FN Thomson Reuters Web of Science™
VR 1.0
PT J
AU Majerciak, V
Lu, M
Li, XF
Zheng, ZM
AF Majerciak, Vladimir
Lu, Mathew
Li, Xiaofan
Zheng, Zhi-Ming
TI Attenuation of the suppressive activity of cellular splicing factor
SRSF3 by Kaposi sarcoma-associated herpesvirus ORF57 protein is required
for RNA splicing
SO RNA-A PUBLICATION OF THE RNA SOCIETY
LA English
DT Article
DE SRSF3; alternative splicing; RNA processing; ORF57; KSHV
ID PRE-MESSENGER-RNA; EPITHELIAL OVARIAN-CANCER; SR PROTEINS; FACTOR SRP20;
PROTEOMIC ANALYSIS; EXPORT FACTOR; NUCLEAR-RNA; VIRUS; EXPRESSION;
INTERACTS
AB Kaposi sarcoma-associated herpesvirus (KSHV) ORF57 is a multifunctional post-transcriptional regulator essential for viral gene expression during KSHV lytic infection. ORF57 requires interactions with various cellular proteins for its function. Here, we identified serine/arginine-rich splicing factor 3 (SRSF3, formerly known as SRp20) as a cellular cofactor involved in ORF57-mediated splicing of KSHV K8 beta RNA. In the absence of ORF57, SRSF3 binds to a suboptimal K8 beta intron and inhibits K8 beta splicing. Knockdown of SRSF3 promotes K8 beta splicing, mimicking the effect of ORF57. The N-terminal half of ORF57 binds to the RNA recognition motif of SRSF3, which prevents SRSF3 from associating with the K8 beta intron RNA and therefore attenuates the suppressive effect of SRSF3 on K8 beta splicing. ORF57 also promotes splicing of heterologous non-KSHV transcripts that are negatively regulated by SRSF3, indicating that the effect of ORF57 on SRSF3 activity is independent of RNA target. SPEN proteins, previously identified as ORF57-interacting partners, suppress ORF57 splicing activity by displacing ORF57 from SRSF3-RNA complexes. In summary, we have identified modulation of SRSF3 activity as the molecular mechanism by which ORF57 promotes RNA splicing.
C1 [Majerciak, Vladimir; Lu, Mathew; Li, Xiaofan; Zheng, Zhi-Ming] NCI, Tumor Virus RNA Biol Sect, Gene Regulat & Chromosome Biol Lab, Ctr Canc Res,NIH, Frederick, MD 21702 USA.
RP Zheng, ZM (reprint author), NCI, Tumor Virus RNA Biol Sect, Gene Regulat & Chromosome Biol Lab, Ctr Canc Res,NIH, Frederick, MD 21702 USA.
EM zhengt@exchange.nih.gov
FU intramural research program of the National Cancer Institute of the
National Institutes of Health
FX We thank Michael Kruhlak of NCI for his help with confocal microscopy
and Barbara Felber of NCI for providing the RBM15 and OTT3 constructs.
This work was supported by the intramural research program of the
National Cancer Institute of the National Institutes of Health.
NR 59
TC 12
Z9 12
U1 1
U2 5
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-Publ. RNA Soc.
PD NOV
PY 2014
VL 20
IS 11
BP 1747
EP 1758
DI 10.1261/rna.045500.114
PG 12
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA AS1UA
UT WOS:000344065900010
PM 25234929
ER
PT J
AU Luby, M
Warach, SJ
Nadareishvili, Z
Merino, JG
AF Luby, Marie
Warach, Steven J.
Nadareishvili, Zurab
Merino, Jose G.
TI Immediate Changes in Stroke Lesion Volumes Post Thrombolysis Predict
Clinical Outcome
SO STROKE
LA English
DT Article
DE perfusion imaging; thrombolytic therapy
ID ACUTE ISCHEMIC-STROKE; TISSUE-PLASMINOGEN ACTIVATOR; INTRAVENOUS
THROMBOLYSIS; DIFFUSION; PERFUSION; REVERSAL; MRI; INFARCTION; RECOVERY;
TRIAL
AB Background and Purpose We hypothesize that reversal in diffusion-weighted imaging (DWI) volume at 24 hours predicts favorable clinical outcome only if accompanied by immediate reperfusion. Our aim was to quantify the immediate DWI and mean transit time changes at 2 and 24 hours after intravenous tissue-type plasminogen activator to evaluate the effect of reperfusion and DWI change on outcome.
Methods Patients were selected from the Lesion Evolution in Stroke and Ischemia On Neuroimaging Project if they had an acute MRI with evaluable DWI and perfusion-weighted imaging, were treated with standard intravenous tissue-type plasminogen activator, had post-thrombolysis MRI with evaluable DWI and perfusion-weighted imaging at 2 and 24 hours and had follow-up fluid attenuated inversion recovery MRI at discharge through 90 days. A reader measured the DWI, mean transit time, and fluid attenuated inversion recovery volumes using a validated technique. A vascular neurologist scored the National Institutes of Health Stroke Scale at admit, 2, and 24 hours and the modified Rankin Scale at discharge, 5, 30, and 90 days. Favorable clinical outcome was defined as modified Rankin Scale of 0 or 1.
Results Seventy-one patients met the study criteria with mean (SD) age of 71.6 (+/- 16.4) years, 58% women, median admit National Institutes of Health Stroke Scale 9 (interquartile range, 4-18), median onset to triage 45 minutes (30-65), and median first MRI to intravenous tissue-type plasminogen activator 47 minutes (39-59). In binary multiple logistic regression analysis, younger age (odds ratio, 1.165; P=0.014; 95% confidence interval [CI], 1.031-1.316), lower admit National Institutes of Health Stroke Scale (odds ratio, 1.221; P=0.012; 95% confidence interval, 1.045-1.427), decrease in mean transit time volume at 2 hours (odds ratio, 1.021; P=0.031; 95% confidence interval, 1.002-1.040), and decrease in DWI volume at 24 hours (odds ratio, 1.173; P=0.027; 95% confidence interval, 1.018-1.351) were significant predictors of favorable clinical outcome.
Conclusions Reversal of the DWI volume at 24 hours because of immediate reperfusion in patients post thrombolysis is predictive of favorable clinical outcome.
C1 [Luby, Marie; Warach, Steven J.; Nadareishvili, Zurab; Merino, Jose G.] NINDS, Sect Stroke Diagnost & Therapeut, Bethesda, MD 20892 USA.
[Warach, Steven J.] Seton Univ Texas Southwestern, Dept Neurol & Neurotherapeut, Austin, TX USA.
[Nadareishvili, Zurab; Merino, Jose G.] Johns Hopkins Community Phys, Bethesda, MD USA.
RP Luby, M (reprint author), NINDS, Stroke Branch, NIH, Stroke Program, 10 Ctr Dr,Room B1D-733,MSC 1063, Bethesda, MD 20892 USA.
EM lubym@ninds.nih.gov
OI Merino, Jose/0000-0002-6676-0008
FU National Institutes of Health
FX This work was supported by the National Institutes of Health.
NR 18
TC 6
Z9 6
U1 0
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0039-2499
EI 1524-4628
J9 STROKE
JI Stroke
PD NOV
PY 2014
VL 45
IS 11
BP 3275
EP 3279
DI 10.1161/STROKEAHA.114.006082
PG 5
WC Clinical Neurology; Peripheral Vascular Disease
SC Neurosciences & Neurology; Cardiovascular System & Cardiology
GA AS6CD
UT WOS:000344351500034
PM 25213340
ER
PT J
AU Mandrup, S
MacDougald, OA
Moss, J
Ntambi, J
Pekala, P
Tang, QQ
Wolfgang, M
Bernlohr, DA
AF Mandrup, Susanne
MacDougald, Ormond A.
Moss, Joel
Ntambi, James
Pekala, Phillip
Tang, Qi-Qun
Wolfgang, Michael
Bernlohr, David A.
TI In memoriam: M. Daniel Lane, 1930-2014 (vol 25, pg 437, 2014)
SO TRENDS IN ENDOCRINOLOGY AND METABOLISM
LA English
DT Correction
C1 [Mandrup, Susanne] Univ Southern Denmark, Dept Biochem & Mol Biol, Odense, Denmark.
[MacDougald, Ormond A.] Univ Michigan, Dept Mol & Integrat Physiol, Ann Arbor, MI 48109 USA.
[Moss, Joel] NHLBI, Cardiovasc & Pulm Branch, NIH, Bethesda, MD 20892 USA.
[Ntambi, James] Univ Wisconsin Madison, Dept Biochem, Madison, WI USA.
[Ntambi, James] Univ Wisconsin Madison, Dept Nutr Sci, Madison, WI USA.
[Pekala, Phillip] E Carolina Univ, Brody Sch Med, Dept Biochem & Mol Biol, Greenville, NC USA.
[Tang, Qi-Qun] Fudan Univ, Shanghai Med Coll, Dept Biochem & Mol Biol, Shanghai, Peoples R China.
[Wolfgang, Michael] Johns Hopkins Univ, Sch Med, Dept Biol Chem, Baltimore, MD 21205 USA.
[Bernlohr, David A.] Univ Minnesota, Dept Biochem Mol Biol & Biophys, Minneapolis, MN 55455 USA.
RP Bernlohr, DA (reprint author), Univ Minnesota, Dept Biochem Mol Biol & Biophys, Minneapolis, MN 55455 USA.
EM bernlohr@umn.edu
NR 1
TC 0
Z9 0
U1 0
U2 3
PU ELSEVIER SCIENCE LONDON
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 1043-2760
J9 TRENDS ENDOCRIN MET
JI Trends Endocrinol. Metab.
PD NOV
PY 2014
VL 25
IS 11
BP 609
EP 609
DI 10.1016/j.tem.2014.09.002
PG 1
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA AS8RB
UT WOS:000344514800008
ER
PT J
AU Gundisch, S
Slotta-Huspenina, J
Verderio, P
Ciniselli, CM
Pizzamiglio, S
Schott, C
Drecoll, E
Viertler, C
Zatloukal, K
Kap, M
Riegman, P
Esposito, I
Specht, K
Babaryka, G
Asslaber, M
Bodo, K
den Bakker, M
den Hollander, J
Fend, F
Neumann, J
Reu, S
Perren, A
Langer, R
Lugli, A
Becker, I
Richter, T
Kayser, G
May, AM
Carneiro, F
Lopes, JM
Sobin, L
Hofler, H
Becker, KF
AF Guendisch, Sibylle
Slotta-Huspenina, Julia
Verderio, Paolo
Ciniselli, Chiara Maura
Pizzamiglio, Sara
Schott, Christina
Drecoll, Enken
Viertler, Christian
Zatloukal, Kurt
Kap, Marcel
Riegman, Peter
Esposito, Irene
Specht, Katja
Babaryka, Gregor
Asslaber, Martin
Bodo, Koppany
den Bakker, Michael
den Hollander, Jan
Fend, Falko
Neumann, Jens
Reu, Simone
Perren, Aurel
Langer, Rupert
Lugli, Alessandro
Becker, Ingrid
Richter, Thomas
Kayser, Gian
May, Annette M.
Carneiro, Fatima
Lopes, Jose Manuel
Sobin, Leslie
Hoefler, Heinz
Becker, Karl-Friedrich
TI Evaluation of colon cancer histomorphology: a comparison between
formalin and PAXgene tissue fixation by an international ring trial
SO VIRCHOWS ARCHIV
LA English
DT Article
DE Histomorphology; Molecular diagnostic; Colon cancer; Tissue
preservation; Formalin free; Reproducibility
ID LYMPHOVASCULAR INVASION; BREAST-CANCER; OBSERVER AGREEMENT;
FORMALDEHYDE; MICROSCOPY; PATHOLOGY; COHORT
AB The aim of our study was to evaluate the quality of histo- and cytomorphological features of PAXgene-fixed specimens and their suitability for histomorphological classification in comparison to standard formalin fixation. Fifteen colon cancer tissues were collected, divided into two mirrored samples and either formalin fixed (FFPE) or PAXgene fixed (PFPE) before paraffin embedding. HE- and PAS-stained sections were scanned and evaluated in a blinded, randomised ring trial by 20 pathologists from Europe and the USA using virtual microscopy. The pathologists evaluated histological grading, histological subtype, presence of adenoma, presence of lymphovascular invasion, quality of histomorphology and quality of nuclear features. Statistical analysis revealed that the reproducibility with regard to grading between both fixation methods was rather satisfactory (weighted kappa statistic (k (w)) = 0.73 (95 % confidence interval (CI), 0.41-0.94)), with a higher agreement between the reference evaluation and the PFPE samples (k (w) = 0.86 (95 % CI, 0.67-1.00)). Independent from preservation method, inter-observer reproducibility was not completely satisfactory (k (w) = 0.60). Histomorphological quality parameters were scored equal or better for PFPE than for FFPE samples. For example, overall quality and nuclear features, especially the detection of mitosis, were judged significantly better for PFPE cases. By contrast, significant retraction artefacts were observed more frequently in PFPE samples. In conclusion, our findings suggest that the PAXgene Tissue System leads to excellent preservation of histomorphology and nuclear features of colon cancer tissue and allows routine morphological diagnosis.
C1 [Guendisch, Sibylle; Slotta-Huspenina, Julia; Schott, Christina; Drecoll, Enken; Esposito, Irene; Specht, Katja; Babaryka, Gregor; Hoefler, Heinz; Becker, Karl-Friedrich] Tech Univ Munich, Inst Pathol, D-81675 Munich, Germany.
[Verderio, Paolo; Ciniselli, Chiara Maura; Pizzamiglio, Sara] Fdn IRCCS, Ist Nazl Tumori, Unit Med Stat Biometry & Bioinformat, I-20133 Milan, Italy.
[Viertler, Christian; Zatloukal, Kurt; Asslaber, Martin; Bodo, Koppany] Med Univ Graz, Inst Pathol, A-8036 Graz, Austria.
[Kap, Marcel; Riegman, Peter; den Bakker, Michael; den Hollander, Jan] Erasmus MC, Dept Pathol, NL-3000 CA Rotterdam, Netherlands.
[Fend, Falko] Univ Tubingen, Inst Pathol, D-72076 Tubingen, Germany.
[Neumann, Jens; Reu, Simone] Univ Munich, Inst Pathol, D-80337 Munich, Germany.
[Perren, Aurel; Langer, Rupert; Lugli, Alessandro] Univ Bern, Inst Pathol, CH-3010 Bern, Switzerland.
[Becker, Ingrid; Richter, Thomas] Pathol Rosenheim, D-83022 Rosenheim, Germany.
[Kayser, Gian; May, Annette M.] Univ Med Ctr Freiburg, Dept Pathol, D-79106 Freiburg, Germany.
[Carneiro, Fatima; Lopes, Jose Manuel] Univ Porto, Inst Mol Pathol & Immunol, IPATIMUP, P-4200465 Oporto, Portugal.
[Sobin, Leslie] NCI, Frederick Natl Lab Canc Res, Canc Human Biobank, Rockville, MD 20852 USA.
[Guendisch, Sibylle; Verderio, Paolo; Ciniselli, Chiara Maura; Pizzamiglio, Sara; Schott, Christina; Viertler, Christian; Zatloukal, Kurt; Kap, Marcel; Riegman, Peter; Becker, Karl-Friedrich] SPIDIA Consortium, Hilden, Germany.
RP Becker, KF (reprint author), SPIDIA Consortium, Hilden, Germany.
EM kf.becker@lrz.tum.de
RI Carneiro, Fatima/J-6432-2013; Verderio, Paolo/B-5034-2017; Pizzamiglio,
Sara/C-1061-2017; Ciniselli, Chiara/C-4518-2017;
OI Carneiro, Fatima/0000-0002-1964-1006; Verderio,
Paolo/0000-0002-9231-1281; Pizzamiglio, Sara/0000-0002-7759-0550;
Ciniselli, Chiara/0000-0003-4488-885X; Becker,
Karl-Friedrich/0000-0002-6801-4498; Lopes, Jose
Manuel/0000-0001-8597-3474; Perren, Aurel/0000-0002-6819-6092
FU European Union [222916]
FX This work was performed within the European consortium Standardisation
and Improvement of Generic Pre-analytical Tools and Procedures for In
Vitro Diagnostics (SPIDIA; www.spidia.eu), which is funded by the
European Union within the Seventh Framework Programme (FP7/2007-2013)
under grant agreement no. 222916.
NR 27
TC 8
Z9 8
U1 0
U2 9
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0945-6317
EI 1432-2307
J9 VIRCHOWS ARCH
JI Virchows Arch.
PD NOV
PY 2014
VL 465
IS 5
BP 509
EP 519
DI 10.1007/s00428-014-1624-4
PG 11
WC Pathology
SC Pathology
GA AS6WD
UT WOS:000344399200003
PM 25085759
ER
PT J
AU Lu, XY
Martin, C
Bouchard, C
Kozak, CA
AF Lu, Xiaoyu
Martin, Carrie
Bouchard, Christelle
Kozak, Christine A.
TI Escape variants of the XPR1 gammaretrovirus receptor are rare due to
reliance on a splice donor site and a short hypervariable loop
SO VIROLOGY
LA English
DT Article
DE XPR1 gammaretrovirus receptor; Xenotropic/polytropic gammaretroviruses;
Retrovirus restriction genes; Retrovirus evolution; Retrovirus entry
ID MOUSE XENOTROPIC GAMMARETROVIRUSES; MURINE LEUKEMIA VIRUSES;
CELL-SURFACE RECEPTOR; MAMMALIAN-CELLS; HOST-RANGE; DETERMINANTS; GENES;
EVOLUTION; LYMPHOMAS; ENTRY
AB Entry determinants in the XPR1 receptor for the xenotropic/polytropic mouse leukemia viruses (XP-MLVs) lie in its third and fourth putative extracellular loops (ECLs). The critical ECL3 receptor determinant overlies a splice donor and is evolutionarily conserved in vertebrate XPR1 genes; 2 of the 3 rare replacement mutations at this site destroy this receptor determinant. The 13 residue ECL4 is hypervariable, and replacement mutations carrying an intact ECL3 site alter but do not abolish receptor activity, including replacement of the entire loop with that of a jellyfish (Cnidaria) XPR1. Because ECL4 deletions are found in all X-MLV-infected Mus subspecies, we deleted each ECL4 residue to determine if deletion-associated restriction is residue-specific or is effected by loop size. All deletions influence receptor function, although different deletions affect different XP-MLVs. Thus, receptor usage of a constrained splice site and a loop that tolerates mutations severely limits the likelihood of host escape mutations. Published by Elsevier Inc.
C1 [Lu, Xiaoyu; Martin, Carrie; Kozak, Christine A.] NIAID, Mol Microbiol Lab, Bethesda, MD 20892 USA.
[Bouchard, Christelle] Univ Florida, Whitney Lab Marine Biosci, St Augustine, FL 32136 USA.
RP Kozak, CA (reprint author), NIAID, NIH, LMM Bldg 4,Room 329,4 Ctr Dr MSC 0460, Bethesda, MD 20892 USA.
EM ckozak@niaid.nih.gov
OI Blanchard, Carrie/0000-0002-1236-4245
FU National Institute of Allergy and Infectious Diseases, NIH
FX This work was supported by the Intramural Research Program of the
National Institute of Allergy and Infectious Diseases, NIH. We thank
Alicia Buckler-White and Ronald Plishka for sequencing.
NR 23
TC 0
Z9 0
U1 0
U2 1
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0042-6822
J9 VIROLOGY
JI Virology
PD NOV
PY 2014
VL 468
BP 63
EP 71
DI 10.1016/j.virol.2014.07.049
PG 9
WC Virology
SC Virology
GA AS7KF
UT WOS:000344434400008
PM 25151060
ER
PT J
AU McCracken, MK
Christofferson, RC
Grasperge, BJ
Calvo, E
Chisenhall, DM
Mores, CN
AF McCracken, M. K.
Christofferson, R. C.
Grasperge, B. J.
Calvo, E.
Chisenhall, D. M.
Mores, C. N.
TI Aedes aegypti salivary protein "aegyptin" co-inoculation modulates
dengue virus infection in the vertebrate host
SO VIROLOGY
LA English
DT Article
DE Aegyptin; Allergen; Dengue; Mosquito; Mouse; Saliva; Virus
ID ADULT FEMALE MOSQUITO; T-CELLS; NONVASCULAR DELIVERY; IMMUNE-RESPONSE;
MICE; ALLERGY; GLANDS; SUSCEPTIBILITY; INTERLEUKIN-5; TRANSMISSION
AB Dengue virus (DENV) is transmitted in the saliva of the mosquito vector Aedes aegypti during blood meal acquisition. This saliva is composed of numerous proteins with the capacity to disrupt hemostasis or modulate the vertebrate immune response. One such protein, termed "aegyptin," is an allergen and inhibitor of clot formation, and has been found in decreased abundance in the saliva of DENV-infected mosquitoes. To examine the influence of aegyptin on DENV infection of the vertebrate, we inoculated IRF-3/7(-/- -/-) mice with DENV serotype 2 strain 1232 with and without co-inoculation of aegyptin. Mice that received aegyptin exhibited decreased DENV titers in inoculation sites and in circulation, as well as increased concentrations of GM-CSF, IFN-gamma, IL-5, and IL-6, at 48 h post-inoculation when compared to mice that received inoculation of DENV alone. These and other data suggest that aegyptin impacts DENV perpetuation via elevated induction of the immune response. (C) 2014 Elsevier Inc. All rights reserved.
C1 [McCracken, M. K.; Christofferson, R. C.; Grasperge, B. J.; Chisenhall, D. M.; Mores, C. N.] Louisiana State Univ, Sch Vet Med, Dept Pathobiol Sci, Baton Rouge, LA 70803 USA.
[Calvo, E.] NIH, Lab Malaria & Vector Res, Rockville, MD 20852 USA.
RP Mores, CN (reprint author), Louisiana State Univ, Sch Vet Med, Dept Pathobiol Sci, Skip Bertman Dr, Baton Rouge, LA 70803 USA.
EM cmores@lsu.edu
OI Grasperge, Britton/0000-0001-5592-9413; Calvo, Eric/0000-0001-7880-2730
FU National Institutes of Health [NIH/NIGMS 8P20GM103458, 5U01GM097661]
FX This work was supported by the National Institutes of Health Grants
NIH/NIGMS 8P20GM103458 and 5U01GM097661.
NR 55
TC 6
Z9 6
U1 4
U2 17
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0042-6822
J9 VIROLOGY
JI Virology
PD NOV
PY 2014
VL 468
BP 133
EP 139
DI 10.1016/j.virol.2014.07.019
PG 7
WC Virology
SC Virology
GA AS7KF
UT WOS:000344434400016
PM 25173089
ER
PT J
AU Glineur, SF
Bowen, AB
Percopo, CM
Garcia-Crespo, KE
Dyer, KD
Ochkur, SI
Lee, NA
Lee, JJ
Domachowske, JB
Rosenberg, HF
AF Glineur, Stephanie F.
Bowen, Aaron B.
Percopo, Caroline M.
Garcia-Crespo, Katia E.
Dyer, Kimberly D.
Ochkur, Sergei I.
Lee, Nancy A.
Lee, James J.
Domachowske, Joseph B.
Rosenberg, Helene F.
TI Sustained inflammation and differential expression of interferons type I
and III in PVM-infected interferon-gamma (IFN gamma) gene-deleted mice
SO VIROLOGY
LA English
DT Article
DE Inflammation; Pneumovirus; Interferon; Eosinophils
ID RESPIRATORY SYNCYTIAL VIRUS; LETHAL PNEUMOVIRUS INFECTION; PNEUMONIA
VIRUS; T-CELLS; HOST-RESISTANCE; BONE-MARROW; EX-VIVO; RECEPTOR; MOUSE;
EOSINOPHILS
AB Interferon gamma (IFN gamma) has complex immunomodulatory and antiviral properties. While IFN gamma is detected in the airways in response to infection with the pneumovirus pathogen, pneumonia virus of mice (PVM; Family Paramyxoviridae), its role in promoting disease has not been fully explored. Here, we evaluate PVM infection in IFN gamma(-/-) mice. Although the IFN gamma gene-deletion has no impact on weight loss, survival or virus kinetics, expression of IFN beta, IFN lambda 2/3 and IFN-stimulated 2-5' oligoadenylate synthetases was significantly diminished compared to wild-type counterparts. Furthermore, PVM infection in IFN gamma(-/-) mice promoted prominent inflammation, including eosinophil and neutrophil infiltration into the airways and lung parenchyma, observed several days after peak virus titer. Potential mechanisms include over-production of chemoattractant and eosinophil-active cytokines (CXCL1, CCL11, CCL3 and IL5) in PVM-infected IFN gamma(-/-) mice; likewise, IFN gamma actively antagonized IL5-dependent eosinophil survival ex vivo. Our results may have clinical implications for pneumovirus infection in individuals with IFN gamma signaling defects. Published by Elsevier Inc.
C1 [Glineur, Stephanie F.; Bowen, Aaron B.; Percopo, Caroline M.; Garcia-Crespo, Katia E.; Dyer, Kimberly D.; Rosenberg, Helene F.] NIAID, Inflammat Immunobiol Sect, NIH, Bethesda, MD 20892 USA.
[Ochkur, Sergei I.; Lee, Nancy A.; Lee, James J.] Mayo Clin Arizona, Dept Biochem & Mol Biol, Div Pulm Med, Scottsdale, AZ 85259 USA.
[Domachowske, Joseph B.] SUNY Upstate Med Univ, Dept Pediat, Syracuse, NY 13210 USA.
RP Rosenberg, HF (reprint author), NIAID, Inflammat Immunobiol Sect, Lab Allerg Dis, NIH, Bldg 10,Room 11C215,9000 Rockville Pike, Bethesda, MD 20892 USA.
FU NIAID Division of Intramural Research [AI000943]; Huynen Foundation
(University of Liege, Belgium); Rotary Foundation, Rotary International
FX Work supported by NIAID Division of Intramural Research funding
(AI000943 to HFR) the Huynen Foundation (University of Liege, Belgium)
and the Rotary Foundation, Rotary International (to SFG).
NR 70
TC 2
Z9 2
U1 0
U2 4
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0042-6822
J9 VIROLOGY
JI Virology
PD NOV
PY 2014
VL 468
BP 140
EP 149
DI 10.1016/j.virol.2014.07.039
PG 10
WC Virology
SC Virology
GA AS7KF
UT WOS:000344434400017
PM 25173090
ER
PT J
AU Ng, M
Ndungo, E
Jangra, RK
Cai, YY
Postnikova, E
Radoshitzky, SR
Dye, JM
de Arellano, ER
Negredo, A
Palacios, G
Kuhn, JH
Chandran, K
AF Ng, Melinda
Ndungo, Esther
Jangra, Rohit K.
Cai, Yingyun
Postnikova, Elena
Radoshitzky, Sheli R.
Dye, John M.
Ramirez de Arellano, Eva
Negredo, Ana
Palacios, Gustavo
Kuhn, Jens H.
Chandran, Kartik
TI Cell entry by a novel European filovirus requires host endosomal
cysteine proteases and Niemann-Pick C1
SO VIROLOGY
LA English
DT Article
DE Lloviu virus; Ebola; Filovirus; Viral entry; Viral membrane fusion;
Viral glycoprotein; Endosomal cysteine proteases; Viral receptor;
Niemann-Pick C1; NPC1; Cuevavirus; Filoviridae
ID EBOLA-VIRUS GLYCOPROTEIN; CURRENT KNOWLEDGE; MEMBRANE-FUSION; MARBURG
VIRUS; DELTA-PEPTIDE; RESTON-VIRUS; DC-SIGN; CHOLESTEROL; INFECTION;
RECEPTOR
AB Lloviu virus (LLOV), a phylogenetically divergent filovirus, is the proposed etiologic agent of die-offs of Schreibers's long-fingered bats (Miniopterus schreibersii) in western Europe. Studies of LLOV remain limited because the infectious agent has not yet been isolated. Here, we generated a recombinant vesicular stomatitis virus expressing the LLOV spike glycoprotein (GP) and used it to show that LLOV GP resembles other filovirus GP proteins in structure and function. LLOV GP must be cleaved by endosomal cysteine proteases during entry, but is much more protease-sensitive than EBOV GP. The EBOV/MARV receptor, Niemann Pick C1 (NPC1), is also required for LLOV entry, and its second luminal domain is recognized with high affinity by a cleaved form of LLOV GP, suggesting that receptor binding would not impose a barrier to LLOV infection of humans and non-human primates. The use of NPC1 as an intracellular entry receptor may be a universal property of filoviruses. (C) 2014 Elsevier Inc. All rights reserved.
C1 [Ng, Melinda; Ndungo, Esther; Jangra, Rohit K.; Chandran, Kartik] Albert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 10461 USA.
[Cai, Yingyun; Postnikova, Elena; Kuhn, Jens H.] NIAID, Integrated Res Facil Ft Detrick, NIH, Frederick, MD 21702 USA.
[Radoshitzky, Sheli R.; Dye, John M.; Palacios, Gustavo] United States Army Med Res Inst Infect Dis, Frederick, MD 21702 USA.
[Ramirez de Arellano, Eva; Negredo, Ana] Inst Salud Carlos III, Natl Ctr Microbiol, Madrid 28220, Spain.
RP Chandran, K (reprint author), Albert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 10461 USA.
EM kartik.chandran@einstein.yu.edu
RI Kuhn, Jens H./B-7615-2011; Palacios, Gustavo/I-7773-2015;
OI Kuhn, Jens H./0000-0002-7800-6045; Palacios,
Gustavo/0000-0001-5062-1938; chandran, kartik/0000-0003-0232-7077;
Ndungo, Esther/0000-0002-9975-7032
FU Albert Einstein College of Medicine; NIH [R01 AI088027]; Irma T.
Hirschl/Monique Weill-Caulier Trust; JSTO-CBD Defense Threat Reduction
Agency [CB3947]; RICET Network on Tropical Diseases-ISCIII; Sara Sorrel
program FIS-Spain; Defense Threat Reduction Agency [1881290]; NIAID
[HHSN272200700016I]
FX We thank Rohini G. Sandesara and Tyler Krause for excellent technical
support, and Jiro Wada (Integrated Research Facility at Fort Detrick)
for help with creating supplementary figures. We also thank Margaret C.
Kielian (Einstein) and Dan S. Ory (Washington University School of
Medicine) for their gift of the FD11 and M12 cell lines, respectively.
This work was supported by the Albert Einstein College of Medicine and
by NIH Grant R01 AI088027 (to K.C.). K.C. and R.K.J. were additionally
supported by a fellowship from the Irma T. Hirschl/Monique Weill-Caulier
Trust (to K.C.). J.M.D. was supported by JSTO-CBD Defense Threat
Reduction Agency project CB3947. A.N. was supported by a RICET Network
on Tropical Diseases-ISCIII. E.R.A. was supported by a Sara Sorrel
program FIS-Spain. G.P. was supported by Defense Threat Reduction Agency
Project 1881290. The content of this publication does not necessarily
reflect the views or policies of the US Department of the Army, the US
Department of Defense, or the US Department of Health and Human
Services, or of the institutions and companies affiliated with the
authors. YC, EP, and JHK performed this work as employees of Tunnell
Government Services, Inc., a subcontractor to Battelle Memorial
Institute, under Battelle's prime contract with NIAID, under Contract
no. HHSN272200700016I.
NR 70
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U1 2
U2 25
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0042-6822
J9 VIROLOGY
JI Virology
PD NOV
PY 2014
VL 468
BP 637
EP 646
DI 10.1016/j.virol.2014.08.019
PG 10
WC Virology
SC Virology
GA AS7KF
UT WOS:000344434400066
PM 25310500
ER
PT J
AU Bendtsen, P
Damsgaard, MT
Huckle, T
Casswell, S
Kuntsche, E
Arnold, P
de Looze, ME
Hofmann, F
Hublet, A
Simons-Morton, B
ter Bogt, T
Holstein, BE
AF Bendtsen, Pernille
Damsgaard, Mogens Trab
Huckle, Taisia
Casswell, Sally
Kuntsche, Emmanuel
Arnold, Petra
de Looze, Margreet E.
Hofmann, Felix
Hublet, Anne
Simons-Morton, Bruce
ter Bogt, Tom
Holstein, Bjorn E.
TI Adolescent alcohol use: a reflection of national drinking patterns and
policy?
SO ADDICTION
LA English
DT Article
DE Adolescents; alcohol control policies; alcohol use; country-level
predictors; cross-national studies; minimum purchasing age
ID GENDER-DIFFERENCES; HEAVY DRINKING; UNITED-STATES; CONSUMPTION; AGE;
COUNTRIES; DRUNKENNESS; BEHAVIOR; YOUTH; CONSEQUENCES
AB AimsTo analyse how adolescent drunkenness and frequency of drinking were associated with adult drinking patterns and alcohol control policies.
Design, Setting and ParticipantsCross-sectional survey data on 13- and 15-year-olds in 37 countries who participated in the Health Behaviour in School-Aged Children (HBSC) Study in 2010 (n=144788) were linked to national-level indicators on alcohol control policies and adult drinking patterns.
MeasurementsOutcome measures were self-reported weekly drinking and life-time drunkenness (drunk once or more). Data were analysed using multi-level logistic regression models.
FindingsIn the mutually adjusted models, adolescent drunkenness was associated significantly with high adult alcohol consumption [odds ratio (OR)=3.15 among boys, 95% confidence interval (CI)=2.13-4.64, OR girls=2.44, CI=1.57-3.80] and risky drinking patterns in the adult population (OR boys=2.02, CI=1.33-3.05, OR girls=1.61, CI=1.18-2.18). The level of abstainers in the adult population was also associated significantly with girls' drunkenness; a 10% increase in the number of abstainers in a country reduced the odds of drunkenness with 21% (OR=0.79, CI=0.68-0.90). Weekly drinking was associated significantly with weak restrictions on availability (OR boys=2.82, CI=1.74-4.54, OR girls=2.00, CI=1.15-3.46) and advertising (OR boys=1.56, CI=1.02-2.40, OR girls=1.79, CI=1.10-2.94).
ConclusionsComparing data cross-nationally, high levels of adult alcohol consumption and limited alcohol control policies are associated with high levels of alcohol use among adolescents.
C1 [Bendtsen, Pernille; Damsgaard, Mogens Trab; Holstein, Bjorn E.] Univ Southern Denmark, Natl Inst Publ Hlth, DK-1353 Copenhagen, Denmark.
[Huckle, Taisia; Casswell, Sally] Massey Univ, Sch Publ Hlth, SHORE & Whariki Res Ctr, Auckland, New Zealand.
[Kuntsche, Emmanuel] Swiss Inst Prevent Alcohol & Drug Problems SIPA, Res Dept, Lausanne, Switzerland.
[Kuntsche, Emmanuel] Radboud Univ Nijmegen, Inst Behav Sci, Nijmegen, Netherlands.
[Arnold, Petra] Natl Inst Child Hlth, Dept Res, Budapest, Hungary.
[de Looze, Margreet E.; ter Bogt, Tom] Univ Utrecht, Fac Social & Behav Sci, Dept Child & Adolescent Studies, Utrecht, Netherlands.
[Hofmann, Felix] Ludwig Boltzmann Inst Hlth Promot Res, Vienna, Austria.
[Hublet, Anne] Univ Ghent, Fac Med, Dept Publ Hlth, B-9000 Ghent, Belgium.
[Simons-Morton, Bruce] Div Epidemiol, Prevent Res Branch, Rockville, MD USA.
[Simons-Morton, Bruce] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Rockville, MD USA.
RP Bendtsen, P (reprint author), Univ Southern Denmark, Natl Inst Publ Hlth, DK-1353 Copenhagen, Denmark.
EM pebn@niph.dk
OI Holstein, Bjorn/0000-0002-4348-280X; Simons-Morton,
Bruce/0000-0003-1099-6617
FU Nordea Foundation [02-2011-0122]
FX HBSC is an international study carried out in collaboration with
WHO/EURO. We thank International Coordinator of the 2009/10 study
Professor Candace Currie, University of Edinburgh, Scotland and the data
bank manager, Professor Oddrun Samdal, University of Bergen, Norway. The
authors of this study thank all the schools and students who took part
in the HBSC surveys. We also thank all our international colleagues
mentioned in Table 1 for thorough sampling and data collection. A list
of the participating researchers can be found on the HBSC website
(http://www.hbsc.org). Data collection was funded separately by each of
the participating countries and regions. Production of this manuscript
was funded by the Nordea Foundation (grant number 02-2011-0122).
NR 56
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U1 4
U2 26
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 NOV
PY 2014
VL 109
IS 11
BP 1857
EP 1868
DI 10.1111/add.12681
PG 12
WC Substance Abuse; Psychiatry
SC Substance Abuse; Psychiatry
GA AR7JC
UT WOS:000343754500015
PM 25041190
ER
PT J
AU Reynolds, SJ
Sempa, JB
Kiragga, AN
Newell, K
Nakigozi, G
Galiwango, R
Gray, R
Quinn, TC
Serwadda, D
Chang, L
AF Reynolds, Steven J.
Sempa, Joseph B.
Kiragga, Agnes N.
Newell, Kevin
Nakigozi, Gertrude
Galiwango, Ronald
Gray, Ron
Quinn, Thomas C.
Serwadda, David
Chang, Larry
TI Is CD4 Monitoring Needed Among Ugandan Clients Achieving a Virologic and
Immunologic Response to Treatment?
SO AIDS PATIENT CARE AND STDS
LA English
DT Article
ID RECEIVING ANTIRETROVIRAL THERAPY; TREATMENT FAILURE; CRITERIA;
MORTALITY; INDIVIDUALS; SUPPRESSION; ADULTS
AB It is unclear whether ongoing CD4 monitoring is needed following immunologic and virologic response to antiretroviral therapy (ART). We investigated the proportion of clients who achieved a virologic and immunologic response and then had a subsequent CD4 count <200 cells/mu L despite continued virologic suppression. Included in this analysis were clients receiving ART through the Rakai Health Sciences Program between June 2004-May 2013 who achieved a CD4 >= 200 cells/mu L and VL <= 400 copies/mL and who had three sets of CD4 and VL measurements (defined as a sequence) within a 390 day period. A CD4 decline was defined as any drop in CD4 count to <200 cells/mu L during a period of viral suppression. A total of 1553 clients were included, 68% females, mean age of 35.5 years (SD 8.3), median baseline CD4 count 183 cells/mu L (IQR 106-224). 43 (2.8%) clients developed CD4 declines, the majority, 32/43 (74%), among individuals whose initial CD4 was <300 cells/mu L. Of the 43 clients with CD4 declines, 24 had an additional CD4 measurement and 20/24 (83%) achieved a CD4 >= 200 cell/mu L on their next measurement (median 285 cells/mu L; IQR 220-365). CD4 declines were significantly greater among those with lower CD4 at sequence initiation [adjusted hazard ratio (AHR) 4.3 (95% CI 2.1, 9.0) CD4 200-249 versus >= 350 cells/mu L]. Clients who achieved an immunologic and virologic response to ART were unlikely to experience a subsequent CD4 count decline to <200 cells/mu L, and among those experiencing a decline, the majority were transient in nature. Thus, ongoing CD4 monitoring could be omitted.
C1 [Reynolds, Steven J.; Quinn, Thomas C.] NIAID, Div Intramural Res, NIH, Bethesda, MD 20892 USA.
[Reynolds, Steven J.; Quinn, Thomas C.; Chang, Larry] Johns Hopkins Univ, Sch Med, Baltimore, MD USA.
[Sempa, Joseph B.; Kiragga, Agnes N.] Makerere Univ, Coll Hlth Sci, Infect Dis Inst, Kampala, Uganda.
[Newell, Kevin] Leidos Biomed Res Inc, Clin Res Directorate CMRP, Frederick Natl Lab Canc Res, Frederick, MD USA.
[Nakigozi, Gertrude; Galiwango, Ronald; Serwadda, David] Rakai Hlth Sci Program, Kalisizo, Uganda.
[Gray, Ron; Chang, Larry] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA.
[Serwadda, David] Makerere Univ, Sch Publ Hlth, Kampala, Uganda.
RP Reynolds, SJ (reprint author), US Embassy, POB 7007,Plot 1577 Gaba Rd, Kampala, Uganda.
EM sjr@jhmi.edu
FU Division of Intramural Research, National Institute of Allergy and
Infectious Diseases, National Institutes of Health; National Institute
of Mental Health of the National Institutes of Health [K23MH086338];
National Cancer Institute, National Institutes of Health
[HHSN261200800001E]
FX This project was funded in part by the Division of Intramural Research,
National Institute of Allergy and Infectious Diseases, National
Institutes of Health, and in part by the National Institute of Mental
Health of the National Institutes of Health (K23MH086338). 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 United States Government.
NR 17
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U1 0
U2 1
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1087-2914
EI 1557-7449
J9 AIDS PATIENT CARE ST
JI Aids Patient Care STDS
PD NOV 1
PY 2014
VL 28
IS 11
BP 575
EP 578
DI 10.1089/apc.2014.0086
PG 4
WC Public, Environmental & Occupational Health; Infectious Diseases
SC Public, Environmental & Occupational Health; Infectious Diseases
GA AS0QM
UT WOS:000343982600003
PM 25290988
ER
PT J
AU Leyva, B
Allen, JD
Tom, LS
Ospino, H
Torres, MI
Abraido-Lanza, AF
AF Leyva, Bryan
Allen, Jennifer D.
Tom, Laura S.
Ospino, Hosffman
Torres, Maria Idali
Abraido-Lanza, Ana F.
TI Religion, Fatalism, and Cancer Control: A Qualitative Study among
Hispanic Catholics
SO AMERICAN JOURNAL OF HEALTH BEHAVIOR
LA English
DT Article
DE fatalism; cancer fatalism; religion; Catholic; Latinos; Hispanics;
cancer; cancer screening
ID MEXICAN-AMERICAN WOMEN; BREAST-CANCER; CERVICAL-CANCER;
AFRICAN-AMERICAN; HEALTH BEHAVIORS; PROSTATE-CANCER; SCREENING
BEHAVIORS; EXPLANATORY MODELS; UNITED-STATES; BELIEFS
AB Objectives: To assess cancer perceptions among churchgoers and to examine the potential influence of fatalism and religious beliefs on the use of cancer screening tests. Methods: Eight semi-structured focus groups were conducted among 67 Hispanic Catholics in Massachusetts. Results: In this sample, there were few references to fatalistic beliefs about cancer and nearly universal endorsement of the utility of cancer screening for cancer early detection. Most participants reported that their religious beliefs encouraged them to use health services, including cancer-screening tests. Although participants agreed that God plays an active role in health, they also affirmed the importance of self-agency in determining cancer outcomes. Conclusions: Our findings challenge the assumption that fatalism is an overriding perspective among Hispanics. Catholic religious beliefs may contribute to positive health attitudes and behaviors.
C1 [Leyva, Bryan] NCI, NIH, Bethesda, MD 20892 USA.
[Allen, Jennifer D.] Tufts Univ, Boston, MA 02111 USA.
[Tom, Laura S.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Ospino, Hosffman] Boston Coll, Sch Theol & Minist, Chestnut Hill, MA 02167 USA.
[Torres, Maria Idali] Univ Massachusetts, Dept Anthropol, Boston, MA 02125 USA.
[Abraido-Lanza, Ana F.] Columbias Mailman Sch Publ Hlth, New York, NY USA.
RP Leyva, B (reprint author), NCI, NIH, Bethesda, MD 20892 USA.
EM leyvabryan@gmail.com
RI Allen, Jennifer/M-2113-2015
FU NCATS NIH HHS [UL1TR000040, UL1 TR000040]; NCCDPHP CDC HHS [U48DP001946,
U48 DP001946]; NCI NIH HHS [U54CA156732, U54 CA156732]; NIGMS NIH HHS
[R25 GM062454, R25GM062454]
NR 85
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U1 3
U2 13
PU PNG PUBLICATIONS
PI OAK RIDGE
PA 2205-K OAK RIDGE RD, #115, OAK RIDGE, NC 27310 USA
SN 1945-7359
J9 AM J HEALTH BEHAV
JI Am. J. Health Behav.
PD NOV
PY 2014
VL 38
IS 6
BP 839
EP 849
DI 10.5993/AJHB.38.6.6
PG 11
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA AS1JE
UT WOS:000344036600006
PM 25207510
ER
PT J
AU Rezende, FA
Lapalme, E
Qian, CX
Smith, LE
Sangiovanni, JP
Sapieha, P
AF Rezende, Flavio A.
Lapalme, Eric
Qian, Cynthia X.
Smith, Lois E.
Sangiovanni, John Paul
Sapieha, Przemyslaw
TI Omega-3 Supplementation Combined With Anti-Vascular Endothelial Growth
Factor Lowers Vitreal Levels of Vascular Endothelial Growth Factor in
Wet Age-Related Macular Degeneration
SO AMERICAN JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID POLYUNSATURATED FATTY-ACIDS; DOCOSAHEXAENOIC ACID; UNITED-STATES;
PLASMA-LEVELS; DISEASE; ANGIOGENESIS; RANIBIZUMAB; METAANALYSIS;
BEVACIZUMAB; BURDEN
AB PURPOSE: To determine the influence of omega-3 supplementation on vitreous vascular endothelial growth factor A (VEGF-A) levels in patients with exudative age-related macular degeneration (wet AMD) receiving intravitreal anti-VEGF treatment.
DESIGN: Prospective, randomized, open-label, single-center, clinical trial, consecutive interventional case series.
METHODS: The study included 3 cohorts with wet AMD and a control group with epiretinal membrane or macular hole. Twenty wet AMD patients being treated with anti-VEGF were randomized to daily supplementation of antioxidants, zinc, and carotenoids with omega-3 fatty acids (docosahexaenoic acid and eicosapentaenoic acid; group 1, n = 10) or without omega-3 fatty acids (group 2, n = 10). They were compared with an anti-VEGF treatment-nave wet AMD group (group 3, n = 10) and an epiretinal membrane or macular hole group (group 4, n = 10). Primary outcome was vitreal VEGF-A levels (at the time of anti-VEGF injection). Secondary outcomes were plasma VEGF-A and central foveal thickness. Patients with new submacular hemorrhage or any other treatment within 3 months were excluded. Final analyses included 9, 6, 7, and 8 patients in groups 1 through 4, respectively.
RESULTS: Patients receiving omega-3s (group 1) had significantly lower levels of vitreal VEGF-A (141.11 +/- 61.89 pg/mL) when compared with group 2 (626.09 +/- 279.27 pg/mL; P = .036) and group 3 (735.48 +/- 216.43 pg/mL; P = .013), but similar levels to group 4(235.81 +/- 33.99 pg/mL; P = .215). All groups showed similar values for plasma VEGF-A and central foveal thickness measurements.
CONCLUSIONS: This study demonstrated that omega-3 supplementation combined with anti-VEGF treatment is associated with decreased vitreal VEGF-A levels in wet AMD patients. (C) 2014 The Authors. Published by Elsevier Inc. All rights reserved. This is an open access article under the CC BY-NC-SA license (http://creativecommons.or/licenses/by-nc-sa/3.0/).)
C1 [Rezende, Flavio A.; Lapalme, Eric; Qian, Cynthia X.; Sapieha, Przemyslaw] Univ Montreal, Maisonneuve Rosemont Hosp, Res Ctr, Dept Ophthalmol, Montreal, PQ, Canada.
[Smith, Lois E.] Harvard Univ, Sch Med, Dept Ophthalmol, Childrens Hosp Boston, Boston, MA USA.
[Sangiovanni, John Paul] NEI, Clin Trials Branch, NIH, Bethesda, MD 20892 USA.
RP Rezende, FA (reprint author), Maisonneuve Rosemont Hosp, Dept Ophthalmol, 5415 Blvd Assompt, Montreal, PQ H1T 2M4, Canada.
EM frezendef@hotmail.com
FU Novartis; Lachine, Quebec, Canada; Alcon Canada; Bausch &. Lomb,
Montreal, Quebec, Canada; Allergan, Markham, Ontario, Canada; Bayer,
Toronto, Ontario, Canada; Gerson Lehman Group; Department of
Ophthalmology, University of Montreal; Department of Ophthalmology,
Maisonneuve-Rosemont Hospital; Fond de Recherche en Ophtalmologie,
University of Montreal; Foundation Fighting Blindness Canada; Canadian
Institutes of Health Research [324573]; Retina Foundation of Canada;
Insight Instruments, Stuart, Florida, USA; Synergetics, Inc.; O'Fallon,
Missouri, USA; Novartis Canada, Montreal, Quebec, Canada; National
Institutes of Health, Bethesda, Maryland [EY022275, EY017017, P01
HD18655]; Research to Prevent Blindness, New York, New York, USA; Lowy
Medical Foundation; European Commission (LEHS) [305485]
FX ALL AUTHORS HAVE COMPLETED AND SUBMITTED THE ICMJE FORM FOR DISCLOSURE
OF POTENTIAL CONFLICTS OF INTEREST and the following were reported. Dr
Rezende has received consultation fees from Novartis, Lachine, Quebec,
Canada, Alcon Canada, Bausch &. Lomb, Montreal, Quebec, Canada,
Allergan, Markham, Ontario, Canada, and Bayer, Toronto, Ontario, Canada,
none of which are related to the current study. Przemyslaw Sapieha holds
a Canada Research Chair and has received consultation fees from Gerson
Lehman Group not related to the current research. Supported by the
Department of Ophthalmology, University of Montreal; Department of
Ophthalmology, Maisonneuve-Rosemont Hospital; Fond de Recherche en
Ophtalmologie, University of Montreal; Foundation Fighting Blindness
Canada; Grant 324573 from the Canadian Institutes of Health Research;
Retina Foundation of Canada; Insight Instruments, Stuart, Florida, USA;
Synergetics, Inc., O'Fallon, Missouri, USA; Novartis Canada, Montreal,
Quebec, Canada; Grants EY022275, EY017017, and P01 HD18655 from the
National Institutes of Health, Bethesda, Maryland; a Senior Investigator
Award from Research to Prevent Blindness, New York, New York, USA; the
Lowy Medical Foundation; and FP7 project 305485 of the European
Commission (LEHS). The sponsors or funding organizations had no role in
the design or conduct of this research. Involved in Design and conduct
of study (F.A.R., P.S.); Collection of data (F.A.R., E.L., C.X.Q.);
Management of data (F.A.R., E.L., P.S.); Analysis and interpretation of
data (F.A.R., E.L., L.S., J.P.S., P.S.); Preparation of manuscript
(F.A.R., E.L., P.S.); and Review and approval of manuscript (F.A.R.,
L.S., J.P.S., P.S.). The authors thank Karsten Gronert, School of
Optometry, University of California, Berkeley, California, USA, for
carrying out lipidomic assay on patient vitreous (data was not
included).
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U2 5
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9394
EI 1879-1891
J9 AM J OPHTHALMOL
JI Am. J. Ophthalmol.
PD NOV
PY 2014
VL 158
IS 5
BP 1071
EP 1078
DI 10.1016/j.ajo.2014.07.036
PG 8
WC Ophthalmology
SC Ophthalmology
GA AR7TT
UT WOS:000343783400028
PM 25089351
ER
PT J
AU Hingle, MD
Snyder, AL
McKenzie, NE
Thomson, CA
Logan, RA
Ellison, EA
Koch, SM
Harris, RB
AF Hingle, Melanie D.
Snyder, Aimee L.
McKenzie, Naja E.
Thomson, Cynthia A.
Logan, Robert A.
Ellison, Eden A.
Koch, Stephanie M.
Harris, Robin B.
TI Effects of a Short Messaging Service-Based Skin Cancer Prevention
Campaign in Adolescents
SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE
LA English
DT Article
ID RANDOMIZED CONTROLLED-TRIAL; SUN-PROTECTION BEHAVIORS; YOUNG-PEOPLE;
INTERVENTION; PREVALENCE; HEALTH; TEXT; QUESTIONNAIRE; SUNSCREEN;
EXPOSURE
AB Background: Skin cancer prevention emphasizes early adoption and practice of sun protection behaviors. Adolescence represents a high-risk period for ultraviolet radiation exposure, presenting an opportunity for intervention. The ubiquity of mobile phones among teens offers an engaging medium through which to communicate prevention messages.
Purpose: To evaluate a skin cancer prevention intervention using short messaging service (SMS, or text messages) to impact sun-related knowledge, beliefs, and behaviors among adolescents.
Methods: The intervention was conducted in middle school youth (N=113) recruited in April or October 2012. Participants were English speakers, 11-14 years old, routinely carried a mobile phone, and completed a 55-minute sun safety education program. Participants were sent three sun safety-themed SMS messages each week for 12 weeks. Skin and sun protective knowledge, beliefs, behaviors, and post-intervention program satisfaction were collected and analyzed at baseline and end of intervention (April/June 2012; October 2012/January 2013). Paired responses were tested for equality using Wilcoxon signed-rank tests.
Results: Ninety-six students (85%) completed the study. At 12 weeks, significant positive changes were reported for sun avoidance during peak ultraviolet radiation, sunscreen application, wearing hats and sunglasses, and knowledge about skin cancer risk. Participants expressed moderately high satisfaction with the program, and 15% shared messages with family or friends.
Conclusions: A brief, SMS-based intervention affected youth skin cancer prevention behaviors and knowledge. Future research will determine whether program effects were sustained at 24 weeks and explore how sun safety parenting practices inform these effects. (C) 2014 American Journal of Preventive Medicine. All rights reserved.
C1 [Hingle, Melanie D.] Univ Arizona, Dept Nutr Sci, Coll Agr & Life Sci, Tucson, AZ 85721 USA.
[Snyder, Aimee L.; Thomson, Cynthia A.; Koch, Stephanie M.; Harris, Robin B.] Univ Arizona, Mel & Enid Zuckerman Coll Publ Hlth, Tucson, AZ 85721 USA.
[McKenzie, Naja E.; Thomson, Cynthia A.; Koch, Stephanie M.; Harris, Robin B.] Univ Arizona, Skin Canc Inst, Tucson, AZ 85721 USA.
[McKenzie, Naja E.; Thomson, Cynthia A.; Koch, Stephanie M.; Harris, Robin B.] Univ Arizona, Ctr Canc, Tucson, AZ 85721 USA.
[Logan, Robert A.] Natl Lib Med, Bethesda, MD USA.
[Ellison, Eden A.] Marquette Univ, Coll Nursing, Milwaukee, WI 53233 USA.
RP Hingle, MD (reprint author), Univ Arizona, Dept Nutr Sci, Coll Agr & Life Sci, 1177 East 4th St, Tucson, AZ 85721 USA.
EM hinglem@u.arizona.edu
RI Emchi, Karma/Q-1952-2016
FU National Library of Medicine (NLM), NIH
FX This project is supported by a contract from the National Library of
Medicine (NLM), NIH. The NLM was consulted but did not manage the study
design, collection, analysis, or interpretation of data, writing of the
report, or the decision to submit the manuscript for publication. The
authors would like to acknowledge Nirav Merchant and David Parizek at
Arizona Research Laboratories at the University of Arizona for their
contributions to the software infrastructure and the mobile application
used in this study, and Jianhua Hilgaertner for her assistance with data
analysis. In addition, the authors would like to thank the teachers at
Emily Gray Junior High School, St. Gregory College Preparatory School,
and Desert Sky Middle School in Tucson AZ for their help in recruiting
youth to this study. Finally, the authors would like to acknowledge Lisa
Quale at the Skin Cancer Institute at the University of Arizona Cancer
Center, who helped in the development of skin cancer and sun safety
messages used for this study.
NR 38
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U1 2
U2 14
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0749-3797
EI 1873-2607
J9 AM J PREV MED
JI Am. J. Prev. Med.
PD NOV
PY 2014
VL 47
IS 5
BP 617
EP 623
DI 10.1016/j.amepre.2014.06.014
PG 7
WC Public, Environmental & Occupational Health; Medicine, General &
Internal
SC Public, Environmental & Occupational Health; General & Internal Medicine
GA AR6DP
UT WOS:000343673800010
PM 25053602
ER
PT J
AU Kepka, D
Breen, N
King, JB
Meissner, HI
Roland, KB
Benard, VB
Saraiya, M
AF Kepka, Deanna
Breen, Nancy
King, Jessica B.
Meissner, Helen I.
Roland, Katherine B.
Benard, Vicki B.
Saraiya, Mona
TI Demographic Factors Associated with Overuse of Pap Testing
SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE
LA English
DT Article
ID CERVICAL-CANCER; UNITED-STATES; OLDER WOMEN; PREVENTION; GUIDELINES
AB Background: Since 2003, U.S. Preventive Services Task Force guidelines recommend against Pap testing for women without a cervix following a hysterectomy and those aged >65 years. Few population-based studies have investigated factors associated with overuse of Pap testing in the U.S.
Purpose: To evaluate patient characteristics associated with overuse of Pap testing.
Methods: A cross-sectional study was conducted using data from the 2010 National Health Interview Survey (NHIS) for women aged >= 30 years. NHIS is a nationally representative survey that employs a random, stratified, multi-stage cluster sampling design. In 2010, the NHIS administered a Cancer Control Supplement with questions on cervical cancer screening and hysterectomy status. Conducted in 2011-2013, all analyses account for the stratification and clustering of data within the complex NHIS survey design. Multivariate logistic regression models were used in all analyses.
Results: Among women who have undergone a hysterectomy, younger age, Hispanic and black race/ethnicity, exceeding 400% of poverty level, and private health insurance coverage were significantly associated with receipt of a recent Pap test since hysterectomy. Among women aged >65 years, non-Hispanic white ethnicity, higher education level, exceeding 400% of poverty level, and no hysterectomy were significantly associated with receipt of a recent Pap test.
Conclusions: Targeted efforts to reduce unnecessary testing among older women and women with a hysterectomy in compliance with clinical recommendations for cervical cancer prevention are needed. Specific attention should be paid to privately insured women with incomes above 400% of the federal poverty level. (C) 2014 American Journal of Preventive Medicine. All rights reserved.
C1 [Kepka, Deanna] Univ Utah, Coll Nursing, Salt Lake City, UT 84112 USA.
[Kepka, Deanna; Breen, Nancy] NIH, NCI, Hlth Serv & Econ Branch, Rockville, MD USA.
[Meissner, Helen I.] NIH, Tobacco Regulatory Sci Program, Off Dis Prevent, Bethesda, MD 20892 USA.
[King, Jessica B.] CDC, Canc Surveillance Branch, Atlanta, GA 30333 USA.
[Roland, Katherine B.; Benard, Vicki B.; Saraiya, Mona] CDC, Natl Ctr Chron Dis Prevent & Hlth Promot, Div Canc Prevent & Control, Epidemiol & Appl Res Branch, Atlanta, GA 30333 USA.
RP Kepka, D (reprint author), Univ Utah, Coll Nursing, Huntsman Canc Inst, 2000 Circle Hope,Room 4144, Salt Lake City, UT 84112 USA.
EM deanna.kepka@hci.utah.edu
FU University of Utah College of Nursing; Huntsman Cancer Institute
Foundation; National Center for Advancing Translational Sciences of the
National Institutes of Health [1ULTR001067]
FX This research was supported by the University of Utah College of
Nursing, Huntsman Cancer Institute Foundation, and National Center for
Advancing Translational Sciences of the National Institutes of Health
(Award No. 1ULTR001067).
NR 17
TC 3
Z9 3
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0749-3797
EI 1873-2607
J9 AM J PREV MED
JI Am. J. Prev. Med.
PD NOV
PY 2014
VL 47
IS 5
BP 629
EP 633
DI 10.1016/j.amepre.2014.07.034
PG 5
WC Public, Environmental & Occupational Health; Medicine, General &
Internal
SC Public, Environmental & Occupational Health; General & Internal Medicine
GA AR6DP
UT WOS:000343673800012
PM 25175763
ER
PT J
AU Tanaka, N
Takahashi, S
Fang, ZZ
Matsubara, T
Krausz, KW
Qu, AJ
Gonzalez, FJ
AF Tanaka, Naoki
Takahashi, Shogo
Fang, Zhong-Ze
Matsubara, Tsutomu
Krausz, Kristopher W.
Qu, Aijuan
Gonzalez, Frank J.
TI Role of white adipose lipolysis in the development of NASH induced by
methionine- and choline-deficient diet
SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS
LA English
DT Article
DE Fasting response; Linoleic acid; Lipolysis; Metabolomics; Oleic acid;
Choline deficiency
ID FATTY LIVER-DISEASE; GROWTH-FACTOR 21; NONALCOHOLIC STEATOHEPATITIS;
ACID; MICE; TRIGLYCERIDE; METABOLOMICS; INFLAMMATION; LIPASE
AB Methionine- and choline-deficient diet (MCD) is a model for nonalcoholic steatohepatitis (NASH) in rodents. However, the mechanism of NASH development by dietary methionine/choline deficiency remains undetermined. To elucidate the early metabolic changes associated with MCD-NASH, serum metabolomic analysis was performed using mice treated with MCD and control diet for 3 days and 1 week, revealing significant increases in oleic and linoleic acids after MCD treatment. These increases were correlated with reduced body weight and white adipose tissue (WAT) mass, increased phosphorylation of hormone-sensitive lipase, and up-regulation of genes encoding carboxylesterase 3 and beta 2-adrenergic receptor in WAT, indicating accelerated lipolysis in adipocytes. The changes in serum fatty acids and WAT by MCD treatment were reversed by methionine supplementation, and similar alterations were detected in mice fed a methionine-deficient diet (MD), thus demonstrating that dietary methionine deficiency enhances lipolysis in WAT. MD treatment decreased glucose and increased fibroblast growth factor 21 in serum, thus exhibiting a similar metabolic phenotype as the fasting response. Comparison between MCD and choline-deficient diet (CD) treatments suggested that the addition of MD-induced metabolic alterations, such as WAT lipolysis, to CD-induced hepatic steatosis promotes liver injury. Collectively, these results demonstrate an important role for dietary methionine deficiency and WAT lipolysis in the development of MCD-NASH. Published by Elsevier B.V.
C1 [Tanaka, Naoki; Takahashi, Shogo; Fang, Zhong-Ze; Matsubara, Tsutomu; Krausz, Kristopher W.; Qu, Aijuan; Gonzalez, Frank J.] NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Fang, Zhong-Ze] Tianjin Med Univ, Sch Publ Hlth, Dept Toxicol, Tianjin, Peoples R China.
[Matsubara, Tsutomu] Osaka City Univ, Dept Anat & Regenerat Biol, Osaka 558, Japan.
RP Gonzalez, FJ (reprint author), NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM gonzalef@mail.nih.gov
FU Intramural Research Program, Center for Cancer Research, National Cancer
Institute, National Institutes of Health [U554 ES16015, 1R01ES022186-01]
FX We thank Linda G. Byrd and John Buckley for providing technical
assistance with the mouse studies. This study was supported by the
Intramural Research Program, Center for Cancer Research, National Cancer
Institute, U554 ES16015 and 1R01ES022186-01, National Institutes of
Health.
NR 37
TC 17
Z9 17
U1 0
U2 17
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1388-1981
EI 0006-3002
J9 BBA-MOL CELL BIOL L
JI Biochim. Biophys. Acta Mol. Cell Biol. Lipids
PD NOV
PY 2014
VL 1841
IS 11
BP 1596
EP 1607
DI 10.1016/j.bbalip.2014.08.015
PG 12
WC Biochemistry & Molecular Biology; Biophysics; Cell Biology
SC Biochemistry & Molecular Biology; Biophysics; Cell Biology
GA AR8XI
UT WOS:000343854300004
PM 25178843
ER
PT J
AU Logan, JK
Rais-Bahrami, S
Turkbey, B
Gomella, A
Amalou, H
Choyke, PL
Wood, BJ
Pinto, PA
AF Logan, Jennifer K.
Rais-Bahrami, Soroush
Turkbey, Baris
Gomella, Andrew
Amalou, Hayet
Choyke, Peter L.
Wood, Bradford J.
Pinto, Peter A.
TI Current status of magnetic resonance imaging (MRI) and ultrasonography
fusion software platforms for guidance of prostate biopsies
SO BJU INTERNATIONAL
LA English
DT Review
DE prostate MRI; MRI; US fusion; targeted biopsy; MRI; US fusion platforms
ID TRANSRECTAL ULTRASOUND GUIDANCE; RECTAL CORE BIOPSIES; CANCER-DETECTION;
MULTIPARAMETRIC MRI; TARGETED BIOPSY; DIAGNOSIS; IMPROVES; DISEASE;
ANTIGEN; SYSTEM
AB Prostate MRI is currently the best diagnostic imaging method for detecting PCa. Magnetic resonance imaging (MRI)/ultrasonography (US) fusion allows the sensitivity and specificity of MRI to be combined with the real-time capabilities of transrectal ultrasonography (TRUS). Multiple approaches and techniques exist for MRI/US fusion and include direct in bore' MRI biopsies, cognitive fusion, and MRI/US fusion via software-based image coregistration platforms.
C1 [Logan, Jennifer K.; Rais-Bahrami, Soroush; Pinto, Peter A.] NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA.
[Turkbey, Baris; Choyke, Peter L.] NCI, Mol Imaging Program, NIH, Bethesda, MD 20892 USA.
[Amalou, Hayet; Wood, Bradford J.; Pinto, Peter A.] NCI, Ctr Intervent Oncol, NIH, Bethesda, MD 20892 USA.
[Gomella, Andrew] NHLBI, Imaging Phys Lab, NIH, Bethesda, MD 20892 USA.
RP Pinto, PA (reprint author), NCI, Urol Oncol Branch, NIH, 10 Ctr Dr,MSC 1210,Bldg 10,CRC Room 2W-5940, Bethesda, MD 20892 USA.
EM pintop@mail.nih.gov
OI Rais-Bahrami, Soroush/0000-0001-9466-9925
FU NIH; National Cancer Institute; Center for Cancer Research; Center for
Interventional Oncology; Pfizer Inc; Doris Duke Charitable Foundation;
Alexandria Real Estate Equities, Inc.; Howard Hughes Medical Institute
FX This research was supported by the Intramural Research Program of the
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 (NIH) Medical Research
Scholars Program, a public-private partnership supported jointly by the
NIH and generous contributions to the Foundation for the NIH from Pfizer
Inc, The 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.
NR 49
TC 32
Z9 32
U1 2
U2 14
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1464-4096
EI 1464-410X
J9 BJU INT
JI BJU Int.
PD NOV
PY 2014
VL 114
IS 5
BP 641
EP 652
DI 10.1111/bju.12593
PG 12
WC Urology & Nephrology
SC Urology & Nephrology
GA AS4NY
UT WOS:000344254100008
PM 24298917
ER
PT J
AU Muller, BG
van den Bos, W
Brausi, M
Cornud, F
Gontero, P
Kirkham, A
Pinto, PA
Polascik, TJ
Rastinehad, AR
de Reijke, TM
de la Rosette, JJ
Ukimura, O
Villers, A
Walz, J
Wijkstra, H
Marberger, M
AF Muller, Berrend G.
van den Bos, Willemien
Brausi, Maurizio
Cornud, Francois
Gontero, Paolo
Kirkham, Alexander
Pinto, Peter A.
Polascik, Thomas J.
Rastinehad, Ardeshir R.
de Reijke, Theo M.
de la Rosette, Jean J.
Ukimura, Osamu
Villers, Arnauld
Walz, Jochen
Wijkstra, Hessel
Marberger, Michael
TI Role of multiparametric magnetic resonance imaging (MRI) in focal
therapy for prostate cancer: a Delphi consensus project
SO BJU INTERNATIONAL
LA English
DT Article
DE prostate cancer; focal therapy; multiparametric MRI; consensus
ID ABLATION; BIOPSY; TIME
AB ObjectiveTo define the role of multiparametric MRI (mpMRI) for treatment planning, guidance and follow-up in focal therapy for prostate cancer based on a multidisciplinary Delphi consensus project.
Materials and MethodsAn online consensus process based on a questionnaire was circulated according to the Delphi method. Discussion points were identified by literature research and were sent to the panel via an online questionnaire in three rounds. A face-to-face consensus meeting followed the three rounds of questions that were sent to a 48-participant expert panel consisting of urologists, radiologists and engineers. Participants were presented with the results of the previous rounds. Conclusions formulated from the results of the questionnaire were discussed in the final face-to-face meeting.
ResultsConsensus was reached in 41% of all key items. Patients selected for focal therapy should have biopsy-proven prostate cancer. Biopsies should ideally be performed after mpMRI of the prostate. Standardization of imaging protocols is essential and mpMRIs should be read by an experienced radiologist. In the follow-up after focal therapy, mpMRI should be performed after 6 months, followed by a yearly mpMRI. mpMRI findings should be confirmed by targeted biopsies before re-treatment. No consensus was reached on whether mpMRI could replace transperineal template saturation biopsies to exclude significant lesions outside the target lesion.
ConclusionsConsensus was reached on a number of areas related to the conduct, interpretation and reporting of mpMRI for use in treatment planning, guidance and follow-up of focal therapy for prostate cancer. Future studies, comparing mpMRI with transperineal saturation mapping biopsies, will confirm the importance of mpMRI for a variety of purposes in focal therapy for prostate cancer.
C1 [Muller, Berrend G.; van den Bos, Willemien; de Reijke, Theo M.; de la Rosette, Jean J.; Wijkstra, Hessel] AMC Univ Hosp, Dept Urol, Amsterdam, Netherlands.
[Brausi, Maurizio] EstenseS Agostino Hosp, Dept Urol, Modena, Italy.
[Cornud, Francois] Cochin Hosp, Dept Radiol, Paris, France.
[Gontero, Paolo] Molinette Univ Hosp, Dept Urol, Turin, Italy.
[Kirkham, Alexander] Univ Coll London Hosp, Dept Radiol, London, England.
[Pinto, Peter A.] NCI, Dept Urol, Bethesda, MD 20892 USA.
[Polascik, Thomas J.] Duke Univ, Med Ctr, Dept Surg Urol, Durham, NC USA.
[Rastinehad, Ardeshir R.] Smith Inst Urol, Dept Urol Radiol, New York, NY USA.
[Ukimura, Osamu] Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Dept Urol, Los Angeles, CA 90033 USA.
[Villers, Arnauld] CHU Lille, Dept Urol, F-59037 Lille, France.
[Walz, Jochen] Inst Paoli Calmettes Canc Ctr, Dept Urol, Marseille, France.
[Wijkstra, Hessel] Eindhoven Univ Technol, Dept Elect Engn, NL-5600 MB Eindhoven, Netherlands.
[Marberger, Michael] Med Univ Vienna, Dept Urol, Vienna, Austria.
RP Muller, BG (reprint author), Univ Amsterdam, Acad Med Ctr, Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands.
EM b.g.muller@amc.uva.nl
RI Krammel, Vera/N-4826-2014; Arnauld, VILLERS/K-6629-2016;
OI Krammel, Vera/0000-0002-8273-8396; Arnauld, VILLERS/0000-0002-6298-7758;
Gontero, Paolo/0000-0002-9714-6596
FU Cure for Cancer Foundation
FX B.G.M. and W.v.d.B. received an unrestricted research grant from the
Cure for Cancer Foundation.
NR 28
TC 10
Z9 10
U1 0
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1464-4096
EI 1464-410X
J9 BJU INT
JI BJU Int.
PD NOV
PY 2014
VL 114
IS 5
BP 698
EP 707
DI 10.1111/bju.12548
PG 10
WC Urology & Nephrology
SC Urology & Nephrology
GA AS4NY
UT WOS:000344254100015
PM 24180365
ER
PT J
AU Miller, KD
Althouse, SK
Nabell, L
Rugo, H
Carey, L
Kimmick, G
Jones, DR
Merino, MJ
Steeg, PS
AF Miller, Kathy D.
Althouse, Sandra K.
Nabell, Lisle
Rugo, Hope
Carey, Lisa
Kimmick, Gretchen
Jones, David R.
Merino, Maria J.
Steeg, Patricia S.
TI A phase II study of medroxyprogesterone acetate in patients with hormone
receptor negative metastatic breast cancer: translational breast cancer
research consortium trial 007
SO BREAST CANCER RESEARCH AND TREATMENT
LA English
DT Article
DE Glucocorticoid receptor; Metastasis suppressor gene; Angiogenesis;
Thrombospondin-1; Nm023; Plasminogen activator inhibitor type I
ID ENDOTHELIAL GROWTH-FACTOR; SUPPRESSOR GENE-EXPRESSION; ENDOGENOUS
THROMBOSPONDIN-1; GLUCOCORTICOID-RECEPTOR; RANDOMIZED TRIAL; NM23-H1;
TAMOXIFEN; PLATELET; TUMORS; CELLS
AB Preclinical data suggest that medroxyprogesterone acetate (MPA) has both anti-metastatic and anti-angiogenic activity in the absence of hormone receptors (HR). This phase II trial assessed the activity of MPA alone or in combination with low-dose chemotherapy in patients with metastatic HR-negative breast cancer. Postmenopausal women with HR-negative disease were eligible if they had not received more than 3 chemotherapy regimens for metastatic disease. All patients were treated with MPA 1,000-1,500 mg/day orally; patients in cohort two also received low-dose oral cyclophosphamide and methotrexate (ldCM, 50 mg/day and 2.5 mg twice daily on Days 1 and 2 each week). Tissue and circulating biomarkers were assessed serially. The primary endpoint was clinical benefit response defined as objective response or stable disease > 6 months. Thirty patients were enrolled (14 MPA monotherapy; 16 MPA + ldCM); median age was 55 (35-80); nearly all had visceral involvement. Despite dose escalation in 90 % of patients, only 17 (57 %) patients ever achieved MPA trough concentrations > 50 ng/ml. One patient developed grade 4 renal failure in the setting of rapid disease progression and dehydration. There were no objective responses. One patient in each cohort (similar to 7 %) had stable disease for > 6 months. Skin Nm23 expression increased after 4 weeks of MPA + ldCM, but there were no significant changes in TSP-1, PAI-1 antigen, or PAI-1 activity. MPA had limited activity and does not warrant further development in patients with HR-negative advanced breast cancer. Poor bioavailability limited exposure despite dose escalation.
C1 [Miller, Kathy D.; Althouse, Sandra K.; Jones, David R.] Indiana Univ, Melvin & Bren Simon Canc Ctr, Indianapolis, IN 46202 USA.
[Nabell, Lisle] Univ Alabama Birmingham, Birmingham, AL USA.
[Rugo, Hope] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Carey, Lisa] Univ N Carolina, Chapel Hill, NC USA.
[Kimmick, Gretchen] Duke Univ, Med Ctr, Durham, NC 27706 USA.
[Merino, Maria J.] NCI, Pathol Lab, Bethesda, MD 20892 USA.
[Steeg, Patricia S.] NCI, Womens Malignancies Branch, Bethesda, MD 20892 USA.
RP Miller, KD (reprint author), Indiana Univ, Melvin & Bren Simon Canc Ctr, 535 Barnhill Dr,RT 473, Indianapolis, IN 46202 USA.
EM kathmill@iupui.edu
FU NIH/NCI [P30 CA082709-AV-133]; Breast Cancer Research Foundation; AVON
Foundation; Susan G. Komen for the Cure
FX Supported by NIH/NCI P30 CA082709-AV-133 (Avon Partners for Progress
Supplement) and the Breast Cancer Research Foundation (KDM). In
addition, we are grateful for the funding support to the Translational
Breast Cancer Research Consortium (TBCRC) from The AVON Foundation, The
Breast Cancer Research Foundation, and Susan G. Komen for the Cure.
NR 37
TC 3
Z9 3
U1 0
U2 7
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 NOV
PY 2014
VL 148
IS 1
BP 99
EP 106
DI 10.1007/s10549-014-3131-3
PG 8
WC Oncology
SC Oncology
GA AR8DT
UT WOS:000343806400010
PM 25257727
ER
PT J
AU Goldman, S
Smith, L
Galardy, P
Perkins, SL
Frazer, JK
Sanger, W
Anderson, JR
Gross, TG
Weinstein, H
Harrison, L
Shiramizu, B
Barth, M
Cairo, MS
AF Goldman, Stanton
Smith, Lynette
Galardy, Paul
Perkins, Sherrie L.
Frazer, John Kimble
Sanger, Warren
Anderson, James R.
Gross, Thomas G.
Weinstein, Howard
Harrison, Lauren
Shiramizu, Bruce
Barth, Matthew
Cairo, Mitchell S.
TI Rituximab with chemotherapy in children and adolescents with central
nervous system and/or bone marrow-positive Burkitt lymphoma/leukaemia: a
Children's Oncology Group Report
SO BRITISH JOURNAL OF HAEMATOLOGY
LA English
DT Article
DE children; Burkitt lymphoma; Burkitt leukaemia; chemotherapy; rituximab
ID NON-HODGKINS-LYMPHOMA; B-CELL LYMPHOMA; ACUTE-LYMPHOBLASTIC-LEUKEMIA;
PLUS RITUXIMAB; ADULT BURKITT; CODOX-M/IVAC; PHASE-II; RISK;
INTERMEDIATE; THERAPY
AB Children and adolescents with Burkitt Lymphoma (BL) and combined central nervous system (CNS) and bone marrow involvement still have a poor prognosis with chemotherapy alone. We therefore investigated in children and adolescents with bone marrow (25% blasts) and/or CNS-positive Burkitt lymphoma the chemoimmunotherapy combination of rituximab (375mg/m(2)) and the standard chemotherapy arm of our previously reported French-American-British (FAB) Lymphome Malins de Burkitt (LMB) 96 trial. Central pathological and cytogenetic characterization was also performed. There were 40 evaluable patients with Burkitt histology (25 with leukaemia and 15 with CNS disease +/- leukaemia). The chemoimmunotherapy regimen was well tolerated. The incidence of grade III/IV mucositis during induction cycles with combined chemotherapy and rituximab was 31% and 26%, respectively. The 3-year event-free survival (EFS)/overall survival (OS) was 90% (95% confidence interval [CI], 76-96%) in the entire cohort and 93% (95% CI, 61-99%) in patients with CNS disease. Based on the results of this trial, an international randomized study of FAB/LMB 96 chemotherapy +/- rituximab for high-risk patients is currently under investigation.
C1 [Goldman, Stanton] Med City Childrens Hosp, Div Pediat Hematol Oncol, Dallas, TX USA.
[Smith, Lynette; Anderson, James R.] Univ Nebraska, Coll Publ Hlth, Dept Biostat, Omaha, NE 68182 USA.
[Galardy, Paul] Mayo Clin, Dept Pediat Hematol Oncol, Rochester, MN USA.
[Perkins, Sherrie L.] Univ Utah, Dept Pathol, Salt Lake City, UT USA.
[Frazer, John Kimble] Univ Oklahoma, Hlth Sci Ctr, Sect Pediat Hematol Oncol, Oklahoma City, OK USA.
[Sanger, Warren] Univ Nebraska, Ctr Human Genet, Omaha, NE 68182 USA.
[Gross, Thomas G.] NCI, Ctr Global Hlth, NIH, Rockville, MD USA.
[Weinstein, Howard] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Pediat Hematol Oncol, Boston, MA USA.
[Harrison, Lauren; Cairo, Mitchell S.] New York Med Coll, Dept Pediat, Valhalla, NY 10595 USA.
[Shiramizu, Bruce] Univ Hawaii, Div Pediat Hematol Oncol, Honolulu, HI 96822 USA.
[Barth, Matthew] Roswell Pk Canc Inst, Dept Pediat, Buffalo, NY 14263 USA.
[Cairo, Mitchell S.] New York Med Coll, Dept Med, Valhalla, NY 10595 USA.
[Cairo, Mitchell S.] New York Med Coll, Dept Pathol, Valhalla, NY 10595 USA.
[Cairo, Mitchell S.] New York Med Coll, Dept Microbiol & Immunol, Valhalla, NY 10595 USA.
[Cairo, Mitchell S.] New York Med Coll, Dept Cell Biol & Anat, Valhalla, NY 10595 USA.
RP Cairo, MS (reprint author), New York Med Coll, Div Pediat Hematol Oncol & Stem Cell Transplantat, 40 Sunshine Cottage Rd,Skyline IN D12, Valhalla, NY 10595 USA.
EM Mitchell_cairo@nymc.edu
OI Frazer, John Kimble/0000-0003-2936-2817
FU Division of Cancer Treatment, National Cancer Institute (NCI); National
Institutes of Health, Department of Health and Human Services (COG)
[CA98413-09]; Pediatric Cancer Research Foundation; National Institutes
of Health, Department of Health and Human Services (COG) (jn)
FX Supported by the Division of Cancer Treatment, National Cancer Institute
(NCI), and National Institutes of Health, Department of Health and Human
Services (COG) (jn and CA98413-09) and the Pediatric Cancer Research
Foundation. NCI provided support for data collection and analysis but no
role in data interpretation, writing of the manuscript or the decision
on journal submission.
NR 22
TC 19
Z9 19
U1 0
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0007-1048
EI 1365-2141
J9 BRIT J HAEMATOL
JI Br. J. Haematol.
PD NOV
PY 2014
VL 167
IS 3
BP 394
EP 401
DI 10.1111/bjh.13040
PG 8
WC Hematology
SC Hematology
GA AS0MB
UT WOS:000343970000012
PM 25066629
ER
PT J
AU Natarajan, G
Shankaran, S
Pappas, A
Bann, C
Tyson, JE
McDonald, S
Das, A
Hintz, S
Vohr, B
Higgins, R
AF Natarajan, Girija
Shankaran, Seetha
Pappas, Athina
Bann, Carla
Tyson, Jon E.
McDonald, Scott
Das, Abhik
Hintz, Susan
Vohr, Betty
Higgins, Rosemary
CA Eunice Kennedy Shriver Natl Inst
TI Functional status at 18 months of age as a predictor of childhood
disability after neonatal hypoxic-ischemic encephalopathy
SO DEVELOPMENTAL MEDICINE AND CHILD NEUROLOGY
LA English
DT Article
ID BIRTH-WEIGHT INFANTS; QUALITY-OF-LIFE; HEALTH-STATUS; CEREBRAL-PALSY;
FAMILY SCALE; CHILDREN; QUESTIONNAIRE; OUTCOMES; IMPACT; HYPOTHERMIA
AB AimIn children with neonatal hypoxic-ischemic encephalopathy (HIE), we examined the association between 18-month functional status by parental report and disability at 6-7 years.
MethodProspective observational study involving participants in the NICHD randomized controlled trial of hypothermia for HIE. Parent questionnaires-Functional Status-II (FS-II), Impact on Family (IOF) and Family Resource Scale (FRS) at 18 months were correlated with 6- to 7-year developmental assessments. Disability at 6-7 years was defined as IQ < 70, gross motor functional classification scale level III-V, bilateral blindness, deafness, or epilepsy.
ResultsRates of severe HIE (32 vs. 15%), public insurance (73% vs. 47%) and IOF scales were higher and mean (SD) FS-II independence (I) {54 (SD 35) vs. 98 (SD 8)} and general health (GH) {87 (SD 14) vs. 98 (SD 6)} scores were significantly lower in children with disability (n=37) at 6-7 years, compared to those (n=74) without disability. FS-II I scores were significantly associated with disability (OR 0.92; 95% CI 0.87-0.97; p=0.003). On path analysis, severe HIE, greater IOF and public insurance were associated with poorer 18-month FS-II I scores, which, in turn, were associated with disability at 6 to 7 years.
InterpretationPoor independent functioning by parental report at 18 months in children with HIE was associated with childhood disability.
C1 [Natarajan, Girija; Shankaran, Seetha; Pappas, Athina] Wayne State Univ, Dept Pediat, Detroit, MI 48202 USA.
[Bann, Carla; McDonald, Scott] RTI Int, Social Stat & Environm Sci Unit, Res Triangle Pk, NC USA.
[Tyson, Jon E.] Univ Texas Med Sch Houston, Dept Pediat, Houston, TX USA.
[Das, Abhik] Res Triangle Int, Social Stat & Environm Sci Unit, Rockville, MD USA.
[Hintz, Susan] Stanford Univ, Sch Med, Dept Pediat, Palo Alto, CA 94304 USA.
[Vohr, Betty] Brown Univ, Women & Infants Hosp, Dept Pediat, Providence, RI 02908 USA.
[Higgins, Rosemary] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
RP Natarajan, G (reprint author), Childrens Hosp Michigan, Dept Pediat, Div Neonatol, 3901 Beaubien Blvd, Detroit, MI 48201 USA.
EM gnatara@med.wayne.edu
FU National Institutes of Health; Eunice Kennedy Shriver National Institute
of Child Health and Human Development
FX The National Institutes of Health and the Eunice Kennedy Shriver
National Institute of Child Health and Human Development provided grant
support for the Neonatal Research Network's Whole-Body Hypothermia Trial
and its 18- to 22-month and 6- to 7-year follow-up studies through
cooperative agreements. While NICHD staff did have input into the study
design, conduct, analysis, and manuscript drafting, the comments and
views of the authors do not necessarily represent the views of the
NICHD. Data collected at participating sites of the NICHD Neonatal
Research Network were transmitted to RTI International, the data
coordinating center for the network, which stored, managed and analyzed
the data for this study. On behalf of the NRN, Dr Abhik Das (data
coordinating center Principal Investigator) and Mr Scott A McDonald
(data coordinating center Statistician) had full access to all the data
in the study and take responsibility for the integrity of the data and
accuracy of the data analysis. We are indebted to our medical and
nursing colleagues and the infants and their parents who agreed to take
part in this study. The following investigators, in addition to those
listed as authors, participated in this study: a detailed
acknowledgement of all involved investigators is included in Appendix
S1.
NR 29
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U1 1
U2 5
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0012-1622
EI 1469-8749
J9 DEV MED CHILD NEUROL
JI Dev. Med. Child Neurol.
PD NOV
PY 2014
VL 56
IS 11
BP 1052
EP 1058
DI 10.1111/dmcn.12512
PG 7
WC Clinical Neurology; Pediatrics
SC Neurosciences & Neurology; Pediatrics
GA AR8CM
UT WOS:000343803100012
PM 24957482
ER
PT J
AU Muniyappa, R
Srinivas, PR
AF Muniyappa, Ranganath
Srinivas, Pothur R.
TI Dicarbonyl Stress and Atherosclerosis: Is It All RAGE?
SO DIABETES
LA English
DT Editorial Material
ID GLYCATION END-PRODUCTS; GLYOXALASE-I; CARDIOVASCULAR-DISEASE;
DEGRADATION-PRODUCTS; OXIDATIVE STRESS; RECEPTOR; OVEREXPRESSION;
HYPERGLYCEMIA; ENDPRODUCTS; MECHANISMS
C1 [Muniyappa, Ranganath] NIDDK, Clin Endocrine Sect, Diabet Endocrinol & Obes Branch, Bethesda, MD 20892 USA.
[Srinivas, Pothur R.] NHLBI, Div Cardiovasc Sci, NIH, Bethesda, MD 20892 USA.
RP Muniyappa, R (reprint author), NIDDK, Clin Endocrine Sect, Diabet Endocrinol & Obes Branch, Bethesda, MD 20892 USA.
EM muniyapr@mail.nih.gov
FU Intramural NIH HHS
NR 25
TC 2
Z9 2
U1 1
U2 3
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0012-1797
EI 1939-327X
J9 DIABETES
JI Diabetes
PD NOV
PY 2014
VL 63
IS 11
BP 3587
EP 3589
DI 10.2337/db14-0953
PG 3
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA AS0KM
UT WOS:000343966100007
PM 25342731
ER
PT J
AU Lee, P
Smith, S
Linderman, J
Courville, AB
Brychta, RJ
Dieckmann, W
Werner, CD
Chen, KY
Celi, FS
AF Lee, Paul
Smith, Sheila
Linderman, Joyce
Courville, Amber B.
Brychta, Robert J.
Dieckmann, William
Werner, Charlotte D.
Chen, Kong Y.
Celi, Francesco S.
TI Temperature-Acclimated Brown Adipose Tissue Modulates Insulin
Sensitivity in Humans
SO DIABETES
LA English
DT Article
ID DIET-INDUCED THERMOGENESIS; COLD-INDUCED THERMOGENESIS; ADULT HUMANS;
ENERGY-EXPENDITURE; FAT; OBESITY; EXPOSURE; BEIGE; MICE; IDENTIFICATION
AB In rodents, brown adipose tissue (BAT) regulates cold- and diet-induced thermogenesis (CIT; DIT). Whether BAT recruitment is reversible and how it impacts on energy metabolism have not been investigated in humans. We examined the effects of temperature acclimation on BAT, energy balance, and substrate metabolism in a prospective crossover study of 4-month duration, consisting of four consecutive blocks of 1-month overnight temperature acclimation (24 degrees C [month 1] -> 19 degrees C [month 2] -> 24 degrees C [month 3] -> 27 degrees C [month 4]) of five healthy men in a temperature-controlled research facility. Sequential monthly acclimation modulated BAT reversibly, boosting and suppressing its abundance and activity in mild cold and warm conditions (P < 0.05), respectively, independent of seasonal fluctuations (P < 0.01). BAT acclimation did not alter CIT but was accompanied by DIT (P < 0.05) and postprandial insulin sensitivity enhancement (P < 0.05), evident only after cold acclimation. Circulating and adipose tissue, but not skeletal muscle, expression levels of leptin and adiponectin displayed reciprocal changes concordant with cold-acclimated insulin sensitization. These results suggest regulatory links between BAT thermal plasticity and glucose metabolism in humans, opening avenues to harnessing BAT for metabolic benefits.
C1 [Lee, Paul; Smith, Sheila; Linderman, Joyce; Brychta, Robert J.; Werner, Charlotte D.; Chen, Kong Y.; Celi, Francesco S.] NIDDK, Diabet Endocrinol & Obes Branch, Bethesda, MD 20892 USA.
[Courville, Amber B.] NIH, Dept Nutr, Ctr Clin, Bethesda, MD 20892 USA.
[Dieckmann, William] NIH, PET Dept, Ctr Clin, Bethesda, MD 20892 USA.
[Celi, Francesco S.] Virginia Commonwealth Univ, Div Endocrinol & Metab, Richmond, VA USA.
RP Celi, FS (reprint author), NIDDK, Diabet Endocrinol & Obes Branch, Bethesda, MD 20892 USA.
EM fsceli@vcu.edu
OI Chen, Kong/0000-0002-0306-1904
FU NIDDK [Z01-DK047057-07]; NIH Clinical Center; Australian National Health
and Medical Research Council Early Career Fellowship; Diabetes Australia
Fellowship; Bushell Travelling Fellowship; School of Medicine,
University of Queensland
FX This study was supported by the Intramural Research Program
Z01-DK047057-07 of NIDDK and the NIH Clinical Center. P.L. was supported
by an Australian National Health and Medical Research Council Early
Career Fellowship, the Diabetes Australia Fellowship and Bushell
Travelling Fellowship, and the School of Medicine, University of
Queensland.
NR 50
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U1 5
U2 20
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0012-1797
EI 1939-327X
J9 DIABETES
JI Diabetes
PD NOV
PY 2014
VL 63
IS 11
BP 3686
EP 3698
DI 10.2337/db14-0513
PG 13
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA AS0KM
UT WOS:000343966100018
PM 24954193
ER
PT J
AU Kang, L
Dai, CH
Lustig, ME
Bonner, JS
Mayes, WH
Mokshagundam, S
James, FD
Thompson, CS
Lin, CT
Perry, CGR
Anderson, EJ
Neufer, PD
Wasserman, DH
Powers, AC
AF Kang, Li
Dai, Chunhua
Lustig, Mary E.
Bonner, Jeffrey S.
Mayes, Wesley H.
Mokshagundam, Shilpa
James, Freyja D.
Thompson, Courtney S.
Lin, Chien-Te
Perry, Christopher G. R.
Anderson, Ethan J.
Neufer, P. Darrell
Wasserman, David H.
Powers, Alvin C.
TI Heterozygous SOD2 Deletion Impairs Glucose-Stimulated Insulin Secretion,
but Not Insulin Action, in High-Fat-Fed Mice
SO DIABETES
LA English
DT Article
ID BETA-CELL DYSFUNCTION; OXIDATIVE STRESS; SUPEROXIDE-DISMUTASE;
GLUTATHIONE-PEROXIDASE; DILATED CARDIOMYOPATHY; DIABETES-MELLITUS;
HYDROGEN-PEROXIDE; CONSCIOUS MOUSE; MUTANT MICE; P38 MAPK
AB Elevated reactive oxygen species (ROS) are linked to insulin resistance and islet dysfunction. Manganese superoxide dismutase (SOD2) is a primary defense against mitochondrial oxidative stress. To test the hypothesis that heterozygous SOD2 deletion impairs glucose-stimulated insulin secretion (GSIS) and insulin action, wild-type (sod2(+/+)) and heterozygous knockout mice (sod2(+/-)) were fed a chow or high-fat (HF) diet, which accelerates ROS production. Hyperglycemic (HG) and hyperinsulinemic-euglycemic (HI) clamps were performed to assess GSIS and insulin action in vivo. GSIS during HG clamps was equal in chow-fed sod2(+/-) and sod2(+/+) but was markedly decreased in HF-fed sod2(+/-). Remarkably, this impairment was not paralleled by reduced HG glucose infusion rate (GIR). Decreased GSIS in HF-fed sod2(+/-) was associated with increased ROS, such as superoxide ion. Surprisingly, insulin action determined by HI clamps did not differ between sod2(+/-) and sod2(+/+) of either diet. Since insulin action was unaffected, we hypothesized that the unchanged HG GIR in HF-fed sod2(+/-) was due to increased glucose effectiveness. Increased GLUT-1, hexokinase II, and phospho-AMPK protein in muscle of HF-fed sod2(+/-) support this hypothesis. We conclude that heterozygous SOD2 deletion in mice, a model that mimics SOD2 changes observed in diabetic humans, impairs GSIS in HF-fed mice without affecting insulin action.
C1 [Kang, Li; Lustig, Mary E.; Bonner, Jeffrey S.; Mayes, Wesley H.; Mokshagundam, Shilpa; James, Freyja D.; Wasserman, David H.; Powers, Alvin C.] Vanderbilt Univ, Dept Mol Physiol & Biophys, Nashville, TN 37232 USA.
[Kang, Li; Wasserman, David H.] Vanderbilt Univ, Mouse Metab Phenotyping Ctr, Nashville, TN 37232 USA.
[Kang, Li] Univ Dundee, Ninewells Hosp & Med Sch, Div Cardiovasc & Diabet Med, Dundee DD1 9SY, Scotland.
[Dai, Chunhua; Thompson, Courtney S.; Powers, Alvin C.] Vanderbilt Univ, Dept Med, Div Diabet Endocrinol & Metab, Nashville, TN 37232 USA.
[Lin, Chien-Te; Perry, Christopher G. R.; Anderson, Ethan J.; Neufer, P. Darrell] E Carolina Univ, East Carolina Diabet & Obes Inst, Greenville, NC USA.
[Lin, Chien-Te; Perry, Christopher G. R.; Anderson, Ethan J.; Neufer, P. Darrell] E Carolina Univ, Dept Physiol, Greenville, NC USA.
[Lin, Chien-Te; Perry, Christopher G. R.; Anderson, Ethan J.; Neufer, P. Darrell] E Carolina Univ, Dept Kinesiol, Greenville, NC USA.
[Powers, Alvin C.] Vet Affairs Tennessee Valley Healthcare Syst, Nashville, TN USA.
RP Kang, L (reprint author), Vanderbilt Univ, Dept Mol Physiol & Biophys, Nashville, TN 37232 USA.
EM l.kang@dundee.ac.uk
FU National Institutes of Health (NIH) [DK-054902]; NIH [DK-059637,
DK-69603, DK-089572, DK-089538, DK-66636, DK-072473]; Merit Review Award
from the Veterans Affairs Research Service [BX000666]; JDRF
International; Vanderbilt Diabetes Research and Training Center (NIH)
[DK-20593]
FX This work was supported by National Institutes of Health (NIH) grant
DK-054902 (to D.H.W.); NIH grant DK-059637 (Mouse Metabolic Phenotyping
Center, to D.H.W.); a Merit Review Award from the Veterans Affairs
Research Service (BX000666 to A.C.P.); NIH grants DK-69603, DK-089572,
DK-089538, DK-66636, and DK-072473 (to A.C.P.); grants from JDRF
International; and the Vanderbilt Diabetes Research and Training Center
(NIH grant DK-20593). The authors received no editorial assistance.
NR 44
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U1 0
U2 5
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0012-1797
EI 1939-327X
J9 DIABETES
JI Diabetes
PD NOV
PY 2014
VL 63
IS 11
BP 3699
EP 3710
DI 10.2337/db13-1845
PG 12
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA AS0KM
UT WOS:000343966100019
PM 24947366
ER
PT J
AU Lawrence, JM
Imperatore, G
Dabelea, D
Mayer-Davis, EJ
Linder, B
Saydah, S
Klingensmith, GJ
Dolan, L
Standiford, DA
Pihoker, C
Pettitt, DJ
Talton, JW
Thomas, J
Bell, RA
D'Agostino, RB
AF Lawrence, Jean M.
Imperatore, Giuseppina
Dabelea, Dana
Mayer-Davis, Elizabeth J.
Linder, Barbara
Saydah, Sharon
Klingensmith, Georgeanna J.
Dolan, Lawrence
Standiford, Debra A.
Pihoker, Catherine
Pettitt, David J.
Talton, Jennifer W.
Thomas, Joan
Bell, Ronny A.
D'Agostino, Ralph B., Jr.
CA SEARCH Diabet Youth Study Grp
TI Trends in Incidence of Type 1 Diabetes Among Non-Hispanic White Youth in
the U.S., 2002-2009
SO DIABETES
LA English
DT Article
ID CHILDHOOD TYPE-1; TIME TRENDS; PROSPECTIVE REGISTRATION; INCREASING
INCIDENCE; CHILDREN; SWEDEN; WORLDWIDE; MELLITUS; MULTICENTER;
PREVALENCE
AB The SEARCH for Diabetes in Youth Study prospectively identified youth aged <20 years with physician-diagnosed diabetes. Annual type 1 diabetes (T1D) incidence per 100,000 person-years (95% Cl) overall, by age-group, and by sex were calculated for at-risk non-Hispanic white (NHVV) youth from 2002 through 2009. Joinpoint and Poisson regression models were used to test for temporal trends. The age- and sex-adjusted incidence of T1D increased from 24.4/100,000 (95% CI 23.9-24.8) in 2002 to 27.4/100,000 (26.9-27.9) in 2009 (P for trend = 0.0008). The relative annual increase in T1D incidence was 2.72% (1.18-4.28) per year; 2.84% (1.12-4.58) per year for males and 2.57% (0.68-4.51) per year for females. After adjustment for sex, significant increases were found for youth aged 5-9 years (P = 0.0023), 10-14 years (P = 0.0008), and 15-19 years (P = 0.004) but not among 0-4-year-olds (P = 0.1862). Mean age at diagnosis did not change. The SEARCH study demonstrated a significant increase in the incidence of T1D among NHW youth from 2002 through 2009 overall and in all but the youngest agegroup. Continued surveillance of T1D in U.S. youth to identify future trends in T1D incidence and to plan for health care delivery is warranted.
C1 [Lawrence, Jean M.] Kaiser Permanente So Calif, Dept Res & Evaluat, Pasadena, CA 91101 USA.
[Imperatore, Giuseppina] Ctr Dis Control & Prevent, Div Diabet Translat, Atlanta, GA USA.
[Dabelea, Dana] Univ Colorado Denver, Colorado Sch Publ Hlth, Dept Epidemiol, Aurora, CO USA.
[Mayer-Davis, Elizabeth J.; Thomas, Joan] Univ N Carolina, Gillings Sch Global Publ Hlth, Dept Nutr, Chapel Hill, NC USA.
[Mayer-Davis, Elizabeth J.] Univ N Carolina, Sch Med, Chapel Hill, NC USA.
[Linder, Barbara] NIDDK, NIH, Bethesda, MD USA.
[Saydah, Sharon] Ctr Dis Control & Prevent, Div Diabet Translat, Hyattsville, MD USA.
[Klingensmith, Georgeanna J.] Univ Colorado Denver, Sch Med, Barbara Davis Ctr, Aurora, CO USA.
[Dolan, Lawrence; Standiford, Debra A.] Cincinnati Childrens Hosp Med Ctr, Div Endocrinol, Cincinnati, OH 45229 USA.
[Dolan, Lawrence] Univ Cincinnati, Dept Pediat, Cincinnati, OH USA.
[Pihoker, Catherine] Univ Washington, Dept Pediat, Seattle, WA 98195 USA.
[Pettitt, David J.] Sansum Diabet Res Inst, Santa Barbara, CA USA.
[Talton, Jennifer W.; D'Agostino, Ralph B., Jr.] Wake Forest Sch Med, Dept Biostat Sci, Winston Salem, NC USA.
[Bell, Ronny A.] Wake Forest Sch Med, Dept Epidemiol & Prevent, Winston Salem, NC USA.
RP Lawrence, JM (reprint author), Kaiser Permanente So Calif, Dept Res & Evaluat, Pasadena, CA 91101 USA.
EM jean.m.lawrence@kp.org
RI Dagostino Jr, Ralph/C-4060-2017
OI Dagostino Jr, Ralph/0000-0002-3550-8395
FU Centers for Disease Control and Prevention [00097, DP-05-069,
DP-10-001]; National Institute of Diabetes and Digestive and Kidney
Diseases; Kaiser Permanente Southern California [U48/CCU919219,
U01-DP-000246, U18-DP-002714]; University of Colorado Denver
[U48/CCU819241-3, U01-DP-000247, U18-DP-000247-06A1]; Children's
Hospital Medical Center (Cincinnati) [U48/CCU519239, U01-DP-000248,
1U18-DP002709]; University of North Carolina at Chapel Hill
[U48/CCU419249, U01-DP000254, U18-DP-002708-01]; University of
Washington School of Medicine [U58/CCU019235-4, U01-DP-000244,
U18-DP-002710-01]; Wake Forest School of Medicine [U48/CCU919219,
U01-DP-000250, 200-2010-35171]; General Clinical Research Centers at the
South Carolina Clinical and Translational Research Institute at the
Medical University of South Carolina (National Institutes of
Health/National Center for Research Resources) [UURR029882]; Seattle
Children's Hospital (National Institutes of Health Clinical and
Translational Science Awards of the University of Washington) [UL1
TR00423]; University of Colorado Pediatric Clinical and Translational
Research Center [UL1 TR000154]; Barbara Davis Center at the University
of Colorado Denver (DERC NIH) [P30 DK57516]; National Center for
Research Resources; National Center for Advancing Translational
Sciences, National Institutes of Health [8 UL1 TR000077]; Children with
Medical Handicaps program
FX SEARCH for Diabetes in Youth Study is funded by the Centers for Disease
Control and Prevention (PA numbers 00097, DP-05-069, and DP-10-001) and
supported by the National Institute of Diabetes and Digestive and Kidney
Diseases. Contract numbers: Kaiser Permanente Southern California
(U48/CCU919219, U01-DP-000246, and U18-DP-002714), University of
Colorado Denver (U48/CCU819241-3, U01-DP-000247, and
U18-DP-000247-06A1), Children's Hospital Medical Center (Cincinnati)
(U48/CCU519239, U01-DP-000248, and 1U18-DP002709), University of North
Carolina at Chapel Hill (U48/CCU419249, U01-DP000254, and
U18-DP-002708-01), University of Washington School of Medicine
(U58/CCU019235-4, U01-DP-000244, and U18-DP-002710-01), and Wake Forest
School of Medicine (U48/CCU919219, U01-DP-000250, and 200-2010-35171).
The authors wish to acknowledge the involvement of General Clinical
Research Centers at the South Carolina Clinical and Translational
Research Institute at the Medical University of South Carolina (National
Institutes of Health/National Center for Research Resources grant number
UURR029882); Seattle Children's Hospital (National Institutes of Health
Clinical and Translational Science Awards grant UL1 TR00423 of the
University of Washington); University of Colorado Pediatric Clinical and
Translational Research Center (grant number UL1 TR000154); the Barbara
Davis Center at the University of Colorado Denver (DERC NIH P30
DK57516); the National Center for Research Resources and the National
Center for Advancing Translational Sciences, National Institutes of
Health, through grant 8 UL1 TR000077; and the Children with Medical
Handicaps program managed by the Ohio Department of Health.
NR 26
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PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0012-1797
EI 1939-327X
J9 DIABETES
JI Diabetes
PD NOV
PY 2014
VL 63
IS 11
BP 3938
EP 3945
DI 10.2337/db13-1891
PG 8
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA AS0KM
UT WOS:000343966100041
PM 24898146
ER
PT J
AU Chen, YG
Cabrera, SM
Jia, S
Kaldunski, ML
Kramer, J
Cheong, S
Geoffrey, R
Roethle, MF
Woodliff, JE
Greenbaum, CJ
Wang, XJ
Hessner, MJ
AF Chen, Yi-Guang
Cabrera, Susanne M.
Jia, Shuang
Kaldunski, Mary L.
Kramer, Joanna
Cheong, Sami
Geoffrey, Rhonda
Roethle, Mark F.
Woodliff, Jeffrey E.
Greenbaum, Carla J.
Wang, Xujing
Hessner, Martin J.
TI Molecular Signatures Differentiate Immune States in Type 1 Diabetic
Families
SO DIABETES
LA English
DT Article
ID INCREASED INTESTINAL PERMEABILITY; TRANSCRIPTION FACTOR FOXP3; DR-DQ
HAPLOTYPES; T-CELL RESPONSES; INFLAMMATORY BIOMARKER; MELLITUS;
RELATIVES; DISEASE; PREDICTION; SERUM
AB Mechanisms associated with type 1 diabetes (T1D) development remain incompletely defined. Using a sensitive array-based bioassay where patient plasma is used to induce transcriptional responses in healthy leukocytes, we previously reported disease-specific, partially interleukin (IL)-1-dependent signatures associated with preonset and recent onset (RO) T1D relative to unrelated healthy control subjects (uHC). To better understand inherited susceptibility in T1D families, we conducted cross-sectional and longitudinal analyses of healthy autoantibody-negative (AA(-)) high HLA-risk siblings (HRS) (DR3 and/or DR4) and AA(-) low HLA-risk siblings (LRS) (non-DR3/non-DR4). Signatures, scored with a novel ontology-based algorithm, and confirmatory studies differentiated the RO Ti D, uHC, HRS, and LRS plasma milieus. Relative to uHC, T1D family members exhibited an elevated inflammatory state, consistent with innate receptor ligation that was independent of HLA, AA, or disease status and included elevated plasma IL-la, IL-12p40, CCL2, CCL3, and CCL4 levels. Longitudinally, signatures of T1D progressors exhibited increasing inflammatory bias. Conversely, HRS possessing decreasing AA titers revealed emergence of an IL-10/transforming growth factor-beta-mediated regulatory state that paralleled temporal increases in peripheral activated CD4(+)/CD45RA(-)/FoxP3(high) regulatory 1-cell frequencies. In AA- HRS, the familial innate inflammatory state also was temporally supplanted by immunoregulatory processes, suggesting a mechanism underlying the decline in T1D susceptibility with age.
C1 [Chen, Yi-Guang; Cabrera, Susanne M.; Jia, Shuang; Kaldunski, Mary L.; Kramer, Joanna; Geoffrey, Rhonda; Roethle, Mark F.; Hessner, Martin J.] Childrens Hosp Wisconsin, Childrens Res Inst, Max McGee Natl Res Ctr Juvenile Diabet, Milwaukee, WI 53201 USA.
[Chen, Yi-Guang; Cabrera, Susanne M.; Jia, Shuang; Kaldunski, Mary L.; Kramer, Joanna; Geoffrey, Rhonda; Roethle, Mark F.; Hessner, Martin J.] Med Coll Wisconsin, Dept Pediat, Milwaukee, WI 53226 USA.
[Cheong, Sami] Univ Wisconsin, Dept Math Sci, Milwaukee, WI 53201 USA.
[Woodliff, Jeffrey E.] Purdue Univ, Bindley Biosci Ctr, Flow Cytometry & Cell Separat Facil, W Lafayette, IN 47907 USA.
[Greenbaum, Carla J.] Benaroya Res Inst, Diabet Res Program, Seattle, WA USA.
[Wang, Xujing] NHLBI, Syst Biol Ctr, NIH, Bethesda, MD 20892 USA.
RP Hessner, MJ (reprint author), Childrens Hosp Wisconsin, Childrens Res Inst, Max McGee Natl Res Ctr Juvenile Diabet, Milwaukee, WI 53201 USA.
EM mhessner@mcw.edu
FU JDRF International [1-2008-1026, 5-2012-220, 17-2012-621]; American
Diabetes Association [7-12-BS-075]; National Institutes of Health
[R00DK077443, R01DK080100, R01AI078713, DP3DK098161, 1-UL1-RR031973];
Children's Hospital of Wisconsin Foundation
FX This work was supported by JDRF International (grants 1-2008-1026,
5-2012-220, 17-2012-621 to M.J.H.), American Diabetes Association (grant
7-12-BS-075 to M.J.H.), National Institutes of Health (grants
R00DK077443 to Y.-G.C., R01DK080100 to X.W., R01AI078713 to M.J.H.,
DP3DK098161 to C.J.G. and M.J.H., and 1-UL1-RR031973 to the Clinical and
Translational Science Institute of Southeast Wisconsin), and the
Children's Hospital of Wisconsin Foundation.
NR 49
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U2 7
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0012-1797
EI 1939-327X
J9 DIABETES
JI Diabetes
PD NOV
PY 2014
VL 63
IS 11
BP 3960
EP 3973
DI 10.2337/db14-0214
PG 14
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA AS0KM
UT WOS:000343966100044
PM 24760139
ER
PT J
AU Sweeney, EM
Thakur, KT
Lyons, JL
Smith, BR
Willey, JZ
Cervantes-Arslanian, AM
Hickey, MK
Uchino, K
Haussen, DC
Koch, S
Schwamm, LH
Elkind, MSV
Shinohara, RT
Mateen, FJ
AF Sweeney, E. M.
Thakur, K. T.
Lyons, J. L.
Smith, B. R.
Willey, J. Z.
Cervantes-Arslanian, A. M.
Hickey, M. K.
Uchino, K.
Haussen, D. C.
Koch, S.
Schwamm, L. H.
Elkind, M. S. V.
Shinohara, R. T.
Mateen, F. J.
TI Outcomes of intravenous tissue plasminogen activator for acute ischaemic
stroke in HIV-infected adults
SO EUROPEAN JOURNAL OF NEUROLOGY
LA English
DT Article
DE cerebral infarction; cerebrovascular diseases and cerebral circulation;
HIV; infections; neurological disorders; stroke; thrombolysis
ID UNITED-STATES; RISK; EVENTS
AB Background and purposeTo our knowledge there are no studies reporting the use and short-term outcomes of intravenous tissue plasminogen activator (IV-TPA) for the treatment of acute ischaemic stroke (AIS) in people living with HIV.
MethodsThe US Nationwide Inpatient Sample (NIS) (2006-2010) was searched for HIV-infected AIS patients treated with IV-TPA.
ResultsIn the NIS, 2.2% (62/2877) of HIV-infected AIS cases were thrombolyzed with IV-TPA (median age 52years, range 27-78, 32% female, 22% Caucasian) vs. 2.1% (19335/937896) of HIV-uninfected cases (median age 72years, range 17-102years, 50% female, 74% Caucasian; P=0.77). There were more deaths in HIV-infected versus uninfected patients with stroke (220/2877, 7.6% vs. 49089/937547, 5.2%, P<0.001) but no difference in the proportion of deaths amongst IV-TPA-treated patients. The age- and sex-adjusted odds ratio for death following IV-TPA administration in HIV-infected versus uninfected patients was 2.26 (95% CI 1.12, 4.58), but the interaction on mortality between HIV and IV-TPA use was not statistically significant, indicating no difference in risk of in-hospital death by HIV serostatus with IV-TPA use. A higher number of HIV-infected patients remained in hospital versus died or were discharged at both 10 and 30days (P<0.01 at 10 and 30days). No difference in the proportion of intracerebral hemorrhage in the two groups was found (P=0.362).
ConclusionsThe in-hospital mortality is higher amongst HIV-infected AIS patients than HIV-uninfected patients. However, the risk of death amongst HIV-infected patients treated with IV-TPA is similar to HIV-uninfected groups.
C1 [Sweeney, E. M.] Johns Hopkins Univ, Dept Biostat, Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA.
[Thakur, K. T.] Johns Hopkins Univ Hosp, Dept Neurol, Baltimore, MD 21287 USA.
[Lyons, J. L.] Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA.
[Smith, B. R.] NINDS, Sect Infect Nervous Syst, NIH, Bethesda, MD 20892 USA.
[Willey, J. Z.; Elkind, M. S. V.] Columbia Univ, Dept Neurol, Coll Phys & Surg, New York, NY USA.
[Cervantes-Arslanian, A. M.] Boston Univ, Dept Neurol, Boston, MA 02215 USA.
[Hickey, M. K.; Schwamm, L. H.; Mateen, F. J.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
[Uchino, K.] Cleveland Clin, Cerebrovasc Ctr, Cleveland, OH 44106 USA.
[Haussen, D. C.; Koch, S.] Univ Miami, Dept Neurol, Miami, FL USA.
[Elkind, M. S. V.] Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY USA.
[Shinohara, R. T.] Univ Penn, Perelman Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA.
RP Mateen, FJ (reprint author), Massachusetts Gen Hosp, Dept Neurol, 55 Fruit St,AC-720, Boston, MA 02114 USA.
EM fmateen@partners.org
OI Schwamm, Lee/0000-0003-0592-9145
FU HIV/AIDS from Canadian Institute of Health Research (CIHR)
FX Dr Mateen received salary support from an HIV/AIDS priority grant from
the Canadian Institute of Health Research (CIHR).
NR 13
TC 3
Z9 4
U1 0
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1351-5101
EI 1468-1331
J9 EUR J NEUROL
JI Eur. J. Neurol.
PD NOV
PY 2014
VL 21
IS 11
BP 1394
EP 1399
DI 10.1111/ene.12506
PG 6
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA AR8EH
UT WOS:000343808000009
PM 25040336
ER
PT J
AU Telford, SR
Hu, LDT
Marques, A
AF Telford, Sam R., III
Hu, Linden T.
Marques, Adriana
TI Is there a place for xenodiagnosis in the clinic?
SO EXPERT REVIEW OF ANTI-INFECTIVE THERAPY
LA English
DT Editorial Material
DE Borrelia burgdorferi; clinical trial; Ixodes dammini; Lyme disease;
xenodiagnosis
ID BORRELIA-BURGDORFERI; LYME-DISEASE; ANTIBIOTIC-TREATMENT; MICE;
CEFTRIAXONE; PERSISTENCE; THERAPY; TICK; DOGS
C1 [Telford, Sam R., III] Tufts Univ, Cummings Sch Vet Med, North Grafton, MA 01536 USA.
[Hu, Linden T.] Tufts Med Ctr, Boston, MA 02115 USA.
[Marques, Adriana] NIAID, NIH, Bethesda, MD 20892 USA.
RP Telford, SR (reprint author), Tufts Univ, Cummings Sch Vet Med, North Grafton, MA 01536 USA.
EM sam.telford@tufts.edu
RI Hu, Linden/L-6314-2016
OI Hu, Linden/0000-0003-1659-5558
FU Intramural NIH HHS; NIAID NIH HHS [R21 AI082436, R21AI082436]
NR 28
TC 0
Z9 0
U1 0
U2 6
PU EXPERT REVIEWS
PI LONDON
PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB,
ENGLAND
SN 1478-7210
EI 1744-8336
J9 EXPERT REV ANTI-INFE
JI Expert Rev. Anti-Infect. Ther.
PD NOV
PY 2014
VL 12
IS 11
BP 1307
EP 1310
DI 10.1586/14787210.2014.966084
PG 4
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA AR8BC
UT WOS:000343799500001
PM 25301228
ER
PT J
AU Matsuura, K
Watanabe, T
Iijima, S
Murakami, S
Fujiwara, K
Orito, E
Iio, E
Endo, M
Kusakabe, A
Shinkai, N
Miyaki, T
Nojiri, S
Joh, T
Tanaka, Y
AF Matsuura, Kentaro
Watanabe, Tsunamasa
Iijima, Sayuki
Murakami, Shuko
Fujiwara, Kei
Orito, Etsuro
Iio, Etsuko
Endo, Mio
Kusakabe, Atsunori
Shinkai, Noboru
Miyaki, Tomokatsu
Nojiri, Shunsuke
Joh, Takashi
Tanaka, Yasuhito
TI Serum interferon-gamma-inducible protein-10 concentrations and IL28B
genotype associated with responses to pegylated interferon plus
ribavirin with and without telaprevir for chronic hepatitis C
SO HEPATOLOGY RESEARCH
LA English
DT Article
DE hepatitis C; IL28B; interferon; interferon--inducible protein-10;
ribavirin; telaprevir
ID VIRUS-INFECTION; VIROLOGICAL RESPONSE; COMBINATION THERAPY;
GENETIC-VARIATION; SPONTANEOUS CLEARANCE; PREDICTIVE-VALUE; VIRAL
RESPONSE; HCV INFECTION; T-LYMPHOCYTES; CHEMOKINE
AB AimSeveral studies have shown that high pretreatment concentrations of serum interferon--inducible protein-10 (IP-10) are correlated with non-response to pegylated interferon (PEG-IFN) plus ribavirin (RBV) for chronic hepatitis C (CHC). However, there are few reports on their effect on the Asian population.
MethodsWe enrolled 104 Japanese genotype 1 CHC individuals treated with PEG-IFN/RBV and 45 with PEG-IFN/RBV/telaprevir, and evaluated the impact of pretreatment serum IP-10 concentrations on their virological responses.
ResultsThe pretreatment serum IP-10 concentrations were not correlated with IL28B genotype. The receiver-operator curve analysis determined the cut-off value of IP-10 for predicting a sustained virological response (SVR) as 300pg/mL. In multivariate analysis, the IL28B favorable genotype and IP-10 concentration of less than 300pg/mL were independent factors for predicting SVR. In a subgroup of patients with the IL28B favorable genotype, the SVR rate was higher in the patients with IP-10 of less than 300 than in those with 300pg/mL or more, whereas no patient with the IL28B unfavorable genotype and IP-10 of 300pg/mL or more achieved SVR. Among the patients treated with PEG-IFN/RBV/telaprevir, low pretreatment concentrations of serum IP-10 were associated with a very rapid virological response, defined as undetectable HCV RNA at week 2 after the start of therapy.
ConclusionPretreatment serum IP-10 concentrations are associated with treatment efficacy in PEG-IFN/RBV and with early viral kinetics of hepatitis C virus in PEG-IFN/RBV/telaprevir therapy.
C1 [Matsuura, Kentaro; Watanabe, Tsunamasa; Iijima, Sayuki; Murakami, Shuko; Tanaka, Yasuhito] Nagoya City Univ, Dept Virol, Liver Unit, Grad Sch Med Sci, Nagoya, Aichi 4678601, Japan.
[Matsuura, Kentaro; Fujiwara, Kei; Iio, Etsuko; Endo, Mio; Shinkai, Noboru; Miyaki, Tomokatsu; Nojiri, Shunsuke; Joh, Takashi] Nagoya City Univ, Dept Gastroenterol & Metab, Grad Sch Med Sci, Nagoya, Aichi 4678601, Japan.
[Orito, Etsuro; Kusakabe, Atsunori] Nagoya Daini Red Cross Hosp, Div Gastroenterol, Nagoya, Aichi, Japan.
[Matsuura, Kentaro] NIH, Infect Dis & Immunogenet Sect, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA.
RP Tanaka, Y (reprint author), Nagoya City Univ, Dept Virol, Liver Unit, Grad Sch Med Sci,Mizuho Ku, Nagoya, Aichi 4678601, Japan.
EM ytanaka@med.nagoya-cu.ac.jp
FU Ministry of Health, Labour and Welfare of Japan; Ministry of Education,
Culture, Sports, Science and Technology
FX THIS STUDY WAS supported in part by a Grant-in-Aid from the Ministry of
Health, Labour and Welfare of Japan, and a Grant-in-Aid from the
Ministry of Education, Culture, Sports, Science and Technology.
NR 41
TC 5
Z9 5
U1 1
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1386-6346
EI 1872-034X
J9 HEPATOL RES
JI Hepatol. Res.
PD NOV
PY 2014
VL 44
IS 12
BP 1208
EP 1216
DI 10.1111/hepr.12294
PG 9
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA AS2ZR
UT WOS:000344145500006
ER
PT J
AU Zhang, K
Zhu, TN
Gao, DM
Zhang, YM
Zhao, QL
Liu, S
Su, TY
Bernier, M
Zhao, RJ
AF Zhang, Kai
Zhu, Tienian
Gao, Dongmei
Zhang, Yimei
Zhao, Qinglan
Liu, Shuang
Su, Tongyi
Bernier, Michel
Zhao, Ruijing
TI Filamin A expression correlates with proliferation and invasive
properties of human metastatic melanoma tumors: implications for
survival in patients
SO JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
LA English
DT Article
DE Malignant melanoma; FLNa; EGFR; Metastasis; Proliferation
ID GROWTH-FACTOR RECEPTOR; ANDROGEN RECEPTOR; DOWN-REGULATION;
CANCER-THERAPY; MUTATIONS; ROLES; CELLS; PROGRESSION; INHIBITION;
ACTIVATION
AB Filamin A (FLNa) cross-links actin filaments into dynamic orthogonal networks and interacts with binding proteins of diverse cellular functions that are implicated in cell growth and motility regulation. Here, we tested the hypothesis that FLNa plays a role in cancer proliferation and metastasis via the regulation of epidermal growth factor receptor (EGFR) function.
Ectopic expression and knockdown of FLNa in human melanoma cell lines was performed to investigate changes in cellular proliferation, migration and invasion in vitro and tumor growth in a xenograft model in the mouse. The role of FLNa in EGFR expression and signaling was evaluated by Western blot. Immunohistochemistry was performed on histological sections of human melanoma tumors to determine whether an association existed between FLNa and overall survival.
The depletion of FLNa significantly reduced the proliferation, migration and invasion of two melanoma cell lines in vitro and was associated with smaller tumors in a xenograft model in vivo. EGF-induced phosphorylation of EGFR and activation of the Raf-MEK-ERK cascade was negatively affected by the silencing of FLNa both in vitro and in vivo. Cancer patients with low melanoma tumor FLNa expression have improved survival benefit.
These data indicate that enhanced tumorigenesis occurs through increase in EGF-induced EGFR activation in FLNa-expressing melanoma cells and that high FLNa levels are predictors of negative outcome for patients with melanoma tumors.
C1 [Zhang, Kai] Hebei Med Univ, Dept Oncol, Shijiazhuang 050017, Hebei, Peoples R China.
[Zhu, Tienian; Zhao, Ruijing] Hebei Med Univ, Key Lab Immune Mech & Intervent Serious Dis Hebei, Dept Immunol, Shijiazhuang 050017, Hebei, Peoples R China.
[Zhu, Tienian; Gao, Dongmei; Zhang, Yimei; Zhao, Qinglan; Su, Tongyi] Bethune Int Peace Hosp, Dept Med Oncol, Shijiazhuang 050082, Hebei, Peoples R China.
[Liu, Shuang] Bethune Int Peace Hosp, Dept Pathol, Shijiazhuang 050082, Hebei, Peoples R China.
[Bernier, Michel] NIA, Translat Gerontol Branch, NIH, Baltimore, MD 21224 USA.
RP Zhao, RJ (reprint author), Hebei Med Univ, Key Lab Immune Mech & Intervent Serious Dis Hebei, Dept Immunol, Shijiazhuang 050017, Hebei, Peoples R China.
EM zhutienian@medmail.com.cn; 6810c@163.com
OI Bernier, Michel/0000-0002-5948-368X
FU National Natural Science Foundation of China [81071846]; Natural Science
Foundation of Hebei Province of China [H2013505059]; Department of
Science and Technology of Hebei Province of China [12396107D]; Wu
Jieping Foundation [320.6750.12604]; Intramural Research Program of
National Institutes of Health, National Institute on Aging
FX This work was supported by the National Natural Science Foundation of
China (No. 81071846, to T.N.Z); Natural Science Foundation of Hebei
Province of China (No. H2013505059, to T.N.Z); Department of Science and
Technology of Hebei Province of China (No. 12396107D, to R.J.Z); Wu
Jieping Foundation (No. 320.6750.12604, to T.N.Z) and, in part, by the
Intramural Research Program of National Institutes of Health, National
Institute on Aging.
NR 49
TC 11
Z9 11
U1 0
U2 3
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0171-5216
EI 1432-1335
J9 J CANCER RES CLIN
JI J. Cancer Res. Clin. Oncol.
PD NOV
PY 2014
VL 140
IS 11
BP 1913
EP 1926
DI 10.1007/s00432-014-1722-3
PG 14
WC Oncology
SC Oncology
GA AR8IT
UT WOS:000343819500012
PM 24908328
ER
PT J
AU Chapa, DW
Akintade, B
Schron, E
Friedmann, E
Thomas, SA
AF Chapa, Deborah W.
Akintade, Bimbola
Schron, Eleanor
Friedmann, Erika
Thomas, Sue A.
TI Is Health-Related Quality of Life a Predictor of Hospitalization or
Mortality Among Women or Men With Atrial Fibrillation?
SO JOURNAL OF CARDIOVASCULAR NURSING
LA English
DT Article
DE arrhythmia; QLI-CV; quality of life; SF-36
ID GENDER-RELATED DIFFERENCES; HEART-FAILURE PATIENTS; RISK-FACTORS; RHYTHM
MANAGEMENT; FOLLOW-UP; CARDIOVASCULAR HEALTH; STROKE PREVENTION; FLUTTER
PATIENTS; SEX-DIFFERENCES; UNITED-STATES
AB Background: Little is known about predictors of mortality or hospitalization in women compared with men in patients with atrial fibrillation (AF). Although there are established gender differences in patients with coronary artery disease (CAD), differences have not been established in AF. Objectives: The aim of this study was to examine clinical and health-related quality of life (HRQOL) predictors of mortality and 1-year hospitalization in women compared with men with AF. Methods: Limited-use data from the National Institutes of Health/National Heart, Lung, and Blood Institute Atrial Fibrillation Follow-up Investigation of Rhythm Management clinical trial provided the sample of 693 patients with AF, 262 women and 431 men. Clinical predictors examined were heart failure (HF), CAD, left ventricular ejection fraction, diabetes, stroke, and age. Predictors of HRQOL included overall HRQOL (Medical Outcomes Study Short Form-36 physical [PCS] and mental component scores) and cardiovascular HRQOL using Quality of Life Index-Cardiac Version. Results: Mortality did not differ (women, 11.4%; men, 14.5%; chi(2)(1) = 0.437, P = .509) according to gender, with mean 3.5-year follow-up. Different variables independently predicted mortality for women and men. For women, diabetes (hazard ratio [HR], 3.415; P = .003), HF (HR, 2.346; P = .027), stroke (HR, 2.41; P = .032), and age (HR, 1.117; P = .002), and for men, CAD (HR, 1.914; P = 02), age (HR, 1.103, P = < .001), worse PCS (HR, 1.089, P = .001), and worse Quality of Life Index-Cardiac Version score (HR, 1.402, P = .025) independently predicted mortality. One-year hospitalization (women, 38.9%; men, 36.4%) did not differ by gender (chi(2)(1) = 0.914, P = .339). Different variables independently predicted 1-year hospitalization-for women: diabetes (odds ratio [OR], 2.359; P = .022), worse PCS (OR, 1.070; P = .003), and rhythm control trial arm (OR, 2.111; P = .006); for men: HF (OR, 2.072; P = .007), worse PCS (OR, 1.045; P = .019), living alone (OR, 1.913; P = .036), and rhythm control trial arm (OR, 2.113; P < .001). Conclusion: Only clinical status predicted mortality among women; HRQOL and clinical status predicted mortality among men. Both clinical and HRQOL variables predicted hospitalization for women and men. Increased monitoring of HRQOL and interventions designed to target the clinical and HRQOL predictors could impact mortality and hospitalization. Nursing interventions may prove effective for modifying most of the predictors of mortality and hospitalization for women and men with AF.
C1 [Chapa, Deborah W.] George Washington Univ, Sch Nursing, Washington, DC 20036 USA.
[Akintade, Bimbola; Friedmann, Erika; Thomas, Sue A.] Univ Maryland, Sch Nursing, Baltimore, MD 21201 USA.
[Schron, Eleanor] NEI, Vis Res Program, Div Extramural Res, NIH, Bethesda, MD 20892 USA.
RP Chapa, DW (reprint author), George Washington Univ, Sch Nursing, 2030 M St NW,Suite 300, Washington, DC 20036 USA.
EM dchapa@gwu.edu
OI Friedmann, Erika/0000-0003-2924-0449
FU National Heart, Lung, and Blood Institute (NHLBI)
FX The Atrial Fibrillation Follow-up Investigation of Rhythm Management
(AFFIRM) is conducted and supported by the National Heart, Lung, and
Blood Institute (NHLBI) in collaboration with the AFFIRM Investigators.
NR 40
TC 2
Z9 2
U1 2
U2 6
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0889-4655
EI 1550-5049
J9 J CARDIOVASC NURS
JI J. Cardiovasc. Nurs.
PD NOV-DEC
PY 2014
VL 29
IS 6
BP 555
EP 564
DI 10.1097/JCN.0000000000000095
PG 10
WC Cardiac & Cardiovascular Systems; Nursing
SC Cardiovascular System & Cardiology; Nursing
GA AR7PP
UT WOS:000343772100013
PM 24165699
ER
PT J
AU Chen, YC
Cobleu, JB
Deziel, NC
Ji, BT
Xue, SZ
Lu, W
Stewart, PA
Friesen, MC
AF Chen, Yu-Cheng
Cobleu, Joseph B.
Deziel, Nicole C.
Ji, Bu-Tian
Xue, Shouzheng
Lu, Wei
Stewart, Patricia A.
Friesen, Melissa C.
TI Reliability and validity of expert assessment based on airborne and
urinary measures of nickel and chromium exposure in the electroplating
industry
SO JOURNAL OF EXPOSURE SCIENCE AND ENVIRONMENTAL EPIDEMIOLOGY
LA English
DT Article
DE expert assessment; reliability; validity; nickel; chromium;
electroplating industry
ID MATERNAL OCCUPATIONAL EXPOSURES; INTERRATER AGREEMENT; RETROSPECTIVE
ASSESSMENT; SUBJECTIVE ASSESSMENT; DERMAL EXPOSURE; POPULATION;
CARCINOGENS; WORKERS; LEAD; VALIDATION
AB The reliability and validity of six experts' exposure ratings were evaluated for 64 nickel-exposed and 72 chromium-exposed workers from six Shanghai electroplating plants based on airborne and urinary nickel and chromium measurements. Three industrial hygienists and three occupational physicians independently ranked the exposure intensity of each metal on an ordinal scale (1-4) for each worker's job in two rounds: the first round was based on responses to an occupational history questionnaire and the second round also included responses to an electroplating industry-specific questionnaire. The Spearman correlation (r(s)) Was used to compare each rating's validity to its corresponding subject-specific arithmetic mean of four airborne or four urinary measurements. Reliability was moderately high (weighted kappa range = 0.60-0.64). Validity was poor to moderate (r(s) = -0.37-0.46) for both airborne and urinary concentrations of both metals. For airborne nickel concentrations, validity differed by plant. For dichotomized metrics, sensitivity and specificity were higher based on urinary measurements (47-78%) than airborne measurements (16-50%). Few patterns were observed by metal, assessment round, or expert type. These results suggest that, for electroplating exposures, experts can achieve moderately high agreement and (reasonably) distinguish between low and high exposures when reviewing responses to in-depth questionnaires used in population-based case-control studies.
C1 [Chen, Yu-Cheng; Cobleu, Joseph B.; Deziel, Nicole C.; Ji, Bu-Tian; Xue, Shouzheng; Friesen, Melissa C.] NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Cobleu, Joseph B.] NCI, Annapolis, MD USA.
[Lu, Wei] Shanghai Municipal Ctr Dis Control, Shanghai, Peoples R China.
[Stewart, Patricia A.] NCI, Arlington, VA USA.
[Stewart, Patricia A.] Stewart Exposure Assessments LLC, Arlington, VA USA.
RP Friesen, MC (reprint author), NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, 9609 Med Ctr Dr,Room 6E608, Bethesda, MD 20892 USA.
EM friesenmc@mail.nih.gov
RI Friesen, Melissa/A-5362-2009
FU Intramural Research Program of the Division of Cancer Epidemiology and
Genetics, National Cancer Institute, National Institutes of Health
FX This study was funded by the Intramural Research Program of the Division
of Cancer Epidemiology and Genetics, National Cancer Institute, National
Institutes of Health.
NR 49
TC 3
Z9 3
U1 1
U2 20
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1559-0631
EI 1559-064X
J9 J EXPO SCI ENV EPID
JI J. Expo. Sci. Environ. Epidemiol.
PD NOV-DEC
PY 2014
VL 24
IS 6
BP 622
EP 628
DI 10.1038/jes.2014.22
PG 7
WC Environmental Sciences; Public, Environmental & Occupational Health;
Toxicology
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health; Toxicology
GA AS0IJ
UT WOS:000343960800011
PM 24736099
ER
PT J
AU O'Brien, TR
Prokunina-Olsson, L
Donnelly, RP
AF O'Brien, Thomas R.
Prokunina-Olsson, Ludmila
Donnelly, Raymond P.
TI IFN-lambda 4: The Paradoxical New Member of the Interferon Lambda Family
SO JOURNAL OF INTERFERON AND CYTOKINE RESEARCH
LA English
DT Review
ID HEPATITIS-C VIRUS; GENOME-WIDE ASSOCIATION; GENETIC-VARIATION;
SPONTANEOUS CLEARANCE; SIGNAL-TRANSDUCTION; ANTIVIRAL ACTIVITY;
RIBAVIRIN THERAPY; HUMAN HEPATOCYTES; STIMULATED GENES; INTERLEUKIN 28B
AB Interferons (IFNs) are generally considered antiviral cytokines, yet the newly discovered IFN-lambda 4 is linked with the failure to clear hepatitis C virus (HCV) infection either spontaneously or in response to treatment. IFN-lambda 4 can be generated only by individuals who carry the IFNL4-Delta G allele (rs368234815), which is the strongest known host factor for predicting clearance of HCV. The ancestral IFNL4-Delta G allele is the major variant in Africans while the minor variant in Asians, suggesting very strong negative genetic selection for this allele-most likely driven by an infectious agent other than HCV. IFN-lambda 4 most closely resembles IFN-lambda 3, but these proteins share only 29% amino-acid identity, and, in contrast to IFN-lambda 3, IFN-lambda 4 is only weakly secreted. Nevertheless, IFN-lambda 4 signals through the IFN-lambda receptor complex and induces expression of IFN-stimulated genes via the Janus kinase-signal transducer and activator of transcription signaling pathway. Although the IFNL4-Delta G variant is strongly associated with the failure to clear HCV infection, HCV-infected patients who carry this allele have lower baseline HCV RNA levels in the absence of treatment. Resolving the paradoxical functions of IFN-lambda 4, which appears to induce antiviral activity yet impair effective clearance of HCV, may yield critical new insights into the immunologic response to HCV infection and IFN biology.
C1 [O'Brien, Thomas R.] NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Prokunina-Olsson, Ludmila] NCI, Lab Translat Genom, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Donnelly, Raymond P.] US FDA, Div Therapeut Prot, Ctr Drug Evaluat & Res, Bethesda, MD 20014 USA.
RP O'Brien, TR (reprint author), NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, 9609 Med Ctr Dr,6E108 MSC 9767, Bethesda, MD 20892 USA.
EM obrient@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. The content of this publication does
not necessarily reflect the views or policies of the Department of
Health and Human Services, nor does the mention of trade names,
commercial products, or organizations imply endorsement by the U.S.
Government.
NR 60
TC 36
Z9 37
U1 2
U2 10
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1079-9907
EI 1557-7465
J9 J INTERF CYTOK RES
JI J. Interferon Cytokine Res.
PD NOV 1
PY 2014
VL 34
IS 11
BP 829
EP 838
DI 10.1089/jir.2013.0136
PG 10
WC Biochemistry & Molecular Biology; Cell Biology; Immunology
SC Biochemistry & Molecular Biology; Cell Biology; Immunology
GA AS3EI
UT WOS:000344158900001
PM 24786669
ER
PT J
AU Meager, A
Heath, A
Dilger, P
Zoon, K
Wadhwa, M
AF Meager, Anthony
Heath, Alan
Dilger, Paula
Zoon, Kathryn
Wadhwa, Meenu
CA Participants Collaborative Study
TI Standardization of Human IL-29 (IFN-lambda 1): Establishment of a World
Health Organization International Reference Reagent for IL-29
(IFN-lambda 1)
SO JOURNAL OF INTERFERON AND CYTOKINE RESEARCH
LA English
DT Article
ID INTERFERON-LAMBDA 1; HEPATITIS-C; I INTERFERONS; INFECTION;
KERATINOCYTES; EXPRESSION; GENETICS; COMPLEX; FAMILY; CELLS
AB Human interleukin-29 (IL-29), a helical cytokine with interferon-like activities, is currently being developed as a clinical biotherapeutic to treat chronic hepatitis C infection and some cancers. As such, the World Health Organization (WHO) has recognized a need for biological standardization of IL-29 and the establishment of an internationally available reference reagent of IL-29. In order to accomplish this, an international collaborative study that evaluates WHO candidate reference reagents of IL-29 was instigated by the National Institute for Biological Standards and Control (NIBSC) in 2010 and was carried out in the succeeding year. Two preparations of human sequence recombinant IL-29, one expressed in murine NS0 cells and the other in Escherichia coli, were formulated and lyophilized at NIBSC before evaluation in the collaborative study for their suitability to serve as a reference reagent. The preparations were tested by 6 laboratories from 4 countries using in vitro bioassays and also evaluated for thermal stability within the NIBSC laboratory. On the basis of the results of the collaborative study, both preparations, 07/212 (NS0-derived) and 10/176 (E. coli-derived) were judged sufficiently active and stable to serve as a reference reagent. However, since IL-29 produced in E. coli is in development for clinical applications, it was recommended that the preparation coded 10/176 be established as the WHO international reference reagent for human IL-29. This recommendation was accepted, and the IL-29 preparation coded 10/176 was formally established by the WHO ECBS at its meeting in October 2012 as the WHO international reference reagent for IL-29 with an assigned unitage of 5,000 reference units per ampoule.
C1 [Meager, Anthony; Dilger, Paula; Wadhwa, Meenu] NIBSC, Med & Healthcare Prod Regulatory Agcy, Cytokine & Growth Factors Sect, Biotherapeut Grp, Potters Bar EN6 3QG, Herts, England.
[Heath, Alan] NIBSC, Med & Healthcare Prod Regulatory Agcy, Biostat Sect, Potters Bar EN6 3QG, Herts, England.
[Zoon, Kathryn] NIAID, Div Intramural Res, NIH, Bethesda, MD 20892 USA.
RP Wadhwa, M (reprint author), NIBSC, Med & Healthcare Prod Regulatory Agcy, Cytokine & Growth Factors Sect, Biotherapeut Grp, Blanche Lane, Potters Bar EN6 3QG, Herts, England.
EM meenu.wadhwa@nibsc.org
NR 26
TC 2
Z9 2
U1 0
U2 0
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1079-9907
EI 1557-7465
J9 J INTERF CYTOK RES
JI J. Interferon Cytokine Res.
PD NOV 1
PY 2014
VL 34
IS 11
BP 876
EP 884
DI 10.1089/jir.2014.0015
PG 9
WC Biochemistry & Molecular Biology; Cell Biology; Immunology
SC Biochemistry & Molecular Biology; Cell Biology; Immunology
GA AS3EI
UT WOS:000344158900006
PM 24955567
ER
PT J
AU Dao, L
Lucotte, B
Glancy, B
Chang, LC
Hsu, LY
Balaban, RS
AF Dao, L.
Lucotte, B.
Glancy, B.
Chang, L. -C.
Hsu, L. -Y.
Balaban, R. S.
TI Use of independent component analysis to improve signal-to-noise ratio
in multi-probe fluorescence microscopy
SO JOURNAL OF MICROSCOPY
LA English
DT Article
DE ANEPPS; enhanced signal to noise; NAD(P)H; skeletal muscle; total
emission detection; vascular imaging
ID IN-VIVO; OPTICAL MICROSCOPY; ALGORITHMS; SEPARATION; IMAGES
AB In conventional multi-probe fluorescence microscopy, narrow bandwidth filters on detectors are used to avoid bleed-through artefacts between probes. The limited bandwidth reduces the signal-to-noise ratio of the detection, often severely compromising one or more channels. Herein, we describe a process of using independent component analysis to discriminate the position of different probes using only a dichroic mirror to differentiate the signals directed to the detectors. Independent component analysis was particularly effective in samples where the spatial overlap between the probes is minimal, a very common case in cellular microscopy. This imaging scheme collects nearly all of the emitted light, significantly improving the image signal-to-noise ratio. In this study, we focused on the detection of two fluorescence probes used in vivo, NAD(P)H and ANEPPS. The optimal dichroic mirror cutoff frequency was determined with simulations using the probes spectral emissions. A quality factor, defined as the cross-channel contrast-to-noise ratio, was optimized to maximize signals while maintaining spatial discrimination between the probes after independent component analysis post-processing. Simulations indicate that a approximate to 3 fold increase in signal-to-noise ratio using the independent component analysis approach can be achieved over the conventional narrow-band filtering approach without loss of spatial discrimination. We confirmed this predicted performance from experimental imaging of NAD(P)H and ANEPPS in mouse skeletal muscle, in vivo. For many multi-probe studies, the increased sensitivity of this full bandwidth' approach will lead to improved image quality and/or reduced excitation power requirements.
Lay Description Signal to noise ratio (SNR) is a limiting factor in many fluorescence microscopy techniques to image multiple fluorescence probes simultaneously. Conventional approaches using band-pass filters to minimize cross-talk between channels can significantly reduce SNR by limiting the number of emitted photons that are detected. Using the assumption that the fluorescent probes are not present in the same regions of the cell or tissue, a common feature for many but not all probes, a technique is presented where most of the emitted light is collected and then discriminated using Independent Component Analysis. To illustrate this approach increased the SNR by a factor of approximate to 3 over the conventional filter scheme in the skeletal muscle of a live mouse. This improvement in SNR can be used to improve image quality or decrease the power and time required to collect a fluorescent image if the probes are spatially distinct.
C1 [Dao, L.; Lucotte, B.; Glancy, B.; Hsu, L. -Y.; Balaban, R. S.] NHLBI, Cardiac Energet Lab, NIH, Bethesda, MD 20892 USA.
[Dao, L.; Chang, L. -C.] Catholic Univ Amer, Dept Elect Engn & Comp Sci, Washington, DC 20064 USA.
RP Balaban, RS (reprint author), NHLBI, Cardiac Energet Lab, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM rsb@nih.gov
RI Glancy, Brian/P-3163-2016
OI Glancy, Brian/0000-0002-8571-244X
FU Intramural NIH HHS [ZIA HL004610-07]
NR 19
TC 1
Z9 1
U1 3
U2 10
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0022-2720
EI 1365-2818
J9 J MICROSC-OXFORD
JI J. Microsc..
PD NOV
PY 2014
VL 256
IS 2
BP 133
EP 144
DI 10.1111/jmi.12167
PG 12
WC Microscopy
SC Microscopy
GA AR8EA
UT WOS:000343807300008
PM 25159193
ER
PT J
AU Xi, L
Pham, TH
Rosenberg, SA
Raffeld, M
AF Xi, L.
Pham, T. H.
Rosenberg, S. A.
Raffeld, M.
TI Circulating Tumor DNA as an Indicator of Response to Tumor-Infiltrating
Lymphocyte Immunotherapy in Malignant Melanoma
SO JOURNAL OF MOLECULAR DIAGNOSTICS
LA English
DT Meeting Abstract
CT Annual Meeting of the Association-for-Molecular-Pathology (AMP)
CY NOV 12-15, 2014
CL National Harbor, MD
SP Assoc Mol Pathol
C1 [Xi, L.; Pham, T. H.; Rosenberg, S. A.; Raffeld, M.] NCI, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1525-1578
EI 1943-7811
J9 J MOL DIAGN
JI J. Mol. Diagn.
PD NOV
PY 2014
VL 16
IS 6
MA ST18
BP 749
EP 749
PG 1
WC Pathology
SC Pathology
GA AR7YZ
UT WOS:000343794200234
ER
PT J
AU Harrington, R
Datta, V
Camalier, C
Walsh, W
Sims, D
Das, B
Lih, C
Williams, P
AF Harrington, R.
Datta, V.
Camalier, C.
Walsh, W.
Sims, D.
Das, B.
Lih, C.
Williams, P.
TI Comparison of Spectrophotometry and qPCR for Determining DNA
Concentration from FFPE Samples for Next-Generation Sequencing Assay
SO JOURNAL OF MOLECULAR DIAGNOSTICS
LA English
DT Meeting Abstract
CT Annual Meeting of the Association-for-Molecular-Pathology (AMP)
CY NOV 12-15, 2014
CL National Harbor, MD
SP Assoc Mol Pathol
C1 [Harrington, R.; Datta, V.; Camalier, C.; Walsh, W.; Sims, D.; Das, B.; Lih, C.; Williams, P.] Leidos Biomed Res, Frederick, MD USA.
[Harrington, R.; Datta, V.] NCI, Frederick, MD USA.
NR 0
TC 1
Z9 1
U1 2
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1525-1578
EI 1943-7811
J9 J MOL DIAGN
JI J. Mol. Diagn.
PD NOV
PY 2014
VL 16
IS 6
MA TT06
BP 773
EP 773
PG 1
WC Pathology
SC Pathology
GA AR7YZ
UT WOS:000343794200336
ER
PT J
AU Iriki, H
Adachi, T
Mori, M
Tanese, K
Funakoshi, T
Karigane, D
Shimizu, T
Okamoto, S
Nagao, K
AF Iriki, Hisato
Adachi, Takeya
Mori, Mariko
Tanese, Keiji
Funakoshi, Takeru
Karigane, Daiki
Shimizu, Takayuki
Okamoto, Shinichiro
Nagao, Keisuke
TI Toxic epidermal necrolysis in the absence of circulating T cells: A
possible role for resident memory T cells
SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY
LA English
DT Letter
ID SKIN
C1 [Iriki, Hisato; Adachi, Takeya; Mori, Mariko; Tanese, Keiji; Funakoshi, Takeru; Nagao, Keisuke] Keio Univ, Sch Med, Dept Dermatol, Tokyo, Japan.
[Karigane, Daiki; Shimizu, Takayuki; Okamoto, Shinichiro] Keio Univ, Sch Med, Dept Hematol, Tokyo, Japan.
RP Nagao, K (reprint author), NCI, Dermatol Branch, Ctr Canc Res, NIH, Bldg 10,Rm 12N238,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM keisuke.nagao@nih.gov
RI Nagao, Keisuke/J-5116-2013; Funakoshi, Takeru/A-7994-2015
OI Nagao, Keisuke/0000-0002-7005-3138; Funakoshi,
Takeru/0000-0002-8893-4590
NR 5
TC 0
Z9 0
U1 0
U2 2
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0190-9622
J9 J AM ACAD DERMATOL
JI J. Am. Acad. Dermatol.
PD NOV
PY 2014
VL 71
IS 5
BP E214
EP E216
DI 10.1016/j.jaad.2014.07.013
PG 4
WC Dermatology
SC Dermatology
GA AR9TD
UT WOS:000343918200021
PM 25437999
ER
PT J
AU Margolis, R
Derr, L
Dunn, M
Huerta, M
Larkin, J
Sheehan, J
Guyer, M
Green, ED
AF Margolis, Ronald
Derr, Leslie
Dunn, Michelle
Huerta, Michael
Larkin, Jennie
Sheehan, Jerry
Guyer, Mark
Green, Eric D.
TI The National Institutes of Health's Big Data to Knowledge (BD2K)
initiative: capitalizing on biomedical big data
SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION
LA English
DT Article
AB Biomedical research has and will continue to generate large amounts of data (termed 'big data') in many formats and at all levels. Consequently, there is an increasing need to better understand and mine the data to further knowledge and foster new discovery. The National Institutes of Health (NIH) has initiated a Big Data to Knowledge (BD2K) initiative to maximize the use of biomedical big data. BD2K seeks to better define how to extract value from the data, both for the individual investigator and the overall research community, create the analytic tools needed to enhance utility of the data, provide the next generation of trained personnel, and develop data science concepts and tools that can be made available to all stakeholders.
C1 [Margolis, Ronald] NIDDK, NIH, Bethesda, MD 20892 USA.
[Derr, Leslie] NIH, Off Director, Bethesda, MD 20892 USA.
[Dunn, Michelle] NCI, NIH, Bethesda, MD 20892 USA.
[Huerta, Michael; Sheehan, Jerry] NIH, Natl Lib Med, Bethesda, MD 20892 USA.
[Larkin, Jennie] NHLBI, NIH, Bethesda, MD 20892 USA.
[Guyer, Mark; Green, Eric D.] NHGRI, NIH, Bethesda, MD 20892 USA.
RP Margolis, R (reprint author), NIDDK, NIH, 6707 Democracy Blvd,Room 693, Bethesda, MD 20892 USA.
EM margolisr@mail.nih.gov
OI Margolis, Ronald/0000-0002-8956-0455
NR 2
TC 44
Z9 47
U1 14
U2 101
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 1067-5027
EI 1527-974X
J9 J AM MED INFORM ASSN
JI J. Am. Med. Inf. Assoc.
PD NOV
PY 2014
VL 21
IS 6
BP 957
EP 958
DI 10.1136/amiajnl-2014-002974
PG 2
WC Computer Science, Information Systems; Computer Science,
Interdisciplinary Applications; Health Care Sciences & Services;
Information Science & Library Science; Medical Informatics
SC Computer Science; Health Care Sciences & Services; Information Science &
Library Science; Medical Informatics
GA AR7RJ
UT WOS:000343776700003
PM 25008006
ER
PT J
AU Cudkowicz, ME
Titus, S
Kearney, M
Yu, H
Sherman, A
Schoenfeld, D
Hayden, D
Shui, A
Brooks, B
Conwit, R
Felsenstein, D
Greenblatt, DJ
Keroack, M
Kissel, JT
Miller, R
Rosenfeld, J
Rothstein, JD
Simpson, E
Tolkoff-Rubin, N
Zinman, L
Shefner, JM
AF Cudkowicz, Merit E.
Titus, Sarah
Kearney, Marianne
Yu, Hong
Sherman, Alexander
Schoenfeld, David
Hayden, Douglas
Shui, Amy
Brooks, Benjamin
Conwit, Robin
Felsenstein, Donna
Greenblatt, David J.
Keroack, Myles
Kissel, John T.
Miller, Robert
Rosenfeld, Jeffrey
Rothstein, Jeffrey D.
Simpson, Ericka
Tolkoff-Rubin, Nina
Zinman, Lorne
Shefner, Jeremy M.
CA Ceftriaxone Study Investigators
TI Safety and efficacy of ceftriaxone for amyotrophic lateral sclerosis: a
multi-stage, randomised, double-blind, placebo-controlled trial
SO LANCET NEUROLOGY
LA English
DT Article
ID CEREBROSPINAL-FLUID; NERVOUS-SYSTEM; ALS; GLUTAMATE; RILUZOLE;
INFECTIONS; EXPRESSION; SURVIVAL; MODELS; STROKE
AB Background Glutamate excitotoxicity might contribute to the pathophysiology of amyotrophic lateral sclerosis. In animal models, decreased excitatory aminoacid transporter 2 (EAAT2) overexpression delays disease onset and prolongs survival, and ceftriaxone increases EAAT2 activity We aimed to assess the safety and efficacy of ceftriaxone for amyotrophic lateral sclerosis in a combined phase 1, 2, and 3 clinical trial.
Methods This three-stage randomised, double-blind, placebo-controlled study was done at 59 clinical sites in the USA and Canada between Sept 4, 2006, and July 30, 2012. Eligible adult patients had amyotrophic lateral sclerosis, a vital capacity of more than 60% of that predicted for age and height, and symptom duration of less than 3 years. In stages 1 (pharmacokinetics) and 2 (safety), participants were randomly allocated (2:1) to ceftriaxone (2 g or 4 g per day) or placebo. In stage 3 (efficacy), participants assigned to ceftriaxone in stage 2 received 4 g ceftriaxone, participants assigned to placebo in stage 2 received placebo, and new participants were randomly assigned (2:1) to 4 g ceftriaxone or placebo. Participants, family members, and site staff were masked to treatment assignment. Randomisation was done by a computerised randomisation sequence with permuted blocks of 3. Participants received 2 g ceftriaxone or placebo twice daily through a central venous catheter administered at home by a trained caregiver. To minimise biliary side-effects, participants assigned to ceftriaxone also received 300 mg ursodeoxycholic acid twice daily and those assigned to placebo received matched placebo capsules. The coprimary efficacy outcomes were survival and functional decline, measured as the slope of Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) scores. Analyses were by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00349622.
Findings Stage 3 included 66 participants from stages 1 and 2 and 448 new participants. In total, 340 participants were randomly allocated to ceftriaxone and 173 to placebo. During stages 1 and 2, mean ALSFRS-R declined more slowly in participants who received 4 g ceftriaxone than in those on placebo (difference 0.51 units per month, 95% CI 0.02 to 1. 00; P=0.0416), but in stage 3 functional decline between the treatment groups did not differ (0.09, 0-06 to 024; p=0.2370). No significant differences in survival between the groups were recorded in singe 3 (HR 0.90, 95% CI 0-71 to 1-15; p=0.4146). Gastrointestinal adverse events and hepatobiliary adverse events were more common in the ceftriaxone group than in the placebo group (gastrointestinal, 245 of 340 [72%] ceftriaxone vs 97 of 173 [56%] placebo, p=0. 0004; hepatobiliary, 211 [62%] vs 19 [11%], p<0.0001). Significantly more participants who received ceftriaxone had serious hepatobiliary serious adverse events (41 participants [12%]) than did those who received placebo (0 participants).
Interpretation Despite promising stage 2 data, stage 3 of this trial of ceftriaxone in amyotrophic lateral sclerosis did not show clinical efficacy. The adaptive design allowed for seamless transition from one phase to another, and central venous catheter use in the home setting was shown to be feasible.
C1 [Cudkowicz, Merit E.; Titus, Sarah; Kearney, Marianne; Yu, Hong; Sherman, Alexander; Schoenfeld, David; Hayden, Douglas; Shui, Amy; Felsenstein, Donna; Tolkoff-Rubin, Nina] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Brooks, Benjamin] Carolinas Med Ctr, Charlotte, NC 28203 USA.
[Conwit, Robin] NINDS, Bethesda, MD 20892 USA.
[Greenblatt, David J.] Tufts Univ, Sch Med, Boston, MA 02111 USA.
[Keroack, Myles] Eliot Hlth Syst, Manchester, NH USA.
[Kissel, John T.] Ohio State Univ, Columbus, OH 43210 USA.
[Miller, Robert] Calif Pacific Med Ctr, San Francisco, CA USA.
[Rosenfeld, Jeffrey] Univ Calif San Francisco, Fresno, CA USA.
[Rothstein, Jeffrey D.] Johns Hopkins Univ, Baltimore, MD USA.
[Simpson, Ericka] Methodist Hosp, Houston, TX 77030 USA.
[Zinman, Lorne] Sunnybrook Hlth Sci Ctr, Toronto, ON M4N 3M5, Canada.
[Shefner, Jeremy M.] SUNY Upstate Med Univ, Syracuse, NY 13210 USA.
RP Cudkowicz, ME (reprint author), Neurol Clin Res Inst, 165 Cambridge St,Floor 6, Boston, MA 02114 USA.
EM mcudkowicz@partners.org
OI Caress, James/0000-0002-5814-6083
FU National Institute of Neurological Disorders and Stroke
FX National Institute of Neurological Disorders and Stroke.
NR 42
TC 22
Z9 22
U1 1
U2 9
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1474-4422
EI 1474-4465
J9 LANCET NEUROL
JI Lancet Neurol.
PD NOV
PY 2014
VL 13
IS 11
BP 1083
EP 1091
DI 10.1016/S1474-4422(14)70222-4
PG 9
WC Clinical Neurology
SC Neurosciences & Neurology
GA AR7TZ
UT WOS:000343783900015
PM 25297012
ER
PT J
AU Jiang, X
Lu, HB
Shigeno, S
Tan, LH
Yang, YH
Ragsdale, CW
Gao, JH
AF Jiang, Xia
Lu, Hanbing
Shigeno, Shuichi
Tan, Li-Hai
Yang, Yihong
Ragsdale, Clifton W.
Gao, Jia-Hong
TI Octopus Visual System: A Functional MRI Model for Detecting Neuronal
Electric Currents without a Blood-Oxygen-Level-Dependent Confound
SO MAGNETIC RESONANCE IN MEDICINE
LA English
DT Article
DE functional MRI; retina; optic lobe; electroretinogram; local field
potential; cephalopod
ID MAGNETIC-RESONANCE; IN-VIVO; BRAIN; FIELDS; SIGNAL; NERVE; BOLD; FMRI;
ELECTRORETINOGRAM; SPECTROSCOPY
AB PurposeDespite the efforts that have been devoted to detecting the transient magnetic fields generated by neuronal firing, the conclusion that a functionally relevant signal can be measured with MRI is still controversial. For human studies of neuronal current MRI (nc-MRI), the blood-oxygen-level-dependent (BOLD) effect remains an irresolvable confound. For tissue studies where hemoglobin is removed, natural sensory stimulation is not possible. This study investigates the feasibility of detecting a physiologically induced nc-MRI signal in vivo in a BOLD-free environment.
MethodsThe cephalopod mollusc Octopus bimaculoides has vertebrate-like eyes, large optic lobes (OLs), and blood that does not contain hemoglobin. Visually evoked potentials were measured in the octopus retina and OL by electroretinogram and local field potential. nc-MRI scans were conducted at 9.4 Tesla to capture these activities.
ResultsElectrophysiological recording detected strong responses in the retina and OL in vivo; however, nc-MRI failed to demonstrate any statistically significant signal change with a detection threshold of 0.2 degrees for phase and 0.2% for magnitude. Experiments in a dissected eye-OL preparation yielded similar results.
ConclusionThese findings in a large hemoglobin-free nervous system suggest that sensory evoked neuronal magnetic fields are too weak for direct detection with current MRI technology. Magn Reson Med 72:1311-1319, 2014. (c) 2013 Wiley Periodicals, Inc.
C1 [Jiang, Xia] Univ Chicago, Brain Res Imaging Ctr, Chicago, IL 60637 USA.
[Jiang, Xia] Univ Chicago, Dept Radiol, Chicago, IL 60637 USA.
[Lu, Hanbing; Yang, Yihong] NIDA, NIH, Baltimore, MD USA.
[Shigeno, Shuichi; Ragsdale, Clifton W.] Univ Chicago, Dept Neurobiol, Chicago, IL 60637 USA.
[Tan, Li-Hai] Univ Hong Kong, State Key Lab Brain Res, Hong Kong, Hong Kong, Peoples R China.
[Gao, Jia-Hong] Peking Univ, McGovern Inst Brain Res, Beijing City Key Lab Med Phys & Engn, Ctr MRI Res, Beijing 100871, Peoples R China.
RP Gao, JH (reprint author), Peking Univ, Ctr MRI Res, 5 Yiheyuan Rd, Beijing 100871, Peoples R China.
EM jgao@pku.edu.cn
FU NIH [RO1EB015023, R21EB004753]; NSF [IOS-1021909]; China national
strategic basic research 973 program [2012CB720701]
FX Grant sponsor: NIH; Grant numbers: RO1EB015023; R21EB004753; Grant
sponsor: NSF; Grant number: IOS-1021909; Grant sponsor: China national
strategic basic research 973 program; Grant number: 2012CB720701.
NR 47
TC 3
Z9 3
U1 4
U2 14
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0740-3194
EI 1522-2594
J9 MAGN RESON MED
JI Magn. Reson. Med.
PD NOV
PY 2014
VL 72
IS 5
BP 1311
EP 1319
DI 10.1002/mrm.25051
PG 9
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA AR9ED
UT WOS:000343873900013
PM 24301336
ER
PT J
AU Root, DH
Mejias-Aponte, CA
Zhang, SL
Wang, HL
Hoffman, AF
Lupica, CR
Morales, M
AF Root, David H.
Mejias-Aponte, Carlos A.
Zhang, Shiliang
Wang, Hui-Ling
Hoffman, Alexander F.
Lupica, Carl R.
Morales, Marisela
TI Single rodent mesohabenular axons release glutamate and GABA
SO NATURE NEUROSCIENCE
LA English
DT Article
ID VENTRAL TEGMENTAL AREA; NEGATIVE REWARD SIGNALS; LATERAL HABENULA;
DOPAMINE NEURONS; PATHWAY; RAT; PROJECTIONS; SYNAPSES; STIMULATION;
POPULATION
AB The lateral habenula (LHb) is involved in reward, aversion, addiction and depression through descending interactions with several brain structures, including the ventral tegmental area (VTA). The VTA provides reciprocal inputs to LHb, but their actions are unclear. Here we show that the majority of rat and mouse VTA neurons innervating LHb coexpress markers for both glutamate signaling (vesicular glutamate transporter 2; VGluT2) and GABA signaling (glutamic acid decarboxylase; GAD, and vesicular GABA transporter; VGaT). A single axon from these mesohabenular neurons coexpresses VGluT2 protein and VGaT protein and, surprisingly, establishes symmetric and asymmetric synapses on LHb neurons. In LHb slices, light activation of mesohabenular fibers expressing channelrhodopsin2 driven by VGluT2 (Slc17a6) or VGaT (Slc32a1) promoters elicits release of both glutamate and GABA onto single LHb neurons. In vivo light activation of mesohabenular terminals inhibits or excites LHb neurons. Our findings reveal an unanticipated type of VTA neuron that cotransmits glutamate and GABA and provides the majority of mesohabenular inputs.
C1 [Root, David H.; Mejias-Aponte, Carlos A.; Zhang, Shiliang; Wang, Hui-Ling; Morales, Marisela] NIDA, Neuronal Networks Sect, Integrat Neurosci Res Branch, Baltimore, MD 21224 USA.
[Hoffman, Alexander F.; Lupica, Carl R.] NIDA, Electrophysiol Res Sect, Cellular Neurobiol Res Branch, Baltimore, MD USA.
RP Morales, M (reprint author), NIDA, Neuronal Networks Sect, Integrat Neurosci Res Branch, Baltimore, MD 21224 USA.
EM mmorales@intra.nida.nih.gov
RI Hoffman, Alexander/H-3035-2012;
OI Hoffman, Alexander/0000-0002-2676-0628; Root, David/0000-0002-1927-2175
FU Intramural Research Program of the National Institute on Drug Abuse, US
National Institutes of Health (IRP/NIDA/NIH)
FX We thank R. Wise, J. Qi and J. Aceves for comments and J. Qi for
assistance with viral injections used in ultrastructural experiments.
Viruses were packaged by the NIDA IRP Optogenetics and Transgenic
Technology Core. The Intramural Research Program of the National
Institute on Drug Abuse, US National Institutes of Health (IRP/NIDA/NIH)
supported this work.
NR 39
TC 55
Z9 56
U1 1
U2 19
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1097-6256
EI 1546-1726
J9 NAT NEUROSCI
JI Nat. Neurosci.
PD NOV
PY 2014
VL 17
IS 11
BP 1543
EP 1551
DI 10.1038/nn.3823
PG 9
WC Neurosciences
SC Neurosciences & Neurology
GA AS0LT
UT WOS:000343969300019
PM 25242304
ER
PT J
AU Kivell, B
Uzelac, Z
Sundaramurthy, S
Rajamanickam, J
Ewald, A
Chefer, V
Jaligam, V
Bolan, E
Simonson, B
Annamalai, B
Mannangatti, P
Prisinzano, TE
Gomes, I
Devi, LA
Jayanthi, LD
Sitte, HH
Ramamoorthy, S
Shippenberg, TS
AF Kivell, Bronwyn
Uzelac, Zeljko
Sundaramurthy, Santhanalakshmi
Rajamanickam, Jeyaganesh
Ewald, Amy
Chefer, Vladimir
Jaligam, Vanaja
Bolan, Elizabeth
Simonson, Bridget
Annamalai, Balasubramaniam
Mannangatti, Padmanabhan
Prisinzano, Thomas E.
Gomes, Ivone
Devi, Lakshmi A.
Jayanthi, Lankupalle D.
Sitte, Harald H.
Ramamoorthy, Sammanda
Shippenberg, Toni S.
TI Salvinorin A regulates dopamine transporter function via a kappa opioid
receptor and ERK1/2-dependent mechanism
SO NEUROPHARMACOLOGY
LA English
DT Article
DE Kappa opioid receptor; Dysphoric; Pro-depressant; Dopamine transporter;
Serotonin transporter; Trafficking; Salvinorin A
ID RESONANCE ENERGY-TRANSFER; PROTEIN-KINASE-C; HUMAN SEROTONIN
TRANSPORTER; NUCLEUS-ACCUMBENS; SURFACE EXPRESSION; NONHUMAN-PRIMATES;
PLACE AVERSION; D-2 RECEPTORS; LIVING CELLS; PHOSPHORYLATION
AB Salvinorin A (SalA), a selective x-opioid receptor (KOR) agonist, produces dysphoria and pro-depressant like effects. These actions have been attributed to inhibition of striatal dopamine release. The dopamine transporter (DAT) regulates dopamine transmission via uptake of released neurotransmitter. KORs are apposed to DAT in dopamine nerve terminals suggesting an additional target by which SalA modulates dopamine transmission. SalA produced a concentration-dependent, nor-binaltorphimine (BNI)- and pertussis toxin-sensitive increase of ASP(+) accumulation in EM4 cells coexpressing myc-KOR and YFP-DAT, using live cell imaging and the fluorescent monoamine transporter substrate, trans 4-(4-(dimethylamino)-styryl)-N-methylpyridinium) (ASP(+)). Other KOR agonists also increased DAT activity that was abolished by BNI pretreatment. While SalA increased DAT activity, SalA treatment decreased serotonin transporter (SERT) activity and had no effect on norepinephrine transporter (NET) activity. In striatum, SalA increased the V-max for DAT mediated DA transport and DAT surface expression. SalA up-regulation of DAT function is mediated by NOR activation and the KOR-linked extracellular signal regulated kinase-1/2 (ERK1/2) pathway. Co-immunoprecipitation and BRET studies revealed that DAT and KOR exist in a complex. In live cells, DAT and KOR exhibited robust FRET signals under basal conditions. SalA exposure caused a rapid and significant increase of the FRET signal. This suggests that the formation of KOR and DAT complexes is promoted in response to KOR activation. Together, these data suggest that enhanced DA transport and decreased DA release resulting in decreased dopamine signalling may contribute to the dysphoric and pro-depressant like effects of SalA and other KOR agonists. (C) 2014 Elsevier Ltd. All rights reserved.
C1 [Kivell, Bronwyn; Ewald, Amy; Simonson, Bridget] Victoria Univ Wellington, Sch Biol Sci, Wellington, New Zealand.
[Uzelac, Zeljko; Sitte, Harald H.] Med Univ Vienna, Inst Pharmacol, Ctr Physiol & Pharmacol, A-1090 Vienna, Austria.
[Sundaramurthy, Santhanalakshmi; Rajamanickam, Jeyaganesh; Mannangatti, Padmanabhan; Jayanthi, Lankupalle D.; Ramamoorthy, Sammanda] Virginia Commonwealth Univ, Dept Pharmacol & Toxicol, Richmond, VA 23298 USA.
[Kivell, Bronwyn; Chefer, Vladimir; Jaligam, Vanaja; Bolan, Elizabeth; Shippenberg, Toni S.] NIDA, Integrat Neurosci Sect, NIH, Intramural Res Program, Baltimore, MD 21224 USA.
[Annamalai, Balasubramaniam] Med Univ S Carolina, Dept Neurosci, Charleston, SC 29425 USA.
[Prisinzano, Thomas E.] Univ Kansas, Dept Med Chem, Lawrence, KS 66045 USA.
[Gomes, Ivone; Devi, Lakshmi A.] Mt Sinai Sch Med, Dept Pharmacol & Syst Therapeut, New York, NY 10029 USA.
RP Ramamoorthy, S (reprint author), Virginia Commonwealth Univ, Dept Pharmacol & Toxicol, R Blackwell Smith Bldg,Room 756A,410 North, Richmond, VA 23298 USA.
EM sramamoorthy@vcu.edu
RI Kivell, Bronwyn/P-3140-2014; Prisinzano, Thomas/B-7877-2010;
OI Kivell, Bronwyn/0000-0001-9699-553X; Simonson,
Bridget/0000-0002-3190-4796; Sitte, Harald/0000-0002-1339-7444
FU National Institutes of Health and National Institute on Drug Abuse
Intramural Research Program; NIH [MH083928, MH091633, DA018151,
DA019521, DA08863, GM071558]; Health Research Council of New Zealand;
Austrian Science Fund/FWF [P23658]
FX This work was supported by the National Institutes of Health and
National Institute on Drug Abuse Intramural Research Program (T.S.S),
NIH grants, MH083928, MH091633 (S.R), DA018151 (T.E.P), DA019521,
DA08863, GM071558 (L.A.D.), The Health Research Council of New Zealand
(B.K) and Austrian Science Fund/FWF, P23658 (H.H.S). CCRP-YFP was kindly
provided by Dr Michel Bouvier (University of Montreal). DAT constructs
were provided by Dr. Jonathan Javitch.
NR 81
TC 14
Z9 14
U1 0
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 NOV
PY 2014
VL 86
BP 228
EP 240
DI 10.1016/j.neuropharm.2014.07.016
PG 13
WC Neurosciences; Pharmacology & Pharmacy
SC Neurosciences & Neurology; Pharmacology & Pharmacy
GA AR8QN
UT WOS:000343839800025
PM 25107591
ER
PT J
AU Techlovska, S
Chambers, JN
Dvorakova, M
Petralia, RS
Wang, YX
Hajkova, A
Nova, A
Frankova, D
Prezeau, L
Blahos, J
AF Techlovska, Sarka
Chambers, Jayne Nicole
Dvorakova, Michaela
Petralia, Ronald S.
Wang, Ya-Xian
Hajkova, Alena
Nova, Alice
Frankova, Daniela
Prezeau, Laurent
Blahos, Jaroslav
TI Metabotropic glutamate receptor 1 splice variants mGluR1a and -mGluRlb
combine in mGluRla/b dimers in vivo
SO NEUROPHARMACOLOGY
LA English
DT Article
DE G-protein coupled receptors (GPCR); Metabotropic glutamate receptors;
Alternative splicing; Protein-protein interactions; Trafficking
ID ALLOSTERIC MODULATORS; HIPPOCAMPAL-NEURONS; ACTIVATION; REVEALS; DOMAIN
AB The assembly of two covalently linked monomers into dimeric complexes is a prerequisite for metabotropic glutamate receptor 1 (mGluR1) function. The former concept of a strictly homodimeric subunit contribution in metabotropic glutamate receptor complexes-has recently been brought into question. Alternative splicing of the GRM1 gene results in expression of variants that vary within their intracellular C-termini. Here we bring evidence that the short mGluRlb variant is found preferentially in a complex with the long mGluR1 a variant in the rodent brain. The mGluRla and mGluRlb variants distribution overlaps in Purkinje cells and the two variants colocalize in their spines. However mGluR1 a and mGluRlb show distinct sub-cellular localization when expressed alone in neurons. We discovered that trafficking of mGluRlb to distal dendrites is reliant on its association with mGluRla and that the long Cterminus of mGluR1 a within the mGluRla/b dimer is necessary for trafficking of the complex. (C) 2014 Elsevier Ltd. All rights reserved.
C1 [Techlovska, Sarka; Chambers, Jayne Nicole; Dvorakova, Michaela; Hajkova, Alena; Nova, Alice; Frankova, Daniela; Blahos, Jaroslav] Acad Sci Czech Republic, Inst Mol Genet, CR-14220 Prague 4, Czech Republic.
[Petralia, Ronald S.; Wang, Ya-Xian] NIDCD, NIH, Bethesda, MD 20892 USA.
[Prezeau, Laurent] CNRS, Inst Genom Fonct, UMR5203, Montpellier, France.
[Prezeau, Laurent] INSERM, U661, Montpellier, France.
[Prezeau, Laurent] Univ Montpellier I, F-34000 Montpellier, France.
[Prezeau, Laurent] Univ Montpellier 2, F-34000 Montpellier, France.
RP Blahos, J (reprint author), Acad Sci Czech Republic, Inst Mol Genet, Videnska 1083, CR-14220 Prague 4, Czech Republic.
EM blahos@img.cas.cz
FU Czech Science Foundation [GACR P303/12/2408, RVO:68378050]; NIDCD/NIH
FX We would like to thank Jean-Philippe Pin from Montpellier for constant
support and inspiring critical discussions and Ondrej Horvath for the
help with fluorescent microscopy. These studies were supported by the
Czech Science Foundation (GACR P303/12/2408) and RVO:68378050 to JB. RSP
and YXW were supported by the intramural research program of NIDCD/NIH.
NR 29
TC 3
Z9 3
U1 0
U2 3
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 NOV
PY 2014
VL 86
BP 329
EP 336
DI 10.1016/j.neuropharm.2014.08.011
PG 8
WC Neurosciences; Pharmacology & Pharmacy
SC Neurosciences & Neurology; Pharmacology & Pharmacy
GA AR8QN
UT WOS:000343839800034
PM 25158311
ER
PT J
AU Lee, R
Apkarian, K
Jung, ES
Yanjanin, N
Yoshida, S
Mori, S
Park, J
Gropman, A
Baker, EH
Porter, FD
AF Lee, Ryan
Apkarian, Kalyna
Jung, Eun Sol
Yanjanin, Nicole
Yoshida, Shoko
Mori, Susumu
Park, Jina
Gropman, Andrea
Baker, Eva H.
Porter, Forbes D.
TI Corpus Callosum Diffusion Tensor Imaging and Volume Measures Are
Associated With Disease Severity in Pediatric Niemann-Pick Disease Type
C1
SO PEDIATRIC NEUROLOGY
LA English
DT Article
DE NPC; DTI; corpus callosum; volume; severity; Niemann-Pick; diffusion
tensor
ID CYCLODEXTRIN; MIGLUSTAT; PATHOLOGY; ONSET; WHITE
AB BACKGROUND: Niemann-Pick disease type C1 is a neurodegenerative lysosomal storage disorder. Without a highly effective treatment, biomarkers of severity would be beneficial for prognostication and testing new interventions. Diffusion tensor imaging has shown microstructural abnormalities in adults with Niemann-Pick disease type C1. This is the first study to apply diffusion tensor imaging and volume analysis to evaluate the corpus callosum in a pediatric and adolescent population of patients with Niemann-Pick disease type C1. We hypothesized that the callosal fractional anisotropy, volume, and cross-sectional area will negatively correlate with NPC severity score. METHODS: Thirty-nine individuals with Niemann-Pick disease type C1 aged 1-21.9 years (mean = 111; S.D. = 6.1), and each received one magnetic resonance imaging examination. Severity score were obtained by examination and clinical observation. An atlas-based automated approach was used to measure fractional anisotropy, cross-sectional area, and volume. For comparative analysis and validation of this atlas-based approach, one midsagittal image was chosen and the corpus callosum manually traced to obtain cross-sectional area. Statistical analyses were applied to study the relationships between imaging and clinical severity. RESULTS: For patients with Niemann-Pick disease type C1, lower corpus callosum fractional anisotropy, volume, and cross-sectional area significantly correlate with higher severity score. Severity subdomain analysis revealed ambulation, speech, seizures, and incontinence have the strongest relationships with callosal measures. Comparison of atlas-based processing and manual tracing techniques demonstrated validity for the automated method. CONCLUSIONS: For individuals with Niemann-Pick disease type C1, the corpus callosum measures correlate with clinical severity. These findings reveal promise for the discovery of new imaging biomarkers for this disorder.
C1 [Lee, Ryan] Shriners Hosp Children Honolulu, Dept Neurol, Honolulu, HI 96826 USA.
[Lee, Ryan] Univ Hawaii, Dept Pediat, John A Burns Sch Med, Honolulu, HI 96822 USA.
[Apkarian, Kalyna] Johns Hopkins Univ, Dept Biomed Engn, Whiting Sch Engn, Baltimore, MD USA.
[Jung, Eun Sol] Kennedy Krieger Inst, Dept Psychiat, Baltimore, MD USA.
[Yanjanin, Nicole; Porter, Forbes D.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
[Yoshida, Shoko; Mori, Susumu] Johns Hopkins Univ, Sch Med, Dept Radiol, Baltimore, MD 21205 USA.
[Park, Jina] NYU, Sch Med, New York, NY 21205 USA.
[Gropman, Andrea] Childrens Natl Med Ctr, Div Neurogenet, Washington, DC 20010 USA.
[Baker, Eva H.] NIH, Dept Radiol & Imaging Sci, Bethesda, MD 20892 USA.
RP Lee, R (reprint author), Shriners Hosp Children Honolulu, 1310 Punahou St, Honolulu, HI 96826 USA.
EM rylee@shrinenet.org
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development, National Institutes of Health (NIH); NIH Clinical Center;
Ara Parseghian Medical Research Foundation; Office of Rare Diseases
FX The authors report no conflicts of interest. This work was supported by
the intramural research program of the Eunice Kennedy Shriver National
Institute of Child Health and Human Development, National Institutes of
Health (NIH). The authors thank the magnetic resonance imaging
technologists who acquired the images for this project (Mastaneh Owhadi
RT, Bonita Damaska RT, and Betty Wise RT). The authors express their
appreciation to the families and patients who participated in these
studies. This article was supported by a Bench to Bedside award from the
NIH Clinical Center and Office of Rare Diseases. This article was
supported by the Ara Parseghian Medical Research Foundation.
NR 32
TC 3
Z9 3
U1 0
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0887-8994
EI 1873-5150
J9 PEDIATR NEUROL
JI Pediatr. Neurol.
PD NOV
PY 2014
VL 51
IS 5
BP 669
EP 674
DI 10.1016/j.pediatrneurol.2014.07.028
PG 6
WC Clinical Neurology; Pediatrics
SC Neurosciences & Neurology; Pediatrics
GA AS0GF
UT WOS:000343955400014
PM 25194719
ER
PT J
AU Boland, S
Hussain, S
Baeza-Squiban, A
AF Boland, Sonja
Hussain, Salik
Baeza-Squiban, Armelle
TI Carbon black and titanium dioxide nanoparticles induce distinct
molecular mechanisms of toxicity
SO WILEY INTERDISCIPLINARY REVIEWS-NANOMEDICINE AND NANOBIOTECHNOLOGY
LA English
DT Review
ID LUNG EPITHELIAL-CELLS; TIO2 NANOPARTICLES; OXIDATIVE STRESS;
SURFACE-AREA; NANOMATERIALS; APOPTOSIS; INFLAMMATION; PARTICLES;
ULTRAFINE; EXPOSURE
AB Increasing evidence link nanomaterials with adverse biological outcomes and due to the variety of applications and potential human exposures to nanoparticles, it is thus important to evaluate their toxicity for the risk assessment of workers and consumers. It is crucial to understand the underlying mechanisms of their toxicity as observation of similar effects after different nanomaterial exposures does not reflect similar intracellular processing and organelle interactions. A thorough understanding of mechanisms is needed not only for accurate prediction of potential toxicological impacts but also for the development of safer nanoapplications by modulating the physicochemical characteristics. Furthermore biomedical applications may also take advantage of an in depth knowledge about the mode of action of nanotoxicity to design new nanoparticle-derived drugs. In the present manuscript we discuss the similarities and differences in molecular pathways of toxicity after carbon black (CB) and titanium dioxide (TiO2) nanoparticle exposures and identify the main toxicity mechanisms induced by these two nanoparticles which may also be indicative for the mode of action of other insoluble nanomaterials. We address the translocation, cell death induction, genotoxicity, and inflammation induced by TiO2 and CB nanoparticles which depend on their internalization, reactive oxygen species (ROS) production capacities and/or protein interactions. We summarize their distinct cellular mechanisms of toxicity and the crucial steps which may be targeted to avoid adverse effects or to induce them for nanomedical purposes. Several physicochemical characteristics could influence these general toxicity pathways depicted here and the identification of common toxicity pathways could support the grouping of nanomaterials in terms of toxicity. WIREs Nanomed Nanobiotechnol 2014, 6:641-652. doi: 10.1002/wnan.1302 For further resources related to this article, please visit the . Conflict of interest: The authors have declared no conflicts of interest for this article.
C1 [Boland, Sonja; Baeza-Squiban, Armelle] Univ Paris Diderot, Sorbonne Paris Cite, Lab Mol & Cellular Responses Xenobiot RMCX, Unit Funct & Adapt Biol BFA,CNRS,UMR 8251, Paris, France.
[Hussain, Salik] NIEHS, Clin Res Program, Res Triangle Pk, NC 27709 USA.
RP Boland, S (reprint author), Univ Paris Diderot, Sorbonne Paris Cite, Lab Mol & Cellular Responses Xenobiot RMCX, Unit Funct & Adapt Biol BFA,CNRS,UMR 8251, Paris, France.
EM boland@univ-paris-diderot.fr
RI Hussain, Salik/O-1687-2016
FU Intramural Research Program of the NIH, National Institute of
Environmental Health Sciences (NIEHS); French National Research Agency
(ANR); German Federal Ministry of Education and Research (BMBF)
FX This work was supported (in part) by the Intramural Research Program of
the NIH, National Institute of Environmental Health Sciences (NIEHS) and
by the French National Research Agency (ANR) and the German Federal
Ministry of Education and Research (BMBF), under the frame of SIINN, the
ERA-NET for a Safe Implementation of Innovative Nanoscience and
Nanotechnology.
NR 55
TC 4
Z9 5
U1 7
U2 79
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1939-5116
EI 1939-0041
J9 WIRES NANOMED NANOBI
JI Wiley Interdiscip. Rev.-Nanomed. Nanobiotechnol.
PD NOV-DEC
PY 2014
VL 6
IS 6
BP 641
EP 652
DI 10.1002/wnan.1302
PG 12
WC Nanoscience & Nanotechnology; Medicine, Research & Experimental
SC Science & Technology - Other Topics; Research & Experimental Medicine
GA AR8KF
UT WOS:000343823300009
PM 25266826
ER
PT J
AU Manrique, A
Adams, E
Barouch, DH
Fast, P
Graham, BS
Kim, JH
Kublin, JG
McCluskey, M
Pantaleo, G
Robinson, HL
Russell, N
Snow, W
Johnston, MI
AF Manrique, Amapola
Adams, Elizabeth
Barouch, Dan H.
Fast, Pat
Graham, Barney S.
Kim, Jerome H.
Kublin, James G.
McCluskey, Margaret
Pantaleo, Giuseppe
Robinson, Harriet L.
Russell, Nina
Snow, William
Johnston, Margaret I.
TI The Immune Space: A Concept and Template for Rationalizing Vaccine
Development
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Editorial Material
ID IMMUNODEFICIENCY-VIRUS TYPE-1; B-CELL RECEPTORS; HIV-1; OPTIMIZATION;
DESIGN; TRIAL; ASSAY
AB Empirical testing of candidate vaccines has led to the successful development of a number of lifesaving vaccines. The advent of new tools to manipulate antigens and new methods and vectors for vaccine delivery has led to a veritable explosion of potential vaccine designs. As a result, selection of candidate vaccines suitable for large-scale efficacy testing has become more challenging. This is especially true for diseases such as dengue, HIV, and tuberculosis where there is no validated animal model or correlate of immune protection. Establishing guidelines for the selection of vaccine candidates for advanced testing has become a necessity. A number of factors could be considered in making these decisions, including, for example, safety in animal and human studies, immune profile, protection in animal studies, production processes with product quality and stability, availability of resources, and estimated cost of goods. The "immune space template" proposed here provides a standardized approach by which the quality, level, and durability of immune responses elicited in early human trials by a candidate vaccine can be described. The immune response profile will demonstrate if and how the candidate is unique relative to other candidates, especially those that have preceded it into efficacy testing and, thus, what new information concerning potential immune correlates could be learned from an efficacy trial. A thorough characterization of immune responses should also provide insight into a developer's rationale for the vaccine's proposed mechanism of action. HIV vaccine researchers plan to include this general approach in up-selecting candidates for the next large efficacy trial. This "immune space" approach may also be applicable to other vaccine development endeavors where correlates of vaccine-induced immune protection remain unknown.
C1 [Manrique, Amapola; Snow, William] Global HIV Vaccine Enterprise, New York, NY 10004 USA.
[Adams, Elizabeth] NIAID, Div Aids, Bethesda, MD 20892 USA.
[Barouch, Dan H.] Beth Israel Deaconess Med Ctr, Ctr Virol & Vaccine Res, Boston, MA 02215 USA.
[Fast, Pat] Int AIDS Vaccine Initiat, New York, NY USA.
[Graham, Barney S.] NIAID, Vaccine Res Ctr, Bethesda, MD 20892 USA.
[Kim, Jerome H.] Walter Reed Army Inst Res, US Mil HIV Res Program, Silver Spring, MD USA.
[Kublin, James G.] Fred Hutchinson Canc Res Ctr, HIV Vaccine Trials Network, Seattle, WA 98104 USA.
[Kublin, James G.] Fred Hutchinson Canc Res Ctr, Vaccine & Infect Dis Inst, Seattle, WA 98104 USA.
[McCluskey, Margaret] USAID, Washington, DC USA.
[Pantaleo, Giuseppe] Univ Lausanne, Div Immunol & Allergy, Univ Lausanne Hosp, Lausanne, Switzerland.
[Robinson, Harriet L.] GeoVax Inc, Smyrna, GA USA.
[Russell, Nina; Johnston, Margaret I.] Bill & Melinda Gates Fdn, Seattle, WA USA.
RP Manrique, A (reprint author), Global HIV Vaccine Enterprise, 64 Beaver St,352, New York, NY 10004 USA.
EM amanrique@vaccineenterprise.org
RI Pantaleo, Giuseppe/K-6163-2016
NR 19
TC 7
Z9 7
U1 2
U2 7
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 0889-2229
EI 1931-8405
J9 AIDS RES HUM RETROV
JI Aids Res. Hum. Retrovir.
PD NOV 1
PY 2014
VL 30
IS 11
BP 1017
EP 1022
DI 10.1089/aid.2014.0040
PG 6
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA AR7OY
UT WOS:000343770300001
PM 24857015
ER
PT J
AU Forsell, MNE
McKee, K
Feng, Y
Mascola, JR
Wyatt, RT
AF Forsell, Mattias N. E.
McKee, Krisha
Feng, Yu
Mascola, John R.
Wyatt, Richard T.
TI HIV-1 Envelope Glycoprotein Trimer Immunogenicity Elicited in the
Presence of Human CD4 Alters the Neutralization Profile
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Article
ID IMMUNODEFICIENCY-VIRUS TYPE-1; PLASMACYTOID DENDRITIC CELLS; CORECEPTOR
BINDING-SITE; MOLECULAR ARCHITECTURE; MONOCLONAL-ANTIBODIES; CD4-BINDING
SITE; GP120; BROAD; VACCINATION; CHALLENGE
AB The HIV-1 envelope glycoproteins (Env) gp120 and gp41 are the sole virally derived components on the surface of the virus. These glycoproteins mediate receptor binding and entry and are targets for neutralizing antibodies. The most highly validated protein region on Env that is a target for broadly neutralizing antibodies is the conserved CD4 binding site. Mimetics of Env have been used in attempts to elicit antibodies to the CD4 binding site. Some trimers, such as the soluble foldon trimers used here, elicit 5-10% of the Env-directed B cell response to this conserved region. As these trimers, or other Env versions, advance into clinical development, there is both considerable interest and concern as to whether binding to the abundant CD4 present on the surface of T cells and macrophages may blunt potentially protective antibody responses to this site. Here, we utilized rabbits transgenic for human CD4 to evaluate the role of CD4:Env interaction in vivo relative to the elicitation of Env-directed antibodies following immunization. We analyzed responses to trimers both capable and incapable of recognizing human CD4 with high affinity. We demonstrated that the presence of human CD4 in vivo did not significantly affect the overall elicitation of Env binding or CD4bs-directed antibodies. However, the presence of CD4 did reduce the capacity of elicited serum antibodies to neutralize the clade C isolate, MW965. Reduction of HXBc2 neutralization was associated with the CD4 binding-incompetent trimers. These results highlight an important consideration regarding CD4 binding-competent trimeric Env immunogens as they enter the clinic for human vaccine trials.
C1 [Forsell, Mattias N. E.; McKee, Krisha; Feng, Yu; Mascola, John R.; Wyatt, Richard T.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Forsell, Mattias N. E.] Karolinska Inst, Dept Microbiol Tumor & Cell Biol, Stockholm, Sweden.
RP Wyatt, RT (reprint author), Scripps Res Inst, IAVI Neutralizing Antibody Ctr TSRI, 10550 North Torry Pines Rd, La Jolla, CA 92037 USA.
EM wyatt@scripps.edu
FU International AIDS Vaccine Initiative; NIH
FX We thank Gunilla Karlsson Hedestam for helpful discussions and Javier
Guenaga for excellent technical assistance. The Env-directed mAb b12 was
kindly provided by Dennis Burton (The Scripps Research Institute). This
study was supported by the International AIDS Vaccine Initiative and NIH
to R.T.W. and J.R.M. M.N.E.F. is a Mathilde Krim fellow in basic
biomedical research (108213-51-RKVA).
NR 34
TC 3
Z9 3
U1 0
U2 0
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 0889-2229
EI 1931-8405
J9 AIDS RES HUM RETROV
JI Aids Res. Hum. Retrovir.
PD NOV 1
PY 2014
VL 30
IS 11
BP 1089
EP 1098
DI 10.1089/aid.2014.0104
PG 10
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA AR7OY
UT WOS:000343770300011
PM 25245278
ER
PT J
AU Tasevska, N
Park, Y
Subar, AF
Potischman, N
AF Tasevska, Natasha
Park, Yikyung
Subar, Amy F.
Potischman, Nancy
TI Differential association of sugar-sweetened beverages in men and women:
is it the sugar or calories? Reply
SO AMERICAN JOURNAL OF CLINICAL NUTRITION
LA English
DT Letter
ID ENERGY NUTRITION OPEN; OBSERVING PROTEIN; BIOMARKER; MORTALITY; COHORT
C1 [Tasevska, Natasha] Arizona State Univ, Sch Nutr & Hlth Promot, Nutr Program, Phoenix, AZ 85004 USA.
[Park, Yikyung] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Subar, Amy F.; Potischman, Nancy] NCI, Appl Res Program, Div Canc Control & Populat Sci, NIH, Bethesda, MD 20892 USA.
RP Tasevska, N (reprint author), Arizona State Univ, Sch Nutr & Hlth Promot, Nutr Program, 500 North Third St, Phoenix, AZ 85004 USA.
EM natasha.tasevska@asu.edu
FU Intramural NIH HHS
NR 6
TC 0
Z9 0
U1 1
U2 4
PU AMER SOC NUTRITION-ASN
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0002-9165
EI 1938-3207
J9 AM J CLIN NUTR
JI Am. J. Clin. Nutr.
PD NOV
PY 2014
VL 100
IS 5
BP 1400
EP 1401
DI 10.3945/ajcn.114.094433
PG 2
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA AR3ZT
UT WOS:000343528500025
PM 25332342
ER
PT J
AU Kant, AK
Graubard, BI
AF Kant, Ashima K.
Graubard, Barry I.
TI Sleep duration and energy intake: timing matters Reply
SO AMERICAN JOURNAL OF CLINICAL NUTRITION
LA English
DT Letter
C1 [Kant, Ashima K.] CUNY Queens Coll, Dept Family Nutr & Exercise Sci, Flushing, NY 11367 USA.
[Graubard, Barry I.] NCI, Biostat Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
RP Kant, AK (reprint author), CUNY Queens Coll, Dept Family Nutr & Exercise Sci, Remsen Hall,Room 306E, Flushing, NY 11367 USA.
EM ashima.kant@qc.cuny.edu
NR 3
TC 0
Z9 0
U1 0
U2 2
PU AMER SOC NUTRITION-ASN
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0002-9165
EI 1938-3207
J9 AM J CLIN NUTR
JI Am. J. Clin. Nutr.
PD NOV
PY 2014
VL 100
IS 5
BP 1403
EP 1404
DI 10.3945/ajcn.114.096966
PG 2
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA AR3ZT
UT WOS:000343528500028
PM 25332345
ER
PT J
AU Gounden, V
Celi, FS
Soldin, SJ
AF Gounden, Verena
Celi, Francesco S.
Soldin, Steven J.
TI Case Studies Illustrating the Clinical Utility of Liquid
Chromatography-Tandem Mass Spectrometry for the Assessment of Free
Thyroid Hormone Status
SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY
LA English
DT Meeting Abstract
CT 49th Annual Meeting of
Academy-of-Clinical-Laboratory-Physicians-and-Scientists (ACLPS) /
Conference on Lab Medicine
CY MAY 29-31, 2014
CL San Francisco, CA
SP Acad Clin Lab Phys & Scientists
C1 [Gounden, Verena; Soldin, Steven J.] NIH, Dept Lab Med, Bethesda, MD 20892 USA.
[Celi, Francesco S.] NIDDK, NIH, Bethesda, MD 20892 USA.
[Celi, Francesco S.] Virginia Commonwealth Univ, Div Endocrinol & Metab, Richmond, VA USA.
[Soldin, Steven J.] Georgetown Univ, Dept Med, Washington, DC USA.
NR 0
TC 0
Z9 0
U1 2
U2 2
PU AMER SOC CLINICAL PATHOLOGY
PI CHICAGO
PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA
SN 0002-9173
EI 1943-7722
J9 AM J CLIN PATHOL
JI Am. J. Clin. Pathol.
PD NOV
PY 2014
VL 142
IS 5
MA 8
BP 701
EP 702
PG 2
WC Pathology
SC Pathology
GA AR6IJ
UT WOS:000343687100025
ER
PT J
AU Fernandez, E
Watterberg, KL
Faix, RG
Yoder, BA
Walsh, MC
Lacy, CB
Osborne, KA
Das, A
Kendrick, DE
Stoll, BJ
Poindexter, BB
Laptook, AR
Kennedy, KA
Schibler, K
Bell, EF
Van Meurs, KP
Frantz, ID
Goldberg, RN
Shankaran, S
Carlo, WA
Ehrenkranz, RA
Sanchez, PJ
Higgins, RD
AF Fernandez, Erika
Watterberg, Kristi L.
Faix, Roger G.
Yoder, Bradley A.
Walsh, Michele C.
Lacy, Conra Backstrom
Osborne, Karen A.
Das, Abhik
Kendrick, Douglas E.
Stoll, Barbara J.
Poindexter, Brenda B.
Laptook, Abbot R.
Kennedy, Kathleen A.
Schibler, Kurt
Bell, Edward F.
Van Meurs, Krisa P.
Frantz, Ivan D., III
Goldberg, Ronald N.
Shankaran, Seetha
Carlo, Waldemar A.
Ehrenkranz, Richard A.
Sanchez, Pablo J.
Higgins, Rosemary D.
TI Incidence, Management, and Outcomes of Cardiovascular Insufficiency in
Critically III Term and Late Preterm Newborn Infants
SO AMERICAN JOURNAL OF PERINATOLOGY
LA English
DT Article
DE blood pressure; cardiovascular insufficiency; mechanical ventilation;
inotrope; fluid bolus; glucocorticoid; outcomes; newborn
ID BLOOD-PRESSURE-MEASUREMENTS; INTENSIVE-CARE-UNIT; HYPOTENSION;
GUIDELINES; UPDATE
AB Objective The objective of this study was to characterize the incidence, management, and short-term outcomes of cardiovascular insufficiency (CV!) in mechanically ventilated newborns, evaluating four separate prespecified definitions.
Study Design Multicenter, prospective cohort study of infants >= 34 weeks gestational age (GA) and on mechanical ventilation during the first 72 hours. CVI was prospectively defined as either (1) mean arterial pressure (MAP) < GA; (2) MAP < GA + signs of inadequate perfusion; (3) any therapy for CVI; or (4) inotropic therapy. Short-term outcomes included death, days on ventilation, oxygen, and to full feedings and discharge.
Results Of 647 who met inclusion criteria, 419 (65%) met >= 1 definition of CVI. Of these, 98% received fluid boluses, 36% inotropes, and 17% corticosteroids. Of treated infants, 46% did not have CVI as defined by a MAP < GA +/- signs of inadequate perfusion. Inotropic therapy was associated with increased mortality (11.1 vs. 1.3%; p < 0.05).
Conclusion More than half of the infants met at least one definition of CVI. However, almost half of the treated infants met none of the definitions. Inotropic therapy was associated with increased mortality. These findings can help guide the design of future studies of CVI in newborns.
C1 [Fernandez, Erika; Watterberg, Kristi L.; Lacy, Conra Backstrom] Univ New Mexico, Hlth Sci Ctr, Dept Pediat, Albuquerque, NM 87131 USA.
[Faix, Roger G.] Univ Utah, Sch Med, Dept Pediat, Div Neonatol, Salt Lake City, UT USA.
[Yoder, Bradley A.; Walsh, Michele C.; Osborne, Karen A.] Case Western Reserve Univ, Rainbow Babies & Childrens Hosp, Dept Pediat, Cleveland, OH 44106 USA.
[Das, Abhik] RTI Int, Stat & Epidemiol Unit, Rockville, MD USA.
[Kendrick, Douglas E.] RTI Int, Stat & Epidemiol Unit, Res Triangle Pk, NC USA.
[Stoll, Barbara J.] Emory Univ, Sch Med, Dept Pediat, Childrens Healthcare Atlanta, Atlanta, GA USA.
[Poindexter, Brenda B.] Indiana Univ Sch Med, Dept Pediat, Indianapolis, IN 46202 USA.
[Laptook, Abbot R.] Brown Univ, Women & Infants Hosp, Dept Pediat, Providence, RI 02908 USA.
[Kennedy, Kathleen A.] Univ Texas Med Sch Houston, Dept Pediat, Houston, TX USA.
[Schibler, Kurt] Univ Cincinnati, Coll Med, Dept Pediat, Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH USA.
[Bell, Edward F.] Univ Iowa, Dept Pediat, Iowa City, IA 52242 USA.
[Van Meurs, Krisa P.] Stanford Univ, Sch Med, Dept Pediat, Div Neonatal & Dev Med,Lucile Packard Childrens H, Palo Alto, CA 94304 USA.
[Frantz, Ivan D., III] Tufts Med Ctr, Floating Hosp Children, Dept Pediat, Div Newborn Med, Boston, MA USA.
[Goldberg, Ronald N.] Duke Univ, Dept Pediat, Durham, NC 27706 USA.
[Shankaran, Seetha] Wayne State Univ, Dept Pediat, Detroit, MI 48202 USA.
[Carlo, Waldemar A.] Univ Alabama Birmingham, Div Neonatol, Birmingham, AL USA.
[Ehrenkranz, Richard A.] Yale Univ, Sch Med, Dept Pediat, New Haven, CT 06510 USA.
[Sanchez, Pablo J.] Univ Texas SW Med Ctr Dallas, Dept Pediat, Dallas, TX 75390 USA.
[Higgins, Rosemary D.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
RP Fernandez, E (reprint author), 1 Univ New Mexico, Childrens Hosp New Mexico, Dept Pediat, MSC10 5590, Albuquerque, NM 87131 USA.
EM efernandez@salud.unm.edu
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development Neonatal Research Network
FX This study was funded by the Eunice Kennedy Shriver National Institute
of Child Health and Human Development Neonatal Research Network.
NR 17
TC 1
Z9 1
U1 0
U2 3
PU THIEME MEDICAL PUBL INC
PI NEW YORK
PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA
SN 0735-1631
EI 1098-8785
J9 AM J PERINAT
JI Am. J. Perinatol.
PD NOV
PY 2014
VL 31
IS 11
BP 947
EP 955
DI 10.1055/s-0034-1368089
PG 9
WC Obstetrics & Gynecology; Pediatrics
SC Obstetrics & Gynecology; Pediatrics
GA AR1KT
UT WOS:000343344800004
PM 24515617
ER
PT J
AU Romero, R
Miranda, J
Chaiworapongsa, T
Korzeniewski, SJ
Chaemsaithong, P
Gotsch, F
Dong, Z
Ahmed, AI
Yoon, BH
Hassan, SS
Kim, CJ
Yeo, L
AF Romero, Roberto
Miranda, Jezid
Chaiworapongsa, Tinnakorn
Korzeniewski, Steven J.
Chaemsaithong, Piya
Gotsch, Francesca
Dong, Zhong
Ahmed, Ahmed I.
Yoon, Bo Hyun
Hassan, Sonia S.
Kim, Chong Jai
Yeo, Lami
TI Prevalence and Clinical Significance of Sterile Intra-amniotic
Inflammation in Patients with Preterm Labor and Intact Membranes
SO AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY
LA English
DT Article
DE Alarmins; danger signal; high mobility group box-1; polymerase chain
reaction with electrospray ionization mass spectrometry; pregnancy;
preterm delivery
ID TUMOR-NECROSIS-FACTOR; AMNIOTIC-FLUID INFECTION; MOBILITY GROUP BOX-1;
TOLL-LIKE RECEPTORS; HUMAN FETAL MEMBRANES; ACTIVATING PEPTIDE-1
INTERLEUKIN-8; MONOCYTE CHEMOTACTIC PROTEIN-1; IONIZATION
MASS-SPECTROMETRY; INNATE IMMUNE RECOGNITION; GLYCATION END-PRODUCTS
AB ProblemInflammation and infection play a major role in preterm birth. The purpose of this study was to (i) determine the prevalence and clinical significance of sterile intra-amniotic inflammation and (ii) examine the relationship between amniotic fluid (AF) concentrations of high mobility group box-1 (HMGB1) and the interval from amniocentesis to delivery in patients with sterile intra-amniotic inflammation.
Method of studyAF samples obtained from 135 women with preterm labor and intact membranes were analyzed using cultivation techniques as well as broad-range PCR and mass spectrometry (PCR/ESI-MS). Sterile intra-amniotic inflammation was defined when patients with negative AF cultures and without evidence of microbial footprints had intra-amniotic inflammation (AF interleukin-62.6ng/mL).
Results(i) The frequency of sterile intra-amniotic inflammation was significantly greater than that of microbial-associated intra-amniotic inflammation [26% (35/135) versus 11% (15/135); (P=0.005)], (ii) patients with sterile intra-amniotic inflammation delivered at comparable gestational ages had similar rates of acute placental inflammation and adverse neonatal outcomes as patients with microbial-associated intra-amniotic inflammation, and (iii) patients with sterile intra-amniotic inflammation and high AF concentrations of HMGB1 (8.55ng/mL) delivered earlier than those with low AF concentrations of HMGB1 (P=0.02).
Conclusion(i) Sterile intra-amniotic inflammation is more frequent than microbial-associated intra-amniotic inflammation, and (ii) we propose that danger signals participate in sterile intra-amniotic inflammation in the setting of preterm labor.
C1 [Romero, Roberto; Miranda, Jezid; Chaiworapongsa, Tinnakorn; Korzeniewski, Steven J.; Chaemsaithong, Piya; Gotsch, Francesca; Dong, Zhong; Ahmed, Ahmed I.; Hassan, Sonia S.; Kim, Chong Jai; Yeo, Lami] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, Program Perinatal Res & Obstet, Div Intramural Res,NIH, Bethesda, MD USA.
[Romero, Roberto; Miranda, Jezid; Chaiworapongsa, Tinnakorn; Korzeniewski, Steven J.; Chaemsaithong, Piya; Gotsch, Francesca; Dong, Zhong; Ahmed, Ahmed I.; Hassan, Sonia S.; Kim, Chong Jai; Yeo, Lami] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, Program Perinatal Res & Obstet, Div Intramural Res,NIH, Detroit, MI USA.
[Romero, Roberto] Univ Michigan, Dept Obstet & Gynecol, Ann Arbor, MI 48109 USA.
[Romero, Roberto] Michigan State Univ, Dept Epidemiol & Biostat, E Lansing, MI 48824 USA.
[Miranda, Jezid; Chaiworapongsa, Tinnakorn; Korzeniewski, Steven J.; Chaemsaithong, Piya; Dong, Zhong; Ahmed, Ahmed I.; Hassan, Sonia S.; Yeo, Lami] Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA.
[Gotsch, Francesca] Azienda Osped Univ, Verona, Italy.
[Yoon, Bo Hyun] Seoul Natl Univ, Coll Med, Dept Obstet & Gynecol, Seoul, South Korea.
[Kim, Chong Jai] Univ Ulsan, Coll Med, Asan Med Ctr, Dept Pathol, Seoul, South Korea.
RP Romero, R (reprint author), Wayne State Univ, Hutzel Womens Hosp, Perinatol Res Branch, NICHD NIH DHHS, 3990 John R,Box 4, Detroit, MI 48201 USA.
EM romeror@mail.nih.gov
FU Perinatology Research Branch, Division of Intramural Research, Eunice
Kennedy Shriver National Institute of Child Health and Human
Development, National Institutes of Health, Department of Health and
Human Services (NICHD/NIH); NICHD, NIH [HHSN275201300006C]
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, National Institutes of
Health, Department of Health and Human Services (NICHD/NIH) and, in
part, with Federal funds from NICHD, NIH under Contract No.
HHSN275201300006C.
NR 237
TC 53
Z9 56
U1 0
U2 5
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1046-7408
EI 1600-0897
J9 AM J REPROD IMMUNOL
JI Am. J. Reprod. Immunol.
PD NOV
PY 2014
VL 72
IS 5
BP 458
EP 474
DI 10.1111/aji.12296
PG 17
WC Immunology; Reproductive Biology
SC Immunology; Reproductive Biology
GA AR7AG
UT WOS:000343731800003
PM 25078709
ER
PT J
AU Lv, QW
Zhang, W
Shi, Q
Zheng, WJ
Lipsky, PE
Zhang, X
AF Lv, Qian-wen
Zhang, Wen
Shi, Qun
Zheng, Wen-jie
Lipsky, Peter E.
Zhang, Xuan
TI The TRIFRA trial: efforts employed to minimise expectation bias
SO ANNALS OF THE RHEUMATIC DISEASES
LA English
DT Letter
ID WILFORDII HOOK-F; RHEUMATOID-ARTHRITIS
C1 [Lv, Qian-wen; Zhang, Wen; Shi, Qun; Zheng, Wen-jie; Zhang, Xuan] Chinese Acad Med Sci, Dept Rheumatol & Clin Immunol, Peking Union Med Coll Hosp, Beijing 100730, Peoples R China.
[Lv, Qian-wen; Zhang, Wen; Shi, Qun; Zheng, Wen-jie; Zhang, Xuan] Peking Union Med Coll, Beijing 100730, Peoples R China.
[Lipsky, Peter E.] NIAMSD, NIH, Bethesda, MD 20892 USA.
RP Zhang, X (reprint author), Chinese Acad Med Sci, Dept Rheumatol & Clin Immunol, Peking Union Med Coll Hosp, Beijing 100730, Peoples R China.
EM peterlipsky@comcast.net; zxpumch2003@sina.com
OI zhang, xuan/0000-0001-8775-1699
NR 4
TC 0
Z9 0
U1 0
U2 1
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0003-4967
EI 1468-2060
J9 ANN RHEUM DIS
JI Ann. Rheum. Dis.
PD NOV
PY 2014
VL 73
IS 11
BP E67
EP E67
DI 10.1136/annrheumdis-2014-206197
PG 1
WC Rheumatology
SC Rheumatology
GA AR0ZR
UT WOS:000343308200002
PM 25057182
ER
PT J
AU Graham, AL
Gluck, ME
Votruba, SB
Krakoff, J
Thearle, MS
AF Graham, Alexis L.
Gluck, Marci E.
Votruba, Susanne B.
Krakoff, Jonathan
Thearle, Marie S.
TI Perseveration augments the effects of cognitive restraint on ad libitum
food intake in adults seeking weight loss
SO APPETITE
LA English
DT Article
DE Energy intake; Obesity; Neuropsychological tests; Executive function;
Appetite regulation
ID 3-FACTOR EATING QUESTIONNAIRE; IOWA GAMBLING TASK; CARD SORTING TEST;
DIETARY RESTRAINT; OBESE INDIVIDUALS; BEHAVIOR; SELECTION;
DISINHIBITION; INTERVENTION; MAINTENANCE
AB As executive function may influence eating behaviors, our aim was to determine whether measures of executive function predict ad libitum food intake in subjects seeking weight loss. 78 obese, healthy individuals (40 female/38 male; age 36 +/- 10 y; BMI 37.8 +/- 7.2 kg/m(2)) completed the Iowa Gambling Task to evaluate decision making, the Stroop Word Color Task to assess attention, the Wisconsin Card Sorting Task to measure perseveration, and the Three Factor Eating Questionnaire to measure disinhibition and cognitive restraint. Ad libitum energy intake over 3-days was then collected using a validated vending paradigm. When expressed as a percentage of an individual's weight maintaining energy needs (%WMEN), intake correlated positively with perseveration (r = 0.24, p = 0.03) and negatively with restraint (r = -0.51, p < 0.0001). In a regression model of %WMEN (r(2) = 0.59, p < 0.0001), an interaction between perseveration and restraint was observed (p = 0.05). Increased perseveration intensified the effect of restraint such that subjects with both high restraint and perseveration ate the least (median (IQR) = 70 (62, 94) %WMEN), while those with low restraint and high perseveration ate the most (130 (102, 153) %WMEN). Subjects with low perseveration and high versus low restraint ate a median of 84 (70, 86) and 112(98, 133) %WMEN, respectively. The effects of perseveration on food intake are conditional on restraint, and may contribute to extremes of dietary intake in some individuals. Published by Elsevier Ltd.
C1 [Graham, Alexis L.; Gluck, Marci E.; Votruba, Susanne B.; Krakoff, Jonathan; Thearle, Marie S.] NIDDK, Phoenix Epidemiol & Clin Res Branch, NIH, Phoenix, AZ 85014 USA.
RP Thearle, MS (reprint author), NIDDK, Phoenix Epidemiol & Clin Res Branch, NIH, Phoenix, AZ 85014 USA.
EM thearlem@mail.nih.gov
FU National Institutes of Health (NIH); National Institute of Diabetes and
Digestive and Kidney Diseases (NIDDK)
FX Funding: This research was funded by the Intramural Research Program of
the National Institutes of Health (NIH) and the National Institute of
Diabetes and Digestive and Kidney Diseases (NIDDK). The funders had no
role in study design, data collection and analysis, decision to publish,
or preparation of the manuscript.
NR 39
TC 1
Z9 1
U1 1
U2 7
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0195-6663
EI 1095-8304
J9 APPETITE
JI Appetite
PD NOV 1
PY 2014
VL 82
BP 78
EP 84
DI 10.1016/j.appet.2014.07.008
PG 7
WC Behavioral Sciences; Nutrition & Dietetics
SC Behavioral Sciences; Nutrition & Dietetics
GA AR2AK
UT WOS:000343385500011
PM 25049138
ER
PT J
AU Strang, JF
Kenworthy, L
Dominska, A
Sokoloff, J
Kenealy, LE
Berl, M
Walsh, K
Menvielle, E
Slesaransky-Poe, G
Kim, KE
Luong-Tran, C
Meagher, H
Wallace, GL
AF Strang, John F.
Kenworthy, Lauren
Dominska, Aleksandra
Sokoloff, Jennifer
Kenealy, Laura E.
Berl, Madison
Walsh, Karin
Menvielle, Edgardo
Slesaransky-Poe, Graciela
Kim, Kyung-Eun
Luong-Tran, Caroline
Meagher, Haley
Wallace, Gregory L.
TI Increased Gender Variance in Autism Spectrum Disorders and Attention
Deficit Hyperactivity Disorder
SO ARCHIVES OF SEXUAL BEHAVIOR
LA English
DT Article
DE Gender variance; Gender identity; Autism; Attention deficit
hyperactivity disorder; Gender dysphoria
ID PERVASIVE DEVELOPMENTAL DISORDERS; IDENTITY-DISORDER; BEHAVIOR PROBLEMS;
PSYCHIATRIC COMORBIDITY; DIAGNOSTIC INTERVIEW; ADAPTIVE-BEHAVIOR;
ASPERGER-SYNDROME; CHILDREN; ADOLESCENTS; MANAGEMENT
AB Evidence suggests over-representation of autism spectrum disorders (ASDs) and behavioral difficulties among people referred for gender issues, but rates of the wish to be the other gender (gender variance) among different neurodevelopmental disorders are unknown. This chart review study explored rates of gender variance as reported by parents on the Child Behavior Checklist (CBCL) in children with different neurodevelopmental disorders: ASD (N=147, 24 females and 123 males), attention deficit hyperactivity disorder (ADHD; N=126, 38 females and 88 males), or a medical neurodevelopmental disorder (N=116, 57 females and 59 males), were compared with two non-referred groups [control sample (N=165, 61 females and 104 males) and non-referred participants in the CBCL standardization sample (N=1,605, 754 females and 851 males)]. Significantly greater proportions of participants with ASD (5.4%) or ADHD (4.8%) had parent reported gender variance than in the combined medical group (1.7%) or non-referred comparison groups (0-0.7 %). As compared to non-referred comparisons, participants with ASD were 7.59 times more likely to express gender variance; participants with ADHD were 6.64 times more likely to express gender variance. The medical neurodevelopmental disorder group did not differ from non-referred samples in likelihood to express gender variance. Gender variance was related to elevated emotional symptoms in ADHD, but not in ASD. After accounting for sex ratio differences between the neurodevelopmental disorder and non-referred comparison groups, gender variance occurred equally in females and males.
C1 [Strang, John F.; Kenworthy, Lauren; Sokoloff, Jennifer; Luong-Tran, Caroline; Meagher, Haley] Childrens Natl Med Ctr, Ctr Autism Spectrum Disorders, Rockville, MD 20850 USA.
[Dominska, Aleksandra; Kenealy, Laura E.; Berl, Madison; Walsh, Karin] Childrens Natl Med Ctr, Div Neuropsychol, Rockville, MD 20850 USA.
[Menvielle, Edgardo; Kim, Kyung-Eun] Childrens Natl Med Ctr, Dept Psychiat, Washington, DC 20010 USA.
[Slesaransky-Poe, Graciela] Arcadia Univ, Sch Educ, Glenside, PA USA.
[Wallace, Gregory L.] NIMH, Lab Brain & Cognit, Bethesda, MD 20892 USA.
RP Strang, JF (reprint author), Childrens Natl Med Ctr, Ctr Autism Spectrum Disorders, 15245 Shady Grove Rd,Suite 350, Rockville, MD 20850 USA.
EM jstrang@cnmc.org
OI Walsh, Karin/0000-0001-9637-2164; Wallace, Gregory/0000-0003-0329-5054
NR 52
TC 9
Z9 9
U1 5
U2 31
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0004-0002
EI 1573-2800
J9 ARCH SEX BEHAV
JI Arch. Sex. Behav.
PD NOV
PY 2014
VL 43
IS 8
BP 1525
EP 1533
DI 10.1007/s10508-014-0285-3
PG 9
WC Psychology, Clinical; Social Sciences, Interdisciplinary
SC Psychology; Social Sciences - Other Topics
GA AR9PW
UT WOS:000343907900006
PM 24619651
ER
PT J
AU Ying, TL
Gong, R
Ju, TW
Prabakaran, P
Dimitrov, DS
AF Ying, Tianlei
Gong, Rui
Ju, Tina W.
Prabakaran, Ponraj
Dimitrov, Dimiter S.
TI Engineered Fc based antibody domains and fragments as novel scaffolds
SO BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS
LA English
DT Review
DE Monoclonal antibody; Domain antibody; Antibody engineering; Monomeric
Fc; CH3 domain; CH2 domain
ID HUMAN IGG1; CH2 DOMAINS; INCREASED-STABILITY; CONSTANT DOMAINS;
BINDING-SITE; GAMMA-RIII; B-CELLS; RECEPTOR; THERAPEUTICS; DESIGN
AB Therapeutic monoclonal antibodies (mAbs) have been successful for the therapy of a number of diseases mostly cancer and immune disorders. However, the vast majority of mAbs approved for clinical use are full size, typically in IgG1 format. These mAbs may exhibit relatively poor tissue penetration and restricted epitope access due to their large size. A promising solution to this fundamental limitation is the engineering of smaller scaffolds based on the IgG1 Fc region. These scaffolds can be used for the generation of libraries of mutants from which high-affinity binders can be selected. Comprised of the CH2 and CH3 domains, the Fc region is important not only for the antibody effector function but also for its long half-life. This review focuses on engineered Fc based antibody fragments and domains including native (dimeric) Fc and monomeric Fc as well as CH2 and monomeric CH3, and their use as novel scaffolds and binders. The Fc based binders are promising candidate therapeutics with optimized half-life, enhanced tissue penetration and access to sterically restricted binding sites resulting in an increased therapeutic efficacy. This article is part of a Special Issue entitled: Recent advances in molecular engineering of antibody. Published by Elsevier B.V.
C1 [Ying, Tianlei; Ju, Tina W.; Prabakaran, Ponraj; Dimitrov, Dimiter S.] NCI, Prot Interact Grp, Expt Immunol Lab, Canc & Inflammat Program,NIH, Frederick, MD 21702 USA.
[Gong, Rui] Chinese Acad Sci, Wuhan Inst Virol, Ctr Emerging Infect Dis, Antibody Engn Grp, Wuhan 430071, Hubei, Peoples R China.
[Prabakaran, Ponraj] Frederick Natl Lab Canc Res, Leidos Biomed Res Inc, Basic Sci Program, Frederick, MD 21702 USA.
RP Ying, TL (reprint author), NCI, Prot Interact Grp, Canc & Inflammat Program, NIH, Bldg 567,Room 180, Frederick, MD 21701 USA.
EM tianlei.ying@nih.gov
FU Intramural Research Program of the NIH, National Cancer Institute,
Center for Cancer Research; Federal funds from the NIH, National Cancer
Institute [NO1-CO-12400, HHSN261200800001E]; CRADA; RCT; Wuhan Key
Laboratory on Emerging Infectious Diseases and Biosafety
FX This research was supported by the Intramural Research Program of the
NIH, National Cancer Institute, Center for Cancer Research, and by
Federal funds from the NIH, National Cancer Institute, under contract
numbers NO1-CO-12400 and HHSN261200800001E and CRADA with RCT. We thank
our RCT collaborators Kurt Gehlsen and David Bramhill for useful
discussions and support. We thank the Wuhan Key Laboratory on Emerging
Infectious Diseases and Biosafety for its support. The content of this
publication does not necessarily reflect the views or policies of the
Department of Health and Human Services, nor does the mention of trade
names, commercial products, or organizations imply endorsement by the U.
S. Government.
NR 51
TC 13
Z9 13
U1 1
U2 23
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1570-9639
EI 0006-3002
J9 BBA-PROTEINS PROTEOM
JI BBA-Proteins Proteomics
PD NOV
PY 2014
VL 1844
IS 11
SI SI
BP 1977
EP 1982
DI 10.1016/j.bbapap.2014.04.018
PG 6
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA AR5KR
UT WOS:000343624200011
PM 24792384
ER
PT J
AU Waters, EA
Kincaid, C
Kaufman, AR
Stock, ML
Peterson, LM
Muscanell, NL
Guadagno, RE
AF Waters, Erika A.
Kincaid, Caroline
Kaufman, Annette R.
Stock, Michelle L.
Peterson, Laurel M.
Muscanell, Nicole L.
Guadagno, Rosanna E.
TI Concerns about unintended negative consequences of informing the public
about multifactorial risks may be premature for young adult smokers
SO BRITISH JOURNAL OF HEALTH PSYCHOLOGY
LA English
DT Article
DE tobacco use; smoking; multifactorial; genetic; gene-by-environment;
behaviour; attitudes
ID SMOKING-CESSATION TREATMENT; GENETIC DETERMINISM; MASS-MEDIA;
COMMUNICATIONS REVOLUTION; PERSONALIZED MEDICINE; HEALTH COMMUNICATION;
RANDOMIZED-TRIAL; CANCER CONTROL; DISEASE RISK; GENOMICS
AB BackgroundMany health risks are associated with both genetic and behavioural factors. Concerns have been raised that learning about such multifactorial risks might have detrimental effects on health-related beliefs, cognitions, and affect. However, experimental evidence is sparse.
ObjectiveTo explore the effects of reading an online news article about the discovery of a genetic basis for nicotine addiction.
MethodsSmokers (N=333) were recruited from the psychology subject pools of two major universities. Participants were randomly assigned to read one of three news articles: one describing a genetic basis for nicotine addiction and lung cancer obtained from a national news source, one altered to indicate no genetic basis for nicotine addiction and lung cancer, or one unrelated attention control. Participants then completed an online questionnaire, which assessed smoking-related cognitions and affect, and beliefs about nicotine addiction, quitting smoking, and whether the harms of tobacco use are delayed.
ResultsThere was no statistically significant influence of experimental condition on smoking-related cognitions/affect (ps>.05, (2)<.002), beliefs about addiction and quitting (Wilks' =.98, p=.66, (2)=.01), or delayed harm (ps>.05, (2)<.002).
ConclusionReading an online news article about the presence or absence of a genetic basis for nicotine addiction was not found to change smoking-related cognitions/affect or beliefs among young adult smokers. Concerns about negative effects of multifactorial risk information on health beliefs may be premature. Nevertheless, to effectively translate basic genomics research into effective public health practice, further research should investigate these issues in different populations, via different communication modalities, and for different health outcomes.
C1 [Waters, Erika A.; Kincaid, Caroline] Washington Univ, Sch Med, Dept Surg, Div Publ Hlth Sci, St Louis, MO 63110 USA.
[Kaufman, Annette R.] NCI, Div Canc Control & Populat Sci, Rockville, MD USA.
[Stock, Michelle L.] George Washington Univ, Dept Psychol, Washington, DC 20052 USA.
[Peterson, Laurel M.] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA 15260 USA.
[Muscanell, Nicole L.; Guadagno, Rosanna E.] Univ Alabama, Dept Psychol, Tuscaloosa, AL 35487 USA.
RP Waters, EA (reprint author), Dept Surg, Div Publ Hlth Sci, 660 S Euclid,Campus Box 8100, St Louis, MO 63110 USA.
EM waterse@wudosis.wustl.edu
OI Waters, Erika/0000-0001-7402-0133
FU NIMHD NIH HHS [L60 MD006280]
NR 75
TC 1
Z9 1
U1 1
U2 13
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1359-107X
EI 2044-8287
J9 BRIT J HEALTH PSYCH
JI Br. J. Health Psychol.
PD NOV
PY 2014
VL 19
IS 4
BP 720
EP 736
DI 10.1111/bjhp.12069
PG 17
WC Psychology, Clinical
SC Psychology
GA AR7DB
UT WOS:000343738900004
PM 24118369
ER
PT J
AU Harlow, L
Gochuico, BR
Rosas, IO
Doyle, TJ
Osorio, JC
Travers, TS
Camacho, CC
Oddis, CV
Ascherman, DP
AF Harlow, Lisa
Gochuico, Bernadette R.
Rosas, Ivan O.
Doyle, Tracy J.
Osorio, Juan C.
Travers, Timothy S.
Camacho, Carlos C.
Oddis, Chester V.
Ascherman, Dana P.
TI Anti-citrullinated heat shock protein 90 antibodies identified in
bronchoalveolar lavage fluid are a marker of lung-specific immune
responses
SO CLINICAL IMMUNOLOGY
LA English
DT Article
DE Rheumatoid arthritis; Interstitial lung disease; Bronchoalveolar lavage
fluid; Autoantibodies; HSP90; Citrullination
ID RESOLUTION COMPUTED-TOMOGRAPHY; LONGSTANDING RHEUMATOID-ARTHRITIS;
PULMONARY ALVEOLAR PROTEINOSIS; EXTRAARTICULAR MANIFESTATIONS; DISEASE;
INVOLVEMENT; MORTALITY; ABNORMALITIES
AB Previous work has demonstrated a correlation between serum anti-citrullinated HSP90 antibodies and rheumatoid arthritis-associated interstitial lung disease (RA-ILD). To further investigate this potential pathogenic relationship, we used ELISA-based techniques to assess anti-citrullinated HSP90 antibody profiles in bronchoalveolar lavage fluid (BALE) of patients with different stages of RA-ILD. 9/21 RA-derived BALE specimens demonstrated IgG and/or IgA antibodies targeting citrullinated HSP90 proteins/peptides, highlighting disease specific responses (with a predilection for RA-ILD) that did not occur in IPF patients (0/5) or healthy control subjects (0/5). Comparison of antibody profiles between BALE and matching serum specimens revealed various recognition patterns favoring predominant production of anti-citrullinated HSP90 antibodies within the lung microenvironment-further supporting the connection between this antibody specificity and parenchymal lung disease. Equally important, qualitative as well as quantitative differences in anti-citrullinated HSP90 profiles between BALE and serum indicate that the lung plays a direct role in shaping the immune repertoire of RA/RA-ILD. Published by Elsevier Inc.
C1 [Harlow, Lisa; Ascherman, Dana P.] Univ Miami, Miller Sch Med, Div Rheumatol, Dept Med, Miami, FL 33136 USA.
[Gochuico, Bernadette R.] NIH, Med Genet Branch, NHGR, Bethesda, MD 20892 USA.
[Rosas, Ivan O.; Doyle, Tracy J.; Osorio, Juan C.] Brigham & Womens Hosp, Dept Med, Div Pulm & Crit Care Med, Boston, MA 02115 USA.
[Travers, Timothy S.; Camacho, Carlos C.] Univ Pittsburgh, Sch Med, Dept Computat & Syst Biol, Pittsburgh, PA 15213 USA.
[Oddis, Chester V.] Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA 15213 USA.
RP Ascherman, DP (reprint author), Univ Miami, Miller Sch Med, Div Rheumatol, Dept Med,RMSB, 7152,1600 NW 10th Ave, Miami, FL 33136 USA.
