precision medicine in PCa. The aim of this review is to give an overview of recent advancement in PSMA PET and radionuclide therapy for PCa. Published by Elsevier Inc.
C1 [Bouchelouche, Kirsten] Aarhus Univ Hosp, Dept Nucl Med, Palle Juul Jensens Blvd 99, DK-8200 Aarhus, Denmark.
[Bouchelouche, Kirsten] Aarhus Univ Hosp, PET Ctr, Palle Juul Jensens Blvd 99, DK-8200 Aarhus, Denmark.
[Turkbey, Baris; Choyke, Peter L.] NCI, Mol Imaging Program, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Bouchelouche, K (reprint author), Aarhus Univ Hosp, Dept Nucl Med, Palle Juul Jensens Blvd 99, DK-8200 Aarhus, Denmark.; Bouchelouche, K (reprint author), Aarhus Univ Hosp, PET Ctr, Palle Juul Jensens Blvd 99, DK-8200 Aarhus, Denmark.
EM kirsbouc@rm.dk
FU Intramural Program of the National Cancer Institute
FX Peter Choyke and Baris Turkbey received support from the Intramural
Program of the National Cancer Institute.
NR 111
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PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0001-2998
EI 1558-4623
J9 SEMIN NUCL MED
JI Semin. Nucl. Med.
PD NOV
PY 2016
VL 46
IS 6
BP 522
EP 535
DI 10.1053/j.semnuclmed.2016.07.006
PG 14
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA EF1IX
UT WOS:000390079600008
PM 27825432
ER
PT J
AU Lindenberg, L
Ahlman, M
Turkbey, B
Mena, E
Choyke, P
AF Lindenberg, Liza
Ahlman, Mark
Turkbey, Baris
Mena, Esther
Choyke, Peter
TI Advancement of MR and PET/MR in Prostate Cancer
SO SEMINARS IN NUCLEAR MEDICINE
LA English
DT Review
ID SEMINAL-VESICLE INVASION; PLANAR BONE-SCINTIGRAPHY; INTEGRATED
WHOLE-BODY; FUSION-GUIDED BIOPSY; EXTRACAPSULAR EXTENSION;
INITIAL-EXPERIENCE; CHOLINE-PET/CT; METASTASES; METAANALYSIS; DIAGNOSIS
AB Multiparametric magnetic resonance (mpMRI) imaging has assumed a larger role in the diagnosis and management of prostate cancer. The current method of detecting prostate cancer relies on blind systematic biopsy, guided only by transrectal ultrasound that generally directs the needle biopsy to sextants of the prostate rather than specific lesions. MpMRI is playing an increasing role in the detection of primary cancer as it can visualize cancers and direct biopsies. However, even mpMRI is inherently nonspecific and numerous biopsies performed under MR guidance prove to be negative. Positron emission tomography (PET) has the potential to improve the sensitivity and specificity for prostate cancer in combination with mpMRI. Prostate-specific membrane antigen is a widely expressed tumor antigen in prostate cancer for which multiple PET ligands, labeled with Ga-68 and F-18, are being developed. However, the low spatial resolution of PET mandates that it be combined with a higher resolution imaging modality, which typically has been computed tomography (CD. However, MRI is not only better at localizing lesions in the prostate and prostatic bed, but it is also more sensitive than CT for early bone marrow changes in bone metastases caused by prostate cancer. Prostate-specific membrane antigen based PET agents show promise in the early detection of recurrent and metastatic disease. Recent developments in hybrid imaging now allow PET/MRI to be performed simultaneously on a single scanner allowing one-to-one correspondence between the PET activity and MRI findings. This offers the opportunity for both high sensitivity and specificity with excellent anatomic location and could allow for more targeted biopsies and treatments. Here, we review the current status of PET/MRI for prostate cancer. (C) 2016 Published by Elsevier Inc.
C1 [Lindenberg, Liza; Turkbey, Baris; Choyke, Peter] NCI, Mol Imaging Program, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Ahlman, Mark] NIH, Ctr Clin, Dept Radiol & Imaging Sci, Bethesda, MD 20892 USA.
[Mena, Esther] Johns Hopkins Med Inst, Russell H Morgan Dept Radiol & Radiol Sci, 600 N Wolfe St, Baltimore, MD 21205 USA.
RP Choyke, P (reprint author), NCI, Mol Imaging Program, NIH, Bldg 10,Rm B3B69F,10 Ctr Dr, Bethesda, MD 20892 USA.
EM pchoyke@nih.gov
NR 49
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U2 3
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0001-2998
EI 1558-4623
J9 SEMIN NUCL MED
JI Semin. Nucl. Med.
PD NOV
PY 2016
VL 46
IS 6
BP 536
EP 543
DI 10.10536/j.semnuclmed.2016.07.001
PG 8
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA EF1IX
UT WOS:000390079600009
PM 27825433
ER
PT J
AU Wright, TE
Terplan, M
Ondersma, SJ
Boyce, C
Yonkers, K
Chang, G
Creanga, AA
AF Wright, Tricia E.
Terplan, Mishka
Ondersma, Steven J.
Boyce, Cheryl
Yonkers, Kimberly
Chang, Grace
Creanga, Andreea A.
TI The role of screening, brief intervention, and referral to treatment in
the perinatal period
SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
LA English
DT Article
DE alcohol; brief intervention; opioid use; pregnancy; referral to
treatment; screening; substance use disorders; tobacco
ID ILLICIT DRUG-USE; SUBSTANCE-USE; ALCOHOL-USE; PREGNANT-WOMEN;
RANDOMIZED-TRIAL; MECONIUM ANALYSIS; POSTPARTUM WOMEN; CLINICAL CARE;
UNITED-STATES; ABUSE
AB Substance use during pregnancy is at least as common as many of the medical conditions screened for and managed during pregnancy. While harmful and costly, it is often ignored or managed poorly. Screening, brief intervention, and referral to treatment is an evidence-based approach to manage substance use. In September 2012, the US Centers for Disease Control and Prevention convened an Expert Meeting on Perinatal Illicit Drug Abuse to help address key issues around drug use in pregnancy in the United States. This article reflects the formal conclusions of the expert panel that discussed the use of screening, brief intervention, and referral to treatment during pregnancy. Screening for substance use during pregnancy should be universal. It allows stratification of women into zones of risk given their pattern of use. Low-risk women should receive brief advice, those classified as moderate risk should receive a brief intervention, whereas those who are high risk need referral to specialty care. A brief intervention is a patient-centered form of counseling using the principles of motivational interviewing. Screening, brief intervention, and referral to treatment has the potential to reduce the burden of substance use in pregnancy and should be integrated into prenatal care.
C1 [Wright, Tricia E.] Univ Hawaii, John A Burns Sch Med, Dept Obstet Gynecol & Womens Hlth, Honolulu, HI 96822 USA.
[Wright, Tricia E.] Univ Hawaii, John A Burns Sch Med, Dept Psychiat, Honolulu, HI 96822 USA.
[Terplan, Mishka] Behav Hlth Syst, Baltimore, MD USA.
[Ondersma, Steven J.] Wayne State Univ, Merrill Palmer Skillman Inst, Dept Psychiat & Behav Neurosci, Detroit, MI USA.
[Ondersma, Steven J.] Wayne State Univ, Merrill Palmer Skillman Inst, Dept Obstet & Gynecol, Detroit, MI USA.
[Boyce, Cheryl] NIDA, Div Clin Neurosci & Behav Res, NIH, Bethesda, MD 20892 USA.
[Yonkers, Kimberly] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA.
[Yonkers, Kimberly] Yale Univ, Sch Med, Dept Obstet & Gynecol, New Haven, CT 06510 USA.
[Yonkers, Kimberly] Yale Univ, Sch Med, Sch Epidemiol & Publ Hlth, New Haven, CT 06510 USA.
[Chang, Grace] Harvard Med Sch, Dept Psychiat, Boston, MA USA.
[Chang, Grace] Boston Healthcare Syst, Dept Vet Affairs, Dept Psychiat, Brockton, MA USA.
[Creanga, Andreea A.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Int Hlth, Baltimore, MD USA.
[Creanga, Andreea A.] Johns Hopkins Bloomberg Sch Publ Hlth, Int Ctr Maternal & Newborn Hlth, Baltimore, MD USA.
[Creanga, Andreea A.] Ctr Dis Control & Prevent, Div Reprod Hlth, Natl Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA USA.
RP Wright, TE (reprint author), Univ Hawaii, John A Burns Sch Med, Dept Obstet Gynecol & Womens Hlth, Honolulu, HI 96822 USA.; Wright, TE (reprint author), Univ Hawaii, John A Burns Sch Med, Dept Psychiat, Honolulu, HI 96822 USA.
EM tewright@hawaii.edu
NR 65
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U1 4
U2 4
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9378
EI 1097-6868
J9 AM J OBSTET GYNECOL
JI Am. J. Obstet. Gynecol.
PD NOV
PY 2016
VL 215
IS 5
BP 539
EP 547
DI 10.1016/j.ajog.2016.06.038
PG 9
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA EE3RK
UT WOS:000389513700002
PM 27373599
ER
PT J
AU Bernard, MA
AF Bernard, M. A.
TI THE STATE OF NIA BUDGET AND PLANNING
SO GERONTOLOGIST
LA English
DT Meeting Abstract
C1 [Bernard, M. A.] NIA, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0016-9013
EI 1758-5341
J9 GERONTOLOGIST
JI Gerontologist
PD NOV
PY 2016
VL 56
SU 3
BP 471
EP 471
PG 1
WC Gerontology
SC Geriatrics & Gerontology
GA ED1DT
UT WOS:000388585002215
ER
PT J
AU Bernard, MA
AF Bernard, M. A.
TI A CONVERSATION WITH NIA SENIOR LEADERSHIP
SO GERONTOLOGIST
LA English
DT Meeting Abstract
C1 [Bernard, M. A.] NIA, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0016-9013
EI 1758-5341
J9 GERONTOLOGIST
JI Gerontologist
PD NOV
PY 2016
VL 56
SU 3
BP 471
EP 471
PG 1
WC Gerontology
SC Geriatrics & Gerontology
GA ED1DT
UT WOS:000388585002216
ER
PT J
AU Ma, J
Jacques, PF
Hwang, SJ
Troy, LM
McKeown, NM
Chu, AY
Fox, CS
AF Ma, Jiantao
Jacques, Paul F.
Hwang, Shih-Jen
Troy, Lisa M.
McKeown, Nicola M.
Chu, Audrey Y.
Fox, Caroline S.
TI Dietary Guideline Adherence Index and Kidney Measures in the Framingham
Heart Study
SO AMERICAN JOURNAL OF KIDNEY DISEASES
LA English
DT Article
DE Dietary Guidelines for Americans Adherence Index (DGAI); meat and
legumes; dairy products; estimated glomerular filtration rate (eGFR);
incident low eGFR; rapid eGFR decline; renal function; kidney disease
progression; modifiable risk factor; diet; Framingham Heart Study
Offspring Cohort; albuminuria; urinary albumin-creatinine ratio (UACR)
ID FOOD-FREQUENCY QUESTIONNAIRE; CARDIOVASCULAR-DISEASE; RENAL-FUNCTION;
FUNCTION DECLINE; SWEETENED SODA; PROTEIN-INTAKE; RISK-FACTOR;
ASSOCIATIONS; REPRODUCIBILITY; ALBUMINURIA
AB Background: No observational studies have directly considered dietary guidelines when examining the prospective association between dietary intake and kidney measures.
Study Design: Prospective cohort study.
Setting & Participants: We examined participants who attended examinations 7 (1998-2001) and 8 (2005-2008) in the Framingham Offspring Cohort.
Predictors: Individual components of Dietary Guidelines for Americans Adherence Index (DGAI) that reflect adherence to key dietary recommendations based on the 2005 guideline.
Outcomes & Measures: The primary outcome was incident low estimated glomerular filtration rate (eGFR) at follow-up after exclusion of prevalent low eGFR at baseline. Low eGFR was defined as serum creatinine-based eGFR <60 mL/min/1.73 m(2).
Results: Among 1,822 participants (mean age, 59.4 years; 54.6% women), 181 incident cases of low eGFR were identified. After adjustment for potential confounders, compared to optimal adherence to meat and legume recommendations, low adherence was associated with higher odds of incident low eGFR (P for trend = 0.01); ORs in the lowest and intermediate adherence categories were 2.98 (95% CI, 1.13-7.92) and 1.65 (95% CI, 1.02-2.66), respectively. Low adherence to dairy product recommendations was also associated with higher odds of incident low eGFR compared to optimal adherence (P for trend = 0.03); ORs in the lowest and intermediate adherence categories were 1.98 (95% CI, 1.03-3.82) and 1.59 (95% CI, 0.81-3.11), respectively. In addition, low adherence to meat and legume recommendations was associated with rapid eGFR decline (P for trend = 0.01), and low adherence to dairy product recommendations was associated with rapid eGFR decline (P for trend = 0.01) and incident albuminuria (P for trend = 0.03).
Limitations: The DGAI was developed based on the 2005 Dietary Guidelines for Americans.
Conclusions: Better adherence to dietary recommendations for both meat and legumes and dairy products was associated with lower risk for developing adverse kidney measures. Published by Elsevier Inc. on behalf of the National Kidney Foundation, Inc.
C1 [Ma, Jiantao; Hwang, Shih-Jen; Chu, Audrey Y.; Fox, Caroline S.] NHLBI, Framingham Heart Study & Populat Sci Branch, 73 Mt Wayte Ave,Ste 2, Framingham, MA 01702 USA.
[Jacques, Paul F.; McKeown, Nicola M.] Tufts Univ, Jean Mayer USDA Human Nutr Res Ctr Aging, Nutr Epidemiol Program, Boston, MA 02111 USA.
[Troy, Lisa M.] Univ Massachusetts, Dept Nutr, Amherst, MA 01003 USA.
RP Fox, CS (reprint author), NHLBI, Framingham Heart Study & Populat Sci Branch, 73 Mt Wayte Ave,Ste 2, Framingham, MA 01702 USA.
EM foxca@nhlbi.nih.gov
FU NHLBI Framingham Heart Study [N01-HC-25195]
FX This work was conducted in part using resources and data from the
Framingham Heart Study of the National Heart, Lung and Blood Institute
(NHLBI) of the National Institutes of Health (NIH) and Boston University
School of Medicine. This work was supported by the NHLBI Framingham
Heart Study (N01-HC-25195). The funders of this study had no role in
study design; collection, analysis, and interpretation of data; writing
the report; and the decision to submit the report for publication. The
views expressed in this manuscript are those of the authors and do not
necessarily represent the views of the NHLBI, the NIH, or the US
Department of Health and Human Services.
NR 30
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PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0272-6386
EI 1523-6838
J9 AM J KIDNEY DIS
JI Am. J. Kidney Dis.
PD NOV
PY 2016
VL 68
IS 5
BP 703
EP 715
DI 10.1053/j.ajkd.2016.04.015
PG 13
WC Urology & Nephrology
SC Urology & Nephrology
GA EE3QT
UT WOS:000389511300010
PM 27261331
ER
PT J
AU Melamed, N
Pittini, A
Hiersch, L
Yogev, Y
Korzeniewski, SJ
Romero, R
Barrett, J
AF Melamed, Nir
Pittini, Alex
Hiersch, Liran
Yogev, Yariv
Korzeniewski, Steven J.
Romero, Roberto
Barrett, Jon
TI Do serial measurements of cervical length improve the prediction of
preterm birth in asymptomatic women with twin gestations?
SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
LA English
DT Article
DE biomarker; cervical ripening; cervical shortening; cervix; labor;
longitudinal study; prediction; pregnancy; prematurity; preterm labor;
screening; ultrasound
ID RESPIRATORY-DISTRESS-SYNDROME; PARTICIPANT DATA METAANALYSIS;
TRANSVAGINAL SONOGRAPHIC MEASUREMENT; ANTEPARTUM CORTICOSTEROID
TREATMENT; VAGINAL MICRONIZED PROGESTERONE; RANDOMIZED CONTROLLED-TRIAL;
MULTIPLE PREGNANCY PROTWIN; PLURALITY-DEPENDENT RISK; FETAL FIBRONECTIN;
PROSPECTIVE MULTICENTER
AB BACKGROUND: Cervical length at midtrimester is a powerful predictor of preterm birth in twin gestations. However, given the fact that, in some cases, cervical shortening may become evident only later during the second trimester, it seems reasonable that serial monitoring of cervical length may improve the detection of preterm birth in women with twins. However, data in support of such a practice are limited and conflicting. The contradictory results may be related to the fact that in most of these studies, the analysis of the predictive value of serial measurements of cervical length was limited to data derived from only two sequential measurements of cervical length, while data on the predictive value of multiple (>2) measurements are scarce.
OBJECTIVE: We sought to determine whether serial measurements of cervical length can improve the prediction of preterm birth in asymptomatic women with twin gestations compared with a single measurement of cervical length at midgestation.
STUDY DESIGN: This was a retrospective cohort study of women with twin pregnancies followed up in a tertiary medical center from 2012 through 2014. All participants underwent routine measurement of cervical length at midgestation and every 2-3 weeks thereafter until 2832 weeks. For each patient, cervical length was determined at the following time periods: 18+0 to 21+6 weeks (period 1, routine exam), 22+0 to 24+6 weeks (period 2), 25+0 to 27+6 weeks (period 3), and 28+0 to 32+0 weeks (period 4). Measurements of cervical length at periods 2-4 were analyzed in the form of either absolute length (in millimeters) or percent shortening relative to cervical length at period 1. The performance of a stepwise algorithm that incorporated serial measurements of cervical length for the prediction of preterm birth was compared to that achieved with a single measurement of cervical length at period 1.
RESULTS: Overall, 441 women with twin pregnancies who were eligible for the study underwent a total of 2374 cervical length measurements. The association of a short cervix (<10th percentile) with preterm birth at <32 weeks persisted in each of the 4 periods of gestation [ odds ratio (95% confidence interval): 7.2 (3.1-16.5), 15.3 (6.4-36.7), 10.3 (4.4-24.3), and 23.1(8.3-64.1), respectively]. Compared with a single measurement of cervical length at midgestation (period 1), a stepwise algorithm integrating serial cervical length measurements from all 4 successive gestational age periods resulted in a significant increase in the area under the receiver operating characteristic curve (0.917 vs 0.613, P < .001). Similarly, when a target false-positive rate of 5% was used, the same stepwise algorithm was associated with a higher detection rate (69% vs 28%, P< .001), higher positive likelihood ratio (14.54 vs 5.12), and lower negative likelihood ratio (0.32 vs 0.76) for preterm birth at < 32 weeks compared with a single measurement of cervical length at period 1.
CONCLUSION: Integration of serial measurements of cervical length using a stepwise algorithm in asymptomatic women with twin gestations can improve the detection of women at risk of preterm birth. Prospective studies are needed to validate these findings, and to investigate whether improved risk assessment performance is sufficient to offset the additional costs associated with serial cervical length measurements.
C1 [Melamed, Nir; Pittini, Alex; Barrett, Jon] Univ Toronto, Sunnybrook Hlth Sci Ctr, Dept Obstet & Gynecol, Div Maternal Fetal Med, Toronto, ON, Canada.
[Hiersch, Liran; Yogev, Yariv] Tel Aviv Sourasky Med Ctr, Lis Hosp Women, Dept Obstet & Gynecol, Tel Aviv, Israel.
[Korzeniewski, Steven J.; Romero, Roberto] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, Program Perinatal Res & Obstet, Div Intramural Res,NIH, Bethesda, MD USA.
[Korzeniewski, Steven J.; Romero, Roberto] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, Program Perinatal Res & Obstet, Div Intramural Res,NIH, Detroit, MI USA.
[Korzeniewski, Steven J.] Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA.
[Romero, Roberto] Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI USA.
[Korzeniewski, Steven J.; Romero, Roberto] Michigan State Univ, Dept Epidemiol & Biostat, E Lansing, MI 48824 USA.
[Romero, Roberto] Univ Michigan, Dept Obstet & Gynecol, Ann Arbor, MI 48109 USA.
RP Melamed, N (reprint author), Univ Toronto, Sunnybrook Hlth Sci Ctr, Dept Obstet & Gynecol, Div Maternal Fetal Med, Toronto, ON, Canada.
EM nir.melamed@sunnybrook.ca
FU Perinatology Research Branch, Division of Intramural Research, Eunice
Kennedy Shriver National Institute of Child Health and Human Development
(NICHD), National Institutes of Health (NIH); Department of Health and
Human Services; NICHD/NIH [HSN27520130000]
FX This research was supported, in part, by the Perinatology Research
Branch, Division of Intramural Research, Eunice Kennedy Shriver National
Institute of Child Health and Human Development (NICHD), National
Institutes of Health (NIH), Department of Health and Human Services and,
in part, with federal funds from NICHD/NIH under contract no.
HSN27520130000.
NR 134
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U1 2
U2 2
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9378
EI 1097-6868
J9 AM J OBSTET GYNECOL
JI Am. J. Obstet. Gynecol.