EM DAscherman@med.miami.edu
OI Osorio, Juan C/0000-0001-8090-1551
FU VA Merit Review, ACR/REF Within Our Reach Foundation [1101BX000788]
FX Funding: Dana P. Ascherman: VA Merit Review 1101BX000788, ACR/REF Within
Our Reach Foundation.
NR 29
TC 3
Z9 3
U1 0
U2 7
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1521-6616
EI 1521-7035
J9 CLIN IMMUNOL
JI Clin. Immunol.
PD NOV
PY 2014
VL 155
IS 1
BP 60
EP 70
DI 10.1016/j.clim.2014.08.004
PG 11
WC Immunology
SC Immunology
GA AR5QJ
UT WOS:000343638400009
PM 25150019
ER
PT J
AU Valentin, A
McKinnon, K
Li, JY
Rosati, M
Kulkarni, V
Pilkington, GR
Bear, J
Alicea, C
Vargas-Inchaustegui, DA
Patterson, LJ
Pegu, P
Liyanage, NPM
Gordon, SN
Vaccari, M
Wang, YC
Hogg, AE
Frey, B
Sui, YJ
Reed, SG
Sardesai, NY
Berzofsky, JA
Franchini, G
Robert-Guroff, M
Felber, BK
Pavlakis, GN
AF Valentin, Antonio
McKinnon, Katherine
Li, Jinyao
Rosati, Margherita
Kulkarni, Viraj
Pilkington, Guy R.
Bear, Jenifer
Alicea, Candido
Vargas-Inchaustegui, Diego A.
Patterson, L. Jean
Pegu, Poonam
Liyanage, Namal P. M.
Gordon, Shari N.
Vaccari, Monica
Wang, Yichuan
Hogg, Alison E.
Frey, Blake
Sui, Yongjun
Reed, Steven G.
Sardesai, Niranjan Y.
Berzofsky, Jay A.
Franchini, Genoveffa
Robert-Guroff, Marjorie
Felber, Barbara K.
Pavlakis, George N.
TI Comparative analysis of SIV-specific cellular immune responses induced
by different vaccine platforms in rhesus macaques
SO CLINICAL IMMUNOLOGY
LA English
DT Article
DE Cellular immune response; Prime-boost vaccination; DNA; Protein; Pox
virus ALVAC MVA
ID CD8(+) T-CELLS; IMMUNODEFICIENCY VIRUS-REPLICATION; PREVENT HIV-1
INFECTION; HIGHLY PATHOGENIC SIV; SIMIAN IMMUNODEFICIENCY; SIVMAC251
CHALLENGE; VIRAL LOAD; ENVELOPE PROTEIN; EFFICACY TRIAL; DNA VACCINATION
AB To identify the most promising vaccine candidates for combinatorial strategies, we compared five Sly vaccine platforms including recombinant canary pox virus ALVAC, replication-competent adenovirus type 5 host range mutant RepAd, DNA, modified vaccinia. Ankara (MVA), peptides and protein in distinct combinations. Three regimens used viral vectors (prime or boost) and two regimens used plasmid DNA. Analysis at necropsy showed that the DNA-based vaccine regimens elicited significantly higher cellular responses against Gag and Env than any of the other vaccine platforms. The T cell responses induced by most vaccine regimens disseminated systemically into secondary lymphoid tissues (lymph nodes, spleen) and effector anatomical sites (including liver, vaginal tissue), indicative of their role in viral containment at the portal of entry. The cellular and reported humoral immune response data suggest that combination of DNA and viral vectors elicits a balanced immunity with strong and durable responses able to disseminate into relevant mucosal sites. Published by Elsevier Inc.
C1 [Valentin, Antonio; Li, Jinyao; Rosati, Margherita; Pavlakis, George N.] NCI, Human Retrovirus Sect, Vaccine Branch, Ctr Canc Res,NIH, Frederick, MD 21702 USA.
[McKinnon, Katherine] NCI, FACS Core Facil, Vaccine Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA.
[Kulkarni, Viraj; Pilkington, Guy R.; Bear, Jenifer; Alicea, Candido; Felber, Barbara K.] NCI, Human Retrovirus Pathogenesis Sect, Vaccine Branch, Ctr Canc Res, Frederick, MD 21702 USA.
[Vargas-Inchaustegui, Diego A.; Patterson, L. Jean; Robert-Guroff, Marjorie] NCI, Immune Biol Retroviral Infect Sect, Vaccine Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA.
[Pegu, Poonam; Liyanage, Namal P. M.; Gordon, Shari N.; Vaccari, Monica; Franchini, Genoveffa] NCI, Anim Models & Retroviral Vaccine Sect, Vaccine Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA.
[Wang, Yichuan; Hogg, Alison E.; Frey, Blake; Sui, Yongjun; Berzofsky, Jay A.] NCI, Mol Immunogenet & Vaccine Res Sect, Vaccine Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA.
[Reed, Steven G.] Infect Dis Res Inst, Seattle, WA USA.
[Sardesai, Niranjan Y.] Inovio Pharmaceut Inc, Blue Bell, PA USA.
RP Felber, BK (reprint author), NCI, Vaccine Branch, Ctr Canc Res, POB B,Bldg 535,Rm 210, Frederick, MD 21702 USA.
EM Barbara.felber@nih.gov; george.pavlakis@nih.gov
FU National Cancer Institute, National Institutes of Health (NCI/NIH);
NIH/NIAID/DAIDS under HVDDT [HHSN272200800063C]
FX This work was supported in part by the Intramural Research Program of
the National Cancer Institute, National Institutes of Health (NCI/NIH)
(B.K.F., G.N.P., J.A.B., G.F., M.R.G.) and NIH/NIAID/DAIDS under HVDDT
Contract HHSN272200800063C (NYS). We gratefully acknowledge N. Miller
(NIAID, NIH) for help with gD-env protein expression, J. Tartaglia
(Sanofi Pasteur) for the ALVAC vectors, J. Clements (Tulane University)
for reagents, the animal caretakers and research team at Advanced
BioScience Laboratories, and B. Chowdhury for technical assistance.
NR 77
TC 3
Z9 3
U1 0
U2 4
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1521-6616
EI 1521-7035
J9 CLIN IMMUNOL
JI Clin. Immunol.
PD NOV
PY 2014
VL 155
IS 1
BP 91
EP 107
DI 10.1016/j.clim.2014.09.005
PG 17
WC Immunology
SC Immunology
GA AR5QJ
UT WOS:000343638400013
PM 25229164
ER
PT J
AU Minasian, L
Rosen, O
Auclair, D
Rahman, A
Pazdur, R
Schilsky, RL
AF Minasian, L.
Rosen, O.
Auclair, D.
Rahman, A.
Pazdur, R.
Schilsky, R. L.
TI Optimizing Dosing of Oncology Drugs
SO CLINICAL PHARMACOLOGY & THERAPEUTICS
LA English
DT Review
ID APPROVAL; FOOD; CHEMOTHERAPY; OUTCOMES
AB The purpose of this article is to acknowledge the challenges in optimizing the dosing of oncology drugs and to propose potential approaches to address these challenges in order to optimize effectiveness, minimize toxicity, and promote adherence in patients. These approaches could provide better opportunities to understand the sources of variability in drug exposure and clinical outcomes during the development and premarketing evaluation of investigational new drugs.
C1 [Minasian, L.] NCI, Div Canc Prevent, Bethesda, MD 20892 USA.
[Rosen, O.] Millennium Takeda Oncol Co, Cambridge, MA USA.
[Auclair, D.] Multiple Myeloma Res Fdn, Norwalk, CT USA.
[Rahman, A.; Pazdur, R.] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA.
[Schilsky, R. L.] Amer Soc Clin Oncol, Alexandria, VA 22314 USA.
RP Schilsky, RL (reprint author), Amer Soc Clin Oncol, Alexandria, VA 22314 USA.
EM Richard.Schilsky@asco.org
NR 18
TC 12
Z9 12
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0009-9236
EI 1532-6535
J9 CLIN PHARMACOL THER
JI Clin. Pharmacol. Ther.
PD NOV
PY 2014
VL 96
IS 5
BP 572
EP 579
DI 10.1038/clpt.2014.153
PG 8
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA AR5OE
UT WOS:000343632900018
PM 25105705
ER
PT J
AU Ances, BM
Hammoud, DA
AF Ances, Beau M.
Hammoud, Dima A.
TI Neuroimaging of HIV-associated neurocognitive disorders (HAND)
SO CURRENT OPINION IN HIV AND AIDS
LA English
DT Review
DE diffusion tensor imaging; functional MRI; HIV; neuroimaging; PET;
volumetrics
ID HUMAN-IMMUNODEFICIENCY-VIRUS; POSITRON-EMISSION-TOMOGRAPHY; COMBINATION
ANTIRETROVIRAL THERAPY; PROTEIN 18 KDA; WHITE-MATTER INTEGRITY;
CEREBRAL-BLOOD-FLOW; POSITIVE PATIENTS; BRAIN-INJURY; INFECTED PATIENTS;
FUNCTIONAL MRI
AB Purpose of review
HIV enters the brain after initial infection, and with time can lead to HIV-associated neurocognitive disorders (HAND). Although the introduction of combination antiretroviral therapy has reduced the more severe forms of HAND, milder forms are still highly prevalent. The 'gold standard' for HAND diagnosis remains detailed neuropsychological performance testing but additional biomarkers (including neuroimaging) may assist in early detection of HAND.
Recent findings
We review the application of recently developed noninvasive MRI and PET techniques in HIV+ individuals. In particular, magnetic resonance spectroscopy may be more sensitive than conventional MRI alone in detecting HIV associated changes. Diffusion tensor imaging has become increasingly popular for assessing changes in white matter structural integrity due to HIV. Both functional MRI and PET have been limitedly performed but could provide keys for characterizing neuropathophysiologic changes due to HIV.
Summary
It is hoped that continued progress will allow novel neuroimaging methods to be included in future HAND management guidelines.
C1 [Ances, Beau M.] Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA.
[Ances, Beau M.] Washington Univ, Dept Radiol, St Louis, MO USA.
[Ances, Beau M.] Washington Univ, Dept Biomed Engn, St Louis, MO USA.
[Hammoud, Dima A.] NIH, Ctr Infect Dis Imaging Radiol & Imaging Sci, Ctr Clin, Bethesda, MD 20892 USA.
RP Ances, BM (reprint author), Washington Univ, Sch Med, Dept Neurol, Box 8111,660 South Euclid Ave, St Louis, MO 63110 USA.
EM bances@wustl.edu
RI Hammoud, Dima/C-2286-2015
FU Alzheimer's Association; [R01NR014449]; [R01NR012657]; [R01NR012907];
[R21MH099979]
FX This work was supported by grants R01NR014449, R01NR012657, R01NR012907,
R21MH099979, and the Alzheimer's Association (B.M.A.).
NR 105
TC 10
Z9 11
U1 2
U2 6
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1746-630X
EI 1746-6318
J9 CURR OPIN HIV AIDS
JI Curr. Opin. HIV AIDS
PD NOV
PY 2014
VL 9
IS 6
BP 545
EP 551
DI 10.1097/COH.0000000000000112
PG 7
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA AR0XR
UT WOS:000343298800007
PM 25250553
ER
PT J
AU Johnson, TP
Nath, A
AF Johnson, Tory P.
Nath, Avindra
TI New insights into immune reconstitution inflammatory syndrome of the
central nervous system
SO CURRENT OPINION IN HIV AND AIDS
LA English
DT Review
DE antiretrovirals; brain; encephalitis; HIV-associated neurocognitive
disorders; Tat
ID HIV-INFECTED PATIENTS; IMMUNODEFICIENCY-VIRUS-INFECTION; STARTING
ANTIRETROVIRAL THERAPY; OF-THE-LITERATURE; NEUROCOGNITIVE IMPAIRMENT;
CRYPTOCOCCAL MENINGITIS; CEREBROSPINAL-FLUID; GENERAL-POPULATION;
RISK-FACTORS; AIDS
AB Purpose of review
To highlight the importance of immune reconstitution inflammatory syndrome affecting the brain in HIV-infected individuals in the absence of opportunistic infections. To describe the varied clinical manifestations, unifying pathophysiological features and discuss the principles of management of this syndrome.
Recent findings
Immune reconstitution inflammatory syndrome within the brain is commonly seen in patients with HIV infection upon initiation of antiretroviral drugs. The fulminant forms occur in the face of opportunistic infections or uncontrolled viral replication within the brain. In this case, the enhanced immune response is targeted against the microbial agent, and the brain suffers bystander damage. Treatment requires the combination of the antimicrobial agent, continued antiretrovirals and in some cases corticosteroids. It is increasingly being recognized that despite adequate control of viral replication in the brain, some patients develop a chronic form of T cell encephalitis which appears to be driven by continued production of HIV-Tat protein. In others, the immune response may be targeted against the host antigens in the brain.
Summary
In patients with central nervous system-immune reconstitution inflammatory syndrome, the use of corticosteroids and strategies that prevent T cell migration into the brain may be needed. Extreme caution is necessary if viral eradication strategies are to be employed that involve activation of viral reservoirs, as these patients may be at risk for developing central nervous system-immune reconstitution inflammatory syndrome.
C1 [Johnson, Tory P.; Nath, Avindra] NINDS, Sect Infect Nervous Syst, NIH, Bethesda, MD 20892 USA.
RP Nath, A (reprint author), Bldg 10,7C-103,10 Ctr Dr, Bethesda, MD 20892 USA.
EM natha@ninds.nih.gov
FU National Institute of Neurological Disorders and Stroke, National
Institutes of Health
FX Supported by intramural funds from National Institute of Neurological
Disorders and Stroke, National Institutes of Health.
NR 77
TC 6
Z9 6
U1 1
U2 12
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1746-630X
EI 1746-6318
J9 CURR OPIN HIV AIDS
JI Curr. Opin. HIV AIDS
PD NOV
PY 2014
VL 9
IS 6
BP 572
EP 578
DI 10.1097/COH.0000000000000107
PG 7
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA AR0XR
UT WOS:000343298800011
PM 25275706
ER
PT J
AU Brazhnik, E
Novikov, N
McCoy, AJ
Cruz, AV
Walters, JR
AF Brazhnik, Elena
Novikov, Nikolay
McCoy, Alex J.
Cruz, Ana V.
Walters, Judith R.
TI Functional correlates of exaggerated oscillatory activity in basal
ganglia output in hemiparkinsonian rats
SO EXPERIMENTAL NEUROLOGY
LA English
DT Article
DE Parkinson's disease; Basal ganglia; Substantia nigra pars reticulata;
Beta frequency; Local field potentials; Gait; Motor cortex; Dopamine;
6-Hydroxydopamine; Serotonin; Oscillations
ID DEEP-BRAIN-STIMULATION; EXTERNAL GLOBUS-PALLIDUS; BETA FREQUENCY
SYNCHRONIZATION; LEVODOPA-INDUCED DYSKINESIAS; HUMAN SUBTHALAMIC
NUCLEUS; DOPA-INDUCED DYSKINESIA; ADMINISTERED L-DOPA;
PARKINSONS-DISEASE; NEURONAL DISCHARGE; ACTIVITY PATTERNS
AB Exaggerated beta range (13-30 Hz) synchronized activity is observed in the basal ganglia of Parkinson's disease (PD) patients during implantation of deep brain stimulation electrodes and is thought to contribute to the motor symptoms of this disorder. To explore the translational potential of similar activity observed in a rat model of PD, local field potentials (LFPs) and spiking activity in basal ganglia output were characterized in rats with unilateral dopamine cell lesion during a range of behaviors. A circular treadmill was used to assess activity during walking; hemiparkinsonian rats could maintain a steady gait when oriented ipsiversive to the lesioned hemisphere, but were less effective at walking when oriented contraversive to lesion. Dramatic increases in substantia nigra pars reticulata (SNpr) LFP oscillatory activity and spike-LFP synchronization were observed within the beta/low gamma range (12-40 Hz) in the lesioned hemisphere, relative to the non-lesioned hemisphere, with the dominant frequency of spike-LFP entrainment and LFP power varying with behavioral state. At 3 weeks postlesion, the mean dominant entrainment frequency during ipsiversive treadmill walking and grooming was 34 Hz. Other behaviors were associated with lower mean entrainment frequencies: 27-28 Hz during alert non-walking and REM. 17 Hz during rest and 21 Hz during urethane anesthesia with sensory stimulation. SNpr spike-LFP entrainment frequency was stable during individual treadmill walking epochs, but increased gradually over weeks postlesion. In contrast, SNpr LP power in the 25-40 Hz range was greatest at the initiation of each walking epoch, and decreased during walking to stabilize by 6 min at 49% of initial values. Power was further modulated in conjunction with the 1.5 s stepping rhythm. Administration of L-dopa improved contraversive treadmill walking in correlation with a reduction in SNpr 25-40 Hz LFP power and spike synchronization in the dopamine cell lesioned hemisphere. These effects were reversed by the serotonergic 1A agonist, 8-OH-DPAT. While the prominent spike-LP phase locking observed during ongoing motor activity in the hemiparkinsonian rats occurs at frequencies intriguingly higher than in PD patients, the synchronized activity in the SNpr of this animal model has much in common with oscillatory activity recorded from the basal ganglia of the PD patients. Results support the potential of this model for providing insight into relationships between synchronization of basal ganglia output induced by loss of dopamine and motor symptoms in PD. Published by Elsevier Inc.
C1 [Brazhnik, Elena; Novikov, Nikolay; McCoy, Alex J.; Cruz, Ana V.; Walters, Judith R.] NINDS, Neurophysiol Pharmacol Sect, NIH, Bethesda, MD 20892 USA.
RP Walters, JR (reprint author), NINDS, Neurophysiol Pharmacol Sect, NIH, 35 Convent Dr,Bldg 35 Room 1C905, Bethesda, MD 20892 USA.
EM waltersj@ninds.nih.gov
FU NINDS, NIH
FX The Intramural Research Program of the NINDS, NIH supported this
research. We wish to thank Newlin, Morgan, Tom Talbot and Daryl Brandy
in the Research Services Branch for design and fabrication of the rotary
treadmill.
NR 90
TC 10
Z9 10
U1 1
U2 10
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0014-4886
EI 1090-2430
J9 EXP NEUROL
JI Exp. Neurol.
PD NOV
PY 2014
VL 261
BP 563
EP 577
DI 10.1016/j.expneurol.2014.07.010
PG 15
WC Neurosciences
SC Neurosciences & Neurology
GA AR4AX
UT WOS:000343531500063
PM 25084518
ER
PT J
AU Sultana, A
Nakaya, N
Dong, LJ
Abu-Asab, M
Qian, HH
Tomarev, SI
AF Sultana, Afia
Nakaya, Naoki
Dong, Lijin
Abu-Asab, Mones
Qian, Haohua
Tomarev, Stanislav I.
TI Deletion of olfactomedin 2 induces changes in the AMPA receptor complex
and impairs visual, olfactory, and motor functions in micel
SO EXPERIMENTAL NEUROLOGY
LA English
DT Article
DE Olfactomedin 2; AMPA receptor; Neurobiology; Mouse; Anxiety behavior;
Olfactory defects; Retina
ID OPEN-ANGLE GLAUCOMA; NERVOUS-SYSTEM; GERM-LINE; IN-VIVO; GENE; MYOCILIN;
PROTEINS; MOUSE; MUTATIONS; INTERACTS
AB Olfactomedin 2 (Olfm2) is a secretory glycoprotein belonging to the family of olfactomedin domain-containing proteins. A previous study has shown that a mutation in OLFM2 is associated with primary open angle glaucoma in Japanese patients. In the present study, we generated Olfm2 deficient mice by replacing the Olfm2 gene with the LacZ gene. The loss of Olfm2 resulted in no gross abnormalities. However, Olfm2 null mice showed reduced exploration, locomotion, olfactory sensitivity, abnormal motor coordination, and anxiety related behavior. The pattern of the Olfm2 gene expression was studied in the brain and eye using beta-galactosidase staining. In the brain, Olfm2 was mainly expressed in the olfactory bulb, cortex, piriform cortex, olfactory trabeculae, and inferior and superior colliculus. In the eye expression was detected mainly in retinal ganglion cells. In Olfm2 null mice, the amplitude of the first negative wave in the visual evoked potential test was significantly reduced as compared with wild-type littermates. Olfm2, similar to Olfm1, interacted with the GluR2 subunit of the AMPAR complexes and Olfm2 co-segregated with the AMPA receptor subunit GluR2 and other synaptic proteins in the synaptosomal membrane fraction upon biochemical fractionation of the adult mice cortex and retina. Immunoprecipitation from the synaptosomal membrane fraction of the Olfm2 null mouse brain cortex using the GluR2 antibody showed reduced levels of several components of the AMPAR complex in the immunoprecipitates including Olfm1, PSD95 and CNIH2. These results suggest that heterodimers of Olfm1 and Olfm2 interact with AMPAR more efficiently than Olfm2 homodimers and that Olfm2 plays a role in the organization of the AMPA receptor complexes. Published by Elsevier Inc.
C1 [Sultana, Afia; Nakaya, Naoki; Tomarev, Stanislav I.] NEI, Sect Retinal Gangl Cell Biol, Lab Retinal Cell & Mol Biol, NIH, Bethesda, MD 20892 USA.
[Dong, Lijin] NEI, Genet Engn Facil, NIH, Bethesda, MD 20892 USA.
[Abu-Asab, Mones] NEI, Histopathol Core Facil, NIH, Bethesda, MD 20892 USA.
[Qian, Haohua] NEI, Visual Funct Core, NIH, Bethesda, MD 20892 USA.
RP Tomarev, SI (reprint author), NEI, NIH, Bldg 6,Room 212,6 Ctr Dr, Bethesda, MD 20892 USA.
EM sultanaa@nei.nih.gov; nakayan@nei.nih.gov; Lijin.Dong@nih.gov;
mones@nei.nih.gov; qianh@nei.nih.gov; tomarevs@nei.nih.gov
FU National Eye Institute, National Institutes of Health
FX We thank Yichao Li for his help with ERG and VEP recording. This work
was supported by the Intramural Research Programs of the National Eye
Institute, National Institutes of Health.
NR 41
TC 4
Z9 6
U1 1
U2 5
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0014-4886
EI 1090-2430
J9 EXP NEUROL
JI Exp. Neurol.
PD NOV
PY 2014
VL 261
BP 802
EP 811
DI 10.1016/j.expneurol.2014.09.002
PG 10
WC Neurosciences
SC Neurosciences & Neurology
GA AR4AX
UT WOS:000343531500086
PM 25218043
ER
PT J
AU Liaudet, L
Calderari, B
Pacher, P
AF Liaudet, Lucas
Calderari, Belinda
Pacher, Pal
TI Pathophysiological mechanisms of catecholamine and cocaine-mediated
cardiotoxicity
SO HEART FAILURE REVIEWS
LA English
DT Article
DE Catecholamines; Cocaine; Cardiomyopathy; Oxidative stress; Mitochondria;
Signaling; Heart failure
ID ADRENERGIC-RECEPTOR SUBTYPES; INDUCED CARDIAC DYSFUNCTION; ACUTE
MYOCARDIAL-INFARCTION; (ROS)-INDUCED ROS RELEASE; ACTIVATED
PROTEIN-KINASE; OXIDATIVE STRESS; HEART-FAILURE; PERMEABILITY
TRANSITION; CARDIOMYOCYTE NECROSIS; TARGETED ANTIOXIDANTS
AB Overactivation of the sympatho-adrenergic system is an essential mechanism providing short-term adaptation to the stressful conditions of critical illnesses. In the same way, the administration of exogenous catecholamines is mandatory to support the failing circulation in acutely ill patients. In contrast to these short-term benefits, prolonged adrenergic stress is detrimental to the cardiovascular system by initiating a series of adverse effects triggering significant cardiotoxicity, whose pathophysiological mechanisms are complex and only partially elucidated. In addition to the development of myocardial oxygen supply/demand imbalance induced by the sustained activation of adrenergic receptors, catecholamines can damage cardiomyocytes by fostering mitochondrial dysfunction, via two main mechanisms. The first one is calcium overload, consecutive to beta-adrenergic receptor-mediated activation of protein kinase A and subsequent phosphorylation of multiple Ca2+-cycling proteins. The second one is oxidative stress, primarily related to the transformation of catecholamines into "aminochromes," which undergo redox cycling in mitochondria to generate copious amounts of oxygen-derived free radicals. In turn, calcium overload and oxidative stress promote mitochondrial permeability transition and cardiomyocyte cell death, both via the apoptotic and necrotic pathways. Comparable mechanisms of myocardial toxicity, including marked oxidative stress and mitochondrial dysfunction, have been reported with the use of cocaine, a common recreational drug with potent sympathomimetic activity. The aim of the current review is to present in detail the pathophysiological processes underlying the development of catecholamine and cocaine-induced cardiomyopathy, as such conditions may be frequently encountered in the clinical practice of cardiologists and ICU specialists.
C1 [Liaudet, Lucas; Calderari, Belinda] Univ Hosp Med Ctr, Fac Biol & Med, Dept Intens Care Med, CH-1010 Lausanne, Switzerland.
[Liaudet, Lucas; Calderari, Belinda] Univ Hosp Med Ctr, Fac Biol & Med, Burn Ctr, CH-1010 Lausanne, Switzerland.
[Pacher, Pal] NIAA, Lab Physiol Studies, NIH, Bethesda, MD 20892 USA.
RP Liaudet, L (reprint author), Univ Hosp Med Ctr, Fac Biol & Med, Dept Intens Care Med, BH 08-621, CH-1010 Lausanne, Switzerland.
EM lucas.liaudet@chuv.ch
RI Pacher, Pal/B-6378-2008; Liaudet, Lucas/E-1322-2017
OI Pacher, Pal/0000-0001-7036-8108; Liaudet, Lucas/0000-0003-2670-4930
FU Swiss National Fund for Scientific Research [320000/118174]; NIH/NIAAA
FX This work was supported, in part, by a grant from the Swiss National
Fund for Scientific Research (No. 320000/118174) to LL and by the
Intramural Program of the NIH/NIAAA to PP.
NR 87
TC 16
Z9 17
U1 0
U2 14
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 1382-4147
EI 1573-7322
J9 HEART FAIL REV
JI Heart Fail. Rev.
PD NOV
PY 2014
VL 19
IS 6
BP 815
EP 824
DI 10.1007/s10741-014-9418-y
PG 10
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA AR6XA
UT WOS:000343723000011
PM 24398587
ER
PT J
AU Yano, Y
Ning, HY
Allen, N
Reis, JP
Launer, LJ
Liu, K
Yaffe, K
Greenland, P
Lloyd-Jones, DM
AF Yano, Yuichiro
Ning, Hongyan
Allen, Norrina
Reis, Jared P.
Launer, Lenore J.
Liu, Kiang
Yaffe, Kristine
Greenland, Philip
Lloyd-Jones, Donald M.
TI Long-Term Blood Pressure Variability Throughout Young Adulthood and
Cognitive Function in Midlife The Coronary Artery Risk Development in
Young Adults (CARDIA) Study
SO HYPERTENSION
LA English
DT Article
DE blood pressure; cognition; young adult
ID CARDIOVASCULAR HEALTH; HYPERTENSION; ASSOCIATION; BRAIN; IMPAIRMENT;
AMERICAN; DECLINE; DISEASE; LESIONS
AB Whether long-term blood pressure (BP) variability throughout young adulthood is associated with cognitive function in midlife remains uncertain. Using data from the Coronary Artery Risk Development in Young Adults (CARDIA), which recruited healthy young adults aged 18 to 30 years (mean age, 25 years) at baseline (Y-0), we assessed BP variability by SD and average real variability (ARV) for 25 years (8 visits). Cognitive function was assessed with the Digit Symbol Substitution Test (psychomotor speed test), the Rey Auditory Verbal Learning Test (verbal memory test), and the modified Stroop test (executive function test) at follow-up (Y-25). At the Y-25 examination, participants (n= 2326) had a mean age of 50.4 years, 43% were men, and 40% were black. In multivariable-adjusted linear regression models, higher ARV(SBP), ARV(DBP), and SDDBP were significantly associated with lower scores of Digit Symbol Substitution Test (beta[SE]: -0.025 [0.006], -0.029 [0.007], and -0.029 [0.007], respectively; all P<0.001) and Rey Auditory Verbal Learning Test (beta[SE]: -0.016 [0.006], -0.021 [0.007], and -0.019 [0.007], respectively; all P<0.05) after adjustment for demographic and clinical characteristics and with cumulative exposure to BP through Y-0 to Y-25. Neither SDBP nor ARV(BP) was associated with the Stroop score. The associations between ARV(BP) or SDBP and each cognitive function test were similar between blacks and whites except for 1 significant interaction between race and SDSBP on the Digit Symbol Substitution Test (P<0.05). Long-term BP variability for 25 years beginning in young adulthood was associated with worse psychomotor speed and verbal memory tests in midlife, independent of cumulative exposure to BP during follow-up.
C1 [Yano, Yuichiro; Ning, Hongyan; Allen, Norrina; Liu, Kiang; Greenland, Philip; Lloyd-Jones, Donald M.] Northwestern Univ, Dept Prevent Med, Feinberg Sch Med, Chicago, IL 60611 USA.
[Reis, Jared P.] NHLBI, Div Cardiovasc Sci, Bethesda, MD 20892 USA.
[Launer, Lenore J.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA.
[Yaffe, Kristine] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA.
RP Lloyd-Jones, DM (reprint author), Northwestern Univ, Dept Prevent Med, Feinberg Sch Med, 680 N Lake Shore Dr,Suite 1400, Chicago, IL 60611 USA.
EM dlj@northwestern.edu
FU National Heart, Lung, and Blood Institute (NHLBI); CARDIA Data Analysis
and Publications and Presentations Policies, University of Alabama at
Birmingham [HHSN268201300025C, HHSN268201300026C]; Northwestern
University [HHSN268201300027C]; University of Minnesota
[HHSN268201300028C]; Kaiser Foundation Research Institute
[HHSN268201300029C]; Johns Hopkins University School of Medicine
[HHSN268200900041C]; Intramural Research Program of the National
Institute on Aging (NIA); NIA; NHLBI [AG0005]
FX The Coronary Artery Risk Development in Young Adults Study (CARDIA) is
conducted and supported by the National Heart, Lung, and Blood Institute
(NHLBI) in collaboration with the CARDIA Data Analysis and Publications
and Presentations Policies, University of Alabama at Birmingham
(HHSN268201300025C and HHSN268201300026C), Northwestern University
(HHSN268201300027C), University of Minnesota (HHSN268201300028C), Kaiser
Foundation Research Institute (HHSN268201300029C), and Johns Hopkins
University School of Medicine (HHSN268200900041C). CARDIA is also
partially supported by the Intramural Research Program of the National
Institute on Aging (NIA) and an intra-agency agreement between NIA and
NHLBI (AG0005). This article has been reviewed by CARDIA for scientific
content
NR 24
TC 13
Z9 15
U1 0
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0194-911X
EI 1524-4563
J9 HYPERTENSION
JI Hypertension
PD NOV
PY 2014
VL 64
IS 5
BP 983
EP +
DI 10.1161/HYPERTENSIONAHA.114.03978
PG 22
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA AR4ZB
UT WOS:000343593700015
PM 25156174
ER
PT J
AU Crichton, GE
Elias, MF
Dore, GA
Torres, RV
Robbins, MA
AF Crichton, Georgina E.
Elias, Merrill F.
Dore, Gregory A.
Torres, Rachael V.
Robbins, Michael A.
TI Measurement-to-Measurement Blood Pressure Variability Is Related to
Cognitive Performance The Maine Syracuse Study
SO HYPERTENSION
LA English
DT Article
DE blood pressure; cognition; hypertension
ID CARDIOVASCULAR-DISEASE; EPISODIC HYPERTENSION; VISIT VARIABILITY;
OLDER-ADULTS; ASSOCIATION; BRAIN; AGE; METAANALYSIS; IMPAIRMENT;
DEMENTIA
AB The objective was to investigate the association between variability in blood pressure (BP) and cognitive function for sitting, standing, and reclining BP values and variability derived from all 15 measures. In previous studies, only sitting BP values have been examined, and only a few cognitive measures have been used. A secondary objective was to examine associations between BP variability and cognitive performance in hypertensive individuals stratified by treatment success. Cross-sectional analyses were performed on 972 participants of the Maine Syracuse Study for whom 15 serial BP clinic measures (5 sitting, 5 recumbent, and 5 standing) were obtained before testing of cognitive performance. Using all 15 measures, higher variability in systolic and diastolic BP was associated with poorer performance on multiple measures of cognitive performance, independent of demographic factors, cardiovascular risk factors, and pulse pressure. When sitting, reclining, and standing systolic BP values were compared, only variability in standing BP was related to measures of cognitive performance. However, for diastolic BP, variability in all 3 positions was related to cognitive performance. Mean BP values were weaker predictors of cognition. Furthermore, higher overall variability in both systolic and diastolic BP was associated with poorer cognitive performance in unsuccessfully treated hypertensive individuals (with BP >= 140/90 mm Hg), but these associations were not evident in those with controlled hypertension.
C1 [Crichton, Georgina E.] Univ S Australia, Nutr Physiol Res Ctr, Adelaide, SA 5001, Australia.
[Crichton, Georgina E.] Ctr Rech Publ Sante, Ctr Etud Sante, Strassen, Luxembourg.
[Elias, Merrill F.; Torres, Rachael V.; Robbins, Michael A.] Univ Maine, Dept Psychol, Orono, ME 04469 USA.
[Elias, Merrill F.; Robbins, Michael A.] Univ Maine, Grad Sch Biomed Sci & Engn, Orono, ME USA.
[Dore, Gregory A.] NIA, Behav Epidemiol Sect, Lab Epidemiol & Populat Sci, NIH, Baltimore, MD 21224 USA.
RP Crichton, GE (reprint author), Univ S Australia, Nutr Physiol Res Ctr, GPO Box 2471, Adelaide, SA 5001, Australia.
EM georgina.crichton@mymail.unisa.edu.au
FU National Heart, Lung, and Blood Institute [R01HL67358, R01HL81290];
National Institute on Aging [R01AG03055]; Sidney Sax Research Fellowship
(National Health and Medical Research Council, Australia) [APP1054567];
National Institute on Aging Intramural Research Program
FX This study was supported in part by National Heart, Lung, and Blood
Institute (grant nos. R01HL67358, R01HL81290); by the National Institute
on Aging (grant no. R01AG03055). Dr Crichton was supported by a Sidney
Sax Research Fellowship (National Health and Medical Research Council,
Australia, grant no. APP1054567). Dr Dore was supported by the National
Institute on Aging Intramural Research Program.
NR 39
TC 5
Z9 5
U1 0
U2 7
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0194-911X
EI 1524-4563
J9 HYPERTENSION
JI Hypertension
PD NOV
PY 2014
VL 64
IS 5
BP 1094
EP +
DI 10.1161/HYPERTENSIONAHA.114.04282
PG 10
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA AR4ZB
UT WOS:000343593700030
PM 25156168
ER
PT J
AU Semnani, RT
Moore, V
Bennuru, S
McDonald-Fleming, R
Ganesan, S
Cotton, R
Anuradha, R
Babu, S
Nutman, TB
AF Semnani, Roshanak Tolouei
Moore, Vanessa
Bennuru, Sasisekhar
McDonald-Fleming, Renee
Ganesan, Sundar
Cotton, Rachel
Anuradha, Rajamanickam
Babu, Subash
Nutman, Thomas B.
TI Human Monocyte Subsets at Homeostasis and Their Perturbation in Numbers
and Function in Filarial Infection
SO INFECTION AND IMMUNITY
LA English
DT Article
ID ALTERNATIVE ACTIVATION; PROFILING REVEALS; GENE-EXPRESSION; DENDRITIC
CELLS; MACROPHAGE; DIFFERENTIATION; HETEROGENEITY; REVERSAL
AB To characterize the function and plasticity of the major human circulating monocyte populations and to explore their role in systemic helminth infection, highly purified (by flow-based sorting) human monocyte subsets (CD14(hi)/CD16(neg) [classical], CD14(+ or hi)/CD16(med) [intermediate], and CD14(neg)/CD16(hi) [nonclassical]) were examined at homeostasis and after activation. Among these three subsets the classical and intermediate subsets were found to be the major sources of inflammatory and regulatory cytokines, as well as cytokines/chemokines associated with alternative activation, whereas the nonclassical and classical populations demonstrated an ability to transmigrate through endothelial monolayers. Moreover, it was primarily the classical subset that was the most efficient in promoting autologous T cell proliferation. The distribution of these subsets changed in the context of a systemic helminth (Wuchereria bancrofti) infection such that patent infection altered the frequency and distribution of these monocyte subsets with the nonclassical monocytes being expanded (almost 2-fold) in filarial infection. To understand further the filarial/monocyte interface, in vitro modeling demonstrated that the classical subset internalized filarial antigens more efficiently than the other two subsets but that the parasite-driven regulatory cytokine interleukin-10 was exclusively coming from the intermediate subset. Our data suggest that monocyte subsets have a differential function at homeostasis and in response to helminth parasites.
C1 [Semnani, Roshanak Tolouei; Moore, Vanessa; Bennuru, Sasisekhar; McDonald-Fleming, Renee; Ganesan, Sundar; Cotton, Rachel; Anuradha, Rajamanickam; Babu, Subash; Nutman, Thomas B.] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Semnani, RT (reprint author), NIAID, Parasit Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM rsemnani@niaid.nih.gov
OI Cotton, Rachel/0000-0002-1698-4409
FU Intramural Research Program of the Division of Intramural Research,
NIAID, NIH
FX This study was supported by the Intramural Research Program of the
Division of Intramural Research, NIAID, NIH.
NR 27
TC 1
Z9 1
U1 0
U2 4
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0019-9567
EI 1098-5522
J9 INFECT IMMUN
JI Infect. Immun.
PD NOV
PY 2014
VL 82
IS 11
BP 4438
EP 4446
DI 10.1128/IAI.01973-14
PG 9
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA AR4UQ
UT WOS:000343582900001
ER
PT J
AU Lambert, LH
Bullock, JL
Cook, ST
Miura, K
Garboczi, DN
Diakite, M
Fairhurst, RM
Singh, K
Long, CA
AF Lambert, Lester H.
Bullock, Jeanee L.
Cook, Sharma T.
Miura, Kazutoyo
Garboczi, David N.
Diakite, Mahamadou
Fairhurst, Rick M.
Singh, Kavita
Long, Carole A.
TI Antigen Reversal Identifies Targets of Opsonizing IgGs against
Pregnancy-Associated Malaria
SO INFECTION AND IMMUNITY
LA English
DT Article
ID CHONDROITIN-SULFATE-A; FALCIPARUM-INFECTED ERYTHROCYTES; VARIANT
SURFACE-ANTIGENS; PLASMODIUM-FALCIPARUM; PLACENTAL MALARIA; VACCINE
CANDIDATE; IMMUNOGLOBULIN-G; VAR2CSA PROTEIN; VAR GENE; ANTIBODIES
AB Clinical immunity to pregnancy associated-malaria (PAM) in multigravida women has been attributed to antibodies that recognize VAR2CSA on the infected erythrocyte (IE) surface. The size and complexity of VAR2CSA have focused efforts on selecting one or more of its six Duffy binding-like (DBL) domains for vaccine development. Presently, however, there is no consensus as to which DBL domain(s) would be most effective in eliciting immunity. This is because antibodies to a number of the DBL domains have been found to block the adhesion of VAR2CSA-expressing erythrocytes to chondroitin sulfate A (CSA)-a major criterion for evaluating vaccine candidacy. Opsonization of IEs by cytophilic antibodies that recognize VAR2CSA represents an important yet understudied effector mechanism in acquired immunity to PAM. To date, no studies have sought to determine the targets of those antibodies. In this study, we found that IgGs from multigravida Malian women showed (i) higher reactivity to recombinant DBL domains by enzyme-linked immunosorbent assay (ELISA), (ii) more binding to VAR2CSA-expressing IEs, and (iii) greater opsonization of these IEs by human monocytic cells than IgGs from malaria-exposed Malian men and malaria-naive American adults. Preincubation of IgGs from multigravida women with recombinant DBL2 chi, DBL3 chi, or DBL5 epsilon domains significantly diminished opsonization of VAR2CSA-expressing IEs by human monocytes. These data identify the DBL2 chi, DBL3 chi, and DBL5 epsilon domains as the primary targets of opsonizing IgGs for the first time. Our study introduces a new approach to determining the antigenic targets of opsonizing IgGs in phagocytosis assays.
C1 [Lambert, Lester H.; Miura, Kazutoyo; Fairhurst, Rick M.; Long, Carole A.] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD 20892 USA.
[Bullock, Jeanee L.; Cook, Sharma T.; Garboczi, David N.; Singh, Kavita] NIAID, Res Technol Branch, Struct Biol Sect, NIH, Rockville, MD USA.
[Diakite, Mahamadou] Univ Bamako, Fac Med Pharm & Odontostomatol, Malaria Res & Training Ctr, Bamako, Mali.
RP Long, CA (reprint author), NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD 20892 USA.
EM clong@niaid.nih.gov
FU Intramural Research Program of NIAID, NIH
FX This work was supported by the Intramural Research Program of NIAID,
NIH.
NR 62
TC 6
Z9 7
U1 1
U2 5
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0019-9567
EI 1098-5522
J9 INFECT IMMUN
JI Infect. Immun.
PD NOV
PY 2014
VL 82
IS 11
BP 4842
EP 4853
DI 10.1128/IAI.02097-14
PG 12
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA AR4UQ
UT WOS:000343582900038
PM 25156731
ER
PT J
AU Yahiro, K
Tsutsuki, H
Ogura, K
Nagasawa, S
Moss, J
Noda, M
AF Yahiro, Kinnosuke
Tsutsuki, Hiroyasu
Ogura, Kohei
Nagasawa, Sayaka
Moss, Joel
Noda, Masatoshi
TI DAP1, a Negative Regulator of Autophagy, Controls SubAB-Mediated
Apoptosis and Autophagy
SO INFECTION AND IMMUNITY
LA English
DT Article
ID TOXIGENIC ESCHERICHIA-COLI; CYTOTOXIN INDUCES APOPTOSIS; RETICULUM
CHAPERONE BIP; PORE-FORMING TOXIN; INDUCED CELL-DEATH; SUBTILASE
CYTOTOXIN; SHIGA TOXIN; EPITHELIAL-CELLS; HEME OXYGENASE-1; PROTECTIVE
ROLE
AB Autophagy and apoptosis play critical roles in cellular homeostasis and survival. Subtilase cytotoxin (SubAB), produced by non-O157 type Shiga-toxigenic Escherichia coli (STEC), is an important virulence factor in disease. SubAB, a protease, cleaves a specific site on the endoplasmic reticulum (ER) chaperone protein BiP/GRP78, leading to ER stress, and induces apoptosis. Here we report that in HeLa cells, activation of a PERK (RNA-dependent protein kinase [PKR]-like ER kinase)-eIF2 alpha (alpha subunit of eukaryotic initiation factor 2)-dependent pathway by SubAB-mediated BiP cleavage negatively regulates autophagy and induces apoptosis through death-associated protein 1 (DAP1). We found that SubAB treatment decreased the amounts of autophagy markers LC3-II and p62 as well as those of mTOR (mammalian target of rapamycin) signaling proteins ULK1 and S6K. These proteins showed increased expression levels in PERK knockdown or DAP1 knockdown cells. In addition, depletion of DAP1 in HeLa cells dramatically inhibited the SubAB-stimulated apoptotic pathway: SubAB-induced Bax/Bak conformational changes, Bax/Bak oligomerization, cytochrome c release, activation of caspases, and poly(ADP-ribose) polymerase (PARP) cleavage. These results show that DAP1 is a key regulator, through PERK-eIF2 alpha-dependent pathways, of the induction of apoptosis and reduction of autophagy by SubAB.
C1 [Yahiro, Kinnosuke; Tsutsuki, Hiroyasu; Ogura, Kohei; Nagasawa, Sayaka; Noda, Masatoshi] Chiba Univ, Grad Sch Med, Dept Mol Infectiol, Chiba, Japan.
[Nagasawa, Sayaka] Chiba Univ, Grad Sch Med, Dept Legal Med, Chiba, Japan.
[Moss, Joel] NHLBI, Cardiovasc & Pulm Branch, NIH, Bethesda, MD 20892 USA.
RP Yahiro, K (reprint author), Chiba Univ, Grad Sch Med, Dept Mol Infectiol, Chiba, Japan.
EM yahirok@faculty.chiba-u.jp
FU Ministry of Education, Science and Culture of Japan; Improvement of
Research Environment for Young Researchers program of the Japan Science
and Technology Agency; Ministry of Health, Labour, Welfare of Japan
[H24-Shinkou-Ippan-012]; Takeda Science Foundation; Intramural Research
Program, National Institutes of Health, National Heart, Lung, and Blood
Institute
FX This work was supported by a Grant-in-Aid for Scientific Research from
the Ministry of Education, Science and Culture of Japan and from the
Improvement of Research Environment for Young Researchers program of the
Japan Science and Technology Agency, as well as by grants-in-aid from
the Ministry of Health, Labour, Welfare of Japan (H24-Shinkou-Ippan-012)
and Takeda Science Foundation. Joel Moss was supported by the Intramural
Research Program, National Institutes of Health, National Heart, Lung,
and Blood Institute.
NR 60
TC 5
Z9 5
U1 1
U2 12
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0019-9567
EI 1098-5522
J9 INFECT IMMUN
JI Infect. Immun.
PD NOV
PY 2014
VL 82
IS 11
BP 4899
EP 4908
DI 10.1128/IAI.02213-14
PG 10
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA AR4UQ
UT WOS:000343582900043
PM 25183729
ER
PT J
AU Roth, J
Peer, CJ
Widemann, B
Cole, DE
Ershler, R
Helman, L
Schrump, D
Figg, WD
AF Roth, Jeffrey
Peer, Cody J.
Widemann, Brigitte
Cole, Diane E.
Ershler, Rachel
Helman, Lee
Schrump, David
Figg, William D.
TI Quantitative determination of mithramycin in human plasma by a novel,
sensitive ultra-HPLC-MS/MS method for clinical pharmacokinetic
application
SO JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL
AND LIFE SCIENCES
LA English
DT Article
DE Mithramycin; Ultra-HPLC; Tandem mass spectrometry
ID CANCER-CELLS; COMBINATORIAL BIOSYNTHESIS; APOPTOSIS; PLICAMYCIN;
TOXICITY
AB Mithramycin is a neoplastic antibiotic synthesized by various Streptomyces bacteria. It is under investigation as a chemotherapeutic treatment for a wide variety of cancers. Ongoing and forthcoming clinical trials will require pharmacokinetic analysis of mithramycin in humans, both to see if target concentrations are achieved and to optimize dosing and correlate outcomes (response/toxicity) with pharmacokinetics. Two published methods for mithramycin quantitation exist, but both are immunoassays that lack current bioanalytical standards of selectivity and sensitivity. To provide an upgraded and more widely applicable assay, a UPLC-MS/MS method for quantitation of mithramycin in human plasma was developed. Solid-phase extraction allowed for excellent recoveries (>90%) necessary for high throughput analyses on sensitive instrumentation. However, a similar to 55% reduction in analyte signal was observed as a result of plasma matrix effects. Mithramycin and the internal standard chromomycin were separated on a Waters Acquity BEH C18 column (2.1 x 50 mm, 1.7 mu m) and detected using electrospray ionization operated in the negative mode at mass transitions m/z 1083.5 -> 268.9 and 1181.5 -> 269.0, respectively, on an AB Sciex QTrap 5500. The assay range was 0.5-500 ng/mL and proved to be linear (r(2) > 0.996), accurate (<= 10% deviation), and precise (CV < 15%). Mithramycin was stable in plasma at room temperature for 24h, as well as through three freeze-thaw cycles. This method was subsequently used to quantitate mithramycin plasma concentrations from patients enrolled on two clinical trials at the NCI. Published by Elsevier B.V.
C1 [Roth, Jeffrey; Peer, Cody J.; Figg, William D.] NCI, Clin Pharmacol Program, Bethesda, MD 20892 USA.
[Widemann, Brigitte; Cole, Diane E.; Ershler, Rachel; Helman, Lee] NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA.
[Schrump, David] NCI, Thorac Oncol Branch, Bethesda, MD 20892 USA.
RP Figg, WD (reprint author), Clin Pharmacol Program, 9000 Rockville Pike,Bldg 10,Room 5A01, Bethesda, MD 20892 USA.
EM figgw@helix.nih.gov
RI Figg Sr, William/M-2411-2016
FU National Cancer Institute, National Institutes of Health
FX This study has been funded in whole with federal funds from the National
Cancer Institute, National Institutes of Health.
NR 21
TC 2
Z9 2
U1 0
U2 16
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1570-0232
EI 1873-376X
J9 J CHROMATOGR B
JI J. Chromatogr. B
PD NOV 1
PY 2014
VL 970
BP 95
EP 101
DI 10.1016/j.jchromb.2014.08.021
PG 7
WC Biochemical Research Methods; Chemistry, Analytical
SC Biochemistry & Molecular Biology; Chemistry
GA AR1KE
UT WOS:000343343300013
PM 25247492
ER
PT J
AU Rouse, M
Younes, A
Egan, JM
AF Rouse, Michael
Younes, Antoine
Egan, Josephine M.
TI Resveratrol and curcumin enhance pancreatic beta-cell function by
inhibiting phosphodiesterase activity
SO JOURNAL OF ENDOCRINOLOGY
LA English
DT Article
DE type 2 diabetes; resveratrol; curcumin; phosphodiesterase; beta-cell
ID INSULIN-RESISTANCE; GLUCOSE-INTOLERANCE; METABOLIC SYNDROME; OXIDATIVE
STRESS; MICE; CAMP; DIET; SUPPLEMENTATION; DYSFUNCTION; ANTIOXIDANT
AB Resveratrol (RES) and curcumin (CUR) are polyphenols that are found in fruits and turmeric, and possess medicinal properties that are beneficial in various diseases, such as heart disease, cancer, and type 2 diabetes mellitus (T2DM). Results from recent studies have indicated that their therapeutic properties can be attributed to their anti-inflammatory effects. Owing to reports stating that they protect against beta-cell dysfunction, we studied their mechanism(s) of action in beta-cells. In T2DM, cAMP plays a critical role in glucose- and incretin-stimulated insulin secretion as well as overall pancreatic beta-cell health. A potential therapeutic target in the management of T2DM lies in regulating the activity of phosphodiesterases (PDEs), which degrade cAMP. Both RES and CUR have been reported to act as PDE inhibitors in various cell types, but it remains unknown if they do so in pancreatic beta-cells. In our current study, we found that both RES (0.1-10 mu mol/l) and CUR (1-100 pmol/l)-regulated insulin secretion under glucose- stimulated conditions. Additionally, treating beta-cell lines and human islets with these polyphenols led to increased intracellular cAMP levels in a manner similar to 3-isobutyl-1-methylxanthine, a classic PDE inhibitor. When we investigated the effects of RES and CUR on PDEs, we found that treatment significantly downregulated the mRNA expression of most of the 11 PDE isozymes, including PDE3B, PDE8A, and PDE10A, which have been linked previously to regulation of insulin secretion in islets. Furthermore, RES and CUR inhibited PDE activity in a dose-dependent manner in beta-cell lines and human islets. Collectively, we demonstrate a novel role for natural-occurring polyphenols as PDE inhibitors that enhance pancreatic beta-cell function.
C1 [Rouse, Michael; Egan, Josephine M.] NIA, Clin Invest Lab, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
[Younes, Antoine] NIA, Lab Cardiovasc Sci, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
RP Egan, JM (reprint author), NIA, Clin Invest Lab, Intramural Res Program, NIH, 251 Bayview Blvd, Baltimore, MD 21224 USA.
EM eganj@grc.nia.nih.gov
FU Intramural Research Program of the National Institute on Aging
FX This work was supported by the Intramural Research Program of the
National Institute on Aging.
NR 54
TC 25
Z9 26
U1 2
U2 20
PU BIOSCIENTIFICA LTD
PI BRISTOL
PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT,
ENGLAND
SN 0022-0795
EI 1479-6805
J9 J ENDOCRINOL
JI J. Endocrinol.
PD NOV
PY 2014
VL 223
IS 2
BP 107
EP 117
DI 10.1530/JOE-14-0335
PG 11
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA AR5YT
UT WOS:000343659000005
PM 25297556
ER
PT J
AU Forget, MA
Malu, S
Liu, H
Toth, C
Maiti, S
Kale, C
Haymaker, C
Bernatchez, C
Huls, H
Wang, E
Marincola, FM
Hwu, P
Cooper, LJN
Radvanyi, LG
AF Forget, Marie-Andree
Malu, Shruti
Liu, Hui
Toth, Christopher
Maiti, Sourindra
Kale, Charuta
Haymaker, Cara
Bernatchez, Chantale
Huls, Helen
Wang, Ena
Marincola, Francesco M.
Hwu, Patrick
Cooper, Laurence J. N.
Radvanyi, Laszlo G.
TI Activation and Propagation of Tumor-infiltrating Lymphocytes on
Clinical-grade Designer Artificial Antigen-presenting Cells for Adoptive
Immunotherapy of Melanoma
SO JOURNAL OF IMMUNOTHERAPY
LA English
DT Article
DE adoptive T-cell therapy; tumor-infiltrating lymphocytes; melanoma;
artificial antigen-presenting cells; K562; costimulation
ID B-LINEAGE MALIGNANCIES; CD19-SPECIFIC T-CELLS; METASTATIC MELANOMA;
TRANSFER THERAPY; EFFECTOR FUNCTION; GENE-EXPRESSION; EXPANSION;
FIBRONECTIN; RESPONSES; GROWTH
AB Purpose: Adoptive cell therapy with autologous tumor-infiltrating lymphocytes (TIL) is a therapy for metastatic melanoma with response rates of up to 50%. However, the generation of the TIL transfer product is challenging, requiring pooled allogeneic normal donor peripheral blood mononuclear cells (PBMC) used in vitro as "feeders" to support a rapid-expansion protocol. Here, we optimized a platform to propagate TIL to a clinical scale using K562 cells genetically modified to express costimulatory molecules such as CD86, CD137-ligand, and membrane-bound IL-15 to function as artificial antigen-presenting cells (aAPC) as an alternative to using PBMC feeders.
Experimental Design: We used aAPC or gamma-irradiated PBMC feeders to propagate TIL and measured rates of expansion. The activation and differentiation state was evaluated by flow cytometry and differential gene expression analyses. Clonal diversity was assessed on the basis of the pattern of T-cell receptor usage. T-cell effector function was measured by evaluation of cytotoxic granule content and killing of target cells.
Results: The aAPC propagated TIL at numbers equivalent to that found with PBMC feeders, whereas increasing the frequency of CD8(+) T-cell expansion with a comparable effector-memory phenotype. mRNA profiling revealed an upregulation of genes in the Wnt and stem-cell pathways with the aAPC. The aAPC platform did not skew clonal diversity, and CD8(+) T cells showed comparable antitumor function as those expanded with PBMC feeders.
Conclusions: TIL can be rapidly expanded with aAPC to clinical scale generating T cells with similar phenotypic and effector profiles as with PBMC feeders. These data support the clinical application of aAPC to manufacture TIL for the treatment of melanoma.
C1 [Forget, Marie-Andree; Malu, Shruti; Toth, Christopher; Kale, Charuta; Haymaker, Cara; Bernatchez, Chantale; Hwu, Patrick; Radvanyi, Laszlo G.] Univ Texas MD Anderson Canc Ctr, Dept Melanoma Med Oncol, Houston, TX 77030 USA.
[Forget, Marie-Andree; Maiti, Sourindra; Huls, Helen; Cooper, Laurence J. N.] Univ Texas MD Anderson Canc Ctr, Div Pediat, Houston, TX 77030 USA.
[Liu, Hui; Wang, Ena] NIH, Infect Dis & Immunogenet Sect, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA.
[Liu, Hui; Wang, Ena] NIH, TransNIH Ctr Human Immunol, Bethesda, MD 20892 USA.
[Radvanyi, Laszlo G.] Lion Biotechnol, Woodland Hills, CA 91367 USA.
[Wang, Ena; Marincola, Francesco M.] Sidra Med & Res Hosp, Doha, Qatar.
RP Radvanyi, LG (reprint author), Lion Biotechnol, 21900 Burbank Blvd,3rd Floor, Woodland Hills, CA 91367 USA.
EM laszlo.radvanyi@lionbio.com
FU CPRIT [RP110553-P4]; Adelson Medical Research Foundation (AMRF); Mulva
Foundation; National Institute of Health (NIH) Melanoma SPORE [P50
CA093459-08, R01 CA116206-09]
FX Supported by the CPRIT grant (RP110553-P4) and Marie-Andree Forget
thanks CPRIT for her salary support. The authors would also like to
acknowledge the support provided by the Adelson Medical Research
Foundation (AMRF), and the Mulva Foundation as well as the National
Institute of Health (NIH) Melanoma SPORE (P50 CA093459-08) and the R01
CA116206-09.
NR 49
TC 7
Z9 8
U1 0
U2 15
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1524-9557
EI 1537-4513
J9 J IMMUNOTHER
JI J. Immunother.
PD NOV-DEC
PY 2014
VL 37
IS 9
BP 448
EP 460
PG 13
WC Oncology; Immunology; Medicine, Research & Experimental
SC Oncology; Immunology; Research & Experimental Medicine
GA AR6GQ
UT WOS:000343681700003
PM 25304728
ER
PT J
AU Wiggins, JL
Mitchell, C
Stringaris, A
Leibenluft, E
AF Wiggins, Jillian Lee
Mitchell, Colter
Stringaris, Argyris
Leibenluft, Ellen
TI Developmental Trajectories of Irritability and Bidirectional
Associations With Maternal Depression
SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY
LA English
DT Article
DE irritability; depression; parent; childhood; violence
ID OFFSPRING PSYCHOPATHOLOGY; SYMPTOMS; ADOLESCENCE; INTEGRATION;
DISORDERS; CHILDHOOD; HOSTILITY; BEHAVIOR; VIOLENCE; CHILDREN
AB Objective: Irritability is a dimensional trait in typical development and a common presenting symptom in many psychiatric disorders, including depression. However, little is known about the developmental trajectory of irritability or how child irritability interacts with maternal depression. The present study identifies classes of irritability trajectories from toddlerhood to middle childhood; characterizes maternal depression and other family, social environment, and child variables within each irritability trajectory class; and, as a more exploratory analysis, examines bidirectional associations between maternal depression and child irritability. Method: A total of 4,898 families from the Fragile Families and Child Wellbeing Study reported on irritability symptoms at ages 3, 5, and 9 years, assessed with items from the Child Behavior Checklist. Parental major depressive episode was assessed using the Composite International Diagnostic Interview Short Form at child ages 1, 3, 5, and 9 years. Results: A latent class growth analysis identified 5 irritability classes: low decreasing; moderate decreasing; high steady; initially very high, then decreasing; and high increasing. Children with more severe irritability trajectories are more likely to have mothers with recurrent depression, and, with the exception of the most severe (high increasing irritability) class, were more likely to have mothers who were exposed to violence. Moreover, paternal depression and alcohol abuse, as well as maternal drug and alcohol abuse, were also risk factors for membership in the more severe irritability classes. A latent auto-regressive cross-lag model showed that child irritability at ages 3 and 5 years is associated with increased mother depression at ages 5 and 9, respectively. Conversely, mother depression at child ages 1 and 3 years is associated with increased child irritability at 3 and 5. Conclusion: Irritability development across toddlerhood and middle childhood has 5 main trajectory types, which differ on maternal depression recurrence and exposure to violence. Maternal depression and child irritability influence each other bidirectionally, particularly early in development. Understanding irritability development and its bidirectional relationship with maternal depression and association with violence exposure may help identify intervention targets.
C1 [Wiggins, Jillian Lee; Leibenluft, Ellen] NIMH, Sect Bipolar Spectrum Disorders, Emot & Dev Branch, Bethesda, MD 20892 USA.
[Mitchell, Colter] Univ Michigan, Inst Social Res, Ann Arbor, MI USA.
[Stringaris, Argyris] Kings Coll London, Inst Psychiat, London WC2R 2LS, England.
RP Wiggins, JL (reprint author), NIMH, Sect Bipolar Spectrum Disorders, Emot & Dev Branch, Bldg 15K,MSC-2670, Bethesda, MD 20892 USA.
EM jillian.wiggins@nih.gov
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development (NICHD) [R01HD36916, R01HD39135, R01HD40421]; Fragile
Families and Child Wellbeing Study; NICHD [1R01HD076592-01]; Welcome
Trust; Biomedical-Research Centre of the National Institute of Health
Research; UK Department of Health
FX This study was supported by Eunice Kennedy Shriver National Institute of
Child Health and Human Development (NICHD) grants R01HD36916,
R01HD39135, and R01HD40421, and a consortium of private foundations
support the Fragile Families and Child Wellbeing Study. This study was
also supported by a NICHD grant (C.M.; 1R01HD076592-01) and the Welcome
Trust, Biomedical-Research Centre of the National Institute of Health
Research, UK Department of Health, and royalties from Cambridge
University Press (A.S)
NR 29
TC 11
Z9 11
U1 2
U2 15
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0890-8567
EI 1527-5418
J9 J AM ACAD CHILD PSY
JI J. Am. Acad. Child Adolesc. Psychiatr.
PD NOV
PY 2014
VL 53
IS 11
BP 1191
EP 1205
DI 10.1016/j.jaac.2014.08.005
PG 15
WC Psychology, Developmental; Pediatrics; Psychiatry
SC Psychology; Pediatrics; Psychiatry
GA AR5JG
UT WOS:000343620600008
PM 25440309
ER
PT J
AU Broadbent, AJ
Santos, CP
Godbout, RA
Subbarao, K
AF Broadbent, Andrew J.
Santos, Celia P.
Godbout, Rachel A.
Subbarao, Kanta
TI The Temperature-Sensitive and Attenuation Phenotypes Conferred by
Mutations in the Influenza Virus PB2, PB1, and NP Genes Are Influenced
by the Species of Origin of the PB2 Gene in Reassortant Viruses Derived
from Influenza A/California/07/2009 and A/WSN/33 Viruses
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID A/ANN ARBOR/6/60; AMINO-ACID; A VIRUS; LIVE; VACCINES; REPLICATION;
POLYMERASE; FERRETS; HUMANS; RANGE
AB Live attenuated influenza vaccines in the United States are derived from a human virus that is temperature sensitive (ts), characterized by restricted (>= 100-fold) replication at 39 degrees C. The ts genetic signature (ts sig) has been mapped to 5 loci in 3 genes: PB1 (391E, 581G, and 661T), PB2 (265S), and NP (34G). However, when transferred into avian and swine influenza viruses, only partial ts and attenuation phenotypes occur. To investigate the reason for this, we introduced the ts sig into the human origin virus A/WSN/33 (WSN), the avian-origin virus A/Vietnam/1203/04 (VN04), and the swine origin triple reassortant 2009 pandemic H1N1 virus A/California/07/2009 (CA07), which contains gene segments from human, avian, and swine viruses. The VN04(ts) (sig) and CA07(ts) (sig) viruses replicated efficiently in Madin-Darby canine kidney (MDCK) cells at 39 degrees C, but the replication of WSNts (sig) was restricted >= 100-fold compared to that at 33 degrees C. Reassortant CA07(ts) sig viruses were generated with individual polymerase gene segments from WSN, and vice versa. Only ts sig viruses with a PB2 gene segment derived from WSN were restricted in replication >= 100-fold at 39 degrees C. In ferrets, the CA07(ts) sig virus replicated in the upper and lower respiratory tract, but the replication of a reassortant CA07(ts sig) virus with a WSN PB2 gene was severely restricted in the lungs. Taken together, these data suggest that the origin of the PB2 gene segment influences the ts phenotype in vitro and attenuation in vivo. This could have implications for the design of novel live vaccines against animal origin influenza viruses.
IMPORTANCE
Live attenuated influenza vaccines (LAIVs) on temperature-sensitive (ts) backbones derived from animal origin influenza viruses are being sought for use in the poultry and swine industries and to protect people against animal origin influenza. However, inserting the ts genetic signature from a licensed LAIV backbone fails to fully attenuate these viruses. Our data indicate this is associated with the presence of a PB2 gene segment derived from an avian influenza virus. We show that a reassortant 2009 pandemic H1N1 virus with the ts signature from a licensed LAIV donor virus is ts in vitro and attenuated in vivo when the PB2 gene is derived from a human origin virus but not from an avian virus. Our study provides information that could benefit the rational design of alternative LAIV backbones against animal origin influenza viruses.
C1 [Broadbent, Andrew J.; Santos, Celia P.; Godbout, Rachel A.; Subbarao, Kanta] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Subbarao, K (reprint author), NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
EM ksubbarao@niaid.nih.gov
FU National Institutes of Health (NIH); National Institute of Allergy and
Infectious Diseases (NIAID)
FX This work was supported by the Intramural Research Program of the
National Institutes of Health (NIH) and the National Institute of
Allergy and Infectious Diseases (NIAID).
NR 22
TC 4
Z9 4
U1 3
U2 14
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
EI 1098-5514
J9 J VIROL
JI J. Virol.
PD NOV
PY 2014
VL 88
IS 21
BP 12339
EP 12347
DI 10.1128/JVI.02142-14
PG 9
WC Virology
SC Virology
GA AR1BN
UT WOS:000343314900015
PM 25122786
ER
PT J
AU O'Donnell, CD
Vogel, L
Matsuoka, Y
Jin, H
Subbarao, K
AF O'Donnell, Christopher D.
Vogel, Leatrice
Matsuoka, Yumiko
Jin, Hong
Subbarao, Kanta
TI The Matrix Gene Segment Destabilizes the Acid and Thermal Stability of
the Hemagglutinin of Pandemic Live Attenuated Influenza Virus Vaccines
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID PHASE-I TRIAL; MEMBRANE-FUSION; A VIRUS; HEALTHY-ADULTS; AIRWAY
EPITHELIUM; TEMPERATURE SENSITIVITY; AMANTADINE RESISTANCE; HUMAN
INFECTION; ELEVATED PH; FERRETS
AB The threat of future influenza pandemics and their potential for rapid spread, morbidity, and mortality has led to the development of pandemic vaccines. We generated seven reassortant pandemic live attenuated influenza vaccines (pLAIVs) with the hemagglutinin (HA) and neuraminidase (NA) genes derived from animal influenza viruses on the backbone of the six internal protein gene segments of the temperature sensitive, cold-adapted (ca) A/Ann Arbor/60 (H2N2) virus (AA/60 ca) of the licensed seasonal LAIV. The pLAIV viruses were moderately to highly restricted in replication in seronegative adults; we sought to determine the biological basis for this restriction. Avian influenza viruses generally replicate at higher temperatures than human influenza viruses and, although they shared the same backbone, the pLAIV viruses had a lower shutoff temperature than seasonal LAIV viruses, suggesting that the HA and NA influence the degree of temperature sensitivity. The pH of HA activation of highly pathogenic avian influenza viruses was greater than human and low-pathogenicity avian influenza viruses, as reported by others. However, pLAIV viruses had a consistently higher pH of HA activation and reduced HA thermostability compared to the corresponding wild-type parental viruses. From studies with single-gene reassortant viruses bearing one gene segment from the AA/60 ca virus in recombinant H5N1 or pH1N1 viruses, we found that the lower HA thermal stability and increased pH of HA activation were associated with the AA/60Mgene. Together, the impaired HA acid and thermal stability and temperature sensitivity likely contributed to the restricted replication of the pLAIV viruses we observed in seronegative adults.
IMPORTANCE
There is increasing evidence that the HA stability of influenza viruses depends on the virus strain and host species and that HA stability can influence replication, virulence, and transmission of influenza A viruses in different species. We investigated the HA stability of pandemic live attenuated influenza vaccine (pLAIV) viruses and observed that the pLAIV viruses consistently had a less stable HA than the corresponding wild-type influenza viruses. The reduced HA stability and temperature sensitivity of the pLAIV viruses may account for their restricted replication in clinical trials.
C1 [O'Donnell, Christopher D.; Vogel, Leatrice; Matsuoka, Yumiko; Subbarao, Kanta] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
[Jin, Hong] MedImmune LLC, Mountain View, CA USA.
RP Subbarao, K (reprint author), NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
EM ksubbarao@niaid.nih.gov
FU Intramural Research Program of the NIH, NIAID
FX This research was supported in part by the Intramural Research Program
of the NIH, NIAID.
NR 79
TC 10
Z9 11
U1 0
U2 14
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
EI 1098-5514
J9 J VIROL
JI J. Virol.
PD NOV
PY 2014
VL 88
IS 21
BP 12374
EP 12384
DI 10.1128/JVI.01107-14
PG 11
WC Virology
SC Virology
GA AR1BN
UT WOS:000343314900018
PM 25122789
ER
PT J
AU Brauburger, K
Boehmann, Y
Tsuda, Y
Hoenen, T
Olejnik, J
Schumann, M
Ebihara, H
Muhlberger, E
AF Brauburger, Kristina
Boehmann, Yannik
Tsuda, Yoshimi
Hoenen, Thomas
Olejnik, Judith
Schuemann, Michael
Ebihara, Hideki
Muehlberger, Elke
TI Analysis of the Highly Diverse Gene Borders in Ebola Virus Reveals a
Distinct Mechanism of Transcriptional Regulation
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID RESPIRATORY SYNCYTIAL VIRUS; VESICULAR STOMATITIS-VIRUS; BORNA-DISEASE
VIRUS; G(NS)-L INTERGENIC REGION; RNA START SITES; MESSENGER-RNA;
MARBURG-VIRUS; GENOME ORGANIZATION; MEASLES-VIRUS; SENDAI-VIRUS
AB Ebola virus (EBOV) belongs to the group of nonsegmented negative-sense RNA viruses. The seven EBOV genes are separated by variable gene borders, including short (4- or 5-nucleotide) intergenic regions (IRs), a single long (144-nucleotide) IR, and gene overlaps, where the neighboring gene end and start signals share five conserved nucleotides. The unique structure of the gene overlaps and the presence of a single long IR are conserved among all filoviruses. Here, we sought to determine the impact of the EBOV gene borders during viral transcription. We show that readthrough mRNA synthesis occurs in EBOV-infected cells irrespective of the structure of the gene border, indicating that the gene overlaps do not promote recognition of the gene end signal. However, two consecutive gene end signals at the VP24 gene might improve termination at the VP24-L gene border, ensuring efficient L gene expression. We further demonstrate that the long IR is not essential for but regulates transcription reinitiation in a length-dependent but sequence-independent manner. Mutational analysis of bicistronic minigenomes and recombinant EBOVs showed no direct correlation between IR length and reinitiation rates but demonstrated that specific IR lengths not found naturally in filoviruses profoundly inhibit downstream gene expression. Intriguingly, although truncation of the 144-nucleotide-long IR to 5 nucleotides did not substantially affect EBOV transcription, it led to a significant reduction of viral growth.
IMPORTANCE
Our current understanding of EBOV transcription regulation is limited due to the requirement for high-containment conditions to study this highly pathogenic virus. EBOV is thought to share many mechanistic features with well-analyzed prototype nonsegmented negative-sense RNA viruses. A single polymerase entry site at the 3' end of the genome determines that transcription of the genes is mainly controlled by gene order and cis-acting signals found at the gene borders. Here, we examined the regulatory role of the structurally unique EBOV gene borders during viral transcription. Our data suggest that transcriptional regulation in EBOV is highly complex and differs from that in prototype viruses and further the understanding of this most fundamental process in the filovirus replication cycle. Moreover, our results with recombinant EBOVs suggest a novel role of the long IR found in all filovirus genomes during the viral replication cycle.
C1 [Brauburger, Kristina; Olejnik, Judith; Muehlberger, Elke] Boston Univ, Sch Med, Dept Microbiol, Boston, MA 02118 USA.
[Brauburger, Kristina; Olejnik, Judith; Muehlberger, Elke] Boston Univ, Sch Med, Natl Emerging Infect Dis Labs, Boston, MA 02118 USA.
[Brauburger, Kristina; Boehmann, Yannik; Schuemann, Michael] Univ Marburg, Dept Virol, Marburg, Germany.
[Tsuda, Yoshimi; Hoenen, Thomas; Ebihara, Hideki] NIAID, Virol Lab, Div Intramural Res, NIH, Hamilton, MT USA.
RP Muhlberger, E (reprint author), Boston Univ, Sch Med, Dept Microbiol, Boston, MA 02118 USA.
EM muehlber@bu.edu
OI Hoenen, Thomas/0000-0002-5829-6305
FU NIH [AI057159, 149047-0743, U01-AI082954]; Boston University; Deutsche
Forschungsgemeinschaft [SFB 535]; Cusanuswerk; Intramural Research
Program of the NIH; Intramural Research Program of the NIAID
FX This work was supported by NIH grants AI057159 (New England Regional
Center of Excellence-Kasper, subaward 149047-0743) and U01-AI082954 (to
E.M.), by startup funds from Boston University (to E.M.), by funds from
the Deutsche Forschungsgemeinschaft (SFB 535; to E.M.) and the
Cusanuswerk (to K.B.), and by the Intramural Research Program of the
NIH, NIAID (to Y.T., T.H., and H.E.).
NR 78
TC 7
Z9 7
U1 0
U2 83
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
EI 1098-5514
J9 J VIROL
JI J. Virol.
PD NOV
PY 2014
VL 88
IS 21
BP 12558
EP 12571
DI 10.1128/JVI.01863-14
PG 14
WC Virology
SC Virology
GA AR1BN
UT WOS:000343314900033
PM 25142600
ER
PT J
AU Poole, DS
Yu, SQ
Cai, YY
Dinis, JM
Muller, MA
Jordan, I
Friedrich, TC
Kuhn, JH
Mehle, A
AF Poole, Daniel S.
Yu, Shuiqiong
Cai, Yingyun
Dinis, Jorge M.
Mueller, Marcel A.
Jordan, Ingo
Friedrich, Thomas C.
Kuhn, Jens H.
Mehle, Andrew
TI Influenza A Virus Polymerase Is a Site for Adaptive Changes during
Experimental Evolution in Bat Cells
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID RESPIRATORY SYNDROME CORONAVIRUS; AVIAN H5N1 INFLUENZA; SINGLE
AMINO-ACID; HOST-RANGE; EMERGING VIRUSES; B-VIRUS;
SUBSTRATE-SPECIFICITY; NATURAL RESERVOIR; VIRAL POLYMERASE;
RECEPTOR-BINDING
AB The recent identification of highly divergent influenza A viruses in bats revealed a new, geographically dispersed viral reservoir. To investigate the molecular mechanisms of host-restricted viral tropism and the potential for transmission of viruses between humans and bats, we exposed a panel of cell lines from bats of diverse species to a prototypical human-origin influenza A virus. All of the tested bat cell lines were susceptible to influenza A virus infection. Experimental evolution of human and avian-like viruses in bat cells resulted in efficient replication and created highly cytopathic variants. Deep sequencing of adapted human influenza A virus revealed a mutation in the PA polymerase subunit not previously described, M285K. Recombinant virus with the PA M285K mutation completely phenocopied the adapted virus. Adaptation of an avian virus-like virus resulted in the canonical PB2 E627K mutation that is required for efficient replication in other mammals. None of the adaptive mutations occurred in the gene for viral hemagglutinin, a gene that frequently acquires changes to recognize host-specific variations in sialic acid receptors. We showed that human influenza A virus uses canonical sialic acid receptors to infect bat cells, even though bat influenza A viruses do not appear to use these receptors for virus entry. Our results demonstrate that bats are unique hosts that select for both a novel mutation and a well-known adaptive mutation in the viral polymerase to support replication.
IMPORTANCE
Bats constitute well-known reservoirs for viruses that may be transferred into human populations, sometimes with fatal consequences. Influenza A viruses have recently been identified in bats, dramatically expanding the known host range of this virus. Here we investigated the replication of human influenza A virus in bat cell lines and the barriers that the virus faces in this new host. Human influenza A and B viruses infected cells from geographically and evolutionarily diverse New and Old World bats. Viruses mutated during infections in bat cells, resulting in increased replication and cytopathic effects. These mutations were mapped to the viral polymerase and shown to be solely responsible for adaptation to bat cells. Our data suggest that replication of human influenza A viruses in a nonnative host drives the evolution of new variants and may be an important source of genetic diversity.
C1 [Poole, Daniel S.; Mehle, Andrew] Univ Wisconsin, Dept Med Microbiol & Immunol, Madison, WI 53706 USA.
[Yu, Shuiqiong; Cai, Yingyun; Kuhn, Jens H.] NIAID, NIH, Integrated Res Facil Ft Detrick, Frederick, MD USA.
[Dinis, Jorge M.; Friedrich, Thomas C.] Univ Wisconsin, Sch Vet Med, Dept Pathobiol Sci, Madison, WI 53706 USA.
[Mueller, Marcel A.] Univ Bonn, Inst Virol, Bonn, Germany.
[Jordan, Ingo] ProBioGen AG, Berlin, Germany.
[Friedrich, Thomas C.] Wisconsin Natl Primate Res Ctr, Madison, WI USA.
RP Mehle, A (reprint author), Univ Wisconsin, Dept Med Microbiol & Immunol, Madison, WI 53706 USA.
EM amehle@wisc.edu
RI Kuhn, Jens H./B-7615-2011;
OI Kuhn, Jens H./0000-0002-7800-6045; Jordan, Ingo/0000-0003-2711-7252;
Mueller, Marcel/0000-0003-2242-5117
FU National Institute of General Medical Sciences [R00GM088484]; Shaw
Scientist Award; Mirus Research Award; Wisconsin Partnership Education
and Research Committee New Investigator Program grant [2563]
FX This work was supported in part by the National Institute of General
Medical Sciences (R00GM088484), a Shaw Scientist Award, a Mirus Research
Award, and a Wisconsin Partnership Education and Research Committee New
Investigator Program grant (grant 2563) to A.M.
NR 101
TC 9
Z9 9
U1 2
U2 18
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
EI 1098-5514
J9 J VIROL
JI J. Virol.
PD NOV
PY 2014
VL 88
IS 21
BP 12572
EP 12585
DI 10.1128/JVI.01857-14
PG 14
WC Virology
SC Virology
GA AR1BN
UT WOS:000343314900034
PM 25142579
ER
PT J
AU Hraber, P
Korber, BT
Lapedes, AS
Bailer, RT
Seaman, MS
Gao, H
Greene, KM
McCutchan, F
Williamson, C
Kim, JH
Tovanabutra, S
Hahn, BH
Swanstrom, R
Thomson, MM
Gao, F
Harris, L
Giorgi, E
Hengartner, N
Bhattacharya, T
Mascola, JR
Montefiori, DC
AF Hraber, Peter
Korber, Bette T.
Lapedes, Alan S.
Bailer, Robert T.
Seaman, Michael S.
Gao, Hongmei
Greene, Kelli M.
McCutchan, Francine
Williamson, Carolyn
Kim, Jerome H.
Tovanabutra, Sodsai
Hahn, Beatrice H.
Swanstrom, Ronald
Thomson, Michael M.
Gao, Feng
Harris, Linda
Giorgi, Elena
Hengartner, Nicholas
Bhattacharya, Tanmoy
Mascola, John R.
Montefiori, David C.
TI Impact of Clade, Geography, and Age of the Epidemic on HIV-1
Neutralization by Antibodies
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID IMMUNODEFICIENCY-VIRUS TYPE-1; INJECTION-DRUG USERS; B-CELL RECEPTORS;
EFFICACY TRIAL; ENVELOPE GLYCOPROTEINS; VACCINE DEVELOPMENT; IMMUNOGEN
DESIGN; STRUCTURAL BASIS; FOUNDER VIRUS; ENV CLONES
AB Neutralizing antibodies (nAbs) are a high priority for vaccines that aim to prevent the acquisition of HIV-1 infection. Vaccine effectiveness will depend on the extent to which induced antibodies neutralize the global diversity of circulating HIV-1 variants. Using large panels of genetically and geographically diverse HIV-1 Env-pseudotyped viruses and chronic infection plasma samples, we unambiguously show that cross-clade nAb responses are commonly induced in response to infection by any virus clade. Nonetheless, neutralization was significantly greater when the plasma clade matched the clade of the virus being tested. This within-clade advantage was diminished in older, more-diverse epidemics in southern Africa, the United States, and Europe compared to more recent epidemics in Asia. It was most pronounced for circulating recombinant form (CRF) 07_BC, which is common in China and is the least-divergent lineage studied; this was followed by the slightly more diverse Asian CRF01_AE. We found no evidence that transmitted/founder viruses are generally more susceptible to neutralization and are therefore easier targets for vaccination than chronic viruses. Features of the gp120 V1V2 loop, in particular, length, net charge, and number of N-linked glycans, were associated with Env susceptibility and plasma neutralization potency in a manner consistent with neutralization escape being a force that drives viral diversification and plasma neutralization breadth. The overall susceptibility of Envs and potencies of plasma samples were highly predictive of the neutralization outcome of any single virus-plasma combination. These findings highlight important considerations for the design and testing of candidate HIV-1 vaccines that aim to elicit effective nAbs.
IMPORTANCE An effective HIV-1 vaccine will need to overcome the extraordinary variability of the virus, which is most pronounced in the envelope glycoproteins (Env), which are the sole targets for neutralizing antibodies (nAbs). Distinct genetic lineages, or clades, of HIV-1 occur in different locales that may require special consideration when designing and testing vaccines candidates. We show that nAb responses to HIV-1 infection are generally active across clades but are most potent within clades. Because effective vaccine-induced nAbs are likely to share these properties, optimal coverage of a particular clade or combination of clades may require clade-matched immunogens. Optimal within-clade coverage might be easier to achieve in regions such as China and Thailand, where the epidemic is more recent and the virus less diverse than in southern Africa, the United States, and Europe. Finally, features of the first and second hypervariable regions of gp120 (V1V2) may be critical for optimal vaccine design.
C1 [Hraber, Peter; Korber, Bette T.; Lapedes, Alan S.; Giorgi, Elena; Hengartner, Nicholas; Bhattacharya, Tanmoy] Los Alamos Natl Lab, Los Alamos, NM 87544 USA.
[Korber, Bette T.] New Mexico Consortium, Los Alamos, NM USA.
[Bailer, Robert T.; Mascola, John R.] NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA.
[Seaman, Michael S.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
[Gao, Hongmei; Greene, Kelli M.; Gao, Feng; Montefiori, David C.] Duke Univ, Med Ctr, Durham, NC USA.
[McCutchan, Francine; Kim, Jerome H.; Tovanabutra, Sodsai] Walter Reed Army Inst Res, US Mil HIV Res Program, Silver Spring, MD USA.
[Williamson, Carolyn] Univ Cape Town, Inst Infect Dis & Mol Med, ZA-7925 Cape Town, South Africa.
[Hahn, Beatrice H.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Swanstrom, Ronald] Univ N Carolina, Dept Microbiol & Immunol, Chapel Hill, NC USA.
[Thomson, Michael M.] Inst Salud Carlos III, Ctr Nacl Microbiol, Madrid, Spain.
[Harris, Linda] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
[Bhattacharya, Tanmoy] Santa Fe Inst, Santa Fe, NM 87501 USA.
RP Montefiori, DC (reprint author), Los Alamos Natl Lab, Los Alamos, NM 87544 USA.
EM david.montefiori@duke.edu
RI Bhattacharya, Tanmoy/J-8956-2013;
OI Bhattacharya, Tanmoy/0000-0002-1060-652X; , Carolyn/0000-0003-0125-1226;
Korber, Bette/0000-0002-2026-5757; Hraber, Peter/0000-0002-2920-4897
FU Bill & Melinda Gates Foundation [38619, 1032144]
FX This work was funded by grants from the Bill & Melinda Gates Foundation,
which established the Comprehensive Antibody Vaccine Immune Monitoring
Consortium as part of the Collaboration for AIDS Vaccine Discovery
(grants 38619 and 1032144).
NR 111
TC 18
Z9 18
U1 1
U2 7
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
EI 1098-5514
J9 J VIROL
JI J. Virol.
PD NOV
PY 2014
VL 88
IS 21
BP 12623
EP 12643
DI 10.1128/JVI.01705-14
PG 21
WC Virology
SC Virology
GA AR1BN
UT WOS:000343314900038
PM 25142591
ER
PT J
AU Rudicell, RS
Do Kwon, Y
Ko, SY
Pegu, A
Louder, MK
Georgiev, IS
Wu, XL
Zhu, J
Boyington, JC
Chen, XJ
Shi, W
Yang, ZY
Doria-Rose, NA
McKee, K
O'Dell, S
Schmidt, SD
Chuang, GY
Druz, A
Soto, C
Yang, YP
Zhang, BS
Zhou, TQ
Todd, JP
Lloyd, KE
Eudailey, J
Roberts, KE
Donald, BR
Bailer, RT
Ledgerwood, J
Mullikin, JC
Shapiro, L
Koup, RA
Graham, BS
Nason, MC
Connors, M
Haynes, BF
Rao, SS
Roederer, M
Kwong, PD
Mascola, JR
Nabel, GJ
AF Rudicell, Rebecca S.
Do Kwon, Young
Ko, Sung-Youl
Pegu, Amarendra
Louder, Mark K.
Georgiev, Ivelin S.
Wu, Xueling
Zhu, Jiang
Boyington, Jeffrey C.
Chen, Xuejun
Shi, Wei
Yang, Zhi-Yong
Doria-Rose, Nicole A.
McKee, Krisha
O'Dell, Sijy
Schmidt, Stephen D.
Chuang, Gwo-Yu
Druz, Aliaksandr
Soto, Cinque
Yang, Yongping
Zhang, Baoshan
Zhou, Tongqing
Todd, John-Paul
Lloyd, Krissey E.
Eudailey, Joshua
Roberts, Kyle E.
Donald, Bruce R.
Bailer, Robert T.
Ledgerwood, Julie
Mullikin, James C.
Shapiro, Lawrence
Koup, Richard A.
Graham, Barney S.
Nason, Martha C.
Connors, Mark
Haynes, Barton F.
Rao, Srinivas S.
Roederer, Mario
Kwong, Peter D.
Mascola, John R.
Nabel, Gary J.
CA NISC Comparative Sequencing Progra
TI Enhanced Potency of a Broadly Neutralizing HIV-1 Antibody In Vitro
Improves Protection against Lentiviral Infection In Vivo
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID IMMUNODEFICIENCY-VIRUS TYPE-1; HUMAN MONOCLONAL-ANTIBODIES; MUCOSAL SHIV
CHALLENGE; N-GLYCAN RECOGNITION; ENVELOPE GLYCOPROTEIN; STRUCTURAL
BASIS; HUMANIZED MICE; VACCINE DEVELOPMENT; VAGINAL CHALLENGE; DEPENDENT
EPITOPE
AB Over the past 5 years, a new generation of highly potent and broadly neutralizing HIV-1 antibodies has been identified. These antibodies can protect against lentiviral infection in nonhuman primates (NHPs), suggesting that passive antibody transfer would prevent HIV-1 transmission in humans. To increase the protective efficacy of such monoclonal antibodies, we employed next-generation sequencing, computational bioinformatics, and structure-guided design to enhance the neutralization potency and breadth of VRC01, an antibody that targets the CD4 binding site of the HIV-1 envelope. One variant, VRC07-523, was 5- to 8-fold more potent than VRC01, neutralized 96% of viruses tested, and displayed minimal autoreactivity. To compare its protective efficacy to that of VRC01 in vivo, we performed a series of simian-human immunodeficiency virus (SHIV) challenge experiments in nonhuman primates and calculated the doses of VRC07-523 and VRC01 that provide 50% protection (EC50). VRC07-523 prevented infection in NHPs at a 5-fold lower concentration than VRC01. These results suggest that increased neutralization potency in vitro correlates with improved protection against infection in vivo, documenting the improved functional efficacy of VRC07-523 and its potential clinical relevance for protecting against HIV-1 infection in humans.
IMPORTANCE
In the absence of an effective HIV-1 vaccine, alternative strategies are needed to block HIV-1 transmission. Direct administration of HIV-1-neutralizing antibodies may be able to prevent HIV-1 infections in humans. This approach could be especially useful in individuals at high risk for contracting HIV-1 and could be used together with antiretroviral drugs to prevent infection. To optimize the chance of success, such antibodies can be modified to improve their potency, breadth, and in vivo half-life. Here, knowledge of the structure of a potent neutralizing antibody, VRC01, that targets the CD4-binding site of the HIV-1 envelope protein was used to engineer a next-generation antibody with 5- to 8-fold increased potency in vitro. When administered to nonhuman primates, this antibody conferred protection at a 5-fold lower concentration than the original antibody. Our studies demonstrate an important correlation between in vitro assays used to evaluate the therapeutic potential of antibodies and their in vivo effectiveness.
C1 [Rudicell, Rebecca S.; Do Kwon, Young; Ko, Sung-Youl; Pegu, Amarendra; Louder, Mark K.; Georgiev, Ivelin S.; Wu, Xueling; Zhu, Jiang; Boyington, Jeffrey C.; Chen, Xuejun; Shi, Wei; Yang, Zhi-Yong; Doria-Rose, Nicole A.; McKee, Krisha; O'Dell, Sijy; Schmidt, Stephen D.; Chuang, Gwo-Yu; Druz, Aliaksandr; Soto, Cinque; Yang, Yongping; Zhang, Baoshan; Zhou, Tongqing; Todd, John-Paul; Bailer, Robert T.; Ledgerwood, Julie; Shapiro, Lawrence; Koup, Richard A.; Graham, Barney S.; Rao, Srinivas S.; Roederer, Mario; Kwong, Peter D.; Mascola, John R.; Nabel, Gary J.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Lloyd, Krissey E.; Eudailey, Joshua; Haynes, Barton F.] Duke Univ, Med Ctr, Duke Human Vaccine Inst, Durham, NC USA.
[Roberts, Kyle E.; Donald, Bruce R.] Duke Univ, Dept Comp Sci, Durham, NC 27706 USA.
[Donald, Bruce R.] Duke Univ, Med Ctr, Dept Biochem, Durham, NC 27710 USA.
[Mullikin, James C.; NISC Comparative Sequencing Progra] NHGRI, NIH Intramural Sequencing Ctr, NIH, Bethesda, MD 20892 USA.
[Shapiro, Lawrence] Columbia Univ, Dept Biochem & Mol Biophys, New York, NY USA.
[Nason, Martha C.] NIAID, Biostat Res Branch, NIH, Bethesda, MD 20892 USA.
[Connors, Mark] NIAID, HIV Specif Immun Sect, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA.
RP Mascola, JR (reprint author), NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM jmascola@nih.gov; gary.nabel@sanofi.com
RI Kwon, Young Do/A-6957-2010; Zhou, Tongqing/A-6880-2010; Schmidt,
Stephen/B-5398-2012;
OI Zhou, Tongqing/0000-0002-3935-4637; Pegu, Amarendra/0000-0003-3564-6453
FU Intramural Research Program of the VRC, NIAID, NIH; Foundation for the
National Institutes of Health; Collaboration for AIDS Vaccine Discovery
(CAVD); Bill & Melinda Gates Foundation [OPP1039775]; NIH [R01 GM78031];
U.S. Department of Energy, Basic Energy Sciences, Office of Science
[W-31-109-Eng-38]
FX Support for this work was provided by the Intramural Research Program of
the VRC, NIAID, NIH. Additionally, this research has been supported in
part by a grant from the Foundation for the National Institutes of
Health with support from the Collaboration for AIDS Vaccine Discovery
(CAVD) award OPP1039775 from the Bill & Melinda Gates Foundation. B.R.D.
and K.E.R. were supported by NIH grant R01 GM78031 (to B.R.D.).; Use of
sector 22 (Southeast Region Collaborative Access team) at the Advanced
Photon Source was supported by the U.S. Department of Energy, Basic
Energy Sciences, Office of Science, under contract number
W-31-109-Eng-38.
NR 87
TC 60
Z9 60
U1 2
U2 21
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
EI 1098-5514
J9 J VIROL
JI J. Virol.
PD NOV
PY 2014
VL 88
IS 21
BP 12669
EP 12682
DI 10.1128/JVI.02213-14
PG 14
WC Virology
SC Virology
GA AR1BN
UT WOS:000343314900041
PM 25142607
ER
PT J
AU Streeck, H
Lu, R
Beckwith, N
Milazzo, M
Liu, M
Routy, JP
Little, S
Jessen, H
Kelleher, AD
Hecht, F
Sekaly, RP
Alter, G
Heckerman, D
Carrington, M
Rosenberg, ES
Altfeld, M
AF Streeck, Hendrik
Lu, Richard
Beckwith, Noor
Milazzo, Mark
Liu, Michelle
Routy, Jean-Pierre
Little, Susan
Jessen, Heiko
Kelleher, Anthony D.
Hecht, Frederick
Sekaly, Rafick-Pierre
Alter, Galit
Heckerman, David
Carrington, Mary
Rosenberg, Eric S.
Altfeld, Marcus
TI Emergence of Individual HIV-Specific CD8 T Cell Responses during Primary
HIV-1 Infection Can Determine Long-Term Disease Outcome
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; VIRAL LOAD; LYMPHOCYTE ESCAPE; TYPE-1
INFECTION; SET-POINT; AIDS; PROGRESSION; VIREMIA; EPITOPE; GAG
AB Events during primary HIV-1 infection have been shown to be critical for the subsequent rate of disease progression. Early control of viral replication, resolution of clinical symptoms and development of a viral set point have been associated with the emergence of HIV-specific CD8 T cell responses. Here we assessed which particular HIV-specific CD8 T cell responses contribute to long-term control of HIV-1. A total of 620 individuals with primary HIV-1 infection were screened by gamma interferon (IFN-gamma) enzyme-linked immunospot (ELISPOT) assay for HLA class I-restricted, epitope-specific CD8 T cell responses using optimally defined epitopes approximately 2 months after initial presentation. The cohort was predominantly male (97%) and Caucasian (83%) (Fiebig stages II/III [n = 157], IV [n = 64], V [n = 286], and VI [n = 88] and Fiebig stage not determined [n = 25]). Longitudinal viral loads, CD4 count, and time to ART were collected for all patients. We observed strong associations between viral load at baseline (initial viremia) and the established early viral set points (P < 0.0001). Both were significantly associated with HLA class I genotypes (P = 0.0009). While neither the breadth nor the magnitude of HIV-specific CD8 T cell responses showed an influence on the early viral set point, a broader HIV-specific CD8 T cell response targeting epitopes within HIV-1 Gag during primary HIV-1 infection was associated with slower disease progression. Moreover, the induction of certain HIV-specific CD8 T cell responses-but not others-significantly influenced the time to ART initiation. Individual epitope-specific CD8 T cell responses contribute significantly to HIV-1 disease control, demonstrating that the specificity of the initial HIV-specific CD8 T cell response rather than the restricting HLA class I molecule alone is a critical determinant of antiviral function.
IMPORTANCE
Understanding which factors are involved in the control of HIV-1 infection is critical for the design of therapeutic strategies for patients living with HIV/AIDS. Here, using a cohort of over 600 individuals with acute and early HIV-1 infection, we assessed in unprecedented detail the individual contribution of epitope-specific CD8 T cell responses directed against HIV-1 to control of viremia and their impact on the overall course of disease progression.
C1 [Streeck, Hendrik; Lu, Richard; Milazzo, Mark; Liu, Michelle] Walter Reed Army Inst Res, US Mil HIV Res Program, Silver Spring, MD 20910 USA.
[Streeck, Hendrik; Lu, Richard; Milazzo, Mark; Liu, Michelle] Henry M Jackson Fdn Adv Mil Med, Bethesda, MD USA.
[Streeck, Hendrik; Alter, Galit; Carrington, Mary; Altfeld, Marcus] Ragon Inst MGH MIT & Harvard, Cambridge, MA 02139 USA.
[Beckwith, Noor] Harvard Univ, Sch Med, Boston, MA USA.
[Routy, Jean-Pierre] McGill Univ, Div Hematol, Montreal, PQ, Canada.
[Routy, Jean-Pierre] McGill Univ, Royal Victoria Hosp, Immunodeficiency Serv, Montreal, PQ H3A 1A1, Canada.
[Little, Susan] Univ Calif San Diego, Dept Med, San Diego, CA 92103 USA.
[Jessen, Heiko] HIV Clin Praxis Jessen, Berlin, Germany.
[Kelleher, Anthony D.] UNSW, Kirby Inst, Sydney, NSW, Australia.
[Hecht, Frederick] Univ Calif San Francisco, Dept Med, San Francisco Gen Hosp, San Francisco, CA USA.
[Sekaly, Rafick-Pierre] Vaccine & Gene Therapy Inst Florida, Div Infect Dis, Port St Lucie, FL USA.
[Heckerman, David] Microsoft Res, eSci Grp, Los Angeles, CA USA.
[Carrington, Mary] Leidos Biomedical Res Inc, Frederick Natl Lab Canc Res, Expt Immunol Lab, Canc & Inflammat Program, Frederick, MD USA.
[Rosenberg, Eric S.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Altfeld, Marcus] Heinrich Pette Inst, Hamburg, Germany.
RP Streeck, H (reprint author), Walter Reed Army Inst Res, US Mil HIV Res Program, Silver Spring, MD 20910 USA.
EM hstreeck@hivresearch.org
OI Beckwith, Noor/0000-0001-6025-8642
FU NIH [P01 AI074415]; CIHR CTN/HIV trial network [CTN 247]; FRQ-S
SIDA/maladies infectieuses; U.S. National Institutes of Health (NIH)
[R01 AI091450-01, R01 AI094602-01]; Henry M. Jackson Foundation for the
Advancement of Military Medicine, Inc. [W81XWH-11-2-0174]; U.S.
Department of Defense (DOD); Frederick National Laboratory for Cancer
Research [HHSN261200800001E]; Intramural Research Program of the NIH,
Frederick National Lab, Center for Cancer Research
FX This study was supported in part by NIH P01 AI074415 and in part by CIHR
CTN/HIV trial network (CTN 247) and FRQ-S SIDA/maladies infectieuses. H.
S. is funded by the U.S. National Institutes of Health (NIH) (R01
AI091450-01 and R01 AI094602-01) and a cooperative agreement
(W81XWH-11-2-0174) between the Henry M. Jackson Foundation for the
Advancement of Military Medicine, Inc., and the U.S. Department of
Defense (DOD). This project was also funded in whole or in part by
federal funds from the Frederick National Laboratory for Cancer
Research, under contract no. HHSN261200800001E. This research was
supported in part by the Intramural Research Program of the NIH,
Frederick National Lab, Center for Cancer Research.
NR 31
TC 7
Z9 7
U1 0
U2 9
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
EI 1098-5514
J9 J VIROL
JI J. Virol.
PD NOV
PY 2014
VL 88
IS 21
BP 12793
EP 12801
DI 10.1128/JVI.02016-14
PG 9
WC Virology
SC Virology
GA AR1BN
UT WOS:000343314900051
PM 25165102
ER
PT J
AU Acharya, P
Tolbert, WD
Gohain, N
Wu, XJ
Yu, L
Liu, TY
Huang, WS
Huang, CC
Do Kwon, Y
Louder, RK
Luongo, TS
McLellan, JS
Pancera, M
Yang, YP
Zhang, BS
Flinko, R
Foulke, JS
Sajadi, MM
Kamin-Lewis, R
Robinson, JE
Martin, L
Kwong, PD
Guan, YJ
DeVico, AL
Lewis, GK
Pazgier, M
AF Acharya, Priyamvada
Tolbert, William D.
Gohain, Neelakshi
Wu, Xueji
Yu, Lei
Liu, Tongyun
Huang, Wensheng
Huang, Chih-chin
Do Kwon, Young
Louder, Robert K.
Luongo, Timothy S.
McLellan, Jason S.
Pancera, Marie
Yang, Yongping
Zhang, Baoshan
Flinko, Robin
Foulke, James S., Jr.
Sajadi, Mohammad M.
Kamin-Lewis, Roberta
Robinson, James E.
Martin, Loic
Kwong, Peter D.
Guan, Yongjun
DeVico, Anthony L.
Lewis, George K.
Pazgier, Marzena
TI Structural Definition of an Antibody-Dependent Cellular Cytotoxicity
Response Implicated in Reduced Risk for HIV-1 Infection
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID SIMIAN IMMUNODEFICIENCY VIRUS; NEUTRALIZATION IN-VITRO; VAGINAL SHIV
CHALLENGE; VACCINE EFFICACY TRIAL; GP120 INNER DOMAIN; MEDIATED
CYTOTOXICITY; ENVELOPE GLYCOPROTEIN; MONOCLONAL-ANTIBODIES; EFFECTOR
FUNCTION; CONFORMATIONAL TRANSITIONS
AB The RV144 vaccine trial implicated epitopes in the C1 region of gp120 (A32-like epitopes) as targets of potentially protective antibody-dependent cellular cytotoxicity (ADCC) responses. A32-like epitopes are highly immunogenic, as infected or vaccinated individuals frequently produce antibodies specific for these determinants. Antibody titers, as measured by enzyme-linked immunosorbent assay (ELISA) against these epitopes, however, do not consistently correlate with protection. Here, we report crystal structures of CD4-stabilized gp120 cores complexed with the Fab fragments of two nonneutralizing, A32-like monoclonal antibodies (MAbs), N5-i5 and 2.2c, that compete for antigen binding and have similar antigen-binding affinities yet exhibit a 75-fold difference in ADCC potency. We find that these MAbs recognize overlapping epitopes formed by mobile layers 1 and 2 of the gp120 inner domain, including the C1 and C2 regions, but bind gp120 at different angles via juxtaposed V-H and V-L contact surfaces. A comparison of structural and immunological data further showed that antibody orientation on bound antigen and the capacity to form multivalent antigen-antibody complexes on target cells were key determinants of ADCC potency, with the latter process having the greater impact. These studies provide atomic-level definition of A32-like epitopes implicated as targets of protective antibodies in RV144. Moreover, these studies establish that epitope structure and mode of antibody binding can dramatically affect the potency of Fc-mediated effector function against HIV-1. These results provide key insights for understanding, refining, and improving the outcome of HIV vaccine trials, in which relevant immune responses are facilitated by A32-like elicited responses.
IMPORTANCE HIV-1 Env is a primary target for antibodies elicited during infection. Although a small number of infected individuals elicit broadly neutralizing antibodies, the bulk of the humoral response consists of antibodies that do not neutralize or do so with limited breadth but may effect protection through Fc receptor-dependent processes, such as antibody-dependent cellular cytotoxicity (ADCC). Understanding these nonneutralizing responses is an important aspect of elucidating the complete spectrum of immune response against HIV-1 infection. With this report, we provide the first atomic-level definition of nonneutralizing CD4-induced epitopes in the N-terminal region of the HIV-1 gp120 (A32-like epitopes). Further, our studies point to the dominant role of precise epitope targeting and mode of antibody attachment in ADCC responses even when largely overlapping epitopes are involved. Such information provides key insights into the mechanisms of Fc-mediated function of antibodies to HIV-1 and will help us understand the outcome of vaccine trials based on humoral immunity.
C1 [Acharya, Priyamvada; Huang, Chih-chin; Do Kwon, Young; Louder, Robert K.; Luongo, Timothy S.; McLellan, Jason S.; Pancera, Marie; Yang, Yongping; Zhang, Baoshan; Kwong, Peter D.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Tolbert, William D.; Gohain, Neelakshi; Wu, Xueji; Yu, Lei; Liu, Tongyun; Huang, Wensheng; Flinko, Robin; Foulke, James S., Jr.; Sajadi, Mohammad M.; Kamin-Lewis, Roberta; Guan, Yongjun; DeVico, Anthony L.; Lewis, George K.; Pazgier, Marzena] Univ Maryland, Sch Med, Inst Human Virol, Baltimore, MD 21201 USA.
[Tolbert, William D.; Gohain, Neelakshi; Wu, Xueji; Pazgier, Marzena] Univ Maryland, Sch Med, Dept Biochem & Mol Biol, Baltimore, MD 21201 USA.
[Yu, Lei; Liu, Tongyun; Huang, Wensheng; Flinko, Robin; Kamin-Lewis, Roberta; Guan, Yongjun; Lewis, George K.] Univ Maryland, Sch Med, Dept Microbiol & Immunol, Baltimore, MD 21201 USA.
[Foulke, James S., Jr.; Sajadi, Mohammad M.; DeVico, Anthony L.] Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA.
[Sajadi, Mohammad M.] VA Maryland Hlth Care Ctr, Med Care Clin Ctr, Baltimore, MD USA.
[Robinson, James E.] Tulane Univ, Med Ctr, Dept Pediat, New Orleans, LA 70118 USA.
[Martin, Loic] CEA, iBiTecS, Serv Ingn Mol Prot, Gif Sur Yvette, France.
RP Pazgier, M (reprint author), Univ Maryland, Sch Med, Inst Human Virol, Baltimore, MD 21201 USA.
EM mpazgier@ihv.umaryland.edu
RI Kwon, Young Do/A-6957-2010; Gohain, Neelakshi/P-7493-2015; MARTIN,
loic/E-1627-2011
OI MARTIN, loic/0000-0002-7940-2955
FU Intramural Research Program of the VRC, National Institute of Allergy
and Infectious Diseases, NIH from The Bill and Melinda Gates Foundation
[OPP1033109]; National Institute of Allergy and Infectious Diseases
(NIAID)/NIH [R01 AI-084830, R01 AI-087181, 5K23AI084580-04]; U.S.
Department of Energy, Basic Energy Sciences, Office of Science
[W-31-109-Eng-38]; U.S. Department of Energy Office of Biological and
Environmental Research; National Institutes of Health (NIH) National
Center for Research Resources, Biomedical Technology Program
[P41RR001209]; National Institute of General Medical Sciences
FX Support for this work was provided by the Intramural Research Program of
the VRC, National Institute of Allergy and Infectious Diseases, NIH, by
grant OPP1033109 from The Bill and Melinda Gates Foundation (to G.K.L.),
by National Institute of Allergy and Infectious Diseases (NIAID)/NIH
grants R01 AI-084830 and R01 AI-087181 (to G.K.L) and 5K23AI084580-04
(to M.M.S.). Use of sector 22 (Southeast Region Collaborative Access
team) at the Advanced Photon Source was supported by the U.S. Department
of Energy, Basic Energy Sciences, Office of Science, under contract
number W-31-109-Eng-38. Additionally, crystallographic data were
collected at the Stanford Synchrotron Radiation Lightsource (SSRL), a
Directorate of the SLAC National Accelerator Laboratory and an Office of
Science User Facility operated for the U.S. Department of Energy Office
of Science by Stanford University. The SSRL Structural Molecular Biology
Program is supported by the U.S. Department of Energy Office of
Biological and Environmental Research, by the National Institutes of
Health (NIH) National Center for Research Resources, Biomedical
Technology Program (P41RR001209), and by the National Institute of
General Medical Sciences.
NR 69
TC 34
Z9 34
U1 0
U2 12
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
EI 1098-5514
J9 J VIROL
JI J. Virol.
PD NOV
PY 2014
VL 88
IS 21
BP 12895
EP 12906
DI 10.1128/JVI.02194-14
PG 12
WC Virology
SC Virology
GA AR1BN
UT WOS:000343314900059
PM 25165110
ER
PT J
AU Ferenczy, MW
Major, EO
AF Ferenczy, Michael W.
Major, Eugene O.
TI Contamination of SVG p12 Cells with BK Polyomavirus Occurred after
Deposit in the American Type Culture Collection
SO JOURNAL OF VIROLOGY
LA English
DT Letter
ID HUMAN ASTROCYTES; LINE SVG; INFECTION; JC; SEQUENCES
C1 [Ferenczy, Michael W.; Major, Eugene O.] NINDS, Lab Mol Med & Neurosci, NIH, Bethesda, MD 20892 USA.
RP Ferenczy, MW (reprint author), NINDS, Lab Mol Med & Neurosci, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
EM michael.ferenczy@.nih.gov; majorg@ninds.nih.gov
FU Intramural NIH HHS
NR 9
TC 0
Z9 0
U1 0
U2 1
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
EI 1098-5514
J9 J VIROL
JI J. Virol.
PD NOV
PY 2014
VL 88
IS 21
BP 12928
EP 12929
DI 10.1128/JVI.01600-14
PG 2
WC Virology
SC Virology
GA AR1BN
UT WOS:000343314900064
PM 25288626
ER
PT J
AU Anema, A
Kluberg, S
Wilson, K
Hogg, RS
Khan, K
Hay, SI
Tatem, AJ
Brownstein, JS
AF Anema, Aranka
Kluberg, Sheryl
Wilson, Kumanan
Hogg, Robert S.
Khan, Kamran
Hay, Simon I.
Tatem, Andrew J.
Brownstein, John S.
TI Digital surveillance for enhanced detection and response to outbreaks
SO LANCET INFECTIOUS DISEASES
LA English
DT Editorial Material
ID INTERNATIONAL HEALTH REGULATIONS
C1 [Anema, Aranka; Kluberg, Sheryl; Brownstein, John S.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA.
[Anema, Aranka; Kluberg, Sheryl; Brownstein, John S.] Harvard Univ, MIT, Div Hlth Sci & Technol, Childrens Hosp,Informat Program, Boston, MA 02115 USA.
[Anema, Aranka] Univ British Columbia, Fac Land & Food Syst, Dept Food Nutr & Hlth, Div Int Nutr, Vancouver, BC V5Z 1M9, Canada.
[Wilson, Kumanan] Univ Ottawa, Ottawa Hosp Res Inst, Ottawa, ON, Canada.
[Hogg, Robert S.] Simon Fraser Univ, Fac Hlth Sci, Burnaby, BC V5A 1S6, Canada.
[Hogg, Robert S.] St Pauls Hosp, British Columbia Ctr Excellence HIV AIDS, Vancouver, BC V6Z 1Y6, Canada.
[Khan, Kamran] St Michaels Hosp, Li Ka Shing Knowledge Inst, Toronto, ON M5B 1W8, Canada.
[Hay, Simon I.] Univ Oxford, Dept Zool, Spatial Ecol & Epidemiol Grp, Oxford OX1 3PS, England.
[Hay, Simon I.; Tatem, Andrew J.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Tatem, Andrew J.] Univ Southampton, Dept Geog & Environm, Southampton, Hants, England.
[Tatem, Andrew J.] Flowminder Fdn, Stockholm, Sweden.
RP Anema, A (reprint author), Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA.
EM aranka.anema@childrens.harvard.edu
RI Hay, Simon/F-8967-2015;
OI Hay, Simon/0000-0002-0611-7272; Hogg, Robert/0000-0003-3463-5488
FU Canadian Institutes of Health Research; NIAID NIH HHS [U19 AI089674,
U19AI089674]; NLM NIH HHS [R01 LM010812, R01LM010812]; Wellcome Trust
[095066]
NR 9
TC 4
Z9 4
U1 0
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1473-3099
EI 1474-4457
J9 LANCET INFECT DIS
JI Lancet Infect. Dis.
PD NOV
PY 2014
VL 14
IS 11
BP 1035
EP 1037
PG 3
WC Infectious Diseases
SC Infectious Diseases
GA AR7EZ
UT WOS:000343743700010
PM 25444397
ER
PT J
AU Akula, N
Barb, J
Jiang, X
Wendland, JR
Choi, KH
Sen, SK
Hou, L
Chen, DTW
Laje, G
Johnson, K
Lipska, BK
Kleinman, JE
Corrada-Bravo, H
Detera-Wadleigh, S
Munson, PJ
McMahon, FJ
AF Akula, N.
Barb, J.
Jiang, X.
Wendland, J. R.
Choi, K. H.
Sen, S. K.
Hou, L.
Chen, D. T. W.
Laje, G.
Johnson, K.
Lipska, B. K.
Kleinman, J. E.
Corrada-Bravo, H.
Detera-Wadleigh, S.
Munson, P. J.
McMahon, F. J.
TI RNA-sequencing of the brain transcriptome implicates dysregulation of
neuroplasticity, circadian rhythms and GTPase binding in bipolar
disorder
SO MOLECULAR PSYCHIATRY
LA English
DT Article
DE gene expression; Gene Ontology; genome-wide association studies; long
noncoding RNAs; microarrays
ID MICROARRAY GENE-EXPRESSION; LONG NONCODING RNAS; GENOME-WIDE; PREFRONTAL
CORTEX; SCHIZOPHRENIA; ASSOCIATION; CELLS; SEQ; LINKAGE; NETWORK
AB RNA-sequencing (RNA-seq) is a powerful technique to investigate the complexity of gene expression in the human brain. We used RNA-seq to survey the brain transcriptome in high-quality postmortem dorsolateral prefrontal cortex from 11 individuals diagnosed with bipolar disorder (BD) and from 11 age-and gender-matched controls. Deep sequencing was performed, with over 350 million reads per specimen. At a false discovery rate of <5%, we detected five differentially expressed (DE) genes and 12 DE transcripts, most of which have not been previously implicated in BD. Among these, Prominin 1/CD133 and ATP-binding cassette-sub-family G-member2 (ABCG2) have important roles in neuroplasticity. We also show for the first time differential expression of long noncoding RNAs (lncRNAs) in BD. DE transcripts include those of serine/arginine-rich splicing factor 5 (SRSF5) and regulatory factor X4 (RFX4), which along with lncRNAs have a role in mammalian circadian rhythms. The DE genes were significantly enriched for several Gene Ontology categories. Of these, genes involved with GTPase binding were also enriched for BD-associated SNPs from previous genome-wide association studies, suggesting that differential expression of these genes is not simply a consequence of BD or its treatment. Many of these findings were replicated by microarray in an independent sample of 60 cases and controls. These results highlight common pathways for inherited and non-inherited influences on disease risk that may constitute good targets for novel therapies.
C1 [Akula, N.; Jiang, X.; Wendland, J. R.; Hou, L.; Chen, D. T. W.; Laje, G.; Detera-Wadleigh, S.; McMahon, F. J.] NIMH, Human Genet Branch, Intramural Res Program, NIH,US Dept HHS, Bethesda, MD 20892 USA.
[Barb, J.; Munson, P. J.] NIH, Math & Stat Comp Lab, Ctr Informat Technol, US Dept HHS, Bethesda, MD 20892 USA.
[Choi, K. H.] Uniformed Serv Univ Hlth Sci, Dept Psychiat, Bethesda, MD 20814 USA.
[Sen, S. K.] NHGRI, Genet Dis Res Branch, NIH, US Dept HHS, Bethesda, MD 20892 USA.
[Johnson, K.] NINDS, Bioinformat Sect, Informat Technol & Bioinformat Program, Div Intramural Res,NIH,US Dept HHS, Bethesda, MD 20892 USA.
[Lipska, B. K.] NIMH, Human Brain Collect Core, Div Intramural Res Programs, Hlth Intramural Res Program,NIH,UD Dept HHS, Bethesda, MD 20892 USA.
[Kleinman, J. E.] Lieber Inst Brain Dev, Baltimore, MD USA.
[Corrada-Bravo, H.] Univ Maryland, Inst Adv Comp Studies, Dept Comp Sci, College Pk, MD 20742 USA.
[Corrada-Bravo, H.] Univ Maryland, Ctr Bioinformat & Computat Biol, College Pk, MD 20742 USA.
RP Akula, N (reprint author), NIMH, Human Genet Branch, Intramural Res Program, NIH,US Dept HHS, Bethesda, MD 20892 USA.
EM akulan@mail.nih.gov
RI Hou, Liping/G-1648-2011; Lipska, Barbara/E-4569-2017;
OI Hou, Liping/0000-0003-3972-245X; McMahon, Francis/0000-0002-9469-305X;
Corrada Bravo, Hector/0000-0002-1255-4444
FU Intramural Research Program of the NIMH [ZIAMH002810, K99MH085098]
FX This study was supported by the Intramural Research Program of the NIMH
(grant no. ZIAMH002810 and K99MH085098). RNA from postmortem brain
tissue was donated by The Stanley Medical Research Institute's brain
collection courtesy of Drs Michael B Knable, E Fuller Torrey, Maree J
Webster, Serge Weis and Robert H Yolken. Data analysis was done on the
high-performance computational Biowulf cluster at NIH.
NR 55
TC 23
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U1 4
U2 18
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1359-4184
EI 1476-5578
J9 MOL PSYCHIATR
JI Mol. Psychiatr.
PD NOV
PY 2014
VL 19
IS 11
BP 1179
EP 1185
DI 10.1038/mp.2013.170
PG 7
WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry
SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry
GA AR5ZT
UT WOS:000343662300005
PM 24393808
ER
PT J
AU Xia, K
Guo, H
Hu, Z
Xun, G
Zuo, L
Peng, Y
Wang, K
He, Y
Xiong, Z
Sun, L
Pan, Q
Long, Z
Zou, X
Li, X
Li, W
Xu, X
Lu, L
Liu, Y
Hu, Y
Tian, D
Long, L
Ou, J
Liu, Y
Li, X
Zhang, L
Pan, Y
Chen, J
Peng, H
Liu, Q
Luo, X
Su, W
Wu, L
Liang, D
Dai, H
Yan, X
Feng, Y
Tang, B
Li, J
Miedzybrodzka, Z
Xia, J
Zhang, Z
Luo, X
Zhang, X
St Clair, D
Zhao, J
Zhang, F
AF Xia, K.
Guo, H.
Hu, Z.
Xun, G.
Zuo, L.
Peng, Y.
Wang, K.
He, Y.
Xiong, Z.
Sun, L.
Pan, Q.
Long, Z.
Zou, X.
Li, X.
Li, W.
Xu, X.
Lu, L.
Liu, Y.
Hu, Y.
Tian, D.
Long, L.
Ou, J.
Liu, Y.
Li, X.
Zhang, L.
Pan, Y.
Chen, J.
Peng, H.
Liu, Q.
Luo, X.
Su, W.
Wu, L.
Liang, D.
Dai, H.
Yan, X.
Feng, Y.
Tang, B.
Li, J.
Miedzybrodzka, Z.
Xia, J.
Zhang, Z.
Luo, X.
Zhang, X.
St Clair, D.
Zhao, J.
Zhang, F.
TI Common genetic variants on 1p13.2 associate with risk of autism
SO MOLECULAR PSYCHIATRY
LA English
DT Article
DE association fine mapping; autism; common genetic variants; genome-wide
association study; human genetics
ID DE-NOVO MUTATIONS; LINKED MENTAL-RETARDATION; COPY NUMBER VARIATION;
GENOME-WIDE LINKAGE; SPECTRUM DISORDERS; UBIQUITIN; REVEALS; SCAN;
ENCODES; COMPLEX
AB Autism is a highly heritable neurodevelopmental disorder, and known genetic variants, mostly rare, account only for a small proportion of cases. Here we report a genome-wide association study on autism using two Chinese cohorts as gene discovery (n = 2150) and three data sets of European ancestry populations for replication analysis of top association signals. Meta-analysis identified three single-nucleotide polymorphisms, rs936938 (P = 4.49 x 10(-8) ), non-synonymous rs6537835 (P = 3.26 x 10(-8)) and rs1877455 (P = 8.70 x 10(-8)), and related haplotypes, AMPD1-NRAS-CSDE1, TRIM33 and TRIM33-BCAS2, associated with autism; all were mapped to a previously reported linkage region (1p13.2) with autism. These genetic associations were further supported by a cis-acting regulatory effect on the gene expressions of CSDE1, NRAS and TRIM33 and by differential expression of CSDE1 and TRIM33 in the human prefrontal cortex of post-mortem brains between subjects with and those without autism. Our study suggests TRIM33 and NRAS-CSDE1 as candidate genes for autism, and may provide a novel insight into the etiology of autism.
C1 [Xia, K.; Guo, H.; Hu, Z.; Peng, Y.; Xiong, Z.; Pan, Q.; Long, Z.; Li, X.; Li, W.; Xu, X.; Lu, L.; Liu, Y.; Hu, Y.; Tian, D.; Long, L.; Zhang, L.; Pan, Y.; Chen, J.; Peng, H.; Liu, Q.; Su, W.; Wu, L.; Liang, D.; Dai, H.; Yan, X.; Feng, Y.; Tang, B.; Li, J.; Xia, J.; Zhang, Z.; Zhao, J.] Cent S Univ, State Key Lab Med Genet, Changsha 410078, Hunan, Peoples R China.
[Xia, K.; Guo, H.; Hu, Z.; Peng, Y.; Xiong, Z.] Cent S Univ, Sch Biol Sci & Technol, Changsha 410078, Hunan, Peoples R China.
[Guo, H.; St Clair, D.; Zhang, F.] NIMH, Div Intramural Res Programs, NIH, Bethesda, MD 20892 USA.
[Xun, G.; He, Y.; Ou, J.; Liu, Y.; Li, X.; Luo, X.; Zhao, J.] Cent S Univ, Xiangya Hosp 2, Mental Hlth Inst, Changsha 410078, Hunan, Peoples R China.
[Zuo, L.; Luo, X.] Yale Univ, Dept Psychiat, New Haven, CT 06520 USA.
[Wang, K.; Zhang, X.] State Key Lab Incubation Base Dermatol, Hefei, Anhui, Peoples R China.
[Zou, X.] Sun Yat Sen Univ, Hosp 3, Dept Pediat, Guangzhou, Guangdong, Peoples R China.
[Yan, X.; Feng, Y.; Tang, B.] Cent S Univ, Xiangya Hosp, Changsha 410078, Hunan, Peoples R China.
[Miedzybrodzka, Z.; St Clair, D.] Univ Aberdeen, Royal Cornhill Hosp, Aberdeen, Scotland.
[Zhang, F.] Johns Hopkins Univ, Lieber Inst Brain Dev, Baltimore, MD USA.
RP Xia, K (reprint author), Cent S Univ, State Key Lab Med Genet, 110 Xiangya Rd, Changsha 410078, Hunan, Peoples R China.
EM xiakun48@163.com; zhaojingpingcsu@163.com; fzhang20@jhmi.edu
FU Autism Genetic Resources Exchange (AGRE); Simons Foundation for Autism
Research Initiative (SFARI); National Basic Research Program of China
[2012CB517900, 2011CB510002]; National Natural Science Foundation of
China [81330027, 81161120544]; National Alliance for Research on
Schizophrenia and Depression (NARSAD) [17616]; National Institute of
Mental Health, The National Institutes of Health in the United States
FX We are grateful to all the children with autism, their families and to
the normal controls who participated in this study. We thank Autism
Speaks for sharing resources from the Autism Genetic Resources Exchange
(AGRE), the Simons Foundation for Autism Research Initiative (SFARI) for
providing data from the Simons Simplex Collection (SCC), the NIH GWAS
Data Repository (AGP data set: phs000267.v1.p1) and the Contributing
Investigator(s) who contributed the phenotype and genotype data from
his/her original studies. We also thank Mr Tianzhang Ye, Dr Carlo
Colantuoni and Dr Joel E Kleinman for assisting in accessing the brain
expression data and Dr Elizabeth Sherman for comments. The research was
supported by the National Basic Research Program of China (2012CB517900,
2011CB510002), the National Natural Science Foundation of China
(81330027, 81161120544), the National Alliance for Research on
Schizophrenia and Depression (NARSAD) Award (17616 to LZ) and Intramural
Research Program funding from the National Institute of Mental Health,
The National Institutes of Health in the United States.
NR 37
TC 20
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U1 7
U2 26
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1359-4184
EI 1476-5578
J9 MOL PSYCHIATR
JI Mol. Psychiatr.
PD NOV
PY 2014
VL 19
IS 11
BP 1212
EP 1219
DI 10.1038/mp.2013.146
PG 8
WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry
SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry
GA AR5ZT
UT WOS:000343662300010
PM 24189344
ER
PT J
AU Conejero-Goldberg, C
Gomar, JJ
Bobes-Bascaran, T
Hyde, TM
Kleinman, JE
Herman, MM
Chen, S
Davies, P
Goldberg, TE
AF Conejero-Goldberg, C.
Gomar, J. J.
Bobes-Bascaran, T.
Hyde, T. M.
Kleinman, J. E.
Herman, M. M.
Chen, S.
Davies, P.
Goldberg, T. E.
TI APOE2 enhances neuroprotection against Alzheimer's disease through
multiple molecular mechanisms
SO MOLECULAR PSYCHIATRY
LA English
DT Article
DE Alzheimer's disease; APOE2; biomarkers; gene expression; human brain;
neuroprotection
ID APOLIPOPROTEIN-E GENOTYPE; ARGYROPHILIC GRAIN DISEASE; AMYLOID-BETA
PEPTIDE; E EPSILON-2 ALLELE; TRANSGENIC MICE; E GENE;
EXTRACELLULAR-MATRIX; BRAIN; ASSOCIATION; BIOMARKERS
AB The common APOE2 gene variant is neuroprotective against Alzheimer's disease (AD) and reduces risk by nearly 50%. However, the mechanisms by which APOE2 confers neuroprotection are largely unknown. Here we showed that ApoE protein abundance in human postmortem cortex follows an isoform-dependent pattern (E2>E3>E4). We also identified a unique downstream transcriptional profile determined by microarray and characterized by downregulation of long-term potentiation (LTP) related transcripts and upregulation of extracellular matrix (ECM)/integrin-related transcripts in E2 cases and corroborated this finding at the protein level by demonstrating increases in ECM collagens and laminins. In vivo studies of healthy older individuals demonstrated a unique and advantageous biomarker signature in E2 carriers. APOE2 also reduced the risk of mild cognitive impairment to AD conversion by half. Our findings suggest that ApoE2 protein abundance, coupled with its inability to bind to LDLRs, may act to increase amyloid-beta (Ab) clearance. In addition, increased ECM and reduced LTP-related expression results in diminished activity-dependent Ab secretion and/or excitotoxicity, and thus also promotes neuroprotection.
C1 [Conejero-Goldberg, C.; Gomar, J. J.; Bobes-Bascaran, T.; Chen, S.; Davies, P.; Goldberg, T. E.] Litwin Zucker Ctr Study Alzheimers Dis, Hofstra North Shore LIJ Sch Med, Feinstein Inst, Manhasset, NY 11030 USA.
[Gomar, J. J.] FIDMAG, Hermanas Hosp, St Boi de Llobregat, Spain.
[Hyde, T. M.; Kleinman, J. E.] Lieber Inst Brain Dev, Neuropathol Sect, Baltimore, MD USA.
[Herman, M. M.] NIMH, Sect Neuropathol, Clin Brain Disorders Branch, GCAPP,IRP,NIH, Bethesda, MD 20892 USA.
RP Goldberg, TE (reprint author), Litwin Zucker Ctr Study Alzheimers Dis, Hofstra North Shore LIJ Sch Med, Feinstein Inst, Manhasset, NY 11030 USA.
EM tgoldber@nshs.edu
RI Bobes-Bascaran, Maria/F-2208-2015;
OI Gomar, Jesus/0000-0002-6995-4270
FU Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes
of Health) [U01 AG024904]; National Institute on Aging; National
Institute of Biomedical Imaging and Bioengineering; NIH [P30 AG010129,
K01 AG030514]; Dana Foundation; Litwin Zucker Alzheimer's Disease
Center; GCAPP; IRP; NIMH
FX Funding for this study was provided by the Litwin Zucker Alzheimer's
Disease Center (CCG, TEG, JJG, TBB, SC, PD) and GCAPP, IRP, NIMH (TMH,
JEK, MH). Data collection and sharing for this project was funded by the
Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes
of Health Grant U01 AG024904). ADNI is funded by the National Institute
on Aging, the National Institute of Biomedical Imaging and
Bioengineering, and through generous contributions from the following:
Abbott, AstraZeneca AB, Bayer Schering Pharma AG, Bristol-Myers Squibb,
Eisai Global Clinical Development, Elan Corporation, Genentech, GE
Healthcare, GlaxoSmithKline, Innogenetics, Johnson and Johnson, Eli
Lilly, Medpace, Merck, Novartis AG, Pfizer, F. Hoffman-La Roche,
Schering-Plough, Synarc, as well as non-profit partners like the
Alzheimer's Association and Alzheimer's Drug Discovery Foundation, with
participation from the US Food and Drug Administration. Private sector
contributions to ADNI are facilitated by the Foundation for the National
Institutes of Health (http://www.fnih.org). The grantee organization is
the Northern California Institute for Research and Education, and the
study is coordinated by the Alzheimer's Disease Cooperative Study at the
University of California, San Diego, CA, USA. ADNI data are disseminated
by the Laboratory for Neuro Imaging at the University of California, Los
Angeles, CA, USA. This research was also supported by NIH grants P30
AG010129, K01 AG030514, and the Dana Foundation. The ADNI investigators
contributed to the design of ADNI, diagnoses, and data collection of
biomarkers, but not to the analyses and writing of this report.
NR 55
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PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1359-4184
EI 1476-5578
J9 MOL PSYCHIATR
JI Mol. Psychiatr.
PD NOV
PY 2014
VL 19
IS 11
BP 1243
EP 1250
DI 10.1038/mp.2013.194
PG 8
WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry
SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry
GA AR5ZT
UT WOS:000343662300014
PM 24492349
ER
PT J
AU Wessendorf, P
Vijg, J
Nussenzweig, A
Digweed, M
AF Wessendorf, Petra
Vijg, Jan
Nussenzweig, Andre
Digweed, Martin
TI Deficiency of the DNA repair protein nibrin increases the basal but not
the radiation induced mutation frequency in vivo
SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS
LA English
DT Article
DE DNA damage; Mismatch repair; Haploinsufficiency
ID NIJMEGEN-BREAKAGE-SYNDROME; ELEVATED MUTANT FREQUENCIES; TRANSGENIC
MOUSE MODEL; CANCER-RISK; COMET ASSAY; NBS1; MICE; GENE; CELLS;
HETEROZYGOTES
AB Nibrin (NBN) is a member of a DNA repair complex together with MRE11 and RAD50. The complex is associated particularly with the repair of DNA double strand breaks and with the regulation of cell cycle check points. Hypomorphic mutation of components of the complex leads to human disorders characterised by radiosensitivity and increased tumour occurrence, particularly of the lymphatic system. We have examined here the relationship between DNA damage, mutation frequency and mutation spectrum in vitro and in vivo in mouse models carrying NBN mutations and a lacZ reporter plasmid. We find that NBN mutation leads to increased spontaneous DNA damage in fibroblasts in vitro and high basal mutation rates in lymphatic tissue of mice in vivo. The characteristic mutation spectrum is dominated by single base transitions rather than the deletions and complex rearrangements expected after abortive repair of DNA double strand breaks. We conclude that in the absence of wild type nibrin, the repair of spontaneous errors, presumably arising during DNA replication, makes a major contribution to the basal mutation rate. This applies also to cells heterozygous for an NBN null mutation. Mutation frequencies after irradiation in vivo were not increased in mice with nibrin mutations as might have been expected considering the radiosensitivity of NBS patient cells in vitro. Evidently apoptosis is efficient, even in the absence of wild type nibrin. (C) 2014 Elsevier B.V. All rights reserved.
C1 [Wessendorf, Petra; Digweed, Martin] Charite, Inst Med & Human Genet, D-13353 Berlin, Germany.
[Vijg, Jan] Albert Einstein Coll Med, Michael F Price Ctr, Bronx, NY 10461 USA.
[Nussenzweig, Andre] NCI, Lab Genome Integr, NIH, Bethesda, MD 20892 USA.
RP Digweed, M (reprint author), Charite, Inst Med & Human Genet, Augustenburger Pl 1, D-13353 Berlin, Germany.
EM martin.digweed@charite.de
FU Deutsche Forschungsgemeinschaft [DI 505/3-1]; NIH
FX The authors are grateful to Bettina Ueberle, Klinik fuer Dermatologie
und Allergologie, Universitaetsklinikum Ulm, for instruction in the lacZ
assay and Brigitte Kottgen, Institut fur Klinische Chemie und
Pathochemie, Charite Berlin for instruction in the comet assay. We thank
Susanne Rothe for mouse genotyping, Vittoria von Petersdorff for
assistance in DNA sequencing and Moonsook Lee for assistance with the
lacZ assay. This work was supported by the Deutsche
Forschungsgemeinschaft (grant number DI 505/3-1 to M.D.) and NIH to J.V.
NR 38
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U1 0
U2 3
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0027-5107
EI 1873-135X
J9 MUTAT RES-FUND MOL M
JI Mutat. Res.-Fundam. Mol. Mech. Mutagen.
PD NOV
PY 2014
VL 769
BP 11
EP 16
DI 10.1016/j.mrfmmm.2014.07.001
PG 6
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology
GA AR5LH
UT WOS:000343625700002
PM 25771721
ER
PT J
AU Zhu, JF
Shevach, EM
AF Zhu, Jinfang
Shevach, Ethan M.
TI TCR signaling fuels T-reg cell suppressor function
SO NATURE IMMUNOLOGY
LA English
DT Editorial Material
ID AUTOIMMUNITY; RESPONSES
C1 [Zhu, Jinfang; Shevach, Ethan M.] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA.
RP Zhu, JF (reprint author), NIAID, Immunol Lab, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM jfzhu@niaid.nih.gov; eshevach@niaid.nih.gov
RI Zhu, Jinfang/B-7574-2012
FU Intramural NIH HHS [ZIA AI001169-03, ZIA AI000959-04, ZIA AI000959-08]
NR 11
TC 4
Z9 4
U1 1
U2 10
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 NOV
PY 2014
VL 15
IS 11
BP 1002
EP 1003
PG 2
WC Immunology
SC Immunology
GA AR5RH
UT WOS:000343640700003
PM 25329180
ER
PT J
AU Johnson, DH
Via, LE
Kim, P
Laddy, D
Lau, CY
Weinstein, EA
Jain, S
AF Johnson, Daniel H.
Via, Laura E.
Kim, Peter
Laddy, Dominick
Lau, Chuen-Yen
Weinstein, Edward A.
Jain, Sanjay
TI Nuclear imaging: A powerful novel approach for tuberculosis
SO NUCLEAR MEDICINE AND BIOLOGY
LA English
DT Article
DE Drug-resistance; PET; SPECT; Probe-design; Pharmacokinetics
ID POSITRON-EMISSION-TOMOGRAPHY; METASTATIC BREAST-CANCER; XPERT MTB/RIF
ASSAY; MYCOBACTERIUM-TUBERCULOSIS; PULMONARY TUBERCULOSIS; FDG PET/CT;
THERAPEUTIC RESPONSE; LATENT TUBERCULOSIS; F-18-FDG PET/CT;
BACTERIAL-INFECTIONS
AB Nearly 20 years after the World Health Organization declared tuberculosis (TB) a global public health emergency, TB still remains a major global threat with 8.6 million new cases and 1.3 million deaths annually. Mycobacterium tuberculosis adapts to a quiescent physiological state, and is notable for complex interaction with the host, producing poorly-understood disease states ranging from latent infection to fully active disease. Of the approximately 2.5 billion people latently infected with M. tuberculosis, many will develop reactivation disease (relapse), years after the initial infection. While progress has been made on some fronts, the alarming spread of multidrug-resistant, extensively drug-resistant, and more recently totally-drug resistant strains is of grave concern. New tools are urgently needed for rapidly diagnosing TB, monitoring TB treatments and to allow unique insights into disease pathogenesis. Nuclear bioimaging is a powerful, noninvasive tool that can rapidly provide three-dimensional views of disease processes deep within the body and conduct noninvasive longitudinal assessments of the same patient. In this review, we discuss the application of nuclear bioimaging to TB, including the current state of the field, considerations for radioprobe development, study of TB drug pharmacokinetics in infected tissues, and areas of research and clinical needs that could be addressed by nuclear bioimaging. These technologies are an emerging field of research, overcome several fundamental limitations of current tools, and will have a broad impact on both basic research and patient care. Beyond diagnosis and monitoring disease, these technologies will also allow unique insights into understanding disease pathogenesis: and expedite bench-to-bedside translation of new therapeutics. Finally, since molecular imaging is readily available for humans, validated tracers will become valuable tools for clinical applications. Published by Elsevier Inc.
C1 [Johnson, Daniel H.; Via, Laura E.; Kim, Peter; Lau, Chuen-Yen] NIAID, NIH, Bethesda, MD 20892 USA.
[Laddy, Dominick] Aeras, Rockville, MD USA.
[Weinstein, Edward A.] FDA CDER, Silver Spring, MD USA.
[Jain, Sanjay] Johns Hopkins Univ, Sch Med, Ctr TB Res, Ctr Infect & Inflammat Imaging Res, Baltimore, MD USA.
[Jain, Sanjay] Johns Hopkins Univ, Sch Med, Dept Pediat, Baltimore, MD 21205 USA.
RP Johnson, DH (reprint author), NIAID, DAIDS, NIH, 5601 Fisher Lane,Rm 9E39 MSC 9830, Rockville, MD 20852 USA.
EM daniel.johnson@nih.gov
OI Via, Laura/0000-0001-6074-9521
FU NIH [DP2-OD006492, R01-HL116316]; AIDS Clinical Trials Group
Administrative Novel Formulations Supplement; NIH, NIAID
FX This study was funded by the NIH Director's New Innovator Award
DP2-OD006492 (S.K.J.), R01-HL116316 (S.K.J.), and AIDS Clinical Trials
Group Administrative Novel Formulations Supplement (S.K.J.). We thank
Dr. William Eckelman (Molecular Tracer LLC) for comments. The authors do
not have a commercial or other association that might pose a conflict of
interest. The views expressed in review are those of the authors and do
not necessarily reflect the official policy or position of the U.S. Food
and Drug Administration, the Department of Health and Human Services, or
the United States Government, and should not be used for advertising or
product endorsement purposes. Reference to any specific commercial
products, process, or service by trade name, trademark, manufacturer, or
otherwise, does not constitute or imply its approval, endorsement,
recommendation, or favoring by the United States Government or any
department, agency, office, or branch thereof. Funding for this work was
provided (in part) by the Intramural Research Program of the NIH, NIAID.
NR 108
TC 7
Z9 7
U1 2
U2 27
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0969-8051
EI 1872-9614
J9 NUCL MED BIOL
JI Nucl. Med. Biol.
PD NOV-DEC
PY 2014
VL 41
IS 10
BP 777
EP 784
DI 10.1016/j.nucmedbio.2014.08.005
PG 8
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA AR5HE
UT WOS:000343614800001
PM 25195017
ER
PT J
AU Leggio, L
Zywiak, WH
Fricchione, SR
Edwards, SM
de la Monte, SM
Swift, RM
Kenna, GA
AF Leggio, Lorenzo
Zywiak, William H.
Fricchione, Samuel R.
Edwards, Steven M.
de la Monte, Suzanne M.
Swift, Robert M.
Kenna, George A.
TI Intravenous Ghrelin Administration Increases Alcohol Craving in
Alcohol-Dependent Heavy Drinkers: A Preliminary Investigation
SO BIOLOGICAL PSYCHIATRY
LA English
DT Article
DE Alcoholism; craving; cue-reactivity; feeding peptides; ghrelin;
neuroendocrinology
ID HORMONE SECRETAGOGUE RECEPTOR; CONDITIONED PLACE PREFERENCE; RAT ARCUATE
NUCLEUS; CONTAINING NEURONS; MESSENGER-RNA; FOOD-INTAKE; PLASMA;
PHARMACOKINETICS; REACTIVITY; DOPAMINE
AB Background: There is a need to identify novel pharmacologic targets to treat alcoholism. Animal and human studies suggest a role for ghrelin in the neurobiology of alcohol dependence and craving. Here, we were the first to test the hypothesis that intravenous administration of exogenous ghrelin acutely increases alcohol craving.
Methods: This was a double-blind, placebo-controlled human laboratory proof-of-concept study. Nontreatment-seeking, alcohol-dependent, heavy-drinking individuals were randomized to receive intravenous ghrelin 1 mcg/kg, 3 mcg/kg or 0 mcg/kg (placebo), followed by a cue-reactivity procedure, during which participants were exposed to neutral (juice) and alcohol cues. The primary outcome variable was the increase in alcohol craving (also called urge) for alcohol, assessed by the Alcohol Visual Analogue Scale.
Results: Out of 103 screenings, 45 individuals received the study drug. Repeated measures of analysis of covariance revealed a group effect across ghrelin doses in increasing alcohol craving (p < .05). A dose-specific examination revealed a significant effect of ghrelin 3 mcg/kg versus placebo in increasing alcohol craving (p < .05) with a large effect size (d = .94). By contrast, no significant ghrelin effect was found in increasing either urge to drink juice or food craving (p = ns). No significant differences in side effects were found (p = ns).
Conclusions: Intravenous administration of exogenous ghrelin increased alcohol craving in alcohol-dependent heavy-drinking individuals. Although the small sample requires confirmatory studies, these findings provide preliminary evidence that ghrelin may play a role in the neurobiology of alcohol craving, thus demonstrating a novel pharmacologic target for treatment.
C1 [Leggio, Lorenzo] NIAAA, Lab Clin & Translat Studies, Sect Clin Psychoneuroendocrinol & Neuropsychophar, Bethesda, MD 20892 USA.
NIDA, Intramural Res Program, NIH, Bethesda, MD 20892 USA.
[Leggio, Lorenzo; Fricchione, Samuel R.] Brown Univ, Ctr Alcohol & Addict Studies, Dept Behav & Social Sci, Providence, RI 02912 USA.
[Zywiak, William H.] Pacific Inst Res & Evaluat, Decis Sci Inst, Pawtucket, RI USA.
[Zywiak, William H.; Swift, Robert M.; Kenna, George A.] Brown Univ, Ctr Alcohol & Addict Studies, Dept Psychiat & Human Behav, Providence, RI 02912 USA.
[Edwards, Steven M.] Univ Nebraska, Dept Psychol, Lincoln, NE USA.
[de la Monte, Suzanne M.] Brown Univ, Rhode Isl Hosp, Dept Pathol, Dept Neurol & Neurosurg, Providence, RI 02912 USA.
[de la Monte, Suzanne M.] Brown Univ, Warren Alpert Med Sch, Providence, RI 02912 USA.
[Swift, Robert M.] Vet Affairs Med Ctr, Providence, RI USA.
RP Leggio, L (reprint author), NIAAA, 10 Ctr Dr 10CRC-15330,MSC 1108,Room 1-5429, Bethesda, MD 20892 USA.
EM lorenzo.leggio@nih.gov
RI Leggio, Lorenzo/M-2972-2016
FU National Institute on Alcohol Abuse and Alcoholism [R21-AA019709];
Division of Intramural Clinical and Biological Research of the National
Institute on Alcohol Abuse and Alcoholism; Intramural Research Program
of the National Institute on Drug Abuse
FX This study was funded by the National Institute on Alcohol Abuse and
Alcoholism, Grant R21-AA019709, awarded to Dr. Leggio while he was at
Brown University. Dr. Leggio's current work is supported by the Division
of Intramural Clinical and Biological Research of the National Institute
on Alcohol Abuse and Alcoholism and the Intramural Research Program of
the National Institute on Drug Abuse.
NR 54
TC 18
Z9 18
U1 1
U2 9
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 1
PY 2014
VL 76
IS 9
BP 734
EP 741
DI 10.1016/j.biopsych.2014.03.019
PG 8
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA AQ8QO
UT WOS:000343094800010
PM 24775991
ER
PT J
AU Yang, L
Karin, M
AF Yang, L.
Karin, M.
TI Roles of tumor suppressors in regulating tumor-associated inflammation
SO CELL DEATH AND DIFFERENTIATION
LA English
DT Review
ID NF-KAPPA-B; PANCREATIC DUCTAL ADENOCARCINOMA; CANCER-RELATED
INFLAMMATION; COLITIS-ASSOCIATED CANCER; SQUAMOUS-CELL CARCINOMA;
TGF-BETA; BREAST-CANCER; PROSTATE-CANCER; GENE-EXPRESSION; MYELOID CELLS
AB Loss or silencing of tumor suppressors (TSs) promotes neoplastic transformation and malignant progression. To date, most work on TS has focused on their cell autonomous effects. Recent evidence, however, demonstrates an important noncell autonomous role for TS in the control of tumor-associated inflammation. We review evidence from clinical data sets and mouse model studies demonstrating enhanced inflammation and altered tumor microenvironment (TME) upon TS inactivation. We discuss clinical correlations between tumor-associated inflammation and inactivation of TS, and their therapeutic implications. This review sets forth the concept that TS can also suppress tumor-associated inflammation, a concept that provides new insights into tumor-host interactions. We also propose that in some cases the loss of TS function in cancer can be overcome through inhibition of the resulting inflammatory response, regardless whether it is a direct or an indirect consequence of TS loss.
C1 [Yang, L.] NCI, Lab Canc Biol & Genet, NIH, Bethesda, MD 20892 USA.
[Karin, M.] Univ Calif San Diego, Sch Med, Dept Pharmacol & Pathol, Lab Gene Regulat & Signal Transduct, La Jolla, CA 92093 USA.
RP Yang, L (reprint author), NCI, Lab Canc Biol & Genet, NIH, 37 Convent Dr, Bethesda, MD 20892 USA.
EM yangl3@mail.nih.gov; karinoffice@ucsd.edu
NR 109
TC 9
Z9 9
U1 1
U2 17
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1350-9047
EI 1476-5403
J9 CELL DEATH DIFFER
JI Cell Death Differ.
PD NOV
PY 2014
VL 21
IS 11
BP 1677
EP 1686
DI 10.1038/cdd.2014.131
PG 10
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA AR0XE
UT WOS:000343296800003
PM 25190145
ER
PT J
AU Murakami, Y
Tian, L
Voss, OH
Margulies, DH
Krzewski, K
Coligan, JE
AF Murakami, Y.
Tian, L.
Voss, O. H.
Margulies, D. H.
Krzewski, K.
Coligan, J. E.
TI CD300b regulates the phagocytosis of apoptotic cells via
phosphatidylserine recognition
SO CELL DEATH AND DIFFERENTIATION
LA English
DT Article
ID IMMUNOGLOBULIN-LIKE RECEPTORS; CORPSE CLEARANCE; MACROPHAGES; MOUSE;
ENGULFMENT; IDENTIFICATION; RESPONSES; TIM-4; IMMUNORECEPTOR;
REQUIREMENT
AB The CD300 receptor family members are a group of molecules that modulate a variety of immune cell processes. We show that mouse CD300b (CLM7/LMIR5), expressed on myeloid cells, recognizes outer membrane-exposed phosphatidylserine (PS) and does not, as previously reported, directly recognize TIM1 or TIM4. CD300b accumulates in phagocytic cups along with F-actin at apoptotic cell contacts, thereby facilitating their engulfment. The CD300b-mediated activation signal is conveyed through CD300b association with the adaptor molecule DAP12, and requires a functional DAP12 ITAM motif. Binding of apoptotic cells promotes the activation of the PI3K-Akt kinase pathway in macrophages, while silencing of CD300b expression diminishes PI3K-Akt kinase activation and impairs efferocytosis. Collectively, our data show that CD300b recognizes PS as a ligand, and regulates the phagocytosis of apoptotic cells via the DAP12 signaling pathway.
C1 [Murakami, Y.; Tian, L.; Voss, O. H.; Krzewski, K.; Coligan, J. E.] NIAID, Receptor Cell Biol Sect, Immunogenet Lab, NIH, Rockville, MD USA.
[Margulies, D. H.] NIAID, Mol Biol Sect, Immunol Lab, Bethesda, MD 20892 USA.
RP Coligan, JE (reprint author), 12441 Parklawn Dr,Twinbrook 2,Room 205, Rockville, MD 20852 USA.
EM jcoligan@niaid.nih.gov
OI Margulies, David/0000-0001-8530-7375
FU intramural programs of the National Institute of Allergy and Infectious
Diseases
FX We thank Dr. John P. Cannon for the CD300b-Fc and NITR-Fc vectors. We
thank Dr. Shigekazu Nagata for the pMX-puro TIM1 and TIM4 vectors, and
Dr. Joseph Brzostowski for the technical help with the microscopy. We
thank Ms. Lisa Boyd for SPR technical assistance, and Dr. Patrick H.
Brown for DLS. We thank Dr. Aleksandra Gil-Krzewska, and Venkateswara
Simhadri for their critical comments. This study was supported by the
intramural programs of the National Institute of Allergy and Infectious
Diseases.
NR 50
TC 13
Z9 13
U1 1
U2 9
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1350-9047
EI 1476-5403
J9 CELL DEATH DIFFER
JI Cell Death Differ.
PD NOV
PY 2014
VL 21
IS 11
BP 1746
EP 1757
DI 10.1038/cdd.2014.86
PG 12
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA AR0XE
UT WOS:000343296800009
PM 25034781
ER
PT J
AU Mammen, AL
AF Mammen, Andrew L.
TI Necrotizing myopathies: beyond statins
SO CURRENT OPINION IN RHEUMATOLOGY
LA English
DT Review
DE anti-HMG-CoA reductase; autoimmune; muscle; myopathy; myositis;
necrotizing; signal recognition particle; statin
ID SIGNAL-RECOGNITION PARTICLE; T-CELLS; DERMATOMYOSITIS; POLYMYOSITIS;
ANTIBODIES; AUTOANTIBODIES; ANTI-3-HYDROXY-3-METHYLGLUTARYL-COENZYME
AB Purpose of review
This review discusses the spectrum of diseases associated with a necrotizing muscle biopsy. Although patients with toxic myopathies, endocrine dysfunction, and heritable myopathies may have prominent necrosis on muscle biopsy, immune-mediated myopathies are emphasized here.
Recent findings
A decade ago, immune-mediated necrotizing myopathy was recognized as a distinct form of myositis. Recent evidence now suggests that immune-mediated necrotizing myopathy is not one disease, but can be divided on the basis of the presence of distinct autoantibodies recognizing either the signal recognition particle or 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase. Anti-HMG-CoA reductase-positive patients can be further subdivided into those with and without statin exposure, the latter of which may be particularly refractory to immunosuppressive therapy.
Summary
A significant number of patients with autoimmune myopathy have a predominantly necrotizing muscle biopsy with minimal lymphocytic infiltration. This biopsy finding occurs in various forms myositis, including the antisynthetase syndrome, scleroderma-associated myopathy, antisignal recognition particle-associated myopathy, statin-associated anti-HMG-CoA reductase-positive autoimmune myopathy, and statin-naive anti-HMG-CoA reductase-positive myopathy. Future progress in elucidating pathogenic mechanisms and defining optimal treatment strategies may depend upon recognizing these distinct forms of myositis and analyzing them as separate entities.
C1 NIAMSD, Muscle Dis Unit, Lab Muscle Stem Cells & Gene Express, NIH, Bethesda, MD 20892 USA.
RP Mammen, AL (reprint author), NIAMSD, Muscle Dis Unit, Lab Muscle Stem Cells & Gene Express, NIH, 50 South Dr,Room 1146,Bldg 50,MSC 8024, Bethesda, MD 20892 USA.
EM andrew.mammen@nih.gov
NR 25
TC 6
Z9 7
U1 0
U2 7
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1040-8711
EI 1531-6963
J9 CURR OPIN RHEUMATOL
JI Curr. Opin. Rheumatol.
PD NOV
PY 2014
VL 26
IS 6
BP 679
EP 683
DI 10.1097/BOR.0000000000000106
PG 5
WC Rheumatology
SC Rheumatology
GA AQ7KQ
UT WOS:000342994000012
PM 25203117
ER
PT J
AU Schiffenbauer, A
AF Schiffenbauer, Adam
TI Imaging: seeing muscle in new ways
SO CURRENT OPINION IN RHEUMATOLOGY
LA English
DT Review
DE idiopathic inflammatory myopathies; magnetic resonance spectroscopy;
MRI; PET; ultrasound
ID MAGNETIC-RESONANCE-SPECTROSCOPY; POSITRON-EMISSION-TOMOGRAPHY;
INCLUSION-BODY MYOSITIS; MUSCULAR INFLAMMATION; HEALTHY-VOLUNTEERS;
SKELETAL-MUSCLE; MRI; DERMATOMYOSITIS; INFORMATION; PET/CT
AB Purpose of review
The idiopathic inflammatory myopathies are diseases that can be difficult to diagnose and evaluate, but diagnosis has been improved by modern imaging techniques. Advances in imaging continue to be made. Therefore, it is necessary to evaluate the implications of these advances for the diagnosis, understanding, and management of muscle diseases.
Recent findings
There have been advances in imaging across multiple modalities. Several new radiotracers show an improved ability to focus on inflammation better than older agents. Magnetic resonance spectroscopy has shown the ability to diagnose several idiopathic inflammatory myopathy mimics. MRI reveals previously unknown areas of disease when used for full-body imaging. Ultrasound has the ability to differentiate inclusion body myositis from other myopathies.
Summary
Currently, MRI and ultrasound offer the most information about these diseases in a given patient, and new advances in these fields have served to only make them more useful. New advances in nuclear imaging and magnetic resonance spectroscopy are showing that they have utility as well, and advances in these techniques may allow them to come to the forefront in evaluating difficult idiopathic inflammatory myopathy patients.
C1 [Schiffenbauer, Adam] NIEHS, Environm Autoimmun Grp, Intramural Res Program, NIH, Bethesda, MD USA.
RP Schiffenbauer, A (reprint author), 10 Ctr Dr,Bldg 10 Room 6C432D, Bethesda, MD 20892 USA.
EM schiffenbauera2@mail.nih.gov
OI Schiffenbauer, Adam/0000-0001-9964-9966
FU NIH, National Institute of Environmental Health Sciences
FX This research was supported by the Intramural Research Program of the
NIH, National Institute of Environmental Health Sciences.
NR 28
TC 1
Z9 2
U1 2
U2 6
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1040-8711
EI 1531-6963
J9 CURR OPIN RHEUMATOL
JI Curr. Opin. Rheumatol.
PD NOV
PY 2014
VL 26
IS 6
BP 712
EP 716
DI 10.1097/BOR.0000000000000105
PG 5
WC Rheumatology
SC Rheumatology
GA AQ7KQ
UT WOS:000342994000017
PM 25215416
ER
PT J
AU Burbelo, PD
O'Hanlon, TP
AF Burbelo, Peter D.
O'Hanlon, Terrance P.
TI New autoantibody detection technologies yield novel insights into
autoimmune disease
SO CURRENT OPINION IN RHEUMATOLOGY
LA English
DT Review
DE antigen arrays; autoantibodies; autoimmunity; fluid-phase immunoassays;
immunoassay; luciferase immunoprecipitation systems; pathogenic
autoantibodies; phage display
ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; CYTOSOLIC 5'-NUCLEOTIDASE 1A;
INCLUSION-BODY MYOSITIS; RHEUMATOID-ARTHRITIS; MICROARRAY ANALYSIS;
MULTIPLE-SCLEROSIS; GAMMA AUTOANTIBODY; HUMAN PEPTIDOME; PROTEIN ARRAYS;
ANTI-LA
AB Purpose of review
The purpose of this review is to highlight recent progress in autoantibody detection technologies and describe how these methods are providing novel information and insights into autoimmune disorders.
Recent findings
In recent years, alternative methods such as comprehensive phage display, fluid-phase immunoassays, and antigen microarrays have been developed for autoantigen discovery and profiling autoantibody responses. Compared with classic approaches such as Western blot and ELISA, these methods show improved diagnostic performance, the ability to measure antibody responses to multiple targets, and/or allow more quantitative analyses. Specific notable findings include uncovering previously unrecognized autoantigens, the improved classification of patient clinical phenotypes, and the discovery of pathogenic autoantibodies promoting disease.
Summary
Advances in immunoassay technologies offer many opportunities for understanding the relationship between autoantibody detection and the myriad complex, clinical phenotypes characteristic of most autoimmune diseases. Further simplification and standardization of these technologies may allow routine integration into clinical practice with improved diagnostic and therapeutic outcomes.
C1 [Burbelo, Peter D.] Natl Inst Dent & Craniofacial Res, Dent Clin Res Core, NIH, Bethesda, MD 20892 USA.
[O'Hanlon, Terrance P.] NIEHS, Environm Autoimmun Grp, NIH, Bethesda, MD USA.
RP Burbelo, PD (reprint author), Natl Inst Dent & Craniofacial Res, Dent Clin Res Core, NIH, 10 Ctr Dr,Bldg 10,Rm 5N102, Bethesda, MD 20892 USA.
EM burbelop@nidcr.nih.gov
FU NIH, Division of Intramural Research; National Institute of Dental and
Craniofacial Research; National Institute of Environmental Health
Sciences
FX The research was supported by the Intramural Research Program of the
NIH, Division of Intramural Research, National Institute of Dental and
Craniofacial Research and National Institute of Environmental Health
Sciences.
NR 43
TC 4
Z9 4
U1 3
U2 24
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1040-8711
EI 1531-6963
J9 CURR OPIN RHEUMATOL
JI Curr. Opin. Rheumatol.
PD NOV
PY 2014
VL 26
IS 6
BP 717
EP 723
DI 10.1097/BOR.0000000000000107
PG 7
WC Rheumatology
SC Rheumatology
GA AQ7KQ
UT WOS:000342994000018
PM 25203116
ER
PT J
AU Rider, LG
Danko, K
Miller, FW
AF Rider, Lisa G.
Danko, Katalin
Miller, Frederick W.
TI Myositis registries and biorepositories: powerful tools to advance
clinical, epidemiologic and pathogenic research
SO CURRENT OPINION IN RHEUMATOLOGY
LA English
DT Review
DE biorepository; dermatomyositis; idiopathic inflammatory myopathies;
inclusion body myositis; juvenile dermatomyositis; myositis
autoantibody; natural history; phenotype; polymyositis; registry
ID IDIOPATHIC INFLAMMATORY MYOPATHIES; INCLUSION-BODY MYOSITIS; JUVENILE
DERMATOMYOSITIS PATIENTS; TERM-FOLLOW-UP; ANTIBODY-POSITIVE
DERMATOMYOSITIS; SYSTEMIC AUTOIMMUNE-DISEASES; MONOZYGOTIC TWINS
SUGGEST; INTERSTITIAL LUNG-DISEASE; CUTANEOUS ASSESSMENT-TOOL; MUSCLE
BIOPSY SAMPLES
AB Purpose of review
Clinical registries and biorepositories have proven extremely useful in many studies of diseases, especially rare diseases. Given their rarity and diversity, the idiopathic inflammatory myopathies, or myositis syndromes, have benefited from individual researchers' collections of cohorts of patients. Major efforts are being made to establish large registries and biorepositories that will allow many additional studies to be performed that were not possible before. Here, we describe the registries developed by investigators and patient support groups that are currently available for collaborative research purposes.
Recent findings
We have identified 46 myositis research registries, including many with biorepositories, which have been developed for a wide variety of purposes and have resulted in great advances in understanding the range of phenotypes, clinical presentations, risk factors, pathogenic mechanisms, outcome assessment, therapeutic responses, and prognoses. These are now available for collaborative use to undertake additional studies. Two myositis patient registries have been developed for research, and myositis patient support groups maintain demographic registries with large numbers of patients available to be contacted for potential research participation.
Summary
Investigator-initiated myositis research registries and biorepositories have proven extremely useful in understanding many aspects of these rare and diverse autoimmune diseases. These registries and biorepositories, in addition to those developed by myositis patient support groups, deserve continued support to maintain the momentum in this field as they offer major opportunities to improve understanding of the pathogenesis and treatment of these diseases in cost-effective ways.
C1 [Rider, Lisa G.; Miller, Frederick W.] Natl Inst Environm Sci, Environm Autoimmun Grp, Program Clin Res, NIH,DHHS, Bethesda, MD 20892 USA.
[Danko, Katalin] Univ Debrecen, Dept Internal Med 3, Med & Hlth Sci Ctr, Div Immunol, H-4012 Debrecen, Hungary.
RP Rider, LG (reprint author), Natl Inst Environm Sci, Environm Autoimmun Grp, NIH, DHHS, Clin Res Ctr Room 4-2352,10 Ctr Dr,MSC 1301, Bethesda, MD 20892 USA.
EM riderl@mail.nih.gov
OI Rider, Lisa/0000-0002-6912-2458; Miller, Frederick/0000-0003-2831-9593
FU NIH, National Institute of Environmental Health Sciences [ES101074,
ES101081]
FX This work was supported in part by the Intramural Research Programs of
NIH, National Institute of Environmental Health Sciences (project number
ES101074 and ES101081).
NR 165
TC 3
Z9 3
U1 0
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1040-8711
EI 1531-6963
J9 CURR OPIN RHEUMATOL
JI Curr. Opin. Rheumatol.
PD NOV
PY 2014
VL 26
IS 6
BP 724
EP 741
DI 10.1097/BOR.0000000000000119
PG 18
WC Rheumatology
SC Rheumatology
GA AQ7KQ
UT WOS:000342994000019
PM 25225838
ER
PT J
AU Davies, JOJ
Stringaris, K
Barrett, AJ
Rezvani, K
AF Davies, James O. J.
Stringaris, Kate
Barrett, A. John
Rezvani, Katayoun
TI Opportunities and limitations of natural killer cells as adoptive
therapy for malignant disease
SO CYTOTHERAPY
LA English
DT Review
DE C-type lectin; graft-versus-leukemia; immunotherapy; killer
immunoglobulin-like receptors; natural cytotoxiciv receptors; natural
killer
ID IMMUNOGLOBULIN-LIKE RECEPTOR; CHRONIC MYELOID-LEUKEMIA; MHC CLASS-I; HLA
CLASS-I; KIR LIGAND INCOMPATIBILITY; UNRELATED DONOR TRANSPLANTATION;
BONE-MARROW-TRANSPLANTATION; HUMAN T-LYMPHOCYTES; NK CELLS;
MULTIPLE-MYELOMA
AB Although natural killer (NK) cells can be readily generated for adoptive therapy with current techniques, their optimal application to treat malignant diseases requires an appreciation of the dynamic balance between signals that either synergize with or antagonize each other. Individuals display wide differences in NK function that determine their therapeutic efficacy. The ability of NK cells to kill target cells or produce cytokines depends on the balance between signals from activating and inhibitory cell-surface receptors. The selection of NK cells with a predominant activating profile is critical for delivering successful anti-tumor activity. This can be achieved through selection of killer immunoglobulin-like receptor mismatched NK donors and by use of blocking molecules against inhibitory pathways. Optimum NK cytotoxicity may require licensing or priming with tumor cells. Recent discoveries in the molecular and cellular biology of NK cells inform in the design of new strategies, including adjuvant therapies, to maximize the cytotoxic potential of NK cells for adoptive transfer to treat human malignancies.
C1 [Davies, James O. J.; Stringaris, Kate] Univ London Imperial Coll Sci Technol & Med, Dept Haematol, London, England.
[Barrett, A. John] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA.
[Rezvani, Katayoun] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
RP Rezvani, K (reprint author), Dept Stem Cell Transplantat & Cellular Therapy, 1515 Holcombe Blvd,Box 448, Houston, TX 77030 USA.
EM KRezvani@mdanderson.org
OI Davies, James/0000-0002-4108-4357
FU MD Anderson Cancer Center Leukemia SPORE Grant [CA100632]; Leuka
registered charity [286231]
FX This research was supported in part by the MD Anderson Cancer Center
Leukemia SPORE Grant CA100632, Leuka registered charity (286231).
NR 136
TC 12
Z9 14
U1 2
U2 11
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1465-3249
EI 1477-2566
J9 CYTOTHERAPY
JI Cytotherapy
PD NOV
PY 2014
VL 16
IS 11
BP 1453
EP 1466
DI 10.1016/j.jcyt.2014.03.009
PG 14
WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell
Biology; Hematology; Medicine, Research & Experimental
SC Cell Biology; Biotechnology & Applied Microbiology; Hematology; Research
& Experimental Medicine
GA AR1PC
UT WOS:000343356100002
PM 24856895
ER
PT J
AU Cheng, YZ
Brunner, AL
Kremer, S
DeVido, SK
Stefaniuk, CM
Kassis, JA
AF Cheng, Yuzhong
Brunner, Alayne L.
Kremer, Stefanie
DeVido, Sarah K.
Stefaniuk, Catherine M.
Kassis, Judith A.
TI Co-regulation of invected and engrailed by a complex array of regulatory
sequences in Drosophila
SO DEVELOPMENTAL BIOLOGY
LA English
DT Article
DE Enhancers; Gene expression; Gene regulation; Segmentation
ID ENHANCER-PROMOTER COMMUNICATION; RESPONSE ELEMENTS; GENE-EXPRESSION;
CELL FATE; MELANOGASTER; PATTERN; ULTRABITHORAX; TRANSCRIPTION;
COMPARTMENT; REPRESSION
AB invected (inv) and engrailed (en) form a gene complex that extends about 115 kb. These two genes encode highly related homeodomain proteins that are co-regulated in a complex manner throughout development. Our dissection of inv/en regulatory DNA shows that most enhancers are spread throughout a 62 kb region. We used two types of constructs to analyze the function of this DNA: P-element based reporter constructs with small pieces of DNA fused to the en promoter driving lacZ expression and large constructs with HA-tagged en and inv inserted in the genome with the phiC31 system. In addition, we generated deletions of inv and en DNA in situ and assayed their effects on inv/en expression. Our results support and extend our knowledge of inv/en regulation. First, inv and en share regulatory DNA, most of which is flanking the en transcription unit. In support of this, a 79-kb HA-en transgene can rescue inv en double mutants to viable, fertile adults. In contrast, an 84-kb HA-inv transgene lacks most of the enhancers for inv/en expression. Second, there are multiple enhancers for inv/en stripes in embryos; some of these may be redundant but others play discrete roles at different stages of embryonic development. Finally, no small reporter construct gave expression in the posterior compartment of imaginal discs, a hallmark of inv/en expression. Robust expression of HA-en in the posterior compartment of imaginal discs is evident from the 79-kb HA-en transgene, while a 45-kb HA-en transgene gives weaker, variable imaginal disc expression. We suggest that the activity of the imaginal disc enhancer (s) is dependent on the chromatin structure of the inv/en domain. Published by Elsevier Inc.
C1 [Cheng, Yuzhong; Brunner, Alayne L.; Kremer, Stefanie; DeVido, Sarah K.; Stefaniuk, Catherine M.; Kassis, Judith A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Genom Differentiat, NIH, Bethesda, MD 20892 USA.
RP Kassis, JA (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Genom Differentiat, NIH, Bethesda, MD 20892 USA.
EM jkassis@mail.nih.gov
OI Kassis, Judith/0000-0001-9268-3213
FU Intramural Research Program of the Eunice Kennedy Shriver National
Institute of Child Health and Human Development, National Institutes of
Health
FX We thank Tom Kornberg for en lambda phage, en and inv mutant flies, and
encouragement; Pat O'Farrell for en lambda phage and anti-En antibody;
the Harvard Exelixis and Bloomington stock centers for fly stocks; and
Miki Fujioka, Jim Jaynes, and Payal Ray and two helpful reviewers for
comments on this manuscript. This work was supported by the Intramural
Research Program of the Eunice Kennedy Shriver National Institute of
Child Health and Human Development, National Institutes of Health.
NR 42
TC 3
Z9 4
U1 0
U2 11
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 1
PY 2014
VL 395
IS 1
BP 131
EP 143
DI 10.1016/j.ydbio.2014.08.021
PG 13
WC Developmental Biology
SC Developmental Biology
GA AQ9SC
UT WOS:000343195000013
PM 25172431
ER
PT J
AU Seyerle, AA
Young, AM
Jeff, JM
Melton, PE
Jorgensen, NW
Lin, Y
Carty, CL
Deelman, E
Heckbert, SR
Hindorff, LA
Jackson, RD
Martin, LW
Okin, PM
Perez, MV
Psaty, BM
Soliman, EZ
Whitsel, EA
North, KE
Laston, S
Kooperberg, C
Avery, CL
AF Seyerle, Amanda A.
Young, Alicia M.
Jeff, Janina M.
Melton, Phillip E.
Jorgensen, Neal W.
Lin, Yi
Carty, Cara L.
Deelman, Ewa
Heckbert, Susan R.
Hindorff, Lucia A.
Jackson, Rebecca D.
Martin, Lisa W.
Okin, Peter M.
Perez, Marco V.
Psaty, Bruce M.
Soliman, Elsayed Z.
Whitsel, Eric A.
North, Kari E.
Laston, Sandra
Kooperberg, Charles
Avery, Christy L.
TI Evidence of Heterogeneity by Race/Ethnicity in Genetic Determinants of
QT Interval
SO EPIDEMIOLOGY
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; CARDIOVASCULAR-DISEASE; EPIDEMIOLOGY PAGE;
AMERICAN-INDIANS; COMMON VARIANTS; CANDIDATE GENE; DE-POINTES; RISK;
DURATION; METAANALYSIS
AB Background: QT interval (QT) prolongation is an established risk factor for ventricular tachyarrhythmia and sudden cardiac death. Previous genome-wide association studies in populations of the European descent have identified multiple genetic loci that influence QT, but few have examined these loci in ethnically diverse populations.
Methods: Here, we examine the direction, magnitude, and precision of effect sizes for 21 previously reported SNPs from 12 QT loci, in populations of European (n = 16,398), African (n = 5,437), American Indian (n = 5,032), Hispanic (n = 1,143), and Asian (n = 932) descent as part of the Population Architecture using Genomics and Epidemiology (PAGE) study. Estimates obtained from linear regression models stratified by race/ethnicity were combined using inverse-variance weighted meta-analysis. Heterogeneity was evaluated using Cochran's Q test.
Results: Of 21 SNPs, 7 showed consistent direction of effect across all 5 populations, and an additional 9 had estimated effects that were consistent across 4 populations. Despite consistent direction of effect, 9 of 16 SNPs had evidence (P < 0.05) of heterogeneity by race/ethnicity. For these 9 SNPs, linkage disequilibrium plots often indicated substantial variation in linkage disequilibrium patterns among the various racial/ethnic groups, as well as possible allelic heterogeneity.
Conclusions: These results emphasize the importance of analyzing racial/ethnic groups separately in genetic studies. Furthermore, they underscore the possible utility of trans-ethnic studies to pinpoint underlying casual variants influencing heritable traits such as QT.
C1 [Seyerle, Amanda A.; Whitsel, Eric A.; North, Kari E.; Avery, Christy L.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27514 USA.
[Young, Alicia M.; Lin, Yi; Carty, Cara L.; Kooperberg, Charles] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA.
[Jeff, Janina M.] Mt Sinai Sch Med, Charles Bronfman Inst Personalized Med, New York, NY USA.
[Melton, Phillip E.] Univ Western Australia, Ctr Genet Origins Hlth & Dis, Crawley, Australia.
[Jorgensen, Neal W.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
[Deelman, Ewa] Univ So Calif, Inst Informat Sci, Marina Del Rey, CA 90292 USA.
[Deelman, Ewa] Univ So Calif, Dept Comp Sci, Marina Del Rey, CA USA.
[Heckbert, Susan R.; Psaty, Bruce M.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
[Heckbert, Susan R.; Psaty, Bruce M.] Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA.
[Heckbert, Susan R.; Psaty, Bruce M.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA USA.
[Hindorff, Lucia A.] NHGRI, Off Populat Genom, NIH, Bethesda, MD 20892 USA.
[Jackson, Rebecca D.] Ohio State Med Ctr, Dept Internal Med, Columbus, OH USA.
[Martin, Lisa W.] George Washington Univ, Div Cardiol, Washington, DC USA.
[Okin, Peter M.] Weill Cornell Med Coll, Dept Med, New York, NY USA.
[Perez, Marco V.] Stanford Univ, Div Cardiovasc Med, Stanford, CA 94305 USA.
[Psaty, Bruce M.] Univ Washington, Div Med, Seattle, WA 98195 USA.
[Psaty, Bruce M.] Univ Washington, Div Hlth Serv, Seattle, WA 98195 USA.
[Soliman, Elsayed Z.] Wake Forest Sch Med, Epidemiol Cardiol Res Ctr EPICARE, Winston Salem, NC USA.
[Whitsel, Eric A.] Univ N Carolina, Dept Med, Chapel Hill, NC 27514 USA.
[Laston, Sandra] Texas Biomed Res Inst, Dept Genet, San Antonio, TX USA.
RP Seyerle, AA (reprint author), Univ N Carolina, Dept Epidemiol, CVS Plaza,137 E Franklin St,Suite 306, Chapel Hill, NC 27514 USA.
EM aseyerle@email.unc.edu
OI Melton, Phillip/0000-0003-4026-2964; Martin, Lisa
Warsinger/0000-0003-4352-0914; Seyerle, Amanda/0000-0001-5660-3837
FU Population Architecture Using Genomics and Epidemiology (PAGE) program -
National Human Genome Research Institute (NHGRI); CALiCo [U01HG004803];
EAGLE [U01HG004798]; MEC [U01HG004802]; WHI [U01HG004790]; Coordinating
Center [U01HG004801]
FX This work was supported by the Population Architecture Using Genomics
and Epidemiology (PAGE) program, which is funded by the National Human
Genome Research Institute (NHGRI), supported by U01HG004803 (CALiCo),
U01HG004798 (EAGLE), U01HG004802 (MEC), U01HG004790 (WHI), and
U01HG004801 (Coordinating Center), and their respective NHGRI ARA
supplements. The contents of this paper are solely the responsibility of
the authors and do not necessarily represent the official views of the
NIH. The complete list of PAGE members can be found at
http://www.pagestudy.org.
NR 40
TC 6
Z9 6
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1044-3983
EI 1531-5487
J9 EPIDEMIOLOGY
JI Epidemiology
PD NOV
PY 2014
VL 25
IS 6
BP 790
EP 798
DI 10.1097/EDE.0000000000000168
PG 9
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA AQ8XJ
UT WOS:000343122000002
PM 25166880
ER
PT J
AU Menvielle, G
Truong, T
Jellouli, F
Stucker, I
Brenner, H
Field, JK
Hosgood, HD
Lan, Q
Landi, MT
Hung, RJ
Lazarus, P
McLaughlin, J
Morgenstern, H
Muscat, JE
Ruano-Ravina, A
Schwartz, AG
Seow, A
Spitz, MR
Tardon, A
Zhang, ZF
Luce, D
AF Menvielle, Gwenn
Truong, Therese
Jellouli, Fatima
Stuecker, Isabelle
Brenner, Hermann
Field, John K.
Hosgood, H. Dean
Lan, Qing
Landi, Maria Teresa
Hung, Rayjean J.
Lazarus, Philip
McLaughlin, John
Morgenstern, Hal
Muscat, Joshua E.
Ruano-Ravina, Alberto
Schwartz, Ann G.
Seow, Adeline
Spitz, Margaret R.
Tardon, Adonina
Zhang, Zuo-Feng
Luce, Daniele
TI Education and Lung Cancer Among Never Smokers
SO EPIDEMIOLOGY
LA English
DT Letter
ID ENVIRONMENTAL TOBACCO-SMOKE; RISK; INEQUALITIES
C1 [Menvielle, Gwenn] Pierre Louis Inst Epidemiol & Publ Hlth, INSERM, UMR S 1136, Paris, France.
[Truong, Therese; Jellouli, Fatima; Stuecker, Isabelle] Ctr Epidemiol & Populat Hlth, INSERM, U1018, Villejuif, France.
[Brenner, Hermann] German Canc Res Ctr, Div Clin Epidemiol & Aging Res, Heidelberg, Germany.
[Field, John K.] Univ Liverpool, Canc Res Ctr, Inst Translat Med, Liverpool L69 3BX, Merseyside, England.
[Hosgood, H. Dean; Lan, Qing; Landi, Maria Teresa] NCI, Div Canc Epidemiol & Genet, Rockville, MD USA.
[Hung, Rayjean J.] Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, Toronto, ON M5G 1X5, Canada.
[Lazarus, Philip] Washington State Univ, Coll Pharm, Dept Pharmaceut Sci, Spokane, WA USA.
[McLaughlin, John] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada.
[Morgenstern, Hal] Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA.
[Muscat, Joshua E.] Penn State Coll Med, Dept Publ Hlth Sci, Hershey, PA USA.
[Ruano-Ravina, Alberto] Univ Santiago de Compostela, Dept Prevent Med & Publ Hlth, Santiago De Compostela, Spain.
[Schwartz, Ann G.] Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA.
[Seow, Adeline] Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore 117548, Singapore.
[Spitz, Margaret R.] Dan L Duncan Canc Ctr, Houston, TX USA.
[Tardon, Adonina] Univ Oviedo, Dept Med, Oviedo, Asturias, Spain.
[Zhang, Zuo-Feng] Univ Calif Los Angeles, Fielding Sch Publ Hlth, Dept Epidemiol, Los Angeles, CA USA.
[Luce, Daniele] Irset, INSERM, U1085, Pointe A Pitre 97110, Guadeloupe.
RP Menvielle, G (reprint author), Pierre Louis Inst Epidemiol & Publ Hlth, INSERM, UMR S 1136, Paris, France.
EM gwenn.menvielle@inserm.fr
RI Hung, Rayjean/A-7439-2013; LUCE, Daniele/J-9125-2015; Brenner,
Hermann/B-4627-2017; Menvielle, Gwenn/E-7201-2017;
OI Brenner, Hermann/0000-0002-6129-1572; Field, John/0000-0003-3951-6365;
Luce, Daniele/0000-0002-1708-4584
FU NCI NIH HHS [P30CA022453, N01PC35145, P01 CA068384, P01 CA6838, P30
CA022453, R01 CA060691, R01 CA127219, R01CA060691, R01CA127219]; NIDA
NIH HHS [R01 DA026815]
NR 8
TC 2
Z9 2
U1 1
U2 10
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1044-3983
EI 1531-5487
J9 EPIDEMIOLOGY
JI Epidemiology
PD NOV
PY 2014
VL 25
IS 6
BP 934
EP 935
DI 10.1097/EDE.0000000000000183
PG 2
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA AQ8XJ
UT WOS:000343122000028
PM 25265142
ER
PT J
AU Muller, YL
Thearle, MS
Piaggi, P
Hanson, RL
Hoffman, D
Gene, B
Mahkee, D
Huang, K
Kobes, S
Votruba, S
Knowler, WC
Bogardus, C
Baier, LJ
AF Muller, Yunhua L.
Thearle, Marie S.
Piaggi, Paolo
Hanson, Robert L.
Hoffman, Duncan
Gene, Brittany
Mahkee, Darin
Huang, Ke
Kobes, Sayuko
Votruba, Susanne
Knowler, William C.
Bogardus, Clifton
Baier, Leslie J.
TI Common genetic variation in and near the melanocortin 4 receptor gene
(MC4R) is associated with body mass index in American Indian adults and
children
SO HUMAN GENETICS
LA English
DT Article
ID PIMA-INDIANS; ENERGY-EXPENDITURE; DIABETES-MELLITUS; CARBOHYDRATE
OXIDATION; RESPIRATORY CHAMBER; EATING BEHAVIOR; METABOLIC-RATE; FAT
MASS; OBESITY; MUTATIONS
AB Six rare functional coding mutations were previously identified in melanocortin 4 receptor (MC4R) in 6,760 American Indians. Individuals heterozygous for one of these mutations become obese while young. We now investigate whether common non-coding variation near MC4R also contributes to obesity. Fifty-six tag single-nucleotide polymorphisms (SNPs) were genotyped in 3,229 full-heritage Pima Indians, and nine of these SNPs which showed evidence for association were genotyped in additional 3,852 mixed-heritage American Indians. Associations of SNPs with maximum body mass index (BMI) in adulthood (n = 5,918), BMI z score in childhood (n = 5,350), percent body fat (n = 864), energy expenditure (n = 358) and ad libitum food intake (n = 178) were assessed. Conditional analyses demonstrated that SNPs, rs74861148 and rs483125, were independently associated with BMI in adulthood (beta = 0.68 kg/m(2) per risk allele, p = 5 x 10(-5); beta = 0.58 kg/m2, p = 0.002, respectively) and BMI z score in childhood (beta = 0.05, p = 0.02; beta = 0.07, p = 0.01, respectively). One haplotype (frequency = 0.35) of the G allele at rs74861148 and the A allele at rs483125 provided the strongest evidence for association with adult BMI (beta = 0.89 kg/m(2), p = 5.5 x 10(-7)), and was also associated with childhood BMI z score (beta = 0.08, p = 0.001). In addition, a promoter SNP rs11872992 was nominally associated with adult BMI (beta = 0.61 kg/m(2), p = 0.05) and childhood BMI z score (beta = 0.11, p = 0.01), where the risk allele also modestly decreased transcription in vitro by 12 % (p = 0.005). This risk allele was further associated with increased percent body fat (beta = 2.2 %, p = 0.002), increased food intake (beta = 676 kcal/day, p = 0.007) and decreased energy expenditure (beta = -53.4 kcal/day, p = 0.054). Common and rare variation in MC4R contributes to obesity in American Indians.
C1 [Muller, Yunhua L.; Thearle, Marie S.; Piaggi, Paolo; Hanson, Robert L.; Hoffman, Duncan; Gene, Brittany; Mahkee, Darin; Huang, Ke; Kobes, Sayuko; Votruba, Susanne; Knowler, William C.; Bogardus, Clifton; Baier, Leslie J.] NIDDK, Phoenix Epidemiol & Clin Res Branch, NIH, Phoenix, AZ 85004 USA.
RP Baier, LJ (reprint author), NIDDK, Phoenix Epidemiol & Clin Res Branch, NIH, 445 North 5th St, Phoenix, AZ 85004 USA.
EM ymuller@mail.nih.gov; lbaier@phx.niddk.nih.gov
RI Hanson, Robert/O-3238-2015;
OI Hanson, Robert/0000-0002-4252-7068; Piaggi, Paolo/0000-0003-2774-9161
FU intramural research program of the National Institute of Diabetes and
Digestive and Kidney Diseases, National Institutes of Health
FX We thank the clinical staff of the Phoenix Epidemiology and Clinical
Research Branch for conducting the study. We also thank all the
participants from the Gila River Indian Community. This work was
supported by the intramural research program of the National Institute
of Diabetes and Digestive and Kidney Diseases, National Institutes of
Health.
NR 37
TC 7
Z9 8
U1 0
U2 9
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 NOV
PY 2014
VL 133
IS 11
BP 1431
EP 1441
DI 10.1007/s00439-014-1477-6
PG 11
WC Genetics & Heredity
SC Genetics & Heredity
GA AR0UU
UT WOS:000343287900009
PM 25103139
ER
PT J
AU Stewart, DR
Messinger, Y
Williams, GM
Yang, JD
Field, A
Schultz, KAP
Harney, LA
Doros, LA
Dehner, LP
Hill, DA
AF Stewart, Douglas R.
Messinger, Yoav
Williams, Gretchen M.
Yang, Jiandong
Field, Amanda
Schultz, Kris Ann P.
Harney, Laura A.
Doros, Leslie A.
Dehner, Louis P.
Hill, D. Ashley
TI Nasal chondromesenchymal hamartomas arise secondary to germline and
somatic mutations of DICER1 in the pleuropulmonary blastoma tumor
predisposition disorder
SO HUMAN GENETICS
LA English
DT Article
ID REGISTRY; CHILDREN
AB Nasal chondromesenchymal hamartoma (NCMH) is a rare nasal tumor that typically presents in young children. We previously reported on NCMH occurrence in children with pleuropulmonary blastoma (PPB), a rare pulmonary dysembryonic sarcoma that is the hallmark neoplasm in the PPBassociated DICER1 tumor predisposition disorder. Original pathologic materials from individuals with a PPB, PPB-associated tumor and/or a DICER1 mutation were centrally reviewed by the International PPB Registry. Paraffin-embedded NCMH tumor tissue was available in three cases. Laser-capture microdissection was used to isolate mesenchymal spindle cells and cartilage in one case for Sanger sequencing of DICER1. Nine patients (5F/4M) had PPB and NCMH. NCMH was diagnosed at a median age of 10 years (range 6-21 years). NCMH developed 4.5-13 years after PPB. Presenting NCMH symptoms included chronic sinusitis and nasal congestion. Five patients had bilateral tumors. Local NCMH recurrences required several surgical resections in two patients, but all nine patients were alive at 0-16 years of follow-up. Pathogenic germline DICER1 mutations were found in 6/8 NCMH patients tested. In 2 of the patients with germline DICER1 mutations, somatic DICER1 missense mutations were also identified in their NCMH (E1813D; n = 2). Three additional PPB patients developed other nasal lesions seen in the general population (a Schneiderian papilloma, chronic sinusitis with cysts, and allergic nasal polyps with eosinophils). Two of these patients had germline DICER1 mutations. Pathogenic germline and somatic mutations of DICER1 in NCMH establishes that the genetic etiology of NCMH is similar to PPB, despite the disparate biological potential of these neoplasms.
C1 [Stewart, Douglas R.] NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD USA.
[Messinger, Yoav; Williams, Gretchen M.; Schultz, Kris Ann P.] Childrens Hosp & Clin Minnesota, Int Pleuropulm Blastoma Registry, Minneapolis, MN USA.
[Yang, Jiandong; Field, Amanda; Hill, D. Ashley] George Washington Univ, Childrens Natl Med Ctr, Dept Integrat Syst Biol, Div Pathol,Ctr Genet Med Res,Sch Med, Washington, DC USA.
[Harney, Laura A.] Westat Corp, Rockville, MD USA.
[Doros, Leslie A.] Childrens Natl Med Ctr, Div Oncol, Washington, DC 20010 USA.
[Dehner, Louis P.] Washington Univ, Med Ctr, Dept Pathol & Immunol, St Louis, MO USA.
RP Stewart, DR (reprint author), 9609 Med Ctr Dr Rm 6E450, Bethesda, MD 20892 USA.
EM drstewart@mail.nih.gov
FU Division of Cancer Epidemiology and Genetics (DCEG) of the National
Cancer Institute's Intramural Research Program; Intramural Research
Program of the NIH; National Cancer Institute; National Cancer Institute
[R01CA143167]
FX This work was supported by the Division of Cancer Epidemiology and
Genetics (DCEG) of the National Cancer Institute's Intramural Research
Program. This research was supported by the Intramural Research Program
of the NIH and the National Cancer Institute. D.A.H. is supported by
National Cancer Institute R01CA143167.
NR 32
TC 13
Z9 13
U1 0
U2 0
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 NOV
PY 2014
VL 133
IS 11
BP 1443
EP 1450
DI 10.1007/s00439-014-1474-9
PG 8
WC Genetics & Heredity
SC Genetics & Heredity
GA AR0UU
UT WOS:000343287900010
PM 25118636
ER
PT J
AU Zhu, PP
Denton, KR
Pierson, TM
Li, XJ
Blackstone, C
AF Zhu, Peng-Peng
Denton, Kyle R.
Pierson, Tyler Mark
Li, Xue-Jun
Blackstone, Craig
TI Pharmacologic rescue of axon growth defects in a human iPSC model of
hereditary spastic paraplegia SPG3A
SO HUMAN MOLECULAR GENETICS
LA English
DT Article
ID TUBULAR ER NETWORK; ENDOPLASMIC-RETICULUM; AUTOSOMAL-DOMINANT; TRANSPORT
DEFECTS; MEMBRANE-PROTEINS; ATLASTIN GTPASES; STRUCTURAL BASIS; CELL
MODEL; DISEASE; MUTATIONS
AB Hereditary spastic paraplegias are a large, diverse group of neurological disorders (SPG1-71) with the unifying feature of prominent lower extremity spasticity, owing to a length-dependent axonopathy of corticospinal motor neurons. The most common early-onset form of pure, autosomal dominant hereditary spastic paraplegia is caused by mutation in the ATL1 gene encoding the atlastin-1 GTPase, which mediates homotypic fusion of ER tubules to form the polygonal ER network. We have identified a p.Pro342Ser mutation in a young girl with pure SPG3A. This residue is in a critical hinge region of atlastin-1 between its GTPase and assembly domains, and it is conserved in all known eukaryotic atlastin orthologs. We produced induced pluripotent stem cells from skin fibroblasts and differentiated these into forebrain neurons to generate a human neuronal model for SPG3A. Axons of these SPG3A neurons showed impaired growth, recapitulating axonal defects in atlastin-1-depleted rat cortical neurons and impaired root hair growth in loss-of-function mutants of the ATL1 ortholog rhd3 in the plant Arabidopsis. Both the microtubule cytoskeleton and tubular ER are important for mitochondrial distribution and function within cells, and SPG3A neurons showed alterations in mitochondrial motility. Even so, it is not clear whether this change is involved in disease pathogenesis. The SPG3A axon growth defects could be rescued with microtubule-binding agents, emphasizing the importance of tubular ER interactions with the microtubule cytoskeleton in hereditary spastic paraplegia pathogenesis. The prominent alterations in axon growth in SPG3A neurons may represent a particularly attractive target for suppression in screens for novel pharmacologic agents.
C1 [Zhu, Peng-Peng; Blackstone, Craig] NINDS, Neurogenet Branch, NIH, Bethesda, MD 20892 USA.
[Denton, Kyle R.; Li, Xue-Jun] Univ Connecticut, Ctr Hlth, Dept Neurosci, Farmington, CT 06030 USA.
[Li, Xue-Jun] Univ Connecticut, Ctr Hlth, Stem Cell Inst, Farmington, CT 06030 USA.
[Pierson, Tyler Mark] Cedars Sinai Med Ctr, Dept Pediat, Los Angeles, CA 90048 USA.
[Pierson, Tyler Mark] Cedars Sinai Med Ctr, Dept Neurol, Los Angeles, CA 90048 USA.
[Pierson, Tyler Mark] Cedars Sinai Med Ctr, Regenerat Med Inst, Los Angeles, CA 90048 USA.
RP Li, XJ (reprint author), Univ Connecticut, Ctr Hlth, Dept Neurosci, Room E4029,MC 3401,263 Farmington Ave, Farmington, CT 06030 USA.
EM xjli@uchc.edu
FU Intramural Research Program of the NINDS, National Institutes of Health;
Spastic Paraplegia Foundation; Connecticut Stem Cell Research Grant
[11SCB24]
FX This work was supported by the Intramural Research Program of the NINDS,
National Institutes of Health, the Spastic Paraplegia Foundation, and a
Connecticut Stem Cell Research Grant (11SCB24).
NR 57
TC 12
Z9 13
U1 0
U2 8
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0964-6906
EI 1460-2083
J9 HUM MOL GENET
JI Hum. Mol. Genet.
PD NOV 1
PY 2014
VL 23
IS 21
BP 5638
EP 5648
DI 10.1093/hmg/ddu280
PG 11
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA AQ9UX
UT WOS:000343203600005
PM 24908668
ER
PT J
AU Hasumi, Y
Baba, M
Hasumi, H
Huang, Y
Lang, M
Reindorf, R
Oh, HB
Sciarretta, S
Nagashima, K
Haines, DC
Schneider, MD
Adelstein, RS
Schmidt, LS
Sadoshima, J
Linehan, WM
AF Hasumi, Yukiko
Baba, Masaya
Hasumi, Hisashi
Huang, Ying
Lang, Martin
Reindorf, Rachel
Oh, Hyoung-bin
Sciarretta, Sebastiano
Nagashima, Kunio
Haines, Diana C.
Schneider, Michael D.
Adelstein, Robert S.
Schmidt, Laura S.
Sadoshima, Junichi
Linehan, W. Marston
TI Folliculin (Flcn) inactivation leads to murine cardiac hypertrophy
through mTORC1 deregulation
SO HUMAN MOLECULAR GENETICS
LA English
DT Article
ID ACTIVATED PROTEIN-KINASE; TRANSCRIPTIONAL COACTIVATOR PGC-1-ALPHA;
HOGG-DUBE-SYNDROME; TUMOR-SUPPRESSOR; HEART-FAILURE; TRANSGENIC MICE;
IN-VIVO; MITOCHONDRIAL BIOGENESIS; MYOCARDIAL-CONTRACTILITY; DILATED
CARDIOMYOPATHY
AB Cardiac hypertrophy, an adaptive process that responds to increased wall stress, is characterized by the enlargement of cardiomyocytes and structural remodeling. It is stimulated by various growth signals, of which the mTORC1 pathway is a well-recognized source. Here, we show that loss of Flcn, a novel AMPK-mTOR interacting molecule, causes severe cardiac hypertrophy with deregulated energy homeostasis leading to dilated cardiomyopathy in mice. We found that mTORC1 activity was upregulated in Flcn-deficient hearts, and that rapamycin treatment significantly reduced heart mass and ameliorated cardiac dysfunction. Phospho-AMP-activated protein kinase (AMPK)-alpha (T172) was reduced in Flcn-deficient hearts and nonresponsive to various stimulations including metformin and AICAR (5-amino-1-beta-D-ribofuranosyl-imidazole-4-carboxamide). ATP levels were elevated and mitochondrial function was increased in Flcn-deficient hearts, suggesting that excess energy resulting from up-regulated mitochondrial metabolism under Flcn deficiency might attenuate AMPK activation. Expression of Ppargc1a, a central molecule for mitochondrial metabolism, was increased in Flcn-deficient hearts and indeed, inactivation of Ppargc1a in Flcn-deficient hearts significantly reduced heart mass and prolonged survival. Ppargc1a inactivation restored phospho-AMPK-alpha levels and suppressed mTORC1 activity in Flcn-deficient hearts, suggesting that up-regulated Ppargc1a confers increased mitochondrial metabolism and excess energy, leading to inactivation of AMPK and activation of mTORC1. Rapamycin treatment did not affect the heart size of Flcn/Ppargc1a doubly inactivated hearts, further supporting the idea that Ppargc1a is the critical element leading to deregulation of the AMPK-mTOR-axis and resulting in cardiac hypertrophy under Flcn deficiency. These data support an important role for Flcn in cardiac homeostasis in the murine model.
C1 [Hasumi, Yukiko; Baba, Masaya; Hasumi, Hisashi; Huang, Ying; Lang, Martin; Reindorf, Rachel; Oh, Hyoung-bin; Schmidt, Laura S.; Linehan, W. Marston] NCI, Urol Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Sciarretta, Sebastiano; Sadoshima, Junichi] Rutgers State Univ, New Jersey Med Sch, Dept Cell Biol & Mol Med, Newark, NJ 07101 USA.
[Nagashima, Kunio] Frederick Natl Lab Canc Res, Leidos Biomed Res Inc, Image Anal Lab, Frederick, MD 21702 USA.
[Haines, Diana C.] Frederick Natl Lab Canc Res, Leidos Biomed Res Inc, Pathol Histotechnol Lab, Frederick, MD 21702 USA.
[Schmidt, Laura S.] Frederick Natl Lab Canc Res, Leidos Biomed Res Inc, Basic Sci Program, Frederick, MD 21702 USA.
[Schneider, Michael D.] Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, Fac Med, British Heart Fdn,Ctr Res Excellence, London SW7 2AZ, England.
[Adelstein, Robert S.] NHLBI, Mol Cardiol Lab, NIH, Bethesda, MD 20892 USA.
[Sciarretta, Sebastiano] IRCCS Neuromed, I-86077 Pozzilli, IS, Italy.
RP Linehan, WM (reprint author), NCI, Urol Oncol Branch, Ctr Canc Res, NIH, 10 Ctr Dr MSC1107,CRC Room 1-5940W, Bethesda, MD 20892 USA.
EM wml@nih.gov
OI Lang, Martin/0000-0002-0242-6713; Adelstein, Robert/0000-0002-8683-2144
FU Intramural Research Program of NIH, Frederick National Lab, Center for
Cancer Research; Frederick National Laboratory for Cancer Research, NIH
[HHSN261200800001E]
FX This word was supported by the Intramural Research Program of NIH,
Frederick National Lab, Center for Cancer Research. This project has
been funded in whole or in part with federal funds from the Frederick
National Laboratory for Cancer Research, NIH, under contract
HHSN261200800001E. The content of this publication does not necessarily
reflect the views or policies of the Department of Health and Human
Services, nor does mention of trade names, commercial products or
organizations imply endorsement by the US Government.
NR 74
TC 8
Z9 8
U1 0
U2 6
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0964-6906
EI 1460-2083
J9 HUM MOL GENET
JI Hum. Mol. Genet.
PD NOV 1
PY 2014
VL 23
IS 21
BP 5706
EP 5719
DI 10.1093/hmg/ddu286
PG 14
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA AQ9UX
UT WOS:000343203600010
PM 24908670
ER
PT J
AU Ratnapriya, R
Zhan, XW
Fariss, RN
Branham, KE
Zipprer, D
Chakarova, CF
Sergeev, YV
Campos, MM
Othman, M
Friedman, JS
Maminishkis, A
Waseem, NH
Brooks, M
Rajasimha, HK
Edwards, AO
Lotery, A
Klein, BE
Truitt, BJ
Li, BS
Schaumberg, DA
Morgan, DJ
Morrison, MA
Souied, E
Tsironi, EE
Grassmann, F
Fishman, GA
Silvestri, G
Scholl, HPN
Kim, IK
Ramke, J
Tuo, JS
Merriam, JE
Merriam, JC
Park, KH
Olson, LM
Farrer, LA
Johnson, MP
Peachey, NS
Lathrop, M
Baron, RV
Igo, RP
Klein, R
Hagstrom, SA
Kamatani, Y
Martin, TM
Jiang, YD
Conley, Y
Sahel, JA
Zack, DJ
Chan, CC
Pericak-Vance, MA
Jacobson, SG
Gorin, MB
Klein, ML
Allikmets, R
Iyengar, SK
Weber, BH
Haines, JL
Leveillard, T
Deangelis, MM
Stambolian, D
Weeks, DE
Bhattacharya, SS
Chew, EY
Heckenlively, JR
Abecasis, GR
Swaroop, A
AF Ratnapriya, Rinki
Zhan, Xiaowei
Fariss, Robert N.
Branham, Kari E.
Zipprer, David
Chakarova, Christina F.
Sergeev, Yuri V.
Campos, Maria M.
Othman, Mohammad
Friedman, James S.
Maminishkis, Arvydas
Waseem, Naushin H.
Brooks, Matthew
Rajasimha, Harsha K.
Edwards, Albert O.
Lotery, Andrew
Klein, Barbara E.
Truitt, Barbara J.
Li, Bingshan
Schaumberg, Debra A.
Morgan, Denise J.
Morrison, Margaux A.
Souied, Eric
Tsironi, Evangelia E.
Grassmann, Felix
Fishman, Gerald A.
Silvestri, Giuliana
Scholl, Hendrik P. N.
Kim, Ivana K.
Ramke, Jacqueline
Tuo, Jingsheng
Merriam, Joanna E.
Merriam, John C.
Park, Kyu Hyung
Olson, Lana M.
Farrer, Lindsay A.
Johnson, Matthew P.
Peachey, Neal S.
Lathrop, Mark
Baron, Robert V.
Igo, Robert P., Jr.
Klein, Ronald
Hagstrom, Stephanie A.
Kamatani, Yoichiro
Martin, Tammy M.
Jiang, Yingda
Conley, Yvette
Sahel, Jose-Alan
Zack, Donald J.
Chan, Chi-Chao
Pericak-Vance, Margaret A.
Jacobson, Samuel G.
Gorin, Michael B.
Klein, Michael L.
Allikmets, Rando
Iyengar, Sudha K.
Weber, Bernhard H.
Haines, Jonathan L.
Leveillard, Thierry
Deangelis, Margaret M.
Stambolian, Dwight
Weeks, Daniel E.
Bhattacharya, Shomi S.
Chew, Emily Y.
Heckenlively, John R.
Abecasis, Goncalo R.
Swaroop, Anand
TI Rare and common variants in extracellular matrix gene Fibrillin 2 (FBN2)
are associated with macular degeneration
SO HUMAN MOLECULAR GENETICS
LA English
DT Article
ID ONSET RETINAL DEGENERATION; SORSBYS FUNDUS DYSTROPHY; GENOME-WIDE
ASSOCIATION; BRUCHS MEMBRANE; TISSUE INHIBITOR; HIGH-RISK;
METALLOPROTEINASES-3 TIMP3; MALATTIA LEVENTINESE; RETINITIS-PIGMENTOSA;
DRUSEN FORMATION
AB Neurodegenerative diseases affecting the macula constitute a major cause of incurable vision loss and exhibit considerable clinical and genetic heterogeneity, from early-onset monogenic disease to multifactorial late-onset age-related macular degeneration (AMD). As part of our continued efforts to define genetic causes of macular degeneration, we performed whole exome sequencing in four individuals of a two-generation family with autosomal dominant maculopathy and identified a rare variant p.Glu1144Lys in Fibrillin 2 (FBN2), a glycoprotein of the elastin-rich extracellular matrix (ECM). Sanger sequencing validated the segregation of this variant in the complete pedigree, including two additional affected and one unaffected individual. Sequencing of 192 maculopathy patients revealed additional rare variants, predicted to disrupt FBN2 function. We then undertook additional studies to explore the relationship of FBN2 to macular disease. We show that FBN2 localizes to Bruch's membrane and its expression appears to be reduced in aging and AMD eyes, prompting us to examine its relationship with AMD. We detect suggestive association of a common FBN2 non-synonymous variant, rs154001 (p.Val965Ile) with AMD in 10 337 cases and 11 174 controls (OR = 1.10; P-value = 3.79 x 10(-5)). Thus, it appears that rare and common variants in a single gene-FBN2-can contribute to Mendelian and complex forms of macular degeneration. Our studies provide genetic evidence for a key role of elastin microfibers and Bruch's membrane in maintaining blood-retina homeostasis and establish the importance of studying orphan diseases for understanding more common clinical phenotypes.
C1 [Ratnapriya, Rinki; Zipprer, David; Friedman, James S.; Brooks, Matthew; Rajasimha, Harsha K.; Swaroop, Anand] NEI, Neurobiol Neurodegenerat & Repair Lab, NIH, Bethesda, MD 20892 USA.
[Fariss, Robert N.; Campos, Maria M.] NEI, Biol Imaging Core, NIH, Bethesda, MD 20892 USA.
[Sergeev, Yuri V.] NEI, Ophthalm Genet & Visual Funct Branch, NIH, Bethesda, MD 20892 USA.
[Maminishkis, Arvydas] NEI, Sect Epithelial & Retinal Physiol & Dis, NIH, Bethesda, MD 20892 USA.
[Tuo, Jingsheng; Chan, Chi-Chao] NEI, Immunopathol Sect, NIH, Bethesda, MD 20892 USA.
[Chew, Emily Y.] NEI, Clin Trials Branch, Div Epidemiol & Clin Applicat, NIH, Bethesda, MD 20892 USA.
[Zhan, Xiaowei; Abecasis, Goncalo R.] Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA.
[Zhan, Xiaowei; Abecasis, Goncalo R.] Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA.
[Branham, Kari E.; Othman, Mohammad; Heckenlively, John R.] Univ Michigan, Dept Ophthalmol & Visual Sci, Ann Arbor, MI 48109 USA.
[Chakarova, Christina F.; Waseem, Naushin H.; Bhattacharya, Shomi S.] UCL Inst Ophthalmol, Dept Genet, London EC1V 9EL, England.
[Edwards, Albert O.] Univ Oregon, Inst Mol Biol, Eugene, OR 97401 USA.
[Edwards, Albert O.] Oregon Retina, Eugene, OR 97401 USA.
[Lotery, Andrew] Univ Southampton, Fac Med Clin & Expt Sci, Southampton SO16 6YD, Hants, England.
[Klein, Barbara E.; Klein, Ronald] Univ Wisconsin, Sch Med, Dept Ophthalmol & Visual Sci, Madison, WI 53726 USA.
[Truitt, Barbara J.; Igo, Robert P., Jr.; Iyengar, Sudha K.] Case Western Reserve Univ, Dept Epidemiol & Biostat, Cleveland, OH 44106 USA.
[Li, Bingshan; Olson, Lana M.; Haines, Jonathan L.] Vanderbilt Univ, Ctr Human Genet Res, Nashville, TN 37232 USA.
[Schaumberg, Debra A.] Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02215 USA.
[Schaumberg, Debra A.; Morgan, Denise J.; Morrison, Margaux A.; Deangelis, Margaret M.] Univ Utah, Dept Ophthalmol & Visual Sci, Moran Eye Ctr, Salt Lake City, UT 84132 USA.
[Souied, Eric] Univ Paris Est Creteil, Hop Intercommunal Creteil, Hop Henri Mondor, F-94000 Creteil, France.
[Tsironi, Evangelia E.] Univ Thessaly, Sch Med, Dept Ophthalmol, Larisa, Greece.
[Grassmann, Felix; Weber, Bernhard H.] Univ Regensburg, Inst Human Genet, D-93053 Regensburg, Germany.
[Fishman, Gerald A.] Univ Illinois, Dept Ophthalmol & Visual Sci, Chicago, IL 60607 USA.
[Silvestri, Giuliana] Queens Univ Belfast, Ctr Vis & Vasc Sci, Belfast, Antrim, North Ireland.
[Scholl, Hendrik P. N.; Zack, Donald J.] Johns Hopkins Univ, Wilmer Eye Inst, Baltimore, MD 21287 USA.
[Kim, Ivana K.] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA.
[Ramke, Jacqueline] Fred Hollows Fdn, Auckland, New Zealand.
[Ramke, Jacqueline] Univ New S Wales, Sch Social Sci, Sydney, NSW, Australia.
[Merriam, Joanna E.; Merriam, John C.; Allikmets, Rando] Columbia Univ, Dept Ophthalmol, New York, NY 10032 USA.
[Allikmets, Rando] Columbia Univ, Dept Pathol & Cell Biol, New York, NY 10032 USA.
[Park, Kyu Hyung] Seoul Natl Univ, Dept Ophthalmol, Bundang Hosp, Seoul 463707, South Korea.
[Farrer, Lindsay A.] Boston Univ, Dept Med, Sect Biomed Genet, Sch Med, Boston, MA 02215 USA.
[Farrer, Lindsay A.] Boston Univ, Dept Ophthalmol, Sect Biomed Genet, Sch Med, Boston, MA 02215 USA.
[Farrer, Lindsay A.] Boston Univ, Dept Biostat, Sch Med, Sect Biomed Genet, Boston, MA 02215 USA.
[Farrer, Lindsay A.] Boston Univ, Dept Med, Sect Biomed Genet, Sch Publ Hlth, Boston, MA 02215 USA.
[Farrer, Lindsay A.] Boston Univ, Dept Ophthalmol, Sect Biomed Genet, Sch Publ Hlth, Boston, MA 02215 USA.
[Farrer, Lindsay A.] Boston Univ, Dept Biostat, Sect Biomed Genet, Sch Publ Hlth, Boston, MA 02215 USA.
[Johnson, Matthew P.] Texas Biomed Res Inst, San Antonio, TX 78245 USA.
[Peachey, Neal S.; Hagstrom, Stephanie A.] Cleveland Clin Fdn, Cole Eye Inst, Cleveland, OH 44195 USA.
[Peachey, Neal S.] Louis Stokes Cleveland VA Med Ctr, Cleveland, OH 44195 USA.
[Lathrop, Mark; Kamatani, Yoichiro; Sahel, Jose-Alan; Leveillard, Thierry] Univ Paris 06, INSERM, Dept Genet, Inst Vis,UMR S 968, Paris, France.
[Baron, Robert V.; Weeks, Daniel E.] Univ Pittsburgh, Dept Human Genet, Grad Sch Publ Hlth, Pittsburgh, PA 15261 USA.
[Jiang, Yingda; Weeks, Daniel E.] Univ Pittsburgh, Dept Biostat, Grad Sch Publ Hlth, Pittsburgh, PA 15261 USA.
[Martin, Tammy M.] Oregon Hlth & Sci Univ, Portland, OR 97239 USA.
[Conley, Yvette] Univ Pittsburgh, Sch Nursing, Pittsburgh, PA 15261 USA.
[Pericak-Vance, Margaret A.] Univ Miami, Miller Sch Med, Bascom Palmer Eye Inst, Miami, FL 33125 USA.
[Pericak-Vance, Margaret A.] Univ Miami, Miller Sch Med, Miami, FL 33125 USA.
[Jacobson, Samuel G.] Univ Penn, Dept Ophthalmol, Scheie Eye Inst, Philadelphia, PA 19104 USA.
[Gorin, Michael B.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Ophthalmol, Los Angeles, CA 90095 USA.
[Klein, Michael L.] Univ Portland, Macular Degenerat Ctr, Casey Eye Inst, Portland, OR 97201 USA.
[Stambolian, Dwight] Univ Penn, Dept Ophthalmol, Philadelphia, PA USA.
[Stambolian, Dwight] Univ Penn, Dept Genet, Philadelphia, PA USA.
RP Swaroop, A (reprint author), NEI, Neurobiol Neurodegenerat & Repair Lab, NIH, Bethesda, MD 20892 USA.
EM swaroopa@nei.nih.gov
RI DeAngelis, e/J-7863-2015; Kamatani, Yoichiro/N-5513-2015; Sahel,
Jose-Alain/F-3172-2017;
OI Ramke, Jacqueline/0000-0002-5764-1306; Farrer,
Lindsay/0000-0001-5533-4225; Swaroop, Anand/0000-0002-1975-1141; Weeks,
Daniel/0000-0001-9410-7228
FU National Eye Institute and National Institutes of Health [EY016862,
EY013435, EY09859, EY017362, EY014458, EY019007]; Macula Vision Research
Foundation; Foundation Fighting Blindness; Kaplen Foundation; Widgeon
Point Charitable Foundation; Harold and Pauline Price Foundation; Elmer
and Sylvia Sramek Foundation; Veterans Administration; German Research
Foundation [WE 1259/19-2]; NIHR; Welcome Trust [076169/A]; American
Health Assistance Foundation [M2007110]; Frost Charitable Trust; Brian
Mercer Charitable Trust; Macular Society; Gift of Sight; Research to
Prevent Blindness
FX This study was supported by Intramural Research Program of the National
Eye Institute and National Institutes of Health grants (EY016862,
EY013435, EY09859, EY017362, EY014458, EY019007), Macula Vision Research
Foundation, Foundation Fighting Blindness, Kaplen Foundation, Widgeon
Point Charitable Foundation, Harold and Pauline Price Foundation, Elmer
and Sylvia Sramek Foundation, Veterans Administration, Harold and
Pauline Price Foundation, German Research Foundation (WE 1259/19-2),
NIHR supported BRC at Moorfields Eye Hospital (London), Welcome Trust
(076169/A), American Health Assistance Foundation (M2007110), Frost
Charitable Trust, Brian Mercer Charitable Trust, Macular Society and the
Gift of Sight, and Research to Prevent Blindness.
NR 64
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Z9 13
U1 0
U2 23
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0964-6906
EI 1460-2083
J9 HUM MOL GENET
JI Hum. Mol. Genet.
PD NOV 1
PY 2014
VL 23
IS 21
BP 5827
EP 5837
DI 10.1093/hmg/ddu276
PG 11
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA AQ9UX
UT WOS:000343203600020
PM 24899048
ER
PT J
AU Butler, EA
Hollenstein, T
Shoham, V
Rohrbaugh, MJ
AF Butler, Emily A.
Hollenstein, Tom
Shoham, Varda
Rohrbaugh, Michael J.
TI A dynamic state-space analysis of interpersonal emotion regulation in
couples who smoke
SO JOURNAL OF SOCIAL AND PERSONAL RELATIONSHIPS
LA English
DT Article
DE Dynamic sequences; interpersonal emotion regulation;
relationship-focused coping; smoking; state-space grids
ID INTERRUPTING IRONIC PROCESSES; HEALTH-COMPROMISED SMOKERS; PARENT-CHILD
INTERACTIONS; SYMPTOM-SYSTEM FIT; RELATIONSHIP SATISFACTION; MARITAL
SATISFACTION; INTIMATE PARTNERS; COMMUNITY SAMPLE; MARRIED-COUPLES;
SEX-DIFFERENCES
AB Regulating emotions in interpersonal contexts requires managing one's own emotion, a partner's emotion, and the emotional tone of the relationship (e. g., conflict and intimacy). This multifaceted regulatory challenge, often referred to as "relationship-focused coping,'' has been associated with health outcomes, but the real-time emotional processes involved are understudied. We use state-space grids (a recently developed graphical method) to investigate dynamic sequences of emotional experience (positive vs. negative) and relationship-focused coping intentions (to protect vs. engage one's partner) taken from 26 couples in which one or both partners were smokers, while they discussed a health-related disagreement during a nonsmoking baseline and then while smoking. State-space indicators of contingent emotion-coping sequences showed evidence of both successful regulation (associated with improving emotional state) and unsuccessful regulation (associated with worsening emotional state). The pattern of results suggests that interpersonal emotion regulation may interfere with smoking cessation differently depending upon whether one or both partners smoke.
C1 [Butler, Emily A.; Shoham, Varda; Rohrbaugh, Michael J.] Univ Arizona, Tucson, AZ 85721 USA.
[Hollenstein, Tom] Queens Univ, Kingston, ON K7L 3N6, Canada.
[Shoham, Varda] NIMH, Bethesda, MD USA.
RP Butler, EA (reprint author), Univ Arizona, Dept Family Studies & Human Dev, 650N Pk Ave, Tucson, AZ 85721 USA.
EM eabutler@email.arizona.edu
FU National Institute on Drug Abuse [R21-DA13121, U10-DA15815]
FX This project was supported by the National Institute on Drug Abuse
(grants R21-DA13121 and U10-DA15815).
NR 54
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U1 2
U2 20
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 0265-4075
EI 1460-3608
J9 J SOC PERS RELAT
JI J. Soc. Pers. Relatsh.
PD NOV
PY 2014
VL 31
IS 7
BP 907
EP 927
DI 10.1177/0265407513508732
PG 21
WC Communication; Family Studies; Psychology, Social
SC Communication; Family Studies; Psychology
GA AQ7NX
UT WOS:000343005800003
ER
PT J
AU Zanotti-Fregonara, P
Lyoo, CH
Bar-Hen, A
Liow, JS
Zoghbi, SS
Fujita, M
Innis, RB
AF Zanotti-Fregonara, Paolo
Lyoo, Chul Hyoung
Bar-Hen, Avner
Liow, Jeih-San
Zoghbi, Sami S.
Fujita, Masahiro
Innis, Robert B.
TI Application of calibrated image-derived input function to a clinical
protocol
SO NUCLEAR MEDICINE COMMUNICATIONS
LA English
DT Letter
ID POSITRON-EMISSION-TOMOGRAPHY; HUMAN BRAIN; PET
C1 [Zanotti-Fregonara, Paolo; Liow, Jeih-San; Zoghbi, Sami S.; Fujita, Masahiro; Innis, Robert B.] NIMH, Mol Imaging Branch, Bethesda, MD 20892 USA.
[Zanotti-Fregonara, Paolo] Univ Bordeaux, INCIA, UMR CNRS 5287, Talence, France.
[Bar-Hen, Avner] Paris Descartes Univ, Paris, France.
[Lyoo, Chul Hyoung] Yonsei Univ, Coll Med, Dept Neurol, Gangnam Severance Hosp, Seoul, South Korea.
RP Innis, RB (reprint author), NIMH, Mol Imaging Branch, 10 Ctr Dr, Bethesda, MD 20892 USA.
EM robert.innis@nih.gov
FU Intramural NIH HHS [ZIA MH002852-09]
NR 8
TC 0
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U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0143-3636
EI 1473-5628
J9 NUCL MED COMMUN
JI Nucl. Med. Commun.
PD NOV
PY 2014
VL 35
IS 11
BP 1188
EP 1189
DI 10.1097/MNM.0000000000000184
PG 2
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA AQ6CZ
UT WOS:000342897100016
PM 25238579
ER
PT J
AU Rossouw, JE
AF Rossouw, Jacques E.
TI Reconciling the Divergent Findings from Clinical Trials and
Observational Studies of Menopausal Hormone Therapy for Prevention of
Coronary Heart Disease
SO SEMINARS IN REPRODUCTIVE MEDICINE
LA English
DT Article
DE estrogen; progestin; coronary heart disease; epidemiology; clinical
trials
ID ESTROGEN PLUS PROGESTIN; RANDOMIZED CONTROLLED-TRIAL; POSTMENOPAUSAL
WOMEN; CARDIOVASCULAR-DISEASE; BENEFITS; RISKS; AGE
AB In the Women's Health Initiative (WHI) Observational study, current use of estrogen plus progestin,therapy (EPT) and estrogen therapy:showed an association with reduced risk of coronary heart disease (CHD). However, after taking into account the early increase in risk, the observational study and clinical trial hazard ratios did not differ significantly and showed no benefit for CND: These findings were confirmed in novel reanalyses for EPT use in the Nurses' Health Study which for the first time included early events and yielded results similar to those of the WHI trial in showing no CHD benefit: The underestimation of CHD risk in observational studies of Menopausal hormone therapy appears to lie in their inefficiency at capturing the early increase in risk in current users; by contrast clinical trials are very efficient at capturing early risk. Observational study data mostly reflects long-term use in women who survive the early increase, while trials mainly reflect short-term use. Confounding plays a role, but biologic differences in study populations are unlikely to explain the different risk estimates.
C1 NHLBI, Bethesda, MD 20892 USA.
RP Rossouw, JE (reprint author), NHLBI, 6701 Rockledge Dr,Room 9192, Bethesda, MD 20892 USA.
EM rossouwj@nih.gov
NR 20
TC 1
Z9 1
U1 0
U2 1
PU THIEME MEDICAL PUBL INC
PI NEW YORK
PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA
SN 1526-8004
EI 1526-4564
J9 SEMIN REPROD MED
JI Semin. Reprod. Med.
PD NOV
PY 2014
VL 32
IS 6
BP 426
EP 432
DI 10.1055/s-0034-1384625
PG 7
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA AR1RS
UT WOS:000343362900004
PM 25321419
ER
PT J
AU Ozato, K
Kamada, R
Patel, M
Fujita, T
Zhang, YB
Tamura, T
Zhu, J
AF Ozato, Keiko
Kamada, Rui
Patel, Mira
Fujita, Takashi
Zhang, Yubo
Tamura, Tomohiko
Zhu, Jun
TI Epigenetic regulation of interferon response
SO CYTOKINE
LA English
DT Meeting Abstract
CT 2nd Annual Meeting of the International-Cytokine-and-Interferon-Society
(ICIS)
CY OCT 26-29, 2014
CL Melbourne, AUSTRALIA
SP Int Cytokine & Interferon Soc
C1 [Ozato, Keiko; Kamada, Rui; Patel, Mira] NICHD, Program Genom Differentiat, NIH, Bethesda, MD USA.
[Fujita, Takashi] Kyoto Univ, Inst Virus Res, Kyoto 606, Japan.
[Zhang, Yubo; Zhu, Jun] Okohama City Univ, Sch Med, Yokohama, Kanagawa, Japan.
[Tamura, Tomohiko] NHLBI, DNA Sequencing & Computat Biol Core, NIH, Bethesda, MD USA.
RI Patel, Mira/A-3013-2015
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 1043-4666
EI 1096-0023
J9 CYTOKINE
JI Cytokine
PD NOV
PY 2014
VL 70
IS 1
MA S-19
BP 25
EP 25
DI 10.1016/j.cyto.2014.07.239
PG 1
WC Biochemistry & Molecular Biology; Cell Biology; Immunology
SC Biochemistry & Molecular Biology; Cell Biology; Immunology
GA AQ7TI
UT WOS:000343021700022
ER
PT J
AU Abdi, K
Singh, NJ
AF Abdi, Kaveh
Singh, Nevil J.
TI Distinct tissue factors bind free IL-12p40 monomer extracellularly to
generate novel cytokines
SO CYTOKINE
LA English
DT Meeting Abstract
CT 2nd Annual Meeting of the International-Cytokine-and-Interferon-Society
(ICIS)
CY OCT 26-29, 2014
CL Melbourne, AUSTRALIA
SP Int Cytokine & Interferon Soc
C1 [Abdi, Kaveh] NIAID, NIH, Rockville, MD USA.
[Singh, Nevil J.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 1043-4666
EI 1096-0023
J9 CYTOKINE
JI Cytokine
PD NOV
PY 2014
VL 70
IS 1
MA 1
BP 28
EP 28
DI 10.1016/j.cyto.2014.07.008
PG 1
WC Biochemistry & Molecular Biology; Cell Biology; Immunology
SC Biochemistry & Molecular Biology; Cell Biology; Immunology
GA AQ7TI
UT WOS:000343021700031
ER
PT J
AU Balinsky, CA
Schmeisser, H
Zoon, KC
AF Balinsky, Corey A.
Schmeisser, Hana
Zoon, Kathryn C.
TI Characterization of a novel interferon stimulated gene with antiviral
activity
SO CYTOKINE
LA English
DT Meeting Abstract
CT 2nd Annual Meeting of the International-Cytokine-and-Interferon-Society
(ICIS)
CY OCT 26-29, 2014
CL Melbourne, AUSTRALIA
SP Int Cytokine & Interferon Soc
C1 [Balinsky, Corey A.; Schmeisser, Hana; Zoon, Kathryn C.] NIAID, NIH, Bethesda, MD 20892 USA.
NR 0
TC 1
Z9 1
U1 0
U2 1
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 1043-4666
EI 1096-0023
J9 CYTOKINE
JI Cytokine
PD NOV
PY 2014
VL 70
IS 1
MA 4
BP 28
EP 29
DI 10.1016/j.cyto.2014.07.011
PG 2
WC Biochemistry & Molecular Biology; Cell Biology; Immunology
SC Biochemistry & Molecular Biology; Cell Biology; Immunology
GA AQ7TI
UT WOS:000343021700034
ER
PT J
AU Bergamaschi, C
Ng, SM
Chen, S
Bear, J
Alicea, C
Beach, RK
Sowder, R
Chertova, E
Felber, BK
Pavlakis, GN
AF Bergamaschi, Cristina
Ng, Sin-Man
Chen, Stephanie
Bear, Jenifer
Alicea, Candido
Beach, Rachel K.
Sowder, Raymond
Chertova, Elena
Felber, Barbara K.
Pavlakis, George N.
TI Heterodimeric IL-15 promotes tumor control through the regulation of the
balance of effector and regulatory cells via an IL-2 deprivation
mechanism
SO CYTOKINE
LA English
DT Meeting Abstract
CT 2nd Annual Meeting of the International-Cytokine-and-Interferon-Society
(ICIS)
CY OCT 26-29, 2014
CL Melbourne, AUSTRALIA
SP Int Cytokine & Interferon Soc
C1 [Bergamaschi, Cristina; Ng, Sin-Man; Chen, Stephanie; Bear, Jenifer; Alicea, Candido; Beach, Rachel K.; Felber, Barbara K.; Pavlakis, George N.] NCI, Vaccine Branch, Ctr Canc Res, Frederick, MD 21701 USA.
[Sowder, Raymond; Chertova, Elena] Leidos Biomed Res Inc, Retroviral Prot Chem Core, AIDS & Canc Virus Program, Frederick Natl Lab Canc Res, Frederick, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 3
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 1043-4666
EI 1096-0023
J9 CYTOKINE
JI Cytokine
PD NOV
PY 2014
VL 70
IS 1
MA 8
BP 29
EP 30
DI 10.1016/j.cyto.2014.07.015
PG 2
WC Biochemistry & Molecular Biology; Cell Biology; Immunology
SC Biochemistry & Molecular Biology; Cell Biology; Immunology
GA AQ7TI
UT WOS:000343021700038
ER
PT J
AU Bertheloot, D
Sirois, CM
Miller, AL
Jin, TC
Garbi, N
Xiao, TS
Latz, E
AF Bertheloot, Damien
Sirois, Cherilyn M.
Miller, Allison L.
Jin, Tengchuan
Garbi, Natalio
Xiao, T. Sam
Latz, Eicke
TI RAGE is a cell surface nucleic acid sensor
SO CYTOKINE
LA English
DT Meeting Abstract
CT 2nd Annual Meeting of the International-Cytokine-and-Interferon-Society
(ICIS)
CY OCT 26-29, 2014
CL Melbourne, AUSTRALIA
SP Int Cytokine & Interferon Soc
C1 [Bertheloot, Damien; Latz, Eicke] Univ Bonn, Inst Innate Immun, Bonn, Nrw, Germany.
[Sirois, Cherilyn M.] Amer Univ, Coll Hlth Sci, Ctr Translat Res, Quito, Ecuador.
[Miller, Allison L.] MedImmune LLC, Div Resp Inflammat & Autoimmun, Gaithersburg, MD USA.
[Jin, Tengchuan; Xiao, T. Sam] NIAID, Struct Immunobiol Unit, Immunol Lab, NIH, Bethesda, MD 20892 USA.
[Garbi, Natalio] Univ Bonn, Inst Mol Med, Bonn, Nrw, Germany.
[Garbi, Natalio] Univ Bonn, Inst Expt Immunol, Bonn, Nrw, Germany.
[Latz, Eicke] Univ Massachusetts, Dept Med, Sch Med, Div Infect Dis & Immunol, Worcester, MA USA.
[Latz, Eicke] Univ Bonn, German Ctr Neurodegenerat Dis, Bonn, Nrw, Germany.
NR 0
TC 0
Z9 0
U1 1
U2 5
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 1043-4666
EI 1096-0023
J9 CYTOKINE
JI Cytokine
PD NOV
PY 2014
VL 70
IS 1
MA 9
BP 30
EP 30
DI 10.1016/j.cyto.2014.07.016
PG 1
WC Biochemistry & Molecular Biology; Cell Biology; Immunology
SC Biochemistry & Molecular Biology; Cell Biology; Immunology
GA AQ7TI
UT WOS:000343021700039
ER
PT J
AU Coll, RC
Robertson, AAB
Chae, JJ
Higgins, SC
Dungan, LS
Munoz-Planillo, R
Monks, BG
Croker, DE
Sutton, CE
Stutz, A
Nunez, G
Latz, E
Kastner, DL
Mills, KHG
Masters, SL
Schroder, K
Cooper, MA
O'Neill, LAJ
AF Coll, Rebecca C.
Robertson, Avril A. B.
Chae, Jae Jin
Higgins, Sarah C.
Dungan, Lara S.
Munoz-Planillo, Raul
Monks, Brian G.
Croker, Daniel E.
Sutton, Caroline E.
Stutz, Andrea
Nunez, Gabriel
Latz, Eicke
Kastner, Daniel L.
Mills, Kingston H. G.
Masters, Seth L.
Schroder, Kate
Cooper, Matt A.
O'Neill, Luke A. J.
TI MCC950 is a potent and specific inhibitor of the NLRP3 inflammasome and
a novel potential therapeutic for NLRP3 driven diseases
SO CYTOKINE
LA English
DT Meeting Abstract
CT 2nd Annual Meeting of the International-Cytokine-and-Interferon-Society
(ICIS)
CY OCT 26-29, 2014
CL Melbourne, AUSTRALIA
SP Int Cytokine & Interferon Soc
C1 [Coll, Rebecca C.; Robertson, Avril A. B.; Croker, Daniel E.; Schroder, Kate; Cooper, Matt A.] Univ Queensland, Inst Mol Biosci, Brisbane, Qld, Australia.
[Coll, Rebecca C.; Higgins, Sarah C.; Dungan, Lara S.; Sutton, Caroline E.; Mills, Kingston H. G.; O'Neill, Luke A. J.] Univ Dublin Trinity Coll, Trinity Biomed Sci Inst, Dublin 2, Ireland.
[Chae, Jae Jin; Kastner, Daniel L.] NHGRI, Inflammatory Dis Sect, Med Genet Branch, NIH, Bethesda, MD 20892 USA.
[Munoz-Planillo, Raul; Nunez, Gabriel] Univ Michigan, Sch Med, Dept Pathol, Ann Arbor, MI 48109 USA.
[Munoz-Planillo, Raul; Nunez, Gabriel] Univ Michigan, Sch Med, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA.
[Monks, Brian G.; Stutz, Andrea; Latz, Eicke] Univ Bonn, Inst Innate Immun, Bonn, Germany.
[Masters, Seth L.] Walter & Eliza Hall Inst Med Res, Melbourne, Vic 3050, Australia.
RI Croker, Daniel/N-7134-2013; Monks, Brian/B-8362-2015; Coll,
Rebecca/J-2124-2014; Cooper, Matthew/C-7988-2009; Robertson,
Avril/A-4043-2012
OI Croker, Daniel/0000-0001-9533-4019; Monks, Brian/0000-0003-4008-3093;
Coll, Rebecca/0000-0002-7359-6023; Robertson, Avril/0000-0002-9652-8357
NR 0
TC 0
Z9 0
U1 1
U2 14
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 1043-4666
EI 1096-0023
J9 CYTOKINE
JI Cytokine
PD NOV
PY 2014
VL 70
IS 1
MA 30
BP 35
EP 35
DI 10.1016/j.cyto.2014.07.037
PG 1
WC Biochemistry & Molecular Biology; Cell Biology; Immunology
SC Biochemistry & Molecular Biology; Cell Biology; Immunology
GA AQ7TI
UT WOS:000343021700060
ER
PT J
AU Kim, ML
Chae, JJ
Stirzaker, RA
Ko, HJ
Roberts, AW
Kastner, DL
Kile, BT
Croker, BA
Masters, SL
AF Kim, Man Lyang
Chae, Jae Jin
Stirzaker, Ros A.
Ko, Hyun-Ja
Roberts, Andrew W.
Kastner, Daniel L.
Kile, Ben T.
Croker, Ben A.
Masters, Seth L.
TI Inflammasome activation due to polymerized actin triggers an
autoinflammatory disease that is dependent on IL-18, not IL-1 beta
SO CYTOKINE
LA English
DT Meeting Abstract
CT 2nd Annual Meeting of the International-Cytokine-and-Interferon-Society
(ICIS)
CY OCT 26-29, 2014
CL Melbourne, AUSTRALIA
SP Int Cytokine & Interferon Soc
C1 [Kim, Man Lyang; Stirzaker, Ros A.; Ko, Hyun-Ja; Roberts, Andrew W.; Kile, Ben T.; Masters, Seth L.] Royal Melbourne Hosp, Walter & Eliza Hall Inst Med Res, Parkville, Vic 3050, Australia.
[Chae, Jae Jin; Kastner, Daniel L.] NHGRI, Med Genet Branch, Bethesda, MD 20892 USA.
[Croker, Ben A.] Boston Childrens Hosp, Div Hematol & Oncol, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 1043-4666
EI 1096-0023
J9 CYTOKINE
JI Cytokine
PD NOV
PY 2014
VL 70
IS 1
MA 126
BP 58
EP 58
DI 10.1016/j.cyto.2014.07.133
PG 1
WC Biochemistry & Molecular Biology; Cell Biology; Immunology
SC Biochemistry & Molecular Biology; Cell Biology; Immunology
GA AQ7TI
UT WOS:000343021700156
ER
PT J
AU Onabajo, O
Porter-Gill, P
Prokunina-Olsson, L
AF Onabajo, Olusegun
Porter-Gill, Patricia
Prokunina-Olsson, Ludmila
TI Intracellular interferon lambda 4 (IFN-lambda 4) induces apoptotic cell
death in human hepatic
SO CYTOKINE
LA English
DT Meeting Abstract
CT 2nd Annual Meeting of the International-Cytokine-and-Interferon-Society
(ICIS)
CY OCT 26-29, 2014
CL Melbourne, AUSTRALIA
SP Int Cytokine & Interferon Soc
C1 [Onabajo, Olusegun; Porter-Gill, Patricia; Prokunina-Olsson, Ludmila] NCI, Lab Translat Genom, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 3
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 1043-4666
EI 1096-0023
J9 CYTOKINE
JI Cytokine
PD NOV
PY 2014
VL 70
IS 1
MA 140
BP 62
EP 62
DI 10.1016/j.cyto.2014.07.147
PG 1
WC Biochemistry & Molecular Biology; Cell Biology; Immunology
SC Biochemistry & Molecular Biology; Cell Biology; Immunology
GA AQ7TI
UT WOS:000343021700170
ER
PT J
AU Ouinn, K
Zak, D
Costa, A
Yamamoto, A
Nicosia, A
Price, D
Gall, J
Roederer, M
Aderem, A
Seder, R
AF Ouinn, Kylie
Zak, Daniel
Costa, Andreia
Yamamoto, Ayako
Nicosia, Alfredo
Price, David
Gall, Jason
Roederer, Mario
Aderem, Alan
Seder, Robert
TI CD8 T cell responses correlate with antigen but are independent of type
I IFN and STING signaling after adenoviral vaccination
SO CYTOKINE
LA English
DT Meeting Abstract
CT 2nd Annual Meeting of the International-Cytokine-and-Interferon-Society
(ICIS)
CY OCT 26-29, 2014
CL Melbourne, AUSTRALIA
SP Int Cytokine & Interferon Soc
C1 [Ouinn, Kylie] Univ Melbourne, Dept Microbiol & Immunol, Melbourne, Vic, Australia.
[Zak, Daniel; Aderem, Alan] Seattle Biomed Res Inst, Seattle, WA 98109 USA.
[Costa, Andreia; Yamamoto, Ayako; Roederer, Mario; Seder, Robert] NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA.
[Nicosia, Alfredo] Okairos, Rome, Italy.
[Price, David] Cardiff Univ, Sch Med, Cardiff CF10 3AX, S Glam, Wales.
[Gall, Jason] GenVec Inc, Gaithersburg, MD USA.
RI Price, David/C-7876-2013
OI Price, David/0000-0001-9416-2737
NR 0
TC 0
Z9 0
U1 0
U2 3
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 1043-4666
EI 1096-0023
J9 CYTOKINE
JI Cytokine
PD NOV
PY 2014
VL 70
IS 1
MA 152
BP 64
EP 65
DI 10.1016/j.cyto.2014.07.159
PG 2
WC Biochemistry & Molecular Biology; Cell Biology; Immunology
SC Biochemistry & Molecular Biology; Cell Biology; Immunology
GA AQ7TI
UT WOS:000343021700182
ER
PT J
AU Paquin, A
Onabajo, O
Porter-Gill, P
Prokunina-Olsson, L
AF Paquin, Ashley
Onabajo, Olusegun
Porter-Gill, Patricia
Prokunina-Olsson, Ludmila
TI Interferon lambda 4 (IFN-lambda 4) induces a pro-inflammatory state in
human hepatic cells which can be blocked by a monoclonal antibody
SO CYTOKINE
LA English
DT Meeting Abstract
CT 2nd Annual Meeting of the International-Cytokine-and-Interferon-Society
(ICIS)
CY OCT 26-29, 2014
CL Melbourne, AUSTRALIA
SP Int Cytokine & Interferon Soc
C1 [Paquin, Ashley; Onabajo, Olusegun; Porter-Gill, Patricia; Prokunina-Olsson, Ludmila] NCI, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 1043-4666
EI 1096-0023
J9 CYTOKINE
JI Cytokine
PD NOV
PY 2014
VL 70
IS 1
MA 151
BP 64
EP 64
DI 10.1016/j.cyto.2014.07.158
PG 1
WC Biochemistry & Molecular Biology; Cell Biology; Immunology
SC Biochemistry & Molecular Biology; Cell Biology; Immunology
GA AQ7TI
UT WOS:000343021700181
ER
PT J
AU Massilamany, C
Krishnan, B
Rajasekaran, RA
Gangaplara, A
Elowsky, C
Zhou, Y
Kuszynski, C
Reddy, J
AF Massilamany, Chandirasegaran
Krishnan, Bharathi
Rajasekaran, Rajkumar A.
Gangaplara, Arunakumar
Elowsky, Christian
Zhou, You
Kuszynski, Charles
Reddy, Jay
TI Versatility of major histocompatibility complex class II dextramers for
detection, and functional characterization of antigen-specific,
autoreactive CD4 T cells in the mouse models of autoimmune diseases
SO CYTOKINE
LA English
DT Meeting Abstract
CT 2nd Annual Meeting of the International-Cytokine-and-Interferon-Society
(ICIS)
CY OCT 26-29, 2014
CL Melbourne, AUSTRALIA
SP Int Cytokine & Interferon Soc
C1 [Massilamany, Chandirasegaran; Krishnan, Bharathi; Rajasekaran, Rajkumar A.; Gangaplara, Arunakumar; Reddy, Jay] Univ Nebraska, Sch Vet Med & Biomed Sci, Lincoln, NE USA.
[Gangaplara, Arunakumar] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA.
[Elowsky, Christian; Zhou, You] Univ Nebraska, Ctr Biotechnol, Lincoln, NE USA.
[Kuszynski, Charles] Univ Nebraska, Nebraska Ctr Virol, Lincoln, NE USA.
RI Massilamany, Chandirasegaran/D-9305-2016
OI Massilamany, Chandirasegaran/0000-0002-0205-282X
NR 0
TC 0
Z9 0
U1 0
U2 1
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 1043-4666
EI 1096-0023
J9 CYTOKINE
JI Cytokine
PD NOV
PY 2014
VL 70
IS 1
MA 157
BP 66
EP 66
DI 10.1016/j.cyto.2014.07.164
PG 1
WC Biochemistry & Molecular Biology; Cell Biology; Immunology
SC Biochemistry & Molecular Biology; Cell Biology; Immunology
GA AQ7TI
UT WOS:000343021700187
ER
PT J
AU Wink, D
AF Wink, David
TI Inflammation and nitric oxide synthase 2 in driving poor prognosis in
era(-) breast cancer
SO CYTOKINE
LA English
DT Meeting Abstract
CT 2nd Annual Meeting of the International-Cytokine-and-Interferon-Society
(ICIS)
CY OCT 26-29, 2014
CL Melbourne, AUSTRALIA
SP Int Cytokine & Interferon Soc
C1 [Wink, David] NCI, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 1043-4666
EI 1096-0023
J9 CYTOKINE
JI Cytokine
PD NOV
PY 2014
VL 70
IS 1
MA 198
BP 76
EP 76
DI 10.1016/j.cyto.2014.07.205
PG 1
WC Biochemistry & Molecular Biology; Cell Biology; Immunology
SC Biochemistry & Molecular Biology; Cell Biology; Immunology
GA AQ7TI
UT WOS:000343021700228
ER
PT J
AU Young, HA
Hanson, C
Sanford, M
Matsunaga, K
Kimoto, M
Hirao, I
AF Young, Howard A.
Hanson, Charlotte
Sanford, Michael
Matsunaga, Ken-ichiro
Kimoto, Michiko
Hirao, Ichiro
TI Inhibiting cytokine activity - The use of modified DNA aptamers as an
alternative to neutralizing antibodies
SO CYTOKINE
LA English
DT Meeting Abstract
CT 2nd Annual Meeting of the International-Cytokine-and-Interferon-Society
(ICIS)
CY OCT 26-29, 2014
CL Melbourne, AUSTRALIA
SP Int Cytokine & Interferon Soc
C1 [Young, Howard A.; Hanson, Charlotte; Sanford, Michael] NCI, Frederick, MD 21701 USA.
[Matsunaga, Ken-ichiro; Kimoto, Michiko; Hirao, Ichiro] TagCyx Biotechon, Yokohama, Kanagawa, Japan.
[Matsunaga, Ken-ichiro; Kimoto, Michiko; Hirao, Ichiro] RIKEN Ctr Life Sci Technol, Yokohama, Kanagawa, Japan.
NR 0
TC 0
Z9 0
U1 0
U2 3
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 1043-4666
EI 1096-0023
J9 CYTOKINE
JI Cytokine
PD NOV
PY 2014
VL 70
IS 1
MA 208
BP 78
EP 78
DI 10.1016/j.cyto.2014.07.215
PG 1
WC Biochemistry & Molecular Biology; Cell Biology; Immunology
SC Biochemistry & Molecular Biology; Cell Biology; Immunology
GA AQ7TI
UT WOS:000343021700238
ER
PT J
AU Golozar, A
Beaty, TH
Gravitt, PE
Ruczinski, I
Qiao, YL
Fan, JH
Ding, T
Tang, ZZ
Etemadi, A
Hu, N
Hyland, PL
Wang, LM
Wang, CY
Dawsey, SM
Freedman, ND
Abnet, CC
Goldstein, AM
Taylor, PR
AF Golozar, Asieh
Beaty, Terri H.
Gravitt, Patti E.
Ruczinski, Ingo
Qiao, You-Lin
Fan, Jin-Hu
Ding, Ti
Tang, Ze-Zhong
Etemadi, Arash
Hu, Nan
Hyland, Paula L.
Wang, Lemin
Wang, Chaoyu
Dawsey, Sanford M.
Freedman, Neal D.
Abnet, Christian C.
Goldstein, Alisa M.
Taylor, Philip R.
TI Oesophageal squamous cell carcinoma in high-risk Chinese populations:
Possible role for vascular epithelial growth factor A
SO EUROPEAN JOURNAL OF CANCER
LA English
DT Article
DE Oesophageal squamous cell carcinoma; Inflammation; Wound-healing;
Genetic marker; Genetics; Inflammation-related events; Vascular
endothelial growth factor A VEGFA
ID BREAST-CANCER RISK; NUTRITION INTERVENTION TRIALS; GENDER-SPECIFIC
ASSOCIATION; DISEASE-SPECIFIC MORTALITY; ANGIOGENIC SWITCH;
GENERAL-POPULATION; COLON-CANCER; VEGF GENE; POLYMORPHISM; EXPRESSION
AB Background: Mechanisms involved in wound healing play some role in carcinogenesis in multiple organs, likely by creating a chronic inflammatory milieu. This study sought to assess the role of genetic markers in selected inflammation-related genes involved in wound healing (interleukin (IL)-1a, IL-1b, IL-1 Receptor type I (IL-1Ra), IL-1 Receptor type II (IL-1Rb), tumour necrosis factor (TNF)-alpha, tumour necrosis factor receptor superfamily member (TNFRSF) 1A, nuclear factor kappa beta (NF-kB) 1, NF-kB2, inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2, hypoxia induced factor (HIF)-1 alpha, vascular endothelial growth factor (VEGF) A and P-53) in risk to oesophageal squamous cell carcinoma (OSCC).
Methods: We genotyped 125 tag single nucleotide polymorphism (SNP) s in 410 cases and 377 age and sex matched disease-free individuals from Nutritional Intervention Trial (NIT) cohort, and 546 cases and 556 controls individually matched for age, sex and neighbourhood from Shanxi case-control study, both conducted in high-risk areas of north-central China (1985-2007). Cox proportional-hazard models and conditional logistic regression models were used for SNPs analyses for NIT and Shanxi, respectively. Fisher's inverse test statistics were used to obtain gene-level significance.
Results: Multiple SNPs were significantly associated with OSCC in both studies, however, none retained their significance after a conservative Bonferroni adjustment. Empiric p-values for tag SNPs in VEGFA in NIT were highly concentrated in the lower tail of the distribution, suggesting this gene may be influencing risk. Permutation tests confirmed the significance of this pattern. At the gene level, VEGFA yielded an empiric significance (P = 0.027) in NIT. We also observed some evidence for interaction between environmental factors and some VEGFA tag SNPs.
Conclusion: Our finding adds further evidence for a potential role for markers in the VEGFA gene in the development and progression of early precancerous lesions of oesophagus. (c) 2014 Elsevier Ltd. All rights reserved.
C1 [Golozar, Asieh; Etemadi, Arash; Hu, Nan; Hyland, Paula L.; Wang, Lemin; Wang, Chaoyu; Dawsey, Sanford M.; Freedman, Neal D.; Abnet, Christian C.; Goldstein, Alisa M.; Taylor, Philip R.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Golozar, Asieh; Beaty, Terri H.; Gravitt, Patti E.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA.
[Ruczinski, Ingo] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD USA.
[Qiao, You-Lin; Fan, Jin-Hu] Chinese Acad Med Sci, Canc Inst Hosp, Dept Epidemiol, Beijing 100730, Peoples R China.
[Ding, Ti; Tang, Ze-Zhong] Shanxi Canc Hosp, Taiyuan, Shanxi, Peoples R China.
RP Golozar, A (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, 605 N Wolfe St,E6036, Baltimore, MD 21205 USA.
EM agolozar@jhu.edu
RI Abnet, Christian/C-4111-2015; Freedman, Neal/B-9741-2015; Etemadi,
Arash/C-1386-2016; Qiao, You-Lin/B-4139-2012
OI Abnet, Christian/0000-0002-3008-7843; Freedman,
Neal/0000-0003-0074-1098; Etemadi, Arash/0000-0002-3458-1072; Qiao,
You-Lin/0000-0001-6380-0871
FU Division of Cancer Epidemiology and Genetics, National Cancer Institute,
National Institutes of Health, United States
FX This study was supported in part by the intramural research programme of
the Division of Cancer Epidemiology and Genetics, National Cancer
Institute, National Institutes of Health, United States.
NR 44
TC 3
Z9 4
U1 0
U2 8
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0959-8049
EI 1879-0852
J9 EUR J CANCER
JI Eur. J. Cancer
PD NOV
PY 2014
VL 50
IS 16
BP 2855
EP 2865
DI 10.1016/j.ejca.2014.07.022
PG 11
WC Oncology
SC Oncology
GA AQ3NT
UT WOS:000342701500013
PM 25172294
ER
PT J
AU Litiere, S
De Vries, EGE
Seymour, L
Sargent, D
Shankar, L
Bogaerts, J
AF Litiere, S.
De Vries, E. G. E.
Seymour, L.
Sargent, D.
Shankar, L.
Bogaerts, J.
CA RECIST Comm
TI Should we resist to including tumour growth patterns in Response
Evaluation Criteria in Solid Tumours evaluation? (Response to Litiere et
al.) Reply
SO EUROPEAN JOURNAL OF CANCER
LA English
DT Letter
ID PROGRESSION; SURVIVAL
C1 [Litiere, S.; Bogaerts, J.] EORTC, Brussels, Belgium.
[De Vries, E. G. E.] Univ Groningen, Univ Med Ctr, Dept Med Oncol, Groningen, Netherlands.
[Seymour, L.] Queens Univ, NCIC Clin Trials Grp, Kingston, ON, Canada.
[Sargent, D.] Mayo Clin, Div Biomed Stat & Informat, Rochester, MN USA.
[Shankar, L.] NCI, Canc Imaging Program, NIH, Bethesda, MD 20892 USA.
RP Litiere, S (reprint author), EORTC, Brussels, Belgium.
NR 5
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 0959-8049
EI 1879-0852
J9 EUR J CANCER
JI Eur. J. Cancer
PD NOV
PY 2014
VL 50
IS 16
BP 2889
EP 2891
DI 10.1016/j.ejca.2014.08.001
PG 3
WC Oncology
SC Oncology
GA AQ3NT
UT WOS:000342701500017
PM 25219450
ER
PT J
AU Fan, RZ
Wang, YF
Mills, JL
Carter, TC
Lobach, I
Wilson, AF
Bailey-Wilson, JE
Weeks, DE
Xiong, MM
AF Fan, Ruzong
Wang, Yifan
Mills, James L.
Carter, Tonia C.
Lobach, Iryna
Wilson, Alexander F.
Bailey-Wilson, Joan E.
Weeks, Daniel E.
Xiong, Momiao
TI Generalized Functional Linear Models for Gene-Based Case-Control
Association Studies
SO GENETIC EPIDEMIOLOGY
LA English
DT Article
DE rare variants; common variants; case-control association studies;
complex diseases; logistic regression; functional data analysis;
generalized functional linear models
ID QUANTITATIVE TRAITS; TESTING ASSOCIATION; COMMON DISEASES; SEQUENCING
DATA; RARE VARIANTS; INDIVIDUALS; SNPS; SIMILARITY; REGRESSION; RISK
AB By using functional data analysis techniques, we developed generalized functional linear models for testing association between a dichotomous trait and multiple genetic variants in a genetic region while adjusting for covariates. Both fixed and mixed effect models are developed and compared. Extensive simulations show that Rao's efficient score tests of the fixed effect models are very conservative since they generate lower type I errors than nominal levels, and global tests of the mixed effect models generate accurate type I errors. Furthermore, we found that the Rao's efficient score test statistics of the fixed effect models have higher power than the sequence kernel association test (SKAT) and its optimal unified version (SKAT-O) in most cases when the causal variants are both rare and common. When the causal variants are all rare (i.e., minor allele frequencies less than 0.03), the Rao's efficient score test statistics and the global tests have similar or slightly lower power than SKAT and SKAT-O. In practice, it is not known whether rare variants or common variants in a gene region are disease related. All we can assume is that a combination of rare and common variants influences disease susceptibility. Thus, the improved performance of our models when the causal variants are both rare and common shows that the proposed models can be very useful in dissecting complex traits. We compare the performance of our methods with SKAT and SKAT-O on real neural tube defects and Hirschsprung's disease datasets. The Rao's efficient score test statistics and the global tests are more sensitive than SKAT and SKAT-O in the real data analysis. Our methods can be used in either gene-disease genome-wide/exome-wide association studies or candidate gene analyses.
C1 [Fan, Ruzong; Wang, Yifan] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Biostat & Bioinformat Branch, Div Intramural Populat Hlth Res, NIH, Bethesda, MD 20852 USA.
[Mills, James L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Intramural Populat Hlth Res, NIH, Rockville, MD 20852 USA.
[Carter, Tonia C.] Marshfield Clin Fdn Med Res & Educ, Ctr Human Genet, Marshfield, WI USA.
[Lobach, Iryna] Univ Calif San Francisco, Sch Med, Dept Epidemiol & Biostat, Div Biostat, San Francisco, CA 94143 USA.
[Wilson, Alexander F.; Bailey-Wilson, Joan E.] NHGRI, Stat Genet Sect, Computat & Stat Genom Branch, NIH, Bethesda, MD 20892 USA.
[Weeks, Daniel E.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Human Genet, Pittsburgh, PA 15261 USA.
[Weeks, Daniel E.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15261 USA.
[Xiong, Momiao] Univ Texas Houston, Ctr Human Genet, Houston, TX USA.
RP Fan, RZ (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Biostat & Bioinformat Branch, Div Intramural Populat Hlth Res, NIH, 6100 Execut Blvd,Room 7B07J,MSC 7510, Bethesda, MD 20852 USA.
EM fanr@mail.nih.gov
OI Bailey-Wilson, Joan/0000-0002-9153-2920; Weeks,
Daniel/0000-0001-9410-7228
FU Intramural Research Program of the Eunice Kennedy Shriver National
Institute of Child Health and Human Development; Intramural Research
Program of the National Human Genome Research Institute; National
Institutes of Health, Bethesda, MD; Wei Chen's NIH/NEI grant [R01
EY024226]; University of Pittsburgh
FX This study was supported by the Intramural Research Program of the
Eunice Kennedy Shriver National Institute of Child Health and Human
Development (Ruzong Fan, Yifan Wang, and James L. Mills), by the
Intramural Research Program of the National Human Genome Research
Institute (Alexander F. Wilson and Joan E. Bailey-Wilson), National
Institutes of Health, Bethesda, MD, and by Wei Chen's NIH/NEI grant R01
EY024226 (Daniel E. Weeks, Ruzong Fan is an unpaid collaborator on this
grant) and the University of Pittsburgh (Daniel E. Weeks). We thank Dr.
Goeman for many e-mail communications about the global tests developed
in his group. We thank Dr. Seunggeun Lee for sending us his simulation
program of SKAT and sequence data generated by Dr. Yun Li using program
COSI; and Dr. Yun Li for generation and LD pattern of the sequence data.
Two anonymous reviewers and the editor, Dr. Shete, provided very good
and insightful comments for us to improve the manuscript.
NR 51
TC 12
Z9 12
U1 3
U2 9
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0741-0395
EI 1098-2272
J9 GENET EPIDEMIOL
JI Genet. Epidemiol.
PD NOV
PY 2014
VL 38
IS 7
BP 622
EP 637
DI 10.1002/gepi.21840
PG 16
WC Genetics & Heredity; Mathematical & Computational Biology
SC Genetics & Heredity; Mathematical & Computational Biology
GA AQ4UN
UT WOS:000342795300005
PM 25203683
ER
PT J
AU Oldekamp, S
Pscheidl, S
Kress, E
Soehnlein, O
Jansen, S
Pufe, T
Wang, JM
Tauber, SC
Brandenburg, LO
AF Oldekamp, Sandra
Pscheidl, Sebastian
Kress, Eugenia
Soehnlein, Oliver
Jansen, Sandra
Pufe, Thomas
Wang, Ji Ming
Tauber, Simone C.
Brandenburg, Lars-Ove
TI Lack of formyl peptide receptor 1 and 2 leads to more severe
inflammation and higher mortality in mice with of pneumococcal
meningitis
SO IMMUNOLOGY
LA English
DT Article
DE bacterial meningitis; formyl peptide receptor; glia cell; innate
immunity; Streptococcus pneumoniae
ID 1-42-INDUCED SIGNAL-TRANSDUCTION; N-FORMYLPEPTIDE RECEPTOR;
CENTRAL-NERVOUS-SYSTEM; TOLL-LIKE RECEPTORS; BACTERIAL-MENINGITIS;
GLIAL-CELLS; NEURODEGENERATIVE DISEASES; IMMUNE-RESPONSES; CXC
CHEMOKINES; HOST-DEFENSE
AB Bacterial meningitis is, despite progress in research and the development of new treatment strategies, still a cause of severe neuronal sequelae. The brain is protected from penetrating pathogens by both the blood-brain barrier and the innate immune system. The invading pathogens are recognized by pattern recognition receptors including the G-protein coupled formyl peptide receptors (FPRs), which are expressed by immune cells of the central nervous system. The expression of FPRs is up-regulated during bacterial meningitis, but the consequence on the progression of inflammation and impact on mortality are far from clear. Therefore, we used mFPR1 and mFPR2-deficient mice to investigate the effects on inflammation, bacterial growth and mortality in a mouse model of pneumococcal meningitis. Our results revealed increased bacterial burden, increased neutrophil infiltration and higher mortality in mFPR1/2-deficient mice in comparison to wild-type mice. The mFPR1- or mFPR2-deficient mice also showed significantly increased glial cell density, whereas the immune responses including the expression of anti-inflammatory cytokines and antimicrobial peptides were decreased in bacterial meningitis. Taken together, the results suggest that FPR1 and FPR2 play an important role in the innate immune responses against Streptococcus pneumoniae within the central nervous system and the lack of the receptors leads to a dysregulation of the inflammatory response compared with wild-type mice.
C1 [Oldekamp, Sandra; Pscheidl, Sebastian; Kress, Eugenia; Jansen, Sandra; Pufe, Thomas; Brandenburg, Lars-Ove] Rhein Westfal TH Aachen, Dept Anat & Cell Biol, D-52074 Aachen, Germany.
[Soehnlein, Oliver] Ludwig Maximilians Univ Munchen, Inst Cardiovasc Prevent, Munich, Germany.
[Wang, Ji Ming] NCI, Mol Immunoregulat Lab, Canc & Inflammat Program, Ctr Canc Res, Frederick, MD 21701 USA.
[Tauber, Simone C.] RWTH Univ Hosp Aachen, Dept Neurol, Aachen, Germany.
RP Brandenburg, LO (reprint author), Rhein Westfal TH Aachen, Dept Anat & Cell Biol, Wendlingweg 2, D-52074 Aachen, Germany.
EM stauber@ukaa-chen.de; lbranden-burg@ukaachen.de
FU Else Kroner-Fresenius-Stiftung; START-Programme of the RWTH Aachen
University; National Cancer Institute, NIH, USA
FX SO and SP designed and performed experiments. EK and SJ helped to
accomplish experiments. OS and JMW provided the mice and helped to draft
the manuscript. TP co-conceived of the study and helped to draft the
manuscript. SCJ helped to accomplish experiments and revised the
manuscript. L-OB designed as well as performed experiments, and drafted
the manuscript. We thank Susanne Echterhagen, Lian Shen, Michaela
Nicolau and Sabine Hamm for excellent technical assistance. This study
was supported by the Else Kroner-Fresenius-Stiftung (L-OB) and the
START-Programme of the RWTH Aachen University (SCT and L-OB). JMW was
supported by intramural research support programme of National Cancer
Institute, NIH, USA.
NR 49
TC 10
Z9 11
U1 0
U2 10
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0019-2805
EI 1365-2567
J9 IMMUNOLOGY
JI Immunology
PD NOV
PY 2014
VL 143
IS 3
BP 447
EP 461
DI 10.1111/imm.12324
PG 15
WC Immunology
SC Immunology
GA AQ6CB
UT WOS:000342894300014
PM 24863484
ER
PT J
AU Glaus, J
Vandeleur, CL
von Kanel, R
Lasserre, AM
Strippoli, MPF
Gholam-Rezaee, M
Castelao, E
Marques-Vidal, P
Bovet, P
Merikangas, K
Mooser, V
Waeber, G
Vollenweider, P
Aubry, JM
Preisig, M
AF Glaus, Jennifer
Vandeleur, Caroline L.
von Kaenel, Roland
Lasserre, Aurelie M.
Strippoli, Marie-Pierre F.
Gholam-Rezaee, Mehdi
Castelao, Enrique
Marques-Vidal, Pedro
Bovet, Pascal
Merikangas, Kathleen
Mooser, Vincent
Waeber, Gerard
Vollenweider, Peter
Aubry, Jean-Michel
Preisig, Martin
TI Associations between mood, anxiety or substance use disorders and
inflammatory markers after adjustment for multiple covariates in a
population-based study
SO JOURNAL OF PSYCHIATRIC RESEARCH
LA English
DT Article
DE C-Reactive protein; Pro-inflammatory cytokines; Mood disorders;
Depression subtypes; Anxiety disorders; Substance use disorders
ID C-REACTIVE PROTEIN; NONMELANCHOLIC MAJOR DEPRESSION; CARDIOVASCULAR
RISK-FACTORS; TEST-RETEST RELIABILITY; CORONARY-HEART-DISEASE;
GENETIC-STUDIES DIGS; DIAGNOSTIC INTERVIEW; BIPOLAR DISORDER; ATYPICAL
DEPRESSION; HEALTH BEHAVIORS
AB Inflammation is one possible mechanism underlying the associations between mental disorders and cardiovascular diseases (CVD). However, studies on mental disorders and inflammation have yielded inconsistent results and the majority did not adjust for potential confounding factors. We examined the associations of several pro-inflammatory cytokines (IL-1 beta, IL-6 and TNF-alpha) and high sensitive C-reactive protein (hsCRP) with lifetime and current mood, anxiety and substance use disorders (SUD), while adjusting for multiple covariates. The sample included 3719 subjects, randomly selected from the general population, who underwent thorough somatic and psychiatric evaluations. Psychiatric diagnoses were made with a semi-structured interview. Major depressive disorder was subtyped into "atypical", "melancholic", "combined atypical-melancholic" and "unspecified". Associations between inflammatory markers and psychiatric diagnoses were assessed using multiple linear and logistic regression models. Lifetime bipolar disorders and atypical depression were associated with increased levels of hsCRP, but not after multivariate adjustment. After multivariate adjustment, SUD remained associated with increased hsCRP levels in men (beta = 0.13 (95% CI: 0.03,0.23)) but not in women. After multivariate adjustment, lifetime combined and unspecified depression were associated with decreased levels of IL-6 (beta = 0.27 (-0.51,-0.02); beta = 0.19 (-0.34,-0.05), respectively) and TNIF-alpha (beta = 0.16 (-030,-0.01); beta= 0.10 (-0.19,-0.02), respectively), whereas current combined and unspecified depression were associated with decreased levels of hsCRP (beta = 0.20 (-0.39,-0.02); 13 = 0.12 (-0.24,-0.01), respectively). Our data suggest that the significant associations between increased hsCRP levels and mood disorders are mainly attributable to the effects of comorbid disorders, medication as well as behavioral and physical CVRFs. (C) 2014 Elsevier Ltd. All rights reserved.
C1 [Glaus, Jennifer; Vandeleur, Caroline L.; Lasserre, Aurelie M.; Strippoli, Marie-Pierre F.; Gholam-Rezaee, Mehdi; Castelao, Enrique; Preisig, Martin] Univ Lausanne Hosp, Dept Psychiat, CH-1008 Prilly, Switzerland.
[Glaus, Jennifer; Aubry, Jean-Michel] Univ Geneva, Dept Mental Hlth & Psychiat, CH-1211 Geneva 4, Switzerland.
[von Kaenel, Roland] Univ Hosp Bern, Inselspital, Div Psychosomat Med, Bern, Switzerland.
[von Kaenel, Roland] Univ Bern, CH-3012 Bern, Switzerland.
[Marques-Vidal, Pedro; Bovet, Pascal] Univ Lausanne Hosp, Inst Social & Prevent Med, CH-1008 Prilly, Switzerland.
[Merikangas, Kathleen] NIMH, Intramural Res Program, Genet Epidemiol Res Branch, Bethesda, MD 20892 USA.
[Mooser, Vincent] Univ Lausanne, Fac Biol & Med, CH-1015 Lausanne, Switzerland.
[Waeber, Gerard; Vollenweider, Peter] Univ Lausanne Hosp, Dept Internal Med, CH-1008 Prilly, Switzerland.
RP Glaus, J (reprint author), Univ Lausanne Hosp, Ctr Res Psychiat Epidemiol & Psychopathol CEPP, Dept Psychiat, Site Cery, CH-1008 Prilly, Switzerland.
EM Jennifer.Glaus@chuv.ch
RI Strippoli, Marie-Pierre/K-8164-2013; Colaus, PsyColaus/K-6607-2013;
Bovet, Pascal/F-4477-2011; Glaus, Jennifer/C-7887-2017;
OI Castelao, Enrique/0000-0003-1966-3683; Strippoli,
Marie-Pierre/0000-0003-3053-484X; Bovet, Pascal/0000-0002-0242-4259;
Glaus, Jennifer/0000-0001-8883-9473; Lasserre, Aurelie
M/0000-0003-3925-6663
FU Swiss National Science Foundation [32003B-105993, 32003B-118308,
33CSC0-122661]; GlaxoSmithKline Clinical Genetics
FX This research was supported by three grants from the Swiss National
Science Foundation (#32003B-105993, #32003B-118308 and #33CSC0-122661 to
M. Preisig) and two grants from GlaxoSmithKline Clinical Genetics to G.
Waeber, P. Vollenweiderand M. Preisig. The funding organization played
no role in the design or conduct of the study, the collection,
management, analysis, or interpretation of the data; or the preparation,
review, or approval of the manuscript.
NR 55
TC 8
Z9 8
U1 3
U2 12
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0022-3956
EI 1879-1379
J9 J PSYCHIATR RES
JI J. Psychiatr. Res.
PD NOV
PY 2014
VL 58
BP 36
EP 45
DI 10.1016/j.jpsychires.2014.07.012
PG 10
WC Psychiatry
SC Psychiatry
GA AQ5RL
UT WOS:000342866200006
PM 25088287
ER
PT J
AU Ballard, ED
Ionescu, DF
Voort, JLV
Niciu, MJ
Richards, EM
Luckenbaugh, DA
Brutsche, NE
Ameli, R
Furey, ML
Zarate, CA
AF Ballard, Elizabeth D.
Ionescu, Dawn F.
Voort, Jennifer L. Vande
Niciu, Mark J.
Richards, Erica M.
Luckenbaugh, David A.
Brutsche, Nancy E.
Ameli, Rezvan
Furey, Maura L.
Zarate, Carlos A., Jr.
TI Improvement in suicidal ideation after ketamine infusion: Relationship
to reductions in depression and anxiety
SO JOURNAL OF PSYCHIATRIC RESEARCH
LA English
DT Article
DE Ketamine; Suicide; Depression; Suicidal ideation
ID RESISTANT MAJOR DEPRESSION; D-ASPARTATE ANTAGONIST; RAPID ANTIDEPRESSANT
RESPONSE; RANDOMIZED CONTROLLED-TRIAL; ADD-ON TRIAL;
EMERGENCY-DEPARTMENT; BIPOLAR DEPRESSION; DISORDER; RISK; HOPELESSNESS
AB Objective: Suicide is a psychiatric emergency. Currently, there are no approved pharmacologic treatments for suicidal ideation. Ketamine is an N-methyl-D-aspartate (NMDA) receptor antagonist that rapidly reduces suicidal ideation as well as depression and anxiety, but the dynamic between these symptoms is not known. The aim of this analysis was to evaluate whether ketamine has an impact on suicidal thoughts, independent of depressive and anxiety symptoms.
Methods: 133 patients with treatment-resistant depression (major depressive disorder or bipolar I/II disorder) received a single subanesthetic infusion of ketamine (0.5 mg/kg over 40 min). Post-hoc correlations and linear mixed models evaluated the relationship between suicidal ideation and depression and anxiety symptoms using the Hamilton Depression Rating Scale (HAMD), Scale for Suicidal Ideation (SSI), Beck Depression Inventory (BDI), and Hamilton Anxiety Rating Scale (HAMA) focusing on 230 min post-infusion.
Results: At 230 min post-infusion, correlations between changes in suicidal ideation and depression ranged from 0.23 to 0.44 (p <.05), accounting for up to 19% in the variance of ideation change. Correlations with anxiety ranged from 0.23 to 0.40 (p <.05), accounting for similar levels of variance. Ketamine infusion was associated with significant reductions in suicidal ideation compared to placebo, when controlling for the effects of ketamine on depression (F-1,F-587 = 10.31, p =.001) and anxiety (F-1,F-567 = 8.54, p =.004).
Conclusions: Improvements in suicidal ideation after ketamine infusion are related to, but not completely driven by, improvements in depression and anxiety. Investigation of the specific effects of ketamine on suicidal thoughts is warranted. Published by Elsevier Ltd.
C1 [Ballard, Elizabeth D.; Ionescu, Dawn F.; Voort, Jennifer L. Vande; Niciu, Mark J.; Richards, Erica M.; Luckenbaugh, David A.; Brutsche, Nancy E.; Ameli, Rezvan; Furey, Maura L.; Zarate, Carlos A., Jr.] Natl Inst Mental Hlth, Intramural Res Program, Expt Therapeut & Pathophysiol Branch, NIH, Bethesda, MD 20892 USA.
RP Ballard, ED (reprint author), Bldg 10,CRC Room 7-5541,10 Ctr Dr,MSC 1282, Bethesda, MD 20892 USA.
EM Elizabeth.Ballard@nih.gov
RI Niciu, Mark/J-1766-2014; Ionescu, Dawn/K-5675-2015
OI Niciu, Mark/0000-0002-5612-3021;
FU The National Institute of Mental Health, National Institutes of Health
(IRP-NIMH-NIH)
FX The National Institute of Mental Health, National Institutes of Health
(IRP-NIMH-NIH) funded this study, but had no role in the study design or
analysis.
NR 52
TC 36
Z9 37
U1 4
U2 28
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0022-3956
EI 1879-1379
J9 J PSYCHIATR RES
JI J. Psychiatr. Res.
PD NOV
PY 2014
VL 58
BP 161
EP 166
DI 10.1016/j.jpsychires.2014.07.027
PG 6
WC Psychiatry
SC Psychiatry
GA AQ5RL
UT WOS:000342866200023
PM 25169854
ER
PT J
AU Niciu, MJ
Luckenbaugh, DA
Ionescu, DF
Richards, EM
Voort, JLV
Ballard, ED
Brutsche, NE
Furey, ML
Zarate, CA
AF Niciu, Mark J.
Luckenbaugh, David A.
Ionescu, Dawn F.
Richards, Erica M.
Voort, Jennifer L. Vande
Ballard, Elizabeth D.
Brutsche, Nancy E.
Furey, Maura L.
Zarate, Carlos A., Jr.
TI Riluzole likely lacks antidepressant efficacy in ketamine non-responders
SO JOURNAL OF PSYCHIATRIC RESEARCH
LA English
DT Letter
DE Major depressive disorder; Treatment-resistant depression; Ketamine;
Riluzole; Glutamate
ID OPEN-LABEL TRIAL; DEPRESSIVE SYMPTOMS
C1 [Niciu, Mark J.; Luckenbaugh, David A.; Ionescu, Dawn F.; Richards, Erica M.; Voort, Jennifer L. Vande; Ballard, Elizabeth D.; Brutsche, Nancy E.; Furey, Maura L.; Zarate, Carlos A., Jr.] NIMH, ETPB, NIH, Bethesda, MD 20892 USA.
RP Niciu, MJ (reprint author), NIMH, ETPB, NIH, 10 Ctr Dr,Bldg 10-CRC,Room 7-5545, Bethesda, MD 20892 USA.
EM mark.niciu@nih.gov
RI Niciu, Mark/J-1766-2014; Ionescu, Dawn/K-5675-2015
OI Niciu, Mark/0000-0002-5612-3021;
FU Intramural NIH HHS [Z99 MH999999]
NR 10
TC 8
Z9 8
U1 0
U2 4
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0022-3956
EI 1879-1379
J9 J PSYCHIATR RES
JI J. Psychiatr. Res.
PD NOV
PY 2014
VL 58
BP 197
EP 199
DI 10.1016/j.jpsychires.2014.07.022
PG 3
WC Psychiatry
SC Psychiatry
GA AQ5RL
UT WOS:000342866200028
PM 25139008
ER
PT J
AU Houghton, PJ
Kurmasheva, RT
Lyalin, D
Maris, JM
Kolb, EA
Gorlick, R
Reynolds, CP
Kang, MH
Keir, ST
Wu, J
Smith, MA
AF Houghton, Peter J.
Kurmasheva, Raushan T.
Lyalin, Dmitry
Maris, John M.
Kolb, E. Anders
Gorlick, Richard
Reynolds, C. Patrick
Kang, Min H.
Keir, Stephen T.
Wu, Jianrong
Smith, Malcolm A.
TI Initial Solid Tumor Testing (Stage 1) of AZD1480, an Inhibitor of Janus
Kinases 1 and 2 by the Pediatric Preclinical Testing Program
SO PEDIATRIC BLOOD & CANCER
LA English
DT Article
DE developmental therapeutics; JAK1; 2 inhibitor; preclinical testing
ID LARGE-CELL LYMPHOMA; ANAPLASTIC LYMPHOMA; IN-VITRO; STAT3 STABILITY;
JAK2 INHIBITOR; GROWTH; ALK; ACTIVATION; IDENTIFICATION; CONTRIBUTES
AB BackgroundAZD1480 is an ATP competitive inhibitor of Janus kinases 1 and 2 (JAK1, 2) that has been shown to inhibit the growth of solid tumor models. This agent was selected for testing the putative role of JAK/STAT signaling in the standard PPTP solid tumor models.
ProceduresAZD1480 was tested against the PPTP in vitro cell line panel at concentrations from 1.0nM to 10M and against the PPTP in vivo solid tumor xenograft panels at (60mg/kg once daily (SID)x5) for three consecutive weeks. Additional studies evaluated 5 to 20mg/kg BIDx5 with SID dosing at 7-30mg/kg at weekends for three consecutive weeks.
ResultsIn vitro the median relative IC50 (rIC(50)) for the PPTP cell lines was 1.5 mu M, with a range from 0.3 mu M to 5.9 mu M. The two cell lines with rIC(50) values of 0.3 mu M both had ALK activating genomic alterations. AZD1480 demonstrated statistically significant differences (P<0.05) in EFS distribution compared to control in 89% of the solid tumor xenografts. AZD1480 induced intermediate (EFS T/C>2) or high-level growth inhibition in 15 of 30 (50%) solid tumor xenografts. Tumor regressions were observed in three of six Wilms tumor models at doses that induced inhibition of Stat3(Y705) phosphorylation.
ConclusionsAZD1480 demonstrated significant tumor growth inhibition against most PPTP solid tumor xenografts, similar to that observed for antiangiogenic agents tested by the PPTP. Tumor regressing activity was noted for Wilms tumor xenografts. Pediatr Blood Cancer 2014;61:1972-1979. (c) 2014 Wiley Periodicals, Inc.
C1 [Houghton, Peter J.; Kurmasheva, Raushan T.; Lyalin, Dmitry] Nationwide Childrens Hosp, Columbus, OH 43205 USA.
[Maris, John M.] Univ Penn, Childrens Hosp Philadelphia, Sch Med, Philadelphia, PA 19104 USA.
[Maris, John M.] Abramson Family Canc Res Inst, Philadelphia, PA USA.
[Kolb, E. Anders] Alfred I DuPont Hosp Children, Wilmington, DE USA.
[Gorlick, Richard] Childrens Hosp Montefiore, Bronx, NY USA.
[Reynolds, C. Patrick; Kang, Min H.] Texas Tech Univ, Hlth Sci Ctr, Lubbock, TX 79430 USA.
[Keir, Stephen T.] Duke Univ, Med Ctr, Durham, NC USA.
[Wu, Jianrong] St Jude Childrens Res Hosp, Memphis, TN 38105 USA.
[Smith, Malcolm A.] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA.
RP Houghton, PJ (reprint author), Nationwide Childrens Hosp, Ctr Childhood Canc Blood Dis, 700 Childrens Dr, Columbus, OH 43205 USA.
EM Peter.Houghton@nationwidechildrens.org
OI Reynolds, C. Patrick/0000-0002-2827-8536
FU National Cancer Institute [NO1-CM-42216, CA21765, CA108786]
FX This work was supported by NO1-CM-42216, CA21765, and CA108786 from the
National Cancer Institute and used AZD1480 supplied the Astrazeneca. In
addition to the authors this paper represents work contributed by the
following: Sherry Ansher, Joshua Courtright, Kathryn Evans, Edward
Favours, Henry S. Friedman, Danuta Gasinski, Doris A. Phelps, Melissa
Sammons, Joe Zeidner, Jianrong Wu, Ellen Zhang, and Jian Zhang.
NR 39
TC 3
Z9 3
U1 0
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 NOV
PY 2014
VL 61
IS 11
BP 1972
EP 1979
DI 10.1002/pbc.25175
PG 8
WC Oncology; Hematology; Pediatrics
SC Oncology; Hematology; Pediatrics
GA AQ3WD
UT WOS:000342723300012
PM 25131802
ER
PT J
AU McCuskee, S
Brickley, EB
Wood, A
Mossialos, E
AF McCuskee, Sarah
Brickley, Elizabeth B.
Wood, Angela
Mossialos, Elias
TI Malaria and Macronutrient Deficiency as Correlates of Anemia in Young
Children: A Systematic Review of Observational Studies
SO ANNALS OF GLOBAL HEALTH
LA English
DT Review
DE anemia; children; malaria; stunting; undernutrition; wasting
ID PLASMODIUM-FALCIPARUM INFECTION; CROSS-SECTIONAL SURVEY; AFRICAN
CHILDREN; DEVELOPING-COUNTRIES; PRESCHOOL-CHILDREN; IRON-DEFICIENCY;
WESTERN KENYA; MALNUTRITION; PARASITEMIA; TRIAL
AB Background: Anemia is a leading cause of pediatric mortality and impaired development and is highly prevalent in young children in sub-Saharan Africa. Populations most affected by anemia also often are at high risk for malaria and macronutrient deficiency, conditions that may exacerbate anemia. Due to its multifactorial etiology, anemia presents a significant global health challenge, and successful interventions targeting anemia require a greater understanding of the relative and interacting contributions of malaria and undernutrition.
Objectives: The aim of this study was to assess the associations of malaria and undernutrition, indicated by stunting and wasting, with anemia in young children using a systematic review of observational studies.
Methods: Searches were conducted in MEDLINE and Scopus. Articles were screened and reviewed for inclusion by two reviewers. Studies published after 1990 that measured anemia, Plasmodium falciparum malaria, and stunting or wasting in children aged 5 years or under were included.
Findings: Of 620 articles reviewed, 15 studies from 9 countries in sub-Saharan Africa were included. Statistical approaches and anemia measurement varied widely, so synthesis was qualitative. Thirteen studies found that malaria infection was associated with anemia or lowered hemoglobin; in these studies, malaria accounted for more of the variation in anemia than nutritional status. In contrast, only 7 of the 13 studies investigating stunting and 3 of the 6 studies investigating wasting as correlates of anemia observed statistically significant associations at alpha = 0.05. The role of nutrition in anemia may differ by country.
Conclusions: Observational epidemiologic studies consistently demonstrate that malaria is an important correlate of anemia in young children; however, the roles of stunting and wasting and interactions between malaria and nutrition require further investigation. Based on the current evidence, these findings suggest that global health strategies to reduce the burden of anemia should prioritize malaria prevention and support research on alternative causes of anemia that reflect local conditions.
C1 [McCuskee, Sarah; Mossialos, Elias] Univ London London Sch Econ & Polit Sci, LSE Hlth, London WC2A 2AE, England.
[Brickley, Elizabeth B.] NIAID, NIH, Bethesda, MD 20892 USA.
[Brickley, Elizabeth B.; Wood, Angela] Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England.
RP McCuskee, S (reprint author), Univ London London Sch Econ & Polit Sci, LSE Hlth, Houghton St, London WC2A 2AE, England.
EM smccuskee@post.harvard.edu
FU National Institutes of Health Oxford-Cambridge Scholars Program;
Intramural Research Program of the National Institute of Allergy and
Infectious Diseases
FX During the period of this work, EBB was supported by the National
Institutes of Health Oxford-Cambridge Scholars Program and the
Intramural Research Program of the National Institute of Allergy and
Infectious Diseases.
NR 31
TC 2
Z9 2
U1 2
U2 5
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 2014
VL 80
IS 6
BP 458
EP 465
DI 10.1016/j.aogh.2015.01.003
PG 8
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA CZ4RC
UT WOS:000367089400006
PM 25960095
ER
PT J
AU Lv, B
Zhao, H
Bai, X
Huang, SP
Fan, ZY
Lu, JH
Tang, R
Yin, KS
Gao, P
Liu, BL
Cheng, JL
AF Lv, Bei
Zhao, Hong
Bai, Xue
Huang, Shaoping
Fan, Zhenyu
Lu, Jihua
Tang, Rong
Yin, Keshan
Gao, Peter
Liu, Baoling
Cheng, Jilin
TI Entecavir Promotes CD34(+) Stem Cell Proliferation in the Peripheral
Blood and Liver of Chronic Hepatitis B and Liver Cirrhosis Patients
SO DISCOVERY MEDICINE
LA English
DT Article
ID HEPATOCELLULAR-CARCINOMA; ANTIVIRAL THERAPY; HISTOLOGICAL IMPROVEMENT;
AUTOLOGOUS INFUSION; RISK; HEPATOCYTES; EXPRESSION; FIBROSIS; DISEASES;
CD133(+)
AB Entecavir (ETV) has been used for more than 2 decades in treating hepatitis B virus (HBV) infections. It has shown significant anti-HBV effect and has led to histological improvement in the liver of chronic hepatitis B (CHB) patients. In patients treated with ETV for over two years, reversal of cirrhosis to normal tissue has also been observed. However, the mechanisms of these tissue repairing or recovery processes are not yet clear. In order to determine the roles that bone marrow and liver stem/progenitor cells play in these processes, we evaluated the CD34(+) and CD133(+) stem/progenitor cells in peripheral blood from 292 patients and liver tissues from 43 patients who had received therapies with and without ETV. A significant increase in both CD34(+) and CD133(+) cells was found in CHB and cirrhosis patients compared to the healthy controls. In patients treated with ETV, CD34(+) cells increased 2 and 4 fold in peripheral blood and liver tissues, respectively, while their CD4(+) and CD8(+) cells remained the same. On the other hand, CD133(+) cells did not change or even slightly decreased with ETV treatment. Results from immunohistochemistry staining, real time RT-PCR, and the enzyme-linked immunosorbent assay also revealed the same level of CD34(+) cell increase and CD133(+) cell decrease (or no change) in ETV treated patients, compared to patients without ETV therapies. Liver functions in patients with ETV treatment improved in general, but one liver cirrhosis patient with high expression of CD133 in liver tissue developed hepatocellular carcinoma (HCC). In summary, ETV may have differential effects on various stem cell subtypes. ETV-activated stem cells in bone marrow and liver tissues may contribute to the recovery from injuries caused by HBV infection. They also contribute to the regeneration of normal tissue and the recovery of normal liver function. Meanwhile, ETV does not activate stem cells that may participate in the initiation of HCC.
C1 [Lv, Bei; Huang, Shaoping; Fan, Zhenyu; Lu, Jihua; Tang, Rong; Yin, Keshan; Cheng, Jilin] Fudan Univ, Dept Gastroenterol, Shanghai Publ Hlth Clin Ctr, Shanghai 200433, Peoples R China.
[Zhao, Hong] Wenzhou Med Coll, Dept Gastroenterol, Wenzhou, Peoples R China.
[Bai, Xue] Jiamusi Univ, Jiamusi Med Coll, Dept Gastroenterol, Jiamusi, Peoples R China.
[Gao, Peter] NIAAA, Div Metab & Hlth Effects, NIH, Rockville, MD 20852 USA.
[Liu, Baoling] Univ Michigan, Dept Surg, Ann Arbor, MI 48109 USA.
RP Liu, BL (reprint author), Univ Michigan, Dept Surg, Ann Arbor, MI 48109 USA.
EM baoling_liu@yahoo.com; jilincheng@gmail.com
FU Chinese 12th Five-Year Plan for a special study fund on hepatitis B and
AIDS [2013ZX10004216-001-001]; Shanghai Science and Technology Committee
[124119a7801]
FX We are grateful to Dr. Yanling Feng and to Dr. Chengli Qiu for their
generous help in the pathology and flow cytometry experiments. The study
was supported by the Chinese 12th Five-Year Plan for a special study
fund on hepatitis B and AIDS (2013ZX10004216-001-001) and the Biological
Medicine Guide Fund of Shanghai Science and Technology Committee
(124119a7801).
NR 33
TC 0
Z9 1
U1 3
U2 6
PU DISCOVERY MEDICINE
PI TIMONIUM
PA 10 GERARD AVE, STE 201, TIMONIUM, MD 21093 USA
SN 1539-6509
EI 1944-7930
J9 DISCOV MED
JI Discov. Med.
PD NOV
PY 2014
VL 18
IS 100
BP 227
EP 236
PG 10
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA CB0KZ
UT WOS:000349316100001
PM 25425463
ER
PT J
AU Sierra-Madero, JG
Ellenberg, SS
Rassool, MS
Tierney, A
Belaunzaran-Zamudio, PF
Lopez-Martinez, A
Pineirua-Menendez, A
Montaner, LJ
Azzoni, L
Benitez, CR
Sereti, I
Andrade-Villanueva, J
Mosqueda-Gomez, JL
Rodriguez, B
Sanne, I
Lederman, MM
AF Sierra-Madero, Juan G.
Ellenberg, Susan S.
Rassool, Mohammed S.
Tierney, Ann
Belaunzaran-Zamudio, Pablo F.
Lopez-Martinez, Alondra
Pineirua-Menendez, Alicia
Montaner, Luis J.
Azzoni, Livio
Rivera Benitez, Cesar
Sereti, Irini
Andrade-Villanueva, Jaime
Mosqueda-Gomez, Juan L.
Rodriguez, Benigno
Sanne, Ian
Lederman, Michael M.
CA CADIRIS Study Team
TI Effect of the CCR5 antagonist maraviroc on the occurrence of immune
reconstitution inflammatory syndrome in HIV (CADIRIS): a double-blind,
randomised, placebo-controlled trial
SO LANCET HIV
LA English
DT Article
ID POTENT ANTIRETROVIRAL THERAPY; CD4(+) T-CELLS; HIV-1-INFECTED PATIENTS;
INFECTED PATIENTS; NAIVE SUBJECTS; TUBERCULOSIS; MORTALITY; PREVENTION;
INTENSIFICATION; PARTICIPANTS
AB Background Immune reconstitution inflammatory syndrome (IRIS) is a common complication of antiretroviral therapy (ART) in patients with HIV. IRIS is associated with an increased risk of admission to hospital and death. We assessed whether CCR5 blockade with maraviroc reduces the risk of IRIS.
Methods The CADIRIS study was a double-blind, randomised, placebo-controlled trial that recruited participants from five clinical sites in Mexico and one in South Africa and followed them for 1 year. Patients were eligible if they were adults with HIV, who were naive to ART, had CD4 count lower than 100 cells per mu L and HIV RNA greater than 1000 copies per mL. Participants were randomly assigned (1: 1) by permuted block randomisation to receive either maraviroc (600 mg twice daily) or placebo in addition to an ART regimen that included tenofovir, emtricitabine, and efavirenz for 48 weeks. Patients, care providers, and members of the research team were masked to treatment allocation. Clinical and laboratory evaluations were done at baseline, and weeks 2, 4, 8, 12, 16, 24, 48, and 60. The primary outcome was time to an IRIS event by 24 weeks. All patients who were randomly assigned contributed to the primary time-to-event analysis from the date of ART initiation until week 24, the time of an IRIS event or death. This trial is registered with ClinicalTrials.gov, number NCT00988780.
Findings Between Dec 10, 2009, and Jan 17, 2012, we screened 362 patients; of whom 279 met the inclusion criteria and three refused to participate; thus 276 participants were randomly assigned (140 to receive maraviroc and 136 to receive placebo) .64 (23%) patients had IRIS events, 33 (24%) in the maraviroc group and 31 (23%) in the placebo group (p = 0.74). No difference in the time to IRIS events was noted between the treatment groups (HR 1.08, 95% CI 0.66-1.77; log-rank test p = 0.74). 37 participants (26%) in the maraviroc group had grade 3 or 4 adverse events compared with 24 (18%) in placebo group; p = 0.072); 25 (18%) in the maraviroc group and 21 (15%) in the placebo group had serious treatment emergent adverse events (p = 0.63).
Interpretation Maraviroc had no significant effect on development of IRIS after ART initiation. Inclusion of this CCR5 inhibitor in an initial treatment regimen does not confer a meaningful protection from the occurrence of IRIS in people with advanced HIV infection.
C1 [Sierra-Madero, Juan G.; Belaunzaran-Zamudio, Pablo F.; Lopez-Martinez, Alondra; Pineirua-Menendez, Alicia] Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Dept Infectol, Mexico City 14000, DF, Mexico.
[Ellenberg, Susan S.; Tierney, Ann] Univ Penn, Perelman Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA.
[Rassool, Mohammed S.; Sanne, Ian] Univ Witwatersrand, Fac Hlth Sci, Dept Internal Med, Clin HIV Res Unit, Johannesburg, South Africa.
[Montaner, Luis J.; Azzoni, Livio] Wistar Inst Anat & Biol, HIV Immunopathogenesis Lab 1, Philadelphia, PA 19104 USA.
[Rivera Benitez, Cesar] Hosp Gen Mexico City, Serv Infectol, Mexico City, DF, Mexico.
[Sereti, Irini] NIAID, HIV Pathogenesis Unit, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA.
[Andrade-Villanueva, Jaime] Hosp Civil Guadalajara, Unidad VIH, Guadalajara, Jalisco, Mexico.
[Mosqueda-Gomez, Juan L.] Ctr Ambulatorio Prevenc & Atenc SIDA & Infecc Tra, Guanajuato, Mexico.
[Rodriguez, Benigno; Lederman, Michael M.] Case Western Reserve Univ, Ctr AIDS Res, Cleveland, OH 44106 USA.
RP Belaunzaran-Zamudio, PF (reprint author), Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Dept Infectol, Vasco de Quiroga 15, Mexico City 14000, DF, Mexico.
EM p_belaunzaran@yahoo.co.uk
RI Rodriguez, Benigno/C-3365-2009
OI Rodriguez, Benigno/0000-0001-9736-7957
FU Pfizer, New York, NY, USA; Intramural Research Program of NIAID/NIH
FX The trial was funded as investigator initiated research by Pfizer, New
York, NY, USA. The work of ISe was supported by the
Intramural Research Program of NIAID/NIH.
NR 45
TC 13
Z9 13
U1 0
U2 1
PU ELSEVIER INC
PI SAN DIEGO
PA 525 B STREET, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 2352-3018
J9 LANCET HIV
JI Lancet HIV
PD NOV
PY 2014
VL 1
IS 2
BP E60
EP E67
DI 10.1016/S2352-3018(14)70027-X
PG 8
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA CU8JY
UT WOS:000363789800007
PM 26366430
ER
PT J
AU Cardone, G
Duda, RL
Cheng, NQ
You, L
Conway, JF
Hendrix, RW
Steven, AC
AF Cardone, Giovanni
Duda, Robert L.
Cheng, Naiqian
You, Lili
Conway, James F.
Hendrix, Roger W.
Steven, Alasdair C.
TI Metastable Intermediates as Stepping Stones on the Maturation Pathways
of Viral Capsids
SO MBIO
LA English
DT Article
ID X-RAY CRYSTALLOGRAPHY; CRYOELECTRON MICROSCOPY; PROTEOLYTIC CLEAVAGE;
MOLECULAR-DYNAMICS; RNA VIRUS; IN-VITRO; CRYO-EM; PROTEIN; EXPANSION;
BINDING
AB As they mature, many capsids undergo massive conformational changes that transform their stability, reactivity, and capacity for DNA. In some cases, maturation proceeds via one or more intermediate states. These structures represent local minima in a rich energy landscape that combines contributions from subunit folding, association of subunits into capsomers, and intercapsomer interactions. We have used scanning calorimetry and cryo-electron microscopy to explore the range of capsid conformations accessible to bacteriophage HK97. To separate conformational effects from those associated with covalent crosslinking (a stabilization mechanism of HK97), a cross-link-incompetent mutant was used. The mature capsid Head I undergoes an endothermic phase transition at 60 degrees C in which it shrinks by 7%, primarily through changes in its hexamer conformation. The transition is reversible, with a half-life of similar to 3 min; however, >50% of reverted capsids are severely distorted or ruptured. This observation implies that such damage is a potential hazard of large-scale structural changes such as those involved in maturation. Assuming that the risk is lower for smaller changes, this suggests a rationalization for the existence of metastable intermediates: that they serve as stepping stones that preserve capsid integrity as it switches between the radically different conformations of its precursor and mature states.
IMPORTANCE Large-scale conformational changes are widespread in virus maturation and infection processes. These changes are accompanied by the release of conformational free energy as the virion (or fusogenic glycoprotein) switches from a precursor state to its mature state. Each state corresponds to a local minimum in an energy landscape. The conformational changes in capsid maturation are so radical that the question arises of how maturing capsids avoid being torn apart. Offering proof of principle, severe damage is inflicted when a bacteriophage HK97 capsid reverts from the (nonphysiological) state that it enters when heated past 60 degrees C. We suggest that capsid proteins have been selected in part by the criterion of being able to avoid sustaining collateral damage as they mature. One way of achieving this-as with the HK97 capsid-involves breaking the overall transition down into several smaller steps in which the risk of damage is reduced.
C1 [Cardone, Giovanni; Cheng, Naiqian; You, Lili; Steven, Alasdair C.] NIAMSD, Struct Biol Res Lab, Bethesda, MD 20892 USA.
[Duda, Robert L.; Hendrix, Roger W.] Univ Pittsburgh, Dept Biol Sci, Pittsburgh, PA 15260 USA.
[Conway, James F.] Univ Pittsburgh, Sch Med, Dept Biol Struct, Pittsburgh, PA USA.
RP Steven, AC (reprint author), NIAMSD, Struct Biol Res Lab, Bethesda, MD 20892 USA.
EM stevena@mail.nih.gov
FU NIAMS; NIH [R01 GM047795]
FX This work was supported by the Intramural Research Program of NIAMS and
by NIH grant R01 GM047795 to R.W.H.
NR 52
TC 1
Z9 1
U1 1
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 2014
VL 5
IS 6
AR e02067-14
DI 10.1128/mBio.02067-14
PG 9
WC Microbiology
SC Microbiology
GA AX7CE
UT WOS:000347073600037
PM 25389177
ER
PT J
AU Ambady, P
Warren, K
Shih, J
Kreisl, T
Fine, H
AF Ambady, Prakash
Warren, Katherine
Shih, Joanna
Kreisl, Teri
Fine, Howard
TI A RANDOMIZED PHASE II TRIAL OF VANDETANIB IN COMBINATION WITH
CARBOPLATIN VERSUS CARBOPLATIN ALONE FOLLOWED BY VANDETANIB ALONE IN
ADULTS WITH RECURRENT ANAPLASTIC ASTROCYTOMA
SO NEURO-ONCOLOGY
LA English
DT Meeting Abstract
CT 19th Annual Scientific Meeting of the Society-for-Neuro-Oncology (SNO)
CY NOV 13-16, 2014
CL Miami, FL
SP Soc Neuro Oncol
C1 [Ambady, Prakash; Warren, Katherine; Shih, Joanna; Kreisl, Teri; Fine, Howard] NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 1
U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1522-8517
EI 1523-5866
J9 NEURO-ONCOLOGY
JI Neuro-Oncology
PD NOV
PY 2014
VL 16
SU 5
MA AT-04
DI 10.1093/neuonc/nou237.4
PG 1
WC Oncology; Clinical Neurology
SC Oncology; Neurosciences & Neurology
GA CC6CM
UT WOS:000350452200034
ER
PT J
AU Ambady, P
Kreisl, T
Warren, K
McNeill, K
Fine, H
AF Ambady, Prakash
Kreisl, Teri
Warren, Katherine
McNeill, Katherine
Fine, Howard
TI PHASE I TRIAL OF ENZASTAURIN (LY 317615) IN COMBINATION WITH CARBOPLATIN
IN ADULTS WITH RECURRENT GLIOMA
SO NEURO-ONCOLOGY
LA English
DT Meeting Abstract
CT 19th Annual Scientific Meeting of the Society-for-Neuro-Oncology (SNO)
CY NOV 13-16, 2014
CL Miami, FL
SP Soc Neuro Oncol
C1 [Ambady, Prakash; Kreisl, Teri; Warren, Katherine; McNeill, Katherine; Fine, Howard] NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 1
U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1522-8517
EI 1523-5866
J9 NEURO-ONCOLOGY
JI Neuro-Oncology
PD NOV
PY 2014
VL 16
SU 5
MA AT-03
DI 10.1093/neuonc/nou237.3
PG 1
WC Oncology; Clinical Neurology
SC Oncology; Neurosciences & Neurology
GA CC6CM
UT WOS:000350452200033
ER
PT J
AU Sutiwisesak, R
Kitiyanant, N
Kotchabhakdi, N
Felsenfeld, G
Andrews, PW
Wongtrakoongate, P
AF Sutiwisesak, Rujapope
Kitiyanant, Narisorn
Kotchabhakdi, Naiphinich
Felsenfeld, Gary
Andrews, Peter W.
Wongtrakoongate, Patompon
TI Induced pluripotency enables differentiation of human nullipotent
embryonal carcinoma cells N2102Ep
SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
LA English
DT Article
DE Embryonal carcinoma cell; Induced pluripotency; Nullipotency
ID STEM-CELLS; RETINOIC ACID; RNA INTERFERENCE; SURFACE-ANTIGENS;
GENE-EXPRESSION; RECEPTOR-GAMMA; SOMATIC-CELLS; TERATOCARCINOMA;
HYBRIDS; TUMORS
AB Embryonal carcinoma (EC) cells, which are considered to be malignant counterparts of embryonic stem cells, comprise the pluripotent stem cell component of teratocarcinomas, a form of testicular germ cell tumors (GCTs). Nevertheless, many established human EC cell lines are nullipotent with limited or no capacity to differentiate under normal circumstances. In this study, we tested whether an over-expression of Yamanaka's reprogramming factors OCT4, SOX2, c-MYC and KLF4 might enable differentiation of the human nullipotent EC cells N2102Ep. Using OCT4 knockdown differentiated N2102Ep cells, we are able to derive reprogrammed N2102Ep cell lines. The induced pluripotency of N2102Ep allows the cells to differentiate toward neural lineage by retinoic acid; the expression of SSEA3 and SSEA4 is down-regulated, whereas that of neural surface markers is up-regulated. Consistent with the up-regulation of neural surface markers, the expression of the master neuroectodermal transcription factor PAX6 is also induced in reprogrammed N2102Ep. We next investigated whether PAX6 might induce spontaneous differentiation of nullipotent stem cells N2102Ep. However, while an ectopic expression of PAX6 promotes differentiation of NTERA2, it induces cell death in N2102Ep. We nevertheless find that upon induction of retinoic add, the reprogrammed N2102Ep cells form mature neuronal morphology similar to differentiated pluripotent stem cells NTERA2 as determined by TUJ1 expression, which is absent in N2102Ep parental cells. Altogether, we conclude that the nullipotent state of human EC cells can be reprogrammed to acquire a more relaxed state of differentiation potential by Yamanaka's factors. (C) 2014 Elsevier B.V. All rights reserved.
C1 [Sutiwisesak, Rujapope; Kotchabhakdi, Naiphinich] Mahidol Univ, Inst Mol Biosci, Neurosci Res Ctr, Salaya 73170, Nakhonpathom, Thailand.
[Sutiwisesak, Rujapope; Felsenfeld, Gary; Wongtrakoongate, Patompon] NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
[Kitiyanant, Narisorn] Mahidol Univ, Stem Cell Res Grp, Inst Mol Biosci, Salaya 73170, Nakhonpathom, Thailand.
[Andrews, Peter W.; Wongtrakoongate, Patompon] Univ Sheffield, Ctr Stem Cell Biol, Sheffield S10 2TN, S Yorkshire, England.
RP Wongtrakoongate, P (reprint author), NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
EM p.wongtrakoongate@gmail.com
RI Kitiyanant, Narisorn/C-1979-2008
OI Kitiyanant, Narisorn/0000-0002-7105-9283
FU Thai Commission on Higher Education; Medical Scholars Program of Mahidol
University; Intramural Research Program of the NIH; National Institute
of Diabetes and Digestive and Kidney Diseases (NIDDK)
FX We thank Prof. Su-Chun Zhang for providing a PAX6-containing plasmid and
the CSCB tissue culture team for preparation of MEFs. PW was supported
by the Thai Commission on Higher Education. RS was a recipient of the
Medical Scholars Program of Mahidol University. This research is
supported in part by the Intramural Research Program of the NIH, The
National Institute of Diabetes and Digestive and Kidney Diseases
(NIDDK).
NR 46
TC 1
Z9 1
U1 0
U2 6
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0167-4889
EI 0006-3002
J9 BBA-MOL CELL RES
JI Biochim. Biophys. Acta-Mol. Cell Res.
PD NOV
PY 2014
VL 1843
IS 11
BP 2611
EP 2619
DI 10.1016/j.bbamcr.2014.07.013
PG 9
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA AQ1FR
UT WOS:000342527800024
PM 25086345
ER
PT J
AU Zsengeller, ZK
Aljinovic, N
Teot, LA
Korson, M
Rodig, N
Sloan, JL
Venditti, CP
Berry, GT
Rosen, S
AF Zsengeller, Zsuzsanna K.
Aljinovic, Nika
Teot, Lisa A.
Korson, Mark
Rodig, Nancy
Sloan, Jennifer L.
Venditti, Charles P.
Berry, Gerard T.
Rosen, Seymour
TI Methylmalonic acidemia: A megamitochondrial disorder affecting the
kidney
SO PEDIATRIC NEPHROLOGY
LA English
DT Article
DE Methylmalonic acidemia; Methylmalonyl-CoA mutase; Megamitochondria;
Cytochrome c oxidase; End stage renal disease; Functional electron
microscopy; Vitamin B12
ID CYTOCHROME-OXIDASE; ACIDURIA; MITOCHONDRIA; MUTATIONS; MUT(-); RATS;
IDENTIFICATION; NEPHROTOXICITY; DEFICIENCY; ACIDOSIS
AB Classical (or isolated) methylmalonic acidemia (MMA) is a heterogeneous inborn error of metabolism most typically caused by mutations in the vitamin B12-dependent enzyme methylmalonyl-CoA mutase (MUT). With the improved survival of individuals with MMA, chronic kidney disease has become recognized as part of the disorder. The precise description of renal pathology in MMA remains uncertain.
Light microscopy, histochemical, and ultrastructural studies were performed on the native kidney obtained from a 19-year-old patient with mut MMA who developed end stage renal disease and underwent a combined liver-kidney transplantation.
The light microscopy study of the renal parenchyma in the MMA kidney revealed extensive interstitial fibrosis, chronic inflammation, and tubular atrophy. Intact proximal tubules were distinguished by the widespread formation of large, circular, pale mitochondria with diminished cristae. Histochemical preparations showed a reduction of cytochrome c oxidase and NADH activities, and the electron microscopy analysis demonstrated loss of cytochrome c enzyme activity in these enlarged mitochondria.
Our results demonstrate that the renal pathology of MMA is characterized by megamitochondria formation in the proximal tubules in concert with electron transport chain dysfunction. Our findings suggest therapies that target mitochondrial function as a treatment for the chronic kidney disease of MMA.
C1 [Zsengeller, Zsuzsanna K.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
[Zsengeller, Zsuzsanna K.; Aljinovic, Nika; Rosen, Seymour] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02215 USA.
[Teot, Lisa A.; Rosen, Seymour] Harvard Univ, Sch Med, Boston Childrens Hosp, Dept Pathol, Boston, MA 02215 USA.
[Korson, Mark] Tufts Univ, Sch Med, Boston, MA 02111 USA.
[Rodig, Nancy] Harvard Univ, Sch Med, Boston Childrens Hosp, Div Nephrol, Boston, MA 02115 USA.
[Sloan, Jennifer L.; Venditti, Charles P.] NHGRI, Organ Acid Res Sect, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA.
[Berry, Gerard T.] Harvard Univ, Sch Med, Boston Childrens Hosp, Manton Ctr Orphan Dis Res, Boston, MA USA.
RP Zsengeller, ZK (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Pathol, 330 Brookline Ave, Boston, MA 02215 USA.
EM zzsengel@bidmc.harvard.edu
OI Berry, Gerard/0000-0001-5299-3313
NR 36
TC 9
Z9 11
U1 0
U2 11
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0931-041X
EI 1432-198X
J9 PEDIATR NEPHROL
JI Pediatr. Nephrol.
PD NOV
PY 2014
VL 29
IS 11
BP 2139
EP 2146
DI 10.1007/s00467-014-2847-y
PG 8
WC Pediatrics; Urology & Nephrology
SC Pediatrics; Urology & Nephrology
GA AQ0FG
UT WOS:000342457700012
PM 24865477
ER
PT J
AU Qin, N
de Cubas, AA
Garcia-Martin, R
Richter, S
Peitzsch, M
Menschikowski, M
Lenders, JWM
Timmers, HJLM
Mannelli, M
Opocher, G
Economopoulou, M
Siegert, G
Chavakis, T
Pacak, K
Robledo, M
Eisenhofer, G
AF Qin, Nan
de Cubas, Aguirre A.
Garcia-Martin, Ruben
Richter, Susan
Peitzsch, Mirko
Menschikowski, Mario
Lenders, Jacques W. M.
Timmers, Henri J. L. M.
Mannelli, Massimo
Opocher, Giuseppe
Economopoulou, Matina
Siegert, Gabriele
Chavakis, Triantafyllos
Pacak, Karel
Robledo, Mercedes
Eisenhofer, Graeme
TI Opposing effects of HIF1 alpha and HIF2 alpha on chromaffin cell
phenotypic features and tumor cell proliferation: Insights from
MYC-associated factor X
SO INTERNATIONAL JOURNAL OF CANCER
LA English
DT Article
DE pheochromocytoma and paraganglioma; phenylethanolamine
N-methyltransferase; MAX; HIF1 alpha; HIF2 alpha
ID HYPOXIA-INDUCIBLE FACTOR; TYROSINE-HYDROXYLASE; SDH MUTATIONS; PC12
CELLS; C-MYC; SPORADIC PHEOCHROMOCYTOMA; TRANSCRIPTIONAL ACTIVITY; MAX
MUTATIONS; EXPRESSION; HIF-2-ALPHA
AB Pheochromocytomas and paragangliomas (PPGLs) are catecholamine-producing chromaffin cell tumors with diverse phenotypic features reflecting mutations in numerous genes, including MYC-associated factor X (MAX). To explore whether phenotypic differences among PPGLs reflect a MAX-mediated mechanism and opposing influences of hypoxia-inducible factor (HIF)s HIF2 alpha and HIF1 alpha, we combined observational investigations in PPGLs and gene-manipulation studies in two pheochromocytoma cell lines. Among PPGLs from 140 patients, tumors due to MAX mutations were characterized by gene expression profiles and intermediate phenotypic features that distinguished these tumors from other PPGLs, all of which fell into two expression clusters: one cluster with low expression of HIF2 alpha and mature phenotypic features and the other with high expression of HIF2 alpha and immature phenotypic features due to mutations stabilizing HIFs. Max-mutated tumors distributed to a distinct subcluster of the former group. In cell lines lacking Max, re-expression of the gene resulted in maturation of phenotypic features and decreased cell cycle progression. In cell lines lacking Hif2 alpha, overexpression of the gene led to immature phenotypic features, failure of dexamethasone to induce differentiation and increased proliferation. HIF1 alpha had opposing actions to HIF2 alpha in both cell lines, supporting evolving evidence of their differential actions on tumorigenic processes via a MYC/MAX-related pathway. Requirement of a fully functional MYC/MAX complex to facilitate differentiation explains the intermediate phenotypic features in tumors due to MAX mutations. Overexpression of HIF2 alpha in chromaffin cell tumors due to mutations affecting HIF stabilization explains their proliferative features and why the tumors fail to differentiate even when exposed locally to adrenal steroids.
C1 [Qin, Nan; Richter, Susan; Peitzsch, Mirko; Menschikowski, Mario; Siegert, Gabriele; Chavakis, Triantafyllos; Eisenhofer, Graeme] Tech Univ Dresden, Inst Clin Chem & Lab Med, D-01307 Dresden, Germany.
[de Cubas, Aguirre A.; Robledo, Mercedes] Spanish Natl Canc Res Ctr CNIO, Hereditary Endocrine Canc Grp, Madrid, Spain.
[de Cubas, Aguirre A.; Robledo, Mercedes] ISCIII Ctr Biomed Res Rare Dis CIBERER, Madrid, Spain.
[Garcia-Martin, Ruben; Chavakis, Triantafyllos] Tech Univ Dresden, Dept Clin Pathobiochem, D-01307 Dresden, Germany.
[Lenders, Jacques W. M.; Chavakis, Triantafyllos; Eisenhofer, Graeme] Tech Univ Dresden, Med Clin 3, D-01307 Dresden, Germany.
[Lenders, Jacques W. M.; Timmers, Henri J. L. M.] Radboud Univ Nijmegen, Med Ctr, NL-6525 ED Nijmegen, Netherlands.
[Mannelli, Massimo] Univ Florence, Dept Expt & Clin Biomed Sci, Florence, Italy.
[Opocher, Giuseppe] Veneto Inst Oncol IRCCS, Familial Canc Clin & Oncoendocrinol, Padua, Italy.
[Opocher, Giuseppe] Univ Padua, Dept Med, Padua, Italy.
[Economopoulou, Matina] Tech Univ Dresden, Dept Ophthalmol, D-01307 Dresden, Germany.
[Pacak, Karel] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD USA.
RP Qin, N (reprint author), Tech Univ Dresden, Inst Clin Chem & Lab Med, D-01307 Dresden, Germany.
EM nan.qin@uniklinikum-dresden.de
RI Lenders, J.W.M./L-4487-2015; Robledo, Mercedes/O-2230-2013
OI Robledo, Mercedes/0000-0001-6256-5902
FU Deutsche Forschungsgemeinschaft (Microenvironment of the Adrenal) [EI
855/1-1, 252/0]; European Union [259735]; Fondo de Investigaciones
Sanitarias [PI11/01359]; European Science Foundation
(Research-Networking Program) [5925]
FX Grant sponsor: Deutsche Forschungsgemeinschaft (Microenvironment of the
Adrenal); Grant number: EI 855/1-1, 252/0; Grant sponsor: European Union
Seventh Framework Programme (Project ENS@T-Cancer); Grant number:
FP7/2007-2013 (under grant agreement no. 259735); Grant sponsor: Fondo
de Investigaciones Sanitarias; Grant number: Project PI11/01359; Grant
sponsor: European Science Foundation (Research-Networking Program);
Grant number: Reference 5925
NR 52
TC 11
Z9 11
U1 1
U2 9
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 NOV 1
PY 2014
VL 135
IS 9
BP 2054
EP 2064
DI 10.1002/ijc.28868
PG 11
WC Oncology
SC Oncology
GA AP3NU
UT WOS:000341983700011
PM 24676840
ER
PT J
AU Kievit, FM
Florczyk, SJ
Leung, MC
Wang, K
Wu, JD
Silber, JR
Ellenbogen, RG
Lee, JSH
Zhang, MQ
AF Kievit, Forrest M.
Florczyk, Stephen J.
Leung, Matthew C.
Wang, Kui
Wu, Jennifer D.
Silber, John R.
Ellenbogen, Richard G.
Lee, Jerry S. H.
Zhang, Miqin
TI Proliferation and enrichment of CD133(+) glioblastoma cancer stem cells
on 3D chitosan-alginate scaffolds
SO BIOMATERIALS
LA English
DT Article
DE Brain tumor initiating cells; Epithelial-to-mesenchymal transition;
Hyaluronic acid; Microenvironment
ID TUMOR-INITIATING CELLS; HYALURONAN-CD44 INTERACTIONS; BREAST-CANCER;
SELF-RENEWAL; T-CELLS; GROWTH; TUMORIGENICITY; CHALLENGES; CULTURE;
NOTCH
AB Emerging evidence implicates cancer stem cells (CSCs) as primary determinants of the clinical behavior of human cancers, representing an ideal target for next-generation anti-cancer therapies. However CSCs are difficult to propagate in vitro, severely limiting the study of CSC biology and drug development. Here we report that growing cells from glioblastoma (GEM) cell lines on three dimensional (3D) porous chitosan-alginate (CA) scaffolds dramatically promotes the proliferation and enrichment of cells possessing the hallmarks of CSCs. CA scaffold-grown cells were found more tumorigenic in nude mouse xenografts than cells grown from monolayers. Growing in CA scaffolds rapidly promoted expression of genes involved in the epithelial-to-mesenchymal transition that has been implicated in the genesis of CSCs. Our results indicate that CA scaffolds have utility as a simple and inexpensive means to cultivate CSCs in vitro in support of studies to understand CSC biology and develop more effective anti-cancer therapies. (C) 2014 Elsevier Ltd. All rights reserved.
C1 [Kievit, Forrest M.; Silber, John R.; Ellenbogen, Richard G.; Zhang, Miqin] Univ Washington, Dept Neurol Surg, Seattle, WA 98195 USA.
[Florczyk, Stephen J.; Leung, Matthew C.; Wang, Kui; Zhang, Miqin] Univ Washington, Dept Mat Sci & Engn, Seattle, WA 98195 USA.
[Wu, Jennifer D.] Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA.
[Wu, Jennifer D.] Med Univ S Carolina, Hollings Canc Ctr, Dept Microbiol & Immunol, Charleston, SC 29425 USA.
[Ellenbogen, Richard G.] Univ Washington, Dept Radiol, Seattle, WA 98195 USA.
[Lee, Jerry S. H.] Johns Hopkins Univ, Dept Chem & Biomol Engn, Baltimore, MD 21218 USA.
[Lee, Jerry S. H.] NCI, Ctr Strateg Sci Initiat, NIH, Bethesda, MD 20892 USA.
RP Zhang, MQ (reprint author), Univ Washington, Dept Mat Sci & Engn, 302L Roberts Hall,Box 352120, Seattle, WA 98195 USA.
EM mzhang@u.washington.edu
RI Zhang, Miqin/F-5537-2010;
OI Zhang, Miqin/0000-0001-8974-1494; Lee, Jerry/0000-0003-1515-0952;
Kievit, Forrest/0000-0002-9847-783X
FU National Institutes of Health [R01CA172455]; NIH training grant
[T32CA138312]; American Brain Tumor Association Fellowship; Egtvedt
Fellowship
FX This work was supported by National Institutes of Health grant
R01CA172455. FK acknowledges support from an NIH training grant
(T32CA138312) and an American Brain Tumor Association Fellowship in
Honor of Susan Kramer. SJF acknowledges support from the Egtvedt
Fellowship. We acknowledge the use of the SEM at the Dept. of Materials
Science and Engineering, the confocal and optical microscopes at Keck
Microscopy Imaging Facility, and the flow cytometers at the Dept. of
Immunology at the University of Washington. We acknowledge laboratory
assistance from Ms. Allison M. Lewis and Ms. Samara K. Sytsma in
preparing CA scaffolds. We thank Prof. Benjamin S. Glick for submitting
the RFP plasmid to AddGene.
NR 33
TC 18
Z9 18
U1 6
U2 77
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0142-9612
EI 1878-5905
J9 BIOMATERIALS
JI Biomaterials
PD NOV
PY 2014
VL 35
IS 33
BP 9137
EP 9143
DI 10.1016/j.biomaterials.2014.07.037
PG 7
WC Engineering, Biomedical; Materials Science, Biomaterials
SC Engineering; Materials Science
GA AO9KK
UT WOS:000341674400011
PM 25109438
ER
PT J
AU Robey, A
Buckingham-Howes, S
Salmeron, BJ
Black, MM
Riggins, T
AF Robey, Alison
Buckingham-Howes, Stacy
Salmeron, Betty Jo
Black, Maureen M.
Riggins, Tracy
TI Relations among prospective memory, cognitive abilities, and brain
structure in adolescents who vary in prenatal drug exposure
SO JOURNAL OF EXPERIMENTAL CHILD PSYCHOLOGY
LA English
DT Article
DE Prospective memory; Prenatal drug exposure; Adolescence; Executive
functioning; Retrospective memory; Brain structure
ID HUMAN CEREBRAL-CORTEX; ROSTRAL PREFRONTAL CORTEX; MAGNETIC-RESONANCE
IMAGES; SUBSTANCE-ABUSING WOMEN; SURFACE-BASED ANALYSIS; COCAINE
EXPOSURE; CORTICAL SURFACE; LIFE-SPAN; EVERYDAY MEMORY; GEOMETRICALLY
ACCURATE
AB This investigation examined how prospective memory (PM) relates to cognitive abilities (i.e., executive function, attention, working memory, and retrospective memory) and brain structure in adolescents who vary in prenatal drug exposure (PDE). The sample consisted of 105 (55 female and 50 male) urban, primarily African American adolescents (mean age = 15.5 years) from low socioeconomic status (SES) families. Approximately 56% (n = 59) were prenatally exposed to drugs (heroin and/or cocaine) and 44% (n = 46) were not prenatally exposed, but the adolescents were similar in age, gender, race, and SES. Executive functioning, attentional control, working memory, retrospective memory, and overall cognitive ability were assessed by validated performance measures. Executive functioning was also measured by caregiver report. A subset of 52 adolescents completed MRI (magnetic resonance imaging) scans, which provided measures of subcortical gray matter volumes and thickness of prefrontal, parietal, and temporal cortices. Results revealed no differences in PM performance by PDE status, even after adjusting for age and IQ Executive function, retrospective memory, cortical thickness in frontal and parietal regions, and volume of subcortical regions (i.e., putamen and hippocampus) were related to PM performance in the sample overall, even after adjusting for age, IQ and total gray matter volume. Findings suggest that variations in PM ability during adolescence are robustly related to individual differences in cognitive abilities, in particular executive function and retrospective memory, and brain structure, but do not vary by PDE status. (C) 2014 Elsevier Inc. All rights reserved.
C1 [Robey, Alison; Riggins, Tracy] Univ Maryland, Dept Psychol, College Pk, MD 20742 USA.
[Buckingham-Howes, Stacy; Black, Maureen M.] Univ Maryland, Sch Med, Baltimore, MD 20201 USA.
[Salmeron, Betty Jo] NIDA, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
RP Riggins, T (reprint author), Univ Maryland, Dept Psychol, College Pk, MD 20742 USA.
EM riggins@umd.edu
RI Salmeron, Betty Jo/M-1793-2016
OI Salmeron, Betty Jo/0000-0003-1699-9333
FU Intramural NIH HHS; NIDA NIH HHS [R01 DA021059, DA029113, F32 DA036274,
R01 DA007432, R01 DA07432, R03 DA029113]
NR 91
TC 2
Z9 2
U1 4
U2 28
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0022-0965
EI 1096-0457
J9 J EXP CHILD PSYCHOL
JI J. Exp. Child Psychol.
PD NOV
PY 2014
VL 127
SI SI
BP 144
EP 162
DI 10.1016/j.jecp.2014.01.008
PG 19
WC Psychology, Developmental; Psychology, Experimental
SC Psychology
GA AO7SZ
UT WOS:000341554200011
PM 24630759
ER
PT J
AU Lopez, T
Pumarega, JA
Pollack, AZ
Lee, DH
Richiardi, L
Jacobs, DR
Schisterman, EF
Porta, M
AF Lopez, Tomas
Pumarega, Jose A.
Pollack, Anna Z.
Lee, Duk-Hee
Richiardi, Lorenzo
Jacobs, David R., Jr.
Schisterman, Enrique F.
Porta, Miguel
TI Adjusting serum concentrations of organochlorine compounds by lipids and
symptoms: A causal framework for the association with K-ras mutations in
pancreatic cancer
SO CHEMOSPHERE
LA English
DT Article
DE Causal directed acyclic graph (DAG); Pancreatic neoplasm; Organochlorine
compounds; Lipids; K-ras gene; Disease progression
ID PERSISTENT ORGANIC POLLUTANTS; HUMAN HEALTH-RISKS; ENVIRONMENTAL
CONTAMINANTS; GENERAL-POPULATION; BLOOD-EXTRACTION; EPIDEMIOLOGY;
ADJUSTMENT; LYMPHOMA; EXPOSURE; PCBS
AB In clinically aggressive diseases, patients experience pathophysiological changes that often alter concentrations of lipids and environmental lipophilic factors; such changes are related to disease signs and symptoms. The aim of the study was to compare the effects of correcting for total serum lipids (TSL) and other clinical factors on the odds of mutations in the K-ras oncogene by organochlorine compounds (OCs), in logistic models, in 103 patients with exocrine pancreatic cancer (EPC) using a causal directed acyclic graph (DAG) framework. Results and likelihood of bias were discussed in the light of possible causal scenarios. The odds of K-ras mutated EPC was associated with some TSL-corrected OCs, including p,p'-DDT (p-value: 0.008) and polychlorinated biphenyl 138 (p-trend: 0.024). When OCs were not corrected by TSL, the OR of a K-ras mutation was significant for p,p'-DDT (p-trend: 0.035). Additionally adjusting for cholestatic syndrome increased the ORs of TSL-corrected OCs. When models were adjusted by the interval from first symptom to blood extraction (ISE), the ORs increased for both TSL-corrected and uncorrected OCs. Models with TSL-corrected OCs and adjusted for cholestatic syndrome or ISE yielded the highest ORs. We show that DAGs clarify the covariates necessary to minimize bias, and demonstrate scenarios under which adjustment for TSL-corrected OCs and failure to adjust for symptoms or ISE may induce bias. Models with TSL-uncorrected OCs may be biased too, and adjusting by symptoms or ISE may not control such biases. Our findings may have implications as well for studying environmental causes of other clinically aggressive diseases. (C) 2014 Elsevier Ltd. All rights reserved.
C1 [Lopez, Tomas; Pumarega, Jose A.; Porta, Miguel] Hosp Mar Med Res Inst IMIM, Barcelona, Spain.
[Lopez, Tomas; Porta, Miguel] Univ Autonoma Barcelona, Fac Med, Catalonia, Spain.
[Pumarega, Jose A.; Porta, Miguel] CIBERESP, Madrid, Spain.
[Pollack, Anna Z.; Schisterman, Enrique F.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Rockville, MD USA.
[Lee, Duk-Hee] Kyungpook Natl Univ, Hlth Promot Res Ctr, Sch Med, Taegu, South Korea.
[Lee, Duk-Hee] Kyungpook Natl Univ, Dept Prevent Med, Taegu, South Korea.
[Richiardi, Lorenzo] Univ Turin & CPO Piemonte, Dept Med Sci, Canc Epidemiol Unit, Turin, Italy.
[Jacobs, David R., Jr.] Univ Minnesota, Sch Publ Hlth, Div Epidemiol, Minneapolis, MN USA.
RP Porta, M (reprint author), IMIM PRBB UAB, Carrer Dr Aiguader 88, E-08003 Barcelona, Spain.
EM mporta@imim.es
RI Porta, Miquel/B-5787-2008;
OI Porta, Miquel/0000-0003-1684-7428; Lopez-Jimenez,
Tomas/0000-0001-8255-4936; richiardi, lorenzo/0000-0003-0316-9402;
Pollack, Anna/0000-0002-4313-3298; Schisterman,
Enrique/0000-0003-3757-641X
NR 33
TC 0
Z9 0
U1 2
U2 25
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 NOV
PY 2014
VL 114
BP 219
EP 225
DI 10.1016/j.chemosphere.2014.04.066
PG 7
WC Environmental Sciences
SC Environmental Sciences & Ecology
GA AO0HX
UT WOS:000340990800029
PM 25113205
ER
PT J
AU Reddy, SY
Rasmussen, NA
Fourie, NH
Berger, RS
Martino, AC
Gill, J
Longchamps, R
Wang, XM
Heitkemper, MM
Henderson, WA
AF Reddy, Swarnalatha Y.
Rasmussen, Nat A.
Fourie, Nicolaas H.
Berger, Rebecca S.
Martino, Angela C.
Gill, Jessica
Longchamps, Ryan
Wang, Xiao Min
Heitkemper, Margaret M.
Henderson, Wendy A.
TI Sleep quality, BDNF genotype and gene expression in individuals with
chronic abdominal pain
SO BMC MEDICAL GENOMICS
LA English
DT Article
DE Sleep; Gene expression; BDNF; Chronic abdominal pain
ID IRRITABLE-BOWEL-SYNDROME; GROWTH-FACTOR-I; VAL66MET POLYMORPHISM; APNEA
SYNDROME; DISEASE; DISORDERS; ADULTS; PREVALENCE; SYMPTOMS; HORMONE
AB Background: Sleep quality and genetics may contribute to the etiology of gastrointestinal (GI) symptoms. Individuals with impaired sleep often have a number of associated symptoms including chronic abdominal pain (CAP). The current study examined the interactions of brain-derived neurotrophic factor (BDNF) genotype with sleep quality in persons with CAP and healthy controls. In addition, associations among sleep quality, BDNF genotype, and gene expression were explored in the participants.
Methods: Data were collected on 59 participants (46% male, 61% White, 26.9 +/- 6.6 years; CAP (n= 19) and healthy controls (n= 40)). Participants with CAP reported poorer sleep quality compared to healthy controls. BDNF genotype, categorized as Val/Val homozygotes versus the Met carriers.
Results: Microarray analysis found twenty-four differentially expressed genes by a two-fold magnitude in participants with poor sleep quality compared to good sleep quality, and seven differentially expressed genes comparing CAP to healthy control. Three specific genes in the pain group overlap with sleep quality, including insulin-like growth factor 1 (IGF1), spermatogenesis associated serine-rich 2-like (SPATS2L), and immunoglobulin heavy constant gamma 1 or mu (IGHG1/// IGHM). BDNF was shown to have an interaction effect with GI and sleep symptoms.
Conclusions: Participants with CAP reported poor sleep quality compared to healthy controls. The role of the BDNF Met allele on differential gene expression was not distinct as main factor, but impacted interactions with sleep quality and CAP. Down-regulation of IGF1, SPATS2L, and IGHG1 expression may be related to the etiology of poor sleep quality and CAP.
C1 [Reddy, Swarnalatha Y.; Rasmussen, Nat A.; Fourie, Nicolaas H.; Berger, Rebecca S.; Martino, Angela C.; Gill, Jessica; Longchamps, Ryan; Wang, Xiao Min; Henderson, Wendy A.] NINR, Div Intramural Res, NIH, Dept Hlth & Human Resources, Bethesda, MD 20892 USA.
[Heitkemper, Margaret M.] Univ Washington, Sch Nursing, Seattle, WA 98195 USA.
RP Henderson, WA (reprint author), NINR, Div Intramural Res, NIH, Dept Hlth & Human Resources, 10 Ctr Dr,Bldg 10,2-1341, Bethesda, MD 20892 USA.
EM hendersw@mail.nih.gov
RI Reddy, Swarna/G-5349-2013;
OI Henderson, Wendy/0000-0003-3924-7118
FU Clinical Trials Database at NIH; Intramural Research Program, National
Institute of Nursing Research [1ZIANR000018-01-04]; National Institutes
of Health, Department of Health and Human Services, Bethesda, Maryland,
United States of America
FX The protocol (09-NR-0064) was approved by the Institutional Review Board
at the National Institutes of Health. Clinicaltrial. gov # NCT00824941.
We acknowledge the support and maintenance of Clinical Trials Database
at NIH. Support was provided by the Intramural Research Program,
National Institute of Nursing Research (to W.A.H., 1ZIANR000018-01-04,
Summer Internship Program Awardee to R.S.B. and Intramural Research
Training Award to R.L. and N.H.F.), National Institutes of Health,
Department of Health and Human Services, Bethesda, Maryland, United
States of America. We thank the assistance received from Benjamin
Majors, Nayan Patel, Drs. R. Michael Peace, Arseima del Valle-Pinero,
Dan Wang and Hyung-Suk Kim. We appreciate the comments on the manuscript
from Drs. Joan K. Austin and Ann Cashion.
NR 42
TC 4
Z9 4
U1 0
U2 3
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1755-8794
J9 BMC MED GENOMICS
JI BMC Med. Genomics
PD OCT 31
PY 2014
VL 7
AR 61
DI 10.1186/s12920-014-0061-1
PG 12
WC Genetics & Heredity
SC Genetics & Heredity
GA AW2BR
UT WOS:000346093700001
PM 25358868
ER
PT J
AU Chen, PW
Luo, RB
Jian, XY
Randazzo, PA
AF Chen, Pei-Wen
Luo, Ruibai
Jian, Xiaoying
Randazzo, Paul A.
TI The Arf6 GTPase-activating Proteins ARAP2 and ACAP1 Define Distinct
Endosomal Compartments That Regulate Integrin alpha 5 beta 1 Traffic
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID CELL-MIGRATION; RECEPTOR TRAFFICKING; ACTIN CYTOSKELETON; SORTING
SIGNALS; COPI VESICLES; ADHESION; MEMBRANE; CLATHRIN; PHOSPHORYLATION;
ENDOCYTOSIS
AB Arf6 and the Arf6 GTPase-activating protein (GAP) ACAP1 are established regulators of integrin traffic important to cell adhesion and migration. However, the function of Arf6 with ACAP1 cannot explain the range of Arf6 effects on integrin-based structures. We propose that Arf6 has different functions determined, in part, by the associated Arf GAP. We tested this idea by comparing the Arf6 GAPs ARAP2 and ACAP1. We found that ARAP2 and ACAP1 had opposing effects on apparent integrin beta 1 internalization. ARAP2 knockdown slowed, whereas ACAP1 knockdown accelerated, integrin beta 1 internalization. Integrin beta 1 association with adaptor protein containing a pleckstrin homology (PH) domain, phosphotyrosine-binding (PTB) domain, and leucine zipper motif (APPL)-positive endosomes and EEA1-positive endosomes was affected by ARAP2 knockdown and depended on ARAP2 GAP activity. ARAP2 formed a complex with APPL1 and colocalized with Arf6 and APPL in a compartment distinct from the Arf6/ACAP1 tubular recycling endosome. In addition, although ACAP1 and ARAP2 each colocalized with Arf6, they did not colocalize with each other and had opposing effects on focal adhesions (FAs). ARAP2 overexpression promoted large FAs, but ACAP1 overexpression reduced FAs. Taken together, the data support a model in which Arf6 has at least two sites of opposing action defined by distinct Arf6 GAPs.
C1 [Chen, Pei-Wen; Luo, Ruibai; Jian, Xiaoying; Randazzo, Paul A.] NCI, Cellular & Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Randazzo, PA (reprint author), NCI, Cellular & Mol Biol Lab, Bldg 37,Rm 2012, Bethesda, MD 20892 USA.
EM randazzp@mail.nih.gov
RI Chen, Pei-Wen/B-7142-2015
FU NCI, National Institutes of Health [BC 007365]
FX This work was supported by the intramural program of the NCI, National
Institutes of Health (Project BC 007365).
NR 47
TC 9
Z9 9
U1 0
U2 10
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 OCT 31
PY 2014
VL 289
IS 44
BP 30237
EP 30248
DI 10.1074/jbc.M114.596155
PG 12
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA AS9FY
UT WOS:000344549700008
PM 25225293
ER
PT J
AU Gambhira, R
Keele, BF
Schell, JB
Hunter, MJ
Dufour, JP
Montefiori, DC
Tang, H
Rose, JK
Rose, N
Marx, PA
AF Gambhira, Ratish
Keele, Brandon F.
Schell, John B.
Hunter, Meredith J.
Dufour, Jason P.
Montefiori, David C.
Tang, Haili
Rose, John K.
Rose, Nina
Marx, Preston A.
TI Transmitted/Founder Simian Immunodeficiency Virus Envelope Sequences in
Vesicular Stomatitis and Semliki Forest Virus Vector Immunized Rhesus
Macaques
SO PLOS ONE
LA English
DT Article
ID GLYCOSYLATION SITES; BIOLOGICAL PHENOTYPE; GENETIC IDENTITY; PATHOGENIC
SIV; CHALLENGE; INFECTION; HIV; PROTECTION; VACCINE; TYPE-1
AB Identification of transmitted/founder simian immunodeficiency virus (SIV) envelope sequences responsible for infection may prove critical for understanding HIV/SIV mucosal transmission. We used single genome amplification and phylogenetic analyses to characterize transmitted/founder SIVs both in the inoculum and in immunized-infected rhesus monkeys. Single genome amplification of the SIVsmE660 inoculum revealed a maximum diversity of 1.4%. We also noted that the consensus sequence of the challenge stock differed from the vaccine construct in 10 amino acids including 3 changes in the V4 loop. Viral env was prepared from rhesus plasma in 3 groups of 6 immunized with vesicular stomatitis virus (VSV) vectors and boosted with Semliki forest virus (SFV) replicons expressing (a) SIVsmE660 gag-env (b) SIVsmE660 gag-env plus rhesus GM-CSF and (c) control influenza hemagglutinin protein. Macaques were immunized twice with VSV-vectors and once with SFV vector and challenged intrarectally with 4000 TCID50. Single genome amplification characterized the infections of 2 unprotected animals in the gag-env immunized group, both of which had reduced acute plasma viral loads that ended as transient infections indicating partial immune control. Four of 6 rhesus were infected in the gag-env + GM-CSF group which demonstrated that GM-CSF abrogated protection. All 6 animals from the control group were infected having high plasma viral loads. We obtained 246 full-length envelope sequences from SIVsmE660 infected macaques at the peak of infection and determined the number of transmitted/founder variants per animal. Our analysis found that 2 of 2 gag-env vaccinated but infected macaques exhibited single but distinct virus envelope lineages whereas rhesus vaccinated with gag-env-GM-CSF or HA control exhibited both single and multiple env lineages. Because there were only 2 infected animals in the gagenv vaccinated rhesus compared to 10 infected rhesus in the other 2 groups, the significance of finding single env variants in the gag-env vaccinated group could not be established.
C1 [Gambhira, Ratish; Hunter, Meredith J.; Dufour, Jason P.; Marx, Preston A.] Tulane Univ, Tulane Natl Primate Res Ctr, Div Microbiol, Covington, LA 70433 USA.
[Keele, Brandon F.] SAIC Frederick Inc, Frederick Natl Lab Canc Res, AIDS & Canc Virus Program, Frederick, MD USA.
[Schell, John B.; Rose, John K.; Rose, Nina] Yale Univ, Dept Pathol, New Haven, CT USA.
[Montefiori, David C.; Tang, Haili] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA.
RP Marx, PA (reprint author), Tulane Univ, Tulane Natl Primate Res Ctr, Div Microbiol, Covington, LA 70433 USA.
EM pmarx@tulane.edu
FU National Cancer Institute, National Institutes of Health
[HHSN261200800001E]; NIH grant [AI45510]; National Center for Research
Resources; Office of Research Infrastructure Programs (ORIP) of the
National Institutes of Health [P51 RR00164]
FX This work was supported in part with federal funds from the National
Cancer Institute, National Institutes of Health under contract
HHSN261200800001E, NIH grant AI45510 and by the National Center for
Research Resources and the Office of Research Infrastructure Programs
(ORIP) of the National Institutes of Health through Grant Number P51
RR00164 to the Tulane National Primate Research Center. The funders had
no role in study design, data collection and analysis, decision to
publish, or preparation of the manuscript.
NR 39
TC 2
Z9 2
U1 0
U2 6
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD OCT 31
PY 2014
VL 9
IS 10
AR e109678
DI 10.1371/journal.pone.0109678
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AS0BN
UT WOS:000343943700014
PM 25360552
ER
PT J
AU Hamaneh, MB
Yu, YK
AF Hamaneh, Mehdi Bagheri
Yu, Yi-Kuo
TI Relating Diseases by Integrating Gene Associations and Information Flow
through Protein Interaction Network
SO PLOS ONE
LA English
DT Article
ID RECEPTOR-RELATED PROTEIN-5; MUTATIONS; IDENTIFICATION; DYSPLASIA;
ONTOLOGY; DATABASE; LRP5
AB Identifying similar diseases could potentially provide deeper understanding of their underlying causes, and may even hint at possible treatments. For this purpose, it is necessary to have a similarity measure that reflects the underpinning molecular interactions and biological pathways. We have thus devised a network-based measure that can partially fulfill this goal. Our method assigns weights to all proteins (and consequently their encoding genes) by using information flow from a disease to the protein interaction network and back. Similarity between two diseases is then defined as the cosine of the angle between their corresponding weight vectors. The proposed method also provides a way to suggest disease-pathway associations by using the weights assigned to the genes to perform enrichment analysis for each disease. By calculating pairwise similarities between 2534 diseases, we show that our disease similarity measure is strongly correlated with the probability of finding the diseases in the same disease family and, more importantly, sharing biological pathways. We have also compared our results to those of MimMiner, a text-mining method that assigns pairwise similarity scores to diseases. We find the results of the two methods to be complementary. It is also shown that clustering diseases based on their similarities and performing enrichment analysis for the cluster centers significantly increases the term association rate, suggesting that the cluster centers are better representatives for biological pathways than the diseases themselves. This lends support to the view that our similarity measure is a good indicator of relatedness of biological processes involved in causing the diseases. Although not needed for understanding this paper, the raw results are available for download for further study at ftp://ftp.ncbi.nlm.nih.gov/pub/qmbpmn/DiseaseRelations/.
C1 [Hamaneh, Mehdi Bagheri; Yu, Yi-Kuo] NIH, Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20892 USA.
RP Yu, YK (reprint author), NIH, Natl Lib Med, Natl Ctr Biotechnol Informat, Bldg 10, Bethesda, MD 20892 USA.
EM yyu@ncbi.nlm.nih.gov
FU National Library of Medicine at the National Institutes of Health
FX This work was supported by the Intramural Research Program of the
National Library of Medicine at the 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 41
TC 4
Z9 4
U1 0
U2 1
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD OCT 31
PY 2014
VL 9
IS 10
AR e110936
DI 10.1371/journal.pone.0110936
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AS0BN
UT WOS:000343943700053
PM 25360770
ER
PT J
AU Sekulic, V
Lawrence, JJ
Skinner, FK
AF Sekulic, Vladislav
Lawrence, J. Josh
Skinner, Frances K.
TI Using Multi-Compartment Ensemble Modeling As an Investigative Tool of
Spatially Distributed Biophysical Balances: Application to Hippocampal
Oriens-Lacunosum/Moleculare (O-LM) Cells
SO PLOS ONE
LA English
DT Article
ID GLOBUS-PALLIDUS NEURONS; CA1 PYRAMIDAL NEURONS; I-H; INHIBITORY
INTERNEURONS; CHANNEL EXPRESSION; THETA-RHYTHM; DENDRITES; NETWORK;
VARIABILITY; MODULATION
AB Multi-compartmental models of neurons provide insight into the complex, integrative properties of dendrites. Because it is not feasible to experimentally determine the exact density and kinetics of each channel type in every neuronal compartment, an essential goal in developing models is to help characterize these properties. To address biological variability inherent in a given neuronal type, there has been a shift away from using hand-tuned models towards using ensembles or populations of models. In collectively capturing a neuron's output, ensemble modeling approaches uncover important conductance balances that control neuronal dynamics. However, conductances are never entirely known for a given neuron class in terms of its types, densities, kinetics and distributions. Thus, any multi-compartment model will always be incomplete. In this work, our main goal is to use ensemble modeling as an investigative tool of a neuron's biophysical balances, where the cycling between experiment and model is a design criterion from the start. We consider orienslacunosum/moleculare (O-LM) interneurons, a prominent interneuron subtype that plays an essential gating role of information flow in hippocampus. O-LM cells express the hyperpolarization-activated current (I-h). Although dendritic I-h could have a major influence on the integrative properties of O-LM cells, the compartmental distribution of I-h on O-LM dendrites is not known. Using a high-performance computing cluster, we generated a database of models that included those with or without dendritic I-h. A range of conductance values for nine different conductance types were used, and different morphologies explored. Models were quantified and ranked based on minimal error compared to a dataset of OLM cell electrophysiological properties. Co-regulatory balances between conductances were revealed, two of which were dependent on the presence of dendritic I-h. These findings inform future experiments that differentiate between somatic and dendritic I-h, thereby continuing a cycle between model and experiment.
C1 [Sekulic, Vladislav; Skinner, Frances K.] Univ Hlth Network, Toronto Western Res Inst, Toronto, ON, Canada.
[Sekulic, Vladislav; Skinner, Frances K.] Univ Toronto, Dept Physiol, Toronto, ON, Canada.
[Skinner, Frances K.] Univ Toronto, Dept Med Neurol, Toronto, ON, Canada.
[Lawrence, J. Josh] Univ Montana, NIH, COBRE Ctr Struct & Funct Neurosci, Missoula, MT 59812 USA.
[Lawrence, J. Josh] Univ Montana, Dept Biomed & Pharmaceut Sci, Missoula, MT 59812 USA.
RP Sekulic, V (reprint author), Univ Hlth Network, Toronto Western Res Inst, Toronto, ON, Canada.
EM vlad.sekulic@utoronto.ca
FU National Institutes of Health; SciNet HPC Consortium; NIH [R01
NS069689]; NSERC [RGPIN203700-11]; University of Toronto Fellowship;
Natural Sciences and Engineering Research Council; Dept. of Physiology;
University of Toronto
FX This work was supported by National Institutes of Health, Natural
Sciences and Engineering Research Council, a Dept. of Physiology,
University of Toronto Fellowship, and the SciNet HPC Consortium. The
relevant grant numbers and websites for the funding agencies are: NIH
R01 NS069689 http://www.nih.gov; NSERC RGPIN203700-11
http://www.nserc-crsng.gc.ca/; University of Toronto Fellowship
http://www.physiology.utoronto.ca; SciNet HPC Consortium
http://www.scinethpc.ca/. The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 75
TC 2
Z9 2
U1 2
U2 7
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD OCT 31
PY 2014
VL 9
IS 10
AR e106567
DI 10.1371/journal.pone.0106567
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AS0BN
UT WOS:000343943700004
PM 25360752
ER
PT J
AU Sgobio, C
Kupferschmidt, DA
Cui, GH
Sun, LX
Li, Z
Cai, HB
Lovinger, DM
AF Sgobio, Carmelo
Kupferschmidt, David A.
Cui, Guohong
Sun, Lixin
Li, Zheng
Cai, Huaibin
Lovinger, David M.
TI Optogenetic Measurement of Presynaptic Calcium Transients Using
Conditional Genetically Encoded Calcium Indicator Expression in
Dopaminergic Neurons
SO PLOS ONE
LA English
DT Article
ID MUTANT ALPHA-SYNUCLEIN; KNOCK-OUT MICE; CHOLINERGIC INTERNEURONS;
PARKINSONS-DISEASE; NEUROTRANSMITTER RELEASE; STRIATAL SYNAPTOSOMES;
5-HT1B RECEPTORS; DORSAL STRIATUM; NEURAL ACTIVITY; TRANSMISSION
AB Calcium triggers dopamine release from presynaptic terminals of midbrain dopaminergic (mDA) neurons in the striatum. However, calcium transients within mDA axons and axon terminals are difficult to study and little is known about how they are regulated. Here we use a newly-developed method to measure presynaptic calcium transients (PreCaTs) in axons and terminals of mDA neurons with a genetically encoded calcium indicator (GECI) GCaMP3 expressed in transgenic mice. Using a photomultiplier tube-based system, we measured electrical stimulation-induced PreCaTs of mDA neurons in dorsolateral striatum slices from these mice. Single-pulse stimulation produced a transient increase in fluorescence that was completely blocked by a combination of N- and P/Q-type calcium channel blockers. DA and cholinergic, but not serotoninergic, signaling pathways modulated the PreCaTs in mDA fibers. These findings reveal heretofore unexplored dynamic modulation of presynaptic calcium in nigrostriatal terminals.
C1 [Sgobio, Carmelo; Sun, Lixin; Cai, Huaibin] NIA, Transgen Sect, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
[Kupferschmidt, David A.; Cui, Guohong; Lovinger, David M.] Natl Inst Alcohol Abuse & Alcoholism, Lab Integrat Neurosci, NIH, Rockville, MD USA.
[Li, Zheng] NIMH, Unit Synapse Dev & Plast, NIH, Bethesda, MD 20892 USA.
RP Cai, HB (reprint author), NIA, Transgen Sect, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
EM caih@mail.nih.gov; lovindav@mail.nih.gov
RI Li, Zheng/I-8016-2014
OI Li, Zheng/0000-0002-2978-2531
FU National Institute on Aging [Z01-000928, 000929]; Division of Intramural
Clinical and Biological Research of NIAAA [ZIA AA000407]
FX This study was supported in part by the intramural program of National
Institute on Aging (Z01-000928, 000929) and the Division of Intramural
Clinical and Biological Research of NIAAA (ZIA AA000407). The funders
had no role in study design, data collection and analysis, decision to
publish, or preparation of the manuscript.
NR 44
TC 3
Z9 3
U1 1
U2 13
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD OCT 31
PY 2014
VL 9
IS 10
AR e111749
DI 10.1371/journal.pone.0111749
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AS0BN
UT WOS:000343943700147
PM 25360513
ER
PT J
AU Waheed, AA
Kuruppu, ND
Felton, KL
D'Souza, D
Freed, EO
AF Waheed, Abdul A.
Kuruppu, Nishani D.
Felton, Kathryn L.
D'Souza, Darren
Freed, Eric O.
TI In COS Cells Vpu Can Both Stabilize Tetherin Expression and Counteract
Its Antiviral Activity
SO PLOS ONE
LA English
DT Article
ID VIRUS TYPE-1 VPU; HIV-1 VPU; PARTICLE RELEASE; INHIBITS HIV-1;
RETROVIRUS RELEASE; RESTRICTION FACTOR; MEMBRANE-PROTEIN;
DOWN-MODULATION; MECHANISM; SURFACE
AB The interferon-inducible cellular protein tetherin (CD317/BST-2) inhibits the release of a broad range of enveloped viruses. The HIV-1 accessory protein Vpu enhances virus particle release by counteracting this host restriction factor. While the antagonism of human tetherin by Vpu has been associated with both proteasomal and lysosomal degradation, the link between Vpu-mediated tetherin degradation and the ability of Vpu to counteract the antiviral activity of tetherin remains poorly understood. Here, we show that human tetherin is expressed at low levels in African green monkey kidney (COS) cells. However, Vpu markedly increases tetherin expression in this cell line, apparently by sequestering it in an internal compartment that bears lysosomal markers. This stabilization of tetherin by Vpu requires the transmembrane sequence of human tetherin. Although Vpu stabilizes human tetherin in COS cells, it still counteracts the ability of tetherin to suppress virus release. The enhancement of virus release by Vpu in COS cells is associated with a modest reduction in cell-surface tetherin expression, even though the overall expression of tetherin is higher in the presence of Vpu. This study demonstrates that COS cells provide a model system in which Vpu-mediated enhancement of HIV-1 release is uncoupled from Vpu-mediated tetherin degradation.
C1 [Waheed, Abdul A.; Kuruppu, Nishani D.; Felton, Kathryn L.; D'Souza, Darren; Freed, Eric O.] NCI, Virus Cell Interact Sect, HIV Drug Resistance Program, Frederick, MD 21701 USA.
RP Waheed, AA (reprint author), NCI, Virus Cell Interact Sect, HIV Drug Resistance Program, Frederick, MD 21701 USA.
EM waheedab@mail.nih.gov
FU Intramural Research Program of the NIH, National Cancer Institute;
Intramural AIDS targeted Antiviral Program
FX Research in the Freed lab is supported by the Intramural Research
Program of the NIH, National Cancer Institute, and by the Intramural
AIDS targeted Antiviral Program. The funders had no role in study
design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 71
TC 2
Z9 2
U1 0
U2 2
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD OCT 31
PY 2014
VL 9
IS 10
AR e111628
DI 10.1371/journal.pone.0111628
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AS0BN
UT WOS:000343943700131
PM 25360760
ER
PT J
AU Weng, PH
Huang, YL
Page, JH
Chen, JH
Xu, J
Koutros, S
Berndt, S
Chanock, S
Yeager, M
Witte, JS
Eeles, RA
Easton, DF
Neal, DE
Donovan, J
Hamdy, FC
Muir, KR
Giles, G
Severi, G
Smith, JR
Balistreri, CR
Shui, IM
Chen, YC
AF Weng, Pei-Hsuan
Huang, Yi-Ling
Page, John H.
Chen, Jen-Hau
Xu, Jianfeng
Koutros, Stella
Berndt, Sonja
Chanock, Stephen
Yeager, Meredith
Witte, John S.
Eeles, Rosalind A.
Easton, Douglas F.
Neal, David E.
Donovan, Jenny
Hamdy, Freddie C.
Muir, Kenneth R.
Giles, Graham
Severi, Gianluca
Smith, Jeffrey R.
Balistreri, Carmela R.
Shui, Irene M.
Chen, Yen-Ching
TI Polymorphisms of an Innate Immune Gene, Toll-Like Receptor 4, and
Aggressive Prostate Cancer Risk: A Systematic Review and Meta-Analysis
SO PLOS ONE
LA English
DT Review
ID GENOME-WIDE ASSOCIATION; SEQUENCE VARIANTS; TLR4 POLYMORPHISMS; OXIDIZED
LDL; SUSCEPTIBILITY; INFLAMMATION; ETIOLOGY; TOLL-LIKE-RECEPTOR-4;
PATHOPHYSIOLOGY; ADENOCARCINOMA
AB Background: Toll-like receptor 4 (TLR4) is one of the best known TLR members expressed on the surface of several leukocytes and tissue cells and has a key function in detecting pathogen and danger-associated molecular patterns. The role of TLR4 in the pathophysiology of several age-related diseases is also well recognized, such as prostate cancer (PCa). TLR4 polymorphisms have been related to PCa risk, but the relationship between TLR4 genotypes and aggressive PCa risk has not been evaluated by any systematic reviews.
Methods: We performed a systematic review and meta-analysis of candidate-gene and genome-wide association studies analyzing this relationship and included only white population. Considering appropriate criteria, only nine studies were analyzed in the meta-analysis, including 3,937 aggressive PCa and 7,382 controls.
Results: Using random effects model, no significant association was found in the ten TLR4 SNPs reported by at least four included studies under any inheritance model (rs2737191, rs1927914, rs10759932, rs1927911, rs11536879, rs2149356, rs4986790, rs11536889, rs7873784, and rs1554973). Pooled estimates from another ten TLR4 SNPs reported by three studies also showed no significant association (rs10759930, rs10116253, rs11536869, rs5030717, rs4986791, rs11536897, rs1927906, rs913930, rs1927905, and rs7045953). Meta-regression revealed that study type was not a significant source of between-study heterogeneity.
Conclusions: TLR4 polymorphisms were not significantly associated with the risk of aggressive PCa.
C1 [Weng, Pei-Hsuan] Taiwan Adventist Hosp, Dept Family Med, Taipei, Taiwan.
[Weng, Pei-Hsuan; Chen, Jen-Hau; Chen, Yen-Ching] Natl Taiwan Univ, Coll Publ Hlth, Inst Epidemiol & Prevent Med, Taipei 10764, Taiwan.
[Huang, Yi-Ling] Tufts Univ, Jean Mayer US Dept Agr Human Nutr Res Ctr Aging, Boston, MA 02111 USA.
[Page, John H.] Brigham & Womens Hosp, Dept Epidemiol, Channing Lab, Boston, MA 02115 USA.
[Chen, Jen-Hau] Natl Taiwan Univ Hosp, Dept Geriatr & Gerontol, Taipei, Taiwan.
[Xu, Jianfeng] Wake Forest Univ, Sch Med, Ctr Human Gen, Winston Salem, NC 27109 USA.
[Koutros, Stella; Berndt, Sonja; Chanock, Stephen] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Yeager, Meredith] NCI Frederick, SAIC Frederick Inc, Core Genotyping Fac, Frederick, MD USA.
[Yeager, Meredith] NCI, Div Canc Epidemiol & Genet, DHHS, NIH, Bethesda, MD 20892 USA.
[Witte, John S.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA.
[Witte, John S.] Univ Calif San Francisco, Ctr Human Genet, San Francisco, CA 94143 USA.
[Eeles, Rosalind A.] Inst Canc Res, Sutton, Surrey, England.
[Easton, Douglas F.] Univ Cambridge, Dept Publ Hlth & Primary Care, Ctr Canc Epidemiol, Strangeways Lab, Cambridge, England.
[Easton, Douglas F.] Univ Cambridge, Dept Oncol, Strangeways Lab, Cambridge, England.
[Neal, David E.] Univ Cambridge, Addenbrookes Hosp, Dept Oncol, Surg Oncol Uro Oncol S4, Cambridge CB2 2QQ, England.
[Neal, David E.] Univ Cambridge, Addenbrookes Hosp, Dept Surg, Cambridge CB2 2QQ, England.
[Donovan, Jenny] Univ Bristol, Dept Social Med, Bristol, Avon, England.
[Hamdy, Freddie C.] Univ Sheffield, Acad Urol Unit, Sheffield, S Yorkshire, England.
[Muir, Kenneth R.] Univ Nottingham, Sch Med, Queens Med Ctr, Nottingham, England.
[Giles, Graham; Severi, Gianluca] Canc Council Victoria, Canc Epidemiol Ctr, Melbourne, Vic, Australia.
[Smith, Jeffrey R.] Vanderbilt Univ, Sch Med, Dept Med, Nashville, TN 37212 USA.
[Balistreri, Carmela R.] Univ Palermo, Dept Pathobiol, Palermo, Italy.
[Shui, Irene M.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Chen, Yen-Ching] Natl Taiwan Univ, Coll Publ Hlth, Res Ctr Genes Environm & Human Hlth, Taipei 10764, Taiwan.
[Chen, Yen-Ching] Natl Taiwan Univ, Coll Publ Hlth, Dept Publ Hlth, Taipei 10764, Taiwan.
RP Chen, YC (reprint author), Natl Taiwan Univ, Coll Publ Hlth, Inst Epidemiol & Prevent Med, Taipei 10764, Taiwan.
EM karenchen@ntu.edu.tw
RI Balistreri, Carmela Rita/K-9495-2016; Chen, Yen-Ching/D-1098-2010;
OI Balistreri, Carmela Rita/0000-0002-5393-1007; Eeles,
Rosalind/0000-0002-3698-6241; Chen, Yen-Ching/0000-0002-8159-7202;
Giles, Graham/0000-0003-4946-9099
FU BLRD VA [I01 BX002502]
NR 55
TC 3
Z9 3
U1 0
U2 11
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD OCT 31
PY 2014
VL 9
IS 10
AR e110569
DI 10.1371/journal.pone.0110569
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AS0BN
UT WOS:000343943700038
PM 25360682
ER
PT J
AU Zhang, XY
Cowan, BR
Bluemke, DA
Finn, JP
Fonseca, CG
Kadish, AH
Lee, DC
Lima, JAC
Suinesiaputra, A
Young, AA
Medrano-Gracia, P
AF Zhang, Xingyu
Cowan, Brett R.
Bluemke, David A.
Finn, J. Paul
Fonseca, Carissa G.
Kadish, Alan H.
Lee, Daniel C.
Lima, Joao A. C.
Suinesiaputra, Avan
Young, Alistair A.
Medrano-Gracia, Pau
TI Atlas-Based Quantification of Cardiac Remodeling Due to Myocardial
Infarction
SO PLOS ONE
LA English
DT Article
ID LEFT-VENTRICULAR MASS; LOGISTIC-REGRESSION; MR-IMAGES; MODEL;
SEGMENTATION; BRAIN; CLASSIFICATION; HEART; SHAPE; IDENTIFICATION
AB Myocardial infarction leads to changes in the geometry (remodeling) of the left ventricle (LV) of the heart. The degree and type of remodeling provides important diagnostic information for the therapeutic management of ischemic heart disease. In this paper, we present a novel analysis framework for characterizing remodeling after myocardial infarction, using LV shape descriptors derived from atlas-based shape models. Cardiac magnetic resonance images from 300 patients with myocardial infarction and 1991 asymptomatic volunteers were obtained from the Cardiac Atlas Project. Finite element models were customized to the spatio-temporal shape and function of each case using guide-point modeling. Principal component analysis was applied to the shape models to derive modes of shape variation across all cases. A logistic regression analysis was performed to determine the modes of shape variation most associated with myocardial infarction. Goodness of fit results obtained from end-diastolic and end-systolic shapes were compared against the traditional clinical indices of remodeling: end-diastolic volume, end-systolic volume and LV mass. The combination of end-diastolic and end-systolic shape parameter analysis achieved the lowest deviance, Akaike information criterion and Bayesian information criterion, and the highest area under the receiver operating characteristic curve. Therefore, our framework quantitatively characterized remodeling features associated with myocardial infarction, better than current measures. These features enable quantification of the amount of remodeling, the progression of disease over time, and the effect of treatments designed to reverse remodeling effects.
C1 [Zhang, Xingyu; Cowan, Brett R.; Suinesiaputra, Avan; Young, Alistair A.; Medrano-Gracia, Pau] Univ Auckland, Dept Anat Radiol, Auckland 1, New Zealand.
[Bluemke, David A.] Natl Inst Biomed Imaging & Bioengn, Bethesda, MD USA.
[Finn, J. Paul; Fonseca, Carissa G.] Univ Calif Los Angeles, Dept Radiol, Los Angeles, CA USA.
[Kadish, Alan H.; Lee, Daniel C.] Northwestern Univ, Feinberg Sch Med, Feinberg Cardiovasc Res Inst, Chicago, IL 60611 USA.
[Lima, Joao A. C.] Johns Hopkins Univ, Donald W Reynolds Cardiovasc Clin Res Ctr, Baltimore, MD USA.
RP Medrano-Gracia, P (reprint author), Univ Auckland, Dept Anat Radiol, Auckland 1, New Zealand.
EM p.medrano@auckland.ac.nz
OI Bluemke, David/0000-0002-8323-8086
FU National Heart, Lung, and Blood Institute [R01HL087773, R01HL121754];
NHLBI [N01-HC-95159, N01-HC-95169]; NCRR [UL1-RR-024156, UL1-RR-025005];
St. Jude Medical, Inc; National Heart, Lung and Blood Institute
[R01HL91069]; NIH intramural research program; China Scholarship Council
FX This project was supported by award numbers R01HL087773 and R01HL121754
from the National Heart, Lung, and Blood Institute. The content is
solely the responsibility of the authors and does not necessarily
represent the official views of the National Heart, Lung, and Blood
Institute or the National Institutes of Health. MESA was supported by
contracts N01-HC-95159 through N01-HC-95169 from the NHLBI and by grants
UL1-RR-024156 and UL1-RR-025005 from NCRR. DETERMINE was supported by
St. Jude Medical, Inc; and the National Heart, Lung and Blood Institute
(R01HL91069). A list of participating DETERMINE investigators can be
found at http://www.clinicaltrials.gov. David A. Bluemke is supported by
the NIH intramural research program. Xingyu Zhang would like to
gratefully acknowledge financial support from the China Scholarship
Council. The funders had no role in study design, data collection and
analysis, decision to publish, or preparation of the manuscript.
NR 42
TC 12
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U1 0
U2 5
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD OCT 31
PY 2014
VL 9
IS 10
AR e110243
DI 10.1371/journal.pone.0110243
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AS0BN
UT WOS:000343943700028
PM 25360520
ER
PT J
AU Hepburn, L
Prajsnar, TK
Klapholz, C
Moreno, P
Loynes, CA
Ogryzko, NV
Brown, K
Schiebler, M
Hegyi, K
Antrobus, R
Hammond, KL
Connolly, J
Ochoa, B
Bryant, C
Otto, M
Surewaard, B
Seneviratne, SL
Grogono, DM
Cachat, J
Ny, T
Kaser, A
Torok, ME
Peacock, SJ
Holden, M
Blundell, T
Wang, LH
Ligoxygakis, P
Minichiello, L
Woods, CG
Foster, SJ
Renshaw, SA
Floto, RA
AF Hepburn, Lucy
Prajsnar, Tomasz K.
Klapholz, Catherine
Moreno, Pablo
Loynes, Catherine A.
Ogryzko, Nikolay V.
Brown, Karen
Schiebler, Mark
Hegyi, Krisztina
Antrobus, Robin
Hammond, Katherine L.
Connolly, John
Ochoa, Bernardo
Bryant, Clare
Otto, Michael
Surewaard, Bas
Seneviratne, Suranjith L.
Grogono, Dorothy M.
Cachat, Julien
Ny, Tor
Kaser, Arthur
Toeroek, M. Estee
Peacock, Sharon J.
Holden, Matthew
Blundell, Tom
Wang, Lihui
Ligoxygakis, Petros
Minichiello, Liliana
Woods, C. Geoff
Foster, Simon J.
Renshaw, Stephen A.
Floto, R. Andres
TI A Spaetzle-like role for nerve growth factor beta in vertebrate immunity
to Staphylococcus aureus
SO SCIENCE
LA English
DT Article
ID SIGNALING PATHWAY; INNATE IMMUNITY; HOST-DEFENSE; DROSOPHILA; TOLL;
INFECTIONS; ACTIVATION; MECHANISM; MUTATION; RELEASE
AB Many key components of innate immunity to infection are shared between Drosophila and humans. However, the fly Toll ligandSpaetzle is not thought to have a vertebrate equivalent. We have found that the structurally related cystine-knot protein, nerve growth factor beta (NGF beta), plays an unexpected Spaetzle-like role in immunity to Staphylococcus aureus infection in chordates. Deleterious mutations of either human NGF beta or its high-affinity receptor tropomyosin-related kinase receptor A (TRKA) were associated with severe S. aureus infections. NGF beta was released by macrophages in response to S. aureus exoproteins through activation of the NOD-like receptors NLRP3 and NLRP4 and enhanced phagocytosis and superoxide-dependent killing, stimulated proinflammatory cytokine production, and promoted calcium-dependent neutrophil recruitment. TrkA knockdown in zebrafish increased susceptibility to S. aureus infection, confirming an evolutionarily conserved role for NGF beta-TRKA signaling in pathogen-specific host immunity.
C1 [Hepburn, Lucy; Klapholz, Catherine; Moreno, Pablo; Brown, Karen; Schiebler, Mark; Hegyi, Krisztina; Antrobus, Robin; Woods, C. Geoff; Floto, R. Andres] Univ Cambridge, Cambridge Inst Med Res, Cambridge CB2 1TN, England.
[Hepburn, Lucy; Klapholz, Catherine; Brown, Karen; Schiebler, Mark; Hegyi, Krisztina; Grogono, Dorothy M.; Kaser, Arthur; Toeroek, M. Estee; Peacock, Sharon J.; Floto, R. Andres] Univ Cambridge, Dept Med, Cambridge CB2 1TN, England.
[Prajsnar, Tomasz K.; Connolly, John; Foster, Simon J.; Renshaw, Stephen A.] Univ Sheffield, Krebs Inst, Sheffield S10 2TN, S Yorkshire, England.
[Prajsnar, Tomasz K.; Connolly, John; Foster, Simon J.] Univ Sheffield, Dept Mol Biol & Biotechnol, Sheffield S10 2TN, S Yorkshire, England.
[Prajsnar, Tomasz K.; Loynes, Catherine A.; Ogryzko, Nikolay V.; Hammond, Katherine L.; Renshaw, Stephen A.] Univ Sheffield, Bateson Ctr, Sheffield S10 2TN, S Yorkshire, England.
[Loynes, Catherine A.; Hammond, Katherine L.; Renshaw, Stephen A.] Univ Sheffield, Dept Infect & Immun, Sheffield S10 2TN, S Yorkshire, England.
[Brown, Karen; Grogono, Dorothy M.; Floto, R. Andres] Papworth Hosp, Cambridge Ctr Lung Infect, Cambridge CB3 8RE, England.
[Ochoa, Bernardo; Blundell, Tom] Univ Cambridge, Dept Biochem, Cambridge CB2 1TN, England.
[Bryant, Clare] Univ Cambridge, Dept Vet Med, Cambridge CB2 1TN, England.
[Otto, Michael] NIAID, Lab Human Bacterial Pathogenesis, NIH, Bethesda, MD 20892 USA.
[Surewaard, Bas] Univ Med Ctr, Dept Med Microbiol, Utrecht, Netherlands.
[Seneviratne, Suranjith L.] Royal Free Hosp London, Dept Clin Immunol, London, England.
[Cachat, Julien] Univ Geneva, Dept Pathol & Immunol, CH-1211 Geneva 4, Switzerland.
[Ny, Tor] Umea Univ, Dept Med Biochem & Biophys, S-90187 Umea, Sweden.
[Peacock, Sharon J.; Holden, Matthew] Wellcome Trust Sanger Inst, Hinxton, England.
[Holden, Matthew] Univ St Andrews, Sch Med, St Andrews KY16 9AJ, Fife, Scotland.
[Wang, Lihui; Ligoxygakis, Petros] Univ Oxford, Biochem Dept, Oxford OX1 2JD, England.
[Minichiello, Liliana] Univ Oxford, Pharmacol Dept, Oxford OX1 2JD, England.
[Woods, C. Geoff] Univ Cambridge, Dept Med Genet, Cambridge CB2 1TN, England.
RP Renshaw, SA (reprint author), Univ Sheffield, Krebs Inst, Western Bank, Sheffield S10 2TN, S Yorkshire, England.
EM s.a.renshaw@sheffield.ac.uk; arf27@cam.ac.uk
RI Renshaw, Stephen/E-6192-2010;
OI Renshaw, Stephen/0000-0003-1790-1641; Connolly, John/0000-0002-9232-7929
FU Wellcome Trust [084953, 089981]; Wellcome Trust [Medical Research
Council, UK] [G0700091, G0701932]; Papworth Hospital; National Institute
for Health Research Cambridge Biomedical Research Centre; NIAID, NIH
FX We thank S. Clegg and E. Henderson for help with patient samples, R.
Mifsud and D. Cusens for initial phylogenetic and functional analysis,
A. Segal for provision of Nod2-/- mouse bone marrow, and the
aquarium staff of the Bateson Centre, University of Sheffield for
zebrafish husbandry. This work was supported by The Wellcome Trust
[Senior Clinical Research Fellowship to R. A. F. (084953), project grant
to S.J.F./S.A.R. (089981), The Medical Research Council, UK (Research
center grant (G0700091), Senior Clinical Fellowship to S.A.R.
(G0701932)], Papworth Hospital and the National Institute for Health
Research Cambridge Biomedical Research Centre, and the Intramural
Research Program of NIAID, NIH.
NR 30
TC 20
Z9 21
U1 1
U2 16
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 OCT 31
PY 2014
VL 346
IS 6209
SI SI
BP 641
EP 646
DI 10.1126/science.1258705
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AR8BE
UT WOS:000343799700052
PM 25359976
ER
PT J
AU Gan, CP
Patel, V
Mikelis, CM
Zain, RB
Molinolo, AA
Abraham, MT
Teo, SH
Rahman, ZAA
Gutkind, JS
Cheong, SC
AF Gan, Chai Phei
Patel, Vyomesh
Mikelis, Constantinos M.
Zain, Rosnah Binti
Molinolo, Alfredo A.
Abraham, Mannil Thomas
Teo, Soo-Hwang
Rahman, Zainal Ariff Abdul
Gutkind, J. Silvio
Cheong, Sok Ching
TI Heterotrimeric G-protein alpha-12 (G ' 12) subunit promotes oral cancer
metastasis
SO ONCOTARGET
LA English
DT Article
DE Oral squamous cell carcinoma; G-protein alpha-12; Lymph node; Metastasis
ID SQUAMOUS-CELL CARCINOMA; LYMPH-NODE INVOLVEMENT; COUPLED RECEPTORS;
MUTATIONAL LANDSCAPE; PLATELET ACTIVATION; G13 PROTEINS; G ALPHA(12);
IN-VITRO; MIGRATION; G-ALPHA-12
AB Oral squamous cell carcinoma (OSCC) has a propensity to spread to the cervical lymph nodes (LN). The presence of cervical LN metastases severely impacts patient survival, whereby the two-year survival for oral cancer patients with involved LN is similar to 30% compared to over 80% in patients with non-involved LN. Elucidation of key molecular mechanisms underlying OSCC metastasis may afford an opportunity to target specific genes, to prevent the spread of OSCC and to improve patient survival. In this study, we demonstrated that expression of the heterotrimeric G-protein alpha-12 (G'12) is highly up-regulated in primary tumors and LN of OSCC patients, as assessed by quantitative polymerase chain reaction (qPCR) and immunohistochemistry (IHC). We also found that exogenous expression of the constitutively activated-form of G'12 promoted cell migration and invasion in OSCC cell lines. Correspondingly, inhibition of G'12 expression by shRNA consistently inhibited OSCC cell migration and invasion in vitro. Further, the inhibition of G12 signaling by regulator of G-protein signaling (RGS) inhibited G'12-mediated RhoA activation, which in turn resulted in reduced LN metastases in a tongue-orthotopic xenograft mouse model of oral cancer. This study provides a rationale for future development and evaluation of drug candidates targeting G'12-related pathways for metastasis prevention.
C1 [Gan, Chai Phei; Patel, Vyomesh; Teo, Soo-Hwang; Cheong, Sok Ching] Canc Res Initiat Fdn CARIF, Oral Canc Res Team, Selangor, Malaysia.
[Patel, Vyomesh; Mikelis, Constantinos M.; Molinolo, Alfredo A.; Gutkind, J. Silvio] Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD USA.
[Zain, Rosnah Binti; Rahman, Zainal Ariff Abdul; Cheong, Sok Ching] Univ Malaya, Fac Dent, Dept Oromaxillofacial Surg & Med Sci, Kuala Lumpur, Malaysia.
[Zain, Rosnah Binti] Univ Malaya, OCRCC, Kuala Lumpur, Malaysia.
[Abraham, Mannil Thomas] Tengku Ampuan Rahimah Hosp, Dept Oral & Maxillofacial Surg, Klang, Malaysia.
RP Cheong, SC (reprint author), Canc Res Initiat Fdn CARIF, Oral Canc Res Team, Selangor, Malaysia.
EM sokching.cheong@carif.com.my
RI Teo, Soo-hwang/H-2353-2014; ABDUL RAHMAN, ZAINAL ARIFF/C-1120-2010;
Management Center, Dental Research/C-2478-2013
FU UICC (ICRETT); MOSTI [06-00-00-0000]; CARIF;
[UM.C/625/1/HIR/MOHE/DENT-03]
FX This study was funded by UICC (ICRETT), MOSTI (06-00-00-0000),
UM.C/625/1/HIR/MOHE/DENT-03 and other supporters of CARIF. CARIF is a
non-profit research organization. We are committed to an understanding
of cancer prevention, diagnosis and treatment through a fundamental
research program. The authors would like to thank Susan Hoe (Institute
for Medical Research, Malaysia) for technical assistance with the cell
sorter.
NR 51
TC 8
Z9 8
U1 1
U2 5
PU IMPACT JOURNALS LLC
PI ALBANY
PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA
SN 1949-2553
J9 ONCOTARGET
JI Oncotarget
PD OCT 30
PY 2014
VL 5
IS 20
BP 9626
EP 9640
PG 15
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA AZ2AH
UT WOS:000348036500009
PM 25275299
ER
PT J
AU Park, JW
Zhao, L
Webb, P
Cheng, SY
AF Park, Jeong Won
Zhao, Li
Webb, Paul
Cheng, Sheue-Yann
TI Src-dependent phosphorylation at Y406 on the thyroid hormone receptor
beta confers the tumor suppressor activity
SO ONCOTARGET
LA English
DT Article
DE cSrc signaling; phosphorylation of thyroid hormone receptor beta 1;
tumor suppressor; breast cancer cells; xenograft models
ID C-ERBA-BETA; FAMILY TYROSINE KINASES; LIGAND-BINDING DOMAIN; NUCLEAR
RECEPTOR; BREAST-CANCER; XENOGRAFT MODELS; GENE; TUMORIGENESIS;
HETEROZYGOSITY; ACTIVATION
AB Association studies suggest that the thyroid hormone receptor beta 1 (TR beta 1) could function as a tumor suppressor in cancer cells. However, the underlying molecular mechanisms remain to be elucidated. We explored how TR beta 1 acted as a tumor suppressor in breast cancer MDA cells. Proliferation and invasiveness were markedly inhibited in cells stably expressing TR beta 1 (MDA-TR beta 1 cells). cSrc-phosphorylated TR beta 1 at Y406 signaled T3-induced degradation. Mutation of Y406 to Phe (TR beta 1Y406F) did not affect T3 binding affinity, but blocked T3-induced degradation in cells. Importantly, cell-based studies showed that TR beta 1Y406F lost the inhibitory effects by TR beta 1 on cell proliferation and invasion. Consistently, in xenograft models, MDA-TR beta 1 cells exhibited significantly slower tumor growth rates than those of Neo control cells. In contrast, the tumor growth rates of MDA-TR beta 1Y406F cells were indistinguishable from those of Neo control cells. We further showed that markedly more TR beta 1Y406F than TR beta 1 was physically associated with cSrc in cells, leading to constitutive activation of cSrc-FAK-ERK signaling. In contrast, degradation of T3-bound TR beta 1 complexed with cSrc attenuated signaling to decrease cell proliferation and invasiveness, thus confirming TR beta 1 as a tumor suppressor. Thus, the present studies suggested that TR beta 1 could be tested as a novel potential therapeutic target.
C1 [Park, Jeong Won; Zhao, Li; Cheng, Sheue-Yann] NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Webb, Paul] Houston Methodist Res Inst, Houston, TX USA.
RP Cheng, SY (reprint author), NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM chengs@mail.nih.gov
FU Intramural Research Program of the Center for Cancer Research, National
Cancer Institute, National Institutes of Health
FX This research was supported by the Intramural Research Program of the
Center for Cancer Research, National Cancer Institute, National
Institutes of Health.
NR 49
TC 4
Z9 6
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 OCT 30
PY 2014
VL 5
IS 20
BP 10002
EP 10016
PG 15
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA AZ2AH
UT WOS:000348036500038
PM 25275301
ER
PT J
AU Townsley, DM
Dumitriu, B
Young, NS
AF Townsley, Danielle M.
Dumitriu, Bogdan
Young, Neal S.
TI Bone marrow failure and the telomeropathies
SO BLOOD
LA English
DT Review
ID DOMINANT DYSKERATOSIS-CONGENITA; ACQUIRED APLASTIC-ANEMIA; HEMATOPOIETIC
STEM-CELLS; TELOMERE LENGTH; HUMAN FIBROBLASTS; CHROMOSOMAL INSTABILITY;
REPLICATIVE SENESCENCE; PULMONARY-FIBROSIS; OXIDATIVE STRESS; TERT LOCUS
AB Our understanding of the pathophysiology of aplastic anemia is undergoing significant revision, with implications for diagnosis and treatment. Constitutional and acquired disease is poorly delineated, as lesions in some genetic pathways cause stereotypical childhood syndromes and also act as risk factors for clinical manifestations in adult life. Telomere diseases are a prominent example of this relationship. Accelerated telomere attrition is the result of mutations in telomere repair genes and genes encoding components of the shelterin complex and related proteins. Genotype-phenotype correlations show genes responsible for X-linked (DKC1) and severe recessive childhood dyskeratosis congenita, typically with associated mucocutaneous features, and others (TERC and TERT) for more subtle presentation as telomeropathy in adults, in which multiorgan failure may be prominent. Telomerase mutations also are etiologic in familial pulmonary fibrosis and cryptic liver disease. Detection of a telomere disease requires awareness in the clinic, appropriate laboratory testing of telomere content, and genetic sequencing. In treatment decisions, genetic screening of related donors for hematopoietic stem cell transplantation is critical, and androgen therapy may be helpful. Telomeres shorten normally with aging, as well as under environmental circumstances, with regenerative stress and oxidative damage. Telomere biology is complexly related to oncogenesis: telomere attrition is protective by enforcing senescence or apoptosis in cells with a long mitotic history, but telomere loss also can destabilize the genome by chromosome rearrangement and aneuploidy.
C1 [Townsley, Danielle M.; Dumitriu, Bogdan; Young, Neal S.] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA.
RP Townsley, DM (reprint author), NHLBI, NIH, 10 Ctr Dr,CRC 3-5216, Bethesda, MD 20892 USA.
EM townsleydm@nhlbi.nih.gov
NR 107
TC 43
Z9 43
U1 2
U2 15
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA
SN 0006-4971
EI 1528-0020
J9 BLOOD
JI Blood
PD OCT 30
PY 2014
VL 124
IS 18
BP 2775
EP 2783
DI 10.1182/blood-2014-05-526285
PG 9
WC Hematology
SC Hematology
GA AY3BC
UT WOS:000347458500009
PM 25237198
ER
PT J
AU Scheinberg, P
Townsley, D
Dumitriu, B
Scheinberg, P
Weinstein, B
Daphtary, M
Rios, O
Wu, CO
Young, NS
AF Scheinberg, Phillip
Townsley, Danielle
Dumitriu, Bogdan
Scheinberg, Priscila
Weinstein, Barbara
Daphtary, Maithili
Rios, Olga
Wu, Colin O.
Young, Neal S.
TI Moderate-dose cyclophosphamide for severe aplastic anemia has
significant toxicity and does not prevent relapse and clonal evolution
SO BLOOD
LA English
DT Article
ID ANTITHYMOCYTE GLOBULIN; IMMUNOSUPPRESSIVE THERAPY; RANDOMIZED-TRIAL;
FOLLOW-UP; CYCLOSPORINE; TRANSPLANTATION; VORICONAZOLE; INFECTION; HORSE
AB First-line therapy of severe aplastic anemia (SAA) with high-dose cyclophosphamide causes toxicity and increased short-term mortality. We investigated cyclophosphamide at a lower, more moderate dose in combination with aggressive supportive care to determine whether severe infections might be avoided and hematologic outcomes defined for this regimen. From 2010 to 2012, 22 patients received cyclophosphamide at 120 mg/kg plus cyclosporine and antibacterial, antiviral, and antifungal prophylaxis. Toxicity was considerable, mainly due to prolonged absolute neutropenia, which occurred regardless of pretherapy blood counts, and persisted an average of 2 months. Granulocyte transfusions for uncontrolled infection were required in 5 patients, confirmed fungal infections were documented in 6, and 9 patients died. Nine patients (41%) responded at 6 months. After a median follow-up of 2.2 years, relapse occurred in 2 patients, and cytogenetic abnormalities (including monosomy 7) were observed in 4 patients. Although cyclophosphamide has activity in SAA, its toxicity is not justified when far less dangerous alternatives are available. This trial was registered at www.clinicaltrials.gov as #NCT01193283.
C1 [Scheinberg, Phillip; Townsley, Danielle; Dumitriu, Bogdan; Scheinberg, Priscila; Weinstein, Barbara; Daphtary, Maithili; Rios, Olga; Young, Neal S.] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA.
[Scheinberg, Phillip] Hosp Sao Jose, Antonio Ermirio de Moraes Canc Ctr, BR-01321001 Sao Paulo, Brazil.
[Scheinberg, Phillip] Beneficencia Portuguesa, Sao Paulo, Brazil.
[Wu, Colin O.] NHLBI, Off Biostat Res, NIH, Bethesda, MD 20892 USA.
RP Scheinberg, P (reprint author), Hosp Sao Jose, Rua Martiniano de Carvalho 951, BR-01321001 Sao Paulo, Brazil.
EM scheinbp@gmail.com
FU Intramural Research Program of the 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.
NR 23
TC 8
Z9 9
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 OCT 30
PY 2014
VL 124
IS 18
BP 2820
EP 2823
DI 10.1182/blood-2014-05-573642
PG 4
WC Hematology
SC Hematology
GA AY3BC
UT WOS:000347458500014
PM 25185712
ER
PT J
AU Chakraborty, PK
Schmitz-Abe, K
Kennedy, EK
Mamady, H
Naas, T
Durie, D
Campagna, DR
Lau, A
Sendamarai, AK
Wiseman, DH
May, A
Jolles, S
Connor, P
Powell, C
Heeney, MM
Giardina, PJ
Klaassen, RJ
Kannengiesser, C
Thuret, I
Thompson, AA
Marques, L
Hughes, S
Bonney, DK
Bottomley, SS
Wynn, RF
Laxer, RM
Minniti, CP
Moppett, J
Bordon, V
Geraghty, M
Joyce, PBM
Markianos, K
Rudner, AD
Holcik, M
Fleming, MD
AF Chakraborty, Pranesh K.
Schmitz-Abe, Klaus
Kennedy, Erin K.
Mamady, Hapsatou
Naas, Turaya
Durie, Danielle
Campagna, Dean R.
Lau, Ashley
Sendamarai, Anoop K.
Wiseman, Daniel H.
May, Alison
Jolles, Stephen
Connor, Philip
Powell, Colin
Heeney, Matthew M.
Giardina, Patricia-Jane
Klaassen, Robert J.
Kannengiesser, Caroline
Thuret, Isabelle
Thompson, Alexis A.
Marques, Laura
Hughes, Stephen
Bonney, Denise K.
Bottomley, Sylvia S.
Wynn, Robert F.
Laxer, Ronald M.
Minniti, Caterina P.
Moppett, John
Bordon, Victoria
Geraghty, Michael
Joyce, Paul B. M.
Markianos, Kyriacos
Rudner, Adam D.
Holcik, Martin
Fleming, Mark D.
TI Mutations in TRNT1 cause congenital sideroblastic anemia with
immunodeficiency, fevers, and developmental delay (SIFD)
SO BLOOD
LA English
DT Article
ID TRANSFER-RNA NUCLEOTIDYLTRANSFERASE; CCA ADDITION;
SACCHAROMYCES-CEREVISIAE
AB Mutations in genes encoding proteins that are involved in mitochondrial heme synthesis, iron-sulfur cluster biogenesis, and mitochondrial protein synthesis have previously been implicated in the pathogenesis of the congenital sideroblastic anemias (CSAs). We recently described a syndromic form of CSA associated with B-cell immunodeficiency, periodic fevers, and developmental delay (SIFD). Here we demonstrate that SIFD is caused by biallelic mutations in TRNT1, the gene encoding the CCA-adding enzyme essential for maturation of both nuclear and mitochondrial transfer RNAs. Using budding yeast lacking the TRNT1 homolog, CCA1, we confirm that the patient-associated TRNT1 mutations result in partial loss of function of TRNT1 and lead to metabolic defects in both the mitochondria and cytosol, which can account for the phenotypic pleiotropy.
C1 [Chakraborty, Pranesh K.; Mamady, Hapsatou; Naas, Turaya; Durie, Danielle] Univ Ottawa, Dept Pediat, Newborn Screening Ontario, Childrens Hosp Eastern Ontario, Ottawa, ON K1N 6N5, Canada.
[Schmitz-Abe, Klaus; Markianos, Kyriacos] Boston Childrens Hosp, Div Genet & Genom, Dept Med, Boston, MA USA.
[Kennedy, Erin K.; Rudner, Adam D.] Univ Ottawa, Ottawa Inst Syst Biol, Ottawa, ON, Canada.
[Kennedy, Erin K.; Rudner, Adam D.] Univ Ottawa, BMI, Ottawa, ON, Canada.
[Campagna, Dean R.; Lau, Ashley; Sendamarai, Anoop K.; Fleming, Mark D.] Boston Childrens Hosp, Dept Pathol, Boston, MA USA.
[Wiseman, Daniel H.; Bonney, Denise K.; Wynn, Robert F.] Royal Manchester Childrens Hosp, Dept Haematol, Manchester M27 1HA, Lancs, England.
[May, Alison] Cardiff Univ, Dept Haematol, Sch Med, Cardiff CF10 3AX, S Glam, Wales.
[Jolles, Stephen] Univ Wales Hosp, Immunodeficiency Ctr Wales, Cardiff CF4 4XW, S Glam, Wales.
[Connor, Philip] Childrens Hosp Wales, Dept Paediat, Cardiff, S Glam, Wales.
[Powell, Colin] Cardiff Univ, Inst Mol & Expt Med, Childrens Hosp Wales, Dept Child Hlth,Sch Med, Cardiff CF10 3AX, S Glam, Wales.
[Heeney, Matthew M.] Dana Farber Boston Childrens Canc & Blood Disorde, Boston, MA USA.
[Giardina, Patricia-Jane] Weill Cornell Med Coll, Div Hematol Oncol, Childrens Canc & Blood Fdn Labs, New York, NY USA.
[Klaassen, Robert J.; Geraghty, Michael] Univ Ottawa, Dept Pediat, Childrens Hosp Eastern Ontario, Ottawa, ON K1N 6N5, Canada.
[Kannengiesser, Caroline] Univ Paris Diderot, Hop Xavier Bichat, Assistance Publ Hosp Paris, INSERM UMR773,Dept Genet, Paris, France.
[Thuret, Isabelle] Hop Enfants La Timone, Dept Pediat Hematol, Marseille, France.
[Thompson, Alexis A.] Northwestern Univ, Dept Pediat, Feinberg Sch Med, Ann & Robert H Lurie Childrens Hosp, Chicago, IL 60611 USA.
[Marques, Laura] Ctr Hosp Porto, Dept Paediat, Infect Dis & Immunodeficiencies Unit, Oporto, Portugal.
[Hughes, Stephen] Royal Manchester Childrens Hosp, Dept Immunol, Manchester M27 1HA, Lancs, England.
[Bottomley, Sylvia S.] Univ Oklahoma, Coll Med, Dept Med, Hematol Oncol Sect, Oklahoma City, OK 73190 USA.
[Laxer, Ronald M.] Univ Toronto, Dept Paediat & Med, Hosp Sick Children, Toronto, ON M5S 1A1, Canada.
[Minniti, Caterina P.] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA.
[Moppett, John] Bristol Childrens Hosp, Bristol, Avon, England.
[Bordon, Victoria] Univ Ziekenhuis Ghent, Dept Pediat Hematooncol & Stem Cells Transplant, Ghent, Belgium.
[Joyce, Paul B. M.] Concordia Univ, Dept Chem & Biochem, Montreal, PQ H3G 1M8, Canada.
[Joyce, Paul B. M.] Concordia Univ, Ctr Struct & Funct Genom, Montreal, PQ H3G 1M8, Canada.
[Holcik, Martin] Univ Ottawa, Dept Pediat, Childrens Hosp Eastern Ontario, Mol Biomed Program,Res Inst, Ottawa, ON K1N 6N5, Canada.
RP Chakraborty, PK (reprint author), Childrens Hosp Eastern Ontario, Newborn Screening Ontario, Dept Pediat, 401 Smyth Rd, Ottawa, ON K1H 8L1, Canada.
EM pchakraborty@cheo.on.ca; mark.fleming@childrens.harvard.edu
RI Heeney, Matthew/J-6838-2015;
OI Wiseman, Daniel/0000-0003-0715-1402; Heeney,
Matthew/0000-0002-1104-6843; Wynn, robert/0000-0002-6046-8428; Jolles,
Stephen/0000-0002-7394-6804
FU Canadian Institutes of Health Research (CIHR); Natural Sciences and
Engineering Research Council of Canada (NSERC); CIHR; NSERC; Cancer
Research Society; Academic Health Sciences Centre Innovation fund;
Ontario Ministry of Health and Long Term Care Fund; National Institutes
of Health [R01 DK087992]; National Institute for Social Care and Health
Research Fellowship; Llandough Haematology Development Fund
FX This work was supported by the Canadian Institutes of Health Research
(CIHR) and the Natural Sciences and Engineering Research Council of
Canada (NSERC) (A.D.R.); grants from CIHR, NSERC, and the Cancer
Research Society (M.H.); CIHR, the Academic Health Sciences Centre
Innovation fund, and the Ontario Ministry of Health and Long Term Care
Fund (P.K.C.); the National Institutes of Health (grant R01 DK087992)
(K.M.); a National Institute for Social Care and Health Research
Fellowship (S.J.); and the Llandough Haematology Development Fund
(A.M.).
NR 15
TC 33
Z9 36
U1 0
U2 8
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 OCT 30
PY 2014
VL 124
IS 18
BP 2867
EP 2871
DI 10.1182/blood-2014-08-591370
PG 5
WC Hematology
SC Hematology
GA AY3BC
UT WOS:000347458500019
PM 25193871
ER
PT J
AU Taha, AY
Chang, LS
Chen, M
Rapoport, SI
Ramadan, E
AF Taha, Ameer Y.
Chang, Lisa
Chen, Mei
Rapoport, Stanley I.
Ramadan, Epolia
TI D2-like receptor activation does not initiate a brain docosahexaenoic
acid signal in unanesthetized rats
SO BMC NEUROSCIENCE
LA English
DT Article
DE Dopamine; Quinpirole; Neurotransmission; Docosahexaenoic acid; Release;
Signaling; Metabolism; Intracellular calcium; Calcium-independent
phospholipase A(2) (iPLA(2)); Calcium-dependent phospholipase A(2)
(cPLA(2)); Arachidonic acid
ID ALPHA-LINOLENIC ACID; MEDIUM SPINY NEURONS; ARACHIDONIC-ACID;
PHOSPHOLIPASE A(2); MUSCARINIC RECEPTORS; SMOOTH-MUSCLE; ADULT RATS;
DOPAMINE; CELLS; CALCIUM
AB Background: The polyunsaturated fatty acid, docosahexaenoic acid (DHA), participates in neurotransmission involving activation of calcium-independent phospholipase A(2) (iPLA(2)), which is coupled to muscarinic, cholinergic and serotonergic neuroreceptors. Drug induced activation of iPLA(2) can be measured in vivo with quantitative autoradiography using C-14-DHA as a probe. The present study used this approach to address whether a DHA signal is produced following dompaminergic (D) 2-like receptor activation with quinpirole in rat brain. Unanesthetized rats were infused intravenously with C-14-DHA one minute after saline or quinpirole infusion, and serial blood samples were collected over a 20-minute period to obtain plasma. The animals were euthanized with sodium pentobarbital and their brains excised, coronally dissected and subjected to quantitative autoradiography to derive the regional incorporation coefficient, k*, a marker of DHA signaling. Plasma labeled and unlabeled unesterified DHA concentrations were measured.
Results: The incorporation coefficient (k*) for DHA did not differ significantly between quinpirole-treated and control rats in any of 81 identified brain regions. Plasma labeled DHA concentration over the 20-minute collection period (input function) and unlabeled unesterified DHA concentration did not differ significantly between the two groups.
Conclusion: These findings demonstrate that D2-like receptor initiated signaling does not involve DHA as a second messenger, and likely does not involve iPLA(2) activation.
C1 [Taha, Ameer Y.; Chang, Lisa; Chen, Mei; Rapoport, Stanley I.; Ramadan, Epolia] NIA, Brain Physiol & Metab Sect, Neurosci Lab, NIH, Bethesda, MD 20892 USA.
RP Taha, AY (reprint author), NIA, Brain Physiol & Metab Sect, Neurosci Lab, NIH, Bldg 9,Room 1S126, Bethesda, MD 20892 USA.
EM ameer.taha@gmail.com
FU NIA intramural research program
FX This study was funded by the NIA intramural research program.
NR 42
TC 0
Z9 0
U1 1
U2 3
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2202
J9 BMC NEUROSCI
JI BMC Neurosci.
PD OCT 30
PY 2014
VL 15
AR 113
DI 10.1186/1471-2202-15-113
PG 8
WC Neurosciences
SC Neurosciences & Neurology
GA AU9QT
UT WOS:000345930600001
PM 25359512
ER
PT J
AU Kim, HF
Ghazizadeh, A
Hikosaka, O
AF Kim, Hyoung F.
Ghazizadeh, Ali
Hikosaka, Okihide
TI Separate groups of dopamine neurons innervate caudate head and tail
encoding flexible and stable value memories
SO FRONTIERS IN NEUROANATOMY
LA English
DT Article
DE nigrostriatal pathway; dopamine neuron; substantia nigra pars compacta;
parallel circuit; object value learning; macaque monkey
ID BASAL GANGLIA CIRCUITRY; SUBSTANTIA-NIGRA; PARKINSONS-DISEASE;
DORSOLATERAL STRIATUM; FUNCTIONAL-PROPERTIES; PROJECTION NEURONS; PARS
RETICULATA; EYE-MOVEMENTS; MONKEY; NUCLEUS
AB Dopamine (DA) neurons are thought to be critical for reward value-based learning by modifying synaptic transmissions in the striatum.Yet, different regions of the striatum seem to guide different kinds of learning. Do DA neurons contribute to the regional differences of the striatum in learning? As a first step to answer this question, we examined whether the head and tail of the caudate nucleus of the monkey (Macaca mulatta) receive inputs from the same or different DA neurons. We chose these caudate regions because we previously showed that caudate head neurons learn values of visual objects quickly and flexibly, whereas caudate tail neurons learn object values slowly but retain them stably. Here we confirmed the functional difference by recording single neuronal activity while the monkey performed the flexible and stable value tasks, and then injected retrograde tracers in the functional domains of caudate head and tail. The projecting dopaminergic neurons were identified using tyrosine hydroxylase immunohistochemistry. We found that two groups of DA neurons in the substantia nigra pars compacta project largely separately to the caudate head and tail. These groups of DA neurons were mostly separated topographically: head-projecting neurons were located in the rostral-ventral-medial region, while tail-projecting neurons were located in the caudal-dorsal-lateral regions of the substantia nigra. Furthermore, they showed different morphological features: tail-projecting neurons were larger and less circular than head-projecting neurons. Our data raise the possibility that different groups of DA neurons selectively guide learning of flexible (short-term) and stable (long-term) memories of object values.
C1 [Kim, Hyoung F.; Ghazizadeh, Ali; Hikosaka, Okihide] NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA.
RP Kim, HF (reprint author), NEI, Sensorimotor Res Lab, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM hyoung.f.kim@gmail.com
FU Intramural Research Program at the National Institutes of Health -
National Eye Institute
FX We express special thanks to K. S. Saleem and M. K. Smith for technical
assistance and suggestions. We also thank M. Yasuda, I. Monosov, and F.
Bromberg-Martin for discussions and D. Parker, I. Bunea, G.Tansey, A.M.
Nichols, T. W. Ruffner, J. W. McClurkin, and A. V. Hays for technical
assistance. This research was supported by the Intramural Research
Program at the National Institutes of Health - National Eye Institute.
NR 43
TC 10
Z9 10
U1 3
U2 14
PU FRONTIERS RESEARCH FOUNDATION
PI LAUSANNE
PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND
SN 1662-5129
J9 FRONT NEUROANAT
JI Front. Neuroanat.
PD OCT 30
PY 2014
VL 8
AR 120
DI 10.3389/fnana.2014.00120
PG 12
WC Anatomy & Morphology; Neurosciences
SC Anatomy & Morphology; Neurosciences & Neurology
GA AS3BZ
UT WOS:000344152300001
PM 25400553
ER
PT J
AU Bhansali, P
Hanigan, CL
Perera, L
Casero, RA
Tillekeratne, LMV
AF Bhansali, Pravin
Hanigan, Christin L.
Perera, Lalith
Casero, Robert A., Jr.
Tillekeratne, L. M. Viranga
TI Synthesis and biological evaluation of largazole analogues with modified
surface recognition cap groups
SO EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
LA English
DT Article
DE Antitumor agents; Biological activity; Antiproliferation; Histone
deacetylase inhibitors; Molecular modeling
ID HISTONE DEACETYLASE INHIBITORS; ISOFORM SELECTIVITY; INTERNAL CAVITY;
POTENT; HDAC; DESIGN; DERIVATIVES; THERAPY; SHI-1/2
AB Several largazole analogues with modified surface recognition cap groups were synthesized and their HDAC inhibitory activities were determined. The C7-epimer 12 caused negligible inhibition of HDAC activity, failed to induce global histone 3 (H3) acetylation in the HCT116 colorectal cancer cell line and demonstrated minimal effect on growth. Although previous studies have shown some degree of tolerance of structural changes at C7 position of largazole, these data show the negative effect of conformational change accompanying change of configuration at this position. Similarly, analogue 16a with D-1-naphthylmethyl side chain at C2 too had negligible inhibition of HDAC activity, failed to induce global histone 3 (H3) acetylation in the HCT116 colorectal cancer cell line and demonstrated minimal effect on growth. In contrast, the L-allyl analogue 16b and the L-1-naphthylmethyl analogue 16c were potent HDAC inhibitors, showing robust induction of global H3 acetylation and significant effect on cell growth. The data suggest that even bulky substituents are tolerated at this position, provided the stereochemistry at C2 is retained. With bulky substituents, inversion of configuration at C2 results in loss of inhibitory activity. The activity profiles of 16b and 16c on Class I HDAC1 vs Class II HDAC6 are similar to those of largazole and, taken together with x-ray crystallography information of HDAC8-largazole complex, may suggest that the C2 position of largazole is not a suitable target for structural optimization to achieve isoform selectivity. The results of these studies may guide the synthesis of more potent and selective HDAC inhibitors. (C) 2014 Elsevier Masson SAS. All rights reserved.
C1 [Bhansali, Pravin; Tillekeratne, L. M. Viranga] Univ Toledo, Coll Pharm & Pharmaceut Sci, Dept Med & Biol Chem, Toledo, OH 43606 USA.
[Hanigan, Christin L.; Casero, Robert A., Jr.] Johns Hopkins Univ, Sch Med, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21231 USA.
[Perera, Lalith] NIEHS, Struct Biol Lab, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA.
RP Tillekeratne, LMV (reprint author), Univ Toledo, Coll Pharm & Pharmaceut Sci, Dept Med & Biol Chem, 2801 W Bancroft St, Toledo, OH 43606 USA.
EM ltillek@utnet.utoledo.edu
FU NIH [CA51085]; Intramural Research Program of the NIH-National Institute
of Environmental Health Sciences [Z01 ES125392]
FX This work was supported, in part, by the NIH grant CA51085 (to RAC) and
by the Intramural Research Program of the NIH-National Institute of
Environmental Health Sciences (Z01 ES125392) (to LP). The authors thank
Dr. Yong Wah Kim of the Department of Chemistry, University of Toledo
for assistance with NMR spectroscopy.
NR 55
TC 5
Z9 6
U1 0
U2 19
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 OCT 30
PY 2014
VL 86
BP 528
EP 541
DI 10.1016/j.ejmech.2014.09.009
PG 14
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA AR7TD
UT WOS:000343781800047
PM 25203782
ER
PT J
AU Shchekotikhin, AE
Glazunova, VA
Dezhenkova, LG
Luzikov, YN
Buyanov, VN
Treshalina, HM
Lesnaya, NA
Romanenko, VI
Kaluzhny, DN
Balzarini, J
Agama, K
Pommier, Y
Shtil, AA
Preobrazhenskaya, MN
AF Shchekotikhin, Andrey E.
Glazunova, Valeria A.
Dezhenkova, Lyubov G.
Luzikov, Yuri N.
Buyanov, Vladimir N.
Treshalina, Helena M.
Lesnaya, Nina A.
Romanenko, Vladimir I.
Kaluzhny, Dmitry N.
Balzarini, Jan
Agama, Keli
Pommier, Yves
Shtil, Alexander A.
Preobrazhenskaya, Maria N.
TI Synthesis and evaluation of new antitumor
3-aminomethyl-4,11-dihydroxynaphtho[2,3-f]indole-5,10-diones
SO EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
LA English
DT Article
DE Naphtho[2,3-f]indole-5,10-diones; DNA ligands; Topoisomerase 1/2
inhibitors; Circumvention of multidrug resistance; Antitumor activity
ID TOPOISOMERASE-I INHIBITORS; CELL-CYCLE ARREST; ANTHRAQUINONE
DERIVATIVES; DNA-DAMAGE; CANCER; RESISTANCE; INDUCTION; COMPLEXES;
APOPTOSIS; KINASE
AB A series of new 3-aminomethyl-4,11-dihydroxynaphtho[2,3-f]indole-5,10-diones 6-13 bearing the cyclic diamine in the position 3 of the indole ring was synthesized. The majority of new compounds demonstrated a superior cytotoxicity than doxorubicin against a panel of mammalian tumor cells with determinants of altered drug response, that is, Pgp expression or p53 inactivation. For naphtho[2,3-f] indole-5,10-diones 6-9 bearing 3-aminopyrrolidine in the side chains, the ability to bind double-stranded DNA and inhibit topoisomerases 1 and 2 mediated relaxation of supercoiled DNA were demonstrated. Only one isomer, (R)-4,11-dihydroxy-3-((pyrrolidin-3-ylamino)methyl)-1H-naphtho[2,3-f]indole-5,10-dione (7) induced the formation of specific DNA cleavage products similar to the known topoisomerase 1 inhibitors camptothecin and indenoisoquinoline MJ-III-65, suggesting a role of the structure of the side chain of 3-aminomethylnaphtho[2,3-f]indole-5,10-diones in interaction with the target. Compound 7 demonstrated an antitumor activity in mice with P388 leukemia transplants whereas its enantiomer 6 was inactive. Thus, 3-aminomethyl derivatives of 4,11-dihydroxynaphtho[2,3-f] indole-5,10-dione emerge as a new prospective chemotype for the search of antitumor agents. (C) 2014 Elsevier Masson SAS. All rights reserved.
C1 [Shchekotikhin, Andrey E.; Dezhenkova, Lyubov G.; Luzikov, Yuri N.; Preobrazhenskaya, Maria N.] Russian Acad Med Sci, Gause Inst New Antibiot, Moscow 119021, Russia.
[Shchekotikhin, Andrey E.; Buyanov, Vladimir N.] Mendeleyev Univ Chem Technol, Moscow 125190, Russia.
[Glazunova, Valeria A.; Treshalina, Helena M.; Lesnaya, Nina A.; Romanenko, Vladimir I.; Shtil, Alexander A.] Blokhin Canc Ctr, Moscow 115478, Russia.
[Glazunova, Valeria A.; Shtil, Alexander A.] Moscow Engn & Phys Inst, Moscow 115409, Russia.
[Kaluzhny, Dmitry N.] Russian Acad Sci, Engelhardt Inst Mol Biol, Moscow 119991, Russia.
[Balzarini, Jan] Katholieke Univ Leuven, Rega Inst Med Res, B-3000 Leuven, Belgium.
[Agama, Keli; Pommier, Yves] NCI, Dev Therapeut Branch, NIH, Bethesda, MD 20892 USA.
RP Shchekotikhin, AE (reprint author), Russian Acad Med Sci, Gause Inst New Antibiot, 11 B Pirogovskaya St, Moscow 119021, Russia.
EM shchekotikhin@mail.ru
RI Glazunova, Valeria/I-1027-2015; Treshalina, Helen/P-8797-2015; Kaluzhny,
Dmitry/G-7256-2014
OI Glazunova, Valeria/0000-0001-6601-7700; Treshalina,
Helen/0000-0002-3878-3958;
FU Center for Cancer Research, Intramural Program of the US National Cancer
Institute [Z01 BC006161]
FX The authors thank A. Korolev and N. Maliutina (Gause Institute of New
Antibiotics) for HRMS and HPLS analyses; S. Sitdikova and F. Donenko
(Blokhin Cancer Center) for assistance in animal testing, and L. van
Berckelaer (KU Leuven) for help in cell proliferation assays. Y. Pommier
and K. Agama are supported by the Center for Cancer Research, Intramural
Program of the US National Cancer Institute (Z01 BC006161).
NR 49
TC 9
Z9 9
U1 0
U2 13
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 OCT 30
PY 2014
VL 86
BP 797
EP 805
DI 10.1016/j.ejmech.2014.09.021
PG 9
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA AR7TD
UT WOS:000343781800072
PM 25244612
ER
PT J
AU Barker, DJ
Herrera, C
West, MO
AF Barker, David J.
Herrera, Christopher
West, Mark O.
TI Automated detection of 50-kHz ultrasonic vocalizations using template
matching in XBAT
SO JOURNAL OF NEUROSCIENCE METHODS
LA English
DT Article
DE Affect; Ultrasonic vocalizations; Automatic detection; MATLAB;
Open-source
ID ADULT RATS; IDENTIFICATION; AMPHETAMINE; DOPAMINE
AB Background: Ultrasonic vocalizations (USVs) have been utilized to infer animals' affective states in multiple research paradigms including animal models of drug abuse, depression, fear or anxiety disorders, Parkinson's disease, and in studying neural substrates of reward processing. Currently, the analysis of USV data is performed manually, and thus is time consuming.
New method: The goal of the present study was to develop a method for automated USV recognition using a 'template detection' procedure for vocalizations in the 50-kHz range (35-80 kHz). The detector is designed to run within XBAT, a MATLAB graphical user interface and extensible bioacoustics tool developed at Cornell University.
Results: Results show that this method is capable of detecting >90% of emitted USVs and that time spent analyzing data by experimenters is greatly reduced.
Comparison with existing methods: Currently, no viable and publicly available methods exist for the automated detection of USVs. The present method, in combination with the XBAT environment is ideal for the USV community as it allows others to (1) detect USVs within a user-friendly environment, (2) make improvements to the detector and disseminate and (3) develop new tools for analysis within the MATLAB environment.
Conclusions: The present detector provides an open-source, accurate method for the detection of 50-kHz USVs. Ongoing research will extend the current method for use in the 22-kHz frequency range of ultrasonic vocalizations. Moreover, collaborative efforts among USV researchers may enhance the capabilities of the current detector via changes to the templates and the development of new programs for analysis. Published by Elsevier B.V.
C1 [Barker, David J.; Herrera, Christopher; West, Mark O.] Rutgers State Univ, Dept Psychol, Piscataway, NJ 08854 USA.
[Barker, David J.] Natl Inst Drug Abuse, Integrat Neurosci Res Branch, Neural Networks Sect, Baltimore, MD 21224 USA.
RP Barker, DJ (reprint author), Natl Inst Drug Abuse, Integrat Neurosci Res Branch, Neural Networks Sect, Baltimore, MD 21224 USA.
EM David.Barker@nih.gov
FU National Institute on Drug Abuse [DA006886, DA029873, DA032270]; Aresty
Center for Undergraduate Research
FX The authors thank Drs. Paul Clarke, Aaron Johnson, and Michelle Ciucci
as well as Laura Grant and Tina Scardochio for graciously providing data
to test the generalizability of the detector. Second, we would like to
thank Raimund Specht and the staff at Cornell's bioacoustic research
program for their continued assistance. Finally, we thank Steve Simmons,
Lisa Servilio, Danielle Bercovicz, Thomas Grace Sr., and Jackie Thomas,
for excellent assistance. This study was supported by the National
Institute on Drug Abuse Grants DA006886, DA029873 (MOW) and DA032270
(DJB) and the Aresty Center for Undergraduate Research (CH). The authors
have no financial interests to be disclosed. The funders had no role in
study design, data collection and analysis, decision to publish, or
preparation of the manuscript. All coauthors have seen and approve of
the contents of the manuscript.
NR 26
TC 2
Z9 2
U1 0
U2 4
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0165-0270
EI 1872-678X
J9 J NEUROSCI METH
JI J. Neurosci. Methods
PD OCT 30
PY 2014
VL 236
BP 68
EP 75
DI 10.1016/j.jneumeth.2014.08.007
PG 8
WC Biochemical Research Methods; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA AR2CH
UT WOS:000343390700009
PM 25128724
ER
PT J
AU Matlik, K
Abo-Ramadan, U
Harvey, BK
Arumae, U
Airavaara, M
AF Matlik, Kert
Abo-Ramadan, Usama
Harvey, Brandon K.
Arumae, Urmas
Airavaara, Mikko
TI AAV-mediated targeting of gene expression to the peri-infarct region in
rat cortical stroke model
SO JOURNAL OF NEUROSCIENCE METHODS
LA English
DT Article
DE Gene transfer; Focal ischemia; Animal models; Functional recovery;
Adeno-associated virus; Peri-infarct region
ID ADENOASSOCIATED VIRUS VECTORS; FOCAL CEREBRAL-ISCHEMIA; MIDBRAIN
DOPAMINE NEURONS; IN-VIVO; CDNF PROTECTS; MICE REVEALS; RECOVERY;
INCREASES; DELIVERY; INFARCTION
AB Background: For stroke patients the recovery of cognitive and behavioral functions is often incomplete. Functional recovery is thought to be mediated largely by connectivity rearrangements in the pen-infarct region. A method for manipulating gene expression in this region would be useful for identifying new recovery-enhancing treatments.
New method: We have characterized a way of targeting adeno-associated virus (AAV) vectors to the pen-infarct region of cortical ischemic lesion in rats 2 days after middle cerebral artery occlusion (MCAo). Results: We used magnetic resonance imaging (MRI) to show that the altered properties of post-ischemic brain tissue facilitate the spreading of intrastriatally injected nanoparticles toward the infarct. We show that subcortical injection of green fluorescent protein-encoding dsAAV7-GFP resulted in transduction of cells in and around the white matter tract underlying the lesion, and in the cortex proximal to the lesion. A similar result was achieved with dsAAV7 vector encoding the cerebral dopamine neurotrophic factor (CDNF), a protein with therapeutic potential.
Comparison with existing methods: Viral vector-mediated intracerebral gene delivery has been used before in rodent models of ischemic injury. However, the method of targeting gene expression to the pen-infarct region, after the initial phase of ischemic cell death, has not been described before.
Conclusions: We demonstrate a straightforward and robust way to target AAV vector-mediated overexpression of genes to the pen-infarct region in a rat stroke model. This method will be useful for studying the action of specific proteins in pen-infarct region during the recovery process. (C) 2014 Elsevier B.V. All rights reserved.
C1 [Matlik, Kert; Abo-Ramadan, Usama; Arumae, Urmas; Airavaara, Mikko] Univ Helsinki, Inst Biotechnol, FIN-00014 Helsinki, Finland.
[Harvey, Brandon K.] Natl Inst Drug Abuse, Intramural Res Program, Baltimore, MD 21224 USA.
[Arumae, Urmas] Tallinn Univ Technol, Dept Gene Technol, EE-12618 Tallinn, Estonia.
RP Airavaara, M (reprint author), Univ Helsinki, Inst Biotechnol, POB 56,Viikinkaari 9, FIN-00014 Helsinki, Finland.
EM mikko.airavaara@helsinki.fi
RI Arumae, Urmas/E-8290-2016;
OI Arumae, Urmas/0000-0003-3658-6464; Airavaara, Mikko/0000-0002-2026-1609
FU Sigrid Juselius Foundation; Biocentrum Helsinki; Academy of Finland
[250275, 256398]; European Union through the European Social Fund
(Mobilitas grant) [MTT84]; Finnish Graduate School of Neuroscience;
Georg and Ella Ehrnrooth Foundation; National Institute on Drug Abuse
National Institutes of Health, USA; Academy of Finlan [11186236]
FX The authors thank Doug Howard (NIDA IRP). We are also thankful to Kart
Varendi and Prof. Mart Saarma for their critical comments on the
manuscript. This study was financed from the Sigrid Juselius Foundation,
Biocentrum Helsinki, the Academy of Finland (grant number 250275 and
256398), the Academy of Finland Program 11186236 (Finnish Center of
Excellence Program 2008-2013), European Union through the European
Social Fund (Mobilitas grant MTT84), the Finnish Graduate School of
Neuroscience, the Georg and Ella Ehrnrooth Foundation and the Intramural
Research Program at the National Institute on Drug Abuse National
Institutes of Health, USA.
NR 31
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U1 0
U2 10
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0165-0270
EI 1872-678X
J9 J NEUROSCI METH
JI J. Neurosci. Methods
PD OCT 30
PY 2014
VL 236
BP 107
EP 113
DI 10.1016/j.jneumeth.2014.08.014
PG 7
WC Biochemical Research Methods; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA AR2CH
UT WOS:000343390700013
PM 25152446
ER
PT J
AU Ko, SY
Pegu, A
Rudicell, RS
Yang, ZY
Joyce, MG
Chen, XJ
Wang, KY
Bao, S
Kraemer, TD
Rath, T
Zeng, M
Schmidt, SD
Todd, JP
Penzak, SR
Saunders, KO
Nason, MC
Haase, AT
Rao, SS
Blumberg, RS
Mascola, JR
Nabel, GJ
AF Ko, Sung-Youl
Pegu, Amarendra
Rudicell, Rebecca S.
Yang, Zhi-yong
Joyce, M. Gordon
Chen, Xuejun
Wang, Keyun
Bao, Saran
Kraemer, Thomas D.
Rath, Timo
Zeng, Ming
Schmidt, Stephen D.
Todd, John-Paul
Penzak, Scott R.
Saunders, Kevin O.
Nason, Martha C.
Haase, Ashley T.
Rao, Srinivas S.
Blumberg, Richard S.
Mascola, John R.
Nabel, Gary J.
TI Enhanced neonatal Fc receptor function improves protection against
primate SHIV infection
SO NATURE
LA English
DT Article
ID NEUTRALIZING ANTIBODIES; HALF-LIFE; HIV-1 VACCINE; HUMAN IGG1;
MONOCLONAL-ANTIBODIES; DENDRITIC CELLS; IN-VIVO; TRANSPORT; CHALLENGE;
IMMUNITY
AB To protect against human immunodeficiency virus (HIV-1) infection, broadly neutralizing antibodies (bnAbs) must be active at the portals of viral entry in the gastrointestinal or cervicovaginal tracts. The localization and persistence of antibodies at these sites is influenced by the neonatal Fc receptor (FcRn)(1,2), whose role in protecting against infection in vivo has not been defined. Here, we show that a bnAb with enhanced FcRn binding has increased gut mucosal tissue localization, which improves protection against lentiviral infection in non-human primates. A bnAb directed to the CD4-binding site of the HIV-1 envelope (Env) protein (denoted VRC01)(3) was modified by site-directed mutagenesis to increase its binding affinity for FcRn. This enhanced FcRn-binding mutant bnAb, denoted VRC01-LS, displayed increased transcytosis across human FcRn-expressing cellular monolayers in vitro while retaining Fc gamma RIIIa binding and function, including antibody-dependent cell-mediated cytotoxicity (ADCC) activity, at levels similar to VRC01 (the wild type). VRC01-LS had a threefold longer serum half-life than VRC01 in non-human primates and persisted in the rectal mucosa even when it was no longer detectable in the serum. Notably, VRC01-LSmediated protection superior to that afforded by VRC01 against intrarectal infection with simian-human immunodeficiency virus (SHIV). These findings suggest that modification of FcRn binding provides a mechanism not only to increase serum half-life but also to enhance mucosal localization that confers immune protection. Mutations that enhance FcRn function could therefore increase the potency and durability of passive immunization strategies to prevent HIV-1 infection.
C1 [Ko, Sung-Youl; Pegu, Amarendra; Rudicell, Rebecca S.; Yang, Zhi-yong; Joyce, M. Gordon; Chen, Xuejun; Wang, Keyun; Bao, Saran; Schmidt, Stephen D.; Todd, John-Paul; Saunders, Kevin O.; Rao, Srinivas S.; Mascola, John R.; Nabel, Gary J.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Kraemer, Thomas D.; Rath, Timo; Blumberg, Richard S.] Harvard Univ, Brigham & Womens Hosp, Div Gastroenterol, Dept Med, Boston, MA 02115 USA.
[Zeng, Ming; Haase, Ashley T.] Univ Minnesota, Sch Med, Dept Microbiol, Minneapolis, MN 55455 USA.
[Penzak, Scott R.] NIH, Clin Pharmacokinet Lab, Dept Pharm, Bethesda, MD 20814 USA.
[Nason, Martha C.] NIAID, Biostat Res Branch, Div Clin Res, NIH, Bethesda, MD 20892 USA.
RP Nabel, GJ (reprint author), Sanofi, 640 Mem Dr, Cambridge, MA 02139 USA.
EM jmascola@nih.gov; Gary.Nabel@sanofi.com
RI Schmidt, Stephen/B-5398-2012;
OI Pegu, Amarendra/0000-0003-3564-6453
FU Intramural Research Program of the Vaccine Research Center, National
Institute of Allergy and Infectious Diseases (NIAID), National
Institutes of Health (NIH); Foundation for the National Institutes of
Health; Collaboration for AIDS Vaccine Discovery (CAVD) award from the
Bill & Melinda Gates Foundation [OPP1039775]; NIH [DK044319, DK051362,
DK053056, DK088199]; Harvard Digestive Diseases Center [DK0034854];
German research foundation (DFG) [RA 2040/1-1]
FX We thank M. Roederer for advice on the design and statistical analysis
of animal studies. This research was supported by the Intramural
Research Program of the Vaccine Research Center, National Institute of
Allergy and Infectious Diseases (NIAID), National Institutes of Health
(NIH), and in part by a grant from the Foundation for the National
Institutes of Health with support from the Collaboration for AIDS
Vaccine Discovery (CAVD), award OPP1039775, from the Bill & Melinda
Gates Foundation. R. S. B. is supported by the NIH (DK044319, DK051362,
DK053056 and DK088199) and the Harvard Digestive Diseases Center
(DK0034854). T. R. is supported by the German research foundation (DFG;
RA 2040/1-1). The findings and conclusions in this report are those of
the authors and do not necessarily reflect the views of the funding
agencies.
NR 37
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U1 5
U2 24
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 30
PY 2014
VL 514
IS 7524
BP 642
EP +
DI 10.1038/nature13612
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AR8BW
UT WOS:000343801500052
PM 25119033
ER
PT J
AU Breman, JG
Johnson, KM
AF Breman, Joel G.
Johnson, Karl M.
TI Ebola Then and Now
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Editorial Material
ID HEMORRHAGIC-FEVER; ZAIRE
C1 [Breman, Joel G.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Johnson, Karl M.] NIH, Fogarty Int Ctr, Portland, OR USA.
RP Breman, JG (reprint author), NIH, Fogarty Int Ctr, Bldg 10, Bethesda, MD 20892 USA.
NR 5
TC 23
Z9 25
U1 2
U2 38
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 OCT 30
PY 2014
VL 371
IS 18
BP 1663
EP 1666
DI 10.1056/NEJMp1410540
PG 4
WC Medicine, General & Internal
SC General & Internal Medicine
GA AR7OG
UT WOS:000343768500002
PM 25207624
ER
PT J
AU Collins, J
Huynh, M
AF Collins, John
Huynh, Minh
TI Estimation of diagnostic test accuracy without full verification: a
review of latent class methods
SO STATISTICS IN MEDICINE
LA English
DT Article
DE no gold standard; latent class model; sensitivity; specificity;
diagnostic testing; review
ID ESTIMATING DISEASE PREVALENCE; SAMPLE-SIZE DETERMINATION; OPERATING
CHARACTERISTIC CURVES; RANDOM EFFECTS MODELS; 2 SCREENING-TESTS;
SIMULATION-BASED TECHNIQUES; CORRELATED BINARY DATA;
SALMON-ANEMIA-VIRUS; MONTE-CARLO METHODS; FALSE-POSITIVE RATE
AB The performance of a diagnostic test is best evaluated against a reference test that is without error. For many diseases, this is not possible, and an imperfect reference test must be used. However, diagnostic accuracy estimates may be biased if inaccurately verified status is used as the truth. Statistical models have been developed to handle this situation by treating disease as a latent variable. In this paper, we conduct a systematized review of statistical methods using latent class models for estimating test accuracy and disease prevalence in the absence of complete verification. Published 2014. This article is a U.S. Government work and is in the public domain in the USA.
C1 [Collins, John; Huynh, Minh] NIH, Dept Rehabil Med, Bethesda, MD 20892 USA.
RP Collins, J (reprint author), 6100 Execut Blvd, Bethesda, MD 20892 USA.
EM collinsjp@mail.nih.gov
FU Intramural Research Program of the NIH, Clinical Research Center; Social
Security Administration
FX This research was supported by the Intramural Research Program of the
NIH, Clinical Research Center and through an Inter-Agency Agreement with
the Social Security Administration.
NR 261
TC 14
Z9 14
U1 2
U2 28
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 OCT 30
PY 2014
VL 33
IS 24
BP 4141
EP 4169
DI 10.1002/sim.6218
PG 29
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 AQ6DC
UT WOS:000342897400001
PM 24910172
ER
PT J
AU Baker, SG
AF Baker, Stuart G.
TI A latent class method for diagnostic tests: the new, reference, gold
standard problem
SO STATISTICS IN MEDICINE
LA English
DT Letter
C1 NCI, Biometry Res Grp, Bethesda, MD 20892 USA.
RP Baker, SG (reprint author), NCI, Biometry Res Grp, Bethesda, MD 20892 USA.
EM sb16i@nih.gov
FU Intramural NIH HHS [Z99 CA999999]
NR 3
TC 1
Z9 1
U1 0
U2 2
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 OCT 30
PY 2014
VL 33
IS 24
BP 4320
EP 4320
DI 10.1002/sim.6283
PG 1
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 AQ6DC
UT WOS:000342897400013
PM 25274270
ER
PT J
AU Jones, TI
Yan, C
Sapp, PC
McKenna-Yasek, D
Kang, PB
Quinn, C
Salameh, JS
King, OD
Jones, PL
AF Jones, Takako I.
Yan, Chi
Sapp, Peter C.
McKenna-Yasek, Diane
Kang, Peter B.
Quinn, Colin
Salameh, Johnny S.
King, Oliver D.
Jones, Peter L.
TI Identifying diagnostic DNA methylation profiles for facioscapulohumeral
muscular dystrophy in blood and saliva using bisulfite sequencing
SO CLINICAL EPIGENETICS
LA English
DT Article
DE Bisulfite sequencing; DNA methylation; D4Z4; Disease diagnostics; DUX4;
Epigenetics; Facioscapulohumeral muscular dystrophy; FSHD1; FSHD2
ID SMCHD1 MUTATION; D4Z4; FSHD; REARRANGEMENTS; 4Q; HYPOMETHYLATION;
SUBTELOMERES; EXPRESSION; DISEASE; REPEAT
AB Background: Facioscapulohumeral muscular dystrophy (FSHD) is linked to chromatin relaxation due to epigenetic changes at the 4q35 D4Z4 macrosatellite array. Molecular diagnostic criteria for FSHD are complex and involve analysis of high molecular weight (HMW) genomic DNA isolated from lymphocytes, followed by multiple restriction digestions, pulse-field gel electrophoresis (PFGE), and Southern blotting. A subject is genetically diagnosed as FSHD1 if one of the 4q alleles shows a contraction in the D4Z4 array to below 11 repeats, while maintaining at least 1 repeat, and the contraction is in cis with a disease-permissive A-type subtelomere. FSHD2 is contraction-independent and cannot be diagnosed or excluded by this common genetic diagnostic procedure. However, FSHD1 and FSHD2 are linked by epigenetic deregulation, assayed as DNA hypomethylation, of the D4Z4 array on FSHD-permissive alleles. We have developed a PCR-based assay that identifies the epigenetic signature for both types of FSHD, distinguishing FSHD1 from FSHD2, and can be performed on genomic DNA isolated from blood, saliva, or cultured cells.
Results: Samples were obtained from healthy controls or patients clinically diagnosed with FSHD, and include both FSHD1 and FSHD2. The genomic DNAs were subjected to bisulfite sequencing analysis for the distal 4q D4Z4 repeat with an A-type subtelomere and the DUX4 5' promoter region. We compared genomic DNA isolated from saliva and blood from the same individuals and found similar epigenetic signatures. DNA hypomethylation was restricted to the contracted 4qA chromosome in FSHD1 patients while healthy control subjects were hypermethylated. Candidates for FSHD2 showed extreme DNA hypomethylation on the 4qA DUX4 gene body as well as all analyzed DUX4 5' sequences. Importantly, our assay does not amplify the D4Z4 arrays with non-permissive B-type subtelomeres and accurately excludes the arrays with non-permissive A-type subtelomeres.
Conclusions: We have developed an assay to identify changes in DNA methylation on the pathogenic distal 4q D4Z4 repeat. We show that the DNA methylation profile of saliva reflects FSHD status. This assay can distinguish FSHD from healthy controls, differentiate FSHD1 from FSHD2, does not require HMW genomic DNA or PFGE, and can be performed on either cultured cells, tissue, blood, or saliva samples.
C1 [Jones, Takako I.; Yan, Chi; King, Oliver D.; Jones, Peter L.] Univ Massachusetts, Sch Med, Wellstone Program, Worcester, MA 01655 USA.
[Jones, Takako I.; Yan, Chi; King, Oliver D.; Jones, Peter L.] Univ Massachusetts, Sch Med, Dept Cell & Dev Biol, Worcester, MA 01655 USA.
[Yan, Chi] Huazhong Agr Univ, Coll Anim Sci & Technol, Minist Agr, Key Lab Swine Genet & Breeding, Wuhan 430070, Peoples R China.
[Sapp, Peter C.; McKenna-Yasek, Diane; Quinn, Colin; Salameh, Johnny S.; King, Oliver D.; Jones, Peter L.] Univ Massachusetts, Sch Med, Dept Neurol, Worcester, MA 01655 USA.
[Kang, Peter B.] Univ Florida, Coll Med, Div Pediat Neurol, Dept Pediat, Gainesville, FL 32607 USA.
[Quinn, Colin] Hosp Univ Penn, Dept Neurol, Philadelphia, PA 19104 USA.
[King, Oliver D.; Jones, Peter L.] Univ Massachusetts, Sch Med, Sen Paul Wellstone Muscular Dystrophy Cooperat Re, Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Worcester, MA 01655 USA.
RP Jones, TI (reprint author), Univ Massachusetts, Sch Med, Wellstone Program, 55 Lake Ave North, Worcester, MA 01655 USA.
EM takako.jones@umassmed.edu; peter.jones@umassmed.edu
FU National Institute of Arthritis, Musculoskeletal and Skin Diseases NIH
[R01AR062587]; Senator Paul D. Wellstone Muscular Dystrophy Cooperative
Research Center from the Eunice Kennedy Shriver National Institute for
Child Health and Human Development [U54HD060848]; Muscular Dystrophy
Association [MDA216652]; Chinese Scholarship Council (CSC) [R01AR062587,
201306760041]; Howard Hughes Medical Institute in the Department of
Biology at the Massachusetts Institute of Technology
FX The authors thank the participating subjects and their families, and
Drs. Kathryn R. Wagner and Genila Bibat (Kennedy-Krieger Institute and
Johns Hopkins School of Medicine) for initially collecting the clinical
samples for the Wellstone Center repository [6], Dr. Jennifer C.J. Chen
for establishing the Wellstone Center cell cultures, and Dr. Charis L.
Himeda for helpful comments on the manuscript. This work was funded by
grant R01AR062587 from the National Institute of Arthritis,
Musculoskeletal and Skin Diseases NIH awarded to PLJ. ODK is supported
by the Senator Paul D. Wellstone Muscular Dystrophy Cooperative Research
Center grant U54HD060848 from the Eunice Kennedy Shriver National
Institute for Child Health and Human Development. TIJ was supported by
grant MDA216652 from the Muscular Dystrophy Association. CY was
supported by the Chinese Scholarship Council (CSC) File No. 201306760041
and grant R01AR062587 (PLJ). PCS was supported through the auspices of
Dr. H. Robert Horvitz, an Investigator at the Howard Hughes Medical
Institute in the Department of Biology at the Massachusetts Institute of
Technology. In addition, we thank the Chris Carrino Foundation for FSHD
and the FSH Society for their continued support. The funding agencies
played no role in the design, collection, analysis, or interpretation of
data, or in the decision to publish this study.
NR 36
TC 12
Z9 12
U1 0
U2 2
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1868-7083
J9 CLIN EPIGENETICS
JI Clin. Epigenetics
PD OCT 29
PY 2014
VL 6
AR 23
DI 10.1186/1868-7083-6-23
PG 16
WC Oncology
SC Oncology
GA AW3PJ
UT WOS:000346198500001
PM 25400706
ER
PT J
AU Esposito, G
Nakazawa, J
Ogawa, S
Stival, R
Kawashima, A
Putnick, DL
Bornstein, MH
AF Esposito, Gianluca
Nakazawa, Jun
Ogawa, Shota
Stival, Rita
Kawashima, Akiko
Putnick, Diane L.
Bornstein, Marc H.
TI Baby, You Light-Up My Face: Culture-General Physiological Responses to
Infants and Culture-Specific Cognitive Judgements of Adults
SO PLOS ONE
LA English
DT Article
ID NATURALISTIC EXCHANGES; FACIAL ATTRACTIVENESS; SKIN TEMPERATURE;
UNITED-STATES; MOTHER; ATTENTION; EXPOSURE; CUTENESS; SCHEMA; CORTEX
AB Infants universally elicit in adults a set of solicitous behaviors that are evolutionarily important for the survival of the species. However, exposure, experience, and prejudice appear to govern adults' social choice and ingroup attitudes towards other adults. In the current study, physiological arousal and behavioral judgments were assessed while adults processed unfamiliar infant and adult faces of ingroup vs. outgroup members in two contrasting cultures, Japan and Italy. Physiological arousal was investigated using the novel technique of infrared thermography and behavioral judgments using ratings. We uncovered a dissociation between physiological and behavioral responses. At the physiological level, both Japanese and Italian adults showed significant activation (increase of facial temperature) for both ingroup and outgroup infant faces. At the behavioral level, both Japanese and Italian adults showed significant preferences for ingroup adults. Arousal responses to infants appear to be mediated by the autonomic nervous system and are not dependent on direct caregiving exposure, but behavioral responses appear to be mediated by higher-order cognitive processing based on social acceptance and cultural exposure.
C1 [Esposito, Gianluca; Stival, Rita] Univ Trento, Dept Psychol & Cognit Sci, Rovereto, TN, Italy.
[Esposito, Gianluca] Nanyang Technol Univ, Sch Humanities & Social Sci, Div Psychol, Singapore 639798, Singapore.
[Nakazawa, Jun] Chiba Univ, Fac Educ, Dept Dev Sci, Chiba, Japan.
[Ogawa, Shota] Tokyo Gakugei Univ, United Grad Sch Educ, Chiba, Japan.
[Kawashima, Akiko] Tokyo Univ Social Welf, Sch Social Welf, Tokyo, Japan.
[Putnick, Diane L.; Bornstein, Marc H.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
RP Esposito, G (reprint author), Univ Trento, Dept Psychol & Cognit Sci, Rovereto, TN, Italy.
EM gianluca.esposito@unitn.it; Marc_H_Bornstein@nih.gov
OI Putnick, Diane/0000-0002-6323-749X
FU Japan Society for the Promotion of Science [JSPS PE09064, 22530694,
24730563, 26285149]; FPR Program (RIKEN Brain Science Institute);
National Institutes of Health (NIH), NICHD (USA)
FX This research was supported by the ST fellowship from Japan Society for
the Promotion of Science (JSPS PE09064), Grant-in-aid for Scientific
Research from Japan Society for the Promotion of Science (Projects
#22530694, #24730563, and #26285149), the FPR Program (RIKEN Brain
Science Institute), and the Intramural Research Program of the National
Institutes of Health (NIH), NICHD (USA). The funders had no role in
study design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 46
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U1 0
U2 6
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD OCT 29
PY 2014
VL 9
IS 10
AR e106705
DI 10.1371/journal.pone.0106705
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AT8TG
UT WOS:000345204200001
PM 25353362
ER
PT J
AU LaMontagne, DS
Mugisha, E
Pan, Y
Kumakech, E
Ssemaganda, A
Kemp, TJ
Cover, J
Pinto, LA
Safaeian, M
AF LaMontagne, D. Scott
Mugisha, Emmanuel
Pan, Yuanji
Kumakech, Edward
Ssemaganda, Aloysius
Kemp, Troy J.
Cover, Jane
Pinto, Ligia A.
Safaeian, Mahboobeh
TI Immunogenicity of bivalent HPV vaccine among partially vaccinated young
adolescent girls in Uganda
SO VACCINE
LA English
DT Article
DE HPV vaccine; Adolescents; Immunogenicity; Partially vaccinated; Uganda
ID PAPILLOMAVIRUS-16/18 AS04-ADJUVANTED VACCINE; CERVICAL-CANCER VACCINE;
AGED 10-14 YEARS; PARTICLE VACCINE; INCOME COUNTRIES; HEALTHY GIRLS;
HIGH COVERAGE; FOLLOW-UP; SAFETY; TRIAL
AB Background: Investigations of vaccine efficacy and immunogenicity for adult females receiving fewer than three doses of human papillomavirus (HPV) vaccine have suggested protection against infection and precancerous lesions. We investigated the immunogenicity of bivalent HPV vaccines among adolescent girls from Uganda who received one, two, or three vaccine doses.
Methods: Young girls vaccinated through a government program in Uganda were invited to participate. HPV16- and HPV18-specific antibodies were measured at >= 24 months after the last vaccine dose using an enzyme linked immunoassay in girls who received one (n = 36), two (n = 145), or three (n = 195) doses.
Results: Nearly all subjects (99%) were HPV16 and HPV18 seropositive at the time of blood-draw. Geometric mean antibody levels (GMTs) were: HPV16(1-dose) = 230 EU/mL, HPV16(2-dose) = 808 EU/mL, and HPV16(3-dose) = 1607 EU/mL; HPV18(1-dose) = 87 EU/mL, HPV18(2-dose) = 270 EU/mL, and HPV18(3-dose) = 296 EU/mL. The GMT ratio for 2:3 doses was 0.50 (HPV16) and 0.68 (HPV18) and did not meet the non-inferiority criteria (i.e., lower bound of 97.5% confidence interval of the GMT ratio greater than 0.50). The GMT ratio for 1:3 doses for HPV16 and HPV18 was inferior, but absolute GMTs for one dose were higher than adult women who received one dose (HPV16 = 124 EU/mL, HPV18 = 69 EU/mL) where efficacy has been demonstrated.
Conclusions: Even though immunogenicity with less than three doses did not meet a priori non-inferiority thresholds, antibody levels measured >= 24 months after last dose were similar to those of adult women who have been followed for more than eight years for efficacy. (C) 2014 Published by Elsevier Ltd.
C1 [LaMontagne, D. Scott; Cover, Jane] PATH, Seattle, WA 98121 USA.
[Mugisha, Emmanuel; Kumakech, Edward; Cover, Jane] PATH, Kampala, Uganda.
[Pan, Yuanji; Safaeian, Mahboobeh] NCI, Bethesda, MD 20892 USA.
[Ssemaganda, Aloysius] Uganda Virus Res Inst, UVRI IAVI HIV Vaccine Program, Entebbe, Uganda.
[Kemp, Troy J.; Pinto, Ligia A.] Leidos Biomed Res Inc, HPV Immunol Lab, Frederick Natl Lab Canc Res, Frederick, MD USA.
RP LaMontagne, DS (reprint author), PATH, 2201 Westlake Ave,Suite 200, Seattle, WA 98121 USA.
EM slamontagne@path.org; safaeianm@mail.nih.gov
OI Ssemaganda, Aloysius/0000-0003-4377-5220
FU Bill & Melinda Gates Foundation; National Cancer Institute, National
Institutes of Health [HHSN261200800001E]
FX Funding: This work was supported by a grant to PATH from the Bill &
Melinda Gates Foundation. The content of this publication does not
necessarily reflect the views or policies of the Bill & Melinda Gates
Foundation. This study was also funded in part with federal funds from
the National Cancer Institute, National Institutes of Health, under
Contract No. HHSN261200800001E. The content of this publication does not
necessarily reflect the views or policies of the Department of Health
and Human Services, nor does mention of trade names, commercial
products, or organizations imply endorsement by the US Government.
NR 48
TC 5
Z9 5
U1 0
U2 1
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 OCT 29
PY 2014
VL 32
IS 47
BP 6303
EP 6311
DI 10.1016/j.vaccine.2014.08.071
PG 9
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA AS3YQ
UT WOS:000344211400017
PM 25218297
ER
PT J
AU Choyke, PL
AF Choyke, Peter L.
TI Nanoparticles: Take Only Pictures, Leave Only Footprints
SO SCIENCE TRANSLATIONAL MEDICINE
LA English
DT Editorial Material
ID MOLECULES; PARTICLES
AB A phase I study of a tumor-targeted nanoshell in five patients documents an important milestone in the development of nanoparticles for molecular imaging in humans
C1 NCI, Mol Imaging Program, Bethesda, MD 20892 USA.
RP Choyke, PL (reprint author), NCI, Mol Imaging Program, Bldg 10, Bethesda, MD 20892 USA.
EM pchoyke@nih.gov
NR 10
TC 1
Z9 1
U1 0
U2 4
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 1946-6234
EI 1946-6242
J9 SCI TRANSL MED
JI Sci. Transl. Med.
PD OCT 29
PY 2014
VL 6
IS 260
AR 260fs44
DI 10.1126/scitranslmed.aaa0614
PG 3
WC Cell Biology; Medicine, Research & Experimental
SC Cell Biology; Research & Experimental Medicine
GA AR9TR
UT WOS:000343920500002
PM 25355696
ER
PT J
AU Robertson, FC
Berzofsky, JA
Terabe, M
AF Robertson, Faith C.
Berzofsky, Jay A.
Terabe, Masaki
TI NKT cell networks in the regulation of tumor immunity
SO FRONTIERS IN IMMUNOLOGY
LA English
DT Review
DE NKT cell; tumor immunology; immune regulation; immune network; NKT cell
subsets
ID KILLER-T-CELLS; GROWTH-FACTOR-BETA; LIGAND ALPHA-GALACTOSYLCERAMIDE;
ANTIGEN-PRESENTING CELLS; DENDRITIC CELLS; IN-VIVO; ANTITUMOR IMMUNITY;
ANERGY INDUCTION; MEDIATED IMMUNOTHERAPY; FUNCTIONALLY DISTINCT
AB CD1d-restricted natural killer T (NKT) cells lie at the interface between the innate and adaptive immune systems and are important mediators of immune responses and tumor immunosurveillance. These NKT cells uniquely recognize lipid antigens, and their rapid yet specific reactions influence both innate and adaptive immunity. In tumor immunity, two NKT subsets (type I and type II) have contrasting roles in which they not only cross-regulate one another, but also impact innate immune cell populations, including natural killer, dendritic, and myeloid lineage cells, as well as adaptive populations, especially CD8(+) and CD4(+) T cells. The extent to which NKT cells promote or suppress surrounding cells affects the host's ability to prevent neoplasia and is consequently of great interest for therapeutic development. Data have shown the potential for therapeutic use of NKT cell agonists and synergy with immune response modifiers in both pre-clinical studies and preliminary clinical studies. However, there is room to improve treatment efficacy by further elucidating the biological mechanisms underlying NKT cell networks. Here, we discuss the progress made in understanding NKT cell networks, their consequent role in the regulation of tumor immunity, and the potential to exploit that knowledge in a clinical setting.
C1 [Robertson, Faith C.; Berzofsky, Jay A.; Terabe, Masaki] NCI, Vaccine Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Berzofsky, JA (reprint author), NCI, Vaccine Branch, Ctr Canc Res, NIH, Bldg 41,Room D702D, Bethesda, MD 20892 USA.
EM berzofsk@helix.nih.gov
FU Gui Foundation; National Cancer Institute, Center for Cancer Research;
Intramural Research Program of the NIH
FX This work was supported by the Intramural Research Program of the NIH,
National Cancer Institute, Center for Cancer Research and the Gui
Foundation.
NR 125
TC 7
Z9 7
U1 2
U2 12
PU FRONTIERS RESEARCH FOUNDATION
PI LAUSANNE
PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND
SN 1664-3224
J9 FRONT IMMUNOL
JI Front. Immunol.
PD OCT 28
PY 2014
VL 5
AR UNSP 542
DI 10.3389/fimmu.2014.00543
PG 12
WC Immunology
SC Immunology
GA CI1OC
UT WOS:000354512500001
ER
PT J
AU Ascierto, PA
Grimaldi, AM
Anderson, AC
Bifulco, C
Cochran, A
Garbe, C
Eggermont, AM
Faries, M
Ferrone, S
Gershenwald, JE
Gajewski, TF
Halaban, R
Hodi, FS
Kefford, R
Kirkwood, JM
Larkin, J
Leachman, S
Maio, M
Marais, R
Masucci, G
Melero, I
Palmieri, G
Puzanov, I
Ribas, A
Saenger, Y
Schilling, B
Seliger, B
Stroncek, D
Sullivan, R
Testori, A
Wang, E
Ciliberto, G
Mozzillo, N
Marincola, FM
Thurin, M
AF Ascierto, Paolo A.
Grimaldi, Antonio M.
Anderson, Ana Carrizosa
Bifulco, Carlo
Cochran, Alistair
Garbe, Claus
Eggermont, Alexander M.
Faries, Mark
Ferrone, Soldano
Gershenwald, Jeffrey E.
Gajewski, Thomas F.
Halaban, Ruth
Hodi, F. Stephen
Kefford, Richard
Kirkwood, John M.
Larkin, James
Leachman, Sancy
Maio, Michele
Marais, Richard
Masucci, Giuseppe
Melero, Ignacio
Palmieri, Giuseppe
Puzanov, Igor
Ribas, Antoni
Saenger, Yvonne
Schilling, Bastian
Seliger, Barbara
Stroncek, David
Sullivan, Ryan
Testori, Alessandro
Wang, Ena
Ciliberto, Gennaro
Mozzillo, Nicola
Marincola, Francesco M.
Thurin, Magdalena
TI Future perspectives in melanoma research: meeting report from the
"Melanoma Bridge", Napoli, December 5th-8th 2013
SO JOURNAL OF TRANSLATIONAL MEDICINE
LA English
DT Article
ID STAGE-IV MELANOMA; PRIMARY CUTANEOUS MELANOMA; IMPROVES EARLY-DETECTION;
ADOPTIVE CELL TRANSFER; METASTATIC MELANOMA; TUMOR MICROENVIRONMENT;
ACQUIRED-RESISTANCE; MEK INHIBITION; BRAF INHIBITOR;
MONOCLONAL-ANTIBODIES
AB The fourth "Melanoma Bridge Meeting" took place in Naples, December 5 to 8th, 2013. The four topics discussed at this meeting were: Diagnosis and New Procedures, Molecular Advances and Combination Therapies, News in Immunotherapy, and Tumor Microenvironment and Biomarkers. Until recently systemic therapy for metastatic melanoma patients was ineffective, but recent research 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). New therapies, such as mitogen-activated protein kinase (MAPK) pathway inhibitors, like BRAF and MEK inhibitors, as well as other signaling pathways inhibitors, are being tested in metastatic melanoma either as monotherapy or in combination, and have yielded promising results. Improved survival rates have also been observed with immune therapy for patients with metastatic melanoma. Immune-modulating antibodies came to the forefront with anti-CTLA-4, programmed cell death-1 (PD-1) and PD-1 ligand 1 (PD-L1) pathway blocking antibodies that result in durable responses in a subset of melanoma patients. Agents targeting other immune inhibitory (e. g., Tim-3) or immune stimulating (e. g., CD137) receptors and other approaches such as adoptive cell transfer demonstrate clinical benefit in melanoma as well. This meeting's specific focus was on advances in targeted therapy and immunotherapy. Both combination targeted therapy approaches and different immunotherapies were discussed. Similarly to the previous meetings, the importance of biomarkers for clinical application as markers for diagnosis, prognosis and prediction of treatment response was an integral part of the meeting. Significant consideration was given to issues surrounding the development of novel therapeutic targets as further study of patterns of resistance to both immunologic and targeted drugs are paramount to future drug development to guide existing and future therapies. The overall emphasis on biomarkers supports novel concepts toward integrating biomarkers into contemporary clinical management 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.
C1 [Ascierto, Paolo A.; Grimaldi, Antonio M.; Ciliberto, Gennaro; Mozzillo, Nicola] Fdn G Pascale, Ist Nazl Tumori, Naples, Italy.
[Anderson, Ana Carrizosa] Harvard Univ, Sch Med, Ctr Neurol Dis, Boston, MA USA.
[Bifulco, Carlo] Providence Canc Ctr, Earle A Chiles Res Inst, Portland, OR USA.
[Cochran, Alistair] Univ Calif Los Angeles, John Wayne Canc Inst, David Geffen Sch Med, Dept Pathol & Lab Med, Santa Monica, CA USA.
[Cochran, Alistair] Univ Calif Los Angeles, John Wayne Canc Inst, David Geffen Sch Med, Dept Surg, Santa Monica, CA USA.
[Garbe, Claus] Univ Tubingen, Dept Dermatol, Ctr Dermato Oncol, Tubingen, Germany.
[Eggermont, Alexander M.] Canc Inst Gustave Roussy, Villejuif, France.
[Faries, Mark] John Wayne Canc Inst, Donald L Morton Melanoma Res Program, Santa Monica, CA USA.
[Ferrone, Soldano] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA USA.
[Gershenwald, Jeffrey E.] Univ Texas MD Anderson Canc Ctr, Dept Surg Oncol, Houston, TX 77030 USA.
[Gajewski, Thomas F.] Univ Chicago Med, Immunol & Canc Program, Dept Med, Chicago, IL USA.
[Gajewski, Thomas F.] Univ Chicago Med, Immunol & Canc Program, Dept Pathol, Chicago, IL USA.
[Halaban, Ruth] Yale Univ, Sch Med, Dept Dermatol, New Haven, CT 06510 USA.
[Hodi, F. Stephen] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Kefford, Richard] Univ Sydney, Westmead Millennium Inst, Westmead Inst Canc Res, Sydney, NSW 2006, Australia.
[Kefford, Richard] Univ Sydney, Melanoma Inst Australia, Sydney, NSW 2006, Australia.
[Kirkwood, John M.] Univ Pittsburgh, Sch Med, Div Hematol Oncol, Dept Med, Pittsburgh, PA USA.
[Kirkwood, John M.] Univ Pittsburgh, Sch Med, Div Hematol Oncol, Dept Dermatol, Pittsburgh, PA USA.
[Kirkwood, John M.] Univ Pittsburgh, Sch Med, Div Hematol Oncol, Dept Translat Sci, Pittsburgh, PA USA.
[Kirkwood, John M.] Pittsburgh Canc Inst, Melanoma Program, Pittsburgh, PA 15213 USA.
[Larkin, James] Royal Marsden NHS Fdn Trust, London, England.
[Leachman, Sancy] Oregon Hlth & Sci Univ, Dept Dermatol, Portland, OR USA.
[Maio, Michele] Ist Toscano Tumori, Univ Hosp Siena, Dept Oncol, Siena, Italy.
[Marais, Richard] Paterson Inst Canc Res, Mol Oncol Grp, Manchester M20 4BX, Lancs, England.
[Masucci, Giuseppe] Karolinska Hosp, Dept Oncol Pathol, S-10401 Stockholm, Sweden.
[Melero, Ignacio] Univ Navarra Clin, Ctr Invest Med Aplicada, Navarra, Spain.
[Palmieri, Giuseppe] CNR, Inst Biomol Chem, Unit Canc Genet, Sassari, Italy.
[Puzanov, Igor] Vanderbilt Univ, Med Ctr, Nashville, TN USA.
[Ribas, Antoni] Univ Calif Los Angeles, David Geffen Sch Med, JCCC, Tumor Immunol Program, Los Angeles, CA 90095 USA.
[Saenger, Yvonne] Icahn Sch Med Mt Sinai, Dept Dermatol, Tisch Canc Inst, Div Hematol & Oncol, New York, NY 10029 USA.
[Schilling, Bastian] Univ Duisburg Essen, West German Canc Ctr, Univ Hosp, Dept Dermatol, Essen, Germany.
[Seliger, Barbara] Univ Halle Wittenberg, Inst Med Immunol, D-06108 Halle, Germany.
[Stroncek, David] NIH, Cell Proc Sect, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA.
[Sullivan, Ryan] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Melanoma,Canc Ctr, Boston, MA USA.
[Testori, Alessandro] Ist Europeo Oncol, Milan, Italy.
[Wang, Ena] Sidra Med & Res Ctr, Div Chief Translat Med, Doha, Qatar.
[Marincola, Francesco M.] Sidra Med & Res Ctr, Doha, Qatar.
[Thurin, Magdalena] NCI, Canc Diag Program, NIH, Bethesda, MD 20892 USA.
[Schilling, Bastian] German Canc Consortium DKTK, Heidelberg, Germany.
RP Ascierto, PA (reprint author), Fdn G Pascale, Ist Nazl Tumori, Naples, Italy.
EM paolo.ascierto@gmail.com; thurinm@mail.nih.gov
OI Masucci, Giuseppe/0000-0002-9583-2306; Ciliberto,
Gennaro/0000-0003-2851-8605; Palmieri, Giuseppe/0000-0002-4350-2276;
MELERO BERMEJO, IGNACIO/0000-0002-1360-348X
FU Fondazione Melanoma Onlus; Society of ImmunoTherapy of Cancer (SITC)
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
to Michael Hoetzel for providing us with the group picture from the
meeting.
NR 124
TC 6
Z9 6
U1 2
U2 10
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 OCT 28
PY 2014
VL 12
AR 277
DI 10.1186/s12967-014-0277-z
PG 29
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA AT8FX
UT WOS:000345170400001
PM 25348889
ER
PT J
AU McArdle, PF
Kittner, SJ
Ay, H
Brown, RD
Meschia, JF
Rundek, T
Wassertheil-Smoller, S
Woo, D
Andsberg, G
Biffi, A
Brenner, DA
Cole, JW
Corriveau, R
de Bakker, PIW
Delavaran, H
Dichgans, M
Grewal, RP
Gwinn, K
Huq, M
Jern, C
Jimenez-Conde, J
Jood, K
Kaplan, RC
Katschnig, P
Katsnelson, M
Labovitz, DL
Lemmens, R
Li, LX
Lindgren, A
Markus, HS
Peddareddygari, LR
Pedersen, A
Pera, J
Redfors, P
Roquer, J
Rosand, J
Rost, NS
Rothwell, PM
Sacco, RL
Sharma, P
Slowik, A
Sudlow, C
Thijs, V
Tiedt, S
Valenti, R
Worrall, BB
AF McArdle, Patrick F.
Kittner, Steven J.
Ay, Hakan
Brown, Robert D., Jr.
Meschia, James F.
Rundek, Tatjana
Wassertheil-Smoller, Sylvia
Woo, Daniel
Andsberg, Gunnar
Biffi, Alessandro
Brenner, David A.
Cole, John W.
Corriveau, Roderick
de Bakker, Paul I. W.
Delavaran, Hossein
Dichgans, Martin
Grewal, Raji P.
Gwinn, Katrina
Huq, Mohammed
Jern, Christina
Jimenez-Conde, Jordi
Jood, Katarina
Kaplan, Robert C.
Katschnig, Petra
Katsnelson, Michael
Labovitz, Daniel L.
Lemmens, Robin
Li, Linxin
Lindgren, Arne
Markus, Hugh S.
Peddareddygari, Leema R.
Pedersen, Annie
Pera, Joanna
Redfors, Petra
Roquer, Jaume
Rosand, Jonathan
Rost, Natalia S.
Rothwell, Peter M.
Sacco, Ralph L.
Sharma, Pankaj
Slowik, Agnieszka
Sudlow, Cathie
Thijs, Vincent
Tiedt, Steffen
Valenti, Raffaella
Worrall, Bradford B.
CA NINDS SiGN Study
TI Agreement between TOAST and CCS ischemic stroke classification The NINDS
SiGN Study
SO NEUROLOGY
LA English
DT Article
ID CAUSATIVE CLASSIFICATION; SYSTEM; RELIABILITY; SUBTYPES; TRIAL
AB Objective: The objective of this study was to assess the level of agreement between stroke subtype classifications made using the Trial of Org 10172 Acute Stroke Treatment (TOAST) and Causative Classification of Stroke (CCS) systems.
Methods: Study subjects included 13,596 adult men and women accrued from 20 US and European genetic research centers participating in the National Institute of Neurological Disorders and Stroke (NINDS) Stroke Genetics Network (SiGN). All cases had independently classified TOAST and CCS stroke subtypes. Kappa statistics were calculated for the 5 major ischemic stroke subtypes common to both systems.
Results: The overall agreement between TOAST and CCS was moderate (agreement rate, 70%; kappa = 0.59, 95% confidence interval [CI] 0.58-0.60). Agreement varied widely across study sites, ranging from 28% to 90%. Agreement on specific subtypes was highest for large-artery atherosclerosis (kappa = 0.71, 95% CI 0.69-0.73) and lowest for small-artery occlusion (kappa = 0.56, 95% CI 0.54-0.58).
Conclusion: Agreement between TOAST and CCS diagnoses was moderate. Caution is warranted when comparing or combining results based on the 2 systems. Replication of study results, for example, genome-wide association studies, should utilize phenotypes determined by the same classification system, ideally applied in the same manner.
C1 [McArdle, Patrick F.] Univ Maryland, Sch Med, Div Endocrinol Diabet & Nutr, College Pk, MD USA.
[Kittner, Steven J.; Cole, John W.; Huq, Mohammed] Univ Maryland, College Pk, MD USA.
[Ay, Hakan] Harvard Univ, Massachusetts Gen Hosp, Dept Neurol, Med Sch, Cambridge, MA 02138 USA.
[Ay, Hakan] Harvard Univ, Massachusetts Gen Hosp, Dept Radiol, Med Sch, Cambridge, MA 02138 USA.
[Brown, Robert D., Jr.] Mayo Clin, Rochester, MN USA.
[Meschia, James F.] Mayo Clin Florida, Jacksonville, FL USA.
[Rundek, Tatjana; Katsnelson, Michael; Sacco, Ralph L.] Univ Miami, Coral Gables, FL 33124 USA.
[Wassertheil-Smoller, Sylvia; Kaplan, Robert C.; Labovitz, Daniel L.] Albert Einstein Coll Med, Bronx, NY USA.
[Woo, Daniel] Univ Cincinnati, Cincinnati, OH 45221 USA.
[Andsberg, Gunnar; Delavaran, Hossein; Lindgren, Arne] Skane Univ Hosp, Lund, Sweden.
[Biffi, Alessandro; Rosand, Jonathan; Rost, Natalia S.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Biffi, Alessandro; Rosand, Jonathan; Rost, Natalia S.] Broad Inst, Cambridge, MA USA.
[Brenner, David A.] Univ Alabama Birmingham, Birmingham, AL USA.
[Corriveau, Roderick; Gwinn, Katrina] NINDS, NIH, Bethesda, MD 20892 USA.
[de Bakker, Paul I. W.] Univ Med Ctr Utrecht, Utrecht, Netherlands.
[Dichgans, Martin; Tiedt, Steffen] Univ Munich, Klinikum Univ Munchen, Inst Stroke & Dementia Res, Munich, Germany.
[Dichgans, Martin] Munich Cluster Syst Neurol SyNergy, Munich, Germany.
[Grewal, Raji P.; Peddareddygari, Leema R.] St Francis Med Ctr, Neurosci Inst, Lynwood, CA USA.
[Jern, Christina; Jood, Katarina; Pedersen, Annie; Redfors, Petra] Univ Gothenburg, Sahlgrenska Acad, Gothenburg, Sweden.
[Jimenez-Conde, Jordi; Roquer, Jaume] IMIM Hosp Univ del Mar, Barcelona, Spain.
[Katschnig, Petra] Med Univ Graz, Graz, Austria.
[Lemmens, Robin; Thijs, Vincent] VIB, Neurobiol Lab, Vesalius Res Ctr, Leuven, Belgium.
[Lemmens, Robin; Thijs, Vincent] Univ Leuven KU Leuven, Expt Neurol Dept Neurosci, Louvain, Belgium.
[Lemmens, Robin; Thijs, Vincent] Univ Leuven KU Leuven, Leuven Res Inst Neurosci & Dis LIND, Louvain, Belgium.
[Lemmens, Robin; Thijs, Vincent] Univ Hosp Leuven, Dept Neurol, Louvain, Belgium.
[Li, Linxin] Univ Oxford, Oxford OX1 2JD, England.
[Lindgren, Arne] Lund Univ, S-22100 Lund, Sweden.
[Markus, Hugh S.; Valenti, Raffaella] St Georges Univ London, London, England.
[Pera, Joanna; Slowik, Agnieszka] Jagiellonian Univ, Coll Med, PL-31007 Krakow, Poland.
[Rothwell, Peter M.] Univ Oxford, Nuffield Dept Clin Neurosci, Oxford, England.
[Rothwell, Peter M.] John Radcliffe Hosp, Oxford OX3 9DU, England.
[Sharma, Pankaj] Univ London Imperial Coll Sci Technol & Med, London SW7 2AZ, England.
[Sudlow, Cathie] Univ Edinburgh, Edinburgh EH8 9YL, Midlothian, Scotland.
[Worrall, Bradford B.] Univ Virginia Hlth Syst, Dept Neurol, Charlottesville, VA 22908 USA.