PD NOV
PY 2016
VL 215
IS 5
AR 616.e1-14
DI 10.1016/j.ajog.2016.06.034
PG 14
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA EE3RK
UT WOS:000389513700024
PM 27365003
ER
PT J
AU Scheraga, RG
Thompson, C
Tulapurkar, ME
Nagarsekar, AC
Cowan, M
Potla, R
Sun, JF
Cai, RM
Logun, C
Shelhamer, J
Todd, NW
Singh, IS
Luzina, IG
Atamas, SP
Hasday, JD
AF Scheraga, Rachel G.
Thompson, Christopher
Tulapurkar, Mohan E.
Nagarsekar, Ashish C.
Cowan, Mark
Potla, Ratnakar
Sun, Junfeng
Cai, Rongman
Logun, Carolea
Shelhamer, James
Todd, Nevins W.
Singh, Ishwar S.
Luzina, Irina G.
Atamas, Sergei P.
Hasday, Jeffrey D.
TI Activation of heat shock response augments fibroblast growth factor-1
expression in wounded lung epithelium
SO AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY
LA English
DT Article
DE fibroblast growth factor-1; heat shock factor-1; epithelial wound
healing; idiopathic pulmonary fibrosis; heat shock
ID IDIOPATHIC PULMONARY-FIBROSIS; FACTOR MESSENGER-RNA; KAPPA-B-ALPHA;
ACUTE EXACERBATION; PROTEIN INDUCTION; CELL-MIGRATION; A549 CELLS;
HYPERTHERMIA; MECHANISMS; APOPTOSIS
AB We previously showed that coincident exposure to heat shock (HS; 42 degrees C for 2 h) and TNF-alpha synergistically induces apoptosis in mouse lung epithelium. We extended this work by analyzing HS effects on human lung epithelial responses to clinically relevant injury. Cotreatment with TNF-alpha and HS induced little caspase-3 and poly(ADP-ribose) polymerase cleavage in human small airway epithelial cells, A549 cells, and BEAS2B cells. Scratch wound closure rates almost doubled when A549 and BEAS2B cells and air-liquid interface cultures of human bronchial epithelial cells were heat shocked immediately after wounding. Microarray, qRT-PCR, and immunoblotting showed fibroblast growth factor 1 (FGF1) to be synergistically induced by HS and wounding. Enhanced FGF1 expression in HS/wounded A549 was blocked by inhibitors of p38 MAPK (SB203580) or HS factor (HSF)-1 (KNK-437) and in HSF1 knockout BEAS2B cells. PCR demonstrated FGF1 to be expressed from the two most distal promoters in wounded/HS cells. Wound closure in HS A549 and BEAS2B cells was reduced by FGF receptor-1/3 inhibition (SU-5402) or FGF1 depletion. Exogenous FGF1 accelerated A549 wound closure in the absence but not presence of HS. In the presence of exogenous FGF1, HS slowed wound closure, suggesting that it increases FGF1 expression but impairs FGF1-stimulated wound closure. Frozen sections from normal and idiopathic pulmonary fibrosis (IPF) lung were analyzed for FGF1 and HSP70 by immunofluorescence confocal microscopy and qRT-PCR. FGF1 and HSP70 mRNA levels were 7.5 and 5.9-fold higher in IPF than normal lung, and the proteins colocalized to fibroblastic foci in IPF lung. We conclude that HS signaling may have an important impact on gene expression contributing to lung injury, healing, and fibrosis.
C1 [Scheraga, Rachel G.; Tulapurkar, Mohan E.; Nagarsekar, Ashish C.; Cowan, Mark; Potla, Ratnakar; Todd, Nevins W.; Singh, Ishwar S.; Hasday, Jeffrey D.] Univ Maryland, Sch Med, Dept Med, Div Pulm & Crit Care Med, Baltimore, MD 21201 USA.
[Luzina, Irina G.; Atamas, Sergei P.] Univ Maryland, Sch Med, Dept Med, Div Rheumatol, Baltimore, MD 21201 USA.
[Cowan, Mark; Todd, Nevins W.; Singh, Ishwar S.; Luzina, Irina G.; Atamas, Sergei P.; Hasday, Jeffrey D.] Baltimore Vet Affairs Med Care Syst, Med & Res Serv, Baltimore, MD USA.
[Thompson, Christopher] Loyola Univ Maryland, Dept Biol, Baltimore, MD USA.
[Scheraga, Rachel G.; Sun, Junfeng; Cai, Rongman; Logun, Carolea; Shelhamer, James] NHLBI, Crit Care Sect, Bldg 10, Bethesda, MD 20892 USA.
RP Hasday, JD (reprint author), Univ Maryland, Sch Med, Hlth Sci Facil 2, Rm S347,20 Penn St, Baltimore, MD 21201 USA.
EM jhasday@umaryland.edu
FU NIH [R01HL69057]; VA Merit Review grant [IBX002143A]
FX This work was supported by NIH grant R01HL69057 and VA Merit Review
grant IBX002143A.
NR 76
TC 0
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U1 1
U2 1
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 1040-0605
EI 1522-1504
J9 AM J PHYSIOL-LUNG C
JI Am. J. Physiol.-Lung Cell. Mol. Physiol.
PD NOV 1
PY 2016
VL 311
IS 5
BP L941
EP L955
DI 10.1152/ajplung.00262.2016
PG 15
WC Physiology; Respiratory System
SC Physiology; Respiratory System
GA EE5IS
UT WOS:000389640700012
PM 27638903
ER
PT J
AU Bologna, M
Paparella, G
Fabbrini, A
Leodori, G
Rocchi, L
Hallett, M
Berardelli, A
AF Bologna, Matteo
Paparella, Giulia
Fabbrini, Andrea
Leodori, Giorgio
Rocchi, Lorenzo
Hallett, Mark
Berardelli, Alfredo
TI Effects of cerebellar theta-burst stimulation on arm and neck movement
kinematics in patients with focal dystonia
SO CLINICAL NEUROPHYSIOLOGY
LA English
DT Article
DE Transcranial magnetic stimulation; Dystonia; Cerebellum; Motor control
ID TRANSCRANIAL MAGNETIC STIMULATION; TOXIN TYPE-A; CERVICAL DYSTONIA;
WRITERS CRAMP; MOTOR CORTEX; HAND DYSTONIA; BASAL GANGLIA; EXCITABILITY;
CIRCUITS; CONNECTIVITY
AB Objective: To investigate the cerebellar inhibitory influence on the primary motor cortex in patients with focal dystonia using a cerebellar continuous theta-burst stimulation protocol (cTBS) and to evaluate any relationship with movement abnormalities.
Methods: Thirteen patients with focal hand dystonia, 13 patients with cervical dystonia and 13 healthy subjects underwent two sessions: (i) cTBS over the cerebellar hemisphere (real cTBS) and (ii) cTBS over the neck muscles (sham cTBS). The effects of cerebellar cTBS were quantified as excitability changes in the contralateral primary motor cortex, as well as possible changes in arm and neck movements in patients.
Results: Real cerebellar cTBS reduced the excitability in the contralateral primary motor cortex in healthy subjects and in patients with cervical dystonia, though not in patients with focal hand dystonia. There was no correlation between changes in primary motor cortex excitability and arm and neck movement kinematics in patients. There were no changes in clinical scores or in kinematic measures, after either real or sham cerebellar cTBS in patients.
Conclusions: The reduced cerebellar inhibitory modulation of primary motor cortex excitability in focal dystonia may be related to the body areas affected by dystonia as opposed to being a widespread pathophysiological abnormality.
Significance: The present study yields information on the differential role played by the cerebellum in the pathophysiology of different focal dystonias. (C) 2016 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.
C1 [Bologna, Matteo; Paparella, Giulia; Fabbrini, Andrea; Leodori, Giorgio; Rocchi, Lorenzo; Berardelli, Alfredo] Sapienza Univ Rome, Dept Neurol & Psychiat, Rome, Italy.
[Bologna, Matteo; Berardelli, Alfredo] Neuromed Inst IRCCS, Pozzilli, IS, Italy.
[Hallett, Mark] NINDS, Human Motor Control Sect, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
RP Berardelli, A (reprint author), Sapienza Univ Rome, Dept Neurol & Psychiat, Neuromed Inst, Viale Univ 30, I-00185 Rome, Italy.
EM alfredo.berardelli@uniroma1.it
FU Office of Rare Diseases Research at the National Center for Advancing
Translational Sciences (NCATS) [U54 TR01456]; National Institute of
Neurological Disorders and Stroke (NINDS) from the NIH [U54 NS065701];
NINDS Intramural Program
FX This study was funded in part by grants to the Dystonia Coalition from
the Office of Rare Diseases Research at the National Center for
Advancing Translational Sciences (NCATS U54 TR01456) and the National
Institute of Neurological Disorders and Stroke (NINDS U54 NS065701) from
the NIH. Dr. Hallett is supported by the NINDS Intramural Program.
NR 54
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U1 1
U2 1
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 1388-2457
EI 1872-8952
J9 CLIN NEUROPHYSIOL
JI Clin. Neurophysiol.
PD NOV
PY 2016
VL 127
IS 11
BP 3472
EP 3479
DI 10.1016/j.clinph.2016.09.008
PG 8
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA EE3QO
UT WOS:000389510200009
PM 27721106
ER
PT J
AU Coble, MD
Buckleton, J
Butler, JM
Egeland, T
Fimmers, R
Gill, P
Gusmao, L
Guttman, B
Krawczak, M
Morling, N
Parson, W
Pinto, N
Schneider, PM
Sherry, ST
Willuweit, S
Prinz, M
AF Coble, M. D.
Buckleton, J.
Butler, J. M.
Egeland, T.
Fimmers, R.
Gill, P.
Gusmao, L.
Guttman, B.
Krawczak, M.
Morling, N.
Parson, W.
Pinto, N.
Schneider, P. M.
Sherry, S. T.
Willuweit, S.
Prinz, M.
TI DNA Commission of the International Society for Forensic Genetics:
Recommendations on the validation of software programs performing
biostatistical calculations for forensic genetics applications
SO FORENSIC SCIENCE INTERNATIONAL-GENETICS
LA English
DT Article
DE Biostatistical software; Software validation; Validation and
verification; Forensic genetics; Software training and testing
ID LIKELIHOOD RATIOS; DROP-OUT; PROFILES; PROPOSITIONS; PATERNITY; MIXTURE;
MODELS
AB The use of biostatistical software programs to assist in data interpretation and calculate likelihood ratios is essential to forensic geneticists and part of the daily case work flow for both kinship and DNA identification laboratories. Previous recommendations issued by the DNA Commission of the International Society for Forensic Genetics (ISFG) covered the application of bio-statistical evaluations for STR typing results in identification and kinship cases, and this is now being expanded to provide best practices regarding validation and verification of the software required for these calculations. With larger multiplexes, more complex mixtures, and increasing requests for extended family testing, laboratories are relying more than ever on specific software solutions and sufficient validation, training and extensive documentation are of upmost importance.
Here, we present recommendations for the minimum requirements to validate bio-statistical software to be used in forensic genetics. We distinguish between developmental validation and the responsibilities of the software developer or provider, and the internal validation studies to be performed by the end user. Recommendations for the software provider address, for example, the documentation of the underlying models used by the software, validation data expectations, version control, implementation and training support, as well as continuity and user notifications. For the internal validations the recommendations include: creating a validation plan, requirements for the range of samples to be tested, Standard Operating Procedure development, and internal laboratory training and education. To ensure that all laboratories have access to a wide range of samples for validation and training purposes the ISFG DNA commission encourages collaborative studies and public repositories of STR typing results. Published by Elsevier Ireland Ltd.
C1 [Coble, M. D.] Natl Inst Stand & Technol, Appl Genet Grp, 100 Bur Dr MS 8314, Gaithersburg, MD 20899 USA.
[Buckleton, J.] ESR, Private Bag 92021, Auckland 1142, New Zealand.
[Buckleton, J.] Natl Inst Stand & Technol, Stat Engn Div Guest Researcher, Gaithersburg, MD 20899 USA.
[Butler, J. M.] Natl Inst Stand & Technol, Special Programs Off, Gaithersburg, MD 20899 USA.
[Egeland, T.] Norwegian Univ Life Sci, Oslo, Norway.
[Fimmers, R.] Univ Bonn, Inst Med Stat Informat & Epidemiol, Bonn, Germany.
[Gill, P.] Norwegian Inst Publ Hlth, Oslo, Norway.
[Gill, P.] Univ Oslo, Oslo, Norway.
[Gusmao, L.] State Univ Rio de Janeiro UERJ, Rio De Janeiro, Brazil.
[Gusmao, L.; Pinto, N.] Univ Porto, Inst Mol Pathol & Immunol, IPATIMUP, Rua Campo Alegre 823, P-4100 Oporto, Portugal.
[Gusmao, L.; Pinto, N.] Univ Porto, Inst Invest & Inovacao Saude, Rua Campo Alegre 823, P-4100 Oporto, Portugal.
[Guttman, B.] Natl Inst Stand & Technol, Software & Syst Div, Gaithersburg, MD 20899 USA.
[Krawczak, M.] Christian Albrechts Univ Kiel, Inst Med Informat & Stat, Kiel, Germany.
[Morling, N.] Univ Copenhagen, Fac Hlth & Med Sci, Dept Forens Med, Sect Forens Genet, DK-1168 Copenhagen, Denmark.
[Parson, W.] Med Univ Innsbruck, Inst Legal Med, Innsbruck, Austria.
[Parson, W.] Penn State Univ, Forens Sci Program, University Pk, PA 16802 USA.
[Pinto, N.] Univ Porto, Inst Res & Innovat Hlth I3S, Oporto, Portugal.
[Pinto, N.] Univ Porto, Ctr Math, Oporto, Portugal.
[Schneider, P. M.] Univ Cologne, Fac Med, Inst Legal Med, Cologne, Germany.
[Sherry, S. T.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bldg 10, Bethesda, MD 20892 USA.
[Willuweit, S.] Charite, Inst Legal Med & Forens Sci, Dept Forens Genet, Berlin, Germany.
[Prinz, M.] John Jay Coll Criminal Justice, New York, NY USA.
RP Coble, MD (reprint author), Natl Inst Stand & Technol, Appl Genet Grp, 100 Bur Dr MS 8314, Gaithersburg, MD 20899 USA.
EM mcoble@nist.gov
RI Gusmao, Leonor/B-3122-2013; Krawczak, Michael/A-8964-2010
OI Gusmao, Leonor/0000-0003-0432-6481; Krawczak,
Michael/0000-0003-2603-1502
NR 34
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U1 2
U2 2
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 1872-4973
EI 1878-0326
J9 FORENSIC SCI INT-GEN
JI Forensic Sci. Int.-Genet.
PD NOV
PY 2016
VL 25
BP 191
EP 197
DI 10.1016/j.fsigen.2016.09.002
PG 7
WC Genetics & Heredity; Medicine, Legal
SC Genetics & Heredity; Legal Medicine
GA EE3YX
UT WOS:000389539600033
PM 27643465
ER
PT J
AU Quang, T
Schwarz, RA
Dawsey, SM
Tan, MC
Patel, K
Yu, XY
Wang, GQ
Zhang, F
Xu, H
Anandasabapathy, S
Richards-Kortum, R
AF Quang, Timothy
Schwarz, Richard A.
Dawsey, Sanford M.
Tan, Mimi C.
Patel, Kalpesh
Yu, Xinying
Wang, Guiqi
Zhang, Fan
Xu, Hong
Anandasabapathy, Sharmila
Richards-Kortum, Rebecca
TI A tablet-interfaced high-resolution microendoscope with automated image
interpretation for real-time evaluation of esophageal squamous cell
neoplasia
SO GASTROINTESTINAL ENDOSCOPY
LA English
DT Article
ID LOW-COST; CARCINOMA; CANCER; EPIDEMIOLOGY; DIAGNOSIS; DYSPLASIA; REGION;
TRIAL; CHINA; RISK
AB Background and Aims: In recent years high-resolution microendoscopy (HRME) has shown potential to improve screening for esophageal squamous cell neoplasia. Furthering its utility in a clinical setting, especially in lower-resource settings, could be accomplished by reducing the size and cost of the system as well as incorporating the ability of real-time, objective feedback. This article describes a tablet-interfaced HRME with fully automated, real-time image analysis.
Methods: The performance of the tablet-interfaced HRME was assessed by acquiring images from the oral mucosa in a normal volunteer. An automated, real-time analysis algorithm was developed and evaluated using training, test, and validation images from a previous in vivo study of 177 patients referred for screening or surveillance endoscopy in China. The algorithm was then implemented in a tablet HRME that was used to obtain and analyze images from esophageal tissue in 3 patients. Images were displayed alongside the probability that the imaged region was neoplastic.
Results: The tablet-interfaced HRME demonstrated comparable imaging performance at a lower cost compared with first-generation laptop-interfaced HRME systems. In a post-hoc quantitative analysis, the algorithm identified neoplasia with a sensitivity and specificity of 95% and 91%, respectively, in the validation set compared with 84% and 95% achieved in the original study.
Conclusions: The tablet-based HRME is a low-cost tool that provides quantitative diagnostic information to the endoscopist in real time. This could be especially beneficial in lower-resource settings for operators with less experience interpreting HRME images.
C1 [Quang, Timothy; Schwarz, Richard A.; Richards-Kortum, Rebecca] Rice Univ, Dept Bioengn, 6500 Main St, Houston, TX 77030 USA.
[Dawsey, Sanford M.] NCI, Dept Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Tan, Mimi C.; Patel, Kalpesh; Anandasabapathy, Sharmila] Baylor Coll Med, Dept Gastroenterol, Houston, TX 77030 USA.
[Yu, Xinying; Wang, Guiqi] Chinese Acad Med Sci, Canc Inst & Hosp, Dept Endoscopy, Beijing, Peoples R China.
[Zhang, Fan; Xu, Hong] Jilin Univ, Hosp 1, Dept Gastrointestinal Med, Changchun, Jilin, Peoples R China.
RP Quang, T (reprint author), Rice Univ, Dept Bioengn, 6500 Main St, Houston, TX 77030 USA.
FU Remicalm; National Cancer Institute of the National Institutes of Health
[R01CA181275]
FX The following authors disclosed financial relationships relevant to this
publication: R. Richards-Kortum: Licensing fees recipient for IP
licensed from the University of Texas from Remicalm. All other authors
disclosed no financial relationships relevant to this publication.
Research support for this study was provided by the National Cancer
Institute of the National Institutes of Health under Award Number
R01CA181275. The content is solely the responsibility of the authors and
does not necessarily represent the official views of the National
Institutes of Health.
NR 17
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U1 2
U2 2
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0016-5107
EI 1097-6779
J9 GASTROINTEST ENDOSC
JI Gastrointest. Endosc.
PD NOV
PY 2016
VL 84
IS 5
BP 834
EP 841
DI 10.1016/j.gie.2016.03.1472
PG 8
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA EE4AK
UT WOS:000389543800015
PM 27036635
ER
PT J
AU Lin, J
Kelley-Moore, J
AF Lin, J.
Kelley-Moore, J.
TI NEW DIMENSIONS OF INEQUALITY: INTER-INDIVIDUAL VARIABILITY IN FUNCTIONAL
LIMITATIONS BY RACE/GENDER
SO GERONTOLOGIST
LA English
DT Meeting Abstract
C1 [Lin, J.] NIH, Bldg 10, Bethesda, MD 20892 USA.
[Kelley-Moore, J.] Case Western Reserve Univ, Cleveland, OH 44106 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0016-9013
EI 1758-5341
J9 GERONTOLOGIST
JI Gerontologist
PD NOV
PY 2016
VL 56
SU 3
BP 22
EP 22
PG 1
WC Gerontology
SC Geriatrics & Gerontology
GA ED1DT
UT WOS:000388585000087
ER
PT J
AU Agha, G
Joehanes, R
Levy, D
Baccarelli, A
AF Agha, G.
Joehanes, R.
Levy, D.
Baccarelli, A.
TI DNA METHYLATION IS ASSOCIATED WITH INCIDENT CARDIOVASCULAR DISEASE
SO GERONTOLOGIST
LA English
DT Meeting Abstract
C1 [Agha, G.; Baccarelli, A.] Harvard TH Chan Sch Publ Hlth, Boston, MA USA.
[Joehanes, R.] Hebrew SeniorLife, Boston, MA USA.
[Levy, D.] NHLBI, Bldg 10, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0016-9013
EI 1758-5341
J9 GERONTOLOGIST
JI Gerontologist
PD NOV
PY 2016
VL 56
SU 3
BP 35
EP 35
PG 1
WC Gerontology
SC Geriatrics & Gerontology
GA ED1DT
UT WOS:000388585000136
ER
PT J
AU Levine, ME
Hosgood, HD
Chen, B
Absher, D
Assimes, T
Horvath, S
AF Levine, M. E.
Hosgood, H. D.
Chen, B.
Absher, D.
Assimes, T.
Horvath, S.