[Worrall, Bradford B.] Univ Virginia Hlth Syst, Dept Hlth Evaluat Sci, Charlottesville, VA USA.
RP Worrall, BB (reprint author), Univ Virginia Hlth Syst, Dept Neurol, Charlottesville, VA 22908 USA.
EM bbw9r@virginia.edu
RI de Bakker, Paul/B-8730-2009; Thijs, Vincent/C-3647-2009; JIMENEZ-CONDE,
JORDI/C-1941-2012
OI de Bakker, Paul/0000-0001-7735-7858; Thijs, Vincent/0000-0002-6614-8417;
FU National Institute of Neurological Disorders and Stroke (NINDS) [U01
NS069208]
FX The SiGN Network was funded by a cooperative agreement grant from the
National Institute of Neurological Disorders and Stroke (NINDS): U01
NS069208. Funding for network members is presented in appendix e-1 on
the Neurology (R) Web site at Neurology.org.
NR 15
TC 8
Z9 8
U1 0
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0028-3878
EI 1526-632X
J9 NEUROLOGY
JI Neurology
PD OCT 28
PY 2014
VL 83
IS 18
BP 1653
EP 1660
PG 8
WC Clinical Neurology
SC Neurosciences & Neurology
GA AT3RU
UT WOS:000344852200015
PM 25261504
ER
PT J
AU Hagberg, KW
McGlynn, KA
Sahasrabuddhe, VV
Jick, S
AF Hagberg, K. W.
McGlynn, K. A.
Sahasrabuddhe, V. V.
Jick, S.
TI Anti-diabetic medications and risk of primary liver cancer in persons
with type II diabetes
SO BRITISH JOURNAL OF CANCER
LA English
DT Article
DE metformin; insulin; oral hypoglycaemic; liver cancer
ID PRACTICE RESEARCH DATABASE; HEPATOCELLULAR-CARCINOMA; REDUCED RISK;
HEPATITIS-C; METFORMIN; METAANALYSIS; ASSOCIATION; MELLITUS; INSULIN;
COHORT
AB Background: Type II diabetes increases liver cancer risk but the risk may be mitigated by anti-diabetic medications. However, choice of medications is correlated with diabetes duration and severity, leading to confounding by indication.
Methods: To address this association, we conducted a nested case-control study among persons with type II diabetes in the Clinical Practice Research Datalink. Cases had primary liver cancer and controls were matched on age, sex, practice, calendar time, and number of years in the database. Exposure was classified by type and combination of anti-diabetic prescribed and compared to non-use. Odds ratios (ORs) and 95% confidence intervals (95% CI) were calculated using conditional logistic regression.
Results: In 305 cases of liver cancer and 1151 controls, there was no association between liver cancer and anti-diabetic medication use compared to non-use (OR = 0.74 (95% CI = 0.45-1.20) for metformin-only, 1.10 (95% CI = 0.66-1.84) for other oral hypoglycaemic (OH)-only, 0.89 (95% CI = 0.58-1.37) for metformin + other OH, 1.11 (95% CI = 0.60-2.05) for metformin + insulin, 0.81 (95% CI = 0.23-2.85) for other OH + insulin, and 0.72 (95% CI = 0.18-2.84) for insulin-only). Stratification by duration of diabetes did not alter the results.
Conclusions: Use of any anti-diabetic medications in patients with type II diabetes was not associated with liver cancer, though there was a suggestion of a small protective effect for metformin.
C1 [Hagberg, K. W.; Jick, S.] Boston Collaborat Drug Surveillance Program, Lexington, MA 02421 USA.
[Hagberg, K. W.; Jick, S.] Boston Univ, Sch Publ Hlth, Lexington, MA 02421 USA.
[McGlynn, K. A.; Sahasrabuddhe, V. V.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
RP Hagberg, KW (reprint author), Boston Collaborat Drug Surveillance Program, 11 Muzzey St, Lexington, MA 02421 USA.
EM khagberg@bu.edu
RI CPRD, CPRD/B-9594-2017
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. KWH and SJ
received funding for completion of this project. VVS and KAM are
employed by the National Cancer Institute.
NR 25
TC 8
Z9 8
U1 0
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 OCT 28
PY 2014
VL 111
IS 9
BP 1710
EP 1717
DI 10.1038/bjc.2014.447
PG 8
WC Oncology
SC Oncology
GA AS9NF
UT WOS:000344568600006
PM 25093492
ER
PT J
AU Cavalier, MC
Pierce, AD
Wilder, PT
Alasady, MJ
Hartman, KG
Neau, DB
Foley, TL
Jadhav, A
Maloney, DJ
Simeonov, A
Toth, EA
Weber, DJ
AF Cavalier, Michael C.
Pierce, Adam D.
Wilder, Paul T.
Alasady, Milad J.
Hartman, Kira G.
Neau, David B.
Foley, Timothy L.
Jadhav, Ajit
Maloney, David J.
Simeonov, Anton
Toth, Eric A.
Weber, David J.
TI Covalent Small Molecule Inhibitors of Ca2+-Bound S100B
SO BIOCHEMISTRY
LA English
DT Article
ID CALCIUM-BINDING PROTEIN; NUCLEAR-MAGNETIC-RESONANCE; MALIGNANT-MELANOMA;
METASTATIC MELANOMA; REGULATORY DOMAIN; NMR-SPECTROSCOPY; CANCER-CELLS;
P53; S100B(BETA-BETA); SURVIVAL
AB Elevated levels of the tumor marker S100B are observed in malignant melanoma, and this EF-hand-containing protein was shown to directly bind wild-type (wt) p53 in a Ca2+-dependent manner, dissociate the p53 tetramer, and inhibit its tumor suppression functions. Likewise, inhibiting S100B with small interfering RNA (siRNA(S100B)) is sufficient to restore wild-type p53 levels and its downstream gene products and induce the arrest of cell growth and UV-dependent apoptosis in malignant melanoma. Therefore, it is a goal to develop S100B inhibitors (SBiXs) that inhibit the S100Bp53 complex and restore active p53 in this deadly cancer. Using a structureactivity relationship by nuclear magnetic resonance approach (SAR by NMR), three persistent binding pockets are found on S100B, termed sites 13. While inhibitors that simultaneously bind sites 2 and 3 are in place, no molecules that simultaneously bind all three persistent sites are available. For this purpose, Cys84 was used in this study as a potential means to bridge sites 1 and 2 because it is located in a small crevice between these two deeper pockets on the protein. Using a fluorescence polarization competition assay, several Cys84-modified S100B complexes were identified and examined further. For five such SBiXS100B complexes, crystallographic structures confirmed their covalent binding to Cys84 near site 2 and thus present straightforward chemical biology strategies for bridging sites 1 and 3. Importantly, one such compound, SC1982, showed an S100B-dependent death response in assays with WM115 malignant melanoma cells, so it will be particularly useful for the design of SBiX molecules with improved affinity and specificity.
C1 [Cavalier, Michael C.; Pierce, Adam D.; Wilder, Paul T.; Alasady, Milad J.; Hartman, Kira G.; Toth, Eric A.; Weber, David J.] Univ Maryland, Sch Med, Dept Biochem & Mol Biol, CBT, Baltimore, MD 21201 USA.
[Wilder, Paul T.; Toth, Eric A.; Weber, David J.] Univ Maryland, Sch Med, Marlene & Stewart Greenebaum Canc Ctr, Baltimore, MD 21201 USA.
[Neau, David B.] Cornell Univ, NE CAT, Argonne, IL 60439 USA.
[Foley, Timothy L.; Jadhav, Ajit; Maloney, David J.; Simeonov, Anton] NIH, Natl Ctr Adv Translat Sci, Bethesda, MD 20892 USA.
RP Weber, DJ (reprint author), Univ Maryland, Sch Med, Dept Biochem & Mol Biol, Biomed Res Facil, Rm 439,108 N Greene St, Baltimore, MD 21201 USA.
EM dweber@som.umaryland.edu
OI Cavalier, Michael/0000-0001-7336-1219
FU National Institutes of Health, National Institute of General Medical
Sciences; U.S. DOE; U.S. DOE, Office of Science and Office of Basic
Energy
FX Research conducted at the Advanced Photon Source on the Northeastern
Collaborative Access Team beamlines is supported by the National
Institutes of Health, National Institute of General Medical Sciences.
Use of the Advanced Photon Source, an Office of Science User Facility
operated for the U.S. Department of Energy (DOE) Office of Science by
Argonne National Laboratory, was supported by the U.S. DOE. Use of the
Stanford Synchrotron Radiation Lightsource, SLAC National Accelerator
Laboratory, is supported by the U.S. DOE, Office of Science and Office
of Basic Energy. The SSRL Structural Molecular Biology Program is
supported by the DOE Office of Biological and Environmental Research and
by the National Institutes of Health, National Institute of General
Medical Sciences.
NR 75
TC 9
Z9 9
U1 1
U2 7
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0006-2960
J9 BIOCHEMISTRY-US
JI Biochemistry
PD OCT 28
PY 2014
VL 53
IS 42
BP 6628
EP 6640
DI 10.1021/bi5005552
PG 13
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA AS0DZ
UT WOS:000343949800002
PM 25268459
ER
PT J
AU Hoang, DT
Matsunari, H
Nagaya, M
Nagashima, H
Millis, JM
Witkowski, P
Periwal, V
Hara, M
Jo, J
AF Hoang, Danh-Tai
Matsunari, Hitomi
Nagaya, Masaki
Nagashima, Hiroshi
Millis, J. Michael
Witkowski, Piotr
Periwal, Vipul
Hara, Manami
Jo, Junghyo
TI A Conserved Rule for Pancreatic Islet Organization
SO PLOS ONE
LA English
DT Article
ID CELL-ADHESION; CONFOCAL MICROSCOPY; INSULIN-SECRETION; BETA-CELLS;
ARCHITECTURE; LANGERHANS; AGGREGATION; ORGANOGENESIS; MORPHOGENESIS;
MICROANATOMY
AB Morphogenesis, spontaneous formation of organism structure, is essential for life. In the pancreas, endocrine alpha, beta, and delta cells are clustered to form islets of Langerhans, the critical micro-organ for glucose homeostasis. The spatial organization of endocrine cells in islets looks different between species. Based on the three-dimensional positions of individual cells in islets, we computationally inferred the relative attractions between cell types, and found that the attractions between homotypic cells were slightly, but significantly, stronger than the attractions between heterotypic cells commonly in mouse, pig, and human islets. The difference between alpha - beta cell attraction and beta - beta cell attraction was minimal in human islets, maximizing the plasticity of islet structures. Our result suggests that although the cellular composition and attractions of pancreatic endocrine cells are quantitatively different between species, the physical mechanism of islet morphogenesis may be evolutionarily conserved.
C1 [Hoang, Danh-Tai; Jo, Junghyo] Asia Pacific Ctr Theoret Phys, Pohang, South Korea.
[Matsunari, Hitomi; Nagaya, Masaki; Nagashima, Hiroshi] Meiji Univ, Int Inst Bioresource Res, Kanagawa, Japan.
[Millis, J. Michael; Witkowski, Piotr] Univ Chicago, Dept Surg, Chicago, IL 60637 USA.
[Periwal, Vipul] NIDDK, Lab Biol Modeling, NIH, Bethesda, MD USA.
[Hara, Manami] Univ Chicago, Dept Med, Chicago, IL 60637 USA.
[Jo, Junghyo] POSTECH, Dept Phys, Pohang, South Korea.
RP Hara, M (reprint author), Univ Chicago, Dept Med, 5841 S Maryland Ave, Chicago, IL 60637 USA.
EM mhara@uchicago.edu; jojunghyo@apctp.org
RI Jo, Junghyo/D-4889-2011
FU Basic Science Research Program through the National Foundation of Korea
- Ministry of Science, ICT & Future Planning [2013R1A1A1006655]; Max
Planck Society; Korea Ministry of Education, Science and Technology;
Gyeongsangbuk-Do and Pohang City; Intramural Research Program of the
NIH; National Institute of Diabetes and Digestive and Kidney Diseases;
[DK-020595]; [DK-072473]; [AG-042151]
FX This research was supported in part 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 (J.J.), the Intramural Research Program
of the NIH, the National Institute of Diabetes and Digestive and Kidney
Diseases (V. P.), and DK-020595 to the University of Chicago Diabetes
Research and Training Center (Animal Models Core), DK-072473, AG-042151,
and a gift from the Kovler Family Foundation (M. H.). The funders had no
role in study design, data collection and analysis, decision to publish,
or preparation of the manuscript.
NR 36
TC 5
Z9 5
U1 0
U2 6
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD OCT 28
PY 2014
VL 9
IS 10
AR e110384
DI 10.1371/journal.pone.0110384
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AS0BH
UT WOS:000343943100026
PM 25350558
ER
PT J
AU Campbell-Washburn, AE
Rogers, T
Xue, H
Hansen, MS
Lederman, RJ
Faranesh, AZ
AF Campbell-Washburn, Adrienne E.
Rogers, Toby
Xue, Hui
Hansen, Michael S.
Lederman, Robert J.
Faranesh, Anthony Z.
TI Dual echo positive contrast bSSFP for real-time visualization of passive
devices during magnetic resonance guided cardiovascular catheterization
SO JOURNAL OF CARDIOVASCULAR MAGNETIC RESONANCE
LA English
DT Article
DE Interventional MR; Cardiovascular magnetic resonance; Positive contrast;
White marker; Guidewire; Real-time; Variable flip angle
ID STATE FREE PRECESSION; INTERVENTIONAL MRI; CELLS; IRON; ADULTS; SIGNAL;
WIRES
AB Background: Cardiovascular magnetic resonance (CMR) guided cardiovascular catheterizations can potentially reduce ionizing radiation exposure and enable new interventions. Commercially available paramagnetic X-Ray devices create a small signal void in CMR images, which is ambiguous and insufficient to guide catheterization procedures. This work aims to improve real-time CMR of off-the-shelf X-Ray devices by developing a real-time positive contrast sequence with color overlay of the device onto anatomy.
Methods: A dual-echo bSSFP sequence was used to generate both a dephased positive contrast image and bSSFP image simultaneously. A variable flip angle scheme was implemented to reduce the specific absorption rate (SAR) and hence device heating. Image processing was used to isolate the device from background signal, and the device was overlaid in color on the anatomy, mimicking active device visualization. Proof-of-concept experiments were performed using a commercially available nitinol guidewire for left heart catheterization in Yorkshire swine.
Results: The dual echo pulse sequence generated a temporal resolution of 175 ms (5.7 frames/second) with GRAPPA acceleration factor 4. Image processing was performed in real-time and color overlay of the device on the anatomy was displayed to the operator with no latency. The color overlay accurately depicted the guidewire location, with minimal background contamination, during left heart catheterization.
Conclusions: The ability to effectively visualize commercially available X-Ray devices during CMR-guided cardiovascular catheterizations, combined with safe low-SAR pulse sequences, could potentially expedite the clinical translation of interventional CMR.
C1 [Campbell-Washburn, Adrienne E.; Rogers, Toby; Xue, Hui; Hansen, Michael S.; Lederman, Robert J.; Faranesh, Anthony Z.] NHLBI, Div Intramural Res, Cardiovasc & Pulm Branch, NIH, Bethesda, MD 20892 USA.
RP Campbell-Washburn, AE (reprint author), NHLBI, Div Intramural Res, Cardiovasc & Pulm Branch, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM adrienne.campbell@nih.gov
RI Hansen, Michael/J-5391-2015;
OI Hansen, Michael/0000-0002-8087-8731; Rogers, Toby/0000-0002-6043-3137;
lederman, robert/0000-0003-1202-6673
FU National Heart, Lung and Blood Institute Division of Intramural Research
[Z01-HL006039-01, Z01-HL005062-08]
FX This work was supported by the National Heart, Lung and Blood Institute
Division of Intramural Research, Z01-HL006039-01 and Z01-HL005062-08.
RJL is the principal investigator on a US government Cooperative
Research and Development Agreement (CRADA) with Siemens Medical
Solutions.
NR 26
TC 6
Z9 6
U1 0
U2 2
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 OCT 28
PY 2014
VL 16
AR 88
DI 10.1186/s12968-014-0088-7
PG 7
WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical
Imaging
SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine &
Medical Imaging
GA AS3QF
UT WOS:000344192700001
PM 25359137
ER
PT J
AU Du, CW
Volkow, ND
Koretsky, AP
Pan, Y
AF Du, Congwu
Volkow, Nora D.
Koretsky, Alan P.
Pan, Yingtian
TI Low-frequency calcium oscillations accompany deoxyhemoglobin
oscillations in rat somatosensory cortex
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE spontaneous low-frequency brain oscillations; resting-state functional
connectivity; neuronal calcium; cerebral hemodynamic; neuroimaging
ID STATE FUNCTIONAL CONNECTIVITY; LEVEL-DEPENDENT FLUCTUATIONS;
NEAR-INFRARED SPECTROSCOPY; CEREBRAL BLOOD VOLUME; BRAIN IN-VIVO;
HEMODYNAMIC-RESPONSE; OXYGEN-CONSUMPTION; ALPHA-CHLORALOSE;
VISUAL-CORTEX; BOLD SIGNALS
AB Spontaneous low-frequency oscillations (LFOs) of blood-oxygenlevel- dependent (BOLD) signals are used to map brain functional connectivity with functional MRI, but their source is not well understood. Here we used optical imaging to assess whether LFOs from vascular signals covary with oscillatory intracellular calcium (Ca-i(2+)) and with local field potentials in the rat's somatosensory cortex. We observed that the frequency of Ca-i(2+) oscillations in tissue (similar to 0.07 Hz) was similar to the LFOs of deoxyhemoglobin (HbR) and oxyhemoglobin (HbO2) in both large blood vessels and capillaries. The HbR and HbO2 fluctuations within tissue correlated with Ca-i(2+) oscillations with a lag time of similar to 5-6 s. The Ca-i(2+) and hemoglobin oscillations were insensitive to hypercapnia. In contrast, cerebral-blood-flow velocity (CBFv) in arteries and veins fluctuated at a higher frequency (similar to 0.12 Hz) and was sensitive to hypercapnia. However, in parenchymal tissue, CBFv oscillated with peaks at both similar to 0.06 Hz and similar to 0.12 Hz. Although the higher-frequency CBFv oscillation (similar to 0.12 Hz) was decreased by hypercapnia, its lower-frequency component (similar to 0.06 Hz) was not. The sensitivity of the higher CBFV oscillations to hypercapnia, which triggers blood vessel vasodilation, suggests its dependence on vascular effects that are distinct from the LFOs detected in HbR, HbO(2), Ca-i(2+), and the lower-frequency tissue CBFv, which were insensitive to hypercapnia. Hemodynamic LFOs correlated both with Ca-i(2+) and neuronal firing (local field potentials), indicating that they directly reflect neuronal activity (perhaps also glial). These findings show that HbR fluctuations (basis of BOLD oscillations) are linked to oscillatory cellular activity and detectable throughout the vascular tree (arteries, capillaries, and veins).
C1 [Du, Congwu; Pan, Yingtian] SUNY Stony Brook, Dept Biomed Engn, Stony Brook, NY 11794 USA.
[Volkow, Nora D.] NIAAA, NIH, Bethesda, MD 20892 USA.
[Koretsky, Alan P.] NINDS, Lab Funct & Mol Imaging, NIH, Bethesda, MD 20892 USA.
RP Du, CW (reprint author), SUNY Stony Brook, Dept Biomed Engn, Stony Brook, NY 11794 USA.
EM Congwu.Du@stonybrook.edu
RI Koretsky, Alan/C-7940-2015
OI Koretsky, Alan/0000-0002-8085-4756
FU NIH [K25-DA021200, 1RC1DA028534, R21DA032228, R01DA029718]
FX We thank Dr. H. Ren, W. Chen, and J. Li for partially assisting with
data representation; K. Park for assisting with animal handling; Dr. Z.
Luo for laser speckle contrast imaging; S. Sundaresh for assisting with
in vitro studies; and Dr. J.R. Walters [National Institute of
Neurological Disorders and Stroke, National Institutes of Health (NIH)]
for helpful discussions. This research was supported in part by NIH
Grants K25-DA021200 (to C.D.), 1RC1DA028534 (to C.D. and Y.P.),
R21DA032228 (to Y.P. and C.D.), and R01DA029718 (to C. D. and Y.P.) and
by the NIH intramural program (N.D.V. and A.P.K.).
NR 56
TC 10
Z9 10
U1 1
U2 21
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 OCT 28
PY 2014
VL 111
IS 43
BP E4677
EP E4686
DI 10.1073/pnas.1410800111
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AR6ZL
UT WOS:000343729500019
PM 25313035
ER
PT J
AU Gorkovskiy, A
Thurber, KR
Tycko, R
Wickner, RB
AF Gorkovskiy, Anton
Thurber, Kent R.
Tycko, Robert
Wickner, Reed B.
TI Locating folds of the in-register parallel beta-sheet of the Sup35p
prion domain infectious amyloid
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE [PSI plus ] prion; solid-state NMR; dipolar recoupling; amyloid; Sup35
ID SOLID-STATE NMR; NUCLEAR-MAGNETIC-RESONANCE; HET-S PRION; YEAST PRION;
SACCHAROMYCES-CEREVISIAE; STRUCTURAL BASIS; HETEROKARYON
INCOMPATIBILITY; PODOSPORA-ANSERINA; FIBRIL STRUCTURE; CORE STRUCTURE
AB The [PSI+] prion is a self-propagating amyloid of the translation termination factor, Sup35p, of Saccharomyces cerevisiae. The N-terminal 253 residues (NM) of this 685-residue protein normally function in regulating mRNA turnover but spontaneously form infectious amyloid in vitro. We converted the three Ile residues in Sup35NM to Leu and then replaced 16 single residues with Ile, one by one, and prepared Ile-1-C-13 amyloid of each mutant, seeding with amyloid formed by the reference sequence Sup35NM. Using solid-state NMR, we showed that 10 of the residues examined, including six between residues 30 and 90, showed the similar to 0.5-nm distance between labels diagnostic of the in-register parallel amyloid architecture. The five scattered N domain residues with wider spacing may be in turns or loops; one is a control at the C terminus of M. All mutants, except Q56I, showed little or no [PSI+] transmission barrier from the reference sequence, suggesting that they could assume a similar amyloid architecture in vitro when seeded with filaments of reference sequence Sup35NM. Infection of yeast cells expressing the reference SUP35 gene sequence with amyloid of several mutants produced [PSI+] transfectants with similar efficiency as did reference sequence Sup35NM amyloid. Our work provides a stringent demonstration that the Sup35 prion domain has the folded in-register parallel beta-sheet architecture and suggests common locations of the folds. This architecture naturally suggests a mechanism of inheritance of conformation, the central mystery of prions.
C1 [Gorkovskiy, Anton; Wickner, Reed B.] NIDDK, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA.
[Thurber, Kent R.; Tycko, Robert] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
RP Wickner, RB (reprint author), NIDDK, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA.
EM wickner@helix.nih.gov
RI Gorkovskiy, Anton/J-8930-2016
OI Gorkovskiy, Anton/0000-0003-4811-2282
FU Intramural Program of the National Institute of Diabetes and Digestive
and Kidney Diseases
FX This work was supported by the Intramural Program of the National
Institute of Diabetes and Digestive and Kidney Diseases.
NR 64
TC 11
Z9 11
U1 4
U2 22
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 OCT 28
PY 2014
VL 111
IS 43
BP E4615
EP E4622
DI 10.1073/pnas.1417974111
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AR6ZL
UT WOS:000343729500012
PM 25313080
ER
PT J
AU Loc, WS
Smith, JP
Matters, G
Kester, M
Adair, JH
AF Loc, Welley S.
Smith, Jill P.
Matters, Gail
Kester, Mark
Adair, James H.
TI Novel strategies for managing pancreatic cancer
SO WORLD JOURNAL OF GASTROENTEROLOGY
LA English
DT Article
DE Pancreatic cancer; Diagnosis; Treatment; Signaling pathways;
Nanomedicine; Biomarkers
ID PHOSPHATE NANOCOMPOSITE PARTICLES; OPIOID GROWTH-FACTOR;
CALCIUM-PHOSPHATE; DRUG-DELIVERY; DUCTAL ADENOCARCINOMA;
INSULIN-RESISTANCE; RANDOMIZED-TRIAL; BREAST-CANCER; B RECEPTOR;
GEMCITABINE
AB With the incidence reports of pancreatic cancer increasing every year, research over the last several decades has been focused on the means to achieve early diagnosis in patients that are at a high risk of developing the malignancy. This review covers current strategies for managing pancreatic cancer and further discusses efforts in understanding the role of early onset symptoms leading to tumor progression. Recent investigations in this discussion include type 3c diabetes, selected biomarkers and pathways related to pancreatic intraepithelial neoplasia lesions, drug resistance, and advances in nanomedicine which may provide significant solutions for improving early detection and treatments in future medicine. (C) 2014 Baishideng Publishing Group Inc. All rights reserved.
C1 [Loc, Welley S.] Penn State Univ, Dept Chem, University Pk, PA 16802 USA.
[Smith, Jill P.] NIDDK, NIH, Bethesda, MD 20892 USA.
[Smith, Jill P.] Penn State Univ, Coll Med, Dept Med, Hershey, PA 17033 USA.
[Matters, Gail] Penn State Univ, Coll Med, Dept Biochem & Mol Biol, Hershey, PA 17033 USA.
[Kester, Mark; Adair, James H.] Penn State Univ, Coll Med, Dept Pharmacol, Hershey, PA 17033 USA.
[Adair, James H.] Penn State Univ, Dept Mat Sci & Engn, University Pk, PA 16802 USA.
[Adair, James H.] Penn State Univ, Dept Bioengn, University Pk, PA 16802 USA.
RP Adair, JH (reprint author), Penn State Univ, Dept Mat Sci & Engn, 223 Hallowell Bldg, University Pk, PA 16802 USA.
EM jha3@ems.psu.edu
OI Adair, James/0000-0002-7516-5024
FU National Institutes of Health (NIH) R01 [5R01CA167535-02]
FX Supported by the National Institutes of Health (NIH) R01 Grant
5R01CA167535-02
NR 87
TC 2
Z9 2
U1 4
U2 22
PU BAISHIDENG PUBLISHING GROUP INC
PI PLEASANTON
PA 8226 REGENCY DR, PLEASANTON, CA 94588 USA
SN 1007-9327
EI 2219-2840
J9 WORLD J GASTROENTERO
JI World J. Gastroenterol.
PD OCT 28
PY 2014
VL 20
IS 40
BP 14717
EP 14725
DI 10.3748/wjg.v20.i40.14717
PG 9
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA AR9GS
UT WOS:000343881800018
PM 25356034
ER
PT J
AU Seol, HS
Akiyama, Y
Shimada, S
Lee, HJ
Kim, TI
Chun, SM
Singh, SR
Jang, SJ
AF Seol, Hyang Sook
Akiyama, Yoshimitsu
Shimada, Shu
Lee, Hee Jin
Kim, Tae Im
Chun, Sung Min
Singh, Shree Ram
Jang, Se Jin
TI Epigenetic silencing of microRNA-373 to epithelial-mesenchymal
transition in non-small cell lung cancer through IRAK2 and LAMP1 axes
SO CANCER LETTERS
LA English
DT Article
DE microRNA-373; Non-small cell lung cancer; Histone deacetylase; Tumor
suppressor; IRAK2; LAMP1
ID LYSOSOMAL MEMBRANE-GLYCOPROTEINS; CPG ISLAND METHYLATION; DNA
METHYLATION; TUMOR SUPPRESSORS; MIRNA EXPRESSION; COLON-CANCER;
CARCINOMA; CARCINOGENESIS; PROLIFERATION; PROGRESSION
AB The role of microRNAs (miRNAs) in carcinogenesis as tumor suppressors or oncogenes has been widely reported. Epigenetic change is one of the mechanisms of transcriptional silencing of miRNAs in cancer. To identify lung cancer-related miRNAs that are mediated by histone modification, we conducted microarray analysis in the Calu-6 non-small cell lung cancer (NSCLC) cell line after treatment with suberoylanilide hydroxamic acid (SAHA), a histone deacetylase (HDAC) inhibitor. The expression level of miR-373 was enhanced by SAHA treatment in this cell line by microarray and the following quantitative RT-PCR analyses. Treatment with another HDAC inhibitor, Trichostatin A, restored the levels of miR-373 expression in A549 and Calu-6 cells, while demethylation drug treatment did not. Importantly, miR-373 was found to be down-regulated in NSCLC tissues and cell lines. Transfection of miR-373 into A549 and Calu-6 cells attenuated cell proliferation, migration, and invasion and reduced the expression of mesenchymal markers. Additional microarray analysis of miR-373-transfected cells and computational predictions identified IRAK2 and LAMP1 as targets of miR-373. Knockdown of these two genes showed similar biological effects to those of miR-373 overexpression. In clinical samples, overexpression of IRAK2 correlated with decreased disease-free survival of patients with non-adenocarcinoma. In conclusion, we found that miR-373 is silenced by histone modification in lung cancer cells and identified its function as a tumor suppressor and negative regulator of the mesenchymal phenotype through downstream IRAK2 and LAMP1 target genes. Published by Elsevier Ireland Ltd.
C1 [Seol, Hyang Sook; Lee, Hee Jin; Chun, Sung Min; Jang, Se Jin] Univ Ulsan, Coll Med, Asan Med Ctr, Dept Pathol, Seoul 138736, South Korea.
[Seol, Hyang Sook; Kim, Tae Im; Chun, Sung Min; Jang, Se Jin] Univ Ulsan, Coll Med, Asan Med Ctr, Asan Ctr Canc Genome Discovery, Seoul 138736, South Korea.
[Akiyama, Yoshimitsu; Shimada, Shu] Tokyo Med & Dent Univ, Grad Sch Med & Dent Sci, Dept Mol Oncol, Tokyo 1138519, Japan.
[Singh, Shree Ram] NCI, Basic Res Lab, Ctr Canc Res, Frederick, MD 21702 USA.
RP Singh, SR (reprint author), NCI, Basic Res Lab, Ctr Canc Res, Frederick, MD 21702 USA.
EM singhshr@mail.nih.gov; jangsejin@amc.seoul.kr
RI Singh, Shree Ram/B-7614-2008
OI Singh, Shree Ram/0000-0001-6545-583X
FU Ministry of Science, ICT and Future Planning [2012R1A1A3011467,
2011-0030105]
FX Basic Science Research Program through the National Research Foundation
of Korea funded by the Ministry of Science, ICT and Future Planning
(2012R1A1A3011467); Leading Foreign Research Institute Recruitment
Program through the National Research Foundation of Korea funded by the
Ministry of Science, ICT and Future Planning (2011-0030105).
NR 64
TC 15
Z9 20
U1 1
U2 13
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 OCT 28
PY 2014
VL 353
IS 2
BP 232
EP 241
DI 10.1016/j.canlet.2014.07.019
PG 10
WC Oncology
SC Oncology
GA AQ5UT
UT WOS:000342874800012
PM 25063738
ER
PT J
AU Georgakilas, AG
Redon, CE
Ferguson, NF
Kryston, TB
Parekh, P
Dickey, JS
Nakamura, AJ
Mitchell, JB
Bonner, WM
Martin, OA
AF Georgakilas, Alexandros G.
Redon, Christophe E.
Ferguson, Nicholas F.
Kryston, Thomas B.
Parekh, Palak
Dickey, Jennifer S.
Nakamura, Asako J.
Mitchell, James B.
Bonner, William M.
Martin, Olga A.
TI Systemic DNA damage accumulation under in vivo tumor growth can be
inhibited by the antioxidant Tempol
SO CANCER LETTERS
LA English
DT Article
DE Tumor-bearing mice; DNA damage; Antioxidants; Tempol; Non-targeted
effects
ID DOUBLE-STRAND BREAKS; OXIDATIVE STRESS; CANCER-CELLS; GENOMIC
INSTABILITY; HYDROGEN-PEROXIDE; BYSTANDER CELLS; INTERCELLULAR
COMMUNICATION; IONIZING-RADIATION; IRRADIATION; LESIONS
AB Recently we found that mice bearing subcutaneous non-metastatic tumors exhibited elevated levels of two types of complex DNA damage, i.e., double-strand breaks and oxidatively-induced clustered DNA lesions in various tissues throughout the body, both adjacent to and distant from the tumor site. This DNA damage was dependent on CCL2, a cytokine involved in the recruitment and activation of macrophages, suggesting that this systemic DNA damage was mediated via tumor-induced chronic inflammatory responses involving cytokines, activation of macrophages, and consequent free radical production. If free radicals are involved, then a diet containing an antioxidant may decrease the distant DNA damage. Here we repeated our standard protocol in cohorts of two syngeneic tumor-bearing C57BL/6NCr mice that were on a Tempol-supplemented diet. We show that double-strand break and oxidatively-induced clustered DNA lesion levels were considerably decreased, about two- to three fold, in the majority of tissues studied from the tumor-bearing mice fed the antioxidant Tempol compared to the control tumor-bearing mice. Similar results were also observed in nude mice suggesting that the Tempol effects are independent of functioning adaptive immunity. This is the first in vivo study demonstrating the effect of a dietary antioxidant on abscopal DNA damage in tissues distant from a localized source of genotoxic stress. These findings may be important for understanding the mechanisms of genomic instability and carcinogenesis caused by chronic stress-induced systemic DNA damage and for developing preventative strategies. (C) 2014 Elsevier Ireland Ltd. All rights reserved.
C1 [Georgakilas, Alexandros G.; Ferguson, Nicholas F.; Kryston, Thomas B.] E Carolina Univ, Thomas Harriot Coll Arts & Sci, Dept Biol, Greenville, NC 27858 USA.
[Georgakilas, Alexandros G.] Natl Tech Univ Athens, Dept Phys, GR-15773 Athens, Greece.
[Redon, Christophe E.; Parekh, Palak; Dickey, Jennifer S.; Nakamura, Asako J.; Bonner, William M.; Martin, Olga A.] NCI, Mol Pharmacol Lab, Ctr Canc Res, Bethesda, MD 20892 USA.
[Dickey, Jennifer S.] US FDA, Off In Vitro Diagnost, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA.
[Nakamura, Asako J.] Ibaraki Univ, Dept Biol Sci, Fac Sci, Ibaraki 3108512, Japan.
[Mitchell, James B.] NCI, Radiat Biol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Martin, Olga A.] Peter MacCallum Canc Ctr, Div Radiat Oncol & Canc Imaging, Melbourne, Vic 3002, Australia.
[Martin, Olga A.] Peter MacCallum Canc Ctr, Lab Mol Radiat Biol, Melbourne, Vic 3002, Australia.
[Martin, Olga A.] Univ Melbourne, Sir Peter MacCallum Dept Oncol, Melbourne, Vic 3002, Australia.
RP Martin, OA (reprint author), Peter MacCallum Canc Ctr, Dept Radiat Oncol & Canc Imaging, Melbourne, Vic 3002, Australia.
EM olga.martin@petermac.org
RI Parekh, Palak/B-7042-2015
OI Parekh, Palak/0000-0001-9201-5194
FU NIH Intramural Program; East Carolina University; EU [MC-CIG-303514];
COST Action [CM1201]; Hellenic National Strategic Reference Framework
(NSRF) - Research Funding Program: THALES [MIS 37946]; O.M.'s Australian
National Health and Medical Research Council (NHMRC) [1027558]
FX We are grateful to the Laboratory Animal Sciences Program and Pathology
Histotechnology Laboratory staff (National Cancer Institute Frederick)
for the help with animal maintenance and histological analysis. We thank
Roger Martin, Peter MacCallum Cancer Centre, for his advice and comments
on the manuscript. This study was partly supported by the NIH Intramural
Program, by A.G.'s funding from East Carolina University, EU grant
MC-CIG-303514, COST Action CM1201 'Biomimetic Radical Chemistry',
Hellenic National Strategic Reference Framework (NSRF) - Research
Funding Program: THALES (Grant number MIS 37946), and by O.M.'s
Australian National Health and Medical Research Council (NHMRC) grant
number 1027558.
NR 91
TC 6
Z9 6
U1 1
U2 14
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 OCT 28
PY 2014
VL 353
IS 2
BP 248
EP 257
DI 10.1016/j.canlet.2014.07.030
PG 10
WC Oncology
SC Oncology
GA AQ5UT
UT WOS:000342874800014
PM 25069035
ER
PT J
AU Israeli, M
Roelen, DL
Carrington, M
Petersdor, EW
Claas, FHJ
Haasnoot, GW
Oudshoorn, M
AF Israeli, Moshe
Roelen, Dave L.
Carrington, Mary
Petersdor, Effie Wang
Claas, Frans H. J.
Haasnoot, Geert W.
Oudshoorn, Machteld
TI Association between CTL precursor frequency to HLA-C mismatches and
HLA-C antigen cell surface expression
SO FRONTIERS IN IMMUNOLOGY
LA English
DT Article
DE cytotoxicT-cell precursor frequency; HLA-C; cell surface expression;
allo-reactiyity; CTLp assay
ID BONE-MARROW-TRANSPLANTATION; KIR LIGAND INCOMPATIBILITY; CLASS-I
MISMATCHES; HIV CONTROL; ALLOREACTIVITY; POLYMORPHISM; NEF;
IDENTIFICATION; SUBSTITUTIONS; INFECTION
AB Previous studies showed the relevance of the cytotoxic T-cell precursor (CTLp) frequency assay for prediction of the outcome of HLA mismatched hematopoietic cell transplantation (HCT). Recently, it has been shown that HLA-C cell surface expression is correlated with virus specific cytotoxicT-cell responses and viremia control in HIV patients. The aim of the current study was to investigate the association between HLA-C antigen expression and the CTLp frequency to the mismatched HLA-C antigen. In total 115 recipient donor pairs, for whom a successful CTLp assay was performed, were evaluated for this pilot study. All donor recipient pairs were matched at 9/10 alleles with a single mismatch at the HLA-C locus. Antigen expression level of the mismatched HLA-C allele for each recipient and donor was based on the mean fluorescence intensity (MFI) values as described by Apps et al. (1). The cell surface expression of recipient's mismatched HLA-C antigen was significantly lower among CTLp negative (n = 59) compared to CTLp positive (n = 56) pairs (154 and 193 MFI units, respectively, p = 0.0031). This difference was more pronounced in donor recipient pairs that were mismatched for amino-acid residue-116 located in the groove of the HLA-C antigen, suggesting that the importance of peptide binding in the allo-recognition. Furthermore, in the particular case of low expression of the recipient mismatched HLA-C antigen (MFI < 115), CTLp reactivity depended on HLA-C expression level in the donor, the median MFI of donor's mismatched HLA-C antigen was 114 in CTLp negative cases (n = 26), while in CTLp positive cases (n = 15) the median MFI of donor's HLA-C antigen was 193 (p = 0.0093). We conclude that the expression level of the donor and recipient mismatched HLA-C antigens affect CTLp outcome. HLA-C antigen expression levels in combination with the CTLp assay may prove useful for the prediction of the clinical outcome of HLA-C mismatched HCT.
C1 [Israeli, Moshe; Roelen, Dave L.; Claas, Frans H. J.; Haasnoot, Geert W.; Oudshoorn, Machteld] Leiden Univ, Med Ctr, Dept Immunohematol & Blood Transfus, NL-2300 RC Leiden, Netherlands.
[Israeli, Moshe] Rabin Med Ctr, Tissue Typing Lab, Petah Tiqwa, Israel.
[Carrington, Mary] Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Canc & Inflammat Program, Expt Immunol Lab, Frederick, MD USA.
[Carrington, Mary] MIT, Massachusetts Gen Hosp, Ragon Inst, Boston, MA USA.
[Carrington, Mary] Harvard Univ, Boston, MA 02115 USA.
[Petersdor, Effie Wang] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98104 USA.
[Oudshoorn, Machteld] Europdonor Fdn, Leiden, Netherlands.
RP Israeli, M (reprint author), Leiden Univ, Med Ctr, Dept Immunohematol & Blood Transfus, Albinusdreef 2, NL-2300 RC Leiden, Netherlands.
EM m.israeli@lumc.nl
FU Frederick National Laboratory for Cancer Research [HHSN261200800001E];
Intramural Research Program of the NIH, Frederick National Lab, Center
for Cancer Research
FX The authors thank Hanneke Kapsenberg for her valuable technical
performance of CTLp tests and the cellular lab of the section of
Immunogenetics and Transplantation Immunology for processing the blood
samples. This project has been funded in whole or in part with federal
funds from the Frederick National Laboratory for Cancer Research, 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, or does mention of trade names, commercial products,
or organizations imply endorsement by the U.S. Government. This Research
was supported in part by the Intramural Research Program of the NIH,
Frederick National Lab, Center for Cancer Research.
NR 32
TC 3
Z9 3
U1 0
U2 2
PU FRONTIERS RESEARCH FOUNDATION
PI LAUSANNE
PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND
SN 1664-3224
J9 FRONT IMMUNOL
JI Front. Immunol.
PD OCT 27
PY 2014
VL 5
AR 547
DI 10.3389/fimmu.2014.00547
PG 7
WC Immunology
SC Immunology
GA CI1NS
UT WOS:000354511500001
PM 25386183
ER
PT J
AU Oppenheim, JJ
AF Oppenheim, Joost J.
TI Evolution of the serendipitous discovery of macrophage-lymphocyte
interactions
SO FRONTIERS IN IMMUNOLOGY
LA English
DT Editorial Material
DE lymphocytes; dendritic cells; macrophages; antigen presentation; chronic
lymphocytic leukemic cells
ID PIG T-LYMPHOCYTES; ANTIGEN RECOGNITION; BOUND ANTIGENS; TRANSFORMATION;
CELLS
C1 NCI, Lab Mol Immunol, NIH, Frederick, MD 21701 USA.
RP Oppenheim, JJ (reprint author), NCI, Lab Mol Immunol, NIH, Frederick, MD 21701 USA.
EM oppenhej@mail.nih.gov
NR 10
TC 0
Z9 0
U1 0
U2 1
PU FRONTIERS RESEARCH FOUNDATION
PI LAUSANNE
PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND
SN 1664-3224
J9 FRONT IMMUNOL
JI Front. Immunol.
PD OCT 27
PY 2014
VL 5
AR 530
DI 10.3389/fimmu.2014.00530
PG 2
WC Immunology
SC Immunology
GA CI1IV
UT WOS:000354498100001
PM 25386177
ER
PT J
AU Kohr, MJ
Murphy, E
Steenbergen, C
AF Kohr, Mark J.
Murphy, Elizabeth
Steenbergen, Charles
TI Glyceraldehyde-3-Phosphate Dehydrogenase Acts as a Mitochondrial
Trans-S-Nitrosylase in the Heart
SO PLOS ONE
LA English
DT Article
ID NITRIC-OXIDE SYNTHASE; CYCLOPHILIN D; CELL-DEATH; PROTEIN; GAPDH;
PHOSPHORYLATION; IDENTIFICATION; NITROSATION; MYOCARDIUM; ACTIVATION
AB Mitochondrial proteins have been shown to be common targets of S-nitrosylation (SNO), but the existence of a mitochondrial source of nitric oxide remains controversial. SNO is a nitric oxide-dependent thiol modification that can regulate protein function. Interestingly, trans-S-nitrosylation represents a potential pathway for the import of SNO into the mitochondria. The glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH), which has been shown to act as a nuclear trans-S-nitrosylase, has also been shown to enter mitochondria. However, the function of GAPDH in the mitochondria remains unknown. Therefore, we propose the hypothesis that S-nitrosylated GAPDH (SNO-GAPDH) interacts with mitochondrial proteins as a trans-S-nitrosylase. In accordance with this hypothesis, SNO-GAPDH should be detected in mitochondrial fractions, interact with mitochondrial proteins, and increase mitochondrial SNO levels. Our results demonstrate a four-fold increase in GAPDH levels in the mitochondrial fraction of mouse hearts subjected to ischemic preconditioning, which increases SNO-GAPDH levels. Co-immunoprecipitation studies performed in mouse hearts perfused with the S-nitrosylating agent S-nitrosoglutathione (GSNO), suggest that SNO promotes the interaction of GAPDH with mitochondrial protein targets. The addition of purified SNO-GAPDH to isolated mouse heart mitochondria demonstrated the ability of SNO-GAPDH to enter the mitochondrial matrix, and to increase SNO for many mitochondrial proteins. Further, the overexpression of GAPDH in HepG2 cells increased SNO for a number of different mitochondrial proteins, including heat shock protein 60, voltage-dependent anion channel 1, and acetyl-CoA acetyltransferase, thus supporting the role of GAPDH as a potential mitochondrial trans-S-nitrosylase. In further support of this hypothesis, many of the mitochondrial SNO proteins identified with GAPDH overexpression were no longer detected with GAPDH knock-down or mutation. Therefore, our results suggest that SNO-GAPDH can act as a mitochondrial trans-S-nitrosylase, thereby conferring the transfer of SNO from the cytosol to the mitochondria.
C1 [Kohr, Mark J.; Steenbergen, Charles] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA.
[Kohr, Mark J.; Murphy, Elizabeth] NHLBI, Syst Biol Ctr, NIH, Bethesda, MD 20892 USA.
RP Kohr, MJ (reprint author), Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA.
EM mkohr1@jhmi.edu
OI Kohr, Mark/0000-0002-6034-5962
FU American Heart Association [12BGIA11780030]; National Heart, Lung and
Blood Institute/National Institutes of Health [1K99HL114721,
5R01HL039752]; National Heart, Lung and Blood Institute/National
Institutes of Health Intramural Program [ZO1HL006059, ZO1HL002066]
FX This work was supported by the American Heart Association
(12BGIA11780030, MK), National Heart, Lung and Blood Institute/National
Institutes of Health grants 1K99HL114721 (MK) and 5R01HL039752 (CS), and
the National Heart, Lung and Blood Institute/National Institutes of
Health Intramural Program (ZO1HL006059 and ZO1HL002066, EM). The funders
had no role in study design, data collection and analysis, decision to
publish, or preparation of the manuscript.
NR 31
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Z9 7
U1 1
U2 7
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD OCT 27
PY 2014
VL 9
IS 10
AR e111448
DI 10.1371/journal.pone.0111448
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AZ1JF
UT WOS:000347994900075
PM 25347796
ER
PT J
AU Yu, GQ
Dye, BA
Gail, MH
Shi, J
Klepac-Ceraj, V
Paster, BJ
Wang, GQ
Wei, WQ
Fan, JH
Qiao, YL
Dawsey, SM
Freedman, ND
Abnet, CC
AF Yu, Guoqin
Dye, Bruce A.
Gail, Mitchell H.
Shi, Jianxin
Klepac-Ceraj, Vanja
Paster, Bruce J.
Wang, Guo-Qing
Wei, Wen-Qiang
Fan, Jin-Hu
Qiao, You-Lin
Dawsey, Sanford M.
Freedman, Neal D.
Abnet, Christian C.
TI The association between the upper digestive tract microbiota by HOMIM
and oral health in a population-based study in Linxian, China
SO BMC PUBLIC HEALTH
LA English
DT Article
DE Microbiota; Oral health; Dental caries; Periodontitis; Bleeding on
probe; Attachment loss
ID HUMAN SUBGINGIVAL PLAQUE; BACTERIAL DIVERSITY; PERIODONTAL-DISEASE;
MOLECULAR ANALYSIS; CHILDHOOD CARIES; RISK INDICATORS; PERMANENT TEETH;
ATTACHMENT LOSS; DENTAL-CARIES; COMMUNITY
AB Background: Bacteria affect oral health, but few studies have systematically examined the role of bacterial communities in oral diseases. We examined this relationship in a large population-based Chinese cancer screening cohort.
Methods: Human Oral Microbe Identification Microarrays were used to test for the presence of 272 human oral bacterial species (97 genera) in upper digestive tract (UDT) samples collected from 659 participants. Oral health was assessed using US NHANES (National Health and Nutrition Examination Survey) protocols. We assessed both dental health (total teeth missing; tooth decay; and the decayed, missing, and filled teeth (DMFT) score) and periodontal health (bleeding on probing (BoP) extent score, loss of attachment extent score, and a periodontitis summary estimate).
Results: Microbial richness, estimated by number of genera per sample, was positively correlated with BoP score (P = 0.015), but negatively correlated with tooth decay and DMFT score (P = 0.008 and 0.022 respectively). Regarding beta-diversity, as estimated by the UniFrac distance matrix for pairwise differences among samples, at least one of the first three principal components of the UniFrac distance matrix was correlated with the number of missing teeth, tooth decay, DMFT, BoP, or periodontitis. Of the examined genera, Parvimonas was positively associated with BoP and periodontitis. Veillonellacease [G-1] was associated with a high DMFT score, and Filifactor and Peptostreptococcus were associated with a low DMFT score.
Conclusions: Our results suggest distinct relationships between UDT microbiota and dental and periodontal health. Poor dental health was associated with a less microbial diversity, whereas poor periodontal health was associated with more diversity and the presence of potentially pathogenic species.
C1 [Yu, Guoqin; Gail, Mitchell H.; Shi, Jianxin; Dawsey, Sanford M.; Freedman, Neal D.; Abnet, Christian C.] NCI, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20852 USA.
[Dye, Bruce A.] Ctr Dis Control & Prevent, Natl Ctr Hlth Stat, Hyattsville, MD 20782 USA.
[Klepac-Ceraj, Vanja; Paster, Bruce J.] Forsyth Inst, Cambridge, MA USA.
[Klepac-Ceraj, Vanja] Wellesley Coll, Wellesley, MA 02181 USA.
[Paster, Bruce J.] Harvard Univ, Sch Dent Med, Boston, MA 02115 USA.
[Wang, Guo-Qing; Wei, Wen-Qiang; Fan, Jin-Hu; Qiao, You-Lin] Chinese Acad Med Sci, Inst Canc, Beijing 100021, Peoples R China.
[Yu, Guoqin] NCI, Div Canc Epidemiol & Genet, Genet Epidemiol Branch, Bethesda, MD 20892 USA.
RP Yu, GQ (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20852 USA.
EM yug3@mail.nih.gov
RI Freedman, Neal/B-9741-2015; Abnet, Christian/C-4111-2015; Qiao,
You-Lin/B-4139-2012
OI Freedman, Neal/0000-0003-0074-1098; Abnet,
Christian/0000-0002-3008-7843; Qiao, You-Lin/0000-0001-6380-0871
FU Intramural Research Program of the NIH, National Cancer Institute
FX This study was supported by the Intramural Research Program of the NIH,
National Cancer Institute.
NR 43
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U1 0
U2 4
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2458
J9 BMC PUBLIC HEALTH
JI BMC Public Health
PD OCT 27
PY 2014
VL 14
AR 1110
DI 10.1186/1471-2458-14-1110
PG 7
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA AU1AN
UT WOS:000345353500001
PM 25348940
ER
PT J
AU Li, Y
Lee, CY
Chen, RM
Zhou, QF
Shung, KK
AF Li, Ying
Lee, Changyang
Chen, Ruimin
Zhou, Qifa
Shung, K. Kirk
TI A feasibility study of in vivo applications of single beam acoustic
tweezers
SO APPLIED PHYSICS LETTERS
LA English
DT Article
ID ULTRASOUND MICROBEAM STIMULATION; CELLS; MANIPULATION
AB Tools that are capable of manipulating micro-sized objects have been widely used in such fields as physics, chemistry, biology, and medicine. Several devices, including optical tweezers, atomic force microscope, micro-pipette aspirator, and standing surface wave type acoustic tweezers have been studied to satisfy this need. However, none of them has been demonstrated to be suitable for in vivo and clinical studies. Single beam acoustic tweezers (SBAT) is a technology that uses highly focused acoustic beam to trap particles toward the beam focus. Its feasibility was first theoretically and experimentally demonstrated by Lee and Shung several years ago. Since then, much effort has been devoted to improving this technology. At present, the tool is capable of trapping a microparticle as small as 1 mu m, as well as a single red blood cell. Although in comparing to other microparticles manipulating technologies, SBAT has advantages of providing stronger trapping force and deeper penetration depth in tissues, and producing less tissue damage, its potential for in vivo applications has yet been explored. It is worth noting that ultrasound has been used as a diagnostic tool for over 50 years and no known major adverse effects have been observed at the diagnostic energy level. This paper reports the results of an initial attempt to assess the feasibility of single beam acoustic tweezers to trap microparticles in vivo inside of a blood vessel. The acoustic intensity of SBAT under the trapping conditions that were utilized was measured. The mechanical index and thermal index at the focus of acoustic beam were found to be 0.48 and 0.044, respectively, which meet the standard of commercial diagnostic ultrasound system. (C) 2014 AIP Publishing LLC.
C1 [Li, Ying] Univ So Calif, NIH Transducer Resource Ctr, Los Angeles, CA 90089 USA.
Univ So Calif, Dept Biomed Engn, Los Angeles, CA 90089 USA.
RP Li, Y (reprint author), Univ So Calif, NIH Transducer Resource Ctr, Los Angeles, CA 90089 USA.
EM yli582@usc.edu
OI Lee, Changyang/0000-0002-3746-7304
FU NIH [R01-EB12058, P41-EB02182]; Provost Postdoctoral Scholar Grant
FX This work has been supported by NIH Grant Nos. R01-EB12058 and
P41-EB02182 and a Provost Postdoctoral Scholar Grant. Special thanks to
Dr. Hong and Young-Kwon for providing the biological tissue sample for
this study.
NR 17
TC 4
Z9 5
U1 4
U2 20
PU AMER INST PHYSICS
PI MELVILLE
PA 1305 WALT WHITMAN RD, STE 300, MELVILLE, NY 11747-4501 USA
SN 0003-6951
EI 1077-3118
J9 APPL PHYS LETT
JI Appl. Phys. Lett.
PD OCT 27
PY 2014
VL 105
IS 17
AR 173701
DI 10.1063/1.4900716
PG 5
WC Physics, Applied
SC Physics
GA AS9WF
UT WOS:000344588600072
PM 25422525
ER
PT J
AU Wallander, JL
Biasini, FJ
Thorsten, V
Dhaded, SM
de Jong, DM
Chomba, E
Pasha, O
Goudar, S
Wallace, D
Chakraborty, H
Wright, LL
McClure, E
Carlo, WA
AF Wallander, Jan L.
Biasini, Fred J.
Thorsten, Vanessa
Dhaded, Sangappa M.
de Jong, Desiree M.
Chomba, Elwyn
Pasha, Omrana
Goudar, Shivaprasad
Wallace, Dennis
Chakraborty, Hrishikesh
Wright, Linda L.
McClure, Elizabeth
Carlo, Waldemar A.
TI Dose of early intervention treatment during children's first 36 months
of life is associated with developmental outcomes: an observational
cohort study in three low/low-middle income countries
SO BMC PEDIATRICS
LA English
DT Article
DE Treatment dose; Early developmental intervention; Neurodevelopmental
disability; Birth asphyxia; Developing countries
ID LOW-BIRTH-WEIGHT; HOME-BASED INTERVENTION; PREMATURE-INFANTS;
NUTRITIONAL SUPPLEMENTATION; PSYCHOSOCIAL STIMULATION;
INTELLECTUAL-DEVELOPMENT; PERINATAL-MORTALITY; DEVELOPMENT PROGRAM;
JAMAICAN CHILDREN; PARTICIPATION
AB Background: The positive effects of early developmental intervention (EDI) on early child development have been reported in numerous controlled trials in a variety of countries. An important aspect to determining the efficacy of EDI is the degree to which dosage is linked to outcomes. However, few studies of EDI have conducted such analyses. This observational cohort study examined the association between treatment dose and children's development when EDI was implemented in three low and low-middle income countries as well as demographic and child health factors associated with treatment dose.
Methods: Infants (78 males, 67 females) born in rural communities in India, Pakistan, and Zambia received a parent-implemented EDI delivered through biweekly home visits by trainers during the first 36 months of life. Outcome was measured at age 36 months with the Mental (MDI) and Psychomotor (PDI) Development Indices of the Bayley Scales of Infant Development-II. Treatment dose was measured by number of home visits completed and parent-reported implementation of assigned developmental stimulation activities between visits. Sociodemographic, prenatal, perinatal, and child health variables were measures as correlates.
Results: Average home visits dose exceeded 91% and mothers engaged the children in activities on average 62.5% of days. Higher home visits dose was significantly associated with higher MDI (mean for dose quintiles 1-2 combined = 97.8, quintiles 3-5 combined = 103.4, p = 0.0017). Higher treatment dose was also generally associated with greater mean PDI, but the relationships were non-linear. Location, sociodemographic, and child health variables were associated with treatment dose.
Conclusions: Receiving a higher dose of EDI during the first 36 months of life is generally associated with better developmental outcomes. The higher benefit appears when receiving >= 91% of biweekly home visits and program activities on >= 67% of days over 3 years. It is important to ensure that EDI is implemented with a sufficiently high dose to achieve desired effect. To this end groups at risk for receiving lower dose can be identified and may require special attention to ensure adequate effect.
C1 [Wallander, Jan L.] Univ Calif Merced, Psychol Sci & Hlth Sci Res Inst, Merced, CA 95343 USA.
[Biasini, Fred J.] Univ Alabama Birmingham, Sparks Clin, Birmingham, AL USA.
[Biasini, Fred J.] Univ Alabama Birmingham, Dept Psychol, Birmingham, AL 35294 USA.
[Thorsten, Vanessa; Wallace, Dennis; McClure, Elizabeth] RTI Int, Dept Stat & Epidemiol, Durham, NC USA.
[Dhaded, Sangappa M.; Goudar, Shivaprasad] KLE Jawaharlal Nehru Med Coll, Belgaum, India.
[de Jong, Desiree M.] Univ Massachusetts, Amherst, MA 01003 USA.
[Chomba, Elwyn] Univ Zambia, Lusaka, Zambia.
[Pasha, Omrana] Aga Kahn Univ, Coll Med, Karachi, Pakistan.
[Chakraborty, Hrishikesh] Univ S Carolina, Columbia, SC 29208 USA.
[Wright, Linda L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NICHD, Bethesda, MD USA.
[Carlo, Waldemar A.] Univ Alabama Birmingham, Dept Pediat, Birmingham, AL 35294 USA.
RP Wallander, JL (reprint author), Univ Calif Merced, Psychol Sci & Hlth Sci Res Inst, Merced, CA 95343 USA.
EM jwallander@ucmerced.edu
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development (NICHD); Global Network for Women's and Children's Health
Research [HD034216]; National Institute of Neurological Disorders and
Stroke; NICHD [HD43464, HD42372, HD40607, HD40636]; Fogarty
International Center [TW006703]; Children's of Alabama Centennial
Scholar Fund; Perinatal Health and Human Development Research Program;
Children's of Alabama Centennial Scholar Fund of the University of
Alabama at Birmingham
FX This research were funded in part by grants from the Eunice Kennedy
Shriver National Institute of Child Health and Human Development (NICHD)
Global Network for Women's and Children's Health Research (HD034216),
the National Institute of Neurological Disorders and Stroke and NICHD
(HD43464, HD42372, HD40607, and HD40636), the Fogarty International
Center (TW006703), the Children's of Alabama Centennial Scholar Fund,
and the Perinatal Health and Human Development Research Program and the
Children's of Alabama Centennial Scholar Fund of the University of
Alabama at Birmingham. The content is solely the responsibility of the
authors and does not necessarily represent the official views of the
National Institutes of Health (NIH); NIH staff contributed to the design
of the study and approved of the final manuscript, but had no influence
on the analysis and interpretation of the data or the decision to submit
the manuscript.
NR 38
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U1 1
U2 7
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2431
J9 BMC PEDIATR
JI BMC Pediatr.
PD OCT 25
PY 2014
VL 14
AR 281
DI 10.1186/1471-2431-14-281
PG 11
WC Pediatrics
SC Pediatrics
GA AW7KP
UT WOS:000346443300001
PM 25344731
ER
PT J
AU Matreyek, KA
Wang, WF
Serrao, E
Singh, PK
Levin, HL
Engelman, A
AF Matreyek, Kenneth A.
Wang, Weifeng
Serrao, Erik
Singh, Parmit Kumar
Levin, Henry L.
Engelman, Alan
TI Host and viral determinants for MxB restriction of HIV-1 infection
SO RETROVIROLOGY
LA English
DT Article
DE Innate immunity; MxB; Mx2; HIV-1; Restriction factor
ID HUMAN-IMMUNODEFICIENCY-VIRUS; TYPE-1 INTEGRASE MUTANTS; DYNAMIN-LIKE
MXA; DNA INTEGRATION; ANTIVIRAL SPECIFICITY; REVERSE TRANSCRIPTION;
QUANTITATIVE-ANALYSIS; NUCLEAR-ENVELOPE; EARLY STEPS; PROTEIN
AB Background: Interferon-induced cellular proteins play important roles in the host response against viral infection. The Mx family of dynamin-like GTPases, which include MxA and MxB, target a wide variety of viruses. Despite considerable evidence demonstrating the breadth of antiviral activity of MxA, human MxB was only recently discovered to specifically inhibit lentiviruses. Here we assess both host and viral determinants that underlie MxB restriction of HIV-1 infection.
Results: Heterologous expression of MxB in human osteosarcoma cells potently inhibited HIV-1 infection (similar to 12-fold), yet had little to no effect on divergent retroviruses. The anti-HIV effect manifested as a partial block in the formation of 2-long terminal repeat circle DNA and hence nuclear import, and we accordingly found evidence for an additional post-nuclear entry block. A large number of previously characterized capsid mutations, as well as mutations that abrogated integrase activity, counteracted MxB restriction. MxB expression suppressed integration into gene-enriched regions of chromosomes, similar to affects observed previously when cells were depleted for nuclear transport factors such as transportin 3. MxB activity did not require predicted GTPase active site residues or a series of unstructured loops within the stalk domain that confer functional oligomerization to related dynamin family proteins. In contrast, we observed an N-terminal stretch of residues in MxB to harbor key determinants. Protein localization conferred by a nuclear localization signal (NLS) within the N-terminal 25 residues, which was critical, was fully rescuable by a heterologous NLS. Consistent with this observation, a heterologous nuclear export sequence (NES) abolished full-length MxB activity. We additionally mapped sub-regions within amino acids 26-90 that contribute to MxB activity, finding sequences present within residues 27-50 particularly important.
Conclusions: MxB inhibits HIV-1 by interfering with minimally two steps of infection, nuclear entry and post-nuclear trafficking and/or integration, without destabilizing the inherent catalytic activity of viral preintegration complexes. Putative MxB GTPase active site residues and stalk domain Loop 4 -both previously shown to be necessary for MxA function - were dispensable for MxB antiviral activity. Instead, we highlight subcellular localization and a yet-determined function(s) present in the unique MxB N-terminal region to be required for HIV-1 restriction.
C1 [Matreyek, Kenneth A.; Wang, Weifeng; Serrao, Erik; Engelman, Alan] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA.
[Matreyek, Kenneth A.; Wang, Weifeng; Serrao, Erik; Engelman, Alan] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA.
[Singh, Parmit Kumar; Levin, Henry L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Eukaryot Transposable Elements, Program Cellular Regulat & Metab, NIH, Bethesda, MD 20892 USA.
RP Engelman, A (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St, Boston, MA 02115 USA.
EM alan_engelman@dfci.harvard.edu
OI Matreyek, Kenneth/0000-0001-9149-551X
FU US National Institute of Health (Harvard University Center for AIDS
Research) [AI052014, AI060354]; Eunice Kennedy Shriver National
Institute of Child Health and Human Development
FX We thank Tamaria Dewdney for comments on the manuscript, Frederic
Bushman and Nirav Malani for sharing integration sites obtained from
control and transportin 3 and RANBP2 knockdown cells, and Peter
Cherepanov for advice on bioinformatics analyses and critical reading of
the revised manuscript. This work was supported by US National Institute
of Health grants AI052014 (A.E.) and AI060354 (Harvard University Center
for AIDS Research) and by the Intramural Research Program of the NIH
from the Eunice Kennedy Shriver National Institute of Child Health and
Human Development (P.K.S. and H.L.L.).
NR 65
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U1 0
U2 3
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1742-4690
J9 RETROVIROLOGY
JI Retrovirology
PD OCT 25
PY 2014
VL 11
AR 90
DI 10.1186/s12977-014-0090-z
PG 20
WC Virology
SC Virology
GA AS9OC
UT WOS:000344570800001
PM 25348155
ER
PT J
AU Bellan, SE
Pulliam, JRC
Dushoff, J
Meyers, LA
AF Bellan, Steve E.
Pulliam, Juliet R. C.
Dushoff, Jonathan
Meyers, Lauren Ancel
TI Ebola control: effect of asymptomatic infection and acquired immunity
SO LANCET
LA English
DT Letter
ID VIRUS
C1 [Bellan, Steve E.] Univ Texas Austin, Ctr Computat Biol & Bioinformat, Austin, TX 78712 USA.
[Meyers, Lauren Ancel] Univ Texas Austin, Dept Integrat Biol, Austin, TX 78712 USA.
[Pulliam, Juliet R. C.] Univ Florida, Dept Biol, Gainesville, FL USA.
[Pulliam, Juliet R. C.] Univ Florida, Emerging Pathogens Inst, Gainesville, FL USA.
[Pulliam, Juliet R. C.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Dushoff, Jonathan] McMaster Univ, Dept Biol, Hamilton, ON, Canada.
[Dushoff, Jonathan] McMaster Univ, Inst Infect Dis Res, Hamilton, ON, Canada.
[Meyers, Lauren Ancel] Santa Fe Inst, Santa Fe, NM 87501 USA.
RP Bellan, SE (reprint author), Univ Texas Austin, Ctr Computat Biol & Bioinformat, Austin, TX 78712 USA.
EM steve.bellan@gmail.com
RI Pulliam, Juliet/A-6516-2008;
OI Pulliam, Juliet/0000-0003-3314-8223; Bellan, Steve/0000-0002-4110-272X
FU NIGMS NIH HHS [R25 GM102149, U01 GM087719]
NR 7
TC 26
Z9 30
U1 0
U2 21
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0140-6736
EI 1474-547X
J9 LANCET
JI Lancet
PD OCT 25
PY 2014
VL 384
IS 9953
BP 1499
EP 1500
DI 10.1016/S0140-6736(14)61839-0
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA AR9MO
UT WOS:000343899600015
PM 25390569
ER
PT J
AU Chen, BC
Legant, WR
Wang, K
Shao, L
Milkie, DE
Davidson, MW
Janetopoulos, C
Wu, XFS
Hammer, JA
Liu, Z
English, BP
Mimori-Kiyosue, Y
Romero, DP
Ritter, AT
Lippincott-Schwartz, J
Fritz-Laylin, L
Mullins, RD
Mitchell, DM
Bembenek, JN
Reymann, AC
Bohme, R
Grill, SW
Wang, JT
Seydoux, G
Tulu, US
Kiehart, DP
Betzig, E
AF Chen, Bi-Chang
Legant, Wesley R.
Wang, Kai
Shao, Lin
Milkie, Daniel E.
Davidson, Michael W.
Janetopoulos, Chris
Wu, Xufeng S.
Hammer, John A., III
Liu, Zhe
English, Brian P.
Mimori-Kiyosue, Yuko
Romero, Daniel P.
Ritter, Alex T.
Lippincott-Schwartz, Jennifer
Fritz-Laylin, Lillian
Mullins, R. Dyche
Mitchell, Diana M.
Bembenek, Joshua N.
Reymann, Anne-Cecile
Boehme, Ralph
Grill, Stephan W.
Wang, Jennifer T.
Seydoux, Geraldine
Tulu, U. Serdar
Kiehart, Daniel P.
Betzig, Eric
TI Lattice light-sheet microscopy: Imaging molecules to embryos at high
spatiotemporal resolution
SO SCIENCE
LA English
DT Article
ID PLANE ILLUMINATION MICROSCOPY; FLUORESCENCE MICROSCOPY; OPTICAL
LATTICES; ELEGANS EMBRYOS; CELL-MIGRATION; HIGH-SPEED; DYNAMICS;
TRACKING; SYSTEMS; PROTEIN
AB Although fluorescence microscopy provides a crucial window into the physiology of living specimens, many biological processes are too fragile, are too small, or occur too rapidly to see clearly with existing tools. We crafted ultrathin light sheets from two-dimensional optical lattices that allowed us to image three-dimensional (3D) dynamics for hundreds of volumes, often at subsecond intervals, at the diffraction limit and beyond. We applied this to systems spanning four orders of magnitude in space and time, including the diffusion of single transcription factor molecules in stem cell spheroids, the dynamic instability of mitotic microtubules, the immunological synapse, neutrophil motility in a 3D matrix, and embryogenesis in Caenorhabditis elegans and Drosophila melanogaster. The results provide a visceral reminder of the beauty and the complexity of living systems.
C1 [Chen, Bi-Chang; Legant, Wesley R.; Wang, Kai; Shao, Lin; Liu, Zhe; English, Brian P.; Betzig, Eric] Howard Hughes Med Inst, Ashburn, VA 20147 USA.
[Milkie, Daniel E.] Coleman Technol Inc, Newtown Sq, PA 19073 USA.
[Davidson, Michael W.] Florida State Univ, Natl High Magnet Field Lab, Tallahassee, FL 32310 USA.
[Davidson, Michael W.] Florida State Univ, Dept Biol Sci, Tallahassee, FL 32310 USA.
[Janetopoulos, Chris] Univ Sci, Dept Biol Sci, Philadelphia, PA 19104 USA.
[Wu, Xufeng S.; Hammer, John A., III] NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA.
[Mimori-Kiyosue, Yuko] RIKEN Ctr Dev Biol, Opt Image Anal Unit, Kobe, Hyogo 6500047, Japan.
[Romero, Daniel P.] Univ Minnesota, Dept Pharmacol, Minneapolis, MN 55455 USA.
[Ritter, Alex T.; Lippincott-Schwartz, Jennifer] NICHHD, Cell Biol & Metab Program, NIH, Bethesda, MD 20892 USA.
[Ritter, Alex T.] Addenbrookes Hosp, Cambridge Inst Med Res, Cambridge CB2 0XY, England.
[Fritz-Laylin, Lillian; Mullins, R. Dyche] Univ Calif San Francisco, Dept Cellular & Mol Pharmacol, San Francisco, CA 94158 USA.
[Mitchell, Diana M.; Bembenek, Joshua N.] Univ Tennessee, Dept Biochem & Cellular & Mol Biol, Knoxville, TN 37996 USA.
[Reymann, Anne-Cecile; Boehme, Ralph; Grill, Stephan W.] Max Planck Inst Mol Cell Biol & Genet, D-01307 Dresden, Germany.
[Reymann, Anne-Cecile; Boehme, Ralph; Grill, Stephan W.] Max Planck Inst Phys Komplexer Syst, D-01307 Dresden, Germany.
[Wang, Jennifer T.; Seydoux, Geraldine] Johns Hopkins Sch Med, Ctr Cell Dynam, Howard Hughes Med Inst, Dept Mol Biol & Genet, Baltimore, MD 21205 USA.
[Tulu, U. Serdar; Kiehart, Daniel P.] Duke Univ, Dept Biol, Durham, NC 27708 USA.
RP Betzig, E (reprint author), Howard Hughes Med Inst, Janelia Res Campus, Ashburn, VA 20147 USA.
EM betzige@janelia.hhmi.org
RI Chen , Bi-Chang /F-3480-2014; Mimori-Kiyosue, Yuko/K-9158-2015; English,
Brian/O-8156-2016; Grill, Stephan /D-9427-2012;
OI English, Brian/0000-0002-4037-6294; Wang, Jennifer/0000-0002-8506-5182;
Reymann, Anne-Cecile/0000-0002-0517-5083; Fritz-Laylin,
Lillian/0000-0002-9237-9403; Bembenek, Joshua/0000-0002-0966-2268;
Seydoux, Geraldine/0000-0001-8257-0493
FU Howard Hughes Medical Institute (HHMI); Janelia Visitor Program; NIH
[R01GM080370, RM01-GM61010, R01HD37047, GM033830]; Division of
Intramural Research, National Heart, Lung, and Blood Institute, NIH;
Japan Society for the Promotion of Science-NEXT program [LS128]; Uehara
Memorial Foundation; Takeda Science Foundation; Kurata Memorial Hitachi
Science and Technology Foundation; RIKEN Center for Developmental
Biology; HHMI; Human Frontier Science Program [LT000926/2012]; European
Research Council [281903]
FX We thank L. Gao, now at Stony Brook University, for technical expertise;
the Shared Resource teams at Janelia for their skill and dedication in
specimen handling and preparation; and the Instrument Design and
Fabrication team for their manufacturing expertise. B.-C.C., W.R.L.,
K.W., L.S., Z.L., B.P.E., and E.B. are funded by the Howard Hughes
Medical Institute (HHMI). We also gratefully acknowledge the support of
the Janelia Visitor Program. C.J. is supported by NIH grant R01GM080370.
X.S.W. and J.A.H. are funded by the Division of Intramural Research,
National Heart, Lung, and Blood Institute, NIH. Y.M.-K. is supported by
the Japan Society for the Promotion of Science-NEXT program LS128, the
Uehara Memorial Foundation, the Takeda Science Foundation, the Kurata
Memorial Hitachi Science and Technology Foundation, and an intramural
grant from the RIKEN Center for Developmental Biology. A.T.R. and J.L.S.
acknowledge G. M. Griffiths of the University of Cambridge as the
doctoral cosupervisor of A. T. R., who provided technical expertise with
CTL experiments. These experiments are a collaboration with GMG. L.F.L.
and R.D.M. were supported by NIH grant RM01-GM61010 and HHMI. A.-C. R.
is supported by the Human Frontier Science Program LT000926/2012. S.W.G.
acknowledges support from the European Research Council starting grant
281903. J.T.W. and G.S. are supported by NIH R01HD37047. G.S. is also an
HHMI Investigator. U.S.T. and D.P.K. are supported by NIH grant
GM033830. All data in the manuscript are available upon request.
Researchers can apply to access the microscope as visitors through the
Advanced Imaging Center at Janelia Farm (www.janelia.org/aic).
Documentation for the construction of a copy of the microscope is
available after execution of a research license with HHMI. Portions of
the technology described herein are covered by U.S. Patent 7,894,136
issued to E.B. and assigned to Lattice Light, LLC of Ashburn, VA; U.S.
Patent 8,711,211 issued to E.B. and assigned to HHMI; and U.S. Patent
application 13/844,405 filed by E.B. and K.W. and assigned to HHMI.
NR 58
TC 217
Z9 222
U1 39
U2 242
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 OCT 24
PY 2014
VL 346
IS 6208
BP 439
EP +
AR UNSP 1257998
DI 10.1126/science.1257998
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CB6YT
UT WOS:000349773700002
PM 25342811
ER
PT J
AU Dahal, RA
Pramod, AB
Sharma, B
Krout, D
Foster, JD
Cha, JH
Cao, JJ
Newman, AH
Lever, JR
Vaughan, RA
Henry, LK
AF Dahal, Rejwi Acharya
Pramod, Akula Bala
Sharma, Babita
Krout, Danielle
Foster, James D.
Cha, Joo Hwan
Cao, Jianjing
Newman, Amy Hauck
Lever, John R.
Vaughan, Roxanne A.
Henry, L. Keith
TI Computational and Biochemical Docking of the Irreversible Cocaine Analog
RTI 82 Directly Demonstrates Ligand Positioning in the Dopamine
Transporter Central Substrate-binding Site
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Review
DE Addiction; Dopamine Transporter; Molecular Docking; Molecular Dynamics;
Monoamine Transporter; Photoaffinity Labeling; SCAM; Topane
ID HUMAN SEROTONIN TRANSPORTERS; TRANSMEMBRANE DOMAIN-I; ACID
METHYL-ESTERS; NEUROTRANSMITTER TRANSPORTERS; MONOAMINE TRANSPORTERS;
MOLECULAR-DYNAMICS; CONFORMATIONAL-CHANGES; PHOTOAFFINITY LIGANDS;
IMPLICATES PROXIMITY; LEUCINE TRANSPORTER
AB Background: Cocaine interaction with DAT was assessed using the irreversible binding cocaine analog RTI 82. Results: Molecular modeling and peptide mapping identify adduction of RTI 82 to Phe-319 and Phe-320 of rat DAT and human DAT, respectively. Conclusion: Tropane-based pharmacophores bind to DAT in the central substrate site. Significance: Mapping the cocaine-binding site reveals new insights for medication discovery.
The dopamine transporter (DAT) functions as a key regulator of dopaminergic neurotransmission via re-uptake of synaptic dopamine (DA). Cocaine binding to DAT blocks this activity and elevates extracellular DA, leading to psychomotor stimulation and addiction, but the mechanisms by which cocaine interacts with DAT and inhibits transport remain incompletely understood. Here, we addressed these questions using computational and biochemical methodologies to localize the binding and adduction sites of the photoactivatable irreversible cocaine analog 3-(p-chlorophenyl)tropane-2-carboxylic acid, 4-azido-3-iodophenylethyl ester ([I-125]RTI 82). Comparative modeling and small molecule docking indicated that the tropane pharmacophore of RTI 82 was positioned in the central DA active site with an orientation that juxtaposed the aryliodoazide group for cross-linking to rat DAT Phe-319. This prediction was verified by focused methionine substitution of residues flanking this site followed by cyanogen bromide mapping of the [I-125]RTI 82-labeled mutants and by the substituted cysteine accessibility method protection analyses. These findings provide positive functional evidence linking tropane pharmacophore interaction with the core substrate-binding site and support a competitive mechanism for transport inhibition. This synergistic application of computational and biochemical methodologies overcomes many uncertainties inherent in other approaches and furnishes a schematic framework for elucidating the ligand-protein interactions of other classes of DA transport inhibitors.
C1 [Dahal, Rejwi Acharya; Pramod, Akula Bala; Sharma, Babita; Krout, Danielle; Foster, James D.; Vaughan, Roxanne A.; Henry, L. Keith] Univ N Dakota, Sch Med & Hlth Sci, Dept Basic Sci, Grand Forks, ND 58203 USA.
[Cha, Joo Hwan; Cao, Jianjing; Newman, Amy Hauck] NIDA, Med Chem Sect, Intramural Res Program, Baltimore, MD 21224 USA.
[Lever, John R.] Harry S Truman Mem Vet Hosp, Res Serv, Columbia, MO 65201 USA.
[Lever, John R.] Univ Missouri, Dept Radiol, Radiopharmaceut Sci Inst, Columbia, MO 65211 USA.
[Lever, John R.] Univ Missouri, Dept Med Pharmacol & Physiol, Columbia, MO 65211 USA.
RP Vaughan, RA (reprint author), 501 N Columbia Rd,Stop 9037, Grand Forks, ND 58202 USA.
EM roxanne.vaughan@med.und.edu; keith.henry@med.und.edu
FU National Institutes of Health Grants from the INBRE Program of the NCRR;
NIDA-Intramural Research Program; COBRE Program of the NCRR [DA027845,
P20 RR017699]; ND EPSCoR IIG [P20 RR016741]
FX This work was supported, in whole or in part, by National Institutes of
Health Grants from the INBRE Program of the NCRR and the NIDA-Intramural
Research Program (to A. H. N.), Grants DA027845 (to L. K. H. and R. A.
V.), P20 RR017699 (to University of North Dakota) from the COBRE Program
of the NCRR, and Grant P20 RR016741 from ND EPSCoR IIG (to R. A. V. and
J. D. F.).
NR 109
TC 11
Z9 11
U1 0
U2 18
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 OCT 24
PY 2014
VL 289
IS 43
BP 29712
EP 29727
DI 10.1074/jbc.M114.571521
PG 16
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA AS6JU
UT WOS:000344370800020
PM 25179220
ER
PT J
AU Liu, ZH
Li, WL
Ma, XF
Ding, N
Spallotta, F
Southon, E
Tessarollo, L
Gaetano, C
Mukouyama, YS
Thiele, CJ
AF Liu, Zhihui
Li, Wenling
Ma, Xuefei
Ding, Nancy
Spallotta, Francesco
Southon, Eileen
Tessarollo, Lino
Gaetano, Carlo
Mukouyama, Yoh-suke
Thiele, Carol J.
TI Essential Role of the Zinc Finger Transcription Factor Casz1 for
Mammalian Cardiac Morphogenesis and Development
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
DE Cardiac Development; Cardiovascular; Development; Heart Development;
Heart Failure
ID CONGENITAL HEART-DISEASE; DILATED CARDIOMYOPATHY; GENE-EXPRESSION;
CELL-CYCLE; MUTATIONS; CASTOR; DIFFERENTIATION; DROSOPHILA; GROWTH;
CYTOSKELETON
AB Background: The CASZ1 (castor zinc finger 1) gene localizes to chromosome 1p36, and 1p36 deletion syndrome is related to congenital heart disease (CHD). Results:Casz1 knock-out mice exhibited abnormal heart development and phenocopies aspects of 1p36 deletion syndrome related CHD. Conclusion:CASZ1 is critical for mammalian heart development. Significance:CASZ1 may be a novel CHD gene, and this finding opens new avenues for human heart disease diagnosis and treatment.
Chromosome 1p36 deletion syndrome is one of the most common terminal deletions observed in humans and is related to congenital heart disease (CHD). However, the 1p36 genes that contribute to heart disease have not been clearly delineated. Human CASZ1 gene localizes to 1p36 and encodes a zinc finger transcription factor. Casz1 is required for Xenopus heart ventral midline progenitor cell differentiation. Whether Casz1 plays a role during mammalian heart development is unknown. Our aim is to determine 1p36 gene CASZ1 function at regulating heart development in mammals. We generated a Casz1 knock-out mouse using Casz1-trapped embryonic stem cells. Casz1 deletion in mice resulted in abnormal heart development including hypoplasia of myocardium, ventricular septal defect, and disorganized morphology. Hypoplasia of myocardium was caused by decreased cardiomyocyte proliferation. Comparative genome-wide RNA transcriptome analysis of Casz1 depleted embryonic hearts identifies abnormal expression of genes that are critical for muscular system development and function, such as muscle contraction genes TNNI2, TNNT1, and CKM; contractile fiber gene ACTA1; and cardiac arrhythmia associated ion channel coding genes ABCC9 and CACNA1D. The transcriptional regulation of some of these genes by Casz1 was also found in cellular models. Our results showed that loss of Casz1 during mouse development led to heart defect including cardiac noncompaction and ventricular septal defect, which phenocopies 1p36 deletion syndrome related CHD. This suggests that CASZ1 is a novel 1p36 CHD gene and that the abnormal expression of cardiac morphogenesis and contraction genes induced by loss of Casz1 contributes to the heart defect.
C1 [Liu, Zhihui; Ding, Nancy; Thiele, Carol J.] NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA.
[Southon, Eileen; Tessarollo, Lino] NCI, Mouse Canc Genet Program, Neural Dev Sect, Bethesda, MD 20892 USA.
[Li, Wenling; Mukouyama, Yoh-suke] NHLBI, Lab Stem Cell & Neurovasc Biol, NIH, Bethesda, MD 20892 USA.
[Ma, Xuefei] NHLBI, Labs Mol Cardiol, NIH, Bethesda, MD 20892 USA.
[Spallotta, Francesco; Gaetano, Carlo] Goethe Univ Frankfurt, Div Cardiovasc Epigenet, Dept Cardiol, D-60596 Frankfurt, Germany.
RP Liu, ZH (reprint author), 9000 Rockville Pike,Bldg 10,Rm 1W-3940,MSC 1105, Bethesda, MD 20892 USA.
EM liuzhihu@mail.nih.gov; thielec@mail.nih.gov
OI Gaetano, Carlo/0000-0002-5238-1832
FU Intramural Research Program of the National Institutes of Health;
National Cancer Institute; Center for Cancer Research; LOEWE-CGT Centre
of Excellence; Wolfgang Geothe University; Deutsche
Forschungsgemeinschaft [SFB834]
FX This work was supported, in whole or in part, by the Intramural Research
Program of the National Institutes of Health, the National Cancer
Institute, and the Center for Cancer Research.; Supported by the
LOEWE-CGT Centre of Excellence, Wolfgang Geothe University, and by
Deutsche Forschungsgemeinschaft Program SFB834, "Endothelial Signaling
and Vascular Repair," Project B11 (to C.G.).
NR 61
TC 16
Z9 18
U1 0
U2 4
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
EI 1083-351X
J9 J BIOL CHEM
JI J. Biol. Chem.
PD OCT 24
PY 2014
VL 289
IS 43
BP 29801
EP 29816
DI 10.1074/jbc.M114.570416
PG 16
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA AS6JU
UT WOS:000344370800026
PM 25190801
ER
PT J
AU Bharti, SK
Sommers, JA
Zhou, J
Kaplan, DL
Spelbrink, JN
Mergny, JL
Brosh, RM
AF Bharti, Sanjay Kumar
Sommers, Joshua A.
Zhou, Jun
Kaplan, Daniel L.
Spelbrink, Johannes N.
Mergny, Jean-Louis
Brosh, Robert M., Jr.
TI DNA Sequences Proximal to Human Mitochondrial DNA Deletion Breakpoints
Prevalent in Human Disease Form G-quadruplexes, a Class of DNA
Structures Inefficiently Unwound by the Mitochondrial Replicative
Twinkle Helicase
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Review
DE DNA Helicase; DNA Replication; G-quadruplex; Genetic Disease; Genomic
Instability; Mitochondria; Twinkle
ID KEARNS-SAYRE SYNDROME; PROGRESSIVE EXTERNAL OPHTHALMOPLEGIA;
SUBSTANTIA-NIGRA NEURONS; MARROW-PANCREAS SYNDROME; LARGE-SCALE
DELETIONS; SACCHAROMYCES-CEREVISIAE; DIRECT REPEATS; HOMOLOGOUS
RECOMBINATION; GENOMIC STABILITY; PARKINSON-DISEASE
AB Background: Mitochondrial DNA deletions are prominent in human genetic disorders and cancer. Results: Predicted mitochondrial G-quadruplex-forming sequences map in close proximity to known deletion breakpoints and form G-quadruplexes in vitro. Conclusion: The mitochondrial replicative helicase Twinkle inefficiently unwinds intra- and intermolecular G-quadruplexes. Significance: Mitochondrial G-quadruplexes are likely to cause genome instability by perturbing replication machinery.
Mitochondrial DNA deletions are prominent in human genetic disorders, cancer, and aging. It is thought that stalling of the mitochondrial replication machinery during DNA synthesis is a prominent source of mitochondrial genome instability; however, the precise molecular determinants of defective mitochondrial replication are not well understood. In this work, we performed a computational analysis of the human mitochondrial genome using the Pattern Finder G-quadruplex (G4) predictor algorithm to assess whether G4-forming sequences reside in close proximity (within 20 base pairs) to known mitochondrial DNA deletion breakpoints. We then used this information to map G4P sequences with deletions characteristic of representative mitochondrial genetic disorders and also those identified in various cancers and aging. Circular dichroism and UV spectral analysis demonstrated that mitochondrial G-rich sequences near deletion breakpoints prevalent in human disease form G-quadruplex DNA structures. A biochemical analysis of purified recombinant human Twinkle protein (gene product of c10orf2) showed that the mitochondrial replicative helicase inefficiently unwinds well characterized intermolecular and intramolecular G-quadruplex DNA substrates, as well as a unimolecular G4 substrate derived from a mitochondrial sequence that nests a deletion breakpoint described in human renal cell carcinoma. Although G4 has been implicated in the initiation of mitochondrial DNA replication, our current findings suggest that mitochondrial G-quadruplexes are also likely to be a source of instability for the mitochondrial genome by perturbing the normal progression of the mitochondrial replication machinery, including DNA unwinding by Twinkle helicase.
C1 [Bharti, Sanjay Kumar; Sommers, Joshua A.; Brosh, Robert M., Jr.] NIA, Lab Mol Gerontol, NIH, Biomed Res Ctr, Baltimore, MD 21224 USA.
[Zhou, Jun; Mergny, Jean-Louis] Univ Bordeaux 2, ARNA Lab, F-33000 Bordeaux, France.
[Zhou, Jun; Mergny, Jean-Louis] IECB, INSERM U869, F-33600 Pessac, France.
[Kaplan, Daniel L.] Florida State Univ, Coll Med, Dept Biomed Sci, Tallahassee, FL 32312 USA.
[Spelbrink, Johannes N.] Univ Tampere, Pirkanmaa Hosp Dist, BioMediTech, FinMIT Ctr Excellence, FI-33014 Tampere, Finland.
[Spelbrink, Johannes N.] Univ Tampere, Pirkanmaa Hosp Dist, Tampere Univ Hosp, FI-33014 Tampere, Finland.
[Spelbrink, Johannes N.] Radboud Univ Nijmegen, Med Ctr, Nijmegan Ctr Mitochondrial Disorders, Dept Pediat, NL-6500 HB Nijmegen, Netherlands.
RP Brosh, RM (reprint author), NIA, Lab Mol Gerontol, NIH, Biomed Res Ctr, 251 Bayview Blvd, Baltimore, MD 21224 USA.
EM broshr@mail.nih.gov
RI Spelbrink, Johannes/L-4661-2015; ZHOU, JUN/N-2892-2014; Mergny,
Jean-Louis/E-2860-2013;
OI Spelbrink, Johannes/0000-0002-9756-2602; ZHOU, JUN/0000-0002-6793-3169;
Mergny, Jean-Louis/0000-0003-3043-8401; Kaplan,
Daniel/0000-0003-2760-7745
FU National Institutes of Health, NIA; European Union; Academy of Finland
(Centre of Excellence funding); Netherlands Organization for Scientific
Research (NWO), VICI Grant [865.10.004]; Fondation ARC; Aquitaine
Regional Council; Agence Nationale de la Recherche (ANR)
FX This research was supported, in whole or in part, by the National
Institutes of Health, NIA, Intramural Research Program.; Recipient of a
European Union Marie Curie International Incoming Fellowship (IIF).;
Supported by the Academy of Finland (Centre of Excellence funding) and
the Netherlands Organization for Scientific Research (NWO), VICI Grant
865.10.004.; Supported by Fondation ARC, the Aquitaine Regional Council,
and the Agence Nationale de la Recherche (ANR Grants Quarpdiem and
Oligoswitch).
NR 102
TC 17
Z9 18
U1 1
U2 17
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 OCT 24
PY 2014
VL 289
IS 43
BP 29975
EP 29993
DI 10.1074/jbc.M114.567073
PG 19
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA AS6JU
UT WOS:000344370800039
PM 25193669
ER
PT J
AU Kumar, NP
Sridhar, R
Hanna, LE
Banurekha, VV
Nutman, TB
Babu, S
AF Kumar, Nathella Pavan
Sridhar, Rathinam
Hanna, Luke E.
Banurekha, Vaithilingam V.
Nutman, Thomas B.
Babu, Subash
TI Decreased Frequencies of Circulating CD4(+) T Follicular Helper Cells
Associated with Diminished Plasma IL-21 in Active Pulmonary Tuberculosis
SO PLOS ONE
LA English
DT Article
ID FH CELLS
AB Background: Circulating T follicular helper (Tfh) cells represent a distinct subset of CD4(+) T cells and are important in immunity to infections. Although they have been shown to play a role in experimental models of tuberculosis infection, their role in human tuberculosis remains unexplored.
Aims/Methodology: To determine the distribution of circulating Tfh cells in human TB, we measured the frequencies of Tfh cells ex vivo and following TB - antigen or polyclonal stimulation in pulmonary TB (PTB; n = 30) and latent TB (LTB; n = 20) individuals, using the markers CXCR5, PD-1 and ICOS.
Results: We found that both ex vivo and TB - antigen induced frequencies of Tfh cell subsets was significantly lower in PTB compared to LTB individuals. Similarly, antigen induced frequencies of Tfh cells expressing IL-21 was also significantly lower in PTB individuals and this was reflected in diminished circulating levels of IL-21 and IFN gamma. This was not accompanied by diminished frequencies of activated or memory B cell subsets. Finally, the diminution in frequency of Tfh cells in PTB individuals was dependent on IL-10, CTLA-4 and PD-L1 in vitro.
Conclusions: Thus, PTB is characterized by adiminution in the frequency of Tfh cell subsets.
C1 [Kumar, Nathella Pavan; Babu, Subash] Int Ctr Excellence Res, Natl Inst Hlth, Madras, Tamil Nadu, India.
[Kumar, Nathella Pavan; Hanna, Luke E.; Banurekha, Vaithilingam V.] Natl Inst Res TB, Madras, Tamil Nadu, India.
[Sridhar, Rathinam] Govt Stanley Med Hosp, Madras, Tamil Nadu, India.
[Nutman, Thomas B.; Babu, Subash] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Babu, S (reprint author), Int Ctr Excellence Res, Natl Inst Hlth, Madras, Tamil Nadu, India.
EM sbabu@mail.nih.gov
FU Division of Intramural Research, NIAID, NIH
FX This study was funded by the Division of Intramural Research, NIAID,
NIH. The funders had no role in study design, data collection and
analysis, decision to publish or preparation of the manuscript.
NR 21
TC 7
Z9 7
U1 0
U2 4
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD OCT 24
PY 2014
VL 9
IS 10
AR e111098
DI 10.1371/journal.pone.0111098
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AS0BL
UT WOS:000343943500079
PM 25343703
ER
PT J
AU Pak, Y
Pastan, I
Kreitman, RJ
Lee, B
AF Pak, Youngshang
Pastan, Ira
Kreitman, Robert J.
Lee, Byungkook
TI Effect of Antigen Shedding on Targeted Delivery of Immunotoxins in Solid
Tumors from a Mathematical Model
SO PLOS ONE
LA English
DT Article
ID RECOMBINANT IMMUNOTOXIN; ANTITUMOR-ACTIVITY; ANIMAL TOXICITY; CANCER;
CELL; MESOTHELIN; THERAPY; PENETRATION; BINDING; IMMUNOTHERAPY
AB Most cancer-specific antigens used as targets of antibody-drug conjugates and immunotoxins are shed from the cell surface (Zhang & Pastan (2008) Clin. Cancer Res. 14: 7981-7986), although at widely varying rates and by different mechanisms (Dello Sbarba & Rovida (2002) Biol. Chem. 383: 69-83). Why many cancer-specific antigens are shed and how the shedding affects delivery efficiency of antibody-based protein drugs are poorly understood questions at present. Before a detailed numerical study, it was assumed that antigen shedding would reduce the efficacy of antibody-drug conjugates and immunotoxins. However, our previous study using a comprehensive mathematical model showed that antigen shedding can significantly improve the efficacy of the mesothelin-binding immunotoxin, SS1P (anti-mesothelin-Fv-PE38), and suggested that receptor shedding can be a general mechanism for enhancing the effect of inter-cellular signaling molecules. Here, we improved this model and applied it to both SS1P and another recombinant immunotoxin, LMB-2, which targets CD25. We show that the effect of antigen shedding is influenced by a number of factors including the number of antigen molecules on the cell surface and the endocytosis rate. The high shedding rate of mesothelin is beneficial for SS1P, for which the antigen is large in number and endocytosed rapidly. On the other hand, the slow shedding of CD25 is beneficial for LMB-2, for which the antigen is small in number and endocytosed slowly.
C1 [Pak, Youngshang] Pusan Natl Univ, Dept Chem, Pusan, South Korea.
[Pak, Youngshang] Pusan Natl Univ, Inst Funct Mat, Pusan, South Korea.
[Pak, Youngshang; Pastan, Ira; Kreitman, Robert J.; Lee, Byungkook] NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Pak, Y (reprint author), Pusan Natl Univ, Dept Chem, Pusan, South Korea.
EM ypak@pusan.ac.kr; bk@nih.gov
FU NCI; Intramural Research Program of the NIH, National Cancer Institute,
Center for Cancer Research
FX This work was supported in part by an appointment to the ORISE Research
Participation Program at NCI. This program is administered by the Oak
Ridge Institute for Science and Education through an interagency
agreement between the US department of Energy and the National Cancer
Institute. This research was supported by the Intramural Research
Program of the NIH, National Cancer Institute, Center for Cancer
Research. The funders had no role in study design, data collection and
analysis, decision to publish, or preparation of the manuscript.
NR 35
TC 4
Z9 4
U1 1
U2 10
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD OCT 24
PY 2014
VL 9
IS 10
AR e110716
DI 10.1371/journal.pone.0110716
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AS0BL
UT WOS:000343943500051
PM 25343405
ER
PT J
AU Cogle, CR
Wise, E
Meacham, AM
Zierold, C
Traverse, JH
Henry, TD
Perin, EC
Willerson, JT
Ellis, SG
Carlson, M
Zhao, DXM
Bolli, R
Cooke, JP
Anwaruddin, S
Bhatnagar, A
Cabreira-Hansen, MD
Grant, MB
Lai, DJ
Moye, L
Ebert, RF
Olson, RE
Sayre, SL
Schulman, IH
Bosse, RC
Scott, EW
Simari, RD
Pepine, CJ
Taylor, DA
AF Cogle, Christopher R.
Wise, Elizabeth
Meacham, Amy M.
Zierold, Claudia
Traverse, Jay H.
Henry, Timothy D.
Perin, Emerson C.
Willerson, James T.
Ellis, Stephen G.
Carlson, Marjorie
Zhao, David X. M.
Bolli, Roberto
Cooke, John P.
Anwaruddin, Saif
Bhatnagar, Aruni
Cabreira-Hansen, Maria da Graca
Grant, Maria B.
Lai, Dejian
Moye, Lem
Ebert, Ray F.
Olson, Rachel E.
Sayre, Shelly L.
Schulman, Ivonne H.
Bosse, Raphael C.
Scott, Edward W.
Simari, Robert D.
Pepine, Carl J.
Taylor, Doris A.
CA CCTRN
TI Detailed Analysis of Bone Marrow From Patients With Ischemic Heart
Disease and Left Ventricular Dysfunction BM CD34, CD11b, and Clonogenic
Capacity as Biomarkers for Clinical Outcomes
SO CIRCULATION RESEARCH
LA English
DT Article
DE angiogenesis effect; blood cells; bone marrow; myocardial infarction;
stem cells
ID ACUTE MYOCARDIAL-INFARCTION; COLONY-FORMING CELLS; MONONUCLEAR-CELLS;
TRANSENDOCARDIAL DELIVERY; INTRACTABLE ANGINA; PERIPHERAL-BLOOD;
MONOCYTE SUBSETS; RANDOMIZED-TRIAL; STEM-CELLS; THERAPY
AB Rationale: Bone marrow (BM) cell therapy for ischemic heart disease (IHD) has shown mixed results. Before the full potency of BM cell therapy can be realized, it is essential to understand the BM niche after acute myocardial infarction (AMI).
Objective: To study the BM composition in patients with IHD and severe left ventricular (LV) dysfunction.
Methods and Results: BM from 280 patients with IHD and LV dysfunction were analyzed for cell subsets by flow cytometry and colony assays. BM CD34(+) cell percentage was decreased 7 days after AMI (mean of 1.9% versus 2.3%-2.7% in other cohorts; P<0.05). BM-derived endothelial colonies were significantly decreased (P<0.05). Increased BM CD11b(+) cells associated with worse LV ejection fraction (LVEF) after AMI (P<0.05). Increased BM CD34(+) percentage associated with greater improvement in LVEF (+9.9% versus +2.3%; P=0.03, for patients with AMI and +6.6% versus -0.02%; P=0.021 for patients with chronic IHD). In addition, decreased BM CD34(+) percentage in patients with chronic IHD correlated with decrement in LVEF (-2.9% versus +0.7%; P=0.0355).
Conclusions: In this study, we show a heterogeneous mixture of BM cell subsets, decreased endothelial colony capacity, a CD34+ cell nadir 7 days after AMI, a negative correlation between CD11b percentage and postinfarct LVEF, and positive correlation of CD34 percentage with change in LVEF after cell therapy. These results serve as a possible basis for the small clinical improvement seen in autologous BM cell therapy trials and support selection of potent cell subsets and reversal of comorbid BM impairment.
C1 [Cogle, Christopher R.; Wise, Elizabeth; Meacham, Amy M.; Grant, Maria B.; Bosse, Raphael C.; Scott, Edward W.; Pepine, Carl J.] Univ Florida, Coll Med, Gainesville, FL USA.
[Zierold, Claudia; Carlson, Marjorie] Univ Minnesota, Sch Med, Minneapolis, MN 55455 USA.
[Traverse, Jay H.; Henry, Timothy D.; Olson, Rachel E.] Minneapolis Heart Inst Fdn Abbott, Minneapolis, MN USA.
[Perin, Emerson C.; Willerson, James T.; Cabreira-Hansen, Maria da Graca; Taylor, Doris A.] Texas Heart Inst, Houston, TX 77025 USA.
[Ellis, Stephen G.] Cleveland Clin Fdn, Cleveland, OH 44195 USA.
[Zhao, David X. M.] Wake Forest Baptist Hlth, Winston Salem, NC USA.
[Bolli, Roberto; Bhatnagar, Aruni] Univ Louisville, Sch Med, Louisville, KY 40292 USA.
[Cooke, John P.] Houston Methodist Res Inst, Houston, TX USA.
[Anwaruddin, Saif] Univ Penn, Sch Med, Philadelphia, PA 19104 USA.
[Lai, Dejian; Moye, Lem; Sayre, Shelly L.] Univ Texas Sch Publ Hlth, Houston, TX 77030 USA.
[Ebert, Ray F.] NHLBI, Bethesda, MD 20892 USA.
[Schulman, Ivonne H.] Univ Miami, Sch Med, Coral Gables, FL 33124 USA.
[Simari, Robert D.] Mayo Clin, Coll Med, Rochester, MN USA.
RP Moye, L (reprint author), Univ Texas Sch Publ Hlth, 1200 Herman Pressler,E-1009, Houston, TX 77030 USA.
EM LemMoye@msn.com
RI Cogle, Christopher/H-1746-2016;
OI Cogle, Christopher/0000-0001-5422-6863; Cooke, John/0000-0003-0033-9138
FU National Institutes of Health (NIH) network grants (National Heart,
Lung, and Blood Institute [NHLBI]) [UM1 HL087318-08]; NIH R01 [NHLBI R01
HL091005]
FX This study was supported by National Institutes of Health (NIH) network
grants (National Heart, Lung, and Blood Institute [NHLBI] UM1
HL087318-08); NIH R01 to Pepine and Cogle (NHLBI R01 HL091005).
NR 29
TC 25
Z9 25
U1 0
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7330
EI 1524-4571
J9 CIRC RES
JI Circ.Res.
PD OCT 24
PY 2014
VL 115
IS 10
BP 867
EP U152
DI 10.1161/CIRCRESAHA.115.304353
PG 10
WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular
Disease
SC Cardiovascular System & Cardiology; Hematology
GA AR7MB
UT WOS:000343762700012
PM 25136078
ER
PT J
AU Glessner, JT
Bick, AG
Ito, K
Homsy, JG
Rodriguez-Murillo, L
Fromer, M
Mazaika, E
Vardarajan, B
Italia, M
Leipzig, J
DePalma, SR
Golhar, R
Sanders, SJ
Yamrom, B
Ronemus, M
Iossifov, I
Willsey, AJ
State, MW
Kaltman, JR
White, PS
Shen, YF
Warburton, D
Brueckner, M
Seidman, C
Goldmuntz, E
Gelb, BD
Lifton, R
Seidman, J
Hakonarson, H
Chung, WK
AF Glessner, Joseph T.
Bick, Alexander G.
Ito, Kaoru
Homsy, Jason G.
Rodriguez-Murillo, Laura
Fromer, Menachem
Mazaika, Erica
Vardarajan, Badri
Italia, Michael
Leipzig, Jeremy
DePalma, Steven R.
Golhar, Ryan
Sanders, Stephan J.
Yamrom, Boris
Ronemus, Michael
Iossifov, Ivan
Willsey, A. Jeremy
State, Matthew W.
Kaltman, Jonathan R.
White, Peter S.
Shen, Yufeng
Warburton, Dorothy
Brueckner, Martina
Seidman, Christine
Goldmuntz, Elizabeth
Gelb, Bruce D.
Lifton, Richard
Seidman, Jonathan
Hakonarson, Hakon
Chung, Wendy K.
TI Increased Frequency of De Novo Copy Number Variants in Congenital Heart
Disease by Integrative Analysis of Single Nucleotide Polymorphism Array
and Exome Sequence Data
SO CIRCULATION RESEARCH
LA English
DT Article
DE DNA copy number variations; genomics; microarray analysis; polymorphism,
single nucleotide
ID HIDDEN-MARKOV MODEL; SNP GENOTYPING DATA; TGF-BETA RECEPTOR; LARGE GENE
LISTS; TRANSCRIPTION FACTORS; CONOTRUNCAL DEFECTS; CHROMOSOME 1Q21.1;
SEPTAL-DEFECTS; DELETION; MUTATIONS
AB Rationale: Congenital heart disease (CHD) is among the most common birth defects. Most cases are of unknown pathogenesis.
Objective: To determine the contribution of de novo copy number variants (CNVs) in the pathogenesis of sporadic CHD.
Methods and Results: We studied 538 CHD trios using genome-wide dense single nucleotide polymorphism arrays and whole exome sequencing. Results were experimentally validated using digital droplet polymerase chain reaction. We compared validated CNVs in CHD cases with CNVs in 1301 healthy control trios. The 2 complementary high-resolution technologies identified 63 validated de novo CNVs in 51 CHD cases. A significant increase in CNV burden was observed when comparing CHD trios with healthy trios, using either single nucleotide polymorphism array (P=7x10(-5); odds ratio, 4.6) or whole exome sequencing data (P=6x10(-4); odds ratio, 3.5) and remained after removing 16% of de novo CNV loci previously reported as pathogenic (P=0.02; odds ratio, 2.7). We observed recurrent de novo CNVs on 15q11.2 encompassing CYFIP1, NIPA1, and NIPA2 and single de novo CNVs encompassing DUSP1, JUN, JUP, MED15, MED9, PTPRE SREBF1, TOP2A, and ZEB2, genes that interact with established CHD proteins NKX2-5 and GATA4. Integrating de novo variants in whole exome sequencing and CNV data suggests that ETS1 is the pathogenic gene altered by 11q24.2-q25 deletions in Jacobsen syndrome and that CTBP2 is the pathogenic gene in 10q subtelomeric deletions.
Conclusions: We demonstrate a significantly increased frequency of rare de novo CNVs in CHD patients compared with healthy controls and suggest several novel genetic loci for CHD.
C1 [Glessner, Joseph T.; Golhar, Ryan; Hakonarson, Hakon] Childrens Hosp Philadelphia, Ctr Appl Genom, Philadelphia, PA 19104 USA.
[Italia, Michael; Leipzig, Jeremy; White, Peter S.] Childrens Hosp Philadelphia, Ctr Biomed Informat, Philadelphia, PA 19104 USA.
[Goldmuntz, Elizabeth] Childrens Hosp Philadelphia, Div Cardiol, Philadelphia, PA 19104 USA.
[Glessner, Joseph T.; Hakonarson, Hakon] Univ Penn, Dept Pediat, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Bick, Alexander G.; Ito, Kaoru; Homsy, Jason G.; Mazaika, Erica; DePalma, Steven R.; Seidman, Christine; Seidman, Jonathan] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA.
[Homsy, Jason G.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.
[Rodriguez-Murillo, Laura; Gelb, Bruce D.] Icahn Sch Med Mt Sinai, Dept Pediat, Mindich Child Hlth & Dev Inst, New York, NY 10029 USA.
[Rodriguez-Murillo, Laura; Fromer, Menachem; Gelb, Bruce D.] Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, New York, NY 10029 USA.
[Fromer, Menachem] Icahn Sch Med Mt Sinai, Icahn Inst Genom & Multiscale Biol, New York, NY 10029 USA.
[Fromer, Menachem] Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA.
[Vardarajan, Badri; Shen, Yufeng] Columbia Univ, Med Ctr, Dept Syst Biol, New York, NY 10032 USA.
[Warburton, Dorothy] Columbia Univ, Med Ctr, Dept Genet & Dev Med, New York, NY 10032 USA.
[Chung, Wendy K.] Columbia Univ, Med Ctr, Dept Pediat & Med, New York, NY 10032 USA.
[Sanders, Stephan J.; Willsey, A. Jeremy; State, Matthew W.; Lifton, Richard] Yale Univ, Dept Genet, New Haven, CT USA.
[Brueckner, Martina] Yale Univ, Dept Pediat, New Haven, CT 06520 USA.
[Lifton, Richard] Yale Univ, Dept Med, New Haven, CT 06520 USA.
[Sanders, Stephan J.; Willsey, A. Jeremy; State, Matthew W.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA.
[Yamrom, Boris; Ronemus, Michael; Iossifov, Ivan] Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA.
[Kaltman, Jonathan R.] NHLBI, Dept Cardiovasc Sci, NIH, Bethesda, MD 20892 USA.
RP Hakonarson, H (reprint author), Univ Penn, Dept Pediat, Ctr Appl Genom, Philadelphia, PA 19104 USA.
EM hakonarson@email.chop.edu; Wkc15@Cumc.Columbia.Edu
OI Leipzig, Jeremy/0000-0001-7224-9620; Sanders,
Stephan/0000-0001-9112-5148
FU National Institutes of Health (NIH) National Heart, Lung, and Blood
Institute (NHLBI) Pediatric Cardiac Genomics Consortium [U01-HL098188,
U01-HL098147, U01-HL098153, U01-HL098163, U01-HL098123, U01-HL098162];
Simons Foundation for Autism Research; NIH Centers for Mendelian
Genomics [5U54HG006504]; John S. LaDue Fellowship of Harvard Medical
School
FX This work was supported by the National Institutes of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI) Pediatric Cardiac
Genomics Consortium (U01-HL098188, U01-HL098147, U01-HL098153,
U01-HL098163, U01-HL098123, and U01-HL098162) and in part by the Simons
Foundation for Autism Research and the NIH Centers for Mendelian
Genomics (5U54HG006504). J.G. Homsy is supported by the John S. LaDue
Fellowship of Harvard Medical School.
NR 71
TC 40
Z9 43
U1 1
U2 16
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7330
EI 1524-4571
J9 CIRC RES
JI Circ.Res.
PD OCT 24
PY 2014
VL 115
IS 10
BP 884
EP U209
DI 10.1161/CIRCRESAHA.115.304458
PG 46
WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular
Disease
SC Cardiovascular System & Cardiology; Hematology
GA AR7MB
UT WOS:000343762700014
PM 25205790
ER
PT J
AU Misasi, J
Sullivan, NJ
AF Misasi, John
Sullivan, Nancy J.
TI Camouflage and Misdirection: The Full-On Assault of Ebola Virus Disease
SO CELL
LA English
DT Review
ID INTERFERON INHIBITORY DOMAIN; DOUBLE-STRANDED-RNA; VESICULAR
STOMATITIS-VIRUS; INNATE IMMUNE-RESPONSE; NIEMANN-PICK C1; VP35 PROTEIN;
DC-SIGN; HEMORRHAGIC-FEVER; ZAIRE-EBOLAVIRUS; ENTRY REQUIRES
AB Ebolaviruses cause a severe hemorrhagic fever syndrome that is rapidly fatal to humans and nonhuman primates. Ebola protein interactions with host cellular proteins disrupt type I and type II interferon responses, RNAi antiviral responses, antigen presentation, T-cell-dependent B cell responses, humoral antibodies, and cell-mediated immunity. This multifaceted approach to evasion and suppression of innate and adaptive immune responses in their target hosts leads to the severe immune dysregulation and "cytokine storm" that is characteristic of fatal ebolavirus infection. Here, we highlight some of the processes by which Ebola interacts with its mammalian hosts to evade antiviral defenses.
C1 [Misasi, John] Boston Childrens Hosp, Dept Med, Div Infect Dis, Boston, MA 02115 USA.
[Sullivan, Nancy J.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
RP Sullivan, NJ (reprint author), NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
EM njsull@mail.nih.gov
FU US NIH NIAID Vaccine Research Center, NIH [K08-AI079381]; Boston
Children's Hospital Faculty Development Fellowship
FX The authors thank B. Hartman for graphics and A. Tislerics for editing
the manuscript. This work was supported by the Intramural Research
Program of the US NIH NIAID Vaccine Research Center, NIH grant
K08-AI079381, and a Boston Children's Hospital Faculty Development
Fellowship.
NR 117
TC 20
Z9 24
U1 3
U2 75
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0092-8674
EI 1097-4172
J9 CELL
JI Cell
PD OCT 23
PY 2014
VL 159
IS 3
BP 477
EP 486
DI 10.1016/j.cell.2014.10.006
PG 10
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA AS8TU
UT WOS:000344521700006
PM 25417101
ER
PT J
AU Okabe, K
Kobayashi, S
Yamada, T
Kurihara, T
Tai-Nagara, I
Miyamoto, T
Mukouyama, YS
Sato, TN
Suda, T
Ema, M
Kubota, Y
AF Okabe, Keisuke
Kobayashi, Sakiko
Yamada, Toru
Kurihara, Toshihide
Tai-Nagara, Ikue
Miyamoto, Takeshi
Mukouyama, Yoh-suke
Sato, Thomas N.
Suda, Toshio
Ema, Masatsugu
Kubota, Yoshiaki
TI Neurons Limit Angiogenesis by Titrating VEGF in Retina
SO CELL
LA English
DT Article
ID BAC TG MICE; PROGENITOR CELLS; VASCULAR DEVELOPMENT; ENDOTHELIAL-CELLS;
GROWTH; MOUSE; MORPHOGENESIS; RECEPTOR; EXPRESSION; SURVIVAL
AB Vascular and nervous systems, two major networks in mammalian bodies, show a high degree of anatomical parallelism and functional crosstalk. During development, neurons guide and attract blood vessels, and consequently this parallelism is established. Here, we identified a noncanonical neurovascular interaction in eye development and disease. VEGFR2, a critical endothelial receptor for VEGF, was more abundantly expressed in retinal neurons than in endothelial cells, including endothelial tip cells. Genetic deletion of VEGFR2 in neurons caused misdirected angiogenesis toward neurons, resulting in abnormally increased vascular density around neurons. Further genetic experiments revealed that this misdirected angiogenesis was attributable to an excessive amount of VEGF protein around neurons caused by insufficient engulfment of VEGF by VEGFR2-deficient neurons. Moreover, absence of neuronal VEGFR2 caused misdirected regenerative angiogenesis in ischemic retinopathy. Thus, this study revealed neurovascular crosstalk and unprecedented cellular regulation of VEGF: retinal neurons titrate VEGF to limit neuronal vascularization.
C1 [Okabe, Keisuke; Kobayashi, Sakiko; Yamada, Toru; Tai-Nagara, Ikue; Kubota, Yoshiaki] Keio Univ, Sch Med, Lab Vasc Biol, Shinjuku Ku, Tokyo 1608582, Japan.
[Okabe, Keisuke] Keio Univ, Sch Med, Dept Plast Surg, Shinjuku Ku, Tokyo 1608582, Japan.
[Yamada, Toru] Keio Univ, Sch Med, Dept Surg, Shinjuku Ku, Tokyo 1608582, Japan.
[Kurihara, Toshihide] Keio Univ, Sch Med, Dept Ophthalmol, Shinjuku Ku, Tokyo 1608582, Japan.
[Kurihara, Toshihide] Keio Univ, Sch Med, Dept Orthoped Surg, Shinjuku Ku, Tokyo 1608582, Japan.
[Suda, Toshio] Keio Univ, Sch Med, Dept Cell Differentiat, Sakaguchi Lab,Shinjuku Ku, Tokyo 1608582, Japan.
[Mukouyama, Yoh-suke] NHLBI, Lab Stem Cell & Neurovasc Biol, Genet & Dev Biol Ctr, NIH, Bethesda, MD 20892 USA.
[Sato, Thomas N.] Japan Sci & Technol Agcy, ERATO Sato Live Bioforecasting Project, Kyoto 6190288, Japan.
[Sato, Thomas N.] Adv Telecommun Res Inst Int, Kyoto 6190288, Japan.
[Sato, Thomas N.] Dept Biomed Engn, Ithaca, NY 14850 USA.
[Sato, Thomas N.] Nara Inst Sci & Technol, Grad Sch Biol Sci, Nara 6300192, Japan.
[Sato, Thomas N.] Centenary Inst, Sydney, NSW 2050, Australia.
[Ema, Masatsugu] Shiga Univ Med Sci, Res Ctr Anim Life Sci, Otsu, Shiga 5202192, Japan.
RP Kubota, Y (reprint author), Keio Univ, Sch Med, Lab Vasc Biol, Shinjuku Ku, 35 Shinanomachi, Tokyo 1608582, Japan.
EM ykubo33@a3.keio.jp
RI Suda, Toshio/H-6761-2013;
OI Suda, Toshio/0000-0001-7540-1771; Kurihara,
Toshihide/0000-0002-5457-2720; Ema, Masatsugu/0000-0003-0645-6183
FU Ministry of Education, Culture, Sports, Science and Technology of Japan;
Takeda Science Foundation; Kanae Foundation; Mochida Memorial
Foundation; SENSHIN Medical Research Foundation; Daiichi Sankyo
Foundation of Life Science; Naito Foundation
FX We thank Toshihiro Nagai and Naoko Numata (Keio University) for their
technical supports, and Institute of Immunology (Utsunomiya, Japan) for
helping us generate some of the mutant mice. This work was supported by
Grants-in-Aid for Specially Promoted Research from the Ministry of
Education, Culture, Sports, Science and Technology of Japan, by a
research grant from Takeda Science Foundation, The Kanae Foundation, The
Mochida Memorial Foundation, SENSHIN Medical Research Foundation,
Daiichi Sankyo Foundation of Life Science, and The Naito Foundation.
NR 50
TC 33
Z9 33
U1 4
U2 16
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0092-8674
EI 1097-4172
J9 CELL
JI Cell
PD OCT 23
PY 2014
VL 159
IS 3
BP 584
EP 596
DI 10.1016/j.cell.2014.09.025
PG 13
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA AS8TU
UT WOS:000344521700014
PM 25417109
ER
PT J
AU Hussain, T
Llacer, JL
Fernandez, IS
Munoz, A
Martin-Marcos, P
Savva, CG
Lorsch, JR
Hinnebusch, AG
Ramakrishnan, V
AF Hussain, Tanweer
Llacer, Jose L.
Fernandez, Israel S.
Munoz, Antonio
Martin-Marcos, Pilar
Savva, Christos G.
Lorsch, Jon R.
Hinnebusch, Alan G.
Ramakrishnan, V.
TI Structural Changes Enable Start Codon Recognition by the Eukaryotic
Translation Initiation Complex
SO CELL
LA English
DT Article
ID 40S RIBOSOMAL-SUBUNIT; SELECTION IN-VIVO; EM STRUCTURE DETERMINATION;
C-TERMINAL DOMAIN; PREINITIATION COMPLEX; TRANSFER-RNA; AUG SELECTION;
CRYSTAL-STRUCTURE; FUNCTIONAL INTERACTIONS; ELECTRON-MICROSCOPY
AB During eukaryotic translation initiation, initiator tRNA does not insert fully into the P decoding site on the 40S ribosomal subunit. This conformation (POUT) is compatible with scanning mRNA for the AUG start codon. Base pairing with AUG is thought to promote isomerization to a more stable conformation (PIN) that arrests scanning and promotes dissociation of eIF1 from the 40S subunit. Here, we present a cryoEM reconstruction of a yeast preinitiation complex at 4.0 angstrom resolution with initiator tRNA in the PIN state, prior to eIF1 release. The structure reveals stabilization of the codon-anticodon duplex by the N-terminal tail of eIF1A, changes in the structure of eIF1 likely instrumental in its subsequent release, and changes in the conformation of eIF2. The mRNA traverses the entire mRNA cleft and makes connections to the regulatory domain of eIF2 alpha, eIF1A, and ribosomal elements that allow recognition of context nucleotides surrounding the AUG codon.
C1 [Hussain, Tanweer; Llacer, Jose L.; Fernandez, Israel S.; Savva, Christos G.; Ramakrishnan, V.] MRC, Mol Biol Lab, Cambridge CB2 0QH, England.
[Munoz, Antonio; Lorsch, Jon R.] Johns Hopkins Univ, Sch Med, Dept Biophys & Biophys Chem, Baltimore, MD 21205 USA.
[Martin-Marcos, Pilar; Hinnebusch, Alan G.] Eunice K Shriver Natl Inst Child Hlth & Human Dev, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA.
[Munoz, Antonio; Lorsch, Jon R.] Eunice K Shriver Natl Inst Child Hlth & Human Dev, Lab Mech & Regulat Prot Synth, NIH, Bethesda, MD 20892 USA.
RP Ramakrishnan, V (reprint author), MRC, Mol Biol Lab, Cambridge CB2 0QH, England.
EM ramak@mrc-lmb.cam.ac.uk
OI Lorsch, Jon/0000-0002-4521-4999; Ramakrishnan, V/0000-0002-4699-2194
FU UK Medical Research Council [MC_U105184332]; Wellcome Trust Senior
Investigator award [WT096570]; Agouron Institute; Jeantet Foundation;
NIH [GM62128]; Human Frontiers in Science Program [RGP-0028/2009];
Intramural Research Program of the NIH; EMBO; FEBS
FX We are grateful to Shaoxia Chen and Greg McMullan for technical support
with cryo-EM, Toby Darling and Jake Grimmett for help with computing,
Xiao-Chen Bai and Sjors H.W. Scheres for help and advice with EM data
processing, and Garib Murshudov and Alan Brown for help with refinement
of the atomic coordinates. We also thank Fan Zhang for providing the
purified Sui3-2 mutant of eIF2, Jinsheng Dong for sharing his genetic
findings on the U31:A39 tRNAi variant prior to publication,
Ann Kelley and Sarah Walker for providing reagents and advice, and
Thomas Dever for his insightful suggestion to employ Sui-
variants. T.H. and J.L.L. were, respectively, supported by postdoctoral
fellowships from EMBO and FEBS. This work was funded by grants to V.R.
from the UK Medical Research Council (MC_U105184332), Wellcome Trust
Senior Investigator award (WT096570), the Agouron Institute and the
Jeantet Foundation, from the NIH (GM62128) previously to J.R.L., and
from the Human Frontiers in Science Program (RGP-0028/2009) to A.G.H.,
J.R.L., and V.R., and by the Intramural Research Program of the NIH
(A.G.H., P.M.-M., J.R.L., and A.M.).
NR 54
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Z9 42
U1 0
U2 24
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0092-8674
EI 1097-4172
J9 CELL
JI Cell
PD OCT 23
PY 2014
VL 159
IS 3
BP 597
EP 607
DI 10.1016/j.cell.2014.10.001
PG 11
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA AS8TU
UT WOS:000344521700015
PM 25417110
ER
PT J
AU Agrawal, N
Akbani, R
Aksoy, BA
Ally, A
Arachchi, H
Asa, SL
Auman, JT
Balasundaram, M
Balu, S
Baylin, SB
Behera, M
Bernard, B
Beroukhim, R
Bishop, JA
Black, AD
Bodenheimer, T
Boice, L
Bootwalla, MS
Bowen, J
Bowlby, R
Bristow, CA
Brookens, R
Brooks, D
Bryant, R
Buda, E
Butterfield, YSN
Carling, T
Carlsen, R
Carter, SL
Carty, SE
Chan, TA
Chen, AY
Cherniack, AD
Cheung, D
Chin, L
Cho, J
Chu, A
Chuah, E
Cibulskis, K
Ciriello, G
Clarke, A
Clayman, GL
Cope, L
Copland, JA
Covington, K
Danilova, L
Davidsen, T
Demchok, JA
DiCara, D
Dhalla, N
Dhir, R
Dookran, SS
Dresdner, G
Eldridge, J
Eley, G
El-Naggar, AK
Eng, S
Fagin, JA
Fennell, T
Ferris, RL
Fisher, S
Frazer, S
Frick, J
Gabriel, SB
Ganly, I
Gao, JJ
Garraway, LA
Gastier-Foster, JM
Getz, G
Gehlenborg, N
Ghossein, R
Gibbs, RA
Giordano, TJ
Gomez-Hernandez, K
Grimsby, J
Gross, B
Guin, R
Hadjipanayis, A
Harper, HA
Hayes, DN
Heiman, DI
Herman, JG
Hoadley, KA
Hofree, M
Holt, RA
Hoyle, AP
Huang, FW
Huang, M
Hutter, CM
Ideker, T
Iype, L
Jacobsen, A
Jefferys, SR
Jones, CD
Jones, SJM
Kasaian, K
Kebebew, E
Khuri, FR
Kim, J
Kramer, R
Kreisberg, R
Kucherlapati, R
Kwiatkowski, DJ
Ladanyi, M
Lai, PH
Laird, PW
Lander, E
Lawrence, MS
Lee, D
Lee, E
Lee, S
Lee, W
Leraas, KM
Lichtenberg, TM
Lichtenstein, L
Lin, P
Ling, SY
Liu, JZ
Liu, WB
Liu, YC
LiVolsi, VA
Lu, YL
Ma, Y
Mahadeshwar, HS
Marra, MA
Mayo, M
McFadden, DG
Meng, SW
Meyerson, M
Mieczkowski, PA
Miller, M
Mills, G
Moore, RA
Mose, LE
Mungall, AJ
Murray, BA
Nikiforov, YE
Noble, MS
Ojesina, AI
Owonikoko, TK
Ozenberger, BA
Pantazi, A
Parfenov, M
Park, PJ
Parker, JS
Paull, EO
Pedamallu, CS
Perou, CM
Prins, JF
Protopopov, A
Ramalingam, SS
Ramirez, NC
Ramirez, R
Raphael, BJ
Rathmell, WK
Ren, XJ
Reynolds, SM
Rheinbay, E
Ringel, MD
Rivera, M
Roach, J
Robertson, AG
Rosenberg, MW
Rosenthal, M
Sadeghi, S
Saksena, G
Sander, C
Santoso, N
Schein, JE
Schultz, N
Schumacher, SE
Seethala, RR
Seidman, J
Senbabaoglu, Y
Seth, S
Sharpe, S
Shaw, KRM
Shen, JP
Shen, RL
Sherman, S
Sheth, M
Shi, Y
Shmulevich, I
Sica, GL
Simons, JV
Sinha, R
Sipahimalani, P
Smallridge, RC
Sofia, HJ
Soloway, MG
Song, XZ
Sougnez, C
Stewart, C
Stojanov, P
Stuart, JM
Sumer, SO
Sun, YC
Tabak, B
Tam, A
Tan, DH
Tang, JB
Tarnuzzer, R
Taylor, BS
Thiessen, N
Thorne, L
Thorsson, V
Tuttle, RM
Umbricht, CB
Van Den Berg, DJ
Vandin, F
Veluvolu, U
Verhaak, RGW
Vinco, M
Voet, D
Walter, V
Wang, ZN
Waring, S
Weinberger, PM
Weinhold, N
Weinstein, JN
Weisenberger, DJ
Wheeler, D
Wilkerson, MD
Wilson, J
Williams, M
Winer, DA
Wise, L
Wu, JY
Xi, L
Xu, AW
Yang, LM
Yang, LX
Zack, TI
Zeiger, MA
Zeng, D
Zenklusen, JC
Zhao, N
Zhang, HL
Zhang, JH
Zhang, JS
Zhang, W
Zmuda, E
Zou, LH
AF Agrawal, Nishant
Akbani, Rehan
Aksoy, B. Arman
Ally, Adrian
Arachchi, Harindra
Asa, Sylvia L.
Auman, J. Todd
Balasundaram, Miruna
Balu, Saianand
Baylin, Stephen B.
Behera, Madhusmita
Bernard, Brady
Beroukhim, Rameen
Bishop, Justin A.
Black, Aaron D.
Bodenheimer, Tom
Boice, Lori
Bootwalla, Moiz S.
Bowen, Jay
Bowlby, Reanne
Bristow, Christopher A.
Brookens, Robin
Brooks, Denise
Bryant, Robert
Buda, Elizabeth
Butterfield, Yaron S. N.
Carling, Tobias
Carlsen, Rebecca
Carter, Scott L.
Carty, Sally E.
Chan, Timothy A.
Chen, Amy Y.
Cherniack, Andrew D.
Cheung, Dorothy
Chin, Lynda
Cho, Juok
Chu, Andy
Chuah, Eric
Cibulskis, Kristian
Ciriello, Giovanni
Clarke, Amanda
Clayman, Gary L.
Cope, Leslie
Copland, John A.
Covington, Kyle
Danilova, Ludmila
Davidsen, Tanja
Demchok, John A.
DiCara, Daniel
Dhalla, Noreen
Dhir, Rajiv
Dookran, Sheliann S.
Dresdner, Gideon
Eldridge, Jonathan
Eley, Greg
El-Naggar, Adel K.
Eng, Stephanie
Fagin, James A.
Fennell, Timothy
Ferris, Robert L.
Fisher, Sheila
Frazer, Scott
Frick, Jessica
Gabriel, Stacey B.
Ganly, Ian
Gao, Jianjiong
Garraway, Levi A.
Gastier-Foster, Julie M.
Getz, Gad
Gehlenborg, Nils
Ghossein, Ronald
Gibbs, Richard A.
Giordano, Thomas J.
Gomez-Hernandez, Karen
Grimsby, Jonna
Gross, Benjamin
Guin, Ranabir
Hadjipanayis, Angela
Harper, Hollie A.
Hayes, D. Neil
Heiman, David I.
Herman, James G.
Hoadley, Katherine A.
Hofree, Matan
Holt, Robert A.
Hoyle, Alan P.
Huang, Franklin W.
Huang, Mei
Hutter, Carolyn M.
Ideker, Trey
Iype, Lisa
Jacobsen, Anders
Jefferys, Stuart R.
Jones, Corbin D.
Jones, Steven J. M.
Kasaian, Katayoon
Kebebew, Electron
Khuri, Fadlo R.
Kim, Jaegil
Kramer, Roger
Kreisberg, Richard
Kucherlapati, Raju
Kwiatkowski, David J.
Ladanyi, Marc
Lai, Phillip H.
Laird, Peter W.
Lander, Eric
Lawrence, Michael S.
Lee, Darlene
Lee, Eunjung
Lee, Semin
Lee, William
Leraas, Kristen M.
Lichtenberg, Tara M.
Lichtenstein, Lee
Lin, Pei
Ling, Shiyun
Liu, Jinze
Liu, Wenbin
Liu, Yingchun
LiVolsi, Virginia A.
Lu, Yiling
Ma, Yussanne
Mahadeshwar, Harshad S.
Marra, Marco A.
Mayo, Michael
McFadden, David G.
Meng, Shaowu
Meyerson, Matthew
Mieczkowski, Piotr A.
Miller, Michael
Mills, Gordon
Moore, Richard A.
Mose, Lisle E.
Mungall, Andrew J.
Murray, Bradley A.
Nikiforov, Yuri E.
Noble, Michael S.
Ojesina, Akinyemi I.
Owonikoko, Taofeek K.
Ozenberger, Bradley A.
Pantazi, Angeliki
Parfenov, Michael
Park, Peter J.
Parker, Joel S.
Paull, Evan O.
Pedamallu, Chandra Sekhar
Perou, Charles M.
Prins, Jan F.
Protopopov, Alexei
Ramalingam, Suresh S.
Ramirez, Nilsa C.
Ramirez, Ricardo
Raphael, Benjamin J.
Rathmell, W. Kimryn
Ren, Xiaojia
Reynolds, Sheila M.
Rheinbay, Esther
Ringel, Matthew D.
Rivera, Michael
Roach, Jeffrey
Robertson, A. Gordon
Rosenberg, Mara W.
Rosenthal, Matthew
Sadeghi, Sara
Saksena, Gordon
Sander, Chris
Santoso, Netty
Schein, Jacqueline E.
Schultz, Nikolaus
Schumacher, Steven E.
Seethala, Raja R.
Seidman, Jonathan
Senbabaoglu, Yasin
Seth, Sahil
Sharpe, Samantha
Shaw, Kenna R. Mills
Shen, John P.
Shen, Ronglai
Sherman, Steven
Sheth, Margi
Shi, Yan
Shmulevich, Ilya
Sica, Gabriel L.
Simons, Janae V.
Sinha, Rileen
Sipahimalani, Payal
Smallridge, Robert C.
Sofia, Heidi J.
Soloway, Matthew G.
Song, Xingzhi
Sougnez, Carrie
Stewart, Chip
Stojanov, Petar
Stuart, Joshua M.
Sumer, S. Onur
Sun, Yichao
Tabak, Barbara
Tam, Angela
Tan, Donghui
Tang, Jiabin
Tarnuzzer, Roy
Taylor, Barry S.
Thiessen, Nina
Thorne, Leigh
Thorsson, Vesteinn
Tuttle, R. Michael
Umbricht, Christopher B.
Van Den Berg, David J.
Vandin, Fabio
Veluvolu, Umadevi
Verhaak, Roel G. W.
Vinco, Michelle
Voet, Doug
Walter, Vonn
Wang, Zhining
Waring, Scot
Weinberger, Paul M.
Weinhold, Nils
Weinstein, John N.
Weisenberger, Daniel J.
Wheeler, David
Wilkerson, Matthew D.
Wilson, Jocelyn
Williams, Michelle
Winer, Daniel A.
Wise, Lisa
Wu, Junyuan
Xi, Liu
Xu, Andrew W.
Yang, Liming
Yang, Lixing
Zack, Travis I.
Zeiger, Martha A.
Zeng, Dong
Zenklusen, Jean Claude
Zhao, Ni
Zhang, Hailei
Zhang, Jianhua
Zhang, Jiashan (Julia)
Zhang, Wei
Zmuda, Erik
Zou, Lihua
CA Canc Genome Atlas Res Network
TI Integrated Genomic Characterization of Papillary Thyroid Carcinoma
SO CELL
LA English
DT Article
ID ACTIVATED RAS ONCOGENES; TERT PROMOTER MUTATIONS; BRAF MUTATIONS; HUMAN
CANCERS; PATHWAY; FUSION; GENES; CELLS; BRAF(V600E); NODULES
AB Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer. Here, we describe the genomic landscape of 496 PTCs. We observed a low frequency of somatic alterations (relative to other carcinomas) and extended the set of known PTC driver alterations to include EIF1AX, PPM1D, and CHEK2 and diverse gene fusions. These discoveries reduced the fraction of PTC cases with unknown oncogenic driver from 25% to 3.5%. Combined analyses of genomic variants, gene expression, and methylation demonstrated that different driver groups lead to different pathologies with distinct signaling and differentiation characteristics. Similarly, we identified distinct molecular subgroups of BRAF-mutant tumors, and multidimensional analyses highlighted a potential involvement of onco-miRs in less-differentiated subgroups. Our results propose a reclassification of thyroid cancers into molecular subtypes that better reflect their underlying signaling and differentiation properties, which has the potential to improve their pathological classification and better inform the management of the disease.
C1 [Giordano, Thomas J.; Canc Genome Atlas Res Network] NCI, Canc Genome Atlas Program Off, NIH, Bethesda, MD 20892 USA.
RP Giordano, TJ (reprint author), NCI, Canc Genome Atlas Program Off, NIH, 31 Ctr Dr,Bldg 31,Suite 3A20, Bethesda, MD 20892 USA.
EM gadgetz@broadinstitute.org; giordano@umich.edu
RI Zhao, Ni/P-9086-2014; Laird, Peter/G-8683-2012; Jacobsen,
Anders/K-1081-2013; Ling, Shiyun/P-2242-2014; Schein,
Jacquie/G-3674-2015; Weinberger, Paul/B-7007-2008; Holt,
Robert/C-3303-2009; Jones, Steven/C-3621-2009; Lee, Semin/S-2629-2016;
Marra, Marco/B-5987-2008;
OI Sinha, Rileen/0000-0001-5497-5055; Perou, Charles/0000-0001-9827-2247;
Gehlenborg, Nils/0000-0003-0327-8297; Sherman,
Steven/0000-0002-3079-5153; Zhao, Ni/0000-0002-7762-3949; Jacobsen,
Anders/0000-0001-6847-4980; Weinberger, Paul/0000-0002-5885-2631; Lee,
Semin/0000-0002-9015-6046; Seth, Sahil/0000-0003-4579-3959
FU United States National Institutes of Health [5U24CA143799, 5U24CA143835,
5U24CA143840, 5U24CA143843, 5U24CA143845, 5U24CA143848, 5U24CA143858,
5U24CA143866, 5U24CA143867, 5U24CA143882, 5U24CA143883, 5U24CA144025,
U54HG003067, U54HG003079, U54HG003273, P30CA16672]
FX We are grateful to all the patients and families who contributed to this
study, to Chris Gunter for editing, and Margi Sheth and Jiashan (Julia)
Zhang for project management. Thomas Giordano thanks his colleagues who
covered his clinical duties. Supported by the following grants from the
United States National Institutes of Health: 5U24CA143799, 5U24CA143835,
5U24CA143840, 5U24CA143843, 5U24CA143845, 5U24CA143848, 5U24CA143858,
5U24CA143866, 5U24CA143867, 5U24CA143882, 5U24CA143883, 5U24CA144025,
U54HG003067, U54HG003079, and U54HG003273, P30CA16672. Yuri Nikiforov is
a consultant for Quest Diagnostics. Raju Kucherlapati serves on the
Board of Directors of KEW Group, Inc. Daniel J. Weisenberger is a
consultant for Zymo Research Corporation.
NR 69
TC 146
Z9 149
U1 8
U2 47
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0092-8674
EI 1097-4172
J9 CELL
JI Cell
PD OCT 23
PY 2014
VL 159
IS 3
BP 676
EP 690
DI 10.1016/j.cell.2014.09.050
PG 15
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA AS8TU
UT WOS:000344521700021
ER
PT J
AU Porat-Shliom, N
Chen, Y
Tora, M
Shitara, A
Masedunskas, A
Weigert, R
AF Porat-Shliom, Natalie
Chen, Yun
Tora, Muhibullah
Shitara, Akiko
Masedunskas, Andrius
Weigert, Roberto
TI In Vivo Tissue-wide Synchronization of Mitochondrial Metabolic
Oscillations
SO CELL REPORTS
LA English
DT Article
ID SALIVARY ACINAR-CELLS; PANCREATIC-ISLETS; CARDIAC MYOCYTES; OXIDATIVE
STRESS; CA2+; MODULATION; MICROSCOPY; CARDIOMYOCYTES; FLUORESCENCE;
STIMULATION
AB Little is known about the spatiotemporal coordination of mitochondrial metabolism in multicellular organisms in situ. Using intravital microscopy in live animals, we report that mitochondrial metabolism undergoes rapid and periodic oscillations under basal conditions. Notably, mitochondria in vivo behave as a network of functionally coupled oscillators, which maintain a high level of coordination throughout the tissue via the activity of gap junctions. These findings reveal a unique aspect of the relationship between tissue architecture and self-organization of mitochondrial metabolism in vivo.
C1 [Porat-Shliom, Natalie; Tora, Muhibullah; Shitara, Akiko; Masedunskas, Andrius; Weigert, Roberto] Natl Inst Dent & Craniofacial Res, Intracellular Membrane Trafficking Unit, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA.
[Chen, Yun] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA.
RP Weigert, R (reprint author), Natl Inst Dent & Craniofacial Res, Intracellular Membrane Trafficking Unit, Oral & Pharyngeal Canc Branch, NIH, 30 Convent Dr 303A, Bethesda, MD 20892 USA.
EM weigertr@mail.nih.gov
OI Chen, Yun/0000-0001-6917-7814
FU NIH, National Institute of Dental and Craniofacial Research
FX This research was supported by the Intramural Research Program of the
NIH, National Institute of Dental and Craniofacial Research. We would
like to thank Drs. Donaldson, Finkel, Gutkind, Muallem, and Randazzo for
critical reading of the manuscript.
NR 43
TC 7
Z9 7
U1 2
U2 8
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 OCT 23
PY 2014
VL 9
IS 2
BP 514
EP 521
DI 10.1016/j.celrep.2014.09.022
PG 8
WC Cell Biology
SC Cell Biology
GA AS7YZ
UT WOS:000344469100012
PM 25373899
ER
PT J
AU Piguel, NH
Fievre, S
Blanc, JM
Carta, M
Moreau, MM
Moutin, E
Pinheiro, VL
Medina, C
Ezan, J
Lasvaux, L
Loll, F
Durand, CM
Chang, K
Petralia, RS
Wenthold, RJ
Stephenson, FA
Vuillard, L
Darbon, H
Perroy, J
Mulle, C
Montcouquiol, M
Racca, C
Sans, N
AF Piguel, Nicolas H.
Fievre, Sabine
Blanc, Jean-Michel
Carta, Mario
Moreau, Maite M.
Moutin, Enora
Pinheiro, Vera L.
Medina, Chantal
Ezan, Jerome
Lasvaux, Lea
Loll, Francois
Durand, Christelle M.
Chang, Kai
Petralia, Ronald S.
Wenthold, Robert J.
Stephenson, F. Anne
Vuillard, Laurent
Darbon, Herve
Perroy, Julie
Mulle, Christophe
Montcouquiol, Mireille
Racca, Claudia
Sans, Nathalie
TI Scribble1/AP2 Complex Coordinates NMDA Receptor Endocytic Recycling
SO CELL REPORTS
LA English
DT Article
ID CASEIN KINASE 2; EXCITATORY SYNAPSES; SYNAPTIC PLASTICITY; EXOCYST
COMPLEX; PDZ PROTEINS; NR2B SUBUNIT; TRAFFICKING; PHOSPHORYLATION;
INTERNALIZATION; PSD-95
AB The appropriate trafficking of glutamate receptors to synapses is crucial for basic synaptic function and synaptic plasticity. It is now accepted that NMDA receptors (NMDARs) internalize and are recycled at the plasma membrane but also exchange between synaptic and extrasynaptic pools; these NMDAR properties are also key to governing synaptic plasticity. Scribble1 is a large PDZ protein required for synaptogenesis and synaptic plasticity. Herein, we show that the level of Scribble1 is regulated in an activity-dependent manner and that Scribble1 controls the number of NMDARs at the plasma membrane. Notably, Scribble1 prevents GluN2A subunits from undergoing lysosomal trafficking and degradation by increasing their recycling to the plasma membrane following NMDAR activation. Finally, we show that a specific YxxR motif on Scribble1 controls these mechanisms through a direct interaction with AP2. Altogether, our findings define a molecular mechanism to control the levels of synaptic NMDARs via Scribble1 complex signaling.
C1 [Piguel, Nicolas H.; Blanc, Jean-Michel; Moreau, Maite M.; Pinheiro, Vera L.; Medina, Chantal; Ezan, Jerome; Lasvaux, Lea; Loll, Francois; Durand, Christelle M.; Montcouquiol, Mireille; Sans, Nathalie] Neuroctr Magendie, INSERM, U862, F-33000 Bordeaux, France.
[Piguel, Nicolas H.; Moreau, Maite M.; Pinheiro, Vera L.; Medina, Chantal; Ezan, Jerome; Lasvaux, Lea; Loll, Francois; Durand, Christelle M.; Montcouquiol, Mireille; Sans, Nathalie] Univ Bordeaux, Neuroctr Magendie, U862, F-33000 Bordeaux, France.
[Fievre, Sabine; Carta, Mario; Mulle, Christophe] Univ Bordeaux, Inst Interdisciplinaire Neurosci, UMR 5297, F-33000 Bordeaux, France.
[Fievre, Sabine; Carta, Mario; Mulle, Christophe] CNRS, Inst Interdisciplinaire Neurosci, UMR 5297, F-33000 Bordeaux, France.
[Blanc, Jean-Michel; Darbon, Herve] Aix Marseille Univ, CNRS, UMR7257, F-13288 Marseille, France.
[Blanc, Jean-Michel; Vuillard, Laurent] BioXtal Struct Biol Unit, F-13288 Marseille, France.
[Perroy, Julie] CNRS, UMR 5203, Inst Genom Fonctionnelle, F-34000 Montpellier, France.
[Moutin, Enora; Perroy, Julie] INSERM, U661, F-34000 Montpellier, France.
[Moutin, Enora; Perroy, Julie] Univ Montpellier I, F-34000 Montpellier, France.
[Moutin, Enora; Perroy, Julie] Univ Montpellier 2, UMR 5203, F-34000 Montpellier, France.
[Petralia, Ronald S.; Wenthold, Robert J.] NIDCD, Neurochem Lab, NIH, Bethesda, MD 20892 USA.
[Petralia, Ronald S.] NIDCD, Adv Imaging Core, NIH, Bethesda, MD 20892 USA.
[Stephenson, F. Anne] UCL, Sch Pharm, London WC1N 1AX, England.
[Racca, Claudia] Newcastle Univ, Inst Neurosci, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England.
RP Sans, N (reprint author), Neuroctr Magendie, INSERM, U862, F-33000 Bordeaux, France.
EM nathalie.sans@inserm.fr
OI Piguel, Nicolas/0000-0002-3193-2869; Carta, Mario/0000-0003-1225-2742;
Mulle, Christophe/0000-0003-2709-6615; montcouquiol,
mireille/0000-0001-8739-6519
FU Labex BRAIN [ANR-10-LABX-43]; Sequencing facility (Bordeaux University);
Electron Microscopy Research Services (Faculty of Medical Sciences,
Newcastle University); INSERM; INSERM AVENIR grants; Conseil Regional
d'Aquitaine; Neurocampus program; La Fondation pour la Recherche
Medicale; ANR NeuroScrib [ANR-07-NEUR-031-01]; ANR MossyPCP
[ANR-12-BSV4-0016-01]; Conseil Regional d'Aquitaine/INSERM; FRM Bourse
de soudure fellowship; Cifre Program; European ITN SyMBaD; FRM 4eme
annee de these [FDT20130928124]; FRM [SPF20081215186]; BioXtal SARL;
Royal Society; Wellcome Trust; Faculty of Medical Sciences, Newcastle
University; NIDCD/NIH
FX We thank M.C. Donat, D. Arma, E. Richard, and Y.-X. Wang for technical
assistance. We thank I. Macara for the GFP-Scrib constructs, J.P. Borg
for the Lano and Erbin antibodies and the HA-Scrib1 construct, K. Roche
for supplying the Tac constructs, T. Galli for the CD63 cDNA, P.D. Stahl
for the Rab5 cDNAs, F. Luton for the EFA6 mutated construct, G. Kohr for
the GluN monoclonal antibodies, and M. Garret for supplying the beta 3
cDNA and antibody. We also thank the Biochemistry and Biophysics
Facility of the Bordeaux Neurocampus funded by the Labex BRAIN
(ANR-10-LABX-43), the Sequencing facility (Bordeaux University), and the
Electron Microscopy Research Services (Faculty of Medical Sciences,
Newcastle University). This work was supported by INSERM and INSERM
AVENIR grants to N.S. and M.M., Conseil Regional d'Aquitaine (to N.S.
and M.M.), Neurocampus program (to M.M.), La Fondation pour la Recherche
Medicale (to N.S. and M.M.), ANR NeuroScrib ANR-07-NEUR-031-01 (to N.S.
and M.M.), ANR MossyPCP ANR-12-BSV4-0016-01 (to N.S. and C. Mulle),
Conseil Regional d'Aquitaine/INSERM Ph.D. fellowship and FRM Bourse de
soudure fellowship (to N.P.), the Cifre Program (to J.-M.B.), the
European ITN SyMBaD and FRM 4eme annee de these FDT20130928124 (to
V.L.P.), FRM fellowships SPF20081215186 (to C.M.D.), BioXtal SARL (to
L.V.), Royal Society International Joint Project grant (to C.R. and
N.S.), and the Wellcome Trust Institutional Strategic Support Fund
Project, Faculty of Medical Sciences, Newcastle University (to C.R.).
K.C., R.S.P., and R.J.W. were supported by the Intramural Research
Program of NIDCD/NIH. The M.M. and N.S. and the C.M. labs are members of
the Labex BRAIN.
NR 46
TC 9
Z9 9
U1 1
U2 8
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 OCT 23
PY 2014
VL 9
IS 2
BP 712
EP 727
DI 10.1016/j.celrep.2014.09.017
PG 16
WC Cell Biology
SC Cell Biology
GA AS7YZ
UT WOS:000344469100028
PM 25310985
ER
PT J
AU Sung, MH
Guertin, MJ
Baek, S
Hager, GL
AF Sung, Myong-Hee
Guertin, Michael J.
Baek, Songjoon
Hager, Gordon L.
TI DNase Footprint Signatures Are Dictated by Factor Dynamics and DNA
Sequence
SO MOLECULAR CELL
LA English
DT Article
ID GLUCOCORTICOID-RECEPTOR BINDING; CHROMATIN ACCESSIBILITY; IN-VIVO;
TRANSCRIPTION; PROTEIN; GENOME; EXCHANGE; CELLS; ELEMENTS; SCALE
AB Genomic footprinting has emerged as an unbiased discovery method for transcription factor (TF) occupancy at cognate DNA in vivo. A basic premise of footprinting is that sequence-specific TF-DNA interactions are associated with localized resistance to nucleases, leaving observable signatures of cleavage within accessible chromatin. This phenomenon is interpreted to imply protection of the critical nucleotides by the stably bound protein factor. However, this model conflicts with previous reports of many TFs exchanging with specific binding sites in living cells on a timescale of seconds. We show that TFs with short DNA residence times have no footprints at bound motif elements. Moreover, the nuclease cleavage profile within a footprint originates from the DNA sequence in the factor-binding site, rather than from the protein occupying specific nucleotides. These findings suggest a revised understanding of TF footprinting and reveal limitations in comprehensive reconstruction of the TF regulatory network using this approach.
C1 [Sung, Myong-Hee; Guertin, Michael J.; Baek, Songjoon; Hager, Gordon L.] NCI, Lab Receptor Biol & Gene Express, NIH, Bethesda, MD 20892 USA.
RP Hager, GL (reprint author), NCI, Lab Receptor Biol & Gene Express, NIH, Bldg 41,41 Lib Dr, Bethesda, MD 20892 USA.
EM hagerg@exchange.nih.gov
FU NIH, National Cancer Institute, Center for Cancer Research
FX Extensive use was made of the NIH Biowulf cluster, a GNU/Linux parallel
processing system for computational analysis; we acknowledge the NIH
Helix Systems Staff for management of this system. This research was
supported by the Intramural Research Program of the NIH, National Cancer
Institute, Center for Cancer Research.
NR 48
TC 36
Z9 36
U1 1
U2 9
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1097-2765
EI 1097-4164
J9 MOL CELL
JI Mol. Cell
PD OCT 23
PY 2014
VL 56
IS 2
BP 275
EP 285
DI 10.1016/j.molcel.2014.08.016
PG 11
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA AS8FE
UT WOS:000344484600009
PM 25242143
ER
PT J
AU Pancera, M
Zhou, TQ
Druz, A
Georgiev, IS
Soto, C
Gorman, J
Huang, JH
Acharya, P
Chuang, GY
Ofek, G
Stewart-Jones, GBE
Stuckey, J
Bailer, RT
Joyce, MG
Louder, MK
Tumba, N
Yang, YP
Zhang, BS
Cohen, MS
Haynes, BF
Mascola, JR
Morris, L
Munro, JB
Blanchard, SC
Mothes, W
Connors, M
Kwong, PD
AF Pancera, Marie
Zhou, Tongqing
Druz, Aliaksandr
Georgiev, Ivelin S.
Soto, Cinque
Gorman, Jason
Huang, Jinghe
Acharya, Priyamvada
Chuang, Gwo-Yu
Ofek, Gilad
Stewart-Jones, Guillaume B. E.
Stuckey, Jonathan
Bailer, Robert T.
Joyce, M. Gordon
Louder, Mark K.
Tumba, Nancy
Yang, Yongping
Zhang, Baoshan
Cohen, Myron S.
Haynes, Barton F.
Mascola, John R.
Morris, Lynn
Munro, James B.
Blanchard, Scott C.
Mothes, Walther
Connors, Mark
Kwong, Peter D.
TI Structure and immune recognition of trimeric pre-fusion HIV-1 Env
SO NATURE
LA English
DT Article
ID IMMUNODEFICIENCY-VIRUS TYPE-1; RESPIRATORY SYNCYTIAL VIRUS; GP120
ENVELOPE GLYCOPROTEIN; NEUTRALIZING ANTIBODY PG9; INFLUENZA-A VIRUSES;
B-CELL RESPONSES; MEMBRANE-FUSION; CRYSTAL-STRUCTURE; RECEPTOR-BINDING;
EBOLA-VIRUS
AB The human immunodeficiency virus type 1 (HIV-1) envelope (Env) spike, comprising three gp120 and three gp41 subunits, is a conformational machine that facilitates HIV-1 entry by rearranging from a mature unliganded state, through receptor-bound intermediates, to a post-fusion state. As the sole viral antigen on the HIV-1 virion surface, Env is both the target of neutralizing antibodies and a focus of vaccine efforts. Here we report the structure at 3.5 angstrom resolution for an HIV-1 Env trimer captured in a mature closed state by antibodies PGT122 and 35O22. This structure reveals the pre-fusion conformation of gp41, indicates rearrangements needed for fusion activation, and defines parameters of immune evasion and immune recognition. Pre-fusion gp41 encircles amino- and carboxy-terminal strands of gp120 with four helices that form a membrane-proximal collar, fastened by insertion of a fusion peptide-proximal methionine into a gp41-tryptophan clasp. Spike rearrangements required for entry involve opening the clasp and expelling the termini. N-linked glycosylation and sequence-variable regions cover the pre-fusion closed spike; we used chronic cohorts to map the prevalence and location of effective HIV-1-neutralizing responses, which were distinguished by their recognition of N-linked glycan and tolerance for epitope-sequence variation.
C1 [Pancera, Marie; Zhou, Tongqing; Druz, Aliaksandr; Georgiev, Ivelin S.; Soto, Cinque; Gorman, Jason; Acharya, Priyamvada; Chuang, Gwo-Yu; Ofek, Gilad; Stewart-Jones, Guillaume B. E.; Stuckey, Jonathan; Bailer, Robert T.; Joyce, M. Gordon; Louder, Mark K.; Yang, Yongping; Zhang, Baoshan; Mascola, John R.; Kwong, Peter D.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Huang, Jinghe; Connors, Mark] NIAID, HIV Specif Immun Sect, Lab Immunoregulat, NIH, Bethesda, MD 20892 USA.
[Tumba, Nancy; Morris, Lynn] NHLS, Ctr HIV & STIs, Natl Inst Communicable Dis, ZA-2131 Johannesburg, South Africa.
[Cohen, Myron S.] Univ N Carolina, Dept Med, Chapel Hill, NC 27599 USA.
[Cohen, Myron S.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27599 USA.
[Cohen, Myron S.] Univ N Carolina, Dept Microbiol, Chapel Hill, NC 27599 USA.
[Cohen, Myron S.] Univ N Carolina, Dept Immunol, Chapel Hill, NC 27599 USA.
[Haynes, Barton F.] Duke Univ, Human Vaccine Inst, Sch Med, Dept Med, Durham, NC 27710 USA.
[Haynes, Barton F.] Duke Univ, Human Vaccine Inst, Sch Med, Dept Surg, Durham, NC 27710 USA.
[Haynes, Barton F.] Duke Univ, Human Vaccine Inst, Sch Med, Dept Pediat, Durham, NC 27710 USA.
[Haynes, Barton F.] Duke Univ, Human Vaccine Inst, Sch Med, Dept Immunol, Durham, NC 27710 USA.
[Haynes, Barton F.] Duke Univ, Ctr HIV AIDS Vaccine Immunol Immunogen Discovery, Durham, NC 27710 USA.
[Morris, Lynn] Univ Witwatersrand, ZA-2000 Johannesburg, South Africa.
[Morris, Lynn] Univ KwaZulu Natal, Ctr AIDS Programme Res South Africa CAPRISA, ZA-4041 Durban, South Africa.
[Munro, James B.; Mothes, Walther] Yale Univ, Dept Microbial Pathogenesis, New Haven, CT 06536 USA.
[Blanchard, Scott C.] Cornell Univ, Weill Cornell Med Coll, Dept Physiol & Biophys, New York, NY 10021 USA.
RP Kwong, PD (reprint author), NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM pdkwong@nih.gov
RI Zhou, Tongqing/A-6880-2010; Huang, Jinghe/O-1986-2015; Blanchard,
Scott/A-5804-2009
OI Zhou, Tongqing/0000-0002-3935-4637;
FU Vaccine Research Center, National Institute of Allergy and Infectious
Diseases (NIAID), National Institutes of Health (NIH); Division of AIDS,
NIAID, NIH [R21-AI100696, CHAVI-AI0678501, CHAVI-Immunogen
Discovery-AI100645]; National Institutes of General Medical Sciences
[P01-GM56550, R01-GM098859]; International AIDS Vaccine Initiative's
(IAVI's) Neutralizing Antibody Consortium; Bill & Melinda Gates
Foundation; Ministry of Foreign Affairs of Denmark; Irish Aid; Ministry
of Finance of Japan; Ministry of Foreign Affairs of the Netherlands;
Norwegian Agency for Development Cooperation (NORAD); UK Department for
International Development (DFID); United States Agency for International
Development (USAID); US Department of Energy, Basic Energy Sciences,
Office of Science [W-31-109-Eng-38]
FX We thank J. Binley for the JR-FL plasmid used in smFRET; D. Burton and
W. Koff for PGT122; J. Chrzas and SER-CAT staff for assistance with data
collection; B. Graham for discussions on RSV; R. Sanders for furin
plasmid; R. Schwartz and the Vaccine Production Program for antibody
VRC01; J. Sodroski for information on C34-Ig; I. Wilson for discussions
on pre-fusion Env structure; Z. Yang for assistance with cloning; G.
Nabel, G. Scott and members of the Structural Biology Section and
Structural Bioinformatics Core, Vaccine Research Center, for discussions
and comments on the manuscript; and the WCMC/AMC/TSRI HIVRAD team for
their contributions to the design and validation of near-native mimicry
for soluble BG505 SOSIP.664 trimers. 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. The authors
acknowledge the contributions of the Center for HIV/AIDS Vaccine
Discovery (CHAVI) Clinical Core Team for recruiting study participants
and carrying out all aspects of the CHAVI001 and CHAVI008 protocols at
Chapel Hill, North Carolina (J. Eron); Blantyre, Malawi (J. Kumwenda, T.
Taha); Lilongwe, Malawi (I. Hoffman, G. Kaminga); Johannesburg, South
Africa (H. Rees); Durban, South Africa (S. Abdool Karim); Moshi,
Tanzania (S. Noel, S. Kapiga, J. Crump); and London, UK (S. Fidler).
Support for this work was provided by the Intramural Research Program of
the Vaccine Research Center, National Institute of Allergy and
Infectious Diseases (NIAID), National Institutes of Health (NIH); and by
grants from the Division of AIDS, NIAID, NIH (R21-AI100696,
CHAVI-AI0678501, and CHAVI-Immunogen Discovery-AI100645), from the
National Institutes of General Medical Sciences (P01-GM56550 and
R01-GM098859), from the Irvington Fellows Program of the Cancer Research
Program, and from the International AIDS Vaccine Initiative's (IAVI's)
Neutralizing Antibody Consortium. IAVI's work is made possible by
support from many donors including: the Bill & Melinda Gates Foundation;
the Ministry of Foreign Affairs of Denmark; Irish Aid; the Ministry of
Finance of Japan; the Ministry of Foreign Affairs of the Netherlands;
the Norwegian Agency for Development Cooperation (NORAD); the UK
Department for International Development (DFID): and the United States
Agency for International Development (USAID). The full list of IAVI
donors is available at http://www.iavi.org. 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 127
TC 209
Z9 212
U1 18
U2 119
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 OCT 23
PY 2014
VL 514
IS 7523
BP 455
EP +
DI 10.1038/nature13808
PG 24
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AR7RC
UT WOS:000343775900032
PM 25296255
ER
PT J
AU Buskirk, AD
Green, BJ
Lemons, AR
Nayak, AP
Goldsmith, WT
Kashon, ML
Anderson, SE
Hettick, JM
Templeton, SP
Germolec, DR
Beezhold, DH
AF Buskirk, Amanda D.
Green, Brett J.
Lemons, Angela R.
Nayak, Ajay P.
Goldsmith, W. Travis
Kashon, Michael L.
Anderson, Stacey E.
Hettick, Justin M.
Templeton, Steven P.
Germolec, Dori R.
Beezhold, Donald H.
TI A Murine Inhalation Model to Characterize Pulmonary Exposure to Dry
Aspergillus fumigatus Conidia
SO PLOS ONE
LA English
DT Article
ID FUNGAL SPORES; C57BL/6 MICE; RESPONSES; ASTHMA; CELLS; MICROORGANISMS;
SENSITIZATION; GERMINATION; INFECTION; ALLERGENS
AB Most murine models of fungal exposure are based on the delivery of uncharacterized extracts or liquid conidia suspensions using aspiration or intranasal approaches. Studies that model exposure to dry fungal aerosols using whole body inhalation have only recently been described. In this study, we aimed to characterize pulmonary immune responses following repeated inhalation of conidia utilizing an acoustical generator to deliver dry fungal aerosols to mice housed in a nose only exposure chamber. Immunocompetent female BALB/cJ mice were exposed to conidia derived from Aspergillus fumigatus wild-type (WT) or a melanin-deficient (Delta alb1) strain. Conidia were aerosolized and delivered to mice at an estimated deposition dose of 1 x 10(5) twice a week for 4 weeks (8 total). Histopathological and immunological endpoints were assessed 4, 24, 48, and 72 hours after the final exposure. Histopathological analysis showed that conidia derived from both strains induced lung inflammation, especially at 24 and 48 hour time points. Immunological endpoints evaluated in bronchoalveolar lavage fluid (BALF) and the mediastinal lymph nodes showed that exposure to WT conidia led to elevated numbers of macrophages, granulocytes, and lymphocytes. Importantly, CD8(+) IL17(+) (Tc17) cells were significantly higher in BALF and positively correlated with germination of A. fumigatus WT spores. Germination was associated with specific IgG to intracellular proteins while Delta alb1 spores elicited antibodies to cell wall hydrophobin. These data suggest that inhalation exposures may provide a more representative analysis of immune responses following exposures to environmentally and occupationally prevalent fungal contaminants.
C1 [Buskirk, Amanda D.; Green, Brett J.; Lemons, Angela R.; Nayak, Ajay P.; Anderson, Stacey E.; Hettick, Justin M.; Templeton, Steven P.; Beezhold, Donald H.] NIOSH, Allergy & Clin Immunol Branch, Hlth Effects Lab Div, Ctr Dis Control & Prevent, Morgantown, WV 26505 USA.
[Goldsmith, W. Travis] NIOSH, Pathol & Physiol Res Branch, Hlth Effects Lab Div, Ctr Dis Control & Prevent, Morgantown, WV USA.
[Kashon, Michael L.] NIOSH, Biostat & Epidemiol Branch, Hlth Effects Lab Div, Ctr Dis Control & Prevent, Morgantown, WV USA.
[Germolec, Dori R.] Natl Inst Environm Hlth Sci, Natl Toxicol Program Div, Toxicol Branch, Res Triangle Pk, NC USA.
RP Beezhold, DH (reprint author), NIOSH, Allergy & Clin Immunol Branch, Hlth Effects Lab Div, Ctr Dis Control & Prevent, Morgantown, WV 26505 USA.
EM zec1@cdc.gov
OI Lemons, Angela/0000-0003-3057-9888
FU intramural National Institute for Occupational Safety and Health
(NIOSH); NIEHS IAA [AES 12007-00100000]
FX This study was supported by intramural National Institute for
Occupational Safety and Health (NIOSH) funding and by an interagency
agreement with NIEHS IAA# AES 12007-00100000. The funders had no role in
study design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 41
TC 4
Z9 4
U1 1
U2 10
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD OCT 23
PY 2014
VL 9
IS 10
AR e109855
DI 10.1371/journal.pone.0109855
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AR5ZY
UT WOS:000343662800019
PM 25340353
ER
PT J
AU Wright, GEB
Adeyemo, AA
Tiffin, N
AF Wright, Galen E. B.
Adeyemo, Adebowale A.
Tiffin, Nicki
TI Informed consent and ethical re-use of African genomic data
SO HUMAN GENOMICS
LA English
DT Letter
DE Informed consent; Secondary use; Ethics; Africa
ID CHALLENGES; COMMITTEES
AB Rapid advances in human genomic research are increasing the availability of genomic data for secondary analysis. Particularly in the case of vulnerable African populations, ethics and informed consent processes need to be transparent-both to ensure participant protection, as well as to share skills and to evolve best practice for informed consent from a shared knowledge base. An open dialogue between all stakeholders can facilitate this.
C1 [Wright, Galen E. B.; Tiffin, Nicki] Univ Western Cape, South Africa Bioinformat Unit, Med Res Council, South African Natl Bioinformat Inst, ZA-7535 Bellville, South Africa.
[Adeyemo, Adebowale A.] NHGRI, NIH, Bethesda, MD 20892 USA.
RP Tiffin, N (reprint author), Univ Western Cape, South Africa Bioinformat Unit, Med Res Council, South African Natl Bioinformat Inst, Private Bag X17, ZA-7535 Bellville, South Africa.
EM nicki@sanbi.ac.za
FU Intramural NIH HHS; Medical Research Council; NHGRI NIH HHS
[1U54HG006939, U41 HG006941, U41HG006941, U54 HG006939, Z01HG200362]
NR 14
TC 5
Z9 5
U1 0
U2 0
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1473-9542
EI 1479-7364
J9 HUM GENOMICS
JI Hum. Genomics
PD OCT 22
PY 2014
VL 8
AR 8
DI 10.1186/s40246-014-0018-7
PG 3
WC Genetics & Heredity
SC Genetics & Heredity
GA AW5GB
UT WOS:000346302800001
PM 25339190
ER
PT J
AU Lopez, AD
Williams, TN
Levin, A
Tonelli, M
Singh, JA
Burney, PGJ
Rehm, J
Volkow, ND
Koob, G
Ferri, CP
AF Lopez, Alan D.
Williams, Thomas N.
Levin, Adeera
Tonelli, Marcello
Singh, Jasvinder A.
Burney, Peter G. J.
Rehm, Juergen
Volkow, Nora D.
Koob, George
Ferri, Cleusa P.
TI Remembering the forgotten non-communicable diseases
SO BMC MEDICINE
LA English
DT Article
DE Global health; Non-communicable diseases; Sickle cell disease; Chronic
kidney disease; Asthma; Dementia; Gout; Substance abuse; Alcohol; Liver
cirrhosis
ID SICKLE-CELL-DISEASE; CHRONIC KIDNEY-DISEASE; LIVER-CIRRHOSIS MORTALITY;
GLOBAL BURDEN; SYSTEMATIC ANALYSIS; ALZHEIMERS-DISEASE; SERUM URATE;
UNITED-STATES; RISK-FACTOR; CARDIOVASCULAR-DISEASE
AB The forthcoming post-Millennium Development Goals era will bring about new challenges in global health. Low- and middle-income countries will have to contend with a dual burden of infectious and non-communicable diseases (NCDs). Some of these NCDs, such as neoplasms, COPD, cardiovascular diseases and diabetes, cause much health loss worldwide and are already widely recognised as doing so. However, 55% of the global NCD burden arises from other NCDs, which tend to be ignored in terms of premature mortality and quality of life reduction. Here, experts in some of these 'forgotten NCDs' review the clinical impact of these diseases along with the consequences of their ignoring their medical importance, and discuss ways in which they can be given higher global health priority in order to decrease the growing burden of disease and disability.
C1 [Lopez, Alan D.] Univ Melbourne, Sch Populat & Global Hlth, Melbourne, Vic 3053, Australia.
[Williams, Thomas N.] Univ London Imperial Coll Sci Technol & Med, St Marys Hosp, Dept Med, London W2 1NY, England.
[Williams, Thomas N.] KEMRI Wellcome Trust Res Programme, Kilifi, Kenya.
[Levin, Adeera] Univ British Columbia, St Pauls Hosp, Vancouver, BC V6Z 1Y8, Canada.
[Singh, Jasvinder A.] VA Med Ctr, Med Serv, Birmingham, AL USA.
[Singh, Jasvinder A.] VA Med Ctr, Ctr Surg Med Acute Care Res & Transit, Birmingham, AL USA.
[Singh, Jasvinder A.] Univ Alabama Birmingham, Sch Med, Dept Med, Birmingham, AL 35294 USA.
[Singh, Jasvinder A.] Univ Alabama Birmingham, Sch Publ Hlth, Div Epidemiol, Birmingham, AL 35294 USA.
[Singh, Jasvinder A.] Mayo Clin, Coll Med, Dept Orthoped Surg, Rochester, MN 55905 USA.
[Burney, Peter G. J.] Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, London, England.
[Rehm, Juergen] Ctr Addict & Mental Hlth, Toronto, ON, Canada.
[Rehm, Juergen] Tech Univ Dresden, D-01062 Dresden, Germany.
[Rehm, Juergen] Univ Toronto, Dalla Lana Sch Publ Hlth, Toronto, ON, Canada.
[Rehm, Juergen] Univ Toronto, Dept Psychiat, Toronto, ON, Canada.
[Rehm, Juergen] UofT, Inst Med Sci, Toronto, ON, Canada.
[Volkow, Nora D.] NIDA, NIH, Rockville, MD USA.
[Koob, George] NIAAA, NIH, Bethesda, MD 20892 USA.
[Ferri, Cleusa P.] Hosp Alemao Oswaldo Cruz, Inst Educ & Hlth Sci, BR-01323903 Sao Paulo, Brazil.
[Ferri, Cleusa P.] Univ Fed Sao Paulo, Escola Paulista Med, Dept Psychobiol, BR-04023062 Sao Paulo, Brazil.
RP Lopez, AD (reprint author), Univ Melbourne, Sch Populat & Global Hlth, Bldg 379,207 Bouverie St, Melbourne, Vic 3053, Australia.
EM alan.lopez@unimelb.edu.au
RI Ferri, Cleusa/B-2922-2010; Tonelli, Marcello/B-3028-2009; koob,
george/P-8791-2016
OI Ferri, Cleusa/0000-0002-1815-7685;
FU Merck
FX Cleusa Ferri has been named as a local principal investigator in an
upcoming trial sponsored by Merck.
NR 94
TC 8
Z9 8
U1 10
U2 22
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1741-7015
J9 BMC MED
JI BMC Med.
PD OCT 22
PY 2014
VL 12
AR 200
DI 10.1186/s12916-014-0200-8
PG 19
WC Medicine, General & Internal
SC General & Internal Medicine
GA AT4GU
UT WOS:000344898600001
PM 25604462
ER
PT J
AU Alavanja, MCR
Hofmann, JN
Lynch, CF
Hines, CJ
Barry, KH
Barker, J
Buckman, DW
Thomas, K
Sandler, DP
Hoppin, JA
Koutros, S
Andreotti, G
Lubin, JH
Blair, A
Freeman, LEB
AF Alavanja, Michael C. R.
Hofmann, Jonathan N.
Lynch, Charles F.
Hines, Cynthia J.
Barry, Kathryn H.
Barker, Joseph
Buckman, Dennis W.
Thomas, Kent
Sandler, Dale P.
Hoppin, Jane A.
Koutros, Stella
Andreotti, Gabriella
Lubin, Jay H.
Blair, Aaron
Freeman, Laura E. Beane
TI Non-Hodgkin Lymphoma Risk and Insecticide, Fungicide and Fumigant se in
the Agricultural Health Study
SO PLOS ONE
LA English
DT Article
ID PESTICIDE EXPOSURE; OCCUPATIONAL-EXPOSURE; CANCER-RISK; ADIPOSE-TISSUE;
UNITED-STATES; FARMERS; ORGANOCHLORINES; APPLICATORS; LINDANE; COHORT
AB Farming and pesticide use have previously been linked to non-Hodgkin lymphoma (NHL), chronic lymphocytic leukemia (CLL) and multiple myeloma (MM). We evaluated agricultural use of specific insecticides, fungicides, and fumigants and risk of NHL and NHL-subtypes (including CLL and MM) in a U.S.-based prospective cohort of farmers and commercial pesticide applicators. A total of 523 cases occurred among 54,306 pesticide applicators from enrollment (1993-97) through December 31, 2011 in Iowa, and December 31, 2010 in North Carolina. Information on pesticide use, other agricultural exposures and other factors was obtained from questionnaires at enrollment and at follow-up approximately five years later (1999-2005). Information from questionnaires, monitoring, and the literature were used to create lifetime-days and intensity-weighted lifetime days of pesticide use, taking into account exposure-modifying factors. Poisson and polytomous models were used to calculate relative risks (RR) and 95% confidence intervals (CI) to evaluate associations between 26 pesticides and NHL and five NHL-subtypes, while adjusting for potential confounding factors. For total NHL, statistically significant positive exposure-response trends were seen with lindane and DDT. Terbufos was associated with total NHL in ever/never comparisons only. In subtype analyses, terbufos and DDT were associated with small cell lymphoma/chronic lymphocytic leukemia/marginal cell lymphoma, lindane and diazinon with follicular lymphoma, and permethrin with MM. However, tests of homogeneity did not show significant differences in exposure-response among NHL-subtypes for any pesticide. Because 26 pesticides were evaluated for their association with NHL and its subtypes, some chance finding could have occurred. Our results showed pesticides from different chemical and functional classes were associated with an excess risk of NHL and NHL subtypes, but not all members of any single class of pesticides were associated with an elevated risk of NHL or NHL subtypes. These findings are among the first to suggest links between DDT, lindane, permethrin, diazinon and terbufos with NHL subtypes.
C1 [Alavanja, Michael C. R.; Hofmann, Jonathan N.; Barry, Kathryn H.; Koutros, Stella; Andreotti, Gabriella; Lubin, Jay H.; Blair, Aaron; Freeman, Laura E. Beane] NCI, Div Canc Epidemiol & Genet, Rockville, MD 20850 USA.
[Lynch, Charles F.] Univ Iowa, Coll Publ Hlth, Iowa City, IA USA.
[Hines, Cynthia J.] NIOSH, Cincinnati, OH 45226 USA.
[Barker, Joseph; Buckman, Dennis W.] IMS Inc, Calverton, MD USA.
[Thomas, Kent] US EPA, Natl Exposure Res Lab, Res Triangle Pk, NC 27711 USA.
[Sandler, Dale P.; Hoppin, Jane A.] NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA.
RP Alavanja, MCR (reprint author), NCI, Div Canc Epidemiol & Genet, Rockville, MD 20850 USA.
EM alavanjm@mail.nih.gov
RI Beane Freeman, Laura/C-4468-2015
OI Beane Freeman, Laura/0000-0003-1294-4124
FU Intramural Research Program of the NIH, National Cancer Institute,
Division of Cancer Epidemiology and Genetics [Z01CP010119]; National
Institutes of Environmental Health Sciences [Z01ES049030]; IMS, Inc
FX This work was supported by the Intramural Research Program of the NIH,
National Cancer Institute, Division of Cancer Epidemiology and Genetics
(Z01CP010119) and The National Institutes of Environmental Health
Sciences (Z01ES049030). The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript. IMS, Inc, provided support in the form of salaries for
authors Joseph Barker and Denis W Buckman, but did not have any
additional role in the study design, data collection and analysis,
decision to publish, or preparation of the manuscript. The specific
roles of these authors are articulated in the 'author contributions'
section.
NR 49
TC 12
Z9 12
U1 1
U2 13
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD OCT 22
PY 2014
VL 9
IS 10
AR e109332
DI 10.1371/journal.pone.0109332
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AR6DY
UT WOS:000343674800010
PM 25337994
ER
PT J
AU Kulkarni, V
Valentin, A
Rosati, M
Rolland, M
Mullins, JI
Pavlakis, GN
Felber, BK
AF Kulkarni, Viraj
Valentin, Antonio
Rosati, Margherita
Rolland, Morgane
Mullins, James I.
Pavlakis, George N.
Felber, Barbara K.
TI HIV-1 Conserved Elements p24CE DNA Vaccine Induces Humoral Immune
Responses with Broad Epitope Recognition in Macaques
SO PLOS ONE
LA English
DT Article
ID T-LYMPHOCYTE RESPONSES; RHESUS-MONKEYS; CELL RESPONSES; VIRAL LOAD;
ET-AL; REGIONS; BREADTH; ANTIBODIES; PROTEINS; COVERAGE
AB To target immune responses towards invariable regions of the virus, we engineered DNA-based immunogens encoding conserved elements (CE) of HIV-1 p24(gag). This conserved element vaccine is designed to avoid decoy epitopes by focusing responses to critical viral elements. We previously reported that vaccination of macaques with p24CE DNA induced robust cellular immune responses to CE that were not elicited upon wild type p55(gag) DNA vaccination. p24CE DNA priming followed by p55(gag) DNA boost provided a novel strategy to increase the magnitude and breadth of the cellular immune responses to HIV-1 Gag, including the induction of strong, multifunctional T-cell responses targeting epitopes within CE. Here, we examined the humoral responses induced upon p24CE DNA or p55(gag) DNA vaccination in macaques and found that although both vaccines induced robust p24(gag) binding antibody responses, the responses induced by p24CE DNA showed a unique broad range of linear epitope recognition. In contrast, antibodies elicited by p55(gag) DNA vaccine failed to recognize p24CE protein and did not recognize linear epitopes spanning the CE. Interestingly, boosting of p24CE DNA primed animals with p55(gag) DNA resulted in augmentation of antibodies able to recognize p24(gag) as well as the p24CE proteins, thereby inducing broadest immunity. Our results indicate that an effectively directed vaccine strategy that includes priming with the conserved element vaccine followed by boost with the complete immunogen induces broad cellular and humoral immunity focused on the conserved regions of the virus. This novel and effective strategy to broaden responses could be applied against other antigens of highly diverse pathogens.
C1 [Kulkarni, Viraj; Felber, Barbara K.] NCI, Human Retrovirus Pathogenesis Sect, Vaccine Branch, Ctr Canc Res, Frederick, MD 21701 USA.
[Valentin, Antonio; Rosati, Margherita; Pavlakis, George N.] NCI, Human Retrovirus Sect, Vaccine Branch, Ctr Canc Res, Frederick, MD 21701 USA.
[Rolland, Morgane; Mullins, James I.] Univ Washington, Dept Microbiol, Seattle, WA 98195 USA.
[Rolland, Morgane; Mullins, James I.] Univ Washington, Dept Med, Seattle, WA USA.
[Rolland, Morgane; Mullins, James I.] Univ Washington, Dept Lab Med, Seattle, WA 98195 USA.
RP Pavlakis, GN (reprint author), NCI, Human Retrovirus Sect, Vaccine Branch, Ctr Canc Res, Frederick, MD 21701 USA.
EM george.pavlakis@nih.gov; barbara.felber@nih.gov
FU Intramural Research Program of the National Cancer Institute, National
Institutes of Health (NCI/NIH); Public Health Services [AI57005]
FX This work was supported in part by the Intramural Research Program of
the National Cancer Institute, National Institutes of Health (NCI/NIH)
(BKF, GNP) and by Public Health Services grant AI57005 (to JIM). The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 36
TC 13
Z9 13
U1 0
U2 3
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD OCT 22
PY 2014
VL 9
IS 10
AR e111085
DI 10.1371/journal.pone.0111085
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AR6DY
UT WOS:000343674800103
PM 25338098
ER
PT J
AU Tejeda, HA
O'Donnell, P
AF Tejeda, Hugo A.
O'Donnell, Patricio
TI Amygdala Inputs to the Prefrontal Cortex Elicit Heterosynaptic
Suppression of Hippocampal Inputs
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
DE amygdala; electrophysiology; in vivo intracellular recording; prefrontal
cortex
ID FUNCTIONAL CONNECTIVITY; DECISION-MAKING; IN-VIVO; RAT; NEURONS;
EMOTION; DRIVE; PROJECTIONS; INHIBITION; MATURATION
AB Whereas cooperative communication between the hippocampus (HP) and prefrontal cortex (PFC) is critical for cognitive functions, an antagonistic relationship may exist between the basolateral amygdala (BLA) and PFC during emotional processing. As PFC neurons integrate information from converging excitatory BLA and HP inputs, weexplored whether the ability of BLA inputs to evoke feedforward inhibition in the PFC affects converging HP synaptic inputs using in vivo intracellular recordings in anesthetized rats. BLA train stimulation decreased HP synaptic responses in the PFC in vivo. This effect was dependent on the timing of HP-evoked responses and the strength of BLA activation. BLA train stimulation also produced heterosynaptic suppression of responses from the amygdalo-piriform cortex, an associative temporal cortical structure. Heterosynaptic suppression was unidirectional as HP trains failed to modify BLA synaptic responses. These findings provide a mechanism by which BLA activation could decrease PFC neural activity and transiently attenuate the HP influence on PFC function.
C1 [Tejeda, Hugo A.; O'Donnell, Patricio] Univ Maryland, Sch Med, Dept Anat & Neurobiol, Baltimore, MD 21201 USA.
[Tejeda, Hugo A.] Univ Maryland, Sch Med, Program Neurosci, NIH,Grad Partnership Program, Baltimore, MD 21201 USA.
[O'Donnell, Patricio] Univ Maryland, Sch Med, Dept Psychiat, Baltimore, MD 21201 USA.
RP Tejeda, HA (reprint author), NIDA, 251 Bayview Blvd,Room 05A311, Baltimore, MD 21224 USA.
EM tejedah@nida.nih.gov; patricio.odonnell@pfizer.com
FU National Institutes of Health [R01 MH057683]
FX This work was supported by National Institutes of Health Grant R01
MH057683 to P.O. We thank Dr. Karl Deisseroth for the generous donation
of the adeno-associated virus CaMKII-CHR2 construct for the optogenetics
part of the study.
NR 35
TC 2
Z9 2
U1 0
U2 6
PU SOC NEUROSCIENCE
PI WASHINGTON
PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA
SN 0270-6474
J9 J NEUROSCI
JI J. Neurosci.
PD OCT 22
PY 2014
VL 34
IS 43
BP 14365
EP 14374
DI 10.1523/JNEUROSCI.0837-14.2014
PG 10
WC Neurosciences
SC Neurosciences & Neurology
GA AR5YM
UT WOS:000343658100020
PM 25339749
ER
PT J
AU McNeil, BK
Sorbellini, M
Grubb, RL
Apolo, AB
Cecchi, F
Athauda, G
Cohen, B
Giubellino, A
Simpson, H
Agarwal, PK
Coleman, J
Getzenberg, RH
Netto, GJ
Shih, J
Linehan, WM
Pinto, PA
Bottaro, DP
AF McNeil, Brian K.
Sorbellini, Maximiliano
Grubb, Robert L., III
Apolo, Andrea B.
Cecchi, Fabiola
Athauda, Gagani
Cohen, Benjamin
Giubellino, Alessio
Simpson, Haley
Agarwal, Piyush K.
Coleman, Jonathan
Getzenberg, Robert H.
Netto, George J.
Shih, Joanna
Linehan, W. Marston
Pinto, Peter A.
Bottaro, Donald P.
TI Preliminary evaluation of urinary soluble Met as a Biomarker for
urothelial carcinoma of the bladder
SO JOURNAL OF TRANSLATIONAL MEDICINE
LA English
DT Article
DE Urothelial carcinoma; Bladder cancer; Biomarker; HGF receptor; Met;
Urine
ID HGF/MET SIGNALING PATHWAY; C-MET; GROWTH-FACTOR; FOLLOW-UP; CANCER;
SURVIVAL; DIAGNOSIS; CELLS
AB Background: Among genitourinary malignancies, bladder cancer (BCa) ranks second in both prevalence and cause of death. Biomarkers of BCa for diagnosis, prognosis and disease surveillance could potentially help prevent progression, improve survival rates and reduce health care costs. Among several oncogenic signaling pathways implicated in BCa progression is that of hepatocyte growth factor (HGF) and its cell surface receptor, Met, now targeted by 25 experimental anti-cancer agents in human clinical trials. The involvement of this pathway in several cancers is likely to preclude the use of urinary soluble Met (sMet), which has been correlated with malignancy, for initial BCa screening. However, its potential utility as an aid to disease surveillance and to identify patients likely to benefit from HGF/Met-targeted therapies provide the rationale for this preliminary retrospective study comparing sMet levels between benign conditions and primary BCa, and in BCa cases, between different disease stages.
Methods: Normally voided urine samples were collected from patients with BCa (Total: 183; pTa: 55, pTis: 62, pT1: 24, pT2: 42) and without BCa (Total: 83) on tissue-procurement protocols at three institutions and sMet was measured and normalized to urinary creatinine. Normalized sMet values grouped by pathologic stage were compared using non-parametric tests for correlation and significant difference. ROC analyses were used to derive classification models for patients with or without BCa and patients with or without muscle-invasive BCa (MIBCa or NMIBCa).
Results: Urinary sMet levels accurately distinguished patients with BCa from those without (p < 0.0001, area under the curve (AUC): 0.7008) with limited sensitivity (61%) and moderate specificity (76%), and patients with MIBCa (n = 42) from those with NMIBCa (n = 141; p < 0.0001, AUC: 0.8002) with moderate sensitivity and specificity (76% and 77%, respectively) and low false negative rate (8%).
Conclusions: Urinary sMet levels distinguish patients with BCa from those without, and patients with or without MIBCa, suggesting the potential utility of urinary sMet as a BCa biomarker for surveillance following initial treatment. Further studies are warranted to determine its potential value for prognosis in advanced disease, predicting treatment response, or identifying patients likely to benefit from Met-targeted therapies.
C1 [McNeil, Brian K.; Sorbellini, Maximiliano; Cecchi, Fabiola; Athauda, Gagani; Cohen, Benjamin; Giubellino, Alessio; Simpson, Haley; Agarwal, Piyush K.; Coleman, Jonathan; Linehan, W. Marston; Pinto, Peter A.; Bottaro, Donald P.] NCI, Urol Oncol Branch, Ctr Canc Res, Hatfield Clin Res Ctr, Bethesda, MD 20892 USA.
[Grubb, Robert L., III] Washington Univ, Div Urol, St Louis, MO USA.
[Apolo, Andrea B.] NCI, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Getzenberg, Robert H.; Netto, George J.] Johns Hopkins Univ, Sch Med, Brady Urol Inst, Baltimore, MD USA.
[Netto, George J.] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA.
[Shih, Joanna] NCI, Biometr Res Branch, Div Canc Diag & Treatment, Rockville, MD USA.
RP Bottaro, DP (reprint author), NCI, Urol Oncol Branch, Ctr Canc Res, Hatfield Clin Res Ctr, Bldg 10,Rm 2 W-3952 10 Ctr Dr MSC 1210, Bethesda, MD 20892 USA.
EM don.bottaro@nih.gov
OI Bottaro, Donald/0000-0002-5057-5334; Coleman,
Jonathan/0000-0002-6428-7835
FU NIH, National Cancer Institute, Center for Cancer Research
FX This research was supported by the Intramural Research Program of the
NIH, National Cancer Institute, Center for Cancer Research.
NR 28
TC 4
Z9 4
U1 0
U2 0
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 OCT 21
PY 2014
VL 12
AR 199
DI 10.1186/1479-5876-12-199
PG 6
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA AT8DZ
UT WOS:000345165400001
PM 25335552
ER
PT J
AU Senni, M
Paulus, WJ
Gavazzi, A
Fraser, AG
Diez, J
Solomon, SD
Smiseth, OA
Guazzi, M
Lam, CSP
Maggioni, AP
Tschope, C
Metra, M
Hummel, SL
Edelmann, F
Ambrosio, G
Coats, AJS
Filippatos, GS
Gheorghiade, M
Anker, SD
Levy, D
Pfeffer, MA
Stough, WG
Pieske, BM
AF Senni, Michele
Paulus, Walter J.
Gavazzi, Antonello
Fraser, Alan G.
Diez, Javier
Solomon, Scott D.
Smiseth, Otto A.
Guazzi, Marco
Lam, Carolyn S. P.
Maggioni, Aldo P.
Tschoepe, Carsten
Metra, Marco
Hummel, Scott L.
Edelmann, Frank
Ambrosio, Giuseppe
Coats, Andrew J. Stewart
Filippatos, Gerasimos S.
Gheorghiade, Mihai
Anker, Stefan D.
Levy, Daniel
Pfeffer, Marc A.
Stough, Wendy Gattis
Pieske, Burkert M.
TI New strategies for heart failure with preserved ejection fraction: the
importance of targeted therapies for heart failure phenotypes
SO EUROPEAN HEART JOURNAL
LA English
DT Review
DE Heart failure, Diastolic; Clinical trial; Diabetes mellitus; Exercise
tolerance; Phenotype; Preserved ejection fraction
ID LEFT-VENTRICULAR HYPERTROPHY; RANDOMIZED CLINICAL-TRIAL; COLLAGEN
TYPE-I; ANGIOTENSIN-ALDOSTERONE SYSTEM; BUNDLE-BRANCH-BLOCK; LATE SODIUM
CURRENT; LOW-SALT DIET; DIASTOLIC FUNCTION; EXERCISE CAPACITY;
PULMONARY-HYPERTENSION
AB The management of heart failure with reduced ejection fraction (HF-REF) has improved significantly over the last two decades. In contrast, little or no progress has been made in identifying evidence-based, effective treatments for heart failure with preserved ejection fraction (HF-PEF). Despite the high prevalence, mortality, and cost of HF-PEF, large phase III international clinical trials investigating interventions to improve outcomes in HF-PEF have yielded disappointing results. Therefore, treatment of HF-PEF remains largely empiric, and almost no acknowledged standards exist. There is no single explanation for the negative results of past HF-PEF trials. Potential contributors include an incomplete understanding of HF-PEF pathophysiology, the heterogeneity of the patient population, inadequate diagnostic criteria, recruitment of patients without true heart failure or at early stages of the syndrome, poor matching of therapeutic mechanisms and primary pathophysiological processes, suboptimal study designs, or inadequate statistical power. Many novel agents are in various stages of research and development for potential use in patients with HF-PEF. To maximize the likelihood of identifying effective therapeutics for HF-PEF, lessons learned from the past decade of research should be applied to the design, conduct, and interpretation of future trials. This paper represents a synthesis of a workshop held in Bergamo, Italy, and it examines new and emerging therapies in the context of specific, targeted HF-PEF phenotypes where positive clinical benefit may be detected in clinical trials. Specific considerations related to patient and endpoint selection for future clinical trials design are also discussed.
C1 [Senni, Michele; Gavazzi, Antonello] Hosp Papa Giovanni XXIII, Cardiovasc Dept, Bergamo, Italy.
[Paulus, Walter J.] VU Univ Med Ctr Amsterdam, Inst Cardiovasc Res, Amsterdam, Netherlands.
[Fraser, Alan G.] Cardiff Univ, Wales Heart Res Inst, Cardiff CF10 3AX, S Glam, Wales.
[Diez, Javier] Univ Navarra, Univ Navarra Clin, Ctr Appl Med Res, Div Cardiovasc Sci, E-31080 Pamplona, Spain.
[Diez, Javier] Univ Navarra, Univ Navarra Clin, Dept Cardiol & Cardiac Surg, E-31080 Pamplona, Spain.
[Solomon, Scott D.; Pfeffer, Marc A.] Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA.
[Solomon, Scott D.; Pfeffer, Marc A.] Harvard Univ, Sch Med, Boston, MA USA.
[Smiseth, Otto A.] Univ Oslo, Inst Surg Res, Dept Cardiol, Oslo, Norway.
[Smiseth, Otto A.] Univ Oslo, Ctr Cardiol Innovat, Oslo, Norway.
[Guazzi, Marco] Univ Milan, IRCCS Policlin San Donato, Dept Biomed Sci Hlth, Heart Failure Unit, Milan, Italy.
[Lam, Carolyn S. P.] Natl Univ Hlth Syst, Singapore, Singapore.
[Maggioni, Aldo P.] ANMCO Res Ctr, Florence, Italy.
[Tschoepe, Carsten] Charite Univ Med Berlin, Campus Benjamin Franklin, Dept Cardiol & Pneumol, Berlin, Germany.
[Metra, Marco] Univ Brescia, Dept Expt & Appl Med, Brescia, Italy.
[Hummel, Scott L.] Univ Michigan, Dept Internal Med, Div Cardiovasc Med, Ann Arbor, MI 48109 USA.
[Hummel, Scott L.] Ann Arbor Vet Affairs Med Ctr, Cardiol Sect, Ann Arbor, MI USA.
[Edelmann, Frank] Univ Gottingen, Dept Cardiol & Pneumol, D-37073 Gottingen, Germany.
[Ambrosio, Giuseppe] Univ Perugia, Sch Med, Div Cardiol, I-06100 Perugia, Italy.
[Coats, Andrew J. Stewart] Monash Univ, Melbourne, Vic 3004, Australia.
[Coats, Andrew J. Stewart] Univ Warwick, Coventry CV4 7AL, W Midlands, England.
[Filippatos, Gerasimos S.] Univ Athens, Hosp Attikon, Athens, Greece.
[Gheorghiade, Mihai] Northwestern Univ, Feinberg Sch Med, Ctr Cardiovasc Innovat, Chicago, IL 60611 USA.
[Anker, Stefan D.] Univ Med Ctr Gottingen, Dept Innovat Clin Trials, Gottingen, Germany.
[Anker, Stefan D.] Charite, Dept Cardiol, Berlin, Germany.
[Levy, Daniel] Framingham Heart Dis Epidemiol Study, Framingham, MA USA.
[Levy, Daniel] Boston Univ, Sch Med, Div Cardiol, Boston, MA 02118 USA.
[Levy, Daniel] NHLBI, Ctr Populat Studies, Bethesda, MD 20892 USA.
[Stough, Wendy Gattis] Campbell Univ, Coll Pharm & Hlth Sci, Dept Clin Res, Buies Creek, NC 27506 USA.
[Pieske, Burkert M.] Med Univ Graz, Ludwig Boltzmann Inst Heart Failure Res, Dept Cardiol, A-8010 Graz, Austria.
RP Pieske, BM (reprint author), Med Univ Graz, Ludwig Boltzmann Inst Heart Failure Res, Dept Cardiol, Auenbruggerpl 15, A-8010 Graz, Austria.
EM burkert.pieske@medunigraz.at
RI Lainscak, Mitja/F-3237-2015; Guazzi, Marco/J-3165-2016; Stough,
Wendy/R-4287-2016; Diez, Javier/D-7014-2017;
OI Guazzi, Marco/0000-0002-8456-609X; Stough, Wendy/0000-0001-8290-1205;
Maggioni, Aldo Pietro/0000-0003-2764-6779; Diez,
Javier/0000-0002-3414-6919; Metra, Marco/0000-0001-6691-8568
FU Fondazione Internazionale Menarini, Milan, Italy; NIH/NHLBI
[K23HL109176]
FX The workshop was supported by an unrestricted grant from Fondazione
Internazionale Menarini, Milan, Italy. Dr Scott Hummel's contributions
to the article were supported by a K23 grant from NIH/NHLBI
(K23HL109176).
NR 179
TC 69
Z9 69
U1 7
U2 30
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0195-668X
EI 1522-9645
J9 EUR HEART J
JI Eur. Heart J.
PD OCT 21
PY 2014
VL 35
IS 40
SI SI
BP 2797
EP 2811
DI 10.1093/eurheartj/ehu204
PG 20
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA AR7CE
UT WOS:000343736700009
PM 25104786
ER
PT J
AU Nie, LM
Chen, XY
AF Nie, Liming
Chen, Xiaoyuan
TI Structural and functional photoacoustic molecular tomography aided by
emerging contrast agents
SO CHEMICAL SOCIETY REVIEWS
LA English
DT Review
ID MULTISPECTRAL OPTOACOUSTIC TOMOGRAPHY; SENTINEL LYMPH-NODES; COPPER
SULFIDE NANOPARTICLES; OPTICAL COHERENCE TOMOGRAPHY; GREEN FLUORESCENT
PROTEIN; WALLED CARBON NANOTUBES; BLOOD-OXYGEN SATURATION; BRAIN-TUMOR
DELINEATION; NEAR-INFRARED LIGHT; IN-VIVO
AB Photoacoustic tomography (PAT) can offer structural, functional and molecular contrasts at scalable observation level. By ultrasonically overcoming the strong optical scattering, this imaging technology can reach centimeters penetration depth while retaining high spatial resolution in biological tissue. Recent extensive research has been focused on developing new contrast agents to improve the imaging sensitivity, specificity and efficiency. These emerging materials have substantially accelerated PAT applications in signal sensing, functional imaging, biomarker labeling and therapy monitoring etc. Here, the potentials of different optical probes as PAT contrast agents were elucidated. We first describe the instrumental embodiments and the measured functional parameters, then focus on emerging contrast agent-based PAT applications, and finally discuss the challenges and prospects.
C1 [Nie, Liming; Chen, Xiaoyuan] Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed LOMIN, NIH, Bethesda, MD 20892 USA.
[Nie, Liming] Xiamen Univ, Sch Publ Hlth, Ctr Mol Imaging & Translat Med, State Key Lab Mol Vaccinol & Mol Diagnost, Xiamen 361102, Peoples R China.
RP Chen, XY (reprint author), Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed LOMIN, NIH, Bethesda, MD 20892 USA.
EM shawn.chen@nih.gov
RI Nie, Liming/F-7718-2016
FU National Intramural Research Program (IRP) of the National Institute of
Biomedical Imaging and Bioengineering (NIBIB), NIH
FX This work was supported by National Intramural Research Program (IRP) of
the National Institute of Biomedical Imaging and Bioengineering (NIBIB),
NIH.
NR 240
TC 75
Z9 75
U1 16
U2 153
PU ROYAL SOC CHEMISTRY
PI CAMBRIDGE
PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS,
ENGLAND
SN 0306-0012
EI 1460-4744
J9 CHEM SOC REV
JI Chem. Soc. Rev.
PD OCT 21
PY 2014
VL 43
IS 20
BP 7132
EP 7170
DI 10.1039/c4cs00086b
PG 39
WC Chemistry, Multidisciplinary
SC Chemistry
GA AQ5WT
UT WOS:000342880000012
PM 24967718
ER
PT J
AU Sandrini, M
Brambilla, M
Manenti, R
Rosini, S
Cohen, LG
Cotelli, M
AF Sandrini, Marco
Brambilla, Michela
Manenti, Rosa
Rosini, Sandra
Cohen, Leonardo G.
Cotelli, Maria
TI Noninvasive stimulation of prefrontal cortex strengthens existing
episodic memories and reduces forgetting in the elderly
SO FRONTIERS IN AGING NEUROSCIENCE
LA English
DT Article
DE tDCS; aging; reconsolidation; episodic memory; prefrontal cortex;
memory; enhancement; forgetting
ID TRANSCRANIAL MAGNETIC STIMULATION; LONG-TERM-MEMORY; DECLARATIVE MEMORY;
BRAIN-STIMULATION; ENHANCES RECONSOLIDATION; HEALTHY-SUBJECTS; FEAR
MEMORIES; CONSOLIDATION; HUMANS; RETRIEVAL
AB Memory consolidation is a dynamic process. Reactivation of consolidated memories by a reminder triggers reconsolidation, a time-limited period during which existing memories can be modified (i.e., weakened or strengthened). Episodic memory refers to our ability to recall specific past events about what happened, including where and when. Difficulties in this form of long-term memory commonly occur in healthy aging. Because episodic memory is critical for daily life functioning, the development of effective interventions to reduce memory loss in elderly individuals is of great importance. Previous studies in young adults showed that the dorsolateral prefrontal cortex (DLPFC) plays a causal role in strengthening of verbal episodic memories through reconsolidation. The aim of the present study was to explore the extent to which facilitatory transcranial direct current stimulation (anodal tDCS) over the left DLPFC would strengthen existing episodic memories through reconsolidation in elderly individuals. On Day 1, older adults learned a list of 20 words. On Day 2 (24 h later), they received a reminder or not, and after 10 min tDCS was applied over the left DLPFC. Memory recall was tested on Day 3 (48 h later) and Day 30 (1 month later). Surprisingly, anodal tDCS over the left DLPFC (i.e., with or without the reminder) strengthened existing verbal episodic memories and reduced forgetting compared to sham stimulation. These results provide a framework for testing the hypothesis that facilitatory tDCS of left DLPFC might strengthen existing episodic memories and reduce memory loss in older adults with amnestic mild cognitive impairment
C1 [Sandrini, Marco; Cohen, Leonardo G.] NINDS, Human Cort Physiol & Neurorehabilitat Sect, NIH, Bethesda, MD 20892 USA.
[Sandrini, Marco] Uniformed Serv Univ Hlth Sci, Ctr Neurosci & Regenerat Med, Bethesda, MD 20814 USA.
[Brambilla, Michela; Manenti, Rosa; Rosini, Sandra; Cotelli, Maria] IRCCS Ist Ctr San Giovanni di Dio Fatebenefratell, Neuropsychol Unit, Brescia, Italy.
RP Sandrini, M (reprint author), NINDS, Human Cort Physiol & Neurorehabilitat Sect, NIH, Bldg 10,Room 7D52, Bethesda, MD 20892 USA.
EM marco.sandrini@nih.gov
RI Brambilla, Michela/J-2288-2016; Manenti, Rosa/J-7656-2016; Cotelli,
Maria/K-1355-2016; Sandrini, Marco/J-2276-2014; Rosini,
Sandra/E-9480-2017
OI Brambilla, Michela/0000-0003-0761-2037; Manenti,
Rosa/0000-0002-5955-2323; Cotelli, Maria/0000-0003-3208-3798; Sandrini,
Marco/0000-0002-1664-5722; Rosini, Sandra/0000-0002-8207-960X
FU United States Department of Defense in the Center for Neuroscience and
Regenerative Medicine (CNRM)
FX This work was partially supported by funding from United States
Department of Defense in the Center for Neuroscience and Regenerative
Medicine (CNRM) to Marco Sandrini. The authors are indebted with
Clarissa Ferrari for assistance in the statistical analysis.
NR 83
TC 18
Z9 18
U1 3
U2 39
PU FRONTIERS RESEARCH FOUNDATION
PI LAUSANNE
PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND
SN 1663-4365
J9 FRONT AGING NEUROSCI
JI Front. Aging Neurosci.
PD OCT 20
PY 2014
VL 6
AR 289
DI 10.3389/fnagi.2014.00289
PG 9
WC Geriatrics & Gerontology; Neurosciences
SC Geriatrics & Gerontology; Neurosciences & Neurology
GA AY9ME
UT WOS:000347874400001
PM 25368577
ER
PT J
AU Dema, B
Charles, N
Pellefigues, C
Ricks, TK
Suzuki, R
Jiang, C
Scheffel, J
Hasni, S
Hoffman, V
Jablonski, M
Sacre, K
Gobert, D
Papo, T
Daugas, E
Crampton, S
Bolland, S
Rivera, J
AF Dema, Barbara
Charles, Nicolas
Pellefigues, Christophe
Ricks, Tiffany K.
Suzuki, Ryo
Jiang, Chao
Scheffel, Jorg
Hasni, Sarfaraz
Hoffman, Victoria
Jablonski, Mathieu
Sacre, Karim
Gobert, Delphine
Papo, Thomas
Daugas, Eric
Crampton, Steve
Bolland, Silvia
Rivera, Juan
TI Immunoglobulin E plays an immunoregulatory role in lupus
SO JOURNAL OF EXPERIMENTAL MEDICINE
LA English
DT Article
ID FC-GAMMA-RIIB; DEFICIENT MICE; CELL ACTIVATION; IGE; EXPRESSION;
BASOPHILS; PROLIFERATION; PATHOGENESIS; ALLERGY; MARKER
AB The (patho) physiological role of IgE in nonallergic inflammatory diseases is not well understood. Here, we explored the effect of IgE deficiency on the inflammatory response in Fc gamma RIIB-deficient mice as well as in mice carrying both a deletion of Fc gamma RIIB and the chromosomal translocation of Y-linked autoimmune acceleration (Yaa) that hastens and results in a more aggressive lupuslike disease in these mice. The findings show that deficiency of IgE delays disease development and severity as demonstrated by reduced autoantibody production and amelioration of organ pathologies. This was associated with decreased numbers of plasma cells and reduced levels of IgG2b and IgG3. Unexpectedly, the loss of IgE also caused a striking decrease of immune cell infiltration in secondary lymphoid organs with a marked effect on the presence of dendritic cells, monocytes, neutrophils, and eosinophils in these organs and decreased activation of basophils. The presence of autoreactive IgE in human systemic lupus erythematosus subjects was also associated with increased basophil activation and enhanced disease activity. These findings argue that IgE facilitates the amplification of autoimmune inflammation.
C1 [Dema, Barbara; Ricks, Tiffany K.; Suzuki, Ryo; Jiang, Chao; Scheffel, Jorg; Rivera, Juan] NIAMSD, Mol Immunol Sect, Immunogenet Mol Lab, NIH, Bethesda, MD 20892 USA.
[Hasni, Sarfaraz] NIAMSD, Off Clin Director, NIH, Bethesda, MD 20892 USA.
[Hoffman, Victoria] NIAID, Diagnost & Res Serv Branch, Off Director, NIH, Bethesda, MD 20892 USA.
[Crampton, Steve; Bolland, Silvia] NIAID, Autoimmun & Funct Genom Sect, Immunogenet Lab, NIH, Bethesda, MD 20892 USA.
[Dema, Barbara; Charles, Nicolas; Pellefigues, Christophe; Sacre, Karim; Papo, Thomas; Daugas, Eric] Univ Paris Diderot, DHU FIRE, Ctr Rech Inflammat, Lab Excellence Inflamex,CNRS ERL8252,INSERM UMR11, F-75018 Paris, France.
[Jablonski, Mathieu; Daugas, Eric] Univ Paris Diderot, Hop Bichat, AP HP, Fac Med Site Bichat,Dept Nephrol, F-75018 Paris, France.
[Sacre, Karim; Gobert, Delphine; Papo, Thomas] Univ Paris Diderot, Hop Bichat, AP HP, Fac Med,Dept Internal Med, F-75018 Paris, France.
RP Rivera, J (reprint author), NIAMSD, Mol Immunol Sect, Immunogenet Mol Lab, NIH, Bethesda, MD 20892 USA.
EM juan_rivera@nih.gov
RI Charles, Nicolas/P-5430-2014
OI Charles, Nicolas/0000-0002-5416-5834
FU Intramural Research Program of NIAMS; NIAID, NIH; French Institut
National de la Sante Et de la Recherche Medicale (INSERM); Assistance
Publique - Hopitaux de Paris (AP-HP); Mairie de Paris (Emergences), ANR
JCJC SVSE1 BASILE; French Kidney Foundation (Fondation du Rein);
Laboratoire d'excellence INFLAMEX; Laboratory Animal Care and Use, Flow
Cytometry, and Light Imaging Sections of the Office of Science and
Technology, NIAMS
FX This research was supported by the Intramural Research Program of NIAMS
and NIAID, NIH, by the French Institut National de la Sante Et de la
Recherche Medicale (INSERM), by the Assistance Publique - Hopitaux de
Paris (AP-HP), and by grants from the Mairie de Paris (Emergences 2010),
ANR JCJC SVSE1 2011 BASILE and the French Kidney Foundation (Fondation
du Rein) to N. Charles. N. Charles and B. Dema are supported by the
Laboratoire d'excellence INFLAMEX. We acknowledge the support of the
Laboratory Animal Care and Use, Flow Cytometry, and Light Imaging
Sections of the Office of Science and Technology, NIAMS.
NR 19
TC 26
Z9 26
U1 1
U2 8
PU ROCKEFELLER UNIV PRESS
PI NEW YORK
PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA
SN 0022-1007
EI 1540-9538
J9 J EXP MED
JI J. Exp. Med.
PD OCT 20
PY 2014
VL 211
IS 11
BP 2159
EP 2168
DI 10.1084/jem.20140066
PG 10
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA AT9TK
UT WOS:000345268700004
PM 25267791
ER
PT J
AU Carotta, S
Willis, SN
Hasbold, J
Inouye, M
Pang, SHM
Emslie, D
Light, A
Chopin, M
Shi, W
Wang, HS
Morse, HC
Tarlinton, DM
Corcoran, LM
Hodgkin, PD
Nutt, SL
AF Carotta, Sebastian
Willis, Simon N.
Hasbold, Jhagvaral
Inouye, Michael
Pang, Swee Heng Milon
Emslie, Dianne
Light, Amanda
Chopin, Michael
Shi, Wei
Wang, Hongsheng
Morse, Herbert C., III
Tarlinton, David M.
Corcoran, Lynn M.
Hodgkin, Philip D.
Nutt, Stephen L.
TI The transcription factors IRF8 and PU.1 negatively regulate plasma cell
differentiation
SO JOURNAL OF EXPERIMENTAL MEDICINE
LA English
DT Article
ID GENE-EXPRESSION PROGRAM; GERMINAL CENTER B; LYMPHOCYTE DIFFERENTIATION;
CLASS-SWITCH; MATURE B; RNA-SEQ; SPI-B; BLIMP-1; NETWORK; BCL-6
AB Activated B cells undergo immunoglobulin class-switch recombination (CSR) and differentiate into antibody-secreting plasma cells. The distinct transcriptomes of B cells and plasma cells are maintained by the antagonistic influences of two groups of transcription factors: those that maintain the B cell program, including BCL6 and PAX5, and plasma cell-promoting factors, such as IRF4 and BLIMP-1. We show that the complex of IRF8 and PU.1 controls the propensity of B cells to undergo CSR and plasma cell differentiation by concurrently promoting the expression of BCL6 and PAX5 and repressing AID and BLIMP-1. As the PU.1-IRF8 complex functions in a reciprocal manner to IRF4, we propose that concentration-dependent competition between these factors controls B cell terminal differentiation.
C1 [Carotta, Sebastian; Willis, Simon N.; Hasbold, Jhagvaral; Inouye, Michael; Pang, Swee Heng Milon; Emslie, Dianne; Light, Amanda; Chopin, Michael; Shi, Wei; Tarlinton, David M.; Corcoran, Lynn M.; Hodgkin, Philip D.; Nutt, Stephen L.] Royal Melbourne Hosp, Walter & Eliza Hall Inst Med Res, Parkville, Vic 3050, Australia.
[Carotta, Sebastian; Willis, Simon N.; Hasbold, Jhagvaral; Pang, Swee Heng Milon; Chopin, Michael; Tarlinton, David M.; Corcoran, Lynn M.; Hodgkin, Philip D.; Nutt, Stephen L.] Univ Melbourne, Dept Med Biol, Parkville, Vic 3010, Australia.
[Inouye, Michael] Univ Melbourne, Dept Pathol, Parkville, Vic 3010, Australia.
[Inouye, Michael] Univ Melbourne, Dept Microbiol & Immunol, Parkville, Vic 3010, Australia.
[Shi, Wei] Univ Melbourne, Dept Comp & Informat Syst, Parkville, Vic 3010, Australia.
[Wang, Hongsheng; Morse, Herbert C., III] NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA.
RP Nutt, SL (reprint author), Royal Melbourne Hosp, Walter & Eliza Hall Inst Med Res, Parkville, Vic 3050, Australia.
EM nutt@wehi.edu.au
OI Morse, Herbert/0000-0002-9331-3705; Nutt, Stephen/0000-0002-0020-6637
FU National Health and Medical Research Council (NHMRC) of Australia
[575500, APP1054925]; Victorian State Government Operational
Infrastructure Support; Australian Government NHMRC IRIIS; Intramural
Research Program of the National Institutes of Health, National
Institute of Allergy and Infectious Diseases; NHMRC; Leukaemia
Foundation; Australian Research Council Future Fellowship
FX This work was supported by a National Health and Medical Research
Council (NHMRC) of Australia Program grant (575500 and APP1054925 to D.
M. Tarlinton, L. M. Corcoran, P. D. Hodgkin, and S. L. Nutt), Victorian
State Government Operational Infrastructure Support, Australian
Government NHMRC IRIIS, and the Intramural Research Program of the
National Institutes of Health, National Institute of Allergy and
Infectious Diseases (to H. C. Morse III). S. Carotta was supported by an
NHMRC Career Development Award, S. H. M. Pang by the Leukaemia
Foundation, M. Inouye and S.N. Willis by NHMRC Post-doctoral
Fellowships, S. L. Nutt by an Australian Research Council Future
Fellowship, and D. M. Tarlinton, L. M. Corcoran, and P. D. Hodgkin by
NHMRC Research Fellowships.
NR 65
TC 23
Z9 23
U1 1
U2 7
PU ROCKEFELLER UNIV PRESS
PI NEW YORK
PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA
SN 0022-1007
EI 1540-9538
J9 J EXP MED
JI J. Exp. Med.
PD OCT 20
PY 2014
VL 211
IS 11
BP 2169
EP 2181
DI 10.1084/jem.20140425
PG 13
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA AT9TK
UT WOS:000345268700005
PM 25288399
ER
PT J
AU Maul, RW
Cao, Z
Venkataraman, L
Giorgetti, CA
Press, JL
Denizot, Y
Du, HS
Sen, RJ
Gearhart, PJ
AF Maul, Robert W.
Cao, Zheng
Venkataraman, Lakshmi
Giorgetti, Carol A.
Press, Joan L.
Denizot, Yves
Du, Hansen
Sen, Ranjan
Gearhart, Patricia J.
TI Spt5 accumulation at variable genes distinguishes somatic hypermutation
in germinal center B cells from ex vivo-activated cells
SO JOURNAL OF EXPERIMENTAL MEDICINE
LA English
DT Article
ID RNA-POLYMERASE-II; CLASS SWITCH RECOMBINATION; INDUCED CYTIDINE
DEAMINASE; SINGLE-STRANDED-DNA; IN-VIVO; MEMORY B; TRANSCRIPTIONAL
ELONGATION; IMMUNOGLOBULIN GENES; INTRONIC ENHANCER; REGION
AB Variable (V) genes of immunoglobulins undergo somatic hypermutation by activation-induced deaminase (AID) to generate amino acid substitutions that encode antibodies with increased affinity for antigen. Hypermutation is restricted to germinal center B cells and cannot be recapitulated in ex vivo-activated splenic cells, even though the latter express high levels of AID. This suggests that there is a specific feature of antigen activation in germinal centers that recruits AID to V genes which is absent in mitogen-activated cultured cells. Using two Igh knock-in mouse models, we found that RNA polymerase II accumulates in V regions in B cells after both types of stimulation for an extended distance of 1.2 kb from the TATA box. The paused polymerases generate abundant single-strand DNA targets for AID. However, there is a distinct accumulation of the initiating form of polymerase, along with the transcription cofactor Spt5 and AID, in the V region from germinal center cells, which is totally absent in cultured cells. These data support a model where mutations are prevalent in germinal center cells, but not in ex vivo cells, because the initiating form of polymerase is retained, which affects Spt5 and AID recruitment.
C1 [Maul, Robert W.; Cao, Zheng; Du, Hansen; Sen, Ranjan; Gearhart, Patricia J.] NIA, Lab Mol Biol & Immunol, NIH, Baltimore, MD 21224 USA.
[Venkataraman, Lakshmi; Giorgetti, Carol A.; Press, Joan L.] Brandeis Univ, Dept Biol, Waltham, MA 02454 USA.
[Denizot, Yves] Univ Limoges, CNRS, UMR 7276, F-87025 Limoges, France.
RP Gearhart, PJ (reprint author), NIA, Lab Mol Biol & Immunol, NIH, Baltimore, MD 21224 USA.
EM gearhartp@mail.nih.gov
RI Denizot, Yves Pierre/H-9769-2016
FU Intramural Research Program of the National Institutes of Health (NIH),
National Institute on Aging; NIH [AI13725]; American Cancer Society
FX This research was supported in part by the Intramural Research Program
of the National Institutes of Health (NIH), National Institute on Aging,
and by grants from the NIH (AI13725 to J.L. Press) and the American
Cancer Society (L. Venkataraman).
NR 55
TC 10
Z9 10
U1 1
U2 3
PU ROCKEFELLER UNIV PRESS
PI NEW YORK
PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA
SN 0022-1007
EI 1540-9538
J9 J EXP MED
JI J. Exp. Med.
PD OCT 20
PY 2014
VL 211
IS 11
BP 2297
EP 2306
DI 10.1084/jem.20131512
PG 10
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA AT9TK
UT WOS:000345268700013
PM 25288395
ER
PT J
AU Wei, YM
Yang, HX
Zhu, WW
Yang, HY
Li, HX
Yan, J
Zhang, CL
AF Wei Yumei
Yang Huixia
Zhu Weiwei
Yang Hongyun
Li Haixia
Yan Jie
Zhang Cuilin
TI International Association of Diabetes and Pregnancy Study Group criteria
is suitable for gestational diabetes mellitus diagnosis: further
evidence from China
SO CHINESE MEDICAL JOURNAL
LA English
DT Article
DE gestational diabetes mellitus; macrosomia; cesarean section; neonatal
hypoglycemia
ID GLUCOSE-TOLERANCE TEST; WOMEN; CLASSIFICATION; HYPERGLYCEMIA; TESTS;
75-G
AB Background The International Association of Diabetes and Pregnancy Study Group (IADPSG) recommended new diagnostic criteria for gestational diabetes mellitus (GDM) after extensive analyses of the Hyperglycemia and Adverse Pregnancy Outcomes (HAPO) study. Unfortunately, there was no data from mainland of China in this study. We evaluated the feasibility of IADPSG criteria for GDM diagnosis in China.
Methods A large prospective study was conducted. We reviewed medical records of a total of 25 674 pregnant women who underwent GDM screening and diagnosis between January 1, 2005 and December 31, 2012 in the Peking University First Hospital. The prevalence of gestational glucose metabolism abnormalities was calculated according to different cut off values defined by the National Diabetes Data Group (NDDG) or the IADPSG, and the incidence of adverse pregnancy outcomes related to GDM was analyzed.
Results According to the cut off values of NDDG and IADPSG criteria, the prevalence of gestational glucose metabolism abnormalities was 8.4% and 18.9% (P<0.01) respectively, and the prevalence of cesarean section (52.5% vs. 46.0%, P<0.01), macrosomia (7.5% vs. 6.3%, P<0.05), neonatal hypoglycemia (1.6% vs. 1.0%, P<0.01), and perinatal death (0.5% vs. 0.2%, P<0.01); the prevalence was significantly lower when IADPSG criteria were applied. The prevalence of macrosomia, cesarean section, neonatal hypoglycemia, pregnancy induced hypertension, etc. was also higher in the GDM group than in the normal group. The prevalence of cesarean section (62.3%) and nnacrosomia (14.8%) was the highest in untreated mild GDM patients.
Conclusions Our results indicated that treatment/intervention of women with GDM identified by IADPSG criteria was related to significantly lower risk of multiple adverse pregnancy outcomes. Such findings provide support for applying IADPSG criteria in China.
C1 [Wei Yumei; Yang Huixia; Zhu Weiwei; Yan Jie] Peking Univ, Hosp 1, Dept Obstet & Gynecol, Beijing 100034, Peoples R China.
[Yang Hongyun; Li Haixia] Peking Univ, Hosp 1, Dept Clin Lab, Beijing 100034, Peoples R China.
[Zhang Cuilin] NICHD, Div Epidemiol Stat & Prevent Res, NIH, Rockville, MD 20852 USA.
RP Yang, HX (reprint author), Peking Univ, Hosp 1, Dept Obstet & Gynecol, Beijing 100034, Peoples R China.
EM yanghuixia@bjmu.edu.cn
FU World Diabetes Foundation [WDF10-517]
FX This study was supported by the World Diabetes Foundation for funding
the GDM Project (No. WDF10-517).
NR 21
TC 12
Z9 14
U1 1
U2 5
PU CHINESE MEDICAL ASSOC
PI BEIJING
PA 42 DONGSI XIDAJIE, BEIJING 100710, PEOPLES R CHINA
SN 0366-6999
J9 CHINESE MED J-PEKING
JI Chin. Med. J.
PD OCT 20
PY 2014
VL 127
IS 20
BP 3553
EP 3556
DI 10.3760/cma.j.issn.0366-6999.20140898
PG 4
WC Medicine, General & Internal
SC General & Internal Medicine
GA AT1XK
UT WOS:000344724100007
PM 25316228
ER
PT J
AU O'Grady, TJ
Kitahara, CM
DiRienzo, AG
Gates, MA
AF O'Grady, Thomas J.
Kitahara, Cari M.
DiRienzo, A. Gregory
Gates, Margaret A.
TI The Association between Selenium and Other Micronutrients and Thyroid
Cancer Incidence in the NIH-AARP Diet and Health Study
SO PLOS ONE
LA English
DT Article
ID PROSPECTIVE COHORT; REGRESSION-MODELS; POOLED ANALYSIS; RISK-FACTORS;
PATTERNS; FOOD; SUPPLEMENTATION; ADULTS; WOMEN; FRUIT
AB Background: Selenium is an essential trace element that is important for thyroid hormone metabolism and has antioxidant properties which protect the thyroid gland from oxidative stress. The association of selenium, as well as intake of other micronutrients, with thyroid cancer is unclear.
Methods: We evaluated associations of dietary selenium, beta-carotene, calcium, vitamin D, vitamin C, vitamin E, folate, magnesium, and zinc intake with thyroid cancer risk in the National Institutes of Health - American Association of Retired Persons Diet and Health Study, a large prospective cohort of 566,398 men and women aged 50-71 years in 1995-1996. Multivariable-adjusted Cox proportional hazards regression was used to examine associations between dietary intake of micronutrients, assessed using a food frequency questionnaire, and thyroid cancer cases, ascertained by linkage to state cancer registries and the National Death Index.
Results: With the exception of vitamin C, which was associated with an increased risk of thyroid cancer (HRQ5 (vs Q1), 1.34; 95% CI, 1.02-1.76; P-trend, <0.01), we observed no evidence of an association between quintile of selenium (HRQ5 (vs Q1), 1.23; 95% CI, 0.92-1.65; P-trend, 0.26) or other micronutrient intake and thyroid cancer.
Conclusion: Our study does not suggest strong evidence for an association between dietary intake of selenium or other micronutrients and thyroid cancer risk. More studies are needed to clarify the role of selenium and other micronutrients in thyroid carcinogenesis.
C1 [O'Grady, Thomas J.; DiRienzo, A. Gregory; Gates, Margaret A.] SUNY Albany, Sch Publ Hlth, Rensselaer, NY USA.
[Kitahara, Cari M.] NCI, Div Canc Epidemiol & Genet, NIH, Rockville, MD USA.
RP O'Grady, TJ (reprint author), SUNY Albany, Sch Publ Hlth, Rensselaer, NY USA.
EM togrady@albany.edu
RI Kitahara, Cari/R-8267-2016
FU Intramural Research Program of the National Cancer Institute, National
Institutes of Health
FX This work was supported in part by the Intramural Research Program of
the National Cancer Institute, National Institutes of Health. The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript. The authors
received no other funding of any type for the preparation of this
manuscript.
NR 54
TC 3
Z9 4
U1 0
U2 13
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD OCT 20
PY 2014
VL 9
IS 10
AR e110886
DI 10.1371/journal.pone.0110886
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AS0AY
UT WOS:000343942100105
PM 25329812
ER
PT J
AU Primiani, CT
Ryan, VH
Rao, JS
Cam, MC
Ahn, K
Modi, HR
Rapoport, SI
AF Primiani, Christopher T.
Ryan, Veronica H.
Rao, Jagadeesh S.
Cam, Margaret C.
Ahn, Kwangmi
Modi, Hiren R.
Rapoport, Stanley I.
TI Coordinated Gene Expression of Neuroinflammatory and Cell Signaling
Markers in Dorsolateral Prefrontal Cortex during Human Brain Development
and Aging
SO PLOS ONE
LA English
DT Article
ID ARACHIDONIC-ACID CASCADE; TUMOR-NECROSIS-FACTOR; ALZHEIMERS-DISEASE
BRAIN; CENTRAL-NERVOUS-SYSTEM; HUMAN CEREBRAL-CORTEX; TOLL-LIKE
RECEPTORS; INNATE IMMUNITY; MICROGLIAL ACTIVATION; INFLAMMATORY
RESPONSE; TRANSCRIPTION FACTORS
AB Background: Age changes in expression of inflammatory, synaptic, and neurotrophic genes are not well characterized during human brain development and senescence. Knowing these changes may elucidate structural, metabolic, and functional brain processes over the lifespan, as well vulnerability to neurodevelopmental or neurodegenerative diseases. Hypothesis: Expression levels of inflammatory, synaptic, and neurotrophic genes in the human brain are coordinated over the lifespan and underlie changes in phenotypic networks or cascades.
Methods: We used a large-scale microarray dataset from human prefrontal cortex, BrainCloud, to quantify age changes over the lifespan, divided into Development (0 to 21 years, 87 brains) and Aging (22 to 78 years, 144 brains) intervals, in transcription levels of 39 genes.
Results: Gene expression levels followed different trajectories over the lifespan. Many changes were intercorrelated within three similar groups or clusters of genes during both Development and Aging, despite different roles of the gene products in the two intervals. During Development, changes were related to reported neuronal loss, dendritic growth and pruning, and microglial events; TLR4, IL1R1, NFKB1, MOBP, PLA2G4A, and PTGS2 expression increased in the first years of life, while expression of synaptic genes GAP43 and DBN1 decreased, before reaching plateaus. During Aging, expression was upregulated for potentially pro-inflammatory genes such as NFKB1, TRAF6, TLR4, IL1R1, TSPO, and GFAP, but downregulated for neurotrophic and synaptic integrity genes such as BDNF, NGF, PDGFA, SYN, and DBN1.
Conclusions: Coordinated changes in gene transcription cascades underlie changes in synaptic, neurotrophic, and inflammatory phenotypic networks during brain Development and Aging. Early postnatal expression changes relate to neuronal, glial, and myelin growth and synaptic pruning events, while late Aging is associated with pro-inflammatory and synaptic loss changes. Thus, comparable transcriptional regulatory networks that operate throughout the lifespan underlie different phenotypic processes during Aging compared to Development.
C1 [Primiani, Christopher T.; Ryan, Veronica H.; Rao, Jagadeesh S.; Modi, Hiren R.; Rapoport, Stanley I.] NIA, Brain Physiol & Metab Sect, Lab Neurosci, NIH, Bethesda, MD 20892 USA.
[Cam, Margaret C.] NCI, Off Sci & Technol Resources, NIH, Bethesda, MD 20892 USA.
[Ahn, Kwangmi] NIMH, Child Psychiat Branch, NIH, Bethesda, MD 20892 USA.
RP Primiani, CT (reprint author), NIA, Brain Physiol & Metab Sect, Lab Neurosci, NIH, Bethesda, MD 20892 USA.