TI DNA METHYLATION AGE OF BLOOD PREDICTS ONSET OF LUNG CANCER IN THE
WOMEN'S HEALTH INITIATIVE
SO GERONTOLOGIST
LA English
DT Meeting Abstract
C1 [Levine, M. E.] Univ Calif Los Angeles, Los Angeles, CA USA.
[Chen, B.] NIA, Bethesda, MD 20892 USA.
[Absher, D.] Hudson Alpha Inst Biotechnol, Huntsville, AL USA.
[Assimes, T.] Standford Univ, Sch Med, Stanford, CA USA.
[Horvath, S.] David Geffen Sch Med, Los Angeles, CA USA.
[Hosgood, H. D.] Albert Einstein Coll Med, Bronx, NY 10467 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0016-9013
EI 1758-5341
J9 GERONTOLOGIST
JI Gerontologist
PD NOV
PY 2016
VL 56
SU 3
BP 35
EP 36
PG 2
WC Gerontology
SC Geriatrics & Gerontology
GA ED1DT
UT WOS:000388585000137
ER
PT J
AU Murabito, JM
Rong, J
Lunetta, K
Tanriverdi, K
Freedman, J
Levy, D
Larson, MG
AF Murabito, J. M.
Rong, J.
Lunetta, K.
Tanriverdi, K.
Freedman, J.
Levy, D.
Larson, M. G.
TI RELATIONS BETWEEN MICRORNA EXPRESSION IN BLOOD AND HAND GRIP STRENGTH IN
A COMMUNITY SAMPLE
SO GERONTOLOGIST
LA English
DT Meeting Abstract
C1 [Murabito, J. M.] Boston Univ, Sch Med, Gen Internal Med Sect, Med, Framingham, MA USA.
[Rong, J.] Framingham Heart Dis Epidemiol Study, Framingham, MA USA.
[Lunetta, K.; Larson, M. G.] Boston Univ, Sch Publ Hlth, Boston, MA USA.
[Tanriverdi, K.; Freedman, J.] Univ Massachusetts, Sch Med, Worcester, MA USA.
[Levy, D.] NHLBI, Bldg 10, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0016-9013
EI 1758-5341
J9 GERONTOLOGIST
JI Gerontologist
PD NOV
PY 2016
VL 56
SU 3
BP 36
EP 36
PG 1
WC Gerontology
SC Geriatrics & Gerontology
GA ED1DT
UT WOS:000388585000138
ER
PT J
AU Koehly, L
AF Koehly, L.
TI IT'S INTER-PERSONAL: FAMILY RELATIONSHIPS, GENETIC RISK, AND CAREGIVING
SO GERONTOLOGIST
LA English
DT Meeting Abstract
C1 [Koehly, L.] NHGRI, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0016-9013
EI 1758-5341
J9 GERONTOLOGIST
JI Gerontologist
PD NOV
PY 2016
VL 56
SU 3
BP 39
EP 39
PG 1
WC Gerontology
SC Geriatrics & Gerontology
GA ED1DT
UT WOS:000388585000147
ER
PT J
AU Smith, C
Morgan, L
Evans, MK
Zonderman, AB
AF Smith, C.
Morgan, L.
Evans, M. K.
Zonderman, A. B.
TI LIFETIME USE OF ILLICIT DRUGS IN AN URBAN SAMPLE OF MIDDLE-AGED ADULTS
SO GERONTOLOGIST
LA English
DT Meeting Abstract
C1 [Smith, C.; Morgan, L.] UMBC, Baltimore, MD USA.
[Evans, M. K.; Zonderman, A. B.] NIA, Baltimore, MD 21224 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0016-9013
EI 1758-5341
J9 GERONTOLOGIST
JI Gerontologist
PD NOV
PY 2016
VL 56
SU 3
BP 79
EP 80
PG 2
WC Gerontology
SC Geriatrics & Gerontology
GA ED1DT
UT WOS:000388585000288
ER
PT J
AU Sutphin, GL
Backer, G
Sheehan, S
Murabito, JM
Johnson, A
Korstanje, R
AF Sutphin, G. L.
Backer, G.
Sheehan, S.
Murabito, J. M.
Johnson, A.
Korstanje, R.
TI KYNURENINE PATHWAY GENES INFLUENCE AGING THROUGH MULTIPLE DISTINCT
MOLECULAR MECHANISMS
SO GERONTOLOGIST
LA English
DT Meeting Abstract
C1 [Sutphin, G. L.; Backer, G.; Sheehan, S.; Korstanje, R.] Jackson Lab, 600 Main St, Bar Harbor, ME 04609 USA.
[Murabito, J. M.] Boston Univ, Sch Med, Sect Gen Med, Boston, MA 02118 USA.
[Murabito, J. M.; Johnson, A.] NHLBI, Framingham Heart Study, Framingham, MA USA.
[Johnson, A.] NHLBI, Populat Sci Branch, Bldg 10, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0016-9013
EI 1758-5341
J9 GERONTOLOGIST
JI Gerontologist
PD NOV
PY 2016
VL 56
SU 3
BP 110
EP 111
PG 2
WC Gerontology
SC Geriatrics & Gerontology
GA ED1DT
UT WOS:000388585000398
ER
PT J
AU Elliott, C
AF Elliott, C.
TI NATIONAL INSTITUTE ON AGING - DIVISION OF NEUROSCIENCE
SO GERONTOLOGIST
LA English
DT Meeting Abstract
C1 [Elliott, C.] NIA, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0016-9013
EI 1758-5341
J9 GERONTOLOGIST
JI Gerontologist
PD NOV
PY 2016
VL 56
SU 3
BP 131
EP 131
PG 1
WC Gerontology
SC Geriatrics & Gerontology
GA ED1DT
UT WOS:000388585000487
ER
PT J
AU Hill, C
Elliott, C
AF Hill, C.
Elliott, C.
TI HEALTH DISPARITIES RESEARCH WITH THE NATIONAL INSTITUTE ON AGING (NIA)
SO GERONTOLOGIST
LA English
DT Meeting Abstract
C1 [Hill, C.; Elliott, C.] NIA, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0016-9013
EI 1758-5341
J9 GERONTOLOGIST
JI Gerontologist
PD NOV
PY 2016
VL 56
SU 3
BP 131
EP 131
PG 1
WC Gerontology
SC Geriatrics & Gerontology
GA ED1DT
UT WOS:000388585000486
ER
PT J
AU Joseph, L
AF Joseph, L.
TI GERIATRICS AND CLINICAL GERONTOLOGY'S APPROACHES FOR ADDRESSING HEALTH
DISPARITIES
SO GERONTOLOGIST
LA English
DT Meeting Abstract
C1 [Joseph, L.] NIA, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0016-9013
EI 1758-5341
J9 GERONTOLOGIST
JI Gerontologist
PD NOV
PY 2016
VL 56
SU 3
BP 131
EP 131
PG 1
WC Gerontology
SC Geriatrics & Gerontology
GA ED1DT
UT WOS:000388585000488
ER
PT J
AU Nielsen, L
AF Nielsen, L.
TI HEALTH DISPARITIES RESEARCH AND PRIORITIES IN THE NIA DIVISION OF
BEHAVIORAL AND SOCIAL RESEARCH
SO GERONTOLOGIST
LA English
DT Meeting Abstract
C1 [Nielsen, L.] NIA, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0016-9013
EI 1758-5341
J9 GERONTOLOGIST
JI Gerontologist
PD NOV
PY 2016
VL 56
SU 3
BP 131
EP 131
PG 1
WC Gerontology
SC Geriatrics & Gerontology
GA ED1DT
UT WOS:000388585000489
ER
PT J
AU Sierra, F
AF Sierra, F.
TI HEALTH DISPARITIES RESEARCH AT NIA'S DIVISION OF AGING BIOLOGY
SO GERONTOLOGIST
LA English
DT Meeting Abstract
C1 [Sierra, F.] NIA, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0016-9013
EI 1758-5341
J9 GERONTOLOGIST
JI Gerontologist
PD NOV
PY 2016
VL 56
SU 3
BP 131
EP 131
PG 1
WC Gerontology
SC Geriatrics & Gerontology
GA ED1DT
UT WOS:000388585000490
ER
PT J
AU Salimi, S
Shardell, M
Huang, Y
Gruber-Baldini, A
Miller, R
Guralnik, J
Orwig, D
Magaziner, J
AF Salimi, S.
Shardell, M.
Huang, Y.
Gruber-Baldini, A.
Miller, R.
Guralnik, J.
Orwig, D.
Magaziner, J.
TI TNFAR-1 AND FRAILTY IN MEN AND WOMEN AFTER HIP FRACTURE: FINDINGS FROM
THE BALTIMORE HIP STUDIES
SO GERONTOLOGIST
LA English
DT Meeting Abstract
C1 [Salimi, S.; Shardell, M.; Gruber-Baldini, A.; Guralnik, J.; Orwig, D.; Magaziner, J.] Univ Maryland, Sch Med, Dept Epidemiol & Publ Hlth, Baltimore, MD 21201 USA.
[Salimi, S.; Shardell, M.] NIA, NIH, Baltimore, MD 21224 USA.
[Huang, Y.] Univ Maryland, Dept Math & Stat, Baltimore, MD 21201 USA.
[Miller, R.] Novartis Inst Biomed Res, Cambridge, MA USA.
[Miller, R.] Novartis Inst Biomed Res, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0016-9013
EI 1758-5341
J9 GERONTOLOGIST
JI Gerontologist
PD NOV
PY 2016
VL 56
SU 3
BP 177
EP 177
PG 1
WC Gerontology
SC Geriatrics & Gerontology
GA ED1DT
UT WOS:000388585000649
ER
PT J
AU Kane, AE
Mitchell, S
Mach, J
Huizer-Pajkos, A
Cogger, V
Le Couteur, D
De Cabo, R
Hilmer, S
AF Kane, A. E.
Mitchell, S.
Mach, J.
Huizer-Pajkos, A.
Cogger, V.
Le Couteur, D.
De Cabo, R.
Hilmer, S.
TI ACETAMINOPHEN HEPATOTOXICITY IN MICE: EFFECT OF AGE, FRAILTY AND
EXPOSURE TYPE
SO GERONTOLOGIST
LA English
DT Meeting Abstract
C1 [Kane, A. E.; Mach, J.; Huizer-Pajkos, A.; Hilmer, S.] Kolling Inst, St Leonards, NSW, Australia.
[Kane, A. E.; Mach, J.; Cogger, V.; Le Couteur, D.; Hilmer, S.] Univ Sydney, Sydney, NSW, Australia.
[Kane, A. E.; Mach, J.; Huizer-Pajkos, A.; Hilmer, S.] Royal North Shore Hosp, St Leonards, NSW, Australia.
[Mitchell, S.; De Cabo, R.] NIA, Baltimore, MD 21224 USA.
[Cogger, V.; Le Couteur, D.] ANZAC Res Inst, Concord, NSW, Australia.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0016-9013
EI 1758-5341
J9 GERONTOLOGIST
JI Gerontologist
PD NOV
PY 2016
VL 56
SU 3
BP 180
EP 180
PG 1
WC Gerontology
SC Geriatrics & Gerontology
GA ED1DT
UT WOS:000388585000658
ER
PT J
AU Strotmeyer, ES
Boudreau, RM
Minion, SC
Cauley, JA
Donohue, JM
Harris, TB
Newman, AB
Waters, TM
AF Strotmeyer, E. S.
Boudreau, R. M.
Minion, S. C.
Cauley, J. A.
Donohue, J. M.
Harris, T. B.
Newman, A. B.
Waters, T. M.
TI SENSORY NERVE IMPAIRMENT IS ASSOCIATED WITH HIGHER TOTAL MEDICARE COSTS:
THE HEALTH ABC STUDY
SO GERONTOLOGIST
LA English
DT Meeting Abstract
C1 [Strotmeyer, E. S.; Boudreau, R. M.; Minion, S. C.; Cauley, J. A.; Donohue, J. M.; Newman, A. B.] Univ Pittsburgh, Pittsburgh, PA USA.
[Harris, T. B.] NIA, Bethesda, MD 20892 USA.
[Waters, T. M.] Univ Tennessee, Memphis, TN USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0016-9013
EI 1758-5341
J9 GERONTOLOGIST
JI Gerontologist
PD NOV
PY 2016
VL 56
SU 3
BP 216
EP 217
PG 2
WC Gerontology
SC Geriatrics & Gerontology
GA ED1DT
UT WOS:000388585001043
ER
PT J
AU ChilesShaffer, N
Simonsick, E
Studenski, S
AF ChilesShaffer, N.
Simonsick, E.
Studenski, S.
TI FAT MASS PREDICTS GAIT SPEED DECLINE EXCEPT IN THOSE OVER 80
SO GERONTOLOGIST
LA English
DT Meeting Abstract
C1 [ChilesShaffer, N.; Simonsick, E.; Studenski, S.] NIA, Baltimore, MD 21224 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0016-9013
EI 1758-5341
J9 GERONTOLOGIST
JI Gerontologist
PD NOV
PY 2016
VL 56
SU 3
BP 218
EP 219
PG 2
WC Gerontology
SC Geriatrics & Gerontology
GA ED1DT
UT WOS:000388585001052
ER
PT J
AU Ko, S
Jerome, G
Simonsick, EM
Studenski, S
Hausdorff, JM
Ferrucci, L
AF Ko, S.
Jerome, G.
Simonsick, E. M.
Studenski, S.
Hausdorff, J. M.
Ferrucci, L.
TI DUAL-TASK-WALK PERFORMANCE AND USUAL GAIT PATTERNS IN HEALTHY OLDER
ADULTS RESULTS FROM THE BLSA
SO GERONTOLOGIST
LA English
DT Meeting Abstract
C1 [Ko, S.] Chonnam Natl Univ, Yeosu, South Korea.
[Jerome, G.] Towson Univ, Towson, MD USA.
[Simonsick, E. M.; Studenski, S.; Ferrucci, L.] NIA, NIH, Baltimore, MD 21224 USA.
[Hausdorff, J. M.] Tel Aviv Sourasky Med Ctr, Dept Neurol, Tel Aviv, Israel.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0016-9013
EI 1758-5341
J9 GERONTOLOGIST
JI Gerontologist
PD NOV
PY 2016
VL 56
SU 3
BP 218
EP 218
PG 1
WC Gerontology
SC Geriatrics & Gerontology
GA ED1DT
UT WOS:000388585001051
ER
PT J
AU Tian, Q
Resnick, SM
Bilgel, M
Wong, DF
Ferrucci, L
Studenski, S
AF Tian, Q.
Resnick, S. M.
Bilgel, M.
Wong, D. F.
Ferrucci, L.
Studenski, S.
TI beta-AMYLOID BURDEN PREDICTS LOWER EXTREMITY PERFORMANCE DECLINE IN
COGNITIVELY NORMAL OLDER ADULTS
SO GERONTOLOGIST
LA English
DT Meeting Abstract
C1 [Tian, Q.; Resnick, S. M.; Bilgel, M.; Ferrucci, L.; Studenski, S.] NIA, Translat Gerontol Branch, Baltimore, MD 21224 USA.
[Wong, D. F.] Johns Hopkins Med, Baltimore, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0016-9013
EI 1758-5341
J9 GERONTOLOGIST
JI Gerontologist
PD NOV
PY 2016
VL 56
SU 3
BP 218
EP 218
PG 1
WC Gerontology
SC Geriatrics & Gerontology
GA ED1DT
UT WOS:000388585001050
ER
PT J
AU Simonsick, EM
Meier, H
ChilesShaffer, N
Studenski, S
Ferrucci, L
AF Simonsick, E. M.
Meier, H.
ChilesShaffer, N.
Studenski, S.
Ferrucci, L.
TI CORE BODY TEMPERATURE AS A BIOMARKER OF ENERGETIC EFFICIENCY AND
MOBILITY PERFORMANCE
SO GERONTOLOGIST
LA English
DT Meeting Abstract
C1 [Simonsick, E. M.; ChilesShaffer, N.; Studenski, S.; Ferrucci, L.] NIA, Intramural Res Program, Baltimore, MD 21224 USA.
[Meier, H.] NIEHS, Durham, NC USA.
NR 0
TC 0
Z9 0
U1 2
U2 2
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0016-9013
EI 1758-5341
J9 GERONTOLOGIST
JI Gerontologist
PD NOV
PY 2016
VL 56
SU 3
BP 219
EP 219
PG 1
WC Gerontology
SC Geriatrics & Gerontology
GA ED1DT
UT WOS:000388585001053
ER
PT J
AU Schrack, J
Simonsick, E
Studenski, S
Ferrucci, L
AF Schrack, J.
Simonsick, E.
Studenski, S.
Ferrucci, L.
TI DECLINING WALKING EFFICIENCY PREDICTS GREATER PERCEIVED FATIGABILITY
WITH AGING
SO GERONTOLOGIST
LA English
DT Meeting Abstract
C1 [Schrack, J.] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA.
[Simonsick, E.; Studenski, S.; Ferrucci, L.] NIA, Baltimore, MD 21224 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0016-9013
EI 1758-5341
J9 GERONTOLOGIST
JI Gerontologist
PD NOV
PY 2016
VL 56
SU 3
BP 240
EP 241
PG 2
WC Gerontology
SC Geriatrics & Gerontology
GA ED1DT
UT WOS:000388585001141
ER
PT J
AU Santanasto, AJ
Newman, AB
Strotmeyer, ES
Caserotti, P
Harris, TB
Simonsick, E
Glynn, NW
AF Santanasto, A. J.
Newman, A. B.
Strotmeyer, E. S.
Caserotti, P.
Harris, T. B.
Simonsick, E.
Glynn, N. W.
TI RELATIONSHIP BETWEEN FAT MASS AND FATIGABILITY IN OLDER ADULTS
SO GERONTOLOGIST
LA English
DT Meeting Abstract
C1 [Santanasto, A. J.; Newman, A. B.; Strotmeyer, E. S.; Glynn, N. W.] Univ Pittsburgh, Pittsburgh, PA USA.
[Caserotti, P.] Univ Southern Denmark, Odense, Denmark.
[Harris, T. B.; Simonsick, E.] NIA, Baltimore, MD 21224 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0016-9013
EI 1758-5341
J9 GERONTOLOGIST
JI Gerontologist
PD NOV
PY 2016
VL 56
SU 3
BP 241
EP 241
PG 1
WC Gerontology
SC Geriatrics & Gerontology
GA ED1DT
UT WOS:000388585001143
ER
PT J
AU Simonsick, EM
Jerome, G
Nicklas, B
Schrack, J
Studenski, S
Ferrucci, L
AF Simonsick, E. M.
Jerome, G.
Nicklas, B.
Schrack, J.
Studenski, S.
Ferrucci, L.
TI THE WEIGHTINESS OF FATIGABILITY: FINDINGS FROM THE BALTIMORE
LONGITUDINAL STUDY OF AGING (BLSA)
SO GERONTOLOGIST
LA English
DT Meeting Abstract
C1 [Simonsick, E. M.; Studenski, S.; Ferrucci, L.] NIA, Intramural Res Program, Baltimore, MD 21224 USA.
[Jerome, G.] Towson Univ, Towson, MD USA.
[Nicklas, B.] Wake Forest Univ, Wake Forest, NC USA.
[Schrack, J.] Johns Hopkins Univ, Baltimore, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0016-9013
EI 1758-5341
J9 GERONTOLOGIST
JI Gerontologist
PD NOV
PY 2016
VL 56
SU 3
BP 241
EP 241
PG 1
WC Gerontology
SC Geriatrics & Gerontology
GA ED1DT
UT WOS:000388585001144
ER
PT J
AU ChilesShaffer, N
Thorpe, R
Simonsick, E
Studenski, S
AF ChilesShaffer, N.
Thorpe, R.
Simonsick, E.
Studenski, S.
TI BODY COMPOSITION DOES NOT EXPLAIN THE RELATIONSHIP BETWEEN RACE AND
PHYSICAL PERFORMANCE
SO GERONTOLOGIST
LA English
DT Meeting Abstract
C1 [ChilesShaffer, N.; Simonsick, E.; Studenski, S.] NIA, Baltimore, MD 21224 USA.
[Thorpe, R.] Johns Hopkins Sch Publ Hlth, Baltimore, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0016-9013
EI 1758-5341
J9 GERONTOLOGIST
JI Gerontologist
PD NOV
PY 2016
VL 56
SU 3
BP 242
EP 242
PG 1
WC Gerontology
SC Geriatrics & Gerontology
GA ED1DT
UT WOS:000388585001149
ER
PT J
AU Espeland, M
Crimmins, E
Grossardt, B
Harris, TB
Kritchevsky, S
Rocca, W
Temprosa, M
Barzilai, N
AF Espeland, M.
Crimmins, E.
Grossardt, B.
Harris, T. B.
Kritchevsky, S.
Rocca, W.
Temprosa, M.
Barzilai, N.