EM christopher.primiani@nih.gov
FU Intramural Research Program of the National Institute on Aging at the
National Institutes of Health
FX The Intramural Research Program of the National Institute on Aging at
the National Institutes of Health supported this research. The funders
had no role in study design, data collection and analysis, decision to
publish, or preparation of the manuscript.
NR 114
TC 9
Z9 9
U1 0
U2 5
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD OCT 20
PY 2014
VL 9
IS 10
AR e110972
DI 10.1371/journal.pone.0110972
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AS0AY
UT WOS:000343942100106
PM 25329999
ER
PT J
AU van Leeuwen, EM
Smouter, FAS
Kam-Thong, T
Karbalai, N
Smith, AV
Harris, TB
Launer, LJ
Sitlani, CM
Li, G
Brody, JA
Bis, JC
White, CC
Jaiswal, A
Oostra, BA
Hofman, A
Rivadeneira, F
Uitterlinden, AG
Boerwinkle, E
Ballantyne, CM
Gudnason, V
Psaty, BM
Cupples, LA
Jarvelin, MR
Ripatti, S
Isaacs, A
Muller-Myhsok, B
Karssen, LC
van Duijn, CM
AF van Leeuwen, Elisabeth M.
Smouter, Francoise A. S.
Kam-Thong, Tony
Karbalai, Nazanin
Smith, Albert V.
Harris, Tamara B.
Launer, Lenore J.
Sitlani, Colleen M.
Li, Guo
Brody, Jennifer A.
Bis, Joshua C.
White, Charles C.
Jaiswal, Alok
Oostra, Ben A.
Hofman, Albert
Rivadeneira, Fernando
Uitterlinden, Andre G.
Boerwinkle, Eric
Ballantyne, Christie M.
Gudnason, Vilmundur
Psaty, Bruce M.
Cupples, L. Adrienne
Jaervelin, Marjo-Riitta
Ripatti, Samuli
Isaacs, Aaron
Mueller-Myhsok, Bertram
Karssen, Lennart C.
van Duijn, Cornelia M.
TI The Challenges of Genome-Wide Interaction Studies: Lessons to Learn from
the Analysis of HDL Blood Levels
SO PLOS ONE
LA English
DT Article
ID CORONARY-HEART-DISEASE; DNA METHYLATION; LOCI; POPULATION; LIPIDS; RISK
AB Genome-wide association studies (GWAS) have revealed 74 single nucleotide polymorphisms (SNPs) associated with high-density lipoprotein cholesterol (HDL) blood levels. This study is, to our knowledge, the first genome-wide interaction study (GWIS) to identify SNPxSNP interactions associated with HDL levels. We performed a GWIS in the Rotterdam Study (RS) cohort I (RS-I) using the GLIDE tool which leverages the massively parallel computing power of Graphics Processing Units (GPUs) to perform linear regression on all genome-wide pairs of SNPs. By performing a meta-analysis together with Rotterdam Study cohorts II and III (RS-II and RS-III), we were able to filter 181 interaction terms with a p-value<1 . 10(-8) that replicated in the two independent cohorts. We were not able to replicate any of these interaction term in the AGES, ARIC, CHS, ERF, FHS and NFBC-66 cohorts (N-total = 30,011) when adjusting for multiple testing. Our GWIS resulted in the consistent finding of a possible interaction between rs774801 in ARMC8 (ENSG00000114098) and rs12442098 in SPATA8 (ENSG00000185594) being associated with HDL levels. However, p-values do not reach the preset Bonferroni correction of the p-values. Our study suggest that even for highly genetically determined traits such as HDL the sample sizes needed to detect SNPxSNP interactions are large and the 2-step filtering approaches do not yield a solution. Here we present our analysis plan and our reservations concerning GWIS.
C1 [van Leeuwen, Elisabeth M.; Smouter, Francoise A. S.; Isaacs, Aaron; Karssen, Lennart C.; van Duijn, Cornelia M.] Erasmus MC, Dept Epidemiol, Genet Epidemiol Unit, Rotterdam, Netherlands.
[Kam-Thong, Tony; Karbalai, Nazanin; Mueller-Myhsok, Bertram] Max Planck Inst Psychiat, D-80804 Munich, Germany.
[Smith, Albert V.; Gudnason, Vilmundur] Iceland & Univ Iceland, Iceland Heart Assoc, Reykjavik, Iceland.
[Harris, Tamara B.; Launer, Lenore J.] Natl Inst Aging, Lab Epidemiol Demog & Biometry, NIH, Bethesda, MD USA.
[Sitlani, Colleen M.; Li, Guo; Brody, Jennifer A.; Bis, Joshua C.] Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA.
[Sitlani, Colleen M.; Li, Guo; Brody, Jennifer A.; Bis, Joshua C.] Univ Washington, Dept Med, Seattle, WA 98195 USA.
[White, Charles C.; Cupples, L. Adrienne] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA.
[Jaiswal, Alok; Ripatti, Samuli] Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki, Finland.
[Oostra, Ben A.] Erasmus MC, Dept Clin Genet, Rotterdam, Netherlands.
[Hofman, Albert; Rivadeneira, Fernando; Uitterlinden, Andre G.] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.
[Hofman, Albert; Rivadeneira, Fernando; Uitterlinden, Andre G.] Erasmus MC, Dept Internal Med, Rotterdam, Netherlands.
[Boerwinkle, Eric] Univ Texas Hlth Sci Ctr Houston, Ctr Human Genet, Sch Publ Hlth, Houston, TX 77030 USA.
[Ballantyne, Christie M.] Baylor Coll Med, Dept Med, Houston, TX 77030 USA.
[Psaty, Bruce M.] Univ Washington, Dept Epidemiol, Seattle, WA USA.
[Psaty, Bruce M.] Univ Washington, Dept Med, Hlth Serv, Seattle, WA USA.
[Psaty, Bruce M.] Grp Hlth Res Inst, Grp Hlth, Seattle, WA USA.
[Cupples, L. Adrienne] Framingham Heart Dis Epidemiol Study, Framingham, MA USA.
[Jaervelin, Marjo-Riitta] Univ London Imperial Coll Sci Technol & Med, MRC Hlth Protect Agcy HPA Ctr Environm & Hlth, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England.
[Jaervelin, Marjo-Riitta] Natl Inst Hlth & Welf, Oulu, Finland.
[Jaervelin, Marjo-Riitta] Univ Oulu, Bioctr Oulu, Oulu, Finland.
[Jaervelin, Marjo-Riitta] Univ Oulu, Inst Hlth Sci, Oulu, Finland.
[Jaervelin, Marjo-Riitta] Oulu Univ Hosp, Unit Primary Care, Oulu, Finland.
[Ripatti, Samuli] Wellcome Trust Sanger Inst, Cambridge, England.
[Ripatti, Samuli] Univ Helsinki, Hjelt Inst, Helsinki, Finland.
[Mueller-Myhsok, Bertram] Munich Cluster Syst Neurol Synergy, Munich, Germany.
[Mueller-Myhsok, Bertram] Univ Liverpool, Inst Translat Med, Liverpool L69 3BX, Merseyside, England.
RP van Duijn, CM (reprint author), Erasmus MC, Dept Epidemiol, Genet Epidemiol Unit, Rotterdam, Netherlands.
EM c.vanduijn@erasmusmc.nl
RI Gudnason, Vilmundur/K-6885-2015; Ripatti, Samuli/H-9446-2014;
Rivadeneira, Fernando/O-5385-2015; Smith, Albert/K-5150-2015
OI Jarvelin, Marjo-Riitta/0000-0002-2149-0630; Karssen, Lennart
C./0000-0002-1959-342X; Gudnason, Vilmundur/0000-0001-5696-0084;
Ripatti, Samuli/0000-0002-0504-1202; Rivadeneira,
Fernando/0000-0001-9435-9441; Smith, Albert/0000-0003-1942-5845
FU CHANCES project [242244]; BBMRI-NL, a Research Infrastructure - Dutch
government [NWO 184.021.007]; Erasmus Medical Center; Erasmus
University, Rotterdam; Netherlands Organization for the Health Research
and Development (ZonMw); Research Institute for Diseases in the Elderly
(RIDE); Ministry of Education, Culture and Science; Ministry for Health,
Welfare and Sports; European Commission (DG XII); Municipality of
Rotterdam; Research Institute for Diseases in the Elderly [014-93-015,
RIDE2]; Netherlands Genomics Initiative (NGI)/Netherlands Organisation
for Scientific Research (NWO) project [050-060-810]; European Commission
FP6 STRP grant [018947 (LSHG-CT-2006-01947)]; European Community by the
European Commission [HEALTH-F4-2007-201413, similar
toQLG2-CT-2002-01254]; ENGAGE consortium; CMSB; Netherlands Organisation
for Scientific Research; Russian Foundation for Basic Research [NWO-RFBR
047.017.043]; NHLBI [HHSN268201200036C, HHSN268200800007C, N01HC55222,
N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086,
HL080295, HL087652, HL105756]; National Institute of Neurological
Disorders and Stroke (NINDS); National Institute on Aging (NIA)
[AG023629]; National Center for Research Resources [UL1RR033176];
National Center for Advancing Translational Sciences, CTSI grant
[UL1TR000124]; National Institute of Diabetes and Digestive and Kidney
Disease grant [DK063491]; Southern California Diabetes Endocrinology
Research Center; Academy of Finland [251217]; Finnish foundation for
Cardiovascular Research; Sigrid Juselius Foundation; NIH
FX This project was supported by the CHANCES project funded in the FP7
framework programme of DG-RESEARCH in the European Commission (grant no.
242244) and by BBMRI-NL, a Research Infrastructure financed by the Dutch
government (NWO 184.021.007). The Rotterdam Study is funded by Erasmus
Medical Center and Erasmus University, Rotterdam, Netherlands
Organization for the Health Research and Development (ZonMw), the
Research Institute for Diseases in the Elderly (RIDE), the Ministry of
Education, Culture and Science, the Ministry for Health, Welfare and
Sports, the European Commission (DG XII), and the Municipality of
Rotterdam. 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 ERF study as a part of EuroSPAN (European Special
Populations Research Network) was supported by European Commission FP6
STRP grant number 018947 (LSHG-CT-2006-01947) and also received funding
from the European Community's Seventh Framework Programme
(FP7/2007-2013)/grant agreement HEALTH-F4-2007-201413 by the European
Commission under the programme "Quality of Life and Management of the
Living Resources'' of 5th Framework Programme (no.similar to
QLG2-CT-2002-01254). The ERF study was further supported by ENGAGE
consortium and CMSB. High-throughput analysis of the ERF data was
supported by a joint grant from the Netherlands Organisation for
Scientific Research and the Russian Foundation for Basic Research
(NWO-RFBR 047.017.043). This CHS research was supported by NHLBI
contracts HHSN268201200036C, HHSN268200800007C, N01HC55222, N01HC85079,
N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086; and NHLBI
grants HL080295, HL087652, HL105756, with additional contribution from
the National Institute of Neurological Disorders and Stroke (NINDS).
Additional support was provided through AG023629 from the National
Institute on Aging (NIA). DNA handling and genotyping at Cedars-Sinai
Medical Center was supported in part by the National Center for Research
Resources, grant UL1RR033176, and is now at the National Center for
Advancing Translational Sciences, CTSI grant UL1TR000124, in addition to
the National Institute of Diabetes and Digestive and Kidney Disease
grant DK063491 to the Southern California Diabetes Endocrinology
Research Center. Samuli Ripatti was supported by Academy of Finland
(251217), the Finnish foundation for Cardiovascular Research and the
Sigrid Juselius Foundation. Christie M. Ballantyne was funded by the
NIH. None of the funders had a role in study design, data analysis,
decision to publish, or preparation of the manuscript.
NR 22
TC 3
Z9 3
U1 1
U2 5
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD OCT 20
PY 2014
VL 9
IS 10
AR e109290
DI 10.1371/journal.pone.0109290
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AS0AY
UT WOS:000343942100019
PM 25329471
ER
PT J
AU Danielsen, R
Aspelund, T
Harris, TB
Gudnason, V
AF Danielsen, Ragnar
Aspelund, Thor
Harris, Tamara B.
Gudnason, Vilmundur
TI The prevalence of aortic stenosis in the elderly in Iceland and
predictions for the coming decades: The AGES-Reykjavik study
SO INTERNATIONAL JOURNAL OF CARDIOLOGY
LA English
DT Article
DE Aortic valve stenosis; Epidemiology; Prevalence; Elderly; Future
prediction
ID VALVE CALCIFICATION; CLINICAL-OUTCOMES; EJECTION FRACTION; DISEASE;
SEVERITY; IMPLANTATION; PROGRESSION; ECHOCARDIOGRAPHY; FEATURES; SURGERY
AB Aims: To evaluate the prevalence of significant aortic valve stenosis (AS) in a randomly selected study population of elderly individuals representing the general population of Iceland. Furthermore, to predict the number of individuals likely to have severe AS in the future.
Methods and results: Echocardiography and computed tomography (CT) data from individuals who participated in the AGES-Reykjavik study were used. Echocardiography data from 685 individuals (58% females) aged 6795 years were available. In both sexes combined, the prevalence for severe AS, defined as an aortic valve area index of <0.6 cm(2)/m(2), in the age groups <70, 70-79 and >= 80 years was 0.92%, 2.4% and 7.3%, respectively. A ROC analysis on the relation between the echocardiography data and the aortic valve calcium score on CT defined a score >= 500 to be indicative of severe AS. Subsequently, in a CT study cohort of 5256 individuals the prevalence of severe AS in the same age groups was 0.80%, 4.0% and 9.5%, respectively. Overall, the prevalence of severe AS by echocardiography and CT in individuals >= 70 years was 4.3% and 5.9%, respectively. A prediction on the number of elderly >= 70 years for the coming decades demonstrated that patients with severe AS will have increased 2.4 fold by the year 2040 and will more than triple by the year 2060.
Conclusion: This study, in a cohort of elderly individuals representative of the general population in a Nordic country, predicts that AS will be a large health problem in the coming decades. (C) 2014 Elsevier Ireland Ltd. All rights reserved.
C1 [Danielsen, Ragnar] Univ Hosp, Landspitali, Dept Cardiol, Reykjavik, Iceland.
[Aspelund, Thor; Gudnason, Vilmundur] Icelandic Heart Assoc Res Inst, Kopavogur, Iceland.
[Aspelund, Thor; Gudnason, Vilmundur] Univ Iceland, Reykjavik, Iceland.
[Harris, Tamara B.] NIA, Lab Epidemiol & Populat Sci, Bethesda, MD 20892 USA.
RP Danielsen, R (reprint author), Univ Hosp, Landspitali, Dept Cardiol, Reykjavik, Iceland.
EM ragnarda@landspitali.is
RI Gudnason, Vilmundur/K-6885-2015
OI Gudnason, Vilmundur/0000-0001-5696-0084
FU NIH [N01-AG-1-2100]; NIA Intramural Research Program, Hjartavernd (the
Icelandic Heart Association); Althingi (the Icelandic Parliament)
FX The AGES-Reykjavik study was funded by NIH contract N01-AG-1-2100, the
NIA Intramural Research Program, Hjartavernd (the Icelandic Heart
Association), and the Althingi (the Icelandic Parliament).
NR 32
TC 7
Z9 7
U1 0
U2 1
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 OCT 20
PY 2014
VL 176
IS 3
BP 916
EP 922
DI 10.1016/j.ijcard.2014.08.053
PG 7
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA AR9KT
UT WOS:000343893300078
PM 25171970
ER
PT J
AU Teruya, C
Schwartz, RP
Mitchell, SG
Hasson, AL
Thomas, C
Buoncristiani, SH
Hser, YI
Wiest, K
Cohen, AJ
Glick, N
Jacobs, P
McLaughlin, P
Ling, W
AF Teruya, Cheryl
Schwartz, Robert P.
Mitchell, Shannon Gwin
Hasson, Albert L.
Thomas, Christie
Buoncristiani, Samantha H.
Hser, Yih-Ing
Wiest, Katharina
Cohen, Allan J.
Glick, Naomi
Jacobs, Petra
McLaughlin, Paul
Ling, Walter
TI Patient Perspectives on Buprenorphine/Naloxone: A Qualitative Study of
Retention During the Starting Treatment with Agonist Replacement
Therapies (START) Study
SO JOURNAL OF PSYCHOACTIVE DRUGS
LA English
DT Article
DE retention; qualitative; patient perspectives; buprenorphine
ID METHADONE-MAINTENANCE TREATMENT; DRUG-ABUSE TREATMENT; FOLLOW-UP
OUTCOMES; OPIOID-DEPENDENT PATIENTS; DOUBLE-BLIND TRIAL;
OUT-OF-TREATMENT; HEROIN USERS; RISK; PREDICTORS; ADDICTION
AB This study examines the barriers and facilitators of retention among patients receiving buprenorphine/naloxone at eight community-based opioid treatment programs across the United States. Participants (n = 105) were recruited up to three and a half years after having participated in a randomized clinical trial comparing the effect of buprenorphine/naloxone and methadone on liver function. Semi-structured interviews were conducted with 67 patients provided with buprenorphine/naloxone who had terminated early and 38 patients who had completed at least 24 weeks of the trial. Qualitative data were analyzed using the constant comparison method. Barriers to buprenorphine/naloxone retention that emerged included factors associated with: (1) the design of the clinical trial; (2) negative medication or treatment experience; and (3) personal circumstances. The facilitators comprised: (1) positive experience with the medication; (2) personal determination and commitment to complete; and (3) staff encouragement and support. The themes drawn from interviews highlight the importance of considering patients' prior experience with buprenorphine/naloxone and methadone, medication preference, personal circumstances, and motivation to abstain from illicit use or misuse of opioids, as these may influence retention. Ongoing education of patients and staff regarding buprenorphine/naloxone, especially in comparison to methadone, and support from staff and peers are essential.
C1 [Teruya, Cheryl; Hasson, Albert L.; Thomas, Christie; Hser, Yih-Ing; Glick, Naomi; Ling, Walter] Univ Calif Los Angeles, Integrated Subst Abuse Programs, Los Angeles, CA 90025 USA.
[Schwartz, Robert P.] Friends Res Inst, Baltimore, MD USA.
[Mitchell, Shannon Gwin; Buoncristiani, Samantha H.] Friends Med Res Inst Inc, Baltimore, MD USA.
[Wiest, Katharina] CODA Inc, Res, Portland, OR USA.
[Cohen, Allan J.] Bay Area Addict Res & Treatment, San Francisco, CA USA.
[Jacobs, Petra] NIDA, Ctr Clin Trials Network, Bethesda, MD 20892 USA.
[McLaughlin, Paul] Hartford Dispensary, Manchester, CT USA.
RP Teruya, C (reprint author), Univ Calif Los Angeles, Integrated Subst Abuse Programs, 11075 Santa Monica Blvd,Ste 100, Los Angeles, CA 90025 USA.
EM cteruya@ucla.edu
FU NIDA NIH HHS [K05 DA017648, P30 DA016383, U10 DA013045, U10DA13045]
NR 71
TC 7
Z9 7
U1 9
U2 20
PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD
PI ABINGDON
PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND
SN 0279-1072
EI 2159-9777
J9 J PSYCHOACTIVE DRUGS
JI J. Psychoact. Drugs
PD OCT 20
PY 2014
VL 46
IS 5
BP 412
EP 426
DI 10.1080/02791072.2014.921743
PG 15
WC Psychology, Clinical; Substance Abuse
SC Psychology; Substance Abuse
GA AS0SE
UT WOS:000343987500010
PM 25364994
ER
PT J
AU Siendones, E
SantaCruz-Calvo, S
Martin-Montalvo, A
Cascajo, MV
Ariza, J
Lopez-Lluch, G
Villalba, JM
Acquaviva-Bourdain, C
Roze, E
Bernier, M
de Cabo, R
Navas, P
AF Siendones, Emilio
SantaCruz-Calvo, Sara
Martin-Montalvo, Alejandro
Cascajo, Maria V.
Ariza, Julia
Lopez-Lluch, Guillermo
Villalba, Jose M.
Acquaviva-Bourdain, Cecile
Roze, Emmanuel
Bernier, Michel
de Cabo, Rafael
Navas, Placido
TI Membrane-Bound CYB5R3 Is a Common Effector of Nutritional and Oxidative
Stress Response Through FOXO3a and Nrf2
SO ANTIOXIDANTS & REDOX SIGNALING
LA English
DT Article
ID CYTOCHROME B(5) REDUCTASE; TRANSCRIPTION FACTOR FOXO3A; PLASMA-MEMBRANE;
COENZYME-Q; RAT-LIVER; CALORIC RESTRICTION; COQ(10) DEFICIENCY; NAD(+)
DEPLETION; PROTECTS NEURONS; LIFE-SPAN
AB Aims: Membrane-bound CYB5R3 deficiency in humans causes recessive hereditary methaemoglobinaemia (RHM), an incurable disease that is characterized by severe neurological disorders. CYB5R3 encodes for NADH-dependent redox enzyme that contributes to metabolic homeostasis and stress protection; however, how it is involved in the neurological pathology of RHM remains unknown. Here, the role and transcriptional regulation of CYB5R3 was studied under nutritional and oxidative stress. Results: CYB5R3-deficient cells exhibited a decrease of the NAD(+)/NADH ratio, mitochondrial respiration rate, ATP production, and mitochondrial electron transport chain activities, which were associated with higher sensitivity to oxidative stress, and an increase in senescence-associated beta-galactosidase activity. Overexpression of either forkhead box class O 3a (FOXO3a) or nuclear factor (erythroid-derived 2)-like2 (Nrf2) was associated with increased CYB5R3 levels, and genetic ablation of Nrf2 resulted in lower CYB5R3 expression. The presence of two antioxidant response element sequences in the CYB5R3 promoter led to chromatin immunoprecipitation studies, which showed that cellular stressors enhanced the binding of Nrf2 and FOXO3a to the CYB5R3 promoter. Innovation: Our findings demonstrate that CYB5R3 contributes to regulate redox homeostasis, aerobic metabolism, and cellular senescence, suggesting that CYB5R3 might be a key effector of oxidative and nutritional stress pathways. The expression of CYB5R3 is regulated by the cooperation of Nrf2 and FOXO3a. Conclusion: CYB5R3 is an essential gene that appears as a final effector for both nutritional and oxidative stress responses through FOXO3a and Nrf2, respectively, and their interaction promotes CYB5R3 expression. These results unveil a potential mechanism of action by which CYB5R3 deficiency contributes to the pathophysiological underpinnings of neurological disorders in RHM patients. Antioxid. Redox Signal. 21, 1708-1725.
C1 [Siendones, Emilio; SantaCruz-Calvo, Sara; Cascajo, Maria V.; Lopez-Lluch, Guillermo; Navas, Placido] Univ Pablo de Olavide, Ctr Andaluz Biol Desarrollo, CSIC JA, Seville 41013, Spain.
[Siendones, Emilio; SantaCruz-Calvo, Sara; Cascajo, Maria V.; Lopez-Lluch, Guillermo; Navas, Placido] ISCIII, Ctr Biomed Res Rare Dis CIBERER, E-41013 Seville, Spain.
[Martin-Montalvo, Alejandro; Bernier, Michel; de Cabo, Rafael] NIA, Translat Gerontol Branch, NIH, Baltimore, MD 21224 USA.
[Ariza, Julia; Villalba, Jose M.] Univ Cordoba, Dept Biol Celular Fisiol & Immunol, Cordoba, Spain.
[Acquaviva-Bourdain, Cecile] Ctr Biol & Pathol, Serv Malad Hereditaires Metab & Depistage Neonata, Lyon, France.
[Roze, Emmanuel] Univ Paris 06, Ctr Rech Inst Cerveau & Moelle Epiniere CRICM, INSERM, U975,CNRS,UMR 7225,UMR S 975, Paris, France.
RP Navas, P (reprint author), Univ Pablo de Olavide, Ctr Andaluz Biol Desarrollo, Carretera Utrera Km 1, Seville 41013, Spain.
EM pnavas@upo.es
RI Lopez-Lluch, Guillermo/N-4742-2014; de Cabo, Rafael/J-5230-2016;
Martin-Montalvo, Alejandro/C-2031-2017;
OI Lopez-Lluch, Guillermo/0000-0001-9830-8502; de Cabo,
Rafael/0000-0002-3354-2442; Martin-Montalvo,
Alejandro/0000-0002-3886-5355; Bernier, Michel/0000-0002-5948-368X; ,
rafael/0000-0003-2830-5693
FU Spanish FIS grant [PI11/00078]; Junta de Andalucia grant [P08-CTS-03988]
FX This work has been partially funded by the Spanish FIS grant
(PI11/00078) and Junta de Andalucia grant P08-CTS-03988. The authors
would like to thank Jose Manuel Cuezva and Maria Sanchez-Arago for
helping them with the XF24 Extracellular Flux Analyzer and the
interpretation of mitochondrial consumption rate results.
NR 66
TC 4
Z9 4
U1 0
U2 12
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1523-0864
EI 1557-7716
J9 ANTIOXID REDOX SIGN
JI Antioxid. Redox Signal.
PD OCT 20
PY 2014
VL 21
IS 12
BP 1708
EP 1725
DI 10.1089/ars.2013.5479
PG 18
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA AQ1SH
UT WOS:000342560800003
PM 24450884
ER
PT J
AU Baskaran, K
Duarte, JM
Biyani, N
Bliven, S
Capitani, G
AF Baskaran, Kumaran
Duarte, Jose M.
Biyani, Nikhil
Bliven, Spencer
Capitani, Guido
TI A PDB-wide, evolution-based assessment of protein-protein interfaces
SO BMC STRUCTURAL BIOLOGY
LA English
DT Article
DE Protein-protein interfaces; Biological interfaces; Crystal contacts;
EPPIC; PISA; PDB
ID QUATERNARY STRUCTURE; HOMOLOGOUS PROTEINS; CRYSTALS; OLIGOMERIZATION;
DATABASE
AB Background: Thanks to the growth in sequence and structure databases, more than 50 million sequences are now available in UniProt and 100,000 structures in the PDB. Rich information about protein-protein interfaces can be obtained by a comprehensive study of protein contacts in the PDB, their sequence conservation and geometric features.
Results: An automated computational pipeline was developed to run our Evolutionary Protein-Protein Interface Classifier (EPPIC) software on the entire PDB and store the results in a relational database, currently containing > 800,000 interfaces. This allows the analysis of interface data on a PDB-wide scale. Two large benchmark datasets of biological interfaces and crystal contacts, each containing about 3000 entries, were automatically generated based on criteria thought to be strong indicators of interface type. The BioMany set of biological interfaces includes NMR dimers solved as crystal structures and interfaces that are preserved across diverse crystal forms, as catalogued by the Protein Common Interface Database (ProtCID) from Xu and Dunbrack. The second dataset, XtalMany, is derived from interfaces that would lead to infinite assemblies and are therefore crystal contacts. BioMany and XtalMany were used to benchmark the EPPIC approach. The performance of EPPIC was also compared to classifications from the Protein Interfaces, Surfaces, and Assemblies (PISA) program on a PDB-wide scale, finding that the two approaches give the same call in about 88% of PDB interfaces. By comparing our safest predictions to the PDB author annotations, we provide a lower-bound estimate of the error rate of biological unit annotations in the PDB. Additionally, we developed a PyMOL plugin for direct download and easy visualization of EPPIC interfaces for any PDB entry. Both the datasets and the PyMOL plugin are available at http://www.eppic-web.org/ewui/#downloads.
Conclusions: Our computational pipeline allows us to analyze protein-protein contacts and their sequence conservation across the entire PDB. Two new benchmark datasets are provided, which are over an order of magnitude larger than existing manually curated ones. These tools enable the comprehensive study of several aspects of protein-protein contacts in the PDB and represent a basis for future, even larger scale studies of protein-protein interactions.
C1 [Baskaran, Kumaran; Duarte, Jose M.; Biyani, Nikhil; Bliven, Spencer; Capitani, Guido] Paul Scherrer Inst, Lab Biomol Res, CH-5232 Villigen, Switzerland.
[Duarte, Jose M.] ETH, Inst Mol Biol & Biophys, CH-8093 Zurich, Switzerland.
[Bliven, Spencer] Univ Calif San Diego, Bioinformat & Syst Biol Program, La Jolla, CA 92093 USA.
[Bliven, Spencer] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
RP Capitani, G (reprint author), Paul Scherrer Inst, Lab Biomol Res, OFLC 110, CH-5232 Villigen, Switzerland.
EM guido.capitani@psi.ch
OI Bliven, Spencer/0000-0002-1200-1698; Biyani, Nikhil/0000-0002-5405-7112
FU Research Committee of the Paul Scherrer Institute; Swiss National
Science Foundation [FK-05.08.1, FK-04.09.1, 140879]; Intramural Research
Program of the National Center for Biotechnology Information, National
Library of Medicine, National Institutes of Health
FX Financial support from the Research Committee of the Paul Scherrer
Institute and the Swiss National Science Foundation to GC (grant numbers
FK-05.08.1, FK-04.09.1 and 140879, respectively) is gratefully
acknowledged. SB was supported by the Intramural Research Program of the
National Center for Biotechnology Information, National Library of
Medicine, National Institutes of Health.
NR 22
TC 6
Z9 6
U1 2
U2 7
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1472-6807
J9 BMC STRUCT BIOL
JI BMC Struct. Biol.
PD OCT 18
PY 2014
VL 14
AR 22
DI 10.1186/s12900-014-0022-0
PG 11
WC Biophysics
SC Biophysics
GA AT4FZ
UT WOS:000344896500001
PM 25326082
ER
PT J
AU Kohli, A
Murphy, AA
Agarwal, C
Shivakumar, B
Kottilil, S
Polis, MA
Subramanian, GM
Midha, V
Goyal, O
Desai, S
Sood, A
Shah, S
AF Kohli, Anita
Murphy, Allison A.
Agarwal, Chirdeep
Shivakumar, Bhavana
Kottilil, Shyam
Polis, Michael A.
Subramanian, G. Mani
Midha, Vandana
Goyal, Omesh
Desai, Srinivas
Sood, Ajit
Shah, Samir
TI HCC surveillance results in earlier HCC detection: results from an
Indian cohort
SO SPRINGERPLUS
LA English
DT Article
DE Hepatocellular carcinoma; Surveillance; Ultrasounds; Survival;
Treatment; India
ID HEPATOCELLULAR-CARCINOMA; ALPHA-FETOPROTEIN; HEPATITIS; EPIDEMIOLOGY;
CIRRHOSIS; STRATEGY
AB Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related death worldwide, with an increased incidence in South Asia. In order to describe the effect of surveillance for HCC with biannual ultrasound and alpha-fetoprotein (AFP) on diagnosis and survival in an Indian population a retrospective cohort-control study was performed at two liver clinics in India. The medical records of 3,258 patients with cirrhosis who received surveillance for HCC were reviewed, and 100 patients who developed HCC identified. Sixty-four cirrhotic patients diagnosed with HCC during the same time period without a history of surveillance were included and survival, BCLC stage at diagnosis, and treatment were compared.
Patients who underwent surveillance were more likely to be diagnosed with potentially curable or treatable BCLC Stage 0/A disease and Stage B/C disease respectively, than late Stage D disease (chi(2) = 0.0007). Patients diagnosed at an earlier stage of HCC lived significantly longer after diagnosis than patients diagnosed at a later stage (Stage 0/A: 15.6 +/- 14.2 months vs. Stage B/C: 9.43 +/- 19.7 months vs. Stage D: 5.59 +/- 11.9 months; p = 0.0006). While treatment for HCC improved overall survival, only 28% of eligible patients received treatment, explaining the lack of survival benefit noted in the surveillance group. Surveillance for HCC led to detection of HCC at earlier stages. The impact of surveillance on improved mortality could not be evaluated given the limited number of patients who received treatment. HCC surveillance has the potential to improve survival in South Asian patients with cirrhosis only if improvements in access to appropriate treatment are made.
C1 [Kohli, Anita; Murphy, Allison A.; Shivakumar, Bhavana; Kottilil, Shyam; Polis, Michael A.] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA.
[Agarwal, Chirdeep; Shah, Samir] Jaslok Hosp, Dept Gastroenterol, Mumbai, Maharashtra, India.
[Midha, Vandana; Goyal, Omesh; Sood, Ajit] Dayanand Med Coll & Hosp, Ludhiana, Punjab, India.
[Desai, Srinivas] Jaslok Hosp, Dept Radiol, Mumbai, Maharashtra, India.
[Kohli, Anita] Frederick Natl Lab Canc Res, Leidos Biomed Res Inc, Clin Res Directorate, Clin Monitoring Res Program, Frederick, MD 21702 USA.
[Subramanian, G. Mani] Gilead Sci Inc, Foster City, CA 94404 USA.
RP Shah, S (reprint author), Jaslok Hosp, Dept Gastroenterol, Mumbai, Maharashtra, India.
EM drshahsamir@gmail.com
FU National Cancer Institute, National Institutes of Health
[HHSN261200800001E]; National Institute of Allergy and Infectious
Diseases
FX This project has been funded in whole or in part with federal funds from
the National Cancer Institute, National Institutes of Health, under
Contract No. HHSN261200800001E. 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 Diseases.
NR 15
TC 1
Z9 1
U1 0
U2 0
PU SPRINGER INTERNATIONAL PUBLISHING AG
PI CHAM
PA GEWERBESTRASSE 11, CHAM, CH-6330, SWITZERLAND
SN 2193-1801
J9 SPRINGERPLUS
JI SpringerPlus
PD OCT 17
PY 2014
VL 3
AR 610
DI 10.1186/2193-1801-3-610
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CO4DM
UT WOS:000359110700004
PM 25392781
ER
PT J
AU Stichelen, SOV
Abramowitz, LK
Hanover, JA
AF Stichelen, Stephanie Olivier-Van
Abramowitz, Lara K.
Hanover, John A.
TI X marks the spot: Does it matter that O-GlcNAc Transferase is an
X-linked gene?
SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
LA English
DT Review
DE O-GlcNAc Transferase; O-GIcNAcylation; X-linked gene; X-inactivation;
Embryogenesis
ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; PREIMPLANTATION MOUSE EMBRYOS; HISTONE
VARIANT MACROH2A; CHROMOSOME INACTIVATION; XIST RNA; DNA METHYLATION;
KLINEFELTERS-SYNDROME; INSULIN-RESISTANCE; BREAST-CANCER; STEM-CELLS
AB O-GlcNAcylation has emerged as a critical post-translational modification important for a wide array of cellular processes. This modification has been identified on a large pool of intracellular proteins that have wide-ranging roles, including transcriptional regulation, cell cycle progression, and signaling, among others. Interestingly, in mammals the single gene encoding O-GlcNAc Transferase (OGT) is located on the X-chromosome near the Xist locus suggesting that tight dosage regulation is necessary for normal development. Herein, we highlight the importance of OGT dosage and consider how its genomic location can contribute to a gender-specific increased risk for a number of diseases. Published by Elsevier Inc.
C1 [Stichelen, Stephanie Olivier-Van; Abramowitz, Lara K.; Hanover, John A.] NIDDK, Lab Cellular & Mol Biol, NIH, Bethesda, MD 20892 USA.
RP Hanover, JA (reprint author), 9000 Rockville Pike,Bd8,Room B127, Bethesda, MD 20892 USA.
EM jah@helix.nih.gov
NR 88
TC 0
Z9 0
U1 1
U2 9
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0006-291X
EI 1090-2104
J9 BIOCHEM BIOPH RES CO
JI Biochem. Biophys. Res. Commun.
PD OCT 17
PY 2014
VL 453
IS 2
BP 201
EP 207
DI 10.1016/j.bbrc.2014.06.068
PG 7
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA AU9CO
UT WOS:000345889500002
ER
PT J
AU Lobkovsky, AE
Wolf, YI
Koonin, EV
AF Lobkovsky, Alexander E.
Wolf, Yuri I.
Koonin, Eugene V.
TI Estimation of prokaryotic supergenome size and composition from gene
frequency distributions
SO BMC GENOMICS
LA English
DT Article; Proceedings Paper
CT 12th Annual Research in Computational Molecular Biology (RECOMB)
Satellite Workshop on Comparative Genomics
CY OCT 19-22, 2014
CL Cold Spring Harbor Lab, Cold Spring Harbor, NY
HO Cold Spring Harbor Lab
ID BACTERIAL PAN-GENOME; EVOLUTION; MODEL; SUPRAGENOME; ARCHAEAL
AB Background: Because prokaryotic genomes experience a rapid flux of genes, selection may act at a higher level than an individual genome. We explore a quantitative model of the distributed genome whereby groups of genomes evolve by acquiring genes from a fixed reservoir which we denote as supergenome. Previous attempts to understand the nature of the supergenome treated genomes as random, independent collections of genes and assumed that the supergenome consists of a small number of homogeneous sub-reservoirs. Here we explore the consequences of relaxing both assumptions.
Results: We surveyed several methods for estimating the size and composition of the supergenome. The methods assumed that genomes were either random, independent samples of the supergenome or that they evolved from a common ancestor along a known tree via stochastic sampling from the reservoir. The reservoir was assumed to be either a collection of homogeneous sub-reservoirs or alternatively composed of genes with Gamma distributed gain probabilities. Empirical gene frequencies were used to either compute the likelihood of the data directly or first to reconstruct the history of gene gains and then compute the likelihood of the reconstructed numbers of gains.
Conclusions: Supergenome size estimates using the empirical gene frequencies directly are not robust with respect to the choice of the model. By contrast, using the gene frequencies and the phylogenetic tree to reconstruct multiple gene gains produces reliable estimates of the supergenome size and indicates that a homogeneous supergenome is more consistent with the data than a supergenome with Gamma distributed gain probabilities.
C1 [Lobkovsky, Alexander E.; Wolf, Yuri I.; Koonin, Eugene V.] NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20892 USA.
RP Koonin, EV (reprint author), NIH, Natl Ctr Biotechnol Informat, 8600 Rockville Pike, Bethesda, MD 20892 USA.
EM koonin@ncbi.nlm.nih.gov
FU Intramural NIH HHS
NR 28
TC 5
Z9 5
U1 0
U2 0
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2164
J9 BMC GENOMICS
JI BMC Genomics
PD OCT 17
PY 2014
VL 15
SU 6
AR S14
DI 10.1186/1471-2164-15-S6-S14
PG 10
WC Biotechnology & Applied Microbiology; Genetics & Heredity
SC Biotechnology & Applied Microbiology; Genetics & Heredity
GA AU5ZY
UT WOS:000345683000015
PM 25572821
ER
PT J
AU Vigetti, D
Deleonibus, S
Moretto, P
Bowen, T
Fischer, JW
Grandoch, M
Oberhuber, A
Love, DC
Hanover, JA
Cinquetti, R
Karousou, E
Viola, M
D'Angelo, ML
Hascall, VC
De Luca, G
Passi, A
AF Vigetti, Davide
Deleonibus, Sara
Moretto, Paola
Bowen, Timothy
Fischer, Jens W.
Grandoch, Maria
Oberhuber, Alexander
Love, Dona C.
Hanover, John A.
Cinquetti, Raffaella
Karousou, Eugenia
Viola, Manuela
D'Angelo, Maria Luisa
Hascall, Vincent C.
De Luca, Giancarlo
Passi, Alberto
TI Natural Antisense Transcript for Hyaluronan Synthase 2 (HAS2-AS1)
Induces Transcription of HAS2 via Protein O-GlcNAcylation
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID LONG NONCODING RNAS; BETA-N-ACETYLGLUCOSAMINE; SMOOTH-MUSCLE-CELLS;
KAPPA-B ACTIVATION; INSULIN-RESISTANCE; EPIGENETIC REGULATION; HISTONE
MODIFICATIONS; CHROMATIN; GLCNAC; ATHEROSCLEROSIS
AB Changes in the microenvironment organization within vascular walls are critical events in the pathogenesis of vascular pathologies, including atherosclerosis and restenosis. Hyaluronan (HA) accumulation into artery walls supports vessel thickening and is involved in many cardiocirculatory diseases. Excessive cytosolic glucose can enter the hexosamine biosynthetic pathway, increase UDP-N-acetylglucosamine (UDP-GlcNAc) availability, and lead to modification of cytosolic proteins via O-linked attachment of the monosaccharide beta-N-GlcNAc (O-GlcNAcylation) from UDP-GlcNAc by the enzyme O-GlcNAc transferase. As many cytoplasmic and nuclear proteins can be glycosylated by O-GlcNAc, we studied whether the expression of the HA synthases that synthesize HA could be controlled by O-GlcNAcylation in human aortic smooth muscle cells. Among the three HAS isoenzymes, only HAS2 mRNA increased after O-GlcNAcylation induced by glucosamine treatments or by inhibiting O-GlcNAc transferase with PUGNAC (O-(2-acetamido- 2-deoxy-D-glucopyranosylidene) amino-N-phenylcarbamate). We found that the natural antisense transcript of HAS2 (HAS2-AS1) was absolutely necessary to induce the transcription of the HAS2 gene. Moreover, we found that O-GlcNAcylation modulated HAS2-AS1 promoter activation by recruiting the NF-kappa B subunit p65, but not the HAS2 promoter, whereas HAS2-AS1 natural antisense transcript, working in cis, regulated HAS2 transcription by altering the chromatin structure around the HAS2 proximal promoter via O-GlcNAcylation and acetylation. These results indicate that HAS2 transcription can be finely regulated not only by recruiting transcription factors to the promoter as previously described but also by modulating chromatin accessibility by epigenetic modifications.
C1 [Vigetti, Davide; Deleonibus, Sara; Moretto, Paola; Karousou, Eugenia; Viola, Manuela; D'Angelo, Maria Luisa; De Luca, Giancarlo; Passi, Alberto] Univ Insubria, Dipartimento Sci Chirurg & Morfol, I-21100 Varese, Italy.
[Bowen, Timothy] Cardiff Univ, Sch Med, Dept Nephrol, Cardiff CF14 4XN, S Glam, Wales.
[Fischer, Jens W.; Grandoch, Maria] Univ Dusseldorf, Inst Pharmacol & Clin Pharmacol, Univ Hosp Dusseldorf, D-40225 Dusseldorf, Germany.
[Oberhuber, Alexander] Univ Dusseldorf, Univ Hosp Dusseldorf, Dept Vasc & Endovasc Surg, Dusseldorf, Germany.
[Love, Dona C.; Hanover, John A.] NIDDK, Lab Cell Biochem & Biol, NIH, Bethesda, MD 20892 USA.
[Cinquetti, Raffaella] Univ Insubria, Dipertimento Biotecnol & Sci Vita, I-21100 Varese, Italy.
[Hascall, Vincent C.] Cleveland Clin, Biomed Engn ND20, Cleveland, OH 44195 USA.
RP Passi, A (reprint author), Univ Insubria, Dipartimento Sci Chirurg & Morfol, Via JH Dunant 5, I-21100 Varese, Italy.
EM alberto.passi@uninsubria.it
RI Viola, Manuela/B-7120-2011;
OI Viola, Manuela/0000-0002-0634-6390; vigetti, davide/0000-0002-6339-8453;
passi, alberto/0000-0003-3328-3089
FU FAR; PRIN; Fondazione Comunitaria del Vare-sotto-ONLUS; European Union
Grant IRSES INFLAMA; Ph.D. School in Biological and Medical Sciences
FX This work was supported by FAR, PRIN, Fondazione Comunitaria del
Vare-sotto-ONLUS, and European Union Grant IRSES INFLAMA (to A. P.).;
Recipient of a fellowship from the Ph.D. School in Biological and
Medical Sciences.
NR 54
TC 24
Z9 24
U1 2
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 OCT 17
PY 2014
VL 289
IS 42
BP 28816
EP 28826
DI 10.1074/jbc.M114.597401
PG 11
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA AS2XZ
UT WOS:000344141000006
PM 25183006
ER
PT J
AU Gao, Y
Zhao, Y
Pan, JZ
Yang, L
Huang, TT
Feng, XM
Li, C
Liang, SJ
Zhou, DF
Liu, C
Tu, FX
Tao, C
Chen, X
AF Gao, Yong
Zhao, Yun
Pan, Jingzi
Yang, Liu
Huang, Tingting
Feng, Xiaomin
Li, Chao
Liang, Shujing
Zhou, Dingfu
Liu, Chan
Tu, Fengxia
Tao, Cai
Chen, Xiang
TI Treadmill exercise promotes angiogenesis in the ischemic penumbra of rat
brains through caveolin-1/VEGF signaling pathways
SO BRAIN RESEARCH
LA English
DT Article
DE Treadmill; MCAO; Caveolin-1; Angiogenesis; Daidzein
ID ENDOTHELIAL GROWTH-FACTOR; CEREBRAL-ARTERY OCCLUSION; STROKE; INJURY;
ANGIOPOIETINS; EXPRESSION; RECOVERY; CAVEOLAE; BURDEN; VEGF
AB The purpose of this study was to investigate the role of caveolin-1 in treadmill-exercise-induced angiogenesis in the ischemic penumbra of rat brains, and whether caveolin-1 changes correlated with reduced brain injury induced by treadmill exercise, in rats after cerebral ischemia. Rats were randomized into five groups: sham-operated (S, n=7), model (M, n=36), exercise and model (EM, n=36), inhibitor and model (IM, n=36), and inhibitor, exercise, and model (IEM, n=36). Rats in the model groups underwent middle cerebral artery occlusion (MCAO). Rats in the inhibitor groups received an IP injection of the caveolin-1 inhibitor, daidzein (0.4 mg/kg), every 24 h following reperfusion. Rats were killed at 7 or 28 days after the operation. The exercise group showed better neurological recovery and smaller infarction volumes compared with the non-exercise group. Correspondingly, significant increases of caveolin-1 and vascular endothelial growth factor (VEGF) protein expression were observed compared with the non-exercise group. Additionally, the number of Flk-1/CD34 double-positive cells towards the ischemic penumbra was increased in the exercise group. Furthermore, the induction of VEGF protein, microvessel density, decrease of infarct volumes and neurological recovery was significantly inhibited by daidzein. This study indicates that treadmill exercise reduces brain injury in stroke. Our findings suggest that the caveolin-1 pathway is involved in the regulation of VEGF in association with promoted angiogenesis in the ischemic penumbra of rat brains after treadmill exercise. The caveolin-1/VEGF signaling pathway may be a potential target for therapeutic intervention in rats following MCAO. (C) 2014 Elsevier BM. All rights reserved.
C1 [Gao, Yong; Zhao, Yun; Pan, Jingzi; Yang, Liu; Huang, Tingting; Feng, Xiaomin; Li, Chao; Liang, Shujing; Zhou, Dingfu; Liu, Chan; Tu, Fengxia; Chen, Xiang] Wenzhou Med Univ, Affiliated Hosp 2, Phys Med & Rehabil Ctr, Wenzhou 325027, Zhejiang, Peoples R China.
[Gao, Yong; Zhao, Yun; Pan, Jingzi; Yang, Liu; Huang, Tingting; Feng, Xiaomin; Li, Chao; Liang, Shujing; Zhou, Dingfu; Liu, Chan; Tu, Fengxia; Chen, Xiang] Wenzhou Med Univ, Yuying Childrens Hosp, Wenzhou 325027, Zhejiang, Peoples R China.
[Tao, Cai] NIH, Expt Med Sect, NIDCR, Bethesda, MD 20892 USA.
RP Chen, X (reprint author), Wenzhou Med Univ, Affiliated Hosp 2, Phys Med & Rehabil Ctr, 109 Xuyuanxi Rd, Wenzhou 325027, Zhejiang, Peoples R China.
EM chemxiangnj2005@aliyun.com.cn
FU Science Technology Department of Zhejiang Province funded Qianjiang
talents project [2009R10024]; Natural Science Foundation of Zhejiang
Province funded project [Y12H170002]
FX This work was supported partially by The Science Technology Department
of Zhejiang Province funded Qianjiang talents project (No.2009R10024)
and The Natural Science Foundation of Zhejiang Province funded project
(No. Y12H170002). We also appreciate the wonderful technical assistance
of the Laboratory Animal Centre of Wenzhou Medical University and the
Laboratory Centre of the Second Affiliated Hospital & Yuying Children's
Hospital of Wenzhou Medical University for this study.
NR 33
TC 12
Z9 14
U1 3
U2 25
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 OCT 17
PY 2014
VL 1585
BP 83
EP 90
DI 10.1016/j.brainres.2014.08.032
PG 8
WC Neurosciences
SC Neurosciences & Neurology
GA AR8QS
UT WOS:000343840300008
PM 25148708
ER
PT J
AU Shytuhina, A
Pristatsky, P
He, J
Casimiro, DR
Schwartz, RM
Hoang, V
Ha, S
AF Shytuhina, Anastasija
Pristatsky, Pavlo
He, Jian
Casimiro, Danilo R.
Schwartz, Richard M.
Hoang, Van M.
Ha, Sha
TI Development and application of a reversed-phase high-performance liquid
chromatographic method for quantitation and characterization of a
Chikungunya virus-like particle vaccine
SO JOURNAL OF CHROMATOGRAPHY A
LA English
DT Article
DE RP-HPLC; Vaccine; VLP; Chikungunya; CHIKV; Analytical characterization
ID SITE-DIRECTED MUTATIONS; N-LINKED GLYCOSYLATION; HYDROPHOBIC PROTEINS;
VIRAL GLYCOPROTEINS; HPLC; HEMAGGLUTININ; OPTIMIZATION; PURIFICATION;
BACULOVIRUS; INFECTION
AB To effectively support the development of a Chikungunya (CHIKV) virus-like particle (VLP) vaccine, a sensitive and robust high-performance liquid chromatography (HPLC) method that can quantitate CHIKV VLPs and monitor product purity throughout the manufacturing process is needed. We developed a sensitive reversed-phase HPLC (RP-HPLC) method that separates capsid, E1, and E2 proteins in CHIKV VLP vaccine with good resolution. Each protein component was verified by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and matrix-assisted laser desorption/ionization time-of-flight (MALDI-ToF) mass spectrometry (MS). The post-translational modifications on the viral glycoproteins E1 and E2 were further identified by intact protein mass measurements with liquid chromatography mass spectrometry (LC-MS). The RP-HPLC method has a linear range of 0.51-12 mu g protein, an accuracy of 96-106% and a precision of 12% RSD, suitable for vaccine product release testing. In addition, we demonstrated that the RP-HPLC method is useful for characterizing viral glycoprotein post-translational modifications, monitoring product purity during process development and assessing product stability during formulation development. Published by Elsevier B.V.
C1 [Shytuhina, Anastasija; Pristatsky, Pavlo; He, Jian; Casimiro, Danilo R.; Hoang, Van M.; Ha, Sha] Merck Res Labs, Vaccine Bioproc Res & Dev, West Point, PA 19486 USA.
[Schwartz, Richard M.] NIAID, Vaccine Prod Program, Vaccine Res Ctr, NIH, Gaithersburg, MD 20878 USA.
RP Ha, S (reprint author), Merck Res Labs, Vaccine Bioproc Res & Dev, West Point, PA 19486 USA.
EM sha_ha@merck.com
FU Intramural NIH HHS [Z99 AI999999]
NR 33
TC 4
Z9 4
U1 2
U2 17
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0021-9673
EI 1873-3778
J9 J CHROMATOGR A
JI J. Chromatogr. A
PD OCT 17
PY 2014
VL 1364
BP 192
EP 197
DI 10.1016/j.chroma.2014.05.087
PG 6
WC Biochemical Research Methods; Chemistry, Analytical
SC Biochemistry & Molecular Biology; Chemistry
GA AR1QH
UT WOS:000343359200021
PM 25234500
ER
PT J
AU Gossa, S
Nayak, D
Zinselmeyer, BH
McGavern, DB
AF Gossa, Selamawit
Nayak, Debasis
Zinselmeyer, Bernd H.
McGavern, Dorian B.
TI Development of an Immunologically Tolerated Combination of Fluorescent
Proteins for In vivo Two-photon Imaging
SO SCIENTIFIC REPORTS
LA English
DT Article
ID RED; MICROSCOPY; ORANGE; MICE; AEQUOREA; ANTIGEN; BRIGHT
AB Combinations of fluorescent proteins (FPs) are routinely used for multi-parameter in vivo imaging experiments to visualize tagged proteins or cell populations of interest. Studies involving FPs are often limited by spectral overlap, toxicity, relative quantum efficiency, and the potential for immunological rejection upon transfer into a non-tolerant recipient. Here we evaluate the immunologic visibility of several commonly used FPs by the murine immune system and identify a spectrally compatible, immunologically tolerated combination of FPs well suited for in vivo two-photon imaging.
C1 [Gossa, Selamawit; Nayak, Debasis; Zinselmeyer, Bernd H.; McGavern, Dorian B.] NINDS, NIH, Bethesda, MD 20892 USA.
RP McGavern, DB (reprint author), NINDS, NIH, Bethesda, MD 20892 USA.
EM mcgavernd@mail.nih.gov
OI McGavern, Dorian/0000-0001-9568-545X
FU National Institutes of Health (NIH) intramural program; NIH Intramural
Competitive Fellowship
FX This work was supported by National Institutes of Health (NIH)
intramural program. D. Nayak was supported by a NIH Intramural
Competitive Fellowship. We would like to thank Dr. James Pickel and the
NIMH Transgenic Core Facility for their assistance in generating the new
transgenic fluorescent protein reporter mice described in this
manuscript.
NR 31
TC 2
Z9 2
U1 2
U2 7
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2045-2322
J9 SCI REP-UK
JI Sci Rep
PD OCT 17
PY 2014
VL 4
AR 6664
DI 10.1038/srep06664
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AR0WO
UT WOS:000343294300003
PM 25322934
ER
PT J
AU Badirou, I
Pan, JJ
Legrand, C
Wang, AB
Lordier, L
Boukour, S
Roy, A
Vainchenker, W
Chang, YH
AF Badirou, Idinath
Pan, Jiajia
Legrand, Celine
Wang, Aibing
Lordier, Larissa
Boukour, Siham
Roy, Anita
Vainchenker, William
Chang, Yunhua
TI Carboxyl-terminal-dependent recruitment of nonmuscle myosin II to
megakaryocyte contractile ring during polyploidization
SO BLOOD
LA English
DT Article
ID ENDOMITOTIC MEGAKARYOCYTES; PROPLATELET FORMATION; ISOFORM; DEFECTS;
CELLS; TAIL; MICE; FORM
AB Endomitosis is auniquemegakaryocyte (MK) differentiation process that is the consequence of a late cytokinesis failure associated with a contractile ring defect. Evidence from in vitro studies has revealed the distinct roles of 2 nonmuscle myosin IIs (NMIIs) on MK endomitosis: only NMII-B (MYH10), but not NMII-A (MYH9), is localized in the MK contractile ring and implicated in mitosis/endomitosis transition. Here, we studied 2 transgenic mouse models in which nonmuscle myosin heavy chain (NMHC) II-A was genetically replaced either by II-B or by a chimeric NMHCII that combined the head domain of II-A with the rod and tail domains of II-B. This study provides in vivo evidence on the specific role of NMII-B on MK polyploidization. It demonstrates that the carboxyl-terminal domain of the heavy chains determines myosin II localization to the MK contractile ring and is responsible for the specific role of NMII-B in MK polyploidization.
C1 [Badirou, Idinath; Pan, Jiajia; Legrand, Celine; Lordier, Larissa; Boukour, Siham; Roy, Anita; Vainchenker, William; Chang, Yunhua] Inst Gustave Roussy, INSERM UMR1009, Villejuif, France.
[Badirou, Idinath; Pan, Jiajia; Legrand, Celine; Lordier, Larissa; Boukour, Siham; Roy, Anita; Vainchenker, William; Chang, Yunhua] Univ Paris 11, UMR 1009, Le Kremlin Bicetre, France.
[Badirou, Idinath; Pan, Jiajia; Legrand, Celine; Lordier, Larissa; Boukour, Siham; Roy, Anita; Vainchenker, William; Chang, Yunhua] Inst Gustave Roussy, UMR 1009, Villejuif, France.
[Wang, Aibing] NHLBI, Mol Cardiol Lab, NIH, Bethesda, MD 20892 USA.
RP Chang, YH (reprint author), Inst Gustave Roussy, INSERM UMR1009, Villejuif, France.
EM Yunhua.chang@gustaveroussy.fr
FU INSERM; Agence Nationale de la Recherche (ANR Jeune Chercheur); la Ligue
Nationale Contre le Cancer (Equipe labellisee); ANR; China Scholarship
Council; la Societe Francaise d'Hematologie; la Fondation de la
Recherche Medicale (FRM)
FX This work was supported by INSERM, by the Agence Nationale de la
Recherche (ANR Jeune Chercheur) (Y.C.), and by grants from la Ligue
Nationale Contre le Cancer (Equipe labellisee). I.B. was supported by
ANR, and J.P. by the China Scholarship Council and la Societe Francaise
d'Hematologie. A.R. is supported by a grant from la Fondation de la
Recherche Medicale (FRM).
NR 18
TC 2
Z9 2
U1 1
U2 3
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA
SN 0006-4971
EI 1528-0020
J9 BLOOD
JI Blood
PD OCT 16
PY 2014
VL 124
IS 16
BP 2564
EP 2568
DI 10.1182/blood-2014-06-584995
PG 5
WC Hematology
SC Hematology
GA AY3AD
UT WOS:000347456100015
PM 25185263
ER
PT J
AU Tang, WH
Wang, HS
Claudio, E
Tassi, I
Ha, HL
Saret, S
Siebenlist, U
AF Tang, Wanhu
Wang, Hongshan
Claudio, Estefania
Tassi, Ilaria
Ha, Hye-lin
Saret, Sun
Siebenlist, Ulrich
TI The Oncoprotein and Transcriptional Regulator Bcl-3 Governs Plasticity
and Pathogenicity of Autoimmune T Cells
SO IMMUNITY
LA English
DT Article
ID ROR-GAMMA-T; NF-KAPPA-B; CANDIDATE PROTOONCOGENE BCL-3; GERMINAL CENTER
REACTIONS; CYTOKINE GM-CSF; INTESTINAL INFLAMMATION; SPLENIC
MICROARCHITECTURE; EXPERIMENTAL COLITIS; MEDIATED-IMMUNITY;
CROHNS-DISEASE
AB Bcl-3 is an atypical member of the I kappa B family that modulates transcription in the nucleus via association with p50 (NF-kappa B1) or p52 (NF-kappa B2) homodimers. Despite evidence attesting to the overall physiologic importance of Bcl-3, little is known about its cell-specific functions or mechanisms. Here we demonstrate a T-cell-intrinsic function of Bcl-3 in autoimmunity. Bcl-3-deficient T cells failed to induce disease in T cell transfer-induced colitis and experimental autoimmune encephalomyelitis. The protection against disease correlated with a decrease in Th1 cells that produced the cytokines IFN-gamma and GM-CSF and an increase in Th17 cells. Although differentiation into Th1 cells was not impaired in the absence of Bcl-3, differentiated Th1 cells converted to less-pathogenic Th17-like cells, in part via mechanisms involving expression of the ROR gamma t transcription factor. Thus, Bcl-3 constrained Th1 cell plasticity and promoted pathogenicity by blocking conversion to Th17-like cells, revealing a unique type of regulation that shapes adaptive immunity.
C1 [Tang, Wanhu; Wang, Hongshan; Claudio, Estefania; Tassi, Ilaria; Ha, Hye-lin; Saret, Sun; Siebenlist, Ulrich] NIAID, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA.
RP Siebenlist, U (reprint author), NIAID, Lab Mol Immunol, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM usiebenlist@niaid.nih.gov
FU Intramural Research Program of NIAID; NIH
FX We thank L. Glimcher and V. Lazarevic for providing the Rorc-luciferase
reporter and the GFP-ROR gamma t retrovirus, E. Shevach for advice with
the EAE model, H. Takayanagi and K. Okamoto for the IL-17-driven
luciferase reporter, and BD Biosciences for alpha-p19 antibodies.
Research was supported by the Intramural Research Program of NIAID, NIH.
NR 43
TC 10
Z9 10
U1 1
U2 13
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 OCT 16
PY 2014
VL 41
IS 4
BP 555
EP 566
DI 10.1016/j.immuni.2014.09.017
PG 12
WC Immunology
SC Immunology
GA AU3HY
UT WOS:000345504300010
PM 25367572
ER
PT J
AU Cho, HJ
Yu, J
Xie, CS
Rudrabhatla, P
Chen, X
Wu, JB
Parisiadou, L
Liu, GX
Sun, LX
Ma, B
Ding, JH
Liu, ZH
Cai, HB
AF Cho, Hyun Jin
Yu, Jia
Xie, Chengsong
Rudrabhatla, Parvathi
Chen, Xi
Wu, Junbing
Parisiadou, Loukia
Liu, Guoxiang
Sun, Lixin
Ma, Bo
Ding, Jinhui
Liu, Zhihua
Cai, Huaibin
TI Leucine-rich repeat kinase 2 regulates Sec16A at ER exit sites to allow
ER-Golgi export
SO EMBO JOURNAL
LA English
DT Article
DE dendritic ERES (dERES); ER exit sites (ERES); ER-Golgi transport;
Leucine-rich repeat kinase 2 (LRRK2); Sec16A
ID GENOME-WIDE ASSOCIATION; PARKINSONS-DISEASE; ENDOPLASMIC-RETICULUM;
ALPHA-SYNUCLEIN; TRANSITIONAL ER; NMDA RECEPTORS; NONREDUNDANT
FUNCTIONS; PLEOMORPHIC PATHOLOGY; SYNAPTIC PLASTICITY; LIVING CELLS
AB Leucine-rich repeat kinase 2 (LRRK2) has been associated with Parkinson's disease (PD) and other disorders. However, its normal physiological functions and pathogenic properties remain elusive. Here we show that LRRK2 regulates the anterograde ER-Golgi transport through anchoring Sec16A at the endoplasmic reticulum exit sites (ERES). LRRK2 interacted and co-localized with Sec16A, a key protein in the formation of ERES. Lrrk2 depletion caused a dispersion of Sec16A from ERES and impaired ER export. In neurons, LRRK2 and Sec16A showed extensive co-localization at the dendritic ERES (dERES) that locally regulate the transport of proteins to the dendritic spines. A loss of Lrrk2 affected the association of Sec16A with dERES and impaired the activity-dependent targeting of glutamate receptors onto the cell/synapse surface. Furthermore, the PD-related LRRK2 R1441C missense mutation in the GTPase domain interfered with the interaction of LRRK2 with Sec16A and also affected ER-Golgi transport, while LRRK2 kinase activity was not required for these functions. Therefore, our findings reveal a new physiological function of LRRK2 in ER-Golgi transport, suggesting ERES dysfunction may contribute to the pathogenesis of PD.
C1 [Cho, Hyun Jin; Yu, Jia; Xie, Chengsong; Chen, Xi; Wu, Junbing; Parisiadou, Loukia; Liu, Guoxiang; Sun, Lixin; Ma, Bo; Cai, Huaibin] NIA, Transgen Sect, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
[Rudrabhatla, Parvathi] NINDS, Neurochem Lab, Bethesda, MD 20892 USA.
[Rudrabhatla, Parvathi] NINDS, Neurobiol Lab, Bethesda, MD 20892 USA.
[Ding, Jinhui] NIAID, Bioinformat Core, Neurogenet Lab, Bethesda, MD 20892 USA.
[Liu, Zhihua] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA.
[Liu, Zhihua] Chinese Acad Sci, Inst Biophys, Beijing 100080, Peoples R China.
RP Liu, ZH (reprint author), NIAID, Immunol Lab, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM zhihualiu@ibp.ac.cn; caih@mail.nih.gov
RI MA, BO/L-6502-2015
OI MA, BO/0000-0001-5922-666X
FU Intramural Research Program of National Institute on Aging [AG000944];
National Institute of Allergy and Infectious Diseases
FX This work was supported in part by The Intramural Research Programs of
National Institute on Aging (AG000944) and National Institute of Allergy
and Infectious Diseases. We thank Dr. Michael Lenardo of NIAID for his
support in identification of LRRK2-interacting proteins, Dr. Eric
Anderson of Proteomics and Mass Spectrometry Facility, National
Institute of Diabetes and Digestive and Kidney Diseases for Mass
Spectrometry analysis, Dr. Haining Zhong for providing mCherry
expression vector, Dr. Craig Blackstone of National Institute of
Neurological Disorders and Stroke (NINDS) for providing RFP-Sec61 beta
plasmid, and Drs. Peng Cheng and Randy Sheckman for their input on in
vitro budding assay.
NR 72
TC 17
Z9 17
U1 2
U2 5
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0261-4189
EI 1460-2075
J9 EMBO J
JI Embo J.
PD OCT 16
PY 2014
VL 33
IS 20
BP 2314
EP 2331
DI 10.15252/embj.201487807
PG 18
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA AR9UE
UT WOS:000343922500006
PM 25201882
ER
PT J
AU Wade, BSC
Joshi, SH
Reuter, M
Blumenthal, JD
Toga, AW
Thompson, PM
Giedd, JN
AF Wade, Benjamin S. C.
Joshi, Shantanu H.
Reuter, Martin
Blumenthal, Jonathan D.
Toga, Arthur W.
Thompson, Paul M.
Giedd, Jay N.
TI Effects of sex chromosome dosage on corpus callosum morphology in
supernumerary sex chromosome aneuploidies
SO BIOLOGY OF SEX DIFFERENCES
LA English
DT Article
DE Corpus callosum; Sex chromosomes; Aneuploidies; Statistical shape
analysis; Sexual differentiation
ID DISTANCE MATRIX ANALYSIS; KLINEFELTER-SYNDROME; MOTOR DEVELOPMENT;
X-CHROMOSOME; BRAIN; XXY; DEFICITS; MALES; XXXXY; SCHIZOPHRENIA
AB Background: Supernumerary sex chromosome aneuploidies (sSCA) are characterized by the presence of one or more additional sex chromosomes in an individual's karyotype; they affect around 1 in 400 individuals. Although there is high variability, each sSCA subtype has a characteristic set of cognitive and physical phenotypes. Here, we investigated the differences in the morphometry of the human corpus callosum (CC) between sex-matched controls 46, XY (N = 99), 46, XX (N = 93), and six unique sSCA karyotypes: 47,XYY (N = 29), 47,XXY (N = 58), 48,XXYY (N = 20), 47,XXX (N = 30), 48,XXXY (N = 5), and 49,XXXXY (N = 6).
Methods: We investigated CC morphometry using local and global area, local curvature of the CC boundary, and between-landmark distance analysis (BLDA). We hypothesized that CC morphometry would vary differentially along a proposed spectrum of Y:X chromosome ratio with supernumerary Y karyotypes having the largest CC areas and supernumerary X karyotypes having significantly smaller CC areas. To investigate this, we defined an sSCA spectrum based on a descending Y:X karyotype ratio: 47,XYY, 46,XY, 48,XXYY, 47,XXY, 48,XXXY, 49,XXXXY, 46,XX, 47,XXX. We similarly explored the effects of both X and Y chromosome numbers within sex.
Results of shape-based metrics were analyzed using permutation tests consisting of 5,000 iterations. Results: Several subregional areas, local curvature, and BLDs differed between groups. Moderate associations were found between area and curvature in relation to the spectrum and X and Y chromosome counts. BLD was strongly associated with X chromosome count in both male and female groups.
Conclusions: Our results suggest that X-and Y-linked genes have differential effects on CC morphometry. To our knowledge, this is the first study to compare CC morphometry across these extremely rare groups.
C1 [Wade, Benjamin S. C.; Thompson, Paul M.] Univ So Calif, Inst Neuro Imaging & Informat, Imaging Genet Ctr, Marina Del Rey, CA 90292 USA.
[Joshi, Shantanu H.] Univ Calif Los Angeles, Ahmanson Lovelace Brain Mapping Ctr, Dept Neurol, Los Angeles, CA 90095 USA.
[Reuter, Martin] Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA.
[Toga, Arthur W.] Univ So Calif, Keck Sch Med, Inst Neuro Imaging & Informat, Los Angeles, CA 90032 USA.
[Blumenthal, Jonathan D.; Giedd, Jay N.] NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA.
RP Wade, BSC (reprint author), Univ So Calif, Inst Neuro Imaging & Informat, Imaging Genet Ctr, 4676 Admiralty Way, Marina Del Rey, CA 90292 USA.
EM Benjamin.SC.Wade@gmail.com
RI Giedd, Jay/J-9644-2015
OI Giedd, Jay/0000-0003-2002-8978
FU National Science Foundation [DGE-0707424]
FX This material is based upon work supported by the National Science
Foundation Graduate Research Fellowship under Grant No. DGE-0707424. Any
opinion, findings, and conclusions or recommendations expressed in this
material are those of the authors and do not necessarily reflect the
views of the National Science Foundation. Linda Wade contributed
significantly to the editing of this manuscript.
NR 58
TC 2
Z9 2
U1 2
U2 14
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 2042-6410
J9 BIOL SEX DIFFER
JI Biol. Sex Differ.
PD OCT 16
PY 2014
VL 5
AR 16
DI 10.1186/s13293-014-0016-4
PG 18
WC Endocrinology & Metabolism; Genetics & Heredity
SC Endocrinology & Metabolism; Genetics & Heredity
GA AR7QJ
UT WOS:000343774100001
PM 25780557
ER
PT J
AU Meyerson, JR
Kumar, J
Chittori, S
Rao, P
Pierson, J
Bartesaghi, A
Mayer, ML
Subramaniam, S
AF Meyerson, Joel R.
Kumar, Janesh
Chittori, Sagar
Rao, Prashant
Pierson, Jason
Bartesaghi, Alberto
Mayer, Mark L.
Subramaniam, Sriram
TI Structural mechanism of glutamate receptor activation and
desensitization
SO NATURE
LA English
DT Article
ID LIGAND-BINDING DOMAIN; EM STRUCTURE DETERMINATION; AMPA RECEPTORS;
ION-CHANNEL; CRYSTAL-STRUCTURES; ELECTRON CRYOMICROSCOPY; KAINATE
RECEPTORS; TERMINAL DOMAIN; RESOLUTION; GLUR2
AB Ionotropic glutamate receptors are ligand-gated ion channels that mediate excitatory synaptic transmission in the vertebrate brain. To gain a better understanding of how structural changes gate ion flux across the membrane, we trapped rat AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) and kainate receptor subtypes in their major functional states and analysed the resulting structures using cryo-electron microscopy. We show that transition to the active state involves a 'corkscrew' motion of the receptor assembly, driven by closure of the ligand-binding domain. Desensitization is accompanied by disruption of the amino-terminal domain tetramer in AMPA, but not kainate, receptors with a two-fold to four-fold symmetry transition in the ligand-binding domains in both subtypes. The 7.6 angstrom structure of a desensitized kainate receptor shows how these changes accommodate channel closing. These findings integrate previous physiological, biochemical and structural analyses of glutamate receptors and provide a molecular explanation for key steps in receptor gating.
C1 [Meyerson, Joel R.; Rao, Prashant; Bartesaghi, Alberto; Subramaniam, Sriram] NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Kumar, Janesh; Chittori, Sagar; Mayer, Mark L.] NICHD, Lab Cellular & Mol Neurophysiol, Porter Neurosci Res Ctr, NIH, Bethesda, MD 20892 USA.
[Pierson, Jason] FEI Co, Hillsboro, OR 97124 USA.
RP Subramaniam, S (reprint author), NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM mayerm@mail.nih.gov; ss1@nih.gov
OI Chittori, Sagar/0000-0003-1417-6552
FU NCI; NICHD, NIH; IATAP program at NIH; NIH-FEI Living Lab for Structural
Biology
FX This work was supported by the intramural programs of the NCI, and
NICHD, NIH, the IATAP program at NIH and the NIH-FEI Living Lab for
Structural Biology. We thank D. Bleakman, Eli Lilly and Company for the
gift of LY451646, Y. J. Eun for discussions on preparation of cryo-EM
samples, X. Wu for discussions on fitting crystallographic coordinates
to cryo-EM maps, D. Bliss for assistance with preparing schematic
illustrations, L. Earl, M. J. Borgnia and J. L. S. Milne for
discussions, and S. Fellini, S. Chacko and their colleagues for
continued support with use of the Biowulf cluster for computing at NIH.
NR 53
TC 74
Z9 74
U1 5
U2 51
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 OCT 16
PY 2014
VL 514
IS 7522
BP 328
EP +
DI 10.1038/nature13603
PG 19
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AQ7JH
UT WOS:000342988600043
PM 25119039
ER
PT J
AU Martin, D
Abba, MC
Molinolo, AA
Vitale-Cross, L
Wang, ZY
Zaida, M
Delic, NC
Samuels, Y
Lyons, JG
Gutkind, JS
AF Martin, Daniel
Abba, Martin C.
Molinolo, Alfredo A.
Vitale-Cross, Lynn
Wang, Zhiyong
Zaida, Moraima
Delic, Naomi C.
Samuels, Yardena
Lyons, J. Guy
Gutkind, J. Silvio
TI The head and neck cancer cell oncogenome: a platform for the development
of precision molecular therapies
SO ONCOTARGET
LA English
DT Article
DE HNSCC; Sequencing; Exome; RNAseq; Cancer
ID TUMOR-SUPPRESSOR GENE; FACTOR-KAPPA-B; HUMAN-PAPILLOMAVIRUS;
NEXT-GENERATION; SEQUENCING DATA; CARCINOMA; MUTATIONS; PATHWAY; LINES;
METHYLATION
AB The recent elucidation of the genomic landscape of head and neck squamous cell carcinoma (HNSCC) has provided a unique opportunity to develop selective cancer treatment options. These efforts will require the establishment of relevant HNSCC models for preclinical testing. Here, we performed full exome and transcriptome sequencing of a large panel of HNSCC-derived cells from different anatomical locations and human papillomavirus (HPV) infection status. These cells exhibit typical mutations in TP53, FAT1, CDK2NA, CASP8, and NOTCH1, and copy number variations (CNVs) and mutations in PIK3CA, HRAS, and PTEN that reflect the widespread activation of the PI3K-mTOR pathway. SMAD4 alterations were observed that may explain the decreased tumor suppressive effect of TGF-beta in HNSCC. Surprisingly, we identified HPV+ HNSCC cells harboring TP53 mutations, and documented aberrant TP53 expression in a subset of HPV+ HNSCC cases. This analysis also revealed that most HNSCC cells harbor multiple mutations and CNVs in epigenetic modifiers (e.g., EP300, CREBP, MLL1, MLL2, MLL3, KDM6A, and KDM6B) that may contribute to HNSCC initiation and progression. These genetically-defined experimental HNSCC cellular systems, together with the identification of novel actionable molecular targets, may now facilitate the pre-clinical evaluation of emerging therapeutic agents in tumors exhibiting each precise genomic alteration.
C1 [Martin, Daniel; Molinolo, Alfredo A.; Vitale-Cross, Lynn; Wang, Zhiyong; Zaida, Moraima; Gutkind, J. Silvio] NIH, Oral & Pharyngeal Canc Branch, Bethesda, MD 20892 USA.
[Abba, Martin C.] Univ Nacl La Plata, Fac Ciencias Med, CINIBA, La Plata, Buenos Aires, Argentina.
[Samuels, Yardena] Weizmann Inst Sci, Dept Mol Cell Biol, IL-76100 Rehovot, Israel.
[Delic, Naomi C.; Lyons, J. Guy] Univ Sydney, Camperdown, NSW, Australia.
[Delic, Naomi C.; Lyons, J. Guy] Royal Prince Alfred Hosp, Canc Serv, Camperdown, NSW 2050, Australia.
RP Gutkind, JS (reprint author), NIH, Oral & Pharyngeal Canc Branch, Bldg 10, Bethesda, MD 20892 USA.
EM sg39v@nih.gov
RI Lyons, Guy/B-1319-2012;
OI Lyons, Guy/0000-0002-4835-4663; Abba, Martin/0000-0002-9206-2369
FU National Institutes of Health Intramural AIDS Targeted Antiviral
Program; National Institute of Dental and Craniofacial Research; NHGRI;
Human Frontiers Science Program [RGP0041-2011]; Cancer Council NSW
[RG10-09]; NHMRC [1026232]; Israel Science Foundation [1604/13, 877/13];
ERC [StG-335377]
FX This research was supported by a National Institutes of Health
Intramural AIDS Targeted Antiviral Program, the National Institute of
Dental and Craniofacial Research, NHGRI, Human Frontiers Science Program
grant RGP0041-2011, Cancer Council NSW grant RG10-09 and NHMRC Project
Grant 1026232. We would also like to thank the NIH Intramural Sequencing
Center (NISC), for their continued technical support and scientific
advice. The results shown here are in part based upon data generated by
the TCGA Research Network (cancergenome.nih.gov) and the 1000 Genomes
Consortium (www.1000genomes.org). We apologize to colleagues whose
primary research papers may not have been cited due to space
constraints.; YS is supported by Gideon Hamburger, the Israel Science
Foundation grant numbers 1604/13 and 877/13 and the ERC (StG-335377).
NR 82
TC 31
Z9 31
U1 0
U2 12
PU IMPACT JOURNALS LLC
PI ALBANY
PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA
SN 1949-2553
J9 ONCOTARGET
JI Oncotarget
PD OCT 15
PY 2014
VL 5
IS 19
BP 8906
EP 8923
PG 18
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA AZ1ZL
UT WOS:000348033800007
PM 25275298
ER
PT J
AU Kavarthapu, R
Morris, CHT
Dufau, ML
AF Kavarthapu, Raghuveer
Morris, Chon-Hwa Tsai
Dufau, Maria L.
TI Prolactin induces up-regulation of its cognate receptor in breast cancer
cells via transcriptional activation of its generic promoter by
cross-talk between ERa and STAT5
SO ONCOTARGET
LA English
DT Article
DE prolactin; prolactin receptor; ERa; STAT5; Sp1/ C/EBP beta; signal
transduction; breast cancer
ID ESTROGEN-RECEPTOR; ALPHA; COMPLEX; PHOSPHORYLATION; RESISTANCE;
TRANSDUCER; EXPRESSION; KINASES; LIGAND; TUMORS
AB Prolactin (PRL) serves a critical role in breast cancer progression via activation of its cognate receptor. These studies reveal up-regulation of PRLR gene expression by PRL in absence of estradiol in MCF-7 and T47D breast cancer cells. PRL/PRLR via activation of STAT5 that binds a GAS-element in the PRLR gene and the participation of ERa stimulates PRLR transcription/expression. PRL/PRLR induces phosphorylation of ERa through the JAK2/PI3K/MAPK/ERK and JAK2/HER2 activated pathways. The increased recruitment of phospho-ERa, induced by PRL to Sp1 and C/EBPa at PRLR promoter sites, is essential for PRL-induced PRLR transcription. This recruitment is prevented by blockade of PRL expression using RNA interference or ERa phosphorylation with specific inhibitors of PI3K and ERK. Direct evidence is provided for local actions of PRL, independent of estradiol, in the up-regulation of PRLR transcription/expression by an activation-loop between STAT5 and the phospho-ERa/Sp1/C/EBP beta complex with requisite participation of signaling mechanisms. PRL's central role in the up-regulation of PRLR maximizes the action of the endogenous hormone. This study offers mechanistically rational basis for invasiveness fueled by prolactin in refractory states to adjuvant therapies in breast cancer.
C1 [Kavarthapu, Raghuveer; Morris, Chon-Hwa Tsai; Dufau, Maria L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Mol Endocrinol, Program Dev Endocrinol & Genet, NIH, Bethesda, MD 20892 USA.
RP Dufau, ML (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Mol Endocrinol, Program Dev Endocrinol & Genet, NIH, Bethesda, MD 20892 USA.
EM dufaum@mail.nih.gov
OI kavarthapu, raghuveer/0000-0002-2198-2029
FU NIH Intramural Research Program through The Eunice Kennedy Shriver
National Institute Child Health and Human Development
FX This work was supported by the NIH Intramural Research Program through
The Eunice Kennedy Shriver National Institute Child Health and Human
Development.
NR 27
TC 8
Z9 9
U1 0
U2 1
PU IMPACT JOURNALS LLC
PI ALBANY
PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA
SN 1949-2553
J9 ONCOTARGET
JI Oncotarget
PD OCT 15
PY 2014
VL 5
IS 19
BP 9079
EP 9091
PG 13
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA AZ1ZL
UT WOS:000348033800021
PM 25193864
ER
PT J
AU Ardiani, A
Gameiro, SR
Kwilas, AR
Donahue, RN
Hodge, JW
AF Ardiani, Andressa
Gameiro, Sofia R.
Kwilas, Anna R.
Donahue, Renee N.
Hodge, James W.
TI Androgen deprivation therapy sensitizes prostate cancer cells to T-cell
killing through androgen receptor dependent modulation of the apoptotic
pathway
SO ONCOTARGET
LA English
DT Article
DE enzalutamide; abiraterone; ADT; cancer vaccine; immunogenic modulation;
prostate cancer; immunotherapy
ID INDUCED IMMUNOGENIC MODULATION; HUMAN CARCINOEMBRYONIC ANTIGEN;
ANTIANDROGEN THERAPY; COMBINATION THERAPY; INCREASED SURVIVAL; VACCINE;
CHEMOTHERAPY; RESISTANCE; IMMUNOTHERAPY; EXPRESSION
AB Despite recent advances in diagnosis and management, prostrate cancer remains the second most common cause of death from cancer in American men, after lung cancer. Failure of chemotherapies and hormone-deprivation therapies is the major cause of death in patients with castration-resistant prostate cancer (CRPC). Currently, the androgen inhibitors enzalutamide and abiraterone are approved for treatment of metastatic CRPC. Here we show for the first time that both enzalutamide and abiraterone render prostate tumor cells more sensitive to T cell-mediated lysis through immunogenic modulation, and that these immunomodulatory activities are androgen receptor (AR)-dependent. In studies reported here, the NAIP gene was significantly down-regulated in human prostate tumor cells treated in vitro and in vivo with enzalutamide. Functional analysis revealed that NAIP played a critical role in inducing CTL sensitivity. Amplification of AR is a major mechanism of resistance to androgen-deprivation therapy (ADT). Here, we show that enzalutamide enhances sensitivity to immune-mediated killing of prostate tumor cells that overexpress AR. The immunomodulatory properties of enzalutamide and abiraterone provide a rationale for their use in combination with immunotherapeutic agents in CRPC, especially for patients with minimal response to enzalutamide or abiraterone alone, or for patients who have developed resistance to ADT.
C1 [Ardiani, Andressa; Gameiro, Sofia R.; Kwilas, Anna R.; Donahue, Renee N.; Hodge, James W.] NCI, Lab Tumor Immunol & Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Hodge, JW (reprint author), NCI, Lab Tumor Immunol & Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM jh241d@nih.gov
RI Hodge, James/D-5518-2015
OI Hodge, James/0000-0001-5282-3154
FU Intramural Research Program of the Center for Cancer Research, National
Cancer Institute, National Institutes of Health
FX This research was supported by the Intramural Research Program of the
Center for Cancer Research, National Cancer Institute, National
Institutes of Health.
NR 46
TC 17
Z9 17
U1 0
U2 6
PU IMPACT JOURNALS LLC
PI ALBANY
PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA
SN 1949-2553
J9 ONCOTARGET
JI Oncotarget
PD OCT 15
PY 2014
VL 5
IS 19
BP 9335
EP 9348
PG 14
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA AZ1ZL
UT WOS:000348033800039
PM 25344864
ER
PT J
AU Vallieres, L
Dumas, A
Amiable, N
Vaccari, JPD
Chae, JJ
Keane, RW
Lacroix, S
AF Vallieres, Luc
Dumas, Aline
Amiable, Nathalie
Vaccari, Juan Pablo De Rivero
Chae, Jae Jin
Keane, Robert W.
Lacroix, Steve
TI The inflammasome pyrin contributes to pertussis toxin-induced IL-1 beta
synthesis, neutrophil intravascular crawling and autoimmune
encephalomyelitis
SO JOURNAL OF NEUROIMMUNOLOGY
LA English
DT Meeting Abstract
CT 12th International Congress of Neuroimmunology (ISNI)
CY NOV 09-13, 2014
CL Mainz, GERMANY
C1 [Vallieres, Luc; Dumas, Aline; Amiable, Nathalie; Lacroix, Steve] Univ Laval, CHU Quebec, Quebec City, PQ, Canada.
[Vaccari, Juan Pablo De Rivero] Univ Miami, Miami Project Cure Paralysis, Miami, FL USA.
[Chae, Jae Jin] NHGRI, Med Genet Branch, Bethesda, MD 20892 USA.
[Keane, Robert W.] Univ Miami, Dept Physiol & Biophys, Miami, FL USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0165-5728
EI 1872-8421
J9 J NEUROIMMUNOL
JI J. Neuroimmunol.
PD OCT 15
PY 2014
VL 275
IS 1-2
SI SI
MA 231
BP 72
EP 73
DI 10.1016/j.jneuroim.2014.08.191
PG 2
WC Immunology; Neurosciences
SC Immunology; Neurosciences & Neurology
GA AT8OK
UT WOS:000345192100183
ER
PT J
AU Billioux, BJ
Leibovitch, E
Brunetto, G
Dustin, I
Inati, S
Schreiber, J
Eze, C
Zaghloul, K
Jacobson, S
Theodore, W
AF Billioux, Bridgette Jeanne
Leibovitch, Emily
Brunetto, Giovanna
Dustin, Irene
Inati, Sara
Schreiber, John
Eze, Chigo
Zaghloul, Kareem
Jacobson, Steve
Theodore, William
TI Human Herpes Virus 6 in human epilepsy: Data from surgical resections
SO JOURNAL OF NEUROIMMUNOLOGY
LA English
DT Meeting Abstract
CT 12th International Congress of Neuroimmunology (ISNI)
CY NOV 09-13, 2014
CL Mainz, GERMANY
C1 [Billioux, Bridgette Jeanne; Leibovitch, Emily; Brunetto, Giovanna; Jacobson, Steve] NINDS, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA.
[Dustin, Irene; Schreiber, John; Eze, Chigo; Theodore, William] NINDS, Clin Epilepsy Sect, NIH, Bethesda, MD 20892 USA.
[Inati, Sara] NINDS, EEG Lab, NIH, Bethesda, MD 20892 USA.
[Zaghloul, Kareem] NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0165-5728
EI 1872-8421
J9 J NEUROIMMUNOL
JI J. Neuroimmunol.
PD OCT 15
PY 2014
VL 275
IS 1-2
SI SI
MA 163
BP 75
EP 75
DI 10.1016/j.jneuroim.2014.08.198
PG 1
WC Immunology; Neurosciences
SC Immunology; Neurosciences & Neurology
GA AT8OK
UT WOS:000345192100190
ER
PT J
AU Caruso, B
Brunetto, G
Massoud, R
Leibovitch, E
Jacobson, S
AF Caruso, Breanna
Brunetto, Giovanna
Massoud, Raya
Leibovitch, Emily
Jacobson, Steven
TI Droplet digital PCR for the precise quantification of HTLV-1
SO JOURNAL OF NEUROIMMUNOLOGY
LA English
DT Meeting Abstract
CT 12th International Congress of Neuroimmunology (ISNI)
CY NOV 09-13, 2014
CL Mainz, GERMANY
C1 [Caruso, Breanna; Brunetto, Giovanna; Massoud, Raya; Leibovitch, Emily; Jacobson, Steven] NINDS, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0165-5728
EI 1872-8421
J9 J NEUROIMMUNOL
JI J. Neuroimmunol.
PD OCT 15
PY 2014
VL 275
IS 1-2
SI SI
MA 422
BP 76
EP 76
DI 10.1016/j.jneuroim.2014.08.201
PG 1
WC Immunology; Neurosciences
SC Immunology; Neurosciences & Neurology
GA AT8OK
UT WOS:000345192100193
ER
PT J
AU Johnson, T
Tyagi, R
Lee, PR
Lee, MH
Johnson, KR
Kowalak, J
Medynets, M
Hategan, A
Nutman, TB
Sejvar, J
Makumbi, I
Aceng, JR
Dowell, SF
Nath, A
AF Johnson, Tory
Tyagi, Richa
Lee, Paul R.
Lee, Myoung-hwa
Johnson, Kory R.
Kowalak, Jeffery
Medynets, Marie
Hategan, Alina
Nutman, Thomas B.
Sejvar, James
Makumbi, Issa
Aceng, Jane R.
Dowell, Scott F.
Nath, Avindra
TI Detection of auto-antibodies to leiomodin-1 in patients with nodding
syndrome
SO JOURNAL OF NEUROIMMUNOLOGY
LA English
DT Meeting Abstract
CT 12th International Congress of Neuroimmunology (ISNI)
CY NOV 09-13, 2014
CL Mainz, GERMANY
C1 [Johnson, Tory; Tyagi, Richa; Lee, Paul R.; Lee, Myoung-hwa; Johnson, Kory R.; Kowalak, Jeffery; Medynets, Marie; Hategan, Alina; Nutman, Thomas B.; Nath, Avindra] NINDS, NIH, Bethesda, MD 20892 USA.
[Sejvar, James] Ctr Dis Control & Prevent, Natl Ctr Emerging & Zoonot Infect Dis, Atlanta, GA USA.
[Makumbi, Issa; Aceng, Jane R.] Minist Hlth, Kampala, Uganda.
[Dowell, Scott F.] Ctr Dis Control & Prevent, Ctr Global Hlth, Atlanta, GA USA.
NR 0
TC 4
Z9 4
U1 0
U2 1
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0165-5728
EI 1872-8421
J9 J NEUROIMMUNOL
JI J. Neuroimmunol.
PD OCT 15
PY 2014
VL 275
IS 1-2
SI SI
MA 444
BP 103
EP 103
DI 10.1016/j.jneuroim.2014.08.275
PG 1
WC Immunology; Neurosciences
SC Immunology; Neurosciences & Neurology
GA AT8OK
UT WOS:000345192100267
ER
PT J
AU Choi, E
Wang, TG
Nath, A
AF Choi, Elliot
Wang, Tongguang
Nath, Avindra
TI Activated T cells induce oligodendrocyte progenitor cells proliferation
by releasing VEGF-A
SO JOURNAL OF NEUROIMMUNOLOGY
LA English
DT Meeting Abstract
CT 12th International Congress of Neuroimmunology (ISNI)
CY NOV 09-13, 2014
CL Mainz, GERMANY
C1 [Choi, Elliot; Wang, Tongguang; Nath, Avindra] NINDS, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0165-5728
EI 1872-8421
J9 J NEUROIMMUNOL
JI J. Neuroimmunol.
PD OCT 15
PY 2014
VL 275
IS 1-2
SI SI
MA 527
BP 105
EP 106
DI 10.1016/j.jneuroim.2014.08.283
PG 2
WC Immunology; Neurosciences
SC Immunology; Neurosciences & Neurology
GA AT8OK
UT WOS:000345192100274
ER
PT J
AU Sousa, ADPA
Nicholas, R
Johnson, K
Darko, S
Price, D
Douek, D
Muraro, P
Jacobson, S
AF Sousa, Alessandra De Paula Alves
Nicholas, Richard
Johnson, Kory
Darko, Sam
Price, David
Douek, Daniel
Muraro, Paolo
Jacobson, Steven
TI Deep sequencing of T-cell receptor repertoire reveals enrichment of
highly expanded clonotypes in cerebrospinal fluid from multiple
sclerosis
SO JOURNAL OF NEUROIMMUNOLOGY
LA English
DT Meeting Abstract
CT 12th International Congress of Neuroimmunology (ISNI)
CY NOV 09-13, 2014
CL Mainz, GERMANY
C1 [Sousa, Alessandra De Paula Alves; Johnson, Kory; Jacobson, Steven] NINDS, NIH, Bethesda, MD 20892 USA.
[Nicholas, Richard; Muraro, Paolo] Univ London Imperial Coll Sci Technol & Med, IC, London, England.
[Darko, Sam; Douek, Daniel] NIAID, NIH, Bethesda, MD 20892 USA.
[Price, David] Cardiff Univ, Sch Med, Cardiff CF10 3AX, S Glam, Wales.
RI Price, David/C-7876-2013
OI Price, David/0000-0001-9416-2737
NR 0
TC 0
Z9 0
U1 0
U2 1
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0165-5728
EI 1872-8421
J9 J NEUROIMMUNOL
JI J. Neuroimmunol.
PD OCT 15
PY 2014
VL 275
IS 1-2
SI SI
MA 224
BP 197
EP 198
DI 10.1016/j.jneuroim.2014.08.530
PG 2
WC Immunology; Neurosciences
SC Immunology; Neurosciences & Neurology
GA AT8OK
UT WOS:000345192100519
ER
PT J
AU Herz, J
Mcgavern, D
AF Herz, Jasmin
Mcgavern, Dorian
TI Therapeutic antiviral T cells noncytopathically clear persistently
infected microglia following conversion into antigen presenting cells
SO JOURNAL OF NEUROIMMUNOLOGY
LA English
DT Meeting Abstract
CT 12th International Congress of Neuroimmunology (ISNI)
CY NOV 09-13, 2014
CL Mainz, GERMANY
C1 [Herz, Jasmin; Mcgavern, Dorian] NINDS, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0165-5728
EI 1872-8421
J9 J NEUROIMMUNOL
JI J. Neuroimmunol.
PD OCT 15
PY 2014
VL 275
IS 1-2
SI SI
MA 596
BP 220
EP 221
DI 10.1016/j.jneuroim.2014.08.592
PG 2
WC Immunology; Neurosciences
SC Immunology; Neurosciences & Neurology
GA AT8OK
UT WOS:000345192100581
ER
PT J
AU Lee, N
Leibovitch, E
Jacobson, S
AF Lee, Naomi
Leibovitch, Emily
Jacobson, Steven
TI Concentration dependent inhibitory effect of a nucleoside-based analog,
2,2-bis-hydroxymethyl-cyclopropavir, against human herpesvirus-6
replication
SO JOURNAL OF NEUROIMMUNOLOGY
LA English
DT Meeting Abstract
CT 12th International Congress of Neuroimmunology (ISNI)
CY NOV 09-13, 2014
CL Mainz, GERMANY
C1 [Lee, Naomi; Leibovitch, Emily; Jacobson, Steven] NINDS, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0165-5728
EI 1872-8421
J9 J NEUROIMMUNOL
JI J. Neuroimmunol.
PD OCT 15
PY 2014
VL 275
IS 1-2
SI SI
MA 167
BP 222
EP 223
DI 10.1016/j.jneuroim.2014.08.597
PG 2
WC Immunology; Neurosciences
SC Immunology; Neurosciences & Neurology
GA AT8OK
UT WOS:000345192100586
ER
PT J
AU Henning, TR
Butler, K
Hanson, D
Sturdevant, G
Ellis, S
Sweeney, EM
Mitchell, J
Deyounks, F
Phillips, C
Farshy, C
Fakile, Y
Papp, J
Secor, WE
Caldwell, H
Patton, D
McNicholl, JM
Kersh, EN
AF Henning, Tara R.
Butler, Katherine
Hanson, Debra
Sturdevant, Gail
Ellis, Shanon
Sweeney, Elizabeth M.
Mitchell, James
Deyounks, Frank
Phillips, Christi
Farshy, Carol
Fakile, Yetunde
Papp, John
Secor, W. Evan
Caldwell, Harlan
Patton, Dorothy
McNicholl, Janet M.
Kersh, Ellen N.
TI Increased Susceptibility to Vaginal Simian/Human Immunodeficiency Virus
Transmission in Pig-tailed Macaques Coinfected With Chlamydia
trachomatis and Trichomonas vaginalis
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
DE HIV risk; STI or STD; Chlamydia; Trichomonas; menstrual cycle; macaque;
HIV susceptibility model
ID SEXUALLY-TRANSMITTED-DISEASES; TENOFOVIR DISOPROXIL FUMARATE;
GENITAL-TRACT; PREEXPOSURE PROPHYLAXIS; HIV-1 TRANSMISSION;
MENSTRUAL-CYCLE; T-CELLS; INFECTION; MODEL; PROTECTION
AB Background. Sexually transmitted infections (STIs) are associated with an increased risk of human immunodeficiency virus (HIV) infection, but their biological effect on HIV susceptibility is not fully understood.
Methods. Female pig-tailed macaques inoculated with Chlamydia trachomatis and Trichomonas vaginalis (n = 9) or medium (controls; n = 7) were repeatedly challenged intravaginally with SHIVSF162p3. Virus levels were evaluated by real-time polymerase chain reaction, plasma and genital cytokine levels by Luminex assays, and STI clinical signs by colposcopy.
Results. Simian/HIV (SHIV) susceptibility was enhanced in STI-positive macaques (P = .04, by the log-rank test; relative risk, 2.5 [95% confidence interval, 1.1-5.6]). All STI-positive macaques were SHIV infected, whereas 3 controls (43%) remained uninfected. Moreover, relative to STI-negative animals, SHIV infections occurred earlier in the menstrual cycle in STI-positive macaques (P = .01, by the Wilcoxon test). Levels of inflammatory cytokines (interferon gamma, interleukin 6, and granulocyte colony-stimulating factor [G-CSF]) were higher in STI-positive macaques during STI inoculation and SHIV exposure periods (P <= .05, by the Wilcoxon test).
Conclusions. C. trachomatis and T. vaginalis infection increase the susceptibility to SHIV, likely because of prolonged genital tract inflammation. These novel data demonstrate a biological link between these nonulcerative STIs and the risk of SHIV infection, supporting epidemiological assocations of HIV and STIs. This study establishes a macaque model for studies of high-risk HIV transmission and prevention.
C1 [Henning, Tara R.; Butler, Katherine; Hanson, Debra; Sweeney, Elizabeth M.; Mitchell, James; Deyounks, Frank; McNicholl, Janet M.; Kersh, Ellen N.] Ctr Dis Control & Prevent, Div HIV AIDS Prevent, Atlanta, GA USA.
[Phillips, Christi; Farshy, Carol; Fakile, Yetunde; Papp, John] Ctr Dis Control & Prevent, Div STD Prevent, Atlanta, GA USA.
[Secor, W. Evan] Ctr Dis Control & Prevent, Div Parasit Dis & Malaria, Atlanta, GA USA.
[Ellis, Shanon] Total Solut, Atlanta, GA USA.
[Sturdevant, Gail; Caldwell, Harlan] NIAID, Lab Intracellular Parasites, Rocky Mt Labs, NIH, Hamilton, MT USA.
[Patton, Dorothy] Univ Washington, Dept Obstet & Gynecol, Seattle, WA 98195 USA.
RP Kersh, EN (reprint author), 1600 Clifton Rd NE,MS A-25, Atlanta, GA 30333 USA.
EM ekersh@cdc.gov
FU Centers for Disease Control and Prevention (CDC); National Institutes of
Health; CDC [Y1-AI-0681-02]
FX This work was supported by the Centers for Disease Control and
Prevention (CDC) and by the National Institutes of Health and CDC
(interagency agreement Y1-AI-0681-02).
NR 44
TC 16
Z9 17
U1 0
U2 3
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 OCT 15
PY 2014
VL 210
IS 8
BP 1239
EP 1247
DI 10.1093/infdis/jiu240
PG 9
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA AT0EI
UT WOS:000344609600009
PM 24755433
ER
PT J
AU Scherer, RW
Formby, C
Gold, S
Erdman, S
Rodhe, C
Carlson, M
Shade, D
Tucker, M
Sensinger, LM
Hughes, G
Conley, GS
Downey, N
Eades, C
Jylkka, M
Haber-Perez, A
Harper, C
Russell, SK
Sierra-Irizarry, B
Sullivan, M
AF Scherer, Roberta W.
Formby, Craig
Gold, Susan
Erdman, Sue
Rodhe, Charles
Carlson, Michele
Shade, Dave
Tucker, Melanie
Sensinger, Lee McCaffrey
Hughes, Gordon
Conley, George S.
Downey, Naomi
Eades, Cynthia
Jylkka, Margaret
Haber-Perez, Ada
Harper, Courtney
Russell, Shoshannah Kantor
Sierra-Irizarry, Benigno
Sullivan, Mark
CA Tinnitus Retraining Therapy Trial
TI The Tinnitus Retraining Therapy Trial (TRTT): study protocol for a
randomized controlled trial
SO TRIALS
LA English
DT Article
DE Randomized clinical trial; Tinnitus; Tinnitus retraining therapy
ID HANDICAP INVENTORY; MASKING
AB Background: Subjective tinnitus is the perception of sound in the absence of a corresponding external sound for which there is no known medical etiology. For a minority of individuals with tinnitus, the condition impacts their ability to lead a normal lifestyle and is severely debilitating. There is no known cure for tinnitus, so current therapy focuses on reducing the effect of tinnitus on the patient's quality of life. Tinnitus retraining therapy (TRT) uses nonpsychiatric tinnitus-specific educational counseling and sound therapy in a habituation-based protocol to reduce the patient's tinnitus-evoked negative reaction to, and awareness of, the tinnitus, with the ultimate goal of reducing the tinnitus impact on the patient's quality of life. Some studies support the efficacy of TRT, but no trial to date has compared TRT with the current standard of care or evaluated the separate contributions of TRT counseling and sound therapy. The Tinnitus Retraining Therapy Trial (TRTT) is a randomized, double-blind, placebo-controlled, multicenter trial for individuals with intolerable tinnitus.
Methods/design: The TRTT is enrolling active-duty and retired military personnel and their dependents with functionally adequate hearing sensitivity and severe tinnitus at US Air Force, Navy, and Army medical centers. Eligible study participants are randomized to TRT, partial TRT, or standard care to determine the efficacy of TRT and its components (TRT counseling and sound therapy). The primary outcome is change in score on the Tinnitus Questionnaire assessed longitudinally between baseline and follow-up (3, 6, 12, and 18 months following treatment). Secondary outcomes include subscale score changes in the Tinnitus Questionnaire, overall and subscale score changes in the Tinnitus Functional Index and Tinnitus Handicap Inventory, and change in the visual analog scale of the TRT Interview Form. Audiological outcomes include tinnitus pitch and loudness match and measures of loudness discomfort levels. The incidence of depression as a safety measure is assessed at each visit using the Beck Depression Inventory Fast Screen.
C1 [Scherer, Roberta W.; Rodhe, Charles; Carlson, Michele; Shade, Dave; Sensinger, Lee McCaffrey] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA.
[Formby, Craig; Tucker, Melanie] Univ Alabama, Tuscaloosa, AL USA.
[Hughes, Gordon] Natl Inst Deafness & Other Commun Disorders, Bethesda, MD USA.
[Conley, George S.; Downey, Naomi] Naval Med Ctr, Portsmouth, VA USA.
[Eades, Cynthia; Haber-Perez, Ada; Harper, Courtney] Travis Air Force Base, David Grant Med Ctr, Travis, CA USA.
[Jylkka, Margaret; Russell, Shoshannah Kantor] Walter Reed Natl Mil Med Ctr, Bethesda, MD USA.
[Sierra-Irizarry, Benigno; Sullivan, Mark] Lackland AFB, Wilford Hall Ambulatory Surg Ctr, San Antonio, TX USA.
RP Scherer, RW (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA.
EM rschere1@jhu.edu
FU NIDCD [U01DC007411, U01DC007422]
FX The TRTT project and the preparation of this manuscript are supported by
the NIDCD: awards U01DC007411 to CF, TRTT study chair, and U01DC007422
to RS, director of the data coordinating center. The sponsor had no role
in the design, data collection, analysis, or writing of the manuscript
or decision to submit the manuscript for publication.
NR 31
TC 1
Z9 1
U1 1
U2 10
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1745-6215
J9 TRIALS
JI Trials
PD OCT 15
PY 2014
VL 15
AR 396
DI 10.1186/1745-6215-15-396
PG 15
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA AT1PP
UT WOS:000344706200001
PM 25319676
ER
PT J
AU Kaur, S
Chang, T
Singh, SP
Lim, L
Mannan, P
Garfield, SH
Pendrak, ML
Soto-Pantoja, DR
Rosenberg, AZ
Jin, S
Roberts, DD
AF Kaur, Sukhbir
Chang, Tiffany
Singh, Satya P.
Lim, Langston
Mannan, Poonam
Garfield, Susan H.
Pendrak, Michael L.
Soto-Pantoja, David R.
Rosenberg, Avi Z.
Jin, Shelly
Roberts, David D.
TI CD47 Signaling Regulates the Immunosuppressive Activity of VEGF in T
Cells
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID ENDOTHELIAL GROWTH-FACTOR; CANCER-CELLS; DENDRITIC CELLS; PROTEIN CD47;
TUMOR-GROWTH; IN-VIVO; C-MYC; THROMBOSPONDIN-1; ACTIVATION; INTEGRIN
AB Thrombospondin-1 (TSP1) inhibits angiogenesis, in part, by interacting with the ubiquitous cell-surface receptor CD47. In endothelial cells, CD47 interacts directly with vascular endothelial growth factor receptor (VEGFR)-2, and TSP1 inhibits VEGFR2 phosphorylation and signaling by disrupting this association. We show that CD47 similarly associates with and regulates VEGFR2 in T cells. TSP1 inhibits phosphorylation of VEGFR2 and its downstream target Src in wild type but not in CD47-deficient human Jurkat and primary murine T cells. VEGFR2 signaling inhibits proliferation and TCR signaling in wild type T cells. However, ligation of CD47 by TSP1 or loss of CD47 expression reverses some inhibitory effects of VEGF on proliferation and T cell activation. We further found that VEGF and VEGFR2 expression are upregulated in CD47-deficient murine CD4(+) and human Jurkat T cells, and the resulting autocrine VEGFR2 signaling enhances proliferation and some TCR responses in the absence of CD47. Thus, CD47 signaling modulates the ability of VEGF to regulate proliferation and TCR signaling, and autocrine production of VEGF by T cells contributes to this regulation. This provides a mechanism to understand the context-dependent effects of TSP1 and VEGF on T cell activation, and reveals an important role for CD47 signaling in regulating T cell production of the major angiogenic factor VEGF.
C1 [Kaur, Sukhbir; Chang, Tiffany; Pendrak, Michael L.; Soto-Pantoja, David R.; Rosenberg, Avi Z.; Jin, Shelly; Roberts, David D.] NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20982 USA.
[Singh, Satya P.] NIAID, Lab Mol Immunol, NIH, Bethesda, MD 20982 USA.
[Lim, Langston; Mannan, Poonam; Garfield, Susan H.] NCI, Expt Carcinogenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Roberts, DD (reprint author), NIH, Bldg 10,Room 2A33,10 Ctr Dr, Bethesda, MD 20892 USA.
EM droberts@helix.nih.gov
RI Roberts, David/A-9699-2008;
OI Roberts, David/0000-0002-2481-2981; Rosenberg, Avi/0000-0003-2356-950X
FU National Institutes of Health Intramural Research Programs of the
National Cancer Institute
FX This work was supported by the National Institutes of Health Intramural
Research Programs of the National Cancer Institute (to D.D.R. and
S.H.G.).
NR 48
TC 12
Z9 12
U1 2
U2 5
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 OCT 15
PY 2014
VL 193
IS 8
BP 3914
EP 3924
DI 10.4049/jimmunol.1303116
PG 11
WC Immunology
SC Immunology
GA AS1ZF
UT WOS:000344078200010
PM 25200950
ER
PT J
AU Rupp, LJ
Brady, BL
Carpenter, AC
De Obaldia, ME
Bhandoola, A
Bosselut, R
Muljo, SA
Bassing, CH
AF Rupp, Levi J.
Brady, Brenna L.
Carpenter, Andrea C.
De Obaldia, Maria Elena
Bhandoola, Avinash
Bosselut, Remy
Muljo, Stefan A.
Bassing, Craig H.
TI The microRNA Biogenesis Machinery Modulates Lineage Commitment during
alpha beta T Cell Development
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID POSITIVE SELECTION; GENE-EXPRESSION; LYMPHOCYTE DEVELOPMENT; DEVELOPING
THYMOCYTES; MEDIATED ACTIVATION; NEGATIVE SELECTION; TRANSGENIC MICE;
CD4 EXPRESSION; REGULATES CD4; DIFFERENTIATION
AB Differentiation of CD4(+) helper and CD8(+) cytotoxic alpha beta T cells from CD4(+)CD8(+) thymocytes involves upregulation of lineage-specifying transcription factors and transcriptional silencing of CD8 or CD4 coreceptors, respectively, in MHC class II or I (MHCII or I)-restricted thymocytes. In this study, we demonstrate that inactivation of the Dicer RNA endonuclease in murine thymocytes impairs initiation of Cd4 and Cd8 silencing, leading to development of positively selected MHCI- and MHCII-restricted mature CD4(+)CD8(+) thymocytes. Expression of the antiapoptotic BCL2 protein or inactivation of the p53 proapoptotic protein rescues these thymocytes from apoptosis, increasing their frequency and permitting accumulation of CD4(+)CD8(+) alpha beta T cells in the periphery. Dicer-deficient MHCI-restricted ab T cells fail to normally silence Cd4 and display impaired induction of the CD8 lineage-specifying transcription factor Runx3, whereas Dicer-deficient MHCII-restricted alpha beta T cells show impaired Cd8 silencing and impaired induction of the CD4 lineage-specifying transcription factor Thpok. Finally, we show that the Drosha RNA endonuclease, which functions upstream of Dicer in microRNA biogenesis, also regulates Cd4 and Cd8 silencing. Our data demonstrate a previously dismissed function for the microRNA biogenesis machinery in regulating expression of lineage-specifying transcription factors and silencing of Cd4 and Cd8 during alpha beta T cell differentiation.
C1 [Rupp, Levi J.; Brady, Brenna L.; Bassing, Craig H.] Childrens Hosp Philadelphia, Ctr Childhood Canc Res, Dept Pathol & Lab Med, Div Canc Pathobiol, Philadelphia, PA 19104 USA.
[Rupp, Levi J.; Brady, Brenna L.; Bassing, Craig H.] Univ Penn, Perelman Sch Med, Abramson Family Canc Res Inst, Philadelphia, PA 19104 USA.
[Rupp, Levi J.; Bassing, Craig H.] Univ Penn, Perelman Sch Med, Cell & Mol Biol Grad Grp, Philadelphia, PA 19104 USA.
[Brady, Brenna L.; Muljo, Stefan A.] NIAID, Integrat Immunobiol Unit, Immunol Lab, NIH, Bethesda, MD 20892 USA.
[Carpenter, Andrea C.; Bosselut, Remy] NCI, Lab Immune Cell Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[De Obaldia, Maria Elena; Bhandoola, Avinash; Bassing, Craig H.] Univ Penn, Perelman Sch Med, Dept Pathol & Lab Med, Immunol Grad Grp, Philadelphia, PA 19104 USA.
RP Bassing, CH (reprint author), Childrens Hosp Philadelphia, 4054 Colket Translat Res Bldg,3501 Civ Ctr Blvd, Philadelphia, PA 19104 USA.
EM bassing@email.chop.edu
RI Muljo, Stefan/F-5671-2015
OI Muljo, Stefan/0000-0003-1013-446X
FU University of Pennsylvania training grants in Computational Genomics
[HG-000046]; Cell and Molecular Biology [GM-07229]; Immunobiology of
Normal and Neoplastic Lymphocytes [CA-009140]; National Institutes of
Health Intramural Research Programs of the Center for Cancer Research -
National Cancer Institute; National Institute of Allergy and Infectious
Diseases; National Institutes of Health [AI059621, CA125195, CA136470];
Leukemia and Lymphoma Society scholar award
FX This work was supported by University of Pennsylvania training grants in
Computational Genomics (HG-000046 to L.J.R.), Cell and Molecular Biology
(GM-07229 to B.L.B. and M.E.D.O.), and Immunobiology of Normal and
Neoplastic Lymphocytes (CA-009140 to M.E.D.O.); the National Institutes
of Health Intramural Research Programs of the Center for Cancer Research
- National Cancer Institute (to A.C.C. and R.B.) and National Institute
of Allergy and Infectious Diseases (to B.L.B. and S.A.M.); National
Institutes of Health Grant AI059621 (to A.B.); a Leukemia and Lymphoma
Society scholar award (to C.H.B.); and National Institutes of Health
Grants CA125195 and CA136470 (to C.H.B.).
NR 49
TC 2
Z9 2
U1 0
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 OCT 15
PY 2014
VL 193
IS 8
BP 4032
EP 4042
DI 10.4049/jimmunol.1401359
PG 11
WC Immunology
SC Immunology
GA AS1ZF
UT WOS:000344078200021
PM 25217159
ER
PT J
AU Maltby, S
Hansbro, NG
Tay, HL
Stewart, J
Plank, M
Donges, B
Rosenberg, HF
Foster, PS
AF Maltby, Steven
Hansbro, Nicole G.
Tay, Hock L.
Stewart, Jessica
Plank, Maximilian
Donges, Bianca
Rosenberg, Helene F.
Foster, Paul S.
TI Production and Differentiation of Myeloid Cells Driven by
Proinflammatory Cytokines in Response to Acute Pneumovirus Infection in
Mice
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID RESPIRATORY SYNCYTIAL VIRUS; HEMATOPOIETIC STEM-CELLS; ESCHERICHIA-COLI
BACTEREMIA; COLONY-STIMULATING FACTOR; INTERFERON-GAMMA;
SUPPRESSOR-CELLS; PROGENITOR CELLS; PNEUMONIA VIRUS; BONE-MARROW;
EARLY-LIFE
AB Respiratory virus infections are often pathogenic, driving severe inflammatory responses. Most research has focused on localized effects of virus infection and inflammation. However, infection can induce broad-reaching, systemic changes that are only beginning to be characterized. In this study, we assessed the impact of acute pneumovirus infection in C57BL/6 mice on bone marrow hematopoiesis. We hypothesized that inflammatory cytokine production in the lung upregulates myeloid cell production in response to infection. We demonstrate a dramatic increase in the percentages of circulating myeloid cells, which is associated with pronounced elevations in inflammatory cytokines in serum (IFN-gamma, IL-6, CCL2), bone (TNF-alpha), and lung tissue (TNF-alpha, IFN-gamma, IL-6, CCL2, CCL3, G-CSF, osteopontin). Increased hematopoietic stem/progenitor cell percentages (Lineage(-)Sca-I(+)c-kit(+)) were also detected in the bone marrow. This increase was accompanied by an increase in the proportions of committed myeloid progenitors, as determined by colony-forming unit assays. However, no functional changes in hematopoietic stem cells occurred, as assessed by competitive bone marrow reconstitution. Systemic administration of neutralizing Abs to either TNF-alpha or IFN-gamma blocked expansion of myeloid progenitors in the bone marrow and also limited virus clearance from the lung. These findings suggest that acute inflammatory cytokines drive production and differentiation of myeloid cells in the bone marrow by inducing differentiation of committed myeloid progenitors. Our findings provide insight into the mechanisms via which innate immune responses regulate myeloid cell progenitor numbers in response to acute respiratory virus infection.
C1 [Maltby, Steven; Hansbro, Nicole G.; Tay, Hock L.; Stewart, Jessica; Plank, Maximilian; Donges, Bianca; Foster, Paul S.] Univ Newcastle, Prior Res Ctr Asthma & Resp Dis, Callaghan, NSW 2308, Australia.
[Maltby, Steven; Hansbro, Nicole G.; Tay, Hock L.; Stewart, Jessica; Plank, Maximilian; Donges, Bianca; Foster, Paul S.] Univ Newcastle, Fac Hlth, Sch Biomed Sci & Pharm, Dept Microbiol & Immunol, Callaghan, NSW 2308, Australia.
[Maltby, Steven; Hansbro, Nicole G.; Tay, Hock L.; Stewart, Jessica; Plank, Maximilian; Donges, Bianca; Foster, Paul S.] Hunter Med Res Inst, New Lambton Hts, NSW 2305, Australia.
[Rosenberg, Helene F.] NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA.
RP Maltby, S (reprint author), Hunter Med Res Inst, Lot 1 Kookaburra Circuit, New Lambton Hts, NSW 2305, Australia.
EM steven.maltby@newcastle.edu.au; paul.foster@newcastle.edu.au
OI Maltby, Steven/0000-0003-1240-5964
FU National Health and Medical Research Council of Australia; National
Institute of Allergy and Infectious Diseases, Division of Intramural
Research; University of Newcastle; Canadian Institutes of Health
Research
FX This work was supported by project grants from the National Health and
Medical Research Council of Australia; the National Institute of Allergy
and Infectious Diseases, Division of Intramural Research; a start-up
grant and a fellowship (to S.M.) from the University of Newcastle; and a
fellowship from the Canadian Institutes of Health Research (to S.M.).
NR 60
TC 4
Z9 5
U1 0
U2 4
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 OCT 15
PY 2014
VL 193
IS 8
BP 4072
EP 4082
DI 10.4049/jimmunol.1400669
PG 11
WC Immunology
SC Immunology
GA AS1ZF
UT WOS:000344078200025
PM 25200951
ER
PT J
AU Gao, KC
Nair, G
Cortese, ICM
Koretsky, A
Reich, DS
AF Gao, Katherine C.
Nair, Govind
Cortese, Irene C. M.
Koretsky, Alan
Reich, Daniel S.
TI Sub-millimeter imaging of brain-free water for rapid volume assessment
in atrophic brains
SO NEUROIMAGE
LA English
DT Article
DE Multiple sclerosis; Atrophy; Magnetic resonance imaging; Cerebrospinal
fluid
ID REMITTING MULTIPLE-SCLEROSIS; SPIN-ECHO SEQUENCE; FOLLOW-UP; MATTER
ATROPHY; TRAIN-LENGTH; INNER-EAR; MR; SEGMENTATION; DISABILITY; DISEASE
AB Introduction: Cerebral atrophy occurs in healthy aging, and in disease processes such as multiple sclerosis (MS), it correlates with disability accumulation. Imaging measurements of brain atrophy are commonly based on tissue segmentation, which is susceptible to classification errors and inconsistencies. High-resolution imaging techniques with strong contrast between brain parenchyma and cerebrospinal fluid (CSF) might allow fully automated, rapid, threshold-based determination of the free water in the brain. We hypothesized that total brain-free-water (BFW) volume and BFW volume expressed as a normalized fraction of the intracranial volume ("BFW fraction"), determined from heavily T-2-weighted images, would be useful surrogates for cerebral atrophy and therefore would correlate with clinical measures of disability in MS.
Methods: Whole brains of 83 MS cases and 7 healthy volunteers were imaged with a 4.7-min, heavily T2-weighted sequence on a 3 T MRI scanner, acquiring 650-mu m isotropic voxels. MS cases were clinically assessed on the Expanded Disability Status Scale (EDSS), Scripps Neurological Rating Scale (SNRS), Paced Auditory Serial Addition Test (PASAT), 9-Hole Peg Test (9HPT), Symbol Digit Modalities Test (SDMT), and 25-Foot Timed Walk. Twelve of the MS cases were rescanned within an average of 1.8 months to assess reproducibility. Automated calculations of BFW volume and BFW fraction were correlated with clinical measures of disability upon adjusting for age and sex. Results were compared to data from T-1-based approaches (SIENAX and Lesion-TOADS).
Results and discussion: BFW volume was automatically derived from heavily T-2-weighted images with no need for separate skull stripping. BFW volume and fraction had mean scan-rescan coefficients of variation of 1.5% and 1.9%, respectively, similar to the T-1-based approaches tested here. BFW fraction more strongly correlated with clinical measures than T-1-derived results. Among those clinical measures, modality-specific disability scores, such as SDMT and 9HPT, were more strongly associated with BFW fraction than composite measures, such as EDSS and SNRS.
Conclusion: The BFW method robustly estimates cerebral atrophy in an automated, fast, and reliable manner, and as such may prove a useful addition to imaging protocols for clinical practice and trials. Published by Elsevier Inc.
C1 [Gao, Katherine C.; Nair, Govind; Cortese, Irene C. M.; Koretsky, Alan; Reich, Daniel S.] NINDS, NIH, Bethesda, MD 20892 USA.
RP Nair, G (reprint author), NINDS, NIH, Bldg 10,Rm 5C103,10 Ctr Dr,MSC 1400, Bethesda, MD 20892 USA.
EM govind.bhagavatheeswaran@nih.gov
RI Reich, Daniel/E-5701-2010; Koretsky, Alan/C-7940-2015
OI Reich, Daniel/0000-0002-2628-4334; Koretsky, Alan/0000-0002-8085-4756
FU Intramural Research Program of the National Institute of Neurologic
Disorders and Stroke (NINDS), National Institutes of Health
FX This study was supported by the Intramural Research Program of the
National Institute of Neurologic Disorders and Stroke (NINDS), National
Institutes of Health. We are grateful to the Neuroimmunology Clinic
(especially Joan Ohayon and Kaylan Fenton) for performing neurological
exams on our participants, the National Institute of Mental Health
(NIMH)/NINDS Functional Magnetic Resonance Facility, Tianxia Wu (NINDS),
Colin Shea (NINDS), John Ostuni (NINDS), and Souheil Inati (NIMH).
NR 47
TC 3
Z9 3
U1 1
U2 3
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1053-8119
EI 1095-9572
J9 NEUROIMAGE
JI Neuroimage
PD OCT 15
PY 2014
VL 100
BP 370
EP 378
DI 10.1016/j.neuroimage.2014.06.014
PG 9
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA AS4HU
UT WOS:000344235800032
PM 24945671
ER
PT J
AU Kitahara, CM
Gamborg, M
Rajaraman, P
Sorensen, TIA
Baker, JL
AF Kitahara, Cari M.
Gamborg, Michael
Rajaraman, Preetha
Sorensen, Thorkild I. A.
Baker, Jennifer L.
TI A Prospective Study of Height and Body Mass Index in Childhood, Birth
Weight, and Risk of Adult Glioma Over 40 Years of Follow-up
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Article
DE adolescence; birth weight; body mass index; brain neoplasms; childhood;
glioma; height; prospective studies
ID LARGE PROSPECTIVE COHORT; NERVOUS-SYSTEM TUMORS; BRAIN-TUMORS;
CANCER-RISK; GROWTH; METAANALYSIS; ASSOCIATION; MENINGIOMA; HISTORY;
WOMEN
AB Greater attained height and greater body mass index (BMI; weight (kg)/height (m)(2)) in young adulthood have been associated with glioma risk, but few studies have investigated the association with body size at birth or during childhood, when the brain undergoes rapid cell growth and differentiation. The Copenhagen School Health Records Register includes data on 320,425 Danish schoolchildren born between 1930 and 1989, with height and weight measurements from ages 7-13 years and parentally recorded birth weights. We prospectively evaluated associations between childhood height and BMI, birth weight, and adult glioma risk. During follow-up (1968-2010), 355 men and 253 women aged >= 18 years were diagnosed with glioma. In boys, height at each age between 7 and 13 years was positively associated with glioma risk; hazard ratios per standard-deviation score at ages 7 (approximately 5.1 cm) and 13 (approximately 7.6 cm) years were 1.17 (95% confidence interval (CI): 1.05, 1.30) and 1.21 (95% CI: 1.09, 1.35), respectively. No associations were observed for childhood height in girls or for BMI. Birth weight was positively associated with risk (per 0.5 kg: hazard ratio = 1.13, 95% CI: 1.04, 1.24). These results suggest that exposures associated with higher birth weight and, in boys, greater height during childhood may contribute to the etiology of adult glioma.
C1 [Kitahara, Cari M.; Rajaraman, Preetha] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Gamborg, Michael; Sorensen, Thorkild I. A.; Baker, Jennifer L.] Bispebjerg Hosp, Inst Prevent Med, DK-2400 Copenhagen, Denmark.
[Gamborg, Michael; Sorensen, Thorkild I. A.; Baker, Jennifer L.] Frederiksberg Univ Hosp, Inst Prevent Med, Copenhagen, Denmark.
[Sorensen, Thorkild I. A.; Baker, Jennifer L.] Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn Ctr Basic Metab Res, Copenhagen, Denmark.
RP Baker, JL (reprint author), Bispebjerg Hosp, Inst Prevent Med, Nordre Fasanvej 57, Frederiksberg, Denmark.
EM jennifer.lyn.baker@regionh.dk
RI Baker, Jennifer/F-1917-2010; Kitahara, Cari/R-8267-2016
OI Baker, Jennifer/0000-0002-9649-6615;
FU National Cancer Institute, US National Institutes of Health; European
Research Council (ERC) under the European Union [281418]
FX This research was supported in part by the Intramural Research Program
of the National Cancer Institute, US National Institutes of Health, and
by funding from the European Research Council (ERC) under the European
Union's Seventh Framework Programme (2007-2013) (ERC Grant Agreement
281418 awarded to J.L.B.).
NR 55
TC 5
Z9 5
U1 0
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 OCT 15
PY 2014
VL 180
IS 8
BP 821
EP 829
DI 10.1093/aje/kwu203
PG 9
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA AR7KX
UT WOS:000343759500008
PM 25205831
ER
PT J
AU Zelner, JL
Murray, MB
Becerra, MC
Galea, J
Lecca, L
Calderon, R
Yataco, R
Contreras, C
Zhang, ZB
Grenfell, BT
Cohen, T
AF Zelner, Jonathan L.
Murray, Megan B.
Becerra, Mercedes C.
Galea, Jerome
Lecca, Leonid
Calderon, Roger
Yataco, Rosa
Contreras, Carmen
Zhang, Zibiao
Grenfell, Bryan T.
Cohen, Ted
TI Age-Specific Risks of Tuberculosis Infection From Household and
Community Exposures and Opportunities for Interventions in a High-Burden
Setting
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Article
DE household transmission; preventive therapy; tuberculosis
ID TRANSMISSION; METAANALYSIS; CONTACTS; MODEL
AB We analyzed data from a large population-based prospective cohort study of household contacts of tuberculosis patients in Lima, Peru, to estimate the importance of within-household transmission relative to community-based transmission. We identified all adults (older than 15 years of age) who had incident pulmonary tuberculosis diagnosed at any of 106 public health centers in Lima from September 2009 to August 2012. A total of 14,041 household contacts of 3,446 index patients were assessed for tuberculosis infection and disease. We compared the prevalence of latent tuberculosis infection (LTBI) among persons who had received the Bacillus Calmette-Guerin vaccine in households with and without a microbiologically confirmed index case to estimate the age-specific risk of infection and excess risk of LTBI from household and community exposures. We found that the risk of infection from household and community sources increased from birth until 20 years of age. However, a large proportion of infections among child and young-adult household contacts could have been the result of household exposure. Excess infection risk associated with household exposure accounted for 58% (95% confidence interval: 47, 66) of LTBI prevalence among exposed children younger than 1 year of age, 48% (95% confidence interval: 39, 57) among 10-year-old children, and 44% (95% confidence interval: 34, 51) among 15-year-old adolescents. These findings suggest that expanded access to preventive therapy for older children and young-adult household contacts of known tuberculosis cases may be beneficial.
C1 [Zelner, Jonathan L.; Grenfell, Bryan T.] Princeton Univ, Dept Ecol & Evolutionary Biol, Princeton, NJ 08544 USA.
[Zelner, Jonathan L.; Grenfell, Bryan T.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Murray, Megan B.; Becerra, Mercedes C.] Harvard Univ, Sch Med, Dept Global Hlth & Social Med, Boston, MA USA.
[Murray, Megan B.; Cohen, Ted] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Galea, Jerome; Lecca, Leonid; Calderon, Roger; Yataco, Rosa; Contreras, Carmen] Partners Hlth, Boston, MA USA.
[Galea, Jerome; Lecca, Leonid; Calderon, Roger; Yataco, Rosa; Contreras, Carmen] Socios Salud, Lima, Peru.
[Zhang, Zibiao; Cohen, Ted] Brigham & Womens Hosp, Div Global Hlth Equ, Boston, MA 02115 USA.
RP Zelner, JL (reprint author), Princeton Univ, Dept Ecol & Evolutionary Biol, 106A Guyot Hall, Princeton, NJ 08544 USA.
EM jzelner@princeton.edu
FU Research and Policy for Infectious Disease Dynamics program of the
Science and Technology Directorate, Department of Homeland Security;
Fogarty International Center, National Institutes of Health; Bill and
Melinda Gates Foundation; National Institutes of Health [U19 A1076217]
FX J.L.Z. and B.T.G. were supported by the Research and Policy for
Infectious Disease Dynamics program of the Science and Technology
Directorate, Department of Homeland Security and the Fogarty
International Center, National Institutes of Health. B.T.G. was funded
by the Bill and Melinda Gates Foundation. M.B.M., M.C.B., J.G., L.L.,
R.C., R.Y., C.C., Z.Z., and T.C. were funded by the National Institutes
of Health (grant U19 A1076217).
NR 33
TC 6
Z9 6
U1 1
U2 8
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 OCT 15
PY 2014
VL 180
IS 8
BP 853
EP 861
DI 10.1093/aje/kwu192
PG 9
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA AR7KX
UT WOS:000343759500012
PM 25190676
ER
PT J
AU Hartman, RL
Huestis, MA
AF Hartman, Rebecca L.
Huestis, Marilyn A.
TI RE: "TRENDS IN ALCOHOL AND OTHER DRUGS DETECTED IN FATALLY INJURED
DRIVERS IN THE UNITED STATES, 1999-2010"
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Letter
ID CANNABIS; BLOOD
C1 [Hartman, Rebecca L.; Huestis, Marilyn A.] NIDA, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
RP Hartman, RL (reprint author), NIDA, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
EM mhuestis@intra.nida.nih.gov
FU Intramural NIH HHS
NR 8
TC 3
Z9 3
U1 0
U2 2
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0002-9262
EI 1476-6256
J9 AM J EPIDEMIOL
JI Am. J. Epidemiol.
PD OCT 15
PY 2014
VL 180
IS 8
BP 862
EP 863
DI 10.1093/aje/kwu251
PG 2
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA AR7KX
UT WOS:000343759500013
PM 25245042
ER
PT J
AU Wang, B
Wang, Q
Wang, Z
Jiang, J
Yu, SC
Ping, YF
Yang, J
Xu, SL
Ye, XZ
Xu, C
Yang, L
Qian, C
Wang, JM
Cui, YH
Zhang, X
Bian, XW
AF Wang, Bin
Wang, Qiang
Wang, Zhe
Jiang, Jun
Yu, Shi-Cang
Ping, Yi-Fang
Yang, Jing
Xu, Sen-Lin
Ye, Xian-Zong
Xu, Chuan
Yang, Lang
Qian, Cheng
Wang, Ji Ming
Cui, You-Hong
Zhang, Xia
Bian, Xiu-Wu
TI Metastatic Consequences of Immune Escape from NK Cell Cytotoxicity by
Human Breast Cancer Stem Cells
SO CANCER RESEARCH
LA English
DT Article
ID NATURAL-KILLER-CELLS; TUMOR-CELLS; MESENCHYMAL TRANSITION; INITIATING
CELLS; IN-VITRO; RECOGNITION; EXPRESSION; RESPONSES; MICRORNA; RECEPTOR
AB Breast cancer stem-like cells (BCSC) are crucial for metastasis but the underlying mechanisms remain elusive. Here, we report that tumor-infiltrating natural killer (NK) cells failed to limit metastasis and were not associated with improved therapeutic outcome of BCSC-rich breast cancer. Primary BCSCs were resistant to cytotoxicity mediated by autologous/allogeneic NK cells due to reduced expression of MICA and MICB, two ligands for the stimulatory NK cell receptor NKG2D. Furthermore, the downregulation of MICA/MICB in BCSCs was mediated by aberrantly expressed oncogenic miR20a, which promoted the resistance of BCSC to NK cell cytotoxicity and resultant lung metastasis. The breast cancer cell differentiation-inducing agent, all-trans retinoic acid, restored the miR20a-MICA/MICB axis and sensitized BCSC to NK cell-mediated killing, thereby reducing immune escape-associated BCSC metastasis. Together, our findings reveal a novel mechanism for immune escape of human BCSC and identify the miR20a-MICA/MICB signaling axis as a therapeutic target to limit metastatic breast cancer. (C) 2014 AACR.
C1 [Wang, Bin; Wang, Qiang; Wang, Zhe; Yu, Shi-Cang; Ping, Yi-Fang; Yang, Jing; Xu, Sen-Lin; Ye, Xian-Zong; Xu, Chuan; Yang, Lang; Qian, Cheng; Cui, You-Hong; Zhang, Xia; Bian, Xiu-Wu] Third Mil Med Univ, Southwest Hosp, Inst Pathol, Chongqing 400038, Peoples R China.
[Wang, Bin; Wang, Qiang; Wang, Zhe; Yu, Shi-Cang; Ping, Yi-Fang; Yang, Jing; Xu, Sen-Lin; Ye, Xian-Zong; Xu, Chuan; Yang, Lang; Qian, Cheng; Cui, You-Hong; Zhang, Xia; Bian, Xiu-Wu] Third Mil Med Univ, Southwest Hosp, Southwest Canc Ctr, Chongqing 400038, Peoples R China.
[Wang, Bin; Wang, Qiang; Wang, Zhe; Yu, Shi-Cang; Ping, Yi-Fang; Yang, Jing; Xu, Sen-Lin; Ye, Xian-Zong; Xu, Chuan; Yang, Lang; Qian, Cheng; Cui, You-Hong; Zhang, Xia; Bian, Xiu-Wu] Minist Educ China, Key Lab Tumor Immunopathol, Chongqing, Peoples R China.
[Jiang, Jun] Third Mil Med Univ, Southwest Hosp, Breast Surg Ctr, Chongqing 400038, Peoples R China.
[Wang, Ji Ming] NCI, Lab Mol Immunoregulat, Canc & Inflammat Program, Ctr Canc Res, Frederick, MD 21701 USA.
RP Bian, XW (reprint author), Third Mil Med Univ, Southwest Hosp, Inst Pathol, Gaotanyan 30, Chongqing 400038, Peoples R China.
EM bianxiuwu@263.net
RI Zhang, Xia/B-8152-2008; Bian, Xiu-wu/D-4736-2017
OI Zhang, Xia/0000-0002-9040-1486; Bian, Xiu-wu/0000-0003-4383-0197
FU National Basic Research Program of China (973 Program) [2010CB529403];
National Natural Science Foundation of China [81071771, 30930103,
30725035, 81101631, 81101606]; National Science and Technology Major
Program [2011ZX09102-010-02]; Natural Science Foundation Project of CQ
CSTC [CSTC2012JJA10124]; Intramural Research Program of the National
Cancer Institute, NIH
FX This work was supported by grants from the National Basic Research
Program of China (973 Program, no. 2010CB529403; X.-W. Bian), the
National Natural Science Foundation of China [nos. 81071771, 30930103,
and 30725035 (X-W. Bian); 81101631 (B. Wang); and 81101606 (Z. Wang)],
the National Science and Technology Major Program (no.
2011ZX09102-010-02; X.-W. Bian), and the Natural Science Foundation
Project of CQ CSTC (no. CSTC2012JJA10124; B. Wang). J.-M. Wang was
supported by the Intramural Research Program of the National Cancer
Institute, NIH.
NR 48
TC 25
Z9 26
U1 1
U2 9
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD OCT 15
PY 2014
VL 74
IS 20
BP 5746
EP 5757
DI 10.1158/0008-5472.CAN-13-2563
PG 12
WC Oncology
SC Oncology
GA AR9CK
UT WOS:000343868800007
PM 25164008
ER
PT J
AU Fu, YP
Kohaar, I
Moore, LE
Lenz, P
Figueroa, JD
Tang, W
Porter-Gill, P
Chatterjee, N
Scott-Johnson, A
Garcia-Closas, M
Muchmore, B
Baris, D
Paquin, A
Ylaya, K
Schwenn, M
Apolo, AB
Karagas, MR
Tarway, M
Johnson, A
Mumy, A
Schned, A
Guedez, L
Jones, MA
Kida, M
Hosain, GMM
Malats, N
Kogevinas, M
Tardon, A
Serra, C
Carrato, A
Garcia-Closas, R
Lloreta, J
Wu, XF
Purdue, M
Andriole, GL
Grubb, RL
Black, A
Landi, MT
Caporaso, NE
Vineis, P
Siddiq, A
Bueno-de-Mesquita, HB
Trichopoulos, D
Ljungberg, B
Severi, G
Weiderpass, E
Krogh, V
Dorronsoro, M
Travis, RC
Tjonneland, A
Brennan, P
Chang-Claude, J
Riboli, E
Prescott, J
Chen, C
De Vivo, I
Govannucci, E
Hunter, D
Kraft, P
Lindstrom, S
Gapstur, SM
Jacobs, EJ
Diver, WR
Albanes, D
Weinstein, SJ
Virtamo, J
Kooperberg, C
Hohensee, C
Rodabough, RJ
Cortessis, VK
Conti, DV
Gago-Dominguez, M
Stern, MC
Pike, MC
Van Den Berg, D
Yuan, JM
Haiman, CA
Cussenot, O
Cancel-Tassin, G
Roupret, M
Comperat, E
Porru, S
Carta, A
Pavanello, S
Arici, C
Mastrangelo, G
Grossman, HB
Wang, ZM
Deng, X
Chung, CC
Hutchinson, A
Burdette, L
Wheeler, W
Fraumeni, JF
Chanock, SJ
Hewitt, SM
Silverman, DT
Rothman, N
Prokunina-Olsson, L
AF Fu, Yi-Ping
Kohaar, Indu
Moore, Lee E.
Lenz, Petra
Figueroa, Jonine D.
Tang, Wei
Porter-Gill, Patricia
Chatterjee, Nilanjan
Scott-Johnson, Alexandra
Garcia-Closas, Montserrat
Muchmore, Brian
Baris, Dalsu
Paquin, Ashley
Ylaya, Kris
Schwenn, Molly
Apolo, Andrea B.
Karagas, Margaret R.
Tarway, McAnthony
Johnson, Alison
Mumy, Adam
Schned, Alan
Guedez, Liliana
Jones, Michael A.
Kida, Masatoshi
Hosain, G. M. Monawar
Malats, Nuria
Kogevinas, Manolis
Tardon, Adonina
Serra, Consol
Carrato, Alfredo
Garcia-Closas, Reina
Lloreta, Josep
Wu, Xifeng
Purdue, Mark
Andriole, Gerald L., Jr.
Grubb, Robert L., III
Black, Amanda
Landi, Maria T.
Caporaso, Neil E.
Vineis, Paolo
Siddiq, Afshan
Bueno-de-Mesquita, H. Bas
Trichopoulos, Dimitrios
Ljungberg, Boerje
Severi, Gianluca
Weiderpass, Elisabete
Krogh, Vittorio
Dorronsoro, Miren
Travis, Ruth C.
Tjonneland, Anne
Brennan, Paul
Chang-Claude, Jenny
Riboli, Elio
Prescott, Jennifer
Chen, Constance
De Vivo, Immaculata
Govannucci, Edward
Hunter, David
Kraft, Peter
Lindstrom, Sara
Gapstur, Susan M.
Jacobs, Eric J.
Diver, W. Ryan
Albanes, Demetrius
Weinstein, Stephanie J.
Virtamo, Jarmo
Kooperberg, Charles
Hohensee, Chancellor
Rodabough, Rebecca J.
Cortessis, Victoria K.
Conti, David V.
Gago-Dominguez, Manuela
Stern, Mariana C.
Pike, Malcolm C.
Van Den Berg, David
Yuan, Jian-Min
Haiman, Christopher A.
Cussenot, Olivier
Cancel-Tassin, Geraldine
Roupret, Morgan
Comperat, Eva
Porru, Stefano
Carta, Angela
Pavanello, Sofia
Arici, Cecilia
Mastrangelo, Giuseppe
Grossman, H. Barton
Wang, Zhaoming
Deng, Xiang
Chung, Charles C.
Hutchinson, Amy
Burdette, Laurie
Wheeler, William
Fraumeni, Joseph, Jr.
Chanock, Stephen J.
Hewitt, Stephen M.
Silverman, Debra T.
Rothman, Nathaniel
Prokunina-Olsson, Ludmila
TI The 19q12 Bladder Cancer GWAS Signal: Association with Cyclin E Function
and Aggressive Disease
SO CANCER RESEARCH
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; CONFERS SUSCEPTIBILITY; GENETIC-VARIATION;
OVARIAN-CANCER; VARIANT; RISK; AMPLIFICATION; EXPRESSION; MUTATIONS;
COMPLEXES
AB A genome-wide association study (GWAS) of bladder cancer identified a genetic marker rs8102137 within the 19q12 region as a novel susceptibility variant. This marker is located upstream of the CCNE1 gene, which encodes cyclin E, a cell-cycle protein. We performed genetic fine-mapping analysis of the CCNE1 region using data from two bladder cancer GWAS (5,942 cases and 10,857 controls). We found that the original GWAS marker rs8102137 represents a group of 47 linked SNPs (with r(2) >= 0.7) associated with increased bladder cancer risk. From this group, we selected a functional promoter variant rs7257330, which showed strong allele-specific binding of nuclear proteins in several cell lines. In both GWASs, rs7257330 was associated only with aggressive bladder cancer, with a combined per-allele OR = 1.18 [95% confidence interval (CI), 1.09-1.27, P = 4.67 x 10(-5)] versus OR = 1.01 (95% CI, 0.93-1.10, P = 0.79) for nonaggressive disease, with P = 0.0015 for case-only analysis. Cyclin E protein expression analyzed in 265 bladder tumors was increased in aggressive tumors (P = 0.013) and, independently, with each rs7257330-A risk allele (P-trend = 0.024). Overexpression of recombinant cyclin E in cell lines caused significant acceleration of cell cycle. In conclusion, we defined the 19q12 signal as the first GWAS signal specific for aggressive bladder cancer. Molecular mechanisms of this genetic association may be related to cyclin E overexpression and alteration of cell cycle in carriers of CCNE1 risk variants. In combination with established bladder cancer risk factors and other somatic and germline genetic markers, the CCNE1 variants could be useful for inclusion into bladder cancer risk prediction models. (C) 2014 AACR.
C1 [Fu, Yi-Ping; Kohaar, Indu; Tang, Wei; Porter-Gill, Patricia; Scott-Johnson, Alexandra; Muchmore, Brian; Paquin, Ashley; Tarway, McAnthony; Mumy, Adam; Prokunina-Olsson, Ludmila] NCI, Div Canc Epidemiol & Genet, Lab Translat Gen, NIH, Bethesda, MD 20892 USA.
[Moore, Lee E.; Figueroa, Jonine D.; Chatterjee, Nilanjan; Baris, Dalsu; Purdue, Mark; Black, Amanda; Landi, Maria T.; Caporaso, Neil E.; Albanes, Demetrius; Weinstein, Stephanie J.; Fraumeni, Joseph, Jr.; Chanock, Stephen J.; Silverman, Debra T.; Rothman, Nathaniel] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Lenz, Petra] Frederick Natl Lab Canc Res, SAIC Frederick Inc, Clin Monitoring Res Program, Clin Res Directorate, Frederick, MD USA.
[Garcia-Closas, Montserrat] Inst Canc Res, Div Genet & Epidemiol, London SW3 6JB, England.
[Ylaya, Kris; Hewitt, Stephen M.] NCI, Ctr Canc Res, Pathol Lab, NIH, Bethesda, MD 20892 USA.
[Schwenn, Molly] Maine Canc Registry, Augusta, ME USA.
[Apolo, Andrea B.] NCI, Ctr Canc Res, Genitourinary Malignancy Branch, Bethesda, MD 20892 USA.
[Karagas, Margaret R.; Schned, Alan] Geisel Sch Med Dartmouth, Lebanon, NH USA.
[Johnson, Alison] Vermont Canc Registry, Burlington, VT USA.
[Guedez, Liliana] NCI, Ctr Canc Res, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA.
[Jones, Michael A.] Maine Med Ctr, Dept Pathol, Portland, ME 04102 USA.
[Jones, Michael A.] Maine Med Ctr, Lab Med, Portland, ME 04102 USA.
[Kida, Masatoshi] Univ Vermont, Coll Med, Dept Pathol, Burlington, VT 05405 USA.
[Hosain, G. M. Monawar] New Hampshire State Canc Registry, Concord, NH USA.
[Malats, Nuria] Spanish Natl Canc Res Ctr, Madrid, Spain.
[Kogevinas, Manolis] Ctr Res Environm Epidemiol CREAL, Barcelona, Spain.
[Kogevinas, Manolis] Hosp Mar Med Res Inst IMIM, Barcelona, Spain.
[Kogevinas, Manolis] Natl Sch Publ Hlth, Athens, Greece.
[Kogevinas, Manolis; Tardon, Adonina; Serra, Consol] CIBER Epidemiol & Salud Publ CIBERESP, Barcelona, Spain.
[Tardon, Adonina] Univ Oviedo, Univ Inst Oncol, Oviedo, Spain.
[Serra, Consol] Univ Pompeu Fabra, Barcelona, Spain.
[Carrato, Alfredo] Hosp Ramon & Cajal, E-28034 Madrid, Spain.
[Garcia-Closas, Reina] Hosp Univ Canarias, Unidad Invest, San Cristobal la Laguna, Spain.
[Lloreta, Josep] Univ Pompeu Fabra, Hosp Mar IMIM, Barcelona, Spain.
[Wu, Xifeng] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA.
[Andriole, Gerald L., Jr.; Grubb, Robert L., III] Washington Univ, Sch Med, Div Urol Surg, St Louis, MO 63110 USA.
[Vineis, Paolo; Siddiq, Afshan; Riboli, Elio] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, London, England.
[Vineis, Paolo; Severi, Gianluca] Human Genet Fdn HuGeF, Turin, Italy.
[Bueno-de-Mesquita, H. Bas] Natl Inst Publ Hlth & Environm RIVM, NL-3720 BA Bilthoven, Netherlands.
[Bueno-de-Mesquita, H. Bas] Univ Med Ctr, Dept Gastroenterol & Hepatol, Utrecht, Netherlands.
[Bueno-de-Mesquita, H. Bas] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England.
[Bueno-de-Mesquita, H. Bas] Univ Malaya, Fac Med, Dept Social & Prevent Med, Kuala Lumpur, Malaysia.
[Trichopoulos, Dimitrios] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Trichopoulos, Dimitrios] Acad Athens, Bureau Epidemiol Res, Athens, Greece.
[Trichopoulos, Dimitrios] Hellen Hlth Fdn, Athens, Greece.
[Ljungberg, Boerje] Umea Univ, Dept Surg & Perioperat Sci Urol & Androl, Umea, Sweden.
[Severi, Gianluca] Cancer Epidemiol Ctr, Canc Council Victoria, Melbourne, Australia.
[Severi, Gianluca] Univ Melbourne, Ctr Epidemiol & Biostat, Melbourne, Vic 3010, Australia.
[Weiderpass, Elisabete] Univ Tromso, Arctic Univ Norway, Fac Hlth Sci, Dept Community Med, Tromso, Norway.
[Weiderpass, Elisabete] Canc Registry Norway, Dept Res, Oslo, Norway.
[Weiderpass, Elisabete] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
[Weiderpass, Elisabete] Samfundet Folkhlsan, Helsinki, Finland.
[Krogh, Vittorio] Ist Nazl Tumori, Fdn IRCCS, I-20133 Milan, Italy.
[Dorronsoro, Miren] Basque Reg Hlth Dept & Ciberesp Biodonostia, Publ Hlth Div Gipuzkoa, San Sebastian, Spain.
[Travis, Ruth C.] Univ Oxford, Canc Epidemiol Unit, Oxford, England.
[Tjonneland, Anne] Danish Canc Soc Res Ctr, Copenhagen, Denmark.
[Brennan, Paul] Int Agcy Res Canc, Lyon, France.
[Chang-Claude, Jenny] German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany.
[Prescott, Jennifer; De Vivo, Immaculata] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA.
[Prescott, Jennifer; De Vivo, Immaculata] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Prescott, Jennifer; Chen, Constance; De Vivo, Immaculata; Hunter, David; Kraft, Peter; Lindstrom, Sara] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Program Genet Epidemiol & Stat Genet, Boston, MA 02115 USA.
[Govannucci, Edward] Harvard Univ, Sch Publ Hlth, Dept Nutr & Epidemiol, Boston, MA 02115 USA.
[Gapstur, Susan M.; Jacobs, Eric J.; Diver, W. Ryan] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA.
[Virtamo, Jarmo] Natl Inst Hlth & Welf, Helsinki, Finland.
[Kooperberg, Charles; Hohensee, Chancellor; Rodabough, Rebecca J.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA.
[Cortessis, Victoria K.] Univ So Calif, Norris Comprehens Canc Ctr, Keck Sch Med USC, Dept Obstet & Gynecol, Los Angeles, CA USA.
[Cortessis, Victoria K.; Conti, David V.; Stern, Mariana C.; Van Den Berg, David; Haiman, Christopher A.] Univ So Calif, Norris Comprehens Canc Ctr, Keck Sch Med USC, Dept Prevent Med, Los Angeles, CA USA.
[Gago-Dominguez, Manuela] Univ Santiago, Complejo Hosp, Galician Fdn Genom Med, Genom Med Grp,SERGAS,IDIS, Santiago De Compostela, Spain.
[Pike, Malcolm C.] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA.
[Yuan, Jian-Min] Univ Pittsburgh, Pittsburgh Canc Inst, Pittsburgh, PA USA.
[Cussenot, Olivier] Hop Tenon, AP HP, Dept Urol, GHU Est, F-75970 Paris, France.
[Cussenot, Olivier; Cancel-Tassin, Geraldine; Roupret, Morgan; Comperat, Eva] Ctr Rech Les Pathol Prostat, Paris, France.
[Cussenot, Olivier; Cancel-Tassin, Geraldine; Roupret, Morgan; Comperat, Eva] Univ Paris 06, ONCOTYPE URO, UPMC, Paris, France.
[Roupret, Morgan; Comperat, Eva] Hop La Pitie Salpetriere, AP HP, GHU Est, Dept Urol & Pathol, Paris, France.
[Porru, Stefano; Carta, Angela; Arici, Cecilia] Univ Brescia, Dept Med & Surg Specialties, Brescia, Italy.
[Pavanello, Sofia; Mastrangelo, Giuseppe] Univ Padua, Dept Cardiac Thorac & Vasc Sci, Padua, Italy.
[Grossman, H. Barton] Univ Texas MD Anderson Canc Ctr, Dept Urol, Houston, TX 77030 USA.
[Wang, Zhaoming; Deng, Xiang; Chung, Charles C.; Hutchinson, Amy; Burdette, Laurie] Frederick Natl Lab Canc Res, SAIC Frederick Inc, Canc Genom Res Lab, Frederick, MD USA.
[Wheeler, William] Informat Management Serv Inc, Rockville, MD USA.
RP Prokunina-Olsson, L (reprint author), NCI, Div Canc Epidemiol & Genet, Lab Translat Gen, NIH, 8717 Grovemont Circle, Bethesda, MD 20892 USA.
EM prokuninal@mail.nih.gov
RI Albanes, Demetrius/B-9749-2015; Garcia-Closas, Montserrat /F-3871-2015;
Malats, Nuria/H-7041-2015; Krogh, Vittorio/K-2628-2016; Weiderpass,
Elisabete/M-4029-2016; Kogevinas, Manolis/C-3918-2017;
OI Cancel-Tassin, Geraldine/0000-0002-9583-6382; Garcia-Closas, Montserrat
/0000-0003-1033-2650; Malats, Nuria/0000-0003-2538-3784; Krogh,
Vittorio/0000-0003-0122-8624; Weiderpass, Elisabete/0000-0003-2237-0128;
Prokunina-Olsson, Ludmila/0000-0002-9622-2091; Hewitt,
Stephen/0000-0001-8283-1788; Yuan, Jian-Min/0000-0002-4620-3108
FU intramural research program (IRP) of the NCI/NIH [HHSN261200800001E]
FX The project was funded in whole or in part with federal funds from the
intramural research program (IRP) of the NCI/NIH (contract no.
HHSN261200800001E).
NR 31
TC 8
Z9 8
U1 0
U2 12
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD OCT 15
PY 2014
VL 74
IS 20
BP 5808
EP 5818
DI 10.1158/0008-5472.CAN-14-1531
PG 11
WC Oncology
SC Oncology
GA AR9CK
UT WOS:000343868800012
PM 25320178
ER
PT J
AU Akita, H
Marquardt, JU
Durkin, ME
Kitade, M
Seo, D
Conner, EA
Andersen, JB
Factor, VM
Thorgeirsson, SS
AF Akita, Hirofumi
Marquardt, Jens U.
Durkin, Marian E.
Kitade, Mitsuteru
Seo, Daekwan
Conner, Elizabeth A.
Andersen, Jesper B.
Factor, Valentina M.
Thorgeirsson, Snorri S.
TI MYC Activates Stem-like Cell Potential in Hepatocarcinoma by a
p53-Dependent Mechanism
SO CANCER RESEARCH
LA English
DT Article
ID AGGRESSIVE LIVER-CANCER; C-MYC; EMBRYONIC STEM; MOUSE MODEL; P53;
EXPRESSION; DIFFERENTIATION; APOPTOSIS; PATHWAY; TARGET
AB Activation of c-MYC is an oncogenic hallmark of many cancers, including liver cancer, and is associated with a variety of adverse prognostic characteristics. Despite a causative role during malignant transformation and progression in hepatocarcinogenesis, consequences of c-MYC activation for the biology of hepatic cancer stem cells (CSC) are undefined. Here, distinct levels of c-MYC overexpression were established by using two dose-dependent tetracycline-inducible systems in four hepatoma cell lines with different p53 mutational status. The CSCs were evaluated using side population (SP) approach as well as standard in vitro and in vivo assays. Functional repression of p53 was achieved by lentiviral shRNA transduction. The results show that c-MYC expression levels have a differential impact on liver CSC characteristics. At low levels, c-MYC activation led to increased proliferation and enhanced CSC properties including activation of reprogramming transcription factors and CSC marker expression (e. g., NANOG, OCT4, and EpCAM), expansion of SP, and acceleration of tumor growth upon subcutaneous transplantation into immunocompromised mice. However, when exceeding a threshold level, c-MYC induced a proapoptotic program and loss of CSC potential both in vitro and in vivo. Mechanistically, c-MYC-induced self-renewal capacity of liver cancer cells was exerted in a p53-dependent manner. Low c-MYC activation increased spheroid formation in p53-deficient tumor cells, whereas p53-dependent effects were blunted in the absence of c-MYC overexpression. Together, our results confirm the role of c-MYC as a master regulator during hepatocarcinogenesis and establish a new gatekeeper role for p53 in repressing c-MYC-induced CSC phenotype in liver cancer cells. (C) 2014 AACR.
C1 [Akita, Hirofumi; Marquardt, Jens U.; Durkin, Marian E.; Kitade, Mitsuteru; Seo, Daekwan; Conner, Elizabeth A.; Andersen, Jesper B.; Factor, Valentina M.; Thorgeirsson, Snorri S.] NCI, Lab Expt Carcinogenesis, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Marquardt, Jens U.] Johannes Gutenberg Univ Mainz, Dept Med 1, Mainz, Germany.
[Andersen, Jesper B.] Univ Copenhagen, Biotech Res & Innovat Ctr, Copenhagen, Denmark.
RP Thorgeirsson, SS (reprint author), NCI, Lab Expt Carcinogenesis, Ctr Canc Res, NIH, 37 Convent Dr, Bethesda, MD 20892 USA.
EM snorri_thorgeirsson@nih.gov
OI Andersen , Jesper B/0000-0003-1760-5244
FU Intramural Research Program of the Center for Cancer Research, NCI;
German Research Foundation [MA 4443/2-1]
FX This project was supported by the Intramural Research Program of the
Center for Cancer Research, NCI. J.U. Marquardt is supported by a grant
from the German Research Foundation (MA 4443/2-1).
NR 41
TC 21
Z9 22
U1 1
U2 12
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD OCT 15
PY 2014
VL 74
IS 20
BP 5903
EP 5913
DI 10.1158/0008-5472.CAN-14-0527
PG 11
WC Oncology
SC Oncology
GA AR9CK
UT WOS:000343868800020
PM 25189530
ER
PT J
AU Ming, M
Han, WN
Zhao, BZ
Sundaresan, NR
Deng, CX
Gupta, MP
He, YY
AF Ming, Mei
Han, Weinong
Zhao, Baozhong
Sundaresan, Nagalingam R.
Deng, Chu-Xia
Gupta, Mahesh P.
He, Yu-Ying
TI SIRT6 Promotes COX-2 Expression and Acts as an Oncogene in Skin Cancer
SO CANCER RESEARCH
LA English
DT Article
ID HISTONE DEACETYLASE SIRT6; MESSENGER-RNA STABILITY; DNA-REPAIR;
CYCLOOXYGENASE-2 EXPRESSION; TUMOR-SUPPRESSOR; PROTEIN-KINASE;
XERODERMA-PIGMENTOSUM; GENOMIC INSTABILITY; HUMAN KERATINOCYTES; INDUCED
APOPTOSIS
AB SIRT6 is a SIR2 family member that regulates multiple molecular pathways involved in metabolism, genomic stability, and aging. It has been proposed previously that SIRT6 is a tumor suppressor in cancer. Here, we challenge this concept by presenting evidence that skin-specific deletion of SIRT6 in the mouse inhibits skin tumorigenesis. SIRT6 promoted expression of COX-2 by repressing AMPK signaling, thereby increasing cell proliferation and survival in the skin epidermis. SIRT6 expression in skin keratinocytes was increased by exposure to UVB light through activation of the AKT pathway. Clinically, we found that SIRT6 was upregulated in human skin squamous cell carcinoma. Taken together, our results provide evidence that SIRT6 functions as an oncogene in the epidermis and suggest greater complexity to its role in epithelial carcinogenesis. (C) 2014 AACR.
C1 [Ming, Mei; Han, Weinong; Zhao, Baozhong; He, Yu-Ying] Univ Chicago, Dept Med, Dermatol Sect, Chicago, IL 60637 USA.
[Sundaresan, Nagalingam R.; Gupta, Mahesh P.] Univ Chicago, Dept Surg, Comm Cellular & Mol Physiol, Chicago, IL 60637 USA.
[Sundaresan, Nagalingam R.] Indian Inst Sci, Dept Microbiol & Cell Biol, Div Biol Sci, Bangalore 560012, Karnataka, India.
[Deng, Chu-Xia] NIDDK, US NIH, Bethesda, MD USA.
RP He, YY (reprint author), Univ Chicago, Dept Med, Dermatol Sect, 5841 S Maryland Ave, Chicago, IL 60637 USA.
EM yyhe@medicine.bsd.uchicago.edu
RI deng, chuxia/N-6713-2016
FU NIH/NIEHS [ES016936]; American Cancer Society (ACS) [RSG-13-078-01,
HL117041, HL111455]; University of Chicago Cancer Research Center [P30
CA014599]; CTSA [NIH UL1RR024999]; University of Chicago Friends of
Dermatology Endowment Fund
FX This work was supported by NIH/NIEHS grants ES016936 (Y.-Y. He), the
American Cancer Society (ACS) grant RSG-13-078-01 (Y.-Y. He), HL117041
and HL111455 (M.P. Gupta), the University of Chicago Cancer Research
Center (P30 CA014599), the CTSA (NIH UL1RR024999), and the University of
Chicago Friends of Dermatology Endowment Fund.
NR 58
TC 17
Z9 22
U1 4
U2 16
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD OCT 15
PY 2014
VL 74
IS 20
BP 5925
EP 5933
DI 10.1158/0008-5472.CAN-14-1308
PG 9
WC Oncology
SC Oncology
GA AR9CK
UT WOS:000343868800022
PM 25320180
ER
PT J
AU Bates, SE
AF Bates, Susan E.
TI The Lymphoma Medicine Cabinet
SO CLINICAL CANCER RESEARCH
LA English
DT Editorial Material
C1 Natl Canc Inst, Rockville, MD 20850 USA.
RP Bates, SE (reprint author), Natl Canc Inst, Rockville, MD 20850 USA.
NR 2
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 OCT 15
PY 2014
VL 20
IS 20
BP 5172
EP 5172
DI 10.1158/1078-0432.CCR-14-1257
PG 1
WC Oncology
SC Oncology
GA AR9DW
UT WOS:000343873100004
PM 25320366
ER
PT J
AU Dunleavy, K
Roschewski, M
Wilson, WH
AF Dunleavy, Kieron
Roschewski, Mark
Wilson, Wyndham H.
TI Precision Treatment of Distinct Molecular Subtypes of Diffuse Large
B-cell Lymphoma: Ascribing Treatment Based on the Molecular Phenotype
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID RITUXIMAB PLUS CYCLOPHOSPHAMIDE; NON-HODGKINS-LYMPHOMA; DOSE-ADJUSTED
EPOCH; RANDOMIZED CONTROLLED-TRIAL; 3-WEEKLY CHOP CHEMOTHERAPY;
GRAY-ZONE LYMPHOMA; GENE-EXPRESSION; GERMINAL-CENTER; ELDERLY-PATIENTS;
PHASE-II
AB Although diffuse large B-cell lymphoma (DLBCL), the most common type of non-Hodgkin lymphoma, was once considered to be a single disease, novel insights into its biology have revealed that it is molecularly heterogeneous. Technologies such as gene expression profiling have revealed that DLBCL consists of at least three distinct molecular diseases that have disparate outcomes following standard therapy. These subtypes arise from different stages of B-cell differentiation and are characterized by distinct oncogenic activation mechanisms. This knowledge has led to the investigation of strategies and novel agents that have selective activity within molecular subtypes and sets the stage for an era of precision medicine in DLBCL therapeutics, where therapy can be ascribed based on molecular phenotype. This work offers the chance of improving the curability of DLBCL, particularly in the activated B-cell subtype, where standard approaches are inadequate for a high proportion of patients. (C)2014 AACR.
C1 [Dunleavy, Kieron; Roschewski, Mark; Wilson, Wyndham H.] NCI, Lymphoid Malignancy Branch, Bethesda, MD 20892 USA.
RP Wilson, WH (reprint author), NCI, 10 Ctr Dr, Bethesda, MD 20892 USA.
EM wilsonw@mail.nih.gov
NR 102
TC 14
Z9 16
U1 0
U2 6
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
EI 1557-3265
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD OCT 15
PY 2014
VL 20
IS 20
BP 5182
EP 5193
DI 10.1158/1078-0432.CCR-14-0497
PG 12
WC Oncology
SC Oncology
GA AR9DW
UT WOS:000343873100006
PM 25320368
ER
PT J
AU O'Connor, OA
Bhagat, G
Ganapathi, K
Pedersen, MB
D'Amore, F
Radeski, D
Bates, SE
AF O'Connor, Owen A.
Bhagat, Govind
Ganapathi, Karthik
Pedersen, Martin Bjerregaard
D'Amore, Francesco
Radeski, Dejan
Bates, Susan E.
TI Changing the Paradigms of Treatment in Peripheral T-cell Lymphoma: From
Biology to Clinical Practice
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID HISTONE DEACETYLASE INHIBITOR; NON-HODGKIN-LYMPHOMA; GENE-EXPRESSION
ANALYSIS; HUMAN AML CELLS; PHASE-II TRIAL; ANAPLASTIC LYMPHOMA;
BRENTUXIMAB VEDOTIN; PROGNOSTIC-FACTORS; 1ST-LINE TREATMENT; MULTICENTER
TRIAL
AB Despite enormous advances in our understanding of aggressive lymphomas, it is clear that progress in the peripheral T-cell lymphomas (PTCL) has lagged well behind other B-cell malignancies. Although there are many reasons for this, the one commonly cited notes that the paradigms for diffuse large B-cell lymphoma (DLBCL) were merely applied to all patients with PTCL, the classic "one-size-fits-all" approach. Despite these challenges, progress is being made. Recently, the FDA has approved four drugs for patients with relapsed/refractory PTCL over the past 5 years, and if one counts the recent Japanese approval of the anti-CCR4 monoclonal antibody for patients with adult T-cell leukemia/lymphoma, five drugs have been approved worldwide. These efforts have led to the initiation of no fewer than four randomized clinical studies exploring the integration of these new agents into standard CHOP (cyclophosphamide-Adriamycin-vincristine-prednisone)-based chemotherapy regimens for patients with newly diagnosed PTCL. In addition, a new wave of studies are exploring the merits of novel drug combinations in the disease, an effort to build on the obvious single-agent successes. What has emerged most recently is the recognition that the PTCL may be a disease-characterized by epigenetic dysregulation, which may help explain its sensitivity to histone deacetylase (HDAC) inhibitors, and open the door for even more creative combination approaches. Nonetheless, advances made over a relatively short period of time are changing how we now view these diseases and, hopefully, have poised us to finally improve its prognosis. (C)2014 AACR.
C1 [O'Connor, Owen A.; Radeski, Dejan] Columbia Univ, Med Ctr, New York Presbyterian Hosp, Ctr Lymphoid Malignancies,Dept Med, New York, NY USA.
[Bhagat, Govind; Ganapathi, Karthik] Columbia Univ, Med Ctr, Dept Pathol & Cell Biol, Div Hematopathol, New York, NY USA.
[Pedersen, Martin Bjerregaard; D'Amore, Francesco] Aarhus Univ Hosp, Dept Hematol, DK-8000 Aarhus, Denmark.
[Bates, Susan E.] NCI, Dev Therapeut Branch, Bethesda, MD 20892 USA.
RP O'Connor, OA (reprint author), Columbia Univ, Med Ctr, Ctr Lymphoid Malignancies, Dept Med, 51 West 51st St,Suite 200, New York, NY 10027 USA.
EM owenoconnor@columbia.edu
OI Bhagat, Govind/0000-0001-6250-048X
FU Lymphoma Research Fund of Columbia University Medical Center
FX O.A. O'Connor and D. Radeski were supported by the Lymphoma Research
Fund of Columbia University Medical Center.
NR 108
TC 10
Z9 10
U1 0
U2 3
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 OCT 15
PY 2014
VL 20
IS 20
BP 5240
EP 5254
DI 10.1158/1078-0432.CCR-14-2020
PG 15
WC Oncology
SC Oncology
GA AR9DW
UT WOS:000343873100011
PM 25320373
ER
PT J
AU Cao, XM
Yan, JS
Shu, S
Brzostowski, JA
Jin, T
AF Cao, Xiumei
Yan, Jianshe
Shu, Shi
Brzostowski, Joseph A.
Jin, Tian
TI Arrestins function in cAR1 GPCR-mediated signaling and cAR1
internalization in the development of Dictyostelium discoideum
SO MOLECULAR BIOLOGY OF THE CELL
LA English
DT Article
ID LIGAND-INDUCED PHOSPHORYLATION; HETEROTRIMERIC G-PROTEINS; C-TERMINAL
DOMAIN; BETA-ARRESTIN; LIVING CELLS; CHEMOATTRACTANT RECEPTORS;
ADENYLYL-CYCLASE; LEADING-EDGE; CHEMOTAXIS; CAMP
AB Oscillation of chemical signals is a common biological phenomenon, but its regulation is poorly understood. At the aggregation stage of Dictyostelium discoideum development, the chemoattractant cAMP is synthesized and released at 6-min intervals, directing cell migration. Although the G protein-coupled cAMP receptor cAR1 and ERK2 are both implicated in regulating the oscillation, the signaling circuit remains unknown. Here we report that D. discoideum arrestins regulate the frequency of cAMP oscillation and may link cAR1 signaling to oscillatory ERK2 activity. Cells lacking arrestins (adcB(-)C(-)) display cAMP oscillations during the aggregation stage that are twice as frequent as for wild-type cells. The adcB(-)C(-)cells also have a shorter period of transient ERK2 activity and precociously reactivate ERK2 in response to cAMP stimulation. We show that arrestin domain-containing protein C (AdcC) associates with ERK2 and that activation of cAR1 promotes the transient membrane recruitment of AdcC and interaction with cAR1, indicating that arrestins function in cAR1-controlled periodic ERK2 activation and oscillatory cAMP signaling in the aggregation stage of D. discoideum development. In addition, ligand-induced cAR1 internalization is compromised in adcB(-)C(-) cells, suggesting that arrestins are involved in elimination of high-affinity cAR1 receptors from cell surface after the aggregation stage of multicellular development.
C1 [Cao, Xiumei; Yan, Jianshe] Shanghai Jiao Tong Univ, Sch Med, Shanghai Inst Immunol, Shanghai 200025, Peoples R China.
[Yan, Jianshe; Jin, Tian] NIAID, Chemotaxis Signal Sect, Immunogenet Lab, NIH, Rockville, MD 20852 USA.
[Brzostowski, Joseph A.] NIAID, Lab Immunogenet Imaging Facil, NIH, Rockville, MD 20852 USA.
[Shu, Shi] NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Jin, T (reprint author), NIAID, Chemotaxis Signal Sect, Immunogenet Lab, NIH, Rockville, MD 20852 USA.
EM yanjianshe@sjtu.edu.cn; tjin@niaid.nih.gov
FU Intramural Research Program of the National Institute of Allergy and
Infectious Diseases/National Institutes of Health; National Basic
Research Program of China [2014CB541804]; Shanghai Pujiang Program
[14PJ1407700]
FX This study was supported by the Intramural Research Program of the
National Institute of Allergy and Infectious Diseases/National
Institutes of Health and grants from the National Basic Research Program
of China (2014CB541804) and the Shanghai Pujiang Program (14PJ1407700).
The plasmids pLPBLP, pDEX-NLS-cre, pDV-CYFP-CTAP, pDM326, and
pDXA-MCS-YFP were obtained through the Dicty Stock Center
(http://dictybase.org/). We thank A. Muller-Taubenberger (Ludwig
Maximilians University of Munich, Munich, Germany) for providing the
mRFPmars plasmid. We are appreciative to X. Xiang (Uniformed Services
University of the Health Sciences, Bethesda, MD) and D. Hereld (National
Institute on Alcohol Abuse and Alcoholism, Bethesda, MD) for insightful
discussions and comments. We also thank E. Korn and X. Liu (National
Heart, Lung, and Blood Institute, Bethesda, MD), X. Xu and M. Zhao
(National Institute of Allergy and Infectious Diseases, Bethesda, MD),
and Y. Yuan, H. Liu, and Y. Hou (Shanghai Jiao Tong University School of
Medicine, Shanghai, China) for their generous assistance.
NR 50
TC 3
Z9 3
U1 2
U2 10
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 OCT 15
PY 2014
VL 25
IS 20
BP 3210
EP 3221
DI 10.1091/mbc.E14-03-0834
PG 12
WC Cell Biology
SC Cell Biology
GA AR9GL
UT WOS:000343881000009
PM 25143405
ER
PT J
AU Cegielski, JP
Dalton, T
Yagui, M
Wattanaamornkiet, W
Volchenkov, GV
Via, LE
Van der Walt, M
Tupasi, T
Smith, SE
Odendaal, R
Leimane, V
Kvasnovsky, C
Kuznetsova, T
Kurbatova, E
Kummik, T
Kuksa, L
Kliiman, K
Kiryanova, EV
Kim, H
Kim, CK
Kazennyy, BY
Jou, RW
Huang, WL
Ershova, J
Erokhin, VV
Diem, L
Contreras, C
Cho, SN
Chernousova, LN
Chen, MP
Caoili, JC
Bayona, J
Akksilp, S
AF Cegielski, J. Peter
Dalton, Tracy
Yagui, Martin
Wattanaamornkiet, Wanpen
Volchenkov, Grigory V.
Via, Laura E.
Van der Walt, Martie
Tupasi, Thelma
Smith, Sarah E.
Odendaal, Ronel
Leimane, Vaira
Kvasnovsky, Charlotte
Kuznetsova, Tatiana
Kurbatova, Ekaterina
Kummik, Tiina
Kuksa, Liga
Kliiman, Kai
Kiryanova, Elena V.
Kim, HeeJin
Kim, Chang-ki
Kazennyy, Boris Y.
Jou, Ruwen
Huang, Wei-Lun
Ershova, Julia
Erokhin, Vladislav V.
Diem, Lois
Contreras, Carmen
Cho, Sang Nae
Chernousova, Larisa N.
Chen, Michael P.
Campos Caoili, Janice
Bayona, Jaime
Akksilp, Somsak
CA Global Preserving Effective TB Tre
TI Extensive Drug Resistance Acquired During Treatment of
Multidrug-Resistant Tuberculosis
SO CLINICAL INFECTIOUS DISEASES
LA English
DT Article
DE tuberculosis; multidrug-resistant tuberculosis; extensively
drug-resistant tuberculosis; Green Light Committee
ID PROPENSITY SCORE; HEALTH
AB Background. Increasing access to drugs for the treatment of multidrug-resistant (MDR) tuberculosis is crucial but could lead to increasing resistance to these same drugs. In 2000, the international Green Light Committee (GLC) initiative began to increase access while attempting to prevent acquired resistance.
Methods. To assess the GLC's impact, we followed adults with pulmonary MDR tuberculosis from the start to the end of treatment with monthly sputum cultures, drug susceptibility testing, and genotyping. We compared the frequency and predictors of acquired resistance to second-line drugs (SLDs) in 9 countries that volunteered to participate, 5 countries that met GLC criteria, and 4 countries that did not apply to the GLC.
Results. In total, 832 subjects were enrolled. Of those without baseline resistance to specific SLDs, 68 (8.9%) acquired extensively drug-resistant (XDR) tuberculosis, 79 (11.2%) acquired fluoroquinolone (FQ) resistance, and 56 (7.8%) acquired resistance to second-line injectable drugs (SLIs). The relative risk (95% confidence interval [CI]) of acquired resistance was lower at GLC-approved sites: 0.27 (.16-.47) for XDR tuberculosis, 0.28 (.17-.45) for FQ, and 0.15 (.06-.39) to 0.60 (.34-1.05) for 3 different SLIs. The risk increased as the number of potentially effective drugs decreased. Controlling for baseline drug resistance and differences between sites, the odds ratios (95% CIs) were 0.21 (.07-.62) for acquired XDR tuberculosis and 0.23 (.09-.59) for acquired FQ resistance.
Conclusions. Treatment of MDR tuberculosis involves substantial risk of acquired resistance to SLDs, increasing as baseline drug resistance increases. The risk was significantly lower in programs documented by the GLC to meet specific standards.
C1 [Cegielski, J. Peter; Dalton, Tracy; Smith, Sarah E.; Kvasnovsky, Charlotte; Kurbatova, Ekaterina; Ershova, Julia; Diem, Lois; Chen, Michael P.] Ctr Dis Control & Prevent, Atlanta, GA 30333 USA.
[Yagui, Martin] Natl Inst Hlth, Lima, Peru.
[Wattanaamornkiet, Wanpen; Akksilp, Somsak] Minist Publ Hlth, Dept Dis Control, Bangkok, Thailand.
[Volchenkov, Grigory V.; Kuznetsova, Tatiana] Vladimir Oblast TB Dispensary, Vladimir, Russia.
[Via, Laura E.] NIAID, NIH, Bethesda, MD 20892 USA.
[Van der Walt, Martie; Odendaal, Ronel] MRC, Pretoria, South Africa.
[Tupasi, Thelma; Campos Caoili, Janice] Trop Dis Fdn, Manila, Philippines.
[Leimane, Vaira; Kuksa, Liga] Riga East Univ Hosp Ctr TB & Lung Dis, Riga, Latvia.
[Kummik, Tiina; Kliiman, Kai] Tartu Univ Hosp, Tartu, Estonia.
[Kiryanova, Elena V.; Kazennyy, Boris Y.] Orel Oblast TB Dispensary, Oryol, Russia.
[Kim, HeeJin; Kim, Chang-ki] Korean Inst TB, Seoul, South Korea.
[Jou, Ruwen; Huang, Wei-Lun] Taiwan Ctr Dis Control, Taipei, Taiwan.
[Erokhin, Vladislav V.; Chernousova, Larisa N.] Russian Acad Med Sci, Cent TB Res Inst, Moscow 109801, Russia.
[Contreras, Carmen; Bayona, Jaime] Socios Salud Sucursal, Lima, Peru.
[Cho, Sang Nae] Int TB Res Ctr, Chang Won, South Korea.
[Cho, Sang Nae] Yonsei Univ, Coll Med, Seoul, South Korea.
RP Cegielski, JP (reprint author), Ctr Dis Control & Prevent, 1600 Clifton Rd NE,MS E-10, Atlanta, GA 30333 USA.
EM pcegielski@cdc.gov
FU US Agency for International Development [IAA: OGH09-011:CGH10-1010196];
US CDC, Division of Tuberculosis Elimination [CDC-OGH11-12021]
FX This work was supported by the US Agency for International Development
(IAA: OGH09-011:CGH10-1010196) and the US CDC, Division of Tuberculosis
Elimination (CDC-OGH11-12021).
NR 23
TC 43
Z9 43
U1 1
U2 15
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1058-4838
EI 1537-6591
J9 CLIN INFECT DIS
JI Clin. Infect. Dis.
PD OCT 15
PY 2014
VL 59
IS 8
BP 1049
EP 1063
DI 10.1093/cid/ciu572
PG 15
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA AR2KG
UT WOS:000343413200002
PM 25057101
ER
PT J
AU Takahashi, T
Okiura, A
Saito, K
Kohno, M
AF Takahashi, Toru
Okiura, Aya
Saito, Keita
Kohno, Masahiro
TI Identification of Phenylpropanoids in Fig (Ficus carica L.) Leaves
SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
LA English
DT Article
DE fig; Ficus carica; leaf; polyphenol; furanocoumarin; antioxidant;
radical scavenging activity; caffeoylmalic acid
ID CHLOROGENIC ACID; ANTIOXIDANT ACTIVITY; PHENOLIC-COMPOUNDS; RATS;
SUPEROXIDE; OXYGEN; FLUORESCEIN; METABOLISM; EXTRACTION; HUMANS
AB In this study, the phenylpropanoid composition and antioxidant activity of identified components in fig (Ficus carica L.) leaves were examined. Known polyphenols rutin, isoschaftoside, isoquercetin, and chlorogenic acid were identified. Furthermore, caffeoylmalic acid (CMA) was the most abundant polyphenol and was identified for the first time. CMA exhibited antioxidant activity similar to that of vitamin C or catechin. Psoralen and bergapten were identified as known furanocoumarins, with psoralen being the most abundant. Moreover, psoralic acid glucoside (PAG) was identified for the first time. As a precursor of psoralen, PAG content was equivalent to the psoralen content in moles. Notably, the content of these compounds varied between the five fig varieties, and the furanocoumarin and PAG contents varied more than that of the polyphenols. Further investigations concerning the influence of CMA and PAG on human health are necessary to elucidate functionalities of fig leaves.
C1 [Takahashi, Toru; Okiura, Aya] Toyo Inst Food Technol, Kawanishi, Hyogo 6660026, Japan.
[Saito, Keita] NCI, Radiat Biol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Kohno, Masahiro] Tokyo Inst Technol, Dept Bioengn, Midori Ku, Yokohama, Kanagawa 2268502, Japan.
RP Takahashi, T (reprint author), Toyo Inst Food Technol, 23-2,4 Chome, Kawanishi, Hyogo 6660026, Japan.
EM tooru_takahashi@shokuken.or.jp
OI Takahashi, Toru/0000-0001-7437-6615
NR 51
TC 6
Z9 6
U1 9
U2 35
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0021-8561
EI 1520-5118
J9 J AGR FOOD CHEM
JI J. Agric. Food Chem.
PD OCT 15
PY 2014
VL 62
IS 41
BP 10076
EP 10083
DI 10.1021/jf5025938
PG 8
WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science &
Technology
SC Agriculture; Chemistry; Food Science & Technology
GA AR0QN
UT WOS:000343276500015
PM 25198243
ER
PT J
AU Ryu, KS
Tugarinov, V
Clore, GM
AF Ryu, Kyoung-Seok
Tugarinov, Vitali
Clore, G. Marius
TI Probing the Rate-Limiting Step for Intramolecular Transfer of a
Transcription Factor between Specific Sites on the Same DNA Molecule by
N-15(z)-Exchange NMR Spectroscopy
SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Article
ID EXCHANGE SPECTROSCOPY; COGNATE SITES; FACTORS SOX2; HOMEODOMAIN;
BINDING; PROTEIN; TRANSLOCATION; DIFFUSION; ASSOCIATION; RESOLUTION
AB The kinetics of translocation of the homeodomain transcription factor HoxD9 between specific sites of the same or opposite polarities on the same DNA molecule have been studied by N-15(z)-exchange NMR spectroscopy. We show that exchange occurs by two facilitated diffusion mechanisms: a second-order intermolecular exchange reaction between specific sites located on different DNA molecules without the protein dissociating into free solution that predominates at high concentrations of free DNA, and a first-order intramolecular process involving direct transfer between specific sites located on the same DNA molecule. Control experiments using a mixture of two DNA molecules, each possessing only a single specific site, indicate that transfer between specific sites by full dissociation of HoxD9 into solution followed by reassociation is too slow to measure by z-exchange spectroscopy. Intramolecular transfer with comparable rate constants occurs between sites of the same and opposing polarity, indicating that both rotation-coupled sliding and hopping/flipping (analogous to geminate recombination) occur. The half-life for intramolecular transfer (0.51 s) is many orders of magnitude larger than the calculated transfer time (1100 mu s) by sliding, leading us to conclude that the intramolecular transfer rates measured by z-exchange spectroscopy represent the rate-limiting step for a one-base-pair shift from the specific site to the immediately adjacent nonspecific site. At zero concentration of added salt, the intramolecular transfer rate constants between sites of opposing polarity are smaller than those between sites of the same polarity, suggesting that hopping/flipping may become rate-limiting at very low salt concentrations.
C1 [Ryu, Kyoung-Seok; Tugarinov, Vitali; Clore, G. Marius] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
[Ryu, Kyoung-Seok] Korean Basic Sci Inst, Ochang Eup 363883, Chunbuk Do, South Korea.
RP Clore, GM (reprint author), NIDDK, Chem Phys Lab, NIH, Bldg 2, Bethesda, MD 20892 USA.
EM mariusc@mail.nih.gov
FU Intramural Program of NIDDK, NIH; AIDS-Targeted Antiviral Program of the
Office of the Director, NIH
FX We thank Attila Szabo for useful discussions. This work was supported by
the Intramural Program of NIDDK, NIH, and by the AIDS-Targeted Antiviral
Program of the Office of the Director, NIH (to G.M.C.).
NR 23
TC 2
Z9 2
U1 0
U2 9
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 OCT 15
PY 2014
VL 136
IS 41
BP 14369
EP 14372
DI 10.1021/ja5081585
PG 4
WC Chemistry, Multidisciplinary
SC Chemistry
GA AR0QR
UT WOS:000343276900011
PM 25253516
ER
PT J
AU Robertson, RP
Raymond, RH
Lee, DS
Calle, RA
Ghosh, A
Savage, PJ
Shankar, SS
Vassileva, MT
Weir, GC
Fryburg, DA
AF Robertson, R. Paul
Raymond, Ralph H.
Lee, Douglas S.
Calle, Roberto A.
Ghosh, Atalanta
Savage, Peter J.
Shankar, Sudha S.
Vassileva, Maria T.
Weir, Gordon C.
Fryburg, David A.
CA Fdn NIH Biomarkers Consortium
TI Arginine is preferred to glucagon for stimulation testing of beta-cell
function
SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
LA English
DT Article
DE arginine; glucagon; beta-cell function; insulin secretion
ID C-PEPTIDE RESPONSE; INTENSIVE INSULIN THERAPY; DOSE-RESPONSE;
INTRAVENOUS GLUCAGON; SECRETORY RESERVE; DIABETIC-PATIENTS; GLYCEMIC
CONTROL; IN-VIVO; MASS; GLUCOSE
AB A key aspect of research into the prevention and treatment of type 2 diabetes is the availability of reproducible clinical research methodology to assess beta-cell function. One commonly used method employs nonglycemic secretagogues like arginine (arg) or glucagon (glgn). This study was designed to quantify the insulin response to arg and glgn and determine test repeatability and tolerability. Obese over-night-fasted subjects with normal glucose tolerance were studied on 4 separate days: twice using arg (5 g iv) and twice with glgn (1 mg iv). Pre- and postinfusion samples for plasma glucose, insulin, and C-peptide were acquired. Arg and glgn challenges were repeated in the last 10 min of a 60-min glucose (900 mg/min) infusion. Insulin and C-peptide secretory responses were estimated under baseline fasting glucose conditions (AIRarg and AIRglgn) and hyperglycemic (AIRargMAX AIRglgnMAX) states. Relative repeatability was estimated by intraclass correlation coefficient (ICC). Twenty-three (12 men and 11 women) subjects were studied (age: 42.4 +/- 8.3 yr; BMI: 31.4 +/- 2.8 kg/m(2)). Geometric means (95% CI) for baseline-adjusted values AIRarg and AIRglgn were 84 (75-95) and 102 (90 -115) mu U/ml, respectively. After the glucose infusion, AIRargMAX and AIRglgnMAX were 395 (335-466) and 483 (355-658) mu U/ml, respectively. ICC values were >0.90 for AIRarg andAIRargMAX. Glucagon ICCs were 0.83, 0.34, and 0.36, respectively, although the exclusion of one outlier increased the latter two values (to 0.84 and 0.86). Both glgn and arg induced mild adverse events that were transient. Glucagon, but not arginine, induced moderate adverse events due to nausea. Taken together, arginine is preferred to glucagon for assessment of beta-cell function.
C1 [Robertson, R. Paul] Pacific Northwest Diabet Res Inst, Seattle, WA USA.
[Raymond, Ralph H.] R Squared Solut, Skillman, NJ USA.
[Lee, Douglas S.; Calle, Roberto A.] Pfizer Inc, Groton, CT 06340 USA.
[Ghosh, Atalanta] Janssen Res & Dev, Raritan, NJ USA.
[Savage, Peter J.] NIDDK, NIH, Bethesda, MD 20892 USA.
[Shankar, Sudha S.] Eli Lilly & Co, Indianapolis, IN 46285 USA.
[Vassileva, Maria T.] Fdn Natl Inst Hlth, Bethesda, MD USA.
[Weir, Gordon C.] Joslin Diabet Ctr, Boston, MA 02215 USA.
[Fryburg, David A.] ROI BioPharma Consulting, East Lyme, CT 06333 USA.
RP Fryburg, DA (reprint author), ROI BioPharma Consulting, 14 Alexander Dr, East Lyme, CT 06333 USA.
EM dfryburg@roibiopharma.com
FU NIH (NIDDK); FDA; Bristol-Meyers; Janssen; Eli Lilly and Co.; Merck;
Novartis; Novo Nordisk; Pfizer; Sanofi; Takeda
FX The methodological study described in this report was designed and
implemented under the auspices of the FNIH Biomarkers Consortium. The
Biomarkers Consortium is a public/private partnership that develops,
validates, and qualifies biological markers aimed ultimately at
improving clinical research and patient care. For this study, the
Consortium brought together diabetes experts from leading academic
institutions, the Food and Drug Administration, the NIH, the nonprofit
sector, and the pharmaceutical industry to develop the project. This
project was jointly funded by the NIH (NIDDK) and FDA and the following
pharmaceutical companies: Amylin (now Bristol-Meyers), Janssen, Eli
Lilly and Co., Merck, Novartis, Novo Nordisk, Pfizer, Sanofi, and
Takeda. P800 tubes were generously donated by Becton-Dickinson.
NR 40
TC 6
Z9 7
U1 0
U2 2
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0193-1849
EI 1522-1555
J9 AM J PHYSIOL-ENDOC M
JI Am. J. Physiol.-Endocrinol. Metab.
PD OCT 15
PY 2014
VL 307
IS 8
BP E720
EP E727
DI 10.1152/ajpendo.00149.2014
PG 8
WC Endocrinology & Metabolism; Physiology
SC Endocrinology & Metabolism; Physiology
GA AR0AI
UT WOS:000343223700011
PM 25159323
ER
PT J
AU Leelahavanichkul, A
Souza, ACP
Street, JM
Hsu, V
Tsuji, T
Doi, K
Li, LL
Hu, XZ
Zhou, H
Kumar, P
Schnermann, J
Star, RA
Yuen, PST
AF Leelahavanichkul, Asada
Souza, Ana Carolina P.
Street, Jonathan M.
Hsu, Victor
Tsuji, Takayuki
Doi, Kent
Li, Lingli
Hu, Xuzhen
Zhou, Hua
Kumar, Parag
Schnermann, Juergen
Star, Robert A.
Yuen, Peter S. T.
TI Comparison of serum creatinine and serum cystatin C as biomarkers to
detect sepsis-induced acute kidney injury and to predict mortality in
CD-1 mice
SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
LA English
DT Article
DE bilateral nephrectomy; glomerular filtration rate; survival;
Kaplan-Meier; receiver-operating characteristic curve
ID GLOMERULAR-FILTRATION-RATE; CARDIOPULMONARY BYPASS; CARDIAC-SURGERY;
RENAL-FUNCTION; MARKER; IMPACT; LIMITATIONS
AB Acute kidney injury (AKI) dramatically increases sepsis mortality, but AKI diagnosis is delayed when based on serum creatinine (SCr) changes, due in part, to decreased creatinine production. During experimental sepsis, we compared serum cystatin C (sCysC), SCr, and blood urea nitrogen (BUN) to inulin glomerular filtration rate (iGFR) before or 3-18 h after cecal ligation and puncture (CLP)-induced sepsis in CD-1 mice. sCysC had a faster increase and reached peak levels more rapidly than SCr in both sepsis and bilateral nephrectomy (BiNx) models. sCysC was a better surrogate of iGFR than SCr during sepsis. Combining sCysC with SCr values into a composite biomarker improved correlation with iGFR better than any biomarker alone or any other combination. We determined the renal contribution to sCysC handling with BiNx. sCysC and SCr were lower post-BiNx/CLP than post-BiNx alone, despite increased inflammatory and nonrenal organ damage biomarkers. Sepsis decreased CysC production in nephrectomized mice without changing body weight or CysC space. Sepsis decreased sCysC production and increased nonrenal clearance, similar to effects of sepsis on SCr. sCysC, SCr, and BUN were measured 6 h postsepsis to link AKI with mortality. Mice with above-median sCysC, BUN, or SCr values 6 h postsepsis died earlier than mice with below-median values, corresponding to a substantial AKI association with sepsis mortality in this model. sCysC performs similarly to SCr in classifying mice at risk for early mortality. We conclude that sCysC detects AKI early and better reflects iGFR in CLP-induced sepsis. This study shows that renal biomarkers need to be evaluated in specific contexts.
C1 [Leelahavanichkul, Asada; Souza, Ana Carolina P.; Street, Jonathan M.; Hsu, Victor; Tsuji, Takayuki; Doi, Kent; Hu, Xuzhen; Zhou, Hua; Star, Robert A.; Yuen, Peter S. T.] Natl Inst Diabet & Digest & Kidney Dis, Renal Diagnost & Therapeut Unit, NIH, Bethesda, MD 20892 USA.
[Leelahavanichkul, Asada; Souza, Ana Carolina P.; Street, Jonathan M.; Hsu, Victor; Tsuji, Takayuki; Doi, Kent; Li, Lingli; Hu, Xuzhen; Zhou, Hua; Schnermann, Juergen; Star, Robert A.; Yuen, Peter S. T.] Natl Inst Diabet & Digest & Kidney Dis, Kidney Dis Branch, NIH, Bethesda, MD 20892 USA.
[Kumar, Parag] NIH, Dept Pharm, Ctr Clin, Bethesda, MD 20892 USA.
[Leelahavanichkul, Asada] Chulalongkorn Univ, Fac Med, Dept Microbiol, Bangkok 10330, Thailand.
RP Yuen, PST (reprint author), Natl Inst Diabet & Digest & Kidney Dis, NIH, Bldg 10,Rm 3N108,10 Ctr Dr,MSC 1268, Bethesda, MD 20892 USA.
EM py@nih.gov
RI Yuen, Peter/B-1954-2008
OI Yuen, Peter/0000-0001-9557-3909
FU Intramural Research Program of the National Institutes of Health
(National Institute of Diabetes and Digestive and Kidney Diseases)
FX This research was supported by the Intramural Research Program of the
National Institutes of Health (National Institute of Diabetes and
Digestive and Kidney Diseases).
NR 34
TC 7
Z9 9
U1 0
U2 7
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 1931-857X
EI 1522-1466
J9 AM J PHYSIOL-RENAL
JI Am. J. Physiol.-Renal Physiol.
PD OCT 15
PY 2014
VL 307
IS 8
BP F939
EP F948
DI 10.1152/ajprenal.00025.2013
PG 10
WC Physiology; Urology & Nephrology
SC Physiology; Urology & Nephrology
GA AR0CO
UT WOS:000343233400008
PM 25143457
ER
PT J
AU Young, MT
Sandler, DP
DeRoo, LA
Vedal, S
Kaufman, JD
London, SJ
AF Young, Michael T.
Sandler, Dale P.
DeRoo, Lisa A.
Vedal, Sverre
Kaufman, Joel D.
London, Stephanie J.
TI Ambient Air Pollution Exposure and Incident Adult Asthma in a Nationwide
Cohort of U.S. Women
SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
LA English
DT Article
DE asthma incidence; particulate matter; PM2.5; nitrogen dioxide; NO2
ID ONSET ASTHMA; REPORTED ASTHMA; VEHICLE EXHAUST; HEALTH; CHILDREN;
EXACERBATION; ASSOCIATION; HOME
AB Rationale: Limited prior data suggest an association between traffic-related air pollution and incident asthma in adults. No published studies assess the effect of long-term exposures to particulate matter less than 2.5 mu m in diameter (PM2.5) on adult incident asthma.
Objectives: To estimate the association between ambient air pollution exposures (PM2.5 and nitrogen dioxide, NO2) and development of asthma and incident respiratory symptoms.
Methods: The Sister Study is a U.S. cohort study of risk factors for breast cancer and other health outcomes (n = 50,884) in sisters of women with breast cancer (enrollment, 2003-2009). Annual average (2006) ambient PM2.5 and NO2 concentrations were estimated at participants' addresses, using a national land-use/kriging model incorporating roadway information. Outcomes at follow-up (2008-2012) included incident self-reported wheeze, chronic cough, and doctor-diagnosed asthma in women without baseline symptoms.
Measurements and Main Results: Adjusted analyses included 254 incident cases of asthma, 1,023 of wheeze, and 1,559 of chronic cough. For an interquartile range (IQR) difference (3.6 mu g/m(3)) in estimated PM2.5 exposure, the adjusted odds ratio (aOR) was 1.20 (95% confidence interval [CI] = 0.99-1.46, P = 0.063) for incident asthma and 1.14(95% CI = 1.04-1.26, P = 0.008) for incident wheeze. For NO2, there was evidence for an association with incident wheeze (aOR = 1.08, 95% CI = 1.00-1.17, P = 0.048 per IQR of 5.8 ppb). Neither pollutant was significantly associated with incident cough (PM2.5: aOR = 0.95, 95% CI = 0.88-1.03, P = 0.194; NO2: aOR = 1.00, 95% CI = 0.93-1.07, P = 0.939).
Conclusions: Results suggest that PM2.5 exposure increases the risk of developing asthma and that PM2.5 and NO2 increase the risk of developing wheeze, the cardinal symptom of asthma, in adult women.
C1 [Young, Michael T.; Kaufman, Joel D.] Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA.
[Sandler, Dale P.; DeRoo, Lisa A.; London, Stephanie J.] NIEHS, Dept Hlth & Human Serv, Div Intramural Res, Epidemiol Branch,NIH, Res Triangle Pk, NC 27709 USA.
[Vedal, Sverre; Kaufman, Joel D.] Univ Washington, Sch Publ Hlth, Dept Environm & Occupat Hlth Sci, Seattle, WA 98195 USA.
RP London, SJ (reprint author), NIEHS, POB 12233,MD A3-05, Res Triangle Pk, NC 27709 USA.
EM london2@niehs.nih.gov
RI Kaufman, Joel/B-5761-2008;
OI Kaufman, Joel/0000-0003-4174-9037; Sandler, Dale/0000-0002-6776-0018;
London, Stephanie/0000-0003-4911-5290
FU Biostatistics, Epidemiologic and Bioinformatic Training in Environmental
Health Training Grant [ES015459]; U.S. Department of Health and Human
Services, Health Resources and Services Administration's Maternal and
Child Health Bureau [T76MC00011-21-00]; Intramural Program of the NIH,
National Institute of Environmental Health Sciences [Z01 ES044005,
ES49019]; U.S. Environmental Protection Agency [RD831697, R834796];
[K24 ES013195]
FX Supported by a Biostatistics, Epidemiologic and Bioinformatic Training
in Environmental Health Training Grant (ES015459) and by the U.S.
Department of Health and Human Services, Health Resources and Services
Administration's Maternal and Child Health Bureau (Title V, Social
Security Act) (grant T76MC00011-21-00) (M.T.Y.). Supported in part by
the Intramural Program of the NIH, National Institute of Environmental
Health Sciences (Z01 ES044005 and ES49019). J.D.K. was also supported by
K24 ES013195. Exposure modeling was supported by the U.S. Environmental
Protection Agency (RD831697 and R834796). This article does not
necessarily reflect the views of the Agency, and no official endorsement
should be inferred.
NR 31
TC 32
Z9 32
U1 2
U2 36
PU AMER THORACIC SOC
PI NEW YORK
PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA
SN 1073-449X
EI 1535-4970
J9 AM J RESP CRIT CARE
JI Am. J. Respir. Crit. Care Med.
PD OCT 15
PY 2014
VL 190
IS 8
BP 914
EP 921
DI 10.1164/rccm.201403-0525OC
PG 8
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA AR1XJ
UT WOS:000343377600011
PM 25172226
ER
PT J
AU de Joussineau, C
Sahut-Barnola, I
Tissier, F
Dumontet, T
Drelon, C
Batisse-Lignier, M
Tauveron, I
Pointud, JC
Lefrancois-Martinez, AM
Stratakis, CA
Bertherat, J
Val, P
Martinez, A
AF de Joussineau, Cyrille
Sahut-Barnola, Isabelle
Tissier, Frederique
Dumontet, Typhanie
Drelon, Coralie
Batisse-Lignier, Marie
Tauveron, Igor
Pointud, Jean-Christophe
Lefrancois-Martinez, Anne-Marie
Stratakis, Constantine A.
Bertherat, Jerome
Val, Pierre
Martinez, Antoine
TI mTOR pathway is activated by PKA in adrenocortical cells and
participates in vivo to apoptosis resistance in primary pigmented
nodular adrenocortical disease (PPNAD)
SO HUMAN MOLECULAR GENETICS
LA English
DT Article
ID PROTEIN-KINASE-A; CAMP-DEPENDENT ACTIVATION; REGULATORY SUBUNIT;
ADRENAL-CORTEX; ENDOCRINE OVERACTIVITY; SPOTTY PIGMENTATION; CARNEY
COMPLEX; BAD; PHOSPHORYLATION; MUTATIONS
AB Primary pigmented nodular adrenocortical disease (PPNAD) is associated with inactivating mutations of the PRKAR1A tumor suppressor gene that encodes the regulatory subunit R1 alpha of the cAMP-dependent protein kinase (PKA). In human and mouse adrenocortical cells, these mutations lead to increased PKA activity, which results in increased resistance to apoptosis that contributes to the tumorigenic process. We used in vitro and in vivo models to investigate the possibility of a crosstalk between PKA and mammalian target of rapamycin (mTOR) pathways in adrenocortical cells and its possible involvement in apoptosis resistance. Impact of PKA signaling on activation of the mTOR pathway and apoptosis was measured in a mouse model of PPNAD (AdKO mice), in human and mouse adrenocortical cell lines in response to pharmacological inhibitors and in PPNAD tissues by immunohistochemistry. AdKO mice showed increased mTOR complex 1 (mTORC1) pathway activity. Inhibition of mTORC1 by rapamycin restored sensitivity of adrenocortical cells to apoptosis in Ad KO but not in wild-type mice. In both cell lines and mouse adrenals, rapid phosphorylation of mTORC1 targets including BAD proapoptotic protein was observed in response to PKA activation. Accordingly, BAD hyperphosphorylation, which inhibits its proapoptotic activity, was increased in both AdKO mouse adrenals and human PPNAD tissues. In conclusion, mTORC1 pathway is activated by PKA signaling in human and mouse adrenocortical cells, leading to increased cell survival, which is correlated with BAD hyperphosphorylation. These alterations could be causative of tumor formation.
C1 [de Joussineau, Cyrille; Sahut-Barnola, Isabelle; Dumontet, Typhanie; Drelon, Coralie; Batisse-Lignier, Marie; Tauveron, Igor; Pointud, Jean-Christophe; Lefrancois-Martinez, Anne-Marie; Val, Pierre; Martinez, Antoine] Univ Clermont Ferrand, Clermont Univ, Genet Reprod & Dev GReD, F-63012 Clermont Ferrand 1, France.
[de Joussineau, Cyrille; Sahut-Barnola, Isabelle; Dumontet, Typhanie; Drelon, Coralie; Batisse-Lignier, Marie; Tauveron, Igor; Pointud, Jean-Christophe; Lefrancois-Martinez, Anne-Marie; Val, Pierre; Martinez, Antoine] CNRS, UMR6293, GReD, INSERM,U1103, F-63171 Aubiere, France.
[de Joussineau, Cyrille; Sahut-Barnola, Isabelle; Dumontet, Typhanie; Drelon, Coralie; Batisse-Lignier, Marie; Tauveron, Igor; Pointud, Jean-Christophe; Lefrancois-Martinez, Anne-Marie; Val, Pierre; Martinez, Antoine] INSERM, GReD, U1103, F-63171 Aubiere, France.
[Tissier, Frederique; Bertherat, Jerome] Univ Paris 05, Inst Cochin, CNRS, INSERM,U1016,UMR8104, F-75014 Paris, France.
[Tissier, Frederique; Bertherat, Jerome] Hop Cochin, Dept Endocrinol, F-75014 Paris, France.
[Tissier, Frederique; Bertherat, Jerome] Hop Cochin, AP HP, Reference Ctr Rare Adrenal Dis, Dept Pathol, F-75014 Paris, France.
[Tissier, Frederique] Univ Paris 06, Hop La Pitie Salpetriere, Dept Pathol, F-75013 Paris, France.
[Batisse-Lignier, Marie; Tauveron, Igor] Ctr Hosp Univ Clermont Ferrand, Serv Endocrinol, F-63003 Clermont Ferrand, France.
[Stratakis, Constantine A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Endocrinol & Genet, PDEGEN, NIH, Bethesda, MD 20892 USA.
RP Martinez, A (reprint author), Univ Clermont Ferrand, CNRS, UMR6293, GReD,INSERM,U1103, 24 Ave Landais BP80026, F-63171 Aubiere, France.
EM antoine.martinez@univ-bpclermont.fr
FU Universite Blaise Pascal; Universite d'Auvergne; Centre National de la
Recherche Scientifique; Institut National de la Sante et de la Recherche
Medicale; Agence National de la Recherche [ANR-08-GENOPAT-007]
FX This work was supported by Universite Blaise Pascal, Universite
d'Auvergne, Centre National de la Recherche Scientifique, Institut
National de la Sante et de la Recherche Medicale, Agence National de la
Recherche (grant ANR-08-GENOPAT-007).
NR 36
TC 12
Z9 12
U1 0
U2 7
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0964-6906
EI 1460-2083
J9 HUM MOL GENET
JI Hum. Mol. Genet.
PD OCT 15
PY 2014
VL 23
IS 20
BP 5418
EP 5428
DI 10.1093/hmg/ddu265
PG 11
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA AQ9UO
UT WOS:000343202400010
PM 24865460
ER
PT J
AU Wen, WQ
Zheng, W
Okada, Y
Takeuchi, F
Tabara, Y
Hwang, JY
Dorajoo, R
Li, HX
Tsai, FJ
Yang, XB
He, J
Wu, Y
He, MA
Zhang, Y
Liang, J
Guo, XQ
Sheu, WHH
Delahanty, R
Guo, XY
Kubo, M
Yamamoto, K
Ohkubo, T
Go, MJ
Liu, JJ
Gan, W
Chen, CC
Gao, Y
Li, SX
Lee, NR
Wu, C
Zhou, XY
Song, HD
Yao, J
Lee, IT
Long, JR
Tsunoda, T
Akiyama, K
Takashima, N
Cho, YS
Ong, RTH
Lu, L
Chen, CH
Tan, AH
Rice, TK
Adair, LS
Gui, LX
Allison, M
Lee, WJ
Cai, QY
Isomura, M
Umemura, S
Kim, YJ
Seielstad, M
Hixson, J
Xiang, YB
Isono, M
Kim, BJ
Sim, XL
Lu, W
Nabika, T
Lee, J
Lim, WY
Gao, YT
Takayanagi, R
Kang, DH
Wong, TY
Hsiung, C
Wu, IC
Juang, JMJ
Shi, JJ
Choi, BY
Aung, T
Hu, F
Kim, MK
Lim, WY
Wang, TD
Shin, MH
Lee, J
Ji, BT
Lee, YH
Young, TL
Shin, DH
Chun, BY
Cho, MC
Han, BG
Hwu, CM
Assimes, TL
Absher, D
Yan, XF
Kim, E
Kuo, JZ
Kwon, S
Taylor, KD
Chen, YDI
Rotter, JI
Qi, L
Zhu, DL
Wu, TC
Mohlke, KL
Gu, DF
Mo, ZN
Wu, JY
Lin, X
Miki, T
Tai, ES
Lee, JY
Kato, N
Shu, XO
Tanaka, T
AF Wen, Wanqing
Zheng, Wei
Okada, Yukinori
Takeuchi, Fumihiko
Tabara, Yasuharu
Hwang, Joo-Yeon
Dorajoo, Rajkumar
Li, Huaixing
Tsai, Fuu-Jen
Yang, Xiaobo
He, Jiang
Wu, Ying
He, Meian
Zhang, Yi
Liang, Jun
Guo, Xiuqing
Sheu, Wayne Huey-Herng
Delahanty, Ryan
Guo, Xingyi
Kubo, Michiaki
Yamamoto, Ken
Ohkubo, Takayoshi
Go, Min Jin
Liu, Jian Jun
Gan, Wei
Chen, Ching-Chu
Gao, Yong
Li, Shengxu
Lee, Nanette R.
Wu, Chen
Zhou, Xueya
Song, Huaidong
Yao, Jie
Lee, I-Te
Long, Jirong
Tsunoda, Tatsuhiko
Akiyama, Koichi
Takashima, Naoyuki
Cho, Yoon Shin
Ong, Rick T. H.
Lu, Ling
Chen, Chien-Hsiun
Tan, Aihua
Rice, Treva K.
Adair, Linda S.
Gui, Lixuan
Allison, Matthew
Lee, Wen-Jane
Cai, Qiuyin
Isomura, Minoru
Umemura, Satoshi
Kim, Young Jin
Seielstad, Mark
Hixson, James
Xiang, Yong-Bing
Isono, Masato
Kim, Bong-Jo
Sim, Xueling
Lu, Wei
Nabika, Toru
Lee, Juyoung
Lim, Wei-Yen
Gao, Yu-Tang
Takayanagi, Ryoichi
Kang, Dae-Hee
Wong, Tien Yin
Hsiung, ChaoAgnes
Wu, I-Chien
Juang, Jyh-Ming Jimmy
Shi, Jiajun
Choi, Bo Youl
Aung, Tin
Hu, Frank
Kim, Mi Kyung
Lim, WeiYen
Wang, Tzung-Dao
Shin, Min-Ho
Lee, Jeannette
Ji, Bu-Tian
Lee, Young-Hoon
Young, Terri L.
Shin, Dong Hoon
Chun, Byung-Yeol
Cho, Myeong-Chan
Han, Bok-Ghee
Hwu, Chii-Min
Assimes, Themistocles L.
Absher, Devin
Yan, Xiaofei
Kim, Eric
Kuo, Jane Z.
Kwon, Soonil
Taylor, Kent D.
Chen, Yii-Der I.
Rotter, Jerome I.
Qi, Lu
Zhu, Dingliang
Wu, Tangchun
Mohlke, Karen L.
Gu, Dongfeng
Mo, Zengnan
Wu, Jer-Yuarn
Lin, Xu
Miki, Tetsuro
Tai, E. Shyong
Lee, Jong-Young
Kato, Norihiro
Shu, Xiao-Ou
Tanaka, Toshihiro
TI Meta-analysis of genome-wide association studies in East Asian-ancestry
populations identifies four new loci for body mass index
SO HUMAN MOLECULAR GENETICS
LA English
DT Article
ID CORONARY-ARTERY-DISEASE; COMMON VARIANTS; BLOOD-PRESSURE; JAPANESE
POPULATION; GENETIC-VARIANTS; SUSCEPTIBILITY LOCI; DRINKING BEHAVIOR;
ADULT OBESITY; QT INTERVAL; RISK LOCI
AB Recent genetic association studies have identified 55 genetic loci associated with obesity or body mass index (BMI). The vast majority, 51 loci, however, were identified in European-ancestry populations. We conducted a meta-analysis of associations between BMI and similar to 2.5 million genotyped or imputed single nucleotide polymorphisms among 86 757 individuals of Asian ancestry, followed by in silico and de novo replication among 7488-47 352 additional Asian-ancestry individuals. We identified four novel BMI-associated loci near the KCNQ1 (rs2237892, P = 9.29 x 10(-13)), ALDH2/MYL2 (rs671, P = 3.40 x 10(-11); rs12229654, P = 4.56 x 10(-9)), ITIH4 (rs2535633, P = 1.77 x 10(-18)) and NT5C2 (rs11191580, P = 3.83 x 10(-8)) genes. The association of BMI with rs2237892, rs671 and rs12229654 was significantly stronger among men than among women. Of the 51 BMI-associated loci initially identified in European-ancestry populations, we confirmed eight loci at the genome-wide significance level (P < 5.0 x 10(-8)) and an additional 14 at P < 1.0 x 10(-3) with the same direction of effect as reported previously. Findings from this analysis expand our knowledge of the genetic basis of obesity.
C1 [Wen, Wanqing; Zheng, Wei; Delahanty, Ryan; Guo, Xingyi; Long, Jirong; Cai, Qiuyin; Shi, Jiajun; Shu, Xiao-Ou] Vanderbilt Univ, Div Epidemiol, Vanderbilt Epidemiol Ctr, Dept Med,Vanderbilt Ingram Canc Ctr,Sch Med, Nashville, TN 37203 USA.
[Okada, Yukinori] RIKEN Ctr Integrat Med Sci, Lab Stat Anal, Yokohama, Kanagawa, Japan.
[Kubo, Michiaki] RIKEN Ctr Integrat Med Sci, Lab Genotyping Dev, Yokohama, Kanagawa, Japan.
[Tsunoda, Tatsuhiko] RIKEN Ctr Integrat Med Sci, Lab Med Sci Math, Yokohama, Kanagawa, Japan.
[Tanaka, Toshihiro] RIKEN Ctr Integrat Med Sci, Lab Cardiovasc Dis, Yokohama, Kanagawa, Japan.
[Okada, Yukinori; Tanaka, Toshihiro] Tokyo Med & Dent Univ, Dept Human Genet & Dis Divers, Grad Sch Med & Dent Sci, Tokyo, Japan.
[Takeuchi, Fumihiko; Akiyama, Koichi; Isono, Masato; Kato, Norihiro] Natl Ctr Global Hlth & Med, Dept Gene Diagnost & Therapeut, Res Inst, Tokyo, Japan.
[Tabara, Yasuharu] Kyoto Univ, Grad Sch Med, Ctr Genom Med, Kyoto, Japan.
[Hwang, Joo-Yeon; Go, Min Jin; Cho, Yoon Shin; Kim, Young Jin; Kim, Bong-Jo; Lee, Juyoung; Han, Bok-Ghee; Lee, Jong-Young] Natl Inst Hlth, Ctr Genome Sci, Chungcheongbuk Do, South Korea.
[Dorajoo, Rajkumar; Liu, Jian Jun; Ong, Rick T. H.] Agcy Sci Technol & Res, Genome Inst Singapore, Singapore, Singapore.
[Dorajoo, Rajkumar] Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, Dept Genom Common Dis, Sch Publ Hlth, London, England.
[Li, Huaixing; Gan, Wei; Lu, Ling; Lin, Xu] Chinese Acad Sci, Key Lab Nutr & Metab, Inst Nutr Sci, Shanghai Inst Biol Sci, Shanghai 200031, Peoples R China.
[Li, Huaixing; Gan, Wei; Lu, Ling; Lin, Xu] Chinese Acad Sci, Grad Sch, Shanghai 200031, Peoples R China.
[Tsai, Fuu-Jen; Chen, Ching-Chu; Chen, Chien-Hsiun; Wu, Jer-Yuarn] China Med Univ Hosp, Sch Chinese Med, Taichung, Taiwan.
[Tsai, Fuu-Jen] China Med Univ Hosp, Dept Med Genet, Taichung, Taiwan.
[Chen, Ching-Chu] China Med Univ Hosp, Dept Med, Div Endocrinol & Metab, Taichung, Taiwan.
[Tsai, Fuu-Jen] Asia Univ, Dept Hlth & Nutr Biotechnol, Taichung, Taiwan.
[Yang, Xiaobo] Guangxi Med Univ, Dept Occupat Hlth & Environm Hlth, Sch Publ Hlth, Nanning, Guangxi, Peoples R China.
[Yang, Xiaobo; Gao, Yong; Tan, Aihua; Mo, Zengnan] Guangxi Med Univ, Ctr Genom & Personalized Med, Nanning, Guangxi, Peoples R China.
[He, Jiang; Li, Shengxu] Tulane Univ, Sch Publ Hlth & Trop Med, Dept Epidemiol, New Orleans, LA USA.
[Wu, Ying; Mohlke, Karen L.] Univ N Carolina, Dept Genet, Chapel Hill, NC USA.
[He, Meian; Gui, Lixuan; Wu, Tangchun] Huazhong Univ Sci & Technol, Dept Occupat & Environm Hlth, Wuhan 430030, Hubei, Peoples R China.
[He, Meian; Gui, Lixuan; Wu, Tangchun] Huazhong Univ Sci & Technol, Minist Educ, Key Lab Environm & Hlth, Sch Publ Hlth,Tongji Med Coll, Wuhan 430030, Hubei, Peoples R China.
[Zhang, Yi; Zhu, Dingliang] Shanghai Jiao Tong Univ, Sch Med, Shanghai Ruijin Hosp, State Key Lab Med Genet, Shanghai 200030, Peoples R China.
[Zhang, Yi; Zhu, Dingliang] Shanghai Res Inst Hypertens, Shanghai, Peoples R China.
[Liang, Jun] Southeast Univ, Dept Endocrinol, Xuzhou Cent Hosp, Xuzhou Clin Sch,Xuzhou Med Coll,Affiliated Hosp, Xuzhou 221009, Jiangsu, Peoples R China.
[Guo, Xiuqing; Yao, Jie; Yan, Xiaofei; Kim, Eric; Kwon, Soonil; Taylor, Kent D.; Chen, Yii-Der I.; Rotter, Jerome I.] Harbor UCLA Med Ctr, Inst Translat Genom & Populat Sci, Los Angeles Biomed Res Inst, Torrance, CA 90509 USA.
[Guo, Xiuqing; Yao, Jie; Yan, Xiaofei; Kim, Eric; Kwon, Soonil; Taylor, Kent D.; Chen, Yii-Der I.; Rotter, Jerome I.] Harbor UCLA Med Ctr, Dept Pediat, Torrance, CA 90509 USA.
[Sheu, Wayne Huey-Herng; Lee, I-Te] Taichung Vet Gen Hosp, Dept Internal Med, Div Endocrinol & Metab, Taichung, Taiwan.
[Sheu, Wayne Huey-Herng] Natl Def Med Ctr, Coll Med, Taipei, Taiwan.
[Sheu, Wayne Huey-Herng; Hwu, Chii-Min] Natl Yang Ming Univ, Sch Med, Taipei 112, Taiwan.
[Yamamoto, Ken] Kyushu Univ, Med Inst Bioregulat, Dept Mol Genet, Fukuoka 812, Japan.
[Ohkubo, Takayoshi] Tohoku Univ, Grad Sch Pharmaceut Sci, Dept Planning Drug Dev & Clin Evaluat, Sendai, Miyagi 980, Japan.
[Ohkubo, Takayoshi; Takashima, Naoyuki] Shiga Univ Med Sci, Dept Hlth Sci, Otsu, Shiga 52021, Japan.
[Gao, Yong] Guangxi Med Univ, Coll Gen Practice, Nanning, Guangxi, Peoples R China.
[Lee, Nanette R.] Univ San Carlos, USC Off Populat Studies Fdn Inc, Cebu, Philippines.
[Wu, Chen] Chinese Acad Med Sci, Canc Inst & Hosp, State Key Lab Mol Oncol, Beijing 100730, Peoples R China.
[Wu, Chen] Peking Union Med Coll, Beijing 100021, Peoples R China.
[Zhou, Xueya] Tsinghua Natl Lab Informat Sci & Technol, Bioinformat Div, Beijing, Peoples R China.
[Song, Huaidong] Shanghai Jiao Tong Univ, State Key Lab Med Genom, Ruijin Hosp, Mol Med Ctr,Shanghai Inst Endocrinol,Sch Med, Shanghai 200030, Peoples R China.
[Lee, I-Te] Chung Shan Med Univ, Dept Med, Taichung, Taiwan.
[Cho, Yoon Shin] Hallym Univ, Dept Biomed Sci, Gangwon Do, South Korea.
[Ong, Rick T. H.] Natl Univ Singapore, NUS Grad Sch Integrat Sci & Engn, Singapore 117548, Singapore.
[Ong, Rick T. H.; Sim, Xueling] Natl Univ Singapore, Ctr Mol Epidemiol, Singapore 117548, Singapore.
[Chen, Chien-Hsiun; Wu, Jer-Yuarn] Acad Sinica, Inst Biomed Sci, Taipei, Taiwan.
[Rice, Treva K.] Washington Univ, Sch Med, Div Biostat, St Louis, MO 63110 USA.
[Adair, Linda S.] Univ N Carolina, Dept Nutr, Chapel Hill, NC USA.
[Allison, Matthew] Univ Calif San Diego, Dept Family & Prevent Med, La Jolla, CA 92093 USA.
[Kuo, Jane Z.] Univ Calif San Diego, NShiley Eye Ctr, Dept Ophthalmol, La Jolla, CA 92093 USA.
[Lee, Wen-Jane] Taichung Vet Gen Hosp, Dept Med Res, Taichung, Taiwan.
[Lee, Wen-Jane] Tunghai Univ, Dept Social Work, Taichung 40704, Taiwan.
[Isomura, Minoru; Nabika, Toru] Shimane Univ, Dept Funct Pathol, Sch Med, Izumo, Shimane, Japan.
[Umemura, Satoshi] Yokohama City Univ, Sch Med, Dept Med Sci & Cardiorenal Med, Yokohama, Kanagawa 232, Japan.
[Seielstad, Mark] Univ Calif San Francisco, Inst Human Genet, San Francisco, CA 94143 USA.
[Hixson, James] Univ Texas Houston, Sch Publ Hlth, Ctr Human Genet, Houston, TX USA.
[Xiang, Yong-Bing] Shanghai Jiao Tong Univ, Shanghai Canc Inst, Renji Hosp, Sch Med, Shanghai 200030, Peoples R China.
[Lu, Wei] Shanghai Municipal Ctr Dis Control & Prevent, Shanghai, Peoples R China.
[Lim, Wei-Yen; Lim, WeiYen; Lee, Jeannette; Tai, E. Shyong] Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore 117548, Singapore.
[Wong, Tien Yin; Aung, Tin] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Ophthalmol, Singapore 117595, Singapore.
[Tai, E. Shyong] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Med, Singapore 117595, Singapore.
[Tai, E. Shyong] Natl Univ Hlth Syst, Singapore, Singapore.
[Gao, Yu-Tang] Shanghai Jiao Tong Univ, Dept Epidemiol, Shanghai Canc Inst, Shanghai 200030, Peoples R China.
[Takayanagi, Ryoichi] Kyushu Univ, Grad Sch Med Sci, Dept Med & Bioregulatory Sci, Fukuoka 812, Japan.
[Kang, Dae-Hee] Seoul Natl Univ, Coll Med, Dept Prevent Med, Seoul, South Korea.
[Wong, Tien Yin; Aung, Tin] Singapore Natl Eye Ctr, Singapore Eye Res Inst, Singapore, Singapore.
[Hsiung, ChaoAgnes; Wu, I-Chien] Natl Hlth Res Inst, Inst Populat Hlth Sci, Zhunan, Taiwan.
[Juang, Jyh-Ming Jimmy; Wang, Tzung-Dao] Natl Taiwan Univ Hosp, Ctr Cardiovasc, Taipei, Taiwan.
[Juang, Jyh-Ming Jimmy; Wang, Tzung-Dao] Natl Taiwan Univ Hosp, Dept Internal Med, Div Cardiol, Taipei 100, Taiwan.
[Choi, Bo Youl; Kim, Mi Kyung] Hanyang Univ, Dept Prevent Med, Coll Med, Seoul 133791, South Korea.
[Hu, Frank] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Hu, Frank; Qi, Lu] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
[Shin, Min-Ho] Chonnam Natl Univ, Sch Med, Dept Prevent Med, Kwangju, South Korea.
[Ji, Bu-Tian] NCI, Div Canc Epidemiol & Genet, Rockville, MD USA.
[Lee, Young-Hoon] Wonkwang Univ, Coll Med, Dept Prevent Med, Iksan, South Korea.
[Lee, Young-Hoon] Wonkwang Univ, Coll Med, Inst Wonkwang Med Sci, Iksan, South Korea.
[Young, Terri L.] Duke Univ, Med Ctr, Dept Ophthalmol, Durham, NC 27710 USA.
[Young, Terri L.] Duke Natl Univ Singapore, Grad Sch Med, Div Neurosci, Singapore, Singapore.
[Shin, Dong Hoon] Keimyung Univ, Sch Med, Dept Prevent Med, Taegu, South Korea.
[Chun, Byung-Yeol] Kyungpook Natl Univ, Dept Prevent Med, Sch Med, Taegu, South Korea.
[Chun, Byung-Yeol] Kyungpook Natl Univ, Hlth Promot Res Ctr, Taegu, South Korea.
[Cho, Myeong-Chan] Natl Inst Hlth, Chungcheongbuk Do, South Korea.
[Hwu, Chii-Min] Taipei Vet Gen Hosp, Dept Med, Sect Endocrinol & Metab, Taipei, Taiwan.
[Assimes, Themistocles L.] Stanford Univ, Dept Med, Sch Med, Stanford, CA 94305 USA.
[Absher, Devin] HudsonAlpha Inst Biotechnol, Huntsville, AL USA.
[Qi, Lu] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA.
[Qi, Lu] Harvard Univ, Sch Med, Boston, MA USA.
[Gu, Dongfeng] Chinese Acad Med Sci, Fuwai Hosp, Dept Evidence Based Med, Beijing 100730, Peoples R China.
[Gu, Dongfeng] Peking Union Med Coll, Beijing 100021, Peoples R China.
[Gu, Dongfeng] Natl Ctr Cardiovasc Dis, Beijing, Peoples R China.
[Mo, Zengnan] Guangxi Med Univ, Affiliated Hosp 1, Inst Urol & Nephrol, Nanning, Guangxi, Peoples R China.
[Miki, Tetsuro] Ehime Univ, Dept Geriatr Med, Grad Sch Med, Toon, Japan.
[Tai, E. Shyong] Duke Natl Univ Singapore, Grad Sch Med, Singapore, Singapore.
[Tanaka, Toshihiro] Tokyo Med & Dent Univ, Div Dis Divers, Bioresource Res Ctr, Tokyo, Japan.
RP Shu, XO (reprint author), Vanderbilt Univ, Sch Med, Vanderbilt Epidemiol Ctr, 2525 West End Ave,Suite 600 IMPH, Nashville, TN 37203 USA.
EM xiao-ou.shu@vanderbilt.edu
RI Tanaka, Toshihiro/J-9310-2014; Hsiung, Chao Agnes/E-3994-2010; Tsunoda,
Tatsuhiko/K-2061-2014; Tsai, Fuu-Jen/J-4140-2015; Yang,
Xiaobo/G-3854-2016; Kubo, Michiaki/N-7947-2015; WU, I-CHIEN/C-1515-2011;
OI Tanaka, Toshihiro/0000-0001-6201-9784; Tai, E
Shyong/0000-0003-2929-8966; WU, I-CHIEN/0000-0002-6916-8165; Allison,
Matthew/0000-0003-0777-8272; Assimes, Themistocles/0000-0003-2349-0009
FU US National Institutes of Health [R37CA070867, R01CA082729, R01CA124558,
R01CA148667, R01CA122364]; Vanderbilt University School of Medicine;
Ministry of Education, Culture, Sports, Science, and Technology, Japan
[20390185, 21390099, 19659163, 16790336, 12204008, 15790293, 16590433,
17790381, 18390192, 18590265, 18590587, 18590811, 19590929, 19650188,
19790423, 17390186, 20390184, 21390223]; Ministry of Health, Labor and
Welfare, Japan [H15-Longevity005, H17-longevity-003, H16-kenko-001,
H18-longevity (kokusai), H11-longevity-020, H17-Kenkou-007,
H17-pharmaco-common003, H18-Junkankitou (Seishuu)-Ippan-012,
H20-Junkankitou (Seishuu)-Ippan-009, H20-Junkankitou
(Seishuu)-Ippan-013]; Science and Technology Incubation Program in
Advanced Regions, Japan Science and Technology Agency; Japan Society for
the Promotion of Science (JSPS), Tokyo, Japan [16.54041, 18.54042,
19.7152, 20.7198, 20.7477, 20.54043]; Health Science Research Grants and
Medical Technology Evaluation Research Grants from the Ministry of
Health, Labor and Welfare, Japan; Japan Atherosclerosis Prevention Fund;
Uehara Memorial Foundation; Takeda Medical Research Foundation; Japan
Research Foundation for Clinical Pharmacology; Korea Center for Disease
Control and Prevention [4845-301, 4851-302, 4851-307]; Korea National
Institute of Health [2012-N73002-00]; Singapore Ministry of Health's
National Medical Research Council; Singapore National Research
Foundation; Singapore Biomedical Research Council (BMRC); National High
Technology Research and Development Program [2009AA022704]; Knowledge
Innovation Program [KSCX2-EW-R-10]; National Natural Science Foundation
of China [30930081, 81021002, 81170734]; National Key Basic Research
Program of China [2012CB524900]; National Heart, Lung, and Blood
Institute, National Institutes of Health, Bethesda, MD [U01HL072507,
R01HL087263, R01HL090682]; National Institutes of Health [DK078150,
TW05596, HL085144, TW008288, RR20649, E510126, DK56350]; National Heart,
Lung, and Blood Institute [HL071981]; National Institute of Diabetes and
Digestive and Kidney Diseases [DK091718, DK078616]; Boston Obesity
Nutrition Research Center [DK46200]; United States Israel Binational
Science Foundation [2011036]; National Heart, Lung, and Blood Institute
(NHLBI) [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, RR-024156]; NHLBI [N02-HL-6-4278]; NHLBI.