TI BENCHMARKS FOR DESIGNING CLINICAL TRIALS WITH MULTIPLE MORBIDITY
OUTCOMES
SO GERONTOLOGIST
LA English
DT Meeting Abstract
C1 [Espeland, M.; Kritchevsky, S.] Wake Forest Sch Med, Dept Biostat Sci, Winston Salem, NC USA.
[Crimmins, E.] Univ Southern Calif, Los Angeles, CA USA.
[Grossardt, B.; Rocca, W.] Mayo Clin, Rochester, MN USA.
[Harris, T. B.] NIA, Bethesda, MD 20892 USA.
[Temprosa, M.] George Washington Univ, Rockville, MD USA.
[Barzilai, N.] Albert Einstein Coll Med, Bronx, NY 10467 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0016-9013
EI 1758-5341
J9 GERONTOLOGIST
JI Gerontologist
PD NOV
PY 2016
VL 56
SU 3
BP 251
EP 252
PG 2
WC Gerontology
SC Geriatrics & Gerontology
GA ED1DT
UT WOS:000388585001185
ER
PT J
AU Mueller, M
Bures, R
Gee, NR
AF Mueller, M.
Bures, R.
Gee, N. R.
TI HUMAN-ANIMAL INTERACTION AND HEALTHY AGING: FINDINGS FROM THE 2012
HEALTH AND RETIREMENT STUDY
SO GERONTOLOGIST
LA English
DT Meeting Abstract
C1 [Gee, N. R.] WALTHAM, Melton Mobray, England.
[Mueller, M.] Tufts Univ, North Grafton, MA USA.
[Bures, R.] NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 2
U2 2
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0016-9013
EI 1758-5341
J9 GERONTOLOGIST
JI Gerontologist
PD NOV
PY 2016
VL 56
SU 3
BP 261
EP 261
PG 1
WC Gerontology
SC Geriatrics & Gerontology
GA ED1DT
UT WOS:000388585001230
ER
PT J
AU Gross, A
McAdams-DeMarco, M
Xue, Q
Carlson, M
Simonsick, EM
Bandeen-Roche, KJ
Walston, J
AF Gross, A.
McAdams-DeMarco, M.
Xue, Q.
Carlson, M.
Simonsick, E. M.
Bandeen-Roche, K. J.
Walston, J.
TI BIOLOGICAL MARKERS OF PHYSIOLOGIC DYSREGULATION AS MEASURES OF FRAILTY
SO GERONTOLOGIST
LA English
DT Meeting Abstract
C1 [Gross, A.; McAdams-DeMarco, M.; Carlson, M.; Bandeen-Roche, K. J.] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA.
[Xue, Q.; Walston, J.] Johns Hopkins Sch Med, Baltimore, MD USA.
[Simonsick, E. M.] NIA, Baltimore, MD 21224 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0016-9013
EI 1758-5341
J9 GERONTOLOGIST
JI Gerontologist
PD NOV
PY 2016
VL 56
SU 3
BP 285
EP 286
PG 2
WC Gerontology
SC Geriatrics & Gerontology
GA ED1DT
UT WOS:000388585001330
ER
PT J
AU Rosso, AL
Winger, ME
Cauley, JA
Harris, TB
Schwartz, A
Waters, TM
Yaffe, K
Strotmeyer, ES
AF Rosso, A. L.
Winger, M. E.
Cauley, J. A.
Harris, T. B.
Schwartz, A.
Waters, T. M.
Yaffe, K.
Strotmeyer, E. S.
TI COGNITIVE FUNCTION AND RISK OF FALL-RELATED FRACTURE AND NON-FRACTURE
INJURIES IN OLDER ADULTS
SO GERONTOLOGIST
LA English
DT Meeting Abstract
C1 [Rosso, A. L.; Winger, M. E.; Cauley, J. A.; Strotmeyer, E. S.] Univ Pittsburgh, Pittsburgh, PA USA.
[Harris, T. B.] NIA, Bethesda, MD 20892 USA.
[Waters, T. M.] Univ Tennessee, Ctr Hlth Sci, Memphis, TN 38163 USA.
[Yaffe, K.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0016-9013
EI 1758-5341
J9 GERONTOLOGIST
JI Gerontologist
PD NOV
PY 2016
VL 56
SU 3
BP 316
EP 316
PG 1
WC Gerontology
SC Geriatrics & Gerontology
GA ED1DT
UT WOS:000388585001458
ER
PT J
AU Tian, Q
Resnick, SM
Ferrucci, L
Studenski, S
AF Tian, Q.
Resnick, S. M.
Ferrucci, L.
Studenski, S.
TI THE TEMPORAL SEQUENCE OF COGNITION AND MOBILITY IN AGING
SO GERONTOLOGIST
LA English
DT Meeting Abstract
C1 [Tian, Q.; Resnick, S. M.; Ferrucci, L.; Studenski, S.] NIA, Translat Gerontol Branch, Baltimore, MD 21224 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0016-9013
EI 1758-5341
J9 GERONTOLOGIST
JI Gerontologist
PD NOV
PY 2016
VL 56
SU 3
BP 337
EP 337
PG 1
WC Gerontology
SC Geriatrics & Gerontology
GA ED1DT
UT WOS:000388585001534
ER
PT J
AU Kane, AE
Huizer-Pajkos, A
Mach, J
Howlett, SE
Mitchell, S
de Cabo, R
Le Couteur, D
Hilmer, S
AF Kane, A. E.
Huizer-Pajkos, A.
Mach, J.
Howlett, S. E.
Mitchell, S.
de Cabo, R.
Le Couteur, D.
Hilmer, S.
TI A COMPARISON OF TWO MOUSE FRAILTY ASSESSMENT TOOLS
SO GERONTOLOGIST
LA English
DT Meeting Abstract
C1 [Kane, A. E.; Huizer-Pajkos, A.; Mach, J.; Hilmer, S.] Kolling Inst, St Leonards, NSW, Australia.
[Kane, A. E.; Mach, J.; Le Couteur, D.; Hilmer, S.] Univ Sydney, Sydney, NSW, Australia.
[Kane, A. E.; Huizer-Pajkos, A.; Mach, J.; Hilmer, S.] Royal North Shore Hosp, St Leonards, NSW, Australia.
[Howlett, S. E.] Dalhousie Univ, Halifax, NS, Canada.
[Mitchell, S.; de Cabo, R.] NIA, Baltimore, MD 21224 USA.
[Le Couteur, D.] Concord Hosp, Concord, NSW, Australia.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0016-9013
EI 1758-5341
J9 GERONTOLOGIST
JI Gerontologist
PD NOV
PY 2016
VL 56
SU 3
BP 348
EP 349
PG 2
WC Gerontology
SC Geriatrics & Gerontology
GA ED1DT
UT WOS:000388585001572
ER
PT J
AU Sardina, A
Gamaldo, A
Andel, R
Evans, M
Zonderman, AB
AF Sardina, A.
Gamaldo, A.
Andel, R.
Evans, M.
Zonderman, A. B.
TI PAIN AND PHYSICAL FUNCTION IN A RACIALLY AND SOCIOECONOMICALLY DIVERSE
SAMPLE OF MIDDLE-AGED ADULTS
SO GERONTOLOGIST
LA English
DT Meeting Abstract
C1 [Sardina, A.; Gamaldo, A.; Andel, R.] Univ S Florida, Tampa, FL USA.
[Gamaldo, A.; Evans, M.; Zonderman, A. B.] NIA, Baltimore, MD 21224 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0016-9013
EI 1758-5341
J9 GERONTOLOGIST
JI Gerontologist
PD NOV
PY 2016
VL 56
SU 3
BP 418
EP 418
PG 1
WC Gerontology
SC Geriatrics & Gerontology
GA ED1DT
UT WOS:000388585002012
ER
PT J
AU Shardell, M
Bandinelli, S
Colpo, M
Ferrucci, L
AF Shardell, M.
Bandinelli, S.
Colpo, M.
Ferrucci, L.
TI LONGITUDINAL 25-HYDROXYVITAMIN D AND DEPRESSIVE SYMPTOMS WITH STRUCTURAL
MODELS: THE INCHIANTI STUDY
SO GERONTOLOGIST
LA English
DT Meeting Abstract
C1 [Shardell, M.; Ferrucci, L.] NIA, Translat Gerontol Branch, Baltimore, MD 21224 USA.
[Bandinelli, S.; Colpo, M.] LHTC, Local Hlth Unit, Tuscany Ctr, Geriatr Unit, Florence, Italy.
[Colpo, M.] Univ Firenze, Dept Stat Informat & Applicat, Florence, Italy.
NR 0
TC 0
Z9 0
U1 2
U2 2
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0016-9013
EI 1758-5341
J9 GERONTOLOGIST
JI Gerontologist
PD NOV
PY 2016
VL 56
SU 3
BP 438
EP 438
PG 1
WC Gerontology
SC Geriatrics & Gerontology
GA ED1DT
UT WOS:000388585002084
ER
PT J
AU Wilkinson, M
Luo, S
Gabriel, KP
Tanaka, T
Simonsick, E
Day, R
AF Wilkinson, M.
Luo, S.
Gabriel, K. Pettee
Tanaka, T.
Simonsick, E.
Day, R.
TI A HOMOCYSTEINE METABOLISM BASED DIET PATTERN AND PHYSICAL FUNCTION IN
OLDER ADULTS
SO GERONTOLOGIST
LA English
DT Meeting Abstract
C1 [Wilkinson, M.; Luo, S.; Day, R.] UTHlth Sch Publ Hlth Houston, Houston, TX USA.
[Tanaka, T.; Simonsick, E.] NIA, Baltimore, MD 21224 USA.
[Gabriel, K. Pettee] UTHlth Sch Publ Hlth Austin, Austin Reg Campus, Austin, TX USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0016-9013
EI 1758-5341
J9 GERONTOLOGIST
JI Gerontologist
PD NOV
PY 2016
VL 56
SU 3
BP 455
EP 455
PG 1
WC Gerontology
SC Geriatrics & Gerontology
GA ED1DT
UT WOS:000388585002152
ER
PT J
AU Schrack, J
Leroux, A
Fleg, J
Simonsick, E
Zipunnikov, V
Studenski, S
Ferrucci, L
Crainiceanu, C
AF Schrack, J.
Leroux, A.
Fleg, J.
Simonsick, E.
Zipunnikov, V.
Studenski, S.
Ferrucci, L.
Crainiceanu, C.
TI GETTING TO THE HEART OF THE MATTER: USING HEART RATE TO DEFINE PHYSICAL
ACTIVITY INTENSITY
SO GERONTOLOGIST
LA English
DT Meeting Abstract
C1 [Schrack, J.; Leroux, A.; Zipunnikov, V.; Crainiceanu, C.] Johns Hopkins Bloomberg Sch Publ Hlth, Epidemiol, Baltimore, MD USA.
[Fleg, J.] NHLBI, Bldg 10, Bethesda, MD 20892 USA.
[Simonsick, E.; Studenski, S.; Ferrucci, L.] NIA, Baltimore, MD 21224 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0016-9013
EI 1758-5341
J9 GERONTOLOGIST
JI Gerontologist
PD NOV
PY 2016
VL 56
SU 3
BP 469
EP 470
PG 2
WC Gerontology
SC Geriatrics & Gerontology
GA ED1DT
UT WOS:000388585002209
ER
PT J
AU Ashida, S
Marcum, CS
Koehly, L
AF Ashida, S.
Marcum, C. S.
Koehly, L.
TI SOCIAL INTERACTION CHARACTERISTICS ASSOCIATED WITH PERCEPTIONS OF UNMET
EXPECTATIONS IN CAREGIVING
SO GERONTOLOGIST
LA English
DT Meeting Abstract
C1 [Ashida, S.] Univ Iowa, Coll Publ Hlth, Community & Behav Hlth, Iowa City, IA USA.
[Marcum, C. S.; Koehly, L.] NHGRI, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0016-9013
EI 1758-5341
J9 GERONTOLOGIST
JI Gerontologist
PD NOV
PY 2016
VL 56
SU 3
BP 493
EP 494
PG 2
WC Gerontology
SC Geriatrics & Gerontology
GA ED1DT
UT WOS:000388585002309
ER
PT J
AU Das, S
Roberts, S
Ravussin, E
Holloszy, J
Hadley, E
Romashkan, S
Kraus, W
AF Das, S.
Roberts, S.
Ravussin, E.
Holloszy, J.
Hadley, E.
Romashkan, S.
Kraus, W.
TI FINDINGS FROM A TWO-YEAR RANDOMIZED CONTROLLED TRIAL OF HUMAN CALORIC
RESTRICTION
SO GERONTOLOGIST
LA English
DT Meeting Abstract
C1 [Das, S.; Roberts, S.] Tufts Univ, Energy Metab, Jean Mayer USDA, HNRCA, Boston, MA 02111 USA.
[Ravussin, E.] PBRC, Baton Rouge, LA USA.
[Holloszy, J.] Washington Univ, St Louis, MO USA.
[Hadley, E.; Romashkan, S.] NIA, NIH, Bethesda, MD 20892 USA.
[Kraus, W.] Duke Univ, Durham, NC USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0016-9013
EI 1758-5341
J9 GERONTOLOGIST
JI Gerontologist
PD NOV
PY 2016
VL 56
SU 3
BP 497
EP 497
PG 1
WC Gerontology
SC Geriatrics & Gerontology
GA ED1DT
UT WOS:000388585002324
ER
PT J
AU Sheets, DJ
Beach, C
Hundza, S
Mitz, A
MacDonald, S
Asche, C
Gali, B
AF Sheets, D. J.
Beach, C.
Hundza, S.
Mitz, A.
MacDonald, S.
Asche, C.
Gali, B.
TI CAREGIVER PERCEPTIONS OF TECHNOLOGIES TO SUPPORT COMMUNITY-DWELLING
OLDER ADULTS WITH DEMENTIA
SO GERONTOLOGIST
LA English
DT Meeting Abstract
C1 [Sheets, D. J.; Hundza, S.; MacDonald, S.; Asche, C.; Gali, B.] Univ Victoria, Sch Nursing, Victoria, BC, Canada.
[Beach, C.] Canadian Inst Hlth Informat, Victoria, BC, Canada.
[Mitz, A.] NIMH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 2
U2 2
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0016-9013
EI 1758-5341
J9 GERONTOLOGIST
JI Gerontologist
PD NOV
PY 2016
VL 56
SU 3
BP 526
EP 526
PG 1
WC Gerontology
SC Geriatrics & Gerontology
GA ED1DT
UT WOS:000388585002446
ER
PT J
AU Quinones, A
Markwardt, S
Rostant, OS
Vasquez, E
Thielke, S
Botoseneanu, A
AF Quinones, A.
Markwardt, S.
Rostant, O. S.
Vasquez, E.
Thielke, S.
Botoseneanu, A.
TI MULTIMORBIDITY COMBINATION ASSOCIATIONS WITH PROSPECTIVE DISABILITY IN
THE NHATS
SO GERONTOLOGIST
LA English
DT Meeting Abstract
C1 [Quinones, A.; Markwardt, S.] Oregon Hlth & Sci Univ, Sch Publ Hlth, Portland, OR 97201 USA.
[Rostant, O. S.] NIA, Intramural Res Program, Bethesda, MD 20892 USA.
[Vasquez, E.] SUNY Albany, Albany, NY 12222 USA.
[Thielke, S.] Puget Sound VA Med Ctr, Seattle, WA USA.
[Thielke, S.] Univ Washington, Seattle, WA 98195 USA.
[Botoseneanu, A.] Univ Michigan, Dearborn, MI 48128 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0016-9013
EI 1758-5341
J9 GERONTOLOGIST
JI Gerontologist
PD NOV
PY 2016
VL 56
SU 3
BP 529
EP 529
PG 1
WC Gerontology
SC Geriatrics & Gerontology
GA ED1DT
UT WOS:000388585002457
ER
PT J
AU Armstrong, N
Gross, A
Andrews, R
Varma, V
Xue, Q
Carlson, M
AF Armstrong, N.
Gross, A.
Andrews, R.
Varma, V.
Xue, Q.
Carlson, M.
TI ASSOCIATION BETWEEN TRIAL-LEVEL CHANGE IN STROOP TEST AND MOBILITY:
BALTIMORE EXPERIENCE CORPS TRIAL
SO GERONTOLOGIST
LA English
DT Meeting Abstract
C1 [Armstrong, N.; Gross, A.; Andrews, R.; Xue, Q.; Carlson, M.] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA.
[Varma, V.] NIA, Baltimore, MD 21224 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0016-9013
EI 1758-5341
J9 GERONTOLOGIST
JI Gerontologist
PD NOV
PY 2016
VL 56
SU 3
BP 541
EP 541
PG 1
WC Gerontology
SC Geriatrics & Gerontology
GA ED1DT
UT WOS:000388585002496
ER
PT J
AU Tian, Q
Resnick, SM
Landman, BA
Ferrucci, L
Studenski, S
AF Tian, Q.
Resnick, S. M.
Landman, B. A.
Ferrucci, L.
Studenski, S.
TI AGE-RELATED WHITE MATTER MICROSTRUCTURAL CHANGES AND GAIT DECLINE
SO GERONTOLOGIST
LA English
DT Meeting Abstract
C1 [Tian, Q.; Resnick, S. M.; Ferrucci, L.; Studenski, S.] NIA, Translat Gerontol Branch, Baltimore, MD 21224 USA.
[Landman, B. A.] Vanderbilt Univ, 221 Kirkland Hall, Nashville, TN 37235 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0016-9013
EI 1758-5341
J9 GERONTOLOGIST
JI Gerontologist
PD NOV
PY 2016
VL 56
SU 3
BP 560
EP 560
PG 1
WC Gerontology
SC Geriatrics & Gerontology
GA ED1DT
UT WOS:000388585002561
ER
PT J
AU Marcum, CS
Koehly, L
AF Marcum, C. S.
Koehly, L.
TI THE EFFECT OF AGE AND MULTIPLEXITY ON HEALTH DISCUSSION NETWORKS
SO GERONTOLOGIST
LA English
DT Meeting Abstract
C1 [Marcum, C. S.; Koehly, L.] NIH, Bldg 10, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0016-9013
EI 1758-5341
J9 GERONTOLOGIST
JI Gerontologist
PD NOV
PY 2016
VL 56
SU 3
BP 590
EP 590
PG 1
WC Gerontology
SC Geriatrics & Gerontology
GA ED1DT
UT WOS:000388585002677
ER
PT J
AU Onken, L
AF Onken, L.
TI NEW FEDERAL MODELS AND FUNDING INITIATIVES TO ENCOURAGE TRANSLATIONAL
AND IMPLEMENTATION RESEARCH
SO GERONTOLOGIST
LA English
DT Meeting Abstract
C1 [Onken, L.] NIA, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0016-9013
EI 1758-5341
J9 GERONTOLOGIST
JI Gerontologist
PD NOV
PY 2016
VL 56
SU 3
BP 608
EP 609
PG 2
WC Gerontology
SC Geriatrics & Gerontology
GA ED1DT
UT WOS:000388585002754
ER
PT J
AU Mair, C
Zweiacher, H
Waldstein, S
Lehning, A
Evans, M
Zonderman, AB
AF Mair, C.
Zweiacher, H.
Waldstein, S.
Lehning, A.
Evans, M.
Zonderman, A. B.
TI SOCIAL ENVIRONMENT AND SOCIAL SUPPORT IN BALTIMORE CITY: AN EXPLORATION
OF NEIGHBORHOOD CONTEXTS
SO GERONTOLOGIST
LA English
DT Meeting Abstract
C1 [Mair, C.; Zweiacher, H.; Waldstein, S.] Univ Maryland Baltimore Cty, Baltimore, MD 21228 USA.
[Evans, M.; Zonderman, A. B.] NIA, Baltimore, MD 21224 USA.
[Lehning, A.] Univ Maryland, Baltimore, MD 21201 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0016-9013
EI 1758-5341
J9 GERONTOLOGIST
JI Gerontologist
PD NOV
PY 2016
VL 56
SU 3
BP 714
EP 714
PG 1
WC Gerontology
SC Geriatrics & Gerontology
GA ED1DT
UT WOS:000388585003372
ER
PT J
AU Wright, RS
Waldstein, S
Gerassimakis, C
Sprung, M
Moody, DLB
Taylor, A
Evans, MK
Zonderman, AB
AF Wright, R. S.
Waldstein, S.
Gerassimakis, C.
Sprung, M.
Moody, D. L. Beatty
Taylor, A.
Evans, M. K.
Zonderman, A. B.
TI PREDICTORS OF NEUROCOGNITIVE PERFORMANCE AMONG AFRICAN AMERICANS
ENROLLED IN THE HANDLS STUDY
SO GERONTOLOGIST
LA English
DT Meeting Abstract
C1 [Wright, R. S.; Gerassimakis, C.] Univ Delaware, Sch Nursing, Newark, DE USA.
[Waldstein, S.; Moody, D. L. Beatty; Taylor, A.] Univ Maryland Baltimore Cty, Baltimore, MD 21228 USA.
[Sprung, M.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA.