[HL087647]; National Health Research Institutes [PH-100-SP-01]; National
Health Research Institutes. [BS-094-PP-01, PH-100-PP-03]; National
Taiwan University Hospital [NTUH.98-N1266, NTUH100-N1775, NTUH101-N2010,
NTUH101-N, VN101-04, NTUH 101-S1784]; National Science Council of Taiwan
[NSC96-2314-B-002-151, NSC-982314-B-002-122-MY2, NSC 100-2314-B-002-115,
NSC 96-2314-B-002-152, NSC 101-2325-002-078]; National Science Council
[NSC 98-2314-B-075A-002-MY3]; Taichung Veterans General Hospital,
Taichung, Taiwan [TCVGH-1013001 C, TCVGH-1013002D]; Academia Sinica
Genomic Medicine Multicenter Study [Academia Sinica 40-05-GMM]; Academia
Sinica, Taiwan; National Center for Genome Medicine at Academia Sinica
(NC GM) of the National Core Facility Program for Biotechnology (NCFPB)
[NSC-101-2319-B-001-001]; Translational Resource Center for Genomic
Medicine (TRC) of the National Research Program for Biopharmaceuticals
(NRPB), National Science Council, Taiwan [NSC-101-2325-B-001-035];
[R01CA064277]; [R01CA092585]
FX This work was supported by the sources listed below. The funding
information provided below pertains to the participating studies that
contributed summary statistics to this meta-analysis. The funders of the
original studies had no role in study design, data collection and
analysis, decision to publish or preparation of this manuscript. The
SGWAS was supported in part by US National Institutes of Health grants
R37CA070867 (to W.Z.), R01CA082729 (to X.-O. S.), R01CA124558 (to W.Z.),
R01CA148667 (to W.Z.) and R01CA122364 (G.Y.), as well as Ingram
Professorship and Research Reward funds from the Vanderbilt University
School of Medicine. Participating studies (grant support) in the
Shanghai Genome-Wide Association Studies (SGWAS) are as follows:
Shanghai Women's Health Study (R37CA070867 to W.Z.), Shanghai Men's
Health Study (R01CA082729 to X.-O.S.), Shanghai Breast Cancer Study
(R01CA064277 to X.-O.S.) and Shanghai Endometrial Cancer Study
(R01CA092585 to X.-O.S.). We thank Regina Courtney for DNA preparation
and Jing He for data processing and analyses. The JMGP was supported by
Grants for Scientific Research (Priority Areas "Medical Genome Science
(Millennium Genome Project)" and "Applied Genomics", Leading Project for
Personalized Medicine, and Scientific Research 20390185, 21390099,
19659163, 16790336, 12204008, 15790293, 16590433, 17790381, 17790381,
18390192, 18590265, 18590587, 18590811, 19590929, 19650188, 19790423,
17390186, 20390184 and 21390223) from the Ministry of Education,
Culture, Sports, Science, and Technology, Japan; a Grants-in-Aid
[H15-Longevity005, H17-longevity-003, H16-kenko-001, H18-longevity
(kokusai), H11-longevity-020, H17-Kenkou-007, H17-pharmaco-common003,
H18-Junkankitou (Seishuu)-Ippan-012 and H20-Junkankitou
(Seishuu)-Ippan-009, 013] from the Ministry of Health, Labor and
Welfare, Health and Labor Sciences Research Grants, Japan; a Science and
Technology Incubation Program in Advanced Regions, Japan Science and
Technology Agency; a Grants-in-Aid from the Japan Society for the
Promotion of Science (JSPS) fellows (16.54041, 18.54042, 19.7152,
20.7198, 20.7477 and 20.54043), Tokyo, Japan; Health Science Research
Grants and Medical Technology Evaluation Research Grants from the
Ministry of Health, Labor and Welfare, Japan; the Japan Atherosclerosis
Prevention Fund; the Uehara Memorial Foundation; the Takeda Medical
Research Foundation; and the Japan Research Foundation for Clinical
Pharmacology. The KARE project was supported by a grant from the Korea
Center for Disease Control and Prevention (4845-301, 4851-302,
4851-307), and intramural grant from the Korea National Institute of
Health (2012-N73002-00). The 5P2 and SiMES were supported by the
Singapore Ministry of Health's National Medical Research Council under
its Individual Research Grant funding scheme, the Singapore National
Research Foundation under its Clinician Scientist Award and Singapore
Translational Research Investigator Award funding schemes, which are
administered by the Singapore Ministry of Health's National Medical
Research Council and the Singapore Biomedical Research Council (BMRC)
individual research grant funding scheme. The NHAPC study is supported
by research grants including the National High Technology Research and
Development Program (2009AA022704), Knowledge Innovation Program
(KSCX2-EW-R-10), the National Natural Science Foundation of China
(30930081, 81021002, 81170734) and the National Key Basic Research
Program of China (2012CB524900).; GenSalt is supported by research
grants (U01HL072507, R01HL087263 and R01HL090682) from the National
Heart, Lung, and Blood Institute, National Institutes of Health,
Bethesda, MD. The CLHNS was supported by National Institutes of Health
grants DK078150, TW05596, HL085144 and TW008288 and pilot funds from
RR20649, E510126 and DK56350. We thank the Office of Population Studies
Foundation research and data collection teams for the Cebu Longitudinal
Health and Nutrition Survey. The CRC was supported by grants from the
National Heart, Lung, and Blood Institute (HL071981), the National
Institute of Diabetes and Digestive and Kidney Diseases (DK091718 and
DK078616), the Boston Obesity Nutrition Research Center (DK46200) and
United States Israel Binational Science Foundation Grant 2011036. The
MESA and MESA SHARe project are conducted and supported by contracts
N01-HC-95159 through N01-HC-95169 and RR-024156 from the National Heart,
Lung, and Blood Institute (NHLBI). Funding for MESA SHARe genotyping was
provided by NHLBI Contract N02-HL-6-4278. The authors thank the
participants of the MESA study, the Coordinating Center, MESA
investigators and study staff for their valuable contributions. A full
list of participating MESA investigators and institutions can be found
at http://www. mesa-nhlbi.org. The TAICHI Metabochip study was supported
by NHLBI grant HL087647. Financial support for HALST was through grants
from the National Health Research Institutes (PH-100-SP-01). The
SAPPHERe was supported by grants from the National Health Research
Institutes (BS-094-PP-01 & PH-100-PP-03). The TCAGEN was partially
supported by grants NTUH.98-N1266, NTUH100-N1775, NTUH101-N2010,
NTUH101-N, VN101-04 and NTUH 101-S1784 from National Taiwan University
Hospital, NSC 96-2314-B-002-152 and NSC 101-2325-002-078. The TACT was
supported by grants from the National Science Council of Taiwan
(NSC96-2314-B-002-151, NSC-982314-B-002-122-MY2 and NSC
100-2314-B-002-115). The Taiwan Dragon and TACD were supported by grants
from the National Science Council (NSC 98-2314-B-075A-002-MY3) and
Taichung Veterans General Hospital, Taichung, Taiwan (TCVGH-1013001 C;
TCVGH-1013002D). The Taiwan Genome Wide Association Study was supported
by the Academia Sinica Genomic Medicine Multicenter Study (Academia
Sinica 40-05-GMM) and Search and build the biosignatures for type 2
diabetes complications in the Han Chinese population (Academia Sinica
23-2 h), Academia Sinica, Taiwan, and the National Center for Genome
Medicine at Academia Sinica (NC GM, NSC-101-2319-B-001-001) of the
National Core Facility Program for Biotechnology (NCFPB) and the
Translational Resource Center for Genomic Medicine (TRC,
NSC-101-2325-B-001-035) of the National Research Program for
Biopharmaceuticals (NRPB), National Science Council, Taiwan.
NR 64
TC 25
Z9 25
U1 2
U2 26
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0964-6906
EI 1460-2083
J9 HUM MOL GENET
JI Hum. Mol. Genet.
PD OCT 15
PY 2014
VL 23
IS 20
BP 5492
EP 5504
DI 10.1093/hmg/ddu248
PG 13
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA AQ9UO
UT WOS:000343202400016
PM 24861553
ER
PT J
AU Feng, Y
Stram, DO
Rhie, SK
Millikan, RC
Ambrosone, CB
John, EM
Bernstein, L
Zheng, W
Olshan, AF
Hu, JJ
Ziegler, RG
Nyante, S
Bandera, EV
Ingles, SA
Press, MF
Deming, SL
Rodriguez-Gil, JL
Palmer, JR
Olopade, OI
Huo, DZ
Adebamowo, CA
Ogundiran, T
Chen, GK
Stram, A
Park, K
Rand, KA
Chanock, SJ
Le Marchand, L
Kolonel, LN
Conti, DV
Easton, D
Henderson, BE
Haiman, CA
AF Feng, Ye
Stram, Daniel O.
Rhie, Suhn Kyong
Millikan, Robert C.
Ambrosone, Christine B.
John, Esther M.
Bernstein, Leslie
Zheng, Wei
Olshan, Andrew F.
Hu, Jennifer J.
Ziegler, Regina G.
Nyante, Sarah
Bandera, Elisa V.
Ingles, Sue A.
Press, Michael F.
Deming, Sandra L.
Rodriguez-Gil, Jorge L.
Palmer, Julie R.
Olopade, Olufunmilayo I.
Huo, Dezheng
Adebamowo, Clement A.
Ogundiran, Temidayo
Chen, Gary K.
Stram, Alex
Park, Karen
Rand, Kristin A.
Chanock, Stephen J.
Le Marchand, Loic
Kolonel, Laurence N.
Conti, David V.
Easton, Douglas
Henderson, Brian E.
Haiman, Christopher A.
TI A comprehensive examination of breast cancer risk loci in African
American women
SO HUMAN MOLECULAR GENETICS
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; SUSCEPTIBILITY LOCI; GENETIC POLYMORPHISMS;
IDENTIFIES 2; POPULATION; EPIDEMIOLOGY; VARIANT; COHORT
AB Genome-wide association studies have identified 73 breast cancer risk variants mainly in European populations. Given considerable differences in linkage disequilibrium structure between populations of European and African ancestry, the known risk variants may not be informative for risk in African ancestry populations. In a previous fine-mapping investigation of 19 breast cancer loci, we were able to identify SNPs in four regions that better captured risk associations in African American women. In this study of breast cancer in African American women (3016 cases, 2745 controls), we tested an additional 54 novel breast cancer risk variants. Thirty-eight variants (70%) were found to have an association with breast cancer in the same direction as previously reported, with eight (15%) replicating at P < 0.05. Through fine-mapping, in three regions (1q32, 3p24, 1005), we identified variants that better captured associations with overall breast cancer or estrogen receptor positive disease. We also observed suggestive associations with variants (at P < 5 x 10(-6)) in three separate regions (6q25, 14q13, 22q12) that may represent novel risk variants. Directional consistency of association observed for similar to 65-70% of currently known genetic variants for breast cancer in women of African ancestry implies a shared functional common variant at most loci. To validate and enhance the spectrum of alleles that define associations at the known breast cancer risk loci, as well as genome-wide, will require even larger collaborative efforts in women of African ancestry.
C1 [Feng, Ye; Stram, Daniel O.; Rhie, Suhn Kyong; Ingles, Sue A.; Chen, Gary K.; Stram, Alex; Park, Karen; Rand, Kristin A.; Conti, David V.; Henderson, Brian E.; Haiman, Christopher A.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA.
[Feng, Ye; Stram, Daniel O.; Rhie, Suhn Kyong; Ingles, Sue A.; Press, Michael F.; Chen, Gary K.; Stram, Alex; Park, Karen; Rand, Kristin A.; Conti, David V.; Henderson, Brian E.; Haiman, Christopher A.] Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Los Angeles, CA 90033 USA.
[Press, Michael F.] Univ So Calif, Keck Sch Med, Dept Pathol, Los Angeles, CA 90033 USA.
[Millikan, Robert C.; Olshan, Andrew F.] Univ N Carolina, Dept Epidemiol, Gillings Sch Global Publ Hlth, Chapel Hill, NC USA.
[Millikan, Robert C.; Olshan, Andrew F.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA.
[Ambrosone, Christine B.] Roswell Pk Canc Inst, Dept Canc Prevent & Control, Buffalo, NY 14263 USA.
[John, Esther M.] Canc Prevent Inst Calif, Fremont, CA USA.
[John, Esther M.] Stanford Univ, Sch Med, Div Epidemiol, Dept Hlth Res & Policy, Stanford, CA 94305 USA.
[John, Esther M.] Stanford Univ, Sch Med, Stanford Canc Inst, Stanford, CA 94305 USA.
[Bernstein, Leslie] City Hope Natl Med Ctr, Beckman Res Inst, Dept Populat Sci, Div Canc Etiol, Duarte, CA USA.
[Zheng, Wei; Deming, Sandra L.] Vanderbilt Univ, Sch Med, Div Epidemiol, Dept Med,Vanderbilt Epidemiol Ctr, Nashville, TN 37212 USA.
[Zheng, Wei; Deming, Sandra L.] Vanderbilt Univ, Sch Med, Vanderbilt Ingram Canc Ctr, Nashville, TN 37212 USA.
[Hu, Jennifer J.; Rodriguez-Gil, Jorge L.] Univ Miami, Miller Sch Med, Sylvester Comprehens Canc Ctr, Miami, FL 33136 USA.
[Hu, Jennifer J.; Rodriguez-Gil, Jorge L.] Univ Miami, Miller Sch Med, Dept Epidemiol & Publ Hlth, Miami, FL 33136 USA.
[Ziegler, Regina G.; Chanock, Stephen J.] NCI, Epidemiol & Biostat Program, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Nyante, Sarah] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Bandera, Elisa V.] Rutgers Canc Inst New Jersey, New Brunswick, NJ USA.
[Palmer, Julie R.] Boston Univ, Slone Epidemiol Ctr, Boston, MA 02215 USA.
[Olopade, Olufunmilayo I.] Univ Chicago, Ctr Clin Canc Genet & Global Hlth, Dept Med, Chicago, IL 60637 USA.
[Huo, Dezheng] Univ Chicago, Dept Hlth Studies, Chicago, IL 60637 USA.
[Adebamowo, Clement A.] Univ Maryland, Dept Epidemiol & Prevent Med, Baltimore, MD 21201 USA.
[Ogundiran, Temidayo] Univ Ibadan, Dept Surg, Coll Med, Ibadan, Nigeria.
[Le Marchand, Loic; Kolonel, Laurence N.] Univ Hawaii, Ctr Canc, Program Epidemiol, Honolulu, HI 96822 USA.
[Easton, Douglas] Univ Cambridge, Ctr Canc Genet Epidemiol, Dept Publ Hlth & Primary Care, Cambridge, England.
RP Haiman, CA (reprint author), USC Norris Comprehens Canc Ctr, Harlyne Norris Res Tower,1450 Biggy St,Room 1504, Los Angeles, CA 90033 USA.
EM haiman@usc.edu
RI Bandera, Elisa/M-4169-2014
OI Bandera, Elisa/0000-0002-8789-2755
FU Department of Defense Breast Cancer Research Program Era of Hope Scholar
Award [W81XWH-08-1-0383]; Norris Foundation; National Institutes of
Health [R01-CA63464, R37-CA54281, UM1-CA164973]; CARE (National
Institute for Child Health and Development grant) [N01-HD-3-3175, K05
CA136967]; WCHS (US Army Medical Research and Material Command
(USAMRMC)) [DAMD-17-01-0-0334]; National Institutes of Health.
[R01-CA100598]; Breast Cancer Research Foundation; SFBCS (National
Institutes of Health) [R01-CA77305]; United States Army Medical Research
Program [DAMD17-96-6071]; CBCS (National Institutes of Health
Specialized Program of Research Excellence in Breast Cancer)
[P50-CA58223]; Center for Environmental Health and Susceptibility
National Institute of Environmental Health Sciences, National Institutes
of Health [P30-E510126]; PLCO (Intramural Research Program, National
Cancer Institute, National Institutes of Health); NBHS (National
Institutes of Health) [R01-CA100374]; WFBC (National Institutes of
Health) [R01-CA73629]; National Cancer Institute [UM1 CA164920];
National Institutes of Health Specialized Program of Research Excellence
in Breast Cancer [P50-CA125183]; National Cancer Institute. [R01
CA142996, R01-CA141712, R01 CA89085, R01-CA098663, R01-CA058420];
Florida Bankhead-Coley Cancer Research Program [10BG-04]; European
Community's Seventh Framework Programme [223175
(HEALTH-F2-2009-223175)]; Cancer Research UK [C1287/A10118,
C1287/A10710, C12292/A11174, C1281/A12014, C5047/A8384, C5047/A15007,
C5047/A10692]; National Institutes of Health . [CA128978]; Post-Cancer
GWAS initiative (the GAME-ON initiative) [1U19 CA148537, 1U19 CA148065,
1U19CA148112]; Department of Defense [W81XWH-10-1-0341]; Canadian
Institutes of Health Research (CIHR); Komen Foundation for the Cure;
Ovarian Cancer Research Fund; [U19-CA148065]
FX This research was supported by a Department of Defense Breast Cancer
Research Program Era of Hope Scholar Award to C.A.H. (W81XWH-08-1-0383),
the Norris Foundation and U19-CA148065. Each of the participating
studies was supported by the following grants: MEC (National Institutes
of Health grants R01-CA63464, R37-CA54281 and UM1-CA164973); CARE
(National Institute for Child Health and Development grant
N01-HD-3-3175, K05 CA136967); WCHS (US Army Medical Research and
Material Command (USAMRMC) grant DAMD-17-01-0-0334, the National
Institutes of Health grant R01-CA100598 and in part by a grant from the
Breast Cancer Research Foundation); SFBCS (National Institutes of Health
grant R01-CA77305 and United States Army Medical Research Program grant
DAMD17-96-6071); CBCS (National Institutes of Health Specialized Program
of Research Excellence in Breast Cancer, grant number P50-CA58223 and
Center for Environmental Health and Susceptibility National Institute of
Environmental Health Sciences, National Institutes of Health, grant
number P30-E510126); PLCO (Intramural Research Program, National Cancer
Institute, National Institutes of Health); NBHS (National Institutes of
Health grant R01-CA100374); WFBC (National Institutes of Health grant
R01-CA73629). The Breast Cancer Family Registry (BCFR) was supported by
grant UM1 CA164920 from the National Cancer Institute. The content of
this manuscript does not necessarily reflect the views or policies of
the National Cancer Institute or any of the collaborating centers in the
BCFR, nor does mention of trade names, commercial products, or
organizations imply endorsement by the US Government or the BCFR;
O.I.O., D.H., C.A.A., T.O.O. and the replication analyses were supported
by National Institutes of Health Specialized Program of Research
Excellence in Breast Cancer, grant number P50-CA125183 and National
Cancer Institute, R01 CA142996, R01-CA141712 and R01 CA89085. J.R.P. was
supported by National Cancer Institute grants R01-CA098663 and
R01-CA058420. J.J.H. was supported by Florida Bankhead-Coley Cancer
Research Program 10BG-04. The SNPs investigated in this study were
provided from the COGS consortium and we would like to recognize the
following investigators: Per Hall (COGS), Paul Pharoah, Kyriaki
Michailidou, Manjeet K. Bolla, Qin Wang (BCAC), Andrew Berchuck (OCAC),
Rosalind A. Eeles, Douglas F. Easton, Ali Amin Al Olama, Zsofia
Kote-Jarai, Sara Benlloch (PRACTICAL), Georgia Chenevix-Trench, Antonis
Antoniou, Lesley McGuffog, Fergus Couch and Ken Offit (CIMBA), Joe
Dennis, Alison M. Dunning, Andrew Lee and Ed Dicks, Craig Luccarini and
the staff of the Centre for Genetic Epidemiology Laboratory, Javier
Benitez, Anna Gonzalez-Neira and the staff of the CNIO genotyping unit,
Jacques Simard and Daniel C. Tessier, Francois Bacot, Daniel Vincent,
Sylvie LaBoissiere and Frederic Robidoux and the staff of the McGill
University and Genome Quebec Innovation Centre, Stig E. Bojesen, 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.; Funding for the iCOGS infrastructure came from: the European
Community's Seventh Framework Programme under grant agreement number
223175 (HEALTH-F2-2009-223175) (COGS), Cancer Research UK (C1287/A10118,
C1287/A10710, C12292/A11174, C1281/A12014, C5047/A8384, C5047/A15007,
C5047/A10692), the National Institutes of Health (CA128978) and
Post-Cancer GWAS initiative (1U19 CA148537, 1U19 CA148065 and
1U19CA148112 - the GAME-ON initiative), the Department of Defense
(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 9
Z9 9
U1 1
U2 9
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0964-6906
EI 1460-2083
J9 HUM MOL GENET
JI Hum. Mol. Genet.
PD OCT 15
PY 2014
VL 23
IS 20
BP 5518
EP 5526
DI 10.1093/hmg/ddu252
PG 9
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA AQ9UO
UT WOS:000343202400018
PM 24852375
ER
PT J
AU Rees, MG
Raimondo, A
Wang, J
Ban, MR
Davis, MI
Barrett, A
Ranft, J
Jagdhuhn, D
Waterstradt, R
Baltrusch, S
Simeonov, A
Collins, FS
Hegele, RA
Gloyn, AL
AF Rees, Matthew G.
Raimondo, Anne
Wang, Jian
Ban, Matthew R.
Davis, Mindy I.
Barrett, Amy
Ranft, Jessica
Jagdhuhn, David
Waterstradt, Rica
Baltrusch, Simone
Simeonov, Anton
Collins, Francis S.
Hegele, Robert A.
Gloyn, Anna L.
TI Inheritance of rare functional GCKR variants and their contribution to
triglyceride levels in families
SO HUMAN MOLECULAR GENETICS
LA English
DT Article
ID GLUCOKINASE REGULATORY PROTEIN; GENOME-WIDE ASSOCIATION; DIABETES
THERAPY; P446L VARIANT; GENETIC-BASIS; MUTATIONS; ACTIVATORS; GLUCOSE;
COMMON; LIVER
AB Significant resources have been invested in sequencing studies to investigate the role of rare variants in complex disease etiology. However, the diagnostic interpretation of individual rare variants remains a major challenge, and may require accurate variant functional classification and the collection of large numbers of variant carriers. Utilizing sequence data from 458 individuals with hypertriglyceridemia and 333 controls with normal plasma triglyceride levels, we investigated these issues using GCKR, encoding glucokinase regulatory protein. Eighteen rare non-synonymous GCKR variants identified in these 791 individuals were comprehensively characterized by a range of biochemical and cell biological assays, including a novel high-throughput-screening based approach capable of measuring all variant proteins simultaneously. Functionally deleterious variants were collectively associated with hypertriglyceridemia, but a range of in silico prediction algorithms showed little consistency between algorithms and poor agreement with functional data. We extended our study by obtaining sequence data on family members; however, functional variants did not co-segregate with triglyceride levels. Therefore, despite evidence for their collective functional and clinical relevance, our results emphasize the low predictive value of rare GCKR variants in individuals and the complex heritability of lipid traits.
C1 [Rees, Matthew G.; Raimondo, Anne; Barrett, Amy; Gloyn, Anna L.] Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Oxford OX3 7LE, England.
[Rees, Matthew G.; Collins, Francis S.] NHGRI, NIH, Bethesda, MD 20892 USA.
[Rees, Matthew G.; Davis, Mindy I.; Simeonov, Anton] NIH, Natl Ctr Adv Translat Sci, Rockville, MD 20850 USA.
[Wang, Jian; Ban, Matthew R.; Hegele, Robert A.] Univ Western Ontario, Dept Med, London, ON N6A 3K6, Canada.
[Wang, Jian; Ban, Matthew R.; Hegele, Robert A.] Univ Western Ontario, Robarts Res Inst, Schulich Sch Med & Dent, Dept Biochem, London, ON N6A 3K6, Canada.
[Ranft, Jessica; Jagdhuhn, David; Waterstradt, Rica; Baltrusch, Simone] Univ Rostock, Inst Med Biochem & Mol Biol, D-18057 Rostock, Germany.
[Gloyn, Anna L.] Churchill Hosp, NIHR Oxford Biomed Res Ctr, ORH Trust, OCDEM, Oxford OX3 7LE, England.
RP Gloyn, AL (reprint author), Churchill Hosp, Oxford Ctr Diabet Endocrinol & Metab, Oxford OX3 7LE, England.
EM anna.gloyn@drl.ox.ac.uk
RI Hegele, Robert/G-3301-2011
FU Wellcome Trust [095101/Z/10/Z]; Heart and Stroke Foundation of Canada
[T6606]; Canadian Institutes for Health Research [MOP13430, MOP79533];
German Diabetes Association (DDG); Molecular Libraries Common Fund
Program of the National Institutes of Health; NIH HHS/United States [Z01
HG000024/HG/NHGRI]; Wellcome Trust
FX This work was supported in Oxford by the Wellcome Trust (grant number
095101/Z/10/Z); in Canada by operating grants to RAH from the Heart and
Stroke Foundation of Canada (grant number T6606) and the Canadian
Institutes for Health Research (grant numbers MOP13430, MOP79533); in
Rostock by the German Diabetes Association (DDG); and at NIH by the
Molecular Libraries Common Fund Program of the National Institutes of
Health and grant number Z01 HG000024/HG/NHGRI NIH HHS/United States to
FSC. Funding to pay the Open Access publication charges for this article
was provided by the Wellcome Trust.
NR 31
TC 5
Z9 5
U1 0
U2 6
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0964-6906
EI 1460-2083
J9 HUM MOL GENET
JI Hum. Mol. Genet.
PD OCT 15
PY 2014
VL 23
IS 20
BP 5570
EP 5578
DI 10.1093/hmg/ddu269
PG 9
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA AQ9UO
UT WOS:000343202400023
PM 24879641
ER
PT J
AU Zwicker, JD
Zhang, Y
Ren, J
Hutchinson, MR
Rice, KC
Watkins, LR
Greer, JJ
Funk, GD
AF Zwicker, Jennifer D.
Zhang, Yong
Ren, Jun
Hutchinson, Mark R.
Rice, Kenner C.
Watkins, Linda R.
Greer, John J.
Funk, Gregory D.
TI Glial TLR4 signaling does not contribute to opioid-induced depression of
respiration
SO JOURNAL OF APPLIED PHYSIOLOGY
LA English
DT Article
DE opioid; pre-Botzinger complex; rat; respiratory depression; toll-like
receptor
ID PRE-BOTZINGER COMPLEX; LONG-TERM POTENTIATION; UNDERLYING NEUROPATHIC
PAIN; EVOKED FIELD POTENTIALS; NECROSIS-FACTOR-ALPHA; TOLL-LIKE
RECEPTORS; SPINAL DORSAL-HORN; BRAIN-STEM SLICES; IN-VITRO; PREBOTZINGER
COMPLEX
AB Opioids activate glia in the central nervous system in part by activating the toll-like receptor 4 (TLR4)/myeloid differentiation 2 (MD2) complex. TLR4/MD2-mediated activation of glia by opioids compromises their analgesic actions. Glial activation is also hypothesized as pivotal in opioid-mediated reward and tolerance and as a contributor to opioid-mediated respiratory depression. We tested the contribution of TLR4 to opioid-induced respiratory depression using rhythmically active medullary slices that contain the pre-Botzinger Complex (preBotC, an important site of respiratory rhythm generation) and adult rats in vivo. Injection with DAMGO (mu-opioid receptor agonist; 50 mu M) or bath application of DAMGO (500 nM) or fentanyl (1 mu M) slowed frequency recorded from XII nerves to 40%, 40%, or 50% of control, respectively. This DAMGO-mediated frequency inhibition was unaffected by preapplication of lipopolysaccharides from Rhodobacter sphaeroides (a TLR4 antagonist, 2,000 ng/ml) or (+) naloxone (1-10 mu M, a TLR4-antagonist). Bath application of (-) naloxone (500 nM; a TLR4 and mu-opioid antagonist), however, rapidly reversed the opioid-mediated frequency decrease. We also compared the opioid-induced respiratory depression in slices in vitro in the absence and presence of bath-applied minocycline (an inhibitor of microglial activation) and in slices prepared from mice injected (ip) 18 h earlier with minocycline or saline. Minocycline had no effect on respiratory depression in vitro. Finally, the respiratory depression evoked in anesthetized rats by tail vein infusion of fentanyl was unaffected by subsequent injection of (+) naloxone, but completely reversed by (-) naloxone. These data indicate that neither activation of microglia in preBotC nor TLR4/MD2-activation contribute to opioid-induced respiratory depression.
C1 [Zwicker, Jennifer D.; Zhang, Yong; Ren, Jun; Greer, John J.; Funk, Gregory D.] Univ Alberta, Fac Med & Dent, Women & Childrens Hlth Res Inst, Dept Physiol,Neurosci & Mental Hlth Inst, Edmonton, AB T6G 2E1, Canada.
[Hutchinson, Mark R.] Univ Adelaide, Sch Med Sci, Discipline Physiol, Adelaide, SA, Australia.
[Rice, Kenner C.] NIDA, Chem Biol Res Branch, Rockville, MD USA.
[Rice, Kenner C.] NIAAA, Rockville, MD 20852 USA.
[Watkins, Linda R.] Univ Colorado, Dept Psychol, Boulder, CO 80309 USA.
[Watkins, Linda R.] Univ Colorado, Ctr Neurosci, Boulder, CO 80309 USA.
RP Funk, GD (reprint author), Univ Alberta, Dept Physiol, 3-020G Katz Grp Ctr, Edmonton, AB T6G 2E1, Canada.
EM gf@ualberta.ca
OI Hutchinson, Mark/0000-0003-2154-5950
FU Canadian Institutes for Health Research Grant [RES0006842]; Alberta
Innovates Health Solutions (AIHS); Canadian Foundation for Innovation
(CFI); Alberta Science and Research Authority; AIHS studentship; Women
and Children's Health Research Institute studentship; Australian
Research Council Research Fellowship [DP110100297]; intramural research
programs of the National Institute on Drug Abuse; National Institute of
Alcohol Abuse and Alcoholism
FX Support for this study was supported by Canadian Institutes for Health
Research Grant RES0006842, Alberta Innovates Health Solutions (AIHS),
Canadian Foundation for Innovation (CFI), and Alberta Science and
Research Authority. J. Zwicker was supported by an AIHS studentship.
G.D. Funk and J.J. Greer are AIHS Scientists. Y. Zhang was supported by
a Women and Children's Health Research Institute studentship. M.
Hutchinson is the recipient of Australian Research Council Research
Fellowship DP110100297. The work of the Drug Design and Synthesis
Section, CBRB, NIDA, and NIAAA was supported by the intramural research
programs of the National Institute on Drug Abuse and the National
Institute of Alcohol Abuse and Alcoholism.
NR 88
TC 5
Z9 6
U1 1
U2 8
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 8750-7587
EI 1522-1601
J9 J APPL PHYSIOL
JI J. Appl. Physiol.
PD OCT 15
PY 2014
VL 117
IS 8
BP 857
EP 868
DI 10.1152/japplphysiol.00534.2014
PG 12
WC Physiology; Sport Sciences
SC Physiology; Sport Sciences
GA AR0DX
UT WOS:000343238500005
PM 25103966
ER
PT J
AU Barnes, KA
Anderson, KM
Plitt, M
Martin, A
AF Barnes, Kelly Anne
Anderson, Kevin M.
Plitt, Mark
Martin, Alex
TI Individual differences in intrinsic brain connectivity predict decision
strategy
SO JOURNAL OF NEUROPHYSIOLOGY
LA English
DT Article
DE strategy; decision making; individual differences; fMRI; fcMRI
ID STATE FUNCTIONAL CONNECTIVITY; PERCEPTUAL DECISION; PREFRONTAL CORTEX;
TASK; MOTION; FMRI; ARCHITECTURE; RECOGNITION; PERFORMANCE; SOFTWARE
AB When humans are provided with ample time to make a decision, individual differences in strategy emerge. Using an adaptation of a well-studied decision making paradigm, motion direction discrimination, we probed the neural basis of individual differences in strategy. We tested whether strategies emerged from moment-to-moment reconfiguration of functional brain networks involved in decision making with task-evoked functional MRI (fMRI) and whether intrinsic properties of functional brain networks, measured at rest with functional connectivity MRI (fcMRI), were associated with strategy use. We found that human participants reliably selected one of two strategies across 2 days of task performance, either continuously accumulating evidence or waiting for task difficulty to decrease. Individual differences in decision strategy were predicted both by the degree of task-evoked activation of decision-related brain regions and by the strength of pretask correlated spontaneous brain activity. These results suggest that spontaneous brain activity constrains strategy selection on perceptual decisions.
C1 [Barnes, Kelly Anne; Anderson, Kevin M.; Plitt, Mark; Martin, Alex] NIMH, Sect Cognit Neuropsychol, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA.
RP Barnes, KA (reprint author), Baylor Coll Med, One Baylor Plaza,Rm T115,MS BCM295, Houston, TX 77030 USA.
EM kelly.barnes@bcm.edu
FU National Institute of Mental Health, Division of Intramural Research
Programs [ZIA MH-002588-23]
FX This work was supported by the National Institute of Mental Health,
Division of Intramural Research Programs, project number ZIA
MH-002588-23.
NR 40
TC 2
Z9 2
U1 1
U2 5
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-3077
EI 1522-1598
J9 J NEUROPHYSIOL
JI J. Neurophysiol.
PD OCT 15
PY 2014
VL 112
IS 8
BP 1838
EP 1848
DI 10.1152/jn.00909.2013
PG 11
WC Neurosciences; Physiology
SC Neurosciences & Neurology; Physiology
GA AR0BI
UT WOS:000343228000004
PM 25031254
ER
PT J
AU Root, DH
Mejias-Aponte, CA
Qi, J
Morales, M
AF Root, David H.
Mejias-Aponte, Carlos A.
Qi, Jia
Morales, Marisela
TI Role of Glutamatergic Projections from Ventral Tegmental Area to Lateral
Habenula in Aversive Conditioning
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
DE addiction; aversion; dopamine; reward; VGluT2
ID MIDBRAIN DOPAMINE NEURONS; REWARD; ACTIVATION; RESPONSES; STIMULI;
SIGNALS; INPUT
AB The ventral tegmental area (VTA) plays roles in both reward and aversion. The participation of VTA in diverse behaviors likely reflects its heterogeneous neuronal phenotypes and circuits. Recent findings indicate that VTA GABAergic neurons that coexpress tyrosine hydroxylase (TH) projecting to lateral habenula (LHb) play a role in reward. In addition to these mesohabenular TH-GABAergic neurons, the VTA has many neurons expressing vesicular glutamate transporter 2 (VGluT2) that also project to LHb. To determine the behavioral role of mesohabenular VGluT2 neurons, we targeted channelrhodopsin2 to VTA VGluT2 neurons of VGluT2::Cre mice. These mice were tested in an apparatus where moving into one chamber stimulated VTA VGluT2 projections within the LHb, and exiting the chamber inactivated the stimulation. We found that mice spent significantly less time in the chamber where VGluT2 mesohabenular fiber stimulation occurred. Mice that received injections of mixed AMPA and NMDA glutamate receptor antagonists in LHb were unresponsive to VGluT2-mesohabenular fiber stimulation, demonstrating the participation of LHb glutamate receptors in mesohabenular stimulation-elicited aversion. In the absence of light stimulation, mice showed a conditioned place aversion to the chamber that was previously associated with VGluT2-mesohabenular fiber stimulation. We conclude that there is a glutamatergic signal from VTA VGluT2-mesohabenular neurons that plays a role in aversion by activating LHb glutamatergic receptors.
C1 [Root, David H.; Mejias-Aponte, Carlos A.; Qi, Jia; Morales, Marisela] Natl Inst Drug Abuse, Integrat Neurosci Res Branch, Neuronal Networks Sect, Baltimore, MD 21224 USA.
RP Morales, M (reprint author), Natl Inst Drug Abuse, Integrat Neurosci Res Branch, Neuronal Networks Sect, 251 Bayview Blvd,Suite 200, Baltimore, MD 21224 USA.
EM mmorales@intra.nida.nih.gov
OI Root, David/0000-0002-1927-2175
FU Intramural Research Program of the National Institute on Drug Abuse
FX This work was supported by the Intramural Research Program of the
National Institute on Drug Abuse. We thank Kyle E. Ireton for technical
assistance.
NR 25
TC 38
Z9 38
U1 0
U2 5
PU SOC NEUROSCIENCE
PI WASHINGTON
PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA
SN 0270-6474
J9 J NEUROSCI
JI J. Neurosci.
PD OCT 15
PY 2014
VL 34
IS 42
BP 13906
EP 13910
DI 10.1523/JNEUROSCI.2029-14.2014
PG 5
WC Neurosciences
SC Neurosciences & Neurology
GA AQ9DJ
UT WOS:000343142800006
PM 25319687
ER
PT J
AU Wu, EL
Cheng, X
Jo, S
Rui, H
Song, KC
Davila-Contreras, EM
Qi, YF
Lee, JM
Monje-Galvan, V
Venable, RM
Klauda, JB
Im, W
AF Wu, Emilia L.
Cheng, Xi
Jo, Sunhwan
Rui, Huan
Song, Kevin C.
Davila-Contreras, Eder M.
Qi, Yifei
Lee, Jumin
Monje-Galvan, Viviana
Venable, Richard M.
Klauda, Jeffery B.
Im, Wonpil
TI CHARMM-GUI Membrane Builder Toward Realistic Biological Membrane
Simulations
SO JOURNAL OF COMPUTATIONAL CHEMISTRY
LA English
DT Article
DE cardiolipin; phosphoinositides; sphingolipids; lipid penetration
detection
ID MOLECULAR-DYNAMICS SIMULATIONS; ESCHERICHIA-COLI; USER-INTERFACE; LIPID
CHAIN; FORCE-FIELD; PROTEIN; BILAYERS; DOMAINS; PHOSPHOINOSITIDES;
SPHINGOLIPIDS
AB CHARMM-GUI Membrane Builder, http://www.charmm-gui.org/input/membrane, is a web-based user interface designed to interactively build all-atom protein/membrane or membrane-only systems for molecular dynamics simulations through an automated optimized process. In this work, we describe the new features and major improvements in Membrane Builder that allow users to robustly build realistic biological membrane systems, including (1) addition of new lipid types, such as phosphoinositides, cardiolipin (CL), sphingolipids, bacterial lipids, and ergosterol, yielding more than 180 lipid types, (2) enhanced building procedure for lipid packing around protein, (3) reliable algorithm to detect lipid tail penetration to ring structures and protein surface, (4) distance-based algorithm for faster initial ion displacement, (5) CHARMM inputs for P-21 image transformation, and (6) NAMD equilibration and production inputs. The robustness of these new features is illustrated by building and simulating a membrane model of the polar and septal regions of E. coli membrane, which contains five lipid types: CL lipids with two types of acyl chains and phosphatidylethanolamine lipids with three types of acyl chains. It is our hope that CHARMM-GUI Membrane Builder becomes a useful tool for simulation studies to better understand the structure and dynamics of proteins and lipids in realistic biological membrane environments. (C) 2014 Wiley Periodicals, Inc.
C1 [Wu, Emilia L.; Cheng, Xi; Jo, Sunhwan; Rui, Huan; Song, Kevin C.; Davila-Contreras, Eder M.; Qi, Yifei; Lee, Jumin; Im, Wonpil] Univ Kansas, Dept Mol Biosci, Lawrence, KS 66047 USA.
[Wu, Emilia L.; Cheng, Xi; Jo, Sunhwan; Rui, Huan; Song, Kevin C.; Davila-Contreras, Eder M.; Qi, Yifei; Lee, Jumin; Im, Wonpil] Univ Kansas, Ctr Bioinformat, Lawrence, KS 66047 USA.
[Monje-Galvan, Viviana; Klauda, Jeffery B.] Univ Maryland, Dept Chem & Biomol Engn, College Pk, MD 20742 USA.
[Venable, Richard M.] NHLBI, Lab Computat Biol, NIH, Bethesda, MD 20892 USA.
RP Wu, EL (reprint author), Univ Kansas, Dept Mol Biosci, Lawrence, KS 66047 USA.
EM jbklauda@umd.edu; wonpil@ku.edu
FU NSF [MCB-1157677, ABI-1145987, DBI-1145652, MCB-1149187]; NIH
[U54GM087519]; XSEDE [MCB070009]
FX Contract grant sponsor: NSF (W.I.); contract grant numbers: MCB-1157677;
ABI-1145987; Contract grant sponsor: NIH (W.I.); contract grant number:
U54GM087519; Contract grant sponsor: XSEDE (W.I.); contract grant
number: MCB070009; Contract grant sponsor: NSF (J.B.K.); contract grant
numbers: DBI-1145652; MCB-1149187
NR 65
TC 125
Z9 125
U1 7
U2 48
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0192-8651
EI 1096-987X
J9 J COMPUT CHEM
JI J. Comput. Chem.
PD OCT 15
PY 2014
VL 35
IS 27
BP 1997
EP 2004
DI 10.1002/jcc.23702
PG 8
WC Chemistry, Multidisciplinary
SC Chemistry
GA AQ4EZ
UT WOS:000342747400006
PM 25130509
ER
PT J
AU Harunaga, JS
Doyle, AD
Yamada, KM
AF Harunaga, Jill S.
Doyle, Andrew D.
Yamada, Kenneth M.
TI Local and global dynamics of the basement membrane during branching
morphogenesis require protease activity and actomyosin contractility
SO DEVELOPMENTAL BIOLOGY
LA English
DT Article
DE Basement membrane; Matrix dynamics; Branching morphogenesis; Proteases;
Myosin II
ID EPITHELIAL-MESENCHYMAL INTERFACE; EMBRYONIC MOUSE LUNG;
EXTRACELLULAR-MATRIX; SUBMANDIBULAR-GLAND; BASAL LAMINA; IN-VIVO;
COLLAGEN-IV; CELL; ELONGATION; CONTACTS
AB Many epithelial tissues expand rapidly during embryonic development while remaining surrounded by a basement membrane. Remodeling of the basement membrane is assumed to occur during branching morphogenesis to accommodate epithelial growth, but how such remodeling occurs is not yet clear. We report that the basement membrane is highly dynamic during branching of the salivary gland, exhibiting both local and global remodeling. At the tip of the epithelial end bud, the basement membrane becomes perforated by hundreds of well-defined microscopic holes at regions of rapid expansion. Locally, this results in a distensible, mesh-like basement membrane for controlled epithelial. expansion while maintaining tissue integrity Globally, the basement membrane translocates rearward as a whole, accumulating around the forming secondary ducts, helping to stabilize them during branching. Both local and global dynamics of the basement membrane require protease and myosin II activity. Our findings suggest that the basement membrane is rendered distensible by proteolytic degradation to allow it to be moved and remodeled by cells through actomyosin contractility to support branching morphogenesis. Published by Elsevier Inc.
C1 [Harunaga, Jill S.; Doyle, Andrew D.; Yamada, Kenneth M.] Natl Inst Dent & Craniofacial Res, Cell Biol Sect, Lab Cell & Dev Biol, NIH, Bethesda, MD 20892 USA.
RP Yamada, KM (reprint author), Natl Inst Dent & Craniofacial Res, Cell Biol Sect, Lab Cell & Dev Biol, NIH, 30 Convent Dr,Bldg 30,Room 403, Bethesda, MD 20892 USA.
EM kenneth.yamada@nih.gov
FU Intramural Research Program of the NIH, NIDCR
FX We are grateful to the Adelstein laboratory for the GFP-myosin II
knock-in mice. We also thank members of the Yamada laboratory for advice
and W. Daley, B. DuChez and M. Hoffman for critical reading of the
manuscript. This work was supported by the Intramural Research Program
of the NIH, NIDCR.
NR 37
TC 18
Z9 18
U1 1
U2 10
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 OCT 15
PY 2014
VL 394
IS 2
BP 197
EP 205
DI 10.1016/j.ydbio.2014.08.014
PG 9
WC Developmental Biology
SC Developmental Biology
GA AP9JF
UT WOS:000342395400002
PM 25158168
ER
PT J
AU Corsini, E
Luebke, RW
Germolec, DR
DeWitt, JC
AF Corsini, Emanuela
Luebke, Robert W.
Germolec, Dori R.
DeWitt, Jamie C.
TI Perfluorinated compounds: Emerging POPs with potential immunotoxicity
SO TOXICOLOGY LETTERS
LA English
DT Article
DE Perfluorinated compounds; Immunosuppression; PPAR-alpha receptor;
Cytokine; Vaccination
ID ACTIVATED RECEPTOR-ALPHA; PERFLUOROOCTANOIC ACID PFOA; B P65 SUBUNIT;
PEROXISOME PROLIFERATOR; AMMONIUM PERFLUOROOCTANOATE; HUMORAL IMMUNITY;
POLYFLUOROALKYL COMPOUNDS; PRENATAL EXPOSURE; DIETARY EXPOSURE;
PRODUCTION PLANT
AB Perfluorinated compounds (PFCs) have been recognized as an important class of environmental contaminants commonly detected in blood samples of both wildlife and humans. These compounds have been in use for more than 60 years as surface treatment chemicals, polymerization aids, and surfactants. They possess a strong carbon-fluorine bond, which leads to their environmental persistence. There is evidence from both epidemiology and laboratory studies that PFCs may be immunotoxic, affecting both cell-mediated and humoral immunity. Reported effects of PFCs include decreased spleen and thymus weights and cellularity, reduced specific antibody production, reduced survival after influenza infection, and altered cytokine production. Immunosuppression is a critical effect associated with exposure to PFCs, as it has been reported to reduce antibody responses to vaccination in children. Mounting evidence suggests that immunotoxicity in experimental animals can occur at serum concentrations below, within, or just above the reported range for highly exposed humans and wildlife. Considering bioaccumulation and exposure to multiple PFCs, the risk of immunotoxicity for humans and wildlife cannot be discounted. This review will discuss current and recently published work exploring the immunomodulatory effects of PFCs in experimental animals and humans. (C) 2014 Elsevier Ireland Ltd. All rights reserved.
C1 [Corsini, Emanuela] Univ Milan, Toxicol Lab, Dept Pharmacol & Biomol Sci, I-20133 Milan, Italy.
[Luebke, Robert W.] US EPA, Off Res & Dev, Natl Hlth & Environm Effects Res Lab, Res Triangle Pk, NC 27711 USA.
[Germolec, Dori R.] NIEHS, Natl Toxicol Program, NIH, Res Triangle Pk, NC USA.
[DeWitt, Jamie C.] E Carolina Univ, Brody Sch Med, Dept Pharmacol & Toxicol, Greenville, NC USA.
RP Corsini, E (reprint author), Univ Milan, Toxicol Lab, DiSFeB, Via Balzaretti 9, I-20133 Milan, Italy.
EM emanuela.corsini@unimi.it
OI DeWitt, Jamie/0000-0002-0440-4059
FU Intramural NIH HHS [Z99 ES999999]
NR 81
TC 22
Z9 25
U1 8
U2 73
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 OCT 15
PY 2014
VL 230
IS 2
BP 263
EP 270
DI 10.1016/j.toxlet.2014.01.038
PG 8
WC Toxicology
SC Toxicology
GA AP2CV
UT WOS:000341881000019
PM 24503008
ER
PT J
AU McLain, AC
Sundaram, R
Thoma, M
Louis, GMB
AF McLain, Alexander C.
Sundaram, Rajeshwari
Thoma, Marie
Louis, Germaine M. Buck
TI Semiparametric modeling of grouped current duration data with
preferential reporting
SO STATISTICS IN MEDICINE
LA English
DT Article
DE backwards recurrence times; current duration; digit preference; grouped
survival data; proportional hazards model
ID TIME-TO-PREGNANCY; DIGIT PREFERENCE; BIOLOGICAL FERTILITY;
REGRESSION-MODELS; SURVIVAL ANALYSIS; HUMAN FECUNDITY; UNITED-STATES;
FECUNDABILITY; INFERTILITY; LIFE
AB Current duration data arise in cross-sectional studies from questions on the length of time from an initiating event to the time of interview. For example, in the National Survey on Family Growth, women who were considered at risk for pregnancy were asked (i) 'Are you currently attempting pregnancy?' and (ii) 'If yes, how many months have you been attempting to get pregnant?' The responses to (ii), referred to as the current durations, are length-biased because women with longer durations are more likely to answer yes to question (i) and therefore be included in the sample. Previous methods to analyze such data include continuous time nonparametric and parametric approaches. In this article, we propose a semiparametric Cox model and a piecewise constant baseline model (used to account for digit preference) to analyze grouped current duration data. We discuss and investigate through simulation studies, the robustness properties of the proposed methods when digit preference is present. Lastly, we present an analysis of the current duration data resulting from the 2002 National Survey on Family Growth. Published 2014. This article is a U.S. Government work and is in the public domain in the USA.
C1 [McLain, Alexander C.] Univ S Carolina, Dept Epidemiol & Biostat, Columbia, SC 29208 USA.
[Sundaram, Rajeshwari; Thoma, Marie; Louis, Germaine M. Buck] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Intramural Populat Hlth Res, Rockville, MD 20852 USA.
RP McLain, AC (reprint author), Univ S Carolina, Dept Epidemiol & Biostat, 915 Greene St, Columbia, SC 29208 USA.
EM mclaina@mailbox.sc.edu
OI McLain, Alexander/0000-0002-5475-0670; Sundaram,
Rajeshwari/0000-0002-6918-5002; Buck Louis, Germaine/0000-0002-1774-4490
FU NICHD Intramural Research Program
FX This research was supported in part by the NICHD Intramural Research
Program (Louis and Sundaram).
NR 42
TC 3
Z9 3
U1 2
U2 8
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 OCT 15
PY 2014
VL 33
IS 23
BP 3961
EP 3972
DI 10.1002/sim.6216
PG 12
WC Mathematical & Computational Biology; Public, Environmental &
Occupational Health; Medical Informatics; Medicine, Research &
Experimental; Statistics & Probability
SC Mathematical & Computational Biology; Public, Environmental &
Occupational Health; Medical Informatics; Research & Experimental
Medicine; Mathematics
GA AP1JI
UT WOS:000341824700001
PM 24862959
ER
PT J
AU Kim, HJ
Luo, J
Kim, J
Chen, HS
Feuer, EJ
AF Kim, Hyune-Ju
Luo, Jun
Kim, Jeankyung
Chen, Huann-Sheng
Feuer, Eric J.
TI Clustering of trend data using joinpoint regression models
SO STATISTICS IN MEDICINE
LA English
DT Article
DE joinpoint regression; clustering; permutation test; Bayes information
criterion; minimum distance worth detecting
ID SEGMENTED LINE REGRESSION; PROSTATE-CANCER; SERIES
AB In this paper, we propose methods to cluster groups of two-dimensional data whose mean functions are piecewise linear into several clusters with common characteristics such as the same slopes. To fit segmented line regression models with common features for each possible cluster, we use a restricted least squaresmethod. In implementing the restricted least squares method, we estimate the maximum number of segments in each cluster by using both the permutation test method and the Bayes information criterion method and then propose to use the Bayes information criterion to determine the number of clusters. For a more effective implementation of the clustering algorithm, we propose a measure of the minimum distance worth detecting and illustrate its use in two examples. We summarize simulation results to study properties of the proposed methods and also prove the consistency of the cluster grouping estimated with a given number of clusters. The presentation and examples in this paper focus on the segmented line regression model with the ordered values of the independent variable, which has been the model of interest in cancer trend analysis, but the proposed method can be applied to a general model with design points either ordered or unordered. Copyright (C) 2014 John Wiley & Sons, Ltd.
C1 [Kim, Hyune-Ju] Syracuse Univ, Dept Math, Syracuse, NY 13244 USA.
[Luo, Jun] Informat Management Serv Inc, Calverton, MD 20705 USA.
[Kim, Jeankyung] Inha Univ, Dept Stat, Inchon 402751, South Korea.
[Chen, Huann-Sheng; Feuer, Eric J.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
RP Kim, HJ (reprint author), Syracuse Univ, Dept Math, Syracuse, NY 13244 USA.
EM hjkim@syr.edu
FU NIH [HHSN261201000509P, HHSN261200900681P]; Inha University
FX H-J. Kim's research was partially supported by NIH Contracts
HHSN261201000509P and HHSN261200900681P. J. Kim's research was supported
by a research grant from Inha University.
NR 14
TC 3
Z9 3
U1 0
U2 5
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 OCT 15
PY 2014
VL 33
IS 23
BP 4087
EP 4103
DI 10.1002/sim.6221
PG 17
WC Mathematical & Computational Biology; Public, Environmental &
Occupational Health; Medical Informatics; Medicine, Research &
Experimental; Statistics & Probability
SC Mathematical & Computational Biology; Public, Environmental &
Occupational Health; Medical Informatics; Research & Experimental
Medicine; Mathematics
GA AP1JI
UT WOS:000341824700010
PM 24895073
ER
PT J
AU Baker, SG
AF Baker, Stuart G.
TI Biomarker evaluation in randomized trials: addressing different research
questions
SO STATISTICS IN MEDICINE
LA English
DT Letter
ID CANCER
C1 NCI, Biometry Res Grp, Bethesda, MD 20892 USA.
RP Baker, SG (reprint author), NCI, Biometry Res Grp, Bethesda, MD 20892 USA.
EM sb16i@nih.gov
FU Intramural NIH HHS [Z99 CA999999]
NR 5
TC 1
Z9 1
U1 0
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 OCT 15
PY 2014
VL 33
IS 23
BP 4139
EP 4140
DI 10.1002/sim.6202
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 AP1JI
UT WOS:000341824700014
PM 25196226
ER
PT J
AU Dutra, SJ
Reeves, EJ
Mauss, IB
Gruber, J
AF Dutra, Sunny J.
Reeves, Elizabeth J.
Mauss, Iris B.
Gruber, June
TI Boiling at a different degree: An investigation of trait and state anger
in remitted bipolar I disorder
SO JOURNAL OF AFFECTIVE DISORDERS
LA English
DT Article
DE Anger; Emotion; Bipolar disorder
ID APPROACH SYSTEM BAS; SPECTRUM DISORDERS; POSITIVE EMOTIONS; MANIA SCALE;
DYSREGULATION; RELIABILITY; PREVALENCE; PROVOCATION; COMORBIDITY;
RESPONSES
AB Background: Elevated anger is a prominent clinical feature of bipolar disorder (BD). However, it is unclear whether this feature is characterized by elevated trait anger (i.e., how much anger one experiences in general) and/or state anger (i.e., how much anger one experiences when provoked), how stable anger elevations are (i.e., whether they appear during remission), and whether they have prognostic significance.
Methods: The present study assessed trait anger as well as state anger during a neutral baseline and a validated laboratory anger provocation among adults with remitted bipolar l disorder (BD; n=27) and healthy controls (CTL; n=29). To examine prognostic significance, we assessed manic and depressive symptom severity one year later in a subsample of BD participants (n=18).
Results: Results revealed greater trait anger as well as state anger experience at baseline for the BD compared to the CTL group. No group differences emerged in anger during the provocation. Anger did not predict symptom severity, but greater positive emotion during the provocation predicted mania (but not depression) symptom severity.
Limitations: We utilized a relatively high functioning sample of remitted BD patients. Future studies should include BD patients with current mood episodes and more diverse functioning, to ensure generalizability of our results.
Conclusions: These findings suggest that BD is characterized by elevated trait and baseline state anger, but not greater responding to anger provocation. Persistently elevated anger may represent a marker of BD, and context inappropriate positive emotion experience during anger provocation may constitute a vulnerability factor for mania severity. (C) 2014 Elsevier B.V. All rights reserved.
C1 [Dutra, Sunny J.; Gruber, June] Yale Univ, Dept Psychol, New Haven, CT 06520 USA.
[Reeves, Elizabeth J.] NIMH, Emot & Dev Branch, Baltimore, MD USA.
[Mauss, Iris B.] Univ Calif Berkeley, Dept Psychol, Berkeley, CA 94720 USA.
RP Gruber, J (reprint author), Yale Univ, Dept Psychol, POB 208205, New Haven, CT 06520 USA.
EM june.gruber@yale.edu
OI Gruber, Jens/0000-0003-4474-1217
NR 38
TC 3
Z9 3
U1 1
U2 7
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0165-0327
EI 1573-2517
J9 J AFFECT DISORDERS
JI J. Affect. Disord.
PD OCT 15
PY 2014
VL 168
BP 37
EP 43
DI 10.1016/j.jad.2014.06.044
PG 7
WC Clinical Neurology; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA AO6SZ
UT WOS:000341483100006
PM 25036007
ER
PT J
AU Benson, BE
Willis, MW
Ketter, TA
Speer, A
Kimbrell, TA
Herscovitch, P
George, MS
Post, RM
AF Benson, Brenda E.
Willis, Mark W.
Ketter, Terence A.
Speer, Andrew
Kimbrell, Tim A.
Herscovitch, Peter
George, Mark S.
Post, Robert M.
TI Differential abnormalities of functional connectivity of the amygdala
and hippocampus in unipolar and bipolar affective disorders
SO JOURNAL OF AFFECTIVE DISORDERS
LA English
DT Article
DE Neuroimaging; Mood disorders; Amygdala; Hippocampus; Functional
connectivity; Metabolism
ID MAJOR DEPRESSIVE DISORDER; MEDIAL PREFRONTAL CORTEX; CEREBRAL METABOLIC
ASSOCIATIVITY; TEMPORAL-LOBE STRUCTURES; MAGNETIC-RESONANCE; MOOD
DISORDERS; GLUCOSE-UTILIZATION; ALTERED INTERCORRELATIONS;
NEUROCOGNITIVE IMPAIRMENT; MACACA-FASCICULARIS
AB Objective: The amygdala and hippocampus - two structures intimately associated with mood and cognition - have been reported to exhibit altered neural activity or volume in affective disorders. We hypothesized the amygdala and hippocampus would show altered and differential patterns of connectivity in patients with bipolar (Bps) and unipolar (Ups) disorder compared to healthy volunteers.
Method: Thirty BPs, 34 UPs, and 66 healthy volunteers were imaged using F-18-fluorodeoxyglucose and positron emission tomography while performing an auditory continuous performance task (CPT). Normalized mean activity of the amygdala and hippocampus was correlated with the rest of the brain.
Results: In BPs, the amygdalae displayed exaggerated positive metabolic correlations with prefrontal and ventral striatal areas, while the hippocampus showed a paucity of normal inter-relations compared to controls. In contrast, in UPs the amygdala was significantly negatively correlated with prefrontal and anterior cingulate cortex, while the hippocampus was significantly more positively correlated to these same prefrontal areas.
Conclusions: During a simple cognitive task, the functional connectivity of the amygdala and hippocampus, regions usually associated with emotion and memory regulation, was substantially different in affective illness compared to healthy controls whether or not there were baseline abnormalities in these areas. These striking differences in functional connectivity of amygdala and hippocampus should be further explored in ill and well states and using more specific emotion and cognitive evocative tasks. Published by Elsevier B.V.
C1 [Benson, Brenda E.; Speer, Andrew] NIMH, NIH, Bethesda, MD 20892 USA.
[Willis, Mark W.] Uniformed Serv, Bethesda, MD USA.
[Ketter, Terence A.] Stanford Univ, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA.
[Kimbrell, Tim A.] Vet Affairs Med Ctr, Little Rock, AR USA.
[Herscovitch, Peter] NIH, Positron Emiss Tomog Dept, Bethesda, MD 20892 USA.
[George, Mark S.] Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA.
[Post, Robert M.] NIMH, Biol Psychiat Branch, NIH, Bethesda, MD 20892 USA.
[Post, Robert M.] Bipolar Collaborat Network, Bethesda, MD USA.
RP Benson, BE (reprint author), NIMH, NIH, US Dept HHS, Bldg 10 Rm B1D43D,10 Ctr Dr, Bethesda, MD 20892 USA.
EM bbenson@mail.nih.gov
FU NIMH, NIH, DHHS; Henry M. Jackson Foundation for the Advancement of
Military Medicine
FX This work was supported by the intramural program of the NIMH, NIH,
DHHS. The work of Mark Willis was supported by Ted and Vada Stanley of
the Stanley Foundation. Mark Willis also received salary support front
the Henry M. Jackson Foundation for the Advancement of Military
Medicine. Funding sources had no further role in study design, in the
collection, analysis and interpretation of data, in the writing of this
manuscript, and in the decision to submit the paper for publication.
NR 118
TC 4
Z9 4
U1 8
U2 24
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0165-0327
EI 1573-2517
J9 J AFFECT DISORDERS
JI J. Affect. Disord.
PD OCT 15
PY 2014
VL 168
BP 243
EP 253
DI 10.1016/j.jad.2014.05.045
PG 11
WC Clinical Neurology; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA AO6SZ
UT WOS:000341483100033
PM 25069080
ER
PT J
AU Wentzensen, N
Bakkum-Gamez, JN
Killian, K
Sampson, J
Guido, R
Glass, A
Adams, L
Luhn, P
Brinton, LA
Rush, B
d'Ambrosio, L
Gunja, M
Yang, HP
Garcia-Closas, M
Lacey, JV
Lissowska, J
Podratz, K
Meltzer, P
Shridhar, V
Sherman, ME
AF Wentzensen, Nicolas
Bakkum-Gamez, Jamie N.
Killian, Keith
Sampson, Joshua
Guido, Richard
Glass, Andrew
Adams, Lisa
Luhn, Patricia
Brinton, Louise A.
Rush, Brenda
d'Ambrosio, Lori
Gunja, Munira
Yang, Hannah P.
Garcia-Closas, Montserrat
Lacey, James V., Jr.
Lissowska, Jolanta
Podratz, Karl
Meltzer, Paul
Shridhar, Viji
Sherman, Mark E.
TI Discovery and validation of methylation markers for endometrial cancer
SO INTERNATIONAL JOURNAL OF CANCER
LA English
DT Article
DE endometrial cancer; methylation; biomarker; early detection; vaginal
bleeding
ID DNA METHYLATION; RISK-FACTORS; TAO BRUSH; HYPERPLASIA; CARCINOMA; WOMEN;
DIAGNOSIS; MANAGEMENT; EXPRESSION; PLAN
AB The prognosis of endometrial cancer is strongly associated with stage at diagnosis, suggesting that early detection may reduce mortality. Women who are diagnosed with endometrial carcinoma often have a lengthy history of vaginal bleeding, which offers an opportunity for early diagnosis and curative treatment. We performed DNA methylation profiling on population-based endometrial cancers to identify early detection biomarkers and replicated top candidates in two independent studies. We compared DNA methylation values of 1,500 probes representing 807 genes in 148 population-based endometrial carcinoma samples and 23 benign endometrial tissues. Markers were replicated in another set of 69 carcinomas and 40 benign tissues profiled on the same platform. Further replication was conducted in The Cancer Genome Atlas and in prospectively collected endometrial brushings from women with and without endometrial carcinomas. We identified 114 CpG sites showing methylation differences with p values of <= 10(-7) between endometrial carcinoma and normal endometrium. Eight genes (ADCYAP1, ASCL2, HS3ST2, HTR1B, MME, NPY and SOX1) were selected for further replication. Age-adjusted odds ratios for endometrial cancer ranged from 3.44 (95%-CI: 1.33-8.91) for ASCL2 to 18.61 (95%-CI: 5.50-62.97) for HTR1B. An area under the curve (AUC) of 0.93 was achieved for discriminating carcinoma from benign endometrium. Replication in The Cancer Genome Atlas and in endometrial brushings from an independent study confirmed the candidate markers. This study demonstrates that methylation markers may be used to evaluate women with abnormal vaginal bleeding to distinguish women with endometrial carcinoma from the majority of women without malignancy.
C1 [Wentzensen, Nicolas; Sampson, Joshua; Luhn, Patricia; Brinton, Louise A.; Gunja, Munira; Yang, Hannah P.; Sherman, Mark E.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Bakkum-Gamez, Jamie N.; Podratz, Karl; Shridhar, Viji] Mayo Clin, Dept Obstet & Gynecol, Rochester, MN USA.
[Killian, Keith; Adams, Lisa; Meltzer, Paul] NCI, Genet Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Guido, Richard; d'Ambrosio, Lori] UPMC Syst, Magee Womens Hosp, Dept Obstet & Gynecol, Pittsburgh, PA USA.
[Glass, Andrew; Rush, Brenda] Kaiser Permanente Northwest, Div Res, Portland, OR USA.
[Garcia-Closas, Montserrat] Inst Canc Res, Div Genet & Epidemiol, Sutton, Surrey, England.
[Lacey, James V., Jr.] City Hope Natl Med Ctr, Canc Control & Populat Sci Program, Duarte, CA USA.
[Lissowska, Jolanta] M Sklodowska Curie Mem Canc Ctr, Warsaw, Poland.
[Lissowska, Jolanta] Inst Oncol, Warsaw, Poland.
RP Wentzensen, N (reprint author), NCI, Div Canc Epidemiol & Genet, 9609 Med Ctr Dr,Room 7-E114, Bethesda, MD 20892 USA.
EM wentzenn@mail.nih.gov
RI Garcia-Closas, Montserrat /F-3871-2015; Brinton, Louise/G-7486-2015
OI Garcia-Closas, Montserrat /0000-0003-1033-2650; Brinton,
Louise/0000-0003-3853-8562
FU Intramural Research Program of the National Cancer Institute at the
National Institutes of Health
FX Grant sponsor: Intramural Research Program of the National Cancer
Institute at the National Institutes of Health
NR 37
TC 13
Z9 14
U1 1
U2 20
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 OCT 15
PY 2014
VL 135
IS 8
BP 1860
EP 1868
DI 10.1002/ijc.28843
PG 9
WC Oncology
SC Oncology
GA AN3YF
UT WOS:000340524100013
PM 24623538
ER
PT J
AU Xi, ZR
Yunusova, Y
van Blitterswijk, M
Dib, S
Ghani, M
Moreno, D
Sato, C
Liang, Y
Singleton, A
Robertson, J
Rademakers, R
Zinman, L
Rogaeva, E
AF Xi, Zhengrui
Yunusova, Yana
van Blitterswijk, Marka
Dib, Samar
Ghani, Mahdi
Moreno, Danielle
Sato, Christine
Liang, Yan
Singleton, Andrew
Robertson, Janice
Rademakers, Rosa
Zinman, Lorne
Rogaeva, Ekaterina
TI IDENTICAL TWINS WITH THE C9ORF72 REPEAT EXPANSION ARE DISCORDANT FOR ALS
SO NEUROLOGY
LA English
DT Editorial Material
ID HEXANUCLEOTIDE REPEAT; FTD
C1 [Xi, Zhengrui; Dib, Samar; Ghani, Mahdi; Moreno, Danielle; Sato, Christine; Liang, Yan; Robertson, Janice; Rogaeva, Ekaterina] Univ Toronto, Tanz Ctr Res Neurodegenerat Dis, Toronto, ON, Canada.
[Zinman, Lorne; Rogaeva, Ekaterina] Univ Toronto, Div Neurol, Toronto, ON, Canada.
[Yunusova, Yana; Zinman, Lorne] Sunnybrook Hlth Sci Ctr, Toronto, ON M4N 3M5, Canada.
[van Blitterswijk, Marka; Rademakers, Rosa] Mayo Clin, Jacksonville, FL 32224 USA.
[Singleton, Andrew] NIA, Neurogenet Lab, Bethesda, MD 20892 USA.
RP Rogaeva, E (reprint author), Univ Toronto, Tanz Ctr Res Neurodegenerat Dis, Toronto, ON, Canada.
EM Lorne.Zinman@sunnybrook.ca; ekaterina.rogaeva@utoronto.ca
RI Singleton, Andrew/C-3010-2009; van Blitterswijk, Marka/H-7274-2012;
Yunusova, Yana/E-3428-2010
OI van Blitterswijk, Marka/0000-0002-3054-7053; Yunusova,
Yana/0000-0002-2353-2275
FU NIA NIH HHS [AG000958-11, P50 AG016574, R01 AG026251, Z01 AG000958, ZO1
AG000958-11]; NINDS NIH HHS [R01 NS080882, P50 NS072187, R01 NS065782,
R01 NS080882-02]
NR 7
TC 14
Z9 14
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0028-3878
EI 1526-632X
J9 NEUROLOGY
JI Neurology
PD OCT 14
PY 2014
VL 83
IS 16
BP 1476
EP 1478
PG 3
WC Clinical Neurology
SC Neurosciences & Neurology
GA AT3RD
UT WOS:000344850500019
PM 25209579
ER
PT J
AU Clermont, PL
Sun, L
Crea, F
Thu, KL
Zhang, A
Parolia, A
Lam, WL
Helgason, CD
AF Clermont, P-L
Sun, L.
Crea, F.
Thu, K. L.
Zhang, A.
Parolia, A.
Lam, W. L.
Helgason, C. D.
TI Genotranscriptomic meta-analysis of the Polycomb gene CBX2 in human
cancers: initial evidence of an oncogenic role
SO BRITISH JOURNAL OF CANCER
LA English
DT Article
DE CBX2; polycomb; metastasis; prognosis; expression; breast; prostate;
lung; meta-analysis
ID METHYLATED HISTONE H3; EMBRYONIC STEM-CELLS; PROSTATE-CANCER; GROUP
PROTEIN; TUMOR-SUPPRESSOR; INTRATUMOR HETEROGENEITY; DNA
HYPERMETHYLATION; INK4A/ARF LOCUS; BREAST-CANCER; EXPRESSION
AB Background: Polycomb group (PcG) proteins are histone modifiers known to transcriptionally silence key tumour suppressor genes in multiple human cancers. The chromobox proteins (CBX2, 4, 6, 7, and 8) are critical components of PcG-mediated repression. Four of them have been associated with tumour biology, but the role of CBX2 in cancer remains largely uncharacterised.
Methods: Addressing this issue, we conducted a comprehensive and unbiased genotranscriptomic meta-analysis of CBX2 in human cancers using the COSMIC and Oncomine databases.
Results: We discovered changes in gene expression that are suggestive of a widespread oncogenic role for CBX2. Our genetic analysis of 8013 tumours spanning 29 tissue types revealed no inactivating chromosomal aberrations and only 40 point mutations at the CBX2 locus. In contrast, the overall rate of CBX2 amplification averaged 10% in all combined neoplasms but exceeded 30% in ovarian, breast, and lung tumours. In addition, transcriptomic analyses revealed a strong tendency for increased CBX2 mRNA levels in many cancers compared with normal tissues, independently of CDKN2A/B silencing. Furthermore, CBX2 upregulation and amplification significantly correlated with metastatic progression and lower overall survival in many cancer types, particularly those of the breast.
Conclusions: Overall, we report that the molecular profile of CBX2 is suggestive of an oncogenic role. As CBX2 has never been studied in human neoplasms, our results provide the rationale to further investigate the function of CBX2 in the context of cancer cells.
C1 [Clermont, P-L; Crea, F.; Zhang, A.; Parolia, A.; Helgason, C. D.] British Columbia Canc Res Ctr, Dept Expt Therapeut, Vancouver, BC V5Z 1L3, Canada.
[Clermont, P-L] Univ British Columbia, Fac Med, Interdisciplinary Oncol Program, Vancouver, BC V5Z 1L3, Canada.
[Sun, L.] NCI, Mouse Canc Genet Program, NIH, Ft Detrick, MD 21702 USA.
[Crea, F.; Helgason, C. D.] Univ British Columbia, Dept Surg, Vancouver, BC V5Z 1M9, Canada.
[Thu, K. L.; Lam, W. L.] British Columbia Canc Res Ctr, Dept Integrat Oncol, Genet Unit, Vancouver, BC V5Z 1L3, Canada.
[Parolia, A.] Univ British Columbia, Dept Microbiol & Immunol, Honours Biotechnol Program, Vancouver, BC V6T 1Z3, Canada.
RP Helgason, CD (reprint author), British Columbia Canc Res Ctr, Dept Expt Therapeut, 675 West 10th Ave, Vancouver, BC V5Z 1L3, Canada.
EM chelgaso@bccrc.ca
RI Crea, Francesco /I-8383-2015; Sun, Lei/J-9943-2015;
OI Crea, Francesco/0000-0002-4903-2973
FU Canadian Cancer Society Research Institute [701097]; Kruger Graduate
Fellowship
FX This work was supported by Canadian Cancer Society Research Institute
grant number 701097 (CDH) and a Kruger Graduate Fellowship (PLC).
NR 61
TC 10
Z9 10
U1 0
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 OCT 14
PY 2014
VL 111
IS 8
BP 1663
EP 1672
DI 10.1038/bjc.2014.474
PG 10
WC Oncology
SC Oncology
GA AR9YE
UT WOS:000343932600022
PM 25225902
ER
PT J
AU Inoue, AH
Serpeloni, M
Hiraiwa, PM
Yamada-Ogatta, SF
Muniz, JRC
Motta, MCM
Vidal, NM
Goldenberg, S
Avila, AR
AF Inoue, Alexandre Haruo
Serpeloni, Mariana
Hiraiwa, Priscila Mazzocchi
Yamada-Ogatta, Sueli Fumie
Carvalho Muniz, Joao Renato
Machado Motta, Maria Cristina
Vidal, Newton Medeiros
Goldenberg, Samuel
Avila, Andrea Rodrigues
TI Identification of a Novel Nucleocytoplasmic Shuttling RNA Helicase of
Trypanosomes
SO PLOS ONE
LA English
DT Article
ID NUCLEAR-PORE COMPLEX; INDUCIBLE EXPRESSION SYSTEM; EXON JUNCTION
COMPLEX; MESSENGER-RNA; EXPORT RECEPTOR; BINDING PROTEINS;
HIGH-THROUGHPUT; CRUZI; GENE; TRANSPORT
AB Gene expression in trypanosomes is controlled mostly by post-transcriptional pathways. Little is known about the components of mRNA nucleocytoplasmic export routes in these parasites. Comparative genomics has shown that the mRNA transport pathway is the least conserved pathway among eukaryotes. Nonetheless, we identified a RNA helicase (Hel45) that is conserved across eukaryotes and similar to shuttling proteins involved in mRNA export. We used in silico analysis to predict the structure of Trypanosoma cruzi Hel45, including the N-terminal domain and the C-terminal domain, and our findings suggest that this RNA helicase can form complexes with mRNA. Hel45 was present in both nucleus and cytoplasm. Electron microscopy showed that Hel45 is clustered close to the cytoplasmic side of nuclear pore complexes, and is also present in the nucleus where it is associated with peripheral compact chromatin. Deletion of a predicted Nuclear Export Signal motif led to the accumulation of Hel45 Delta NES in the nucleus, indicating that Hel45 shuttles between the nucleus and the cytoplasm. This transport was dependent on active transcription but did not depend on the exportin Crm1. Knockdown of Mex67 in T. brucei caused the nuclear accumulation of the T. brucei ortholog of Hel45. Indeed, Hel45 is present in mRNA ribonucleoprotein complexes that are not associated with polysomes. It is still necessary to confirm the precise function of Hel45. However, this RNA helicase is associated with mRNA metabolism and its nucleocytoplasmic shuttling is dependent on an mRNA export route involving Mex67 receptor.
C1 [Inoue, Alexandre Haruo; Serpeloni, Mariana; Hiraiwa, Priscila Mazzocchi; Vidal, Newton Medeiros; Goldenberg, Samuel; Avila, Andrea Rodrigues] Fiocruz MS, Inst Carlos Chagas, Curitiba, Parana, Brazil.
[Serpeloni, Mariana] Univ Fed Parana, Dept Biol Celular & Mol, BR-80060000 Curitiba, Parana, Brazil.
[Yamada-Ogatta, Sueli Fumie] Univ Estadual Londrina, Dept Microbiol, Londrina, Brazil.
[Carvalho Muniz, Joao Renato] Univ Sao Paulo, Inst Fis Sao Carlos, Sao Carlos, SP, Brazil.
[Machado Motta, Maria Cristina] Univ Fed Rio de Janeiro, Inst Biofis Carlos Chagas Filho, Dept Biol Celular & Parasitol, BR-21941 Rio De Janeiro, Brazil.
[Vidal, Newton Medeiros] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA.
RP Avila, AR (reprint author), Fiocruz MS, Inst Carlos Chagas, Curitiba, Parana, Brazil.
EM aravila@fiocruz.br
RI GOLDENBERG, SAMUEL/B-4116-2009; Sao Carlos Institute of Physics,
IFSC/USP/M-2664-2016
OI GOLDENBERG, SAMUEL/0000-0002-4892-163X;
FU Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq);
Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES);
Fundacao Oswaldo Cruz (PAPES- FIOCRUZ Program); Fundacao Araucaria-PR
FX Funding was provided by Conselho Nacional de Desenvolvimento Cientifico
e Tecnologico (CNPq), Coordenacao de Aperfeicoamento de Pessoal de Nivel
Superior (CAPES), Fundacao Oswaldo Cruz (PAPES- FIOCRUZ Program) and
Fundacao Araucaria-PR. The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 63
TC 3
Z9 3
U1 0
U2 3
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD OCT 14
PY 2014
VL 9
IS 10
AR e109521
DI 10.1371/journal.pone.0109521
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AR5ZW
UT WOS:000343662500047
PM 25313564
ER
PT J
AU Liu, T
Sae-Ueng, U
Li, D
Lander, GC
Zuo, XB
Jonsson, B
Rau, D
Shefer, I
Evilevitch, A
AF Liu, Ting
Sae-Ueng, Udom
Li, Dong
Lander, Gabriel C.
Zuo, Xiaobing
Jonsson, Bengt
Rau, Donald
Shefer, Ivetta
Evilevitch, Alex
TI Solid-to-fluid-like DNA transition in viruses facilitates infection
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE DNA fluidity; DNA ejection; intracapsid DNA transition; AFM; isothermal
titration calorimetry
ID PHAGE-LAMBDA; IN-VITRO; PHASE-TRANSITIONS; BACTERIOPHAGE; EJECTION;
PRESSURE; DYNAMICS; GENOME; FORCES; DEPENDENCE
AB Releasing the packaged viral DNA into the host cell is an essential process to initiate viral infection. In many double-stranded DNA bacterial viruses and herpesviruses, the tightly packaged genome is hexagonally ordered and stressed in the protein shell, called the capsid. DNA condensed in this state inside viral capsids has been shown to be trapped in a glassy state, with restricted molecular motion in vitro. This limited intracapsid DNA mobility is caused by the sliding friction between closely packaged DNA strands, as a result of the repulsive interactions between the negative charges on the DNA helices. It had been unclear how this rigid crystalline structure of the viral genome rapidly ejects from the capsid, reaching rates of 60,000 bp/s. Through a combination of single-molecule and bulk techniques, we determined how the structure and energy of the encapsidated DNA in phage lambda regulates the mobility required for its ejection. Our data show that packaged lambda-DNA undergoes a solid-to-fluid-like disordering transition as a function of temperature, resulting locally in less densely packed DNA, reducing DNA-DNA repulsions. This process leads to a significant increase in genome mobility or fluidity, which facilitates genome release at temperatures close to that of viral infection (37 degrees C), suggesting a remarkable physical adaptation of bacterial viruses to the environment of Escherichia coli cells in a human host.
C1 [Liu, Ting; Sae-Ueng, Udom; Li, Dong; Shefer, Ivetta; Evilevitch, Alex] Carnegie Mellon Univ, Dept Phys, Pittsburgh, PA 15213 USA.
[Lander, Gabriel C.] Scripps Res Inst, Dept Integrat Struct & Computat Biol, La Jolla, CA 92037 USA.
[Zuo, Xiaobing] Argonne Natl Lab, Adv Photon Source, Xray Sci Div, Argonne, IL 60439 USA.
[Jonsson, Bengt] Lund Univ, Dept Biophys Chem, SE-22100 Lund, Sweden.
[Rau, Donald] NIH, Lab Phys & Struct Biol, Program Phys Biol, Bethesda, MD 20892 USA.
[Evilevitch, Alex] Lund Univ, Dept Biochem & Struct Biol, SE-22100 Lund, Sweden.
RP Evilevitch, A (reprint author), Carnegie Mellon Univ, Dept Phys, Pittsburgh, PA 15213 USA.
EM alexe@cmu.edu
RI Evilevitch, Alex/P-3103-2014; Li, Dong/D-9221-2015
OI Evilevitch, Alex/0000-0002-0245-9574; Li, Dong/0000-0002-5282-6918
FU US Department of Energy [DE-AC02-06CH11357]; National Institutes of
Health (NIH) [RR17573]; Swedish Research Council VR [622-2008-726];
National Science Foundation [CHE-1152770]; Intramural Research Program
of the National Institutes of Child Health and Human Development, NIH
FX We gratefully acknowledge Meerim Jeembaeva for helping in the early
development of the ITC assay, Yi Wang and Marcel Bruchez for help with
fluorescence measurements, Kaitlin Hamilton for help with plaque assay
analysis, John Johnson for help with cryo-EM imaging, Xiangyun Qiu for
advice on SAXS analysis, James Shaw for support with AFM measurements,
and Michael Widom for fruitful discussions. We also thank Abigail
Templeton for proofreading and helpful advice during preparation of the
manuscript. The SAXS experiments were performed at beamline 12ID-B of
the APS at Argonne National Laboratory. We acknowledge the Advanced
Photon Source, which is an Office of Science User Facility operated by
Argonne National Laboratory for the US Department of Energy under
Contract DE-AC02-06CH11357. Electron microscopic imaging and
reconstruction were conducted at the National Resource for Automated
Molecular Microscopy, which is supported by the National Institutes of
Health (NIH) through the National Center for Research Resources P41
program (Grant RR17573). This work was supported by Swedish Research
Council VR Grant 622-2008-726 (to A.E.) and National Science Foundation
Grant CHE-1152770 (to A.E.). This work was partially supported by the
Intramural Research Program of the National Institutes of Child Health
and Human Development, NIH.
NR 44
TC 12
Z9 12
U1 3
U2 30
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 OCT 14
PY 2014
VL 111
IS 41
BP 14675
EP 14680
DI 10.1073/pnas.1321637111
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AQ6KW
UT WOS:000342922000028
PM 25271319
ER
PT J
AU Das, S
Li, JX
Holland, SJ
Iyer, LM
Hirano, M
Schorpp, M
Aravind, L
Cooper, MD
Boehm, T
AF Das, Sabyasachi
Li, Jianxu
Holland, Stephen J.
Iyer, Lakshminarayan M.
Hirano, Masayuki
Schorpp, Michael
Aravind, L.
Cooper, Max D.
Boehm, Thomas
TI Genomic donor cassette sharing during VLRA and VLRC assembly in jawless
vertebrates
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE adaptive immunity; molecular evolution; selection; agnatha
ID VARIABLE LYMPHOCYTE-RECEPTOR; ADAPTIVE IMMUNE-SYSTEMS; SEA LAMPREY;
EVOLUTION; LOCUS; GENE; HAGFISH; DIVERSIFICATION; IDENTIFICATION;
ORGANIZATION
AB Lampreys possess two T-like lymphocyte lineages that express either variable lymphocyte receptor (VLR) A or VLRC antigen receptors. VLRA(+) and VLRC+ lymphocytes share many similarities with the two principal T-cell lineages of jawed vertebrates expressing the alpha beta and gamma delta T-cell receptors (TCRs). During the assembly of VLR genes, several types of genomic cassettes are inserted, in step-wise fashion, into incomplete germ-line genes to generate the mature forms of antigen receptor genes. Unexpectedly, the structurally variable components of VLRA and VLRC receptors often possess partially identical sequences; this phenomenon of module sharing between these two VLR isotypes occurs in both lampreys and hagfishes. By contrast, VLRA and VLRC molecules typically do not share their building blocks with the structurally analogous VLRB receptors that are expressed by B-like lymphocytes. Our studies reveal that VLRA and VLRC germ-line genes are situated in close proximity to each other in the lamprey genome and indicate the interspersed arrangement of isotype-specific and shared genomic donor cassettes; these features may facilitate the shared cassette use. The genomic structure of the VLRA/VLRC locus in lampreys is reminiscent of the interspersed nature of the TCRA/TCRD locus in jawed vertebrates that also allows the sharing of some variable gene segments during the recombinatorial assembly of TCR genes.
C1 [Das, Sabyasachi; Li, Jianxu; Hirano, Masayuki; Cooper, Max D.] Emory Univ, Emory Vaccine Ctr, Atlanta, GA 30322 USA.
[Holland, Stephen J.; Schorpp, Michael; Boehm, Thomas] Max Planck Inst Immunobiol & Epigenet, Dept Dev Immunol, D-79108 Freiburg, Germany.
[Iyer, Lakshminarayan M.; Aravind, L.] NIH, Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA.
RP Cooper, MD (reprint author), Emory Univ, Emory Vaccine Ctr, Atlanta, GA 30322 USA.
EM mdcoope@emory.edu; boehm@immunbio.mpg.de
FU Max Planck Society; European Research Council (ERC) under the European
Union's Seventh Framework Programme, ERC [ERC-2012-AdG-323126];
Intramural Research Program of the National Institutes of Health (NIH),
Department of Health and Human Services; NIH [AI072435, GM100151];
Georgia Research Alliance
FX This work was supported by the Max Planck Society and has received
funding from the European Research Council (ERC) under the European
Union's Seventh Framework Programme (FP7/2007-2013), ERC Grant Agreement
No. ERC-2012-AdG-323126. Work by L.M.I. and L.A. is funded by the
Intramural Research Program of the National Institutes of Health (NIH),
Department of Health and Human Services. Work by S.D., J.L., M.H., and
M.D.C. was supported by NIH Grants AI072435 and GM100151 and the Georgia
Research Alliance.
NR 30
TC 2
Z9 2
U1 0
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 OCT 14
PY 2014
VL 111
IS 41
BP 14828
EP 14833
DI 10.1073/pnas.1415580111
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AQ6KW
UT WOS:000342922000054
PM 25228758
ER
PT J
AU Holland, SJ
Gao, MM
Hirano, M
Iyer, LM
Luo, M
Schorpp, M
Cooper, MD
Aravind, L
Mariuzza, RA
Boehm, T
AF Holland, Stephen J.
Gao, Mingming
Hirano, Masayuki
Iyer, Lakshminarayan M.
Luo, Ming
Schorpp, Michael
Cooper, Max D.
Aravind, L.
Mariuzza, Roy A.
Boehm, Thomas
TI Selection of the lamprey VLRC antigen receptor repertoire
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE adaptive immunity; molecular evolution; agnathans
ID VARIABLE LYMPHOCYTE RECEPTORS; ADAPTIVE IMMUNE-SYSTEM;
MONOCLONAL-ANTIBODIES; STRUCTURAL BASIS; SEA LAMPREY; RECOGNITION;
EVOLUTION; DIVERSITY; HAGFISH; DIVERSIFICATION
AB The alternative adaptive immune system of jawless vertebrates is based on different isotypes of variable lymphocyte receptors (VLRs) that are composed of leucine-rich repeats (LRRs) and expressed by distinct B- and T-like lymphocyte lineages. VLRB is expressed by B-like cells, whereas VLRA and VLRC are expressed by two T-like lineages that develop in the thymoid, a thymus-like structure in lamprey larvae. In each case, stepwise combinatorial insertions of different types of short donor LRR cassettes into incomplete germ-line genes are required to generate functional VLR gene assemblies. It is unknown, however, whether the diverse repertoires of VLRs that are expressed by peripheral blood lymphocytes are shaped by selection after their assembly. Here, we identify signatures of selection in the peripheral repertoire of VLRC antigen receptors that are clonally expressed by one of the T-like cell types in lampreys. Selection strongly favors VLRC molecules containing four internal variable leucine-rich repeat (LRRV) modules, although VLRC assemblies encoding five internal modules are initially equally frequent. In addition to the length selection, VLRC molecules in VLRC+ peripheral lymphocytes exhibit a distinct pattern of high entropy sites in the N-terminal LRR1 module, which is inserted next to the germ-line-encoded LRRNT module. This is evident in comparisons to VLRC gene assemblies found in the thymoid and to VLRC gene assemblies found in some VLRA(+) cells. Our findings are the first indication to our knowledge that selection operates on a VLR repertoire and provide a framework to establish the mechanism by which this selection occurs during development of the VLRC+ lymphocyte lineage.
C1 [Holland, Stephen J.; Schorpp, Michael; Boehm, Thomas] Max Planck Inst Immunobiol & Epigenet, Dept Dev Immunol, D-79108 Freiburg, Germany.
[Gao, Mingming; Luo, Ming; Mariuzza, Roy A.] Univ Maryland, Inst Biosci & Biotechnol Res, WM Keck Lab Struct Biol, Rockville, MD 20850 USA.
[Hirano, Masayuki; Cooper, Max D.] Emory Univ, Emory Vaccine Ctr, Atlanta, GA 30322 USA.
[Hirano, Masayuki; Cooper, Max D.] Emory Univ, Dept Pathol & Lab Med, Atlanta, GA 30322 USA.
[Iyer, Lakshminarayan M.; Aravind, L.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
[Luo, Ming] Univ Sci & Technol China, Hefei Natl Lab Phys Sci Microscale, Hefei 230027, Anhui, Peoples R China.
[Luo, Ming] Univ Sci & Technol China, Sch Life Sci, Hefei 230027, Anhui, Peoples R China.
[Mariuzza, Roy A.] Univ Maryland, Dept Cell Biol & Mol Genet, College Pk, MD 20742 USA.
RP Boehm, T (reprint author), Max Planck Inst Immunobiol & Epigenet, Dept Dev Immunol, D-79108 Freiburg, Germany.
EM mdcoope@emory.edu; mariuzza@ibbr.umd.edu; boehm@immunbio.mpg.de
FU Max Planck Society; European Research Council (ERC) under the European
Union's Seventh Framework Programme, ERC [ERC-2012-AdG-323126]; National
Institutes of Health (NIH) [AI036900]; China Scholarship Council;
Intramural Research Program of the NIH, Department of Health and Human
Services; NIH [AI072435, GM100151]
FX This work was supported by the Max Planck Society and has received
funding from the European Research Council (ERC) under the European
Union's Seventh Framework Programme (FP7/2007-2013), ERC Grant Agreement
ERC-2012-AdG-323126. R.A.M. was supported by National Institutes of
Health (NIH) Grant AI036900. M.L. was supported by the Joint Supervision
PhD Project of the China Scholarship Council. Work by L.M.I. and L.A. is
funded by the Intramural Research Program of the NIH, Department of
Health and Human Services, and that of M.D.C. and M.H. by NIH Grants
AI072435 and GM100151.
NR 31
TC 4
Z9 5
U1 0
U2 12
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 OCT 14
PY 2014
VL 111
IS 41
BP 14834
EP 14839
DI 10.1073/pnas.1415655111
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AQ6KW
UT WOS:000342922000055
PM 25228760
ER
PT J
AU Erliandri, I
Fu, HQ
Nakano, M
Kim, JH
Miga, KH
Liskovykh, M
Earnshaw, WC
Masumoto, H
Kouprina, N
Aladjem, MI
Larionov, V
AF Erliandri, Indri
Fu, Haiqing
Nakano, Megumi
Kim, Jung-Hyun
Miga, Karen H.
Liskovykh, Mikhail
Earnshaw, William C.
Masumoto, Hiroshi
Kouprina, Natalay
Aladjem, Mirit I.
Larionov, Vladimir
TI Replication of alpha-satellite DNA arrays in endogenous human
centromeric regions and in human artificial chromosome
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID CONDITIONAL CENTROMERE; HUMAN GENOME; CENP-B; HISTONE MODIFICATIONS;
GENE-EXPRESSION; HUMAN-CELLS; HELA-CELLS; CHROMATIN; SEQUENCE;
ORGANIZATION
AB In human chromosomes, centromeric regions comprise megabase-size arrays of 171 bp alpha-satellite DNA monomers. The large distances spanned by these arrays preclude their replication from external sites and imply that the repetitive monomers contain replication origins. However, replication within these arrays has not previously been profiled and the role of alpha-satellite DNA in initiation of DNA replication has not yet been demonstrated. Here, replication of alpha-satellite DNA in endogenous human centromeric regions and in de novo formed (H) under bar uman (A) under bar rtificial (C) under bar hromosome (HAC) was analyzed. We showed that alpha-satellite monomers could function as origins of DNA replication and that replication of alphoid arrays organized into centrochromatin occurred earlier than those organized into heterochromatin. The distribution of inter-origin distances within centromeric alphoid arrays was comparable to the distribution of inter-origin distances on randomly selected non-centromeric chromosomal regions. Depletion of CENP-B, a kinetochore protein that binds directly to a 17 bp CENP-B box motif common to alpha-satellite DNA, resulted in enrichment of alpha-satellite sequences for proteins of the ORC complex, suggesting that CENP-B may have a role in regulating the replication of centromeric regions. Mapping of replication initiation sites in the HAC revealed that replication preferentially initiated in transcriptionally active regions.
C1 [Erliandri, Indri; Fu, Haiqing; Kim, Jung-Hyun; Liskovykh, Mikhail; Kouprina, Natalay; Aladjem, Mirit I.; Larionov, Vladimir] NCI, Dev Therapeut Branch, NIH, Bethesda, MD 20892 USA.
[Nakano, Megumi; Masumoto, Hiroshi] Kazusa DNA Res Inst, Dept Frontier Res, Lab Cell Engn, Kisarazu, Chiba 2920818, Japan.
[Miga, Karen H.] Univ Calif Santa Cruz, Ctr Biomol Sci & Engn, Santa Cruz, CA 95064 USA.
[Earnshaw, William C.] Univ Edinburgh, Wellcome Trust Ctr Cell Biol, Edinburgh EH9 3JR, Midlothian, Scotland.
RP Kouprina, N (reprint author), NCI, Dev Therapeut Branch, NIH, Bethesda, MD 20892 USA.
EM kouprinn@mail.nih.gov
RI Aladjem, Mirit/G-2169-2010
OI Aladjem, Mirit/0000-0002-1875-3110
FU Intramural Research Program of the NIH; National Cancer Institute;
Center for Cancer Research, USA; Wellcome Trust Principal Research
Fellowship [073915]; Ministry of Education, Culture, Sports, Science and
Technology of Japan [23247030, 23114008]
FX Intramural Research Program of the NIH; National Cancer Institute;
Center for Cancer Research, USA (to V.L. and M.I.A.); Wellcome Trust
Principal Research Fellowship [073915] (to W.C.E.); Grand-in-Aid for
Scientific Research from Ministry of Education, Culture, Sports, Science
and Technology of Japan [23247030, 23114008 to H.M.].
NR 60
TC 5
Z9 5
U1 1
U2 11
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
EI 1362-4962
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD OCT 13
PY 2014
VL 42
IS 18
BP 11502
EP 11516
DI 10.1093/nar/gku835
PG 15
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA AY6PC
UT WOS:000347687100027
PM 25228468
ER
PT J
AU Renaud, G
LaFave, MC
Liang, J
Wolfsberg, TG
Burgess, SM
AF Renaud, Gabriel
LaFave, Matthew C.
Liang, Jin
Wolfsberg, Tyra G.
Burgess, Shawn M.
TI trieFinder: an efficient program for annotating Digital Gene Expression
(DGE) tags
SO BMC BIOINFORMATICS
LA English
DT Article
DE RNA-Seq; Transcriptional profiling; DGE; SAGE
ID HUMAN GENOME; ARRAYS; MEMORY
AB Background: Quantification of a transcriptional profile is a useful way to evaluate the activity of a cell at a given point in time. Although RNA-Seq has revolutionized transcriptional profiling, the costs of RNA-Seq are still significantly higher than microarrays, and often the depth of data delivered from RNA-Seq is in excess of what is needed for simple transcript quantification. Digital Gene Expression (DGE) is a cost-effective, sequence-based approach for simple transcript quantification: by sequencing one read per molecule of RNA, this technique can be used to efficiently count transcripts while obviating the need for transcript-length normalization and reducing the total numbers of reads necessary for accurate quantification. Here, we present trieFinder, a program specifically designed to rapidly map, parse, and annotate DGE tags of various lengths against cDNA and/ or genomic sequence databases.
Results: The trieFinder algorithm maps DGE tags in a two-step process. First, it scans FASTA files of RefSeq, UniGene, and genomic DNA sequences to create a database of all tags that can be derived from a predefined restriction site. Next, it compares the experimental DGE tags to this tag database, taking advantage of the fact that the tags are stored as a prefix tree, or " trie", which allows for linear-time searches for exact matches. DGE tags with mismatches are analyzed by recursive calls in the data structure. We find that, in terms of alignment speed, the mapping functionality of trieFinder compares favorably with Bowtie.
Conclusions: trieFinder can quickly provide the user an annotation of the DGE tags from three sources simultaneously, simplifying transcript quantification and novel transcript detection, delivering the data in a simple parsed format, obviating the need to post-process the alignment results. trieFinder is available at http://research.nhgri.nih.gov/software/trieFinder/.
C1 [Renaud, Gabriel] Max Planck Inst Evolutionary Anthropol, Dept Evolutionary Genet, D-04103 Leipzig, Saxony, Germany.
[Renaud, Gabriel; Wolfsberg, Tyra G.] NHGRI, Computat & Stat Genom Branch, Div Intramural Res, NIH, Bethesda, MD 20892 USA.
[LaFave, Matthew C.; Liang, Jin; Burgess, Shawn M.] NHGRI, Translat & Funct Genom Branch, Div Intramural Res, NIH, Bethesda, MD 20892 USA.
[Liang, Jin] Weil Inst Cell & Mol Biol, Dept Biol Stat & Computat Biol, Ithaca, NY 14853 USA.
RP Burgess, SM (reprint author), NHGRI, Translat & Funct Genom Branch, Div Intramural Res, NIH, Bethesda, MD 20892 USA.
EM burgess@mail.nih.gov
OI Burgess, Shawn/0000-0003-1147-0596; LaFave, Matthew/0000-0001-9165-041X
FU Intramural Research Program of the National Human Genome Research
Institute, National Institutes of Health; NSERC for a PGS Doctoral
scholarship
FX This research was supported by the Intramural Research Program of the
National Human Genome Research Institute, National Institutes of Health
(SB). GR acknowledges financial support from NSERC for a PGS Doctoral
scholarship.
NR 16
TC 1
Z9 1
U1 0
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 OCT 13
PY 2014
VL 15
AR 329
DI 10.1186/1471-2105-15-329
PG 6
WC Biochemical Research Methods; Biotechnology & Applied Microbiology;
Mathematical & Computational Biology
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Mathematical & Computational Biology
GA AT3EA
UT WOS:000344817700001
PM 25311246
ER
PT J
AU Fischer, RS
AF Fischer, Robert S.
TI Move your microvilli
SO JOURNAL OF CELL BIOLOGY
LA English
DT Editorial Material
ID MESENCHYMAL TRANSITION; ERM PROTEINS; CELLS; CORTEX; MORPHOGENESIS;
FILOPODIA; MEMBRANE; DRIVEN
AB Polarized epithelial cells create tightly packed arrays of microvilli in their apical membrane, but the fate of these microvilli is relatively unknown when epithelial cell polarity is lost during wound healing. In this issue, Klingner et al. (2014. J. Cell Biol. http://dx.doi.org/10.1083/jcb.201402037) show that, when epithelial cells become subconfluent, actomyosin contractions locally within the apical cortex cause their microvilli to become motile over the dorsal/apical surface. Their unexpected observations may have implications for epithelial responses in wound healing and disease.
C1 NHLBI, Cell Biol & Physiol Ctr, NIH, Bethesda, MD 20892 USA.
RP Fischer, RS (reprint author), NHLBI, Cell Biol & Physiol Ctr, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM fischerr2@nhlbi.nih.gov
FU Intramural NIH HHS
NR 22
TC 0
Z9 0
U1 0
U2 1
PU ROCKEFELLER UNIV PRESS
PI NEW YORK
PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA
SN 0021-9525
EI 1540-8140
J9 J CELL BIOL
JI J. Cell Biol.
PD OCT 13
PY 2014
VL 207
IS 1
BP 9
EP 11
DI 10.1083/jcb.201409059
PG 3
WC Cell Biology
SC Cell Biology
GA AQ9SB
UT WOS:000343194900004
PM 25313404
ER
PT J
AU Burke, MC
Li, FQ
Cyge, B
Arashiro, T
Brechbuhl, HM
Chen, XW
Siller, SS
Weiss, MA
O'Connell, CB
Love, D
Westlake, CJ
Reynolds, SD
Kuriyama, R
Takemaru, KI
AF Burke, Michael C.
Li, Feng-Qian
Cyge, Benjamin
Arashiro, Takeshi
Brechbuhl, Heather M.
Chen, Xingwang
Siller, Saul S.
Weiss, Matthew A.
O'Connell, Christopher B.
Love, Damon
Westlake, Christopher J.
Reynolds, Susan D.
Kuriyama, Ryoko
Takemaru, Ken-Ichi
TI Chibby promotes ciliary vesicle formation and basal body docking during
airway cell differentiation
SO JOURNAL OF CELL BIOLOGY
LA English
DT Article
ID INTRAFLAGELLAR TRANSPORT; EPITHELIAL-CELLS; MOTHER CENTRIOLE; TRANSITION
ZONE; PRIMARY CILIUM; CILIOGENESIS; PROTEIN; MEMBRANE; APPENDAGES;
COMPLEX
AB Airway multiciliated epithelial cells play crucial roles in the mucosal defense system, but their differentiation process remains poorly understood. Mice lacking the basal body component Chibby (Cby) exhibit impaired mucociliary transport caused by defective ciliogenesis, resulting in chronic airway infection. In this paper, using primary cultures of mouse tracheal epithelial cells, we show that Cby facilitates basal body docking to the apical cell membrane through proper formation of ciliary vesicles at the distal appendage during the early stages of ciliogenesis. Cby is recruited to the distal appendages of centrioles via physical interaction with the distal appendage protein CEP164. Cby then associates with the membrane trafficking machinery component Rabin8, a guanine nucleotide exchange factor for the small guanosine triphosphatase Rab8, to promote recruitment of Rab8 and efficient assembly of ciliary vesicles. Thus, our study identifies Cby as a key regulator of ciliary vesicle formation and basal body docking during the differentiation of airway ciliated cells.
C1 [Burke, Michael C.; Takemaru, Ken-Ichi] SUNY Stony Brook, Grad Program Genet, Stony Brook, NY 11794 USA.
[Burke, Michael C.; Siller, Saul S.; Takemaru, Ken-Ichi] SUNY Stony Brook, Med Scientist Training Program, Stony Brook, NY 11794 USA.
[Li, Feng-Qian; Cyge, Benjamin; Chen, Xingwang; Siller, Saul S.; Love, Damon; Takemaru, Ken-Ichi] SUNY Stony Brook, Grad Program Mol & Cellular Pharmacol, Stony Brook, NY 11794 USA.
[Li, Feng-Qian; Takemaru, Ken-Ichi] SUNY Stony Brook, Dept Pharmacol Sci, Stony Brook, NY 11794 USA.
[Arashiro, Takeshi; Kuriyama, Ryoko] Univ Minnesota, Dep Genet Cell Biol & Dev, Minneapolis, MN 55455 USA.
[Brechbuhl, Heather M.; Reynolds, Susan D.] Natl Jewish Heath, Dept Pediat, Div Cell Biol, Denver, CO 80206 USA.
[Weiss, Matthew A.; Westlake, Christopher J.] NCI, Lab Cell & Dev Signaling, Frederick, MD 21072 USA.
[O'Connell, Christopher B.] Nikon Instruments Inc, Melville, NY 11747 USA.
RP Takemaru, KI (reprint author), SUNY Stony Brook, Grad Program Genet, Stony Brook, NY 11794 USA.
EM ken-ichi.takemaru@stonybrook.edu
FU National Science Foundation [MCB1140033]; American Heart Association
[11GRNT7860023]; National Institutes of Health/National Heart, Lung, and
Blood Institute grant [R01HI107493]
FX This work was supported by a National Science Foundation grant
(MCB1140033) to R. Kuriyama, an American Heart Association Grant-in-Aid
(11GRNT7860023) to F.-Q. Li, and a National Institutes of
Health/National Heart, Lung, and Blood Institute grant (R01HI107493) to
K.-I. Takemaru.
NR 52
TC 14
Z9 14
U1 0
U2 4
PU ROCKEFELLER UNIV PRESS
PI NEW YORK
PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA
SN 0021-9525
EI 1540-8140
J9 J CELL BIOL
JI J. Cell Biol.
PD OCT 13
PY 2014
VL 207
IS 1
BP 123
EP 137
DI 10.1083/jcb.201406140
PG 15
WC Cell Biology
SC Cell Biology
GA AQ9SB
UT WOS:000343194900012
PM 25313408
ER
PT J
AU Houghton, LC
Cooper, GD
Booth, M
Chowdhury, OA
Troisi, R
Ziegler, RG
Katki, HA
Hoover, RN
Bentley, GR
AF Houghton, Lauren C.
Cooper, Gillian D.
Booth, Mark
Chowdhury, Osul A.
Troisi, Rebecca
Ziegler, Regina G.
Katki, Hormuzd A.
Hoover, Robert N.
Bentley, Gillian R.
TI Childhood Environment Influences Adrenarcheal Timing among
First-Generation Bangladeshi Migrant Girls to the UK
SO PLOS ONE
LA English
DT Article
ID ADRENAL ANDROGEN EXCRETION; FOR-GESTATIONAL-AGE; PREMATURE ADRENARCHE;
BIRTH-WEIGHT; BODY-MASS; PUBERTAL DEVELOPMENT; PRECOCIOUS PUBERTY;
NUTRITIONAL-STATUS; METABOLIC SYNDROME; UNITED-KINGDOM
AB Background: Adrenarche is a key early life event that marks middle childhood at approximately 7 years of age. Earlier work with British-Bangladeshi migrant women suggested that environmental conditions experienced before adrenarche influence adult reproductive function. We therefore investigated whether Bangladeshi children who migrate to the United Kingdom (UK) reach adrenarche earlier than non-migrants in Bangladesh or the United Kingdom.
Methods and Findings: Healthy girls, aged 5-16 years, were recruited from schools in Sylhet, Bangladesh and London, England comprising four groups: Sylhetis (n = 165), first-generation migrants to the United Kingdom (n = 42), second-generation girls (n = 162), and British girls of European origin (n = 50). Anthropometric measurements were collected together with questionnaire data for migration and socioeconomic characteristics. Saliva samples were assayed for dehydroepiandrosterone (DHEAS) using enzyme-linked immunosorbent assays. Multiple linear regressions tested for group differences in anthropometric and socioeconomic variables and DHEAS levels. Median ages at adrenarche (DHEAS>400 pg/ml) were estimated using Weibull regression models for parametric survival analysis. Hazard ratios for reaching adrenarche earlier and 95% confidence intervals (CI), both unadjusted and adjusted for anthropometric variables, were estimated from the survival analyses. First-generation migrants had a median age at adrenarche (5.3 years) that was significantly earlier than Sylheti (7.2), second-generation (7.4), and European (7.1) girls. In univariate analyses, first-generation girls reached adrenarche significantly earlier than Sylhetis [HR (CI): 2.8 (1.4-5.5]. In multivariate models, first generation girls still reached adrenarche earlier than Sylhetis after adjusting for height [HR(CI): 1.9 (0.9-4.1)] and weight [HR(CI): 1.7 (0.8-3.8)], but these results were attenuated.
Conclusions: We suggest that rapid catch-up growth experienced by first generation girls during early childhood may explain their advanced adrenarche. The environmental conditions leading to an earlier adrenarche, as well as the health implications of this early transition, merit further exploration.
C1 [Houghton, Lauren C.; Troisi, Rebecca; Ziegler, Regina G.; Katki, Hormuzd A.; Hoover, Robert N.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Houghton, Lauren C.; Cooper, Gillian D.; Bentley, Gillian R.] Univ Durham, Dept Anthropol, Durham, England.
[Houghton, Lauren C.; Cooper, Gillian D.; Bentley, Gillian R.] Univ Durham, Wolfson Res Inst Hlth & Wellbeing, Durham, England.
[Booth, Mark] Univ Durham, Sch Med Pharm & Hlth, Durham, England.
[Chowdhury, Osul A.] Sylhet MAG Osmani Med Coll, Sylhet, Bangladesh.
RP Houghton, LC (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
EM houghtonlc@mail.nih.gov
RI Booth, Mark/D-2266-2011; Katki, Hormuzd/B-4003-2015
OI Booth, Mark/0000-0002-5507-888X;
FU intramural division of the U.S. National Cancer Institute (NCI) at the
National Institutes of Health; Wellcome Trust
FX This work was supported by the intramural division of the U.S. National
Cancer Institute (NCI) at the National Institutes of Health and the
Wellcome Trust. Intramural investigators at the NCI designed and
assisted in the analysis of the study. The Wellcome Trust had no role in
study design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 84
TC 4
Z9 4
U1 0
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 OCT 13
PY 2014
VL 9
IS 10
AR e109200
DI 10.1371/journal.pone.0109200
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AQ9WZ
UT WOS:000343210300041
PM 25309977
ER
PT J
AU Scharrer, S
Presi, P
Hattendorf, J
Chitnis, N
Reist, M
Zinsstag, J
AF Schaerrer, Sara
Presi, Patrick
Hattendorf, Jan
Chitnis, Nakul
Reist, Martin
Zinsstag, Jakob
TI Demographic Model of the Swiss Cattle Population for the Years 2009-2011
Stratified by Gender, Age and Production Type
SO PLOS ONE
LA English
DT Article
ID RISK-BASED SURVEILLANCE; SWITZERLAND; MORTALITY
AB Demographic composition and dynamics of animal and human populations are important determinants for the transmission dynamics of infectious disease and for the effect of infectious disease or environmental disasters on productivity. In many circumstances, demographic data are not available or of poor quality. Since 1999 Switzerland has been recording cattle movements, births, deaths and slaughter in an animal movement database (AMD). The data present in the AMD offers the opportunity for analysing and understanding the dynamic of the Swiss cattle population. A dynamic population model can serve as a building block for future disease transmission models and help policy makers in developing strategies regarding animal health, animal welfare, livestock management and productivity. The Swiss cattle population was therefore modelled using a system of ordinary differential equations. The model was stratified by production type (dairy or beef), age and gender (male and female calves: 0-1 year, heifers and young bulls: 1-2 years, cows and bulls: older than 2 years). The simulation of the Swiss cattle population reflects the observed pattern accurately. Parameters were optimized on the basis of the goodness-of-fit (using the Powell algorithm). The fitted rates were compared with calculated rates from the AMD and differed only marginally. This gives confidence in the fitted rates of parameters that are not directly deductible from the AMD (e. g. the proportion of calves that are moved from the dairy system to fattening plants).
C1 [Schaerrer, Sara; Presi, Patrick] Univ Bern, Vet Publ Hlth Inst, Bern, Switzerland.
[Hattendorf, Jan; Chitnis, Nakul; Zinsstag, Jakob] Univ Basel, Swiss Trop & Publ Hlth Inst, Basel, Switzerland.
[Chitnis, Nakul] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Reist, Martin] Fed Food Safety & Vet Off, Bern, Switzerland.
RP Scharrer, S (reprint author), Univ Bern, Vet Publ Hlth Inst, Bern, Switzerland.
EM sara.schaerrer@vetsuisse.unibe.ch
RI Chitnis, Nakul/B-3105-2013; Zinsstag, Jakob/A-8317-2008; Hattendorf,
Jan/F-5371-2010
OI Zinsstag, Jakob/0000-0002-8899-6097; Hattendorf, Jan/0000-0002-1176-401X
FU Swiss Federal Veterinary Office
FX The study was funded as part of a PhD project by the Swiss Federal
Veterinary Office. The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 17
TC 4
Z9 4
U1 0
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 OCT 13
PY 2014
VL 9
IS 10
AR e109329
DI 10.1371/journal.pone.0109329
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AQ9WZ
UT WOS:000343210300047
PM 25310680
ER
PT J
AU Schuck, RN
Zha, WB
Edin, ML
Gruzdev, A
Vendrov, KC
Miller, TM
Xu, ZH
Lih, FB
DeGraff, LM
Tomer, KB
Jones, HM
Makowski, L
Huang, L
Poloyac, SM
Zeldin, DC
Lee, CR
AF Schuck, Robert N.
Zha, Weibin
Edin, Matthew L.
Gruzdev, Artiom
Vendrov, Kimberly C.
Miller, Tricia M.
Xu, Zhenghong
Lih, Fred B.
DeGraff, Laura M.
Tomer, Kenneth B.
Jones, H. Michael
Makowski, Liza
Huang, Leaf
Poloyac, Samuel M.
Zeldin, Darryl C.
Lee, Craig R.
TI The Cytochrome P450 Epoxygenase Pathway Regulates the Hepatic
Inflammatory Response in Fatty Liver Disease
SO PLOS ONE
LA English
DT Article
ID SOLUBLE EPOXIDE HYDROLASE; HYDRODYNAMICS-BASED TRANSFECTION; LARGE GENE
LISTS; NONALCOHOLIC STEATOHEPATITIS; ENDOTHELIAL EXPRESSION; EICOSANOID
METABOLISM; ARACHIDONIC-ACID; ATHEROGENIC DIET; MICE; MOUSE
AB Fatty liver disease is an emerging public health problem without effective therapies, and chronic hepatic inflammation is a key pathologic mediator in its progression. Cytochrome P450 (CYP) epoxygenases metabolize arachidonic acid to biologically active epoxyeicosatrienoic acids (EETs), which have potent anti-inflammatory effects. Although promoting the effects of EETs elicits anti-inflammatory and protective effects in the cardiovascular system, the contribution of CYP-derived EETs to the regulation of fatty liver disease-associated inflammation and injury is unknown. Using the atherogenic diet model of non-alcoholic fatty liver disease/non-alcoholic steatohepatitis (NAFLD/NASH), our studies demonstrated that induction of fatty liver disease significantly and preferentially suppresses hepatic CYP epoxygenase expression and activity, and both hepatic and circulating levels of EETs in mice. Furthermore, mice with targeted disruption of Ephx2 (the gene encoding soluble epoxide hydrolase) exhibited restored hepatic and circulating EET levels and a significantly attenuated induction of hepatic inflammation and injury. Collectively, these data suggest that suppression of hepatic CYP-mediated EET biosynthesis is an important pathological consequence of fatty liver disease-associated inflammation, and that the CYP epoxygenase pathway is a central regulator of the hepatic inflammatory response in NAFLD/NASH. Future studies investigating the utility of therapeutic strategies that promote the effects of CYP-derived EETs in NAFLD/NASH are warranted.
C1 [Schuck, Robert N.; Zha, Weibin; Vendrov, Kimberly C.; Lee, Craig R.] Univ N Carolina, Eshelman Sch Pharm, Div Pharmacotherapy & Expt Therapeut, Chapel Hill, NC 27515 USA.
[Edin, Matthew L.; Gruzdev, Artiom; Lih, Fred B.; DeGraff, Laura M.; Tomer, Kenneth B.; Zeldin, Darryl C.] NIEHS, Div Intramural Res, NIH, Res Triangle Pk, NC 27709 USA.
[Miller, Tricia M.; Poloyac, Samuel M.] Univ Pittsburgh, Sch Pharm, Dept Pharmaceut Sci, Pittsburgh, PA 15261 USA.
[Xu, Zhenghong; Huang, Leaf] Univ N Carolina, Eshelman Sch Pharm, Div Mol Pharmaceut, Chapel Hill, NC USA.
[Jones, H. Michael] Univ N Carolina, Sch Med, Dept Pathol & Lab Med, Chapel Hill, NC USA.
[Makowski, Liza] Univ N Carolina, Gillings Sch Global Publ Hlth, Dept Nutr, Chapel Hill, NC USA.
RP Lee, CR (reprint author), Univ N Carolina, Eshelman Sch Pharm, Div Pharmacotherapy & Expt Therapeut, Chapel Hill, NC 27515 USA.
EM craig_lee@unc.edu
OI Makowski, Liza/0000-0002-5337-8037; Edin, Matthew/0000-0002-7042-500X;
Lee, Craig/0000-0003-3595-5301
FU NIH/NIGMS [R01GM088199]; NIH/NHLBI [T32HL069768]; American Heart
Association [11PRE7240059]; NIH/NINDS [R01NS052315]; NIH/NCRR
[S10RR023461]; NIH/NIAAA [AA017376]; NIH/NIDDK [P30DK34987]; UNC
Nutrition Obesity Research Center [P30DK056350]; Intramural Research
Program of the NIH/NIEHS [Z01ES050167, Z01ES025034]
FX This publication was made possible by a grant from the NIH/NIGMS
(R01GM088199) to Dr. Lee, a predoctoral training program in Integrative
Vascular Biology supported by the NIH/NHLBI (T32HL069768) and a
predoctoral fellowship from the American Heart Association
(11PRE7240059) to Dr. Schuck, grants from the NIH/NINDS (R01NS052315)
and NIH/NCRR (S10RR023461) to Dr. Poloyac, NIH/NIAAA (AA017376) to Dr.
Makowski, NIH/NIDDK to the UNC Center for Gastrointestinal Biology and
Disease (P30DK34987) and UNC Nutrition Obesity Research Center
(P30DK056350), and funds from the Intramural Research Program of the
NIH/NIEHS to Dr. Tomer (Z01ES050167) and Dr. Zeldin (Z01ES025034). Its
contents are solely the responsibility of the authors and do not
necessarily represent the official views of the NIH. The funders had no
role in study design, data collection and analysis, decision to publish,
or preparation of the manuscript.
NR 44
TC 13
Z9 13
U1 0
U2 13
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD OCT 13
PY 2014
VL 9
IS 10
AR e110162
DI 10.1371/journal.pone.0110162
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AQ9WZ
UT WOS:000343210300093
PM 25310404
ER
PT J
AU Yeon, SI
Kim, JY
Yeon, DS
Abramowitz, J
Birnbaumer, L
Muallem, S
Lee, YH
AF Yeon, Soo-In
Kim, Joo Young
Yeon, Dong-Soo
Abramowitz, Joel
Birnbaumer, Lutz
Muallem, Shmuel
Lee, Young-Ho
TI Transient Receptor Potential Canonical Type 3 Channels Control the
Vascular Contractility of Mouse Mesenteric Arteries
SO PLOS ONE
LA English
DT Article
ID TRPC3 CHANNELS; CARDIOVASCULAR-DISEASE; CEREBRAL-ARTERIES;
ENDOTHELIAL-CELLS; BLOOD-PRESSURE; MYOGENIC TONE; ION CHANNELS;
RELAXATION; ACTIVATION; EXPRESSION
AB Transient receptor potential canonical type 3 (TRPC3) channels are non-selective cation channels and regulate intracellular Ca2+ concentration. We examined the role of TRPC3 channels in agonist-, membrane depolarization (high K+)-, and mechanical (pressure)-induced vasoconstriction and vasorelaxation in mouse mesenteric arteries. Vasoconstriction and vasorelaxation of endothelial cells intact mesenteric arteries were measured in TRPC3 wild-type (WT) and knockout (KO) mice. Calcium concentration ([Ca2+]) was measured in isolated arteries from TRPC3 WT and KO mice as well as in the mouse endothelial cell line bEnd.3. Nitric oxide (NO) production and nitrate/nitrite concentrations were also measured in TRPC3 WT and KO mice. Phenylephrine-induced vasoconstriction was reduced in TRPC3 KO mice when compared to that of WT mice, but neither high K+- nor pressure-induced vasoconstriction was altered in TRPC3 KO mice. Acetylcholine-induced vasorelaxation was inhibited in TRPC3 KO mice and by the selective TRPC3 blocker pyrazole-3. Acetylcholine blocked the phenylephrine-induced increase in Ca2+ ratio and then relaxation in TRPC3 WT mice but had little effect on those outcomes in KO mice. Acetylcholine evoked a Ca2+ increase in endothelial cells, which was inhibited by pyrazole-3. Acetylcholine induced increased NO release in TRPC3 WT mice, but not in KO mice. Acetylcholine also increased the nitrate/nitrite concentration in TRPC3 WT mice, but not in KO mice. The present study directly demonstrated that the TRPC3 channel is involved in agonist-induced vasoconstriction and plays important role in NO-mediated vasorelaxation of intact mesenteric arteries.
C1 [Yeon, Soo-In; Lee, Young-Ho] Yonsei Univ, Coll Med, Dept Physiol, Seoul, South Korea.
[Yeon, Soo-In; Kim, Joo Young; Lee, Young-Ho] Yonsei Univ, Coll Med, PLUS Project Med Sci BK21, Seoul, South Korea.
[Kim, Joo Young] Yonsei Univ, Coll Med, Dept Pharmacol, Seoul, South Korea.
[Yeon, Dong-Soo] Kwandong Univ, Coll Med, Dept Physiol, Kangnung, South Korea.
[Abramowitz, Joel; Birnbaumer, Lutz] NIEHS, Neurobiol Lab, Res Triangle Pk, NC 27709 USA.
[Muallem, Shmuel] Natl Inst Dent & Craniofacial Res, Epithelial Signaling & Transport Sect, Mol Physiol & Therapeut Branch, NIH, Bethesda, MD USA.
RP Lee, YH (reprint author), Yonsei Univ, Coll Med, Dept Physiol, Seoul, South Korea.
EM yhlee@yuhs.ac
RI Abramowitz, Joel/A-2620-2015
FU National Research Foundation of Korea (NRF) - Korean government (MEST)
[NRF-2011-0029459]; Intramural Research Program of the National
Institutes of Health (NIH) [Z0-ES101864]
FX This work was supported by a National Research Foundation of Korea (NRF)
grant funded by the Korean government (MEST) (No. NRF-2011-0029459) and
by the Intramural Research Program of the National Institutes of Health
(NIH) (project Z0-ES101864 to LB). The funders had no role in study
design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 43
TC 3
Z9 3
U1 1
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 OCT 13
PY 2014
VL 9
IS 10
AR e110413
DI 10.1371/journal.pone.0110413
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AQ9WZ
UT WOS:000343210300115
PM 25310225
ER
PT J
AU Grandaubert, J
Lowe, RGT
Soyer, JL
Schoch, CL
de Wouw, APV
Fudal, I
Robbertse, B
Lapalu, N
Links, MG
Ollivier, B
Linglin, J
Barbe, V
Mangenot, S
Cruaud, C
Borhan, H
Howlett, BJ
Balesdent, MH
Rouxel, T
AF Grandaubert, Jonathan
Lowe, Rohan G. T.
Soyer, Jessica L.
Schoch, Conrad L.
de Wouw, Angela P. Van
Fudal, Isabelle
Robbertse, Barbara
Lapalu, Nicolas
Links, Matthew G.
Ollivier, Benedicte
Linglin, Juliette
Barbe, Valerie
Mangenot, Sophie
Cruaud, Corinne
Borhan, Hossein
Howlett, Barbara J.
Balesdent, Marie-Helene
Rouxel, Thierry
TI Transposable element-assisted evolution and adaptation to host plant
within the Leptosphaeria maculans-Leptosphaeria biglobosa species
complex of fungal pathogens
SO BMC GENOMICS
LA English
DT Article
DE Comparative genomics; Fungal plant pathogen; Transposable elements;
Effector genes; Speciation; Adaptation to host
ID INDUCED POINT MUTATIONS; PHOMA STEM CANKER; OILSEED RAPE; HORIZONTAL
TRANSFER; MOLECULAR EVOLUTION; MAGNAPORTHE-GRISEA; EUKARYOTIC GENOMES;
FILAMENTOUS FUNGI; BLACKLEG FUNGUS; OPEN SOFTWARE
AB Background: Many plant-pathogenic fungi have a tendency towards genome size expansion, mostly driven by increasing content of transposable elements (TEs). Through comparative and evolutionary genomics, five members of the Leptosphaeria maculans-Leptosphaeria biglobosa species complex (class Dothideomycetes, order Pleosporales), having different host ranges and pathogenic abilities towards cruciferous plants, were studied to infer the role of TEs on genome shaping, speciation, and on the rise of better adapted pathogens.
Results: L. maculans 'brassicae', the most damaging species on oilseed rape, is the only member of the species complex to have a TE-invaded genome (32.5%) compared to the other members genomes (<4%). These TEs had an impact at the structural level by creating large TE-rich regions and are suspected to have been instrumental in chromosomal rearrangements possibly leading to speciation. TEs, associated with species-specific genes involved in disease process, also possibly had an incidence on evolution of pathogenicity by promoting translocations of effector genes to highly dynamic regions and thus tuning the regulation of effector gene expression in planta.
Conclusions: Invasion of L. maculans 'brassicae' genome by TEs followed by bursts of TE activity allowed this species to evolve and to better adapt to its host, making this genome species a peculiarity within its own species complex as well as in the Pleosporales lineage.
C1 [Grandaubert, Jonathan; Soyer, Jessica L.; Fudal, Isabelle; Ollivier, Benedicte; Linglin, Juliette; Balesdent, Marie-Helene; Rouxel, Thierry] INRA Bioger, UR1290, F-78850 Thiverval Grignon, France.
[Lowe, Rohan G. T.; de Wouw, Angela P. Van; Howlett, Barbara J.] Univ Melbourne, Sch Bot, Melbourne, Vic 3010, Australia.
[Schoch, Conrad L.; Robbertse, Barbara] Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20892 USA.
[Lapalu, Nicolas] INRA Bioger, URGI, F-78026 Versailles, France.
[Links, Matthew G.] Agr & Agri Food Canada, Saskatoon Res Ctr, Saskatoon, SK S7N OX2, Canada.
[Links, Matthew G.] Univ Saskatchewan, Dept Comp, Saskatoon, SK S7N 5C9, Canada.
[Barbe, Valerie; Mangenot, Sophie; Cruaud, Corinne] CEA DSV, GENOSCOPE, Ctr Natl Sequencage, Inst Genom, F-91057 Evry, France.
RP Rouxel, T (reprint author), INRA Bioger, UR1290, Ave Lucien Bretignieres,BP 01, F-78850 Thiverval Grignon, France.
EM rouxel@versailles.inra.fr
OI Borhan, Hossein/0000-0002-6377-9192
FU French agency Agence Nationale de la Recherche (ANR) ('Funglsochores')
[ANR-09-GENM-028]; French Technical Institute for oil crops, CETIOM
FX This work was funded by the French agency Agence Nationale de la
Recharche (ANR), contract ANR-09-GENM-028 ('Funglsochores') and by the
French Technical Institute for oil crops, CETIOM. CLS acknowledges the
Intramural Research Program of the NIH, National Library of Medicine. We
thank Joelle Amselem and Jonathan Kreplak (INRA URGI, Versailles) for
their help on genome annotation, and also sebastien Duplessis
(INRA/Universite de Lorraine, Champenoux, France), and Eva Stukenbrock
(MPI Marburg, Germany) for fruitful discussions.
NR 107
TC 31
Z9 31
U1 3
U2 42
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 OCT 12
PY 2014
VL 15
AR 891
DI 10.1186/1471-2164-15-891
PG 27
WC Biotechnology & Applied Microbiology; Genetics & Heredity
SC Biotechnology & Applied Microbiology; Genetics & Heredity
GA AS9ME
UT WOS:000344566000001
PM 25306241
ER
PT J
AU Jayson, GC
Kohn, EC
Kitchener, HC
Ledermann, JA
AF Jayson, Gordon C.
Kohn, Elise C.
Kitchener, Henry C.
Ledermann, Jonathan A.
TI Ovarian cancer
SO LANCET
LA English
DT Article
ID RANDOMIZED CONTROLLED-TRIAL; PHASE-III TRIAL; RECURRENT EPITHELIAL
OVARIAN; GYNECOLOGIC-ONCOLOGY-GROUP; PEGYLATED LIPOSOMAL DOXORUBICIN;
MOLECULAR-GENETIC-ANALYSIS; PLACEBO-CONTROLLED TRIAL; GRADE SEROUS
CARCINOMA; ADVANCED SOLID TUMORS; BRCA2 MUTATIONS
AB Epithelial ovarian cancer is the commonest cause of gynaecological cancer-associated death. The disease typically presents in postmenopausal women, with a few months of abdominal pain and distension. Most women have advanced disease (International Federation of Gynecology and Obstetrics [FIGO] stage III), for which the standard of care remains surgery and platinum-based cytotoxic chemotherapy. Although this treatment can be curative for most patients with early stage disease, most women with advanced disease will develop many episodes of recurrent disease with progressively shorter disease-free intervals. These episodes culminate in chemoresistance and ultimately bowel obstruction, the most frequent cause of death. For women whose disease continues to respond to platinum-based drugs, the disease can often be controlled for 5 years or more. Targeted treatments such as antiangiogenic drugs or poly (ADP-ribose) polymerase inhibitors off er potential for improved survival. The efficacy of screening, designed to detect the disease at an earlier and curable stage remains unproven, with key results expected in 2015.
C1 [Jayson, Gordon C.] Christie Hosp, Inst Canc Studies, Manchester M20 4BX, Lancs, England.
[Jayson, Gordon C.; Kitchener, Henry C.] Univ Manchester, Manchester, Lancs, England.
[Kohn, Elise C.] NCI, Ctr Canc Res, Bethesda, MD 20892 USA.
[Kitchener, Henry C.] St Marys Hosp, Inst Canc Studies, Manchester M13 0JH, Lancs, England.
[Ledermann, Jonathan A.] UCL, Inst Canc, London, England.
RP Jayson, GC (reprint author), Christie Hosp, Manchester M20 4BX, Lancs, England.
EM Gordon.Jayson@Manchester.ac.uk
RI Jayson, Gordon/O-8224-2015
OI Jayson, Gordon/0000-0002-8515-8944
FU Intramural Program of the Center for Cancer Research, National Cancer
Institute, National Institutes of Health, USA
FX The authors would like to thank Andrew Clamp for his review and comments
on the manuscript. ECK was supported by the Intramural Program of the
Center for Cancer Research, National Cancer Institute, National
Institutes of Health, USA. We also thank Richard Fitzmaurice for the
photographs in figure 1, and James O'Connor for the images in figure 4.
NR 132
TC 196
Z9 206
U1 12
U2 61
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0140-6736
EI 1474-547X
J9 LANCET
JI Lancet
PD OCT 11
PY 2014
VL 384
IS 9951
BP 1376
EP 1388
DI 10.1016/S0140-6736(13)62146-7
PG 13
WC Medicine, General & Internal
SC General & Internal Medicine
GA AQ7NH
UT WOS:000343004000028
PM 24767708
ER
PT J
AU Chowell, G
Nishiura, H
AF Chowell, Gerardo
Nishiura, Hiroshi
TI Transmission dynamics and control of Ebola virus disease (EVD): a review
SO BMC MEDICINE
LA English
DT Review
DE Ebola Virus Disease; Transmission model; Control interventions; Basic
reproduction number; West Africa; Incubation; Serial interval; Case
fatality ratio; Isolation; Behavior change
ID ACUTE RESPIRATORY SYNDROME; HEMORRHAGIC-FEVER OUTBREAKS; PANDEMIC
INFLUENZA; INFECTIOUS-DISEASE; SARS OUTBREAKS; RISK-FACTORS; HONG-KONG;
CONGO; UGANDA; STRATEGIES
AB The complex and unprecedented Ebola epidemic ongoing in West Africa has highlighted the need to review the epidemiological characteristics of Ebola Virus Disease (EVD) as well as our current understanding of the transmission dynamics and the effect of control interventions against Ebola transmission. Here we review key epidemiological data from past Ebola outbreaks and carry out a comparative review of mathematical models of the spread and control of Ebola in the context of past outbreaks and the ongoing epidemic in West Africa. We show that mathematical modeling offers useful insights into the risk of a major epidemic of EVD and the assessment of the impact of basic public health measures on disease spread. We also discuss the critical need to collect detailed epidemiological data in real-time during the course of an ongoing epidemic, carry out further studies to estimate the effectiveness of interventions during past outbreaks and the ongoing epidemic, and develop large-scale modeling studies to study the spread and control of viral hemorrhagic fevers in the context of the highly heterogeneous economic reality of African countries.
C1 [Chowell, Gerardo] Arizona State Univ, Sch Human Evolut & Social Change, Tempe, AZ 85004 USA.
[Chowell, Gerardo] NIH, Div Int Epidemiol & Populat Studies, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Nishiura, Hiroshi] Univ Tokyo, Grad Sch Med, Dept Global Hlth Policy, Bunkyo Ku, Tokyo 1100033, Japan.
RP Chowell, G (reprint author), Arizona State Univ, Sch Human Evolut & Social Change, Tempe, AZ 85004 USA.
EM gchowell@asu.edu
FU NSF, NSF-NIH-USDA Ecology and Evolution of Infectious Diseases program
[1414374]; UK Biotechnology and Biological Sciences Research Council
[BB/M008894/1]; NSF [1318788]; Japanese Society for the Promotion of
Science (JSPS) KAKENHI [26700028]; St Luke's Life Science Institute
Research Grant for Clinical Epidemiology Research; Commissioned Research
program of the Ministry of Health, Labour and Welfare, Japan
[H26-ShinkoJitsuyoka-General-016]
FX 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 grant 1318788. III: Small: Data Management for
Real-Time Data Driven Epidemic Spread Simulations, the Division of
International Epidemiology and Population Studies, The Fogarty
International Center, US National Institutes of Health, and the Visiting
Foreign Scholar program of the Heiwa Nakajima Foundation for supporting
a sabbatical research visit at the University of Tokyo. HN received
funding support from the Japanese Society for the Promotion of Science
(JSPS) KAKENHI Grant Number 26700028, St Luke's Life Science Institute
Research Grant for Clinical Epidemiology Research 2014 and the
Commissioned Research program of the Ministry of Health, Labour and
Welfare, Japan (H26-ShinkoJitsuyoka-General-016).
NR 97
TC 72
Z9 77
U1 10
U2 183
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1741-7015
J9 BMC MED
JI BMC Med.
PD OCT 10
PY 2014
VL 12
AR 196
DI 10.1186/s12916-014-0196-0
PG 16
WC Medicine, General & Internal
SC General & Internal Medicine
GA AT4GI
UT WOS:000344897400001
PM 25300956
ER
PT J
AU Inamori, K
Willer, T
Hara, Y
Venzke, D
Anderson, ME
Clarke, NF
Guicheney, P
Bonnemann, CG
Moore, SA
Campbell, KP
AF Inamori, Kei-ichiro
Willer, Tobias
Hara, Yuji
Venzke, David
Anderson, Mary E.
Clarke, Nigel F.
Guicheney, Pascale
Boennemann, Carsten G.
Moore, Steven A.
Campbell, Kevin P.
TI Endogenous Glucuronyltransferase Activity of LARGE or LARGE2 Required
for Functional Modification of alpha-Dystroglycan in Cells and Tissues
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID CONGENITAL MUSCULAR-DYSTROPHY; WALKER-WARBURG-SYNDROME; HUMAN LARGE
GENE; LAMININ-BINDING; ABNORMAL GLYCOSYLATION; LARGE FAMILY; MUTATIONS;
GLYCOSYLTRANSFERASES; EXPRESSION; ISPD
AB Mutations in the LARGE gene have been identified in congenital muscular dystrophy (CMD) patients with brain abnormalities. Both LARGE and its paralog, LARGE2 (also referred to as GYLTL1B) are bifunctional glycosyltransferases with xylosyltransferase (Xyl-T) and glucuronyltransferase (GlcA-T) activities, and are capable of forming polymers consisting of [-3Xyl-alpha 1,3GlcA beta 1-] repeats. LARGE-dependent modification of alpha-dystroglycan (alpha-DG) with these polysaccharides is essential for the ability of alpha-DG to act as a receptor for ligands in the extracellular matrix. Here we report on the endogenous enzymatic activities of LARGE and LARGE2 in mice and humans, using a newly developed assay for GlcA-T activity. We show that normal mouse and human cultured cells have endogenous LARGE GlcA-T, and that this activity is absent in cells from the Large(myd) (Large-deficient) mouse model of muscular dystrophy, as well as in cells from CMD patients with mutations in the LARGE gene. We also demonstrate that GlcA-T activity is significant in the brain, heart, and skeletal muscle of wild-type and Large2(-/-) mice, but negligible in the corresponding tissues of the Large(myd) mice. Notably, GlcA-T activity is substantial, though reduced, in the kidneys of both the Large(myd) and Large2(-/-) mice, consistent with the observation of alpha-DG/laminin binding in these contexts. This study is the first to test LARGE activity in samples as small as cryosections and, moreover, provides the first direct evidence that not only LARGE, but also LARGE2, is vital to effective functional modification of alpha-DG in vivo.
C1 [Inamori, Kei-ichiro; Willer, Tobias; Hara, Yuji; Venzke, David; Anderson, Mary E.; Campbell, Kevin P.] Univ Iowa, Howard Hughes Med Inst, Dept Mol Physiol & Biophys,Dept Internal Med, Roy J & Lucille A Carver Coll Med,Dept Neurol, Iowa City, IA 52242 USA.
[Inamori, Kei-ichiro] Tohoku Pharmaceut Univ, Inst Mol Biomembrane & Glycobiol, Div Glycopathol, Sendai, Miyagi 9818558, Japan.
[Clarke, Nigel F.] Univ Sydney, Childrens Hosp Westmead, Inst Neurosci & Muscle Res, Sydney, NSW 2006, Australia.
[Guicheney, Pascale] Fac Med Pierre & Marie Curie, INSERM, U1166, Inst Cardiometab & Nutr,ICAN, Paris, France.
[Guicheney, Pascale] Univ Paris 06, UMR S1166, Univ Sorbonne, Paris, France.
[Boennemann, Carsten G.] NINDS, Neurogenet Branch, NIH, Bethesda, MD 20892 USA.
[Moore, Steven A.] Univ Iowa, Dept Pathol, Roy J & Lucille A Carver Coll Med, Iowa City, IA 52242 USA.
RP Campbell, KP (reprint author), Univ Iowa, Howard Hughes Med Inst, Dept Mol Physiol & Biophys,Dept Internal Med, Roy J & Lucille A Carver Coll Med,Dept Neurol, Iowa City, IA 52242 USA.
EM kevin-campbell@uiowa.edu
FU Senator Paul D. Wellstone Muscular Dystrophy Cooperative Research Center
[1 U54 NS053672]; Muscular Dystrophy Association; American Recovery and
Reinvestment Act (ARRA) Go Grant [1 RC2 NS069521-01]
FX This work was supported in part by the Senator Paul D. Wellstone
Muscular Dystrophy Cooperative Research Center Grant (1 U54 NS053672, to
K. P. C., S. A. M., and T. W.), the Muscular Dystrophy Association, and
an American Recovery and Reinvestment Act (ARRA) Go Grant (1 RC2
NS069521-01, to K. P. C. and T. W.).
NR 48
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Z9 7
U1 0
U2 5
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
EI 1083-351X
J9 J BIOL CHEM
JI J. Biol. Chem.
PD OCT 10
PY 2014
VL 289
IS 41
BP 28138
EP 28148
DI 10.1074/jbc.M114.597831
PG 11
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA AR7NC
UT WOS:000343765400011
PM 25138275
ER
PT J
AU Molkov, YI
Shevtsova, NA
Park, C
Ben-Tal, A
Smith, JC
Rubin, JE
Rybak, IA
AF Molkov, Yaroslav I.
Shevtsova, Natalia A.
Park, Choongseok
Ben-Tal, Alona
Smith, Jeffrey C.
Rubin, Jonathan E.
Rybak, Ilya A.
TI A Closed-Loop Model of the Respiratory System: Focus on Hypercapnia and
Active Expiration
SO PLOS ONE
LA English
DT Article
ID MAMMALIAN BRAIN-STEM; FUNCTIONAL ARCHITECTURE; REFLEX PROLONGATION;
INTEGRATED MODEL; GAS-EXCHANGE; NEWBORN RAT; RHYTHM; PATTERN;
INSPIRATION; NEURONS
AB Breathing is a vital process providing the exchange of gases between the lungs and atmosphere. During quiet breathing, pumping air from the lungs is mostly performed by contraction of the diaphragm during inspiration, and muscle contraction during expiration does not play a significant role in ventilation. In contrast, during intense exercise or severe hypercapnia forced or active expiration occurs in which the abdominal "expiratory" muscles become actively involved in breathing. The mechanisms of this transition remain unknown. To study these mechanisms, we developed a computational model of the closed-loop respiratory system that describes the brainstem respiratory network controlling the pulmonary subsystem representing lung biomechanics and gas (O-2 and CO2) exchange and transport. The lung subsystem provides two types of feedback to the neural subsystem: a mechanical one from pulmonary stretch receptors and a chemical one from central chemoreceptors. The neural component of the model simulates the respiratory network that includes several interacting respiratory neuron types within the Botzinger and pre-Botzinger complexes, as well as the retrotrapezoid nucleus/parafacial respiratory group (RTN/pFRG) representing the central chemoreception module targeted by chemical feedback. The RTN/pFRG compartment contains an independent neural generator that is activated at an increased CO2 level and controls the abdominal motor output. The lung volume is controlled by two pumps, a major one driven by the diaphragm and an additional one activated by abdominal muscles and involved in active expiration. The model represents the first attempt to model the transition from quiet breathing to breathing with active expiration. The model suggests that the closed-loop respiratory control system switches to active expiration via a quantal acceleration of expiratory activity, when increases in breathing rate and phrenic amplitude no longer provide sufficient ventilation. The model can be used for simulation of closed-loop control of breathing under different conditions including respiratory disorders.
C1 [Molkov, Yaroslav I.] Purdue Univ, Indiana Univ, Dept Math Sci, Indianapolis, IN USA.
[Shevtsova, Natalia A.; Rybak, Ilya A.] Drexel Univ, Coll Med, Dept Neurobiol & Anat, Philadelphia, PA 19104 USA.
[Park, Choongseok; Rubin, Jonathan E.] Univ Pittsburgh, Dept Math, Pittsburgh, PA 15260 USA.
[Ben-Tal, Alona] Massey Univ, Inst Informat & Math Sci, Auckland, New Zealand.
[Smith, Jeffrey C.] NINDS, Cellular & Syst Neurobiol Sect, NIH, Bethesda, MD 20892 USA.
RP Rybak, IA (reprint author), Drexel Univ, Coll Med, Dept Neurobiol & Anat, Philadelphia, PA 19104 USA.
EM rybak@drexel.edu
RI smith, jeremy/B-7287-2012;
OI smith, jeremy/0000-0002-2978-3227; Molkov, Yaroslav/0000-0002-0862-1974
FU National Institutes of Health (NIH) [R01NS069220]; National Science
Foundation [DMS 1021701, 1312508]; Indiana University - Purdue
University, Indianapolis; NIH, National Institute of Neurological
Disorders and Stroke
FX IAR, AB-T, and NAS are funded by grant R01NS069220 from the National
Institutes of Health (NIH) (http://www.nih.gov); JER and CP are funded
by grants DMS 1021701 and 1312508 from the National Science Foundation
(http://www.nsf.gov); YIM is funded by Indiana University - Purdue
University, Indianapolis (http://http://www.iupui.edu); and JCS is
funded by Intramural Research Program of the NIH, National Institute of
Neurological Disorders and Stroke (http://www.ninds.nih.gov). The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 52
TC 9
Z9 9
U1 2
U2 15
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD OCT 10
PY 2014
VL 9
IS 10
AR e109894
DI 10.1371/journal.pone.0109894
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AR6ZS
UT WOS:000343730400091
PM 25302708
ER
PT J
AU Sheng-Fowler, L
Tu, W
Fu, HQ
Murata, H
Lanning, L
Foseh, G
Macauley, J
Blair, D
Hughes, SH
Coffin, JM
Lewis, AM
Peden, K
AF Sheng-Fowler, Li
Tu, Wei
Fu, Haiqing
Murata, Haruhiko
Lanning, Lynda
Foseh, Gideon
Macauley, Juliete
Blair, Donald
Hughes, Stephen H.
Coffin, John M.
Lewis, Andrew M., Jr.
Peden, Keith
TI A Mouse Strain Defective in Both T Cells and NK Cells Has Enhanced
Sensitivity to Tumor Induction by Plasmid DNA Expressing Both Activated
H-Ras and c-Myc
SO PLOS ONE
LA English
DT Article
ID BLADDER-CARCINOMA CELLS; TRANSFORMING GENE; IN-VIVO; TUMORIGENIC
CONVERSION; PAPILLOMAVIRUS DNA; POLYOMA-VIRUS; LINES; CANCER; MICE;
ONCOGENES
AB As part of safety studies to evaluate the risk of residual cellular DNA in vaccines manufactured in tumorigenic cells, we have been developing in vivo assays to detect and quantify the oncogenic activity of DNA. We generated a plasmid expressing both an activated human H-ras gene and murine c-myc gene and showed that 1 mu g of this plasmid, pMSV-T24-H-ras/MSV-c-myc, was capable of inducing tumors in newborn NIH Swiss mice. However, to be able to detect the oncogenicity of dominant activated oncogenes in cellular DNA, a more sensitive system was needed. In this paper, we demonstrate that the newborn CD3 epsilon transgenic mouse, which is defective in both T-cell and NK-cell functions, can detect the oncogenic activity of 25 ng of the circular form of pMSV-T24-H-ras/MSV-c-myc. When this plasmid was inoculated as linear DNA, amounts of DNA as low as 800 pg were capable of inducing tumors. Animals were found that had multiple tumors, and these tumors were independent and likely clonal. These results demonstrate that the newborn CD3 epsilon mouse is highly sensitive for the detection of oncogenic activity of DNA. To determine whether it can detect the oncogenic activity of cellular DNA derived from four human tumor-cell lines (HeLa, A549, HT-1080, and CEM), DNA (100 mu g) was inoculated into newborn CD3 epsilon mice both in the presence of 1 mu g of linear pMSV-T24-H-ras/MSV-c-myc as positive control and in its absence. While tumors were induced in 100% of mice with the positive-control plasmid, no tumors were induced in mice receiving any of the tumor DNAs alone. These results demonstrate that detection of oncogenes in cellular DNA derived from four human tumor-derived cell lines in this mouse system was not possible; the results also show the importance of including a positive-control plasmid to detect inhibitory effects of the cellular DNA.
C1 [Sheng-Fowler, Li; Tu, Wei; Fu, Haiqing; Murata, Haruhiko; Foseh, Gideon; Macauley, Juliete; Lewis, Andrew M., Jr.; Peden, Keith] US FDA, Off Vaccines Res & Review, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA.
[Lanning, Lynda] Natl Inst Allergy & Infect Dis, Rockville, MD USA.
[Blair, Donald] Natl Canc Inst, Rockville, MD USA.
[Hughes, Stephen H.; Coffin, John M.] Natl Canc Inst, Frederick Canc Res Facil, Frederick, MD USA.
[Coffin, John M.] Tufts Univ, Boston, MA 02111 USA.
RP Peden, K (reprint author), US FDA, Off Vaccines Res & Review, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA.
EM keith.peden@fda.hhs.gov
FU Division of Microbiology and Infectious Diseases of the National
Institute of Allergy and Infectious Diseases; CBER/FDA
[YI-AI-4893-02NIAID]; National Institutes of Health (NIH), National
Cancer Institute (NCI), Center for Cancer Research; NCI, NIH
[HHSN26120080001E]
FX This work was supported by a contract from the Division of Microbiology
and Infectious Diseases of the National Institute of Allergy and
Infectious Diseases through an Interagency Agreement with CBER/FDA
(contract number YI-AI-4893-02NIAID), program officer Sonnie
Kim-Grossman. SHH is supported by the Intramural Research Program of the
National Institutes of Health (NIH), National Cancer Institute (NCI),
Center for Cancer Research, and in part with funds from the NCI, NIH,
under contract HHSN26120080001E. The funders had no role in study
design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 49
TC 0
Z9 0
U1 0
U2 1
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD OCT 10
PY 2014
VL 9
IS 10
AR e108926
DI 10.1371/journal.pone.0108926
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AR6ZS
UT WOS:000343730400036
PM 25302710
ER
PT J
AU Yao, B
Hametner, S
van Gelderen, P
Merkl, H
Chen, C
Lassmann, H
Duyn, JH
Bagnato, F
AF Yao, Bing
Hametner, Simon
van Gelderen, Peter
Merkl, Hellmuth
Chen, Christina
Lassmann, Hans
Duyn, Jeff H.
Bagnato, Francesca
TI 7 Tesla Magnetic Resonance Imaging to Detect Cortical Pathology in
Multiple Sclerosis
SO PLOS ONE
LA English
DT Article
ID GRADIENT-ECHO MRI; WHITE-MATTER; HUMAN BRAIN; BIOPHYSICAL MECHANISMS;
LESION DETECTION; CEREBRAL-CORTEX; CONTRAST; IRON; HETEROGENEITY; PHASE
AB Background: Neocortical lesions (NLs) are an important pathological component of multiple sclerosis (MS), but their visualization by magnetic resonance imaging (MRI) remains challenging.
Objectives: We aimed at assessing the sensitivity of multi echo gradient echo (ME-GRE) T-2*-weighted MRI at 7.0 Tesla in depicting NLs compared to myelin and iron staining.
Methods: Samples from two MS patients were imaged post mortem using a whole body 7T MRI scanner with a 24-channel receive-only array. Isotropic 200 micron resolution images with varying T-2* weighting were reconstructed from the ME-GRE data and converted into R-2* maps. Immunohistochemical staining for myelin (proteolipid protein, PLP) and diaminobenzidine-enhanced Turnbull blue staining for iron were performed.
Results: Prospective and retrospective sensitivities of MRI for the detection of NLs were 48% and 67% respectively. We observed MRI maps detecting only a small portion of 20 subpial NLs extending over large cortical areas on PLP stainings. No MRI signal changes suggestive of iron accumulation in NLs were observed. Conversely, R-2* maps indicated iron loss in NLs, which was confirmed by histological quantification.
Conclusions: High-resolution post mortem imaging using R-2* and magnitude maps permits detection of focal NLs. However, disclosing extensive subpial demyelination with MRI remains challenging.
C1 [Yao, Bing; van Gelderen, Peter; Merkl, Hellmuth; Duyn, Jeff H.] NINDS, Adv Magnet Resonance Imaging Sect, Lab Funct & Mol Imaging, NIH, Bethesda, MD 20892 USA.
[Yao, Bing] Kessler Fdn, Ctr Neuroimaging Res, W Orange, NJ USA.
[Hametner, Simon; Lassmann, Hans] Med Univ, Ctr Brain Res, Vienna, Austria.
[Chen, Christina; Bagnato, Francesca] NINDS, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA.
[Bagnato, Francesca] Vanderbilt Univ, Inst Imaging Sci, Dept Radiol & Radiol Sci, Nashville, TN 37235 USA.
RP Bagnato, F (reprint author), NINDS, Neuroimmunol Branch, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
EM fbagnato@umm.edu
FU Intramural Research Program of the NINDS, NIH; Austrian Science Fund
[P19854-B02]
FX This research was supported by the Intramural Research Program of the
NINDS, NIH and by the Austrian Science Fund (Project P19854-B02). The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 40
TC 19
Z9 19
U1 0
U2 6
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD OCT 10
PY 2014
VL 9
IS 10
AR e108863
DI 10.1371/journal.pone.0108863
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AR6ZS
UT WOS:000343730400031
PM 25303286
ER
PT J
AU Shimura, E
Shibui, A
Narushima, S
Nambu, A
Yamaguchi, S
Akitsu, A
Leonard, WJ
Iwakura, Y
Matsumoto, K
Suto, H
Okumura, K
Sudo, K
Nakae, S
AF Shimura, Eri
Shibui, Akiko
Narushima, Seiko
Nambu, Aya
Yamaguchi, Sachiko
Akitsu, Aoi
Leonard, Warren J.
Iwakura, Yoichiro
Matsumoto, Kenji
Suto, Hajime
Okumura, Ko
Sudo, Katsuko
Nakae, Susumu
TI Potential role of myeloid cell/eosinophil-derived IL-17 in LPS-induced
endotoxin shock
SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
LA English
DT Article
DE IL-17A; IL-17F; IL-25; Sepsis
ID REGULATORY T-CELLS; POLYMICROBIAL SEPSIS; INFLAMMATORY RESPONSES;
IMMUNE-RESPONSE; FAMILY-MEMBERS; HOST-DEFENSE; B-CELLS; MICE;
IDENTIFICATION; INFECTION
AB IL-17RA is a shared receptor subunit for several cytokines of the IL-17 family, including IL-17A, IL-17C, IL-17E (also called IL-25) and IL-17F. It has been shown that mice deficient in IL-17RA are more susceptible to sepsis than wild-type mice, suggesting that IL-17RA is important for host defense against sepsis. However, it is unclear which ligands for IL-17RA, such as IL-17A, IL-17C, IL-17E/IL-25 and/or IL-17F, are involved in the pathogenesis of sepsis. Therefore, we examined IL-17A, IL-17E/IL-25 and IL-17F for possible involvement in LPS-induced endotoxin shock. IL-17A-deficient mice, but not IL-25- or IL-17F-deficient mice, were resistant to LPS-induced endotoxin shock, as compared with wild-type mice. Nevertheless, studies using 1-6-deficient, IL-21 Rot-deficient and Rag-2-deficient mice, revealed that neither IL-6 and IL-21, both of which are important for Th17 cell differentiation, nor Th17 cells were essential for the development of LPS-induced endotoxin shock, suggesting that IL-17A-producing cells other than Th17 cells were important in the setting. In this connection, IL-17A was produced by macrophages, DCs and eosinophils after LPS injection. Taken together, these findings indicate that IL-17A, but not IL-17F or IL-25, is crucial for LPS-induced endotoxin shock. In addition, macrophages, DCs and eosinophils, but not Th17 cells or gamma delta T cells, may be sources of IL-17A during LPS-induced endotoxin shock. (C) 2014 Elsevier Inc. All rights reserved.
C1 [Shimura, Eri; Suto, Hajime; Okumura, Ko] Juntendo Univ, Atopy Res Ctr, Tokyo 1138412, Japan.
[Shibui, Akiko] Univ Tokyo, Grad Sch Frontier Sci, Dept Med Genom, Chiba 2778561, Japan.
[Narushima, Seiko; Nambu, Aya; Yamaguchi, Sachiko; Nakae, Susumu] Univ Tokyo, Inst Med Sci, Ctr Expt Med & Syst Biol, Lab Syst Biol, Tokyo 1088639, Japan.
[Akitsu, Aoi; Iwakura, Yoichiro] Tokyo Univ Sci, Div Expt Anim Immunol, Chiba 2788510, Japan.
[Leonard, Warren J.] NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA.
[Leonard, Warren J.] NHLBI, Ctr Immunol, NIH, Bethesda, MD 20892 USA.
[Matsumoto, Kenji] Natl Res Inst Child Hlth & Dev, Dept Allergy & Immunol, Tokyo 1578535, Japan.
[Sudo, Katsuko] Tokyo Med Univ, Anim Res Ctr, Tokyo 1608402, Japan.
[Nakae, Susumu] Japan Sci & Technol Agcy, Precursory Res Embryon Sci & Technol PRESTO, Kawaguchi, Saitama 3320012, Japan.
RP Nakae, S (reprint author), Univ Tokyo, Inst Med Sci, Ctr Expt Med & Syst Biol, Lab Syst Biol,Minato Ku, 4-6-1 Shirokanedai, Tokyo 1088639, Japan.
EM snakae@ims.u-tokyo.ac.jp
RI Iwakura, Yoichiro/E-5457-2011
OI Iwakura, Yoichiro/0000-0002-9934-5775
FU Ministry of Education, Culture, Sports, Science and Technology (MEXT);
Ministry of Health, Labour and Welfare, Japan; National Center for Child
Health and Development [23A-5]; Precursory Research for Embryonic
Science and Technology, Japan Science and Technology Agency; Division of
Intra-mural Research, National Heart, Lung, and Blood Institute, NIH,
Bethesda, MD
FX We thank Wakako Nakanishi, Yoshihisa Hiraishi, Ayano Yamauchi-Ishii,
Tsubasa Sato and Hiromi Iwami for their technical assistance. We also
thank Lawrence W. Stiver (Tokyo, Japan) for his critical reading of the
manuscript. This work was supported by Grants-in-Aid for Young
Scientists (B) (E.S.), Grants-in-Aid for Young Scientists (A) (S. Nakae)
from the Ministry of Education, Culture, Sports, Science and Technology
(MEXT), Health Labour Sciences Research Grants from the Ministry of
Health, Labour and Welfare, Japan (K.M.), The Grant of National Center
for Child Health and Development (23A-5) (K.M.), and Precursory Research
for Embryonic Science and Technology, Japan Science and Technology
Agency (S. Nakae.). W.J.L. was supported by the Division of Intra-mural
Research, National Heart, Lung, and Blood Institute, NIH, Bethesda, MD.
NR 34
TC 3
Z9 3
U1 0
U2 12
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0006-291X
EI 1090-2104
J9 BIOCHEM BIOPH RES CO
JI Biochem. Biophys. Res. Commun.
PD OCT 10
PY 2014
VL 453
IS 1
BP 1
EP 6
DI 10.1016/j.bbrc.2014.09.004
PG 6
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA AR5OZ
UT WOS:000343634900001
PM 25204502
ER
PT J
AU Ustun, C
Reiter, A
Scott, BL
Nakamura, R
Damaj, G
Kreil, S
Shanley, R
Hogan, WJ
Perales, MA
Shore, T
Baurmann, H
Stuart, R
Gruhn, B
Doubek, M
Hsu, JW
Tholouli, E
Gromke, T
Godley, LA
Pagano, L
Gilman, A
Wagner, EM
Shwayder, T
Bornhauser, M
Papadopoulos, EB
Bohm, A
Vercellotti, G
Van Lint, MT
Schmid, C
Rabitsch, W
Pullarkat, V
Legrand, F
Yakoub-agha, I
Saber, W
Barrett, J
Hermine, O
Hagglund, H
Sperr, WR
Popat, U
Alyea, EP
Devine, S
Deeg, HJ
Weisdorf, D
Akin, C
Valent, P
AF Ustun, Celalettin
Reiter, Andreas
Scott, Bart L.
Nakamura, Ryotaro
Damaj, Gandhi
Kreil, Sebastian
Shanley, Ryan
Hogan, William J.
Perales, Miguel-Angel
Shore, Tsiporah
Baurmann, Herrad
Stuart, Robert
Gruhn, Bernd
Doubek, Michael
Hsu, Jack W.
Tholouli, Eleni
Gromke, Tanja
Godley, Lucy A.
Pagano, Livio
Gilman, Andrew
Wagner, Eva Maria
Shwayder, Tor
Bornhaeuser, Martin
Papadopoulos, Esperanza B.
Boehm, Alexandra
Vercellotti, Gregory
Van Lint, Maria Teresa
Schmid, Christoph
Rabitsch, Werner
Pullarkat, Vinod
Legrand, Faezeh
Yakoub-agha, Ibrahim
Saber, Wael
Barrett, John
Hermine, Olivier
Hagglund, Hans
Sperr, Wolfgang R.
Popat, Uday
Alyea, Edwin P.
Devine, Steven
Deeg, H. Joachim
Weisdorf, Daniel
Akin, Cem
Valent, Peter
TI Hematopoietic Stem-Cell Transplantation for Advanced Systemic
Mastocytosis
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID ACUTE MYELOID-LEUKEMIA; BONE-MARROW-TRANSPLANTATION; NEOPLASTIC
MAST-CELLS; C-KIT MUTATIONS; TYROSINE KINASE INHIBITORS;
CHROMOSOME-NEGATIVE ACUTE; MINIMAL RESIDUAL DISEASE; 1ST COMPLETE
REMISSION; LINEAGE DISEASE; PROGNOSTIC IMPACT
AB Purpose
Advanced systemic mastocytosis (SM), a fatal hematopoietic malignancy characterized by drug resistance, has no standard therapy. The effectiveness of allogeneic hematopoietic stem-cell transplantation (alloHCT) in SM remains unknown.
Patients and Methods
In a global effort to define the value of HCT in SM, 57 patients with the following subtypes of SM were evaluated: SM associated with clonal hematologic non-mast cell disorders (SM-AHNMD; n = 38), mast cell leukemia (MCL; n = 12), and aggressive SM (ASM; n = 7). Median age of patients was 46 years (range, 11 to 67 years). Donors were HLA-identical (n = 34), unrelated (n = 17), umbilical cord blood (n = 2), HLA-haploidentical (n = 1), or unknown (n = 3). Thirty-six patients received myeloablative conditioning (MAC), and 21 patients received reduced-intensity conditioning (RIC).
Results
Responses in SM were observed in 40 patients (70%), with complete remission in 16 patients (28%). Twelve patients (21%) had stable disease, and five patients (9%) had primary refractory disease. Overall survival (OS) at 3 years was 57% for all patients, 74% for patients with SM-AHNMD, 43% for those with ASM, and 17% for those with MCL. The strongest risk factor for poor OS was MCL. Survival was also lower in patients receiving RIC compared with MAC and in patients having progression compared with patients having stable disease or response.
Conclusion AlloHCT was associated with long-term survival in patients with advanced SM. Although alloHCT may be considered as a viable and potentially curative therapeutic option for advanced SM in the meantime, given that this is a retrospective analysis with no control group, the definitive role of alloHCT will need to be determined by a prospective trial. (C) 2014 by American Society of Clinical Oncology
C1 [Ustun, Celalettin; Shanley, Ryan; Vercellotti, Gregory; Weisdorf, Daniel] Univ Minnesota, Minneapolis, MN 55455 USA.
[Hogan, William J.] Mayo Clin, Rochester, MN USA.
[Reiter, Andreas; Kreil, Sebastian] Univ Med Mannheim, Mannheim, Germany.
[Baurmann, Herrad] Stiftung Deutsch Klin Diagnost, Wiesbaden, Germany.
[Gruhn, Bernd] Jena Univ Hosp, Jena, Germany.
[Gromke, Tanja] Univ Essen Gesamthsch, Essen, Germany.
[Wagner, Eva Maria] Univ Med Mainz, Mainz, Germany.
[Bornhaeuser, Martin] Univ Klinikum Dresden, Dresden, Germany.
[Schmid, Christoph] Klinikum Augsburg, Augsburg, Germany.
[Scott, Bart L.; Deeg, H. Joachim] Univ Washington, Seattle, WA 98195 USA.
[Nakamura, Ryotaro] City Hope Natl Med Ctr, Duarte, CA 91010 USA.
[Pullarkat, Vinod] Univ So Calif, Los Angeles, CA USA.
[Damaj, Gandhi] Univ Caen, Fac Med, F-14032 Caen, France.
[Legrand, Faezeh] Nice Univ Hosp, Nice, France.
[Legrand, Faezeh] SFGM TC, Lille, France.
[Yakoub-agha, Ibrahim] CHU Lille, F-59037 Lille, France.
[Hermine, Olivier] Univ Paris 05, Hop Necker Enfants Malad, AP HP, Fac Med, Paris, France.
[Hermine, Olivier] AP HP Necker Enfants Malades, Paris, France.
[Hermine, Olivier] Ctr Reference Mastocytoses, Paris, France.
[Perales, Miguel-Angel; Papadopoulos, Esperanza B.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
[Shore, Tsiporah] New York Presbyterian Hosp, Weill Cornell Med Ctr, New York, NY 10021 USA.
[Stuart, Robert] Med Univ S Carolina, Charleston, SC 29425 USA.
[Doubek, Michael] Masaryk Univ, Brno, Czech Republic.
[Hsu, Jack W.] Univ Florida, Gainesville, FL USA.
[Tholouli, Eleni] Manchester Royal Infirm, Manchester M13 9WL, Lancs, England.
[Godley, Lucy A.] Univ Chicago, Chicago, IL 60637 USA.
[Pagano, Livio] Univ Cattolica Sacro Cuore, I-20123 Milan, Italy.
[Van Lint, Maria Teresa] Ist Ricovero & Cura Carattere Sci San Martino IST, Genoa, Italy.
[Gilman, Andrew] Levine Childrens Hosp, Charlotte, NC USA.
[Shwayder, Tor] Henry Ford Hosp, Detroit, MI 48202 USA.
[Boehm, Alexandra] Elisabethinen Hosp, Linz, Austria.
[Rabitsch, Werner; Sperr, Wolfgang R.; Valent, Peter] Med Univ Vienna, Vienna, Austria.
[Saber, Wael] Med Coll Wisconsin, Milwaukee, WI 53226 USA.
[Barrett, John] NHLBI, Bethesda, MD 20892 USA.
[Hagglund, Hans] Karolinska Univ Hosp, Stockholm, Sweden.
[Popat, Uday] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Alyea, Edwin P.; Akin, Cem] Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA.
[Devine, Steven] Ohio State Univ, Columbus, OH 43210 USA.
RP Ustun, C (reprint author), Univ Minnesota, Dept Med, 14-142 PWB,516 Delaware St SE, Minneapolis, MN 55455 USA.
EM custun@umn.edu
OI Akin, Cem/0000-0001-6301-4520
FU NCATS NIH HHS [UL1 TR000114, UL1 TR000430]; NCI NIH HHS [P30 CA077598,
U24 CA076518]
NR 77
TC 25
Z9 25
U1 0
U2 13
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 OCT 10
PY 2014
VL 32
IS 29
BP 3264
EP +
DI 10.1200/JCO.2014.55.2018
PG 18
WC Oncology
SC Oncology
GA AQ7JC
UT WOS:000342988000011
PM 25154823
ER
PT J
AU Sherman, ME
Piedmonte, M
Mai, PL
Ioffe, OB
Ronnett, BM
Van Le, L
Ivanov, I
Bell, MC
Blank, SV
DiSilvestro, P
Hamilton, CA
Tewari, KS
Wakeley, K
Kauff, ND
Yamada, SD
Rodriguez, G
Skates, SJ
Alberts, DS
Walker, JL
Minasian, L
Lu, K
Greene, MH
AF Sherman, Mark E.
Piedmonte, Marion
Mai, Phuong L.
Ioffe, Olga B.
Ronnett, Brigitte M.
Van Le, Linda
Ivanov, Iouri
Bell, Maria C.
Blank, Stephanie V.
DiSilvestro, Paul
Hamilton, Chad A.
Tewari, Krishnansu S.
Wakeley, Katie
Kauff, Noah D.
Yamada, S. Diane
Rodriguez, Gustavo
Skates, Steven J.
Alberts, David S.
Walker, Joan L.
Minasian, Lori
Lu, Karen
Greene, Mark H.
TI Pathologic Findings at Risk-Reducing Salpingo-Oophorectomy: Primary
Results From Gynecologic Oncology Group Trial GOG-0199
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID BRCA MUTATION CARRIERS; EPITHELIAL OVARIAN-CANCER; UTERINE SEROUS
CARCINOMA; HEREDITARY HIGH-RISK; GERM-LINE MUTATION; FALLOPIAN-TUBE;
PROPHYLACTIC OOPHORECTOMY; ORAL-CONTRACEPTIVES; WOMEN; BREAST
AB Purpose
Risk-reducing salpingo-oophorectomy (RRSO) lowers mortality from ovarian/tubal and breast cancers among BRCA1/2 mutation carriers. Uncertainties persist regarding potential benefits of RRSO among high-risk noncarriers, optimal surgical age, and anatomic origin of clinically occult cancers detected at surgery. To address these topics, we analyzed surgical treatment arm results from Gynecologic Oncology Group Protocol-0199 (GOG-0199), the National Ovarian Cancer Prevention and Early Detection Study.
Participants and Methods
This analysis included asymptomatic high-risk women age >= 30 years who elected RRSO at enrollment. Women provided risk factor data and underwent preoperative cancer antigen 125 (CA-125) serum testing and transvaginal ultrasound (TVU). RRSO specimens were processed according to a standardized tissue processing protocol and underwent central pathology panel review. Research-based BRCA1/2 mutation testing was performed when a participant's mutation status was unknown at enrollment. Relationships between participant characteristics and diagnostic findings were assessed using univariable statistics and multivariable logistic regression.
Results
Invasive or intraepithelial ovarian/tubal/peritoneal neoplasms were detected in 25 (2.6%) of 966 RRSOs (BRCA1 mutation carriers, 4.6%; BRCA2 carriers, 3.5%; and noncarriers, 0.5%; P < .001). In multivariable models, positive BRCA1/2 mutation status (P = .0056), postmenopausal status (P = .0023), and abnormal CA-125 levels and/or TVU examinations (P < .001) were associated with detection of clinically occult neoplasms at RRSO. For 387 women with negative BRCA1/2 mutation testing and normal CA-125 levels, findings at RRSO were benign.
Conclusion
Clinically occult cancer was detected among 2.6% of high-risk women undergoing RRSO. BRCA1/2 mutation, postmenopausal status, and abnormal preoperative CA-125 and/or TVU were associated with cancer detection at RRSO. These data can inform management decisions among women at high risk of ovarian/tubal cancer. (C) 2014 by American Society of Clinical Oncology
C1 [Sherman, Mark E.; Mai, Phuong L.; Minasian, Lori; Greene, Mark H.] NCI, Rockville, MD 20850 USA.
[Ioffe, Olga B.] Univ Maryland, Med Ctr, Baltimore, MD 21201 USA.
[Ronnett, Brigitte M.] Johns Hopkins Med Inst, Baltimore, MD 21205 USA.
[Hamilton, Chad A.] Walter Reed Natl Mil Med Ctr, Bethesda, MD USA.
[Piedmonte, Marion] Roswell Pk Canc Inst, Buffalo, NY 14263 USA.
[Blank, Stephanie V.] NYU, Sch Med, New York, NY USA.
[Kauff, Noah D.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
[Van Le, Linda] Univ N Carolina, Chapel Hill, NC USA.
[Ivanov, Iouri] Columbus Canc Council, Columbus, OH USA.
[Bell, Maria C.] Sanford Univ, South Dakota Med Ctr, Sioux Falls, SD USA.
[DiSilvestro, Paul] Brown Univ, Women & Infants Hosp, Providence, RI USA.
[Tewari, Krishnansu S.] Univ Calif Med Ctr Irvine, Orange, CA USA.
[Wakeley, Katie] Tufts Univ, Boston, MA 02111 USA.
[Skates, Steven J.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Yamada, S. Diane] Univ Chicago, Chicago, IL 60637 USA.
[Rodriguez, Gustavo] North Shore Univ Hlth Syst, Evanston, IL USA.
[Alberts, David S.] Univ Arizona, Ctr Canc, Tucson, AZ USA.
[Walker, Joan L.] Univ Oklahoma, Oklahoma City, OK USA.
[Lu, Karen] Univ Texas Houston, MD Anderson Canc Ctr, Houston, TX 77030 USA.
RP Greene, MH (reprint author), NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, NIH, 9609 Med Ctr Dr,Room 6E-454, Rockville, MD 20850 USA.
EM greenem@mail.nih.gov
OI Kauff, Noah/0000-0001-7242-6156
FU Intramural NIH HHS; NCATS NIH HHS [UL1 TR000430]; NCI NIH HHS [UG1
CA189867, U10 CA037517, U10 CA101165, P30 CA016672, U01 CA152990, U10
CA180822, CA 37517, U10 CA180838, U10 CA027469, CA 27469, CA101165]
NR 71
TC 21
Z9 21
U1 1
U2 7
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 OCT 10
PY 2014
VL 32
IS 29
BP 3275
EP +
DI 10.1200/JCO.2013.54.1987
PG 10
WC Oncology
SC Oncology
GA AQ7JC
UT WOS:000342988000012
PM 25199754
ER
PT J
AU Wong, JR
Morton, LM
Tucker, MA
Abramson, DH
Seddon, JM
Sampson, JN
Kleinerman, RA
AF Wong, Jeannette R.
Morton, Lindsay M.
Tucker, Margaret A.
Abramson, David H.
Seddon, Johanna M.
Sampson, Joshua N.
Kleinerman, Ruth A.
TI Risk of Subsequent Malignant Neoplasms in Long-Term Hereditary
Retinoblastoma Survivors After Chemotherapy and Radiotherapy
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID CHILDHOOD-CANCER SURVIVOR; RADIATION-RELATED RISK; SOFT-TISSUE SARCOMAS;
2ND PRIMARY TUMORS; INTRAOCULAR RETINOBLASTOMA; BONE SARCOMAS;
FOLLOW-UP; BRITAIN; MUTATIONS; MORTALITY
AB Purpose
Hereditary retinoblastoma (Rb) survivors have increased risk of subsequent malignant neoplasms (SMNs). Previous studies reported elevated radiotherapy (RT) -related SMN risks, but less is known about chemotherapy-related risks.
Patients and Methods
In a long-term follow-up study of 906 5-year hereditary Rb survivors diagnosed from 1914 to 1996 and observed through 2009, treatment-related SMN risks were quantified using cumulative incidence analyses and multivariable Cox proportional hazards regression models with age as the underlying time scale.
Results Nearly 90% of Rb survivors were treated with RT, and almost 40% received alkylating agent (AA) containing chemotherapy (predominantly triethylenemelamine). Median follow-up time to first SMN diagnosis was 26.3 years. Overall SMN risk was not significantly elevated among survivors receiving AA plus RT versus RT without chemotherapy (hazard ratio [HR], 1.27; 95% Cl, 0.99 to 1.63). AA-related risks were significantly increased for subsequent bone tumors (HR, 1.60; 95% Cl, 1.03 to 2.49) and leiomyosarcoma (HR, 2.67; 95% Cl, 1.22 to 5.85) but not for melanoma (HR, 0.74; 95% Cl, 0.36 to 1.55) or epithelial tumors (HR, 0.89; 95% Cl, 0.48 to 1.64). Leiomyosarcoma risk was significantly increased for survivors who received AAs at age < 1 (HR, 5.17; 95% Cl, 1.76 to 15.17) but not for those receiving AAs at age >= 1 year (HR, 1.75; 95% Cl, 0.68 to 4.51). Development of leiomyosarcoma was significantly more common after AA plus RT versus RT (5.8% v 1.6% at age 40 years; P = .01).
Conclusion This comprehensive quantification of SMN risk after chemotherapy and RT among hereditary Rb survivors also demonstrates an AA-related contribution to risk. Although triethylenemelamine is no longer prescribed, our findings warrant further follow-up to investigate potential SMN risks associated with current chemotherapies used for Rb. (C) 2014 by American Society of Clinical Oncology
C1 [Wong, Jeannette R.; Morton, Lindsay M.; Tucker, Margaret A.; Sampson, Joshua N.; Kleinerman, Ruth A.] NCI, Bethesda, MD 20892 USA.
[Abramson, David H.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
[Seddon, Johanna M.] Tufts Univ New England Med Ctr, Boston, MA USA.
RP Kleinerman, RA (reprint author), 9609 Med Ctr Dr,Room 7E536, Bethesda, MD 20892 USA.
EM kleinerr@exchange.nih.gov
RI Tucker, Margaret/B-4297-2015; Morton, Lindsay/B-5234-2015;
OI Morton, Lindsay/0000-0001-9767-2310; Kleinerman,
Ruth/0000-0001-7415-2478
FU National Institutes of Health; National Cancer Institute
FX Supported by the Intramural Research Program of the National Institutes
of Health and the National Cancer Institute.
NR 60
TC 18
Z9 18
U1 0
U2 6
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 OCT 10
PY 2014
VL 32
IS 29
BP 3284
EP +
DI 10.1200/JCO.2013.54.7844
PG 9
WC Oncology
SC Oncology
GA AQ7JC
UT WOS:000342988000013
PM 25185089
ER
PT J
AU Mazaheri, A
Nishikawa, H
AF Mazaheri, Alireza
Nishikawa, Hiroaki
TI Very efficient high-order hyperbolic schemes for time-dependent
advection-diffusion problems: Third-, fourth-, and sixth-order
SO COMPUTERS & FLUIDS
LA English
DT Article
DE Higher-order; Residual distribution; Unsteady; Nonlinear; Navier-Stokes
ID RESIDUAL DISTRIBUTION SCHEMES; STEADY; MESHES
AB In this paper, we construct very efficient high-order schemes for general time-dependent advection-diffusion problems, based on the first-order hyperbolic system method. Extending the previous work on the second-order time-dependent hyperbolic advection-diffusion scheme (Mazaheri and Nishikawa, NASA/TM-2014-218175, 2014), we construct third-, fourth-, and sixth-order accurate schemes by modifying the source term discretization. In this paper, two techniques for the source term discretization are proposed; (I) reformulation of the source terms with their divergence forms and (2) correction to the trapezoidal rule for the source term discretization. We construct spatially third- and fourth-order schemes from the former technique. These schemes require computations of the gradients and second-derivatives of the source terms. From the latter technique, we construct spatially third-, fourth-, and sixth-order schemes by using the gradients and second-derivatives for the source terms, except the fourth-order scheme, which does not require the second derivatives of the source term and thus is even less computationally expensive than the third-order schemes. We then construct high-order time-accurate schemes by incorporating a high-order backward difference formula as a source term. These schemes are very efficient in that high-order accuracy is achieved for both the solution and the gradient only by the improved source term discretization. A very rapid Newton-type convergence is achieved by a compact second-order Jacobian formulation. The numerical results are presented for both steady and time-dependent linear and nonlinear advection-diffusion problems, demonstrating these powerful features. Published by Elsevier Ltd.
C1 [Mazaheri, Alireza] NASA, Langley Res Ctr, Hampton, VA 23681 USA.
[Nishikawa, Hiroaki] NIA, Hampton, VA 23666 USA.
RP Mazaheri, A (reprint author), NASA, Langley Res Ctr, Hampton, VA 23681 USA.
EM ali.r.mazaheri@nasa.gov
RI Nishikawa, Hiroaki/M-1247-2016
OI Nishikawa, Hiroaki/0000-0003-4472-5313
FU U.S. Army Research Office [W911NF-12-1-0154]
FX The second author is supported by the U.S. Army Research Office under
the Contract/Grant Number W911NF-12-1-0154.
NR 24
TC 7
Z9 7
U1 0
U2 4
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0045-7930
EI 1879-0747
J9 COMPUT FLUIDS
JI Comput. Fluids
PD OCT 10
PY 2014
VL 102
BP 131
EP 147
DI 10.1016/j.compfluid.2014.06.020
PG 17
WC Computer Science, Interdisciplinary Applications; Mechanics
SC Computer Science; Mechanics
GA AP7RL
UT WOS:000342274300013
ER
PT J
AU Yan, Y
Newman, AH
Xu, M
AF Yan, Y.
Newman, A. H.
Xu, M.
TI DOPAMINE D1 AND D3 RECEPTORS MEDIATE RECONSOLIDATION OF COCAINE MEMORIES
IN MOUSE MODELS OF DRUG SELF-ADMINISTRATION
SO NEUROSCIENCE
LA English
DT Article
DE dopamine D1 and D3 receptors; reconsolidation; drug memory; antagonists;
gene mutation; cocaine self-administration
ID NUCLEUS-ACCUMBENS CORE; METHAMPHETAMINE-SEEKING BEHAVIOR; CUE-INDUCED
REINSTATEMENT; BASOLATERAL AMYGDALA; MUTANT MICE; PROTEIN-SYNTHESIS;
GENE-EXPRESSION; KNOCKOUT MICE; ANIMAL-MODELS; D-3 RECEPTORS
AB Memories of drug experience and drug-associated environmental cues can elicit drug-seeking and taking behaviors in humans. Disruption of reconsolidation of drug memories dampens previous memories and therefore may provide a useful way to treat drug abuse. We and others previously demonstrated that dopamine D1 and D3 receptors play differential roles in acquiring cocaine-induced behaviors. Moreover, D3 receptors contribute to the reconsolidation of cocaine-induced conditioned place preference. In the present study, we examined effects of manipulating D1 or D3 receptors on reconsolidation of cocaine memories in mouse models of drug self-administration. We found that pharmacological blockade of D1 receptors or a genetic mutation of the D3 receptor gene attenuated reconsolidation that lasted for at least 1 week after the memory retrieval. In contrast, with no memory retrieval, pharmacological antagonism of D1 receptors or the D3 receptor gene mutation did not significantly affect reconsolidation of cocaine memories. Pharmacological blockade of D3 receptors also attenuated reconsolidation in wild-type mice that lasted for at least 1 week after the memory retrieval. These results suggest that D1 and D3 receptors and related signaling mechanisms play key roles in reconsolidation of cocaine memories in mice, and that these receptors may serve as novel targets for the treatment of cocaine abuse in humans. (C) 2014 IBRO. Published by Elsevier Ltd. All rights reserved.
C1 [Yan, Y.; Xu, M.] Univ Chicago, Dept Anesthesia & Crit Care, Chicago, IL 60637 USA.
[Newman, A. H.] NIDA, Med Chem Sect, Intramural Res Program, NIH, Baltimore, MD USA.
RP Xu, M (reprint author), Univ Chicago, Dept Anesthesia & Crit Care, Box 428, Chicago, IL 60637 USA.
EM mxu@dacc.uchicago.edu
FU NIDA [DA025088]; CTSA [UL1 TR000430]; NIDA Intramural Research Program
FX We greatly appreciate Qin Zheng for genotyping mice, and J. Cao for
synthesizing PG01037. M.X. was supported by a grant from NIDA
(DA025088), and from CTSA UL1 TR000430. A.H.N was supported by the NIDA
Intramural Research Program.
NR 88
TC 5
Z9 5
U1 1
U2 8
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 OCT 10
PY 2014
VL 278
BP 154
EP 164
DI 10.1016/j.neuroscience.2014.08.008
PG 11
WC Neurosciences
SC Neurosciences & Neurology
GA AP4OZ
UT WOS:000342058700016
PM 25149631
ER
PT J
AU Fernandez, P
Scaffidi, P
Markert, E
Lee, JH
Rane, S
Misteli, T
AF Fernandez, Patricia
Scaffidi, Paola
Markert, Elke
Lee, Ji-Hyeon
Rane, Sushil
Misteli, Tom
TI Transformation Resistance in a Premature Aging Disorder Identifies a
Tumor-Protective Function of BRD4
SO CELL REPORTS
LA English
DT Article
ID HUTCHINSON-GILFORD-PROGERIA; BET BROMODOMAIN INHIBITION; ACUTE
MYELOID-LEUKEMIA; BREAST-CANCER; DNA-DAMAGE; C-MYC; LAMIN; CHROMATIN;
CELLS; SURVIVAL
AB Advanced age and DNA damage accumulation are prominent risk factors for cancer. The premature aging disorder Hutchinson-Gilford progeria syndrome (HGPS) provides a unique opportunity for studying the interplay between DNA damage and aging-associated tumor mechanisms, given that HGPS patients do not develop tumors despite elevated levels of DNA damage. Here, we have used HGPS patient cells to identify a protective mechanism to oncogenesis. We find that HGPS cells are resistant to neoplastic transformation. Resistance is mediated by the bromodomain protein BRD4, which exhibits altered genome-wide binding patterns in transformation-resistant cells, leading to inhibition of oncogenic dedifferentiation. BRD4 also inhibits, albeit to a lower extent, the tumorigenic potential of transformed cells from healthy individuals. BRD4-mediated tumor protection is clinically relevant given that a BRD4 gene signature predicts positive clinical outcome in breast and lung cancer. Our results demonstrate a protective function for BRD4 and suggest tissue-specific roles for BRD4 in tumorigenesis.
C1 [Fernandez, Patricia; Scaffidi, Paola; Misteli, Tom] NCI, NIH, Bethesda, MD 20892 USA.
[Scaffidi, Paola] Canc Res UK London Res Inst, Lincolns Inn Fields Labs, Canc Epigenet Lab, London WC2A 3PX, England.
[Scaffidi, Paola] UCL, UCL Canc Inst, London WC1E 6DD, England.
[Markert, Elke] Rutgers Canc Inst New Jersey, New Brunswick, NJ 08903 USA.
[Markert, Elke] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Med, New Brunswick, NJ 08901 USA.
[Lee, Ji-Hyeon; Rane, Sushil] NIDDK, NIH, Bethesda, MD 20892 USA.
RP Misteli, T (reprint author), NCI, NIH, Bethesda, MD 20892 USA.
EM mistelit@mail.nih.gov
FU Instituto de Salud Carlos III; Intramural Research Program of the NIH,
National Cancer Institute, Center for Cancer Research; Ellison Medical
Research Foundation
FX We thank Peter Adams, Keiko Ozato, and Kent Hunter for helpful
discussions; James Bradner, Peter Howley, William Hahn, Robert Weinberg,
Peter Adams, Thijn Brummelkamp, Anup Dey, and William Lockwood for
providing reagents; Vassilis Roukos and Nard Kubben for support with
imaging; Anand Merchant for help with microarray analysis; and Han Si
and Margaret Cam for help with ChIP-seq analysis. Fluorescence imaging
was performed at the NCI Fluorescence Imaging Facility and the NCI
High-Throughput Imaging Facility. P.F. was supported by the Instituto de
Salud Carlos III. This project was funded the Intramural Research
Program of the NIH, National Cancer Institute, Center for Cancer
Research, and a grant from the Ellison Medical Research Foundation.
NR 53
TC 12
Z9 12
U1 1
U2 8
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 OCT 9
PY 2014
VL 9
IS 1
BP 248
EP 260
DI 10.1016/j.celrep.2014.08.069
PG 13
WC Cell Biology
SC Cell Biology
GA AS7YP
UT WOS:000344468100022
PM 25284786
ER
PT J
AU Hyatt, LD
Wasserman, GA
Rah, YJ
Matsuura, KY
Coleman, FT
Hilliard, KL
Pepper-Cunningham, ZA
Ieong, M
Stumpo, DJ
Blackshear, PJ
Quinton, LJ
Mizgerd, JP
Jones, MR
AF Hyatt, Lynnae D.
Wasserman, Gregory A.
Rah, Yoon J.
Matsuura, Kori Y.
Coleman, Fadie T.
Hilliard, Kristie L.
Pepper-Cunningham, Zachary Ash
Ieong, Michael
Stumpo, Deborah J.
Blackshear, Perry J.
Quinton, Lee J.
Mizgerd, Joseph P.
Jones, Matthew R.
TI Myeloid ZFP36L1 Does Not Regulate Inflammation or Host Defense in Mouse
Models of Acute Bacterial Infection
SO PLOS ONE
LA English
DT Article
ID TUMOR-NECROSIS-FACTOR; AU-RICH ELEMENT; MESSENGER-RNA TURNOVER;
ZINC-FINGER PROTEINS; TRISTETRAPROLIN-DEFICIENCY SYNDROME;
VENTILATOR-ASSOCIATED PNEUMONIA; ACUTE-PHASE RESPONSE; KAPPA-B RELA;
PNEUMOCOCCAL PNEUMONIA; NEUTROPHIL RECRUITMENT
AB Zinc finger protein 36, C3H type-like 1 (ZFP36L1) is one of several Zinc Finger Protein 36 (Zfp36) family members, which bind AU rich elements within 39 untranslated regions (UTRs) to negatively regulate the post-transcriptional expression of targeted mRNAs. The prototypical member of the family, Tristetraprolin (TTP or ZFP36), has been well-studied in the context of inflammation and plays an important role in repressing pro-inflammatory transcripts such as TNF-alpha. Much less is known about the other family members, and none have been studied in the context of infection. Using macrophage cell lines and primary alveolar macrophages we demonstrated that, like ZFP36, ZFP36L1 is prominently induced by infection. To test our hypothesis that macrophage production of ZFP36L1 is necessary for regulation of the inflammatory response of the lung during pneumonia, we generated mice with a myeloid-specific deficiency of ZFP36L1. Surprisingly, we found that myeloid deficiency of ZFP36L1 did not result in alteration of lung cytokine production after infection, altered clearance of bacteria, or increased inflammatory lung injury. Although alveolar macrophages are critical components of the innate defense against respiratory pathogens, we concluded that myeloid ZFP36L1 is not essential for appropriate responses to bacteria in the lungs. Based on studies conducted with myeloid-deficient ZFP36 mice, our data indicate that, of the Zfp36 family, ZFP36 is the predominant negative regulator of cytokine expression in macrophages. In conclusion, these results imply that myeloid ZFP36 may fully compensate for loss of ZFP36L1 or that Zfp36l1-dependent mRNA expression does not play an integral role in the host defense against bacterial pneumonia.
C1 [Hyatt, Lynnae D.; Wasserman, Gregory A.; Rah, Yoon J.; Matsuura, Kori Y.; Coleman, Fadie T.; Hilliard, Kristie L.; Pepper-Cunningham, Zachary Ash; Ieong, Michael; Quinton, Lee J.; Mizgerd, Joseph P.; Jones, Matthew R.] Boston Univ, Sch Med, Ctr Pulm, Boston, MA 02118 USA.
[Hyatt, Lynnae D.; Ieong, Michael; Quinton, Lee J.; Mizgerd, Joseph P.; Jones, Matthew R.] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA.
[Wasserman, Gregory A.; Coleman, Fadie T.; Hilliard, Kristie L.; Mizgerd, Joseph P.] Boston Univ, Sch Med, Dept Microbiol, Boston, MA 02118 USA.
[Stumpo, Deborah J.; Blackshear, Perry J.] NIEHS, Lab Signal Transduct, NIH, Res Triangle Pk, NC 27709 USA.
[Blackshear, Perry J.] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA.
[Blackshear, Perry J.] Duke Univ, Med Ctr, Dept Biochem, Durham, NC 27710 USA.
[Quinton, Lee J.] Boston Univ, Sch Med, Dept Pathol & Lab Med, Boston, MA 02118 USA.
[Mizgerd, Joseph P.] Boston Univ, Sch Med, Dept Biochem, Boston, MA 02118 USA.
RP Jones, MR (reprint author), Boston Univ, Sch Med, Ctr Pulm, Boston, MA 02118 USA.
EM mattj@bu.edu
OI Wasserman, Gregory/0000-0002-0136-272X
FU NIH [R00-HL092956, R01-HL111449, T32-HL007035, R01-HL068153,
R01-HL079392, R01-HL104053]
FX This study was funded by NIH grants, R00-HL092956 (LJQ), R01-HL111449
(LJQ), T32-HL007035 (for LDH), R01-HL068153 (JPM), R01-HL079392 (JPM),
and R01-HL104053 (MRJ). The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 67
TC 2
Z9 2
U1 0
U2 1
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD OCT 9
PY 2014
VL 9
IS 10
AR e109072
DI 10.1371/journal.pone.0109072
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AS0AP
UT WOS:000343941200034
PM 25299049
ER
PT J
AU Raft, S
Coate, TM
Kelley, MW
Crenshaw, EB
Wu, DK
AF Raft, Steven
Coate, Thomas M.
Kelley, Matthew W.
Crenshaw, E. Bryan, III
Wu, Doris K.
TI Pou3f4-Mediated Regulation of Ephrin-B2 Controls Temporal Bone
Development in the Mouse
SO PLOS ONE
LA English
DT Article
ID PROGRESSIVE MIXED DEAFNESS; CONDUCTIVE HEARING-LOSS; X-LINKED DEAFNESS;
INNER-EAR; PERILYMPHATIC GUSHER; CELL-PROLIFERATION; OTIC CAPSULE;
MIDDLE-EAR; GENE-EXPRESSION; JOINT FORMATION
AB The temporal bone encases conductive and sensorineural elements of the ear. Mutations of POU3F4 are associated with unique temporal bone abnormalities and X-linked mixed deafness (DFNX2/DFN3). However, the target genes and developmental processes controlled by POU3F4 transcription factor activity have remained largely uncharacterized. Ephrin-B2 (Efnb2) is a signaling molecule with well-documented effects on cell adhesion, proliferation, and migration. Our analyses of targeted mouse mutants revealed that Efnb2 loss-of-function phenocopies temporal bone abnormalities of Pou3f4 hemizygous null neonates: qualitatively identical malformations of the stapes, styloid process, internal auditory canal, and cochlear capsule were present in both mutants. Using failed/insufficient separation of the stapes and styloid process as a quantitative trait, we found that single gene Efnb2 loss-of-function and compound Pou3f4/Efnb2 loss-of-function caused a more severe phenotype than single gene Pou3f4 loss-of-function. Pou3f4 and Efnb2 gene expression domains overlapped at the site of impending stapes-styloid process separation and at subcapsular mesenchyme surrounding the cochlea; at both these sites, Efnb2 expression was attenuated in Pou3f4 hemizygous null mutants relative to control. Results of immunoprecipitation experiments using chromatin isolated from nascent middle ear mesenchyme supported the hypothesis of a physical association between Pou3f4 and specific non-coding sequence of Efnb2. We propose that Efnb2 is a target of Pou3f4 transcription factor activity and an effector of mesenchymal patterning during temporal bone development.
C1 [Raft, Steven; Wu, Doris K.] NIDCD, Sect Sensory Cell Regenerat & Dev, NIH, Bethesda, MD 20892 USA.
[Coate, Thomas M.; Kelley, Matthew W.] NIDCD, Lab Cochlear Dev, NIH, Bethesda, MD USA.
[Crenshaw, E. Bryan, III] Univ Penn, Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA.
RP Raft, S (reprint author), NIDCD, Sect Sensory Cell Regenerat & Dev, NIH, Bethesda, MD 20892 USA.
EM rafts@nidcd.nih.gov; wud@nidcd.nih.gov
FU Intramural Program of the National Institute on Deafness and Other
Communication Disorders
FX Work was funded by the Intramural Program of the National Institute on
Deafness and Other Communication Disorders. The funders had no role in
study design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 69
TC 3
Z9 3
U1 1
U2 7
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD OCT 9
PY 2014
VL 9
IS 10
AR e109043
DI 10.1371/journal.pone.0109043
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AS0AP
UT WOS:000343941200031
PM 25299585
ER
PT J
AU Fasina, FO
Shittu, A
Lazarus, D
Tomori, O
Simonsen, L
Viboud, C
Chowell, G
AF Fasina, F. O.
Shittu, A.
Lazarus, D.
Tomori, O.
Simonsen, L.
Viboud, C.
Chowell, G.
TI Transmission dynamics and control of Ebola virus disease outbreak in
Nigeria, July to September 2014
SO EUROSURVEILLANCE
LA English
DT Article
ID HEMORRHAGIC-FEVER; CONGO
AB We analyse up-to-date epidemiological data of the Ebola virus disease outbreak in Nigeria as of 1 October 2014 in order to estimate the case fatality rate, the proportion of healthcare workers infected and the transmission tree. We also model the impact of control interventions on the size of the epidemic. Results indicate that Nigeria's quick and forceful implementation of control interventions was determinant in controlling the outbreak rapidly and avoiding a far worse scenario in this country.
C1 [Fasina, F. O.] Univ Pretoria, Dept Prod Anim Studies, ZA-0002 Pretoria, South Africa.
[Shittu, A.] Usmanu Danfodiyo Univ, Fac Vet Med, Dept Theriogenol & Anim Prod, Sokoto, Nigeria.
[Lazarus, D.] Natl Inst Vet Res, Viral Res Div, Vom, Plateau State, Nigeria.
[Tomori, O.] Nigerian Acad Sci, Lagos, Nigeria.
[Simonsen, L.] George Washington Univ, Milken Inst Sch Publ Hlth, Dept Global Hlth, Washington, DC USA.
[Simonsen, L.; Viboud, C.; Chowell, G.] NIH, Fogarty Int Ctr, Div Int Epidemiol & Populat Studies, Bethesda, MD 20892 USA.
[Chowell, G.] Arizona State Univ, Coll Liberal Arts & Sci, Sch Human Evolut & Social Change, Tempe, AZ USA.
RP Fasina, FO (reprint author), Univ Pretoria, Dept Prod Anim Studies, ZA-0002 Pretoria, South Africa.
EM daydupe2003@yahoo.co.uk
RI Lazarus, David/J-3631-2013
OI Lazarus, David/0000-0001-5683-7887
FU Lundbeck Foundation; Research And Policy for Infectious Disease Dynamics
program (RAPIDD) of the United States Department of Homeland Security;
Office of Pandemics and Emerging Threats at the United States Department
of Health and Human Services; NSF as part of the joint NSF-NIH-USDA
Ecology and Evolution of Infectious Diseases programme, United Kingdom
Biotechnology and Biological Sciences Research Council grant
[BB/M008894/1, 1318788, 1414374]; Division of International Epidemiology
and Population Studies, The Fogarty International Center, United States
National Institutes of Health
FX We wish to thank the Federal Ministry of Health, Abuja, Nigeria, and the
staff of the Ebola Emergency Centre who coordinated the management of
cases, containment of outbreaks and treatment protocols in Nigeria. We
would like to acknowledge the Lundbeck Foundation and the Research And
Policy for Infectious Disease Dynamics program (RAPIDD) of the United
States Department of Homeland Security for sponsorship of LS; we thank
Professor Iruka Okeke of Haverford College, PA, United States, for
sharing some initial critical data with us. CV and GC acknowledge the
financial support from the Division of International Epidemiology and
Population Studies, The Fogarty International Center, United States
National Institutes of Health, funded in part by the Office of Pandemics
and Emerging Threats at the United States Department of Health and Human
Services. GC also acknowledges support from grant NSF grant 1414374 as
part of the joint NSF-NIH-USDA Ecology and Evolution of Infectious
Diseases programme, United Kingdom Biotechnology and Biological Sciences
Research Council grant BB/M008894/1 and grant number 1318788. III:
Small: Data Management for Real-Time Data Driven Epidemic simulation.
NR 23
TC 36
Z9 36
U1 0
U2 33
PU EUR CENTRE DIS PREVENTION & CONTROL
PI STOCKHOLM
PA TOMTEBODAVAGEN 11A, STOCKHOLM, 171 83, SWEDEN
SN 1560-7917
J9 EUROSURVEILLANCE
JI Eurosurveillance
PD OCT 9
PY 2014
VL 19
IS 40
BP 11
EP 17
AR UNSP 20920
PG 7
WC Infectious Diseases
SC Infectious Diseases
GA AR7MS
UT WOS:000343764500003
PM 25323076
ER
PT J
AU Smith, OK
Aladjem, MI
AF Smith, Owen K.
Aladjem, Mirit I.
TI Chromatin Structure and Replication Origins: Determinants of Chromosome
Replication and Nuclear Organization
SO JOURNAL OF MOLECULAR BIOLOGY
LA English
DT Review
ID BETA-GLOBIN LOCUS; DIHYDROFOLATE-REDUCTASE ORIGIN; XENOPUS EGG EXTRACTS;
DNA-REPLICATION; CHINESE-HAMSTER; MAMMALIAN-CELLS; HUMAN GENOME;
TOPOLOGICAL DOMAINS; FORK PROGRESSION; TIMING PROGRAM
AB The DNA replication program is, in part, determined by the epigenetic landscape that governs local chromosome architecture and directs chromosome duplication. Replication must coordinate with other biochemical processes occurring concomitantly on chromatin, such as transcription and remodeling, to insure accurate duplication of both genetic and epigenetic features and to preserve genomic stability. The importance of genome architecture and chromatin looping in coordinating cellular processes on chromatin is illustrated by two recent sets of discoveries. First, chromatin-associated proteins that are not part of the core replication machinery were shown to affect the timing of DNA replication. These chromatin-associated proteins could be working in concert, or perhaps in competition, with the transcriptional machinery and with chromatin modifiers to determine the spatial and temporal organization of replication initiation events. Second, epigenetic interactions are mediated by DNA sequences that determine chromosomal replication. In this review, we summarize recent findings and current models linking spatial and temporal regulation of the replication program with epigenetic signaling. We discuss these issues in the context of the genome's three-dimensional structure with an emphasis on events occurring during the initiation of DNA replication. Published by Elsevier Ltd.
C1 [Smith, Owen K.; Aladjem, Mirit I.] NCI, DNA Replicat Grp, Dev Therapeut Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA.
RP Aladjem, MI (reprint author), NCI, DNA Replicat Grp, Mol Pharmacol Lab, Ctr Canc Res,NIH, Room 5056,Bldg 37,37 Convent Dr, Bethesda, MD 20892 USA.
EM aladjemm@mail.nih.gov
RI Aladjem, Mirit/G-2169-2010
OI Aladjem, Mirit/0000-0002-1875-3110
FU intramural program of the Center for Cancer Research, National Cancer
Institute, National Institutes of Health
FX We wish to thank Dr. Haiqing Fu for critical reading of the manuscript,
Dr. Eric Bouhassira for helpful discussions, and Alan Hoofring for
expert graphical assistance. Our studies were supported by the
intramural program of the Center for Cancer Research, National Cancer
Institute, National Institutes of Health.
NR 121
TC 10
Z9 10
U1 1
U2 24
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 OCT 9
PY 2014
VL 426
IS 20
SI SI
BP 3330
EP 3341
DI 10.1016/j.jmb.2014.05.027
PG 12
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA AR5IC
UT WOS:000343617400002
PM 24905010
ER
PT J
AU Dowen, JM
Fan, ZP
Hnisz, D
Ren, G
Abraham, BJ
Zhang, LN
Weintraub, AS
Schuijers, J
Lee, TI
Zhao, KJ
Young, RA
AF Dowen, Jill M.
Fan, Zi Peng
Hnisz, Denes
Ren, Gang
Abraham, Brian J.
Zhang, Lyndon N.
Weintraub, Abraham S.
Schuijers, Jurian
Lee, Tong Ihn
Zhao, Keji
Young, Richard A.
TI Control of Cell Identity Genes Occurs in Insulated Neighborhoods in
Mammalian Chromosomes
SO CELL
LA English
DT Article
ID EMBRYONIC STEM-CELLS; TRANSCRIPTIONAL REGULATION; CHROMATIN
INTERACTIONS; GENOME ORGANIZATION; DEVELOPMENTAL REGULATORS;
DROSOPHILA-MELANOGASTER; PLURIPOTENCY FACTORS; TOPOLOGICAL DOMAINS;
SUPER-ENHANCERS; BINDING SITES
AB The pluripotent state of embryonic stem cells (ESCs) is produced by active transcription of genes that control cell identity and repression of genes encoding lineage-specifying developmental regulators. Here, we use ESC cohesin ChIA-PET data to identify the local chromosomal structures at both active and repressed genes across the genome. The results produce a map of enhancer-promoter interactions and reveal that super-enhancer-driven genes generally occur within chromosome structures that are formed by the looping of two interacting CTCF sites co-occupied by cohesin. These looped structures form insulated neighborhoods whose integrity is important for proper expression of local genes. We also find that repressed genes encoding lineage-specifying developmental regulators occur within insulated neighborhoods. These results provide insights into the relationship between transcriptional control of cell identity genes and control of local chromosome structure.
C1 [Dowen, Jill M.; Fan, Zi Peng; Hnisz, Denes; Abraham, Brian J.; Zhang, Lyndon N.; Weintraub, Abraham S.; Schuijers, Jurian; Lee, Tong Ihn; Young, Richard A.] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA.
[Fan, Zi Peng] MIT, Computat & Syst Biol Program, Cambridge, MA 02139 USA.
[Ren, Gang; Zhao, Keji] NHLBI, Syst Biol Ctr, NIH, Bethesda, MD 20892 USA.
[Ren, Gang] Northwest A&F Univ, Coll Anim Sci & Technol, Yangling 712100, Shaanxi, Peoples R China.
[Zhang, Lyndon N.; Weintraub, Abraham S.; Young, Richard A.] MIT, Dept Biol, Cambridge, MA 02139 USA.
RP Zhao, KJ (reprint author), NHLBI, Syst Biol Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM zhaok@nhlbi.nih.gov; young@wi.mit.edu
RI Young, Richard/F-6495-2012
OI Young, Richard/0000-0001-8855-8647
FU National Institutes of Health [HG002668]; Division of Intramural
Research, NHLBI; Ruth L. Kirschstein National Research Service Award
[CA168263-01A1]; Austrian Science Fund (FWF) [J3490]; Rubicon Fellowship
for the Life Sciences, Netherlands Organization for Scientific Research
(NWO)
FX We thank Warren Whyte for generating the H3K27me3 ChIP-seq data set,
Chikdu Shivalila for help with genome editing experiments, Alla Sigova
for help with experiment design, Rudolf Jaenisch for sharing CRISPR
reagents, and the Whitehead Institute Genome Technology Core and NHLBI
DNA Sequencing Core for Illumina sequencing. We also thank members of
the Young lab for helpful discussions. This work was supported by the
National Institutes of Health grant HG002668 (R.A.Y.), Division of
Intramural Research, NHLBI (K.Z.), a Ruth L. Kirschstein National
Research Service Award (CA168263-01A1) (J.M.D.), an Erwin Schrodinger
Fellowship (J3490) from the Austrian Science Fund (FWF) (D.H.), and a
Rubicon Fellowship for the Life Sciences, Netherlands Organization for
Scientific Research (NWO) (J.S.). R.A.Y. is a founder of Syros
Pharmaceuticals.
NR 69
TC 155
Z9 159
U1 3
U2 55
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0092-8674
EI 1097-4172
J9 CELL
JI Cell
PD OCT 9
PY 2014
VL 159
IS 2
BP 374
EP 387
DI 10.1016/j.cell.2014.09.030
PG 14
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA AQ8QU
UT WOS:000343095600018
PM 25303531
ER
PT J
AU Andreoli, M
Persico, M
Kumar, A
Orteca, N
Kumar, V
Pepe, A
Mahalingam, S
Alegria, AE
Petrella, L
Sevciunaite, L
Camperchioli, A
Mariani, M
Di Dato, A
Novellino, E
Scambia, G
Malhotra, SV
Ferlini, C
Fattorusso, C
AF Andreoli, Mirko
Persico, Marco
Kumar, Ajay
Orteca, Nausicaa
Kumar, Vineet
Pepe, Antonella
Mahalingam, Sakkarapalayam
Alegria, Antonio E.
Petrella, Lelia
Sevciunaite, Laima
Camperchioli, Alessia
Mariani, Marisa
Di Dato, Antonio
Novellino, Ettore
Scambia, Giovanni
Malhotra, Sanjay V.
Ferlini, Cristiano
Fattorusso, Caterina
TI Identification of the First Inhibitor of the GBP1:PIM1 Interaction.
Implications for the Development of a New Class of Anticancer Agents
against Paclitaxel Resistant Cancer Cells
SO JOURNAL OF MEDICINAL CHEMISTRY
LA English
DT Article
ID III BETA-TUBULIN; GUANYLATE-BINDING PROTEIN-1; SMALL-MOLECULE
INHIBITORS; BIOLOGICAL EVALUATION; THERAPEUTIC TARGETS; LIGAND-BINDING;
PODOPHYLLOTOXIN; DERIVATIVES; DRUGS; MECHANISM
AB Class III beta-tubulin plays a prominent role in the development of drug resistance to paclitaxel by allowing the incorporation of the GBP1 GTPase into microtubules. Once in the cytoskeleton. GBP1 binds to prosurvival kinases such as PIM1 and initiates a signaling pathway that induces resistance to paclitaxel. Therefore, the inhibition of the GBP1:PIM1 interaction could potentially revert resistance to paclitaxel. A panel of 44 4-azapodophyllotoxin. derivatives was screened in the NCI-60 cell panel. The result is that 31 are active and the comparative analysis demonstrated specific activity in paclitax el-resistant cells, Using surface plasmon resonance, we were able to prove that NSC756093 is a potent in vitro inhibitor of the GBP1:PIM1 interaction and that this property is maintained in vivo in ovarian cancer cells resistant to paclitaxel. Through bioinformatics, molecular modeling and mutagenesis studies, we identified the putative NSC756093 binding site at the interface between the helical and the LG domain of GBP1. According to our results by binding to this site the NSC756093 compound is able to stabilize a conformation of GBP1 not suitable for binding to PIM1.
C1 [Andreoli, Mirko; Mariani, Marisa; Ferlini, Cristiano] Danbury Hosp Res Inst, Danbury, CT 06810 USA.
[Persico, Marco; Orteca, Nausicaa; Di Dato, Antonio; Novellino, Ettore; Fattorusso, Caterina] Univ Naples Federico II, Dept Pharm, I-80131 Naples, Italy.
[Kumar, Vineet; Pepe, Antonella; Malhotra, Sanjay V.] Leidos Biomed Res Inc, Lab Synthet Chem, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
[Kumar, Ajay] Univ Metropolitana, Sch Environm Affairs, San Juan, PR 00928 USA.
[Alegria, Antonio E.] Univ Puerto Rico, Dept Chem, Humacao, PR 00791 USA.
[Petrella, Lelia; Sevciunaite, Laima; Camperchioli, Alessia] Jean Paul IInd Res Fdn, Mol Oncol Lab, I-86100 Campobasso, Italy.
[Scambia, Giovanni] Univ Cattolica Sacro Cuore, Dept Obstet & Gynecol, I-00168 Rome, Italy.
[Mahalingam, Sakkarapalayam] Purdue Univ, Dept Chem, W Lafayette, IN 47907 USA.
RP Fattorusso, C (reprint author), Univ Naples Federico II, Dept Pharm, Via D Montesano 49, I-80131 Naples, Italy.
EM malhotrasa@mail.nih.gov; cristiano.ferlini@danhosp.org;
caterina.fattorusso@unina.it
RI fattorusso, caterina/F-7113-2015; Persico, Marco/L-8448-2014
OI fattorusso, caterina/0000-0003-3330-4281; Di Dato,
Antonio/0000-0002-3463-367X; Camperchioli, Alessia/0000-0002-4407-4613;
Persico, Marco/0000-0003-0010-0338
FU National Cancer Institute, National Institutes of Health
[HHSN261200800001E]; National Center for Research Resources; National
Institute of General Medical Sciences of the National Institutes of
Health [8 P20 GM 103475]; Connecticut State [2014-0908]; liberal
donation from Rudy and Sally Ruggles; Associazione Oppo e le sue stanze
ONLUS; EU project Bluegenics [311848]; Italian MIUR [FIRB
RBFR12WB3W_003]
FX We thank the NCI Developmental Therapeutics Program for 60 cell line
screening. We also thank Robert Bedoukian for his advice. The study was
partially supported by the National Cancer Institute, National
Institutes of Health, under contract no. HHSN261200800001E (S.V.M.,
A.P., and V.K.), by the National Center for Research Resources and the
National Institute of General Medical Sciences of the National
Institutes of Health through grant no. 8 P20 GM 103475 (A.K.), by the
Connecticut State Grant 2014-0908 (C.Fe.), by a liberal donation from
Rudy and Sally Ruggles (C.Fe.), by the Associazione Oppo e le sue stanze
ONLUS (G.S.), by the EU project Bluegenics grant 311848 (C.F.), and by
the Italian MIUR financial FIRB RBFR12WB3W_003 (M.P). Sponsors of the
research were not involved in the design and interpretation of the
experimental activities.
NR 41
TC 10
Z9 10
U1 0
U2 26
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 OCT 9
PY 2014
VL 57
IS 19
BP 7916
EP 7932
DI 10.1021/jm50099021
PG 17
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA AQ7RG
UT WOS:000343016300008
PM 25211704
ER
PT J
AU Wang, CN
Schroeder, FA
Wey, HY
Borra, R
Wagner, FF
Reis, S
Kim, SW
Holson, EB
Haggarty, SJ
Hooker, JM
AF Wang, Changning
Schroeder, Frederick A.
Wey, Hsiao-Ying
Borra, Ronald
Wagner, Florence F.
Reis, Surya
Kim, Sung Won
Holson, Edward B.
Haggarty, Stephen J.
Hooker, Jacob M.
TI In Vivo Imaging of Histone Deacetylases (HDACs) in the Central Nervous
System and Major Peripheral Organs
SO JOURNAL OF MEDICINAL CHEMISTRY
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; BRAIN; PET; INHIBITORS; DISEASE;
OVEREXPRESSION; CANCER; RADIOLIGANDS; ACETYLATION; HYPERTROPHY
AB Epigenetic enzymes are now targeted to treat the underlying gene expression dysregulation that contribute to disease pathogenesis. Histone deacetylases (HDACs) have shown broad potential in treatments against cancer and emerging data supports their targeting in the context of cardiovascular disease and central nervous system dysfunciton Development of a molecular agent for non-invasive imaing to elucidate the distribution and functional role of HDACs in humans will accelerate medical research and drug discovery in this domain. Herein, we describe the synthesis and validation of an HDAC imaging agent, [C-11]6. Our imaging results demonstrate that this probe has high specificity, good selectivity, and appropriate kinetics and distribution for imaging HDACs in the brian, heart, kidney, pancreas. and spleen. Our findings support the translational potential for [C-11]6 for human epigenetic imaging.
C1 [Wang, Changning; Schroeder, Frederick A.; Wey, Hsiao-Ying; Borra, Ronald; Hooker, Jacob M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Athinoula A Martinos Ctr Biomed Imaging,Dept Radi, Charlestown, MA 02129 USA.
[Schroeder, Frederick A.; Reis, Surya; Haggarty, Stephen J.] Massachusetts Gen Hosp, Ctr Human Genet Res, Chem Neurobiol Lab, Dept Neurol, Boston, MA 02114 USA.
[Schroeder, Frederick A.; Reis, Surya; Haggarty, Stephen J.] Massachusetts Gen Hosp, Ctr Human Genet Res, Chem Neurobiol Lab, Dept Psychiat, Boston, MA 02114 USA.
[Wagner, Florence F.; Holson, Edward B.] Broad Inst Harvard & MIT, Stanley Ctr Psychiat Res, Cambridge Ctr 7, Cambridge, MA 02142 USA.
[Kim, Sung Won] NIAAA, Lab Neuroimaging, Bethesda, MD 20892 USA.
RP Hooker, JM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Athinoula A Martinos Ctr Biomed Imaging,Dept Radi, 73 High St, Charlestown, MA 02129 USA.
EM hooker@nmr.mgh.harvard.edu
OI Haggarty, Stephen J./0000-0002-7872-168X
FU Harvard/MGH Nuclear Medicine Training Program from the Department of
Energy [DE-SC0008430]; National Institute of Drug Abuse (NIDA) of the
National Institutes of Health [R01DA030321, R01DA028301]; National
Institute of Biomedical Imaging and Bioengineering (NIBIB); National
Institutes of Health; NIH [S10RR017208, S10RR026666, S10RR022976,
S10RR019933, S10RR029495]
FX C.W. and H.Y.W. are supported by the Harvard/MGH Nuclear Medicine
Training Program from the Department of Energy (DE-SC0008430). Research
was supported by the National Institute of Drug Abuse (NIDA) of the
National Institutes of Health under grant numbers R01DA030321 (J.M.H.;
SJ.H) with additional support under grant R01DA028301 (SJ.H.). This
research was carried out at the Athinoula A. Martinos Center for
Biomedical Imaging at the Massachusetts General Hospital, using
resources provided by the Center for Functional Neuroirnaging
Technologies, P41EB015896, a P41 Regional Resource supported by the
National Institute of Biomedical Imaging and Bioengineering (NIBIB),
National Institutes of Health. This work also involved the use of
instrumentation supported by the NIH Shared Instrumentation Grant
Program and/or High-End Instrumentation Grant Program; specifically,
grant nos: S10RR017208, S10RR026666, S10RR022976, S10RR019933, and
S10RR029495. The authors are grateful to Joe Mandeville and Helen Deng
as well as the Martinos Center radiopharmacy and imaging staff (Grae
Arabasz, Shirley Hsu, Stephen Carlin, Chris Moseley, Nathan Schauer,
Ehimen Aisaborhale, Judit Sore) for help with nonhuman primate
experiments. HDAC activity screening was enabled by a Caliper assay
developed by Jennifer Gale and Yan-Ling Zhang at the Broad Institute.
NR 45
TC 13
Z9 13
U1 6
U2 19
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0022-2623
EI 1520-4804
J9 J MED CHEM
JI J. Med. Chem.
PD OCT 9
PY 2014
VL 57
IS 19
BP 7999
EP 8009
DI 10.1021/jm500872
PG 11
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA AQ7RG
UT WOS:000343016300015
PM 25203558
ER
PT J
AU Dexheimer, TS
Rosenthal, AS
Luci, DK
Liang, Q
Villamil, MA
Chen, JJ
Sun, HM
Kerns, EH
Simeonov, A
Jadhav, A
Zhuang, ZH
Maloney, DJ
AF Dexheimer, Thomas S.
Rosenthal, Andrew S.
Luci, Diane K.
Liang, Qin
Villamil, Mark A.
Chen, Junjun
Sun, Hongmao
Kerns, Edward H.
Simeonov, Anton
Jadhav, Ajit
Zhuang, Zhihao
Maloney, David J.
TI Synthesis and Structure-Activity Relationship Studies of
N-Benzyl-2-phenylpyrimidin-4-amine Derivatives as Potent USP1/UAF1
Deubiquitinase Inhibitors with Anticancer Activity against Nonsmall Cell
Lung Cancer
SO JOURNAL OF MEDICINAL CHEMISTRY
LA English
DT Article
ID FANCONI-ANEMIA PATHWAY; EMERGING ROLES; DRUG TARGETS; ID PROTEINS;
UBIQUITIN; ENZYMES; IDENTIFICATION; MECHANISMS; SYSTEM; REPAIR
AB Deregulation of ubiquitin conjugation or deconjugation has been implicated in the pathogenesis of many human diseases. including cancer. The deubiquitinating enzyme USP1 (ubiquitin-specific protease 1), in association with UAF1 (USP1 further evaluate USP1/UAF1 as a therapeutic target, we conducted a quantitative high throughput screen of >400000 compounds and subsequent medicinal chemistry optimization of small molecules that inhibit the deubiquitinating activity of USP1/UAF1 ultimately, these efforts led to the identification of ML323 (70) and related N-benzyl-2-phenylprimidin-4-amine derivatives, which possess nanomolar USP1/UAF1 inhibitory potency. Moreover, we demonstrate a strong correlation between compund IC50 values for USP1/UAF1 inhibiton and activity in nonsmall cell lung cancer cells, specifically increased monoubiquitinated PCNA (Ub-PCNA) levels and decreased cell survival. Our results establish the druggability of the USP1/UAF1 deubiquitinase complex and its potential as a molecualr target for anticancer therapies
C1 [Dexheimer, Thomas S.; Rosenthal, Andrew S.; Luci, Diane K.; Sun, Hongmao; Kerns, Edward H.; Simeonov, Anton; Jadhav, Ajit; Maloney, David J.] NIH, Natl Ctr Advancing Translat Sci, Rockville, MD 20850 USA.
[Liang, Qin; Villamil, Mark A.; Chen, Junjun; Zhuang, Zhihao] Univ Delaware, Dept Chem & Biochem, Newark, DE 19716 USA.
RP Maloney, DJ (reprint author), NIH, Natl Ctr Advancing Translat Sci, 9800 Med Ctr, Rockville, MD 20850 USA.
EM zzhuang@udel.edu; maloneyd@mail.nih.gov
RI liang, qin/C-8284-2016
FU U.S. National Institutes of Health (NIH) [R03DA030552, R0IGM097468];
intramural research program of the National Center for Advancing
Translational Sciences; Molecular Libraries Initiative of the National
Institutes of Health Roadmap for Medical Research [U54MH084681]
FX This work was supported in part by U.S. National Institutes of Health
(NIH) grants R03DA030552 and R0IGM097468 to Z.Z. T.S.D., A.S.R, D.K.L.,
E.H.K., A.S., A.J., and D.J.M. were supported by the intramural research
program of the National Center for Advancing Translational Sciences and
the Molecular Libraries Initiative of the National Institutes of Health
Roadmap for Medical Research (U54MH084681). We thank Sam Michael and
Richard Jones for automation support, Paul Shinn Misha Itkin, and
Danielle van Leer for the assistance with compound management, William
Leister, Heather Baker, Elizabeth Fernandez, and Christopher Leclair for
analytical chemistry and purification support, and Kimloan Nguyen for in
vitro ADME data.
NR 35
TC 13
Z9 13
U1 1
U2 20
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 OCT 9
PY 2014
VL 57
IS 19
BP 8099
EP 8110
DI 10.1021/jm5010495
PG 12
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA AQ7RG
UT WOS:000343016300022
PM 25229643
ER
PT J
AU Olfson, M
Schoenbaum, M
AF Olfson, Mark
Schoenbaum, Michael
TI Link between FDA antidepressant warnings and increased suicide attempts
in young people is questionable
SO BMJ-BRITISH MEDICAL JOURNAL
LA English
DT Letter
ID BEHAVIOR
C1 [Olfson, Mark] Columbia Univ, Med Ctr, New York, NY 10032 USA.
[Schoenbaum, Michael] NIH, Bethesda, MD 20892 USA.
RP Olfson, M (reprint author), Columbia Univ, Med Ctr, New York, NY 10032 USA.
EM mo49@columbia.edu
NR 6
TC 1
Z9 1
U1 2
U2 2
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 1756-1833
J9 BMJ-BRIT MED J
JI BMJ-British Medical Journal
PD OCT 9
PY 2014
VL 349
AR g5614
DI 10.1136/bmj.g5614
PG 1
WC Medicine, General & Internal
SC General & Internal Medicine
GA AQ7LK
UT WOS:000342998200001
PM 25301267
ER
PT J
AU Feldmann, H
AF Feldmann, Heinz
TI Ebola - A Growing Threat?
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Editorial Material
C1 NIAID, Rocky Mt Labs, Virol Lab, Div Intramural Res, Hamilton, MT 59840 USA.
RP Feldmann, H (reprint author), NIAID, Rocky Mt Labs, Virol Lab, Div Intramural Res, Hamilton, MT 59840 USA.
NR 5
TC 34
Z9 40
U1 0
U2 61
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 OCT 9
PY 2014
VL 371
IS 15
BP 1375
EP 1378
DI 10.1056/NEJMp1405314
PG 4
WC Medicine, General & Internal
SC General & Internal Medicine
GA AQ3FJ
UT WOS:000342674800005
PM 24805988
ER
PT J
AU Guardado-Estrada, M
Juarez-Torres, E
Roman-Bassaure, E
Medina-Martinez, I
Alfaro, A
Benuto, RE
Dean, M
Villegas-Sepulveda, N
Berumen, J
AF Guardado-Estrada, Mariano
Juarez-Torres, Eligia
Roman-Bassaure, Edgar
Medina-Martinez, Ingrid
Alfaro, Ana
Elba Benuto, Rosa
Dean, Michael
Villegas-Sepulveda, Nicolas
Berumen, Jaime
TI The Distribution of High-Risk Human Papillomaviruses Is Different in
Young and Old Patients with Cervical Cancer
SO PLOS ONE
LA English
DT Article
ID GENITAL HUMAN PAPILLOMAVIRUSES; INTRAEPITHELIAL NEOPLASIA; INFECTION;
WOMEN; LESIONS; AMPLIFICATION; METAANALYSIS; PREVALENCE; CYTOLOGY;
HUMAN-PAPILLOMAVIRUS-16
AB Despite numerous human papillomavirus (HPV) frequency studies in women with cervical cancer (CC), little is known of HPV frequency trends according to patient age. In this work, we compare the mean age and frequency distribution by age of CC patients positive for different HPVs. This study included 462 CC patients. HPVs were detected by PCR and typed using DNA sequencing. A total of 456 patients (98.7%) were positive for HPV: 418 (90.5%) had single and 38 (8.2%) had double HPV infections. HPV16 (46.5%), HPV18 (10.4%), HPV45 (6.7%), and HPV31 (4.1%) were the most frequent viral types in single-infected patients. The mean ages of single-infected patients with HPV16 (49.2 +/- 13.3), HPV18 (47.9 +/- 12.2), HPV45 (47.9 +/- 11.7), or HPV39 (42.6 +/- 8.9) were significantly lower than the mean ages of patients singly (53.9 +/- 12.7; p<0.001, t-test) or doubly (55.4 +/- 12.7; p<0.05, t-test) infected with the remaining HPVs. Three different trends were identified: one for HPV16, another for HPVs18/45/39, and a third for the rest of HPVs. The frequency trend of HPV16 shows two peaks. The first (63.2%) was found in the youngest women (<= 35 years), followed by a decreasing trend until the age of 5560 years (31.1%). The second peak arose at 6165 years (52.5%), followed by a decreasing trend. The trend for HPVs18/45/39 declined from the youngest (19.3%) to the oldest (>70 years; 12.8%) women. In contrast, the trend for the remaining HPVs increased from the youngest (15.8%) to the oldest (46.2%) women. Unlike other life-style factors, low-risk sexual behavior was associated with late onset of CC independent of low-oncogenic HPV types (p<0.05, Wald chi-square statistic). The data indicate that most CCs in young women depend on the presence of high-oncogenic HPVs. In contrast, almost half of CCs in older patients had low-oncogenic HPVs, suggesting they could depend on the presence of other factors.
C1 [Guardado-Estrada, Mariano; Juarez-Torres, Eligia; Medina-Martinez, Ingrid; Alfaro, Ana; Berumen, Jaime] Univ Nacl Autonoma Mexico, Hosp Gen Mexico, Fac Med, Unidad Med, Mexico City 04510, DF, Mexico.
[Roman-Bassaure, Edgar] Hosp Gen Mexico City, Serv Oncol, Mexico City, DF, Mexico.
[Elba Benuto, Rosa] Acad Mexicana Dermatol, Mexico City, DF, Mexico.
[Dean, Michael] NCI, Expt Immunol Lab, Frederick, MD 21701 USA.
[Villegas-Sepulveda, Nicolas] Inst Politecn Nacl, Ctr Invest & Estudios Avanzados, Dept Biomed Mol, Mexico City, DF, Mexico.
[Berumen, Jaime] Univ Nacl Autonoma Mexico, Fac Med, Dept Expt Med, Mexico City 04510, DF, Mexico.
RP Berumen, J (reprint author), Univ Nacl Autonoma Mexico, Hosp Gen Mexico, Fac Med, Unidad Med, Mexico City 04510, DF, Mexico.
EM jaimeberumen@hotmail.com
OI Villegas-Sepulveda, Nicolas/0000-0001-9489-2545
FU National Council of Science and Technology (CONACYT) [8135/A1, 24341];
National University of Mexico [SDI.PTID.05.2]
FX This work was supported by the National Council of Science and
Technology (CONACYT, www.conacyt.mx), grant numbers 8135/A1, 24341 and
the National University of Mexico (www.unam.mx), grant number
SDI.PTID.05.2. The funders had no role in study design, data collection
and analysis, decision to publish, or preparation of the manuscript.
NR 50
TC 4
Z9 4
U1 0
U2 7
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD OCT 8
PY 2014
VL 9
IS 10
AR e109406
DI 10.1371/journal.pone.0109406
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AT8TE
UT WOS:000345204000069
PM 25295590
ER
PT J
AU Pangilinan, F
Molloy, AM
Mills, JL
Troendle, JF
Parle-McDermott, A
Kay, DM
Browne, ML
McGrath, EC
Abaan, HO
Sutton, M
Kirke, PN
Caggana, M
Shane, B
Scott, JM
Brody, LC
AF Pangilinan, Faith
Molloy, Anne M.