[Evans, M. K.; Zonderman, A. B.] NIA, Baltimore, MD 21224 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0016-9013
EI 1758-5341
J9 GERONTOLOGIST
JI Gerontologist
PD NOV
PY 2016
VL 56
SU 3
BP 733
EP 734
PG 2
WC Gerontology
SC Geriatrics & Gerontology
GA ED1DT
UT WOS:000388585003446
ER
PT J
AU Moody, DLB
Waldstein, S
Al-Najjar, E
Evans, MK
Zonderman, AB
AF Moody, D. L. Beatty
Waldstein, S.
Al-Najjar, E.
Evans, M. K.
Zonderman, A. B.
TI SOCIAL PATTERNING OF MULTIPLE FORMS OF DISCRIMINATION IN AFRICAN
AMERICAN ADULTS IN THE HANDLS STUDY
SO GERONTOLOGIST
LA English
DT Meeting Abstract
C1 [Moody, D. L. Beatty; Waldstein, S.; Al-Najjar, E.] Univ Maryland Baltimore Cty, Dept Psychol, Baltimore, MD 21228 USA.
[Evans, M. K.; Zonderman, A. B.] NIA, Baltimore, MD 21224 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0016-9013
EI 1758-5341
J9 GERONTOLOGIST
JI Gerontologist
PD NOV
PY 2016
VL 56
SU 3
BP 734
EP 734
PG 1
WC Gerontology
SC Geriatrics & Gerontology
GA ED1DT
UT WOS:000388585003448
ER
PT J
AU Lines, L
Cohen, J
Halpern, MT
Lines, L
Kent, E
Smith, AW
Halpern, MT
AF Lines, L.
Cohen, J.
Halpern, M. T.
Lines, L.
Kent, E.
Smith, A. Wilder
Halpern, M. T.
TI Experiences of Care Among Dually Eligible Beneficiaries With and Without
Cancer: SEER-CAHPS, 2007-2013
SO GERONTOLOGIST
LA English
DT Meeting Abstract
C1 [Lines, L.; Cohen, J.; Halpern, M. T.] RTI Int, Qual Measurement & Hlth Policy, Waltham, MA USA.
[Lines, L.] Univ Massachusetts, Sch Med, Worcester, MA USA.
[Kent, E.; Smith, A. Wilder] NCI, Rockville, MD USA.
[Halpern, M. T.] Temple Univ, Philadelphia, PA 19122 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0016-9013
EI 1758-5341
J9 GERONTOLOGIST
JI Gerontologist
PD NOV
PY 2016
VL 56
SU 3
PG 1
WC Gerontology
SC Geriatrics & Gerontology
GA ED1DT
UT WOS:000388585003606
ER
PT J
AU Wahl, D
Cogger, V
Solon-Biet, S
Le Couteur, D
de Cabo, R
Simpson, S
AF Wahl, D.
Cogger, V.
Solon-Biet, S.
Le Couteur, D.
de Cabo, R.
Simpson, S.
TI Is a Low-Protein, High-Carbohydrate Diet an Essential Key to Brain
Health?
SO GERONTOLOGIST
LA English
DT Meeting Abstract
C1 [Wahl, D.; Cogger, V.; Solon-Biet, S.; Le Couteur, D.] Charles Perkins Ctr, ANZAC Res Inst, Pyrmont, NSW, Australia.
[de Cabo, R.] NIA, NIH, Baltimore, MD 21224 USA.
[Simpson, S.] Charles Perkins Ctr, Sydney, NSW, Australia.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0016-9013
EI 1758-5341
J9 GERONTOLOGIST
JI Gerontologist
PD NOV
PY 2016
VL 56
SU 3
PG 1
WC Gerontology
SC Geriatrics & Gerontology
GA ED1DT
UT WOS:000388585003571
ER
PT J
AU Le Gall, C
Laurent, J
Vince, N
Lizee, A
Agrawal, A
Walencik, A
Rettman, P
Gagne, K
Retiere, C
Hollenbach, J
Cesbron, A
Limou, S
Gourraud, PA
AF Le Gall, Caroline
Laurent, Julie
Vince, Nicolas
Lizee, Antoine
Agrawal, Alisha
Walencik, Alexandre
Rettman, Pauline
Gagne, Katia
Retiere, Christelle
Hollenbach, Jill
Cesbron, Anne
Limou, Sophie
Gourraud, Pierre-Antoine
TI Multidimensional reduction of multicentric cohort heterogeneity: An
alternative method to increase statistical power and robustness
SO HUMAN IMMUNOLOGY
LA English
DT Article
DE Multidimensional reduction; Multiple correspondence analyses;
Multicentric cohort; Heterogeneity; Hematopoietic stem cell
transplantation
ID CLINICAL-TRIALS; TRANSPLANTATION; DESIGN; MODELS
AB Modern clinical research takes advantage of multicentric cohorts to increase sample size and gain in statistical power. However, combining individuals from different recruitment centers provides heterogeneity in the dataset that needs to be accounted for to obtain robust results. Sophisticated statistical multivariate models adjusting for center effect can be implemented, but they can become unstable and can be complex to interpret with the increasing number of covariates to consider. Here, we present a multidimensional reduction technique to identify heterogeneity in a French multicentric cohort of hematopoietic stem cell transplantations and characterize a homogeneous subgroup prior to performing simple statistical univariate analyses. The exclusion of outliers allowed the identification of two genetic factors associated with post-transplantation overall survival. We therefore provide proof-of-concept that a sample size reduction method can efficiently account for heterogeneity and center effect in multicentric cohorts while increasing statistical power and robustness for discovery of new association signals. (C) 2016 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.
C1 [Le Gall, Caroline; Laurent, Julie; Gourraud, Pierre-Antoine] Methodomics, Toulouse, France.
[Vince, Nicolas] Leidos Biomed Res Inc, Frederick Natl Lab, Canc & Inflammat Program, Expt Immunol Lab, Frederick, MD USA.
[Vince, Nicolas] Ragon Inst MGH MIT & Harvard, Cambridge, MA USA.
[Lizee, Antoine; Agrawal, Alisha; Hollenbach, Jill; Gourraud, Pierre-Antoine] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA.
[Walencik, Alexandre; Rettman, Pauline; Gagne, Katia; Retiere, Christelle; Cesbron, Anne; Gourraud, Pierre-Antoine] Etab Francais Sang, Nantes, France.
[Walencik, Alexandre] Hosp Nantes, Inserm Unit 1064, Nantes, France.
[Walencik, Alexandre] Univ Nantes, Inserm Unit 1064, Nantes, France.
[Limou, Sophie] NCI, Mol Genet Epidemiol Sect, Basic Res Lab, Basic Sci Program,NIH,Leidos Biomed Res Inc,Frede, Frederick, MD 21701 USA.
RP Gourraud, PA (reprint author), CHU Nantes, ATIP Avenir Team Translat Immunogen Transplantat, CRTI, UMR Inserm 1064, 30 Bd Jean Monnet 1er Etage, F-44093 Nantes 1, France.
EM pierre-antoine.gourraud@univ-nantes.fr
OI Lizee, Antoine/0000-0002-1073-3190
NR 16
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 0198-8859
EI 1879-1166
J9 HUM IMMUNOL
JI Hum. Immunol.
PD NOV
PY 2016
VL 77
IS 11
SI SI
BP 1024
EP 1029
DI 10.1016/j.humimm.2016.05.013
PG 6
WC Immunology
SC Immunology
GA EE4II
UT WOS:000389565100004
PM 27262455
ER
PT J
AU Ding, XR
Zhao, N
Yang, GZ
Pettigrew, RI
Lo, B
Miao, F
Li, Y
Liu, J
Zhang, YT
AF Ding, Xiao-Rong
Zhao, Ni
Yang, Guang-Zhong
Pettigrew, Roderic I.
Lo, Benny
Miao, Fen
Li, Ye
Liu, Jing
Zhang, Yuan-Ting
TI Continuous Blood Pressure Measurement From Invasive to Unobtrusive:
Celebration of 200th Birth Anniversary of Carl Ludwig
SO IEEE JOURNAL OF BIOMEDICAL AND HEALTH INFORMATICS
LA English
DT Article
DE Carl ludwig; continuous; cuffless blood pressure (BP); kymograph;
unobtrusive
ID PULSE TRANSIT-TIME; CUFF-LESS; TRACKING CAPABILITIES;
CLINICAL-EVALUATION; HEALTH INFORMATICS; ARRIVAL-TIME; SENSOR; WAVE;
ACCURACY; DEVICE
AB The year 2016 marks the 200th birth anniversary of Carl Friedrich Wilhelm Ludwig (1816-1895). As one of the most remarkable scientists, Ludwig invented the kymograph, which for the first time enabled the recording of continuous blood pressure (BP), opening the door to the modern study of physiology. Almost a century later, intra-arterial BP monitoring through an arterial line has been used clinically. Subsequently, arterial tonometry and volume clamp method were developed and applied in continuous BP measurement in a noninvasive way. In the last two decades, additional efforts have been made to transform the method of unobtrusive continuous BP monitoring without the use of a cuff. This review summarizes the key milestones in continuous BP measurement; that is, kymograph, intra-arterial BP monitoring, arterial tonometry, volume clamp method, and cuffless BP technologies. Our emphasis is on recent studies of unobtrusive BP measurements as well as on challenges and future directions.
C1 [Ding, Xiao-Rong; Zhao, Ni; Liu, Jing; Zhang, Yuan-Ting] Chinese Univ Hong Kong, Dept Elect Engn, Hong Kong, Hong Kong, Peoples R China.
[Yang, Guang-Zhong; Lo, Benny] Imperial Coll London, Hamlyn Ctr, London SW7 2AZ, England.
[Pettigrew, Roderic I.] Natl Inst Biomed Imaging & Bioengn, NIH, Bethesda, MD 20892 USA.
[Miao, Fen; Li, Ye] Chinese Acad Sci, Shenzhen Inst Adv Technol, Dept Biomed & Hlth Engn, Shenzhen 518055, Peoples R China.
[Miao, Fen; Li, Ye; Zhang, Yuan-Ting] Chinese Acad Sci, Shenzhen Inst Adv Technol, Key Lab Hlth Informat, Shenzhen 518055, Peoples R China.
RP Zhang, YT (reprint author), Chinese Univ Hong Kong, Dept Elect Engn, Hong Kong, Hong Kong, Peoples R China.; Zhang, YT (reprint author), Chinese Acad Sci, Shenzhen Inst Adv Technol, Key Lab Hlth Informat, Shenzhen 518055, Peoples R China.
EM xrding@ee.cuhk.edu.hk; nzhao@ee.cuhk.edu.hk; g.z.yang@imperial.ac.uk;
rpettig@mail.nih.gov; benny.lo@imperial.ac.uk; fen.miao@siat.ac.cn;
ye.li@siat.ac.cn; jingliu@ee.cuhk.edu.hk; ytzhang@ee.cuhk.edu.hk
FU Innovation and Technology Fund from the Innovation and Technology
Commission of Hong Kong [ITS/275/15FP]
FX The work was supported in part by the Innovation and Technology Fund
(Ref. ITS/275/15FP) from the Innovation and Technology Commission of
Hong Kong.
NR 112
TC 0
Z9 0
U1 8
U2 8
PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC
PI PISCATAWAY
PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA
SN 2168-2194
J9 IEEE J BIOMED HEALTH
JI IEEE J. Biomed. Health Inform.
PD NOV
PY 2016
VL 20
IS 6
BP 1455
EP 1465
DI 10.1109/JBHI.2016.2620995
PG 11
WC Computer Science, Information Systems; Computer Science,
Interdisciplinary Applications; Mathematical & Computational Biology;
Medical Informatics
SC Computer Science; Mathematical & Computational Biology; Medical
Informatics
GA EE8AN
UT WOS:000389846700001
PM 28113184
ER
PT J
AU Guo, P
Banerjee, K
Stanley, RJ
Long, R
Antani, S
Thoma, G
Zuna, R
Frazier, SR
Moss, RH
Stoecker, WV
AF Guo, Peng
Banerjee, Koyel
Stanley, R. Joe
Long, Rodney
Antani, Sameer
Thoma, George
Zuna, Rosemary
Frazier, Shelliane R.
Moss, Randy H.
Stoecker, William V.
TI Nuclei-Based Features for Uterine Cervical Cancer Histology Image
Analysis With Fusion-Based Classification
SO IEEE JOURNAL OF BIOMEDICAL AND HEALTH INFORMATICS
LA English
DT Article
DE Cervical cancer; cervical intraepithelial neoplasia (CIN); fusion-based
classification; image processing; linear discriminant analysis (LDA);
support vector machine (SVM)
ID INTRAEPITHELIAL NEOPLASIA CIN; SELECTION
AB Cervical cancer, which has been affecting women worldwide as the second most common cancer, can be cured if detected early and treated well. Routinely, expert pathologists visually examine histology slides for cervix tissue abnormality assessment. In previous research, we investigated an automated, localized, fusion-based approach for classifying squamous epithelium into Normal, CIN1, CIN2, and CIN3 grades of cervical intraepithelial neoplasia (CIN) based on image analysis of 61 digitized histology images. This paper introduces novel acellular and atypical cell concentration features computed from vertical segment partitions of the epithelium region within digitized histology images to quantize the relative increase in nuclei numbers as the CIN grade increases. Based on the CIN grade assessments from two expert pathologists, image-based epithelium classification is investigated with voting fusion of vertical segments using support vector machine and linear discriminant analysis approaches. Leaveone-out is used for the training and testing for CIN classification, achieving an exact grade labeling accuracy as high as 88.5%.
C1 [Guo, Peng; Banerjee, Koyel; Stanley, R. Joe; Moss, Randy H.] Missouri Univ Sci & Technol, Dept Elect & Comp Engn, Rolla, MO 65409 USA.
[Long, Rodney; Antani, Sameer; Thoma, George] NIH, Lister Hill Natl Ctr Biomed Commun, Natl Lib Med, DHHS, Bethesda, MD 20894 USA.
[Zuna, Rosemary] Univ Oklahoma, Hlth Sci Ctr, Dept Pathol, Oklahoma City, OK 73117 USA.
[Frazier, Shelliane R.] Univ Missouri, Dept Surg Pathol, Hosp & Clin, Columbia, MO 65202 USA.
[Stoecker, William V.] Stoecker & Associates, Rolla, MO 65401 USA.
RP Guo, P (reprint author), Missouri Univ Sci & Technol, Dept Elect & Comp Engn, Rolla, MO 65409 USA.
EM kbnm6@mst.edu; stanleyj@mst.edu; long@nlm.nih.gov; antani@nlm.nih.gov;
gthoma@mail.nih.gov; rosemary-zuna@ouhsc.edu;
FrazierSR@health.missouri.edu; rhm@mst.edu; wvs@mst.edu
FU Intramural Research Program of the National Institutes of Health;
National Library of Medicine; Lister Hill National Center for Biomedical
Communications
FX This work was supported in part by the Intramural Research Program of
the National Institutes of Health, the National Library of Medicine, and
the Lister Hill National Center for Biomedical Communications.
NR 28
TC 0
Z9 0
U1 1
U2 1
PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC
PI PISCATAWAY
PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA
SN 2168-2194
J9 IEEE J BIOMED HEALTH
JI IEEE J. Biomed. Health Inform.
PD NOV
PY 2016
VL 20
IS 6
BP 1595
EP 1607
DI 10.1109/JBHI.2015.2483318
PG 13
WC Computer Science, Information Systems; Computer Science,
Interdisciplinary Applications; Mathematical & Computational Biology;
Medical Informatics
SC Computer Science; Mathematical & Computational Biology; Medical
Informatics
GA EE8AN
UT WOS:000389846700015
PM 26529792
ER
PT J
AU Bacon, SL
Czajkowski, SM
Lavoie, KL
Freedland, KE
AF Bacon, S. L.
Czajkowski, S. M.
Lavoie, K. L.
Freedland, K. E.
TI THE INTERNATIONAL BEHAVIOURAL TRIALS NETWORK (IBTN): AN INTERNATIONAL
EFFORT TO IMPROVE THE RIGOR AND IMPACT OF BEHAVIORAL CLINICAL TRIALS
SO INTERNATIONAL JOURNAL OF BEHAVIORAL MEDICINE
LA English
DT Meeting Abstract
C1 [Bacon, S. L.; Lavoie, K. L.] Hop Sacre Coeur Montreal, Montreal Behav Med Ctr, Montreal, PQ, Canada.
[Bacon, S. L.] Concordia Univ, Dept Exercise Sci, Montreal, PQ, Canada.
[Czajkowski, S. M.] NCI, Behav Res Program, Div Canc Control & Populat Sci, NIH, Betheseda, MD USA.
[Lavoie, K. L.] Univ Quebec Montreal, Dept Psychol, Montreal, PQ, Canada.
[Freedland, K. E.] Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA.
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 NOV
PY 2016
VL 23
SU 1
MA S163
BP S53
EP S54
PG 2
WC Psychology, Clinical
SC Psychology
GA ED6CV
UT WOS:000388943400174
ER
PT J
AU Czajkowski, SM
Naar, S
Powell, LH
Bacon, SL
AF Czajkowski, S. M.
Naar, S.
Powell, L. H.
Bacon, S. L.
TI NEW APPROACHES TO OBESITY PREVENTION AND TREATMENT: FINDINGS FROM THE
OBESITY-RELATED BEHAVIORAL INTERVENTION TRIALS (ORBIT) CONSORTIUM
SO INTERNATIONAL JOURNAL OF BEHAVIORAL MEDICINE
LA English
DT Meeting Abstract
C1 [Czajkowski, S. M.] NCI, Behav Res Program, Div Canc Control & Populat Sci, NIH, Bethesda, MD 20892 USA.
[Naar, S.] Wayne State Univ, Dept Family Med & Publ Hlth Sci, Detroit, MI USA.
[Powell, L. H.] Rush Univ, Med Ctr, Dept Prevent Med, Chicago, IL 60612 USA.
[Bacon, S. L.] Hop Sacre Coeur Montreal, Montreal Behav Med Ctr, Montreal, PQ, Canada.
[Bacon, S. L.] Concordia Univ, Dept Exercise Sci, Montreal, PQ, Canada.
EM Simon.bacon@concordia.ca
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 NOV
PY 2016
VL 23
SU 1
MA S380
BP S124
EP S124
PG 1
WC Psychology, Clinical
SC Psychology
GA ED6CV
UT WOS:000388943400393
ER
PT J
AU Czajkowski, SM
AF Czajkowski, S. M.
CA Obesity-Related Behavioral
TI THE OBESITY-RELATED BEHAVIORAL INTERVENTION TRIALS (ORBIT) CONSORTIUM:
DEVELOPING NEW WAYS TO PREVENT AND TREAT OBESITY
SO INTERNATIONAL JOURNAL OF BEHAVIORAL MEDICINE
LA English
DT Meeting Abstract
C1 [Czajkowski, S. M.; Obesity-Related Behavioral] NCI, Behav Res Program, Div Canc Control & Populat Sci, NIH, Bethesda, MD 20892 USA.
EM Susan.Czajkowski@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 NOV
PY 2016
VL 23
SU 1
MA S382
BP S124
EP S124
PG 1
WC Psychology, Clinical
SC Psychology
GA ED6CV
UT WOS:000388943400394
ER
PT J
AU Czajkowski, SM
Powell, LH
Naar, S
AF Czajkowski, S. M.
Powell, L. H.
Naar, S.
CA Obesity-Related Behav Intervention
TI DESIGNING MORE EFFECTIVE BEHAVIORAL TREATMENTS FOR CHRONIC DISEASES: THE
ORBIT MODEL FOR BEHAVIORAL INTERVENTION DEVELOPMENT
SO INTERNATIONAL JOURNAL OF BEHAVIORAL MEDICINE
LA English
DT Meeting Abstract
C1 [Czajkowski, S. M.] NCI, Behav Res Program, Div Canc Control & Populat Sci, NIH, Betheseda, MD USA.
[Powell, L. H.] Rush Univ, Med Ctr, Dept Prevent Med, Chicago, IL 60612 USA.
[Naar, S.] Wayne State Univ, Dept Family Med & Publ Hlth Sci, Detroit, MI USA.
NR 0
TC 0
Z9 0
U1 4
U2 4
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 NOV
PY 2016
VL 23
SU 1
MA S165
BP S54
EP S54
PG 1
WC Psychology, Clinical
SC Psychology
GA ED6CV
UT WOS:000388943400176
ER
PT J
AU Green, P
Colditz, G
van der Leeden, M
Emery, J
Suls, J
AF Green, P.
Colditz, G.
van der Leeden, M.
Emery, J.
Suls, J.
TI CANCER IN THE CONTEXT OF COMORBIDITY AND MULTIMORBIDITY: PERSPECTIVES
FROM BEHAVIOURAL MEDICINE
SO INTERNATIONAL JOURNAL OF BEHAVIORAL MEDICINE
LA English
DT Meeting Abstract
C1 [Green, P.; Suls, J.] NCI, Bethesda, MD USA.
[Colditz, G.] Washington Univ, Sch Med, St Louis, MO USA.