Mills, James L.
Troendle, James F.
Parle-McDermott, Anne
Kay, Denise M.
Browne, Marilyn L.
McGrath, Emily C.
Abaan, Hatice Ozel
Sutton, Marie
Kirke, Peadar N.
Caggana, Michele
Shane, Barry
Scott, John M.
Brody, Lawrence C.
TI Replication and exploratory analysis of 24 candidate risk polymorphisms
for neural tube defects
SO BMC MEDICAL GENETICS
LA English
DT Article
DE Neural tube defects; Spina bifida; Folate; Folic acid; One-carbon
metabolism; Replication
ID DIHYDROFOLATE-REDUCTASE DHFR; FOLATE-RELATED GENES; FOLIC-ACID
RECOMMENDATIONS; MTRR A66G POLYMORPHISMS; SPINA-BIFIDA;
METHYLENETETRAHYDROFOLATE REDUCTASE; METHIONINE SYNTHASE; BIRTH-DEFECTS;
MATERNAL RISK; 5,10-METHYLENETETRAHYDROFOLATE REDUCTASE
AB Background: Neural tube defects (NTDs), which are among the most common congenital malformations, are influenced by environmental and genetic factors. Low maternal folate is the strongest known contributing factor, making variants in genes in the folate metabolic pathway attractive candidates for NTD risk. Multiple studies have identified nominally significant allelic associations with NTDs. We tested whether associations detected in a large Irish cohort could be replicated in an independent population.
Methods: Replication tests of 24 nominally significant NTD associations were performed in racially/ethnically matched populations. Family-based tests of fifteen nominally significant single nucleotide polymorphisms (SNPs) were repeated in a cohort of NTD trios (530 cases and their parents) from the United Kingdom, and case-control tests of nine nominally significant SNPs were repeated in a cohort (190 cases, 941 controls) from New York State (NYS). Secondary hypotheses involved evaluating the latter set of nine SNPs for NTD association using alternate case-control models and NTD groupings in white, African American and Hispanic cohorts from NYS.
Results: Of the 24 SNPs tested for replication, ADA rs452159 and MTR rs10925260 were significantly associated with isolated NTDs. Of the secondary tests performed, ARID1A rs11247593 was associated with NTDs in whites, and ALDH1A2 rs7169289 was associated with isolated NTDs in African Americans.
Conclusions: We report a number of associations between SNP genotypes and neural tube defects. These associations were nominally significant before correction for multiple hypothesis testing. These corrections are highly conservative for association studies of untested hypotheses, and may be too conservative for replication studies. We therefore believe the true effect of these four nominally significant SNPs on NTD risk will be more definitively determined by further study in other populations, and eventual meta-analysis.
C1 [Pangilinan, Faith; Abaan, Hatice Ozel; Brody, Lawrence C.] NHGRI, Mol Pathogenesis Sect, Genome Technol Branch, NIH, Bethesda, MD 20892 USA.
[Molloy, Anne M.] Univ Dublin Trinity Coll, Dept Clin Med, Dublin 2, Ireland.
[Mills, James L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, NIH, Bethesda, MD USA.
[Troendle, James F.] NHLBI, Off Biostat Res, NIH, Bethesda, MD 20892 USA.
[Parle-McDermott, Anne] Dublin City Univ, Sch Biotechnol, Dublin 9, Ireland.
[Kay, Denise M.; McGrath, Emily C.; Caggana, Michele] New York State Dept Hlth, Wadsworth Ctr, Div Genet, Albany, NY 12201 USA.
[Browne, Marilyn L.] New York State Dept Hlth, Congenital Malformat Registry, Troy, NY 12180 USA.
[Browne, Marilyn L.] Univ Albany, Sch Publ Hlth, Dept Epidemiol & Biostat, Rensselaer, NY 12144 USA.
[Sutton, Marie] Hlth Res Board, Evidence Ctr, Dublin, Ireland.
[Kirke, Peadar N.] Hlth Res Board, Child Hlth Epidemiol Unit, Dublin, Ireland.
[Shane, Barry] Univ Calif Berkeley, Dept Nutr Sci & Toxicol, Berkeley, CA 94720 USA.
[Scott, John M.] Univ Dublin Trinity Coll, Sch Biochem & Immunol, Dublin 2, Ireland.
RP Brody, LC (reprint author), NHGRI, Mol Pathogenesis Sect, Genome Technol Branch, NIH, Room 5306,50 South Dr, Bethesda, MD 20892 USA.
EM lbrody@mail.nih.gov
OI Kay, Denise/0000-0002-9928-2698; Molloy, Anne/0000-0002-1688-9049
FU National Human Genome Research Institute; Eunice Kennedy Shriver
National Institute of Child Health and Human Development (NICHD)
[N01-DK-7-3431]; Health Research Board, Ireland
FX These studies would not be possible without the participation of the
affected families, and their recruitment by the United Kingdom
Association of Spina Bifida and Hydrocephalus. The authors acknowledge
research support from the Intramural Research programs of the National
Human Genome Research Institute, the Eunice Kennedy Shriver National
Institute of Child Health and Human Development (NICHD contract number:
N01-DK-7-3431), and the Health Research Board, Ireland. We thank Dr.
Charlotte Druschel, Director of the Congenital Malformations Registry,
for identifying and reviewing cases for this investigation, and Sandra
D. Richardson at the NYSCMR for subject selection and data management.
We also thank April J. Atkins, Adam C. Gearhart, and Robert J. Sicko at
the Wadsworth Center, New York State Department of Health for providing
laboratory and technical assistance.
NR 62
TC 4
Z9 4
U1 2
U2 8
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2350
J9 BMC MED GENET
JI BMC Med. Genet.
PD OCT 8
PY 2014
VL 15
AR 102
DI 10.1186/s12881-014-0102-9
PG 9
WC Genetics & Heredity
SC Genetics & Heredity
GA AS2IC
UT WOS:000344102200001
PM 25293959
ER
PT J
AU Sacks, D
AF Sacks, David
TI Lost but Not Forgotten
SO CELL HOST & MICROBE
LA English
DT Editorial Material
ID PARAFLAGELLAR ROD PROTEINS; TRYPANOSOMA-CRUZI; CHAGAS-DISEASE
AB During its developmental transformation in the mammalian host, Trypanosma cruzi discards it flagellum into the cytoplasm of the host cell. In the current issue of Cell Host & Microbe, Kurup and Tarleton (2014) exploit the antigens made available by this process to develop a more effective vaccine strategy.
C1 NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Sacks, D (reprint author), NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
EM dsacks@nih.gov
NR 9
TC 0
Z9 0
U1 0
U2 1
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1931-3128
EI 1934-6069
J9 CELL HOST MICROBE
JI Cell Host Microbe
PD OCT 8
PY 2014
VL 16
IS 4
BP 423
EP 425
DI 10.1016/j.chom.2014.09.017
PG 4
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA AR8LG
UT WOS:000343826100003
PM 25299325
ER
PT J
AU Jia, JM
Hu, ZH
Nordman, J
Li, Z
AF Jia, Jie-Min
Hu, Zhonghua
Nordman, Jacob
Li, Zheng
TI The Schizophrenia Susceptibility Gene Dysbindin Regulates Dendritic
Spine Dynamics
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
DE CaMKIIa; dendritic spine; dynamics; dysbindin; hippocampus;
schizophrenia
ID CORTICAL PYRAMIDAL NEURONS; HIPPOCAMPAL-FORMATION; DENSITY; COMPLEX;
PROTEIN; MATURATION; PLASTICITY; SYNAPSES; DTNBP1; BRAIN
AB Dysbindin is a schizophrenia susceptibility gene required for the development of dendritic spines. The expression of dysbindin proteins is decreased in the brains of schizophrenia patients, and neurons in mice carrying a deletion in the dysbindin gene have fewer dendritic spines. Hence, dysbindin might contribute to the spine pathology of schizophrenia, which manifests as a decrease in the number of dendritic spines. The development of dendritic spines is a dynamic process involving formation, retraction, and transformation of dendritic protrusions. It has yet to be determined whether dysbindin regulates the dynamics of dendritic protrusions. Here we address this question using time-lapse imaging in hippocampal neurons. Our results show that dysbindin is required to stabilize dendritic protrusions. In dysbindin-null neurons, dendritic protrusions are hyperactive in formation, retraction, and conversion between different types of protrusions. We further show that CaMKII alpha is required for the stabilization of mushroom/thin spines, and that the hyperactivity of dendritic protrusions in dysbindin-null neurons is attributed in part to decreased CaMKII alpha activity resulting from increased inhibition of CaMKII alpha by Abi1. These findings elucidate the function of dysbindin in the dynamic morphogenesis of dendritic protrusions, and reveal the essential roles of dysbindin and CaMKII alpha in the stabilization of dendritic protrusions during neuronal development.
C1 [Jia, Jie-Min; Hu, Zhonghua; Nordman, Jacob; Li, Zheng] NIMH, Unit Synapse Dev & Plast, NIH, Bethesda, MD 20892 USA.
RP Li, Z (reprint author), NIH, 35 Convent Dr,Room 2C1010, Bethesda, MD 20892 USA.
EM lizheng2@mail.nih.gov
RI Jia, Jie-Min/O-1150-2013; Li, Zheng/I-8016-2014; Hu,
Zhonghua/J-1169-2016
OI Jia, Jie-Min/0000-0001-8446-3819; Li, Zheng/0000-0002-2978-2531; Hu,
Zhonghua/0000-0002-0117-7081
FU NIMH Intramural Program
FX This work was supported by the NIMH Intramural Program. We thank Dr
Elizabeth J. Sherman (NIMH/NIH) for editing the paper.
NR 25
TC 8
Z9 8
U1 0
U2 9
PU SOC NEUROSCIENCE
PI WASHINGTON
PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA
SN 0270-6474
J9 J NEUROSCI
JI J. Neurosci.
PD OCT 8
PY 2014
VL 34
IS 41
BP 13725
EP 13736
DI 10.1523/JNEUROSCI.0184-14.2014
PG 12
WC Neurosciences
SC Neurosciences & Neurology
GA AQ9DF
UT WOS:000343142100015
PM 25297099
ER
PT J
AU Cummings, DM
Snyder, JS
Brewer, M
Cameron, HA
Belluscio, L
AF Cummings, Diana M.
Snyder, Jason S.
Brewer, Michelle
Cameron, Heather A.
Belluscio, Leonardo
TI Adult Neurogenesis Is Necessary to Refine and Maintain Circuit
Specificity
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
DE interneuron; intrabulbar map; neurogenesis; olfactory deprivation;
rostral migratory stream; subventricular zone
ID MOUSE OLFACTORY-BULB; INTRABULBAR ASSOCIATIONAL SYSTEM; GRANULE CELLS;
HIPPOCAMPAL NEUROGENESIS; SUBVENTRICULAR ZONE; NEWBORN NEURONS;
MAMMALIAN BRAIN; IN-VIVO; RAT; INTERNEURONS
AB The circuitry of the olfactory bulb contains a precise anatomical map that links isofunctional regions within each olfactory bulb. This intrabulbar map forms perinatally and undergoes activity-dependent refinement during the first postnatal weeks. Although this map retains its plasticity throughout adulthood, its organization is remarkably stable despite the addition of millions of new neurons to this circuit. Here we show that the continuous supply of new neuroblasts from the subventricular zone is necessary for both the restoration and maintenance of this precise central circuit. Using pharmacogenetic methods to conditionally ablate adult neurogenesis in transgenic mice, we find that the influx of neuroblasts is required for recovery of intrabulbar map precision after disruption due to sensory block. We further demonstrate that eliminating adult-born interneurons in naive animals leads to an expansion of tufted cell axons that is identical to the changes caused by sensory block, thus revealing an essential role for new neurons in circuit maintenance under baseline conditions. These findings show, for the first time, that inhibiting adult neurogenesis alters the circuitry of projection neurons in brain regions that receive new interneurons and points to a critical role for adult-born neurons in stabilizing a brain circuit that exhibits high levels of plasticity.
C1 [Cummings, Diana M.; Belluscio, Leonardo] NINDS, Dev Neural Plast Sect, NIH, Bethesda, MD 20892 USA.
[Snyder, Jason S.; Brewer, Michelle; Cameron, Heather A.] NIMH, Sect Neuroplast, NIH, Bethesda, MD 20892 USA.
RP Belluscio, L (reprint author), NINDS, Porter Neuroscience Res Ctr, Dev Neural Plast Sect, Bldg 35,Room 3E-410,35 Convent Dr,MSC 3703, Bethesda, MD 20892 USA.
EM belluscl@ninds.nih.gov
RI Cameron, Heather/E-6221-2011;
OI Cameron, Heather/0000-0002-3245-5777; Snyder, Jason/0000-0002-5509-0272
FU Intramural Research Program of the National Institutes of Health;
National Institute of Neurological Disorders and Stroke; National
Institute of Mental Health
FX This work was supported by the Intramural Research Program of the
National Institutes of Health, National Institute of Neurological
Disorders and Stroke, and the National Institute of Mental Health.
NR 48
TC 6
Z9 6
U1 0
U2 4
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 OCT 8
PY 2014
VL 34
IS 41
BP 13801
EP 13810
DI 10.1523/JNEUROSCI.2463-14.2014
PG 10
WC Neurosciences
SC Neurosciences & Neurology
GA AQ9DF
UT WOS:000343142100022
PM 25297106
ER
PT J
AU Zhou, Y
Asahara, H
Schneider, N
Dranchak, P
Inglese, J
Chong, SR
AF Zhou, Ying
Asahara, Haruichi
Schneider, Nils
Dranchak, Patricia
Inglese, James
Chong, Shaorong
TI Engineering Bacterial Transcription Regulation To Create a Synthetic in
Vitro Two-Hybrid System for Protein Interaction Assays
SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Article
ID FRAGMENT COMPLEMENTATION ASSAYS; CELL-FREE TRANSLATION; ONE-HYBRID
SYSTEM; ESCHERICHIA-COLI; RNA-POLYMERASE; ESTROGEN-RECEPTOR;
CRYSTAL-STRUCTURE; DNA RECOGNITION; BINDING; COMPLEX
AB Transcriptional activation of sigma(54)-RNA polymerase holoenzyme (sigma(54)-RNAP) in bacteria is dependent on a cis-acting DNA element (bacterial enhancer), which recruits the bacterial enhancer-binding protein to contact the holoenzyme via DNA looping. Using a constructive synthetic biology approach, we recapitulated such process of transcriptional activation by recruitment in a reconstituted cell-free system, assembled entirely from a defined number of purified components. We further engineered the bacterial enhancer-binding protein PspF to create an in vitro two-hybrid system (IVT2H), capable of carrying out gene regulation in response to expressed protein interactions. Compared with genetic systems and other in vitro methods, IVT2H not only allows detection of different types of protein interactions in just a few hours without involving cells but also provides a general correlation of the relative binding strength of the protein interaction with the IVT2H signal. Due to its reconstituted nature, IVT2H provides a biochemical assay platform with a clean and defined background. We demonstrated the proof-of-concept of using IVT2H as an alternative assay for high throughput screening of small-molecule inhibitors of protein-protein interaction.
C1 [Zhou, Ying; Asahara, Haruichi; Chong, Shaorong] New England Biolabs Inc, Ipswich, MA 01938 USA.
[Schneider, Nils] Ecole Super Biotechnol Strasbourg, F-67400 Illkirch Graffenstaden, France.
[Dranchak, Patricia; Inglese, James] NIH, Div Preclin Innovat, Natl Ctr Adv Translat Sci, Rockville, MD 20850 USA.
[Inglese, James] NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA.
RP Chong, SR (reprint author), New England Biolabs Inc, 240 Cty Rd, Ipswich, MA 01938 USA.
EM chong@neb.com
FU NIH [GM086930]; New England Biolabs; Divisions of Intramural Research at
the National Human Genome Institute; National Center for Advancing
Translational Sciences at the National Institutes of Health
FX We thank Drs. Chris Noren, Chris Taron, and Bill Jack for suggestions
and comments on the manuscript, Dr. Dongxian Yue for supplying RNA
polymerase core enzyme, G. B. Robb for suggestions of RNA binding
proteins, Dr. Ryan MacArthur for informatics support, and Drs. Richard
Roberts and Donald Comb for encouragement. This study was supported by
NIH GM086930 and New England Biolabs to S.C. and by Divisions of
Intramural Research at the National Human Genome Institute and the
National Center for Advancing Translational Sciences at the National
Institutes of Health to J.I. and P.D.
NR 54
TC 5
Z9 5
U1 3
U2 30
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 OCT 8
PY 2014
VL 136
IS 40
BP 14031
EP 14038
DI 10.1021/ja502512g
PG 8
WC Chemistry, Multidisciplinary
SC Chemistry
GA AQ7VG
UT WOS:000343026700020
PM 25188838
ER
PT J
AU Gorka, AP
Nani, RR
Zhu, JJ
Mackem, S
Schnermann, MJ
AF Gorka, Alexander P.
Nani, Roger R.
Zhu, Jianjian
Mackem, Susan
Schnermann, Martin J.
TI A Near-IR Uncaging Strategy Based on Cyanine Photochemistry
SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Article
ID PHOTO-UNCLICK CHEMISTRY; IMPROVED PHOTOSTABILITY; ORGANIC FLUOROPHORES;
VISIBLE-LIGHT; IN-VITRO; DYES; BIOLOGY; CELLS; PHOTOOXIDATION;
CHROMOPHORE
AB The development of photocaging groups activated by near-IR light would enable new approaches for basic research and allow for spatial and temporal control of drug delivery. Here we report a near-IR light-initiated uncaging reaction sequence based on readily synthesized C4'-dialkylamine-substituted heptamethine cyanines. Phenol-containing small molecules are uncaged through sequential release of the C4'-amine and intramolecular cyclization. The release sequence is initiated by a previously unexploited photochemical reaction of the cyanine fluorophore scaffold. The uncaging process is compatible with biological milieu and is initiated with low intensity 690 nm light. We show that cell viability can be inhibited through light-dependent release of the estrogen receptor antagonist, 4-hydroxycyclofen. In addition, through uncaging of the same compound, gene expression is controlled with near-IR light in a ligand-dependent CreER(T)/LoxP-reporter cell line derived from transgenic mice. These studies provide a chemical foundation that we expect will enable specific delivery of small molecules using cytocompatible, tissue penetrant near-IR light.
C1 [Gorka, Alexander P.; Nani, Roger R.; Schnermann, Martin J.] NCI, Chem Biol Lab, Frederick, MD 21702 USA.
[Zhu, Jianjian; Mackem, Susan] NCI, Canc & Dev Biol Lab, Ctr Canc Res, Frederick, MD 21702 USA.
RP Schnermann, MJ (reprint author), NCI, Chem Biol Lab, 376 Boyles St, 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 members of the Chemical Biology Laboratory for helpful comments
and suggestions. We thank Dr. Joseph Barchi for NMR assistance and Dr.
James Kelley for mass spectrometric analysis. We also gratefully
acknowledge Dr. Hisataka Kobayashi for advice and assistance with the
LED light source, Dr. Stephen Lockett, Ms. Kim Peifley, and the Optical
Microscopy and Analysis Laboratory (Advanced Technology Program,
Frederick National Laboratory for Cancer Research) for their invaluable
expertise and assistance in obtaining confocal fluorescence images, and
Ms. Kathleen Noer, Ms. Roberta Matthai, and the Frederick CCR Flow
Cytometry Core (Cancer and Inflammation Program, NCIFrederick) for help
with flow cytometry analysis. 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 49
TC 30
Z9 30
U1 10
U2 90
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 OCT 8
PY 2014
VL 136
IS 40
BP 14153
EP 14159
DI 10.1021/ja5065203
PG 7
WC Chemistry, Multidisciplinary
SC Chemistry
GA AQ7VG
UT WOS:000343026700034
PM 25211609
ER
PT J
AU Huang, P
Rong, PF
Jin, A
Yan, XF
Zhang, MG
Lin, J
Hu, H
Wang, Z
Yue, XY
Li, WW
Niu, G
Zeng, WB
Wang, W
Zhou, KC
Chen, XY
AF Huang, Peng
Rong, Pengfei
Jin, Albert
Yan, Xuefeng
Zhang, Molly Gu
Lin, Jing
Hu, Hao
Wang, Zhe
Yue, Xuyi
Li, Wanwan
Niu, Gang
Zeng, Wenbin
Wang, Wei
Zhou, Kechao
Chen, Xiaoyuan
TI Dye-Loaded Ferritin Nanocages for Multimodal Imaging and Photothermal
Therapy
SO ADVANCED MATERIALS
LA English
DT Article
DE theranostics; ferritin; fluorescence imaging; photoacoustic imaging;
photothermal therapy
ID PHOTODYNAMIC THERAPY; IN-VIVO; INDOCYANINE GREEN; DRUG-DELIVERY; GOLD
NANORODS; CANCER-CELLS; NANOPARTICLES; AGENT; PHOTOSENSITIZERS;
NANOCRYSTALS
C1 [Huang, Peng; Rong, Pengfei; Yan, Xuefeng; Zhang, Molly Gu; Lin, Jing; Hu, Hao; Wang, Zhe; Yue, Xuyi; Li, Wanwan; Niu, Gang; Chen, Xiaoyuan] NIBIB, Lab Mol Imaging & Nanomed LOMIN, NIH, Bethesda, MD 20892 USA.
[Rong, Pengfei; Zeng, Wenbin; Zhou, Kechao] Cent S Univ, State Key Lab Powder Met, Changsha 410083, Hunan, Peoples R China.
[Rong, Pengfei; Wang, Wei] Cent S Univ, Dept Radiol, Xiangya Hosp 3, Changsha 410013, Hunan, Peoples R China.
[Jin, Albert] NIBIB, Lab Cellular Imaging & Macromol Biophys, NIH, Bethesda, MD 20892 USA.
[Wang, Zhe; Yue, Xuyi] Xiamen Univ, Sch Publ Hlth, Ctr Mol Imaging & Translat Med, Xiamen 361005, Fujian, Peoples R China.
RP Huang, P (reprint author), NIBIB, Lab Mol Imaging & Nanomed LOMIN, NIH, Bethesda, MD 20892 USA.
EM peng.huang@nih.gov; shawn.chen@nih.gov
RI Huang, Peng/H-9985-2013; Huang, Peng/R-2480-2016;
OI Huang, Peng/0000-0003-3651-7813; Jin, Albert/0000-0003-3826-1081
FU National Key Basic Research Program (973 Project) [2010CB933901,
2013CB733802, 2014CB744503]; National Science Foundation of China
[81272987, 31170961, 51102258, 81371596]; Intramural Research Program
(IRP) of the NIBIB, NIH
FX This work was supported by the National Key Basic Research Program (973
Project) (2010CB933901, 2013CB733802, 2014CB744503), the National
Science Foundation of China (81272987, 31170961, 51102258, 81371596),
and the Intramural Research Program (IRP) of the NIBIB, NIH.
NR 40
TC 57
Z9 60
U1 35
U2 243
PU WILEY-V C H VERLAG GMBH
PI WEINHEIM
PA BOSCHSTRASSE 12, D-69469 WEINHEIM, GERMANY
SN 0935-9648
EI 1521-4095
J9 ADV MATER
JI Adv. Mater.
PD OCT 8
PY 2014
VL 26
IS 37
BP 6401
EP 6408
DI 10.1002/adma.201400914
PG 8
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 AQ5JH
UT WOS:000342843600004
PM 25123089
ER
PT J
AU Jones, RR
DellaValle, CT
Flory, AR
Nordan, A
Hoppin, JA
Hofmann, JN
Chen, HL
Giglierano, J
Lynch, CF
Freeman, LEB
Rushton, G
Ward, MH
AF Jones, Rena R.
DellaValle, Curt T.
Flory, Abigail R.
Nordan, Alex
Hoppin, Jane A.
Hofmann, Jonathan N.
Chen, Honglei
Giglierano, James
Lynch, Charles F.
Freeman, Laura E. Beane
Rushton, Gerard
Ward, Mary H.
TI Accuracy of residential geocoding in the Agricultural Health Study
SO INTERNATIONAL JOURNAL OF HEALTH GEOGRAPHICS
LA English
DT Article
DE Geocoding; Positional error; Rural location; Environmental exposure
assessment; Accuracy
ID POSITIONAL ACCURACY; ADDRESSES; EXPOSURE
AB Background: Environmental exposure assessments often require a study participant's residential location, but the positional accuracy of geocoding varies by method and the rural status of an address. We evaluated geocoding error in the Agricultural Health Study (AHS), a cohort of pesticide applicators and their spouses in Iowa and North Carolina, U.S.A.
Methods: For 5,064 AHS addresses in Iowa, we compared rooftop coordinates as a gold standard to two alternate locations: 1) E911 locations (intersection of the private and public road), and 2) geocodes generated by matching addresses to a commercial street database (NAVTEQ) or placed manually. Positional error (distance in meters (m) from the rooftop) was assessed overall and separately for addresses inside (non-rural) or outside town boundaries (rural). We estimated the sensitivity and specificity of proximity-based exposures (crops, animal feeding operations (AFOs)) and the attenuation in odds ratios (ORs) for a hypothetical nested case-control study. We also evaluated geocoding errors within two AHS subcohorts in Iowa and North Carolina by comparing them to GPS points taken at residences.
Results: Nearly two-thirds of the addresses represented rural locations. Compared to the rooftop gold standard, E911 locations were more accurate overall than address-matched geocodes (median error 39 and 90 m, respectively). Rural addresses generally had greater error than non-rural addresses, although errors were smaller for E911 locations. For highly prevalent crops within 500 m (>97% of homes), sensitivity was >95% using both data sources; however, lower specificities with address-matched geocodes (more common for rural addresses) led to substantial attenuation of ORs (e.g., corn <500 m ORobs = 1.47 vs. ORtrue = 2.0). Error in the address-matched geocodes resulted in even greater ORobs attenuation for AFO exposures. Errors for North Carolina addresses were generally smaller than those in Iowa.
Conclusions: Geocoding error can be minimized when known coordinates are available to test alternative data and methods. Our assessment suggests that where E911 locations are available, they offer an improvement upon address-matched geocodes for rural addresses. Exposure misclassification resulting from positional error is dependent on the geographic database, geocoding method, and the prevalence of exposure.
C1 [Jones, Rena R.; DellaValle, Curt T.; Nordan, Alex; Hofmann, Jonathan N.; Freeman, Laura E. Beane; Ward, Mary H.] NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Rockville, MD 20850 USA.
[Flory, Abigail R.] Westat Corp, Rockville, MD USA.
[Rushton, Gerard] Univ Iowa, Dept Geog & Sustainabil Sci, Iowa City, IA USA.
[Hoppin, Jane A.] N Carolina State Univ, Dept Biol Sci, Raleigh, NC 27695 USA.
[Chen, Honglei] NIEHS, Epidemiol Branch, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA.
[Giglierano, James] Iowa Geol & Water Survey, Iowa Dept Nat Resources, Iowa City, IA USA.
[Lynch, Charles F.] Univ Iowa, Coll Publ Hlth, Dept Epidemiol, Iowa City, IA USA.
RP Jones, RR (reprint author), NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, 9609 Med Ctr Dr, Rockville, MD 20850 USA.
EM rena.jones@nih.gov
RI Beane Freeman, Laura/C-4468-2015;
OI Beane Freeman, Laura/0000-0003-1294-4124; Chen,
Honglei/0000-0003-3446-7779
FU Intramural NIH HHS; NCI NIH HHS [P30 CA086862, Z01 CP010119]; NIEHS NIH
HHS [Z01 ES049030]
NR 22
TC 4
Z9 4
U1 1
U2 4
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1476-072X
J9 INT J HEALTH GEOGR
JI Int. J. Health Geogr.
PD OCT 7
PY 2014
VL 13
AR 37
DI 10.1186/1476-072X-13-37
PG 9
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA AU9RE
UT WOS:000345931700001
PM 25292160
ER
PT J
AU Lennox, JL
Landovitz, RJ
Ribaudo, HJ
Ofotokun, I
Na, LH
Godfrey, C
Kuritzkes, DR
Sagar, M
Brown, TT
Cohn, SE
McComsey, GA
Aweeka, F
Fichtenbaum, CJ
Presti, RM
Koletar, SL
Haas, DW
Patterson, KB
Benson, CA
Baugh, BP
Leavitt, RY
Rooney, JF
Seekins, D
Currier, JS
AF Lennox, Jeffrey L.
Landovitz, Raphael J.
Ribaudo, Heather J.
Ofotokun, Ighovwerha
Na, Lumine H.
Godfrey, Catherine
Kuritzkes, Daniel R.
Sagar, Manish
Brown, Todd T.
Cohn, Susan E.
McComsey, Grace A.
Aweeka, Francesca
Fichtenbaum, Carl J.
Presti, Rachel M.
Koletar, Susan L.
Haas, David W.
Patterson, Kristine B.
Benson, Constance A.
Baugh, Bryan P.
Leavitt, Randi Y.
Rooney, James F.
Seekins, Daniel
Currier, Judith S.
CA ACTG A5257 Team
TI Efficacy and Tolerability of 3 Nonnucleoside Reverse Transcriptase
Inhibitor-Sparing Antiretroviral Regimens for Treatment-Naive Volunteers
Infected With HIV-1
SO ANNALS OF INTERNAL MEDICINE
LA English
DT Article
ID DISOPROXIL FUMARATE; RITONAVIR; THERAPY; INDIVIDUALS; COBICISTAT; TRIAL;
RISK
AB Background: Nonnucleoside reverse transcriptase inhibitor-based antiretroviral therapy is not suitable for all treatment-naive HIV-infected persons.
Objective: To evaluate 3 nonnucleoside reverse transcriptase inhibitor-sparing initial antiretroviral regimens to show equivalence for virologic efficacy and tolerability.
Design: A phase 3, open-label study randomized in a 1: 1: 1 ratio with follow-up for at least 96 weeks. (ClinicalTrials.gov: NCT00811954)
Setting: 57 sites in the United States and Puerto Rico.
Patients: Treatment-naive persons aged 18 years or older with HIV-1 RNA levels greater than 1000 copies/mL without resistance to nucleoside reverse transcriptase inhibitors or protease inhibitors.
Intervention: Atazanavir, 300 mg/d, with ritonavir, 100 mg/d; raltegravir, 400 mg twice daily; or darunavir, 800 mg/d, with ritonavir, 100 mg/d, plus combination emtricitabine, 200 mg/d, and tenofovir disoproxil fumarate, 300 mg/d.
Measurements: Virologic failure, defined as a confirmed HIV-1 RNA level greater than 1000 copies/mL at or after 16 weeks and before 24 weeks or greater than 200 copies/mL at or after 24 weeks, and tolerability failure, defined as discontinuation of atazanavir, raltegravir, or darunavir for toxicity. A secondary end point was a combination of virologic efficacy and tolerability.
Results: Among 1809 participants, all pairwise comparisons of incidence of virologic failure over 96 weeks showed equivalence within a margin of equivalence defined as -10% to 10%. Raltegravir and ritonavir-boosted darunavir were equivalent for tolerability, whereas ritonavir-boosted atazanavir resulted in a 12.7% and 9.2% higher incidence of tolerability discontinuation than raltegravir and ritonavir-boosted darunavir, respectively, primarily because of hyperbilirubinemia. For combined virologic efficacy and tolerability, ritonavir-boosted darunavir was superior to ritonavir-boosted atazanavir, and raltegravir was superior to both protease inhibitors. Antiretroviral resistance at the time of virologic failure was rare but more frequent with raltegravir.
Limitation: The trial was open-label, and ritonavir was not provided.
Conclusion: Over 2 years, all 3 regimens attained high and equivalent rates of virologic control. Tolerability of regimens containing raltegravir or ritonavir-boosted darunavir was superior to that of the ritonavir-boosted atazanavir regimen.
C1 Grady Mem Hosp, Atlanta, GA USA.
[Lennox, Jeffrey L.] Emory Univ, Sch Med, Atlanta, GA 30303 USA.
Ctr Clin AIDS Res & Educ, Los Angeles, CA USA.
Univ Calif Los Angeles, Los Angeles, CA 90035 USA.
Harvard Univ, Sch Publ Hlth, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA.
Boston Univ, Sch Med, Boston, MA 02118 USA.
[Godfrey, Catherine] NIAID, NIH, Bethesda, MD 20892 USA.
Johns Hopkins Univ, Baltimore, MD 21287 USA.
[Cohn, Susan E.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA.
Case Western Reserve Univ, Cleveland, OH 44106 USA.
[Aweeka, Francesca] Univ Calif San Francisco, Sch Pharm, San Francisco, CA 94143 USA.
[Fichtenbaum, Carl J.] Univ Cincinnati, Coll Med, Cincinnati, OH 45267 USA.
[Presti, Rachel M.] Washington Univ, Sch Med, St Louis, MO 63110 USA.
Ohio State Univ, Coll Med, Columbus, OH 43210 USA.
Vanderbilt Univ, Sch Med, Nashville, TN 37212 USA.
Univ N Carolina, Sch Med, Chapel Hill, NC 27599 USA.
Univ Calif San Diego, Sch Med, San Diego, CA 92103 USA.
[Baugh, Bryan P.] Janssen Sci Affairs, Titusville, NJ 08560 USA.
Merck, Whitehouse Stn, NJ USA.
[Rooney, James F.] Gilead Sci, Foster City, CA 94404 USA.
Bristol Myers Squibb Co, New York, NY 10154 USA.
RP Lennox, JL (reprint author), Emory Univ, Sch Med, Div Infect Dis, 69 Jesse Hill Jr Dr SE,Suite 202, Atlanta, GA 30303 USA.
EM jlennox@emory.edu
RI Ofotokun, Ighovwerha/L-6545-2015
OI Ofotokun, Ighovwerha/0000-0003-2735-1903
FU National Institute of Allergy and Infectious Diseases
FX Primary Funding Source: National Institute of Allergy and Infectious
Diseases.
NR 21
TC 73
Z9 73
U1 0
U2 2
PU AMER COLL PHYSICIANS
PI PHILADELPHIA
PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA
SN 0003-4819
EI 1539-3704
J9 ANN INTERN MED
JI Ann. Intern. Med.
PD OCT 7
PY 2014
VL 161
IS 7
BP 461
EP +
DI 10.7326/M14-1084
PG 16
WC Medicine, General & Internal
SC General & Internal Medicine
GA AR9LU
UT WOS:000343896700004
PM 25285539
ER
PT J
AU Moon, HY
van Praag, H
AF Moon, Hyo Youl
van Praag, Henriette
TI Muscle Over Mind
SO CELL METABOLISM
LA English
DT Editorial Material
ID SKELETAL-MUSCLE; EXERCISE; AMPK; MICE
AB Depression is associated with elevated kynurenine levels, a tryptophan metabolite generated under stress and inflammatory conditions. Agudelo et al. (2014) now reveal how PGC-1a1 overexpression in muscle mimics anti-depressant effects of exercise by promoting kynurenine aminotransferase expression, likely preventing kynurenine from crossing the blood brain barrier to disrupt neural plasticity.
C1 [Moon, Hyo Youl; van Praag, Henriette] NIA, Neuroplast & Behav Unit, Neurosci Lab, NIH, Baltimore, MD 21224 USA.
RP van Praag, H (reprint author), NIA, Neuroplast & Behav Unit, Neurosci Lab, NIH, Baltimore, MD 21224 USA.
EM vanpraagh@mail.nih.gov
RI van Praag, Henriette/F-3939-2015
OI van Praag, Henriette/0000-0002-5727-434X
FU Intramural NIH HHS
NR 10
TC 7
Z9 7
U1 0
U2 19
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 OCT 7
PY 2014
VL 20
IS 4
BP 560
EP 562
DI 10.1016/j.cmet.2014.09.012
PG 3
WC Cell Biology; Endocrinology & Metabolism
SC Cell Biology; Endocrinology & Metabolism
GA AR4WI
UT WOS:000343586500005
PM 25295784
ER
PT J
AU Zhang, MG
March, ME
Lane, WS
Long, EO
AF Zhang, Minggang
March, Michael E.
Lane, William S.
Long, Eric O.
TI A signaling network stimulated by beta(2) integrin promotes the
polarization of lytic granules in cytotoxic cells
SO SCIENCE SIGNALING
LA English
DT Article
ID NATURAL-KILLER-CELLS; RESTING NK CELLS; IMMUNOLOGICAL SYNAPSE; LINKED
KINASE; FOCAL ADHESION; TARGET-CELLS; T-CELLS; RECEPTOR; PROTEIN; CDC42
AB Cytotoxic lymphocytes kill target cells through the polarized release of the contents of intracellular perforin-containing granules. In natural killer (NK) cells, the binding of beta(2) integrin to members of the intercellular adhesion molecule family is sufficient to promote not only the adhesion of NK cells to target cells but also the polarization of intracellular lytic granules toward the target. We used NK cells in an experimental system designed to enable us to study the polarization of lytic granules in the absence of their release through degranulation, as well as beta(2) integrin signaling independently of inside-out signals from other receptors. Through a proteomics approach, we identified a signaling network centered on an integrin-linked kinase (ILK)-Pyk2-paxillin core that was required for granule and microtubule-organizing center (MTOC) polarization. The conserved Cdc42-Par6 signaling pathway, which controls cell polarity, was also activated by ILK and was required for granule polarization toward the target cell. A subset of the signaling components required for polarization contributed also to the convergence of granules on the MTOC. These results delineate two connected signaling networks that are stimulated upon beta(2) integrin engagement and control the polarization of the MTOC and associated lytic granules toward the site of contact with target cells to mediate cellular cytotoxicity.
C1 [Zhang, Minggang; March, Michael E.; Long, Eric O.] NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA.
[Lane, William S.] Harvard Univ, FAS Ctr Syst Biol, Mass Spectrometry & Prote Resource Lab, Cambridge, MA 02138 USA.
RP Long, EO (reprint author), NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA.
EM eLong@nih.gov
RI Long, Eric/G-5475-2011;
OI Long, Eric/0000-0002-7793-3728; Zhang, Minggang/0000-0002-0945-5736
FU Intramural Research Program of the NIH, National Institute of Allergy
and Infectious Diseases
FX This work was supported by the Intramural Research Program of the NIH,
National Institute of Allergy and Infectious Diseases.
NR 58
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U1 1
U2 4
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 1945-0877
EI 1937-9145
J9 SCI SIGNAL
JI Sci. Signal.
PD OCT 7
PY 2014
VL 7
IS 346
AR ra96
DI 10.1126/scisignal.2005629
PG 13
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA AR1EH
UT WOS:000343325600005
PM 25292215
ER
PT J
AU Zerze, GH
Best, RB
Mittal, J
AF Zerze, Guel H.
Best, Robert B.
Mittal, Jeetain
TI Modest Influence of FRET Chromophores on the Properties of Unfolded
Proteins
SO BIOPHYSICAL JOURNAL
LA English
DT Article
ID SINGLE-MOLECULE FRET; COLD-SHOCK PROTEIN; RESONANCE ENERGY-TRANSFER;
SPECTROSCOPIC RULER; DENATURED STATE; FORCE-FIELD; SIMULATIONS;
COLLAPSE; DYNAMICS; TEMPERATURE
AB Single-molecule Forster resonance energy transfer (FRET) experiments are often used to study the properties of unfolded and intrinsically disordered proteins. Because of their large extinction coefficients and quantum yields, synthetic heteroaromatic chromophores covalently linked to the protein are often used as donor and acceptor fluorophores. A key issue in the interpretation of such experiments is the extent to which the properties of the unfolded chain may be affected by the presence of these chromophores. In this article, we investigate this question using all-atom explicit solvent replica exchange molecular dynamics simulations of three different unfolded or intrinsically disordered proteins. We find that the secondary structure and long-range contacts are largely the same in the presence or absence of the fluorophores, and that the dimensions of the chain with and without chromophores are similar. This suggests that, at least in the cases studied, extrinsic fluorophores have little effect on the structural properties of unfolded or disordered proteins. We also find that the critical FRET orientational factor kappa(2), has an average value and equilibrium distribution very close to that expected for isotropic orientations, which supports one of the assumptions frequently made when interpreting FRET efficiency in terms of distances.
C1 [Zerze, Guel H.; Mittal, Jeetain] Lehigh Univ, Dept Chem & Biomol Engn, Bethlehem, PA 18015 USA.
[Best, Robert B.] Natl Inst Diabet & Digest & Kidney Dis, Chem Phys Lab, NIH, Bethesda, MD USA.
RP Mittal, J (reprint author), Lehigh Univ, Dept Chem & Biomol Engn, Bethlehem, PA 18015 USA.
EM jeetain@lehigh.edu
RI Best, Robert/H-7588-2016
OI Best, Robert/0000-0002-7893-3543
FU National Science Foundation [CBET-1120399, TG-MCB-120014]; Intramural
Research Program of the National Institute of Diabetes and Digestive and
Kidney Diseases of the National Institutes of Health
FX This work was supported by National Science Foundation grant No.
CBET-1120399 (to J.M.). Use of the high-performance computing
capabilities of the Extreme Science and Engineering Discovery
Environment (XSEDE), which is supported by the National Science
Foundation grant no. TG-MCB-120014, is also gratefully acknowledged.
R.B.B was supported by the Intramural Research Program of the National
Institute of Diabetes and Digestive and Kidney Diseases of the National
Institutes of Health.
NR 48
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U1 3
U2 26
PU CELL PRESS
PI CAMBRIDGE
PA 50 HAMPSHIRE ST, FLOOR 5, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD OCT 7
PY 2014
VL 107
IS 7
BP 1654
EP 1660
DI 10.1016/j.bpj.2014.07.071
PG 7
WC Biophysics
SC Biophysics
GA AQ5XA
UT WOS:000342880700021
PM 25296318
ER
PT J
AU Sinner, MF
Tucker, NR
Lunetta, KL
Ozaki, K
Smith, JG
Trompet, S
Bis, JC
Lin, HH
Chung, MK
Nielsen, JB
Lubitz, SA
Krijthe, BP
Magnani, JW
Ye, JC
Gollob, MH
Tsunoda, T
Muller-Nurasyid, M
Lichtner, P
Peters, A
Dolmatova, E
Kubo, M
Smith, JD
Psaty, BM
Smith, NL
Jukema, W
Chasman, DI
Albert, CM
Ebana, Y
Furukawa, T
MacFarlane, PW
Harris, TB
Darbar, D
Dorr, M
Holst, AG
Svendsen, JH
Hofman, A
Uitterlinden, AG
Gudnason, V
Isobe, M
Malik, R
Dichgans, M
Rosand, J
Van Wagoner, DR
Benjamin, EJ
Milan, DJ
Melander, O
Heckbert, SR
Ford, I
Liu, YM
Barnard, J
Olesen, MS
Stricker, BHC
Tanaka, T
Kaeaeb, S
Ellinor, PT
AF Sinner, Moritz F.
Tucker, Nathan R.
Lunetta, Kathryn L.
Ozaki, Kouichi
Smith, J. Gustav
Trompet, Stella
Bis, Joshua C.
Lin, Honghuang
Chung, Mina K.
Nielsen, Jonas B.
Lubitz, Steven A.
Krijthe, Bouwe P.
Magnani, Jared W.
Ye, Jiangchuan
Gollob, Michael H.
Tsunoda, Tatsuhiko
Mueller-Nurasyid, Martina
Lichtner, Peter
Peters, Annette
Dolmatova, Elena
Kubo, Michiaki
Smith, Jonathan D.
Psaty, Bruce M.
Smith, Nicholas L.
Jukema, Wouter
Chasman, Daniel I.
Albert, Christine M.
Ebana, Yusuke
Furukawa, Tetsushi
MacFarlane, Peter W.
Harris, Tamara B.
Darbar, Dawood
Doerr, Marcus
Holst, Anders G.
Svendsen, Jesper H.
Hofman, Albert
Uitterlinden, Andre G.
Gudnason, Vilmundur
Isobe, Mitsuaki
Malik, Rainer
Dichgans, Martin
Rosand, Jonathan
Van Wagoner, David R.
Benjamin, Emelia J.
Milan, David J.
Melander, Olle
Heckbert, Susan R.
Ford, Ian
Liu, Yongmei
Barnard, John
Olesen, Morten S.
Stricker, Bruno H. C.
Tanaka, Toshihiro
Kaeaeb, Stefan
Ellinor, Patrick T.
CA METASTROKE Consortium AFGen Consor
TI Integrating Genetic, Transcriptional, and Functional Analyses to
Identify 5 Novel Genes for Atrial Fibrillation
SO CIRCULATION
LA English
DT Article
DE atrial fibrillation; epidemiology; genetics; gene expression;
polymorphism; single nucleotide; zebrafish
ID GENOME-WIDE ASSOCIATION; ISCHEMIC-STROKE; RISK-FACTORS; PR INTERVAL;
HEART-RATE; VARIANTS; ONSET; LOCI; METAANALYSIS; PRAVASTATIN
AB Background-Atrial fibrillation (AF) affects >30 million individuals worldwide and is associated with an increased risk of stroke, heart failure, and death. AF is highly heritable, yet the genetic basis for the arrhythmia remains incompletely understood.
Methods and Results-To identify new AF-related genes, we used a multifaceted approach, combining large-scale genotyping in 2 ethnically distinct populations, cis-eQTL (expression quantitative trait loci) mapping, and functional validation. Four novel loci were identified in individuals of European descent near the genes NEURL (rs12415501; relative risk [RR]=1.18; 95% confidence interval [CI], 1.13-1.23; P=6.5x10(-16)), GJA1 (rs13216675; RR=1.10; 95% CI, 1.06-1.14; P=2.2x10(-8)), TBX5 (rs10507248; RR=1.12; 95% CI, 1.08-1.16; P=5.7x10(-11)), and CAND2 (rs4642101; RR=1.10; 95% CI, 1.06-1.14; P=9.8x10(-9)). In Japanese, novel loci were identified near NEURL (rs6584555; RR=1.32; 95% CI, 1.26-1.39; P=2.0x10(-25)) and CUX2 (rs6490029; RR=1.12; 95% CI, 1.08-1.16; P=3.9x10(-9)). The top single-nucleotide polymorphisms or their proxies were identified as cis-eQTLs for the genes CAND2 (P=2.6x10(-19)), GJA1 (P=2.66x10(-6)), and TBX5 (P=1.36x10(-5)). Knockdown of the zebrafish orthologs of NEURL and CAND2 resulted in prolongation of the atrial action potential duration (17% and 45%, respectively).
Conclusions-We have identified 5 novel loci for AF. Our results expand the diversity of genetic pathways implicated in AF and provide novel molecular targets for future biological and pharmacological investigation.
C1 [Sinner, Moritz F.; Mueller-Nurasyid, Martina; Kaeaeb, Stefan] Univ Munich, Dept Med 1, Univ Hosp Munich, D-80336 Munich, Germany.
[Tucker, Nathan R.; Lubitz, Steven A.; Ye, Jiangchuan; Dolmatova, Elena; Milan, David J.; Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA.
[Lunetta, Kathryn L.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Lunetta, Kathryn L.; Lin, Honghuang; Benjamin, Emelia J.] NHLBI, Framingham, MA USA.
[Lunetta, Kathryn L.; Lin, Honghuang; Benjamin, Emelia J.] Boston Univ, Framingham Heart Study, Framingham, MA USA.
[Ozaki, Kouichi; Tanaka, Toshihiro] RIKEN Ctr Integrat Med Sci, Lab Cardiovasc Dis, Yokohama, Kanagawa, Japan.
[Smith, J. Gustav] Broad Inst Harvard & MIT, ProgramMed & Populat Genet, Cambridge, MA USA.
[Smith, J. Gustav] Lund Univ, Dept Cardiol, Lund, Sweden.
[Trompet, Stella; Jukema, Wouter] Leiden Univ, Dept Cardiol, Med Ctr, Leiden, Netherlands.
[Bis, Joshua C.; Psaty, Bruce M.; Smith, Nicholas L.; Heckbert, Susan R.] Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA.
[Bis, Joshua C.; Psaty, Bruce M.] Univ Washington, Dept Med, Seattle, WA USA.
[Lin, Honghuang] Boston Univ, Sch Med, Dept Med, Computat Biomed Sect, Boston, MA 02118 USA.
[Chung, Mina K.; Smith, Jonathan D.; Van Wagoner, David R.] Cleveland Clin, Dept Cardiovasc Med, Heart & Vasc Inst, Cleveland, OH 44106 USA.
[Chung, Mina K.; Van Wagoner, David R.] Cleveland Clin, Dept Mol Cardiol, Lerner Res Inst, Cleveland, OH 44106 USA.
[Nielsen, Jonas B.; Holst, Anders G.; Svendsen, Jesper H.; Olesen, Morten S.] Danish Natl Res Fdn, Ctr Cardiac Arrhythmia, Copenhagen, Denmark.
[Nielsen, Jonas B.; Holst, Anders G.; Svendsen, Jesper H.; Olesen, Morten S.] Univ Copenhagen, Rigshosp, Mol Cardiol Lab, Ctr Heart, DK-2100 Copenhagen, Denmark.
[Lubitz, Steven A.; Milan, David J.; Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA.
[Krijthe, Bouwe P.; Hofman, Albert; Uitterlinden, Andre G.; Stricker, Bruno H. C.] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.
[Krijthe, Bouwe P.; Hofman, Albert; Uitterlinden, Andre G.; Stricker, Bruno H. C.] NCHA, Rotterdam, Netherlands.
[Magnani, Jared W.; Benjamin, Emelia J.] Boston Univ, Sch Med, Dept Med, Cardiol Sect, Boston, MA 02118 USA.
[Gollob, Michael H.] Univ Ottawa, Inst Heart, Arrhythmia Res Lab, Ottawa, ON, Canada.
[Tsunoda, Tatsuhiko] RIKEN Ctr Integrat Med Sci, Lab Med Sci Math, Yokohama, Kanagawa, Japan.
[Mueller-Nurasyid, Martina] German Res Ctr Environm Hlth, Inst Genet Epidemiol, Helmholtz Zentrum Munchen, Neuherberg, Germany.
[Mueller-Nurasyid, Martina] Univ Munich, Inst Med Informat Biometry & Epidemiol, Munich, Germany.
[Lichtner, Peter] German Res Ctr Environm Hlth, Inst Human Genet, Helmholtz Zentrum Munchen, Neuherberg, Germany.
[Peters, Annette; Kaeaeb, Stefan] Deutsches Zentrum Herz Kreislaufforsch eV DZHK, Partner Site Munich Heart Alliance, Munich, Germany.
[Peters, Annette] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol 2, Neuherberg, Germany.
[Kubo, Michiaki] RIKEN Ctr Integrat Med Sci, Lab Genotyping Dev, Yokohama, Kanagawa, Japan.
[Smith, Jonathan D.] Cleveland Clin, Dept Cellular & Mol Med, Lerner Res Inst, Cleveland, OH 44106 USA.
[Psaty, Bruce M.; Smith, Nicholas L.; Heckbert, Susan R.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA USA.
[Psaty, Bruce M.; Smith, Nicholas L.; Heckbert, Susan R.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
[Psaty, Bruce M.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA.
[Smith, Nicholas L.] Dept Vet Affairs, Epidemiol Res & Informat Ctr, Off Res & Dev, Seattle, WA USA.
[Jukema, Wouter] Interuniv Cardiol Inst Netherlands, Utrecht, Netherlands.
[Chasman, Daniel I.; Albert, Christine M.] Harvard Univ, Sch Med, Boston, MA USA.
[Chasman, Daniel I.; Albert, Christine M.] Brigham & Womens Hosp, Div Prevent Med, Div Cardiovasc, Boston, MA 02115 USA.
[Ebana, Yusuke; Furukawa, Tetsushi] Tokyo Med & Dent Univ, Med Res Inst, Dept Bioinformat Pharmacol, Tokyo, Japan.
[MacFarlane, Peter W.] Univ Glasgow, Inst Cardiovasc & Med Sci, Glasgow G12 8QQ, Lanark, Scotland.
[Harris, Tamara B.] NIA, Lab Epidemiol Demog & Biometry, Intramural Res Program, NIH, Bethesda, MD 20892 USA.
[Darbar, Dawood] Vanderbilt Univ, Sch Med, Dept Med, Nashville, TN 37212 USA.
[Doerr, Marcus] Ernst Moritz Arndt Univ Greifswald, Dept Internal Med B, Greifswald, Germany.
[Svendsen, Jesper H.] Univ Copenhagen, Dept Clin Med, Fac Hlth Sci, Copenhagen, Denmark.
[Uitterlinden, Andre G.; Stricker, Bruno H. C.] Erasmus MC, Dept Internal Med, Rotterdam, Netherlands.
[Gudnason, Vilmundur] Iceland Heart Assoc, Res Inst, Kopavogur, Iceland.
[Gudnason, Vilmundur] Univ Iceland, Reykjavik, Iceland.
[Isobe, Mitsuaki] Tokyo Med & Dent Univ, Dept Cardiovasc Med, Tokyo, Japan.
[Malik, Rainer; Dichgans, Martin] Univ Munich, Inst Stroke & Dementia Res, Univ Hosp Munich, Munich, Germany.
[Dichgans, Martin] Munich Cluster Syst Neurol SyNergy, Munich, Germany.
[Rosand, Jonathan; Ellinor, Patrick T.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Rosand, Jonathan] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
[Rosand, Jonathan] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA USA.
[Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.
[Benjamin, Emelia J.] Boston Univ, Sch Med, Dept Med, Prevent Med Sect, Boston, MA 02118 USA.
[Melander, Olle] Lund Univ, Dept Clin Sci, Malmo, Sweden.
[Ford, Ian] Univ Glasgow, Robertson Ctr Biostat, Glasgow, Lanark, Scotland.
[Liu, Yongmei] Wake Forest Sch Med, Dept Epidemiol & Prevent, Winston Salem, NC USA.
[Barnard, John] Cleveland Clin, Dept Quantitat Hlth Sci, Lerner Res Inst, Cleveland, OH 44106 USA.
[Stricker, Bruno H. C.] Inspectorate Hlth Care, The Hague, Netherlands.
[Stricker, Bruno H. C.] Erasmus MC, Dept Med Informat, Rotterdam, Netherlands.
[Tanaka, Toshihiro] Tokyo Med & Dent Univ, Dept Human Genet & Dis Divers, Grad Sch Med & Dent Sci, Tokyo, Japan.
RP Kaeaeb, S (reprint author), Univ Munich, Dept Med 1, Univ Hosp Munich, Campus Innenstadt,Ziemssenstr 1, D-80336 Munich, Germany.
EM skaab@med.lmu.de
RI Krammel, Vera/N-4826-2014; Darbar, Dawood/C-9079-2015; Tsunoda,
Tatsuhiko/K-2061-2014; Gudnason, Vilmundur/K-6885-2015; Tanaka,
Toshihiro/J-9310-2014; Peters, Annette/A-6117-2011; Kubo,
Michiaki/N-7947-2015
OI Krammel, Vera/0000-0002-8273-8396; Darbar, Dawood/0000-0002-4103-5977;
Lin, Honghuang/0000-0003-3043-3942; Benjamin,
Emelia/0000-0003-4076-2336; Gudnason, Vilmundur/0000-0001-5696-0084;
Svendsen, Jesper Hastrup/0000-0001-8466-8515; Tanaka,
Toshihiro/0000-0001-6201-9784;
FU National Institutes of Health (NIH) [N01-AG-12100]; NIA Intramural
Research Program, Hjartavernd (the Icelandic Heart Association);
Althingi (the Icelandic Parliament); AFNET/KORA S4: German National
Genome Research Network [NGFN 01GS0838, 01GR0803, BMBF-01EZ0874, NGFN
01GI0204, 01GR0103, NGFN-2, NGFNPlus 01GS0823, NGFNPlus 01GS0834];
German Federal Ministry of Education and Research (BMBF) [01EZ0874];
German Competence Network on AF (AFNET) [01 GI 0204/N]; Leducq
Foundation [07-CVD 03]; BMBF Spitzen cluster personalized medicine m4
[01 EX1021E]; LMU Excellence Initiative [42595-6]; Munich Center of
Health Sciences (MC Health) as part of LMUinnovativ; BMBF; State of
Bavaria; German Heart Foundation; DZHK (German Center for Cardiovascular
Research); BMBF (German Ministry of Education and Research); ARIC:
National Heart, Lung, and Blood Institute (NHLBI) [N01-HC-55015,
N01-HC-55016, N01-HC-55018, N01-HC-55019, N01-HC-55020, N01-HC-55021,
N01-HC-55022, R01HL087641, R01HL59367, R01HL086694, U10HL054512];
National Human Genome Research Institute [U01HG004402]; NIH
[HHSN268200625226C, UL1RR025005, HHSN268200782096C, K23HL114724,
T32HL007208, R01HL092577, HL065962, R01HL104156, K24HL105780]; NIH
Roadmap for Medical Research; NHLBI [RC1-HL-099452, R01 HL090620, R01
HL111314, HHSN268201200036C, HHSN268200800007C, N01HC55222, N01HC85079,
N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086, HL080295,
HL087652, HL105756, N01-HC-25195, R01 HL 068986, R01 HL085251, R01
HL073410, HL 043851, HL69757]; American Heart Association. BioBank Japan
[09SDG2280087]; Ministry of Education, Culture, Sports, Science, and
Technology, Japan; SENSIN Medical Research Foundation, Japan; Danish
National Research Foundation Center for Cardiac Arrhythmia; John and
Birthe Meyer Foundation; Research Foundation of the Heart Center
Rigshospitalet; Laegernes Forsikringsforening af 1891; Arvid Nilsson
Foundation; Director Henrik Ibsens Foundation; Villadsen Family
Foundation; stockbroker Henry Hansen and wife Karla Hansen, born
Westergaard, Grant; Danish Heart Foundation
[07-10-R60-A1815-B573-22398]; NIH/National Center for Research Resources
Clinical and Translational Scienece Award [1UL-RR024989]; Heart and
Vascular Institute, Department of Cardiovascular Medicine, Cleveland
Clinic; Atrial Fibrillation Innovation Center, State of Ohio; National
Institute of Neurological Disorders and Stroke; National Institute on
Aging (NIA) [AG023629]; National Center for Advancing Translational
Sciences, Clinical & Translational Science Institute [UL1TR000124];
National Institute of Diabetes and Digestive and Kidney Disease Diabetes
Research Center [DK063491]; Affymetrix, Inc [N02-HL-6-4278]; Robert
Dawson Evans Endowment of the Department of Medicine at the Boston
University School of Medicine; Boston Medical Center; NIA [N01AG62101,
N01AG62103, N01AG62106, 1R01AG032098-01A1]; Intramural Research Program
of the NIH, NIA; Malmo city council; Swedish Heart-Lung foundation;
Thorsten Westerstrom Foundation; Swedish Medical Research Council;
Medical Faculty of Lund University; Malmo University Hospital; Albert
Pahlsson Research Foundation; Crafoord Foundation; Region Skane; Hulda
and Conrad Mossfelt Foundation; King Gustaf V and Queen Victoria Fund;
Lennart Hanssons Memorial Fund; Wallenberg Foundation; Doris Duke
Charitable Foundation Clinical Scientist Development Award [2014105];
American Heart Association Established Investigator Award
[13EIA14220013]; Heart and Stroke Foundations of Ontario; Canadian
Institutes for Health Research; government of Ontario; Heart and Stroke
Foundation of Ontario Clinician-Scientist Award; Bristol-Myers Squibb;
Netherlands Heart Foundation [2001 D 032]; Seventh Framework Program of
the European Commission [223004]; Netherlands Genomics Initiative
(Netherlands Consortium for Healthy Aging) [050-060-810]; Erasmus
Medical Center and Erasmus University Rotterdam; Netherlands
Organization for Scientific Research; Netherlands Organization for
Health Research and Development (ZonMw); Research Institute for Diseases
in the Elderly; Netherlands Heart Foundation; Ministry of Education,
Culture and Science; Ministry of Health Welfare and Sports; European
Commission; Municipality of Rotterdam; Netherlands Organization for
Scientific Research [175.010.2005.011, 911.03.012]; Netherlands Genomics
Initiative/Netherlands Organization for Scientific Research
[050-060-810]; Federal Ministry of Education and Research [01ZZ9603,
01ZZ0103, 01ZZ0403]; Ministry of Cultural Affairs; Social Ministry of
the Federal State of Mecklenburg-West Pomerania; research project
Greifswald Approach to Individualized Medicine; Ministry of Cultural
Affairs of the Federal State of Mecklenburg-West Pomerania [03IS2061A];
BMBF [03ZIK012]; Siemens Healthcare, Erlangen, Germany; Federal State of
Mecklenburg-West Pomerania; National Cancer Institute [CA 047988];
Donald W. Reynolds Foundation; Fondation Leducq; Amgen; Harris Family
Foundation [HL-093613]; Vascular Dementia Research Foundation; National
Institute of Neurological Disorders and Stroke [U01-NS069208]
FX This work was funded by the following: AGES: National Institutes of
Health (NIH) contract N01-AG-12100, NIA Intramural Research Program,
Hjartavernd (the Icelandic Heart Association), and the Althingi (the
Icelandic Parliament). AFNET/KORA S4: German National Genome Research
Network NGFN 01GS0838, 01GR0803, BMBF-01EZ0874, 01GR0803, NGFN 01GI0204,
01GR0103, NGFN-2, NGFNPlus 01GS0823, and NGFNPlus 01GS0834; German
Federal Ministry of Education and Research (BMBF) 01EZ0874; German
Competence Network on AF (AFNET) 01 GI 0204/N; Leducq Foundation 07-CVD
03, BMBF Spitzen cluster personalized medicine m4 (01 EX1021E), LMU
Excellence Initiative (42595-6); Munich Center of Health Sciences (MC
Health) as part of LMUinnovativ. The KORA platform is funded by the BMBF
and by the State of Bavaria. Dr Sinner was supported by the German Heart
Foundation. Dr Kaab was supported by the DZHK (German Center for
Cardiovascular Research) and BMBF (German Ministry of Education and
Research). ARIC: National Heart, Lung, and Blood Institute (NHLBI)
contracts N01-HC-55015, N01-HC-55016, N01-HC-55018, N01-HC-55019,
N01-HC-55020, N01-HC-55021, N01-HC-55022, R01HL087641, R01HL59367,
R01HL086694 and U10HL054512; National Human Genome Research Institute
contract U01HG004402; and NIH contract HHSN268200625226C. We thank the
staff and participants of the ARIC study for their important
contributions. Infrastructure was partly supported by grant UL1RR025005,
a component of the NIH and NIH Roadmap for Medical Research. Additional
support was provided by grants RC1-HL-099452 from the NHLBI and
09SDG2280087 from the American Heart Association. BioBank Japan: This
study was supported by the Ministry of Education, Culture, Sports,
Science, and Technology, Japan and by SENSIN Medical Research
Foundation, Japan. DANFIB: Danish National Research Foundation Center
for Cardiac Arrhythmia, the John and Birthe Meyer Foundation, the
Research Foundation of the Heart Center Rigshospitalet, Laegernes
Forsikringsforening af 1891, the Arvid Nilsson Foundation, and the
Director Henrik Ibsens Foundation, the Villadsen Family Foundation, the
stockbroker Henry Hansen and wife Karla Hansen, born Westergaard, Grant,
and the Danish Heart Foundation (grant 07-10-R60-A1815-B573-22398).
Cleveland Clinic: R01 HL090620 and R01 HL111314 from the NHLBI (Drs
Chung, Barnard, J. Smith, and Van Wagoner); NIH/National Center for
Research Resources Clinical and Translational Scienece Award
1UL-RR024989 (Drs Chung and Van Wagoner); Heart and Vascular Institute,
Department of Cardiovascular Medicine, Cleveland Clinic (Dr Chung);
Leducq Foundation 07-CVD 03 (Drs Van Wagoner and Chung); Atrial
Fibrillation Innovation Center, State of Ohio (Drs Van Wagoner and
Chung). CHS: NHLBI contracts HHSN268201200036C, HHSN268200800007C,
N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083,
and N01HC85086, and NHLBI grants HL080295, HL087652, and HL105756 with
additional contribution from the National Institute of Neurological
Disorders and Stroke. Additional support was provided through AG023629
from the National Institute on Aging (NIA). A full list of CHS
investigators and institutions can be found at http://www.CHS-NHLBI.org.
The provision of genotyping data was supported in part by the National
Center for Advancing Translational Sciences, Clinical & Translational
Science Institute grant UL1TR000124, and the National Institute of
Diabetes and Digestive and Kidney Disease Diabetes Research Center grant
DK063491 to the Southern California Diabetes Endocrinology Research
Center.; FHS: NHLBI and Boston University School of Medicine based on
analyses by Framingham Heart Study investigators participating in the
SNP Health Association Resource (SHARe) project. NHLBI's Framingham
Heart Study (contract No. N01-HC-25195) and its contract with
Affymetrix, Inc for genotyping services (contract No. N02-HL-6-4278). A
portion of this research used the Linux Cluster for Genetic Analysis
(LinGA-II) funded by the Robert Dawson Evans Endowment of the Department
of Medicine at the Boston University School of Medicine and Boston
Medical Center. Other support came from 1R01 HL092577 1RO1 HL076784,
1R01 AG028321, Evans Center for Interdisciplinary Biomedical Research
ARC on Atrial Fibrillation at Boston University (Benjamin), 6R01-NS
17950, and American Heart Association 09FTF2190028. Health ABC: NIA
contracts N01AG62101, N01AG62103, and N01AG62106. The genome-wide
association study was funded by NIA grant 1R01AG032098-01A1 to Wake
Forest University Health Sciences, and genotyping services were provided
by the Center for Inherited Disease Research (CIDR). CIDR is fully
funded through a federal contract from the NIH to The Johns Hopkins
University, contract No. HHSN268200782096C. This research was supported
in part by the Intramural Research Program of the NIH, NIA. HVH: NHLBI
R01 HL 068986, R01 HL085251, and R01 HL073410. MAC: The Malmo Diet and
Cancer study was made possible by grants from the Malmo city council. Dr
J.G. Smith was supported by the Swedish Heart-Lung foundation and the
Thorsten Westerstrom Foundation. Dr Melander was supported by the
Swedish Heart-Lung Foundation, the Swedish Medical Research Council, the
Medical Faculty of Lund University, the Malmo University Hospital, the
Albert Pahlsson Research Foundation, the Crafoord Foundation, the Region
Skane, the Hulda and Conrad Mossfelt Foundation, the King Gustaf V and
Queen Victoria Fund, the Lennart Hanssons Memorial Fund, and the
Wallenberg Foundation. MGH: Doris Duke Charitable Foundation Clinical
Scientist Development Award 2014105 (Dr Lubitz), NIH grants K23HL114724
(Dr Lubitz), T32HL007208 (Dr Tucker), R01HL092577 (Drs Ellinor and
Benjamin), HL065962, R01HL104156 and K24HL105780 (Dr Ellinor), and an
American Heart Association Established Investigator Award 13EIA14220013
(Ellinor). Ottawa: Heart and Stroke Foundations of Ontario (Dr Gollob),
and the Canadian Institutes for Health Research (Dr Gollob). Dr Gollob
is supported by the Early Researcher Award program from the government
of Ontario and from the Heart and Stroke Foundation of Ontario
Clinician-Scientist Award. PROSPER: Supported by an
investigator-initiated grant obtained from Bristol-Myers Squibb. Dr
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). RS-I / RS-II: RS-I is supported by the
Erasmus Medical Center and Erasmus University Rotterdam; the Netherlands
Organization for Scientific Research; The Netherlands Organization for
Health Research and Development (ZonMw); the Research Institute for
Diseases in the Elderly; The Netherlands Heart Foundation; the Ministry
of Education, Culture and Science; the Ministry of Health Welfare and
Sports; the European Commission; and the Municipality of Rotterdam.
Support for genotyping was provided by the Netherlands Organization for
Scientific Research (175.010.2005.011, 911.03.; 012) and Research
Institute for Diseases in the Elderly. This study was supported by the
Netherlands Genomics Initiative/Netherlands Organization for Scientific
Research project No. 050-060-810. SHIP: SHIP is part of the Community
Medicine Research Network of the University of Greifswald, Germany,
which is funded by the Federal Ministry of Education and Research
(grants 01ZZ9603, 01ZZ0103, and 01ZZ0403), the Ministry of Cultural
Affairs, and the Social Ministry of the Federal State of
Mecklenburg-West Pomerania. This work supported partly by the research
project Greifswald Approach to Individualized Medicine, which is funded
by the BMBF and the Ministry of Cultural Affairs of the Federal State of
Mecklenburg-West Pomerania (03IS2061A). Generation of genome-wide data
has been supported by the BMBF (grant 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. WGHS:
NHLBI HL 043851 (Buring) and HL69757 (Buring) and National Cancer
Institute CA 047988 (Buring), the Donald W. Reynolds Foundation and the
Fondation Leducq (Ridker), with collaborative scientific support and
funding for genotyping provided by Amgen. AF end-point confirmation was
supported by HL-093613 (Dr Albert) and a grant from the Harris Family
Foundation (Tedrow). METASTROKE: Dr Dichgans is supported by the
Vascular Dementia Research Foundation. Dr Rosand is supported by the
National Institute of Neurological Disorders and Stroke U01-NS069208.
None of the funding agencies had any role in the study design, data
collection or analysis, interpretation of the data, writing of the
manuscript, or the decision to submit the manuscript for publication.
NR 41
TC 42
Z9 42
U1 0
U2 19
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
EI 1524-4539
J9 CIRCULATION
JI Circulation
PD OCT 7
PY 2014
VL 130
IS 15
BP 1225
EP +
DI 10.1161/CIRCULATIONAHA.114.009892
PG 48
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA AQ8VH
UT WOS:000343113800009
PM 25124494
ER
PT J
AU Kassas, A
Moura, IC
Yamashita, Y
Scheffel, J
Guerin-Marchand, C
Blank, U
Sims, PJ
Wiedmer, T
Monteiro, RC
Rivera, J
Charles, N
Benhamou, M
AF Kassas, Asma
Moura, Ivan C.
Yamashita, Yumi
Scheffel, Jorg
Guerin-Marchand, Claudine
Blank, Ulrich
Sims, Peter J.
Wiedmer, Therese
Monteiro, Renato C.
Rivera, Juan
Charles, Nicolas
Benhamou, Marc
TI Regulation of the Tyrosine Phosphorylation of Phospholipid Scramblase 1
in Mast Cells That Are Stimulated through the High-Affinity IgE Receptor
SO PLOS ONE
LA English
DT Article
ID LEUKEMIA RBL-2H3 CELLS; GROWTH-FACTOR RECEPTOR; PLASMA-MEMBRANE;
FC-RECEPTORS; TRANSBILAYER MOVEMENT; MONOCLONAL-ANTIBODIES;
HISTAMINE-RELEASE; APOPTOTIC CELLS; GENE-EXPRESSION; PROTEIN
AB Engagement of high-affinity immunoglobulin E receptors (Fc epsilon RI) activates two signaling pathways in mast cells. The Lyn pathway leads to recruitment of Syk and to calcium mobilization whereas the Fyn pathway leads to phosphatidylinositol 3-kinase recruitment. Mapping the connections between both pathways remains an important task to be completed. We previously reported that Phospholipid Scramblase 1 (PLSCR1) is phosphorylated on tyrosine after cross-linking Fc epsilon RI on RBL-2H3 rat mast cells, amplifies mast cell degranulation, and is associated with both Lyn and Syk tyrosine kinases. Here, analysis of the pathway leading to PLSCR1 tyrosine phosphorylation reveals that it depends on the FcR gamma chain. Fc epsilon RI aggregation in Fyn-deficient mouse bone marrow-derived mast cells (BMMC) induced a more robust increase in Fc epsilon RI-dependent tyrosine phosphorylation of PLSCR1 compared to wild-type cells, whereas PLSCR1 phosphorylation was abolished in Lyn-deficient BMMC. Lyn association with PLSCR1 was not altered in Fyn-deficient BMMC. PLSCR1 phosphorylation was also dependent on the kinase Syk and significantly, but partially, dependent on detectable calcium mobilization. Thus, the Lyn/Syk/calcium axis promotes PLSCR1 phosphorylation in multiple ways. Conversely, the Fyn-dependent pathway negatively regulates it. This study reveals a complex regulation for PLSCR1 tyrosine phosphorylation in Fc epsilon RI-activated mast cells and that PLSCR1 sits at a crossroads between Lyn and Fyn pathways.
C1 [Kassas, Asma; Moura, Ivan C.; Guerin-Marchand, Claudine; Blank, Ulrich; Monteiro, Renato C.; Charles, Nicolas; Benhamou, Marc] Univ Paris 07, INSERM, U1149, Paris, France.
[Kassas, Asma; Moura, Ivan C.; Guerin-Marchand, Claudine; Blank, Ulrich; Monteiro, Renato C.; Charles, Nicolas; Benhamou, Marc] Univ Paris Diderot, Sorbonne Paris Cite, Lab Excellence INFLAMEX, DHU FIRE, Paris, France.
[Yamashita, Yumi; Scheffel, Jorg; Rivera, Juan] NIAMSD, Immunogenet Mol Lab, Mol Immunol & Inflammat Branch, NIH, Bethesda, MD 20892 USA.
[Sims, Peter J.; Wiedmer, Therese] Univ Rochester, Sch Med & Dent, Dept Med, Rochester, NY 14642 USA.
RP Charles, N (reprint author), Univ Paris 07, INSERM, U1149, Paris, France.
EM nicolas.charles@inserm.fr; marc.benhamou@inserm.fr
RI Charles, Nicolas/P-5430-2014;
OI Charles, Nicolas/0000-0002-5416-5834; Moura, Ivan/0000-0002-2977-0354;
Cruz Moura, Ivan/0000-0002-8418-2803
FU Fondation de France [2002004544]; Ligue Nationale Contre le Cancer;
Intramural Research Program, NIAMS, NIH; Investissements d'Avenir
programme [ANR-11-IDEX-0005-02]; Sorbonne Paris Cite; Laboratoire
d'excellence INFLAMEX
FX This work was supported in part by a grant from the Fondation de France
(2002004544). N.C. was supported in part by a grant from the Ligue
Nationale Contre le Cancer. The work of Y.Y., J.S. and J.R. was
supported by the Intramural Research Program, NIAMS, NIH. A.K. was
supported by Investissements d'Avenir programme ANR-11-IDEX-0005-02,
Sorbonne Paris Cite, Laboratoire d'excellence INFLAMEX. The funders had
no role in study design, data collection and analysis, decision to
publish, or preparation of the manuscript.
NR 53
TC 2
Z9 2
U1 1
U2 10
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD OCT 7
PY 2014
VL 9
IS 10
AR e109800
DI 10.1371/journal.pone.0109800
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AQ4VK
UT WOS:000342798000089
PM 25289695
ER
PT J
AU Wang, YM
Chakravarty, P
Ranes, M
Kelly, G
Brooks, PJ
Neilan, E
Stewart, A
Schiavo, G
Svejstrup, JQ
AF Wang, Yuming
Chakravarty, Probir
Ranes, Michael
Kelly, Gavin
Brooks, Philip J.
Neilan, Edward
Stewart, Aengus
Schiavo, Giampietro
Svejstrup, Jesper Q.
TI Dysregulation of gene expression as a cause of Cockayne syndrome
neurological disease
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE CSA; neurology; gene regulation; neuritogenesis; reprogramming
ID COUPLED DNA-REPAIR; XERODERMA-PIGMENTOSUM; HUMAN FIBROBLASTS;
UV-IRRADIATION; NEURONS; PROTEIN; CONVERSION; LIGHT; SENSITIVITY;
ELONGATION
AB Cockayne syndrome (CS) is a multisystem disorder with severe neurological symptoms. The majority of CS patients carry mutations in Cockayne syndrome group B (CSB), best known for its role in transcription-coupled nucleotide excision repair. Indeed, because various repair pathways are compromised in patient cells, CS is widely considered a genome instability syndrome. Here, we investigate the connection between the neuropathology of CS and dysregulation of gene expression. Transcriptome analysis of human fibroblasts revealed that even in the absence of DNA damage, CSB affects the expression of thousands of genes, many of which are neuronal genes. CSB is present in a significant subset of these genes, suggesting that regulation is direct, at the level of transcription. Importantly, reprogramming of CS fibroblasts to neuron-like cells is defective unless an exogenous CSB gene is introduced. Moreover, neuroblastoma cells from which CSB is depleted show defects in gene expression programs required for neuronal differentiation, and fail to differentiate and extend neurites. Likewise, neuron-like cells cannot bemaintained without CSB. Finally, a number of disease symptoms may be explained by marked gene expression changes in the brain of patients with CS. Together, these data point to dysregulation of gene regulatory networks as a cause of the neurological symptoms in CS.
C1 [Wang, Yuming; Ranes, Michael; Svejstrup, Jesper Q.] Canc Res UK London Res Inst, Mech Transcript Lab, S Mimms EN6 3LD, Herts, England.
[Chakravarty, Probir; Kelly, Gavin; Stewart, Aengus] Canc Res UK London Res Inst, Bioinformat & Biostat Grp, London WC2A 3LY, England.
[Brooks, Philip J.] Natl Ctr Adv Translat Sci, Natl Inst Alcohol Abuse & Alcoholism & Off Rare D, Lab Neurogenet, NIH, Bethesda, MD 20892 USA.
[Neilan, Edward] Harvard Univ, Sch Med, Boston Childrens Hosp, Boston, MA 02115 USA.
[Schiavo, Giampietro] UCL, Inst Neurol, Sobell Dept Motor Neurosci & Movement Disorders, London WC1N 3BG, England.
RP Svejstrup, JQ (reprint author), Canc Res UK London Res Inst, Mech Transcript Lab, S Mimms EN6 3LD, Herts, England.
EM jesper.svejstrup@cancer.org.uk
OI Svejstrup, Jesper/0000-0003-4964-6147
FU European Research Council; Cancer Research UK
FX Brain tissue samples were provided by the National Institute of Child
Health and Human Development Brain and Tissue Bank for Developmental
Disorders (University of Maryland, Baltimore). We thank Alan Lehman for
CS cell lines, Jean-Marc Egly for CSB antibody, and Wim Vermeulen for
Csb-/- mouse embryonic fibroblasts. We thank the Advanced
Sequencing Facility and the Cell Services Facility at the London
Research Institute for expert assistance, and members of the J.Q.S.
laboratory and numerous other colleagues for their comments on the
manuscript. This work was supported by grants from the European Research
Council and Cancer Research UK (to J.Q.S.). P.J.B. is also a Program
Officer in the Division of Metabolism and Health Effects, National
Institute on Alcohol Abuse and Alcoholism, National Institutes of
Health.
NR 37
TC 10
Z9 10
U1 1
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 OCT 7
PY 2014
VL 111
IS 40
BP 14454
EP 14459
DI 10.1073/pnas.1412569111
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AQ2QU
UT WOS:000342633900045
PM 25249633
ER
PT J
AU Vickers, KC
Landstreet, SR
Levin, MG
Shoucri, BM
Toth, CL
Taylor, RC
Palmisano, BT
Tabet, F
Cui, HL
Rye, KA
Sethupathy, P
Remaley, AT
AF Vickers, Kasey C.
Landstreet, Stuart R.
Levin, Michael G.
Shoucri, Bassem M.
Toth, Cynthia L.
Taylor, Robert C.
Palmisano, Brian T.
Tabet, Fatiha
Cui, Huanhuan L.
Rye, Kerry-Anne
Sethupathy, Praveen
Remaley, Alan T.
TI MicroRNA-223 coordinates cholesterol homeostasis
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE atherosclerosis; reverse cholesterol transport; posttranscriptional gene
regulation
ID HIGH-DENSITY-LIPOPROTEIN; CASSETTE TRANSPORTER A1; RECEPTOR SR-BI;
SCAVENGER RECEPTOR; HEPATOCELLULAR-CARCINOMA; CELL-PROLIFERATION;
KNOCKOUT MICE; EXPRESSION; IDENTIFICATION; PLASMA
AB MicroRNAs (miRNAs) regulate a wide variety of biological processes and contribute to metabolic homeostasis. Here, we demonstrate that microRNA-223 (miR-223), an miRNA previously associated with inflammation, also controls multiple mechanisms associated with cholesterol metabolism. miR-223 promoter activity and mature levels were found to be linked to cellular cholesterol states in hepatoma cells. Moreover, hypercholesterolemia was associated with increased hepatic miR-223 levels in athero-prone mice. miR-223 was found to regulate high-density lipoprotein-cholesterol (HDL-C) uptake, through direct targeting and repression of scavenger receptor BI, and to inhibit cholesterol biosynthesis through the direct repression of sterol enzymes 3-hydroxy-3-methylglutaryl-CoA synthase 1 and methylsterol monooxygenase 1 in humans. Additionally, miR-223 was found to indirectly promote ATP-binding cassette transporter A1 expression (mRNA and protein) through Sp3, thereby enhancing cellular cholesterol efflux. Finally, genetic ablation of miR-223 in mice resulted in increased HDL-C levels and particle size, as well as increased hepatic and plasma total cholesterol levels. In summary, we identified a critical role for miR-223 in systemic cholesterol regulation by coordinated posttranscriptional control of multiple genes in lipoprotein and cholesterol metabolism.
C1 [Vickers, Kasey C.; Levin, Michael G.; Shoucri, Bassem M.; Palmisano, Brian T.; Remaley, Alan T.] NHLBI, NIH, Bethesda, MD 20892 USA.
[Vickers, Kasey C.; Landstreet, Stuart R.; Toth, Cynthia L.; Taylor, Robert C.] Vanderbilt Univ, Sch Med, Dept Med, Nashville, TN 37232 USA.
[Tabet, Fatiha; Rye, Kerry-Anne] Heart Res Inst, Lipid Res Grp, Newtown, NSW 2042, Australia.
[Cui, Huanhuan L.] Baker IDI Heart & Diabet Inst, Melbourne, Vic 3004, Australia.
[Sethupathy, Praveen] Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA.
RP Vickers, KC (reprint author), NHLBI, NIH, Bethesda, MD 20892 USA.
EM kasey.c.vickers@Vanderbilt.edu
FU National Institutes of Health (NIH) NHLBI Intramural Research Program;
NIH [K22HL113039, DK20593, P01HL116263, 5R00DK09131803]; American Heart
Association [14CSA20660001]
FX We thank Fernando Camargo, Scott R. McKercher, Stuart Lipton, Michael P.
Anderson, Alonzo Jalan, Steve Demosky, John Stonik, Seth Thacker,
Maureen Sampson, the National Human Genome Research Institute Microarray
Core Facility (Abdel Elkahloun and Bhavesh Borate), and the National
Heart, Lung and Blood Institute (NHLBI) DNA Sequencing Core Facility
(Jun Zhu, PhD). This work was supported by the National Institutes of
Health (NIH) NHLBI Intramural Research Program. K.C.V. is supported by
NIH Grants K22HL113039, DK20593, and P01HL116263. K.C.V. and P.S. are
supported by American Heart Association Grant 14CSA20660001. P.S. is
supported by NIH Grant 5R00DK09131803.
NR 45
TC 53
Z9 55
U1 1
U2 18
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 OCT 7
PY 2014
VL 111
IS 40
BP 14518
EP 14523
DI 10.1073/pnas.1215767111
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AQ2QU
UT WOS:000342633900056
PM 25246565
ER
PT J
AU Mickenautsch, S
Fu, B
Gudehithlu, S
Berger, VW
AF Mickenautsch, Steffen
Fu, Bo
Gudehithlu, Sheila
Berger, Vance W.
TI Accuracy of the Berger-Exner test for detecting third-order selection
bias in randomised controlled trials: a simulation-based investigation
SO BMC MEDICAL RESEARCH METHODOLOGY
LA English
DT Article
DE Randomised trials; Selection bias; Berger-Exner test; Sensitivity;
Specificity; ROC curve
ID EMPIRICAL-EVIDENCE; QUALITY; INTERVENTION
AB Background: Randomised controlled trials (RCT) are highly influential upon medical decisions. Thus RCTs must not distort the truth. One threat to internal trial validity is the correct prediction of future allocations (selection bias). The Berger-Exner test detects such bias but has not been widely utilized in practice. One reason for this non-utilisation may be a lack of information regarding its test accuracy. The objective of this study is to assess the accuracy of the Berger-Exner test on the basis of relevant simulations for RCTs with dichotomous outcomes.
Methods: Simulated RCTs with various parameter settings were generated, using R software, and subjected to bias-free and selection bias scenarios. The effect size inflation due to bias was quantified. The test was applied in both scenarios and the pooled sensitivity and specificity, with 95% confidence intervals for alpha levels of 1%, 5%, and 20%, were computed. Summary ROC curves were generated and the relationships of parameters with test accuracy were explored.
Results: An effect size inflation of 71% - 99% was established. Test sensitivity was 1.00 (95% CI: 0.99 - 1.00) for alpha level 1%, 5%, and 20%; test specificity was 0.94 (95% CI: 0.93 - 0.96); 0.82 (95% CI: 0.80 - 0.84), and 0.56 (95% CI: 0.54 - 0.58) for alpha 1%, 5%, and 20%, respectively. Test accuracy was best with the maximal procedure used with a maximum tolerated imbalance (MTI) = 2 as the randomisation method at alpha 1%.
Conclusions: The results of this simulation study suggest that the Berger-Exner test is generally accurate for identifying third-order selection bias.
C1 [Mickenautsch, Steffen] Univ Witwatersrand, Fac Hlth Sci, SYST Initiat Dept Community Dent, ZA-2193 Johannesburg, South Africa.
[Fu, Bo] Univ Pittsburgh, GSPH, Dept Biostat, Pittsburgh, PA USA.
[Gudehithlu, Sheila; Berger, Vance W.] NCI, NIH, Rockville, MD USA.
[Gudehithlu, Sheila] Univ Illinois, Dept Stat, Champaign, IL USA.
RP Mickenautsch, S (reprint author), Univ Witwatersrand, Fac Hlth Sci, SYST Initiat Dept Community Dent, 7 York Rd, ZA-2193 Johannesburg, South Africa.
EM neem@global.co.za
RI FU, BO/J-4063-2015;
OI Mickenautsch, Steffen/0000-0002-4994-2328
NR 27
TC 5
Z9 5
U1 1
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 OCT 6
PY 2014
VL 14
AR 114
DI 10.1186/1471-2288-14-114
PG 11
WC Health Care Sciences & Services
SC Health Care Sciences & Services
GA AW7II
UT WOS:000346437400001
PM 25283963
ER
PT J
AU Ehrenberg, PK
Geretz, A
Baldwin, KM
Apps, R
Polonis, VR
Robb, ML
Kim, JH
Michael, NL
Thomas, R
AF Ehrenberg, Philip K.
Geretz, Aviva
Baldwin, Karen M.
Apps, Richard
Polonis, Victoria R.
Robb, Merlin L.
Kim, Jerome H.
Michael, Nelson L.
Thomas, Rasmi
TI High-throughput multiplex HLA genotyping by next-generation sequencing
using multi-locus individual tagging
SO BMC GENOMICS
LA English
DT Article
DE HLA; NGS; HLA typing; Illumina MiSeq
ID HIGH-RESOLUTION; IMMUNOLOGICAL SYNAPSE; CLASS-I; TRANSPLANTATION;
EXPRESSION; LOCI; POPULATION; MARROW; SYSTEM; LEVEL
AB Background: Unambiguous human leukocyte antigen (HLA) typing is important in transplant matching and disease association studies. High-resolution HLA typing that is not restricted to the peptide-binding region can decrease HLA allele ambiguities. Cost and technology constraints have hampered high-throughput and efficient high resolution unambiguous HLA typing. We have developed a method for HLA genotyping that preserves the very high-resolution that can be obtained by next-generation sequencing (NGS) but also achieves substantially increased efficiency. Unambiguous HLA-A, B, C and DRB1 genotypes can be determined for 96 individuals in a single run of the Illumina MiSeq.
Results: Long-range amplification of full-length HLA genes from four loci was performed in separate polymerase chain reactions (PCR) using primers and PCR conditions that were optimized to reduce co-amplification of other HLA loci. Amplicons from the four HLA loci of each individual were then pooled and subjected to enzymatic library generation. All four loci of an individual were then tagged with one unique index combination. This multi-locus individual tagging (MIT) method combined with NGS enabled the four loci of 96 individuals to be analyzed in a single 500 cycle sequencing paired-end run of the Illumina-MiSeq. The MIT-NGS method generated sequence reads from the four loci were then discriminated using commercially available NGS HLA typing software. Comparison of the MIT-NGS with Sanger sequence-based HLA typing methods showed that all the ambiguities and discordances between the two methods were due to the accuracy of the MIT-NGS method.
Conclusions: The MIT-NGS method enabled accurate, robust and cost effective simultaneous analyses of four HLA loci per sample and produced 6 or 8-digit high-resolution unambiguous phased HLA typing data from 96 individuals in a single NGS run.
C1 [Ehrenberg, Philip K.; Geretz, Aviva; Baldwin, Karen M.; Polonis, Victoria R.; Robb, Merlin L.; Kim, Jerome H.; Michael, Nelson L.; Thomas, Rasmi] US Mil HIV Res Program MHRP, Walter Reed Army Inst Res, Silver Spring, MD 20910 USA.
[Geretz, Aviva; Baldwin, Karen M.; Robb, Merlin L.; Thomas, Rasmi] Henry M Jackson Fdn Adv Mil Med, Bethesda, MD USA.
[Apps, Richard] LEIDOS Inc, Frederick Natl Lab Canc Res, Frederick, MD USA.
RP Thomas, R (reprint author), US Mil HIV Res Program MHRP, Walter Reed Army Inst Res, 503 Robert Grant Ave, Silver Spring, MD 20910 USA.
EM rthomas@hivresearch.org
FU Henry M. Jackson Foundation for the Advancement of Military Medicine,
Inc. [W81XWH-07-2-0067]; U.S. Department of Defense (DOD)
[W81XWH-07-2-0067]; U.S. National Institute of Allergy and Infectious
Disease
FX This work was supported by a cooperative agreement (W81XWH-07-2-0067)
between the Henry M. Jackson Foundation for the Advancement of Military
Medicine, Inc., and the U.S. Department of Defense (DOD). This research
was funded, in part, by the U.S. National Institute of Allergy and
Infectious Disease. The views expressed are those of the authors and
should not be construed to represent the positions of the U.S. Army or
the DOD. We would like to thank Dr. Yuko Yukhi from the National Cancer
Institute in Frederick for assistance with the HLA-DRB1 SBT protocol and
Sebastian Molnar, Mary Bryson and Kara Lombardi for PBMC separation. We
thank Tim Hague, Omixon for helpful comments.
NR 27
TC 14
Z9 15
U1 4
U2 15
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 OCT 6
PY 2014
VL 15
AR 864
DI 10.1186/1471-2164-15-864
PG 8
WC Biotechnology & Applied Microbiology; Genetics & Heredity
SC Biotechnology & Applied Microbiology; Genetics & Heredity
GA AQ9MT
UT WOS:000343179600003
PM 25283548
ER
PT J
AU Niu, L
Huang, WC
Umbach, DM
Li, LP
AF Niu, Liang
Huang, Weichun
Umbach, David M.
Li, Leping
TI IUTA: a tool for effectively detecting differential isoform usage from
RNA-Seq data
SO BMC GENOMICS
LA English
DT Article
DE Isoform usage; RNA-seq; Compositional data; Transcriptome profiling;
Tissue; R package
ID HIGH-DIMENSIONAL DATA; GENOME; QUANTIFICATION; TRANSCRIPTION;
EXPRESSION; GENE; MECHANISMS; DISEASE; MOUSE
AB Background: Most genes in mammals generate several transcript isoforms that differ in stability and translational efficiency through alternative splicing. Such alternative splicing can be tissue-and developmental stage-specific, and such specificity is sometimes associated with disease. Thus, detecting differential isoform usage for a gene between tissues or cell lines/types (differences in the fraction of total expression of a gene represented by the expression of each of its isoforms) is potentially important for cell and developmental biology.
Results: We present a new method IUTA that is designed to test each gene in the genome for differential isoform usage between two groups of samples. IUTA also estimates isoform usage for each gene in each sample as well as averaged across samples within each group. IUTA is the first method to formulate the testing problem as testing for equal means of two probability distributions under the Aitchison geometry, which is widely recognized as the most appropriate geometry for compositional data (vectors that contain the relative amount of each component comprising the whole). Evaluation using simulated data showed that IUTA was able to provide test results for many more genes than was Cuffdiff2 (version 2.2.0, released in Mar. 2014), and IUTA performed better than Cuffdiff2 for the limited number of genes that Cuffdiff2 did analyze. When applied to actual mouse RNA-Seq datasets from six tissues, IUTA identified 2,073 significant genes with clear patterns of differential isoform usage between a pair of tissues. IUTA is implemented as an R package and is available at http://www.niehs.nih.gov/research/resources/software/biostatistics/iuta/index.cfm.
Conclusions: Both simulation and real-data results suggest that IUTA accurately detects differential isoform usage. We believe that our analysis of RNA-seq data from six mouse tissues represents the first comprehensive characterization of isoform usage in these tissues. IUTA will be a valuable resource for those who study the roles of alternative transcripts in cell development and disease.
C1 [Niu, Liang; Huang, Weichun; Umbach, David M.; Li, Leping] NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA.
RP Li, LP (reprint author), NIEHS, Biostat Branch, POB 12233, Res Triangle Pk, NC 27709 USA.
EM li3@niehs.nih.gov
FU Intramural Research Program of the NIH, National Institute of
Environmental Health Sciences [ES101765]
FX This research was supported by Intramural Research Program of the NIH,
National Institute of Environmental Health Sciences (ES101765).
NR 46
TC 3
Z9 3
U1 1
U2 15
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 OCT 6
PY 2014
VL 15
AR 862
DI 10.1186/1471-2164-15-862
PG 13
WC Biotechnology & Applied Microbiology; Genetics & Heredity
SC Biotechnology & Applied Microbiology; Genetics & Heredity
GA AQ9MT
UT WOS:000343179600001
PM 25283306
ER
PT J
AU Polepally, PR
Huben, K
Vardy, E
Setola, V
Mosier, PD
Roth, BL
Zjawiony, JK
AF Polepally, Prabhakar R.
Huben, Krzysztof
Vardy, Eyal
Setola, Vincent
Mosier, Philip D.
Roth, Bryan L.
Zjawiony, Jordan K.
TI Michael acceptor approach to the design of new salvinorin A-based high
affinity ligands for the kappa-opioid receptor
SO EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
LA English
DT Article
DE Salvinorin A and B; Michael acceptor-type ligands; Kappa, delta and mu
opioid receptors; Molecular modeling
ID NEOCLERODANE DITERPENES; ANALOGS; MECHANISM; DISCOVERY; AGONIST
AB The neoclerodane diterpenoid salvinorin A is a major secondary metabolite isolated from the psychoactive plant Salvia divinorum. Salvinorin A has been shown to have high affinity and selectivity for the K-opioid receptor (KOR). To study the ligand-receptor interactions that occur between salvinorin A and the KOR, a new series of salvinorin A derivatives bearing potentially reactive Michael acceptor functional groups at C-2 was synthesized and used to probe the salvinorin A binding site. The K-, delta-, and mu-opioid receptor (KOR, DOR and MOR, respectively) binding affinities and KOR efficacies were measured for the new compounds. Although none showed wash-resistant irreversible binding, most of them showed high affinity for the KOR, and some exhibited dual affinity to KOR and MOR. Molecular modeling techniques based on the recently-determined crystal structure of the KOR combined with results from mutagenesis studies, competitive binding, functional assays and structure-activity relationships, and previous salvinorin A-KOR interaction models were used to identify putative interaction modes of the new compounds with the KOR and MOR. (C) 2014 Elsevier Masson SAS. All rights reserved.
C1 [Polepally, Prabhakar R.; Huben, Krzysztof; Zjawiony, Jordan K.] Univ Mississippi, Sch Pharm, Pharmaceut Sci Res Inst, Dept Biomol Sci,Div Pharmacognosy, University, MS 38677 USA.
[Vardy, Eyal; Setola, Vincent; Roth, Bryan L.] Univ N Carolina, Sch Med, NIMH Psychoact Drug Screening Program, Dept Pharmacol,Div Chem Biol & Med Chem, Chapel Hill, NC 27599 USA.
[Mosier, Philip D.] Virginia Commonwealth Univ, Dept Med Chem, Richmond, VA 23298 USA.
[Mosier, Philip D.] Virginia Commonwealth Univ, Inst Struct Biol & Drug Discovery, Richmond, VA 23298 USA.
[Huben, Krzysztof] Tech Univ Lodz, Inst Organ Chem, PL-90924 Lodz, Poland.
RP Zjawiony, JK (reprint author), Univ Mississippi, Sch Pharm, Pharmaceut Sci Res Inst, Dept Biomol Sci,Div Pharmacognosy, University, MS 38677 USA.
EM jordan@olemiss.edu
RI Roth, Bryan/F-3928-2010
FU NIH [R01 DA017204]; NIMH Psychoactive Drug Screening Program (PDSP)
[HHSN-271-2013-00017-C]; University of North Carolina Chapel Hill [NC
27599]
FX This work was supported by the NIH Grant R01 DA017204 and the NIMH
Psychoactive Drug Screening Program (PDSP-Contract number:
HHSN-271-2013-00017-C), University of North Carolina Chapel Hill, NC
27599 (BLR). The authors wish to thank Dr. Daneel Ferreira for thorough
review and editing the manuscript. The authors are also thankful to Dr.
Bin Wang and Dr. Avula Bharathi for their assistance with HRESIMS.
Finally, we would also like to thank Dr. Richard Westkaemper for many
useful discussions.
NR 30
TC 7
Z9 7
U1 2
U2 7
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 OCT 6
PY 2014
VL 85
BP 818
EP 829
DI 10.1016/j.ejmech.2014.07.077
PG 12
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA AQ5OY
UT WOS:000342859700068
PM 25193297
ER
PT J
AU Gupta, N
Stopfer, M
AF Gupta, Nitin
Stopfer, Mark
TI A Temporal Channel for Information in Sparse Sensory Coding
SO CURRENT BIOLOGY
LA English
DT Article
ID DROSOPHILA OLFACTORY MEMORY; PRIMARY VISUAL-CORTEX; MUSHROOM BODIES;
CORTICAL-NEURONS; SCHISTOCERCA-GREGARIA; ODOR REPRESENTATIONS; DESERT
LOCUST; KENYON CELLS; OSCILLATIONS; SYSTEM
AB Background: Sparse codes are found in nearly every sensory system, but the role of spike timing in sparse sensory coding is unclear. Here, we use the olfactory system of awake locusts to test whether the timing of spikes in Kenyon cells, a population of neurons that responds sparsely to odors, carries sensory information to and influences the responses of follower neurons.
Results: We characterized two major classes of direct followers of Kenyon cells. With paired intracellular and field potential recordings made during odor presentations, we found that these followers contain information about odor identity in the temporal patterns of their spikes rather than in the spike rate, the spike phase, or the identities of the responsive neurons. Subtly manipulating the relative timing of Kenyon cell spikes with temporally and spatially structured microstimulation reliably altered the response patterns of the followers.
Conclusions: Our results show that even remarkably sparse spiking responses can provide information through stimulus-specific variations in timing on the order of tens to hundreds of milliseconds and that these variations can determine the responses of downstream neurons. These results establish the importance of spike timing in a sparse sensory code.
C1 [Gupta, Nitin; Stopfer, Mark] NICHHD, NIH, Bethesda, MD 20892 USA.
RP Gupta, N (reprint author), Indian Inst Technol, Dept Biol Sci & Bioengn, Kanpur 208016, Uttar Pradesh, India.
EM guptan@iitk.ac.in; stopferm@mail.nih.gov
OI Gupta, Nitin/0000-0002-8408-3848
FU NIH-NICHD
FX We thank members of the M. S. laboratory and Maxim Bazhenov for helpful
discussions; George Dold and Bruce Pritchard for help with the current
stimulation setup; and Kui Sun for her excellent animal care. Microscopy
was performed at the Microscopy and Imaging Core (NICHD) with the kind
assistance of Vincent Schram. This work was supported by an intramural
grant from the NIH-NICHD to M.S.
NR 48
TC 6
Z9 6
U1 1
U2 16
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0960-9822
EI 1879-0445
J9 CURR BIOL
JI Curr. Biol.
PD OCT 6
PY 2014
VL 24
IS 19
BP 2247
EP 2256
DI 10.1016/j.cub.2014.08.021
PG 10
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA AQ4FB
UT WOS:000342747600019
PM 25264257
ER
PT J
AU Perkins, TA
Garcia, AJ
Paz-Soldan, VA
Stoddard, ST
Reiner, RC
Vazquez-Prokopec, G
Bisanzio, D
Morrison, AC
Halsey, ES
Kochel, TJ
Smith, DL
Kitron, U
Scott, TW
Tatem, AJ
AF Perkins, T. Alex
Garcia, Andres J.
Paz-Soldan, Valerie A.
Stoddard, Steven T.
Reiner, Robert C., Jr.
Vazquez-Prokopec, Gonzalo
Bisanzio, Donal
Morrison, Amy C.
Halsey, Eric S.
Kochel, Tadeusz J.
Smith, David L.
Kitron, Uriel
Scott, Thomas W.
Tatem, Andrew J.
TI Theory and data for simulating fine-scale human movement in an urban
environment
SO JOURNAL OF THE ROYAL SOCIETY INTERFACE
LA English
DT Article
DE activity space; agent-based model; co-location and contact networks;
human mobility; simulation; synthetic population
ID DENGUE VIRUS TRANSMISSION; HUMAN MOBILITY; INDIVIDUAL BEHAVIOR;
AEDES-AEGYPTI; IQUITOS; PERU; PATTERNS; EPIDEMIOLOGY; INFLUENZA;
NETWORKS
AB Individual-based models of infectious disease transmission depend on accurate quantification of fine-scale patterns of human movement. Existing models of movement either pertain to overly coarse scales, simulate some aspects of movement but not others, or were designed specifically for populations in developed countries. Here, we propose a generalizable framework for simulating the locations that an individual visits, time allocation across those locations, and population-level variation therein. As a case study, we fit alternative models for each of five aspects of movement (number, distance from home and types of locations visited; frequency and duration of visits) to interview data from 157 residents of the city of Iquitos, Peru. Comparison of alternative models showed that location type and distance from home were significant determinants of the locations that individuals visited and how much time they spent there. We also found that for most locations, residents of two neighbourhoods displayed indistinguishable preferences for visiting locations at various distances, despite differing distributions of locations around those neighbourhoods. Finally, simulated patterns of time allocation matched the interview data in a number of ways, suggesting that our framework constitutes a sound basis for simulating fine-scale movement and for investigating factors that influence it.
C1 [Perkins, T. Alex; Reiner, Robert C., Jr.; Smith, David L.; Kitron, Uriel; Scott, Thomas W.; Tatem, Andrew J.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Perkins, T. Alex; Stoddard, Steven T.; Reiner, Robert C., Jr.; Morrison, Amy C.; Scott, Thomas W.] Univ Calif Davis, Dept Entomol & Nematol, Davis, CA 95616 USA.
[Garcia, Andres J.] Univ Florida, Emerging Pathogens Inst, Gainesville, FL USA.
[Garcia, Andres J.] Univ Florida, Dept Geog, Gainesville, FL 32611 USA.
[Paz-Soldan, Valerie A.] Tulane Univ, Sch Publ Hlth & Trop Med, Dept Global Hlth Syst & Dev, New Orleans, LA 70118 USA.
[Vazquez-Prokopec, Gonzalo; Bisanzio, Donal; Kitron, Uriel] Emory Univ, Dept Environm Sci, Atlanta, GA 30322 USA.
[Halsey, Eric S.; Kochel, Tadeusz J.] US Naval Med Res Unit 6, Lima, Peru.
[Smith, David L.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
[Smith, David L.] Johns Hopkins Bloomberg Sch Publ Hlth, Malaria Res Inst, Baltimore, MD USA.
[Tatem, Andrew J.] Univ Southampton, Dept Geog & Environm, Southampton, Hants, England.
[Tatem, Andrew J.] Flowminder Fdn, Stockholm, Sweden.
RP Perkins, TA (reprint author), Univ Notre Dame, Dept Biol Sci, Notre Dame, IN 46556 USA.
EM taperkins@nd.edu
RI Smith, David/L-8850-2013;
OI Smith, David/0000-0003-4367-3849; Perkins, Alex/0000-0002-7518-4014
FU US National Institutes of Health-National Institute of Allergy and
Infectious Diseases (NIH/NIAID) [R01 AI069341-01]; Research and Policy
for Infectious Disease Dynamics (RAPIDD) programme of the Science and
Technology Directory, Department of Homeland Security, and Fogarty
International Center, National Institutes of Health; National Science
Foundation [0801544]; Quantitative Spatial Ecology, Evolution and
Environment Program at the University of Florida; NIH/NIAID
[U19AI089674]; Bill and Melinda Gates Foundation [OPP1106427, 1032350]
FX This research was funded by a grant from the US National Institutes of
Health-National Institute of Allergy and Infectious Diseases (NIH/NIAID)
award no. R01 AI069341-01 (to T. W. S.) and by the Research and Policy
for Infectious Disease Dynamics (RAPIDD) programme of the Science and
Technology Directory, Department of Homeland Security, and Fogarty
International Center, National Institutes of Health. A.J.G. was
partially supported by the National Science Foundation under grant no.
0801544 in the Quantitative Spatial Ecology, Evolution and Environment
Program at the University of Florida. A.J.T. was supported by grants
from NIH/NIAID (U19AI089674) and the Bill and Melinda Gates Foundation
(OPP1106427 and no. 1032350). This paper forms part of the outputs of
the WorldPop Project (www.worldpop.org.uk) and Flowminder
(www.flowminder.org). Authors E. S. H. and T.J.K. were US military
service members. This work was prepared as part of their official
duties. Title 17 U. S. C. 105 provides that 'Copyright protection under
this title is not available for any work of the United States
Government'. Title 17 U. S. C. 101 defines a US Government work as a
work prepared by military service members or employees of the US
Government as part of those persons' official duties. Disclaimer: the
views expressed in this article are those of the authors and do not
necessarily reflect the official policy or position of the Department of
the Navy, Department of Defense nor the US Government.
NR 61
TC 10
Z9 10
U1 1
U2 28
PU ROYAL SOC
PI LONDON
PA 6-9 CARLTON HOUSE TERRACE, LONDON SW1Y 5AG, ENGLAND
SN 1742-5689
EI 1742-5662
J9 J R SOC INTERFACE
JI J. R. Soc. Interface
PD OCT 6
PY 2014
VL 11
IS 99
AR 20140642
DI 10.1098/rsif.2014.0642
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AO1UP
UT WOS:000341100800032
ER
PT J
AU Dasari, S
Tchounwou, PB
AF Dasari, Shaloam
Tchounwou, Paul Bernard
TI Cisplatin in cancer therapy: Molecular mechanisms of action
SO EUROPEAN JOURNAL OF PHARMACOLOGY
LA English
DT Review
DE Cisplatin; Platinum-based drugs; Mechanisms of action; Cancer treatment
ID CELL LUNG-CANCER; PROTEIN-KINASE-C; PHASE-II-TRIAL; SIGNAL-REGULATED
KINASE; ANTICANCER DRUG CISPLATIN; METASTATIC BREAST-CANCER;
OVARIAN-CARCINOMA CELLS; COPPER TRANSPORTER CTR1; HEAT-SHOCK-PROTEIN;
COMBINATION CHEMOTHERAPY
AB Cisplatin, cisplatinum, or cis-diamminedichloroplatinum (II), is a well-known chemotherapeutic drug. It has been used for treatment of numerous human cancers including bladder, head and neck, lung, ovarian, and testicular cancers. It is effective against various types of cancers, including carcinomas, germ cell tumors, lymphomas, and sarcomas. Its mode of action has been linked to its ability to crosslink with the purine bases on the DNA; interfering with DNA repair mechanisms, causing DNA damage, and subsequently inducing apoptosis in cancer cells. However, because of drug resistance and numerous undesirable side effects such as severe kidney problems, allergic reactions, decrease immunity to infections, gastrointestinal disorders, hemorrhage, and hearing loss especially in younger patients, other platinum-containing anti-cancer drugs such as carboplatin, oxaliplatin and others, have also been used. Furthermore, combination therapies of cisplatin with other drugs have been highly considered to overcome drug-resistance and reduce toxicity. This comprehensive review highlights the physicochemical properties of cisplatin and related platinum-based drugs, and discusses its uses (either alone or in combination with other drugs) for the treatment of various human cancers. A special attention is paid to its molecular mechanisms of action, and its undesirable side effects. (C) 2014 Elsevier B.V. All rights reserved.
C1 [Dasari, Shaloam; Tchounwou, Paul Bernard] Jackson State Univ, Cell & Toxicogen Res Lab, NIH NIMHD RCMI Ctr Environm Hlth, Coll Sci Engn & Technol, Jackson, MS 39217 USA.
RP Tchounwou, PB (reprint author), Jackson State Univ, Cell & Toxicogen Res Lab, NIH NIMHD RCMI Ctr Environm Hlth, Coll Sci Engn & Technol, 1400 Lynch St,Box 18750, Jackson, MS 39217 USA.
EM paul.b.tchounwou@jsums.edu
FU National Institutes of Health through the RCMI Center for Environmental
Health at Jackson State University [G12MD007581]
FX The research described in this publication was made possible by a grant
from the National Institutes of Health (Grant no. G12MD007581) through
the RCMI Center for Environmental Health at Jackson State University.
NR 185
TC 224
Z9 235
U1 75
U2 342
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0014-2999
EI 1879-0712
J9 EUR J PHARMACOL
JI Eur. J. Pharmacol.
PD OCT 5
PY 2014
VL 740
BP 364
EP 378
DI 10.1016/j.ejphar.2014.07.025
PG 15
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA AO2OH
UT WOS:000341163700045
PM 25058905
ER
PT J
AU Vertes, PE
Alexander-Bloch, A
Bullmore, ET
AF Vertes, Petra E.
Alexander-Bloch, Aaron
Bullmore, Edward T.
TI Generative models of rich clubs in Hebbian neuronal networks and
large-scale human brain networks
SO PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES
LA English
DT Article
DE brain networks; generative model; rich club; neural network
ID SMALL-WORLD NETWORKS; COMMUNITY STRUCTURE; FUNCTIONAL NETWORKS; COMPLEX
NETWORKS; NERVOUS-SYSTEM; ORGANIZATION; COMMUNICATION; CONNECTOME;
PLASTICITY; TOPOLOGY
AB Rich clubs arise when nodes that are 'rich' in connections also forman elite, densely connected 'club'. In brain networks, rich clubs incur high physical connection costs but also appear to be especially valuable to brain function. However, little is known about the selection pressures that drive their formation. Here, we take two complementary approaches to this question: firstly we show, using generative modelling, that the emergence of rich clubs in large-scale human brain networks can be driven by an economic trade-off between connection costs and a second, competing topological term. Secondly we show, using simulated neural networks, that Hebbian learning rules also drive the emergence of rich clubs at the microscopic level, and that the prominence of these features increases with learning time. These results suggest that Hebbian learning may provide a neuronal mechanism for the selection of complex features such as rich clubs. The neural networks that we investigate are explicitly Hebbian, and we argue that the topological term in our model of large-scale brain connectivity may represent an analogous connection rule. This putative link between learning and rich clubs is also consistent with predictions that integrative aspects of brain network organization are especially important for adaptive behaviour.
C1 [Vertes, Petra E.; Alexander-Bloch, Aaron; Bullmore, Edward T.] Univ Cambridge, Dept Psychiat, Behav & Clin Neurosci Inst, Cambridge, England.
[Alexander-Bloch, Aaron] NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA.
[Alexander-Bloch, Aaron] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA.
[Bullmore, Edward T.] Cambridgeshire & Peterborough NHS Fdn Trust, Cambridge, England.
[Bullmore, Edward T.] GlaxoSmithKline, Immuno Psychiat, Alternat Discovery & Dev, Stevenage, Herts, England.
RP Vertes, PE (reprint author), Univ Cambridge, Dept Psychiat, Behav & Clin Neurosci Inst, Cambridge, England.
EM pv226@cam.ac.uk
OI Alexander-Bloch, Aaron/0000-0001-6554-1893; Vertes, Petra
E./0000-0002-0992-3210; Bullmore, Edward/0000-0002-8955-8283
FU Medical Research Council [MR/K020706/1]; Wellcome Trust
FX The Behavioural and Clinical Neuroscience Institute is supported by the
Medical Research Council and the Wellcome Trust. P.E.V. is supported by
the Medical Research Council (grant no. MR/K020706/1).
NR 45
TC 12
Z9 12
U1 1
U2 5
PU ROYAL SOC
PI LONDON
PA 6-9 CARLTON HOUSE TERRACE, LONDON SW1Y 5AG, ENGLAND
SN 0962-8436
EI 1471-2970
J9 PHILOS T R SOC B
JI Philos. Trans. R. Soc. B-Biol. Sci.
PD OCT 5
PY 2014
VL 369
IS 1653
SU SI
AR 20130531
DI 10.1098/rstb.2013.0531
PG 10
WC Biology
SC Life Sciences & Biomedicine - Other Topics
GA AO9RW
UT WOS:000341695200010
ER
PT J
AU Maxwell, EK
Schnitzler, CE
Havlak, P
Putnam, NH
Nguyen, AD
Moreland, RT
Baxevanis, AD
AF Maxwell, Evan K.
Schnitzler, Christine E.
Havlak, Paul
Putnam, Nicholas H.
Anh-Dao Nguyen
Moreland, R. Travis
Baxevanis, Andreas D.
TI Evolutionary profiling reveals the heterogeneous origins of classes of
human disease genes: implications for modeling disease genetics in
animals
SO BMC EVOLUTIONARY BIOLOGY
LA English
DT Article
DE Model organism selection; Human disease genes; Evolutionary genetics;
Comparative genomics
ID TRANSLATIONAL RESEARCH; A-I; GENOME; ZEBRAFISH; ORGANISM; MICE;
MULTICELLULARITY; INVERTEBRATES; DUPLICATION; EMERGENCE
AB Background: The recent expansion of whole-genome sequence data available from diverse animal lineages provides an opportunity to investigate the evolutionary origins of specific classes of human disease genes. Previous studies have observed that human disease genes are of particularly ancient origin. While this suggests that many animal species have the potential to serve as feasible models for research on genes responsible for human disease, it is unclear whether this pattern has meaningful implications and whether it prevails for every class of human disease.
Results: We used a comparative genomics approach encompassing a broad phylogenetic range of animals with sequenced genomes to determine the evolutionary patterns exhibited by human genes associated with different classes of disease. Our results support previous claims that most human disease genes are of ancient origin but, more importantly, we also demonstrate that several specific disease classes have a significantly large proportion of genes that emerged relatively recently within the metazoans and/or vertebrates. An independent assessment of the synonymous to non-synonymous substitution rates of human disease genes found in mammals reveals that disease classes that arose more recently also display unexpected rates of purifying selection between their mammalian and human counterparts.
Conclusions: Our results reveal the heterogeneity underlying the evolutionary origins of (and selective pressures on) different classes of human disease genes. For example, some disease gene classes appear to be of uncommonly recent (i.e., vertebrate-specific) origin and, as a whole, have been evolving at a faster rate within mammals than the majority of disease classes having more ancient origins. The novel patterns that we have identified may provide new insight into cases where studies using traditional animal models were unable to produce results that translated to humans. Conversely, we note that the larger set of disease classes do have ancient origins, suggesting that many non-traditional animal models have the potential to be useful for studying many human disease genes. Taken together, these findings emphasize why model organism selection should be done on a disease-by-disease basis, with evolutionary profiles in mind.
C1 [Maxwell, Evan K.; Schnitzler, Christine E.; Anh-Dao Nguyen; Moreland, R. Travis; Baxevanis, Andreas D.] NIH, Computat & Stat Genom Branch, Div Intramural Res, Bethesda, MD 20892 USA.
[Maxwell, Evan K.] Boston Univ, Bioinformat Program, Boston, MA 02215 USA.
[Havlak, Paul; Putnam, Nicholas H.] Rice Univ, Dept Ecol & Evolutionary Biol, Houston, TX 77005 USA.
[Havlak, Paul] Texas A&M Hlth Sci Ctr, Coll Med, Biomed Informat Core, Houston, TX 77030 USA.
RP Baxevanis, AD (reprint author), NIH, Computat & Stat Genom Branch, Div Intramural Res, Bldg 10, Bethesda, MD 20892 USA.
EM andy@mail.nih.gov
RI Putnam, Nicholas/B-9968-2008
OI Putnam, Nicholas/0000-0002-1315-782X
FU Intramural Research Program of the National Human Genome Research
Program; National Institutes of Health; NSF [EF-0850294]
FX This work was supported by the Intramural Research Program of the
National Human Genome Research Program, National Institutes of Health.
This work was also supported through NSF grant EF-0850294 to NHP. We
would like to thank Tyra Wolfsberg for her critical reading of this
manuscript, support, and advice throughout this project. We would like
to thank Joseph Ryan for his thoughtful comments and insights regarding
this study. We would like to thank Steve Bond and Shawn Burgess for
their critical reading of the manuscript. We also thank Niraj Trivedi
for his assistance with using the Ingenuity Pathway
Analysis(R) software suite.
NR 63
TC 7
Z9 7
U1 3
U2 19
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2148
J9 BMC EVOL BIOL
JI BMC Evol. Biol.
PD OCT 4
PY 2014
VL 14
AR 212
DI 10.1186/s12862-014-0212-1
PG 17
WC Evolutionary Biology; Genetics & Heredity
SC Evolutionary Biology; Genetics & Heredity
GA AT9LK
UT WOS:000345248700001
PM 25281000
ER
PT J
AU Tran, TM
Aghili, A
Li, SP
Ongoiba, A
Kayentao, K
Doumbo, S
Traore, B
Crompton, PD
AF Tran, Tuan M.
Aghili, Amirali
Li, Shanping
Ongoiba, Aissata
Kayentao, Kassoum
Doumbo, Safiatou
Traore, Boubacar
Crompton, Peter D.
TI A nested real-time PCR assay for the quantification of Plasmodium
falciparum DNA extracted from dried blood spots
SO MALARIA JOURNAL
LA English
DT Article
DE Plasmodium falciparum; Nucleic acid testing; Quantitative PCR; Nested
PCR; Dried blood spot; Passive surveillance
ID POLYMERASE-CHAIN-REACTION; ACQUIRED-IMMUNITY; MALARIA PARASITES;
SENSITIVITY; INFECTIONS; TRIALS; RATES
AB Background: As public health efforts seek to eradicate malaria, there has been an emphasis on eliminating low-density parasite reservoirs in asymptomatic carriers. As such, diagnosing submicroscopic Plasmodium infections using PCR-based techniques has become important not only in clinical trials of malaria vaccines and therapeutics, but also in active malaria surveillance campaigns. However, PCR-based quantitative assays that rely on nucleic acid extracted from dried blood spots (DBS) have demonstrated lower sensitivity than assays that use cryopreserved whole blood as source material.
Methods: The density of Plasmodium falciparum asexual parasites was quantified using genomic DNA extracted from dried blood spots (DBS) and the sensitivity of two approaches was compared: quantitative real-time PCR (qPCR) targeting the P. falciparum 18S ribosomal RNA gene, either with an initial conventional PCR amplification prior to qPCR (nested qPCR), or without an initial amplification (qPCR only). Parasite densities determined by nested qPCR, qPCR only, and light microscopy were compared.
Results: Nested qPCR results in 10-fold higher sensitivity (0.5 parasites/mu l) when compared to qPCR only (five parasites/ul). Among microscopy-positive samples, parasite densities calculated by nested qPCR correlated strongly with microscopy for both asymptomatic (Pearson's r = 0.58, P < 0.001) and symptomatic (Pearson's r = 0.70, P < 0.0001) P. falciparum infections.
Conclusion: Nested qPCR improves the sensitivity for the detection of P. falciparum blood-stage infection from clinical DBS samples. This approach may be useful for active malaria surveillance in areas where submicroscopic asymptomatic infections are prevalent.
C1 [Tran, Tuan M.; Aghili, Amirali; Li, Shanping; Crompton, Peter D.] NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA.
[Ongoiba, Aissata; Kayentao, Kassoum; Doumbo, Safiatou; Traore, Boubacar] Univ Sci Tech & Technol Bamako, Mali Int Ctr Excellence Res, Bamako, Mali.
RP Tran, TM (reprint author), NIAID, Immunogenet Lab, NIH, Twinbrook 2,Room 125,12441 Parklawn Dr, Rockville, MD 20852 USA.
EM tuan.tran@nih.gov
RI Crompton, Peter/N-1130-2016
FU Division of Intramural Research, National Institute of Allergy and
Infectious Diseases, National Institutes of Health
FX We thank the study participants and research support staff in
Kalifabougou and Bamako, Mali. We also thank MR4 for providing the P.
falciparum 18S rRNA PCR plasmid contributed by Dr. Peter A. Zimmerman
(Case Western University). Externally validated DBS samples were kindly
provided by Dr. Steven M. Taylor (Duke University). The Division of
Intramural Research, National Institute of Allergy and Infectious
Diseases, National Institutes of Health supported this work.
NR 19
TC 5
Z9 5
U1 3
U2 5
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1475-2875
J9 MALARIA J
JI Malar. J.
PD OCT 4
PY 2014
VL 13
AR 393
DI 10.1186/1475-2875-13-393
PG 8
WC Infectious Diseases; Parasitology; Tropical Medicine
SC Infectious Diseases; Parasitology; Tropical Medicine
GA AS2OQ
UT WOS:000344119900001
PM 25282516
ER
PT J
AU Nguyen, AB
Clark, TT
AF Nguyen, Anh B.
Clark, Trenette T.
TI The Role of Acculturation and Collectivism in Cancer Screening for
Vietnamese American Women
SO HEALTH CARE FOR WOMEN INTERNATIONAL
LA English
DT Article
ID CERVICAL-CANCER; ASIAN-AMERICAN; SELF-REPORTS; BREAST; CARE;
MAMMOGRAPHY; CALIFORNIA; MORTALITY; ACCESS; PREDICTORS
AB The aim of this study was to examine the influence of demographic variables and the interplay between collectivism and acculturation on breast and cervical cancer screening outcomes among Vietnamese American women. Convenience sampling was used to recruit 111 Vietnamese women from the Richmond, VA, metropolitan area, who participated in a larger cancer screening intervention. All participants completed measures on demographic variables, collectivism, acculturation, and cancer-screening-related variables (i.e., attitudes, self-efficacy, and screening behavior). Findings indicated that collectivism predicted both positive attitudes and higher levels of self-efficacy with regard to breast and cervical cancer screening. Collectivism also moderated the relationship between acculturation and attitudes toward breast cancer screening such that for women with low levels of collectivistic orientation, increasing acculturation predicted less positive attitudes towards breast cancer screening. This relationship was not found for women with high levels of collectivistic orientation. The current findings highlight the important roles that sociodemographic and cultural variables play in affecting health attitudes, self-efficacy, and behavior among Vietnamese women. The findings potentially inform screening programs that rely on culturally relevant values in helping increase Vietnamese women's motivation to screen.
C1 [Nguyen, Anh B.] NCI, Div Canc Control & Populat Sci, Rockville, MD 20850 USA.
[Clark, Trenette T.] Univ N Carolina, Sch Social Work, Chapel Hill, NC USA.
RP Nguyen, AB (reprint author), NCI, Div Canc Control & Populat Sci, 9609 Med Ctr Dr 3E638, Rockville, MD 20850 USA.
EM Anh.Nguyen3@nih.gov
FU NCI NIH HHS [5F31CA136235]; NIDA NIH HHS [K01 DA035895]
NR 61
TC 3
Z9 4
U1 3
U2 5
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA
SN 0739-9332
EI 1096-4665
J9 HEALTH CARE WOMEN IN
JI Health Care Women Int.
PD OCT 3
PY 2014
VL 35
IS 10
BP 1162
EP 1180
DI 10.1080/07399332.2013.863317
PG 19
WC Public, Environmental & Occupational Health; Women's Studies
SC Public, Environmental & Occupational Health; Women's Studies
GA AS6LF
UT WOS:000344374400006
PM 24313445
ER
PT J
AU Didion, JP
Buus, RJ
Naghashfar, Z
Threadgill, DW
Morse, HC
de Villen, FPM
AF Didion, John P.
Buus, Ryan J.
Naghashfar, Zohreh
Threadgill, David W.
Morse, Herbert C., III
de Villen, Fernando Pardo-Manuel
TI SNP array profiling of mouse cell lines identifies their strains of
origin and reveals cross-contamination and widespread aneuploidy
SO BMC GENOMICS
LA English
DT Article
ID COLLABORATIVE CROSS; LABORATORY MOUSE; NUMBER VARIATION; GENOME; MODEL;
IMPROVES; PANEL; END
AB Background: The crisis of Misidentified and contaminated cell lines have plagued the biological research community for decades. Some repositories and journals have heeded calls for mandatory authentication of human cell lines, yet misidentification of mouse cell lines has received little publicity despite their importance in sponsored research. Short tandem repeat (STR) profiling is the standard authentication method, but it may fail to distinguish cell lines derived from the same inbred strain of mice. Additionally, STR profiling does not reveal karyotypic changes that occur in some high-passage lines and may have functional consequences. Single nucleotide polymorphism (SNP) profiling has been suggested as a more accurate and versatile alternative to STR profiling; however, a high-throughput method for SNP-based authentication of mouse cell lines has not been described.
Results: We have developed computational methods (Cell Line Authentication by SNP Profiling, CLASP) for cell line authentication and copy number analysis based on a cost-efficient SNP array, and we provide a reference database of commonly used mouse strains and cell lines. We show that CLASP readily discriminates among cell lines of diverse taxonomic origins, including multiple cell lines derived from a single inbred strain, intercross or wild caught mouse. CLASP is also capable of detecting contaminants present at concentrations as low as 5%. Of the 99 cell lines we tested, 15 exhibited substantial divergence from the reported genetic background. In all cases, we were able to distinguish whether the authentication failure was due to misidentification (one cell line, Ba/F3), the presence of multiple strain backgrounds (five cell lines), contamination by other cells and/or the presence of aneuploid chromosomes (nine cell lines).
Conclusions: Misidentification and contamination of mouse cell lines is potentially as widespread as it is in human cell culture. This may have substantial implications for studies that are dependent on the expected background of their cell cultures. Laboratories can mitigate these risks by regular authentication of their cell cultures. Our results demonstrate that SNP array profiling is an effective method to combat cell line misidentification.
C1 [Didion, John P.; Buus, Ryan J.; de Villen, Fernando Pardo-Manuel] Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA.
[Didion, John P.; Buus, Ryan J.; de Villen, Fernando Pardo-Manuel] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA.
[Didion, John P.; Buus, Ryan J.; de Villen, Fernando Pardo-Manuel] Univ N Carolina, Carolina Ctr Genome Sci, Chapel Hill, NC 27599 USA.
[Naghashfar, Zohreh; Morse, Herbert C., III] NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA.
[Threadgill, David W.] Texas A&M Univ, Coll Vet Med & Biomed Sci, Dept Vet Pathobiol, College Stn, TX 77843 USA.
[Threadgill, David W.] Texas A&M Univ, Coll Med, Dept Mol & Cellular Med, College Stn, TX 77843 USA.
RP Morse, HC (reprint author), NIAID, Immunogenet Lab, NIH, Twinbrook 1,Room 1421,5640 Fishers Lane, Rockville, MD 20852 USA.
EM hmorse@niaid.nih.gov; fernando@med.unc.edu
OI Morse, Herbert/0000-0002-9331-3705; Didion, John/0000-0002-8111-6261
FU Intramural Research Program of the NIH; National Institute of Allergy
and Infectious Diseases; NIH Training Grant [GM067553-04]; NIH [P50
HG006582/MH090338, U54A157157]; University Cancer Research Fund (UNC)
FX We are grateful to Cheryl Ackert-Bicknell, Jennifer Brennan, Dale
Cowley, Rosann Farber, Anne Latour, Beverly Koller, Ron Korstanje, Terry
Magnuson, Steve Murray and Tim Wiltshire for providing us with cell-line
samples, and to Francois Bonhomme, Betina Harr, Michael Nachman, Annie
Orth and Alex Hon-Tsen Yu for providing us with wild mouse samples. We
also thank Mark Callaway, Justin Gooch and Darla Miller for the
management and processing of samples for genotyping. We are grateful to
Drs. Wei Sun and Tatiana Popova for assistance with using genoCN and GAP
software, respectively. Ping Fu, Catie Welsh, Katy Kao and Leonard
McMillan contributed to the design of the MUGA and MegaMUGA arrays. This
work was supported in part by the Intramural Research Program of the
NIH, National Institute of Allergy and Infectious Diseases (ZN, HCM) and
by NIH Training Grant Number GM067553-04 (JPD). JPD was also partially
supported by NIH grant P50 HG006582/MH090338 to FPMV. Additional support
was provided by NIH grants U54A157157 (FPMV) and by the University
Cancer Research Fund (UNC).
NR 33
TC 8
Z9 8
U1 0
U2 8
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 OCT 3
PY 2014
VL 15
AR 847
DI 10.1186/1471-2164-15-847
PG 11
WC Biotechnology & Applied Microbiology; Genetics & Heredity
SC Biotechnology & Applied Microbiology; Genetics & Heredity
GA AQ9MJ
UT WOS:000343178300001
PM 25277546
ER
PT J
AU Ali, M
Chernova, TA
Newnam, GP
Yin, LM
Shanks, J
Karpova, TS
Lee, A
Laur, O
Subramanian, S
Kim, D
McNally, JG
Seyfried, NT
Chernoff, YO
Wilkinson, KD
AF Ali, Moiez
Chernova, Tatiana A.
Newnam, Gary P.
Yin, Luming
Shanks, John
Karpova, Tatiana S.
Lee, Andrew
Laur, Oskar
Subramanian, Sindhu
Kim, Dami
McNally, James G.
Seyfried, Nicholas T.
Chernoff, Yury O.
Wilkinson, Keith D.
TI Stress-dependent Proteolytic Processing of the Actin Assembly Protein
Lsb1 Modulates a Yeast Prion
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
DE Actin; Endoplasmic Reticulum (ER); Prion; Proteasome; Ubiquitylation
(Ubiquitination); Rsp5; Sup35; Heat Shock
ID TAIL-ANCHORED PROTEINS; DAMAGED PROTEINS; IN-VIVO; BUDDING YEAST;
SACCHAROMYCES-CEREVISIAE; QUALITY-CONTROL; CYTOSKELETON; AGGREGATION;
UBIQUITINATION; SEGREGATION
AB Background: Thermal stress affects inheritance of prion amyloids in budding yeast. Results: Heat shock-induced processing of actin assembly protein Lsb1 is involved in yeast prion inheritance. Conclusion: Components of the actin cytoskeleton affect prion dynamics in response to heat shock. Significance: Understanding the mechanisms of aggregate segregation in response to stress may present new opportunities for pharmacological interventions aimed at protein aggregation disorders.
Yeast prions are self-propagating amyloid-like aggregates of Q/N-rich protein that confer heritable traits and provide a model of mammalian amyloidoses. [PSI+] is a prion isoform of the translation termination factor Sup35. Propagation of [PSI+] during cell division under normal conditions and during the recovery from damaging environmental stress depends on cellular chaperones and is influenced by ubiquitin proteolysis and the actin cytoskeleton. The paralogous yeast proteins Lsb1 and Lsb2 bind the actin assembly protein Las17 (a yeast homolog of human Wiskott-Aldrich syndrome protein) and participate in the endocytic pathway. Lsb2 was shown to modulate maintenance of [PSI+] during and after heat shock. Here, we demonstrate that Lsb1 also regulates maintenance of the Sup35 prion during and after heat shock. These data point to the involvement of Lsb proteins in the partitioning of protein aggregates in stressed cells. Lsb1 abundance and cycling between actin patches, endoplasmic reticulum, and cytosol is regulated by the Guided Entry of Tail-anchored proteins pathway and Rsp5-dependent ubiquitination. Heat shock-induced proteolytic processing of Lsb1 is crucial for prion maintenance during stress. Our findings identify Lsb1 as another component of a tightly regulated pathway controlling protein aggregation in changing environments.
C1 [Ali, Moiez; Chernova, Tatiana A.; Yin, Luming; Shanks, John; Lee, Andrew; Subramanian, Sindhu; Kim, Dami; Seyfried, Nicholas T.; Wilkinson, Keith D.] Emory Univ, Dept Biochem, Sch Med, Atlanta, GA 30322 USA.
[Newnam, Gary P.; Chernoff, Yury O.] Georgia Inst Technol, Sch Biol, Atlanta, GA 30332 USA.
[Newnam, Gary P.; Chernoff, Yury O.] Georgia Inst Technol, Parker H Petit Inst Bioengn & Biosci, Atlanta, GA 30332 USA.
[Karpova, Tatiana S.; McNally, James G.] NCI, Ctr Canc Res Core Fluorescence Imaging Facil, Lab Receptor Biol & Gene Express, NIH, Bethesda, MD 20892 USA.
[Laur, Oskar] Emory Univ, Div Microbiol, Yerkes Res Ctr, Atlanta, GA 30329 USA.
[Chernoff, Yury O.] St Petersburg State Univ, Lab Amyloid Biol, St Petersburg 199034, Russia.
RP Chernova, TA (reprint author), 1510 Clifton Rd, Atlanta, GA 30322 USA.
EM tcherno@emory.edu; genekdw@emory.edu
RI Chernoff, Yury/J-2833-2014;
OI Chernoff, Yury/0000-0002-8934-9051
FU National Institutes of Health [GM093294]; St. Petersburg State
University [1.50.2218.2013]
FX This work was supported, in whole or in part, by National Institutes of
Health Grant GM093294 (to K. D. W., T. A. C., and Y. O. C.) and Project
1.50.2218.2013 from St. Petersburg State University (to Y. O. C.).
NR 64
TC 5
Z9 5
U1 1
U2 7
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
EI 1083-351X
J9 J BIOL CHEM
JI J. Biol. Chem.
PD OCT 3
PY 2014
VL 289
IS 40
BP 27625
EP 27639
DI 10.1074/jbc.M114.582429
PG 15
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA AQ5MH
UT WOS:000342852800023
PM 25143386
ER
PT J
AU Amorim, NA
da Silva, EML
de Castro, RO
da Silva-Januario, ME
Mendonca, LM
Bonifacino, JS
da Costa, LJ
daSilva, LLP
AF Amorim, Nathaly A.
da Silva, Eulalia M. L.
de Castro, Rodrigo O.
da Silva-Januario, Mara E.
Mendonca, Luiza M.
Bonifacino, Juan S.
da Costa, Luciana J.
daSilva, Luis L. P.
TI Interaction of HIV-1 Nef Protein with the Host Protein Alix Promotes
Lysosomal Targeting of CD4 Receptor
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
DE Endosome; Human Immunodeficiency Virus (HIV); Intracellular Trafficking;
Lysosome; Protein Sorting; Alix; Multivesicular Body (MVB); Nef
ID VIRUS TYPE-1 NEF; LONG-TERM SURVIVOR; DOWN-REGULATION; CELL-SURFACE;
BETA-COP; INTRACELLULAR TRAFFICKING; MULTIVESICULAR BODIES; VIRAL
REPLICATION; CLATHRIN ADAPTER; SORTING SIGNALS
AB Background: HIV-1 Nef targets the coreceptor CD4 to the multivesicular body (MVB) pathway for degradation via an unknown mechanism. Results: Nef interacts with Alix in late endosomes, and this is required for efficient lysosomal targeting of CD4. Conclusion: Nef utilizes Alix as an adaptor to target CD4 for lysosomal degradation. Significance: The study clarifies the mechanism by which Nef down-regulates expression of specific host-cell proteins.
Nef is an accessory protein of human immunodeficiency viruses that promotes viral replication and progression to AIDS through interference with various host trafficking and signaling pathways. A key function of Nef is the down-regulation of the coreceptor CD4 from the surface of the host cells. Nef-induced CD4 down-regulation involves at least two independent steps as follows: acceleration of CD4 endocytosis by a clathrin/AP-2-dependent pathway and targeting of internalized CD4 to multivesicular bodies (MVBs) for eventual degradation in lysosomes. In a previous work, we found that CD4 targeting to the MVB pathway was independent of CD4 ubiquitination. Here, we report that this targeting depends on a direct interaction of Nef with Alix/AIP1, a protein associated with the endosomal sorting complexes required for transport (ESCRT) machinery that assists with cargo recruitment and intraluminal vesicle formation in MVBs. We show that Nef interacts with both the Bro1 and V domains of Alix. Depletion of Alix or overexpression of the Alix V domain impairs lysosomal degradation of CD4 induced by Nef. In contrast, the V domain overexpression does not prevent cell surface removal of CD4 by Nef or protein targeting to the canonical ubiquitination-dependent MVB pathway. We also show that the Nef-Alix interaction occurs in late endosomes that are enriched in internalized CD4. Together, our results indicate that Alix functions as an adaptor for the ESCRT-dependent, ubiquitin-independent targeting of CD4 to the MVB pathway induced by Nef.
C1 [Amorim, Nathaly A.; da Silva, Eulalia M. L.; de Castro, Rodrigo O.; da Silva-Januario, Mara E.; daSilva, Luis L. P.] Univ Sao Paulo, Ribeirao Preto Sch Med, Dept Cell & Mol Biol, BR-14049900 Ribeirao Preto, SP, Brazil.
[Mendonca, Luiza M.; da Costa, Luciana J.] Univ Fed Rio de Janeiro, Inst Microbiol Paulo de Goes, Dept Virol, BR-21941590 Rio De Janeiro, RJ, Brazil.
[Bonifacino, Juan S.] Eunice Kennedy Shriver NICHD, Cell Biol & Metab Program, NIH, Bethesda, MD 20892 USA.
RP daSilva, LLP (reprint author), Univ Sao Paulo, Ribeirao Preto Sch Med, Dept Cell & Mol Biol, Av Bandeirantes 3900, BR-14049900 Ribeirao Preto, SP, Brazil.
EM lldasilva@fmrp.usp.br
RI LP daSilva, Luis/A-9949-2010;
OI LP daSilva, Luis/0000-0003-3558-0087; Bonifacino, Juan
S./0000-0002-5673-6370
FU National Institutes of Health, NICHD [ZIA HD001607-22]; Sao Paulo
Research Foundation (FAPESP) [2009/50650-6]; Brazilian National Council
for Scientific and Technological Development (CNPq) [470707/2009-7];
Fundacao de Apoio ao Ensino, Pesquisa e Assistencia do Hospital das
Clinicas FMRP-USP (FAEPA); FAPESP
FX This work was supported, in whole or in part, by National Institutes of
Health Grant ZIA HD001607-22 Intramural Program, NICHD (to J. S. B.).
This work was also supported by Sao Paulo Research Foundation (FAPESP)
Young Investigators Grant 2009/50650-6, the Brazilian National Council
for Scientific and Technological Development (CNPq) Grant 470707/2009-7,
and the Fundacao de Apoio ao Ensino, Pesquisa e Assistencia do Hospital
das Clinicas FMRP-USP (FAEPA).; Supported by FAPESP research training
scholarships.
NR 80
TC 10
Z9 11
U1 0
U2 7
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
EI 1083-351X
J9 J BIOL CHEM
JI J. Biol. Chem.
PD OCT 3
PY 2014
VL 289
IS 40
BP 27744
EP 27756
DI 10.1074/jbc.M114.560193
PG 13
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA AQ5MH
UT WOS:000342852800032
PM 25118280
ER
PT J
AU Holland, RJ
Klose, JR
Deschamps, JR
Cao, Z
Keefer, LK
Saavedra, JE
AF Holland, Ryan J.
Klose, John R.
Deschamps, Jeffrey R.
Cao, Zhao
Keefer, Larry K.
Saavedra, Joseph E.
TI Direct Reaction of Amides with Nitric Oxide To Form Diazeniumdiolates
SO JOURNAL OF ORGANIC CHEMISTRY
LA English
DT Article
ID RELEASE; NO; DONORS; CHEMISTRY; AGENTS; HNO
AB We report the apparently unprecedented direct reaction of nitric oxide (NO) with amides to generate ions of structure R(C=O)NH-N(O)=NO-, with examples including R = Me (1a) or 3-pyridyl (1b). The sodium salts of both released NO in pH 7.4 buffer, with 37 degrees C half-lives of 1-3 min. As NO-releasing drug candidates, diazeniumdiolated amides would have the advantage of generating only 1 equiv of base on hydrolyzing exhaustively to NO, in contrast to their amine counterparts, which generate 2 equiv of base.
C1 [Holland, Ryan J.; Keefer, Larry K.] NCI, Drug Design Sect, Biol Chem Lab, Frederick, MD 21702 USA.
[Klose, John R.; Cao, Zhao; Saavedra, Joseph E.] Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
[Deschamps, Jeffrey R.] Naval Res Lab, Ctr Biomol Sci & Engn, Washington, DE 20375 USA.
RP Holland, RJ (reprint author), NCI, Drug Design Sect, Biol Chem Lab, Frederick, MD 21702 USA.
EM hollandrj@mail.nih.gov
RI Keefer, Larry/N-3247-2014
OI Keefer, Larry/0000-0001-7489-9555
FU National Cancer Institute (NCI), National Institutes of Health (NIH)
[HHSN261200800001E]; Intramural Research Program of the NIH, NCI, Center
for Cancer Research; NIDA [Y1-DA1101]; Naval Research Laboratory (NRL)
FX We thank Dr. Sergey Tarasov and Ms. Marzena A. Dyba (Biophysics Resource
in the Structural Biophysics Laboratory, Frederick National Laboratory
for Cancer Research) for assistance with HRMS. This project was funded
by the National Cancer Institute (NCI), National Institutes of Health
(NIH), under Contract HHSN261200800001E, and by the Intramural Research
Program of the NIH, NCI, Center for Cancer Research. The X-ray
crystallographic work was supported by NIDA through Interagency
Agreement #Y1-DA1101 with the Naval Research Laboratory (NRL).
NR 16
TC 2
Z9 2
U1 1
U2 10
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 OCT 3
PY 2014
VL 79
IS 19
BP 9389
EP 9393
DI 10.1021/jo501670e
PG 5
WC Chemistry, Organic
SC Chemistry
GA AQ3US
UT WOS:000342719600047
PM 25210948
ER
PT J
AU Faria, NR
Rambaut, A
Suchard, MA
Baele, G
Bedford, T
Ward, MJ
Tatem, AJ
Sousa, JD
Arinaminpathy, N
Pepin, J
Posada, D
Peeters, M
Pybus, OG
Lemey, P
AF Faria, Nuno R.
Rambaut, Andrew
Suchard, Marc A.
Baele, Guy
Bedford, Trevor
Ward, Melissa J.
Tatem, Andrew J.
Sousa, Joao D.
Arinaminpathy, Nimalan
Pepin, Jacques
Posada, David
Peeters, Martine
Pybus, Oliver G.
Lemey, Philippe
TI The early spread and epidemic ignition of HIV-1 in human populations
SO SCIENCE
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; IMMUNE-DEFICIENCY-SYNDROME; GENETIC
DIVERSITY; NONPANDEMIC HIV-1; CONGO SUGGESTS; SYNDROME AIDS; GROUP-O;
TYPE-1; ORIGIN; STRAINS
AB Thirty years after the discovery of HIV-1, the early transmission, dissemination, and establishment of the virus in human populations remain unclear. Using statistical approaches applied to HIV-1 sequence data from central Africa, we show that from the 1920s Kinshasa (in what is now the Democratic Republic of Congo) was the focus of early transmission and the source of pre-1960 pandemic viruses elsewhere. Location and dating estimates were validated using the earliest HIV-1 archival sample, also from Kinshasa. The epidemic histories of HIV-1 group M and nonpandemic group O were similar until similar to 1960, after which group M underwent an epidemiological transition and outpaced regional population growth. Our results reconstruct the early dynamics of HIV-1 and emphasize the role of social changes and transport networks in the establishment of this virus in human populations.
C1 [Faria, Nuno R.; Arinaminpathy, Nimalan; Pybus, Oliver G.] Univ Oxford, Dept Zool, Oxford OX1 3PS, England.
[Faria, Nuno R.; Baele, Guy; Sousa, Joao D.; Lemey, Philippe] Univ Leuven, KU Leuven, Dept Microbiol & Immunol, Rega Inst Med Res Clin & Epidemiol Virol, B-3000 Leuven, Belgium.
[Rambaut, Andrew; Ward, Melissa J.] Univ Edinburgh, Inst Evolutionary Biol, Ashworth Labs, Edinburgh EH9 3JT, Midlothian, Scotland.
[Rambaut, Andrew; Tatem, Andrew J.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Rambaut, Andrew] Univ Edinburgh, Ctr Immun Infect & Evolut, Edinburgh EH9 3JT, Midlothian, Scotland.
[Suchard, Marc A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Biomath, Los Angeles, CA 90095 USA.
[Suchard, Marc A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Human Genet, Los Angeles, CA 90095 USA.
[Suchard, Marc A.] Univ Calif Los Angeles, UCLA Fielding Sch Publ Hlth, Dept Biostat, Los Angeles, CA 90095 USA.
[Bedford, Trevor] Fred Hutchinson Canc Res Ctr, Vaccine & Infect Dis Div, Seattle, WA 98109 USA.
[Tatem, Andrew J.] Univ Southampton, Dept Geog & Environm, Southampton, Hants, England.
[Sousa, Joao D.] Univ Nova Lisboa, Ctr Malaria & Outras Doencas Tropicais, P-1349008 Lisbon, Portugal.
[Sousa, Joao D.] Univ Nova Lisboa, Unidade Microbiol, Inst Higiene & Med Trop, P-1349008 Lisbon, Portugal.
[Pepin, Jacques] Univ Sherbrooke, Dept Microbiol & Infect Dis, CHUS, Sherbrooke, PQ J1H 5N4, Canada.
[Posada, David] Univ Vigo, Dept Biochem Genet & Immunol, Vigo 36310, Spain.
[Peeters, Martine] Inst Rech Dev, Retrovirus Lab, UMI233, F-34032 Montpellier, France.
[Peeters, Martine] Univ Montpellier, F-34032 Montpellier, France.
RP Pybus, OG (reprint author), Univ Oxford, Dept Zool, S Parks Rd, Oxford OX1 3PS, England.
EM oliver.pybus@zoo.ox.ac.uk; philippe.lemey@rega.kuleuven.be
RI Faria, Nuno/I-2975-2012; Posada, David/C-4502-2008;
OI Faria, Nuno/0000-0001-8839-2798; Posada, David/0000-0003-1407-3406;
Sousa, Joao/0000-0002-7604-3109; Bedford, Trevor/0000-0002-4039-5794;
Pybus, Oliver/0000-0002-8797-2667; Rambaut, Andrew/0000-0003-4337-3707
FU European Union [278433-PREDEMICS]; European Research Council [260864];
"Onderzoeksfonds KU Leuven/Research Fund KU Leuven"; NSF [DMS 1264153,
EF-0423641]; NIH [R01 HG006139]; National Evolutionary Synthesis Center
(NESCent); Wellcome Trust [092807]; Royal Society; Fonds voor
Wetenschappelijk Onderzoek Flanders [G.0692.14]
FX We thank the researchers whose publicly available data made this work
possible and A. M. Vandamme, M. L. Kalish, M. Worobey, and G. Leonard
for helpful discussions. The research leading to these results has
received funding from the European Union Seventh Framework Programme for
research, technological development, and demonstration under grant
agreement no. 278433-PREDEMICS and European Research Council grant
agreement no. 260864. P. L. was partly supported by the "Onderzoeksfonds
KU Leuven/Research Fund KU Leuven." M. A. S. is partly supported by NSF
grant DMS 1264153 and NIH grant R01 HG006139. Collaboration between M.
A. S., A. R., and P. L. was supported by the National Evolutionary
Synthesis Center (NESCent) and NSF grant EF-0423641. This work was
supported by the Wellcome Trust (grant 092807) to A. R. T. B. was
supported by the Royal Society. J.D.S. is partly supported by the Fonds
voor Wetenschappelijk Onderzoek Flanders grant G.0692.14. The data
reported in this paper are deposited in the Dryad Repository
(http://dx.doi.org/10.5061/dryad.nn952). Author contributions: P. L.,
O.G.P., A. R., M. A. S., M. P., and N.R.F. conceived the experiments and
designed the study. N.R.F. and P. L. conducted the phylodynamic
analyses. D. P. performed the recombination analysis and G. B. the model
selection analysis. M. A. S. and T. B. contributed methodology. T. B.,
M.J.W., and N.A. assisted the sequence analysis. J.P., A.J.T., and
J.D.S. contributed historical and spatial data. M. P. provided sequence
data. N.R.F., P. L., O.G.P., and A. R. wrote the paper. All authors
discussed the results and approved the final manuscript. We declare no
competing financial interests.
NR 63
TC 102
Z9 106
U1 24
U2 151
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 OCT 3
PY 2014
VL 346
IS 6205
BP 56
EP 61
DI 10.1126/science.1256739
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AQ0BR
UT WOS:000342446900048
PM 25278604
ER
PT J
AU Mumford, SL
Michels, KA
Salaria, N
Valanzasca, P
Belizan, JM
AF Mumford, Sunni L.
Michels, Kara A.
Salaria, Natasha
Valanzasca, Pilar
Belizan, Jose M.
TI Preconception care: it's never too early
SO REPRODUCTIVE HEALTH
LA English
DT Editorial Material
ID HEALTH; REPRODUCTION; PREGNANCY; FERTILITY; DESIGN; RISKS
AB The preconception window has been recognized as one of the earliest sensitive windows of human development, and interventions that focus on this period have the potential to affect not only pregnancy but long term outcomes as well. The journal Reproductive Health has published a supplement entitled 'Preconception Interventions' which includes a series of systematic reviews regarding the impact of public health interventions during the preconception period on maternal and child health. These articles describe the role that poor preconception health plays in creating health disparities across the globe. The reviews highlight our current understanding (or lack thereof) regarding how both maternal and paternal preconception health and knowledge shapes the long-term health of not only children, but of families, communities, and nations. Researchers and healthcare workers should take particular note of these interventions, as the preconception time period may be as important as the pregnancy and post-pregnancy periods, and is critical in terms of bridging the gap in the continuum of care, particularly for adolescents.
C1 [Mumford, Sunni L.; Michels, Kara A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Intramural Populat Hlth Res, NIH, Rockville, MD 20852 USA.
[Salaria, Natasha] BioMed Cent, London, England.
[Valanzasca, Pilar; Belizan, Jose M.] Inst Clin Effectiveness & Hlth Policy, Buenos Aires, DF, Argentina.
RP Mumford, SL (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Intramural Populat Hlth Res, NIH, 6100 Execut Blvd 7B03, Rockville, MD 20852 USA.
EM mumfords@mail.nih.gov
OI Michels, Kara/0000-0003-2431-2079; Belizan, Jose/0000-0002-8412-3010
FU Intramural NIH HHS
NR 18
TC 0
Z9 0
U1 1
U2 4
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1742-4755
J9 REPROD HEALTH
JI Reprod. Health
PD OCT 2
PY 2014
VL 11
AR 73
DI 10.1186/1742-4755-11-73
PG 3
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA AX2UP
UT WOS:000346800700001
PM 25273543
ER
PT J
AU Godley, SH
Smith, JE
Passetti, LL
Subramaniam, G
AF Godley, Susan H.
Smith, Jane Ellen
Passetti, Lora L.
Subramaniam, Geetha
TI The Adolescent Community Reinforcement Approach (A-CRA) as a Model
Paradigm for the Management of Adolescents With Substance Use Disorders
and Co-Occurring Psychiatric Disorders
SO SUBSTANCE ABUSE
LA English
DT Review
DE substance use treatment; co-occurring psychiatric disorders;
co-occurring disorders; integrated treatment; Adolescent; Adolescent
Community Reinforcement Approach
ID RANDOMIZED CONTROLLED-TRIAL; COGNITIVE-BEHAVIORAL-THERAPY;
ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; ASSERTIVE CONTINUING CARE;
DRUG-ABUSE TREATMENT; MENTAL-HEALTH; TREATMENT OUTCOMES;
RESIDENTIAL-TREATMENT; DEPRESSIVE SYMPTOMS; MAJOR DEPRESSION
AB ABSTRACT. Background: Integrated treatment for youth with substance use disorders (SUDs) and co-occurring psychiatric disorders is recommended; however, there are few studies that have evaluated integrated treatment approaches. Methods: This paper includes a brief review of cognitive-behavioral and family therapies, since they have been demonstrated to be effective treatments for the disorders that commonly co-occur with substance use. It also describes how an integrated treatment paradigm has been implemented using one Empirically Supported Treatment, the Adolescent Community Reinforcement Approach (A-CRA). Results: There is existing research that supports the use of several A-CRA procedures to treat substance use and commonly co-occurring psychiatric disorders. Conclusions: In the absence of further research, it is reasonable in the interim to train clinicians in treatments that incorporate components that have been found to be effective for both substance use and commonly co-occurring psychiatric disorders. These treatments can then be adapted as needed based on an individual youth's set of problems. Further research is needed to test treatments for various combinations of SUDs and psychiatric disorders (i.e., depression, trauma-related problems, conduct disorder/behavior problems, and attention-deficit/hyperactivity disorder [ADHD]).
C1 [Godley, Susan H.; Passetti, Lora L.] Chestnut Hlth Syst, Normal, IL 61761 USA.
[Smith, Jane Ellen] Univ New Mexico, Dept Psychol, Albuquerque, NM 87131 USA.
[Subramaniam, Geetha] NIDA, Ctr Clin Trials Network, Bethesda, MD 20892 USA.
[Subramaniam, Geetha] Johns Hopkins Univ, Sch Med, Baltimore, MD USA.
RP Godley, SH (reprint author), Chestnut Hlth Syst, 448 Wylie Dr, Normal, IL 61761 USA.
EM sgodley@chestnut.org
FU Center for Substance Abuse Treatment (CSAT); Substance Abuse and Mental
Health Services Administration (SAMHSA); US Department of Health and
Human Services (DHHS) [270-07-0191]
FX Preparation of the manuscript was supported by funding from the Center
for Substance Abuse Treatment (CSAT), Substance Abuse and Mental Health
Services Administration (SAMHSA), and the US Department of Health and
Human Services (DHHS) (contract no. 270-07-0191). 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 111
TC 6
Z9 6
U1 1
U2 24
PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD
PI ABINGDON
PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND
SN 0889-7077
EI 1547-0164
J9 SUBST ABUS
JI Subst. Abus.
PD OCT 2
PY 2014
VL 35
IS 4
SI SI
BP 352
EP 363
DI 10.1080/08897077.2014.936993
PG 12
WC Substance Abuse
SC Substance Abuse
GA AW3MO
UT WOS:000346191100005
PM 25035906
ER
PT J
AU Kirk, JL
Fay, MP
AF Kirk, Jennifer L.
Fay, Michael P.
TI An Introduction to Practical Sequential Inferences via Single-Arm Binary
Response Studies Using the binseqtest R Package
SO AMERICAN STATISTICIAN
LA English
DT Article
DE Two-stage design; Sequential test; Phase II trial; Exact method; Early
closeout; Adaptive design; Overrunning
ID CANCER CLINICAL-TRIALS; 2-STAGE DESIGNS; TESTS
AB We review sequential designs, including group sequential and two-stage designs, for testing or estimating a single binary parameter. We use this simple case to introduce ideas common to many sequential designs, which in this case can be explained without explicitly using stochastic processes. We focus on methods provided by our newly developed R package, binseqtest, which exactly bound the Type I error rate of tests and exactly maintain proper coverage of confidence intervals. Within this framework, we review some allowable practical adaptations of the sequential design. We explore issues such as the following: How should the design be modified if no assessment was made at one of the planned sequential stopping times? How should the parameter be estimated if the study needs to be stopped early? What reasons for stopping early are allowed? How should inferences be made when the study is stopped for crossing the boundary, but later information is collected about responses of subjects that had enrolled before the decision to stop but had not responded by that time? Answers to these questions are demonstrated using basic methods that are available in our binseqtest R package. Supplementary materials for this article are available online.
C1 [Kirk, Jennifer L.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
[Kirk, Jennifer L.; Fay, Michael P.] NIAID, Bethesda, MD 20892 USA.
RP Kirk, JL (reprint author), Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
EM jlkirk@uw.edu; mfay@niaid.nih.gov
OI Fay, Michael P./0000-0002-8643-9625
NR 22
TC 1
Z9 1
U1 0
U2 2
PU AMER STATISTICAL ASSOC
PI ALEXANDRIA
PA 732 N WASHINGTON ST, ALEXANDRIA, VA 22314-1943 USA
SN 0003-1305
EI 1537-2731
J9 AM STAT
JI Am. Stat.
PD OCT 2
PY 2014
VL 68
IS 4
BP 230
EP 242
DI 10.1080/00031305.2014.951126
PG 13
WC Statistics & Probability
SC Mathematics
GA AT7TE
UT WOS:000345139300002
ER
PT J
AU Bonham, VL
Sellers, SL
Woolford, S
AF Bonham, Vence L.
Sellers, Sherrill L.
Woolford, Sam
TI Physicians' knowledge, beliefs, and use of race and human genetic
variation: new measures and insights
SO BMC HEALTH SERVICES RESEARCH
LA English
DT Article
DE Scale development; Medical decision making; Personalized medicine; RACE
(Racial Attributes in Clinical Evaluation); GKAI (Genetic Variation
Knowledge Assessment Index); Explicit use of race
ID DECISION-MAKING; PUBLIC-HEALTH; DISPARITIES; ANCESTRY; PATIENT;
RACE/ETHNICITY; ATTITUDES; MEDICINE; DISEASE; GENDER
AB Background: Understanding physician perspectives on the intersection of race and genomics in clinical decision making is critical as personalized medicine and genomics become more integrated in health care services. There is a paucity of literature in the United States of America (USA) and globally regarding how health care providers understand and use information about race, ethnicity and genetic variation in their clinical decision making. This paper describes the development of three scales related to addressing this gap in the literature: the Bonham and Sellers Genetic Variation Knowledge Assessment Index-GKAI, Health Professionals Beliefs about Race-HPBR, and Racial Attributes in Clinical Evaluation RACE scales.
Methods: A cross-sectional, web survey of a national random sample of general internists in the USA (N = 787) was conducted. Confirmatory factor analysis was used to assess the construct validity of the scales. Scale items were developed through focus groups, cognitive interviews, expert advisory panels, and exploratory factor analysis of pilot data.
Results: GKAI was measured as a count of correct answers (Mean = 3.28 SD = 1.17). HPBR yielded two domains: beliefs about race as a biological phenomenon (HPBR-BD, alpha = .69, 4 items) and beliefs about the clinical value of race and genetic variation for understanding risk for disease (HPBR-CD alpha = .61, 3 items). RACE yielded one factor (alpha = .86, 7 items).
Conclusions: GKAI is a timely knowledge scale that can be used to assess health professional knowledge of race and human genetic variation. HPBR is a promising new tool for assessing health professionals' beliefs about the role of race and its relationship with human genetic variation in clinical practice. RACE offers a valid and reliable tool for assessing explicit use of racial attributes in clinical decision making.
C1 [Bonham, Vence L.] NHGRI, Social & Behav Res Branch, NIH, Bethesda, MD 20892 USA.
[Sellers, Sherrill L.] Miami Univ, Univ Dept Family Studies & Social Work, Oxford, OH 45056 USA.
[Woolford, Sam] Bentley Univ, Dept Math Sci, Ctr Quantitat Anal, Waltham, MA USA.
RP Bonham, VL (reprint author), NHGRI, Social & Behav Res Branch, NIH, 31 Ctr Dr, Bethesda, MD 20892 USA.
EM bonhamv@nhgri.nih.gov; slsellers@miamioh.edu
FU Intramural Research Program of the National Human Genome Research
Institute, National Institutes of Health [ZIA HG200324-07]
FX This research was supported [in part] by the Intramural Research Program
of the National Human Genome Research Institute, National Institutes of
Health (ZIA HG200324-07).
NR 45
TC 5
Z9 5
U1 0
U2 13
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1472-6963
J9 BMC HEALTH SERV RES
JI BMC Health Serv. Res.
PD OCT 2
PY 2014
VL 14
AR 456
DI 10.1186/1472-6963-14-456
PG 11
WC Health Care Sciences & Services
SC Health Care Sciences & Services
GA AR6FO
UT WOS:000343679000001
PM 25277068
ER
PT J
AU Lai, CH
Park, KS
Lee, DH
Alberobello, AT
Raffeld, M
Pierobon, M
Pin, E
Petricoin, EF
Wang, Y
Giaccone, G
AF Lai, C-H
Park, K-S
Lee, D-H
Alberobello, A. T.
Raffeld, M.
Pierobon, M.
Pin, E.
Petricoin, E. F., III
Wang, Y.
Giaccone, G.
TI HSP-90 inhibitor ganetespib is synergistic with doxorubicin in small
cell lung cancer
SO ONCOGENE
LA English
DT Article
DE doxorubicin; Ganetespib; hsp90 inhibitor; rip1; SCLC
ID KAPPA-B ACTIVATION; POTENT ANTITUMOR-ACTIVITY; HSP90 INHIBITOR;
SIGNALING PATHWAYS; PROTEIN; APOPTOSIS; CYCLOPHOSPHAMIDE; VINCRISTINE;
DEATH; CISPLATIN
AB Small cell lung cancer (SCLC) at advanced stage is considered an incurable disease. Despite good response to initial chemotherapy, the responses in SCLC patients with metastatic disease are of short duration and resistance inevitably occurs. Although several target-specific drugs have altered the paradigm of treatment for many other cancers, we have yet to witness a revolution of the same magnitude in SCLC treatment. Anthracyclines, such as doxorubicin, have definite activity in this disease, and ganetespib has shown promising activity in preclinical models but underwhelming activity as a single agent in SCLC patients. Using SCLC cell lines, we demonstrated that ganetespib (IC50: 31 nM) was much more potent than 17-allylamino-17-demethoxygeldanamycin (17-AAG), a geldanamycin derivative (IC50: 16 mu M). Ganetespib inhibited SCLC cell growth via induction of persistent G2/M arrest and Caspase 3-dependent cell death. MTS assay revealed that ganetespib synergized with both doxorubicin and etoposide, two topoisomerase II inhibitors commonly used in SCLC chemotherapy. Expression of receptor-interacting serine/threonine-protein kinase 1 (RIP1), a protein that may function as a pro-survival scaffold protein or a pro-death kinase in TNFR1-activated cells, was induced by doxorubicin and downregulated by ganetespib. Depletion of RIP1 by either RIP1 small interfering RNA (siRNA) or ganetespib sensitized doxorubicin-induced cell death, suggesting that RIP1 may promote survival in doxorubicin-treated cells and that ganetespib may synergize with doxorubicin in part through the downregulation of RIP1. In comparison to ganetespib or doxorubicin alone, the ganetespib + doxorubicin combination caused significantly more growth regression and death of human SCLC xenografts in immunocompromised mice. We conclude that ganetespib and doxorubicin combination exhibits significant synergy and is efficacious in inhibiting SCLC growth in vitro and in mouse xenograft models. Our preclinical study suggests that ganetespib and doxorubicin combination therapy may be an effective strategy for SCLC treatment, which warrants clinical testing.
C1 [Lai, C-H; Park, K-S; Lee, D-H; Alberobello, A. T.; Wang, Y.; Giaccone, G.] NCI, Med Oncol Branch, NIH, Bethesda, MD USA.
[Raffeld, M.] NCI, Pathol Lab, NIH, Bethesda, MD USA.
[Pierobon, M.; Pin, E.; Petricoin, E. F., III] George Masson Univ, Ctr Appl Prote & Mol Med, Manassas, VI USA.
RP Wang, Y (reprint author), Georgetown Univ, Lombardi Comprehens Canc Ctr, 3970 Reservoir Rd NW,W503 Res Bldg, Washington, DC 20007 USA.
EM yw350@georgetown.edu; gg496@georgetown.edu
RI Giaccone, Giuseppe/E-8297-2017
OI Giaccone, Giuseppe/0000-0002-5023-7562
FU National Cancer Institute
FX We thank Dr Leonard M Neckers for stimulating discussion during the
course of the study and Dr Weiwen Ying (Synta Pharmaceuticals) for his
valuable comments on the manuscript and for providing ganetespib for the
study. This research was funded by the National Cancer Institute
Intramural Program.
NR 53
TC 15
Z9 17
U1 0
U2 14
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 OCT 2
PY 2014
VL 33
IS 40
BP 4867
EP 4876
DI 10.1038/onc.2013.439
PG 10
WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
GA AR0EH
UT WOS:000343240100008
PM 24166505
ER
PT J
AU Bhatia, G
Tandon, A
Patterson, N
Aldrich, MC
Ambrosone, CB
Amos, C
Bandera, EV
Berndt, SI
Bernstein, L
Blot, WJ
Bock, CH
Caporaso, N
Casey, G
Deming, SL
Diver, WR
Gapstur, SM
Gillanders, EM
Harris, CC
Henderson, BE
Ingles, SA
Isaacs, W
De Jager, PL
John, EM
Kittles, RA
Larkin, E
McNeill, LH
Millikan, RC
Murphy, A
Neslund-Dudas, C
Nyante, S
Press, MF
Rodriguez-Gil, JL
Rybicki, BA
Schwartz, AG
Signorello, LB
Spitz, M
Strom, SS
Tucker, MA
Wiencke, JK
Witte, JS
Wu, X
Yamamura, Y
Zanetti, KA
Zheng, W
Ziegler, RG
Chanock, SJ
Haiman, CA
Reich, D
Price, AL
AF Bhatia, Gaurav
Tandon, Arti
Patterson, Nick
Aldrich, Melinda C.
Ambrosone, Christine B.
Amos, Christopher
Bandera, Elisa V.
Berndt, Sonja I.
Bernstein, Leslie
Blot, William J.
Bock, Cathryn H.
Caporaso, Neil
Casey, Graham
Deming, Sandra L.
Diver, W. Ryan
Gapstur, Susan M.
Gillanders, Elizabeth M.
Harris, Curtis C.
Henderson, Brian E.
Ingles, Sue A.
Isaacs, William
De Jager, Phillip L.
John, Esther M.
Kittles, Rick A.
Larkin, Emma
McNeill, Lorna H.
Millikan, Robert C.
Murphy, Adam
Neslund-Dudas, Christine
Nyante, Sarah
Press, Michael F.
Rodriguez-Gil, Jorge L.
Rybicki, Benjamin A.
Schwartz, Ann G.
Signorello, Lisa B.
Spitz, Margaret
Strom, Sara S.
Tucker, Margaret A.
Wiencke, John K.
Witte, John S.
Wu, Xifeng
Yamamura, Yuko
Zanetti, Krista A.
Zheng, Wei
Ziegler, Regina G.
Chanock, Stephen J.
Haiman, Christopher A.
Reich, David
Price, Alkes L.
TI Genome-wide Scan of 29,141 African Americans Finds No Evidence of
Directional Selection since Admixture
SO AMERICAN JOURNAL OF HUMAN GENETICS
LA English
DT Article
ID ESTIMATING F-STATISTICS; NATURAL-SELECTION; POSITIVE SELECTION;
LOCAL-ANCESTRY; POPULATION-STRUCTURE; ALTITUDE ADAPTATION; LATINO
POPULATIONS; VARIANTS; GENE; SIGNALS
AB The extent of recent selection in admixed populations is currently an unresolved question. We scanned the genomes of 29,141 African Americans and failed to find any genome-wide-significant deviations in local ancestry, indicating no evidence of selection influencing ancestry after admixture. A recent analysis of data from 1,890 African Americans reported that there was evidence of selection in African Americans after their ancestors left Africa, both before and after admixture. Selection after admixture was reported on the basis of deviations in local ancestry, and selection before admixture was reported on the basis of allele-frequency differences between African Americans and African populations. The local-ancestry deviations reported by the previous study did not replicate in our very large sample, and we show that such deviations were expected purely by chance, given the number of hypotheses tested. We further show that the previous study's conclusion of selection in African Americans before admixture is also subject to doubt. This is because the F-ST statistics they used were inflated and because true signals of unusual allele-frequency differences between African Americans and African populations would be best explained by selection that occurred in Africa prior to migration to the Americas.
C1 [Bhatia, Gaurav] Harvard MIT Program Hlth Sci & Technol, Div Hlth Sci & Technol, Cambridge, MA 02139 USA.
[Bhatia, Gaurav; Tandon, Arti; Patterson, Nick; De Jager, Phillip L.; Reich, David; Price, Alkes L.] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.
[Tandon, Arti; De Jager, Phillip L.; Reich, David] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Aldrich, Melinda C.; Blot, William J.; Deming, Sandra L.; Signorello, Lisa B.; Zheng, Wei] Vanderbilt Epidemiol Ctr, Div Epidemiol, Dept Med, Nashville, TN 37203 USA.
[Aldrich, Melinda C.; Blot, William J.; Deming, Sandra L.; Signorello, Lisa B.; Zheng, Wei] Vanderbilt Univ, Vanderbilt Ingram Canc Ctr, Sch Med, Nashville, TN 37203 USA.
[Aldrich, Melinda C.] Vanderbilt Univ, Dept Thorac Surg, Sch Med, Nashville, TN 37203 USA.
[Ambrosone, Christine B.] Roswell Pk Canc Inst, Dept Canc Prevent & Control, Buffalo, NY 14263 USA.
[Amos, Christopher; Spitz, Margaret; Wu, Xifeng] Dartmouth Coll, Geisel Sch Med, Sect Biostat & Epidemiol Community & Family Med, Hanover, NH 03766 USA.
[Bandera, Elisa V.] Rutgers Canc Inst New Jersey, New Brunswick, NJ 08903 USA.
[Berndt, Sonja I.; Caporaso, Neil; Tucker, Margaret A.; Ziegler, Regina G.; Chanock, Stephen J.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Bernstein, Leslie] City Hope Natl Med Ctr, Beckman Res Inst, Dept Populat Sci, Div Canc Etiol, Duarte, CA 91010 USA.
[Blot, William J.; Signorello, Lisa B.] Int Epidemiol Inst, Rockville, MD 20850 USA.
[Bock, Cathryn H.; Schwartz, Ann G.] Wayne State Univ Med, Karmanos Canc Inst, Detroit, MI 48201 USA.
[Bock, Cathryn H.; Schwartz, Ann G.] Wayne State Univ Med, Dept Oncol, Detroit, MI 48201 USA.
[Casey, Graham; Henderson, Brian E.; Ingles, Sue A.; Press, Michael F.; Haiman, Christopher A.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Norris Comprehens Canc Ctr, Los Angeles, CA 90033 USA.
[Casey, Graham; Henderson, Brian E.; Ingles, Sue A.; Press, Michael F.; Haiman, Christopher A.] Univ So Calif, Keck Sch Med, Dept Pathol, Norris Comprehens Canc Ctr, Los Angeles, CA 90033 USA.
[Diver, W. Ryan; Gapstur, Susan M.] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30303 USA.
[Gillanders, Elizabeth M.; Zanetti, Krista A.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Harris, Curtis C.; Zanetti, Krista A.] NCI, Lab Human Carcinogenesis, Ctr Canc Res, Bethesda, MD 20892 USA.
[Isaacs, William] Johns Hopkins Hosp & Med Inst, James Buchanan Brady Urol Inst, Baltimore, MD 21287 USA.
[De Jager, Phillip L.] Brigham & Womens Hosp, Inst Neurosci, Dept Neurol, Program Translat NeuroPsychiat Genom, Boston, MA 02115 USA.
[John, Esther M.] Canc Prevent Inst Calif, Fremont, CA 94538 USA.
[John, Esther M.] Stanford Med, Stanford Canc Ctr, Stanford, CA 94305 USA.
[Kittles, Rick A.] Univ Illinois, Dept Med, Chicago, IL 60607 USA.
[Larkin, Emma] Vanderbilt Univ Sch Med, Dept Med, Div Allergy Pulm & Crit Care, Nashville, TN 37232 USA.
[McNeill, Lorna H.] Univ Texas MD Anderson Canc Ctr, Dept Hlth Dispar Res Canc Prevent & Populat Sci, Houston, TX 77030 USA.
[McNeill, Lorna H.] Univ Texas MD Anderson Canc Ctr, Duncan Family Inst, Ctr Community Implementat & Disseminat Res, Houston, TX 77030 USA.
[Millikan, Robert C.; Nyante, Sarah] Univ N Carolina, Gillings Sch Global Publ Hlth, Dept Epidemiol, Chapel Hill, NC 27599 USA.
[Millikan, Robert C.; Nyante, Sarah] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA.
[Murphy, Adam] Northwestern Univ, Dept Urol, Chicago, IL 60611 USA.
[Neslund-Dudas, Christine; Rybicki, Benjamin A.] Henry Ford Hosp, Dept Publ Hlth Sci, Detroit, MI 48202 USA.
[Rodriguez-Gil, Jorge L.] Univ Miami, Sylvester Comprehens Canc Ctr, Miller Sch Med, Miami, FL 33136 USA.
[Rodriguez-Gil, Jorge L.] Univ Miami, Dept Epidemiol & Publ Hlth, Miller Sch Med, Miami, FL 33136 USA.
[Strom, Sara S.; Yamamura, Yuko] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA.
[Wiencke, John K.] Univ Calif San Francisco, San Francisco, CA 94158 USA.
[Witte, John S.] Univ Calif San Francisco, Inst Human Genet, Dept Epidemiol & Biostat, San Francisco, CA 94158 USA.
[Witte, John S.] Univ Calif San Francisco, Inst Human Genet, Dept Urol, San Francisco, CA 94158 USA.
[Price, Alkes L.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Price, Alkes L.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
RP Bhatia, G (reprint author), Harvard MIT Program Hlth Sci & Technol, Div Hlth Sci & Technol, Cambridge, MA 02139 USA.
EM gbhatia@mit.edu
RI Tucker, Margaret/B-4297-2015; Bandera, Elisa/M-4169-2014
OI Bandera, Elisa/0000-0002-8789-2755
FU NIH [R01 HG006399]
FX We thank Carlos Bustamante, Bogdan Pasaniuc, and Amy L. Williams for
helpful discussions and Richard Cooper for sharing data from 756 Yoruba
samples. This research was funded by NIH grant R01 HG006399.
NR 41
TC 15
Z9 15
U1 0
U2 15
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 OCT 2
PY 2014
VL 95
IS 4
BP 437
EP 444
DI 10.1016/j.ajhg.2014.08.011
PG 8
WC Genetics & Heredity
SC Genetics & Heredity
GA AQ2XW
UT WOS:000342654300008
PM 25242497
ER
PT J
AU Skibola, CF
Berndt, SI
Vijai, J
Conde, L
Wang, ZM
Yeager, M
de Bakker, PIW
Birmann, BM
Vajdic, CM
Foo, JN
Bracci, PM
Vermeulen, RCH
Slager, SL
de Sanjose, S
Wang, SS
Linet, MS
Salles, G
Lan, Q
Severi, G
Hjalgrim, H
Lightfoot, T
Melbye, M
Gu, J
Ghesquieres, H
Link, BK
Morton, LM
Holly, EA
Smith, A
Tinker, LF
Teras, LR
Kricker, A
Becker, N
Purdue, MP
Spinelli, JJ
Zhang, YW
Giles, GG
Vineis, P
Monnereau, A
Bertrand, KA
Albanes, D
Zeleniuch-Jacquotte, A
Gabbas, A
Chung, CC
Burdett, L
Hutchinson, A
Lawrence, C
Montalvan, R
Liang, LM
Huang, JY
Ma, BS
Liu, JJ
Adami, HO
Glimelius, B
Ye, YQ
Nowakowski, GS
Dogan, A
Thompson, CA
Habermann, TM
Novak, AJ
Liebow, M
Witzig, TE
Weiner, GJ
Schenk, M
Hartge, P
De Roos, AJ
Cozen, W
Zhi, DG
Akers, NK
Riby, J
Smith, MT
Lacher, M
Villano, DJ
Maria, A
Roman, E
Kane, E
Jackson, RD
North, KE
Diver, WR
Turner, J
Armstrong, BK
Benavente, Y
Boffetta, P
Brennan, P
Foretova, L
Maynadie, M
Staines, A
McKay, J
Brooks-Wilson, AR
Zheng, TZ
Holford, TR
Chamosa, S
Kaaks, R
Kelly, RS
Ohlsson, B
Travis, RC
Weiderpass, E
Clave, J
Giovannucci, E
Kraft, P
Virtamo, J
Mazza, P
Cocco, P
Ennas, MG
Chiu, BCH
Fraumeni, JR
Nieters, A
Offit, K
Wu, XF
Cerhan, JR
Smedby, KE
Chanock, SJ
Rothman, N
AF Skibola, Christine F.
Berndt, Sonja I.
Vijai, Joseph
Conde, Lucia
Wang, Zhaoming
Yeager, Meredith
de Bakker, Paul I. W.
Birmann, Brenda M.
Vajdic, Claire M.
Foo, Jia-Nee
Bracci, Paige M.
Vermeulen, Roel C. H.
Slager, Susan L.
de Sanjose, Silvia
Wang, Sophia S.
Linet, Martha S.
Salles, Gilles
Lan, Qing
Severi, Gianluca
Hjalgrim, Henrik
Lightfoot, Tracy
Melbye, Mads
Gu, Jian
Ghesquieres, Herve
Link, Brian K.
Morton, Lindsay M.
Holly, Elizabeth A.
Smith, Alex
Tinker, Lesley F.
Teras, Lauren R.
Kricker, Anne
Becker, Nikolaus
Purdue, Mark P.
Spinelli, John J.
Zhang, Yawei
Giles, Graham G.
Vineis, Paolo
Monnereau, Alain
Bertrand, Kimberly A.
Albanes, Demetrius
Zeleniuch-Jacquotte, Anne
Gabbas, Attilio
Chung, Charles C.
Burdett, Laurie
Hutchinson, Amy
Lawrence, Charles
Montalvan, Rebecca
Liang, Liming
Huang, Jinyan
Ma, Baoshan
Liu, Jianjun
Adami, Hans-Olov
Glimelius, Bengt
Ye, Yuanqing
Nowakowski, Grzegorz S.
Dogan, Ahmet
Thompson, Carrie A.
Habermann, Thomas M.
Novak, Anne J.
Liebow, Mark
Witzig, Thomas E.
Weiner, George J.
Schenk, Maryjean
Hartge, Patricia
De Roos, Anneclaire J.
Cozen, Wendy
Zhi, Degui
Akers, Nicholas K.
Riby, Jacques
Smith, Martyn T.
Lacher, Mortimer
Villano, Danylo J.
Maria, Ann
Roman, Eve
Kane, Eleanor
Jackson, Rebecca D.
North, Kari E.
Diver, W. Ryan
Turner, Jenny
Armstrong, Bruce K.
Benavente, Yolanda
Boffetta, Paolo
Brennan, Paul
Foretova, Lenka
Maynadie, Marc
Staines, Anthony
McKay, James
Brooks-Wilson, Angela R.
Zheng, Tongzhang
Holford, Theodore R.
Chamosa, Saioa
Kaaks, Rudolph
Kelly, Rachel S.
Ohlsson, Bodil
Travis, Ruth C.
Weiderpass, Elisabete
Clave, Jacqueline
Giovannucci, Edward
Kraft, Peter
Virtamo, Jarmo
Mazza, Patrizio
Cocco, Pierluigi
Ennas, Maria Grazia
Chiu, Brian C. H.
Fraumeni, Joseph R., Jr.
Nieters, Alexandra
Offit, Kenneth
Wu, Xifeng
Cerhan, James R.
Smedby, Karin E.
Chanock, Stephen J.
Rothman, Nathaniel
TI Genome-wide Association Study Identifies Five Susceptibility Loci for
Follicular Lymphoma outside the HLA Region
SO AMERICAN JOURNAL OF HUMAN GENETICS
LA English
DT Article
ID CLASS-I; VARIANTS; EXPRESSION; UNIVERSITY; RESOURCE; PEPTIDE; RISK;
SNPS; TOOL; SET
AB Genome-wide association studies (GWASs) of follicular lymphoma (FL) have previously identified human leukocyte antigen (HLA) gene variants. To identify additional FL susceptibility loci, we conducted a large-scale two-stage GWAS in 4,523 case subjects and 13,344 control subjects of European ancestry. Five non-HLA loci were associated with FL risk: 11q23.3 (rs4938573, p = 5.79 x 10(-20)) near CXCR5; 11q24.3 (rs4937362, p = 6.76 x 10(-11)) near ETS1; 3q28 (rs6444305, p = 1.10 x 10(-10)) in LPP; 18q21.33 (rs17749561, p = 8.28 x 10(-10)) near BCL2; and 8q24.21 (rs13254990, p = 1.06 x 10(-8)) near PVT1. In an analysis of the HLA region, we identified four linked HLA-DR beta 1 multiallelic amino acids at positions 11, 13, 28, and 30 that were associated with FL risk (P-omnibus = 4.20 x 10(-67) to 2.67 x 10(-70)). Additional independent signals included rs17203612 in HLA class II (odds ratio [ORper-allele] = 1.44; p = 4.59 x 10(-16)) and rs3130437 in HLA class I (ORper-allele = 1.23; p = 8.23 x 10(-9)). Our findings further expand the number of loci associated with FL and provide evidence that multiple common variants outside the HLA region make a significant contribution to FL risk.
C1 [Skibola, Christine F.; Conde, Lucia; Riby, Jacques] Sch Publ Hlth, Dept Epidemiol, Birmingham, AL 35233 USA.
[Skibola, Christine F.; Conde, Lucia; Riby, Jacques] Ctr Comprehens Canc, Birmingham, AL 35233 USA.
[Skibola, Christine F.; Conde, Lucia; Akers, Nicholas K.; Riby, Jacques; Smith, Martyn T.] Univ Calif Berkeley, Sch Publ Hlth, Div Environm Hlth Sci, Berkeley, CA 94720 USA.
[Berndt, Sonja I.; Linet, Martha S.; Lan, Qing; Morton, Lindsay M.; Purdue, Mark P.; Albanes, Demetrius; Chung, Charles C.; Hartge, Patricia; Fraumeni, Joseph R., Jr.; Chanock, Stephen J.; Rothman, Nathaniel] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Vijai, Joseph; Lacher, Mortimer; Villano, Danylo J.; Maria, Ann; Offit, Kenneth] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10065 USA.
[Wang, Zhaoming; Yeager, Meredith; Burdett, Laurie; Hutchinson, Amy] NCI, Cancer Genom Res Lab, Div Canc Epidemiol & Genet, NIH, Gaithersburg, MD 20877 USA.
[de Bakker, Paul I. W.] Univ Med Ctr Utrecht, Dept Med Genet & Epidemiol, NL-3584 CG Utrecht, Netherlands.
[de Bakker, Paul I. W.; Vermeulen, Roel C. H.] Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, NL-3584 CX Utrecht, Netherlands.
[Birmann, Brenda M.; Bertrand, Kimberly A.; Giovannucci, Edward] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA.
[Birmann, Brenda M.; Bertrand, Kimberly A.; Giovannucci, Edward] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Vajdic, Claire M.] Univ New S Wales, Prince Wales Clin Sch, Sydney, NSW 2052, Australia.
[Foo, Jia-Nee; Liu, Jianjun] Genome Inst Singapore, Singapore 138672, Singapore.
[Bracci, Paige M.; Holly, Elizabeth A.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94118 USA.
[Vermeulen, Roel C. H.] Univ Utrecht, Inst Risk Assessment Sci, NL-3508 TD Utrecht, Netherlands.
[Slager, Susan L.; Nowakowski, Grzegorz S.; Cerhan, James R.] Mayo Clin, Dept Hlth Sci Res, Rochester, MN 55905 USA.
[de Sanjose, Silvia; Benavente, Yolanda] Inst Catala Oncol, Unit Infect & Canc UNIC, Canc Epidemiol Res Programme, IDIBELL, Barcelona 8907, Spain.
[de Sanjose, Silvia; Benavente, Yolanda] CIBERESP, Barcelona 8036, Spain.
[Wang, Sophia S.] City Hope Beckman Res Inst, Dept Canc Etiol, Duarte, CA 91030 USA.
[Salles, Gilles] Hosp Civils Lyon, Dept Hematol, F-69495 Pierre Benite, France.
[Salles, Gilles] Univ Lyon 1, Dept Hematol, F-69495 Pierre Benite, France.
[Salles, Gilles; Ghesquieres, Herve] CNRS, UMR 5239, Lab Biol Mol Cellule, F-69495 Pierre Benite, France.
[Severi, Gianluca; Vineis, Paolo] Human Genet Fdn, I-10126 Turin, Italy.
[Severi, Gianluca; Giles, Graham G.] Canc Council Victoria, Canc Epidemiol Ctr, Melbourne, Vic 3053, Australia.
[Severi, Gianluca; Giles, Graham G.] Univ Melbourne, Melbourne Sch Populat & Global Hlth, Ctr Epidemiol & Biostat, Carlton, Vic 3010, Australia.
[Hjalgrim, Henrik; Melbye, Mads] Statens Serum Inst, Div Hlth Surveillance & Res, Dept Epidemiol Res, DK-2300 Copenhagen, Denmark.
[Lightfoot, Tracy; Smith, Alex; Roman, Eve; Kane, Eleanor] Univ York, Dept Hlth Sci, York YO10 5DD, N Yorkshire, England.
[Melbye, Mads] Stanford Univ, Dept Med, Sch Med, Stanford, CA 94305 USA.
[Gu, Jian; Ye, Yuanqing; Wu, Xifeng] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA.
[Ghesquieres, Herve] Ctr Leon Berard, Dept Hematol, F-69008 Lyon, France.
[Link, Brian K.; Weiner, George J.] Univ Iowa, Carver Coll Med, Dept Internal Med, Iowa City, IA 52242 USA.
[Tinker, Lesley F.; De Roos, Anneclaire J.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98117 USA.
[Teras, Lauren R.; Diver, W. Ryan] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30303 USA.
[Kricker, Anne; Armstrong, Bruce K.] Univ Sydney, Sydney Sch Publ Hlth, Sydney, NSW 2006, Australia.
[Becker, Nikolaus; Kaaks, Rudolph] German Canc Res Ctr, Div Canc Epidemiol, D-69120 Heidelberg, Baden Wurttembe, Germany.
[Spinelli, John J.] British Columbia Canc Agcy, Canc Control Res, Vancouver, BC V5Z 1L3, Canada.
[Spinelli, John J.] Univ British Columbia, Sch Populat & Publ Hlth, Vancouver, BC V6T 1Z3, Canada.
[Zhang, Yawei; Zheng, Tongzhang] Yale Univ, Sch Publ Hlth, Dept Environm Hlth Sci, New Haven, CT 06520 USA.
[Vineis, Paolo; Kelly, Rachel S.] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, MRC PHE Ctr Environm & Hlth, London W2 1PG, England.
[Monnereau, Alain; Clave, Jacqueline] INSERM, Ctr Res Epidemiol & Populat Hlth CESP, U1018, Environm Epidemiol Canc Grp, F-94807 Villejuif, France.
[Monnereau, Alain; Clave, Jacqueline] Univ Paris Sud, UMRS 1018, F-94807 Villejuif, France.
[Monnereau, Alain] Inst Bergonie, Registre Hemopathies Malignes Gironde, F-33076 Bordeaux, France.
[Bertrand, Kimberly A.; Liang, Liming; Huang, Jinyan; Ma, Baoshan; Adami, Hans-Olov; Kelly, Rachel S.; Giovannucci, Edward; Kraft, Peter] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Zeleniuch-Jacquotte, Anne] NYU, Sch Med, Dept Populat Hlth, New York, NY 10016 USA.
[Zeleniuch-Jacquotte, Anne] NYU, Inst Canc, Sch Med, New York, NY 10016 USA.
[Gabbas, Attilio; Ma, Baoshan; Cocco, Pierluigi] Univ Cagliari, Dept Publ Hlth Clin & Mol Med, I-09042 Cagliari, Italy.
[Lawrence, Charles; Montalvan, Rebecca] Westat Corp, Health Studies Sect, Rockville, MD 20850 USA.
[Liang, Liming; Kraft, Peter] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
Dalian Maritime Univ, Coll Informat Sci & Technol, Dalian 116026, Liaoning, Peoples R China.
[Adami, Hans-Olov; Weiderpass, Elisabete] Karolinska Inst, Dept Med Epidemiol & Biostat, S-17177 Stockholm, Sweden.
[Glimelius, Bengt] Karolinska Univ Hosp Solna, Karolinska Inst, Dept Oncol & Pathol, S-17176 Stockholm, Sweden.
[Glimelius, Bengt] Uppsala Univ, Dept Radiol Oncol & Radiat Sci, S-75105 Uppsala, Sweden.
[Dogan, Ahmet] Mem Sloan Kettering Canc Ctr, Dept Lab Med, New York, NY 10065 USA.
[Dogan, Ahmet] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10065 USA.
[Thompson, Carrie A.; Habermann, Thomas M.; Novak, Anne J.; Liebow, Mark; Witzig, Thomas E.] Mayo Clin, Dept Med, Rochester, MN 55905 USA.
[Schenk, Maryjean] Wayne State Univ, Dept Family Med & Publ Hlth Sci, Detroit, MI 48201 USA.
[De Roos, Anneclaire J.] Drexel Univ, Dept Environm & Occupat Hlth, Sch Publ Hlth, Philadelphia, PA 19104 USA.
[Cozen, Wendy] Univ So Calif, USC Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA.
[Cozen, Wendy] Univ So Calif, USC Keck Sch Med, Norris Comprehens Canc Ctr, Los Angeles, CA 90033 USA.
[Zhi, Degui] Univ Alabama Birmingham, Dept Biostat, Birmingham, AL 35233 USA.
[Jackson, Rebecca D.] Ohio State Univ, Div Endocrinol Diabet & Metab, Columbus, OH 43210 USA.
[North, Kari E.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27599 USA.
[North, Kari E.] Univ N Carolina, Carolina Ctr Genome Sci, Chapel Hill, NC 27599 USA.
[Turner, Jenny] Macquarie Univ, Australian Sch Adv Med, Dept Anat Pathol, Sydney, NSW 2109, Australia.
[Turner, Jenny] Douglass Hanly Moir Pathol, Dept Histopathol, Macquarie Pk, NSW 2113, Australia.
[Boffetta, Paolo] Icahn Sch Med Mt Sinai, Tisch Canc Inst, New York, NY 10029 USA.
[Brennan, Paul] Int Agcy Res Canc, Genet Sect, Grp Genet Epidemiol, F-69372 Lyon, France.
[Foretova, Lenka] Masaryk Mem Canc Inst, Dept Canc Epidemiol & Genet, Brno 65653, Czech Republic.
[Foretova, Lenka] MF MU, Brno 65653, Czech Republic.
[Maynadie, Marc] Univ Burgundy, EA 4184, Registre Hemopathies Malignes Cote Or, F-21070 Dijon, France.
[Maynadie, Marc] Dijon Univ Hosp, F-21070 Dijon, France.
[Staines, Anthony] Dublin City Univ, Sch Nursing & Human Sci, Dublin 9, Ireland.
[McKay, James] Int Agcy Res Canc, Genet Sect, Genet Canc Susceptibil Grp, F-69372 Lyon, France.
[Brooks-Wilson, Angela R.] British Columbia Canc Agcy, Genome Sci Ctr, Vancouver, BC V5Z 1L3, Canada.
[Brooks-Wilson, Angela R.] Simon Fraser Univ, Dept Biomed Physiol & Kinesiol, Burnaby, BC V5A 1S6, Canada.
[Holford, Theodore R.] Yale Univ, Sch Publ Hlth, Dept Biostat, New Haven, CT 06520 USA.
[Chamosa, Saioa] BioDonostia Res Inst, Dept Hlth, Basque Region 20014, Spain.
[Ohlsson, Bodil] Lund Univ, Skane Univ Hosp, Div Internal Med, Dept Clin Sci, S-20502 Malmo, Sweden.
[Travis, Ruth C.] Univ Oxford, Canc Epidemiol Unit, Oxford OX3 7LF, England.
[Weiderpass, Elisabete] Univ Tromso, Dept Community Med, Fac Hlth Sci, N-9037 Breivika, Norway.
[Weiderpass, Elisabete] Canc Registry Norway, N-0304 Oslo, Norway.
[Weiderpass, Elisabete] Folkhalsan Res Ctr, Dept Genet Epidemiol, Helsinki 00250, Finland.
[Giovannucci, Edward] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
[Virtamo, Jarmo] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki 00271, Finland.
[Mazza, Patrizio] Osped Nord, Dept Hematol, I-74100 Taranto, Italy.
[Ennas, Maria Grazia] Univ Cagliari, Dept Biomed Sci, I-09042 Cagliari, Italy.
[Chiu, Brian C. H.] Univ Chicago, Dept Hlth Studies, Chicago, IL 60637 USA.
[Nieters, Alexandra] Univ Med Ctr Freiburg, Ctr Chron Immunodeficiency, D-79108 Freiburg, Baden Wurttembe, Germany.
[Smedby, Karin E.] Karolinska Inst, Dept Med Solna, S-17176 Stockholm, Sweden.
RP Skibola, CF (reprint author), Sch Publ Hlth, Dept Epidemiol, Birmingham, AL 35233 USA.
EM cskibola@uab.edu
RI de Sanjose Llongueras, Silvia/H-6339-2014; Foo, Jia Nee/D-6069-2014;
Weiderpass, Elisabete/M-4029-2016; Clavel, Jacqueline/Q-2750-2016;
Vermeulen, Roel/F-8037-2011; Monnereau, Alain/L-1249-2014; de Bakker,
Paul/B-8730-2009; Morton, Lindsay/B-5234-2015; Albanes,
Demetrius/B-9749-2015; Brooks-Wilson, Angela/E-9399-2012; Armstrong,
Bruce/K-9464-2015; Conde, Lucia/D-9295-2011; Purdue, Mark/C-9228-2016;
OI Foo, Jia Nee/0000-0001-9899-2308; Weiderpass,
Elisabete/0000-0003-2237-0128; Clavel, Jacqueline/0000-0002-3616-7676;
Vermeulen, Roel/0000-0003-4082-8163; Monnereau,
Alain/0000-0002-5056-1397; de Bakker, Paul/0000-0001-7735-7858; Morton,
Lindsay/0000-0001-9767-2310; Brooks-Wilson, Angela/0000-0003-1009-6408;
Armstrong, Bruce/0000-0001-8940-7525; Purdue, Mark/0000-0003-1177-3108;
Chamosa, Saioa/0000-0002-8321-4404; Ennas, Maria
Grazia/0000-0002-9448-715X; Staines, Anthony/0000-0001-9161-1357;
Salles, Gilles/0000-0002-9541-8666; Joseph, Vijai/0000-0002-7933-151X;
Giles, Graham/0000-0003-4946-9099; Zeleniuch-Jacquotte,
Anne/0000-0001-9350-1303
FU Division of Cancer Epidemiology and Genetics, National Cancer Institute,
NIH
FX The overall FL GWAS project was supported by the intramural program of
the Division of Cancer Epidemiology and Genetics, National Cancer
Institute, NIH. A full list of Supplemental Acknowledgements is provided
online.
NR 25
TC 19
Z9 19
U1 3
U2 24
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 OCT 2
PY 2014
VL 95
IS 4
BP 462
EP 471
DI 10.1016/j.ajhg.2014.09.004
PG 10
WC Genetics & Heredity
SC Genetics & Heredity
GA AQ2XW
UT WOS:000342654300011
PM 25279986
ER
PT J
AU Yeung, J
Tourdot, BE
Fernandez-Perez, P
Vesci, J
Ren, J
Smyrniotis, CJ
Luci, DK
Jadhav, A
Simeonov, A
Maloney, DJ
Holman, TR
McKenzie, SE
Holinstat, M
AF Yeung, Jennifer
Tourdot, Benjamin E.
Fernandez-Perez, Pilar
Vesci, Joanne
Ren, Jin
Smyrniotis, Christopher J.
Luci, Diane K.
Jadhav, Ajit
Simeonov, Anton
Maloney, David J.
Holman, Theodore R.
McKenzie, Steven E.
Holinstat, Michael
TI Platelet 12-LOX is essential for Fc gamma RIIa-mediated platelet
activation
SO BLOOD
LA English
DT Article
ID PROTEIN-KINASE-C; STIMULATES TYROSINE PHOSPHORYLATION; HEPARIN-INDUCED
THROMBOCYTOPENIA; PROSTATE-CANCER CELLS; GLYCOPROTEIN-VI; THROMBUS
FORMATION; INTEGRIN ALPHA-IIB-BETA-3; IMMUNOGLOBULIN-G; RECEPTOR CLEC-2;
12-LIPOXYGENASE
AB Platelets are essential in maintaining hemostasis following inflammation or injury to the vasculature. Dysregulated platelet activity often results in thrombotic complications leading to myocardial infarction and stroke. Activation of the Fc gamma RIIa receptor leads to immune-mediated thrombosis, which is often life threatening in patients undergoing heparin-induced thrombocytopenia or sepsis. Inhibiting Fc gamma RIIa-mediated activation in platelets has been shown to limit thrombosis and is the principal target for prevention of immune-mediated platelet activation. In this study, we show for the first time that platelet 12(S)-lipoxygenase (12-LOX), a highly expressed oxylipin-producing enzyme in the human platelet, is an essential component of Fc gamma RIIa-mediated thrombosis. Pharmacologic inhibition of 12-LOX in human platelets resulted in significant attenuation of Fc gamma RIIa-mediated aggregation. Platelet 12-LOX was shown to be essential for Fc gamma RIIa-induced phospholipase C gamma 2 activity leading to activation of calcium mobilization, Rap1 and protein kinase C activation, and subsequent activation of the integrin alpha IIb beta 3. Additionally, platelets from transgenic mice expressing human Fc gamma RIIa but deficient in platelet 12-LOX, failed to form normal platelet aggregates and exhibited deficiencies in Rap1 and alpha IIb beta 3 activation. These results support an essential role for 12-LOX in regulating Fc gamma RIIa-mediated platelet function and identifies 12-LOX as a potential therapeutic target to limit immune-mediated thrombosis.
C1 [Yeung, Jennifer; Tourdot, Benjamin E.; Fernandez-Perez, Pilar; Vesci, Joanne; Ren, Jin; McKenzie, Steven E.; Holinstat, Michael] Thomas Jefferson Univ, Dept Med, Cardeza Fdn Hematol Res, Philadelphia, PA 19107 USA.
[Smyrniotis, Christopher J.; Holman, Theodore R.] Univ Calif Santa Cruz, Dept Chem & Biochem, Santa Cruz, CA 95064 USA.
[Luci, Diane K.; Jadhav, Ajit; Simeonov, Anton; Maloney, David J.] NIH, Chem Genom Ctr, Natl Ctr Advancing Translat Sci, Rockville, MD USA.
RP Holinstat, M (reprint author), Thomas Jefferson Univ, Dept Med, Cardeza Fdn Hematol Res, 1020 Locust St,Suite 394,Jefferson Alumni Hall, Philadelphia, PA 19107 USA.
EM michael.holinstat@jefferson.edu
FU National Institutes of Health (National Institute of General Medical
Sciences) [R01 GM105671]; National Institutes of Health (National Heart,
Lung, and Blood Institute) [R01 HL114405]; National Institutes of Health
(National Institute on Minority Health and Health Disparities) [R01
MD007880]; American Heart Association [12BGIA11890000]; Parenteral Drug
Association Foundation for Pharmaceutical Sciences; National Heart,
Lung, and Blood Institute [P01 HL110860]; Cardeza Foundation for
Hematologic Research; National Center for Advancing Translational
Sciences; Molecular Libraries Initiative of the National Institutes of
Health Roadmap for Medical Research [U54MH084681]
FX This study was supported in part by grants from the National Institutes
of Health (National Institute of General Medical Sciences; R01 GM105671)
(M. H.), (National Heart, Lung, and Blood Institute; R01 HL114405) (M.
H. and S. E. M.), and (National Institute on Minority Health and Health
Disparities; R01 MD007880) (M. H.), the American Heart Association
(12BGIA11890000) (M. H.), the Parenteral Drug Association Foundation for
Pharmaceutical Sciences (M. H.), National Heart, Lung, and Blood
Institute; (P01 HL110860) (S. E. M.), and the Cardeza Foundation for
Hematologic Research (M. H. and S. E. M.). D. K. L., A.J., A. S., and
D.J.M. were supported by the intramural research program of the National
Center for Advancing Translational Sciences and the Molecular Libraries
Initiative of the National Institutes of Health Roadmap for Medical
Research (U54MH084681).
NR 54
TC 11
Z9 11
U1 0
U2 9
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA
SN 0006-4971
EI 1528-0020
J9 BLOOD
JI Blood
PD OCT 2
PY 2014
VL 124
IS 14
BP 2271
EP 2279
DI 10.1182/blood-2014-05-575878
PG 9
WC Hematology
SC Hematology
GA AQ4KC
UT WOS:000342763900020
PM 25100742
ER
PT J
AU Morrison, AC
Bis, JC
Hwang, SJ
Ehret, GB
Lumley, T
Rice, K
Muzny, D
Gibbs, RA
Boerwinkle, E
Psaty, BM
Chakravarti, A
Levy, D
AF Morrison, Alanna C.
Bis, Joshua C.
Hwang, Shih-Jen
Ehret, Georg B.
Lumley, Thomas
Rice, Kenneth
Muzny, Donna
Gibbs, Richard A.
Boerwinkle, Eric
Psaty, Bruce M.
Chakravarti, Aravinda
Levy, Daniel
TI Sequence Analysis of Six Blood Pressure Candidate Regions in 4,178
Individuals: The Cohorts for Heart and Aging Research in Genomic
Epidemiology (CHARGE) Targeted Sequencing Study
SO PLOS ONE
LA English
DT Article
ID WIDE ASSOCIATION; DESIGN; HYPERTENSION; RISK
AB Background: Genome-wide association studies (GWAS) identified multiple loci for blood pressure (BP) and hypertension. Six genes - ATP2B1, CACNB2, CYP17A1, JAG1, PLEKHA7, and SH2B3 - were evaluated for sequence variation with large effects on systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse pressure (PP), and mean arterial pressure (MAP).
Methods and Results: Targeted genomic sequence was determined in 4,178 European ancestry participants from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium. Common variants (>= 50 minor allele copies) were evaluated individually and rare variants (minor allele frequency, MAF <= 1%) were aggregated by locus. 464 common variants were identified across the 6 genes. An upstream CYP17A1 variant, rs11191416 (MAF = 0.09), was the most significant association for SBP (P = 0.0005); however the association was attenuated (P = 0.0469) after conditioning on the GWAS index single nucleotide polymorphism (SNP). A PLEKHA7 intronic variant was the strongest DBP association (rs12806040, MAF = 0.007, P = 0.0006) and was not in LD (r(2) = 0.01) with the GWAS SNP. A CACNB2 intronic SNP, rs1571787, was the most significant association with PP (MAF = 0.27, P = 0.0003), but was not independent from the GWAS SNP (r(2) = 0.34). Three variants (rs6163 and rs743572 in the CYP17A1 region and rs112467382 in PLEKHA7) were associated with BP traits (P<0.001). Rare variation, aggregately assessed in the 6 regions, was not significantly associated with BP measures.
Conclusion: Six targeted gene regions, previously identified by GWAS, did not harbor novel variation with large effects on BP in this sample.
C1 [Morrison, Alanna C.; Boerwinkle, Eric] Univ Texas Hlth Sci Ctr Houston, Houston, TX 77030 USA.
[Bis, Joshua C.; Rice, Kenneth; Psaty, Bruce M.] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA.
[Psaty, Bruce M.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
[Psaty, Bruce M.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA.
[Hwang, Shih-Jen; Levy, Daniel] Framingham Heart Dis Epidemiol Study, Framingham, MA USA.
[Hwang, Shih-Jen; Levy, Daniel] NHLBI, Populat Sci Branch, NIH, Bethesda, MD 20892 USA.
[Ehret, Georg B.] Univ Hosp Geneva, Dept Med Specialties, Geneva, Switzerland.
[Lumley, Thomas] Univ Auckland, Dept Stat, Auckland 1, New Zealand.
[Ehret, Georg B.; Chakravarti, Aravinda] Johns Hopkins Univ, Sch Med, Inst Med Genet, Ctr Complex Dis Genom, Baltimore, MD USA.
[Muzny, Donna; Gibbs, Richard A.; Boerwinkle, Eric] Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA.
[Psaty, Bruce M.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA USA.
RP Morrison, AC (reprint author), Univ Texas Hlth Sci Ctr Houston, Houston, TX 77030 USA.
EM Alanna.C.Morrison@uth.tmc.edu
RI EHRET, Georg/A-9532-2009
OI EHRET, Georg/0000-0002-5730-0675
FU National Institutes of Health (NIH) through the American Recovery and
Reinvestment Act (ARRA) [5RC2HL102419]; National Heart, Lung, and Blood
Institute (NHLBI) [HHSN268201100005C, HHSN268201100006C,
HHSN268201100007C, HHSN268201100008C, HHSN268201100009C,
HHSN268201100010C, HHSN268201100011C, HHSN268201100012C]; NHLBI
[HL080295, HL087652, HL105756]; Boston University [N01-HC-25195]; Robert
Dawson Evans Endowment of the Department of Medicine at Boston
University School of Medicine; Boston Medical Center; NIA [AG-023629,
AG-15928, AG-20098, AG-027058]; [U54 HG003273]
FX Funding support for "Building on GWAS for NHLBI-diseases: the U.S.
CHARGE Consortium'' was provided by the National Institutes of Health
(NIH) through the American Recovery and Reinvestment Act of 2009 (ARRA)
(5RC2HL102419). The Human Genome Sequencing Center at Baylor College of
Medicine is supported by U54 HG003273. Data for "Building on GWAS for
NHLBI-diseases: the U.S. CHARGE Consortium'' was provided by Eric
Boerwinkle on behalf of the Atherosclerosis Risk in Communities (ARIC)
Study, L. Adrienne Cupples, principal investigator for the Framingham
Heart Study, and Bruce Psaty, principal investigator for the
Cardiovascular Health Study. The ARIC Study is carried out as a
collaborative study supported by National Heart, Lung, and Blood
Institute (NHLBI) contracts (HHSN268201100005C, HHSN268201100006C,
HHSN268201100007C, HHSN268201100008C, HHSN268201100009C,
HHSN268201100010C, HHSN268201100011C, and HHSN268201100012C). The
Framingham Heart Study is conducted and supported by the NHLBI in
collaboration with Boston University (Contract No. N01-HC-25195), and
its contract with Affymetrix, Inc., for genome-wide genotyping services
(Contract No. N02-HL-6-4278), for quality control by Framingham Heart
Study investigators using genotypes in the SNP Health Association
Resource (SHARe) project. A portion of this research was conducted using
the Linux Cluster for Genetic Analysis (LinGA-II) funded by the Robert
Dawson Evans Endowment of the Department of Medicine at Boston
University School of Medicine and Boston Medical Center. This 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, HHSN268201200036C and NHLBI grants
HL080295, HL087652, HL105756, 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 funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 17
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U1 1
U2 5
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD OCT 2
PY 2014
VL 9
IS 10
AR e109155
DI 10.1371/journal.pone.0109155
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AQ2BX
UT WOS:000342591500069
PM 25275628
ER
PT J
AU Watts, SD
Torres-Salazar, D
Divito, CB
Amara, SG
AF Watts, Spencer D.
Torres-Salazar, Delany
Divito, Christopher B.
Amara, Susan G.
TI Cysteine Transport through Excitatory Amino Acid Transporter 3 (EAAT3)
SO PLOS ONE
LA English
DT Article
ID NEURONAL GLUTAMATE TRANSPORTER; SUBSTRATE TRANSPORT; ANION CONDUCTANCE;
MEDIATED RELEASE; HIGH-AFFINITY; CARRIER 1; FAMILY; EAAC1;
NEUROTRANSMITTERS; SELENOCYSTEINE
AB Excitatory amino acid transporters (EAATs) limit glutamatergic signaling and maintain extracellular glutamate concentrations below neurotoxic levels. Of the five known EAAT isoforms (EAATs 1-5), only the neuronal isoform, EAAT3 (EAAC1), can efficiently transport the uncharged amino acid L-cysteine. EAAT3-mediated cysteine transport has been proposed to be a primary mechanism used by neurons to obtain cysteine for the synthesis of glutathione, a key molecule in preventing oxidative stress and neuronal toxicity. The molecular mechanisms underlying the selective transport of cysteine by EAAT3 have not been elucidated. Here we propose that the transport of cysteine through EAAT3 requires formation of the thiolate form of cysteine in the binding site. Using Xenopus oocytes and HEK293 cells expressing EAAT2 and EAAT3, we assessed the transport kinetics of different substrates and measured transporter-associated currents electrophysiologically. Our results show that L-selenocysteine, a cysteine analog that forms a negatively-charged selenolate ion at physiological pH, is efficiently transported by EAATs 1-3 and has a much higher apparent affinity for transport when compared to cysteine. Using a membrane tethered GFP variant to monitor intracellular pH changes associated with transport activity, we observed that transport of either L-glutamate or L-selenocysteine by EAAT3 decreased intracellular pH, whereas transport of cysteine resulted in cytoplasmic alkalinization. No change in pH was observed when cysteine was applied to cells expressing EAAT2, which displays negligible transport of cysteine. Under conditions that favor release of intracellular substrates through EAAT3 we observed release of labeled intracellular glutamate but did not detect cysteine release. Our results support a model whereby cysteine transport through EAAT3 is facilitated through cysteine de-protonation and that once inside, the thiolate is rapidly re-protonated. Moreover, these findings suggest that cysteine transport is predominantly unidirectional and that reverse transport does not contribute to depletion of intracellular cysteine pools.
C1 [Watts, Spencer D.; Divito, Christopher B.; Amara, Susan G.] Univ Pittsburgh, Ctr Neurosci, Dept Neurobiol, Pittsburgh, PA 15260 USA.
[Torres-Salazar, Delany; Amara, Susan G.] NIMH, Lab Cellular & Mol Neurobiol, NIH, Bethesda, MD 20892 USA.
RP Amara, SG (reprint author), Univ Pittsburgh, Ctr Neurosci, Dept Neurobiol, Pittsburgh, PA 15260 USA.
EM susan.amara@nih.gov
FU National Institutes of Health [MH080726]; American Heart Association
postdoctoral fellowship [09POST2010115]
FX The work was supported by National Institutes of Health Grant MH080726
to SGA and the American Heart Association postdoctoral fellowship
(#09POST2010115) to DT-S. The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 40
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U1 3
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 OCT 2
PY 2014
VL 9
IS 10
AR e109245
DI 10.1371/journal.pone.0109245
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AQ2BX
UT WOS:000342591500082
PM 25275463
ER
PT J
AU Oh, J
Byrd, AL
Deming, C
Conlan, S
Kong, HH
Segre, JA
AF Oh, Julia
Byrd, Allyson L.
Deming, Clay
Conlan, Sean
Kong, Heidi H.
Segre, Julia A.
CA NISC Comparative Sequencing Progra
TI Biogeography and individuality shape function in the human skin
metagenome
SO NATURE
LA English
DT Article
ID MAXIMUM-LIKELIHOOD; MICROBIOME; DIVERSITY; GENES; IDENTIFICATION;
ALGORITHMS; SEQUENCES; ALIGNMENT; VIROME; GENOME
AB The varied topography of human skin offers a unique opportunity to study how the body's microenvironments influence the functional and taxonomic composition of microbial communities. Phylogenetic marker gene-based studies have identified many bacteria and fungi that colonize distinct skin niches. Here metagenomic analyses of diverse body sites in healthy humans demonstrate that local biogeography and strong individuality define the skin microbiome. We developed a relational analysis of bacterial, fungal and viral communities, which showed not only site specificity but also individual signatures. We further identified strain-level variation of dominant species as heterogeneous and multiphyletic. Reference-free analyses captured the uncharacterized metagenome through the development of a multi-kingdom gene catalogue, which was used to uncover genetic signatures of species lacking reference genomes. This work is foundational for human disease studies investigating inter-kingdom interactions, metabolic changes and strain tracking, and defines the dual influence of biogeography and individuality on microbial composition and function.
C1 [Oh, Julia; Byrd, Allyson L.; Deming, Clay; Conlan, Sean; Segre, Julia A.] NHGRI, Translat & Funct Genom Branch, NIH, Bethesda, MD 20892 USA.
[Kong, Heidi H.] NCI, Dermatol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Kong, HH (reprint author), NCI, Dermatol Branch, Ctr Canc Res, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM konghe@mail.nih.gov; jsegre@mail.nih.gov
OI Kong, Heidi/0000-0003-4424-064X
FU National Institutes of Health (NIH) NHGRI; National Institutes of Health
(NIH) NCI; National Institutes of Health [1UH2AR057504-01,
4UH3AR057504-02]; [1K99AR059222]
FX We thank D. Schoenfeld, A. Pradhan, M. Park and G. Bouffard for their
efforts. We also thank members of the Segre laboratory and M. C. Udey
for their discussions. This work was supported by National Institutes of
Health (NIH) NHGRI and NCI Intramural Research Programs and in part by
1K99AR059222 (H. H. K.). This study used the high-performance
computational capabilities of the NIH Biowulf Linux cluster. Sequencing
was funded by grants from the National Institutes of Health
(1UH2AR057504-01 and 4UH3AR057504-02).
NR 40
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U1 14
U2 126
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 OCT 2
PY 2014
VL 514
IS 7520
BP 59
EP +
DI 10.1038/nature13786
PG 19
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AP9SS
UT WOS:000342420800034
PM 25279917
ER
PT J
AU Perry, JRB
Day, F
Elks, CE
Sulem, P
Thompson, DJ
Ferreira, T
He, CY
Chasman, DI
Esko, T
Thorleifsson, G
Albrecht, E
Ang, WQ
Corre, T
Cousminer, DL
Feenstra, B
Franceschini, N
Ganna, A
Johnson, AD
Kjellqvist, S
Lunetta, KL
McMahon, G
Nolte, IM
Paternoster, L
Porcu, E
Smith, AV
Stolk, L
Teumer, A
Tsernikova, N
Tikkanen, E
Ulivi, S
Wagner, EK
Amin, N
Bierut, LJ
Byrne, EM
Hottenga, JJ
Koller, DL
Mangino, M
Pers, TH
Yerges-Armstrong, LM
Zhao, JH
Andrulis, IL
Anton-Culver, H
Atsma, F
Bandinelli, S
Beckmann, MW
Benitez, J
Blomqvist, C
Bojesen, SE
Bolla, MK
Bonanni, B
Brauch, H
Brenner, H
Buring, JE
Chang-Claude, J
Chanock, S
Chen, JH
Chenevix-Trench, G
Collee, JM
Couch, FJ
Couper, D
Coviello, AD
Cox, A
Czene, K
D'adamo, AP
Smith, GD
De Vivo, I
Demerath, EW
Dennis, J
Devilee, P
Dieffenbach, AK
Dunning, AM
Eiriksdottir, G
Eriksson, JG
Fasching, PA
Ferrucci, L
Flesch-Janys, D
Flyger, H
Foroud, T
Franke, L
Garcia, ME
Garcia-Closas, M
Geller, F
de Geus, EEJ
Giles, GG
Gudbjartsson, DF
Gudnason, V
Guenel, P
Guo, SQ
Hall, P
Hamann, U
Haring, R
Hartman, CA
Heath, A
Hofman, A
Hooning, MJ
Hopper, JL
Hu, FB
Hunter, DJ
Karasik, D
Kiel, DP
Knight, JA
Kosma, VM
Kutalik, Z
Lai, S
Lambrechts, D
Lindblom, A
Magi, R
Magnusson, PK
Mannermaa, A
Martin, NG
Masson, G
McArdle, PF
McArdle, WL
Melbye, M
Michailidou, K
Mihailov, E
Milani, L
Milne, RL
Nevanlinna, H
Neven, P
Nohr, EA
Oldehinkel, AJ
Oostra, BA
Palotie, A
Peacock, M
Pedersen, NL
Peterlongo, P
Peto, J
Pharoah, PDP
Postma, DS
Pouta, A
Pylkas, K
Radice, P
Ring, S
Rivadeneira, F
Robino, A
Rose, LM
Rudolph, A
Salomaa, V
Sanna, S
Schlessinger, D
Schmidt, MK
Southey, MC
Sovio, U
Stampfer, MJ
Stockl, D
Storniolo, AM
Timpson, NJ
Tyrer, J
Visser, JA
Vollenweider, P
Volzke, H
Waeber, G
Waldenberger, M
Wallaschofski, H
Wang, Q
Willemsen, G
Winqvist, R
Wolffenbuttel, BHR
Wright, MJ
Boomsma, DI
Econs, MJ
Khaw, KT
Loos, RJF
McCarthy, MI
Montgomery, GW
Rice, JP
Streeten, EA
Thorsteinsdottir, U
van Duijn, CM
Alizadeh, BZ
Bergmann, S
Boerwinkle, E
Boyd, HA
Crisponi, L
Gasparini, P
Gieger, C
Harris, TB
Ingelsson, E
Jarvelin, MR
Kraft, P
Lawlor, D
Metspalu, A
Pennell, CE
Ridker, PM
Snieder, H
Sorensen, TIA
Spector, TD
Strachan, DP
Uitterlinden, AG
Wareham, NJ
Widen, E
Zygmunt, M
Murray, A
Easton, DF
Stefansson, K
Murabito, JM
Ong, KK
AF Perry, John R. B.
Day, Felix
Elks, Cathy E.
Sulem, Patrick
Thompson, Deborah J.
Ferreira, Teresa
He, Chunyan
Chasman, Daniel I.
Esko, Toenu
Thorleifsson, Gudmar
Albrecht, Eva
Ang, Wei Q.
Corre, Tanguy
Cousminer, Diana L.
Feenstra, Bjarke
Franceschini, Nora
Ganna, Andrea
Johnson, Andrew D.
Kjellqvist, Sanela
Lunetta, Kathryn L.
McMahon, George
Nolte, Ilja M.
Paternoster, Lavinia
Porcu, Eleonora
Smith, Albert V.
Stolk, Lisette
Teumer, Alexander
Tsernikova, Natalia
Tikkanen, Emmi
Ulivi, Sheila
Wagner, Erin K.
Amin, Najaf
Bierut, Laura J.
Byrne, Enda M.
Hottenga, Jouke-Jan
Koller, Daniel L.
Mangino, Massimo
Pers, Tune H.
Yerges-Armstrong, Laura M.
Zhao, Jing Hua
Andrulis, Irene L.
Anton-Culver, Hoda
Atsma, Femke
Bandinelli, Stefania
Beckmann, Matthias W.
Benitez, Javier
Blomqvist, Carl
Bojesen, Stig E.
Bolla, Manjeet K.
Bonanni, Bernardo
Brauch, Hiltrud
Brenner, Hermann
Buring, Julie E.
Chang-Claude, Jenny
Chanock, Stephen
Chen, Jinhui
Chenevix-Trench, Georgia
Collee, J. Margriet
Couch, Fergus J.
Couper, David
Coviello, Andrea D.
Cox, Angela
Czene, Kamila
D'adamo, Adamo Pio
Smith, George Davey
De Vivo, Immaculata
Demerath, Ellen W.
Dennis, Joe
Devilee, Peter
Dieffenbach, Aida K.
Dunning, Alison M.
Eiriksdottir, Gudny
Eriksson, Johan G.
Fasching, Peter A.
Ferrucci, Luigi
Flesch-Janys, Dieter
Flyger, Henrik
Foroud, Tatiana
Franke, Lude
Garcia, Melissa E.
Garcia-Closas, Montserrat
Geller, Frank
de Geus, Eco E. J.
Giles, Graham G.
Gudbjartsson, Daniel F.
Gudnason, Vilmundur
Guenel, Pascal
Guo, Suiqun
Hall, Per
Hamann, Ute
Haring, Robin
Hartman, Catharina A.
Heath, AndrewC.
Hofman, Albert
Hooning, Maartje J.
Hopper, John L.
Hu, Frank B.
Hunter, David J.
Karasik, David
Kiel, Douglas P.
Knight, Julia A.
Kosma, Veli-Matti
Kutalik, Zoltan
Lai, Sandra
Lambrechts, Diether
Lindblom, Annika
Maegi, Reedik
Magnusson, Patrik K.
Mannermaa, Arto
Martin, Nicholas G.
Masson, Gisli
McArdle, Patrick F.
McArdle, Wendy L.
Melbye, Mads
Michailidou, Kyriaki
Mihailov, Evelin
Milani, Lili
Milne, Roger L.
Nevanlinna, Heli
Neven, Patrick
Nohr, Ellen A.
Oldehinkel, Albertine J.
Oostra, Ben A.
Palotie, Aarno
Peacock, Munro
Pedersen, Nancy L.
Peterlongo, Paolo
Peto, Julian
Pharoah, Paul D. P.
Postma, Dirkje S.
Pouta, Anneli
Pylkaes, Katri
Radice, Paolo
Ring, Susan
Rivadeneira, Fernando
Robino, Antonietta
Rose, Lynda M.
Rudolph, Anja
Salomaa, Veikko
Sanna, Serena
Schlessinger, David
Schmidt, Marjanka K.
Southey, Mellissa C.
Sovio, Ulla
Stampfer, Meir J.
Stoeckl, Doris
Storniolo, Anna M.
Timpson, Nicholas J.
Tyrer, Jonathan
Visser, Jenny A.
Vollenweider, Peter
Voelzke, Henry
Waeber, Gerard
Waldenberger, Melanie
Wallaschofski, Henri
Wang, Qin
Willemsen, Gonneke
Winqvist, Robert
Wolffenbuttel, Bruce H. R.
Wright, Margaret J.
Boomsma, Dorret I.
Econs, Michael J.
Khaw, Kay-Tee
Loos, Ruth J. F.
McCarthy, Mark I.
Montgomery, Grant W.
Rice, John P.
Streeten, Elizabeth A.
Thorsteinsdottir, Unnur
van Duijn, Cornelia M.
Alizadeh, Behrooz Z.
Bergmann, Sven
Boerwinkle, Eric
Boyd, Heather A.
Crisponi, Laura
Gasparini, Paolo
Gieger, Christian
Harris, Tamara B.
Ingelsson, Erik
Jaervelin, Marjo-Riitta
Kraft, Peter
Lawlor, Debbie
Metspalu, Andres
Pennell, Craig E.
Ridker, Paul M.
Snieder, Harold
Sorensen, Thorkild I. A.
Spector, Tim D.
Strachan, David P.
Uitterlinden, Andre G.
Wareham, Nicholas J.
Widen, Elisabeth
Zygmunt, Marek
Murray, Anna
Easton, Douglas F.
Stefansson, Kari
Murabito, Joanne M.
Ong, Ken K.
CA Australian Ovarian Canc Study
GENICA Network
kConFabt LifeLines Cohort Study
InterAct Consortium
Early Growth Genetics EGG Consorti
TI Parent-of-origin-specific allelic associations among 106 genomic loci
for age at menarche
SO NATURE
LA English
DT Article
ID CENTRAL PRECOCIOUS PUBERTY; HUMAN PREFRONTAL CORTEX; BREAST-CANCER RISK;
GENE-EXPRESSION; WIDE ASSOCIATION; METAANALYSIS; DISEASE; VARIANTS;
CELLS; REVEALS
AB Age at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-causemortality(1). Studies of rare human disorders of puberty and animal models point to a complex hypothalamic-pituitary-hormonal regulation(2,3), but the mechanisms that determine pubertal timing and underlie its links to disease risk remain unclear. Here, using genome-wide and custom-genotyping arrays in up to 182,416 women of European descent from 57 studies, we found robust evidence (P < 5 x 10(-8)) for 123 signals at 106 genomic loci associated with age at menarche. Many loci were associated with other pubertal traits in both sexes, and there was substantial overlap with genes implicated in body mass index and various diseases, including rare disorders of puberty. Menarche signals were enriched in imprinted regions, with three loci (DLK1-WDR25, MKRN3-MAGEL2 and KCNK9) demonstrating parent-of-origin-specific associations concordant with known parental expression patterns. Pathway analyses implicated nuclear hormone receptors, particularly retinoic acid and gamma-aminobutyric acid-B2 receptor signalling, among novel mechanisms that regulate pubertal timing in humans. Our findings suggest a genetic architecture involving at least hundreds of common variants in the coordinated timing of the pubertal transition.
C1 [Perry, John R. B.; Day, Felix; Elks, Cathy E.; Zhao, Jing Hua; Loos, Ruth J. F.; Wareham, Nicholas J.; Ong, Ken K.] Univ Cambridge, Sch Clin Med, MRC Epidemiol Unit, Inst Metab Sci, Cambridge CB2 0QQ, England.
[Perry, John R. B.; Murray, Anna] Univ Exeter, Sch Med, Exeter EX1 2LU, Devon, England.
[Perry, John R. B.; Ferreira, Teresa; McCarthy, Mark I.] Univ Oxford, Wellcome Trust Ctr forHuman Genet, Oxford OX3 7BN, England.
[Perry, John R. B.; Mangino, Massimo; Spector, Tim D.] Kings Coll London, Dept Twin Res & Genet Epidemiol, London SE1 7EH, England.
[Sulem, Patrick; Thorleifsson, Gudmar; Masson, Gisli; Thorsteinsdottir, Unnur; Stefansson, Kari] DeCODE Genet, IS-101 Reykjavik, Iceland.
[Thompson, Deborah J.; Bolla, Manjeet K.; Dennis, Joe; Gudbjartsson, Daniel F.; Michailidou, Kyriaki; Wang, Qin; Easton, Douglas F.] Univ Cambridge, Dept Publ Hlth & Primary Care, Ctr Canc Genet Epidemiol, Cambridge CB1 8RN, England.
[He, Chunyan; Wagner, Erin K.] Indiana Univ, Richard M Fairbanks Sch Publ Hlth, Dept Epidemiol, Indianapolis, IN 46202 USA.
[He, Chunyan; Wagner, Erin K.] Indiana Univ, Melvin & Bren Simon Canc Ctr, Indianapolis, IN 46202 USA.
[Chasman, Daniel I.; Buring, Julie E.; Rose, Lynda M.; Ridker, Paul M.] Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02215 USA.
[Chasman, Daniel I.; Buring, Julie E.; Karasik, David; Ridker, Paul M.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Esko, Toenu; Tsernikova, Natalia; Maegi, Reedik; Mihailov, Evelin; Milani, Lili; Metspalu, Andres] Univ Tartu, Estonian Genome Ctr, Tartu 51010, Estonia.
[Esko, Toenu; Pers, Tune H.] Boston Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA.
[Esko, Toenu; Pers, Tune H.] Boston Childrens Hosp, Div Genet, Boston, MA 02115 USA.
[Esko, Toenu; Pers, Tune H.] Boston Childrens Hosp, Ctr Basic & Translat Obes Res, Boston, MA 02115 USA.
[Esko, Toenu; Pers, Tune H.; Hunter, David J.] MIT, Board Inst, Cambridge, MA 02142 USA.
[Esko, Toenu; Pers, Tune H.; Hunter, David J.] Harvard Univ, Cambridge, MA 02142 USA.
[Esko, Toenu] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
[Albrecht, Eva; Gieger, Christian] Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Genet Epidemiol, D-85764 Neuherberg, Germany.
[Ang, Wei Q.; Pennell, Craig E.] Univ Western Australia, Sch Womens & Infants Hlth, Nedlands, WA 6009, Australia.
[Corre, Tanguy; Kutalik, Zoltan; Bergmann, Sven] Univ Lausanne, Dept Med Genet, CH-1005 Lausanne, Switzerland.
[Corre, Tanguy; Kutalik, Zoltan; Bergmann, Sven] Swiss Inst Bioinformat, CH-1015 Lausanne, Switzerland.
[Cousminer, Diana L.; Tikkanen, Emmi; Palotie, Aarno; Widen, Elisabeth] Univ Helsinki, Inst Mol Med Finland FIMM, FI-00014 Helsinki, Finland.
[Feenstra, Bjarke; Geller, Frank; Melbye, Mads; Boyd, Heather A.] Statens Serum Inst, Dept Epidemiol Res, DK-2300 Copenhagen, Denmark.
[Franceschini, Nora] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27599 USA.
[Ganna, Andrea; Czene, Kamila; Hall, Per; Magnusson, Patrik K.; Pedersen, Nancy L.] Karolinska Inst, Dept Med Epidemiol & Biostat, S-17177 Stockholm, Sweden.
[Johnson, Andrew D.; Lunetta, Kathryn L.; Murabito, Joanne M.] NHLBI, Framingham, MA 01702 USA.
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[Kjellqvist, Sanela] Karolinska Inst, Sci Life Lab, S-17121 Solna, Sweden.
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[Porcu, Eleonora; Lai, Sandra; Sanna, Serena; Crisponi, Laura] CNR, Inst Genet & Biomed Res, I-09042 Cagliari, Sardinia, Italy.
[Porcu, Eleonora] Univ Sassari, Dept Biomed Sci, I-07100 Sassari, Italy.
[Smith, Albert V.; Eiriksdottir, Gudny; Gudnason, Vilmundur] Iceland Heart Assoc, IS-201 Kopavogur, Iceland.
[Smith, Albert V.; Gudnason, Vilmundur] Univ Iceland, IS-101 Reykjavik, Iceland.
[Stolk, Lisette; Rivadeneira, Fernando; Visser, Jenny A.; Uitterlinden, Andre G.] Erasmus MC, Dept Internal Med, NL-3015 GE Rotterdam, Netherlands.
[Stolk, Lisette; Rivadeneira, Fernando; van Duijn, Cornelia M.; Uitterlinden, Andre G.] Netherlands Consortium Hlth Aging, NL-2300 RC Leiden, Netherlands.
[Stolk, Lisette; Rivadeneira, Fernando; van Duijn, Cornelia M.; Uitterlinden, Andre G.] Natl Genom Initiat, NL-2300 RC Leiden, Netherlands.
[Teumer, Alexander] Univ Med Greifswald, Interfac Inst Genet & Funct Gen, D-17475 Greifswald, Germany.
[Tsernikova, Natalia; Mihailov, Evelin; Metspalu, Andres] Univ Tartu, Dept Biotechnol, EE-51010 Tartu, Estonia.
[Tikkanen, Emmi] Univ Helsinki, Hjelt Inst, FI-00014 Helsinki, Finland.
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[Amin, Najaf; Oostra, Ben A.; van Duijn, Cornelia M.] Eramus MC, Dept Epidemiol, Genet Epidemiol Unit, NL-3015 GE Rotterdam, Netherlands.
[Bierut, Laura J.; Rice, John P.] Washington Univ, Dept Psychiat, St Louis, MO 63110 USA.
[Byrne, Enda M.] Univ Queensland, Queensland Brain Inst, St Lucia, Qld 4072, Australia.
[Byrne, Enda M.] QIMR Berghofer Med Res Inst, Brisbane, Qld 4006, Australia.
[Hottenga, Jouke-Jan; de Geus, Eco E. J.; Willemsen, Gonneke; Boomsma, Dorret I.] Vrije Univ Amsterdam, Dept Biol Psychol, NL-1081 BT Amsterdam, Netherlands.
[Koller, Daniel L.; Foroud, Tatiana; Econs, Michael J.] Indiana Univ, Sch Med, Dept Med & Mol Genet, Indianapolis, IN 46202 USA.
[Pers, Tune H.] Board Inst, Cambridge, MA 02142 USA.
[Pers, Tune H.] Tech 142 Univ Denmark, Dept Syst Biol, Ctr Biol Sequence Anal, DK-2800 Lyngby, Denmark.
[Yerges-Armstrong, Laura M.; McArdle, Patrick F.; Streeten, Elizabeth A.] Univ Maryland, Sch Med, Program Personalized & Genom Med, Baltimore, MD 21201 USA.
[Yerges-Armstrong, Laura M.; McArdle, Patrick F.; Streeten, Elizabeth A.] Univ Maryland, Sch Med, Dept Med, Div Endocrinol Diabet & Nutr, Baltimore, MD 21201 USA.
[Andrulis, Irene L.] Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, Ontario Canc Genet Network, Toronto, ON M5G 1X5, Canada.
[Andrulis, Irene L.] Univ Toronto, Dept Mol Genet, Toronto, ON M5S 1A8, Canada.
[Anton-Culver, Hoda] Univ Calif Irvine, Dept Epidemiol, Irvine, CA 92697 USA.
[Atsma, Femke] Sanquin Res, NL-6525 GA Nijmegen, Netherlands.
[Bandinelli, Stefania] Tuscany Reg Hlth Agcy, Florence, Italy.
[Bandinelli, Stefania] Univ Florence, Dept Med & Surg Crit Care, I-50134 Florence, Italy.
[Bandinelli, Stefania] Azienda Sanit Firenze, Geriatr Unit, I-50122 Florence, Italy.
[Beckmann, Matthias W.; Fasching, Peter A.] Univ Erlangen Nurnberg, Comprehens Canc Ctr Erlangen EMN, Univ Hosp Erlangen, Univ Breast Ctr Franconia,Dept Gynecol & Obstet, D-91054 Erlangen, Germany.
[Benitez, Javier] Spanish Natl Canc Res Ctr CNIO, Human Canc Genet Program, Human Genet Grp, E-28029 Madrid, Spain.
[Benitez, Javier] Ctr Invest Red Enfermed Raras CIBERER, E-46010 Valencia, Spain.
[Blomqvist, Carl] Univ Helsinki, Dept Oncol, FI-00100 Helsinki, Finland.
[Blomqvist, Carl] Univ Helsinki, Cent Hosp, FI-00100 Helsinki, Finland.
[Bojesen, Stig E.] Univ Copenhagen, Univ Copenhagen Hosp, Herlev Hosp, Copenhagen Gen Populat Study, DK-2100 Copenhagen, Denmark.
[Bojesen, Stig E.] Univ Copenhagen, Copenhagen Univ Hosp, Herlev Hosp, Dept Clin Biochem, DK-2100 Copenhagen, Denmark.
[Bonanni, Bernardo] Ist Europeo Oncol IEO, Div Canc Prevent & Genet, I-20139 Milan, Italy.
[Brauch, Hiltrud] Dr Margarete Fischer Bosch Inst Clin Pharmacol, D-70376 Stuttgart, Germany.
[Brauch, Hiltrud] Univ Tubingen, D-72074 Tubingen, Germany.
[Brenner, Hermann; Dieffenbach, Aida K.] German Canc Res Ctr, Div Clin Epidemiol & Aging Res, D-69120 Heidelberg, Germany.
[Brenner, Hermann; Dieffenbach, Aida K.] German Canc Consortium DKTK, D-69120 Heidelberg, Germany.
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[Chanock, Stephen] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Chen, Jinhui] Indiana Univ, Sch Med, Dept Anat, Indianapolis, IN 46202 USA.
[Chen, Jinhui] Indiana Univ, Sch Med, Dept Neurol Surg, Indianapolis, IN 46202 USA.
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[Chenevix-Trench, Georgia; Martin, Nicholas G.] QIMR Berghofer Med Res Inst, Dept Genet, Brisbane, Qld 4006, Australia.
[Collee, J. Margriet] Erasmus Univ, Med Ctr, Dept Clin Genet, NL-3000 CA Rotterdam, Netherlands.
[Couch, Fergus J.] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN 55905 USA.
[Couper, David] Univ N Carolina, Dept Biostat, Chapel Hill, NC 27599 USA.
[Coviello, Andrea D.] Boston Univ, Sch Med, Dept Med, Sect Prevent Med, Boston, MA 02118 USA.
[Coviello, Andrea D.] Boston Univ, Sch Med, Dept Med, Endocrinol Sect, Boston, MA 02118 USA.
[Cox, Angela] Univ Sheffield, Dept Oncol, Sheffield Canc Res Ctr, Sheffield S10 2RX, S Yorkshire, England.
[D'adamo, Adamo Pio; Robino, Antonietta; Gasparini, Paolo] Univ Trieste, Dept Clin Med Sci Surg & Hlth, I-34149 Trieste, Italy.
[De Vivo, Immaculata; Hu, Frank B.; Hunter, David J.; Stampfer, Meir J.; Kraft, Peter] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
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[Demerath, Ellen W.] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN 55455 USA.
[Devilee, Peter] Leiden Univ, Med Ctr, Dept Human Genet, NL-2300 RC Leiden, Netherlands.
[Devilee, Peter] Leiden Univ, Med Ctr, Dept Pathol, NL-2300 RC Leiden, Netherlands.
[Dunning, Alison M.; Pharoah, Paul D. P.; Tyrer, Jonathan] Univ Cambridge, Dept Oncol, Ctr Canc Genet Epidemiol, Cambridge CB2 1TN, England.
[Eriksson, Johan G.; Pouta, Anneli; Salomaa, Veikko] Natl Inst Hlth & Welf, FI-00271 Helsinki, Finland.
[Eriksson, Johan G.] Univ Helsinki, Dept Gen Practice & Primary Hlth Care, FI-00014 Helsinki, Finland.
[Eriksson, Johan G.] Univ Helsinki, Cent Hosp, Unit Gen Practice, FI-00029 Hus Helsinki, Finland.
[Eriksson, Johan G.] Folkhalsan Res Ctr, FI-00290 Helsinki, Finland.
[Ferrucci, Luigi] NIA, Longitudinal Studies Sect, Clin Res Branch, Gerontol Res Ctr, Bethesda, MD 20892 USA.
[Flesch-Janys, Dieter] Univ Clin Hamburg Eppendorf, Dept Canc Epidemiol, Clin Canc Registry, D-20246 Hamburg, Germany.
[Flesch-Janys, Dieter] Univ Clin Hamburg Eppendorf, Inst Med Biometr & Epidemiol, D-20246 Hamburg, Germany.
[Flyger, Henrik] Univ Copenhagen Hosp, Herlev Hosp, Dept Breast Surg, DK-2100 Copenhagen, Denmark.
[Franke, Lude] Univ Groningen, Univ Med Ctr Groningen, Dept Genet, NL-9700 AB Groningen, Netherlands.
[Garcia, Melissa E.; Harris, Tamara B.] NIA, NIH, Bethesda, MD 20892 USA.
[Garcia-Closas, Montserrat] Inst Canc Res, Div Genet & Epidemiol, Sutton SM2 5NG, Surrey, England.
[Garcia-Closas, Montserrat] Inst Canc Res, Div Breast Canc Res, Breakthrough Breast Canc Res Ctr, London SW3 6JB, England.
[de Geus, Eco E. J.] Vrije Univ Amsterdam, Med Ctr, EMGO Inst Hlth & Care Res, NL-1081 BI Amsterdam, Netherlands.
[Giles, Graham G.; Milne, Roger L.] Canc Council Victoria, Canc Epidemiol Ctr, Melbourne, Vic 3004, Australia.
[Giles, Graham G.; Hopper, John L.; Milne, Roger L.] Univ Melbourne, Melbourne Sch Populat & Global Hlth, Ctr Epidemiol & Biostat, Melbourne, Vic 3010, Australia.
[Thorsteinsdottir, Unnur; Stefansson, Kari] Univ Iceland, Fac Med, IS-101 Reykjavik, Iceland.
[Gudbjartsson, Daniel F.; Guenel, Pascal] INSERM Natl Inst Hlth & Med Res, CESP Ctr Res Epidemiol & Populat Hlth, U1018, F-94807 Villejuif, France.
[Guenel, Pascal] Univ Paris Sud, UMRS 1018, F-94807 Villejuif, France.
[Guo, Suiqun] Southern Med Univ, Dept Obstet & Gynecol, Guangzhou 510515, Guangdong, Peoples R China.
[Hamann, Ute] Deutsch Krebsforsch Zentrum DKFZ, D-69120 Heidelberg, Germany.
[Haring, Robin; Wallaschofski, Henri] Univ Med Greifswald, Inst Clin Chem, D-17475 Greifswald, Germany.
[Haring, Robin; Wallaschofski, Henri] Univ Med Greifswald, Lab Med, D-17475 Greifswald, Germany.
[Hartman, Catharina A.] Univ Groningen, Univ Med Ctr Groningen, Dept Psychiat, NL-9700 AB Groningen, Netherlands.
[Heath, AndrewC.] Washington Univ, Dept Psychiat, St Louis, MO 63110 USA.
[Hofman, Albert; Rivadeneira, Fernando; Uitterlinden, Andre G.] Erasmus MC, Dept Epidemiol, NL-3000 CA Rotterdam, Netherlands.
[Hooning, Maartje J.] Erasmus Univ, Med Ctr, Dept Med Oncol, NL-3000 CA Rotterdam, Netherlands.
[Hu, Frank B.; Stampfer, Meir J.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
[Karasik, David; Kiel, Douglas P.] Hebrew Senior Life Inst Aging Res, Boston, MA 02131 USA.
[Kiel, Douglas P.] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02115 USA.
[Kiel, Douglas P.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Knight, Julia A.] Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, Toronto, ON M5G 1X5, Canada.
[Knight, Julia A.] Univ Toronto, Dalla Lana Sch Publ Hlth, Div Epidemiol, Toronto, ON M5T 3M7, Canada.
[Kosma, Veli-Matti; Mannermaa, Arto] Univ Eastern Finland, Inst Clin Med Pathol & Forens Med, Sch Med, FI-70211 Kuopio, Finland.
[Kosma, Veli-Matti; Mannermaa, Arto] Kuopio Univ Hosp, Dept Clin Pathol, Imaging Ctr, FI-70029 Kuopio, Finland.
[Lambrechts, Diether] VIB, Vesalius Res Ctr VRC, B-3000 Louvain, Belgium.
[Lambrechts, Diether] Univ Leuven, Dept Oncol, Lab Translat Genet, B-3000 Louvain, Belgium.
[Lindblom, Annika] Karolinska Inst, Dept Mol Med & Surg, SE-17177 Stockholm, Sweden.
[Melbye, Mads] Stanford Univ, Sch Med, Dept Med, Stanford, CA 94305 USA.
[Nevanlinna, Heli] Univ Helsinki, Dept Obstet & Gynecol, FI-00029 Hus Helsinki, Finland.
[Nevanlinna, Heli] Univ Helsinki, Cent Hosp, FI-00029 Hus Helsinki, Finland.
[Neven, Patrick] KULeuven Univ Leuven, Dept Oncol, Multidisciplinary Breast Ctr, Univ Hosp Leuven, B-3000 Louvain, Belgium.
[Nohr, Ellen A.] Univ Southern Denmark, Inst Clin Res, Res Unit Obstet & Gynecol, DK-5000 Odense C, Denmark.
[Oldehinkel, Albertine J.] Univ Groningen, Univ Med Ctr Groningen, Interdisciplinary Ctr Psychopathol & Emot Regulat, NL-9700 RB Groningen, Netherlands.
[Palotie, Aarno] Massachusetts Gen Hosp, Dept Med, Analyt & Translat Genet Unit, Boston, MA 02114 USA.
[Palotie, Aarno] Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA.
[Palotie, Aarno] Massachusetts Gen Hosp, Dept Psychiat, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA.
[Peacock, Munro; Storniolo, Anna M.; Econs, Michael J.] Indiana Univ, Sch Med, Dept Med, Indianapolis, IN 46202 USA.
[Peterlongo, Paolo] Fdn Ist FIRC Oncol Mol, IFOM, I-20139 Milan, Italy.
[Peto, Julian] Univ London London Sch Hyg & Trop Med, Noncommunicable Dis Epidemiol Dept, London WC1E 7HT, England.
[Postma, Dirkje S.] Univ Groningen, Univ Med Ctr Groningen, Dept Pulm Med & TB, GRIAC Res Inst, NL-9700 RB Groningen, Netherlands.
[Pouta, Anneli] Oulu Univ Hosp, Dept Obstet & Gynecol, FI-90029 Oys Oulu, Finland.
[Pylkaes, Katri; Winqvist, Robert] Univ Oulu, Oulu Univ Hosp, NordLab Oulu, Lab Canc Genet & Tumor Biol,Dept Clin Chem, FI-90014 Oulu, Finland.
[Pylkaes, Katri; Winqvist, Robert] Univ Oulu, Oulu Univ Hosp, NordLab Oulu, Bioctr Oulu, FI-90014 Oulu, Finland.
[Radice, Paolo] Fdn IRCCS Ist Nazl Tumori INT, Dept Prevent & Predict Med, Unit Mol Bases Genet Risk & Genet Testing, I-20133 Milan, Italy.
[Schlessinger, David] NIA, Intramural Res Program, Baltimore, MD 21224 USA.
[Schmidt, Marjanka K.] Antoni van Leeuwenhoek Hosp, Netherlands Canc Inst, NL-1006 BE Amsterdam, Netherlands.
[Southey, Mellissa C.] Univ Melbourne, Dept Pathol, Melbourne, Vic 3010, Australia.
[Sovio, Ulla; Jaervelin, Marjo-Riitta] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Ctr Environm & Hlth, MRC Hlth Protect Agcy HPA,Dept Epidemiol & Biosta, London W2 1PG, England.
[Sovio, Ulla] Univ Cambridge, Dept Obstet & Gynaecol, Cambridge CB2 0SW, England.
[Stoeckl, Doris] Helmholtz Zentrum Munchen German Res Ctr Environm, Inst Epidemiol 2, D-8576 Neuherberg, Germany.
[Stoeckl, Doris] Univ Munich, Dept Obstet & Gynaecol, D-81377 Munich, Germany.
[Vollenweider, Peter; Waeber, Gerard] Univ Lausanne Hosp, Dept Internal Med, CH-1015 Lausanne, Switzerland.
[Voelzke, Henry] Univ Med Greifswald, Inst Community Med, D-17475 Greifswald, Germany.
[Voelzke, Henry; Wallaschofski, Henri] DZHK German Ctr Cardiovasc Res, Partner Site Greifswald, D-17475 Greifswald, Germany.
[Waldenberger, Melanie] Helmholtz Zentrum Munchen German Res Ctr Environm, Res Unit Mol Epidemiol, D-8576 Neuherberg, Germany.
[Wolffenbuttel, Bruce H. R.] Univ Groningen, Univ Med Ctr Groningen, Dept Endocrinol, NL-9700 AB Groningen, Netherlands.
[Wright, Margaret J.; Montgomery, Grant W.] Queensland Inst Med Res, Brisbane, Qld 4029, Australia.
[Khaw, Kay-Tee] Univ Cambridge, Inst Publ Hlth, Dept Publ Hlth & Primary Care, Cambridge CB2 0QQ, England.
[Loos, Ruth J. F.] Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, Mindich Child Hlth & Dev Inst, Dept Prevent Med,Genet Obes & Related Metab Trait, New York, NY 10029 USA.
[McCarthy, Mark I.] Churchill Hosp, NIHR Oxford Biomed Res Ctr, Oxford OX3 7LE, England.
[McCarthy, Mark I.] Univ Oxford, Churchill Hosp, Oxford Ctr Diabet Endocrinol & Metab, Oxford OX3 7LJ, England.
[Streeten, Elizabeth A.] Geriatr Res & Educ Clin Ctr GRECC, Vet Adm Med Ctr, Baltimore, MD 21201 USA.
[van Duijn, Cornelia M.] Ctr Med Syst Biol, NL-2300 RC Leiden, Netherlands.
[Boerwinkle, Eric] Univ Houston, Human Genet Ctr & Divof Epidemiol, Houston, TX 77025 USA.
[Ingelsson, Erik] Uppsala Univ, Mol Epidemiol & Sci Life Lab, Dept Med Sci, S-75105 Uppsala, Sweden.
[Jaervelin, Marjo-Riitta] Univ Oulu, Inst Hlth Sci, FI-90014 Oulu, Finland.
[Jaervelin, Marjo-Riitta] Univ Oulu, Bioctr Oulu, FI-90014 Oulu, Finland.
[Jaervelin, Marjo-Riitta] Natl Inst Hlth & Welf, Dept Children & Young People & Families, FI-90101 Oulu, Finland.
[Jaervelin, Marjo-Riitta] Oulu Univ Hosp, Unit Primary Care, FI-90220 Oulu, Finland.
[Kraft, Peter] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
[Sorensen, Thorkild I. A.] Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn Ctr Basic Metab Res, DK-2200 Copenhagen, Denmark.
[Sorensen, Thorkild I. A.] Capital Reg, Bispebjerg & Frederiksberg Hosp, Inst Prevent Med, DK-2000 Frederiksberg, Denmark.
[Strachan, David P.] Univ London, Div Populat Hlth Sci & Educ, London SW17 0RE, England.
[Zygmunt, Marek] Univ Med Greifswald, Dept Obstet & Gynecol, D-17475 Greifswald, Germany.
[Murabito, Joanne M.] Boston Univ, Sch Med, Dept Med, Gen Internal Med Sect, Boston, MA 02118 USA.
[Ong, Ken K.] Univ Cambridge, Dept Paediat, Cambridge CB2 0QQ, England.
RP Perry, JRB (reprint author), Univ Cambridge, Sch Clin Med, MRC Epidemiol Unit, Inst Metab Sci, Box 285 Cambridge Biomed Campus, Cambridge CB2 0QQ, England.
EM john.perry@mrc-epid.cam.ac.uk; Murabito@bu.edu
RI Magnusson, Patrik/C-4458-2017; Grioni, Sara/K-5320-2016; Wright,
Margaret/A-4560-2016; Fox, Laura /C-6249-2016; Bowtell,
David/H-1007-2016; Smith, Albert/K-5150-2015; mangino,
massimo/F-5134-2011; d'Adamo, Adamo Pio/G-4064-2011; Johnson,
Andrew/G-6520-2013; Franke, Lude/P-7036-2016; Ormel, Johan/C-6094-2013;
Wijmenga, Cisca/D-2173-2009; Davey Smith, George/A-7407-2013; Brenner,
Hermann/B-4627-2017; Stockl, Doris/B-5352-2014; Hypponen,
Elina/B-2596-2014; Knight, Julia/A-6843-2012; Colaus,
PsyColaus/K-6607-2013; Visser, Jenny /F-8156-2011; Garcia-Closas,
Montserrat /F-3871-2015; Gudnason, Vilmundur/K-6885-2015; Pahkala,
Katja/D-7449-2013; Ripatti, Samuli/H-9446-2014; Atsma, F./L-4178-2015;
Montgomery, Grant/B-7148-2008; Deloukas, Panos/B-2922-2013; Rivadeneira,
Fernando/O-5385-2015
OI de Geus, Eco/0000-0001-6022-2666; Martin, Nicholas/0000-0003-4069-8020;
Dobrovic, Alexander/0000-0003-3414-112X; Ganna,
Andrea/0000-0002-8147-240X; Jarvelin, Marjo-Riitta/0000-0002-2149-0630;
Cox, Angela/0000-0002-5138-1099; Timpson, Nicholas/0000-0002-7141-9189;
Lawlor, Debbie A/0000-0002-6793-2262; Dunning, Alison
Margaret/0000-0001-6651-7166; Eriksson, Johan/0000-0002-2516-2060;
Giles, Graham/0000-0003-4946-9099; Bergmann, Sven/0000-0002-6785-9034;
Paternoster, Lavinia/0000-0003-2514-0889; Gieger,
Christian/0000-0001-6986-9554; Zeggini, Eleftheria/0000-0003-4238-659X;
Kiel, Douglas/0000-0001-8474-0310; Sacerdote,
Carlotta/0000-0002-8008-5096; Karasik, David/0000-0002-8826-0530;
Wolffenbuttel, Bruce H.R./0000-0001-9262-6921; Forouhi,
Nita/0000-0002-5041-248X; Grioni, Sara/0000-0002-5891-8426; Devilee,
Peter/0000-0002-8023-2009; Day, Felix/0000-0003-3789-7651; Murray,
Anna/0000-0002-2351-2522; Esko, Tonu/0000-0003-1982-6569; Franks,
Paul/0000-0002-0520-7604; Nevanlinna, Heli/0000-0002-0916-2976; Ziad
Alizadeh, Behrooz/0000-0002-1415-8007; Magi, Reedik/0000-0002-2964-6011;
Czene, Kamila/0000-0002-3233-5695; Wright, Margaret/0000-0001-7133-4970;
Bowtell, David/0000-0001-9089-7525; Smith, Albert/0000-0003-1942-5845;
mangino, massimo/0000-0002-2167-7470; d'Adamo, Adamo
Pio/0000-0001-9367-4909; Franke, Lude/0000-0002-5159-8802; Davey Smith,
George/0000-0002-1407-8314; Brenner, Hermann/0000-0002-6129-1572;
Hypponen, Elina/0000-0003-3670-9399; Garcia-Closas, Montserrat
/0000-0003-1033-2650; Gudnason, Vilmundur/0000-0001-5696-0084; Ripatti,
Samuli/0000-0002-0504-1202; Montgomery, Grant/0000-0002-4140-8139;
Deloukas, Panos/0000-0001-9251-070X; Rivadeneira,
Fernando/0000-0001-9435-9441
FU Cancer Research UK [10118, 10124]; Medical Research Council [G0401527,
G0701863, G1000143, G9815508, MC_PC_15018, MC_U106179471, MC_U106179472,
MC_UU_12013/1, MC_UU_12013/3, MC_UU_12015/1, MC_UU_12015/2,
MR/J012165/1]; NCATS NIH HHS [UL1 TR001108]; NCI NIH HHS [P50 CA116201];
NIA NIH HHS [R01 AG041517, U01 AG049505]; NINDS NIH HHS [R01 NS017950];
Wellcome Trust [102215, 098381]
NR 77
TC 95
Z9 95
U1 9
U2 77
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 OCT 2
PY 2014
VL 514
IS 7520
BP 92
EP +
DI 10.1038/nature13545
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AP9SS
UT WOS:000342420800042
PM 25231870
ER
PT J
AU Santos, MA
Faryabi, RB
Ergen, AV
Day, AM
Malhowski, A
Canela, A
Onozawa, M
Lee, JE
Callen, E
Gutierrez-Martinez, P
Chen, HT
Wong, N
Finkel, N
Deshpande, A
Sharrow, S
Rossi, DJ
Ito, K
Ge, K
Aplan, PD
Armstrong, SA
Nussenzweig, A
AF Santos, Margarida A.
Faryabi, Robert B.
Ergen, Aysegul V.
Day, Amanda M.
Malhowski, Amy
Canela, Andres
Onozawa, Masahiro
Lee, Ji-Eun
Callen, Elsa
Gutierrez-Martinez, Paula
Chen, Hua-Tang
Wong, Nancy
Finkel, Nadia
Deshpande, Aniruddha
Sharrow, Susan
Rossi, Derrick J.
Ito, Keisuke
Ge, Kai
Aplan, Peter D.
Armstrong, Scott A.
Nussenzweig, Andre
TI DNA-damage-induced differentiation of leukaemic cells as an anti-cancer
barrier
SO NATURE
LA English
DT Article
ID HEMATOPOIETIC STEM-CELLS; OXIDATIVE STRESS; RNA-SEQ; MLL; PROGENITORS;
BREAKS; RESISTANCE; DISCOVERY; LYMPHOMA; RENEWAL
AB Self-renewal is the hallmark feature both of normal stem cells and cancer stem cells(1). Since the regenerative capacity of normal haematopoietic stem cells is limited by the accumulation of reactive oxygen species and DNA double-strand breaks(2-4), we speculated that DNA damage might also constrain leukaemic self-renewal and malignant haematopoiesis. Here we show that the histone methyl-transferase MLL4, a suppressor of B-cell lymphoma(5,6), is required for stem-cell activity and an aggressive form of acutemyeloid leukaemia harbouring the MLL-AF9 oncogene. Deletion of MLL4 enhances myelopoiesis and myeloid differentiation of leukaemic blasts, which protects mice from death related to acute myeloid leukaemia. MLL4 exerts its function by regulating transcriptional programs associated with the antioxidant response. Addition of reactive oxygen species scavengers or ectopic expression of FOXO3 protects MLL-/- MLL-AF9 cells from DNA damage and inhibits myeloid maturation. Similar to MLL4 deficiency, loss of ATM or BRCA1 sensitizes transformed cells to differentiation, suggesting that myeloid differentiation is promoted by loss of genome integrity. Indeed, we show that restriction-enzyme-induced double-strand breaks are sufficient to induce differentiation of MLL-AF9 blasts, which requires cyclin-dependent kinase inhibitor p21(Cip1) (Cdkn1a) activity. In summary, we have uncovered an unexpected tumour-promoting role of genome guardians in enforcing the oncogene-induced differentiation blockade in acute myeloid leukaemia.
C1 [Santos, Margarida A.; Faryabi, Robert B.; Ergen, Aysegul V.; Day, Amanda M.; Malhowski, Amy; Canela, Andres; Callen, Elsa; Chen, Hua-Tang; Wong, Nancy; Finkel, Nadia; Nussenzweig, Andre] NCI, Lab Genome Integr, NIH, Bethesda, MD 20892 USA.
[Onozawa, Masahiro; Aplan, Peter D.] NCI, Genet Branch, NIH, Bethesda, MD 20892 USA.
[Lee, Ji-Eun; Ge, Kai] NIDDKD, Lab Endocrinol & Receptor Biol, NIH, Bethesda, MD 20892 USA.
[Gutierrez-Martinez, Paula; Rossi, Derrick J.] Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA.
[Gutierrez-Martinez, Paula; Rossi, Derrick J.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA.
[Deshpande, Aniruddha; Armstrong, Scott A.] Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, New York, NY 10065 USA.
[Deshpande, Aniruddha; Armstrong, Scott A.] Mem Sloan Kettering Canc Ctr, Dept Pediat, New York, NY 10065 USA.
[Sharrow, Susan] NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA.
[Ito, Keisuke] Albert Einstein Coll Med, Ruth L & David S Gottesman Inst Stem Cell & Regen, Dept Cell Biol, Bronx, NY 10461 USA.
[Ito, Keisuke] Albert Einstein Coll Med, Dept Med, Albert Einstein Canc Ctr, Bronx, NY 10461 USA.
RP Nussenzweig, A (reprint author), NCI, Lab Genome Integr, NIH, Bethesda, MD 20892 USA.
EM andre_nussenzweig@nih.gov
RI Lee, Ji-Eun/F-7891-2011; Faryabi, Robert/H-3544-2015; Aplan,
Peter/K-9064-2016;
OI Lee, Ji-Eun/0000-0002-3768-7016; Faryabi, Robert/0000-0002-7931-2175;
Ge, Kai/0000-0002-7442-5138
FU Leukemia and Lymphoma Society; National Cancer Institute [CA66996,
CA140575]; National Institutes of Health; National Cancer Institute;
Center for Cancer Research; Ellison Medical Foundation
FX We thank all members of the A. Nussenzweig laboratory, J. Daniel and P.
Love for discussions; L. Granger for flow cytometry; M. J. Kruhlak for
microscopy; K. Zhao for RNA sequencing; R. Anderson and K. Smith for
animal care; K. Naka for the FOXO3 retrovirus; G. Legube for the
pBABE-AsiSI-ER plasmid; J. Zuber for pLEPG and pRT3GEPIR plasmids; O.
Fernandez-Capetillo for ATRi; and S. John for suggestions. S. A. A. was
supported by the Leukemia and Lymphoma Society and National Cancer
Institute grants CA66996 and CA140575. This work was supported by the
Intramural Research Program of the National Institutes of Health, the
National Cancer Institute and the Center for Cancer Research, and an
Ellison Medical Foundation Senior Scholar in Aging Award to A.N.
NR 40
TC 41
Z9 42
U1 4
U2 59
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 OCT 2
PY 2014
VL 514
IS 7520
BP 107
EP +
DI 10.1038/nature13483
PG 23
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AP9SS
UT WOS:000342420800045
PM 25079327
ER
PT J
AU Wood, AR
Tuke, MA
Nalls, MA
Hernandez, DG
Bandinelli, S
Singleton, AB
Melzer, D
Ferrucci, L
Frayling, TM
Weedon, MN
AF Wood, Andrew R.
Tuke, Marcus A.
Nalls, Mike A.
Hernandez, Dena G.
Bandinelli, Stefania
Singleton, Andrew B.
Melzer, David
Ferrucci, Luigi
Frayling, Timothy M.
Weedon, Michael N.
TI Another explanation for apparent epistasis
SO NATURE
LA English
DT Letter
ID ASSOCIATIONS
C1 [Wood, Andrew R.; Tuke, Marcus A.; Melzer, David; Frayling, Timothy M.; Weedon, Michael N.] Univ Exeter, Sch Med, Inst Biomed & Clin Sci, Exeter EX2 5DW, Devon, England.
[Nalls, Mike A.; Hernandez, Dena G.; Singleton, Andrew B.] NIA, Neurogenet Lab, Bethesda, MD 20892 USA.
[Hernandez, Dena G.] UCL, Dept Mol Neurosci, London WC1N 1PJ, England.
[Hernandez, Dena G.] UCL, Reta Lila Labs, Inst Neurol, London WC1N 1PJ, England.
[Bandinelli, Stefania] Tuscany Reg Hlth Agcy, Florence, Italy.
[Bandinelli, Stefania] Univ Florence, Dept Med & Surg Crit Care, Florence, Italy.
[Bandinelli, Stefania] Azienda Sanitaria Firenze, Geriatr Unit, Florence, Italy.
[Ferrucci, Luigi] NIA, Longitudinal Studies Sect, Clin Res Branch, Gerontol Res Ctr, Baltimore, MD 21225 USA.
RP Wood, AR (reprint author), Univ Exeter, Sch Med, Inst Biomed & Clin Sci, Exeter EX2 5DW, Devon, England.
EM T.M.Frayling@exeter.ac.uk; M.N.Weedon@exeter.ac.uk
RI Singleton, Andrew/C-3010-2009;
OI Melzer, David/0000-0002-0170-3838
FU Medical Research Council [G0500070]
NR 8
TC 16
Z9 16
U1 0
U2 8
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 OCT 2
PY 2014
VL 514
IS 7520
BP E3
EP E5
DI 10.1038/nature13691
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AP9SS
UT WOS:000342420800003
PM 25279928
ER
PT J
AU Prasad, V
AF Prasad, Vinay
TI Exemestane with Ovarian Suppression in Premenopausal Breast Cancer
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Letter
C1 NIH, Bethesda, MD 20892 USA.
RP Prasad, V (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA.
EM vinayak.prasad@nih.gov
NR 1
TC 0
Z9 0
U1 0
U2 1
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
EI 1533-4406
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD OCT 2
PY 2014
VL 371
IS 14
BP 1358
EP 1358
PG 1
WC Medicine, General & Internal
SC General & Internal Medicine
GA AP9VS
UT WOS:000342429800018
PM 25271613
ER
PT J
AU Wang, C
Chao, ZM
Sun, W
Wu, XY
Ito, Y
AF Wang, Chun
Chao, Zhimao
Sun, Wen
Wu, Xiaoyi
Ito, Yoichiro
TI ISOLATION OF FIVE GLYCOSIDES FROM THE BARKS OF ILEX ROTUNDA BY
HIGH-SPEED COUNTER-CURRENT CHROMATOGRAPHY
SO JOURNAL OF LIQUID CHROMATOGRAPHY & RELATED TECHNOLOGIES
LA English
DT Article
DE pedunculoside; Ilex rotunda; glycoside; syringaresinol 4 ',4
''-di-O-beta-D-glucopyranoside; high-speed counter-current
chromatography (HSCCC); two-phase solvent system
ID PREPARATIVE ISOLATION; PURIFICATION; SEPARATION; CONSTITUENTS;
PEDUNCULOSIDE; SAPONINS; BENTH; HSCCC; ROOT
AB Semi-preparative and preparative high-speed counter-current chromatography (HSCCC) were successfully used for isolation of five glycosides from 50% ethanol extract of the dried barks of Ilex rotunda Thunb. (Aquifoliaceae) by using a two-phase solvent system composed of ethyl acetate-n-butanol-water (1:6:7, v/v/v). From 1.0g of the extract, syringaresinol 4 ',4 ''-di-O-beta-D-glucopyranoside ( I , 20.2mg, 55.4% purity), syringin ( II , 56.8mg, 98.1% purity), sinapaldehyde glucoside ( III , 26.2mg, 68.6% purity), syringaresinol 4 '-O-beta-D-glucopyranoside ( IV , 20.4mg, 95.3% purity), and pedunculoside ( V , 45.1mg, 97.3% purity) were obtained by one run of TBE-1000A HSCCC instrument with 1000mL of column volume. Glycosides I (9.8mg, 95.5% purity) and III (14.2mg, 97.8% purity) were further purified by preparative high performance liquid chromatography (HPLC). Their structures were identified by IR, MS, and H-1 and C-13 NMR studies. Glycoside I was isolated from this plant for the first time.
C1 [Wang, Chun; Chao, Zhimao; Sun, Wen; Wu, Xiaoyi] China Acad Chinese Med Sci, Inst Chinese Mat Med, Beijing 100700, Peoples R China.
[Ito, Yoichiro] NHLBI, Lab Bioseparat Technol, Biochem & Biophys Ctr, NIH, Bethesda, MD 20892 USA.
RP Chao, ZM (reprint author), China Acad Chinese Med Sci, Inst Chinese Mat Med, Beijing 100700, Peoples R China.
EM chaozhimao@icmm.ac.cn
FU Public Welfare Research Special Project from the General Administration
of Quality Supervision, Inspection, and Quarantine of the People's
Republic of China [201210209]
FX The authors gratefully acknowledge the financial support of the Public
Welfare Research Special Project from the General Administration of
Quality Supervision, Inspection, and Quarantine of the People's Republic
of China (No. 201210209).
NR 37
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U2 51
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 520 CHESTNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA
SN 1082-6076
EI 1520-572X
J9 J LIQ CHROMATOGR R T
JI J. Liq. Chromatogr. Relat. Technol.
PD OCT 2
PY 2014
VL 37
IS 16
BP 2363
EP 2376
DI 10.1080/10826076.2013.832297
PG 14
WC Biochemical Research Methods; Chemistry, Analytical
SC Biochemistry & Molecular Biology; Chemistry
GA AG0QC
UT WOS:000335119000010
PM 25132792
ER
PT J
AU Assadipour, Y
Azoury, SC
Schaub, NN
Hong, Y
Eil, R
Inchauste, SM
Steinberg, SM
Venkatesan, AM
Hughes, MS
Libutti, SK
AF Assadipour, Yasmine
Azoury, Said C.
Schaub, Nicholas N.
Hong, Young
Eil, Robert
Inchauste, Suzanne M.
Steinberg, Seth M.
Venkatesan, Aradhana M.
Hughes, Marybeth S.
Libutti, Steven K.
TI Significance of pre-operative radiographic pancreatic density in
predicting pancreatic fistula after surgery for pancreatic
neuroendocrine tumors
SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS
LA English
DT Meeting Abstract
CT 100th Annual Clinical Congress of the American-College-of-Surgeons
CY OCT 26-30, 2014
CL San Francisco, CA
SP Amer Coll Surg
C1 Albert Einstein Coll Med, Bronx, NY 10467 USA.
NCI, Bethesda, MD 20892 USA.
NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1072-7515
EI 1879-1190
J9 J AM COLL SURGEONS
JI J. Am. Coll. Surg.
PD OCT
PY 2014
VL 219
IS 4
SU S
BP E112
EP E112
PG 1
WC Surgery
SC Surgery
GA CR1UU
UT WOS:000361111400267
ER
PT J
AU Brat, G
Smith, DJ
Tong, DD
Huang, Y
Grahammer, J
Nagy, K
Brandacher, G
Schneider, JP
AF Brat, Gabriel
Smith, Daniel J.
Tong, Dedi
Huang, Yong
Grahammer, Johanna
Nagy, Katelyn
Brandacher, Gerald
Schneider, Joel P.
TI Design of a light-controlled reverse phase transition hydrogel for use
in vascular anastomosis
SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS
LA English
DT Meeting Abstract
CT 100th Annual Clinical Congress of the American-College-of-Surgeons
CY OCT 26-30, 2014
CL San Francisco, CA
SP Amer Coll Surg
C1 Johns Hopkins Univ, Baltimore, MD USA.
NIH, Bethesda, MD 20892 USA.
RI Brandacher, Gerald/L-7540-2016
NR 0
TC 0
Z9 0
U1 1
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1072-7515
EI 1879-1190
J9 J AM COLL SURGEONS
JI J. Am. Coll. Surg.
PD OCT
PY 2014
VL 219
IS 4
SU S
BP E90
EP E91
PG 2
WC Surgery
SC Surgery
GA CR1UU
UT WOS:000361111400210
ER
PT J
AU Nilubol, N
Kebebew, E
AF Nilubol, Naris
Kebebew, Electron
TI Should small thyroid cancer be observed? A population-based study of
non-medullary thyroid cancer-related mortality
SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS
LA English
DT Meeting Abstract
CT 100th Annual Clinical Congress of the American-College-of-Surgeons
CY OCT 26-30, 2014
CL San Francisco, CA
SP Amer Coll Surg
C1 [Nilubol, Naris; Kebebew, Electron] NCI, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1072-7515
EI 1879-1190
J9 J AM COLL SURGEONS
JI J. Am. Coll. Surg.
PD OCT
PY 2014
VL 219
IS 4
SU S
BP E85
EP E85
PG 1
WC Surgery
SC Surgery
GA CR1UU
UT WOS:000361111400197
ER
PT J
AU Nilubol, N
Weinsten, LS
Simonds, WF
Libutti, SK
Marx, SJ
Kebebew, E
AF Nilubol, Naris
Weinsten, Lee S.
Simonds, William F.
Libutti, Steven K.
Marx, Stephen J.
Kebebew, Electron
TI Limited parathyroidectomy in multiple endocrine neoplasia type 1
associated primary hyperparathyroidism: a set up for failure
SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS
LA English
DT Meeting Abstract
CT 100th Annual Clinical Congress of the American-College-of-Surgeons
CY OCT 26-30, 2014
CL San Francisco, CA
SP Amer Coll Surg
C1 [Nilubol, Naris; Weinsten, Lee S.; Simonds, William F.; Libutti, Steven K.; Marx, Stephen J.; Kebebew, Electron] NCI, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1072-7515
EI 1879-1190
J9 J AM COLL SURGEONS
JI J. Am. Coll. Surg.
PD OCT
PY 2014
VL 219
IS 4
SU S
BP E10
EP E10
PG 1
WC Surgery
SC Surgery
GA CR1UU
UT WOS:000361111400021
ER
PT J
AU Oyetunji, SO
Xi, SC
Azoury, SC
Zhang, M
Hong, J
Inchauste, SM
Schrump, D
AF Oyetunji, Shakirat O.
Xi, Sichuan
Azoury, Said C.
Zhang, Mary
Hong, Julie
Inchauste, Suzanne M.
Schrump, David
TI Cigarette smoke induces epigenetic dysregulation of microrna expression
during esophageal adenocarcinogenesis
SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS
LA English
DT Meeting Abstract
CT 100th Annual Clinical Congress of the American-College-of-Surgeons
CY OCT 26-30, 2014
CL San Francisco, CA
SP Amer Coll Surg
C1 [Oyetunji, Shakirat O.; Xi, Sichuan; Azoury, Said C.; Zhang, Mary; Hong, Julie; Inchauste, Suzanne M.; Schrump, David] NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1072-7515
EI 1879-1190
J9 J AM COLL SURGEONS
JI J. Am. Coll. Surg.
PD OCT
PY 2014
VL 219
IS 4
SU S
BP E68
EP E68
PG 1
WC Surgery
SC Surgery
GA CR1UU
UT WOS:000361111400150
ER
PT J
AU Straughan, D
Neychev, VK
Sadowski, SM
Ellis, RJ
Patronas, N
Kebebew, E
Nilubol, N
AF Straughan, David
Neychev, Vladimir K.
Sadowski, Samira M.
Ellis, Ryan J.
Patronas, Nicholas
Kebebew, Electron
Nilubol, Naris
TI Do preoperative imaging features predict surgical complications of
carotid body tumors?
SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS
LA English
DT Meeting Abstract
CT 100th Annual Clinical Congress of the American-College-of-Surgeons
CY OCT 26-30, 2014
CL San Francisco, CA
SP Amer Coll Surg
C1 [Straughan, David; Neychev, Vladimir K.; Sadowski, Samira M.; Ellis, Ryan J.; Patronas, Nicholas; Kebebew, Electron; Nilubol, Naris] NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1072-7515
EI 1879-1190
J9 J AM COLL SURGEONS
JI J. Am. Coll. Surg.
PD OCT
PY 2014
VL 219
IS 4
SU S
BP E11
EP E11
PG 1
WC Surgery
SC Surgery
GA CR1UU
UT WOS:000361111400025
ER
PT J
AU Zhang, MR
Xi, SC
Oyetunji, S
Shukla, V
Rao, M
Hong, JL
Schrump, DS
AF Zhang, Mary R.
Xi, Sichuan
Oyetunji, Shakirat
Shukla, Vivek
Rao, Mahadev
Hong, Julie
Schrump, David S.
TI Mithramycin inhibits expression of the novel pluripotency factor
musashi-2 in lung cancer cells
SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS
LA English
DT Meeting Abstract
CT 100th Annual Clinical Congress of the American-College-of-Surgeons
CY OCT 26-30, 2014
CL San Francisco, CA
SP Amer Coll Surg
C1 [Zhang, Mary R.; Xi, Sichuan; Oyetunji, Shakirat; Shukla, Vivek; Rao, Mahadev; Hong, Julie; Schrump, David S.] NCI, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1072-7515
EI 1879-1190
J9 J AM COLL SURGEONS
JI J. Am. Coll. Surg.
PD OCT
PY 2014
VL 219
IS 4
SU S
BP E66
EP E67
PG 2
WC Surgery
SC Surgery
GA CR1UU
UT WOS:000361111400147
ER
PT J
AU Horinouchi, Y
Summers, FA
Ehrenshaft, M
Kawazoe, K
Tsuchiya, K
Tamaki, T
Mason, RP
AF Horinouchi, Yuya
Summers, Fiona A.
Ehrenshaft, Marilyn
Kawazoe, Kazuyoshi
Tsuchiya, Koichiro
Tamaki, Toshiaki
Mason, Ronald P.
TI Investigating free radical generation in HepG2 cells using immuno-spin
trapping
SO FREE RADICAL BIOLOGY AND MEDICINE
LA English
DT Meeting Abstract
C1 [Horinouchi, Yuya; Kawazoe, Kazuyoshi] Tokushima Univ Hosp Tokushima, Dept Pharm, Tokushima, Japan.
[Summers, Fiona A.; Ehrenshaft, Marilyn; Mason, Ronald P.] NIEHS, Natl Inst Hlth NC, Free Radical Metab Grp, Lab Toxicol & Pharmacol, Res Triangle Pk, NC 27709 USA.
[Tsuchiya, Koichiro] Univ Tokushima Grad Sch Tokushima, Inst Hlth Biosci, Dept Med Pharmacol, Tokushima, Japan.
[Tamaki, Toshiaki] Univ Tokushima Grad Sch Tokushima, Inst Hlth Biosci, Dept Pharmacol, Tokushima, Japan.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0891-5849
EI 1873-4596
J9 FREE RADICAL BIO MED
JI Free Radic. Biol. Med.
PD OCT
PY 2014
VL 75
SU 1
MA P36
BP S33
EP S33
DI 10.1016/j.freeradbiomed.2014.10.768
PG 1
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA CO9TV
UT WOS:000359519800090
PM 26461344
ER
PT J
AU Alonso, A
Yin, XY
Roetker, NS
Magnani, JW
Kronmal, RA
Ellinor, PT
Chen, LY
Lubitz, SA
McClelland, RL
McManus, DD
Soliman, EZ
Huxley, RR
Nazarian, S
Szklo, M
Heckbert, SR
Benjamin, EJ
AF Alonso, Alvaro
Yin, Xiaoyan
Roetker, Nicholas S.
Magnani, Jared W.
Kronmal, Richard A.
Ellinor, Patrick T.
Chen, Lin Y.
Lubitz, Steven A.
McClelland, Robyn L.
McManus, David D.
Soliman, Elsayed Z.
Huxley, Rachel R.
Nazarian, Saman
Szklo, Moyses
Heckbert, Susan R.
Benjamin, Emelia J.
TI Blood Lipids and the Incidence of Atrial Fibrillation: The Multi-Ethnic
Study of Atherosclerosis and the Framingham Heart Study
SO JOURNAL OF THE AMERICAN HEART ASSOCIATION
LA English
DT Article
DE atrial fibrillation; cholesterol; epidemiology; lipids; risk factors
ID DENSITY-LIPOPROTEIN CHOLESTEROL; RANDOMIZED CONTROLLED-TRIALS; NIIGATA
PREVENTIVE MEDICINE; RISK-FACTORS; NATRIURETIC PEPTIDE; METABOLIC
SYNDROME; SUBCLINICAL CVD; ASSOCIATION; DISEASE; ADULTS
AB Background-Dyslipidemia is a major contributor to the development of atherosclerosis and coronary disease. Its role in the etiology of atrial fibrillation (AF) is uncertain.
Methods and Results-We studied 7142 men and women from the Multi-Ethnic Study of Atherosclerosis (MESA) and the Framingham Heart Study who did not have prevalent AF at baseline and were not on lipid-lowering medications. Total cholesterol, high-density lipoprotein and low-density lipoprotein cholesterol, and triglycerides were measured using standard procedures. Incident AF during follow-up was identified from hospital discharge codes; review of medical charts; study electrocardiograms; and, in MESA only, Medicare claims. Multivariable Cox proportional hazards models were used to estimate hazard ratios and 95% confidence intervals of AF by clinical categories of blood lipids in each cohort. Study-specific results were meta-analyzed using inverse of variance weighting. During 9.6 years of mean follow-up, 480 AF cases were identified. In a combined analysis of multivariable-adjusted results from both cohorts, high levels of high-density lipoprotein cholesterol were associated with lower AF risk (hazard ratio 0.64, 95% CI 0.48 to 0.87 in those with levels >= 60 mg/dL versus <40 mg/dL), whereas high triglycerides were associated with higher risk of AF (hazard ratio 1.60, 95% CI 1.25 to 2.05 in those with levels >= 200 mg/dL versus <150 mg/dL). Total cholesterol and low-density lipoprotein cholesterol were not associated with the risk of AF.
Conclusion-In these 2 community-based cohorts, high-density lipoprotein cholesterol and triglycerides but not low-density lipoprotein cholesterol or total cholesterol were associated with the risk of AF, accounting for other cardiometabolic risk factors.
C1 [Alonso, Alvaro; Roetker, Nicholas S.] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN 55454 USA.
[Magnani, Jared W.; Benjamin, Emelia J.] Boston Univ, Sect Cardiovasc Med, Dept Med, Boston, MA 02215 USA.
[Yin, Xiaoyan] Boston Univ, Dept Biostat, Boston, MA 02215 USA.
[Yin, Xiaoyan; Magnani, Jared W.; McManus, David D.; Benjamin, Emelia J.] NHLBI, Framingham, MA USA.
[Yin, Xiaoyan; Magnani, Jared W.; McManus, David D.; Benjamin, Emelia J.] Boston Univ Framingham Heart Study, Framingham, MA USA.
[Kronmal, Richard A.; McClelland, Robyn L.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
[Heckbert, Susan R.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
[Ellinor, Patrick T.; Lubitz, Steven A.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA.
[Ellinor, Patrick T.; Lubitz, Steven A.] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA.
[Chen, Lin Y.] Univ Minnesota, Sch Med, Dept Med, Div Cardiovasc, Minneapolis, MN 55455 USA.
[McManus, David D.] Univ Massachusetts, Sch Med, Dept Med, Div Cardiol, Worcester, MA USA.
[Soliman, Elsayed Z.] Wake Forest Sch Med, Dept Epidemiol & Prevent, Epidemiol Cardiol Res Ctr, Winston Salem, NC USA.
[Huxley, Rachel R.] Univ Queensland, Sch Populat Hlth, Brisbane, Qld, Australia.
[Nazarian, Saman] Johns Hopkins Univ, Dept Med Cardiol, Baltimore, MD USA.
[Nazarian, Saman; Szklo, Moyses] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
[Benjamin, Emelia J.] Boston Univ, Dept Epidemiol, Sch Publ Hlth, Boston, MA USA.
RP Alonso, A (reprint author), Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, 1200 S 2nd St,Suite 300, Minneapolis, MN 55454 USA.
EM alonso@umn.edu
RI Huxley, Rachel/C-7032-2013; Huxley, Rachel/J-4638-2013; Alonso,
Alvaro/A-4917-2010;
OI Huxley, Rachel/0000-0002-2705-6616; Huxley, Rachel/0000-0002-2705-6616;
Alonso, Alvaro/0000-0002-2225-8323; Benjamin, Emelia/0000-0003-4076-2336
FU National Heart, Lung, and Blood Institute [N01-HC-95159, N01-HC-95160,
N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165,
N01-HC-95166, N01-HC-95167, N01-HC-95168, N01-HC-95169]; National Center
for Research Resources [UL1-TR-000040, UL1-RR-025005]; National
Institutes of Health [2R01HL092577, 1R01HL102214, 1RC1HL 101056,
6R01NS17950, K23HL114724, N01HC25195]
FX MESA: This research was supported by contracts N01-HC-95159,
N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164,
N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168 and N01-HC-95169
from the National Heart, Lung, and Blood Institute and by grants
UL1-TR-000040 and UL1-RR-025005 from the National Center for Research
Resources. FHS: This work was supported by grants 2R01HL092577,
1R01HL102214, 1RC1HL 101056, 6R01NS17950, K23HL114724, and N01HC25195
from the National Institutes of Health.
NR 38
TC 9
Z9 9
U1 0
U2 3
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 OCT
PY 2014
VL 3
IS 5
AR e001211
DI 10.1161/JAHA.114.001211
PG 20
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA CM0VL
UT WOS:000357396800028
PM 25292185
ER
PT J
AU Abaan, OD
Waterfall, J
Davis, S
Edelman, D
Gomez, A
Savage, S
Pommier, Y
Meltzer, P
AF Abaan, Ogan D.
Waterfall, Joshua
Davis, Sean
Edelman, Daniel
Gomez, Allison
Savage, Sharon
Pommier, Yves
Meltzer, Paul
TI Harvesting knowledge from unexploited genomic data: Estimating relative
telomere length from targeted-resequencing
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 105th Annual Meeting of the American-Association-for-Cancer-Research
(AACR)
CY APR 05-09, 2014
CL San Diego, CA
SP Amer Assoc Canc Res
C1 [Abaan, Ogan D.; Waterfall, Joshua; Davis, Sean; Edelman, Daniel; Gomez, Allison; Pommier, Yves; Meltzer, Paul] NCI CCR, Bethesda, MD USA.
[Savage, Sharon] NCI DCEG, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD OCT 1
PY 2014
VL 74
IS 19
SU S
MA 4167
DI 10.1158/1538-7445.AM2014-4167
PG 1
WC Oncology
SC Oncology
GA CB8VR
UT WOS:000349910202146
ER
PT J
AU Agrawal, L
Vaught, J
Moore, H
AF Agrawal, Lokesh
Vaught, Jim
Moore, Helen
TI Molecular biomarkers for cancer biospecimen integrity
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 105th Annual Meeting of the American-Association-for-Cancer-Research
(AACR)
CY APR 05-09, 2014
CL San Diego, CA
SP Amer Assoc Canc Res
C1 [Agrawal, Lokesh; Vaught, Jim; Moore, Helen] NCI, Rockville, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD OCT 1
PY 2014
VL 74
IS 19
SU S
MA 2493
DI 10.1158/1538-7445.AM2014-2493
PG 1
WC Oncology
SC Oncology
GA CB8UN
UT WOS:000349906903226
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PT J
AU Ahn, J
Ma, YF
Purdue, MP
Freedman, ND
Gapstur, SM
Yang, LY
Hayes, RB
Pei, ZH
AF Ahn, Jiyoung
Ma, Yingfei
Purdue, Mark P.
Freedman, Neal D.
Gapstur, Susan M.
Yang, Liying
Hayes, Richard B.
Pei, Zhiheng
TI Oral microbiome and risk of head and neck cancer, a nested case-control
study
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 105th Annual Meeting of the American-Association-for-Cancer-Research
(AACR)
CY APR 05-09, 2014
CL San Diego, CA
SP Amer Assoc Canc Res
C1 [Ahn, Jiyoung; Ma, Yingfei; Yang, Liying; Hayes, Richard B.] New York Univ Sch Med, New York, NY USA.
[Purdue, Mark P.; Freedman, Neal D.] NCI, DCEG, NIH, Bethesda, MD 20892 USA.
[Gapstur, Susan M.] Amer Canc Soc, Atlanta, GA 30329 USA.
[Pei, Zhiheng] Vet Affairs New York Harbor Healthcare Syst, New York, NY USA.
RI Purdue, Mark/C-9228-2016;
OI Purdue, Mark/0000-0003-1177-3108; Yang, Liying/0000-0003-1442-4915; Pei,
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J9 CANCER RES
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PD OCT 1
PY 2014
VL 74
IS 19
SU S
MA 4143
DI 10.1158/1538-7445.AM2014-4143
PG 1
WC Oncology
SC Oncology
GA CB8VR
UT WOS:000349910202124
ER
PT J
AU Ahsan, S
Raabe, E
Haffner, MC
Nazarian, J
Warren, K
Ballester, L
Quezado, M
Eberhart, C
Rodriguez, FJ
AF Ahsan, Sama
Raabe, Eric
Haffner, Michael C.
Nazarian, Javad
Warren, Katherine
Ballester, Leo
Quezado, Martha
Eberhart, Charles
Rodriguez, Fausto J.
TI Epigenetic derangements in histone and cytosine methylation are unique
to diffuse intrinsic pontine glioma (DIPG)
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 105th Annual Meeting of the American-Association-for-Cancer-Research
(AACR)
CY APR 05-09, 2014
CL San Diego, CA
SP Amer Assoc Canc Res
C1 [Ahsan, Sama; Raabe, Eric; Haffner, Michael C.; Eberhart, Charles; Rodriguez, Fausto J.] Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA.
[Nazarian, Javad] Childrens Natl Med Ctr, Washington Dc, DC USA.
[Warren, Katherine; Ballester, Leo; Quezado, Martha] NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
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PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD OCT 1
PY 2014
VL 74
IS 19
SU S
MA 384
DI 10.1158/1538-7445.AM2014-384
PG 2
WC Oncology
SC Oncology
GA CB8UN
UT WOS:000349906904351
ER
PT J
AU Alamri, AM
Groeneveld, S
Kang, K
Dabydeen, S
Wang, WS
Hennighausen, L
Kallakury, B
Liu, XF
Furth, PA
AF Alamri, Ahmad M.
Groeneveld, Svenja
Kang, Keunsoo
Dabydeen, Sarah
Wang, Weisheng
Hennighausen, Lothar
Kallakury, Bhaskar
Liu, Xuefeng
Furth, Priscilla A.
TI Characterizing growth features, allograft generation and transcriptomes
of cultured conditionally reprogrammed cells (CRC) prepared from primary
triple negative cancer from Brca1-mutant mice
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 105th Annual Meeting of the American-Association-for-Cancer-Research
(AACR)
CY APR 05-09, 2014
CL San Diego, CA
SP Amer Assoc Canc Res
C1 [Alamri, Ahmad M.; Dabydeen, Sarah; Wang, Weisheng; Kallakury, Bhaskar; Liu, Xuefeng; Furth, Priscilla A.] Georgetown Univ, Washington, DC USA.
[Groeneveld, Svenja] Univ Munich, Munich, Germany.
[Kang, Keunsoo; Hennighausen, Lothar] NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
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EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD OCT 1
PY 2014
VL 74
IS 19
SU S
MA 3918
DI 10.1158/1538-7445.AM2014-3918
PG 1
WC Oncology
SC Oncology
GA CB8VR
UT WOS:000349910201404
ER
PT J
AU Alewine, C
Maon-Osann, E
Pastan, I
AF Alewine, Christine
Maon-Osann, Emily
Pastan, Ira
TI Activity of mesothelin-targeted immunotoxin RG7787 against
triple-negative breast cancer
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 105th Annual Meeting of the American-Association-for-Cancer-Research
(AACR)
CY APR 05-09, 2014
CL San Diego, CA
SP Amer Assoc Canc Res
C1 [Alewine, Christine; Maon-Osann, Emily; Pastan, Ira] NCI, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 3
U2 6
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD OCT 1
PY 2014
VL 74
IS 19
SU S
MA 5440
DI 10.1158/1538-7445.AM2014-5440
PG 1
WC Oncology
SC Oncology
GA CB8VR
UT WOS:000349910204357
ER
PT J
AU Ali-Rahmani, F
Fitzgerald, D
Martin, S
Patel, P
Thomas, C
Pastan, I
AF Ali-Rahmani, Fatima
Fitzgerald, David
Martin, Scott
Patel, Paresma
Thomas, Craig
Pastan, Ira
TI Inhibition of collagen receptor discoidin domain receptor-1 (DDR1)
tyrosine kinase enhances cytotoxicity of anti-mesothelin immunotoxin
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 105th Annual Meeting of the American-Association-for-Cancer-Research
(AACR)
CY APR 05-09, 2014
CL San Diego, CA
SP Amer Assoc Canc Res
C1 [Ali-Rahmani, Fatima; Fitzgerald, David; Patel, Paresma; Pastan, Ira] NCI, NIH, Bethesda, MD 20892 USA.
[Martin, Scott; Thomas, Craig] NIH, Natl Ctr Adv Translat Sci, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 2
U2 2
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD OCT 1
PY 2014
VL 74
IS 19
SU S
MA 5428
DI 10.1158/1538-7445.AM2014-5428
PG 1
WC Oncology
SC Oncology
GA CB8VR
UT WOS:000349910204346
ER
PT J
AU Anderson, WF
Rosenberg, PS
Prat, A
Perou, CM
Sherman, ME
AF Anderson, William F.
Rosenberg, Philip S.
Prat, Aleix
Perou, Charles M.
Sherman, Mark E.
TI How many epidemiological types of breast cancer: Two, three, four, or
more
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 105th Annual Meeting of the American-Association-for-Cancer-Research
(AACR)
CY APR 05-09, 2014
CL San Diego, CA
SP Amer Assoc Canc Res
C1 [Anderson, William F.; Rosenberg, Philip S.; Sherman, Mark E.] NCI, Bethesda, MD 20892 USA.
[Prat, Aleix] Vall Hebron Inst Oncol, Barcelona, Spain.
[Perou, Charles M.] Univ N Carolina, Chapel Hill, NC USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD OCT 1
PY 2014
VL 74
IS 19
SU S
MA 266
DI 10.1158/1538-7445.AM2014-266
PG 1
WC Oncology
SC Oncology
GA CB8UN
UT WOS:000349906903407
ER
PT J
AU Anic, GM
Weinstein, SJ
Mannisto, S
Albanes, D
AF Anic, Gabriella M.
Weinstein, Stephanie J.
Mannisto, Satu
Albanes, Demetrius
TI Serum 25-hydroxyvitamin D, vitamin D binding protein, and lung cancer
survival in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 105th Annual Meeting of the American-Association-for-Cancer-Research
(AACR)
CY APR 05-09, 2014
CL San Diego, CA
SP Amer Assoc Canc Res
C1 [Anic, Gabriella M.; Weinstein, Stephanie J.; Albanes, Demetrius] NCI, Rockville, MD USA.
[Mannisto, Satu] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
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EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD OCT 1
PY 2014
VL 74
IS 19
SU S
MA 2180
DI 10.1158/1538-7445.AM2014-2180
PG 2
WC Oncology
SC Oncology
GA CB8UN
UT WOS:000349906902391
ER
PT J
AU Antignani, A
Pasetto, M
Choo, C
Angelus, E
Mathews, L
Guha, R
Shinn, P
Ferrer, M
Thomas, CJ
Pastan, I
Fitzgerald, DJ
AF Antignani, Antonella
Pasetto, Matteo
Choo, Chris
Angelus, Evan
Mathews, Lesley
Guha, Rajarshi
Shinn, Paul
Ferrer, Marc
Thomas, Craig J.
Pastan, Ira
Fitzgerald, David J.
TI Everolimus enhances the cytotoxic action of the immunotoxin, HA22,
directed to CD22 on B-cell malignancies
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 105th Annual Meeting of the American-Association-for-Cancer-Research
(AACR)
CY APR 05-09, 2014
CL San Diego, CA
SP Amer Assoc Canc Res
C1 [Antignani, Antonella; Pasetto, Matteo; Choo, Chris; Angelus, Evan; Pastan, Ira; Fitzgerald, David J.] NCI, Bethesda, MD 20892 USA.
[Mathews, Lesley; Guha, Rajarshi; Shinn, Paul; Ferrer, Marc; Thomas, Craig J.] Natl Ctr Adv Translat Sci, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
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PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
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J9 CANCER RES
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PD OCT 1
PY 2014
VL 74
IS 19
SU S
MA 2907
DI 10.1158/1538-7445.AM2014-2907
PG 2
WC Oncology
SC Oncology
GA CB8UN
UT WOS:000349906904174
ER
PT J
AU Balamurugan, K
Summers, GH
Sharan, S
Sterneck, E
AF Balamurugan, Kuppusamy
Summers, Glenn H.
Sharan, Shikha
Sterneck, Esta
TI C/EBPdelta links hypoxia and inflammation to the promotion of tumor cell
stemness through inhibition of FBXW7: A molecular target for HDAC
inhibitor action
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 105th Annual Meeting of the American-Association-for-Cancer-Research
(AACR)
CY APR 05-09, 2014
CL San Diego, CA
SP Amer Assoc Canc Res
C1 [Balamurugan, Kuppusamy; Sharan, Shikha; Sterneck, Esta] NCI, Frederick, MD 21701 USA.
[Summers, Glenn H.] Frederick Natl Lab Canc Res, Frederick, MD USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD OCT 1
PY 2014
VL 74
IS 19
SU S
MA 1913
DI 10.1158/1538-7445.AM2014-1913
PG 2
WC Oncology
SC Oncology
GA CB8UN
UT WOS:000349906902129
ER
PT J
AU Balasubramanian, P
Wang, LH
Lawrence, SM
Navas, T
Kummar, S
Hollingshead, M
Owusu, F
Parchment, RE
Tomaszewski, JE
Doroshow, JH
Kinders, RJ
AF Balasubramanian, Priya
Wang, Lihua
Lawrence, Scott M.
Navas, Tony
Kummar, Shivaani
Hollingshead, Melinda
Owusu, Francis
Parchment, Ralph E.
Tomaszewski, Joseph E.
Doroshow, James H.
Kinders, Robert J.
TI Isolation and characterization of circulating tumor cells (CTCs) from
peripheral blood specimens of patients with advanced solid tumor
malignancies (using ApoStream (TM) instrumentation)
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 105th Annual Meeting of the American-Association-for-Cancer-Research
(AACR)
CY APR 05-09, 2014
CL San Diego, CA
SP Amer Assoc Canc Res
C1 [Balasubramanian, Priya; Wang, Lihua; Lawrence, Scott M.; Navas, Tony; Owusu, Francis; Parchment, Ralph E.; Kinders, Robert J.] Frederick Natl Lab Canc Res, Lab Human Toxicol & Pharmacol, Appl Dev Directorate, Leidos Biomed Res Inc, Frederick, MD USA.
[Kummar, Shivaani; Tomaszewski, Joseph E.; Doroshow, James H.] NCI, Div Canc Treatment & Diag, Bethesda, MD 20892 USA.
[Hollingshead, Melinda] NCI, Biol Testing Branch, Frederick, MD 21701 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD OCT 1
PY 2014
VL 74
IS 19
SU S
MA 3062
DI 10.1158/1538-7445.AM2014-3062
PG 1
WC Oncology
SC Oncology
GA CB8VR
UT WOS:000349910200069
ER
PT J
AU Banerjee, HN
Hyman, G
Rousch, J
Mangalik, V
Vann, D
Krauss, C
Sharpe, S
Klinkebiel, D
Mandal, S
Verma, M
AF Banerjee, Hirendra N.
Hyman, Gwyn
Rousch, Jeffrey
Mangalik, Vinod
Vann, Deidre
Krauss, Christopher
Sharpe, Sabrina
Klinkebiel, David
Mandal, Santosh
Verma, Mukesh
TI An epigenetic study of DNA methylation and histone modification of brain
cancer Glioblastoma multiforme
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 105th Annual Meeting of the American-Association-for-Cancer-Research
(AACR)
CY APR 05-09, 2014
CL San Diego, CA
SP Amer Assoc Canc Res
C1 [Banerjee, Hirendra N.; Hyman, Gwyn; Rousch, Jeffrey; Mangalik, Vinod; Vann, Deidre; Krauss, Christopher; Sharpe, Sabrina] Elizabeth City State Univ, Elizabeth City, NC USA.
[Klinkebiel, David] Univ Nebraska, Sch Med, Omaha, NE 68198 USA.
[Mandal, Santosh] Morgan State Univ, Baltimore, MD 21239 USA.
[Verma, Mukesh] NCI, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD OCT 1
PY 2014
VL 74
IS 19
SU S
MA 2299
DI 10.1158/1538-7445.AM2014-2299
PG 1
WC Oncology
SC Oncology
GA CB8UN
UT WOS:000349906903018
ER
PT J
AU Barry, KH
Moore, L
Sampson, J
Yan, LY
Meyer, A
Chung, CC
Yeager, M
Amundadottir, L
Berndt, SI
AF Barry, Kathryn Hughes
Moore, Lee
Sampson, Joshua
Yan, Liying
Meyer, Ann
Chung, Charles C.
Yeager, Meredith
Amundadottir, Laufey
Berndt, Sonja I.
TI DNA methylation patterns in peripheral blood and the relationship with
cancer susceptibility loci at chromosome 8q24
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 105th Annual Meeting of the American-Association-for-Cancer-Research
(AACR)
CY APR 05-09, 2014
CL San Diego, CA
SP Amer Assoc Canc Res
C1 [Barry, Kathryn Hughes; Moore, Lee; Sampson, Joshua; Chung, Charles C.; Yeager, Meredith; Amundadottir, Laufey; Berndt, Sonja I.] NCI DCEG, Bethesda, MD USA.
[Yan, Liying; Meyer, Ann] EpigenDx Inc, Hopkinton, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD OCT 1
PY 2014
VL 74
IS 19
SU S
MA 288
DI 10.1158/1538-7445.AM2014-288
PG 2
WC Oncology
SC Oncology
GA CB8UN
UT WOS:000349906904145
ER
PT J
AU Basalingappa, KM
Mehta, M
Griffith, JN
Muralidharan, R
Gorospe, M
Ramesh, R
Munshi, A
AF Basalingappa, Kanthesh M.
Mehta, Meghna
Griffith, James N.
Muralidharan, Ranganayaki
Gorospe, Myriam
Ramesh, Rajagopal
Munshi, Anupama
TI siRNA-mediated HuR silencing sensitizes triple-negative breast cancer
cells to radiation therapy
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 105th Annual Meeting of the American-Association-for-Cancer-Research
(AACR)
CY APR 05-09, 2014
CL San Diego, CA
SP Amer Assoc Canc Res
C1 [Basalingappa, Kanthesh M.; Mehta, Meghna; Griffith, James N.; Muralidharan, Ranganayaki; Ramesh, Rajagopal; Munshi, Anupama] Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA.
[Gorospe, Myriam] NIA, Genet Lab, NIH, Baltimore, MD 21224 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD OCT 1
PY 2014
VL 74
IS 19
SU S
MA 3943
DI 10.1158/1538-7445.AM2014-3943
PG 1
WC Oncology
SC Oncology
GA CB8VR
UT WOS:000349910201427
ER
PT J
AU Baskar, S
Zhu, ZY
Labitigan, RL
Ovanesian, M
Orentas, RJ
Li, SQ
Marielle, YE
Shern, J
Dimitrov, DS
Maris, J
Mackall, C
Javed, K
AF Baskar, Sivasubramanian
Zhu, Zhongyu
Labitigan, Ramon Lorenzo
Ovanesian, Michelle
Orentas, Rimas J.
Li, Samuel Q.
Marielle, Yohe E.
Shern, John
Dimitrov, Dimiter S.
Maris, John
Mackall, Crystal
Javed, Khan
TI Development and characterization of anti-FGFR4 monoclonal antibodies as
therapeutic agents for human rhabdomyosarcoma
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 105th Annual Meeting of the American-Association-for-Cancer-Research
(AACR)
CY APR 05-09, 2014
CL San Diego, CA
SP Amer Assoc Canc Res
C1 [Baskar, Sivasubramanian; Labitigan, Ramon Lorenzo; Ovanesian, Michelle; Orentas, Rimas J.; Li, Samuel Q.; Marielle, Yohe E.; Shern, John; Mackall, Crystal; Javed, Khan] NCI, Bethesda, MD 20892 USA.
[Zhu, Zhongyu; Dimitrov, Dimiter S.] NIH, Prot Interact Grp, Canc & Inflammat Program, Frederick, MD USA.
[Maris, John] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA.
NR 0
TC 0
Z9 0
U1 1
U2 3
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD OCT 1
PY 2014
VL 74
IS 19
SU S
MA 652
DI 10.1158/1538-7445.AM2014-652
PG 2
WC Oncology
SC Oncology
GA CB8UN
UT WOS:000349906905114
ER
PT J
AU Basu, N
Johnson, RA
Shi, Q
Nelson, GD
Cunningham, JM
Goldberg, RM
Sinicrope, FA
Sargent, DJ
Alberts, SR
Petersen, GM
Thibodeau, SN
Skinner, HG
Litzelman, K
Seo, S
Vanderboom, RJ
Gangnon, RE
Engelman, CD
Rider, DN
Boardman, LA
AF Basu, Nivedita
Johnson, Ruth A.
Shi, Qian
Nelson, Garth D.
Cunningham, Julie M.
Goldberg, Richard M.
Sinicrope, Frank A.
Sargent, Daniel J.
Alberts, Steven R.
Petersen, Gloria M.
Thibodeau, Stephen N.
Skinner, Halcyon G.
Litzelman, Kristin
Seo, Songwon
Vanderboom, Russell J.
Gangnon, Ronald E.
Engelman, Corinne D.
Rider, David N.
Boardman, Lisa A.
TI Telomeres and survival in stage III colon cancers: Findings from NCCTG
N0147 (Alliance) study
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 105th Annual Meeting of the American-Association-for-Cancer-Research
(AACR)
CY APR 05-09, 2014
CL San Diego, CA
SP Amer Assoc Canc Res
C1 [Basu, Nivedita] Case Western Reserve Univ, Sch Med, Cleveland, OH USA.
[Johnson, Ruth A.; Shi, Qian; Nelson, Garth D.; Cunningham, Julie M.; Sinicrope, Frank A.; Sargent, Daniel J.; Alberts, Steven R.; Petersen, Gloria M.; Thibodeau, Stephen N.; Vanderboom, Russell J.; Rider, David N.; Boardman, Lisa A.] Mayo Clin, Rochester, MN USA.
[Goldberg, Richard M.] Ohio State Univ, Sch Med, Columbus, OH 43210 USA.
[Skinner, Halcyon G.; Seo, Songwon; Gangnon, Ronald E.; Engelman, Corinne D.] Univ Wisconsin, Madison, WI USA.
[Litzelman, Kristin] NCI, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD OCT 1
PY 2014
VL 74
IS 19
SU S
MA 5102
DI 10.1158/1538-7445.AM2014-5102
PG 1
WC Oncology
SC Oncology
GA CB8VR
UT WOS:000349910204056
ER
PT J
AU Bates, SE
Luchenko, V
Basseville, A
Bahr, J
Chakraborty, AR
McDonald, A
Zimmer, A
Piekarz, RL
Robey, RW
AF Bates, Susan E.
Luchenko, Victoria
Basseville, Agnes
Bahr, Julian
Chakraborty, Arup R.
McDonald, Andrew
Zimmer, Alexandra
Piekarz, Richard L.
Robey, Robert W.
TI Short-term romidepsin treatment combined with MAPK pathway inhibition
results in decreased mitochondrial hexokinase 2, increased mitochondrial
Bim and apoptosis in BRAF mutant cancers
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 105th Annual Meeting of the American-Association-for-Cancer-Research
(AACR)
CY APR 05-09, 2014
CL San Diego, CA
SP Amer Assoc Canc Res
C1 [Bates, Susan E.; Luchenko, Victoria; Basseville, Agnes; Bahr, Julian; Chakraborty, Arup R.; McDonald, Andrew; Zimmer, Alexandra; Robey, Robert W.] NCI, CCR, Bethesda, MD 20892 USA.
[Piekarz, Richard L.] NCI, DCTD, CTEP, IDB, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD OCT 1
PY 2014
VL 74
IS 19
SU S
MA 5536
DI 10.1158/1538-7445.AM2014-5536
PG 1
WC Oncology
SC Oncology
GA CB8VR
UT WOS:000349910204452
ER
PT J
AU Berny-Lang, MA
Greenspan, EJ
AF Berny-Lang, Michelle A.
Greenspan, Emily J.
TI NCI's Provocative Questions Initiative
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 105th Annual Meeting of the American-Association-for-Cancer-Research
(AACR)
CY APR 05-09, 2014
CL San Diego, CA
SP Amer Assoc Canc Res
C1 [Berny-Lang, Michelle A.; Greenspan, Emily J.] NCI, Ctr Strateg Sci Initiat, Off Director, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD OCT 1
PY 2014
VL 74
IS 19
SU S
MA 3500
DI 10.1158/1538-7445.AM2014-3500
PG 1
WC Oncology
SC Oncology
GA CB8VR
UT WOS:000349910200497
ER
PT J
AU Beumer, JH
Holleran, J
Doroshow, J
Chen, A
Allen, D
Covey, J
Tomaszewski, J
Pommier, Y
Kumar, S
Eiseman, JL
AF Beumer, Jan H.
Holleran, Julianne
Doroshow, James
Chen, Alice
Allen, Deborah
Covey, Joseph
Tomaszewski, Joseph
Pommier, Yves
Kumar, Shivaani
Eiseman, Julie L.
TI Phase I pharmacokinetics and pharmacodynamics of a novel
indenoisoquinoline topoisomerase 1 (TOP1) inhibitor, LMP400,
administered on a daily x 5 schedule
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 105th Annual Meeting of the American-Association-for-Cancer-Research
(AACR)
CY APR 05-09, 2014
CL San Diego, CA
SP Amer Assoc Canc Res
C1 [Beumer, Jan H.; Holleran, Julianne; Eiseman, Julie L.] Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA.
[Doroshow, James; Chen, Alice; Allen, Deborah; Covey, Joseph; Tomaszewski, Joseph; Pommier, Yves; Kumar, Shivaani] NCI, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 1
U2 2
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD OCT 1
PY 2014
VL 74
IS 19
SU S
MA 4643
DI 10.1158/1538-7445.AM2014-4643
PG 2
WC Oncology
SC Oncology
GA CB8VR
UT WOS:000349910203117
ER
PT J
AU Bian, YS
Han, JW
Kannabiran, V
Mohan, S
Friedman, J
Anderes, K
Chen, Z
Van Waes, C
AF Bian, Yansong
Han, Jiawei
Kannabiran, Vishnu
Mohan, Suresh
Friedman, Jay
Anderes, Kenna
Chen, Zhong
Van Waes, Carter
TI CK2 inhibitor CX-4945 modulates AKT, NF-kB, TP53 and MEK inhibitor
PD-325901 targets AP1 mediated CK2 inhibitor drug resistance in head and
neck cancer
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 105th Annual Meeting of the American-Association-for-Cancer-Research
(AACR)
CY APR 05-09, 2014
CL San Diego, CA
SP Amer Assoc Canc Res
C1 [Bian, Yansong; Han, Jiawei; Kannabiran, Vishnu; Mohan, Suresh; Friedman, Jay; Chen, Zhong; Van Waes, Carter] NIDCD, NIH, Bethesda, MD USA.
[Anderes, Kenna] Cylene Pharmaceut Inc, San Diego, CA USA.
NR 0
TC 1
Z9 1
U1 2
U2 2
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD OCT 1
PY 2014
VL 74
IS 19
SU S
MA 2687
DI 10.1158/1538-7445.AM2014-2687
PG 1
WC Oncology
SC Oncology
GA CB8UN
UT WOS:000349906903437
ER
PT J
AU Bodogai, M
Chang, CL
Biragyn, A
AF Bodogai, Monica
Chang, Catalina Lee
Biragyn, Arya
TI Myeloid-derived suppressive cells require education from tumor-evoked
Bregs to mediate metastasis
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 105th Annual Meeting of the American-Association-for-Cancer-Research
(AACR)
CY APR 05-09, 2014
CL San Diego, CA
SP Amer Assoc Canc Res
C1 [Bodogai, Monica; Chang, Catalina Lee; Biragyn, Arya] NIA, NIH, Baltimore, MD 21224 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD OCT 1
PY 2014
VL 74
IS 19
SU S
MA 3671
DI 10.1158/1538-7445.AM2014-3671
PG 1
WC Oncology
SC Oncology
GA CB8VR
UT WOS:000349910201163
ER
PT J
AU Boikos, SA
Xekouki, P
Faucz, FR
Pacak, K
Raygada, M
Adams, K
Szarek, E
Ball, E
Kim, SY
Fumagalli, E
Helman, LJ
Carney, JA
Stratakis, CA
AF Boikos, Sosipatros A.
Xekouki, Paraskevi
Faucz, Fabio R.
Pacak, Karel
Raygada, Margarita
Adams, Karen
Szarek, Evan
Ball, Evan
Kim, Su Young
Fumagalli, Elena
Helman, Lee J.
Carney, J. Aidan
Stratakis, Constantine A.
TI Few Carney's Triad patients have mutations in two subunits of the
succinate dehydrogenase enzyme (SDHB, SDHC)
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 105th Annual Meeting of the American-Association-for-Cancer-Research
(AACR)
CY APR 05-09, 2014
CL San Diego, CA
SP Amer Assoc Canc Res
C1 [Boikos, Sosipatros A.] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD USA.
[Xekouki, Paraskevi; Faucz, Fabio R.; Pacak, Karel; Raygada, Margarita; Adams, Karen; Szarek, Evan; Ball, Evan; Stratakis, Constantine A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
[Kim, Su Young; Helman, Lee J.] NCI, NIH, Bethesda, MD 20892 USA.
[Fumagalli, Elena] Inst Nazl Tumori, Canc Med Dept, Milan, Italy.
[Carney, J. Aidan] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA.
NR 0
TC 0
Z9 0
U1 1
U2 2
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD OCT 1
PY 2014
VL 74
IS 19
SU S
MA 568
DI 10.1158/1538-7445.AM2014-568
PG 1
WC Oncology
SC Oncology
GA CB8UN
UT WOS:000349906905032
ER
PT J
AU Boufraqech, M
Nilubol, N
Zhang, L
Sadowski, S
Gara, SK
He, M
Davis, S
Quezado, M
Kebebew, E
AF Boufraqech, Myriem
Nilubol, Naris
Zhang, Lisa
Sadowski, Samira
Gara, Sudheer Kumar
He, Mei
Davis, Sean
Quezado, Martha
Kebebew, Electron
TI Tumor suppressor miR-30a inhibits LOX expression and progression in
anaplastic thyroid cancer
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 105th Annual Meeting of the American-Association-for-Cancer-Research
(AACR)
CY APR 05-09, 2014
CL San Diego, CA
SP Amer Assoc Canc Res
C1 [Boufraqech, Myriem; Nilubol, Naris; Zhang, Lisa; Sadowski, Samira; Gara, Sudheer Kumar; He, Mei; Kebebew, Electron] NCI, Endocrine Oncol Branch, NIH, Bethesda, MD 20892 USA.
[Davis, Sean] NCI, CCR, CGB, Bethesda, MD 20892 USA.
[Quezado, Martha] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA.
RI Boufraqech, Myriem/E-4823-2016; Gara, Sudheer Kumar/E-8084-2016
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD OCT 1
PY 2014
VL 74
IS 19
SU S
MA 4367
DI 10.1158/1538-7445.AM2014-4367
PG 1
WC Oncology
SC Oncology
GA CB8VR
UT WOS:000349910202343
ER
PT J
AU Burman, B
Zhang, ZZ
Burgess, R
Roukos, V
Lieb, J
Misteli, T
AF Burman, Bharat
Zhang, Zhuzhu
Burgess, Rebecca
Roukos, Vassilis
Lieb, Jason
Misteli, Tom
TI Epigenetics of chromosomal breakage sites and translocations
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 105th Annual Meeting of the American-Association-for-Cancer-Research
(AACR)
CY APR 05-09, 2014
CL San Diego, CA
SP Amer Assoc Canc Res
C1 [Burman, Bharat] Tufts Univ, Sch Med, Boston, MA 02111 USA.
[Zhang, Zhuzhu] Univ N Carolina, Chapel Hill, NC USA.
[Burgess, Rebecca; Roukos, Vassilis; Misteli, Tom] NCI, Bethesda, MD 20892 USA.
[Lieb, Jason] Princeton Univ, Princeton, NJ 08544 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD OCT 1
PY 2014
VL 74
IS 19
SU S
MA 2406
DI 10.1158/1538-7445.AM2014-2406
PG 1
WC Oncology
SC Oncology
GA CB8UN
UT WOS:000349906903133
ER
PT J
AU Byrd, T
Fousek, K
Grada, Z
Aviles-Padilla, K
Bielamowicz, K
Gottschalk, S
Croix, BS
Fletcher, B
Hegde, M
Ahmed, N
AF Byrd, Tiara
Fousek, Kristen
Grada, Zakaria
Aviles-Padilla, Kevin
Bielamowicz, Kevin
Gottschalk, Stephen
Croix, Bradley S.
Fletcher, Bradley
Hegde, Meenakshi
Ahmed, Nabil
TI Two is better than one: Adoptive T cell therapy targeting tumor antigens
and the tumor endothelium potentiates T cell activation and cytolytic
activity
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 105th Annual Meeting of the American-Association-for-Cancer-Research
(AACR)
CY APR 05-09, 2014
CL San Diego, CA
SP Amer Assoc Canc Res
C1 [Byrd, Tiara; Fousek, Kristen; Grada, Zakaria; Aviles-Padilla, Kevin; Bielamowicz, Kevin; Gottschalk, Stephen; Hegde, Meenakshi; Ahmed, Nabil] Baylor Coll Med, Houston, TX 77030 USA.
[Croix, Bradley S.] Natl Canc Inst, Frederick, MD USA.
[Fletcher, Bradley] Univ Florida, Gainesville, FL USA.
RI Grada , Zakaria /B-9760-2016
NR 0
TC 0
Z9 0
U1 3
U2 5
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD OCT 1
PY 2014
VL 74
IS 19
SU S
MA LB-264
DI 10.1158/1538-7445.AM2014-LB-264
PG 2
WC Oncology
SC Oncology
GA CB8VR
UT WOS:000349910205295
ER
PT J
AU Camargo, MC
Michel, A
Kim, KM
Matsuo, K
Liao, LM
Torres, J
Zabaleta, J
Gulley, ML
Yatabe, Y
Alvarado-Cabrero, I
Lissowska, J
Kim, S
Pawlita, M
Rabkin, CS
AF Camargo, M. Constanza
Michel, Angelika
Kim, Kyoung-Mee
Matsuo, Keitaro
Liao, Linda M.
Torres, Javier
Zabaleta, Jovanny
Gulley, Margaret L.
Yatabe, Yasushi
Alvarado-Cabrero, Isabel
Lissowska, Jolanta
Kim, Sung
Pawlita, Michael
Rabkin, Charles S.
TI Multiplex Epstein-Barr virus (EBV) serology in EBV-positive and
-negative gastric cancer
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 105th Annual Meeting of the American-Association-for-Cancer-Research
(AACR)
CY APR 05-09, 2014
CL San Diego, CA
SP Amer Assoc Canc Res
C1 [Camargo, M. Constanza; Torres, Javier; Rabkin, Charles S.] NCI, Bethesda, MD 20892 USA.
[Michel, Angelika; Pawlita, Michael] German Canc Res Ctr, Heidelberg, Germany.
[Kim, Kyoung-Mee; Kim, Sung] Sungkyunkwan Univ, Sch Med, Seoul, South Korea.
[Matsuo, Keitaro] Kyushu Univ, Fac Med Sci, Fukuoka 812, Japan.
[Torres, Javier; Alvarado-Cabrero, Isabel] Inst Mexicano Seguro Social, Mexico City, DF, Mexico.
[Zabaleta, Jovanny] Louisiana State Univ, Hlth Sci Ctr, New Orleans, LA USA.
[Gulley, Margaret L.] Univ N Carolina, Chapel Hill, NC USA.
[Yatabe, Yasushi] Aichi Canc Ctr Hosp, Nagoya, Aichi 464, Japan.
[Lissowska, Jolanta] M Sklodowska Curie Mem Canc Ctr, Warsaw, Poland.
[Lissowska, Jolanta] Inst Oncol, Warsaw, Poland.
RI Camargo, M. Constanza/R-9891-2016; Waterboer, Tim/G-1252-2010
NR 0
TC 0
Z9 0
U1 0
U2 1
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD OCT 1
PY 2014
VL 74
IS 19
SU S
MA 277
DI 10.1158/1538-7445.AM2014-277
PG 2
WC Oncology
SC Oncology
GA CB8UN
UT WOS:000349906904026
ER
PT J
AU Carithers, L
Rao, A
Moore, H
AF Carithers, Latarsha
Rao, Abhi
Moore, Helen
TI Acquisition of biospecimens to support the Genotype-Tissue Expression
(GTEx) project
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 105th Annual Meeting of the American-Association-for-Cancer-Research
(AACR)
CY APR 05-09, 2014
CL San Diego, CA
SP Amer Assoc Canc Res
C1 [Carithers, Latarsha; Rao, Abhi; Moore, Helen] NCI, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD OCT 1
PY 2014
VL 74
IS 19
SU S
MA 2237
DI 10.1158/1538-7445.AM2014-2237
PG 2
WC Oncology
SC Oncology
GA CB8UN
UT WOS:000349906902448
ER
PT J
AU Carrick, DM
Mette, E
Hoyle, B
Rogers, SD
Gillanders, EM
Schully, SD
Mechanic, LE
AF Carrick, Danielle M.
Mette, Eliza
Hoyle, Brittany
Rogers, Scott D.
Gillanders, Elizabeth M.
Schully, Sheri D.
Mechanic, Leah E.
TI The use of biospecimens in cancer population science research
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 105th Annual Meeting of the American-Association-for-Cancer-Research
(AACR)
CY APR 05-09, 2014
CL San Diego, CA
SP Amer Assoc Canc Res
C1 [Carrick, Danielle M.; Mette, Eliza; Hoyle, Brittany; Rogers, Scott D.; Gillanders, Elizabeth M.; Schully, Sheri D.; Mechanic, Leah E.] NCI, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD OCT 1
PY 2014
VL 74
IS 19
SU S
MA 307
DI 10.1158/1538-7445.AM2014-307
PG 2
WC Oncology
SC Oncology
GA CB8UN
UT WOS:000349906904276
ER
PT J
AU Carrick, DM
Altekruse, S
Camalier, C
Cozen, W
Hernandez, B
Lynch, C
McGregor, P
Mehaffey, MG
McShane, L
Rohan, JP
Williams, M
Gillanders, EM
Mechanic, LE
Schully, S
AF Carrick, Danielle Mercatante
Altekruse, Sean
Camalier, Corrine
Cozen, Wendy
Hernandez, Brenda
Lynch, Charles
McGregor, Paul
Mehaffey, Michele G.
McShane, Lisa
Rohan, JoyAnn Phillips
Williams, Mickey
Gillanders, Elizabeth M.
Mechanic, Leah E.
Schully, Sheri
TI Feasibility study of next-generation sequencing on residual
formalin-fixed paraffin-embedded tissues
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 105th Annual Meeting of the American-Association-for-Cancer-Research
(AACR)
CY APR 05-09, 2014
CL San Diego, CA
SP Amer Assoc Canc Res
C1 [Carrick, Danielle Mercatante; Altekruse, Sean; McShane, Lisa; Gillanders, Elizabeth M.; Mechanic, Leah E.; Schully, Sheri] NCI, NIH, Rockville, MD USA.
[Camalier, Corrine; McGregor, Paul; Mehaffey, Michele G.; Rohan, JoyAnn Phillips; Williams, Mickey] Leidos Biomed Res Inc, Frederick, MD USA.
[Cozen, Wendy] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA.
[Hernandez, Brenda] Univ Hawaii, Ctr Canc, Honolulu, HI 96822 USA.
[Lynch, Charles] Univ Iowa, Iowa City, IA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD OCT 1
PY 2014
VL 74
IS 19
SU S
MA 304
DI 10.1158/1538-7445.AM2014-304
PG 2
WC Oncology
SC Oncology
GA CB8UN
UT WOS:000349906904273
ER
PT J
AU Cecchi, F
Lih, J
Lee, Y
Walsh, W
Williams, M
Bottaro, DP
AF Cecchi, Fabiola
Lih, Jason
Lee, Young
Walsh, William
Williams, Mickey
Bottaro, Donald P.
TI Gene expression array and pathway profiling analyses distinguish HGF/Met
pathways driving cell proliferation from invasion and identify events
correlated with prostate cancer progression
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 105th Annual Meeting of the American-Association-for-Cancer-Research
(AACR)
CY APR 05-09, 2014
CL San Diego, CA
SP Amer Assoc Canc Res
C1 [Cecchi, Fabiola; Lee, Young; Bottaro, Donald P.] NCI, Bethesda, MD 20892 USA.
[Lih, Jason; Walsh, William; Williams, Mickey] NCI, Frederick, MD 21701 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD OCT 1
PY 2014
VL 74
IS 19
SU S
MA 5259
DI 10.1158/1538-7445.AM2014-5259
PG 1
WC Oncology
SC Oncology
GA CB8VR
UT WOS:000349910204208
ER
PT J
AU Cerhan, JR
Berndt, SI
Vijai, J
Ghesquieres, H
McKay, J
Wang, SS
Wang, ZM
Yeager, M
Nieters, A
Cox, D
Monnereau, A
Flowers, C
De Roos, AJ
Brooks-Wilson, AR
Lan, Q
Severi, G
Melbye, M
Jackson, RD
Teras, LR
Purdue, M
Vajdic, C
Albanes, D
Bertrand, KA
Zeleniuch-Jacquotte, A
Crouch, S
Zhang, YW
Vineis, P
Slager, SL
Smedby, KE
Salles, G
Skibola, CF
Rothman, N
Chanock, SJ
AF Cerhan, James R.
Berndt, Sonja I.
Vijai, Joseph
Ghesquieres, Herve
McKay, James
Wang, Sophia S.
Wang, Zhaoming
Yeager, Meredith
Nieters, Alexandra
Cox, David
Monnereau, Alain
Flowers, Christopher
De Roos, Anneclaire J.
Brooks-Wilson, Angela R.
Lan, Qing
Severi, Gianluca
Melbye, Mads
Jackson, Rebecca D.
Teras, Lauren R.
Purdue, Mark
Vajdic, Claire
Albanes, Demetrius
Bertrand, Kimberly A.
Zeleniuch-Jacquotte, Anne
Crouch, Simon
Zhang, Yawei
Vineis, Paolo
Slager, Susan L.
Smedby, Karin E.
Salles, Gilles
Skibola, Christine F.
Rothman, Nathaniel
Chanock, Stephen J.
CA NHL GWAS Project
TI Genome-wide association study identifies multiple susceptibility loci
for diffuse large B-cell lymphoma
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 105th Annual Meeting of the American-Association-for-Cancer-Research
(AACR)
CY APR 05-09, 2014
CL San Diego, CA
SP Amer Assoc Canc Res
C1 [Cerhan, James R.; Slager, Susan L.] Mayo Clin, Coll Med, Rochester, MN USA.
[Berndt, Sonja I.; Wang, Zhaoming; Yeager, Meredith; Lan, Qing; Purdue, Mark; Albanes, Demetrius; Rothman, Nathaniel; Chanock, Stephen J.] NCI, Bethesda, MD 20892 USA.
[Vijai, Joseph] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
[Ghesquieres, Herve] Ctr Leon Berard, F-69373 Lyon, France.
[McKay, James] Int Agcy Res Canc, F-69372 Lyon, France.
[Wang, Sophia S.] City Hope Beckman Res Inst, Duarte, CA USA.
[Nieters, Alexandra] Ctr Chron Immunodeficiency, Freiburg, Germany.
[Cox, David] Canc Res Ctr Lyon, Lyon, France.
[Monnereau, Alain] Ctr Res Epidemiol & Populat Hlth CESP, Villejuif, France.
[Flowers, Christopher] Emory Univ, Sch Med, Atlanta, GA USA.
[De Roos, Anneclaire J.] Drexel Univ, Sch Publ Hlth, Philadelphia, PA 19104 USA.
[Brooks-Wilson, Angela R.; Lan, Qing] BC Canc Agcy, Vancouver, BC, Canada.
[Severi, Gianluca] Cancer Council Victoria, Melbourne, Vic, Australia.
[Melbye, Mads] Statens Serum Inst, DK-2300 Copenhagen, Denmark.
[Jackson, Rebecca D.] Ohio State Univ, Columbus, OH 43210 USA.
[Teras, Lauren R.] Amer Canc Soc, Atlanta, GA 30329 USA.
[Vajdic, Claire] Univ New S Wales, Sydney, NSW, Australia.
[Bertrand, Kimberly A.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
[Zeleniuch-Jacquotte, Anne] NYU, Sch Med, New York, NY USA.
[Crouch, Simon] Univ York, York YO10 5DD, N Yorkshire, England.
[Zhang, Yawei] Yale Univ, Sch Publ Hlth, New Haven, CT USA.
[Vineis, Paolo] Imperial Coll London, London, England.
[Smedby, Karin E.] Karolinska Inst, Stockholm, Sweden.
[Salles, Gilles] Hosp Civils Lyon, Lyon, France.
[Skibola, Christine F.] Univ Alabama Birmingham, Birmingham, AL USA.
RI Flowers, Christopher/F-1953-2010; Brooks-Wilson, Angela/E-9399-2012;
OI Flowers, Christopher/0000-0002-9524-3990; Brooks-Wilson,
Angela/0000-0003-1009-6408; Zeleniuch-Jacquotte,
Anne/0000-0001-9350-1303
NR 0
TC 0
Z9 0
U1 0
U2 2
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD OCT 1
PY 2014
VL 74
IS 19
SU S
MA LB-272
DI 10.1158/1538-7445.AM2014-LB-272
PG 2
WC Oncology
SC Oncology
GA CB8VR
UT WOS:000349910205303
ER
PT J
AU Chavan, TS
Jang, H
Khavrutskii, L
Freed, BC
Johannessen, L
Tarasov, SG
Abraham, SJ
Gaponenko, V
Nussinov, R
Tarasova, N
AF Chavan, Tanmay S.
Jang, Hyunbum
Khavrutskii, Lyuba
Freed, Benjamin C.
Johannessen, Liv
Tarasov, Sergey G.
Abraham, Sherwin J.
Gaponenko, Vadim
Nussinov, Ruth
Tarasova, Nadya
TI High affinity interaction of K-Ras4B hypervariable region with Ras
active site
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 105th Annual Meeting of the American-Association-for-Cancer-Research
(AACR)
CY APR 05-09, 2014
CL San Diego, CA
SP Amer Assoc Canc Res
C1 [Chavan, Tanmay S.; Abraham, Sherwin J.; Gaponenko, Vadim] Univ Illinois, Chicago, IL USA.
[Jang, Hyunbum; Khavrutskii, Lyuba; Freed, Benjamin C.; Johannessen, Liv; Tarasov, Sergey G.; Nussinov, Ruth; Tarasova, Nadya] NCI, Frederick, MD 21701 USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD OCT 1
PY 2014
VL 74
IS 19
SU S
MA 3224
DI 10.1158/1538-7445.AM2014-3224
PG 1
WC Oncology
SC Oncology
GA CB8VR
UT WOS:000349910200228
ER
PT J
AU Chen, J
Chen, JS
Gi, Y
Katz, LH
Shin, JH
Phan, L
Jogunoori, W
Shukla, V
Mishra, B
Li, SL
Javle, M
Hung, MC
Mishra, L
AF Chen, Jian
Chen, Jiun-Sheng
Gi, YoungJin
Katz, Lior H.
Shin, Ji-Hyun
Liem Phan
Jogunoori, Wilma
Shukla, Vivek
Mishra, Bibhuti
Li, Shulin
Javle, Milind
Hung, Mien-Chie
Mishra, Lopa
TI Targeting TGF-beta regulated E3 ligases: a novel therapeutic approach
for primary liver cancer
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 105th Annual Meeting of the American-Association-for-Cancer-Research
(AACR)
CY APR 05-09, 2014
CL San Diego, CA
SP Amer Assoc Canc Res
C1 [Chen, Jian; Chen, Jiun-Sheng; Gi, YoungJin; Katz, Lior H.; Shin, Ji-Hyun; Liem Phan; Li, Shulin; Javle, Milind; Hung, Mien-Chie; Mishra, Lopa] UT MD Anderson Canc Ctr, Houston, TX USA.
[Jogunoori, Wilma; Mishra, Bibhuti] Vet Affairs Med Ctr, Inst Clin Res, Washington, DC 20422 USA.
[Shukla, Vivek] NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD OCT 1
PY 2014
VL 74
IS 19
SU S
MA 2784
DI 10.1158/1538-7445.AM2014-2784
PG 2
WC Oncology
SC Oncology
GA CB8UN
UT WOS:000349906904042
ER
PT J
AU Chen, JQ
Kedei, N
Herrmann, MA
Blumberg, PM
AF Chen, Jin-Qiu
Kedei, Noemi
Herrmann, Michelle A.
Blumberg, Peter M.
TI Quantitative proteomic assessment of differential ligand responses
downstream of protein kinase C activation
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 105th Annual Meeting of the American-Association-for-Cancer-Research
(AACR)
CY APR 05-09, 2014
CL San Diego, CA
SP Amer Assoc Canc Res
C1 [Chen, Jin-Qiu; Kedei, Noemi; Herrmann, Michelle A.; Blumberg, Peter M.] NCI, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD OCT 1
PY 2014
VL 74
IS 19
SU S
MA 5315
DI 10.1158/1538-7445.AM2014-5315
PG 1
WC Oncology
SC Oncology
GA CB8VR
UT WOS:000349910204236
ER
PT J
AU Chen, J
Hackett, CS
Zhang, SL
Song, YK
Molinaro, A
Quigley, DA
Balmain, A
Gustafson, WC
Van Dyke, TA
Kwok, PY
Khan, J
Weiss, WA
AF Chen, Justin
Hackett, Christopher S.
Zhang, Shile
Song, Young K.
Molinaro, Annette
Quigley, David A.
Balmain, Allan
Gustafson, William C.
Van Dyke, Terry A.
Kwok, Pui-Yan
Khan, Javed
Weiss, William A.
TI A genetic analysis of splicing in neuroblastoma identifies opposing
functions for FUBP1 splice variants in MYC regulation
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 105th Annual Meeting of the American-Association-for-Cancer-Research
(AACR)
CY APR 05-09, 2014
CL San Diego, CA
SP Amer Assoc Canc Res
C1 [Chen, Justin; Hackett, Christopher S.; Molinaro, Annette; Quigley, David A.; Balmain, Allan; Gustafson, William C.; Kwok, Pui-Yan; Weiss, William A.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Zhang, Shile; Song, Young K.; Khan, Javed] NCI, Gaithersburg, MD USA.
[Van Dyke, Terry A.] NCI, Frederick, MD 21701 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD OCT 1
PY 2014
VL 74
IS 19
SU S
MA 3413
DI 10.1158/1538-7445.AM2014-3413
PG 1
WC Oncology
SC Oncology
GA CB8VR
UT WOS:000349910200412
ER
PT J
AU Cheng, H
Yang, XP
Si, H
Saleh, A
Coupar, J
Ferris, RL
Yarbrough, WG
Prince, ME
Carey, TE
Van Waes, C
Chen, Z
AF Cheng, Hui
Yang, Xinping
Si, Han
Saleh, Anthony
Coupar, Jamie
Ferris, Robert L.
Yarbrough, Wendell G.
Prince, Mark E.
Carey, Thomas E.
Van Waes, Carter
Chen, Zhong
TI Genomic exome DNA sequencing identifies top driver genetic alterations
in head and neck cancer cell lines of different HPV status
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 105th Annual Meeting of the American-Association-for-Cancer-Research
(AACR)
CY APR 05-09, 2014
CL San Diego, CA
SP Amer Assoc Canc Res
C1 [Cheng, Hui; Yang, Xinping; Si, Han; Saleh, Anthony; Coupar, Jamie; Van Waes, Carter; Chen, Zhong] Natl Inst Deafness & Other Commun Disorders, NIH, Bethesda, MD USA.
[Ferris, Robert L.] Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA.
[Yarbrough, Wendell G.] Yale Univ, Sch Med, Yale Canc Ctr, Smilow Canc Hosp, New Haven, CT USA.
[Prince, Mark E.; Carey, Thomas E.] Univ Michigan, Dept Otolaryngol Head & Neck Surg, Ann Arbor, MI 48109 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD OCT 1
PY 2014
VL 74
IS 19
SU S
MA 3434
DI 10.1158/1538-7445.AM2014-3434
PG 1
WC Oncology
SC Oncology
GA CB8VR
UT WOS:000349910200433
ER
PT J
AU Chiou, VL
Kohn, EC
Annunziata, CM
Minasian, L
Zujewski, J
Yu, MS
Ji, J
Doroshow, J
Gordon, N
Houston, N
Lee, JM
AF Chiou, Victoria L.
Kohn, Elise C.
Annunziata, Christina M.
Minasian, Lori
Zujewski, JoAnne
Yu, Minshu
Ji, Jay
Doroshow, James
Gordon, Nicolas
Houston, Nicole
Lee, Jung-Min
TI Phase I/Ib study of the PARP inhibitor (PARPi) olaparib (O) with
carboplatin (C) in triple negative breast cancer (TNBC) at low genetic
risk (NCT00647062)
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 105th Annual Meeting of the American-Association-for-Cancer-Research
(AACR)
CY APR 05-09, 2014
CL San Diego, CA
SP Amer Assoc Canc Res
C1 [Chiou, Victoria L.; Kohn, Elise C.; Annunziata, Christina M.; Minasian, Lori; Zujewski, JoAnne; Yu, Minshu; Gordon, Nicolas; Houston, Nicole; Lee, Jung-Min] Natl Canc Inst, Ctr Canc Res, Med Oncol Branch, Bethesda, MD USA.
[Ji, Jay; Doroshow, James] Natl Canc Inst, Div Canc Treatment & Diag, Bethesda, MD USA.
RI Annunziata, Christina/L-3219-2016
OI Annunziata, Christina/0000-0003-2033-6532
NR 0
TC 0
Z9 0
U1 1
U2 1
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD OCT 1
PY 2014
VL 74
IS 19
SU S
MA CT337
DI 10.1158/1538-7445.AM2014-CT337
PG 1
WC Oncology
SC Oncology
GA CB8VR
UT WOS:000349910205101
ER
PT J
AU Chowdhury, SA
Subramanian, A
Schaffer, AA
Shackney, SE
Wangsa, D
Heselmeyer-Haddad, K
Ried, T
Schwartz, R
AF Chowdhury, Salim A.
Subramanian, Ayshwarya
Schaeffer, Alejandro A.
Shackney, Stanley E.
Wangsa, Darawalee
Heselmeyer-Haddad, Kerstin
Ried, Thomas
Schwartz, Russell
TI Inferring evolutionary models of tumor progression from single-cell
heterogeneity data
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 105th Annual Meeting of the American-Association-for-Cancer-Research
(AACR)
CY APR 05-09, 2014
CL San Diego, CA
SP Amer Assoc Canc Res
C1 [Chowdhury, Salim A.; Subramanian, Ayshwarya; Schwartz, Russell] Carnegie Mellon Univ, Pittsburgh, PA 15213 USA.
[Schaeffer, Alejandro A.; Wangsa, Darawalee; Heselmeyer-Haddad, Kerstin; Ried, Thomas] NIH, Bethesda, MD 20892 USA.
[Shackney, Stanley E.] Intelligent Oncotherapeut, Pittsburgh, PA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD OCT 1
PY 2014
VL 74
IS 19
SU S
MA 5338
DI 10.1158/1538-7445.AM2014-5338
PG 1
WC Oncology
SC Oncology
GA CB8VR
UT WOS:000349910204257
ER
PT J
AU Chun, HJE
Zhu, K
Qian, JQ
Mungall, KL
Ma, Y
Zhao, YJ
Mungall, AJ
Moore, RA
Schein, JE
Gerhard, DS
Perlman, EJ
Marra, MA
AF Chun, Hye-Jung E.
Zhu, Kelsey
Qian, Jenny Q.
Mungall, Karen L.
Ma, Yussanne
Zhao, Yong-Jun
Mungall, Andrew J.
Moore, Richard A.
Schein, Jacquie E.
Gerhard, Daniela S.
Perlman, Elizabeth J.
Marra, Marco A.
TI Whole genome sequencing of rhabdoid tumors of the kidney
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 105th Annual Meeting of the American-Association-for-Cancer-Research
(AACR)
CY APR 05-09, 2014
CL San Diego, CA
SP Amer Assoc Canc Res
C1 [Chun, Hye-Jung E.; Marra, Marco A.] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada.
[Zhu, Kelsey; Qian, Jenny Q.; Mungall, Karen L.; Ma, Yussanne; Zhao, Yong-Jun; Mungall, Andrew J.; Moore, Richard A.; Schein, Jacquie E.] BC Canc Agcy, Canadas Michael Smith Genome Sci Ctr, Vancouver, BC, Canada.
[Gerhard, Daniela S.] NCI, Off Canc Genom, US NIH, Bethesda, MD 20892 USA.
[Perlman, Elizabeth J.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD OCT 1
PY 2014
VL 74
IS 19
SU S
MA 3087
DI 10.1158/1538-7445.AM2014-3087
PG 1
WC Oncology
SC Oncology
GA CB8VR
UT WOS:000349910200093
ER
PT J
AU Chung, E
Horton, J
White, A
Scroggins, B
Hudak, K
Citrin, D
AF Chung, Eunjoo
Horton, Jason
White, Ayla
Scroggins, Bradly
Hudak, Kathryn
Citrin, Deborah
TI Enhanced expression of secretory clusterin/apolipoprotein J (sCLU) in
pulmonary alveolar stem cells after ionizing radiation exposure
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 105th Annual Meeting of the American-Association-for-Cancer-Research
(AACR)
CY APR 05-09, 2014
CL San Diego, CA
SP Amer Assoc Canc Res
C1 [Chung, Eunjoo; Horton, Jason; White, Ayla; Scroggins, Bradly; Hudak, Kathryn; Citrin, Deborah] NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD OCT 1
PY 2014
VL 74
IS 19
SU S
MA 852
DI 10.1158/1538-7445.AM2014-852
PG 1
WC Oncology
SC Oncology
GA CB8UN
UT WOS:000349906905311
ER
PT J
AU Chung, S
Song, N
Sung, H
Park, SK
Han, W
Noh, DY
Ahn, SH
Yoo, KY
Kang, D
Choi, JY
AF Chung, Seokang
Song, Nan
Sung, Hyuna
Park, Sue K.
Han, Wonshik
Noh, Dong-Young
Ahn, Sei-Hyun
Yoo, Keun-Young
Kang, Daehee
Choi, Ji-Yeob
TI Genetic variation in obesity-related genes and breast cancer risk in the
Seoul Breast Cancer Study
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 105th Annual Meeting of the American-Association-for-Cancer-Research
(AACR)
CY APR 05-09, 2014
CL San Diego, CA
SP Amer Assoc Canc Res
C1 [Chung, Seokang; Park, Sue K.; Kang, Daehee; Choi, Ji-Yeob] Seoul Natl Univ Grad Sch, Dept Biomed Sci, Seoul, South Korea.
[Song, Nan] Seoul Natl Univ Grad Sch, Seoul, South Korea.
[Sung, Hyuna] NCI, Genet Epidemiol Branch, Div Epidemiol & Genet, Bethesda, MD 20892 USA.
[Han, Wonshik; Noh, Dong-Young] Seoul Natl Univ Grad Sch, Canc Res Inst, Seoul, South Korea.
[Ahn, Sei-Hyun] Univ Ulsan Coll Med, Dept Surg, Seoul, South Korea.
[Ahn, Sei-Hyun] ASAN Med Ctr, Seoul, South Korea.
[Yoo, Keun-Young] Seoul Natl Univ Coll Med, Dept Prevent Med, Seoul, South Korea.
RI Han, Wonshik/B-3699-2008
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD OCT 1
PY 2014
VL 74
IS 19
SU S
MA 3273
DI 10.1158/1538-7445.AM2014-3273
PG 1
WC Oncology
SC Oncology
GA CB8VR
UT WOS:000349910200273
ER
PT J
AU Comertpay, S
Mezzapelle, R
Tanji, M
Strianese, O
Pass, HI
Weigel, T
Friedberg, J
Sugarbaker, P
Krausz, T
Wang, E
Gaudino, G
Yang, HN
Powers, A
Parsons, B
Pastorino, S
Carbone, M
AF Comertpay, Sabahattin
Mezzapelle, Rosanna
Tanji, Mika
Strianese, Oriana
Pass, Harvey I.
Weigel, Tracey
Friedberg, Joseph
Sugarbaker, Paul
Krausz, Thomas
Wang, Ena
Gaudino, Giovanni
Yang, Haining
Powers, Amy
Parsons, Barbara
Pastorino, Sandra
Carbone, Michele
TI Evaluation of clonal origin of malignant mesothelioma/polyclonal origin
of malignant mesothelioma
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 105th Annual Meeting of the American-Association-for-Cancer-Research
(AACR)
CY APR 05-09, 2014
CL San Diego, CA
SP Amer Assoc Canc Res
C1 [Comertpay, Sabahattin; Tanji, Mika; Strianese, Oriana; Gaudino, Giovanni; Yang, Haining; Powers, Amy; Pastorino, Sandra; Carbone, Michele] Univ Hawaii, Ctr Canc, Honolulu, HI 96822 USA.
[Mezzapelle, Rosanna] Univ Piemonte Orientale Amedeo Avogadro, Novara, Italy.
[Pass, Harvey I.] NYU, NYU Langone Med Ctr, New York, NY USA.
[Weigel, Tracey] Univ Wisconsin, Dept Surg, Sch Med & Publ Hlth, Madison, WI USA.
[Friedberg, Joseph] Penn Presbyterian Med Ctr, Philadelphia, PA USA.
[Sugarbaker, Paul] MedStar Washington Hosp Ctr, Washington, DC USA.
[Krausz, Thomas] Univ Chicago, Chicago, IL 60637 USA.
[Wang, Ena] NIH, Bethesda, MD 20892 USA.
[Parsons, Barbara] Natl Ctr Toxicol Res, Jefferson, AR 72079 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD OCT 1
PY 2014
VL 74
IS 19
SU S
MA 3188
DI 10.1158/1538-7445.AM2014-3188
PG 1
WC Oncology
SC Oncology
GA CB8VR
UT WOS:000349910200192
ER
PT J
AU Cong, Y
Zhan, M
Wong, ST
AF Cong, Yang
Zhan, Ming
Wong, Stephen T.
TI Network-based identification of gene signatures of
epithelial-mesenchymal transition in breast cancer
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 105th Annual Meeting of the American-Association-for-Cancer-Research
(AACR)
CY APR 05-09, 2014
CL San Diego, CA
SP Amer Assoc Canc Res
C1 [Cong, Yang; Zhan, Ming; Wong, Stephen T.] Weill Cornell Med Coll, Houston Methodist Res Inst, Dept Syst Med & Bioengn, NCI Ctr Modeling Canc Dev, Houston, TX 77030 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD OCT 1
PY 2014
VL 74
IS 19
SU S
MA 3998
DI 10.1158/1538-7445.AM2014-3998
PG 1
WC Oncology
SC Oncology
GA CB8VR
UT WOS:000349910201482
ER
PT J
AU Conlon, KC
Lugli, E
Rosenberg, SA
Morris, JC
Fleisher, T
Welles, H
Dubois, S
Perera, L
Goldman, C
Bryant, B
Decker, J
Shih, J
Worthy, T
Figg, W
Peer, C
Sneller, M
Lane, HC
Yovandich, J
Creekmore, S
Roederer, M
Waldmann, TA
AF Conlon, Kevin C.
Lugli, Enrico
Rosenberg, Steven A.
Morris, John C.
Fleisher, Thomas
Welles, Hugh
Dubois, Sigrid
Perera, Liyanage
Goldman, Carolyn
Bryant, Bonita
Decker, Jean
Shih, Joanna
Worthy, Tat'Yana
Figg, William
Peer, Cody
Sneller, Michael
Lane, H. Clifford
Yovandich, Jason
Creekmore, Stephen
Roederer, Mario
Waldmann, Thomas A.
TI Results from the first-in-human phase I trials of recombinant human
Interleukin 15 (rhIL-15) administered as a daily 30 minute intravenous
infusion (IVB) for 12 consecutive days or as continuous intravenous
infusion (CIV) for 240 hours in patients with refractory metastatic
cancers
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 105th Annual Meeting of the American-Association-for-Cancer-Research
(AACR)
CY APR 05-09, 2014
CL San Diego, CA
SP Amer Assoc Canc Res
C1 [Conlon, Kevin C.; Morris, John C.; Dubois, Sigrid; Perera, Liyanage; Goldman, Carolyn; Bryant, Bonita; Decker, Jean; Worthy, Tat'Yana; Waldmann, Thomas A.] NCI, Metab Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Lugli, Enrico; Welles, Hugh; Roederer, Mario] NIAID, Immunotechnol Sect, Vaccine Res Ctr, Bethesda, MD 20892 USA.
[Rosenberg, Steven A.] NCI, Surg Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Morris, John C.] Univ Cincinnati, Inst Canc, Cincinnati, OH USA.
[Fleisher, Thomas] NIH, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA.
[Shih, Joanna] NCI, Biometr Res Branch, Bethesda, MD 20892 USA.
[Figg, William; Peer, Cody] NCI, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Sneller, Michael; Lane, H. Clifford] NIAID, Div Intramural Res, Bethesda, MD 20892 USA.
[Yovandich, Jason; Creekmore, Stephen] NCI, Biol Resources Branch, Div Canc Treatment & Diag, Bethesda, MD 20892 USA.
RI Figg Sr, William/M-2411-2016
NR 0
TC 0
Z9 0
U1 0
U2 2
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD OCT 1
PY 2014
VL 74
IS 19
SU S
MA 2575
DI 10.1158/1538-7445.AM2014-2575
PG 2
WC Oncology
SC Oncology
GA CB8UN
UT WOS:000349906903316
ER
PT J
AU Cook, MB
Wood, S
Cash, BD
Young, P
Acosta, RD
Falk, RT
Pfeiffer, R
Hu, N
Giffen, C
Turcotte, V
Caron, P
Guillemette, C
Dawsey, SM
Abnet, CC
Hyland, PL
Taylor, PR
AF Cook, Michael B.
Wood, Shannon
Cash, Brooks D.
Young, Patrick
Acosta, Ruben D.
Falk, Roni T.
Pfeiffer, Ruth
Hu, Nan
Giffen, Carol
Turcotte, Veronique
Caron, Patrick
Guillemette, Chantal
Dawsey, Sanford M.
Abnet, Christian C.
Hyland, Paula L.
Taylor, Philip R.
TI An analysis of circulating sex steroid hormones in relation to Barrett's
esophagus
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 105th Annual Meeting of the American-Association-for-Cancer-Research
(AACR)
CY APR 05-09, 2014
CL San Diego, CA
SP Amer Assoc Canc Res
C1 [Cook, Michael B.; Wood, Shannon; Falk, Roni T.; Pfeiffer, Ruth; Hu, Nan; Dawsey, Sanford M.; Abnet, Christian C.; Hyland, Paula L.; Taylor, Philip R.] NCI, Bethesda, MD 20892 USA.
[Cash, Brooks D.; Young, Patrick; Acosta, Ruben D.] Natl Naval Med Canc, Bethesda, MD USA.
[Giffen, Carol] IMS, Silver Spring, MD USA.
[Turcotte, Veronique; Caron, Patrick; Guillemette, Chantal] Univ Laval, Quebec City, PQ, Canada.
RI Abnet, Christian/C-4111-2015
OI Abnet, Christian/0000-0002-3008-7843
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD OCT 1
PY 2014
VL 74
IS 19
SU S
MA 2207
DI 10.1158/1538-7445.AM2014-2207
PG 2
WC Oncology
SC Oncology
GA CB8UN
UT WOS:000349906902418
ER
PT J
AU Coyne, GO
Jochems, C
Heery, C
Singh, H
Surolia, I
Riley, R
Madan, R
Dahut, W
Steinberg, S
Gulley, J
Schlom, J
AF Coyne, Geraldine O'Sullivan
Jochems, Caroline
Heery, Christopher
Singh, Harpreet
Surolia, Ira
Riley, Robin
Madan, Ravi
Dahut, William
Steinberg, Seth
Gulley, James
Schlom, Jeffrey
TI A combination trial of vaccine plus ipilimumab in metastatic
castration-resistant prostate cancer patients: Immune correlates
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 105th Annual Meeting of the American-Association-for-Cancer-Research
(AACR)
CY APR 05-09, 2014
CL San Diego, CA
SP Amer Assoc Canc Res
C1 [Coyne, Geraldine O'Sullivan; Jochems, Caroline; Heery, Christopher; Singh, Harpreet; Surolia, Ira; Riley, Robin; Madan, Ravi; Dahut, William; Steinberg, Seth; Gulley, James; Schlom, Jeffrey] NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD OCT 1
PY 2014
VL 74
IS 19
SU S
MA 5012
DI 10.1158/1538-7445.AM2014-5012
PG 2
WC Oncology
SC Oncology
GA CB8VR
UT WOS:000349910203471
ER
PT J
AU Curiel-Lewandrowski, C
Tang, J
Einspahr, J
Bermudez, Y
Hsu, CH
Rezaee, M
Lee, A
Tangrea, J
Parnes, H
Alberts, D
Chow, HHS
AF Curiel-Lewandrowski, Clara
Tang, Jean
Einspahr, Janine
Bermudez, Yira
Hsu, Chiu-Hsieh
Rezaee, Melika
Lee, Alex
Tangrea, Joe
Parnes, Howard
Alberts, David
Chow, H-H. Sherry
TI Pilot study on the bioactivity of vitamin D in the skin after oral
supplementation
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 105th Annual Meeting of the American-Association-for-Cancer-Research
(AACR)
CY APR 05-09, 2014
CL San Diego, CA
SP Amer Assoc Canc Res
C1 [Curiel-Lewandrowski, Clara; Einspahr, Janine; Bermudez, Yira; Alberts, David; Chow, H-H. Sherry] Univ Arizona Canc Ctr, Tucson, AZ USA.
[Tang, Jean; Rezaee, Melika; Lee, Alex] Stanford Univ, Stanford, CA 94305 USA.
[Hsu, Chiu-Hsieh] Univ Arizona, Tucson, AZ USA.
[Tangrea, Joe; Parnes, Howard] NCI, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD OCT 1
PY 2014
VL 74
IS 19
SU S
MA 3248
DI 10.1158/1538-7445.AM2014-3248
PG 1
WC Oncology
SC Oncology
GA CB8VR
UT WOS:000349910200249
ER
PT J
AU Czikora, A
Kedei, N
Blumberg, PM
AF Czikora, Agnes
Kedei, Noemi
Blumberg, Peter M.
TI Comparison of structural elements in RasGRP3 and RasGRP1 controlling
membrane interaction
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 105th Annual Meeting of the American-Association-for-Cancer-Research
(AACR)
CY APR 05-09, 2014
CL San Diego, CA
SP Amer Assoc Canc Res
C1 [Czikora, Agnes; Kedei, Noemi; Blumberg, Peter M.] NCI, Ctr Canc Res, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 2
U2 3
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD OCT 1
PY 2014
VL 74
IS 19
SU S
MA 4450
DI 10.1158/1538-7445.AM2014-4450
PG 1
WC Oncology
SC Oncology
GA CB8VR
UT WOS:000349910202423
ER
PT J
AU Decker, BJ
Karyadi, DM
Karlins, E
Davis, BW
Tillmans, LS
Thibodeau, SN
Ostrander, EA
AF Decker, Brennan J.
Karyadi, Danielle M.
Karlins, Eric
Davis, Brian W.
Tillmans, Lori S.
Thibodeau, Stephen N.
Ostrander, Elaine A.
TI Whole genome sequencing of high-grade treatment-naive prostate tumors
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 105th Annual Meeting of the American-Association-for-Cancer-Research
(AACR)
CY APR 05-09, 2014
CL San Diego, CA
SP Amer Assoc Canc Res
C1 [Decker, Brennan J.; Karyadi, Danielle M.; Karlins, Eric; Davis, Brian W.; Ostrander, Elaine A.] NIH, Bethesda, MD 20892 USA.
[Tillmans, Lori S.; Thibodeau, Stephen N.] Mayo Clin, Rochester, MN USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD OCT 1
PY 2014
VL 74
IS 19
SU S
MA 1536
DI 10.1158/1538-7445.AM2014-1536
PG 1
WC Oncology
SC Oncology
GA CB8UN
UT WOS:000349906901262
ER
PT J
AU Dexheimer, TS
Rosenthal, AS
Luci, D
Liang, Q
Villamil, MA
Jadhav, A
Simeonov, A
Zhuang, ZH
Maloney, DJ
AF Dexheimer, Thomas S.
Rosenthal, Andrew S.
Luci, Diane
Liang, Qin
Villamil, Mark A.
Jadhav, Ajit
Simeonov, Anton
Zhuang, Zhihao
Maloney, David J.
TI Discovery, synthesis, and structure-activity relationship of
N-benzyl-2-phenylpyrimidin-4-amine derivatives as potent USP1/UAF1
deubiquitinase inhibitors with anticancer activity against non-small
cell lung cancer
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 105th Annual Meeting of the American-Association-for-Cancer-Research
(AACR)
CY APR 05-09, 2014
CL San Diego, CA
SP Amer Assoc Canc Res
C1 [Dexheimer, Thomas S.; Rosenthal, Andrew S.; Luci, Diane; Jadhav, Ajit; Simeonov, Anton; Maloney, David J.] Natl Ctr Adv Translat Sci, Rockville, MD USA.
[Liang, Qin; Villamil, Mark A.; Zhuang, Zhihao] Univ Delaware, Newark, DE USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD OCT 1
PY 2014
VL 74
IS 19
SU S
MA LB-11
DI 10.1158/1538-7445.AM2014-LB-11
PG 1
WC Oncology
SC Oncology
GA CB8VR
UT WOS:000349910205145
ER
PT J
AU Dickherber, A
AF Dickherber, Anthony
TI Funding innovative technologies for cancer research at the National
Cancer Institute
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 105th Annual Meeting of the American-Association-for-Cancer-Research
(AACR)
CY APR 05-09, 2014
CL San Diego, CA
SP Amer Assoc Canc Res
C1 [Dickherber, Anthony] NCI, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD OCT 1
PY 2014
VL 74
IS 19
SU S
MA 3499
DI 10.1158/1538-7445.AM2014-3499
PG 1
WC Oncology
SC Oncology
GA CB8VR
UT WOS:000349910200496
ER
PT J
AU Dillenburg-Pilla, P
Patel, V
Mikelis, CM
Zarate-Blades, CR
Amornphimoltham, P
Wang, ZY
Martin, D
Leelahavanichkul, K
Doci, CL
Dorsam, RT
Masedunskas, A
Nohata, N
Weigert, R
Molinolo, AA
Gutkind, JS
AF Dillenburg-Pilla, Patricia
Patel, Vyomesh
Mikelis, Constantinos M.
Zarate-Blades, Carlos Rodrigo
Amornphimoltham, Panomwat
Wang, Zhiyong
Martin, Daniel
Leelahavanichkul, Kantima
Doci, Colleen L.
Dorsam, Robert T.
Masedunskas, Andrius
Nohata, Nijiro
Weigert, Roberto
Molinolo, Alfredo A.
Gutkind, J. Silvio
TI A central role for mTORC1 in CXCR4-mediated directional migration and
metastasis
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 105th Annual Meeting of the American-Association-for-Cancer-Research
(AACR)
CY APR 05-09, 2014
CL San Diego, CA
SP Amer Assoc Canc Res
C1 [Dillenburg-Pilla, Patricia; Patel, Vyomesh; Mikelis, Constantinos M.; Amornphimoltham, Panomwat; Wang, Zhiyong; Martin, Daniel; Leelahavanichkul, Kantima; Doci, Colleen L.; Dorsam, Robert T.; Masedunskas, Andrius; Nohata, Nijiro; Weigert, Roberto; Molinolo, Alfredo A.; Gutkind, J. Silvio] NIDCR, NIH, Bethesda, MD USA.
[Zarate-Blades, Carlos Rodrigo] NEI, NIH, Bethesda, MD 20892 USA.
RI Zarate-Blades, Carlos/C-9663-2015
OI Zarate-Blades, Carlos/0000-0002-7728-7869
NR 0
TC 0
Z9 0
U1 0
U2 1
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD OCT 1
PY 2014
VL 74
IS 19
SU S
MA 4050
DI 10.1158/1538-7445.AM2014-4050
PG 1
WC Oncology
SC Oncology
GA CB8VR
UT WOS:000349910202033
ER
PT J
AU Dine, J
Garimella, S
Gehlhaus, K
Grandin, M
Caplen, N
Lipkowitz, S
AF Dine, Jennifer
Garimella, Sireesha
Gehlhaus, Kristie
Grandin, Magda
Caplen, Natasha
Lipkowitz, Stanley
TI Identification and characterization of novel regulators of TRAIL-induced
apoptosis in breast cancer cells
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 105th Annual Meeting of the American-Association-for-Cancer-Research
(AACR)
CY APR 05-09, 2014
CL San Diego, CA
SP Amer Assoc Canc Res
C1 [Dine, Jennifer] NCI, NINR, Bethesda, MD 20892 USA.
[Garimella, Sireesha; Gehlhaus, Kristie; Grandin, Magda; Caplen, Natasha; Lipkowitz, Stanley] NCI, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD OCT 1
PY 2014
VL 74
IS 19
SU S
MA 5124
DI 10.1158/1538-7445.AM2014-5124
PG 1
WC Oncology
SC Oncology
GA CB8VR
UT WOS:000349910204077
ER
PT J
AU Ding, X
Sharan, SK
AF Ding, Xia
Sharan, Shyam K.
TI Identification of BRCA2 genetic interactors in an ES cell-based model
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 105th Annual Meeting of the American-Association-for-Cancer-Research
(AACR)
CY APR 05-09, 2014
CL San Diego, CA
SP Amer Assoc Canc Res
C1 [Ding, Xia; Sharan, Shyam K.] NCI, Frederick, MD 21701 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD OCT 1
PY 2014
VL 74
IS 19
SU S
MA 2390
DI 10.1158/1538-7445.AM2014-2390
PG 1
WC Oncology
SC Oncology
GA CB8UN
UT WOS:000349906903116
ER
PT J
AU Divakar, S
Caprio, RVD
Baker, SJ
Reddy, MVR
Ritt, DA
Morrison, DK
Reddy, EP
AF Divakar, SaiKrishna
Caprio, Rodrigo Vasqez-Del
Baker, Stacey J.
Reddy, M. V. Ramana
Ritt, Daniel A.
Morrison, Deborah K.
Reddy, E. Premkumar
TI Targeting the Ras-Binding domain of RAS effector proteins by a small
molecule inhibitor, Rigosertib
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 105th Annual Meeting of the American-Association-for-Cancer-Research
(AACR)
CY APR 05-09, 2014
CL San Diego, CA
SP Amer Assoc Canc Res
C1 [Divakar, SaiKrishna; Caprio, Rodrigo Vasqez-Del; Baker, Stacey J.; Reddy, M. V. Ramana; Reddy, E. Premkumar] Mt Sinai Sch Med, New York, NY USA.
[Ritt, Daniel A.; Morrison, Deborah K.] Natl Canc Inst, Frederick, MD USA.
NR 0
TC 0
Z9 0
U1 3
U2 5
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD OCT 1
PY 2014
VL 74
IS 19
SU S
MA LB-108
DI 10.1158/1538-7445.AM2014-LB-108
PG 1
WC Oncology
SC Oncology
GA CB8VR
UT WOS:000349910205143
ER
PT J
AU Dobi, A
Chen, YM
Ali, A
Young, D
Rosen, P
Farrell, J
Degon, M
Srivastava, S
Kagan, J
Lee, J
Cullen, J
Petrovics, G
McLeod, DG
Sesterhenn, IA
Srivastava, S
AF Dobi, Albert
Chen, Yongmei
Ali, Amina
Young, Denise
Rosen, Philip
Farrell, James
Degon, Michael
Srivastava, Sudhir
Kagan, Jacob
Lee, Jocelyn
Cullen, Jennifer
Petrovics, Gyorgy
McLeod, David G.
Sesterhenn, Isabell A.
Srivastava, Shiv
TI Potential impact on the biology and biomarker utility of ERG-typing in
the context of ethnic differences of prostate cancer
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 105th Annual Meeting of the American-Association-for-Cancer-Research
(AACR)
CY APR 05-09, 2014
CL San Diego, CA
SP Amer Assoc Canc Res
C1 [Dobi, Albert; Chen, Yongmei; Ali, Amina; Young, Denise; Cullen, Jennifer; Petrovics, Gyorgy; McLeod, David G.; Srivastava, Shiv] USUHS, CPDR, Dept Surg, Rockville, MD USA.
[Rosen, Philip; Farrell, James; Degon, Michael] Walter Reed Natl Mil Med Ctr, Bethesda, MD USA.
[Srivastava, Sudhir; Kagan, Jacob; Lee, Jocelyn] NCI, Canc Biomarkers Res Grp, Canc Prevent Div, Bethesda, MD 20892 USA.
[Sesterhenn, Isabell A.] Joint Pathol Ctr, Silver Spring, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD OCT 1
PY 2014
VL 74
IS 19
SU S
MA 1859
DI 10.1158/1538-7445.AM2014-1859
PG 2
WC Oncology
SC Oncology
GA CB8UN
UT WOS:000349906902076
ER
PT J
AU Dominianni, C
Sinha, R
Goedert, JJ
Pei, ZH
Yang, LY
Hayes, RB
Ahn, JY
AF Dominianni, Christine
Sinha, Rashmi
Goedert, James J.
Pei, Zhiheng
Yang, Liying
Hayes, Richard B.
Ahn, Jiyoung
TI Personal determinants of the human gut microbiome
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 105th Annual Meeting of the American-Association-for-Cancer-Research
(AACR)
CY APR 05-09, 2014
CL San Diego, CA
SP Amer Assoc Canc Res
C1 [Dominianni, Christine; Pei, Zhiheng; Yang, Liying; Hayes, Richard B.; Ahn, Jiyoung] NYU, Sch Med, New York, NY USA.
[Sinha, Rashmi; Goedert, James J.] NIH, Bethesda, MD 20892 USA.
RI Sinha, Rashmi/G-7446-2015;
OI Sinha, Rashmi/0000-0002-2466-7462; Yang, Liying/0000-0003-1442-4915;
Pei, Zhiheng/0000-0001-8570-6747; Hayes, Richard/0000-0002-0918-661X
NR 0
TC 0
Z9 0
U1 0
U2 2
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD OCT 1
PY 2014
VL 74
IS 19
SU S
MA 308
DI 10.1158/1538-7445.AM2014-308
PG 2
WC Oncology
SC Oncology
GA CB8UN
UT WOS:000349906904277
ER
PT J
AU Du, MM
Jiao, S
Rosse, SA
Gala, M
Abecasis, G
Bezieau, S
Brenner, H
Casey, G
Chang-Claude, J
Gallinger, S
Hudson, TJ
Kury, S
Marchand, LL
Leal, SM
Newcomb, PA
Nickerson, DA
Potter, JD
Slattery, ML
Hsu, L
Chan, AT
White, E
Berndt, SI
Peters, U
AF Du, Mengmeng
Jiao, Shuo
Rosse, Stephanie A.
Gala, Manish
Abecasis, Goncalo
Bezieau, Stephane
Brenner, Hermann
Casey, Graham
Chang-Claude, Jenny
Gallinger, Steven
Hudson, Thomas J.
Kuery, Sebastien
Marchand, Loic L.
Leal, Suzanne M.
Newcomb, Polly A.
Nickerson, Deborah A.
Potter, John D.
Slattery, Martha L.
Hsu, Li
Chan, Andrew T.
White, Emily
Berndt, Sonja I.
Peters, Ulrike
TI Fine-mapping of common genetic variants associated with colorectal tumor
risk identified potential functional variants
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 105th Annual Meeting of the American-Association-for-Cancer-Research
(AACR)
CY APR 05-09, 2014
CL San Diego, CA
SP Amer Assoc Canc Res
C1 [Du, Mengmeng; Jiao, Shuo; Rosse, Stephanie A.; Newcomb, Polly A.; Potter, John D.; Hsu, Li; White, Emily; Peters, Ulrike] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
[Gala, Manish; Chan, Andrew T.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Abecasis, Goncalo] Univ Michigan, Sch Publ Hlth, Ann Arbor, MI 48109 USA.
[Bezieau, Stephane; Kuery, Sebastien] CHU Nantes, F-44035 Nantes 01, France.
[Brenner, Hermann; Chang-Claude, Jenny] German Canc Res Ctr, Heidelberg, Germany.
[Casey, Graham] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA.
[Gallinger, Steven] Mt Sinai Hosp, Toronto, PE, Canada.
[Hudson, Thomas J.] Univ Toronto, Toronto, ON, Canada.
[Marchand, Loic L.] Univ Hawaii, Ctr Canc, Honolulu, HI 96822 USA.
[Leal, Suzanne M.] Baylor Coll Med, Houston, TX 77030 USA.
[Nickerson, Deborah A.] Univ Washington, Seattle, WA 98195 USA.
[Slattery, Martha L.] Univ Utah, Hlth Sci Ctr, Salt Lake City, UT USA.
[Berndt, Sonja I.] NCI, NIH, Bethesda, MD 20892 USA.
RI KURY, Sebastien/G-5971-2015; Bezieau, stephane/G-5621-2015
OI KURY, Sebastien/0000-0001-5497-0465; Bezieau,
stephane/0000-0003-0095-1319
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD OCT 1
PY 2014
VL 74
IS 19
SU S
MA 2190
DI 10.1158/1538-7445.AM2014-2190
PG 2
WC Oncology
SC Oncology
GA CB8UN
UT WOS:000349906902401
ER
PT J
AU Edelman, DC
Petersen, D
Gomez, A
Gadalla, S
Webster, P
Dennis, L
Krouse, M
Savage, S
Meltzer, PS
AF Edelman, Daniel C.
Petersen, David
Gomez, Allison
Gadalla, Shahinaz
Webster, Philippa
Dennis, Lucas
Krouse, Mike
Savage, Sharon
Meltzer, Paul S.
TI Development of a direct-measurement molecular assay to determine
telomere length in human samples
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 105th Annual Meeting of the American-Association-for-Cancer-Research
(AACR)
CY APR 05-09, 2014
CL San Diego, CA
SP Amer Assoc Canc Res
C1 [Edelman, Daniel C.; Petersen, David; Gomez, Allison; Gadalla, Shahinaz; Savage, Sharon; Meltzer, Paul S.] NCI, NIH, Bethesda, MD 20892 USA.
[Webster, Philippa; Dennis, Lucas; Krouse, Mike] NanoString Inc, Seattle, WA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD OCT 1
PY 2014
VL 74
IS 19
SU S
MA 5100
DI 10.1158/1538-7445.AM2014-5100
PG 1
WC Oncology
SC Oncology
GA CB8VR
UT WOS:000349910204054
ER
PT J
AU Eiseman, JL
Holleran, J
McCormick, DL
Muzzio, M
Covey, JM
Khanna, C
Mazcko, C
Pommier, Y
Paoloni, M
Doroshow, JD
Tomaszewski, JE
Beumer, JH
AF Eiseman, Julie L.
Holleran, Julianne
McCormick, David L.
Muzzio, Miguel
Covey, Joseph M.
Khanna, Chand
Mazcko, Christina
Pommier, Yves
Paoloni, Melissa
Doroshow, James D.
Tomaszewski, Joseph E.
Beumer, Jan H.
TI Plasma and tumor pharmacokinetics of IV LMP400, a novel
indenoisoquinoline topoisomerase I inhibitor, in a canine phase I study
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 105th Annual Meeting of the American-Association-for-Cancer-Research
(AACR)
CY APR 05-09, 2014
CL San Diego, CA
SP Amer Assoc Canc Res
C1 [Eiseman, Julie L.; Holleran, Julianne; Beumer, Jan H.] Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA.
[McCormick, David L.; Muzzio, Miguel] ITT Res Inst, Chicago, IL USA.
[Covey, Joseph M.; Khanna, Chand; Mazcko, Christina; Pommier, Yves; Paoloni, Melissa; Doroshow, James D.; Tomaszewski, Joseph E.] NCI, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD OCT 1
PY 2014
VL 74
IS 19
SU S
MA 4632
DI 10.1158/1538-7445.AM2014-4632
PG 2
WC Oncology
SC Oncology
GA CB8VR
UT WOS:000349910203106
ER
PT J
AU Ekenga, CC
AF Ekenga, Christine C.
TI A prospective study of breast cancer risk associated with occupational
exposure to potentially endocrine disrupting compounds
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 105th Annual Meeting of the American-Association-for-Cancer-Research
(AACR)
CY APR 05-09, 2014
CL San Diego, CA
SP Amer Assoc Canc Res
C1 [Ekenga, Christine C.] NIEHS, Res Triangle Pk, NC 27709 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD OCT 1
PY 2014
VL 74
IS 19
SU S
MA LB-283
DI 10.1158/1538-7445.AM2014-LB-283
PG 1
WC Oncology
SC Oncology
GA CB8VR
UT WOS:000349910205315
ER
PT J
AU El Touny, LH
Vieira, A
Mendoza, A
Khanna, C
Hoenerhoff, MJ
Green, JE
AF El Touny, Lara H.
Vieira, Anthony
Mendoza, Arnulfo
Khanna, Chand
Hoenerhoff, Mark J.
Green, Jeffrey E.
TI Identification of a novel combination therapy that prevents the
metastatic outgrowth and reduces the viability of dormant breast cancer
cells
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 105th Annual Meeting of the American-Association-for-Cancer-Research
(AACR)
CY APR 05-09, 2014
CL San Diego, CA
SP Amer Assoc Canc Res
C1 [El Touny, Lara H.; Vieira, Anthony; Mendoza, Arnulfo; Khanna, Chand; Green, Jeffrey E.] NCI, Bethesda, MD 20892 USA.
[Hoenerhoff, Mark J.] NIEHS, Res Triangle Pk, NC 27709 USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD OCT 1
PY 2014
VL 74
IS 19
SU S
MA 4028
DI 10.1158/1538-7445.AM2014-4028
PG 1
WC Oncology
SC Oncology
GA CB8VR
UT WOS:000349910202012
ER
PT J
AU Emons, G
Spitzner, M
Reineke, S
Moller, J
Kendziorra, E
Beissbarth, T
Rave-Fraenk, M
Gaedcke, J
Ried, T
Ghadimi, M
Grade, M
AF Emons, Georg
Spitzner, Melanie
Reineke, Sebastian
Moeller, Janneke
Kendziorra, Emil
Beissbarth, Tim
Rave-Fraenk, Margret
Gaedcke, Jochen
Ried, Thomas
Ghadimi, Michael
Grade, Marian
TI Wnt/beta-catenin signaling mediates resistance of colorectal cancer
cells to chemoradiotherapy
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 105th Annual Meeting of the American-Association-for-Cancer-Research
(AACR)
CY APR 05-09, 2014
CL San Diego, CA
SP Amer Assoc Canc Res
C1 [Emons, Georg; Spitzner, Melanie; Reineke, Sebastian; Moeller, Janneke; Kendziorra, Emil; Gaedcke, Jochen; Ghadimi, Michael; Grade, Marian] Univ Med Ctr, Dept Gen Visceral & Pediat Surg, Gottingen, Germany.
[Beissbarth, Tim] Dept Med Genet, Gottingen, Germany.
[Rave-Fraenk, Margret] Univ Med Ctr, Dept Radiotherapy & Radiooncol, Gottingen, Germany.
[Ried, Thomas] NCI, Genet Branch, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD OCT 1
PY 2014
VL 74
IS 19
SU S
MA 3946
DI 10.1158/1538-7445.AM2014-3946
PG 1
WC Oncology
SC Oncology
GA CB8VR
UT WOS:000349910201430
ER
PT J
AU Evans, DM
Delosh, R
Laudeman, J
Ogle, C
Reinhart, R
Selby, M
Silvers, T
Connelly, J
Monks, A
Polley, E
Kaur, G
Morris, J
Teicher, B
AF Evans, David M.
Delosh, Rene
Laudeman, Julie
Ogle, Chad
Reinhart, Russell
Selby, Michael
Silvers, Thomas
Connelly, John
Monks, Anne
Polley, Eric
Kaur, Gurmeet
Morris, Joel
Teicher, Beverly
TI Screening more than 60 human SCLC lines with approved and
investigational agents indicates complex patterns of response:
Identification of HSP90 and HDACs as potential targets
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 105th Annual Meeting of the American-Association-for-Cancer-Research
(AACR)
CY APR 05-09, 2014
CL San Diego, CA
SP Amer Assoc Canc Res
C1 [Evans, David M.; Delosh, Rene; Laudeman, Julie; Ogle, Chad; Reinhart, Russell; Selby, Michael; Silvers, Thomas; Connelly, John; Monks, Anne] FNCRL, Frederick, MD USA.
[Polley, Eric; Kaur, Gurmeet; Morris, Joel; Teicher, Beverly] NCI, Div Canc Treatment & Diag, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD OCT 1
PY 2014
VL 74
IS 19
SU S
MA 5450
DI 10.1158/1538-7445.AM2014-5450
PG 1
WC Oncology
SC Oncology
GA CB8VR
UT WOS:000349910204368
ER
PT J
AU Eytan, DF
Snow, GE
Chen, Z
Van Waes, C
AF Eytan, Danielle F.
Snow, Grace E.
Chen, Zhong
Van Waes, Carter
TI Novel SMAC-mimetic birinapant demonstrates preclinical antitumor
activity in human xenograft head and neck cancer models exhibiting
alterations in cell death pathway components FADD, BIRC2, or CASP8
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 105th Annual Meeting of the American-Association-for-Cancer-Research
(AACR)
CY APR 05-09, 2014
CL San Diego, CA
SP Amer Assoc Canc Res
C1 [Eytan, Danielle F.; Snow, Grace E.; Chen, Zhong; Van Waes, Carter] Natl Inst Deafness & Other Commun Disorders, Head & Neck Surg Branch, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD OCT 1
PY 2014
VL 74
IS 19
SU S
MA 2771
DI 10.1158/1538-7445.AM2014-2771
PG 2
WC Oncology
SC Oncology
GA CB8UN
UT WOS:000349906904028
ER
PT J
AU Falk, RT
Dallal, CM
Lacey, JV
Bauer, DC
Buist, DS
Cauley, JA
Hue, TF
LaCroix, A
Tice, JA
Pfeiffer, RM
Xu, X
Veenstra, TD
Brinton, LA
AF Falk, Roni T.
Dallal, Cher M.
Lacey, James V.
Bauer, Douglas C.
Buist, Diana S.
Cauley, Jane A.
Hue, Trisha F.
LaCroix, Andrea
Tice, Jeffrey A.
Pfeiffer, Ruth M.
Xu, Xia
Veenstra, Timothy D.
Brinton, Louise A.
TI Estrogen metabolites and colorectal cancer risk in postmenopausal women
in the Breast and Bone Follow-up to the Fracture Intervention Trial (B
similar to FIT)
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 105th Annual Meeting of the American-Association-for-Cancer-Research
(AACR)
CY APR 05-09, 2014
CL San Diego, CA
SP Amer Assoc Canc Res
C1 [Falk, Roni T.; Pfeiffer, Ruth M.; Brinton, Louise A.] NCI, Bethesda, MD 20892 USA.
[Dallal, Cher M.] Univ Maryland, Sch Publ Hlth, College Pk, MD 20742 USA.
[Lacey, James V.] City Hope Natl Med Ctr, Beckman Res Inst, Duarte, CA USA.
[Bauer, Douglas C.; Hue, Trisha F.; Tice, Jeffrey A.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Buist, Diana S.] Grp Hlth Res Inst, Seattle, WA USA.
[Cauley, Jane A.] Univ Pittsburgh, Pittsburgh, PA USA.
[LaCroix, Andrea] Univ Washington, Seattle, WA 98195 USA.
[Xu, Xia; Veenstra, Timothy D.] NCI, Frederick Natl Lab Canc Res, Frederick, MD 21701 USA.
RI Brinton, Louise/G-7486-2015
OI Brinton, Louise/0000-0003-3853-8562
NR 0
TC 0
Z9 0
U1 0
U2 1
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD OCT 1
PY 2014
VL 74
IS 19
SU S
MA 1603
DI 10.1158/1538-7445.AM2014-1603
PG 2
WC Oncology
SC Oncology
GA CB8UN
UT WOS:000349906901327
ER
PT J
AU Fallon, JK
Tighe, R
Lyon, AJ
Sabzevari, H
Schlom, J
Greiner, JW
AF Fallon, Jonathan K.
Tighe, Robert
Lyon, Amanda J.
Sabzevari, Helen
Schlom, Jeffrey
Greiner, John W.
TI The immunocytokine NHS-IL12 as a potential cancer therapeutic
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 105th Annual Meeting of the American-Association-for-Cancer-Research
(AACR)
CY APR 05-09, 2014
CL San Diego, CA
SP Amer Assoc Canc Res
C1 [Fallon, Jonathan K.; Lyon, Amanda J.; Schlom, Jeffrey; Greiner, John W.] NCI, Bethesda, MD 20892 USA.
[Tighe, Robert; Sabzevari, Helen] EMD Serono, Billerica, MA USA.
NR 0
TC 0
Z9 0
U1 2
U2 2
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD OCT 1
PY 2014
VL 74
IS 19
SU S
MA 2573
DI 10.1158/1538-7445.AM2014-2573
PG 1
WC Oncology
SC Oncology
GA CB8UN
UT WOS:000349906903314
ER
PT J
AU Faucz, FR
Beuschlei, F
Fassnacht, M
Assie, G
Calebiro, D
Stratakis, C
Osswald, A
Ronchi, CL
Wieland, T
Sbiera, S
Schaak, K
Schmittfull, A
Schwarzmayr, T
Barreau, O
Vezzosi, D
Rizk-Rabbin, M
Zabel, U
Szarek, E
Salpea, P
Forlino, A
Vetro, A
Zuffardi, O
Kisker, C
Diener, S
Meitinger, T
Lohse, MJ
Reincke, M
Bertherat, J
Strom, TM
Allolio, B
AF Faucz, Fabio R.
Beuschlei, Felix
Fassnacht, Martin
Assie, Guilaume
Calebiro, Davide
Stratakis, Constantine
Osswald, Andrea
Ronchi, Cristina L.
Wieland, Thomas
Sbiera, Silviu
Schaak, Katrin
Schmittfull, Anett
Schwarzmayr, Thomas
Barreau, Olivia
Vezzosi, Delphine
Rizk-Rabbin, Marthe
Zabel, Ulrike
Szarek, Eva
Salpea, Paraskevi
Forlino, Antonella
Vetro, Annalisa
Zuffardi, Orsetta
Kisker, Caroline
Diener, Susanne
Meitinger, Thomas
Lohse, Martin J.
Reincke, Martin
Bertherat, Jerome
Strom, Tim M.
Allolio, Bruno
TI Constitutive activation of PRKACA in adrenal Cushing's syndrome
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 105th Annual Meeting of the American-Association-for-Cancer-Research
(AACR)
CY APR 05-09, 2014
CL San Diego, CA
SP Amer Assoc Canc Res
C1 [Faucz, Fabio R.; Stratakis, Constantine; Szarek, Eva; Salpea, Paraskevi] NICHD, NIH, PDEGEN, Bethesda, MD USA.
[Beuschlei, Felix; Fassnacht, Martin; Osswald, Andrea; Sbiera, Silviu; Schaak, Katrin; Reincke, Martin] Univ Munich, Med Klin & Poliklin 4, Munich, Germany.
[Assie, Guilaume; Barreau, Olivia; Vezzosi, Delphine; Rizk-Rabbin, Marthe; Bertherat, Jerome] Univ Paris 05, INSERM U1016, CNRS UMR 8104, Inst Cochin,Fac Med Paris Descartes, Paris, France.
[Calebiro, Davide; Zabel, Ulrike; Kisker, Caroline; Lohse, Martin J.] Univ Wurzburg, Rudolf Virchow Ctr Expt Biomed, D-97070 Wurzburg, Germany.
[Ronchi, Cristina L.; Schmittfull, Anett] Univ Wurzburg, Comprehens Canc Ctr Mainfranken, D-97070 Wurzburg, Germany.
[Wieland, Thomas; Schwarzmayr, Thomas; Diener, Susanne; Meitinger, Thomas; Strom, Tim M.] Helmholtz Zentrum Munchen, Inst Human Genet, Neuherberg, Germany.
[Forlino, Antonella; Vetro, Annalisa; Zuffardi, Orsetta] Univ Pavia, Dipartimento Med Mol, Genet Med, I-27100 Pavia, Italy.
[Allolio, Bruno] Univ Wurzburg, Univ Hosp, Dept Med 1, Endocrine & Diabet Unit, D-97070 Wurzburg, Germany.
RI Forlino, Antonella/H-5385-2015
OI Forlino, Antonella/0000-0002-6385-1182
NR 0
TC 0
Z9 0
U1 0
U2 1
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD OCT 1
PY 2014
VL 74
IS 19
SU S
MA LB-182
DI 10.1158/1538-7445.AM2014-LB-182
PG 2
WC Oncology
SC Oncology
GA CB8VR
UT WOS:000349910205216
ER
PT J
AU Faucz, FR
Zilbermint, M
Assie, G
Lodish, MB
Szarek, E
Trivellin, G
Berthon, A
Sinaii, N
Libe, R
Espiard, S
Drougat, L
Ragazzon, B
Feldman, B
Bertherat, J
Stratakis, CA
AF Faucz, Fabio R.
Zilbermint, Mihail
Assie, Guillaume
Lodish, Maya B.
Szarek, Eva
Trivellin, Giampaolo
Berthon, Annabel
Sinaii, Ninet
Libe, Rossella
Espiard, Stephanie
Drougat, Ludivine
Ragazzon, Bruno
Feldman, Benjamin
Bertherat, Jerome
Stratakis, Constantine A.
TI Macronodular adrenal hyperplasia due to mutations in ARMC5: New
mutations in humans and modeling in zebrafish
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 105th Annual Meeting of the American-Association-for-Cancer-Research
(AACR)
CY APR 05-09, 2014
CL San Diego, CA
SP Amer Assoc Canc Res
C1 [Faucz, Fabio R.; Zilbermint, Mihail; Lodish, Maya B.; Szarek, Eva; Trivellin, Giampaolo; Stratakis, Constantine A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Endocrinol & Genet, NIH, Bethesda, MD USA.
[Assie, Guillaume; Berthon, Annabel; Libe, Rossella; Espiard, Stephanie; Drougat, Ludivine; Ragazzon, Bruno; Bertherat, Jerome] CNRS, INSERM, Dept Endocrinol Metab & Canc, Inst Cochin, Paris, France.
[Sinaii, Ninet] NIH, Biostat & Clin Epidemiol Serv, Ctr Clin, Bethesda, MD 20892 USA.
[Feldman, Benjamin] NICHD, NICHD Zebrafish Core, Program Genom Differentiat, NIH, Bethesda, MD USA.
NR 0
TC 1
Z9 1
U1 1
U2 1
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD OCT 1
PY 2014
VL 74
IS 19
SU S
MA 2239
DI 10.1158/1538-7445.AM2014-2239
PG 2
WC Oncology
SC Oncology
GA CB8UN
UT WOS:000349906902450
ER
PT J
AU Fehringer, G
Brenner, D
Zhang, ZF
Lee, YCA
Matsuo, K
Stucker, I
Vineis, P
Boffetta, P
Brennan, P
Landi, MT
Morgenstern, H
Harris, CC
Lan, Q
Hong, YC
Siemiatycki, J
McLaughlin, JR
Lazarus, P
Muscat, J
Schwartz, AG
Dios, JMB
Ravina, AR
Rennert, G
Christiani, DC
Tardon, A
Marchand, LL
Orlow, I
Duell, EJ
Andrew, AS
Brenner, H
Consonni, D
Olsson, A
Straif, K
Hung, RJ
AF Fehringer, Gordon
Brenner, Darren
Zhang, Zuo-Feng
Lee, Yuan-Chin Amy
Matsuo, Keitaro
Stucker, Isabelle
Vineis, Paolo
Boffetta, Paolo
Brennan, Paul
Landi, Maria T.
Morgenstern, Hal
Harris, Curtis C.
Lan, Qing
Hong, Yun-Chul
Siemiatycki, Jack
McLaughlin, John R.
Lazarus, Philip
Muscat, Joshua
Schwartz, Ann G.
Barros Dios, Juan M.
Ravina, Alberto R.
Rennert, Gad
Christiani, David C.
Tardon, Adonina
Marchand, Loic L.
Orlow, Irene
Duell, Eric J.
Andrew, Angeline S.
Brenner, Hermann
Consonni, Dario
Olsson, Ann
Straif, Kurt
Hung, Rayjean J.
TI Alcohol and lung cancer risk: a pooled analysis using International Lung
Cancer Consortium studies
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 105th Annual Meeting of the American-Association-for-Cancer-Research
(AACR)
CY APR 05-09, 2014
CL San Diego, CA
SP Amer Assoc Canc Res
C1 [Fehringer, Gordon; Hung, Rayjean J.] Lunenfeld Tanenbaum Res Inst, Toronto, ON, Canada.
[Brenner, Darren; Brennan, Paul; Olsson, Ann; Straif, Kurt] IARC, Lyon, France.
[Zhang, Zuo-Feng] Univ Calif Los Angeles, Los Angeles, CA USA.
[Lee, Yuan-Chin Amy] Univ Utah, Salt Lake City, UT USA.
[Matsuo, Keitaro] Kyushu Univ, Fac Med Sci, Kyushu, Japan.
[Stucker, Isabelle] INSERM, U170, Villejuif, France.
[Vineis, Paolo] Univ London Imperial Coll Sci Technol & Med, London, England.
[Boffetta, Paolo] Mt Sinai Sch Med, New York, NY USA.
[Landi, Maria T.; Harris, Curtis C.; Lan, Qing] NCI, Bethesda, MD 20892 USA.
[Morgenstern, Hal] Univ Michigan, Ann Arbor, MI 48109 USA.
[Hong, Yun-Chul] Seoul Natl Univ, Coll Med, Seoul, South Korea.
[Siemiatycki, Jack] Univ Montreal Hosp Res Ctr CRCHUM, Montreal, PQ, Canada.
[Siemiatycki, Jack] Sch Publ Hlth, Montreal, PQ, Canada.
[McLaughlin, John R.] Publ Hlth Ontario, Toronto, ON, Canada.
[Lazarus, Philip; Muscat, Joshua] Penn State Univ, Coll Med, Hershey, PA USA.
[Schwartz, Ann G.] Wayne State Univ, Detroit, MI USA.
[Barros Dios, Juan M.; Ravina, Alberto R.] Univ Santiago de Compostela, Santiago De Compostela, Spain.
[Rennert, Gad] Technion Israel Inst Technol, Haifa, Israel.
[Rennert, Gad] Natl Canc Control Ctr, Clalit Hlth Serv, Haifa, Israel.
[Christiani, David C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA.
[Tardon, Adonina] Univ Oviedo, Univ Inst Oncol, Oviedo, Spain.
[Marchand, Loic L.] Univ Hawaii, Ctr Canc, Honolulu, HI 96822 USA.
[Orlow, Irene] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
[Duell, Eric J.] Catalan Inst Oncol ICO, Barcelona, Spain.
[Andrew, Angeline S.] Geisel Sch Med Dartmouth, Lebanon, PA USA.
[Brenner, Hermann] German Canc Res Ctr, Heidelberg, Germany.
[Consonni, Dario] Fdn IRCCS Ca Granda Osped Maggiore Policlin, Milan, Italy.
RI Consonni, Dario/K-7943-2016
OI Consonni, Dario/0000-0002-8935-3843
NR 0
TC 0
Z9 0
U1 0
U2 1
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD OCT 1
PY 2014
VL 74
IS 19
SU S
MA 1274
DI 10.1158/1538-7445.AM2014-1274
PG 2
WC Oncology
SC Oncology
GA CB8UN
UT WOS:000349906901013
ER
PT J
AU Felsenstein, KM
Simmons, JK
Gareiss, P
Mock, BA
Schneekloth, JS
AF Felsenstein, Kenneth M.
Simmons, John K.
Gareiss, Peter
Mock, Beverly A.
Schneekloth, John 'Jay' S.
TI Identification and biological characterization of a novel class of small
molecules to inhibit c-myc transcription
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 105th Annual Meeting of the American-Association-for-Cancer-Research
(AACR)
CY APR 05-09, 2014
CL San Diego, CA
SP Amer Assoc Canc Res
C1 [Felsenstein, Kenneth M.; Simmons, John K.; Mock, Beverly A.; Schneekloth, John 'Jay' S.] NCI, Bethesda, MD 20892 USA.
[Gareiss, Peter] Yale Univ, West Haven, CT USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD OCT 1
PY 2014
VL 74
IS 19
SU S
MA 1629
DI 10.1158/1538-7445.AM2014-1629
PG 1
WC Oncology
SC Oncology
GA CB8UN
UT WOS:000349906901351
ER
PT J
AU Feng, Y
Chen, GK
Stram, DO
Millikan, RC
Ambrosone, CB
John, EM
Bernstein, L
Zheng, W
Olshan, AF
Hu, JJ
Ziegler, RG
Nyante, S
Bandera, EV
Ingles, SA
Press, MF
Deming, SL
Rodriguez-Gil, JL
Palmer, JR
Olopade, OI
Huo, DZ
Adebamowo, CA
Ogundiran, T
Stram, A
Park, K
Rand, KA
Chanock, SJ
Marchand, LL
Kolonel, LN
Conti, DV
Easton, D
Henderson, BE
Haiman, CA
AF Feng, Ye
Chen, Gary K.
Stram, Daniel O.
Millikan, Robert C.
Ambrosone, Christine B.
John, Esther M.
Bernstein, Leslie
Zheng, Wei
Olshan, Andrew F.
Hu, Jennifer J.
Ziegler, Regina G.
Nyante, Sarah
Bandera, Elisa V.
Ingles, Sue A.
Press, Michael F.
Deming, Sandra L.
Rodriguez-Gil, Jorge L.
Palmer, Julie R.
Olopade, Olufunmilayo I.
Huo, Dezheng
Adebamowo, Clement A.
Ogundiran, Temidayo
Stram, Alex
Park, Karen
Rand, Kristin A.
Chanock, Stephen J.
Marchand, Loic L.
Kolonel, Laurence N.
Conti, David V.
Easton, Douglas
Henderson, Brian E.
Haiman, Christopher A.
TI A comprehensive examination of breast cancer risk loci in African
American women
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 105th Annual Meeting of the American-Association-for-Cancer-Research
(AACR)
CY APR 05-09, 2014
CL San Diego, CA
SP Amer Assoc Canc Res
C1 [Feng, Ye; Chen, Gary K.; Stram, Daniel O.; Ingles, Sue A.; Press, Michael F.; Stram, Alex; Park, Karen; Rand, Kristin A.; Conti, David V.; Henderson, Brian E.; Haiman, Christopher A.] Univ So Calif, Los Angeles, CA USA.
[Millikan, Robert C.; Olshan, Andrew F.] Univ N Carolina, Chapel Hill, NC USA.
[Ambrosone, Christine B.] Roswell Pk Canc Inst, Buffalo, NY 14263 USA.
[John, Esther M.] Canc Prevent Inst Calif, Fremont, CA USA.
[Bernstein, Leslie] City Hope Natl Med Ctr, Beckman Res Inst, Duarte, CA USA.
[Zheng, Wei; Deming, Sandra L.] Vanderbilt Univ, Sch Med, Nashville, TN 37212 USA.
[Hu, Jennifer J.; Rodriguez-Gil, Jorge L.] Univ Miami, Miller Sch Med, Miami, FL 33136 USA.
[Ziegler, Regina G.; Nyante, Sarah; Chanock, Stephen J.] NCI, Bethesda, MD 20892 USA.
[Bandera, Elisa V.] Rutgers Canc Inst New Jersey, New Brunswick, NJ USA.
[Palmer, Julie R.] Boston Univ, Slone Epidemiol Ctr, Boston, MA 02215 USA.
[Olopade, Olufunmilayo I.; Huo, Dezheng] Univ Chicago, Chicago, IL 60637 USA.
[Adebamowo, Clement A.] Univ Maryland, Baltimore, MD 21201 USA.
[Ogundiran, Temidayo] Univ Ibadan, Ibadan, Nigeria.
[Marchand, Loic L.; Kolonel, Laurence N.] Univ Hawaii, Ctr Canc, Honolulu, HI 96822 USA.
[Easton, Douglas] Univ Cambridge, Cambridge, England.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD OCT 1
PY 2014
VL 74
IS 19
SU S
MA 943
DI 10.1158/1538-7445.AM2014-943
PG 2
WC Oncology
SC Oncology
GA CB8UN
UT WOS:000349906905407
ER
PT J
AU Fer, ND
Harris, E
Fox, S
Zhou, M
Simpson, C
Liu, J
Korboukh, I
Hull-Ryde, EA
Janzen, WP
Frye, SV
Monks, A
Teicher, B
Rapisarda, A
AF Fer, Nicole D.
Harris, Erik
Fox, Stephen
Zhou, Ming
Simpson, Catherine
Liu, Jing
Korboukh, Ilia
Hull-Ryde, Emily A.
Janzen, William P.
Frye, Stephen V.
Monks, Anne
Teicher, Beverly
Rapisarda, Annamaria
TI Development and characterization of a cell based assay for the
validation of mutant IDH1 inhibitors
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 105th Annual Meeting of the American-Association-for-Cancer-Research
(AACR)
CY APR 05-09, 2014
CL San Diego, CA
SP Amer Assoc Canc Res
C1 [Fer, Nicole D.; Harris, Erik; Fox, Stephen; Zhou, Ming; Monks, Anne; Rapisarda, Annamaria] Leidos Biomed Res Inc, Frederick, MD USA.
[Simpson, Catherine; Liu, Jing; Korboukh, Ilia; Hull-Ryde, Emily A.; Janzen, William P.; Frye, Stephen V.] Univ N Carolina, Eshelman Sch Pharm, Div Chem Biol & Med Chem, Ctr Integrat Chem Biol & Drug Discovery, Chapel Hill, NC USA.
[Teicher, Beverly] NCI, Mol Pharmacol Lab, Div Canc Treatment & Diag, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 1
U2 3
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD OCT 1
PY 2014
VL 74
IS 19
SU S
MA 3741
DI 10.1158/1538-7445.AM2014-3741
PG 1
WC Oncology
SC Oncology
GA CB8VR
UT WOS:000349910201231
ER
PT J
AU Fernandez, E
Mistry, H
Brightman, F
Orrell, D
Dahut, WL
Figg, WD
Stein, WD
Chassagnole, C
AF Fernandez, Eric
Mistry, Hitesh
Brightman, Frances
Orrell, David
Dahut, William L.
Figg, William D.
Stein, Wilfried D.
Chassagnole, Christophe
TI Translational modeling of docetaxel-thalidomide combination treatment in
metastatic, castrate-resistant prostate cancer: predicting clinical
response using preclinical data
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 105th Annual Meeting of the American-Association-for-Cancer-Research
(AACR)
CY APR 05-09, 2014
CL San Diego, CA
SP Amer Assoc Canc Res
C1 [Fernandez, Eric; Mistry, Hitesh; Brightman, Frances; Orrell, David; Chassagnole, Christophe] Physiomics Plc, Oxford, England.
[Dahut, William L.; Figg, William D.; Stein, Wilfried D.] NCI, NIH, Bethesda, MD 20892 USA.
RI Figg Sr, William/M-2411-2016
NR 0
TC 0
Z9 0
U1 1
U2 2
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD OCT 1
PY 2014
VL 74
IS 19
SU S
MA 366
DI 10.1158/1538-7445.AM2014-366
PG 2
WC Oncology
SC Oncology
GA CB8UN
UT WOS:000349906904333
ER
PT J
AU Fiebig, HH
Maier, A
Kelter, G
Vuaroqueaux, V
Hariprakasha, HK
Michejda, C
AF Fiebig, Heinz H.
Maier, Armin
Kelter, Gerhard
Vuaroqueaux, Vincent
Hariprakasha, Humcha K.
Michejda, Christopher
TI In vitro anticancer activity of imidazo-acridinone (HKH40A) in panels of
human patient-derived tumor xenografts (PDXs) and human leukemia and
lymphoma cell lines
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 105th Annual Meeting of the American-Association-for-Cancer-Research
(AACR)
CY APR 05-09, 2014
CL San Diego, CA
SP Amer Assoc Canc Res
C1 [Fiebig, Heinz H.; Maier, Armin; Kelter, Gerhard; Vuaroqueaux, Vincent] Oncotest GmbH, Freiburg, Germany.
[Hariprakasha, Humcha K.; Michejda, Christopher] NCI, Lab Mol Aspects Drug Design, Ctr Canc Res, Frederick, MD 21701 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD OCT 1
PY 2014
VL 74
IS 19
SU S
MA 1231
DI 10.1158/1538-7445.AM2014-1231
PG 1
WC Oncology
SC Oncology
GA CB8UN
UT WOS:000349906900469
ER
PT J
AU Fu, YP
Kohaar, I
Moore, L
Lenz, P
Figueroa, JD
Tang, W
Porter-Gill, P
Chanock, S
Hewitt, SM
Silverman, DT
Rothman, N
Prokunina-Olsson, L
AF Fu, Yi-Ping
Kohaar, Indu
Moore, Lee
Lenz, Petra
Figueroa, Jonine D.
Tang, Wei
Porter-Gill, Patricia
Chanock, Stephen
Hewitt, Stephen M.
Silverman, Debra T.
Rothman, Nathaniel
Prokunina-Olsson, Ludmila
CA NCI-GWAS Bladder Canc Consortium
TI Translational implications of the 19q12 bladder cancer GWAS signal for
aggressive bladder cancer
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 105th Annual Meeting of the American-Association-for-Cancer-Research
(AACR)
CY APR 05-09, 2014
CL San Diego, CA
SP Amer Assoc Canc Res
C1 [Fu, Yi-Ping; Kohaar, Indu; Moore, Lee; Lenz, Petra; Figueroa, Jonine D.; Tang, Wei; Porter-Gill, Patricia; Chanock, Stephen; Hewitt, Stephen M.; Silverman, Debra T.; Rothman, Nathaniel; Prokunina-Olsson, Ludmila; NCI-GWAS Bladder Canc Consortium] NCI, DCEG, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD OCT 1
PY 2014
VL 74
IS 19
SU S
MA 944
DI 10.1158/1538-7445.AM2014-944
PG 1
WC Oncology
SC Oncology
GA CB8UN
UT WOS:000349906905408
ER
PT J
AU Gamache, BJ
Simmons, JK
Michalowski, A
Patel, J
Zhang, K
Zhang, SL
DuBois, W
Zingone, A
Kuehl, M
Huang, J
Landgren, O
Mock, B
AF Gamache, Benjamin J.
Simmons, John K.
Michalowski, Aleksandra
Patel, Jyoti
Zhang, Ke
Zhang, Shuling
DuBois, Wendy
Zingone, Adriana
Kuehl, Michael
Huang, Jing
Landgren, Ola
Mock, Beverly
TI Systems pharmacogenomics approach identifies synergistic molecular
action of combined MTOR/HDAC inhibition on MYC
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 105th Annual Meeting of the American-Association-for-Cancer-Research
(AACR)
CY APR 05-09, 2014
CL San Diego, CA
SP Amer Assoc Canc Res
C1 [Gamache, Benjamin J.; Simmons, John K.; Michalowski, Aleksandra; Patel, Jyoti; Zhang, Ke; Zhang, Shuling; DuBois, Wendy; Zingone, Adriana; Kuehl, Michael; Huang, Jing; Landgren, Ola; Mock, Beverly] NCI, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD OCT 1
PY 2014
VL 74
IS 19
SU S
MA 5472
DI 10.1158/1538-7445.AM2014-5472
PG 1
WC Oncology
SC Oncology
GA CB8VR
UT WOS:000349910204390
ER
PT J
AU Gameiro, SR
Jammeh, ML
Wattenberg, MM
Tsang, KY
Ferrone, S
Hodge, JW
AF Gameiro, Sofia R.
Jammeh, Momodou L.
Wattenberg, Max M.
Tsang, Kwong Y.
Ferrone, Soldano
Hodge, James W.
TI Radiation-induced immunogenic modulation of tumor enhances antigen
processing and calreticulin exposure, resulting in enhanced T-cell
killing
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 105th Annual Meeting of the American-Association-for-Cancer-Research
(AACR)
CY APR 05-09, 2014
CL San Diego, CA
SP Amer Assoc Canc Res
C1 [Gameiro, Sofia R.; Jammeh, Momodou L.; Wattenberg, Max M.; Tsang, Kwong Y.; Hodge, James W.] NCI CCR, Bethesda, MD USA.
[Ferrone, Soldano] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD OCT 1
PY 2014
VL 74
IS 19
SU S
MA 632
DI 10.1158/1538-7445.AM2014-632
PG 1
WC Oncology
SC Oncology
GA CB8UN
UT WOS:000349906905094
ER
PT J
AU Gangjee, A
Xiang, WG
Mooberry, SL
Hamel, E
AF Gangjee, Aleem
Xiang, Weiguo
Mooberry, Susan L.
Hamel, Ernest
TI Potent antitubulin and antitumor activities influenced by the 3-D
conformational shape of bicyclic fused pyrimidines
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 105th Annual Meeting of the American-Association-for-Cancer-Research
(AACR)
CY APR 05-09, 2014
CL San Diego, CA
SP Amer Assoc Canc Res
C1 [Gangjee, Aleem; Xiang, Weiguo] Duquesne Univ, Pittsburgh, PA 15219 USA.
[Mooberry, Susan L.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA.
[Hamel, Ernest] NCI, Frederick, MD 21701 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD OCT 1
PY 2014
VL 74
IS 19
SU S
MA 836
DI 10.1158/1538-7445.AM2014-836
PG 1
WC Oncology
SC Oncology
GA CB8UN
UT WOS:000349906905295
ER
PT J
AU Gangjee, A
Pavana, RK
Ihnat, M
Hamel, E
AF Gangjee, Aleem
Pavana, Roheeth K.
Ihnat, Michael
Hamel, Ernest
TI Design and preclinical evaluation of single agents with tubulin and
multiple receptor tyrosine kinase inhibition
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 105th Annual Meeting of the American-Association-for-Cancer-Research
(AACR)
CY APR 05-09, 2014
CL San Diego, CA
SP Amer Assoc Canc Res
C1 [Gangjee, Aleem; Pavana, Roheeth K.] Duquesne Univ, Div Med Chem, Grad Sch Pharmaceut Sci, Pittsburgh, PA 15219 USA.
[Ihnat, Michael] Univ Oklahoma, Coll Pharm, Dept Pharmaceut Sci, Oklahoma City, OK USA.
[Hamel, Ernest] NCI, Screening Technol Branch, Dev Therapeut Program, Div Canc Treatment & Diag,Frederick Natl Lab Canc, Frederick, MD 21701 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD OCT 1
PY 2014
VL 74
IS 19
SU S
MA 1622
DI 10.1158/1538-7445.AM2014-1622
PG 1
WC Oncology
SC Oncology
GA CB8UN
UT WOS:000349906901345
ER
PT J
AU Gharwan, H
Jones, T
Tang, W
Ambs, S
Prokunina, L
Caplen, N
AF Gharwan, Helen
Jones, Tamara
Tang, Wei
Ambs, Stefan
Prokunina, Ludmilla
Caplen, Natasha
TI Analysis of JAZF1 loss-of-function reveals its role in regulation of
genes relevant for prostate cancer
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 105th Annual Meeting of the American-Association-for-Cancer-Research
(AACR)
CY APR 05-09, 2014
CL San Diego, CA
SP Amer Assoc Canc Res
C1 [Gharwan, Helen; Jones, Tamara; Tang, Wei; Ambs, Stefan; Prokunina, Ludmilla; Caplen, Natasha] NCI, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 2
U2 2
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD OCT 1
PY 2014
VL 74
IS 19
SU S
MA LB-87
DI 10.1158/1538-7445.AM2014-LB-87
PG 1
WC Oncology
SC Oncology
GA CB8VR
UT WOS:000349910205422
ER
PT J
AU Giles, AJ
Murgai, M
Vicioso, Y
Highfil, S
Mackall, C
Wexler, L
Lyden, D
Kaplan, RN
AF Giles, Amber J.
Murgai, Meera
Vicioso, Yorleny
Highfil, Steven
Mackall, Crystal
Wexler, Leonard
Lyden, David
Kaplan, Rosandra Natasha
TI Bone marrow hematopoietic stem cell niche activation and mobilization
fosters the metastatic niche
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 105th Annual Meeting of the American-Association-for-Cancer-Research
(AACR)
CY APR 05-09, 2014
CL San Diego, CA
SP Amer Assoc Canc Res
C1 [Giles, Amber J.; Murgai, Meera; Vicioso, Yorleny; Highfil, Steven; Mackall, Crystal; Kaplan, Rosandra Natasha] NCI, Bethesda, MD 20892 USA.
[Wexler, Leonard] Mem Sloan Kettering Canc Ctr, New York, NY USA.
[Lyden, David] Weill Cornell Med Ctr, New York, NY USA.
NR 0
TC 0
Z9 0
U1 1
U2 2
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD OCT 1
PY 2014
VL 74
IS 19
SU S
MA 3058
DI 10.1158/1538-7445.AM2014-3058
PG 1
WC Oncology
SC Oncology
GA CB8VR
UT WOS:000349910200065
ER
PT J
AU Giovannetti, E
Wang, QY
Funel, N
Avan, A
Lagerweij, T
Caretti, V
Boggi, U
Wang, Y
Caponi, S
van der Velde, A
Vasile, E
Verheul, HM
Wurdinger, T
Giaccone, G
AF Giovannetti, Elisa
Wang, Qiuyan
Funel, Niccola
Avan, Amir
Lagerweij, Tonny
Caretti, Viola
Boggi, Ugo
Wang, Yisong
Caponi, Sara
van der Velde, Arjan
Vasile, Enrico
Verheul, Henk M.
Wurdinger, Thomas
Giaccone, Giuseppe
TI Modulation of autophagy and oncogenic phenotypes through CYB5A-TRAF6
signaling influence prognosis of resected and metastatic pancreatic
cancer
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 105th Annual Meeting of the American-Association-for-Cancer-Research
(AACR)
CY APR 05-09, 2014
CL San Diego, CA
SP Amer Assoc Canc Res
C1 [Giovannetti, Elisa; Avan, Amir; Lagerweij, Tonny; van der Velde, Arjan; Verheul, Henk M.; Wurdinger, Thomas] Vrije Univ Amsterdam Med Ctr, Amsterdam, Netherlands.
[Wang, Qiuyan] NCI, NIH, Bethesda, MD 20892 USA.
[Funel, Niccola; Boggi, Ugo; Caponi, Sara; Vasile, Enrico] Univ Pisa, Pisa, Italy.
[Caretti, Viola] Stanford Univ, Stanford, CA 94305 USA.
[Wang, Yisong; Giaccone, Giuseppe] Georgetown Univ, Washington, DC USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD OCT 1
PY 2014
VL 74
IS 19
SU S
MA 2787
DI 10.1158/1538-7445.AM2014-2787
PG 2
WC Oncology
SC Oncology
GA CB8UN
UT WOS:000349906904045
ER
PT J
AU Gong, J
Hutter, C
Chang-Claude, J
Newcomb, P
Berndt, S
Brenner, H
Chan, AT
Marchand, LL
Harrison, T
Lin, Y
Slattery, ML
White, E
Potter, J
Jiao, S
Lemire, M
Hsu, L
Peters, U
AF Gong, Jian
Hutter, Carolyn
Chang-Claude, Jenny
Newcomb, Polly
Berndt, Sonja
Brenner, Hermann
Chan, Andrew T.
Marchand, Loic L.
Harrison, Tabitha
Lin, Yi
Slattery, Martha L.
White, Emily
Potter, John
Jiao, Shuo
Lemire, Mathieu
Hsu, Li
Peters, Ulrike
TI Genome-wide interaction analyses between genetic variants and alcohol
consumption and risk of colorectal cancer
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 105th Annual Meeting of the American-Association-for-Cancer-Research
(AACR)
CY APR 05-09, 2014
CL San Diego, CA
SP Amer Assoc Canc Res
C1 [Gong, Jian; Newcomb, Polly; Harrison, Tabitha; Lin, Yi; White, Emily; Potter, John; Jiao, Shuo; Hsu, Li; Peters, Ulrike] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
[Hutter, Carolyn] NHGRI, Bethesda, MD 20892 USA.
[Chang-Claude, Jenny; Brenner, Hermann] German Canc Res Ctr, Heidelberg, Germany.
[Berndt, Sonja] NCI, Bethesda, MD 20892 USA.
[Chan, Andrew T.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Chan, Andrew T.] Harvard Univ, Sch Med, Boston, MA USA.
[Marchand, Loic L.] Univ Hawaii, Ctr Canc, Honolulu, HI 96822 USA.
[Slattery, Martha L.] Univ Utah, Hlth Sci Ctr, Salt Lake City, UT USA.
[Lemire, Mathieu] Ontario Inst Canc Res, Toronto, ON, Canada.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD OCT 1
PY 2014
VL 74
IS 19
SU S
MA 2195
DI 10.1158/1538-7445.AM2014-2195
PG 2
WC Oncology
SC Oncology
GA CB8UN
UT WOS:000349906902406
ER
PT J
AU Greer, YE
Gao, B
Yang, YZ
Rubin, JS
AF Greer, Yoshimi Endo
Gao, Bo
Yang, Yingzi
Rubin, Jeffrey S.
TI Lack of casein kinase 1 delta induces DNA damage, inhibition of mTORC1
signaling and nucleophagy
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 105th Annual Meeting of the American-Association-for-Cancer-Research
(AACR)
CY APR 05-09, 2014
CL San Diego, CA
SP Amer Assoc Canc Res
C1 [Greer, Yoshimi Endo; Rubin, Jeffrey S.] NCI, NIH, Bethesda, MD 20892 USA.
[Gao, Bo; Yang, Yingzi] NHGRI, NIH, Bethesda, MD 20892 USA.
NR 0
TC 1
Z9 1
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD OCT 1
PY 2014
VL 74
IS 19
SU S
MA 1335
DI 10.1158/1538-7445.AM2014-1335
PG 1
WC Oncology
SC Oncology
GA CB8UN
UT WOS:000349906901067
ER
PT J
AU Grenga, I
Ascierto, ML
Donahue, RN
Gulley, JL
Heery, CR
Madan, RA
Schlom, J
Wang, E
Farsaci, B
AF Grenga, Italia
Ascierto, Maria Libera
Donahue, Renee N.
Gulley, James L.
Heery, Christopher R.
Madan, Ravi A.
Schlom, Jeffrey
Wang, Ena
Farsaci, Benedetto
TI Identification of immune signatures predicting for clinical outcome
measured by flow-cytometry and immunogenetic analysis of PBMCs from
breast cancer patients treated with docetaxel alone or docetaxel plus
vaccine
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 105th Annual Meeting of the American-Association-for-Cancer-Research
(AACR)
CY APR 05-09, 2014
CL San Diego, CA
SP Amer Assoc Canc Res
C1 [Grenga, Italia; Donahue, Renee N.; Gulley, James L.; Heery, Christopher R.; Madan, Ravi A.; Schlom, Jeffrey; Farsaci, Benedetto] NCI, NIH, Ctr Canc Res, Lab Tumor Immunol & Biol, Bethesda, MD 20892 USA.
[Ascierto, Maria Libera; Wang, Ena] NIH, Ctr Clin, Bethesda, MD 20892 USA.
[Ascierto, Maria Libera; Wang, Ena] FOCIS Ctr Excellence, Dept Transfus Med, Infect Desease & Immunogenet Sect, Bethesda, MD USA.
RI Farsaci, Benedetto/L-9837-2014; Gulley, James/K-4139-2016
OI Farsaci, Benedetto/0000-0001-8275-2561; Gulley,
James/0000-0002-6569-2912
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD OCT 1
PY 2014
VL 74
IS 19
SU S
MA 2544
DI 10.1158/1538-7445.AM2014-2544
PG 2
WC Oncology
SC Oncology
GA CB8UN
UT WOS:000349906903282
ER
PT J
AU Gu, F
Han, JL
Hankinson, S
Schernhammer, E
AF Gu, Fangyi
Han, Jiali
Hankinson, Sue
Schernhammer, Eva
CA Nurses' Hlth Study Grp
TI Rotating night shift work and cancer mortality in the nurses' health
study
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 105th Annual Meeting of the American-Association-for-Cancer-Research
(AACR)
CY APR 05-09, 2014
CL San Diego, CA
SP Amer Assoc Canc Res
C1 [Gu, Fangyi] NCI DCEG, Rockville, MD USA.
[Han, Jiali] Indiana Univ, Indianapolis, IN 46204 USA.
[Hankinson, Sue] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Hankinson, Sue] Harvard Univ, Sch Med, Boston, MA USA.
[Schernhammer, Eva] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
NR 0
TC 1
Z9 1
U1 1
U2 1
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD OCT 1
PY 2014
VL 74
IS 19
SU S
MA 2178
DI 10.1158/1538-7445.AM2014-2178
PG 2
WC Oncology
SC Oncology
GA CB8UN
UT WOS:000349906902389
ER
PT J
AU Gus-Brautbar, Y
Casper, J
Bielenberg, DR
Cheng, J
Schmidt, B
Hammock, BD
Zeldin, DC
Kieran, MW
Panigrahy, D
AF Gus-Brautbar, Yael
Casper, Jessica
Bielenberg, Diane R.
Cheng, Jennifer
Schmidt, Birgitta
Hammock, Bruce D.
Zeldin, Darryl C.
Kieran, Mark W.
Panigrahy, Dipak
TI The eicosanoid 20-HETE triggers Ras activation, pancreatic cancer growth
and metastasis through inflammatory macrophage signaling
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 105th Annual Meeting of the American-Association-for-Cancer-Research
(AACR)
CY APR 05-09, 2014
CL San Diego, CA
SP Amer Assoc Canc Res
C1 [Gus-Brautbar, Yael; Casper, Jessica; Panigrahy, Dipak] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Ctr Vasc Biol Res, Boston, MA 02215 USA.
[Gus-Brautbar, Yael; Casper, Jessica; Panigrahy, Dipak] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Pathol, Boston, MA 02215 USA.
[Bielenberg, Diane R.] Harvard Univ, Sch Med, Boston Childrens Hosp, Vasc Biol Program, Boston, MA USA.
[Cheng, Jennifer; Zeldin, Darryl C.] NIEHS, Lab Resp Biol, NIH, Res Triangle Pk, NC 27709 USA.
[Schmidt, Birgitta] Harvard Univ, Sch Med, Dept Pathol, Boston Childrens Hosp, Boston, MA 02115 USA.
[Hammock, Bruce D.] Univ Calif Davis, Dept Entomol, Davis, CA USA.
[Hammock, Bruce D.] Univ Calif Davis, Canc Res Ctr, Davis, CA USA.
[Kieran, Mark W.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Pediat Oncol, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD OCT 1
PY 2014
VL 74
IS 19
SU S
MA 4833
DI 10.1158/1538-7445.AM2014-4833
PG 2
WC Oncology
SC Oncology
GA CB8VR
UT WOS:000349910203302
ER
PT J
AU Gwilliam, JC
CVitan, A
Watson, N
Falkenberg, L
Yousefi, N
Alexander, H
Morin, A
Wiest, JS
DeCicco-Skinner, KL
AF Gwilliam, J. Curtis
CVitan, Alexander
Watson, Nicholas
Falkenberg, Lauren
Yousefi, Nyousha
Alexander, Hepzibha
Morin, Adam
Wiest, Jonathan S.
DeCicco-Skinner, Katie L.
TI Fibroblast influence on keratinocyte tumorigenic and metastatic
potential in cutaneous squamous cell carcinoma
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 105th Annual Meeting of the American-Association-for-Cancer-Research
(AACR)
CY APR 05-09, 2014
CL San Diego, CA
SP Amer Assoc Canc Res
C1 [Gwilliam, J. Curtis; CVitan, Alexander; Watson, Nicholas; Falkenberg, Lauren; Yousefi, Nyousha; Alexander, Hepzibha; Morin, Adam; DeCicco-Skinner, Katie L.] Amer Univ, Washington, DC 20016 USA.
[Wiest, Jonathan S.] NCI, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD OCT 1
PY 2014
VL 74
IS 19
SU S
MA 3609
DI 10.1158/1538-7445.AM2014-3609
PG 1
WC Oncology
SC Oncology
GA CB8VR
UT WOS:000349910201105
ER
PT J
AU Han, Y
Signorello, LB
Strom, SS
Kittles, RA
Rybicki, BA
Stanford, JL
Goodman, PJ
Berndt, SI
Carpten, J
Casey, G
Chu, L
Conti, DV
Rand, KA
Diver, R
Hennis, AJ
John, EM
Kibel, AS
Klein, EA
Kolb, S
Marchand, LL
Leske, MC
Murphy, AB
Neslund-Dudas, C
Park, JY
Pettaway, CA
Rebbeck, TR
Gapstur, SM
Zheng, SL
Wu, SY
Witte, JS
Xu, JF
Isaacs, WB
Ingles, SA
Hsing, AW
Easton, DF
Eeles, RA
Schumacher, FR
Chanock, SJ
Nemesure, B
Blot, WJ
Stram, DO
Henderson, BE
Haiman, CA
AF Han, Ying
Signorello, Lisa B.
Strom, Sara S.
Kittles, Rick A.
Rybicki, Benjamin A.
Stanford, Janet L.
Goodman, Phyllis J.
Berndt, Sonja I.
Carpten, John
Casey, Graham
Chu, Lisa
Conti, David V.
Rand, Kristin A.
Diver, Ryan
Hennis, Anselm J.
John, Esther M.
Kibel, Adam S.
Klein, Eric A.
Kolb, Suzanne
Marchand, Loic L.
Leske, M. Cristina
Murphy, Adam B.
Neslund-Dudas, Christine
Park, Jong Y.
Pettaway, Curtis A.
Rebbeck, Timothy R.
Gapstur, Susan M.
Zheng, Siqun Lilly
Wu, Suh-Yuh
Witte, John S.
Xu, Jianfeng
Isaacs, William B.
Ingles, Sue A.
Hsing, Ann W.
Easton, Douglas F.
Eeles, Rosalind A.
Schumacher, Fredrick R.
Chanock, Stephen J.
Nemesure, Barbara
Blot, William J.
Stram, Daniel O.
Henderson, Brian E.
Haiman, Christopher A.
CA PRACTICAL Consortium
ELLIPSE GAME-ON Consortium
TI Generalizability of established prostate cancer risk variants in men of
African ancestry
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 105th Annual Meeting of the American-Association-for-Cancer-Research
(AACR)
CY APR 05-09, 2014
CL San Diego, CA
SP Amer Assoc Canc Res
C1 [Han, Ying; Casey, Graham; Conti, David V.; Rand, Kristin A.; Ingles, Sue A.; Schumacher, Fredrick R.; Stram, Daniel O.; Henderson, Brian E.; Haiman, Christopher A.] Univ So Calif, Los Angeles, CA USA.
[Signorello, Lisa B.] Harvard Univ, Sch Publ Hlth, Cambridge, MA 02138 USA.
[Strom, Sara S.; Pettaway, Curtis A.] Univ Texas MD Anderson Canc Ctr, Houston, TX USA.
[Kittles, Rick A.] Univ Illinois, Chicago, IL USA.
[Rybicki, Benjamin A.; Neslund-Dudas, Christine] Henry Ford Hosp, Detroit, MI USA.
[Stanford, Janet L.; Kolb, Suzanne] Fred Hutchinson Canc Res Ctr, Seattle, WA USA.
[Goodman, Phyllis J.] SWOG Stat Ctr, Seattle, WA USA.
[Berndt, Sonja I.; Chanock, Stephen J.] NIH, Bethesda, MD USA.
[Carpten, John] Translat Genom Res Inst, Phoenix, AZ USA.
[Chu, Lisa; John, Esther M.; Hsing, Ann W.] Canc Prevent Inst Calif, Fremont, CA USA.
[Diver, Ryan; Gapstur, Susan M.] Amer Canc Soc, Atlanta, GA 30329 USA.
[Hennis, Anselm J.; Leske, M. Cristina; Wu, Suh-Yuh; Nemesure, Barbara] SUNY Stony Brook, Stony Brook, NY USA.
[Kibel, Adam S.] Dana Farber Canc Inst, Boston, MA USA.
[Klein, Eric A.] Cleveland Clin, Cleveland, OH USA.
[Marchand, Loic L.] Univ Hawaii, Ctr Canc, Honolulu, HI 96822 USA.
[Murphy, Adam B.] Northwestern Univ, Evanston, IL 60208 USA.
[Park, Jong Y.] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA.
[Rebbeck, Timothy R.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA.
[Rebbeck, Timothy R.] Abramson Canc Ctr, Philadelphia, PA USA.
[Zheng, Siqun Lilly; Xu, Jianfeng] Wake Forest Univ, Sch Med, Winston Salem, NC 27109 USA.
[Witte, John S.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Isaacs, William B.] Johns Hopkins Hosp & Med Inst, Baltimore, MD USA.
[Easton, Douglas F.] Univ Cambridge, Cambridge CB2 1TN, England.
[Blot, William J.] Vanderbilt Univ, Sch Med, Nashville, TN USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD OCT 1
PY 2014
VL 74
IS 19
SU S
MA 5066
DI 10.1158/1538-7445.AM2014-5066
PG 2
WC Oncology
SC Oncology
GA CB8VR
UT WOS:000349910204021
ER
PT J
AU Han, Y
Love, SA
Bush, WS
Campa, D
Butler, AM
Dumitrescu, L
Tsilidis, K
Cheng, I
Wilkens, LR
Fowke, JH
Ambite, JL
Buyske, S
Park, SL
Haiman, CA
Marchand, LL
Hindorff, LA
Canzian, F
Schumacher, FR
AF Han, Ying
Love, Shelly-Ann
Bush, William S.
Campa, Daniele
Butler, Anne M.
Dumitrescu, Logan
Tsilidis, Konstantinos
Cheng, Iona
Wilkens, Lynne R.
Fowke, Jay H.
Ambite, Jose Luis
Buyske, Steve
Park, S. Lani
Haiman, Christopher A.
Marchand, Loic L.
Hindorff, Lucia A.
Canzian, Federico
Schumacher, Fredrick R.
CA PRACTICAL Consortium
BPC3 Consortium
TI Pleiotropy analysis identifies a novel prostate cancer variant at
6p21.33: The PAGE, PRACTICAL, and BPC3 Consortia
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 105th Annual Meeting of the American-Association-for-Cancer-Research
(AACR)
CY APR 05-09, 2014
CL San Diego, CA
SP Amer Assoc Canc Res
C1 [Han, Ying; Ambite, Jose Luis; Park, S. Lani; Haiman, Christopher A.; Schumacher, Fredrick R.] Univ So Calif, Los Angeles, CA 90089 USA.
[Love, Shelly-Ann; Butler, Anne M.] Univ N Carolina, Chapel Hill, NC 27515 USA.
[Bush, William S.; Dumitrescu, Logan; Fowke, Jay H.] Vanderbilt Univ, Nashville, TN USA.
[Campa, Daniele; Canzian, Federico] German Canc Res Ctr, Heidelberg, Germany.
[Tsilidis, Konstantinos] Univ Ioannina, Sch Med, GR-45110 Ioannina, Greece.
[Cheng, Iona] Canc Prevent Inst Calif, Fremont, CA USA.
[Wilkens, Lynne R.; Marchand, Loic L.] Univ Hawaii, Ctr Canc, Honolulu, HI 96822 USA.
[Buyske, Steve] Rutgers State Univ, Piscataway, NJ 08855 USA.
[Hindorff, Lucia A.] NIH, Bethesda, MD USA.
RI Campa, Daniele/K-1617-2016
OI Campa, Daniele/0000-0003-3220-9944
NR 0
TC 0
Z9 0
U1 1
U2 1
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD OCT 1
PY 2014
VL 74
IS 19
SU S
MA 5064
DI 10.1158/1538-7445.AM2014-5064
PG 2
WC Oncology
SC Oncology
GA CB8VR
UT WOS:000349910204019
ER
PT J
AU Harlid, SS
Xu, ZL
Panduri, V
Sandler, DP
Taylor, JA
AF Harlid, Sara Sophia
Xu, Zongli
Panduri, Vijayalakshmi
Sandler, Dale P.
Taylor, Jack A.
TI Epigenome-wide study of sister study samples replicates and extends cpg
sites associated with cigarette smoking
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 105th Annual Meeting of the American-Association-for-Cancer-Research
(AACR)
CY APR 05-09, 2014
CL San Diego, CA
SP Amer Assoc Canc Res
C1 [Harlid, Sara Sophia; Xu, Zongli; Panduri, Vijayalakshmi; Sandler, Dale P.; Taylor, Jack A.] NIEHS, NIH, Res Triangle Pk, NC 27709 USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD OCT 1
PY 2014
VL 74
IS 19
SU S
MA 284
DI 10.1158/1538-7445.AM2014-284
PG 2
WC Oncology
SC Oncology
GA CB8UN
UT WOS:000349906904101
ER
PT J
AU He, YL
Jiang, SL
Dubois, W
Ren, L
Khanna, C
Huang, J
AF He, Yunlong
Jiang, Shunlin
Dubois, Wendy
Ren, Ling
Khanna, Chand
Huang, Jing
TI A p53 and microRNA-mediated pathway regulates mesenchymal stem cell
differentiation
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 105th Annual Meeting of the American-Association-for-Cancer-Research
(AACR)
CY APR 05-09, 2014
CL San Diego, CA
SP Amer Assoc Canc Res
C1 [He, Yunlong; Jiang, Shunlin; Dubois, Wendy; Ren, Ling; Khanna, Chand; Huang, Jing] NCI, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD OCT 1
PY 2014
VL 74
IS 19
SU S
MA 2468
DI 10.1158/1538-7445.AM2014-2468
PG 1
WC Oncology
SC Oncology
GA CB8UN
UT WOS:000349906903199
ER
PT J
AU House, CD
Annunziata, CM
AF House, Carrie D.
Annunziata, Christina M.
TI NF-kappa B signaling supports a sub-population of ovarian cancer
tumor-initiating cells
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 105th Annual Meeting of the American-Association-for-Cancer-Research
(AACR)
CY APR 05-09, 2014
CL San Diego, CA
SP Amer Assoc Canc Res
C1 [House, Carrie D.; Annunziata, Christina M.] NCI, Bethesda, MD 20892 USA.
RI Annunziata, Christina/L-3219-2016
OI Annunziata, Christina/0000-0003-2033-6532
NR 0
TC 0
Z9 0
U1 0
U2 1
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD OCT 1
PY 2014
VL 74
IS 19
SU S
MA 1923
DI 10.1158/1538-7445.AM2014-1923
PG 2
WC Oncology
SC Oncology
GA CB8UN
UT WOS:000349906902138
ER
PT J
AU Hsu, L
Jeon, J
Brenner, H
Berndt, S
Chan, AT
Chang-Claude, J
Gruber, SB
Harrison, T
Hoffmeister, M
Newcomb, P
Potter, J
Schumacher, F
Slattery, M
Thomas, D
White, E
Zheng, YY
Peters, U
AF Hsu, Li
Jeon, Jihyoun
Brenner, Hermann
Berndt, Sonja
Chan, Andrew T.
Chang-Claude, Jenny
Gruber, Stephen B.
Harrison, Tabitha
Hoffmeister, Michael
Newcomb, Polly
Potter, John
Schumacher, Fredrick
Slattery, Martha
Thomas, Duncan
White, Emily
Zheng, Yingye
Peters, Ulrike
CA Colorectal Transdisciplinary Study
Genetics Epidemiology Colorectal
TI Assessing colorectal cancer risk using known genetic susceptibility
variants and family history accounting for endoscopy
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 105th Annual Meeting of the American-Association-for-Cancer-Research
(AACR)
CY APR 05-09, 2014
CL San Diego, CA
SP Amer Assoc Canc Res
C1 [Hsu, Li; Jeon, Jihyoun; Harrison, Tabitha; Newcomb, Polly; Potter, John; White, Emily; Zheng, Yingye; Peters, Ulrike] Fred Hutchinson Canc Res Ctr, Publ Hlth Sci Div, Seattle, WA 98104 USA.
[Brenner, Hermann; Hoffmeister, Michael] German Canc Res Ctr, Div Clin Epidemiol & Aging Res, Heidelberg, Germany.
[Berndt, Sonja] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Chan, Andrew T.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA.
[Chan, Andrew T.] Harvard Univ, Sch Med, Boston, MA USA.
[Chan, Andrew T.] Brigham & Womens Hosp, Channing Div Network Med, Boston, MA 02115 USA.
[Chang-Claude, Jenny] German Canc Res Ctr, Dept Canc Epidemiol, Heidelberg, Germany.
[Gruber, Stephen B.] Univ So Calif, USC Norris Comprehens Canc Ctr, Los Angeles, CA USA.
[Potter, John] Massey Univ, Ctr Publ Hlth Res, Wellington, New Zealand.
[Schumacher, Fredrick; Thomas, Duncan] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA.
[Slattery, Martha] Univ Utah, Dept Internal Med, Hlth Sci Ctr, Salt Lake City, UT 84112 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD OCT 1
PY 2014
VL 74
IS 19
SU S
MA 2921
DI 10.1158/1538-7445.AM2014-2921
PG 2
WC Oncology
SC Oncology
GA CB8UN
UT WOS:000349906904190
ER
PT J
AU Hu, W
Landgren, O
Bassig, B
Purdue, M
Engels, E
Lan, Q
Rothman, N
AF Hu, Wei
Landgren, Ola
Bassig, Bryan
Purdue, Mark
Engels, Eric
Lan, Qing
Rothman, Nathaniel
TI Elevated serum free light chains and risk of non-Hodgkin lymphoma and
the subtype follicular lymphoma in a prospective cohort study
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 105th Annual Meeting of the American-Association-for-Cancer-Research
(AACR)
CY APR 05-09, 2014
CL San Diego, CA
SP Amer Assoc Canc Res
C1 [Hu, Wei; Landgren, Ola; Bassig, Bryan; Purdue, Mark; Engels, Eric; Lan, Qing; Rothman, Nathaniel] NCI, Rockville, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD OCT 1
PY 2014
VL 74
IS 19
SU S
MA 5074
DI 10.1158/1538-7445.AM2014-5074
PG 1
WC Oncology
SC Oncology
GA CB8VR
UT WOS:000349910204029
ER
PT J
AU Hua, X
Landi, TM
Shi, JX
AF Hua, Xing
Landi, Teresa Maria
Shi, Jianxin
TI Detecting driver genes based on tumor whole-exome sequencing studies
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 105th Annual Meeting of the American-Association-for-Cancer-Research
(AACR)
CY APR 05-09, 2014
CL San Diego, CA
SP Amer Assoc Canc Res
C1 [Hua, Xing; Landi, Teresa Maria; Shi, Jianxin] NCI, Rockville, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD OCT 1
PY 2014
VL 74
IS 19
SU S
MA 2372
DI 10.1158/1538-7445.AM2014-2372
PG 1
WC Oncology
SC Oncology
GA CB8UN
UT WOS:000349906903097
ER
PT J
AU Huang, WY
Su, LJ
Johnson, CC
Purdue, MP
Berndt, SI
AF Huang, Wen-Yi
Su, L. Joseph
Johnson, Christine C.
Purdue, Mark P.
Berndt, Sonja I.
TI A prospective study of non-steroidal anti-inflammatory drug use and
colorectal adenoma and colorectal cancer
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 105th Annual Meeting of the American-Association-for-Cancer-Research
(AACR)
CY APR 05-09, 2014
CL San Diego, CA
SP Amer Assoc Canc Res
C1 [Huang, Wen-Yi; Purdue, Mark P.; Berndt, Sonja I.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Su, L. Joseph] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Johnson, Christine C.] Henry Ford Hosp, Josephine Ford Canc Ctr, Detroit, MI 48202 USA.
RI Purdue, Mark/C-9228-2016
OI Purdue, Mark/0000-0003-1177-3108
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD OCT 1
PY 2014
VL 74
IS 19
SU S
MA 2159
DI 10.1158/1538-7445.AM2014-2159
PG 2
WC Oncology
SC Oncology
GA CB8UN
UT WOS:000349906902371
ER
PT J
AU Hyland, PL
Zhang, H
Yang, Q
Lin, SW
Maeder, D
Hu, N
Tang, ZZ
Su, H
Wang, LM
Wang, CY
Ding, T
Fan, JH
Qiao, YL
Wheeler, W
Giffen, C
Burdett, L
Wang, ZM
Chanock, SJ
Dawsey, SM
Freedman, ND
Abnet, CC
Goldstein, AM
Yu, K
Taylor, PR
AF Hyland, Paula L.
Zhang, Han
Yang, Qi
Lin, Shih-Wen
Maeder, Dennis
Hu, Nan
Tang, Ze-Zhong
Su, Hua
Wang, Lemin
Wang, Chaoyu
Ding, Ti
Fan, Jin-Hu
Qiao, You-Lin
Wheeler, William
Giffen, Carol
Burdett, Laurie
Wang, Zhaoming
Chanock, Stephen J.
Dawsey, Sanford M.
Freedman, Neal D.
Abnet, Christian C.
Goldstein, Alisa M.
Yu, Kai
Taylor, Philip R.
TI Pathway analysis of genome-wide association study data highlights taste
transduction and metabolic pathways and esophageal squamous cell
carcinoma susceptibility
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 105th Annual Meeting of the American-Association-for-Cancer-Research
(AACR)
CY APR 05-09, 2014
CL San Diego, CA
SP Amer Assoc Canc Res
C1 [Hyland, Paula L.; Zhang, Han; Yang, Qi; Lin, Shih-Wen; Maeder, Dennis; Hu, Nan; Su, Hua; Wang, Lemin; Wang, Chaoyu; Burdett, Laurie; Wang, Zhaoming; Chanock, Stephen J.; Dawsey, Sanford M.; Freedman, Neal D.; Abnet, Christian C.; Goldstein, Alisa M.; Yu, Kai; Taylor, Philip R.] NCI, NIH, Bethesda, MD 20892 USA.
[Tang, Ze-Zhong; Ding, Ti] Shanxi Canc Hosp, Taiyuan, Peoples R China.
[Fan, Jin-Hu; Qiao, You-Lin] Chinese Acad Med Sci, Beijing 100730, Peoples R China.
[Wheeler, William; Giffen, Carol] Informat Management Serv Inc, Silver Spring, MD USA.
RI Abnet, Christian/C-4111-2015
OI Abnet, Christian/0000-0002-3008-7843
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD OCT 1
PY 2014
VL 74
IS 19
SU S
MA 2203
DI 10.1158/1538-7445.AM2014-2203
PG 2
WC Oncology
SC Oncology
GA CB8UN
UT WOS:000349906902414
ER
PT J
AU Illuzzi, J
Harris, NA
Manvilla, BA
Kim, D
Li, MX
Drohat, AC
Wilson, DM
AF Illuzzi, Jennifer
Harris, Nicole A.
Manvilla, Brittney A.
Kim, Daemyung
Li, Mengxia
Drohat, Alexander C.
Wilson, David M.
TI Deciphering the role of APE1 protein variants in disease etiology
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 105th Annual Meeting of the American-Association-for-Cancer-Research
(AACR)
CY APR 05-09, 2014
CL San Diego, CA
SP Amer Assoc Canc Res
C1 [Illuzzi, Jennifer; Li, Mengxia; Wilson, David M.] NIH, Baltimore, MD USA.
[Harris, Nicole A.] Sanford Burnham Med Res Inst, Orlando, FL USA.
[Manvilla, Brittney A.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA.
[Kim, Daemyung] Cheongju Univ, Cheongju, South Korea.
[Drohat, Alexander C.] Univ Maryland, Sch Med, Marlene & Stewart Greenebaum Canc Ctr, Baltimore, MD 21201 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD OCT 1
PY 2014
VL 74
IS 19
SU S
MA 2388
DI 10.1158/1538-7445.AM2014-2388
PG 1
WC Oncology
SC Oncology
GA CB8UN
UT WOS:000349906903113
ER
PT J
AU Ishida, M
Kagawa, S
Shimoyama, K
Takehara, K
Noma, K
Tanabe, S
Tazawa, H
Matsuoka, J
Kobayashi, H
Fujiwara, T
AF Ishida, Michihiro
Kagawa, Shunsuke
Shimoyama, Kyoko
Takehara, Kiyoto
Noma, Kazuhiro
Tanabe, Shunsuke
Tazawa, Hiroshi
Matsuoka, Junji
Kobayashi, Hisataka
Fujiwara, Toshiyoshi
TI Novel combination therapy of adenoviral gene transfer of
HER2-extracellular domain and trastuzumab-based photoimmunotherapy for
HER2 negative cancer cells
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 105th Annual Meeting of the American-Association-for-Cancer-Research
(AACR)
CY APR 05-09, 2014
CL San Diego, CA
SP Amer Assoc Canc Res
C1 [Ishida, Michihiro; Kagawa, Shunsuke; Shimoyama, Kyoko; Takehara, Kiyoto; Noma, Kazuhiro; Tanabe, Shunsuke; Fujiwara, Toshiyoshi] Okayama Univ, Grad Sch, Dept Gastroenterol Surg, Okayama, Japan.
[Tazawa, Hiroshi] Okayama Univ Hosp, Ctr Innovat Clin Med, Okayama, Japan.
[Matsuoka, Junji] Okayama Univ Hosp, Dept Palliat Care, Okayama, Japan.
[Kobayashi, Hisataka] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 1
U2 2
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD OCT 1
PY 2014
VL 74
IS 19
SU S
MA 2615
DI 10.1158/1538-7445.AM2014-2615
PG 1
WC Oncology
SC Oncology
GA CB8UN
UT WOS:000349906903360
ER
PT J
AU Izhak, L
Kato, S
Parish, ST
Terabe, M
Berzofsky, JA
AF Izhak, Liat
Kato, Shingo
Parish, Stanley T.
Terabe, Masaki
Berzofsky, Jay A.
TI Cross-regulation between the two subsets of NKT cells is dependent on
interferon-gamma
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 105th Annual Meeting of the American-Association-for-Cancer-Research
(AACR)
CY APR 05-09, 2014
CL San Diego, CA
SP Amer Assoc Canc Res
C1 [Izhak, Liat; Kato, Shingo; Parish, Stanley T.; Terabe, Masaki; Berzofsky, Jay A.] NCI, CCR, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD OCT 1
PY 2014
VL 74
IS 19
SU S
MA 3657
DI 10.1158/1538-7445.AM2014-3657
PG 1
WC Oncology
SC Oncology
GA CB8VR
UT WOS:000349910201149
ER
PT J
AU Janakiram, NB
Mohammed, A
Brewer, M
Collin, PD
Steele, VE
Rao, CV
AF Janakiram, Naveena B.
Mohammed, Altaf
Brewer, Misty
Collin, Peter D.
Steele, Vernon E.
Rao, Chinthalapally V.
TI Chemopreventive and immune-modulatory effects of the Cucumaria frondosa
extract, Frondanol A5 in the APCMin/ plus mice intestinal tumorigenesis
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 105th Annual Meeting of the American-Association-for-Cancer-Research
(AACR)
CY APR 05-09, 2014
CL San Diego, CA
SP Amer Assoc Canc Res
C1 [Janakiram, Naveena B.; Mohammed, Altaf; Brewer, Misty; Rao, Chinthalapally V.] Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA.
[Collin, Peter D.] Coastside Bio Resources, Deer Isle, ME USA.
[Steele, Vernon E.] NCI, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD OCT 1
PY 2014
VL 74
IS 19
SU S
MA 2145
DI 10.1158/1538-7445.AM2014-2145
PG 2
WC Oncology
SC Oncology
GA CB8UN
UT WOS:000349906902357
ER
PT J
AU Jawale, RM
Williams, K
Lee, M
Yang, HH
Figueroa, J
Sherman, M
Otis, CN
Arcaro, K
AF Jawale, Rahul M.
Williams, Krisitin
Lee, Maxwell
Yang, Howard H.
Figueroa, Jonine
Sherman, Mark
Otis, Christopher N.
Arcaro, Kathleen
TI Tamoxifen-resistant breast cancer: DNA methylation and expression of
MAGED1
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 105th Annual Meeting of the American-Association-for-Cancer-Research
(AACR)
CY APR 05-09, 2014
CL San Diego, CA
SP Amer Assoc Canc Res
C1 [Jawale, Rahul M.; Otis, Christopher N.] Baystate Med Ctr, Springfield, MA USA.
[Williams, Krisitin; Arcaro, Kathleen] Univ Massachusetts, Amherst, MA 01003 USA.
[Lee, Maxwell; Yang, Howard H.; Figueroa, Jonine; Sherman, Mark] NCI, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 3
U2 3
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD OCT 1
PY 2014
VL 74
IS 19
SU S
MA 385
DI 10.1158/1538-7445.AM2014-385
PG 2
WC Oncology
SC Oncology
GA CB8UN
UT WOS:000349906904352
ER
PT J
AU Jessop, L
Bigot, P
Machiela, M
Myers, T
Sikdar, N
Colli, L
Chanock, S
AF Jessop, Lea
Bigot, Pierre
Machiela, Mitchell
Myers, Timothy
Sikdar, Nilabja
Colli, Leandro
Chanock, Stephen
TI Post-GWAS functional characterization of the 12p11.23 renal cancer
susceptibility locus implicates BHLHE41
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 105th Annual Meeting of the American-Association-for-Cancer-Research
(AACR)
CY APR 05-09, 2014
CL San Diego, CA
SP Amer Assoc Canc Res
C1 [Jessop, Lea; Bigot, Pierre; Machiela, Mitchell; Myers, Timothy; Sikdar, Nilabja; Colli, Leandro; Chanock, Stephen] NCI, Gaithersburg, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD OCT 1
PY 2014
VL 74
IS 19
SU S
MA 5061
DI 10.1158/1538-7445.AM2014-5061
PG 1
WC Oncology
SC Oncology
GA CB8VR
UT WOS:000349910204016
ER
PT J
AU Jiang, Q
Xiao, ZX
Back, T
Scarzello, A
Roan, S
Willette-Brown, J
Zhu, F
Hu, YL
Wiltrout, RH
AF Jiang, Qun
Xiao, Zuoxiang
Back, Timothy
Scarzello, Anthony
Roan, Scott
Willette-Brown, Jami
Zhu, Feng
Hu, Yinling
Wiltrout, Robert H.
TI Ikk alpha modulates primary sclerosing cholangitis and intrahepatic
cholangiocarcinoma
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 105th Annual Meeting of the American-Association-for-Cancer-Research
(AACR)
CY APR 05-09, 2014
CL San Diego, CA
SP Amer Assoc Canc Res
C1 [Jiang, Qun; Xiao, Zuoxiang; Back, Timothy; Scarzello, Anthony; Roan, Scott; Willette-Brown, Jami; Zhu, Feng; Hu, Yinling; Wiltrout, Robert H.] NCI Frederick, Frederick, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD OCT 1
PY 2014
VL 74
IS 19
SU S
MA 3618
DI 10.1158/1538-7445.AM2014-3618
PG 1
WC Oncology
SC Oncology
GA CB8VR
UT WOS:000349910201113
ER
PT J
AU Jochems, C
Boyerinas, B
Madan, RA
Poole, DJ
Ning, YM
Figg, WD
Liewehr, DJ
Steinberg, SM
Gulley, JL
Tsang, KY
Schlom, J
AF Jochems, Caroline
Boyerinas, Benjamin
Madan, Ravi A.
Poole, Diane J.
Ning, Yang-Min
Figg, William D.
Liewehr, David J.
Steinberg, Seth M.
Gulley, James L.
Tsang, Kwong-Yok
Schlom, Jeffrey
TI Analysis of immune cell subsets in a multidrug therapeutic regimen for
patients with metastatic castration-resistant prostate cancer
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 105th Annual Meeting of the American-Association-for-Cancer-Research
(AACR)
CY APR 05-09, 2014
CL San Diego, CA
SP Amer Assoc Canc Res
C1 [Jochems, Caroline; Boyerinas, Benjamin; Madan, Ravi A.; Poole, Diane J.; Figg, William D.; Liewehr, David J.; Steinberg, Seth M.; Gulley, James L.; Tsang, Kwong-Yok; Schlom, Jeffrey] NCI, Bethesda, MD 20892 USA.
[Ning, Yang-Min] US FDA, Bethesda, MD 20014 USA.
RI Gulley, James/K-4139-2016; Figg Sr, William/M-2411-2016
OI Gulley, James/0000-0002-6569-2912;
NR 0
TC 0
Z9 0
U1 0
U2 2
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD OCT 1
PY 2014
VL 74
IS 19
SU S
MA 2546
DI 10.1158/1538-7445.AM2014-2546
PG 1
WC Oncology
SC Oncology
GA CB8UN
UT WOS:000349906903284
ER
PT J
AU Jones, GC
Mitchell, JB
Johnson, BE
Camphausen, K
Glatstein, E
Simone, CB
AF Jones, Guy C.
Mitchell, James B.
Johnson, Bruce E.
Camphausen, Kevin
Glatstein, Eli
Simone, Charles B.
TI Phase II study of low-dose rate thoracic radiotherapy for treatment of
intrathoracic relapsed or progressive small cell lung cancer
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 105th Annual Meeting of the American-Association-for-Cancer-Research
(AACR)
CY APR 05-09, 2014
CL San Diego, CA
SP Amer Assoc Canc Res
C1 [Jones, Guy C.; Mitchell, James B.; Camphausen, Kevin] Natl Canc Inst, Bethesda, MD USA.
[Johnson, Bruce E.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Glatstein, Eli; Simone, Charles B.] Univ Penn, Philadelphia, PA 19104 USA.
NR 0
TC 0
Z9 0
U1 1
U2 2
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD OCT 1
PY 2014
VL 74
IS 19
SU S
MA CT343
DI 10.1158/1538-7445.AM2014-CT343
PG 1
WC Oncology
SC Oncology
GA CB8VR
UT WOS:000349910205107
ER
PT J
AU Josse, R
Martin, SE
Guha, R
Ormanoglu, P
Pfister, T
Morris, J
Doroshow, JH
Pommier, Y
AF Josse, Rozenn
Martin, Scott E.
Guha, Rajarshi
Ormanoglu, Pinar
Pfister, Thomas
Morris, Joel
Doroshow, James H.
Pommier, Yves
TI The ATR inhibitor VE-821 in combination with the novel topoisomerase I
inhibitor LMP-400 selectively kills cancer cells by disabling DNA
replication initiation and fork elongation
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 105th Annual Meeting of the American-Association-for-Cancer-Research
(AACR)
CY APR 05-09, 2014
CL San Diego, CA
SP Amer Assoc Canc Res
C1 [Josse, Rozenn; Pommier, Yves] NCI, Mol Pharmacol Lab, CCR, Bethesda, MD 20892 USA.
[Martin, Scott E.; Guha, Rajarshi; Ormanoglu, Pinar] NCATS, Div Preclin Innovat, Rockville, MD USA.
[Pfister, Thomas; Morris, Joel; Doroshow, James H.] NCI, Drug Synth & Chem Branch, Div Canc Treatment, Div Canc Treatment & Diag DTP DCTD, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD OCT 1
PY 2014
VL 74
IS 19
SU S
MA 794
DI 10.1158/1538-7445.AM2014-794
PG 1
WC Oncology
SC Oncology
GA CB8UN
UT WOS:000349906905254
ER
PT J
AU Kales, SC
Ryan, PE
Nau, MM
Green, JE
Lipkowitz, S
AF Kales, Stephen C.
Ryan, Philip E.
Nau, Marion M.
Green, Jeffrey E.
Lipkowitz, Stanley
TI Loss of function Cbl-c mutations in solid tumors
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 105th Annual Meeting of the American-Association-for-Cancer-Research
(AACR)
CY APR 05-09, 2014
CL San Diego, CA
SP Amer Assoc Canc Res
C1 [Kales, Stephen C.; Ryan, Philip E.; Nau, Marion M.; Green, Jeffrey E.; Lipkowitz, Stanley] NCI, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD OCT 1
PY 2014
VL 74
IS 19
SU S
MA 4429
DI 10.1158/1538-7445.AM2014-4429
PG 1
WC Oncology
SC Oncology
GA CB8VR
UT WOS:000349910202403
ER
PT J
AU Kang, ZG
Yu, YK
Cao, L
Meltzer, PS
Zhu, YL
Shah, A
Gulley, J
Duht, W
Madan, R
Bhagat, A
Zhao, KR
AF Kang, Zhigang
Yu, Yunkai
Cao, Liang
Meltzer, Paul S.
Zhu, Yuelin
Shah, Avan
Gulley, James
Duht, William
Madan, Ravi
Bhagat, Ali
Zhao, Kyra
TI A novel AR splice variant identified in circulating tumor cells from
castration-resistant prostate cancer patient blood as a potentially
prognostic biomarker
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 105th Annual Meeting of the American-Association-for-Cancer-Research
(AACR)
CY APR 05-09, 2014
CL San Diego, CA
SP Amer Assoc Canc Res
C1 [Kang, Zhigang; Yu, Yunkai; Cao, Liang; Meltzer, Paul S.; Zhu, Yuelin; Shah, Avan; Gulley, James; Duht, William; Madan, Ravi] NCI, Bethesda, MD 20892 USA.
[Bhagat, Ali; Zhao, Kyra] Clearbridge BioMed, Singapore, Singapore.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD OCT 1
PY 2014
VL 74
IS 19
SU S
MA 4815
DI 10.1158/1538-7445.AM2014-4815
PG 2
WC Oncology
SC Oncology
GA CB8VR
UT WOS:000349910203285
ER
PT J
AU Kang, ZG
Yu, YK
Zhu, YLJ
Helman, L
Meltzer, P
Cao, L
AF Kang, Zhigang
Yu, Yunkai
Zhu, Yuelin J.
Helman, Lee
Meltzer, Paul
Cao, Liang
TI Down-regulation of IGFBP2 is associated with resistance to IGF1R therapy
in rhabdomyosarcoma
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 105th Annual Meeting of the American-Association-for-Cancer-Research
(AACR)
CY APR 05-09, 2014
CL San Diego, CA
SP Amer Assoc Canc Res
C1 [Kang, Zhigang; Yu, Yunkai; Zhu, Yuelin J.; Helman, Lee; Meltzer, Paul; Cao, Liang] NCI, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD OCT 1
PY 2014
VL 74
IS 19
SU S
MA 1719
DI 10.1158/1538-7445.AM2014-1719
PG 1
WC Oncology
SC Oncology
GA CB8UN
UT WOS:000349906901441
ER
PT J
AU Kato, JR
Bu, XN
Moss, J
AF Kato, Jiro
Bu, Xiangning
Moss, Joel
TI Estrogen promotes tumorigenesis by ADP-ribosyl-acceptor hydrolase 1
(ARH1)-deficient cells and mice
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 105th Annual Meeting of the American-Association-for-Cancer-Research
(AACR)
CY APR 05-09, 2014
CL San Diego, CA
SP Amer Assoc Canc Res
C1 [Kato, Jiro; Bu, Xiangning; Moss, Joel] NHLBI, NIH, Bethesda, MD 20892 USA.
RI bu, xiangning/N-4343-2015
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD OCT 1
PY 2014
VL 74
IS 19
SU S
MA 2445
DI 10.1158/1538-7445.AM2014-2445
PG 1
WC Oncology
SC Oncology
GA CB8UN
UT WOS:000349906903174
ER
EF