[van der Leeden, M.] Vrije Univ Amsterdam, Med Ctr, Amsterdam, Netherlands.
[Emery, J.] Univ Melbourne, Melbourne, Vic, Australia.
EM paige.green@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 NOV
PY 2016
VL 23
SU 1
MA S097
BP S32
EP S33
PG 2
WC Psychology, Clinical
SC Psychology
GA ED6CV
UT WOS:000388943400108
ER
PT J
AU Kaufmann, PG
Freedland, KE
Powell, LH
AF Kaufmann, Peter G.
Freedland, Kenneth E.
Powell, Lynda H.
TI ADVANCED CONCEPTS IN HIGH QUALITY RANDOMISED CLINICAL TRIALS - PART 2
SO INTERNATIONAL JOURNAL OF BEHAVIORAL MEDICINE
LA English
DT Meeting Abstract
C1 [Kaufmann, Peter G.] NHLBI, Div Cardiovasc Sci, NIH, Bethesda, MD USA.
[Freedland, Kenneth E.] Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63130 USA.
[Powell, Lynda H.] Rush Univ, Med Ctr, Dept Prevent Med, Chicago, IL USA.
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 NOV
PY 2016
VL 23
SU 1
MA 9
BP S2
EP S2
PG 1
WC Psychology, Clinical
SC Psychology
GA ED6CV
UT WOS:000388943400010
ER
PT J
AU Kaufmann, PG
Freedland, KE
Powell, LH
AF Kaufmann, Peter G.
Freedland, Kenneth E.
Powell, Lynda H.
TI ADVANCED CONCEPTS IN HIGH QUALITY RANDOMIZED CLINICAL TRIALS - PART 1
SO INTERNATIONAL JOURNAL OF BEHAVIORAL MEDICINE
LA English
DT Meeting Abstract
C1 [Kaufmann, Peter G.] NHLBI, Div Cardiovasc Sci, NIH, Bethesda, MD USA.
[Freedland, Kenneth E.] Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63130 USA.
[Powell, Lynda H.] Rush Univ, Med Ctr, Dept Prevent Med, Chicago, IL USA.
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 NOV
PY 2016
VL 23
SU 1
MA 3
BP S1
EP S1
PG 1
WC Psychology, Clinical
SC Psychology
GA ED6CV
UT WOS:000388943400005
ER
PT J
AU McGregor, LM
Wilson, C
Myers, RE
Klein, W
Flight, I
von Wagner, C
AF McGregor, L. M.
Wilson, C.
Myers, R. E.
Klein, W.
Flight, I.
von Wagner, C.
TI COLORECTAL CANCER SCREENING: HOW TO ENGAGE INVITEES AND KEEP THEM COMING
BACK FOR MORE
SO INTERNATIONAL JOURNAL OF BEHAVIORAL MEDICINE
LA English
DT Meeting Abstract
C1 [McGregor, L. M.; von Wagner, C.] UCL, Dept Epidemiol & Publ Hlth, CR UK Hlth Behav Res Ctr, London, England.
[Wilson, C.; Flight, I.] Flinders Univ S Australia, Flinders Ctr Innovat Canc, Adelaide, SA, Australia.
[Wilson, C.; Flight, I.] Canc Council South Australia, Adelaide, SA, Australia.
[Myers, R. E.] Thomas Jefferson Univ, Dept Med Oncol, Div Populat Sci, Philadelphia, PA 19107 USA.
[Klein, W.] NCI, NIH, DHHS, 9609 Med Ctr Dr,Room 3E140,MSC 9761, Bethesda, MD 20892 USA.
EM kleinwm@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 NOV
PY 2016
VL 23
SU 1
MA S397
BP S129
EP S129
PG 1
WC Psychology, Clinical
SC Psychology
GA ED6CV
UT WOS:000388943400409
ER
PT J
AU Sheeran, P
Rothman, A
Abraham, C
Klein, W
AF Sheeran, Paschal
Rothman, Alexander
Abraham, Charles
Klein, William
TI UNDERSTANDING WHAT WORKS IN INTERVENTIONS DESIGNED TO CHANGE HEALTH
BEHAVIOUR: NEW APPROACHES TO LINKING THEORY RESEARCH DESIGN, AND
EVIDENCE
SO INTERNATIONAL JOURNAL OF BEHAVIORAL MEDICINE
LA English
DT Meeting Abstract
C1 [Sheeran, Paschal] Univ N Carolina, Chapel Hill, NC USA.
[Rothman, Alexander] Univ Minnesota, Minneapolis, MN 55455 USA.
[Abraham, Charles] Univ Exeter, Psychol Appl Hlth, Sch Med, Exeter, Devon, England.
[Klein, William] NCI, Bethesda, MD 20892 USA.
EM psheeran@email.unc.edu
NR 0
TC 0
Z9 0
U1 1
U2 1
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 NOV
PY 2016
VL 23
SU 1
MA S669
BP S216
EP S217
PG 2
WC Psychology, Clinical
SC Psychology
GA ED6CV
UT WOS:000388943400679
ER
PT J
AU Waller, J
Haddrell, J
Chorley, A
Ferrer, R
Marlow, L
AF Waller, J.
Haddrell, J.
Chorley, A.
Ferrer, R.
Marlow, L.
TI USING THE PRECAUTION ADOPTION PROCESS MODEL TO UNDERSTAND
NON-PARTICIPATION IN CERVICAL SCREENING
SO INTERNATIONAL JOURNAL OF BEHAVIORAL MEDICINE
LA English
DT Meeting Abstract
C1 [Waller, J.; Haddrell, J.; Chorley, A.; Marlow, L.] UCL, Dept Epidemiol & Publ Hlth, Hlth Behav Res Ctr, London, England.
[Ferrer, R.] NCI, Behav Res Programme, Div Canc Control & Populat Sci, Rockville, MD USA.
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 NOV
PY 2016
VL 23
SU 1
MA P548
BP S177
EP S177
PG 1
WC Psychology, Clinical
SC Psychology
GA ED6CV
UT WOS:000388943400558
ER
PT J
AU Houghton, LC
Ganmaa, D
Rosenberg, PS
Davaalkham, D
Stanczyk, FZ
Hoover, RN
Troisi, R
AF Houghton, Lauren C.
Ganmaa, Davaasambuu
Rosenberg, Philip S.
Davaalkham, Dambadarjaa
Stanczyk, Frank Z.
Hoover, Robert N.
Troisi, Rebecca
TI Associations of Breast Cancer Risk Factors with Premenopausal Sex
Hormones in Women with Very Low Breast Cancer Risk
SO INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH
LA English
DT Article
DE breast cancer; sex steroids; estrogen; progesterone; testosterone; urban
migration; Mongolia
ID LIFE-STYLE; BODY; ESTROGENS; AMERICAN; MONGOLIA; STEROIDS
AB Breast cancer incidence rates are low but rising in urban Mongolia. We collected reproductive and lifestyle factor information and measured anthropometrics and serum sex steroid concentrations among 314 premenopausal women living in Ulaanbaatar, Mongolia. Mean differences in hormone concentrations by these factors were calculated using age-adjusted quadratic regression splines. Estrone and estradiol in college-educated women were, respectively, 18.2% (p = 0.03) and 23.6% (p = 0.03) lower than in high-school-educated women. Progesterone concentrations appeared 55.8% lower (p = 0.10) in women residing in modern housing compared with women living in traditional housing (gers), although this finding was not statistically significant. Testosterone concentrations were positively associated with adiposity and central fat distribution; 17.1% difference (p = 0.001) for highest vs. lowest quarter for body mass index and 15.1% difference (p = 0.005) for waist-to-height ratio. Estrogens were higher in the follicular phase of women who breastfed each child for shorter durations. A distinct hormonal profile was associated with an urban lifestyle in premenopausal, Mongol women. In particular, heavier, more-educated women living in urban dwellings had higher testosterone and lower estrogen and progesterone levels. Higher breast cancer incidence in urban compared with rural women suggest that the hormonal profile associated with a more traditional lifestyle may be protective among Mongol women.
C1 [Houghton, Lauren C.] Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY 10032 USA.
[Ganmaa, Davaasambuu] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA.
[Ganmaa, Davaasambuu] Harvard TH Chan Sch Publ Hlth, Dept Nutr, Harvard Med Sch, Boston, MA 02115 USA.
[Rosenberg, Philip S.; Hoover, Robert N.; Troisi, Rebecca] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Davaalkham, Dambadarjaa] Hlth Sci Univ Mongolia, Ulaanbaatar 210648, Mongol Peo Rep.
[Stanczyk, Frank Z.] Univ Southern Calif, Keck Sch Med, Div Reprod Endocrinol & Infertil, Los Angeles, CA 90033 USA.
RP Troisi, R (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
EM lh2746@columbia.edu; gdavaasa@hsph.harvard.edu;
rosenbep@exchange.nih.gov; davaalham@yahoo.com; fstanczyk@att.net;
hooverr@mail.nih.gov; troisir@mail.nih.gov
FU Intramural Division of the National Cancer Institute at the National
Institutes of Health
FX This work was supported by the Intramural Division of the National
Cancer Institute at the National Institutes of Health.
NR 27
TC 0
Z9 0
U1 0
U2 0
PU MDPI AG
PI BASEL
PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND
SN 1660-4601
J9 INT J ENV RES PUB HE
JI Int. J. Environ. Res. Public Health
PD NOV
PY 2016
VL 13
IS 11
AR 1066
DI 10.3390/ijerph13111066
PG 12
WC Environmental Sciences; Public, Environmental & Occupational Health
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health
GA EE4KR
UT WOS:000389571300025
ER
PT J
AU Reznik, SE
Gardner, EL
Ashby, CR
AF Reznik, Sandra E.
Gardner, Eliot L.
Ashby, Charles R., Jr.
TI Cannabidiol: a potential treatment for post Ebola syndrome?
SO INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
DE Ebola virus; Cannabidiol; Post Ebola Syndrome; Phytocannabinoids
ID VIRUS DISEASE; SIERRA-LEONE; CANNABINOIDS; SURVIVORS; SEQUELAE
AB Patients recovered from Ebola virus infection may experience short-and long-term physical, neuropsychological and social sequelae, including arthralgia, musculoskeletal pain, ophthalmic inflammation, auditory problems, fatigue, confusion, insomnia, short-term memory impairment, anxiety, depression and anorexia, all lasting from two weeks to more than two years. Currently there are no treatments for post Ebola sequelae. We hypothesize that cannabidiol (CBD) may attenuate some of these post Ebola sequelae, several of which have been postulated to result from inflammation and/or an autoimmune response. CBD has anti-inflammatory actions in various animal models. Clinical studies have shown that oral administration of CBD, compared to placebo, significantly reduces anxiety, has antinociceptive and anticonvulsant actions, and may be therapeutic for insomnia. Overall, CBD has a number of pharmacological effects that may significantly improve the mental and somatic health of patients suffering from post Ebola sequelae. In humans, CBD, at therapeutic doses, does not: 1) elicit dependence or tolerance; 2) significantly alter heart rate or blood pressure; 3) affect gastrointestinal transit; 4) produce significant cognitive or psychomotor impairments. Mild sedation and nausea are the most commonly reported adverse effects associated with CBD. CBD, based on its pharmacological effects and favorable safety profile, should be considered as a treatment for individuals with post Ebola sequelae. (C) 2016 The Authors. Published by Elsevier Ltd on behalf of International Society for Infectious Diseases.
C1 [Reznik, Sandra E.; Ashby, Charles R., Jr.] St Johns Univ, Coll Pharm & Hlth Sci, Dept Pharmaceut Sci, Queens, NY USA.
[Reznik, Sandra E.] Montefiore Med Ctr, Albert Einstein Coll Med, Dept Pathol, 111 E 210th St, Bronx, NY 10467 USA.
[Reznik, Sandra E.] Montefiore Med Ctr, Albert Einstein Coll Med, Dept Obstet & Gynecol & Womens Hlth, 111 E 210th St, Bronx, NY 10467 USA.
[Gardner, Eliot L.] NIDA, NIH, Neuropsychopharmacol Sect, Mol Targets & Medicat Discovery Branch,Intramural, Bethesda, MD 20892 USA.
RP Ashby, CR (reprint author), St Johns Univ, Coll Pharm & Hlth Sci, Dept Pharmaceut Sci, Queens, NY USA.
EM cnsratdoc@optonline.net
NR 19
TC 0
Z9 0
U1 5
U2 5
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1201-9712
EI 1878-3511
J9 INT J INFECT DIS
JI Int. J. Infect. Dis.
PD NOV
PY 2016
VL 52
BP 74
EP 76
DI 10.1016/j.ijid.2016.09.020
PG 3
WC Infectious Diseases
SC Infectious Diseases
GA EE3RZ
UT WOS:000389516600015
PM 27686726
ER
PT J
AU Magnus, MC
Karlstad, O
Midtun, O
Haberg, SE
Tunheim, G
Parr, CL
Nafstad, P
London, SJ
Nilsen, RM
Ueland, PM
Nystad, W
AF Magnus, Maria C.
Karlstad, Oystein
Midtun, Oivind
Haberg, Siri E.
Tunheim, Gro
Parr, Christine L.
Nafstad, Per
London, Stephanie J.
Nilsen, Roy M.
Ueland, Per M.
Nystad, Wenche
TI Maternal plasma total neopterin and kynurenine/tryptophan levels during
pregnancy in relation to asthma development in the offspring
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Article
DE Asthma; kynurenine; neopterin; pregnancy; tryptophan
ID INDOLEAMINE 2,3-DIOXYGENASE; TRYPTOPHAN CATABOLISM; URINARY NEOPTERIN;
INTERFERON-GAMMA; NORWEGIAN MOTHER; VITAMIN STATUS; IMMUNE-SYSTEM; CHILD
COHORT; DISEASE; ACTIVATION
AB Background: Neopterin levels and kynurenine/tryptophan ratios (KTRs) increase with IFN-gamma stimulation, indicating T(H)1 immunity, and thus might be inversely associated with asthma.
Objective: We sought to examine the association of maternal neopterin levels and KTRs during pregnancy with asthma in the offspring.
Methods: We analyzed the associations of maternal plasma total neopterin levels and KTRs in midpregnancy with asthma at age 7 years among 2883 children in the Norwegian Mother and Child Cohort Study. Asthma was classified either based on registered dispensed asthma medications in the Norwegian Prescription Database or maternal report. We calculated adjusted relative risks using log-binomial regression.
Results: The median gestational week of blood sampling was 18 weeks (interquartile range, 17-19 weeks). The risk of dispensed asthma medications at age 7 years was highest among children of mothers in the highest quartile of neopterin levels, whereas the risk was similar in the 3 lowest quartiles. The adjusted relative risk of dispensed asthma medications was 1.66 (95% CI, 1.16-2.38) when comparing children of mothers in the highest quartile with those in the 3 lowest quartiles. A similar association was observed for maternal report of asthma at age 7 years. When we evaluated allergic versus nonallergic asthma, neopterin levels tended to be associated with nonallergic asthma. Maternal KTR was not associated with asthma development.
Conclusions: Our findings indicate that high maternal levels of neopterin, a marker of cellular immune activation, during pregnancy were positively associated with asthma in offspring. Experimental studies would be needed to further elucidate underlying mechanisms.
C1 [Magnus, Maria C.; Karlstad, Oystein; Haberg, Siri E.; Parr, Christine L.; Nafstad, Per; Nystad, Wenche] Norwegian Inst Publ Hlth, Div Mental & Phys Hlth, Oslo, Norway.
[Tunheim, Gro] Norwegian Inst Publ Hlth, Div Infect Control & Environm Hlth, Oslo, Norway.
[Midtun, Oivind] Bevital AS, Bergen, Norway.
[Nafstad, Per] Univ Oslo, Fac Med, Dept Community Med, Bergen, Norway.
[London, Stephanie J.] NIEHS, Epidemiol Branch, NIH, Res Triangle Pk, NC 27709 USA.
[Nilsen, Roy M.] Haukeland Hosp, Clin Res Ctr, Bergen, Norway.
[Ueland, Per M.] Haukeland Hosp, Lab Clin Biochem, Bergen, Norway.
[Ueland, Per M.] Univ Bergen, Dept Clin Sci, Bergen, Norway.
RP Magnus, MC (reprint author), Norwegian Inst Publ Hlth, Dept Chron Dis, POB 4404 Nydalen, Oslo, Norway.
EM Maria.Christine.Magnus@fhi.no
OI Karlstad, Oystein/0000-0003-1204-787X; London,
Stephanie/0000-0003-4911-5290
FU National Institute of Health (National Institute of Environmental Health
Sciences) [N01-ES-75558]; National Institute of Health (National
Institute of Neurological Disorders and Stroke) [UO1 NS 047537-01, UO1
NS 047537-06A1]; Norwegian Research Council/FUGE [151918/S10]; Norwegian
Research Council [221919]; Division of Intramural Research at the
National Institute of Environmental Health Sciences
FX Data collection in the Norwegian Mother and Child Cohort Study is
supported by National Institutes of Health (National Institute of
Environmental Health Sciences contract no. N01-ES-75558, National
Institute of Neurological Disorders and Stroke grants UO1 NS 047537-01
and UO1 NS 047537-06A1) and the Norwegian Research Council/FUGE (grant
no. 151918/S10). This work was supported by the Norwegian Research
Council (grant no. 221919 to W.N.). The work is also supported by the
Division of Intramural Research at the National Institute of
Environmental Health Sciences (to S.J.L.).
NR 35
TC 0
Z9 0
U1 1
U2 1
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0091-6749
EI 1097-6825
J9 J ALLERGY CLIN IMMUN
JI J. Allergy Clin. Immunol.
PD NOV
PY 2016
VL 138
IS 5
BP 1319
EP +
DI 10.1016/j.jaci.2016.02.032
PG 11
WC Allergy; Immunology
SC Allergy; Immunology
GA EE4AA
UT WOS:000389542700010
PM 27221136
ER
PT J
AU Jacobino, SR
Nederend, M
Hennus, M
Houben, ML
Ngwuta, JO
Viveen, M
Coenjaerts, FEJ
Hack, CE
van Neerven, RJJ
Graham, BS
Bont, L
Leusen, JHW
AF Jacobino, Shamir R.
Nederend, Maaike
Hennus, Marije
Houben, Michiel L.
Ngwuta, Joan O.
Viveen, Marco
Coenjaerts, Frank E. J.
Hack, C. Erik
van Neerven, R. J. Joost
Graham, Barney S.
Bont, Louis
Leusen, Jeanette H. W.
TI Human amniotic fluid antibodies protect the neonate against respiratory
syncytial virus infection
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Letter
ID RSV; IMMUNITY; CHILDREN; INFANTS
C1 [Jacobino, Shamir R.; Nederend, Maaike; Hennus, Marije; Hack, C. Erik; Bont, Louis; Leusen, Jeanette H. W.] UMC Utrecht, Lab Translat Immunol, Utrecht, Netherlands.
[Hennus, Marije; Bont, Louis] Wilhelmina Childrens Hosp, Dept Pediat, Utrecht, Netherlands.
[Ngwuta, Joan O.; Graham, Barney S.] NIAID, Viral Pathogenesis Lab, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Viveen, Marco; Coenjaerts, Frank E. J.] UMC Utrecht, Med Microbiol, Utrecht, Netherlands.
[van Neerven, R. J. Joost] Wageningen Univ, Cell Biol & Immunol, Wageningen, Netherlands.
RP Leusen, JHW (reprint author), UMC Utrecht, Lab Translat Immunol, Utrecht, Netherlands.
EM jleusen@umcutrecht.nl
OI Leusen, Jeanette/0000-0003-4982-6914
NR 9
TC 1
Z9 1
U1 0
U2 0
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0091-6749
EI 1097-6825
J9 J ALLERGY CLIN IMMUN
JI J. Allergy Clin. Immunol.
PD NOV
PY 2016
VL 138
IS 5
BP 1477
EP +
DI 10.1016/j.jaci.2016.06.001
PG 9
WC Allergy; Immunology
SC Allergy; Immunology
GA EE4AA
UT WOS:000389542700038
PM 27448445
ER
PT J
AU Kamoun, C
Morsheimer, M
Sullivan, KE
Holland, SM
Rundles, CC
Bunin, N
Heimall, JR
AF Kamoun, Camilia
Morsheimer, Megan
Sullivan, Kathleen E.
Holland, Steven M.
Rundles, Charlotte Cunningham
Bunin, Nancy
Heimall, Jennifer R.
TI Successful unrelated cord blood transplant for complete IFN-gamma
receptor 2 deficiency
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Letter
ID STEM-CELL TRANSPLANTATION; CHILD; SUSCEPTIBILITY
C1 [Kamoun, Camilia] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Morsheimer, Megan; Sullivan, Kathleen E.; Heimall, Jennifer R.] Childrens Hosp Philadelphia, Dept Pediat, Div Allergy & Immunol, Philadelphia, PA 19104 USA.
[Holland, Steven M.] NIAID, Lab Clin Infect Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Rundles, Charlotte Cunningham] Mt Sinai Sch Med, Dept Med, New York, NY USA.
[Bunin, Nancy] Childrens Hosp Philadelphia, Dept Pediat, Div Oncol, Philadelphia, PA 19104 USA.
RP Heimall, JR (reprint author), Childrens Hosp Philadelphia, Dept Pediat, Div Allergy & Immunol, Philadelphia, PA 19104 USA.
EM heimallj@email.chop.edu
NR 9
TC 0
Z9 0
U1 2
U2 2
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0091-6749
EI 1097-6825
J9 J ALLERGY CLIN IMMUN
JI J. Allergy Clin. Immunol.
PD NOV
PY 2016
VL 138
IS 5
BP 1489
EP +
DI 10.1016/j.jaci.2016.06.017
PG 5
WC Allergy; Immunology
SC Allergy; Immunology
GA EE4AA
UT WOS:000389542700042
PM 27522156
ER
PT J
AU Wang, YG
Hwangpo, T
Martin, MP
Vince, N
Qi, Y
Reynolds, RJ
Absher, D
Gao, XJ
Ballinger, CA
Burrows, PD
Atkinson, TP
Brown, EE
Elgavish, A
Liu, CR
Carrington, M
Schroeder, HW
AF Wang, Yuge
Hwangpo, Tracy
Martin, Maureen P.
Vince, Nicolas
Qi, Ying
Reynolds, Richard J.
Absher, Devin
Gao, Xiaojiang
Ballinger, Carol A.
Burrows, Peter D.
Atkinson, T. Prescott
Brown, Elizabeth E.
Elgavish, Ada
Liu, Cunren
Carrington, Mary
Schroeder, Harry W.
TI Killer cell immunoglobulin-like receptors are associated with common
variable immune deficiency pathogenesis
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Letter
ID SUSCEPTIBILITY; HLA; RECOGNITION; ARTHRITIS; GENES
C1 [Wang, Yuge; Burrows, Peter D.; Schroeder, Harry W.] Univ Alabama Birmingham, Dept Microbiol, Birmingham, AL 35294 USA.
[Wang, Yuge; Hwangpo, Tracy; Reynolds, Richard J.; Ballinger, Carol A.; Elgavish, Ada; Liu, Cunren; Schroeder, Harry W.] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA.
[Martin, Maureen P.; Qi, Ying; Gao, Xiaojiang; Carrington, Mary] Frederick Natl Lab Canc Res, Leidos Biomed Res, Expt Immunol Lab, Canc & Inflammat Program, Frederick, MD USA.
[Vince, Nicolas; Carrington, Mary] MIT & Harvard, Ragon Inst MGH, Cambridge, MA USA.
[Absher, Devin] HudsonAlpha Inst Biotechnol, Huntsville, AL USA.
[Atkinson, T. Prescott] Univ Alabama Birmingham, Dept Pediat, Birmingham, AL USA.
[Brown, Elizabeth E.] Univ Alabama Birmingham, Dept Pathol, Birmingham, AL 35294 USA.
RP Schroeder, HW (reprint author), Univ Alabama Birmingham, Dept Microbiol, Birmingham, AL 35294 USA.
EM hschroeder@uabmc.edu
FU CCR NIH HHS [HHSN261200800001C]; NCI NIH HHS [HHSN261200800001E]; NCRR
NIH HHS [M01 RR000032]; NIAID NIH HHS [R21 AI079741, T32 AI007051, U01
AI090902]; NIAMS NIH HHS [K01 AR060848]
NR 9
TC 0
Z9 0
U1 0
U2 0
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0091-6749
EI 1097-6825
J9 J ALLERGY CLIN IMMUN
JI J. Allergy Clin. Immunol.
PD NOV
PY 2016
VL 138
IS 5
BP 1495
EP 1498
DI 10.1016/j.jaci.2016.07.011
PG 5
WC Allergy; Immunology
SC Allergy; Immunology
GA EE4AA
UT WOS:000389542700045
PM 27665490
ER
PT J
AU Thomsen, IP
Smith, MA
Holland, SM
Creech, CB
AF Thomsen, Isaac P.
Smith, Meaghan A.
Holland, Steven M.
Creech, C. Buddy
TI A Comprehensive Approach to the Management of Children and Adults with
Chronic Granulomatous Disease
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY-IN PRACTICE
LA English
DT Review
DE Chronic granulomatous disease; Multidisciplinary care; IFN-gamma
ID STEM-CELL TRANSPLANTATION; MANIFESTATIONS; INFECTIONS; FEATURES;
CARRIERS; THERAPY; COLITIS
AB Chronic granulomatous disease (CGD), a disease characterized by inadequate neutrophil killing of microbial pathogens, affects 4 to 5 per million live births. For many decades following its description, CGD was a fatal disease in childhood. With the development of effective preventive therapies and the early recognition of infectious complications, 90% of children with CGD now survive into adulthood. The management of CGD in adults includes unique challenges and potential disease manifestations. In this article, the authors discuss the current approach to the management of CGD in both children and adults. This includes a focus on the importance of a comprehensive multidisciplinary approach in the care of CGD and its potential complications. In addition, a novel approach to improving education about CGD, and subsequently improving adherence to preventive therapies, is discussed. (C) 2016 American Academy of Allergy, Asthma & Immunology.
C1 [Thomsen, Isaac P.; Smith, Meaghan A.; Creech, C. Buddy] Vanderbilt Univ, Sch Med, Dept Pediat, Div Pediat Infect Dis,Vanderbilt Vaccine Res Prog, Nashville, TN 37212 USA.
[Holland, Steven M.] NIAID, Lab Clin Infect Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
RP Thomsen, IP (reprint author), D-7235 MCN,1161 21st Ave South, Nashville, TN 37232 USA.
EM isaac.thomsen@vanderbilt.edu
FU Horizon Pharma, plc.
FX This work was supported in part by an educational grant from Horizon
Pharma, plc.
NR 32
TC 1
Z9 1
U1 1
U2 1
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 2213-2198
EI 2213-2201
J9 J ALLER CL IMM-PRACT
JI J. Allergy Clin. Immunol.-Pract.
PD NOV-DEC
PY 2016
VL 4
IS 6
BP 1082
EP 1088
DI 10.1016/j.jaip.2016.03.021
PG 7
WC Allergy; Immunology
SC Allergy; Immunology
GA EE4ZA
UT WOS:000389613300007
PM 27178966
ER
PT J
AU Freeman, AF
Shah, NN
Parta, M
Su, HC
Brofferio, A
Gradus-Pizlo, I
Butty, S
Hughes, TE
Kleiner, DE
Avila, D
Heller, T
Kong, HH
Holland, SM
Hickstein, DD
AF Freeman, Alexandra F.
Shah, Nirali N.
Parta, Mark
Su, Helen C.
Brofferio, Alessandra
Gradus-Pizlo, Irma
Butty, Sabah
Hughes, Thomas E.
Kleiner, David E.
Avila, Daniele
Heller, Theo
Kong, Heidi H.
Holland, Steven M.
Hickstein, Dennis D.
TI Haploidentical related donor hematopoietic stem cell transplantation
with post-transplantation cyclophos phamide for DOCK8 deficiency
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY-IN PRACTICE
LA English
DT Letter
C1 [Freeman, Alexandra F.; Holland, Steven M.] NIAID, Lab Clin Infect Dis, NIH, Bldg 10,Room 12C103,9000 Rockville Pike, Bethesda, MD 20892 USA.
[Shah, Nirali N.] NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA.
[Parta, Mark] Leidos Biomedical Res Inc, Clin Res Directorate, Clin Monitoring Res Program, NCI Campus Frederick, Frederick, MD USA.
[Su, Helen C.] NIAID, Lab Host Def, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Brofferio, Alessandra] NHLBI, Cardiovasc Pulm Branch, NIH, Bldg 10, Bethesda, MD 20892 USA.
[Gradus-Pizlo, Irma; Butty, Sabah] Indiana Univ Sch Med, Indianapolis, IN 46202 USA.
[Hughes, Thomas E.] NIH, Clin Ctr Pharm Dept, Bldg 10, Bethesda, MD 20892 USA.
[Kleiner, David E.] NCI, Lab Pathol Branch, NIH, Bethesda, MD 20892 USA.
[Avila, Daniele; Hickstein, Dennis D.] NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA.
[Heller, Theo] NIDDK, Liver Dis Branch, NIH, Bethesda, MD USA.
[Kong, Heidi H.] NCI, Dermatol Branch, NIH, Bldg 10, Bethesda, MD 20892 USA.
RP Freeman, AF (reprint author), NIAID, Lab Clin Infect Dis, NIH, Bldg 10,Room 12C103,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM freemaal@mail.nih.gov
NR 9
TC 1
Z9 1
U1 0
U2 0
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 2213-2198
EI 2213-2201
J9 J ALLER CL IMM-PRACT
JI J. Allergy Clin. Immunol.-Pract.
PD NOV-DEC
PY 2016
VL 4
IS 6
BP 1239
EP +
DI 10.1016/j.jaip.2016.06.028
PG 5
WC Allergy; Immunology
SC Allergy; Immunology
GA EE4ZA
UT WOS:000389613300031
PM 27641484
ER
PT J
AU Torre, P
Hoffman, HJ
Springer, G
Cox, C
Young, MA
Margolick, JB
Plankey, M
AF Torre, Peter, III
Hoffman, Howard J.
Springer, Gayle
Cox, Christopher
Young, Mary A.
Margolick, Joseph B.
Plankey, Michael
TI Speech audiometry findings from HIV plus and HIV- adults in the MACS and
WIHS longitudinal cohort studies
SO JOURNAL OF COMMUNICATION DISORDERS
LA English
DT Article
DE HIV; Speech audiometry; Adults
ID MULTICENTER AIDS COHORT; WOMENS INTERAGENCY HIV; HEARING-LOSS;
SERONEGATIVE MEN; MANIFESTATIONS; HIV/AIDS
AB The purpose of this study was to compare various speech audiometry measures between HIV+ and HIV- adults and to further evaluate the association between speech audiometry and HIV disease variables in HIV+ adults only. Three hundred ninety-six adults from the Multicenter AIDS Cohort Study (MACS) and Women's Interagency HIV Study (WIHS) completed speech audiometry testing. There were 262 men, of whom 117 (44.7%) were HIV +, and 134 women, of whom 105 (78.4%) were HIV+. Speech audiometry was conducted as part of the standard clinical audiological evaluation that included otoscopy, tympanometry, and pure-tone air-and bone-conduction thresholds. Specific speech audiometry measures included speech recognition thresholds (SRT) and word recognition scores in quiet presented at 40 dB sensation level (SL) in reference to the SRT. SRT data were categorized in 5-dB steps from 0 to 25 dB hearing level (HL) with one category as >= 30 dB HL while word recognition scores were categorized as <90%, 90-99%, and 100%. A generalized estimating equations model was used to evaluate the association between HIV status and both ordinal outcomes. The SRT distributions across HIV+ and HIV- adults were similar. HIV+ and HIV adults had a similar percentages of word recognition scores <90%, a lower percentage of HIV- adults had 90-99%, but HIV adults had a higher percentage of 100%. After adjusting for covariables, HIV+ adults were borderline significantly more likely to have a higher SRT than HIV- adults (odds ratio PRI= 1.45, p = 0.06). Among HIV+ adults, HIV-related variables (i.e., CD4+ T-cell counts, HIV viral load, and ever history of clinical AIDS) were not significantly associated with either SRT or word recognition score data. There was, however, a ceiling effect for word recognition scores, probably the result of obtaining this measure in quiet with a relatively high presentation level. A more complex listening task, such as speech-in-noise testing, may be a more clinically informative test to evaluate the effects of HIV on speech communication. (C) 2016 Elsevier Inc. All rights reserved.
C1 [Torre, Peter, III] San Diego State Univ, Sch Speech Language & Hearing Sci, 5500 Campanile Dr,SLHS 244, San Diego, CA 92182 USA.
[Hoffman, Howard J.] NIDCD, Epidemiol & Stat Program, NIH, Bethesda, MD USA.
[Springer, Gayle; Cox, Christopher] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
[Young, Mary A.; Plankey, Michael] Georgetown Univ, Med Ctr, Div Infect Dis, Dept Med, Washington, DC 20007 USA.
[Margolick, Joseph B.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Mol Microbiol & Immunol, Baltimore, MD USA.
RP Torre, P (reprint author), San Diego State Univ, Sch Speech Language & Hearing Sci, 5500 Campanile Dr,SLHS 244, San Diego, CA 92182 USA.
EM ptorre@mail.sdsu.edu
FU National Institute on Deafness and Other Communication Disorders
(NIDCD), National Institutes of Health (NIH); National Institute of
Allergy and Infectious Diseases (NIAID), NIH [U01 AI-035042-18, U01
AI-034994-17]; NIAID [U01-AI-34994]; National Cancer Institute
[U01-AI-35042]; ICTR [UL1-RR025005]; Eunice Kennedy Shriver National
Institute of Child Health and Human Development (NICHD), NIH
[U01-HD-32632]
FX This research was supported by the National Institute on Deafness and
Other Communication Disorders (NIDCD), National Institutes of Health
(NIH) via interagency agreement with the National Institute of Allergy
and Infectious Diseases (NIAID), NIH for Cooperative Agreements U01
AI-035042-18 (MACS) and U01 AI-034994-17 (WIHS). Support of the
Baltimore-Washington, DC MACS site was provided by the NIAID, with
additional supplemental funding from the National Cancer Institute
(U01-AI-35042) and ICTR (UL1-RR025005). Support of the Metropolitan
Washington, DC WIHS site was provided by the NIAID (U01-AI-34994) and by
the Eunice Kennedy Shriver National Institute of Child Health and Human
Development (NICHD), NIH (U01-HD-32632).
NR 16
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 0021-9924
EI 1873-7994
J9 J COMMUN DISORD
JI J. Commun. Disord.
PD NOV-DEC
PY 2016
VL 64
BP 103
EP 109
DI 10.1016/j.jcomdis.2016.07.004
PG 7
WC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation
SC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation
GA EE4IQ
UT WOS:000389565900008
PM 27477593
ER
PT J
AU Bottomley, A
Pe, M
Sloan, J
Basch, E
Bonnetain, F
Calvert, M
Campbell, A
Cleeland, C
Cocks, K
Collette, L
Dueck, AC
Devlin, N
Flechtner, HH
Gotay, C
Greimel, E
Griebsch, I
Groenvold, M
Hamel, JF
King, M
Kluetz, PG
Koller, M
Malone, DC
Martinelli, F
Mitchell, SA
Moinpour, CM
Musoro, J
O'Connor, D
Oliver, K
Piault-Louis, E
Piccart, M
Pimentel, FL
Quinten, C
Reijneveld, JC
Schurmann, C
Smith, AW
Soltys, KM
Taphoorn, MJB
Velikova, G
Coens, C
AF Bottomley, Andrew
Pe, Madeline
Sloan, Jeff
Basch, Ethan
Bonnetain, Franck
Calvert, Melanie
Campbell, Alicyn
Cleeland, Charles
Cocks, Kim
Collette, Laurence
Dueck, Amylou C.
Devlin, Nancy
Flechtner, Hans-Henning
Gotay, Carolyn
Greimel, Eva
Griebsch, Ingolf
Groenvold, Mogens
Hamel, Jean-Francois
King, Madeleine
Kluetz, Paul G.
Koller, Michael
Malone, Daniel C.
Martinelli, Francesca
Mitchell, Sandra A.
Moinpour, Carol M.
Musoro, Jammbe
O'Connor, Daniel
Oliver, Kathy
Piault-Louis, Elisabeth
Piccart, Martine
Pimentel, Francisco L.
Quinten, Chantal
Reijneveld, Jaap C.
Schuermann, Christoph
Smith, Ashley Wilder
Soltys, Katherine M.
Taphoorn, Martin J. B.
Velikova, Galina
Coens, Corneel
CA Setting Int Stand Analyzing
TI Analysing data from patient-reported outcome and quality of life
endpoints for cancer clinical trials: a start in setting international
standards
SO LANCET ONCOLOGY
LA English
DT Article
ID EVEROLIMUS PLUS EXEMESTANE; BREAST-CANCER
AB Measures of health-related quality of life (HRQOL) and other patient-reported outcomes generate important data in cancer randomised trials to assist in assessing the risks and benefits of cancer therapies and fostering patient-centred cancer care. However, the various ways these measures are analysed and interpreted make it difficult to compare results across trials, and hinders the application of research findings to inform publications, product labelling, clinical guidelines, and health policy. To address these problems, the Setting International Standards in Analyzing Patient-Reported Outcomes and Quality of Life Endpoints Data (SISAQOL) initiative has been established. This consortium, directed by the European Organisation for Research and Treatment of Cancer (EORTC), was convened to provide recommendations on how to standardise the analysis of HRQOL and other patient-reported outcomes data in cancer randomised trials. This Personal View discusses the reasons why this project was initiated, the rationale for the planned work, and the expected benefits to cancer research, patient and provider decision making, care delivery, and policy making.
C1 [Bottomley, Andrew; Pe, Madeline; Collette, Laurence; Martinelli, Francesca; Musoro, Jammbe; Coens, Corneel] EORTC Headquarters, 83-11 Ave E Mounier, B-1200 Brussels, Belgium.
[Sloan, Jeff] Mayo Clin, Alliance Stat & Data Ctr, Rochester, MN USA.
[Basch, Ethan] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC USA.
[Bonnetain, Franck] Univ Hosp Besancon, Methodol & Qual Life Unit Canc, INSERM, U1098, Besancon, France.
[Calvert, Melanie] Univ Birmingham, Coll Med & Dent Sci, Inst Appl Hlth Res, Ctr Patient Reported Outcomes Res, Birmingham, W Midlands, England.
[Campbell, Alicyn; Piault-Louis, Elisabeth] Genentech Inc, San Francisco, CA USA.
[Cleeland, Charles] Univ Texas MD Anderson Canc Ctr, Dept Symptom Res, Houston, TX 77030 USA.
[Cocks, Kim] Adelphi Values, Bollington, Cheshire, England.
[Dueck, Amylou C.] Mayo Clin, Alliance Stat & Data Ctr, Scottsdale, AZ USA.
[Devlin, Nancy] Off Hlth Econ, London, England.
[Flechtner, Hans-Henning] Univ Magdeburg, Clin Child & Adolescent Psychiat & Psychotherapy, Magdeburg, Germany.
[Gotay, Carolyn] Univ British Columbia, Sch Populat & Publ Hlth, Vancouver, BC, Canada.
[Greimel, Eva] Med Univ Graz, Obstet & Gynecol, Graz, Austria.
[Griebsch, Ingolf] Boehringer Ingelheim GmbH & Co KG, Frankfurt, Germany.
[Groenvold, Mogens] Univ Copenhagen, Dept Publ Hlth, Copenhagen, Denmark.
[Groenvold, Mogens] Univ Copenhagen, Bispebjerg Hosp, Copenhagen, Denmark.
[Hamel, Jean-Francois] Univ Hosp Angers UNAM, Methodol & Biostat Dept, Angers, France.
[King, Madeleine] Univ Sydney, Sch Psychol, Sydney, NSW, Australia.
[King, Madeleine] Univ Sydney, Sydney Med Sch, Sydney, NSW, Australia.
[Kluetz, Paul G.] US FDA, Off Hematol & Oncol Prod, Ctr Drug Evaluat & Res, Silver Spring, MD USA.
[Koller, Michael] Univ Hosp Regensburg, Ctr Clin Studies, Regensburg, Germany.
[Malone, Daniel C.] Univ Arizona, Coll Pharm, Tucson, AZ 85721 USA.
[Mitchell, Sandra A.; Smith, Ashley Wilder] NCI, Outcomes Res Branch, Healthcare Delivery Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Moinpour, Carol M.] Fred Hutchinson Canc Res Ctr, 1124 Columbia St, Seattle, WA 98104 USA.
[O'Connor, Daniel] Med & Healthcare Prod Regulatory Agcy, London, England.
[Oliver, Kathy] Int Brain Tumour Alliance, Tadworth, Surrey, England.
[Piccart, Martine] Inst Jules Bordet, Internal Med Oncol, Brussels, Belgium.
[Pimentel, Francisco L.] Univ Aveiro, Hlth Sci, Aveiro, Portugal.
[Pimentel, Francisco L.] Lenitudes Med Ctr & Res, Santa Maria Feira, Portugal.
[Quinten, Chantal] European Ctr Dis Prevent & Control, Surveillance & Response Support Unit, Epidemiol Methods Sect, Stockholm, Sweden.
[Reijneveld, Jaap C.] Vrije Univ Amsterdam Med Ctr, Dept Neurol, Amsterdam, Netherlands.
[Reijneveld, Jaap C.] Vrije Univ Amsterdam Med Ctr, Brain Tumor Ctr, Amsterdam, Netherlands.
[Schuermann, Christoph] Inst Qual & Efficiency Hlth Care, Cologne, Germany.
[Soltys, Katherine M.] Hlth Canada, Ottawa, ON, Canada.
[Taphoorn, Martin J. B.] Leiden Univ, Med Ctr, Leiden, Netherlands.
[Taphoorn, Martin J. B.] Med Ctr Haaglanden, The Hague, Netherlands.
[Velikova, Galina] Univ Leeds, St Jamess Hosp, Leeds Inst Canc & Pathol, Leeds, W Yorkshire, England.
RP Bottomley, A (reprint author), EORTC Headquarters, 83-11 Ave E Mounier, B-1200 Brussels, Belgium.
EM andrew.bottomley@eortc.be
OI Pimentel, Francisco Luis/0000-0001-5993-5132
FU Boehringer Ingelheim GmbH; EORTC Cancer Research Fund; Fonds Cancer
(FOCA) from Belgium
FX EORTC received an unrestricted education grant from Boehringer Ingelheim
GmbH to initiate this work and additional financial support was provided
by the EORTC Cancer Research Fund and Fonds Cancer (FOCA) from Belgium.
Andrew Bottomley confirms final responsibility for the decision to
submit for publication. This publication reflects the views of the
individual authors and should not be construed to represent official
views or policies of the US Food and Drug Administration, US National
Cancer Institute, Medicines and Healthcare products Regulatory Agency,
or Health Canada.
NR 26
TC 1
Z9 1
U1 2
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1470-2045
EI 1474-5488
J9 LANCET ONCOL
JI Lancet Oncol.
PD NOV
PY 2016
VL 17
IS 11
BP E510
EP E514
DI 10.1016/S1470-2045(16)30510-1
PG 5
WC Oncology
SC Oncology
GA EE3YF
UT WOS:000389537600021
PM 27769798
ER
PT J
AU Lau, MWL
Ferre-D'Amare, AR
AF Lau, Matthew W. L.
Ferre-D'Amare, Adrian R.
TI Many Activities, One Structure: Functional Plasticity of Ribozyme Folds
SO MOLECULES
LA English
DT Review
DE ribozyme; in vitro selection; fitness landscape
ID GLMS RIBOZYME; INTERVENING SEQUENCE; NUCLEOTIDE SYNTHESIS; RNA;
SELECTION; BINDING; TETRAHYMENA; RIBOSWITCH; PROTEIN;
GLUCOSAMINE-6-PHOSPHATE
AB Catalytic RNAs, or ribozymes, are involved in a number of essential biological processes, such as replication of RNA genomes and mobile genetic elements, RNA splicing, translation, and RNA degradation. The function of ribozymes requires the formation of active sites decorated with RNA functional groups within defined three-dimensional (3D) structures. The genotype (sequence) of RNAs ultimately determines what 3D structures they adopt (as a function of their environmental conditions). These 3D structures, in turn, give rise to biochemical activity, which can further elaborate them by catalytic rearrangements or association with other molecules. The fitness landscape of a non-periodic linear polymer, such as RNA, relates its primary structure to a phenotype. Two major challenges in the analysis of ribozymes is to map all possible genotypes to their corresponding catalytic activity (that is, to determine their fitness landscape experimentally), and to understand whether their genotypes and three-dimensional structures can support multiple different catalytic functions. Recently, the combined results of experiments that employ in vitro evolution methods, high-throughput sequencing and crystallographic structure determination have hinted at answers to these two questions: while the fitness landscape of ribozymes is rugged, meaning that their catalytic activity cannot be optimized by a smooth trajectory in sequence space, once an RNA achieves a stable three-dimensional fold, it can be endowed with distinctly different biochemical activities through small changes in genotype. This functional plasticity of highly structured RNAs may be particularly advantageous for the adaptation of organisms to drastic changes in selective pressure, or for the development of new biotechnological tools.
C1 [Lau, Matthew W. L.; Ferre-D'Amare, Adrian R.] NHLBI, 50 South Dr,MSC 8012, Bethesda, MD 20892 USA.
RP Ferre-D'Amare, AR (reprint author), NHLBI, 50 South Dr,MSC 8012, Bethesda, MD 20892 USA.
EM matt.wl.lau@gmail.com; adrian.ferre@nih.gov
FU National Heart, Lung and Blood Institute, National Institutes of Health
FX We thank J.N. Pitt for discussions. This work was supported in part by
the intramural program of the National Heart, Lung and Blood Institute,
National Institutes of Health. M.W.L. was a Croucher Foundation
Post-doctoral Fellow.
NR 40
TC 1
Z9 1
U1 8
U2 8
PU MDPI AG
PI BASEL
PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND
SN 1420-3049
J9 MOLECULES
JI Molecules
PD NOV
PY 2016
VL 21
IS 11
AR 1570
DI 10.3390/molecules21111570
PG 8
WC Chemistry, Organic
SC Chemistry
GA EE9AO
UT WOS:000389918200150
ER
PT J
AU Lizardo, MM
Morrow, JJ
Miller, TE
Hong, ES
Ren, L
Mendoza, A
Halsey, CH
Scacheri, PC
Helman, LJ
Khanna, C
AF Lizardo, Michael M.
Morrow, James J.
Miller, Tyler E.
Hong, Ellen S.
Ren, Ling
Mendoza, Arnulfo
Halsey, Charles H.
Scacheri, Peter C.
Helman, Lee J.
Khanna, Chand
TI Upregulation of Glucose-Regulated Protein 78 in Metastatic Cancer Cells
Is Necessary for Lung Metastasis Progression
SO NEOPLASIA
LA English
DT Article
ID ENDOPLASMIC-RETICULUM STRESS; BREAST-CANCER; TUMOR; GRP78; OSTEOSARCOMA;
RESISTANCE; APOPTOSIS; IDENTIFICATION; MECHANISM; CHAPERONE
AB Metastasis is the cause of more than 90% of all cancer deaths. Despite this fact, most anticancer therapeutics currently in clinical use have limited efficacy in treating established metastases. Here, we identify the endoplasmic reticulum chaperone protein, glucose-regulated protein 78 (GRP78), as a metastatic dependency in several highly metastatic cancer cell models. We find that GRP78 is consistently upregulated when highly metastatic cancer cells colonize the lung microenvironment and that mitigation of GRP78 upregulation via short hairpin RNA or treatment with the small molecule IT-139, which is currently under clinical investigation for the treatment of primary tumors, inhibits metastatic growth in the lung microenvironment. Inhibition of GRP78 upregulation and an associated reduction in metastatic potential have been shown in four highly metastatic cell line models: three human osteosarcomas and one murine mammary adenocarcinoma. Lastly, we show that downmodulation of GRP78 in highly metastatic cancer cells significantly increases median survival times in our in vivo animal model of experimental metastasis. Collectively, our data indicate that GRP78 is an attractive target for the development of antimetastatic therapies.
C1 [Lizardo, Michael M.; Hong, Ellen S.; Mendoza, Arnulfo; Helman, Lee J.; Khanna, Chand] NCI, Pediat Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Morrow, James J.; Miller, Tyler E.; Scacheri, Peter C.] Case Western Reserve Univ, Sch Med, Dept Genet & Genome Sci, Cleveland, OH USA.
[Morrow, James J.; Miller, Tyler E.] Case Western Reserve Univ, Dept Pathol, Cleveland, OH 44106 USA.
[Ren, Ling] NCI, Comparat Oncol Program, NIH, Bethesda, MD 20892 USA.
[Halsey, Charles H.] NCI, Lab Canc Biol & Genet, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Khanna, Chand] Ethos Discovery, Washington, DC 20009 USA.
[Khanna, Chand] Ethos Vet Hlth, Wolburn, MA 01801 USA.
RP Khanna, C (reprint author), Ethos Discovery, Washington, DC 20009 USA.; Khanna, C (reprint author), Ethos Vet Hlth, Wolburn, MA 01801 USA.
EM ckhanna@animalci.com
FU Intramural Research Program of the National Institutes of Health, Center
for Cancer Research, Pediatric Oncology Branch; National Institutes of
Health [15335, T32GM007250]; National Institutes of Health/National
Cancer Institute [F30 CA186633, CA183510]; [RO1CA160356]
FX This research was supported (in part) by the Intramural Research Program
of the National Institutes of Health, Center for Cancer Research,
Pediatric Oncology Branch. M.M.L. was supported by National Institutes
of Health Intramural Visiting Fellow Program(award 15335), J.J.M. and
T.E.M. were funded by National Institutes of Health T32GM007250. J.J.M.
and T.E.M. were also funded by National Institutes of Health/National
Cancer Institute F30 CA186633 and CA183510, respectively. P.C.S.
received grant support RO1CA160356.
NR 36
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 1476-5586
J9 NEOPLASIA
JI Neoplasia
PD NOV
PY 2016
VL 18
IS 11
BP 699
EP 710
DI 10.1016/j.neo.2016.09.001
PG 12
WC Oncology
SC Oncology
GA EE3TC
UT WOS:000389520300006
PM 27973325
ER
PT J
AU Yee, LM
Sandoval, G
Bailit, J
Reddy, UM
Wapner, RJ
Varner, MW
Caritis, SN
Prasad, M
Tita, ATN
Saade, G
Sorokin, Y
Rouse, DJ
Blackwell, SC
Tolosa, JE
AF Yee, Lynn M.
Sandoval, Grecio
Bailit, Jennifer
Reddy, Uma M.
Wapner, Ronald J.
Varner, Michael W.
Caritis, Steve N.
Prasad, Mona
Tita, Alan T. N.
Saade, George
Sorokin, Yoram
Rouse, Dwight J.
Blackwell, Sean C.
Tolosa, Jorge E.
CA Eunice Kennedy Shriver Natl Inst
TI Maternal and Neonatal Outcomes With Early Compared With Delayed Pushing
Among Nulliparous Women
SO OBSTETRICS AND GYNECOLOGY
LA English
DT Article
ID CONTINUOUS EPIDURAL ANALGESIA; PERINATAL OUTCOMES; 2ND-STAGE; LABOR;
DURATION; MANAGEMENT; MIDWIFERY; TRIAL; CARE
AB OBJECTIVE: To describe factors associated with delayed pushing and evaluate the relationship between delayed pushing and perinatal outcomes in nulliparous women with singleton term gestations.
METHODS: This was a secondary analysis of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Assessment of Perinatal Excellence cohort of 115,502 women and their neonates born in 25 U.S. hospitals from 2008 to 2011. Nulliparous women with singleton, cephalic, nonanomalous term births who achieved 10-cm cervical dilation were included. Women in whom pushing was delayed by 60 minutes or greater (delayed group) were compared with those who initiated pushing within 30 minutes (early group). Multivariable regression analyses were used to assess the independent association of delayed pushing with mode of delivery, length of the second stage, and other maternal and perinatal outcomes (significance defined as P<.05).
RESULTS: Of 21,034 women in the primary analysis sample, pushing was delayed in 18.4% (n=3,870). Women who were older, privately insured, or non-Hispanic white as well as those who had induction or augmentation of labor, diabetes, or epidural analgesia were more likely to have delayed pushing. Delayed pushing was more common when the second stage began during daytime hours or in hospitals with dedicated 24-hour obstetric anesthesia, although differences were small. After adjusting for differences in baseline and labor characteristics including center, women in the delayed group had longer mean durations of the second stage (191 compared with 84 minutes, P<.001) and of active pushing (86 compared with 76 minutes, P<.001). Delayed pushing was associated with greater rates of cesarean delivery (11.2% compared with 5.1%; adjusted odds ratio [OR] 1.86, 95% confidence interval [CI] 1.63-2.12), operative vaginal delivery (adjusted OR 1.26, 95% CI 1.14-1.40), postpartum hemorrhage (adjusted OR 1.43, 95% CI 1.05-1.95), and blood transfusion (adjusted OR 1.51, 95% CI 1.04-2.17). Delayed pushing was not associated with increased odds of adverse neonatal outcomes compared with early pushing.
CONCLUSION: In this large birth cohort, delayed pushing was associated with longer second stage duration, increased odds of cesarean delivery, and increased odds of postpartum hemorrhage, but was not associated with neonatal morbidity.
C1 Northwestern Univ, Dept Obstet, Chicago, IL 60611 USA.
Northwestern Univ, Dept Gynecol, Chicago, IL 60611 USA.
Case Western Reserve Univ, Metrohlth Med Ctr, Cleveland, OH USA.
Columbia Univ, New York, NY USA.
Univ Utah, Hlth Sci Ctr, Salt Lake City, UT USA.
Univ Pittsburgh, Pittsburgh, PA USA.
Ohio State Univ, Columbus, OH 43210 USA.
Univ Alabama Birmingham, Birmingham, AL USA.
Wayne State Univ, Detroit, MI USA.
Brown Univ, Providence, RI 02912 USA.
Univ Texas Hlth Sci Ctr Houston, Childrens Mem Hermann Hosp, Houston, TX 77030 USA.
Oregon Hlth & Sci Univ, Portland, OR 97201 USA.
George Washington Univ, Ctr Biostat, Washington, DC USA.
Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA.
RP Yee, LM (reprint author), Northwestern Univ, Feinberg Sch Med, Dept Obstet & Gynecol, Div Maternal Fetal Med, 250 E Super St,5-2191, Chicago, IL 60611 USA.
EM lynn.yee@northwestern.edu
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development (NICHD) [HD21410, HD27869, HD27915, HD27917, HD34116,
HD34208, HD36801, HD40500, HD40512, HD40544, HD40545, HD40560, HD40485,
HD53097, HD53118]; National Center for Research Resources [UL1 RR024989,
5UL1 RR025764]
FX The project described was supported by grants from the Eunice Kennedy
Shriver National Institute of Child Health and Human Development (NICHD)
(HD21410, HD27869, HD27915, HD27917, HD34116, HD34208, HD36801, HD40500,
HD40512, HD40544, HD40545, HD40560, HD40485, HD53097, HD53118) and the
National Center for Research Resources (UL1 RR024989, 5UL1 RR025764).
NR 19
TC 1
Z9 1
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0029-7844
J9 OBSTET GYNECOL
JI Obstet. Gynecol.
PD NOV
PY 2016
VL 128
IS 5
BP 1039
EP 1047
DI 10.1097/AOG.0000000000001683
PG 9
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA EE0GA
UT WOS:000389251000020
PM 27741203
ER
PT J
AU Domalpally, A
Danis, R
Agorn, E
Blodi, B
Clemons, T
Chew, E
AF Domalpally, Amitha
Danis, Ronald
Agorn, Elvira
Blodi, Barbara
Clemons, Traci
Chew, Emily
CA Age-Related Eye Dis Study Res Grp
TI Evaluation of Geographic Atrophy from Color Photographs and Fundus
Autofluorescence Images Age-Related Eye Disease Study 2 Report Number 11
SO OPHTHALMOLOGY
LA English
DT Article
ID RETINAL-PIGMENT EPITHELIUM; VISUAL-ACUITY LOSS; MACULAR DEGENERATION;
NATURAL-HISTORY; CLINICAL-TRIALS; PROGRESSION; OPHTHALMOSCOPE;
ENLARGEMENT; PATTERNS; RATES
AB Purpose: To compare measurements of area of geographic atrophy (GA) and change in GA area from color photographs and fundus autofluorescence (FAF) images.
Design: The Age-Related Eye Disease Study 2 (AREDS2) was a prospective multicenter randomized clinical trial evaluating progression of dry age-related macular degeneration (AMD) using color photographs at annual visits over a 5-year study period. The FAF images were acquired in a subset of participants who joined the FAF ancillary study at any of the annual visits over the study period.
Participants: The AREDS2 FAF ancillary study included 8070 corresponding color and FAF visits of 2202 participants with variable follow-up.
Methods: Corresponding color and FAF images were independently evaluated at a central reading center for GA area measurement, lesion growth, and involvement of the macula center.
Main Outcome Measures: Presence, area, growth rate of GA, and involvement of center of macula from color and FAF images.
Results: Hypoautofluorescence was visible in 2048 visits (25.4%). Agreement for the presence of GA between the 2 modalities had a kappa of 0.79, with 23% of visits with hypoautofluorescence not presenting with GA on color photographs. Percentage agreement for GA presence ranged from 43% at baseline to 81% at year 5 with improving agreement over time. The mean difference in GA area between the 2 modalities was 0.5 mm(2), with larger areas on FAF. Growth rate of GA was 1.45 mm(2) from color photographs and 1.43 mm2 from FAF images. The center of the macula was involved in 51% of color photographs and 56% with FAF images.
Conclusions: Geographic atrophy may be detected earlier by the use of FAF images, but over the course of the study, the 2 modalities become comparable. Progression of GA area is comparable between color photographs and FAF images, but evaluating involvement of the center of the macula may differ, probably because of macular pigmentation blocking autofluorescence. (C) 2016 by the American Academy of Ophthalmology.
C1 [Domalpally, Amitha; Danis, Ronald; Blodi, Barbara] Univ Wisconsin, Fundus Photograph Reading Ctr, Madison, WI USA.
[Clemons, Traci] EMMES Corp, Rockville, MD USA.
[Agorn, Elvira; Chew, Emily] NEI, Bethesda, MD 20892 USA.
RP Domalpally, A (reprint author), Univ Wisconsin, Fundus Photograph Reading Ctr, Dept Ophthalmol & Visual Sci, 2828 Marshall Court,Suite 200, Madison, WI 53705 USA.
EM adomalpally@rc.ophth.wisc.edu
OI Domalpally, Amitha/0000-0002-8145-9619
FU National Eye Institute [HHS-N-260-2005-00007-C]; Research to Prevent
Blindness
FX The author(s) have made the following disclosure(s): A.D., R.D., E.A.,
B.B., E.C. and T.C.: Grant National Eye Institute grant no.
HHS-N-260-2005-00007-C (TEC). Supported in part by an unrestricted grant
from Research to Prevent Blindness to the Department of Ophthalmology
and Visual Sciences, University of Wisconsin-Madison (A.D., R.D., and
B.B.).
NR 35
TC 1
Z9 1
U1 1
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0161-6420
EI 1549-4713
J9 OPHTHALMOLOGY
JI Ophthalmology
PD NOV
PY 2016
VL 123
IS 11
BP 2401
EP 2407
DI 10.1016/j.ophtha.2016.06.025
PG 7
WC Ophthalmology
SC Ophthalmology
GA EE3QK
UT WOS:000389509500025
PM 27448832
ER
PT J
AU Colin, VM
Auperin, A
Pillon, M
Burke, A
Anderson, J
Barkausk, D
Wheatley, K
Delgado, R
Alexander, S
Uyttebroeck, A
Bollard, C
Zsiros, J
Csoka, M
Goma, G
Tulard, A
Patte, C
Gross, T
AF Colin, V. Minard
Auperin, A.
Pillon, M.
Burke, A.
Anderson, J.
Barkausk, D.
Wheatley, K.
Delgado, R.
Alexander, S.
Uyttebroeck, A.
Bollard, C.
Zsiros, J.
Csoka, M.
Goma, G.
Tulard, A.
Patte, C.
Gross, T.
TI Results of the Randomized Intergroup Trial Inter-B-NHL RITUX 2010 for
Children/Adolescents with High-Risk B-Cell Non Hodgkin Lymphoma (B-NHL)
and Mature Acute Leukemia (B-AL)
SO PEDIATRIC BLOOD & CANCER
LA English
DT Meeting Abstract
C1 [Colin, V. Minard; Auperin, A.; Goma, G.; Tulard, A.; Patte, C.] Gustave Roussy, Paediat, Villejuif, France.
[Pillon, M.] Univ Padua, Clin Oncoematol Paediat, Padua, Italy.
[Burke, A.] Addenbrookes NHS Trust, Childrens Serv, Cambridge, England.
[Anderson, J.] Merck Res Labs, Oncol, N Wales, PA USA.
[Barkausk, D.] Univ Southern Calif, Keck Sch Med, Dept Prevent Med, Biostat Div, Los Angeles, CA USA.
[Wheatley, K.] Sch Canc Sci, Canc Res UK Clin Trials Unit, Birmingham, W Midlands, England.
[Delgado, R.] Dept Pediat, Valencia, Spain.
[Alexander, S.] Hosp Sick Child, Div Haematol Oncol, Toronto, ON, Canada.
[Uyttebroeck, A.] Univ Hosp Leuven, Dept Paediat Haematooncol, Leuven, Belgium.
[Bollard, C.] Main Hosp, Allergy & Immunol, Washington, DC USA.
[Zsiros, J.] Univ Amsterdam, Emma Childrens Hosp, Dept Paediat Oncol, Amsterdam, Netherlands.
[Csoka, M.] Semmelweis Univ, Dept Paediat 2, Budapest, Hungary.
[Gross, T.] NCI, NIH, DHHS, Ctr Global Hlth, Rockville, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1545-5009
EI 1545-5017
J9 PEDIATR BLOOD CANCER
JI Pediatr. Blood Cancer
PD NOV
PY 2016
VL 63
SU 3
MA O-104
BP S31
EP S31
PG 1
WC Oncology; Hematology; Pediatrics
SC Oncology; Hematology; Pediatrics
GA DY0XF
UT WOS:000384818800439
ER
EF